FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Han, M
Lee, C
Park, S
Baek, J
AF Han, Minah
Lee, Changwoo
Park, Subok
Baek, Jongduk
TI Investigation on slice direction dependent detectability of volumetric
cone beam CT images
SO OPTICS EXPRESS
LA English
DT Article
ID CHANNELIZED HOTELLING OBSERVER; DISTRIBUTED LUMPY BACKGROUNDS;
COMPUTED-TOMOGRAPHY SYSTEM; SPECT MAP RECONSTRUCTION; NOISE POWER
SPECTRUM; LESION SIZE; MODEL OBSERVERS; DETECTION TASKS; OBJECT
VARIABILITY; GAUSSIAN SIGNAL
AB We investigate the detection performance of transverse and longitudinal planes for various signal sizes (i.e., 1 mm to 8 mm diameter spheres) in cone beam computed tomography (CBCT) images. CBCT images are generated by computer simulation and images are reconstructed using an FDK algorithm. For each slice direction and signal size, a human observer study is conducted with a signal-known-exactly/background-known-exactly (SKE/BKE) binary detection task. The detection performance of human observers is compared with that of a channelized Hotelling observer (CHO). The detection performance of an ideal linear observer is also calculated using a CHO with Laguerre-Gauss (LG) channels. The detectability of high contrast small signals (i.e., up to 4-mm-diameter spheres) is higher in the longitudinal plane than the transverse plane. It is also shown that CHO performance correlates well with human observer performance in both transverse and longitudinal plane images. (C) 2016 Optical Society of America
C1 [Han, Minah; Lee, Changwoo; Baek, Jongduk] Yonsei Univ, Sch Integrated Technol, Inchon, South Korea.
[Han, Minah; Lee, Changwoo; Baek, Jongduk] Yonsei Univ, Yonsei Inst Convergence Technol, Inchon, South Korea.
[Park, Subok] US FDA, Silver Spring, MD USA.
RP Baek, J (reprint author), Yonsei Univ, Sch Integrated Technol, Inchon, South Korea.; Baek, J (reprint author), Yonsei Univ, Yonsei Inst Convergence Technol, Inchon, South Korea.
EM jongdukbaek@yonsei.ac.kr
FU MSIP (Ministry of Science, ICT and Future Planning), Korea, under the IT
Consilience Creative Programs [IITP-2015-R0346-15-1008]; Basic Science
Research Program through the National Research Foundation of Korea (NRF)
- Ministry of Science, ICT & Future Planning [2015R1C1A1A01052268];
National Research Foundation of Korea [NRF-2015K2A1A2067635]
FX This research was supported by the MSIP (Ministry of Science, ICT and
Future Planning), Korea, under the IT Consilience Creative Programs
(IITP-2015-R0346-15-1008) supervised by the IITP (Institute for
Information& Communications Technology Promotion), Basic Science
Research Program through the National Research Foundation of Korea (NRF)
funded by the Ministry of Science, ICT & Future Planning
(2015R1C1A1A01052268) and the framework of international cooperation
program managed by National Research Foundation of Korea
(NRF-2015K2A1A2067635).
NR 59
TC 1
Z9 1
U1 1
U2 1
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 1094-4087
J9 OPT EXPRESS
JI Opt. Express
PD FEB 22
PY 2016
VL 24
IS 4
BP 3749
EP 3764
DI 10.1364/OE.24.003749
PG 16
WC Optics
SC Optics
GA DF5ZQ
UT WOS:000371433700054
PM 26907031
ER
PT J
AU Tolstorukov, MY
Virnik, K
Zhurkin, VB
Adhya, S
AF Tolstorukov, Michael Y.
Virnik, Konstantin
Zhurkin, Victor B.
Adhya, Sankar
TI Organization of DNA in a bacterial nucleoid
SO BMC MICROBIOLOGY
LA English
DT Article
DE Bacterial; Nucleoid; MNase; Digestion; Sequencing; Genomic; DNA;
Packaging; Structural; Organization
ID ESCHERICHIA-COLI CHROMOSOME; SEQUENCE-DIRECTED CURVATURE; PROKARYOTIC
DNA; GENE-EXPRESSION; MICROCOCCAL NUCLEASE; ELECTRON-MICROSCOPY; FOLDED
CHROMOSOMES; BINDING PROTEINS; CHIP-SEQ; H-NS
AB Background: It is unclear how DNA is packaged in a bacterial cell in the absence of nucleosomes. To investigate the initial level of DNA condensation in bacterial nucleoid we used in vivo DNA digestion coupled with high-throughput sequencing of the digestion-resistant fragments. To this end, we transformed E. coli cells with a plasmid expressing micrococcal nuclease. The nuclease expression was under the control of AraC repressor, which enabled us to perform an inducible digestion of bacterial nucleoid inside a living cell.
Results: Analysis of the genomic localization of the digestion-resistant fragments revealed their non-random distribution. The patterns observed in the distribution of the sequenced fragments indicate the presence of short DNA segments protected from the enzyme digestion, possibly because of interaction with DNA-binding proteins. The average length of such digestion-resistant segments is about 50 bp and the characteristic repeat in their distribution is about 90 bp. The gene starts are depleted of the digestion-resistant fragments, suggesting that these genomic regions are more exposed than genomic sequences on average. Sequence analysis of the digestion-resistant segments showed that while the GC-content of such sequences is close to the genome-wide value, they are depleted of A-tracts as compared to the bulk genomic DNA or to the randomized sequence of the same nucleotide composition.
Conclusions: Our results suggest that DNA is packaged in the bacterial nucleoid in a non-random way that facilitates interaction of the DNA binding factors with regulatory regions of the genome.
C1 [Tolstorukov, Michael Y.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Tolstorukov, Michael Y.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Virnik, Konstantin] FDA, Ctr Biol, Off Vaccines, Lab Immunoregulat,Div Viral Prod, Silver Spring, MD 20993 USA.
[Zhurkin, Victor B.] NCI, Lab Cell Biol, NIH, Bethesda, MD 20892 USA.
[Adhya, Sankar] NCI, Lab Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Adhya, S (reprint author), NCI, Lab Mol Biol, NIH, Bethesda, MD 20892 USA.
EM adhyas@mail.nih.gov
NR 77
TC 1
Z9 1
U1 4
U2 13
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2180
J9 BMC MICROBIOL
JI BMC Microbiol.
PD FEB 20
PY 2016
VL 16
AR 22
DI 10.1186/s12866-016-0637-3
PG 11
WC Microbiology
SC Microbiology
GA DE2RK
UT WOS:000370474300001
PM 26897370
ER
PT J
AU Trbojevich, RA
Fernandez, A
Watanabe, F
Mustafa, T
Bryant, MS
AF Trbojevich, Raul A.
Fernandez, Avelina
Watanabe, Fumiya
Mustafa, Thikra
Bryant, Matthew S.
TI Comparative study of silver nanoparticle permeation using Side-Bi-Side
and Franz diffusion cells
SO JOURNAL OF NANOPARTICLE RESEARCH
LA English
DT Article
DE Membranes; Silver nanoparticles; Diffusion cells; Food packaging;
Permeation; Environmental and health effects
ID FOOD CONTAINERS; FILMS; NANOTECHNOLOGY; NANOCOMPOSITES; MIGRATION;
RELEASE
AB Better understanding the mechanisms of nanoparticle permeation through membranes and packaging polymers has important implications for the evaluation of drug transdermal uptake, in food safety and the environmental implications of nanotechnology. In this study, permeation of 21 nm diameter silver nanoparticles (AgNPs) was tested using Side-Bi-Side and Franz static diffusion cells through hydrophilic 0.1 and 0.05 lm pore diameter 125 mu m thick synthetic cellulose membranes, and 16 and 120 mu m thick low-density polyethylene (LDPE) films. Experiments performed with LDPE films discarded permeation of AgNPs or Ag ions over the investigated time-frame in both diffusion systems. But controlled release of AgNPs has been quantified using semipermeable hydrophilic membranes. The permeation followed a quasi-linear time-dependent model during the experimental time-frame, which represents surface reaction-limited permeation. Diffusive flux, diffusion coefficients, and membrane permeability were determined as a function of pore size and diffusion model. Concentration gradient and pore size were key to understand mass transfer phenomena in the diffusion systems.
C1 [Trbojevich, Raul A.; Bryant, Matthew S.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
[Fernandez, Avelina] Univ Valencia, Consejo Super Invest Cient, Inst Fis Corpuscular, Parc Cient, Valencia 46980, Spain.
[Watanabe, Fumiya; Mustafa, Thikra] Univ Arkansas Little Rock, Ctr Integrat Nanotechnol Sci, 2801 S Univ Ave, Little Rock, AR 72204 USA.
[Mustafa, Thikra] Univ Baghdad, Coll Sci Women, Dept Biol, Baghdad, Iraq.
RP Fernandez, A (reprint author), Univ Valencia, Consejo Super Invest Cient, Inst Fis Corpuscular, Parc Cient, Valencia 46980, Spain.
EM velifdez@ific.uv.es
FU Division of Biochemical Toxicology, from National Center for
Toxicological Research [E073680]; U.S. Food and Drug Administration
FX This study was supported through the project # E073680, Division of
Biochemical Toxicology, from National Center for Toxicological Research,
and U.S. Food and Drug Administration. We gratefully acknowledge
assistance of the FDA NCTR/ORA Nanotechnology Core Facility, Jefferson,
Arkansas, in which part of this study was conducted. The authors thank
Dr. Frederick Beland and Dr. Paul Howard for assistance in the review of
this manuscript.
NR 25
TC 0
Z9 0
U1 4
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1388-0764
EI 1572-896X
J9 J NANOPART RES
JI J. Nanopart. Res.
PD FEB 19
PY 2016
VL 18
IS 3
AR 55
DI 10.1007/s11051-016-3363-8
PG 12
WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials
Science, Multidisciplinary
SC Chemistry; Science & Technology - Other Topics; Materials Science
GA EB0OV
UT WOS:000387044400002
ER
PT J
AU Su, JR
Miller, ER
Duffy, J
Baer, BM
Cano, MV
AF Su, John R.
Miller, Elaine R.
Duffy, Jonathan
Baer, Bethany M.
Cano, Maria V.
TI Administration Error Involving a Meningococcal Conjugate Vaccine -
United States, March 1, 2010-September 22, 2015
SO MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT
LA English
DT Article
C1 [Su, John R.; Miller, Elaine R.; Duffy, Jonathan; Cano, Maria V.] CDC, Div Healthcare Qual Promot, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA.
[Baer, Bethany M.] Food & Drug Adm, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, San Diego, CA USA.
RP Su, JR (reprint author), CDC, Div Healthcare Qual Promot, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA.
EM ezu2@cdc.gov
NR 5
TC 1
Z9 1
U1 1
U2 1
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 0149-2195
EI 1545-861X
J9 MMWR-MORBID MORTAL W
JI MMWR-Morb. Mortal. Wkly. Rep.
PD FEB 19
PY 2016
VL 65
IS 6
BP 161
EP 162
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DF4TY
UT WOS:000371345000006
PM 26890604
ER
PT J
AU Meseda, CA
Atukorale, V
Kuhn, J
Schmeisser, F
Weir, JP
AF Meseda, Clement A.
Atukorale, Vajini
Kuhn, Jordan
Schmeisser, Falko
Weir, Jerry P.
TI Percutaneous Vaccination as an Effective Method of Delivery of MVA and
MVA-Vectored Vaccines
SO PLOS ONE
LA English
DT Article
ID PHASE-I TRIAL; VIRUS-ANKARA; SMALLPOX VACCINE; INFLUENZA-VIRUS;
CLINICAL-TRIAL; HEALTHY-ADULTS; MICRONEEDLE ARRAYS; SKIN VACCINATION;
ANTIGEN DELIVERY; IMMUNE-RESPONSES
AB The robustness of immune responses to an antigen could be dictated by the route of vaccine inoculation. Traditional smallpox vaccines, essentially vaccinia virus strains, that were used in the eradication of smallpox were administered by percutaneous inoculation (skin scarification). The modified vaccinia virus Ankara is licensed as a smallpox vaccine in Europe and Canada and currently undergoing clinical development in the United States. MVA is also being investigated as a vector for the delivery of heterologous genes for prophylactic or therapeutic immunization. Since MVA is replication-deficient, MVA and MVA-vectored vaccines are often inoculated through the intramuscular, intradermal or subcutaneous routes. Vaccine inoculation via the intramuscular, intradermal or subcutaneous routes requires the use of injection needles, and an estimated 10 to 20% of the population of the United States has needle phobia. Following an observation in our laboratory that a replication-deficient recombinant vaccinia virus derived from the New York City Board of Health strain elicited protective immune responses in a mouse model upon inoculation by tail scarification, we investigated whether MVA and MVA recombinants can elicit protective responses following percutaneous administration in mouse models. Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. High titers of specific neutralizing antibodies were elicited in mice inoculated with a recombinant MVA expressing the herpes simplex type 2 glycoprotein D after scarification. Similarly, a recombinant MVA expressing the hemagglutinin of attenuated influenza virus rgA/Viet Nam/1203/2004 (H5N1) elicited protective immune responses when administered at low doses by scarification. Taken together, our data suggest that MVA and MVA-vectored vaccines inoculated by scarification can elicit protective immune responses that are comparable to subcutaneous vaccination, and may allow for antigen sparing when vaccine supply is limited.
C1 [Meseda, Clement A.; Atukorale, Vajini; Kuhn, Jordan; Schmeisser, Falko; Weir, Jerry P.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
RP Meseda, CA (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM Clement.Meseda@fda.hhs.gov
FU Center for Biologics Evaluation and Research, US Food and Drug
Administration; CBER/FDA
FX The work described in this manuscript was supported by intramural
research fund provided by the Center for Biologics Evaluation and
Research, US Food and Drug Administration.; The authors wish to thank
Drs. Bernard Moss and Linda Wyatt, NIAID/NIH, for the MVA and VV-WR
viruses. We also thank Dr. Maryna Eichelberger and Dr. Alonzo Garcia,
CBER/FDA, for reviewing this manuscript. This work was supported by
intramural research funds from CBER/FDA.
NR 89
TC 0
Z9 0
U1 4
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 19
PY 2016
VL 11
IS 2
AR e0149364
DI 10.1371/journal.pone.0149364
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF3DG
UT WOS:000371223400048
PM 26895072
ER
PT J
AU He, WW
Jia, HM
Cai, JH
Han, XN
Zheng, Z
Warner, WG
Yin, JJ
AF He, Weiwei
Jia, Huimin
Cai, Junhui
Han, Xiangna
Zheng, Zhi
Warner, Wayne G.
Yin, Jun-Jie
TI Production of Reactive Oxygen Species and Electrons from Photoexcited
ZnO and ZnS Nanoparticles: A Comparative Study for Unraveling their
Distinct Photocatalytic Activities
SO JOURNAL OF PHYSICAL CHEMISTRY C
LA English
DT Article
ID HYDROGEN-PEROXIDE; HYBRID NANOSTRUCTURES; OXIDE NANOPARTICLES;
CHARGE-CARRIERS; SINGLET OXYGEN; ZINC-OXIDE; GENERATION; DEGRADATION;
SUPEROXIDE; LIGHT
AB The photoactivity of semiconductor rianostructures makes them potentially useful for environmental remediation and antibacterial applications. Understanding the mechanism underlying the photochemical and photobiological activities of photoexcited semiconductors is of great importance for developing applications and assessing associated risks. In the current work, using electron spin resonance spectroscopy coupled with spin trapping and spin labeling techniques, we comparatively and systematically investigate the abilities of ZnO and ZnS to generate hydroxyl radical, superoxide, singlet oxygen, photoinduced electrons, and oxygen consumption during irradiation. It was found that although ZnO and ZnS, when photoexcited, can produce hydroxyl radical, superoxide, and singlet oxygen, ZnO is more effective than ZnS in producing hydroxyl radical and singlet oxygen while ZnS is more effective than ZnO in generating superoxide. The characterization with ESR spin labeling and oxirnetry indicates ZnS is about 4 times more active than ZnO in production of photoinduced electrons and consumption of oxygen. We compared the photocatalytic and antibacterial activities of ZnO and ZnS and found that ZnO exhibits efficient and broad photo catalytic and antibacterial activity, conversely, ZnS is only effective in photodegradation of RhB and killing Staphylococcus aureus. The distinct photocatalytic activities of ZnO and ZnS nanoparticles were attributable to their unique capability to facilitate the generation of reactive oxygen species and charge carriers during photoirradiation. These results provide valuable information, for understanding the photocatalytic mechanism of metal oxide and metal sulfides and for predicting their photocatalytic activities.
C1 [He, Weiwei; Jia, Huimin; Cai, Junhui; Han, Xiangna; Zheng, Zhi] Xuchang Univ, Inst Surface Micro & Nanomat, Key Lab Micronano Energy Storage & Convers Mat He, Xuchang 461000, Henan, Peoples R China.
[Warner, Wayne G.; Yin, Jun-Jie] US FDA, Div Bioanalyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Warner, Wayne G.; Yin, Jun-Jie] US FDA, Div Analyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
RP He, WW (reprint author), Xuchang Univ, Inst Surface Micro & Nanomat, Key Lab Micronano Energy Storage & Convers Mat He, Xuchang 461000, Henan, Peoples R China.; Yin, JJ (reprint author), US FDA, Div Bioanalyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.; Yin, JJ (reprint author), US FDA, Div Analyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
EM heweiweixcu@gmail.com; junjie.yin@fda.hhs.gov
RI Yin, Jun Jie /E-5619-2014; Zheng, Zhi/J-3198-2016
FU National Natural Science Foundation of China [21303153]; Program for
Science & Technology Innovation Talents in Universities of Henan
Province [14HASTIT008]; Innovation Scientists and Technicians Troop
Construction Projects of Henan Province [144200510014]
FX This work was supported by National Natural Science Foundation of China
(Grant No. 21303153), Program for Science & Technology Innovation
Talents in Universities of Henan Province (14HASTIT008), and Innovation
Scientists and Technicians Troop Construction Projects of Henan Province
(Grant No. 144200510014). This article is not an official US Food and
Drug Administration (FDA) guidance or policy statement. No official
support or endorsement by the US FDA is intended or should be inferred.
NR 34
TC 5
Z9 5
U1 12
U2 46
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1932-7447
J9 J PHYS CHEM C
JI J. Phys. Chem. C
PD FEB 18
PY 2016
VL 120
IS 6
BP 3187
EP 3195
DI 10.1021/acs.jpcc.5b11456
PG 9
WC Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science,
Multidisciplinary
SC Chemistry; Science & Technology - Other Topics; Materials Science
GA DE5NW
UT WOS:000370678700010
ER
PT J
AU Geller, AI
Mozersky, RP
Budnitz, DS
AF Geller, Andrew I.
Mozersky, Robert P.
Budnitz, Daniel S.
TI Emergency Department Visits Related to Dietary Supplements Reply
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Geller, Andrew I.; Budnitz, Daniel S.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Mozersky, Robert P.] Food & Drug Adm, College Pk, MD USA.
RP Geller, AI (reprint author), Ctr Dis Control & Prevent, Atlanta, GA USA.
EM ageller@cdc.gov
NR 1
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 18
PY 2016
VL 374
IS 7
BP 695
EP 695
DI 10.1056/NEJMc1514454
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA DD9ER
UT WOS:000370229000030
PM 26886539
ER
PT J
AU Horne, HN
Sherman, ME
Pfeiffer, RM
Figueroa, JD
Khodr, ZG
Falk, RT
Pollak, M
Patel, DA
Palakal, MM
Linville, L
Papathomas, D
Geller, B
Vacek, PM
Weaver, DL
Chicoine, R
Shepherd, J
Mahmoudzadeh, AP
Wang, J
Fan, B
Malkov, S
Herschorn, S
Hewitt, SM
Brinton, LA
Gierach, GL
AF Horne, Hisani N.
Sherman, Mark E.
Pfeiffer, Ruth M.
Figueroa, Jonine D.
Khodr, Zeina G.
Falk, Roni T.
Pollak, Michael
Patel, Deesha A.
Palakal, Maya M.
Linville, Laura
Papathomas, Daphne
Geller, Berta
Vacek, Pamela M.
Weaver, Donald L.
Chicoine, Rachael
Shepherd, John
Mahmoudzadeh, Amir Pasha
Wang, Jeff
Fan, Bo
Malkov, Serghei
Herschorn, Sally
Hewitt, Stephen M.
Brinton, Louise A.
Gierach, Gretchen L.
TI Circulating insulin-like growth factor-I, insulin-like growth factor
binding protein-3 and terminal duct lobular unit involution of the
breast: a cross-sectional study of women with benign breast disease
SO BREAST CANCER RESEARCH
LA English
DT Article
ID CANCER-RISK; MAMMOGRAPHIC DENSITY; IGF-I; POSTMENOPAUSAL WOMEN;
RACIAL-DIFFERENCES; MENSTRUAL-CYCLE; NURSES HEALTH; SEX-HORMONES;
ASSOCIATION; IGFBP-3
AB Background: Terminal duct lobular units (TDLUs) are the primary structures from which breast cancers and their precursors arise. Decreased age-related TDLU involution and elevated mammographic density are both correlated and independently associated with increased breast cancer risk, suggesting that these characteristics of breast parenchyma might be linked to a common factor. Given data suggesting that increased circulating levels of insulin-like growth factors (IGFs) factors are related to reduced TDLU involution and increased mammographic density, we assessed these relationships using validated quantitative methods in a cross-sectional study of women with benign breast disease.
Methods: Serum IGF-I, IGFBP-3 and IGF-I: IGFBP-3 molar ratios were measured in 228 women, ages 40-64, who underwent diagnostic breast biopsies yielding benign diagnoses at University of Vermont affiliated centers. Biopsies were assessed for three separate measures inversely related to TDLU involution: numbers of TDLUs per unit of tissue area ("TDLU count"), median TDLU diameter ("TDLU span"), and number of acini per TDLU ("acini count"). Regression models, stratified by menopausal status and adjusted for potential confounders, were used to assess the associations of TDLU count, median TDLU span and median acini count per TDLU with tertiles of circulating IGFs. Given that mammographic density is associated with both IGF levels and breast cancer risk, we also stratified these associations by mammographic density.
Results: Higher IGF-I levels among postmenopausal women and an elevated IGF-I: IGFBP-3 ratio among all women were associated with higher TDLU counts, a marker of decreased lobular involution (P-trend = 0.009 and <0.0001, respectively); these associations were strongest among women with elevated mammographic density (P-interaction <0.01). Circulating IGF levels were not significantly associated with TDLU span or acini count per TDLU.
Conclusions: These results suggest that elevated IGF levels may define a sub-group of women with high mammographic density and limited TDLU involution, two markers that have been related to increased breast cancer risk. If confirmed in prospective studies with cancer endpoints, these data may suggest that evaluation of IGF signaling and its downstream effects may have value for risk prediction and suggest strategies for breast cancer chemoprevention through inhibition of the IGF system.
C1 [Horne, Hisani N.; Khodr, Zeina G.; Falk, Roni T.; Patel, Deesha A.; Palakal, Maya M.; Linville, Laura; Papathomas, Daphne; Gierach, Gretchen L.] NCI, Metabol Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Rm 7-E108, Bethesda, MD 20892 USA.
[Horne, Hisani N.] US FDA, Silver Spring, MD USA.
[Sherman, Mark E.] NCI, Breast & Gynecol Canc Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Figueroa, Jonine D.] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
[Pollak, Michael] McGill Univ, Montreal, PQ, Canada.
[Patel, Deesha A.] Northwestern Univ, Sch Med, Chicago, IL 60611 USA.
[Geller, Berta; Vacek, Pamela M.; Weaver, Donald L.; Chicoine, Rachael] Univ Vermont, Burlington, VT USA.
[Shepherd, John; Mahmoudzadeh, Amir Pasha; Fan, Bo; Malkov, Serghei; Herschorn, Sally] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
[Wang, Jeff] Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido, Japan.
[Hewitt, Stephen M.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Brinton, Louise A.] NCI, Off Director, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Gierach, GL (reprint author), NCI, Metabol Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Rm 7-E108, Bethesda, MD 20892 USA.
EM gierachg@mail.nih.gov
RI Gierach, Gretchen/E-1817-2016;
OI Gierach, Gretchen/0000-0002-0165-5522; Hewitt,
Stephen/0000-0001-8283-1788
FU Intramural Research Program of the NIH, National Cancer Institute;
National Cancer Institute [U01CA70013, 1R21CA157254]; National Center
for Research Resources [M01 RR000109]; Breast Cancer Research Stamp
Funds
FX The authors are indebted to the participants in the BREAST Stamp Project
for their outstanding cooperation and to the physicians, pathologists,
nurses, technologists, and interviewers for their efforts in the field.
The authors thank Claire Bove, Patricia Lutton, Ellen Young and Aileen
Burke for research assistance. We also thank Janet Lawler-Heaver and
Kerry Grace Morrissey from Westat for study management support and Jane
Demuth at Information Management Services for data support and analysis.
The authors would also like to thank Patricia Madigan for her editorial
assistance. This research was supported in part by the Intramural
Research Program of the NIH, National Cancer Institute and Breast Cancer
Research Stamp Funds. Cooperative agreement U01CA70013 (BM Geller, PM
Vacek, DL Weaver, RE Chicoine, SD Herschorn) and 1R21CA157254 (JA
Shepherd, B Fan, AP Mahmoudzadeh, S Malkov) from the National Cancer
Institute funded some of the data collection and image analysis for this
study. Grant number M01 RR000109 from the National Center for Research
Resources funded the blood processing at the University of Vermont
General Clinical Research Center.
NR 49
TC 3
Z9 3
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1465-542X
EI 1465-5411
J9 BREAST CANCER RES
JI Breast Cancer Res.
PD FEB 18
PY 2016
VL 18
AR 24
DI 10.1186/s13058-016-0678-4
PG 12
WC Oncology
SC Oncology
GA DE0NL
UT WOS:000370321500001
PM 26893016
ER
PT J
AU Fleming, IMC
Paris, Z
Gaston, KW
Balakrishnan, R
Fredrick, K
Rubio, MAT
Alfonzo, JD
AF Fleming, Ian M. C.
Paris, Zdenek
Gaston, Kirk W.
Balakrishnan, R.
Fredrick, Kurt
Rubio, Mary Anne T.
Alfonzo, Juan D.
TI A tRNA methyltransferase paralog is important for ribosome stability and
cell division in Trypanosoma brucei
SO SCIENTIFIC REPORTS
LA English
DT Article
ID BOWEN-CONRADI SYNDROME; SACCHAROMYCES-CEREVISIAE; AFRICAN TRYPANOSOMES;
PROTOZOAN PARASITES; BIOGENESIS REQUIRES; EUGLENA-GRACILIS; BINDING
PROTEIN; ASSEMBLY FACTOR; SUBUNIT; INTERFERENCE
AB Most eukaryotic ribosomes contain 26/28S, 5S, and 5.8S large subunit ribosomal RNAs (LSU rRNAs) in addition to the 18S rRNA of the small subunit (SSU rRNA). However, in kinetoplastids, a group of organisms that include medically important members of the genus Trypanosoma and Leishmania, the 26/28S large subunit ribosomal RNA is uniquely composed of 6 rRNA fragments. In addition, recent studies have shown the presence of expansion segments in the large ribosomal subunit (60S) of Trypanosoma brucei. Given these differences in structure, processing and assembly, T. brucei ribosomes may require biogenesis factors not found in other organisms. Here, we show that one of two putative 3-methylcytidine methyltransferases, TbMTase37 (a homolog of human methyltransferase- like 6, METTL6), is important for ribosome stability in T. brucei. TbMTase37 localizes to the nucleolus and depletion of the protein results in accumulation of ribosomal particles lacking srRNA 4 and reduced levels of polysome associated ribosomes. We also find that TbMTase37 plays a role in cytokinesis, as loss of the protein leads to multi-flagellated and multi-nucleated cells.
C1 [Fleming, Ian M. C.; Paris, Zdenek; Balakrishnan, R.; Fredrick, Kurt; Rubio, Mary Anne T.; Alfonzo, Juan D.] Ohio State Univ, Dept Microbiol, 484 W 12th Ave, Columbus, OH 43210 USA.
[Fleming, Ian M. C.; Paris, Zdenek; Balakrishnan, R.; Fredrick, Kurt; Rubio, Mary Anne T.; Alfonzo, Juan D.] Ohio State Univ, Ctr RNA Biol, Columbus, OH 43210 USA.
[Gaston, Kirk W.; Balakrishnan, R.] Univ Cincinnati, Dept Chem, Rieveschl Labs Mass Spectrometry, Cincinnati, OH 45221 USA.
[Fredrick, Kurt; Alfonzo, Juan D.] Ohio State Univ, Ohio State Biochem Program, Columbus, OH 43210 USA.
[Paris, Zdenek] Univ South Bohemia, Inst Parasitol, Ctr Biol, Ceske Budejovice 37005, Budweis, Czech Republic.
[Paris, Zdenek] Univ South Bohemia, Fac Sci, Ceske Budejovice 37005, Budweis, Czech Republic.
[Gaston, Kirk W.] US FDA, Cincinnati, OH USA.
RP Alfonzo, JD (reprint author), Ohio State Univ, Dept Microbiol, 484 W 12th Ave, Columbus, OH 43210 USA.; Alfonzo, JD (reprint author), Ohio State Univ, Ctr RNA Biol, Columbus, OH 43210 USA.; Alfonzo, JD (reprint author), Ohio State Univ, Ohio State Biochem Program, Columbus, OH 43210 USA.
EM alfonzo.1@osu.edu
RI Paris, Zdenek/G-7349-2014
FU Czech Grant Agency [15-21450Y]; NIH [R01 GM084065-07, R01 GM072528];
NIH-NIGMS [T32-GM086252]
FX We wish to thank M. Parsons for anti-Nog1 and all members of the Alfonzo
laboratory for valuable discussion and insights. This work was supported
by a Czech Grant Agency 15-21450Y grant to Z.P., NIH Grant R01
GM084065-07 to J.D.A. NIH-NIGMS Grant T32-GM086252 to I.M.C.F. and NIH
grant R01 GM072528 to K. F.
NR 44
TC 3
Z9 3
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD FEB 18
PY 2016
VL 6
AR 21438
DI 10.1038/srep21438
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE0WX
UT WOS:000370347400001
PM 26888608
ER
PT J
AU Zhang, L
Luo, S
Zhang, BL
AF Zhang, Lei
Luo, Shen
Zhang, Baolin
TI Glycan analysis of therapeutic glycoproteins
SO MABS
LA English
DT Review
DE lectin microarray; Analytics; glycosylation; biopharmaceuticals;
monoclonal antibodies; therapeutic proteins; glycan profiling
ID ELECTROPHORESIS-MASS SPECTROMETRY; PROTEIN GLYCOSYLATION ANALYSIS;
ANION-EXCHANGE CHROMATOGRAPHY; N-LINKED GLYCANS; INDUCED FLUORESCENCE
DETECTION; CAPILLARY GEL-ELECTROPHORESIS; PULSED AMPEROMETRIC DETECTION;
ASSISTED LECTIN MICROARRAY; MONOCLONAL-ANTIBODY; LIQUID-CHROMATOGRAPHY
AB Therapeutic monoclonal antibodies (mAbs) are glycoproteins produced by living cell systems. The glycan moieties attached to the proteins can directly affect protein stability, bioactivity, and immunogenicity. Therefore, glycan variants of a glycoprotein product must be adequately analyzed and controlled to ensure product quality. However, the inherent complexity of protein glycosylation poses a daunting analytical challenge. This review provides an update of recent advances in glycan analysis, including the potential utility of lectin-based microarray for high throughput glycan profiling. Emphasis is placed on comparison of the major types of analytics for use in determining unique glycan features such as glycosylation site, glycan structure, and content.
C1 [Zhang, Lei; Luo, Shen; Zhang, Baolin] US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Zhang, BL (reprint author), US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
EM Baolin.zhang@fda.hhs.gov
RI Zhang, Lei/F-5171-2010
FU Intramural FDA HHS [FD999999]
NR 115
TC 1
Z9 2
U1 10
U2 24
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1942-0862
EI 1942-0870
J9 MABS-AUSTIN
JI mAbs
PD FEB 17
PY 2016
VL 8
IS 2
BP 205
EP 215
DI 10.1080/19420862.2015.1117719
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DF4TZ
UT WOS:000371345100002
PM 26599345
ER
PT J
AU Fu, X
Wang, Z
Bhirde, A
Zhu, J
Liao, HS
Carvajal, N
Niu, G
Eden, H
Chen, XY
Jin, AJ
AF Fu, Xiao
Wang, Zhe
Bhirde, Ashwin
Zhu, Jenny
Liao, Hsien-Shun
Carvajal, Nicole
Niu, Gang
Eden, Henry
Chen, Xiaoyuan
Jin, Albert J.
TI Bio-AFM of Cancer Cells and Multifunctional Theranostics
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Fu, Xiao; Wang, Zhe; Bhirde, Ashwin; Zhu, Jenny; Liao, Hsien-Shun; Carvajal, Nicole; Niu, Gang; Eden, Henry; Chen, Xiaoyuan; Jin, Albert J.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
[Fu, Xiao] Beijing Inst Technol, Beijing 100081, Peoples R China.
[Bhirde, Ashwin] US FDA, Silver Spring, MD USA.
NR 1
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 854-Pos
BP 171A
EP 171A
PG 1
WC Biophysics
SC Biophysics
GA DK7GS
UT WOS:000375093800342
ER
PT J
AU Hategan, AP
Karnaukhova, E
Dimitriadis, EK
Bianchet, MA
Nath, A
AF Hategan, Alina Popescu
Karnaukhova, Elena
Dimitriadis, Emilios K.
Bianchet, Mario A.
Nath, Avindra
TI Molecular Study of HIV-Tat Aggregation
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Hategan, Alina Popescu; Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Karnaukhova, Elena] US FDA, CBER, Silver Spring, MD USA.
[Dimitriadis, Emilios K.] NIBIB, Scanning Probe Microscopy Unit, NIH, Bethesda, MD USA.
[Bianchet, Mario A.] Johns Hopkins Sch Med, Dept Neurol & Struct Enzymol, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1976-Pos
BP 400A
EP 400A
PG 1
WC Biophysics
SC Biophysics
GA DK7YE
UT WOS:000375142200444
ER
PT J
AU Lee, JM
Hwang, D
Park, J
Kim, KJ
Ahn, C
Koo, BK
AF Lee, Joo Myung
Hwang, Doyeon
Park, Jonghanne
Kim, Kyung-Jin
Ahn, Chul
Koo, Bon-Kwon
TI Response to Letter Regarding Article, "Percutaneous Coronary
Intervention at Centers With and Without On-Site Surgical Backup: An
Updated Meta-Analysis of 23 Studies"
SO CIRCULATION
LA English
DT Letter
C1 [Lee, Joo Myung; Hwang, Doyeon; Park, Jonghanne; Kim, Kyung-Jin; Koo, Bon-Kwon] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea.
[Lee, Joo Myung; Hwang, Doyeon; Park, Jonghanne; Kim, Kyung-Jin; Koo, Bon-Kwon] Seoul Natl Univ Hosp, Cardiovasc Ctr, Seoul 110744, South Korea.
[Ahn, Chul] Food & Drug Adm, Ctr Devices & Radiol Hlth, Div Biostat, Silver Spring, MD USA.
[Koo, Bon-Kwon] Seoul Natl Univ, Inst Aging, Seoul, South Korea.
RP Lee, JM (reprint author), Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD FEB 16
PY 2016
VL 133
IS 7
BP E407
EP E407
DI 10.1161/CIRCULATIONAHA.115.020201
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DF0DW
UT WOS:000371010200008
PM 26884632
ER
PT J
AU Beaver, JA
AF Beaver, J. A.
TI Development of molecular and genomic biomarkers: A regulatory path
forward
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 [Beaver, J. A.] US FDA, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA ES5-3
DI 10.1158/1538-7445.SABCS15-ES5-3
PG 1
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622400068
ER
PT J
AU Hoffmann, M
Luo, Y
Monday, SR
Gonzalez-Escalona, N
Ottesen, AR
Muruvanda, T
Wang, C
Kastanis, G
Keys, C
Janies, D
Senturk, IF
Catalyurek, UV
Wang, H
Hammack, TS
Wolfgang, WJ
Schoonmaker-Bopp, D
Chu, A
Myers, R
Haendiges, J
Evans, PS
Meng, JH
Strain, EA
Allard, MW
Brown, EW
AF Hoffmann, Maria
Luo, Yan
Monday, Steven R.
Gonzalez-Escalona, Narjol
Ottesen, Andrea R.
Muruvanda, Tim
Wang, Charles
Kastanis, George
Keys, Christine
Janies, Daniel
Senturk, Izzet F.
Catalyurek, Umit V.
Wang, Hua
Hammack, Thomas S.
Wolfgang, William J.
Schoonmaker-Bopp, Dianna
Chu, Alvina
Myers, Robert
Haendiges, Julie
Evans, Peter S.
Meng, Jianghong
Strain, Errol A.
Allard, Marc W.
Brown, Eric W.
TI Tracing Origins of the Salmonella Bareilly Strain Causing a Food-borne
Outbreak in the United States
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE salmonellosis; geographic information systems; next generation
sequencing; single nucleotide polymorphism; traceback
ID INFECTION; EVOLUTION
AB Background. Using a novel combination of whole-genome sequencing (WGS) analysis and geographic metadata, we traced the origins of Salmonella Bareilly isolates collected in 2012 during a widespread food-borne outbreak in the United States associated with scraped tuna imported from India.
Methods. Using next-generation sequencing, we sequenced the complete genome of 100 Salmonella Bareilly isolates obtained from patients who consumed contaminated product, from natural sources, and from unrelated historically and geographically disparate foods. Pathogen genomes were linked to geography by projecting the phylogeny on a virtual globe and produced a transmission network.
Results. Phylogenetic analysis of WGS data revealed a common origin for outbreak strains, indicating that patients in Maryland and New York were infected from sources originating at a facility in India.
Conclusions. These data represent the first report fully integrating WGS analysis with geographic mapping and a novel use of transmission networks. Results showed that WGS vastly improves our ability to delimit the scope and source of bacterial food-borne contamination events. Furthermore, these findings reinforce the extraordinary utility that WGS brings to global outbreak investigation as a greatly enhanced approach to protecting the human food supply chain as well as public health in general.
C1 [Hoffmann, Maria; Monday, Steven R.; Gonzalez-Escalona, Narjol; Ottesen, Andrea R.; Muruvanda, Tim; Wang, Charles; Kastanis, George; Keys, Christine; Wang, Hua; Hammack, Thomas S.; Evans, Peter S.; Allard, Marc W.; Brown, Eric W.] US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Nutr, College Pk, MD USA.
[Luo, Yan; Strain, Errol A.] US FDA, Div Publ Hlth & Biostat, Off Food Def Commun & Emergency Response, Ctr Food Safety & Nutr, College Pk, MD USA.
[Hoffmann, Maria; Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA.
[Hoffmann, Maria; Meng, Jianghong] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA.
[Chu, Alvina; Myers, Robert; Haendiges, Julie] Maryland Dept Hlth & Mental Hyg, Baltimore, MD USA.
[Janies, Daniel] Univ N Carolina, Dept Bioinformat & Genom, Charlotte, NC 28223 USA.
[Senturk, Izzet F.; Catalyurek, Umit V.] Ohio State Univ, Dept Biomed Informat, Columbus, OH 43210 USA.
[Wolfgang, William J.; Schoonmaker-Bopp, Dianna] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12237 USA.
RP Hoffmann, M (reprint author), 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM maria.hoffman@fda.hhs.gov
OI Gonzalez-Escalona, Narjol/0000-0003-4568-0022
FU Joint Institute for Food Safety and Applied Nutrition, University of
Maryland, College Park; Centers for Disease Control and Prevention,
National Center for Infectious Disease, Epidemiology and Laboratory
Capacity for Infectious Diseases [U50/CCU223671]; Defense Threat
Reduction Agency [HDTRA1-14-C-0007]
FX This work was supported by an appointment of MH by the Joint Institute
for Food Safety and Applied Nutrition, University of Maryland, College
Park (appointment to M. H.) and the Centers for Disease Control and
Prevention, National Center for Infectious Disease, Epidemiology and
Laboratory Capacity for Infectious Diseases Cooperative Agreement (grant
U50/CCU223671 to W. J. W. and D. S. B.). The efforts for the geographic
mapping and the novel concept of transmission network were funded by the
Defense Threat Reduction Agency (contract HDTRA1-14-C-0007).
NR 29
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U1 5
U2 10
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD FEB 15
PY 2016
VL 213
IS 4
BP 502
EP 508
DI 10.1093/infdis/jiv297
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DG9XS
UT WOS:000372437700002
PM 25995194
ER
PT J
AU Harrington, PR
Fleischer, R
Connelly, SM
Lewis, LL
Murray, J
AF Harrington, Patrick R.
Fleischer, Russell
Connelly, Sarah M.
Lewis, Linda L.
Murray, Jeffrey
TI Marked Decrease in Lymphocyte Count in HIV/Hepatitis C Virus
(HCV)-Coinfected Patients With Advanced Liver Disease During Anti-HCV
Treatment With Direct-Acting Antiviral Regimens Including Ribavirin
Reply
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Letter
ID HEPATITIS-C
C1 [Harrington, Patrick R.; Fleischer, Russell; Connelly, Sarah M.; Lewis, Linda L.; Murray, Jeffrey] US FDA, Div Antiviral Prod, Off Antimicrobial Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Harrington, PR (reprint author), US FDA, CDER, OAP, DAVP, 10903 New Hampshire Ave,Bldg 22,Rm 6336, Silver Spring, MD 20993 USA.
EM patrick.harrington@fda.hhs.gov
NR 5
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD FEB 15
PY 2016
VL 62
IS 4
BP 528
EP 529
DI 10.1093/cid/civ905
PG 2
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DD9VX
UT WOS:000370274900029
PM 26508511
ER
PT J
AU Krais, AM
Speksnijder, EN
Melis, JPM
Singh, R
Caldwell, A
da Costa, GG
Luijten, M
Phillips, DH
Arlt, VM
AF Krais, Annette M.
Speksnijder, Ewoud N.
Melis, Joost P. M.
Singh, Rajinder
Caldwell, Anna
da Costa, Goncalo Gamboa
Luijten, Mirjam
Phillips, David H.
Arlt, Volker M.
TI Metabolic activation of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine
and DNA adduct formation depends on p53: Studies in Trp53(+/+),
Trp53(+/-) and Trp53(-/-) mice
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE tumor suppressor p53; heterocyclic aromatic hydrocarbon; PhIP;
carcinogen metabolism; DNA adduct formation; cytochrome P450;
sulfotransferases; mouse model; mass spectrometry
ID SULFOTRANSFERASES 1A1; TISSUE DISTRIBUTION; NULL MICE; EXPRESSION;
MOUSE; CARCINOGENS; DEFICIENCY; KNOCKOUT; ENZYMES; TP53
AB The expression of the tumor suppressor p53 can influence the bioactivation of, and DNA damage induced by, the environmental carcinogen benzo[a] pyrene, indicating a role for p53 in its cytochrome P450 (CYP)-mediated biotransformation. The carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which is formed during the cooking of food, is also metabolically activated by CYP enzymes, particularly CYP1A2. We investigated the potential role of p53 in PhIP metabolism in vivo by treating Trp53(+/+), Trp53(+/-) and Trp53(-/-) mice with a single oral dose of 50 mg/kg body weight PhIP. N-(Deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP-C8-dG) levels in DNA, measured by liquid chromatography-tandem mass spectrometry, were significantly lower in liver, colon, forestomach and glandular stomach of Trp53(-/-) mice compared to Trp53(+/+) mice. Lower PhIP-DNA adduct levels in the livers of Trp53(-/-) mice correlated with lower Cyp1a2 enzyme activity (measured by methoxyresorufin-O-demethylase activity) in these animals. Interestingly, PhIP-DNA adduct levels were significantly higher in kidney and bladder of Trp53(-/-) mice compared to Trp53(+/+) mice, which was accompanied by higher sulfotransferase (Sult) 1a1 protein levels and increased Sult1a1 enzyme activity (measured by 2-naphthylsulfate formation from 2-naphthol) in kidneys of these animals. Our study demonstrates a role for p53 in the metabolism of PhIP in vivo, extending previous results on a novel role for p53 in xenobiotic metabolism. Our results also indicate that the impact of p53 on PhIP biotransformation is tissue-dependent and that in addition to Cyp1a enzymes, Sult1a1 can contribute to PhIP-DNA adduct formation.
C1 [Krais, Annette M.; Phillips, David H.; Arlt, Volker M.] Kings Coll London, MRC PHE Ctr Environm & Hlth, Analyt & Environm Sci Div, 150 Stamford St, London SE1 9NH, England.
[Speksnijder, Ewoud N.; Melis, Joost P. M.; Luijten, Mirjam] Natl Inst Publ Hlth & Environm RIVM, Ctr Hlth Protect, NL-3721 MA Bilthoven, Netherlands.
[Speksnijder, Ewoud N.; Melis, Joost P. M.; Luijten, Mirjam] Leiden Univ, Med Ctr, Dept Human Genet, NL-2300 RC Leiden, Netherlands.
[Singh, Rajinder] Univ Leicester, Dept Canc Studies & Mol Med, Leicester LE2 7LX, Leics, England.
[Caldwell, Anna] Kings Coll London, Mass Spectrometry Facil, London SE1 9NH, England.
[da Costa, Goncalo Gamboa] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
RP Arlt, VM (reprint author), Kings Coll London, MRC PHE Ctr Environm & Hlth, Analyt & Environm Sci Div, 150 Stamford St, London SE1 9NH, England.
EM volker.arlt@kcl.ac.uk
FU Cancer Research UK [C313/A14329]; Wellcome Trust [101126/Z/13/Z,
101126/B/13/Z]; German Research Foundation (DFG)
FX Grant sponsor: Cancer Research UK; Grant number: C313/A14329; Grant
sponsor: Wellcome Trust; Grant numbers: 101126/Z/13/Z and 101126/B/13/Z;
Grant sponsor: German Research Foundation (DFG; A.K.)
NR 24
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U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD FEB 15
PY 2016
VL 138
IS 4
BP 976
EP 982
DI 10.1002/ijc.29836
PG 7
WC Oncology
SC Oncology
GA DC4BH
UT WOS:000369164200019
PM 26335255
ER
PT J
AU Alvarado-Facundo, E
Vassell, R
Schmeisser, F
Weir, JP
Weiss, CD
Wang, W
AF Alvarado-Facundo, Esmeralda
Vassell, Russell
Schmeisser, Falko
Weir, Jerry P.
Weiss, Carol D.
Wang, Wei
TI Glycosylation of Residue 141 of Subtype H7 Influenza A Hemagglutinin
(HA) Affects HA-Pseudovirus Infectivity and Sensitivity to Site A
Neutralizing Antibodies
SO PLOS ONE
LA English
DT Article
ID RANDOMIZED CLINICAL-TRIAL; RECEPTOR-BINDING; LENTIVIRAL VECTOR;
IMMUNE-RESPONSE; GENE DELIVERY; CELL-CULTURE; IN-VIVO; VIRUS; VACCINE;
PSEUDOTYPES
AB Human infections with H7 subtype influenza virus have been reported, including an H7N7 outbreak in Netherlands in 2003 and H7N9 infections in China in 2013. Previously, we reported murine monoclonal antibodies (mAbs) that recognize the antigenic site A of H7 hemagglutinin (HA). To better understand protective immunity of H7 vaccines and vaccine candidate selection, we used these mAbs to assess the antigenic relatedness among two H7 HA isolated from past human infections and determine residues that affect susceptibility to neutralization. We found that these mAbs neutralize pseudoviruses bearing HA of A/Shanghai/02/2013(H7N9), but not A/Netherlands/219/2003(H7N7). Glycosylation of the asparagine residue at position 141 (N141) (N133, H3 HA numbering) in the HA of A/Netherlands/219/2003 HA is responsible for this resistance, and it affects the infectivity of HA-pseudoviruses. The presence of threonine at position 143 (T135, H3 HA numbering) in the HA of A/Netherlands/219/2003, rather than an alanine found in the HA of A/Shanghai/02/2013(H7N9), accounts for these differences. These results demonstrate a key role for glycosylation of residue N141 in affecting H7 influenza HA-mediated entry and sensitivity to neutralizing antibodies, which have implications for candidate vaccine design.
C1 [Alvarado-Facundo, Esmeralda; Vassell, Russell; Weiss, Carol D.; Wang, Wei] US FDA, Immunoregulat Lab, Div Viral Prod, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
[Schmeisser, Falko; Weir, Jerry P.] US FDA, Lab DNA Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
RP Weiss, CD; Wang, W (reprint author), US FDA, Immunoregulat Lab, Div Viral Prod, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM carol.weiss@fda.hhs.gov; wei.wang@fda.hhs.gov
FU US Food and Drug Administration; Biomedical Advanced Research and
Development Authority, Department of Health and Human Services
FX This work was supported by the US Food and Drug Administration and the
Biomedical Advanced Research and Development Authority, Department of
Health and Human Services. The funders had no role in the study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 39
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U1 4
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 10
PY 2016
VL 11
IS 2
AR e0149149
DI 10.1371/journal.pone.0149149
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD6PR
UT WOS:000370046600161
PM 26862918
ER
PT J
AU Asati, A
Kachurina, O
Karol, A
Dhir, V
Nguyen, M
Parkhill, R
Kouiavskaia, D
Chumakov, K
Warren, W
Kachurin, A
AF Asati, Atul
Kachurina, Olga
Karol, Alex
Dhir, Vipra
Nguyen, Michael
Parkhill, Robert
Kouiavskaia, Diana
Chumakov, Konstantin
Warren, William
Kachurin, Anatoly
TI Fluorescence Adherence Inhibition Assay: A Novel Functional Assessment
of Blocking Virus Attachment by Vaccine-Induced Antibodies
SO PLOS ONE
LA English
DT Article
ID YELLOW-FEVER VACCINE; FLOW-CYTOMETRY; IMMUNOFLUORESCENCE ASSAY;
NEUTRALIZATION TEST; INFLUENZA-VIRUS; IGG ANTIBODIES; PROTEIN; ELISA;
17D
AB Neutralizing antibodies induced by vaccination or natural infection play a critically important role in protection against the viral diseases. In general, neutralization of the viral infection occurs via two major pathways: pre- and post-attachment modes, the first being the most important for such infections as influenza and polio, the latter being significant for filoviruses. Neutralizing capacity of antibodies is typically evaluated by virus neutralization assays that assess reduction of viral infectivity to the target cells in the presence of functional antibodies. Plaque reduction neutralization test, microneutralization and immunofluorescent assays are often used as gold standard virus neutralization assays. However, these methods are associated with several important prerequisites such as use of live virus requiring safety precautions, tedious evaluation procedure and long assessment time. Hence, there is a need for a robust, inexpensive high throughput functional assay that can be performed rapidly using inactivated virus, without extensive safety precautions. Herein, we report a novel high throughput Fluorescence Adherence Inhibition assay (fADI) using inactivated virus labeled with fluorescent secondary antibodies virus and Vero cells or erythrocytes as targets. It requires only few hours to assess pre-attachment neutralizing capacity of donor sera. fADI assay was tested successfully on donors immunized with polio, yellow fever and influenza vaccines. To further simplify and improve the throughput of the assay, we have developed a mathematical approach for calculating the 50% titers from a single sample dilution, without the need to analyze multi-point titration curves. Assessment of pre- and post-vaccination human sera from subjects immunized with IPOL (R), YF-VAX (R) and 2013-2014 Fluzone (R) vaccines demonstrated high efficiency of the assay. The results correlated very well with microneutralization assay performed independently by the FDA Center of Biologics Evaluation and Research, with plaque reduction neutralization test performed by Focus Diagnostics, and with hemaglutination inhibition assay performed in-house at Sanofi Pasteur. Taken together, fADI assay appears to be a useful high throughput functional immunoassay for assessment of antibody-related neutralization of the viral infections for which pre-attachment neutralization pathway is predominant, such as polio, influenza, yellow fever and dengue.
C1 [Asati, Atul; Kachurina, Olga; Karol, Alex; Dhir, Vipra; Nguyen, Michael; Parkhill, Robert; Warren, William; Kachurin, Anatoly] Sanofi Pasteur VaxDesign Campus, 2501 Discovery Dr Suite 3000, Orlando, FL 32826 USA.
[Kouiavskaia, Diana; Chumakov, Konstantin] US FDA, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
RP Kachurin, A (reprint author), Sanofi Pasteur VaxDesign Campus, 2501 Discovery Dr Suite 3000, Orlando, FL 32826 USA.
EM anatoly.kachurin@sanofipasteur.com
FU Defense Threat Reduction Agency (DTRA) [HDTRA1-13-C-00011]; Biomedical
Advanced Research and Development Authority (BARDA), Department of
Health and Human Services [HHSO100201000035C]; Sanofi Pasteur; CBER FDA
FX This project has been funded in whole or in part with Federal funds from
Defense Threat Reduction Agency (DTRA) and Biomedical Advanced Research
and Development Authority (BARDA), Department of Health and Human
Services, under Contract No. HDTRA1-13-C-00011 and HHSO100201000035C,
respectively. The funders had no role in study design, data collection
and analysis, or preparation of the manuscript. The authors Atul Asati,
Olga Kachurina, Alex Karol, Vipra Dhir, Michael Nguyen, Robert Parkhill,
William Warren and Anatoly Kachurin are employed by Sanofi Pasteur. The
authors Diana Kouiavskaia and Konstantin Chumakov are employed by Center
for Biologics Evaluation and Research within FDA (CBER FDA). Both Sanofi
Pasteur and CBER FDA provided support in the form of salaries for
authors AA, OK, A. Kachurin, VD, MN, RP, WW, A. Karol, DK, and KC
respectively, but did not have any additional role in the study design,
data collection and analysis or preparation of the manuscript. The
specific roles of the authors are articulated in the 'author
contributions' section.
NR 29
TC 0
Z9 0
U1 2
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 10
PY 2016
VL 11
IS 2
AR e0144261
DI 10.1371/journal.pone.0144261
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD6PR
UT WOS:000370046600003
PM 26863313
ER
PT J
AU Hu, J
Juan, W
Sahyoun, NR
AF Hu, Jing
Juan, WenYen
Sahyoun, Nadine R.
TI Intake and Biomarkers of Folate and Risk of Cancer Morbidity in Older
Adults, NHANES 1999-2002 with Medicare Linkage
SO PLOS ONE
LA English
DT Article
ID PROSPECTIVE-PAYMENT SYSTEM; RANDOMIZED CLINICAL-TRIAL; FOLIC-ACID
INTAKE; MULTIVITAMIN USE; UNITED-STATES; COLON-CANCER; CLAIMS DATA;
FORTIFICATION; ACCURACY; WOMEN
AB Background
After the 1998 mandatory folic acid fortification of enriched cereal-grain products in the U.S., safety concerns were raised that excess consumption of folic acid and high blood folate biomarkers detected in adults may increase the risk of certain types of cancer.
Methods
Baseline data from about 1400 participants in the National Health and Nutrition Examination Survey (NHANES) 1999-2002, aged >= 57 years were linked to Medicare and mortality files through December 31, 2007. Using cox proportional hazards regression models, we assessed associations between dietary folate equivalents, folate biomarkers, the presence of unmetabolized folic acid and, overall cancer incidence.
Results
With 8,114 person-years of follow-up (median follow-up, 6.3 years), about 125 cancer cases were identified. After adjusting for confounders, the hazard ratios of the highest quartile versus the second quartile of RBC folate and dietary folate equivalents were 0.54 (95% CI: 0.31-0.93) and 0.54 (95% CI: 0.30-0.95), respectively. Additionally, serum and RBC folate as continuous variables were inversely and significantly associated with cancer incidence (p<0.01). No significant associations were observed between the presence of unmetabolized folic acid, intake of naturally-occurring food folate or folic acid separately, and cancer incidence.
Conclusions
High total folate intake and biomarkers in older adults appear to be protective against cancer in post-folic acid fortification years. This study does not show a negative impact of current level of folic acid fortification on cancer risk. As this is one of the few studies to examine the association between unmetabolized folic acid and cancer outcome, a study including a larger nationwide representative sample of the U.S. population is needed.
C1 [Hu, Jing; Sahyoun, Nadine R.] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA.
[Juan, WenYen] US FDA, Off Nutr Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
RP Sahyoun, NR (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA.
EM nsahyoun@umd.edu
FU Maryland Agricultural Experiment Station (MAES) [MD-HNFS-7307]
FX This work was fully supported by a grant from the Maryland Agricultural
Experiment Station (MAES), MD-HNFS-7307. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript. There was no additional external funding
received for this study.
NR 34
TC 1
Z9 1
U1 4
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 10
PY 2016
VL 11
IS 2
AR e0148697
DI 10.1371/journal.pone.0148697
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD6PR
UT WOS:000370046600098
PM 26862893
ER
PT J
AU Garber, EAE
Parker, CH
Handy, SM
Cho, CY
Panda, R
Samadpour, M
Reynaud, DH
Ziobro, GC
AF Garber, Eric A. E.
Parker, Christine H.
Handy, Sara M.
Cho, Chung Y.
Panda, Rakhi
Samadpour, Mansour
Reynaud, Danica H.
Ziobro, George C.
TI Presence of Undeclared Food Allergens in Cumin: The Need for Multiplex
Methods
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE cumin; peanut; food allergen detection
ID PEANUT ALLERGENS; GLUTEN; ASSAY; KITS
AB Beginning in the autumn of 2014, millions of dollars of food and over 675 products were recalled in the United States due to the presence of undeclared peanut, attributed to cumin used in the manufacture of the products. Initial analyses also indicated the presence of almond. Subsequent research showed that the presence of peanut and almond did not fully explain the analytical results for the cumin samples. Using a combination of mass spectrometry, DNA-based methods (i.e., PCR and Sanger DNA Sequencing), microscopy, and antibody-based technologies (i.e., ELISA, Western blot analysis, and a novel xMAP multiplex assay) the presence of peanut was confirmed. Screening for secondary sources of adulteration (e.g., tree nuts, mahieb, peach, and cherry) supported the assessment that the cumin contained multiple contaminants. These results demonstrate the limitations of single analyte-specific assays and the need for orthogonal multiplex methods to detect food allergens irrespective of varietal or other differences.
C1 [Garber, Eric A. E.; Parker, Christine H.; Handy, Sara M.; Cho, Chung Y.; Panda, Rakhi] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Samadpour, Mansour] IEH Labs & Consulting Grp Inc, Lake Forest Pk, WA 98155 USA.
[Reynaud, Danica H.] AuthenTechnologies LLC, Richmond, CA 94806 USA.
[Ziobro, George C.] US FDA, Off Food Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
RP Garber, EAE (reprint author), US FDA, CFSAN, HFS 716 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM Eric.Garber@fda.hhs.gov
RI Handy, Sara/C-6195-2008
NR 26
TC 2
Z9 2
U1 0
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0021-8561
EI 1520-5118
J9 J AGR FOOD CHEM
JI J. Agric. Food Chem.
PD FEB 10
PY 2016
VL 64
IS 5
BP 1202
EP 1211
DI 10.1021/acs.jafc.5b05497
PG 10
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA DD8ZO
UT WOS:000370215600020
PM 26769163
ER
PT J
AU Shen, J
Lee, K
Choi, S
Qu, W
Wang, Y
Burgess, DJ
AF Shen, Jie
Lee, Kyulim
Choi, Stephanie
Qu, Wen
Wang, Yan
Burgess, Diane J.
TI A reproducible accelerated in vitro release testing method for PLGA
microspheres
SO INTERNATIONAL JOURNAL OF PHARMACEUTICS
LA English
DT Article
DE PLGA microspheres; Porous; Compositionally equivalent; Accelerated in
vitro release; Risperidone; USP apparatus 4
ID POLY(LACTIC-CO-GLYCOLIC ACID) MICROSPHERES; DRUG-RELEASE; BIODEGRADABLE
MICROSPHERES; POLYMERIC MICROSPHERES; VIVO CORRELATION; QUALITY-CONTROL;
MICROPARTICLES; DEGRADATION; DELIVERY; PROTEIN
AB The objective of the present study was to develop a discriminatory and reproducible accelerated in vitro release method for long-acting PLGA microspheres with inner structure/porosity differences. Risperidone was chosen as a model drug. Qualitatively and quantitatively equivalent PLGA microspheres with different inner structure/porosity were obtained using different manufacturing processes. Physicochemical properties as well as degradation profiles of the prepared microspheres were investigated. Furthermore, in vitro release testing of the prepared risperidone microspheres was performed using the most common in vitro release methods (i.e., sample-and-separate and flow through) for this type of product. The obtained compositionally equivalent risperidone microspheres had similar drug loading but different inner structure/porosity. When microsphere particle size appeared similar, porous risperidone microspheres showed faster microsphere degradation and drug release compared with less porous microspheres. Both in vitro release methods investigated were able to differentiate risperidone microsphere formulations with differences in porosity under real-time (37 degrees C) and accelerated (45 degrees C) testing conditions. Notably, only the accelerated USP apparatus 4 method showed good reproducibility for highly porous risperidone microspheres. These results indicated that the accelerated USP apparatus 4 method is an appropriate fast quality control tool for long-acting PLGA microspheres (even with porous structures). (C) 2015 Elsevier B.V. All rights reserved.
C1 [Shen, Jie; Lee, Kyulim; Burgess, Diane J.] Univ Connecticut, Sch Pharm, Storrs, CT 06269 USA.
[Choi, Stephanie; Qu, Wen; Wang, Yan] US FDA, Off Res & Stand, Off Gener Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Burgess, DJ (reprint author), Univ Connecticut, Sch Pharm, Dept Pharmaceut Sci, 69 North Eagleville Rd U3092, Storrs, CT 06269 USA.
EM d.burgess@uconn.edu
FU Office of Research and Standards, Office of Generic Drugs, CDER at the
FDA [1U01FD004931-01]; Sotax Corporation
FX This work was financially supported by the Office of Research and
Standards, Office of Generic Drugs, CDER at the FDA (1U01FD004931-01).
Support from Sotax Corporation is highly appreciated.
NR 31
TC 4
Z9 4
U1 9
U2 35
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5173
EI 1873-3476
J9 INT J PHARMACEUT
JI Int. J. Pharm.
PD FEB 10
PY 2016
VL 498
IS 1-2
BP 274
EP 282
DI 10.1016/j.ijpharm.2015.12.031
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB1SW
UT WOS:000368290200028
PM 26705156
ER
PT J
AU Hung, HMJ
Wang, SJ
Lawrence, J
AF Hung, H. M. J.
Wang, Sue-Jane
Lawrence, John
TI Comments on "Twenty-five years of confirmatory adaptive designs:
opportunities and pitfalls'
SO STATISTICS IN MEDICINE
LA English
DT Editorial Material
C1 [Hung, H. M. J.; Lawrence, John] FDA, OB OTS CDER, Div Biometr 1, Silver Spring, MD 20993 USA.
[Wang, Sue-Jane] FDA, OTS CDER, Off Biostat, Silver Spring, MD 20993 USA.
RP Hung, HMJ (reprint author), FDA, OB OTS CDER, Div Biometr 1, Silver Spring, MD 20993 USA.
EM hmjames.hung@gmail.com
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD FEB 10
PY 2016
VL 35
IS 3
BP 348
EP 349
DI 10.1002/sim.6806
PG 2
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA DA7GP
UT WOS:000367972900002
PM 26757952
ER
PT J
AU Federhen, S
Rossello-Mora, R
Klenk, HP
Tindall, BJ
Konstantinidis, KT
Whitman, WB
Brown, D
Labeda, D
Ussery, D
Garrity, GM
Colwell, RR
Hasan, N
Graf, J
Parte, A
Yarza, P
Goldberg, B
Sichtig, H
Karsch-Mizrachi, I
Clark, K
McVeigh, R
Pruitt, KD
Tatusova, T
Falk, R
Turner, S
Madden, T
Kitts, P
Kimchi, A
Klimke, W
Agarwala, R
DiCuccio, M
Ostell, J
AF Federhen, Scott
Rossello-Mora, Ramon
Klenk, Hans-Peter
Tindall, Brian J.
Konstantinidis, Konstantinos T.
Whitman, William B.
Brown, Daniel
Labeda, David
Ussery, David
Garrity, George M.
Colwell, Rita R.
Hasan, Nur
Graf, Joerg
Parte, Aidan
Yarza, Pablo
Goldberg, Brittany
Sichtig, Heike
Karsch-Mizrachi, Ilene
Clark, Karen
McVeigh, Richard
Pruitt, Kim D.
Tatusova, Tatiana
Falk, Robert
Turner, Sean
Madden, Thomas
Kitts, Paul
Kimchi, Avi
Klimke, William
Agarwala, Richa
DiCuccio, Michael
Ostell, James
TI Meeting report: GenBank microbial genomic taxonomy workshop (12-13 May,
2015)
SO STANDARDS IN GENOMIC SCIENCES
LA English
DT Article
DE GenBank; Genomic taxonomy; Misidentified sequence entries
ID SPECIES DEFINITION; PROKARYOTES; BACTERIA; ARCHAEA
AB Many genomes are incorrectly identified at GenBank. We developed a plan to find and correct misidentified genomes using genomic comparison statistics together with a scaffold of reliably identified genomes from type. A workshop was organized with broad representation from the bacterial taxonomic community to review the proposal, the GenBank Microbial Genomic Taxonomy Workshop, Bethesda MD, May 12-13, 2015.
C1 [Federhen, Scott; Karsch-Mizrachi, Ilene; Clark, Karen; McVeigh, Richard; Pruitt, Kim D.; Tatusova, Tatiana; Falk, Robert; Turner, Sean; Madden, Thomas; Kitts, Paul; Kimchi, Avi; Klimke, William; Agarwala, Richa; DiCuccio, Michael; Ostell, James] NCBI, Bethesda, MD USA.
[Rossello-Mora, Ramon] IMEDEA CSIC UIB, Esporles, Spain.
[Klenk, Hans-Peter] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Tindall, Brian J.] Deutsch Sammlung Mikroorganism Zellkultur GmbH, Braunschweig, Germany.
[Konstantinidis, Konstantinos T.] Georgia Inst Technol, Atlanta, GA 30332 USA.
[Whitman, William B.] Univ Georgia, Athens, GA 30602 USA.
[Brown, Daniel] Univ Florida, Gainesville, FL USA.
[Labeda, David] USDA, Washington, DC 20250 USA.
[Ussery, David] Oak Ridge Natl Lab, Oak Ridge, TN USA.
[Garrity, George M.] Michigan State Univ, E Lansing, MI 48824 USA.
[Colwell, Rita R.] Univ Maryland, College Pk, MD 20742 USA.
[Hasan, Nur] CosmosID, Rockville, MD USA.
[Graf, Joerg] Univ Connecticut, Storrs, CT USA.
[Parte, Aidan] LPSN, New York, NY USA.
[Yarza, Pablo] Ribocon, Bremen, Germany.
[Goldberg, Brittany; Sichtig, Heike] US FDA, Silver Spring, MD USA.
RP Federhen, S (reprint author), NCBI, Bethesda, MD USA.
EM federhen@ncbi.nlm.nih.gov
OI Parte, Aidan/0000-0002-6304-4217; Ussery, David/0000-0003-3632-5512;
Graf, Joerg/0000-0001-5320-2712
NR 17
TC 7
Z9 7
U1 2
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1944-3277
J9 STAND GENOMIC SCI
JI Stand. Genomic Sci.
PD FEB 9
PY 2016
VL 11
AR 15
DI 10.1186/s40793-016-0134-1
PG 8
WC Genetics & Heredity; Microbiology
SC Genetics & Heredity; Microbiology
GA DO7FR
UT WOS:000377948300002
ER
PT J
AU Lin, YC
Winokur, P
Blake, A
Wu, TX
Manischewitz, J
King, LR
Romm, E
Golding, H
Bielekova, B
AF Lin, Yen Chih
Winokur, Paige
Blake, Andrew
Wu, Tianxia
Manischewitz, Jody
King, Lisa R.
Romm, Elena
Golding, Hana
Bielekova, Bibiana
TI Patients with MS under daclizumab therapy mount normal immune responses
to influenza vaccination
SO NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
LA English
DT Article
ID HIGH-YIELD PROCESS; MULTIPLE-SCLEROSIS; DOUBLE-BLIND; ALPHA-CHAIN;
T-CELLS; INTERLEUKIN-2; ANTIBODY; RECEPTOR; TRIAL; LYMPHOCYTES
AB Objective: The purpose of this study was to assess the potential immunosuppressive role of daclizumab, a humanized monoclonal antibody against the a chain of the interleukin 2 receptor, in vivo, by comparing immune responses to the 2013 seasonal influenza vaccination between patients with multiple sclerosis (MS) on long-term daclizumab therapy and controls.
Methods: Previously defined subpopulations of adaptive immune cells known to correlate with the immune response to the influenza vaccination were evaluated by 12-color flow cytometry in 23 daclizumab-treated patients with MS and 14 MS or healthy controls before (D0) and 1 day (D1) and 7 days (D7) after administration of the 2013 Afluria vaccine. Neutralizing antibody titers and CD4(+), CD8(+) T cell, B cell, and natural killer cell proliferation to 3 strains of virus contained in the Afluria vaccine were assessed at D0, D7, and 180 days postvaccination.
Results: Daclizumab-treated patients and controls demonstrated comparable, statistically significant expansions of previously defined subpopulations of activated CD8(+) T cells and B cells that characterize the development of effective immune responses to the influenza vaccine, while proliferation of T cells to influenza and control antigens was diminished in the daclizumab cohort. All participants fulfilled FDA criteria for seroconversion or seroprotection in antibody assays.
Conclusion: Despite the mild immunosuppressive effects of daclizumab in vivo demonstrated by an increased incidence of infectious complications in clinical trials, patients with MS under daclizumab therapy mount normal antibody responses to influenza vaccinations. Neurol Neuroimmunol Neuroinflamm 2016;3:e196; doi: 10.1212/NXI.0000000000000196
C1 [Lin, Yen Chih; Winokur, Paige; Blake, Andrew; Romm, Elena; Bielekova, Bibiana] NINDS, Neuroimmunol Dis Unit, Neuroimmunol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Wu, Tianxia] NINDS, Clin Neurosci Program, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Manischewitz, Jody; King, Lisa R.; Golding, Hana] US FDA, CBER, Rockville, MD 20857 USA.
[Bielekova, Bibiana] NIH, Ctr Human Immunol, Bldg 10, Bethesda, MD 20892 USA.
RP Bielekova, B (reprint author), NINDS, Neuroimmunol Dis Unit, Neuroimmunol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM bibi.bielekova@nih.gov
NR 26
TC 3
Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 2332-7812
J9 NEUROL-NEUROIMMUNOL
JI Neurol.-Neuroimmunol. Neuroinflammation
PD FEB
PY 2016
VL 3
IS 1
AR e196
DI 10.1212/NXI.0000000000000196
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA DX7MT
UT WOS:000384572500014
PM 26848487
ER
PT J
AU Bai, JPF
Burckart, GJ
Mulberg, AE
AF Bai, Jane P. F.
Burckart, Gilbert J.
Mulberg, Andrew E.
TI Literature Review of Gastrointestinal Physiology in the Elderly, in
Pediatric Patients, and in Patients with Gastrointestinal Diseases
SO JOURNAL OF PHARMACEUTICAL SCIENCES
LA English
DT Review
DE paracellular transport; passive transport disease effects; pediatric;
gastrointestinal transit; permeabiltiy; elderly; CYP enzymes;
transporters; metabolism; solubility
ID IRRITABLE-BOWEL-SYNDROME; INTESTINAL TRANSIT-TIME; AGE-RELATED-CHANGES;
MESSENGER-RNA EXPRESSION; CROHNS-DISEASE; ULCERATIVE-COLITIS;
P-GLYCOPROTEIN; GASTROESOPHAGEAL-REFLUX; HEALTHY-VOLUNTEERS; DRUG
ABSORPTION
AB Oral bioavailability studies during the development of new medical entities or generic drugs are typically performed in healthy volunteers. Approved drug products are, however, used by patients with diverse disease backgrounds, and by pediatric and elderly patients. To provide the knowledge base for assessing the potential effects of age or co-morbidity on the in vivo performance of an orally absorbed, systemically active drug product, the literature regarding the gastrointestinal (GI) physiological characteristics (pH, permeability, and transit time) in children, in the elderly, and in patients with GI diseases (irritable bowel syndrome, ulcerative colitis, and Crohn's disease) is reviewed herein, with the knowledge gaps highlighted. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
C1 [Bai, Jane P. F.; Burckart, Gilbert J.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Mulberg, Andrew E.] US FDA, Div Gastroenterol & Inborn Error Prod, Off Drug Evaluat 3, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Bai, JPF (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
EM jane.bai@fda.hhs.gov
NR 75
TC 3
Z9 3
U1 4
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3549
EI 1520-6017
J9 J PHARM SCI-US
JI J. Pharm. Sci.
PD FEB
PY 2016
VL 105
IS 2
BP 476
EP 483
DI 10.1002/jps.24696
PG 8
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology &
Pharmacy
SC Pharmacology & Pharmacy; Chemistry
GA DT8TQ
UT WOS:000381768500011
PM 26539698
ER
PT J
AU Yang, YS
Mohammad, A
Berendt, RT
Carlin, A
Khan, MA
Faustino, PJ
AF Yang, Yongsheng
Mohammad, Adil
Berendt, Robert T.
Carlin, Alan
Khan, Mansoor A.
Faustino, Patrick J.
TI Evaluation of the In Vitro Efficacy of Sevelamer Hydrochloride and
Sevelamer Carbonate
SO JOURNAL OF PHARMACEUTICAL SCIENCES
LA English
DT Article
DE sevelamer; inductively coupled plasma; phosphate binding; langmuir
equation; bioequivalence; polymeric drugs; kinetics; absorption; drug
interaction
ID CHRONIC-RENAL-FAILURE; CHRONIC KIDNEY-DISEASE; LANTHANUM CARBONATE;
PHOSPHATE BINDERS; CLINICAL-IMPLICATIONS; CALCIUM-CARBONATE; DIALYSIS;
HYPERPHOSPHATEMIA; SAFETY; MEAL
AB The objective of this project is to develop an in vitro approach that can be used to determine the phosphate binding capacity of sevelamer hydrochloride and carbonate for both drug products and active pharmaceutical ingredients (APIs). A simple and efficient inductively coupled plasma spectrometer method for analysis of phosphate at physiologically relevant pH conditions has been developed and validated. The method addresses each of the analytical validation characteristics such as linearity, accuracy, precision, stability, and selectivity, and meets the acceptance criteria defined in the United States Food and Drug Administration guidance (Food and Drug Administration, Center for Drug Evaluation and Research. 2001. Guidance for industry-Bioanalytical method validation, May). The in vitro phosphate binding efficacies were systematically evaluated and compared for two drug products and two APIs. The phosphate binding profiles appeared similar between the drug products. Under all conditions, the sevelamer-phosphate binding reached equilibrium at 6 h. The 90% confidence interval for the k(2) ratio (sevelamer carbonate vs. sevelamer hydrochloride) was well within 80%-125% under all pH conditions. However, the k(1) ratio varied, indicating that there exists difference in the binding affinity. Our findings will be useful in assisting with "in vivo" biowaiver for the approval of generic sevelamer drug products. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
C1 [Yang, Yongsheng; Mohammad, Adil; Carlin, Alan; Khan, Mansoor A.; Faustino, Patrick J.] US FDA, Div Prod Qual Res, Off Pharmaceut Qual, Life Sci Bldg 64, Silver Spring, MD 20993 USA.
[Berendt, Robert T.] US FDA, Off Lifecycle Drug Prod, Off Pharmaceut Qual, Life Sci Bldg 75, Silver Spring, MD 20993 USA.
RP Yang, YS (reprint author), US FDA, Div Prod Qual Res, Off Pharmaceut Qual, Life Sci Bldg 64, Silver Spring, MD 20993 USA.
EM yongsheng.yang@fda.hhs.gov
NR 32
TC 0
Z9 0
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3549
EI 1520-6017
J9 J PHARM SCI-US
JI J. Pharm. Sci.
PD FEB
PY 2016
VL 105
IS 2
BP 864
EP 875
DI 10.1002/jps.24572
PG 12
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology &
Pharmacy
SC Pharmacology & Pharmacy; Chemistry
GA DT8TQ
UT WOS:000381768500053
PM 26219932
ER
PT J
AU Vaithianathan, S
Haidar, SH
Zhang, XY
Jiang, WL
Avon, C
Dowling, TC
Shao, CX
Kane, M
Hoag, SW
Flasar, MH
Ting, TY
Polli, JE
AF Vaithianathan, Soundarya
Haidar, Sam H.
Zhang, Xinyuan
Jiang, Wenlei
Avon, Christopher
Dowling, Thomas C.
Shao, Changxing
Kane, Maureen
Hoag, Stephen W.
Flasar, Mark H.
Ting, Tricia Y.
Polli, James E.
TI Effect of Common Excipients on the Oral Drug Absorption of
Biopharmaceutics Classification System Class 3 Drugs Cimetidine and
Acyclovir
SO JOURNAL OF PHARMACEUTICAL SCIENCES
LA English
DT Article
DE Biopharmaceutics Classification System (BCS); bioequivalence;
excipients; oral absorption; permeability; cimetidine; acyclovir
ID IN-VIVO BIOAVAILABILITY; LOW-PERMEABILITY DRUGS; DOSAGE FORMS;
LIQUID-CHROMATOGRAPHY; BIOWAIVER MONOGRAPHS; CAPSULE FORMULATIONS; CELL
MONOLAYERS; WORKSHOP REPORT; RELEASE; BIOEQUIVALENCE
AB The objective was to assess the impact of larger than conventional amounts of 14 commonly used excipients on Biopharmaceutics Classification System (BCS) class 3 drug absorption in humans. Cimetidine and acyclovir were used as model class 3 drugs across three separate four-way crossover bioequivalence (BE) studies (n = 24 each) in healthy human volunteers, denoted as study 1A, 1B, and 2. In study 1A and 1B, three capsule formulations of each drug were manufactured, collectively involving 14 common excipients. Capsule formulations that incorporated hydroxypropyl methylcellulose (HPMC) or magnesium stearate exhibited lower absorption. The cimetidine commercial solution contained sorbitol and also resulted in lower absorption. Hence, in study 2, two capsule formulations with lower amounts of HPMC and magnesium stearate, the sorbitol-containing commercial solution, and a sorbitol-free solution were assessed for BE. Overall, 12 common excipients were found in large amounts to not impact BCS class 3 drug absorption in humans, such that these excipients need not be qualitatively the same nor quantitatively very similar to reference, but rather simply be not more than the quantities studied here. Meanwhile, for each HPMC and microcrystalline cellulose, BCS class 3 biowaivers require these two excipients to be qualitatively the same and quantitatively very similar to the reference. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
C1 [Vaithianathan, Soundarya; Avon, Christopher; Shao, Changxing; Kane, Maureen; Hoag, Stephen W.; Polli, James E.] Univ Maryland, Dept Pharmaceut Sci, Baltimore, MD 21201 USA.
[Haidar, Sam H.; Zhang, Xinyuan; Jiang, Wenlei] US FDA, Silver Spring, MD 20993 USA.
[Dowling, Thomas C.] Ferris State Univ, Dept Pharm Practice, Grand Rapids, MI 49503 USA.
[Flasar, Mark H.] Univ Maryland, Dept Gastroenterol & Hepatol, Baltimore, MD 21201 USA.
[Ting, Tricia Y.] Univ Maryland, Dept Neurol, Baltimore, MD 21201 USA.
RP Polli, JE (reprint author), Univ Maryland, Dept Pharmaceut Sci, Baltimore, MD 21201 USA.
EM jpolli@rx.umaryland.edu
RI Dowling, Thomas/D-2147-2013
OI Dowling, Thomas/0000-0003-3214-9283
FU US FDA contracts [HHSF223200910020C, HHSF223200810041C]; University of
Maryland Clinical Translational Science Institute; University of
Maryland General Clinical Research Center; University of Maryland Mass
Spectrometry Center [S0P1841-IQB2014]
FX This work was supported by US FDA contracts HHSF223200910020C and
HHSF223200810041C. This work was supported in part by the University of
Maryland Clinical Translational Science Institute, the University of
Maryland General Clinical Research Center, and the University of
Maryland Mass Spectrometry Center (S0P1841-IQB2014).
NR 44
TC 2
Z9 2
U1 6
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3549
EI 1520-6017
J9 J PHARM SCI-US
JI J. Pharm. Sci.
PD FEB
PY 2016
VL 105
IS 2
BP 996
EP 1005
DI 10.1002/jps.24643
PG 10
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology &
Pharmacy
SC Pharmacology & Pharmacy; Chemistry
GA DT8TQ
UT WOS:000381768500068
PM 26375604
ER
PT J
AU Chin, SJ
Durmowicz, AG
Chowdhury, BA
AF Chin, Stacy J.
Durmowicz, Anthony G.
Chowdhury, Badrul A.
TI Tiotropium Respimat Is Effective for the Treatment of Asthma at a Dose
Lower Than That for Chronic Obstructive Pulmonary Disease
SO ANNALS OF THE AMERICAN THORACIC SOCIETY
LA English
DT Article
AB Anticholinergic drug products are not part of the current treatment paradigm for asthma, despite their widespread availability for chronic obstructive pulmonary disease (COPD) and interest in their use for asthma. Published study results, mostly of short duration and primarily with ipratropium and tiotropium, have revealed inconsistent efficacy results. Consequently, the role of inhaled anticholinergic drugs in the treatment of asthma has been unclear. This commentary discusses and comments on data from five clinical trials in adults that were submitted by Boehringer Ingelheim to the U.S. Food and Drug Administration to support approval of tiotropium delivered by the Respimat device (Spiriva Respimat) for the treatment of asthma. These trials provided substantial evidence that supported the approval of Spiriva Respimat at a recommended dose of 2.5 mu g once daily for asthma. Notably, in trials that evaluated two doses of tiotropium, 2.5 mu g and 5 mu g (the dose approved for COPD), pulmonary function measures for Spiriva Respimat 2.5 mu g once daily were better overall than those obtained for the 5-mu g once-daily dose, thus justifying selection of the lower dose for asthma. Spiriva Respimat represents the first new class of drug approved by the U.S. Food and Drug Administration for the treatment of asthma in more than a decade. The availability of Spiriva Respimat for asthma along with other novel therapies currently under development has the potential to impact asthma treatment guidelines.
C1 [Chin, Stacy J.; Durmowicz, Anthony G.; Chowdhury, Badrul A.] US FDA, Div Pulm Allergy & Rheumatol Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
RP Chin, SJ (reprint author), US FDA, Div Pulm Allergy & Rheumatol Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM stacy.chin@fda.hhs.gov
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1546-3222
EI 2325-6621
J9 ANN AM THORAC SOC
JI Ann. Am. Thoracic Society
PD FEB
PY 2016
VL 13
IS 2
BP 173
EP 179
DI 10.1513/AnnalsATS.201510-712PS
PG 7
WC Respiratory System
SC Respiratory System
GA DQ4HJ
UT WOS:000379164400008
PM 26650145
ER
PT J
AU Tyson, GH
Li, C
Ayers, S
McDermott, PF
Zhao, SH
AF Tyson, Gregory H.
Li, Cong
Ayers, Sherry
McDermott, Patrick F.
Zhao, Shaohua
TI Using whole-genome sequencing to determine appropriate streptomycin
epidemiological cutoffs for Salmonella and Escherichia coli
SO FEMS MICROBIOLOGY LETTERS
LA English
DT Article
DE Salmonella; E. coli; whole-genome sequencing; streptomycin; resistance;
genotyping
ID ANTIMICROBIAL RESISTANCE; NUCLEOTIDE-SEQUENCE; SURVEILLANCE; ANIMALS;
HUMANS; VALUES
AB For Enterobacteriaceae such as Salmonella spp. and Escherichia coli, no unified interpretive resistance criteria exist for streptomycin, an epidemiologically important antibiotic. As part of the National Antimicrobial Resistance Monitoring System, we had previously used a minimum inhibitory concentration of >= 64 mu g mL(-1) as an epidemiological cutoff value (ECV) to define non-wild-type isolates. To identify whether this ECV correlated with genetic determinants of resistance, we performed whole-genome sequencing of 463 Salmonella and E. coli isolates to identify streptomycin resistance genotypes. From this analysis, we found that using a streptomycin resistance breakpoint of >= 64 mu g mL(-1)1 classified over 20% of strains possessing aadA or strA/strB resistance genes as wild-type. Therefore, to improve the concordance between genotypic and phenotypic data, we propose reducing the phenotypic cutoff values to >= 32 mu g mL(-1) for both Salmonella and E. coli, to be used widely as ECVs to categorize non-wild-type isolates.
C1 [Tyson, Gregory H.; Li, Cong; Ayers, Sherry; McDermott, Patrick F.; Zhao, Shaohua] US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA.
RP Tyson, GH (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA.
EM gregory.tyson@fda.hhs.gov
NR 17
TC 3
Z9 3
U1 1
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0378-1097
EI 1574-6968
J9 FEMS MICROBIOL LETT
JI FEMS Microbiol. Lett.
PD FEB
PY 2016
VL 363
IS 4
AR fnw009
DI 10.1093/femsle/fnw009
PG 5
WC Microbiology
SC Microbiology
GA DO7MI
UT WOS:000377966300008
ER
PT J
AU Alrwisan, A
Eworuke, E
AF Alrwisan, Adel
Eworuke, Efe
TI ARE DISCREPANCIES IN WAITING TIME FOR CHEST PAIN AT EMERGENCY
DEPARTMENTS BETWEEN AFRICAN AMERICANS AND WHITES IMPROVING OVER TIME?
SO JOURNAL OF EMERGENCY MEDICINE
LA English
DT Article
DE African American; disparity; emergency department; race; waiting time
ID UNITED-STATES; DISPARITIES; INSURANCE; CARE
AB Background: One of the Healthy People 2010 goals was to eliminate racial disparities in the U.S health system. To date, we have limited knowledge about the impact of Healthy People on racial disparities at emergency departments (EDs). Objective: We sought to investigate whether there has been an improvement in ED waiting time to see a physician for African Americans (AAs) compared to whites with chest pain symptoms that suggest acute coronary syndrome (ACS). Methods: A retrospective analysis of the National Hospital and Ambulatory Care Survey data from 2004 to 2011 was conducted in adults with visits related to ACS. We compared covariate-adjusted odds ratios for race for each study year and 2011. In addition, adjusted average differences in waiting times (i.e., time to see a physician) for AAs and whites for each study year were compared. Results: A total of 15,438 visits related to ACS symptoms were made during the study period. The waiting time for AAs (median, 33 min) was statistically longer compared to whites (median, 21 min). In addition, the adjusted waiting time for AAs was 30% longer compared to whites (95% confidence interval, 24-36%). Pairwise comparison of adjusted odds ratios between the year 2011 and other years was not significantly different (all p values = 0.32), suggesting no change in the difference in waiting times during the study period. Conclusion: Among patients presenting to the ED with symptoms suggesting ACS, AA compared to whites waited longer to receive care. In addition, this difference in waiting time persisted during the study period, even after the implementation of the Healthy People 2010 initiative. Additional research is warranted to investigate the underlying reasons for unequal care offered to AAs at EDs and the implications on disease outcome. (C) 2016 Elsevier Inc.
C1 [Alrwisan, Adel] Univ Florida, Coll Pharm, Dept Pharmaceut Outcomes & Policy, POB 100496, Gainesville, FL 32610 USA.
[Alrwisan, Adel] Saudi Food & Drug Author Vigilance & Crisis Manag, Riyadh, Saudi Arabia.
[Eworuke, Efe] US FDA, Div Epidemiol 2, Off Pharmacovigilance & Epidemiol, Off Surveillance & Epidemiol,Ctr Drug Evaluat & R, Washington, DC 20204 USA.
RP Alrwisan, A (reprint author), Univ Florida, Coll Pharm, Dept Pharmaceut Outcomes & Policy, POB 100496, Gainesville, FL 32610 USA.
NR 21
TC 1
Z9 1
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0736-4679
EI 1090-1280
J9 J EMERG MED
JI J. Emerg. Med.
PD FEB
PY 2016
VL 50
IS 2
BP 349
EP 354
DI 10.1016/j.jemermed.2015.07.033
PG 6
WC Emergency Medicine
SC Emergency Medicine
GA DI2BB
UT WOS:000373299600041
PM 26371975
ER
PT J
AU Breslin, ME
Hamilton, DK
Guo, RS
Ye, P
Jiang, XT
Stewart, P
Chin, S
Kim, EH
Burks, AW
AF Breslin, Moira E.
Hamilton, Deanna K.
Guo, Rishu
Ye, Ping
Jiang, Xiaotong
Stewart, Paul
Chin, Stacy
Kim, Edwin H.
Burks, A. Wesley
TI Basophil Activation and Peanut-Specific IgE Are Not Predictors of
Threshold Dose during a Double-Blind Placebo-Controlled Food Challenge
(DBPCFC)
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Breslin, Moira E.; Hamilton, Deanna K.; Guo, Rishu; Ye, Ping; Jiang, Xiaotong; Stewart, Paul; Kim, Edwin H.; Burks, A. Wesley] Univ N Carolina, Chapel Hill, NC USA.
[Chin, Stacy] US FDA, CDER, Washington, DC 20204 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA 414
BP AB125
EP AB125
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005402104
ER
PT J
AU Khurana, T
Shartouny, JR
David, NA
Slater, JE
AF Khurana, Taruna
Shartouny, Jessica R.
David, Natalie A.
Slater, Jay E.
TI Measurement of Major Allergen Mus m 1 in Commercial Mouse Allergen
Extracts and Mouse Urine
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Khurana, Taruna; Shartouny, Jessica R.; David, Natalie A.; Slater, Jay E.] FDA, CBER, OVRR, DBPAP, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA 595
BP AB182
EP AB182
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005403041
ER
PT J
AU Kwegyir-Afful, EK
Westermann-Clark, E
Zhang, YT
Luccioli, S
AF Kwegyir-Afful, Ernest K.
Westermann-Clark, Emma
Zhang, Yuanting
Luccioli, Stefano
TI Food Diversity, Breastfeeding Frequency, and the Incidence of Food
Allergy and Eczema in the First Year of Life
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Kwegyir-Afful, Ernest K.; Zhang, Yuanting; Luccioli, Stefano] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
[Westermann-Clark, Emma] Univ S Florida, Dept Internal Med, Morsani Coll Med, Tampa, FL 33612 USA.
NR 0
TC 0
Z9 0
U1 3
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA 481
BP AB147
EP AB147
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005402172
ER
PT J
AU Mattison, CP
Khurana, T
Tarver, M
Florane, C
Grimm, CC
Pakala, S
Cottone, C
Riegel, C
Slater, JE
AF Mattison, Christopher P.
Khurana, Taruna
Tarver, Matthew
Florane, Christopher
Grimm, Casey C.
Pakala, Suman
Cottone, Carrie
Riegel, Claudia
Slater, Jay E.
TI Termite Proteins Cross-React with Cockroach Allergens
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Mattison, Christopher P.; Florane, Christopher; Grimm, Casey C.] USDA ARS, SRRC, New Orleans, LA USA.
[Khurana, Taruna; Slater, Jay E.] US FDA, CBER, OVRR, DBPAP, Silver Spring, MD USA.
[Tarver, Matthew] Bayer CropSci, West Sacramento, CA USA.
[Pakala, Suman] Univ Georgia, Athens, GA 30602 USA.
[Cottone, Carrie; Riegel, Claudia] New Orleans Mosquito Termite & Rodent Control Boa, New Orleans, LA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA 872
BP AB266
EP AB266
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005404068
ER
PT J
AU Rabin, RL
Novatt, H
Theisen, TC
Renn, LA
AF Rabin, Ronald L.
Novatt, Hilary
Theisen, Terence C.
Renn, Lynnsey A.
TI Patterns of Interferon Regulatory Factor 1 (IRF1) Expression By
Respiratory Epithelial Cells Reveal Non-Redundancy of Type I Versus Type
III Interferons
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Rabin, Ronald L.] US FDA, CBER, Silver Spring, MD USA.
[Novatt, Hilary] US FDA, Ctr Biol & Evaluat, Silver Spring, MD USA.
[Novatt, Hilary; Theisen, Terence C.; Renn, Lynnsey A.] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA L50
BP AB405
EP AB405
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005405031
ER
PT J
AU Jarow, JP
Ahmed, HU
Choyke, PL
Taneja, SS
Scardino, PT
AF Jarow, Jonathan P.
Ahmed, Hashim U.
Choyke, Peter L.
Taneja, Samir S.
Scardino, Peter T.
TI Partial Gland Ablation for Prostate Cancer: Report of a Food and Drug
Administration, American Urological Association, and Society of Urologic
Oncology Public Workshop
SO UROLOGY
LA English
DT Article
ID FOCAL THERAPY; CONSENSUS PANEL; ULTRASOUND; PATHWAY; BIOPSY
AB OBJECTIVE To summarize the discussion that took place at a public workshop, co-sponsored by the U.S. Food and Drug Administration, the American Urological Association, and Society of Urologic Oncology reviewing the current state of the art for partial gland ablation (PGA) for the management of patients with prostate cancer. The purpose of this workshop was to discuss potential indications, current available evidence, and designs for future trials to provide the evidence needed by patients and providers to decide how and when to use PGA.
METHODS A workshop evaluating PGA for prostate cancer was held in New Orleans, Louisiana, in May 2015. Invited experts representing all stakeholders and attendees discussed the regulatory development of medical products, technology available, potential indications, and designs of trials to evaluate this modality of therapy.
RESULTS The panel presented the current information on the technologies available to perform PGA, the potential indications, and results of prior consensus conferences. Use of magnetic resonance imaging for patient selection, guide therapy, and follow-up was discussed. Designs of trials to assess PGA outcomes were discussed.
CONCLUSION The general consensus was that currently available technologies are capable of selective ablation with reasonable accuracy, but that criteria for patient selection remain debatable, and long-term cancer control remains to be established in properly designed and well-performed prospective clinical trials. Concerns include the potential for excessive, unnecessary use in patients with low-risk cancer and, conversely, that current diagnostic techniques may underestimate the extent and aggressiveness of some cancers, leading to inadequate treatment. Published by Elsevier Inc.
C1 US FDA, CDER Off Med Policy, Silver Spring, MD USA.
UCL, Div Surg & Intervent Sci, London, England.
NCI, Ctr Canc Res, Reston, VA USA.
NYU, Langone Med Ctr, Div Urol Oncol, New York, NY USA.
Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10021 USA.
RP Jarow, JP (reprint author), Off Med Policy, WO51 RM6338,10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM jonathan.jarow@fda.hhs.gov
FU Sonacare Inc.; Trod Medical; Sophiris Biocorp; Biobot; Hitachi-Aloka
FX Hashim U. Ahmed received clinical trial funding from Sonacare Inc., and
also funding for conference travel and honoraria for lectures at courses
organized by the said company. He is currently a paid proctor for HIFU.
He also received current clinical trial funding from Trod Medical and
Sophiris Biocorp. He is previous Consultant for protocol writing at
Steba Biotech and is current Consultant for protocol writing for Exact
Imaging. He previously received resources from Angiodynamics Inc.
through free device and probe use within investigator-led clinical
trial. At present, he received resources from Hitachi through free probe
use within investigator led clinical trial. Samir S. Taneja is a paid
consultant to Hitachi-Aloka and a study investigator for Steba-Biotech
and Trod Medical. He received funding from Biobot and Hitachi-Aloka. The
remaining authors declare that they have no relevant financial
interests.
NR 27
TC 6
Z9 6
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0090-4295
EI 1527-9995
J9 UROLOGY
JI Urology
PD FEB
PY 2016
VL 88
BP 8
EP 13
DI 10.1016/j.urology.2015.11.018
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA DI4IW
UT WOS:000373464600006
PM 26621480
ER
PT J
AU Anez, G
Heisey, DAR
Chancey, C
Fares, RCG
Espina, LM
Souza, KPR
Teixeira-Carvalho, A
Krysztof, DE
Foster, GA
Stramer, SL
Rios, M
AF Anez, German
Heisey, Daniel A. R.
Chancey, Caren
Fares, Rafaelle C. G.
Espina, Luz M.
Souza, Katia P. R.
Teixeira-Carvalho, Andrea
Krysztof, David E.
Foster, Gregory A.
Stramer, Susan L.
Rios, Maria
TI Distribution of Dengue Virus Types 1 and 4 in Blood Components from
Infected Blood Donors from Puerto Rico
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID TRANSFUSION-TRANSMITTED DENGUE; HEPATITIS-C VIRUS; TRANSPLANT
RECIPIENTS; HEMORRHAGIC-FEVER; DISEASE SEVERITY; WEST; VIREMIA; RNA;
TRANSMISSION; SEROTYPE
AB Background
Dengue is a mosquito-borne viral disease caused by the four dengue viruses (DENV-1 to 4) that can also be transmitted by blood transfusion and organ transplantation. The distribution of DENV in the components of blood from infected donors is poorly understood.
Methods
We used an in-house TaqMan qRT-PCR assay to test residual samples of plasma, cellular components of whole blood (CCWB), serum and clot specimens from the same collection from blood donors who were DENV-RNA-reactive in a parallel blood safety study. To assess whether DENV RNA detected by TaqMan was associated with infectious virus, DENV infectivity in available samples was determined by culture in mosquito cells.
Results
DENV RNA was detected by TaqMan in all tested blood components, albeit more consistently in the cellular components; 78.8% of CCWB, 73.3% of clots, 86.7% of sera and 41.8% of plasma samples. DENV-1 was detected in 48 plasma and 97 CCWB samples while DENV-4 was detected in 21 plasma and 31 CCWB samples. In mosquito cell cultures, 29/111 (26.1%) plasma and 32/97 (32.7%) CCWB samples were infectious. A subset of samples from 29 donors was separately analyzed to compare DENV viral loads in the available blood components. DENV viral loads did not differ significantly between components and ranged from 3-8 log(10) PCR-detectable units/ml.
Conclusions
DENV was present in all tested components from most donors, and viral RNA was not preferentially distributed in any of the tested components. Infectious DENV was also present in similar proportions in cultured plasma, clot and CCWB samples, indicating that these components may serve as a resource when sample sizes are limited. However, these results suggest that the sensitivity of the nucleic acid tests (NAT) for these viruses would not be improved by testing whole blood or components other than plasma.
C1 [Anez, German; Heisey, Daniel A. R.; Chancey, Caren; Fares, Rafaelle C. G.; Espina, Luz M.; Souza, Katia P. R.; Teixeira-Carvalho, Andrea; Rios, Maria] US FDA, Silver Spring, MD USA.
[Krysztof, David E.; Foster, Gregory A.; Stramer, Susan L.] Amer Red Cross, Gaithersburg, MD USA.
[Anez, German] Sanofi Pasteur, Swiftwater, PA USA.
[Heisey, Daniel A. R.] Virginia Commonwealth Univ, Richmond, VA USA.
[Espina, Luz M.] Univ Zulia, Maracaibo 4011, Venezuela.
[Souza, Katia P. R.] Fundacao Oswaldo Cruz FIOCRUZ, Rio De Janeiro, Brazil.
[Teixeira-Carvalho, Andrea] Fundacao Oswaldo Cruz FIOCRUZ, Ctr Pesquisas Rene Rachou, Belo Horizonte, MG, Brazil.
RP Rios, M (reprint author), US FDA, Silver Spring, MD USA.
EM maria.rios@fda.hhs.gov
OI Anez, German/0000-0001-5361-3001
FU United States Food and Drug Administration, Center for Biologics
Evaluation and Research; Conselho Nacional de Desenvolvimento Cientifico
e Tecnologico (CNPq)
FX This study was internally funded by the United States Food and Drug
Administration, Center for Biologics Evaluation and Research. This
project was supported in part by appointments (DARH, CC, LME, KPRS, ATC)
to the Research Participation Program at the Office of Blood Research
and Review, Center for Biologics Evaluation and Research, U.S. Food and
Drug Administration, administered by the Oak Ridge Institute for Science
and Education through an interagency agreement between the U.S.
Department of Energy and F.D.A. ATC thanks Conselho Nacional de
Desenvolvimento Cientifico e Tecnologico (CNPq) for the fellowship (PQ).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 46
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U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD FEB
PY 2016
VL 10
IS 2
AR e0004445
DI 10.1371/journal.pntd.0004445
PG 17
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DH1TH
UT WOS:000372567300053
PM 26871560
ER
PT J
AU Kerlin, R
Bolon, B
Burkhardt, J
Francke, S
Greaves, P
Meador, V
Popp, J
AF Kerlin, Roy
Bolon, Brad
Burkhardt, John
Francke, Sabine
Greaves, Peter
Meador, Vince
Popp, James
TI Scientific and Regulatory Policy Committee: Recommended ("Best")
Practices for Determining, Communicating, and Using Adverse Effect Data
from Nonclinical Studies
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE adversity; NOAEL; nonclinical; risk assessment; toxicity study
ID BENCHMARK DOSE APPROACH; BEAGLE DOGS; TOXICITY; NOAEL; TOXICOLOGY;
CHEMICALS; ANIMALS; HUMANS; RATS
AB Recommendations (best practices) are provided by the Society of Toxicologic Pathology's Adversity Working Group for making consistent interpretations of test article-related effects as adverse and assigning a no observed adverse effect level (NOAEL) in nonclinical toxicity studies. Adverse is a term indicating harm to the test animal, while nonadverse indicates lack of harm. Adverse findings in the study reports should be defined in relation to effects on the test species used and within the context of the given study. Test article-related effects should be described on their own merits, and decisions to consider them as adverse or nonadverse should be justified. Related effects may be discussed together; in particular, markers of toxicity that are not in and of themselves adverse ideally should be discussed in conjunction with the causal toxicity to determine adversity. Adverse findings should be identified in subreports (clinical data, pathology data, etc.) if sufficient information is available, and/or in the final study report as individual or grouped findings, but study NOAELs should be established at the level of the overall study report. Interpretations such as not biologically relevant or not toxicologically important should be avoided unless defined and supported by scientific rationale. Decisions defining adverse findings and the NOAEL in final study reports should combine the expertise of all contributing scientific disciplines. Where possible, use of NOAELs in data tables should be linked to explanatory text that places them in context. Ideally, in nonclinical summary documents, NOAELs from multiple studies are considered together in defining the most important adverse responses in the most sensitive species. These responses are then considered along with an understanding of their likely mechanisms, as well as other information such as variability in species sensitivity, comparative pathology, reversibility and progression, kinetics, and metabolism of the test substance to help assess human risk.
C1 [Kerlin, Roy] Pfizer Worldwide Res & Dev, Drug Safety Res & Dev, Groton, CT 06340 USA.
[Bolon, Brad] GEMpath Inc, Longmont, CO USA.
[Burkhardt, John] AbbVie Res & Dev, Preclin Safety, N Chicago, IL USA.
[Francke, Sabine] US FDA, CFSAN, College Pk, MD USA.
[Greaves, Peter] Leicester Royal Infirm, Dept Canc Studies, Leicester, Leics, England.
[Meador, Vince] Covance Labs Inc, Madison, WI USA.
[Popp, James] Stratoxon LLC, Lancaster, PA USA.
RP Kerlin, R (reprint author), Pfizer Worldwide Res & Dev, Drug Safety Res & Dev, Groton, CT 06340 USA.
EM roy.l.kerlin@pfizer.com
FU Society of Toxicologic Pathology
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This
document was sponsored and is supported by the Society of Toxicologic
Pathology and is endorsed by other professional organizations involved
with toxicologic pathology, including The American College of Veterinary
Pathologists, The American Society for Veterinary Clinical Pathology,
Societe Francaise de Pathologie Toxicologique'' (French Society of
Toxicologic Pathology), The British Society of Toxicologic Pathology,
The European Society of Toxicologic Pathology, The Japanese Society of
Toxicologic Pathology, and The American College of Toxicology).
NR 40
TC 4
Z9 4
U1 1
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
EI 1533-1601
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD FEB
PY 2016
VL 44
IS 2
BP 147
EP 162
DI 10.1177/0192623315623265
PG 16
WC Pathology; Toxicology
SC Pathology; Toxicology
GA DH0KL
UT WOS:000372473000002
PM 26704930
ER
PT J
AU Wang, W
Alvarado-Facundo, E
Chen, Q
Anderson, CM
Scott, D
Vassell, R
Weiss, CD
AF Wang, Wei
Alvarado-Facundo, Esmeralda
Chen, Qiong
Anderson, Christine M.
Scott, Dorothy
Vassell, Russell
Weiss, Carol D.
TI Serum Samples From Middle-aged Adults Vaccinated Annually with Seasonal
Influenza Vaccines Cross-neutralize Some Potential Pandemic Influenza
Viruses
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE cross-neutralization; influenza vaccines; neutralizing antibodies;
pandemic influenza; stem antibodies
ID REACTIVE ANTIBODY-RESPONSES; H2N2; H3; H1; H5
AB We examined serum samples from adults ages 48-64 who received multiple seasonal influenza vaccines from 2004 to 2009 for cross-neutralizing antibodies to potential pandemic strains. Using pseudoviruses bearing various hemagglutinins (HA-pseudoviruses), we found serum neutralization titers (>= 160) in 100% against A/Japan/305/1957 (H2N2), 53% against A/Hong Kong/1073/99 (H9N2), 56% against the H3N2 variant A/Indiana/08/11 (H3N2v), 11% against A/Hong Kong/G9/97 (H9N2), and 36% A/chicken/Hong Kong/SF4/01 (H6N1). None had titers >160 to A/Shanghai/2/13 (H7N9) or A/Netherlands/219/03 (H7N7). Thirty-six percent to 0% had neutralization titers to various H5N1 strains. Titers to H9, H6, and H5 HA-pseudoviruses correlated with each other, but not with H3N2v, suggesting group-specific cross-neutralization.
C1 [Wang, Wei; Alvarado-Facundo, Esmeralda; Chen, Qiong; Vassell, Russell; Weiss, Carol D.] US FDA, Div Viral Prod, Lab Immunoregulat, Silver Spring, MD 20993 USA.
[Anderson, Christine M.; Scott, Dorothy] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Silver Spring, MD 20993 USA.
RP Weiss, CD (reprint author), US FDA, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave,WO Bldg 72,Rm 1214, Silver Spring, MD 20993 USA.
EM carol.weiss@fda.hhs.gov
FU US Food and Drug Administration
FX This work was supported by institutional funds from the US Food and Drug
Administration.
NR 15
TC 1
Z9 1
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD FEB 1
PY 2016
VL 213
IS 3
BP 403
EP 406
DI 10.1093/infdis/jiv407
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DG9XB
UT WOS:000372436000011
PM 26243315
ER
PT J
AU Lapteva, L
Pariser, AR
AF Lapteva, Larissa
Pariser, Anne R.
TI Investigational New Drug applications: a 1-year pilot study on rates and
reasons for clinical hold
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Article
DE Rare Diseases; Drugs; Investigational; Clinical Research
AB Background The Food and Drug Administration (FDA)'s Center for Drug Evaluation and Research (CDER) receives about 1500 initial Investigational New Drug applications (INDs) per year. In the first 30days after initial IND submission, FDA conducts a review to determine whether the proposed investigation is safe to proceed, and if not, the IND may be placed on clinical hold.
Methods A retrospective study of rates and reasons for clinical hold for all initial INDs submitted to CDER in fiscal year (FY) 2013 was performed. INDs were assessed for reasons that led to clinical hold, included chemistry, manufacturing and controls (CMC), animal toxicology or clinical issues. INDs were further categorized by commercial versus research sponsorship, and rare versus common disease indications. All INDs placed on hold were reassessed by whether they remained on hold within the first year following hold imposition.
Results CDER received 1410 initial INDs in FY 2013, of which 125 (8.9%) were placed on hold during the first 30days after initial submission. Of the INDs placed on hold, more than half became active within the first year after first imposition of hold. CMC reasons were most commonly cited, followed by clinical, then toxicology reasons. There were no substantive differences in rates and reasons for hold between INDs for rare or common disease indications, or between commercial or research INDs.
Conclusions The vast majority of initial INDs moved forward within 30days after submission, and for those applications placed on hold, most became active within 1year. The findings also suggest that many holds for new drug product programs can be avoided by following the available guidelines for investigational product development.
C1 [Lapteva, Larissa] US FDA, Div Therapeut Performance, Off Res & Stand, Off Gener Drugs,CDER, Silver Spring, MD USA.
[Pariser, Anne R.] US FDA, Off Translat Sci, CDER, 10903 New Hampshire Ave,WO21-4607, Silver Spring, MD 20993 USA.
RP Pariser, AR (reprint author), US FDA, Off Translat Sci, CDER, 10903 New Hampshire Ave,WO21-4607, Silver Spring, MD 20993 USA.
EM anne.pariser@fda.hhs.gov
NR 9
TC 0
Z9 0
U1 2
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1081-5589
EI 1708-8267
J9 J INVEST MED
JI J. Invest. Med.
PD FEB
PY 2016
VL 64
IS 2
BP 376
EP 382
DI 10.1136/jim-2015-000010
PG 7
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA DG6FX
UT WOS:000372179700005
PM 26911627
ER
PT J
AU Kluetz, PG
Pazdur, R
AF Kluetz, Paul G.
Pazdur, Richard
TI Looking to the future in an unprecedented time for cancer drug
development
SO SEMINARS IN ONCOLOGY
LA English
DT Review
DE Clinical trials; Regulation; Endpoints
ID ONCOLOGY; TRIALS
AB Basic research in cancer biology, genetics and immunology has resulted in improved insights into mechanisms that drive tumor initiation and growth. This improved biologic understanding of the diseases we treat has led to unprecedented therapeutic breakthroughs across multiple tumor types. In this article, we discuss opportunities and. challenges in contemporary cancer drug development, highlighting efficacy endpoints, clinical trial design and the thoughtful inclusion of the patient perspective. As the field re-examines old practices and explores new opportunities, we must continue to efficiently utilize the human and scientific resources at our disposal to foster the development and delivery of safe and effective therapies to cancer patients. Published by Elsevier Inc.
C1 [Kluetz, Paul G.; Pazdur, Richard] US FDA, Off Hematol & Oncol Prod, FDA CDER OND, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
RP Kluetz, PG (reprint author), US FDA, Off Hematol & Oncol Prod, FDA CDER OND, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM Paul.Kluetz@fda.hhs.gov
NR 9
TC 2
Z9 2
U1 1
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
EI 1532-8708
J9 SEMIN ONCOL
JI Semin. Oncol.
PD FEB
PY 2016
VL 43
IS 1
BP 2
EP 3
DI 10.1053/j.seminoncol.2016.01.001
PG 2
WC Oncology
SC Oncology
GA DH3KM
UT WOS:000372685900002
PM 26970117
ER
PT J
AU Gierach, GL
Patel, DA
Pfeiffer, RM
Figueroa, JD
Linville, L
Papathomas, D
Johnson, JM
Chicoine, RE
Herschorn, SD
Shepherd, JA
Wang, J
Malkov, S
Vacek, PM
Weaver, DL
Fan, B
Mahmoudzadeh, AP
Palakal, M
Xiang, J
Oh, H
Horne, HN
Sprague, BL
Hewitt, SM
Brinton, LA
Sherman, ME
AF Gierach, Gretchen L.
Patel, Deesha A.
Pfeiffer, Ruth M.
Figueroa, Jonine D.
Linville, Laura
Papathomas, Daphne
Johnson, Jason M.
Chicoine, Rachael E.
Herschorn, Sally D.
Shepherd, John A.
Wang, Jeff
Malkov, Serghei
Vacek, Pamela M.
Weaver, Donald L.
Fan, Bo
Mahmoudzadeh, Amir Pasha
Palakal, Maya
Xiang, Jackie
Oh, Hannah
Horne, Hisani N.
Sprague, Brian L.
Hewitt, Stephen M.
Brinton, Louise A.
Sherman, Mark E.
TI Relationship of Terminal Duct Lobular Unit Involution of the Breast with
Area and Volume Mammographic Densities
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID CANCER RISK; TISSUE COMPOSITION; FIBROGLANDULAR TISSUE; ASSOCIATION;
AGE; PATTERNS; BIOPSY; WOMEN
AB Elevated mammographic density (MD) is an established breast cancer risk factor. Reduced involution of terminal duct lobular units (TDLU), the histologic source of most breast cancers, has been associated with higher MD and breast cancer risk. We investigated relationships of TDLU involution with area and volumetric MD, measured throughout the breast and surrounding biopsy targets (perilesional). Three measures inversely related to TDLU involution (TDLU count/mm(2), median TDLU span, median acini count/TDLU) assessed in benign diagnostic biopsies from 348 women, ages 40-65, were related to MD area (quantified with thresholding software) and volume (assessed with a density phantom) by analysis of covariance, stratified by menopausal status and adjusted for confounders. Among premenopausal women, TDLU count was directly associated with percent perilesional MD (P trend = 0.03), but not with absolute dense area/volume. Greater TDLU span was associated with elevated percent dense area/volume (P trend<0.05) and absolute perilesionalMD (P = 0.003). Acini count was directly associated with absolute perilesional MD (P = 0.02). Greater TDLU involution (all metrics) was associated with increased nondense area/volume (P trend <= 0.04). Among postmenopausal women, TDLU measures were not significantly associated with MD. Among premenopausal women, reduced TDLU involution was associated with higher area and volumetric MD, particularly in perilesional parenchyma. Data indicating that TDLU involution and MD are correlated markers of breast cancer risk suggest that associations of MD with breast cancer may partly reflect amounts of at-risk epithelium. If confirmed, these results could suggest a prevention paradigm based on enhancing TDLU involution and monitoring efficacy by assessing MD reduction. (C)2015 AACR.
C1 [Gierach, Gretchen L.; Patel, Deesha A.; Figueroa, Jonine D.; Linville, Laura; Papathomas, Daphne; Palakal, Maya; Xiang, Jackie; Oh, Hannah; Horne, Hisani N.; Brinton, Louise A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Chicoine, Rachael E.; Herschorn, Sally D.; Vacek, Pamela M.; Weaver, Donald L.; Sprague, Brian L.] Univ Vermont, Burlington, VT USA.
[Johnson, Jason M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Shepherd, John A.; Wang, Jeff; Malkov, Serghei; Fan, Bo; Mahmoudzadeh, Amir Pasha] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Hewitt, Stephen M.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Sherman, Mark E.] NCI, Breast & Gynecol Canc Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Patel, Deesha A.] Northwestern Univ, Div Gen Internal Med, Feinberg Sch Med, Evanston, IL USA.
[Figueroa, Jonine D.] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Inst Genet & Mol Med, Edinburgh EH8 9YL, Midlothian, Scotland.
[Linville, Laura] George Washington Sch Med & Hlth Studies, Washington, DC USA.
[Wang, Jeff] Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido, Japan.
[Horne, Hisani N.] US FDA, Silver Spring, MD USA.
RP Gierach, GL (reprint author), NCI, 9609 Med Ctr Dr,Rm 7-E108, Bethesda, MD 20892 USA.
EM gierachg@mail.nih.gov
RI Gierach, Gretchen/E-1817-2016;
OI Gierach, Gretchen/0000-0002-0165-5522; Hewitt,
Stephen/0000-0001-8283-1788
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics of the NCI; NCI [U01CA70013, U54CA163303, 1R21CA157254]; Breast
Cancer Research Stamp Funds from the NCI [U01CA70013, U54CA163303,
1R21CA157254]
FX This study was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics of the NCI. Breast Cancer
Research Stamp Funds and cooperative agreement U01CA70013 and
U54CA163303 (to B.M. Geller, P.M. Vacek, D.L. Weaver, R.E. Chicoine,
S.D. Herschorn, and B. Sprague) and 1R21CA157254 (to J.A. Shepherd, S.
Malkov, B. Fan, and A.P. Mahmoudzadeh) from the NCI funded some of the
data collection and image analysis for this study.
NR 39
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Z9 7
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD FEB
PY 2016
VL 9
IS 2
BP 149
EP 158
DI 10.1158/1940-6207.CAPR-15-0282
PG 10
WC Oncology
SC Oncology
GA DG3YC
UT WOS:000372006100006
PM 26645278
ER
PT J
AU Campi-Azevedo, AC
Costa-Pereira, C
Antonelli, LR
Fonseca, CT
Teixeira-Carvalho, A
Villela-Rezende, G
Santos, RA
Batista, MA
Campos, FM
Pacheco-Porto, L
Melo, OA
Hossell, DMSH
Coelho-dos-Reis, JG
Peruhype-Magalhaes, V
Costa-Silva, MF
de Oliveira, JG
Farias, RH
Noronha, TG
Lemos, JA
von Doellinger, VD
Simoes, M
de Souza, MM
Malaquias, LC
Persi, HR
Pereira, JM
Martins, JA
Dornelas-Ribeiro, M
Vinhas, AD
Alves, TR
Maia, MD
Freire, MD
Martins, RD
Homma, A
Romano, APM
Domingues, CM
Tauil, PL
Vasconcelos, PF
Rios, M
Caldas, IR
Camacho, LA
Martins, OA
AF Campi-Azevedo, Ana Carolina
Costa-Pereira, Christiane
Antonelli, Lis R.
Fonseca, Cristina T.
Teixeira-Carvalho, Andrea
Villela-Rezende, Gabriela
Santos, Raiany A.
Batista, Mauricio A.
Campos, Fernanda M.
Pacheco-Porto, Luiza
Melo Junior, Otoni A.
Hossell, Debora M. S. H.
Coelho-dos-Reis, Jordana G.
Peruhype-Magalhaes, Vanessa
Costa-Silva, Matheus F.
de Oliveira, Jaquelline G.
Farias, Roberto H.
Noronha, Tatiana G.
Lemos, Jandira A.
von Doellinger, Vanessa dos R.
Simoes, Marisol
de Souza, Mirian M.
Malaquias, Luiz C.
Persi, Harold R.
Pereira, Jorge M.
Martins, Jose A.
Dornelas-Ribeiro, Marcos
Vinhas, Aline de A.
Alves, Tatiane R.
Maia, Maria de L.
Freire, Marcos da S.
Martins, Reinaldo de M.
Homma, Akira
Romano, Alessandro P. M.
Domingues, Carla M.
Tauil, Pedro L.
Vasconcelos, Pedro F.
Rios, Maria
Caldas, Iramaya R.
Camacho, Luiz A.
Martins-Filho, Olindo Assis
TI Booster dose after 10 years is recommended following 17DD-YF primary
vaccination
SO HUMAN VACCINES & IMMUNOTHERAPEUTICS
LA English
DT Article
DE yellow fever; vaccine; cytokine; flow cytometry; memory cells and
vaccination; duration of immunity
ID YELLOW-FEVER VIRUS; ANTIGEN PRESENTATION; IMMUNE ACTIVATION; CELLS; 17D;
RESPONSES; VACCINES; IMMUNIZATION; ANTIBODIES; INFECTION
AB A single vaccination of Yellow Fever vaccines is believed to confer life-long protection. In this study, results of vaccinees who received a single dose of 17DD-YF immunization followed over 10 y challenge this premise. YF-neutralizing antibodies, subsets of memory T and B cells as well as cytokine-producing lymphocytes were evaluated in groups of adults before (NVday0) and after (PVday30-45, PVyear1-4, PVyear5-9, PVyear10-11, PVyear12-13) 17DD-YF primary vaccination. YF-neutralizing antibodies decrease significantly from PVyear1-4 to PVyear12-13 as compared to PVday30-45, and the seropositivity rates (PRNT2.9Log(10)mIU/mL) become critical (lower than 90%) beyond PVyear5-9. YF-specific memory phenotypes (effector T-cells and classical B-cells) significantly increase at PVday30-45 as compared to naive baseline. Moreover, these phenotypes tend to decrease at PVyear10-11 as compared to PVday30-45. Decreasing levels of TNF-(+) and IFN-(+) produced by CD4(+) and CD8(+) T-cells along with increasing levels of IL-10(+)CD4(+)T-cells were characteristic of anti-YF response over time. Systems biology profiling represented by hierarchic networks revealed that while the naive baseline is characterized by independent micro-nets, primary vaccinees displayed an imbricate network with essential role of central and effector CD8(+) memory T-cell responses. Any putative limitations of this cross-sectional study will certainly be answered by the ongoing longitudinal population-based investigation. Overall, our data support the current Brazilian national immunization policy guidelines that recommend one booster dose 10 y after primary 17DD-YF vaccination.
C1 [Campi-Azevedo, Ana Carolina; Costa-Pereira, Christiane; Antonelli, Lis R.; Fonseca, Cristina T.; Teixeira-Carvalho, Andrea; Villela-Rezende, Gabriela; Santos, Raiany A.; Batista, Mauricio A.; Campos, Fernanda M.; Pacheco-Porto, Luiza; Melo Junior, Otoni A.; Hossell, Debora M. S. H.; Coelho-dos-Reis, Jordana G.; Peruhype-Magalhaes, Vanessa; Costa-Silva, Matheus F.; de Oliveira, Jaquelline G.; Martins-Filho, Olindo Assis] Fiocruz MS, Ctr Pesquisas Rene Rachou, Belo Horizonte, MG, Brazil.
[Farias, Roberto H.; Noronha, Tatiana G.; von Doellinger, Vanessa dos R.; Simoes, Marisol; de Souza, Mirian M.; Freire, Marcos da S.; Martins, Reinaldo de M.] Fiocruz MS, Inst Tecnol Imunobiol Biomanguinhos, Rio De Janeiro, Brazil.
[Lemos, Jandira A.] Governo Estado Minas Gerais, Secretaria Estado Saude, Belo Horizonte, MG, Brazil.
[Malaquias, Luiz C.] Univ Fed Alfenas, Alfenas, MG, Brazil.
[Persi, Harold R.; Pereira, Jorge M.; Martins, Jose A.; Dornelas-Ribeiro, Marcos; Vinhas, Aline de A.; Alves, Tatiane R.] Inst Biol Exercito, Rio De Janeiro, Brazil.
[Maia, Maria de L.; Homma, Akira] Fiocruz MS, Assessoria Clin Biomanguinhos, Rio De Janeiro, Brazil.
[Romano, Alessandro P. M.; Domingues, Carla M.] Minist Saude, Secretaria Vigilancia Saude, Sao Paulo, Brazil.
[Tauil, Pedro L.] Univ Brasilia, BR-70910900 Brasilia, DF, Brazil.
[Vasconcelos, Pedro F.] IEC, Ananindeua, Para, Brazil.
[Rios, Maria] US FDA, CBER, Silver Spring, MD USA.
[Caldas, Iramaya R.] Fiocruz MS, Diretoria Reg Brasilia Direb, Brasilia, DF, Brazil.
[Camacho, Luiz A.] Fiocruz MS, Escola Nacl Saude Publ, Rio De Janeiro, Brazil.
RP Martins, OA (reprint author), Fiocruz MS, Ctr Pesquisas Rene Rachou, Belo Horizonte, MG, Brazil.
EM oamfilho@cpqrr.fiocruz.br
RI Martins, Reinaldo/I-3413-2015
OI Martins, Reinaldo/0000-0002-0667-532X
FU Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG);
Bio-Manguinhos/FIOCRUZ; PROEP/CPqRR/FIOCRUZ; Conselho Nacional de
Desenvolvimento Cientifico e Tecnologico (CNPq); Programa Nacional de
Imunizacoes (PNI) - Ministerio da Saude Brazil; FIOTEC; PDTIS; CAPES;
Secretaria de Vigilancia em Saude (SVS); CNPq MCTI/CNPQ/Universal
[14/2014, 444417/2014-1, 458134/2014-7]; CNPq
FX The authors thank Fundacao de Amparo a Pesquisa do Estado de Minas
Gerais (FAPEMIG), Bio-Manguinhos/FIOCRUZ; PROEP/CPqRR/FIOCRUZ; Conselho
Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Programa
Nacional de Imunizacoes (PNI) - Ministerio da Saude Brazil, FIOTEC,
PDTIS, CAPES and Secretaria de Vigilancia em Saude (SVS) for financial
support. ACCA and JGCdR received financial support from CNPq
MCTI/CNPQ/Universal 14/2014 (ACCA - Grant # 444417/2014-1 and JGCdR -
Grant # 458134/2014-7). OAMF and ATC thank the CNPq for the fellowships
(PQ).
NR 29
TC 3
Z9 3
U1 2
U2 2
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 2164-5515
EI 2164-554X
J9 HUM VACC IMMUNOTHER
JI Human Vaccines Immunother.
PD FEB 1
PY 2016
VL 12
IS 2
BP 491
EP 502
DI 10.1080/21645515.2015.1082693
PG 12
WC Biotechnology & Applied Microbiology; Immunology
SC Biotechnology & Applied Microbiology; Immunology
GA DG0HK
UT WOS:000371745700040
PM 26360663
ER
PT J
AU Silverstein, JS
Casey, BJ
Kofinas, P
Dair, BJ
AF Silverstein, Joshua S.
Casey, Brendan J.
Kofinas, Peter
Dair, Benita J.
TI Protein Adsorption on Chemically Modified Block Copolymer Nanodomains:
Influence of Charge and Flow
SO JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
LA English
DT Article
DE Quartz Crystal Microbalance; Atomic Force Microscopy; Block Copolymer;
Protein Adsorption; Nanopattern
ID QUARTZ-CRYSTAL MICROBALANCE; SELF-ASSEMBLED MONOLAYERS; HYDROPHOBIC
SURFACES; CELL-ADHESION; CONFORMATIONAL-CHANGES; PLASMA-PROTEINS;
SOLID-SURFACES; SERUM-ALBUMIN; ACRYLIC-ACID; IN-SITU
AB Understanding the interactions of biomacromolecules with nanoengineered surfaces is vital for assessing material biocompatibility. This study focuses on the dynamics of protein adsorption on nanopatterned block copolymers (BCPs). Poly(styrene)-block-poly(1,2-butadiene) BCPs functionalized with an acid, amine, amide, or captopril moieties were processed to produce nanopatterned films. These films were characterized using water contact angle measurements and atomic force microscopy in air and liquid to determine how the modification process affected wettability and swelling. Protein adsorption experiments were conducted under static and dynamic conditions via a quartz crystal microbalance with dissipation. Proteins of various size, charge, and stability were investigated to determine whether their physical characteristics affected adsorption. Significantly decreased contact angles were caused by selective swelling of modified BCP domains. The results indicate that nanopatterned chemistry and experimental conditions strongly impact adsorption dynamics. Depending on the structural stability of the protein, polyelectrolyte surfaces significantly increased adsorption over controls. Further analysis suggested that protein stability may correlate with dissipation versus frequency plots.
C1 [Silverstein, Joshua S.; Kofinas, Peter] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA.
[Silverstein, Joshua S.; Casey, Brendan J.; Dair, Benita J.] US FDA, Off Med Prod & Tobacco, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs,Div Chem & Mat Sci, Silver Spring, MD 20993 USA.
RP Dair, BJ (reprint author), US FDA, Off Med Prod & Tobacco, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs,Div Chem & Mat Sci, Silver Spring, MD 20993 USA.
OI Kofinas, Peter/0000-0001-6657-3037
NR 51
TC 0
Z9 0
U1 5
U2 17
PU AMER SCIENTIFIC PUBLISHERS
PI VALENCIA
PA 26650 THE OLD RD, STE 208, VALENCIA, CA 91381-0751 USA
SN 1533-4880
EI 1533-4899
J9 J NANOSCI NANOTECHNO
JI J. Nanosci. Nanotechnol.
PD FEB
PY 2016
VL 16
IS 2
BP 1460
EP 1470
DI 10.1166/jnn.2016.10895
PG 11
WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials
Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA DG8UJ
UT WOS:000372358800033
PM 27433605
ER
PT J
AU Wang, X
Tan, JY
Biswas, S
Zhao, JQ
Devadas, K
Ye, ZP
Hewlett, I
AF Wang, Xue
Tan, Jiying
Biswas, Santanu
Zhao, Jiangqin
Devadas, Krishnakumar
Ye, Zhiping
Hewlett, Indira
TI Pandemic Influenza A (H1N1) Virus Infection Increases Apoptosis and
HIV-1 Replication in HIV-1 Infected Jurkat Cells
SO VIRUSES-BASEL
LA English
DT Article
DE HIV-1; pandemic influenza A (H1N1) virus; apoptosis; CD4; replication
ID RESPIRATORY-DISTRESS-SYNDROME; CRITICALLY-ILL PATIENTS; SYNCYTIUM
FORMATION; A(H1N1) INFECTION; LIPID RAFTS; T-CELLS; H5N1; NEURAMINIDASE;
ACTIVATION; CYTOKINES
AB Influenza virus infection has a significant impact on public health, since it is a major cause of morbidity and mortality. It is not well-known whether influenza virus infection affects cell death and human immunodeficiency virus (HIV)-1 replication in HIV-1-infected patients. Using a lymphoma cell line, Jurkat, we examined the in vitro effects of pandemic influenza A (H1N1) virus (pH1N1) infection on cell death and HIV-1 RNA production in infected cells. We found that pH1N1 infection increased apoptotic cell death through Fas and Bax-mediated pathways in HIV-1-infected Jurkat cells. Infection with pH1N1 virus could promote HIV-1 RNA production by activating host transcription factors including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B), nuclear factor of activated T-cells (NFAT) and activator protein 1 (AP-1) through mitogen-activated protein kinases (MAPK) pathways and T-cell antigen receptor (TCR)-related pathways. The replication of HIV-1 latent infection could be reactivated by pH1N1 infection through TCR and apoptotic pathways. These data indicate that HIV-1 replication can be activated by pH1N1 virus in HIV-1-infected cells resulting in induction of cell death through apoptotic pathways.
C1 [Wang, Xue; Tan, Jiying; Biswas, Santanu; Zhao, Jiangqin; Devadas, Krishnakumar; Hewlett, Indira] US FDA, CBER, Div Emerging & Transfus Transmitted Dis, Mol Virol Lab, Bldg 72,Rm 4322,10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
[Ye, Zhiping] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Silver Spring, MD 20993 USA.
[Tan, Jiying] Lanzhou Univ, Sch Basic Med Sci, Dept Immunol, Lanzhou 730000, Gansu, Peoples R China.
RP Wang, X; Hewlett, I (reprint author), US FDA, CBER, Div Emerging & Transfus Transmitted Dis, Mol Virol Lab, Bldg 72,Rm 4322,10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM xue.wang@fda.hhs.gov; tangjy@lzu.edu.cn; Santanu.biswas@fda.hhs.gov;
Jiangqin.zhao@fda.hhs.gov; Krishnakumar.devada@fda.hhs.gov;
zhiping.ye@fda.hhs.gov; indira.hewlett@fda.hhs.gov
FU internal CBER modernizing science grant
FX The authors wish to acknowledge of Mohan Haleyurgirisetty and Viswanath
Ragupathy for critical review of this manuscript, and acknowledge of the
NIH AIDS reagent repository for the reagents. This work was supported by
an internal CBER modernizing science grant. The findings and conclusions
in this article have not been formally disseminated by the Food and Drug
Administration and should not be construed to represent any Agency
determination or policy.
NR 41
TC 0
Z9 0
U1 3
U2 3
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD FEB
PY 2016
VL 8
IS 2
AR 33
DI 10.3390/v8020033
PG 11
WC Virology
SC Virology
GA DG1MI
UT WOS:000371831800018
ER
PT J
AU Marrone, AK
Tryndyak, V
Beland, FA
Pogribny, IP
AF Marrone, April K.
Tryndyak, Volodymyr
Beland, Frederick A.
Pogribny, Igor P.
TI MicroRNA Responses to the Genotoxic Carcinogens Aflatoxin B-1 and
Benzo[a]pyrene in Human HepaRG Cells
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE HepaRG cells; aflatoxin B1; benzo[a]pyrene; microRNA
ID GENE-EXPRESSION PROFILES; MIR-122 EXPRESSION; HUMAN HEPATOCYTES; CANCER
HAZARDS; LIVER-DISEASE; IDENTIFICATION; CLUSTER; HEPATOCARCINOGENESIS;
BIOASSAY; BINDING
AB Recent advances in toxicogenomics present an opportunity to develop new in vitro testing methodologies to identify human carcinogens. We have investigated microRNA expression responses to the treatment of human liver HepaRG cells with the human genotoxic carcinogens aflatoxin B-1 (AFB1) and benzo[a]pyrene (B[a]P), and the structurally similar compounds aflatoxin B-2 (AFB2) and benzo[e]pyrene (B[e]P) that exhibit minimal carcinogenic potential. We demonstrate that treatment of HepaRG cells with AFB1 or B[a]P resulted in specific changes in the expression of miRNAs as compared with their non-carcinogenic analogues, particularly in a marked over-expression of miR-410. An additional novel finding is the dose-and time-dependent inhibition of miR-122 in AFB1-treated HepaRG cells. Mechanistically, the AFB1-induced down-regulation of miR-122 was attributed to inhibition of the HNF4A/miR-122 regulatory pathway. These results demonstrate that HepaRG cells can be used to investigate miRNA responses to xenobiotic exposure, and illustrate the existence of early non-genotoxic events, in addition to a well-established genotoxic mode of action changes, in the mechanismof AFB1 and B[a]P carcinogenicity.
C1 [Marrone, April K.; Tryndyak, Volodymyr; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA.
RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM igor.pogribny@fda.hhs.gov
NR 44
TC 3
Z9 3
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD FEB
PY 2016
VL 149
IS 2
BP 496
EP 502
DI 10.1093/toxsci/kfv253
PG 7
WC Toxicology
SC Toxicology
GA DF8NF
UT WOS:000371613900022
PM 26609139
ER
PT J
AU Xia, XJ
Wieslander, B
Strauss, DG
Wagner, GS
Zareba, W
Moss, AJ
Couderc, JP
AF Xia, Xiaojuan
Wieslander, Bjorn
Strauss, David G.
Wagner, Galen S.
Zareba, Wojciech
Moss, Arthur J.
Couderc, Jean-Philippe
TI Automatic QRS Selvester scoring system in patients with left bundle
branch block
SO EUROPACE
LA English
DT Article
DE Selvester QRS scoring system; Left bundle branch block;
Electrocardiography
ID CARDIAC-RESYNCHRONIZATION THERAPY; MYOCARDIAL INFARCT SIZE; QUANTITATIVE
ANATOMIC FINDINGS; SCAR; CONDUCTION; QUANTIFICATION; CARDIOMYOPATHY
AB The Selvester QRS scoring system uses quantitative criteria from the standard 12-lead electrocardiogram (ECG) to estimate the myocardial scar size of patients, including those with left bundle branch block (LBBB). Automation of the scoring system could facilitate the clinical use of this technique which requires a set of multiple QRS patterns to be identified and measured.
We developed a series of algorithms to automatically detect and measure the QRS parameters required for Selvester scoring. The 'QUantitative and Automatic REport of Selvester Score' was designed specifically for the analysis of ECGs from patients meeting new strict criteria for complete LBBB. The algorithms were designed using a training (n = 36) and a validation (n = 180) set of ECGs, consisting of signal-averaged 12-lead ECGs (1000 Hz sampling) recorded from 216 LBBB patients from the MADIT-CRT. We assessed the performance of the methods using expert manually adjudicated ECGs. The average of absolute differences between automatic and adjudicated Selvester scoring was 1.2 +/- 1.5 points. The range of average differences for continuous measurements of wave locations and interval durations varied between 0 and 6 ms. Erroneous detection of Q, R, S, R', and S' waves (oversensed or missed) were 3, 1, 1, 16, and 6%, respectively. Seven percent of notches detected in the first 40 ms were misdetected.
We propose an efficient computerized method for the automatic measurement of the Selvester score in patients with the strict LBBB.
C1 [Xia, Xiaojuan; Zareba, Wojciech; Moss, Arthur J.; Couderc, Jean-Philippe] Univ Rochester, Med Ctr, Div Cardiol, Heart Res Follow Up Program, 265 Crittenden Blvd,POB 653, Rochester, NY 14642 USA.
[Wieslander, Bjorn] Karolinska Inst, Clin Physiol, Stockholm, Sweden.
[Wieslander, Bjorn] Karolinska Univ Hosp, Stockholm, Sweden.
[Strauss, David G.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD USA.
[Wagner, Galen S.] Duke Univ, Duke Clin Res Inst, Durham, NC USA.
RP Xia, XJ (reprint author), Univ Rochester, Med Ctr, Div Cardiol, Heart Res Follow Up Program, 265 Crittenden Blvd,POB 653, Rochester, NY 14642 USA.
EM heartjxx@heart.rochester.edu
NR 20
TC 3
Z9 3
U1 1
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1099-5129
EI 1532-2092
J9 EUROPACE
JI Europace
PD FEB 1
PY 2016
VL 18
IS 2
BP 308
EP 314
DI 10.1093/europace/euv040
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DF3LB
UT WOS:000371244400023
PM 25805156
ER
PT J
AU Zaza, S
Koonin, LM
Ajao, A
Nystrom, SV
Branson, R
Patel, A
Bray, B
Iademarco, MF
AF Zaza, Stephanie
Koonin, Lisa M.
Ajao, Adebola
Nystrom, Scott V.
Branson, Richard
Patel, Anita
Bray, Bruce
Iademarco, Michael F.
TI A Conceptual Framework for Allocation of Federally Stockpiled
Ventilators During Large-Scale Public Health Emergencies
SO HEALTH SECURITY
LA English
DT Article
ID MASS CRITICAL-CARE; MECHANICAL VENTILATORS; DEFINITIVE CARE;
CRITICALLY-ILL; UNITED-STATES; JANUARY 26-27; TASK-FORCE; INFLUENZA;
DISASTER; RESOURCES
AB Some types of public health emergencies could result in large numbers of patients with respiratory failure who need mechanical ventilation. Federal public health planning has included needs assessment and stockpiling of ventilators. However, additional federal guidance is needed to assist states in further allocating federally supplied ventilators to individual hospitals to ensure that ventilators are shipped to facilities where they can best be used during an emergency. A major consideration in planning is a hospital's ability to absorb additional ventilators, based on available space and staff expertise. A simple pro rata plan that does not take these factors into account might result in suboptimal use or unused scarce resources. This article proposes a conceptual framework that identifies the steps in planning and an important gap in federal guidance regarding the distribution of stockpiled mechanical ventilators during an emergency.
C1 [Zaza, Stephanie] CDC, Ctr Dis Control & Prevent, Natl Ctr HIV AIDS STD Viral Hepatitis & TB Preven, Div Adolescent & Sch Hlth, Atlanta, GA 30333 USA.
[Zaza, Stephanie; Koonin, Lisa M.] CDC, Off Infect Dis, Influenza Coordinat Unit, Atlanta, GA 30333 USA.
[Ajao, Adebola] US FDA, Off Med Policy Initiat, Div Clin Trials Qual, Silver Spring, MD USA.
[Nystrom, Scott V.] Off Policy & Planning, Div Med Countermeasure Strategy & Requirements, Washington, DC USA.
[Nystrom, Scott V.] Dept Hlth & Human Serv, Preparedness & Response, Washington, DC USA.
[Branson, Richard] Univ Cincinnati, Surg, Cincinnati, OH USA.
[Patel, Anita] CDC, Off Publ Hlth Preparedness & Response, Div Strateg Natl Stockpile, Atlanta, GA 30333 USA.
[Bray, Bruce] Emory Univ Hosp, Dept Resp Care, 1364 Clifton Rd NE, Atlanta, GA 30322 USA.
[Bray, Bruce] Emory Univ Hosp, Dept EKG, 1364 Clifton Rd NE, Atlanta, GA 30322 USA.
[Bray, Bruce] Emory Univ Hosp, Dept Neurophysiol, 1364 Clifton Rd NE, Atlanta, GA 30322 USA.
[Bray, Bruce] Emory Univ Hosp, Dept Pulm Funct & Blood Gas Labs, 1364 Clifton Rd NE, Atlanta, GA 30322 USA.
[Iademarco, Michael F.] CDC, Ctr Surveillance Epidemiol & Lab Serv, Atlanta, GA 30333 USA.
RP Koonin, LM (reprint author), Ctr Dis Control & Prevent, Influenza Coordinat Unit, 1600 Clifton Rd NE,Mailstop A28, Atlanta, GA 30329 USA.
EM lmk1@cdc.gov
NR 32
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 2326-5094
EI 2326-5108
J9 HEALTH SECUR
JI Health Secur.
PD FEB 1
PY 2016
VL 14
IS 1
BP 1
EP 6
DI 10.1089/hs.2015.0043
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DF4QN
UT WOS:000371334800001
PM 26828799
ER
PT J
AU Zusterzeel, R
Selzman, KA
Sanders, WE
O'Callaghan, KM
Canos, DA
Vernooy, K
Prinzen, FW
Gorgels, APM
Strauss, DG
AF Zusterzeel, Robbert
Selzman, Kimberly A.
Sanders, William E.
O'Callaghan, Kathryn M.
Canos, Daniel A.
Vernooy, Kevin
Prinzen, Frits W.
Gorgels, Anton P. M.
Strauss, David G.
TI Toward Sex-Specific Guidelines for Cardiac Resynchronization Therapy?
SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
LA English
DT Article
DE Cardiac resynchronization therapy; Women; Sex; Guidelines; Outcomes
ID BUNDLE-BRANCH-BLOCK; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR;
DYSSYNCHRONOUS HEART-FAILURE; CARDIOVASCULAR DATA REGISTRY;
RANDOMIZED-CONTROLLED-TRIALS; CLINICAL EVENT REDUCTION; QRS MORPHOLOGY;
PR INTERVAL; IMPROVE HF; WOMEN
AB An important treatment for patients with heart failure is cardiac resynchronization therapy (CRT). Even though only 20 % of women were included in clinical trials for CRT, a benefit has been shown in recent studies for subgroups of women compared to their male counterparts. Given this low inclusion rate of women in clinical studies, professional society guideline-based CRT recommendations, such as those by the American College of Cardiology Foundation (ACCF)/American Heart Association (AHA)/Heart Rhythm Society (HRS), may not truly represent the best treatment for women, especially since most of the reports that showed this greater benefit in women were published after the latest guidelines. Despite having research and multiple publications regarding sex-specific heart failure outcomes and response to CRT, the ACCF/AHA/HRS guidelines have not yet been updated to account for the recent information regarding the differences in benefit for women and men with similar patient characteristics. This review discusses the physiology behind CRT, sex-specific characteristics of heart failure, and cardiac electrophysiology and summarizes the current sex-specific literature to encourage consideration of CRT guidelines for women and men separately.
C1 [Zusterzeel, Robbert; Selzman, Kimberly A.; Sanders, William E.; O'Callaghan, Kathryn M.; Canos, Daniel A.; Strauss, David G.] US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
[Zusterzeel, Robbert; Vernooy, Kevin; Prinzen, Frits W.; Gorgels, Anton P. M.] Maastricht Univ, Med Ctr, Dept Cardiol, NL-6200 MD Maastricht, Netherlands.
[Zusterzeel, Robbert] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.
RP Zusterzeel, R (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.; Zusterzeel, R (reprint author), Maastricht Univ, Med Ctr, Dept Cardiol, NL-6200 MD Maastricht, Netherlands.; Zusterzeel, R (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.
EM robbert.zusterzeel@fda.hhs.gov
FU FDA Office of Women's Health; Oak Ridge Institute for Science and
Education
FX This project was supported in part by the FDA Office of Women's Health
and by a research fellowship from the Oak Ridge Institute for Science
and Education through an interagency agreement between the US Department
of Energy and the FDA.
NR 58
TC 0
Z9 0
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1937-5387
EI 1937-5395
J9 J CARDIOVASC TRANSL
JI J. Cardiovasc. Transl. Res.
PD FEB
PY 2016
VL 9
IS 1
BP 12
EP 22
DI 10.1007/s12265-015-9663-z
PG 11
WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental
SC Cardiovascular System & Cardiology; Research & Experimental Medicine
GA DF3OV
UT WOS:000371255100003
PM 26659647
ER
PT J
AU Tryndyak, VP
Marrone, AK
Latendresse, JR
Muskhelishvili, L
Beland, FA
Pogribny, IP
AF Tryndyak, Volodymyr P.
Marrone, April K.
Latendresse, John R.
Muskhelishvili, Levan
Beland, Frederick A.
Pogribny, Igor P.
TI MicroRNA changes, activation of progenitor cells and severity of liver
injury in mice induced by choline and folate deficiency
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE Liver injury; Methyl-donor deficient diet; Mouse; MicroRNA; Progenitor
cells
ID HEPATOCYTE-LIKE CELLS; EMBRYONIC STEM-CELLS; NONALCOHOLIC
STEATOHEPATITIS; INTERSTRAIN DIFFERENCES; DUCTULAR REACTION;
NATURAL-HISTORY; DISEASE; EXPRESSION; FIBROSIS; DIET
AB Dietary deficiency in methyl-group donors and cofactors induces liver injury that resembles many pathophysiological and histopathological features of human nonalcoholic fatty liver disease (NAFLD), including an altered expression of microRNAs (miRNAs). We evaluated the consequences of a choline- and folate-deficient (CFD) diet on the expression of miRNAs in the livers of male A/J and WSB/EiJ mice. The results demonstrate that NAFLD-like liver injury induced by the CFD diet in A/J and WSB/EiJ mice was associated with marked alterations in hepatic miRNAome profiles, with the magnitude of miRNA expression changes being greater in WSB/EiJ mice, the strain characterized by the greatest severity of liver injury. Specifically, WSB/EiJ mice exhibited more prominent changes in the expression of common miRNAs as compared to A/J mice and distinct miRNA alterations, including the overexpression of miR-134, miR-409-3p, miR-410 and miR-495 miRNAs that were accompanied by an activation of hepatic progenitor cells and fibrogenesis. This in vivo finding was further confirmed by in vitro experiments showing an overexpression of these miRNAs in undifferentiated progenitor hepatic HepaRG cells compared to in fully differentiated HepaRG cells. Additionally, a marked elevation of miR-134, miR-409-3p, miR-410 and miR-495 was found in plasma of WSB/EiJ mice fed the CFD diet, while none of the miRNAs was changed in plasma of A/J mice. These findings suggest that miRNAs may be crucial regulators responsible for the progression of NAFLD and may be useful as noninvasive diagnostic indicators of the severity and progression of NAFLD. Published by Elsevier Inc.
C1 [Tryndyak, Volodymyr P.; Marrone, April K.; Beland, Frederick A.; Pogribny, Igor P.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Latendresse, John R.; Muskhelishvili, Levan] US FDA, Toxicol Pathol Associates, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM igor.pogribny@fda.hhs.gov
NR 50
TC 2
Z9 2
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
EI 1873-4847
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD FEB
PY 2016
VL 28
BP 83
EP 90
DI 10.1016/j.jnutbio.2015.10.001
PG 8
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA DF4YS
UT WOS:000371359100009
PM 26878785
ER
PT J
AU Everett, KD
Conway, C
Desany, GJ
Baker, BL
Choi, G
Taylor, CA
Edelman, ER
AF Everett, Kay D.
Conway, Claire
Desany, Gerard J.
Baker, Brian L.
Choi, Gilwoo
Taylor, Charles A.
Edelman, Elazer R.
TI Structural Mechanics Predictions Relating to Clinical Coronary Stent
Fracture in a 5 Year Period in FDA MAUDE Database
SO ANNALS OF BIOMEDICAL ENGINEERING
LA English
DT Article
DE Stent fracture; Arterial deformation; Finite element analysis
ID SIROLIMUS-ELUTING STENT; SUPERFICIAL FEMORAL-ARTERY; BALLOON-EXPANDABLE
STENTS; FINITE-ELEMENT-ANALYSIS; FATIGUE LIFE; IMPLANTATION; IMPACT;
STRESSES; DESIGN; SHAPE
AB Endovascular stents are the mainstay of interventional cardiovascular medicine. Technological advances have reduced biological and clinical complications but not mechanical failure. Stent strut fracture is increasingly recognized as of paramount clinical importance. Though consensus reigns that fractures can result from material fatigue, how fracture is induced and the mechanisms underlying its clinical sequelae remain ill-defined. In this study, strut fractures were identified in the prospectively maintained Food and Drug Administration's (FDA) Manufacturer and User Facility Device Experience Database (MAUDE), covering years 2006-2011, and differentiated based on specific coronary artery implantation site and device configuration. These data, and knowledge of the extent of dynamic arterial deformations obtained from patient CT images and published data, were used to define boundary conditions for 3D finite element models incorporating multimodal, multi-cycle deformation. The structural response for a range of stent designs and configurations was predicted by computational models and included estimation of maximum principal, minimum principal and equivalent plastic strains. Fatigue assessment was performed with Goodman diagrams and safe/unsafe regions defined for different stent designs. Von Mises stress and maximum principal strain increased with multimodal, fully reversed deformation. Spatial maps of unsafe locations corresponded to the identified locations of fracture in different coronary arteries in the clinical database. These findings, for the first time, provide insight into a potential link between patient adverse events and computational modeling of stent deformation. Understanding of the mechanical forces imposed under different implantation conditions may assist in rational design and optimal placement of these devices.
C1 [Everett, Kay D.; Conway, Claire; Edelman, Elazer R.] MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Desany, Gerard J.; Baker, Brian L.] US FDA, Winchester Engn & Analyt Ctr, Winchester, MA USA.
[Choi, Gilwoo; Taylor, Charles A.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
[Edelman, Elazer R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
RP Conway, C (reprint author), MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM kfurman@mit.edu; cconway@mit.edu; Gerard.Desany@fda.hhs.gov;
Brian.Baker@fda.hhs.gov; giroo@heartflow.com; taylor@heartflow.com;
ere@mit.edu
OI /0000-0003-4236-2280
FU FDA Office of Regulatory Affairs; National Institute of Health [R01
GM49039]
FX This work was funded in part by Grants from FDA Office of Regulatory
Affairs, R01 GM49039 (ERE) from the National Institute of Health, and
appointment to the Research Participation Program at FDA administered by
Oak Ridge Institute for Science and Education (CC).
NR 52
TC 3
Z9 3
U1 3
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0090-6964
EI 1573-9686
J9 ANN BIOMED ENG
JI Ann. Biomed. Eng.
PD FEB
PY 2016
VL 44
IS 2
BP 391
EP 403
DI 10.1007/s10439-015-1476-3
PG 13
WC Engineering, Biomedical
SC Engineering
GA DF0RJ
UT WOS:000371046300011
PM 26467552
ER
PT J
AU Saylor, DM
Forrey, C
Kim, CS
Warren, JA
AF Saylor, David M.
Forrey, Christopher
Kim, Chang-Soo
Warren, James A.
TI Diffuse Interface Methods for Modeling Drug-Eluting Stent Coatings
SO ANNALS OF BIOMEDICAL ENGINEERING
LA English
DT Article
DE Microstructure; Thermodynamics; Diffusion; Simulation; Controlled
release
ID SOLVENT SYSTEMS; SELF-DIFFUSION; POLYMER; COEFFICIENTS; ARTERIAL;
DELIVERY; RELEASE; TETRAHYDROFURAN; THERMODYNAMICS; SIMULATION
AB An overview of diffuse interface models specific to drug-eluting stent coatings is presented. Microscale heterogeneities, both in the coating and use environment, dictate the performance of these coatings. Using diffuse interface methods, these heterogeneities can be explicitly incorporated into the model equations with relative ease. This enables one to predict the complex microstructures that evolve during coating fabrication and subsequent impact on drug release. Examples are provided that illustrate the wide range of phenomena that can be addressed with diffuse interface models including: crystallization, constrained phase separation, hydrolytic degradation, and heterogeneous binding. Challenges associated with the lack of material property data and numerical solution of the model equations are also highlighted. Finally, in light of these potential drawbacks, the potential to utilize diffuse interface models to help guide product and process development is discussed.
C1 [Saylor, David M.; Forrey, Christopher] US FDA, Silver Spring, MD 20993 USA.
[Kim, Chang-Soo] Univ Wisconsin, Milwaukee, WI 53211 USA.
[Warren, James A.] NIST, Gaithersburg, MD 20899 USA.
RP Saylor, DM (reprint author), US FDA, Silver Spring, MD 20993 USA.
EM david.saylor@fda.hhs.gov
NR 44
TC 1
Z9 1
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0090-6964
EI 1573-9686
J9 ANN BIOMED ENG
JI Ann. Biomed. Eng.
PD FEB
PY 2016
VL 44
IS 2
BP 548
EP 559
DI 10.1007/s10439-015-1375-7
PG 12
WC Engineering, Biomedical
SC Engineering
GA DF0RJ
UT WOS:000371046300024
PM 26183961
ER
PT J
AU Kishnani, PS
Dickson, PI
Muldowney, L
Lee, JJ
Rosenberg, A
Abichandani, R
Bluestone, JA
Burton, BK
Dewey, M
Freitas, A
Gavin, D
Griebel, D
Hogan, M
Holland, S
Tanpaiboon, P
Turka, LA
Utz, JJ
Wang, YM
Whitley, CB
Kazi, ZB
Pariser, AR
AF Kishnani, Priya S.
Dickson, Patricia I.
Muldowney, Laurie
Lee, Jessica J.
Rosenberg, Amy
Abichandani, Rekha
Bluestone, Jeffrey A.
Burton, Barbara K.
Dewey, Maureen
Freitas, Alexandra
Gavin, Derek
Griebel, Donna
Hogan, Melissa
Holland, Stephen
Tanpaiboon, Pranoot
Turka, Laurence A.
Utz, Jeanine J.
Wang, Yow-Ming
Whitley, Chester B.
Kazi, Zoheb B.
Pariser, Anne R.
TI Immune response to enzyme replacement therapies in lysosomal storage
diseases and the role of immune tolerance induction
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Review
DE Immune tolerance; Lysosomal storage diseases; Enzyme replacement
therapy; Inborn errors of metabolism; Neutralizing antibodies; Orphan
drugs; Rare diseases
ID INFANTILE POMPE DISEASE; FABRY-DISEASE; MUCOPOLYSACCHARIDOSIS-I;
INTRAVENOUS IMMUNOGLOBULIN; NEUTRALIZING ANTIBODIES; CLINICAL-OUTCOMES;
AGALSIDASE-ALPHA; DISORDERS; EFFICACY; SAFETY
AB The US Food and Drug Administration (FDA) and National Organization for Rare Disease (NORD) convened a public workshop titled "Immune Responses to Enzyme Replacement Therapies: Role of Immune Tolerance Induction" to discuss the impact of anti-drug antibodies (ADAs) on efficacy and safety of enzyme replacement therapies (ERTs) intended to treat patients with lysosomal storage diseases (LSDs). Participants in the workshop included FDA staff, clinicians, scientists, patients, industry, and advocacy group representatives. The risks and benefits of implementing prophylactic immune tolerance induction (ITI) to reduce the potential clinical impact of antibody development were considered. Complications due to immune responses to ERT are being recognized with increasing experience and lengths of exposure to ERTs to treat several LSDs. Strategies to mitigate immune responses and to optimize therapies are needed. Discussions during the workshop resulted in the identification of knowledge gaps and future areas of research, as well as the following proposals from the participants: (1) systematic collection of longitudinal data on immunogenicity to better understand the impact of ADAs on long-term clinical outcomes; (2) development of disease-specific biomarkers and outcome measures to assess the effect of ADAs and ITI on efficacy and safety; (3) development of consistent approaches to ADA assays to allow comparisons of immunogenicity data across different products and disease groups, and to expedite reporting of results; (4) establishment of a system to widely share data on antibody titers following treatment with ERTs; (5) identification of components of the protein that are immunogenic so that triggers and components of the immune responses can be targeted in ITI; and (6) consideration of early ITI in patients who are at risk of developing clinically relevant ADA that have been demonstrated to worsen treatment outcomes. Published by Elsevier Inc.
C1 [Kishnani, Priya S.; Kazi, Zoheb B.] Duke Univ, Med Ctr, Dept Pediat, Div Med Genet, Durham, NC 27710 USA.
[Dickson, Patricia I.] Harbor UCLA Med Ctr, Div Med Genet, Los Angeles Biomed Res Inst, Torrance, CA 90505 USA.
[Muldowney, Laurie; Lee, Jessica J.; Dewey, Maureen; Griebel, Donna] US FDA, Div Gastroenterol & Inborn Errors Metab Prod, Off New Drugs, CDER, Silver Spring, MD 20993 USA.
[Rosenberg, Amy] US FDA, Div Therapeut Proteins, Off Biotechnol Prod, CDER, Silver Spring, MD 20993 USA.
[Abichandani, Rekha] Shire, Lexington, MA 02421 USA.
[Bluestone, Jeffrey A.] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
[Burton, Barbara K.] Northwestern Univ, Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp, Chicago, IL 60611 USA.
[Freitas, Alexandra; Gavin, Derek] Natl Org Rare Disorders, Washington, DC 20036 USA.
[Hogan, Melissa] Saving Case & Friends Inc, Thompsons Stn, TN 37179 USA.
[Holland, Stephen] Natl MPS Soc, Durham, NC 27709 USA.
[Tanpaiboon, Pranoot] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Turka, Laurence A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Transplantat Sci, Boston, MA 02129 USA.
[Utz, Jeanine J.; Whitley, Chester B.] Univ Minnesota, Masonic Childrens Hosp, Minneapolis, MN 55455 USA.
[Wang, Yow-Ming] US FDA, Div Clin Pharmacol 3, Off Clin Pharmacol, OTS,CDER, Silver Spring, MD 20993 USA.
[Pariser, Anne R.] US FDA, OTS, CDER, 10903 New Hampshire Ave,W021-4607, Silver Spring, MD 20993 USA.
RP Pariser, AR (reprint author), US FDA, OTS, CDER, 10903 New Hampshire Ave,W021-4607, Silver Spring, MD 20993 USA.
EM priya.kishnani@duke.edu; pdickson@labiomed.org;
laurie.muldowney@fda.hhs.gov; jessica.j.lee@fda.hhs.gov;
amy.rosenberg@fda.hhs.gov; rabichan@shire.com; jeff.bluestone@ucsf.edu;
bburton@luriechildrens.org; maureen.dewey@fda.hhs.gov;
afreitas@rarediseases.org; dgavin@rarediseases.org;
donna.griebel@fda.hhs.gov; melissa@savingcase.com;
steve.holland@thomsonreuters.com; ptanpaib@childrensnational.org;
lturka@partners.org; utz002@umn.edu; yowming.wang@fda.hhs.gov;
whitley@umn.edu; zoheb.kazi@dm.duke.edu; anne.pariser@fda.hhs.gov
OI Kazi, Zoheb/0000-0002-0447-2764
FU NIAID NIH HHS [R01 AI046643]
NR 56
TC 2
Z9 2
U1 1
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2016
VL 117
IS 2
BP 66
EP 83
DI 10.1016/j.ymgme.2015.11.001
PG 18
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA DE8LS
UT WOS:000370888100341
PM 26597321
ER
PT J
AU Li, CH
Bies, RR
Wang, Y
Sharma, MR
Karovic, S
Werk, L
Edelman, MJ
Miller, AA
Vokes, EE
Oto, A
Ratain, MJ
Schwartz, LH
Maitland, ML
AF Li, C. H.
Bies, R. R.
Wang, Y.
Sharma, M. R.
Karovic, S.
Werk, L.
Edelman, M. J.
Miller, A. A.
Vokes, E. E.
Oto, A.
Ratain, M. J.
Schwartz, L. H.
Maitland, M. L.
TI Comparative Effects of CT Imaging Measurement on RECIST End Points and
Tumor Growth Kinetics Modeling
SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE
LA English
DT Article
DE tomography; x-ray computed; humans; models; statistical; Response
Evaluation Criteria in Solid Tumors; lung neoplasms; drug therapy;
clinical trials; antineoplastic agents; pharmacology
ID CELL-LUNG-CANCER; LEUKEMIA GROUP-B; PHASE-II; CLINICAL-TRIALS; DRUG
DEVELOPMENT; DECISION-MAKING; SOLID TUMORS; SURVIVAL; ONCOLOGY; PREDICT
AB Quantitative assessments of tumor burden and modeling of longitudinal growth could improve phase II oncology trials. To identify obstacles to wider use of quantitative measures we obtained recorded linear tumor measurements from three published lung cancer trials. Model-based parameters of tumor burden change were estimated and compared with similarly sized samples from separate trials. Time-to-tumor growth (TTG) was computed from measurements recorded on case report forms and a second radiologist blinded to the form data. Response Evaluation Criteria in Solid Tumors (RECIST)-based progression-free survival (PFS) measures were perfectly concordant between the original forms data and the blinded radiologist re-evaluation (intraclass correlation coefficient = 1), but these routine interrater differences in the identification and measurement of target lesions were associated with an average 18-week delay (range, -20 to 55 weeks) in TTG (intraclass correlation coefficient = 0.32). To exploit computational metrics for improving statistical power in small clinical trials will require increased precision of tumor burden assessments.
C1 [Li, C. H.; Bies, R. R.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Li, C. H.; Bies, R. R.] Indiana Clin & Translat Sci Inst CTSI, Indianapolis, IN USA.
[Bies, R. R.; Sharma, M. R.; Werk, L.; Edelman, M. J.; Miller, A. A.; Vokes, E. E.; Oto, A.; Ratain, M. J.; Schwartz, L. H.; Maitland, M. L.] Alliance Clin Trials Oncol, Boston, MA USA.
[Wang, Y.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA.
[Sharma, M. R.; Karovic, S.; Vokes, E. E.; Oto, A.; Ratain, M. J.; Maitland, M. L.] Univ Chicago Med & Biol Sci, Chicago, IL USA.
[Werk, L.] Duke Univ, Durham, NC USA.
[Edelman, M. J.] Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Miller, A. A.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Schwartz, L. H.] Columbia Univ, Coll Phys & Surg, New York, NY USA.
RP Maitland, ML (reprint author), Alliance Clin Trials Oncol, Boston, MA USA.; Maitland, ML (reprint author), Univ Chicago Med & Biol Sci, Chicago, IL USA.
EM mmaitlan@medicine.bsd.uchicago.edu
FU NIH [K23CA124802, U10CA031946, R01CA194783]; Indiana CTSI from Eli Lilly
and Company
FX Support for this study was provided by NIH K23CA124802 (Career
Development Award to M.L.M.), NIH U10CA031946 (Cancer and Leukemia Group
B Chair's Development Project to M.L.M. and L.H.S.), NIH R01CA194783 (to
M.L.M. and L.H.S.), and The Indiana CTSI through a gift from Eli Lilly
and Company (C.H.L. and R.R.B.). The authors are grateful to Thomas
Yaeger for technical assistance and Dr. Valerie Andre for expert
guidance on tumor growth modeling.
NR 39
TC 2
Z9 2
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1752-8054
EI 1752-8062
J9 CTS-CLIN TRANSL SCI
JI CTS-Clin. Transl. Sci.
PD FEB
PY 2016
VL 9
IS 1
BP 43
EP 50
DI 10.1111/cts.12384
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DE5AD
UT WOS:000370641400007
PM 26790562
ER
PT J
AU Luo, JJ
Rasooly, A
Wang, LQ
Zeng, K
Shen, CC
Qian, P
Yang, MH
Qu, FL
AF Luo, Junjun
Rasooly, Avraham
Wang, Liqiang
Zeng, Ke
Shen, Congcong
Qian, Pin
Yang, Minghui
Qu, Fengli
TI Fluorescent turn-on determination of the activity of peptidases using
peptide templated gold nanoclusters
SO MICROCHIMICA ACTA
LA English
DT Article
DE beta-Secretases; APP cleaving enzyme; BACE1; beta-amyloid precursor
protein; Transmission electron microscopy; Fluorometry
ID AMYLOID PRECURSOR PROTEIN; HUMAN BETA-SECRETASE; BIOLOGICAL
APPLICATIONS; SILVER NANOCLUSTERS; INHIBITORS; NANOPARTICLES; DISEASE;
ENZYMES; SITE; CELL
AB The fluorescence intensity of gold nanoclusters (AuNCs) is inversely related to the length of a peptide immobilized on its surface. This finding has been exploited to design a turn-on fluorescent method for the determination of the activity of peptidase. The beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) was chosen as a model peptidase. BACE1 cleaves the peptide substrates on AuNCs, and the fluorescence intensity of the AuNCs (at exCitation/emission wavelengths of 320/405 nm) carrying the rest of the cleaved peptide is significantly higher than that of the AuNCs with uncleaved peptide. Transmission electron microscopy revealed a decrease in the size of the AuNCs which is assumed cause fluorescence enhancement. The assay was applied to the determination of BACE1 activity in spiked cell lysates, and recoveries were between 96.9 and 104.0 %.
C1 [Luo, Junjun; Wang, Liqiang; Zeng, Ke; Shen, Congcong; Qian, Pin; Yang, Minghui] Cent S Univ, Coll Chem & Chem Engn, Changsha 410083, Hunan, Peoples R China.
[Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA.
[Qu, Fengli] Qufu Normal Univ, Coll Chem & Chem Engn, Qufu 273165, Shandong, Peoples R China.
RP Yang, MH (reprint author), Cent S Univ, Coll Chem & Chem Engn, Changsha 410083, Hunan, Peoples R China.; Qu, FL (reprint author), Qufu Normal Univ, Coll Chem & Chem Engn, Qufu 273165, Shandong, Peoples R China.
EM yangminghui@csu.edu.cn; fengliquhn@hotmail.com
FU National Natural Science Foundation of China [21575165, 21375076];
Natural Science Foundation of Hunan province [2015JJ1019]
FX The authors appreciate the support of this work by the National Natural
Science Foundation of China (No. 21575165, 21375076) and Natural Science
Foundation of Hunan province (No. 2015JJ1019).
NR 31
TC 6
Z9 6
U1 12
U2 31
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0026-3672
EI 1436-5073
J9 MICROCHIM ACTA
JI Microchim. Acta
PD FEB
PY 2016
VL 183
IS 2
BP 605
EP 610
DI 10.1007/s00604-015-1683-5
PG 6
WC Chemistry, Analytical
SC Chemistry
GA DD8KX
UT WOS:000370176500011
ER
PT J
AU Wake, LM
Ahn, I
Farooqui, M
Hahn, J
Tian, X
Steller-Stevenson, M
Marti, G
Wiestner, A
Maric, I
AF Wake, Laura M.
Ahn, Inhye
Farooqui, Mohammed
Hahn, Jamie
Tian, Xin
Steller-Stevenson, Maryalice
Marti, Gerald
Wiestner, Adrian
Maric, Irina
TI Dual Antibody Immunohistochemistry: A Cost-Efficient and Sensitive New
Tool for the Detection of Minimal Residual CLL
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 12-18, 2016
CL Seattle, WA
SP US & Canadian Acad Pathol
C1 NCI, NIH, Bethesda, MD 20892 USA.
NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
NIH, CC, DLM, Bldg 10, Bethesda, MD 20892 USA.
US FDA, CDRH, Bethesda, MD 20014 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2016
VL 29
SU 2
MA 1507
BP 382A
EP 382A
PG 1
WC Pathology
SC Pathology
GA DE0GI
UT WOS:000370302502513
ER
PT J
AU Gamalo, MA
Wu, R
Tiwari, RC
AF Gamalo, M. Amper
Wu, Rui
Tiwari, Ram C.
TI Bayesian approach to non-inferiority trials for normal means
SO STATISTICAL METHODS IN MEDICAL RESEARCH
LA English
DT Article
DE Non-inferiority; prior distribution; Jeffrey's prior; posterior
distribution; fixed-margin approach
ID ACTIVE-CONTROL TRIALS; STATISTICAL-METHODS; MEDICAL STATISTICS;
CLINICAL-TRIALS; PLACEBO; ISSUES; CHOICE; DESIGN; DELTA
AB Regulatory framework recommends that novel statistical methodology for analyzing trial results parallels the frequentist strategy, e.g. the new method must protect type-I error and arrive at a similar conclusion. Keeping these in mind, we construct a Bayesian approach for non-inferiority trials with normal response. A non-informative prior is assumed for the mean response of the experimental treatment and Jeffrey's prior for its corresponding variance when it is unknown. The posteriors of the mean response and variance of the treatment in historical trials are then assumed as priors for its corresponding parameters in the current trial, where that treatment serves as the active control. From these priors, a Bayesian decision criterion is derived to determine whether the experimental treatment is non-inferior to the active control. This criterion is evaluated and compared with the frequentist method using simulation studies. Results show that both Bayesian and frequentist approaches perform alike, but the Bayesian approach has a higher power when the variances are unknown. Both methods also arrive at the same conclusion of non-inferiority when applied on two real datasets. A major advantage of the proposed Bayesian approach lies in its ability to provide posterior probabilities for varying effect sizes of the experimental treatment over the active control.
C1 [Gamalo, M. Amper] US FDA, Off Biostat, Rockville, MD 20993 USA.
[Wu, Rui] Univ Connecticut, Dept Stat, Storrs, CT USA.
[Tiwari, Ram C.] US FDA, Off Biostat, Stat Sci & Policy, Rockville, MD 20857 USA.
RP Gamalo, MA (reprint author), US FDA, Off Biostat, Rockville, MD 20993 USA.
EM Mark.Gamalo@fda.hhs.gov
NR 28
TC 2
Z9 2
U1 0
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0962-2802
EI 1477-0334
J9 STAT METHODS MED RES
JI Stat. Methods Med. Res.
PD FEB
PY 2016
VL 25
IS 1
BP 221
EP 240
DI 10.1177/0962280212448723
PG 20
WC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Statistics & Probability
SC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Mathematics
GA DE5PZ
UT WOS:000370685000013
PM 22619277
ER
PT J
AU Zhang, ZW
Zhou, J
Cao, WH
Zhang, J
AF Zhang, Zhiwei
Zhou, Jie
Cao, Weihua
Zhang, Jun
TI Causal inference with a quantitative exposure
SO STATISTICAL METHODS IN MEDICAL RESEARCH
LA English
DT Article
DE Dose-response relationship; double robustness; inverse probability
weighting; outcome regression; propensity function; propensity score;
stratification
ID DOUBLY ROBUST ESTIMATION; PROPENSITY SCORE; PHYSICAL-ACTIVITY;
BODY-COMPOSITION; INCOMPLETE DATA; MISSING DATA; MODELS; BIAS
AB The current statistical literature on causal inference is mostly concerned with binary or categorical exposures, even though exposures of a quantitative nature are frequently encountered in epidemiologic research. In this article, we review the available methods for estimating the dose-response curve for a quantitative exposure, which include ordinary regression based on an outcome regression model, inverse propensity weighting and stratification based on a propensity function model, and an augmented inverse propensity weighting method that is doubly robust with respect to the two models. We note that an outcome regression model often imposes an implicit constraint on the dose-response curve, and propose a flexible modeling strategy that avoids constraining the dose-response curve. We also propose two new methods: a weighted regression method that combines ordinary regression with inverse propensity weighting and a stratified regression method that combines ordinary regression with stratification. The proposed methods are similar to the augmented inverse propensity weighting method in the sense of double robustness, but easier to implement and more generally applicable. The methods are illustrated with an obstetric example and compared in simulation studies.
C1 [Zhang, Zhiwei; Zhou, Jie; Cao, Weihua] US FDA, Div Biostat, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, MOE, Shanghai 200030, Peoples R China.
[Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Shanghai Key Lab Childrens Environm Hlth, Shanghai 200030, Peoples R China.
RP Zhang, ZW (reprint author), US FDA, Div Biostat, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
EM zhiwei_zhang@yahoo.com
FU Intramural Research Program of the National Institutes of Health; Eunice
Kennedy Shriver National Institute of Child Health and Human Development
FX Zhiwei Zhang and Jun Zhang were supported in part by the Intramural
Research Program of the National Institutes of Health, Eunice Kennedy
Shriver National Institute of Child Health and Human Development.
NR 41
TC 2
Z9 2
U1 4
U2 5
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0962-2802
EI 1477-0334
J9 STAT METHODS MED RES
JI Stat. Methods Med. Res.
PD FEB
PY 2016
VL 25
IS 1
BP 314
EP 335
DI 10.1177/0962280212452333
PG 21
WC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Statistics & Probability
SC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Mathematics
GA DE5PZ
UT WOS:000370685000018
PM 22729475
ER
PT J
AU Muthukumarana, S
Tiwari, RC
AF Muthukumarana, Saman
Tiwari, Ram C.
TI Meta-analysis using Dirichlet process
SO STATISTICAL METHODS IN MEDICAL RESEARCH
LA English
DT Article
DE Clustering; heterogeneity; log pseudo-marginal likelihood; Markov chain
Monte Carlo; odds ratio
ID DISTRIBUTIONS; TRIALS; MODELS; HETEROGENEITY; PRIORS
AB This article develops a Bayesian approach for meta-analysis using the Dirichlet process. The key aspect of the Dirichlet process in meta-analysis is the ability to assess evidence of statistical heterogeneity or variation in the underlying effects across study while relaxing the distributional assumptions. We assume that the study effects are generated from a Dirichlet process. Under a Dirichlet process model, the study effects parameters have support on a discrete space and enable borrowing of information across studies while facilitating clustering among studies. We illustrate the proposed method by applying it to a dataset on the Program for International Student Assessment on 30 countries. Results from the data analysis, simulation studies, and the log pseudo-marginal likelihood model selection procedure indicate that the Dirichlet process model performs better than conventional alternative methods.
C1 [Muthukumarana, Saman] Univ Manitoba, Dept Stat, Winnipeg, MB R3T 2N2, Canada.
[Tiwari, Ram C.] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Muthukumarana, S (reprint author), Univ Manitoba, Dept Stat, Winnipeg, MB R3T 2N2, Canada.
EM Saman.Muthukumarana@ad.umanitoba.ca
FU Natural Sciences and Engineering Research Council of Canada
FX Dr Muthukumarana's research has been partially supported by grant from
the Natural Sciences and Engineering Research Council of Canada.
NR 35
TC 0
Z9 0
U1 2
U2 8
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0962-2802
EI 1477-0334
J9 STAT METHODS MED RES
JI Stat. Methods Med. Res.
PD FEB
PY 2016
VL 25
IS 1
BP 352
EP 365
DI 10.1177/0962280212453891
PG 14
WC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Statistics & Probability
SC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Mathematics
GA DE5PZ
UT WOS:000370685000020
PM 22802045
ER
PT J
AU Proschan, MA
Dodd, LE
Price, D
AF Proschan, Michael A.
Dodd, Lori E.
Price, Dionne
TI Statistical considerations for a trial of Ebola virus disease
therapeutics
SO CLINICAL TRIALS
LA English
DT Article
DE Barnard's test; Bayesian methods; beta-binomial distribution;
conditional power; emerging infectious diseases; Fisher's exact test;
group-sequential monitoring; non-informative prior
ID CLINICAL-TRIALS; VACCINE TRIALS; TESTS
AB The 2014 West African outbreak of Ebola virus ravaged Liberia, Sierra Leone, and Guinea, causing hemorrhagic fever and death. The need to identify effective therapeutics was acute. The usual drug development paradigm of phase I, followed by phase II, and then phase III trials would take too long. These and other factors led to the design of a clinical trial of Ebola virus disease therapeutics that differs from more conventional clinical trial designs. This article describes the Ebola virus disease medical countermeasures trial design and the thinking behind it.
C1 [Proschan, Michael A.; Dodd, Lori E.] NIAID, 5601 Fishers Lane,Room 4C30,MSC 9820, Bethesda, MD 20892 USA.
[Price, Dionne] US FDA, Silver Spring, MD USA.
RP Proschan, MA (reprint author), NIAID, 5601 Fishers Lane,Room 4C30,MSC 9820, Bethesda, MD 20892 USA.
EM ProschaM@niaid.nih.gov
FU Intramural NIH HHS [Z99 AI999999]
NR 13
TC 6
Z9 6
U1 0
U2 9
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1740-7745
EI 1740-7753
J9 CLIN TRIALS
JI Clin. Trials
PD FEB
PY 2016
VL 13
IS 1
BP 39
EP 48
DI 10.1177/1740774515620145
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DD5UT
UT WOS:000369990700007
PM 26768567
ER
PT J
AU Russek-Cohen, E
Rubin, D
Price, D
Sun, W
Cox, E
Borio, L
AF Russek-Cohen, Estelle
Rubin, Daniel
Price, Dionne
Sun, Wellington
Cox, Edward
Borio, Luciana
TI A US Food and Drug Administration perspective on evaluating medical
products for Ebola
SO CLINICAL TRIALS
LA English
DT Article
DE Therapeutic clinical trials; vaccine clinical trials; Ebola
ID SIERRA-LEONE; VACCINE; TRIALS
C1 [Russek-Cohen, Estelle; Sun, Wellington] US FDA, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
[Rubin, Daniel; Price, Dionne; Cox, Edward] US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
[Borio, Luciana] US FDA, Off Commissioner, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
RP Russek-Cohen, E (reprint author), US FDA, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM estelle.russek-cohen@fda.hhs.gov
NR 13
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U1 0
U2 3
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1740-7745
EI 1740-7753
J9 CLIN TRIALS
JI Clin. Trials
PD FEB
PY 2016
VL 13
IS 1
BP 105
EP 109
DI 10.1177/1740774515620613
PG 5
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DD5UT
UT WOS:000369990700018
PM 26768565
ER
PT J
AU Sanad, YM
Johnson, K
Park, SH
Han, J
Deck, J
Foley, SL
Kenney, B
Ricke, S
Nayak, R
AF Sanad, Yasser M.
Johnson, Kelly
Park, Si Hong
Han, Jing
Deck, Joanna
Foley, Steven L.
Kenney, Brett
Ricke, Steven
Nayak, Rajesh
TI Molecular Characterization of Salmonella enterica Serovars Isolated from
a Turkey Production Facility in the Absence of Selective Antimicrobial
Pressure
SO FOODBORNE PATHOGENS AND DISEASE
LA English
DT Article
ID ANTIBIOTIC-RESISTANT SALMONELLA; ESCHERICHIA-COLI; UNITED-STATES;
POULTRY FARMS; PREVALENCE; VIRULENCE; CHICKEN; SEROTYPES; PROFILES;
PLASMID
AB This study evaluated antimicrobial resistance and virulence factors in Salmonella enterica isolated from a turkey flock in which the birds were raised in an environment where antimicrobials were not administered to the birds, either through feed or water. Salmonella was isolated from turkeys and various environmental samples in the facility using conventional microbiological procedures. Isolates were serotyped and analyzed phenotypically by antimicrobial resistance profiling and genotypically by pulsed-field gel electrophoresis (PFGE) fingerprinting, integron analysis, plasmid profiling, replicon-based incompatibility (Inc) group typing, and virulence gene profiling. Ninety-five S. enterica isolates were isolated from cecal contents (n=29), feed (n=22), leftover feed (n=13), litter (n=12), drinkers (n=10), environment (n=8), and an insect. The following serotypes were identified: Montevideo (24%), Anatum (22%), Agona (17%), Kentucky and Worthington (12%), Senftenberg (11%), and rough phenotypes (3%). The majority of isolates (61/95; 64%) were susceptible to 12 antimicrobials tested; however, despite the absence of antimicrobials in the facility, approximately 36% of the isolates were resistant to two to five antimicrobials. Class 1 integrons were detected in 8% of the isolates. The integron sequence analysis revealed dihydrofolate reductase (dhfr) and aminoglycoside adenylyl transferase (aadA2) genes, which encode trimethoprim and streptomycin resistance, respectively. Furthermore, 71% of the isolates had at least one plasmid. There were five plasmid replicon types identified among the isolates, including IncI1, IncHI2, IncFIIA, IncB/O, and IncP, with variable prevalence among the serotypes. All 95 isolates tested polymerase chain reaction-positive for 19 virulence genes and negative for virD4 and virB4. The virulence gene profiles were similar within the isolates from the same serotype. Within particular serotypes, PFGE patterns revealed 100% similarity, even when the bacterial strains were isolated from different sources, indicating cross-colonization of sources within the turkey facility. On this antibiotic-free turkey farm, turkeys and feed appeared to be the major reservoirs of multidrug-resistant Salmonella, which harbored multiple virulence genes.
C1 [Sanad, Yasser M.; Johnson, Kelly; Han, Jing; Deck, Joanna; Foley, Steven L.; Nayak, Rajesh] US FDA, Div Microbiol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
[Park, Si Hong; Ricke, Steven] Univ Arkansas, Ctr Food Safety, Fayetteville, AR 72701 USA.
[Park, Si Hong; Ricke, Steven] Univ Arkansas, Dept Food Sci, Fayetteville, AR 72703 USA.
[Kenney, Brett] W Virginia Univ, Dept Anim & Nutr Sci, Morgantown, WV 26506 USA.
RP Nayak, R (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM Rajesh.Nayak@fda.hhs.gov
FU Oak Ridge Institute for Science and Education
FX We thank Dr. Alessandra Carattoli for providing the positive controls
for Incompatibility replicon typing and Dr. Bashar Shaheen for his
technical expertise. We also thank Drs. Carl Cerniglia, Sangeeta Khare,
and John Sutherland for reviewing the manuscript. Authors Yasser M.
Sanad, Kelly Johnson, and Jing Han were supported through the Oak Ridge
Institute for Science and Education. The views presented in this article
do not necessarily reflect those of the U.S. Food and Drug
Administration.
NR 43
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U1 6
U2 11
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1535-3141
EI 1556-7125
J9 FOODBORNE PATHOG DIS
JI Foodborne Pathog. Dis.
PD FEB 1
PY 2016
VL 13
IS 2
BP 80
EP 87
DI 10.1089/fpd.2015.2002
PG 8
WC Food Science & Technology
SC Food Science & Technology
GA DD2OJ
UT WOS:000369761700005
PM 26653998
ER
PT J
AU Nyan, DC
Swinson, KL
AF Nyan, Dougbeh-Chris
Swinson, Kevin L.
TI A method for rapid detection and genotype identification of hepatitis C
virus 1-6 by one-step reverse transcription loop-mediated isothermal
amplification
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE Hepatitis C virus; Detection; Isothermal amplification; Genotype
identification; Plasma; Serum
ID HEPATOCELLULAR-CARCINOMA; INFECTION; REGION; RNA; QUANTIFICATION;
CIRRHOSIS; ASSAY
AB Objective: Hepatitis C virus (HCV) is probably the leading cause of liver cirrhosis and hepatocellular carcinoma globally. Diagnostic tools conventionally used for the detection and identification of HCV infection are technically demanding, time-consuming, and costly for resource-limited environments. This study reports the development of the first rapid loop-mediated reverse transcription isothermal amplification assay that rapidly detects and identifies HCV genotypes in blood components.
Methods: RNA extracted from donor plasma and serum specimens was applied to a one-step reverse transcription loop-mediated isothermal amplification reaction performed with HCV-specific oligonucleotides. Reactions were conducted at 63.5 degrees C for 30-60 min. The diagnostic characteristics of the assay were investigated and validated with clinical specimens.
Results: Electrophoretic analysis of amplification revealed detection and identification of HCV genotypes 1-6. Positive amplification revealed unique ladder-like banding patterns that identified each HCV genotype. The assay demonstrated a sensitivity of 91.5% and specificity of 100%. Rapid naked-eye detection of HCV infection was facilitated by observation of an intense fluorescent glow of amplified targets under UV illumination.
Conclusion: These diagnostic characteristics highlight the potential utility of this assay for the rapid detection and genotype identification of HCV infection in field and point-of-care settings in endemic regions and resource-limited environments. (C) 2015 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
C1 [Nyan, Dougbeh-Chris] US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
[Swinson, Kevin L.] Morgan State Univ, Dept Biol, Baltimore, MD 21239 USA.
RP Nyan, DC (reprint author), US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM dnyan@doctor.com
NR 38
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U1 3
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1201-9712
EI 1878-3511
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD FEB
PY 2016
VL 43
BP 30
EP 36
DI 10.1016/j.ijid.2015.12.002
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA DD2ZE
UT WOS:000369789900007
PM 26686938
ER
PT J
AU Reddy, NR
Patazca, E
Morrissey, TR
Skinner, GE
Loeza, V
Schill, KM
Larkin, JW
AF Reddy, N. Rukma
Patazca, Eduardo
Morrissey, Travis R.
Skinner, Guy E.
Loeza, Viviana
Schill, Kristin M.
Larkin, John W.
TI Thermal and Pressure-Assisted Thermal Destruction Kinetics for Spores of
Type A Clostridium botulinum and Clostridium sporogenes PA3679
SO JOURNAL OF FOOD PROTECTION
LA English
DT Article
DE Clostridium botulinum; Clostridium sporogenes PA3679; High pressure
processing; Resistance; Spores
ID ELEVATED-TEMPERATURES; B SPORES; PA 3679; INACTIVATION; RESISTANCE;
SPORULATION; ENDOSPORES; STRAIN; HEAT
AB The purpose of this study was to determine the inactivation kinetics of the spores of the most resistant proteolytic Clostridium botulinum strains (Giorgio-A and 69-A, as determined from an earlier screening study) and of Clostridium sporogenes PA3679 and to compare the thermal and pressure-assisted thermal resistance of these spores. Spores of these strains were prepared using a biphasic medium method. C. sporogenes PA3679 spores were heat treated before spore preparation. Using laboratory-scale and pilot-scale pressure test systems, spores of Giorgio-A, 69-A, and PA3679 suspended in ACES [N-(2-acetamido)-2-aminoethanesulfonic acid] buffer (pH 7.0) were exposed to various combinations of temperature (93 to 121 degrees C) and pressure (0.1 to 750 MPa) to determine their resistance. More than a 5-log reduction occurred after 3 min at 113 degrees C for spores of Giorgio-A and 69-A and after 5 min at 117 degrees C for spores of PA3679. A combination of high temperatures (93 to 121 degrees C) and pressures yielded greater log reductions of spores of Giorgio-A, 69-A, and PA3679 compared with reduction obtained with high temperatures alone. No survivors from initial levels (>5.0 log CFU) of Giorgio-A and 69-A were detected when processed at a combination of high temperature (117 and 121 degrees C) and high pressure (600 and 750 MPa) for <1 min in a pilot-scale pressure test system. Increasing pressure from 600 to 750 MPa at 117 C decreased the time from 2.7 to 1 min for a >4.5-log reduction of PA3679 spores. Thermal D-values of Giorgio-A, 69-A, and PA3679 spores decreased (i.e., 29.1 to 0.33 min for Giorgio-A, 40.5 to 0.27 min for 69-A, and 335.2 to 2.16 min for PA3679) as the temperature increased from 97 to 117 degrees C. Pressure-assisted thermal D-values of Giorgio-A, 69-A, and PA3679 also decreased as temperature increased from 97 to 121 degrees C at both pressures (600 and 750 MPa) (i.e., 17.19 to 0.15 min for Giorgio-A, 9.58 to 0.15 min for 69-A, and 12.93 to 0.33 min for PA3679 at 600 MPa). At higher temperatures (117 or 121 degrees C), increasing pressure from 600 to 750 MPa had an effect on pressure-assisted thermal D-values of PA3679 (i.e., at 117 degrees C, pressure-assisted thermal D-value decreased from 0.55 to 0.28 min as pressure increased from 600 to 750 MPa), but pressure had no effect on pressure-assisted thermal D-values of Giorgio-A and 69-A. When compared with Giorgio-A and 69-A, PA3679 had higher thermal and pressure-assisted thermal D-values. C. sporogenes PA3679 spores were generally more resistant to combinations of high pressure and high temperature than were the spores of the C. botulinum strains tested in this study.
C1 [Reddy, N. Rukma; Morrissey, Travis R.; Skinner, Guy E.; Schill, Kristin M.; Larkin, John W.] US FDA, Ctr Food Safety & Appl Nutr, Div Food Proc Sci & Technol, 6502 South Archer Rd, Bedford Pk, IL 60501 USA.
[Patazca, Eduardo; Loeza, Viviana] IIT, Inst Food Safety & Hlth, 6502 South Archer Rd, Bedford, IL 60501 USA.
RP Reddy, NR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Food Proc Sci & Technol, 6502 South Archer Rd, Bedford Pk, IL 60501 USA.
EM rukma.reddy@fda.hhs.gov
FU U.S. Food and Drug Administration; Illinois Institute of Technology
FX We acknowledge the assistance of Lindsay Halik for performing some
experiments and Hossein Daryaei for providing pressure-assisted thermal
D-value data of C. sporogenes PA3679 for temperatures 113 to 121 degrees
C. This work was supported by a grant from the U.S. Food and Drug
Administration to the Institute for Food Safety and Health, Illinois
Institute of Technology.
NR 32
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U1 6
U2 14
PU INT ASSOC FOOD PROTECTION
PI DES MOINES
PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA
SN 0362-028X
EI 1944-9097
J9 J FOOD PROTECT
JI J. Food Prot.
PD FEB
PY 2016
VL 79
IS 2
BP 253
EP 262
DI 10.4315/0362-028X.JFP-15-310
PG 10
WC Biotechnology & Applied Microbiology; Food Science & Technology
SC Biotechnology & Applied Microbiology; Food Science & Technology
GA DD2TR
UT WOS:000369775600009
PM 26818986
ER
PT J
AU Aikin, KJ
Sullivan, HW
Betts, KR
AF Aikin, Kathryn J.
Sullivan, Helen W.
Betts, Kevin R.
TI Disease Information in Direct-to-Consumer Prescription Drug Print Ads
SO JOURNAL OF HEALTH COMMUNICATION
LA English
DT Article
ID ADVERTISEMENTS
AB Direct-to-consumer (DTC) prescription drug advertisements sometimes include information about the disease condition in addition to information about the advertised product. Although the intent of such information is to educate about the disease condition, in some cases consumers may mistakenly assume that the drug will address all of the potential consequences of the condition mentioned in the ad. We investigated the effects of adding disease information to DTC prescription drug print ads on consumer product perceptions and understanding. Participants (4,064 adults) viewed 1 of 15 DTC print ads for fictitious prescription drugs indicated to treat chronic obstructive pulmonary disease, anemia, or lymphoma that varied in disease information presence, type, and format. Participants answered questions that assessed risk and benefit memory, perception, and behavioral intention. Results indicate that exposure to disease information as part of DTC prescription drug ads can promote the impression that the drug addresses consequences of the condition that are not part of the drug's indication.
C1 [Aikin, Kathryn J.; Sullivan, Helen W.; Betts, Kevin R.] US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
RP Aikin, KJ (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM Kathryn.Aikin@fda.hhs.gov
NR 25
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U1 0
U2 2
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1081-0730
EI 1087-0415
J9 J HEALTH COMMUN
JI J. Health Commun.
PD FEB 1
PY 2016
VL 21
IS 2
BP 228
EP 239
DI 10.1080/10810730.2015.1058440
PG 12
WC Communication; Information Science & Library Science
SC Communication; Information Science & Library Science
GA DD3TX
UT WOS:000369847000010
PM 26717304
ER
PT J
AU Madak-Erdogan, Z
Gong, P
Zhao, YRC
Xu, LW
Wrobel, KU
Hartman, JA
Wang, M
Cam, A
Iwaniec, UT
Turner, RT
Twaddle, NC
Doerge, DR
Khan, IA
Katzenellenbogen, JA
Katzenellenbogen, BS
Helferich, WG
AF Madak-Erdogan, Zeynep
Gong, Ping
Zhao, Yiru Chen
Xu, Liwen
Wrobel, Kinga U.
Hartman, James A.
Wang, Michelle
Cam, Anthony
Iwaniec, Urszula T.
Turner, Russell T.
Twaddle, Nathan C.
Doerge, Daniel R.
Khan, Ikhlas A.
Katzenellenbogen, John A.
Katzenellenbogen, Benita S.
Helferich, William G.
TI Dietary licorice root supplementation reduces diet-induced weight gain,
lipid deposition, and hepatic steatosis in ovariectomized mice without
stimulating reproductive tissues and mammary gland
SO MOLECULAR NUTRITION & FOOD RESEARCH
LA English
DT Article
DE Botanical estrogens; Dietary supplements; Estrogen receptor; Licorice
root; Menopause; Metabolism
ID FATTY LIVER-DISEASE; HORMONE-THERAPY; POSTMENOPAUSAL WOMEN;
INSULIN-RESISTANCE; METABOLIC SYNDROME; GLUCOSE-TOLERANCE;
ADIPOSE-TISSUE; BREAST-CANCER; X RECEPTORS; MECHANISMS
AB ScopeWe studied the impact of dietary supplementation with licorice root components on diet-induced obesity, fat accumulation, and hepatic steatosis in ovariectomized C57BL/6 mice as a menopause model.
Materials and methodsWe evaluated the molecular and physiological effects of dietary licorice root administered to ovariectomized C57BL/6 mice as root powder (LRP), extracts (LRE), or isolated isoliquiritigenin (ILQ) on reproductive (uterus and mammary gland) and nonreproductive tissues important in regulating metabolism (liver, perigonadal, perirenal, mesenteric, and subcutaneous fat). Quantitative outcome measures including body weight, fat distribution (magnetic resonance imaging), food consumption, bone density and weight (Dual-energy X-ray absorptiometry), and gene expression were assessed by the degree of restoration to the preovariectomized health state. We characterized histological (H&E and oil red O staining) and molecular properties (expression of certain disease markers) of these tissues, and correlated these with metabolic phenotype as well as blood levels of bioactives.
ConclusionAlthough LRE and ILQ provided some benefit, LRP was the most effective in reducing body weight gain, overall fat deposition, liver steatosis, and expression of hepatic lipid synthesis genes following ovariectomy. Our data demonstrate that licorice root provided improvement of multiple metabolic parameters under conditions of low estrogen and high-fat diets without stimulating reproductive tissues.
C1 [Madak-Erdogan, Zeynep; Wrobel, Kinga U.; Hartman, James A.; Wang, Michelle; Cam, Anthony; Helferich, William G.] Univ Illinois, Bot Res Ctr, Dept Food Sci, Urbana, IL USA.
[Madak-Erdogan, Zeynep; Wrobel, Kinga U.; Hartman, James A.; Wang, Michelle; Cam, Anthony; Helferich, William G.] Univ Illinois, Dept Human Nutr, Urbana, IL USA.
[Gong, Ping; Zhao, Yiru Chen; Xu, Liwen; Katzenellenbogen, Benita S.] Univ Illinois, Mol & Integrat Physiol, Urbana, IL USA.
[Katzenellenbogen, John A.] Univ Illinois, Chem, Urbana, IL USA.
[Iwaniec, Urszula T.; Turner, Russell T.] Oregon State Univ, Skeletal Biol Lab, Sch Biol & Populat Hlth Sci, Corvallis, OR 97331 USA.
[Twaddle, Nathan C.; Doerge, Daniel R.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Khan, Ikhlas A.] Univ Mississippi, Natl Ctr Nat Prod Res, Sch Pharm, University, MS 38677 USA.
[Khan, Ikhlas A.] Univ Mississippi, Div Pharmacognosy, Dept BioMol Sci, Sch Pharm, University, MS 38677 USA.
RP Madak-Erdogan, Z (reprint author), Univ Illinois, Bot Res Ctr, Dept Food Sci, Urbana, IL USA.
EM zmadake2@illinois.edu
OI Madak-Erdogan, Zeynep/0000-0003-2607-1643
FU NIH from the National Center for Complementary and Alternative Medicines
(NCCAM) [P50AT006268]; Office of Dietary Supplements (ODS); National
Cancer Institute (NCI); National Institute of Food and Agriculture, U.S.
Department of Agriculture [ILLU-698-909]
FX This work was supported by the NIH [P50AT006268] (W. G. H., B. S. K., J.
A. K., D. R. D., I. A. K.) from the National Center for Complementary
and Alternative Medicines (NCCAM), the Office of Dietary Supplements
(ODS), and the National Cancer Institute (NCI) and National Institute of
Food and Agriculture, U.S. Department of Agriculture, award ILLU-698-909
(Z. M. E.). Its contents are solely the responsibility of the authors
and do not necessarily represent the official views of the NIH, U.S.
Food and Drug Administration, and U.S. Department of Agriculture.
NR 50
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U1 2
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1613-4125
EI 1613-4133
J9 MOL NUTR FOOD RES
JI Mol. Nutr. Food Res.
PD FEB
PY 2016
VL 60
IS 2
BP 369
EP 380
DI 10.1002/mnfr.201500445
PG 12
WC Food Science & Technology
SC Food Science & Technology
GA DD5KO
UT WOS:000369962800012
PM 26555669
ER
PT J
AU Heidor, R
de Conti, A
Ortega, JF
Furtado, KS
Silva, RC
Tavares, PELM
Purgatto, E
Ract, JNR
de Paiva, SAR
Gioielli, LA
Pogribny, IP
Moreno, FS
AF Heidor, Renato
de Conti, Aline
Ortega, Juliana F.
Furtado, Kelly S.
Silva, Roberta C.
Tavares, Paulo E. L. M.
Purgatto, Eduardo
Ract, Juliana N. R.
de Paiva, Sergio A. R.
Gioielli, Luiz A.
Pogribny, Igor P.
Moreno, Fernando S.
TI The chemopreventive activity of butyrate-containing structured lipids in
experimental rat hepatocarcinogenesis
SO MOLECULAR NUTRITION & FOOD RESEARCH
LA English
DT Article
DE Chemoprevention; Liver carcinogenesis; Rat; Structured lipids;
Tributyrin
ID HEPATOCELLULAR-CARCINOMA; SIGNALING PATHWAY; SODIUM-BUTYRATE; DNA
METHYLATION; ACID PRODRUG; FLAXSEED OIL; CYCLIN D1; CANCER; TRIBUTYRIN;
CHROMATIN
AB ScopeEmerging evidence indicates that the use of bioactive food components is a promising strategy to prevent the development of liver cancer. The goal of this study was to examine the chemopreventive effect of butyrate-containing structured lipids (STLs) produced by an enzymatic interesterification of tributyrin and flaxseed oil on rat hepatocarcinogenesis.
Methods and resultsMale Wistar rats were subjected to a classic resistant hepatocyte model of liver carcinogenesis and treated with STLs, tributyrin or flaxseed oil during the initial phases of hepatocarcinogenesis. Treatment with STLs and tributyrin strongly inhibited the development of preneoplastic liver lesions. The chemopreventive activity of tributyrin was associated with the induction of apoptosis and reduction of the expression of major activated hepatocarcinogenesis-related oncogenes. Treatment with STLs caused substantially greater inhibitory effects than tributyrin on oncogene expression.
ConclusionThese results demonstrate that the tumor-suppressing activity of butyrate-containing STLs is associated with its ability to prevent and inhibit activation of major hepatocarcinogenesis-related oncogenes. Enrichment of histone H3K9me3 and H3K27me3 at the promoter of Myc and Ccnd1 genes may be related to the inhibitory effect on oncogene expression in the livers of STL-treated rats.
C1 [Heidor, Renato; Ortega, Juliana F.; Furtado, Kelly S.; Tavares, Paulo E. L. M.; Moreno, Fernando S.] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Food & Expt Nutr, Lab Diet Nutr & Canc, Sao Paulo, Brazil.
[de Conti, Aline; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
[Silva, Roberta C.; Ract, Juliana N. R.; Gioielli, Luiz A.] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Biochem & Pharmaceut Technol, Sao Paulo, Brazil.
[Purgatto, Eduardo] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Food & Expt Nutr, Lab Food Chem & Biochem, BR-05508 Sao Paulo, Brazil.
[de Paiva, Sergio A. R.] Sao Paulo State Univ, Botucatu Med Sch, Dept Internal Med, Botucatu, SP, Brazil.
[Heidor, Renato; Furtado, Kelly S.; Purgatto, Eduardo; Moreno, Fernando S.] Univ Sao Paulo, Fac Pharmaceut Sci, Adv Res Ctr Food Sci & Nutr NAPAN, BR-05508 Sao Paulo, Brazil.
[Heidor, Renato; Purgatto, Eduardo; de Paiva, Sergio A. R.; Moreno, Fernando S.] Univ Sao Paulo, Fac Pharmaceut Sci, Food Res Ctr FORC, BR-05508 Sao Paulo, Brazil.
RP Moreno, FS (reprint author), Univ Sao Paulo, Fac Pharmaceut Sci, Dept Food & Expt Nutr, Lab Diet Nutr & Canc, Sao Paulo, Brazil.; Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.; Moreno, FS (reprint author), Univ Sao Paulo, Fac Pharmaceut Sci, Adv Res Ctr Food Sci & Nutr NAPAN, BR-05508 Sao Paulo, Brazil.; Moreno, FS (reprint author), Univ Sao Paulo, Fac Pharmaceut Sci, Food Res Ctr FORC, BR-05508 Sao Paulo, Brazil.
EM igor.pogribny@fda.hhs.gov; rmoreno@usp.br
RI Purgatto, Eduardo/C-7707-2009; Food Research Center, FoRC/J-7793-2015;
Heidor, Renato/O-1125-2013; Ract, Juliana/D-2367-2011; Moreno,
Fernando/I-1943-2013; Paiva, Sergio/A-5101-2008
OI Purgatto, Eduardo/0000-0002-7372-1197; Food Research Center,
FoRC/0000-0003-0248-8911; Heidor, Renato/0000-0001-7427-6518; Ract,
Juliana/0000-0001-5845-9445; Paiva, Sergio/0000-0003-4412-1990
NR 50
TC 1
Z9 1
U1 2
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1613-4125
EI 1613-4133
J9 MOL NUTR FOOD RES
JI Mol. Nutr. Food Res.
PD FEB
PY 2016
VL 60
IS 2
BP 420
EP 429
DI 10.1002/mnfr.201500643
PG 10
WC Food Science & Technology
SC Food Science & Technology
GA DD5KO
UT WOS:000369962800017
PM 26548572
ER
PT J
AU Ghasriani, H
Hodgson, DJ
Brinson, RG
McEwen, I
Buhse, LF
Kozlowski, S
Marino, JP
Aubin, Y
Keire, DA
AF Ghasriani, Houman
Hodgson, Derek J.
Brinson, Robert G.
McEwen, Ian
Buhse, Lucinda F.
Kozlowski, Steven
Marino, John P.
Aubin, Yves
Keire, David A.
TI Precision and robustness of 2D-NMR for structure assessment of
filgrastim biosimilars
SO NATURE BIOTECHNOLOGY
LA English
DT Letter
ID ORDER STRUCTURE; NMR
C1 [Ghasriani, Houman; Buhse, Lucinda F.; Keire, David A.] US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO USA.
[Hodgson, Derek J.; Aubin, Yves] Hlth Canada, Biol & Genet Therapies Directorate, Ctr Biol Evaluat, Ottawa, ON K1A 0L2, Canada.
[Brinson, Robert G.; Marino, John P.] NIST, Inst Biosci & Biotechnol Res, Rockville, MD USA.
[McEwen, Ian] Med Prod Agcy Sweden, Uppsala, Sweden.
[Kozlowski, Steven] US FDA, Ctr Drug Evaluat & Res, Off Biotechnol Prod, Silver Spring, MD USA.
RP Keire, DA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO USA.; Aubin, Y (reprint author), Hlth Canada, Biol & Genet Therapies Directorate, Ctr Biol Evaluat, Ottawa, ON K1A 0L2, Canada.; Marino, JP (reprint author), NIST, Inst Biosci & Biotechnol Res, Rockville, MD USA.
EM john.marino@nist.gov; yves.aubin@hc-sc.gc.ca; david.keire@fda.hhs.gov
FU Intramural NIST DOC [9999-NIST]
NR 10
TC 4
Z9 4
U1 4
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
EI 1546-1696
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD FEB
PY 2016
VL 34
IS 2
BP 139
EP 141
DI 10.1038/nbt.3474
PG 3
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA DD0OK
UT WOS:000369619100011
PM 26849514
ER
PT J
AU Hansen, C
Andrade, SE
Freiman, H
Dublin, S
Haffenreffer, K
Cooper, WO
Cheetham, TC
Toh, S
Li, DK
Raebel, MA
Kuntz, JL
Perrin, N
Rosales, AG
Carter, S
Pawloski, PA
Maloney, EM
Graham, DJ
Sahin, L
Scott, PE
Yap, J
Davis, R
AF Hansen, Craig
Andrade, Susan E.
Freiman, Heather
Dublin, Sascha
Haffenreffer, Katie
Cooper, William O.
Cheetham, T. Craig
Toh, Sengwee
Li, De-Kun
Raebel, Marsha A.
Kuntz, Jennifer L.
Perrin, Nancy
Rosales, A. Gabriela
Carter, Shelley
Pawloski, Pamala A.
Maloney, Elizabeth M.
Graham, David J.
Sahin, Leyla
Scott, Pamela E.
Yap, John
Davis, Robert
TI Trimethoprim-sulfonamide use during the first trimester of pregnancy and
the risk of congenital anomalies
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Article
DE medications; pregnancy; birth defects; sulfonamides; antibacterial
agents; pharmacoepidemiology
ID FOLIC-ACID ANTAGONISTS; URINARY-TRACT-INFECTIONS;
BIRTH-DEFECTS-PREVENTION; DISEASES SOCIETY; MALFORMATIONS; ASSOCIATION;
GUIDELINES; EXPOSURE; AMERICA; CLEFTS
AB BackgroundSulfonamide antibacterials are widely used in pregnancy, but evidence about their safety is mixed. The objective of this study was to assess the association between first-trimester sulfonamide exposure and risk of specific congenital malformations.
MethodsMother-infant pairs were selected from a cohort of 1.2 million live-born deliveries (2001-2008) at 11 US health plans comprising the Medication Exposure in Pregnancy Risk Evaluation Program. Mothers with first-trimester trimethoprim-sulfonamide (TMP-SUL) exposures were randomly matched 1:1 to (i) a primary comparison group (mothers exposed to penicillins and/or cephalosporins) and (ii) a secondary comparison group (mothers with no dispensing of an antibacterial, antiprotozoal, or antimalarial medication during the same time period). The outcomes were cardiovascular abnormalities, cleft palate/lip, clubfoot, and urinary tract abnormalities.
ResultsWe first identified 7615 infants in the TMP-SUL exposure group, of which 7595 (99%) were exposed to a combination of TMP-SUL and the remaining 1% to sulfonamides alone. After matching (1:1) to the comparator groups and only including those with complete data on covariates, there were 20064 (n=6688 per group) in the primary analyses. Overall, cardiovascular defects (1.52%) were the most common and cleft lip/palate (0.10%) the least common that were evaluated. Compared with penicillin/cephalosporin exposure, and no antibacterial exposure, TMP-SUL exposure was not associated with statistically significant elevated risks for cardiovascular, cleft lip/palate, clubfoot, or urinary system defects.
ConclusionsFirst-trimester TMP-SUL exposure was not associated with a higher risk of the congenital anomalies studied, compared with exposure to penicillins and/or cephalosporins, or no exposure to antibacterials. Copyright (c) 2015 John Wiley & Sons, Ltd.
C1 [Hansen, Craig; Freiman, Heather; Davis, Robert] Kaiser Permanente Georgia, Ctr Clin & Outcomes Res, Atlanta, GA USA.
[Hansen, Craig] South Australian Hlth & Med Res Inst, Adelaide, SA, Australia.
[Andrade, Susan E.] Univ Massachusetts, Med Sch Worcester, Meyers Primary Care Inst, Worcester, MA 01605 USA.
[Freiman, Heather] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA.
[Dublin, Sascha] Grp Hlth Res Inst, Seattle, WA USA.
[Haffenreffer, Katie; Toh, Sengwee] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA.
[Haffenreffer, Katie; Toh, Sengwee] Harvard Pilgrim Hlth Care Inst, Boston, MA USA.
[Cooper, William O.] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA.
[Cooper, William O.] Vanderbilt Univ, Sch Med, Dept Hlth Policy, Nashville, TN 37212 USA.
[Cheetham, T. Craig] Kaiser Permanente So Calif, Pharm Analyt Serv, Downey, CA USA.
[Li, De-Kun] Kaiser Permanente, Kaiser Fdn Res Inst, Div Res, Oakland, CA USA.
[Raebel, Marsha A.] Kaiser Permanente, Colorado Inst Hlth Res, Denver, CO USA.
[Kuntz, Jennifer L.; Perrin, Nancy; Rosales, A. Gabriela] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR USA.
[Carter, Shelley] LCF Res, Albuquerque, NM USA.
[Pawloski, Pamala A.] Hlth Partners Inst Educ & Res, Minneapolis, MN USA.
[Maloney, Elizabeth M.; Graham, David J.] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA.
[Sahin, Leyla] US FDA, Off New Drugs, Silver Spring, MD USA.
[Scott, Pamela E.] US FDA, Off Womens Hlth, Silver Spring, MD USA.
[Yap, John] US FDA, Off Biostat, Silver Spring, MD USA.
[Davis, Robert] Univ Tennessee, Ctr Biomed Informat, Memphis, TN USA.
[Davis, Robert] Univ Tennessee, Dept Pediat, Memphis, TN USA.
RP Andrade, SE (reprint author), Univ Massachusetts, Med Sch Worcester, Meyers Primary Care Inst, Worcester, MA 01605 USA.
EM sandrade@meyersprimary.org
RI Toh, Sengwee/D-7567-2017
OI Toh, Sengwee/0000-0002-5160-0810
FU NIA NIH HHS [K23 AG028954]; PHS HHS [HHSF2232010000029I]
NR 31
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-8569
EI 1099-1557
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD FEB
PY 2016
VL 25
IS 2
BP 170
EP 178
DI 10.1002/pds.3919
PG 9
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA DD6TA
UT WOS:000370056200007
PM 26599424
ER
PT J
AU Pacanowski, M
Huang, SM
AF Pacanowski, M.
Huang, S. M.
TI Precision Medicine
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Editorial Material
C1 [Pacanowski, M.; Huang, S. M.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA.
RP Pacanowski, M (reprint author), US FDA, Off Clin Pharmacol, Silver Spring, MD USA.
EM Michael.Pacanowski@fda.hhs.gov
NR 15
TC 4
Z9 4
U1 1
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
IS 2
BP 124
EP 129
DI 10.1002/cpt.296
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DC9HW
UT WOS:000369533100001
PM 26800326
ER
PT J
AU Jang, SH
Yan, Z
Lazor, JA
AF Jang, S. H.
Yan, Z.
Lazor, J. A.
TI Therapeutic drug monitoring: A patient management tool for precision
medicine
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Editorial Material
ID INVASIVE FUNGAL-INFECTIONS
AB The precision medicine initiative is designed to better understand the causes of disease, to develop target therapies, and to identify patients that would benefit from treatment. Prescribing the right dose, which is not always the same to all patients, is needed for a successful outcome. The purpose of this commentary is to discuss the role of dose individualization based on therapeutic drug monitoring as a clinical patient management tool in the application of precision medicine.
C1 [Jang, S. H.; Yan, Z.; Lazor, J. A.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Jang, SH (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
EM seong.jang@fda.hhs.gov
NR 10
TC 5
Z9 5
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
IS 2
BP 148
EP 150
DI 10.1002/cpt.298
PG 3
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DC9HW
UT WOS:000369533100011
PM 26565378
ER
PT J
AU Woodcock, J
AF Woodcock, J.
TI "Precision" drug development?
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Editorial Material
AB The concept of precision medicine has entered broad public consciousness, spurred by a string of targeted drug approvals, highlighted by the availability of personal gene sequences, and accompanied by some remarkable claims about the future of medicine. It is likely that precision medicines will require precision drug development programs. What might such programs look like?
C1 [Woodcock, J.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Woodcock, J (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
EM janet.woodcock@fda.hhs.gov
NR 1
TC 1
Z9 1
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
IS 2
BP 152
EP 154
DI 10.1002/cpt.255
PG 3
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DC9HW
UT WOS:000369533100013
PM 26331240
ER
PT J
AU Woosley, RL
Whyte, J
Mohamadi, A
Romero, K
AF Woosley, R. L.
Whyte, J.
Mohamadi, A.
Romero, K.
TI Medical decision support systems and therapeutics: The role of
autopilots
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Editorial Material
ID TORSADE-DE-POINTES; RISK
AB For decades, medical practice has increasingly relied on prescription medicines to treat, cure, or prevent illness but their net benefit is reduced by prescribing errors that result in adverse drug reactions (ADRs) and tens of thousands of deaths each year. Optimal prescribing requires effective management of massive amounts of data. Clinical decision support systems (CDSS) can help manage information and support optimal therapeutic decisions before errors are made by operating as the prescribers' autopilot.
C1 [Woosley, R. L.] AZCERT Inc, Oro Valley, AZ USA.
[Woosley, R. L.] Univ Arizona, Coll Med, Phoenix, AZ USA.
[Whyte, J.; Mohamadi, A.] US FDA, Safe Use Initiat, Silver Spring, MD USA.
[Romero, K.] Crit Path Inst, Clin Pharmacol, Tucson, AZ USA.
RP Woosley, RL (reprint author), AZCERT Inc, Oro Valley, AZ USA.; Woosley, RL (reprint author), Univ Arizona, Coll Med, Phoenix, AZ USA.
EM rwoosley@azcert.org
OI Woosley, Raymond L./0000-0002-2588-328X
NR 10
TC 6
Z9 7
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
IS 2
BP 161
EP 164
DI 10.1002/cpt.259
PG 4
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DC9HW
UT WOS:000369533100016
PM 26352903
ER
PT J
AU Kalman, LV
Agundez, JAG
Appell, ML
Black, JL
Bell, GC
Boukouvala, S
Bruckner, C
Bruford, E
Caudle, K
Coulthard, SA
Daly, AK
Del Tredici, AL
den Dunnen, JT
Drozda, K
Everts, RE
Flockhart, D
Freimuth, RR
Gaedigk, A
Hachad, H
Hartshorne, T
Ingelman-Sundberg, M
Klein, TE
Lauschke, VM
Maglott, DR
McLeod, HL
McMillin, GA
Meyer, UA
Muller, DJ
Nickerson, DA
Oetting, WS
Pacanowski, M
Pratt, VM
Relling, MV
Roberts, A
Rubinstein, WS
Sangkuhl, K
Schwab, M
Scott, SA
Sim, SC
Thirumaran, RK
Toji, LH
Tyndale, RF
van Schaik, RHN
Whirl-Carrillo, M
Yeo, KTJ
Zanger, UM
AF Kalman, L. V.
Agundez, J. A. G.
Appell, M. Lindqvist
Black, J. L.
Bell, G. C.
Boukouvala, S.
Bruckner, C.
Bruford, E.
Caudle, K.
Coulthard, S. A.
Daly, A. K.
Del Tredici, A. L.
den Dunnen, J. T.
Drozda, K.
Everts, R. E.
Flockhart, D.
Freimuth, R. R.
Gaedigk, A.
Hachad, H.
Hartshorne, T.
Ingelman-Sundberg, M.
Klein, T. E.
Lauschke, V. M.
Maglott, D. R.
McLeod, H. L.
McMillin, G. A.
Meyer, U. A.
Mueller, D. J.
Nickerson, D. A.
Oetting, W. S.
Pacanowski, M.
Pratt, V. M.
Relling, M. V.
Roberts, A.
Rubinstein, W. S.
Sangkuhl, K.
Schwab, M.
Scott, S. A.
Sim, S. C.
Thirumaran, R. K.
Toji, L. H.
Tyndale, R. F.
van Schaik, R. H. N.
Whirl-Carrillo, M.
Yeo, K. T. J.
Zanger, U. M.
TI Pharmacogenetic allele nomenclature: International workgroup
recommendations for test result reporting
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID PERSONALIZED MEDICINE; IMPLEMENTATION CONSORTIUM; MOLECULAR-PATHOLOGY;
VKORC1 HAPLOTYPES; CLINICAL-PRACTICE; DRUG DEVELOPMENT; INFORMATION;
PERSPECTIVE; ASSOCIATION; TRANSPORTER
AB This article provides nomenclature recommendations developed by an international workgroup to increase transparency and standardization of pharmacogenetic (PGx) result reporting. Presently, sequence variants identified by PGx tests are described using different nomenclature systems. In addition, PGx analysis may detect different sets of variants for each gene, which can affect interpretation of results. This practice has caused confusion and may thereby impede the adoption of clinical PGx testing. Standardization is critical to move PGx forward.
C1 [Kalman, L. V.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Agundez, J. A. G.] Univ Extremadura, Dept Pharmacol, Caceres, Spain.
[Appell, M. Lindqvist] Linkoping Univ, Fac Med & Hlth Sci, Dept Med & Hlth Sci, Div Drug Res, Linkoping, Sweden.
[Black, J. L.; Freimuth, R. R.] Mayo Clin, Rochester, MN USA.
[Bell, G. C.; McLeod, H. L.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
[Boukouvala, S.] Democritus Univ Thrace, Dept Mol Biol & Genet, Alexandroupolis, Greece.
[Bruckner, C.] Affymetrix, Santa Clara, CA USA.
[Bruford, E.] European Mol Biol Lab, EMBL EBI, HUGO Gene Nomenclature Comm, Wellcome Genome Campus, Hinxton, England.
[Caudle, K.; Relling, M. V.] St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Coulthard, S. A.; Daly, A. K.] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Del Tredici, A. L.] Millennium Hlth LLC, San Diego, CA USA.
[den Dunnen, J. T.] Leiden Univ, Med Ctr, Dept Human Genet & Clin Genet, Leiden, Netherlands.
[Drozda, K.; Pacanowski, M.] US FDA, Silver Spring, MD USA.
[Everts, R. E.] Agena Biosci, San Diego, CA USA.
[Flockhart, D.; Pratt, V. M.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Gaedigk, A.] Univ Missouri, Childrens Mercy Kansas City, Div Clin Pharmacol & Therapeut Innovat, Kansas City, MO 64110 USA.
[Gaedigk, A.] Univ Missouri, Sch Med, Kansas City, MO 64108 USA.
[Hachad, H.] Translat Software, Bellevue, WA USA.
[Hartshorne, T.] Thermo Fisher Sci, Dept Genet Anal, San Francisco, CA USA.
[Ingelman-Sundberg, M.; Lauschke, V. M.; Sim, S. C.] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
[Klein, T. E.; Sangkuhl, K.; Whirl-Carrillo, M.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
[Maglott, D. R.; Rubinstein, W. S.] Natl Lib Med, NIH, Natl Ctr Biotechnol Informat, Bethesda, MD USA.
[McMillin, G. A.] Univ Utah, Salt Lake City, UT USA.
[McMillin, G. A.] ARUP Labs, Salt Lake City, UT USA.
[Meyer, U. A.] Univ Basel, Basel, Switzerland.
[Mueller, D. J.] Univ Toronto, Dept Psychiat, CAMH, Toronto, ON, Canada.
[Nickerson, D. A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Oetting, W. S.] Univ Minnesota, Dept Expt & Clin Pharmacol, Minneapolis, MN USA.
[Roberts, A.] Aegis Sci Corp, Nashville, TN USA.
[Schwab, M.; Zanger, U. M.] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Auerbachstr 112, Stuttgart, Germany.
[Schwab, M.; Zanger, U. M.] Univ Hosp, Dept Clin Pharmacol, Tubingen, Germany.
[Scott, S. A.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
[Thirumaran, R. K.] Genelex Corp, Seattle, WA USA.
[Toji, L. H.] Coriell Inst Med Res, Camden, NJ USA.
[Tyndale, R. F.] Univ Toronto, CAMH, Toronto, ON, Canada.
[Tyndale, R. F.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada.
[Tyndale, R. F.] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON, Canada.
[van Schaik, R. H. N.] Erasmus MC, Dept Clin Chem, Int Federat Clin Chem IFCC Task Force Pharmacogen, Rotterdam, Netherlands.
[Yeo, K. T. J.] Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA.
RP Kalman, LV (reprint author), Ctr Dis Control & Prevent, Atlanta, GA USA.
EM LKalman@cdc.gov
RI Agundez, Jose/A-5503-2008; Mueller, Daniel/L-4159-2016; Zanger,
Ulrich/A-9364-2012; Daly, Ann/H-3144-2011;
OI Mueller, Daniel/0000-0003-4978-4400; Zanger, Ulrich/0000-0002-5276-2002;
Daly, Ann/0000-0002-7321-0629; Agundez, Jose/0000-0001-6895-9160;
Bruford, Elspeth/0000-0002-8380-5247; Lauschke,
Volker/0000-0002-1140-6204
FU Intramural CDC HHS [CC999999]; NCI NIH HHS [P30 CA021765]; NHGRI NIH HHS
[U01 HG007762, U01HG007762, U41 HG003345, U41HG003345]; NIDA NIH HHS
[R01 DA035736]; NIGMS NIH HHS [R24GM115264, 2 R01 GM088076-05, K23
GM104401, R01 GM088076, R24 GM061374, R24 GM115264, R24 GM61374, U19
GM061388, U19 GM61388]; Wellcome Trust [099129/Z/12/Z]
NR 54
TC 8
Z9 9
U1 6
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
IS 2
BP 172
EP 185
DI 10.1002/cpt.280
PG 14
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DC9HW
UT WOS:000369533100020
PM 26479518
ER
PT J
AU Vicini, P
Fields, O
Lai, E
Litwack, ED
Martin, AM
Morgan, TM
Pacanowski, MA
Papaluca, M
Perez, OD
Ringel, MS
Robson, M
Sakul, H
Vockley, J
Zaks, T
Dolsten, M
Sogaard, M
AF Vicini, P.
Fields, O.
Lai, E.
Litwack, E. D.
Martin, A-M
Morgan, T. M.
Pacanowski, M. A.
Papaluca, M.
Perez, O. D.
Ringel, M. S.
Robson, M.
Sakul, H.
Vockley, J.
Zaks, T.
Dolsten, M.
Sogaard, M.
TI Precision medicine in the age of big data: The present and future role
of large-scale unbiased sequencing in drug discovery and development
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Review
ID PERSONALIZED MEDICINE; STRATIFIED MEDICINE; INCIDENTAL FINDINGS;
COMPANION DIAGNOSTICS; CLINICAL GENOME; CANCER; CHALLENGES; PROJECT;
EXOME; RECOMMENDATIONS
AB High throughput molecular and functional profiling of patients is a key driver of precision medicine. DNA and RNA characterization has been enabled at unprecedented cost and scale through rapid, disruptive progress in sequencing technology, but challenges persist in data management and interpretation. We analyze the state-of-the-art of large-scale unbiased sequencing in drug discovery and development, including technology, application, ethical, regulatory, policy and commercial considerations, and discuss issues of LUS implementation in clinical and regulatory practice.
C1 [Vicini, P.; Fields, O.; Perez, O. D.; Sakul, H.; Dolsten, M.; Sogaard, M.] Pfizer Worldwide Res & Dev, La Jolla, CA USA.
[Vicini, P.; Fields, O.; Perez, O. D.; Sakul, H.; Dolsten, M.; Sogaard, M.] Pfizer Worldwide Res & Dev, Collegeville, PA USA.
[Vicini, P.; Fields, O.; Perez, O. D.; Sakul, H.; Dolsten, M.; Sogaard, M.] Pfizer Worldwide Res & Dev, New York, NY USA.
[Fields, O.] Takeda Pharmaceut Int, Deerfield, IL USA.
[Litwack, E. D.; Pacanowski, M. A.] US FDA, Silver Spring, MD USA.
[Martin, A-M] GlaxoSmithKline, Collegeville, PA USA.
[Morgan, T. M.; Robson, M.] Novartis Inst Biomed Res, Cambridge, MA USA.
[Morgan, T. M.; Robson, M.] Novartis Inst Biomed Res, E Hanover, NJ USA.
[Papaluca, M.] European Med Agcy, London, England.
[Ringel, M. S.] Boston Consulting Grp Inc, Boston, MA USA.
[Vockley, J.] Inova Translat Med Inst, Falls Church, VA USA.
[Zaks, T.] Sanofi, Cambridge, MA USA.
RP Sogaard, M (reprint author), Pfizer Worldwide Res & Dev, La Jolla, CA USA.; Sogaard, M (reprint author), Pfizer Worldwide Res & Dev, Collegeville, PA USA.
EM morten.sogaard@pfizer.com
NR 74
TC 5
Z9 6
U1 9
U2 34
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
IS 2
BP 198
EP 207
DI 10.1002/cpt.293
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DC9HW
UT WOS:000369533100022
PM 26536838
ER
PT J
AU Johannesen, L
Vicente, J
Mason, JW
Erato, C
Sanabria, C
Waite-Labott, K
Hong, M
Lin, J
Guo, P
Mutlib, A
Wang, J
Crumb, WJ
Blinova, K
Chan, D
Stohlman, J
Florian, J
Ugander, M
Stockbridge, N
Strauss, DG
AF Johannesen, L.
Vicente, J.
Mason, J. W.
Erato, C.
Sanabria, C.
Waite-Labott, K.
Hong, M.
Lin, J.
Guo, P.
Mutlib, A.
Wang, J.
Crumb, W. J.
Blinova, K.
Chan, D.
Stohlman, J.
Florian, J.
Ugander, M.
Stockbridge, N.
Strauss, D. G.
TI Late sodium current block for drug-induced long QT syndrome: Results
from a prospective clinical trial
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID TORSADE-DE-POINTES; VENTRICULAR-ARRHYTHMIAS; MULTICHANNEL BLOCK;
POTASSIUM CHANNEL; MEXILETINE; LIDOCAINE; QUINIDINE; HERG; COMBINATION;
INTERVAL
AB Drug-induced long QT syndrome has resulted in many drugs being withdrawn from the market. At the same time, the current regulatory paradigm for screening new drugs causing long QT syndrome is preventing drugs from reaching the market, sometimes inappropriately. In this study, we report the results of a first-of-a-kind clinical trial studying late sodium (mexiletine and lidocaine) and calcium (diltiazem) current blocking drugs to counteract the effects of hERG potassium channel blocking drugs (dofetilide and moxifloxacin). We demonstrate that both mexiletine and lidocaine substantially reduce heart-rate corrected QT (QTc) prolongation from dofetilide by 20 ms. Furthermore, all QTc shortening occurs in the heart-rate corrected J-T-peak (J-T(peak)c) interval, the biomarker we identified as a sign of late sodium current block. This clinical trial demonstrates that late sodium blocking drugs can substantially reduce QTc prolongation from hERG potassium channel block and assessment of J-T(peak)c may add value beyond only assessing QTc.
C1 [Johannesen, L.; Vicente, J.; Blinova, K.; Chan, D.; Stohlman, J.; Ugander, M.; Strauss, D. G.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Johannesen, L.; Ugander, M.; Strauss, D. G.] Karolinska Inst, Dept Clin Physiol, S-10401 Stockholm, Sweden.
[Johannesen, L.; Ugander, M.; Strauss, D. G.] Karolinska Univ Hosp, Stockholm, Sweden.
[Vicente, J.; Florian, J.; Stockbridge, N.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Vicente, J.] Univ Zaragoza, IIS Aragon, Aragon Inst Engn Res I3A, BSICoS Grp, Zaragoza, Spain.
[Mason, J. W.; Erato, C.; Sanabria, C.; Waite-Labott, K.] Spaulding Clin, West Bend, WI USA.
[Mason, J. W.] Univ Utah, Salt Lake City, UT USA.
[Hong, M.; Lin, J.; Guo, P.; Mutlib, A.; Wang, J.] Frontage Labs, Exton, PA USA.
[Crumb, W. J.] Zenas Technol, Metairie, LA USA.
RP Strauss, DG (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.; Strauss, DG (reprint author), Karolinska Inst, Dept Clin Physiol, S-10401 Stockholm, Sweden.; Strauss, DG (reprint author), Karolinska Univ Hosp, Stockholm, Sweden.
EM David.Strauss@fda.hhs.gov
OI Ugander, Martin/0000-0003-3665-2038; Vicente, Jose/0000-0001-9963-1205
NR 38
TC 14
Z9 14
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
IS 2
BP 214
EP 223
DI 10.1002/cpt.205
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DC9HW
UT WOS:000369533100024
PM 26259627
ER
PT J
AU Coleman, BN
Johnson, SE
Tessrnan, GK
Tworek, C
Alexander, J
Dickinson, DM
Rath, J
Green, KM
AF Coleman, Blair N.
Johnson, Sarah E.
Tessrnan, Greta K.
Tworek, Cindy
Alexander, Jennifer
Dickinson, Denise M.
Rath, Jessica
Green, Kerry M.
TI "It's not smoke. It's not tar. It's not 4000 chemicals. Case closed":
Exploring attitudes, beliefs, and perceived social norms of e-cigarette
use among adult users
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Electronic cigarettes; Qualitative research; Tobacco use
ID NICOTINE DELIVERY-SYSTEMS; ELECTRONIC CIGARETTES; HARM PERCEPTIONS;
AWARENESS; BENEFITS; REASONS
AB Background: Electronic cigarette (e-cigarette) use is rapidly increasing among adults in the U.S. The purpose of this qualitative study was to explore consumer perceptions about e-cigarettes, including knowledge, attitudes, beliefs and perceived social norms.
Methods: A total of 14 focus groups (N=116) were conducted with current adult e-cigarette users in five U.S. cities from March through May, 2014. Focus groups were segmented by age (young adults aged 18-29 and older adults aged 30 and older) as well as by e-cigarette use status (exclusive e-cigarette users and non-exclusive e-cigarette users). Focus group discussions lasted approximately 60-min and were audio-recorded and transcribed; data were analyzed using a phenomenological approach.
Results: Participants expressed many positive attitudes towards e-cigarettes and simultaneously reported a lack of information and knowledge about the products. Focus group participants overwhelmingly felt as though the ingredients of e-cigarettes were likely less harmful than conventional cigarettes. Additionally, many described positive reactions from family and friends, especially when e-cigarettes were used in place of conventional cigarettes.
Conclusions: Findings from this qualitative study provide insight into consumer knowledge, attitudes and beliefs about e-cigarettes increasing our understanding of why and how they are being used. Such information will help provide insight into the potential public health impact of these emerging products. Published by Elsevier Ireland Ltd.
C1 [Coleman, Blair N.; Johnson, Sarah E.; Tessrnan, Greta K.; Tworek, Cindy] US FDA, Ctr Tobacco Prod, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
[Alexander, Jennifer; Dickinson, Denise M.] RTI Int, 3040 E Cornwallis Rd, Res Triangle Pk, NC 27709 USA.
[Rath, Jessica] Truth Initiat Evaluat Sci & Res, 900 G St NW,Fourth Floor, Washington, DC 20001 USA.
[Green, Kerry M.] Univ Maryland, Sch Publ Hlth, Dept Behav & Community Hlth, 2242 Valley Dr, College Pk, MD 20742 USA.
RP Coleman, BN (reprint author), US FDA, Ctr Tobacco Prod, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM Blair.Coleman@fda.hhs.gov
FU U.S. Food and Drug Administration (FDA) Center for Tobacco Products
(CTP)
FX Funding for data collection and analysis was provided by the U.S. Food
and Drug Administration (FDA) Center for Tobacco Products (CTP).
NR 22
TC 6
Z9 6
U1 11
U2 27
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
EI 1879-0046
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD FEB 1
PY 2016
VL 159
BP 80
EP 85
DI 10.1016/j.drugalcdep.2015.11.028
PG 6
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA DC8LX
UT WOS:000369472200011
PM 26708706
ER
PT J
AU McCormack, L
Lefebvre, RC
Bann, C
Taylor, O
Rausch, P
AF McCormack, Lauren
Lefebvre, R. Craig
Bann, Carla
Taylor, Olivia
Rausch, Paula
TI Consumer Understanding, Preferences, and Responses to Different Versions
of Drug Safety Messages in the United States: A Randomized Controlled
Trial
SO DRUG SAFETY
LA English
DT Article
ID RISK COMMUNICATION; HEALTH LITERACY; FDA; READABILITY; INSTRUMENT;
FUTURE
AB Introduction As part of its mission, the US Food and Drug Administration (FDA) communicates with the public regularly about the benefits and risks of prescription and over-the-counter (OTC) drugs. Effectively communicating risk, however, is a significant public health challenge.
Objective To better understand how different populations understand information communicated by the FDA about drug safety, we conducted a randomized experiment to examine comprehension and other measures of effectiveness of drug safety messages that occurred in a post-market surveillance phase.
Methods We used an Internet panel survey of 1244 consumers, of whom 58 % used prescription drugs in the past year. Half of the sample panel was randomized to read a previous FDA Drug Safety Communication (DSC) with the drug name changed, and the other half was randomized to read a revised version of the same DSC. We examined how making certain modifications to the way drug risk information is communicated has an impact on comprehension and behavioral intentions, including the user's likelihood of discontinuing the drug. We also studied how comprehension varied by respondent characteristics, health literacy skills, risk perceptions, and trust in the message.
Results Based on a five-item comprehension index, the revised version of the message was associated with significantly greater comprehension of the information relative to the standard version (63 vs 52 % correct, p < 0.001). Significantly more respondents found the revised version to be clear (82 vs 73 %, p < 0.000), while fewer in that group reported learning something new (78 % vs 84 %, p = 0.015). No significant differences emerged between the two groups in terms of the message being informative, convincing, or helpful. We found no significant differences between the two groups in terms of behavioral intentions, risk perception, and trust.
Conclusions We found that making plain language changes to the DSC significantly increased consumers' level of comprehension of its content, providing support for ongoing use and further exploration of these strategies in pharmacovigilance communication research. The study findings have important implications for future drug safety and other communication messages related to prescription drugs.
C1 [McCormack, Lauren; Lefebvre, R. Craig; Taylor, Olivia] RTI Int, Ctr Commun Sci, 3040 East Cornwallis Rd, Res Triangle Pk, NC 27709 USA.
[Bann, Carla] RTI Int, Div Stat & Data Sci, Res Triangle Pk, NC 27709 USA.
[Rausch, Paula] US FDA, Ctr Drug Evaluat & Res, Off Commun, Silver Spring, MD USA.
RP McCormack, L (reprint author), RTI Int, Ctr Commun Sci, 3040 East Cornwallis Rd, Res Triangle Pk, NC 27709 USA.
EM lmac@rti.org
FU US Food and Drug Administration, Center for Drug Evaluation and
Research, Office of Communications [1 U18 FD004608-01]
FX The US Food and Drug Administration, Center for Drug Evaluation and
Research, Office of Communications funded and participated in all phases
of this project through a cooperative agreement with RTI International,
award #1 U18 FD004608-01. The contents of this article are solely the
responsibility of the authors and do not necessarily represent the
official views of the FDA, CDER, or the US Department of Health and
Human Services.
NR 36
TC 2
Z9 2
U1 3
U2 7
PU ADIS INT LTD
PI NORTHCOTE
PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND
SN 0114-5916
EI 1179-1942
J9 DRUG SAFETY
JI Drug Saf.
PD FEB
PY 2016
VL 39
IS 2
BP 171
EP 184
DI 10.1007/s40264-015-0358-9
PG 14
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy;
Toxicology
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy;
Toxicology
GA DC5YB
UT WOS:000369295500007
PM 26547718
ER
PT J
AU Choi, M
Ghammraoui, B
Badal, A
Badano, A
AF Choi, Mina
Ghammraoui, Bahaa
Badal, Andreu
Badano, Aldo
TI Monte Carlo X-ray transport simulation of small-angle X-ray scattering
instruments using measured sample cross sections
SO JOURNAL OF APPLIED CRYSTALLOGRAPHY
LA English
DT Article
DE small-angle X-ray scattering; empirical cross sections; Monte Carlo
simulations; molecular interactions
AB Small-angle X-ray scattering (SAXS) has recently been proposed as a novel noninvasive in vivo molecular imaging technique to characterize molecular interactions deep within the body using high-contrast probes. This article describes a detailed Monte Carlo X-ray transport simulation technique that utilizes user-provided cross sections to describe X-ray interaction in virtual samples and explore SAXS instrument design choices. The accuracy of the simulation code is validated with sample material cross sections derived from analytical models and empirical measurements of a homogeneous spherical gold nanoparticle (GNP) monomer, a dimer and heterogeneous mixtures of the two in aqueous solution. Analytical and measured scattering profiles from these samples were converted to cross sections using an absolute water standard. Our Monte Carlo estimates of the fraction of dimers from analytically derived and empirically derived cross sections are strongly correlated, with less than 1.5 and 16% error, respectively, to the expected concentration of monomer and dimer species. In addition, a variety of monoenergetic X-ray beams were simulated to investigate coherent scattering versus radiation dose for a range of sample sizes. For GNP spheres in aqueous solution, the energy range that produces the most coherent scattering at the detector per deposited energy was between 31 and 49 keV for a sample thickness of 1 mm to 10 cm. The method described here for the detailed simulation of SAXS using measured and modeled cross sections will enable instrumentation optimization for in vivo molecular imaging applications.
C1 [Choi, Mina; Ghammraoui, Bahaa; Badal, Andreu; Badano, Aldo] US FDA, Div Imaging Diagnost & Software Reliabil, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
[Choi, Mina; Badano, Aldo] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA.
RP Badano, A (reprint author), US FDA, Div Imaging Diagnost & Software Reliabil, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.; Badano, A (reprint author), Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA.
EM aldo.badano@fda.hhs.gov
OI badano, aldo/0000-0003-3712-6670
FU Fischell Fellowship in Biomedical Engineering; FDA Medical
Countermeasures Initiative (MCMi)
FX MC was supported by the Fischell Fellowship in Biomedical Engineering.
This work was supported by the FDA Medical Countermeasures Initiative
(MCMi). The mention of commercial products herein is not to be construed
as either an actual or an implied endorsement of such products by the
Department of Health and Human Services. This is a contribution of the
US Food and Drug Administration and is not subject to copyright.
NR 15
TC 0
Z9 0
U1 2
U2 2
PU INT UNION CRYSTALLOGRAPHY
PI CHESTER
PA 2 ABBEY SQ, CHESTER, CH1 2HU, ENGLAND
SN 1600-5767
J9 J APPL CRYSTALLOGR
JI J. Appl. Crystallogr.
PD FEB
PY 2016
VL 49
BP 188
EP 194
DI 10.1107/S1600576715023924
PN 1
PG 7
WC Chemistry, Multidisciplinary; Crystallography
SC Chemistry; Crystallography
GA DC7HB
UT WOS:000369389300022
ER
PT J
AU Morgan, SJ
French, EL
Thomson, JJ
Seaborn, CP
Shively, CA
Krukonis, ES
AF Morgan, Sarah J.
French, Emily L.
Thomson, Joshua J.
Seaborn, Craig P.
Shively, Christian A.
Krukonis, Eric S.
TI Formation of an Intramolecular Periplasmic Disulfide Bond in TcpP
Protects TcpP and TcpH from Degradation in Vibrio cholerae
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID VIRULENCE GENE-EXPRESSION; REGULATED INTRAMEMBRANE PROTEOLYSIS;
TRANSCRIPTIONAL ACTIVATION; SIGNAL-TRANSDUCTION; ESCHERICHIA-COLI; TOXR
REGULON; DNA-BINDING; STRESS-RESPONSE; CELL-ENVELOPE; PROMOTER
AB TcpP and ToxR coordinately regulate transcription of toxT, the master regulator of numerous virulence factors in Vibrio cholerae. TcpP and ToxR are membrane-localized transcription factors, each with a periplasmic domain containing two cysteines. In ToxR, these cysteines form an intramolecular disulfide bond and a cysteine-to-serine substitution affects activity. We determined that the two periplasmic cysteines of TcpP also form an intramolecular disulfide bond. Disruption of this intramolecular disulfide bond by mutation of either cysteine resulted in formation of intermolecular disulfide bonds. Furthermore, disruption of the intramolecular disulfide bond in TcpP decreased the stability of TcpP. While the decreased stability of TcpP-C207S resulted in a nearly complete loss of toxT activation and cholera toxin (CT) production, the second cysteine mutant, TcpP-C218S, was partially resistant to proteolytic degradation and maintained similar to 50% toxT activation capacity. TcpP-C218S was also TcpH independent, since deletion of tcpH did not affect the stability of TcpP-C218S, whereas wild-type TcpP was degraded in the absence of TcpH. Finally, TcpH was also unstable when intramolecular disulfides could not be formed in TcpP, suggesting that the single periplasmic cysteine in TcpH may assist with disulfide bond formation in TcpP by interacting with the periplasmic cysteines of TcpP. Consistent with this finding, a TcpH-C114S mutant was unable to stabilize TcpP and was itself unstable. Our findings demonstrate a periplasmic disulfide bond in TcpP is critical for TcpP stability and virulence gene expression.
IMPORTANCE
The Vibrio cholerae transcription factor TcpP, in conjunction with ToxR, regulates transcription of toxT, the master regulator of numerous virulence factors in Vibrio cholerae. TcpP is a membrane-localized transcription factor with a periplasmic domain containing two cysteines. We determined that the two periplasmic cysteines of TcpP form an intramolecular disulfide bond and disruption of the intramolecular disulfide bond in TcpP decreased the stability of TcpP and reduced virulence gene expression. Normally TcpH, another membrane-localized periplasmic protein, protects TcpP from degradation. However, we found that TcpH was also unstable when intramolecular disulfides could not be formed in TcpP, indicating that the periplasmic cysteines of TcpP are required for functional interaction with TcpH and that this interaction is required for both TcpP and TcpH stability.
C1 [Morgan, Sarah J.; Seaborn, Craig P.; Krukonis, Eric S.] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
[French, Emily L.; Thomson, Joshua J.; Krukonis, Eric S.] Univ Detroit Mercy, Sch Dent, Dept Biomed & Diagnost Sci, Detroit, MI 48221 USA.
[Shively, Christian A.] Univ Michigan, Sch Med, Program Cell & Mol Biol, Ann Arbor, MI USA.
[Morgan, Sarah J.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
[Seaborn, Craig P.] Food & Drug Adm, Cincinnati, OH USA.
RP Krukonis, ES (reprint author), Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
EM krukones@udmercy.edu
FU HHS \ NIH \ National Institute of Allergy and Infectious Diseases
(NIAID) [AI075087]
FX HHS vertical bar NIH vertical bar National Institute of Allergy and
Infectious Diseases (NIAID) provided funding to Eric Krukonis under
grant number AI075087.
NR 48
TC 0
Z9 0
U1 1
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
EI 1098-5530
J9 J BACTERIOL
JI J. Bacteriol.
PD FEB
PY 2016
VL 198
IS 3
BP 498
EP 509
DI 10.1128/JB.00338-15
PG 12
WC Microbiology
SC Microbiology
GA DC4AY
UT WOS:000369163300015
ER
PT J
AU Wake, LM
Ahn, I
Farooqui, M
Hahn, J
Tian, X
Stetler-Stevenson, M
Marti, G
Wiestner, A
Maric, I
AF Wake, Laura M.
Ahn, Inhye
Farooqui, Mohammed
Hahn, Jamie
Tian, Xin
Stetler-Stevenson, Maryalice
Marti, Gerald
Wiestner, Adrian
Maric, Irina
TI Dual Antibody Immunohistochemistry: A Cost-Efficient and Sensitive New
Tool for the Detection of Minimal Residual CLL
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 105th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 12-18, 2016
CL Seattle, WA
SP US & Canadian Acad Pathol
C1 NCI, NIH, Bethesda, MD 20892 USA.
NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
NIH, CC, DLM, Bldg 10, Bethesda, MD 20892 USA.
US FDA, CDRH, Bethesda, MD 20014 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2016
VL 96
SU 1
MA 1507
BP 382A
EP 382A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA DC5OQ
UT WOS:000369270702246
ER
PT J
AU Song, Y
Zemlyanoy, D
Chen, X
Nie, HC
Su, ZY
Fang, K
Yang, XH
Smith, D
Byrn, S
Lubach, JW
AF Song, Yang
Zemlyanoy, Dmitry
Chen, Xin
Nie, Haichen
Su, Ziyang
Fang, Ke
Yang, Xinghao
Smith, Daniel
Byrn, Stephen
Lubach, Joseph W.
TI Acid-Base Interactions of Polystyrene Sulfonic Acid in Amorphous Solid
Dispersions Using a Combined UV/FTIR/XPS/ssNMR Study
SO MOLECULAR PHARMACEUTICS
LA English
DT Article
DE lapatinib; gefitinib; amorphous; solid dispersion; physical stability;
dissolution rate; XPS; solid-state NMR; ionic interaction; salt
ID HOT-MELT EXTRUSION; ANGLE-SPINNING NMR; STATE NMR; INTERMOLECULAR
INTERACTIONS; DIFFERENT POLYMERS; N-15 NMR; SPECTROSCOPY; STABILIZATION;
INDOMETHACIN; CRYSTALLIZATION
AB This study investigates the potential drug excipient interactions of polystyrene sulfonic acid (PSSA) and two weakly basic anticancer drugs, lapatinib (LB) and gefitinib (GB), in amorphous solid dispersions. Based on the strong acidity of the sulfonic acid functional group, PSSA was hypothesized to exhibit specific intermolecular acid base interactions with both model basic drugs. Ultraviolet (UV) spectroscopy identified red shifts, which correlated well with the color change observed in lapatinib PSSA solutions. Fourier transform infrared (FTIR) spectra suggest the protonation of the quinazoline nitrogen atom in both model compounds, which agrees well with data from the crystalline ditosylate salt of lapatinib. X-ray photoelectron spectroscopy (XPS) detected increases in binding energy of the basic nitrogen atoms in both lapatinib and gefitinib, strongly indicating protonation of these nitrogen atoms. N-15 solid-state NMR spectroscopy provided direct spectroscopic evidence for protonation of the quinazoline nitrogen atoms in both LB and GB, as well as the secondary amine nitrogen atom in LB and the tertiary amine nitrogen atom in GB. The observed chemical shifts in the LB PSSA N-15 spectrum also agree very well with the lapatinib ditosylate salt where proton transfer is known. Additionally, the dissolution and physical stability behaviors of both amorphous solid dispersions were examined. PSSA was found to significantly improve the dissolution of LB and GB and effectively inhibit the crystallization of LB and GB under accelerated storage conditions due to the beneficial strong intermolecular acid base interaction between the sulfonic acid groups and basic nitrogen centers.
C1 [Song, Yang; Nie, Haichen; Fang, Ke; Smith, Daniel; Byrn, Stephen] Purdue Univ, Dept Ind & Phys Pharm, W Lafayette, IN 47907 USA.
[Zemlyanoy, Dmitry] Purdue Univ, Birck Nanotechnol Ctr, W Lafayette, IN 47907 USA.
[Chen, Xin] GlaxoSmithKline, Collegeville, PA 19426 USA.
[Su, Ziyang] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Yang, Xinghao] Nanjing Normal Univ, Coll Life Sci, Nanjing 210046, Jiangsu, Peoples R China.
[Lubach, Joseph W.] Genentech Inc, Small Mol Pharmaceut Sci, San Francisco, CA 94080 USA.
RP Lubach, JW (reprint author), Genentech Inc, Small Mol Pharmaceut Sci, San Francisco, CA 94080 USA.
EM lubach.joseph@gene.com
NR 41
TC 3
Z9 3
U1 4
U2 25
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1543-8384
J9 MOL PHARMACEUT
JI Mol. Pharm.
PD FEB
PY 2016
VL 13
IS 2
BP 483
EP 492
DI 10.1021/acs.molpharmaceut.5b00708
PG 10
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA DC6VE
UT WOS:000369356900016
PM 26716395
ER
PT J
AU Bairi, VG
Lim, JH
Quevedo, IR
Mudalige, TK
Linder, SW
AF Bairi, Venu Gopal
Lim, Jin-Hee
Quevedo, Ivan R.
Mudalige, Thilak K.
Linder, Sean W.
TI Portable X-ray fluorescence spectroscopy as a rapid screening technique
for analysis of TiO2 and ZnO in sunscreens
SO SPECTROCHIMICA ACTA PART B-ATOMIC SPECTROSCOPY
LA English
DT Article
DE Sunscreens; Metals; Quantitation; Portable x-ray fluorescence
spectroscopy analyzer; Inductively coupled plasma-mass spectrometry
ID TITANIUM-DIOXIDE; ZINC-OXIDE; SPECTROMETRY; XRF; CONTROVERSIES;
INGREDIENTS; ANALYZER
AB This investigation reports a rapid and simple screening technique for the quantification of titanium and zinc in commercial sunscreens using portable X-ray fluorescence spectroscopy (pXRF). A highly evolved technique, inductively coupled plasma-mass spectroscopy (ICP-MS) was chosen as a comparative technique to pXRF, and a good correlation (r(2)> 0.995) with acceptable variations (525%) in results between both techniques was observed. Analytical figures of merit such as detection limit, quantitation limit, and linear range of the method are reported for the pXRF technique. This method has a good linearity (r(2) > 0.995) for the analysis of titanium (Ti) in the range of 0.4-14.23 wt%, and zinc (Zn) in the range of 1.0-23.90 wt%. However, most commercial sunscreens contain organic ingredients, and these ingredients are known to cause matrix effects. The development of appropriate matrix matched working standards to obtain the calibration curve was found to be a major challenge for the pXRF measurements. In this study, we have overcome the matrix effect by using metal-free commercial sunscreens as a dispersing media for the preparation of working standards. An easy extension of this unique methodology for preparing working standards in different matrices was also.reported. This method is simple, rapid, and cost-effective and, in comparison to conventional techniques (e.g., ICP-MS), did not generate toxic wastes during sample analysis. Published by Elsevier B.V.
C1 [Bairi, Venu Gopal; Lim, Jin-Hee; Quevedo, Ivan R.; Mudalige, Thilak K.; Linder, Sean W.] US FDA, Arkansas Reg Lab, Off Regulatory Affairs, 3900 NCTR Rd, Jefferson, AR 72079 USA.
RP Lim, JH; Linder, SW (reprint author), US FDA, Arkansas Reg Lab, Off Regulatory Affairs, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM Jin.Lim@fda.hhs.gov; Sean.Linder@fda.hhs.gov
FU Nanotechnology CORES (Collaborative Opportunities for Research
Excellence in Science) Program; U.S. Department of Energy; FDA
FX This work was performed at the Nanotechnology Core Facility (NanoCore)
located in the U.S. Food and Drug Administration's Jefferson
Laboratories campus (Jefferson, Arkansas), which also houses the FDA
National Center for Toxicological Research and the FDA Office of
Regulatory Affairs, Arkansas Regional Laboratory. This project was
graciously supported by Nanotechnology CORES (Collaborative
Opportunities for Research Excellence in Science) Program administered
by the FDA Office of Chief Scientist, and supported in part by an
appointment to the Research Participation Program at the Office of
Regulatory Affairs/Arkansas Regional Laboratory, U.S. FDA, administered
by the Oak Ridge Institute for Science and Education through an
interagency agreement between U.S. Department of Energy and FDA. The
views expressed in this manuscript are those of the authors and should
not be interpreted as the official opinion or policy of the U.S. Food
and Drug Administration, Department of Health and Human Services, or any
other agency or component of the U.S. government. The mention of trades
names, commercial products, or organizations is for clarification of the
methods used and should not be interpreted as an endorsement of a
product or manufacturer. We would like to thank Paul C. Howard, Lydia
Velazquez, Germarie Sanchez-Pomales, Patrick Sisco, Haiou Qu, Yasith
Nanayaldcara, and Nuwan Kothalawala for their support, valuable time,
and comments.
NR 32
TC 2
Z9 2
U1 9
U2 26
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0584-8547
J9 SPECTROCHIM ACTA B
JI Spectroc. Acta Pt. B-Atom. Spectr.
PD FEB 1
PY 2016
VL 116
BP 21
EP 27
DI 10.1016/j.sab.2015.11.008
PG 7
WC Spectroscopy
SC Spectroscopy
GA DC8JE
UT WOS:000369464900004
PM 27076699
ER
PT J
AU Xu, L
Ziegelbauer, J
Wang, R
Wu, WW
Shen, RF
Juhl, H
Zhang, YQ
Rosenberg, A
AF Xu, Lai
Ziegelbauer, Joseph
Wang, Rong
Wu, Wells W.
Shen, Rong-Fong
Juhl, Hartmut
Zhang, Yaqin
Rosenberg, Amy
TI Distinct Profiles for Mitochondrial t-RNAs and Small Nucleolar RNAs in
Locally Invasive and Metastatic Colorectal Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID BREAST-CANCER; RECTAL-CANCER; COLON-CANCER; EXPRESSION; HYPOXIA; GENES;
MICRORNA; PROLIFERATION; METABOLISM; BIOMARKERS
AB Purpose: To gain insight into factors involved in tumor progression and metastasis, we examined the role of noncoding RNAs in the biologic characteristics of colorectal carcinoma, in paired samples of tumor together with normal mucosa from the same colorectal carcinoma patient. The tumor and healthy tissue samples were collected and stored under stringent conditions, thereby minimizing warm ischemic time.
Experimental Design: We focused particularly on distinctions among high-stage tumors and tumors with known metastases, performing RNA-Seq analysis that quantifies transcript abundance and identifies novel transcripts.
Results: In comparing 35 colorectal carcinomas, including 9 metastatic tumors (metastases to lymph nodes and lymphatic vessels), with their matched healthy control mucosa, we found a distinct signature of mitochondrial transfer RNAs (MT-tRNA) and small nucleolar RNAs (snoRNA) for metastatic and high-stage colorectal carcinoma. We also found the following: (i) MT-TF (phenylalanine) and snord12B expression correlated with a substantial number of miRNAs and mRNAs in 14 colorectal carcinomas examined; (ii) an miRNA signature of oxidative stress, hypoxia, and a shift to glycolytic metabolism in 14 colorectal carcinomas, regardless of grade and stage; and (iii) heterogeneous MT-tRNA/snoRNA fingerprints for 35 pairs.
Conclusions: These findings could potentially assist in more accurate and predictive staging of colorectal carcinoma, including identification of those colorectal carcinomas likely to metastasize. (C)2015 AACR.
C1 [Xu, Lai; Wang, Rong; Zhang, Yaqin; Rosenberg, Amy] FDA, OBP DBRR 3, CDER, Silver Spring, MD USA.
[Ziegelbauer, Joseph] NCI, HIV AIDS Malignancy Branch, Bethesda, MD 20892 USA.
[Wu, Wells W.; Shen, Rong-Fong] FDA, Facil Biotechnol Resources, CBER, Silver Spring, MD USA.
[Juhl, Hartmut] Indivumed GMBH, Hamburg, Germany.
RP Rosenberg, A (reprint author), FDA, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA.
EM amy.rosenberg@fda.hhs.gov
OI Ziegelbauer, Joseph/0000-0001-6464-6941
FU Intramural NIH HHS [Z99 OD999999]
NR 34
TC 2
Z9 2
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD FEB 1
PY 2016
VL 22
IS 3
BP 773
EP 784
DI 10.1158/1078-0432.CCR-15-0737
PG 12
WC Oncology
SC Oncology
GA DC2XY
UT WOS:000369083300027
PM 26384739
ER
PT J
AU Cartwright, EJ
Nguyen, T
Melluso, C
Ayers, T
Lane, C
Hodges, A
Li, X
Quammen, J
Yendell, SJ
Adams, J
Mitchell, J
Rickert, R
Klos, R
Williams, IT
Behravesh, CB
Wright, J
AF Cartwright, E. J.
Nguyen, T.
Melluso, C.
Ayers, T.
Lane, C.
Hodges, A.
Li, X.
Quammen, J.
Yendell, S. J.
Adams, J.
Mitchell, J.
Rickert, R.
Klos, R.
Williams, I. T.
Behravesh, C. Barton
Wright, J.
TI A Multistate Investigation of Antibiotic-Resistant Salmonella enterica
Serotype I 4,[5],12:i:- Infections as Part of an International Outbreak
Associated with Frozen Feeder Rodents
SO ZOONOSES AND PUBLIC HEALTH
LA English
DT Article
DE Salmonella; outbreak; reptiles; frozen feeder rodents; zoonoses;
amphibians
ID MAIL-ORDER HATCHERY; UNITED-STATES; LIVE POULTRY; TYPHIMURIUM;
PREVALENCE; AMPHIBIANS; EXPOSURE; SURVIVAL; REPTILES; CONTACT
AB While most human Salmonella infections result from exposure to contaminated foods, an estimated 11% of all Salmonella infections are attributed to animal exposures, including both direct animal handling and indirect exposures such as cleaning cages and handling contaminated pet food. This report describes the epidemiologic, environmental and laboratory investigations conducted in the United States as part of the response to an international outbreak of tetracycline-resistant Salmonella enterica serotype I 4,[5],12:i:- infections with over 500 illnesses occurring from 2008 to 2010. This investigation found that illness due to the outbreak strain was significantly associated with exposure to pet reptiles and frozen feeder rodents used as food for pet reptiles. Salmonella isolates indistinguishable from the outbreak strain were isolated from a frozen feeder mice-fed reptile owned by a case patient, as well as from frozen feeder mice and environmental samples collected from a rodent producing facility (Company A). An international voluntary recall of all Company A produced frozen feeder animals sold between May 2009 and July 2010 occurred. Only 13% of cases in our investigation were aware of the association between Salmonella infection and mice or rats. Consumers, the pet industry, healthcare providers and veterinarians need to be aware of the potential health risk posed by feeder rodents, whether live or frozen. Frozen feeder rodent producers, suppliers and distributors should follow the animal food labelling requirements as described in 21 CFR 501.5, and all packages of frozen feeder rodents should include safe handling instructions. Persons should wash their hands thoroughly with soap and water after handling live or frozen feeder rodents, as well as reptiles or anything in the area where the animals live. Continued opportunities exist for public health officials, the pet industry, veterinarians and consumers to work together to prevent salmonellosis associated with pet food, pets and other animals.
C1 [Cartwright, E. J.] CDC, Epidem Intelligence Serv, Sci Educ & Profess Dev Program Off, OSELS, Atlanta, GA 30333 USA.
[Cartwright, E. J.; Nguyen, T.; Ayers, T.; Quammen, J.; Yendell, S. J.; Mitchell, J.; Rickert, R.; Williams, I. T.; Behravesh, C. Barton; Wright, J.] Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Natl Ctr Emerging Zoonot & Infect Dis, Atlanta, GA USA.
[Cartwright, E. J.] Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA USA.
[Melluso, C.; Hodges, A.; Li, X.] US FDA, Ctr Vet Med, Rockville, MD 20857 USA.
[Lane, C.] Publ Hlth England, Ctr Infect Dis Surveillance & Control, London, United Kingdom.
[Yendell, S. J.] CDC, Epidemiol Elect Program, Sci Educ & Profess Dev Program Off, OSELS, Atlanta, GA 30333 USA.
[Adams, J.] Assoc Publ Hlth Labs, Silver Spring, MD USA.
[Klos, R.] Wisconsin Div Publ Hlth, Madison, WI USA.
RP Cartwright, EJ (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd NE,MS A-38, Atlanta, GA 30333 USA.
EM ecartw2@emory.edu
OI Ayers, Tracy/0000-0003-4140-3263
FU United States Centers for Disease Control and Prevention
FX This work was supported by the United States Centers for Disease Control
and Prevention.
NR 40
TC 0
Z9 0
U1 3
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1863-1959
EI 1863-2378
J9 ZOONOSES PUBLIC HLTH
JI Zoonoses Public Health
PD FEB
PY 2016
VL 63
IS 1
BP 62
EP 71
DI 10.1111/zph.12205
PG 10
WC Public, Environmental & Occupational Health; Infectious Diseases;
Veterinary Sciences
SC Public, Environmental & Occupational Health; Infectious Diseases;
Veterinary Sciences
GA DB8YH
UT WOS:000368802600007
PM 25996458
ER
PT J
AU Ahn, M
Li, L
Kim, M
AF Ahn, M.
Li, L.
Kim, M.
TI THE SURVEY OF FDA APPROVED NEW MOLECULAR ENTITIES THAT ARE TERATOGENIC
AND THEIR DRUG INTERACTION POTENTIALS WITH HORMONAL CONTRACEPTIVES.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Ahn, M.; Li, L.; Kim, M.] US FDA, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PII-085
BP S98
EP S98
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600350
ER
PT J
AU Babiskin, A
Fang, L
Choi, S
Zhao, L
AF Babiskin, A.
Fang, L.
Choi, S.
Zhao, L.
TI PHARMACOKINETIC MODELING AND SIMULATION OF NALTREXONE FOR
EXTENDED-RELEASE INTRAMUSCULAR INJECTABLE SUSPENSION TO DERIVE
ALTERNATIVE BIOEQUIVALENCE METRICS.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Babiskin, A.; Fang, L.; Choi, S.; Zhao, L.] US FDA, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PI-096
BP S56
EP S56
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600199
ER
PT J
AU Dong, Z
Yang, X
Arya, V
Zhang, L
AF Dong, Z.
Yang, X.
Arya, V.
Zhang, L.
TI COMPARING VARIOUS IN VITRO PREDICTION CRITERIA TO ASSESS THE POTENTIAL
OF A NEW MOLECULAR ENTITY (NME) TO INHIBIT OCT2 AND MATE TRANSPORTERS IN
VIVO.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Dong, Z.; Yang, X.; Arya, V.; Zhang, L.] US FDA, Off Clin Pharmacol, Off Translat Sci, CDER, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PII-076
BP S94
EP S96
PG 3
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600341
ER
PT J
AU Dong, Z
Yang, X
Arya, V
Zhang, L
AF Dong, Z.
Yang, X.
Arya, V.
Zhang, L.
TI COMPARING VARIOUS IN VITRO PREDICTION CRITERIA TO ASSESS THE POTENTIAL
OF A NEW MOLECULAR ENTITY (NME) TO INHIBIT ORGANIC ANION TRANSPORTER 1
AND 3 (OAT1 AND OAT3) IN VIVO.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Dong, Z.; Yang, X.; Arya, V.; Zhang, L.] US FDA, Off Clin Pharmacol, Off Translat Sci, CDER, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PII-075
BP S94
EP S94
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600340
ER
PT J
AU Gopalakrishnan, M
Mehta, M
Uppoor, R
Mathis, M
Farchione, T
Kempf, L
Zhang, J
Younis, I
AF Gopalakrishnan, M.
Mehta, M.
Uppoor, R.
Mathis, M.
Farchione, T.
Kempf, L.
Zhang, J.
Younis, I.
TI INCREASING PLACEBO RESPONSE AND DECREASING TREATMENT EFFECTS IN
SCHIZOPHRENIA TRIALS - THE TREND CONTINUES: AN UPDATE FROM US FOOD AND
DRUG ADMINISTRATION.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Gopalakrishnan, M.; Mehta, M.; Uppoor, R.; Mathis, M.; Farchione, T.; Kempf, L.; Zhang, J.; Younis, I.] US FDA, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PII-107
BP S103
EP S103
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600371
ER
PT J
AU Grimstein, M
Hsu, V
Zhao, P
AF Grimstein, M.
Hsu, V.
Zhao, P.
TI PBPK MODELING OF CIPROFLOXACIN - KNOWLEDGE EXTENSION BY CONFIRMING THE
EFFECT OF INTRINSIC AND EXTRINSIC PATIENT FACTORS ON RENAL OAT
ACTIVITIES
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Grimstein, M.; Hsu, V.; Zhao, P.] US FDA, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PI-101
BP S57
EP S57
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600204
ER
PT J
AU Hsu, V
Grimstein, M
Zhao, P
AF Hsu, V.
Grimstein, M.
Zhao, P.
TI LEVERAGING POTENTIAL CHANGES IN RENAL TRANSPORTER ACTIVITY TO PREDICT
DRUG PHARMACOKINETICS DURING PREGNANCY USING PBPK MODELING
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Hsu, V.; Grimstein, M.; Zhao, P.] US FDA, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PI-100
BP S57
EP S57
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600203
ER
PT J
AU Hsueh, C
Yoshida, K
Meyer, T
Zhang, L
Huang, S
Giacomini, K
AF Hsueh, C.
Yoshida, K.
Meyer, T.
Zhang, L.
Huang, S.
Giacomini, K.
TI THE ACTIVITIES OF ORGANIC ANION TRANSPORTERS, OATP1B1/1B3 AND OAT1/3 ARE
MODULATED BY UREMIC TOXINS.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Hsueh, C.; Giacomini, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Yoshida, K.; Zhang, L.; Huang, S.] US FDA, Silver Spring, MD USA.
[Meyer, T.] Stanford Univ, Stanford, CA 94305 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PWII-1
BP S73
EP S73
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600259
ER
PT J
AU Hsueh, C
Yoshida, K
Meyer, T
Zhang, L
Huang, S
Giacomini, K
AF Hsueh, C.
Yoshida, K.
Meyer, T.
Zhang, L.
Huang, S.
Giacomini, K.
TI THE ACTIVITIES OF ORGANIC ANION TRANSPORTERS, OATP1B1/1B3 AND OAT1/3
AREMODULATED BY UREMIC TOXINS. C.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Hsueh, C.; Giacomini, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Yoshida, K.; Zhang, L.; Huang, S.] US FDA, Silver Spring, MD USA.
[Meyer, T.] Stanford Univ, Stanford, CA 94305 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PT-08
BP S15
EP S15
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600040
ER
PT J
AU Lee, J
Wang, J
Florian, J
Wang, Y
Kettl, D
Marcus, K
Woitach, A
AF Lee, J.
Wang, J.
Florian, J.
Wang, Y.
Kettl, D.
Marcus, K.
Woitach, A.
TI EXPOSURE-RESPONSE ANALYSES IN THE RISK-BENEFIT EVALUATION OF SECUKINUMAB
FOR PLAQUE PSORIASIS.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Lee, J.; Wang, J.; Florian, J.; Wang, Y.; Kettl, D.; Marcus, K.; Woitach, A.] US FDA, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PI-140
BP S67
EP S68
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600243
ER
PT J
AU Liu, J
Kim, G
Xu, J
McKee, A
Hu, M
Palmby, T
Zhuang, L
Zhao, L
AF Liu, J.
Kim, G.
Xu, J.
McKee, A.
Hu, M.
Palmby, T.
Zhuang, L.
Zhao, L.
TI COMBINED POPULATION PK MODELING AND DISPROPORTIONALITY ANALYSES TO
ASSESS THE ASSOCIATION BETWEEN KINASE INHIBITION AND ADVERSE EVENTS.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Liu, J.] Indiana Univ Sch Med, Dept Med, Div Clin Pharmacol, Indianapolis, IN 46202 USA.
[Kim, G.; Xu, J.; McKee, A.; Palmby, T.] US FDA, Off Hematol & Oncol Prod, Off New Drugs, CDER, Silver Spring, MD USA.
[Hu, M.; Zhao, L.] US FDA, Div Quantitat Methods & Modeling, Off Res & Stand, Off Gener Drugs,CDER, Silver Spring, MD USA.
[Zhuang, L.] US FDA, Div Pharmacometr, Off Clin Pharmacol, Off Translat Sci,CDER, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PII-044
BP S86
EP S86
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600309
ER
PT J
AU Liu, J
Kim, G
Xu, J
McKee, A
Hu, M
Palmby, T
Zhuang, L
Zhao, L
AF Liu, J.
Kim, G.
Xu, J.
McKee, A.
Hu, M.
Palmby, T.
Zhuang, L.
Zhao, L.
TI COMBINED POPULATION PK MODELING AND DISPROPORTIONALITY ANALYSES TO
ASSESS THE ASSOCIATION BETWEEN KINASE INHIBITION AND ADVERSE EVENTS.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Liu, J.] Indiana Univ Sch Med, Dept Med, Div Clin Pharmacol, Indianapolis, IN 46202 USA.
[Kim, G.; Xu, J.; McKee, A.; Palmby, T.] US FDA, Off Hematol & Oncol Prod, Off New Drugs, CDER, Silver Spring, MD USA.
[Hu, M.; Zhao, L.] US FDA, Div Quantitat Methods & Modeling, Off Res & Stand, Off Gener Drugs,CDER, Silver Spring, MD USA.
[Zhuang, L.] US FDA, Div Pharmacometr, Off Clin Pharmacol, Off Translat Sci,CDER, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA OPC-4
BP S12
EP S13
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600032
ER
PT J
AU Ma, L
Habtemariam, B
Dinndorf, P
Mercado, MS
Lin, T
Wang, Y
AF Ma, L.
Habtemariam, B.
Dinndorf, P.
Mercado, M. S.
Lin, T.
Wang, Y.
TI OPTIMIZING THE DOSE OF PLERIXAFOR IN LOW BODY WEIGHT PATIENTS WITH
NON-HODGKIN'S LYMPHOMA.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Ma, L.; Habtemariam, B.; Dinndorf, P.; Wang, Y.] US FDA, Silver Spring, MD USA.
[Mercado, M. S.; Lin, T.] Sanofi, Cambridge, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PI-074
BP S50
EP S51
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600177
ER
PT J
AU Ma, L
Williams, GM
Ouyang, Y
Dickerson, W
Huang, L
Melhem, M
Chow, AT
Yang, B
Harrold, JM
Laniyonu, A
Zalkikar, J
Gorovets, A
Marzella, L
Mehrotra, N
AF Ma, L.
Williams, G. M.
Ouyang, Y.
Dickerson, W.
Huang, L.
Melhem, M.
Chow, A. T.
Yang, B.
Harrold, J. M.
Laniyonu, A.
Zalkikar, J.
Gorovets, A.
Marzella, L.
Mehrotra, N.
TI PATIENTS WITH HEMATOPOIETIC SYNDROME OF ACUTE RADIATION SYNDROME
(HS-ARS): CONSIDERATIONS ON THE DOSE SELECTION FOR FILGRASTIM UNDER THE
ANIMAL RULE.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Ma, L.; Williams, G. M.; Ouyang, Y.; Dickerson, W.; Huang, L.; Laniyonu, A.; Zalkikar, J.; Gorovets, A.; Marzella, L.; Mehrotra, N.] US FDA, Silver Spring, MD USA.
[Melhem, M.; Chow, A. T.; Yang, B.; Harrold, J. M.] Amgen Inc, Thousand Oaks, CA 91320 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PI-073
BP S50
EP S50
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600176
ER
PT J
AU Madrasi, K
Samant, S
Kim, M
Li, F
Voss, S
Kehoe, T
Schmidt, S
Li, L
AF Madrasi, K.
Samant, S.
Kim, M.
Li, F.
Voss, S.
Kehoe, T.
Schmidt, S.
Li, L.
TI DEVELOPMENT OF A MECHANISM-BASED DRUG-DISEASE MODEL TO QUANTIFY
POSTMENOPAUSAL OSTEOPOROSIS.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Madrasi, K.; Kim, M.; Li, F.; Voss, S.; Kehoe, T.; Li, L.] US FDA, Silver Spring, MD USA.
[Samant, S.; Schmidt, S.] Univ Florida, Orlando, FL USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA OII-2
BP S105
EP S105
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600378
ER
PT J
AU Meng, Z
Trame, MN
Schmidt, S
Fang, L
Lesko, L
AF Meng, Z.
Trame, M. N.
Schmidt, S.
Fang, L.
Lesko, L.
TI APPLICATION OF PHARMACOKINETIC/PHARMACODYNAMIC MODELING TO SIMULATE
POTENTIAL DIFFERENCES IN BIOEQUIVALENCE BETWEEN GENERIC AND BRAND NAME
GABAPENTIN PRODUCTS
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Meng, Z.; Trame, M. N.; Schmidt, S.; Lesko, L.] Univ Florida, Orlando, FL USA.
[Fang, L.] US FDA, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PI-117
BP S61
EP S62
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600220
ER
PT J
AU Mizuno, T
Fukuda, T
Emoto, C
Christians, U
Jiang, W
Alloway, RR
Vinks, AA
AF Mizuno, T.
Fukuda, T.
Emoto, C.
Christians, U.
Jiang, W.
Alloway, R. R.
Vinks, A. A.
TI POPULATION PHARMACOKINETIC-PHARMACOGENETIC ANALYSIS OF TACROLIMUS IN
RENAL TRANSPLANT PATIENTS PARTICIPATING IN A PROSPECTIVE BIOEQUIVALENCE
STUDY.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Mizuno, T.; Fukuda, T.; Emoto, C.; Vinks, A. A.] Cincinnati Childrens Hosp Med Ctr, Div Clin Pharmacol, Cincinnati, OH 45229 USA.
[Christians, U.] Univ Colorado, Clin Res & Dev iC42, Aurora, CO USA.
[Jiang, W.] US FDA, Off Gener Drugs, Silver Spring, MD USA.
[Alloway, R. R.] Univ Cincinnati, Coll Med, Dept Internal Med, Div Nephrol, Cincinnati, OH USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PI-039
BP S41
EP S41
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600142
ER
PT J
AU Pan, Y
Cui, M
Jiang, X
Conner, D
Zhao, L
Stier, E
AF Pan, Y.
Cui, M.
Jiang, X.
Conner, D.
Zhao, L.
Stier, E.
TI PBPK MODELING AND SIMULATION OF RECTAL/COLON ABSORPTION FOR SUPPOSITORY
DRUGS.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Pan, Y.; Cui, M.; Jiang, X.; Conner, D.; Zhao, L.; Stier, E.] US FDA, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PI-038
BP S41
EP S41
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600141
ER
PT J
AU Ramamoorthy, A
Sadler, BM
van Hasselt, J
Elassaiss-Schaap, J
Kasichayanula, S
Edwards, Y
van der Graaf, PH
Zhang, L
Wagner, JA
AF Ramamoorthy, A.
Sadler, B. M.
van Hasselt, J.
Elassaiss-Schaap, Jeroen
Kasichayanula, S.
Edwards, Y.
van der Graaf, P. H.
Zhang, L.
Wagner, J. A.
TI THE PROOF IS IN THE PEE: WHAT HAVE WE LEARNED ABOUT POPULATION ASPARAGUS
URINARY ODOR KINETICS?
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Ramamoorthy, A.; Zhang, L.] US FDA, Silver Spring, MD USA.
[Sadler, B. M.; Edwards, Y.] ICON, Raleigh, NC USA.
[van Hasselt, J.; Elassaiss-Schaap, Jeroen; van der Graaf, P. H.] Leiden Univ, Leiden, Netherlands.
[Kasichayanula, S.] Amgen Inc, Thousand Oaks, CA 91320 USA.
[Wagner, J. A.] Takeda Pharmaceut Int Co, Cambridge, MA USA.
RI Elassaiss-Schaap , Jeroen/Q-5451-2016
NR 0
TC 0
Z9 0
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PI-083
BP S53
EP S53
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600186
ER
PT J
AU Wagner, C
Pan, Y
Hsu, V
Sinha, V
Zhao, P
AF Wagner, C.
Pan, Y.
Hsu, V.
Sinha, V.
Zhao, P.
TI PREDICTING THE EFFECT OF CYP3A INDUCERS ON THE PHARMACOKINETICS OF
SUBSTRATE DRUGS USING PBPK MODELING - AN ANALYSIS OF PBPK SUBMISSIONS TO
THE FDA
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Wagner, C.; Pan, Y.; Hsu, V.; Sinha, V.; Zhao, P.] US FDA, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA E-022
BP S26
EP S27
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600084
ER
PT J
AU Yoshida, K
Sun, B
Zhao, P
Zhang, L
Huang, S
AF Yoshida, K.
Sun, B.
Zhao, P.
Zhang, L.
Huang, S.
TI COMPARISON OF THE EFFECT OF CHRONIC KIDNEY DISEASE (CKD) ON
PHARMACOKINETICS OF OATP, CYP2D6, AND CYP3A SUBSTRATES.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Yoshida, K.; Sun, B.; Zhao, P.; Zhang, L.; Huang, S.] US FDA, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PII-004
BP S76
EP S76
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600271
ER
PT J
AU Younis, IR
Sinha, V
AF Younis, I. R.
Sinha, V.
TI THE ROLE OF POPULATION PK IN INFORMING DOSING RECOMMENDATIONS FOR
PATIENTS WITH HEPATIC AND RENAL IMPAIRMENT.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Younis, I. R.; Sinha, V.] US FDA, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PII-106
BP S103
EP S103
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600370
ER
PT J
AU Zaman, S
Gao, C
Abernethy, DR
AF Zaman, S.
Gao, C.
Abernethy, D. R.
TI A SYSTEMS BIOLOGY APPROACH TO PREDICTING CARDIOTOXICITY ASSOCIATED WITH
TYROSINE KINASE INHIBITORS.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Zaman, S.; Abernethy, D. R.] US FDA, Silver Spring, MD USA.
[Gao, C.] Rutgers State Univ, New Brunswick, NJ 08903 USA.
NR 0
TC 0
Z9 0
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PWIII-4
BP S75
EP S75
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600266
ER
PT J
AU Zaman, S
Gao, C
Abernethy, DR
AF Zaman, S.
Gao, C.
Abernethy, D. R.
TI A SYSTEMS BIOLOGY APPROACH TO PREDICTING CARDIOTOXICITY ASSOCIATED WITH
TYROSINE KINASE INHIBITORS.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Zaman, S.; Abernethy, D. R.] US FDA, Silver Spring, MD USA.
[Gao, C.] Rutgers State Univ, New Brunswick, NJ 08903 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PT-29
BP S20
EP S20
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600061
ER
PT J
AU Zaman, S
Gao, C
Abernethy, DR
AF Zaman, S.
Gao, C.
Abernethy, D. R.
TI A SYSTEMS BIOLOGY APPROACH TO PREDICTING CARDIOTOXICITY ASSOCIATED WITH
TYROSINE KINASE INHIBITORS.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Zaman, S.; Abernethy, D. R.] US FDA, Silver Spring, MD USA.
[Gao, C.] Rutgers State Univ, New Brunswick, NJ 08903 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PC-12
BP S7
EP S8
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600013
ER
PT J
AU Zhang, N
Shon, J
Kim, M
Li, L
AF Zhang, N.
Shon, J.
Kim, M.
Li, L.
TI ROLE OF CYP3A4 IN ORAL CONTRACEPTIVE CLEARANCE.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Zhang, N.; Shon, J.; Kim, M.; Li, L.] US FDA, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PI-095
BP S56
EP S56
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600198
ER
PT J
AU Zhou, T
Arya, V
Zhang, L
AF Zhou, T.
Arya, V.
Zhang, L.
TI COMPARING VARIOUS IN VITRO PREDICTION CRITERIA TO ASSESS THE POTENTIAL
OF A NEW MOLECULAR ENTITY (NME) TO INHIBIT P-GLYCOPROTEIN (P-GP) IN
VIVO.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Zhou, T.; Arya, V.; Zhang, L.] US FDA, Off Clin Pharmacol, Off Translat Sci, CDER, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PII-057
BP S89
EP S90
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600322
ER
PT J
AU Zhuang, L
Wang, X
Ma, L
Bhattaram, A
Mulugeta, Y
Yu, J
Mehrotra, N
Wang, Y
AF Zhuang, L.
Wang, X.
Ma, L.
Bhattaram, A.
Mulugeta, Y.
Yu, J.
Mehrotra, N.
Wang, Y.
TI APPLICATION OF PHARMACOMETRICS IN DOSE SELECTION OF DRUGS AND BIOLOGICS
DEVELOPED UNDER THE ANIMAL RULE. L.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 08-12, 2016
CL San Diego, CA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Zhuang, L.; Wang, X.; Ma, L.; Bhattaram, A.; Mulugeta, Y.; Yu, J.; Mehrotra, N.; Wang, Y.] US FDA, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2016
VL 99
SU 1
MA PI-048
BP S43
EP S43
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB7JZ
UT WOS:000368692600151
ER
PT J
AU Segars, K
Simpson, S
Kerdahi, K
Sulaiman, IM
AF Segars, Katharine
Simpson, Steven
Kerdahi, Khalil
Sulaiman, Irshad M.
TI Evaluation of Cronobacter Growth and Phenotypic Variation Under Modified
Culture Conditions
SO CURRENT MICROBIOLOGY
LA English
DT Article
ID ENTEROBACTER-SAKAZAKII; INFANT FORMULA; PRODUCTS; MEDIA; MILK
AB Cronobacter sakazakii is an opportunistic pathogen known to cause acute meningitis and necrotizing enterocolitis in neonates and immunocompromised individuals. It has been isolated from a wide range of food and environmental samples, and has been linked to outbreaks associated with powdered infant formula. This study was carried out to assess variations in growth conditions (temperature, pH, and sugar supplement) and to establish how these changes impact phenotypic characteristics for successful recovery and identification of Cronobacter, particularly for routine surveillance purposes. A total of six Cronobacter isolates were tested to evaluate the above growth conditions, including three ATCC Cronobacter reference and three environmental isolates obtained from regulatory sample screening. Although only slight changes in colony-forming units were observed across the pH range and the sugars tested, the morphology was significantly impacted by changes in these growth factors. Incubation between 30 and 50 A degrees C resulted in growth after 24 h, and the growth was slower at ambient temperature and colony formation was most robust at 30 A degrees C. Results of this study suggest that 30 A degrees C may be suitable for recovery of some Cronobacter strains, and minor variations in growth conditions can alter colony morphology and appearance. Expression of unique biological characteristics based on phenotypic observations may be beneficial for differentiating various Cronobacter strains.
C1 [Segars, Katharine; Simpson, Steven; Kerdahi, Khalil; Sulaiman, Irshad M.] US FDA, Southeast Reg Lab, 60 Eighth St, Atlanta, GA 30309 USA.
RP Sulaiman, IM (reprint author), US FDA, Southeast Reg Lab, 60 Eighth St, Atlanta, GA 30309 USA.
EM Irshad.Sulaiman@fda.hhs.gov
FU FDA Commissioner's Fellowship Program
FX The findings and conclusions in this manuscript are those of the authors
and do not necessarily represent the views or official position of the
U.S. Food and Drug Administration (FDA). The names of vendors or
manufacturers are provided as examples of available product sources;
inclusion does not imply endorsement of the vendors, manufacturers, or
products by the FDA or the U.S. Department of Health and Human Services.
This study was supported in part by funding from the FDA 2013
Commissioner's Fellowship Program. The funders had no role in the study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 16
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U1 1
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0343-8651
EI 1432-0991
J9 CURR MICROBIOL
JI Curr. Microbiol.
PD FEB
PY 2016
VL 72
IS 2
BP 190
EP 197
DI 10.1007/s00284-015-0936-1
PG 8
WC Microbiology
SC Microbiology
GA DB6PO
UT WOS:000368637300012
PM 26567034
ER
PT J
AU Srigley, CT
Oles, CJ
Kia, ARF
Mossoba, MM
AF Srigley, Cynthia T.
Oles, Carolyn J.
Kia, Ali Reza Fardin
Mossoba, Magdi M.
TI Authenticity Assessment of Extra Virgin Olive Oil: Evaluation of
Desmethylsterols and Triterpene Dialcohols
SO JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY
LA English
DT Article
DE Adulteration; Authenticity; Desmethylsterol; Erythrodiol; Extra virgin
olive oil; Gas chromatography; Purity; Sterol; Triterpene dialcohol;
Uvaol
ID HAZELNUT OIL; ESTERIFIED STEROLS; ADULTERATION; PHYTOSTEROLS; ALCOHOLS;
CULTIVAR; QUALITY; COLUMN; GC
AB Extra virgin olive oil (EVOO) has a long history of economic adulteration, the detection of which presents significant challenges due to the diverse composition of cultivars grown around the world and the limitations of existing methods for detecting adulteration. In this study, using Method COI/T.20/Doc. No. 30/Rev. 1 of the International Olive Council, the authenticity of 88 market samples of EVOO was evaluated by comparing total sterol contents, desmethylsterol composition, and contents of triterpene dialcohols (erythrodiol and uvaol) with purity criteria specified in the United States Standards for grades of olive oil and olive-pomace oil. Three of the 88 samples labeled as EVOO failed to meet purity criteria, indicating possible adulteration with commodity oil and/or solvent-extracted olive oil. Detection of adulteration was also evaluated by spiking an EVOO sample with commodity oil at the 10 % level. As expected, eight of the spiked samples (canola, corn, hazelnut, peanut, safflower, soybean, and sunflower oils, and palm olein) failed to meet purity criteria. Two of the three samples spiked with 10 % hazelnut oil went undetected for adulteration. Overall, a low occurrence rate of adulteration (< 5 %), based on purity criteria for desmethylsterols and triterpene dialcohols, was detected for the 88 products labeled as EVOO.
C1 [Srigley, Cynthia T.; Oles, Carolyn J.; Kia, Ali Reza Fardin; Mossoba, Magdi M.] US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
RP Srigley, CT (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM cynthia.srigley@fda.hhs.gov
NR 30
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Z9 1
U1 5
U2 21
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0003-021X
EI 1558-9331
J9 J AM OIL CHEM SOC
JI J. Am. Oil Chem. Soc.
PD FEB
PY 2016
VL 93
IS 2
BP 171
EP 181
DI 10.1007/s11746-015-2759-4
PG 11
WC Chemistry, Applied; Food Science & Technology
SC Chemistry; Food Science & Technology
GA DB7NH
UT WOS:000368701800002
ER
PT J
AU Butler, KS
Young, MYL
Li, ZH
Elespuru, RK
Wood, SC
AF Butler, Kimberly S.
Young, Megan Y. L.
Li, Zhihua
Elespuru, Rosalie K.
Wood, Steven C.
TI Performance characteristics of the AmpliSeq Cancer Hotspot panel v2 in
combination with the Ion Torrent Next Generation Sequencing Personal
Genome Machine
SO REGULATORY TOXICOLOGY AND PHARMACOLOGY
LA English
DT Article
DE Next generation sequencing; Cancer Hotspot panel; Ion Torrent Personal
Genome Machine; Mutation detection; Systematic error analysis;
Performance analysis
ID DIAGNOSTICS; GENES; MUTATIONS; PGM
AB Next-Generation Sequencing is a rapidly advancing technology that has research and clinical applications. For many cancers, it is important to know the precise mutation(s) present, as specific mutations could indicate or contra-indicate certain treatments as well as be indicative of prognosis. Using the Ion Torrent Personal Genome Machine and the AmpliSeq Cancer Hotspot panel v2, we sequenced two pancreatic cancer cell lines, BxPC-3 and HPAF-II, alone or in mixtures, to determine the error rate, sensitivity, and reproducibility of this system. The system resulted in coverage averaging 2000x across the various amplicons and was able to reliably and reproducibly identify mutations present at a rate of 5%. Identification of mutations present at a lower rate was possible by altering the parameters by which calls were made, but with an increase in erroneous, low-level calls. The panel was able to identify known mutations in these cell lines that are present in the COSMIC database. In addition, other, novel mutations were also identified that may prove clinically useful. The system was assessed for systematic errors such as homopolymer effects, end of amplicon effects and patterns in NO CALL sequence. Overall, the system is adequate at identifying the known, targeted mutations in the panel. Published by Elsevier Inc.
C1 [Butler, Kimberly S.; Young, Megan Y. L.; Elespuru, Rosalie K.; Wood, Steven C.] US FDA, Off Med Prod & Tobacco, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs,Div Biol Chem & Mat Sci, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
[Li, Zhihua] US FDA, Off Med Prod & Tobacco, Ctr Drug Evaluat & Res, Off Translat Sci,Off Clin Pharmacol,Div Appl Regu, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
RP Wood, SC (reprint author), US FDA, Off Med Prod & Tobacco, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs,Div Biol Chem & Mat Sci, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM steven.wood@fda.hhs.gov
FU Medical Countermeasures Initiative; Critical Path Program; MCMi Program;
National Cancer Institute Interagency Oncology Taskforce; Office of
Science and Engineering Laboratories, CDRH, FDA; U.S. Department of
Energy; U.S. Food and Drug Administration
FX The authors thank the Medical Countermeasures Initiative for funding
this work. The authors acknowledge E. Mansfield (CDRH/OIR) and P. Potnis
(CDRH/ODE) for securing funds from the Critical Path and MCMi Programs
to establish the Ion Torrent Gene Sequencing Core Laboratory at
CDRH/OSEL, where this research was conducted. This study was supported
by funds provided by the National Cancer Institute Interagency Oncology
Taskforce and the Office of Science and Engineering Laboratories, CDRH,
FDA. This project was supported in part by an appointment to the
Research Participation Program at the Center for Devices and
Radiological Health administered by the Oak Ridge Institute for Science
and Education through an interagency agreement between the U.S.
Department of Energy and the U.S. Food and Drug Administration.
NR 24
TC 0
Z9 0
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0273-2300
EI 1096-0295
J9 REGUL TOXICOL PHARM
JI Regul. Toxicol. Pharmacol.
PD FEB
PY 2016
VL 74
BP 178
EP 186
DI 10.1016/j.yrtph.2015.09.011
PG 9
WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology
SC Legal Medicine; Pharmacology & Pharmacy; Toxicology
GA DB5LG
UT WOS:000368555000020
PM 26387931
ER
PT J
AU Costa, AP
Xu, XM
Khan, MA
Burgess, DJ
AF Costa, Antonio P.
Xu, Xiaoming
Khan, Mansoor A.
Burgess, Diane J.
TI Liposome Formation Using a Coaxial Turbulent Jet in Co-Flow
SO PHARMACEUTICAL RESEARCH
LA English
DT Article
DE coaxial turbulent jet; continuous manufacturing; ethanol injection;
liposome processing; monodispersed liposomes; unilamellar
ID ETHANOL INJECTION METHOD; ROUND JET; NANOPARTICLES; SIZE
AB Liposomes are robust drug delivery systems that have been developed into FDA-approved drug products for several pharmaceutical indications. Direct control in producing liposomes of a particular particle size and particle size distribution is extremely important since liposome size may impact cellular uptake and biodistribution.
A device consisting of an injection-port was fabricated to form a coaxial turbulent jet in co-flow that produces liposomes via the ethanol injection method. By altering the injection-port dimensions and flow rates, a fluid flow profile (i.e., flow velocity ratio vs. Reynolds number) was plotted and associated with the polydispersity index of liposomes.
Certain flow conditions produced unilamellar, monodispersed liposomes and the mean particle size was controllable from 25 up to > 465 nm. The mean liposome size is highly dependent on the Reynolds number of the mixed ethanol/aqueous phase and independent of the flow velocity ratio.
The significance of this work is that the Reynolds number is predictive of the liposome particle size, independent of the injection-port dimensions. In addition, a new model describing liposome formation is outlined. The significance of the model is that it relates fluid dynamic properties and lipid-molecule physical properties to the final liposome size.
C1 [Costa, Antonio P.; Burgess, Diane J.] Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT 06269 USA.
[Xu, Xiaoming; Khan, Mansoor A.] FDA CDER DPQR, Silver Spring, MD 20993 USA.
RP Burgess, DJ (reprint author), Univ Connecticut, Dept Pharmaceut Sci, 69 N Eagleville Rd U3092, Storrs, CT 06269 USA.
EM d.burgess@uconn.edu
FU U.S. FDA [HHSF223201310117C]
FX This work was supported by the U.S. FDA (Grant#: HHSF223201310117C). We
thank Dr. M. Cantino and Dr. X. Sun from the Biosciences Electron
Microscope Laboratory of the Physiology and Neurobiology Department at
the University of Connecticut for their work on the negative stain TEM
micrographs. The authors would like to acknowledge Dr. Jiwen Zheng and
Dr. Yong Wu at the FDA White Oak Nanotechnology Core Facility for
instrument use, scientific and technical assistance. A. Costa was an
AFPE fellow during the time period of this research.
NR 26
TC 0
Z9 0
U1 6
U2 22
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0724-8741
EI 1573-904X
J9 PHARM RES-DORDR
JI Pharm. Res.
PD FEB
PY 2016
VL 33
IS 2
BP 404
EP 416
DI 10.1007/s11095-015-1798-8
PG 13
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA DA8RH
UT WOS:000368073300013
PM 26428671
ER
PT J
AU Kryndushkin, D
Rao, VA
AF Kryndushkin, Dmitry
Rao, V. Ashutosh
TI Comparative Effects of Metal-Catalyzed Oxidizing Systems on
Carbonylation and Integrity of Therapeutic Proteins
SO PHARMACEUTICAL RESEARCH
LA English
DT Article
DE aggregation; ascorbic acid; carbonylation; leachables; protein
pharmaceuticals
ID AMINO-ACID-RESIDUES; MONOCLONAL-ANTIBODIES; MEDIATED OXIDATION; FENTON
CHEMISTRY; ASCORBIC-ACID; FREE-RADICALS; STABILITY; FORMULATION;
BINDING; GROWTH
AB Ascorbic acid has been considered as a potential radical scavenging excipient for pharmaceutical formulations. However, under certain circumstances, ascorbic acid can generate reactive oxygen species via redox cycling. The objective of this study was to investigate ascorbic acid-induced oxidative carbonylation of therapeutic proteins and correlate the increase in carbonylation with protein aggregation.
An optimized ELISA for quantifying carbonyl levels was used to compare the oxidizing potentials of ascorbic acid and hydrogen peroxide by testing four pharmaceutically-relevant proteins (human serum albumin, immunoglobulin G, granulocyte-colony stimulating factor and calcitonin). Several transition metals at micromolar concentrations were evaluated for their ability to enhance ascorbic acid-induced protein carbonylation. Protein aggregation under oxidative conditions, with or without free radical scavengers, was measured by aggregate binding fluorescent dye and confirmed by microfluidic imaging.
Addition of ascorbic acid alone resulted in higher increases in carbonylation than addition of hydrogen peroxide. The presence of trace amounts (> 75 ppb) of copper enhanced oxidative effects of ascorbic acid, whereas other tested metals did not comparably promote oxidation. During oxidation, protein destabilization indicated by loss of the full-length protein, positively correlated with the increase in protein aggregation. However, levels of aggregation did not always correlate with the levels of protein carbonylation. At comparable carbonylation levels, addition of copper produced greater protein destabilization and aggregation than addition of iron.
The results strongly suggest that ascorbic acid with traces of metals, especially copper, can promote therapeutic protein carbonylation and potentially aggregation. At similar carbonylation levels, some oxidative conditions may lead to greater protein destabilization than others.
C1 [Kryndushkin, Dmitry; Rao, V. Ashutosh] US FDA, Lab Appl Biochem, Div Biotechnol Prod Res & Review 3, Off Biotechnol Prod,Off Pharmaceut Qual,Ctr Drug, Silver Spring, MD 20993 USA.
RP Rao, VA (reprint author), US FDA, Lab Appl Biochem, Div Biotechnol Prod Res & Review 3, Off Biotechnol Prod,Off Pharmaceut Qual,Ctr Drug, Silver Spring, MD 20993 USA.
EM ashutosh.rao@fda.hhs.gov
FU CDER Critical Path Initiative
FX This research was supported by the CDER Critical Path Initiative. We
thank Dr. Shen Luo for help with microfluidic imaging. We would like to
thank Dr. Hiroshi Uehara and Elliot Rosen (FDA) for critical reading of
the manuscript. The authors have no competing financial interests to
disclose. The views expressed in this article are those of the authors
and do not necessarily reflect the official policy or position of the
U.S. Food and Drug Administration and the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government.
NR 52
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U1 3
U2 9
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0724-8741
EI 1573-904X
J9 PHARM RES-DORDR
JI Pharm. Res.
PD FEB
PY 2016
VL 33
IS 2
BP 526
EP 539
DI 10.1007/s11095-015-1807-y
PG 14
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA DA8RH
UT WOS:000368073300022
PM 26499343
ER
PT J
AU Brink, JA
Miller, DL
AF Brink, James A.
Miller, Donald L.
TI NCRP PROGRAM AREA COMMITTEE 4: RADIATION PROTECTION IN MEDICINE
SO HEALTH PHYSICS
LA English
DT Article
DE National Council on Radiation Protection and Measurements; fluoroscopy;
radiation protection; radiation; medical
AB Program Area Committee (PAC) 4 deals with issues in radiation protection in healthcare settings. NCRP Statement No. 11 was published at the end of 2014, and three active scientific committees (SC) are at workSC 4-5, SC 4-7, and SC 4-8. PAC 4 is also considering a number of topics that could be addressed by new scientific committees in the future.
C1 [Brink, James A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Miller, Donald L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Brink, JA (reprint author), Massachusetts Gen Hosp, 175 Cambridge St,2nd Floor, Boston, MA 02114 USA.
EM jabrink@partners.org
NR 3
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD FEB
PY 2016
VL 110
IS 2
BP 106
EP 108
DI 10.1097/HP.0000000000000403
PG 3
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA DA5CC
UT WOS:000367818700005
PM 26717159
ER
PT J
AU Harris, GR
Church, CC
Dalecki, D
Ziskin, MC
Bagley, JE
AF Harris, Gerald R.
Church, Charles C.
Dalecki, Diane
Ziskin, Marvin C.
Bagley, Jennifer E.
TI COMPARISON OF THERMAL SAFETY PRACTICE GUIDELINES FOR DIAGNOSTIC
ULTRASOUND EXPOSURES
SO ULTRASOUND IN MEDICINE AND BIOLOGY
LA English
DT Review
DE Bio-effects; Fetal; Output display standard; Thermal index; Ultrasound
ID AMERICAN-INSTITUTE; INDEX; HYPERTHERMIA; PREGNANCY; DEFECTS; RAT
AB This article examines the historical evolution of various practice guidelines designed to minimize the possibility of thermal injury during a diagnostic ultrasound examination, including those published by the American Institute of Ultrasound in Medicine, British Medical Ultrasound Society and Health Canada. The guidelines for prenatal/neonatal examinations are in general agreement, but significant differences were found for postnatal exposures. We propose sets of thermal index versus exposure time for these examination categories below which there is reasonable assurance that an examination can be conducted without risk of producing an adverse thermal effect under any scanning conditions. If it is necessary to exceed these guidelines, the occurrence of an adverse thermal event is still unlikely in most situations because of mitigating factors such as transducer movement and perfusion, but the general principle of "as low as reasonably achievable'' should be followed. Some limitations of the biological effects studies underpinning the guidelines also are discussed briefly. (C) 2016 World Federation for Ultrasound in Medicine & Biology.
C1 [Harris, Gerald R.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Church, Charles C.] Univ Mississippi, Natl Ctr Phys Acoust, University, MS 38677 USA.
[Dalecki, Diane] Univ Rochester, Dept Biomed Engn, Rochester, NY USA.
[Ziskin, Marvin C.] Temple Univ, Sch Med, Ctr Biomed Phys, Philadelphia, PA 19122 USA.
[Bagley, Jennifer E.] Univ Oklahoma, Hlth Sci Ctr, Dept Med Imaging & Radiat Sci, Tulsa, OK USA.
RP Harris, GR (reprint author), 132 South Van Buren St, Rockville, MD 20850 USA.
EM gerald.harris13@gmail.com
NR 33
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Z9 1
U1 2
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-5629
EI 1879-291X
J9 ULTRASOUND MED BIOL
JI Ultrasound Med. Biol.
PD FEB
PY 2016
VL 42
IS 2
BP 345
EP 357
DI 10.1016/j.ultrasmedbio.2015.09.016
PG 13
WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
GA DA3XX
UT WOS:000367735800001
PM 26626492
ER
PT J
AU Chamkasem, N
Lee, S
Harmon, T
AF Chamkasem, Narong
Lee, Sookwang
Harmon, Tiffany
TI Analysis of 19 PCB congeners in catfish tissue using a modified QuEChERS
method with GC-MS/MS
SO FOOD CHEMISTRY
LA English
DT Article
DE Triple quadrupole; Tandem mass spectrometry; Gas chromatography; PCB
congeners residue analysis; Catfish; QuEChERS
ID CAPILLARY GAS-CHROMATOGRAPHY; POLYCHLORINATED-BIPHENYLS;
PESTICIDE-RESIDUES; EXTRACTION; PRODUCE
AB A simple approach to determine 19 PCB congeners in catfish tissue was presented. A modified QuEChERS method employing high solvent to sample ratio 10:1 was used to improve the extraction recovery of 19 PCB congeners. After salting out by shaking with anhydrous magnesium sulfate and sodium chloride, 1 mL of acetonitrile extract was pipetted into a 2-mL centrifuge tube containing anhydrous magnesium sulfate, primary secondary amine sorbent, and C-18 sorbent. The tube was then shaken and centrifuged to absorb fat and fatty acid residue present in the acetonitrile extract. The acetonitrile extract was analyzed by GC-MS/MS. The excellent sensitivity of GC-MS/MS allows for the direct injection of the samples to detect the low level of the PCB congeners. The method therefore is high throughput, uses fewer consumable lab supplies, and provides excellent sensitivity with an LOQ below 1 ng/g. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Chamkasem, Narong; Lee, Sookwang; Harmon, Tiffany] US FDA, Southeast Reg Lab, Atlanta, GA 30309 USA.
RP Chamkasem, N (reprint author), US FDA, Southeast Reg Lab, 60 Eighth St NE, Atlanta, GA 30309 USA.
EM narong.chamkasem@fda.hhs.gov
NR 16
TC 2
Z9 2
U1 8
U2 180
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0308-8146
EI 1873-7072
J9 FOOD CHEM
JI Food Chem.
PD FEB 1
PY 2016
VL 192
BP 900
EP 906
DI 10.1016/j.foodchem.2015.07.088
PG 7
WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics
SC Chemistry; Food Science & Technology; Nutrition & Dietetics
GA CS7ZC
UT WOS:000362304500115
PM 26304427
ER
PT J
AU Devadas, K
Biswas, S
Haleyurgirisetty, M
Wood, O
Ragupathy, V
Lee, S
Hewlett, I
AF Devadas, Krishnakumar
Biswas, Santanu
Haleyurgirisetty, Mohan
Wood, Owen
Ragupathy, Viswanath
Lee, Sherwin
Hewlett, Indira
TI Analysis of Host Gene Expression Profile in HIV-1 and HIV-2 Infected
T-Cells
SO PLOS ONE
LA English
DT Article
ID VIRUS TYPE-1 INFECTION; CD4+T CELLS; VIRAL LOAD; JURKAT CELLS;
IDENTIFICATION; CANCER; REPLICATION; METABOLISM; CD4(+); DIFFERENTIATION
AB HIV replication is closely regulated by a complex pathway of host factors, many of them being determinants of cell tropism and host susceptibility to HIV infection. These host factors are known to exert a positive or negative influence on the replication of the two major types of HIV, HIV-1 and HIV-2, thereby modulating virus infectivity, host response to infection and ultimately disease progression profiles characteristic of these two types. Understanding the differential regulation of host cellular factors in response to HIV-1 and HIV-2 infections will help us to understand the apparent differences in rates of disease progression and pathogenesis. This knowledge would aid in the discovery of new biomarkers that may serve as novel targets for therapy and diagnosis. The objective of this study was to determine the differential expression of host genes in response to HIV-1/HIV-2 infection. To achieve this, we analyzed the effects of HIV-1 (MN) and HIV-2 (ROD) infection on the expression of host factors in PBMC at the RNA level using the Agilent Whole Human Genome Oligo Microarray. Differentially expressed genes were identified and their biological functions determined. Host gene expression profiles were significantly changed. Gene expression profiling analysis identified a subset of differentially expressed genes in HIV-1 and HIV-2 infected cells. Genes involved in cellular metabolism, apoptosis, immune cell proliferation and activation, cytokines, chemokines, and transcription factors were differentially expressed in HIV-1 infected cells. Relatively few genes were differentially expressed in cells infected with HIV-2.
C1 [Devadas, Krishnakumar; Biswas, Santanu; Haleyurgirisetty, Mohan; Wood, Owen; Ragupathy, Viswanath; Lee, Sherwin; Hewlett, Indira] US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
RP Devadas, K; Hewlett, I (reprint author), US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM Krishnakumar.devadas@fda.hhs.gov; Indira.hewlett@fda.hhs.gov
FU Intramural CBER Modernizing Grant; Food and Drug Administration
FX This work was funded by an Intramural CBER Modernizing Grant and the
Food and Drug Administration.
NR 42
TC 1
Z9 1
U1 3
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 28
PY 2016
VL 11
IS 1
AR e0147421
DI 10.1371/journal.pone.0147421
PG 29
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC9GF
UT WOS:000369528400027
PM 26821323
ER
PT J
AU Gubrij, IB
Pangle, AK
Pang, L
Johnson, LG
AF Gubrij, Igor B.
Pangle, Amanda K.
Pang, Li
Johnson, Larry G.
TI Reversal of MicroRNA Dysregulation in an Animal Model of Pulmonary
Hypertension
SO PLOS ONE
LA English
DT Article
ID SMOOTH-MUSCLE-CELLS; ARTERIAL-HYPERTENSION; MOLECULAR PATHOGENESIS;
CHRONIC HYPOXIA; DISEASE; PROLIFERATION; MONOCROTALINE; GENE; SURVIVAL;
INHIBITION
AB Background
Animals models have played an important role in enhancing our understanding of the pathogenesis of pulmonary arterial hypertension (PAH). Dysregulation of the profile of microRNAs (miRNAs) has been demonstrated in human tissues from PAH patients and in animal models. In this study, we measured miRNA levels in the monocrotaline (MCT) rat model of PAH and examined whether blocking a specific dysregulated miRNA not previously reported in this model, attenuated PAH. We also evaluated changes in miRNA expression in lung specimens from MCT PAH rats overexpressing human prostacyclin synthase, which has been shown to attenuate MCT PAH.
Methods
Expression levels of a panel of miRNAs were measured in MCT-PAH rats as compared to naive (saline) control rats. Subsequently, MCT PAH rats were injected with a specific inhibitor (antagomiR) for miR-223 (A223) or a nonspecific control oligonucleotide (A-control) 4 days after MCT administration, then weekly. Three weeks later, RV systolic pressure and RV mass were measured. Total RNA, isolated from the lungs, microdissected pulmonary arteries, and right ventricle, was reverse transcribed and real-time quantitative PCR was performed. MiRNA levels were also measured in RNA isolated from paraffin sections of MCT-PAH rats overexpressing prostacyclin synthase.
Results
MiRs 17, 21, and 223 were consistently upregulated, whereas miRs 126, 145, 150, 204, 424, and 503 were downregulated in MCT PAH as compared to vehicle control. A223 significantly reduced levels of miR-223 in PA and lungs of MCT PAH rats as compared to levels measured in A-control or control MCT PAH rats, but A223 did not attenuate MCT PAH. Right ventricular mass and right ventricular systolic pressure in rats treated with A223 were not different from values in A-control or MCT PAH rats. In contrast, analysis of total RNA from lung specimens of MCT PAH rats overexpressing human prostacyclin synthase (hPGIS) demonstrated reversal of MCT-induced upregulation of miRs 17, 21, and 223 and an increase in levels of miR-424 and miR-503. Reduction in bone morphogenetic receptor 2 (BMPR2) messenger (m) RNA expression was not altered by A223, whereas human prostacyclin synthase overexpression restored BMPR2 mRNA to levels in MCT PAH to levels measured in naive controls.
Conclusions
Inhibition of miR-223 did not attenuate MCT PAH, whereas human prostacyclin synthase overexpression restored miRNA levels in MCT PAH to levels detected in naive rats. These data may establish a paradigm linking attenuation of PAH to restoration of BMPR2 signaling.
C1 [Gubrij, Igor B.; Pangle, Amanda K.; Johnson, Larry G.] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA.
[Gubrij, Igor B.; Pangle, Amanda K.; Johnson, Larry G.] Univ Arkansas Med Sci, Dept Internal Med, Div Pulm & Crit Med, Little Rock, AR 72205 USA.
[Pang, Li] Univ Arkansas Med Sci, Dept Pharmacol, Little Rock, AR 72205 USA.
[Pang, Li] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
RP Johnson, LG (reprint author), Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA.; Johnson, LG (reprint author), Univ Arkansas Med Sci, Dept Internal Med, Div Pulm & Crit Med, Little Rock, AR 72205 USA.
EM lgjohnson@uams.edu
FU U.S. Dept. of Veterans Affairs; Arkansas Biosciences Institute; Canadian
Heart Centre and Actelion Pharmaceuticals
FX This manuscript was supported by a VA Merit Grant (LGJ) from the U.S.
Dept. of Veterans Affairs and a grant from the Arkansas Biosciences
Institute (LGJ). LGJ is an investigator on the PAHQueri trial sponsored
by the Canadian Heart Centre and Actelion Pharmaceuticals. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 49
TC 0
Z9 0
U1 2
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 27
PY 2016
VL 11
IS 1
AR e0147827
DI 10.1371/journal.pone.0147827
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC9GD
UT WOS:000369528200057
PM 26815432
ER
PT J
AU Srivastava, HK
Wolfgang, S
Rodriguez, JD
AF Srivastava, Hirsch K.
Wolfgang, Steven
Rodriguez, Jason D.
TI Rapid screening of guar gum using portable Raman spectral identification
methods
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE Rapid screening; Economically-motivated adulteration; Raw ingredients;
Spectroscopy; Identification tests
ID SPECTROSCOPY
AB Guar gum is a well-known inactive ingredient (excipient) used in a variety of oral pharmaceutical dosage forms as a thickener and stabilizer of suspensions and as a binder of powders. It is also widely used as a food ingredient in which case alternatives with similar properties, including chemically similar gums, are readily available. Recent supply shortages and price fluctuations have caused guar gum to come under increasing scrutiny for possible adulteration by substitution of cheaper alternatives. One way that the U.S. FDA is attempting to screen pharmaceutical ingredients at risk for adulteration or substitution is through field-deployable spectroscopic screening. Here we report a comprehensive approach to evaluate two field-deployable Raman methods-spectral correlation and principal component analysis-to differentiate guar gum from other gums. We report a comparison of the sensitivity of the spectroscopic screening methods with current compendial identification tests. The ability of the spectroscopic methods to perform unambiguous identification of guar gum compared to other gums makes them an enhanced surveillance alternative to the current compendial identification tests, which are largely subjective in nature. Our findings indicate that Raman spectral identification methods perform better than compendial identification methods and are able to distinguish guar gum from other gums with 100% accuracy for samples tested by spectral correlation and principal component analysis. Published by Elsevier B.V.
C1 [Srivastava, Hirsch K.; Wolfgang, Steven; Rodriguez, Jason D.] US FDA, Div Pharmaceut Anal, Ctr Drug Evaluat & Res, St Louis, MO 63110 USA.
RP Rodriguez, JD (reprint author), US FDA, Div Pharmaceut Anal, Ctr Drug Evaluat & Res, 645 S Newstead Ave, St Louis, MO 63110 USA.
EM Jason.Rodriguez@fda.hhs.gov
OI Rodriguez, Jason/0000-0002-8814-1144; Wolfgang,
Steven/0000-0001-6512-3210
FU CDER Critical Path and Regulatory Science & Review Enhancement Programs
FX This project was supported in part by the CDER Critical Path and
Regulatory Science & Review Enhancement Programs. This project was
supported in part by an appointment (H.K.S) to the Research
Participation Program at the Center for Drug Evaluation and Research
administered by the Oak Ridge Institute for Science and Education
through an interagency agreement between the U.S. Department of Energy
and the U.S. Food and Drug Administration.
NR 22
TC 0
Z9 0
U1 4
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
EI 1873-264X
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD JAN 25
PY 2016
VL 118
BP 387
EP 392
DI 10.1016/j.jpba.2015.11.013
PG 6
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA DA2NT
UT WOS:000367633800046
PM 26609678
ER
PT J
AU Laux, P
Tralau, T
Tentschert, J
Blume, A
Al Dahouk, S
Baumler, W
Bernstein, E
Bocca, B
Alimonti, A
Colebrook, H
de Cuyper, C
Dahne, L
Hauri, U
Howard, PC
Janssen, P
Katz, L
Klitzman, B
Kluger, N
Krutak, L
Platzek, T
Scott-Lang, V
Serup, J
Teubner, W
Schreiver, I
Wilkniss, E
Luch, A
AF Laux, Peter
Tralau, Tewes
Tentschert, Jutta
Blume, Annegret
Al Dahouk, Sascha
Baeumler, Wolfgang
Bernstein, Eric
Bocca, Beatrice
Alimonti, Alessandro
Colebrook, Helen
de Cuyper, Christa
Daehne, Lars
Hauri, Urs
Howard, Paul C.
Janssen, Paul
Katz, Linda
Klitzman, Bruce
Kluger, Nicolas
Krutak, Lars
Platzek, Thomas
Scott-Lang, Victoria
Serup, Jorgen
Teubner, Wera
Schreiver, Ines
Wilkniss, Elena
Luch, Andreas
TI A medical-toxicological view of tattooing
SO LANCET
LA English
DT Review
ID RED TATTOO; SKIN INFECTIONS; PATCH-TEST; 1064 NM; LASER; INKS; PIGMENTS;
REMOVAL; BLACK; MICE
AB Long perceived as a form of exotic self-expression in some social fringe groups, tattoos have left their maverick image behind and become mainstream, particularly for young people. Historically, tattoo-related health and safety regulations have focused on rules of hygiene and prevention of infections. Meanwhile, the increasing popularity of tattooing has led to the development of many new colours, allowing tattoos to be more spectacular than ever before. However, little is known about the toxicological risks of the ingredients used. For risk assessment, safe intradermal application of these pigments needs data for toxicity and biokinetics and increased knowledge about the removal of tattoos. Other concerns are the potential for phototoxicity, substance migration, and the possible metabolic conversion of tattoo ink ingredients into toxic substances. Similar considerations apply to cleavage products that are formed during laser-assisted tattoo removal. In this Review, we summarise the issues of concern, putting them into context, and provide perspectives for the assessment of the acute and chronic health effects associated with tattooing.
C1 [Laux, Peter; Tralau, Tewes; Tentschert, Jutta; Blume, Annegret; Al Dahouk, Sascha; Platzek, Thomas; Schreiver, Ines; Wilkniss, Elena; Luch, Andreas] German Fed Inst Risk Assessment BfR, Dept Prod Safety, Berlin, Germany.
[Baeumler, Wolfgang] Univ Regensburg, Klin & Poliklin Dermatol, D-93053 Regensburg, Germany.
[Bernstein, Eric] Main Line Ctr Laser Surg, Ardmore, PA USA.
[Bocca, Beatrice; Alimonti, Alessandro] Ist Super Sanita, I-00161 Rome, Italy.
[Colebrook, Helen] Minist Hlth New Zealand, Wellington, New Zealand.
[de Cuyper, Christa] Acad Hosp St Jan, Brugge, Belgium.
[Daehne, Lars] Surflay Nanotec, Berlin, Germany.
[Hauri, Urs] Kantonales Lab Basel Stadt, Basel, Switzerland.
[Howard, Paul C.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Janssen, Paul] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands.
[Katz, Linda] US FDA, College Pk, MD USA.
[Klitzman, Bruce] Duke Univ, Med Ctr, Durham, NC USA.
[Kluger, Nicolas] Univ Helsinki, Helsinki, Finland.
[Kluger, Nicolas] Helsinki Univ Hosp, Helsinki, Finland.
[Krutak, Lars] Smithsonian Inst, Washington, DC 20560 USA.
[Scott-Lang, Victoria] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland.
[Serup, Jorgen] Bispebjerg Hosp, Dept Dermatol, Tattoo Clin, DK-2400 Copenhagen NV, Denmark.
[Teubner, Wera] BASF Schweiz AG, Basel, Switzerland.
RP Luch, A (reprint author), German Fed Inst Risk Assessment BfR, Dept Prod Safety, Berlin, Germany.
EM andreas.luch@bfr.bund.de
OI Al Dahouk, Sascha/0000-0003-3835-0818
FU BfR
FX The writing of this Review and the realisation of the 1st International
Conference on Tattoo Safety at the German Federal Institute for Risk
Assessment (BfR) in 2013 has been financially supported by intramural
grants of the BfR. This document does not reflect the official policy of
the USA Food and Drug Administration and the mention of specific
products does not constitute an endorsement.
NR 86
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Z9 10
U1 13
U2 28
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD JAN 23
PY 2016
VL 387
IS 10016
BP 395
EP 402
DI 10.1016/S0140-6736(15)60215-X
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA DB4XI
UT WOS:000368516500038
PM 26211826
ER
PT J
AU Agol, V
Cello, J
Chumakov, K
Ehrenfeld, E
Wimmer, E
AF Agol, Vadim
Cello, Jeronimo
Chumakov, Konstantin
Ehrenfeld, Ellie
Wimmer, Eckard
TI Eradicating polio: A balancing act
SO SCIENCE
LA English
DT Letter
C1 [Agol, Vadim; Chumakov, Konstantin] MP Chumakov Inst Poliomyelitis & Viral Encephalit, Moscow 142782, Russia.
[Agol, Vadim] Moscow MV Lomonosov State Univ, AN Belozersky Inst Physical Chem Biol, Moscow 119899, Russia.
[Cello, Jeronimo; Wimmer, Eckard] SUNY Stony Brook, Dept Mol Genet & Microbiol, Sch Med, Stony Brook, NY 11794 USA.
[Chumakov, Konstantin] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD 20903 USA.
[Ehrenfeld, Ellie] NIAID, NIH, Bethesda, MD 20892 USA.
RP Chumakov, K (reprint author), US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD 20903 USA.
EM Konstantin.Chumakov@fda.hhs.gov
NR 4
TC 0
Z9 0
U1 2
U2 9
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD JAN 22
PY 2016
VL 351
IS 6271
BP 348
EP 348
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB3VH
UT WOS:000368440500028
PM 26798005
ER
PT J
AU Min, KW
Liggett, JL
Silva, G
Wu, WW
Wang, R
Shen, RF
Eling, TE
Baek, SJ
AF Min, K-W
Liggett, J. L.
Silva, G.
Wu, W. W.
Wang, R.
Shen, R-F
Eling, T. E.
Baek, S. J.
TI NAG-1/GDF15 accumulates in the nucleus and modulates transcriptional
regulation of the Smad pathway
SO ONCOGENE
LA English
DT Article
ID DRUG-ACTIVATED GENE-1; BETA SUPERFAMILY MEMBER; GROWTH-FACTOR-BETA;
COLORECTAL-CANCER CELLS; MORPHOGENETIC PROTEIN; PROSTATE CARCINOMA;
SIGNALING PATHWAY; TRANSGENIC MICE; MOUSE MODEL; EXPRESSION
AB Protein dynamics, modifications and trafficking are all processes that can modulate protein activity. Accumulating evidence strongly suggests that many proteins have distinctive roles dependent on cellular location. Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) is a transforming growth factor-beta (TGF-beta) superfamily protein that has a role in cancer, obesity and inflammation. NAG-1 is synthesized and cleaved into a mature peptide, which is ultimately secreted into the extracellular matrix (ECM). In this study, we have found that full-length NAG-1 is expressed in not only the cytoplasm and ECM, but also in the nucleus. NAG-1 is dynamically moved to the nucleus, exported into cytoplasm and further transported into the ECM. We have also found that nuclear NAG-1 contributes to inhibition of the Smad pathway by interrupting the Smad complex. Overall, our study indicates that NAG-1 is localized in the nucleus and provides new evidence that NAG-1 controls transcriptional regulation in the Smad pathway.
C1 [Min, K-W; Liggett, J. L.; Silva, G.; Baek, S. J.] Univ Tennessee, Coll Vet Med, Dept Biomed & Diagnost Sci, 2407 River Dr, Knoxville, TN 37996 USA.
[Wu, W. W.; Wang, R.; Shen, R-F] US FDA, CBER, Facil Biotechnol Resources, Bethesda, MD 20014 USA.
[Eling, T. E.] NIEHS, Mol Carcinogenesis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Min, K-W] Med Univ S Carolina, Dept Cell & Mol Pharmacol, Charleston, SC 29425 USA.
RP Baek, SJ (reprint author), Univ Tennessee, Coll Vet Med, Dept Biomed & Diagnost Sci, 2407 River Dr, Knoxville, TN 37996 USA.
EM sbaek2@utk.edu
RI Silva, Gabriel/D-7731-2017;
OI Silva, Gabriel/0000-0002-5660-9769; Min, Kyung-Won/0000-0002-8718-3588
FU National Institutes of Health [R01CA108975]; Center of Excellence in
Livestock Diseases and Human Health, University of Tennessee; CAPES
Foundation, Brazil [BEX 3159/14-0]; NIH, NIEHS Intramural Research
Program [Z01-ES010016-14]
FX We thank Dr Xingya Wang (College of Pharmaceutical Science, Zhejiang
Chinese Medical University, China) and Ms Misty Bailey (University of
Tennessee) for their critical reading of the manuscript. We also thank
Dr John Dunlap (Advanced Microscopy and Imaging Center at The University
of Tennessee) for providing technical help on confocal microscopy. This
work was supported by the National Institutes of Health (R01CA108975),
and the Center of Excellence in Livestock Diseases and Human Health,
University of Tennessee, to SJB and a grant (BEX 3159/14-0) from the
CAPES Foundation, Brazil (GS). This research was also supported, in
part, by the NIH, NIEHS Intramural Research Program (TEE)
Z01-ES010016-14.
NR 68
TC 5
Z9 5
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD JAN 21
PY 2016
VL 35
IS 3
BP 377
EP 388
DI 10.1038/onc.2015.95
PG 12
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA DC2OF
UT WOS:000369055300011
PM 25893289
ER
PT J
AU Eichelberger, MC
Couzens, L
Gao, YH
Levine, M
Katz, J
Wagner, R
Thompson, CI
Hoschler, K
Laurie, K
Bai, T
Engelhardt, OG
Wood, J
AF Eichelberger, Maryna C.
Couzens, Laura
Gao, Yonghong
Levine, Min
Katz, Jacqueline
Wagner, Ralf
Thompson, Catherine I.
Hoeschler, Katja
Laurie, Karen
Bai, Tian
Engelhardt, Othmar G.
Wood, John
CA ELLA Study Participants
TI Comparability of neuraminidase inhibition antibody titers measured by
enzyme-linked lectin assay (ELLA) for the analysis of influenza vaccine
immunogenicity
SO VACCINE
LA English
DT Article
DE Influenza; Neuraminidase; Assay; Variability; CONSISE; ELLA
ID VIRUS; STANDARD; A(H3N2)
AB Neuraminidase-inhibition (NI) antibody titers can be used to evaluate the immunogenicity of inactivated influenza vaccines and have provided evidence of serologic cross-reactivity between seasonal and pandemic H1N1 viruses. The traditional thiobarbituric acid assay is impractical for large serologic analyses, and therefore many laboratories use an enzyme-linked lectin assay (ELLA) to determine serum NI antibody titers. The comparability of ELLA NI antibody titers when measured in different laboratories was unknown. Here we report a study conducted through the Consortium for the Standardisation of Influenza SeroEpidemiology (CONSISE) to evaluate the variability of the ELLA. NI antibody titers of a set of 12 samples were measured against both N1 and N2 neuraminidase antigens in 3 independent assays by each of 23 laboratories. For a sample repeated in the same assay, >= 96% of N1 and N2 assays had less than a 4-fold difference in titer. Comparison of the titers measured in assays conducted on 3 different days in the same laboratory showed that a four-fold difference in titer was uncommon. Titers of the same sera measured in different laboratories spanned 3 to 6 two-fold dilutions (i.e., 8-64 fold difference in titer), with an average percent geometric coefficient of variation (%GCV) of 112 and 82% against N1 and N2 antigens, respectively. The difference in titer as indicated by fold range and %GCV was improved by normalizing the NI titers to a standard that was included in each assay. This study identified background signal and the amount of antigen in the assay as critical factors that influence titer, providing important information toward development of a consensus ELLA protocol. Published by Elsevier Ltd.
C1 [Eichelberger, Maryna C.; Couzens, Laura] US FDA, Div Viral Prod, CBER, Silver Spring, MD USA.
[Gao, Yonghong] US Dept HHS, BARDA, Washington, DC 20201 USA.
[Levine, Min; Katz, Jacqueline] Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA USA.
[Wagner, Ralf] Paul Ehrlich Inst, Langen, Germany.
[Thompson, Catherine I.; Hoeschler, Katja] Publ Hlth England, London, England.
[Laurie, Karen] WHO Collaborating Ctr, Melbourne, Vic, Australia.
[Bai, Tian] Natl Inst Viral Dis Control & Prevent, WHO Collaborating Ctr, Beijing, Peoples R China.
[Engelhardt, Othmar G.] Med & Healthcare Prod Regulatory Agcy, Natl Inst Biol Stand & Control, Potters Bar, Herts, England.
[Wood, John] Natl Inst Biol Stand & Controls, New York, NY USA.
RP Eichelberger, MC (reprint author), US FDA, Div Viral Prod, CBER, Silver Spring, MD USA.
EM Maryna.Eichelberger@fda.hhs.gov
FU Intramural Research Program of the NIH, NIAID; BARDA interagency
agreement [224-14-1010]
FX We are indebted to Maria van Kerkhove for providing leadership and
advice throughout this study, and Mario Barro for suggestions and
support. This research was supported in part by the Intramural Research
Program of the NIH, NIAID and BARDA interagency agreement #224-14-1010.
We thank Drs. David Evers, Sara Gagneten, and Steven Rubin for critical
review of the manuscript.
NR 18
TC 2
Z9 2
U1 0
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD JAN 20
PY 2016
VL 34
IS 4
BP 458
EP 465
DI 10.1016/j.vaccine.2015.12.022
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA DB9WJ
UT WOS:000368868100011
PM 26707221
ER
PT J
AU Ponnusamy, D
Kozlova, EV
Sha, J
Erova, TE
Azar, SR
Fitts, EC
Kirtley, ML
Tiner, BL
Andersson, JA
Grim, CJ
Isom, RP
Hasan, NA
Colwell, RR
Chopra, AK
AF Ponnusamy, Duraisamy
Kozlova, Elena V.
Sha, Jian
Erova, Tatiana E.
Azar, Sasha R.
Fitts, Eric C.
Kirtley, Michelle L.
Tiner, Bethany L.
Andersson, Jourdan A.
Grim, Christopher J.
Isom, Richard P.
Hasan, Nur A.
Colwell, Rita R.
Chopra, Ashok K.
TI Cross-talk among flesh-eating Aeromonas hydrophila strains in mixed
infection leading to necrotizing fasciitis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Aeromonas hydrophila; necrotizing fasciitis; mixed infections;
intramuscular mouse model; metagenomics
ID PSEUDOMONAS-AERUGINOSA; VIRULENCE FACTORS; GAS-GANGRENE; EXOTOXIN;
PATIENT; WATER; HOST
AB Necrotizing fasciitis (NF) caused by flesh-eating bacteria is associated with high case fatality. In an earlier study, we reported infection of an immunocompetent individual with multiple strains of Aeromonas hydrophila (NF1-NF4), the latter three constituted a clonal group whereas NF1 was phylogenetically distinct. To understand the complex interactions of these strains in NF pathophysiology, a mouse model was used, whereby either single or mixed A. hydrophila strains were injected intramuscularly. NF2, which harbors exotoxin A (exoA) gene, was highly virulent when injected alone, but its virulence was attenuated in the presence of NF1 (exoA-minus). NF1 alone, although not lethal to animals, became highly virulent when combined with NF2, its virulence augmented by cis-exoA expression when injected alone in mice. Based on metagenomics and microbiological analyses, it was found that, in mixed infection, NF1 selectively disseminated to mouse peripheral organs, whereas the other strains (NF2, NF3, and NF4) were confined to the injection site and eventually cleared. In vitro studies showed NF2 to be more effectively phagocytized and killed by macrophages than NF1. NF1 inhibited growth of NF2 on solid media, but ExoA of NF2 augmented virulence of NF1 and the presence of NF1 facilitated clearance of NF2 from animals either by enhanced priming of host immune system or direct killing via a contact-dependent mechanism.
C1 [Ponnusamy, Duraisamy; Kozlova, Elena V.; Sha, Jian; Erova, Tatiana E.; Azar, Sasha R.; Fitts, Eric C.; Kirtley, Michelle L.; Tiner, Bethany L.; Andersson, Jourdan A.; Chopra, Ashok K.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA.
[Grim, Christopher J.] US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Laurel, MD 20708 USA.
[Isom, Richard P.; Hasan, Nur A.; Colwell, Rita R.] CosmosID Inc, Rockville, MD 20850 USA.
[Hasan, Nur A.; Colwell, Rita R.] Univ Maryland, Inst Adv Comp Studies, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA.
[Colwell, Rita R.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
RP Colwell, RR (reprint author), CosmosID Inc, Rockville, MD 20850 USA.
EM rcolwell@umiacs.umd.edu; achopra@utmb.edu
FU Leon Bromberg and Robert E. Shope endowment, University of Texas Medical
Branch; Robert E. Shope and John S. Dunn Distinguished Chair in Global
Health endowment, University of Texas Medical Branch; NIH
[2RO1A1039129]; James W. McLaughlin Postdoctoral Fellowship; WHO
Collaborating Center for Vaccine Development, UTMB; T32 Biodefense
Training Grant [AI060549]
FX Financial support was provided to A.K.C. through Leon Bromberg and
Robert E. Shope and John S. Dunn Distinguished Chair in Global Health
endowments, University of Texas Medical Branch, and NIH Grant
2RO1A1039129 was awarded to R.R.C. D.P. was supported in part by the
James W. McLaughlin Postdoctoral Fellowship. B.L.T. and J.A.A. were
supported in part by the WHO Collaborating Center for Vaccine
Development, UTMB. E.C.F. was supported in part by T32 Biodefense
Training Grant AI060549.
NR 23
TC 4
Z9 4
U1 1
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 19
PY 2016
VL 113
IS 3
BP 722
EP 727
DI 10.1073/pnas.1523817113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB4BX
UT WOS:000368458800068
PM 26733683
ER
PT J
AU Pettengill, EA
Pettengill, JB
Binet, R
AF Pettengill, Emily A.
Pettengill, James B.
Binet, Rachel
TI Phylogenetic Analyses of Shigella and Enteroinvasive Escherichia coli
for the Identification of Molecular Epidemiological Markers:
Whole-Genome Comparative Analysis Does Not Support Distinct Genera
Designation
SO FRONTIERS IN MICROBIOLOGY
LA English
DT Article
DE Shigella; enteroinvasive E. coli (EIEC); phylogeny; whole genome
sequencing; classification; epidemiological markers
ID MULTILOCUS GENOTYPE DATA; POPULATION-STRUCTURE; RAPID DETECTION;
DIARRHEA; EVOLUTION; PATHOGENS; INFERENCE; GENETICS; STRAINS; ORIGINS
AB As a leading cause of bacterial dysentery, Shigella represents a significant threat to public health and food safety. Related, but often overlooked, enteroinvasive Escherichia coli (EIEC) can also cause dysentery. Current typing methods have limited ability to identify and differentiate between these pathogens despite the need for rapid and accurate identification of pathogens for clinical treatment and outbreak response. We present a comprehensive phylogeny of Shigella and EIEC using whole genome sequencing of 169 samples, constituting unparalleled strain diversity, and observe a lack of monophyly between Shigella and EIEC and among Shigella taxonomic groups. The evolutionary relationships in the phylogeny are supported by analyses of population structure and hierarchical clustering patterns of translated gene homolog abundance. Lastly, we identified a panel of 404 single nucleotide polymorphism (SNP) markers specific to each phylogenetic cluster for more accurate identification of Shigella and EIEC. Our findings show that Shigella and EIEC are not distinct evolutionary groups within the E. coli genus and, thus, EIEC as a group is not the ancestor to Shigella. The multiple analyses presented provide evidence for reconsidering the taxonomic placement of Shigella. The SNP markers offer more discriminatory power to molecular epidemiological typing methods involving these bacterial pathogens.
C1 [Pettengill, Emily A.; Binet, Rachel] US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Pettengill, James B.] US FDA, Div Publ Hlth Informat & Analyt, Off Analyt & Outreach, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
RP Binet, R (reprint author), US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
EM rachel.binet@fda.hhs.gov
FU Research Participation Program at the Center for Food Safety and Applied
Nutrition; U.S. Department of Energy; U.S. Food and Drug Administration
FX EP was funded in part by an appointment with the Research Participation
Program at the Center for Food Safety and Applied Nutrition administered
by Oak Ridge Institute for Science and Education through and interagency
agreement between the U.S. Department of Energy and The U.S. Food and
Drug Administration.
NR 58
TC 3
Z9 3
U1 2
U2 8
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-302X
J9 FRONT MICROBIOL
JI Front. Microbiol.
PD JAN 19
PY 2016
VL 6
AR 1573
DI 10.3389/fmicb.2015.01573
PG 11
WC Microbiology
SC Microbiology
GA DB3BW
UT WOS:000368386000001
ER
PT J
AU Qu, HO
Mudalige, TK
Linder, SW
AF Qu, Haiou
Mudalige, Thilak K.
Linder, Sean W.
TI Capillary electrophoresis coupled with inductively coupled mass
spectrometry as an alternative to cloud point extraction based methods
for rapid quantification of silver ions and surface coated silver
nanoparticles
SO JOURNAL OF CHROMATOGRAPHY A
LA English
DT Article
DE Silver nanoparticles; Ionic silver; Speciation and quantification;
Capillary electrophoresis; Inductively coupled mass spectrometry
ID FIELD FLOW FRACTIONATION; ANTIBACTERIAL PRODUCTS; ENVIRONMENTAL WATERS;
DIETARY-SUPPLEMENTS; GOLD NANOPARTICLES; ICP-MS; SEPARATION; SPECIATION;
TRANSFORMATION; CYTOTOXICITY
AB Speciation and accurate quantification of ionic silver and metallic silver nanoparticles are critical to investigate silver toxicity and to determine the shelf-life of products that contain nano silver under various storage conditions. We developed a rapid method for quantification of silver ions and silver nanoparticles using capillary electrophoresis (CE) interfaced with inductively-coupled plasma mass spectrometry (ICPMS). The addition of 2-mercaptopropionylglycine (tiopronin) to the background electrolyte was used to facilitate the chromatographic separation of ionic silver and maintain the oxidation state of silver. The obtained limits of detection were 0.05 mu g kg(-1) of silver nanoparticles and 0.03 mu g kg(-1) of ionic silver. Nanoparticles of varied sizes (10-110 nm) with different surface coating, including citrate acid, lipoic acid, polyvinylpyrrolidone and bovine serum albumin (BSA) were successfully analyzed. Particularly good recoveries (>93%) were obtained for both ionic silver and silver nanoparticle in the presence of excess amount of BSA. The method was further tested with six commercially available dietary supplements which varied in concentration and matrix components. The summed values of silver ions and silver nanoparticles correlated well with the total silver concentration determined by ICPMS after acid digestion. This method can serve as an alternative to cloud point extraction technique when the extraction efficiency for protein coated nanoparticles is low. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Qu, Haiou; Mudalige, Thilak K.; Linder, Sean W.] US FDA, Off Regulatory Affairs, Arkansas Reg Lab, 3900 NCTR Rd, Jefferson, AR 72079 USA.
RP Mudalige, TK; Linder, SW (reprint author), US FDA, Off Regulatory Affairs, Arkansas Reg Lab, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM Thilak.Mudalige@fda.hhs.gov; Sean.Linder@fda.hhs.gov
FU Intramural FDA HHS [FD999999]
NR 26
TC 5
Z9 5
U1 24
U2 61
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0021-9673
EI 1873-3778
J9 J CHROMATOGR A
JI J. Chromatogr. A
PD JAN 15
PY 2016
VL 1429
BP 348
EP 353
DI 10.1016/j.chroma.2015.12.033
PG 6
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA DC9RQ
UT WOS:000369559100038
PM 26724893
ER
PT J
AU Marks, NS
AF Marks, Norman S.
TI Dietary Supplements: How Family Physicians Can Address Safety Concerns
by Working with the FDA
SO AMERICAN FAMILY PHYSICIAN
LA English
DT Editorial Material
ID CAFFEINE
C1 [Marks, Norman S.] US FDA, Silver Spring, MD USA.
EM normarks@gmail.com
NR 22
TC 0
Z9 0
U1 0
U2 0
PU AMER ACAD FAMILY PHYSICIANS
PI KANSAS CITY
PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA
SN 0002-838X
EI 1532-0650
J9 AM FAM PHYSICIAN
JI Am. Fam. Physician
PD JAN 15
PY 2016
VL 93
IS 2
BP 97
EP 98
PG 2
WC Primary Health Care; Medicine, General & Internal
SC General & Internal Medicine
GA DB2ZR
UT WOS:000368379700003
PM 26926404
ER
PT J
AU Huque, MF
AF Huque, Mohammad F.
TI Validity of the Hochberg procedure revisited for clinical trial
applications
SO STATISTICS IN MEDICINE
LA English
DT Article
DE Hochberg procedure; correlated tests; type I error rate control; primary
endpoints; truncated Hochberg procedure
ID IMPROVED BONFERRONI PROCEDURE; MULTIPLE TESTS; INEQUALITIES; VARIABLES
AB There is much interest in using the Hochberg procedure (HP) for statistical tests on primary endpoints of confirmatory clinical trials. The procedure is simple to use and enjoys more power than the Bonferroni and the Holm procedures. However, the HP is not assumption free like the other two procedures. It controls the familywise type I error rate when test statistics (used for statistical tests) are independent or if dependent satisfy a conditionally independent formulation. Otherwise, its properties for dependent tests at present are not fully understood. Consequently, its use for confirmatory trials, especially for their primary endpoints, remains worrisome. Confirmatory trials are typically designed with 1-2 primary endpoints. Therefore, a question was raised at the Food and Drug Administration as to whether the HP is a valid test for the simple case of performing treatment-to-control comparisons on two primary endpoints when their test statistics are not independent. Confirmatory trials for statistical tests normally use simple test statistics, such as the normal Z, student's t, and chi-square. The literature does include some work on the HP for dependent cases covering these test statistics, but concerns remain regarding its use for confirmatory trials for which endpoint tests are mostly of the dependent kind. The purpose of this paper is therefore to revisit this procedure and provide sufficient details for better understanding of its performance for dependent cases related to the aforementioned question. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Huque, Mohammad F.] CDER, FDA, OTS, Off Biostat, Silver Spring, MD 20993 USA.
RP Huque, MF (reprint author), US FDA, Div Biometr 4, Silver Spring, MD 20993 USA.
EM Mohammad.Huque@fda.hhs.gov
NR 21
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD JAN 15
PY 2016
VL 35
IS 1
BP 5
EP 20
DI 10.1002/sim.6617
PG 16
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA DA7GF
UT WOS:000367971900001
PM 26278421
ER
PT J
AU Ammann, EM
Jones, MP
Link, BK
Carnahan, RM
Winiecki, SK
Torner, JC
McDowell, BD
Fireman, BH
Chrischilles, EA
AF Ammann, Eric M.
Jones, Michael P.
Link, Brian K.
Carnahan, Ryan M.
Winiecki, Scott K.
Torner, James C.
McDowell, Bradley D.
Fireman, Bruce H.
Chrischilles, Elizabeth A.
TI Intravenous immune globulin and thromboembolic adverse events in
patients with hematologic malignancy
SO BLOOD
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; PROPENSITY SCORE METHODS; HEALTH-CARE
DATABASE; VENOUS THROMBOEMBOLISM; IMMUNOGLOBULIN THERAPY; ADMINISTRATIVE
DATA; THROMBOTIC EVENTS; MULTIPLE-MYELOMA; PREDICTIVE-VALUE;
UNITED-STATES
AB In patients with hypogammaglobulinemia secondary to chronic lymphocytic leukemia (CLL) or multiple myeloma(MM), intravenous immune globulin (IVIg) may be administered to reduce the risk of infection. Since 2013, IVIg products have carried a boxed safety warning about the risk of thromboembolic events (TEEs), with TEEs reported in 0.5% to 15% of patients treated with IVIg. In this retrospective cohort study of older patients with CLL or MM identified from the Surveillance, Epidemiology, and End Results-Medicare Linked Database, we assessed rates of clinically serious TEEs in 2724 new users of IVIg and a propensity-matched comparison group of 8035 nonusers. For the primary end point, arterial TEE, we observed a transient increased risk of TEE during the day of an IVIg infusion and the day afterward (hazard ration = 3.40; 95% confidence interval [CI]: 1.25, 9.25); this risk declined over the remainder of the 30-day treatment cycle. When considered in terms of absolute risk averaged over a 1-year treatment period, the increase in risk attributable to IVIg was estimated to be 0.7% (95% CI: -0.2%, 2.0%) compared with a baseline risk of 1.8% for the arterial TEE end point. A statistically nonsignificant risk increase of 0.3% (95% CI: -0.4%, 1.5%) compared with a baseline risk of 1.1% was observed for the venous TEE end point. Further research is needed to establish the generalizability of these results to patients receiving higher doses of IVIg for other indications.
C1 [Ammann, Eric M.; Carnahan, Ryan M.; Torner, James C.; Chrischilles, Elizabeth A.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA.
[Jones, Michael P.] Univ Iowa, Coll Publ Hlth, Dept Biostat, Iowa City, IA USA.
[Link, Brian K.] Univ Iowa, Dept Internal Med, Div Hematol Oncol & Blood & Marrow Transplantat, Carver Coll Med, Iowa City, IA 52242 USA.
[Winiecki, Scott K.] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
[McDowell, Bradley D.; Chrischilles, Elizabeth A.] Univ Iowa Hosp & Clin, Populat Res Core, Holden Comprehens Canc Ctr, Iowa City, IA 52242 USA.
[Fireman, Bruce H.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
RP Ammann, EM (reprint author), Dept Epidemiol 400 CPHB, 145 N Riverside Dr, Iowa City, IA 52242 USA.
EM eric-ammann@uiowa.edu
FU NCCDPHP CDC HHS [U58 DP003862, U58DP003862-01]; NCI NIH HHS
[HHSN261201000034C, HHSN261201000035I, HHSN261201000140C, P30 CA086862];
None [HHSN261201000035C]; PHS HHS [HHSF22301006T, HHSF223200910006I,
HHSN261201000035C, HHSN2612010000CRC, HHSN261201000140C]
NR 49
TC 4
Z9 4
U1 1
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JAN 14
PY 2016
VL 127
IS 2
BP 200
EP 207
DI 10.1182/blood-2015-05-647552
PG 8
WC Hematology
SC Hematology
GA DC5UG
UT WOS:000369285400009
PM 26443622
ER
PT J
AU Joffe, HV
Chang, C
Sewell, C
Easley, O
Nguyen, C
Dunn, S
Lehrfeld, K
Lee, LM
Kim, MJ
Slagle, AF
Beitz, J
AF Joffe, Hylton V.
Chang, Christina
Sewell, Catherine
Easley, Olivia
Nguyen, Christine
Dunn, Somya
Lehrfeld, Kimberly
Lee, LaiMing
Kim, Myong-Jin
Slagle, Ashley F.
Beitz, Julie
TI FDA Approval of Flibanserin - Treating Hypoactive Sexual Desire Disorder
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Joffe, Hylton V.; Chang, Christina; Sewell, Catherine; Easley, Olivia; Nguyen, Christine; Dunn, Somya; Lehrfeld, Kimberly; Lee, LaiMing; Kim, Myong-Jin; Slagle, Ashley F.; Beitz, Julie] Food & Drug Adm, Silver Spring, MD 20993 USA.
RP Joffe, HV (reprint author), Food & Drug Adm, Silver Spring, MD 20993 USA.
NR 5
TC 7
Z9 7
U1 2
U2 7
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JAN 14
PY 2016
VL 374
IS 2
BP 101
EP 104
DI 10.1056/NEJMp1513686
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA DA7PQ
UT WOS:000367996700002
PM 26649985
ER
PT J
AU Compton, WM
Jones, CM
Baldwin, GT
AF Compton, Wilson M.
Jones, Christopher M.
Baldwin, Grant T.
TI Relationship between Nonmedical Prescription-Opioid Use and Heroin Use
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Review
ID NEW-YORK-CITY; INJECTION-DRUG USERS; UNITED-STATES; OVERDOSE DEATHS;
RISK BEHAVIORS; YOUNG-ADULTS; ABUSE; EPIDEMIC; MISUSE; DEPENDENCE
C1 [Compton, Wilson M.] NIDA, NIH, Silver Spring, MD USA.
[Jones, Christopher M.] US FDA, Silver Spring, MD USA.
[Baldwin, Grant T.] Ctr Dis Control & Prevent, Div Unintent Injury Prevent, Atlanta, GA USA.
RP Compton, WM (reprint author), NIDA, NIH, 6001 Execut Blvd,MSC 9581, Bethesda, MD 20892 USA.
EM wcompton@nida.nih.gov
NR 65
TC 74
Z9 74
U1 9
U2 38
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JAN 14
PY 2016
VL 374
IS 2
BP 154
EP 163
DI 10.1056/NEJMra1508490
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA DA7PQ
UT WOS:000367996700010
PM 26760086
ER
PT J
AU Hakk, H
Shappell, NW
Lupton, SJ
Shelver, WL
Fanaselle, W
Oryang, D
Yeung, CY
Hoelzer, K
Ma, YQ
Gaalswyk, D
Pouillot, R
Van Doren, JM
AF Hakk, Heldur
Shappell, Nancy W.
Lupton, Sara J.
Shelver, Weilin L.
Fanaselle, Wendy
Oryang, David
Yeung, Chi Yuen
Hoelzer, Karin
Ma, Yinqing
Gaalswyk, Dennis
Pouillot, Regis
Van Doren, Jane M.
TI Distribution of Animal Drugs between Skim Milk and Milk Fat Fractions in
Spiked Whole Milk: Understanding the Potential Impact on Commercial Milk
Products
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE veterinary drug residues; cream; antibiotics; anthelmintics; NSAID;
partitioning distribution; milk
ID IVERMECTIN RESIDUES; DAIRY SHEEP; CHEESE; ANTIBIOTICS; STABILITY;
STORAGE; EPRINOMECTIN; INACTIVATION; ERYTHROMYCIN; ALBENDAZOLE
AB Seven animal drugs [penicillin G (PENG), sulfadimethomine (SDMX), oxytetracycline (OTET), erythromycin (ERY), ketoprofen (KETO), thiabendazole (THIA), and ivermectin (IVR)] were used to evaluate the drug distribution between milk fat and skim milk fractions of cow milk. More than 90% of the radioactivity was distributed into the skim milk fraction for ERY, KETO, OTET, PENG, and SDMX, approximately 80% for THIA, and 13% for IVR. The distribution of drug between milk fat and skim milk fractions was significantly correlated to the drug's lipophilicity (partition coefficient, log P, or distribution coefficient, log D, which includes ionization). Data were fit with linear mixed effects models; the best fit was obtained within this data set with log D versus observed drug distribution ratios. These candidate empirical models serve for assisting to predict the distribution and concentration of these drugs in a variety of milk and milk products.
C1 [Hakk, Heldur; Shappell, Nancy W.; Lupton, Sara J.; Shelver, Weilin L.] ARS, Biosci Res Lab, USDA, Fargo, ND 58102 USA.
[Fanaselle, Wendy; Oryang, David; Yeung, Chi Yuen; Hoelzer, Karin; Ma, Yinqing; Gaalswyk, Dennis; Pouillot, Regis; Van Doren, Jane M.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
RP Hakk, H (reprint author), ARS, Biosci Res Lab, USDA, 1605 Albrecht Blvd, Fargo, ND 58102 USA.
EM Heldur.Hakk@ars.usda.gov
RI Pouillot, Regis/E-8103-2010;
OI Pouillot, Regis/0000-0002-6107-5212; Lupton, Sara/0000-0002-4566-595X
FU FDA; USDA ARS [224-14-2006]
FX This study was collaboratively funded by an interagency agreement with
the FDA and USDA ARS (Interagency Agreement 224-14-2006) and, in part,
by an appointment (K.H.) to the Research Participation Program at the
Center for Food Safety and Applied Nutrition administered by the Oak
Ridge Institute for Science and Education through an interagency
agreement between the U.S. Department of Energy and the U.S. Food and
Drug Administration. This work was completed while K.H. was an ORISE
Fellow for the FDA.
NR 34
TC 1
Z9 1
U1 2
U2 16
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0021-8561
EI 1520-5118
J9 J AGR FOOD CHEM
JI J. Agric. Food Chem.
PD JAN 13
PY 2016
VL 64
IS 1
BP 326
EP 335
DI 10.1021/acs.jafc.5b04726
PG 10
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA DB2FE
UT WOS:000368322900042
PM 26652058
ER
PT J
AU Kindrat, I
Tryndyak, V
de Conti, A
Shpyleva, S
Mudalige, TK
Kobets, T
Erstenyuk, AM
Beland, FA
Pogribny, IP
AF Kindrat, Iryna
Tryndyak, Volodymyr
de Conti, Aline
Shpyleva, Svitlana
Mudalige, Thilak K.
Kobets, Tetyana
Erstenyuk, Anna M.
Beland, Frederick A.
Pogribny, Igor P.
TI MicroRNA-152-mediated dysregulation of hepatic transferrin receptor 1 in
liver carcinogenesis
SO ONCOTARGET
LA English
DT Article
DE hepatocellular carcinoma; iron metabolism; transferrin receptor 1;
microRNA-152; dysregulation
ID IRON REGULATORY PROTEINS; HEPATOCELLULAR-CARCINOMA; EXPRESSION; RAT;
CELLS; CANCER; GROWTH; 2-ACETYLAMINOFLUORENE; METABOLISM; ACTIVATION
AB Over-expression of transferrin receptor 1 (TFRC) is observed in hepatocellular carcinoma (HCC); however, there is a lack of conclusive information regarding the mechanisms of this dysregulation. In the present study, we demonstrated a significant increase in the levels of TFRC mRNA and protein in preneoplastic livers from relevant experimental models of human hepatocarcinogenesis and in human HCC cells. Additionally, using the TCGA database, we demonstrated an over-expression of TFRC in human HCC tissue samples and a markedly decreased level of microRNA-152 (miR-152) when compared to non-tumor liver tissue. The results indicated that the increase in levels of TFRC in human HCC cells and human HCC tissue samples may be attributed, in part, to a post-transcriptional mechanism mediated by a downregulation of miR-152. This was evidenced by a strong inverse correlation between the level of TFRC and the expression of miR-152 in human HCC cells (r = -0.99, p = 4. 7 x 10(-9)), and was confirmed by in vitro experiments showing that transfection of human HCC cell lines with miR-152 effectively suppressed TFRC expression. This suggests that miR-152-specific targeting of TFRC may provide a selective anticancer therapeutic approach for the treatment of HCC.
C1 [Kindrat, Iryna; Tryndyak, Volodymyr; de Conti, Aline; Shpyleva, Svitlana; Kobets, Tetyana; Beland, Frederick A.; Pogribny, Igor P.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
[Mudalige, Thilak K.] US FDA, Off Regulatory Affairs, Arkansas Reg Lab, Jefferson, AR USA.
[Kindrat, Iryna; Erstenyuk, Anna M.] Ivano Frankivsk Natl Med Univ, Dept Biol & Med Chem, Ivano Frankivsk, Ukraine.
RP Pogribny, IP (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
EM igor.pogribny@fda.hhs.gov
FU NCTR
FX This work was supported in part by appointment (I.K., A.d.C., and T.K.)
to the Postgraduate Research Program at the NCTR administered by the Oak
Ridge Institute for Science and Education (ORISE). The views expressed
in this manuscript do not necessarily represent those of the U.S. Food
and Drug Administration.
NR 49
TC 1
Z9 2
U1 1
U2 1
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JAN 12
PY 2016
VL 7
IS 2
BP 1276
EP 1287
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DD5GP
UT WOS:000369951100016
PM 26657500
ER
PT J
AU Duff, MR
Chopra, S
Strader, MB
Agarwal, PK
Howell, EE
AF Duff, Michael R., Jr.
Chopra, Shaileja
Strader, Michael Brad
Agarwal, Pratul K.
Howell, Elizabeth E.
TI Tales of Dihydrofolate Binding to R67 Dihydrofolate Reductase
SO BIOCHEMISTRY
LA English
DT Article
ID ACTIVE-SITE PORE; TERNARY COMPLEX; LIGAND-BINDING; ENZYME CATALYSIS;
PROTEIN; MUTATIONS; RESIDUES; PURIFICATION; DYNAMICS; FOLATE
AB Homotetrameric R67 dihydrofolate reductase possesses 222 symmetry and a single active site pore. This situation results in a promiscuous binding site that accommodates either the substrate, dihydrofolate (DHF), or the cofactor, NADPH. NADPH interacts more directly with the protein as it is larger than the substrate. In contrast, the p-aminobenzoyl-glutamate tail of DHF, as monitored by nuclear magnetic resonance and crystallography, is disordered when bound. To explore whether smaller active site volumes (which should decrease the level of tail disorder by confinement effects) alter steady state rates, asymmetric mutations that decreased the half-pore volume by similar to 35% were constructed. Only minor effects on k(cat) were observed. To continue exploring the role of tail disorder in catalysis, 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide-mediated cross-linking between R67 DHFR and folate was performed. A two-folate, one-tetramer complex results in the loss of enzyme activity where two symmetry-related K32 residues in the protein are cross-linked to the carboxylates of two bound folates. The tethered folate could be reduced, although with a <= 30-fold decreased rate, suggesting decreased dynamics and/or suboptimal positioning of the cross-linked folate for catalysis. Computer simulations that restrain the dihydrofolate tail near 1(32 indicate that cross-linking still allows movement of the p-aminobenzoyl ring, which allows the reaction to occur. Finally, a bis-ethylene-diamine-alpha,gamma-amide folate adduct was synthesized; both negatively charged carboxylates in the glutamate tail were replaced with positively charged amines. The K-i for this adduct was similar to 9-fold higher than for folate. These various results indicate a balance between folate tail disorder, which helps the enzyme bind substrate while dynamics facilitates catalysis.
C1 [Duff, Michael R., Jr.; Chopra, Shaileja; Agarwal, Pratul K.; Howell, Elizabeth E.] Univ Tennessee, Dept Biochem & Cellular & Mol Biol, Knoxville, TN 37996 USA.
[Strader, Michael Brad] US FDA, Lab Biochem & Vasc Biol, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
[Agarwal, Pratul K.] Oak Ridge Natl Lab, Comp Sci & Math Div, Oak Ridge, TN 37831 USA.
RP Howell, EE (reprint author), Univ Tennessee, Dept Biochem Cellular & Mol Biol, Knoxville, TN 37996 USA.
EM lzh@utk.edu
FU National Science Foundation [MCB-0817827]; National Institutes of Health
[GM 110669, GM105978]
FX This work was supported by National Science Foundation Grant MCB-0817827
to E.E.H. and in part by National Institutes of Health Grants GM 110669
(to E.E.H.) and GM105978 (to P.K.A.).
NR 65
TC 1
Z9 1
U1 2
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD JAN 12
PY 2016
VL 55
IS 1
BP 133
EP 145
DI 10.1021/acs.biochem.5b00981
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DB2FF
UT WOS:000368323000014
PM 26637016
ER
PT J
AU Karzai, F
Madan, RA
Ning, YM
Theoret, MR
Arlen, PM
Parnes, HL
Ojemuyiwa, MA
Strauss, J
Dawson, NA
McLeod, DG
Harold, N
Couvillon, A
Cordes, LM
Chen, C
Steinberg, SM
Sissung, TM
Price, DK
Gulley, JL
Figg, WD
Dahut, WL
AF Karzai, Fatima
Madan, Ravi Amrit
Ning, Yang-Min
Theoret, Marc Robert
Arlen, Philip M.
Parnes, Howard L.
Ojemuyiwa, Michelle A.
Strauss, Julius
Dawson, Nancy Ann
McLeod, David G.
Harold, Nancy
Couvillon, Anna
Cordes, Lisa M.
Chen, Clara
Steinberg, Seth M.
Sissung, Tristan M.
Price, Douglas K.
Gulley, James L.
Figg, William Douglas
Dahut, William L.
TI Comparison of survival of African-American (AA) patients (pts) in
docetaxel (D)-based combination therapies in metastatic
castrate-resistant prostate cancer (mCRPC).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Genitourinary Cancers Symposium
CY JAN 07-09, 2016
CL San Francisco, CA
C1 NCI, NIH, Bethesda, MD 20892 USA.
NCI, Genitourinary Malignancies Branch, CCR, NIH, Bethesda, MD 20892 USA.
US FDA, Silver Spring, MD USA.
NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
Walter Reed Natl Mil Med Ctr, Rockville, MD USA.
Lombardi Comprehens Canc Ctr, Washington, DC USA.
Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
NIH, Bldg 10, Bethesda, MD 20892 USA.
NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD USA.
NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
NCI, Mol Pharmacol Program, NIH, Bethesda, MD 20892 USA.
NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA.
NCI, Clin Pharmacol Program, NIH, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016
OI Gulley, James/0000-0002-6569-2912;
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 10
PY 2016
VL 34
IS 2
SU S
MA 272
PG 2
WC Oncology
SC Oncology
GA DO9LW
UT WOS:000378109100271
ER
PT J
AU Ning, YMM
Chen, C
Maher, VE
Xu, JX
Kim, G
Pazdur, R
AF Ning, Yangmin M.
Chen, Clara
Maher, Virginia Ellen
Xu, James Xunhai
Kim, Geoffrey
Pazdur, Richard
TI Tumor progression versus bone scan "flare" in new lesions detected on
early bone scans in patients with chemo-naive metastatic castration
resistant prostate cancer (mCRPC) treated with placebo or enzalutamide
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Genitourinary Cancers Symposium
CY JAN 07-09, 2016
CL San Francisco, CA
C1 US FDA, Silver Spring, MD USA.
NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD USA.
US FDA, Washington, DC 20204 USA.
US FDA, Ellicott City, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 10
PY 2016
VL 34
IS 2
SU S
MA 305
PG 1
WC Oncology
SC Oncology
GA DO9LW
UT WOS:000378109100303
ER
PT J
AU Knolhoff, AM
Croley, TR
AF Knolhoff, Ann M.
Croley, Timothy R.
TI Non-targeted screening approaches for contaminants and adulterants in
food using liquid chromatography hyphenated to high resolution mass
spectrometry
SO JOURNAL OF CHROMATOGRAPHY A
LA English
DT Review
DE Non-targeted screening; Food safety; LC/MS; HR-MS; Unknown analysis
ID ISOTOPIC ABUNDANCE MEASUREMENTS; COLLISION-INDUCED DISSOCIATION;
QUECHERS SAMPLE PREPARATION; DENSITY-FUNCTIONAL THEORY; ACCURATE-MASS;
METABOLITE IDENTIFICATION; PESTICIDE-RESIDUES; CHEMICAL CONTAMINANTS;
METABOLOMICS ANALYSIS; SMALL MOLECULES
AB The majority of analytical methods for food safety monitor the presence of a specific compound or defined set of compounds. Non-targeted screening methods are complementary to these approaches by detecting and identifying unexpected compounds present in food matrices that may be harmful to public health. However, the development and implementation of generalized non-targeted screening workflows are particularly challenging, especially for food matrices due to inherent sample complexity and diversity and a large analyte concentration range. One approach that can be implemented is liquid chromatography coupled to high-resolution mass spectrometry, which serves to reduce this complexity and is capable of generating Molecular formulae for compounds of interest. Current capabilities, strategies, and challenges will be reviewed for sample preparation, mass spectrometry, chromatography, and data processing workflows. Considerations to increase the accuracy and speed of identifying unknown molecular species will also be addressed, including suggestions for achieving sufficient data quality for non-targeted screening applications. Published by Elsevier B.V.
C1 [Knolhoff, Ann M.; Croley, Timothy R.] US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
RP Knolhoff, AM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM Ann.Knolhoff@fda.hhs.gov
NR 111
TC 4
Z9 6
U1 24
U2 101
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0021-9673
EI 1873-3778
J9 J CHROMATOGR A
JI J. Chromatogr. A
PD JAN 8
PY 2016
VL 1428
BP 86
EP 96
DI 10.1016/j.chroma.2015.08.059
PG 11
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA DB5OR
UT WOS:000368564000007
PM 26372444
ER
PT J
AU Ulitzky, L
Lafer, MM
KuKuruga, MA
Silberstein, E
Cehan, N
Taylor, DR
AF Ulitzky, Laura
Lafer, Manuel M.
KuKuruga, Mark A.
Silberstein, Erica
Cehan, Nicoleta
Taylor, Deborah R.
TI A New Signaling Pathway for HCV Inhibition by Estrogen: GPR30 Activation
Leads to Cleavage of Occludin by MMP-9
SO PLOS ONE
LA English
DT Article
ID HEPATITIS-C VIRUS; TIGHT JUNCTIONAL RESISTANCE; PROTEIN-COUPLED
RECEPTOR; HEPATOMA-CELLS; BREAST-CANCER; ENTRY; POLARIZATION; INFECTION;
DISEASE; PROGRESSION
AB Poor outcome in response to hepatitis C virus, including higher viral load, hepatocellular carcinoma and cirrhosis, is more associated with men and postmenopausal women than with premenopausal women and women receiving hormone replacement therapy, suggesting that a-estradiol plays an innate role in preventing viral infection and liver disease. Consequently, most research in the field has concluded that estrogen affects HCV replication through viral interactions with estrogen receptor-a. Previously, estrogen-like antagonists, including Tamoxifen, were shown to reduce HCV RNA production and prevent viral entry, although the authors did not identify host factors involved. Estrogen can act alternatively through the membrane-bound G-protein-coupled estrogen receptor, GPR30. Here, human hepatoma Huh7.5 cells were infected with HCV J6/JFH-1 and treated with estrogen or Tamoxifen, resulting in a marked decrease in detectable virus. The effect was mimicked by G1, a GPR30-specific agonist, and was reversed by the GPR30-specific antagonist, G15. While previous studies have demonstrated that estrogen down-regulated occludin in cervical cancer cells, its action on liver cells was unknown. Occludin is a tight junction protein and HCV receptor and here we report that activation and cellular export of MMP-9 led to the cleavage of occludin upon estrogen treatment of liver cells. This is the first report of the cleavage of an HCV receptor in response to estrogen. We also identify the occludin cleavage site in extracellular Domain D; the motif required for HCV entry and spread. This pathway gives new insight into a novel innate antiviral pathway and the suboptimal environment that estrogen provides for the proliferation of the virus. It may also explain the disparate host-virus responses to HCV demonstrated by the two sexes. Moreover, these data suggest that hormone replacement therapy may have beneficial antiviral enhancement properties for HCV-infected postmenopausal women and show promise for new antiviral treatments for both men and women.
C1 [Ulitzky, Laura; Lafer, Manuel M.; KuKuruga, Mark A.; Silberstein, Erica; Cehan, Nicoleta; Taylor, Deborah R.] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
RP Taylor, DR (reprint author), US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
EM Deborah.Taylor@fda.hhs.gov
FU Office of Women's Health, U.S. Food and Drug Administration
FX This work was funded by the Office of Women's Health, U.S. Food and Drug
Administration.; We gratefully acknowledge funding by the Office of
Women's Health, U.S. Food and Drug Administration. We thank C.M. Rice
for virus and cells and special thanks to German Anez for helpful
discussions and invaluable input. The findings and conclusions in this
article have not been formally disseminated by the Food and Drug
Administration and should not be construed to represent any Agency
determination or policy.
NR 48
TC 3
Z9 3
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 5
PY 2016
VL 11
IS 1
AR e0145212
DI 10.1371/journal.pone.0145212
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA4VZ
UT WOS:000367801400027
PM 26731262
ER
PT J
AU Yang, MB
Ruan, JQ
Fu, PP
Lin, G
AF Yang, Mengbi
Ruan, Jianqing
Fu, Peter P.
Lin, Ge
TI Cytotoxicity of pyrrolizidine alkaloid in human hepatic parenchymal and
sinusoidal endothelial cells: Firm evidence for the reactive metabolites
mediated pyrrolizidine alkaloid-induced hepatotoxicity
SO CHEMICO-BIOLOGICAL INTERACTIONS
LA English
DT Article
DE Pyrrolizidine alkaloids; Hepatotoxicity; Metabolic activation; Reactive
metabolites; Hepatic sinusoidal endothelial cell damage; Pyrrole-protein
adducts
ID OBSTRUCTION SYNDROME; VENOOCCLUSIVE DISEASE; HUMAN HEPATOCYTES; RAT
HEPATOCYTES; LIVER-DISEASE; MONOCROTALINE; DEHYDRORETRONECINE;
GLUTATHIONE; TOXICITY; ACTIVATION
AB Pyrrolizidine alkaloids (PAs) widely distribute in plants and can cause hepatic sinusoidal obstruction syndrome (HSOS), which typically presents as a primary sinusoidal endothelial cell damage. It is well-recognized that after ingestion, PAs undergo hepatic cytochromes P450 (CYPs)-mediated metabolic activation to generate dehydropyrrolizidine alkaloids (DHPAs), which are hydrolyzed to dehydroretronecine (DHR). DHPAs and DHR are reactive metabolites having same core pyrrole moiety, and can bind proteins to form pyrrole-protein adducts, which are believed as the primary cause for PA-induced HSOS. However, to date, the direct evidences supporting the toxicity of DHPAs and DHR in the liver, in particular in the sinusoidal endothelial cells, are lacking. Using human hepatic sinusoidal endothelial cells (HSEC) and HepG2 (representing hepatic parenchymal cells), cells that lack CYPs activity, this study determined the direct cytotoxicity of dehydromonocrotaline, a representative DHPA, and DHR, but no cytotoxicity of the intact PA (monocrotaline) in both cell lines, confirming that reactive metabolites mediate PA intoxication. Comparing with HepG2, HSEC had significantly lower basal glutathione (GSH) level, and was significantly more susceptible to the reactive metabolites with severer GSH depletion and pyrrole-protein adducts formation. The toxic potency of two reactive metabolites was also compared. DHPA was more reactive than DHR, leading to severer toxicity. In conclusion, our results unambiguously provided the first direct evidence for the critical role of DHPA and DHR in the reactive metabolites-mediated PA-induced hepatotoxicity, which occurs predominantly in HSEC due to severe GSH depletion and the significant formation of pyrrole-protein adducts in HSEC. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Yang, Mengbi; Ruan, Jianqing; Lin, Ge] Chinese Univ Hong Kong, Sch Biomed Sci, Fac Med, Hong Kong, Hong Kong, Peoples R China.
[Yang, Mengbi; Ruan, Jianqing; Lin, Ge] Chinese Acad Sci, Joint Res Lab Promoting Globalizat Tradit Chinese, Beijing 100864, Peoples R China.
[Fu, Peter P.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Lin, G (reprint author), Chinese Univ Hong Kong, Sch Biomed Sci, Fac Med, Hong Kong, Hong Kong, Peoples R China.
EM linge@cuhk.edu.hk
FU Research Grant Council of Hong Kong SAR [469712, 471013, 2140898];
Chinese University of Hong Kong [4054134, 4054215]; CUHK School of
Biomedical Sciencese-Seed Fund for Joint Establishments
FX The present studies were supported by Research Grant Council of Hong
Kong SAR (GRF Grants, Project No.: 469712, 471013 and 2140898), The
Chinese University of Hong Kong (Direct Grants: 4054134 and 4054215),
and CUHK School of Biomedical Sciencese-Seed Fund for Joint
Establishments. This article is not an official U.S. Food and Drug
Administration (FDA) guidance or policy statement. No official support
or endorsement by the U.S. FDA is intended or should be inferred. The
authors declare no competing financial interest.
NR 53
TC 1
Z9 2
U1 6
U2 21
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0009-2797
EI 1872-7786
J9 CHEM-BIOL INTERACT
JI Chem.-Biol. Interact.
PD JAN 5
PY 2016
VL 243
BP 119
EP 126
DI 10.1016/j.cbi.2015.09.011
PG 8
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
GA CZ8QP
UT WOS:000367364500013
PM 26365561
ER
PT J
AU Lambertini, E
Buchanan, RL
Narrod, C
Ford, RM
Baker, RC
Pradhan, AK
AF Lambertini, Elisabetta
Buchanan, Robert L.
Narrod, Clare
Ford, Randall M.
Baker, Robert C.
Pradhan, Abani K.
TI Quantitative assessment of human and pet exposure to Salmonella
associated with dry pet foods
SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY
LA English
DT Article
DE Dry pet food; Low moisture; Zoonotic pathogens; Risk assessment;
Household handling
ID UNITED-STATES; CROSS-CONTAMINATION; LISTERIA-MONOCYTOGENES; DOG FOOD;
ANTIMICROBIAL SUSCEPTIBILITY; FOODBORNE ILLNESS; HUMAN HEALTH; CAT FOOD;
OUTBREAK; INFECTIONS
AB Recent Salmonella outbreaks associated with dry pet foods and treats highlight the importance of these foods as previously overlooked exposure vehicles for both pets and humans. In the last decade efforts have been made to raise the safety of this class of products, for instance by upgrading production equipment, cleaning protocols, and finished product testing. However, no comprehensive or quantitative risk profile is available for pet foods, thus limiting the ability to establish safety standards and assess the effectiveness of current and proposed Salmonella control measures. This study sought to develop an ingredients-to-consumer quantitative microbial exposure assessment model to: 1) estimate pet and human exposure to Salmonella via dry pet food, and 2) assess the impact of industry and household-level mitigation strategies on exposure. Data on prevalence and concentration of Salmonella in pet food ingredients, production process parameters, bacterial ecology, and contact transfer in the household were obtained through literature review, industry data, and targeted research. A probabilistic Monte Carlo modeling framework was developed to simulate the production process and basic household exposure routes. Under the range of assumptions adopted in this model, human exposure due to handling pet food is null to minimal if contamination occurs exclusively before extrusion. Exposure increases considerably if recontamination occurs post-extrusion during coating with fat, although mean ingested doses remain modest even at high fat contamination levels, due to the low percent of fat in the finished product. Exposure is highly variable, with the distribution of doses ingested by adult pet owners spanning 3 Log CFU per exposure event. Child exposure due to ingestion of 1 g of pet food leads to significantly higher doses than adult doses associated with handling the food. Recontamination after extrusion and coating, e.g., via dust or equipment surfaces, may also lead to exposure due to the absence of pathogen reduction steps after extrusion or at consumer households. Exposure is potentially highest when Salmonella is transferred to human food that is left at growth-promoting conditions. This model can be applied to evaluate the impact of alternative Salmonella control measures during production, risk communication to consumers, and regulatory standards. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Lambertini, Elisabetta; Buchanan, Robert L.; Pradhan, Abani K.] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA.
[Lambertini, Elisabetta; Buchanan, Robert L.; Pradhan, Abani K.] Univ Maryland, Ctr Food Safety & Secur Syst, College Pk, MD 20742 USA.
[Narrod, Clare] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA.
[Ford, Randall M.] Mars Petcare US, Franklin, TN 37067 USA.
[Baker, Robert C.] Mars Global Food Safety Ctr, Beijing 101407, Peoples R China.
RP Pradhan, AK (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA.
EM akp@umd.edu
FU MARS Petcare
FX This study was funded by MARS Petcare. The authors wish to thank the
team of students who assisted in the laboratory experiments on
Salmonella decline and growth on pet food, in particular Ruth Oni,
Huilin Cao, Miao Guo, Abhinav Mishra, Lind Wang, Xinyue Wang, Kathy Lou,
Dan Li, and Yu Wang.
NR 63
TC 1
Z9 1
U1 10
U2 55
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1605
EI 1879-3460
J9 INT J FOOD MICROBIOL
JI Int. J. Food Microbiol.
PD JAN 4
PY 2016
VL 216
BP 79
EP 90
DI 10.1016/j.ijfoodmicro.2015.09.005
PG 12
WC Food Science & Technology; Microbiology
SC Food Science & Technology; Microbiology
GA CW3LM
UT WOS:000364893800010
PM 26414858
ER
PT J
AU Koti, KM
AF Koti, Kallappa M.
TI New Generalized p-Value Approach for Noninferiority Analysis
SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH
LA English
DT Article
DE Sample size.; Probability value; Beta distribution; Behrens-Fisher
problem; Noncentrality parameter
ID NON-INFERIORITY; TRIALS; CURVES
AB The underlying statistical exercise in some noninferiority studies is to test a composite null hypothesis of a nonzero difference in the means of two normally distributed populations. These noninferiority studies are often analyzed under equal variances assumption. Unequal variances frequently occur in practice. In this article, we propose a noncentral t-distribution-based generalized test for proving noninferiority in the presence of unequal variances. We provide a simple SAS IML code to calculate the new generalized p-value. We compare the new generalized p-value with that of the Student's central t-distribution-based Tsui-Weerahandi generalized test. We conclude that Tsui-Weerahandi generalized test is conservative.
C1 [Koti, Kallappa M.] US FDA, Div Biometr 5, 10903 New Hampshire Ave,HFD 711,Bldg 21, Silver Spring, MD 20993 USA.
RP Koti, KM (reprint author), US FDA, Div Biometr 5, 10903 New Hampshire Ave,HFD 711,Bldg 21, Silver Spring, MD 20993 USA.
EM Kallappa.Koti@fda.hhs.gov
NR 14
TC 0
Z9 0
U1 1
U2 2
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 1946-6315
J9 STAT BIOPHARM RES
JI Stat. Biopharm. Res.
PD JAN 2
PY 2016
VL 8
IS 1
BP 35
EP 39
DI 10.1080/19466315.2015.1093958
PG 5
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA DH5QY
UT WOS:000372848100004
ER
PT J
AU Weaver, J
Ohlssen, D
Li, JX
AF Weaver, Jerry
Ohlssen, David
Li, Judy X.
TI Strategies on Using Prior Information When Assessing Adverse Events
SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH
LA English
DT Article
DE Conjugate prior; Prior-data conflict; Bayesian methods;
Meta-analytic-predictive prior; Robust mixture prior.
ID CLINICAL-TRIALS; HISTORICAL INFORMATION; DRUG SAFETY; MODELS
AB Assessing safety in drug development naturally incorporates an accumulation of knowledge as we progress from one study to another in a clinical development program. Ideally, it is the early clinical trial data that give us the greatest opportunity to leverage relevant historical information into the design and analysis of later phase clinical trials. While Bayesian methods would appear to provide an ideal framework for assessing safety in this context, concerns regarding the formulation and prespecification of a prior have limited their use in practice. More specifically, when information from previous studies is used to form a prior, an implicit assumption of exchangeability is made. However, the possibility of nonexchangeability, which could lead to conflict between prior and the data, cannot be ruled out. Based on these challenges, in this article we outline a number of strategies based on using simple Bayesian methods to assess safety concerns related to a prespecified adverse event. Three approaches to forming a prior distribution will be examined: (i) a single informative conjugate prior; (ii) a meta-analytic-predictive prior (MAP), which comprises of a mixture of conjugate priors; and (iii) a robust mixture prior, involving a combination of either the single conjugate prior or MAP with a noninformative prior. In the final case, when prior-data conflict arises between the historical informative prior and the data collected from the concurrent study, the addition of a noninformative prior serves as an automatic corrective feature. These methods will be illustrated with a motivating example involving the development of a new drug/delivery device for the treatment of agitation in schizophrenia. In addition, a simulation study will examine the performance of each approach to prior specification.
C1 [Weaver, Jerry; Ohlssen, David] Novartis Pharmaceut, E Hanover, NJ 07936 USA.
[Li, Judy X.] US FDA, Silver Spring, MD 20993 USA.
RP Weaver, J; Ohlssen, D (reprint author), Novartis Pharmaceut, E Hanover, NJ 07936 USA.; Li, JX (reprint author), US FDA, Silver Spring, MD 20993 USA.
EM jerry.weaver@novartis.com; david.ohlssen@novartis.com;
judy.li@fda.hhs.gov
NR 13
TC 2
Z9 2
U1 1
U2 2
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 1946-6315
J9 STAT BIOPHARM RES
JI Stat. Biopharm. Res.
PD JAN 2
PY 2016
VL 8
IS 1
BP 106
EP 115
DI 10.1080/19466315.2015.1067252
PG 10
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA DH5QY
UT WOS:000372848100010
ER
PT J
AU Bot, A
Bailey, C
Brumeanu, T
Casares, S
Kuppuswamy, K
Zaghouani, H
AF Bot, Adrian
Bailey, Celeste
Brumeanu, Teodor
Casares, Sofia
Kuppuswamy, Kasturi
Zaghouani, Habib
TI Constantin A. Bona, M.D., Ph.D. OBITUARY
SO INTERNATIONAL REVIEWS OF IMMUNOLOGY
LA English
DT Biographical-Item
C1 [Bot, Adrian] Kite Pharma Inc, Int Reviews Immunol, 2225 Colorado Ave, Santa Monica, CA 90404 USA.
[Bot, Adrian] Kite Pharma Inc, Translat Sci, 2225 Colorado Ave, Santa Monica, CA 90404 USA.
[Bailey, Celeste] AMCR Inst, Escondido, CA USA.
[Bailey, Celeste] Natl Univ, San Diego, CA USA.
[Brumeanu, Teodor] Uniformed Serv Univ Hlth Sci, Dept Med Mol & Cell Biol, Bethesda, MD 20814 USA.
[Casares, Sofia] Walter Reed Army Inst Res, US Mil Malaria Vaccine Program, Preclin Res, Naval Med Res Center, Silver Spring, MD USA.
[Kuppuswamy, Kasturi] US FDA, US Dept HHS, Washington, DC 20204 USA.
[Zaghouani, Habib] Univ Missouri, Mol Microbiol & Immunol, Columbia, MO USA.
RP Bot, A (reprint author), Kite Pharma Inc, Int Reviews Immunol, 2225 Colorado Ave, Santa Monica, CA 90404 USA.; Bot, A (reprint author), Kite Pharma Inc, Translat Sci, 2225 Colorado Ave, Santa Monica, CA 90404 USA.
EM abot@kitepharma.com
NR 1
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0883-0185
EI 1563-5244
J9 INT REV IMMUNOL
JI Int. Rev. Immunol.
PD JAN 2
PY 2016
VL 35
IS 1
BP 1
EP 3
DI 10.3109/08830185.2016.1139991
PG 3
WC Immunology
SC Immunology
GA DG5EN
UT WOS:000372098300001
PM 26959800
ER
PT J
AU He, XB
Xia, QS
Ma, L
Fu, PP
AF He, Xiaobo
Xia, Qingsu
Ma, Liang
Fu, Peter P.
TI 7-cysteine-pyrrole conjugate: A new potential DNA reactive metabolite of
pyrrolizidine alkaloids
SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL
CARCINOGENESIS & ECOTOXICOLOGY REVIEWS
LA English
DT Review
DE DNA adduct formation; metabolic activation; Pyrrolizidine alkaloid;
7-cysteine-DHP adducts
ID ALCOHOL GLUTATHIONE CONJUGATE; FORMATION IN-VIVO; ADDUCT FORMATION;
MICROSOMAL FORMATION; DIETARY-SUPPLEMENTS; N-OXIDES; ACTIVATION; LIVER;
MONOCROTALINE; TUMORIGENICITY
AB Pyrrolizidine alkaloids (PAs) require metabolic activation to exert cytotoxicity, genotoxicity, and tumorigenicity. We previously reported that (+/-)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts are responsible for PA-induced liver tumor formation in rats. In this study, we determined that metabolism of riddelliine and monocrotaline by human or rat liver microsomes produced 7-cysteine-DHP and DHP. The metabolism of 7-glutathionyl-DHP by human and rat liver microsomes also generated 7-cysteine-DHP. Further, reaction of 7-cysteine-DHP with calf thymus DNA in aqueous solution yielded the described DHP-derived DNA adducts. This study represents the first report that 7-cysteine-DHP is a new PA metabolite that can lead to DNA adduct formation.
C1 [He, Xiaobo; Xia, Qingsu; Ma, Liang; Fu, Peter P.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Fu, PP (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
EM peter.fu@fda.hhs.gov
NR 33
TC 2
Z9 2
U1 2
U2 7
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1059-0501
EI 1532-4095
J9 J ENVIRON SCI HEAL C
JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev.
PD JAN 2
PY 2016
VL 34
IS 1
BP 57
EP 76
DI 10.1080/10590501.2015.1135593
PG 20
WC Oncology; Environmental Sciences; Toxicology
SC Oncology; Environmental Sciences & Ecology; Toxicology
GA DG0HZ
UT WOS:000371747200003
PM 26761716
ER
PT J
AU Campbell, G
Yue, LQ
AF Campbell, Gregory
Yue, Lilly Q.
TI Statistical innovations in the medical device world sparked by the FDA
SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS
LA English
DT Article
DE Adaptive designs; Bayesian statistics; clinical trials; diagnostic test
evaluation; missing data; propensity score; quantitative benefit-risk
ID PROPENSITY SCORE; REGULATORY ISSUES; CLINICAL-TRIALS; MISSING DATA;
DESIGN; PREFERENCES; CHALLENGES; EXPERIENCE; ACCURACY; RISKS
AB The world of medical devices while highly diverse is extremely innovative, and this facilitates the adoption of innovative statistical techniques. Statisticians in the Center for Devices and Radiological Health (CDRH) at the Food and Drug Administration (FDA) have provided leadership in implementing statistical innovations. The innovations discussed include: the incorporation of Bayesian methods in clinical trials, adaptive designs, the use and development of propensity score methodology in the design and analysis of non-randomized observational studies, the use of tipping-point analysis for missing data, techniques for diagnostic test evaluation, bridging studies for companion diagnostic tests, quantitative benefit-risk decisions, and patient preference studies.
C1 [Campbell, Gregory; Yue, Lilly Q.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
RP Yue, LQ (reprint author), US FDA, CDRH, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM lilly.yue@fda.hhs.gov
NR 49
TC 1
Z9 1
U1 1
U2 3
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1054-3406
EI 1520-5711
J9 J BIOPHARM STAT
JI J. Biopharm. Stat.
PD JAN 2
PY 2016
VL 26
IS 1
SI SI
BP 3
EP 16
DI 10.1080/10543406.2015.1092037
PG 14
WC Pharmacology & Pharmacy; Statistics & Probability
SC Pharmacology & Pharmacy; Mathematics
GA DB7VR
UT WOS:000368725300002
PM 26372890
ER
PT J
AU Chakravarty, AG
Izem, R
Keeton, S
Kim, CY
Levenson, MS
Soukup, M
AF Chakravarty, Aloka G.
Izem, Rima
Keeton, Stephine
Kim, Clara Y.
Levenson, Mark S.
Soukup, Mat
TI The role of quantitative safety evaluation in regulatory decision making
of drugs
SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS
LA English
DT Article
DE Evaluation of risk from extended; long-acting opioids; large safety
outcome trials; meta-analysis for safety evaluation; post-marketing
requirements; quantitative safety evaluation; the sentinel initiative
ID RANDOMIZED CONTROLLED-TRIALS; MORTALITY RISKS; MYOCARDIAL-INFARCTION;
PROPENSITY SCORE; US FOOD; ANTIDEPRESSANTS; METAANALYSIS; SUICIDALITY;
DABIGATRAN; DISEASE
AB Evaluation of safety is a critical component of drug review at the US Food and Drug Administration (FDA). Statisticians are playing an increasingly visible role in quantitative safety evaluation and regulatory decision-making. This article reviews the history and the recent events relating to quantitative drug safety evaluation at the FDA. The article then focuses on five active areas of quantitative drug safety evaluation and the role Division of Biometrics VII (DBVII) plays in these areas, namely meta-analysis for safety evaluation, large safety outcome trials, post-marketing requirements (PMRs), the Sentinel Initiative, and the evaluation of risk from extended/long-acting opioids. This article will focus chiefly on developments related to quantitative drug safety evaluation and not on the many additional developments in drug safety in general.
C1 [Chakravarty, Aloka G.; Izem, Rima; Keeton, Stephine; Kim, Clara Y.; Levenson, Mark S.; Soukup, Mat] US FDA, Ctr Drug Evaluat & Res, Div Biometr 7, Off Biostat, 10903 New Hampshire Ave,Bldg 21 Room 3514, Silver Spring, MD 20993 USA.
RP Chakravarty, AG (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Biometr 7, Off Biostat, 10903 New Hampshire Ave,Bldg 21 Room 3514, Silver Spring, MD 20993 USA.
EM aloka.chakravarty@fda.hhs.gov
NR 42
TC 0
Z9 0
U1 0
U2 2
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1054-3406
EI 1520-5711
J9 J BIOPHARM STAT
JI J. Biopharm. Stat.
PD JAN 2
PY 2016
VL 26
IS 1
SI SI
BP 17
EP 29
DI 10.1080/10543406.2015.1092026
PG 13
WC Pharmacology & Pharmacy; Statistics & Probability
SC Pharmacology & Pharmacy; Mathematics
GA DB7VR
UT WOS:000368725300003
PM 26372792
ER
PT J
AU McEvoy, BW
AF McEvoy, Bradley W.
TI Missing data in clinical trials for weight management
SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS
LA English
DT Article
DE Estimands; missing data; sensitivity analyses
AB In 2014, the US FDA approved liraglutide for weight management. The statistical review of the application presented various challenges related to the handling of missing data. The ability of the drug to cause weight loss was not in question. The challenge centered on obtaining a reliable estimate of the intention-to-treat effect to support the risk-benefit evaluation. Subjects in the trials that stopped treatment prior to the endpoint were encouraged to attend the primary endpoint visit. Data from the subjects that returned for a primary efficacy assessment played a significant role in the statistical review. They were used to illustrate shortcomings of the applicant's primary efficacy analysis and sensitivity analyses. They were also used in the FDA analyses to address missing data. The goal of this article is to illustrate challenges and considerations associated with the handling of missing data in clinical trials.
C1 [McEvoy, Bradley W.] US FDA, Ctr Drug Evaluat & Res, Off Biostat, Div Biometr 2, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
RP McEvoy, BW (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Biostat, Div Biometr 2, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM bradley.mcevoy@fda.hhs.gov
NR 14
TC 1
Z9 1
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1054-3406
EI 1520-5711
J9 J BIOPHARM STAT
JI J. Biopharm. Stat.
PD JAN 2
PY 2016
VL 26
IS 1
SI SI
BP 30
EP 36
DI 10.1080/10543406.2015.1094814
PG 7
WC Pharmacology & Pharmacy; Statistics & Probability
SC Pharmacology & Pharmacy; Mathematics
GA DB7VR
UT WOS:000368725300004
PM 26418188
ER
PT J
AU Hung, HMJ
Wang, SJ
Yang, PL
Jin, K
Lawrence, J
Kordzakhia, G
Massie, T
AF Hung, H. M. James
Wang, Sue-Jane
Yang, Peiling
Jin, Kun
Lawrence, John
Kordzakhia, George
Massie, Tristan
TI Statistical challenges in a regulatory review of cardiovascular and CNS
clinical trials
SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS
LA English
DT Article
DE Adaptive design; adaptive selection; adaptive statistical information;
branching decision rule; multiplicity; type I error
ID MULTIPLE END-POINTS; CONFIDENCE-INTERVALS; SAMPLE-SIZE; SEQUENTIAL
DESIGN
AB There are several challenging statistical problems identified in the regulatory review of large cardiovascular (CV) clinical outcome trials and central nervous system (CNS) trials. The problems can be common or distinct due to disease characteristics and the differences in trial design elements such as endpoints, trial duration, and trial size. In schizophrenia trials, heavy missing data is a big problem. In Alzheimer trials, the endpoints for assessing symptoms and the endpoints for assessing disease progression are essentially the same; it is difficult to construct a good trial design to evaluate a test drug for its ability to slow the disease progression. In CV trials, reliance on a composite endpoint with low event rate makes the trial size so large that it is infeasible to study multiple doses necessary to find the right dose for study patients. These are just a few typical problems. In the past decade, adaptive designs were increasingly used in these disease areas and some challenges occur with respect to that use. Based on our review experiences, group sequential designs (GSDs) have borne many successful stories in CV trials and are also increasingly used for developing treatments targeting CNS diseases. There is also a growing trend of using more advanced unblinded adaptive designs for producing efficacy evidence. Many statistical challenges with these kinds of adaptive designs have been identified through our experiences with the review of regulatory applications and are shared in this article.
C1 [Hung, H. M. James; Yang, Peiling; Jin, Kun; Lawrence, John; Kordzakhia, George; Massie, Tristan] US FDA, Off Translat Sci, Ctr Drug Evaluat & Res, Off Biostat,Div Biometr 1, Silver Spring, MD USA.
[Wang, Sue-Jane] US FDA, Ctr Drug Evaluat & Res, Off Biostat, Off Translat Sci, Silver Spring, MD USA.
RP Hung, HMJ (reprint author), US FDA, OB OTS CDER, Div Biometr 1, 10903 New Hampshire Ave,Bldg 21,Room 4616, Silver Spring, MD 20993 USA.
EM hsienming.hung@fda.hhs.gov
NR 24
TC 0
Z9 0
U1 0
U2 2
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1054-3406
EI 1520-5711
J9 J BIOPHARM STAT
JI J. Biopharm. Stat.
PD JAN 2
PY 2016
VL 26
IS 1
SI SI
BP 37
EP 43
DI 10.1080/10543406.2015.1092025
PG 7
WC Pharmacology & Pharmacy; Statistics & Probability
SC Pharmacology & Pharmacy; Mathematics
GA DB7VR
UT WOS:000368725300005
PM 26366624
ER
PT J
AU Wu, PS
Lin, M
Chow, SC
AF Wu, Pei-Shien
Lin, Min
Chow, Shein-Chung
TI On sample size estimation and re-estimation adjusting for variability in
confirmatory trials
SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS
LA English
DT Article
DE Achieving conditional power; controlling variability; maintaining effect
size; reproducibility probability
ID CLINICAL-TRIALS; INTERNAL PILOT; T-TEST
AB Sample size estimation (SSE) is an important issue in the planning of clinical studies. While larger studies are likely to have sufficient power, it may be unethical to expose more patients than necessary to answer a scientific question. Budget considerations may also cause one to limit the study to an adequate size to answer the question at hand. Typically at the planning stage, a statistically based justification for sample size is provided. An effective sample size is usually planned under a pre-specified type I error rate, a desired power under a particular alternative and variability associated with the observations recorded. The nuisance parameter such as the variance is unknown in practice. Thus, information from a preliminary pilot study is often used to estimate the variance. However, calculating the sample size based on the estimated nuisance parameter may not be stable. Sample size re-estimation (SSR) at the interim analysis may provide an opportunity to re-evaluate the uncertainties using accrued data and continue the trial with an updated sample size. This article evaluates a proposed SSR method based on controlling the variability of nuisance parameter. A numerical study is used to assess the performance of proposed method with respect to the control of type I error. The proposed method and concepts could be extended to SSR approaches with respect to other criteria, such as maintaining effect size, achieving conditional power, and reaching a desired reproducibility probability.
C1 [Wu, Pei-Shien; Chow, Shein-Chung] Duke Univ, Sch Med, Dept Biostat & Bioinformat, Durham, NC USA.
[Wu, Pei-Shien; Lin, Min] US FDA, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
RP Lin, M (reprint author), US FDA, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM min.lin@fda.hhs.gov
NR 14
TC 0
Z9 0
U1 1
U2 3
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1054-3406
EI 1520-5711
J9 J BIOPHARM STAT
JI J. Biopharm. Stat.
PD JAN 2
PY 2016
VL 26
IS 1
SI SI
BP 44
EP 54
DI 10.1080/10543406.2015.1092031
PG 11
WC Pharmacology & Pharmacy; Statistics & Probability
SC Pharmacology & Pharmacy; Mathematics
GA DB7VR
UT WOS:000368725300006
PM 26378970
ER
PT J
AU Ivanova, A
Zhang, ZW
Thompson, L
Yang, Y
Kotz, RM
Fang, X
AF Ivanova, Anastasia
Zhang, Zhiwei
Thompson, Laura
Yang, Ying
Kotz, Richard M.
Fang, Xin
TI Can sequential parallel comparison design and two-way enriched design be
useful in medical device clinical trials?
SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS
LA English
DT Article
DE Medical device; placebo response; sequential parallel comparison design;
SPCD; TED; two-way enriched design
ID PLACEBO-RESPONSE; DOUBLE-BLIND; MAJOR DEPRESSION; STIMULATION;
STATISTICS
AB Sequential parallel comparison design (SPCD) was proposed for trials with high placebo response. In the first stage of SPCD subjects are randomized between placebo and active treatment. In the second stage placebo nonresponders are re-randomized between placebo and active treatment. Data from the population of all comers and the subpopulations of placebo nonresponders then combined to yield a single p-value for treatment comparison. Two-way enriched design (TED) is an extension of SPCD where active treatment responders are also re-randomized between placebo and active treatment in Stage 2. This article investigates the potential uses of SPCD and TED in medical device trials.
C1 [Ivanova, Anastasia] Univ N Carolina, Dept Biostat, CB 7420, Chapel Hill, NC 27599 USA.
[Zhang, Zhiwei; Thompson, Laura; Yang, Ying; Kotz, Richard M.; Fang, Xin] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Ivanova, A (reprint author), Univ N Carolina, Dept Biostat, CB 7420, Chapel Hill, NC 27599 USA.
EM aivanova@bios.unc.edu
NR 20
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1054-3406
EI 1520-5711
J9 J BIOPHARM STAT
JI J. Biopharm. Stat.
PD JAN 2
PY 2016
VL 26
IS 1
SI SI
BP 167
EP 177
DI 10.1080/10543406.2015.1092028
PG 11
WC Pharmacology & Pharmacy; Statistics & Probability
SC Pharmacology & Pharmacy; Mathematics
GA DB7VR
UT WOS:000368725300013
PM 26368863
ER
PT J
AU Duncan, R
Kourout, M
Grigorenko, E
Fisher, C
Dong, M
AF Duncan, Robert
Kourout, Moussa
Grigorenko, Elena
Fisher, Carolyn
Dong, Ming
TI Advances in multiplex nucleic acid diagnostics for blood-borne
pathogens: promises and pitfalls
SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
LA English
DT Review
DE multiplex diagnostics; nucleic acid tests; blood-borne; pathogen
ID MEDIATED ISOTHERMAL AMPLIFICATION; POLYMERASE-CHAIN-REACTION;
RESPIRATORY-TRACT INFECTIONS; IONIZATION MASS-SPECTROMETRY; T2
MAGNETIC-RESONANCE; REAL-TIME; RAPID DIAGNOSIS; DENGUE VIRUS;
ANTIMICROBIAL THERAPY; HOSPITALIZED-PATIENTS
AB The large number of blood-borne viruses, bacteria and parasites currently of concern, as well as many newly emerging pathogens, presents a daunting challenge to protection of the safety of blood for transfusion and diagnosing infectious diseases. Focusing on nucleic acid diagnostic tests, multiplex devices are coming into use with many more in various developmental stages that promise to offer solutions to the clinical need. The characteristics, advantages and disadvantages of platforms in clinical use and at the research and development stage are examined here. The presence of multiple assays and associated reagents operating simultaneously on one platform, implementation in traditional clinical laboratories and regulatory review will present special challenges. Fortunately, clinical laboratories have made dramatic technical progress in the last two decades and regulatory agencies have publicly expressed support for development of multiplex devices.
C1 [Duncan, Robert; Kourout, Moussa; Fisher, Carolyn; Dong, Ming] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
[Grigorenko, Elena] Diatherix Labs LLC, Huntsville, AL 35806 USA.
RP Duncan, R (reprint author), US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
EM Robert.duncan@fda.hhs.gov
NR 102
TC 0
Z9 0
U1 2
U2 12
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1473-7159
EI 1744-8352
J9 EXPERT REV MOL DIAGN
JI Expert Rev. Mol. Diagn.
PD JAN 2
PY 2016
VL 16
IS 1
BP 83
EP 95
DI 10.1586/14737159.2016.1112272
PG 13
WC Pathology
SC Pathology
GA DB3XG
UT WOS:000368446200001
PM 26581018
ER
PT J
AU Volpe, DA
AF Volpe, Donna A.
TI Transporter assays as useful in vitro tools in drug discoveryand
development
SO EXPERT OPINION ON DRUG DISCOVERY
LA English
DT Review
DE Drug transporters; efflux; in vitro; uptake
ID SANDWICH-CULTURED HEPATOCYTES; CANCER RESISTANCE PROTEIN; P-GP
INHIBITION; SUPPORT REGULATORY SUBMISSIONS; ORGANIC CATION TRANSPORTER;
HUMAN INTESTINAL-MUCOSA; PROXIMAL TUBULAR CELLS; SPECIES-DIFFERENCES;
EFFLUX TRANSPORTERS; CACO-2 CELLS
AB Introduction: Drug transporters are transmembrane proteins that facilitate the transfer of substances in and out of cells and play a substantial role in drug absorption, distribution and elimination. During the drug discovery and development phases, in vitro assays are important tools to identify substrates and inhibitors of transporters.Areas covered: This article provides an overview of in vitro transporter assays, discussing their advantages, limitations, and sources of variability. Membrane-based assays take advantage of the location of efflux transporters for measurements of drug interactions. Cell-based systems are functional transporter assays that measure the passage of drugs across cell membranes and transporter proteins.Expert opinion: Use of optimized and validated in vitro transporter assays during drug discovery and development leads to a greater confidence in their results in determining whether a new compound is a substrate or inhibitor. The concept of transporter method suitability provides a general scheme to improve predictability and reduce variability of the in vitro assays by incorporating assay validation, acceptance criteria, and probe substrates and inhibitors. Such a scheme can potentially improve assay reproducibility and allow in vitro transporter assays to aid in defining a test compound as a substrate or inhibitor of efflux and uptake transporters.
C1 [Volpe, Donna A.] US FDA, Silver Spring, MD 20903 USA.
RP Volpe, DA (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
EM donna.volpe@fda.hhs.gov
NR 113
TC 0
Z9 0
U1 7
U2 17
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1746-0441
EI 1746-045X
J9 EXPERT OPIN DRUG DIS
JI Expert. Opin. Drug Discov.
PD JAN 2
PY 2016
VL 11
IS 1
BP 91
EP 103
DI 10.1517/17460441.2016.1101064
PG 13
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DA7ZQ
UT WOS:000368024500002
PM 26512742
ER
PT J
AU Sy, SKB
Zhuang, LN
Derendorf, H
AF Sy, Sherwin K. B.
Zhuang, Luning
Derendorf, Hartmut
TI Pharmacokinetics and pharmacodynamics in antibiotic dose optimization
SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
LA English
DT Review
DE antibiotics; in vitro models; PK-PD modeling; translational research
ID CRITICALLY-ILL PATIENTS; LUNG INFECTION MODELS; COMMUNITY-ACQUIRED
PNEUMONIA; SKIN-STRUCTURE INFECTIONS; PARA-AMINOSALICYLIC ACID; MUTANT
SELECTION WINDOW; STAGE RENAL-DISEASE; IN-VITRO MODEL;
PSEUDOMONAS-AERUGINOSA; BETA-LACTAMASE
AB Introduction: Identifying the optimized dosing regimen and algorithm is critical in the development of antibiotics. Suboptimal regimens and inappropriate choice of drug give rise to drug-resistant bacteria which have limited the therapeutic utility of many commercially available antimicrobial agents. Strategies to optimize therapy of antimicrobial candidates to speed up the development process are urgently needed.Areas covered: We examined pharmacokinetics and pharmacodynamics of antimicrobial agents with modeling and simulation approaches. The approach that is based on minimum inhibitory concentration to evaluate antimicrobial dosing strategy is widely utilized in drug development. The modeling approach utilizing information from time-kill kinetic studies is a tool that can provide more information on the time-course of bacterial response to a particular dosing regimen. Animal studies of dosing regimens that mimic human pharmacokinetics are another option to evaluate antimicrobial efficacy. Empirical, semi-mechanistic and mechanistic models of bacterial dynamics and development of drug resistance in response to drug therapy are discussed.Expert opinion: Both theories and applications of these approaches provide an overall understanding of how the tools can streamline drug development process and help make crucial decisions. Many opportunities and potentials are presented to incorporate more rigorous integration of PK-PD modeling approaches even at preclinical stage to extrapolate to clinical settings, thus enabling successful trials and optimizing dosing strategies in relevant populations where the drug is mostly used.
C1 [Sy, Sherwin K. B.; Zhuang, Luning; Derendorf, Hartmut] Univ Florida, Coll Pharm, Dept Pharmaceut, Gainesville, FL 32610 USA.
[Sy, Sherwin K. B.] Univ Estadual Maringa, Postgrad Program Biostat, Maringa, Parana, Brazil.
[Zhuang, Luning] US FDA, Div Pharmacometr, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Derendorf, H (reprint author), Univ Florida, Coll Pharm, Dept Pharmaceut, POB 100494, Gainesville, FL 32610 USA.
EM hartmut@ufl.edu
OI Sy, Sherwin/0000-0001-6405-9130
NR 138
TC 4
Z9 4
U1 4
U2 17
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1742-5255
EI 1744-7607
J9 EXPERT OPIN DRUG MET
JI Expert Opin. Drug Metab. Toxicol.
PD JAN 2
PY 2016
VL 12
IS 1
BP 93
EP 114
DI 10.1517/17425255.2016.1123250
PG 22
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA DA5HK
UT WOS:000367833700002
PM 26652832
ER
PT J
AU Gray, PJ
Conklin, SD
Todorov, TI
Kasko, SM
AF Gray, Patrick J.
Conklin, Sean D.
Todorov, Todor I.
Kasko, Sasha M.
TI Cooking rice in excess water reduces both arsenic and enriched vitamins
in the cooked grain
SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL
EXPOSURE & RISK ASSESSMENT
LA English
DT Article
DE Rice; arsenic; inorganic arsenic; iron; cadmium; washing; cooking;
folate; niacin; thiamin
ID RISK ASSESSMENTS; UNITED-STATES; ICP-MS; ACCUMULATION; SPECIATION
AB This paper reports the effects of rinsing rice and cooking it in variable amounts of water on total arsenic, inorganic arsenic, iron, cadmium, manganese, folate, thiamin and niacin in the cooked grain. We prepared multiple rice varietals both rinsed and unrinsed and with varying amounts of cooking water. Rinsing rice before cooking has a minimal effect on the arsenic (As) content of the cooked grain, but washes enriched iron, folate, thiamin and niacin from polished and parboiled rice. Cooking rice in excess water efficiently reduces the amount of As in the cooked grain. Excess water cooking reduces average inorganic As by 40% from long grain polished, 60% from parboiled and 50% from brown rice. Iron, folate, niacin and thiamin are reduced by 50-70% for enriched polished and parboiled rice, but significantly less so for brown rice, which is not enriched.
C1 [Gray, Patrick J.; Conklin, Sean D.; Todorov, Todor I.; Kasko, Sasha M.] US FDA, Div Bioanalyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20742 USA.
RP Gray, PJ (reprint author), US FDA, Div Bioanalyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20742 USA.
EM Patrick.Gray@fda.hhs.gov
OI Gray, Patrick/0000-0002-8248-2749
NR 36
TC 1
Z9 1
U1 10
U2 29
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1944-0049
EI 1944-0057
J9 FOOD ADDIT CONTAM A
JI Food Addit. Contam. Part A-Chem.
PD JAN 2
PY 2016
VL 33
IS 1
BP 78
EP 85
DI 10.1080/19440049.2015.1103906
PG 8
WC Chemistry, Applied; Food Science & Technology; Toxicology
SC Chemistry; Food Science & Technology; Toxicology
GA CY6NM
UT WOS:000366526000009
PM 26515534
ER
PT J
AU Naeger, LK
Harrington, P
Komatsu, T
Deming, D
AF Naeger, Lisa K.
Harrington, Patrick
Komatsu, Takashi
Deming, Damon
TI Effect of dolutegravir functional monotherapy on HIV-1 virological
response in integrase strand transfer inhibitor resistant patients
SO ANTIVIRAL THERAPY
LA English
DT Article
AB Background: VIKING-4 assessed the safety and efficacy of dolutegravir in heavily antiretroviral treatment-experienced patients who had documented integrase strand transfer inhibitor (INSTI) resistance-associated substitutions in their HIV. VIKING-4 had a placebo-controlled 7-day dolutegravir functional monotherapy phase followed by dolutegravir plus an optimized background regimen for 48 weeks.
Methods: Independent resistance analyses evaluated week 48 virological responses in the VIKING-4 trial based on the presence of baseline INSTI resistance-associated substitutions and baseline dolutegravir phenotypic susceptibility. Response rates at week 48 based on baseline dolutegravir resistance subgroups were compared for the 7-day dolutegravir functional monotherapy arm and placebo-control arm. Additionally, genotypic and phenotypic resistance at day 8 and time of failure was analysed for the virological failures from both arms.
Results: Week 48 response rates for VIKING-4 were 23% (3/13) in the 7-day dolutegravir functional monotherapy arm compared with 60% (9/15) in the 7-day placebo arm. Response rates were consistently lower in the dolutegravir functional monotherapy arm across baseline INSTI genotypic and phenotypic subgroups. There was a higher proportion of virological failures in the 7-day dolutegravir functional monotherapy arm (n= 6/13; 46%) compared with the 7-day placebo arm (n= 3/15; 20%). Additionally, five virological failures in the dolutegravir arm had virus expressing emergent INSTI resistance-associated substitutions compared with two in the placebo arm.
Conclusions: Analysis of response rates and resistance emergence in VIKING-4 suggests careful consideration should be given to the duration of functional monotherapy in future studies of highly treatment-experienced patients to reduce the risk of resistance and virological failure.
C1 [Naeger, Lisa K.; Harrington, Patrick; Komatsu, Takashi; Deming, Damon] US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Naeger, LK (reprint author), US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
EM lisa.naeger@fda.hhs.gov
NR 4
TC 1
Z9 1
U1 1
U2 1
PU INT MEDICAL PRESS LTD
PI LONDON
PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND
SN 1359-6535
J9 ANTIVIR THER
JI Antivir. Ther.
PY 2016
VL 21
IS 6
BP 481
EP 488
DI 10.3851/IMP3033
PG 8
WC Infectious Diseases; Pharmacology & Pharmacy; Virology
SC Infectious Diseases; Pharmacology & Pharmacy; Virology
GA EN6BN
UT WOS:000396089600002
PM 26866979
ER
PT S
AU Sakellaropoulos, T
Hur, J
Melas, IN
Guo, EY
Alexopoulos, L
Bohlooly, M
Bai, JPF
AF Sakellaropoulos, Theodore
Hur, Junguk
Melas, Ioannis N.
Guo, Ellen Y.
Alexopoulos, Leonidas
Bohlooly, Mohammad
Bai, Jane P. F.
BE Donev, R
TI Computational Approaches to Accelerating Novel Medicine and Better
Patient Care from Bedside to Benchtop
SO ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY, VOL 102:
PERSONALIZED MEDICINE
SE Advances in Protein Chemistry and Structural Biology
LA English
DT Review; Book Chapter
ID PROTEIN-PROTEIN INTERACTIONS; PRIMARY BREAST-CANCER; CELL LUNG-CANCER;
COLORECTAL-CANCER; MISSENSE MUTATIONS; BIOMEDICAL TEXT; TYROSINE KINASE;
GENE-EXPRESSION; EOSINOPHILIC LEUKEMIA; ENRICHMENT ANALYSIS
AB Some successes have been achieved in the war on cancer over the past 30 years with recent efforts on protein kinase inhibitors. Nonetheless, we are still facing challenges due to cancer evolution. Cancers are complex and heterogeneous due to primary and secondary mutations, with phenotypic and molecular heterogeneity manifested among patients of a cancer, and within an individual patient throughout the disease course. Our understanding of cancer genomes has been facilitated by advances in omics and in bioinformatics technologies; major areas in cancer research are advancing in parallel on many fronts. Computational methods have been developed to decipher the molecular complexity of cancer and to identify driver mutations in cancers. Utilizing the identified driver mutations to develop effective therapy would require biological linkages from cellular context to clinical implication; for this purpose, computational mining of biomedical literature facilitates utilization of a huge volume of biomedical research data and knowledge. In addition, frontier technologies, such as genome editing technologies, are facilitating investigation of cancer mutations, and opening the door for developing novel treatments to treat diseases. We will review and highlight the challenges of treating cancers, which behave like moving targets due to mutation and evolution, and the current state-of-the-art research in the areas mentioned above.
C1 [Sakellaropoulos, Theodore; Bai, Jane P. F.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Hur, Junguk] Univ North Dakota, Sch Med & Hlth Sci, Dept Biomed Sci, Grand Forks, ND USA.
[Melas, Ioannis N.] Astrazeneca, Discovery Sci, Grp Quantitat Biol, Molndal, Sweden.
[Guo, Ellen Y.] Univ Illinois, Mol & Cellular Biol Liberal Arts & Sci, Urbana, IL USA.
[Alexopoulos, Leonidas] Natl Tech Univ Athens, Sch Mech Engn, Athens, Greece.
[Alexopoulos, Leonidas] ProtAtonce Ltd, Athens, Greece.
[Bohlooly, Mohammad] Astrazeneca, Discovery Sci Reagents & Assay Dev, Transgen Grp, Molndal, Sweden.
RP Bai, JPF (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
EM jane.bai@fda.hhs.gov
OI Hur, Junguk/0000-0002-0736-2149
NR 146
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1876-1623
BN 978-0-12-804795-8
J9 ADV PROTEIN CHEM STR
JI Adv. Protein Chem. Struct. Biol.
PY 2016
VL 102
BP 147
EP 179
DI 10.1016/bs.apcsb.2015.09.005
PG 33
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BG9NQ
UT WOS:000393455000007
PM 26827605
ER
PT J
AU Huang, Y
Havert, M
Gavin, D
Serabian, M
Ong, LL
McIntyre, MC
Ferry, N
Kume, A
Petrin, D
Fu, YH
Marti, A
Oliveira, F
Pavittranon, S
Shin, W
AF Huang, Ying
Havert, Mike
Gavin, Denise
Serabian, Mercedes
Ong, Lee Lee
McIntyre, Maritza C.
Ferry, Nicolas
Kume, Akihiro
Petrin, Dino
Fu, Ying-Hsien
Marti, Andreas
Oliveira, Fabricio
Pavittranon, Sumol
Shin, Won
TI Biodistribution studies: understanding international expectations
SO MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
LA English
DT Editorial Material
C1 [Huang, Ying; Havert, Mike; Gavin, Denise; Serabian, Mercedes] US FDA, Silver Spring, MD 20993 USA.
[Ong, Lee Lee] Singapore Hlth Sci Author, Singapore, Singapore.
[McIntyre, Maritza C.] Bamboo Therapeut Inc Chapel Hill, Chapel Hill, NC USA.
[Ferry, Nicolas] European Med Agcy, London, England.
[Kume, Akihiro] Pharmaceut & Med Device Agcy Japan, Tokyo, Japan.
[Petrin, Dino] Hlth Canada, Ottawa, ON, Canada.
[Fu, Ying-Hsien] Taiwan Food & Drug Adm Chinese Taipei, Taipei, Taiwan.
[Marti, Andreas] Swissmed Berne, Bern, Switzerland.
[Oliveira, Fabricio] Natl Hlth Surveillance Agcy Brazil, Setor Ind, Brasilia, DF, Brazil.
[Pavittranon, Sumol] Thailand Ctr Excellence Life Sci, Phayathai Bangkok, Thailand.
[Shin, Won] South Korea Minist Food & Drug Safety, Chungcheongbuk Do, South Korea.
RP Huang, Y; Gavin, D (reprint author), US FDA, Silver Spring, MD 20993 USA.
EM ying.huang@fda.hhs.gov; denise.gavin@fda.hhs.gov
NR 7
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2329-0501
J9 MOL THER-METH CLIN D
JI Mol.Ther.-Methods Clin. Dev.
PY 2016
VL 3
AR UNSP 16022
DI 10.1038/mtm.2016.22
PG 2
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EJ8DM
UT WOS:000393455200033
ER
PT S
AU Akogwu, I
Wang, N
Zhang, CY
Hong, HX
Choi, H
Gong, P
AF Akogwu, Isaac
Wang, Nan
Zhang, Chaoyang
Hong, Huixiao
Choi, Hwanseok
Gong, Ping
BE Tian, T
Jiang, Q
Liu, Y
Burrage, K
Song, J
Wang, Y
Hu, X
Morishita, S
Zhu, Q
Wang, G
TI Factorial Analysis of Error Correction Performance Using Simulated
Next-Generation Sequencing Data
SO 2016 IEEE INTERNATIONAL CONFERENCE ON BIOINFORMATICS AND BIOMEDICINE
(BIBM)
SE IEEE International Conference on Bioinformatics and Biomedicine-BIBM
LA English
DT Proceedings Paper
CT IEEE International Conference on Bioinformatics and Biomedicine (IEEE
BIBM)
CY DEC 15-18, 2016
CL Shenzhen, PEOPLES R CHINA
SP IEEE, IEEE Comp Soc, Natl Sci Fdn, Harbin Inst Technol
DE next-generation sequencing; performance metrics; error correction;
multi-way ANOVA; k-mer spectrum; genome size; read length; coverage
depth; simulation study; precision; F-score
ID SINGLE-NUCLEOTIDE VARIANTS; READS; BIAS
AB Error correction is a critical initial step in next-generation sequencing (NGS) data analysis. Although more than 60 tools have been developed, there is no systematic evidence-based comparison with regard to their strength and weakness, especially in terms of correction accuracy. Here we report a full factorial simulation study to examine how NGS dataset characteristics (genome size, coverage depth and read length in particular) affect error correction performance (precision and F-score), as well as to compare performance sensitivity/resistance of six k-mer spectrum-based methods to variations in dataset characteristics. Multi-way ANOVA tests indicate that choice of correction method and dataset characteristics had significant effects on performance metrics. Overall, BFC, Bless, Bloocoo and Musket performed better than Lighter and Trowel on 27 synthetic datasets. For each chosen method, read length and coverage depth showed more pronounced impact on performance than genome size. This study shed insights to the performance behavior of error correction methods in response to the common variables one would encounter in real-world NGS datasets. It also warrants further studies of wet lab-generated experimental NGS data to validate findings obtained from this simulation study.
C1 [Akogwu, Isaac; Wang, Nan; Zhang, Chaoyang] Univ Southern Mississippi, Sch Comp, Hattiesburg, MS 39406 USA.
[Hong, Huixiao] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR USA.
[Choi, Hwanseok] Univ Southern Mississippi, Dept Publ Hlth, Hattiesburg, MS 39406 USA.
[Gong, Ping] US Army Engn Res & Dev Ctr, Environm Lab, Vicksburg, MS USA.
RP Zhang, CY (reprint author), Univ Southern Mississippi, Sch Comp, Hattiesburg, MS 39406 USA.
EM Chaoyang.zhang@usm.edu; Ping.Gong@usace.army.mil
FU U.S. Army Environmental Quality/Installation (EQI) Basic Research
Program; National Science Foundation [EPS 0903787]
FX This work was supported by an intramural grant from the U.S. Army
Environmental Quality/Installation (EQI) Basic Research Program to PG
and a sub-award of National Science Foundation award EPS 0903787 to CZ
and NW. Permission was granted by the Chief of Engineer to publish this
paper.
NR 24
TC 0
Z9 0
U1 0
U2 0
PU IEEE COMPUTER SOC
PI LOS ALAMITOS
PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA
SN 2156-1125
BN 978-1-5090-1610-5
J9 IEEE INT C BIOINFORM
PY 2016
BP 1164
EP 1169
PG 6
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA BG9GY
UT WOS:000393191700200
ER
PT S
AU Islam, MA
Lim, H
Paoletti, N
Abbas, H
Jiang, ZH
Cyranka, J
Cleaveland, R
Gao, SC
Clarke, E
Grosu, R
Mangharam, R
Cherry, E
Fenton, F
Gray, RA
Glimm, J
Lin, S
Wang, QS
Smolka, SA
AF Islam, Md. Ariful
Lim, Hyunkyung
Paoletti, Nicola
Abbas, Houssam
Jiang, Zhihao
Cyranka, Jacek
Cleaveland, Rance
Gao, Sicun
Clarke, Edmund
Grosu, Radu
Mangharam, Rahul
Cherry, Elizabeth
Fenton, Flavio
Gray, Richard A.
Glimm, James
Lin, Shan
Wang, Qinsi
Smolka, Scott A.
BE Tian, T
Jiang, Q
Liu, Y
Burrage, K
Song, J
Wang, Y
Hu, X
Morishita, S
Zhu, Q
Wang, G
TI CyberCardia Project: Modeling, Verification and Validation of
Implantable Cardiac Devices
SO 2016 IEEE INTERNATIONAL CONFERENCE ON BIOINFORMATICS AND BIOMEDICINE
(BIBM)
SE IEEE International Conference on Bioinformatics and Biomedicine-BIBM
LA English
DT Proceedings Paper
CT IEEE International Conference on Bioinformatics and Biomedicine (IEEE
BIBM)
CY DEC 15-18, 2016
CL Shenzhen, PEOPLES R CHINA
SP IEEE, IEEE Comp Soc, Natl Sci Fdn, Harbin Inst Technol
DE Cardiac electrophysiology; Implantable cardiac Devices; Formal Methods;
Verification and Validation; Closed-loop control
ID PERIOD-DOUBLING BIFURCATIONS; ACTION-POTENTIAL PROPAGATION;
COMPUTATIONAL MODELS; VIRTUAL ELECTRODES; SPIRAL BREAKUP; FIBRILLATION;
DEFIBRILLATION; DYNAMICS; TISSUE; STIMULATION
AB In this paper, we survey recent progress in CyberCardia project, a CPS Frontier project funded by the National Science Foundation. The CyberCardia project will lead to significant advances in the state of the art for system verification and cardiac therapies based on the use of formal methods and closed-loop control and verification. The animating vision for the work is to enable the development of a true in silico design methodology for medical devices that can be used to speed the development of new devices and to provide greater assurance that their behavior matches designer intentions, and to pass regulatory muster more quickly so that they can be used on patients needing their care.
The acceleration in medical-device innovation achievable as a result of the CyberCardia research will also have long-term and sustained societal benefits, as better diagnostic and therapeutic technologies enter into the practice of medicine more quickly.
C1 [Islam, Md. Ariful; Clarke, Edmund; Wang, Qinsi] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA.
[Cyranka, Jacek] Rutgers State Univ, New Brunswick, NJ USA.
[Lim, Hyunkyung; Paoletti, Nicola; Glimm, James; Lin, Shan; Smolka, Scott A.] SUNY Stony Brook, Stony Brook, NY 11794 USA.
[Cleaveland, Rance] Univ Maryland, College Pk, MD 20742 USA.
[Gao, Sicun] MIT, Cambridge, MA 02139 USA.
[Grosu, Radu] Vienna Univ Technol, Vienna, Austria.
[Abbas, Houssam; Jiang, Zhihao; Mangharam, Rahul] Univ Penn, Philadelphia, PA 19104 USA.
[Cherry, Elizabeth] Rochester Inst Technol, Rochester, MN USA.
[Fenton, Flavio] Georgia Inst Technol, Atlanta, GA 30332 USA.
[Gray, Richard A.] US FDA, Rockville, MD 20857 USA.
RP Islam, MA (reprint author), Carnegie Mellon Univ, Pittsburgh, PA 15213 USA.
FU NSF [IIS-1447549, CPS-1446832, CPS-1446725, CAR 1054247]; AFOSR
[FA9550-14-1-0261, YIP FA9550-12-1-0336, CCF-0926190]; ONR
[N00014-13-1-0090]; NASA [NNX12AN15H]
FX Research supported in part by the following grants: NSF IIS-1447549, NSF
CPS-1446832, NSF CPS-1446725, NSF CAR 1054247, AFOSR FA9550-14-1-0261,
AFOSR YIP FA9550-12-1-0336, CCF-0926190, ONR N00014-13-1-0090, and NASA
NNX12AN15H.
NR 51
TC 0
Z9 0
U1 0
U2 0
PU IEEE COMPUTER SOC
PI LOS ALAMITOS
PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA
SN 2156-1125
BN 978-1-5090-1610-5
J9 IEEE INT C BIOINFORM
PY 2016
BP 1445
EP 1452
PG 8
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA BG9GY
UT WOS:000393191700252
ER
PT J
AU Brannen, KC
Chapin, RE
Jacobs, AC
Green, ML
AF Brannen, Kimberly C.
Chapin, Robert E.
Jacobs, Abigail C.
Green, Maia L.
TI Alternative Models of Developmental and Reproductive Toxicity in
Pharmaceutical Risk Assessment and the 3Rs
SO ILAR JOURNAL
LA English
DT Review
DE alternative; developmental toxicity; embryonic stem cells; reproductive
toxicity; whole embryo culture; zebrafish; testis; ovary
ID WHOLE-EMBRYO CULTURE; ZEBRAFISH DANIO-RERIO; METABOLIC-ACTIVATION
SYSTEM; VITRO EMBRYOTOXICITY TESTS; STEM-CELL TEST; IN-VITRO; TOXICOLOGY
ASSAY; PHASE-I; TESTICULAR TOXICITY; BRACHYDANIO-RERIO
AB In the pharmaceutical industry, preclinical developmental and reproductive toxicity studies are conducted in laboratory animals in order to predict and prevent adverse effects of drugs on human reproductive health and development. However, these studies require a relatively large number of animals and are usually conducted late in the drug development process. Early, simple, and inexpensive screening assays could facilitate smarter decisions, reductions in animal use, and development of safe drugs. The current state and future needs for alternative models of developmental and reproductive toxicity are reviewed here. The most popular predictive developmental toxicity assays are embryonic stem cells, rodent whole embryo culture, and zebrafish, each of which involves fairly well-developed techniques with demonstrated utility in drug discovery and development. In vitro or ex vivo methods for male and female reproductive toxicity are less established, but there are promising assays available or being developed that may be useful in drug development, especially for elucidating mechanisms or screening backup compounds. While a number of challenges remain, much progress has been made in alternative developmental and reproductive toxicity models to date, and there is a strong collective enthusiasm in the industry to continue moving them forward. Therefore, it appears that these approaches may be widely used in the near future.
C1 [Brannen, Kimberly C.; Green, Maia L.] Merck & Co Inc, Safety Assessment & Lab Anim Resources, West Point, PA USA.
[Chapin, Robert E.] Pfizer Inc, Dev & Reprod Toxicol Ctr, Groton, CT 06340 USA.
[Jacobs, Abigail C.] US FDA, Pharmacol Toxicol, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Brannen, KC (reprint author), Merck & Co Inc, MRL, West Point, PA 19486 USA.
EM kimberly.brannen@merck.com
NR 101
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1084-2020
EI 1930-6180
J9 ILAR J
JI ILAR J.
PY 2016
VL 57
IS 2
BP 144
EP 156
DI 10.1093/ilar/ilw026
PG 13
WC Veterinary Sciences
SC Veterinary Sciences
GA EJ3HI
UT WOS:000393102800005
PM 28053068
ER
PT J
AU Sistare, FD
Mattes, WB
LeCluyse, EL
AF Sistare, Frank D.
Mattes, William B.
LeCluyse, Edward L.
TI The Promise of New Technologies to Reduce, Refine, or Replace Animal Use
while Reducing Risks of Drug Induced Liver Injury in Pharmaceutical
Development
SO ILAR JOURNAL
LA English
DT Review
DE drug induced liver injury; hepatocyte; in vitro; predictive toxicology;
liver biomarkers; high-content screening; computational model
ID SALT EXPORT PUMP; PLURIPOTENT STEM-CELLS; ACETAMINOPHEN-INDUCED
HEPATOTOXICITY; PRIMARY HUMAN HEPATOCYTES; PRIMARY RAT HEPATOCYTES;
IN-VITRO TOXICITY; MITOCHONDRIAL TOXICITY; MICROPATTERNED COCULTURES;
MATHEMATICAL-MODEL; GENE-EXPRESSION
AB Drug induced liver injury (DILI) has contributed more to marketed pharmaceutical withdrawals and clinical development failures than any other human organ toxicity. DILI seen in animal studies also frequently leads to the discontinuation of promising drug candidates very early in the pipeline. This manuscript reviews and critically assesses the current regulatory expectations; the current drug development approaches, strategies, and gaps; and the numerous exciting opportunities becoming available to address these gaps through technological advances. Emerging integrated pharmaceutical development strategies, while far from uniform, have generally evolved to currently inform early DILI risk potential using supplemental assays for reactive metabolite formation, mitochondrial toxicity, inhibition of bile salt transport, and cellular imaging endpoints including cytotoxicity. Despite these approaches and robust animal testing, significant gaps in addressing human DILI remain. Increasingly sophisticated in vitro humanized test systems, new animal models, emerging computational models, and novel translational biomarkers are being introduced to improve our ability to more accurately predict DILI. Expectations are high for a future state with more predictive tools and problem solving strategies that will improve pharmaceutical discovery and development in relation to understanding human DILI risk potential and make it less dependent on animal studies for successfully developing safer drug candidates.
C1 [Sistare, Frank D.] Merck & Co Inc, Safety Assessment & Lab Anim Resources, West Point, PA USA.
[Mattes, William B.] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR USA.
[LeCluyse, Edward L.] LifeNet Hlth, Res Triangle Pk, NC USA.
RP Sistare, FD (reprint author), Merck & Co Inc, WP 45-205,770 Sumneytown Pike, West Point, PA 19486 USA.
EM frank.sistare@merck.com
NR 198
TC 0
Z9 0
U1 3
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1084-2020
EI 1930-6180
J9 ILAR J
JI ILAR J.
PY 2016
VL 57
IS 2
BP 186
EP 211
DI 10.1093/ilar/ilw025
PG 26
WC Veterinary Sciences
SC Veterinary Sciences
GA EJ3HI
UT WOS:000393102800009
PM 28053072
ER
PT J
AU Centeno, JA
Forcada, EG
Bua, PP
AF Antonio Centeno, Jose
Gimenez Forcada, Elena
Pena Bua, Pilar
TI Medical Geology: An Emerging Discipline
SO REVISTA DE SALUD AMBIENTAL
LA Spanish
DT Editorial Material
C1 [Antonio Centeno, Jose] IMGA, Asociac Int Geol Med, Int Med Geol Assoc, Lausanne, Switzerland.
[Antonio Centeno, Jose] US FDA, Comis Geociencias Gest Medioambiental UGS, Conferencias Int MedGeo Delegado USA, Rockville, MD 20857 USA.
[Gimenez Forcada, Elena] IGME, Asociac Int Geol Med, Int Med Geol Assoc, IMGA, Madrid, Spain.
[Pena Bua, Pilar] Univ Salamanca, Capitulo Espanol Asociac Int Geol Med, Int Med Geol Assoc, IMGA,UPSA, E-37008 Salamanca, Spain.
RP Centeno, JA (reprint author), IMGA, Asociac Int Geol Med, Int Med Geol Assoc, Lausanne, Switzerland.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SOC ESPANOLA SANIDAD AMBIENTAL
PI MADRID
PA C LONDRES 17, MADRID, 28028, SPAIN
SN 1577-9572
EI 1697-2791
J9 REV SALUD AMBIENT
JI Rev. Salud Ambient.
PY 2016
VL 16
IS 2
BP 164
EP 168
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EI2CK
UT WOS:000392293900009
ER
PT J
AU Holland, TL
Mikita, S
Bloom, D
Roberts, J
McCall, J
Collyar, D
Santiago, J
Tiernan, R
Toerner, J
AF Holland, Thomas L.
Mikita, Stephen
Bloom, Diane
Roberts, Jamie
McCall, Jonathan
Collyar, Deborah
Santiago, Jonas
Tiernan, Rosemary
Toerner, Joseph
TI Patient and physician attitudes regarding risk and benefit in
streamlined development programmes for antibacterial drugs: a
qualitative analysis
SO BMJ OPEN
LA English
DT Article
ID CHALLENGES; FUTURE
AB Objectives: To explore patient, caregiver and physician perceptions and attitudes regarding the balance of benefit and risk in using antibacterial drugs developed through streamlined development processes.
Design: Semistructured focus groups and in-depth interviews were conducted to elicit perceptions and attitudes about the use of antibacterial drugs to treat multidrug-resistant infections.
Participants were given background information about antibiotic resistance, streamlined drug development programmes and FDA drug approval processes. Audio recordings of focus groups/interviews were reviewed and quotes excerpted and categorised to identify key themes. Participants: Two primary stakeholder groups were engaged: one comprising caregivers, healthy persons and patients who had recovered from or were at risk of resistant infection (N=67; 11 focus groups); and one comprising physicians who treat resistant infections (N=23).
Results: Responses from focus groups/interviews indicated widespread awareness among patients/caregivers and physicians of the seriousness of the problem of antibacterial resistance. Both groups were willing to accept a degree of uncertainty regarding the balance of risk and benefit in a new therapy where a serious unmet need exists, but also expressed a desire for rigorous monitoring and rapid, transparent reporting of safety/effectiveness data. Both groups wanted to ensure that >1 physician had input on whether to treat patients with antibiotics developed through a streamlined process. Some patients/ caregivers unfamiliar with exigencies of critical care suggested a relatively large multidisciplinary team, while physicians believed individual expert consultations would be preferable. Both groups agreed that careful oversight and stewardship of antibacterial drugs are needed to ensure patient safety, preserve efficacy and prevent abuse.
Conclusions: Groups comprising patients/caregivers and physicians were aware of serious issues posed by resistant infections and the lack of effective antibacterial drug therapies and shared a consensus that streamlined development programmes represent a necessary response to the resistance crisis, but one that requires enhanced safeguards and risk communication.
C1 [Holland, Thomas L.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA.
[Holland, Thomas L.; Roberts, Jamie; McCall, Jonathan] Duke Clin Res Inst, Durham, NC 27705 USA.
[Mikita, Stephen; Collyar, Deborah] Patient Advocates Res, Danville, CA USA.
[Bloom, Diane] InFocus Res, Chapel Hill, NC USA.
[Santiago, Jonas; Tiernan, Rosemary; Toerner, Joseph] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Holland, TL (reprint author), Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA.; Holland, TL (reprint author), Duke Clin Res Inst, Durham, NC 27705 USA.
EM thomas.holland@duke.edu
FU US Food and Drug Administration [R18FD005292, U19FD003800]; Clinical
Trials Transformation Initiative's member organisations
FX This work was made possible in part by the US Food and Drug
Administration through grant R18FD005292 and cooperative agreement
U19FD003800. Partial funding was also provided by pooled membership fees
from the Clinical Trials Transformation Initiative's member
organisations.
NR 20
TC 0
Z9 0
U1 1
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 2044-6055
J9 BMJ OPEN
JI BMJ Open
PY 2016
VL 6
IS 11
AR e013561
DI 10.1136/bmjopen-2016-013561
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA EG8JQ
UT WOS:000391303400081
PM 28186948
ER
PT J
AU Mahmood, I
AF Mahmood, Iftekhar
TI Prediction of Plasma Concentration-time Profiles of Drugs in Humans from
Animals Following Oral Administration: An Allometric Approach
SO CURRENT DRUG METABOLISM
LA English
DT Article
DE Absorption; allometry; clearance; concentration-time; oral drugs;
pharmacokinetics
ID HUMAN PHARMACOKINETICS; DOSE PHARMACOKINETICS; HEALTHY-VOLUNTEERS;
PRECLINICAL DATA; SCALE-UP; METABOLISM; CLEARANCE; VENLAFAXINE;
EXCRETION; LEVOVIRIN
AB Background: Allometric scaling is regularly used for the prediction of human pharmacokinetic (PK) parameters from animal PK studies. The predicted human PK parameters can also be used for the prediction of plasma concentration-time profiles in humans.
Objectives: The main objective of this work is to predict human concentration-time profiles of drugs (one-compartment model) following oral administration using animal oral pharmacokinetic parameters.
Methods: Six drugs from the literature were chosen that were described by one-compartment model in both humans and animals following oral administration. Pharmacokinetic parameters such as oral clearance, oral volume of distribution of the central compartment, time to reach maximum plasma concentration, absorption rate constant, and half-life in humans were predicted from animals using allometric scaling. These predicted human pharmacokinetic parameters were then used to predict human plasma concentrations-time profiles of drugs.
Results: The results of this study indicate that the proposed method can be used to predict human plasma concentrations-time profiles of drugs with reasonable accuracy (<= 50% prediction error).
Conclusions: Given the complexity in the pharmacokinetics of oral drugs there remains some uncertainty in this entire exercise. One can minimize the prediction error by experience in allometric scaling, scientific judgment, and unconventional or innovative thinking.
C1 [Mahmood, Iftekhar] US FDA, Div Hematol Clin Review, OBRR, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
RP Mahmood, I (reprint author), US FDA, Div Hematol Clin Review, OBRR, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
EM har.mahmood@fda.hhs.gov
NR 36
TC 0
Z9 0
U1 1
U2 1
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1389-2002
EI 1875-5453
J9 CURR DRUG METAB
JI Curr. Drug Metab.
PY 2016
VL 17
IS 10
BP 1006
EP 1013
DI 10.2174/13892002186661611211202
PG 8
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA EH9HV
UT WOS:000392083300007
PM 27903219
ER
PT J
AU Holland, T
Mikita, S
Corneli, A
Roberts, J
McCall, J
Collyar, D
Santiago, J
Tiernan, R
AF Holland, T.
Mikita, S.
Corneli, A.
Roberts, J.
McCall, J.
Collyar, D.
Santiago, J.
Tiernan, R.
TI Streamlining Antibacterial Drug Development Programs To Address Unmet
Medical Need: Patient And Provider Attitudes On A Modified Benefit-Risk
Calculus
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 13-18, 2016
CL San Francisco, CA
SP Amer Thorac Soc
C1 [Holland, T.] Duke Univ, Sch Med, Durham, NC USA.
[Mikita, S.; Collyar, D.] Clin Trials Transformat Initiat, Durham, NC USA.
[Corneli, A.; McCall, J.] Duke Clin Res Inst, Durham, NC USA.
[Roberts, J.] Duke Univ, Durham, NC USA.
[Santiago, J.; Tiernan, R.] US FDA, Silver Spring, MD USA.
EM jamie.roberts@duke.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PY 2016
VL 193
MA A2112
PG 3
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA EG0VE
UT WOS:000390749601252
ER
PT J
AU Pilon, AL
Winn, ME
Clayton, RS
Hariprakasha, H
AF Pilon, A. L.
Winn, M. E.
Clayton, R. S.
Hariprakasha, H.
TI Modification Of Cc10 Protein By Reactive Oxygen Species: A Novel
Anti-Inflammatory Mechanism
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT International Conference of the American-Thoracic-Society (ATS)
CY MAY 13-18, 2016
CL San Francisco, CA
SP Amer Thorac Soc
C1 [Pilon, A. L.; Winn, M. E.; Clayton, R. S.] Therabron Therapeut Inc, Rockville, MD USA.
[Hariprakasha, H.] US FDA, Silver Spring, MD USA.
EM aprile.pilon@therabron.com
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PY 2016
VL 193
MA A5907
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA EG0VE
UT WOS:000390749605568
ER
PT J
AU Irony, T
Ho, M
Christopher, S
Levitan, B
AF Irony, Telba
Ho, Martin
Christopher, Stephanie
Levitan, Bennett
TI Incorporating Patient Preferences into Medical Device Benefit-Risk
Assessments
SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH
LA English
DT Article
DE Benefit-risk tradeoff; Food and Drug Administration (FDA); Minimum
clinically meaningful benefit (MCMB); Patient-centered regulatory
decision-making; Patient-preference elicitation; Preference-sensitive
decision
AB Patients play a unique role in medical device evaluation because they live with their conditions and consequences of the treatments they choose. They may weigh the benefits, risks, and other attributes of treatments differently than physicians and regulators. They may even be heterogenous among themselves when trading-off benefits and risks. Therefore, industry, regulators, and patient groups have a growing interest in exploring how to assess and incorporate patient preferences when conducting benefit-risk assessments of medical devices. This article discusses remarkable developments in this area: a proof-of-concept study on preferences of obese patients conducted by the Center for Devices and Radiological Health at the FDA (CDRH), the guidance documents on factors for benefit-risk determinations and on patient preference information issued recently by CDRH, and the Patient-Centered Benefit-Risk project developed by the Medical Device Innovation Consortium. We will also discuss important concepts related to patient preferences and use the CDRH study results to illustrate them.
C1 [Irony, Telba] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
[Ho, Martin] US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
[Christopher, Stephanie] Med Device Innovat Consortium, Minneapolis, MN USA.
[Levitan, Bennett] Janssen Res & Dev, Dept Epidemiol, Titusville, NJ USA.
RP Irony, T (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM Telba.irony@fda.hhs.gov
FU Broad Agency Agreement from the U.S. Food and Drug Administration [BAA
HHSF223201400011C]
FX Funding for the MDIC Framework and Catalog came from a Broad Agency
Agreement from the U.S. Food and Drug Administration (BAA
HHSF223201400011C "Patient Centeredness: Integrating Patient Preference
into Regulatory Submission.")
NR 12
TC 0
Z9 0
U1 0
U2 0
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 1946-6315
J9 STAT BIOPHARM RES
JI Stat. Biopharm. Res.
PY 2016
VL 8
IS 3
BP 230
EP 236
DI 10.1080/19466315.2015.1135820
PG 7
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA EF5XM
UT WOS:000390403100002
ER
PT J
AU Li, H
Mukhi, V
Lu, N
Xu, YL
Yue, LQ
AF Li, Heng
Mukhi, Vandana
Lu, Nelson
Xu, Yun-Ling
Yue, Lilly Q.
TI A Note on Good Practice of Objective Propensity Score Design for
Premarket Nonrandomized Medical Device Studies with an Example
SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH
LA English
DT Article
DE Balance assessment; Regulatory submission; Stratification
ID BIAS; SUBCLASSIFICATION
AB In this short note, we highlight some key elements of the process of submitting an investigational device exemption of a nonrandomized clinical study that involves the use of propensity score methodology. Focus is given to the assessment of balance for propensity score stratification.
C1 [Li, Heng; Mukhi, Vandana; Lu, Nelson; Xu, Yun-Ling; Yue, Lilly Q.] US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Av,WO 66, Silver Spring, MD 20993 USA.
RP Mukhi, V (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Av,WO 66, Silver Spring, MD 20993 USA.
EM vandana.mukhi@fda.hhs.gov
NR 13
TC 0
Z9 0
U1 0
U2 0
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 1946-6315
J9 STAT BIOPHARM RES
JI Stat. Biopharm. Res.
PY 2016
VL 8
IS 3
BP 282
EP 286
DI 10.1080/19466315.2016.1148071
PG 5
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA EF5XM
UT WOS:000390403100008
ER
PT J
AU Cui, SQ
Zhao, YQ
Tiwari, RC
AF Cui, Shiqi
Zhao, Yueqin
Tiwari, Ram C.
TI Bayesian Approach to Personalized Benefit-Risk Assessment
SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH
LA English
DT Article
DE Benefit-risk measures; Dirichlet process; Generalized linear model;
Gibbs sampling; Metropolis-Hastings algorithm; Model selection
ID GIBBS SAMPLING APPROACH; REGRESSION-MODELS; POSTERIOR SIMULATION;
QUANTITATIVE METHODS; CLINICAL-TRIALS; DISTRIBUTIONS; INFERENCE;
MIXTURES; PRODUCTS; PROPOSAL
AB Benefit-risk assessment is criticalin evaluating the effectiveness of a new drug before and after the approval Some benefit-risk measures depend on the probabilities of benefit-risk categories in which the subject-level benefit and risk outcomes are characterized. The existing benefit-risk methods for analyzing the categorical data depend only on the frequencies of mutually exclusive and collectively exhaustive categories that the subjects fall in, and thus ignore the subject-level differences. We propose a Bayesian method for analyzing he subject-level data with multiple visits. A generalized linear model is used to model the subject-level esporise probability, with respect to a "reference' category, assuming a loft model with subject-level category effects arid multiple visit effects. The random longitudinal visit effects are modeled by a multivariate normal distribution with zero means and first-order autoregressive structured variance-covariance matt' ces. In the proposed Bayesian setup, a Dirichlet process is used as a prior for the subject-level category effect to catch the similarity among the subject responses. We develoP r an efficient Ma kov chain Monte C lo algorithm for implementing the proposed method, and illustrate the estimation of individual benefit risk profiles through simulation. The performance of the proposed model fit is evaluated using two mode election approaches, namely, the deviance information criterion;{DIG) arid the log-pseudo marginal like hood (LPML). We analyze a clinical trial data using the proposed method to assess the subject-level or personalized benefit-risk in each arm, and to evaluate the aggregated benefit-risk difference between the treatments at different visits.
C1 [Cui, Shiqi] Univ Missouri, Dept Stat, Columbia, MO 65211 USA.
[Zhao, Yueqin; Tiwari, Ram C.] US FDA, Off Biostat, Silver Spring, MD 20993 USA.
RP Zhao, YQ (reprint author), US FDA, Div Biometr 7, Off Biostat, OTS,CDER, Silver Spring, MD 20993 USA.
EM Yueqin.Zhao@fda.hhs.gov
NR 39
TC 0
Z9 0
U1 0
U2 0
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 1946-6315
J9 STAT BIOPHARM RES
JI Stat. Biopharm. Res.
PY 2016
VL 8
IS 3
BP 316
EP 324
DI 10.1080/19466315.2016.1193045
PG 9
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA EF5XM
UT WOS:000390403100012
ER
PT J
AU Sun, WJ
Zhou, LJ
Grosser, S
Kim, C
AF Sun, Wanjie
Zhou, Lingjie
Grosser, Stella
Kim, Carol
TI A Meta-Analysis of Missing Data and Non-Compliance Data in Clinical
Endpoint Bioequivalence Studies
SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH
LA English
DT Article
DE Bioequivalence; Meta-analysis; Missing data; Non-compliance data
ID TRIALS
AB Missing data and noncompliance data questions are especially important in evaluating locally acting generic drugs because primary equivalence analyses in clinical endpoint bioequivalence (BE) studies are based on the per-protocol (PP) population (generally, completers and compliers). A meta-analysis using six clinical endpoint BE studies for topical drugs reveals the following: (1) An average of 22% (95% CI: 15-29%) of randomized subjects are excluded from the PP population. (2) Of these excluded subjects, half (10.6%, 95% CI: 8.3-12.8%) dropped out. Most who dropped out (6.9%, 95% CI: 5.0-8.8%) did not specify reasons. (3) Noncompliance categories include out-of-window visits (7.7%, 95% CI: 5.5%-9.8%), dosing noncompliance (<75% or >125% of dose) (5%, 95% CI: 2.7%-7.4%), and restricted medication use (3.2%, 95% CI: 1.8%-4.7%). (4) Drop out and noncompliance are not completely at random: a better treatment effect is associated with less drop out and less noncompliance. (5) Drop out and noncompliance are correlated: noncompliers are more likely to drop out, and vice versa. These results will help regulators better understand the extent and pattern of drop out and noncompliance and shed light on designing appropriate analysis population, endpoints, estimands, and investigating primary and sensitivity methods for equivalence in clinical endpoint BE studies in presence of missing and noncompliance data.
C1 [Sun, Wanjie; Grosser, Stella] US FDA, CDER, Off Biostat, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
[Zhou, Lingjie] George Washington Univ, Dept Stat, Washington, DC 20052 USA.
[Kim, Carol] US FDA, CDER, Off Gener Drugs, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
RP Sun, WJ (reprint author), US FDA, CDER, Off Biostat, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM wanjie.sun@fda.hhs.gov
FU FDA CDLR Regulatory Science and Review (RSR) grant
FX Supported by a FDA CDLR Regulatory Science and Review (RSR) grant.
NR 18
TC 0
Z9 0
U1 0
U2 0
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 1946-6315
J9 STAT BIOPHARM RES
JI Stat. Biopharm. Res.
PY 2016
VL 8
IS 3
BP 334
EP 344
DI 10.1080/19466315.2016.1201000
PG 11
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA EF5XM
UT WOS:000390403100014
ER
PT J
AU Li, MJ
AF Li, Meijuan
TI Statistical Methods for Clinical Validation of Follow-On Companion
Diagnostic Devices via an External Concordance Study
SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH
LA English
DT Article
DE Comparator companion diagnostic device; Devices intended use population;
Device-drug clinical trial; Drug efficacy; Follow-on companion
diagnostic device; Personalized medicine
ID PERSONALIZED MEDICINE; PREDICTIVE VALUES; DESIGNS; TESTS
AB To date there are a number of FDA-approved companion diagnostics for use with specific corresponding therapeutic products. Hence, opportunities exist for device manufacturers to develop follow-on companion diagnostic devices. A follow-on companion diagnostic is intended to be used with the therapeutic product in the indicated patient population, as in the labeling of the comparator companion diagnostic. Thus, information provided by a follow-on companion diagnostic device is essential for the safe and effective use of the corresponding therapeutic product in the comparator companion diagnostic. However, the manufacturer of a follow-on companion diagnostic device may not have a therapeutic partner to conduct a new clinical trial, or there may lack the patient samples from the original clinical trial, where the comparator and therapeutic product were evaluated. As such, an external concordance study is conducted to assess the concordance between the comparator and the follow-on device. Difficulty and challenges arise on how to evaluate the follow-on devices clinical performance based the agreements from an external concordance study. In this article, we will discuss the challenges and issues for the clinical validation of follow-on devices and we aim to provide some statistical methods on how to support clinical validation of follow-on companion diagnostic devices for its proposed indications for use via an external concordance study.
C1 [Li, Meijuan] US FDA, Div Biostat, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
RP Li, MJ (reprint author), US FDA, Div Biostat, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM meijuan.li@fda.hhs.gov
NR 9
TC 0
Z9 0
U1 0
U2 0
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 1946-6315
J9 STAT BIOPHARM RES
JI Stat. Biopharm. Res.
PY 2016
VL 8
IS 3
BP 355
EP 363
DI 10.1080/19466315.2016.1202859
PG 9
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA EF5XM
UT WOS:000390403100016
ER
PT J
AU Wang, YP
Mai, YB
He, WL
AF Wang, Yaping
Mai, Yabing
He, Weili
TI A Quantitative Approach for Benefit-Risk Assessment Using Stochastic
Multi-Criteria Discriminatory Method
SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH
LA English
DT Article
DE Decision making; Partial information; Pharmaceutical
ID ACCEPTABILITY ANALYSIS
AB Benefit-risk (BR) assessment is important to ensure safety and effectiveness of medical projects in clinical development and post marketing surveillance. The evaluation of the balance between benefits and risks of a drug is fundamental to all stakeholders involved in the development, registration, and use of drugs. Many quantitative approaches have been developed that may draw together data from different sources to present them in ways that can aid decision-making. Among these quantitative approaches, multicriteria decision analysis (MCDA) is one of the most useful approaches, since it provides a framework for systematic and replicable analyses of complex decision problems involving value tradeoffs. In most real-life situations, decision makers are not able to get exact preference information (weights). To overcome this limitation of MCDA, a method called stochastic multicriteria acceptability analysis (SMAA) was proposed as a quantitative approach to BR assessment in drug development. The chief advantage of SMAA over most other MCDA methodologies is that it can be used with limited or no preference information and a data-driven approach can be used to obtain the inherent weighting among multicriteria. In this article, we propose the stochastic multicriteria discriminatory method (SMDM) that is based on the SMAA method with a focus on providing straightforward and informative assistance to decision making. We use SMDM to derive probability of better treatment, probability of significantly better treatment and the expected p-values of the evaluation results, on the basis of limited partial weight information or no weight information at all.
C1 [Wang, Yaping] US FDA, Div Biometr 5, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
[Mai, Yabing; He, Weili] Merck Res Labs, Rahway, NJ USA.
RP Wang, YP (reprint author), US FDA, Div Biometr 5, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM Yaping.Wang@fda.hhs.gov
NR 13
TC 0
Z9 0
U1 0
U2 0
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 1946-6315
J9 STAT BIOPHARM RES
JI Stat. Biopharm. Res.
PY 2016
VL 8
IS 4
BP 373
EP 378
DI 10.1080/19466315.2016.1202135
PG 6
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA EF5XN
UT WOS:000390403300003
ER
PT J
AU Ma, HJ
Jiang, Q
Chuang-Stein, C
Evans, SR
He, WL
Quartey, G
Scott, J
Wen, SH
Arani, R
AF Ma, Haijun
Jiang, Qi
Chuang-Stein, Christy
Evans, Scott R.
He, Weili
Quartey, George
Scott, John
Wen, Shihua
Arani, Ramin
TI Considerations on Endpoint Selection, Weighting Determination, and
Uncertainty Evaluation in the Benefit-Risk Assessment of Medical Product
SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH
LA English
DT Article
DE Benefit-risk assessment; Benefit-risk endpoint selection; Uncertainty;
Weighting
ID MULTICRITERIA DECISION-ANALYSIS; CLINICAL-TRIALS; STATISTICAL
CONSIDERATIONS; TASK-FORCE; DISCRETE; METHODOLOGIES; PREFERENCES;
REGRESSION; MEDICINES; FRAMEWORK
AB A structured benefit-risk assessment (BRA) is critical for drug development and lifecycle management. How to select B-R endpoints, determine weighting for these endpoints, and evaluate uncertainties are key aspects of the B-R decision-making process. In this article, we discuss key considerations on endpoint selection, challenges of double counting and correlated endpoints, and methods that can be used to address these challenges. In addition, we discuss the use of qualitative and quantitative weighting in BRA, techniques useful for weight construction, and weights based on empirical preferences. Potential sources for uncertainties in BRA, the approaches to illustrate and to address these uncertainties are described. Finally, we emphasize that benefit-risk assessment is a continuous process and requires cross-functional efforts.
C1 [Ma, Haijun; Jiang, Qi] Amgen Inc, Global Biostat & Epidemiol, Thousand Oaks, CA 91320 USA.
[Chuang-Stein, Christy] Chuang Stein Consulting, Kalamazoo, MI USA.
[Evans, Scott R.] Harvard Sch Publ Hlth, Biostat, Boston, MA USA.
[He, Weili] Merck & Co Inc, Kenilworth, NJ USA.
[Quartey, George] Genentech Inc, 460 Point San Bruno Blvd, San Francisco, CA 94080 USA.
[Scott, John] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
[Wen, Shihua] Novartis Pharmaceut, E Hanover, NJ USA.
[Arani, Ramin] AstraZeneca Pharmaceut LP, Gaithersburg, MD USA.
RP Ma, HJ (reprint author), Amgen Inc, Global Biostat & Epidemiol, Thousand Oaks, CA 91320 USA.
EM hma@amgen.com
NR 42
TC 0
Z9 0
U1 0
U2 0
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 1946-6315
J9 STAT BIOPHARM RES
JI Stat. Biopharm. Res.
PY 2016
VL 8
IS 4
BP 417
EP 425
DI 10.1080/19466315.2016.1234974
PG 9
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA EF5XN
UT WOS:000390403300009
ER
PT J
AU Scott, J
AF Scott, John
TI Comment: Statisticians Staying Involved in Benefit-Risk Assessment
SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH
LA English
DT Editorial Material
C1 [Scott, John] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
RP Scott, J (reprint author), US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 1946-6315
J9 STAT BIOPHARM RES
JI Stat. Biopharm. Res.
PY 2016
VL 8
IS 4
BP 426
EP 427
DI 10.1080/19466315.2016.1213658
PG 2
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA EF5XN
UT WOS:000390403300010
ER
PT J
AU Lee, CT
Boeshore, KL
Wu, C
Becker, KG
Errico, SL
Mash, DC
Freed, WJ
AF Lee, Chun-Ting
Boeshore, Kristen L.
Wu, Chun
Becker, Kevin G.
Errico, Stacie L.
Mash, Deborah C.
Freed, William J.
TI Cocaine promotes primary human astrocyte proliferation via JNK-dependent
up-regulation of cyclin A2
SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE
LA English
DT Article
DE Astrocytes; cocaine; reactive astrogliosis; addiction; JNK; cyclin A
ID CELL-PROLIFERATION; NUCLEUS-ACCUMBENS; STRUCTURAL PLASTICITY; SIGNALING
PATHWAYS; DENDRITIC SPINES; REACTIVE GLIOSIS; GENE ONTOLOGY; IN-VIVO;
EXPRESSION; ACTIVATION
AB Purpose: Astrocytes perform a plethora of important functions in the central nervous system (CNS) and are involved in cocaine-evoked synaptic plasticity. Previously, we showed that while cocaine decreased cyclin A2 expression in primary human neural progenitor cells, it increased cyclin A2 expression in human astrocytes. Since cyclin A2 is an essential regulator of the cell cycle, the aim of the present study is to clarify the effect of cocaine on proliferation of human astrocytes and elucidate the underlying molecular mechanisms.
Methods: Primary human astrocytes were treated with either 1, 10, or 100 mu M cocaine for 48 hr, and cell proliferation was measured using the CyQUANT cell proliferation assay. To elucidate the molecular mechanisms through which cocaine affects the proliferation of astrocytes, we analyzed gene expression profiles in cocaine-treated primary human astrocytes using a human focused cDNA array. Gene ontology/pathway enrichment analysis, STRING protein-protein interaction analysis, RT-qPCR, and western blotting were used to identify signal transduction pathways that are involved in cocaine-induced astrocyte dysfunction.
Results: Cocaine at 10 and 100 mu M significantly increased human astrocyte proliferation. Gene expression profiling revealed the JNK MAP kinase pathway as a driver of cell proliferation affected by cocaine in human astrocytes. Further experiments showed that cocaine-induced JNK activation induced up-regulation of cyclin A2, leading to enhanced proliferation of human astrocytes.
Conclusion: Cocaine-induced abnormal increases in the number of astrocytes may cause disruption in neuron-glia signaling and contribute to synaptic impairment in the CNS. Understanding the mechanisms of cocaine's effects on human astrocytes may help to reveal the involvement of glial cells in addictive behaviors.
C1 [Lee, Chun-Ting; Errico, Stacie L.; Freed, William J.] NIDA, Sect Dev & Plast, Cellular Neurobiol Res Branch, Intramural Res Program,NIH, Baltimore, MD USA.
[Lee, Chun-Ting; Mash, Deborah C.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.
[Boeshore, Kristen L.; Freed, William J.] Lebanon Valley Coll, Dept Biol, Annville, PA USA.
[Wu, Chun; Mash, Deborah C.] Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA.
[Becker, Kevin G.] NIA, Gene Express & Genom Unit, Res Resources Branch, IRP,NIH, Baltimore, MD 21224 USA.
RP Lee, CT (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 52,Rm 1121,10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM Chun-Ting.Lee@fda.hhs.gov
FU Intramural Research Programs of the National Institute on Drug Abuse;
National Institute on Aging
FX This work was supported by the Intramural Research Programs of the
National Institute on Drug Abuse and the National Institute on Aging.
NR 77
TC 0
Z9 0
U1 3
U2 3
PU IOS PRESS
PI AMSTERDAM
PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS
SN 0922-6028
EI 1878-3627
J9 RESTOR NEUROL NEUROS
JI Restor. Neurol. Neurosci.
PY 2016
VL 34
IS 6
BP 965
EP 976
DI 10.3233/RNN-160676
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA EE0DG
UT WOS:000389243100008
PM 27834787
ER
PT S
AU Kalaa, MO
Butron, G
Balid, W
Refai, HH
LaSorte, NJ
AF Al Kalaa, Mohamad Omar
Butron, Gregory
Balid, Walid
Refai, Hazem H.
LaSorte, Nickolas J.
GP IEEE
TI Long Term Spectrum Survey of the 2.4 GHz ISM Band in Multiple Hospital
Environments
SO 2016 IEEE WIRELESS COMMUNICATIONS AND NETWORKING CONFERENCE
SE IEEE Wireless Communications and Networking Conference
LA English
DT Proceedings Paper
CT IEEE Wireless Communications and Networking Conference (WCNC)
CY APR 03-07, 2016
CL Doha, QATAR
SP IEEE, IEEE Commun Soc
AB Wireless technology has become an invaluable facilitator in many aspects of daily life. Healthcare environments in particular have gained noticeable agility and flexibility by integrating wireless functionality into various medical equipment. As of late, chipsets designed to implement communication standards in the Industrial, Scientific and Medical (ISM) band have become inexpensive and widely available, making wireless-enabled medical devices reach increased number of users. However, the sharp increase in the number of operating nodes now occupying the ISM band has resulted in a cluttered spectrum with limited resources in many environments.
In this paper, we report on a long term spectrum survey of the ISM band in both an intensive care unit (ICU) and a post-surgery recovery room (RR). Both spaces were concurrently surveyed for 28 consecutive days capturing spectrum occupancy on every weekday four times. Results indicate that spectrum occupancy patterns are location dependent. Examined sub-channels with significant correlation in activity pattern corresponded mainly to IEEE 802.11 channels 1, 6, and 11. Low daily duty cycle is indicated at a maximum of 5.17% at RR and 3.11% at ICU.
C1 [Al Kalaa, Mohamad Omar; Butron, Gregory; Balid, Walid; Refai, Hazem H.] Univ Oklahoma, Dept Elect & Comp Engn, Norman, OK 73019 USA.
[LaSorte, Nickolas J.] US FDA, Rockville, MD 20857 USA.
RP Kalaa, MO (reprint author), Univ Oklahoma, Dept Elect & Comp Engn, Norman, OK 73019 USA.
EM omarqal@ou.edu; gregorybutron@ou.edu; walid@ou.edu; hazem@ou.edu;
Nickolas.Lasorte@fda.hhs.gov
NR 26
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 1525-3511
BN 978-1-4673-9814-5
J9 IEEE WCNC
PY 2016
PG 6
WC Telecommunications
SC Telecommunications
GA BG4CR
UT WOS:000388603100042
ER
PT J
AU Theunissen, PT
Beken, S
Beyer, BK
Breslin, WJ
Cappon, GD
Chen, CL
Chmielewski, G
De Schaepdrijver, L
Enright, B
Foreman, JE
Harrouk, W
Hew, KW
Hoberman, AM
Hui, JY
Knudsen, TB
Laffan, SB
Makris, SL
Martin, M
McNerney, ME
Siezen, CL
Stanislaus, DJ
Stewart, J
Thompson, KE
Tornesi, B
Van der Laan, JW
Weinbauer, GF
Wood, S
Piersma, AH
AF Theunissen, Peter T.
Beken, Sonja
Beyer, Bruce K.
Breslin, William J.
Cappon, Gregg D.
Chen, Connie L.
Chmielewski, Gary
De Schaepdrijver, Luc
Enright, Brian
Foreman, Jennifer E.
Harrouk, Wafa
Hew, Kok-Wah
Hoberman, Alan M.
Hui, Julia Y.
Knudsen, Thomas B.
Laffan, Susan B.
Makris, Susan L.
Martin, Matt
McNerney, Mary Ellen
Siezen, Christine L.
Stanislaus, Dinesh J.
Stewart, Jane
Thompson, Kary E.
Tornesi, Belen
Van der Laan, Jan Willem
Weinbauer, Gerhard F.
Wood, Sandra
Piersma, Aldert H.
TI Comparison of rat and rabbit embryo-fetal developmental toxicity data
for 379 pharmaceuticals: on the nature and severity of developmental
effects
SO CRITICAL REVIEWS IN TOXICOLOGY
LA English
DT Review
DE Pharmaceutical testing; embryo-fetal developmental toxicity;
cross-species evaluation; non-clinical
ID IN-VITRO; THALIDOMIDE; ABNORMALITIES; ANIMALS
AB Regulatory non-clinical safety testing of human pharmaceuticals typically requires embryo-fetal developmental toxicity (EFDT) testing in two species (one rodent and one non-rodent). The question has been raised whether under some conditions EFDT testing could be limited to one species, or whether the testing in a second species could be decided on a case-by-case basis. As part of a consortium initiative, we built and queried a database of 379 compounds with EFDT studies (in both rat and rabbit animal models) conducted for marketed and non-marketed pharmaceuticals for their potential for adverse developmental and maternal outcomes, including EFDT incidence and the nature and severity of adverse findings. Manifestation of EFDT in either one or both species was demonstrated for 282 compounds (74%). EFDT was detected in only one species (rat or rabbit) in almost a third (31%, 118 compounds), with 58% (68 compounds) of rat studies and 42% (50 compounds) of rabbit studies identifying an EFDT signal. For 24 compounds (6%), fetal malformations were observed in one species (rat or rabbit) in the absence of any EFDT in the second species. In general, growth retardation, fetal variations, and malformations were more prominent in the rat, whereas embryo-fetal death was observed more often in the rabbit. Discordance across species may be attributed to factors such as maternal toxicity, study design differences, pharmacokinetic differences, and pharmacologic relevance of species. The current analysis suggests that in general both species are equally sensitive on the basis of an overall EFDT LOAEL comparison, but selective EFDT toxicity in one species is not uncommon. Also, there appear to be species differences in the prevalence of various EFDT manifestations (i.e. embryo-fetal death, growth retardation, and dysmorphogenesis) between rat and rabbit, suggesting that the use of both species has a higher probability of detecting developmental toxicants than either one alone.
C1 [Theunissen, Peter T.; Van der Laan, Jan Willem; Piersma, Aldert H.] Natl Inst Publ Hlth & Environm RIVM, Ctr Hlth Protect, Bilthoven, Netherlands.
[Theunissen, Peter T.; Siezen, Christine L.; Van der Laan, Jan Willem] Med Evaluat Board, Graadt van Roggenweg 500, NL-3531 AH Utrecht, Netherlands.
[Theunissen, Peter T.] Univ Appl Sci Utrecht HU, Innovat Testing Life Sci & Chem, Utrecht, Netherlands.
[Beken, Sonja] Fed Agcy Med & Hlth Prod, Brussels, Belgium.
[Beyer, Bruce K.] Sanofi US Inc, Bridgewater, NJ USA.
[Breslin, William J.] Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN USA.
[Cappon, Gregg D.] Pfizer Worldwide Res & Dev, Groton, CT USA.
[Chen, Connie L.] ILSI Hlth & Environm Sci Inst, Washington, DC USA.
[Chmielewski, Gary] Covance Labs Inc, Greenfield, IN USA.
[De Schaepdrijver, Luc] Janssen R&D, Preclin Dev & Safety Beerse, Beerse, Belgium.
[Enright, Brian; Tornesi, Belen] AbbVie Inc, N Chicago, IL USA.
[Foreman, Jennifer E.] ExxonMobil Biomed Sci Inc, Annandale, NJ USA.
[Harrouk, Wafa] US FDA, Silver Spring, MD USA.
[Hew, Kok-Wah] Takeda Pharmaceut Co, Deerfield, IL USA.
[Hoberman, Alan M.] Charles River Labs, Preclin Serv, Horsham, PA USA.
[Hui, Julia Y.] Celgene Corp, Summit, NJ USA.
[Knudsen, Thomas B.; Martin, Matt] US EPA, Natl Ctr Computat Toxicol, Res Triangle Pk, NC 27711 USA.
[Laffan, Susan B.; Stanislaus, Dinesh J.] GlaxoSmithKline, Safety Assessment, King Of Prussia, PA USA.
[Makris, Susan L.] US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA.
[McNerney, Mary Ellen; Thompson, Kary E.] Bristol Myers Squibb, Drug Safety Evaluat, New Brunswick, NJ USA.
[Stewart, Jane] AstraZeneca, Drug Safety & Metab, Macclesfield, Cheshire, England.
[Weinbauer, Gerhard F.] Covance Preclin Serv GmbH, Munster, Germany.
[Wood, Sandra] Merck Res Labs, Upper Gwynedd, PA USA.
[Piersma, Aldert H.] Univ Utrecht, Inst Risk Assessment Sci, Fac Vet Sci, Utrecht, Netherlands.
RP Theunissen, PT (reprint author), Med Evaluat Board, Graadt van Roggenweg 500, NL-3531 AH Utrecht, Netherlands.
EM P.Theunissen@cbg-meb.nl
FU SLIM project; Dutch Government, Dept. Econimical Affairs; Utrecht
Province; Utrecht City Administration [PID101063]
FX SLIM project, by the Dutch Government, Dept. Econimical Affairs; The
Utrecht Province and The Utrecht City Administration [PID101063]. ILSI
HESI, 10.13039/100008663
NR 22
TC 0
Z9 0
U1 5
U2 5
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1040-8444
EI 1547-6898
J9 CRIT REV TOXICOL
JI Crit. Rev. Toxicol.
PY 2016
VL 46
IS 10
BP 900
EP 910
DI 10.1080/10408444.2016.1224807
PG 11
WC Toxicology
SC Toxicology
GA ED3CF
UT WOS:000388726200004
PM 27848393
ER
PT J
AU Blumenthal, GM
Mansfield, E
Pazdur, R
AF Blumenthal, Gideon M.
Mansfield, Elizabeth
Pazdur, Richard
TI Next-Generation Sequencing in Oncology in the Era of Precision Medicine
SO JAMA ONCOLOGY
LA English
DT Editorial Material
ID FDA
C1 [Blumenthal, Gideon M.; Pazdur, Richard] US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA.
[Mansfield, Elizabeth] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Blumenthal, GM (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA.
EM gideon.blumenthal@fda.hhs.gov
NR 6
TC 7
Z9 7
U1 1
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2374-2445
J9 JAMA ONCOL
JI JAMA Oncol.
PD JAN
PY 2016
VL 2
IS 1
BP 13
EP 14
DI 10.1001/jamaoncol.2015.4503
PG 2
WC Oncology
SC Oncology
GA DW5JE
UT WOS:000383679300002
PM 26540172
ER
PT J
AU Kazandjian, D
Khozin, S
Blumenthal, G
Zhang, LJ
Tang, SH
Libeg, M
Kluetz, P
Sridhara, R
Keegan, P
Pazdur, R
AF Kazandjian, Dickran
Khozin, Sean
Blumenthal, Gideon
Zhang, Lijun
Tang, Shenghui
Libeg, Meredith
Kluetz, Paul
Sridhara, Rajeshwari
Keegan, Patricia
Pazdur, Richard
TI Benefit-Risk Summary of Nivolumab for Patients With Metastatic Squamous
Cell Lung Cancer After Platinum-Based Chemotherapy A Report From the US
Food and Drug Administration
SO JAMA ONCOLOGY
LA English
DT Article
ID TRIAL; GUIDELINE; MUTATIONS; THERAPIES; DOCETAXEL; ERLOTINIB; ALK
AB IMPORTANCE Metastatic squamous non-small-cell lung cancer (SQ NSCLC) is a serious and life-threatening malignant condition with unmet medical need. In late December 2014, the US Food and Drug Administration (FDA) obtained the data monitoring committee report of a planned interim analysis of a trial in second-line SQ NSCLC (CM017) that demonstrated an overall survival benefit for patients treated with nivolumab compared with docetaxel.
OBSERVATIONS In that trial, 272 patients with metastatic SQ NSCLC patients had been randomized to receive nivolumab (n = 135) or docetaxel (n = 137). Median overall survival was 9.2 months for patients randomized to nivolumab and 6.0 months for those randomized to docetaxel (hazard ratio, 0.59; 95% CI, 0.44-0.79; P <.001). The safety of nivolumab was evaluated in a single-arm trial of 117 patients in previously treated metastatic SQ NSCLC and was consistent with the safety profile in melanoma, with rare but serious immune-mediated adverse events managed with corticosteroids and dose interruption.
CONCLUSIONS AND RELEVANCE The FDA granted nivolumab traditional approval on March 4, 2015, for treatment of metastatic SQ NSCLC with progression during or after platinum-based chemotherapy. The approval provides an important treatment option for these patients, affecting routine care and clinical trials.
C1 [Kazandjian, Dickran; Khozin, Sean; Blumenthal, Gideon; Libeg, Meredith; Kluetz, Paul; Keegan, Patricia; Pazdur, Richard] USDA, Off Hematol & Oncol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Zhang, Lijun; Tang, Shenghui; Sridhara, Rajeshwari] USDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Kazandjian, D (reprint author), USDA, Off Hematol Oncol Prod, 10903 New Hampshire Ave NE,WO22 2320, Silver Spring, MD 20993 USA.
EM Dickran.kazandjian@fda.hhs.gov
NR 21
TC 9
Z9 10
U1 2
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2374-2445
J9 JAMA ONCOL
JI JAMA Oncol.
PD JAN
PY 2016
VL 2
IS 1
BP 118
EP 122
DI 10.1001/jamaoncol.2015.3934
PG 5
WC Oncology
SC Oncology
GA DW5JE
UT WOS:000383679300024
PM 26470053
ER
PT J
AU Liu, AY
Yue, LQ
AF Liu, Aiyi
Yue, Lilly Q.
TI A conversation with Dr. Greg Campbell
SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS
LA English
DT Editorial Material
C1 [Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, Bethesda, MD USA.
[Yue, Lilly Q.] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, 10903 New Hampshire, Silver Spring, MD 20993 USA.
RP Yue, LQ (reprint author), US FDA, Div Biostat, Ctr Devices & Radiol Hlth, 10903 New Hampshire, Silver Spring, MD 20993 USA.
EM lilly.yue@fda.hhs.gov
OI Liu, Aiyi/0000-0002-6618-5082
NR 0
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1054-3406
EI 1520-5711
J9 J BIOPHARM STAT
JI J. Biopharm. Stat.
PY 2016
VL 26
IS 6
SI SI
BP 1007
EP 1019
DI 10.1080/10543406.2016.1226331
PG 13
WC Pharmacology & Pharmacy; Statistics & Probability
SC Pharmacology & Pharmacy; Mathematics
GA ED1HS
UT WOS:000388596600001
PM 27548092
ER
PT J
AU Gamalo-Siebers, M
Tiwari, R
LaVange, L
AF Gamalo-Siebers, Margaret
Tiwari, Ram
LaVange, Lisa
TI Flexible shrinkage estimation of subgroup effects through Dirichlet
process priors
SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS
LA English
DT Article
DE Dirichlet process prior; exchangeability; heterogeneity; model
selection; shrinkage; subgroups
ID CLINICAL-TRIAL DESIGNS; NONPARAMETRIC PROBLEMS; BAYESIAN-ANALYSIS;
MODEL; DISTRIBUTIONS
AB The paradigm shift towards precision medicine reignited interest in determining whether there are differential treatment effects in subgroups of trial participants. Intrinsic to this problem is that any assessment of a differential treatment effect is predicated on being able to estimate the treatment response accurately while satisfying constraints of balancing the risk of overlooking an important subgroup with the potential to make a decision based on a false discovery. While shrinkage models have been widely used to improve accuracy of subgroup parameter estimates by leveraging the relationship between them, there is still a possibility that it can lead to excessively conservative or anti-conservative results. This can possibly be due to the use of the normal distribution as prior, which forces outlying subjects to have their means over-shrunk towards the population mean, and the data from such subjects may be excessively influential in estimation of both the overall mean response and the mean response for each subgroup, or a model misspecification due to unaccounted variation or clustering. To address this issue, we investigate the use of nonparametric Bayes, particularly Dirichlet process priors, to create a flexible shrinkage model. This model represents uncertainty in the prior distribution for the overall response while accommodating heterogeneity among individual subgroups. We simulated data to compare estimates when there is no differential subgroup effect and when there is a differential subgroup effect. In either of these scenarios, the flexible shrinkage model does not force estimates to shrink excessively when similarity of treatment effects is not supported but still retains the attractiveness of improved precision given by the narrower credible intervals. We also applied the same method to a dataset based on trials conducted for an antimicrobial therapy on several related indications.
C1 [Gamalo-Siebers, Margaret] Eli Lilly & Co, 893 S Delaware St, Indianapolis, IN 46285 USA.
[Tiwari, Ram; LaVange, Lisa] US FDA, Ctr Drug Evaluat & Res, Off Biostat, Silver Spring, MD USA.
RP Gamalo-Siebers, M (reprint author), Eli Lilly & Co, 893 S Delaware St, Indianapolis, IN 46285 USA.
EM gamalo_margaret@lilly.com
NR 35
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1054-3406
EI 1520-5711
J9 J BIOPHARM STAT
JI J. Biopharm. Stat.
PY 2016
VL 26
IS 6
SI SI
BP 1040
EP 1055
DI 10.1080/10543406.2016.1226327
PG 16
WC Pharmacology & Pharmacy; Statistics & Probability
SC Pharmacology & Pharmacy; Mathematics
GA ED1HS
UT WOS:000388596600004
PM 27548701
ER
PT J
AU Li, JX
Chen, WC
Scott, JA
AF Li, Judy X.
Chen, Wei-Chen
Scott, John A.
TI Addressing prior-data conflict with empirical meta-analytic-predictive
priors in clinical studies with historical information
SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS
LA English
DT Article
DE Bayesian method; historical information; prior-data conflict; safety
study
ID SEVERE HEMOPHILIA-A; FACTOR-VIII PRODUCTS; EFFECTIVE SAMPLE-SIZE;
INHIBITOR DEVELOPMENT; TRIALS; MODELS; RECOMBINANT
AB A common question in clinical studies is how to use historical data from earlier studies, leveraging relevant information into the design and analysis of a new study. Bayesian approaches are particularly well-suited to this task, with their natural ability to borrow strength across data sources. In this paper, we propose an eMAP approach for incorporating historical data into the analysis of clinical studies, and we discuss an application of this method to the analysis of observational safety studies for a class of products for patients with hemophilia A. The eMAP prior approach is flexible and robust to prior-data conflict. We conducted simulations to compare the frequentist operating characteristics of three approaches under different prior-data conflict assumptions and sample size scenarios.
C1 [Li, Judy X.] OBE, FDA CBER, 10903 New Hampshire Ave,Bldg 71, Silver Spring, MD 20993 USA.
[Chen, Wei-Chen] OBE DB, FDA CBER, Silver Spring, MD USA.
[Scott, John A.] CBER, FDA, Rockville, MD USA.
RP Li, JX (reprint author), OBE, FDA CBER, 10903 New Hampshire Ave,Bldg 71, Silver Spring, MD 20993 USA.
EM judy.li@fda.hhs.gov
FU FDA Office of Women's Health; U.S. Department of Energy; FDA/CBER
FX This work was supported by the FDA Office of Women's Health. This
project was supported in part by an appointment to the ORISE Research
Participation Program at the Center for Biologics Evaluation and
Research, U.S. Food and Drug Administration, administered by the Oak
Ridge Institute for Science and Education through an interagency
agreement between the U.S. Department of Energy and FDA/CBER. This work
used the computational resources of the HPC clusters at the U.S. Food
and Drug Administration, Center for Devices and Radiological Health
(CDRH).
NR 30
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1054-3406
EI 1520-5711
J9 J BIOPHARM STAT
JI J. Biopharm. Stat.
PY 2016
VL 26
IS 6
SI SI
BP 1056
EP 1066
DI 10.1080/10543406.2016.1226324
PG 11
WC Pharmacology & Pharmacy; Statistics & Probability
SC Pharmacology & Pharmacy; Mathematics
GA ED1HS
UT WOS:000388596600005
PM 27541990
ER
PT J
AU Yu, TH
Li, Q
Gray, G
Yue, LQ
AF Yu, Tinghui
Li, Qin
Gray, Gerry
Yue, Lilly Q.
TI Statistical innovations in diagnostic device evaluation
SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS
LA English
DT Article
DE Biomarker; bootstrap; companion diagnostics; missing data; MRMC studies;
ROC
ID COMPUTER-AIDED DETECTION; CLINICAL-TRIAL DESIGNS; VALIDATION; BIOMARKER;
MEDICINE; READERS; FDA
AB Due to rapid technological development, innovations in diagnostic devices are proceeding at an extremely fast pace. Accordingly, the needs for adopting innovative statistical methods have emerged in the evaluation of diagnostic devices. Statisticians in the Center for Devices and Radiological Health at the Food and Drug Administration have provided leadership in implementing statistical innovations. The innovations discussed in this article include: the adoption of bootstrap and Jackknife methods, the implementation of appropriate multiple reader multiple case study design, the application of robustness analyses for missing data, and the development of study designs and data analyses for companion diagnostics.
C1 [Yu, Tinghui; Li, Qin; Gray, Gerry; Yue, Lilly Q.] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
RP Yue, LQ (reprint author), US FDA, Div Biostat, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM lilly.yue@fda.hhs.gov
NR 42
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1054-3406
EI 1520-5711
J9 J BIOPHARM STAT
JI J. Biopharm. Stat.
PY 2016
VL 26
IS 6
SI SI
BP 1067
EP 1077
DI 10.1080/10543406.2016.1226332
PG 11
WC Pharmacology & Pharmacy; Statistics & Probability
SC Pharmacology & Pharmacy; Mathematics
GA ED1HS
UT WOS:000388596600006
PM 27541859
ER
PT J
AU Pennello, G
Pantoja-Galicia, N
Evans, S
AF Pennello, Gene
Pantoja-Galicia, Norberto
Evans, Scott
TI Comparing diagnostic tests on benefit-risk
SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS
LA English
DT Article
DE Clinical utility; cost; benefit ratio; decision theory; diagnostic
yield; relative net benefit; risk threshold; weighted accuracy
ID RELATIVE UTILITY CURVES; CLINICAL-TRIAL DESIGNS; PREDICTION; BIOMARKERS;
MODELS; MARKER; PHASE
AB Comparing diagnostic tests on accuracy alone can be inconclusive. For example, a test may have better sensitivity than another test yet worse specificity. Comparing tests on benefit risk may be more conclusive because clinical consequences of diagnostic error are considered. For benefit-risk evaluation, we propose diagnostic yield, the expected distribution of subjects with true positive, false positive, true negative, and false negative test results in a hypothetical population. We construct a table of diagnostic yield that includes the number of false positive subjects experiencing adverse consequences from unnecessary work-up. We then develop a decision theory for evaluating tests. The theory provides additional interpretation to quantities in the diagnostic yield table. It also indicates that the expected utility of a test relative to a perfect test is a weighted accuracy measure, the average of sensitivity and specificity weighted for prevalence and relative importance of false positive and false negative testing errors, also interpretable as the cost-benefit ratio of treating non-diseased and diseased subjects. We propose plots of diagnostic yield, weighted accuracy, and relative net benefit of tests as functions of prevalence or cost-benefit ratio. Concepts are illustrated with hypothetical screening tests for colorectal cancer with test positive subjects being referred to colonoscopy.
C1 [Pennello, Gene; Pantoja-Galicia, Norberto] US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
[Evans, Scott] Harvard T H Chan Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA USA.
[Evans, Scott] Harvard T H Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA.
RP Pennello, G (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM gene.pennello@fda.hhs.gov
FU National Institute of Allergy And Infectious Diseases of the National
Institutes of Health [UM1AI104681]
FX Research reported in this publication was supported by the National
Institute of Allergy And Infectious Diseases of the National Institutes
of Health under Award Number UM1AI104681. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health.
NR 22
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U1 2
U2 2
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1054-3406
EI 1520-5711
J9 J BIOPHARM STAT
JI J. Biopharm. Stat.
PY 2016
VL 26
IS 6
SI SI
BP 1083
EP 1097
DI 10.1080/10543406.2016.1226335
PG 15
WC Pharmacology & Pharmacy; Statistics & Probability
SC Pharmacology & Pharmacy; Mathematics
GA ED1HS
UT WOS:000388596600008
PM 27548805
ER
PT J
AU Zhang, ZW
Chu, JX
Rahardja, D
Zhang, H
Tang, L
AF Zhang, Zhiwei
Chu, Jianxiong
Rahardja, Dewi
Zhang, Hui
Tang, Li
TI Responder analysis without dichotomization
SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS
LA English
DT Article
DE Clinical trial; delta method; efficiency; information bound; missing
data; robustness
AB In clinical trials, it is common practice to categorize subjects as responders and non-responders on the basis of one or more clinical measurements under pre-specified rules. Such a responder analysis is often criticized for the loss of information in dichotomizing one or more continuous or ordinal variables. It is worth noting that a responder analysis can be performed without dichotomization, because the proportion of responders for each treatment can be derived from a model for the original clinical variables (used to define a responder) and estimated by substituting maximum likelihood estimators of model parameters. This model-based approach can be considerably more efficient and more effective for dealing with missing data than the usual approach based on dichotomization. For parameter estimation, the model-based approach generally requires correct specification of the model for the original variables. However, under the sharp null hypothesis, the model-based approach remains unbiased for estimating the treatment difference even if the model is misspecified. We elaborate on these points and illustrate them with a series of simulation studies mimicking a study of Parkinson's disease, which involves longitudinal continuous data in the definition of a responder.
C1 [Zhang, Zhiwei] Univ Calif Riverside, Dept Stat, Riverside, CA 92521 USA.
[Chu, Jianxiong] US FDA, Ctr Devices & Radiol Hlth, Div Biostat, Off Surveillance & Biomet, Silver Spring, MD USA.
[Rahardja, Dewi] US Dept Def, Ft George G Meade, MD USA.
[Zhang, Hui; Tang, Li] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN USA.
RP Zhang, ZW (reprint author), Univ Calif Riverside, Dept Stat, Riverside, CA 92521 USA.
EM zhiwei.zhang@ucr.edu
NR 15
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1054-3406
EI 1520-5711
J9 J BIOPHARM STAT
JI J. Biopharm. Stat.
PY 2016
VL 26
IS 6
SI SI
BP 1125
EP 1135
DI 10.1080/10543406.2016.1226325
PG 11
WC Pharmacology & Pharmacy; Statistics & Probability
SC Pharmacology & Pharmacy; Mathematics
GA ED1HS
UT WOS:000388596600012
PM 27540771
ER
PT J
AU Yue, LQ
Campbell, G
Lu, N
Xu, YL
Zuckerman, B
AF Yue, Lilly Q.
Campbell, Gregory
Lu, Nelson
Xu, Yunling
Zuckerman, Bram
TI Utilizing national and international registries to enhance pre-market
medical device regulatory evaluation
SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS
LA English
DT Article
DE Data quality; observational comparative studies; propensity score;
registry; study design
ID PROPENSITY SCORE; CAUSAL INFERENCE; DESIGN; BIAS
AB Regulatory decisions are made based on the assessment of risk and benefit of medical devices at the time of pre-market approval and subsequently, when post-market risk-benefit balance needs reevaluation. Such assessments depend on scientific evidence obtained from pre-market studies, post-approval studies, post-market surveillance studies, patient perspective information, as well as other real world data such as national and international registries. Such registries provide real world evidence and are playing a more and more important role in enhancing the safety and effectiveness evaluation of medical devices. While these registries provide large quantities of data reflecting real world practice and can potentially reduce the cost of clinical trials, challenges arise concerning (1) data quality adequate for regulatory decision-making, (2) bias introduced at every stage and aspect of study, (3) scientific validity of study designs, and (4) reliability and interpretability of study results. This article will discuss related statistical and regulatory challenges and opportunities with examples encountered in medical device regulatory reviews.
C1 [Yue, Lilly Q.; Campbell, Gregory; Lu, Nelson; Xu, Yunling] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
[Zuckerman, Bram] US FDA, Div Cardiovasc Devices, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Yue, LQ (reprint author), US FDA, Div Biostat, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM lilly.yue@fda.hhs.gov
NR 17
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1054-3406
EI 1520-5711
J9 J BIOPHARM STAT
JI J. Biopharm. Stat.
PY 2016
VL 26
IS 6
SI SI
BP 1136
EP 1145
DI 10.1080/10543406.2016.1226336
PG 10
WC Pharmacology & Pharmacy; Statistics & Probability
SC Pharmacology & Pharmacy; Mathematics
GA ED1HS
UT WOS:000388596600013
PM 27540636
ER
PT J
AU Megget, K
AF Megget, Katrina
TI cleaner hands
SO CHEMISTRY & INDUSTRY
LA English
DT Article
C1 [Megget, Katrina] US FDA, Rockville, MD 20857 USA.
RP Megget, K (reprint author), US FDA, Rockville, MD 20857 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY PERIODICALS, INC
PI SAN FRANCISCO
PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA
SN 0009-3068
EI 2047-6329
J9 CHEM IND-LONDON
JI Chem. Ind.
PY 2016
VL 80
IS 9
BP 30
EP 32
PG 3
WC Chemistry, Applied
SC Chemistry
GA EC8WP
UT WOS:000388424100020
ER
PT B
AU Sharma, M
Ingram, D
Graham, L
AF Sharma, Manan
Ingram, David
Graham, Lorna
BE Soon, JM
Manning, L
Wallace, CA
TI Foodborne Outbreaks and Potential Routes of Contamination in Fresh and
Fresh-Cut Fruits and Vegetables
SO FOODBORNE DISEASES: CASE STUDIES OF OUTBREAKS IN THE AGRI-FOOD
INDUSTRIES
LA English
DT Article; Book Chapter
ID ESCHERICHIA-COLI O157-H7; UNPASTEURIZED ORANGE JUICE; UNITED-STATES;
TYPHOID-FEVER; MULTISTATE OUTBREAK; SALMONELLA-POONA; CANTALOUPE RIND;
SURVIVAL; WATERMELON; INFECTION
C1 [Sharma, Manan] ARS, USDA, Beltsville, MD 20705 USA.
[Ingram, David] US FDA, Div Produce Safety, College Pk, MD USA.
[Graham, Lorna] Univ Maryland Eastern Shore, Dept Agr, Princess Anne, MD USA.
RP Sharma, M (reprint author), ARS, USDA, Beltsville, MD 20705 USA.
NR 68
TC 0
Z9 0
U1 0
U2 0
PU CRC PRESS-TAYLOR & FRANCIS GROUP
PI BOCA RATON
PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA
BN 978-1-4822-0828-3; 978-1-4822-0827-6
PY 2016
BP 19
EP 36
D2 10.1201/b19463
PG 18
WC Biotechnology & Applied Microbiology; Food Science & Technology;
Microbiology
SC Biotechnology & Applied Microbiology; Food Science & Technology;
Microbiology
GA BG3WN
UT WOS:000388323700004
ER
PT S
AU Ghassemi, P
Wang, QZ
Pfefer, TJ
AF Ghassemi, Pejhman
Wang, Quanzeng
Pfefer, T. Joshua
BE Raghavachari, R
Liang, R
TI Dynamic thermal effects of epidermal melanin and plasmonic nanoparticles
during photoacoustic breast imaging
SO DESIGN AND QUALITY FOR BIOMEDICAL TECHNOLOGIES IX
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Design and Quality for Biomedical Technologies IX
CY FEB 13-14, 2016
CL San Francisco, CA
SP SPIE
DE melanin; plasmonic nanoparticles; photothermal safety; photoacoustic
tomography; thermal imaging
ID PORT-WINE STAINS; OPTICAL-PROPERTIES; LASER TREATMENT; GOLD NANORODS;
HUMAN SKIN; TISSUE; SPECTROSCOPY; MICE
AB Photoacoustic Tomography (PAT) employs high-power near-infrared (near-IR) laser pulses to generate structural and functional information on tissue chromophores up to several centimeters below the surface. Such insights may facilitate detection of breast cancer - the most common cancer in women. PAT mammography has been the subject of extensive research, including techniques based on exogenous agents for PAT contrast enhancement and molecular specificity. However, photothermal safety risks of PAT due to strong chromophores such as epidermal melanin and plasmonic nanoparticles have not been rigorously studied. We have used computational and experimental approaches to elucidate highly dynamic optical-thermal processes during PAT. A Monte Carlo model was used to simulate light propagation at 800 and 1064 nm in a multi-layer breast tissue geometry with different epidermal pigmentation levels and a tumor-simulating inclusion incorporating nanoparticles. Energy deposition results were then used in a bioheat transfer model to simulate temperature transients. Experimental measurements involved multi-layer hydrogel phantoms with inclusions incorporating gold nanoparticles. Phantom optical properties were measured using the inverse adding-doubling technique. Thermal imaging was performed as phantoms were irradiated with 5 ns near-IR pulses. Scenarios using 10 Hz laser irradiation of breast tissue containing various nanoparticle concentrations were implemented experimentally and computationally. Laser exposure levels were based on ANSI/IEC limits. Surface temperature measurements were compared to corresponding simulation data. In general, the effect of highly pigmented skin on temperature rise was significant, whereas unexpectedly small levels of temperature rise during nanoparticle irradiation were attributed to rapid photodegradation. Results provide key initial insights into light-tissue interactions impacting the safety and effectiveness of PAT.
C1 [Ghassemi, Pejhman; Wang, Quanzeng; Pfefer, T. Joshua] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
RP Pfefer, TJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
EM Joshua.Pfefer@fda.hhs.gov
NR 31
TC 0
Z9 0
U1 0
U2 0
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-62841-934-4
J9 PROC SPIE
PY 2016
VL 9700
AR 97000F
DI 10.1117/12.2214870
PG 9
WC Physics, Applied; Imaging Science & Photographic Technology; Radiology,
Nuclear Medicine & Medical Imaging
SC Physics; Imaging Science & Photographic Technology; Radiology, Nuclear
Medicine & Medical Imaging
GA BF6RL
UT WOS:000383614900014
ER
PT S
AU Wang, BH
Ghassemi, P
Wang, JT
Wang, QZ
Chen, Y
Pfefer, J
AF Wang, Bohan
Ghassemi, Pejhman
Wang, Jianting
Wang, Quanzeng
Chen, Yu
Pfefer, Joshua
BE Raghavachari, R
Liang, R
TI Performance Evaluation of CCD- and Mobile-Phone-Based Near-Infrared
Fluorescence Imaging Systems with Molded and 3D-Printed Phantoms
SO DESIGN AND QUALITY FOR BIOMEDICAL TECHNOLOGIES IX
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Design and Quality for Biomedical Technologies IX
CY FEB 13-14, 2016
CL San Francisco, CA
SP SPIE
DE Near infrared fluorescence; Performance testing; Mobile phone; 3D
printing; Tissue phantoms
AB Increasing numbers of devices are emerging which involve biophotonic imaging on a mobile platform. Therefore, effective test methods are needed to ensure that these devices provide a high level of image quality. We have developed novel phantoms for performance assessment of near infrared fluorescence (NIRF) imaging devices. Resin molding and 3D printing techniques were applied for phantom fabrication. Comparisons between two imaging approaches - a CCD-based scientific camera and an NIR-enabled mobile phone - were made based on evaluation of the contrast transfer function and penetration depth. Optical properties of the phantoms were evaluated, including absorption and scattering spectra and fluorescence excitation-emission matrices. The potential viability of contrast-enhanced biological NIRF imaging with a mobile phone is demonstrated, and color-channel-specific variations in image quality are documented. Our results provide evidence of the utility of novel phantom-based test methods for quantifying image quality in emerging NIRF devices.
C1 [Wang, Bohan; Chen, Yu] Univ Maryland, Dept Bioengn, College Pk, MD 20742 USA.
[Wang, Bohan; Ghassemi, Pejhman; Wang, Jianting; Wang, Quanzeng; Pfefer, Joshua] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
RP Wang, BH (reprint author), Univ Maryland, Dept Bioengn, College Pk, MD 20742 USA.; Wang, BH (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
NR 14
TC 0
Z9 0
U1 0
U2 0
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-62841-934-4
J9 PROC SPIE
PY 2016
VL 9700
AR 970006
DI 10.1117/12.2220412
PG 8
WC Physics, Applied; Imaging Science & Photographic Technology; Radiology,
Nuclear Medicine & Medical Imaging
SC Physics; Imaging Science & Photographic Technology; Radiology, Nuclear
Medicine & Medical Imaging
GA BF6RL
UT WOS:000383614900005
ER
PT S
AU Wang, JT
Chen, Y
Pfefer, J
AF Wang, Jianting
Chen, Yu
Pfefer, Joshua
BE Raghavachari, R
Liang, R
TI Quantitative Assessment Of Hyperspectral Imaging In Detection Of
Plasmonic Nanoparticles - A Modified Contrast-detail Analysis Approach
SO DESIGN AND QUALITY FOR BIOMEDICAL TECHNOLOGIES IX
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Design and Quality for Biomedical Technologies IX
CY FEB 13-14, 2016
CL San Francisco, CA
SP SPIE
DE Hyperspectral imaging; contrast-detail analysis; standardized test
method; tissue phantom
ID OPTICAL-PROPERTIES; TURBID MEDIA; GOLD NANORODS; TOMOGRAPHY;
REFLECTANCE; TISSUES
AB Hyperspectral reflectance imaging (HRI) is an emerging imaging modality being applied for clinical indications such as tissue oximetry, and cancer detection based on endogenous biological constituents including plasmonic nanoparticles. However, there is currently a lack of standardized test methods for objective, quantitative evaluation of HRI system performance. Contrast-detail analysis (CDA) is a phantom-based test method commonly used to evaluate medical imaging devices (e.g., mammography systems) in terms of their lower detection limit. We investigated a modified CDA (mCDA) method to quantify the detectability of gold nanoparticles by HRI systems. Silicone-based turbid phantoms containing micro-fluidic channels were developed for the mCDA tests. Polydimethylsiloxane (PDMS) phantom materials were doped with chromophores and scatterers to achieve biologically relevant optical properties (OPs). Molds were used to produce cylindrical channels of diameters 0.3 to 1.65 mm and depths of 0.2 mm inside the phantoms. Channels were filled with a mixture of hemoglobin and concentrations of gold nanorods (GNR) and measured with our HRI system. The contrast of GNRs was solved with a spectral unmixing algorithm from the reflectance spectra. The lowest detectable concentration was determined as a function of inclusion size and depth and plotted as modified contrast detail curve (mCDC). mCDCs were used to compare the detectabilities of the HRI system with different data processing algorithms. It is demonstrated that our mCDA test method involving turbid microchannel phantoms can help to elucidate the combined performance of imaging devices and plasmonic nanoparticle contrast agents. This approach may be useful for performing clinical trial standardization and device re-calibration, thus ensuring quality control and clinical performance.
C1 [Wang, Jianting; Pfefer, Joshua] US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20093 USA.
[Chen, Yu] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA.
RP Pfefer, J (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20093 USA.
EM Joshua.Pfefer@fda.hhs.gov
NR 30
TC 0
Z9 0
U1 1
U2 1
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-62841-934-4
J9 PROC SPIE
PY 2016
VL 9700
AR 97000D
DI 10.1117/12.2214750
PG 8
WC Physics, Applied; Imaging Science & Photographic Technology; Radiology,
Nuclear Medicine & Medical Imaging
SC Physics; Imaging Science & Photographic Technology; Radiology, Nuclear
Medicine & Medical Imaging
GA BF6RL
UT WOS:000383614900012
ER
PT S
AU Hong, HX
Chen, MJ
Ng, HW
Tong, WD
AF Hong, Huixiao
Chen, Minjun
Ng, Hui Wen
Tong, Weida
BE Benfenati, E
TI QSAR Models at the US FDA/NCTR
SO IN SILICO METHODS FOR PREDICTING DRUG TOXICITY
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE FDA; Databases; Liver toxicity; Endocrine disruptors
ID INDUCED LIVER-INJURY; ENDOCRINE DISRUPTING CHEMICALS; HIV-1 INTEGRASE
INHIBITORS; ESTROGEN-RECEPTOR BINDING; DENSITY-FUNCTIONAL THEORY;
DECISION FOREST; MOLECULAR DOCKING; STRUCTURAL DESCRIPTORS;
ENVIRONMENTAL CHEMICALS; CYTOCHROME-P450 CYP3A4
AB Quantitative structure-activity relationship (QSAR) has been used in the scientific research community for many decades and applied to drug discovery and development in the industry. QSAR technologies are advancing fast and attracting possible applications in regulatory science. To facilitate the development of reliable QSAR models, the FDA had invested a lot of efforts in constructing chemical databases with a variety of efficacy and safety endpoint data, as well as in the development of computational algorithms. In this chapter, we briefly describe some of the often used databases developed at the FDA such as EDKB (Endocrine Disruptor Knowledge Base), EADB (Estrogenic Activity Database), LTKB (Liver Toxicity Knowledge Base), and CERES (Chemical Evaluation and Risk Estimation System) and the technologies adopted by the agency such as Mold2 program for calculation of a large and diverse set of molecular descriptors and decision forest algorithm for QSAR model development. We also summarize some QSAR models that have been developed for safety evaluation of the FDA-regulated products.
C1 [Hong, Huixiao; Chen, Minjun; Ng, Hui Wen; Tong, Weida] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Hong, HX (reprint author), US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
NR 67
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES
SN 1064-3745
BN 978-1-4939-3609-0; 978-1-4939-3607-6
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2016
VL 1425
BP 431
EP 459
DI 10.1007/978-1-4939-3609-0_18
D2 10.1007/978-1-4939-3609-0
PG 29
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA BG2YT
UT WOS:000387782000019
PM 27311476
ER
PT J
AU Zhao, XQ
Alexander, TN
Hoffman, L
Jones, C
Delahanty, J
Walker, M
Berger, AT
Talbert, E
AF Zhao, Xiaoquan
Alexander, Tesfa N.
Hoffman, Leah
Jones, Chaunetta
Delahanty, Janine
Walker, Matthew
Berger, Amanda T.
Talbert, Emily
TI Youth Receptivity to FDA's The Real Cost Tobacco Prevention Campaign:
Evidence From Message Pretesting
SO JOURNAL OF HEALTH COMMUNICATION
LA English
DT Article
ID CESSATION MEDIA MESSAGES; PLANNED BEHAVIOR; SMOKING-CESSATION; EXTENDED
VERSION; ADOLESCENTS; SMOKERS; IMPACT
AB In February 2014, the Food and Drug Administration launched The Real Cost, a national youth tobacco prevention campaign. This article examines youth receptivity to potential campaign ads using data from 3 message pretesting studies featuring the same design and consistent instrumentation. A total of 3,258 adolescents ages 13-17 were randomized to either an ad-viewing condition or a no-exposure control condition. Perceived ad effectiveness, smoking-related beliefs, and attitudes were measured as outcome variables. The sample consisted of both experimental smokers (58%) and current nonsmokers at risk for cigarette initiation (42%). A total of 14 ads were tested across the three studies. Participants who viewed the ads generally considered them to be effective (with a mean perceived ad effectiveness score of 3.66 on a scale from 1 to 5). Compared to those in the control condition, participants in the ad-viewing condition reported stronger beliefs about the health risks of smoking (p<.001), a greater likelihood that smoking would lead to loss of control in life (p<.001), and more negative attitudes toward smoking (p<.001). Responses to campaign ads were largely consistent between experimenters and at-risk nonsmokers. Implications of the findings for the campaign are discussed.
C1 [Zhao, Xiaoquan; Alexander, Tesfa N.; Hoffman, Leah; Jones, Chaunetta; Delahanty, Janine; Talbert, Emily] US FDA, Ctr Tobacco Prod, Silver Spring, MD USA.
[Zhao, Xiaoquan] George Mason Univ, Dept Commun, MS3D6,4400 Univ Dr, Fairfax, VA 22030 USA.
[Walker, Matthew; Berger, Amanda T.] Natl Acad Med, FDA Tobacco Regulatory Sci Fellowship, Washington, DC USA.
RP Zhao, XQ (reprint author), George Mason Univ, Dept Commun, MS3D6,4400 Univ Dr, Fairfax, VA 22030 USA.
EM xzhao3@gmu.edu
FU Intramural FDA HHS [FD999999]
NR 32
TC 0
Z9 0
U1 4
U2 4
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1081-0730
EI 1087-0415
J9 J HEALTH COMMUN
JI J. Health Commun.
PY 2016
VL 21
IS 11
BP 1153
EP 1160
DI 10.1080/10810730.2016.1233307
PG 8
WC Communication; Information Science & Library Science
SC Communication; Information Science & Library Science
GA EC3LW
UT WOS:000388028600004
PM 27736365
ER
PT J
AU Rupert, DJ
Read, JG
Amoozegar, JB
Moultrie, RR
Taylor, OM
O'Donoghue, AC
Sullivan, HW
AF Rupert, Douglas J.
Read, Jennifer Gard
Amoozegar, Jacqueline B.
Moultrie, Rebecca R.
Taylor, Olivia M.
O'Donoghue, Amie C.
Sullivan, Helen W.
TI Peer-Generated Health Information: The Role of Online Communities in
Patient and Caregiver Health Decisions
SO JOURNAL OF HEALTH COMMUNICATION
LA English
DT Article
ID SOCIAL NETWORKS; INTERNET USE; NATIONAL-SURVEY; CANCER; CARE; SUPPORT;
CREDIBILITY; IMPACT; WEB; BENEFITS
AB Individuals increasingly access peer-generated health information (PGHI) through social media, especially online health communities (OHCs). Previous research has documented PGHI topics, credibility assessment strategies, and PGHI's connection with well-being. However, there is limited evidence on where, when, and why individuals seek PGHI and how they use PGHI in health decisions. We conducted in-person and online focus groups with verified OHC members (N=89)representing 50 different medical conditions and 77 OHCsto explore these topics. Two researchers independently coded transcripts with NVivo 9.2 and thematically analyzed responses. Most individuals accidentally discovered PGHI during Web searches rather than intentionally seeking it. Individuals valued PGHI primarily as an alternative information source about treatment options, self-care activities, and health care provider questions rather than a source of emotional support, and they acknowledged PGHI's limitation as anecdotal evidence. Individuals used PGHI as a springboard for additional research and patient-provider discussions, ultimately making treatment decisions alongside providers. These findings suggest that individuals use PGHI in much the same way they use traditional online health information and that PGHI facilitates, rather than obstructs, shared decision making with health care providers.
C1 [Rupert, Douglas J.; Read, Jennifer Gard; Moultrie, Rebecca R.; Taylor, Olivia M.] RTI Int, Ctr Commun Sci, 3040 Cornwallis Rd, Res Triangle Pk, NC 27709 USA.
[Amoozegar, Jacqueline B.] RTI Int, Social & Hlth Org Res & Evaluat Program, Res Triangle Pk, NC USA.
[O'Donoghue, Amie C.; Sullivan, Helen W.] US FDA, Ctr Drug Evaluat & Res, Off Prescript Drug Promot, Silver Spring, MD USA.
RP Rupert, DJ (reprint author), RTI Int, Ctr Commun Sci, 3040 Cornwallis Rd, Res Triangle Pk, NC 27709 USA.
EM drupert@rti.org
FU U.S. Food and Drug Administration, Office of Prescription Drug Promotion
FX This research was funded by a contract from the U.S. Food and Drug
Administration, Office of Prescription Drug Promotion. The findings and
conclusions in this article are our own and do not necessarily reflect
the opinions of the U.S. Food and Drug Administration.
NR 63
TC 0
Z9 0
U1 4
U2 4
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1081-0730
EI 1087-0415
J9 J HEALTH COMMUN
JI J. Health Commun.
PY 2016
VL 21
IS 11
BP 1187
EP 1197
DI 10.1080/10810730.2016.1237592
PG 11
WC Communication; Information Science & Library Science
SC Communication; Information Science & Library Science
GA EC3LW
UT WOS:000388028600008
PM 27805496
ER
PT J
AU Sullivan, HW
O'Donoghue, AC
Rupert, DJ
Willoughby, JF
Amoozegar, JB
Aikin, KJ
AF Sullivan, Helen W.
O'Donoghue, Amie C.
Rupert, Douglas J.
Willoughby, Jessica Fitts
Amoozegar, Jacqueline B.
Aikin, Kathryn J.
TI Are Disease Awareness Links on Prescription Drug Websites Misleading? A
Randomized Study
SO JOURNAL OF HEALTH COMMUNICATION
LA English
DT Article
ID HEALTH INFORMATION; ADVERTISING EXPOSURE; CONSUMER; PHYSICIANS;
ADVERTISEMENTS; CREDIBILITY; PERCEPTIONS; DISCLOSURES; EXPERIENCE;
CAPACITY
AB We sought to determine whether links from branded prescription drug websites to websites containing disease information mislead participants about drug benefits and whether nonsponsorship disclosures diminish this potential effect. We randomly assigned online panelists with depression (N=1,071) to view a fictitious prescription drug website that had (a) no link to a disease information website (control), (b) a link with no disclosure, (c) a link with a simple nonsponsorship disclosure, or (d) a link with a detailed nonsponsorship disclosure. If participants in the link conditions did not click the link, they were returned to the drug website and encouraged to click it. All participants then completed an online questionnaire assessing recall, perceptions, and intentions. Few participants (12%) clicked the link without prompting; 67% did so when prompted. Compared with control participants, participants in link conditions were more likely to confuse disease information with drug benefits and to recall fewer true drug benefits. Disclosures did not diminish these effects, and exposure to disease information did not affect other perceptions or intentions. Consumers seem to confuse information on disease websites with information on branded prescription drug websites. Disclosures may not adequately help consumers to distinguish between the 2 types of information.
C1 [Sullivan, Helen W.; O'Donoghue, Amie C.; Aikin, Kathryn J.] US FDA, Ctr Drug Evaluat & Res, Off Prescript Drug Promot, 10903 New Hampshire Ave,Bldg 51,Room 3238, Silver Spring, MD 20993 USA.
[Rupert, Douglas J.; Amoozegar, Jacqueline B.] RTI Int, Res Triangle Pk, NC USA.
[Willoughby, Jessica Fitts] Washington State Univ, Edward R Murrow Coll Commun, Pullman, WA 99164 USA.
RP Sullivan, HW (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Prescript Drug Promot, 10903 New Hampshire Ave,Bldg 51,Room 3238, Silver Spring, MD 20993 USA.
EM Helen.Sullivan@fda.hhs.gov
OI Willoughby, Jessica/0000-0002-1118-9502
FU Office of Prescription Drug Promotion, U.S. Food and Drug
Administration; RTI International
FX Funding was provided by the Office of Prescription Drug Promotion, U.S.
Food and Drug Administration, and data were collected through a contract
with RTI International. Jessica Fitts Willoughby was a contractor with
RTI International at the time this study was conducted.
NR 47
TC 0
Z9 0
U1 1
U2 1
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1081-0730
EI 1087-0415
J9 J HEALTH COMMUN
JI J. Health Commun.
PY 2016
VL 21
IS 11
BP 1198
EP 1207
DI 10.1080/10810730.2016.1237594
PG 10
WC Communication; Information Science & Library Science
SC Communication; Information Science & Library Science
GA EC3LW
UT WOS:000388028600009
PM 27805473
ER
PT B
AU Kweon, O
Kim, SJ
Sutherland, JB
Cerniglia, CE
AF Kweon, Ohgew
Kim, Seong-Jae
Sutherland, John B.
Cerniglia, Carl E.
BE Dlugonski, J
TI Novel Insights into Polycyclic Aromatic Hydrocarbon Biodegradation
Pathways Using Systems Biology and Bioinformatics Approaches
SO MICROBIAL BIODEGRADATION: FROM OMICS TO FUNCTION AND APPLICATION
LA English
DT Article; Book Chapter
ID MYCOBACTERIUM-VANBAALENII PYR-1; SP STRAIN PYR-1; PYRENE DEGRADATION;
METABOLIC NETWORK; MOLECULAR CHARACTERIZATION; FLUORANTHENE METABOLISM;
DEGRADING MYCOBACTERIA; CLASSIFICATION-SYSTEM; CATALASE-PEROXIDASE;
DIOXYGENASE GENES
AB Biodegradation of polycyclic aromatic hydrocarbons (PAHs) entails a complex and diverse set of biological reactions. Although there has been a massive effort over the years, understanding of the mechanism of PAH biodegradation has been limited when using the traditional approaches of genetics and biochemistry. The application of systems biology approaches, with advanced high-throughput analytical technologies, provides new global insights into not only the direct molecular mechanisms but also the genome-wide cellular ecophysiological responses involved in PAH degradation. This review describes research accomplishments from earlier traditional genetic and biochemical studies as well as the recent achievements of a combination of genomic, proteomic, and bioinformatics approaches to elucidate pathways for the degradation of high-molecular weight (HMW) PAHs.
C1 [Kweon, Ohgew; Kim, Seong-Jae; Sutherland, John B.; Cerniglia, Carl E.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Kweon, O (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
EM oh-gew.kweon@fda.hhs.gov; seong-jae.kim@fda.hhs.gov;
john.sutherland@fda.hhs.gov; carl.cemiglia@hhs.fda.gov
NR 87
TC 0
Z9 0
U1 2
U2 2
PU CAISTER ACADEMIC PRESS
PI WYMONDHAM
PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND
BN 978-1-910190-45-6
PY 2016
BP 143
EP 166
PG 24
WC Biotechnology & Applied Microbiology; Engineering, Environmental;
Microbiology
SC Biotechnology & Applied Microbiology; Engineering; Microbiology
GA BG3AW
UT WOS:000387832200009
ER
PT S
AU Zheng, JF
Li, DW
Chen, J
Kainz, W
AF Zheng, Jianfeng
Li, Dawei
Chen, Ji
Kainz, Wolfgang
GP IEEE
TI Numerical Study of SAR for Multi-Component Orthopaedic Hip Replacement
System During MRI
SO 2016 IEEE INTERNATIONAL SYMPOSIUM ON ELECTROMAGNETIC COMPATIBILITY (EMC)
SE IEEE International Symposium on Electromagnetic Compatibility
LA English
DT Proceedings Paper
CT IEEE International Symposium on Electromagnetic Compatibility (EMC)
CY JUL 25-29, 2016
CL Ottawa, CANADA
SP IEEE Electromagnet Compatibil Soc
DE RF heating; MRI; FDTD; Computational modeling
ID HUMAN HEAD; DEVICES
AB In this study we present numerical simulations of the Specific Absorption Rate (SAR) for multi-component orthopaedic hip replacement systems. The SAR is used to evaluate the radio frequency (RF)-induced heating of the devices during magnetic resonance imaging (MRI). Because multicomponent orthopaedic hip replacement systems have many combinations of components with various designs and sizes, it is computationally intensive, and almost impossible, to evaluate the SAR and the corresponding temperature rise for each possible combination and configuration. In this study, an effective searching strategy and a computational simulation model are developed to evaluate the factors associated with induced SAR in the tissue near an orthopaedic hip replacement system, and to find the "worst case" peak SAR for all possible combinations. The finite-difference time-domain (FDTD) was used to calculate the peak SAR for a typical hip replacement system inside the American Society for Testing and Materials (ASTM) phantom for both 1.5 Tesla (T) and 3T MRI systems. The results indicate that the stem and screw lengths are the most important factors influencing the peak SAR for both field strengths, 1.5T/64 MHz and 3T/128 MHz, respectively. The peak 1 gram averaged SAR reaches 216 W/kg and 103 W/kg for 64 MHz and 128 MHz, respectively. We also found that shortest stems, and the longest screws, typically induce higher peak SAR.
C1 [Zheng, Jianfeng; Li, Dawei; Chen, Ji] Univ Houston, Dept Elect & Comp Engn, Houston, TX 77004 USA.
[Kainz, Wolfgang] US FDA, Off Sci & Engn Labs, CDRH, Silver Spring, MD USA.
RP Zheng, JF (reprint author), Univ Houston, Dept Elect & Comp Engn, Houston, TX 77004 USA.
EM jzheng4@central.uh.edu; wolfgang.kainz@fda.hhs.gov
NR 13
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 2158-110X
BN 978-1-5090-1441-5
J9 IEEE INT SYMP ELEC
PY 2016
BP 116
EP 120
PG 5
WC Engineering, Electrical & Electronic; Physics, Applied
SC Engineering; Physics
GA BG1WI
UT WOS:000387117700044
ER
PT S
AU Guo, R
Zheng, JF
Chen, J
Kainz, W
AF Guo, Ran
Zheng, Jianfeng
Chen, Ji
Kainz, Wolfgang
GP IEEE
TI RF-Induced Heating Comparison Between in-vivo and in-phantom for 1.5T
MRI
SO 2016 IEEE INTERNATIONAL SYMPOSIUM ON ELECTROMAGNETIC COMPATIBILITY (EMC)
SE IEEE International Symposium on Electromagnetic Compatibility
LA English
DT Proceedings Paper
CT IEEE International Symposium on Electromagnetic Compatibility (EMC)
CY JUL 25-29, 2016
CL Ottawa, CANADA
SP IEEE Electromagnet Compatibil Soc
DE RF-induced heating; MRI; orthopedic plate
ID NUMERICAL-SIMULATION; IMPLANTS; DEVICES; COILS; SAR
AB The RF-induced heating is one of the main problems in diagnostic MRI. The standard way to assess the RF-induced heating is to perform experimental or computational phantom studies. Due to the inherent differences in geometry and electrical parameters between the phantom and the human body, the induced RF-induced heating assessed in the phantom is typically not be the same as in human body. In this study, we investigate the difference in RF-induced heating between in-vivo and in-phantom assessment for an orthopedic femur and a humerus plate systems at 1.5T (64 MHz). We found that for this particular device the RF-induced heating for the in-phantom simulations is always higher than for the in-vivo simulations. However, to accurately predict the maximum in-vivo heating it is necessary to perform computational modeling using anatomically correct computer models and accurate computer models of the implant.
C1 [Guo, Ran; Zheng, Jianfeng; Chen, Ji] Univ Houston, Dept Elect & Comp Engn, Houston, TX 77004 USA.
[Kainz, Wolfgang] US FDA, Off Sci & Engn Labs, CDRH, Silver Spring, MD USA.
RP Guo, R (reprint author), Univ Houston, Dept Elect & Comp Engn, Houston, TX 77004 USA.
EM rguo3@uh.edu; wolfgang.kainz@fda.hhs.gov
NR 18
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 2158-110X
BN 978-1-5090-1441-5
J9 IEEE INT SYMP ELEC
PY 2016
BP 121
EP 125
PG 5
WC Engineering, Electrical & Electronic; Physics, Applied
SC Engineering; Physics
GA BG1WI
UT WOS:000387117700045
ER
PT J
AU Planchart, A
Mattingly, CJ
Allen, D
Ceger, P
Casey, W
Hinton, D
Kanungo, J
Kullman, SW
Tal, T
Bondesson, M
Burgess, SM
Sullivan, C
Kim, C
Behl, M
Padilla, S
Reif, DM
Tanguay, RL
Hamm, J
AF Planchart, Antonio
Mattingly, Carolyn J.
Allen, David
Ceger, Patricia
Casey, Warren
Hinton, David
Kanungo, Jyotshna
Kullman, Seth W.
Tal, Tamara
Bondesson, Maria
Burgess, Shawn M.
Sullivan, Con
Kim, Carol
Behl, Mamta
Padilla, Stephanie
Reif, David M.
Tanguay, Robert L.
Hamm, Jon
TI Advancing Toxicology Research Using In Vivo High Throughput Toxicology
with Small Fish Models
SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
LA English
DT Article
DE aquatic models; 21st century toxicology; alternatives
ID ZEBRAFISH DANIO-RERIO; TRANSMEMBRANE CONDUCTANCE REGULATOR;
ENDOCRINE-DISRUPTING CHEMICALS; MATERNAL STILBESTROL THERAPY;
ARYL-HYDROCARBON RECEPTOR; INNATE IMMUNE-RESPONSE; ZINC-FINGER
NUCLEASES; CYPRINUS-CARPIO L.; ENVIRONMENTAL CHEMICALS; TRANSGENIC
ZEBRAFISH
AB Small freshwater fish models, especially zebrafish, offer advantages over traditional rodent models, including low maintenance and husbandry costs, high fecundity, genetic diversity, physiology similar to that of traditional biomedical models, and reduced animal welfare concerns. The Collaborative Workshop on Aquatic Models and 21st Century Toxicology was held at North Carolina State University on May 5-6, 2014, in Raleigh, North Carolina, USA. Participants discussed the ways in which small fish are being used as models to screen toxicants and understand mechanisms of toxicity. Workshop participants agreed that the lack of standardized protocols is an impediment to broader acceptance of these models, whereas development of standardized protocols, validation, and subsequent regulatory acceptance would facilitate greater usage. Given the advantages and increasing application of small fish models, there was widespread interest in follow-up workshops to review and discuss developments in their use. In this article, we summarize the recommendations formulated by workshop participants to enhance the utility of small fish species in toxicology studies, as well as many of the advances in the field of toxicology that resulted from using small fish species, including advances in developmental toxicology, cardiovascular toxicology, neurotoxicology, and immunotoxicology. We also review many emerging issues that will benefit from using small fish species, especially zebrafish, and new technologies that will enable using these organisms to yield results unprecedented in their information content to better understand how toxicants affect development and health.
C1 [Planchart, Antonio; Mattingly, Carolyn J.; Kullman, Seth W.; Reif, David M.] North Carolina State Univ, Dept Biol Sci, Campus Box 7633, Raleigh, NC 27695 USA.
[Planchart, Antonio; Mattingly, Carolyn J.; Kullman, Seth W.; Reif, David M.] North Carolina State Univ, Ctr Human Hlth & Environm, Raleigh, NC USA.
[Allen, David; Ceger, Patricia; Hamm, Jon] Integrated Lab Syst Inc, Res Triangle Pk, NC USA.
[Casey, Warren] NIEHS, Natl Toxicol Program, Interagency Ctr Evaluat Alternat Toxicol Methods, POB 12233, Res Triangle Pk, NC 27709 USA.
[Hinton, David] Duke Univ, Nicholas Sch Environm, Durham, NC 27708 USA.
[Kanungo, Jyotshna] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Tal, Tamara; Padilla, Stephanie] US EPA, Integrated Syst Toxicol Div, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA.
[Bondesson, Maria] Univ Houston, Dept Pharmacol & Pharmaceut Sci, Houston, TX USA.
[Burgess, Shawn M.] NHGRI, Bethesda, MD 20892 USA.
[Sullivan, Con; Kim, Carol] Univ Maine, Dept Mol & Biomed Sci, Orono, ME USA.
[Sullivan, Con; Kim, Carol] Univ Maine, Grad Sch Biomed Sci & Engn, Orono, ME USA.
[Behl, Mamta] NIEHS, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA.
[Tanguay, Robert L.] Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA.
RP Planchart, A (reprint author), North Carolina State Univ, Dept Biol Sci, Campus Box 7633, Raleigh, NC 27695 USA.
EM ajplanch@ncsu.edu
FU North Carolina State University Center for Human Health and the
Environment (NIH/NIEHS) [P30ES025128]
FX The authors would like to thank Ms. Catherine Sprankle of Integrated
Laboratory Systems, Inc., for editorial assistance. Financial support
for the workshop was provided by the North Carolina State University
Center for Human Health and the Environment (NIH/NIEHS P30ES025128).
NR 202
TC 1
Z9 1
U1 8
U2 8
PU SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH
PI HEILDEBERG
PA TIERGARTENSTRASSE 17, HEILDEBERG, 69121, GERMANY
SN 1868-596X
EI 1868-8551
J9 ALTEX-ALTERN ANIM EX
JI ALTEX-Altern. Anim. Exp.
PY 2016
VL 33
IS 4
BP 435
EP 452
DI 10.14573/altex.1601281
PG 18
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EB5RY
UT WOS:000387439200007
PM 27328013
ER
PT J
AU Luo, H
Mattes, W
Mendrick, DL
Hong, HX
AF Luo, Heng
Mattes, William
Mendrick, Donna L.
Hong, Huixiao
TI Molecular Docking for Identification of Potential Targets for Drug
Repurposing
SO CURRENT TOPICS IN MEDICINAL CHEMISTRY
LA English
DT Review
DE Docking; Drug; Target; Target identification; Drug repurposing
ID CHEMICAL-PROTEIN INTERACTOME; HIV-1 INTEGRASE INHIBITORS;
HUMAN-LEUKOCYTE ANTIGENS; STRUCTURE ELUCIDATION; DECISION FOREST;
EXPERT-SYSTEM; BINDING AFFINITIES; ALPHA-FETOPROTEIN; ESTROGENIC
ACTIVITY; CRYSTAL-STRUCTURES
AB Using existing drugs for new indications (drug repurposing) is an effective method not only to reduce drug development time and costs but also to develop treatments for new disease including those that are rare. In order to discover novel indications, potential target identification is a necessary step. One widely used method to identify potential targets is through molecule docking. It requires no prior information except structure inputs from both the drug and the target, and can identify potential targets for a given drug, or identify potential drugs for a specific target. Though molecular docking is popular for drug development and repurposing, challenges remain for the method. In order to improve the prediction accuracy, optimizing the target conformation, considering the solvents and adding cobinders to the system are possible solutions.
C1 [Luo, Heng; Mattes, William; Mendrick, Donna L.; Hong, Huixiao] US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
RP Hong, HX (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM huixiao.hong@fda.hhs.gov
FU Research Participation Program at the National Center for Toxicological
Research
FX The research was supported in part by an appointment to the Research
Participation Program at the National Center for Toxicological Research
(Heng Luo) administered by the Oak Ridge Institute for Science and
Education through an interagency agreement between the U.S. Department
of Energy and the U.S. Food and Drug Administration.
NR 95
TC 0
Z9 0
U1 3
U2 3
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1568-0266
EI 1873-5294
J9 CURR TOP MED CHEM
JI Curr. Top. Med. Chem.
PY 2016
VL 16
IS 30
BP 3636
EP 3645
DI 10.2174/1568026616666160530181149
PG 10
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA EB0ZI
UT WOS:000387075200008
PM 27334201
ER
PT J
AU Ye, H
Wei, J
Tang, KL
Feuers, R
Hong, HX
AF Ye, Hao
Wei, Jia
Tang, Kailin
Feuers, Ritchie
Hong, Huixiao
TI Drug Repositioning Through Network Pharmacology
SO CURRENT TOPICS IN MEDICINAL CHEMISTRY
LA English
DT Review
DE Drug repositioning; Network pharmacology; Pathway analysis
ID SACCHAROMYCES-CEREVISIAE GENOME; TARGET INTERACTION PREDICTION; DOCKING
APPROACH; WEB SERVER; PATHWAY ANALYSIS; DATABASE; DISEASE; BIOMARKERS;
DISCOVERY; BIOLOGY
AB Low drug productivity has been a significant problem of the pharmaceutical industry for several decades even though numerous novel technologies were introduced during this period. Currently pharmacologic dogma, "single drug, single target, single disease", is at the root of the lack of drug productivity. From a systems biology viewpoint, network pharmacology has been proposed to complement the established guiding pharmacologic approaches. The rationale for network pharmacology as a major component of drug discovery and development is that a disease can be caused by perturbation of the disease-causing network and a drug may be designed to interact with multiple targets for modulation of such a network from the disease status toward normal status. Therefore, network pharmacology has been applied to guide and assist in drug repositioning. Drugs exerting their therapeutic effects may directly target disease-associated proteins, but they may also modulate the pathways involved in the pathological process. In this review, we discuss the progresses and prospects in network pharmacology, focusing on drug off-targets discovery, disease-associated protein identification, and pathway analysis for elucidating relationships between drug targets and disease-associated proteins.
C1 [Ye, Hao; Hong, Huixiao] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Wei, Jia] AstraZeneca, R&D Informat, Shanghai, Peoples R China.
[Tang, Kailin] Tongji Univ, Sch Life Sci & Technol, Shanghai, Peoples R China.
[Feuers, Ritchie] US FDA, Off Res, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Hong, HX (reprint author), US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
EM huixiao.hong@fda.hhs.gov
FU Research Participation Program at the National Center for Toxicological
Research
FX This research was supported in part by an appointment to the Research
Participation Program at the National Center for Toxicological Research
(Hao Ye) administered by the Oak Ridge Institute for Science and
Education through an interagency agreement between the U.S. Department
of Energy and the U.S. Food and Drug Administration. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the Food and Drugs Administration.
NR 96
TC 0
Z9 0
U1 8
U2 8
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1568-0266
EI 1873-5294
J9 CURR TOP MED CHEM
JI Curr. Top. Med. Chem.
PY 2016
VL 16
IS 30
BP 3646
EP 3656
DI 10.2174/1568026616666160530181328
PG 11
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA EB0ZI
UT WOS:000387075200009
PM 27334200
ER
PT J
AU Lefebvre, RC
McCormack, L
Taylor, O
Bann, C
Rausch, P
AF Lefebvre, R. Craig
McCormack, Lauren
Taylor, Olivia
Bann, Carla
Rausch, Paula
TI A quantitative approach to segmentation for prescription drug safety
programs
SO JOURNAL OF SOCIAL MARKETING
LA English
DT Article
DE Social marketing; Consumer attitudes; Audience research; Segmentation;
Pharmacovigilance; Drug safety
ID HEALTH LITERACY; INFORMATION-SEEKING; PUBLIC-HEALTH; RISK;
COMMUNICATION; PHARMACEUTICALS; INSTRUMENT; STRATEGIES; CONSUMERS;
OUTCOMES
AB Purpose - The aim of this paper is to enhance the effectiveness of pharmacovigilance programs that provide information about medical products to benefit consumers, aid health care professional's decision-making and improve community health. This research sought to determine whether distinct segments of consumers can be identified for prescription drug safety social marketing and communication activities and if these segments would respond differently to information about prescription drug products.
Design/methodology/approach - Theories of risk information-seeking behavior were used to develop questions for respondents in an online survey panel. Latent class analyses identified clusters that were similar in their ability to accurately interpret risks and benefits, preferred sources of health information, medication use and other related factors. Multinomial logistic regression models identified demographic and psychographic differences across the segments. Logistic and linear regression models were then used to compare each segment's responses to a specific drug safety information product.
Findings - The 1,244 respondents were clustered into four segments: not engaged (12 per cent), low-involvement users (29 per cent), careful users (50 per cent) and social information seekers (9 per cent). These segments were distinguished by perceived seeking control, self-appraisal of skill, information insufficiency, self-efficacy, information competency and health literacy. Sources of health information and health-seeking behaviors were also different across the four segments. Significant differences were found among the segments in their comprehension and perceived utility of the content and their intentions to take relevant actions.
Practical implications - From an array of potential behavioral influences, adults can be segmented by risk information-seeking constructs and related behaviors. These segments respond differently to drug safety information. Use of the personas developed in this work can help pharmacovigilance programs around the world develop more relevant and tailored social marketing products, services and content.
Originality/value - A social marketing approach using empirically tested theoretical constructs can be useful for drug safety or pharmacovigilance programs. The results were used to create personas that quickly convey relevant information to drug safety program managers and staff.
C1 [Lefebvre, R. Craig; McCormack, Lauren; Taylor, Olivia] RTI Int, Ctr Commun Sci, Res Triangle Pk, NC 27709 USA.
[Bann, Carla] RTI Int, Social Stat & Environm Sci Dept, Res Triangle Pk, NC USA.
[Rausch, Paula] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Lefebvre, RC (reprint author), RTI Int, Ctr Commun Sci, Res Triangle Pk, NC 27709 USA.
EM clefebvre@rti.org
NR 42
TC 0
Z9 0
U1 2
U2 2
PU EMERALD GROUP PUBLISHING LTD
PI BINGLEY
PA HOWARD HOUSE, WAGON LANE, BINGLEY BD16 1WA, W YORKSHIRE, ENGLAND
SN 2042-6763
EI 2042-6771
J9 J SOC MARKET
JI J. Soc. Market.
PY 2016
VL 6
IS 4
BP 335
EP 360
DI 10.1108/JSOCM-06-2014-0037
PG 26
WC Business
SC Business & Economics
GA EB3HI
UT WOS:000387254300002
ER
PT J
AU Tcheuko, L
Gallas, B
Samuelson, F
AF Tcheuko, Lucas
Gallas, Brandon
Samuelson, Frank
TI Using ANOVA/random-effects variance estimates to compute a two-sample
U-statistic of order (1,1) estimate of variance
SO JOURNAL OF STATISTICAL THEORY AND PRACTICE
LA English
DT Article
DE AUC; ROC; variance components; rank statistic; ANOVA
ID NONPARAMETRIC APPROACH
AB The classical empirical, area under the receiver operating characteristic (ROC) curve (AUC) is a two-sample U-statistic of order (1,1). Its variance can be written out as a sum of three tractable covariances. It is then possible to consider each of these covariances as U-statistics themselves and follow the U-statistics formalism to derive their unbiased estimates. Over the years, alternative methods have been proposed to estimate the variance of AUC. For example, Delong et al. have proposed a straightforward estimate that has attractive asymptotic properties. At small sample sizes, however, the DeLong method will be biased. In the early stage of investigation, researchers don't always have enough data; therefore, those asymptotic variance estimates such as DeLong's can be unreliable. In this article we propose a two-way random effects analysis of variance (ANOVA) method to compute an unbiased variance estimate of a two-sample U-statistic of order (1,1) in general, and of the AUC in particular. We prove that this variance estimate is equal to the fully U-statistic result. In the particular case of the AUC variance estimate we compare our result to DeLong's AUC variance estimate. We extend the result to obtain an unbiased estimate of variance for a linear combination of possibly correlated AUCs. A natural consequence of this extension is the estimate of variance of the difference of the areas under two correlated ROC curves. This difference is of interest in many diagnostic studies, namely, the comparison of two different modalities used to diagnose the same disease.
C1 [Tcheuko, Lucas; Gallas, Brandon; Samuelson, Frank] US FDA, Silver Spring, MD USA.
RP Tcheuko, L (reprint author), US FDA, CDRH OSB DBS, 10903 New Hampshire Ave, Silver Spring, MD 20943 USA.
EM lucast@math.umd.edu
NR 13
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS AS
PI OSLO
PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY
SN 1559-8608
EI 1559-8616
J9 J STAT THEORY PRACT
JI J. Stat. Theory Pract.
PY 2016
VL 10
IS 1
BP 87
EP 99
DI 10.1080/15598608.2015.1077759
PG 13
WC Statistics & Probability
SC Mathematics
GA EA7GG
UT WOS:000386797800007
ER
PT J
AU Huang, X
Wang, QY
Zheng, J
Chen, J
Ghosn, M
Shah, DJ
Kainz, W
AF Huang, Xin
Wang, Qingyan
Zheng, Jason
Chen, Ji
Ghosn, Mohamad
Shah, Dipan J.
Kainz, Wolfgang
GP IEEE
TI Using Transfer Function Approach To Develop MRI Visible and Low RF
Heating Sleeve for Cardiac Applicaion
SO 2016 IEEE/ACES INTERNATIONAL CONFERENCE ON WIRELESS INFORMATION
TECHNOLOGY AND SYSTEMS (ICWITS) AND APPLIED COMPUTATIONAL
ELECTROMAGNETICS (ACES)
LA English
DT Proceedings Paper
CT IEEE/ACES International Conference on Wireless Information Technology
(ICWITS) and System and Applied Computational Electromagnetics (ACES)
CY MAR 13-17, 2016
CL Honolulu, HI
SP IEEE Antennas & Propagat Soc, Appl Computat Electromagnet Soc, IEEE
DE MRI RF Heating; MRI Visible Catheter
ID IMPLANTED PACEMAKERS; APPARATUS
AB A method is developed to evaluate the design of MRI visible and low heating catheter coating layer for cardiac and neuromodulation applications. The procedure consists of both experimental characterization of the coating layer as well as detailed electromagnetic simulation of human subject models during MRI procedure. Practical examples are used to demonstrate the effectiveness of this procedure.
C1 [Huang, Xin; Wang, Qingyan; Zheng, Jason; Chen, Ji] Univ Houston, Dept Elect & Comp Engn, Houston, TX 77204 USA.
[Ghosn, Mohamad; Shah, Dipan J.] Houston Methodist DeBakey Heart & Vasc Ctr, 6550 Fannin St,Smith Tower,Suite 677, Houston, TX 77030 USA.
[Kainz, Wolfgang] US FDA, Ctr Device & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
RP Huang, X (reprint author), Univ Houston, Dept Elect & Comp Engn, Houston, TX 77204 USA.
NR 2
TC 0
Z9 0
U1 1
U2 1
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
BN 978-1-5090-1259-6
PY 2016
PG 2
WC Computer Science, Theory & Methods; Engineering, Electrical &
Electronic; Telecommunications
SC Computer Science; Engineering; Telecommunications
GA BG0WM
UT WOS:000386537100143
ER
PT J
AU Wang, W
Zhang, B
AF Wang, Wei
Zhang, Bo
TI Assessing natural direct and indirect effects for a continuous exposure
and a dichotomous outcome
SO JOURNAL OF STATISTICAL THEORY AND PRACTICE
LA English
DT Article
DE Continuous exposure; mediation formula; natural direct effect; natural
indirect effect; potential outcomes framework; sensitivity analysis
ID MEDIATION ANALYSIS; MODELS; DISEASE; REGRESSION; INFERENCE; OBESITY
AB Recent advances in the literature on mediation have extended from a traditional linear structural equation modeling approach to causal mediation analysis using potential outcomes framework. Pearl proposed a mediation formula to calculate expected potential outcomes used in the natural direct and indirect effects definition under the key sequential ignorability assumptions. Current methods mainly focused on binary exposure variables, and in this article, this approach is further extended to settings in which continuous exposures may be of interest. Focusing on a dichotomous outcome, we give precise definitions of the natural direct and indirect effects on both the risk difference and odds ratio scales utilizing the empirical joint distribution of the exposure and baseline covariates from the whole sample analysis population. A mediation-formula-based approach is proposed to estimate the corresponding causal quantities. Simulation study is conducted to assess the statistical properties of the proposed method, and we illustrate our approach by applying it to the Jackson Heart Study to estimate the mediation effects of diabetes on the relation between obesity and chronic kidney disease. Sensitivity analysis is performed to assess the impact of violation of no unmeasured mediator-outcome confounder assumption.
C1 [Wang, Wei] Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, New Guyton Res Bldg G562,2500 North State St, Jackson, MS 39216 USA.
[Zhang, Bo] US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Wang, W (reprint author), Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, New Guyton Res Bldg G562,2500 North State St, Jackson, MS 39216 USA.
EM wwang@umc.edu
NR 27
TC 0
Z9 0
U1 2
U2 2
PU TAYLOR & FRANCIS AS
PI OSLO
PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY
SN 1559-8608
EI 1559-8616
J9 J STAT THEORY PRACT
JI J. Stat. Theory Pract.
PY 2016
VL 10
IS 3
BP 574
EP 587
DI 10.1080/15598608.2016.1203843
PG 14
WC Statistics & Probability
SC Mathematics
GA EA7GT
UT WOS:000386799300007
PM 28255292
ER
PT S
AU Bakic, PR
Myers, KJ
Glick, SJ
Maidment, ADA
AF Bakic, Predrag R.
Myers, Kyle J.
Glick, Stephen J.
Maidment, Andrew D. A.
CA AAPM Task Grp 234
BE Tingberg, A
Lang, K
Timberg, P
TI Virtual Tools for the Evaluation of Breast Imaging: State-of-the Science
and Future Directions
SO BREAST IMAGING, IWDM 2016
SE Lecture Notes in Computer Science
LA English
DT Proceedings Paper
CT 13th International Workshop on Breast Imaging (IWDM)
CY JUN 19-22, 2016
CL Malmo, SWEDEN
DE Mammography; Digital breast tomosynthesis; Breast imaging simulation;
Anthropomorphic phantoms; Virtual clinical trials; Model observers
AB The beginning of this century saw the development of simulation methods for the evaluation of breast imaging, motivated by the limitations of conventional clinical trials. This has led to the formation of AAPM Task Group on Virtual Tools for the Validation of 3D/4D X-ray Breast Imaging Systems (TG234), gathering researchers from academia, industry, and government, interested in the development, testing, and adoption of these tools. TG234 is currently finalizing its report. The report has been designed as an experiential guide through the steps of simulating breast anatomy, image acquisition, image interpretation, and analysis. TG234 activities include disseminating the idea of virtual clinical trials through numerous focused conference sessions and AAPM annual meeting symposia. This paper reflects our desire to initiate wider discussion about the future directions in the development of virtual tools for the design and evaluation of novel breast imaging systems.
C1 [Bakic, Predrag R.; Maidment, Andrew D. A.] Univ Penn, Dept Radiol, Philadelphia, PA USA.
[Myers, Kyle J.; Glick, Stephen J.; AAPM Task Grp 234] US FDA, Silver Spring, MD USA.
RP Bakic, PR (reprint author), Univ Penn, Dept Radiol, Philadelphia, PA USA.
EM Predrag.Bakic@uphs.upenn.edu
NR 9
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 0302-9743
BN 978-3-319-41546-8; 978-3-319-41545-1
J9 LECT NOTES COMPUT SC
PY 2016
VL 9699
BP 518
EP 524
DI 10.1007/978-3-319-41546-8_65
PG 7
WC Computer Science, Software Engineering; Computer Science, Theory &
Methods; Imaging Science & Photographic Technology; Radiology, Nuclear
Medicine & Medical Imaging
SC Computer Science; Imaging Science & Photographic Technology; Radiology,
Nuclear Medicine & Medical Imaging
GA BG0LB
UT WOS:000386324200065
ER
PT S
AU Ikejimba, L
Graff, C
Glick, S
AF Ikejimba, Lynda
Graff, Christian
Glick, Stephen
BE Tingberg, A
Lang, K
Timberg, P
TI Rapid Generation of Structured Physical Phantoms for Mammography and
Digital Breast Tomosynthesis
SO BREAST IMAGING, IWDM 2016
SE Lecture Notes in Computer Science
LA English
DT Proceedings Paper
CT 13th International Workshop on Breast Imaging (IWDM)
CY JUN 19-22, 2016
CL Malmo, SWEDEN
DE Breast phantom; Anthropomorphic; Iodine; Linear attenuation
AB Nonuniform phantoms are needed in order to fully characterize the impact of anatomical structures on system performance in mammography and digital breast tomosynthesis (DBT). In this work, a new type of textured physical phantom is presented, compatible for use in both 2D and 3D applications. The breast phantom was first modeled analytically, and then fabricated using inkjet printing onto parchment paper and slide transparencies. A radiographic ink solution was synthesized with 350 mg/mL iohexol and pigmented ink. The effective linear attenuation coefficient (mu(eff)) of the parchment paper alone (0.078 +/- 0.003 mm(-1)) was found to be very close to that of a 70 % adipose, 30 % fibroglandular tissue mixture (0.078 +/- 0.004 mm(-1)). The mu(eff) of the parchment paper with iodine (0.010 +/- 0.005 mm(-1)) was close to that of 100 % fibroglandular tissue (0.11 +/- 0.004 mm(-1)). This new parchment and iodine phantom has strong potential for use in imaging studies.
C1 [Ikejimba, Lynda; Graff, Christian; Glick, Stephen] US FDA, Div Imaging Diagnost & Software Reliabil, OSEL, CDRH, Silver Spring, MD 20993 USA.
RP Ikejimba, L (reprint author), US FDA, Div Imaging Diagnost & Software Reliabil, OSEL, CDRH, Silver Spring, MD 20993 USA.
EM Lynda.Ikejimba@fda.hhs.gov; Christian.Graff@fda.hhs.gov;
Stephen.Glick@fda.hhs.gov
NR 7
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 0302-9743
BN 978-3-319-41546-8; 978-3-319-41545-1
J9 LECT NOTES COMPUT SC
PY 2016
VL 9699
BP 654
EP 659
DI 10.1007/978-3-319-41546-8_81
PG 6
WC Computer Science, Software Engineering; Computer Science, Theory &
Methods; Imaging Science & Photographic Technology; Radiology, Nuclear
Medicine & Medical Imaging
SC Computer Science; Imaging Science & Photographic Technology; Radiology,
Nuclear Medicine & Medical Imaging
GA BG0LB
UT WOS:000386324200081
ER
PT J
AU Zhu, H
Bouhifd, M
Donley, E
Egnash, L
Kleinstreuer, N
Kroese, ED
Liu, ZC
Luechtefeld, T
Palmer, J
Pamies, D
Shen, J
Strauss, V
Wu, SD
Hartung, T
AF Zhu, Hao
Bouhifd, Mounir
Donley, Elizabeth
Egnash, Laura
Kleinstreuer, Nicole
Kroese, E. Dinant
Liu, Zhichao
Luechtefeld, Thomas
Palmer, Jessica
Pamies, David
Shen, Jie
Strauss, Volker
Wu, Shengde
Hartung, Thomas
TI Supporting Read-Across Using Biological Data
SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
LA English
DT Article
DE read-across; biological similarity; safety assessment; big data
ID COMPARATIVE TOXICOGENOMICS DATABASE; COMPUTATIONAL TOXICOLOGY RESOURCE;
DETECTING REPRODUCTIVE TOXICANTS; ADVERSE OUTCOME PATHWAY; VITRO TEST
BATTERY; IN-VITRO; RISK-ASSESSMENT; ENVIRONMENTAL CHEMICALS;
DEVELOPMENTAL TOXICITY; SCREENING ASSAYS
AB Read-across, i.e., filling toxicological data gaps by relating to similar chemicals for which test data are available, is usually done based on chemical similarity. Besides structure and physico-chemical properties, biological similarity based on biological data adds extra strength to this process. In the simplest case, chemically similar substances also show similar test results in relevant in vitro assays. This is a well-established method for the read-across of, e.g., genotoxicity assays. Larger datasets of biological and toxicological properties of hundreds and thousands of substances are becoming available, enabling big data approaches in read-across studies. In the context of developing Good Read-Across Practice guidance, a number of case studies using various big data sources were evaluated to assess the contribution of biological data to enriching read-across. An example is given for the US EPA's ToxCast dataset which allows read-across for high quality uterotrophic assays for estrogenic endocrine disruption. Similarly, an example is given for REACH registration data that enhances read-across for acute toxicity studies. A different approach is taken using omics data to establish biological similarity: Examples are given for in vitro stem cell models and short-term in vivo repeated dose studies in rats used to support read-across and category formation. These preliminary biological data-driven read-across studies show the way towards the generation of new read-across approaches that can inform chemical safety assessment.
C1 [Zhu, Hao] Rutgers State Univ, Dept Chem, Camden, NJ USA.
[Zhu, Hao] Rutgers State Univ, Ctr Computat & Integrat Biol, Camden, NJ USA.
[Bouhifd, Mounir; Luechtefeld, Thomas; Pamies, David; Hartung, Thomas] Johns Hopkins Bloomberg Sch Publ Hlth, CAAT, Baltimore, MD USA.
[Donley, Elizabeth; Egnash, Laura; Palmer, Jessica] Stemina Biomarker Discovery Inc, Madison, WI USA.
[Kleinstreuer, Nicole] NIEHS, Natl Toxicol Program, Interagency Ctr Evaluat Alternat Toxicol Methods, POB 12233, Res Triangle Pk, NC 27709 USA.
[Kroese, E. Dinant] TNO, Risk Anal Prod Dev, Zeist, Netherlands.
[Liu, Zhichao] US FDA, NCTR, Little Rock, AR USA.
[Shen, Jie] Res Inst Fragrance Mat Inc, Woodcliff Lake, NJ USA.
[Strauss, Volker] BASF Aktiengesellsch Expt Toxicol & Ecol, Ludwigshafen, Germany.
[Wu, Shengde] Procter & Gamble, Cincinnati, OH USA.
[Hartung, Thomas] Univ Konstanz, CAAT Europe, Constance, Germany.
RP Hartung, T (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Alternat Anim Testing, 615 North Wolfe St, Baltimore, MD 21205 USA.
EM thartun1@jhu.edu
OI Kleinstreuer, Nicole/0000-0002-7914-3682
FU NIEHS training grant [T32 ES007141]; EU Horizon 2020 project EUToxRisk
FX T.L. was supported by NIEHS training grant (T32 ES007141). Support from
the EU Horizon 2020 project EUToxRisk is gratefully appreciated.
NR 110
TC 7
Z9 7
U1 8
U2 9
PU SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH
PI HEILDEBERG
PA TIERGARTENSTRASSE 17, HEILDEBERG, 69121, GERMANY
SN 1868-596X
EI 1868-8551
J9 ALTEX-ALTERN ANIM EX
JI ALTEX-Altern. Anim. Exp.
PY 2016
VL 33
IS 2
BP 167
EP 182
DI 10.14573/altex.1601252
PG 16
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DZ0FI
UT WOS:000385512500008
PM 26863516
ER
PT J
AU Marx, U
Andersson, TB
Bahinski, A
Beilmann, M
Beken, S
Cassee, FR
Cirit, M
Daneshian, M
Fitzpatrick, S
Frey, O
Gaertner, C
Giese, C
Griffith, L
Hartung, T
Heringa, MB
Hoeng, J
de Jong, WH
Kojima, H
Kuehnl, J
Leist, M
Luch, A
Maschmeyer, I
Sakharov, D
Sips, AJAM
Steger-Hartmann, T
Tagle, DA
Tonevitsky, A
Tralau, T
Tsyb, S
van de Stolpe, A
Vandebriel, R
Vulto, P
Wang, JF
Wiest, J
Rodenburg, M
Roth, A
AF Marx, Uwe
Andersson, Tommy B.
Bahinski, Anthony
Beilmann, Mario
Beken, Sonja
Cassee, Flemming R.
Cirit, Murat
Daneshian, Mardas
Fitzpatrick, Susan
Frey, Olivier
Gaertner, Claudia
Giese, Christoph
Griffith, Linda
Hartung, Thomas
Heringa, Minne B.
Hoeng, Julia
de Jong, Wim H.
Kojima, Hajime
Kuehnl, Jochen
Leist, Marcel
Luch, Andreas
Maschmeyer, Ilka
Sakharov, Dmitry
Sips, Adrienne J. A. M.
Steger-Hartmann, Thomas
Tagle, Danilo A.
Tonevitsky, Alexander
Tralau, Tewes
Tsyb, Sergej
van de Stolpe, Anja
Vandebriel, Rob
Vulto, Paul
Wang, Jufeng
Wiest, Joachim
Rodenburg, Marleen
Roth, Adrian
TI Biology-Inspired Microphysiological System Approaches to Solve the
Prediction Dilemma of Substance Testing
SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
LA English
DT Editorial Material
DE microphysiological systems; organ-on-a-chip; in vitro models; predictive
toxicology; drug testing
ID ON-A-CHIP; PLURIPOTENT STEM-CELLS; SKIN SENSITIZATION POTENCY;
NEURAL-NETWORK ANALYSIS; LYMPH-NODE ASSAY; MULTI-ORGAN-CHIP; IN-VITRO
MODELS; SCREENING CONTACT ALLERGENS; OF-THE-ART; MICROFLUIDIC DEVICE
AB The recent advent of microphysiological systems-microfluidic biomimetic devices that aspire to emulate the biology of human tissues, organs and circulation in vitro-promises to enable a global paradigm shift in drug development. An extraordinary US government initiative and various dedicated research programs in Europe and Asia recently have led to the first cutting-edge achievements of human single-organ and multi-organ engineering based on microphysiological systems. The expectation is that test systems established on this basis will model various disease stages and predict toxicity, immunogenicity, ADME profiles and treatment efficacy prior to clinical testing. Consequently, this technology could significantly affect the way drug substances are developed in the future. Furthermore, microphysiological system-based assays may revolutionize our current global programs of prioritization of hazard characterization for any new substances to be used, for example, in agriculture, food, ecosystems or cosmetics, thus replacing the use of laboratory animal models. Here, thirty-six experts from academia, industry and regulatory bodies present the results of an intensive workshop (held in June 2015, Berlin, Germany). They review the status quo of microphysiological systems available today against industry needs, and assess the broad variety of approaches with fit-for-purpose potential in the drug development cycle. Feasible technical solutions to reach the next levels of human biology in vitro are proposed. Furthermore, key organ-on-a-chip case studies as well as various national and international programs are highlighted. Finally, a roadmap into the future towards more predictive and regulatory-accepted substance testing on a global scale is outlined.
C1 [Marx, Uwe; Maschmeyer, Ilka] TissUse GmbH, Berlin, Germany.
[Andersson, Tommy B.] AstraZeneca, Cardiovasc & Metab Dis Innovat Med & Early Dev Bi, Molndal, Sweden.
[Andersson, Tommy B.] Karolinska Inst, Dept Physiol & Pharmacol, Pharmacogenet Sect, Stockholm, Sweden.
[Bahinski, Anthony] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.
[Beilmann, Mario] Boehringer Ingelheim Pharma GmbH & Co KG, Nonclin Drug Safety, Biberach, Germany.
[Beken, Sonja] Fed Agcy Med & Hlth Prod, Brussels, Belgium.
[Cassee, Flemming R.; Heringa, Minne B.; de Jong, Wim H.; Sips, Adrienne J. A. M.; Vandebriel, Rob; Rodenburg, Marleen] Natl Inst Publ Hlth & Environm, Bilthoven, Netherlands.
[Cassee, Flemming R.] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
[Cirit, Murat; Griffith, Linda] MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Daneshian, Mardas; Hartung, Thomas; Leist, Marcel] Univ Konstanz, Ctr Alternat Anim Testing Europe, Constance, Germany.
[Fitzpatrick, Susan] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
[Frey, Olivier] Swiss Fed Inst Technol, Bio Engn Lab, Dept Biosyst Sci & Engn, Basel, Switzerland.
[Gaertner, Claudia] Microfluid ChipShop GmbH, Jena, Germany.
[Giese, Christoph] ProBioGen AG, Berlin, Germany.
[Hartung, Thomas] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Ctr Alternat Anim Testing, Baltimore, MD USA.
[Hoeng, Julia] Philip Morris Int R&D, Neuchatel, Switzerland.
[Kojima, Hajime] Japanese Ctr Validat Anim Methods, Tokyo, Japan.
[Kuehnl, Jochen] Beiersdorf, Hamburg, Germany.
[Luch, Andreas; Tralau, Tewes] German Fed Inst Risk Assessment, Dept Chem & Prod Safety, Berlin, Germany.
[Sakharov, Dmitry] Sci Res Ctr Bioclinicum, Moscow, Russia.
[Steger-Hartmann, Thomas] Bayer, Invest Toxicol, Berlin, Germany.
[Tagle, Danilo A.] Natl Ctr Adv Translat Sci, NIH, Bethesda, MD USA.
[Tonevitsky, Alexander] Natl Ctr Med Radiol Res, Moscow, Russia.
[Tsyb, Sergej] Russian Minist Prod & Trade, Moscow, Russia.
[van de Stolpe, Anja] Inst Human Organ & Dis Model Technol, Leiden, Netherlands.
[Vulto, Paul] MIMETAS BV, Leiden, Netherlands.
[Wang, Jufeng] Chinese Natl Ctr Safety Evaluat Drugs, Beijing, Peoples R China.
[Wiest, Joachim] Cellasys GmbH, Kronburg, Germany.
[Roth, Adrian] F Hoffmann La Roche Ltd, Roche Innovat Ctr Basel, Basel, Switzerland.
RP Marx, U (reprint author), TissUse GmbH, Berlin, Germany.
EM Uwe.marx@tissuse.com
RI Frey, Olivier/G-7065-2011; Leist, Marcel/D-2133-2010;
OI Frey, Olivier/0000-0002-4259-3751; Leist, Marcel/0000-0002-3778-8693;
Wiest, Joachim/0000-0003-4372-9523; Tonevitsky,
Alexander/0000-0002-7079-7145
NR 374
TC 6
Z9 6
U1 15
U2 15
PU SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH
PI HEILDEBERG
PA TIERGARTENSTRASSE 17, HEILDEBERG, 69121, GERMANY
SN 1868-596X
EI 1868-8551
J9 ALTEX-ALTERN ANIM EX
JI ALTEX-Altern. Anim. Exp.
PY 2016
VL 33
IS 3
BP 272
EP 321
DI 10.14573/altex.1603161
PG 50
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DZ0FW
UT WOS:000385513900008
PM 27180100
ER
PT J
AU Biglan, KM
Shoulson, I
Kieburtz, K
Oakes, D
Kayson, E
Shinaman, MA
Zhao, HW
Romer, M
Young, A
Hersch, S
Penney, J
Marder, K
Paulsen, J
Quaid, K
Siemers, E
Tanner, C
Mallonee, W
Suter, G
Dubinsky, R
Gray, C
Nance, M
Bundlie, S
Radtke, D
Kostyk, S
Baic, C
Caress, J
Walker, F
Hunt, V
O'Neill, C
Chouinard, S
Factor, S
Greenamyre, T
Wood-Siverio, C
Corey-Bloom, J
Song, D
Peavy, G
Moskowitz, C
Wesson, M
Samii, A
Bird, T
Lipe, H
Blindauer, K
Marshall, F
Zimmerman, C
Goldstein, J
Rosas, D
Novak, P
Caviness, J
Adler, C
Duffy, A
Wheelock, V
Tempkin, T
Richman, D
Seeberger, L
Albin, R
Chou, KL
Racette, B
Perlmutter, JS
Perlman, S
Bordelon, Y
Martin, W
Wieler, M
Leavitt, B
Raymond, L
Decolongon, J
Clarke, L
Jankovic, J
Hunter, C
Hauser, RA
Sanchez-Ramos, J
Furtado, S
Suchowersky, O
Klimek, ML
Guttman, M
Sethna, R
Feigin, A
Cox, M
Shannon, B
Percy, A
Dure, L
Harrison, M
Johnson, W
Higgins, D
Molho, E
Nickerson, C
Evans, S
Hobson, D
Singer, C
Galvez-Jimenez, N
Shannon, K
Comella, C
Ross, C
Saint-Hilaire, MH
Testa, C
Rosenblatt, A
Hogarth, P
Weiner, W
Como, P
Kumar, R
Cotto, C
Stout, J
Brocht, A
Watts, A
Eberly, S
Weaver, C
Foroud, T
Gusella, J
MacDonald, M
Myers, R
Fahn, S
Shults, C
AF Biglan, Kevin Michael
Shoulson, Ira
Kieburtz, Karl
Oakes, David
Kayson, Elise
Shinaman, M. Aileen
Zhao, Hongwei
Romer, Megan
Young, Anne
Hersch, Steven
Penney, Jack
Marder, Karen
Paulsen, Jane
Quaid, Kimberly
Siemers, Eric
Tanner, Caroline
Mallonee, William
Suter, Greg
Dubinsky, Richard
Gray, Carolyn
Nance, Martha
Bundlie, Scott
Radtke, Dawn
Kostyk, Sandra
Baic, Corrine
Caress, James
Walker, Francis
Hunt, Victoria
O'Neill, Christine
Chouinard, Sylvain
Factor, Stewart
Greenamyre, Timothy
Wood-Siverio, Cathy
Corey-Bloom, Jody
Song, David
Peavy, Guerry
Moskowitz, Carol
Wesson, Melissa
Samii, Ali
Bird, Thomas
Lipe, Hillary
Blindauer, Karen
Marshall, Frederick
Zimmerman, Carol
Goldstein, Jody
Rosas, Diana
Novak, Peter
Caviness, John
Adler, Charles
Duffy, Amy
Wheelock, Vicki
Tempkin, Teresa
Richman, David
Seeberger, Lauren
Albin, Roger
Chou, Kelvin L.
Racette, Brad
Perlmutter, Joel S.
Perlman, Susan
Bordelon, Yvette
Martin, Wayne
Wieler, Marguerite
Leavitt, Blair
Raymond, Lynn
Decolongon, Joji
Clarke, Lorne
Jankovic, Joseph
Hunter, Christine
Hauser, Robert A.
Sanchez-Ramos, Juan
Furtado, Sarah
Suchowersky, Oksana
Klimek, Mary Lou
Guttman, Mark
Sethna, Rustom
Feigin, Andrew
Cox, Marie
Shannon, Barbara
Percy, Alan
Dure, Leon
Harrison, Madaline
Johnson, William
Higgins, Donald
Molho, Eric
Nickerson, Constance
Evans, Sharon
Hobson, Douglas
Singer, Carlos
Galvez-Jimenez, Nestor
Shannon, Kathleen
Comella, Cynthia
Ross, Christopher
Saint-Hilaire, Marie H.
Testa, Claudia
Rosenblatt, Adam
Hogarth, Penelope
Weiner, William
Como, Peter
Kumar, Rajeev
Cotto, Candace
Stout, Julie
Brocht, Alicia
Watts, Arthur
Eberly, Shirley
Weaver, Christine
Foroud, Tatiana
Gusella, James
MacDonald, Marcy
Myers, Richard
Fahn, Stanley
Shults, Clifford
CA Huntington Study Grp PHAROS Invest
TI Clinical-Genetic Associations in the Prospective Huntington at Risk
Observational Study (PHAROS) Implications for Clinical Trials
SO JAMA NEUROLOGY
LA English
DT Article
ID CAG REPEAT LENGTH; PREDICT-HD; COGNITIVE DECLINE; FLUENCY DEFICITS;
TRACK-HD; DISEASE; PREMANIFEST; PROGRESSION; DIAGNOSIS; CARRIERS
AB IMPORTANCE Identifying measures that are associated with the cytosine-adenine-guanine (CAG) expansion in individuals before diagnosis of Huntington disease (HD) has implications for designing clinical trials.
OBJECTIVE To identify the earliest features associated with the motor diagnosis of HD in the Prospective Huntington at Risk Observational Study (PHAROS).
DESIGN, SETTING, AND PARTICIPANTS A prospective, multicenter, longitudinal cohort study was conducted at 43 US and Canadian Huntington Study Group research sites from July 9, 1999, through December 17, 2009. Participants included 983 unaffected adults at risk for HD who had chosen to remain unaware of their mutation status. Baseline comparability between CAG expansion (>= 37 repeats) and nonexpansion (<37 repeats) groups was assessed. All participants and investigators were blinded to individual CAG analysis. A repeated-measures analysis adjusting for age and sex was used to assess the divergence of the linear trend between the expanded and nonexpanded groups. Data were analyzed from April 27, 2010, to September 3, 2013.
EXPOSURE Huntington disease mutation status in individuals with CAG expansion vs without CAG expansion.
MAIN OUTCOMES AND MEASURES Unified Huntington's Disease Rating Scale motor (score range, 0-124; higher scores indicate greater impairment), cognitive (symbol digits modality is the total number of correct responses in 90 seconds; lower scores indicate greater impairment), behavioral (score range, 0-176; higher scores indicate greater behavioral symptoms), and functional (Total Functional Capacity score range, 0-13; lower scores indicate reduced functional ability) domains were assessed at baseline and every 9 months up to a maximum of 10 years.
RESULTS Among the 983 research participants at risk for HD in the longitudinal cohort, 345 (35.1%) carried the CAG expansion and 638 (64.9%) did not. The mean (SD) duration of follow-up was 5.8 (3.0) years. At baseline, participants with expansions had more impaired motor (3.0 [4.2] vs 1.9 [2.8]; P < .001), cognitive (P < .05 for all measures except Verbal Fluency, P = .52), and behavioral domain scores (9.4 [11.4] vs 6.5 [8.5]; P < .001) but not significantly different measures of functional capacity (12.9 [0.3] vs 13.0 [0.2]; P = .23). With findings reported as mean slope (95% CI), in the longitudinal analyses, participants with CAG expansions showed significant worsening in motor (0.84 [0.73 to 0.95] vs 0.03 [-0.05 to 0.11]), cognitive (-0.54 [-0.67 to -0.40] vs 0.22 [0.12 to 0.32]), and functional (-0.08 [-0.09 to -0.06] vs -0.01 [-0.02 to 0]) measures compared with those without expansion (P < .001 for all); behavioral domain scores did not diverge significantly between groups.
CONCLUSIONS AND RELEVANCE Using these prospectively accrued clinical data, relatively large treatment effects would be required to mount a randomized, placebo-controlled clinical trial involving premanifest HD individuals who carry the CAG expansion.
C1 [Biglan, Kevin Michael; Kieburtz, Karl; Kayson, Elise; Shinaman, M. Aileen; Marshall, Frederick; Zimmerman, Carol; Goldstein, Jody; Brocht, Alicia; Watts, Arthur; Weaver, Christine] Univ Rochester, Dept Neurol, Rochester, NY 14642 USA.
[Shoulson, Ira] Georgetown Univ, Dept Neurol, Washington, DC USA.
[Oakes, David; Eberly, Shirley] Univ Rochester, Dept Biostat, Rochester, NY USA.
[Zhao, Hongwei] Texas A&M, Dept Epidemiol & Biostat, College Stn, TX USA.
[Romer, Megan] Penn State Univ, Dept Stat, University Pk, PA 16802 USA.
[Young, Anne; Hersch, Steven; Penney, Jack; Rosas, Diana; Novak, Peter; Gusella, James; MacDonald, Marcy] Massachusetts Gen Hosp, Charleston, SC USA.
[Marder, Karen; Fahn, Stanley] Columbia Univ, Med Ctr, Dept Neurol, New York, NY USA.
[Paulsen, Jane] Univ Iowa, Dept Psychiat & Neurol, Iowa City, IA USA.
[Quaid, Kimberly; Wesson, Melissa; Foroud, Tatiana] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
[Siemers, Eric] Lilly Corp Ctr, Indianapolis, IN USA.
[Tanner, Caroline] Parkinsons Inst, Sunnyvale, CA USA.
[Mallonee, William] Hereditary Neurol Dis Ctr, Wichita, KS USA.
[Suter, Greg; Dubinsky, Richard; Gray, Carolyn] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66103 USA.
[Nance, Martha; Bundlie, Scott; Radtke, Dawn] Hennepin Cty Med Ctr, Dept Neurol, Minneapolis, MN 55415 USA.
[Kostyk, Sandra; Baic, Corrine] Ohio State Univ, Dept Neurol, Columbus, OH 43210 USA.
[Caress, James; Walker, Francis; Hunt, Victoria; O'Neill, Christine] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA.
[Chouinard, Sylvain] Hotel Dieu Hosp CHUM, Montreal, PQ, Canada.
[Factor, Stewart; Greenamyre, Timothy; Wood-Siverio, Cathy] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA.
[Corey-Bloom, Jody; Song, David; Peavy, Guerry; Shults, Clifford] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
[Samii, Ali; Bird, Thomas; Lipe, Hillary] Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
[Samii, Ali; Bird, Thomas; Lipe, Hillary] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
[Blindauer, Karen] Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA.
[Caviness, John; Adler, Charles; Duffy, Amy] Mayo Clin Scottsdale, Dept Neurol, Scottsdale, AZ USA.
[Wheelock, Vicki; Tempkin, Teresa; Richman, David] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA.
[Seeberger, Lauren] Idaho Elks Rehabil Hosp, Boise, ID USA.
[Albin, Roger; Chou, Kelvin L.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA.
[Racette, Brad; Perlmutter, Joel S.] Washington Univ, Dept Neurol, St Louis, MO USA.
[Perlman, Susan; Bordelon, Yvette] Univ Calif Los Angeles, Med Ctr, Dept Neurol, Los Angeles, CA 90024 USA.
[Martin, Wayne; Wieler, Marguerite] Univ Alberta, Dept Neurol, Edmonton, AB, Canada.
[Leavitt, Blair; Raymond, Lynn; Decolongon, Joji; Clarke, Lorne] Univ British Columbia, Dept Neurol, Vancouver, BC, Canada.
[Jankovic, Joseph; Hunter, Christine; Klimek, Mary Lou] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA.
[Hauser, Robert A.; Sanchez-Ramos, Juan] Univ S Florida, Dept Neurol, Tampa, FL USA.
[Furtado, Sarah; Suchowersky, Oksana] Univ Calgary, Dept Neurol, Calgary, AB, Canada.
[Guttman, Mark; Sethna, Rustom] Ctr Addict & Mental Hlth, Markham, ON, Canada.
[Feigin, Andrew; Cox, Marie; Shannon, Barbara] North Shore LIJ Univ Hosp, Dept Neurol, Manhasset, NY USA.
[Percy, Alan; Dure, Leon] Univ Alabama Birmingham, Dept Neurobiol, Birmingham, AL USA.
[Harrison, Madaline] Univ Virginia, Dept Neurol, Charlottesville, VA USA.
[Johnson, William] Univ Med & Dent New Jersey, Dept Neurol, Robert Wood Johnson Med Ctr, Stratford, NJ USA.
[Higgins, Donald; Molho, Eric; Nickerson, Constance; Evans, Sharon] Albany Med Coll, Dept Neurol, Albany, NY 12208 USA.
[Hobson, Douglas] Winnipeg Clin, Winnipeg, MB, Canada.
[Singer, Carlos; Galvez-Jimenez, Nestor] Univ Miami, Dept Neurol, Miami, FL USA.
[Shannon, Kathleen; Comella, Cynthia] Rush Univ, Dept Neurol Sci, Chicago, IL 60612 USA.
[Ross, Christopher] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA.
[Saint-Hilaire, Marie H.; Myers, Richard] Boston Univ, Dept Neurol, Boston, MA USA.
[Testa, Claudia; Rosenblatt, Adam] Virginia Commonwealth Univ, Dept Neurol, Richmond, VA 23284 USA.
[Hogarth, Penelope] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
[Weiner, William] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA.
[Como, Peter] US FDA, Rockville, MD 20857 USA.
[Kumar, Rajeev] Rocky Mt Movement Disorders Ctr, Dept Neurol, Denver, CO USA.
[Cotto, Candace] Inst Neurodegenerat Disorders, Dept Neurol, New Haven, CT USA.
[Stout, Julie] Monash Univ, Clin & Cognit Neurosci Lab, Melbourne, Vic, Australia.
RP Biglan, KM (reprint author), Univ Rochester, Dept Neurol, Rochester, NY 14642 USA.
OI Raymond, Lynn/0000-0002-8610-1042
FU National Human Genome Research Institute; National Institutes of Health
NINDS [5RO1-HG-02449]; High Q Foundation/CHDI Foundation, Inc;
Huntington's Disease Society of America; Hereditary Disease Foundation;
Huntington Society of Canada; Fox Family Foundation
FX This research was supported by grants and awards from the National Human
Genome Research Institute and grant 5RO1-HG-02449 from the National
Institutes of Health NINDS (Dr Shoulson), the High Q Foundation/CHDI
Foundation, Inc, the Huntington's Disease Society of America, the
Hereditary Disease Foundation, the Huntington Society of Canada, and the
Fox Family Foundation.
NR 35
TC 1
Z9 1
U1 1
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6149
EI 2168-6157
J9 JAMA NEUROL
JI JAMA Neurol.
PD JAN
PY 2016
VL 73
IS 1
BP 102
EP 110
DI 10.1001/jamaneurol.2015.2736
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA DZ4RZ
UT WOS:000385848500015
ER
PT S
AU Kaneko, KJ
AF Kaneko, K. J.
BE DePamphilis, ML
TI Metabolism of Preimplantation Embryo Development: A Bystander or an
Active Participant?
SO MAMMALIAN PREIMPLANTATION DEVELOPMENT
SE Current Topics in Developmental Biology
LA English
DT Review; Book Chapter
ID PENTOSE-PHOSPHATE PATHWAY; EARLY MOUSE EMBRYO; INNER CELL MASS; YEAST
SACCHAROMYCES-CEREVISIAE; MITOCHONDRIAL QUALITY-CONTROL; PROTEIN-COUPLED
RECEPTOR; SIMPLEX OPTIMIZED MEDIUM; FATTY-ACID OXIDATION;
CANDIDA-ALBICANS; AMINO-ACIDS
AB Unicellular organisms are exquisitely sensitive to nutrient availability in the environment and have evolved elaborate mechanisms to sense the levels and types of nutrients, altering gene expression patterns accordingly to adjust the metabolic activities required to survive. Thus, environmental cues induce adaptive metabolic differentiation through transcriptional and posttranscriptional changes. Similarly, preimplantation embryos are exposed to various environmental cues within the maternal reproductive tract prior to implantation. Because only "simple" culture conditions are required, it is assumed that these embryos are genetically preprogrammed to develop with little influence from the environment, with the exception of few "necessities" provided by the environment. However, a wealth of literature now suggests that the developing embryos are greatly influenced by the maternal environment. Even though the developing embryos have the capacity and plasticity to deal with nutritional imbalance posed by an altered maternal environment, there is often a trade-off to the overall fitness of those embryos later in life. Despite these studies that underline the general importance of the reproductive environment during development, it is thought that the primary driver of mammalian development is strictly genetic and that metabolic adaptation by the preimplantation embryo is secondary to genetic control. In this review, I propose that not only does the maternal environment of developing preimplantation embryos influence developmental potential, pregnancy outcomes, and postnatal disease states, but that it has an active role in induction and potentiation of the first differentiation event, the production of trophectoderm and inner cell mass lineages.
C1 [Kaneko, K. J.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
RP Kaneko, KJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
EM kotaro.kaneko@fda.hhs.gov
NR 232
TC 1
Z9 1
U1 4
U2 4
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0070-2153
BN 978-0-12-801617-6; 978-0-12-801428-8
J9 CURR TOP DEV BIOL
JI Curr. Top. Dev. Biol.
PY 2016
VL 120
BP 259
EP 310
DI 10.1016/bs.ctdb.2016.04.010
PG 52
WC Developmental Biology; Reproductive Biology
SC Developmental Biology; Reproductive Biology
GA BF6UG
UT WOS:000383713000009
PM 27475855
ER
PT J
AU Wright, N
Walters, P
Strang, J
AF Wright, Nat
Walters, Pamela
Strang, John
TI Dual diagnosis in prisons: management of co-existing substance use and
mental health disorders Prevalence of mental ill health in prisons
SO ADVANCES IN DUAL DIAGNOSIS
LA English
DT Editorial Material
ID PSYCHIATRIC-DISORDERS; OUTCOMES; SUICIDE; ENGLAND; COHORT; WALES; RISK;
TC
C1 [Walters, Pamela] SWL & St Georges Mental Hlth Trust, London, England.
[Walters, Pamela] South London & Maudsley Mental Hlth NHS Trust, London, England.
[Strang, John] Kings Coll London, IoPPN, Dept Addict Acad Act, London WC2R 2LS, England.
[Strang, John] KHP AHSC Kings Hlth Partners Acad Hlth Sci Ctr, CAG, London, England.
[Strang, John] South London & Maudsley SLaM NHS Fdn Trust, London, England.
[Strang, John] Kings Coll London, London WC2R 2LS, England.
[Strang, John] WHO, Geneva, Switzerland.
[Strang, John] UNODC, Vienna, Austria.
[Strang, John] US FDA, EMCDDA, Rockville, MD 20857 USA.
[Strang, John] NIDA, Bethesda, MD USA.
RP Walters, P (reprint author), SWL & St Georges Mental Hlth Trust, London, England.; Walters, P (reprint author), South London & Maudsley Mental Hlth NHS Trust, London, England.
EM nat.wright@spectrum-cic.nhs.uk
NR 32
TC 0
Z9 0
U1 1
U2 1
PU EMERALD GROUP PUBLISHING LTD
PI BINGLEY
PA HOWARD HOUSE, WAGON LANE, BINGLEY BD16 1WA, W YORKSHIRE, ENGLAND
SN 1757-0972
EI 2042-8324
J9 ADV DUAL DIAGN
JI Adv. Dual Diagn.
PY 2016
VL 9
IS 1
BP 1
EP 6
DI 10.1108/ADD-12-2015-0025
PG 6
WC Psychology, Clinical
SC Psychology
GA DY0NW
UT WOS:000384794500001
ER
PT J
AU Cai, CZ
Nedosekin, DA
Menyaev, YA
Sarimollaoglu, M
Proskurnin, MA
Zharov, VP
AF Cai, Chengzhong
Nedosekin, Dmitry A.
Menyaev, Yulian A.
Sarimollaoglu, Mustafa
Proskurnin, Mikhail A.
Zharov, Vladimir P.
TI Photoacoustic Flow Cytometry for Single Sickle Cell Detection In Vitro
and In Vivo
SO ANALYTICAL CELLULAR PATHOLOGY
LA English
DT Article
ID DIAGNOSIS; HEMOGLOBINOPATHIES; DISEASE; BLOOD; MICE
AB Control of sickle cell disease (SCD) stage and treatment efficiency are still time-consuming which makes well-timed prevention of SCD crisis difficult. We show here that in vivo photoacoustic (PA) flow cytometry (PAFC) has a potential for real-time monitoring of circulating sickled cells in mouse model. In vivo data were verified by in vitro PAFC and photothermal (PT) and PA spectral imaging of sickle red blood cells (sRBCs) expressing SCD-associated hemoglobin (HbS) compared to normal red blood cells (nRBCs). We discovered that PT and PA signal amplitudes from sRBCs in linear mode were 2-4-fold lower than those from nRBCs. PT and PA imaging revealed more profound spatial hemoglobin heterogeneity in sRBCs than in nRBCs, which can be associated with the presence of HbS clusters with high local absorption. This hypothesis was confirmed in nonlinear mode through nanobubble formation around overheated HbS clusters accompanied by spatially selective signal amplification. More profound differences in absorption of sRBCs than in nRBCs led to notable increase in PA signal fluctuation (fluctuation PAFC mode) as an indicator of SCD. The obtained data suggest that noninvasive label-free fluctuation PAFC has a potential for real-time enumeration of sRBCs both in vitro and in vivo.
C1 [Cai, Chengzhong; Nedosekin, Dmitry A.; Menyaev, Yulian A.; Sarimollaoglu, Mustafa; Zharov, Vladimir P.] Univ Arkansas Med Sci, Arkansas Nanomed Ctr, Little Rock, AR 72205 USA.
[Cai, Chengzhong] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Proskurnin, Mikhail A.] Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119991, Russia.
RP Zharov, VP (reprint author), Univ Arkansas Med Sci, Arkansas Nanomed Ctr, Little Rock, AR 72205 USA.
EM zharovvladimirp@uams.edu
RI Proskurnin, Mikhail/E-9704-2011;
OI Proskurnin, Mikhail/0000-0001-5577-6883; Menyaev,
Yulian/0000-0001-5861-3641
FU National Institute of Health [R01CA131164, R01EB009230]; National
Science Foundation [DB-155606085, OIA-1457888]; Russian Foundation for
Basic Research [14-04-01361a, 16-03-01089a]
FX This work was supported in part by the National Institute of Health
(Grants R01CA131164 and R01EB009230), by the National Science Foundation
(Grants DB-155606085 and OIA-1457888), and by the Russian Foundation for
Basic Research (Grants 14-04-01361a and 16-03-01089a), The authors are
thankful to Mr. Kai Carey (Arkansas Nanomedicine Center, University of
Arkansas for Medical Sciences, Little Rock, USA) for the proofreading.
NR 31
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Z9 1
U1 4
U2 4
PU HINDAWI PUBLISHING CORP
PI NEW YORK
PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA
SN 2210-7177
EI 2210-7185
J9 ANAL CELL PATHOL
JI Anal. Cell. Pathol.
PY 2016
AR 2642361
DI 10.1155/2016/2642361
PG 11
WC Oncology; Cell Biology; Pathology
SC Oncology; Cell Biology; Pathology
GA DY5KW
UT WOS:000385139500001
ER
PT J
AU Hursh, DA
Stultz, BG
Park, SY
AF Hursh, Deborah A.
Stultz, Brian G.
Park, Sung Yeon
TI Jun N-terminal kinase signaling makes a face
SO FLY
LA English
DT Article
DE Bone Morphogenetic Protein (BMP); decapentaplegic (dpp); Drosophila;
head morphogenesis; Jun N-terminal Kinase (JNK)
ID DROSOPHILA WING DISC; CIS-REGULATORY REGION; DECAPENTAPLEGIC GENE;
IMAGINAL DISCS; GROWTH-CONTROL; ADULT HEAD; DEVELOPMENTAL ANALYSIS;
EPITHELIAL-CELLS; THORAX CLOSURE; VENTRAL HEAD
AB decapentaplegic (dpp), the Drosophila ortholog of BMP 2/4, directs ventral adult head morphogenesis through expression in the peripodial epithelium of the eye-antennal disc. This dpp expressing domain exerts effects both on the peripodial epithelium, and the underlying disc proper epithelium. We have uncovered a role for the Jun N-terminal kinase (JNK) pathway in dpp-mediated ventral head development. JNK activity is required for dpp's action on the disc proper, but in the absence of dpp expression, excessive JNK activity is produced, leading to specific loss of maxillary palps. In this review we outline our hypotheses on how dpp acts by both short range and longer range mechanisms to direct head morphogenesis and speculate on the dual role of JNK signaling in this process. Finally, we describe the regulatory control of dpp expression in the eye-antennal disc, and pose the problem of how the various expression domains of a secreted protein can be targeted to their specific functions.
C1 [Hursh, Deborah A.; Stultz, Brian G.] US FDA, Div Cell & Gene Therapies, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave,Bldg 52-72,Rm 3216, Silver Spring, MD 20993 USA.
[Park, Sung Yeon] Seoul Natl Univ, Coll Med, Dept Physiol, Ischem Hypox Dis Inst, Seoul, South Korea.
RP Hursh, DA (reprint author), US FDA, Div Cell & Gene Therapies, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave,Bldg 52-72,Rm 3216, Silver Spring, MD 20993 USA.
EM deborah.hursh@fda.hhs.gov
NR 56
TC 0
Z9 0
U1 2
U2 2
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1933-6934
EI 1933-6942
J9 FLY
JI Fly
PY 2016
VL 10
IS 4
BP 195
EP 203
DI 10.1080/19336934.2016.1207012
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DX8XY
UT WOS:000384676400006
PM 27384866
ER
PT J
AU Gamalo-Siebers, M
Gao, AJ
Lakshminarayanan, M
Liu, GH
Natanegara, F
Railkar, R
Schmidli, H
Song, GC
AF Gamalo-Siebers, Margaret
Gao, Aijun
Lakshminarayanan, Mani
Liu, Guanghan
Natanegara, Fanni
Railkar, Radha
Schmidli, Heinz
Song, Guochen
TI Bayesian methods for the design and analysis of noninferiority trials
SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS
LA English
DT Article
DE Bayesian inference; clinical trial; meta-analysis; noninferiority
ID NON-INFERIORITY TRIALS; ACTIVE-CONTROL TRIALS; HISTORICAL CONTROL
INFORMATION; SAMPLE-SIZE CALCULATIONS; CLINICAL-TRIALS;
STATISTICAL-METHODS; BINARY OUTCOMES; END-POINTS; PLACEBO; PROPORTIONS
AB The gold standard for evaluating treatment efficacy of a medical product is a placebo-controlled trial. However, when the use of placebo is considered to be unethical or impractical, a viable alternative for evaluating treatment efficacy is through a noninferiority (NI) study where a test treatment is compared to an active control treatment. The minimal objective of such a study is to determine whether the test treatment is superior to placebo. An assumption is made that if the active control treatment remains efficacious, as was observed when it was compared against placebo, then a test treatment that has comparable efficacy with the active control, within a certain range, must also be superior to placebo. Because of this assumption, the design, implementation, and analysis of NI trials present challenges for sponsors and regulators. In designing and analyzing NI trials, substantial historical data are often required on the active control treatment and placebo. Bayesian approaches provide a natural framework for synthesizing the historical data in the form of prior distributions that can effectively be used in design and analysis of a NI clinical trial. Despite a flurry of recent research activities in the area of Bayesian approaches in medical product development, there are still substantial gaps in recognition and acceptance of Bayesian approaches in NI trial design and analysis. The Bayesian Scientific Working Group of the Drug Information Association provides a coordinated effort to target the education and implementation issues on Bayesian approaches for NI trials. In this article, we provide a review of both frequentist and Bayesian approaches in NI trials, and elaborate on the implementation for two common Bayesian methods including hierarchical prior method and meta-analytic-predictive approach. Simulations are conducted to investigate the properties of the Bayesian methods, and some real clinical trial examples are presented for illustration.
C1 [Gamalo-Siebers, Margaret] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
[Gao, Aijun] InVent Hlth Clin, Princeton, NJ USA.
[Lakshminarayanan, Mani; Railkar, Radha] Pfizer Inc, Biotechnol Clin Dev Stat, Collegeville, PA 19426 USA.
[Liu, Guanghan] Merck Sharp & Dohme Corp, N Wales, PA USA.
[Natanegara, Fanni] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Schmidli, Heinz] Novartis Pharma AG, Basel, Switzerland.
[Song, Guochen] Quintiles, Durham, NC USA.
RP Lakshminarayanan, M (reprint author), Pfizer Inc, Biotechnol Clin Dev Stat, Collegeville, PA 19426 USA.
EM Mani.Lakshminarayan@pfizer.com
NR 52
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Z9 1
U1 3
U2 3
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1054-3406
EI 1520-5711
J9 J BIOPHARM STAT
JI J. Biopharm. Stat.
PY 2016
VL 26
IS 5
BP 823
EP 841
DI 10.1080/10543406.2015.1074920
PG 19
WC Pharmacology & Pharmacy; Statistics & Probability
SC Pharmacology & Pharmacy; Mathematics
GA DX5SQ
UT WOS:000384442400003
PM 26247350
ER
PT J
AU Liu, Y
Upadhyaya, B
Fardin-Kia, AR
Juenemann, RM
Dey, M
AF Liu, Yi
Upadhyaya, Bijaya
Fardin-Kia, Ali Reza
Juenemann, Robert M.
Dey, Moul
TI Dietary resistant starch type 4-derived butyrate attenuates nuclear
factor-kappa-B1 through modulation of histone H3 trimethylation at
lysine 27
SO FOOD & FUNCTION
LA English
DT Article
ID CHAIN FATTY-ACIDS; NF-KAPPA-B; INTESTINAL EPITHELIAL-CELLS; REGULATORY
T-CELLS; GUT MICROBIOTA; ENERGY-METABOLISM; SODIUM-BUTYRATE;
GENE-EXPRESSION; UP-REGULATION; IL-10
AB Indigestible resistant starches (RS) are substrates for gut-microbial metabolism and have been shown to attenuate intestinal inflammation but the supporting evidence is inconsistent and lacks mechanistic explanation. We have recently reported dietary RS type 4 (RS4) induced improvements in immunometabolic functions in humans and a concomitant increase in butyrogenic gut-bacteria. Since inflammation is a key component in metabolic diseases, here we investigated the effects of RS4-derived butyrate on the epigenetic repression of pro-inflammatory genes in vivo and in vitro. RS4-fed mice, compared to the controldiet group, had higher cecal butyrate and increased tri-methylation of lysine 27 on histone 3 (H3K27me3) in the promoter of nuclear factor-kappa-B1 (NF kappa B1) in the colon tissue. The H3K27me3-enrichment inversely correlated with the concentration dependent down-regulation of NF kappa B1 in sodium butyrate treated human colon epithelial cells. Two additional inflammatory genes were attenuated by sodium butyrate, but were not linked with H3K27me3 changes. This exploratory study presents a new opportunity for studying underlying H3K27me3 and other methylation modifying mechanisms linked to RS4 biological activity.
C1 [Liu, Yi; Upadhyaya, Bijaya; Juenemann, Robert M.; Dey, Moul] South Dakota State Univ, Dept Hlth & Nutr Sci, Box 2203, Brookings, SD 57007 USA.
[Fardin-Kia, Ali Reza] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, HFS 717, College Pk, MD 20740 USA.
RP Dey, M (reprint author), South Dakota State Univ, Dept Hlth & Nutr Sci, Box 2203, Brookings, SD 57007 USA.
EM Moul.Dey@sdstate.edu
FU MGP Ingredients Inc., Atchison KS [3P2662]; USDA National Institute of
Food and Agriculture [Hatch] [1004817]; National Institutes of Health
[R00AT4245]
FX This work was supported by MGP Ingredients Inc., Atchison KS [3P2662],
the USDA National Institute of Food and Agriculture [Hatch 1004817], and
the National Institutes of Health [R00AT4245] to M.D.
NR 49
TC 0
Z9 0
U1 2
U2 2
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 2042-6496
EI 2042-650X
J9 FOOD FUNCT
JI Food Funct.
PY 2016
VL 7
IS 9
BP 3772
EP 3781
DI 10.1039/c6fo00856a
PG 10
WC Biochemistry & Molecular Biology; Food Science & Technology
SC Biochemistry & Molecular Biology; Food Science & Technology
GA DX3DS
UT WOS:000384254100012
PM 27713965
ER
PT J
AU Yu, H
Zeng, J
Li, YH
Thon, V
Shi, BJ
Chen, X
AF Yu, Hai
Zeng, Jie
Li, Yanhong
Thon, Vireak
Shi, Baojun
Chen, Xi
TI Effective one-pot multienzyme (OPME) synthesis of monotreme milk
oligosaccharides and other sialosides containing 4-O-acetyl sialic acid
SO ORGANIC & BIOMOLECULAR CHEMISTRY
LA English
DT Article
ID EFFICIENT CHEMOENZYMATIC SYNTHESIS; INFLUENZA-VIRUS INFECTION;
SUBSTRATE-SPECIFICITY; SIALYLTRANSFERASE;
BETA-1-4-GALACTOSYLTRANSFERASES; PROMISCUITY; FLEXIBILITY; DERIVATIVES;
DIVERSITY; LIBRARIES
AB A facile one-pot two-enzyme chemoenzymatic approach has been established for the gram (Neu4,5Ac(2)alpha 3Lac, 1.33 g) and preparative scale (Neu4,5Ac(2)alpha 3LNnT) synthesis of monotreme milk oligosaccharides. Other O-acetyl-5-N-acetylneuraminic acid (Neu4,5Ac(2))-or 4-O-acetyl-5-N-glycolylneuraminic acid (Neu4Ac5Gc) -containing alpha 2-3-sialosides have also been synthesized in the preparative scale. Used as an effective probe, Neu4,5Ac(2 alpha)3Gal beta rho NP was found to be a suitable substrate by human influenza A viruses but not bacterial sialidases.
C1 [Yu, Hai; Zeng, Jie; Li, Yanhong; Thon, Vireak; Shi, Baojun; Chen, Xi] Univ Calif Davis, Dept Chem, One Shields Ave, Davis, CA 95616 USA.
[Zeng, Jie] Henan Inst Sci & Technol, Sch Food Sci, Xinxiang 453003, Henan, Peoples R China.
[Shi, Baojun] Northwest A&F Univ, Coll Plant Protect, Yangling 712100, Shaanxi, Peoples R China.
[Thon, Vireak] US FDA, Lab Bacterial Polysaccharides, Bethesda, MD 20892 USA.
RP Chen, X (reprint author), Univ Calif Davis, Dept Chem, One Shields Ave, Davis, CA 95616 USA.
EM xiichen@ucdavis.edu
FU US NIH [R01HD065122, R01GM076360- 04S1, U01CA199792]; China Scholarship
Council; NSF [DBIO-722538]
FX This work was supported by US NIH grants R01HD065122, R01GM076360- 04S1
(to X. C.), and U01CA199792 (to A. V.) as well as scholarships from the
China Scholarship Council (to J. Z. and B. S.). A Bruker Avance-800 NMR
spectrometer was funded by NSF grant DBIO-722538. We would like to thank
Professor Nicole Baumgarth at the University of California-Davis for
providing purified human influenza viruses as kind gifts. H. Y., Y. L.,
and X. C. are co-founders of Glycohub, Inc., a company focused on the
development of carbohydrate-based reagents, diagnostics, and
therapeutics. Glycohub, Inc. played no role in the design, execution,
interpretation, or publication of this study.
NR 51
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U1 3
U2 3
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1477-0520
EI 1477-0539
J9 ORG BIOMOL CHEM
JI Org. Biomol. Chem.
PY 2016
VL 14
IS 36
BP 8586
EP 8597
DI 10.1039/c6ob01706a
PG 12
WC Chemistry, Organic
SC Chemistry
GA DX3YF
UT WOS:000384313100022
PM 27548611
ER
PT S
AU Hammer, DX
Lozzi, A
Boretsky, A
Agrawal, A
Welle, CG
AF Hammer, Daniel X.
Lozzi, Andrea
Boretsky, Adam
Agrawal, Anant
Welle, Cristin G.
BE Madsen, SJ
Yang, VXD
Jansen, ED
Luo, Q
Ding, J
Roe, AW
Mohanty, SK
Thakor, NV
TI Acute changes associated with electrode insertion measured with optical
coherence microscopy
SO CLINICAL AND TRANSLATIONAL NEUROPHOTONICS; NEURAL IMAGING AND SENSING;
AND OPTOGENETICS AND OPTICAL MANIPULATION
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Clinical and Translational Neurophotonics; Neural Imaging
and Sensing; and Optogenetics and Optical Manipulation
CY FEB 13-16, 2016
CL San Francisco, CA
SP SPIE
DE Optical coherence microscopy; angiography; neurophotonics; capillary
velocimetry; brain-computer interface; penetrating neural electrodes;
neuroinflammatory response; cortical window model
ID DOPPLER; ANGIOGRAPHY; TOMOGRAPHY; CONTRAST; TISSUE; BRAIN; OCT
AB Despite advances in functional neural imaging, penetrating microelectrodes provide the most direct interface for the extraction of neural signals from the nervous system and are a critical component of many high degree-of-freedom brain-computer interface devices. Electrode insertion is a traumatic event that elicits a complex neuroinflammatory response. In this investigation we applied optical coherence microscopy (OCM), particularly optical coherence angiography (OCA), to characterize the immediate tissue response during microelectrode insertion. Microelectrodes of varying dimension and footprint (one-, two-, and four-shank) were inserted into mouse motor cortex beneath a window after craniotomy surgery. The microelectrodes were inserted in 3-4 steps at 15-20 degrees, with approximately 250 mu m linear insertion distance for each step. Before insertion and between each step, OCM datasets were collected, including for quantitative capillary velocimetry. A cohort of control animals without microelectrode insertion was also imaged over a similar time period (2-3 hours). Mechanical tissue deformation was observed in all the experimental animals. The quantitative angiography results varied across animals, and were not correlated with device dimensions. In some cases, localized flow drop-out was observed in a small region surrounding the electrode, while in other instances a global disruption in flow occurred, perhaps as a result of large vessel compression caused by mechanical pressure. OCM is a tool that can be used in various neurophotonics applications, including quantification of the neuroinflammatory response to penetrating electrode insertion.
C1 [Hammer, Daniel X.; Lozzi, Andrea; Boretsky, Adam; Agrawal, Anant; Welle, Cristin G.] US FDA, Div Biomed Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10913 New Hampshire Ave, Silver Spring, MD 20993 USA.
RP Hammer, DX (reprint author), US FDA, Div Biomed Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10913 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM daniel.hammer@fda.hhs.gov
NR 19
TC 0
Z9 0
U1 0
U2 0
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-62841-960-3
J9 PROC SPIE
PY 2016
VL 9690
AR UNSP 96901B
DI 10.1117/12.2213073
PG 8
WC Neuroimaging; Optics; Physics, Applied; Radiology, Nuclear Medicine &
Medical Imaging
SC Neurosciences & Neurology; Optics; Physics; Radiology, Nuclear Medicine
& Medical Imaging
GA BF6KU
UT WOS:000383224700017
ER
PT S
AU Vasudevan, S
Kumsa, D
Takmakov, P
Welle, CG
Hammer, DX
AF Vasudevan, Srikanth
Kumsa, Doe
Takmakov, Pavel
Welle, Cristin G.
Hammer, Daniel X.
BE Madsen, SJ
Yang, VXD
Jansen, ED
Luo, Q
Ding, J
Roe, AW
Mohanty, SK
Thakor, NV
TI Real Time Imaging of Peripheral Nerve Vasculature Using Optical
Coherence Angiography
SO CLINICAL AND TRANSLATIONAL NEUROPHOTONICS; NEURAL IMAGING AND SENSING;
AND OPTOGENETICS AND OPTICAL MANIPULATION
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Clinical and Translational Neurophotonics; Neural Imaging
and Sensing; and Optogenetics and Optical Manipulation
CY FEB 13-16, 2016
CL San Francisco, CA
SP SPIE
DE Peripheral nerves; OCT; angiography; electrical stimulation;
neuromodulation
ID ELECTRICAL-STIMULATION; FUNCTIONAL-EVALUATION; RAT; VASOCONSTRICTION;
MODEL
AB The peripheral nervous system (PNS) carries bidirectional information between the central nervous system and distal organs. PNS stimulation has been widely used in medical devices for therapeutic indications, such as bladder control and seizure cessation. Investigational uses of PNS stimulation include providing sensory feedback for improved control of prosthetic limbs. While nerve safety has been well documented for stimulation parameters used in marketed devices, novel PNS stimulation devices may require alternative stimulation paradigms to achieve maximum therapeutic benefit. Improved testing paradigms to assess the safety of stimulation will expedite the development process for novel PNS stimulation devices. The objective of this research is to assess peripheral nerve vascular changes in real-time with optical coherence angiography (OCA). A 1300-nm OCA system was used to image vasculature changes in the rat sciatic nerve in the region around a surface contacting single electrode. Nerves and vasculature were imaged without stimulation for 180 minutes to quantify resting blood vessel diameter. Walking track analysis was used to assess motor function before and 6 days following experiments. There was no significant change in vessel diameter between baseline and other time points in all animals. Motor function tests indicated the experiments did not impair functionality. We also evaluated the capabilities to image the nerve during electrical stimulation in a pilot study. Combining OCA with established nerve assessment methods can be used to study the effects of electrical stimulation safety on neural and vascular tissue in the periphery.
C1 [Vasudevan, Srikanth; Kumsa, Doe; Takmakov, Pavel; Welle, Cristin G.; Hammer, Daniel X.] US FDA, CDRH, OSEL, Silver Spring, MD 20993 USA.
[Welle, Cristin G.] Univ Colorado Denver, Dept Neurosurg, Aurora, CO USA.
[Kumsa, Doe] Med Device Innovat Consortium, St Louis Pk, MN USA.
RP Vasudevan, S (reprint author), US FDA, CDRH, OSEL, Silver Spring, MD 20993 USA.
OI Takmakov, Pavel/0000-0001-6591-0257
NR 14
TC 0
Z9 0
U1 0
U2 0
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-62841-960-3
J9 PROC SPIE
PY 2016
VL 9690
AR UNSP 96901D
DI 10.1117/12.2213160
PG 7
WC Neuroimaging; Optics; Physics, Applied; Radiology, Nuclear Medicine &
Medical Imaging
SC Neurosciences & Neurology; Optics; Physics; Radiology, Nuclear Medicine
& Medical Imaging
GA BF6KU
UT WOS:000383224700018
ER
PT S
AU Wang, JT
Huang, S
Myers, M
Chen, Y
Welle, C
Pfefer, J
AF Wang, Jianting
Huang, Stanley
Myers, Matthew
Chen, Yu
Welle, Cristin
Pfefer, Joshua
BE Madsen, SJ
Yang, VXD
Jansen, ED
Luo, Q
Ding, J
Roe, AW
Mohanty, SK
Thakor, NV
TI Elucidation of the role of biological factors and device design in
cerebral NIRS using an in vivo hematoma model based on highintensity
focused ultrasound
SO CLINICAL AND TRANSLATIONAL NEUROPHOTONICS; NEURAL IMAGING AND SENSING;
AND OPTOGENETICS AND OPTICAL MANIPULATION
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Clinical and Translational Neurophotonics; Neural Imaging
and Sensing; and Optogenetics and Optical Manipulation
CY FEB 13-16, 2016
CL San Francisco, CA
SP SPIE
DE Near-infrared spectroscopy (NIRS); high-intensity focused ultrasound
(HIFU); hematoma detection; traumatic brain injury (TBI); murine TBI
model
ID TRAUMATIC BRAIN-INJURY; NEAR-INFRARED SPECTROSCOPY; HEMORRHAGE
AB Near-Infrared Spectroscopy (NIRS) is an emerging medical countermeasure for rapid, field detection of hematomas caused by traumatic brain injury (TBI). Bench and animal tests to determine NIRS sensitivity and specificity are needed. However, current animal models involving non-invasively induced, localized neural damage are limited. We investigated an in vivo murine hematoma model in which cerebral hemorrhage was induced noninvasively by high-intensity focused ultrasound (HIFU) with calibrated positioning and parameters. To characterize the morphology of induced hematomas, we used skull-intact histological evaluation. A multi-wavelength fiberoptic NIRS system with three source-detector separation distances was used to detect hematoma A 1.1 MHz transducer produced consistent small-to-medium hematoma localized to a single hemisphere, along with bruising of the scalp, with a low mortality rate. A 220 kHz transducer produced larger, more diffuse hematomas, with higher variability in size and a correspondingly higher mortality rate. No skin bruising or blood accumulation between the skin and skull was observed following injury application with the 220 kHz transducer. Histological analysis showed higher sensitivity for larger hematomas (>4x4 mm(2)). NIRS optical density change after HIFU was able to detect all hematomas, with sensitivity dependent on wavelength and separation distance. While improvements in methods for validating cerebral blood distribution are needed, the HIFU hematoma model provided useful insights that will inform development of biologically relevant, performance test methods for cerebral NIRS systems.
C1 [Wang, Jianting; Huang, Stanley; Myers, Matthew; Welle, Cristin; Pfefer, Joshua] US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20093 USA.
[Chen, Yu] Univ Maryland, Fischell Dept Bioengn, Jeong H Kim Engn Bldg 2330, College Pk, MD 20742 USA.
RP Pfefer, J (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20093 USA.
EM Joshua.Pfefer@fda.hhs.gov
NR 19
TC 0
Z9 0
U1 0
U2 0
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-62841-960-3
J9 PROC SPIE
PY 2016
VL 9690
AR UNSP 96900U
DI 10.1117/12.2217771
PG 8
WC Neuroimaging; Optics; Physics, Applied; Radiology, Nuclear Medicine &
Medical Imaging
SC Neurosciences & Neurology; Optics; Physics; Radiology, Nuclear Medicine
& Medical Imaging
GA BF6KU
UT WOS:000383224700011
ER
PT J
AU Mossoba, ME
Flynn, TJ
Vohra, S
Wiesenfeld, P
Sprando, RL
AF Mossoba, Miriam E.
Flynn, Thomas J.
Vohra, Sanah
Wiesenfeld, Paddy
Sprando, Robert L.
TI Evaluation of "Dream Herb," Calea zacatechichi, for Nephrotoxicity Using
Human Kidney Proximal Tubule Cells
SO JOURNAL OF TOXICOLOGY
LA English
DT Article
ID NF-KAPPA-B; SESQUITERPENE LACTONES; DIABETIC-NEPHROPATHY;
MOLECULAR-STRUCTURE; PLANTS; BIOMARKERS; HK-2; FLAVONOIDS; TOXICITY;
INJURY
AB A recent surge in the use of dietary supplements, including herbal remedies, necessitates investigations into their safety profiles. "Dream herb," Calea zacatechichi, has long been used in traditional folk medicine for a variety of purposes and is currently being marketed in the US for medicinal purposes, including diabetes treatment. Despite the inherent vulnerability of the renal system to xenobiotic toxicity, there is a lack of safety studies on the nephrotoxic potential of this herb. Additionally, the high frequency of diabetes-associated kidney disease makes safety screening of C. zacatechichi for safety especially important. We exposed human proximal tubuleHK-2 cells to increasing doses of this herb alongside known toxicant and protectant control compounds to examine potential toxicity effects of C. zacatechichi relative to control compounds. We evaluated both cellular and mitochondrial functional changes related to toxicity of this dietary supplement and found that even at low doses evidence of cellular toxicity was significant. Moreover, these findings correlated with significantly elevated levels of nephrotoxicity biomarkers, lending further support for the need to further scrutinize the safety of this herbal dietary supplement.
C1 [Mossoba, Miriam E.; Flynn, Thomas J.; Vohra, Sanah; Wiesenfeld, Paddy; Sprando, Robert L.] US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Toxicol,NIVTB, 8301 Muirkirk Rd, Laurel, MD 20708 USA.
RP Mossoba, ME (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Toxicol,NIVTB, 8301 Muirkirk Rd, Laurel, MD 20708 USA.
EM miriam.mossoba@fda.hhs.gov
NR 52
TC 1
Z9 1
U1 2
U2 2
PU HINDAWI PUBLISHING CORP
PI NEW YORK
PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA
SN 1687-8191
EI 1687-8205
J9 J TOXICOL
JI J. Toxicol.
PY 2016
AR 9794570
DI 10.1155/2016/9794570
PG 7
WC Toxicology
SC Toxicology
GA DX1LX
UT WOS:000384130000001
ER
PT J
AU Atienzar, FA
Blomme, EA
Chen, MJ
Hewitt, P
Kenna, JG
Labbe, G
Moulin, F
Pognan, F
Roth, AB
Suter-Dick, L
Ukairo, O
Weaver, RJ
Will, Y
Dambach, DM
AF Atienzar, Franck A.
Blomme, Eric A.
Chen, Minjun
Hewitt, Philip
Kenna, J. Gerry
Labbe, Gilles
Moulin, Frederic
Pognan, Francois
Roth, Adrian B.
Suter-Dick, Laura
Ukairo, Okechukwu
Weaver, Richard J.
Will, Yvonne
Dambach, Donna M.
TI Key Challenges and Opportunities Associated with the Use of In Vitro
Models to Detect Human DILI: Integrated Risk Assessment and Mitigation
Plans
SO BIOMED RESEARCH INTERNATIONAL
LA English
DT Review
ID INDUCED LIVER-INJURY; DRUG-INDUCED HEPATOTOXICITY; PRIMARY HUMAN
HEPATOCYTES; SALT EXPORT PUMP; INDUCED MITOCHONDRIAL DYSFUNCTION;
MICROARRAY EXPERIMENT MIAME; HEPATOMA HEPARG CELLS; HEPG2 CELLS; ORAL
MEDICATIONS; RAT HEPATOCYTES
AB Drug-induced liver injury (DILI) is a major cause of late-stage clinical drug attrition, market withdrawal, black-box warnings, and acute liver failure. Consequently, it has been an area of focus for toxicologists and clinicians for several decades. In spite of considerable efforts, limited improvements in DILI prediction have been made and efforts to improve existing preclinical models or develop new test systems remain a high priority. While prediction of intrinsic DILI has improved, identifying compounds with a risk for idiosyncratic DILI (iDILI) remains extremely challenging because of the lack of a clear mechanistic understanding and the multifactorial pathogenesis of idiosyncratic drug reactions. Well-defined clinical diagnostic criteria and risk factors are also missing. This paper summarizes key data interpretation challenges, practical considerations, model limitations, and the need for an integrated risk assessment. As demonstrated through selected initiatives to address other types of toxicities, opportunities exist however for improvement, especially through better concerted efforts at harmonization of current, emerging and novel in vitro systems or through the establishment of strategies for implementation of preclinical DILI models across the pharmaceutical industry. Perspectives on the incorporation of newer technologies and the value of precompetitive consortia to identify useful practices are also discussed.
C1 [Atienzar, Franck A.] UCB BioPharma SPRL, Chemin Foriest,R9 Bldg, B-1420 Braine Lalleud, Belgium.
[Blomme, Eric A.] AbbVie, 1 North Waukegan Rd, N Chicago, IL 60064 USA.
[Chen, Minjun] US Food & Drug Adm FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA.
[Hewitt, Philip] Merck KGaA, Frankfurter Str 250, D-64293 Darmstadt, Germany.
[Kenna, J. Gerry] Drug Safety Consultant, Macclesfield SK11, Cheshire, England.
[Labbe, Gilles] Sanofi, Batiment C Bernard,13 Quai Jules Guesdes,Zone B, F-94403 Vitry Sur Seine 94403, France.
[Moulin, Frederic] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Pognan, Francois] Novartis Pharma AG, Klybeckstr 141, CH-4057 Basel, Switzerland.
[Roth, Adrian B.] Hoffmann La Roche AG, CH-4000 Basel, Switzerland.
[Suter-Dick, Laura] Univ Appl Sci Northwestern Switzerland, Sch Life Sci, Grundenstr 40, CH-4132 Muttenz, Switzerland.
[Ukairo, Okechukwu] Ipsen Biosci Inc, 650 E Kendall St, Cambridge, MA 02142 USA.
[Weaver, Richard J.] IRIS, 50 Rue Carnot, F-92284 Suresnes, France.
[Will, Yvonne] Pfizer R&D, Drug Safety Res & Dev, Eastern Point Rd, Groton, CT 06340 USA.
[Dambach, Donna M.] Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA.
RP Atienzar, FA (reprint author), UCB BioPharma SPRL, Chemin Foriest,R9 Bldg, B-1420 Braine Lalleud, Belgium.
EM franck.atienzar@ucb.com
NR 168
TC 0
Z9 0
U1 2
U2 2
PU HINDAWI PUBLISHING CORP
PI NEW YORK
PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA
SN 2314-6133
EI 2314-6141
J9 BIOMED RES INT
JI Biomed Res. Int.
PY 2016
AR 9737920
DI 10.1155/2016/9737920
PG 20
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA DW3AI
UT WOS:000383513800001
ER
PT J
AU Weininger, S
Jaffe, MB
Robkin, M
Rausch, T
Arney, D
Goldman, JM
AF Weininger, Sandy
Jaffe, Michael B.
Robkin, Michael
Rausch, Tracy
Arney, David
Goldman, Julian M.
TI The Importance of State and Context in Safe Interoperable Medical
Systems
SO IEEE JOURNAL OF TRANSLATIONAL ENGINEERING IN HEALTH AND MEDICINE-JTEHM
LA English
DT Article
DE Safety; interoperability; state; context
AB This paper describes why "device state" and "patient context" information are necessary components of device models for safe interoperability. This paper includes a discussion of the importance of describing the roles of devices with respect to interactions (including human user workflows involving devices, and device to device communication) within a system, particularly those intended for use at the point-of-care, and how this role information is communicated. In addition, it describes the importance of clinical scenarios in creating device models for interoperable devices.
C1 [Weininger, Sandy] FDA CDRH, Off Sci & Engn Labs, Silver Spring, MD 20993 USA.
[Jaffe, Michael B.; Arney, David; Goldman, Julian M.] Massachusetts Gen Hosp, Dept Anesthesia, MDPnP Program, Boston, MA 02114 USA.
[Robkin, Michael] Anakena Solut Inc, Woodland Hills, CA 91367 USA.
[Rausch, Tracy] DocBox Inc, Newton, MA 02460 USA.
RP Weininger, S (reprint author), FDA CDRH, Off Sci & Engn Labs, Silver Spring, MD 20993 USA.
EM sandy.weininger@fda.hhs.gov
NR 24
TC 1
Z9 1
U1 0
U2 0
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2168-2372
J9 IEEE J TRANSL ENG HE
JI IEEE J. Transl. Eng. Health Med.-JTEHM
PY 2016
VL 4
AR 2800110
DI 10.1109/JTEHM.2016.2596283
PG 10
WC Engineering, Biomedical
SC Engineering
GA DV2TZ
UT WOS:000382775900001
PM 27730013
ER
PT J
AU O'Donoghue, AC
Sullivan, HW
Williams, PA
Squire, C
Betts, KR
Willoughby, JF
Parvanta, S
AF O'Donoghue, Amie C.
Sullivan, Helen W.
Williams, Pamela A.
Squire, Claudia
Betts, Kevin R.
Willoughby, Jessica Fitts
Parvanta, Sarah
TI Consumers' Understanding of FDA Approval Requirements and Composite
Scores in Direct-to-Consumer Prescription Drug Print Ads
SO JOURNAL OF HEALTH COMMUNICATION
LA English
DT Article
ID EFFICACY INFORMATION; RANDOMIZED-TRIAL; BENEFITS; ADVERTISEMENTS; HARMS
AB In 2 studies, we investigated how laypersons perceive the Food and Drug Administration (FDA) approval process, FDA authority, and the presentation of composite scores in direct-to-consumer (DTC) prescription drug print ads. The 1st study consisted of 4 focus groups (N=38) in 2 cities. Using a semi-structured guide, a moderator led participants through the viewing of 3 existing DTC print ads that differed in the presence or absence of composite score information, and participants discussed their views of the ads and their understanding of composite scores. The 2nd study surveyed a nationally representative sample of 1,629 individuals from the general population who saw a fictitious DTC print ad and answered closed-ended questions about the same topics. Results showed that knowledge of FDA approval and authority was mixed, with several misconceptions apparent. Many consumers were not familiar with the use of composite scores in a medical context or in advertising and, in the 1st study, expressed distrust of the product and the ad after learning about how composite scores are used. In the 2nd study, receiving composite score information changed the perceived clarity of the ad but not the perceived risk or benefits. Implications for the presentation of complex medical information are discussed.
C1 [O'Donoghue, Amie C.; Sullivan, Helen W.; Betts, Kevin R.] US FDA, 10903 New Hampshire Ave,Bldg 51,Room 3236, Silver Spring, MD 10993 USA.
[Williams, Pamela A.; Squire, Claudia; Willoughby, Jessica Fitts; Parvanta, Sarah] RTI Int Inc, Res Triangle Pk, NC USA.
RP O'Donoghue, AC (reprint author), US FDA, 10903 New Hampshire Ave,Bldg 51,Room 3236, Silver Spring, MD 10993 USA.
EM amie.odonoghue@fda.hhs.gov
OI Willoughby, Jessica/0000-0002-1118-9502
NR 24
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1081-0730
EI 1087-0415
J9 J HEALTH COMMUN
JI J. Health Commun.
PY 2016
VL 21
IS 8
BP 927
EP 934
DI 10.1080/10810730.2016.1179367
PG 8
WC Communication; Information Science & Library Science
SC Communication; Information Science & Library Science
GA DU6LD
UT WOS:000382325300006
PM 27414000
ER
PT J
AU Zhao, P
AF Zhao, Ping
TI Strategies, techniques, applications of combining top-down and bottom-up
approaches in PBPK models
SO DRUG METABOLISM REVIEWS
LA English
DT Meeting Abstract
CT 20th North American Meeting of the
International-Society-for-the-Study-of-Xenobiotics (ISSX)
CY OCT 18-22, 2015
CL Orlando, FL
SP Int Soc Study Xenobiot
C1 [Zhao, Ping] US FDA, Off Clin Pharmacol, CDER, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0360-2532
EI 1097-9883
J9 DRUG METAB REV
JI Drug Metab. Rev.
PY 2016
VL 48
SU 1
MA SC1.1
BP 6
EP 6
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DS4IO
UT WOS:000380744900002
ER
PT J
AU Wang, YN
AF Wang, Yaning
TI Dose justification for special population: regulatory perspective
SO DRUG METABOLISM REVIEWS
LA English
DT Meeting Abstract
CT 20th North American Meeting of the
International-Society-for-the-Study-of-Xenobiotics (ISSX)
CY OCT 18-22, 2015
CL Orlando, FL
SP Int Soc Study Xenobiot
C1 [Wang, Yaning] US FDA, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0360-2532
EI 1097-9883
J9 DRUG METAB REV
JI Drug Metab. Rev.
PY 2016
VL 48
SU 1
MA SC2.3
BP 7
EP 7
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DS4IO
UT WOS:000380744900005
ER
PT J
AU Blank, M
AF Blank, Melanie
TI Renal biomarkers
SO DRUG METABOLISM REVIEWS
LA English
DT Meeting Abstract
CT 20th North American Meeting of the
International-Society-for-the-Study-of-Xenobiotics (ISSX)
CY OCT 18-22, 2015
CL Orlando, FL
SP Int Soc Study Xenobiot
C1 [Blank, Melanie] US FDA, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0360-2532
EI 1097-9883
J9 DRUG METAB REV
JI Drug Metab. Rev.
PY 2016
VL 48
SU 1
MA S21
BP 15
EP 15
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DS4IO
UT WOS:000380744900027
ER
PT J
AU Zhang, L
AF Zhang, Lei
TI A scientific perspective on drug interaction evaluation during drug
development
SO DRUG METABOLISM REVIEWS
LA English
DT Meeting Abstract
CT 20th North American Meeting of the
International-Society-for-the-Study-of-Xenobiotics (ISSX)
CY OCT 18-22, 2015
CL Orlando, FL
SP Int Soc Study Xenobiot
C1 [Zhang, Lei] US FDA, Off Clin Pharmacol, CDER, Silver Spring, MD USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0360-2532
EI 1097-9883
J9 DRUG METAB REV
JI Drug Metab. Rev.
PY 2016
VL 48
SU 1
MA S26
BP 16
EP 16
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DS4IO
UT WOS:000380744900031
ER
PT J
AU Sato, M
Liu, Q
Yoshida, K
Li, L
Rekic, D
Reynolds, K
Zhang, L
Huang, SM
Sinha, V
Zhao, P
AF Sato, Masanobu
Liu, Qi
Yoshida, Kenta
Li, Li
Rekic, Dinko
Reynolds, Kellie
Zhang, Lei
Huang, Shiew Mei
Sinha, Vikram
Zhao, Ping
TI Evaluation of drug interaction potential of CYP3A substrates - a
tailored approach based on FM,CYP3A
SO DRUG METABOLISM REVIEWS
LA English
DT Meeting Abstract
CT 20th North American Meeting of the
International-Society-for-the-Study-of-Xenobiotics (ISSX)
CY OCT 18-22, 2015
CL Orlando, FL
SP Int Soc Study Xenobiot
C1 [Sato, Masanobu; Liu, Qi; Yoshida, Kenta; Rekic, Dinko; Reynolds, Kellie; Zhang, Lei; Huang, Shiew Mei; Sinha, Vikram; Zhao, Ping] US FDA, Off Clin Pharmacol, CDER, Silver Spring, MD USA.
[Sato, Masanobu] Pharmaceut & Med Devices Agcy PMDA, Silver Spring, MD USA.
[Li, Li] CFDA, Ctr Drug Evaluat, Off Gener Drug Pharmaceut Sci, Beijing, Peoples R China.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0360-2532
EI 1097-9883
J9 DRUG METAB REV
JI Drug Metab. Rev.
PY 2016
VL 48
SU 1
MA P91
BP 70
EP 71
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DS4IO
UT WOS:000380744900147
ER
PT J
AU Volpe, DA
Avaritt, BR
AF Volpe, Donna A.
Avaritt, Brittany R.
TI Correlation of in vitro inhibition of midazolam CYP3A4-mediated
metabolism to in vivo drug interactions
SO DRUG METABOLISM REVIEWS
LA English
DT Meeting Abstract
CT 20th North American Meeting of the
International-Society-for-the-Study-of-Xenobiotics (ISSX)
CY OCT 18-22, 2015
CL Orlando, FL
SP Int Soc Study Xenobiot
C1 [Volpe, Donna A.; Avaritt, Brittany R.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0360-2532
EI 1097-9883
J9 DRUG METAB REV
JI Drug Metab. Rev.
PY 2016
VL 48
SU 1
MA P127
BP 88
EP 88
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DS4IO
UT WOS:000380744900181
ER
PT J
AU Myers, MB
AF Myers, Meagan B.
TI Targeted therapies with companion diagnostics in the management of
breast cancer: current perspectives
SO PHARMACOGENOMICS & PERSONALIZED MEDICINE
LA English
DT Review
DE HER2; precision medicine; in vitro diagnostics; estrogen receptor;
multigene assay
ID ADJUVANT ENDOCRINE THERAPY; PRACTICE GUIDELINE UPDATE; INTERNATIONAL
EXPERT CONSENSUS; 21-GENE RECURRENCE SCORE; LATE DISTANT RECURRENCE;
ESTROGEN-RECEPTOR; CLINICAL-PRACTICE; AMERICAN SOCIETY; GENE-EXPRESSION;
PAM50 RISK
AB Breast cancer is a multifaceted disease exhibiting both intertumoral and intratumoral heterogeneity as well as variable disease course. Over 2 decades of research has advanced the understanding of the molecular substructure of breast cancer, directing the development of new therapeutic strategies against these actionable targets. In vitro diagnostics, and specifically companion diagnostics, have been integral in the successful development and implementation of these targeted therapies, such as those directed against the human epidermal growth factor receptor 2. Lately, there has been a surge in the development, commercialization, and marketing of diagnostic assays to assist in breast cancer patient care. More recently, multigene signature assays, such as Oncotype DX, MammaPrint, and Prosigna, have been integrated in the clinical setting in order to tailor decisions on adjuvant endocrine and chemotherapy treatment. This review provides an overview of the current state of breast cancer management and the use of companion diagnostics to direct personalized approaches in the treatment of breast cancer.
C1 [Myers, Meagan B.] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
RP Myers, MB (reprint author), US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM meagan.myers@fda.hhs.gov
NR 78
TC 3
Z9 3
U1 0
U2 4
PU DOVE MEDICAL PRESS LTD
PI ALBANY
PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND
SN 1178-7066
J9 PHARMACOGN PERS MED
JI Pharmacogn. Pers. Med.
PY 2016
VL 9
BP 7
EP 16
DI 10.2147/PGPM.S56055
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DU0IL
UT WOS:000381886300002
PM 26858530
ER
PT S
AU Munos, B
Baker, PC
Bot, BM
Crouthamel, M
de Vries, G
Ferguson, I
Hixson, JD
Malek, LA
Mastrototaro, JJ
Misra, V
Ozcan, A
Sacks, L
Wang, P
AF Munos, Bernard
Baker, Pamela C.
Bot, Brian M.
Crouthamel, Michelle
de Vries, Glen
Ferguson, Ian
Hixson, John D.
Malek, Linda A.
Mastrototaro, John J.
Misra, Veena
Ozcan, Aydogan
Sacks, Leonard
Wang, Pei
GP Annals New York Acad Sci
TI Mobile health: the power of wearables, sensors, and apps to transform
clinical trials
SO SPECIAL ISSUE: ANNALS REPORTS, VOL 1375
SE Annals of the New York Academy of Sciences
LA English
DT Article; Book Chapter
DE biosensors; mobile technology; wireless; medical device; health care;
data; clinical study
ID ON-CHIP MICROSCOPY
AB Mobile technology has become a ubiquitous part of everyday life, and the practical utility of mobile devices for improving human health is only now being realized. Wireless medical sensors, or mobile biosensors, are one such technology that is allowing the accumulation of real-time biometric data that may hold valuable clues for treating even some of the most devastating human diseases. From wearable gadgets to sophisticated implantable medical devices, the information retrieved from mobile technology has the potential to revolutionize how clinical research is conducted and how disease therapies are delivered in the coming years. Encompassing the fields of science and engineering, analytics, health care, business, and government, this report explores the promise that wearable biosensors, along with integrated mobile apps, hold for improving the quality of patient care and clinical outcomes. The discussion focuses on groundbreaking device innovation, data optimization and validation, commercial platform integration, clinical implementation and regulation, and the broad societal implications of using mobile health technologies.
C1 [Munos, Bernard] Milken Inst, FasterCures, Washington, DC 20005 USA.
[Baker, Pamela C.] Questex Media Grp LLC, FierceBigData, Newton, MA USA.
[Bot, Brian M.] Sage Bionetworks, Seattle, WA USA.
[Crouthamel, Michelle] GlaxoSmithKline, Collegeville, PA USA.
[de Vries, Glen] Medidata Solut, New York, NY USA.
[Ferguson, Ian] ARM, San Francisco, CA USA.
[Hixson, John D.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Hixson, John D.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Malek, Linda A.] Moses & Singer LLP, Healthcare & Privacy & Cybersecur Practices, New York, NY USA.
[Mastrototaro, John J.] Medtronic PLC, Los Angeles, CA USA.
[Misra, Veena] North Carolina State Univ, NSF Nanosyst Engn Res Ctr NERC Adv Self Powered S, Raleigh, NC USA.
[Ozcan, Aydogan] Univ Calif Los Angeles, Calif NanoSyst Inst, Los Angeles, CA USA.
[Ozcan, Aydogan] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA USA.
[Ozcan, Aydogan] Univ Calif Los Angeles, Dept Elect Engn, Los Angeles, CA 90024 USA.
[Sacks, Leonard] US FDA, Silver Spring, MD USA.
[Wang, Pei] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
RP Munos, B (reprint author), Milken Inst, FasterCures, Washington, DC 20005 USA.
EM annals@nyas.org
RI Emchi, Karma/Q-1952-2016
NR 40
TC 1
Z9 1
U1 14
U2 14
PU BLACKWELL SCIENCE PUBL
PI OXFORD
PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND
SN 0077-8923
J9 ANN NY ACAD SCI
JI Ann.NY Acad.Sci.
PY 2016
VL 1375
BP 3
EP 18
DI 10.1111/nyas.13117
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA BF5HR
UT WOS:000382005200001
PM 27384501
ER
PT S
AU Bozza, WP
Twomey, JD
Kim, SR
Zhang, BL
AF Bozza, William P.
Twomey, Julianne D.
Kim, Su-Ryun
Zhang, Baolin
BE Muganda, PM
TI Detection of Apoptosis: From Bench Side to Clinical Practice
SO APOPTOSIS METHODS IN TOXICOLOGY
SE Methods in Pharmacology and Toxicology
LA English
DT Article; Book Chapter
DE Apoptosis; Apoptosis detection; In vitro apoptosis detection; In vivo
apoptosis detection; Clinical apoptosis detection; DNA fragmentation;
TUNEL; Caspase activation detection; Phosphatidylserine externalization
ID PROGRAMMED CELL-DEATH; FLUOROCHROME-LABELED INHIBITORS; RADIOLABELED
ANNEXIN-V; IN-VIVO EVALUATION; IMAGING CASPASE-3 ACTIVATION;
TC-99M-LABELED C2A DOMAIN; FLOW-CYTOMETRIC DETECTION; PROTON MR
SPECTROSCOPY; LARGE DNA-MOLECULES; PHOSPHATIDYLSERINE EXPRESSION
AB Apoptosis or programmed cell death is implicated in several pathological conditions, such as cancer and neurodegenerative diseases. An increasing number of therapies are developed by targeting apoptosis signaling components to either induce or inhibit apoptosis in target cells. For these reasons, it is critical to develop appropriate analytical methods for the detection of apoptotic cell death in the context of monitoring relevant disease progression and therapeutic effects of clinical treatments (e.g., chemotherapy in cancer patients). This review provides an overview of the currently used methods for detection of apoptosis and their applications in research and clinical practice.
C1 [Bozza, William P.; Twomey, Julianne D.; Kim, Su-Ryun; Zhang, Baolin] US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Bozza, WP (reprint author), US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
NR 124
TC 0
Z9 0
U1 3
U2 3
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1557-2153
BN 978-1-4939-3588-8; 978-1-4939-3586-4
J9 METHOD PHARMACOL TOX
JI Methods Pharmacol. Toxicol.
PY 2016
BP 13
EP 29
DI 10.1007/978-1-4939-3588-8_2
D2 10.1007/978-1-4939-3588-8
PG 17
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA BF4TD
UT WOS:000381683500003
ER
PT S
AU Seng, WL
Zhang, DW
McGrath, P
AF Seng, Wen Lin
Zhang, Dawei
McGrath, Patricia
BE Muganda, PM
TI Microplate-Based Whole Zebrafish Caspase 3/7 Assay for Screening Small
Molecule Compounds
SO APOPTOSIS METHODS IN TOXICOLOGY
SE Methods in Pharmacology and Toxicology
LA English
DT Article; Book Chapter
DE Acridine orange; Assay; Apoptosis; Caspase; Chemiluminescence; ELISA;
Methods; Microplate; Whole zebrafish
ID PHYLOGENETIC ANALYSIS; KINETIC-ANALYSIS; IN-VIVO; APOPTOSIS; INHIBITOR;
CELLS; SPECIFICITY; VALIDATION; INDUCTION
AB In this research, using a commercially available human specific caspase 3/7 chemiluminescent test kit (Caspase 3/7 Glo, Promega, Madison, WI), developed for cell based assays, we describe a microplate-based whole zebrafish assay format to identify potential small molecule caspase inhibitors and activators. Based on the high degree of evolutionary conservation among species, we show that human specific 3/7 substrate cross reacts with zebrafish. Using untreated zebrafish, optimum assay conditions (including substrate concentration, number of zebrafish per microwell, and incubation time to generate a linear reaction) are determined. Robustness and reproducibility of the assay are established using a characterized caspase 3/7 inhibitor (z-VAD-fmk) and an activator (staurosporine). Next, the whole zebrafish microplate assay format is validated using three additional characterized caspase 3/7 inhibitors, two additional caspase 3/7 activators, and one control compound that has no effect on zebrafish apoptosis. Compared to other whole animal assay formats, chemiluminescence provides high sensitivity and low background. Next, results are compared with published results in mammalian cell based assays and animal models and show that the overall predictive success rate is 100 %. Compound effects on apoptosis are further confirmed visually by whole mount staining with acridine orange (AO), a live dye. Results support the high degree of conservation of key pathways in zebrafish and humans. The microplate-based whole zebrafish caspase 3/7 assay format represents a rapid, reproducible, predictive animal model for identifying potential inhibitors and activators. Use of zebrafish as an alternative animal model to identify potential apoptosis modulators can accelerate the drug discovery process and reduce costs.
C1 [Seng, Wen Lin; McGrath, Patricia] Phylonix, Cambridge, MA 02139 USA.
[Zhang, Dawei] US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Seng, WL (reprint author), Phylonix, Cambridge, MA 02139 USA.
NR 33
TC 0
Z9 0
U1 1
U2 1
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1557-2153
BN 978-1-4939-3588-8; 978-1-4939-3586-4
J9 METHOD PHARMACOL TOX
JI Methods Pharmacol. Toxicol.
PY 2016
BP 193
EP 209
DI 10.1007/978-1-4939-3588-8_11
D2 10.1007/978-1-4939-3588-8
PG 17
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA BF4TD
UT WOS:000381683500012
ER
PT J
AU Li, XJ
Zhang, L
Zhou, RF
Yu, CY
Shi, CL
Shao, C
Li, Y
Xu, DQ
AF Li, Xiaojie
Zhang, Ling
Zhou, Ruifang
Yu, Chunyu
Shi, Chaoling
Shao, Chen
Li, Yang
Xu, Deqi
TI Effects of a human plasma membrane-associated sialidase siRNA on
prostate cancer
SO INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY
LA English
DT Article
DE Neu3; siRNA; tunnel; apoptosis; Attenuated Salmonella
ID PROTEIN EXPRESSION THERAPY; SALMONELLA-TYPHIMURIUM; APOPTOSIS
SUPPRESSION; TUMOR; VOLUNTEERS; VECTOR; NEU3
AB Human plasma membrane-associated sialidase (Neu3) mainly localized in plasma membranes and plays crucial roles in the regulation of cell surface functions. We investigated the effects and molecular mechanisms of Neu3 on cell growth and apoptosis in vivo and in vitro in this study. Initially, we found the levels of Neu3 expression were higher in prostate cancer tissues and cell lines than in normal prostate tissues. We then applied a Neu3 siRNA approach to block Neu3 signaling using PC-3M cells as model cells. PC-3M cells transfected with Neu3-specific short hairpin RNA plasmid inhibited cell proliferation and induced apoptosis significantly. Knocking down neu3 decreased the expression of Bcl-2 and increased the expression of Bax, Caspase-3 in PC-3M cells. The experiments suggest that Neu3 is a promising molecular target for prostate cancer therapy.
C1 [Li, Xiaojie; Zhou, Ruifang] Taizhou Polytech Coll, Taizhou, Peoples R China.
[Li, Xiaojie; Zhang, Ling; Yu, Chunyu; Shi, Chaoling; Shao, Chen; Li, Yang] Jilin Univ, Coll Basic Med Sci, Prostate Dis Prevent & Treatment Res Ctr, Dept Pathophysiol, Changchun, Peoples R China.
[Xu, Deqi] US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
RP Li, Y (reprint author), Jilin Univ, Norman Bethune Med Sch, Prostate Dis Prevent & Treatment Res Ctr, Dept Pathophysiol, Xinmin St, Changchun 130021, Peoples R China.
EM lyang@jlu.edu.cn
NR 18
TC 0
Z9 0
U1 1
U2 1
PU E-CENTURY PUBLISHING CORP
PI MADISON
PA 40 WHITE OAKS LN, MADISON, WI 53711 USA
SN 1936-2625
J9 INT J CLIN EXP PATHO
JI Int. J. Clin. Exp. Pathol.
PY 2016
VL 9
IS 3
BP 4101
EP 4109
PG 9
WC Oncology; Pathology
SC Oncology; Pathology
GA DO2FA
UT WOS:000377594100175
ER
PT J
AU Korang-Yeboah, M
Rahman, Z
Shah, DA
Khan, MA
AF Korang-Yeboah, Maxwell
Rahman, Ziyaur
Shah, Dhaval A.
Khan, Mansoor A.
TI Spectroscopic-Based Chemometric Models for Quantifying Low Levels of
Solid-State Transitions in Extended Release Theophylline Formulations
SO JOURNAL OF PHARMACEUTICAL SCIENCES
LA English
DT Article
DE chemometrics; controlled release; partial least squares; formulation;
near-infrared spectroscopy; Raman spectroscopy; pseudopolymorph; solid
state stability
ID PHARMACEUTICAL SOLIDS; REFLECTANCE SPECTRA; HYDRATE FORMATION;
DRUG-RELEASE; TABLETS; CRYSTALLIZATION; QUANTIFICATION; MOISTURE;
POWDER; RAMAN
AB Variations in the solid state form of a pharmaceutical solid have profound impact on the product quality and clinical performance. Quantitative models that allow rapid and accurate determination of polymorphic changes in pharmaceutical products are essential in ensuring product quality throughout its lifecycle. This study reports the development and validation of chemometric models of Raman and near infrared spectroscopy (NIR) for quantifying the extent of pseudopolymorphic transitions of theophylline in extended release formulations. The chemometric models were developed using sample matrices consisting of the commonly used excipients and at the ratios in commercially available products. A combination of scatter removal (multiplicative signal correction and standard normal variate) and derivatization (Savitzky-Golay second derivative) algorithm were used for data pretreatment. Partial least squares and principal component regression models were developed and their performance assessed. Diagnostic statistics such as the root mean square error, correlation coefficient, bias and Q(2) were used as parameters to test the model fit and performance. The models developed had a good fit and performance as shown by the values of the diagnostic statistics. The model diagnostic statistics were similar for MSC-SG and SNV-SG treated spectra. Similarly, PLSR and PCR models had comparable performance. Raman chemometric models were slightly better than their corresponding NIR model. The Raman and NIR chemometric models developed had good accuracy and precision as demonstrated by closeness of the predicted values for the independent observations to the actual TMO content hence the developed models can serve as useful tools in quantifying and controlling solid state transitions in extended release theophylline products. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
C1 [Korang-Yeboah, Maxwell; Rahman, Ziyaur; Shah, Dhaval A.] US FDA, Div Prod Qual & Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Khan, Mansoor A.] Texas A&M Hlth Sci Ctr, Irma Lerma Rangel Coll Pharm, College Stn, TX 77843 USA.
RP Khan, MA (reprint author), Texas A&M Hlth Sci Ctr, Irma Lerma Rangel Coll Pharm, College Stn, TX 77843 USA.
EM mkhan@pharmacy.tamhsc.edu
OI Rahman, Ziyaur/0000-0002-0402-825X
NR 32
TC 1
Z9 1
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3549
EI 1520-6017
J9 J PHARM SCI-US
JI J. Pharm. Sci.
PD JAN
PY 2016
VL 105
IS 1
BP 97
EP 105
DI 10.1016/j.xphs.2015.11.007
PG 9
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology &
Pharmacy
SC Pharmacology & Pharmacy; Chemistry
GA DT8TN
UT WOS:000381768000014
PM 26852844
ER
PT J
AU Moreno, FS
Heidor, R
Pogribny, IP
AF Moreno, Fernando Salvador
Heidor, Renato
Pogribny, Igor P.
TI Nutritional Epigenetics and the Prevention of Hepatocellular Carcinoma
with Bioactive Food Constituents
SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
LA English
DT Review
ID RAT-LIVER CARCINOGENESIS; ADENOSYL-L-METHIONINE; LONG NONCODING RNA;
NONALCOHOLIC FATTY LIVER; TUMOR-SUPPRESSOR GENE; PERICENTROMERIC
SATELLITE REGIONS; HISTONE LYSINE METHYLTRANSFERASE; CANCER
CHEMOPREVENTIVE AGENT; GLYCINE N-METHYLTRANSFERASE; DIETARY METHYL
DEFICIENCY
AB Hepatocellular carcinoma (HCC) is an aggressive and life-threatening disease often diagnosed at intermediate or advanced stages, which substantially limits therapeutic approaches to its successful treatment. This indicates that the prevention of HCC may be the most promising strategy in reducing its incidence and mortality. Emerging evidence indicates that numerous nutrients and nonnutrient dietary bioactive components can reduce the occurrence and/or delay the development of HCC through modifications of deregulated epigenetic mechanisms. This review examines the existing knowledge on the epigenetic mechanism-based studies in in vitro and in vivo models of HCC on the chemopreventive potential of epigenetic food components, including dietary methyl-group donors, epigallocatechin-3-gallate, sodium butyrate, resveratrol, curcumin, and sulforaphane, on liver carcinogenesis. Future direction and potential challenges in the effective use of bioactive food constituents in the prevention of HCC are highlighted and discussed.
C1 [Moreno, Fernando Salvador; Heidor, Renato] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Food & Expt Nutr, Lab Diet Nutr & Canc, Sao Paulo, Brazil.
[Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM igor.pogribny@fda.hhs.gov
RI Moreno, Fernando/I-1943-2013
FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [FAPESP]
[2013/20477-6]; Conselho Nacional de Desenvolvimento Cientifico e
Tecnologico [CNPq] [455663/2014-9]
FX Financial support was received from the Fundacao de Amparo a Pesquisa do
Estado de Sao Paulo [FAPESP] projeto 2013/20477-6 and Conselho Nacional
de Desenvolvimento Cientifico e Tecnologico [CNPq] projeto
455663/2014-9.
NR 198
TC 0
Z9 0
U1 2
U2 2
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 0163-5581
EI 1532-7914
J9 NUTR CANCER
JI Nutr. Cancer
PY 2016
VL 68
IS 5
BP 719
EP 733
DI 10.1080/01635581.2016.1180410
PG 15
WC Oncology; Nutrition & Dietetics
SC Oncology; Nutrition & Dietetics
GA DS6HP
UT WOS:000380883200001
PM 27266713
ER
PT J
AU Karunathilaka, SR
Farris, S
Mossoba, MM
Moore, JC
Yakes, BJ
AF Karunathilaka, Sanjeewa R.
Farris, Samantha
Mossoba, Magdi M.
Moore, Jeffrey C.
Yakes, Betsy Jean
TI Characterising variances of milk powder and instrumentation for the
development of a non-targeted, Raman spectroscopy and chemometrics
detection method for the evaluation of authenticity
SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL
EXPOSURE & RISK ASSESSMENT
LA English
DT Article
DE Skim milk powder (SMP); non-fat dry milk (NFDM); authentication; Raman
spectroscopy; chemometrics; PCA; variance
ID NEAR-INFRARED SPECTROSCOPY; ECONOMICALLY MOTIVATED ADULTERATION;
NUTRITIONAL PARAMETERS; OLIVE OIL; FT-RAMAN; SPECTRA; SKIM; MELAMINE;
LACTOSE
AB There is a need to develop rapid tools to screen milk products for economically motivated adulteration. An understanding of the physiochemical variability within skim milk powder (SMP) and non-fat dry milk (NFDM) is the key to establishing the natural differences of these commodities prior to the development of non-targeted detection methods. This study explored the sources of variance in 71 commercial SMP and NFDM samples using Raman spectroscopy and principal component analysis (PCA) and characterised the largest number of commercial milk powders acquired from a broad number of international manufacturers. Spectral pre-processing using a gap-segment derivative transformation (gap size = 5, segment width = 9, fourth derivative) in combination with sample normalisation was necessary to reduce the fluorescence background of the milk powder samples. PC scores plots revealed no clear trends for various parameters, including day of analysis, powder type, supplier and processing temperatures, while the largest variance was due to irreproducibility in sample positioning. Significant chemical sources of variances were explained by using the spectral features in the PC loadings plots where four samples from the same manufacturer were determined to likely contain an additional component or lactose anomers, and one additional sample was identified as an outlier and likely containing an adulterant or differing quality components. The variance study discussed herein with this large, diverse set of milk powders holds promise for future use as a non-targeted screening method that could be applied to commercial milk powders.
C1 [Karunathilaka, Sanjeewa R.; Farris, Samantha; Mossoba, Magdi M.; Yakes, Betsy Jean] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
[Moore, Jeffrey C.] US Pharmacopeial Convent Inc, Rockville, MD USA.
RP Yakes, BJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM Betsy.Yakes@fda.hhs.gov
FU Research Participation Program at the Center for Food Safety and the
Applied Nutrition
FX S.R.K. acknowledges the support provided by an appointment to the
Research Participation Program at the Center for Food Safety and the
Applied Nutrition, administered by the Oak Ridge Institute for Science
and Education through an interagency agreement between the US Department
of Energy and the US Food and Drug Administration (US FDA).
NR 38
TC 1
Z9 1
U1 4
U2 8
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1944-0049
EI 1944-0057
J9 FOOD ADDIT CONTAM A
JI Food Addit. Contam. Part A-Chem.
PY 2016
VL 33
IS 6
BP 921
EP 932
DI 10.1080/19440049.2016.1188437
PG 12
WC Chemistry, Applied; Food Science & Technology; Toxicology
SC Chemistry; Food Science & Technology; Toxicology
GA DR8GX
UT WOS:000380137500001
PM 27167451
ER
PT J
AU White, J
Wrzesinski, C
Green, M
Johnson, GT
McCluskey, JD
Abritis, A
Harbison, RD
AF White, Jennifer
Wrzesinski, Claudia
Green, Martin
Johnson, Giffe T.
McCluskey, James D.
Abritis, Alison
Harbison, Raymond D.
TI A novel method for deriving thresholds of toxicological concern for
vaccine constituents
SO TOXICOLOGY MECHANISMS AND METHODS
LA English
DT Article
DE Biologics; QSAR; TTCs; vaccine safety
AB Safety assessment evaluating the presence of impurities, residual materials, and contaminants in vaccines is a focus of current research. Thresholds of toxicological concern (TTCs) are mathematically modeled levels used for assessing the safety of many food and medication constituents. In this study, six algorithms are selected from the open-access ToxTree software program to derive a method for calculating TTCs for vaccine constituents: In Vivo Rodent Micronucleus assay/LD50, Benigni-Bossa/LD50, Cramer Extended/LD50, In Vivo Rodent Micronucleus assay/TDLo, Benigni-Bossa/TDLo, and the Cramer Extended/TDLo. Using an initial dataset (n = 197) taken from INCHEM, RepDose, RTECS, and TOXNET, the chemicals were divided into two families: "positive" - based on the presence of structures associated with adverse outcomes, or "negative" - no such structures or having structures that appear to be protective of health. The final validation indicated that the Benigni-Bossa/LD50 method is the most appropriate for calculating TTCs for vaccine constituents. Final TTCs were designated as 18.06 mu g/person and 20.61 mu g/person for the Benigni-Bossa/LD50 positive and negative structural families, respectively.
C1 [White, Jennifer; Johnson, Giffe T.; McCluskey, James D.; Abritis, Alison; Harbison, Raymond D.] Univ S Florida, Coll Publ Hlth, Ctr Environm & Occupat Risk Anal & Management, Tampa, FL 33612 USA.
[Wrzesinski, Claudia; Green, Martin] US FDA, Rockville, MD USA.
RP Harbison, RD (reprint author), Univ S Florida, Coll Publ Hlth, Ctr Environm & Occupat Risk Anal & Management, Tampa, FL 33612 USA.
EM rharbison@ix.netcom.com
NR 13
TC 1
Z9 1
U1 2
U2 2
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1537-6516
EI 1537-6524
J9 TOXICOL MECH METHOD
JI Toxicol. Mech. Methods
PY 2016
VL 26
IS 4
BP 270
EP 275
DI 10.3109/15376516.2016.1170250
PG 6
WC Toxicology
SC Toxicology
GA DR7AP
UT WOS:000380052700006
PM 27098016
ER
PT J
AU Alayash, AI
AF Alayash, Abdu I.
TI Memorial - Dr. Joseph C. Fratantoni
SO ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY
LA English
DT Biographical-Item
C1 [Alayash, Abdu I.] US FDA, Lab Biochem & Vasc Biol, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave Bldg 52-72,Room 4106, Silver Spring, MD 20993 USA.
RP Alayash, AI (reprint author), US FDA, Lab Biochem & Vasc Biol, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave Bldg 52-72,Room 4106, Silver Spring, MD 20993 USA.
EM abdu.alayash@fda.hhs.gov
NR 1
TC 0
Z9 0
U1 0
U2 1
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 2169-1401
EI 2169-141X
J9 ARTIF CELL NANOMED B
JI Artif. Cell. Nanomed. Biotechnol.
PY 2016
VL 44
IS 4
BP 1049
EP 1049
DI 10.3109/21691401.2016.1154278
PG 1
WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Materials
Science, Biomaterials
SC Biotechnology & Applied Microbiology; Engineering; Materials Science
GA DQ9PL
UT WOS:000379541700001
PM 26950293
ER
PT J
AU Doell, DL
Folmer, DE
Lee, HS
Butts, KM
Carberry, SE
AF Doell, Diana L.
Folmer, Daniel E.
Lee, Hyoung S.
Butts, Kyla M.
Carberry, Susan E.
TI Exposure estimate for FD&C colour additives for the US population
SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL
EXPOSURE & RISK ASSESSMENT
LA English
DT Article
DE Dietary exposure; food consumption; FD&C Blue No. 1; FD&C Blue No. 2;
FD&C Green No. 3; FD&C Red No. 3; FD&C Red No. 40; FD&C Yellow No. 5;
FD&C Yellow No. 6
ID ARTIFICIAL FOOD COLORS; POTENTIAL BEHAVIORAL-IMPLICATIONS; COMMONLY
CONSUMED BEVERAGES; USAGE PATTERN; CHILDREN; CONSUMPTION; INDIA; KUWAIT
AB Dietary exposures to the seven food, drug, and cosmetic (FD&C) colour additives that are approved for general use in food in the United States were estimated for the US population (aged 2 years and older), children (aged 2-5 years) and teenage boys (aged 13-18 years) based on analytical levels of the FD&C colour additives in foods. Approximately 600 foods were chosen for analysis, based on a survey of product labels, for the levels of FD&C colour additives. Dietary exposure was estimated using both 2-day food consumption data from the combined 2007-10 National Health and Nutrition Examination Survey (NHANES) and 10-14-day food consumption data from the 2007-10 NPD Group, Inc. National Eating Trends - Nutrient Intake Database (NPD NET-NID). Dietary exposure was estimated at the mean and 90th percentile using three different exposure scenarios: low exposure, average exposure and high exposure, to account for the range in the amount of each FD&C colour additive for a given food. For all populations and all exposure scenarios, the highest cumulative eaters-only exposures in food were determined for FD&C Red No. 40, FD&C Yellow No. 5 and FD&C Yellow No. 6. In addition, the eaters-only exposure was estimated for individual food categories in order to determine which food categories contributed the most to the exposure for each FD&C colour additive. Breakfast Cereal, Juice Drinks, Soft Drinks, and Frozen Dairy Desserts/Sherbet (also referred to as Ice Cream, Frozen Yogurt, Sherbet (including Bars, Sticks, Sandwiches)) were the major contributing food categories to exposure for multiple FD&C colour additives for all three populations.
C1 [Doell, Diana L.; Folmer, Daniel E.; Lee, Hyoung S.; Butts, Kyla M.; Carberry, Susan E.] US FDA, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, HFS 265,5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
RP Doell, DL (reprint author), US FDA, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, HFS 265,5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM Diana.Doell@fda.hhs.gov
FU Intramural FDA HHS [FD999999]
NR 28
TC 1
Z9 1
U1 7
U2 8
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1944-0049
EI 1944-0057
J9 FOOD ADDIT CONTAM A
JI Food Addit. Contam. Part A-Chem.
PY 2016
VL 33
IS 5
BP 782
EP 797
DI 10.1080/19440049.2016.1179536
PG 16
WC Chemistry, Applied; Food Science & Technology; Toxicology
SC Chemistry; Food Science & Technology; Toxicology
GA DR0KJ
UT WOS:000379596100005
PM 27092991
ER
PT J
AU Paseiro-Cerrato, R
Tongchat, C
Franz, R
AF Paseiro-Cerrato, Rafael
Tongchat, Chinawat
Franz, Roland
TI Study of the partition coefficients K-p/f of seven model migrants from
LDPE polymer in contact with food simulants
SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL
EXPOSURE & RISK ASSESSMENT
LA English
DT Article
DE Food-contact materials; low-density polyethylene (LDPE); migration
modelling; partition coefficients; temperature; food simulants
ID PACKAGING MATERIALS; TIME-TEMPERATURE; MIGRATION; FOODSTUFFS; PLASTICS;
ADDITIVES; PRODUCTS; KINETICS; SUPPORT; FILMS
AB This study evaluated the influence of parameters such as temperature and type of low-density polyethylene (LDPE) film on the log K-p/f values of seven model migrants in food simulants. Two different types of LDPE films contaminated by extrusion and immersion were placed in contact with three food simulants including 20% ethanol, 50% ethanol and olive oil under several time-temperature conditions. Results suggest that most log K-p/f values are little affected by these parameters in this study. In addition, the relation between log K-p/f and log P-o/w was established for each food simulant and regression lines, as well as correlation coefficients, were calculated. Correlations were compared with data from real foodstuffs. Data presented in this study could be valuable in assigning certain foods to particular food simulants as well as predicting the mass transfer of potential migrants into different types of food or food simulants, avoiding tedious and expensive laboratory analysis. The results could be especially useful for regulatory agencies as well as for the food industry.
C1 [Paseiro-Cerrato, Rafael] Univ Santiago de Compostela, Fac Pharm, Dept Analyt Chem Nutr & Food Sci, Santiago De Compostela, Spain.
[Tongchat, Chinawat; Franz, Roland] Fraunhofer Inst Proc Engn & Packaging IVV, Freising Weihenstephan, Germany.
[Paseiro-Cerrato, Rafael] USFDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
[Tongchat, Chinawat] Ctr ASEAN Food Contact Mat Testing, Dept Sci Serv, Bangkok 10400, Thailand.
RP Paseiro-Cerrato, R (reprint author), Univ Santiago de Compostela, Fac Pharm, Dept Analyt Chem Nutr & Food Sci, Santiago De Compostela, Spain.; Paseiro-Cerrato, R (reprint author), USFDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM Rafael.Cerrato@fda.hhs.gov
FU Ministerio de Ciencia e Innovacion [BES-2009-023016]
FX The authors are grateful to the Ministerio de Ciencia e Innovacion for a
Predoctoral Fellowship FPI [reference BES-2009-023016] awarded to Rafael
Paseiro-Cerrato.
NR 16
TC 0
Z9 0
U1 7
U2 8
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1944-0049
EI 1944-0057
J9 FOOD ADDIT CONTAM A
JI Food Addit. Contam. Part A-Chem.
PY 2016
VL 33
IS 5
BP 885
EP 892
DI 10.1080/19440049.2016.1166873
PG 8
WC Chemistry, Applied; Food Science & Technology; Toxicology
SC Chemistry; Food Science & Technology; Toxicology
GA DR0KJ
UT WOS:000379596100015
PM 26998811
ER
PT J
AU Ntim, SA
Thomas, TA
Noonan, GO
AF Ntim, Susana Addo
Thomas, Treye A.
Noonan, Gregory O.
TI Influence of aqueous food simulants on potential nanoparticle detection
in migration studies involving nanoenabled food-contact substances
SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL
EXPOSURE & RISK ASSESSMENT
LA English
DT Article
DE Silver nanoparticles; food simulant; stability; AF4; sp-ICP-MS
ID PLASMA-MASS SPECTROMETRY; SILVER NANOPARTICLES; CONTAINERS; NANOSILVER;
SIZE; PH; NANOCOMPOSITE; DISSOLUTION; SEPARATION; KINETICS
AB Research focused on assessing potential consumer exposure to nanoparticles released from nano-enabled food-contact materials (FCMs) has often reached conflicting conclusions regarding the detection of migrating nanoparticles. These conflicting conclusions, coupled with the potential for nanoparticles to be unstable in certain food simulants, has necessitated a closer look at the role played by food simulants recommended for use in nanoparticle migration evaluation. The influence of aqueous food simulants on nanoparticles under migration evaluation conditions is reported herein. The stability of silver nanoparticles (AgNP) spiked into three food simulants (water, 10% ethanol and 3% acetic acid) was investigated using asymmetric flow field-flow fractionation (AF4), ultrafiltration, electron microscopy (EM), and single-particle inductively coupled plasma mass spectrometry (sp-ICP-MS). While 3% acetic acid induced significant oxidative dissolution of AgNP to silver ions, there were very minor to no changes in the physicochemical properties of AgNP in water and 10% ethanol.
C1 [Ntim, Susana Addo; Noonan, Gregory O.] USFDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
[Thomas, Treye A.] US Consumer Prod Safety Commiss, Off Hazard Identificat & Reduct, Bethesda, MD USA.
RP Ntim, SA (reprint author), USFDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM susana.addontim@fda.hhs.gov
FU Center for Food Safety and Applied Nutrition
FX This project was supported in part by an appointment to the Research
Participation Program at the Center for Food Safety and Applied
Nutrition administered by the Oak Ridge Institute for Science and
Education through an interagency agreement between the US Consumer
Product Safety Commission (CPSC) and the US Food and Drug Administration
(USFDA).
NR 27
TC 1
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U1 4
U2 10
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1944-0049
EI 1944-0057
J9 FOOD ADDIT CONTAM A
JI Food Addit. Contam. Part A-Chem.
PY 2016
VL 33
IS 5
BP 905
EP 912
DI 10.1080/19440049.2016.1174506
PG 8
WC Chemistry, Applied; Food Science & Technology; Toxicology
SC Chemistry; Food Science & Technology; Toxicology
GA DR0KJ
UT WOS:000379596100017
ER
PT J
AU Guo, XQ
Mei, N
AF Guo, Xiaoqing
Mei, Nan
TI Aloe vera: A review of toxicity and adverse clinical effects
SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL
CARCINOGENESIS & ECOTOXICOLOGY REVIEWS
LA English
DT Review
DE Aloe gel; aloe latex; Aloe vera; carcinogenicity; genotoxicity;
toxicological effects
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; VAR. NATALENSIS BERGER; INNER LEAF
FILLET; BARBADENSIS MILLER; IN-VITRO; PHENOLIC-COMPOUNDS; SAFETY
EVALUATION; TOPOISOMERASE-II; MAMMALIAN-CELLS; HERBAL PRODUCTS
AB The Aloe plant is employed as a dietary supplement in a variety of foods and as an ingredient in cosmetic products. The widespread human exposure and its potential toxic and carcinogenic activities raise safety concerns. Chemical analysis reveals that the Aloe plant contains various polysaccharides and phenolic chemicals, notably anthraquinones. Ingestion of Aloe preparations is associated with diarrhea, hypokalemia, pseudomelanosis coli, kidney failure, as well as phototoxicity and hypersensitive reactions. Recently, Aloe vera whole leaf extract showed clear evidence of carcinogenic activity in rats, and was classified by the International Agency for Research on Cancer as a possible human carcinogen (Group 2B). This review presents updated information on the toxicological effects, including the cytotoxicity, genotoxicity, carcinogenicity, and adverse clinical effects of Aloe vera whole leaf extract, gel, and latex.
C1 [Guo, Xiaoqing; Mei, Nan] Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA.
RP Mei, N (reprint author), Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM Nan.Mei@fda.hhs.gov
NR 99
TC 2
Z9 3
U1 12
U2 16
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1059-0501
EI 1532-4095
J9 J ENVIRON SCI HEAL C
JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev.
PY 2016
VL 34
IS 2
BP 77
EP 96
DI 10.1080/10590501.2016.1166826
PG 20
WC Oncology; Environmental Sciences; Toxicology
SC Oncology; Environmental Sciences & Ecology; Toxicology
GA DR0RL
UT WOS:000379614500001
PM 26986231
ER
PT J
AU Rahman, MA
Lin, KK
Tiwari, RC
Jackson, M
AF Rahman, Mohammad A.
Lin, Karl K.
Tiwari, Ram C.
Jackson, Matthew
TI Exact Poly-K Test
SO COMMUNICATIONS IN STATISTICS-SIMULATION AND COMPUTATION
LA English
DT Article; Proceedings Paper
CT 1st Meeting of y-BIS / 1st Meeting of jSPE
CY JUL 23-26, 2012
CL Caparica, PORTUGAL
DE Carcinogenicity studies; Dose response; Exact test; Poly-K test
ID CARCINOGENICITY
AB For animal carcinogenicity study with multiple dose groups, positive trend test and pairwise comparisons of treated groups with control are generally performed using the Cochran-Armitage, Peto test, or Poly-K test. These tests are asymptotically normal. The exact version of Cochran-Armitage and Peto tests are available based on the permutation test assuming fixed column and row totals. For Poly-K test column totals depend on the mortality pattern of the animals and can not be kept fixed over the permutations of the animals. In this work a modification of the permutation test is suggested that can be applied on exact Poly-K test.
C1 [Rahman, Mohammad A.; Lin, Karl K.; Jackson, Matthew] US FDA, Div Biometr 6, Off Biostat, CDER, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
[Tiwari, Ram C.] US FDA, Off Biostat, CDER, Silver Spring, MD 20993 USA.
RP Rahman, MA (reprint author), US FDA, Div Biometr 6, Off Biostat, CDER, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM mohammad.rahman@fda.hhs.gov
NR 6
TC 0
Z9 0
U1 1
U2 1
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0361-0918
EI 1532-4141
J9 COMMUN STAT-SIMUL C
JI Commun. Stat.-Simul. Comput.
PY 2016
VL 45
IS 7
BP 2257
EP 2266
DI 10.1080/03610918.2014.901351
PG 10
WC Statistics & Probability
SC Mathematics
GA DQ2PK
UT WOS:000379044600003
ER
PT J
AU Austin, CA
Hinkley, GK
Mishra, AR
Zhang, Q
Umbreit, TH
Betz, MW
Wildt, BE
Casey, BJ
Francke-Carroll, S
Hussain, SM
Roberts, SM
Brown, KM
Goering, PL
AF Austin, Carlye A.
Hinkley, Georgia K.
Mishra, Anurag R.
Zhang, Qin
Umbreit, Thomas H.
Betz, Martha W.
Wildt, Bridget E.
Casey, Brendan J.
Francke-Carroll, Sabine
Hussain, Saber M.
Roberts, Stephen M.
Brown, Ken M.
Goering, Peter L.
TI Distribution and accumulation of 10 nm silver nanoparticles in maternal
tissues and visceral yolk sac of pregnant mice, and a potential effect
on embryo growth
SO NANOTOXICOLOGY
LA English
DT Article
DE Development; fetus; nanoparticles; nanosilver; pregnancy; toxicity
ID ORAL-EXPOSURE; PLACENTA; TOXICITY; TRANSFERRIN; TRANSPORT; STORAGE;
IONS; RATS
AB We examined the distribution of silver in pregnant mice and embryos/fetuses following intravenous injections of 10 nm silver nanoparticles (AgNPs) or soluble silver nitrate (AgNO3) at dose levels of 0 (citrate buffer control) or 66 mg Ag/mouse to pregnant mice on gestation days (GDs) 7, 8 and 9. Selected maternal tissues and all embryos/fetuses from control, AgNP- and AgNO3-treated groups on GD10 and control and AgNP-treated groups on GD16 were processed for the measurement of silver concentrations, intracellular AgNP localization, histopathology and gross examination of tissue morphology. Inductively-coupled plasma mass spectrometry revealed silver in all examined tissues following either AgNP or AgNO3 treatment, with highest concentrations of silver in maternal liver, spleen and visceral yolk sac (VYS), and lowest concentrations in embryos/fetuses. For VYS, mean silver concentration following AgNO3 treatment (4.87 ng Ag/mg tissue) was approximately two-fold that following AgNP treatment (2.31 ng Ag/mg tissue); for all other tissues examined, mean silver concentrations following either AgNP or AgNO3 treatment were not significantly different from each other (e.g. 2.57 or 2.84 ng Ag/mg tissue in maternal liver and 1.61 or 2.50 ng Ag/mg tissue in maternal spleen following AgNP or AgNO3 treatment, respectively). Hyperspectral imaging revealed AgNP aggregates in maternal liver, kidney, spleen and VYS from AgNP-treated mice, but not AgNO3-treated mice. Additionally, one or more embryos collected on GD10 from eight of ten AgNP-treated mice appeared small for their age (i.e. Theiler stage 13 [GD8.5] or younger). In the control group (N = 11), this effect was seen in embryos from only one mouse. In conclusion, intravenous injection of 10 nm AgNPs to pregnant mice resulted in notable silver accumulation in maternal liver, spleen and VYS, and may have affected embryonic growth. Silver accumulation in embryos/fetuses was negligible.
C1 [Austin, Carlye A.; Brown, Ken M.] George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA.
[Hinkley, Georgia K.; Roberts, Stephen M.] Univ Florida, Ctr Environm & Human Toxicol, Gainesville, FL USA.
[Mishra, Anurag R.; Zhang, Qin; Umbreit, Thomas H.; Betz, Martha W.; Wildt, Bridget E.; Casey, Brendan J.; Goering, Peter L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Francke-Carroll, Sabine] US FDA, Ctr Food Safety & Nutr, College Pk, MD USA.
[Hussain, Saber M.] Air Force Res Lab, Dayton, OH USA.
RP Goering, PL (reprint author), US FDA, Ctr Devices & Radiol Hlth, White Oak Life Sci Lab, WO64-4064,10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM peter.goering@fda.hhs.gov
NR 31
TC 1
Z9 1
U1 2
U2 10
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1743-5390
EI 1743-5404
J9 NANOTOXICOLOGY
JI Nanotoxicology
PY 2016
VL 10
IS 6
BP 654
EP 661
DI 10.3109/17435390.2015.1107143
PG 8
WC Nanoscience & Nanotechnology; Toxicology
SC Science & Technology - Other Topics; Toxicology
GA DQ5MA
UT WOS:000379248300002
PM 26593872
ER
PT J
AU Wildt, BE
Celedon, A
Maurer, EI
Casey, BJ
Nagy, AM
Hussain, SM
Goering, PL
AF Wildt, Bridget E.
Celedon, Alfredo
Maurer, Elizabeth I.
Casey, Brendan J.
Nagy, Amber M.
Hussain, Saber M.
Goering, Peter L.
TI Intracellular accumulation and dissolution of silver nanoparticles in
L-929 fibroblast cells using live cell time-lapse microscopy
SO NANOTOXICOLOGY
LA English
DT Article
DE Cellular uptake; confocal microscopy; ICP-MS; image analysis;
nanosilver; transmission electron microscopy; silver ions; silver
nanoparticles
ID IN-VITRO; ORAL-EXPOSURE; CYTOTOXICITY; TOXICITY; RESPONSES;
GENOTOXICITY; INFLAMMATION; BURNS; RATS
AB Cytotoxicity assessments of nanomaterials, such as silver nanoparticles, are challenging due to interferences with test reagents and indicators as well uncertainties in dosing as a result of the complex nature of nanoparticle intracellular accumulation. Furthermore, current theories suggest that silver nanoparticle cytotoxicity is a result of silver nanoparticle dissolution and subsequent ion release. This study introduces a novel technique, nanoparticle associated cytotoxicity microscopy analysis (NACMA), which combines fluorescence microscopy detection using ethidium homodimer-1, a cell permeability marker that binds to DNA after a cell membrane is compromised (a classical dead-cell indicator dye), with live cell time-lapse microscopy and image analysis to simultaneously investigate silver nanoparticle accumulation and cytotoxicity in L-929 fibroblast cells. Results of this method are consistent with traditional methods of assessing cytotoxicity and nanoparticle accumulation. Studies conducted on 10, 50, 100 and 200nm silver nanoparticles reveal size dependent cytotoxicity with particularly high cytotoxicity from 10nm particles. In addition, NACMA results, when combined with transmission electron microscopy imaging, reveal direct evidence of intracellular silver ion dissolution and possible nanoparticle reformation within cells for all silver nanoparticle sizes.
C1 [Wildt, Bridget E.; Casey, Brendan J.; Nagy, Amber M.; Goering, Peter L.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Celedon, Alfredo] Pontificia Univ Catolica Chile, Santiago, Chile.
[Celedon, Alfredo] Scanogen Inc, Baltimore, MD USA.
[Maurer, Elizabeth I.; Hussain, Saber M.] 711th Human Performance Wing, Appl Biotechnol Branch, Dayton, OH USA.
RP Goering, PL (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 64,Rm 4064, Silver Spring, MD 20993 USA.
EM peter.goering@fda.hhs.gov
FU U.S. Food and Drug Administration nanotechnology research funds
FX This work was supported by U.S. Food and Drug Administration
nanotechnology research funds. We acknowledge the Research Fellowship
Program support administered by the Oak Ridge Associated University
through a contract with the U.S. Food and Drug Administration.
NR 38
TC 0
Z9 0
U1 9
U2 21
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1743-5390
EI 1743-5404
J9 NANOTOXICOLOGY
JI Nanotoxicology
PY 2016
VL 10
IS 6
BP 710
EP 719
DI 10.3109/17435390.2015.1113321
PG 10
WC Nanoscience & Nanotechnology; Toxicology
SC Science & Technology - Other Topics; Toxicology
GA DQ5MA
UT WOS:000379248300008
PM 26643278
ER
PT J
AU Grabias, B
Kumar, S
AF Grabias, Bryan
Kumar, Sanjai
TI Adverse neuropsychiatric effects of antimalarial drugs
SO EXPERT OPINION ON DRUG SAFETY
LA English
DT Review
DE Antimalarials; neurotoxicity; psychiatric adverse events
ID PLASMODIUM-FALCIPARUM MALARIA; SUB-SAHARAN AFRICA; PROGRESSIVE
MULTIFOCAL LEUKOENCEPHALOPATHY; RANDOMIZED CONTROLLED-TRIAL;
DOUBLE-BLIND; ATOVAQUONE-PROGUANIL; DOXYCYCLINE PROPHYLAXIS; CHLOROQUINE
RESISTANCE; ARTEMISININ RESISTANCE; MEFLOQUINE TREATMENT
AB Introduction: Antimalarial drugs are the primary weapon to treat parasite infection, save lives, and curtail further transmission. Accumulating data have indicated that at least some antimalarial drugs may contribute to severe neurological and/or psychiatric side effects which further complicates their use and limits the pool of available medications.
Areas covered: In this review article, we summarize published scientific studies in search of evidence of the neuropsychiatric effects that may be attributed to the commonly used antimalarial drugs administered alone or in combination. Each individual drug was used as a search term in addition to keywords such as neuropsychiatric, adverse events, and neurotoxicity.
Expert opinion: Accumulating data based on published reports over several decades have suggested that among the major commonly used antimalarial drugs, only mefloquine exhibited clear indications of serious neurological and/or psychiatric side effects. A more systematic approach to assess the neuropsychiatric adverse effects of new or repurposed antimalarial drugs on their safety, tolerability and efficacy phases of clinical studies and in post-marketing surveillance, is needed to ensure that these life-saving tools remain available and can be prescribed with appropriate caution and medical judgment.
C1 [Grabias, Bryan; Kumar, Sanjai] US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
RP Kumar, S (reprint author), US FDA, Lab Emerging Pathogens, Dept Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, 10903 New Hampshire,Ave Bldg 52-72 Rm 5304, Silver Spring, MD 20993 USA.
EM Sanjai.Kumar@fda.hhs.gov
NR 104
TC 2
Z9 2
U1 7
U2 9
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1474-0338
EI 1744-764X
J9 EXPERT OPIN DRUG SAF
JI Expert Opin. Drug Saf.
PY 2016
VL 15
IS 7
BP 903
EP 910
DI 10.1080/14740338.2016.1175428
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DP9XA
UT WOS:000378850000004
PM 27077782
ER
PT J
AU Huang, L
Tang, L
Zhang, B
Zhang, ZW
Zhang, H
AF Huang, Lu
Tang, Li
Zhang, Bo
Zhang, Zhiwei
Zhang, Hui
TI Comparison of different computational implementations on fitting
generalized linear mixed-effects models for repeated count measures
SO JOURNAL OF STATISTICAL COMPUTATION AND SIMULATION
LA English
DT Article
DE Repeated count data; overdispersion; integral approximation;
linearization; R; SAS
ID ALGORITHMS; INFERENCE
AB In modelling repeated count outcomes, generalized linear mixed-effects models are commonly used to account for within-cluster correlations. However, inconsistent results are frequently generated by various statistical R packages and SAS procedures, especially in case of a moderate or strong within-cluster correlation or overdispersion. We investigated the underlying numerical approaches and statistical theories on which these packages and procedures are built. We then compared the performance of these statistical packages and procedures by simulating both Poisson-distributed and overdispersed count data. The SAS NLMIXED procedure outperformed the others procedures in all settings.
C1 [Huang, Lu; Tang, Li; Zhang, Hui] St Jude Childrens Res Hosp, Dept Biostat, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Zhang, Bo; Zhang, Zhiwei] US FDA, Div Biostat, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Zhang, H (reprint author), St Jude Childrens Res Hosp, Dept Biostat, 332 N Lauderdale St, Memphis, TN 38105 USA.
EM hui.zhang@stjude.org
RI Zhang, Hui/E-8112-2010
FU ALSAC
FX LH, LT, and HZ receive support from the ALSAC.
NR 31
TC 1
Z9 1
U1 0
U2 1
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0094-9655
EI 1563-5163
J9 J STAT COMPUT SIM
JI J. Stat. Comput. Simul.
PY 2016
VL 86
IS 12
BP 2392
EP 2404
DI 10.1080/00949655.2015.1111376
PG 13
WC Computer Science, Interdisciplinary Applications; Statistics &
Probability
SC Computer Science; Mathematics
GA DP7ZM
UT WOS:000378717700008
ER
PT S
AU Abbey, CK
Wu, YR
Burnside, ES
Wunderlich, A
Samuelson, FW
Boone, JM
AF Abbey, Craig K.
Wu, Yirong
Burnside, Elizabeth S.
Wunderlich, Adam
Samuelson, Frank W.
Boone, John M.
BE Abbey, CK
Kupinski, MA
TI A Utility/Cost Analysis of Breast Cancer Risk Prediction Algorithms
SO MEDICAL IMAGING 2016: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND
TECHNOLOGY ASSESSMENT
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Medical Imaging - Image Perception, Observer Performance,
and Technology Assessment
CY MAR 02-03, 2016
CL San Diego, CA
SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD
DE Risk prediction; breast cancer screening; expected cost; diagnostic
utility
ID SCREENING MAMMOGRAPHY; RELATIVE UTILITY; PERFORMANCE; RADIOLOGISTS;
WOMEN
AB Breast cancer risk prediction algorithms are used to identify subpopulations that are at increased risk for developing breast cancer. They can be based on many different sources of data such as demographics, relatives with cancer, gene expression, and various phenotypic features such as breast density. Women who are identified as high risk may undergo a more extensive (and expensive) screening process that includes MRI or ultrasound imaging in addition to the standard full-field digital mammography (FFDM) exam.
Given that there are many ways that risk prediction may be accomplished, it is of interest to evaluate them in terms of expected cost, which includes the costs of diagnostic outcomes. In this work we perform an expected-cost analysis of risk prediction algorithms that is based on a published model that includes the costs associated with diagnostic outcomes (true-positive, false-positive, etc.).
We assume the existence of a standard screening method and an enhanced screening method with higher scan cost, higher sensitivity, and lower specificity. We then assess expected cost of using a risk prediction algorithm to determine who gets the enhanced screening method under the strong assumption that risk and diagnostic performance are independent.
We find that if risk prediction leads to a high enough positive predictive value, it will be cost-effective regardless of the size of the subpopulation. Furthermore, in terms of the hit-rate and false-alarm rate of the of the risk-prediction algorithm, iso-cost contours are lines with slope determined by properties of the available diagnostic systems for screening.
C1 [Abbey, Craig K.] Univ Calif Santa Barbara, Dept Psychol & Brain Sci, Santa Barbara, CA 93106 USA.
[Wu, Yirong; Burnside, Elizabeth S.] Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA.
[Wunderlich, Adam; Samuelson, Frank W.] US FDA, Div Imaging & Appl Math, OSEL, CDRH, Silver Spring, MD 20993 USA.
[Boone, John M.] Univ Calif Davis, Med Ctr, Dept Radiol, Sacramento, CA 95817 USA.
RP Abbey, CK (reprint author), Univ Calif Santa Barbara, Dept Psychol & Brain Sci, Santa Barbara, CA 93106 USA.
NR 20
TC 0
Z9 0
U1 0
U2 0
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-5106-0022-5
J9 PROC SPIE
PY 2016
VL 9787
AR 97871J
DI 10.1117/12.2217850
PG 7
WC Optics; Radiology, Nuclear Medicine & Medical Imaging
SC Optics; Radiology, Nuclear Medicine & Medical Imaging
GA BF0CK
UT WOS:000378534200053
ER
PT S
AU Chen, WJ
Hu, N
AF Chen, Weijie
Hu, Nan
BE Abbey, CK
Kupinski, MA
TI Proper bibeta ROC model: algorithm, software, and performance evaluation
SO MEDICAL IMAGING 2016: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND
TECHNOLOGY ASSESSMENT
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Medical Imaging - Image Perception, Observer Performance,
and Technology Assessment
CY MAR 02-03, 2016
CL San Diego, CA
SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD
DE Proper ROC model; ROC curve fitting; maximum likelihood estimation; ROC
software
ID MAXIMUM-LIKELIHOOD-ESTIMATION; CURVES
AB Semi-parametric models are often used to fit data collected in receiver operating characteristic (ROC) experiments to obtain a smooth ROC curve and ROC parameters for statistical inference purposes. The proper bibeta model as recently proposed by Mossman and Peng enjoys several theoretical properties. In addition to having explicit density functions for the latent decision variable and an explicit functional form of the ROC curve, the two-parameter bibeta model also has simple closed-form expressions for true-positive fraction (TPF), false-positive fraction (FPF), and the area under the ROC curve (AUC). In this work, we developed a computational algorithm and R package implementing this model for ROC curve fitting. Our algorithm can deal with any ordinal data (categorical or continuous). To improve accuracy, efficiency, and reliability of our software, we adopted several strategies in our computational algorithm including: (1) the LABROC4 categorization to obtain the true maximum likelihood estimation of the ROC parameters; (2) a principled approach to initializing parameters; (3) analytical first-order and second-order derivatives of the likelihood function; (4) an efficient optimization procedure (the L-BFGS algorithm in the R package "nlopt"); and (5) an analytical delta method to estimate the variance of the AUC. We evaluated the performance of our software with intensive simulation studies and compared with the conventional binormal and the proper binormal-likelihood-ratio models developed at the University of Chicago. Our simulation results indicate that our software is highly accurate, efficient, and reliable.
C1 [Chen, Weijie] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Hu, Nan] Univ Iowa, Dept Math, Iowa City, IA 52242 USA.
RP Chen, WJ (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
EM weijie.chen@fda.hhs.gov
NR 16
TC 0
Z9 0
U1 0
U2 0
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-5106-0022-5
J9 PROC SPIE
PY 2016
VL 9787
AR 97870E
DI 10.1117/12.2216777
PG 8
WC Optics; Radiology, Nuclear Medicine & Medical Imaging
SC Optics; Radiology, Nuclear Medicine & Medical Imaging
GA BF0CK
UT WOS:000378534200013
ER
PT S
AU Han, M
Park, S
Baek, J
AF Han, Minah
Park, Subok
Baek, Jongduk
BE Abbey, CK
Kupinski, MA
TI Effect of anatomical backgrounds on detectability in volumetric cone
beam CT images
SO MEDICAL IMAGING 2016: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND
TECHNOLOGY ASSESSMENT
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Medical Imaging - Image Perception, Observer Performance,
and Technology Assessment
CY MAR 02-03, 2016
CL San Diego, CA
SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD
ID OBSERVER; CHANNELS; NOISE
AB As anatomical noise is often a dominating factor affecting signal detection in medical imaging, we investigate the effects of anatomical backgrounds on signal detection in volumetric cone beam CT images. Signal detection performances are compared between transverse and longitudinal planes with either uniform or anatomical backgrounds. Sphere objects with diameters of 1mm, 5mm, 8mm, and 11mm are used as the signals. Three-dimensional (3D) anatomical backgrounds are generated using an anatomical noise power spectrum, 1/f(beta), with beta=3, equivalent to mammographic background [1]. The mean voxel value of the 3D anatomical backgrounds is used as an attenuation coefficient of the uniform background. Noisy projection data are acquired by the forward projection of the uniform and anatomical 3D backgrounds with/without sphere lesions and by the addition of quantum noise. Then, images are reconstructed by an FDK algorithm [2]. For each signal size, signal detection performances in transverse and longitudinal planes are measured by calculating the task SNR of a channelized Hotelling observer with Laguerre-Gauss channels. In the uniform background case, transverse planes yield higher task SNR values for all sphere diameters but 1mm. In the anatomical background case, longitudinal planes yield higher task SNR values for all signal diameters. The results indicate that it is beneficial to use longitudinal planes to detect spherical signals in anatomical backgrounds.
C1 [Han, Minah; Baek, Jongduk] Yonsei Univ, Sch Integrated Technol, Seoul 120749, South Korea.
[Han, Minah; Baek, Jongduk] Yonsei Univ, Yonsei Inst Convergence Technol, Seoul 120749, South Korea.
[Park, Subok] US FDA, Div Imaging Diagnost & Software Reliabil, OSEL, CDRH, Silver Spring, MD USA.
RP Han, M (reprint author), Yonsei Univ, Sch Integrated Technol, Seoul 120749, South Korea.; Han, M (reprint author), Yonsei Univ, Yonsei Inst Convergence Technol, Seoul 120749, South Korea.
NR 12
TC 1
Z9 1
U1 0
U2 0
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-5106-0022-5
J9 PROC SPIE
PY 2016
VL 9787
AR 978717
DI 10.1117/12.2214689
PG 7
WC Optics; Radiology, Nuclear Medicine & Medical Imaging
SC Optics; Radiology, Nuclear Medicine & Medical Imaging
GA BF0CK
UT WOS:000378534200041
ER
PT S
AU Lee, C
Baek, J
Park, S
AF Lee, Changwoo
Baek, Jongduk
Park, Subok
BE Abbey, CK
Kupinski, MA
TI Investigation on location-dependent detectability of a small mass for
digital breast tomosynthesis evaluation
SO MEDICAL IMAGING 2016: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND
TECHNOLOGY ASSESSMENT
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Medical Imaging - Image Perception, Observer Performance,
and Technology Assessment
CY MAR 02-03, 2016
CL San Diego, CA
SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD
DE Model observers; Laguerre-Gauss channels; anatomical background
statistics; location-dependent detectability; digital breast
tomosynthesis
ID CONE-BEAM CT; OF-THE-ART; ALGORITHM; MICROCALCIFICATION; MAMMOGRAPHY;
SIMULATION; PROJECTION; SYSTEM
AB Digital breast tomosynthesis (DBT) is an emerging imaging modality for improved breast cancer detection and diagnosis [1-5]. Numerous efforts have been made to find quantitative metrics associated with mammographic image quality assessment, such as the exponent beta of anatomical noise power spectrum, glandularity, contrast noise ratio, etc. [6-8]. In addition, with the use of Fourier-domain detectability for a task-based assessment of DBT, a stationarity assumption on reconstructed image statistics was often made [9-11], resulting in the use of multiple regions-of-interest (ROIs) from different locations in order to increase sample size. While all these metrics provide some information on mammographic image characteristics and signal detection, the relationship between these metrics and detectability in DBT evaluation has not been fully understood. In this work, we investigated spatial-domain detectability trends and levels as a function of the number of slices N-s at three different ROI locations on the same image slice, where background statistics differ in terms of the aforementioned metrics. Detectabilities for the three ROI locations were calculated using multi-slice channelized Hotelling observers with 2D/3D Laguerre-Gauss channels. Our simulation results show that detectability levels and trends as a function of N-s vary across these three ROI locations. They also show that the exponent beta, mean glandularity, and mean attenuation coefficient vary across the three ROI locations but they do not necessarily predict the ranking of detectability levels and trends across these ROI locations.
C1 [Lee, Changwoo; Baek, Jongduk] Yonsei Univ, Sch Integrated Technol, Seoul 120749, South Korea.
[Lee, Changwoo; Baek, Jongduk] Yonsei Univ, Yonsei Inst Convergence Technol, Seoul 120749, South Korea.
[Park, Subok] US FDA, Div Imaging Diagnost & Software Reliabil, OSEL, CDRH, Silver Spring, MD USA.
RP Park, S (reprint author), 10903 New Hampshire Ave,WO62-31092,Room 3109, Silver Spring, MD 20993 USA.
EM subok.park@fda.hhs.gov
NR 21
TC 0
Z9 0
U1 0
U2 0
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-5106-0022-5
J9 PROC SPIE
PY 2016
VL 9787
AR 97870V
DI 10.1117/12.2216579
PG 9
WC Optics; Radiology, Nuclear Medicine & Medical Imaging
SC Optics; Radiology, Nuclear Medicine & Medical Imaging
GA BF0CK
UT WOS:000378534200029
ER
PT S
AU Sahiner, B
Chen, WJ
Pezeshk, A
Petrick, N
AF Sahiner, Berkman
Chen, Weijie
Pezeshk, Aria
Petrick, Nicholas
BE Abbey, CK
Kupinski, MA
TI Semi-parametric Estimation of the Area Under the Precision-Recall Curve
SO MEDICAL IMAGING 2016: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND
TECHNOLOGY ASSESSMENT
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Medical Imaging - Image Perception, Observer Performance,
and Technology Assessment
CY MAR 02-03, 2016
CL San Diego, CA
SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD
DE Precision-recall curve; receiver operating characteristic curve; area
under curve; information retrieval
AB Precision and recall are two common metrics used in the evaluation of information retrieval systems. By changing the number of retrieved documents, one can obtain a precision-recall curve. The area under the precision-recall curve (AUCPR) has been suggested as a performance measure for information retrieval systems, in a manner similar to the use of the area under the receiver operating characteristic curve in binary classification. Limited work has been performed in the literature to investigate the bias and variance of AUCPR estimators. The goal of our study was to investigate the bias and variability of a semi-parametric binormal method for estimating the AUCPR, and to compare it to other techniques, such as average precision (AP) and lower trapezoid (LT) approximation. We show how AUCPR can be obtained given the binormal model parameters, and how its variance can be estimated using the delta method. We performed simulation experiments with normal and non-normal data, and investigated the effect of sample size and prevalence. Our results indicated that the semi-parametric binormal approach provided AUCPR estimates with small bias and confidence intervals with acceptable coverage when the sample size was large, and the performance of the binormal model was comparable to or better than alternative methods evaluated in this study when the sample size was small. We conclude that the semi-parametric binormal model can be used to accurately estimate the AUCPR, and that the confidence intervals derived from the model can be at least as accurate as from other alternatives, even for non-normal decision variable distributions.
C1 [Sahiner, Berkman; Chen, Weijie; Pezeshk, Aria; Petrick, Nicholas] US FDA, CDRH, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
RP Sahiner, B (reprint author), US FDA, CDRH, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM Berkman.sahiner@fda.hhs.gov
NR 8
TC 0
Z9 0
U1 0
U2 0
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-5106-0022-5
J9 PROC SPIE
PY 2016
VL 9787
AR 97870D
DI 10.1117/12.2216434
PG 7
WC Optics; Radiology, Nuclear Medicine & Medical Imaging
SC Optics; Radiology, Nuclear Medicine & Medical Imaging
GA BF0CK
UT WOS:000378534200012
ER
PT S
AU Wen, GZ
Markey, MK
Park, S
AF Wen, Gezheng
Markey, Mia K.
Park, Subok
BE Abbey, CK
Kupinski, MA
TI Model observer design for detecting multiple abnormalities in anatomical
background images
SO MEDICAL IMAGING 2016: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND
TECHNOLOGY ASSESSMENT
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Medical Imaging - Image Perception, Observer Performance,
and Technology Assessment
CY MAR 02-03, 2016
CL San Diego, CA
SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD
DE Multiple signal detection; channelized Hotelling observer; multifocal
and multicentric cancer; mammographic image evaluation; partial least
squares; Laguerre-Gauss function
ID CLUSTERED LUMPY BACKGROUNDS; BREAST TOMOSYNTHESIS; TEXTURE SYNTHESIS;
GAZE-TRACKING; ACQUISITION; CANCERS; PERCEPTION; SIMULATION; LOCATIONS;
ALGORITHM
AB As psychophysical studies are resource-intensive to conduct, model observers are commonly used to assess and optimize medical imaging quality. Existing model observers were typically designed to detect at most one signal. However, in clinical practice, there may be multiple abnormalities in a single image set (e.g., multifocal and multicentric breast cancers (MMBC)), which can impact treatment planning. Prevalence of signals can be different across anatomical regions, and human observers do not know the number or location of signals a priori. As new imaging techniques have the potential to improve multiple-signal detection (e.g., digital breast tomosynthesis may be more effective for diagnosis of MMBC than planar mammography), image quality assessment approaches addressing such tasks are needed. In this study, we present a model-observer mechanism to detect multiple signals in the same image dataset. To handle the high dimensionality of images, a novel implementation of partial least squares (PLS) was developed to estimate different sets of efficient channels directly from the images. Without any prior knowledge of the background or the signals, the PLS channels capture interactions between signals and the background which provide discriminant image information. Corresponding linear decision templates are employed to generate both image-level and location-specific scores on the presence of signals. Our preliminary results show that the model observer using PLS channels, compared to our first attempts with Laguerre-Gauss channels, can achieve high performance with a reasonably small number of channels, and the optimal design of the model observer may vary as the tasks of clinical interest change.
C1 [Wen, Gezheng] Univ Texas Austin, Dept Elect & Comp Engn, Austin, TX 78712 USA.
[Wen, Gezheng] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA.
[Markey, Mia K.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA.
[Markey, Mia K.] Univ Texas MD Anderson Canc Ctr, Dept Imaging Phys, Houston, TX 77030 USA.
[Park, Subok] US FDA, Div Imaging Diagnost & Software Reliabil, Silver Spring, MD 20993 USA.
RP Wen, GZ (reprint author), Univ Texas Austin, Dept Elect & Comp Engn, Austin, TX 78712 USA.; Wen, GZ (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA.
EM wen.gezheng@utexas.edu; mia.markey@utexas.edu; subok.Park@fda.hhs.gov
NR 34
TC 0
Z9 0
U1 0
U2 0
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-5106-0022-5
J9 PROC SPIE
PY 2016
VL 9787
AR 97870S
DI 10.1117/12.2217665
PG 11
WC Optics; Radiology, Nuclear Medicine & Medical Imaging
SC Optics; Radiology, Nuclear Medicine & Medical Imaging
GA BF0CK
UT WOS:000378534200026
ER
PT S
AU Yngvesson, SK
Karellas, A
Glick, S
Khan, A
Siqueira, PR
Kelly, PA
Peter, BS
AF Yngvesson, Sigfrid K.
Karellas, Andrew
Glick, Stephen
Khan, Ashraf
Siqueira, Paul R.
Kelly, Patrick A.
Peter, Benjamin St.
BE Jansen, ED
TI Breast cancer margin detection with a single frequency terahertz imaging
system
SO OPTICAL INTERACTIONS WITH TISSUE AND CELLS XXVII
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Optical Interactions with Tissue and Cells XXVII
CY FEB 14-17, 2016
CL San Francisco, CA
SP SPIE
DE Breast cancer; medical imaging; reflectivity; refractive index; single
frequency THz imaging (SFTI); THz
ID CONSERVATION SURGERY; SPECTROSCOPY; TECHNOLOGY; CARCINOMA; THERAPY;
DOMAIN; TIME
AB The ability to discern malignant from benign tissue in excised human breast specimens in Breast Conservation Surgery (BCS) was evaluated using a prototype single frequency terahertz radiation. Terahertz (THz) images of the specimens in reflection mode were obtained by employing a gas laser source and mechanical scanning. The images were correlated with optical histological micrographs of the same specimens, and a mean discrimination of 73% was found for five out of six samples using Receiver Operating Characteristic (ROC) analysis. This result is similar to what has previously been obtained using Terahertz pulsed imaging (TPI) techniques. We will discuss the specific advantages of Single frequency THz imaging (SFTI) compared with TPI for potentially allowing the development of much faster, more compact and less expensive cancer imaging systems that could be adapted for employment in the operating room. The system design and characterization of the prototype SFTI system are discussed in detail. The initial results are encouraging but further development of the technology and clinical evaluation is needed to evaluate its feasibility in the clinical environment.
C1 [Yngvesson, Sigfrid K.; Siqueira, Paul R.; Kelly, Patrick A.] Univ Massachusetts, Dept Elect & Comp Engn, Amherst, MA 01003 USA.
[Karellas, Andrew; Khan, Ashraf] Univ Massachusetts, Sch Med, Worcester, MA 01655 USA.
[Glick, Stephen] US FDA, US Dept HHS, Silver Spring, MD 20993 USA.
[Peter, Benjamin St.] Spectral Sci Inc, Burlington, MA 01803 USA.
RP Yngvesson, SK (reprint author), Univ Massachusetts, Dept Elect & Comp Engn, Amherst, MA 01003 USA.
NR 45
TC 0
Z9 0
U1 5
U2 7
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-62841-940-5
J9 PROC SPIE
PY 2016
VL 9706
AR 970603
DI 10.1117/12.2216385
PG 16
WC Engineering, Biomedical; Engineering, Electrical & Electronic; Optics;
Physics, Applied
SC Engineering; Optics; Physics
GA BF0HH
UT WOS:000378852400002
ER
PT S
AU Vogt, WC
Jia, CX
Wear, KA
Garra, BS
Pfefer, TJ
AF Vogt, William C.
Jia, Congxian
Wear, Keith A.
Garra, Brian S.
Pfefer, T. Joshua
BE Oraevsky, AA
Wang, LV
TI Nanoparticle-Enhanced Spectral Photoacoustic Tomography: Effect of
Oxygen Saturation and Tissue Heterogeneity
SO PHOTONS PLUS ULTRASOUND: IMAGING AND SENSING 2016
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Photons Plus Ultrasound - Imaging and Sensing
CY FEB 14-17, 2016
CL San Francisco, CA
SP SPIE, Seno Med Instruments Inc
DE Gold nanorods; tissue phantoms; blood oxygenation; oximetry
ID MEDIA
AB Molecular imaging for breast cancer detection, infectious disease diagnostics and preclinical animal research may be achievable through combined use of targeted exogenous agents such as nanoparticles and spectral Photoacoustic Tomography (PAT). However, tissue heterogeneity can alter fluence distributions and acoustic propagation, corrupting measured PAT absorption spectra and complicating in vivo nanoparticle detection and quantitation Highly absorptive vascular structures represent a common confounding factor, and variations in vessel hemoglobin saturation (SO2) may alter spectral content of signals from adjacent/deeper regions. To evaluate the impact of this effect on PAT nanoparticle detectability, we constructed heterogeneous phantoms with well-characterized channel-inclusion geometries and biologically relevant optical and acoustic properties. Phantoms contained an array of tubes at several depths filled with hemoglobin solutions doped with varying concentrations of gold nanorods with an absorption peak at 780 nm. Both overlying and target network SO2 was tuned using sodium dithionite. Phantoms were imaged from 700 to 900 nm using a custom PAT system comprised of a tunable pulsed laser and a research-grade ultrasound system. Recovered nanoparticle spectra were analyzed and compared with results from both spectrophotometry and PAT data from water immersed tubes containing blood and nanoparticle solutions. Results suggested that nanoparticle selection for a given PAT application should take into account expected oxygenation states of both target blood vessel and background tissue oxygenation to achieve optimal performance.
C1 [Vogt, William C.; Jia, Congxian; Wear, Keith A.; Garra, Brian S.; Pfefer, T. Joshua] US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20093 USA.
RP Pfefer, TJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20093 USA.
EM Joshua.Pfefer@fda.hhs.gov
NR 11
TC 0
Z9 0
U1 4
U2 4
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-62841-942-9
J9 PROC SPIE
PY 2016
VL 9708
AR 97081H
DI 10.1117/12.2213468
PG 7
WC Optics; Radiology, Nuclear Medicine & Medical Imaging
SC Optics; Radiology, Nuclear Medicine & Medical Imaging
GA BF0AZ
UT WOS:000378437000050
ER
PT J
AU Nnaji, CN
Mach, PM
Acheampong, JS
Falconer, TM
Verbeck, GF
AF Nnaji, Chinyere N.
Mach, Phillip M.
Acheampong, Jason S.
Falconer, Travis M.
Verbeck, Guido F.
TI Analysis of trace amounts of adulterants found in powders/supplements
utilizing Raman spectroscopy coupled to direct analyte-probed
nanoextraction-nanospray ionization-mass spectrometry
SO ANALYTICAL METHODS
LA English
DT Article
ID DIETARY-SUPPLEMENTS; SYNTHETIC ADULTERANTS; LIQUID-CHROMATOGRAPHY;
IMAGING METHODS; INFANT FORMULA; POWDERED MILK; MELAMINE; MS;
SIBUTRAMINE; EXTRACTION
AB In the United States, all food products have to be regulated to inform the consumers of the ingredients contained within. Some ingredients are not included on the label and yet are still found in the products. Presented is a Raman imaging technique for rapid, nondestructive, and spatially relevant localization of adulterants in powders. Raman spectroscopy followed by direct analyte-probed nanoextraction coupled to nanospray ionization-mass spectrometry allows rapid determination of the presence of each adulterant, leading to positive identifications such as melamine. The location and identification of these trace particles can then be extracted using a nanomanipulator. The nanomanipulation technique uses a solvent filled capillary tip which can be positioned on the particle of interest. Direct mass spectrometric analysis via nanospray of the particulate of interest eliminates time consuming chromatographic techniques prior to mass spectrometry analysis. This coupled technique combines rapid Raman spectroscopy techniques with direct mass spectrometry to confirm the presence of an adulterant. This technique was applied to an FDA supplied test sample, in which sibutramine, phenolphthalein, and melamine were confirmed to be present.
C1 [Nnaji, Chinyere N.; Mach, Phillip M.; Acheampong, Jason S.; Verbeck, Guido F.] Univ N Texas, Dept Chem, Denton, TX 76203 USA.
[Falconer, Travis M.] US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA.
RP Verbeck, GF (reprint author), Univ N Texas, Dept Chem, Denton, TX 76203 USA.
EM gverbeck@unt.edu
FU Intramural FDA HHS [FD999999]
NR 53
TC 0
Z9 0
U1 5
U2 6
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1759-9660
EI 1759-9679
J9 ANAL METHODS-UK
JI Anal. Methods
PY 2016
VL 8
IS 24
BP 4798
EP 4807
DI 10.1039/c6ay00828c
PG 10
WC Chemistry, Analytical; Food Science & Technology; Spectroscopy
SC Chemistry; Food Science & Technology; Spectroscopy
GA DP1DV
UT WOS:000378231600003
PM 27482293
ER
PT J
AU Pillai, KV
Gray, PJ
Tien, CC
Bleher, R
Sung, LP
Duncan, TV
AF Pillai, Karthik V.
Gray, Patrick J.
Tien, Chun-Chieh
Bleher, Reiner
Sung, Li-Piin
Duncan, Timothy V.
TI Environmental release of core-shell semiconductor nanocrystals from
free-standing polymer nanocomposite films
SO ENVIRONMENTAL SCIENCE-NANO
LA English
DT Article
ID FOOD-CONTACT MATERIALS; EXPOSURE ASSESSMENT; PACKAGING APPLICATIONS;
SILVER NANOPARTICLES; CONSUMER PRODUCTS; MIGRATION; POLYETHYLENE;
NANOSILVER; COMPOSITES; NANOCLAY
AB Concomitant with the development of polymer nanocomposite (PNC) technologies across numerous industries is an expanding awareness of the uncertainty with which engineered nanoparticles embedded within these materials may be released into the external environment, particularly liquid media. Recently there has been an interest in evaluating potential exposure to nanoscale fillers from PNCs, but existing studies often rely upon uncharacterized, poor quality, or proprietary materials, creating a barrier to making general mechanistic conclusions about release phenomena. In this study we employed semiconductor nanoparticles (quantum dots, QDs) as model nanofillers to quantify potential release into liquid media under specific environmental conditions. QDs of two sizes were incorporated into low-density polyethylene by melt compounding and the mixtures were extruded as free-standing fluorescent films. These films were subjected to tests under conditions intended to accelerate potential release of embedded particles or dissolved residuals into liquid environments. Using inductively-coupled plasma mass spectrometry and laser scanning confocal microscopy, it was found that the acidity of the external medium, exposure time, and small differences in particle size (on the order of a few nm) all play pivotal roles in release kinetics. Particle dissolution was found to play a major if not dominant role in the release process. This paper also presents the first evidence that internally embedded nanoparticles contribute to the mass transfer, an observation made possible via the use of a model system that was deliberately designed to probe the complex relationships between nanoparticle-enabled plastics and the environment.
C1 [Pillai, Karthik V.; Gray, Patrick J.; Duncan, Timothy V.] US FDA, Ctr Food Safety & Appl Nutr, 6502 South Archer Rd, Bedford Pk, IL 60501 USA.
[Tien, Chun-Chieh; Sung, Li-Piin] NIST, Polymer Mat Grp, 100 Bur Dr, Gaithersburg, MD 20899 USA.
[Bleher, Reiner] Northwestern Univ, Northwestern Univ Atom & Nanoscale Characterizat, Evanston, IL 60208 USA.
[Bleher, Reiner] Northwestern Univ, Dept Mat Sci & Engn, Evanston, IL 60208 USA.
RP Duncan, TV (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 6502 South Archer Rd, Bedford Pk, IL 60501 USA.
EM timothy.duncan@fda.hhs.gov
OI Gray, Patrick/0000-0002-8248-2749
FU FDA/CFSAN; MRSEC program at the Materials Research Center [NSF
DMR-1121262]; International Institute for Nanotechnology (IIN); State of
Illinois, through the IIN
FX The authors gratefully acknowledge Glenn J. Bastiaans, Ph. D., President
of NanoOptical Materials, for helpful discussions related to QD
performance and composition. The authors also thank FDA/CFSAN for
financial support of this work. This work made use of the EPIC facility
(NUANCE Center-Northwestern University), which has received support from
the MRSEC program (NSF DMR-1121262) at the Materials Research Center;
the International Institute for Nanotechnology (IIN); and the State of
Illinois, through the IIN.
NR 48
TC 2
Z9 2
U1 6
U2 12
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 2051-8153
EI 2051-8161
J9 ENVIRON SCI-NANO
JI Environ.-Sci. Nano
PY 2016
VL 3
IS 3
BP 657
EP 669
DI 10.1039/c6en00064a
PG 13
WC Chemistry, Multidisciplinary; Environmental Sciences; Nanoscience &
Nanotechnology
SC Chemistry; Environmental Sciences & Ecology; Science & Technology -
Other Topics
GA DP1IZ
UT WOS:000378245000016
PM 27529026
ER
PT S
AU Choi, M
Alam, N
Dahal, E
Ghammraoui, B
Badano, A
AF Choi, Mina
Alam, Nadia
Dahal, Eshan
Ghammraoui, Bahaa
Badano, Aldo
BE Gimi, B
Krol, A
TI Alzheimer's disease imaging biomarkers using small-angle x-ray
scattering
SO MEDICAL IMAGING 2016-BIOMEDICAL APPLICATIONS IN MOLECULAR, STRUCTURAL,
AND FUNCTIONAL IMAGING
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT SPIE Biomedical Applications in Molecular, Structural and Functional
Imaging Conference
CY MAR 01-03, 2016
CL San Diego, CA
SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, imXPAD
DE Alzheimer's disease; Small angle x-ray scattering; cross sections; Monte
Carlo simulations; biomarkers; amyloid beta
AB There is a need for novel imaging, techniques for the earlier detection of Alzheimer's disease (All). Two hallmarks of AD are amyloid beta (A beta) plaques and tau tangles that are formed in the brain. Well-characterized x-ray cross sections of A beta and tau proteins in a variety of structural states could potentially be used as AD biomarkers for small-angle x-ray scattering (SANS) imaging without the need for injectable probes or contrast agents. First, however, the protein structures must be controlled and measured to determine accurate biomarkers for SAXS imaging. Here we report SAXS measurements of A beta(42) and tau(352) in a 50% dimethyl sulfoxide (DMSO) solution in which these proteins are believed to remain monomeric because of the stabilizing interaction of DMSO solution. Our SANS analysis showed the aggregation of both proteins. in particular, we found that the aggregation of A beta(42) slowly progresses with time in comparison to tau(352) that aggregates at a faster rate and reaches a steady-state. Furthermore, the measured signals were compared to the theoretical SANS profiles of A beta(42) monomer, A beta(42) fibril, and tau(352) that were computed from their respective protein data bank structures. We have begun the work to systematically control the structural states of these proteins in vitro using various solvent conditions. Our future work is to utilize the distinct SAXS profiles of various structural states of A beta and tau to build a library of signals of interest for SAXS imaging in brain tissue.
C1 [Choi, Mina; Dahal, Eshan; Badano, Aldo] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA.
[Choi, Mina; Alam, Nadia; Dahal, Eshan; Ghammraoui, Bahaa; Badano, Aldo] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Badano, A (reprint author), Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA.; Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
EM aldo.badano@fda.hhs.gov
OI badano, aldo/0000-0003-3712-6670
NR 16
TC 0
Z9 0
U1 1
U2 1
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-5106-0023-2
J9 PROC SPIE
PY 2016
VL 9788
AR 978802
DI 10.1117/12.2217408
PG 7
WC Optics; Radiology, Nuclear Medicine & Medical Imaging
SC Optics; Radiology, Nuclear Medicine & Medical Imaging
GA BE9WB
UT WOS:000378223800002
ER
PT S
AU Badal, A
AF Badal, Andreu
BE Kontos, D
Flohr, TG
Lo, JY
TI Prototype adaptive bow-tie filter based on spatial exposure time
modulation
SO MEDICAL IMAGING 2016: PHYSICS OF MEDICAL IMAGING
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Medical Imaging - Physics of Medical Imaging
CY FEB 28-MAR 02, 2016
CL San Diego, CA
SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD, Carestream Hlth Inc, GE Healthcare
DE bow-tie filter; dynamic filter; x-ray beam shaping; adaptive imaging
ID CT
AB In recent years, there has been an increased interest in the development of dynamic bow -tie filters that are able to provide patient-specific x-ray beam shaping. We introduce the first physical prototype of a new adaptive bow-tie filter design based on the concept of "spatial exposure time modulation." While most existing bow -tie filters operate by attenuating the radiation beam differently in different locations using partially attenuating objects, the presented filter shapes the radiation field using two movable completely radio-opaque collimators. The aperture and speed of the collimators is modulated in synchrony with the x-ray exposure to selectively block the radiation emitted to different parts of the object. This mode of operation does not allow the reproduction of every possible attenuation profile, but it can reproduce the profile of any object with an attenuation profile monotonically decreasing from the center to the periphery, such as an object with an elliptical cross section. Therefore, the new adaptive filter provides the same advantages as the currently existing static bow -tie filters, which are typically designed to work for a pre-determined cylindrical object at a fixed distance from the source, and provides the additional capability to adapt its performance at image acquisition time to better compensate for the actual diameter and location of the imaged object. A detailed description of the prototype filter, the implemented control methods, and a preliminary experimental validation of its performance are presented.
C1 [Badal, Andreu] US FDA, Div Imaging Diagnost & Software Reliabil, OSEL, CDRH, Silver Spring, MD 20993 USA.
RP Badal, A (reprint author), US FDA, Div Imaging Diagnost & Software Reliabil, OSEL, CDRH, Silver Spring, MD 20993 USA.
NR 8
TC 0
Z9 0
U1 0
U2 0
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-5106-0018-8
J9 PROC SPIE
PY 2016
VL 9783
DI 10.1117/12.2217235
PG 7
WC Optics; Physics, Multidisciplinary; Radiology, Nuclear Medicine &
Medical Imaging
SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging
GA BE9YS
UT WOS:000378352900113
ER
PT S
AU Choi, M
Ghammraoui, B
Badal, A
Badano, A
AF Choi, Mina
Ghammraoui, Bahaa
Badal, Andreu
Badano, Aldo
BE Kontos, D
Flohr, TG
Lo, JY
TI Method to study sample object size limit of small-angle x-ray scattering
computed tomography
SO MEDICAL IMAGING 2016: PHYSICS OF MEDICAL IMAGING
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Medical Imaging - Physics of Medical Imaging
CY FEB 28-MAR 02, 2016
CL San Diego, CA
SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD, Carestream Hlth Inc, GE Healthcare
DE Small angle x-ray scattering imaging; Monte Carlo simulations; x-ray
phantoms; dose estimation; small animal imaging systems
AB Small-angle x-ray scattering (SAXS) imaging is an emerging medical tool that can be used for in vivo detailed tissue characterization and has the potential to provide added contrast to conventional x-ray projection and CT imaging. We used a publicly available MC-GPU code to simulate x-ray trajectories in a SAXS-CT geometry for a target material embedded in a water background material with varying sample sizes (1, 3, 5, and 10 mm). Our target materials were water solution of gold nanoparticle (GNP) spheres with a radius of 6 nm and a water solution with dissolved serum albumin (BSA) proteins due to their well-characterized scatter profiles at small angles and highly scattering properties. The background material was water. Our objective is to study how the reconstructed scatter profile degrades at larger target imaging depths and increasing sample sizes. We have found that scatter profiles of the GNP in water can still be reconstructed at depths up to 5 mm embedded at the center of a 10 mm sample. Scatter profiles of BSA in water were also reconstructed at depths up to 5 mm in a 10 mm sample but with noticeable signal degradation as compared to the GNP sample. This work presents a method to study the sample size limits for future SAXS-CT imaging systems.
C1 [Choi, Mina; Badano, Aldo] Univ Maryland, College Pk, MD 20742 USA.
[Ghammraoui, Bahaa; Badal, Andreu; Badano, Aldo] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Choi, M (reprint author), Univ Maryland, College Pk, MD 20742 USA.
EM aldo.badano@fda.hhs.gov
OI badano, aldo/0000-0003-3712-6670
NR 11
TC 0
Z9 0
U1 1
U2 2
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-5106-0018-8
J9 PROC SPIE
PY 2016
VL 9783
AR 97831Z
DI 10.1117/12.2216325
PG 6
WC Optics; Physics, Multidisciplinary; Radiology, Nuclear Medicine &
Medical Imaging
SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging
GA BE9YS
UT WOS:000378352900068
ER
PT S
AU Clark, M
Ghammraoui, B
Badal, A
AF Clark, Matthew
Ghammraoui, Bahaa
Badal, Andreu
BE Kontos, D
Flohr, TG
Lo, JY
TI Reproducing 2D Breast Mammography Images with 3D Printed Phantoms
SO MEDICAL IMAGING 2016: PHYSICS OF MEDICAL IMAGING
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Medical Imaging - Physics of Medical Imaging
CY FEB 28-MAR 02, 2016
CL San Diego, CA
SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD, Carestream Hlth Inc, GE Healthcare
DE mammography; breast phantoms; 3D printing
AB Mammography is currently the standard imaging modality used to screen women for breast abnormalities and, as a result, it is a tool of great importance for the early detection of breast cancer. Physical phantoms are commonly used as surrogates of breast tissue to evaluate some aspects of the performance of mammography systems. However, most phantoms do not reproduce the anatomic heterogeneity of real breasts. New fabrication technologies, such as 3D printing, have created the opportunity to build more complex, anatomically realistic breast phantoms that could potentially assist in the evaluation of mammography systems. The primary objective of this work is to present a simple, easily reproducible methodology to design and print 3D objects that replicate the attenuation profile observed in real 2D mammograms. The secondary objective is to evaluate the capabilities and limitations of the competing 3D printing technologies, and characterize the x-ray properties of the different materials they use. Printable phantoms can be created using the open-source code introduced in this work, which processes a raw mammography image to estimate the amount of x-ray attenuation at each pixel, and outputs a triangle mesh object that encodes the observed attenuation map. The conversion from the observed pixel gray value to a column of printed material with equivalent attenuation requires certain assumptions and knowledge of multiple imaging system parameters, such as x-ray energy spectrum, source-to-object distance, compressed breast thickness, and average breast material attenuation. A detailed description of the new software, a characterization of the printed materials using x-ray spectroscopy, and an evaluation of the realism of the sample printed phantoms are presented.
C1 [Ghammraoui, Bahaa; Badal, Andreu] US FDA, Div Imaging Diagnost & Software Reliabil, OSEL, CDRH, Silver Spring, MD USA.
[Clark, Matthew] Univ Maryland, Mech Engn, College Pk, MD 20742 USA.
RP Clark, M (reprint author), Univ Maryland, Mech Engn, College Pk, MD 20742 USA.
NR 7
TC 0
Z9 0
U1 3
U2 3
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-5106-0018-8
J9 PROC SPIE
PY 2016
VL 9783
AR 97830B
DI 10.1117/12.2217215
PG 9
WC Optics; Physics, Multidisciplinary; Radiology, Nuclear Medicine &
Medical Imaging
SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging
GA BE9YS
UT WOS:000378352900010
ER
PT S
AU Fang, Y
Badano, A
AF Fang, Yuan
Badano, Aldo
BE Kontos, D
Flohr, TG
Lo, JY
TI DQE simulation of a-Se x-ray detectors using ARTEMIS
SO MEDICAL IMAGING 2016: PHYSICS OF MEDICAL IMAGING
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Medical Imaging - Physics of Medical Imaging
CY FEB 28-MAR 02, 2016
CL San Diego, CA
SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD, Carestream Hlth Inc, GE Healthcare
DE Monte Carlo simulation; amorphous selenium; ARTEMIS; detective quantum
efficiency
ID AMORPHOUS SELENIUM; QUANTUM EFFICIENCY; DIGITAL RADIOLOGY; SCREENS;
ABSORPTION; ENERGY; NOISE
AB Detective Quantum Efficiency (DQE) is one of the most important image quality metrics for evaluating the spatial resolution performance of flat-panel x-ray detectors. In this work, we simulate the DQE of amorphous selenium (a-Se) x-ray detectors with a detailed Monte Carlo transport code (ARTEMIS) for modeling semiconductor-based direct x-ray detectors. The transport of electron-hole pairs is achieved with a spatiotemporal model that accounts for recombination and trapping of carriers and Coulombic effects of space charge and external applied electric field. A range of x-ray energies has been simulated from 10 to 100 keV. The DQE results can be used to study the spatial resolution characteristics of detectors at different energies.
C1 [Fang, Yuan] US FDA, Off Vitro Diagnost & Radiol Hlth, Ctr Devices & Radiol Hlth, Diagnost Xray Syst Branch,Div Radiol Hlth, Silver Spring, MD 20993 USA.
[Badano, Aldo] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Imaging Diagnost & Software Reliabil, Silver Spring, MD USA.
RP Fang, Y (reprint author), US FDA, Off Vitro Diagnost & Radiol Hlth, Ctr Devices & Radiol Hlth, Diagnost Xray Syst Branch,Div Radiol Hlth, Silver Spring, MD 20993 USA.
EM yuan.fang@fda.hhs.gov
OI badano, aldo/0000-0003-3712-6670
NR 21
TC 0
Z9 0
U1 0
U2 0
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-5106-0018-8
J9 PROC SPIE
PY 2016
VL 9783
AR 978314
DI 10.1117/12.2214805
PG 6
WC Optics; Physics, Multidisciplinary; Radiology, Nuclear Medicine &
Medical Imaging
SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging
GA BE9YS
UT WOS:000378352900038
ER
PT S
AU Gavrielides, MA
Li, Q
Zeng, RP
Gong, Q
Myers, K
Sahiner, B
Petrick, N
AF Gavrielides, Marios A.
Li, Qin
Zeng, Rongping
Gong, Qi
Myers, Kyle
Sahiner, Berkman
Petrick, Nicholas
BE Kontos, D
Flohr, TG
Lo, JY
TI Detectable change of lung nodule volume with CT in a phantom study with
high and low signal to background contrast
SO MEDICAL IMAGING 2016: PHYSICS OF MEDICAL IMAGING
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Medical Imaging - Physics of Medical Imaging
CY FEB 28-MAR 02, 2016
CL San Diego, CA
SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD, Carestream Hlth Inc, GE Healthcare
DE lung nodule; volumetric computed tomography; change analysis; minimum
detectable change; protocol; quantitative imaging biomarkers
ID GROUND-GLASS OPACITY; PULMONARY NODULES; RECONSTRUCTION
AB In previous work we developed a method for predicting the minimum detectable change (MDC) in nodule volume based on volumetric CT measurements. MDC was defined as the minimum increase/decrease in a nodule volume distinguishable from the baseline measurement at a specified level of detection performance, assessed using the area under the ROC curve (AUC). In this work we derived volume estimates of a set of synthetic nodules and calculated the detection performance for distinguishing them from baseline measurements. Eight spherical objects of 100HU radiodensity ranging in diameter from 5.0mm to 5.75mm and 8.0mm to 8.75mm with 0.25mm increments were placed in an anthropomorphic phantom with either no background (high-contrast task) or gelatin background (low-contrast task). The baseline was defined as 5.0mm for the first set of nodules and 8.0mm for the second set. The phantom was scanned using varying exposures, and reconstructed with slice thickness of 0.75, 1.5, and 3.0mm and two reconstruction kernels (standard and smooth). Volume measurements were derived using a previously developed matched- filter approach. Results showed that nodule size, slice thickness, and nodule-to-background contrast affected detectable change in nodule volume when using our volume estimator and the acquisition settings from our study. We also compared our experimental results to the values estimated by our previously-developed MDC prediction method. We found that experimental data for the 8mm baseline nodules matched very well with our predicted values of MDC. These results support considering the use of this metric when standardizing imaging protocols for lung nodule size change assessment.
C1 [Gavrielides, Marios A.; Li, Qin; Zeng, Rongping; Gong, Qi; Myers, Kyle; Sahiner, Berkman; Petrick, Nicholas] US FDA, Div Imaging Diagnost & Software Reliabil, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Gavrielides, MA (reprint author), US FDA, Div Imaging Diagnost & Software Reliabil, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
NR 19
TC 0
Z9 0
U1 0
U2 0
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-5106-0018-8
J9 PROC SPIE
PY 2016
VL 9783
AR 978329
DI 10.1117/12.2217887
PG 8
WC Optics; Physics, Multidisciplinary; Radiology, Nuclear Medicine &
Medical Imaging
SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging
GA BE9YS
UT WOS:000378352900076
ER
PT S
AU Glick, SJ
Makeev, A
AF Glick, Stephen J.
Makeev, Andrey
BE Kontos, D
Flohr, TG
Lo, JY
TI Optimal Exposure Techniques for Iodinated Contrast Enhanced Breast CT
SO MEDICAL IMAGING 2016: PHYSICS OF MEDICAL IMAGING
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Medical Imaging - Physics of Medical Imaging
CY FEB 28-MAR 02, 2016
CL San Diego, CA
SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD, Carestream Hlth Inc, GE Healthcare
DE Breast CT; X-ray Filters; Iodinated Contrast Imaging
ID SYSTEMS; MAMMOGRAMS; RADIATION; NOISE
AB Screening for breast cancer using mammography has been very successful in the effort to reduce breast cancer mortality, and its use has largely resulted in the 30% reduction in breast cancer mortality observed since 1990 [1]. However, diagnostic mammography remains an area of breast imaging that is in great need for improvement. One imaging modality proposed for improving the accuracy of diagnostic workup is iodinated contrast-enhanced breast CT [2]. In this study, a mathematical framework is used to evaluate optimal exposure techniques for contrast-enhanced breast CT. The ideal observer signal-to-noise ratio (i.e., d') figure-of-merit is used to provide a task perfoimance based assessment of optimal acquisition parameters under the assumptions of a linear, shift-invariant imaging system. A parallel-cascade model was used to estimate signal and noise propagation through the detector, and a realistic lesion model with iodine uptake was embedded into a structured breast background. Ideal observer perfoimance was investigated across kVp settings, filter materials, and filter thickness. Results indicated many kVp spectra/filter combinations can improve perfoimance over currently used x-ray spectra.
C1 [Glick, Stephen J.; Makeev, Andrey] US FDA, Div Imaging Diagnost & Software Reliabil, OSEL, CDRH, Silver Spring, MD 20993 USA.
RP Glick, SJ (reprint author), US FDA, Div Imaging Diagnost & Software Reliabil, OSEL, CDRH, Silver Spring, MD 20993 USA.
NR 16
TC 0
Z9 0
U1 0
U2 0
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-5106-0018-8
J9 PROC SPIE
PY 2016
VL 9783
AR 97832N
DI 10.1117/12.2216806
PG 6
WC Optics; Physics, Multidisciplinary; Radiology, Nuclear Medicine &
Medical Imaging
SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging
GA BE9YS
UT WOS:000378352900089
ER
PT S
AU Graff, CG
AF Graff, Christian G.
BE Kontos, D
Flohr, TG
Lo, JY
TI A New, Open-Source, Multi-Modality Digital Breast Phantom
SO MEDICAL IMAGING 2016: PHYSICS OF MEDICAL IMAGING
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Medical Imaging - Physics of Medical Imaging
CY FEB 28-MAR 02, 2016
CL San Diego, CA
SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD, Carestream Hlth Inc, GE Healthcare
DE breast; x-ray; MRI; phantom
ID SOFTWARE PHANTOM; NOISE
AB Art anthropomorphic digital breast phantom has been developed with the goal of generating random voxelized breast models that capture the anatomic variability observed in vivo. This is a new phantom and is not based OR existing digital breast phantoms or segmentation of patient images. It has been designed at the outset to be modality agnostic (i.e., suitable for use in modeling x-ray based imaging systems, magnetic resonance imaging, and potentially other imaging systems) and open source so that users may freely modify the phantom to suit a particular study. In this work we describe the modeling techniques that have been developed, the capabilities and novel features of this phantom, and study simulated images produced from it. Starting from a base quadric, a series of deformations are performed to create a breast with a particular volume and shape. Initial glandular compartments are generated using a. Voronoi technique and a. ductal tree structure with terminal duct lobular units is grown from the nipple into each compartment. An additional step involving the creation of fat and glandular lobules using a Perlin noise function is performed to create more realistic glandular/fat tissue interfaces and generate a Cooper's ligament network. A vascular tree is grown front the chest muscle into the breast tissue. Breast compression is performed using a neo-Hookean elasticity model. We show simulated rnammographic and T-1-weightexl MRI images and study properties of these images.
C1 [Graff, Christian G.] US FDA, Div Imaging Diagnost & Software Reliabil, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
RP Graff, CG (reprint author), US FDA, Div Imaging Diagnost & Software Reliabil, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM christian.graff@fda.hhs.gov
NR 16
TC 3
Z9 3
U1 1
U2 2
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-5106-0018-8
J9 PROC SPIE
PY 2016
VL 9783
AR 978309
DI 10.1117/12.2216312
PG 10
WC Optics; Physics, Multidisciplinary; Radiology, Nuclear Medicine &
Medical Imaging
SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging
GA BE9YS
UT WOS:000378352900008
ER
PT S
AU Ikejimba, L
Glick, SJ
Samei, E
Lo, JY
AF Ikejimba, Lynda
Glick, Stephen J.
Samei, Ehsan
Lo, Joseph Y.
BE Kontos, D
Flohr, TG
Lo, JY
TI Comparison of model and human observer performance in FFDM, DBT, and
synthetic mammography
SO MEDICAL IMAGING 2016: PHYSICS OF MEDICAL IMAGING
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Medical Imaging - Physics of Medical Imaging
CY FEB 28-MAR 02, 2016
CL San Diego, CA
SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD, Carestream Hlth Inc, GE Healthcare
DE Anthropomorphic phantom; Digital breast tomosynthesis; Contrast detail;
Model observer; Synthetic mammography
ID BREAST TOMOSYNTHESIS; IMAGE QUALITY; OPTIMIZATION; ACQUISITION; NOISE
AB Reader studies are important in assessing breast imaging systems. The purpose of this work was to assess task-based perfounance of full field digital mammography (FFDM), digital breast tomosynthesis (DBT), and synthetic mammography (SM) using different phantom types, and to determine an accurate observer model for human readers.
Images were acquired on a Hologic Selenia Dimensions system with a unifoun and anthropomorphic phantom. A contrast detail insert of small, low-contrast disks was created using an inkjet printer with iodine-doped ink and inserted in the phantoms. The disks varied in diameter from 210 to 630 mu m, and in contrast from 1.1% contrast to 2.2% in regular increments. Human and model observers performed a 4-alternative forced choice experiment. The models were a non-prewhitening matched filter with eye model (NPWE) and a channelized Hotelling observer with either Gabor channels (Gabor-CHO) or Laguerre-Gauss channels (LG-CHO).
With the given phantoms, reader scores were higher in FFDM and DBT than SM. The structure in the phantom background had a bigger impact on outcome for DBT than for FFDM or SM. All three model observers showed good correlation with humans in the unifoun background, with p between 0.89 and 0.93. However, in the structured background, only the CHOs had high correlation, with p=0.92 for Gabor-CHO, 0.90 for LG-CHO, and 0.77 for NPWE.
Because results of any analysis can depend on the phantom structure, conclusions of modality perfounance may need to be taken in the context of an appropriate model observer and a realistic phantom.
C1 [Ikejimba, Lynda; Samei, Ehsan; Lo, Joseph Y.] Duke Univ, Med Phys Grad Program, Carl E Ravin Adv Imaging Labs, Dept Radiol, Durham, NC 27708 USA.
[Ikejimba, Lynda; Glick, Stephen J.] US FDA, Div Imaging Diagnost & Software Reliabil, OSEL, CDRH, Rockville, MD 20857 USA.
[Samei, Ehsan; Lo, Joseph Y.] Duke Univ, Dept Elect & Comp Engn, Dept Biomed Engn, Durham, NC USA.
[Samei, Ehsan] Duke Univ, Dept Phys, Durham, NC USA.
RP Ikejimba, L (reprint author), Duke Univ, Med Phys Grad Program, Carl E Ravin Adv Imaging Labs, Dept Radiol, Durham, NC 27708 USA.; Ikejimba, L (reprint author), US FDA, Div Imaging Diagnost & Software Reliabil, OSEL, CDRH, Rockville, MD 20857 USA.
EM lci@duke.edu
NR 22
TC 1
Z9 1
U1 0
U2 0
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-5106-0018-8
J9 PROC SPIE
PY 2016
VL 9783
AR 978325
DI 10.1117/12.2216858
PG 10
WC Optics; Physics, Multidisciplinary; Radiology, Nuclear Medicine &
Medical Imaging
SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging
GA BE9YS
UT WOS:000378352900072
ER
PT S
AU Li, Q
Liu, ST
Myers, K
Gavrielides, MA
Zeng, RP
Sahiner, B
Petrick, N
AF Li, Qin
Liu, Songtao
Myers, Kyle
Gavrielides, Marios A.
Zeng, Rongping
Sahiner, Berkman
Petrick, Nicholas
BE Kontos, D
Flohr, TG
Lo, JY
TI Calcium scoring with dual-energy CT in men and women: an anthropomorphic
phantom study
SO MEDICAL IMAGING 2016: PHYSICS OF MEDICAL IMAGING
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Medical Imaging - Physics of Medical Imaging
CY FEB 28-MAR 02, 2016
CL San Diego, CA
SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD, Carestream Hlth Inc, GE Healthcare
DE Coronary calcium scoring; dual-energy computed tomography; phantom
study; gender differences; quantitative imaging; coronary imaging
ID CORONARY-ARTERY CALCIUM; INITIAL-EXPERIENCE; QUANTIFICATION;
ANGIOGRAPHY; PRINCIPLES
AB This work aimed to quantify and compare the potential impact of gender differences on coronary artery calcium scoring with dual-energy CT. An anthropomorphic thorax phantom with four synthetic heart vessels (diameter 3-4.5 mm: female/male left main and left circumflex artery) were scanned with and without female breast plates. Ten repeat scans were acquired in both single- and dual-energy modes and reconstructed at six reconstruction settings: two slice thicknesses (3 mm, 0.6 mm) and three reconstruction algorithms (FBP, IR3, IRS). Agatston and calcium volume scores were estimated from the reconstructed data using a segmentation-based approach. Total calcium score (summation of four vessels), and male/female calcium scores (summation of male/female vessels scanned in phantom without/with breast plates) were calculated accordingly.
Both Agatston and calcium volume scores were found comparable between single- and dual-energy scans (Pearson r= 0.99, p<0.05). The total calcium scores were larger for the thinner slice thickness. Among the scores obtained from the three reconstruction algorithms, FBP yielded the highest and IRS yielded the lowest scores. The total calcium scores from the phantom without breast plates were significantly larger than those from the phantom with breast plates, and the difference increased with the stronger denoising in iterative algorithm and with thicker slices. Both gender-based anatomical differences and vessel size impacted the calcium scores. The calcium volume scores tended to be underestimated when the vessels were smaller. These findings are valuable for understanding inconsistencies between women and men in calcium scoring, and for standardizing imaging protocols for improved gender-specific calcium scoring.
C1 [Li, Qin; Myers, Kyle; Gavrielides, Marios A.; Zeng, Rongping; Sahiner, Berkman; Petrick, Nicholas] US FDA, CDRH OSEL DIDSR, Silver Spring, MD 20993 USA.
[Liu, Songtao] US FDA, CDRH OIR DRH DXRS, Silver Spring, MD USA.
RP Li, Q (reprint author), US FDA, CDRH OSEL DIDSR, Silver Spring, MD 20993 USA.
NR 11
TC 0
Z9 0
U1 0
U2 0
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-5106-0018-8
J9 PROC SPIE
PY 2016
VL 9783
AR 978346
DI 10.1117/12.2216105
PG 7
WC Optics; Physics, Multidisciplinary; Radiology, Nuclear Medicine &
Medical Imaging
SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging
GA BE9YS
UT WOS:000378352900142
ER
PT S
AU Makeev, A
Ikejimba, L
Lo, JY
Glick, SJ
AF Makeev, Andrey
Ikejimba, Lynda
Lo, Joseph Y.
Glick, Stephen J.
BE Kontos, D
Flohr, TG
Lo, JY
TI Investigation of Optimal Parameters for Penalized Maximum-Likelihood
Reconstruction Applied to Iodinated Contrast-Enhanced Breast CT
SO MEDICAL IMAGING 2016: PHYSICS OF MEDICAL IMAGING
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Medical Imaging - Physics of Medical Imaging
CY FEB 28-MAR 02, 2016
CL San Diego, CA
SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD, Carestream Hlth Inc, GE Healthcare
DE Penalized maximum likelihood; breast CT; iodine-doped ink printed
phantom; Hotelling observer
AB Although digital mammography has reduced breast cancer mortality by approximately 30%, sensitivity and specificity are still far from perfect. In particular, the performance of mammography is especially limited for women with dense breast tissue. Two out of every three biopsies performed in the U.S. are unnecessary, thereby resulting in increased patient anxiety, pain, and possible complications. One promising tomographic breast imaging method that has recently been approved by the FDA is dedicated breast computed tomography (BCT). However, visualizing lesions with BCT can still be challenging for women with dense breast tissue due to the minimal contrast for lesions surrounded by fibroglandular tissue. In recent years there has been renewed interest in improving lesion conspicuity in x-ray breast imaging by administration of an iodinated contrast agent. Due to the fully 3-D imaging nature of BCT, as well as sub-optimal contrast enhancement while the breast is under compression with mammography and breast tomosynthesis, dedicated BCT of the uncompressed breast is likely to offer the best solution for injected contrast-enhanced x-ray breast imaging. It is well known that use of statistically-based iterative reconstruction in CT results in improved image quality at lower radiation dose. Here we investigate possible improvements in image reconstruction for BCT, by optimizing free regularization parameter in method of maximum likelihood and comparing its performance with clinical cone-beam filtered backprojection (FBP) algorithm.
C1 [Makeev, Andrey; Glick, Stephen J.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Imaging Diagnost & Software Reliabil, Silver Spring, MD 20993 USA.
[Ikejimba, Lynda; Lo, Joseph Y.] Duke Univ, Dept Radiol, Med Phys Grad Program, Carl E Ravin Adv Imaging Labs, Durham, NC 27708 USA.
[Lo, Joseph Y.] Duke Univ, Dept Biomed Engn, Dept Elect & Comp Engn, Durham, NC 27708 USA.
RP Makeev, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Imaging Diagnost & Software Reliabil, Silver Spring, MD 20993 USA.
EM andrey.makeev@fda.hhs.gov
NR 5
TC 0
Z9 0
U1 0
U2 0
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-5106-0018-8
J9 PROC SPIE
PY 2016
VL 9783
AR 978327
DI 10.1117/12.2217438
PG 7
WC Optics; Physics, Multidisciplinary; Radiology, Nuclear Medicine &
Medical Imaging
SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging
GA BE9YS
UT WOS:000378352900074
ER
PT S
AU Maurino, SL
Badano, A
Cunningham, IA
Karim, KS
AF Maurino, Sebastian Lopez
Badano, Aldo
Cunningham, Ian A.
Karim, Karim S.
BE Kontos, D
Flohr, TG
Lo, JY
TI Theoretical and Monte Carlo optimization of a stacked three-layer
flat-panel x-ray imager for applications in multi-spectral diagnostic
medical imaging
SO MEDICAL IMAGING 2016: PHYSICS OF MEDICAL IMAGING
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Medical Imaging - Physics of Medical Imaging
CY FEB 28-MAR 02, 2016
CL San Diego, CA
SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD, Carestream Hlth Inc, GE Healthcare
DE Dual Energy; X-ray; Diagnosis; Multilayer; Flat-Panel Detector
ID ENERGY CHEST RADIOGRAPHY; SANDWICH DETECTOR; SCINTILLATORS; SYSTEMS;
NOISE; PERFORMANCE; NODULES
AB We propose a new design of a stacked three-layer flat-panel x-ray detector for dual-energy (DE) imaging. Each layer consists of its own scintillator of individual thickness and an underlying thin-film-transistor-based flat-panel. Three images are obtained simultaneously in the detector during the same x-ray exposure, thereby eliminating any motion artifacts. The detector operation is two-fold: a conventional radiography image can be obtained by combining all three layers' images, while a DE subtraction image can be obtained from the front and back layers' images, where the middle layer acts as a mid-filter that helps achieve spectral separation. We proceed to optimize the detector parameters for two sample imaging tasks that could particularly benefit from this new detector by obtaining the best possible signal to noise ratio per root entrance exposure using well-established theoretical models adapted to fit our new design. These results are compared to a conventional DE temporal subtraction detector and a single-shot DE subtraction detector with a copper mid-filter, both of which underwent the same theoretical optimization. The findings are then validated using advanced Monte Carlo simulations for all optimized detector setups. Given the performance expected from initial results and the recent decrease in price for digital x-ray detectors, the simplicity of the three-layer stacked imager approach appears promising to usher in a new generation of multi-spectral digital x-ray diagnostics.
C1 [Maurino, Sebastian Lopez; Karim, Karim S.] Univ Waterloo, Elect & Comp Engn, Waterloo, ON N2L 3G1, Canada.
[Badano, Aldo] US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
[Cunningham, Ian A.] Univ Western Ontario, Robarts Res Inst, Imaging Res Labs, London, ON N6A 5B7, Canada.
[Cunningham, Ian A.] Univ Western Ontario, Dept Med Biophys, London, ON N6A 5B7, Canada.
[Karim, Karim S.] Univ Waterloo, Ctr Bioengn & Biotechnol, Waterloo, ON N2L 3G1, Canada.
RP Maurino, SL; Karim, KS (reprint author), Univ Waterloo, Elect & Comp Engn, Waterloo, ON N2L 3G1, Canada.; Karim, KS (reprint author), Univ Waterloo, Ctr Bioengn & Biotechnol, Waterloo, ON N2L 3G1, Canada.
EM slopezma@uwaterloo.ca; kkarim@uwaterloo.ca
OI badano, aldo/0000-0003-3712-6670
NR 42
TC 0
Z9 0
U1 1
U2 1
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-5106-0018-8
J9 PROC SPIE
PY 2016
VL 9783
AR 97833Z
DI 10.1117/12.2217085
PG 14
WC Optics; Physics, Multidisciplinary; Radiology, Nuclear Medicine &
Medical Imaging
SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging
GA BE9YS
UT WOS:000378352900137
ER
PT S
AU Popescu, LM
AF Popescu, Lucretiu M.
BE Kontos, D
Flohr, TG
Lo, JY
TI Hybrid deterministic and stochastic X-ray transport simulation for
transmission computed tomography with advanced detector noise model
SO MEDICAL IMAGING 2016: PHYSICS OF MEDICAL IMAGING
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Medical Imaging - Physics of Medical Imaging
CY FEB 28-MAR 02, 2016
CL San Diego, CA
SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD, Carestream Hlth Inc, GE Healthcare
ID PULSE-HEIGHT SPECTROSCOPY; SYSTEM
AB We present a model for simulation of noisy X-ray computed tomography data sets. The model is made of two main components, a photon transport simulation component that generates the noiseless photon field incident on the detector, and a detector response model that takes as input the incident photon field parameters and given the X-ray source intensity and exposure time can generate noisy data sets, accordingly. The photon transport simulation component combines direct ray-tracing of polychromatic X-rays for calculation of transmitted data, with Monte Carlo simulation for calculation of the scattered-photon data. The Monte Carlo scatter simulation is accelerated by implementing particle splitting and importance sampling variance reduction techniques. The detector-incident photon field data are stored as energy expansion coefficients on a refined grid that covers the detector area. From these data the detector response model is able to generate noisy detector data realizations, by reconstituting the main parameters that describe each detector element response in statistical terms, including spatial correlations. The model is able to generate very fast, on the fly, CT data sets corresponding to different radiation doses, as well as detector response characteristics, facilitating data management in extensive optimization studies by reducing the computation time and storage space demands.
C1 [Popescu, Lucretiu M.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
RP Popescu, LM (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM lucretiu.popescu@fda.hhs.gov
NR 13
TC 0
Z9 0
U1 0
U2 1
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-5106-0018-8
J9 PROC SPIE
PY 2016
VL 9783
AR 97833H
DI 10.1117/12.2217281
PG 10
WC Optics; Physics, Multidisciplinary; Radiology, Nuclear Medicine &
Medical Imaging
SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging
GA BE9YS
UT WOS:000378352900119
ER
PT S
AU Sikaria, D
Musinksy, S
Sturgeon, GM
Solomon, J
Diao, A
Gehm, ME
Samei, E
Glick, SJ
Lo, JY
AF Sikaria, Dhiraj
Musinksy, Stephanie
Sturgeon, Gregory M.
Solomon, Justin
Diao, Andrew
Gehm, Michael E.
Samei, Ehsan
Glick, Stephen J.
Lo, Joseph Y.
BE Kontos, D
Flohr, TG
Lo, JY
TI Second generation anthropomorphic physical phantom for mammography and
DBT: Incorporating voxelized 3D printing and inkjet printing of
iodinated lesion inserts
SO MEDICAL IMAGING 2016: PHYSICS OF MEDICAL IMAGING
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Medical Imaging - Physics of Medical Imaging
CY FEB 28-MAR 02, 2016
CL San Diego, CA
SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD, Carestream Hlth Inc, GE Healthcare
DE Mammography; digital breast tomosynthesis; phantom design; phantom
evaluation; 3D printing; image quality; x-ray imaging; quality control
ID BREAST PHANTOM
AB Physical phantoms are needed for the evaluation and optimization of new digital breast tomosynthesis (DBT) systems. Previously, we developed an anthropomorphic phantom based on human subject breast CT data and fabricated using commercial 3D printing. We now present three key advancements: voxelized 3D printing, photopolymer material doping, and 2D inkjet printing of lesion inserts. First, we bypassed the printer's control software in order to print in voxelized form instead of conventional STL surfaces, thus improving resolution and allowing dithering to mix the two photopolymer materials into arbitrary proportions. We demonstrated ability to print details as small as 150 mu m, and dithering to combine VeroWhitePlus and TangoPlus in 10% increments. Second, to address the limited attenuation difference among commercial photopolymers, we evaluated a beta sample from Stratasys with increased TiO2 doping concentration up to 2.5%, which corresponded to 98% breast density. By spanning 36% to 98% breast density, this doubles our previous contrast. Third, using inkjet printers modified to print with iopamidol, we created 2D lesion patterns on paper that can be sandwiched into the phantom. Inkjet printing has advantages of being inexpensive and easy, and more contrast can be delivered through overprinting. Printing resolution was maintained at 210 lam horizontally and 330 lam vertically even after 10 overprints. Contrast increased linearly with overprinting at 0.7% per overprint. Together, these three new features provide the basis for creating a new anthropomorphic physical breast phantom with improved resolution and contrast, as well as the ability to insert 2D lesions for task-based assessment of performance.
C1 [Sikaria, Dhiraj; Musinksy, Stephanie; Samei, Ehsan; Lo, Joseph Y.] Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA.
[Diao, Andrew; Gehm, Michael E.; Samei, Ehsan; Lo, Joseph Y.] Duke Univ, Dept Elect & Comp Engn, Durham, NC USA.
[Sikaria, Dhiraj; Musinksy, Stephanie; Sturgeon, Gregory M.; Solomon, Justin; Samei, Ehsan; Lo, Joseph Y.] Duke Univ, Sch Med, Dept Radiol, Carl E Ravin Adv Imaging Labs, Durham, NC USA.
[Solomon, Justin; Samei, Ehsan; Lo, Joseph Y.] Duke Univ, Med Phys Grad Program, Durham, NC 27706 USA.
[Glick, Stephen J.] US FDA, Div Imaging Diagnost & Software Reliabil, OSEL, CDRH, Rockville, MD 20857 USA.
[Samei, Ehsan] Duke Univ, Dept Phys, Durham, NC 27706 USA.
RP Sikaria, D (reprint author), Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA.; Sikaria, D (reprint author), Duke Univ, Sch Med, Dept Radiol, Carl E Ravin Adv Imaging Labs, Durham, NC USA.
NR 6
TC 1
Z9 1
U1 3
U2 3
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-5106-0018-8
J9 PROC SPIE
PY 2016
VL 9783
AR 978360
DI 10.1117/12.2217667
PG 10
WC Optics; Physics, Multidisciplinary; Radiology, Nuclear Medicine &
Medical Imaging
SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging
GA BE9YS
UT WOS:000378352900202
ER
PT S
AU Sturgeon, GM
Tward, DJ
Ketcha, M
Ratnanather, JT
Miller, MI
Park, S
Segars, WP
Lo, JY
AF Sturgeon, Gregory M.
Tward, Daniel J.
Ketcha, M.
Ratnanather, J. T.
Miller, M. I.
Park, Subok
Segars, W. P.
Lo, Joseph Y.
BE Kontos, D
Flohr, TG
Lo, JY
TI Eigenbreasts for Statistical Breast Phantoms
SO MEDICAL IMAGING 2016: PHYSICS OF MEDICAL IMAGING
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Medical Imaging - Physics of Medical Imaging
CY FEB 28-MAR 02, 2016
CL San Diego, CA
SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD, Carestream Hlth Inc, GE Healthcare
DE Eigenbreasts; statistical breast phantoms; computational phantom;
virtual clinical trials; model observer; breast imaging
AB To facilitate rigorous virtual clinical trials using model observers for breast imaging optimization and evaluation, we demonstrated a method of defining statistical models, based on 177 sets of breast CT patient data, in order to generate tens of thousands of unique digital breast phantoms.
In order to separate anatomical texture from variation in breast shape, each training set of breast phantoms were deformed to a consistent atlas compressed geometry. Principal component analysis (PCA) was then performed on the shape-matched breast CT volumes to capture the variation of patient breast textures. PCA decomposes the training set of N breast CT volumes into an N-1-dimensional space of eigenvectors, which we call eigenbreasts. By summing weighted combinations of eigenbreasts, a large ensemble of different breast phantoms can be newly created.
Different training sets can be used in eigenbreast analysis for designing basis models to target sub-populations defined by breast characteristics, such as size or density. In this work, we plan to generate ensembles of 30,000 new phantoms based on glandularity for an upcoming virtual trial of lesion detectability in digital breast tomosynthesis.
Our method extends our series of digital and physical breast phantoms based on human subject anatomy, providing the capability to generate new, unique ensembles consisting of tens of thousands or more virtual subjects. This work represents an important step towards conducting future virtual trials for tasks-based assessment of breast imaging, where it is vital to have a large ensemble of realistic phantoms for statistical power as well as clinical relevance.
C1 [Sturgeon, Gregory M.; Segars, W. P.; Lo, Joseph Y.] Duke Univ, Med Ctr, Dept Radiol, Carl E Ravin Adv Imaging Labs, Durham, NC 27710 USA.
[Tward, Daniel J.; Ketcha, M.; Ratnanather, J. T.; Miller, M. I.] Johns Hopkins Univ, Ctr Imaging Sci, Baltimore, MD USA.
[Park, Subok] OSEL CDRH FDA, Div Imaging Diagnost & Software Reliabil, White Oak, MD USA.
RP Sturgeon, GM (reprint author), Duke Univ, Med Ctr, Dept Radiol, Carl E Ravin Adv Imaging Labs, Durham, NC 27710 USA.
NR 12
TC 0
Z9 0
U1 0
U2 0
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-5106-0018-8
J9 PROC SPIE
PY 2016
VL 9783
AR 97832B
DI 10.1117/12.2216398
PG 9
WC Optics; Physics, Multidisciplinary; Radiology, Nuclear Medicine &
Medical Imaging
SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging
GA BE9YS
UT WOS:000378352900078
ER
PT S
AU Hassan, M
Ilev, IK
AF Hassan, Moinuddin
Ilev, Ilko K.
BE Gannot, I
TI Fiber-optic Fourier transform infrared (FO-FTIR) spectroscopy for
detecting endotoxin contamination in ophthalmic viscosurgical devices
(OVDS) (Conference Presentation)
SO OPTICAL FIBERS AND SENSORS FOR MEDICAL DIAGNOSTICS AND TREATMENT
APPLICATIONS XVI
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Optical Fibers and Sensors for Medical Diagnostics and
Treatment Applications XVI
CY FEB 13-14, 2016
CL San Francisco, CA
SP SPIE
C1 [Hassan, Moinuddin; Ilev, Ilko K.] US FDA, Rockville, MD 20857 USA.
RP Hassan, M (reprint author), US FDA, Rockville, MD 20857 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-62841-936-8
J9 PROC SPIE
PY 2016
VL 9702
AR 970204
DI 10.1117/12.2219746
PG 1
WC Remote Sensing; Optics; Radiology, Nuclear Medicine & Medical Imaging
SC Remote Sensing; Optics; Radiology, Nuclear Medicine & Medical Imaging
GA BE9RZ
UT WOS:000378117400003
ER
PT S
AU Ilev, IK
Walker, B
Calhoun, W
Hassan, M
AF Ilev, Ilko K.
Walker, Bennett
Calhoun, William
Hassan, Moinuddin
BE Gannot, I
TI Advanced biosensing methodologies developed for evaluating performance
quality and safety of emerging biophotonics technologies and medical
devices (Conference Presentation)
SO OPTICAL FIBERS AND SENSORS FOR MEDICAL DIAGNOSTICS AND TREATMENT
APPLICATIONS XVI
SE Proceedings of SPIE
LA English
DT Proceedings Paper
CT Conference on Optical Fibers and Sensors for Medical Diagnostics and
Treatment Applications XVI
CY FEB 13-14, 2016
CL San Francisco, CA
SP SPIE
C1 [Ilev, Ilko K.; Walker, Bennett; Calhoun, William; Hassan, Moinuddin] US FDA, Rockville, MD 20857 USA.
RP Ilev, IK (reprint author), US FDA, Rockville, MD 20857 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPIE-INT SOC OPTICAL ENGINEERING
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA
SN 0277-786X
BN 978-1-62841-936-8
J9 PROC SPIE
PY 2016
VL 9702
AR 97020O
DI 10.1117/12.2220083
PG 1
WC Remote Sensing; Optics; Radiology, Nuclear Medicine & Medical Imaging
SC Remote Sensing; Optics; Radiology, Nuclear Medicine & Medical Imaging
GA BE9RZ
UT WOS:000378117400020
ER
PT J
AU Dmitrienko, A
Kordzakhia, G
Brechenmacher, T
AF Dmitrienko, Alex
Kordzakhia, George
Brechenmacher, Thomas
TI Mixture-based gatekeeping procedures for multiplicity problems with
multiple sequences of hypotheses
SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS
LA English
DT Article
DE Clinical trials; closed testing; gatekeeping procedure; mixture method;
multiple testing
ID CLINICAL-TRIAL APPLICATIONS; ADJUSTMENT METHODS; TESTING PROCEDURES;
MULTISTAGE
AB Complex multiplicity problems arise in drug development programs with several sets of clinical objectives. This article considers a common setting with two sources of multiplicity induced by the analysis of multiple dose levels based on ordered endpoints. This results in multiplicity problems with multiple sequences of null hypotheses of no effect. Type I error rate inflation in problems of this type is typically addressed by using gatekeeping procedures that account for the hierarchical structure of the trial objectives. A general method for building gatekeeping procedures, known as the mixture method, tends to be conservative in problems with several sequences of hypotheses. This article defines a modified mixture method and shows that this method provides a power advantage over the standard mixture method. In addition, it is demonstrated that in special cases the modified mixture method allows for a stepwise testing algorithm, which facilities the implementation of gatekeeping procedures and general decision making. The new methodology is illustrated using two clinical trial examples.
C1 [Dmitrienko, Alex] Ctr Stat Drug Dev, Quintiles Innovat, 12121 Beverly St, Overland Pk, KS 66209 USA.
[Kordzakhia, George] US FDA, Silver Spring, MD USA.
[Brechenmacher, Thomas] Novartis, Paris, France.
RP Dmitrienko, A (reprint author), Ctr Stat Drug Dev, Quintiles Innovat, 12121 Beverly St, Overland Pk, KS 66209 USA.
EM Alex.Dmitrienko@gmail.com
NR 20
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1054-3406
EI 1520-5711
J9 J BIOPHARM STAT
JI J. Biopharm. Stat.
PY 2016
VL 26
IS 4
BP 758
EP 780
DI 10.1080/10543406.2015.1074917
PG 23
WC Pharmacology & Pharmacy; Statistics & Probability
SC Pharmacology & Pharmacy; Mathematics
GA DN5GY
UT WOS:000377095800012
PM 26247744
ER
PT S
AU Chumakov, KM
AF Chumakov, Konstantin M.
BE Martin, J
TI Methods to Monitor Molecular Consistency of Oral Polio Vaccine
SO POLIOVIRUS: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Reversion to virulence; Quality control of Oral Polio Vaccine;
Quantitative analysis of mutations; PCR; Deep-sequencing
ID NONCODING REGION; NEUROVIRULENCE; PCR; QUANTITATION; TEMPERATURE;
MUTATIONS; REVERSION; MUTANTS; ASSAY
AB Replication of viruses leads to emergence of mutations and their content in viral populations can increase by selection depending on growth conditions. Some of these mutations have deleterious effect on vaccine safety, such as neurovirulent reversions in the 5'-UTR of attenuated Sabin strains of poliovirus. Their content in vaccine batches must be tightly controlled during vaccine manufacture to ensure safety of the product. This chapter describes a quantitative molecular procedure called mutant analysis by PCR and restriction enzyme cleavage (MAPREC) that is used to monitor content of neurovirulent revertants in Oral Polio Vaccine (OPV). The method can be used for quantitative analysis of any other mutation in a viral population.
C1 [Chumakov, Konstantin M.] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
RP Chumakov, KM (reprint author), US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
NR 14
TC 0
Z9 0
U1 1
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-4939-3292-4; 978-1-4939-3291-7
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2016
VL 1387
BP 263
EP 277
DI 10.1007/978-1-4939-3292-4_14
D2 10.1007/978-1-4939-3292-4
PG 15
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Infectious Diseases; Medical Laboratory Technology; Virology
SC Biochemistry & Molecular Biology; Infectious Diseases; Medical
Laboratory Technology; Virology
GA BE8LQ
UT WOS:000376577800015
PM 26983740
ER
PT J
AU Rahardja, D
Wu, H
Huang, SG
Chu, JX
AF Rahardja, Dewi
Wu, Han
Huang, Shuguang
Chu, Jianxiong
TI Confidence intervals for the odds ratio of two independent binomial
proportions using data with one type of misclassification
SO JOURNAL OF STATISTICS & MANAGEMENT SYSTEMS
LA English
DT Article
DE Odds ratio; Identifiability; Binary data; False positive
misclassification
ID FALSE-POSITIVE MISCLASSIFICATION; DOUBLE SAMPLING SCHEME; BINARY DATA;
BAYESIAN-APPROACH; SUBJECT
AB We derive a confidence interval for the odd ratio of two independent binomial proportion parameters with one type of misclassification using an easy-to-implement closed-form algorithm based on the Maximum Likelihood Estimator (MLE) and its asymptotic variance. The model identifiability is obtained via doubly sampled data. For illustration, we apply our methods to a sudden infant death syndrome (SIDS) dataset.
C1 [Rahardja, Dewi] US Dept Def, Ft George G Meade, MD 20755 USA.
[Wu, Han] Mankato State Univ, Dept Math & Stat, Mankato, MN 56001 USA.
[Huang, Shuguang] Precis Therapeut Inc, Dept Biostat, Pittsburgh, PA 15203 USA.
[Chu, Jianxiong] US FDA, Silver Spring, MD 20993 USA.
RP Rahardja, D (reprint author), US Dept Def, Ft George G Meade, MD 20755 USA.
EM rahardja@gmail.com
NR 14
TC 0
Z9 0
U1 1
U2 1
PU TARU PUBLICATIONS
PI NEW DELHI
PA G-159, PUSHKAR ENCLAVE, PASHCHIM VIHAR, NEW DELHI, 110 063, INDIA
SN 0972-0510
EI 2169-0014
J9 J STAT MANAG SYST
JI J. Stat. Manag. Syst.
PY 2016
VL 19
IS 2
BP 259
EP 268
DI 10.1080/09720510.2015.1047572
PG 10
WC Statistics & Probability
SC Mathematics
GA DM7JP
UT WOS:000376536800006
ER
PT J
AU Skorski, MR
Esenther, JM
Ahmed, Z
Miller, AE
Hartings, MR
AF Skorski, Matthew R.
Esenther, Jake M.
Ahmed, Zeeshan
Miller, Abigail E.
Hartings, Matthew R.
TI The chemical, mechanical, and physical properties of 3D printed
materials composed of TiO2-ABS nanocomposites
SO SCIENCE AND TECHNOLOGY OF ADVANCED MATERIALS
LA English
DT Article
DE 3D printing; nanocomposite; TiO2 nanoparticle; ABS; photocatalysis
ID NANOPARTICLES; REACTIONWARE; WATER; PHOTOCATALYSIS; PURIFICATION;
DEPENDENCE; STABILITY; SHAPE
AB To expand the chemical capabilities of 3D printed structures generated from commercial thermoplastic printers, we have produced and printed polymer filaments that contain inorganic nanoparticles. TiO2 was dispersed into acrylonitrile butadiene styrene (ABS) and extruded into filaments with 1.75 mm diameters. We produced filaments with TiO2 compositions of 1, 5, and 10% (kg/kg) and printed structures using a commercial 3D printer. Our experiments suggest that ABS undergoes minor degradation in the presence of TiO2 during the different processing steps. The measured mechanical properties (strain and Young's modulus) for all of the composites are similar to those of structures printed from the pure polymer. TiO2 incorporation at 1% negatively affects the stress at breaking point and the flexural stress. Structures produced from the 5 and 10% nanocomposites display a higher breaking point stress than those printed from the pure polymer. TiO2 within the printed matrix was able to quench the intrinsic fluorescence of the polymer. TiO2 was also able to photocatalyze the degradation of a rhodamine 6G in solution. These experiments display chemical reactivity in nanocomposites that are printed using commercial 3D printers, and we expect that our methodology will help to inform others who seek to incorporate catalytic nanoparticles in 3D printed structures.
C1 [Skorski, Matthew R.; Esenther, Jake M.; Miller, Abigail E.; Hartings, Matthew R.] Amer Univ, Dept Chem, 4400 Massachusetts Ave NW, Washington, DC 20016 USA.
[Ahmed, Zeeshan] NIST, Thermodynam Metrol Grp, Sensor Sci Div, Phys Measurement Lab, Gaithersburg, MD 20899 USA.
[Miller, Abigail E.] US FDA, Washington, DC 20204 USA.
RP Skorski, MR (reprint author), Amer Univ, Dept Chem, 4400 Massachusetts Ave NW, Washington, DC 20016 USA.
EM hartings@american.edu
FU Intramural NIST DOC [9999-NIST]
NR 33
TC 1
Z9 1
U1 26
U2 43
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1468-6996
EI 1878-5514
J9 SCI TECHNOL ADV MAT
JI Sci. Technol. Adv. Mater.
PY 2016
VL 17
IS 1
BP 89
EP 97
DI 10.1080/14686996.2016.1152879
PG 9
WC Materials Science, Multidisciplinary
SC Materials Science
GA DM7AD
UT WOS:000376503300012
PM 27375367
ER
PT J
AU Chockalingam, AK
Hamed, S
Goodwin, DG
Rosenzweig, BA
Pang, E
Boyne, MT
Patel, V
AF Chockalingam, Ashok K.
Hamed, Salaheldin
Goodwin, David G.
Rosenzweig, Barry A.
Pang, Eric
Boyne, Michael T., II
Patel, Vikram
TI The Effect of Oseltamivir on the Disease Progression of Lethal Influenza
A Virus Infection: Plasma Cytokine and miRNA Responses in a Mouse Model
SO DISEASE MARKERS
LA English
DT Article
ID NEURAMINIDASE INHIBITOR OSELTAMIVIR; HIGHLY PATHOGENIC H5N1; MICRORNA
EXPRESSION; MICE; MORTALITY; VIRULENCE; SERUM; LUNG; H1N1
AB Lethal influenza A virus infection leads to acute lung injury and possibly lethal complications. There has been a continuous effort to identify the possible predictors of disease severity. Unlike earlier studies, where biomarkers were analyzed on certain time points or days after infection, in this study biomarkers were evaluated over the entire course of infection. Circulating proinflammatory cytokines and/or miRNAs that track with the onset and progression of lethal A/Puerto Rico/8/34 (PR8) influenza A virus infection and their response to oseltamivir treatment were investigated up to 10 days after infection. Changes in plasma cytokines (IL-1 beta., IL-10, IL-12p70, IL-6, KC, TNF-alpha, and IFN-gamma) and several candidate miRNAs were profiled. Among the cytokines analyzed, IL-6 and KC/GRO cytokines appeared to correlate with peak viral titer. Over the selected 48 miRNAs profiled, certain miRNAs were up-or downregulated in a manner that was dependent on the oseltamivir treatment and disease severity. Our findings suggest that IL-6 and KC/GRO cytokines can be a potential disease severity biomarker and/or marker for the progression/remission of infection. Further studies to explore other cytokines, miRNAs, and lung injury proteins in serum with different subtypes of influenza A viruses with varying disease severity may provide new insight into other unique biomarkers.
C1 [Chockalingam, Ashok K.; Rosenzweig, Barry A.; Patel, Vikram] US FDA, DARS, OCP, OTS,CDER, Silver Spring, MD 20993 USA.
[Hamed, Salaheldin] US FDA, OCP, OTS, CDER, Silver Spring, MD 20993 USA.
[Goodwin, David G.] US FDA, DMD, OIR, CDRH, Silver Spring, MD 20993 USA.
[Pang, Eric] US FDA, OPQ, OLDP, CDER, Silver Spring, MD 20993 USA.
[Boyne, Michael T., II] US FDA, DPA, OTR, OPS,CDER, Silver Spring, MD 20993 USA.
RP Patel, V (reprint author), US FDA, DARS, OCP, OTS,CDER, Silver Spring, MD 20993 USA.
EM vikram.patel@fda.hhs.gov
FU Medical Countermeasures Initiative (MCMi), Center for Drug Evaluation
and Research (CDER), US Food and Drug Administration
FX This project received funding from Medical Countermeasures Initiative
(MCMi), Center for Drug Evaluation and Research (CDER), US Food and Drug
Administration. The authors thank Dr. Karol Thompson, Division of
Applied Regulatory Science (CDER), US FDA, for her valuable input for
the miRNA arrays and for critically reading the paper.
NR 34
TC 0
Z9 0
U1 2
U2 4
PU HINDAWI PUBLISHING CORP
PI NEW YORK
PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA
SN 0278-0240
EI 1875-8630
J9 DIS MARKERS
JI Dis. Markers
PY 2016
AR 9296457
DI 10.1155/2016/9296457
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental; Pathology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine; Pathology
GA DJ7VC
UT WOS:000374420200001
ER
PT J
AU Todorov, TI
Gray, PJ
AF Todorov, Todor I.
Gray, Patrick J.
TI Analysis of iodine in food samples by inductively coupled plasma-mass
spectrometry
SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL
EXPOSURE & RISK ASSESSMENT
LA English
DT Article
DE Iodine; ICP-MS; alkaline extraction; carbon addition; validation;
reference materials
ID VALIDATION; COMBUSTION; PRODUCTS; SYSTEM; MILK
AB This work shows a method for the determination of iodine in a variety of food samples and reference materials using inductively coupled plasma-mass spectrometry (ICP-MS) following alkaline extraction. Optimisation of the addition of organic carbon showed that a minimum of 3% 2-propanol was necessary for a constant ratio of iodine to internal standard. The limit of quantification (LOQ), calculated as 30 sigma for the method, was 36 ng g(-1) in solid food samples. For method validation, seven standard reference materials (SRM) and 21 fortified food samples were used. The precision (%RSD) of the measurements was in the 2-7% range. Accuracies for the SRMs were 85-105%, while the fortified food samples showed 81-119% recoveries, including a number of samples fortified at 50% of the LOQ.
C1 [Todorov, Todor I.; Gray, Patrick J.] US Food & Drug Adm, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
RP Todorov, TI (reprint author), US Food & Drug Adm, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
EM todor.todorov@fda.hhs.gov
OI Gray, Patrick/0000-0002-8248-2749
NR 32
TC 1
Z9 1
U1 5
U2 10
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1944-0049
EI 1944-0057
J9 FOOD ADDIT CONTAM A
JI Food Addit. Contam. Part A-Chem.
PY 2016
VL 33
IS 2
BP 282
EP 290
DI 10.1080/19440049.2015.1131337
PG 9
WC Chemistry, Applied; Food Science & Technology; Toxicology
SC Chemistry; Food Science & Technology; Toxicology
GA DK0HS
UT WOS:000374594200012
PM 26730958
ER
PT J
AU Vaclavikova, M
Paseiro-Cerrato, R
Vaclavik, L
Noonan, GO
DeVries, J
Begley, TH
AF Vaclavikova, Marta
Paseiro-Cerrato, Rafael
Vaclavik, Lukas
Noonan, Gregory O.
DeVries, Jonathan
Begley, Timothy H.
TI Target and non-target analysis of migrants from PVC-coated cans using
UHPLC-Q-Orbitrap MS: evaluation of long-term migration testing
SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL
EXPOSURE & RISK ASSESSMENT
LA English
DT Article
DE PVC; food cans; plasticisers; cross linking agent; benzoguanamine;
migration; UHPLC-HRMS
ID EPOXIDIZED SOYBEAN OIL; CHROMATOGRAPHY-MASS SPECTROMETRY; RAPID
IDENTIFICATION; PLANT TOXINS; LID GASKETS; FOOD; PLASTICIZERS; ADDITIVES
AB A simple, rapid and sensitive method for analyzing multi-target and non-target additives in polyvinyl chloride (PVC) food can coatings using ultra-high-performance liquid chromatography coupled to quadrupole-orbital ion-trap mass spectrometry was developed. This procedure was used to study the behaviour of a cross-linking agent, benzoguanamine (BGA), two slip agents, oleamide and erucamide, and 18 other commonly used plasticisers including phthalates, adipates, sebacates, acetyl tributyl citrate and epoxidised soybean or linseed oils. This optimised method was used to detect these analytes in food simulants (water and 3% acetic acid) in a long-term migration test of PVC-coated food cans for a period ranging from 1 day to 1.5 years at 40 degrees C. Although very low detection limits (5 ng ml(-1)) were obtained for the majority of compounds, none of the monitored plasticisers and slip agents was detected in simulants extracted from cans over the period of the test. However, the presence of BGA in both aqueous food simulants was confirmed based on high-resolution mass spectrometry, product ion spectra and analysis of a reference standard. The BGA concentration in both simulants continued to increase with storage time: after 1.5 years storage in aqueous food simulants at 40 degrees C, BGA was detected at concentrations up to 84 mu g dm(-2). We believe this is the first study describing the long-term migration capacity of BGA from any vinyl coating material intended for use in PVC-coated food cans. Our results may have implications for migration test protocols for food cans that will be stored for extended time periods.
C1 [Vaclavikova, Marta; Paseiro-Cerrato, Rafael; Vaclavik, Lukas; Noonan, Gregory O.; Begley, Timothy H.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
[DeVries, Jonathan] DeVries Associates, Coon Rapids, MN USA.
RP Vaclavikova, M (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM marta.vaclavikova1@gmail.com
NR 26
TC 1
Z9 1
U1 5
U2 16
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1944-0049
EI 1944-0057
J9 FOOD ADDIT CONTAM A
JI Food Addit. Contam. Part A-Chem.
PY 2016
VL 33
IS 2
BP 352
EP 363
DI 10.1080/19440049.2015.1128564
PG 12
WC Chemistry, Applied; Food Science & Technology; Toxicology
SC Chemistry; Food Science & Technology; Toxicology
GA DK0HS
UT WOS:000374594200019
PM 26744815
ER
PT J
AU Genualdi, S
MacMahon, S
Robbins, K
Farris, S
Shyong, N
DeJager, L
AF Genualdi, Susie
MacMahon, Shaun
Robbins, Katherine
Farris, Samantha
Shyong, Nicole
DeJager, Lowri
TI Method development and survey of Sudan I-IV in palm oil and chilli
spices in the Washington, DC, area
SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL
EXPOSURE & RISK ASSESSMENT
LA English
DT Article
DE Sudan dyes; palm oil; colour additive; LC-MS/MS; LC-DAD
ID CONTAINING FOODSTUFFS; ARRAY DETECTION; DYES
AB Sudan I, II, III and IV dyes are banned for use as food colorants in the United States and European Union because they are toxic and carcinogenic. These dyes have been illegally used as food additives in products such as chilli spices and palm oil to enhance their red colour. From 2003 to 2005, the European Union made a series of decisions requiring chilli spices and palm oil imported to the European Union to contain analytical reports declaring them free of Sudan I-IV. In order for the USFDA to investigate the adulteration of palm oil and chilli spices with unapproved colour additives in the United States, a method was developed for the extraction and analysis of Sudan dyes in palm oil, and previous methods were validated for Sudan dyes in chilli spices. Both LC-DAD and LC-MS/MS methods were examined for their limitations and effectiveness in identifying adulterated samples. Method validation was performed for both chilli spices and palm oil by spiking samples known to be free of Sudan dyes at concentrations close to the limit of detection. Reproducibility, matrix effects, and selectivity of the method were also investigated. Additionally, for the first time a survey of palm oil and chilli spices was performed in the United States, specifically in the Washington, DC, area. Illegal dyes, primarily Sudan IV, were detected in palm oil at concentrations from 150 to 24 000 ng ml(-1). Low concentrations (< 21 mu g kg(-1)) of Sudan dyes were found in 11 out of 57 spices and are most likely a result of cross-contamination during preparation and storage and not intentional adulteration.
C1 [Genualdi, Susie; MacMahon, Shaun; Robbins, Katherine; Farris, Samantha; Shyong, Nicole; DeJager, Lowri] US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
RP Genualdi, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM susan.genualdi@fda.hhs.gov
FU Intramural FDA HHS [FD999999]
NR 20
TC 0
Z9 0
U1 4
U2 7
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1944-0049
EI 1944-0057
J9 FOOD ADDIT CONTAM A
JI Food Addit. Contam. Part A-Chem.
PY 2016
VL 33
IS 4
BP 583
EP 591
DI 10.1080/19440049.2016.1147986
PG 9
WC Chemistry, Applied; Food Science & Technology; Toxicology
SC Chemistry; Food Science & Technology; Toxicology
GA DK0HT
UT WOS:000374594400001
PM 26824489
ER
PT J
AU Peddareddygari, LR
Hanna, PA
Igo, RP
Luo, YQA
Won, S
Hirano, M
Grewal, RP
AF Peddareddygari, Leema Reddy
Hanna, Philip A.
Igo, Robert P., Jr.
Luo, Yuqun A.
Won, Sungho
Hirano, Michio
Grewal, Raji P.
TI Autosomal dominant hereditary spastic paraplegia with axonal sensory
motor polyneuropathy maps to chromosome 21q 22.3
SO INTERNATIONAL JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE hereditary spastic paraplegia; clinical and genetic analysis; autosomal
dominant; family-based linkage analysis; fine mapping; candidate gene
analysis
AB Aim: Hereditary spastic paraplegia (HSP) are a genetically and clinically heterogeneous group of disorders. At present, 19 autosomal dominant loci for HSP have been mapped. We ascertained an American family of European descent segregating an autosomal dominant HSP associated with peripheral neuropathy. Methods: A genome wide scan was performed with 410 microsatellite repeat marker (Weber lab screening set 16) and following linkage and haplotype analysis, fine mapping was performed. Established genes or loci for HSP were excluded by direct sequencing or haplotype analysis. Results: All established loci for HSP were excluded. Fine mapping suggested a locus on chromosome 21q22.3 flanked by markers D21S1411 and D21S1446 with a maximum logarithm of odds score of 2.05 and was supported by haplotype analysis. A number of candidate genes in this region were analyzed and no disease-producing mutations were detected. Conclusion: We present the clinical and genetic analysis of an American family with autosomal dominant HSP with axonal sensory motor polyneuropathy mapping to a novel locus on chromosome 21q22.3 designated SPG56.
C1 [Peddareddygari, Leema Reddy] Neurogenet Inst, Sharon Hill, PA USA.
[Hanna, Philip A.] JFK Med Ctr, New Jersey Neurosci Inst, Edison, NJ USA.
[Igo, Robert P., Jr.; Luo, Yuqun A.; Won, Sungho] Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Luo, Yuqun A.] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MA USA.
[Won, Sungho] Seoul Natl Univ, Grad Sch Publ Hlth, Seoul, South Korea.
[Hirano, Michio] Columbia Univ, Dept Neurol, New York, NY USA.
[Grewal, Raji P.] St Francis Med Ctr, Inst Neurosci, Trenton, NJ USA.
RP Grewal, RP (reprint author), Seton Hall Univ, St Francis Med Ctr, Neurosci, 601 Hamilton Ave, Trenton, NJ USA.
EM RGrewal@stfrancismedical.org
FU Neurogenetics Foundation, Cranbury, NJ, USA; Neurogenetics Institute,
Sharon Hill, PA, USA
FX The authors report no conflicts of interest. The authors alone are
responsible for the content and writing of the paper. We acknowledge
support from the Neurogenetics Foundation, Cranbury, NJ, USA and the
Neurogenetics Institute, Sharon Hill, PA, USA.
NR 6
TC 0
Z9 0
U1 0
U2 2
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 0020-7454
EI 1563-5279
J9 INT J NEUROSCI
JI Int. J. Neurosci.
PY 2016
VL 126
IS 7
BP 600
EP 606
DI 10.3109/00207454.2015.1048805
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA DL4QY
UT WOS:000375623500005
PM 26000935
ER
PT J
AU Tegegn, TZ
De Paoli, SH
Orecna, M
Elhelu, OK
Woodle, SA
Tarandovskiy, ID
Ovanesov, MV
Simak, J
AF Tegegn, Tseday Z.
De Paoli, Silvia H.
Orecna, Martina
Elhelu, Oumsalama K.
Woodle, Samuel A.
Tarandovskiy, Ivan D.
Ovanesov, Mikhail V.
Simak, Jan
TI Characterization of procoagulant extracellular vesicles and platelet
membrane disintegration in DMSO-cryopreserved platelets
SO JOURNAL OF EXTRACELLULAR VESICLES
LA English
DT Article
DE extracellular vesicles; microparticles; platelet physiology; blood
products; thrombin; transfusion medicine; nanoparticle tracking
analysis; flow cytometry; atomic force microscopy; electron microscopy
ID NANOPARTICLE TRACKING ANALYSIS; PERCENT DIMETHYL-SULFOXIDE; MULTICOLOR
FLOW-CYTOMETRY; FREEZING HUMAN PLATELETS; FROZEN HUMAN PLATELETS; HUMAN
BLOOD-PLATELETS; CARBON NANOTUBES; HEMOSTATIC EFFECTIVENESS;
CALCIUM-ENTRY; TISSUE FACTOR
AB Background: Freezing is promising for extended platelet (PLT) storage for transfusion. 6% DMSO cryopreserved PLTs (CPPs) are currently in clinical development. CPPs contain significant amount of platelet membrane vesicles (PMVs). PLT-membrane changes and PMV release in CPP are poorly understood, and haemostatic effects of CPP PMVs are not fully elucidated. This study aims to investigate PLT-membrane alterations in CPPs and provide comprehensive characterization of CPP PMVs, and their contribution to procoagulant activity (PCA) of CPPs.
Methods: CPPs and corresponding liquid-stored PLTs (LSPs) were characterized by flow cytometry (FC), fluorescence polarization (FP), nanoparticle tracking analysis (NTA), electron microscopy (SEM, TEM), atomic force microscopy (AFM) and thrombin-generation (TG) test.
Results: SEM and TEM revealed disintegration and vesiculation of the PLT-plasma membrane and loss of intracellular organization in 60% PLTs in CPPs. FP demonstrated that 6% DMSO alone and with freezing-thawing caused marked increase in PLT-membrane fluidity. The FC counts of annexin V-binding PMVs and CD41a(+) PMVs were 68-and 56-folds higher, respectively, in CPPs than in LSPs. The AFM and NTA size distribution of PMVs in CPPs indicated a peak diameter of 100 nm, corresponding to exosome-size vesicles. TG-based PCA of CPPs was 2- and 9-folds higher per PLT and per volume, respectively, compared to LSPs. Differential centrifugation showed that CPP supernatant contributed 26% to CPP TG-PCA, mostly by the exosome-size PMVs and their TG-PCA was phosphatidylserine dependent.
Conclusions: Major portion of CPPs does not show activation phenotype but exhibits grape-like membrane disintegration with significant increase of membrane fluidity induced by 6% DMSO alone and further aggravated by freezing-thawing process. DMSO cryopreservation of PLTs is associated with the release of PMVs and marked increase of TG-PCA, as compared to LSPs. Exosome-size PMVs have significant contribution to PCA of CPPs.
C1 [Tegegn, Tseday Z.; De Paoli, Silvia H.; Orecna, Martina; Elhelu, Oumsalama K.; Woodle, Samuel A.; Tarandovskiy, Ivan D.; Ovanesov, Mikhail V.; Simak, Jan] US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
RP Simak, J (reprint author), US FDA, Lab Cellular Hematol, DHRR OBRR, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave,WO Bldg 52-72,Rm 4210, Silver Spring, MD 20993 USA.
EM jan.simak@fda.hhs.gov
NR 51
TC 1
Z9 1
U1 6
U2 9
PU CO-ACTION PUBLISHING
PI JARFALLA
PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN
SN 2001-3078
J9 J EXTRACELL VESICLES
JI J. Extracell. Vesicles
PY 2016
VL 5
AR 30422
DI 10.3402/jev.v5.30422
PG 13
WC Cell Biology
SC Cell Biology
GA DL8WE
UT WOS:000375921900001
PM 27151397
ER
PT J
AU Gavrielides, MA
Li, Q
Zeng, RP
Myers, KJ
Sahiner, B
Petrick, N
AF Gavrielides, Marios A.
Li, Qin
Zeng, Rongping
Myers, Kyle J.
Sahiner, Berkman
Petrick, Nicholas
TI Volume estimation of multidensity nodules with thoracic computed
tomography
SO JOURNAL OF MEDICAL IMAGING
LA English
DT Article
DE volume estimation; multidensity nodules; thoracic computed tomography;
phantom study
ID GROUND-GLASS OPACITY; PULMONARY NODULES; SIZE ESTIMATION; CT; PHANTOM;
RECONSTRUCTION
AB This work focuses on volume estimation of "multidensity" lung nodules in a phantom computed tomography study. Eight objects were manufactured by enclosing spherical cores within larger spheres of double the diameter but with a different density. Different combinations of outer-shell/inner-core diameters and densities were created. The nodules were placed within an anthropomorphic phantom and scanned with various acquisition and reconstruction parameters. The volumes of the entire multidensity object as well as the inner core of the object were estimated using a model-based volume estimator. Results showed percent volume bias across all nodules and imaging protocols with slice thicknesses <5 mm ranging from -5.1% to 6.6% for the entire object (standard deviation ranged from 1.5% to 7.6%), and within -12.6% to 5.7% for the inner-core measurement (standard deviation ranged from 2.0% to 17.7%). Overall, the estimation error was larger for the inner-core measurements, which was expected due to the smaller size of the core. Reconstructed slice thickness was found to substantially affect volumetric error for both tasks; exposure and reconstruction kernel were not. These findings provide information for understanding uncertainty in volumetry of nodules that include multiple densities such as ground glass opacities with a solid component. (C) 2016 Society of Photo-Optical Instrumentation Engineers (SPIE)
C1 [Gavrielides, Marios A.; Li, Qin; Zeng, Rongping; Myers, Kyle J.; Sahiner, Berkman; Petrick, Nicholas] US FDA, DIDSR, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Room 4126, Silver Spring, MD 20993 USA.
RP Gavrielides, MA (reprint author), US FDA, DIDSR, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Room 4126, Silver Spring, MD 20993 USA.
EM marios.gavrielides@fda.hhs.gov
NR 18
TC 0
Z9 0
U1 1
U2 3
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 2329-4302
EI 2329-4310
J9 J MED IMAGING
JI J. Med. Imaging
PD JAN-MAR
PY 2016
VL 3
IS 1
AR 013504
DI 10.1117/1.JMI.3.1.013504
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DJ5HA
UT WOS:000374236300015
PM 26844235
ER
PT J
AU Asher, DM
Gregori, L
Serer, A
McDowell, KL
AF Asher, David M.
Gregori, Luisa
Serer, Arthur
McDowell, Kristy L.
TI Rapid testing for Creutzfeldt-Jakob disease in donors of human tissues
SO PRION
LA English
DT Meeting Abstract
C1 [Asher, David M.; Gregori, Luisa; Serer, Arthur; McDowell, Kristy L.] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1933-6896
EI 1933-690X
J9 PRION
JI Prion
PY 2016
VL 10
SU 1
MA P-123
BP S99
EP S100
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DK1EW
UT WOS:000374656300141
ER
PT J
AU Yang, H
Huang, Y
Bui-Klimke, T
Gregori, L
Asher, DM
Forshee, RA
Anderson, SA
AF Yang, Hong
Huang, Yin
Bui-Klimke, Travis
Gregori, Luisa
Asher, David M.
Forshee, Richard A.
Anderson, Steven A.
TI Geographic risk of variant Creutzfeldt-Jakob disease: A risk ranking
model to evaluate options for blood donor deferral policies in the US
SO PRION
LA English
DT Meeting Abstract
C1 [Yang, Hong; Huang, Yin; Gregori, Luisa; Forshee, Richard A.; Anderson, Steven A.] US FDA, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1933-6896
EI 1933-690X
J9 PRION
JI Prion
PY 2016
VL 10
SU 1
MA P-126
BP S101
EP S102
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DK1EW
UT WOS:000374656300144
ER
PT J
AU Goktas, H
Wang, XX
Boscher, ND
Torosian, S
Gleason, KK
AF Goktas, Hilal
Wang, Xiaoxue
Boscher, Nicolas D.
Torosian, Stephen
Gleason, Karen K.
TI Functionalizable and electrically conductive thin films formed by
oxidative chemical vapor deposition (oCVD) from mixtures of
3-thiopheneethanol (3TE) and ethylene dioxythiophene (EDOT)
SO JOURNAL OF MATERIALS CHEMISTRY C
LA English
DT Article
ID POLYMER-COVERED ELECTRODES; POLY(3,4-ETHYLENEDIOXYTHIOPHENE) FILMS;
CONJUGATED POLYMERS; REACTIVE GROUPS; SOLAR-CELLS; DERIVATIVES;
ELECTROPOLYMERIZATION; TRANSPARENT; SIGNATURES; BIOSENSOR
AB Mixtures of 3-thiopheneethanol (3TE) and 3,4-ethylenedioxythiophene (EDOT) were used as the reactants for oxidative chemical vapor deposition (oCVD). Monomer (3TE : EDOT) feed ratios of (3 : 1), (3 : 2), (3 : 3), (2 : 3), and (1 : 3) were employed to obtain conductive polymer thin films with varying densities of hydroxyl pendant groups. The incorporation of both 3TE and EDOT units into the deposited films was confirmed by a combination of high resolution mass spectrometry, UV-visible-Near Infrared (UV-vis-NIR), and Fourier transform infrared (FTIR) spectroscopy, yielding conductive and -OH functionalized thin films. Theoretical analysis of the initial formation of dimers was studied by using density functional theory (DFT). The calculation predicts that the reaction of 3TE and EDOT is kinetically favored over the combination of two 3TE monomers. The pi-pi* transition observed at 425 nm in the UV-vis-NIR spectra of the 3TE polymerized film red shifts with increasing EDOT incorporation. This transition is observed at 523 nm in the film prepared using (1 : 3) a monomer feed ratio.
C1 [Goktas, Hilal; Wang, Xiaoxue; Boscher, Nicolas D.; Gleason, Karen K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
[Goktas, Hilal; Torosian, Stephen] US FDA, Winchester Engn & Analyt Ctr, 109 Holton St, Winchester, MA 01890 USA.
[Boscher, Nicolas D.] Luxembourg Inst Sci & Technol, Mat Res & Technol Dept, 5 Ave Hauts Fourneaux, L-4362 Luxembourg, Luxembourg.
RP Gleason, KK (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
EM kkg@mit.edu
RI Gleason, Karen/G-1471-2013
OI Gleason, Karen/0000-0001-6127-1056
FU FDA ORISE Fellowship
FX Hilal Goktas, on-leave from Physics Department of Canakkale Onsekiz Mart
University, was supported by the FDA ORISE Fellowship. N. D. B. is
particularly grateful to the Fonds National de la Recherche (FNR) of
Luxembourg for supporting his visiting scientist position within the
Gleason group (SENSi project). N. Desbenoit and G. Frache from LIST are
acknowledged for acquisition of the mass-spectrometry measurements.
NR 45
TC 1
Z9 1
U1 5
U2 7
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 2050-7526
EI 2050-7534
J9 J MATER CHEM C
JI J. Mater. Chem. C
PY 2016
VL 4
IS 16
BP 3403
EP 3414
DI 10.1039/c6tc00567e
PG 12
WC Materials Science, Multidisciplinary; Physics, Applied
SC Materials Science; Physics
GA DK2ZU
UT WOS:000374785300006
ER
PT J
AU Ma, XM
Zhang, XT
Yang, L
Wang, G
Jiang, K
Wu, G
Cui, WG
Wei, ZP
AF Ma, Xiaoming
Zhang, Xiaoting
Yang, Lin
Wang, Ge
Jiang, Kai
Wu, Geoffrey
Cui, Weigang
Wei, Zipeng
TI Tunable construction of multi-shelled hollow carbonate nanospheres and
their potential applications
SO NANOSCALE
LA English
DT Article
ID LITHIUM-ION BATTERIES; HEAVY-METAL IONS; MESOPOROUS SILICA NANOSPHERES;
AMORPHOUS CALCIUM-CARBONATE; TEMPLATE-FREE SYNTHESIS; SENSITIZED
SOLAR-CELLS; DRUG-DELIVERY; FUNCTIONALIZED CELL; ACCURATE CONTROL;
MICROSPHERES
AB The development of multi-shelled hollow carbonate nanospheres (MHCN) for biomedical applications is challenging, and has not been reported. In this study, a facile approach is firstly reported to synthesize hierarchically porous MHCN with controllable shell numbers using a novel strategy called layer-by-layer thermal decomposition of organic acid salts and templates. The choice of organic acid salts as the reactants is innovative and crucial. The shell numbers of porous MHCN can be easily controlled and tuned through adjusting the adsorption temperature of organic acid salts and/or the adsorption ability of the template. The synthetic method can not only open a window to prepare the multi-shelled carbonates but also provide a new strategy to synthesise other multi-shelled inorganic salts. Notably, the hierarchically porous multi-shelled hollow structures empower the carbonates with not only a large specific surface area but also good porosity and permeability, showing great potential for future applications. Herein, our in vitro/vivo evaluations show that CaCO3 MHCN possess a high drug loading capacity and a sustained-release drug profile. It is highly expected that this novel synthetic strategy for MHCN and novel MHCN platform have the potential for biomedical applications in the near future.
C1 [Ma, Xiaoming; Zhang, Xiaoting; Yang, Lin; Wang, Ge; Jiang, Kai; Wei, Zipeng] Henan Normal Univ, Collaborat Innovat Ctr Henan Prov Green Mfg Fine, Key Lab Green Chem Media & React, Minist Educ,Sch Chem & Chem Engn, Xinxiang 453007, Henan, Peoples R China.
[Wu, Geoffrey] US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
[Cui, Weigang] Xinxiang Med Univ, Dept Human Anat, Xinxiang 453003, Henan, Peoples R China.
RP Ma, XM (reprint author), Henan Normal Univ, Collaborat Innovat Ctr Henan Prov Green Mfg Fine, Key Lab Green Chem Media & React, Minist Educ,Sch Chem & Chem Engn, Xinxiang 453007, Henan, Peoples R China.
EM sunshinyma@hotmail.com
FU National Science Foundation of China [21271065, 21171051]; NFSC-Henan
Talent Training United Fund [U1204519]
FX We thank Professor Xinming Liu (Department of Pharmaceutical Sciences,
College of Pharmacy, the University of Nebraska Medical Center) for
assistance in the characterization studies and the biomedical
applications of the multi-shelled CaCO3. This work was
financially supported by the National Science Foundation of China (Grant
No. 21271065 and No. 21171051) and the NFSC-Henan Talent Training United
Fund (Grant No. U1204519).
NR 46
TC 1
Z9 1
U1 23
U2 51
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 2040-3364
EI 2040-3372
J9 NANOSCALE
JI Nanoscale
PY 2016
VL 8
IS 16
BP 8687
EP 8695
DI 10.1039/c6nr00866f
PG 9
WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials
Science, Multidisciplinary; Physics, Applied
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA DK3BA
UT WOS:000374788800034
PM 27049523
ER
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Chiang, Hui-Ling
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Cho, Dong-Hyung
Cho, Ssang-Goo
Cho, William C.
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Cho, Young-Seok
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Choi, Eui-Ju
Choi, Eun-Kyoung
Choi, Jayoung
Choi, Mary E.
Choi, Seung-Il
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Choubey, Vinay
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Chowdhury, Kamal
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Chuang, Tsung-Hsien
Chun, Taehoon
Chung, Hyewon
Chung, Taijoon
Chung, Yuen-Li
Chwae, Yong-Joon
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Cohen, Ezra E. W.
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Cooper, Cynthia D.
Cooper, J. Mark
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Corral-Ramos, Cristina
Corti, Olga
Cossarizza, Andrea
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Covey, Lori R.
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Cox, Jeffery S.
Coxon, Fraser P.
Coyne, Carolyn B.
Cragg, Mark S.
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Crippa, Valeria
Cruz, Maria Teresa
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Cui, Taixing
Cutillas, Pedro R.
Czaja, Mark J.
Czyzyk-Krzeska, Maria F.
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Dahmen, Uta
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Dai, Wenjie
Dai, Yun
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Valle, Luisa Dalla
Dalmasso, Guillaume
D'Amelio, Marcello
Damme, Markus
Darfeuille-Michaud, Arlette
Dargemont, Catherine
Darley-Usmar, Victor M.
Dasarathy, Srinivasan
Dasgupta, Biplab
Dash, Srikanta
Dass, Crispin R.
Davey, Hazel Marie
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Davila, David
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Daza, Paula
de Belleroche, Jackie
de Figueiredo, Paul
Bressan Queiroz de Figueiredo, Regina Celia
de la Fuente, Jose
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De Meyer, Guido R. Y.
De Milito, Angelo
De Santi, Mauro
de Souza, Wanderley
De Tata, Vincenzo
De Zio, Daniela
Debnath, Jayanta
Dechant, Reinhard
Decuypere, Jean-Paul
Deegan, Shane
Dehay, Benjamin
Del Bello, Barbara
Del Re, Dominic P.
Delage-Mourroux, Regis
Delbridge, Lea M. D.
Deldicque, Louise
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Deng, Yizhen
Dengjel, Joern
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Deretic, Vojo
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DiAntonio, Aaron
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Diaz-Laviada, Ines
Diaz-Meco, Maria T.
Diaz-Nido, Javier
Dickey, Chad A.
Dickson, Robert C.
Diederich, Marc
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Dikic, Ivan
Dinesh-Kumar, Savithrama P.
Ding, Chan
Ding, Wen-Xing
Ding, Zufeng
Dini, Luciana
Distler, Joerg H. W.
Diwan, Abhinav
Djavaheri-Mergny, Mojgan
Dmytruk, Kostyantyn
Dobson, Renwick C. J.
Doetsch, Volker
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Dokudovskaya, Svetlana
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Dong, X. Charlie
Dong, Xiaonan
Dong, Zheng
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Doran, Kelly S.
D'Orazi, Gabriella
Dorn, Gerald W., II
Dosenko, Victor
Dridi, Sami
Drucker, Liat
Du, Jie
Du, Li-Lin
Du, Lihuan
du Toit, Andre
Dua, Priyamvada
Duan, Lei
Duann, Pu
Dubey, Vikash Kumar
Duchen, Michael R.
Duchosal, Michel A.
Duez, Helene
Dugail, Isabelle
Dumit, Veronica I.
Duncan, Mara C.
Dunlop, Elaine A.
Dunn, William A., Jr.
Dupont, Nicolas
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Duvvuri, Umamaheswar
Eapen, Vinay
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Echard, Arnaud
Eckhart, Leopold
Edelstein, Charles L.
Edinger, Aimee L.
Eichinger, Ludwig
Eisenberg, Tobias
Eisenberg-Lerner, Avital
Eissa, N. Tony
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El-Khoury, Victoria
Elazar, Zvulun
Eldar-Finkelman, Hagit
Elliott, Chris J. H.
Emanuele, Enzo
Emmenegger, Urban
Engedal, Nikolai
Engelbrecht, Anna-Mart
Engelender, Simone
Enserink, Jorrit M.
Erdmann, Ralf
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Eri, Rajaraman
Eriksen, Jason L.
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Escalante, Ricardo
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Espert, Lucile
Esteban-Martinez, Lorena
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Fabrizi, Cinzia
Facchiano, Antonio
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Faggioni, Alberto
Fairlie, W. Douglas
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Fan, Daping
Fan, Jie
Fang, Shengyun
Fanto, Manolis
Fanzani, Alessandro
Farkas, Thomas
Faure, Mathias
Favier, Francois B.
Fearnhead, Howard
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Fei, Erkang
Felizardo, Tania C.
Feng, Hua
Feng, Yibin
Feng, Yuchen
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Fernandez, Alvaro F.
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Fernandez-Checa, Jose C.
Fernandez-Lopez, Arsenio
Fernandez-Zapico, Martin E.
Feron, Olivier
Ferraro, Elisabetta
Ferreira-Halder, Carmen Verissima
Fesus, Laszlo
Feuer, Ralph
Fiesel, Fabienne C.
Filippi-Chiela, Eduardo C.
Filomeni, Giuseppe
Fimia, Gian Maria
Fingert, John H.
Finkbeiner, Steven
Finkel, Toren
Fiorito, Filomena
Fisher, Paul B.
Flajolet, Marc
Flamigni, Flavio
Florey, Oliver
Florio, Salvatore
Floto, R. Andres
Folini, Marco
Follo, Carlo
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Fornai, Francesco
Fortunato, Franco
Fraldi, Alessandro
Franco, Rodrigo
Francois, Arnaud
Francois, Aurelie
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Fraser, Iain D. C.
Frey, Norbert
Freyssenet, Damien G.
Frezza, Christian
Friedman, Scott L.
Frigo, Daniel E.
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Fuentes, Jose M.
Fueyo, Juan
Fujitani, Yoshio
Fujiwara, Yuuki
Fujiya, Mikihiro
Fukuda, Mitsunori
Fulda, Simone
Fusco, Carmela
Gabryel, Bozena
Gaestel, Matthias
Gailly, Philippe
Gajewska, Malgorzata
Galadari, Sehamuddin
Galili, Gad
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Galindo, Maria F.
Galliciotti, Giovanna
Galluzzi, Lorenzo
Galluzzi, Luca
Galy, Vincent
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Garcia-Ruiz, Carmen
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Garg, Pramod Kumar
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Gavard, Julie
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Ge, Pengfei
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Girardin, Stephen E.
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Giuliano, Sandy
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Gleave, Martin
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Goping, Ing Swie
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Gorbunov, Nikolai V.
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Greenhough, Alexander
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Grimaldi, Benedetto
Gros, Frederic
Grose, Charles
Groulx, Jean-Francois
Gruber, Florian
Grumati, Paolo
Grune, Tilman
Guan, Jun-Lin
Guan, Kun-Liang
Guerra, Barbara
Guillen, Carlos
Gulshan, Kailash
Gunst, Jan
Guo, Chuanyong
Guo, Lei
Guo, Ming
Guo, Wenjie
Guo, Xu-Guang
Gust, Andrea A.
Gustafsson, Asa B.
Gutierrez, Elaine
Gutierrez, Maximiliano G.
Gwak, Ho-Shin
Haas, Albert
Haber, James E.
Hadano, Shinji
Hagedorn, Monica
Hahn, David R.
Halayko, Andrew J.
Hamacher-Brady, Anne
Hamada, Kozo
Hamai, Ahmed
Hamann, Andrea
Hamasaki, Maho
Hamer, Isabelle
Hamid, Qutayba
Hammond, Ester M.
Han, Feng
Han, Weidong
Handa, James T.
Hanover, John A.
Hansen, Malene
Harada, Masaru
Harhaji-Trajkovic, Ljubica
Harper, J. Wade
Harrath, Abdel Halim
Harris, Adrian L.
Harris, James
Hasler, Udo
Hasselblatt, Peter
Hasui, Kazuhisa
Hawley, Robert G.
Hawley, Teresa S.
He, Congcong
He, Cynthia Y.
He, Fengtian
He, Gu
He, Rong-Rong
He, Xian-Hui
He, You-Wen
He, Yu-Ying
Heath, Joan K.
Hebert, Marie-Josee
Heinzen, Robert A.
Helgason, Gudmundur Vignir
Hensel, Michael
Henske, Elizabeth P.
Her, Chengtao
Herman, Paul K.
Hernandez, Agustin
Hernandez, Carlos
Hernandez-Tiedra, Sonia
Hetz, Claudio
Hiesinger, P. Robin
Higaki, Katsumi
Hilfiker, Sabine
Hill, Bradford G.
Hill, Joseph A.
Hill, William D.
Hino, Keisuke
Hofius, Daniel
Hofman, Paul
Hoeglinger, Guenter U.
Hoehfeld, Joerg
Holz, Marina K.
Hong, Yonggeun
Hood, David A.
Hoozemans, Jeroen J. M.
Hoppe, Thorsten
Hsu, Chin
Hsu, Chin-Yuan
Hsu, Li-Chung
Hu, Dong
Hu, Guochang
Hu, Hong-Ming
Hu, Hongbo
Hu, Ming Chang
Hu, Yu-Chen
Hu, Zhuo-Wei
Hua, Fang
Hua, Ya
Huang, Canhua
Huang, Huey-Lan
Huang, Kuo-How
Huang, Kuo-Yang
Huang, Shile
Huang, Shiqian
Huang, Wei-Pang
Huang, Yi-Ran
Huang, Yong
Huang, Yunfei
Huber, Tobias B.
Huebbe, Patricia
Huh, Won-Ki
Hulmi, Juha J.
Hur, Gang Min
Hurley, James H.
Husak, Zvenyslava
Hussain, Sabah N. A.
Hussain, Salik
Hwang, Jung Jin
Hwang, Seungmin
Hwang, Thomas I. S.
Ichihara, Atsuhiro
Imai, Yuzuru
Imbriano, Carol
Inomata, Megumi
Into, Takeshi
Iovane, Valentina
Iovanna, Juan L.
Iozzo, Renato V.
Ip, Nancy Y.
Irazoqui, Javier E.
Iribarren, Pablo
Isaka, Yoshitaka
Isakovic, Aleksandra J.
Ischiropoulos, Harry
Isenberg, Jeffrey S.
Ishaq, Mohammad
Ishida, Hiroyuki
Ishii, Isao
Ishmael, Jane E.
Isidoro, Ciro
Isobe, Ken-ichi
Isono, Erika
Issazadeh-Navikas, Shohreh
Itahana, Koji
Itakura, Eisuke
Ivanov, Andrei I.
Iyer, Anand Krishnan V.
Izquierdo, Jose M.
Izumi, Yotaro
Izzo, Valentina
Jaeaettelae, Marja
Jaber, Nadia
Jackson, Daniel John
Jackson, William T.
Jacob, Tony George
Jacques, Thomas S.
Jagannath, Chinnaswamy
Jain, Ashish
Jana, Nihar Ranjan
Jang, Byoung Kuk
Jani, Alkesh
Janji, Bassam
Jannig, Paulo Roberto
Jansson, Patric J.
Jean, Steve
Jendrach, Marina
Jeon, Ju-Hong
Jessen, Niels
Jeung, Eui-Bae
Jia, Kailiang
Jia, Lijun
Jiang, Hong
Jiang, Hongchi
Jiang, Liwen
Jiang, Teng
Jiang, Xiaoyan
Jiang, Xuejun
Jiang, Xuejun
Jiang, Ying
Jiang, Yongjun
Jimenez, Alberto
Jin, Cheng
Jin, Hongchuan
Jin, Lei
Jin, Meiyan
Jin, Shengkan
Jinwal, Umesh Kumar
Jo, Eun-Kyeong
Johansen, Terje
Johnson, Daniel E.
Johnson, Gail V. W.
Johnson, James D.
Jonasch, Eric
Jones, Chris
Joosten, Leo A. B.
Jordan, Joaquin
Joseph, Anna-Maria
Joseph, Bertrand
Joubert, Annie M.
Ju, Dianwen
Ju, Jingfang
Juan, Hsueh-Fen
Juenemann, Katrin
Juhasz, Gabor
Jung, Hye Seung
Jung, Jae U.
Jung, Yong-Keun
Jungbluth, Heinz
Justice, Matthew J.
Jutten, Barry
Kaakoush, Nadeem O.
Kaarniranta, Kai
Kaasik, Allen
Kabuta, Tomohiro
Kaeffer, Bertrand
Kagedal, Katarina
Kahana, Alon
Kajimura, Shingo
Kakhlon, Or
Kalia, Manjula
Kalvakolanu, Dhan V.
Kamada, Yoshiaki
Kambas, Konstantinos
Kaminskyy, Vitaliy O.
Kampinga, Harm H.
Kandouz, Mustapha
Kang, Chanhee
Kang, Rui
Kang, Tae-Cheon
Kanki, Tomotake
Kanneganti, Thirumala-Devi
Kanno, Haruo
Kanthasamy, Anumantha G.
Kantorow, Marc
Kaparakis-Liaskos, Maria
Kapuy, Orsolya
Karantza, Vassiliki
Karim, Md Razaul
Karmakar, Parimal
Kaser, Arthur
Kaushik, Susmita
Kawula, Thomas
Kaynar, A. Murat
Ke, Po-Yuan
Ke, Zun-Ji
Kehrl, John H.
Keller, Kate E.
Kemper, Jongsook Kim
Kenworthy, Anne K.
Kepp, Oliver
Kern, Andreas
Kesari, Santosh
Kessel, David
Ketteler, Robin
Kettelhut, Isis do Carmo
Khambu, Bilon
Khan, Muzamil Majid
Khandelwal, Vinoth K. M.
Khare, Sangeeta
Kiang, Juliann G.
Kiger, Amy A.
Kihara, Akio
Kim, Arianna L.
Kim, Cheol Hyeon
Kim, Deok Ryong
Kim, Do-Hyung
Kim, Eung Kweon
Kim, Hye Young
Kim, Hyung-Ryong
Kim, Jae-Sung
Kim, Jeong Hun
Kim, Jin Cheon
Kim, Jin Hyoung
Kim, Kwang Woon
Kim, Michael D.
Kim, Moon-Moo
Kim, Peter K.
Kim, Seong Who
Kim, Soo-Youl
Kim, Yong-Sun
Kim, Yonghyun
Kimchi, Adi
Kimmelman, Alec C.
Kimura, Tomonori
King, Jason S.
Kirkegaard, Karla
Kirkin, Vladimir
Kirshenbaum, Lorrie A.
Kishi, Shuji
Kitajima, Yasuo
Kitamoto, Katsuhiko
Kitaoka, Yasushi
Kitazato, Kaio
Kley, Rudolf A.
Klimecki, Walter T.
Klinkenberg, Michael
Klucken, Jochen
Knaevelsrud, Helene
Knecht, Erwin
Knuppertz, Laura
Ko, Jiunn-Liang
Kobayashi, Satoru
Koch, Jan C.
Koechlin-Ramonatxo, Christelle
Koenig, Ulrich
Ko, Young Ho
Koehler, Katja
Kohlwein, Sepp D.
Koike, Masato
Komatsu, Masaaki
Kominami, Eiki
Kong, Dexin
Kong, Hee Jeong
Konstantakou, Eumorphia G.
Kopp, Benjamin T.
Korcsmaros, Tamas
Korhonen, Laura
Korolchuk, Viktor I.
Koshkina, Nadya V.
Kou, Yanjun
Koukourakis, Michael I.
Koumenis, Constantinos
Kovacs, Attila L.
Kovacs, Tibor
Kovacs, Werner J.
Koya, Daisuke
Kraft, Claudine
Krainc, Dimitri
Kramer, Helmut
Kravic-Stevovic, Tamara
Krek, Wilhelm
Kretz-Remy, Carole
Krick, Roswitha
Krishnamurthy, Malathi
Kriston-Vizi, Janos
Kroemer, Guido
Kruer, Michael C.
Kruger, Rejko
Ktistakis, Nicholas T.
Kuchitsu, Kazuyuki
Kuhn, Christian
Kumar, Addanki Pratap
Kumar, Anuj
Kumar, Ashok
Kumar, Deepak
Kumar, Dhiraj
Kumar, Rakesh
Kumar, Sharad
Kundu, Mondira
Kung, Hsing-Jien
Kuno, Atsushi
Kuo, Sheng-Han
Kuret, Jeff
Kurz, Tino
Kwok, Terry
Kwon, Taeg Kyu
Kwon, Yong Tae
Kyrmizi, Irene
La Spada, Albert R.
Lafont, Frank
Lahm, Tim
Lakkaraju, Aparna
Lam, Truong
Lamark, Trond
Lancel, Steve
Landowski, Terry H.
Lane, Darius J. R.
Lane, Jon D.
Lanzi, Cinzia
Lapaquette, Pierre
Lapierre, Louis R.
Laporte, Jocelyn
Laukkarinen, Johanna
Laurie, Gordon W.
Lavandero, Sergio
Lavie, Lena
LaVoie, Matthew J.
Law, Betty Yuen Kwan
Law, Helen Ka-wai
Law, Kelsey B.
Layfield, Robert
Lazo, Pedro A.
Le Cam, Laurent
Le Roch, Karine G.
Le Stunff, Herve
Leardkamolkarn, Vijittra
Lecuit, Marc
Lee, Byung-Hoon
Lee, Che-Hsin
Lee, Erinna F.
Lee, Gyun Min
Lee, He-Jin
Lee, Hsinyu
Lee, Jae Keun
Lee, Jongdae
Lee, Ju-Hyun
Lee, Jun Hee
Lee, Michael
Lee, Myung-Shik
Lee, Patty J.
Lee, Sam W.
Lee, Seung-Jae
Lee, Shiow-Ju
Lee, Stella Y.
Lee, Sug Hyung
Lee, Sung Sik
Lee, Sung-Joon
Lee, Sunhee
Lee, Ying-Ray
Lee, Yong J.
Lee, Young H.
Leeuwenburgh, Christiaan
Lefort, Sylvain
Legouis, Renaud
Lei, Jinzhi
Lei, Qun-Ying
Leib, David A.
Leibowitz, Gil
Lekli, Istvan
Lemaire, Stephane D.
Lemasters, John J.
Lemberg, Marius K.
Lemoine, Antoinette
Leng, Shuilong
Lenz, Guido
Lenzi, Paola
Lerman, Lilach O.
Barbato, Daniele Lettieri
Leu, Julia I-Ju
Leung, Hing Y.
Levine, Beth
Lewis, Patrick A.
Lezoualc'h, Frank
Li, Chi
Li, Faqiang
Li, Feng-Jun
Li, Jun
Li, Ke
Li, Lian
Li, Min
Li, Min
Li, Qiang
Li, Rui
Li, Sheng
Li, Wei
Li, Wei
Li, Xiaotao
Li, Yumin
Lian, Jiqin
Liang, Chengyu
Liang, Qiangrong
Liao, Yulin
Liberal, Joana
Liberski, Pawel P.
Lie, Pearl
Lieberman, Andrew P.
Lim, Hyunjung Jade
Lim, Kah-Leong
Lim, Kyu
Lima, Raquel T.
Lin, Chang-Shen
Lin, Chiou-Feng
Lin, Fang
Lin, Fangming
Lin, Fu-Cheng
Lin, Kui
Lin, Kwang-Huei
Lin, Pei-Hui
Lin, Tianwei
Lin, Wan-Wan
Lin, Yee-Shin
Lin, Yong
Linden, Rafael
Lindholm, Dan
Lindqvist, Lisa M.
Lingor, Paul
Linkermann, Andreas
Liotta, Lance A.
Lipinski, Marta M.
Lira, Vitor A.
Lisanti, Michael P.
Liton, Paloma B.
Liu, Bo
Liu, Chong
Liu, Chun-Feng
Liu, Fei
Liu, Hung-Jen
Liu, Jianxun
Liu, Jing-Jing
Liu, Jing-Lan
Liu, Ke
Liu, Leyuan
Liu, Liang
Liu, Quentin
Liu, Rong-Yu
Liu, Shiming
Liu, Shuwen
Liu, Wei
Liu, Xian-De
Liu, Xiangguo
Liu, Xiao-Hong
Liu, Xinfeng
Liu, Xu
Liu, Xueqin
Liu, Yang
Liu, Yule
Liu, Zexian
Liu, Zhe
Liuzzi, Juan P.
Lizard, Gerard
Ljujic, Mila
Lodhi, Irfan J.
Logue, Susan E.
Lokeshwar, Bal L.
Long, Yun Chau
Lonial, Sagar
Loos, Benjamin
Lopez-Otin, Carlos
Lopez-Vicario, Cristina
Lorente, Mar
Lorenzi, Philip L.
Lorincz, Peter
Los, Marek
Lotze, Michael T.
Lovat, Penny E.
Lu, Binfeng
Lu, Bo
Lu, Jiahong
Lu, Qing
Lu, She-Min
Lu, Shuyan
Lu, Yingying
Luciano, Federic
Luckhart, Shirley
Lucocq, John Milton
Ludovico, Paula
Lugea, Aurelia
Lukacs, Nicholas W.
Lum, Julian J.
Lund, Anders H.
Luo, Honglin
Luo, Jia
Luo, Shouqing
Luparello, Claudio
Lyons, Timothy
Ma, Jianjie
Ma, Yi
Ma, Yong
Ma, Zhenyi
Machado, Juliano
Machado-Santelli, Glaucia M.
Macian, Fernando
MacIntosh, Gustavo C.
MacKeigan, Jeffrey P.
Macleod, Kay F.
MacMicking, John D.
MacMillan-Crow, Lee Ann
Madeo, Frank
Madesh, Muniswamy
Madrigal-Matute, Julio
Maeda, Akiko
Maeda, Tatsuya
Maegawa, Gustavo
Maellaro, Emilia
Maes, Hannelore
Magarinos, Marta
Maiese, Kenneth
Maiti, Tapas K.
Maiuri, Luigi
Maiuri, Maria Chiara
Maki, Carl G.
Malli, Roland
Malorni, Walter
Maloyan, Alina
Mami-Chouaib, Fathia
Man, Na
Mancias, Joseph D.
Mandelkow, Eva-Maria
Mandell, Michael A.
Manfredi, Angelo A.
Manie, Serge N.
Manzoni, Claudia
Mao, Kai
Mao, Zixu
Mao, Zong-Wan
Marambaud, Philippe
Marconi, Anna Maria
Marelja, Zvonimir
Marfe, Gabriella
Margeta, Marta
Margittai, Eva
Mari, Muriel
Mariani, Francesca V.
Marin, Concepcio
Marinelli, Sara
Marino, Guillermo
Markovic, Ivanka
Marquez, Rebecca
Martelli, Alberto M.
Martens, Sascha
Martin, Katie R.
Martin, Seamus J.
Martin, Shaun
Martin-Acebes, Miguel A.
Martin-Sanz, Paloma
Martinand-Mari, Camille
Martinet, Wim
Martinez, Jennifer
Martinez-Lopez, Nuria
Martinez-Outschoorn, Ubaldo
Martinez-Velazquez, Moises
Martinez-Vicente, Marta
Martins, Waleska Kerllen
Mashima, Hirosato
Mastrianni, James A.
Matarese, Giuseppe
Matarrese, Paola
Mateo, Roberto
Matoba, Satoaki
Matsumoto, Naomichi
Matsushita, Takehiko
Matsuura, Akira
Matsuzawa, Takeshi
Mattson, Mark P.
Matus, Soledad
Maugeri, Norma
Mauvezin, Caroline
Mayer, Andreas
Maysinger, Dusica
Mazzolini, Guillermo D.
McBrayer, Mary Kate
McCall, Kimberly
McCormick, Craig
McInerney, Gerald M.
McIver, Skye C.
McKenna, Sharon
McMahon, John J.
McNeish, Iain A.
Mechta-Grigoriou, Fatima
Medema, Jan Paul
Medina, Diego L.
Megyeri, Klara
Mehrpour, Maryam
Mehta, Jawahar L.
Mei, Yide
Meier, Ute-Christiane
Meijer, Alfred J.
Melendez, Alicia
Melino, Gerry
Melino, Sonia
Tenorio de Melo, Edesio Jose
Mena, Maria A.
Meneghini, Marc D.
Menendez, Javier A.
Menezes, Regina
Meng, Liesu
Meng, Ling-hua
Meng, Songshu
Menghini, Rossella
Menko, A. Sue
Menna-Barreto, Rubem F. S.
Menon, Manoj B.
Meraz-Rios, Marco A.
Merla, Giuseppe
Merlini, Luciano
Merlot, Angelica M.
Meryk, Andreas
Meschini, Stefania
Meyer, Joel N.
Mi, Man-Tian
Miao, Chao-Yu
Micale, Lucia
Michaeli, Simon
Michiels, Carine
Migliaccio, Anna Rita
Mihailidou, Anastasia Susie
Mijaljica, Dalibor
Mikoshiba, Katsuhiko
Milan, Enrico
Miller-Fleming, Leonor
Mills, Gordon B.
Mills, Ian G.
Minakaki, Georgia
Minassian, Berge A.
Ming, Xiu-Fen
Minibayeva, Farida
Minina, Elena A.
Mintern, Justine D.
Minucci, Saverio
Miranda-Vizuete, Antonio
Mitchell, Claire H.
Miyamoto, Shigeki
Miyazawa, Keisuke
Mizushima, Noboru
Mnich, Katarzyna
Mograbi, Baharia
Mohseni, Simin
Moita, Luis Ferreira
Molinari, Marco
Molinari, Maurizio
Moller, Andreas Buch
Mollereau, Bertrand
Mollinedo, Faustino
Monick, Martha M.
Monick, Martha M.
Montagnaro, Serena
Montell, Craig
Moore, Darren J.
Moore, Michael N.
Mora-Rodriguez, Rodrigo
Moreira, Paula I.
Morel, Etienne
Morelli, Maria Beatrice
Moreno, Sandra
Morgan, Michael J.
Moris, Arnaud
Moriyasu, Yuji
Morrison, Janna L.
Morrison, Lynda A.
Morselli, Eugenia
Moscat, Jorge
Moseley, Pope L.
Mostowy, Serge
Motori, Elisa
Mottet, Denis
Mottram, Jeremy C.
Moussa, Charbel E-H
Mpakou, Vassiliki E.
Mukhtar, Hasan
Levy, Jean M. Mulcahy
Muller, Sylviane
Munoz-Moreno, Raquel
Munoz-Pinedo, Cristina
Muenz, Christian
Murphy, Maureen E.
Murray, James T.
Murthy, Aditya
Mysorekar, Indira U.
Nabi, Ivan R.
Nabissi, Massimo
Nader, Gustavo A.
Nagahara, Yukitoshi
Nagai, Yoshitaka
Nagata, Kazuhiro
Nagelkerke, Anika
Nagy, Peter
Naidu, Samisubbu R.
Nair, Sreejayan
Nakano, Hiroyasu
Nakatogawa, Hitoshi
Nanjundan, Meera
Napolitano, Gennaro
Naqvi, Naweed I.
Nardacci, Roberta
Narendra, Derek P.
Narita, Masashi
Nascimbeni, Anna Chiara
Natarajan, Ramesh
Navegantes, Luiz C.
Nawrocki, Steffan T.
Nazarko, Taras Y.
Nazarko, Volodymyr Y.
Neill, Thomas
Neri, Luca M.
Netea, Mihai G.
Netea-Maier, Romana T.
Neves, Bruno M.
Ney, Paul A.
Nezis, Ioannis P.
Nguyen, Hang T. T.
Huu Phuc Nguyen
Nicot, Anne-Sophie
Nilsen, Hilde
Nilsson, Per
Nishimura, Mikio
Nishino, Ichizo
Niso-Santano, Mireia
Niu, Hua
Nixon, Ralph A.
Njar, Vincent C. O.
Noda, Takeshi
Noegel, Angelika A.
Nolte, Elsie Magdalena
Norberg, Erik
Norga, Koenraad K.
Noureini, Sakineh Kazemi
Notomi, Shoji
Notterpek, Lucia
Nowikovsky, Karin
Nukina, Nobuyuki
Nuernberger, Thorsten
O'Donnell, Valerie B.
O'Donovan, Tracey
O'Dwyer, Peter J.
Oehme, Ina
Oeste, Clara L.
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Ogretmen, Besim
Ogura, Yuji
Oh, Young J.
Ohmuraya, Masaki
Ohshima, Takayuki
Ojha, Rani
Okamoto, Koji
Okazaki, Toshiro
Oliver, F. Javier
Ollinger, Karin
Olsson, Stefan
Orban, Daniel P.
Ordonez, Paulina
Orhon, Idil
Orosz, Laszlo
O'Rourke, Eyleen J.
Orozco, Helena
Ortega, Angel L.
Ortona, Elena
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Oshima, Junko
Oshima, Shigeru
Osiewacz, Heinz D.
Otomo, Takanobu
Otsu, Kinya
Ou, Jing-hsiung James
Outeiro, Tiago F.
Ouyang, Dong-yun
Ouyang, Hongjiao
Overholtzer, Michael
Ozbun, Michelle A.
Ozdinler, P. Hande
Ozpolat, Bulent
Pacelli, Consiglia
Paganetti, Paolo
Page, Guylene
Pages, Gilles
Pagnini, Ugo
Pajak, Beata
Pak, Stephen C.
Pakos-Zebrucka, Karolina
Pakpour, Nazzy
Palkova, Zdena
Palladino, Francesca
Pallauf, Kathrin
Pallet, Nicolas
Palmieri, Marta
Paludan, Soren R.
Palumbo, Camilla
Palumbo, Silvia
Pampliega, Olatz
Pan, Hongming
Pan, Wei
Panaretakis, Theocharis
Pandey, Aseem
Pantazopoulou, Areti
Papackova, Zuzana
Papademetrio, Daniela L.
Papassideri, Issidora
Papini, Alessio
Parajuli, Nirmala
Pardo, Julian
Parekh, Vrajesh V.
Parenti, Giancarlo
Park, Jong-In
Park, Junsoo
Park, Ohkmae K.
Parker, Roy
Parlato, Rosanna
Parys, Jan B.
Parzych, Katherine R.
Pasquet, Jean-Max
Pasquier, Benoit
Pasumarthi, Kishore B. S.
Patschan, Daniel
Patterson, Cam
Pattingre, Sophie
Pattison, Scott
Pause, Arnim
Pavenstaedt, Hermann
Pavone, Flaminia
Pedrozo, Zully
Pena, Fernando J.
Penalva, Miguel A.
Pende, Mario
Peng, Jianxin
Penna, Fabio
Penninger, Josef M.
Pensalfini, Anna
Pepe, Salvatore
Pereira, Gustavo J. S.
Pereira, Paulo C.
Perez-de la Cruz, Veronica
Esther Perez-Perez, Maria
Perez-Rodriguez, Diego
Perez-Sala, Dolores
Perier, Celine
Perl, Andras
Perlmutter, David H.
Perrotta, Ida
Pervaiz, Shazib
Pesonen, Maija
Pessin, Jeffrey E.
Peters, Godefridus J.
Petersen, Morten
Petrache, Irina
Petrof, Basil J.
Petrovski, Goran
Phang, James M.
Piacentini, Mauro
Pierdominici, Marina
Pierre, Philippe
Pierrefite-Carle, Valerie
Pietrocola, Federico
Pimentel-Muinos, Felipe X.
Pinar, Mario
Pineda, Benjamin
Pinkas-Kramarski, Ronit
Pinti, Marcello
Pinton, Paolo
Piperdi, Bilal
Piret, James M.
Platanias, Leonidas C.
Platta, Harald W.
Plowey, Edward D.
Poggeler, Stefanie
Poirot, Marc
Polcic, Peter
Poletti, Angelo
Poon, Audrey H.
Popelka, Hana
Popova, Blagovesta
Poprawa, Izabela
Poulose, Shibu M.
Poulton, Joanna
Powers, Scott K.
Powers, Ted
Pozuelo-Rubio, Mercedes
Prak, Krisna
Prange, Reinhild
Prescott, Mark
Priault, Muriel
Prince, Sharon
Proia, Richard L.
Proikas-Cezanne, Tassula
Prokisch, Holger
Promponas, Vasilis J.
Przyklenk, Karin
Puertollano, Rosa
Pugazhenthi, Subbiah
Puglielli, Luigi
Pujol, Aurora
Puyal, Julien
Pyeon, Dohun
Qi, Xin
Qian, Wen-bin
Qin, Zheng-Hong
Qiu, Yu
Qu, Ziwei
Quadrilatero, Joe
Quinn, Frederick
Raben, Nina
Rabinowich, Hannah
Radogna, Flavia
Ragusa, Michael J.
Rahmani, Mohamed
Raina, Komal
Ramanadham, Sasanka
Ramesh, Rajagopal
Rami, Abdelhaq
Randall-Demllo, Sarron
Randow, Felix
Rao, Hai
Rao, V. Ashutosh
Rasmussen, Blake B.
Rasse, Tobias M.
Ratovitski, Edward A.
Rautou, Pierre-Emmanuel
Ray, Swapan K.
Razani, Babak
Reed, Bruce H.
Reggiori, Fulvio
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Reichert, Andreas S.
Rein, Theo
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Reits, Eric
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Ren, Xingcong
Renna, Maurizio
Reusch, Jane E. B.
Revuelta, Jose L.
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Rezaie, Alireza R.
Richards, Robert I.
Richardson, Des R.
Richetta, Clemence
Riehle, Michael A.
Rihn, Bertrand H.
Rikihisa, Yasuko
Riley, Brigit E.
Rimbach, Gerald
Rippo, Maria Rita
Ritis, Konstantinos
Rizzi, Federica
Rizzo, Elizete
Roach, Peter J.
Robbins, Jeffrey
Roberge, Michel
Roca, Gabriela
Roccheri, Maria Carmela
Rocha, Sonia
Rodrigues, Cecilia M. P.
Rodriguez, Clara I.
Rodriguez de Cordoba, Santiago
Rodriguez-Muela, Natalia
Roelofs, Jeroen
Rogov, Vladimir V.
Rohn, Troy T.
Rohrer, Baerbel
Romanelli, Davide
Romani, Luigina
Silvia Romano, Patricia
Roncero, M. Isabel G.
Luis Rosa, Jose
Rosello, Alicia
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Rosenstiel, Philip
Rost-Roszkowska, Magdalena
Roth, Kevin A.
Roue, Gael
Rouis, Mustapha
Rouschop, Kasper M.
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Ruano, Diego
Rubinsztein, David C.
Rucker, Edmund B., III
Rudich, Assaf
Rudolf, Emil
Rudolf, Ruediger
Ruegg, Markus A.
Ruiz-Roldan, Carmen
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Rusmini, Paola
Russ, David W.
Russo, Gian Luigi
Russo, Giuseppe
Russo, Rossella
Rusten, Tor Erik
Ryabovol, Victoria
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Ryter, Stefan W.
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Sacher, Michael
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Sakakura, Koichi
Sakoh-Nakatogawa, Machiko
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Salvaterra, Paul M.
Salvioli, Rosa
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Sanchez-Alcazar, Jose A.
Sanchez-Prieto, Ricardo
Sandri, Marco
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Santaguida, Stefano
Santambrogio, Laura
Santoni, Giorgio
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Saran, Shweta
Sardiello, Marco
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Sarkar, Pallabi
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Sarwal, Minnie M.
Sasakawa, Chihiro
Sasaki, Motoko
Sass, Miklos
Sato, Ken
Sato, Miyuki
Satriano, Joseph
Savaraj, Niramol
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Scharl, Michael
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Schekman, Randy
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Zhang, Yunjiao
Zhao, Mei
Zhao, Wei-Li
Zhao, Xiaonan
Zhao, Yan G.
Zhao, Ying
Zhao, Yongchao
Zhao, Yu-Xia
Zhao, Zhendong
Zhao, Zhizhuang J.
Zheng, Dexian
Zheng, Xi-Long
Zheng, Xiaoxiang
Zhivotovsky, Boris
Zhong, Qing
Zhou, Guang-Zhou
Zhou, Guofei
Zhou, Huiping
Zhou, Shu-Feng
Zhou, Xu-Jie
Zhu, Hongxin
Zhu, Hua
Zhu, Wei-Guo
Zhu, Wenhua
Zhu, Xiao-Feng
Zhu, Yuhua
Zhuang, Shi-Mei
Zhuang, Xiaohong
Ziparo, Elio
Zois, Christos E.
Zoladek, Teresa
Zong, Wei-Xing
Zorzano, Antonio
Zughaier, Susu M.
TI Guidelines for the use and interpretation of assays for monitoring
autophagy (3rd edition)
SO AUTOPHAGY
LA English
DT Review
DE autolysosome; autophagosome; chaperone-mediated autophagy; flux; LC3;
lysosome; macroautophagy; phagophore; stress; vacuole
ID CHAPERONE-MEDIATED AUTOPHAGY; ACTIVATED PROTEIN-KINASE; PROGRAMMED
CELL-DEATH; STARVATION-INDUCED AUTOPHAGY; ENDOPLASMIC-RETICULUM STRESS;
NF-KAPPA-B; VACUOLE TARGETING PATHWAY; ISOLATED RAT HEPATOCYTES; YEAST
SACCHAROMYCES-CEREVISIAE; GLUCAGON-INDUCED AUTOPHAGY
C1 [Tan, Yee-Joo; Zeng, Qi] ASTAR, Inst Mol & Cell Biol, Singapore, Singapore.
[Bagniewska-Zadworna, Agnieszka] Adam Mickiewicz Univ, Dept Gen Bot, Inst Expt Biol, Fac Biol, Poznan, Poland.
[Vendelbo, Mikkel Holm] Aarhus Univ Hosp, Dept Nucl Med, DK-8000 Aarhus, Denmark.
[Vendelbo, Mikkel Holm] PET Ctr, Aarhus, Denmark.
[Paludan, Soren R.] Aarhus Univ, Dept Biomed, Aarhus, Denmark.
[Jessen, Niels] Aarhus Univ, Dept Clin Med, Aarhus, Denmark.
[Andersen, Stig U.] Aarhus Univ, Dept Mol Biol & Genet, Aarhus, Denmark.
[Moller, Andreas Buch] Aarhus Univ, Med Res Lab, Inst Clin Med, Aarhus, Denmark.
[Davey, Hazel Marie] Alberystwyth Univ, Inst Biol Environm & Rural Sci, Aberystwyth, Dyfed, Wales.
[Chen, Guang-Chao; Yang, Wei Yuan] Acad Sinica, Inst Biol Chem, Taipei 115, Taiwan.
[Chen, Steve S-L] Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan.
[Shen, C-K James; Wang, Ting-Fang; Yao, Meng-Chao] Acad Sinica, Inst Mol Biol, Taipei 115, Taiwan.
[van den Brink, Gijs R.; Wildenberg, Manon E.] Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol & Hepatol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
[Reits, Eric] Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
[Graba, Yacine] Aix Marseille Univ, CNRS, IBDM, UMR 7288, Campus Luminy, Marseille, France.
[Ghigo, Eric] Aix Marseille Univ, CNRS, IRD198, UMR 7278,INSERM U1095,Med Fac, Marseille, France.
[Gatti, Evelina; Pierre, Philippe] Aix Marseille Univ, U2M, Ctr Immunol Marseille Luminy, Marseille, France.
[Baek, Seung-Hoon] Ajou Univ, Coll Pharm, Gyeonggido, South Korea.
[Chwae, Yong-Joon] Ajou Univ, Sch Med, Dept Microbiol, Gyeonggi Do, South Korea.
[Nilsen, Hilde] Akershus Univ Hosp, Oslo, Norway.
[Mashima, Hirosato] Akita Univ, Grad Sch Med, Akita 010, Japan.
[Galadari, Sehamuddin] Al Jalila Fdn Res Ctr, Dubai, U Arab Emirates.
[Huang, Yunfei] Albany Med Coll, Ctr Neuropharmacol & Neurosci, Albany, NY 12208 USA.
[Holz, Marina K.] Albert Einstein Canc Ctr, New York, NY USA.
[Cai, Dongsheng; Singh, Rajat] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Coletto, Luisa; Kaushik, Susmita; Madrigal-Matute, Julio] Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10467 USA.
[Arias, Esperanza; Bejarano, Eloy; Cuervo, Ana Maria; Pampliega, Olatz; Schneider, Jaime L.; Tasset-Cuevas, Inmaculada; Villarroya, Joan] Albert Einstein Coll Med, Dept Dev & Mol Biol, Inst Aging Studies, Bronx, NY 10467 USA.
[Czaja, Mark J.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.
[Backer, Jonathan M.] Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10467 USA.
[Macian, Fernando] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA.
[Gavathiotis, Evripidis] Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10467 USA.
[Gavathiotis, Evripidis; Martinez-Lopez, Nuria; Pessin, Jeffrey E.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.
[Garcia-Macia, Marina] Albert Einstein Coll Med, Dept Med Endocrinol, Bronx, NY 10467 USA.
[Garcia-Macia, Marina; Martinez-Lopez, Nuria; Pessin, Jeffrey E.] Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10467 USA.
[Santambrogio, Laura] Albert Einstein Coll Med, Dept Pathol, New York, NY USA.
[Santambrogio, Laura] Albert Einstein Coll Med, Dept Microbiol & Immunol, New York, NY USA.
[Piperdi, Bilal] Albert Einstein Coll Med, Montefiore Med Ctr, Bronx, NY 10467 USA.
[Huber, Tobias B.] Univ Freiburg, Div Renal, Hugstetter Str 55, D-79106 Freiburg, Germany.
[Jacob, Tony George] All India Inst Med Sci, Dept Anat, New Delhi 110029, India.
[Garg, Pramod Kumar] All India Inst Med Sci, Dept Gastroenterol, New Delhi, India.
[Ghosh, Debabrata] All India Inst Med Sci, Dept Physiol, New Delhi, India.
[Lu, Qing] Brown Univ, Alpert Med Sch, Vasc Res Lab, Providence Vet Affairs Med Ctr,Dept Med, Providence, RI 02912 USA.
[Shin, Dong Wook] Amorepacif Corp RandD Ctr, Biosci Res Inst, Gyeonggi, South Korea.
[Hu, Dong] Anhui Univ Sci & Technol, Dept Immunol & Med Inspect, Huainan, Anhui, Peoples R China.
[Song, Chunjuan] Appl Genet Technol Corp, Alachua, FL USA.
[Takemura, Genzou] Asahi Univ, Dept Internal Med, Gifu, Japan.
[Inomata, Megumi; Into, Takeshi] Asahi Univ, Sch Dent, Dept Oral Microbiol, Div Oral Infect & Hlth Sci, Gifu, Japan.
[Fujiya, Mikihiro] Asahikawa Med Univ, Div Gastroenterol & Hematol Oncol, Dept Med, Sapporo, Hokkaido, Japan.
[Hwang, Jung Jin] Asan Inst Life Sci, Asan Med Ctr, Seoul, South Korea.
[Wan, Lei] Asia Univ, Dept Biotechnol, Taichung, Taiwan.
[Beck, George R., Jr.] Vet Affairs Med Ctr, Atlanta Dept, Decatur, GA 30033 USA.
[Mazzolini, Guillermo D.] Austral Univ CONICET, Gene & Cell Therapy Lab, Buenos Aires, DF, Argentina.
[Vila, Miquel] Autonomous Univ Barcelona, Dept Biochem & Mol Biol, Barcelona, Spain.
[Ktistakis, Nicholas T.] Babraham Inst, Cambridge, England.
[Florey, Oliver] Babraham Inst, Signalling Program, Cambridge, England.
[Woodcock, Elizabeth A.] Baker IDI Heart & Diabet Inst, Mol Cardiol Lab, Melbourne, Vic, Australia.
[Eissa, N. Tony] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
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[Chin, Lih-Shen; Li, Lian; She, Hua] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA.
[Anania, Frank A.] Emory Univ, Sch Med, Div Digest Dis, Atlanta, GA 30322 USA.
[Araki, Koichi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
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[Bednarski, Patrick J.] Ernst Moritz Arndt Univ Greifswald, Inst Pharm, Greifswald, Germany.
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[Chiacchiera, Fulvio] IEO, Dept Expt Oncol, Milan, Italy.
[Sachse, Carsten] EMBL, Struct & Computat Biol Unit, Heidelberg, Germany.
[Jungbluth, Heinz] Guys & St Thomas Hosp NHS Fdn Trust, Dept Paediat Neurol, Neuromuscular Serv, Evelinas Children Hosp, London, England.
[Son, Jin H.] Ewha W Univ, Brain & Cognit Sci Pharm, Seoul, South Korea.
[Carneiro, Leticia A. M.] Univ Fed Rio de Janeiro, Inst Microbiol, Dept Immunol, BR-21941 Rio De Janeiro, Brazil.
[Travassos, Leonardo H.] Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, Lab Immunoreceptors & Signaling, Rio De Janeiro, Brazil.
[Pereira, Gustavo J. S.; Smaili, Soraya S.; Ureshino, Rodrigo P.] Univ Fed Sao Paulo, Dept Pharmacol, Paulista Sch Med, Sao Paulo, Brazil.
[Brunetti-Pierri, Nicola] Fed II Univ, Dept Translat Med, Naples, Italy.
[Ballabio, Andrea; Parenti, Giancarlo] Fed II Univ, Telethon Inst Genet & Med TIGEM, Dept Med & Translat Sci, Naples, Italy.
[Yu, Xiao-Fang] Jilin Univ, Hosp 1, Changchun 130023, Jilin, Peoples R China.
[Ge, Pengfei] Jilin Univ, Hosp 1, Dept Neurosurg, Changchun 130023, Jilin, Peoples R China.
[Hernandez, Carlos] Hosp Dr Peset, FISABIO, Valencia, Spain.
[Speck, Peter G.] Flinders Univ S Australia, Sch Biol Sci, Bedford Pk, SA, Australia.
[Jia, Kailiang] Florida Atlantic Univ, Dept Biol Sci, Jupiter, FL USA.
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[Cassinelli, Giuliana; Folini, Marco; Lanzi, Cinzia; Zaffaroni, Nadia] Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol & Mol Med, Milan, Italy.
[Chen, Si; Guo, Lei] NCTR, FDA, Div Biochem Toxicol, Jefferson, AR USA.
[Schwarten, Melanie; Willbold, Dieter] Forschungszentrum Juelich, Struct Biochem ICS 6, Julich, Germany.
[Kumar, Rakesh] George Washington Univ, Dept Biochem & Mol Med, Washington, DC USA.
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[Gutierrez, Maximiliano G.] Francis Crick Inst, Mill Hill Lab, London, England.
[Dumit, Veronica I.] Univ Freiburg, Ctr Biol Syst Anal ZBSA, Core Facil Prote, Hugstetter Str 55, D-79106 Freiburg, Germany.
[Weindl, Guenther] Free Univ Berlin, Inst Pharm Pharmacol & Toxicol, Berlin, Germany.
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[Becker, Christoph] Univ Erlangen Nurnberg, Dept Med 1, D-91054 Erlangen, Germany.
[Lei, Qun-Ying] Fudan Univ, Shanghai Med Coll, Dept Biochem & Mol Biol, Sch Basic Med Sci,Inst Biomed Sci, Shanghai 200433, Peoples R China.
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[Du, Lihuan] Fujian Prov Hosp, Dept Urol, Fuzhou, Peoples R China.
[Skwarska, Anna] Gdansk Univ Technol, Dept Pharmaceut Technol & Biochem, Gdansk, Poland.
[Chang, Ta Yuan] Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH USA.
[Leib, David A.] Geisel Sch Med Dartmouth, Dept Microbiol & Immunol, Lebanon, NH USA.
[Yang, Wannian] Weis Ctr Res, Geisinger Clin, Danville, PA 17822 USA.
[Murthy, Aditya] Genentech Inc, Dept Canc Immunol, San Francisco, CA 94080 USA.
[Campagne, Menno van Lookeren] Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA.
[Bingol, Baris] Genentech Inc, Dept Neurosci, San Francisco, CA 94080 USA.
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[Brown, Eric J.] Genentech Inc, Immunol & Infect Dis, San Francisco, CA 94080 USA.
[Braus, Gerhard H.; Popova, Blagovesta] Univ Gottingen, Dept Mol Microbiol & Genet, Inst Microbiol & Genet, D-37073 Gottingen, Germany.
[Poggeler, Stefanie] Univ Gottingen, Inst Microbiol & Genet, Dept Genet Eukaryot Microorganisms, D-37073 Gottingen, Germany.
[Vasko, Radovan] Univ Gottingen, Dept Nephrol & Rheumatol, D-37073 Gottingen, Germany.
[Krick, Roswitha; Thumm, Michael] Univ Gottingen, Inst Cellular Biochem, D-37073 Gottingen, Germany.
[Liotta, Lance A.] George Mason Univ, Manassas, VA USA.
[Hawley, Robert G.] George Washington Univ, Dept Anat & Regenerat Biol, Washington, DC USA.
[Hawley, Teresa S.] George Washington Univ, Flow Cytometry Core Facil, Washington, DC USA.
[Moussa, Charbel E-H] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20007 USA.
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[Suzuki, Yuichiro J.] Georgetown Univ, Dept Physiol & Pharmacol, Washington, DC USA.
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[Albanese, Chris] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Pathol, Washington, DC USA.
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[Lokeshwar, Bal L.] Georgia Regents Univ, Ctr Canc, Dept Med, Augusta, GA USA.
[Hill, William D.] Georgia Regents Univ, Dept Neurol, Augusta, GA USA.
[Hill, William D.] Georgia Regents Univ, Dept Orthopaed Surg, Augusta, GA USA.
[Hill, William D.] Georgia Regents Univ, Inst Regenerat & Reparat Med, Augusta, GA USA.
[Atherton, Sally S.] Georgia Regents Univ, Med Coll Georgia, Augusta, GA USA.
[Chen, Jian-Kang; Dong, Zheng; Hill, William D.; Xu, Jinxian] Georgia Regents Univ, Med Coll Georgia, Dept Cellular Biol & Anat, Augusta, GA USA.
[Chen, Jian-Kang; Xu, Jinxian] Georgia Regents Univ, Med Coll Georgia, Dept Med, Augusta, GA USA.
[Oehme, Ina] German Canc Res Ctr, Clin Cooperat Unit CCU Pediat Oncol, Heidelberg, Germany.
[Hamacher-Brady, Anne] German Canc Res Ctr, Lysosomal Syst Biol, Heidelberg, Germany.
[Brady, Nathan] German Canc Res Ctr, Syst Biol Cell Death Mech, Heidelberg, Germany.
[Hoeglinger, Guenter U.] German Ctr Neurodegenerat Dis DZNE, Munich, Germany.
[Grune, Tilman] German Inst Human Nutr, Dept Mol Toxicol, Nuthetal, Germany.
[Vandenabeele, Peter] Univ Ghent, Dept Biomed Mol Biol, Inflammat Res Ctr, VIB,Methusalem Program, B-9000 Ghent, Belgium.
[Menendez, Javier A.] ICO, Girona Biomed Res Inst IDIBGI, Catalonia, Spain.
[Auburger, Georg; Gispert, Suzana; Klinkenberg, Michael] Goethe Univ, Sch Med, Expt Neurol, Frankfurt, Germany.
[Doetsch, Volker; Rogov, Vladimir V.] Goethe Univ Frankfurt, Inst Biophys Chem, D-60054 Frankfurt, Germany.
[Dikic, Ivan; Grumati, Paolo] Goethe Univ, Sch Med, Inst Biochem 2, Frankfurt, Germany.
[Dikic, Ivan; Grumati, Paolo] Buchmann Inst Mol Life, Frankfurt, Germany.
[Schaefer, Liliana] Goethe Univ, Inst Pharmacol & Toxicol, Frankfurt, Germany.
[Fulda, Simone] Goethe Univ, Inst Expt Canc Res Pediat, Frankfurt, Germany.
[Hamann, Andrea; Knuppertz, Laura; Osiewacz, Heinz D.] Goethe Univ, Inst Mol Biosci, Mol Dev Biol, Frankfurt, Hesse, Germany.
[Veras, Patricia S. T.] Fundacao Oswaldo Cruz, FIOCRUZ BA, Goncalo Moniz Res Ctr, Lab Pathol & Biointervent, Salvador, BA, Brazil.
[Gwak, Ho-Shin] Grad Sch Canc Sci & Policy, Dept Syst Canc Sci, Goyang, South Korea.
[Choi, Eun-Kyoung] Hallym Univ, Grad Sch, Chunchon, Kangwon Do, South Korea.
[Anoopkumar-Dukie, Shailendra; Grant, Gary Dean] Griffith Univ, Menzies Hlth Inst Queensland, Nathan, Qld 4111, Australia.
[Leng, Shuilong] Guangzhou Med Univ, Dept Human Anat, Sch Basic Sci, Guangzhou, Guangdong, Peoples R China.
[Sakakura, Koichi] Gunma Univ, Grad Sch Med, Dept Otolaryngol Head & Neck Surg, Gunma, Japan.
[Sato, Miyuki] Gunma Univ, Lab Mol Membrane Biol, Inst Mol & Cellular Regulat, Gunma, Japan.
[Sato, Ken] Gunma Univ, Lab Mol Traff, Inst Mol & Cellular Regulat, Gunma, Japan.
[Bravo-San Pedro, Jose M.; Galluzzi, Lorenzo; Izzo, Valentina; Pietrocola, Federico; Sica, Valentina] Gustave Roussy Canc Campus, Villejuif, France.
[Kroemer, Guido] Gustave Roussy Comprehens Canc Ctr, Villejuif, France.
[Chouaib, Salem; Mami-Chouaib, Fathia] Inst Gustave Roussy, Villejuif, France.
[Kim, Deok Ryong] Gyeongsang Natl Univ, Sch Med, Dept Biochem & Convergence Med Sci, JinJu, Gyeongsang, South Korea.
[Kim, Deok Ryong] Inst Hlth Sci, JinJu, South Korea.
[Leibowitz, Gil] Hadassah Hebrew Univ, Med Ctr, Endocrinol & Metab Serv, Dept Med, Jerusalem, Israel.
[Kakhlon, Or] Hadassah Hebrew Univ, Med Ctr, Dept Neurol, Jerusalem, Israel.
[Kang, Tae-Cheon] Hallym Univ, Dept Anat & Neurobiol, Coll Med, Kangwon Do, South Korea.
[Choi, Eun-Kyoung] Hallym Univ, Dept Biomed Gerontol, Chunchon, Kangwon Do, South Korea.
[Kim, Yong-Sun] Hallym Univ, Dept Microbiol, Coll Med, Chunchon, Gangwon, South Korea.
[Ko, Young Ho] Hallym Univ, Ilsong Inst Life Sci, Chunchon, South Korea.
[Suh, Sang Won] Hallym Univ, Sch Med, Dept Physiol, Chunchon, South Korea.
[Azad, Neelam; Iyer, Anand Krishnan V.] Hampton Univ, Dept Pharmaceut Sci, Sch Pharm, Hampton, VA 23668 USA.
[Yang, Yi] Hangzhou Normal Univ, Dept Pharmacol, Sch Med, Hangzhou, Zhejiang, Peoples R China.
[Behrens, Georg M. N.] Hannover Med Sch, Dept Clin Immunol & Rheumotol, Hannover, Germany.
[Gaestel, Matthias; Menon, Manoj B.] Hannover Med Sch, Dept Biochem, Hannover, Germany.
[Thum, Thomas] Hannover Med Sch, Inst Mol & Translat Therapeut Strategies IMTTS, Hannover, Germany.
[Bae, Ok-Nam] Hanyang Univ, Coll Pharm, Ansan, South Korea.
[Wang, Dong] Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin, Heilongjiang, Peoples R China.
[Xu, Hongwei] Harbin Med Univ, Dept Immunol, Heilongjiang Prov Key Lab Infect & Immun, Harbin, Peoples R China.
[Chou, Tsui-Fen] Harbor UCLA Med Ctr, Torrance, CA 90509 USA.
[Chou, Tsui-Fen] Los Angeles Biomed Res Inst, Div Med Genet, Dept Pediat, Torrance, CA USA.
[Geng, Jiefei; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Xavier, Ramnik J.] Broad Inst, Boston, MA USA.
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[Kimmelman, Alec C.; Mancias, Joseph D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Mancias, Joseph D.] Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA.
[Harper, J. Wade; Yuan, Junying] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Irazoqui, Javier E.] Harvard Univ, Sch Med, Lab Comparat Immunol,Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis,Res Inst, Boston, MA 02115 USA.
[Narendra, Derek P.] Harvard Univ, Sch Med, Neurol Residency Program, Brigham & Womens Hosp, Boston, MA 02115 USA.
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[Notomi, Shoji; Vavvas, Demetrios G.] Harvard Univ, Sch Med, Ophthalmol, Boston, MA 02115 USA.
[Airoldi, Edoardo M.] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA.
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[Rasse, Tobias M.] Heidelberg Univ, Deutsch Krebsforschungszentrum, Proteostasis Neurodegenerat Dis B180, CHS Res Grp CellNetworks, Heidelberg, Germany.
[Schuck, Sebastian] Heidelberg Univ, Zentrum Mol Biol Univ Heidelberg ZMBH, Heidelberg, Germany.
[Ventura, Natascia] Univ Dusseldorf, Inst Clin Chem, Dusseldorf, Germany.
[Ventura, Natascia] Diagnost Lab, Fac Med, Dusseldorf, Germany.
[Willbold, Dieter] Univ Dusseldorf, Inst Phys Biol, Dusseldorf, Germany.
[Stork, Bjoern] Univ Dusseldorf, Inst Mol Med, Dusseldorf, Germany.
[Schmitz, Ingo] Helmholtz Ctr Infect Res, Syst Oriented Immunol & Inflammat Res, Braunschweig, Germany.
[Korhonen, Laura] Univ Helsinki, Cent Hosp, Fac Med, Div Child Psychiat, Helsinki, Finland.
[Screen, Mark] Univ Helsinki, Dept Med Genet, Helsinki, Finland.
[Zhou, Guang-Zhou] Henan Univ Technol, Coll Bioengn, Zhengzhou 450000, Henan Province, Peoples R China.
[Tanji, Kunikazu] Hirosaki Univ, Grad Sch Med, Hirosaki, Aomori, Japan.
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[Kihara, Akio] Hokkaido Univ, Fac Pharmaceut Sci, Kita 12, Sapporo, Hokkaido 060, Japan.
[Ubukata, Makoto] Hokkaido Univ, Res Fac Agr, Sapporo, Hokkaido, Japan.
[Li, Min; Song, Ju-Xian] Hong Kong Baptist Univ, Sch Chinese Med, Kowloon, Hong Kong, Peoples R China.
[Law, Helen Ka-wai; Siu, Parco M.] Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Fac Hlth & Social Sci, Kowloon, Hong Kong, Peoples R China.
[Ip, Nancy Y.] Hong Kong Univ Sci & Technol, Kowloon, Hong Kong, Peoples R China.
[Rautou, Pierre-Emmanuel] Hop Beaujon, Paris, France.
[Kroemer, Guido] Hop Europeen Georges Pompidou, AP HP, Paris, France.
[Cerella, Claudia; Radogna, Flavia] Hop Kirchberg, Lab Biol Mol & Cellulaire Canc, Luxembourg, Luxembourg.
[Lemoine, Antoinette] Hop Univ Paris Sud Biochim & Oncogenet, Hop Paul Brousse, Villejuif, France.
[Brumell, John H.] Hosp Sick Children, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
[Mena, Maria A.] Hosp Univ Ramon Cajal, CIBERNED, Dept Neurobiol, Madrid, Spain.
[Frigo, Daniel E.] Houston Methodist Res Inst, Genom Med Program, Houston, TX USA.
[Kang, Chanhee] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Levine, Beth] Howard Hughes Med Inst, Dallas, TX USA.
[Yan, Xianghua] Huazhong Agr Univ, Coll Anim Sci & Technol, Wuhan, Hubei, Peoples R China.
[Jiang, Yongjun; Liu, Xueqin] Huazhong Agr Univ, Dept Aquat Anim Med, Coll Fisheries, Wuhan, Peoples R China.
[Liu, Zexian; Xue, Yu] Huazhong Univ Sci & Technol, Dept Biomed Engn, Coll Life Sci & Technol, Wuhan 430074, Hubei, Peoples R China.
[Kaparakis-Liaskos, Maria] Ctr Innate Immun & Infect Dis, Hudson Inst Med Res, Melbourne, Vic, Australia.
[Shen, Chiung-Chyi] Hungkuang Univ, Dept Phys Therapy, Taichung, Taiwan.
[Aranda, Agustin] Inst Agrochem & Food Technol, IATA CSIC, Paterna, Valencia, Spain.
[Menezes, Regina; dos Santos, Claudia Nunes] Inst Biol Expt & Tecnol, iBET, Oeiras, Portugal.
[Huang, Yong] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA.
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[Yue, Zhenyu] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA.
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[Le Cam, Laurent] Inst Rech Cancerol Montpellier, ICM, Montpellier, France.
[Pujol, Aurora] ICREA Catalan Inst Res & Adv Studies, Catalonia, Spain.
[Vaccari, Thomas] FIRC Inst Mol Oncol, IFOM, Milan, Italy.
[Sonawane, Avinash] IIT Univ, Sch Biotechnol, Bhubaneswar, Orissa, India.
[Barreiro, Esther] Pompeu Fabra Univ, Barcelona Biomed Res Pk, Dept Resp Med, Lung Canc & Muscle Res Grp,IMIM Hosp Mar CIBERES, Barcelona, Spain.
[Thurston, Teresa L. M.] Univ London Imperial Coll Sci Technol & Med, MRC Ctr Mol Bacteriol & Infect, London, England.
[Braga, Vania M. M.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England.
[de Belleroche, Jackie] Univ London Imperial Coll Sci Technol & Med, Neurogenet Grp, Div Brain Sci, London, England.
[Mostowy, Serge] Univ London Imperial Coll Sci Technol & Med, Microbiol Sect, MRC Ctr Mol Bacteriol & Infect, London, England.
[Lee, Michael] Incheon Natl Univ, Div Life Siences, Inchon, South Korea.
[Balaji, Kithiganahalli Narayanaswamy] Indian Inst Sci, Dept Microbiol & Cell Biol, Bangalore 560012, Karnataka, India.
[Somasundaram, Kumaravel] Indian Inst Sci Microbiol & Cell Biol, Bangalore, Karnataka, India.
[Dubey, Vikash Kumar] Indian Inst Technol, Dept Biosci & Bioengn, Gauhati, Assam, India.
[Maiti, Tapas K.] Indian Inst Technol, Dept Biotechnol, Kharagpur 721302, W Bengal, India.
[Justice, Matthew J.] Indiana Univ Sch Med, Biochem & Mol Biol, Denver, CO USA.
[Dong, X. Charlie; Roach, Peter J.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA.
[Naidu, Samisubbu R.] Indiana Univ Sch Med, Dept Dermatol, Indianapolis, IN 46202 USA.
[Broxmeyer, Hal E.] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA.
[Boulton, Michael E.] Indiana Univ Sch Med, Dept Ophthalmol, Indianapolis, IN 46202 USA.
[Khambu, Bilon; Yin, Xiao-Ming] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA.
[Lahm, Tim] Indiana Univ Sch Med, Richard L Roudebush VA Med Ctr, Div Pulm, Crit Care Sleep & Occupat Med, Indianapolis, IN 46202 USA.
[Hong, Yonggeun] Inje Univ, Dept Rehabil Sci, Coll Biomed Sci & Engn, u HARC, Gimhae, South Korea.
[Corazzari, Marco] INMI IRCCS L Spallanzani, Rome, Italy.
[Bruhat, Alain] Ctr Clermont Theix, INRA, Nutr Humaine UMR 1019, St Genes Champanelle, France.
[Favier, Francois B.] INRA, Dynam Musculaire & Metab UMR866, F-34060 Montpellier, France.
[Seiliez, Iban] INRA, UR1067, Nutr Metab Aquaculture, St Pee Sur Nivelle, France.
[Luciano, Federic] INSERM, U1065, C3M, Team 2, Nice, France.
[Belaid, Amine; Brest, Patrick; Mograbi, Baharia] IRCAN, INSERM, U1081, CNRS UMR7284, Nice, France.
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[Giuliano, Sandy; Pages, Gilles] Univ Nice Sophia Antipolis, Inst Res Canc & Ageing Nice, CNRS UMR 7284, INSERM U1081, F-06189 Nice, France.
[Dupuis, Luc] INSERM, U1118, Mecanismes Cent & Periphet Neurodegenerescence, Strasbourg, France.
[Kepp, Oliver; Torriglia, Alicia] INSERM, U1138, Paris, France.
[Pallet, Nicolas] INSERM, U1147, Paris, France.
[Mechta-Grigoriou, Fatima] Inst Curie, INSERM U830, Stress & Canc Lab, Paris, France.
[Benard, Giovanni] INSERM U862, Neuroctr Magendie, Bordeaux, France.
[Le Cam, Laurent] INSERM U896, Montpellier, France.
[Duran, Raul V.; Villar, Victor H.] Univ Bordeaux, INSERM U916, Inst Europeen Chim & Biol, Pessac, France.
[Teixeira-Clerc, Fatima] INSERM U955, Fac Med Creteil, UMR S955, Creteil, France.
[Laporte, Jocelyn; Nicot, Anne-Sophie] Univ Strasbourg, INSERM U964, CNRS UMR7104, Dept Translat Med,IGBMC, Illkirch Graffenstaden, France.
[Andrieu-Abadie, Nathalie] Ctr Rech Cancerol Toulouse, INSERM UMR1037, Toulouse, France.
[Dugail, Isabelle] INSERM UMRS 1166, Unite Rech Malad Cardiovasc Metab & Nutr, Paris, France.
[Kroemer, Guido] INSERM, Cordeliers Res Canc, Paris, France.
[Bulavin, Dmitry V.] INSERM, UMR CNRS 7284 U1081, Nice, France.
[Gatti, Evelina; Pierre, Philippe] INSERM, U1104, Marseille, France.
[Corti, Olga] INSERM, U1127, CNRS, UMR 7225, Paris, France.
[Bravo-San Pedro, Jose M.; Galluzzi, Lorenzo; Izzo, Valentina; Pietrocola, Federico; Sica, Valentina] INSERM, U1138, Paris, France.
[Rautou, Pierre-Emmanuel] INSERM, U970, Paris, France.
[Roue, Gael] IDIBAPS, Hemato Oncol Dept, Barcelona, Spain.
[Francois, Aurelie] Inst Cancerol Lorraine, Vandoeuvre Les Nancy, France.
[Le Cam, Laurent] Inst Canc Montpellier, Montpellier, France.
[Fiorito, Filomena] Ist Zooprofilattico Sperimentale Mezzogio, Dept Chem, Naples, Italy.
[Echard, Arnaud] Inst Pasteur, CNRS URA2582, Cell Biol & Infect Dept, Membrane Traff & Cell Div Lab, Paris, France.
[Lafont, Frank] Univ Lille, Ctr Infect & Immun Lille, Inst Pasteur Lille, CNRS,INSERM,Lille Reg Univ Hosp Ctr, Lille, France.
[Colucci-Guyon, Emma] Inst Pasteur, CNRS, URA2578, Unite Macrophages & Dev Immunite,Dept Biol Dev &, Paris, France.
[Albert, Matthew L.] Inst Pasteur, Dept Immunol, Paris, France.
[Lecuit, Marc] Inst Pasteur, INSERM, Biol Infect Unit, Paris, France.
[Papackova, Zuzana] Inst Clin & Expt Med, Ctr Med Expt, Dept Metab & Diabet, Prague, Czech Republic.
[Bianchi, Michele Wolfe] Univ Paris Saclay, Inst Integrat Biol Cell, Gif Sur Yvette, France.
[Zorzano, Antonio] Barcelona Inst Sci & Technol, Inst Res Biomed IRB Barcelona, Barcelona, Spain.
[Triola, Gemma] Spanish Res Council IQAC CSIC, Inst Adv Chem Catalonia, Dept Biomed Chem, Barcelona, Spain.
[Ryabovol, Victoria] Inst Biochem & Biophys, Kazan, Russia.
[Almonte-Beceril, Maylin] Inst Biomed Invest INIBIC, Inflamat & Regenerat Med, Coruna, Spain.
[Jones, Chris] Inst Canc Res, Div Mol Pathol & Canc Therapeut, London SW3 6JB, England.
[Zhivotovsky, Boris] Karolinska Inst, Inst Environm Med, Div Toxicol, Stockholm, Sweden.
[Chauhan, Santosh] Inst Life Sci, Bhubaneswar, Odisa, India.
[Ishaq, Mohammad] Inst Microbial Technol IMTECH, Cell Biol & Immunol Div, Chandigarh, India.
[Vachova, Libuse] Inst Microbiol ASCR, Vvi, Prague, Czech Republic.
[Penninger, Josef M.] Austrian Acad Sci, IMBA, Inst Mol Biotechnol, A-1010 Vienna, Austria.
[Scovassi, A. Ivana] CNR, Inst Mol Genet, Pavia, Italy.
[Stulik, Jiri] FMHS UO, Inst Mol Pathol & Biol, Hradec Kralove, Czech Republic.
[Stepkowski, Tomasz M.] Ctr Radiobiol & Biol Dosimetry, Inst Nucl Chem & Technol, Dorodna, Poland.
[Vescovi, Eleonora Garcia] Inst Biol Mol & Celular Rosario IBR CONICET, Rosario, Argentina.
[Lazo, Pedro A.] Hosp Univ Salamanca, Inst Invest Biomed Salamanca IBSAL, Salamanca, Spain.
[Martin-Sanz, Paloma] Ctr Invest Biomed Red Enfermedade Hepat & Digest, Inst Invest Biomed Albert Sols, CSIC UAM, Madrid, Spain.
[Valverde, Angela M.] CSIC UAM, Inst Invest Biomed Albert Sols, Madrid, Spain.
[Fernandez-Checa, Jose C.] CSIC IDI BAPS, Inst Invest Biomed Barcelona, Barcelona, Spain.
[Fernandez-Checa, Jose C.] CIBEREHD, ISCIII, Ctr Invest Red Enfermedades Hepat & Digest, Barcelona, Spain.
[Oliver, F. Javier] CSIC, IPBLN, Granada, Spain.
[Menezes, Regina; dos Santos, Claudia Nunes] Univ Nova Lisboa, Inst Tecnol Quim & Biol Antonio Xavier, P-2780156 Oeiras, Portugal.
[Moita, Luis Ferreira] Inst Gulbenkian Ciencias, Oeiras, Portugal.
[Garcia-Ruiz, Carmen] Hosp Clin Barcelona IDIBAPS, Inst Invest Biomed Barcelona IIBB CSIC, Liver Unit, Barcelona, Spain.
[Garcia-Ruiz, Carmen] CIBEREHD, Barcelona, Spain.
[Wappner, Pablo] Inst Leloir, Buenos Aires, DF, Argentina.
[Alonso, Covadonga; Galindo, Inmaculada; Munoz-Moreno, Raquel] Inst Nacl Invest & Tecnol Agr & Alimentaria INIA, Dept Biotecnol, Madrid, Spain.
[Perez-de la Cruz, Veronica] Inst Nacl Neurol & Neurocirug, Neurochem Unit, Mexico City, DF, Mexico.
[Pineda, Benjamin] Inst Nacl Neurol & Neurocirug, Neuroimmunol & Neuro Oncol Unit, Mexico City, DF, Mexico.
[Menna-Barreto, Rubem F. S.] Fiocruz MS, Inst Oswaldo Cruz, Lab Biol Celular, BR-21045900 Rio De Janeiro, Brazil.
[Chandra, Pallavi; Kumar, Dhiraj] Int Ctr Genet Engn & Biotechnol, Immunol Grp, New Delhi, India.
[Kanthasamy, Anumantha G.] Iowa State Univ, Dept Biomed Sci, Iowa Ctr Adv Neurotoxicl, Ames, IA USA.
[Bassham, Diane C.] Iowa State Univ, Dept Genet Dev & Cell Biol, Ames, IA USA.
[MacIntosh, Gustavo C.] Iowa State Univ, Roy J Carver Dept Biochem Biophys & Mol Biol, Ames, IA USA.
[Fusco, Carmela; Merla, Giuseppe; Micale, Lucia] IRCCS Casa Sollievo Sofferenza, Med Genet Unit, San Giovanni Rotondo, FG, Italy.
[Fornai, Francesco; Sciarretta, Sebastiano] IRCCS Neuromed, Pozzilli, IS, Italy.
[Ferraro, Elisabetta] IRCCS San Raffaele Pisana, Lab Skeletal Muscle Dev & Metab, Rome, Italy.
[Cecconi, Francesco; D'Amelio, Marcello; Molinari, Marco; Viscomi, Maria Teresa] IRCCS Santa Lucia Fdn, Rome, Italy.
[Campello, Silvia] IRCCS Santa Lucia Fdn, Dept Expt Neurosci, Rome, Italy.
[Crippa, Valeria] IRCCS C Mondino Natl Neurol Inst, Expt Neurobiol Lab, Pavia, Italy.
[Facchiano, Antonio] IRCCS, Ist Dermopatico Immacolata, Rome, Italy.
[Cantoni, Lavinia] IRCCS Ist Ric Farmacol Mario Negri, Dept Mol Biochem & Pharmacol, Milan, Italy.
[Albani, Diego] IRCCS Ist Ric Farmacol Mario Negri, Dept Neurosci, Milan, Italy.
[Matarese, Giuseppe] IRCCS MultiMed, Milan, Italy.
[Marin, Concepcio] Inst Invest Biomed August Pi & Sunyer IDIBAPS, IRCE, Barcelona, Spain.
[Gongora, Celine] INSERM, IRCM, Inst Rech Cancerol Montpellier, U896, Montpellier, France.
[Pattingre, Sophie] IRCM, Inst Rech Cancerol Montpellier, Montpellier, France.
[Cottet, Sandra; Schorderet, Daniel F.] IRO, Inst Res Ophthalmol, Sion, Switzerland.
[Chiariello, Mario; Colecchia, David] Ist Fisiol Clin, Siena, Italy.
[Bachetti, Tiziana; Ceccherini, Isabella] UOC Med Genet, Ist Giannina Gaslini, Genoa, Italy.
[Grimaldi, Benedetto] Ist Italiano Tecnol, Dept Drug Discovery & Dev, Lab Mol Med, Genoa, Italy.
[Giovannetti, Elisa] Univ Pisa, AIRC Start UP Unit, Canc Pharmacol Lab, Pisa, Italy.
[Merlini, Luciano] Ist Ortopedico Rizzoli IOR IRCCS, Lab Musculoskeletal Cell Biol, Bologna, Italy.
[Ortona, Elena; Pierdominici, Marina] Ist Super Sanita, Dept Cell Biol & Neurosci, Viale Regina Elena 299, I-00161 Rome, Italy.
[Salvioli, Rosa] Ist Super Sanita, Dept Haematol Oncol & Mol Med, Viale Regina Elena 299, I-00161 Rome, Italy.
[Coccia, Eliana M.] Ist Super Sanita, Dept Infect Parasit & Immunomediated Dis, Viale Regina Elena 299, I-00161 Rome, Italy.
[Matarrese, Paola] Ist Super Sanita, Dept Therapeut Res & Med, Evaluat Sect Cell Aging Degenerat & Gender Med, Viale Regina Elena 299, I-00161 Rome, Italy.
[Giammarioli, Anna Maria; Malorni, Walter] Ist Super Sanita, Viale Regina Elena 299, I-00161 Rome, Italy.
[Chiariello, Mario; Colecchia, David] Ist Toscano Tumori, Siena, Italy.
[Condello, Maria; Meschini, Stefania] Italian Natl Inst Hlth, Dept Technol & Hlth, Rome, Italy.
[Schiavi, Alfonso; Ventura, Natascia] IUF Leibniz Res Inst Environm Med, Dusseldorf, Germany.
[Stoka, Veronika; Turk, Boris; Turk, Vito] Jozef Stefan Inst, Dept Biochem & Mol & Struct Biol, Ljubljana, Slovenia.
[Karmakar, Parimal] Jadavpur Univ, Life Sci & Biotechnol, Kolkata, W Bengal, India.
[Gandy, Sam] James J Peters VA Med Ctr, Bronx, NY USA.
[Saran, Shweta] Jawaharlal Nehru Univ, Sch Life Sci, New Delhi 110067, India.
[Platanias, Leonidas C.] Jesse Brown VA Med Ctr, Dept Med, Chicago, IL USA.
[Song, Wei] McGill Univ, Jewish Gen Hosp, Bloomfield Ctr Res Aging, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada.
[Schipper, Hyman M.] McGill Univ, Jewish Gen Hosp, Dept Neurol & Neurosurg, Dept Med, Montreal, PQ H3T 1E2, Canada.
[Topisirovic, Ivan] McGill Univ, Jewish Gen Hosp, Dept Oncol, Montreal, PQ H3T 1E2, Canada.
[Yu, Huixin; Zhang, Li] Jiangsu Inst Nucl Med, Wuxi, Jiangsu, Peoples R China.
[Su, Zhaoliang] Jiangsu Univ, Dept Immunol, Zhenjiang, Jiangsu, Peoples R China.
[Guo, Wenjie] Jiangsu Univ, Sch Pharm, Zhenjiang, Jiangsu, Peoples R China.
[Araya, Jun] Jikei Univ, Sch Med, Div Resp Dis, Dept Internal Med, Tokyo, Japan.
[Shimada, Yohta] Jikei Univ, Sch Med, Res Ctr Med Sci, Div Gene Therapy, Tokyo, Japan.
[Xu, Ye] Jilin Med Univ, Med Res Lab, Jilin, Jilin Province, Peoples R China.
[He, Rong-Rong] Jinan Univ, Anti Stress & Hlth Ctr, Coll Pharm, Guangzhou, Guangdong, Peoples R China.
[He, Xian-Hui; Ouyang, Dong-yun] Jinan Univ, Dept Immunobiol, Coll Life Sci & Technol, Guangzhou, Guangdong, Peoples R China.
[Yang, Xuesong] Jinan Univ, Coll Med, Div Histol & Embryol, Guangzhou, Guangdong, Peoples R China.
[Yan, Bo] Jining Med Univ, Shandong Prov Sino US Cooperat Res Ctr Translat M, Jining, Shandong, Peoples R China.
[Chen, Gang] Fudan Univ, Jinshan Hosp, Dept Urol, Shanghai 200433, Peoples R China.
[Prange, Reinhild] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Med Microbiol & Hyg, D-55122 Mainz, Germany.
[Kesari, Santosh] John Wayne Canc Inst, Dept Neurosci, Santa Monica, CA USA.
[Coppens, Isabelle] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Malaria Res Inst, Dept Mol Microbiol & Immunol, Baltimore, MD 21287 USA.
[Ratovitski, Edward A.; Sesaki, Hiromi] Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA.
[Wong, G. William] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA.
[Wong, G. William] Ctr Metab & Obes Res, Baltimore, MD USA.
[Dawson, Ted M.] Johns Hopkins Univ Hosp, Sch Med, Dept Neurol Neurosci & Pharmacol, Neuroregenerat Program,Inst Cell Engn, Baltimore, MD 21287 USA.
[Dawson, Ted M.] Johns Hopkins Univ, Sch Med, Dept Mol Sci, Neuroregenerat Program,Inst Cell Engn, Baltimore, MD 21287 USA.
[Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21287 USA.
[Semenza, Gregg L.] McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Dawson, Valina L.] Johns Hopkins Univ Hosp, Sch Med, Neuroregenerat & Stem Cell Programs, Inst Cell Engn,Dept Neurol,Dept Physiol, Baltimore, MD 21287 USA.
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[Bosch, Jurgen] Johns Hopkins, Bloomberg Sch Publ Hlth, Dept Biochem & Mol Biol, Baltimore, MD USA.
[Bosch, Jurgen] Johns Hopkins Malaria Res Inst, Baltimore, MD USA.
[Handa, James T.] Johns Hopkins, Sch Med, Wilmer Eye Inst, Baltimore, MD USA.
[Imai, Yuzuru] Juntendo Univ, Dept Res Parkinsons Dis, Tokyo, Japan.
[Koike, Masato] Juntendo Univ, Grad Sch Med, Dept Cell Biol & Neurosci, Tokyo, Japan.
[Fujitani, Yoshio; Watada, Hirotaka] Juntendo Univ, Grad Sch Med, Dept Endocrinol & Metab, Tokyo, Japan.
[Nukina, Nobuyuki] Juntendo Univ, Grad Sch Med, Dept Neurosci Neurodegenerat Disorders, Tokyo, Japan.
[Ueno, Takashi] Juntendo Univ, Grad Sch Med, Lab Prote & Biomol Sci, Tokyo, Japan.
[Tanida, Isei; Uchiyama, Yasuo] Juntendo Univ, Sch Med, Dept Cell Biol & Neurosci, Tokyo 113, Japan.
[Yamashina, Shunhei] Juntendo Univ, Sch Med, Dept Gastroenterol, Tokyo 113, Japan.
[Kominami, Eiki] Juntendo Univ, Tokyo, Japan.
[Hasui, Kazuhisa] Kagoshima Univ, Grad Sch Med & Dent Sci, Div Human Pathol, Dept Oncol,Course Adv Therapeut, Kagoshima 890, Japan.
[Setoguchi, Takao] Kagoshima Univ, Near Future Locomoter Organ Med Creat Course, Grad Sch Med & Dent Sci, Kagoshima 890, Japan.
[Lee, Gyun Min] Korea Adv Inst Sci & Technol, Dept Biol Sci, Daejon, South Korea.
[Okazaki, Toshiro] Kanazawa Med Univ, Dept Med, Kanazawa, Ishikawa, Japan.
[Koya, Daisuke] Kanazawa Med Univ, Diabetol & Endocrinol, Kanazawa, Ishikawa, Japan.
[Sasaki, Motoko] Kanazawa Univ, Grad Sch Med Sci, Dept Human Pathol, Kanazawa, Ishikawa, Japan.
[Wong, Richard W.] Kanagawa Univ, Cell Bion Unit, Dept Biol, Fac Nat Syst,Inst Sci & Engn, Kanagawa, Ishikawa, Japan.
[Wong, Richard W.] Kanagawa Univ, Lab Mol & Cellular Biol, Dept Biol, Fac Nat Syst,Inst Sci & Engn, Kanagawa, Ishikawa, Japan.
[Lee, Stella Y.; Roelofs, Jeroen] Kansas State Univ, Div Biol, Manhattan, KS 66506 USA.
[Chai, Chee-Yin] Kaohsiung Med Univ Hosp, Dept Pathol, Kaohsiung, Taiwan.
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[Khan, Muzamil Majid] Karlsruhe Inst Technol, Inst Toxicol & Genet, D-76021 Karlsruhe, Germany.
[Brodin, Bertha; De Milito, Angelo; Joseph, Bertrand; Panaretakis, Theocharis] Karolinska Inst, Canc Ctr Karolinska, Dept Oncol Pathol, Stockholm, Sweden.
[Nilsson, Per] Karolinska Inst, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, Div Neurogeriatr, Huddinge, Sweden.
[McInerney, Gerald M.] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.
[Chagin, Andrei S.; Nader, Gustavo A.; Norberg, Erik] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
[Kaminskyy, Vitaliy O.] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[Takigawa, Nagio] Kawasaki Med Univ, Dept Gen Internal Med 4, Okayama, Japan.
[Hino, Keisuke] Kawasaki Med Univ, Dept Hepatol & Pancreatol, Kurashiki, Okayama, Japan.
[Kwon, Taeg Kyu] Keimyung Univ, Daegu, South Korea.
[Jang, Byoung Kuk] Keimyung Univ, Sch Med, Div Gastroenterol & Hepatol, Dept Internal Med, Daegu, South Korea.
[Ishii, Isao] Keio Univ, Grad Sch Pharmaceut Sci, Dept Biochem, Tokyo, Japan.
[Suzuki, Hidekazu] Keio Univ, Sch Med, Med Educ Ctr, Tokyo, Japan.
[Alloza, Iraide] Basque Fdn Sci, KERBASQUE, Bilbao, Spain.
[Harrath, Abdel Halim] King Saud Univ, Coll Sci, Dept Zool, Riyadh 11451, Saudi Arabia.
[Otsu, Kinya] Kings Coll London, Cardiovasc Div, London WC2R 2LS, England.
[Fanto, Manolis; Jungbluth, Heinz] Kings Coll London, Dept Basic & Clin Neurosci, IoPPN, London WC2R 2LS, England.
[Jungbluth, Heinz] Kings Coll London, Randall Div Cell & Mol Biophys, Muscle Signalling Sect, London, England.
[Shintani, Michiko] Kobe Univ, Grad Sch Hlth Sci, Pathol Lab, Div Med Biophys, Kobe, Hyogo, Japan.
[Matsushita, Takehiko] Kobe Univ, Grad Sch Med, Dept Orthopaed Surg, Kobe, Hyogo, Japan.
[Voitsekhovskaja, Olga V.] Komarov Bot Inst RAS, Plant Ecol Physiol Lab, St Petersburg, Russia.
[Cho, Ssang-Goo] Konkuk Univ, Dept Anim Biotechnol, Seoul, South Korea.
[Lim, Hyunjung Jade] Konkuk Univ, Dept Vet Med, Seoul, South Korea.
[Chung, Hyewon] Konkuk Univ, Sch Med, Dept Ophthalmol, Seoul, South Korea.
[Lee, He-Jin] Konkuk Univ, Sch Med, Dept Anat, Seoul, South Korea.
[Kim, Cheol Hyeon] Korea Canc Ctr Hosp, Dept Internal Med, Seoul, South Korea.
[Lee, Sung-Joon] Korea Univ, Dept Biotechnol, PLUS Grad Sch Life Sci & Biotechnol BK21, Seoul, South Korea.
[Chi, Sung-Gil; Choi, Eui-Ju; Lee, Jae Keun; Wright, Karen L.] Korea Univ, Dept Life Sci & Biotechnol, Seoul, South Korea.
[Chun, Taehoon] Korea Univ, Dept Biotechnol, Coll Life Sci & Biotechnol, Seoul, South Korea.
[Park, Ohkmae K.; Song, Hyun Kyu] Korea Univ, Div Life Sci, Seoul, South Korea.
[Van Den Bosch, Ludo] Katholieke Univ Leuven, Leuven, Belgium.
[Van Den Bosch, Ludo] VIB, Vesalius Res Ctr, Neurobiol Lab, Leuven, Belgium.
[Gunst, Jan; Van den Berghe, Greet; Vanhorebeek, Ilse] Katholieke Univ Leuven, Clin Div, Leuven, Belgium.
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[Decuypere, Jean-Paul] Katholieke Univ Leuven, Dept Abdominal Transplant Surg, Leuven, Belgium.
[Martin, Shaun] Katholieke Univ Leuven, Dept Cellular & Mol Med, Leuven, Belgium.
[Soenen, Stefaan J.] Katholieke Univ Leuven, Dept Imaging & Pathol, Leuven, Belgium.
[Agostinis, Patrizia; Maes, Hannelore] Katholieke Univ Leuven, Lab Cell Death Res & Therapy, Dept Cellular & Mol Med, Campus Gasthuisberg, Leuven, Belgium.
[Bultynck, Geert; Parys, Jan B.] Katholieke Univ Leuven, Lab Mol & Cellular Signaling, Dept Cellular & Mol Med, Leuven, Belgium.
[Ohmuraya, Masaki] Kumamoto Univ, Inst Resource Dev & Anal, Kumamoto, Japan.
[Agam, Galila] Kunming Univ Sci & Technol, Sch Med, Kunmimg, Yunnan, Peoples R China.
[Tanaka, Masaki; Watanabe, Yoshihisa] Kyoto Prefectural Univ Med, Dept Basic Geriatr, Kyoto, Japan.
[Matoba, Satoaki] Kyoto Prefectural Univ Med, Dept Cardiovasc Med, Grad Sch Med Sci, Kyoto, Japan.
[Nagata, Kazuhiro] Kyoto Sangyo Univ, Dept Life Sci, Kyoto 603, Japan.
[Ushioda, Ryo] Kyoto Sangyo Univ, Dept Mol Biosci, Fac Life Sci, Kyoto 603, Japan.
[Goto-Yamada, Shino] Kyoto Univ, Dept Bot, Kyoto, Japan.
[Shioi, Tetsuo] Kyoto Univ, Dept Cardiovasc Med, Kyoto, Japan.
[Asanuma, Katsuhiko] Kyoto Univ, Grad Sch Med, Med Innocat Ctr TMK Project, Kyoto, Japan.
[Cho, Dong-Hyung] Kyung Hee Univ, Grad Sch East Wast Med Sci, Seoul, South Korea.
[Bae, Jae-Sung] Kyungpook Natl Univ, Dept Physiol, Sch Med, Daegu, South Korea.
[Shirabe, Ken] Kyushu Univ, Dept Surg & Sci, Fukuoka 812, Japan.
[Fairlie, W. Douglas; Lee, Erinna F.] Olivia Newton John Canc Res Inst, Melbourne, Vic, Australia.
[Soo, Kai Y.] La Trobe Univ, Dept Biochem & Genet, La Trobe Inst Mol Sci, Melbourne, Vic, Australia.
[Fairlie, W. Douglas; Lee, Erinna F.] La Trobe Univ, Dept Chem & Phys, Melbourne, Vic, Australia.
[Fairlie, W. Douglas; Lee, Erinna F.] La Trobe Univ, Sch Canc Med, Melbourne, Vic, Australia.
[Paganetti, Paolo] Neurodegenerat Grp, Lab Biomed Neurosci NSI EOC, Torricella Taverne, Switzerland.
[Nilsson, Per] RIKEN, Brain Sci Inst, Lab Proteolyt Neurosci, Wako, Saitama, Japan.
[Choi, Eun-Kyoung] Ilsong Inst Life Sci, Lab Cellular Aging & Neurodegenerat, Anyang, Gyeonggi Do, South Korea.
[Mayer, Andreas] Univ Lancaster, Fac Hlth & Med, Div Biomed & Life Sci, Lancaster, England.
[Erenpreisa, Jekaterina] Latvian Biomed Res & Study Ctr, Riga, Latvia.
[Spaink, Herman P.] Leiden Univ, Inst Biol, Leiden, Netherlands.
[Stern, Stephan T.] Leidos Biomedical Res Inc, Frederick Natl Lab Canc Res, Nanotechnol Characterizat Lab, Canc Res Technol Program, Frederick, MD USA.
[Los, Marek] Med Univ Silesia, ENT Dept, Sch Med, Katowice, Poland.
[Kagedal, Katarina; Mohseni, Simin; Ollinger, Karin] Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
[Kurz, Tino] Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.
[Boman, Andrea] Linkoping Univ, Expt Pathol, Dept Clin & Expt Med, Fac Hlth Sci, Linkoping, Sweden.
[Taylor, Mark J.] Univ Liverpool, Liverpool Sch Trop Med, Dept Parasitol, Liverpool L3 5QA, Merseyside, England.
[Shajahan-Haq, Ayesha N.] Georgetown Univ, Med Ctr, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Zhivotovsky, Boris] Lomonosov Moscow State Univ, Fac Basic Med, Moscow, Russia.
[Tooze, Sharon A.] Canc Res UK, London Res Inst, London, England.
[Swanton, Charles] UCL, Inst Canc, London, England.
[Rihn, Bertrand H.] Lorraine Univ, CITHeFOR EA3452, Fac Pharm, Nancy, France.
[Adler, Sharon G.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA.
[Huang, Shile] Louisiana State Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Shreveport, LA 71105 USA.
[Wu, Chunlai] Louisiana State Univ, Hlth Sci Ctr, Neurosci Ctr Excellence, New Orleans, LA 71105 USA.
[Lin, Yong] Lovelace Resp Res Inst, Mol Biol & Lung Canc Program, Albuquerque, NM USA.
[von Schwarzenberg, Karin] Univ Munich, Dept Pharm, Munich, Germany.
[Swaerd, Karl] Lund Univ, Biomed Ctr, Dept Expt Med Sci, Lund, Sweden.
[Berchem, Guy] Luxembourg Inst Hlth, Luxembourg, Luxembourg.
[Berchem, Guy] Ctr Hosp Luxembourg, Luxembourg, Luxembourg.
[Janji, Bassam] Luxembourg Inst Hlth, Lab Expt Hemato Oncol, Dept Oncol, Luxembourg, Luxembourg.
[El-Khoury, Victoria] Luxembourg Inst Hlth, Dept Oncol, Luxembourg, Luxembourg.
[Jutten, Barry; Rouschop, Kasper M.] Maastricht Univ, Maastricht Radiat Oncol MaastRO Lab, GROW Sch Oncol & Dev Biol, NL-6200 MD Maastricht, Netherlands.
[Shiri-Sverdlov, Ronit] Maastricht Univ, Med Ctr, NUTRIM, Dept Mol Genet, NL-6200 MD Maastricht, Netherlands.
[Law, Betty Yuen Kwan; Liu, Liang; Wong, Vincent Kam Wai] Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Macau, Peoples R China.
[Chen, Yu-Jen] Mackay Mem Hosp, Dept Radiat Oncol, Taipei, Taiwan.
[Atkin, Julie D.; Sundaramoorthy, Vinod] Macquarie Univ, Dept Biomed Sci, Fac Med & Hlth Sci, Sydney, NSW 2109, Australia.
[Berliocchi, Laura] Magna Graecia Univ Catanzaro, Dept Hlth Sci, Catanzaro, Italy.
[Leardkamolkarn, Vijittra] Mahidol Univ, Dept Anat, Fac Sci, Bangkok 10700, Thailand.
[Sotthibundhu, Areechun] Thammasat Univ, Chulabhorn Int Coll Med, Pathum Thani, Thailand.
[Smith, Duncan R.] Mahidol Univ, Inst Mol Biosci, Salaya Campus, Nakhon Pathom, Thailand.
[Tan, Mei Lan] Malaysian Inst Pharmaceut & Nutraceuticals, George Town, Malaysia.
[Rudolf, Ruediger; Wild, Franziska] Mannheim Univ Appl Sci, Inst Mol & Cell Biol, Mannheim, Germany.
[Slaninova, Iva] Masaryk Univ, Dept Biol, Fac Med, Brno, Czech Republic.
[Costes, Safia; Mao, Kai] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Costes, Safia] Harvard Univ, Sch Med, Ctr Human Genet Res, Boston, MA USA.
[Costes, Safia] Dept Neurol, Boston, MA USA.
[Goruppi, Sandro; Lee, Sam W.; Tannous, Bakhos A.] Massachusetts Gen Hosp, Charlestown, MA USA.
[Goruppi, Sandro; Lee, Sam W.] Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA USA.
[Mao, Kai] Harvard Univ, Sch Med, Dept Mol Biol, Dept Genet, Boston, MA 02115 USA.
[Tannous, Bakhos A.] Harvard Univ, Sch Med, Expt Therapeut & Mol Imaging Lab, Neurosci Ctr, Charlestown, MA USA.
[Vyas, Jatin M.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Amon, Angelika; Santaguida, Stefano] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Graef, Martin; Motori, Elisa] Max Planck Inst Biol Ageing, Cologne, Germany.
[Storchova, Zuzana] Max Planck Inst Biochem, Grp Maintenance Genome Stabil, Klopferspitz 18A, D-82152 Martinsried, Germany.
[Wollert, Thomas] Max Planck Inst Biochem, Mol Membrane & Organelle Biol, Klopferspitz 18A, D-82152 Martinsried, Germany.
[Chowdhury, Kamal] Max Planck Inst Biophys Chem, Dept Mol Cell Biol, D-37077 Gottingen, Germany.
[Gassen, Nils Christian; Rein, Theo] Max Planck Inst Psychiat, Translat Res Psychiat, Munich, Germany.
[Schulze, Ryan J.] Mayo Clin, Dept Biochem, Rochester, MN USA.
[Fiesel, Fabienne C.; Springer, Wolfdieter] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA.
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[Fernandez-Zapico, Martin E.] Mayo Clin, Schulze Ctr Novel Therapeut, Div Oncol Res, Dept Oncol, Rochester, MN USA.
[Sacher, Michael] McGill Univ, Dept Anat & Cell Biol, Montreal, PQ, Canada.
[Shore, Gordon C.] McGill Univ, Dept Biochem, Montreal, PQ, Canada.
[Hussain, Sabah N. A.] McGill Univ, Dept Crit Care, Montreal, PQ, Canada.
[Li, Rui] McGill Univ, Dept Neurosci, Montreal Neurol Inst, Montreal, PQ, Canada.
[Maysinger, Dusica] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada.
[Pause, Arnim] McGill Univ, Goodman Canc Res Ctr, Montreal, PQ, Canada.
[Pause, Arnim] Dept Biochem, Montreal, PQ, Canada.
[Petrof, Basil J.] McGill Univ, Hlth Ctr Res Inst, Meakins Christie Labs, Montreal, PQ, Canada.
[Hussain, Sabah N. A.] McGill Univ, Ctr Hlth, Dept Med, Montreal, PQ, Canada.
[Poon, Audrey H.] McGill Univ, Hlth Ctr Res Inst, Meakins Christie Labs, Montreal, PQ, Canada.
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[Fon, Edward A.] McGill Univ, McGill Parkinson Program, Dept Neurol & Neurosurg, Montreal, PQ, Canada.
[Durcan, Thomas M.] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada.
[Bedard, Pierre-Andre] McMaster Univ, Dept Biol, Hamilton, ON, Canada.
[Sood, Anil K.; Wen, Yunfei] Univ Texas Houston, MD Anderson Canc Ctr, Dept Canc Biol, 1515 Holcombe Blvd, Houston, TX 77030 USA.
[Viale, Andrea] Univ Texas Houston, MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA.
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[Kern, Andreas] Johannes Gutenberg Univ Mainz, Med Ctr, D-55122 Mainz, Germany.
[Park, Jong-In] Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 USA.
[Teng, Ru-Jeng] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA.
[Amelio, Ivano] MRC, Toxicol Unit, Leicester, Leics, England.
[Behrends, Christian] Goethe Univ, Med Sch, Inst Biochem 2, Frankfurt, Germany.
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[Segatori, Laura] Rice Univ, Chem & Biomol Engn, Houston, TX USA.
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[Hamada, Kozo; Mikoshiba, Katsuhiko] RIKEN, Brain Sci Inst, Lab Dev Neurobiol, Saitama, Japan.
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[de Souza, Wanderley] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Rio De Janeiro, Brazil.
[Umekawa, Midori] Ritsumeikan Univ, Dept Biotechnol, Shiga, Japan.
[Flajolet, Marc] Rockefeller Univ, 1230 York Ave, New York, NY 10021 USA.
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[Greenwood, Michael T.] Royal Mil Coll Chem & Chem Engn, Kingston, ON, Canada.
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[Mihailidou, Anastasia Susie] Kolling Inst, Sydney, NSW, Australia.
[Platta, Harald W.] Ruhr Univ Bochum, Biochem Intrazellularer Transportprozesse, Univ Str 150, Bochum, Germany.
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[Xiao, Hengyi] Sichuan Univ, Aging Res Grp, State Key Lab Biotherapy, West China Hosp, Chengdu 610064, Peoples R China.
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[Akporiaye, Emmanuel T.] Sidra Med & Res Ctr, Doha, Qatar.
[Gorski, Sharon M.] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada.
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[Liu, Chun-Feng] Inst Neurosci, Suzhou, Peoples R China.
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[Galy, Vincent] Univ Paris 06, Sorbonne Univ, CNRS, UMR 7622,IBPS, Paris, France.
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[Husak, Zvenyslava] St Anna Kinderkrebsforschung, Childrens Canc Res Inst, Immunol Diagnost, Vienna, Austria.
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[Attardi, Laura D.] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
[Weyand, Cornelia M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Bai, Xue-Yuan; Chen, Xiangmei] Chinese Peoples Liberat Army Gen Hosp, Chinese PLA Inst Nephrol, State Key Lab Kidney Dis, Natl Clin Res Ctr Kidney Dis,Dept Nephrol, Beijing 100853, Peoples R China.
[Perl, Andras] SUNY Syracuse, Coll Med, Dept Med, Dept Microbiol & Immunol, Syracuse, NY USA.
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[Fingert, John H.] Stephen A Wynn Inst Vis Res, Iowa City, IA USA.
[Stroem, Anna-Lena] Stockholm Univ, Dept Neurochem, S-10691 Stockholm, Sweden.
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[Zeng, Jinsheng] Sun Yat Sen Univ, Dept Neurol, Guangzhou 510275, Guangdong, Peoples R China.
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[Lee, Myung-Shik] Yonsei Univ, Coll Med, Severans Biomed Sci Inst, Seoul 120749, South Korea.
[Lee, Myung-Shik] Dept Internal Med, Seoul, South Korea.
[Screaton, Robert A.] Sunnybrook Res Inst, Toronto, ON, Canada.
[Screaton, Robert A.] Univ Toronto, Dept Biochem, Toronto, ON, Canada.
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[Shih, Chwen-Ming] Taipei Med Univ, Dept Biochem, Coll Med, Taipei, Taiwan.
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[Biagosch, Caroline; Prokisch, Holger] Tech Univ Munich, Inst Human Genet, D-80290 Munich, Bavaria, Germany.
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[Roca, Gabriela] Tech Univ Carolo Wilhelmina Braunschweig, Biozentrum, D-38106 Braunschweig, Germany.
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[Alguel, Hana] Tech Univ Munich, Med Klin 2, Klinikum Rechts Isar, D-80290 Munich, Germany.
[Isono, Erika] Tech Univ Munich, Plant Syst Biol, D-80290 Freising Weihenstephan, Germany.
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Tel Aviv Univ, Dept Neurobiol, IL-69978 Tel Aviv, Israel.
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[Martinez-Outschoorn, Ubaldo] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Shapiro, Irving M.] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA.
[Ma, Zhenyi] Tianjin Med Univ, Dept Biochem & Mol Biol, Sch Basic Med Sci, Tianjin Key Lab Med Epigenet, Tianjin, Peoples R China.
[Liu, Zhe] Tianjin Med Univ, Dept Immunol, Tianjin Key Lab Med Epigenet, Tianjin, Peoples R China.
[Kong, Dexin] Tianjin Med Univ, Sch Pharmaceut Sci, Tianjin, Peoples R China.
[Nakano, Hiroyasu] Toho Univ, Sch Med, Dept Biochem, Tokyo, Japan.
[Fukuda, Mitsunori] Tohoku Univ, Dev Biol & Neurosci Dept, Grad Sch Life Sci, Sendai, Miyagi 980, Japan.
[Suzuki, Naoki] Tohoku Univ, Dept Neurol, Sendai, Miyagi 980, Japan.
[Kitajima, Yasuo] Tohoku Univ, Div Biomed Engn Hlth & Welf, Sendai, Miyagi 980, Japan.
[Ishida, Hiroyuki] Tohoku Univ, Grad Sch Agr Sci, Sendai, Miyagi 980, Japan.
[Arimoto, Hirokazu] Tohoku Univ, Grad Sch Life Sci, Sendai, Miyagi 980, Japan.
[Shintani, Takahiro] Tohoku Univ, Lab Bioind Gen, Grad Sch Agr Sci, Sendai, Miyagi 980, Japan.
[Kanno, Haruo] Tohoku Univ, Sch Med, Dept Orthopaed Surg, Sendai, Miyagi 980, Japan.
[Hadano, Shinji] Tokai Univ, Sch Med, Dept Mol Life Sci, Hiratsuka, Kanagawa 25912, Japan.
[Ohshima, Takayuki] Tokushima Bunri Univ, Fac Pharmaceut Sci, Kagawa Campus, Sanuki City, Kagawa, Japan.
[Saitoh, Tatsuya] Univ Tokushima, Div Mol Genet, Inst Enzyme Res, Kuramoto, Tokushima, Japan.
[Nagahara, Yukitoshi] Tokyo Denki Univ, Div Life Sci & Engn, Saitama, Japan.
[Sakoh-Nakatogawa, Machiko] Tokyo Inst Technol, Frontier Res Ctr, Yokohama, Kanagawa 227, Japan.
[Nakatogawa, Hitoshi] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Tokyo 152, Japan.
[Watase, Kei] Tokyo Med & Dent Univ, Ctr Brain Integrat Res, Bunkyo Ku, Tokyo, Japan.
[Oshima, Shigeru] Tokyo Med & Dent Univ, Dept Gastroenterol & Hepatol, Tokyo, Japan.
[Shimizu, Shigeomi] Tokyo Med & Dent Univ, Med Res Inst, Pathol Cell Biol, Tokyo, Japan.
[Abe, Akihisa; Miyazawa, Keisuke] Tokyo Med Univ, Dept Biochem, Tokyo 1608402, Japan.
[Tanaka, Keiji] Tokyo Metropolitan Inst Med Sci, Lab Prot Metab, Tokyo, Japan.
[Kuchitsu, Kazuyuki] Tokyo Univ Sci, Dept Appl Biol Sci, Noda, Chiba 278, Japan.
[Kuchitsu, Kazuyuki] Imaging Frontier Ctr, Noda, Chiba, Japan.
[Ichihara, Atsuhiro] Tokyo Womens Med Univ, Dept Endocrinol & Hypertens, Tokyo, Japan.
[Guo, Chuanyong] Tongji Univ, Sch Med, Dept Gastroenterol, Shanghai Peoples Hosp 10, Shanghai 200092, Peoples R China.
[Sun, Fang-Lin] Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China.
[Zacksenhaus, Eldad] Univ Hlth Network, Div Adv Diagnost, Toronto Gen Res Inst, Toronto, ON, Canada.
[Higaki, Katsumi] Tottori Univ, Res Ctr Biosci & Technol, Yonago, Tottori, Japan.
[Kalia, Manjula] Translat Hlth Sci & Technol Inst, Vaccine & Infect Dis Res Ctr, Faridabad, India.
[Lum, Julian J.] Trev & Joyce Deeley Res Ctr, Victoria, BC, Canada.
[Lum, Julian J.] Univ Victoria, BC Canc Agcy, Victoria, BC, Canada.
[Lum, Julian J.] Univ Victoria, Dept Biochem & Microbiol, Victoria, BC, Canada.
[Martin, Seamus J.] Trinity Coll Dublin, Dept Genet, Smurfit Inst, Dublin, Ireland.
[Murray, James T.] Trinity Coll Dublin, Sch Biochem & Immunol, Trinity Biomed Sci Inst, Dublin, Ireland.
[Campbell, Matthew] Trinity Coll Dublin, Smurfit Inst Genet, Dublin, Ireland.
[Chen, Ye-Guang; Liu, Yule; Wang, Yan] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China.
[Yu, Li] Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Tsing Hua Univ, Peking Univ,Joint Ctr Life Sci,Sch Life Sci, Beijing 100084, Peoples R China.
[Lei, Jinzhi] Tsinghua Univ, Zhou Pei Yuan Ctr Appl Math, Beijing 100084, Peoples R China.
[Taylor, Allen] Tufts Univ, USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Dash, Srikanta] Tulane Univ, Hlth Sci Ctr, Dept Pathol & Lab Med, New Orleans, LA 70118 USA.
[Simak, Jan] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
[Rao, V. Ashutosh] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Galadari, Sehamuddin] UAE Univ, Cell Signaling Lab, Dept Biochem, Coll Med & Hlth Sci, Abu Dhabi, U Arab Emirates.
[Bjedov, Ivana] UCL Canc Inst, London, England.
[Salomoni, Paolo] UCL Canc Inst, Samantha Dickson Brain Canc Unit, London, England.
[Jacques, Thomas S.] UCL Inst Child Hlth, London, England.
[Jacques, Thomas S.] Great Ormond St Hosp Children NHS Fdn Trust, London, England.
[Lewis, Patrick A.] UCL Inst Neurol, Dept Mol Neurosci, London, England.
[Manzoni, Claudia] UCL Inst Neurol, London, England.
[Cheetham, Michael E.] UCL Inst Ophthalmol, London, England.
[Guo, Ming] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA.
[Linden, Rafael] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Rio de Janeiro, Brazil.
[Simmet, Thomas] Univ Ulm, Inst Pharmacol Nat Cpds & Clin Pharmacol, D-89069 Ulm, Germany.
[Carlsson, Sven R.] Umea Univ, Dept Med Biochem & Biophys, Umea, Sweden.
[Kaeffer, Bertrand] UMR 1280, Nantes, France.
[Manie, Serge N.] CNRS, INSERM 1052, UMR 5286, Canc Res Ctr Lyon, Lyon, France.
[Maiuri, Maria Chiara] Ctr Rech Cordeliers, UMRS 1138, Paris, France.
[Gorbunov, Nikolai V.] Uniformed Serv Univ Hlth Sci, Dept Anesthesiol, Bethesda, MD 20814 USA.
[Kiang, Juliann G.] Uniformed Serv Univ Hlth Sci, Radiat Combined Injury Program, Armed Forces Radiobiol Res Inst, Bethesda, MD 20814 USA.
[Ozpolat, Bulent; Scovassi, A. Ivana; Stellrecht, Christine M.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA.
[Gonzalez, Carlos B.] Univ Austral Chile, Dept Physiol, Valdivia, Chile.
[Diaz-Nido, Javier] Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, CIBERER, Madrid, Spain.
[Gargini, Ricardo] Univ Autonoma Madrid, CNB CSIC, Ctr Biol Mol Severo Ochoa, Dept Biol Mol, Madrid, Spain.
[Cuezva, Jose M.] Univ Autonoma Madrid, Dept Biol Mol, Madrid, Spain.
[Magarinos, Marta] Univ Autonoma Madrid, Dept Biol, Madrid, Spain.
[Guillen, Carlos] Univ Complutense, Sch Pharm, E-28040 Madrid, Spain.
[Guillen, Carlos] Inst Salud Carlos III, CIBER Diabet & Enfermedades Metab Olicas Asociada, Madrid, Spain.
[Papademetrio, Daniela L.] Univ Buenos Aires, Inmunol, Fac Farm & Bioquim, Buenos Aires, DF, Argentina.
[Cena, Valentin] Univ Castilla La Mancha, Albacete, Spain.
[Jordan, Joaquin] Univ Castilla La Mancha, Fac Med, Dept Ciencias Med, Albacete, Spain.
[Sanchez-Prieto, Ricardo] Univ Castilla La Mancha, Lab Oncol Mol, Ctr Reg Invest Biomed, Albacete, Spain.
[Troncoso, Rodrigo] Univ Chile, Adv Ctr Chron Dis ACCDiS, Fac Ciencias Quim & Farmaceut, Santiago, Chile.
[Chiong, Mario; Criollo, Alfredo; Lavandero, Sergio] Univ Chile, Adv Ctr Chron Dis ACCDiS, Santiago, Chile.
[Diaz-Araya, Guillermo] Univ Chile, Fac Ciencias Quim & Farmaceut, Santiago, Chile.
[Glavic, Alvaro] Univ Chile, Fac Ciencias, Dept Biol, Ctr Regulac Genoma, Santiago, Chile.
[Troncoso, Rodrigo] Univ Chile, INTA, Santiago, Chile.
[Corral-Ramos, Cristina; Di Pietro, Antonio; Roncero, M. Isabel G.; Ruiz-Roldan, Carmen] Univ Cordoba, Campus Excelencia Agroalimentario CeiA3, Dept Genet, Cordoba, Spain.
[Mora-Rodriguez, Rodrigo] Univ Costa Rica, CIET, San Jose, Costa Rica.
[Fuentes, Jose M.; Gomez-Sanchez, Ruben; Ana Gonzalez-Polo, Rosa; Niso-Santano, Mireia] Univ Extremadura, CIBERNED, Dept Bioquim & Biol Mol & Genent, Fac Enfermeria & Terapia Ocupac, Caceres, Spain.
[Fernandez-Lopez, Arsenio; Perez-Rodriguez, Diego] Univ Leon, Area Biol Celular, Inst Biomed, E-24071 Leon, Spain.
[Fernandez-Barrena, Maite G.] Univ Navarra, Ctr Invest Med Aplicada, E-31080 Pamplona, Spain.
[Albaiceta, Guillermo M.] Univ Oviedo, Dept Biol Func, Oviedo, Spain.
[Fernandez, Alvaro F.; Lopez-Otin, Carlos] Univ Oviedo, Inst Univ Oncol, Dept Bioquim & Biol Mol, Oviedo, Spain.
[Jimenez, Alberto] Univ Salamanca, Dept Microbiol & Genet, Campus Miguel Unamuno, E-37008 Salamanca, Spain.
[Boada-Romero, Emilio; Pimentel-Muinos, Felipe X.] Univ Salamanca, IBMCC, Ctr Invest Canc, Campus Unamuno, Salamanca, Spain.
[Miranda-Vizuete, Antonio] Univ Seville, Inst Biomed Sevilla, Hosp Univ Virgen Rocio, Consejo Super Invest Cient, Seville, Spain.
[Ruano, Diego] Univ Seville, Inst Biomed Sevilla, Seville, Spain.
[Crespo, Jose L.; Esther Perez-Perez, Maria] Univ Seville, CSIC, Inst Bioquim Vegetal & Fotosintesis, Seville, Spain.
[Couve, Eduardo] Univ Valparaiso, Inst Biol, Fac Ciencias, Valparaiso, Chile.
[Pardo, Julian] Univ Zaragoza Araid, IIS Aragon, Ctr Invest Biomed Aragon, Zaragoza, Spain.
[Filippi-Chiela, Eduardo C.; Lenz, Guido; Thome, Marcos P.] Univ Fed Rio Grande do Sul, Dept Biophys, Porto Alegre, RS, Brazil.
[Filippi-Chiela, Eduardo C.; Lenz, Guido; Thome, Marcos P.] Ctr Biotechnol, Porto Alegre, RS, Brazil.
[Silvia Romano, Patricia] Univ Nacl Cuyo FCM UNCUYO, Inst Histol & Embriol IHEM CONICET, Fac Ciencias Med, Mendoza, Argentina.
[Sanchez-Alcazar, Jose A.] Univ Pablo Olavide, CABD, Consejo Super Invest Cient Junta Andalucia, Seville, Spain.
[Weis, Simone Nardin] Univ Brasilia, Dept Biol Celular, Brasilia, DF, Brazil.
[Rodrigues, Cecilia M. P.] Univ Lisbon, Res Inst Med iMed ULisboa, Fac Pharm, Lisbon, Portugal.
[Botana, Luis M.] Univ Santiago Compostela, Dept Farmacol, Fac Vet, Lugo, Spain.
[Goldman, Gustavo H.] Univ Sao Paulo, FCFRP, USP, Sao Paulo, Brazil.
[Hernandez, Agustin] Univ Sao Paulo, Dept Parasitol, Inst Ciencias Biomed, Sao Paulo, Brazil.
[Brito, Glauber C.] Univ Sao Paulo, Inst Canc Estado Sao Paulo, Fac Med, Sao Paulo, SP, Brazil.
[Tenorio de Melo, Edesio Jose] Univ Estadual Norte Fluminense, Ctr Biociencias Biotecnol, Lab Biol Celular & Tecidual, Setor Toxicol Celular, Campos Goytacazes, Rio De Janeiro, Brazil.
[Rizzo, Elizete] Univ Fed Minas Gerais, Dept Morfol, Inst Ciencias Biol, Belo Horizonte, MG, Brazil.
[Bincoletto, Claudia] Univ Fed Sao Paulo UNIFESP, Dept Farmacol, Escola Paulista Med, Sao Paulo, SP, Brazil.
[Vieira, Helena L. A.] Univ Nova Lisboa, CEDOC, NOVA Med Sch, Lisbon, Portugal.
[Revuelta, Jose L.] Univ Salamanca, Dept Microbiol & Genet, Campus Miguel Unamuno, E-37008 Salamanca, Spain.
[Poletti, Angelo; Rusmini, Paola] Univ Milan, Dipartimento Sci Farmacol & Biomol, Milan, Italy.
[Carra, Serena] Univ Modena & Reggio Emilia, Dipartimento Sci Biomed Metab & Neurosci, Modena, Italy.
[Follo, Carlo; Isidoro, Ciro] Univ Piemonte Orientale, Dipartimento Sci Salute, Novara, Italy.
[Genazzani, Armando A.] Univ Piemonte Orientale, Novara, Italy.
[Matarese, Giuseppe] Univ Salerno, Dipartimento Med & Chirurg, I-84100 Salerno, Italy.
[Rippo, Maria Rita] Univ Politecn Marche, Dept Clin & Mol Sci, Ancona, Italy.
[Cenci, Simone; Milan, Enrico] Univ Vita Salute San Raffaele, Milan, Italy.
[Casas, Caty] Univ Autonoma Barcelona, Dept Cell Biol Physiol & Immunol, Inst Neurociencies, E-08193 Barcelona, Spain.
[Ventura, Salvador] Autonomous Univ Barcelona, Inst Biotecnol & Biomed, Bellaterra, Barcelona, Spain.
[Ventura, Salvador] Dept Bioquim & Biol Mol, Bellaterra, Barcelona, Spain.
[Zorzano, Antonio] Univ Barcelona, Dept Bioquim & Biol Mol, Fac Biol, Barcelona, Spain.
[Luis Rosa, Jose] Univ Barcelona, Hosp Llobregat, Dept Ciencies Fisiol Giques 2, Inst Invest Biomed Bellvitge IDI BELL, Campus Bellvitge, Barcelona, Spain.
[Segui-Simarro, Jose M.] Univ Politecn Valencia, COMAV Inst, E-46022 Valencia, Spain.
[Reichert, Andreas S.] Univ Klinikum Dusseldorf, Inst Biochem & Mol Biol 1, Dusseldorf, Germany.
[Bouchecareilh, Marion; Priault, Muriel] Univ Bordeaux Segalen, Inst Biochim & Genet Cellulaires, CNRS, UMR 5095, Bordeaux, France.
[Pasquet, Jean-Max] Univ Bordeaux Segalen, INSERM U1035, Hematopoiese Leucem & Cibles Therapeut, Bordeaux, France.
[Duvezin-Caubet, Stephane] Univ Bordeaux, Inst Biochim & Genet Cellulaires, CNRS, UMR 5095, Bordeaux, France.
[Lapaquette, Pierre] Univ Bourgogne Franche Comte, Agrosup Dijon, UMR PAM, Equipe Vin Aliment Microbiol, Dijon, France.
[Feron, Olivier] Catholic Univ Louvain, IREC, B-1200 Brussels, Belgium.
[Batoko, Henri] Catholic Univ Louvain, Inst Sci Vie, Louvain La Neuve, Belgium.
[Deldicque, Louise] Catholic Univ Louvain, Inst Neurosci, Louvain La Neuve, Belgium.
[Gailly, Philippe] Catholic Univ Louvain, Lab Cell Physiol, B-1200 Brussels, Belgium.
[Bruhat, Alain] Univ Clermont 1, UFR Med, Nutr Humaine UMR1019, Clermont Ferrand, France.
[Dalmasso, Guillaume; Darfeuille-Michaud, Arlette; Nguyen, Hang T. T.] Univ Auvergne, M2iSH, INSERM UMR 1071, Ctr Biomed Rech & Valorisat,Fac Med, Clermont Ferrand, France.
[Djavaheri-Mergny, Mojgan] Univ Bordeaux, INSERM U916, Inst Bergonie, Bordeaux, France.
[Dehay, Benjamin] Univ Bordeaux, Inst Malad Neurodegenerat, CNRS UMR 5293, Bordeaux, France.
[Camougrand, Nadine] Univ Bordeaux, CNRS, Inst Biochim & Genet Cellulaires, UMR 5095, Bordeaux, France.
[Delage-Mourroux, Regis] Univ Franche Comte, UFR Sci & Tech EA3922, SFR IBCT FED 4234, Estrogenes Express Genique & Pathol Syst Nerveux, Besancon, France.
[Boyer-Guittaut, Michaeel] Univ Franche Comte, UFR Sci & Tech, Lab Biochim, Besancon, France.
[Verdier, Mireille] Univ Limoges, EA 3842, LHCP, Fac Med, Limoges, France.
[Kretz-Remy, Carole] Univ Lyon, Lyon, France.
[Kretz-Remy, Carole] Univ Lyon 1, Ctr Genet & Physiol Mol & Cellulaire, F-69622 Villeurbanne, France.
[Freyssenet, Damien G.] Univ Lyon, Fac Med, Saint Etienne, France.
[Faure, Mathias] Univ Lyon, INSERM, CIRI, Ecole Normale Super Lyon,CNRS,UMR 5308,U 111, Lyon, France.
[Mollereau, Bertrand] Univ Lyon, CNRS UMR 5239, Mol Cell Biol Lab, Ecole Normale Super Lyon, Lyon, France.
[Besteiro, Sebastien] Univ Montpellier, DIMNP, CNRS, UMR 5235, F-34059 Montpellier, France.
[Pattingre, Sophie] Univ Montpellier, Inst Reg Canc Montpellier, INSERM, U 1194, F-34059 Montpellier, France.
[Favier, Francois B.] Univ Montpellier, F-34059 Montpellier, France.
[Bernard, Monique; Hebert, Marie-Josee] Univ Montreal, Dept Med, Montreal, PQ, Canada.
[Pacelli, Consiglia] Univ Montreal, Dept Pharmacol, Fac Med, Montreal, PQ H3C 3J7, Canada.
[Burelle, Yan] Univ Montreal, Fac Pharm, Montreal, PQ H3C 3J7, Canada.
[Knaevelsrud, Helene] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada.
[Vallette, Francois] Univ Nantes, CRCNA, UMRINSERM 892, CNRS 6299, Nantes, France.
[Chevet, Eric] Univ Rennes 1, OSS, ERL INSERM 440, Ctr Lutte Canc Eugene Marquis, Rennes, France.
[Beaulieu, Jean-Francois; Jean, Steve] Univ Sherbrooke, Dept Anat & Cell Biol, Fac Med & Hlth Sci, Sherbrooke, PQ J1K 2R1, Canada.
[Dupuis, Luc] Univ Strasbourg, Fac Med, UMRS 1118, Strasbourg, France.
[Gros, Frederic] Univ Strasbourg, CNRS UPR3572, Immunopathol & Chim Therapeut, IBMC, Strasbourg, France.
[Barbeau, Benoit] Univ Quebec, Dept Sci Biol, Montreal, PQ H3C 3P8, Canada.
[Barbeau, Benoit] Ctr Rech BioMed, Montreal, PQ, Canada.
[Taillebourg, Emmanuel] Univ Grenoble Alpes, CEA DSV iRTSV BGE GenandChem, INSERM, U1038, Grenoble, France.
[Francois, Arnaud] Univ Laval, Neurosci Axis, Quebec City, PQ, Canada.
[Cnop, Miriam] Univ Libre Bruxelles, ULB Ctr Diabet Res, Brussels, Belgium.
[Palladino, Francesca] Univ Lyon, Ecole Normale Super Lyon, Lyon, France.
[Baghdiguian, Stephen] Univ Montpellier 2, Inst Sci Evolut, CNRS, UMR 5554, Montpellier, Languedoc Rouss, France.
[Pierrefite-Carle, Valerie] Univ Nice Sophia Antipolis, UMR MATOs CEA iBEB E 4320TIRO, Fac Med, Nice, France.
[Kroemer, Guido] Univ Paris 05, Apoptosis Canc & Immun Lab, Team 11, Equipe Labellisee Ligue Canc & Cell Biol & Met Pl, Paris, France.
[Tamburini, Jerome] Univ Paris 05, Inst Cochin, Sorbonne Paris Cite, Fac Med, Paris, France.
[Pende, Mario] Univ Paris 05, Inst Necker Enfants Malades, INSERM, U1151, Paris, France.
[Rautou, Pierre-Emmanuel] Univ Paris 05, Paris, France.
[Bravo-San Pedro, Jose M.; Galluzzi, Lorenzo; Izzo, Valentina; Pietrocola, Federico; Sica, Valentina] Univ Paris Descartes Paris V, Paris, France.
[Botti, Joelle; Codogno, Patrice; Dupont, Nicolas; Hamai, Ahmed; Mehrpour, Maryam; Morel, Etienne; Nascimbeni, Anna Chiara; Orhon, Idil] Univ Paris 05, Sorbonne Paris Cite, INEM, INSERM U1151,CNRS UMR 5253, Paris, France.
[Ait-Si-Ali, Slimane] Univ Paris 05, Sorbonne Paris Cite, Ctr Epigenet & Destin Cellulaire, CNRS,UMR 7216, Paris, France.
[Le Stunff, Herve] Univ Paris 05, Unite Biol Fonctionnelle & Adaptat, CNRS UMR 8251, Paris, France.
[Bianchi, Michele Wolfe] Univ Paris Est Creteil, Creteil, France.
[Teixeira-Clerc, Fatima] Univ Paris Est, Inst Mondor Rech Biomed, Paris, France.
[Le Stunff, Herve; Legouis, Renaud] Univ Paris Sud, CEA, CNRS, Inst Integrat Biol Cell, Gif Sur Yvette, France.
[Bianchi, Michele Wolfe] Univ Paris Sud, CEA, CNRS, Paris, France.
[Deutsch, Eric] Univ Paris Sud, INSERM 1030, Gustave Roussy Canc Campus, Paris, France.
[Dokudovskaya, Svetlana] Univ Paris Sud, Inst Gustave Roussy, CNRS UMR 8126, Villejuif, France.
[Wiels, Joelle] Univ Paris Sud, Univ Paris Saclay, CNRS UMR 8126, Inst Gustave Roussy, Villejuif, France.
[Tan, Mei Lan] Univ Sains Malaysia, Adv Med & Dent Inst, Minist Sci Technol & Innovat, George Town, Malaysia.
[D'Orazi, Gabriella] Univ G dAnnunzio, Dept Med Oral & Biotechnol Sci, Chieti, Italy.
[Corasaniti, Maria Tiziana] Magna Graecia Univ Catanzaro, Dept Hlth Sci, Catanzaro, Italy.
[Isakovic, Aleksandra J.] Univ Belgrade, Sch Med, Belgrade, Serbia.
[Lizard, Gerard] Univ Bourgogne Franche Comte, EA 7270, INSERM, Dijon, France.
[Fortunato, Franco] Univ Clin Heidelberg, Dept Expt Surg, Heidelberg, Germany.
[Rami, Abdelhaq] Univ Clin, Inst Cellular & Mol Anat Anat 3, Frankfurt, Germany.
[McKenna, Sharon; O'Donovan, Tracey] Natl Univ Ireland Univ Coll Cork, BioSci Inst Co, Cork Canc Res Ctr, Cork, Ireland.
[Waeber, Christian] Natl Univ Ireland Univ Coll Cork, Sch Pharm, Dept Pharmacol & Therapeut, Cork, Ireland.
[Al-Rubeai, Mohamed] Univ Coll Dublin, Sch Chem & Bioproc Engn, Dublin 2, Ireland.
[Alvarez-Erviti, Lydia; Cooper, J. Mark] UCL, Dept Clin Neurosci, London, England.
[Ketteler, Robin; Kriston-Vizi, Janos; Prak, Krisna] UCL, MRC Lab Mol Cell Biol, London, England.
[Duchen, Michael R.] UCL, UCL Consortium Mitochondrial Res, London, England.
[Duchen, Michael R.] Dept Cell & Dev Biol, London, England.
[Clementi, Emilio] Univ Milan, Univ Hosp Luigi Sacco, Clin Pharmacol Unit, Natl Res Council,Inst Neurosci,Dept Biomed & Clin, Milan, Italy.
[Strnad, Pavel] Univ Hosp Aachen, IZKF, Aachen, Germany.
[Strnad, Pavel] Dept Internal Med III, Aachen, Germany.
[Puyal, Julien; Truttmann, Anita C.] Univ Lausanne, Univ Hosp Ctr, Clin Neonatol, Dept Pediat & Pediat Surg, Lausanne, Switzerland.
[Bergami, Matteo] Univ Hosp Cologne, CECAD Res Ctr, Cologne, Germany.
[Klucken, Jochen; Minakaki, Georgia] Univ Erlangen Nurnberg, Univ Hosp Erlangen, D-91054 Erlangen, Germany.
[Hasselblatt, Peter] Univ Hosp Freiburg, Dept Med 2, Freiburg, Germany.
[Dahmen, Uta] Univ Hosp Jena, Dept Gen Visceral & Vasc Surg, Expt Transplantat Surg, Jena, Germany.
[Bou, German] Univ Hosp La Coruna, Dept Microbiol, La Coruna, Spain.
[Pavenstaedt, Hermann] Univ Hosp Muenster, Internal Med D, Dept Nephrol Hypertens & Rheumatol, Albert Schweitzer Campus, Munster, Germany.
[Patschan, Daniel] Univ Hosp Gottingen, Dept Nephrol & Rheumatol, Gottingen, Germany.
[Duchosal, Michel A.] Univ Hosp Lausanne, Serv & Cent Lab Hematol, Lausanne, Switzerland.
[Weide, Thomas] Univ Hosp Muenster, Dept Internal Med D, Mol Nephrol, Munster, Germany.
[Schneider, E. Marion] Univ Hosp Ulm, Sekt Expt Anaestesiol, Ulm, Germany.
[Scharl, Michael] Univ Hosp Zurich, Div Gastroenterol & Hepatolog, Zurich, Switzerland.
[Decuypere, Jean-Paul] Univ Hosp Leuven, Dept Microbiol & Immunol, Lab Abdominal Transplantat, Leuven, Belgium.
[Vandenberghe, Wim] Univ Hosp Leuven, Dept Neurol, Leuven, Belgium.
[Martinez, Jennifer] Natl Inst Environm Hlth Sci, Immun Inflammat & Dis Lab, Res Triangle Pk, NC USA.
[Duez, Helene; Lancel, Steve] Univ Lille, INSERM, CHU Lille, Inst Pasteur Lille,U1011,EGID, Lille, France.
[Huber, Tobias B.] Univ Med Ctr Freiburg, Freiburg, Germany.
[Vellenga, Edo] Univ Groningen, Univ Med Ctr Groningen, Dept Hematol, Groningen, Netherlands.
[Galliciotti, Giovanna] Univ Hamburg, Med Ctr, Inst Neuropathol, Hamburg, Germany.
[Behl, Christian] Johannes Gutenberg Univ Mainz, Med Ctr, Inst Pathobiochemi, D-55122 Mainz, Germany.
[Mari, Muriel; Reggiori, Fulvio] Univ Groningen, Univ Med Ctr Groningen, Dept Cell Biol, Groningen, Netherlands.
[Schmidt, Jens] Univ Gottingen, Med Ctr, Clin Neurol, D-37073 Gottingen, Germany.
[Schmidt, Jens] Dept Neuroimmunol, Gottingen, Germany.
[Outeiro, Tiago F.] Univ Gottingen, Med Ctr, Dept Neurodegenerat & Restorat Res, D-37073 Gottingen, Germany.
[Boes, Marianne] Univ Utrecht, Med Ctr, Lab Translat Immunol, Utrecht, Netherlands.
[Boes, Marianne] Univ Hosp Children & Youth, Dept Pediat Immunol, Utrecht, Netherlands.
[Koch, Jan C.] Univ Med Gottingen, Dept Neurol, Gottingen, Germany.
[Wang, Jing] Univ Montpellier I, INSERM U1051, Montpellier, France.
[Vidal, Michel] Univ Montpellier, UMR5235, F-34059 Montpellier, France.
[Coxon, Fraser P.] Univ Aberdeen, Div Appl Med, Aberdeen, Scotland.
[Ganesan, Swamynathan] Univ Adelaide, Alzheimers Dis Genet Lab, Adelaide, SA, Australia.
[Richards, Robert I.] Univ Adelaide, Dept Genet & Evolut, Sch Biol Sci, Adelaide, SA, Australia.
[Ramanadham, Sasanka] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol CDIB, Comprehens Diabet Ctr UCDC, Birmingham, AL USA.
[Xu, Zhi-Xiang] Univ Alabama Birmingham, Dept Med, Div Hematol & Oncol, Ctr Comprehens Canc, Birmingham, AL 35294 USA.
[Roth, Kevin A.; Shacka, John J.; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA.
[Darley-Usmar, Victor M.] Univ Alabama Birmingham, Dept Pathol, Ctr Free Radical Biol, Birmingham, AL 35294 USA.
[Chatham, John C.] Univ Alabama Birmingham, Div Mol & Cellular Pathol, Dept Pathol, Birmingham, AL USA.
[Kim, Yonghyun] Univ Alabama, Dept Chem & Biol Engn, Tuscaloosa, AL USA.
[Goping, Ing Swie] Univ Alberta, Dept Biochem, Edmonton, AB, Canada.
[Diaz-Laviada, Ines] Univ Alcala De Henares, Dept Syst Biol, Biochem & Mol Biol Unit, Sch Med, Madrid, Spain.
[Medema, Jan Paul] Univ Amsterdam, Acad Med Ctr, Lab Expt Oncol & Radiobiol, Meibergdreef 9, NL-1105 AZ Amsterdam, North Holland, Netherlands.
[Juenemann, Katrin] Univ Amsterdam, Acad Med Ctr, Dept Cellbiol & Histol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
[Meijer, Alfred J.] Univ Amsterdam, Acad Med Ctr, Dept Med Biochem, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
[Berkhout, Ben] Univ Amsterdam, Acad Med Ctr, Lab Expt Virol, Ctr Infect & Immun Amsterdam CINIMA, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
[Norga, Koenraad K.] Univ Antwerp, Dept Paediat Oncol, B-2020 Antwerp, Belgium.
[De Meyer, Guido R. Y.; Martinet, Wim] Univ Antwerp, Lab Physiopharmacol, B-2020 Antwerp, Belgium.
[Landowski, Terry H.] Univ Arizona, Ctr Canc, Dept Med, Tucson, AZ USA.
[Kruer, Michael C.] Univ Arizona, Coll Med, Barrow Neurol Inst, Phoenix Childrens Hosp,Dept Child Hlth, Phoenix, AZ USA.
[Riehle, Michael A.] Univ Arizona, Dept Entomol, Tucson, AZ USA.
[Chen, Yin; Klimecki, Walter T.; Zhang, Donna D.] Univ Arizona, Dept Pharmacol & Toxicol, Coll Pharm, Tucson, AZ 85721 USA.
[Ding, Zufeng; Mehta, Jawahar L.] Univ Arkansas Med Sci, Dept Cardiol, Little Rock, AR 72205 USA.
[Voth, Daniel E.] Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA.
[MacMillan-Crow, Lee Ann; Parajuli, Nirmala] Univ Arkansas Med Sci, Dept Pharmacol Toxicol, Little Rock, AR 72205 USA.
[Dridi, Sami] Univ Arkansas, Ctr Excellence Poultry Sci, Fayetteville, AR 72701 USA.
[Konstantakou, Eumorphia G.; Stravopodis, Dimitrios J.; Trougakos, Ioannis P.; Velentzas, Athanassios D.] Univ Athens, Dept Cell Biol & Biophys, Fac Biol, Athens, Greece.
[Mpakou, Vassiliki E.] Univ Athens, Sch Med, Dept Internal Med 2, Athens, Greece.
[Mpakou, Vassiliki E.] Attikon Univ, Gen Hosp, Res Inst, Athens, Greece.
[Kampinga, Harm H.] Univ Groningen, Univ Med Ctr Groningen, Dept Cell Biol, Groningen, Netherlands.
[Pierre, Philippe] Univ Aveiro, Inst Res Biomed iBiMED, Aveiro Hlth Sci Program, Aveiro, Portugal.
[Neves, Bruno M.] Univ Aveiro QOPNA, Dept Chem, Aveiro, Portugal.
[Claria, Joan; Lopez-Vicario, Cristina] Univ Barcelona, Dept Biochem & Mol Genet, Hosp Clin, IDIBAPS CIBERehd, Barcelona, Spain.
[Ambrosio, Santiago] Univ Barcelona, Sch Med, Campus Bellvitge, Lhospitalet De Llobregat, Spain.
[Cocco, Tiziana] Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Organs Senses, Bari, Italy.
[Tucci, Marco] Univ Bari Aldo Moro, Dept Biomed Sci & Clin Oncol, Bari, Italy.
[Simone, Cristiano] Univ Bari Aldo Moro, Div Med Genet, DIMO, Sch Med, Bari, Italy.
[Castets, Perrine; Ruegg, Markus A.; Spang, Anne] Univ Basel, Biozentrum, Basel, BS, Switzerland.
[Boeckler, Stefan; Westermann, Benedikt] Univ Bayreuth, Cell Biol, Bayreuth, Germany.
[Steegborn, Clemens] Univ Bayreuth, Dept Biochem, Bayreuth, Germany.
[Harhaji-Trajkovic, Ljubica] Univ Belgrade, Inst Biol Res Sinisa Stankov, Belgrade, Serbia.
[Kravic-Stevovic, Tamara] Univ Belgrade, Inst Histol & Embryol, Sch Med, Belgrade, Serbia.
[Markovic, Ivanka] Univ Belgrade, Inst Med & Clin Biochem, Fac Med, Belgrade, Serbia.
[Trajkovic, Vladimir] Univ Belgrade, Sch Med, Belgrade, Serbia.
[Bumbasirevic, Vladimir] Univ Belgrade, Sch Med, Inst Histol & Embryol, Belgrade, Serbia.
[Tschan, Mario P.] Univ Bern, Div Expt Pathol, Inst Pathol, Bern, Switzerland.
[Arcaro, Alexandre] Univ Bern, Div Pediat Hematol Oncol, Dept Clin Res, Bern, Switzerland.
[Buetikofer, Peter] Univ Bern, Inst Biochem & Mol Med, Bern, Switzerland.
[Simon, Hans-Uwe] Univ Bern, Inst Pharmacol, Bern, Switzerland.
[Sarkar, Sovan; Ward, Carl] Univ Birmingham, Inst Biomed Res, Inst Canc & Genom Sci, Coll Med & Dent Sci, Birmingham, W Midlands, England.
[Taylor, Graham S.] Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham, W Midlands, England.
[Martelli, Alberto M.] Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, Italy.
[Cetrullo, Silvia; Flamigni, Flavio] Univ Bologna, Dipartimento Sci Biomed & Neuromotorie, Bologna, Italy.
[Walter, Jochen] Univ Bonn, Dept Neurol, Bonn, Germany.
[Haas, Albert; Hoehfeld, Joerg] Univ Bonn, Inst Cell Biol, Bonn, Germany.
[Till, Andreas] Univ Bonn, Inst Reconstruct Neurobiol, Bonn, Germany.
[Fanzani, Alessandro] Univ Brescia, Dept Mol & Translat Med, Brescia, Italy.
[Lane, Jon D.] Univ Bristol, Sch Biochem, Bristol, Avon, England.
[Greenhough, Alexander] Univ Bristol, Sch Cellular & Mol Med, Bristol, Avon, England.
[Roberge, Michel; Yip, Calvin K.] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V5Z 1M9, Canada.
[Johnson, James D.; Nabi, Ivan R.] Univ British Columbia, Dept Cellular & Physiol Sci, Vancouver, BC V5Z 1M9, Canada.
[Wang, Yu Tian] Univ British Columbia, Dept Med, Vancouver, BC V5Z 1M9, Canada.
[Wang, Yu Tian] Brain Res Ctr, Vancouver, BC, Canada.
[Luo, Honglin] Univ British Columbia, Dept Pathol & Lab Med, James Hogg Res Ctr, Vancouver, BC V5Z 1M9, Canada.
[Shi, Junyan] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada.
[Toker, Lilach] Univ British Columbia, Dept Psychiat, Vancouver, BC V5Z 1M9, Canada.
[Gleave, Martin] Univ British Columbia, Dept Urol Sci, Vancouver, BC V5Z 1M9, Canada.
[Jiang, Xiaoyan] Univ British Columbia, Med Genet & BC Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1M9, Canada.
[Piret, James M.] Univ British Columbia, Michael Smith Labs, Dept Chem & Biol Engn, Vancouver, BC V5Z 1M9, Canada.
[Turner, Robin F. B.] Univ British Columbia, Michael Smith Labs, Vancouver, BC V5Z 1M9, Canada.
[Blanco, Guillermo A.] Univ Buenos Aires, IDEHU CONICET, Fac Pharm & Biochem, Buenos Aires, DF, Argentina.
[Alvarez, Silvia] Univ Buenos Aires, Inst Biochem & Biophys, Sch Pharm & Biochem, Buenos Aires, DF, Argentina.
[Vaccaro, Maria I.] Univ Buenos Aires, Natl Council Sci & Tech Res CONICET, Inst Biochem & Mol Med, Dept Pathophysiol,Sch Pharm & Biochem, Buenos Aires, DF, Argentina.
[Perrotta, Ida] Univ Calabria, Dept Biol Ecol & Earth Sci, Lab Electron Microscopy, I-87036 Cosenza, Italy.
[Aquila, Saveria] Univ Calabria, Dept Pharm Hlth & Nutrit Sci, I-87036 Cosenza, Italy.
[Russo, Rossella] Univ Calabria, Dept Pharm Hlth & Nutrit Sci, Sect Preclin & Translat Pharmacol, I-87036 Cosenza, Italy.
[Chakrabarti, Gopal] Univ Calcutta, Dept Biotechnol, Dr BC Guha Ctr Genet Engn & Biotechnol, Kolkata, WB, India.
[Zheng, Xi-Long] Univ Calgary, Dept Biochem & Mol Biol, Libin Cardiovasc Inst Alberta, Calgary, AB, Canada.
[Schatzl, Hermann M.] Univ Calgary, Fac Vet Med, Calgary, AB, Canada.
[Hurley, James H.; Thorner, Jeremy] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
[Ge, Liang; Schekman, Randy] Univ Calif Berkeley, Howard Hughes Med Inst, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
[Kung, Hsing-Jien] Univ Calif Davis, Ctr Canc, Davis, CA 95616 USA.
[Luckhart, Shirley; Pakpour, Nazzy] Univ Calif Davis, Dept Med Microbiol & Immunol, Sch Med, Davis, CA 95616 USA.
[Powers, Ted] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA.
[Gomes, Aldrin V.] Univ Calif Davis, Dept Neurobiol Physiol & Behav, Davis, CA 95616 USA.
[Dinesh-Kumar, Savithrama P.] Univ Calif Davis, Dept Plant Biol, Davis, CA 95616 USA.
[Dinesh-Kumar, Savithrama P.] Coll Biol Sci, Genome Ctr, Davis, CA USA.
[van Doorn, Wouter G.] Univ Calif Davis, Mann Lab, Dept Plant Sci, Davis, CA 95616 USA.
[Edinger, Aimee L.] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92717 USA.
[Chen, Jeff W.] Univ Calif Irvine, Dept Neurosurg, Irvine, CA USA.
[Steffan, Joan] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA.
[Ganesan, Anand K.] Univ Calif Irvine, Irvine, CA USA.
[Xia, Tian] Univ Calif Los Angeles, Dept Med, Los Angeles, CA USA.
[Costes, Safia] Univ Calif Los Angeles, David Geffen Sch Med, Larry Hillblom Islet Res Ctr, Los Angeles, CA 90095 USA.
[Le Roch, Karine G.] Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA.
[Steele, John W.] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
[Lee, Jongdae; Satriano, Joseph] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
[Sigurdson, Christina J.] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA.
[Spector, Stephen A.] Univ Calif San Diego, Dept Pediat Div Infect Dis, La Jolla, CA 92093 USA.
[Campbell, Grant R.; Ordonez, Paulina] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.
[Guan, Kun-Liang] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.
[Guan, Kun-Liang] Moores Canc Ctr, La Jolla, CA USA.
[Miyamoto, Shigeki] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.
[La Spada, Albert R.] Univ Calif San Diego, Dept Cellular & Mol Med, Div Biol Sci, Inst Genom Med, La Jolla, CA 92093 USA.
[La Spada, Albert R.] Univ Calif San Diego, Dept Neurosci, Div Biol Sci, Inst Genom Med, La Jolla, CA 92093 USA.
[La Spada, Albert R.] Univ Calif San Diego, Dept Pediat, Div Biol Sci, Inst Genom Med, La Jolla, CA 92093 USA.
[Kiger, Amy A.] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
[Liu, Jing-Jing; Nazarko, Taras Y.] Univ Calif San Diego, Div Biol Sci, Mol Biol Sect, La Jolla, CA 92093 USA.
[Till, Andreas] Univ Calif San Diego, San Diego Ctr Syst Biol, La Jolla, CA 92093 USA.
[Cohen, Ezra E. W.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
[Soontornniyomkij, Virawudh] Univ Calif San Diego, Sch Med, Dept Psychiat, La Jolla, CA 92093 USA.
[Gustafsson, Asa B.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
[Cox, Jeffery S.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA.
[Aghi, Manish K.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA.
[An, Zhenyi] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Hetz, Claudio; Matus, Soledad] FONDAP Ctr Gerosci Brain Hlth & Metab, Santiago, Chile.
[Gestwicki, Jason E.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA.
[Sarwal, Minnie M.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA.
[Finkbeiner, Steven] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Finkbeiner, Steven] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA.
[Finkbeiner, Steven] Gladstone Inst Neurol Dis, San Francisco, CA USA.
[Debnath, Jayanta; Margeta, Marta] Univ Calif San Francisco, Sch Med, Dept Pathol, San Francisco, CA 94143 USA.
[Kajimura, Shingo] Univ Calif San Francisco, UCSF Diabet Ctr, Dept Cell & Tissue Biol, San Francisco, CA 94143 USA.
[Montell, Craig] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA.
[Kaser, Arthur] Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 2QQ, England.
[Rubinsztein, David C.] Univ Cambridge, Addenbrookes Hosp, Cambridge Inst Med Res, Dept Med Genet, Cambridge CB2 2QQ, England.
[Floto, R. Andres] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England.
[Narita, Masashi] Univ Cambridge, Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Cambridge, England.
[Miller-Fleming, Leonor] Univ Cambridge, Dept Biochem, Cambridge, England.
[Renna, Maurizio] Univ Cambridge, Dept Med Genet, Cambridge Inst Med Res, Cambridge, England.
[Randow, Felix] Univ Cambridge, Dept Med, Addenbrookes Hosp, Cambridge CB2 2QQ, England.
[Beale, Rupert] Univ Cambridge, Dept Pathol, Div Virol, Tennis Court Rd, Cambridge CB2 1QP, England.
[Amantini, Consuelo] Univ Camerino, Sch Biosci & Vet Med, I-62032 Camerino, Italy.
[Nabissi, Massimo] Univ Camerino, Sch Pharm, I-62032 Camerino, Italy.
[Santoni, Giorgio] Univ Camerino, Sch Pharm, Sect Expt Med, I-62032 Camerino, MC, Italy.
[Ferreira-Halder, Carmen Verissima] Univ Estadual Campinas, Dept Biochem & Tissue Biol, Campinas, SP, Brazil.
[Dobson, Renwick C. J.] Univ Canterbury, Biomol Interact Ctr, Sch Biol Sci, Christchurch 1, New Zealand.
[Prince, Sharon] Univ Cape Town, Dept Human Biol, ZA-7925 Cape Town, Western Provinc, South Africa.
[Davids, Lester M.] Univ Cape Town, Redox Lab, Dept Human Biol, ZA-7925 Cape Town, South Africa.
[Zervos, Antonis S.] Univ Cent Florida, Coll Med, Burnett Sch Biomed Sci, Orlando, FL 32816 USA.
[He, Yu-Ying] Univ Chicago, Dept Med, Dermatol Sect, Chicago, IL 60637 USA.
[Choi, Jayoung; Hwang, Seungmin] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA.
[Mastrianni, James A.] Univ Chicago, Pritzker Sch Med, Dept Neurol, Chicago, IL 60637 USA.
[Macleod, Kay F.] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA.
[Corbalan, Ramon; Garcia Nannig, Lorena] Univ Chile, Adv Ctr Chron Dis ACCDiS, Div Cardiovasc Dis, Fac Med, Santiago, Chile.
[Pedrozo, Zully] P Catholic Univ Chile, Adv Ctr Chron Dis ACCDiS, Fac Med, Santiago, Chile.
[Matus, Soledad] Univ Chile, Biomed Neurosci Inst, Santiago, Chile.
[Segura-Aguilar, Juan] Univ Chile, Fac Med, ICBM Mol & Clin Pharmacol, Santiago 7, Chile.
[Hetz, Claudio] Univ Chile, Fac Med, Inst Biomed Sci, Ctr Mol Studies Cell,Program Cellular,Mol Biol &, Santiago 7, Chile.
[Weaver, Timothy E.] Univ Cincinnati, Coll Med, Cincinnati Childrens Res Fdn, Cincinnati, OH USA.
[Weaver, Timothy E.] Dept Pediat, Cincinnati, OH USA.
[Czyzyk-Krzeska, Maria F.; Guan, Jun-Lin; Wang, Chenran] Dept Pediat, Coll Med, Dept Canc Biol, Cincinnati, OH USA.
[Robbins, Jeffrey] Univ Cincinnati, Cincinnati Childrens Hosp, Cincinnati, OH USA.
[Choubey, Divaker] Univ Cincinnati, Cincinnati, OH USA.
[Moreira, Paula I.] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, Coimbra, Portugal.
[Moreira, Paula I.] Fac Med, Coimbra, Portugal.
[Cruz, Maria Teresa; Liberal, Joana] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal.
[Cruz, Maria Teresa; Liberal, Joana] Fac Pharm, Coimbra, Portugal.
[Vega-Naredo, Ignacio] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, Cantanhede, Portugal.
[Batista, Maria Teresa] Univ Coimbra, Coimbra, Portugal.
[Cardoso, Sandra Morais] Univ Coimbra, Fac Med, Ctr Neurosci & Cell Biol, Coimbra, Portugal.
[Pereira, Paulo C.] Univ Coimbra, IBILI, Fac Med, Coimbra, Portugal.
[Fabri, Mario] Univ Cologne, Dept Dermatol, D-50931 Cologne, Germany.
[Hoppe, Thorsten] Univ Cologne, Inst Genet, CECAD Res Ctr, D-50931 Cologne, Germany.
[Noegel, Angelika A.] Univ Cologne, Inst Biochem 1, Fac Med, Cologne, Germany.
[Eichinger, Ludwig] Univ Cologne, Fac Med, Ctr Biochem, D-50931 Cologne, Germany.
[Edelstein, Charles L.] Univ Colorado, Boulder, CO 80309 USA.
[Weekes, Colin D.] Univ Colorado, Div Med Oncol, Dept Med, Aurora, CO USA.
[Agarwal, Rajesh; Raina, Komal] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Aurora, CO USA.
[Jani, Alkesh] Univ Colorado, Denver, CO USA.
[Jani, Alkesh] Denver VAMC, Denver, CO USA.
[Levy, Jean M. Mulcahy] Univ Colorado, Dept Pediat, Ctr Canc & Blood Disorders, Aurora, CO USA.
[Parker, Roy] Univ Colorado, HHMI, Dept Chem & Biochem, Aurora, CO USA.
[Pugazhenthi, Subbiah] Univ Colorado, Sch Med, Anschutz Med Campus, Aurora, CO USA.
[Reusch, Jane E. B.] Univ Colorado, Sch Med, Aurora, CO USA.
[Pyeon, Dohun] Univ Colorado, Sch Med, Dept Immunol & Microbiol, Aurora, CO USA.
[Bayer, K. Ulrich; Morgan, Michael J.; Thorburn, Andrew] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO USA.
[Beckham, J. David] Univ Colorado, Sch Med, Div Infect Dis, Aurora, CO USA.
[Frankel, Lisa B.; Issazadeh-Navikas, Shohreh; Lund, Anders H.] Univ Copenhagen, BRIC, Copenhagen, Denmark.
[Petersen, Morten] Univ Copenhagen, Dept Biol, Copenhagen, Denmark.
[Olsson, Stefan] Univ Copenhagen, Dept Plant & Environm Sci, Sect Genet & Microbiol, Copenhagen, Denmark.
[Tavernarakis, Nektarios] Univ Crete, Dept Basic Sci, Fac Med, Iraklion, Greece.
[Tavernarakis, Nektarios] Univ Crete, Inst Mol Biol & Biotechnol, Iraklion, Greece.
[Chamilos, Georgios; Kyrmizi, Irene] Univ Crete, Sch Med, Dept Infect Dis, Iraklion, Greece.
[Promponas, Vasilis J.] Univ Cyprus, Dept Biol Sci, Bioinformat Res Lab, CY-1678 Nicosia, Cyprus.
[Fesus, Laszlo] Univ Debrecen, Debrecen, Hungary.
[Lekli, Istvan] Univ Debrecen, Fac Pharm, Dept Pharmacol, Debrecen, Hungary.
[van Golen, Kenneth L.] Univ Delaware, Dept Biol Sci, Newark, DE USA.
[van Golen, Kenneth L.] Univ Delaware, Ctr Translat Canc Res, Newark, DE USA.
[Rocha, Sonia] Univ Dundee, Ctr Gene Regulat & Express, Coll Life Sci, Dundee DD1 4HN, Scotland.
[Ganley, Ian G.] Univ Dundee, MRC Prot Phosphorylat & Ubiquitylat Unit, Sch Life Sci, Dundee, Scotland.
[Wileman, Tom] Univ E Anglia, Norwich Med Sch, Norwich NR4 7TJ, Norfolk, England.
[Pesonen, Maija] Univ Eastern Finland, Fac Hlth Sci, Sch Pharm Toxicol, Kuopio, Finland.
[Kaarniranta, Kai] Univ Eastern Finland, Kuopio Univ Hosp, Dept Ophthalmol, Kuopio, Finland.
[Digard, Paul] Univ Edinburgh, Easter Bush, Roslin Insitute, Edinburgh EH8 9YL, Midlothian, Scotland.
[Gammoh, Noor] Univ Edinburgh, Edinburgh Canc Res Ctr, Edinburgh, Midlothian, Scotland.
[Wilkinson, Simon] Univ Edinburgh, Edinburgh Canc Res UK Ctr, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
[Distler, Joerg H. W.] Univ Erlangen Nurnberg, Dept Internal Med 3, D-91054 Erlangen, Germany.
[Moore, Michael N.] Univ Exeter, Sch Med, ECEHH, Truro, Cornwall, England.
[Talbot, Nicholas J.] Univ Exeter, Sch Biosci, Exeter, Devon, England.
[Pena, Fernando J.; Tapia, Jose A.] Univ Extremadura, Dept Med, Fac Vet Med, Caceres, Spain.
[Neri, Luca M.; Pinton, Paolo] Univ Ferrara, Dept Morphol Surg & Expt Med, I-44100 Ferrara, Italy.
[Papini, Alessio] Univ Florence, Dept Biol, Florence, Italy.
[Dunn, William A., Jr.] Univ Florida, Coll Med, Dept Anat & Cell Biol, Gainesville, FL USA.
[Notterpek, Lucia] Univ Florida, Coll Med, Dept Neurosci, Gainesville, FL USA.
[Joseph, Anna-Maria] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA.
[Wohlgemuth, Stephanie E.] Univ Florida, Dept Anim Sci, IFAS Coll Agr & Life Sci, Gainesville, FL 32611 USA.
[Adhihetty, Peter J.; Powers, Scott K.] Univ Florida, Dept Appl Physiol & Kinesiol, Gainesville, FL USA.
[Maegawa, Gustavo] Univ Florida, Dept Pediat Genet & Metab, Gainesville, FL USA.
[Behrns, Kevin E.] Univ Florida, Dept Surg, Gainesville, FL USA.
[Kim, Jae-Sung] Univ Florida, Gainesville, FL USA.
[Leeuwenburgh, Christiaan] Univ Florida, Inst Aging, Gainesville, FL USA.
[Dengjel, Joern] Univ Freiburg, Dept Dermatol, Med Ctr, Ctr Biol Syst Anal ZBSA, Hugstetter Str 55, D-79106 Freiburg, Germany.
[Yang, Zhihong] Univ Fribourg, Dept Med, Div Physiol, Fac Sci, CH-1700 Fribourg, Switzerland.
[Ming, Xiu-Fen; Xiong, Yuyan] Univ Fribourg, Dept Med, Div Physiol, CH-1700 Fribourg, Switzerland.
[Gannage, Monique] Univ Geneva, Sch Med, Dept Pathol & Immunol, CH-1211 Geneva, Switzerland.
[Gogal, Robert M., Jr.] Univ Georgia, Coll Vet Med, Dept Biosci & Diagnost Imaging, Athens, GA 30602 USA.
[Quinn, Frederick] Univ Georgia, Dept Infectious Dis, Athens, GA 30602 USA.
[Leung, Hing Y.; Ryan, Kevin M.; Tait, Stephen W. G.] Univ Glasgow, Canc Res UK Beatson Inst, Glasgow, Lanark, Scotland.
[Leung, Hing Y.; McNeish, Iain A.] Univ Glasgow, Inst Canc Sci, Glasgow, Lanark, Scotland.
[Evans, Thomas J.] Univ Glasgow, Inst Infect Immun & Inflammat, Glasgow, Lanark, Scotland.
[Helgason, Gudmundur Vignir] Univ Glasgow, Wolfson Wohl Canc Res Ctr, MVLS, Inst Canc Sci, Glasgow, Lanark, Scotland.
[Jackson, Daniel John] Univ Gottingen, Dept Geobiol, D-37073 Gottingen, Germany.
[Lingor, Paul] Univ Gottingen, Dept Neurol, D-37073 Gottingen, Germany.
[Carmona-Gutierrez, Didac; Eisenberg, Tobias; Kohlwein, Sepp D.; Madeo, Frank] Graz Univ, Inst Mol Biosci, BioTechMed Graz, Graz, Austria.
[van der Klei, Ida J.; Williams, Chris] Univ Groningen, Mol Cell Biol, Groningen, Netherlands.
[Lemberg, Marius K.] Heidelberg Univ, Ctr Mol Biol, Heidelberg, Germany.
[Parlato, Rosanna] Heidelberg Univ, Inst Anat & Cell Biol, Heidelberg, Germany.
[Lindholm, Dan] Univ Helsinki, Biomedicum, Helsinki, Finland.
[Eskelinen, Eeva-Liisa; Stratoulias, Vassilis] Univ Helsinki, Dept Biosci, Helsinki, Finland.
[Hulmi, Juha J.] Univ Helsinki, Dept Physiol, Fac Med, Helsinki, Finland.
[Wang, Yu] Univ Hong Kong, Dept Pharmacol & Pharm, Hong Kong, Hong Kong, Peoples R China.
[Su, Yu-Xiong] Univ Hong Kong, Div Oral & Maxillofacial Surg, Fac Dent, Hong Hom, Hong Kong, Peoples R China.
[Feng, Yibin] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China.
[Chang, Raymond Chuen-Chung] Univ Hong Kong, Lab Neurodegenerat Dis, Sch Biomed Sci, LKS Fac Med, Hong Kong, Hong Kong, Peoples R China.
[Eriksen, Jason L.; Zhang, Yang] Univ Houston, Coll Pharm Pharmacol & Pharmaceut Sci, Houston, TX USA.
[Frigo, Daniel E.] Univ Houston, Dept Biol & Biochem, Ctr Nucl Receptors & Cell Signaling, Houston, TX USA.
[Caplan, Allan B.] Univ Idaho, Plant Soil & Entomol Sci, Moscow, ID USA.
[Yue, Beatrice Y. J. T.] Univ Illinois, Coll Med, Dept Ophthalmol & Visual Sci, Chicago, IL USA.
[Zhou, Guofei] Univ Illinois, Coll Med, Dept Pediat, Chicago, IL USA.
[Hu, Guochang] Univ Illinois, Dept Anesthesiol, Chicago, IL USA.
[Hu, Guochang] Univ Illinois, Dept Pharmacol, Chicago, IL USA.
[Shukla, Deepak] Univ Illinois, Dept Ophthalmol, Chicago, IL 60680 USA.
[Shukla, Deepak] Univ Illinois, Dept Microbiol & Immunol, Chicago, IL 60680 USA.
[Nazarko, Volodymyr Y.; Segev, Nava] Univ Illinois, Deprtment Biochem & Mol Genet, Chicago, IL USA.
[Sun, Jun] Univ Illinois, Div Gastroenterol & Hepatol, Dept Med, Chicago, IL USA.
[Kemper, Jongsook Kim] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL USA.
[Zhang, Guo-Chang] Univ Illinois, Inst Genom Biol, Urbana, IL USA.
[Meryk, Andreas] Univ Innsbruck, Inst Biomed Aging Res, A-6020 Innsbruck, Austria.
[Romanelli, Davide; Tettamanti, Gianluca] Univ Insubria, Dept Biotechnol & Life Sci, Varese, Italy.
[Grose, Charles] Univ Iowa, Childrens Hosp, Iowa City, IA USA.
[Lira, Vitor A.] Univ Iowa, Dept Hlth & Human Physiol, Iowa City, IA USA.
[Adams, Christopher M.] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA.
[Monick, Martha M.] Univ Iowa, Dept Med, Iowa City, IA 52242 USA.
[Fingert, John H.] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA 52242 USA.
[Hulmi, Juha J.] Univ Jyvaskyla, Dept Biol Phys Act, SF-40100 Jyvaskyla, Finland.
[Marquez, Rebecca; Xu, Liang] Univ Kansas, Lawrence, KS 66045 USA.
[Marquez, Rebecca; Xu, Liang] Univ Kansas, Ctr Canc, Dept Mol Biosci, Lawrence, KS 66045 USA.
[Marquez, Rebecca; Xu, Liang] Univ Kansas, Ctr Canc, Dept Radiat Oncol, Lawrence, KS 66045 USA.
[Chen, Qi; Ding, Wen-Xing] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66103 USA.
[Hsu, Chin] Univ Kaohsiung, Med Univ, Dept Physiol, Fac Med,Coll Med, Kaohsiung, Taiwan.
[Chen, Gang; Luo, Jia] Univ Kentucky, Coll Med, Dept Pharmacol & Nutrit Sci, Lexington, KY USA.
[Rucker, Edmund B., III] Univ Kentucky, Dept Biol, Lexington, KY USA.
[Dickson, Robert C.] Univ Kentucky, Dept Mol & Cellular Biochem, Lexington, KY USA.
[Craven, Rolf J.] Univ Kentucky, Dept Pharmacol & Nutrit Sci, Lexington, KY USA.
[St Clair, Daret] Univ Kentucky, Dept Toxicol & Canc Biol, Lexington, KY USA.
[Frey, Norbert; Kuhn, Christian] Univ Kiel, Dept Cardiol, Kiel, Germany.
[Rosenstiel, Philip] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany.
[Huebbe, Patricia; Pallauf, Kathrin; Rimbach, Gerald] Univ Kiel, Inst Human Nutr & Food Sci, Kiel, Germany.
[Denizot, Melanie] Univ La Reunion, CYROI, IRG Immunopathol & Infect Res Grouping, Reunion, Reunion.
[Gravina, Giovanni Luca] Univ Aquila, Dept Biotechnol & Appl Clin Sci, Div Radiotherapy & Radiobiol, I-67100 Laquila, Italy.
[Mayer, Andreas] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland.
[Clarke, Peter G. H.; Ginet, Vanessa; Puyal, Julien] Univ Lausanne, Dept Fundamental Neurosci, Fac Biol & Med, Lausanne, Switzerland.
[Cottet, Sandra; Schorderet, Daniel F.] Univ Lausanne, Dept Ophthalmol, Lausanne, Switzerland.
[Noureini, Sakineh Kazemi] Hakim Sabzevari Univ, Dept Biol, Fac Basic Sci, Sabzevar, Iran.
[Andreadi, Catherine K.; Brown, Karen] Univ Leicester, Dept Canc Studies, Leicester, Leics, England.
[Giorgini, Flaviano] Univ Leicester, Dept Genet, Leicester, Leics, England.
[Garg, Abhishek D.] Univ Leuven, Campus Gasthuisberg, Dept Cellular & Mol Med, Lab Cell Death Res & Therapy, Leuven, Belgium.
[Vandenberghe, Wim] Univ Leuven, Dept Neurosci, Leuven, Belgium.
[Claerhout, Sofie] KU Leuven Univ Leuven, Ctr Human Genet, Leuven, Belgium.
[Claerhout, Sofie] VIB Ctr Biol Dis, Leuven, Belgium.
[Mottet, Denis] Univ Liege, GIGA Signal Transduct Dept, Prot Signalisat & Interact Lab, Liege, Belgium.
[Staels, Bart] Univ Lille, INSERM UMR1011, Inst Pasteur Lille, Lille, France.
[Terro, Faraj] Univ Limoges, Dept Histol & Cell Biol, Limoges, France.
[Clague, Michael J.] Univ Liverpool, Cellular & Mol Physiol, Inst Translat Med, Liverpool L69 3BX, Merseyside, England.
[Erman, Andreja] Univ Ljubljana, Inst Cell Biol, Fac Med, Ljubljana, Slovenia.
[Campanella, Michelangelo] Univ London, RVC Dept Comparat Biomed Sci, UCL Consortium Mitochondrial Res, London, England.
[Sylvester, Paul W.] Univ Louisiana Monroe, Sch Pharm, Monroe, LA USA.
[Cheng, Alan] Univ Louisville, Dept Biochem & Mol Genet, Louisville, KY 40292 USA.
[Chesney, Jason; Telang, Sucheta] Univ Louisville, Dept Med Hem Onc, Louisville, KY 40292 USA.
[Hill, Bradford G.] Univ Louisville, Dept Med, Inst Mol Cardiol, Diabet & Obes Ctr, Louisville, KY 40292 USA.
[Sen, Utpal] Univ Louisville, Dept Physiol, Louisville, KY 40292 USA.
[Li, Chi] Univ Louisville, James Graham Brown Canc Ctr, Dept Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA.
[Kumar, Ashok] Univ Louisville, Sch Med, Dept Anat Sci & Neurobiol, Louisville, KY 40292 USA.
[Tyagi, Suresh C.] Univ Louisville, Sch Med, Dept Physiol & Biophys, Louisville, KY 40292 USA.
[Kruger, Rejko] Univ Luxembourg, Luxembourg Ctr Syst Biomed, Luxembourg, Luxembourg.
[Lu, Jiahong] Univ Macau, State Key Lab Qual Res Chinese Med, Inst Chinese Med Sci, Macau, Peoples R China.
[Balzan, Rena] Univ Malta, Dept Physiol & Biochem, Fac Med & Surg, Msida, Malta.
[Lisanti, Michael P.] Univ Manchester, Breakthrough Breast Canc Res Unit, Manchester Ctr Cellular Metab, Manchester M13 9PL, Lancs, England.
[Tournier, Cathy] Univ Manchester, Fac Life Sci, Manchester, Lancs, England.
[Sotgia, Federica] Univ Manchester, Inst Canc Sci, Fac Med & Human Sci, Manchester, Lancs, England.
[Gibson, Spencer B.] Univ Manitoba, CancerCare Manitoba, Manitoba Inst Cell Biol, Dept Biochem, Winnipeg, MB, Canada.
[Gibson, Spencer B.] Univ Manitoba, Dept Med Genet & Immunol, Winnipeg, MB, Canada.
[Ghavami, Saeid] Univ Manitoba, Dept Human Anat & Cell Sci, Winnipeg, MB, Canada.
[Halayko, Andrew J.] Univ Manitoba, Dept Physiol & Pathophysiol, Winnipeg, MB, Canada.
[Kirshenbaum, Lorrie A.] Univ Manitoba, Inst Cardiovasc Sci, Coll Med, Fac Hlth Sci, Winnipeg, MB, Canada.
[Sharma, Shweta] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA.
[Zhang, Yanjin] Univ Maryland, Dept Vet Med, College Pk, MD 20742 USA.
[Fang, Shengyun] Univ Maryland, Sch Med, Sch Med, Ctr Biomed Engn & Technol,Dept Physiol, Baltimore, MD 21201 USA.
[Wu, Junfang] Univ Maryland, Sch Med, Dept Anesthesiol & Ctr Shock, Trauma & Anesthesiol Res STAR,Natl Study Ctr Trau, Baltimore, MD 21201 USA.
[Lipinski, Marta M.] Univ Maryland, Sch Med, Dept Anesthesiol, Baltimore, MD 21201 USA.
[Njar, Vincent C. O.] Univ Maryland, Sch Med, Dept Chem, Baltimore, MD 21201 USA.
[Jackson, William T.; Kalvakolanu, Dhan V.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
[Yang, Peixin] Univ Maryland, Sch Med, Dept Obstet Gynecol & Reprod Sci, Baltimore, MD 21201 USA.
[Aurelian, Laure] Univ Maryland, Sch Med, Dept Pharmacol, Baltimore, MD 21201 USA.
[Cheng, Hua] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Baehrecke, Eric H.; Velentzas, Panagiotis D.] Univ Massachusetts, Sch Med, Dept Mol Cell & Canc Biol, Worcester, MA 01605 USA.
[Gao, Fen-Biao] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01605 USA.
[Davis, Roger J.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA.
[Maiese, Kenneth] Univ Med & Dent New Jersey, Cellular & Mol Signaling, Newark, NJ 07103 USA.
[Lindqvist, Lisa M.] Cell Signalling & Cell Death Div, Parkville, Vic, Australia.
[Lindqvist, Lisa M.] Univ Melbourne, Walter & Eliza Hall Inst Med Res, Dept Med Biol, Parkville, Vic 3052, Australia.
[White, Anthony R.] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia.
[Delbridge, Lea M. D.] Univ Melbourne, Dept Physiol, Parkville, Vic 3052, Australia.
[Pepe, Salvatore] Univ Melbourne, Murdoch Childrens Res Inst, Dept Paediat, Royal Childrens Hosp, Melbourne, Vic, Australia.
[Kim, Michael D.] Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA.
[Man, Na] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
[Soleimanpour, Scott A.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Lieberman, Andrew P.; Lukacs, Nicholas W.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA.
[Towns, Roberto] Univ Michigan, Ann Arbor, MI 48109 USA.
[Duncan, Mara C.] Univ Michigan, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA.
[Swanson, Michele S.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
[Lee, Jun Hee] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
[Klionsky, Daniel J.; Feng, Yuchen; Gatica, Damian; Jin, Meiyan; Kumar, Anuj; Liu, Xu; Orban, Daniel P.; Parzych, Katherine R.; Wen, Xin; Xu, Haoxing; Xu, Ziheng; Yao, Zhiyuan] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA.
[Zacks, David N.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
[Xie, Chuan-Ming] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA.
[Sun, Yi; Zhao, Yongchao] Univ Michigan, Dept Radiat Oncol, Div Radiat & Canc Biol, Ann Arbor, MI 48109 USA.
[Klionsky, Daniel J.; Ariosa, Aileen R.; Bernard, Amelie; Delorme-Axford, Elizabeth; Feng, Yuchen; Gatica, Damian; Jin, Meiyan; Liu, Xu; Orban, Daniel P.; Parzych, Katherine R.; Popelka, Hana; Wen, Xin; Xu, Ziheng; Yao, Zhiyuan] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA.
[Burmeister, Margit] Univ Michigan, Mol & Behav Neurosci Inst, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
[Burmeister, Margit] Univ Michigan, Mol & Behav Neurosci Inst, Dept Psychiat, Ann Arbor, MI 48109 USA.
[Burmeister, Margit] Univ Michigan, Mol & Behav Neurosci Inst, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Hua, Ya] Univ Michigan, Neurosurg, Ann Arbor, MI 48109 USA.
[Kahana, Alon] Univ Michigan, Ophthalmol & Visual Sci, Kellogg Eye Ctr, Ann Arbor, MI 48109 USA.
[Liu, Fei] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA.
[Minucci, Saverio] Univ Milan, Dept Expt Oncol, European Inst Oncol, Milan, Italy.
[Minucci, Saverio] Dept Biosci, Milan, Italy.
[Avagliano, Laura; Marconi, Anna Maria] Univ Milan, Dept Hlth Sci, Milan, Italy.
[Vitale, Giovanni] Univ Milan, Ist Auxol Italiano, Dept Clin Sci & Community Hlth, Milan, Italy.
[Ludovico, Paula] Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Hlth Sci, Braga, Portugal.
[Sousa, Maria Joao] Univ Minho, Mol & Environm Biol Ctr CBMA, Dept Biol, Braga, Portugal.
[Ludovico, Paula] ICVS 3Bs PT Govt Associate Lab, Braga, Portugal.
[Kim, Do-Hyung] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN USA.
[Mauvezin, Caroline] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA.
[Abedin, Md Joynal] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Karim, Md Razaul] Univ Minnesota, Dept Neurosci, Minneapolis, MN 55455 USA.
[Saluja, Ashok K.] Univ Minnesota, Dept Surg, Box 242 UMHC, Minneapolis, MN 55455 USA.
[Imbriano, Carol; Pinti, Marcello] Univ Modena & Reggio Emilia, Dept Life Sci, Modena, Italy.
[Gibellini, Lara] Univ Modena & Reggio Emilia, Dept Surg Med Dent & Morphol Sci, Modena, Italy.
[Cossarizza, Andrea] Univ Modena & Reggio Emilia, Sch Med, Dept Surg Med Dent & Morphol Sci, Modena, Italy.
[Koechlin-Ramonatxo, Christelle] Univ Montpellier, INRA, UMR 866, Dynam Musculaire & Metab, F-34059 Montpellier, France.
[Candau, Robin] Univ Montpellier, UMR 866, Dynam Musculaire & Metab, F-34059 Montpellier, France.
[Godefroy, Nelly; Martinand-Mari, Camille] Univ Montpellier, UMR 5554, F-34059 Montpellier, France.
[Valdor, Rut] Univ Murcia, IMIB Virgen Arrixaca Hosp, Human Anat & Psycobiol Dept, Cell Therapy & Hematopoiet Transplantat Unit, Murcia, Spain.
[Shidoji, Yoshihiro] Nagasaki Univ, Mol & Cellular Biol, Grad Sch Human Hlth Sci, Nagasaki 852, Japan.
[Arnould, Thierry; Michiels, Carine] Univ Namur, Lab Biochem & Cell Biol URBC, Namur Res Inst Life Sci NARILIS, Namur, Belgium.
[Hamer, Isabelle] Univ Namur, Res Unit Mol Physiol URPhyM, Namur, Belgium.
[Ciarcia, Roberto; De Martino, Luisa; Fiorito, Filomena; Florio, Salvatore; Montagnaro, Serena; Pagnini, Ugo] Univ Naples Federico II, Dept Vet Med & Anim Prod, Naples, Italy.
[Donohue, Terrence M., Jr.; Thomes, Paul G.] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE USA.
[Buch, Shilpa] Univ Nebraska Med Ctr, Omaha, NE USA.
[Franco, Rodrigo] Univ Nebraska, Redox Biol Ctr, Lincoln, NE USA.
[Franco, Rodrigo] Sch Vet Med & Biomed Sci, Lincoln, NE USA.
[Ozbun, Michelle A.] Univ New Mexico, Ctr Comprehens Canc, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA.
[Dokladny, Karol; Moseley, Pope L.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA.
[Cleyrat, Cedric] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA.
[Cleyrat, Cedric] Canc Res & Treatment Ctr, Albuquerque, NM USA.
[Deretic, Vojo; Kimura, Tomonori; Mandell, Michael A.] Univ New Mexico, Hlth Sci Ctr, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA.
[Cheluvappa, Rajkumar] Univ New S Wales, Inflammat & Infect Res Ctr, Sch Med Sci, Sydney, NSW, Australia.
[Kaakoush, Nadeem O.] Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW, Australia.
[Zhang, Xu Dong] Univ Newcastle, Sch Biomed Sci & Pharm, Newcastle, NSW 2300, Australia.
[Jin, Lei] Univ Newcastle, Sch Med & Publ Hlth, Callaghan, NSW 2308, Australia.
[Auberger, Patrick] Univ Nice, INSERM U1065, C3M, Nice, France.
[Hofman, Paul] Univ Nice Sophia Antipolis, INSERM U1081, CNRS 7284, Fac Med, F-06189 Nice, France.
[Bulavin, Dmitry V.] Univ Nice Sophia Antipolis, IRCAN, F-06189 Nice, France.
[Vouret-Craviari, Valerie] Univ Nice Sophia Antipolis, IRCAN, F-06189 Nice, France.
[Aoki, Hiroshi] Niigata Univ, Dept Neurosurg, Brain Res Inst, Niigata, Japan.
[Bultman, Scott J.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Ting, Jenny Pan-yun] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA.
[Der, Channing J.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Ting, Jenny Pan-yun] Univ N Carolina, Lineberger Comprehens Canc Ctr, Inst Inflammatory Dis, Ctr Translat Immunol, Chapel Hill, NC 27599 USA.
[Kawula, Thomas] Univ N Carolina, Microbiol & Immunol, Chapel Hill, NC USA.
[Wu, Min] Univ N Dakota, Dept Biomed Sci, Sch Med & Hlth Sci, Grand Forks, ND 58201 USA.
[Basu, Alakananda] Univ N Texas, Hlth Sci Ctr, Dept Mol & Med Genet, Ft Worth, TX USA.
[Layfield, Robert] Univ Nottingham, Sch Life Sci, Nottingham NG7 2RD, England.
[Adachi, Hiroaki] Univ Occupat & Environm Hlth, Sch Med, Dept Neurol, Fukuoka, Japan.
[Harada, Masaru] Univ Occupat & Environm Hlth, Dept Internal Med 3, Kitakyushu, Fukuoka, Japan.
[Xu, Jian] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA.
[Ramesh, Rajagopal; Zhao, Zhizhuang J.] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.
[Xie, Zhonglin] Univ Oklahoma, Hlth Sci Ctr, Sect Mol Med, Dept Med, Oklahoma City, OK USA.
[Jain, Ashish; Rusten, Tor Erik] Univ Oslo, Ctr Canc Biomed, Oslo, Norway.
[Seglen, Per O.] Univ Oslo, Ctr Mol Med Norway NCMM, Oslo, Norway.
[Torgersen, Maria Lyngaas] Univ Oslo, Dept Biochem, Inst Canc Res, Oslo, Norway.
[Mills, Ian G.] Univ Oslo, Dept Mol Oncol, Dept Urol, Oslo, Norway.
[Nilsen, Hilde] Univ Oslo, Dept Clin Mol Biol, Oslo, Norway.
[Petrovski, Goran] Univ Oslo, Dept Ophthalmol, Oslo, Norway.
[Mills, Ian G.] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Lisburn Rd, Belfast, Antrim, North Ireland.
[Blomhoff, Heidi Kiil; Simonsen, Anne] Univ Oslo, Inst Basic Med Sci, Oslo, Norway.
[Engedal, Nikolai; Gerner, Lisa] Univ Oslo, Oslo Univ Hosp, Ctr Mol Med Norway, Nord EMBL Partnership, Oslo, Norway.
[Hensel, Michael] Univ Osnabrueck, Div Microbiol, Osnabruck, Germany.
[Ungermann, Christian] Univ Osnabrueck, Fachbereich Biol Chem, Osnabruck, Germany.
[Slack, Ruth] Univ Ottawa, Dept Cellular & Mol Med, Fac Med, Ottawa, ON, Canada.
[Gibbings, Derrick J.] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON, Canada.
[Marino, Guillermo] Univ Oviedo, Dept Anim Physiol, Fac Med, Campus Cristo, Oviedo, Spain.
[Buchan, Alastair M.] Univ Oxford, Acute Stroke Programme, Radcliffe Dept Med, Oxford, England.
[Hammond, Ester M.] Univ Oxford, CRUK MRC Oxford Inst Radiat Oncol, Oxford, England.
[Poulton, Joanna] Univ Oxford, Nuffield Dept Obstet & Gynaecol, Oxford, England.
[Brini, Marisa; Valle, Luisa Dalla; Scovassi, A. Ivana] Univ Padua, Dept Biol, Padua, Italy.
[Bonaldo, Paolo; Chen, Peiwen; Grumati, Paolo] Univ Padua, Dept Mol Med, Padua, Italy.
[Viola, Giampietro] Univ Padua, Dept Womans & Childs Hlth, Lab Oncohematol, Padua, Italy.
[Monick, Martha M.; Sandri, Marco; Zaglia, Tania] Univ Padua, Venetian Inst Mol Med, Dept Biomed Sci, Padua, Italy.
[Agnello, Maria; Chiarelli, Roberto; Luparello, Claudio; Roccheri, Maria Carmela] Univ Palermo, Dipartimento Sci &Tecnol Biol, Chim & Farmaceutiche STEBICEF, Palermo, Italy.
[Bettuzzi, Saverio; Rizzi, Federica] Univ Parma, Dept Biomed Biotechnol & Translat Sci, I-43100 Parma, Italy.
[Comincini, Sergio; Palumbo, Silvia] Univ Pavia, Dept Biol & Biotechnol, Via Palestro 3, I-27100 Pavia, Italy.
[Emanuele, Enzo] Univ Pavia, Dept Hlth Sci, Via Palestro 3, I-27100 Pavia, Italy.
[Koumenis, Constantinos] Univ Penn, Perelman Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA.
[O'Dwyer, Peter J.; Vogl, Dan T.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Gonzalez-Alegre, Pedro] Univ Penn, Ctr Cell & Mol Therapy, Children Hosp Philadelphia, Dept Neurol,Perelman Sch Med, Philadelphia, PA 19104 USA.
[Mitchell, Claire H.] Univ Penn, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA.
[Boesze-Battaglia, Kathleen] Univ Penn, Dept Biochem, SDM, Philadelphia, PA 19104 USA.
[Cherry, Sara] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA.
[Zhang, Lin] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA.
[Zhang, Lin] Perelman Sch Med, Philadelphia, PA USA.
[Sanchez, Anthony M. J.] Univ Perpignan Via Domitia, Lab Europee Performance St Altitude, EA 4604, Ft Romeu, France.
[Romani, Luigina] Univ Perugia, Dept Expt Med, I-06100 Perugia, Italy.
[De Tata, Vincenzo; Fornai, Francesco; Lenzi, Paola] Univ Pisa, Dept Translat Res & New Technol Med & Surg, Pisa, Italy.
[Cavallini, Gabriella] Univ Pisa, Interdepartmental Res Ctr Biol & Pathol Aging, Pisa, Italy.
[Singh, Shivendra V.] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr Res Pavil, Pittsburgh, PA USA.
[Johnson, Daniel E.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Tsung, Allan] Univ Pittsburgh, Med Ctr, Dept Surg, Pittsburgh, PA USA.
[Gomez, Hernando] Univ Pittsburgh, Dept Crit Care Med, Ctr Crit Care Nephrol, Clin Res Invest & Syst Modeling Acute Illness, Pittsburgh, PA USA.
[Coyne, Carolyn B.] Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA USA.
[Rabinowich, Hannah] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA.
[Kang, Rui; Tang, Daolin] Univ Pittsburgh, Dept Surg, Hillman Canc Ctr, Pittsburgh, PA USA.
[Fan, Jie; Lee, Yong J.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA.
[Lotze, Michael T.] Univ Pittsburgh, Dept Surg, Inst Canc, Pittsburgh, PA USA.
[Perlmutter, David H.] Univ Pittsburgh, Pittsburgh, PA USA.
[Ouyang, Hongjiao] Univ Pittsburgh, Sch Dent Med, Dept Endodont, Pittsburgh, PA USA.
[Kaynar, A. Murat] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA USA.
[Kaynar, A. Murat] Univ Pittsburgh, Sch Med, Dept Crit Care Med, Pittsburgh, PA USA.
[Lu, Binfeng] Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA USA.
[Chu, Charleen T.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA.
[Chu, Charleen T.] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15260 USA.
[Pak, Stephen C.; Silverman, Gary A.] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15260 USA.
[Zhang, Lin] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15260 USA.
[Stang, Michael T.] Univ Pittsburgh, Sch Med, Dept Surg, Div Endocrine Surg, Pittsburgh, PA 15260 USA.
[Isenberg, Jeffrey S.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15260 USA.
[Page, Guylene] Univ Poitiers, Mol Targets & Therapeut Alzheimers Dis EA3808, Poitiers, France.
[Lima, Raquel T.; Seca, Hugo; Vasconcelos, M. Helena; Xavier, Cristina P. R.] Univ Porto, Canc Drug Resistance Grp, IPA TIMUP, Inst Mol Pathol & Immunol, Rua Campo Alegre 823, P-4100 Oporto, Portugal.
[Seca, Hugo; Vasconcelos, M. Helena] Univ Porto, Dept Biol Sci, Fac Pharm, Rua Campo Alegre 823, P-4100 Oporto, Portugal.
[Lima, Raquel T.] Univ Porto, Dept Pathol & Oncol, Fac Pharm, Rua Campo Alegre 823, P-4100 Oporto, Portugal.
[Lima, Raquel T.; Seca, Hugo; Vasconcelos, M. Helena; Xavier, Cristina P. R.] Univ Porto, i3S, Rua Campo Alegre 823, P-4100 Oporto, Portugal.
[Joubert, Annie M.; Nolte, Elsie Magdalena; Theron, Anne E.] Univ Pretoria, Dept Physiol, ZA-0002 Pretoria, Gauteng, South Africa.
[Asselin, Eric] Univ Quebec Trois Rivieres, Dept Biol & Med, Trois Rivieres, PQ GA9 5H7, Canada.
[Walker, Mark J.] Univ Queensland, Australian Infect Dis Res Ctr, Brisbane, Qld, Australia.
[Walker, Mark J.] Sch Chem & Mol Biosci, Brisbane, Qld, Australia.
[Wolvetang, Ernst J.] Univ Queensland, AIBN, Brisbane, Qld, Australia.
[Manzoni, Claudia] Univ Reading, Sch Pharm, Reading, Berks, England.
[Lewis, Patrick A.] Univ Reading, Sch Pharm, Whiteknights, Reading, Berks, England.
[Brookes, Paul S.; Johnson, Gail V. W.] Univ Rochester, Med Ctr, Dept Anesthesiol, Rochester, NY 14642 USA.
[Sparks, Janet D.] Univ Rochester, Med Ctr, Dept Pathol & Lab Med, Rochester, NY 14642 USA.
[Giordano, Antonio] Univ Siena, Dept Med Surg & Neurosci, Via Laterina 8, I-53100 Siena, Italy.
[Sciarretta, Sebastiano] Univ Roma La Sapienza, Dept Med Surg Sci & Biotechnol, Latina, Italy.
[Aquilano, Katia; Campello, Silvia; Ciriolo, Maria Rosa; Di Bartolomeo, Sabrina; Filomeni, Giuseppe; Barbato, Daniele Lettieri; Piacentini, Mauro] Univ Roma Tor Vergata, Dept Biol, Rome, Italy.
[Schiavi, Alfonso] Univ Roma Tor Vergata, Dept Biomed & Prevent, Rome, Italy.
[Franco, Rodrigo] Univ Roma Tor Vergata, Dept Chem, Rome, Italy.
[Ozbun, Michelle A.] Univ Roma Tor Vergata, Dept Clin Sci & Translat Med, Rome, Italy.
[Bernassola, Francesca] Univ Roma Tor Vergata, Dept Expt Med & Surg, Rome, Italy.
[Melino, Gerry] Univ Roma Tor Vergata, Dept Surg & Expt Med, Rome, Italy.
[Di Daniele, Nicola; Federici, Massimo; Menghini, Rossella] Univ Roma Tor Vergata, Dept Syst Med, Rome, Italy.
[Cecconi, Francesco; Corazzari, Marco] Univ Roma Tor Vergata, Dept Biol, Rome, Italy.
[Sibirny, Andriy A.] Univ Rzeszow, Inst Biol, Rzeszow, Poland.
[Dini, Luciana] Univ Salento, Dept Biol & Environm Sci & Technol, Lecce, Italy.
[Fimia, Gian Maria] Univ Salento, Dept Biol & Environm Sci & Technol DiSTeBA, Lecce, Italy.
[Iovane, Valentina] Univ Salento, Dept Pharm, Salerno, Italy.
[Valente, Enza Maria] Univ Salento, Sect Neurosci, Dept Med & Surg, Salerno, Italy.
[Machado-Santelli, Glaucia M.] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Sao Paulo, SP, Brazil.
[Goncalves, Dawit A. P.; Kettelhut, Isis do Carmo; Machado, Juliano] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Ribeirao Preto, SP, Brazil.
[Navegantes, Luiz C.; Silveira, Wilian A.] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Physiol, Ribeirao Preto, SP, Brazil.
[Brum, Patricia Chakur; Jannig, Paulo Roberto] Univ Sao Paulo, Sch Phys Educ & Sport, Cellular & Mol Exercise Physiol Lab, Sao Paulo, Brazil.
[Man, Na; Wen, Longping; Zhang, Yunjiao] Univ Sci & Technol China, Hefei, Anhui, Peoples R China.
[Mei, Yide] Univ Sci & Technol China, CAS Key Lab Innate Immun & Chron Dis, Sch Lifesci, Hefei, Anhui, Peoples R China.
[Shi, Qinghua] Univ Sci & Technol China, Sch Life Sci, Hefei, Anhui, Peoples R China.
[Shi, Qinghua] Hefei Natl Lab Phys Sci Microscale, Hefei, Anhui, Peoples R China.
[Wu, Mian] Univ Sci & Technol China, Sch Life Sci, Hefei, Anhui, Peoples R China.
[Daza, Paula] Univ Seville, Dept Cell Biol, Seville, Spain.
[Cordero, Mario D.] Univ Seville, Inst Biomed Sevilla IBIS, Dept Oral Med, Seville, Spain.
[King, Jason S.] Univ Sheffield, Dept Biomed Sci, Sheffield S10 2TN, S Yorkshire, England.
[Boucher, Marie-Josee] Univ Sherbrooke, Fac Med & Sci St, Dept Med, Div Gastroenterol, Sherbrooke, PQ J1K 2R1, Canada.
[Del Bello, Barbara; Maellaro, Emilia] Univ Siena, Dept Mol & Dev Med, Via Laterina 8, I-53100 Siena, Italy.
[Poprawa, Izabela; Rost-Roszkowska, Magdalena] Univ Silesia, Dept Anim Histol & Embryol, Katowice, Poland.
[Tan, Ming] Univ S Alabama, Mitchell Canc Inst, Mobile, AL 36688 USA.
[Kumar, Sharad] Univ S Australia, Adelaide, SA 5001, Australia.
[Kumar, Sharad] Ctr Canc Biol, SA Pathol, Adelaide, SA, Australia.
[Morrison, Janna L.] Univ S Australia, Early Origins Adult Hlth Res Grp, Sch Pharm & Med Sci, Sansom Inst Hlth Res, Adelaide, SA 5001, Australia.
[Cui, Taixing; Fan, Daping] Univ S Carolina, Sch Med, Dept Cell Biol & Anat, Columbia, SC 29208 USA.
[Ray, Swapan K.] Univ S Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC 29208 USA.
[Baumgarner, Bradley L.] Univers South Carolina Upstate, Dept Biol, Div Nat Sci & Engn, Spartanburg, SC USA.
[Chatterjee, Saurabh] Univ S Carolina, Environm Hlth & Dis Lab, Dept Environm Hlth Sci, Columbia, SC 29208 USA.
[Pattison, Scott] Univ S Dakota, Div Basic Biomed Sci, Vermillion, SD 57069 USA.
[Wang, Hongmin] Univ S Dakota, Sanford Sch Med, Div Basic Biomed Sci, Vermillion, SD 57069 USA.
[Wang, Xuejun] Univ S Dakota, Vermillion, SD 57069 USA.
[Dickey, Chad A.] Univ S Florida, Byrd Alzheimers Inst, Tampa, FL USA.
[Nanjundan, Meera] Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL USA.
[Uversky, Vladimir N.] Univ S Florida, Dept Mol Med, Tampa, FL USA.
[Zhou, Shu-Feng] Univ S Florida, Dept Pharmaceut Sci, Tampa, FL USA.
[Jinwal, Umesh Kumar] Univ S Florida, Dept Pharmaceut Sci, Coll Pharm, Byrd Alzheimers Inst, Tampa, FL USA.
[Cragg, Mark S.] Univ Southampton, Canc Sci, Southampton, Hants, England.
[Tumbarello, David A.] Univ Southampton, Ctr Biol Sci, Highfield Campus, Southampton, Hants, England.
[Jung, Jae U.; Liang, Chengyu; Ou, Jing-hsiung James; Schoenthal, Axel H.] Univ S Carolina, Dept Mol Microbiol & Immunol, Keck Sch Med, Los Angeles, CA USA.
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EM klionsky@umich.edu
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Lazo, Pedro /M-6435-2014; antonioli, manuela/F-5898-2015; Yu, Jun
/D-8569-2015; Cenci, Simone/J-7700-2016; Milan, Enrico/J-8343-2016;
Pacelli, Consiglia/J-9032-2016; Moreira, Paula/B-3608-2009;
Gomez-Sanchez, Ruben/I-4908-2014; Zhang, Li/K-2447-2016; Seki,
Ekihiro/K-2481-2016; Rimbach, Gerald/A-7178-2011; Buchan,
Alastair/B-9095-2009; Frey, Norbert/A-9695-2010; Liu, Yule/E-5700-2010;
Viola, Giampietro/I-4095-2012; Knecht, Erwin/K-2432-2014; Corti,
Olga/I-4981-2016; Troncoso, Rodrigo/I-1915-2013; Lemaire,
Stephane/A-3530-2008; Schwarten, Melanie/G-6407-2013; Corasaniti, Maria
Tiziana/N-1332-2015; Westermann, Benedikt/H-7766-2013; Nakatogawa,
Hitoshi/D-5155-2015; Digard, Paul/B-7717-2008; Lanzi,
Cinzia/J-6539-2016; Song, Jie/J-6684-2016; Dupuis, Luc/A-6981-2012;
Vachova, Libuse/H-7620-2014; Oshima, Shigeru/C-9865-2015; Lezoualc'h,
Frank/E-5031-2016; Rouis, Mustapha/E-4993-2016; Mami-Chouaib,
Fathia/E-5267-2016; Mauvezin, Caroline/B-5803-2016; An,
Zhenyi/H-9061-2016; Gotor, Cecilia/B-7173-2012; PTMS, RNEM/C-1589-2014;
Chouaib, Salem/F-7939-2016; Poulton, Joanna/I-3913-2016; Schroder,
Bernd/C-5504-2011; Jungbluth, Heinz/B-8893-2012; Le Cam,
Laurent/O-1408-2016; Hussain, Salik/O-1687-2016; Fiorito,
Filomena/O-2175-2016; Giordano, Antonio/F-1927-2010; Machado-Santelli,
Glaucia /C-6775-2013; Cervia, Davide/A-8782-2010; Wang,
Yitao/O-5184-2016; Li, Rui/O-7397-2016; Reichert, Andreas/A-4090-2012;
Soenen, Stefaan/D-7370-2014; Tapia, Jose/C-5181-2008; Wang,
Haichao/K-6310-2012; Gorski, Sharon/E-9375-2012; Munoz-Pinedo,
Cristina/B-6118-2008; Vasconcelos, M. Helena/J-9547-2013; Molinari,
Marco/A-9624-2010; Vitale, Giovanni/B-6548-2008; Piacentini,
Mauro/I-2411-2016; ferraro, elisabetta/K-3904-2016; Nardacci,
Roberta/K-6555-2016; Ciriolo, Maria /K-6572-2016; Chiacchiera,
Fulvio/K-6740-2016; Sanchez-Prieto, Ricardo/B-6877-2008; Facchiano,
Antonio/K-5984-2016; AQUILANO, KATIA/K-8888-2016; Ubukata,
Makoto/B-8856-2012; Xu, Chuanshan/A-4527-2015; Poletti,
Angelo/A-9016-2011; Liu, Zexian/D-1153-2011; Szegezdi, Eva/B-7142-2008;
Rodrigues, Cecilia/M-3572-2013; Palkova, Zdena /M-8692-2014; LEE, Sung
Sik/C-6438-2013; Villar-Rayo, Marga/J-4155-2012; Mizushima,
Noboru/C-3635-2009; Segui-Simarro, Jose M./J-5959-2014; Segura-Aguilar,
Juan/H-8839-2013; Wang, Chengshu/A-1656-2011; Viscomi, Maria
Teresa/G-4173-2011; Filippi-Chiela, Eduardo/F-1959-2014; Malorni,
Walter/G-5874-2016; Yang, Peixin/G-9036-2016; Knavelsrud,
Helene/G-9302-2016; trisciuoglio, Daniela/H-2131-2016; Chan, Matthew
/J-2884-2013; De Santi, Mauro/F-5401-2013; Wu, William K.K./A-3277-2009;
GROS, Frederic/G-6332-2013; Arimoto, Hirokazu/E-9414-2010; Jannig,
Paulo/E-9482-2013; Di Renzo, Livia/D-1143-2013; Clarke,
Robert/A-6485-2008; Morrison, Janna/B-8308-2009; Navegantes, Luiz
Carlos/E-5283-2012; Poirot, Marc/K-3551-2012; Van Kaer, Luc/H-1033-2015;
De Meyer, Guido/R-8129-2016; Penninger, Josef/I-6860-2013; Galluzzi,
Luca/G-3969-2012; Goncalves, Dawit/S-3648-2016; Nanotechnology
Characterization Lab, NCL/K-8454-2012; Sachse, Carsten/H-2727-2012;
Koike, Masato/F-9584-2010; Perez-Sala, Dolores/L-5969-2014; Franco,
Rodrigo/D-9470-2013; Lipinski, Marek/S-9371-2016; Chuang,
Tsung-Hsien/F-9679-2010; brest, patrick/B-7311-2012; Revuelta,
Jose/C-2324-2012; Berchem, Guy/C-9364-2014; Kriston-Vizi,
Janos/L-6021-2013; Kanki, Tomotake/H-7250-2012; Jimenez,
Alberto/A-6234-2009; Martin-Acebes, Miguel/L-2258-2014;
Esteban-Martinez, Lorena/B-1854-2017; Ramonatxo, Christelle/B-2929-2017;
Guillen, Carlos/J-9728-2014; Zhang, David/O-9396-2016; Awale,
Suresh/B-6354-2017; Suzuki, Hidekazu/J-4396-2013; Braus,
Gerhard/G-3999-2012; Folini, Marco/B-9607-2017; Fan,
Chunhai/A-7569-2011; Juhasz, Gabor/G-5622-2013; Knecht,
Erwin/A-9366-2014; iMed.ULisboa, CellFun /A-4244-2014; Wang, Yu
Tian/J-8255-2015; Minina, Elena/C-9888-2017; Dubey, Vikash/B-3542-2008;
Wolvetang, Ernst/D-6644-2017; Poirot, Sandrine/D-5448-2017; Garg,
Abhishek/D-5230-2012; Hill, Bradford/I-4154-2013; Mehrpour,
Maryam/D-8640-2017; AUBERGER, Patrick/G-1491-2013; Martinet,
Wim/I-7375-2015; Chagin, Andrei/F-4080-2014; Che, Yongsheng/D-9840-2017;
Weis, Simone/F-5363-2014; Fukuda, MItsunori/I-1511-2015; Shiri-Sverdlov,
Ronit/E-5571-2017; Stork, Bjorn/C-2160-2011; Faculdade de Ciencias
Medicas, Nova Medical School/K-6209-2013; Casas, Josefina/L-7934-2014;
MECHTA-GRIGORIOU, Fatima/C-5253-2017; Cassinelli, Giuliana/K-7591-2016;
Uversky, Vladimir/F-4515-2011; Harrath, Abdel Halim/K-2166-2014;
Torgersen, Maria Lyngaas/F-3492-2017; Bettuzzi, Saverio/B-2609-2009;
PASQUET, JEAN-MAX/I-9702-2014; Cleyrat, Cedric/F-1824-2016; Pinto
Ribeiro Xavier, Cristina/C-7442-2015; Sedej, Simon/L-3066-2015;
Ureshino, Rodrigo/C-4095-2014; Pervaiz, Shazib/C-4188-2015; Yamanaka,
Koji/H-5806-2011; Smith, Duncan /C-6891-2011; Andrieu-Abadie,
Nathalie/N-6793-2013; Nunes dos Santos, Claudia/H-6476-2016;
OI Miranda-Vizuete, Antonio/0000-0002-6856-5396; Nezis,
Ioannis/0000-0003-0233-7574; Lemberg, Marius/0000-0002-0996-1268; Roue,
Gael/0000-0003-0245-2257; KIHARA, AKIO/0000-0001-5889-0788; Pardo,
Julian/0000-0003-0154-0730; White, Anthony/0000-0003-1802-9891; Bartel,
Bonnie/0000-0002-6367-346X; Travassos, Leonardo/0000-0003-1323-3797;
Fusco, Carmela/0000-0001-7794-6046; Xue, Yu/0000-0002-9403-6869; Ke,
Zun-Ji/0000-0003-4038-2456; Chiong, Mario/0000-0002-5174-6545; Penalva,
Miguel A/0000-0002-3102-2806; Pinton, Paolo/0000-0001-7108-6508; xia,
tian/0000-0003-0123-1305; Tettamanti, Gianluca/0000-0002-0665-828X;
Staels, Bart/0000-0002-3784-1503; Sasaki, Motoko/0000-0003-2514-760X;
Corazzari, Marco/0000-0002-6246-5968; Neves, Bruno/0000-0001-7391-3124;
Besteiro, Sebastien/0000-0003-1853-1494; Garcia-Macia,
Marina/0000-0002-3908-9060; Lopez-Otin, Carlos/0000-0001-6964-1904;
King, Jason/0000-0003-0596-4506; ZHUANG, Xiaohong/0000-0002-2480-8210;
Duran, Raul/0000-0002-2249-9215; Span, Paul/0000-0002-1930-6638; Lazo,
Pedro /0000-0001-8997-3025; antonioli, manuela/0000-0002-7568-4713;
Cenci, Simone/0000-0003-1215-7518; Milan, Enrico/0000-0003-3094-4275;
Pacelli, Consiglia/0000-0003-4915-5823; Moreira,
Paula/0000-0001-5177-6747; Gomez-Sanchez, Ruben/0000-0002-8274-3259;
Zhang, Li/0000-0002-1740-8833; Rimbach, Gerald/0000-0001-7888-4684;
Buchan, Alastair/0000-0002-2918-5200; Liu, Yule/0000-0002-4423-6045;
Viola, Giampietro/0000-0001-9329-165X; Knecht,
Erwin/0000-0002-7208-3832; Corti, Olga/0000-0003-2093-7389; Troncoso,
Rodrigo/0000-0003-0796-5908; Schwarten, Melanie/0000-0001-8920-9668;
Corasaniti, Maria Tiziana/0000-0001-6472-0697; Westermann,
Benedikt/0000-0002-2991-1604; Nakatogawa, Hitoshi/0000-0002-5828-0741;
Digard, Paul/0000-0002-0872-9440; Song, Jie/0000-0002-2461-3683; Oshima,
Shigeru/0000-0003-1186-9177; Mauvezin, Caroline/0000-0003-4220-7272;
Gotor, Cecilia/0000-0003-4272-7446; Fiorito,
Filomena/0000-0002-6658-7807; Giordano, Antonio/0000-0002-5959-016X;
Machado-Santelli, Glaucia /0000-0003-2046-9693; Cervia,
Davide/0000-0002-2727-9449; Li, Rui/0000-0002-7210-8358; Soenen,
Stefaan/0000-0003-2390-3133; Tapia, Jose/0000-0002-3614-6867; Wang,
Haichao/0000-0002-0211-9000; Gorski, Sharon/0000-0002-3821-8289;
Munoz-Pinedo, Cristina/0000-0002-9120-664X; Molinari,
Marco/0000-0001-9808-9688; Vitale, Giovanni/0000-0003-2478-683X;
Piacentini, Mauro/0000-0003-2919-1296; ferraro,
elisabetta/0000-0002-9596-4624; Nardacci, Roberta/0000-0002-9209-1207;
Chiacchiera, Fulvio/0000-0003-3830-2090; Sanchez-Prieto,
Ricardo/0000-0003-0882-9780; Facchiano, Antonio/0000-0002-4243-2392;
AQUILANO, KATIA/0000-0002-5905-9870; Ubukata,
Makoto/0000-0001-8911-2815; Poletti, Angelo/0000-0002-8883-0468; Liu,
Zexian/0000-0001-9698-0610; Szegezdi, Eva/0000-0002-5708-3535;
Rodrigues, Cecilia/0000-0002-4829-754X; LEE, Sung
Sik/0000-0001-9267-232X; Villar-Rayo, Marga/0000-0003-4172-9079;
Mizushima, Noboru/0000-0002-6258-6444; Segui-Simarro, Jose
M./0000-0001-7672-4169; Segura-Aguilar, Juan/0000-0002-1018-673X; Wang,
Chengshu/0000-0003-1477-1466; Viscomi, Maria Teresa/0000-0002-9096-4967;
Knavelsrud, Helene/0000-0001-8848-8829; trisciuoglio,
Daniela/0000-0002-7007-7914; De Santi, Mauro/0000-0003-2983-8344; Wu,
William K.K./0000-0002-5662-5240; GROS, Frederic/0000-0002-6252-4323;
Arimoto, Hirokazu/0000-0002-0086-6117; Jannig,
Paulo/0000-0002-2569-4091; Di Renzo, Livia/0000-0003-3807-0760; Clarke,
Robert/0000-0002-9278-0854; Morrison, Janna/0000-0002-8602-8519; Poirot,
Marc/0000-0002-5711-6624; Van Kaer, Luc/0000-0001-5275-2309; De Meyer,
Guido/0000-0003-3848-8702; Penninger, Josef/0000-0002-8194-3777;
Galluzzi, Luca/0000-0002-1747-526X; Goncalves,
Dawit/0000-0003-2621-3330; Sachse, Carsten/0000-0002-1168-5143; Koike,
Masato/0000-0002-3174-5684; Perez-Sala, Dolores/0000-0003-0600-665X;
Franco, Rodrigo/0000-0003-3241-8615; brest, patrick/0000-0002-1252-4747;
Revuelta, Jose/0000-0001-7838-5308; Berchem, Guy/0000-0003-0157-2257;
Kriston-Vizi, Janos/0000-0002-0149-145X; Kanki,
Tomotake/0000-0001-9646-5379; Jimenez, Alberto/0000-0003-3685-6479;
Martin-Acebes, Miguel/0000-0001-6015-3613; Esteban-Martinez,
Lorena/0000-0002-8163-6259; Guillen, Carlos/0000-0002-9370-6314; Zhang,
David/0000-0002-5027-5286; Awale, Suresh/0000-0002-5299-193X; Braus,
Gerhard/0000-0002-3117-5626; Folini, Marco/0000-0002-1811-4407; Fan,
Chunhai/0000-0002-7171-7338; Juhasz, Gabor/0000-0001-8548-8874; Wang, Yu
Tian/0000-0001-8592-0698; Minina, Elena/0000-0002-2619-1859; Dubey,
Vikash/0000-0002-4281-2504; Garg, Abhishek/0000-0002-9976-9922; Hill,
Bradford/0000-0001-5332-8286; AUBERGER, Patrick/0000-0002-2481-8275;
Chagin, Andrei/0000-0002-2696-5850; Stork, Bjorn/0000-0002-4167-7806;
MECHTA-GRIGORIOU, Fatima/0000-0002-3751-6989; Cassinelli,
Giuliana/0000-0003-4648-2562; Uversky, Vladimir/0000-0002-4037-5857;
Harrath, Abdel Halim/0000-0002-2170-1303; Torgersen, Maria
Lyngaas/0000-0003-2616-7194; Lee, Ju-hyun/0000-0002-0280-8375; Cleyrat,
Cedric/0000-0002-1928-6497; Pinto Ribeiro Xavier,
Cristina/0000-0002-4613-1917; Hernandez, Agustin/0000-0002-7884-8023;
Frankel, Lisa/0000-0001-7249-3607; Saveljeva,
Svetlana/0000-0002-0644-9752; malorni, walter/0000-0002-1223-7000;
Rouschop, Kasper/0000-0002-4208-5415; Sedej, Simon/0000-0002-4419-6821;
MORELLI, MARIA BEATRICE/0000-0002-4614-5649; Wright,
Karen/0000-0003-0040-9247; Wilkinson, Simon/0000-0003-1082-8218; Guerra,
Barbara/0000-0003-1136-2413; Bryson-Richardson,
Robert/0000-0002-9501-8208; Balduini, Walter/0000-0001-8438-9559; Wang,
Xuejun/0000-0001-9267-1343; Vieira, Helena/0000-0001-9415-3742; Rizzi,
Federica/0000-0002-6670-2588; pierre, philippe/0000-0003-0863-8255;
McInerney, Gerald/0000-0003-2257-7241; Isidoro,
Ciro/0000-0002-5494-3034; Pereira, Paulo/0000-0002-9908-2290; Ureshino,
Rodrigo/0000-0003-3371-3376; Cadwell, Ken/0000-0002-5860-0661;
BRANCOLINI, Claudio/0000-0002-6597-5373; Sigurdsson,
Einar/0000-0003-1451-0952; Duchen, Michael/0000-0003-2548-4294; Amelio,
Ivano/0000-0002-9126-5391; Malli, Roland/0000-0001-6327-8729; Zhou,
Guang-Zhou/0000-0003-3672-875X; Martens, Sascha/0000-0003-3786-8199;
Gavard, Julie/0000-0002-7985-9007; Rosenstiel,
Philip/0000-0002-9692-8828; Linkermann, Andreas/0000-0001-6287-9725;
Cianfanelli, Valentina/0000-0002-3857-9463; Lanzi,
Cinzia/0000-0002-4480-9413; Hoppe, Thorsten/0000-0002-4734-9352; MOREL,
Etienne/0000-0002-4763-4954; Kwok, Terry/0000-0002-5905-3233; Simonsen,
Anne/0000-0003-4711-7057; Cecconi, Francesco/0000-0002-5614-4359; Moris,
Arnaud/0000-0002-5052-1678; Harris, James/0000-0002-5634-9637; Romani,
Luigina/0000-0002-1356-525X; Velasco, Guillermo/0000-0002-1994-2386;
Bravo-San Pedro, Jose Manuel/0000-0002-5781-1133; Chieppa,
Marcello/0000-0001-9819-0823; Frigo, Daniel/0000-0002-0713-471X; Olsson,
Stefan/0000-0003-1931-9081; Cocco, Tiziana/0000-0001-7171-3460; Chang,
Chih-Peng/0000-0002-0061-3478; Dikic, Ivan/0000-0001-8156-9511; Norga,
Koenraad/0000-0002-9231-0350; Harris, Adrian/0000-0003-1376-8409;
Kaminskyy, Vitaliy/0000-0002-8151-5270; Qi, Xin/0000-0002-9578-3890;
Shiri-Sverdlov, Ronit/0000-0002-6736-7814; Schiavi,
Alfonso/0000-0002-6563-8035; Ketteler, Robin/0000-0002-2786-7291;
Salazar, Maria/0000-0001-6784-9541; CRIPPA, VALERIA/0000-0002-3058-5711;
Wu, Jian/0000-0001-9933-7364; Hilfiker, Sabine/0000-0002-5167-7682;
Hulmi, Juha/0000-0003-3813-2124; Fernandez-Checa, Jose
Carlos/0000-0003-3422-2990; Wong, Esther/0000-0003-2421-7346; Rudolf,
Ruediger/0000-0002-0833-1053; Zhu, Wei-Guo/0000-0001-8385-6581; Chen,
Quan/0000-0001-7539-8728; Yamanaka, Koji/0000-0003-4655-0035; Smith,
Duncan /0000-0002-6592-9852; Andrieu-Abadie,
Nathalie/0000-0003-2698-1970; Matsuura, Akira/0000-0002-2300-7227;
MacIntosh, Gustavo/0000-0003-1350-1229; Tripathi,
Durga/0000-0001-8736-4808; Hamann, Andrea/0000-0001-9821-7491; Nunes dos
Santos, Claudia/0000-0002-5809-1924; Rein, Theo/0000-0003-2850-4289
FU BLRD VA [I01 BX001746, I01 BX001969]; Biotechnology and Biological
Sciences Research Council [BBS/E/B/000C0413]; Cancer Research UK [11359,
12825, 12918]; Doris Duke Charitable Foundation [2014112]; Medical
Research Council [G0300648, G0601891, G0801936, G1000089, G1002186,
MC_U105185860, MC_U132670600, MC_UP_A500_1019, MC_UU_12016/4,
MC_UU_12022/6, MR/J010448/1, MR/L010933/1, MR/M00869X/1, MR/M019217/1,
MR/N004434/1]; NCCIH NIH HHS [R01 AT005076]; NCI NIH HHS [K08 CA164047,
K08 CA193982, K22 CA181274, P01 CA163200, P30 CA010815, R01 CA078810,
R01 CA089121, R01 CA130893, R01 CA140964, R01 CA142862, R01 CA143811,
R01 CA162405, R01 CA184137, R01 CA187305, R01 CA193698, T32 CA009686,
U54 CA149147]; NCRR NIH HHS [P20 RR024489]; NEI NIH HHS [R01 EY005681,
R01 EY009083, R01 EY010199, R01 EY013434, R01 EY015537, R01 EY018884,
R01 EY019643, R01 EY022633, R01 EY023512, R01 EY024327, R01 EY025362,
R21 EY026207]; NHLBI NIH HHS [R56 HL122580, P01 HL129941, R01 HL056416,
R01 HL059888, R01 HL071158, R01 HL072166, R01 HL072844, R01 HL079669,
R01 HL098216, R01 HL107594, R01 HL117913, R01 HL126711, R01 HL130174,
R01 HL130230, R01 HL130845]; NIA NIH HHS [K02 AG042095, P01 AG031782,
P30 AG028740, R00 AG042494, R00 AG048016, R01 AG020197, R01 AG031867,
R01 AG032611, R01 AG038664, R01 AG039756, R01 AG043517, R37 AG021904];
NIAAA NIH HHS [K01 AA019996, R01 AA019954, R01 AA022601]; NIAID NIH HHS
[R01 AI042999, R01 AI091968, R01 AI092084, R01 AI103197, R01 AI104928,
R01 AI108906, R01 AI111935, R21 AI115286]; NIAMS NIH HHS [R01 AR042527,
R01 AR050429, R01 AR060837, R01 AR062030, R21 AR060444]; NICHD NIH HHS
[U54 HD090255]; NIDDK NIH HHS [K01 DK075386, K08 DK089117, P01 DK098108,
P30 DK020541, P30 DK020572, P30 DK020593, R00 DK094980, R01 DK033823,
R01 DK044234, R01 DK061498, R01 DK062092, R01 DK073336, R01 DK076685,
R01 DK079879, R01 DK090115, R01 DK097441, R01 DK098331, R01 DK105118,
R01 DK107220, R03 DK089010, R03 DK106304, R03 DK106344, R21 DK075494,
R56 DK037034, R56 DK108921]; NIEHS NIH HHS [P30 ES006694, P30 ES023512];
NIGMS NIH HHS [GM053396, K12 GM068524, P20 GM103492, P20 GM103554, P20
GM103652, P20 GM104934, R01 GM021841, R01 GM053396, R01 GM060574, R01
GM061766, R01 GM063075, R01 GM101056, R01 GM114840, R01 GM116908]; NINDS
NIH HHS [K08 NS083739, K08 NS085324, R01 NS062792, R01 NS073813, R01
NS075685, R01 NS076896, R01 NS077239, R01 NS078072, R01 NS079697, R01
NS085070, R01 NS088192, R01 NS089737, R01 NS091218, R01 NS094527, R03
NS090939, R21 NS091928]; Parkinson's UK [F-1002, H-1201, K-1202];
Wellcome Trust [087518]; Worldwide Cancer Research [14-1328]
NR 2174
TC 332
Z9 341
U1 544
U2 899
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1554-8627
EI 1554-8635
J9 AUTOPHAGY
JI Autophagy
PY 2016
VL 12
IS 1
BP 1
EP 222
DI 10.1080/15548627.2015.1100356
PG 222
WC Cell Biology
SC Cell Biology
GA DI6FU
UT WOS:000373595400001
PM 26799652
ER
PT J
AU Warfel, JM
Zimmerman, LI
Merkel, TJ
AF Warfel, Jason M.
Zimmerman, Lindsey I.
Merkel, Tod J.
TI Comparison of Three Whole-Cell Pertussis Vaccines in the Baboon Model of
Pertussis
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID NONHUMAN PRIMATE MODEL; BORDETELLA-PERTUSSIS; CONTROLLED-TRIAL;
EFFICACY; EPIDEMIOLOGY; TRANSMISSION; VACCINATION; INFECTION; TEENAGERS;
RESPONSES
AB Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have escalated since the 1990s and reached a 50-year high of 48,000 cases in 2012. While this pertussis resurgence is not completely understood, we previously showed that the current acellular pertussis vaccines do not prevent colonization or transmission following challenge. In contrast, a whole-cell pertussis vaccine accelerated the rate of clearance compared to rates in unvaccinated animals and animals treated with the acellular vaccine. In order to understand if these results are generalizable, we used our baboon model to compare immunity from whole-cell vaccines from three different manufacturers that are approved outside the United States. We found that, compared to clearance rates with no vaccine and with an acellular pertussis vaccine, immunization with any of the three whole-cell vaccines significantly accelerated the clearance of B. pertussis following challenge. Whole-cell vaccination also significantly reduced the total nasopharyngeal B. pertussis burden, suggesting that these vaccines reduce the opportunity for pertussis transmission. Meanwhile, there was no difference in either the duration or in B. pertussis burden between unvaccinated and acellular-pertussis-vaccinated animals, while previously infected animals were not colonized following reinfection. We also determined that transcription of the gene encoding interleukin-17 (IL-17) was increased in whole-cell-vaccinated and previously infected animals but not in acellular-pertussis-vaccinated animals following challenge. Together with our previous findings, these data are consistent with a role for Th17 responses in the clearance of B. pertussis infection.
C1 [Warfel, Jason M.; Zimmerman, Lindsey I.; Merkel, Tod J.] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
RP Merkel, TJ (reprint author), US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
EM tod.merkel@fda.hhs.gov
FU Food and Drug Administration; NIH/NIAID [Y1-AI-1727-01]; National
Institutes of Health National Center for Research Resources
[P40RR012317, 5R24RR016556-10]
FX This work was funded by the Food and Drug Administration and NIH/NIAID
through interagency agreement number Y1-AI-1727-01. Baboons were
obtained from the Oklahoma Baboon Research Resource. The Oklahoma Baboon
Research Resource was supported by grant numbers P40RR012317 and
5R24RR016556-10 from the National Institutes of Health National Center
for Research Resources.
NR 34
TC 2
Z9 2
U1 2
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
EI 1556-679X
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD JAN
PY 2016
VL 23
IS 1
BP 47
EP 54
DI 10.1128/CVI.00449-15
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DI4RY
UT WOS:000373488200007
ER
PT J
AU Gormley, NJ
Turley, DM
Dickey, JS
Farrell, AT
Reaman, GH
Stafford, E
Carrington, L
Marti, GE
AF Gormley, Nicole J.
Turley, Danielle M.
Dickey, Jennifer S.
Farrell, Ann T.
Reaman, Gregory H.
Stafford, Elizabeth
Carrington, Lea
Marti, Gerald E.
TI Regulatory Perspective on Minimal Residual Disease Flow Cytometry
Testing in Multiple Myeloma
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Article
DE MRD; MM; FDA; B cells; flow cytometry; hematology
ID ASSAYS PRACTICE GUIDELINES; VALIDATION; ICSH; ICCS; TRANSPLANTATION;
COMBINATION; PROTOCOLS; STRATEGY; CRITERIA; PROGRAM
AB The FDA has co-sponsored three workshops to address minimal residual disease (MRD) detection in acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and acute myeloid leukemia (AML) as well as an FDA-NCI roundtable symposium on MRD detection and its use as a response biomarker in Multiple Myeloma (MM). As clinical outcomes in MM continue to improve with the introduction of new therapeutics, consideration of biomarkers and their development as validated surrogate endpoints that can be used in the place of traditional clinical trial endpoints of progression-free survival (PFS) will be fundamental to expeditious drug development. This article will describe the FDA drug approval process, the regulatory framework through which a biomarker can be used as a surrogate endpoint for drug approval, and how MRD detection in MM fits within this context. In parallel, this article will also describe the FDA current device clearance process with emphasis on the analytical development as it might apply to an in vitro diagnostic assay for the detection of MRD in MM. It is anticipated that this Special Issue may possibly represent how MRD might serve as a drug development tool in hematological malignancies. (C) 2015 International Clinical Cytometry Society
C1 Food & Drug Adm, Ctr Drug Evaluat & Res, Rome, Italy.
Food & Drug Adm, Ctr Devices & Radiol Hlth, Rome, Italy.
RP Marti, GE (reprint author), CDRH FDA, Silver Spring, MD USA.
EM gerald.marti@fda.hhs.gov
NR 30
TC 3
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4949
EI 1552-4957
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD JAN
PY 2016
VL 90
IS 1
SI SI
BP 73
EP 80
DI 10.1002/cyto.b.21268
PG 8
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA DI3EK
UT WOS:000373381000011
PM 26108351
ER
PT J
AU Oliveira, AF
Landero, J
Kubachka, K
Nogueira, ARA
Zanetti, MA
Caruso, J
AF Oliveira, A. F.
Landero, J.
Kubachka, K.
Nogueira, A. R. A.
Zanetti, M. A.
Caruso, J.
TI Development and application of a selenium speciation method in cattle
feed and beef samples using HPLC-ICP-MS: evaluating the selenium
metabolic process in cattle
SO JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY
LA English
DT Article
ID INDUCTIVELY-COUPLED PLASMA; MASS-SPECTROMETRIC DETECTION; SIZE-EXCLUSION
CHROMATOGRAPHY; HUMAN HEALTH; DAIRY-COWS; RICH YEAST; SUPPLEMENTATION;
SELENOCYSTEINE; METHIONINE; TOXICITY
AB Selenium (Se) is an essential element for mammals with diet being the major source of intake. For this work cattle feed was enriched with combinations of selenium enriched yeast, canola oil, and/or vitamin E in order to evaluate the accumulation and metabolism of selenium in beef cattle. A method to identify and/or quantify the selenium species: selenocystine (SeCys(2)), selenomethionine (SeMet), selenomethionine-Se-oxide (SeOMet), and inorganic selenium species, selenate (Se(VI)) and selenite (Se(IV)), was developed and applied to cattle feed and beef samples.
C1 [Oliveira, A. F.] Univ Fed Sao Carlos, Dept Chem, Grp Appl Instrumental Anal, BR-13565905 Sao Carlos, SP, Brazil.
[Oliveira, A. F.; Nogueira, A. R. A.] Embrapa Southeast Livestock, BR-13560970 Sao Carlos, SP, Brazil.
[Oliveira, A. F.; Landero, J.; Caruso, J.] McMicken Coll Arts & Sci, Dept Chem, ML0172, Cincinnati, OH 45221 USA.
[Kubachka, K.] US FDA, Forens Chem Ctr, Cincinnati, OH USA.
[Zanetti, M. A.] Univ Sao Paulo, Fac Anim Sci & Food Engn, Dept Anim Sci, BR-13630000 Pirassununga, SP, Brazil.
RP Kubachka, K (reprint author), US FDA, Forens Chem Ctr, Cincinnati, OH USA.
EM kevin.kubachka@fda.hhs.gov
RI ZANETTI, MARCUS/F-3179-2012; Fernandes de Oliveira, Aline/D-1050-2015;
Nogueira, Ana Rita/D-9319-2012
OI ZANETTI, MARCUS/0000-0002-3778-0210; Fernandes de Oliveira,
Aline/0000-0002-4327-7064; Nogueira, Ana Rita/0000-0003-3648-2956
FU Coordenadoria de Aperfeicoamento Pessoal de Nivel Superior (CAPES)
[001/2011, 99999.014317/2013-03]
FX The authors would like to acknowledge Coordenadoria de Aperfeicoamento
Pessoal de Nivel Superior (CAPES) for financial support of this study
through the projects Capes/Embrapa 001/2011 and 99999.014317/2013-03 and
Agilent Technologies for providing the ICP-QQQ instrumentation loan.
NR 31
TC 1
Z9 1
U1 17
U2 31
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 0267-9477
EI 1364-5544
J9 J ANAL ATOM SPECTROM
JI J. Anal. At. Spectrom.
PY 2016
VL 31
IS 4
BP 1034
EP 1040
DI 10.1039/c5ja00330j
PG 7
WC Chemistry, Analytical; Spectroscopy
SC Chemistry; Spectroscopy
GA DI4LC
UT WOS:000373470400020
ER
PT S
AU Rahman, MA
Shen, MY
Dong, X
Lin, KK
Tsong, Y
AF Rahman, Mohammad Atiar
Shen, Meiyu
Dong, Xiaoyu (Cassie)
Lin, Karl K.
Tsong, Yi
BE Zhang, L
TI Regulatory Nonclinical Statistics
SO NONCLINICAL STATISTICS FOR PHARMACEUTICAL AND BIOTECHNOLOGY INDUSTRIES
SE Statistics for Biology and Health
LA English
DT Article; Book Chapter
DE Chemistry manufacturing; and control; Acceptance sampling; Content
uniformity; Pharmacological/toxicological studies
AB The nonclinical statistics teams in the Center of Drug Review and Research of the Food and Drug Administration (FDA) conduct regulatory reviews, statistical consultation, and statistical methodology development in nonclinical regulations. In this chapter, we provide a brief description of the two teams and provide two examples in statistical research development. In the first example, we describe the historical background and evolution of statistical methodology development in the last 20 years for the acceptance sampling and lot evaluation procedures on dose content uniformity involved with FDA Chemistry Manufacturing, and Control (CMC) Statistics Team. In the second example, we illustrate the research activities of Pharmacological/Toxicological (Pharm-Tox) Statistics Team at FDA with the background and evaluation of multiple pairwise comparisons in animal carcinogenetic studies.
C1 [Rahman, Mohammad Atiar; Shen, Meiyu; Dong, Xiaoyu (Cassie); Lin, Karl K.; Tsong, Yi] US FDA, Div Biometr 6, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
RP Tsong, Y (reprint author), US FDA, Div Biometr 6, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM yi.tsong@fda.hhs.gov
NR 11
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1431-8776
BN 978-3-319-23558-5; 978-3-319-23557-8
J9 STAT BIOL HEALTH
JI Stat. Biol. Health
PY 2016
BP 19
EP 31
DI 10.1007/978-3-319-23558-5_2
D2 10.1007/978-3-319-23558-5
PG 13
WC Biotechnology & Applied Microbiology; Mathematical & Computational
Biology; Pharmacology & Pharmacy; Statistics & Probability
SC Biotechnology & Applied Microbiology; Mathematical & Computational
Biology; Pharmacology & Pharmacy; Mathematics
GA BE5YU
UT WOS:000373682200003
ER
PT S
AU Lin, KK
Jackson, MT
Min, M
Rahman, MA
Thomson, SF
AF Lin, Karl K.
Jackson, Matthew T.
Min, Min
Rahman, Mohammad Atiar
Thomson, Steven F.
BE Zhang, L
TI Recent Research Projects by the FDA's Pharmacology and Toxicology
Statistics Team
SO NONCLINICAL STATISTICS FOR PHARMACEUTICAL AND BIOTECHNOLOGY INDUSTRIES
SE Statistics for Biology and Health
LA English
DT Article; Book Chapter
DE Bayesian methods in nonclinical biostatistics; Carcinogenicity studies;
Consumer's risk; Exact poly-3 trend tests; Experimental designs; Finite
dimensional logistic model; Finite dimensional proportional; Hazards
model; Multiplicity adjustment; Nonparametric Bayesian analysis;
Permutational distribution; Producer's risk
ID FALSE-POSITIVE RATES; DUAL CONTROL-GROUPS; ANIMAL CARCINOGENICITY;
TESTS; DESIGN; TREND; DISTRIBUTIONS; MORTALITY; BIOASSAY; ONSET
AB In addition to regular review work, the Pharmacology and Toxicology Statistics Team in CDER/FDA is actively engaged in a number of research projects. In this chapter we summarize some of our recent investigations and findings.
We have conducted a simulation study (discussed in Sect. 12.2) to evaluate the increase in Type 2 error attributable to the adoption by some non-statistical scientists within the agency of more stringent decision criteria than those we have recommended for the determination of statistically significant carcinogenicity findings in long term rodent bioassays. In many cases, the probability of a Type 2 error is inflated by a factor of 1: 5 or more.
A second simulation study (Sect. 12.3) has found that both the Type 1 and Type 2 error rates are highly sensitive to experimental design. In particular, designs using a dual vehicle control group are more powerful than designs using the same number of animals but a single vehicle control group, but this increase in power comes at the expense of a greatly inflated Type 1 error rate.
Since the column totals of the tables of permutations of animals to treatment groups cannot be presumed to be fixed, the exact methods used in the Cochran-Armitage test are not applicable to the poly-k test for trend. Section 12.4 presents simple examples showing all possible permutations of animals, and procedures for computing the probabilities of the individual permutations to obtain the exact p-values. Section 12.5 builds on this by proposing an exact ratio poly-k test method using samples of possible permutations of animals. The proposed ratio poly-k test does not assume fixed column sums and uses the procedure in Bieler and Williams (Biometrics 49(3): 793-801, 1993) to obtain the null variance estimate of the adjusted quantal tumor response estimate. Results of simulations show that the modified exact poly-3 method has similar sizes and levels of power compared to the method proposed in Mancuso et al. (Biometrics 58: 403-412, 2002) that also uses samples of permutations but uses the binomial null variance estimate of the adjusted response rates and is based on the assumption of fixed column sums.
Bayesians attempt to model not only the statistical data generating process as in the frequentist statistics, but also to model knowledge about the parameters governing that process. Section 12.6 includes a short review of possible reasons for adopting a Bayesian approach, and examples of survival and carcinogenicity analyses.
C1 [Lin, Karl K.; Min, Min; Rahman, Mohammad Atiar; Thomson, Steven F.] US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Biostat,Div Biometr 6, Silver Spring, MD USA.
[Jackson, Matthew T.] FDA CDER OTS OB DB6, Silver Spring, MD USA.
RP Lin, KK (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Biostat,Div Biometr 6, Silver Spring, MD USA.
EM karl.lin@fda.hhs.gov
NR 50
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER INT PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1431-8776
BN 978-3-319-23558-5; 978-3-319-23557-8
J9 STAT BIOL HEALTH
JI Stat. Biol. Health
PY 2016
BP 295
EP 348
DI 10.1007/978-3-319-23558-5_12
D2 10.1007/978-3-319-23558-5
PG 54
WC Biotechnology & Applied Microbiology; Mathematical & Computational
Biology; Pharmacology & Pharmacy; Statistics & Probability
SC Biotechnology & Applied Microbiology; Mathematical & Computational
Biology; Pharmacology & Pharmacy; Mathematics
GA BE5YU
UT WOS:000373682200013
ER
PT J
AU Lambertini, E
Buchanan, RL
Narrod, C
Pradhan, AK
AF Lambertini, Elisabetta
Buchanan, Robert L.
Narrod, Clare
Pradhan, Abani K.
TI Transmission of Bacterial Zoonotic Pathogens between Pets and Humans:
The Role of Pet Food
SO CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
LA English
DT Review
DE Zoonotic pathogens; pet food; pets; Salmonella; risk assessment;
household exposure
ID RESISTANT STAPHYLOCOCCUS-AUREUS; ESCHERICHIA-COLI O157; APPARENTLY
HEALTHY DOGS; POWDERED INFANT FORMULA; REPUBLIC-OF-IRELAND;
SALMONELLA-TYPHIMURIUM DT104; ENTERICA SEROVAR ENTERITIDIS;
HEMOLYTIC-UREMIC SYNDROME; RENDERED ANIMAL PRODUCTS; STAINLESS-STEEL
SURFACES
AB Recent Salmonella outbreaks associated with dry pet food and treats raised the level of concern for these products as vehicle of pathogen exposure for both pets and their owners. The need to characterize the microbiological and risk profiles of this class of products is currently not supported by sufficient specific data. This systematic review summarizes existing data on the main variables needed to support an ingredients-to-consumer quantitative risk model to (1) describe the microbial ecology of bacterial pathogens in the dry pet food production chain, (2) estimate pet exposure to pathogens through dry food consumption, and (3) assess human exposure and illness incidence due to contact with pet food and pets in the household. Risk models populated with the data here summarized will provide a tool to quantitatively address the emerging public health concerns associated with pet food and the effectiveness of mitigation measures. Results of such models can provide a basis for improvements in production processes, risk communication to consumers, and regulatory action.
C1 [Lambertini, Elisabetta; Buchanan, Robert L.; Pradhan, Abani K.] Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA.
[Lambertini, Elisabetta; Buchanan, Robert L.; Pradhan, Abani K.] Univ Maryland, Ctr Food Safety & Secur Syst, College Pk, MD 20742 USA.
[Narrod, Clare] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA.
RP Pradhan, AK (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA.
EM akp@umd.edu
NR 607
TC 2
Z9 2
U1 7
U2 20
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1040-8398
EI 1549-7852
J9 CRIT REV FOOD SCI
JI Crit. Rev. Food Sci. Nutr.
PY 2016
VL 56
IS 3
BP 364
EP 418
DI 10.1080/10408398.2014.902356
PG 55
WC Food Science & Technology; Nutrition & Dietetics
SC Food Science & Technology; Nutrition & Dietetics
GA DH6EK
UT WOS:000372883600003
PM 25875576
ER
PT J
AU Ehlers, T
Furness, S
Robinson, TP
Zhong, HZA
Goldsmith, D
Aribser, J
Bowen, JP
AF Ehlers, Tedman
Furness, Scott
Robinson, Thomas Philip
Zhong, Haizhen A.
Goldsmith, David
Aribser, Jack
Bowen, J. Phillip
TI Methionine AminoPeptidase Type-2 Inhibitors Targeting Angiogenesis
SO CURRENT TOPICS IN MEDICINAL CHEMISTRY
LA English
DT Review
DE ADME; Angiogenesis; Angiogenic inhibitors; Anti-angiogenic compounds;
Cancer; Drug design; Fumagillin; Methionine aminiopeptidase; MetAP-2;
Ovalicin; Pharmacophore; Cancer; TNP-470
ID SOLID TUMORS; PHASE-I; CLINICAL-APPLICATIONS; RHEUMATOID-ARTHRITIS;
FUMAGILLIN ANALOGS; SYNTHETIC ANALOGS; STRUCTURAL BASIS; FORCE-FIELD;
TNP-470; CANCER
AB Angiogenesis has been identified as a crucial process in the development and spread of cancers. There are many regulators of angiogenesis which are not yet fully understood. Methionine aminiopeptidase is a metalloenzyme with two structurally distinct forms in humans, Type-1 (MetAP-1) and Type-2 (MetAP-2). It has been shown that small molecule inhibitors of MetAP-2 suppress endothelial cell proliferation. The initial discovery by Donald Ingber of MetAP-2 inhibition as a potential target in angiogenesis began with a fortuitous observation similar to the discovery of penicillin activity by Sir Alexander Fleming. From a drug design perspective, MetAP-2 is an attractive target. Fumagillin and ovalicin, known natural products, bind with IC50 values in low nanomolar concentrations. Crystal structures of the bound complexes provide 3-dimensional coordinates for advanced computational studies. More recent discoveries have shown other biological activities for MetAP-2 inhibition, which has generated new interests in the design of novel inhibitors. Semisynthetic fumagillin derivatives such as AGM-1470 (TNP-470) have been shown to have better drug properties, but have not been very successful in clinical trials. The rationale and development of novel multicyclic analogs of fumagillin are reviewed.
C1 [Bowen, J. Phillip] Mercer Univ, Coll Pharm, Dpt Pharmaceut Sci, Ctr Drug Design, 3001 Mercer Univ Dr, Atlanta, GA 30341 USA.
[Ehlers, Tedman] BIOVIA Corp, Dassault Syst, 5005 Wateridge Vista Dr, San Diego, CA 92121 USA.
[Furness, Scott] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Qual, Off New Drug Prod, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
[Robinson, Thomas Philip] Univ Georgia, Dept Chem, Athens, GA 30602 USA.
[Zhong, Haizhen A.] Univ Nebraska, Dept Chem, 6001 Dodge St, Omaha, NE 68182 USA.
[Goldsmith, David] Emory Univ, Dept Chem, 1515 Pierce Dr, Atlanta, GA 30322 USA.
[Aribser, Jack] Emory Univ, Sch Med, Atlanta Vet Affairs Med Ctr, 5007 Woodruff Mem Bldg, Atlanta, GA 30322 USA.
[Aribser, Jack] Emory Univ, Sch Med, Dept Dermatol, 5007 Woodruff Mem Bldg, Atlanta, GA 30322 USA.
RP Bowen, JP (reprint author), Mercer Univ, Coll Pharm, Dpt Pharmaceut Sci, Ctr Drug Design, 3001 Mercer Univ Dr, Atlanta, GA 30341 USA.
EM bowen_jp@mercer.edu
NR 59
TC 3
Z9 3
U1 6
U2 9
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1568-0266
EI 1873-5294
J9 CURR TOP MED CHEM
JI Curr. Top. Med. Chem.
PY 2016
VL 16
IS 13
BP 1478
EP 1488
DI 10.2174/1568026615666150915121204
PG 11
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA DH5RL
UT WOS:000372849400007
PM 26369821
ER
PT J
AU Gieseker, CM
Crosby, TC
Mayer, TD
Bodeis, SM
Stine, CB
AF Gieseker, Charles M.
Crosby, Tina C.
Mayer, Tamara D.
Bodeis, Sonya M.
Stine, Cynthia B.
TI Development of Similar Broth Microdilution Methods to Determine the
Antimicrobial Susceptibility of Flavobacterium columnare and
F-psychrophilum
SO JOURNAL OF AQUATIC ANIMAL HEALTH
LA English
DT Article
ID MINIMUM INHIBITORY CONCENTRATIONS; IN-VITRO ACTIVITY; RAINBOW-TROUT;
CYTOPHAGA PSYCHROPHILA; BIOFILM FORMATION; ESCHERICHIA-COLI; AQUATIC
BACTERIA; MAGNESIUM-IONS; RESISTANCE; IDENTIFICATION
AB Flavobacterium columnare and F. psychrophilum are major fish pathogens that cause diseases that may require antimicrobial therapy. Choice of appropriate treatment is dependent upon determining the antimicrobial susceptibility of isolates. Therefore we optimized methods for broth microdilution testing of F. columnare and F. psychrophilum to facilitate standardizing an antimicrobial susceptibility test. We developed adaptations to make reproducible broth inoculums and confirmed the proper incubation time and media composition. We tested the stability of potential quality-control bacteria and compared test results between different operators. Log phase occurred at 48 h for F. columnare and 72-96 h for F. psychrophilum, confirming the test should be incubated at 28 degrees C for approximately 48 h and at 18 degrees C for approximately 96 h, respectively. The most consistent susceptibility results were achieved with plain, 4-g/L, dilute Mueller-Hinton broth supplemented with dilute calcium and magnesium. Supplementing the broth with horse serum did not improve growth. The quality-control strains, Escherichia coli ATCC 25922 and Aeromonas salmonicida subsp. salmonicida ATCC 33658, yielded stable minimal inhibitory concentrations (MIC) against all seven antimicrobials tested after 30 passes at 28 degrees C and 15 passes at 18 degrees C. In comparison tests, most MICs of the isolates agreed 100% within one drug dilution for ampicillin, florfenicol, and oxytetracycline. The agreement was lower with the ormetoprim-sulfdimethoxine combination, but there was at least 75% agreement for all but one isolate. These experiments have provided methods to help standardize antimicrobial susceptibility testing of these nutritionally fastidious aquatic bacteria.
C1 [Gieseker, Charles M.; Crosby, Tina C.; Mayer, Tamara D.; Bodeis, Sonya M.; Stine, Cynthia B.] US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA.
[Mayer, Tamara D.] Sirenas Marine Discovery, 3550 Gen Atom Court, San Diego, CA 92121 USA.
RP Gieseker, CM (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA.
EM charles.gieseker@fda.hhs.gov
NR 29
TC 0
Z9 0
U1 2
U2 8
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0899-7659
EI 1548-8667
J9 J AQUAT ANIM HEALTH
JI J. Aquat. Anim. Health
PY 2016
VL 28
IS 1
BP 27
EP 38
DI 10.1080/08997659.2015.1105878
PG 12
WC Fisheries; Veterinary Sciences
SC Fisheries; Veterinary Sciences
GA DH7IW
UT WOS:000372968000004
PM 26949840
ER
PT J
AU Guan, A
Wang, Y
Phillips, KS
Li, ZY
AF Guan, Allan
Wang, Yi
Phillips, K. Scott
Li, Zhenyu
TI A contact-lens-on-a-chip companion diagnostic tool for personalized
medicine
SO LAB ON A CHIP
LA English
DT Article
ID PSEUDOMONAS-AERUGINOSA; HYDROGEL MATERIALS; CARE SOLUTIONS; HUMAN TEAR;
PROTEIN; DEPOSITION; VARIABILITY; BIOFILMS
AB We present a novel, microfluidic platform that integrates human tears (1 mu L) with commercial contact lens materials to provide personalized assessment of lens care solution performance. This device enabled the detection of significant differences in cleaning and disinfection outcomes between subjects and between biofilms vs. planktonic bacteria.
C1 [Guan, Allan; Li, Zhenyu] George Washington Univ, Dept Biomed Engn, 800 22nd St NW, Washington, DC 20052 USA.
[Wang, Yi; Phillips, K. Scott] US FDA, Div Biol Chem & Mat Sci, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
RP Li, ZY (reprint author), George Washington Univ, Dept Biomed Engn, 800 22nd St NW, Washington, DC 20052 USA.; Phillips, KS (reprint author), US FDA, Div Biol Chem & Mat Sci, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM Kenneth.Phillips@fda.hhs.gov; zhenyu@gwu.edu
RI phillips, kenneth/F-7560-2014
OI phillips, kenneth/0000-0002-6552-0694
FU FDA Medical Countermeasures Initiative; FDA Office of Women's Health
FX Parts of this work were supported by the FDA Medical Countermeasures
Initiative and the FDA Office of Women's Health. This project was
supported in part by an appointment to the ORISE Research Participation
Program at the CDRH, U.S. Food and Drug Administration, administered by
the Oak Ridge Institute for Science and Education through an
inter-agency agreement between the U.S. Department of Energy and
FDA/CDRH.
NR 31
TC 0
Z9 0
U1 1
U2 11
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1473-0197
EI 1473-0189
J9 LAB CHIP
JI Lab Chip
PY 2016
VL 16
IS 7
BP 1152
EP 1156
DI 10.1039/c6lc00034g
PG 5
WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience
& Nanotechnology
SC Biochemistry & Molecular Biology; Chemistry; Science & Technology -
Other Topics
GA DH8PR
UT WOS:000373057400005
PM 26923038
ER
PT J
AU Baer, B
Nguyen, M
Wool, EJ
Winiecki, S
Scott, J
Martini, D
Botsis, T
Balls, R
AF Baer, B.
Nguyen, M.
Wool, E. J.
Winiecki, S.
Scott, J.
Martini, D.
Botsis, T.
Balls, R.
TI Can Natural Language Processing Improve the Efficiency of Vaccine
Adverse Event Report Review?
SO METHODS OF INFORMATION IN MEDICINE
LA English
DT Review
DE Biosurveillance; product surveillance; post-marketing; data mining;
natural language processing
ID GUILLAIN-BARRE-SYNDROME; TEXT MINING SYSTEM; EXTRACTION SYSTEM; CASE
DEFINITIONS; INFORMATION
AB Background: Individual case review of spontaneous adverse event (AE) reports remains a cornerstone of medical product safety surveillance for industry and regulators. Previously we developed the Vaccine Adverse Event Text Miner (VaeTM) to offer automated information extraction and potentially accelerate the evaluation of large volumes of unstructured data and facilitate signal detection.
Objective: To assess how the information extraction performed by VaeTM impacts the accuracy of a medical expert's review of the vaccine adverse event report.
Methods: The "outcome of interest" (diagnosis, cause of death, second level diagnosis), "onset time," and "alternative explanations" (drug, medical and family history) for the adverse event were extracted from 1000 reports from the Vaccine Adverse Event Reporting System (VAERS) using the VaeTM system. We compared the human interpretation, by medical experts, of the VaeTM extracted data with their interpretation of the traditional full text reports for these three variables. Two experienced clinicians alternately reviewed text miner output and full text. A third clinician scored the match rate using a predefined algorithm; the proportion of matches and 95% confidence intervals (CI) were calculated. Review time per report was analyzed.
Results: Proportion of matches between the interpretation of the VaeTM extracted data, compared to the interpretation of the full text: 93% for outcome of interest (95% CI: 91-94%) and 78% for alternative explanation (95% CI: 75-81%). Extracted data on the time to onset was used in 14% of cases and was a match in 54% (95% CI: 46-63%) of those cases. When supported by structured time data from reports, the match for time to onset was 79% (95% CI: 76-81%). The extracted text averaged 136 (74%) fewer words, resulting in a mean reduction in review time of 50 (58%) seconds per report.
Conclusion: Despite a 74% reduction in words, the clinical conclusion from VaeTM extracted data agreed with the full text in 93% and 78% of reports for the outcome of interest and alternative explanation, respectively. The limited amount of extracted time interval data indicates the need for further development of this feature. VaeTM may improve review efficiency, but further study is needed to determine if this level of agreement is sufficient for routine use.
C1 [Baer, B.; Nguyen, M.; Wool, E. J.; Winiecki, S.; Scott, J.; Martini, D.; Botsis, T.; Balls, R.] US FDA, Off Biostat & Epidemiol, CBER, Rockville, MD 20857 USA.
[Botsis, T.] Univ Tromso, Dept Comp Sci, Tromso, Norway.
RP Baer, B (reprint author), US FDA, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave,W071-1323, Silver Spring, MD 20993 USA.
EM bethany.baer@fda.hhs.gov
NR 23
TC 0
Z9 0
U1 3
U2 4
PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN
PI STUTTGART
PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY
SN 0026-1270
J9 METHOD INFORM MED
JI Methods Inf. Med.
PY 2016
VL 55
IS 2
BP 144
EP 150
DI 10.3414/ME14-01-0066
PG 7
WC Computer Science, Information Systems; Health Care Sciences & Services;
Medical Informatics
SC Computer Science; Health Care Sciences & Services; Medical Informatics
GA DH7BC
UT WOS:000372945200005
PM 26394725
ER
PT J
AU Fiuza, JA
Dey, R
Davenport, D
Abdeladhim, M
Meneses, C
Oliveira, F
Kamhawi, S
Valenzuela, JG
Gannavaram, S
Nakhasi, HL
AF Fiuza, Jacqueline Araujo
Dey, Ranadhir
Davenport, Dwann
Abdeladhim, Maha
Meneses, Claudio
Oliveira, Fabiano
Kamhawi, Shaden
Valenzuela, Jesus G.
Gannavaram, Sreenivas
Nakhasi, Hira L.
TI Intradermal Immunization of Leishmania donovani Centrin Knock-Out
Parasites in Combination with Salivary Protein LJM19 from Sand Fly
Vector Induces a Durable Protective Immune Response in Hamsters
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID EXPERIMENTAL VISCERAL LEISHMANIASIS; LUTZOMYIA-LONGIPALPIS SALIVA;
DELETED PARASITES; VACCINATION; MEXICANA; CELLS; INFECTIONS; INFANTUM;
MICE; INTERLEUKIN-12
AB Background
Visceral leishmaniasis (VL) is a neglected tropical disease and is fatal if untreated. There is no vaccine available against leishmaniasis. The majority of patients with cutaneous leishmaniasis (CL) or VL develop a long-term protective immunity after cure from infection, which indicates that development of an effective vaccine against leishmaniasis is possible. Such protection may also be achieved by immunization with live attenuated parasites that do not cause disease. We have previously reported a protective response in mice, hamsters and dogs with Leishmania donovani centrin gene knock-out parasites (LdCen(-/-)), a live attenuated parasite with a cell division specific centrin1 gene deletion. In this study we have explored the effects of salivary protein LJM19 as an adjuvant and intradermal (ID) route of immunization on the efficacy of LdCen(-/-) parasites as a vaccine against virulent L. donovani.
Methodology/Principal Findings
To explore the potential of a combination of LdCen(-/-) parasites and salivary protein LJM19 as vaccine antigens, LdCen(-/-) ID immunization followed by ID challenge with virulent L. donovani were performed in hamsters in a 9-month follow up study. We determined parasite burden (serial dilution), antibody production (ELISA) and cytokine expression (qPCR) in these animals. Compared to controls, animals immunized with LdCen(-/-) + LJM19 induced a strong antibody response, a reduction in spleen and liver parasite burden and a higher expression of pro-inflammatory cytokines after immunization and one month post-challenge. Additionally, a low parasite load in lymph nodes, spleen and liver, and a non-inflamed spleen was observed in immunized animals 9 months after the challenge infection.
Conclusions
Our results demonstrate that an ID vaccination using LdCen(-/-) parasites in combination with sand fly salivary protein LJM19 has the capability to confer long lasting protection against visceral leishmaniasis that is comparable to intravenous or intracardial immunization.
C1 [Fiuza, Jacqueline Araujo; Dey, Ranadhir; Davenport, Dwann; Gannavaram, Sreenivas; Nakhasi, Hira L.] US FDA, Lab Emerging Pathogens, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
[Fiuza, Jacqueline Araujo] Ctr Pesquisas Rene Rachou Fiocruz Minas, Lab Imunol Celular & Mol, Belo Horizonte, MG, Brazil.
[Abdeladhim, Maha; Meneses, Claudio; Oliveira, Fabiano; Kamhawi, Shaden; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
RP Gannavaram, S; Nakhasi, HL (reprint author), US FDA, Lab Emerging Pathogens, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
EM sreenivas.gannavaram@fda.hhs.gov; hira.nakhasi@fda.hhs.gov
FU Intramural Research Program at National Institute of Allergy and
Infectious Diseases, NIH; Center for Biologics Evaluation and Research,
FDA
FX This research was supported in part by the Intramural Research Program
at the National Institute of Allergy and Infectious Diseases, NIH (JGV
SK FO MA) and Center for Biologics Evaluation and Research, FDA (JAF RD
SG HLN). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 53
TC 3
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U1 2
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD JAN
PY 2016
VL 10
IS 1
AR e0004322
DI 10.1371/journal.pntd.0004322
PG 17
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DH1SR
UT WOS:000372565700035
PM 26752686
ER
PT J
AU Udoko, AN
Johnson, CA
Dykan, A
Rachakonda, G
Villalta, F
Mandape, SN
Lima, MF
Pratap, S
Nde, PN
AF Udoko, Aniekanabassi N.
Johnson, Candice A.
Dykan, Andrey
Rachakonda, Girish
Villalta, Fernando
Mandape, Sammed N.
Lima, Maria F.
Pratap, Siddharth
Nde, Pius N.
TI Early Regulation of Profibrotic Genes in Primary Human Cardiac Myocytes
by Trypanosoma cruzi
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID GROWTH-FACTOR-BETA; CHAGAS-DISEASE; UNITED-STATES; EXTRACELLULAR-MATRIX;
MYOCARDIAL FIBROSIS; TISSUE FIBROSIS; EARLY INFECTION; DUAL ROLE;
HYPERTROPHY; EXPRESSION
AB The molecular mechanisms of Trypanosoma cruzi induced cardiac fibrosis remains to be elucidated. Primary human cardiomyoctes (PHCM) exposed to invasive T. cruzi trypomastigotes were used for transcriptome profiling and downstream bioinformatic analysis to determine fibrotic-associated genes regulated early during infection process (0 to 120 minutes). The identification of early molecular host responses to T. cruzi infection can be exploited to delineate important molecular signatures that can be used for the classification of Chagasic patients at risk of developing heart disease. Our results show distinct gene network architecture with multiple gene networks modulated by the parasite with an incline towards progression to a fibrogenic phenotype. Early during infection, T. cruzi significantly upregulated transcription factors including activator protein 1 (AP1) transcription factor network components (including FOSB, FOS and JUNB), early growth response proteins 1 and 3 (EGR1, EGR3), and cytokines/chemokines (IL5, IL6, IL13, CCL11), which have all been implicated in the onset of fibrosis. The changes in our selected genes of interest did not all start at the same time point. The transcriptome microarray data, validated by quantitative Real-Time PCR, was also confirmed by immunoblotting and customized Enzyme Linked Immunosorbent Assays (ELISA) array showing significant increases in the protein expression levels of fibrogenic EGR1, SNAI1 and IL 6. Furthermore, phosphorylated SMAD2/3 which induces a fibrogenic phenotype is also upregulated accompanied by an increased nuclear translocation of JunB. Pathway analysis of the validated genes and phospho-proteins regulated by the parasite provides the very early fibrotic interactome operating when T. cruzi comes in contact with PHCM. The interactome architecture shows that the parasite induces both TGF-beta dependent and independent fibrotic pathways, providing an early molecular foundation for Chagasic cardiomyopathy. Examining the very early molecular events of T. cruzi cellular infection may provide disease biomarkers which will aid clinicians in patient assessment and identification of patient subpopulation at risk of developing Chagasic cardiomyopathy.
C1 [Udoko, Aniekanabassi N.; Dykan, Andrey; Rachakonda, Girish; Villalta, Fernando; Mandape, Sammed N.; Lima, Maria F.; Pratap, Siddharth; Nde, Pius N.] Meharry Med Coll, Dept Microbiol & Immunol, Nashville, TN 37208 USA.
[Johnson, Candice A.] Food & Drug Adm, Silver Spring, MD USA.
[Lima, Maria F.; Pratap, Siddharth] Meharry Med Coll, Bioinformat & Mol Biol Core, Sch Grad Studies & Res, Nashville, TN 37208 USA.
RP Nde, PN (reprint author), Meharry Med Coll, Dept Microbiol & Immunol, Nashville, TN 37208 USA.
EM pnde@mmc.edu
FU National Institutes of Health from National Institute of Minority Health
and Health Disparities (NIMHD) [U54 MD007593, G12 MD007586]; National
Institute of Allergy and Infectious Diseases (NIAID) [AI007281,
AI083925, AI080580]; National Heart, Lung, and Blood Institute (NHLBI)
[HL007737]; National Institute of General Medical Sciences (NIGMS)
[GM059994]
FX This work was supported by the National Institutes of Health grants #
U54 MD007593 (PNN, ANU, SNM, SP), G12 MD007586 (MFL, SP) from the
National Institute of Minority Health and Health Disparities (NIMHD);
AI007281 (FV, CAJ), AI083925 (PNN) and AI080580 (FV, CAJ) from the
National Institute of Allergy and Infectious Diseases (NIAID); HL007737
(FV, CAJ) from National Heart, Lung, and Blood Institute (NHLBI);
GM059994 (MFL, CAJ) from the National Institute of General Medical
Sciences (NIGMS). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 72
TC 0
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U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD JAN
PY 2016
VL 10
IS 1
AR e0003747
DI 10.1371/journal.pntd.0003747
PG 23
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DH1SR
UT WOS:000372565700001
PM 26771187
ER
PT J
AU Dadhania, V
Muskhelishvili, L
Latendresse, J
Mehendale, H
AF Dadhania, V.
Muskhelishvili, L.
Latendresse, J.
Mehendale, H.
TI Hepatic Overexpression of Annexin A1 and A2 Underlies the
Heteroprotection by Thioacetamide Against a Lethal Dose of Acetaminophen
in Mice
SO INTERNATIONAL JOURNAL OF TOXICOLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-College-of-Toxicology (ACT)
CY NOV 08-11, 2015
CL Summerlin, NV
SP Amer Coll Toxicol
C1 [Dadhania, V.; Mehendale, H.] Univ Louisiana Monroe, Dept Toxicol, Monroe, LA USA.
[Muskhelishvili, L.; Latendresse, J.] Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1091-5818
EI 1092-874X
J9 INT J TOXICOL
JI Int. J. Toxicol.
PD JAN-FEB
PY 2016
VL 35
IS 1
SI SI
MA STP106
BP 53
EP 53
PG 1
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA DG7XW
UT WOS:000372298000011
ER
PT J
AU Mattes, W
AF Mattes, W.
TI Investigating Concordance of Nonclinical and Clinical Toxicity Through
Integrated Analysis
SO INTERNATIONAL JOURNAL OF TOXICOLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-College-of-Toxicology (ACT)
CY NOV 08-11, 2015
CL Summerlin, NV
SP Amer Coll Toxicol
C1 [Mattes, W.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1091-5818
EI 1092-874X
J9 INT J TOXICOL
JI Int. J. Toxicol.
PD JAN-FEB
PY 2016
VL 35
IS 1
SI SI
MA P515
BP 78
EP 79
PG 2
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA DG7XW
UT WOS:000372298000086
ER
PT J
AU Gonzalez, CM
Semple, K
Austin, J
Howard, KE
AF Gonzalez, C. M.
Semple, K.
Austin, J.
Howard, K. E.
TI Assessment of Safety and Efficacy of Ofatumumab in Human Immune System
Mice
SO INTERNATIONAL JOURNAL OF TOXICOLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-College-of-Toxicology (ACT)
CY NOV 08-11, 2015
CL Summerlin, NV
SP Amer Coll Toxicol
C1 [Gonzalez, C. M.; Semple, K.; Austin, J.; Howard, K. E.] US FDA, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1091-5818
EI 1092-874X
J9 INT J TOXICOL
JI Int. J. Toxicol.
PD JAN-FEB
PY 2016
VL 35
IS 1
SI SI
MA P518
BP 79
EP 80
PG 2
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA DG7XW
UT WOS:000372298000089
ER
PT J
AU Wang, Y
Gong, B
Liu, Z
Bisgin, H
Tong, W
AF Wang, Y.
Gong, B.
Liu, Z.
Bisgin, H.
Tong, W.
TI An Integrated Analysis of Genomic and miroRNAExpression Profiles to
Characterize the Specific Toxicological Signatures for Drugs with
Similar Chemical Structure
SO INTERNATIONAL JOURNAL OF TOXICOLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-College-of-Toxicology (ACT)
CY NOV 08-11, 2015
CL Summerlin, NV
SP Amer Coll Toxicol
C1 [Wang, Y.; Gong, B.; Liu, Z.; Bisgin, H.; Tong, W.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RI Gong, Binsheng/E-2306-2015
OI Gong, Binsheng/0000-0002-8724-5435
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1091-5818
EI 1092-874X
J9 INT J TOXICOL
JI Int. J. Toxicol.
PD JAN-FEB
PY 2016
VL 35
IS 1
SI SI
MA P524
BP 82
EP 82
PG 1
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA DG7XW
UT WOS:000372298000095
ER
PT J
AU Daley, MF
Goddard, K
McClung, M
Davidson, A
Weiss, G
Palen, T
Nyirenda, C
Platt, R
Courtney, B
Reichman, ME
AF Daley, Matthew F.
Goddard, Kristin
McClung, Melissa
Davidson, Arthur
Weiss, Gretchen
Palen, Ted
Nyirenda, Carsie
Platt, Richard
Courtney, Brooke
Reichman, Marsha E.
TI Using a Handheld Device for Patient Data Collection: A Pilot for Medical
Countermeasures Surveillance
SO PUBLIC HEALTH REPORTS
LA English
DT Article
ID PROGRAM; FOOD
AB Medical countermeasures (MCMs) are medical products used during public health emergencies. This study, conducted within the Mini-Sentinel Initiative, sought to develop the patient identification and matching processes necessary to assess safety outcomes for MCMs. A handheld device was used to collect identifying information (e.g., name, birthdate, and sex) from the driver's licenses of 421 individuals presenting for routine care at their primary care medical office. Overall, 374 individuals (88.8%) could be linked to their electronic health data using driver's license information. The device was also pilot-tested at a seasonal influenza immunization clinic: detailed vaccine information (e.g., lot number and manufacturer) was captured with a high degree of accuracy. This investigation demonstrated that a handheld device is a feasible means of collecting patient identity and medical product receipt data. This capacity should be useful for safety surveillance of MCMs, particularly when dispensed in settings outside the traditional health-care delivery system.
C1 [Daley, Matthew F.; Goddard, Kristin; Palen, Ted; Nyirenda, Carsie] Kaiser Permanente Colorado, Inst Hlth Res, 10065 E Harvard Ave 300, Denver, CO 80231 USA.
[Daley, Matthew F.] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA.
[McClung, Melissa; Davidson, Arthur] Denver Publ Hlth, Denver, CO USA.
[Weiss, Gretchen] Natl Assoc Cty & City Hlth Officials, Washington, DC USA.
[Platt, Richard] Harvard Univ, Sch Med, Boston, MA USA.
[Platt, Richard] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA.
[Courtney, Brooke] US FDA, Off Counterterrorism & Emerging Threats, Off Commissioner, Silver Spring, MD USA.
[Reichman, Marsha E.] US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD USA.
RP Daley, MF (reprint author), Kaiser Permanente Colorado, Inst Hlth Res, 10065 E Harvard Ave 300, Denver, CO 80231 USA.
EM matthew.f.daley@kp.org
FU Mini-Sentinel project - U.S. Food and Drug Administration (FDA) through
the U.S. Department of Health and Human Services [HHSF22301007T,
HHSF223200910006I]
FX This study was supported under Task Order 7 (contract #HHSF22301007T) of
the Mini-Sentinel project (contract #HHSF223200910006I), which was
funded by the U.S. Food and Drug Administration (FDA) through the U.S.
Department of Health and Human Services. Colleagues from the FDA were
involved in the conceptualization, design, analysis, and interpretation
of the findings from this pilot project.
NR 7
TC 0
Z9 0
U1 1
U2 1
PU ASSOC SCHOOLS PUBLIC HEALTH
PI WASHINGTON
PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA
SN 0033-3549
J9 PUBLIC HEALTH REP
JI Public Health Rep.
PD JAN-FEB
PY 2016
VL 131
IS 1
BP 30
EP 34
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DG9HD
UT WOS:000372392500008
PM 26843667
ER
PT J
AU Chavez, BK
Agarabi, CD
Read, EK
Boyne, MT
Khan, MA
Brorson, KA
AF Chavez, Brittany K.
Agarabi, Cyrus D.
Read, Erik K.
Boyne, Michael T., II
Khan, Mansoor A.
Brorson, Kurt A.
TI Improved Stability of a Model IgG3 by DoE-Based Evaluation of Buffer
Formulations
SO BIOMED RESEARCH INTERNATIONAL
LA English
DT Article
ID MAMMALIAN-CELL CULTURE; MONOCLONAL-ANTIBODY; THERAPEUTICS; PERSPECTIVE;
BIOREACTORS; PARTICLES; QUALITY; DESIGN; PH
AB Formulating appropriate storage conditions for biopharmaceutical proteins is essential for ensuring their stability and thereby their purity, potency, and safety over their shelf-life. Using a model murine IgG3 produced in a bioreactor system, multiple formulation compositions were systematically explored in a DoE design to optimize the stability of a challenging antibody formulation worst case. The stability of the antibody in each buffer formulation was assessed by UV/VIS absorbance at 280 nm and 410 nm and size exclusion high performance liquid chromatography (SEC) to determine overall solubility, opalescence, and aggregate formation, respectively. Upon preliminary testing, acetate was eliminated as a potential storage buffer due to significant visible precipitate formation. An additional 2(4) full factorial DoE was performed that combined the stabilizing effect of arginine with the buffering capacity of histidine. From this final DoE, an optimized formulation of 200 mM arginine, 50 mM histidine, and 100 mM NaCl at a pH of 6.5 was identified to substantially improve stability under long-term storage conditions and after multiple freeze/thaw cycles. Thus, our data highlights the power of DoE based formulation screening approaches even for challenging monoclonal antibody molecules.
C1 [Chavez, Brittany K.; Read, Erik K.; Brorson, Kurt A.] US FDA, Div 2, Off Biotechnol Prod, OPQ,CDER, Silver Spring, MD 20903 USA.
[Agarabi, Cyrus D.; Khan, Mansoor A.] US FDA, Div Prod Qual Res, Off Testing & Res, OPQ,CDER, Silver Spring, MD 20903 USA.
[Boyne, Michael T., II] US FDA, Div Pharmaceut Anal, Off Testing & Res, OPQ,CDER, Silver Spring, MD 20903 USA.
RP Brorson, KA (reprint author), US FDA, Div 2, Off Biotechnol Prod, OPQ,CDER, Silver Spring, MD 20903 USA.
EM kurt.brorson@fda.hhs.gov
FU CDER's Critical Path Initiative [1500]
FX The authors acknowledge CDER's Critical Path Initiative, Grant no. 1500,
for support of this project. This project was supported in part by an
appointment to the Research Participation Program at the CDER/Office of
Biotechnology Products, US Food and Drug Administration, administered by
the Oak Ridge Institute for Science and Education through an interagency
agreement between the US Department of Energy and FDA. The authors would
also like to acknowledge Juhong Liu and Audrey Jia for their careful
comments in the preparation of this paper.
NR 22
TC 2
Z9 2
U1 4
U2 8
PU HINDAWI PUBLISHING CORP
PI NEW YORK
PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA
SN 2314-6133
EI 2314-6141
J9 BIOMED RES INT
JI Biomed Res. Int.
PY 2016
AR 2074149
DI 10.1155/2016/2074149
PG 8
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA DG6SZ
UT WOS:000372217700001
ER
PT J
AU Papafragkou, E
Kulka, M
AF Papafragkou, Efstathia
Kulka, Michael
TI Review: Approaches to the Viral Extraction, Detection, and
Identification of Hepatitis Viruses, HAV and HEV, in Foods
SO JOURNAL OF AOAC INTERNATIONAL
LA English
DT Review
ID DNA MICROARRAY TECHNOLOGY; POLYMERASE CHAIN-REACTION; HUMAN ENTERIC
VIRUSES; NORWALK-LIKE VIRUSES; TIME RT-PCR; A-VIRUS; CELL-CULTURE; FRESH
PRODUCE; INFECTIOUS-HEPATITIS; POLYETHYLENE-GLYCOL
AB Although the incidence rate of hepatitis A virus (HAV) infection has been on the decline in developed countries, in part due to immunization availability, high profile outbreaks continue to be reported. Hepatitis E virus has been recognized as an emerging pathogen in industrialized countries. While associated with waterborne illnesses, particularly in undeveloped countries, several animal species have been identified as reservoirs for the virus. Consequently, the potential of zoonotic transmission exists as a function of the consumption of infected animals. In this review we provide a comparative overview of these two virus species with regard to their known virus properties, discuss extraction methodologies, and describe some basic principles and methodology applied toward the isolation of these viruses (as particles or their isolated genomes) from food commodities. We also discuss the challenges that remain as experimental hurdles to extraction of such viruses from food. As HAV has been the most extensively studied with regard to virus detection in foods, it often serves as a model virus for current and future development of sample preparation methodology for foodborne virus detection. Lastly, we discuss the application and role of current and developing technologies in the post-extraction detection and identification of these viruses from foods.
C1 [Papafragkou, Efstathia; Kulka, Michael] US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Mol Biol, Mod 1 Bldg,HFS-025 Muirkirk Rd, Laurel, MD 20708 USA.
RP Kulka, M (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Mol Biol, Mod 1 Bldg,HFS-025 Muirkirk Rd, Laurel, MD 20708 USA.
EM michael.kulka@fda.hhs.gov
NR 125
TC 1
Z9 1
U1 10
U2 16
PU AOAC INT
PI GAITHERSBURG
PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA
SN 1060-3271
EI 1944-7922
J9 J AOAC INT
JI J. AOAC Int.
PD JAN-FEB
PY 2016
VL 99
IS 1
BP 130
EP 142
DI 10.5740/jaoacint.15-0164
PG 13
WC Chemistry, Analytical; Food Science & Technology
SC Chemistry; Food Science & Technology
GA DG3EX
UT WOS:000371953400017
PM 26846628
ER
PT J
AU Vega, VA
Young, M
Todd, S
AF Vega, Victor A.
Young, Michelle
Todd, Sarah
TI Laboratory Information Bulletin: Quantitation of Aflatoxin M-1 in Bovine
Milk by Liquid Chromatography with Fluorescence Detection
SO JOURNAL OF AOAC INTERNATIONAL
LA English
DT Article
AB An extraction for aflatoxin M-1 from bovine milk samples is described. The samples were extracted by adding 10 mL acetonitrile to 10 g of sample. The extract was salted out with sodium chloride and magnesium sulfate to separate the water and acetonitrile. The organic layer was dried down and reconstituted in water before being subjected to an immunoaffinity column for cleanup. Once the analyte was isolated, quantitation was obtained by LC with fluorescence detection. LC/fluorescence parameters were optimized with an Agilent Poroshell 120 C18 LC column resulting in a 4 min run time. To test the procedure's robustness, three different kinds of matrixes were fortified at three different levels each. Whole milk, reduced fat milk, and skim milk samples were fortified at approximately 0.25, 0.5, and 1.0 mu g/kg. Recoveries from all samples ranged from 70 to 100%. Confirmation was accomplished by injecting the samples in an ion trap mass spectrometer. The method presented here entails an extraction step followed by an immunoaffinity column clean-up that leads to fast analysis time and consistent recoveries with an uncertainty measurement of 10.5% and method detection limit of less than 0.011 mu g/kg.
C1 [Vega, Victor A.; Young, Michelle; Todd, Sarah] US FDA, Southeast Reg Lab, 60 8th St NE, Atlanta, GA 30309 USA.
RP Vega, VA (reprint author), US FDA, Southeast Reg Lab, 60 8th St NE, Atlanta, GA 30309 USA.
EM victor.vega@fda.hhs.gov
NR 5
TC 0
Z9 0
U1 0
U2 1
PU AOAC INT
PI GAITHERSBURG
PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA
SN 1060-3271
EI 1944-7922
J9 J AOAC INT
JI J. AOAC Int.
PD JAN-FEB
PY 2016
VL 99
IS 1
BP 174
EP 179
DI 10.5740/jaoacint.15-0177
PG 6
WC Chemistry, Analytical; Food Science & Technology
SC Chemistry; Food Science & Technology
GA DG3EX
UT WOS:000371953400021
PM 26822405
ER
PT J
AU Restrepo, BJ
Rieger, M
AF Restrepo, Brandon J.
Rieger, Matthias
TI Trans fat and cardiovascular disease mortality: Evidence from bans in
restaurants in New York
SO JOURNAL OF HEALTH ECONOMICS
LA English
DT Article
DE Trans fat; Restaurant; Ban; Cardiovascular disease; Mortality
ID CORONARY-HEART-DISEASE; ACIDS; CHOLESTEROL; RISK; DIET; INFLAMMATION;
PROGRESS; MARKERS; ADULTS; DEATH
AB This paper analyzes the impact of trans fat bans on cardiovascular disease (CVD) mortality rates. Several New York State jurisdictions have restricted the use of ingredients containing artificial trans fat in food service establishments. The resulting within-county variation over time and the differential timing of the policy's rollout is used in estimation. The results indicate that the policy caused a 4.5% reduction in CVD mortality rates, or 13 fewer CVD deaths per 100,000 persons per year. The averted deaths can be valued at about $3.9 million per 100,000 persons annually. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Restrepo, Brandon J.] US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
[Rieger, Matthias] Erasmus Univ, Int Inst Social Studies ISS, Kortenaerkade 12, NL-2518 AX The Hague, Netherlands.
RP Rieger, M (reprint author), Erasmus Univ, Int Inst Social Studies ISS, Kortenaerkade 12, NL-2518 AX The Hague, Netherlands.
EM brandon.restrepo@fda.hhs.gov; rieger@iss.nl
OI Restrepo, Brandon/0000-0002-8005-4839
NR 40
TC 3
Z9 3
U1 1
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-6296
EI 1879-1646
J9 J HEALTH ECON
JI J. Health Econ.
PD JAN
PY 2016
VL 45
BP 176
EP 196
DI 10.1016/j.jhealeco.2015.09.005
PG 21
WC Economics; Health Care Sciences & Services; Health Policy & Services
SC Business & Economics; Health Care Sciences & Services
GA DG1PU
UT WOS:000371840800014
PM 26620830
ER
PT J
AU Zhang, G
Guo, DW
Dash, PK
Arainga, M
Wiederin, JL
Haverland, NA
Knibbe-Hollinger, J
Martinez-Skinner, A
Ciborowski, P
Goodfellow, VS
Wysocki, TA
Wysocki, BJ
Poluektova, LY
Liu, XM
McMillan, JM
Gorantla, S
Gelbard, HA
Gendelman, HE
AF Zhang, Gang
Guo, Dongwei
Dash, Prasanta K.
Arainga, Mariluz
Wiederin, Jayme L.
Haverland, Nicole A.
Knibbe-Hollinger, Jaclyn
Martinez-Skinner, Andrea
Ciborowski, Pawel
Goodfellow, Val S.
Wysocki, Tadeusz A.
Wysocki, Beata J.
Poluektova, Larisa Y.
Liu, Xin-Ming
McMillan, JoEllyn M.
Gorantla, Santhi
Gelbard, Harris A.
Gendelman, Howard E.
TI The mixed lineage kinase-3 inhibitor URMC-099 improves therapeutic
outcomes for long-acting antiretroviral therapy'
SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
LA English
DT Article
DE HIV-1; Long-acting nanoformulations; URMC-099; Humanized mice;
Phagolysosome; Rab proteins
ID HUMAN-IMMUNODEFICIENCY-VIRUS; MONOCYTE-DERIVED MACROPHAGE; HIV-1
INFECTION; P-GLYCOPROTEIN; HUMANIZED MICE; DRUG-DELIVERY; ACTIVATION;
ATAZANAVIR; ENDOSOMES; COMPARTMENTS
AB During studies to extend the half-life of crystalline nanoformulated antiretroviral therapy (nanoART) the mixed lineage kinase-3 inhibitor URMC-099, developed as an adjunctive neuroprotective agent was shown to facilitate antiviral responses. Long-acting ritonavir-boosted atazanavir (nanoATV/r) nanoformulations co-administered with URMC-099 reduced viral load and the numbers of HIV-1 infected CD4+ T-cells in lymphoid tissues more than either drug alone in infected humanized NOD/SCID/IL2R gamma c-/- mice. The drug effects were associated with sustained ART depots. Proteomics analyses demonstrated that the antiretroviral responses were linked to affected phagolysosomal storage pathways leading to sequestration of nanoATV/r in Rab-associated recycling and late endosomes; sites associated with viral maturation. URMC-099 administered with nanoATV induced a dose-dependent reduction in HIV-1p24 and reverse transcriptase activity. This drug combination offers a unique chemical marriage for cell-based viral clearance.
From the Clinical Editor: Although successful in combating HIV-1 infection, the next improvement in antiretroviral therapy (nanoART) would be to devise long acting therapy, such as intra-cellular depots. In this report, the authors described the use of nanoformulated antiretroviral therapy given together with the mixed lineage kinase-3 inhibitor URMC-099, and showed that this combination not only prolonged drug half-life, but also had better efficacy. The findings are hoped to be translated into the clinical setting in the future. (C) 2015 The Authors. Published by Elsevier Inc.
C1 [Zhang, Gang; Guo, Dongwei; Dash, Prasanta K.; Arainga, Mariluz; Wiederin, Jayme L.; Haverland, Nicole A.; Knibbe-Hollinger, Jaclyn; Martinez-Skinner, Andrea; Ciborowski, Pawel; Poluektova, Larisa Y.; Liu, Xin-Ming; McMillan, JoEllyn M.; Gorantla, Santhi; Gendelman, Howard E.] Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE USA.
[Guo, Dongwei; Liu, Xin-Ming; Gendelman, Howard E.] Univ Nebraska Med Ctr, Dept Pharmaceut Sci, Omaha, NE USA.
[Wiederin, Jayme L.] Univ Nebraska Med Ctr, Off Vice Chancellor Res, Omaha, NE USA.
[Goodfellow, Val S.] Califia Bio, San Diego, CA USA.
[Wysocki, Tadeusz A.; Wysocki, Beata J.] Univ Nebraska Lincoln, Dept Comp & Elect Engn, Omaha, NE USA.
[Gelbard, Harris A.] Univ Rochester, Med Ctr, Sch Med & Dent, Dept Neurol,Ctr Neural Dev & Dis, Rochester, NY 14642 USA.
[Haverland, Nicole A.] Northwestern Univ, Dept Chem, 2145 Sheridan Rd, Evanston, IL 60208 USA.
[Liu, Xin-Ming] US FDA, Silver Spring, MD 20993 USA.
RP Gendelman, HE (reprint author), Dept Pharmacol & Expt Neurosci, 985880 Nebraska Med Ctr, Omaha, NE USA.
EM hegendel@unmc.edu
FU University of Nebraska Foundation; UNMC Vice Chancellor's office;
National Institutes of Health [P01 MH64570, RO1 MH104147, P30 AI078494,
P01 DA028555, R01 NS36126, P01 NS31492, 2R01 NS034239, P01 NS43985, P30
MH062261, R01 AG043540]
FX This work was supported by the University of Nebraska Foundation which
includes individual donations from Dr. Carol Swarts and Frances and
Louie Blumkin, the UNMC Vice Chancellor's office and National Institutes
of Health grants P01 MH64570, RO1 MH104147 and P30 AI078494 (to H.A.G.)
and P01 DA028555, R01 NS36126, P01 NS31492, 2R01 NS034239, P01 NS43985,
P30 MH062261 and R01 AG043540 (to H.E.G.). The funders have had no role
in study design.
NR 64
TC 4
Z9 4
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1549-9634
EI 1549-9642
J9 NANOMED-NANOTECHNOL
JI Nanomed.-Nanotechnol. Biol. Med.
PD JAN
PY 2016
VL 12
IS 1
BP 109
EP 122
DI 10.1016/j.nano.2015.09.009
PG 14
WC Nanoscience & Nanotechnology; Medicine, Research & Experimental
SC Science & Technology - Other Topics; Research & Experimental Medicine
GA DG1BR
UT WOS:000371800600011
PM 26472049
ER
PT J
AU Navin, CV
Krishna, KS
Theegala, CS
Kumar, CSSR
AF Navin, Chelliah V.
Krishna, Katla Sai
Theegala, Chandra S.
Kumar, Challa S. S. R.
TI Space and time-resolved probing of heterogeneous catalysis reactions
using lab-on-a-chip
SO NANOSCALE
LA English
DT Article
ID 2,5-FURANDICARBOXYLIC ACID; AEROBIC OXIDATION; SELECTIVE OXIDATION; FLOW
MICROREACTOR; RESIDENCE-TIME; REACTOR; NANOPARTICLES; NANOCLUSTERS;
BIOMASS; CHEMICALS
AB Probing catalytic reactions on a catalyst surface in real time is a major challenge. Herein, we demonstrate the utility of a continuous flow millifluidic chip reactor coated with a nanostructured gold catalyst as an effective platform for in situ investigation of the kinetics of catalytic reactions by taking 5-(hydroxymethyl) furfural (HMF) to 2,5-furandicarboxylic acid (FDCA) conversion as a model reaction. The idea conceptualized in this paper can not only dramatically change the ability to probe the time-resolved kinetics of heterogeneous catalysis reactions but also used for investigating other chemical and biological catalytic processes, thereby making this a broad platform for probing reactions as they occur within continuous flow reactors.
C1 [Navin, Chelliah V.; Krishna, Katla Sai; Kumar, Challa S. S. R.] Louisiana State Univ, CAMD, Baton Rouge, LA 70806 USA.
[Navin, Chelliah V.; Theegala, Chandra S.] Louisiana State Univ, Dept Biol & Agr Engn, Baton Rouge, LA 70803 USA.
[Navin, Chelliah V.; Theegala, Chandra S.] LSU AgCtr, Baton Rouge, LA 70803 USA.
[Navin, Chelliah V.] Louisiana State Univ, Engn Sci, Baton Rouge, LA 70803 USA.
[Navin, Chelliah V.; Krishna, Katla Sai; Kumar, Challa S. S. R.] Louisiana State Univ, Cain Dept Chem Engn, Ctr Atom Level Catalyst Design, Baton Rouge, LA 70803 USA.
[Navin, Chelliah V.] US Food & Drug Adm FDA, Div Pharmaceut Anal, 645 S Newstead Ave, St Louis, MO 63110 USA.
[Krishna, Katla Sai] Univ Texas El Paso, Dept Chem, El Paso, TX 79902 USA.
[Kumar, Challa S. S. R.] Rowland Inst Harvard, 100 Edwin H Land Blvd, Cambridge, MA 02142 USA.
RP Kumar, CSSR (reprint author), Louisiana State Univ, CAMD, Baton Rouge, LA 70806 USA.; Kumar, CSSR (reprint author), Louisiana State Univ, Cain Dept Chem Engn, Ctr Atom Level Catalyst Design, Baton Rouge, LA 70803 USA.; Kumar, CSSR (reprint author), Rowland Inst Harvard, 100 Edwin H Land Blvd, Cambridge, MA 02142 USA.
EM challa@fas.harvard.edu
FU Center for Atomic Level Catalyst Design, an Energy Frontier Research
Center - U.S. Department of Energy, Office of Science, Office of Basic
Energy Sciences [DE-SC0001058]; [LEQSF (2009-14)-EFRC-MATCH];
[LEDSF-EPS(2012)-OPT-IN-15]
FX This research work is supported as part of the Center for Atomic Level
Catalyst Design, an Energy Frontier Research Center funded by the U.S.
Department of Energy, Office of Science, Office of Basic Energy Sciences
under Award Number DE-SC0001058 and also supported by the Board of
Regents under grants award number LEQSF (2009-14)-EFRC-MATCH and
LEDSF-EPS(2012)-OPT-IN-15.
NR 35
TC 0
Z9 0
U1 12
U2 28
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 2040-3364
EI 2040-3372
J9 NANOSCALE
JI Nanoscale
PY 2016
VL 8
IS 10
BP 5546
EP 5551
DI 10.1039/c5nr06752a
PG 6
WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials
Science, Multidisciplinary; Physics, Applied
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA DF9FC
UT WOS:000371665400018
PM 26888331
ER
PT S
AU Stam, C
Behar, A
Cooper, M
AF Stam, Christina
Behar, Alberto
Cooper, Moogega
BE Micic, M
TI Sampling of Microbiological Samples
SO SAMPLE PREPARATION TECHNIQUES FOR SOIL, PLANT, AND ANIMAL SAMPLES
SE Springer Protocols Handbooks
LA English
DT Article; Book Chapter
DE Air; Aseptic; Contamination; Filtration; Feeds; HVB; RODAC; Surfaces;
Swabs; Vacuum-sampling; Water; Wipes
ID DRY DOG FOOD; UNITED-STATES; ENVIRONMENTAL SURFACES; NONPOROUS SURFACES;
BACILLUS SPORES; COLLECTION; INFECTIONS; RECOVERY; CANADA; SWABS
AB Sampling of microorganisms from the environment presents a unique set of challenges. The various matrices in which microorganisms can survive and persist, along with the diversity in the communities that make up these environments are complex. Several types of methods exist for the detection and isolation of microbes from the environment. These methods include a variety of surface and air sampling techniques, as well as additional methodology specific to water and food samples.
C1 [Stam, Christina; Behar, Alberto] US FDA, 6502 S Archer Rd, Bedford Pk, IL 60501 USA.
[Stam, Christina; Behar, Alberto] CALTECH, Jet Prop Lab, 4800 Oak Grove Dr, Pasadena, CA 91101 USA.
[Cooper, Moogega] CALTECH, Jet Prop Lab, Biotechnol & Planetary Protect Grp, 4800 Oak Grove Dr, Pasadena, CA 91101 USA.
RP Cooper, M (reprint author), CALTECH, Jet Prop Lab, Biotechnol & Planetary Protect Grp, 4800 Oak Grove Dr, Pasadena, CA 91101 USA.
EM Christina.stam@fda.hhs.gov; alberto.behar@jpl.nasa.gov;
moogega.cooper@jpl.nasa.gov
NR 35
TC 0
Z9 0
U1 2
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES
SN 1949-2448
BN 978-1-4939-3185-9; 978-1-4939-3184-2
J9 SPRINGER PROTOC HAND
PY 2016
BP 25
EP 39
DI 10.1007/978-1-4939-3185-9_3
D2 10.1007/978-1-4939-3185-9
PG 15
WC Plant Sciences
SC Plant Sciences
GA BE4EL
UT WOS:000371627100005
ER
PT S
AU Binet, R
Tatavarthy, A
AF Binet, Rachel
Tatavarthy, Aparna
BE Micic, M
TI Sample Preparation for Multiplex PCR Assays for Food and Agriculture
Applications
SO SAMPLE PREPARATION TECHNIQUES FOR SOIL, PLANT, AND ANIMAL SAMPLES
SE Springer Protocols Handbooks
LA English
DT Article; Book Chapter
DE Foodborne; PCR; Multiplex; Inhibitors; Sample preparation; Sensitivity;
Detection
ID ESCHERICHIA-COLI O157H7; REAL-TIME PCR; UNITED-STATES; IMMUNOMAGNETIC
SEPARATION; LISTERIA-MONOCYTOGENES; SALMONELLA CELLS; IRRIGATION WATER;
BORNE PATHOGENS; RAPID DETECTION; QUANTIFICATION
AB Foodborne pathogens and spoilage microorganisms influence the safety and quality of food. Polymerase chain reaction (PCR)-based technologies in food diagnostics have become a promising alternative to conventional culturing approaches due to their rapidity, excellent analytical sensitivity and selectivity, and potential for quantification. Although molecular approaches can be extremely effective with pure microbial cultures, the sensitivity can be reduced radically when they are applied directly to food samples, owing to the complexity of the matrix and the presence of PCR-inhibitory components. In addition, the contamination level of microbial pathogens in food samples is usually very low, making their detection a challenge. In this book chapter, we are presenting various methods that are used to facilitate PCR detection from food samples, including optimization of the DNA amplification conditions by the use of amplification facilitators and sample preparation methods that will either separate the microbial cells from the PCR inhibitors and/or concentrate the microbial cells to detectable concentrations.
C1 [Binet, Rachel; Tatavarthy, Aparna] US FDA, Div Microbiol HFS711, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
RP Binet, R (reprint author), US FDA, Div Microbiol HFS711, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM rachel.binet@fda.hhs.gov; aparna.tatavarthy@fda.hhs.gov
NR 38
TC 0
Z9 0
U1 3
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES
SN 1949-2448
BN 978-1-4939-3185-9; 978-1-4939-3184-2
J9 SPRINGER PROTOC HAND
PY 2016
BP 139
EP 151
DI 10.1007/978-1-4939-3185-9_11
D2 10.1007/978-1-4939-3185-9
PG 13
WC Plant Sciences
SC Plant Sciences
GA BE4EL
UT WOS:000371627100013
ER
PT S
AU Kase, JA
Pfefer, TL
AF Kase, Julie Ann
Pfefer, Tina Lusk
BE Micic, M
TI Nucleic Acid Sample Preparation from Dairy Products and Milk
SO SAMPLE PREPARATION TECHNIQUES FOR SOIL, PLANT, AND ANIMAL SAMPLES
SE Springer Protocols Handbooks
LA English
DT Article; Book Chapter
DE Nucleic acid; Extraction; Milk; Cheese; Dairy; DNA; RNA; Cell lysis;
Fat; Kits
ID POLYMERASE-CHAIN-REACTION; BACILLUS-ANTHRACIS SPORES; DNA EXTRACTION
METHODS; LISTERIA-MONOCYTOGENES; FOOD SAMPLES; RAW-MILK;
STAPHYLOCOCCUS-AUREUS; PCR DETECTION; GENOMIC DNA; CHEESE
AB The isolation of RNA and DNA of sufficient quantity, of an optimal intact length (quality), and without contaminants (purity) is important for a range of research initiatives including pathogen detection during an outbreak and the study of the background microflora in dairy products. Nucleic acid isolation is a multistep procedure that may begin with the separation of cells from the matrix, followed by cell lysis, then nucleic acid extraction and recovery. Herein we compare and evaluate published methods used to extract nucleic acids from various dairy matrices. Specific topics include removal of matrix components by centrifugation, organic solvents, and Proteinase K treatment along with cell lysis accomplished by enzymatic (e.g., lysozyme), physical (e.g., freeze/thawing, boiling, bead-beating), and chemical (e.g., detergent) means. Also mentioned is the recent use of automated nucleic acid extraction procedures.
C1 [Kase, Julie Ann; Pfefer, Tina Lusk] US FDA, Div Microbiol, Off Regulatory Sci, 5100 Paint Branch Pkwy,HFS 711, College Pk, MD 20740 USA.
RP Pfefer, TL (reprint author), US FDA, Div Microbiol, Off Regulatory Sci, 5100 Paint Branch Pkwy,HFS 711, College Pk, MD 20740 USA.
EM tina.pfefer@fda.hhs.gov
NR 43
TC 0
Z9 0
U1 2
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES
SN 1949-2448
BN 978-1-4939-3185-9; 978-1-4939-3184-2
J9 SPRINGER PROTOC HAND
PY 2016
BP 231
EP 244
DI 10.1007/978-1-4939-3185-9_16
D2 10.1007/978-1-4939-3185-9
PG 14
WC Plant Sciences
SC Plant Sciences
GA BE4EL
UT WOS:000371627100018
ER
PT S
AU Cooper, M
Stam, C
AF Cooper, Moogega
Stam, Christina
BE Micic, M
TI Nucleic Acid Purification from Soil and Environmental Sources
SO SAMPLE PREPARATION TECHNIQUES FOR SOIL, PLANT, AND ANIMAL SAMPLES
SE Springer Protocols Handbooks
LA English
DT Article; Book Chapter
DE DNA; Soil; Purification
ID RIBOSOMAL-RNA; MICROBIAL DIVERSITY; DIRECT EXTRACTION; DNA EXTRACTION;
BACTERIAL-DNA; HUMIC ACIDS; PCR; SAMPLES; MICROORGANISMS; SEDIMENTS
AB The extraction of nucleic acids from soil and environmental samples allows scientists the opportunity to discern the microbial community irrespective of viability and cultivability. General nucleic acid extraction and purification approaches are discussed as well as their limitations. Soil type and humic acid content are among many factors that can affect the processing approach. The environmental sample collection, extraction, and purification protocol developed for a low-population density cleanroom environment is discussed as a specific example of environmental sample processing. This practical application of DNA purification techniques were used to assess microbial diversity and abundance in spacecraft assembly cleanrooms.
C1 [Cooper, Moogega] CALTECH, Jet Prop Lab, Biotechnol & Planetary Protect Grp, 4800 Oak Grove Dr, Pasadena, CA 91101 USA.
[Stam, Christina] US FDA, 6502 S Archer Rd, Bedford Pk, IL 60501 USA.
RP Cooper, M (reprint author), CALTECH, Jet Prop Lab, Biotechnol & Planetary Protect Grp, 4800 Oak Grove Dr, Pasadena, CA 91101 USA.
EM moogega.cooper@jpl.nasa.gov; Christina.stam@fda.hhs.gov
NR 37
TC 0
Z9 0
U1 3
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES
SN 1949-2448
BN 978-1-4939-3185-9; 978-1-4939-3184-2
J9 SPRINGER PROTOC HAND
PY 2016
BP 307
EP 314
DI 10.1007/978-1-4939-3185-9_21
D2 10.1007/978-1-4939-3185-9
PG 8
WC Plant Sciences
SC Plant Sciences
GA BE4EL
UT WOS:000371627100023
ER
PT B
AU Lampel, KA
Wilson, G
AF Lampel, Keith A.
Wilson, George
BE Cook, N
DAgostino, M
Thompson, KC
TI Food industry current status
SO MOLECULAR MICROBIAL DIAGNOSTIC METHODS: PATHWAYS TO IMPLEMENTATION FOR
THE FOOD AND WATER INDUSTRIES
LA English
DT Article; Book Chapter
ID DNA; AMPLIFICATION; METAGENOMICS; SAMPLES; PCR
C1 [Lampel, Keith A.] US FDA, Div Mol Biol, Laurel, MD USA.
[Wilson, George] Wilson & Associates LLC, Div Mol Biol, Lutherville Timonium, MD USA.
RP Lampel, KA (reprint author), US FDA, Div Mol Biol, Laurel, MD USA.
NR 15
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND
BN 978-0-12-417170-1; 978-0-12-416999-9
PY 2016
BP 1
EP 17
DI 10.1016/B978-0-12-416999-9.00001-0
PG 17
WC Food Science & Technology; Microbiology; Water Resources
SC Food Science & Technology; Microbiology; Water Resources
GA BE3UJ
UT WOS:000371268500002
ER
PT J
AU Caucci, L
Myers, KJ
Barrett, HH
AF Caucci, Luca
Myers, Kyle J.
Barrett, Harrison H.
TI Radiance and photon noise: imaging in geometrical optics, physical
optics, quantum optics and radiology
SO OPTICAL ENGINEERING
LA English
DT Article
DE radiance; photon noise; photon processing
ID NEUMANN-SERIES APPROACH; LIST-MODE LIKELIHOOD; GAMMA-RAY DETECTORS;
OBJECTIVE ASSESSMENT; GENERALIZED RADIANCE; QUALITY; COHERENCE;
RADIOMETRY; TRANSPORT; PROPAGATION
AB The statistics of detector outputs produced by an imaging system are derived from basic radiometric concepts and definitions. We show that a fundamental way of describing a photon-limited imaging system is in terms of a Poisson random process in spatial, angular, and wavelength variables. We begin the paper by recalling the concept of radiance in geometrical optics, radiology, physical optics, and quantum optics. The propagation and conservation laws for radiance in each of these domains are reviewed. Building upon these concepts, we distinguish four categories of imaging detectors that all respond in some way to the incident radiance, including the new category of photon-processing detectors (capable of measuring radiance on a photon-by-photon basis). This allows us to rigorously show how the concept of radiance is related to the statistical properties of detector outputs and to the information content of a single detected photon. A Monte-Carlo technique, which is derived from the Boltzmann transport equation, is presented as a way to estimate probability density functions to be used in reconstruction from photon-processing data. (C) 2016 Society of Photo-Optical Instrumentation Engineers (SPIE)
C1 [Caucci, Luca; Barrett, Harrison H.] Univ Arizona, Dept Med Imaging, Ctr Gamma Ray Imaging, 1609 North Warren Ave, Tucson, AZ 85724 USA.
[Myers, Kyle J.] US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
[Barrett, Harrison H.] Univ Arizona, Coll Opt Sci, 1630 East Univ Blvd, Tucson, AZ 85719 USA.
RP Caucci, L (reprint author), Univ Arizona, Dept Med Imaging, Ctr Gamma Ray Imaging, 1609 North Warren Ave, Tucson, AZ 85724 USA.
EM caucci@email.arizona.edu
FU National Institutes of Health [R37 EB000803, P41 EB002035]
FX We have benefited significantly from discussions with Abhinav Jha and
Eric Clarkson. This research was supported by the National Institutes of
Health under grants R37 EB000803 and P41 EB002035.
NR 42
TC 0
Z9 0
U1 4
U2 6
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 0091-3286
EI 1560-2303
J9 OPT ENG
JI Opt. Eng.
PD JAN
PY 2016
VL 55
IS 1
AR 013102
DI 10.1117/1.OE.55.1.013102
PG 13
WC Optics
SC Optics
GA DF3YC
UT WOS:000371283500013
ER
PT J
AU Zeng, RP
Gavrielides, MA
Petrick, N
Sahiner, B
Li, Q
Myers, KJ
AF Zeng, Rongping
Gavrielides, Marios A.
Petrick, Nicholas
Sahiner, Berkman
Li, Qin
Myers, Kyle J.
TI Estimating local noise power spectrum from a few FBP-reconstructed CT
scans
SO MEDICAL PHYSICS
LA English
DT Article
DE local noise power spectrum; CT; FBP; detectability
ID RAY COMPUTED-TOMOGRAPHY; MODERN DIAGNOSTIC MDCT; NODULE SIZE ESTIMATION;
DETECTABILITY; COVARIANCE; IMAGES
AB Purpose: Traditional ways to estimate 2D CT noise power spectrum (NPS) involve an ensemble average of the power spectrums of many noisy scans. When only a few scans are available, regions of interest are often extracted from different locations to obtain sufficient samples to estimate the NPS. Using image samples from different locations ignores the nonstationarity of CT noise and thus cannot accurately characterize its local properties. The purpose of this work is to develop a method to estimate local NPS using only a few fan-beam CT scans.
Methods: As a result of FBP reconstruction, the CT NPS has the same radial profile shape for all projection angles, with the magnitude varying with the noise level in the raw data measurement. This allows a 2D CT NPS to be factored into products of a 1D angular and a 1D radial function in polar coordinates. The polar separability of CT NPS greatly reduces the data requirement for estimating the NPS. The authors use this property and derive a radial NPS estimation method: in brief, the radial profile shape is estimated from a traditional NPS based on image samples extracted at multiple locations. The amplitudes are estimated by fitting the traditional local NPS to the estimated radial profile shape. The estimated radial profile shape and amplitudes are then combined to form a final estimate of the local NPS. We evaluate the accuracy of the radial NPS method and compared it to traditional NPS methods in terms of normalized mean squared error (NMSE) and signal detectability index.
Results: For both simulated and real CT data sets, the local NPS estimated with no more than six scans using the radial NPS method was very close to the reference NPS, according to the metrics of NMSE and detectability index. Even with only two scans, the radial NPS method was able to achieve a fairly good accuracy. Compared to those estimated using traditional NPS methods, the accuracy improvement was substantial when a few scans were available.
Conclusions: The radial NPS method was shown to be accurate and efficient in estimating the local NPS of FBP-reconstructed 2D CT images. It presents strong advantages over traditional NPS methods when the number of scans is limited and can be extended to estimate the in-plane NPS of cone-beam CT and multislice helical CT scans.
C1 [Zeng, Rongping; Gavrielides, Marios A.; Petrick, Nicholas; Sahiner, Berkman; Li, Qin; Myers, Kyle J.] US FDA, Div Imaging Diagnost & Software Reliabil, Off Sci & Engn Labs, CDRH, Silver Spring, MD 20993 USA.
RP Zeng, RP (reprint author), US FDA, Div Imaging Diagnost & Software Reliabil, Off Sci & Engn Labs, CDRH, Silver Spring, MD 20993 USA.
EM rongping.zeng@fda.hhs.gov
NR 23
TC 2
Z9 2
U1 0
U2 0
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
EI 2473-4209
J9 MED PHYS
JI Med. Phys.
PD JAN
PY 2016
VL 43
IS 1
BP 568
EP 582
DI 10.1118/1.4939061
PG 15
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DE7XO
UT WOS:000370850600050
ER
PT J
AU Losada, L
DebRoy, C
Radune, D
Kim, M
Sanka, R
Brinkac, L
Kariyawasam, S
Shelton, D
Fratamico, PM
Kapur, V
Feng, PCH
AF Losada, Liliana
DebRoy, Chitrita
Radune, Diana
Kim, Maria
Sanka, Ravi
Brinkac, Lauren
Kariyawasam, Subhashinie
Shelton, Daniel
Fratamico, Pina M.
Kapur, Vivek
Feng, Peter C. H.
TI Whole genome sequencing of diverse Shiga toxin-producing and
non-producing Escherichia coli strains reveals a variety of virulence
and novel antibiotic resistance plasmids
SO PLASMID
LA English
DT Article
DE Genome sequencing; STEC; Plasmids; Antibiotic resistance; Virulence
genes
ID DNA-SEQUENCE; GENE; PREVALENCE; O157-H7; STEC
AB The genomes of a diverse set of Escherichia coli, including many Shiga toxin-producing strains of various serotypes were determined. A total of 39 plasmids were identified among these strains, and many carried virulence or putative virulence genes of Shiga toxin-producing E. coli strains, virulence genes for other pathogenic E. coli groups, and some had combinations of these genes. Among the novel plasmids identified were eight that carried resistance genes to aminoglycosides, carbapenems, penicillins, cephalosporins, chloramphenicol, dihydrofolate reductase inhibitors, sulfonamides, tetracyclines and resistance to heavy metals. Two of the plasmids carried six of these resistance genes and two novel IncHI2 plasmids were also identified. The results of this study showed that plasmids carrying diverse resistance and virulence genes of various pathogenic E. coli groups can be found in E. coli strains and serotypes regardless of the isolate's source and therefore, is consistent with the premise that these mobile elements carrying these traits may be broadly disseminated among E. coli. Published by Elsevier Inc.
C1 [Losada, Liliana; Radune, Diana; Kim, Maria; Sanka, Ravi; Brinkac, Lauren; Feng, Peter C. H.] J Craig Venter Inst, Rockville, MD USA.
[DebRoy, Chitrita; Kariyawasam, Subhashinie; Kapur, Vivek] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Shelton, Daniel] ARS, Environm Microbial & Food Safety Lab, USDA, Beltsville, MD USA.
[Fratamico, Pina M.] ARS, Eastern Reg Res Ctr, USDA, Wyndmoor, PA USA.
[Feng, Peter C. H.] US FDA, Div Microbiol, College Pk, MD USA.
RP Feng, PCH (reprint author), US FDA, HFS 711,5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM liliana@swhr.org; peter.feng@fda.hhs.gov
FU Department of Health and Human Services [HHSN272200900007C]; federal
funds from National Institute of Allergy and Infectious Diseases,
National Institutes of Health
FX This project has been funded in whole or in part with federal funds from
the National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Department of Health and Human Services under
contract number HHSN272200900007C. The authors also thank Mark Adams,
Derrick Fouts and William Nierman for their review of this manuscript.
NR 31
TC 2
Z9 2
U1 2
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0147-619X
EI 1095-9890
J9 PLASMID
JI Plasmid
PD JAN
PY 2016
VL 83
BP 8
EP 11
DI 10.1016/j.plasmid.2015.12.001
PG 4
WC Genetics & Heredity; Microbiology
SC Genetics & Heredity; Microbiology
GA DE8VG
UT WOS:000370914200002
PM 26746359
ER
PT J
AU Rutardottir, S
Karnaukhova, E
Nantasenamat, C
Songtawee, N
Prachayasittikul, V
Rajabi, M
Rosenlof, LW
Alayash, AI
Akerstrom, B
AF Rutardottir, Sigurbjorg
Karnaukhova, Elena
Nantasenamat, Chanin
Songtawee, Napat
Prachayasittikul, Virapong
Rajabi, Mohsen
Rosenlof, Lena Wester
Alayash, Abdu I.
Akerstrom, Bo
TI Structural and biochemical characterization of two heme binding sites on
alpha(1)-microglobulin using site directed mutagenesis and molecular
simulation
SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
LA English
DT Article
DE alpha(1)-Microglobulin; Heme; Site-directed mutagenesis; Molecular
simulation
ID LIPOCALIN PROTEIN FAMILY; ALPHA-TRYPSIN INHIBITOR; HEMOGLOBIN;
ALPHA-1-MICROGLOBULIN; RESIDUES; REDUCTION; COMPLEX; CELLS; LIVER; HC
AB Background: alpha(1)-Microglobulin (A1M) is a reductase and radical scavenger involved in physiological protection against oxidative damage. These functions were previously shown to be dependent upon cysteinyl-, C34, and lysyl side-chains, K(92, 118,130). A1M binds heme and the crystal structure suggests that C34 and H123 participate in a heme binding site. We have investigated the involvement of these five residues in the interactions with heme.
Methods: Four A1M-variants were expressed: with cysteine to serine substitution in position 34, lysine to threonine substitutions in positions (92, 118, 130), histidine to serine substitution in position 123 and a wt without mutations. Heme binding was investigated by tryptophan fluorescence quenching, UV-Vis spectrophotometry, circular dichroism, SPR, electrophoretic migration shift, gel filtration, catalase-like activity and molecular simulation.
Results: All A1M-variants bound to heme. Mutations in C34, H123 or K(92, 118, 130) resulted in significant absorbance changes, CD spectral changes, and catalase-like activity, suggesting involvement of these side groups in coordination of the heme-iron. Molecular simulation support a model with two heme-binding sites in A1M involving the mutated residues. Binding of the first heme induces allosteric stabilization of the structure predisposing for a better fit of the second heme.
Conclusions: The results suggest that one heme-binding site is located in the lipocalin pocket and a second binding site between loops 1 and 4. Reactions with the hemes involve the side-groups of C34, K(92, 118, 130) and H123.
General significance: The model provides a structural basis for the functional activities of A1M: heme binding activity of A1M. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Rutardottir, Sigurbjorg; Rosenlof, Lena Wester; Akerstrom, Bo] Lund Univ, Div Infect Med, Solvegatan 19, S-22184 Lund, Sweden.
[Karnaukhova, Elena; Rajabi, Mohsen; Alayash, Abdu I.] US FDA, Ctr Biol Evaluat & Res, Div Hematol Res & Review, Lab Biochem & Vasc Biol, Rockville, MD 20857 USA.
[Nantasenamat, Chanin; Songtawee, Napat] Mahidol Univ, Fac Med Technol, Ctr Data Min & Biomed Informat, Bangkok 10700, Thailand.
[Nantasenamat, Chanin; Prachayasittikul, Virapong] Mahidol Univ, Fac Med Technol, Dept Clin Microbiol & Appl Technol, Bangkok 10700, Thailand.
RP Akerstrom, B (reprint author), Lund Univ, Div Infect Med, Solvegatan 19, S-22184 Lund, Sweden.
EM sigurbjorg.rutardottir@med.lu.se
FU Swedish Medical Research Council (VR); Royal Physiographic Society in
Lund; Foundationsof Greta; Blood and Defense Network, Lund University;
Crafoord Foundation [20081029]; AIM Pharma AB; Research Career
Development Grant from Thailand Research Fund [RSA5780031]; National
Institutes of Health (NIH) [HL110900]; U.S. Food and Drug Administration
(MODSCI Grants); governmental ALF research grants; Foundations of Johan
Kock; Foundations of Alfred Osterlund
FX SR, LWR and BA are indebted to Maria E Johansson for invaluable
technical assistance. This work was supported by the Swedish Medical
Research Council (VR), governmental ALF research grants to Lund
University and Lund University Hospital, the Royal Physiographic Society
in Lund, the Foundations of Greta and Johan Kock, Alfred Osterlund, the
Blood and Defense Network, Lund University, the Crafoord Foundation
(20081029) and AIM Pharma AB. CN is supported by a Research Career
Development Grant (No. RSA5780031) from the Thailand Research Fund. MA
acknowledges the support from the National Institutes of Health (NIH)
under grants HL110900 and the U.S. Food and Drug Administration (MODSCI
Grants).
NR 43
TC 1
Z9 1
U1 3
U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-9639
EI 0006-3002
J9 BBA-PROTEINS PROTEOM
JI BBA-Proteins Proteomics
PD JAN
PY 2016
VL 1864
IS 1
BP 29
EP 41
DI 10.1016/j.bbapap.2015.10.002
PG 13
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA DE2NP
UT WOS:000370464300004
PM 26497278
ER
PT J
AU Zhao, S
Tyson, GH
Chen, Y
Li, C
Mukherjee, S
Young, S
Lam, C
Folster, JP
Whichard, JM
McDermott, PF
AF Zhao, S.
Tyson, G. H.
Chen, Y.
Li, C.
Mukherjee, S.
Young, S.
Lam, C.
Folster, J. P.
Whichard, J. M.
McDermott, P. F.
TI Whole-Genome Sequencing Analysis Accurately Predicts Antimicrobial
Resistance Phenotypes in Campylobacter spp.
SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY
LA English
DT Article
ID MACROLIDE RESISTANCE; ESCHERICHIA-COLI; BETA-LACTAMASE; AGAR DILUTION;
TETRACYCLINE RESISTANCE; ANTIBIOTIC-RESISTANCE; BROTH MICRODILUTION;
NUCLEOTIDE-SEQUENCE; C-JEJUNI; GENES
AB The objectives of this study were to identify antimicrobial resistance genotypes for Campylobacter and to evaluate the correlation between resistance phenotypes and genotypes using in vitro antimicrobial susceptibility testing and whole-genome sequencing (WGS). A total of 114 Campylobacter species isolates (82 C. coli and 32 C. jejuni) obtained from 2000 to 2013 from humans, retail meats, and cecal samples from food production animals in the United States as part of the National Antimicrobial Resistance Monitoring System were selected for study. Resistance phenotypes were determined using broth microdilution of nine antimicrobials. Genomic DNA was sequenced using the Illumina MiSeq platform, and resistance genotypes were identified using assembled WGS sequences through blastx analysis. Eighteen resistance genes, including tet(O), bla(OXA-61), catA, lnu(C), aph(2 '')-Ib, aph(2 '')-Ic, aph(2')-If, aph(2 '')-Ig, aph(2 '')-Ih, aac(6')-Ie-aph(2 '')-Ia, aac(6')-Ie-aph(2 '')-If, aac(6')-Im, aadE, sat4, ant(6'), aad9, aph(3')-Ic, and aph(3')-IIIa, and mutations in two housekeeping genes (gyrA and 23S rRNA) were identified. There was a high degree of correlation between phenotypic resistance to a given drug and the presence of one or more corresponding resistance genes. Phenotypic and genotypic correlation was 100% for tetracycline, ciprofloxacin/nalidixic acid, and erythromycin, and correlations ranged from 95.4% to 98.7% for gentamicin, azithromycin, clindamycin, and telithromycin. All isolates were susceptible to florfenicol, and no genes associated with florfenicol resistance were detected. There was a strong correlation (99.2%) between resistance genotypes and phenotypes, suggesting that WGS is a reliable indicator of resistance to the nine antimicrobial agents assayed in this study. WGS has the potential to be a powerful tool for antimicrobial resistance surveillance programs.
C1 [Zhao, S.; Tyson, G. H.; Chen, Y.; Li, C.; Mukherjee, S.; Young, S.; Lam, C.; McDermott, P. F.] US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD USA.
[Folster, J. P.; Whichard, J. M.] Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Atlanta, GA USA.
RP Zhao, S (reprint author), US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD USA.
EM shaohua.zhao@fda.hhs.gov
FU U.S. Food and Drug Administration
FX This work was supported by the U.S. Food and Drug Administration with
internal funds as part of routine work.
NR 37
TC 9
Z9 10
U1 4
U2 15
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0099-2240
EI 1098-5336
J9 APPL ENVIRON MICROB
JI Appl. Environ. Microbiol.
PD JAN
PY 2016
VL 82
IS 2
BP 459
EP 466
DI 10.1128/AEM.02873-15
PG 8
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA DC7BL
UT WOS:000369373200005
PM 26519386
ER
PT J
AU Deuel, JW
Schaer, CA
Boretti, FS
Opitz, L
Garcia-Rubio, I
Baek, JH
Spahn, DR
Buehler, PW
Schaer, DJ
AF Deuel, J. W.
Schaer, C. A.
Boretti, F. S.
Opitz, L.
Garcia-Rubio, I.
Baek, J. H.
Spahn, D. R.
Buehler, P. W.
Schaer, D. J.
TI Hemoglobinuria-related acute kidney injury is driven by intrarenal
oxidative reactions triggering a heme toxicity response
SO CELL DEATH & DISEASE
LA English
DT Article
ID UNFOLDED PROTEIN RESPONSE; SICKLE-CELL-DISEASE; RED-BLOOD-CELL;
GUINEA-PIGS; ER STRESS; HAPTOGLOBIN; DAMAGE; HEMOLYSIS; DEATH;
PATHOPHYSIOLOGY
AB Intravascular hemolysis can result in hemoglobinuria with acute kidney injury. In this study we systematically explored two in vivo animal models and a related cell culture system to identify hemoglobinuria-triggered damage pathways. In models of stored blood transfusion and hemoglobin (Hb) exposure in guinea pigs and beagle dogs we found that hemoglobinuria led to intrarenal conversion of ferrous Hb(Fe2+) to ferric Hb(Fe3+), accumulation of free heme and Hb-cross-linking products, enhanced 4-hydroxynonenal reactivity in renal tissue, and acute tubule injury. These changes were associated in guinea pigs with activation of a renal cortex gene expression signature indicative of oxidative stress and activation of the unfolded protein response (UPR). Tubule cells of hemolytic animals demonstrated enhanced protein expression of heme oxygenase and heat shock protein and enhanced expression of acute kidney injury-related neutrophil gelatinase-associated lipocalin. These adverse changes were completely prevented by haptoglobin treatment. The in vivo findings were extrapolated to a MS-based proteome analysis of SILAC-labeled renal epithelial cells that were exposed to free heme within a concentration range estimate of renal tubule heme exposure. These experiments confirmed that free heme is a likely trigger of tubule barrier deregulation and oxidative cell damage and reinforced the hypothesis that uncontrolled free heme could trigger the UPR as an important pathway of renal injury during hemoglobinuria.
C1 [Deuel, J. W.; Schaer, C. A.; Schaer, D. J.] Univ Zurich, Div Internal Med, Zurich, Switzerland.
[Schaer, C. A.; Spahn, D. R.] Univ Zurich, Inst Anesthesiol, Zurich, Switzerland.
[Boretti, F. S.] Univ Zurich, Clin Small Anim Internal Med, Zurich, Switzerland.
[Opitz, L.] Univ Zurich, Swiss Fed Inst Technol Zurich, Funct Genom Ctr Zurich, Zurich, Switzerland.
[Garcia-Rubio, I.] ETH, Phys Chem Lab, CH-8092 Zurich, Switzerland.
[Garcia-Rubio, I.] Ctr Univ Def, Carretera Huesca, Zaragoza, Spain.
[Baek, J. H.; Buehler, P. W.] US FDA, Lab Biochem & Vasc Biol, CBER, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
[Schaer, D. J.] Univ Zurich, Inst Evolutionary Med, Zurich, Switzerland.
RP Buehler, PW (reprint author), US FDA, Lab Biochem & Vasc Biol, CBER, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.; Schaer, DJ (reprint author), Univ Zurich Hosp, Div Internal Med, CH-8091 Zurich, Switzerland.
EM paul.buehler@fda.hhs.gov; dominik.schaer@usz.ch
OI Deuel, Jeremy/0000-0002-5409-7712
FU Swiss National Science Foundation [31003A/138500]; University of Zurich
Research Priority Program 'Integrative Human Physiology'; Swiss Federal
Commission for Technology and Innovation; Ministry of Health
(Gesundheitsdirektion) of the Canton of Zurich, for Highly Specialized
Medicine
FX This work was supported by the Swiss National Science Foundation
(31003A/138500 to DJS), the University of Zurich Research Priority
Program 'Integrative Human Physiology', the Swiss Federal Commission for
Technology and Innovation, and the Ministry of Health
(Gesundheitsdirektion) of the Canton of Zurich, for Highly Specialized
Medicine (Patient Blood Management to DRS).
NR 43
TC 4
Z9 4
U1 4
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD JAN
PY 2016
VL 7
AR e2064
DI 10.1038/cddis.2015.392
PG 12
WC Cell Biology
SC Cell Biology
GA DC4HG
UT WOS:000369181000024
PM 26794659
ER
PT J
AU Popp, NA
Yu, DK
Green, B
Chew, EY
Ning, BT
Chan, CC
Tuo, JS
AF Popp, Nicholas A.
Yu, Dianke
Green, Bridgett
Chew, Emily Y.
Ning, Baitang
Chan, Chi-Chao
Tuo, Jingsheng
TI Functional single nucleotide polymorphism in IL-17A 3 untranslated
region is targeted by miR-4480 in vitro and may be associated with
age-related macular degeneration
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Article
DE microRNA; age-related macular degeneration; inflammation; IL-17A; SNPs;
epigenetics; genetics
ID EYE DISEASE; GENETIC ASSOCIATION; NLRP3 INFLAMMASOME; RISK-FACTORS;
CELLS; MICRORNAS; AUTOIMMUNITY; INDUCTION; REPLICATE; UVEITIS
AB Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in the elderly. Genetic factors contributing to AMD include single nucleotide polymorphisms (SNPs) in immune-related genes including CFH, C2, CFI, C9, and C3, thus implicating these pathways in AMD pathogenesis. MicroRNAs (miRNAs) are powerful regulators of gene expression and execute this function by binding to the 3 untranslated region (3UTR) of target mRNAs, leading to mRNA degradation. In this study, we searched for the possible association of SNPs in the 3UTR region of IL-17A, a gene implicated in AMD pathogenesis without any previous SNP association with AMD. Using two independent sample cohorts of Caucasian subjects, six SNPs in the IL-17A 3-UTR were selected for genotyping based on bioinformatic predictions of the SNP effect on microRNA binding. The SNP rs7747909 was found to be associated with AMD (P<0.05) in the NEI cohort, using a dominant model logistic regression. Luciferase reporter gene assays and RNA electrophoretic mobility shift assays were performed using ARPE-19 cells to confirm the preferential binding of microRNAs to the major allele of the SNP. Our findings support the hypothesis that microRNA-mediated gene dysregulation may play a role in the pathogenesis of AMD. Environ. Mol. Mutagen. 57:58-64, 2016. (c) 2015 Wiley Periodicals, Inc.
C1 [Popp, Nicholas A.; Chan, Chi-Chao; Tuo, Jingsheng] NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Yu, Dianke; Green, Bridgett; Ning, Baitang] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
RP Tuo, JS (reprint author), NEI, Immunopathol Sect, Immunol Lab, 10 Ctr Dr,Bldg 10,Room 10N103, Bethesda, MD 20892 USA.
EM jingsheng.tuo@nih.gov
FU NEI Intramural Research Program
FX Grant sponsor: NEI Intramural Research Program.
NR 38
TC 0
Z9 0
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
EI 1098-2280
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD JAN
PY 2016
VL 57
IS 1
BP 58
EP 64
DI 10.1002/em.21982
PG 7
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA DB7MT
UT WOS:000368700300007
PM 26765636
ER
PT J
AU Revollo, J
Petibone, DM
McKinzie, P
Knox, B
Morris, SM
Ning, BT
Dobrovolsky, VN
AF Revollo, Javier
Petibone, Dayton M.
McKinzie, Page
Knox, Bridgett
Morris, Suzanne M.
Ning, Baitang
Dobrovolsky, Vasily N.
TI Whole genome and normalized mRNA sequencing reveal genetic status of
TK6, WTK1, and NH32 human B-lymphoblastoid cell lines
SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
LA English
DT Article
DE Next generation sequencing (NGS); p53; FTH1; TPMT*3A; NQO1*2; Human
B-lymphoblastoid cells
ID THIOPURINE S-METHYLTRANSFERASE; IN-VITRO MICRONUCLEUS; THYMIDINE KINASE
LOCUS; NAD(P)H-QUINONE OXIDOREDUCTASE-1; MUTAGENIC RESPONSES; MUTATION
ASSAY; IRON OVERLOAD; P53 STATUS; X-RAYS; HETEROZYGOSITY
AB Closely related TK6, WTK1, and NH32 human B-lymphoblastoid cell lines differ in their p53 functional status. These lines are used frequently in genotoxicity studies and in studies aimed at understanding the role of p53 in DNA repair. Despite their routine use, little is known about the genetic status of these cells. To provide insight into their genetic composition, we sequenced and analyzed the entire genome of TK6 cells, as well as the normalized transcriptomes of TK6, WTK1, and NH32 cells. Whole genome sequencing (WGS) identified 21,561 genes and 5.17 x 10(6) small variants. Within the small variants, 50.54% were naturally occurring single nucleotide polymorphisms (SNPs) and 49.46% were mutations. The mutations were comprised of 92.97% single base-pair substitutions and 7.03% insertions or deletions (indels). The number of predicted genes, SNPs, and small mutations are similar to frequencies observed in the human population in general. Normalized mRNA-seq analysis identified the expression of transcripts bearing SNPs or mutations for TK6, WTK1, and NH32 as 2.88%, 2.04%, and 1.71%, respectively, and several of the variant transcripts identified appear to have important implications in genetic toxicology. These include a single base deletion mutation in the ferritin heavy chain gene (FTH1) resulting in a frame shift and protein truncation in TK6 that impairs iron metabolism. SNPs in the thiopurine S-methyltransferase (TPMT) gene (TPMT*3A SNP), and in the xenobiotic metabolizing enzyme, NADPH quinine oxidoreductase 1 (NQO1) gene (NQO1*2 SNP), are both associated with decreased enzyme activity. The clinically relevant TPMT*3A and NQO1*2 SNPs can make these cell lines useful in pharmacogenetic studies aimed at improving or tailoring drug treatment regimens that minimize toxicity and enhance efficacy. Published by Elsevier B.V.
C1 [Revollo, Javier; Petibone, Dayton M.; McKinzie, Page; Morris, Suzanne M.; Dobrovolsky, Vasily N.] US FDA, Div Genet & Mol Toxicol, NCTR, Jefferson, AR 72079 USA.
[Knox, Bridgett; Ning, Baitang] US FDA, Div Syst Biol, NCTR, Jefferson, AR 72079 USA.
RP Petibone, DM (reprint author), 3900 NCTR Rd,HFT 120, Jefferson, AR 72079 USA.
EM Dayton.petibone@fda.hhs.gov
FU FDA
FX All research costs were paid for by internal FDA funds.
NR 51
TC 1
Z9 1
U1 80
U2 84
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1383-5718
EI 1879-3592
J9 MUTAT RES-GEN TOX EN
JI Mutat. Res. Genet. Toxicol. Environ. Mutagen.
PD JAN 1
PY 2016
VL 795
BP 60
EP 69
DI 10.1016/j.mrgentox.2015.11.006
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA DC8FA
UT WOS:000369454100007
PM 26774668
ER
PT J
AU Dobrovolsky, VN
Pacheco-Martinez, MM
McDaniel, LP
Pearce, MG
Ding, W
AF Dobrovolsky, Vasily N.
Monserrat Pacheco-Martinez, M.
Patrice McDaniel, L.
Pearce, Mason G.
Ding, Wei
TI In vivo genotoxicity assessment of acrylamide and glycidyl methacrylate
SO FOOD AND CHEMICAL TOXICOLOGY
LA English
DT Article
DE Red blood cells; Reticulocytes; Flow cytometry; Micronucleus test; The
Pig-a assay; The Comet assay
ID CHEMICAL-STRUCTURE; MUTAGENICITY; GLYCIDAMIDE; CARCINOGENICITY;
SALMONELLA; MICE; EPOXIDES; CELLS; ASSAY; RATS
AB Acrylamide (ACR) and glycidyl methacrylate (GMA) are structurally related compounds used for making polymers with various properties. Both chemicals can be present in food either as a byproduct of processing or a constituent of packaging. We performed a comprehensive evaluation of ACR and GMA genotoxicity in Fisher 344 rats using repeated gavage administrations. Clastogenicity was measured by scoring micronucleated (MN) erythrocytes from peripheral blood, DNA damage in liver, bone marrow and kidneys was measured using the Comet assay, and gene mutation was measured using the red blood cell (RBC) and reticulocyte Pig-a assay. A limited histopathology evaluation was performed in order to determine levels of cytotoxicity. Doses of up to 20 mg/kg/day of ACR and up to 250 mg/kg/day of GMA were used. ACR treatment resulted in DNA damage in the liver, but not in the bone marrow. While ACR was not a clastogen, it was a weak (equivocal) mutagen in the cells of bone marrow. GMA caused DNA damage in the cells of bone marrow, liver and kidney, and induced MN reticulocytes and Pig-a mutant RBCs in a dose-dependent manner. Collectively, our data suggest that both compounds are in vivo genotoxins, but the genotoxicity of ACR is tissue specific. Published by Elsevier Ltd.
C1 [Dobrovolsky, Vasily N.; Patrice McDaniel, L.; Pearce, Mason G.; Ding, Wei] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA.
[Monserrat Pacheco-Martinez, M.] Univ Autonoma Metropolitana Iztapalapa, Dept Ciencias Salud, Mexico City 09340, DF, Mexico.
RP Dobrovolsky, VN (reprint author), 3900 NCTR Rd,HFT-120, Jefferson, AR 72079 USA.
EM vasily.dobrovolsky@fda.hhs.gov
FU Consejo Nacional de Ciencia y Tecnologia (CONACyT; Mexico); Oak Ridge
Institute for Science and Education
FX The authors would like to thank Dr. Robert H. Heflich for valuable
comments on the experimental design, data analysis and interpretation.
M.M. Pacheco-Martinez's participation was partially supported by Consejo
Nacional de Ciencia y Tecnologia (CONACyT; Mexico) and by the Oak Ridge
Institute for Science and Education through an interagency agreement
between the U.S. Department of Energy and the U.S. FDA.
NR 19
TC 6
Z9 6
U1 6
U2 20
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-6915
EI 1873-6351
J9 FOOD CHEM TOXICOL
JI Food Chem. Toxicol.
PD JAN
PY 2016
VL 87
BP 120
EP 127
DI 10.1016/j.fct.2015.12.006
PG 8
WC Food Science & Technology; Toxicology
SC Food Science & Technology; Toxicology
GA DC1HA
UT WOS:000368966200013
PM 26686995
ER
PT J
AU Tesfamariam, B
AF Tesfamariam, Belay
TI Involvement of platelets in tumor cell metastasis
SO PHARMACOLOGY & THERAPEUTICS
LA English
DT Review
DE Platelet-tumor loop; Epithelial-mesenchymal-like transition; Metastasis;
Immune evasion; Angiogenesis; Microparticles
ID ENDOTHELIAL GROWTH-FACTOR; BREAST-CANCER; IN-VIVO; LUNG METASTASIS;
HEPATOCELLULAR-CARCINOMA; HEMATOGENOUS-METASTASIS; IMPROVES SURVIVAL;
ALPHA-GRANULES; P-SELECTIN; INHIBITION
AB Extensive experimental evidence indicates that platelets contribute to tumor cell proliferation and metastasis through direct interactions and secreted bioactive proteins. Activated platelets release secretory factors that promote growth factors, chemokines, proangiogenic regulatory proteins, proteolytic enzymes and microparticles within the microenvironment to promote tumor cell growth and invasion. Furthermore, the formation of platelet-tumor cell heteroaggregates by integrin alpha(IIb)beta(3) (glycoprotein IIb/IIIa) bridging plays an important role in tumor survival by forming a physical shield around tumor cells, and thereby protecting circulating tumor cells from immune-mediated lysis by natural killer (NK) cells. Tumor cells directly activate platelets by enhancing expression of surface integrins, selectins and secretion of granules, which amplify platelet aggregation. In addition to the physical coating of tumor cells, platelets release transforming growth factor-beta 1 (TGF-beta 1) that induces phenotypic changes of epithelial to mesenchymal-like transition of tumor cells, thereby facilitating their extravasation and dissemination to distant sites during metastasis. Thus, there is a complex interplay between platelet induced tumor growth and tumor cell-induced platelet activation, with the involvement of multiple components within the tumor microenvironment that enhance metastasis. This review describes the intimate reciprocal cross-talk between platelets and tumor cells, and the various signaling pathways involved in tumor amplification, which may be potential therapeutic targets to disrupt the platelet-tumor loop to reduce metastatic processes. Published by Elsevier Inc.
C1 [Tesfamariam, Belay] US FDA, Div Cardiovasc & Renal Prod, CDER, 10903 New Hampshire Ave,Bldg 22,Rm 4176,, Silver Spring, MD 20993 USA.
RP Tesfamariam, B (reprint author), US FDA, Div Cardiovasc & Renal Prod, CDER, 10903 New Hampshire Ave,Bldg 22,Rm 4176,, Silver Spring, MD 20993 USA.
EM belay.tesfamariam@fda.hhs.gov
NR 66
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Z9 8
U1 8
U2 19
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0163-7258
J9 PHARMACOL THERAPEUT
JI Pharmacol. Ther.
PD JAN
PY 2016
VL 157
BP 112
EP 119
DI 10.1016/j.pharmthera.2015.11.005
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DC1DN
UT WOS:000368957100008
PM 26615781
ER
PT J
AU Mewton, N
Strauss, DG
Rizzi, P
Verrier, RL
Liu, CY
Tereshchenko, LG
Nearing, B
Volpe, GJ
Marchlinski, FE
Moxley, J
Killian, T
Wu, KC
Spooner, P
Lima, JAC
AF Mewton, Nathan
Strauss, David G.
Rizzi, Patricia
Verrier, Richard L.
Liu, Chia Ying
Tereshchenko, Larisa G.
Nearing, Bruce
Volpe, Gustavo J.
Marchlinski, Francis E.
Moxley, John
Killian, Tony
Wu, Katherine C.
Spooner, Peter
Lima, Joao A. C.
TI Screening for Cardiac Magnetic Resonance Scar Features by 12-Lead ECG,
in Patients with Preserved Ejection Fraction
SO ANNALS OF NONINVASIVE ELECTROCARDIOLOGY
LA English
DT Article
DE magnetic resonance imaging; death; sudden; screening; myocardial scar;
T-wave alternans
ID T-WAVE ALTERNANS; INFARCT TISSUE HETEROGENEITY; RISK STRATIFICATION;
HYPERTROPHIC CARDIOMYOPATHY; VENTRICULAR-TACHYCARDIA; ISCHEMIC
CARDIOMYOPATHY; DILATED CARDIOMYOPATHY; MYOCARDIAL SCAR; DEATH;
MORTALITY
AB BackgroundIncreased QRS score and wide spatial QRS-T angle are independent predictors of cardiovascular mortality in the general population. Our main objective was to assess whether a QRS score 5 and/or QRS-T angle 105 degrees enable screening of patients for myocardial scar features.
MethodsSeventy-seven patients of age 70 years with QRS score 5 and/or spatial QRS-T angle 105 degrees as well as left ventricular ejection fraction (LVEF) >35% were enrolled in the study. All participants underwent complete clinical examination, signal-averaged ECG (SAECG), 30-minute ambulatory ECG recording for T-wave alternans (TWA), and late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Relationship between QRS score, QRS-T angle with scar presence and pattern, as well as gray zone, core, and total scar size by LGE-CMR were assessed.
ResultsMyocardial scar was present in 41 (53%) patients, of whom 19 (46%) exhibited a typical ischemic pattern. QRS score but not QRS-T angle was related to total scar size and gray zone size (R-2 = 0.12, P = 0.002; R-2 = 0.17; P 0.0001, respectively). Patients with QRS scores 6 had significantly greater myocardial scar and gray zone size, increased QRS duration and QRS-T angle, a higher prevalence of late potentials (LPs) presence, increased LV end-diastolic volume and decreased LVEF. There was a significant independent and positive association between TWA value and total scar (P = 0.001) and gray zone size (P = 0.01).
ConclusionPatients with preserved LVEF and myocardial scar by CMR also have electrocardiographic features that could be involved in ventricular arrhythmogenesis.
C1 [Mewton, Nathan; Rizzi, Patricia; Liu, Chia Ying; Tereshchenko, Larisa G.; Volpe, Gustavo J.; Moxley, John; Wu, Katherine C.; Spooner, Peter; Lima, Joao A. C.] Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA.
[Mewton, Nathan] Hosp Civils Lyon, Ctr Invest Clin, Hop Cardiovasc Louis Pradel, Bron, France.
[Strauss, David G.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Verrier, Richard L.; Nearing, Bruce] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Marchlinski, Francis E.; Killian, Tony] Hosp Univ Penn, Dept Med, Div Cardiol, Philadelphia, PA 19104 USA.
RP Lima, JAC (reprint author), Johns Hopkins Univ Hosp, Div Cardiol, 600 N Wolfe St,Blalock 524, Baltimore, MD 21287 USA.
EM jlima@jhmi.edu
OI Tereshchenko, Larisa/0000-0002-6976-1313
FU NIH Cardiac Translational Research Implementation Program (CTRIP) [P20];
French Federation of Cardiology; Leducq Foundation Alliance against
Sudden Cardiac Death Network Award
FX NIH Cardiac Translational Research Implementation Program (CTRIP) P20 to
Johns Hopkins Hospital, Joao Lima, M.D., Principal Investigator. Nathan
Mewton was supported by a Postdoctoral Research Grant from the French
Federation of Cardiology and also received support from the Leducq
Foundation Alliance against Sudden Cardiac Death Network Award to Johns
Hopkins University.
NR 34
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1082-720X
EI 1542-474X
J9 ANN NONINVAS ELECTRO
JI Ann. Noninvasive Electrocardiol.
PD JAN
PY 2016
VL 21
IS 1
BP 49
EP 59
DI 10.1111/anec.12264
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DB9IN
UT WOS:000368829700006
PM 26806840
ER
PT J
AU Wang, Y
Salazar, JK
AF Wang, Yun
Salazar, Joelle K.
TI Culture-Independent Rapid Detection Methods for Bacterial Pathogens and
Toxins in Food Matrices
SO COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY
LA English
DT Review
DE biosensors; detection; foodborne bacterial pathogens; food matrices;
food safety
ID ESCHERICHIA-COLI O157-H7; SURFACE-PLASMON RESONANCE;
POLYMERASE-CHAIN-REACTION; REAL-TIME PCR; MEDIATED ISOTHERMAL
AMPLIFICATION; STAPHYLOCOCCAL-ENTEROTOXIN-B; SEQUENCE-BASED
AMPLIFICATION; LABEL-FREE DETECTION; IN-GROUND BEEF; ELECTROCHEMICAL
IMPEDANCE IMMUNOSENSOR
AB Rapid detection of bacterial pathogens and toxins in foods is necessary to provide real-time results to mitigate foodborne illness outbreaks. Cultural enrichment methods, although the most widely used, are time-consuming and therefore inadequate for rapid pathogen detection from food samples. The development of novel "rapid" detection methods has decreased detection time dramatically. This review presents an overview of detection methods for various foodborne pathogens, including Listeria monocytogenes, Salmonella enterica, and shiga toxin-producing Escherichia coli, and bacterial toxins in food matrices, with emphasis on those methods which do not require cultural enrichment. Discussed methods include nucleic acid-, immunological-, and biosensor-based techniques. A summary of each type of detection method is given, including referenced methods from the literature. Since these discussed methods do not require cultural enrichment, there is a higher probability of interference from the food matrices. Therefore, the review also discusses the potential interference of food components on detection methods and addresses preprocessing strategies to overcome matrix associated inhibition and to concentrate low quantities of pathogens and toxins in food. Development of rapid and sensitive detection technologies advances and ensures public health safety and security.
C1 [Wang, Yun; Salazar, Joelle K.] US FDA, Div Food Proc Sci & Technol, Bedford Pk, IL 60501 USA.
RP Wang, Y (reprint author), US FDA, Div Food Proc Sci & Technol, Bedford Pk, IL 60501 USA.
EM Yun.Wang2@fda.hhs.gov
RI Wang, Yun/G-8899-2016
FU Oak Ridge Institute for Science and Education Research Participation
Program
FX The authors gratefully thank Mary Lou Tortorello for helpful discussions
while preparing the manuscript. YW and JKS were supported by the Oak
Ridge Institute for Science and Education Research Participation Program
to the U.S. Food and Drug Administration. The sponsors had no role in
the study design, data collection, and analysis, decision to publish, or
preparation of the manuscript.
NR 211
TC 6
Z9 6
U1 26
U2 69
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1541-4337
J9 COMPR REV FOOD SCI F
JI Compr. Rev. Food. Sci. Food Saf.
PD JAN
PY 2016
VL 15
IS 1
BP 183
EP 205
DI 10.1111/1541-4337.12175
PG 23
WC Food Science & Technology
SC Food Science & Technology
GA DB2QQ
UT WOS:000368354500010
ER
PT J
AU Xu, JL
Audet, C
DiLiberti, CE
Hauck, WW
Montague, TH
Parr, AF
Potvin, D
Schuirmann, DJ
AF Xu, Jialin
Audet, Charles
DiLiberti, Charles E.
Hauck, Walter W.
Montague, Timothy H.
Parr, Alan F.
Potvin, Diane
Schuirmann, Donald J.
TI Optimal adaptive sequential designs for crossover bioequivalence studies
SO PHARMACEUTICAL STATISTICS
LA English
DT Article
DE sequential design; sample size re-estimation; adaptive design;
bioequivalence
ID TRIALS; TESTS
AB In prior works, this group demonstrated the feasibility of valid adaptive sequential designs for crossover bioequivalence studies. In this paper, we extend the prior work to optimize adaptive sequential designs over a range of geometric mean test/reference ratios (GMRs) of 70-143% within each of two ranges of intra-subject coefficient of variation (10-30% and 30-55%). These designs also introduce a futility decision for stopping the study after the first stage if there is sufficiently low likelihood of meeting bioequivalence criteria if the second stage were completed, as well as an upper limit on total study size. The optimized designs exhibited substantially improved performance characteristics over our previous adaptive sequential designs. Even though the optimized designs avoided undue inflation of type I error and maintained power at 80%, their average sample sizes were similar to or less than those of conventional single stage designs. Copyright (c) 2015 John Wiley & Sons, Ltd.
C1 [Xu, Jialin] Merck & Co Inc, Upper Gwynedd, PA USA.
[Audet, Charles] Gerad, Montreal, PQ H3C 3A7, Canada.
[Audet, Charles] Ecole Polytech, Montreal, PQ H3C 3A7, Canada.
[DiLiberti, Charles E.; Hauck, Walter W.] Montclair Bioequivalence Serv LLC, Montclair, NJ USA.
[Montague, Timothy H.] GlaxoSmithKline Inc, King Of Prussia, PA USA.
[Parr, Alan F.] GlaxoSmithKline Inc, Durham, NC USA.
[Potvin, Diane] Excelsus Stat Inc, Montreal, PQ, Canada.
[Schuirmann, Donald J.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Hauck, WW (reprint author), Sycamore Consulting LLC, POB 604, New Hope, PA 18938 USA.
EM Walter.Hauck@comcast.net
RI Audet, Charles/A-7278-2010
OI Audet, Charles/0000-0002-3043-5393
FU Product Quality Research Institute (PQRI)
FX The authors would like to thank the Product Quality Research Institute
(PQRI) for its financial support and encouragement in this work.
NR 16
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U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1539-1604
EI 1539-1612
J9 PHARM STAT
JI Pharm. Stat.
PD JAN-FEB
PY 2016
VL 15
IS 1
BP 15
EP 27
DI 10.1002/pst.1721
PG 13
WC Pharmacology & Pharmacy; Statistics & Probability
SC Pharmacology & Pharmacy; Mathematics
GA DB5TZ
UT WOS:000368577800002
PM 26538182
ER
PT J
AU Lin, JJ
Gamalo-Siebers, M
Tiwari, R
AF Lin, Junjing
Gamalo-Siebers, Margaret
Tiwari, Ram
TI Non-inferiority and networks: inferring efficacy from a web of data
SO PHARMACEUTICAL STATISTICS
LA English
DT Article
DE meta-analysis; power prior; Dirichlet process prior; comparative
effectiveness; model selection
ID RANDOMIZED CONTROLLED-TRIALS; MIXED TREATMENT COMPARISONS; POWER PRIOR
DISTRIBUTIONS; ACTIVE-CONTROL TRIALS; CARE DECISION-MAKING; ISPOR
TASK-FORCE; MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; ANTITHROMBOTIC
THERAPY; NONPARAMETRIC PROBLEMS
AB In the absence of placebo-controlled trials, the efficacy of a test treatment can be alternatively examined by showing its non-inferiority to an active control; that is, the test treatment is not worse than the active control by a pre-specified margin. The margin is based on the effect of the active control over placebo in historical studies. In other words, the non-inferiority setup involves a network of direct and indirect comparisons between test treatment, active controls, and placebo. Given this framework, we consider a Bayesian network meta-analysis that models the uncertainty and heterogeneity of the historical trials into the non-inferiority trial in a data-driven manner through the use of the Dirichlet process and power priors. Depending on whether placebo was present in the historical trials, two cases of non-inferiority testing are discussed that are analogs of the synthesis and fixed-margin approach. In each of these cases, the model provides a more reliable estimate of the control given its effect in other trials in the network, and, in the case where placebo was only present in the historical trials, the model can predict the effect of the test treatment over placebo as if placebo had been present in the non-inferiority trial. It can further answer other questions of interest, such as comparative effectiveness of the test treatment among its comparators. More importantly, the model provides an opportunity for disproportionate randomization or the use of small sample sizes by allowing borrowing of information from a network of trials to draw explicit conclusions on non-inferiority. Copyright (c) 2015 John Wiley & Sons, Ltd.
C1 [Gamalo-Siebers, Margaret] Food & Drug Adm, Ctr Food Safety & Appl Nutr, Off Analyt & Outreach, College Pk, MD 20740 USA.
[Lin, Junjing] Univ Calif Santa Barbara, Dept Stat & Appl Probabil, Santa Barbara, CA 93106 USA.
[Tiwari, Ram] Food & Drug Adm, Office Biostat, Silver Spring, MD USA.
RP Gamalo-Siebers, M (reprint author), Food & Drug Adm, Ctr Food Safety & Appl Nutr, Off Analyt & Outreach, College Pk, MD 20740 USA.
EM margaret.gamalo@fda.hhs.gov
NR 59
TC 0
Z9 0
U1 3
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1539-1604
EI 1539-1612
J9 PHARM STAT
JI Pharm. Stat.
PD JAN-FEB
PY 2016
VL 15
IS 1
BP 54
EP 67
DI 10.1002/pst.1729
PG 14
WC Pharmacology & Pharmacy; Statistics & Probability
SC Pharmacology & Pharmacy; Mathematics
GA DB5TZ
UT WOS:000368577800006
PM 26639225
ER
PT J
AU Zhang, YT
Kantor, MA
Juan, WY
AF Zhang, Yuanting
Kantor, Mark A.
Juan, WenYen
TI Usage and Understanding of Serving Size Information on Food Labels in
the United States
SO AMERICAN JOURNAL OF HEALTH PROMOTION
LA English
DT Article
DE Nutrition Label; Serving Size; Survey Research; Nutrition Education;
Prevention Research
ID PORTION SIZES; US ADULTS; CONSUMERS; LITERACY; GUIDANCE
AB Purpose. To investigate consumer understanding and usage of serving size (SS) information on Nutrition Facts (NF) labels.
Design. We analyzed three data sources: (1) US. Food and Drug Administration (FDA) Health and Diet Survey (HDS) 1994 (n = 1945), 1995 (n = 1001), and 2008 (n = 2584); (2) National Health and Nutrition Examination Survey (NHANES) 2005-2006 and 2007 2008 (n = 10,750); and (3) 2011 FDA Nutrition Facts Label Experimental Study (NFLES) (n = 9493). Data from FDA are cross-sectional and we focused on usage and meaning of SS.
Setting. United States.
Subjects. Adults (18+ years).
Measures. Both HDS and NHANES addressed how often participants used SS information and HDS also asked how SS is determined. Both NHANES and NFLES contained similar questions on the meaning of SS but NFLES also included an open-ended response option.
Analysis. We included both quantitative and qualitative measures. Questions were analyzed by demographic variables and body mass index with frequencies, cross-tabulations, and chi(2) statistics reported.
Results. HDS showed that the percentage of consumers who used SS information often or sometimes increased from 54% in 1994 to 64% in 2008. NHANES and NFLES data indicated that a majority of respondents had misinterpreted the meaning of SS. Women and obese individuals were more likely to use SS often or sometimes, but were also more likely to misinterpret the meaning of SS. A small subsample of NFLES participants expressed a distrust of the SS information.
Conclusion. There is a widespread misunderstanding about SS, suggesting the need for clearer NF labels or enhanced education efforts.
C1 [Zhang, Yuanting] US FDA, Off Analyt & Outreach, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Kantor, Mark A.; Juan, WenYen] US FDA, Off Nutr Labeling & Dietary Supplements, College Pk, MD 20740 USA.
RP Zhang, YT (reprint author), US FDA, Off Analyt & Outreach, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 013, College Pk, MD 20740 USA.
EM Yuanting.Zhang@fda.hhs.gov
NR 27
TC 1
Z9 1
U1 5
U2 11
PU AMER JOURNAL HEALTH PROMOTION INC
PI TROY
PA PO BOX 1254, TROY, MI 48099-1254 USA
SN 0890-1171
EI 2168-6602
J9 AM J HEALTH PROMOT
JI Am. J. Health Promot.
PD JAN-FEB
PY 2016
VL 30
IS 3
BP 181
EP 187
DI 10.4278/ajhp.130117-QUAN-30
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DA8JC
UT WOS:000368049900007
PM 25806565
ER
PT J
AU Tamura, RN
Krischer, JP
Pagnoux, C
Micheletti, R
Grayson, PC
Chen, YF
Merkel, PA
AF Tamura, Roy N.
Krischer, Jeffrey P.
Pagnoux, Christian
Micheletti, Robert
Grayson, Peter C.
Chen, Yeh-Fong
Merkel, Peter A.
TI A small n sequential multiple assignment randomized trial design for use
in rare disease research
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Re-randomization; Binary data; Weighted Z statistic
ID CLINICAL-TRIALS; TREATMENT STRATEGIES
AB Background: Clinical trials in rare diseases are difficult to conduct due to the limited number of patients available with each disorder. We developed a Phase 2 trial which is a small n sequential multiple assignment randomized trial (snSMART) design to test several treatments for a rare disease for which no standard therapy exists.
Purpose: This paper illustrates the design, sample size estimation and operating characteristics of an snSMART.
Methods: We investigate the performance of a class of weighted Z statistics via computer simulations.
Results: We demonstrate the increase in power over traditional single stage designs, and indicate how the power changes as a function of the weight given to each stage.
Conclusion: The snSMART design is promising in a rare disease setting where several alternative treatments are under consideration and small sample sizes are necessary. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Tamura, Roy N.; Krischer, Jeffrey P.] Univ S Florida, Hlth Informat Inst, Tampa, FL 33612 USA.
[Pagnoux, Christian] Univ Toronto, Dept Rheumatol, Toronto, ON M5S 1A1, Canada.
[Micheletti, Robert] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA.
[Micheletti, Robert] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Grayson, Peter C.] Natl Inst Arthrit & Musculoskeletal Dis, Syst Autoimmun Branch, Bethesda, MD USA.
[Chen, Yeh-Fong] US FDA, Div Biometr 3, Off Biostat, Silver Spring, MD USA.
[Merkel, Peter A.] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA.
RP Tamura, RN (reprint author), Univ S Florida, Hlth Informat Inst, 3650 Spectrum Blvd, Tampa, FL 33612 USA.
EM roy.tamura@epi.usf.edu; jeffrey.krischer@epi.usf.edu;
Cpagnoux@mtsinia.on.ca; Robert.Micheletti@uphs.upenn.edu;
peter.grayson@nih.gov; YehFong.Chen@fda.hhs.gov;
Peter.Merkel@uphs.upenn.edu
RI Pagnoux, Christian/C-4612-2015
FU Vasculitis Clinical Research Consortium (VCRC), Rare Diseases Clinical
Research Network (RDCRN) [U54 AR057319, U01 AR51874 04]; Office of Rare
Diseases Research (ORDR); NCATS; National Institute of Arthritis and
Musculoskeletal and Skin Diseases (NIAMS); National Center for Research
Resources [U54 RR019497]; Data Management and Coordinating Center,
(DMCC) [U01 TR001263]; RDCRN; National Center for Advancing
Translational Science (NCATS)
FX The Vasculitis Clinical Research Consortium (VCRC) (U54 AR057319 and U01
AR51874 04) is part of the Rare Diseases Clinical Research Network
(RDCRN), an initiative of the Office of Rare Diseases Research (ORDR),
National Center for Advancing Translational Science (NCATS). The VCRC is
funded through collaboration between NCATS, and the National Institute
of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and has
received funding from the National Center for Research Resources (U54
RR019497). The Data Management and Coordinating Center, (DMCC) (U01
TR001263) housed at the Health Informatics Institute, is part of the
RDCRN and is funded through NCATS.
NR 13
TC 3
Z9 3
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
EI 1559-2030
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD JAN
PY 2016
VL 46
BP 48
EP 51
DI 10.1016/j.cct.2015.11.010
PG 4
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA DB0NH
UT WOS:000368204300008
PM 26586608
ER
PT J
AU Reddy, SP
Wang, H
Adams, JK
Feng, PCH
AF Reddy, Shanker P.
Wang, Hua
Adams, Jennifer K.
Feng, Peter C. H.
TI Prevalence and Characteristics of Salmonella Serotypes Isolated from
Fresh Produce Marketed in the United States
SO JOURNAL OF FOOD PROTECTION
LA English
DT Article
ID ESCHERICHIA-COLI STRAINS; MICROBIOLOGICAL QUALITY; GROUND-BEEF;
MICROBIAL-CONTAMINATION; LISTERIA-MONOCYTOGENES; RESISTANT SALMONELLA;
FOOD COMMODITIES; RETAIL MARKETS; TOMATO PLANTS; RISK-FACTORS
AB Salmonella continues to rank as one of the most costly foodborne pathogens, and more illnesses are now associated with the consumption of fresh produce. The U.S. Department of Agriculture Microbiological Data Program (MDP) sampled select commodities of fresh fruit and vegetables and tested them for Salmonella, pathogenic Escherichia coli, and Listeria. The Salmonella strains isolated were further characterized by serotype, antimicrobial resistance, and pulsed-field gel electrophoresis profile. This article summarizes the Salmonella data collected by the MDP between 2002 and 2012. The results show that the rates of Salmonella prevalence ranged from absent to 0.34% in cilantro. A total of 152 isolates consisting of over 50 different serotypes were isolated from the various produce types, and the top five were Salmonella enterica serotype Cubana, S. enterica subspecies arizonae (subsp. IIIa) and diarizonae (subsp. IIIb), and S. enterica serotypes Newport, Javiana, and Infantis. Among these, Salmonella serotypes Newport and Javiana are also listed among the top five Salmonella serotypes that caused most foodborne outbreaks. Other serotypes that are frequent causes of infection, such as S. enterica serotypes Typhimurium and Enteritidis, were also found in fresh produce but were not prevalent. About 25% of the MDP samples were imported produce, including 65% of green onions, 44% of tomatoes, 42% of hot peppers, and 41% of cantaloupes. However, imported produce did not show higher numbers of Salmonella-positive samples, and in some products, like cilantro, all of the Salmonella isolates were from domestic samples. About 6.5% of the Salmonella isolates were resistant to the antimicrobial compounds tested, but no single commodity or serotype was found to be the most common carrier of resistant strains or of resistance. The pulsed-field gel electrophoresis profiles of the produce isolates showed similarities with Salmonella isolates from meat samples and from outbreaks, but there were also profile diversities among the strains within some serotypes, like Salmonella Newport.
C1 [Reddy, Shanker P.] USDA, Agr Mkt Serv, Washington, DC 20250 USA.
[Wang, Hua; Feng, Peter C. H.] US FDA, Div Microbiol, College Pk, MD 20740 USA.
[Adams, Jennifer K.] Assoc Publ Hlth Labs, Silver Spring, MD 20910 USA.
RP Feng, PCH (reprint author), US FDA, Div Microbiol, College Pk, MD 20740 USA.
EM peter.feng@fda.hhs.gov
NR 61
TC 1
Z9 1
U1 1
U2 19
PU INT ASSOC FOOD PROTECTION
PI DES MOINES
PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA
SN 0362-028X
EI 1944-9097
J9 J FOOD PROTECT
JI J. Food Prot.
PD JAN
PY 2016
VL 79
IS 1
BP 6
EP 16
DI 10.4315/0362-028X.JFP-15-274
PG 11
WC Biotechnology & Applied Microbiology; Food Science & Technology
SC Biotechnology & Applied Microbiology; Food Science & Technology
GA DA7DQ
UT WOS:000367965200002
PM 26735024
ER
PT J
AU Ding, HL
Fu, TJ
AF Ding, Hongliu
Fu, Tong-Jen
TI Assessing the Public Health Impact and Effectiveness of Interventions To
Prevent Salmonella Contamination of Sprouts
SO JOURNAL OF FOOD PROTECTION
LA English
DT Article
ID QUANTITATIVE RISK-ASSESSMENT; ESCHERICHIA-COLI O157H7; MICROBIAL RISK;
LISTERIA-MONOCYTOGENES; CONSUMPTION; GROWTH; SEED
AB Sprouts have been a recurring public health challenge due to microbiological contamination, and Salmonella has been the major cause of sprout-associated outbreaks. Although seed treatment and microbiological testing have been applied as risk reduction measures during sprout production, the extent to which their effectiveness in reducing the public health risks associated with sprouts has not been well investigated. We conducted a quantitative risk assessment to measure the risk posed by Salmonella contamination in sprouts and to determine whether and how mitigation strategies can achieve a satisfactory risk reduction based on the assumption that the risk reduction achieved by a microbiological sampling and testing program at a given sensitivity is equivalent to that achieved by direct inactivation of pathogens. Our results indicated that if the sprouts were produced without any risk interventions, the health impact caused by sprouts contaminated with Salmonella would be very high, with a median annual estimated loss of disability-adjusted life years (DALYs) of 691,412. Seed treatment (with 20,000 ppm of calcium hypochlorite) or microbiological sampling and testing of spent irrigation water (SIW) alone could reduce the median annual impact to 734 or 4,856 DALYs, respectively. Combining seed treatment with testing of the SIW would further decrease the risk to 58 DALYs. This number could be dramatically lowered to 3.99 DALYs if sprouts were produced under conditions that included treating seeds with 20,000 ppm of calcium hypochlorite plus microbiological testing of seeds, SIW, and finished products. Our analysis shows that the public health impact due to Salmonella contamination in sprouts could be controlled if seeds are treated to reduce pathogens and microbiological sampling and testing is implemented. Future advances in intervention strategies would be important to improve sprout safety further.
C1 [Ding, Hongliu; Fu, Tong-Jen] US FDA, Div Food Proc Sci & Technol, Bedford Pk, IL 60501 USA.
RP Ding, HL (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Epidemiol, 20903 New Hampshire Ave, Silver Spring, MD 20993 USA.
FU U.S. Food and Drug Administration (FDA) Commissioner's Fellowship
Program; FDA Center for Food Safety and Applied Nutrition; Oak Ridge
Institute for Science Education
FX This work was supported by the U.S. Food and Drug Administration (FDA)
Commissioner's Fellowship Program and by a contract by the FDA Center
for Food Safety and Applied Nutrition with the Oak Ridge Institute for
Science Education. We thank Dr. Mary Lou Tortorello and Dr. Michelle
Smith for their review of this manuscript.
NR 32
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U1 4
U2 7
PU INT ASSOC FOOD PROTECTION
PI DES MOINES
PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA
SN 0362-028X
EI 1944-9097
J9 J FOOD PROTECT
JI J. Food Prot.
PD JAN
PY 2016
VL 79
IS 1
BP 37
EP 42
DI 10.4315/0362-028X.JFP-15-184
PG 6
WC Biotechnology & Applied Microbiology; Food Science & Technology
SC Biotechnology & Applied Microbiology; Food Science & Technology
GA DA7DQ
UT WOS:000367965200005
PM 26735027
ER
PT J
AU Jester, ELE
Loader, JI
El Said, KR
Abraham, A
Quintana, HAF
Plakas, SM
AF Jester, Edward L. E.
Loader, Jared I.
El Said, Kathleen R.
Abraham, Ann
Quintana, Harold A. Flores
Plakas, Steven M.
TI Performance Assessment and Comparability of a Commercial Enzyme-Linked
Immunosorbent Assay Kit with Liquid Chromatography Tandem Mass
Spectrometry for Chloramphenicol Residues in Crab and Shrimp
SO JOURNAL OF FOOD PROTECTION
LA English
DT Article
ID MEDICATED-FEED; TROUT; CONFIRMATION; ELIMINATION; ELISA; MEAT
AB Monitoring for chloramphenicol (CAP) in aquaculture products is primarily performed by liquid chromatography tandem mass spectrometry (LC-MS/MS), which requires expensive equipment and specialized training. Many laboratories prefer to screen samples with facile and high-throughput enzyme-linked immunosorbent assay (ELISA) kits for CAP residues before submitting samples for LC-MS/MS quantification and confirmation. We evaluated the performance of a Ridascreen (R-Biopharm) ELISA kit for CAP in spiked and incurred crab and shrimp muscle at levels bracketing the minimum required performance level for analysis (0.3 ng/g). The Ridascreen ELISA kit incorporates antibody directed against CAP. Incurred CAP levels in crab and shrimp muscle were verified using LC-MS/MS. We found good repeatability (relative standard deviation) of the ELISA in spiked and incurred crab and shrimp muscle samples, with values ranging from 6.8 to 21.7%. Recoveries of CAP from tissues spiked at 0.15 to 0.60 ng/g ranged from 102 to 107%. Minimal cross-reactivity with blank crab and shrimp muscle matrix components was observed. ELISA data were highly correlated with those of LC-MS/MS for CAP in incurred muscle tissue. We believe this study to be the first evaluation of the performance and comparability of a CAP ELISA kit and LC-MS/MS for determination of CAP residues, as well as their elimination, in crab muscle. Our findings support the use of this ELISA kit for screening purposes and, when used in conjunction with validated instrumental methods, for regulatory monitoring of CAP in these species.
C1 [Jester, Edward L. E.; Loader, Jared I.; El Said, Kathleen R.; Abraham, Ann; Quintana, Harold A. Flores; Plakas, Steven M.] US FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA.
RP Jester, ELE (reprint author), US FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA.
EM Edward.Jester@FDA.HHS.GOV
NR 15
TC 0
Z9 0
U1 2
U2 10
PU INT ASSOC FOOD PROTECTION
PI DES MOINES
PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA
SN 0362-028X
EI 1944-9097
J9 J FOOD PROTECT
JI J. Food Prot.
PD JAN
PY 2016
VL 79
IS 1
BP 117
EP 122
DI 10.4315/0362-028X.JFP-15-380
PG 6
WC Biotechnology & Applied Microbiology; Food Science & Technology
SC Biotechnology & Applied Microbiology; Food Science & Technology
GA DA7DQ
UT WOS:000367965200015
PM 26735037
ER
PT J
AU Boonmuen, N
Gong, P
Ali, Z
Chittiboyina, AG
Khan, I
Doerge, DR
Helferich, WG
Carlson, KE
Martin, T
Piyachaturawat, P
Katzenellenbogen, JA
Katzenellenbogen, BS
AF Boonmuen, Nittaya
Gong, Ping
Ali, Zulfiqar
Chittiboyina, Amar G.
Khan, Ikhlas
Doerge, Daniel R.
Helferich, William G.
Carlson, Kathryn E.
Martin, Teresa
Piyachaturawat, Pawinee
Katzenellenbogen, John A.
Katzenellenbogen, Benita S.
TI Licorice root components in dietary supplements are selective estrogen
receptor modulators with a spectrum of estrogenic and anti-estrogenic
activities
SO STEROIDS
LA English
DT Article
DE Estrogen receptor; Selective estrogen receptor modulator; Botanical
estrogens; Licorice root estrogens
ID GENE-EXPRESSION; HUMAN-DISEASE; HOT FLASHES; BINDING; CELLS; LIGAND;
BETA; COREGULATORS; STABILITY; NUCLEAR
AB Licorice root extracts are often consumed as botanical dietary supplements by menopausal women as a natural alternative to pharmaceutical hormone replacement therapy. In addition to their components liquiritigenin (Liq) and isoliquiritigenin (Iso-Liq), known to have estrogenic activity, licorice root extracts also contain a number of other flavonoids, isoflavonoids, and chalcones. We have investigated the estrogenic activity of 7 of these components, obtained from an extract of Glycyrrhiza glabra powder, namely Glabridin (L1), Calycosin (L2), Methoxychalcone (L3), Vestitol (L4), Glyasperin C (L5), Glycycoumarin (L6), and Glicoricone (L7), and compared them with Liq, Iso-Liq, and estradiol (E2). All components, including Liq and Iso-Liq, have low binding affinity for estrogen receptors (ERs). Their potency and efficacy in stimulating the expression of estrogen-regulated genes reveal that Liq and Iso-Liq and L2,13, L4, and L6 are estrogen agonists. Interestingly, 13 and L4 have an efficacy nearly equivalent to E2 but with a potency ca. 10,000-fold less. The other components, L1, L5 and L7, acted as partial estrogen antagonists. All agonist activities were reversed by the antiestrogen, ICI 182,780, or by knockdown of ER alpha with siRNA, indicating that they are ER dependent. In HepG2 hepatoma cells stably expressing ER alpha, only Liq, 'so-Lig, and L3 stimulated estrogen-regulated gene expression, and in all cases gene stimulation did not occur in HepG2 cells lacking ER alpha. Collectively, these findings classify the components of licorice root extracts as low potency, mixed ER agonists and antagonists, having a character akin to that of selective estrogen receptor modulators or SERMs. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Boonmuen, Nittaya; Gong, Ping; Katzenellenbogen, Benita S.] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA.
[Boonmuen, Nittaya; Piyachaturawat, Pawinee] Mahidol Univ, Dept Physiol, Fac Sci, Bangkok 10400, Thailand.
[Ali, Zulfiqar; Chittiboyina, Amar G.; Khan, Ikhlas] Univ Mississippi, Natl Ctr Nat Prod Res, Oxford, MS 38677 USA.
[Doerge, Daniel R.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Helferich, William G.] Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA.
[Carlson, Kathryn E.; Martin, Teresa; Katzenellenbogen, John A.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
[Piyachaturawat, Pawinee] Mahidol Univ, Chakri Naruebodindra Med Inst, Ramathibodi Hosp, Fac Med, Bangkok 10400, Thailand.
RP Katzenellenbogen, BS (reprint author), Univ Illinois, Dept Mol & Integrat Physiol, 524 Burrill Hall,407 South Goodwin Ave, Urbana, IL 61801 USA.
EM katzenel@illinois.edu
FU NIH from the National Center for Complementary and Integrative Health
(NCCIH) [P50AT006268]; Thailand Research Fund through the Royal Golden
Jubilee Ph.D. Program [PHD/0170/2552]; NIH [DK015556]
FX This study was made possible by NIH Grant Number P50AT006268 (to WGH,
IK, DD, JAK and BSK) from the National Center for Complementary and
Integrative Health (NCCIH), the Office of Dietary Supplements (ODS) and
the National Cancer Institute (NCI). Financial support from the Thailand
Research Fund through the Royal Golden Jubilee Ph.D. Program (Grant No.
PHD/0170/2552) to PP and NB, and from NIH DK015556 (to JAK) is
gratefully acknowledged. The contents of this manuscript are solely the
responsibility of the authors and do not necessarily represent the
official views of the NCCIH, ODS, NCI, the National Institutes of
Health, or the U.S. Food and Drug Administration.
NR 29
TC 7
Z9 7
U1 3
U2 17
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-128X
EI 1878-5867
J9 STEROIDS
JI Steroids
PD JAN
PY 2016
VL 105
BP 42
EP 49
DI 10.1016/j.steroids.2015.11.006
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA DB0TH
UT WOS:000368219900005
PM 26631549
ER
PT J
AU Skripchenko, A
Gelderman, MP
Awatefe, H
Turgeon, A
Thompson-Montgomery, D
Cheng, C
Vostal, JG
Wagner, SJ
AF Skripchenko, Andrey
Gelderman, Monique P.
Awatefe, Helen
Turgeon, Annette
Thompson-Montgomery, Dedeene
Cheng, Chunrong
Vostal, Jaroslav G.
Wagner, Stephen J.
TI Automated cold temperature cycling improves in vitro platelet properties
and in vivo recovery in a mouse model compared to continuous cold
storage
SO TRANSFUSION
LA English
DT Article
ID 4 DEGREES-C; STORED PLATELETS; APHERESIS PLATELETS; SURVIVAL;
AGGREGATION; TRANSFUSION; MAINTENANCE; VIABILITY; 22-DEGREES-C;
CONCENTRATE
AB BACKGROUNDPlatelets (PLTs) stored at cold temperatures (CTs) for prolonged time have dramatically reduced bacterial growth but poor survival when infused. A previous study demonstrated that human PLTs stored with manual cycling between 4 degrees C (12 hr) and 37 degrees C (30 min) and infused into severe combined immunodeficient (SCID) mice had survivals similar to or greater than those stored at room temperature (RT). In this study, the in vitro and in vivo properties of PLTs stored in an automated incubator programmed to cycle between 5 degrees C (11 hr) and 37 degrees C (1 hr) were evaluated.
STUDY DESIGN AND METHODSA Trima apheresis unit (n=12) was aliquoted (60 mL) in CLX bags. One sample was stored with continuous agitation (RT), a second sample was stored at 4-6 degrees C without agitation (CT), and a third sample was placed in an automated temperature cycler with 5 minutes of agitation during the warm-up period (thermocycling [TC]). PLTs were assayed for several relevant quality variables. On Day 7, PLTs were infused into SCID mice and in vivo recovery was assessed at predetermined time points after transfusion.
RESULTSThe glucose consumption rate, morphology score, hypotonic shock recovery level, and aggregation levels were increased and mitochondrial reactive oxygen species accumulations were decreased in TC-PLTs compared to those of CT-PLTs. The pH and Annexin V binding were comparable to those of RT-PLTs. All TC-PLTs had greater recovery than CT-PLTs and were comparable to RT-PLTs.
CONCLUSIONPLTs stored under automated TC conditions have improved in vivo recovery and improved results for a number of in vitro measures compared to CT-PLTs.
C1 [Skripchenko, Andrey; Awatefe, Helen; Turgeon, Annette; Thompson-Montgomery, Dedeene; Wagner, Stephen J.] Amer Red Cross, Holland Lab, Biomed Serv, Rockville, MD 20855 USA.
[Gelderman, Monique P.; Vostal, Jaroslav G.] FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Silver Spring, MD USA.
[Cheng, Chunrong] Ctr Biol Evaluat & Res CBER, Off Biostatist & Epidemiol, FDA, Silver Spring, MD USA.
RP Skripchenko, A (reprint author), Amer Red Cross, 15601 Crabbs Branch Way, Rockville, MD 20855 USA.
EM Andrey.skripchenko@redcross.org
NR 27
TC 5
Z9 5
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD JAN
PY 2016
VL 56
IS 1
BP 24
EP 32
DI 10.1111/trf.13273
PG 9
WC Hematology
SC Hematology
GA DA6YJ
UT WOS:000367951500004
PM 26331697
ER
PT J
AU De Groote, H
Narrod, C
Kimenju, SC
Bett, C
Scott, RPB
Tiongco, MM
Gitonga, ZM
AF De Groote, Hugo
Narrod, Clare
Kimenju, Simon C.
Bett, Charles
Scott, Rosemarie P. B.
Tiongco, Marites M.
Gitonga, Zachary M.
TI Measuring rural consumers' willingness to pay for quality labels using
experimental auctions: the case of aflatoxin-free maize in Kenya
SO AGRICULTURAL ECONOMICS
LA English
DT Article
DE Aflatoxins; Maize; Kenya; Willingness to pay; Consumers; Rural
ID GENETICALLY-MODIFIED FOOD; INFORMATION; CHOICE; CONTAMINATION; MARKET
AB Aflatoxins are a common health hazard in tropical countries, especially in rural areas. New methods to reduce aflatoxin levels in food staples, as well as cheaper test methods, are being developed, but consumers' willingness to pay (WTP) for these improvements is unknown. A survey was conducted with a representative sample of rural consumers (1,344 in total, 63% women) in all major maize-production zones of Kenya. The survey included an experimental auction with maize products of different qualities. The results showed that many rural consumers were aware of aflatoxins, but few understood their health risks. Respondents were willing to pay a premium for maize tested for aflatoxins and labeled, but asked a high discount for maize that was visibly contaminated with moldy grain. The premium was higher for respondents with education and in regions with aflatoxicosis outbreaks. Knowledge of aflatoxins substantially reduced the overall WTP, but did not increase the WTP for tested maize. Welfare analysis indicates that mandatory testing would result in substantial benefits if the cost of testing can be lowered to below the premium.
C1 [De Groote, Hugo; Kimenju, Simon C.; Gitonga, Zachary M.] Int Maize & Wheat Improvement Ctr CIMMYT, Nairobi 00621, Kenya.
[Narrod, Clare] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA.
[Bett, Charles] Kenya Agr & Livestock Res Org, Arid & Rangelands Res Inst, KALRO Katumani Res Ctr, Machakos, Kenya.
[Scott, Rosemarie P. B.; Tiongco, Marites M.] Int Food Policy Res Inst, Washington, DC 20006 USA.
RP De Groote, H (reprint author), Int Maize & Wheat Improvement Ctr CIMMYT, POB 1041, Nairobi 00621, Kenya.
EM h.degroote@cgiar.org
FU Bill and Melinda Gates Foundation under Aflacontrol Project
FX We thank the Bill and Melinda Gates Foundation for their support under
the Aflacontrol Project, the enumerators and supervisors for their
dedication in the field, the farmers for their time, the CIMMYT staff
for the logistic support, the Provincial Administration officers for
helping us with the sampling frame, Menale Kassie for checking the
formulas, and Kathleen Sinclair for editing.
NR 37
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U1 5
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0169-5150
EI 1574-0862
J9 AGR ECON-BLACKWELL
JI Agric. Econ.
PD JAN
PY 2016
VL 47
IS 1
BP 33
EP 45
DI 10.1111/agec.12207
PG 13
WC Agricultural Economics & Policy; Economics
SC Agriculture; Business & Economics
GA DA2YH
UT WOS:000367662600003
ER
PT J
AU Holland, GN
Eydelman, MB
Cunningham, B
Chambers, WA
AF Holland, Gary N.
Eydelman, Malvina B.
Cunningham, Brad
Chambers, Wiley A.
TI Food and Drug Administration Procedures for New Drug and Device
Approvals
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Editorial Material
C1 [Holland, Gary N.] Univ Calif Los Angeles, Stein Eye Inst, Ocular Inflammatory Dis Ctr, Los Angeles, CA 90095 USA.
[Holland, Gary N.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
[Eydelman, Malvina B.; Cunningham, Brad] US FDA, Div Ophthalm & Ear Nose & Throat Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Chambers, Wiley A.] US FDA, Div Transplant & Ophthalmol Prod, Off Antimicrobial Prod, Off New Drugs,Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Holland, GN (reprint author), Univ Calif Los Angeles, Stein Eye Inst, 100 Stein Plaza, Los Angeles, CA 90095 USA.
EM uveitis@jsei.ucla.edu
NR 3
TC 0
Z9 0
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD JAN
PY 2016
VL 161
BP 1
EP 3
DI 10.1016/j.ajo.2015.11.022
PG 3
WC Ophthalmology
SC Ophthalmology
GA DA2NG
UT WOS:000367632300001
PM 26699740
ER
PT J
AU Varadhan, R
Wang, SJ
AF Varadhan, Ravi
Wang, Sue-Jane
TI Treatment effect heterogeneity for univariate subgroups in clinical
trials: Shrinkage, standardization, or else
SO BIOMETRICAL JOURNAL
LA English
DT Article
DE Bayesian shrinkage estimate; Confounding; Empirical Bayes; Marginal
subgroup analysis; Maximum likelihood estimate; Naive estimate;
Standardization; Subgroup analysis
AB Treatment effect heterogeneity is a well-recognized phenomenon in randomized controlled clinical trials. In this paper, we discuss subgroup analyses with prespecified subgroups of clinical or biological importance. We explore various alternatives to the naive (the traditional univariate) subgroup analyses to address the issues of multiplicity and confounding. Specifically, we consider a model-based Bayesian shrinkage (Bayes-DS) and a nonparametric, empirical Bayes shrinkage approach (Emp-Bayes) to temper the optimism of traditional univariate subgroup analyses; a standardization approach (standardization) that accounts for correlation between baseline covariates; and a model-based maximum likelihood estimation (MLE) approach. The Bayes-DS and Emp-Bayes methods model the variation in subgroup-specific treatment effect rather than testing the null hypothesis of no difference between subgroups. The standardization approach addresses the issue of confounding in subgroup analyses. The MLE approach is considered only for comparison in simulation studies as the "truth" since the data were generated from the same model. Using the characteristics of a hypothetical large outcome trial, we perform simulation studies and articulate the utilities and potential limitations of these estimators. Simulation results indicate that Bayes-DS and Emp-Bayes can protect against optimism present in the naive approach. Due to its simplicity, the naive approach should be the reference for reporting univariate subgroup-specific treatment effect estimates from exploratory subgroup analyses. Standardization, although it tends to have a larger variance, is suggested when it is important to address the confounding of univariate subgroup effects due to correlation between baseline covariates. The Bayes-DS approach is available as an R package (DSBayes).
C1 [Varadhan, Ravi] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Div Biostat & Bioinformat, Baltimore, MD USA.
[Varadhan, Ravi] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
[Wang, Sue-Jane] FDA, Off Biostat, OTS, CDER, Silver Spring, MD 20993 USA.
[Wang, Sue-Jane] Johns Hopkins Univ, Engn & Appl Sci Programs Profess, Baltimore, MD USA.
RP Wang, SJ (reprint author), FDA, Off Biostat, OTS, CDER, Silver Spring, MD 20993 USA.
EM suejane.wang@fda.hhs.gov
FU Patient-Centered Outcomes Research Institute (PCORI) [ME-1303-5896]
FX We wish to thank Prof. Dieter Hauschke and Dr. Claudia Schmoor for their
kind invitation. The first author (R.V.) would like to acknowledge the
funding from the contract provided by the Patient-Centered Outcomes
Research Institute (PCORI) under contract ME-1303-5896.
NR 10
TC 2
Z9 2
U1 2
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0323-3847
EI 1521-4036
J9 BIOMETRICAL J
JI Biom. J.
PD JAN
PY 2016
VL 58
IS 1
SI SI
BP 133
EP 153
DI 10.1002/bimj.201400102
PG 21
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA DA3WN
UT WOS:000367731300009
PM 26485117
ER
PT J
AU Lathrop, JT
Jeffery, DA
Shea, YR
Scholl, PF
Chan, MM
AF Lathrop, Julia Tait
Jeffery, Douglas A.
Shea, Yvonne R.
Scholl, Peter F.
Chan, Maria M.
TI US Food and Drug Administration Perspectives on Clinical Mass
Spectrometry
SO CLINICAL CHEMISTRY
LA English
DT Article
ID MULTIPLEX ASSAYS; DIAGNOSTICS; PROTEOMICS; PROTEINS
AB Mass spectrometry based in vitro diagnostic devices that measure proteins and peptides are underutilized in clinical practice, and none has been cleared or approved by the Food and Drug Administration (FDA) for marketing or for use in clinical trials. One way to increase their utilization is through enhanced interactions between the FDA and the clinical mass spectrometry community to improve the validation and regulatory review of these devices. As a reference point from which to develop these interactions, this article surveys the FDA's regulation of mass spectrometry based devices, explains how the FDA uses guidance documents and standards in the review process, and describes the FDA's previous outreach to stakeholders. Here we also discuss how further communication and collaboration with the clinical mass spectrometry communities can identify opportunities for the FDA to provide help in the development of mass spectrometry based devices and enhance their entry into the clinic. (C) 2015 American Association for Clinical Chemistry
C1 [Lathrop, Julia Tait; Jeffery, Douglas A.; Chan, Maria M.] US FDA, Div Hematol & Immunol Devices, Silver Spring, MD USA.
[Shea, Yvonne R.] US FDA, Div Microbiol Devices, Silver Spring, MD USA.
[Shea, Yvonne R.] US FDA, Off Vitro Diagnost & Radiol Hlth, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Scholl, Peter F.] US FDA, Div Analyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, Silver Spring, MD USA.
[Chan, Maria M.] US FDA, Silver Spring, MD USA.
RP Lathrop, JT (reprint author), OIR CDRH FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM julia.lathrop@fda.hhs.gov
OI Scholl, Peter/0000-0002-8870-3266
NR 25
TC 4
Z9 4
U1 1
U2 9
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
EI 1530-8561
J9 CLIN CHEM
JI Clin. Chem.
PD JAN
PY 2016
VL 62
IS 1
BP 41
EP 47
DI 10.1373/clinchem.2015.244731
PG 7
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA DA3NC
UT WOS:000367703400012
PM 26553791
ER
PT J
AU Rajaraman, P
Doody, MM
Yu, CL
Preston, DL
Miller, JS
Sigurdson, AJ
Freedman, DM
Alexander, BH
Little, MP
Miller, DL
Linet, MS
AF Rajaraman, Preetha
Doody, Michele M.
Yu, Chu Ling
Preston, Dale L.
Miller, Jeremy S.
Sigurdson, Alice J.
Freedman, D. Michal
Alexander, Bruce H.
Little, Mark P.
Miller, Donald L.
Linet, Martha S.
TI Incidence and mortality risks for circulatory diseases in US radiologic
technologists who worked with fluoroscopically guided interventional
procedures, 1994-2008
SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
ID CARDIOLOGY PROCEDURES; RADIATION RISKS; EXPOSURE; STROKE
AB Objectives Although fluoroscopically guided interventional procedures (FGIP) have provided major advances in the treatment of various common diseases, radiation exposures associated with these procedures may cause adverse health effects in workers. We assess risk of circulatory disease incidence and mortality in medical radiation workers performing FGIP.
Methods A US nationwide prospective cohort study of 90957 radiologic technologists who completed a cohort survey during 1994-1998 was followed until completion of a subsequent survey during 2003-2005 for circulatory disease incidence, or until 31 December 2008 for mortality. Incidence analyses were restricted to the 63482 technologists who completed both the second survey (1994-1998) and the third survey (2003-2005). Cox proportional hazards models were used to assess adjusted HR and 95% CIs for mortality from all causes, all circulatory diseases, all heart diseases, ischaemic heart disease, stroke, acute myocardial infarction and hypertension in participants who reported ever performing FGIP compared to technologists who never performed FGIP procedures. Adjusted HRs were calculated for self-reported hypertension, stroke and myocardial infarction.
Results We observed a 34% increase in stroke incidence (HR=1.34, 95% CI 1.10 to 1.64) in technologists who performed FGIP compared to those who never performed these procedures. Mortality from stroke was also modestly elevated, although not statistically significant (HR=1.22, 95% CI 0.85 to 1.73). We observed no statistically significant excess risks of incidence or mortality from any other outcome evaluated.
Conclusions Our finding of elevated risk of stroke in workers performing FGIP needs to be confirmed in studies with individual radiation dose data, but nonetheless underlines the need to keep radiation exposure as low as reasonably achievable without compromising key diagnostic information.
C1 [Rajaraman, Preetha; Doody, Michele M.; Sigurdson, Alice J.; Freedman, D. Michal; Little, Mark P.; Linet, Martha S.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
[Rajaraman, Preetha] NCI, Ctr Global Hlth, NIH, DHHS, Bethesda, MD 20892 USA.
[Yu, Chu Ling] Kaiser Permanente, Mid Atlantic Permanente Res Inst, Rockville, MD USA.
[Preston, Dale L.] HiroSoft Int Corp, Seattle, WA USA.
[Miller, Jeremy S.] Informat Management Syst Inc, Calverton, MD USA.
[Alexander, Bruce H.] Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, Minneapolis, MN USA.
[Miller, Donald L.] Food & Drug Adm, Ctr Devices & Radiol Hlth, Off In Vitro Diagnost & Radiol Hlth, Silver Spring, MD USA.
RP Rajaraman, P (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM rajarama@mail.nih.gov
OI Little, Mark/0000-0003-0980-7567
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health, Department of Health and Human Services,
USA
FX The research was funded by the intramural programme of the Division of
Cancer Epidemiology and Genetics, National Cancer Institute, National
Institutes of Health, Department of Health and Human Services, USA.
NR 20
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Z9 3
U1 0
U2 5
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1351-0711
EI 1470-7926
J9 OCCUP ENVIRON MED
JI Occup. Environ. Med.
PD JAN
PY 2016
VL 73
IS 1
BP 21
EP 27
DI 10.1136/oemed-2015-102888
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DA6BH
UT WOS:000367886200004
PM 26350678
ER
PT J
AU Kovacs, SM
Turner-Bowker, DM
Calarco, G
Mulberg, AE
Paty, J
AF Kovacs, Sarrit M.
Turner-Bowker, Diane M.
Calarco, Gina
Mulberg, Andrew E.
Paty, Jean
TI Practical Considerations for the Use of Clinical Outcome Assessments
(COAs) in Pediatric Clinical Research: Examples From Pediatric
Gastroenterology
SO THERAPEUTIC INNOVATION & REGULATORY SCIENCE
LA English
DT Article
DE patient-reported outcome (PRO); functional constipation; clinical trial;
drug development; gastroesophageal
ID TASK-FORCE; PRO INSTRUMENTS; VALIDITY; CHILDREN; FDA
AB Clinical outcome assessments (COAs), including patient-reported outcome (PRO) measures, are routinely used in drug development and other clinical research initiatives to assess the impact of treatment on patient health and well-being. The FDA Guidance for Industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims (2009), the European Medicines Agency's Reflection Paper on the Regulatory Guidance for the Use of Health-Related Quality of Life Measures in the Evaluation of Medicinal Products (2005), and the International Society for Pharmacoeconomics and Outcomes Research PRO Good Research Practices for the Assessment of Children and Adolescence Task Force (2013) outline key considerations and good measurement principles that are relevant to the selection and use of COAs in a pediatric population. However, challenges remain in the appropriate selection and use of COAs to assess treatment benefit in pediatric clinical research. The purpose of this paper is to summarize proceedings from a panel presentation at the Critical Path Institute's 2015 Annual PRO Consortium Workshop. This paper underscores the importance of considering children's specific needs and the numerous challenges faced when developing and implementing well-defined and reliable COAs in pediatric clinical trials evaluating medical products, and describes some approaches to addressing these unique needs and challenges.
C1 [Kovacs, Sarrit M.; Mulberg, Andrew E.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Turner-Bowker, Diane M.] Adelphi Values, Adelphi, MD USA.
[Calarco, Gina] Quintiles, Pediat Ctr Excellence, Kansas City, MO USA.
[Paty, Jean] Quintiles, Advisory Serv, New York, NY USA.
RP Kovacs, SM (reprint author), 10903 New Hampshire Ave,Bldg 22, Silver Spring, MD 20993 USA.
EM Sarrit.Kovacs@fda.hhs.gov
FU Sucampo Pharma Americas LLC; Takeda Pharmaceutical Company Limited
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: Sucampo
Pharma Americas LLC and Takeda Pharmaceutical Company Limited sponsored
the research presented as the case study in pediatric functional
constipation.
NR 10
TC 0
Z9 0
U1 1
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 2168-4790
EI 2168-4804
J9 THER INNOV REGUL SCI
JI Ther. Innov. Regul. Sci.
PD JAN
PY 2016
VL 50
IS 1
BP 37
EP 43
DI 10.1177/2168479015621601
PG 7
WC Medical Informatics; Pharmacology & Pharmacy
SC Medical Informatics; Pharmacology & Pharmacy
GA DA5IW
UT WOS:000367837800006
ER
PT J
AU Luan, JJ
Mani, R
Hung, HMJ
AF Luan, Jingyu Julia
Mani, Ranjit
Hung, H. M. James
TI Comparison of Treatment Effects Between US and Non-US Study Sites in
Multiregional Alzheimer Disease Clinical Trials
SO THERAPEUTIC INNOVATION & REGULATORY SCIENCE
LA English
DT Article
DE multiregional clinical trials; Alzheimer disease; treatment effect;
analysis of covariance (ANCOVA); forest plot
ID PUBLICATION BIAS; CONSISTENCY; DESIGN; REGIONS
AB Background: Conducting clinical trials across multiple regions of the world has become common practice. A multiregional clinical trial (MRCT) presents opportunities as well as challenges. However, regional differences of treatment effects appear in many MRCTs, which make the interpretation of clinical trial results difficult and presents challenges for clinical trial design. Alzheimer disease (AD) is a progressive neurodegenerative disorder that affects approximately 5 million people in the United States and is the sixth leading cause of death in the country. In 2014, AD cost the United States $214 billion, and the cost is expected to rise to $1.2 trillion by 2050.
Methods: In this article, we utilize data from New Drug Applications (NDAs) that have been approved for the treatment of AD to study whether there are differences in treatment effect between US and non-US study sites. Using an analysis of covariance (ANCOVA) model and forest plot, we analyze the treatment difference by region (US and non-US) from 3 separate perspectives: by region for each trial, by region for each endpoint, and by region and trial for each endpoint.
Results: Overall, the analyses indicate that treatment effects in clinical trials for AD are generally in the expected direction in both US and non-US sites. There was no clear evidence of heterogeneity in treatment effects between US and non-US sites.
Conclusions: It appears that there is no clear evidence to suggest that MRCTs should not be used to study AD.
C1 [Luan, Jingyu Julia] US FDA, Div Biometr 8, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Mani, Ranjit] US FDA, Div Neurol Prod, Off Drug Evaluat 1, Off New Drugs,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Hung, H. M. James] US FDA, Div Biometr 1, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Luan, JJ (reprint author), US FDA, Div Biometr 8, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 21,Room 4669, Silver Spring, MD 20993 USA.
EM Jingyu.Luan@fda.hhs.gov
NR 10
TC 0
Z9 0
U1 1
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 2168-4790
EI 2168-4804
J9 THER INNOV REGUL SCI
JI Ther. Innov. Regul. Sci.
PD JAN
PY 2016
VL 50
IS 1
BP 66
EP 73
DI 10.1177/2168479015611629
PG 8
WC Medical Informatics; Pharmacology & Pharmacy
SC Medical Informatics; Pharmacology & Pharmacy
GA DA5IW
UT WOS:000367837800010
ER
PT J
AU Aminololama-Shakeri, S
Abbey, CK
Gazi, P
Prionas, ND
Nosratieh, A
Li, CS
Boone, JM
Lindfors, KK
AF Aminololama-Shakeri, Shadi
Abbey, Craig K.
Gazi, Peymon
Prionas, Nicolas D.
Nosratieh, Anita
Li, Chin-Shang
Boone, John M.
Lindfors, Karen K.
TI Differentiation of ductal carcinoma in-situ from benign
micro-calcifications by dedicated breast computed tomography
SO EUROPEAN JOURNAL OF RADIOLOGY
LA English
DT Article
DE Contrast enhanced breast CT; Breast CT; DCIS; Micro calcifications;
Ductal carcinoma in situ
ID ENHANCED DIGITAL MAMMOGRAPHY; INITIAL CLINICAL-EXPERIENCE;
DORFMAN-BERBAUM-METZ; SCREENING MAMMOGRAPHY; CT; PERFORMANCE; READERS;
LESIONS; COST; ROC
AB Purpose: Compare conspicuity of ductal carcinoma in-situ (DCIS) to benign calcifications on unenhanced (bCT), contrast-enhanced dedicated breast CT (CEbCT) and mammography (DM).
Methods and materials: The institutional review board approved this HIPAA-compliant study. 42 women with Breast Imaging Reporting and Data System 4 or 5 category micro-calcifications had breast CT before biopsy. Three subjects with invasive disease at surgery were excluded. Two breast radiologists independently compared lesion conspicuity scores (CS) for CEbCT, to bCT and DM. Enhancement was measured in Hounsfield units (HU). Mean CS +/- standard deviations are shown. Receiver operating characteristic analysis (ROC) measured radiologists' discrimination performance by comparing CS to enhancement alone. Statistical measurements were made using ANOVA F-test, Wilcoxon rank-sum test and robust linear regression analyses.
Results: 39 lesions (17 DCIS, 22 benign) were analyzed. DCIS (8.5 +/- 0.9, n=17) was more conspicuous than benign micro-calcifications (3.6 +/- 2.9, n=22; p <0.0001) on CEbCT. DCIS was equally conspicuous on CEbCT and DM (8.5 +/- 0.9, 8.7 +/- 0.8, n=17; p=0.85) and more conspicuous when compared to bCT (5.3 +/- 2.6, n=17; p < 0.001). All DCIS enhanced; mean enhancement (90HU +/- 53HU, n=17) was higher compared to benign lesions (33 +/- 30HU, n=22) (p < 0.0001). ROC analysis of the radiologists' CS showed high discrimination performance (AUC = 0.94) compared to enhancement alone (AUC = 0.85) (p< 0.026).
Conclusion: DCIS is more conspicuous than benign micro-calcifications on CEbCT. DCIS visualization on CEbCT is equal to mammography but improved compared to bCT. Radiologists' discrimination performance using CEBCT is significantly higher than enhancement values alone. CEbCT may have an advantage over mammography by reducing false positive examinations when calcifications are analyzed. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Aminololama-Shakeri, Shadi; Gazi, Peymon; Prionas, Nicolas D.; Boone, John M.; Lindfors, Karen K.] Univ Calif Davis, Med Ctr, Dept Radiol, Sacramento, CA 95817 USA.
[Li, Chin-Shang] Univ Calif Davis, Dept Publ Hlth Sci, Div Biostat, Davis, CA 95616 USA.
[Abbey, Craig K.] Univ Calif Santa Barbara, Dept Psychol & Brain Sci, Santa Barbara, CA 93106 USA.
[Nosratieh, Anita] US FDA, Ctr Devices & Radiol Heath, Washington, DC 20204 USA.
RP Aminololama-Shakeri, S (reprint author), Univ Calif Davis, Med Ctr, Dept Radiol, 4860 Y St,Suite 3100, Sacramento, CA 95817 USA.
EM sshakeri@ucdavis.edu
OI Prionas, Nicolas/0000-0001-5067-7077
FU National Institutes of Health (NIH) [R01 EB002138, R21-EB018939];
National Center for Research Resources (NCRR) of the National Institutes
of Health (NIH) [UL1 RR024146]; NIH Roadmap for Medical Research
FX The project described was supported by the National Institutes of Health
(NIH), through grants # R01 EB002138 and R21-EB018939. Statistical
support for this publication was made possible by Grant Number UL1
RR024146 from the National Center for Research Resources (NCRR), a
component of the National Institutes of Health (NIH), and NIH Roadmap
for Medical Research.
NR 25
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Z9 2
U1 2
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0720-048X
EI 1872-7727
J9 EUR J RADIOL
JI Eur. J. Radiol.
PD JAN
PY 2016
VL 85
IS 1
BP 297
EP 303
DI 10.1016/j.ejrad.2015.09.020
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CZ8OA
UT WOS:000367357800040
PM 26520874
ER
PT J
AU Fermini, B
Hancox, JC
Abi-Gerges, N
Bridgland-Taylor, M
Chaudhary, KW
Colatsky, T
Correll, K
Crumb, W
Damiano, B
Erdemli, G
Gintant, G
Imredy, J
Koerner, J
Kramer, J
Levesque, P
Li, ZH
Lindqvist, A
Obejero-Paz, CA
Rampe, D
Sawada, K
Strauss, DG
Vandenberg, JI
AF Fermini, Bernard
Hancox, Jules C.
Abi-Gerges, Najah
Bridgland-Taylor, Matthew
Chaudhary, Khuram W.
Colatsky, Thomas
Correll, Krystle
Crumb, William
Damiano, Bruce
Erdemli, Gul
Gintant, Gary
Imredy, John
Koerner, John
Kramer, James
Levesque, Paul
Li, Zhihua
Lindqvist, Anders
Obejero-Paz, Carlos A.
Rampe, David
Sawada, Kohei
Strauss, David G.
Vandenberg, Jamie I.
TI A New Perspective in the Field of Cardiac Safety Testing through the
Comprehensive In Vitro Proarrhythmia Assay Paradigm
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Review
DE CiPA; Comprehensive In Vitro Proarrhythmic Assay; hERG; ICH E14; ICH
S7B; QT interval; safety
ID CELL-DERIVED CARDIOMYOCYTES; QT INTERVAL PROLONGATION;
TORSADES-DE-POINTES; PLURIPOTENT STEM-CELLS; HERG POTASSIUM CHANNEL;
DRUG DISCOVERY; REPOLARIZATION; RISK; PHARMACOLOGY; BLOCK
AB For the past decade, cardiac safety screening to evaluate the propensity of drugs to produce QT interval prolongation and Torsades de Pointes (TdP) arrhythmia has been conducted according to ICH S7B and ICH E14 guidelines. Central to the existing approach are hERG channel assays and in vivo QT measurements. Although effective, the present paradigm carries a risk of unnecessary compound attrition and high cost, especially when considering costly thorough QT (TQT) studies conducted later in drug development. The Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative is a public-private collaboration with the aim of updating the existing cardiac safety testing paradigm to better evaluate arrhythmia risk and remove the need for TQT studies. It is hoped that CiPA will produce a standardized ion channel assay approach, incorporating defined tests against major cardiac ion channels, the results of which then inform evaluation of proarrhythmic actions in silico, using human ventricular action potential reconstructions. Results are then to be confirmed using human (stem cell-derived) cardiomyocytes. This perspective article reviews the rationale, progress of, and challenges for the CiPA initiative, if this new paradigm is to replace existing practice and, in time, lead to improved and widely accepted cardiac safety testing guidelines.
C1 [Fermini, Bernard] Pfizer Inc, Global Safety Pharmacol, Groton, CT 06340 USA.
[Hancox, Jules C.] Univ Bristol, Sch Physiol & Pharmacol, Bristol, Avon, England.
[Abi-Gerges, Najah] AstraZeneca R&D, Drug Safety & Metab, Innovat Med & Early Dev, Translat Safety, Macclesfield, Cheshire, England.
[Bridgland-Taylor, Matthew] AstraZeneca R&D, Innovat Med & Early Dev, Discovery Sci, Macclesfield, Cheshire, England.
[Chaudhary, Khuram W.] GlaxoSmithKline, Safety Assessment, King Of Prussia, PA USA.
[Colatsky, Thomas; Li, Zhihua] US FDA, CDER, Div Appl Regulatory Sci, Silver Spring, MD USA.
[Correll, Krystle] Safety Pharmacol Soc, Reston, VA USA.
[Crumb, William] Zenas Technol LLC, New Orleans, LA USA.
[Damiano, Bruce] Janssen Res & Dev LLC, Discovery Sci, Global Safety Pharmacol, Spring House, PA USA.
[Erdemli, Gul] Novartis Inst BioMed Res Inc, Ctr Prote Chem, Cambridge, MA USA.
[Gintant, Gary] AbbVie, Integrated Sci & Technol, Dept Integrat Pharmacol, N Chicago, IL USA.
[Imredy, John] Merck & Co Inc, Dept Safety Assessment, Kenilworth, NJ USA.
[Koerner, John] US FDA, CDER, Div Cardiovasc & Renal Prod, Silver Spring, MD USA.
[Kramer, James; Obejero-Paz, Carlos A.] ChanTest, Cleveland, OH USA.
[Levesque, Paul] Bristol Myers Squibb Co, Res & Dev, Princeton, NJ USA.
[Lindqvist, Anders] Biolin Sci, Ballerup, Denmark.
[Rampe, David] Sanofi, Preclin Safety, Bridgewater, NJ USA.
[Sawada, Kohei] Eisai & Co Ltd, Global Cardiovasc Assessment, Ibaraki, Japan.
[Strauss, David G.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Vandenberg, Jamie I.] Univ NSW, St Vincents Clin Sch, Victor Chang Cardiac Res Inst, Darlinghurst, NSW, Australia.
RP Fermini, B (reprint author), Pfizer Inc, Global Safety Pharmacol, MS8274-1347 Eastern Point Rd, Groton, CT 06340 USA.
EM Bernard.fermini@pfizer.com
OI Fermini, Bernard/0000-0003-1040-401X; Vandenberg,
Jamie/0000-0002-3859-3716
NR 50
TC 35
Z9 35
U1 1
U2 6
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
EI 1552-454X
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD JAN
PY 2016
VL 21
IS 1
BP 1
EP 11
DI 10.1177/1087057115594589
PG 11
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry
GA CZ7WD
UT WOS:000367310100001
PM 26170255
ER
PT J
AU Walters, KA
D'Agnillo, F
Sheng, ZM
Kindrachuk, J
Schwartzman, LM
Kuestner, RE
Chertow, DS
Golding, BT
Taubenberger, JK
Kash, JC
AF Walters, Kathie-Anne
D'Agnillo, Felice
Sheng, Zong-Mei
Kindrachuk, Jason
Schwartzman, Louis M.
Kuestner, Rolf E.
Chertow, Daniel S.
Golding, Basil T.
Taubenberger, Jeffery K.
Kash, John C.
TI 1918 pandemic influenza virus and Streptococcus pneumoniae co-infection
results in activation of coagulation and widespread pulmonary thrombosis
in mice and humans
SO JOURNAL OF PATHOLOGY
LA English
DT Article
DE 1918 influenza; Streptococcus pneumoniae; co-infection; inflammation;
extrinsic pathway of coagulation; pulmonary thrombosis
ID NEUTROPHIL EXTRACELLULAR TRAPS; BACTERIAL PNEUMONIA; IMMUNE-RESPONSE;
HOST IMMUNE; INFECTION; PATHOGENESIS; LUNG; NETS; PATHOGENICITY;
NEURAMINIDASE
AB To study bacterial co-infection following 1918 H1N1 influenza virus infection, mice were inoculated with the 1918 influenza virus, followed by Streptococcus pneumoniae (SP) 72 h later. Co-infected mice exhibited markedly more severe disease, shortened survival time and more severe lung pathology, including widespread thrombi. Transcriptional profiling revealed activation of coagulation only in co-infected mice, consistent with the extensive thrombogenesis observed. Immunohistochemistry showed extensive expression of tissue factor (F3) and prominent deposition of neutrophil elastase on endothelial and epithelial cells in co-infected mice. Lung sections of SP-positive 1918 autopsy cases showed extensive thrombi and prominent staining for F3 in alveolar macrophages, monocytes, neutrophils, endothelial and epithelial cells, in contrast to co-infection-positive 2009 pandemic H1N1 autopsy cases. This study reveals that a distinctive feature of 1918 influenza virus and SP co-infection in mice and humans is extensive expression of tissue factor and activation of the extrinsic coagulation pathway leading to widespread pulmonary thrombosis. Copyright (c) 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
C1 [Walters, Kathie-Anne; Kuestner, Rolf E.] Inst Syst Biol, Seattle, WA USA.
[D'Agnillo, Felice; Golding, Basil T.] US FDA, Lab Biochem & Vasc Biol, Div Hematol Res & Review, Ctr Biol Evaluat & Res,Off Blood Res & Review, Silver Spring, MD USA.
[Kindrachuk, Jason; Chertow, Daniel S.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Sheng, Zong-Mei; Schwartzman, Louis M.; Chertow, Daniel S.; Taubenberger, Jeffery K.; Kash, John C.] NIAID, NIH, Infect Dis Lab, Viral Pathogenesis & Evolut Sect, Bethesda, MD 20892 USA.
RP Taubenberger, JK (reprint author), NIAID, NIH, Infect Dis Lab, 33 North Dr,MSC 3203, Bethesda, MD 20892 USA.
EM taubenbergerj@niaid.nih.gov; kashj@niaid.nih.gov
OI Kindrachuk, Jason/0000-0002-3305-7084
FU Intramural Research Programmes of the National Institutes of Health
(NIH); National Institute of Allergy and Infectious Diseases (NIAID);
Defense Threat Reduction Agency [HDTRA-1-08-C-0023]
FX This study was supported by the Intramural Research Programmes of the
National Institutes of Health (NIH) and the National Institute of
Allergy and Infectious Diseases (NIAID). KAW and REK were supported by
the Defense Threat Reduction Agency (Contract No. HDTRA-1-08-C-0023). We
thank Dr David Morens at NIAID/NIH for helpful discussions. Animal care
was performed by the Comparative Medicine Branch, NIH/NIAID.
NR 38
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U1 3
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3417
EI 1096-9896
J9 J PATHOL
JI J. Pathol.
PD JAN
PY 2016
VL 238
IS 1
BP 85
EP 97
DI 10.1002/path.4638
PG 13
WC Oncology; Pathology
SC Oncology; Pathology
GA CZ7QW
UT WOS:000367295800010
PM 26383585
ER
PT J
AU Parr, A
Hidalgo, IJ
Bode, C
Brown, W
Yazdanian, M
Gonzalez, MA
Sagawa, K
Miller, K
Jiang, WL
Stippler, ES
AF Parr, Alan
Hidalgo, Ismael J.
Bode, Chris
Brown, William
Yazdanian, Mehran
Gonzalez, Mario A.
Sagawa, Kazuko
Miller, Kevin
Jiang, Wenlei
Stippler, Erika S.
TI The Effect of Excipients on the Permeability of BCS Class III Compounds
and Implications for Biowaivers
SO PHARMACEUTICAL RESEARCH
LA English
DT Article
DE BCS class III; bioavailability; Caco-2; permeability; rat intestinal
perfusion model
ID ORAL DOSAGE FORMS; BIOPHARMACEUTICS CLASSIFICATION-SYSTEM;
POLYETHYLENE-GLYCOL 400; DRUG ABSORPTION; CACO-2 CELLS; THEORETICAL
BASIS; MONOGRAPHS; BIOAVAILABILITY; PHARMACOKINETICS; SOLUBILITY
AB Currently, the FDA allows biowaivers for Class I (high solubility and high permeability) and Class III (high solubility and low permeability) compounds of the Biopharmaceutics Classification System (BCS). Scientific evidence should be provided to support biowaivers for BCS Class I and Class III (high solubility and low permeability) compounds.
Data on the effects of excipients on drug permeability are needed to demonstrate that commonly used excipients do not affect the permeability of BCS Class III compounds, which would support the application of biowaivers to Class III compounds. This study was designed to generate such data by assessing the permeability of four BCS Class III compounds and one Class I compound in the presence and absence of five commonly used excipients.
The permeability of each of the compounds was assessed, at three to five concentrations, with each excipient in two different models: Caco-2 cell monolayers, and in situ rat intestinal perfusion. No substantial increases in the permeability of any of the compounds were observed in the presence of any of the tested excipients in either of the models, with the exception of disruption of Caco-2 cell monolayer integrity by sodium lauryl sulfate at 0.1 mg/ml and higher.
The results suggest that the absorption of these four BCS Class III compounds would not be greatly affected by the tested excipients. This may have implications in supporting biowaivers for BCS Class III compounds in general.
C1 [Parr, Alan; Miller, Kevin] GlaxoSmithKline Inc, Res Triangle Pk, NC 27709 USA.
[Hidalgo, Ismael J.; Bode, Chris] Absorpt Syst LP, Exton, PA 19341 USA.
[Brown, William; Stippler, Erika S.] US Pharmacopeial Convent Inc, Rockville, MD 20852 USA.
[Yazdanian, Mehran] Teva Branded Pharmaceut R&D Inc, W Chester, PA 19380 USA.
[Gonzalez, Mario A.] PKinetics Int Inc, Pembroke Pines, FL 33027 USA.
[Sagawa, Kazuko] Pfizer Global Res & Dev, Groton, CT 06340 USA.
[Jiang, Wenlei] US FDA, Off Gener Drugs, Silver Spring, MD 20841 USA.
RP Bode, C (reprint author), Absorpt Syst LP, Exton, PA 19341 USA.
EM cbode@absorption.com
FU Product Quality Research Institute (PQRI); Absorption Systems
FX The authors extend special thanks to the Product Quality Research
Institute (PQRI) and Absorption Systems for their financial support of
this work and declare no potential conflicts of interest.
NR 38
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PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0724-8741
EI 1573-904X
J9 PHARM RES-DORDR
JI Pharm. Res.
PD JAN
PY 2016
VL 33
IS 1
BP 167
EP 176
DI 10.1007/s11095-015-1773-4
PG 10
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA CZ8II
UT WOS:000367343000013
PM 26286187
ER
PT J
AU Zeitler, EP
Al-Khatib, SM
Drozda, JP
Kessler, LG
Kirtane, AJ
Kong, DF
Laschinger, J
Marinac-Dabic, D
Morice, MC
Reed, T
Sedrakyan, A
Stein, KM
Tcheng, J
Krucoff, MW
AF Zeitler, Emily P.
Al-Khatib, Sana M.
Drozda, Joseph P., Jr.
Kessler, Larry G.
Kirtane, Ajay J.
Kong, David F.
Laschinger, John
Marinac-Dabic, Danica
Morice, Marie-Claude
Reed, Terrie
Sedrakyan, Art
Stein, Kenneth M.
Tcheng, James
Krucoff, Mitchell W.
TI Predictable and Su Stainable Implementation of National Cardiovascular
Registries (PASSION) infrastructure: A think tank report from Medical
Device Epidemiological Network Initiative (MDEpiNet)
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID ACADEMIC RESEARCH CONSORTIUM; LEARNING HEALTH-CARE; CLINICAL-TRIALS;
INFORMED-CONSENT; DEFINITIONS; MULTICENTER; SOCIETY; ETHICS; SAFETY;
FOOD
AB The MDEpiNet is a public-private partnership between the US Food and Drug Administration's Center for Devices and Radiological Health and participating partners. The PASSION program is an MDEpiNet-sponsored program that aims to demonstrate the goals of MDEpiNet by using cardiovascular medical device registries to bridge evidence gaps across the medical device total product life cycle. To this end, a PASSION Think Tank meeting took place in October 201 4 in Silver Spring, MD, to facilitate discussion between stakeholders about the successes, challenges, and future novel applications of medical device registries, with particular emphasis on identifying pilot projects. Participants spanned a broad range of groups including patients, device manufacturers, regulators, physicians/academicians, professional societies, providers, and payers. The meeting focus included 4 areas of cardiovascular medicine intended to cultivate interest in 4 MDEpiNet disease-specific/device-specific working groups: coronary intervention, electrophysiology, valvular disease, and peripheral vascular disease. In addition, more general issues applying to registry-based infrastructure and analytical methodologies for assessing device benefit/risk were considered to provide context for the working groups as PASSION programs going forward. This article summarizes the discussions at the meeting and the future directions of the PASSION program.
C1 [Zeitler, Emily P.; Al-Khatib, Sana M.; Kong, David F.; Tcheng, James; Krucoff, Mitchell W.] Duke Clin Res Inst, Durham, NC USA.
[Drozda, Joseph P., Jr.] Mercy Hlth, Chesterfield, MO USA.
[Kessler, Larry G.] Univ Washington, Seattle, WA 98195 USA.
[Kirtane, Ajay J.] Columbia Univ, Herbert & Sandi Feinberg Intervent Cardiol & Hear, Med Ctr, New York Presbyterian Hosp, New York, NY USA.
[Kirtane, Ajay J.] Cardiovasc Res Fdn, New York, NY USA.
[Laschinger, John; Marinac-Dabic, Danica; Reed, Terrie] US FDA, Silver Spring, MD USA.
[Morice, Marie-Claude] European Cardiovasc Res Ctr, Massy, France.
[Sedrakyan, Art] Weill Cornell Med Coll, New York, NY USA.
[Stein, Kenneth M.] Boston Sci, St Paul, MN USA.
RP Krucoff, MW (reprint author), Duke Univ, Med Ctr, 2400 Pratt St, Durham, NC 27705 USA.
EM mitchell.krucoff@duke.edu
FU NHLBI NIH HHS [T32 HL069749]
NR 34
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U1 1
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
EI 1097-5330
J9 AM HEART J
JI Am. Heart J.
PD JAN
PY 2016
VL 171
IS 1
BP 64
EP 72
DI 10.1016/j.ahj.42015.07.029
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CZ5EV
UT WOS:000367126200009
PM 26699602
ER
PT J
AU Restrepo, BJ
Rieger, M
AF Restrepo, Brandon J.
Rieger, Matthias
TI Denmark's Policy on Artificial Trans Fat and Cardiovascular Disease
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID CORONARY-HEART-DISEASE; STROKE REGARDS COHORT; RACIAL-DIFFERENCES;
ACIDS; MORTALITY; REASONS; HEALTH; RISK; FOOD
AB Introduction: The consumption of trans fat is associated with cardiovascular disease (CVD). In January 2004, Denmark became the first country in the world to regulate the content of artificial trans fat in certain ingredients in food products, which nearly eliminated artificial trans fat from the Danish food supply. The goal of this study was to assess whether Denmark's trans fat policy reduced deaths caused by CVD.
Methods: Annual mortality rates in Organisation for Economic Co-operation and Development (OECD) countries from 1990 to 2012 were used to estimate the effect of Denmark's food policy on CVD mortality rates. Synthetic control methods were employed to simulate the CVD mortality trajectory that Denmark would have witnessed in the absence of the policy and to measure the policy's impact on CVD mortality rates. Analyses were conducted in 2015.
Results: Before the trans fat policy was implemented, CVD mortality rates in Denmark closely tracked those of a weighted average of other OECD countries (i.e., the synthetic control group). In the years before the policy, the annual mean was 441.5 deaths per 100,000 people in Denmark and 442.7 in the synthetic control group. In the 3 years after the policy was implemented, mortality attributable to CVD decreased on average by about 14.2 deaths per 100,000 people per year in Denmark relative to the synthetic control group.
Conclusions: Denmark's food policy, which restricted the content of artificial trans fat in certain ingredients in its food supply, has been followed by a decrease in CVD mortality rates. Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine
C1 [Restrepo, Brandon J.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
[Rieger, Matthias] Erasmus Univ, Inst Social Studies, The Hague, Netherlands.
RP Restrepo, BJ (reprint author), 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM brandon.restrepo@eui.eu
NR 24
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Z9 6
U1 1
U2 17
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD JAN
PY 2016
VL 50
IS 1
BP 69
EP 76
DI 10.1016/j.amepre.2015.06.018
PG 8
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA CZ1DF
UT WOS:000366845300014
PM 26319518
ER
PT J
AU Schill, KM
Wang, Y
Butler, RR
Pombert, JF
Reddy, NR
Skinner, GE
Larkin, JW
AF Schill, Kristin M.
Wang, Yun
Butler, Robert R., III
Pombert, Jean-Francois
Reddy, N. Rukma
Skinner, Guy E.
Larkin, John W.
TI Genetic Diversity of Clostridium sporogenes PA 3679 Isolates Obtained
from Different Sources as Resolved by Pulsed-Field Gel Electrophoresis
and High-Throughput Sequencing
SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY
LA English
DT Article
ID BOTULINUM TYPE-A; TANDEM-REPEAT ANALYSIS; HEAT-RESISTANCE;
HIGH-PRESSURE; GROUP-I; SPORULATION TEMPERATURE; GENOME SEQUENCE; B
BOTULINUS; SPORES; STRAINS
AB Clostridium sporogenes PA 3679 is a nonpathogenic, nontoxic model organism for proteolytic Clostridium botulinum used in the validation of conventional thermal food processes due to its ability to produce highly heat-resistant endospores. Because of its public safety importance, the uncertain taxonomic classification and genetic diversity of PA 3679 are concerns. Therefore, isolates of C. sporogenes PA 3679 were obtained from various sources and characterized using pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing. The phylogenetic relatedness and genetic variability were assessed based on 16S rRNA gene sequencing and whole-genome single nucleotide polymorphism (SNP) analysis. All C. sporogenes PA 3679 isolates were categorized into two clades (clade I containing ATCC 7955 NCA3679 isolates 1961-2, 1990, and 2007 and clade II containing PA 3679 isolates NFL, UW, FDA, and Campbell and ATCC 7955 NCA3679 isolate 1961-4). The 16S maximum likelihood (ML) tree clustered both clades within proteolytic C. botulinum strains, with clade I forming a distinct cluster with other C. sporogenes non-PA 3679 strains. SNP analysis revealed that clade I isolates were more similar to the genomic reference PA 3679 (NCTC8594) genome (GenBank accession number AGAH00000000.1) than clade II isolates were. The genomic reference C. sporogenes PA 3679 (NCTC8594) genome and clade I C. sporogenes isolates were genetically distinct from those obtained from other sources (University of Wisconsin, National Food Laboratory, U.S. Food and Drug Administration, and Campbell's Soup Company). Thermal destruction studies revealed that clade I isolates were more sensitive to high temperature than clade II isolates were. Considering the widespread use of C. sporogenes PA 3679 and its genetic information in numerous studies, the accurate identification and genetic characterization of C. sporogenes PA 3679 are of critical importance.
C1 [Schill, Kristin M.; Wang, Yun; Reddy, N. Rukma; Skinner, Guy E.; Larkin, John W.] US FDA, Ctr Food Safety & Appl Nutr, Bedford Pk, IL 60501 USA.
[Butler, Robert R., III; Pombert, Jean-Francois] IIT, Dept Biol, Chicago, IL 60616 USA.
RP Schill, KM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Bedford Pk, IL 60501 USA.
EM Kristin.Schill@fda.hhs.gov; jpombert@iit.edu
RI Wang, Yun/G-8899-2016;
OI Pombert, Jean-Francois/0000-0002-3449-8375; Butler,
Robert/0000-0003-0200-8682
FU U.S. Department of Energy; FDA
FX Y.W. was supported by an appointment to the Research Participation
Program at the Center for Food Safety and Applied Nutrition administered
by the Oak Ridge Institute for Science and Education via an inter-agency
agreement between the U.S. Department of Energy and the FDA. The sponsor
had no role in the study design, data collection and analysis, the
decision to publish, or the preparation of the manuscript.
NR 57
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U1 3
U2 14
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0099-2240
EI 1098-5336
J9 APPL ENVIRON MICROB
JI Appl. Environ. Microbiol.
PD JAN
PY 2016
VL 82
IS 1
BP 384
EP 393
DI 10.1128/AEM.02616-15
PG 10
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA CZ1UO
UT WOS:000366891200038
PM 26519392
ER
PT J
AU Newsome, GA
Ackerman, LK
Johnson, KJ
AF Newsome, G. Asher
Ackerman, Luke K.
Johnson, Kevin J.
TI Humidity Effects on Fragmentation in Plasma-Based Ambient Ionization
Sources
SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
LA English
DT Article
DE Humidity; FAPA; DART; Ambient ionization; Water cluster; Mechanism;
Fragmentation
ID PRESSURE CHEMICAL-IONIZATION; DESORPTION/IONIZATION MASS-SPECTROMETRY;
HEXAMETHYLENE TRIPEROXIDE DIAMINE; DIELECTRIC BARRIER DISCHARGE;
ION-SOURCE; PROBE; SENSITIVITY; AFTERGLOW; AIR
AB Post-plasma ambient desorption/ionization (ADI) sources are fundamentally dependent on surrounding water vapor to produce protonated analyte ions. There are two reports of humidity effects on ADI spectra. However, it is unclear whether humidity will affect all ADI sources and analytes, and by what mechanism humidity affects spectra. Flowing atmospheric pressure afterglow (FAPA) ionization and direct analysis in real time (DART) mass spectra of various surface-deposited and gas-phase analytes were acquired at ambient temperature and pressure across a range of observed humidity values. A controlled humidity enclosure around the ion source and mass spectrometer inlet was used to create programmed humidity and temperatures. The relative abundance and fragmentation of molecular adduct ions for several compounds consistently varied with changing ambient humidity and also were controlled with the humidity enclosure. For several compounds, increasing humidity decreased protonated molecule and other molecular adduct ion fragmentation in both FAPA and DART spectra. For others, humidity increased fragment ion ratios. The effects of humidity on molecular adduct ion fragmentation were caused by changes in the relative abundances of different reagent protonated water clusters and, thus, a change in the average difference in proton affinity between an analyte and the population of water clusters. Control of humidity in ambient post-plasma ion sources is needed to create spectral stability and reproducibility.
C1 [Newsome, G. Asher] Nova Res Inc, Alexandria, VA 22308 USA.
[Ackerman, Luke K.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Analyt Chem, College Pk, MD 20740 USA.
[Johnson, Kevin J.] US Naval Res Lab, Naval Tech Ctr Safety & Survivabil, Washington, DC 20375 USA.
RP Newsome, GA (reprint author), Nova Res Inc, 1900 Elkin St Suite 230, Alexandria, VA 22308 USA.
EM graham.newsome.ctr@nrl.navy.mil
RI Ackerman, Luke/E-4597-2011; Newsome, G. Asher/J-8970-2012
OI Ackerman, Luke/0000-0001-6626-3039; Newsome, G.
Asher/0000-0003-1683-2197
FU Office of Naval Research (ONR) through the Naval Research Laboratory's
Basic Research Program
FX The authors thank Michael Malito of Nova Research, Inc. for assistance
designing the source enclosure; the Gary M. Hieftje lab of Indiana
University for providing the FAPA source; Jon Wong of the FDA Center for
Food Safety and Applied Nutrition for providing propazine; and Lauryn
DeGreeff-Silk of the Naval Research Laboratory for preparing the HMTD
solution. Funding for this project was provided by the Office of Naval
Research (ONR) through the Naval Research Laboratory's Basic Research
Program.
NR 30
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U1 7
U2 26
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1044-0305
EI 1879-1123
J9 J AM SOC MASS SPECTR
JI J. Am. Soc. Mass Spectrom.
PD JAN
PY 2016
VL 27
IS 1
BP 135
EP 143
DI 10.1007/s13361-015-1259-y
PG 9
WC Biochemical Research Methods; Chemistry, Analytical; Chemistry,
Physical; Spectroscopy
SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy
GA CZ3OW
UT WOS:000367014900015
PM 26384684
ER
PT J
AU Jiang, LL
Fantoni, G
Couzens, L
Gao, J
Plant, E
Ye, ZP
Eichelberger, MC
Wan, HQ
AF Jiang, Lianlian
Fantoni, Giovanna
Couzens, Laura
Gao, Jin
Plant, Ewan
Ye, Zhiping
Eichelberger, Maryna C.
Wan, Hongquan
TI Comparative Efficacy of Monoclonal Antibodies That Bind to Different
Epitopes of the 2009 Pandemic H1N1 Influenza Virus Neuraminidase
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID A VIRUS; OSELTAMIVIR-RESISTANT; HEMAGGLUTININ; VACCINE; IMMUNIZATION;
REPLICATION; INHIBITION; PROTECTION; MECHANISM; INFECTION
AB Antibodies against the neuraminidase (NA) of influenza virus correlate with resistance against disease, but the effectiveness of antibodies against different NA epitopes has not been compared. In the present study, we evaluated the in vitro and in vivo efficacies of four monoclonal antibodies (MAbs): HF5 and CD6, which are specific to two different epitopes in the NA of 2009 pandemic H1N1 (pH1N1) virus, and 4E9 and 1H5, which are specific to a conserved epitope in the NA of both H1N1 and H5N1 viruses. In the in vitro assays, HF5 and CD6 inhibited virus spread and growth more effectively than 4E9 and 1H5, with HF5 being the most effective inhibitor. When administered prophylactically at 5 mg/kg of body weight, HF5 and CD6 protected similar to 90 to 100% of DBA/2 mice against lethal wild-type pH1N1 virus challenge; however, at a lower dose (1 mg/kg), HF5 protected similar to 90% of mice, whereas CD6 protected only 25% of mice. 4E9 and 1H5 were less effective than HF5 and CD6, as indicated by the partial protection achieved even at doses as high as 15 mg/kg. When administered therapeutically, HF5 protected a greater proportion of mice against lethal pH1N1 challenge than CD6. However, HF5 quickly selected pH1N1 virus escape mutants in both prophylactic and therapeutic treatments, while CD6 did not. Our findings confirm the important role of NA-specific antibodies in immunity to influenza virus and provide insight into the properties of NA antibodies that may serve as good candidates for therapeutics against influenza.
C1 [Jiang, Lianlian; Fantoni, Giovanna; Couzens, Laura; Gao, Jin; Plant, Ewan; Ye, Zhiping; Eichelberger, Maryna C.; Wan, Hongquan] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
RP Eichelberger, MC (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
EM maryna.eichelberger@fda.hhs.gov; hongquan.wan@fda.hhs.gov
OI Plant, Ewan/0000-0003-0166-5939
FU FDA
FX This work was supported by intramural FDA funds. L.J. and G.F. were
supported by training funds administered by the Oak Ridge Institute for
Science and Education.
NR 39
TC 1
Z9 1
U1 2
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JAN
PY 2016
VL 90
IS 1
BP 117
EP 128
DI 10.1128/JVI.01756-15
PG 12
WC Virology
SC Virology
GA CZ1XK
UT WOS:000366899000012
PM 26468531
ER
PT J
AU Major, ME
AF Major, Marian E.
TI Hepatitis C: new clues to better vaccines?
SO GUT
LA English
DT Editorial Material
ID VIRUS-INFECTION; PROTECTION; IMMUNITY
C1 [Major, Marian E.] US FDA, Lab Hepatitis Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
RP Major, ME (reprint author), US FDA, Lab Hepatitis Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
EM marian.major@fda.hhs.gov
NR 10
TC 0
Z9 0
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
EI 1468-3288
J9 GUT
JI Gut
PD JAN
PY 2016
VL 65
IS 1
BP 4
EP 5
DI 10.1136/gutjnl-2015-309829
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CY4TE
UT WOS:000366400500003
PM 26092844
ER
PT B
AU Fox, WF
Murray, M
AF Fox, William F.
Murray, Matthew
BE Frank, J
MartinezVazquez, J
TI The challenge of operating and maintaining infrastructure
SO DECENTRALIZATION AND INFRASTRUCTURE IN THE GLOBAL ECONOMY: FROM GAPS TO
SOLUTIONS
SE Routledge Studies in the Modern World Economy
LA English
DT Article; Book Chapter
ID MAINTENANCE
C1 [Fox, William F.] Goethe Univ Frankfurt, Amer Studies, Frankfurt, Germany.
[Murray, Matthew] Univ Tennessee, CBER, Knoxville, TN USA.
[Murray, Matthew] Univ Tennessee, Dept Econ, Knoxville, TN USA.
[Murray, Matthew] CBER, London, England.
[Murray, Matthew] Howard H Baker Jr Ctr Publ Policy, Knoxville, TN USA.
[Murray, Matthew] Ball Corp, Knoxville, TN USA.
[Murray, Matthew] Coll Business Adm, Business, New York, NY USA.
[Murray, Matthew] Publ Adm Major Econ, Washington, DC USA.
RP Fox, WF (reprint author), Fed Reserve Bank, Kansas City, MO 64198 USA.
NR 14
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U1 0
U2 0
PU ROUTLEDGE
PI ABINGDON
PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND
BN 978-1-315-69410-8; 978-1-138-90920-5
J9 ROUTL STUD MOD WORLD
PY 2016
VL 143
BP 305
EP 323
PG 19
WC Economics
SC Business & Economics
GA BD8JT
UT WOS:000364009100011
ER
PT J
AU Eischeid, AC
AF Eischeid, Anne C.
TI Development and evaluation of a real-time PCR assay for detection of
lobster, a crustacean shellfish allergen
SO FOOD CONTROL
LA English
DT Article
DE Quantitative PCR; Mitochondrial 12S gene; Food allergen; Reaction
efficiency; Autoclave; Boil
ID POLYMERASE-CHAIN-REACTION; PROCESSED FOODS; DNA; HEAT; PRESSURE; SHRIMP
AB Crustacean shellfish are a leading cause of food allergy in American adults, and the Food Allergen Labeling and Consumer Protection Act requires that different types of crustacean shellfish be distinguished from each other. In general ELISA assays are not capable of differentiating crustacean type, but PCR assays are. In this work, a real-time PCR assay for lobster, a crustacean shellfish allergen, was developed and evaluated. Food matrices were spiked with lobster meat at 0.1, 1, 10, 100, 1000, 10(4), and 10(5) parts per million (ppm). In addition to testing of several different food matrices, method performance was determined using conditions which have historically proven challenging for PCR analyses, specifically food matrices with low DNA content and acidic pH levels, as well as foods that were treated with combined high temperature and pressure. Real-time PCR standard curves were generated from spiked, treated foods and analyzed with respect to linear range and reaction efficiency. In most cases, the assay was linear over 6-8 orders of magnitude; lower limits of detection were 0.1-1 ppm and reaction efficiencies were within the preferred range of 100 +/- 10%. A notable exception occurred in the case of heat treatment at acidic pH, which resulted in severe delay or complete loss of amplification signals. Published by Elsevier Ltd.
C1 US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA.
RP Eischeid, AC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM Anne.Eischeid@fda.hhs.gov
FU U.S. Food and Drug Administration
FX This work was funded by the U.S. Food and Drug Administration. The
author would like to thank Sasha Kasko for help with autoclave
experiments.
NR 24
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U1 2
U2 21
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0956-7135
EI 1873-7129
J9 FOOD CONTROL
JI Food Control
PD JAN
PY 2016
VL 59
BP 393
EP 399
DI 10.1016/j.foodcont.2015.06.013
PG 7
WC Food Science & Technology
SC Food Science & Technology
GA CW3KA
UT WOS:000364890000052
ER
PT J
AU Jenkins, SV
Srivatsan, A
Reynolds, KY
Gao, F
Zhang, YB
Heyes, CD
Pandey, RK
Chen, JY
AF Jenkins, Samir V.
Srivatsan, Avinash
Reynolds, Kimberly Y.
Gao, Feng
Zhang, Yongbin
Heyes, Colin D.
Pandey, Ravindra K.
Chen, Jingyi
TI Understanding the interactions between porphyrin-containing
photosensitizers and polymer-coated nanoparticles in model biological
environments
SO JOURNAL OF COLLOID AND INTERFACE SCIENCE
LA English
DT Article
DE Gold nanostructure; Drug delivery; PEG coating; Controlled release
ID NON-SPECIFIC BINDING; NEAR-INFRARED LIGHT; GOLD NANOCAGES; PHOTODYNAMIC
THERAPY; DRUG-DELIVERY; THERANOSTIC APPLICATIONS; CONTROLLED-RELEASE;
RAMAN-SCATTERING; CANCER; ALBUMIN
AB Non-covalent incorporation of hydrophobic drugs into polymeric systems is a commonly-used strategy for drug delivery because non-covalent interactions minimize modification of the drug molecules whose efficacy is retained upon release. The behaviors of the drug-polymer delivery system in the biological environments it encounters will affect the efficacy of treatment. In this report, we have investigated the interaction between a hydrophobic drug and its encapsulating polymer in model biological environments using a photosensitizer encapsulated in a polymer-coated nanoparticle system. The photosensitizer, 3-(1'-hexyloxyethyl)-3-devinylpyropheophorbide-a (HPPH), was non-covalently incorporated to the poly(ethylene glycol) (PEG) layer coated on Au nanocages (AuNCs) to yield AuNC-HPPH complexes. The non-covalent binding was characterized by Scatchard analysis, fluorescence lifetime, and Raman experiments. The dissociation constant between PEG and HPPH was found to be similar to 35 mu M with a maximum loading of similar to 2.5 x 10(5) HPPHs/AuNC. The release was studied in serum-mimetic environment and in vesicles that model human cell membranes. The rate of protein-mediated drug release decreased when using a negatively-charged or cross-linked terminus of the surface-modified PEG. Furthermore, the photothermal effect of AuNCs can initiate burst release, and thus allow control of the release kinetics, demonstrating on-demand drug release. This study provides insights regarding the actions and release kinetics of non-covalent drug delivery systems in biological environments. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Jenkins, Samir V.; Reynolds, Kimberly Y.; Gao, Feng; Heyes, Colin D.; Chen, Jingyi] Univ Arkansas, Dept Chem & Biochem, Fayetteville, AR 72701 USA.
[Srivatsan, Avinash; Pandey, Ravindra K.] Roswell Pk Canc Inst, Photodynam Therapy Ctr, Buffalo, NY 14263 USA.
[Zhang, Yongbin] US FDA, NCTR ORA Nanotechnol Core Facil, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Chen, JY (reprint author), Univ Arkansas, Dept Chem & Biochem, Fayetteville, AR 72701 USA.
EM chenj@uark.edu
RI Chen, Jingyi/E-7168-2010
OI Chen, Jingyi/0000-0003-0012-9640
FU Arkansas Biosciences Institute; National Institutes of Health [NIH P30
GM103450]; Ralph E. Powe Jr. Faculty Enhancement Award; University of
Arkansas; Roswell Park Alliance; National Science Foundation
[CHE-1255440]; Student Undergraduate Research Fellowship (SURF)
FX This work was supported in part by the pilot project funds from the
Arkansas Biosciences Institute, the National Institutes of Health (NIH
P30 GM103450), the Ralph E. Powe Jr. Faculty Enhancement Award, and
startup funds from the University of Arkansas, to J.C.; the financial
support from Roswell Park Alliance to R.K.P.; and an appointment to
S.V.J. to the Summer Student Research Program at the National Center for
Toxicological Research administered by the Oak Ridge Institute for
Science and Education through an interagency agreement between the U.S.
Department of Energy and the U.S. Food and Drug Administration. C.D.H.
would like to thank the National Science Foundation (CHE-1255440) for
financial support. K.Y.R. thanks the support from Student Undergraduate
Research Fellowship (SURF). The views presented in this article do not
necessarily reflect those of the Food and Drug Administration.
NR 49
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U1 11
U2 106
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0021-9797
EI 1095-7103
J9 J COLLOID INTERF SCI
JI J. Colloid Interface Sci.
PD JAN 1
PY 2016
VL 461
BP 225
EP 231
DI 10.1016/j.jcis.2015.09.037
PG 7
WC Chemistry, Physical
SC Chemistry
GA CU3PN
UT WOS:000363437400032
PM 26402781
ER
PT J
AU Do, AB
Williams, K
Toomer, OT
AF Do, Andrew B.
Williams, Kristina
Toomer, Ondulla T.
TI In vitro digestibility and immunoreactivity of bovine milk proteins
SO FOOD CHEMISTRY
LA English
DT Article
DE Food allergens; Bovine whole milk; Digestibility models; Allergenicity
ID BETA-LACTOGLOBULIN; GASTRIC DIGESTION; VIVO DIGESTION; FOOD ALLERGENS;
FORMULAS; STABILITY; CASEIN; MODELS; HEALTH
AB Current models of digestibility solely utilize pepsin stability to assess the safety of allergenic food proteins. However, in vivo complete protein digestion requires acid denaturation and pepsin, trypsin, and/or chymotrypsin cleavage. This study aimed to identify the immunoreactivity and allergenicity of stable bovine milk proteins, using an improved digestibility model to simulate physiological gastric and intestinal conditions in vitro. Gel electrophoresis and immunoblot analysis were used to determine protein stability and immunoreactivity, respectively. Immunoreactivity of bovine milk proteins, beta-lactoglobulin (beta-LG) and casein (CN) was greatly diminished with gastric simulation (0-60 min), but some proteins were stable and immunoreactive with simulated intestinal digestive conditions (0-60 min). This study demonstrates the need for improved digestibility models for more accurate assessment of the behavior of food allergens in vivo. Published by Elsevier Ltd.
C1 [Do, Andrew B.; Williams, Kristina; Toomer, Ondulla T.] US FDA, Laurel, MD 20708 USA.
RP Toomer, OT (reprint author), US Dept Food & Drug Adm, Immunobiol Branch, Div Virulence Assessment, Off Appl Res & Safety Assessment,Ctr Food Safety, 8301 Muirkirk Rd,MOD 1,Room 2007, Laurel, MD 20708 USA.
EM Ondulla.Toomer@fda.hhs.gov
NR 22
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U1 9
U2 69
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0308-8146
EI 1873-7072
J9 FOOD CHEM
JI Food Chem.
PD JAN 1
PY 2016
VL 190
BP 581
EP 587
DI 10.1016/j.foodchem.2015.05.113
PG 7
WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics
SC Chemistry; Food Science & Technology; Nutrition & Dietetics
GA CS2SU
UT WOS:000361922800081
PM 26213013
ER
PT J
AU Tong, T
Ondov, JM
Buchholz, BA
VanDerveer, MC
AF Tong, T.
Ondov, J. M.
Buchholz, B. A.
VanDerveer, M. C.
TI Contemporary carbon content of bis (2-ethylhexyl) phthalate in butter
SO FOOD CHEMISTRY
LA English
DT Article
DE DEHP; AMS; Monte Carlo simulation; Fraction modern; Phthalate
ID DI-(2-ETHYLHEXYL) PHTHALATE; BIS(2-ETHYLHEXYL) PHTHALATE; DEHP;
DI(2-ETHYLHEXYL)PHTHALATE; EXPOSURE; RADIOCARBON; METABOLITES; CHEESE;
ESTERS; RISK
AB The fraction of naturally produced bis (2-ethylhexyl) phthalate (DEHP), a ubiquitous plasticizer known to contaminate packaged foods, was determined for each of five 1.10 kg samples of unsalted market butter by accelerator mass spectrometry (AMS). After extraction and concentration enrichment with liquid-liquid extraction, flash column chromatography, and preparative-scale high performance liquid chromatography, each sample provided approximate to 1250 mu g extracts of DEHP with carbon purity ranging from 92.5 +/- 1.2% (n = 3, 1 sigma) to 97.1 +/- 0.8% (n = 3, 1 sigma) as measured with gas chromatography mass spectrometry (GC-MS). After corrections for method blank DEHP, co-eluting compounds, and unidentified carbon, the mean fraction of naturally produced DEHP in butter was deterinined to be 0.16 +/- 0.12 (n = 5, 1 sigma). To our knowledge, this is the first report of the contemporary fraction of DEHP isolated from market butter in the U.S. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Tong, T.; Ondov, J. M.] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA.
[Buchholz, B. A.] Lawrence Livermore Natl Lab, Ctr Accelerator Mass Spectrometry, Livermore, CA 94551 USA.
[VanDerveer, M. C.] US FDA, Univ Stn, College Pk, MD 20740 USA.
RP Tong, T (reprint author), Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA.
EM ting@umd.edu
FU Joint Institute for Food Safety and Applied Nutrition (JIFSAN)
[U01FD001418]; U.S. Department of Energy by Lawrence Livermore National
Laboratory [DE-AC52-07NA27344]; NIGMS [8P41GM103483]
FX This work was funded by the Joint Institute for Food Safety and Applied
Nutrition (JIFSAN), grant # U01FD001418. This work performed in part
under the auspices of the U.S. Department of Energy by Lawrence
Livermore National Laboratory under Contract DE-AC52-07NA27344. Support
was provided by NIGMS 8P41GM103483. We sincerely thank all the above
institutes for their support.
NR 28
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U1 1
U2 37
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0308-8146
EI 1873-7072
J9 FOOD CHEM
JI Food Chem.
PD JAN 1
PY 2016
VL 190
BP 1064
EP 1068
DI 10.1016/j.foodchem.2015.06.053
PG 5
WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics
SC Chemistry; Food Science & Technology; Nutrition & Dietetics
GA CS2SU
UT WOS:000361922800145
PM 26213077
ER
PT J
AU Fauzi, MFA
Pennell, M
Sahiner, B
Chen, WJ
Shana'ah, A
Hemminger, J
Gru, A
Kurt, H
Losos, M
Joehlin-Price, A
Kavran, C
Smith, SM
Nowacki, N
Mansor, S
Lozanski, G
Gurcan, MN
AF Fauzi, Mohammad Faizal Ahmad
Pennell, Michael
Sahiner, Berkman
Chen, Weijie
Shana'ah, Arwa
Hemminger, Jessica
Gru, Alejandro
Kurt, Habibe
Losos, Michael
Joehlin-Price, Amy
Kavran, Christina
Smith, Stephen M.
Nowacki, Nicholas
Mansor, Sharmeen
Lozanski, Gerard
Gurcan, Metin N.
TI Classification of follicular lymphoma: the effect of computer aid on
pathologists grading
SO BMC MEDICAL INFORMATICS AND DECISION MAKING
LA English
DT Article
DE Follicular lymphoma grading; HPF detection; HPF classification; Digital
pathology
ID NON-HODGKINS-LYMPHOMA; WHOLE SLIDE IMAGES; SEGMENTATION; DIAGNOSES;
FRAMEWORK; PANEL
AB Background: Follicular lymphoma (FL) is one of the most common lymphoid malignancies in the western world. FL cases are stratified into three histological grades based on the average centroblast count per high power field (HPF). The centroblast count is performed manually by the pathologist using an optical microscope and hematoxylin and eosin (H&E) stained tissue section. Although this is the current clinical practice, it suffers from high inter-and intra-observer variability and is vulnerable to sampling bias.
Methods: In this paper, we present a system, called Follicular Lymphoma Grading System (FLAGS), to assist the pathologist in grading FL cases. We also assess the effect of FLAGS on accuracy of expert and inexperienced readers. FLAGS automatically identifies possible HPFs for examination by analyzing H&E and CD20 stains, before classifying them into low or high risk categories. The pathologist is first asked to review the slides according to the current routine clinical practice, before being presented with FLAGS classification via color-coded map. The accuracy of the readers with and without FLAGS assistance is measured.
Results: FLAGS was used by four experts (board-certified hematopathologists) and seven pathology residents on 20 FL slides. Access to FLAGS improved overall reader accuracy with the biggest improvement seen among residents. An average AUC value of 0.75 was observed which generally indicates "acceptable" diagnostic performance.
Conclusions: The results of this study show that FLAGS can be useful in increasing the pathologists' accuracy in grading the tissue. To the best of our knowledge, this study measure, for the first time, the effect of computerized image analysis on pathologists' grading of follicular lymphoma. When fully developed, such systems have the potential to reduce sampling bias by examining an increased proportion of HPFs within follicle regions, as well as to reduce inter- and intra-reader variability.
C1 [Fauzi, Mohammad Faizal Ahmad] Multimedia Univ, Fac Engn, Cyberjaya 63100, Selangor, Malaysia.
[Pennell, Michael] Ohio State Univ, Coll Publ Hlth, Div Biostat, Columbus, OH 43210 USA.
[Sahiner, Berkman; Chen, Weijie] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Shana'ah, Arwa; Hemminger, Jessica; Gru, Alejandro; Kurt, Habibe; Losos, Michael; Joehlin-Price, Amy; Kavran, Christina; Smith, Stephen M.; Nowacki, Nicholas; Mansor, Sharmeen; Lozanski, Gerard] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA.
[Gurcan, Metin N.] Ohio State Univ, Dept Biomed Informat, Columbus, OH 43210 USA.
RP Gurcan, MN (reprint author), Ohio State Univ, Dept Biomed Informat, 250 Lincoln Tower,1800 Cannon Dr, Columbus, OH 43210 USA.
EM metin.gurcan@osumc.edu
FU National Cancer Institute [R01CA134451, U24CA199374, U01 CA198945]
FX The project described was supported in part by Awards Number R01CA134451
(PIs: Gurcan, Lozanski), U24CA199374 (PIs: Gurcan, Madabushi, Martel),
and U01 CA198945 (PI: Bilgin) from the National Cancer Institute. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Cancer
Institute, or the National Institutes of Health. Certain commercial
materials and equipment are identified to specify experimental
procedures adequately. In no case does such identification imply
recommendation or endorsement by the Food and Drug Administration, nor
does it imply that the items identified are necessarily the best
available for the purpose.
NR 29
TC 2
Z9 2
U1 1
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6947
J9 BMC MED INFORM DECIS
JI BMC Med. Inform. Decis. Mak.
PD DEC 30
PY 2015
VL 15
AR 115
DI 10.1186/s12911-015-0235-6
PG 10
WC Medical Informatics
SC Medical Informatics
GA CZ9WC
UT WOS:000367446800002
PM 26715518
ER
PT J
AU Liang, X
Bittinger, K
Li, XW
Abernethy, DR
Bushman, FD
FitzGerald, GA
AF Liang, Xue
Bittinger, Kyle
Li, Xuanwen
Abernethy, Darrell R.
Bushman, Frederic D.
FitzGerald, Garret A.
TI Bidirectional interactions between indomethacin and the murine
intestinal microbiota
SO ELIFE
LA English
DT Article
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; HUMAN GUT MICROBIOTA;
BETA-GLUCURONIDASE INHIBITION; GASTROINTESTINAL MICROBIOTA; OBESITY;
MICE; COMMUNITIES; DIET; CHILDREN; BACTERIA
AB The vertebrate gut microbiota have been implicated in the metabolism of xenobiotic compounds, motivating studies of microbe-driven metabolism of clinically important drugs. Here, we studied interactions between the microbiota and indomethacin, a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenases (COX) -1 and -2. Indomethacin was tested in both acute and chronic exposure models in mice at clinically relevant doses, which suppressed production of COX-1- and COX-2-derived prostaglandins and caused small intestinal (SI) damage. Deep sequencing analysis showed that indomethacin exposure was associated with alterations in the structure of the intestinal microbiota in both dosing models. Perturbation of the intestinal microbiome by antibiotic treatment altered indomethacin pharmacokinetics and pharmacodynamics, which is probably the result of reduced bacterial mu-glucuronidase activity. Humans show considerable inter-individual differences in their microbiota and their responses to indomethacin thus, the drug-microbe interactions described here provide candidate mediators of individualized drug responses.
C1 [Liang, Xue; Li, Xuanwen; FitzGerald, Garret A.] Univ Penn, Perelman Sch Med, Dept Syst Pharmacol & Translat Therapeut, Philadelphia, PA 19104 USA.
[Bittinger, Kyle; Bushman, Frederic D.] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA.
[Abernethy, Darrell R.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA.
RP FitzGerald, GA (reprint author), Univ Penn, Perelman Sch Med, Dept Syst Pharmacol & Translat Therapeut, Philadelphia, PA 19104 USA.
EM garret@upenn.edu
FU National Heart, Lung, and Blood Institute [1U54HL117798]
FX National Heart, Lung, and Blood Institute 1U54HL117798 Xue Liang Xuanwen
Li Garret A Fitz Gerald; The funders had no role in study design, data
collection and interpretation, or the decision to submit the work for
publication.
NR 95
TC 4
Z9 4
U1 2
U2 2
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD DEC 23
PY 2015
VL 4
AR e08973
DI 10.7554/eLife.08973
PG 22
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DI9GG
UT WOS:000373809600001
PM 26701907
ER
PT J
AU Williams, AJ
Cooper, WM
Summage-West, CV
Sims, LM
Woodruff, R
Christman, J
Moskal, TJ
Ramsaroop, S
Sutherland, JB
Alusta, P
Wilkes, JG
Buzatu, DA
AF Williams, Anna J.
Cooper, Willie M.
Summage-West, Christine V.
Sims, Lillie M.
Woodruff, Robert
Christman, Jessica
Moskal, Ted J.
Ramsaroop, Shawn
Sutherland, John B.
Alusta, Pierre
Wilkes, Jon G.
Buzatu, Dan A.
TI Level 2 validation of a flow cytometric method for detection of
Escherichia coli O157:H7 in raw spinach
SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY
LA English
DT Article
DE Flow cytometry; Microorganisms; Food pathogens; Public health;
Escherichia coli O157
ID FOOD MATRIX INTERFERENCE; INFECTIONS; SEPARATION
AB The Bacteriological Analytical Manual (BAM) method currently used by the United States Food and Drug Administration (FDA) to detect Escherichia coli O157:H7 in spinach was systematically compared to a new flow cytometry based method. This Food and Drug Administration (FDA) level 2 external laboratory validation study was designed to determine the latter method's sensitivity and speed for analysis of this pathogen in raw spinach. Detection of target cell inoculations with a low cell count is critical, since enterohemorrhagic strains of E. coli require an infective dose of as few as 10 cells (Schmid-Hempel and Frank, 2007). Although, according to the FDA, the infectious dose is unknown (Food and Drug Administration, 1993). Therefore, the inoculation level into the spinach, a total of 2.0 +/- 2.6 viable E. coli O157 cells, was specified to yield between 25% and 75% detection by the new method, out of 20 samples (10 positives and 10 negatives). This criterion was met in that the new method detected 60% of the nominally positive samples; the corresponding sensitivity of the reference method was 50%. For both methods the most likely explanation for false negatives was that no viable cells were actually introduced into the sample. In this validation study, the flow cytometry method was equal to the BAM in sensitivity and far superior in speed. Published by Elsevier B.V.
C1 [Williams, Anna J.; Cooper, Willie M.; Alusta, Pierre; Wilkes, Jon G.; Buzatu, Dan A.] US FDA, Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA.
[Summage-West, Christine V.; Sims, Lillie M.] US FDA, Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA.
[Woodruff, Robert; Christman, Jessica] US FDA, Arkansas Reg Lab, Div Microbiol, Jefferson, AR 72079 USA.
[Ramsaroop, Shawn] Vivione Biosci LLC, Pine Bluff, AR 71602 USA.
[Sutherland, John B.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA.
RP Williams, AJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA.
EM anna.williams@fda.hhs.gov; willie.cooper@fda.hhs.gov;
christine.summage-west@fda.hhs.gov; lillie.sims@fda.hhs.gov;
robert.woodruff@fda.hhs.gov; jessica.christman@fda.hhs.gov;
tmoskal62@gmail.com; sramsaroop@vivionebiosciences.com;
john.sutherland@fda.hhs.gov; pierre.alusta@fda.hhs.gov;
jon.wilkes@fda.hhs.gov; dan.buzatu@fda.hhs.gov
OI Sutherland, John/0000-0003-4823-9822
NR 24
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Z9 0
U1 4
U2 27
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1605
EI 1879-3460
J9 INT J FOOD MICROBIOL
JI Int. J. Food Microbiol.
PD DEC 23
PY 2015
VL 215
BP 1
EP 6
DI 10.1016/j.ijfoodmicro.2015.08.011
PG 6
WC Food Science & Technology; Microbiology
SC Food Science & Technology; Microbiology
GA CV4NV
UT WOS:000364244700001
PM 26318407
ER
PT J
AU Behrens, AM
Lee, NG
Casey, BJ
Srinivasan, P
Sikorski, MJ
Daristotle, JL
Sandler, AD
Kofinas, P
AF Behrens, Adam M.
Lee, Nora G.
Casey, Brendan J.
Srinivasan, Priya
Sikorski, Michael J.
Daristotle, John L.
Sandler, Anthony D.
Kofinas, Peter
TI Biodegradable-Polymer-Blend-Based Surgical Sealant with
Body-Temperature-Mediated Adhesion
SO ADVANCED MATERIALS
LA English
DT Article
ID TISSUE ADHESIVES; POLYETHYLENE-GLYCOL; NANOFIBERS; ANASTOMOSIS;
COMPONENTS; SCAFFOLDS; HEMOSTATS; NANOSHEET; SURFACES; HYDROGEL
AB The development of practical and efficient surgical sealants has the propensity to improve operational outcomes. A biodegradable polymer blend is fabricated as a nonwoven fiber mat in situ. After direct deposition onto the tissue of interest, the material transitions from a fiber mat to a film. This transition promotes polymer-substrate interfacial interactions leading to improved adhesion and surgical sealant performance.
C1 [Behrens, Adam M.; Sikorski, Michael J.; Daristotle, John L.; Kofinas, Peter] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA.
[Lee, Nora G.; Srinivasan, Priya; Sandler, Anthony D.] Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA.
[Casey, Brendan J.] US FDA, Div Biol Chem & Mat Sci, Off Sci & Engn Labs, Off Med Prod & Tobacco,Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
RP Sandler, AD (reprint author), Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM ASandler@childrensnational.org; kofinas@umd.edu
OI Kofinas, Peter/0000-0001-6657-3037
FU National Institute of Biomedical Imaging and Bioengineering of the
National Institutes of Health [R01EB019963, F31EB019289]; Warren Citrin
Graduate Fellowship; Sheikh Zayed Institute for Pediatric Surgical
Innovation
FX Research reported in this publication was supported by the National
Institute of Biomedical Imaging and Bioengineering of the National
Institutes of Health under Award No. R01EB019963. A.M.B. was supported
by the National Institute of Biomedical Imaging and Bioengineering of
the National Institutes of Health under Award No, F31EB019289. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health. The authors would also like to acknowledge the Warren Citrin
Graduate Fellowship and the Sheikh Zayed Institute for Pediatric
Surgical Innovation for supporting this work, The mention of commercial
products, their sources, or their use in connection with material
reported herein is not to be construed as either an actual or implied
endorsement of such products by the Department of Health and Human
Services, The statements in this report should not be construed as
representing official agency policies.
NR 47
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U1 13
U2 57
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 0935-9648
EI 1521-4095
J9 ADV MATER
JI Adv. Mater.
PD DEC 22
PY 2015
VL 27
IS 48
BP 8056
EP 8061
DI 10.1002/adma.201503691
PG 6
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied;
Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA DA5JR
UT WOS:000367839900020
PM 26554545
ER
PT J
AU Duke, JC
Alexander, TN
Zhao, XQ
Delahanty, JC
Allen, JA
MacMonegle, AJ
Farrelly, MC
AF Duke, Jennifer C.
Alexander, Tesfa N.
Zhao, Xiaoquan
Delahanty, Janine C.
Allen, Jane A.
MacMonegle, Anna J.
Farrelly, Matthew C.
TI Youth's Awareness of and Reactions to The Real Cost National Tobacco
Public Education Campaign
SO PLOS ONE
LA English
DT Article
ID CESSATION MEDIA MESSAGES; ESTABLISHED SMOKING; SMOKERS; PROGRESSION;
VALIDATION; INTENTIONS; IMPACT; TRUTH
AB In 2014, the Food and Drug Administration (FDA) launched its first tobacco-focused public education campaign, The Real Cost, aimed at reducing tobacco use among 12- to 17-year-olds in the United States. This study describes The Real Cost message strategy, implementation, and initial evaluation findings. The campaign was designed to encourage youth who had never smoked but are susceptible to trying cigarettes (susceptible nonsmokers) and youth who have previously experimented with smoking (experimenters) to reassess what they know about the "costs" of tobacco use to their body and mind. The Real Cost aired on national television, online, radio, and other media channels, resulting in high awareness levels. Overall, 89.0% of U.S. youth were aware of at least one advertisement 6 to 8 months after campaign launch, and high levels of awareness were attained within the campaign's two targeted audiences: susceptible nonsmokers (90.5%) and experimenters (94.6%). Most youth consider The Real Cost advertising to be effective, based on assessments of ad perceived effectiveness (mean = 4.0 on a scale from 1.0 to 5.0). High levels of awareness and positive ad reactions are requisite proximal indicators of health behavioral change. Additional research is being conducted to assess whether potential shifts in population-level cognitions and/or behaviors are attributable to this campaign. Current findings demonstrate that The Real Cost has attained high levels of ad awareness which is a critical first step in achieving positive changes in tobacco-related attitudes and behaviors. These data can also be used to inform ongoing message and media strategies for The Real Cost and other U.S. youth tobacco prevention campaigns.
C1 [Duke, Jennifer C.; Allen, Jane A.; MacMonegle, Anna J.; Farrelly, Matthew C.] RTI Int, Res Triangle Pk, NC 27709 USA.
[Alexander, Tesfa N.; Zhao, Xiaoquan; Delahanty, Janine C.] US FDA, Ctr Tobacco Prod, Silver Spring, MD USA.
[Zhao, Xiaoquan] George Mason Univ, Dept Commun, Fairfax, VA 22030 USA.
RP Duke, JC (reprint author), RTI Int, Res Triangle Pk, NC 27709 USA.
EM jduke@rti.org
FU US Food and Drug Administration (FDA) [HHSF223201310001B]
FX The study was funded by the US Food and Drug Administration (FDA)
contract HHSF223201310001B. JCD, JAA, AJM, and MCF are all employees of
the company receiving the funding (RTI International)., Co-authors TNA
and JCD (2) are FDA employees and contributed to the writing and
preparation of the manuscript.
NR 29
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Z9 6
U1 10
U2 18
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 17
PY 2015
VL 10
IS 12
AR e0144827
DI 10.1371/journal.pone.0144827
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY9JO
UT WOS:000366723400028
PM 26679504
ER
PT J
AU Kontson, KL
AF Kontson, Kimberly L.
TI Your Brain on Art: Emergent Cortical Dynamics During Aesthetic
Experiences (vol 9, 626, 2015)
SO FRONTIERS IN HUMAN NEUROSCIENCE
LA English
DT Correction
DE EEG; machine learning; functional connectivity (FC); aesthetics; freely
moving
C1 [Kontson, Kimberly L.] US FDA, Off Sci & Engn Labs, Div Biomed Phys, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
RP Kontson, KL (reprint author), US FDA, Off Sci & Engn Labs, Div Biomed Phys, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
EM kimberly.kontson@fda.hhs.gov
NR 1
TC 0
Z9 0
U1 5
U2 7
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-5161
J9 FRONT HUM NEUROSCI
JI Front. Hum. Neurosci.
PD DEC 16
PY 2015
VL 9
AR 684
DI 10.3389/fnhum.2015.00684
PG 1
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA CZ4CA
UT WOS:000367049400001
PM 26733853
ER
PT J
AU Wang, X
Peden, K
Murata, H
AF Wang, Xiao
Peden, Keith
Murata, Haruhiko
TI RT-qPCR-based microneutralization assay for human cytomegalovirus using
fibroblasts and epithelial cells
SO VACCINE
LA English
DT Article
DE Reverse transcription quantitative PCR; Virus-neutralization assay; Cell
lysate; Human cytomegalovirus; Epithelial cell; Fibroblast
ID NEUTRALIZING ANTIBODY-RESPONSE; CONGENITAL CYTOMEGALOVIRUS; QUANTITATIVE
PCR; HYPERIMMUNE GLOBULIN; NATURAL INFECTION; ENDOTHELIAL-CELLS;
GENE-EXPRESSION; COMPLEX; TROPISM; VIRUS
AB Human cytomegalovirus (HCMV) is a leading cause of congenital infection that can result in serious disabilities in affected children. To facilitate HCMV vaccine development, a microscale neutralization assay based on reverse transcription quantitative PCR (RT-qPCR) was developed to quantify HCMV-neutralizing antibodies. Our approach relies on the generation of crude lysates from virus-infected cells that are amenable to direct analysis by RT-qPCR, thereby circumventing rate-limiting procedures associated with sample RNA extraction and purification. By serial passaging of the laboratory HCMV strain AD169 in epithelial cells (ARPE-19), a revertant virus with restored epithelial cell tropism, designated AD169(wt131), was obtained. AD169 and AD169wt131 were evaluated in both epithelial cells (ARPE-19) and fibroblasts (MRC-5) by one-step RT-qPCR targeting the immediate-early gene IE1 transcript of HCMV. Expression kinetics indicated that RT-qPCR assessment could be conducted as early as 6 h post-infection. Human serum samples (n =30) from healthy donors were tested for HCMV-specific IgG using a commercially available ELISA and for HCMV-neutralizing activity using our RT-qPCR-based neutralization assay. In agreement with the ELISA results, higher neutralizing activity was observed in the HCMV IgG seropositive group when compared with the HCMV IgG seronegative group. In addition, HCMV IgG seropositive human sera exhibited higher neutralizing titers using epithelial cells compared with using fibroblasts (geometric mean titers of 344 and 8 in ARPE-19 cells and MRC-5 cells, respectively). Our assay was robust to variation in input virus dose. In addition, a simple lysis buffer containing a non-ionic detergent was successfully demonstrated to be a less costly alternative to commercial reagents for cell-lysate preparation. Thus, our rapid HCMV neutralization assay may be a straightforward and flexible high-throughput tool for measuring antibody responses induced by vaccination and natural infection. Published by Elsevier Ltd.
C1 [Wang, Xiao; Peden, Keith; Murata, Haruhiko] US FDA, Lab DNA Viruses, Div Viral Prod, Off Vaccines Res & Review,Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
RP Murata, H (reprint author), US FDA, 10903 New Hampshire Ave,Bldg 52-72,Room 1312, Silver Spring, MD 20993 USA.
EM haruhiko.murata@fda.hhs.gov
FU FDA intramural research fund (CBER Targeted Funding for Modernizing
Science); Oak Ridge Institute for Science and Education Fellowship; FDA
intramural research fund (FDA Office of Minority Health Challenge Grant)
FX This work was supported by FDA intramural research funds (CBER Targeted
Funding for Modernizing Science and FDA Office of Minority Health
Challenge Grant). X.W. was supported by an Oak Ridge Institute for
Science and Education Fellowship. We are grateful to Evi Struble and
Andrew M. Lewis Jr. for comments on the manuscript.
NR 43
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U1 1
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD DEC 16
PY 2015
VL 33
IS 51
BP 7254
EP 7261
DI 10.1016/j.vaccine.2015.10.110
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA CZ0FD
UT WOS:000366779600019
PM 26552003
ER
PT J
AU Parker, CH
Khuda, SE
Pereira, M
Ross, MM
Fu, TJ
Fan, XB
Wu, Y
Williams, KM
DeVries, J
Pulvermacher, B
Bedford, B
Zhang, X
Jackson, LS
AF Parker, Christine H.
Khuda, Sefat E.
Pereira, Marion
Ross, Mark M.
Fu, Tong-Jen
Fan, Xuebin
Wu, Yan
Williams, Kristina M.
DeVries, Jonathan
Pulvermacher, Brian
Bedford, Binaifer
Zhang, Xi
Jackson, Lauren S.
TI Multi-allergen Quantitation and the Impact of Thermal Treatment in
Industry-Processed Baked Goods by ELISA and Liquid Chromatography-Tandem
Mass Spectrometry
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE food allergens; baked goods; thermal processing; ELISA; mass
spectrometry
ID IMMUNOCHEMICAL ANALYTICAL METHODS; MAJOR PEANUT ALLERGENS; EGG-WHITE
PROTEINS; ARA H 2; DARK CHOCOLATE; FOOD ALLERGENS; MULTIPLE ALLERGENS;
ARACHIS-HYPOGAEA; TEST KITS; MATRIX
AB Undeclared food allergens account for 30-40% of food recalls in the United States. Compliance with ingredient labeling regulations and the implementation of effective manufacturing allergen control plans require the use of reliable methods for allergen detection and quantitation in complex food products. The objectives of this work were to (1) produce industry-processed model foods incurred with egg, milk, and peanut allergens, (2) compare analytical method performance for allergen quantitation in thermally processed bakery products, and (3) determine the effects of thermal treatment on allergen detection. Control and allergen-incurred cereal bars and muffins were formulated in a pilot-scale industry processing facility. Quantitation of egg, milk, and peanut in incurred baked goods was compared at various processing stages using commercial enzyme-linked immunosorbent assay (ELISA) kits and a novel multi-allergen liquid chromatography (LC)-tandem mass spectrometry (MS/MS) multiple-reaction monitoring (MRM) method. Thermal processing was determined to negatively affect the recovery and quantitation of egg, milk, and peanut to different extents depending on the allergen, matrix, and analytical test method. The Morinaga ELISA and LC-MS/MS quantitative methods reported the highest recovery across all monitored allergens, whereas the ELISA Systems, Neogen BioKits, Neogen Veratox, and R-Biopharm ELISA Kits underperformed in the determination of allergen content of industry-processed bakery products.
C1 [Parker, Christine H.; Ross, Mark M.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Khuda, Sefat E.; Pereira, Marion; Williams, Kristina M.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA.
[Fu, Tong-Jen; Bedford, Binaifer; Jackson, Lauren S.] US FDA, Ctr Food Safety & Appl Nutr, Bedford Pk, IL 60501 USA.
[DeVries, Jonathan; Pulvermacher, Brian] James Ford Bell Tech Ctr, Golden Valley, MN 55427 USA.
[Fan, Xuebin; Wu, Yan; Zhang, Xi] IIT, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA.
RP Jackson, LS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 6502 South Archer Rd, Bedford Pk, IL 60501 USA.
EM Lauren.Jackson@fda.hhs.gov
FU U.S. Food and Drug Administration (FDA), Center for Food Safety and
Applied Nutrition (CFSAN); FDA Office of the Chief Scientist; FDA
[5U01FD003801]
FX This research was funded by the U.S. Food and Drug Administration (FDA),
Center for Food Safety and Applied Nutrition (CFSAN), and by the FDA
Office of the Chief Scientist. In addition, this project was supported
in part by Grant 5U01FD003801 from the FDA to the Illinois Institute of
Technology Institute for Food Safety and Health and by appointments to
the Research Participation Program administered by the Oak Ridge
Institute for Science and Education (ORISE) through an interagency
agreement between the U.S. Department of Energy and the FDA.
NR 62
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U1 7
U2 27
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0021-8561
EI 1520-5118
J9 J AGR FOOD CHEM
JI J. Agric. Food Chem.
PD DEC 16
PY 2015
VL 63
IS 49
BP 10669
EP 10680
DI 10.1021/acs.jafc.5b04287
PG 12
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA CZ1OC
UT WOS:000366874200010
PM 26595064
ER
PT J
AU Loftfield, E
Freedman, ND
Graubard, BI
Guertin, KA
Black, A
Huang, WY
Shebl, FM
Mayne, ST
Sinha, R
AF Loftfield, Erikka
Freedman, Neal D.
Graubard, Barry I.
Guertin, Kristin A.
Black, Amanda
Huang, Wen-Yi
Shebl, Fatma M.
Mayne, Susan T.
Sinha, Rashmi
TI Association of Coffee Consumption With Overall and Cause-Specific
Mortality in a Large US Prospective Cohort Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE additives; caffeine; cause-specific mortality; coffee; mortality
ID DOSE-RESPONSE METAANALYSIS; CARDIOVASCULAR-DISEASE;
MYOCARDIAL-INFARCTION; DECAFFEINATED COFFEE; CANCER INCIDENCE; CAFFEINE
INTAKE; LIVER-CANCER; RISK; QUESTIONNAIRE; DRINKING
AB Concerns about high caffeine intake and coffee as a vehicle for added fat and sugar have raised questions about the net impact of coffee on health. Although inverse associations have been observed for overall mortality, data for cause-specific mortality are sparse. Additionally, few studies have considered exclusively decaffeinated coffee intake or use of coffee additives. Coffee intake was assessed at baseline by self-report in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Hazard ratios were estimated using Cox proportional hazards models. Among 90,317 US adults without cancer at study baseline (1998-2001) or history of cardiovascular disease at study enrollment (1993-2001), 8,718 deaths occurred during 805,644 person-years of follow-up from 1998 through 2009. Following adjustment for smoking and other potential confounders, coffee drinkers, as compared with nondrinkers, had lower hazard ratios for overall mortality (< 1 cup/day: hazard ratio (HR) = 0.99 (95% confidence interval (CI): 0.92, 1.07); 1 cup/day: HR = 0.94 (95% CI: 0.87, 1.02); 2-3 cups/day: HR = 0.82 (95% CI: 0.77, 0.88); 4-5 cups/day: HR = 0.79 (95% CI: 0.72, 0.86); >= 6 cups/day: HR = 0.84 (95% CI: 0.75, 0.95)). Similar findings were observed for decaffeinated coffee and coffee additives. Inverse associations were observed for deaths from heart disease, chronic respiratory diseases, diabetes, pneumonia and influenza, and intentional self-harm, but not cancer. Coffee may reduce mortality risk by favorably affecting inflammation, lung function, insulin sensitivity, and depression.
C1 [Loftfield, Erikka; Freedman, Neal D.; Graubard, Barry I.; Guertin, Kristin A.; Black, Amanda; Huang, Wen-Yi; Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Loftfield, Erikka; Shebl, Fatma M.; Mayne, Susan T.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA.
[Shebl, Fatma M.; Mayne, Susan T.] Yale Univ, Ctr Canc, New Haven, CT USA.
[Mayne, Susan T.] US Dept HHS, Ctr Food Safety & Appl Nutr, Food & Drug Adm, College Pk, MD USA.
RP Loftfield, E (reprint author), NCI, NCI Shady Grove, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, 9609 Med Ctr Dr 6E332, Rockville, MD 20850 USA.
EM erikka.loftfield@nih.gov
FU Yale-National Cancer Institute predoctoral training grant [T32
CA105666]; Intramural Research Program of National Institutes of Health,
National Cancer Institute
FX This study was supported in part by a Yale-National Cancer Institute
predoctoral training grant (grant T32 CA105666) to S.T.M. and by the
Intramural Research Program of the National Institutes of Health,
National Cancer Institute.
NR 42
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U1 11
U2 35
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD DEC 15
PY 2015
VL 182
IS 12
BP 1010
EP 1022
DI 10.1093/aje/kwv146
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CY8AD
UT WOS:000366629900005
PM 26614599
ER
PT J
AU Bachmann, LH
Manhart, LE
Martin, DH
Sena, AC
Dimitrakoff, J
Jensen, JS
Gaydos, CA
AF Bachmann, Laura H.
Manhart, Lisa E.
Martin, David H.
Sena, Arlene C.
Dimitrakoff, Jordan
Jensen, Jorgen Skov
Gaydos, Charlotte A.
TI Advances in the Understanding and Treatment of Male Urethritis
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE urethritis; men; Chlamydia trachomatis; Mycoplasma genitalium; Neisseria
gonorrhoeae
ID MYCOPLASMA-GENITALIUM; NONGONOCOCCAL URETHRITIS; UREAPLASMA-UREALYTICUM;
CHLAMYDIA-TRACHOMATIS; GONOCOCCAL URETHRITIS; BACTERIAL VAGINOSIS; GRAM
STAIN; MEN; AZITHROMYCIN; ASSOCIATION
AB Neisseria gonorrhoeae and Chlamydia trachomatis are well-documented urethral pathogens, and the literature supporting Mycoplasma genitalium as an etiology of urethritis is growing. Trichomonas vaginalis and viral pathogens (herpes simplex virus types 1 and 2 and adenovirus) can cause urethritis, particularly in specific sub-populations. New data are emerging regarding the potential role of bacterial vaginosis-associated bacteria in urethritis, although results are inconsistent regarding the pathogenic role of Ureaplasma urealyticum in men. Mycoplasma hominis and Ureaplasma parvum do not appear to be pathogens. Men with suspected urethritis should undergo evaluation to confirm urethral inflammation and etiologic cause. Although nucleic acid amplification testing would detect N. gonorrhoeae and C. trachomatis (or T. vaginalis if utilized), there is no US Food and Drug Administration-approved clinical test for M. genitalium available in the United States at this time. The varied etiologies of urethritis and lack of diagnostic options for some organisms present treatment challenges in the clinical setting.
C1 [Bachmann, Laura H.] Wake Forest Univ Hlth Sci, Dept Med, Div Infect Dis, Winston Salem, NC 27157 USA.
[Manhart, Lisa E.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Manhart, Lisa E.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Martin, David H.] Louisiana State Univ, Dept Med, Div Infect Dis, New Orleans, LA USA.
[Sena, Arlene C.] Univ N Carolina, Sch Med, Div Infect Dis, Chapel Hill, NC USA.
[Dimitrakoff, Jordan] Beth Israel Deaconess Med Ctr, Div Obstet Gynecol & Reprod Biol, Boston, MA USA.
[Dimitrakoff, Jordan] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Dimitrakoff, Jordan] US FDA, Div Bone Reprod & Urol Prod, Silver Spring, MD USA.
[Jensen, Jorgen Skov] Statens Serum Inst, Microbiol & Infect Control, DK-2300 Copenhagen, Denmark.
[Gaydos, Charlotte A.] Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA.
RP Bachmann, LH (reprint author), Wake Forest Univ Hlth Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM lbachman@wakehealth.edu
FU Centers for Disease Control and Prevention
FX This article appears as part of the supplement "Evidence Papers for the
CDC Sexually Transmitted Diseases Treatment Guidelines," sponsored by
the Centers for Disease Control and Prevention.
NR 44
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U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD DEC 15
PY 2015
VL 61
SU 8
BP S763
EP S769
DI 10.1093/cid/civ755
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CY5RX
UT WOS:000366466200002
PM 26602615
ER
PT J
AU Yu, DAK
Tolleson, WH
Knox, B
Jin, YQ
Guo, L
Guo, YL
Kadlubar, SA
Ning, BT
AF Yu, Dianke
Tolleson, William H.
Knox, Bridgett
Jin, Yaqiong
Guo, Lei
Guo, Yongli
Kadlubar, Susan A.
Ning, Baitang
TI Modulation of ALDH5A1 and SLC22A7 by microRNA hsa-miR-29a-3p in human
liver cells
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE microRNA; hsa-miR-29a-3p; ALDH5A1; SLC22A7; Drug metabolizing enzymes
and transporters; Pharmacogenomics
ID DRUG-METABOLIZING-ENZYMES; THERAPEUTIC TARGET; GASTRIC-CANCER;
TRANSPORTERS; FIBROSIS; MIR-29; POLYMORPHISMS; EXPRESSION; FAMILY;
PHARMACOGENETICS
AB Observed variations in drug responses among patients may result from differences in heritable genetic traits or from alterations in the epigenetic regulation of drug metabolizing enzymes and transporters (DMETs). MicroRNAs (miRNAs), a group of small non-coding RNAs, provide an epigenetic mechanism for fine-tuning the expression of targeted DMET genes by regulating the efficiency of protein translation and by decreasing mRNA stability via enhanced degradation. In the current study we systematically screened 374 important genes encoding DMETs for potential response elements to hsa-miR-29a-3p, a highly abundant miRNA in human liver. RNA electrophoresis mobility shift assays displayed direct interactions between hsa-miR-29a-3p and its cognate targets within the mRNA transcripts for the ABCC6, SLC22A7 and ALDH5A1 genes. The expression of luciferase reporter genes containing the 3'-UTRs of SLC22A7 or ALDH5A1 and the expression of endogenous SLC22A7 and ALDH5A1 were each suppressed by transfection with hsa-miR-29a-3p mimics. Importantly, chemically-induced up-regulation of hsa-miR-29a-3p correlated inversely with the expression of SLC22A7 and ALDH5A1. However, our studies failed to detect suppressive effects of hsa-miR-29a-3p on ABCC6 expression, which might be explained by the notion that the interaction of hsa-miR-29a-3p and ABCC6 mRNA was unable to recruit ribonucleoproteins to form a RNA-induced silencing complex. Published by Elsevier Inc.
C1 [Yu, Dianke; Tolleson, William H.; Knox, Bridgett; Guo, Lei; Ning, Baitang] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Jin, Yaqiong; Guo, Yongli] Capital Med Univ, Beijing Childrens Hosp, Beijing 100045, Peoples R China.
[Kadlubar, Susan A.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
RP Ning, BT (reprint author), Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT100, Jefferson, AR 72079 USA.
EM baitang.ning@fda.hhs.gov
OI Jin, Ya-Qiong/0000-0002-9318-6531
FU National Center for Toxicological Research [E0752601]; U.S. Food and
Drug Administration
FX This study was supported and funded by the National Center for
Toxicological Research (Project E0752601), U.S. Food and Drug
Administration.
NR 52
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U1 1
U2 11
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
EI 1873-2968
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD DEC 15
PY 2015
VL 98
IS 4
BP 671
EP 680
DI 10.1016/j.bcp.2015.09.020
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CY1EU
UT WOS:000366150300012
PM 26428001
ER
PT J
AU Hunter, NL
O'Callaghan, KM
Califf, RM
AF Hunter, Nina L.
O'Callaghan, Kathryn M.
Califf, Robert M.
TI Engaging Patients Across the Spectrum of Medical Product Development
View From the US Food and Drug Administration
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Hunter, Nina L.; O'Callaghan, Kathryn M.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Califf, Robert M.] US FDA, Off Med Prod & Tobacco, Silver Spring, MD 20993 USA.
RP Califf, RM (reprint author), US FDA, 10903 New Hampshire Ave,Bldg 1,Room 2314, Silver Spring, MD 20993 USA.
EM robert.califf@fda.hhs.gov
NR 6
TC 12
Z9 13
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD DEC 15
PY 2015
VL 314
IS 23
BP 2499
EP 2500
DI 10.1001/jama.2015.15818
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CY4PV
UT WOS:000366391500011
PM 26584067
ER
PT J
AU Worley, RR
Fisher, J
AF Worley, Rachel Rogers
Fisher, Jeffrey
TI Application of physiologically-based pharmacokinetic modeling to explore
the role of kidney transporters in renal reabsorption of
perfluorooctanoic acid in the rat
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE PFOA; PBPK; Oatp1a1; Oat1; Oat3; IVIVE
ID ORGANIC ANION TRANSPORTERS; AMMONIUM PERFLUOROOCTANOATE;
SEX-DIFFERENCES; TISSUE DISTRIBUTION; PRODUCTION WORKERS; LIVER-ENZYMES;
FEMALE RATS; IN-VITRO; ELIMINATION; EXCRETION
AB Renal elimination and the resulting clearance of perfluorooctanoic acid (PFOA) from the serum exhibit pronounced sex differences in the adult rat. The literature suggests that this is largely due to hormonally regulated expression of organic anion transporters (OATS) on the apical and basolateral membranes of the proximal tubule cells that facilitate excretion and reabsorption of PFOA from the filtrate into the blood. Previously developed PBPK models of PFOA exposure in the rat have not been parameterized to specifically account for transporter-mediated renal elimination. We developed a PBPK model for PFOA in male and female rats to explore the role of Oat1, Oat3, and Oatp1a1 in sex-specific renal reabsorption and excretion of PFOA. Descriptions of the kinetic behavior of these transporters were extrapolated from in vitro studies and the model was used to simulate time-course serum, liver, and urine data for intravenous (IV) and oral exposures in both sexes. Model predicted concentrations of PFOA in the liver, serum, and urine showed good agreement with experimental data for both male and female rats indicating that in vitro derived physiological descriptions of transporter-mediated renal reabsorption can successfully predict sex-dependent excretion of PFOA in the rat. This study supports the hypothesis that sex-specific serum half-lives for PFOA are largely driven by expression of transporters in the kidney and contribute to the development of PBPK modeling as a tool for evaluating the role of transporters in renal clearance. Published by Elsevier Inc.
C1 [Worley, Rachel Rogers] Agcy Tox Subst & Dis Registry, Div Community Hlth Invest, Atlanta, GA 30341 USA.
[Worley, Rachel Rogers; Fisher, Jeffrey] Univ Georgia, Interdisciplinary Toxicol Program, Athens, GA 30602 USA.
[Fisher, Jeffrey] Natl Ctr Toxicol Res, Food & Drug Adm, Jefferson, AR 72079 USA.
RP Worley, RR (reprint author), Agcy Tox Subst & Dis Registry, 4770 Buford Highway, Atlanta, GA 30341 USA.
EM idz7@cdc.gov
FU University of Georgia's Graduate School and Interdisciplinary Toxicology
Program
FX We would like to thank Dr. Eva McLanahan and Dr. Clement Welsh at the
Agency for Toxic Substances and Disease Registry and Dr. Xiaoxia Yang,
Dr. Luisa Camacho, and Dr. Fred Beland at the National Center for
Toxicological Research for their helpful discussion and comments.
Partial financial support was from the University of Georgia's Graduate
School and Interdisciplinary Toxicology Program.
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U1 8
U2 15
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
EI 1096-0333
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD DEC 15
PY 2015
VL 289
IS 3
BP 428
EP 441
DI 10.1016/j.taap.2015.10.017
PG 14
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA CY1EF
UT WOS:000366148800008
PM 26522833
ER
PT J
AU Yang, XX
Doerge, DR
Teeguarden, JG
Fisher, JW
AF Yang, Xiaoxia
Doerge, Daniel R.
Teeguarden, Justin G.
Fisher, Jeffrey W.
TI Development of a physiologically based pharmacokinetic model for
assessment of human exposure to bisphenol A
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Bisphenol A; BPA; Physiologically based pharmacokinetic model; PBPK;
Human
ID SPRAGUE-DAWLEY RATS; ROUTE DEPENDENT DOSIMETRY; TANDEM
MASS-SPECTROMETRY; IN-VITRO; METABOLIC-CLEARANCE; ENTEROHEPATIC
CIRCULATION; LIQUID-CHROMATOGRAPHY; DRUG CLEARANCE; SERUM PROFILES;
HUMAN URINE
AB A previously developed physiologically based pharmacokinetic (PBPK) model for bisphenol A (BPA) in adult rhesus monkeys was modified to characterize the pharmacokinetics of BPA and its phase II conjugates in adult humans following oral ingestion. Coupled with in vitro studies on BPA metabolism in the liver and the small intestine, the PBPK model was parameterized using oral pharmacokinetic data with deuterated-BPA (d(6)-BPA) delivered in cookies to adult humans after overnight fasting. The availability of the serum concentration time course of unconjugated d(6)-BPA offered direct empirical evidence for the calibration of BPA model parameters. The recalibrated PBPK adult human model for BPA was then evaluated against published human pharmacokinetic studies with BPA. A hypothesis of decreased oral uptake was needed to account for the reduced peak levels observed in adult humans, where d(6)-BPA was delivered in soup and food was provided prior to BPA ingestion, suggesting the potential impact of dosing vehicles and/or fasting on BPA disposition. With the incorporation of Monte Carlo analysis, the recalibrated adult human model was used to address the inter-individual variability in the internal dose metrics of BPA for the U.S. general population. Model-predicted peak BPA serum levels were in the range of pM, with 95% of human variability falling within an order of magnitude. This recalibrated PBPK model for BPA in adult humans provides a scientific basis for assessing human exposure to BPA that can serve to minimize uncertainties incurred during extrapolations across doses and species. Published by Elsevier Inc.
C1 [Yang, Xiaoxia; Doerge, Daniel R.; Fisher, Jeffrey W.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
[Teeguarden, Justin G.] Pacific NW Natl Lab, Hlth Effects & Exposure Sci, Richland, WA 99352 USA.
[Teeguarden, Justin G.] Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA.
RP Yang, XX (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM xiaoxia.yang@fda.hhs.gov
FU U.S. Food and Drug Administration/National Center for the Toxicological
Research
FX This work was supported by the U.S. Food and Drug
Administration/National Center for the Toxicological Research. The
authors gratefully acknowledge the help with statistics from Dr. Nysia
George, and the critical review of this manuscript by Drs. Barry
Delclos, Jia-Long Fang, Jason Aungst, and Frederick A. Beland. The
manuscript does not necessarily reflect the views of the U.S. Food and
Drug Administration. The authors have no conflict of interest.
NR 73
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U2 40
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
EI 1096-0333
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD DEC 15
PY 2015
VL 289
IS 3
BP 442
EP 456
DI 10.1016/j.taap.2015.10.016
PG 15
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA CY1EF
UT WOS:000366148800009
PM 26522835
ER
PT J
AU Agnihothram, SS
Basco, MDS
Mullis, L
Foley, SL
Hart, ME
Sung, K
Azevedo, MP
AF Agnihothram, Sudhakar S.
Basco, Maria D. S.
Mullis, Lisa
Foley, Steven L.
Hart, Mark E.
Sung, Kidon
Azevedo, Marli P.
TI Infection of Murine Macrophages by Salmonella enterica Serovar
Heidelberg Blocks Murine Norovirus Infectivity and Virus-induced
Apoptosis
SO PLOS ONE
LA English
DT Article
ID MITOCHONDRIAL PERMEABILITY TRANSITION; PROGRAMMED CELL-DEATH;
EPITHELIAL-CELLS; UNITED-STATES; ACTIVATION; LIPOPOLYSACCHARIDE;
GASTROENTERITIS; PATHOGENESIS; AUTOPHAGY; BACTERIA
AB Gastroenteritis caused by bacterial and viral pathogens constitutes a major public health threat in the United States accounting for 35% of hospitalizations. In particular, Salmonella enterica and noroviruses cause the majority of gastroenteritis infections, with emergence of sporadic outbreaks and incidence of increased infections. Although mechanisms underlying infections by these pathogens have been individually studied, little is known about the mechanisms regulating co-infection by these pathogens. In this study, we utilized RAW 264.7 murine macrophage cells to investigate the mechanisms governing co-infection with S. enterica serovar Heidelberg and murine norovirus (MNV). We demonstrate that infection of RAW 264.7 cells with S. enterica reduces the replication of MNV, in part by blocking virus entry early in the virus life cycle, and inducing antiviral cytokines later in the infection cycle. In particular, bacterial infection prior to, or during MNV infection affected virus entry, whereas MNV entry remained unaltered when the virus infection preceded bacterial invasion. This block in virus entry resulted in reduced virus replication, with the highest impact on replication observed during conditions of co-infection. In contrast, bacterial replication showed a threefold increase in MNV-infected cells, despite the presence of antibiotic in the medium. Most importantly, we present evidence that the infection of MNV-infected macrophages by S. enterica blocked MNV-induced apoptosis, despite allowing efficient virus replication. This apoptosis blockade was evidenced by reduction in DNA fragmentation and absence of poly-ADP ribose polymerase (PARP), caspase 3 and caspase 9 cleavage events. Our study suggests a novel mechanism of pathogenesis whereby initial co-infection with these pathogens could result in prolonged infection by either of these pathogens or both together.
C1 [Agnihothram, Sudhakar S.; Basco, Maria D. S.; Mullis, Lisa; Foley, Steven L.; Hart, Mark E.; Sung, Kidon; Azevedo, Marli P.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Azevedo, MP (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
EM Marli.Azevedo@fda.hhs.gov
FU Food and Drug Administration
FX The Study was supported by Intramural Funding From the Food and Drug
Administration.
NR 56
TC 3
Z9 3
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 14
PY 2015
VL 10
IS 12
AR e0144911
DI 10.1371/journal.pone.0144911
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY9GR
UT WOS:000366715900146
PM 26658916
ER
PT J
AU Racoosin, JA
Seymour, SM
Cascio, L
Gill, R
AF Racoosin, Judith A.
Seymour, Sally M.
Cascio, Laurelle
Gill, Rajdeep
TI Serious Neurologic Events after Epidural Glucocorticoid Injection - The
FDA's Risk Assessment
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Racoosin, Judith A.] US FDA, Ctr Drug Evaluat & Res, Div Anesthesia Analgesia & Addict Prod, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA.
[Seymour, Sally M.] US FDA, Ctr Drug Evaluat & Res, Div Pulm Allergy & Rheumatol Prod, Off Surveillance & Epidemiol, Silver Spring, MD USA.
[Cascio, Laurelle] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Off Surveillance & Epidemiol, Silver Spring, MD USA.
[Cascio, Laurelle] US FDA, Ctr Drug Evaluat & Res, Div Pharmacovigilance, Off Surveillance & Epidemiol, Silver Spring, MD USA.
[Gill, Rajdeep] US FDA, Ctr Drug Evaluat & Res, Div Epidemiol, Off Surveillance & Epidemiol, Silver Spring, MD USA.
RP Racoosin, JA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Anesthesia Analgesia & Addict Prod, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA.
NR 5
TC 9
Z9 10
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD DEC 10
PY 2015
VL 373
IS 24
BP 2299
EP 2301
DI 10.1056/NEJMp1511754
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA CY0QW
UT WOS:000366111600003
PM 26444582
ER
PT J
AU Lu, TP
Chen, JJ
AF Lu, Tzu-Pin
Chen, James J.
TI Subgroup identification for treatment selection in biomarker adaptive
design
SO BMC MEDICAL RESEARCH METHODOLOGY
LA English
DT Article
DE Adaptive signature design; Classification; Personalized medicine;
Predictive classifier; Subgroup analysis; Subgroup selection
ID EARLY PREDICTIVE BIOMARKER; HIGH-DIMENSIONAL DATA; CELL LUNG-CANCER;
CLINICAL-TRIALS; SURVIVAL PREDICTION; SIGNATURE DESIGN; GENE SIGNATURE;
RANDOM FORESTS; DRUG; CLASSIFICATION
AB Background: Advances in molecular technology have shifted new drug development toward targeted therapy for treatments expected to benefit subpopulations of patients. Adaptive signature design (ASD) has been proposed to identify the most suitable target patient subgroup to enhance efficacy of treatment effect. There are two essential aspects in the development of biomarker adaptive designs: 1) an accurate classifier to identify the most appropriate treatment for patients, and 2) statistical tests to detect treatment effect in the relevant population and subpopulations. We propose utilization of classification methods to identity patient subgroups and present a statistical testing strategy to detect treatment effects.
Methods: The diagonal linear discriminant analysis (DLDA) is used to identify targeted and non-targeted subgroups. For binary endpoints, DLDA is directly applied to classify patient into two subgroups; for continuous endpoints, a two-step procedure involving model fitting and determination of a cutoff-point is used for subgroup classification. The proposed strategy includes tests for treatment effect in all patients and in a marker-positive subgroup, with a possible follow-up estimation of treatment effect in the marker-negative subgroup. The proposed method is compared to the ASD classification method using simulated datasets and two publically available cancer datasets.
Results: The DLDA-based classifier performs well in terms of sensitivity, specificity, positive and negative predictive values, and accuracy in the simulation data and the two cancer datasets, with superior accuracy compared to the ASD method. The subgroup testing strategy is shown to be useful in detecting treatment effect in terms of power and control of study-wise error.
Conclusion: Accuracy of a classifier is essential for adaptive designs. A poor classifier not only assigns patients to inappropriate treatments, but also reduces the power of the test, resulting in incorrect conclusions. The proposed procedure provides an effective approach for subgroup identification and subgroup analysis.
C1 [Lu, Tzu-Pin; Chen, James J.] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Lu, Tzu-Pin] Natl Taiwan Univ, Inst Epidemiol & Prevent Med, Dept Publ Hlth, Taipei 10764, Taiwan.
[Chen, James J.] China Med Univ, Grad Inst Biostat, Taichung, Taiwan.
RP Chen, JJ (reprint author), US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT 20, Jefferson, AR 72079 USA.
EM jamesj.chen@fda.hhs.gov
FU National Taiwan University, Taiwan
FX This work was supported in part by the National Taiwan University,
Taiwan. The funders had no roles in design, in the collection, the
analysis, the interpretation of data; in the writing the manuscript; and
in the decision to submit the manuscript for publication. The views
presented in this paper are those of the authors and do not necessarily
represent those of the U.S. Food and Drug Administration.
NR 44
TC 1
Z9 1
U1 4
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2288
J9 BMC MED RES METHODOL
JI BMC Med. Res. Methodol.
PD DEC 9
PY 2015
VL 15
AR 105
DI 10.1186/s12874-015-0098-7
PG 10
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA CY5SY
UT WOS:000366468900001
PM 26646831
ER
PT J
AU Panda, R
Fiedler, KL
Cho, CY
Cheng, R
Stutts, WL
Jackson, LS
Garber, EAE
AF Panda, Rakhi
Fiedler, Katherine L.
Cho, Chung Y.
Cheng, Raymond
Stutts, Whitney L.
Jackson, Lauren S.
Garber, Eric A. E.
TI Effects of a Pro line Endopeptidase on the Detection and Quantitation of
Gluten by Antibody-Based Methods during the Fermentation of a Model
Sorghum Beer
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE gluten; proline endopeptidase; beer; fermentation
ID CELIAC-DISEASE; ASPERGILLUS-NIGER; MASS-SPECTROMETRY;
MONOCLONAL-ANTIBODIES; HYDROLYZED GLUTEN; COMPETITIVE ELISA; DEGRADING
ENZYME; T-CELLS; GLIADIN; ENDOPROTEASE
AB The effectiveness of a proline endopeptidase (PEP) in hydrolyzing gluten and its putative immunopathogenic sequences was examined using antibody-based methods and mass spectrometry (MS). Based on the results of the antibody-based methods, fermentation of wheat gluten containing sorghum beer resulted in a reduction in the detectable gluten concentration. The addition of PEP further reduced the gluten concentration. Only one sandwich ELISA was able to detect the apparent low levels of gluten present in the beers. A competitive ELISA using a pepsin-trypsin hydrolysate calibrant was unreliable because the peptide profiles of the beers were inconsistent with that of the hydrolysate calibrant. Analysis by MS indicated that PEP enhanced the loss of a fragment of an immunopathogenic 33-mer peptide in the beer. However, Western blot results indicated partial resistance of the high molecular weight (HMW) glutenins to the action of PEP, questioning the ability of PEP in digesting all immunopathogenic sequences present in gluten.
C1 [Panda, Rakhi; Cho, Chung Y.; Garber, Eric A. E.] FDA, Div Bioanalyt Chem, Off Regulatory Sci, CFSAN, College Pk, MD 20740 USA.
[Fiedler, Katherine L.; Stutts, Whitney L.] FDA, Div Analyt Chem, Off Regulatory Sci, CFSAN, College Pk, MD 20740 USA.
[Cheng, Raymond] Univ Maryland, JIFSAN, College Pk, MD 20740 USA.
[Jackson, Lauren S.] FDA, Div Food Proc Sci & Technol, Off Food Safety, CFSAN, Bedford Pk, IL 60501 USA.
RP Panda, R (reprint author), FDA, Div Bioanalyt Chem, Off Regulatory Sci, CFSAN, College Pk, MD 20740 USA.
EM Rakhi.Panda@fda.hhs.gov
NR 50
TC 3
Z9 3
U1 4
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0021-8561
EI 1520-5118
J9 J AGR FOOD CHEM
JI J. Agric. Food Chem.
PD DEC 9
PY 2015
VL 63
IS 48
BP 10525
EP 10535
DI 10.1021/acs.jafc.5b04205
PG 11
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA CY3WN
UT WOS:000366340700020
PM 26548701
ER
PT J
AU Nichol, G
Brown, S
Becker, L
Merchant, R
Abella, B
Eloff, B
Youngquist, S
Salcido, D
Tisherman, S
Valenzuela, T
Daya, M
Elrod, J
Fly, D
May, S
Sayre, M
AF Nichol, Graham
Brown, Siobhan
Becker, Lance
Merchant, Raina
Abella, Ben
Eloff, Benjamin
Youngquist, Scott
Salcido, David
Tisherman, Sara
Valenzuela, Terry
Daya, Mohamud
Elrod, JoAnn
Fly, Deborah
May, Susanne
Sayre, Michael
TI Natural History of Automated External Defibrillators in Public Locations
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association / Resuscitation
Science Symposium
CY NOV 15-19, 2015
CL Chicago, IL
SP Amer Heart Assoc
DE Cardiac Arrest; AEDs; Public Health
C1 [Nichol, Graham] Univ Washington, Harborview Ctr Prehosp Emergency Care, Gen Internal Med, Seattle, WA 98195 USA.
[Brown, Siobhan; Elrod, JoAnn; Fly, Deborah; Sayre, Michael] Univ Washington, Harborview Ctr Prehosp Emergency Care, Seattle, WA 98195 USA.
[Becker, Lance; Merchant, Raina; Abella, Ben] Univ Penn, Philadelphia, PA 19104 USA.
[Eloff, Benjamin] US FDA, Silver Spring, MD USA.
[Youngquist, Scott] Univ Utah, Salt Lake City, UT USA.
[Salcido, David; Tisherman, Sara] Univ Pittsburgh, Pittsburgh, PA USA.
[Valenzuela, Terry] Univ Arizona, Tucson, AZ USA.
[Daya, Mohamud] Oregon Hlth & Sci Univ, Portland, OR USA.
[May, Susanne] Univ Washington, Seattle, WA 98195 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD DEC 8
PY 2015
VL 132
IS 23
MA 23288
BP 2284
EP 2284
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CX7DH
UT WOS:000365861100056
ER
PT J
AU Nyan, DC
Swinson, KL
AF Nyan, Dougbeh-Chris
Swinson, Kevin L.
TI A novel multiplex isothermal amplification method for rapid detection
and identification of viruses
SO SCIENTIFIC REPORTS
LA English
DT Article
ID UNITED-STATES; INFECTION; ASSAY; DNA
AB A rapid multiplex isothermal amplification assay has been developed for detection and identification of multiple blood-borne viruses that infect millions of people world-wide. These infections may lead to chronic diseases or death if not diagnosed and treated in a timely manner. Sets of virusspecific oligonucleotides and oligofluorophores were designed and used in a reverse-transcription loop-mediated multiplexed isothermal amplification reaction for detection and gel electrophoretic identification of human Immunodeficiency virus (HIV), hepatitis-B virus (HBV), hepatitis-C virus (HCV), hepatitis-E virus (HEV), dengue virus (DENV), and West Nile (WNV) virus infection in blood plasma. Amplification was catalyzed with two thermostable enzymes for 30-60 minutes under isothermal condition, utilizing a simple digital heat source. Electrophoretic analysis of amplified products demonstrated simultaneous detection of 6 viruses that were distinctly identified by unique ladder-like banding patterns. Naked-eye fluorescent visualization of amplicons revealed intensely fluorescing products that indicated positive detection. The test demonstrated a 97% sensitivity and a 100% specificity, with no cross-reaction with other viruses observed. This portable detection tool may have clinical and field utility in the developing and developed world settings. This may enable rapid diagnosis and identification of viruses for targeted therapeutic intervention and prevention of disease transmission.
C1 [Nyan, Dougbeh-Chris] US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
[Swinson, Kevin L.] Morgan State Univ, Dept Biol, Baltimore, MD 21239 USA.
RP Nyan, DC (reprint author), US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
EM dnyan@doctor.com; kevin.swinson@morgan.edu
FU Fellowship-Appointment of the Oak Ridge Institute for Science and
Education (ORISE)
FX This work was supported by a Fellowship-Appointment of the Oak Ridge
Institute for Science and Education (ORISE). The findings and
conclusions of this study are those of the authors and not
representative of ORISE, the US Food and Drug Administration (FDA), the
Department of Health and Human Services, or the Morgan State University.
The authors memorialize the late Dr. William G. Coleman Jr., Scientific
Director of the National Institute on Minority Health and Health
Disparities at the NIH and late Father, Charles S. J. Nyan, Jr. for
their outstanding mentoring. The authors also thank the following: Dr.
Richard Sacra, M. D. of Samaritan's Purse for reviewing this manuscript;
Valerie Winkelman, Dr. Phillip Williamson, and Dr. Maria Rios for
clinical donor samples; Elizabeth Martinez, Laura Ulitzky, Dr. Deborah
Taylor, and Livia Alves-Lima for technical and logistical assistance.
NR 23
TC 1
Z9 1
U1 4
U2 42
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD DEC 8
PY 2015
VL 5
AR 17925
DI 10.1038/srep17925
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CX8PB
UT WOS:000365964900001
PM 26643761
ER
PT J
AU Bakshi, N
Lukombo, I
Belfer, I
Krishnamurti, L
AF Bakshi, Nitya
Lukombo, Ines
Belfer, Inna
Krishnamurti, Lakshmanan
TI Impact of Psychological Covariates on Experimental Pain Sensitivity in
Children and Adolescents with SCD
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Bakshi, Nitya; Krishnamurti, Lakshmanan] Emory Univ, Aflac Canc & Blood Disorders Ctr, Childrens Healthcare Atlanta, Atlanta, GA 30322 USA.
[Lukombo, Ines] Univ Pittsburgh, Pittsburgh, PA USA.
[Belfer, Inna] US FDA, CDER, Silver Spring, MD USA.
[Belfer, Inna] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019003109
ER
PT J
AU Hakim, FT
Memon, S
Jin, P
Imanguli, MM
Rehman, N
Yan, XY
Rose, JJ
Mays, JW
Dhamala, S
Kapoor, V
Telford, W
Halverson, DC
Baird, K
Fowler, DH
Stroncek, D
Cowen, EW
Pavletic, SZ
Gress, RE
AF Hakim, Frances T.
Memon, Sarfraz
Jin, Ping
Imanguli, Matin M.
Rehman, Najibah
Yan, Xiao-Yi
Rose, Jeremy J.
Mays, Jacqueline W.
Dhamala, Susan
Kapoor, Veena
Telford, William
Halverson, David C.
Baird, Kristin
Fowler, Daniel H.
Stroncek, David
Cowen, Edward W.
Pavletic, Steven Z.
Gress, Ronald E.
TI Upregulation of Interferon-Inducible and Damage Response Receptors in
Chronic Graft-Versus-Host Disease
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Hakim, Frances T.; Memon, Sarfraz; Imanguli, Matin M.; Rehman, Najibah; Yan, Xiao-Yi; Rose, Jeremy J.; Dhamala, Susan; Kapoor, Veena; Telford, William; Halverson, David C.; Fowler, Daniel H.; Pavletic, Steven Z.; Gress, Ronald E.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Jin, Ping] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
[Mays, Jacqueline W.] Natl Inst Dent & Craniofacial Res, Clin Res Core, NIH, Bethesda, MD USA.
[Baird, Kristin] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Baird, Kristin] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
[Stroncek, David] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Cowen, Edward W.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019003046
ER
PT J
AU Goswami, M
Prince, GT
Biancotto, A
Moir, S
Cheung, F
Kutliarov, Y
Dunham, K
Chen, JG
Shi, RY
Zhou, HZ
Golding, H
Tang, JR
Tsang, JS
Dickler, HB
Noonan, K
Smith, BD
Burrello, IM
Hourigan, CS
AF Goswami, Meghali
Prince, Gabrielle T.
Biancotto, Angelique
Moir, Susan
Cheung, Foo
Kutliarov, Yuri
Dunham, Kimberly
Chen, Jinguo
Shi, Rongye
Zhou, Huizhi
Golding, Hana
Tang, Jingrong
Tsang, John S.
Dickler, Howard B.
Noonan, Kimberly
Smith, B. Douglas
Burrello, Ivan M.
Hourigan, Christopher S.
TI Impaired Response to Influenza Vaccination in AML Patients
Post-Chemotherapy Associated with a Highly Atypical B-Cell Profile
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Goswami, Meghali; Hourigan, Christopher S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Goswami, Meghali] George Washington Univ, Inst Biomed Sci, Washington, DC USA.
[Prince, Gabrielle T.; Noonan, Kimberly] Johns Hopkins Sch Med, Baltimore, MD USA.
[Biancotto, Angelique; Cheung, Foo; Kutliarov, Yuri; Chen, Jinguo; Shi, Rongye; Zhou, Huizhi; Tsang, John S.; Dickler, Howard B.; Hourigan, Christopher S.] NIH, Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 20892 USA.
[Moir, Susan] NIAID, Immunopathogenesis Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Dunham, Kimberly] NCI, Leidos Biomed Res Inc, Frederick, MD 21701 USA.
[Golding, Hana] US FDA, Silver Spring, MD USA.
[Tang, Jingrong] NHLBI, Myeloid Malignancies Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Tsang, John S.] NIAID, Syst Genom & Bioinformat Unit, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
[Smith, B. Douglas] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Burrello, Ivan M.] Johns Hopkins Sch Med, Sidney Kimmel Canc Ctr, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020104309
ER
PT J
AU Hunt, R
Yalamanoglu, A
Back, JH
Butler, S
Schiller, T
Wong, E
Buehler, PW
Kimchi-Sarfaty, C
AF Hunt, Ryan
Yalamanoglu, Ayla
Back, Jin Hyen
Butler, Stephen
Schiller, Tal
Wong, Edward
Buehler, Paul W.
Kimchi-Sarfaty, Chava
TI A Mechanistic Investigation of the TTP-like State Associated with
Intravenous Abuse of Opana (R) ER
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Hunt, Ryan; Yalamanoglu, Ayla; Back, Jin Hyen; Schiller, Tal; Buehler, Paul W.; Kimchi-Sarfaty, Chava] US FDA, Div Hematol Res & Review, OBRR, CBER, Silver Spring, MD USA.
[Butler, Stephen] Reg Kidney Care, Kingsport, TN USA.
[Wong, Edward] Childrens Natl Med Ctr, Div Lab Med, Washington, DC 20010 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020105087
ER
PT J
AU Parker, CH
Stutts, WL
DeGrasse, SL
AF Parker, Christine H.
Stutts, Whitney L.
DeGrasse, Stacey L.
TI Development and Validation of a Liquid Chromatography-Tandem Mass
Spectrometry Method for the Quantitation of Microcystins in Blue-Green
Algal Dietary Supplements
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE microcystin; cyanotoxin; blue-green algae; dietary supplements;
Aphanizomenon flos-aquae; tandem mass spectrometry
ID APHANIZOMENON-FLOS-AQUAE; CYANOBACTERIUM NODULARIA-SPUMIGENA;
SOLID-PHASE EXTRACTION; HUMAN HEALTH-RISK; FOOD SUPPLEMENTS; WATER;
TOXINS; CYANOTOXINS; BRAZIL; ASSAY
AB A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous detection and quantitation of seven microcystin congeners (1-7) and nodularin-R (8) in blue-green algal dietary supplements. Single-laboratory method validation data were collected in four supplement matrices (capsule, liquid, powder, and tablet) fortified at toxin concentrations from 0.25-2.00 mu g/g (ppm). Average recoveries and relative standard deviations (RSD) using matrix-corrected solvent calibration curves were 101% (6% RSD) for all congeners and supplements investigated. Limits of detection (0.006-0.028 mu g/g) and quantitation (0.018-0.084 mu g/g) were sufficient to confirm the presence of microcystin contamination at the Oregon-mandated guidance concentration of 1.0 mu g of microcystin-LReq/g. Quantitated concentrations of microcystin contamination in market-available Aphanizomenon flos-aquae blue-green algal supplements ranged from 0.18-1.87 mu g of microcystin-LReq/g for detected congeners microcystin-LR, microcystin-LA, and microcystin-LY (3-5). Microcystin-RR, -YR, -LW, and -LF and nodularin-R (1, 2, and 6-8) were not detected in the supplements examined.
C1 [Parker, Christine H.; Stutts, Whitney L.; DeGrasse, Stacey L.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
RP Parker, CH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM Christine.Parker@fda.hhs.gov
FU U.S. Food and Drug Administration, Center for Food Safety and Applied
Nutrition
FX This research is supported by the U.S. Food and Drug Administration,
Center for Food Safety and Applied Nutrition.
NR 47
TC 1
Z9 2
U1 11
U2 29
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0021-8561
EI 1520-5118
J9 J AGR FOOD CHEM
JI J. Agric. Food Chem.
PD DEC 2
PY 2015
VL 63
IS 47
BP 10303
EP 10312
DI 10.1021/acs.jafc.5b04292
PG 10
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA CX8CK
UT WOS:000365930000013
PM 26466789
ER
PT J
AU Sullivan, HW
Campbell, M
AF Sullivan, Helen W.
Campbell, Miriam
TI Do Prescription Drug Ads Tell Consumers Enough About Benefits and Side
Effects? Results From the Health Information National Trends Survey,
Fourth Administration
SO JOURNAL OF HEALTH COMMUNICATION
LA English
DT Article
ID FACTS BOX; TELEVISION; ADVERTISEMENTS; AMERICANS; HARMS
AB Direct-to-consumer prescription drug advertising (DTCA) is a major source of consumer information about prescription drugs. The present study updates 2002 U.S. Food and Drug Administration phone survey questions that found that 44% and 61% of consumers thought that DTCA did not include enough information about benefits and risks, respectively. The present study was administered by mail using a nationally representative sample, and provides a more in-depth understanding of how these beliefs relate to demographic and health characteristics. Data collected from 3,959 respondents to the National Cancer Institute's 2011 Health Information National Trends Survey find results similar to the 2002 survey: 46% and 52% of respondents thought that DCTA did not include enough information about benefits and risks, respectively. Respondents fell into four groups: 23% agreed that DTCA tells enough about drug benefits and risks, 41% disagreed, 18% expressed no opinion, and 18% had discordant beliefs. DTCA attitudes were negatively associated with education, income, and whether respondents purchase prescription drugs; attitudes were positively associated with whether respondents understand prescription drug information. This study confirms that a plurality of Americans believe that DTCA does not include enough information about benefits and risks, suggesting that the educational effect of DTCA could be improved.
C1 [Sullivan, Helen W.; Campbell, Miriam] US FDA, Silver Spring, MD 20993 USA.
RP Sullivan, HW (reprint author), US FDA, 10903 New Hampshire Ave,Bldg 51, Silver Spring, MD 20993 USA.
EM helen.sullivan@fda.hhs.gov
NR 36
TC 2
Z9 2
U1 0
U2 13
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1081-0730
EI 1087-0415
J9 J HEALTH COMMUN
JI J. Health Commun.
PD DEC 2
PY 2015
VL 20
IS 12
BP 1391
EP 1396
DI 10.1080/10810730.2015.1018635
PG 6
WC Communication; Information Science & Library Science
SC Communication; Information Science & Library Science
GA CW8XO
UT WOS:000365282900004
PM 26120940
ER
PT J
AU Kaverin, NV
Rudneva, IA
Timofeeva, TA
Ignatieva, AV
Shilov, AA
Bovin, NV
Ilyushina, NA
AF Kaverin, Nikolai V.
Rudneva, Irina A.
Timofeeva, Tatiana A.
Ignatieva, Anna V.
Shilov, Aleksandr A.
Bovin, Nicolai V.
Ilyushina, Natalia A.
TI Pleiotropic effects of amino acid substitutions in H5 hemagglutinin of
influenza A escape mutants
SO VIRUS RESEARCH
LA English
DT Article
DE Influenza escape mutants; H5 hemagglutinin; Pleiotropic
antibody-neutralizing; mutations
ID RECEPTOR-BINDING; ANTIGENIC SPECIFICITY; VIRUS; REPLICATION; ADAPTATION;
ANTIBODIES; MUTATIONS; VIRULENCE; MOLECULE; EPITOPES
AB We believe that the monitoring of pleiotropic effects of the hemagglutinin (HA) mutations found in H5 escape mutants is essential for accurate prediction of mutants with pandemic potential. In the present study, we assessed multiple characteristics of antibody-selected HA mutations. We examined the pH optimum of fusion, HA heat inactivation, affinity to sialyl receptors, and in vitro and in vivo replication kinetics of various influenza H5 escape mutants. Several amino acid substitutions, including T108I, K152E, R162G, and K218N, reduced the stability of HA as determined by heat inactivation, whereas S128L and T215A substitutions were associated with significant increases in HA thermostability compared to the respective wild-type viruses. HA mutations at positions 108, 113, 115, 121, 123, 128, 162, and 190 and substitutions at positions 123, 199, and 215 affected the replicative ability of H5 escape mutants in vitro and in vivo, respectively. The T108I substitution lowered the pH optimum of fusion and HA temperature stability while increasing viral replicative ability. Taken together, a co-variation between antigenic specificity and different HA phenotypic properties has been demonstrated. Published by Elsevier B.V.
C1 [Kaverin, Nikolai V.; Rudneva, Irina A.; Timofeeva, Tatiana A.; Ignatieva, Anna V.; Shilov, Aleksandr A.] DI Ivanovskii Inst Virol, Moscow 123098, Russia.
[Bovin, Nicolai V.] MM Shemyakin Inst Bioorgan Chem, Moscow 117997, Russia.
[Ilyushina, Natalia A.] FDA CDER, Silver Spring, MD 20993 USA.
RP Ilyushina, NA (reprint author), FDA CDER, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM Natalia.Ilyushina@fda.hhs.gov
FU Russian Foundation for Basic Research (RFBR) [13-04-00257]
FX We are especially grateful to Dr. Larisa V. Mochalova for helpful
discussions and help with the experiments on HA receptor specificity.
The work was supported by grant #13-04-00257 of Russian Foundation for
Basic Research (RFBR).
NR 34
TC 1
Z9 1
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
EI 1872-7492
J9 VIRUS RES
JI Virus Res.
PD DEC 2
PY 2015
VL 210
BP 81
EP 89
DI 10.1016/j.virusres.2015.07.016
PG 9
WC Virology
SC Virology
GA CX1KQ
UT WOS:000365455500013
PM 26220479
ER
PT J
AU Amen, O
Vemula, SV
Zhao, J
Ibrahim, R
Hussein, A
Hewlett, IK
Moussa, S
Mittal, SK
AF Amen, O.
Vemula, S. V.
Zhao, J.
Ibrahim, R.
Hussein, A.
Hewlett, I. K.
Moussa, S.
Mittal, S. K.
TI Identification and characterization of a highly pathogenic H5N1 avian
influenza A virus during an outbreak in vaccinated chickens in Egypt
SO VIRUS RESEARCH
LA English
DT Article
DE Highly pathogenic avian influenza; Influenza A; H5N1; Poultry; H5N1
vaccine
ID HEMAGGLUTININ; POULTRY; MICE; EPIDEMIOLOGY; PROTECTION; ANTIBODIES;
INFECTION; PEPTIDE; AFRICA; BIRDS
AB Highly pathogenic avian influenza A (HPAI) H5N1 viruses continue to be a major veterinary and public health problem in Egypt. Continued surveillance of these viruses is necessary to devise strategies to control the spread of the virus and to monitor its evolutionary patterns. This is a report of the identification of a variant strain of HPAI H5N1 virus during an outbreak in 2010 in vaccinated chicken flocks in a poultry farm in Assiut, Egypt. Vaccination of chickens with an oil-emulsified inactivated A/chicken/Mexico/232/94 (H5N2) vaccine induced high levels of hemagglutination inhibition (HI) antibody titers reaching up to 9 log2. However, all flocks irrespective of the number of vaccine doses and the resultant HI titer levels came down with severe influenza infections. The qRT-PCR and rapid antigen test confirmed the influenza virus to be from H5N1 subtype. Sequencing of the hemagglutinin (HA) gene fragment from ten independent samples demonstrated that a single H5N1 strain was involved. This strain belonged to clade 2.2.1 and had several mutations in the receptor-binding site of the HA protein, thereby producing a variant strain of HPAI H5N1 virus which was antigenically different from the parent clade 2.2.1 virus circulating in Egypt at that time. In order to define the variability in HPAI H5N1 viruses over time in Egypt, we sequenced another H5N1 virus that was causing infections in chickens in 2014. Phylogenetic analysis revealed that both viruses had further distanced from the parent virus circulating during 2010. This study highlights that the antigenic mutations in HPAI H5N1 viruses represent a definitive challenge for the development of an effective vaccine for poultry. Overall, the results emphasize the need for continued surveillance of H5N1 outbreaks and extensive characterization of virus isolates from vaccinated and non-vaccinated poultry populations to better understand genetic changes and their implications. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Amen, O.; Mittal, S. K.] Purdue Univ, Coll Vet Med, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA.
[Amen, O.; Ibrahim, R.; Moussa, S.] Assiut Univ, Poultry Dis Dept, Fac Vet Med, Assiut 71526, Egypt.
[Vemula, S. V.; Zhao, J.; Hewlett, I. K.] US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Silver Spring, MD 20993 USA.
[Hussein, A.] Assiut Univ, Dept Anim Hyg, Fac Vet Med, Assiut 71526, Egypt.
RP Mittal, SK (reprint author), Purdue Univ, Coll Vet Med, Dept Comparat Pathobiol, 725 Harrison St, W Lafayette, IN 47907 USA.
EM mittal@purdue.ed
OI Zhao, Jiangqin/0000-0003-4672-0735
FU Ministry of Higher Education, Egyptian Government; PVM Hatch Fund
FX This work was partially supported by the fellowship from the Ministry of
Higher Education, Egyptian Government and the PVM Hatch Fund. We thank
Jane Kovach for her secretarial assistance. The findings and conclusions
in this article have not been formally disseminated by the Food and Drug
Administration and should not be construed to represent any Agency
determination or policy.
NR 34
TC 2
Z9 2
U1 2
U2 15
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
EI 1872-7492
J9 VIRUS RES
JI Virus Res.
PD DEC 2
PY 2015
VL 210
BP 337
EP 343
DI 10.1016/j.virusres.2015.09.004
PG 7
WC Virology
SC Virology
GA CX1KQ
UT WOS:000365455500046
PM 26363196
ER
PT J
AU Sae, D
Cheng, CM
Khan, AA
AF Bae, Dongryeoul
Cheng, Chorng-Ming
Khan, Ashraf A.
TI Characterization of extended-spectrum beta-lactamase (ESBL) producing
non-typhoidal Salmonella (NTS) from imported food products
SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY
LA English
DT Article
DE Salmonella enterica; Food; ESBL; Antimicrobial resistance; Conjugation
ID ACTIVE SURVEILLANCE NETWORK; 10 US SITES; ANTIMICROBIAL RESISTANCE;
UNITED-STATES; MOLECULAR CHARACTERIZATION; RETAIL MEATS;
ESCHERICHIA-COLI; CLINICAL-SAMPLES; ENTERICA; PREVALENCE
AB Food contaminated with extended-spectrum beta-lactamase (ESBL)-producing Salmonella enterica has emerged as an important global issue due to the international food-product trade. Therefore, the purpose of this study was to investigate whether imported food products can serve as a reservoir for non-typhoidal Salmonella (NTS) that can transmit beta-lactam-resistance to humans through ingestion of the contaminated food. NTS isolates (n = 110) were collected from various imported food products (n = 3480) from 2011 to 2013. The NTS isolates were analyzed by serotyping, antimicrobial susceptibility tests, and plasmid profiling. Salmonella ser. Weltevreden, Salmonella ser. Newport, Salmonella ser. Senftenberg, Salmonella ser. Virchow, Salmonella ser. Enteritidis, Salmonella ser. Typhimurium, and salmonella ser. Bareilly were the most prevalent serovars. Nine NTS strains were resistant to ampicillin and/or one or more cephalosporins (MIC > 32 mu g/mL). Polymerase chain reaction (PCR) detection revealed that all nine isolates carried the bla(TEM-1) beta-lactamase gene, with or without the bla(CTX-M-9) or bla(OXA-1) genes. Two isolates, PSS_913 and PSS_988, exhibited decreased susceptibility to extended-spectrum cephalosporins and ampicillin. Plasmids ranging in size from less than 8 to over 165 kbp, from all of the 9 resistant isolates, belonged to the IncHI1, Incl1, IncN, or IncX groups. Conjugation experiments and Southern hybridization, using bla(TEM-1), confirmed the plasmid-mediated transfer of ESBL genes, which resulted in increased MICs of beta-lactams for Escherichia coli transconjugants. The contamination of imported food products by NTS with conjugative plasmid-borne ESBL genes may contribute to the spread of ESBL-producing NTS and compromise the therapeutic activity of extended-spectrum beta-lactam antibiotics. Published by Elsevier B.V.
C1 [Bae, Dongryeoul; Khan, Ashraf A.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA.
[Cheng, Chorng-Ming] US FDA, Pacific Reg Lab Southwest, Irvine, CA 92612 USA.
RP Khan, AA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA.
EM Ashraf.khan@fda.hhs.gov
NR 55
TC 0
Z9 0
U1 7
U2 36
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1605
EI 1879-3460
J9 INT J FOOD MICROBIOL
JI Int. J. Food Microbiol.
PD DEC 2
PY 2015
VL 214
BP 12
EP 17
DI 10.1016/j.ijfoodmicro.2015.07.017
PG 6
WC Food Science & Technology; Microbiology
SC Food Science & Technology; Microbiology
GA CV4RF
UT WOS:000364253500003
ER
PT J
AU Mossoba, ME
Flynn, TJ
Vohra, S
Wiesenfeld, PL
Sprando, RL
AF Mossoba, Miriam E.
Flynn, Thomas J.
Vohra, Sanah
Wiesenfeld, Paddy L.
Sprando, Robert L.
TI Human kidney proximal tubule cells are vulnerable to the effects of
Rauwolfia serpentina
SO CELL BIOLOGY AND TOXICOLOGY
LA English
DT Article
DE Kidney proximal tubule; Rauwolfia serpentina; Nephrotoxicity; HK-2
ID INDOLE ALKALOIDS; HYPERTENSION; INJURY; HK-2; CYTOTOXICITY; EXTRACT;
ASSAY; ROOT
AB Rauwolfia serpentina (or Snake root plant) is a botanical dietary supplement marketed in the USA for maintaining blood pressure. Very few studies have addressed the safety of this herb, despite its wide availability to consumers. Its reported pleiotropic effects underscore the necessity for evaluating its safety. We used a human kidney cell line to investigate the possible negative effects of R. serpentina on the renal system in vitro, with a specific focus on the renal proximal tubules. We evaluated cellular and mitochondrial toxicity, along with a variety of other kidney-specific toxicology biomarkers. We found that R. serpentina was capable of producing highly detrimental effects in our in vitro renal cell system. These results suggest more studies are needed to investigate the safety of this dietary supplement in both kidney and other target organ systems.
C1 [Mossoba, Miriam E.; Flynn, Thomas J.; Vohra, Sanah; Wiesenfeld, Paddy L.; Sprando, Robert L.] US FDA, CFSAN, OARSA, DOT,NIVTB, Laurel, MD 20708 USA.
[Mossoba, Miriam E.] US FDA, MOD Labs 1, 8301 Muirkirk Rd,HFS-025,Lab 1406, Laurel, MD 20708 USA.
RP Mossoba, ME (reprint author), US FDA, MOD Labs 1, 8301 Muirkirk Rd,HFS-025,Lab 1406, Laurel, MD 20708 USA.
EM miriam.mossoba@fda.hhs.gov
NR 41
TC 1
Z9 1
U1 1
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0742-2091
EI 1573-6822
J9 CELL BIOL TOXICOL
JI Cell Biol. Toxicol.
PD DEC
PY 2015
VL 31
IS 6
BP 285
EP 293
DI 10.1007/s10565-016-9311-7
PG 9
WC Cell Biology; Toxicology
SC Cell Biology; Toxicology
GA DG5JH
UT WOS:000372113500003
PM 26838987
ER
PT J
AU Cope, JU
Rosenthal, GL
Weinel, P
Odegaard, A
Murphy, DM
AF Cope, Judith U.
Rosenthal, Geoffrey L.
Weinel, Pamela
Odegaard, Amy
Murphy, Dianne M.
TI FDA Safety Reviews on Drugs, Biologics, and Vaccines: 2007-2013
SO PEDIATRICS
LA English
DT Article
ID OFF-LABEL; SURVEILLANCE; CHILDREN
AB BACKGROUND AND OBJECTIVES: In 2002, Congress mandated that the US Food and Drug Administration (FDA) monitor postmarketing pediatric adverse events and present safety reports to the FDA's Pediatric Advisory Committee (PAC). These safety reviews play a critical role in the postmarketing surveillance and identification of pediatric safety issues. This article follows a previous review ending in 2007 and summarizes 6 years of recent pediatric safety reporting, recommendations by the PAC, and actions by the FDA, including labeling changes.
METHODS: An analysis of the FDA's PAC safety reviews performed from November 2007 through September 2013 was conducted. PAC recommendations for subsequent labeling changes, future studies, or other safety issues were reviewed.
RESULTS: There were 6930 serious adverse event reports in 181 reviews. These findings resulted in 33 (18%) recommended labeling changes, and 21 (64%) of these changes were adopted. For 10 products, information was added to the Warning and Precautions section of the label. The PAC also discussed or recommended additional studies for certain products.
CONCLUSIONS: This article highlights the importance of the FDA's ongoing pediatric postmarketing safety reviews of regulated products, advice from the PAC, and FDA actions in the best interest of pediatric patients. This mandated process facilitates detection of safety concerns that may not be identified in prelicensure clinical trials. It continues to identify critical safety concerns, including unlabeled adverse events, frequent off-label use, product misuse, and secondary exposures in children.
C1 [Cope, Judith U.; Weinel, Pamela; Odegaard, Amy; Murphy, Dianne M.] US FDA, Off Special Med Programs, Off Commissioner, Off Pediat Therapeut, Silver Spring, MD USA.
[Rosenthal, Geoffrey L.] Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA.
RP Cope, JU (reprint author), US FDA, White Oak Bldg 32,Room 5156,10903 New Hampshire, Silver Spring, MD 20993 USA.
EM judith.cope@fda.hhs.gov
NR 11
TC 1
Z9 1
U1 2
U2 2
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD DEC
PY 2015
VL 136
IS 6
BP 1125
EP 1131
DI 10.1542/peds.2015-0469
PG 7
WC Pediatrics
SC Pediatrics
GA DD9OD
UT WOS:000370254400045
PM 26598453
ER
PT J
AU Philchenkov, AA
Zavelevich, MP
Tryndyak, VP
Kuiava, LM
Blokhin, DY
Miura, K
Silvestri, R
Pogribny, IP
AF Philchenkov, Alex A.
Zavelevich, Michael P.
Tryndyak, Volodymyr P.
Kuiava, Ludmila M.
Blokhin, Dmitry Yu
Miura, Koh
Silvestri, Romano
Pogribny, Igor P.
TI Antiproliferative and proapoptotic effects of a pyrrole containing
arylthioindole in human Jurkat leukemia cell line and
multidrug-resistant Jurkat/A4 cells
SO CANCER BIOLOGY & THERAPY
LA English
DT Article
DE apoptosis; arylthioindoles; drug resistance; gene expression; G(2)/M
arrest; Jurkat leukemia cells; microRNA
ID SEA-URCHIN EMBRYO; TUBULIN POLYMERIZATION; INDUCED APOPTOSIS; CANCER;
INHIBITORS; P53; ACTIVATION; EXPRESSION; LYMPHOMA; AGENTS
AB Recently, a series of novel arylthioindole compounds, potent inhibitors of tubulin polymerization and cancer cell growth, were synthesized. In the present study the effects of 2-(1H-pyrrol-3-yl)-3-((3,4,5-trimethoxyphenyl) thio)-1H-indole (ATI5 compound) on cell proliferation, cell cycle progression, and induction of apoptosis in human T-cell acute leukemia Jurkat cells and their multidrug resistant Jurkat/A4 subline were investigated. Treatment of the Jurkat cells with the ATI5 compound for 48 hrs resulted in a strong G(2)/M cell cycle arrest and p53-independent apoptotic cell death accompanied by the induction of the active form of caspase-3 and poly(ADP-ribose) polymerase-1 (PARP-1) cleavage. ATI5 treatment also caused non-cell death related mitotic arrest in multidrug resistant Jurkat/A4 cells after 48 hrs of treatment suggesting promising opportunities for the further design of pyrrole-containing ATI compounds as anticancer agents. Cell death resistance of Jurkat/A4 cells to ATI5 compound was associated with alterations in the expression of pro-survival and anti-apoptotic protein-coding and microRNA genes. More importantly, findings showing that ATI5 treatment induced p53-independent apoptosis are of great importance from a therapeutic point of view since p53 mutations are common genetic alterations in human neoplasms.
C1 [Philchenkov, Alex A.; Zavelevich, Michael P.; Kuiava, Ludmila M.] Natl Acad Sci Ukraine, RE Kavetsky Inst Expt Oncol Pathol & Radiobiol, Kiev, Ukraine.
[Zavelevich, Michael P.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
[Blokhin, Dmitry Yu] NN Blokhin Canc Res Ctr, Moscow, Russia.
[Miura, Koh] Miyagi Canc Ctr, Natori, Miyagi 9811293, Japan.
[Silvestri, Romano] Univ Roma La Sapienza, Ist Pasteur, Fdn Cenci Bolognetti, I-00185 Rome, Italy.
RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
EM igor.pogribny@fda.hhs.gov
FU State Fund for Fundamental Research (DFFD), Ukraine [F53.4/056]
FX This work was partially supported by the Grant # F53.4/056 from State
Fund for Fundamental Research (DFFD), Ukraine.
NR 37
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U1 1
U2 2
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1538-4047
EI 1555-8576
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD DEC
PY 2015
VL 16
IS 12
BP 1820
EP 1829
DI 10.1080/15384047.2015.1078026
PG 10
WC Oncology
SC Oncology
GA DD4TS
UT WOS:000369916100016
PM 26785947
ER
PT J
AU Botticelli, MP
Brock, I
Brooks, P
Byram, D
Clark, KJ
Curro, FA
Daw, J
Duggan, M
Erensen, J
Fan, J
Francis, W
Gammitoni, A
Ghods, MP
Greenberg, P
Jan, SA
Jeffrey, PL
Kowalski, T
Lee, J
McNally, DL
Nowak, LE
Peppin, JF
Schroeder, A
Schmidt, P
Stoddard, J
Tanzman, B
Thomson, H
Wesolowicz, L
Dragovich, C
Eichelberger, B
Mackowiak, J
Oh, S
Sega, T
Singh, P
Singh, R
AF Botticelli, Michael P.
Brock, Irwin Pete, III
Brooks, Phyllis
Byram, David
Clark, Kelly J.
Curro, Frederick A.
Daw, Jessica
Duggan, Mike
Erensen, Jennifer
Fan, Jennifer
Francis, William
Gammitoni, Arnold
Ghods, Mary P.
Greenberg, Peggy
Jan, Saira A.
Jeffrey, Paul L.
Kowalski, Thomas
Lee, Jinhee
McNally, Diane L.
Nowak, Lynne E.
Peppin, John F.
Schroeder, Allie
Schmidt, Pete
Stoddard, Jeff
Tanzman, Beth
Thomson, Heather
Wesolowicz, Laurie
Dragovich, Charlie
Eichelberger, Bernadette
Mackowiak, John
Oh, Susan
Sega, Todd
Singh, Puneet
Singh, Ruby
TI Proceedings of the AMCP Partnership Forum: Breaking the Link Between
Pain Management and Opioid Use Disorder
SO JOURNAL OF MANAGED CARE & SPECIALTY PHARMACY
LA English
DT Article
ID UNITED-STATES
AB Prescription drug misuse and abuse, especially with opioid analgesics, is the fastest growing drug problem in the United States. Addressing this public health crisis demands the coordinated efforts and actions of all stakeholders to establish a process of improving patient care and decreasing misuse and abuse. On September 9, 2014, the Academy of Managed Care Pharmacy (AMCP) convened a meeting of multiple stakeholders to recommend activities and programs that AMCP can promote to improve pain management, prevent opioid use disorder (OUD), and improve medication assisted treatment outcomes.
The speakers and panelists recommended that efforts to improve pain management outcomes and reduce the potential for OUD should rely on demonstrated evidence and best practices. It was recommended that AMCP promote a more holistic and evidence-based approach to pain management and OUD treatment that actively engages the patient in the decision-making process and includes care coordination with medical, pharmacy, behavioral, and mental health aspects of organizations, all of which is seamlessly supported by a technology infrastructure. To accomplish this, it was recommended that AMCP work to collaborate with organizations representing these stakeholders. Additionally, it was recommended that AMCP conduct continuing pharmacy education programs, develop a best practices toolkit on pain management, and actively promote quality standards for OUD prevention and treatment. Copyright (C) 2015, Academy of Managed Care Pharmacy. All rights reserved.
C1 [Botticelli, Michael P.] Off Natl Drug Control Policy, London, England.
[Brock, Irwin Pete, III] Optum Hlth Behav Solut, Affordabil, New York, NY USA.
[Brooks, Phyllis] Humana, Drug Utilizat Review, Louisville, KY USA.
[Byram, David] Orexo, Market Access, Stockholm, Sweden.
[Clark, Kelly J.] CVS Hlth, Med Affairs, London, England.
[Curro, Frederick A.] PEARL Clin Translat Network, New York, NY USA.
[Curro, Frederick A.] NYU, New York, NY 10003 USA.
[Daw, Jessica] Univ Pittsburgh, Med Ctr, Clin Pharm, Pittsburgh, PA USA.
[Erensen, Jennifer] Purdue Pharma, Hlth Policy, Stamford, CT USA.
[Fan, Jennifer] SAMHSA Ctr Substance Abuse Prevent, Rockville, MD USA.
[Francis, William] Medlmpact, Pharm Management Serv, San Diego, CA USA.
[Gammitoni, Arnold] Zogenix, Med & Sci Affairs, Bloomsburg, PA USA.
[Ghods, Mary P.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Greenberg, Peggy] Peggy Greenberg Consulting & Training, Silver Spring, MD USA.
[Jan, Saira A.] State Univ, Rutgers, New Brunswick, NJ USA.
[Jan, Saira A.] Horizon BCBS New Jersey, Clin Pharm, Newark, NJ USA.
[Jeffrey, Paul L.] MassfHlth, Pharm, Boston, MA USA.
[Kowalski, Thomas] Blue Cross & Blue Shield Massachusetts, Clin Pharm, Boston, MA USA.
[Lee, Jinhee] SAMHSA Ctr Substance Abuse Treatment, Baltimore, MD USA.
[McNally, Diane L.] Ctr Medicare, Baltimore, MD USA.
[McNally, Diane L.] Ctr Medicaid Serv, Baltimore, MD USA.
[Nowak, Lynne E.] Express Scripts, London, England.
[Peppin, John F.] Mallinchrodt, Global Med Affairs, Dublin, Ireland.
[Schroeder, Allie] Univ Colorado, Skaggs Sch Pharm, Kaiser Permanente Colorado, Boulder, CO USA.
[Schmidt, Pete] Depomed, Newark, CA USA.
[Stoddard, Jeff] Alkermes, Med Profess Serv, London, England.
[Tanzman, Beth] Vermont Blueprint Hlth, Waterbury, VT USA.
[Thomson, Heather] Kaleo, Managed Care, Austin, TX USA.
[Wesolowicz, Laurie] BCBS Michigan, Pharm Serv Clin, Detroit, MI USA.
[Dragovich, Charlie] Business Development, Sao Paulo, Brazil.
[Eichelberger, Bernadette] Pharm Affairs, Rio De Janeiro, Brazil.
[Mackowiak, John] Journal Managed Care & Specialty Pharm, Rio De Janeiro, Brazil.
[Oh, Susan; Sega, Todd] Pharm Affairs, Lagos, Nigeria.
[Singh, Puneet; Singh, Ruby] Educ, Brasilia, DF, Brazil.
RP Oh, S (reprint author), Acad Managed Care Pharm, Pharm Affairs, 100 N Pitt St,Ste 400, Alexandria, VA 22314 USA.
EM soh@amcp.org
FU Alkermes; Depomed; kaleo; Mallinckrodt; Orexo; Purdue Pharma; Teva;
Zogemx
FX The AMCP Partnership Forum on Breaking the Link Between Pain Management
and Opioid Use Disorder and the development of this proceedings document
were supported by Alkermes, Depomed, kaleo, Mallinckrodt, Orexo, Purdue
Pharma, Teva, and Zogemx.
NR 24
TC 0
Z9 0
U1 1
U2 1
PU ACAD MANAGED CARE PHARMACY
PI ALEXANDRIA
PA 100 N PITT ST, 400, ALEXANDRIA, VA 22314-3134 USA
SN 2376-0540
EI 2376-1032
J9 J MANAG CARE SPEC PH
JI J. Manag. Care Spec. Pharm.
PD DEC
PY 2015
VL 21
IS 12
BP 1116
EP 1122
PG 7
WC Health Care Sciences & Services; Pharmacology & Pharmacy
SC Health Care Sciences & Services; Pharmacology & Pharmacy
GA DC6UW
UT WOS:000369356100003
ER
PT J
AU Zhang, WQ
Ng, HW
Shu, M
Luo, H
Su, ZQ
Ge, WG
Perkins, R
Tong, WD
Hong, HX
AF Zhang, Wenqian
Ng, Hui Wen
Shu, Mao
Luo, Heng
Su, Zhenqiang
Ge, Weigong
Perkins, Roger
Tong, Weida
Hong, Huixiao
TI Comparing genetic variants detected in the 1000 genomes project with
SNPs determined by the International HapMap Consortium
SO JOURNAL OF GENETICS
LA English
DT Article
DE heterozygous rate; minor allele frequency; transition; transversion;
genotype discordance; genomewide association studies
ID WIDE ASSOCIATION; PERSONALIZED MEDICINE; MISSING HERITABILITY; COMMON
DISEASE; ARCHITECTURE; SEQUENCES; SPECTRUM; MUTATION; TRAITS; RATES
AB Single-nucleotide polymorphisms (SNPs) determined based on SNP arrays from the international HapMap consortium (HapMap) and the genetic variants detected in the 1000 genomes project (1KGP) can serve as two references for genomewide association studies (GWAS). We conducted comparative analyses to provide a means for assessing concerns regarding SNP array-based GWAS findings as well as for realistically bounding expectations for next generation sequencing (NGS)-based GWAS. We calculated and compared base composition, transitions to transversions ratio, minor allele frequency and heterozygous rate for SNPs from HapMap and 1KGP for the 622 common individuals. We analysed the genotype discordance between HapMap and 1KGP to assess consistency in the SNPs from the two references. In 1KGP, 90.58% of 36,817,799 SNPs detected were not measured in HapMap. More SNPs with minor allele frequencies less than 0.01 were found in 1KGP than HapMap. The two references have low discordance (generally smaller than 0.02) in genotypes of common SNPs, with most discordance from heterozygous SNPs. Our study demonstrated that SNP array-based GWAS findings were reliable and useful, although only a small portion of genetic variances were explained. NGS can detect not only common but also rare variants, supporting the expectation that NGS-based GWAS will be able to incorporate a much larger portion of genetic variance than SNP arrays-based GWAS.
C1 [Zhang, Wenqian; Ng, Hui Wen; Shu, Mao; Luo, Heng; Ge, Weigong; Perkins, Roger; Tong, Weida; Hong, Huixiao] US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
[Su, Zhenqiang] Thomson Reuters, IP & Sci, Boston, MA 02210 USA.
RP Hong, HX (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM huixiao.hong@fda.hhs.gov
NR 48
TC 2
Z9 4
U1 0
U2 12
PU INDIAN ACAD SCIENCES
PI BANGALORE
PA C V RAMAN AVENUE, SADASHIVANAGAR, P B #8005, BANGALORE 560 080, INDIA
SN 0022-1333
EI 0973-7731
J9 J GENET
JI J. Genet.
PD DEC
PY 2015
VL 94
IS 4
BP 731
EP 740
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA DC8WG
UT WOS:000369499900022
PM 26690529
ER
PT J
AU Sullivan, DC
Obuchowski, NA
Kessler, LG
Raunig, DL
Gatsonis, C
Huang, EP
Kondratovich, M
McShane, LM
Reeves, AP
Barboriak, DP
Guimaraes, AR
Wahl, RL
AF Sullivan, Daniel C.
Obuchowski, Nancy A.
Kessler, Larry G.
Raunig, David L.
Gatsonis, Constantine
Huang, Erich P.
Kondratovich, Marina
McShane, Lisa M.
Reeves, Anthony P.
Barboriak, Daniel P.
Guimaraes, Alexander R.
Wahl, Richard L.
CA RSNA-QIBA Metrol Working Grp
TI Metrology Standards for Quantitative Imaging Biomarkers
SO RADIOLOGY
LA English
DT Article
ID STATISTICAL-METHODS; TECHNICAL PERFORMANCE; GOLD STANDARD; LUNG-CANCER;
REPRODUCIBILITY; AGREEMENT; PET; ISSUES
AB Although investigators in the imaging community have been active in developing and evaluating quantitative imaging biomarkers (QIBs), the development and implementation of QIBs have been hampered by the inconsistent or incorrect use of terminology or methods for technical performance and statistical concepts. Technical performance is an assessment of how a test performs in reference objects or subjects under controlled conditions. In this article, some of the relevant statistical concepts are reviewed, methods that can be used for evaluating and comparing QIBs are described, and some of the technical performance issues related to imaging biomarkers are discussed. More consistent and correct use of terminology and study design principles will improve clinical research, advance regulatory science, and foster better care for patients who undergo imaging studies. (C)RSNA, 2015
C1 [Sullivan, Daniel C.; Barboriak, Daniel P.] Duke Univ, Med Ctr, Dept Radiol, Box 2715, Durham, NC 27710 USA.
[Obuchowski, Nancy A.] Cleveland Clin Fdn, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA.
[Kessler, Larry G.] Univ Washington, Dept Publ Hlth, Seattle, WA 98195 USA.
[Raunig, David L.] ICON Med, Dept Informat, Washington, PA USA.
[Gatsonis, Constantine] Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA.
[Huang, Erich P.; McShane, Lisa M.] NCI, Bethesda, MD 20892 USA.
[Kondratovich, Marina] US FDA, Ctr Devices & Radiol Hlth, White Oak, MD USA.
[Reeves, Anthony P.] Cornell Univ, Dept Elect & Comp Engn, Ithaca, NY USA.
[Guimaraes, Alexander R.] Oregon Hlth & Sci Univ, Dept Radiol, Portland, OR 97201 USA.
[Wahl, Richard L.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA.
RP Sullivan, DC (reprint author), Duke Univ, Med Ctr, Dept Radiol, Box 2715, Durham, NC 27710 USA.
EM daniel.sullivan@duke.edu
FU National Institutes of Health [HHSN268201000050C]
FX This research was supported by the National Institutes of Health (grant
no. HHSN268201000050C).
NR 31
TC 19
Z9 19
U1 3
U2 8
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD DEC
PY 2015
VL 277
IS 3
BP 813
EP 825
DI 10.1148/radiol.2015142202
PG 13
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DC9EY
UT WOS:000369525100021
PM 26267831
ER
PT J
AU Cafri, G
Banerjee, S
Sedrakyan, A
Paxton, L
Furnes, O
Graves, S
Marinac-Dabic, D
AF Cafri, Guy
Banerjee, Samprit
Sedrakyan, Art
Paxton, Liz
Furnes, Ove
Graves, Stephen
Marinac-Dabic, Danica
TI Meta-analysis of survival curve data using distributed health data
networks: application to hip arthroplasty studies of the International
Consortium of Orthopaedic Registries
SO RESEARCH SYNTHESIS METHODS
LA English
DT Article
DE survival; ICOR; mixed models; multivariate meta-analysis
ID REGRESSION; OUTCOMES; MODEL
AB The motivating example for this paper comes from a distributed health data network, the International Consortium of Orthopaedic Registries (ICOR), which aims to examine risk factors for orthopedic device failure for registries around the world. Unfortunately, regulatory, privacy, and propriety concerns made sharing of raw data impossible, even if de-identified. Therefore, this article describes an approach to extraction and analysis of aggregate time-to-event data from ICOR. Data extraction is based on obtaining a survival probability and variance estimate for each unique combination of the explanatory variables at each distinct event time for each registry. The extraction procedure allows for a great deal of flexibility; models can be specified after the data have been collected, for example, modeling of interaction effects and selection of subgroups of patients based on their values on the explanatory variables. Our analysis models are adapted from models presented elsewhere - but allowing for censoring in the calculation of the correlation between serial survival probabilities and using the square root of the covariance matrix to transform the data to avoid computational problems in model estimation. Simulations and a real-data example are provided with strengths and limitations of the approach discussed. Copyright (c) 2015 John Wiley & Sons, Ltd.
C1 [Cafri, Guy; Paxton, Liz] Kaiser Permanente, Surg Outcomes & Anal, Oakland, CA USA.
[Cafri, Guy] Univ Calif San Diego, Dept Psychiat, San Diego, CA USA.
[Banerjee, Samprit; Sedrakyan, Art] Weill Cornell Med Coll, Dept Healthcare Policy & Res, New York, NY USA.
[Furnes, Ove] Haukeland Hosp, Dept Orthopaed Surg, Norwegian Arthroplasty Register, N-5021 Bergen, Norway.
[Furnes, Ove] Univ Bergen, Dept Surg Sci, Bergen, Norway.
[Furnes, Ove] Univ Bergen, Fac Med, Locus Registry Based Epidemiol, Bergen, Norway.
[Graves, Stephen] Australian Orthopaed Assoc Natl Joint Replacement, Adelaide, SA, Australia.
[Marinac-Dabic, Danica] FDA, Ctr Device & Radiol Hlth, Off Surveillance & Biometr, Silver Spring, MD USA.
RP Cafri, G (reprint author), Kaiser Permanente, SCPMG Clin Anal Dept, Surg Outcomes & Anal Unit, 3840 Murphy Canyon Rio,Suite 406, San Diego, CA 92123 USA.
EM guycafri@gmail.com
RI Graves, Stephen/A-9463-2016
OI Graves, Stephen/0000-0002-1629-319X
FU Food and Drug Administration, MD, USA [HHSF223201110172C]
FX The ICOR initiative including the coordinating center at Cornell and
Kaiser Permanente is funded by a contract HHSF223201110172C (PI,
Sedrakyan) from the Food and Drug Administration, MD, USA.
NR 25
TC 0
Z9 0
U1 2
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1759-2879
EI 1759-2887
J9 RES SYNTH METHODS
JI Res. Synth. Methods
PD DEC
PY 2015
VL 6
IS 4
BP 347
EP 356
DI 10.1002/jrsm.1159
PG 10
WC Mathematical & Computational Biology; Multidisciplinary Sciences
SC Mathematical & Computational Biology; Science & Technology - Other
Topics
GA DB9UE
UT WOS:000368861600004
PM 26123233
ER
PT J
AU Pezeshk, A
Sahiner, B
Zeng, RP
Wunderlich, A
Chen, WJ
Petrick, N
AF Pezeshk, Aria
Sahiner, Berkman
Zeng, Rongping
Wunderlich, Adam
Chen, Weijie
Petrick, Nicholas
TI Seamless Insertion of Pulmonary Nodules in Chest CT Images
SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
LA English
DT Article
DE Data augmentation; image composition; Poisson editing; pulmonary nodules
ID COMPUTER-AIDED DIAGNOSIS; FINITE-SAMPLE SIZE; LUNG NODULES; DATABASE
CONSORTIUM; PATTERN-RECOGNITION; PERFORMANCE; SIMULATION; RADIOLOGISTS;
TOMOGRAPHY; ALGORITHM
AB The availability of large medical image datasets is critical in many applications, such as training and testing of computer-aided diagnosis systems, evaluation of segmentation algorithms, and conducting perceptual studies. However, collection of data and establishment of ground truth for medical images are both costly and difficult. To address this problem, we are developing an image blending tool that allows users to modify or supplement existing datasets by seamlessly inserting a lesion extracted from a source image into a target image. In this study, we focus on the application of this tool to pulmonary nodules in chest CT exams. We minimize the impact of user skill on the perceived quality of the composite image by limiting user involvement to two simple steps: the user first draws a casual boundary around a nodule in the source, and, then, selects the center of desired insertion area in the target. We demonstrate the performance of our system on clinical samples, and report the results of a reader study evaluating the realism of inserted nodules compared to clinical nodules. We further evaluate our image blending techniques using phantoms simulated under different noise levels and reconstruction filters. Specifically, we compute the area under the ROC curve of the Hotelling observer (HO) and noise power spectrum of regions of interest enclosing native and inserted nodules, and compare the detectability, noise texture, and noise magnitude of inserted and native nodules. Our results indicate the viability of our approach for insertion of pulmonary nodules in clinical CT images.
C1 [Pezeshk, Aria] US FDA, Div Imaging Diagnost & Software Reliabil, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Sahiner, Berkman; Zeng, Rongping; Wunderlich, Adam; Chen, Weijie; Petrick, Nicholas] US FDA, Silver Spring, MD 20993 USA.
RP Pezeshk, A (reprint author), US FDA, Div Imaging Diagnost & Software Reliabil, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
EM aria.pezeshk@fda.hhs.gov
OI PEZESHK, ARIA/0000-0002-3570-3051
FU Critical Path grant and an Office of Women's Health grant from U.S. Food
and Drug Administration
FX The work of A. Pezeshk was supported in part through a Critical Path
grant and an Office of Women's Health grant from the U.S. Food and Drug
Administration, and by an appointment to the Research Participation
Program at the Center for Devices and Radiological Health administered
by the Oak Ridge Institute for Science and Education through an
interagency agreement between the U.S. Department of Energy and the U.S.
Food and Drug Administration.
NR 53
TC 1
Z9 1
U1 2
U2 5
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0018-9294
EI 1558-2531
J9 IEEE T BIO-MED ENG
JI IEEE Trans. Biomed. Eng.
PD DEC
PY 2015
VL 62
IS 12
SI SI
BP 2812
EP 2827
DI 10.1109/TBME.2015.2445054
PG 16
WC Engineering, Biomedical
SC Engineering
GA DB3NV
UT WOS:000368419300007
PM 26080378
ER
PT J
AU Ghassemi, P
Wang, JT
Melchiorri, AJ
Ramella-Roman, JC
Mathews, SA
Coburn, JC
Sorg, BS
Chen, Y
Pfefer, TJ
AF Ghassemi, Pejhman
Wang, Jianting
Melchiorri, Anthony J.
Ramella-Roman, Jessica C.
Mathews, Scott A.
Coburn, James C.
Sorg, Brian S.
Chen, Yu
Pfefer, T. Joshua
TI Rapid prototyping of biomimetic vascular phantoms for hyperspectral
reflectance imaging
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE three-dimensional printing; tissue phantoms; hyperspectral reflectance
imaging; oximetry
ID TISSUE OPTICAL-PROPERTIES; TURBID MEDIA; IN-VITRO; SATURATION
AB The emerging technique of rapid prototyping with three-dimensional (3-D) printers provides a simple yet revolutionary method for fabricating objects with arbitrary geometry. The use of 3-D printing for generating morphologically biomimetic tissue phantoms based on medical images represents a potentially major advance over existing phantom approaches. Toward the goal of image-defined phantoms, we converted a segmented fundus image of the human retina into a matrix format and edited it to achieve a geometry suitable for printing. Phantoms with vessel-simulating channels were then printed using a photoreactive resin providing biologically relevant turbidity, as determined by spectrophotometry. The morphology of printed vessels was validated by x-ray microcomputed tomography. Channels were filled with hemoglobin (Hb) solutions undergoing desaturation, and phantoms were imaged with a near-infrared hyperspectral reflectance imaging system. Additionally, a phantom was printed incorporating two disjoint vascular networks at different depths, each filled with Hb solutions at different saturation levels. Light propagation effects noted during these measurements-including the influence of vessel density and depth on Hb concentration and saturation estimates, and the effect of wavelength on vessel visualization depth-were evaluated. Overall, our findings indicated that 3-D-printed biomimetic phantoms hold significant potential as realistic and practical tools for elucidating light-tissue interactions and characterizing biophotonic system performance. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License.
C1 [Ghassemi, Pejhman; Wang, Jianting; Coburn, James C.; Pfefer, T. Joshua] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Wang, Jianting; Melchiorri, Anthony J.; Chen, Yu] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA.
[Ramella-Roman, Jessica C.] Florida Int Univ, Dept Biomed Engn, Miami, FL 33174 USA.
[Ramella-Roman, Jessica C.] Florida Int Univ, Herbert Wertheim Coll Med, Miami, FL 33174 USA.
[Mathews, Scott A.] Catholic Univ Amer, Dept Elect Engn & Comp Sci, Washington, DC 20064 USA.
[Sorg, Brian S.] NCI, NIH, Rockville, MD 20852 USA.
RP Pfefer, TJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM Joshua.Pfefer@fda.hhs.gov
FU Food and Drug Administration (FDA) Critical Path Initiative; National
Science Foundation's FDA Scholar-in-Residence program (NSF)
[CBET-1238407]; University of Maryland's Center for Excellence in
Regulatory Science and Innovation
FX The authors would like to thank Dr. Srinidhi Nagaraja, Dr. Maureen
Dreher, and Dr. Maria Iacono for their help with mu-CT imaging and 3-D
visualization. The authors gratefully acknowledge funding support from
the Food and Drug Administration (FDA) Critical Path Initiative, the
National Science Foundation's FDA Scholar-in-Residence program (NSF,
CBET-1238407), and the University of Maryland's Center for Excellence in
Regulatory Science and Innovation.
NR 29
TC 2
Z9 2
U1 1
U2 5
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
EI 1560-2281
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD DEC
PY 2015
VL 20
IS 12
AR 121312
DI 10.1117/1.JBO.20.12.121312
PG 10
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA DB3VG
UT WOS:000368440300015
PM 26662064
ER
PT J
AU U-Thainual, P
Kim, DH
AF U-Thainual, Paweena
Kim, Do-Hyun
TI Comparison between optical-resolution photoacoustic microscopy and
confocal laser scanning microscopy for turbid sample imaging
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE photoacoustic microscopy; confocal microscopy; lateral resolution;
turbid media; Monte Carlo simulation
ID MEDIA
AB Optical-resolution photoacoustic microscopy (ORPAM) in theory provides lateral resolution equivalent to the optical diffraction limit. Scattering media, such as biological turbid media, attenuates the optical signal and also alters the diffraction-limited spot size of the focused beam. The ORPAM signal is generated only from a small voxel in scattering media with dimensions equivalent to the laser spot size after passing through scattering layers and is detected by an acoustic transducer, which is not affected by optical scattering. Thus, both ORPAM and confocal laser scanning microscopy (CLSM) reject scattered light. A multimodal optical microscopy platform that includes ORPAM and CLSM was constructed, and the lateral resolution of both modes was measured using patterned thin metal film with and without a scattering barrier. The effect of scattering media on the lateral resolution was studied using different scattering coefficients and was compared to computational results based on Monte Carlo simulations. It was found that degradation of lateral resolution due to optical scattering was not significant for either ORPAM or CLSM. The depth discrimination capability of ORPAM and CLSM was measured using microfiber embedded in a light scattering phantom material. ORPAM images demonstrated higher contrast compared to CLSM images partly due to reduced acoustic signal scattering. (C) 2015 Society of Photo-Optical Instrumentation Engineers (SPIE)
C1 [U-Thainual, Paweena; Kim, Do-Hyun] US FDA, Silver Spring, MD 20993 USA.
RP Kim, DH (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM do-hyun.kim@fda.hhs.gov
FU Medical Countermeasures Initiative of the U.S. Food and Drug
Administration
FX This work was supported in part by the Medical Countermeasures
Initiative of the U.S. Food and Drug Administration. The mention of
commercial products, their sources, or their use in connection with
material reported herein is not to be construed as either an actual or
implied endorsement of such products by the Department of Health and
Human Services.
NR 22
TC 1
Z9 1
U1 1
U2 34
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
EI 1560-2281
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD DEC
PY 2015
VL 20
IS 12
AR 121202
DI 10.1117/1.JBO.20.12.121202
PG 9
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA DB3VG
UT WOS:000368440300003
PM 26256640
ER
PT J
AU Ekezue, BF
Sridhar, G
Ovanesov, MV
Forshee, RA
Izurieta, HS
Selvam, N
Parunov, LA
Jain, N
Mintz, PD
Epstein, JS
Anderson, SA
Menis, MD
AF Ekezue, B. F.
Sridhar, G.
Ovanesov, M. V.
Forshee, R. A.
Izurieta, H. S.
Selvam, N.
Parunov, L. A.
Jain, N.
Mintz, P. D.
Epstein, J. S.
Anderson, S. A.
Menis, M. D.
TI Clotting factor product administration and same-day occurrence of
thrombotic events, as recorded in a large healthcare database during
2008-2013
SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS
LA English
DT Article
DE clotting factors; healthcare; laboratory; risk factors; thrombosis
ID ACTIVATED FACTOR-VII; PROTHROMBIN COMPLEX CONCENTRATE; RECOMBINANT
FACTOR-VIIA; THROMBOEMBOLIC ADVERSE EVENTS; VON-WILLEBRAND DISEASE;
FACTOR-IX; BLEEDING DISORDERS; HEMOPHILIA-A; SAFETY; COAGULATION
AB Background: Thrombotic events (TEs) are serious adverse events that can occur following administration of clotting factors (CFs). Objectives: To evaluate occurrence of same-day TEs for different CF products and potential risk factors. Methods: A retrospective cohort study of individuals exposed to CF products during 2008-2013 was conducted using a large commercial insurance database. CF products were identified by procedure codes, and TEs were ascertained via diagnosis codes. Crude same-day TE rates (per 1000 persons exposed) were estimated overall and by congenital factor deficiency (CFD) status, CF products, age and gender. Multivariable logistic regression analyses were used to control for confounding. Laboratory analysis was used to compare the procoagulant activities of FIX products. Results: Of 3801 individuals exposed to CFs, 117 (30.8 per 1000) had same-day TEs recorded. The crude same-day TE rate was higher for CF users without CFD, 70.2 (102 of 1452), as compared with those with CFD, 6.4 (15 of 2349) (RR, 11.0; 95% CI, 6.4-18.9). For individuals without CFD, a significantly increased same-day TE risk was identified for factor IX complex (OR, 6.92; 95% CI, 3.11-15.40), factor VIIa (OR, 9.42; 95% CI, 4.9917.78) and other products when compared with fibrin sealant. An increased risk of a TE was found with older age (>= 45 years), history of TEs and underlying health conditions. The laboratory identified elevated procoagulant activity in Profilnine (R) and Benefix (R). Conclusions: The study shows an increased same-day TE risk for CF users without CFD and suggests substantial off-label CF use. The study findings also show elevated same-day TE rates for different CF products and suggest the importance of product properties and patient factors.
C1 [Ekezue, B. F.; Sridhar, G.; Selvam, N.] HealthCore Inc, Silver Spring, MD USA.
[Ovanesov, M. V.; Forshee, R. A.; Izurieta, H. S.; Parunov, L. A.; Jain, N.; Mintz, P. D.; Epstein, J. S.; Anderson, S. A.; Menis, M. D.] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
RP Ekezue, BF (reprint author), HealthCore Inc, 2001 N Beauregard St,Suite 500, Alexandria, VA 22311 USA.
EM bekezue@healthcore.com
FU US Food and Drug Administration, Center for Biologics Evaluation and
Research
FX The authors thank Renata Moldavskaya for her contribution in editing
drafts of the manuscript. This study was funded by the US Food and Drug
Administration, Center for Biologics Evaluation and Research. This paper
is an informal communication and represents the authors' best judgment.
It does not bind or obligate the US Food and Drug Administration.
NR 50
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Z9 6
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1538-7933
EI 1538-7836
J9 J THROMB HAEMOST
JI J. Thromb. Haemost.
PD DEC
PY 2015
VL 13
IS 12
BP 2168
EP 2179
DI 10.1111/jth.13155
PG 12
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA DB3VA
UT WOS:000368439700007
PM 26414338
ER
PT J
AU Kaufman, AR
Land, S
Parascandola, M
Augustson, E
Backinger, CL
AF Kaufman, Annette R.
Land, Stephanie
Parascandola, Mark
Augustson, Erik
Backinger, Cathy L.
TI Tobacco use transitions in the United States: The National Longitudinal
Study of Adolescent Health
SO PREVENTIVE MEDICINE
LA English
DT Article
DE Adolescent; Tobacco; Smoking; Smokeless; Tobacco; National Longitudinal
Study of Adolescent Health
ID HIGH-SCHOOL-STUDENTS; SMOKELESS TOBACCO; CIGARETTE-SMOKING; PRODUCT USE;
POLYTOBACCO USE; RISK-FACTOR; PANEL-DATA; ADULTS; PREVALENCE; PREDICTORS
AB Objectives. The purpose of this study is to evaluate and describe transitions in cigarette and smokeless tobacco (ST) use, including dual use, prospectively from adolescence into young adulthood. Methods. The current study utilizes four waves of the National Longitudinal Study of Adolescent Health (Add Health) to examine patterns of cigarette and ST use (within 30 days of survey) over time among a cohort in the United States beginning in 7th-12th grade (1995) into young adulthood (2008-2009). Transition probabilities were estimated using Markov modeling. Results. Among the cohort (N = 20,774), 48.7% reported using cigarettes, 12.8% reported using ST, and 7.2% reported dual use (cigarettes and ST in the same wave) in at least one wave. In general, the risk for transitioning between cigarettes and ST was higher for males and those who were older. Dual users exhibited a high probability (81%) of continuing dual use over time. Conclusions. Findings suggest that adolescents who use multiple tobacco products are likely to continue such use as they move into young adulthood. When addressing tobacco use among adolescents and young adults, multiple forms of tobacco use should be considered. Published by Elsevier Inc.
C1 [Kaufman, Annette R.; Land, Stephanie; Parascandola, Mark; Augustson, Erik] NCI, Tobacco Control Res Branch, Rockville, MD 20850 USA.
[Backinger, Cathy L.] US FDA, Ctr Tobacco Prod, Silver Spring, MD USA.
RP Kaufman, AR (reprint author), NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, 9609 Med Ctr Dr,3-E-546, Rockville, MD 20850 USA.
EM kaufmana@mail.nih.gov
FU National Cancer Institute; Eunice Kennedy Shriver National Institute of
Child Health and Human Development [P01-HD31921]
FX This work was supported by the National Cancer Institute. This research
uses data from Add Health, a program project directed by Kathleen Mullan
Harris and designed by J. Richard Udry, Peter S. Bearman, and Kathleen
Mullan Harris at the University of North Carolina at Chapel Hill, and
funded by grant P01-HD31921 from the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, with cooperative
funding from 23 other federal agencies and foundations. Special
acknowledgment is due Ronald R. Rindfuss and Barbara Entwisle for
assistance in the original design. Information on how to obtain the Add
Health data files is available on the Add Health website
(http://www.cpc.unc.edu/addhealth). No direct support was received from
grant P01-HD31921 for this analysis.
NR 45
TC 2
Z9 2
U1 1
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-7435
EI 1096-0260
J9 PREV MED
JI Prev. Med.
PD DEC
PY 2015
VL 81
BP 251
EP 257
DI 10.1016/j.ypmed.2015.08.026
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA DB3OP
UT WOS:000368421300038
PM 26361752
ER
PT J
AU Chung, SM
Lee, DJ
Hand, A
Young, P
Vaidyanathan, J
Sahajwalla, C
AF Chung, Sang M.
Lee, David J.
Hand, Austin
Young, Philip
Vaidyanathan, Jayabharathi
Sahajwalla, Chandrahas
TI Kidney function changes with aging in adults: comparison between
cross-sectional and longitudinal data analyses in renal function
assessment
SO BIOPHARMACEUTICS & DRUG DISPOSITION
LA English
DT Article
DE renal function decline rates; cross-sectional analysis; longitudinal
analysis
ID GLOMERULAR-FILTRATION-RATE; CREATININE CLEARANCE; SERUM CREATININE; AGE;
PREDICTION; DECLINE; DISEASE
AB The study evaluated whether the renal function decline rate per year with age in adults varies based on two primary statistical analyses: cross-section (CS), using one observation per subject, and longitudinal (LT), using multiple observations per subject over time. A total of 16628 records (3946 subjects; age range 30-92 years) of creatinine clearance and relevant demographic data were used. On average, four samples per subject were collected for up to 2364 days (mean: 793 days). A simple linear regression and random coefficient models were selected for CS and LT analyses, respectively. The renal function decline rates per year were 1.33 and 0.95 ml/min/year for CS and LT analyses, respectively, and were slower when the repeated individual measurements were considered. The study confirms that rates are different based on statistical analyses, and that a statistically robust longitudinal model with a proper sampling design provides reliable individual as well as population estimates of the renal function decline rates per year with age in adults. In conclusion, our findings indicated that one should be cautious in interpreting the renal function decline rate with aging information because its estimation was highly dependent on the statistical analyses. From our analyses, a population longitudinal analysis (e.g. random coefficient model) is recommended if individualization is critical, such as a dose adjustment based on renal function during a chronic therapy. Copyright (C) 2015 John Wiley & Sons, Ltd.
C1 [Chung, Sang M.; Lee, David J.; Vaidyanathan, Jayabharathi; Sahajwalla, Chandrahas] US FDA, OCP, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Hand, Austin] Quintiles, Austin, TX USA.
[Young, Philip] Baylor Univ, Waco, TX 76798 USA.
RP Chung, SM (reprint author), US FDA, OCP, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
EM sang.chung@fda.hhs.gov
NR 14
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0142-2782
EI 1099-081X
J9 BIOPHARM DRUG DISPOS
JI Biopharm. Drug Dispos.
PD DEC
PY 2015
VL 36
IS 9
BP 613
EP 621
DI 10.1002/bdd.1988
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DB1KZ
UT WOS:000368268400005
PM 26301459
ER
PT J
AU Husain, SR
Han, J
Au, P
Shannon, K
Puri, RK
AF Husain, S. R.
Han, J.
Au, P.
Shannon, K.
Puri, R. K.
TI Gene therapy for cancer: regulatory considerations for approval
SO CANCER GENE THERAPY
LA English
DT Review
ID ADENOASSOCIATED VIRUS AAV; CYSTIC-FIBROSIS; VECTORS
AB The rapidly changing field of gene therapy promises a number of innovative treatments for cancer patients. Advances in genetic modification of cancer and immune cells and the use of oncolytic viruses and bacteria have led to numerous clinical trials for cancer therapy, with several progressing to late-stage product development. At the time of this writing, no gene therapy product has been approved by the United States Food and Drug Administration (FDA). Some of the key scientific and regulatory issues include understanding of gene transfer vector biology, safety of vectors in vitro and in animal models, optimum gene transfer, long-term persistence or integration in the host, shedding of a virus and ability to maintain transgene expression in vivo for a desired period of time. Because of the biological complexity of these products, the FDA encourages a flexible, data-driven approach for preclinical safety testing programs. The clinical trial design should be based on the unique features of gene therapy products, and should ensure the safety of enrolled subjects. This article focuses on regulatory considerations for gene therapy product development and also discusses guidance documents that have been published by the FDA.
C1 [Husain, S. R.; Han, J.; Puri, R. K.] US FDA, Div Cellular & Gene Therapies, CBER, Silver Spring, MD 20993 USA.
[Au, P.; Shannon, K.] US FDA, Div Clin Evaluat & Pharmacol Toxicol, CBER, Silver Spring, MD 20993 USA.
RP Puri, RK (reprint author), US FDA, Div Cellular & Gene Therapies, CBER, 10903 New Hampshire Ave,WO71,Room 5342, Silver Spring, MD 20993 USA.
EM syed.husain@fda.hhs.gov; raj.puri@fda.hhs.gov
NR 34
TC 4
Z9 4
U1 1
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0929-1903
EI 1476-5500
J9 CANCER GENE THER
JI Cancer Gene Ther.
PD DEC
PY 2015
VL 22
IS 12
BP 554
EP 563
DI 10.1038/cgt.2015.58
PG 10
WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity;
Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity;
Research & Experimental Medicine
GA DA9ZI
UT WOS:000368167900002
PM 26584531
ER
PT J
AU Ribeiro-Gomes, FL
Romano, A
Lee, S
Roffe, E
Peters, NC
Debrabant, A
Sacks, D
AF Ribeiro-Gomes, F. L.
Romano, A.
Lee, S.
Roffe, E.
Peters, N. C.
Debrabant, A.
Sacks, D.
TI Apoptotic cell clearance of Leishmania major-infected neutrophils by
dendritic cells inhibits CD8(+) T-cell priming in vitro by Mer tyrosine
kinase-dependent signaling
SO CELL DEATH & DISEASE
LA English
DT Article
ID TOXOPLASMA-GONDII INFECTION; SAND FLIES; MACROPHAGES; ANTIGEN;
PHAGOCYTOSIS; TUBERCULOSIS; ACTIVATION; PROTEIN; DEATH; MICE
AB Neutrophils are the predominant recruited and infected cells during the early stages of Leishmania major infection in the skin, and depletion of neutrophils promotes immunity to infection transmitted by sand fly bite. In order to better understand how the acute neutrophilic response suppresses immunity, we assessed the consequences of the interaction between neutrophils recovered from the skin-inoculation site and bone marrow-derived dendritic cells (DCs) in vitro. The capture of infected, apoptotic neutrophils by the DCs completely inhibited their cross-presentation function that was dependent on engagement of the receptor tyrosine kinase Mer on the DCs. The capture of uninfected neutrophils, or neutrophils infected with Toxoplasma gondii, had only slight immunomodulatory effects. These studies define the clearance of infected, apoptotic neutrophils by DCs and Mer receptor signaling as central to the early immune evasion strategies of L. major, with relevance to other vector-borne pathogens delivered by bite to the skin.
C1 [Ribeiro-Gomes, F. L.; Romano, A.; Lee, S.; Peters, N. C.; Sacks, D.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Roffe, E.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Debrabant, A.] US FDA, OBRR, CBER, Silver Spring, MD USA.
RP Sacks, D (reprint author), NIAID, Parasit Dis Lab, Bldg 4,Room B1-12,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA.
EM dsacks@nih.gov
RI Roffe, Ester/H-4688-2012
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX We thank M Grigg and V Pzsenny for provision of the T. gondii strain,
and C Rothlin and J Coligan for donation of the Mer-/- and
CD300f-/- mice, respectively. We thank Kim Beacht for
assistance with the animal studies. We thank T Moyer, C Henry, E
Stregevsky and B Hague for cell sorting and S Ganesan for technical
assistance with the confocal microscopy. This work was supported in part
by the Intramural Research Program of the National Institute of Allergy
and Infectious Diseases, National Institutes of Health.
NR 40
TC 7
Z9 7
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD DEC
PY 2015
VL 6
AR e2018
DI 10.1038/cddis.2015.351
PG 12
WC Cell Biology
SC Cell Biology
GA DB0BA
UT WOS:000368172400017
PM 26658192
ER
PT J
AU Churchwell, MI
Scheri, RC
Von Tungeln, LS
da Costa, GG
Beland, FA
Doerge, DR
AF Churchwell, M. I.
Scheri, R. C.
Von Tungeln, L. S.
da Costa, G. Gamboa
Beland, F. A.
Doerge, D. R.
TI Evaluation of serum and liver toxicokinetics for furan and liver DNA
adduct formation in male Fischer 344 rats
SO FOOD AND CHEMICAL TOXICOLOGY
LA English
DT Article
DE Furan; Hepatotoxicity; Hepatocarcinogen; Mass spectrometry;
Pharmacokinetics
ID GAS CHROMATOGRAPHY/MASS SPECTROMETRY; REACTIVE METABOLITE; F344 RATS;
IN-VIVO; EXPOSURE; GENOTOXICITY; CANCER; COFFEE; FOODS; ACID
AB Furan is a food processing contaminant found in many common cooked foods that induces liver toxicity and liver cancer in animal models treated with sufficient doses. The metabolism of furan occurs primarily in the liver where CYP 2E1 produces a highly reactive bis-electrophile, cis-2-butene-1,4-dial (BDA). BDA reacts with nucleophilic groups in amino acids and DNA in vitro to form covalent adducts. Evidence for BDA-nucleoside adduct formation in vivo is limited but important for assessing the carcinogenic hazard of dietary furan. This study used controlled dosing with furan in Fischer 344 rats to measure serum and liver toxicokinetics and the possible formation of BDA-nucleoside adducts in vivo. After gavage exposure, furan concentrations in the liver were consistently higher than those in whole blood (similar to 6-fold), which is consistent with portal vein delivery of a lipophilic compound into the liver. Formation of BDA-2'-deoxycytidine in furan-treated rat liver DNA was not observed using LC/MS/MS after single doses as high as 9.2 mg/kg bw or repeated dosing for up to 360 days above a consistent background level (1-2 adducts per 10(8) nucleotides). This absence of BDA-nucleoside adduct formation is consistent with the general lack of evidence for genotoxicity of furan in vivo. Published by Elsevier Ltd.
C1 [Churchwell, M. I.; Scheri, R. C.; Von Tungeln, L. S.; da Costa, G. Gamboa; Beland, F. A.; Doerge, D. R.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
RP Doerge, DR (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
EM daniel.doerge@fda.hhs.gov
FU FDA; NIEHS/NIH (FDA) [224-12-0003/NIEHS, AES12013]; Oak Ridge Institute
for Science and Education
FX This study was funded by an Interagency Agreement between FDA and
NIEHS/NIH (FDA IAG # 224-12-0003/NIEHS IAG # AES12013). RCS acknowledges
support of a fellowship from the Oak Ridge Institute for Science and
Education, administered through an interagency agreement between the
U.S. Department of Energy and the U.S. Food and Drug Administration. The
authors are grateful for helpful discussions with Drs. Ronald Lorentzen
and Michael Di Novi, U.S. FDA Center for Food Safety and Applied
Nutrition. The views presented in this article do not necessarily
reflect those of the U.S. Food and Drug Administration or National
Toxicology Program.
NR 31
TC 5
Z9 5
U1 3
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-6915
EI 1873-6351
J9 FOOD CHEM TOXICOL
JI Food Chem. Toxicol.
PD DEC
PY 2015
VL 86
BP 1
EP 8
DI 10.1016/j.fct.2015.08.029
PG 8
WC Food Science & Technology; Toxicology
SC Food Science & Technology; Toxicology
GA DB0MW
UT WOS:000368203200001
PM 26364877
ER
PT J
AU Beland, FA
Olson, GR
Mendoza, MCB
Marques, MM
Doerge, DR
AF Beland, Frederick A.
Olson, Greg R.
Mendoza, Maria C. B.
Marques, M. Matilde
Doerge, Daniel R.
TI Carcinogenicity of glycidamide in B6C3F(1) mice and F344/N rats from a
two-year drinking water exposure
SO FOOD AND CHEMICAL TOXICOLOGY
LA English
DT Article
DE Acrylamide; Glycidamide; Tumorigenicity; Mice; Rats; Bioassay
ID DNA ADDUCT FORMATION; TANDEM MASS-SPECTROMETRY; BIG-BLUE MICE;
FISCHER-344 RATS; METABOLITE GLYCIDAMIDE; HEMOGLOBIN ADDUCTS; MAILLARD
REACTION; DOSE-RESPONSE; ACRYLAMIDE; TOXICOKINETICS
AB Acrylamide is a contaminant in baked and fried starchy foods, roasted coffee, and cigarette smoke. Previously we reported that acrylamide is a multi-organ carcinogen in B6C3F(1) mice and F344/N rats, and hypothesized that acrylamide is activated to an ultimate carcinogen through metabolism to the epoxide glycidamide. We have now examined the carcinogenic effects of glycidamide administered at 0, 0.0875, 0.175, 0.35 and 0.70 mM in drinking water to the same strains of rodents for two years. In male and female mice, there were significant increases in tumors of the Harderian gland, lung, forestomach, and skin. Female mice also had an increased incidence of tumors of the mammary gland and ovary. In male and female rats, there were significant increases in thyroid gland and oral cavity neoplasms and mononuclear cell leukemia. Male rats also had increases in tumors of the epididymis/testes and heart, while female rats demonstrated increases in tumors of the mammary gland, clitoral gland, and forestomach. A similar spectrum of tumors was obtained in mice and rats administered acrylamide. These data indicate that, under the conditions of these bioassays, acrylamide is efficiently metabolized to glycidamide and that the carcinogenic activity of acrylamide is due to its conversion into glycidamide. Published by Elsevier Ltd.
C1 [Beland, Frederick A.; Doerge, Daniel R.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
[Olson, Greg R.] Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA.
[Mendoza, Maria C. B.] Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA.
[Marques, M. Matilde] Univ Lisbon, Inst Super Tecn, Ctr Quim Estrutural, P-1049001 Lisbon, Portugal.
RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT 110,3900 NCTR Rd, Jefferson, AR 72079 USA.
EM frederick.beland@fda.hhs.gov
RI Marques, M. Matilde/E-2535-2012; PTMS, RNEM/C-1589-2014
OI Marques, M. Matilde/0000-0002-7526-4962;
FU Interagency Agreement between the National Institute of Environmental
Health Sciences; National Toxicology Program; U.S. Food and Drug
Administration, National Center for Toxicological Research (NCTR/FDA
IAG) [224-12-0003]; U.S. Food and Drug Administration, National Center
for Toxicological Research (NIH/NTP IAG) [AES12013]; Fundacao para a
Ciencia e a Tecnologia, Portugal [RECI/QEQ-MED/0330/2012,
UID/QUI/00100/2013]
FX We thank L. Patrice McDaniel for serving as the study coordinator, and
James Carson, Andy Matson, and Michelle Vanlandingham for providing
animal diets and care. This work was supported by an Interagency
Agreement between the National Institute of Environmental Health
Sciences, National Toxicology Program, and the U.S. Food and Drug
Administration, National Center for Toxicological Research (NCTR/FDA IAG
#224-12-0003; NIH/NTP IAG #AES12013) and formed the basis for NTP
Technical Report 588. Financial support was also provided by a research
grant from Fundacao para a Ciencia e a Tecnologia, Portugal
(RECI/QEQ-MED/0330/2012; UID/QUI/00100/2013). The opinions expressed in
this paper do not necessarily represent those of the U.S. Food and Drug
Administration.
NR 62
TC 0
Z9 0
U1 2
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-6915
EI 1873-6351
J9 FOOD CHEM TOXICOL
JI Food Chem. Toxicol.
PD DEC
PY 2015
VL 86
BP 104
EP 115
DI 10.1016/j.fct.2015.09.017
PG 12
WC Food Science & Technology; Toxicology
SC Food Science & Technology; Toxicology
GA DB0MW
UT WOS:000368203200013
PM 26429628
ER
PT J
AU Neal-Kluever, AP
Bailey, AB
Hatwell, KR
AF Neal-Kluever, April P.
Bailey, Allan B.
Hatwell, Karen R.
TI Safety assessment for octadecyl
3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionate (CAS Reg. No.
2082-79-3) from use in food contact applications
SO FOOD AND CHEMICAL TOXICOLOGY
LA English
DT Article
DE Irganox 1076; Safety assessment; Exposure assessment; Food contact; Food
packaging
ID CERTIFIED REFERENCE MATERIALS; MIGRATION; TEMPERATURE; METABOLISM;
FEASIBILITY; SIMULANTS; MIGRANTS; PLASTICS
AB Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (CAS Reg. No. 2082-79-3), currently marketed as Irganox 1076 (I-76), is a sterically hindered phenolic antioxidant used in a variety of organic substrates, including those used in the manufacture of food contact articles. In 2012, the US Food and Drug Administration (USFDA), Office of Food Additive Safety (OFAS), initiated a post-market re-evaluation of the food contact applications of I-76. This project aimed to ensure that current dietary exposures from the use of I-76 in food contact articles are accurately captured and the safety assessment considered all relevant and available toxicological information. To accomplish these aims, the USFDA reviewed the available toxicological studies and chemistry information on food contact applications of I-76. Based on this in-depth analysis, a NOAEL of 64 mg/kg-bw/d (female rats) from a chronic rat study and a cumulative estimated dietary intake (CEDI) of 4.5 mg/p/d, was used to calculate a margin of exposure (MOE) of similar to 850. We concluded that the previous and current exposure levels provide an adequate margin of safety (MOS) and remain protective of human health for the regulated uses. Published by Elsevier Ltd.
C1 [Neal-Kluever, April P.; Bailey, Allan B.; Hatwell, Karen R.] US FDA, CFSAN, OFAS, College Pk, MD 20740 USA.
RP Neal-Kluever, AP (reprint author), US FDA, CFSAN, OFAS, DFCN, 5100 Paint Branch Pkwy HFS 275, College Pk, MD 20740 USA.
EM april.kluever@fda.hhs.gov
NR 44
TC 0
Z9 0
U1 6
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-6915
EI 1873-6351
J9 FOOD CHEM TOXICOL
JI Food Chem. Toxicol.
PD DEC
PY 2015
VL 86
BP 176
EP 190
DI 10.1016/j.fct.2015.10.004
PG 15
WC Food Science & Technology; Toxicology
SC Food Science & Technology; Toxicology
GA DB0MW
UT WOS:000368203200020
PM 26482640
ER
PT J
AU Park, HJ
Chon, JW
Lim, JS
Seo, KH
Kim, YJ
Heo, EJ
Wee, SH
Sung, K
Moon, JS
AF Park, Hyun-Jung
Chon, Jung-Whan
Lim, Jong-Soo
Seo, Kun-Ho
Kim, Young-Jo
Heo, Eun-Jeong
Wee, Sung-Hwan
Sung, Kidon
Moon, Jin-San
TI Prevalence Analysis and Molecular Characterization of Salmonella at
Different Processing Steps in Broiler Slaughter Plants in South Korea
SO JOURNAL OF FOOD SCIENCE
LA English
DT Article
DE contamination; poultry processing; salmonella; subtyping
ID CAMPYLOBACTER-SPP.; ANTIBIOTIC SUSCEPTIBILITY; ANTIMICROBIAL RESISTANCE;
POULTRY SLAUGHTERHOUSES; MICROBIOLOGICAL QUALITY; CROSS-CONTAMINATION;
CHICKEN CARCASSES; WATER IMMERSION; AIR; OPERATION
AB In this study, changes in the prevalence of Salmonella during the processing of broiler chicken carcasses were investigated. A total of 1040 fecal swabs and chicken carcasses samples were collected from 2 processing plants at the 4 stages of broiler processing, which included live birds in slaughter line, postevisceration/prewashing, postwashing/prechilling, and postchilling, respectively. The intraspecific biodiversity of the Salmonella isolates was determined using a DiversiLab automated repetitive sequence-based PCR (rep-PCR) system. In both plants, the prevalence of Salmonella increased considerably after evisceration (from 4.6% to 30.8%, P < 0.05) and decreased after washing (from 30.8% to 25.4%, P < 0.05). However, the chilling step had little effect on Salmonella prevalence (from 25.4% to 22.7%, P > 0.05). The most frequent Salmonella serovar in plant A was Infantis (35.8%), followed by Enteritidis (26.2%) and Montevideo (15.0%), while Montevideo (43.6%) and Enteritidis (35.9%) were most prevalent in plant B. A difference in the rep-PCR banding pattern was found to be related to the processing plant origin and serovar rather than sampling point or sampling day, although there were some exceptional strains.
C1 [Park, Hyun-Jung; Kim, Young-Jo; Heo, Eun-Jeong] Minist Food & Drug Safety, Cheongju, South Korea.
[Chon, Jung-Whan; Sung, Kidon] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR USA.
[Lim, Jong-Soo; Seo, Kun-Ho] Konkuk Univ, Coll Vet Med, KU Ctr Food Safety, Seoul, South Korea.
[Wee, Sung-Hwan; Moon, Jin-San] Anim & Plant Quarantine Agcy, Anyang, South Korea.
RP Moon, JS (reprint author), Anim & Plant Quarantine Agcy, Anyang, South Korea.
EM moonjs727@korea.kr
FU Animal, Plant and Fisheries Quarantine and Inspection Agency
[B-FS03-2011-12-01]
FX This work was supported by the Animal, Plant and Fisheries Quarantine
and Inspection Agency (No. B-FS03-2011-12-01).
NR 27
TC 2
Z9 2
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-1147
EI 1750-3841
J9 J FOOD SCI
JI J. Food Sci.
PD DEC
PY 2015
VL 80
IS 12
BP M2822
EP M2826
DI 10.1111/1750-3841.13106
PG 5
WC Food Science & Technology
SC Food Science & Technology
GA DA9MI
UT WOS:000368132800023
PM 26523619
ER
PT J
AU Li, G
Schoneker, D
Ulman, KL
Sturm, JJ
Thackery, LM
Kauffman, JF
AF Li, Gang
Schoneker, Dave
Ulman, Katherine L.
Sturm, Jason J.
Thackery, Lisa M.
Kauffman, John F.
TI Elemental Impurities in Pharmaceutical Excipients
SO JOURNAL OF PHARMACEUTICAL SCIENCES
LA English
DT Article
DE trace elements; US FDA; trace metal; excipients; microwave-assisted
digestion; ICP-MS; Analytical Chemistry; Global Health; Mass
Spectrometry; Regulatory Science
AB Control of elemental impurities in pharmaceutical materials is currently undergoing a transition from control based on concentrations in components of drug products to control based on permitted daily exposures in drug products. Within the pharmaceutical community, there is uncertainty regarding the impact of these changes on manufactures of drug products. This uncertainty is fueled in part by a lack of publically available information on elemental impurity levels in common pharmaceutical excipients. This paper summarizes a recent survey of elemental impurity levels in common pharmaceutical excipients as well as some drug substances. A widely applicable analytical procedure was developed and was shown to be suitable for analysis of elements that are subject to United States Pharmacopoeia Chapter <232> and International Conference on Harmonization's Q3D Guideline on Elemental Impurities. The procedure utilizes microwave-assisted digestion of pharmaceutical materials and inductively coupled plasma mass spectrometry for quantitative analysis of these elements. The procedure was applied to 190 samples from 31 different excipients and 15 samples from eight drug substances provided through the International Pharmaceutical Excipient Council of the Americas. The results of the survey indicate that, for the materials included in the study, relatively low levels of elemental impurities are present. (C) 2015 Wiley Periodicals, Inc. and the American Pharmacists Association
C1 [Li, Gang; Kauffman, John F.] US FDA, Div Pharmaceut Anal, St Louis, MO 63110 USA.
[Schoneker, Dave] Colorcon Inc, Harleysville, PA 19438 USA.
[Ulman, Katherine L.] Dow Corning Healthcare Business, Midland, MI 48686 USA.
[Sturm, Jason J.; Thackery, Lisa M.] Dow Corning Analyt Sci, Midland, MI 48686 USA.
[Schoneker, Dave; Ulman, Katherine L.] IPEC Amer, Arlington, VA 22201 USA.
RP Kauffman, JF (reprint author), US FDA, Div Pharmaceut Anal, St Louis, MO 63110 USA.
EM John.Kauffman@fda.hhs.gov
NR 10
TC 3
Z9 3
U1 5
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3549
EI 1520-6017
J9 J PHARM SCI-US
JI J. Pharm. Sci.
PD DEC
PY 2015
VL 104
IS 12
BP 4197
EP 4206
DI 10.1002/jps.24650
PG 10
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology &
Pharmacy
SC Pharmacology & Pharmacy; Chemistry
GA DA9PG
UT WOS:000368141200023
PM 26398581
ER
PT J
AU Nguyenpho, A
Ciavarella, AB
Siddiqui, A
Rahman, Z
Akhtar, S
Hunt, R
Korang-Yeboah, M
Khan, MA
AF Nguyenpho, Agnes
Ciavarella, Anthony B.
Siddiqui, Akhtar
Rahman, Ziyaur
Akhtar, Sohail
Hunt, Robert
Korang-Yeboah, Maxwell
Khan, Mansoor A.
TI Evaluation of In-Use Stability of Anticoagulant Drug Products: Warfarin
Sodium
SO JOURNAL OF PHARMACEUTICAL SCIENCES
LA English
DT Article
DE amorphous; clathrates; crystallinity; dissolution; near-infrared
spectroscopy; stability; X-ray powder diffractometry
ID CRYSTALLINITY; MOISTURE
AB The objective of the study was to evaluate the stability of warfarin products during use by patients or caregivers. For evaluation, three commercial products manufactured by different processes were selected and placed at 30 degrees C/75%RH to simulate in use condition. Samples were withdrawn up to 12 weeks and analyzed for the physicochemical changes. Scanning electron microscopy demonstrated increasing holes and craters in the tablets over the timeframe. Near-infrared chemical imaging and powder X-ray powder diffraction corroborated the change arising from conversion of crystalline to amorphous forms of the drug. Hardness and disintegration time of the tablets were found to increase progressively. With increasing time, moisture contents of the products were found to increase and consequent decrease in isopropyl alcohol content of the product. Dissolution of the tablets in media at pH 4.5 demonstrated discrimination between crystalline and amorphous drug products. Overall, percent drug dissolved in each product at 30 min was found to decrease with increasing exposure time. Dissolution of drug decreased from 54% to 38% and 82% to 54% for the two products while the third product maintained consistently high level of dissolution. These results suggest that the drug product quality attributes can change during use. (C) 2015 Wiley Periodicals, Inc. and the American Pharmacists Association
C1 [Nguyenpho, Agnes; Ciavarella, Anthony B.; Siddiqui, Akhtar; Rahman, Ziyaur; Akhtar, Sohail; Hunt, Robert; Korang-Yeboah, Maxwell; Khan, Mansoor A.] US FDA, Div Prod Qual Res, Ctr Drug Evaluat Res, Silver Spring, MD 20993 USA.
RP Khan, MA (reprint author), Texas A&M Hlth Sci Ctr, Rangel Coll Pharm, College Stn, TX 77843 USA.
EM mkhan@pharmacy.tamhsc.edu
OI Rahman, Ziyaur/0000-0002-0402-825X
NR 16
TC 1
Z9 1
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3549
EI 1520-6017
J9 J PHARM SCI-US
JI J. Pharm. Sci.
PD DEC
PY 2015
VL 104
IS 12
BP 4232
EP 4240
DI 10.1002/jps.24657
PG 9
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology &
Pharmacy
SC Pharmacology & Pharmacy; Chemistry
GA DA9PG
UT WOS:000368141200027
PM 26501849
ER
PT J
AU Boudewyns, V
O'Donoghue, AC
Kelly, B
West, SL
Oguntimein, O
Bann, CM
McCormack, LA
AF Boudewyns, Vanessa
O'Donoghue, Amie C.
Kelly, Bridget
West, Suzanne L.
Oguntimein, Oluwamurewa
Bann, Carla M.
McCormack, Lauren A.
TI Influence of patient medication information format on comprehension and
application of medication information: A randomized, controlled
experiment
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Article
ID HEALTH LITERACY; PHARMACIES; INSTRUMENT; MEDICINES; LEAFLETS; GUIDES
AB Objective: To examine patients' comprehension and application of alternative versions of patient medication information handouts for a fictitious drug, and whether patient characteristics influence patients' ability to understand the handouts.
Methods: A web-based experiment was conducted in which 1397 adults with rheumatoid arthritis, ankylosing spondylitis, or plaque psoriasis were randomly assigned to one of three conditions: (1) a one-page "Bubbles" format; (2) a one-page "Over-The-Counter" (OTC) format; and (3) a four-page document modeled after MedGuides used in 2009 which served as the control arm. Comprehension and application of information in the handouts were the key outcomes of interest.
Results: Participants who viewed either the Bubbles or OTC formats had greater comprehension than participants who viewed the MedGuide, but did not have better application scores. No significant differences were noted between the Bubbles and OTC formats. Patient characteristics did not moderate the results.
Conclusion: Both formats resulted in better comprehension than the MedGuide format used in the study.
Practice implications: Results provide valuable information on how to design patient information to improve patients' understanding of the risks and benefits of the drugs they are prescribed. Results could be extended to inform the content of other types of patient education materials. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Boudewyns, Vanessa; Kelly, Bridget; West, Suzanne L.; Bann, Carla M.; McCormack, Lauren A.] RTI Int, Res Triangle Pk, NC USA.
[O'Donoghue, Amie C.; Oguntimein, Oluwamurewa] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Boudewyns, V (reprint author), 701 13th St NW,Ste 750, Washington, DC 20005 USA.
EM vboudewyns@rti.org
FU Center for Drug Evaluation and Research, FDA
FX The Center for Drug Evaluation and Research, FDA, provided research
funding for this study. Two authors are employed by the funding source,
and the others received contracted funding through this source.
NR 43
TC 3
Z9 3
U1 0
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0738-3991
J9 PATIENT EDUC COUNS
JI Patient Educ. Couns.
PD DEC
PY 2015
VL 98
IS 12
BP 1592
EP 1599
DI 10.1016/j.pec.2015.07.003
PG 8
WC Public, Environmental & Occupational Health; Social Sciences,
Interdisciplinary
SC Public, Environmental & Occupational Health; Social Sciences - Other
Topics
GA DB2IV
UT WOS:000368332400015
ER
PT J
AU Custer, B
Sheon, N
Siedle-Khan, B
Pollack, L
Spencer, B
Bialkowski, W
D'Andrea, P
Sullivan, M
Glynn, S
Williams, A
AF Custer, Brian
Sheon, Nicolas
Siedle-Khan, Bob
Pollack, Lance
Spencer, Bryan
Bialkowski, Walter
D'Andrea, Pam
Sullivan, Marian
Glynn, Simone
Williams, Alan
CA NHLBI Recipient Epidemiology Donor
TI Blood donor deferral for men who have sex with men: the Blood Donation
Rules Opinion Study (Blood DROPS)
SO TRANSFUSION
LA English
DT Article
ID TRANSFUSION-TRANSMITTED HIV; EVER HAD SEX; GAY MEN; RISK; POLICY;
IMPACT; DISCRIMINATION; EXCLUSION; ENGLAND; WALES
AB BACKGROUND: In the United States, any man who discloses having had sex with another man (MSM) even once since 1977 is currently deferred from donating blood. A study was conducted to assess noncompliance with the policy at four geographically dispersed blood centers.
STUDY DESIGN AND METHODS: Male donors 18+ years of age with e-mail addresses were randomly selected and invited to complete a confidential online survey between August and October 2013. No additional recruitment e-mails were sent. Survey content included demographics, sexual history, donation history, compliance with the policy, and opinions about current and modified policies.
RESULTS: Response rate was 11.5% but varied by center (6.3% to 21.7%). Of 3183 completed surveys, 2.6% of respondents (95% confidence interval, 2.1%-3.2%) reported donation after male-male sex. Noncompliance was not statistically different among the centers (p=0.1), but was related to age with 5.7, 4.6, 2.5, and 1.0% of donors 18 to 24, 25 to 34, 35 to 54, and 50+ years of age, respectively, reporting noncompliance (p<0.001). Of all respondents, 6.8% reported at least six female and 0.3% reported at least six male sex partners in the past 5 years. Opinions about the current MSM policy were mixed with noncomplying donors more supportive of change than complying donors. Approximatey half of noncompliers indicated they would adhere to a 1-year deferral.
CONCLUSION: Noncompliance with the MSM policy is evident and may be increasing compared to earlier data. Any change from the current policy will require close monitoring to determine whether it affects residual risk of HIV in the US blood supply.
C1 [Custer, Brian] UCSF, Blood Syst Res Inst, San Francisco, CA USA.
[Custer, Brian] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
[Sheon, Nicolas; Siedle-Khan, Bob; Pollack, Lance] UCSF, Ctr AIDS Prevent Studies, San Francisco, CA USA.
[Spencer, Bryan] Amer Red Cross, Dedham, MA USA.
[Bialkowski, Walter] BloodCtr Wisconsin, Milwaukee, WI USA.
[D'Andrea, Pam] Inst Transfus Med, Pittsburgh, PA USA.
[Sullivan, Marian] RTI Int, Rockville, MD USA.
[Glynn, Simone] NHLBI, Bethesda, MD 20892 USA.
[Williams, Alan] US FDA, Silver Spring, MD USA.
RP Custer, B (reprint author), Blood Syst Res Inst, 270 Mason Ave, San Francisco, CA 94118 USA.
EM bcuster@bloodsystems.org
FU US FDA; NHLBI REDS-III program
FX This study was funded by the US FDA and the NHLBI REDS-III program.
NR 34
TC 9
Z9 9
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD DEC
PY 2015
VL 55
IS 12
BP 2826
EP 2834
DI 10.1111/trf.13247
PG 9
WC Hematology
SC Hematology
GA DA6YB
UT WOS:000367950600010
PM 26202349
ER
PT J
AU Rahman, Z
Mohammad, A
Siddiqui, A
Khan, MA
AF Rahman, Ziyaur
Mohammad, Adil
Siddiqui, Akhtar
Khan, Mansoor A.
TI Comparison of Univariate and Multivariate Models of C-13 SSNMR and XRPD
Techniques for Quantification of Nimodipine Polymorphs
SO AAPS PHARMSCITECH
LA English
DT Article
DE nimodipine polymorphs; X-ray powder diffraction; solid-state nuclear
magnetic resonance; univariate; multivariate
ID SOLID-STATE CHARACTERIZATION; RAMAN-SPECTROSCOPY; NMR-SPECTROSCOPY;
CPMAS NMR; DISPERSIONS; MIXTURES; BINARY
AB The focus of the present investigation was to explore the use of solid-state nuclear magnetic resonance (C-13 ssNMR) and X-ray powder diffraction (XRPD) for quantification of nimodipine polymorphs (form I and form II) crystallized in a cosolvent formulation. The cosolvent formulation composed of polyethylene glycol 400, glycerin, water, and 2.5% drug, and was stored at 5 degrees C for the drug crystallization. The C-13 ssNMR and XRPD data of the sample matrices containing varying percentages of nimodipine form I and form II were collected. Univariate and multivariate models were developed using the data. Least square method was used for the univariate model generation. Partial least square and principle component regressions were used for the multivariate models development. The univariate models of the C-13 ssNMR were better than the XRPD as indicated by statistical parameters such as correlation coefficient, R-2, root mean square error, and standard error. On the other hand, the XRPD multivariate models were better than the C-13 ssNMR as indicated by precision and accuracy parameters. Similar values were predicted by the univariate and multivariate models for independent samples. In conclusion, the univariate and multivariate models of C-13 ssNMR and XRPD can be used to quantitate nimodipine polymorphs.
C1 [Rahman, Ziyaur; Mohammad, Adil; Siddiqui, Akhtar; Khan, Mansoor A.] US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, Div Prod Qual Res, Silver Spring, MD 20993 USA.
RP Khan, MA (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, Div Prod Qual Res, LS Bldg 64,Room 1070,10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM Mansoor.Khan@fda.hhs.gov
OI Rahman, Ziyaur/0000-0002-0402-825X
NR 22
TC 0
Z9 0
U1 1
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1530-9932
J9 AAPS PHARMSCITECH
JI AAPS PharmSciTech
PD DEC
PY 2015
VL 16
IS 6
BP 1368
EP 1376
DI 10.1208/s12249-015-0327-8
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DA0YS
UT WOS:000367524100015
PM 25956485
ER
PT J
AU Selker, HP
Buse, JB
Califf, RM
Carter, R
Cooper, DM
Davis, J
Ford, DE
Galassetti, P
Guay-Woodford, L
Huggins, GS
Kasper, A
Kieburtz, K
Kirby, A
Klein, AK
Kline, J
Neill, RT
Rape, M
Reichgott, DJ
Rojevsky, S
Rosenthal, GE
Rubinstein, EP
Shepherd, A
Stacy, M
Terrin, N
Wallace, M
Welch, L
AF Selker, Harry P.
Buse, John B.
Califf, Robert M.
Carter, Robert
Cooper, Dan M.
Davis, Jonathan
Ford, Daniel E.
Galassetti, Pietro
Guay-Woodford, Lisa
Huggins, Gordon S.
Kasper, Amanda
Kieburtz, Karl
Kirby, Aaron
Klein, Andreas K.
Kline, Joel
O' Neill, Robert T.
Rape, Marie
Reichgott, Douglas J.
Rojevsky, Svetlana
Rosenthal, Gary E.
Rubinstein, Eric P.
Shepherd, Amy
Stacy, Mark
Terrin, Norma
Wallace, Mark
Welch, Lisa
TI CTSA Consortium Consensus Scientific Review Committee (SRC) Working
Group Report on the SRC Processes
SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE
LA English
DT Article
DE translational research; clinical trials; outcomes research
AB Human research projects must have a scientifically valid study design, analytic plan, and be operationally feasible in order to be successfully completed and thus to have translational impact. To ensure this, institutions that conduct clinical research should have a scientific review process prior to submission to the Institutional Review Committee (IRB). This paper reports the Clinical and Translational Science Award (CTSA) Consortium Scientific Review Committee (SRC) Consensus Working Group's proposed framework for a SRC process. Recommendations are provided for institutional support and roles of CTSAs, multisite research, criteria for selection of protocols that should be reviewed, roles of committee members, application process, and committee process. Additionally, to support the SCR process effectively, and to ensure efficiency, the Working Group recommends information technology infrastructures and evaluation metrics to determine outcomes are provided.
C1 [Selker, Harry P.; Davis, Jonathan; Kirby, Aaron; Rojevsky, Svetlana; Shepherd, Amy; Terrin, Norma; Welch, Lisa] Tufts Med Ctr, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA.
[Buse, John B.; Rape, Marie] Univ N Carolina, Translat & Clin Sci Inst, Chapel Hill, NC USA.
[Califf, Robert M.; Stacy, Mark] Duke Univ, Duke Translat Med Inst, Durham, NC USA.
[Carter, Robert] NIH, Bethesda, MD 20892 USA.
[Cooper, Dan M.; Galassetti, Pietro] Univ Calif Irvine, Inst Clin & Translat Sci, Irvine, CA USA.
[Ford, Daniel E.] Johns Hopkins Univ, Inst Clin & Translat Res, Baltimore, MD USA.
[Guay-Woodford, Lisa; Kasper, Amanda] Clin & Translat Sci Inst Childrens Natl, Washington, DC USA.
[Huggins, Gordon S.; Klein, Andreas K.; Reichgott, Douglas J.] Tufts Med Ctr, Boston, MA USA.
[Kieburtz, Karl; Rubinstein, Eric P.] Univ Rochester, Med Ctr, Clin & Translat Sci Inst, Rochester, NY 14642 USA.
[Kline, Joel; Rosenthal, Gary E.] Univ Iowa, Inst Clin & Translat Sci, Iowa City, IA USA.
[O' Neill, Robert T.] US FDA, Silver Spring, MD USA.
[Wallace, Mark] Univ Calif San Diego, Clin & Translat Res Inst, San Diego, CA 92103 USA.
RP Selker, HP (reprint author), Tufts Med Ctr, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA.
EM HSelker@tuftsmedicalcenter.org
FU National Institutes of Health Clinical and Translational Science Awards
[UL1 TR001064]; University of North Carolina at Chapel Hill,
Translational & Clinical Sciences Institute [1UL1TR001111]; Duke
Translational Medicine Institute, Duke University, Institute for
Clinical and Translational Science [UL1TR001117]; University of
California, Irvine, Institute for Clinical and Translational Research
[UL1TR000153]; Johns Hopkins University, Institute for Clinical &
Translational Research [UL1TR001079]; Clinical and Translational Science
Institute at Children's National Center for Translational Science
[UL1TR000075]; University of Rochester Clinical and Translational
Science Institute [UL1TR000042]; Institute for Clinical and
Translational Science at the University of Iowa [U54TR001013]; Clinical
and Translational Research Institute, University of California, San
Diego [UL1TR000100]
FX This paper was supported by an administrative supplement award to the
Tufts CTSI from the National Institutes of Health Clinical and
Translational Science Awards (UL1 TR001064), with additional support
from the Working Group's affiliated CTSAs. The affiliated CTSAs include:
University of North Carolina at Chapel Hill, Translational & Clinical
Sciences Institute (1UL1TR001111), Duke Translational Medicine
Institute, Duke University, Institute for Clinical and Translational
Science (UL1TR001117), University of California, Irvine, Institute for
Clinical and Translational Research (UL1TR000153), Johns Hopkins
University, Institute for Clinical & Translational Research
(UL1TR001079), The Clinical and Translational Science Institute at
Children's National Center for Translational Science (UL1TR000075),
University of Rochester Clinical and Translational Science Institute
(UL1TR000042), Institute for Clinical and Translational Science at the
University of Iowa (U54TR001013), and Clinical and Translational
Research Institute, University of California, San Diego (UL1TR000100).
NR 0
TC 0
Z9 0
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1752-8054
EI 1752-8062
J9 CTS-CLIN TRANSL SCI
JI CTS-Clin. Transl. Sci.
PD DEC
PY 2015
VL 8
IS 6
BP 623
EP 631
DI 10.1111/cts.12306
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DA3DL
UT WOS:000367676600007
PM 26184433
ER
PT J
AU Li, LL
Kulldorff, M
Russek-Cohen, E
Kawai, AT
Hua, W
AF Li, Lingling
Kulldorff, Martin
Russek-Cohen, Estelle
Kawai, Alison Tse
Hua, Wei
TI Quantifying the impact of time-varying baseline risk adjustment in the
self-controlled risk interval design
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Article
DE self-controlled risk interval; time-varying risks; self-controlled case
series; vaccine safety; drug safety; adverse reaction;
pharmacoepidemiology
ID SAFETY DATALINK PROJECT; INACTIVATED INFLUENZA VACCINE; ROTAVIRUS
VACCINATION; US INFANTS; CHILDREN; SURVEILLANCE; PROGRAM; H1N1
AB Purpose The self-controlled risk interval design is commonly used to assess the association between an acute exposure and an adverse event of interest, implicitly adjusting for fixed, non-time-varying covariates. Explicit adjustment needs to be made for time-varying covariates, for example, age in young children. It can be performed via either a fixed or random adjustment. The random-adjustment approach can provide valid point and interval estimates but requires access to individual-level data for an unexposed baseline sample. The fixed-adjustment approach does not have this requirement and will provide a valid point estimate but may underestimate the variance. We conducted a comprehensive simulation study to evaluate their performance.
Methods We designed the simulation study using empirical data from the Food and Drug Administration-sponsored Mini-Sentinel Post-licensure Rapid Immunization Safety Monitoring Rotavirus Vaccines and Intussusception study in children 5-36.9 weeks of age. The time-varying confounder is age. We considered a variety of design parameters including sample size, relative risk, time-varying baseline risks, and risk interval length.
Results The random-adjustment approach has very good performance in almost all considered settings. The fixed-adjustment approach can be used as a good alternative when the number of events used to estimate the time-varying baseline risks is at least the number of events used to estimate the relative risk, which is almost always the case.
Conclusions We successfully identified settings in which the fixed-adjustment approach can be used as a good alternative and provided guidelines on the selection and implementation of appropriate analyses for the self-controlled risk interval design. Copyright (C) 2015 John Wiley & Sons, Ltd.
C1 [Li, Lingling; Kulldorff, Martin; Kawai, Alison Tse] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA 02214 USA.
[Li, Lingling; Kulldorff, Martin; Kawai, Alison Tse] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Russek-Cohen, Estelle; Hua, Wei] US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Silver Spring, MD USA.
RP Li, LL (reprint author), Harvard Pilgrim Hlth Care Inst, Dept Populat Med, 133 Brookline Ave,6th Floor, Boston, MA 02214 USA.
EM lingling_li@post.harvard.edu
FU Department of Health and Human Services; Food and Drug Administration;
Mini-Sentinel; PRISM programs [HHSF223200910006I]
FX Supported by funding from the Food and Drug Administration, through the
Department of Health and Human Services, for the Mini-Sentinel and PRISM
programs (contract number HHSF223200910006I).
NR 22
TC 0
Z9 1
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-8569
EI 1099-1557
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD DEC
PY 2015
VL 24
IS 12
BP 1304
EP 1312
DI 10.1002/pds.3885
PG 9
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA DA3CI
UT WOS:000367673100009
PM 26464236
ER
PT J
AU Heindel, JJ
Newbold, RR
Bucher, JR
Camacho, L
Delclos, KB
Lewis, SM
Vanlandingham, M
Churchwell, MI
Twaddle, NC
McLellen, M
Chidambaram, M
Bryant, M
Woodling, K
da Costa, GG
Ferguson, SA
Flaws, J
Howard, PC
Walker, NJ
Zoeller, RT
Fostel, J
Favaro, C
Schug, TT
AF Heindel, Jerrold J.
Newbold, Retha R.
Bucher, John R.
Camacho, Luisa
Delclos, K. Barry
Lewis, Sherry M.
Vanlandingham, Michelle
Churchwell, Mona I.
Twaddle, Nathan C.
McLellen, Michelle
Chidambaram, Mani
Bryant, Matthew
Woodling, Kellie
da Costa, Goncalo Gamboa
Ferguson, Sherry A.
Flaws, Jodi
Howard, Paul C.
Walker, Nigel J.
Zoeller, R. Thomas
Fostel, Jennifer
Favaro, Carolyn
Schug, Thaddeus T.
TI NIEHS/FDA CLARITY-BPA research program update
SO REPRODUCTIVE TOXICOLOGY
LA English
DT Review
DE Bisphenol A; NIEHS; FDA; NTP; CLARITY-BPA; Consortium; Endocrine
disruptors
ID SPRAGUE-DAWLEY RATS; ESTROGEN-RECEPTOR EXPRESSION; BISPHENOL-A; ETHINYL
ESTRADIOL; THYROID-HORMONES; DNA METHYLATION; ORAL-EXPOSURE; CELL
BIOLOGY; FEMALE; TOXICITY
AB Bisphenol A (BPA) is a chemical used in the production of numerous consumer products resulting in potential daily human exposure to this chemical. The FDA previously evaluated the body of BPA toxicology data and determined that BPA is safe at current exposure levels. Although consistent with the assessment of some other regulatory agencies around the world, this determination of BPA safety continues to be debated in scientific and popular publications, resulting in conflicting messages to the public. Thus, the National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), and U.S. Food and Drug Administration (FDA) developed a consortium-based research program to link more effectively a variety of hypothesis-based research investigations and guideline-compliant safety testing with BPA. This collaboration is known as the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). This paper provides a detailed description of the conduct of the study and a midterm update on progress of the CLARITY-BPA research program. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
C1 [Heindel, Jerrold J.; Schug, Thaddeus T.] NIEHS, NIH, Div Extramural Res & Training, Res Triangle Pk, NC 27709 USA.
[Newbold, Retha R.; Bucher, John R.; Walker, Nigel J.; Fostel, Jennifer] NIEHS, NIH, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Camacho, Luisa; Delclos, K. Barry; Vanlandingham, Michelle; Churchwell, Mona I.; Twaddle, Nathan C.; McLellen, Michelle; Chidambaram, Mani; Bryant, Matthew; Woodling, Kellie; da Costa, Goncalo Gamboa] USDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Ferguson, Sherry A.] USDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Flaws, Jodi] Univ Illinois, Dept Comparat Biosci, Urbana, IL 61802 USA.
[Lewis, Sherry M.; Howard, Paul C.] USDA, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Zoeller, R. Thomas] Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA.
[Favaro, Carolyn] NIEHS, Team Vistronix, NTP Comp & User Support, NIH,Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Heindel, JJ (reprint author), NIEHS, NIH, Div Extramural Res & Training, POB 12233, Res Triangle Pk, NC 27709 USA.
EM heindelj@niehs.nih.gov
RI Walker, Nigel/D-6583-2012
OI Walker, Nigel/0000-0002-9111-6855
FU National Toxicology Program; Food and Drug Administration; National
Institute of Environmental Health Sciences/National Institutes of Health
[FDA IAG: 224-12-0003, NIEHS IAG: AES12013]
FX The NCTR portion of the study was conducted under the auspices of the
National Toxicology Program and funded by an Interagency agreement (JAG)
between the Food and Drug Administration and the National Institute of
Environmental Health Sciences/National Institutes of Health (FDA IAG:
224-12-0003; NIEHS IAG: AES12013). We are grateful for the extraordinary
efforts of the NCTR Animal Care, Diet Preparation, Information
Technology, Microbiology, Pathology, Quality Assurance, and Veterinary
Services staffs, the NIP Statistical Support Team of the Division of
Bioinformatics and Biostatistics, as well as Ms. Kathy Carroll of the
Office of Scientific Coordination, in the planning and conduct of this
study. This manuscript was reviewed in accordance with USFDA and NIEHS
procedures prior to submission. The opinions expressed in this paper do
not necessarily reflect those of the USFDA.
NR 34
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Z9 7
U1 8
U2 23
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0890-6238
J9 REPROD TOXICOL
JI Reprod. Toxicol.
PD DEC
PY 2015
VL 58
BP 33
EP 44
DI 10.1016/j.reprotox.2015.07.075
PG 12
WC Reproductive Biology; Toxicology
SC Reproductive Biology; Toxicology
GA DA1MJ
UT WOS:000367559600005
PM 26232693
ER
PT J
AU Dreher-Lesnick, SM
Schreier, JE
Stibitz, S
AF Dreher-Lesnick, Sheila M.
Schreier, Jeremy E.
Stibitz, Scott
TI Development of Phage Lysin LysA2 for Use in Improved Purity Assays for
Live Biotherapeutic Products
SO VIRUSES-BASEL
LA English
DT Article
DE endolysin; live biotherapeutic product; probiotics; purity assay; phage
lysins; LysA2; Lactobacillus
ID WALL BINDING DOMAINS; STAPHYLOCOCCUS-AUREUS; BACTERIOPHAGE ENDOLYSINS;
STREPTOCOCCUS-PNEUMONIAE; LYTIC ACTIVITY; ANTIMICROBIALS;
ANTIBACTERIALS; ENZYME; MILK; MICE
AB Live biotherapeutic products (LBPs), commonly referred to as probiotics, are typically preparations of live bacteria, such as Lactobacillus and Bifidobacterium species that are considered normal human commensals. Popular interest in probiotics has been increasing with general health benefits being attributed to their consumption, but there is also growing interest in evaluating such products for treatment of specific diseases. While over-the-counter probiotics are generally viewed as very safe, at least in healthy individuals, it must be remembered that clinical studies to assess these products may be done in individuals whose defenses are compromised, such as through a disease process, immunosuppressive clinical treatment, or an immature or aging immune system. One of the major safety criteria for LBPs used in clinical studies is microbial purity, i.e., the absence of extraneous, undesirable microorganisms. The main goal of this project is to develop recombinant phage lysins as reagents for improved purity assays for LBPs. Phage lysins are hydrolytic enzymes containing a cell binding domain that provides specificity and a catalytic domain responsible for lysis and killing. Our approach is to use recombinant phage lysins to selectively kill target product bacteria, which when used for purity assays will allow for outgrowth of potential contaminants under non-selective conditions, thus allowing an unbiased assessment of the presence of contaminants. To develop our approach, we used LysA2, a phage lysin with reported activity against a broad range of Lactobacillus species. We report the lytic profile of a non-tagged recombinant LysA2 against Lactobacillus strains in our collection. We also present a proof-of-concept experiment, showing that addition of partially purified LysA2 to a culture of Lactobacillus jensenii (L. jensenii) spiked with low numbers of Escherichia coli (E. coli) or Staphylococcus aureus (S. aureus ) effectively eliminates or knocks down L. jensenii, allowing for clear detection of the contaminating strains. With continued identification and characterization of phage lysins, we hope that the use of recombinant phage lysins in purity assays for products containing live microbials may offer additional tools to help advance product development of LBPs.
C1 [Dreher-Lesnick, Sheila M.; Schreier, Jeremy E.; Stibitz, Scott] US FDA, Off Vaccines Res & Review, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
RP Dreher-Lesnick, SM (reprint author), US FDA, Off Vaccines Res & Review, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
EM Sheila.Dreher-Lesnick@fda.hhs.gov; Jeremy.Schreier@fda.hhs.gov;
Earle.Stibitz@fda.hhs.gov
FU FDA [AI-12029-001]
FX We would like to thank Debbie Hinton for the pNW129 expression vector.
We would also like to thank Allison O'Brien and Mark Shirtliff for the
E. coli and S. aureus strains used in this study. Acknowledgements also
go to Amanda Ngouajio and Margaret Libonati, who helped with protocol
development. This work was funded by FDA targeted funding under the
Critical Path Initiative and an Interagency agreement between FDA/CBER
and NIH/NIAID (AI-12029-001). This work was also made possible by the
ORAU/ORISE program.
NR 24
TC 0
Z9 0
U1 3
U2 6
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD DEC
PY 2015
VL 7
IS 12
BP 6675
EP 6688
DI 10.3390/v7122965
PG 14
WC Virology
SC Virology
GA DA1DO
UT WOS:000367536700039
PM 26694451
ER
PT J
AU Hayford, AE
Brown, EW
Zhao, SH
Mammel, MK
Gangiredla, J
Abbott, JW
Friedman, SL
Ayers, SL
Lewis, JL
Lacher, DW
McDermott, P
Elkins, CA
AF Hayford, Alice E.
Brown, Eric W.
Zhao, Shaohua
Mammel, Mark K.
Gangiredla, Jayanthi
Abbott, Jason W.
Friedman, Sharon L.
Ayers, Sherry L.
Lewis, Jada L.
Lacher, David W.
McDermott, Patrick
Elkins, Christopher A.
TI Genetic and resistance phenotypic subtyping of Salmonella Saintpaul
isolates from various food sources and humans: Phylogenetic concordance
in combinatory analyses
SO INFECTION GENETICS AND EVOLUTION
LA English
DT Article
DE Salmonella Saintpaul; Single nucleotide polymorphism; PFGE; Antibiotic
resistance; Phylogenetics
ID ENTERICA SEROVAR SAINTPAUL; FIELD GEL-ELECTROPHORESIS; SEROTYPE
SAINTPAUL; UNITED-STATES; REFERENCE COLLECTION; MULTISTATE OUTBREAK;
SEQUENCE ALIGNMENT; INFECTIONS; TYPHIMURIUM; STRAINS
AB Bacterial pathogen subtyping for public health traceback of foodborne outbreaks has increasingly produced a number of disparate molecular techniques of varying resolution. Here, we bridge the molecular divide across three methodologies, transform data types for cross-comparison, and test phylogenetic concordance. Single nucleotide polymorphism(SNP) discovery was combined with pulsed-field gel electrophoresis (PFGE) and antimicrobial susceptibility profiles for identifying and differentiating 183 strains of closely related Salmonella enterica serovar Saintpaul isolates from retail meats, produce-associated outbreaks, and clinical sources. Fifty-six SNPs across 30 different genes were identified by comparative genomic analysis. These SNPs stratified general, monophyletic S. Saintpaul serovar specific signatures down to informative strain-specific markers. This SNP panel resulted in 17 distinct genotypes that, in concert with standard PFGE profiling, generated additional discriminatory power among clonal swarms of isolates when the data were transformed into a cross-comparable binary format. In a limited number of cases, antimicrobial susceptibility profiles (ASP) provided additional attributes for some strains when combined similarly. However, as expected from presumably acquired elements, resistant and susceptible populations produced some conflicting signals in most clonal complexes but they remained largely undisruptive to the general concordance. Taken in concert together, the three datasets (SNPs, PFGE, ASP) yielded a matrix of 156 independent phylogenetic characters that were statistically evaluated and found to be largely congruent, resulting in a consistently structured, non-homoplastic, phylogenetic signal and tree topology. Published by Elsevier B.V.
C1 [Hayford, Alice E.; Mammel, Mark K.; Gangiredla, Jayanthi; Lewis, Jada L.; Lacher, David W.; Elkins, Christopher A.] US FDA, Div Mol Biol, Ctr Food Safety Appl Nutr, Laurel, MD 20708 USA.
[Brown, Eric W.] US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Zhao, Shaohua; Abbott, Jason W.; Friedman, Sharon L.; Ayers, Sherry L.] US FDA, Div Anim & Food Microbiol, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA.
[McDermott, Patrick] US FDA, Natl Antimicrobial Resistance Monitoring Syst, Ctr Vet Med, Laurel, MD 20708 USA.
RP Hayford, AE (reprint author), US FDA, Div Mol Biol, Ctr Food Safety Appl Nutr, Laurel, MD 20708 USA.
EM alice.hayford@fda.hhs.gov
NR 61
TC 0
Z9 0
U1 3
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1567-1348
EI 1567-7257
J9 INFECT GENET EVOL
JI Infect. Genet. Evol.
PD DEC
PY 2015
VL 36
BP 92
EP 107
DI 10.1016/j.meegid.2015.08.022
PG 16
WC Infectious Diseases
SC Infectious Diseases
GA DA1IA
UT WOS:000367548300013
PM 26299886
ER
PT J
AU Jang, S
Yu, LR
Abdelmegeed, MA
Gao, Y
Banerjee, A
Song, BJ
AF Jang, Sehwan
Yu, Li-Rong
Abdelmegeed, Mohamed A.
Gao, Yuan
Banerjee, Atrayee
Song, Byoung-Joon
TI Critical role of c-jun N-terminal protein kinase in promoting
mitochondrial dysfunction and acute liver injury
SO REDOX BIOLOGY
LA English
DT Article
DE Acute liver injury; Carbon tetrachloride; JNK; Protein phosphorylation;
Mitochondria; Differential proteomics
ID CARBON-TETRACHLORIDE; RAT-LIVER; JNK INHIBITOR; ACETAMINOPHEN
HEPATOTOXICITY; APOPTOSIS; TOXICITY; TRANSLOCATION; ACTIVATION; ALCOHOL;
DAMAGE
AB The mechanism by which c-Jun N-terminal protein kinase (JNK) promotes tissue injury is poorly understood. Thus we aimed at studying the roles of JNK and its phospho-target proteins in mouse models of acute liver injury. Young male mice were exposed to a single dose of CCl4 (50 mg/kg, IP) and euthanized at different time points. Liver histology, blood alanine aminotransferase, and other enzyme activities were measured in CCl4-exposed mice without or with the highly-specific JNK inhibitors. Phosphoproteins were purified from control or CCl4-exposed mice and analyzed by differential mass-spectrometry followed by further characterizations of immunoprecipitation and activity measurements. JNK was activated within 1 h while liver damage was maximal at 24 h post-CCl4 injection. Markedly increased phosphorylation of many mitochondrial proteins was observed between 1 and 8 h following CCl4 exposure. Pretreatment with the selective JNK inhibitor SU3327 or the mitochondria-targeted antioxidant mito-TEMPO markedly reduced the levels of p-JNK, mitochondrial phosphoproteins and liver damage in CCl4-exposed mice. Differential proteomic analysis identified many phosphorylated mitochondrial proteins involved in anti-oxidant defense, electron transfer, energy supply, fatty acid oxidation, etc. Aldehyde dehydrogenase, NADH-ubiquinone oxidoreductase, and alpha-ketoglutarate dehydrogenase were phosphorylated in CCl4-exposed mice but dephosphorylated after SU3327 pretreatment. Consistently, the suppressed activities of these enzymes were restored by SU3327 pretreatment in CCl4-exposed mice. These data provide a novel mechanism by which JNK, rapidly activated by CCl4, promotes mitochondrial dysfunction and acute hepatotoxicity through robust phosphorylation of numerous mitochondrial proteins. Published by Elsevier B.V.
C1 [Jang, Sehwan; Abdelmegeed, Mohamed A.; Banerjee, Atrayee; Song, Byoung-Joon] NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA.
[Yu, Li-Rong; Gao, Yuan] US FDA, Biomarkers & Alternat Models Branch, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Song, BJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA.
EM sehwan.jang@upr.edu; abdelmegeedm@mail.nih.gov; yuangao2000@gmail.com;
atrayee.liver@gmail.com; bj.song@nih.gov
FU Intramural Research Program of National Institute of Alcohol Abuse and
Alcoholism (NIAAA); Intramural Fund of National Center for Toxicological
Research, U.S. Food and Drug Administration (NCTR/FDA)
FX This study was supported by the Intramural Research Program of National
Institute of Alcohol Abuse and Alcoholism (NIAAA) and in part with funds
from the Intramural Fund of National Center for Toxicological Research,
U.S. Food and Drug Administration (NCTR/FDA). The views presented in
this article do not necessarily reflect those of the U.S. Food and Drug
Administration. The authors are also grateful to Drs. Youngshim Choi and
Klaus Gawrisch for the excellent technical help and support for this
study, respectively.
NR 59
TC 8
Z9 8
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2213-2317
J9 REDOX BIOL
JI Redox Biol.
PD DEC
PY 2015
VL 6
BP 552
EP 564
DI 10.1016/j.redox.2015.09.040
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CZ8GR
UT WOS:000367338700054
PM 26491845
ER
PT J
AU Witten, CM
McFarland, RD
Simek, SL
AF Witten, Celia M.
McFarland, Richard D.
Simek, Stephanie L.
TI Concise Review: The US Food and Drug Administration and Regenerative
Medicine
SO STEM CELLS TRANSLATIONAL MEDICINE
LA English
DT Review
DE Regenerative medicine; Tissue engineering; US Food and Drug
Administration; Regulation
AB Regenerative medicine (RM) is a popular term for a field of scientific and medical research. There is not one universally accepted definition of RM, but it is generally taken to mean the translation of multidisciplinary biology and engineering science into therapeutic approaches to regenerate, replace, or repair tissues and organs. RM products have the potential to provide treatments for a number of unmet needs but have substantial scientific and regulatory challenges that need to be addressed for this potential to be fully realized. FDA has established formal regulatory definitions for biologics, medical devices, and combination products, as well as human cells and tissues. Regenerative medicine products regulated by FDA are classified on the basis of these definitions, and the classification forms the basis for determining the regulatory requirements to each specific product. FDA regulations are generally written to allow the agency flexibility to accommodate new scientific questions raised by novel and evolving technologies. FDA efforts to facilitate product development in this novel and promising area include working with individual sponsors, interacting with the scientific and industry communities, participating in standards development, and developing policy and guidance.
C1 [Witten, Celia M.; McFarland, Richard D.; Simek, Stephanie L.] US FDA, Ctr Biol Evaluat & Res, Off Cellular Tissue & Gene Therapies, Silver Spring, MD 20993 USA.
RP Witten, CM (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Cellular Tissue & Gene Therapies, 10903 New Hampshire Ave,Bldg 71,Room 5230, Silver Spring, MD 20993 USA.
EM celia.witten@fda.hhs.gov
NR 8
TC 0
Z9 1
U1 2
U2 9
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 2157-6564
EI 2157-6580
J9 STEM CELL TRANSL MED
JI Stem Cells Transl. Med.
PD DEC
PY 2015
VL 4
IS 12
BP 1495
EP 1499
DI 10.5966/sctm.2015-0098
PG 5
WC Cell & Tissue Engineering
SC Cell Biology
GA CZ9NO
UT WOS:000367424500019
PM 26494784
ER
PT J
AU Ng, W
Doughty, SW
Luo, H
Ye, H
Ge, WG
Tong, WD
Hong, HX
AF Hui Wen Ng
Doughty, Stephen W.
Luo, Heng
Ye, Hao
Ge, Weigong
Tong, Weida
Hong, Huixiao
TI Development and Validation of Decision Forest Model for Estrogen
Receptor Binding Prediction of Chemicals Using Large Data Sets
SO CHEMICAL RESEARCH IN TOXICOLOGY
LA English
DT Article
ID ENDOCRINE-DISRUPTING CHEMICALS; IN-VITRO ASSAYS; ENVIRONMENTAL
CHEMICALS; DIVERSE CHEMICALS; ANDROGEN RECEPTOR; ALPHA-FETOPROTEIN;
STRUCTURAL DIVERSITY; MOLECULAR DOCKING; TOXCAST PROGRAM; PHASE-II
AB Some chemicals in the environment possess the potential to interact with the endocrine system in the human body. Multiple receptors are involved in the endocrine system; estrogen receptor alpha (ER alpha) plays very important roles in endocrine activity and is the most studied receptor. Understanding and predicting estrogenic activity of chemicals facilitates the evaluation of their endocrine activity. Hence, we have developed a decision forest classification model to predict chemical binding to ER alpha using a large training data set of 3308 chemicals obtained from the U.S. Food and Drug Administration's Estrogenic Activity Database. We tested the model using cross validations and external data sets of 1641 chemicals obtained from the U.S. Environmental Protection Agency's ToxCast project. The model showed good performance in both internal (92% accuracy) and external validations (similar to 70-89% relative balanced accuracies), where the latter involved the validations of the model across different ER pathway-related assays in ToxCast. The important features that contribute to the prediction ability of the model were identified through informative descriptor analysis and were related to current knowledge of ER binding. Prediction confidence analysis revealed that the model had both high prediction confidence and accuracy for most predicted chemicals. The results demonstrated that the model constructed based on the large training data set is more accurate and robust for predicting ER binding of chemicals than the published models that have been developed using much smaller data sets. The model could be useful for the evaluation of ER alpha-mediated endocrine activity potential of environmental chemicals.
C1 [Hui Wen Ng; Luo, Heng; Ye, Hao; Ge, Weigong; Tong, Weida; Hong, Huixiao] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Doughty, Stephen W.] Univ Nottingham Malaysia Campus, Sch Pharm, Semenyih 43500, Selangor, Malaysia.
RP Hong, HX (reprint author), US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM huixiao.hong@fda.hhs.gov
RI Luo, Heng/D-3616-2016
OI Luo, Heng/0000-0001-5192-8878
FU NCTR
FX The work for this article was funded by NCTR-appropriated funds. This
research was supported in part by an appointment to the Research
Participation Program at the National Center for Toxicological Research
(H.W.N. and H.Y.) administered by the Oak Ridge Institute for Science
and Education through an interagency agreement between the U.S.
Department of Energy and the U.S. Food and Drug Administration.
NR 41
TC 6
Z9 6
U1 2
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0893-228X
EI 1520-5010
J9 CHEM RES TOXICOL
JI Chem. Res. Toxicol.
PD DEC
PY 2015
VL 28
IS 12
BP 2343
EP 2351
DI 10.1021/acs.chemrestox.5b00358
PG 9
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology
SC Pharmacology & Pharmacy; Chemistry; Toxicology
GA CZ5BT
UT WOS:000367118000012
ER
PT J
AU Kachko, A
Frey, SE
Sirota, L
Ray, R
Wells, F
Zubkova, I
Zhang, P
Major, ME
AF Kachko, Alla
Frey, Sharon E.
Sirota, Lev
Ray, Ranjit
Wells, Frances
Zubkova, Iryna
Zhang, Pei
Major, Marian E.
TI Antibodies to an Interfering Epitope in Hepatitis C Virus E2 Can Mask
Vaccine-Induced Neutralizing Activity
SO HEPATOLOGY
LA English
DT Article
ID HUMAN MONOCLONAL-ANTIBODIES; ENVELOPE GLYCOPROTEIN; MEDIATED
NEUTRALIZATION; ELICITS ANTIBODIES; AMINO-TERMINUS; PROTEIN; INFECTION;
AP33; HCV; NONNEUTRALIZATION
AB Hepatitis C virus (HCV) neutralization occurring at the E2 region 412-426 (EP-I) could be enhanced when antibodies directed specifically to the E2 region 434-446 (EP-II) were removed from serum samples of persistently infected patients and vaccinated chimpanzees, a phenomenon of so-called antibody interference. Here, we show that this type of interference can be observed in individuals after immunization with recombinant E1E2 proteins. One hundred twelve blinded serum samples from a phase I, placebo-controlled, dose escalation trial using recombinant HCV E1E2 with MF59C.1 adjuvant in healthy HCV-negative adults were tested in enzyme-linked immunosorbent assay for binding reactivity to peptides representing the E2 regions 412-426 (EP-I) and 434-446 (EP-II). All samples were subsequently tested for neutralizing activity using cell-culture HCV 1a(H77)/2a chimera, HCV pseudotype particles (HCVpp) H77, and HCVpp HCV-1 after treatment to remove EP-II-specific antibodies or mock treatment with a control peptide. Among the 112 serum samples, we found 22 double positive (EP-I and EP-II), 6 EP-II positive only, 14 EP-I positive only, and 70 double negative. Depleting EP-II antibodies from double-positive serum samples increased 50% inhibitory dose (ID50) neutralizing antibody titers (up to 4.9-fold) in up to 72% of samples (P <= 0.0005), contrasting with ID50 neutralization titer increases in 2 of 70 double-negative samples (2.9%; P > 0.5). In addition, EP-I-specific antibody levels in serum samples showed a significant correlation with ID50 neutralization titers when EP-II antibodies were removed (P < 0.0003). Conclusion: These data show that antibodies to the region 434-446 are induced during immunization of individuals with recombinant E1E2 proteins, and that these antibodies can mask effective neutralizing activity from EP-I-specific antibodies. Elicitation of EP-II-specific antibodies with interfering capacity should be avoided in producing an effective cross-neutralizing vaccine aimed at the HCV-envelope proteins.
C1 [Kachko, Alla; Wells, Frances; Zubkova, Iryna; Major, Marian E.] US FDA, Div Viral Prod, CBER, Silver Spring, MD 20993 USA.
[Frey, Sharon E.; Ray, Ranjit] St Louis Univ, Sch Med, Div Infect Dis Allergy & Immunol, St Louis, MO USA.
[Sirota, Lev] US FDA, Div Biostat, Off Biostat & Epidemiol, CBER, Silver Spring, MD 20993 USA.
[Zhang, Pei] US FDA, Div Hematol, CBER, Silver Spring, MD 20993 USA.
RP Major, ME (reprint author), US FDA, Div Viral Prod, CBER, Bldg 52-72-Room 1210,10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM marian.major@fda.hhs.gov
FU U.S. Food and Drug Administration [Z01 BK 04010-11 LHV]; [NO1-AI-25464]
FX The studies described were supported with U.S. Food and Drug
Administration intramural funds (program no.: Z01 BK 04010-11 LHV). The
clinical trial DMID 01-002 (ClinicalTrials.gov identifier: NCT00500747)
was funded under contract NO1-AI-25464.
NR 45
TC 3
Z9 3
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD DEC
PY 2015
VL 62
IS 6
BP 1670
EP 1682
DI 10.1002/hep.28108
PG 13
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CZ3OF
UT WOS:000367013200040
PM 26251214
ER
PT J
AU Turner, AD
Higgins, C
Higman, W
Hungerford, J
AF Turner, Andrew D.
Higgins, Cowan
Higman, Wendy
Hungerford, James
TI Potential Threats Posed by Tetrodotoxins in UK Waters: Examination of
Detection Methodology Used in Their Control
SO MARINE DRUGS
LA English
DT Review
DE tetrodotoxins; shellfish; pufferfish poisoning; TTX
ID TANDEM MASS-SPECTROMETRY; PERFORMANCE LIQUID-CHROMATOGRAPHY; SHELLFISH
POISONING TOXINS; PLEUROBRANCHAEA-MACULATA GASTROPODA; TISSUE-CULTURE
BIOASSAY; RECEPTOR-BINDING ASSAY; MARINE PUFFER FISH; RED-SPOTTED NEWT;
STYLOCHOPLANA SP.; LC-MS/MS
AB Tetrodotoxin is a neurotoxin responsible for many human fatalities, most commonly following the consumption of pufferfish. Whilst the source of the toxin has not been conclusively proven, it is thought to be associated with various species of marine bacteria. Whilst the toxins are well studied in fish and gastropods, in recent years, there have been a number of reports of tetrodotoxin occurring in bivalve shellfish, including those harvested from the UK and other parts of Europe. This paper reviews evidence concerning the prevalence of tetrodotoxins in the UK together with methodologies currently available for testing. Biological, biomolecular and chemical methods are reviewed, including recommendations for further work. With the recent development of quantitative chromatographic methods for these and other hydrophilic toxins, as well as the commercial availability of rapid testing kits, there are a number of options available to ensure consumers are protected against this threat.
C1 [Turner, Andrew D.; Higman, Wendy] Ctr Environm Fisheries & Aquaculture Sci Cefas, Weymouth DT4 8UB, Dorset, England.
[Higgins, Cowan] Agrifood & Biosc Inst AFBI, Belfast BT9 5PX, Antrim, North Ireland.
[Hungerford, James] US FDA, Pacific Lab NW, Bothell, WA 98021 USA.
RP Turner, AD (reprint author), Ctr Environm Fisheries & Aquaculture Sci Cefas, Barrack Rd, Weymouth DT4 8UB, Dorset, England.
EM Andrew.turner@cefas.co.uk; cowan_higgins@msn.com;
Wendy.higman@cefas.co.uk; James.hungerford@fda.hhs.gov
FU Food Standards Scotland [FS513005]
FX The authors thank Food Standards Scotland who funded this review
(contract code FS513005).
NR 115
TC 1
Z9 1
U1 9
U2 24
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1660-3397
J9 MAR DRUGS
JI Mar. Drugs
PD DEC
PY 2015
VL 13
IS 12
BP 7357
EP 7376
DI 10.3390/md13127070
PG 20
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA CZ4CD
UT WOS:000367049700015
PM 26690455
ER
PT J
AU Liu, JB
Jiang, XM
Wang, LM
Hu, ZJ
Wen, T
Liu, WQ
Yin, JJ
Chen, CY
Wu, XC
AF Liu, Jianbo
Jiang, Xiumei
Wang, Liming
Hu, Zhijian
Wen, Tao
Liu, Wenqi
Yin, Junjie
Chen, Chunying
Wu, Xiaochun
TI Ferroxidase-like activity of Au nanorod/Pt nanodot structures and
implications for cellular oxidative stress
SO NANO RESEARCH
LA English
DT Article
DE Au@Pt nanostructure; ferroxidase; peroxidase; antioxidant activity;
biological effect
ID PEROXIDASE-LIKE ACTIVITY; ENZYME-LIKE ACTIVITIES; AT-PT NANOSTRUCTURES;
ARTIFICIAL ENZYMES; PLATINUM NANOPARTICLES; COLORIMETRIC DETECTION;
CATALYTIC-ACTIVITY; SUPEROXIDE ANION; IRON-METABOLISM; GRAPHENE OXIDE
AB Platinum nanoparticles (NPs) are reported to mimic various antioxidant enzymes and thus may produce a positive biological effect by reducing reactive oxygen species (ROS) levels. In this manuscript, we report Pt NPs as an enzyme mimic of ferroxidase by depositing platinum nanodots on gold nanorods (Au@Pt NDRs). Au@Pt NDRs show pH-dependent ferroxidase-like activity and have higher activity at neutral pH values. Cytotoxicity results with human cell lines (lung adenocarcinoma A549 and normal bronchial epithelial cell line HBE) show that Au@Pt NDRs are taken up into cells via endocytosis and translocate into the endosome/lysosome. Au@Pt NDRs have good biocompatibility at NDR particle concentrations lower than 0.15 nIe. However, in the presence of H2O2, lysosomelocated NDRs exhibit peroxidase-like activity and therefore increase cytotoxicity. In the presence of Fe2+, the ferroxidase-like activity of the NDRs protects cells from oxidative stress by consuming H2O2. Thorough consideration should be given to this behavior when employing Au@Pt NDRs in biological systems.
C1 [Liu, Jianbo; Hu, Zhijian; Wen, Tao; Liu, Wenqi; Wu, Xiaochun] Chinese Acad Sci, Natl Ctr Nanosci & Technol, Key Lab Standardizat & Measurement Nanotechnol, Beijing 100190, Peoples R China.
[Liu, Jianbo] Zaozhuang Univ, Coll Optoelect Engn, Zaozhuang 277100, Peoples R China.
[Jiang, Xiumei; Wang, Liming; Chen, Chunying] Chinese Acad Sci, Natl Ctr Nanosci & Technol, Key Lab Biol Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China.
[Wen, Tao; Yin, Junjie] US FDA, Div Analyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
RP Yin, JJ (reprint author), US FDA, Div Analyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
EM junjie.yin@fda.hhs.gov; chenchy@nanoctr.cn; wuxc@nanoctr.cn
RI Yin, Jun Jie /E-5619-2014; Wang, Liming/A-6924-2012
OI Wang, Liming/0000-0003-1382-9195
FU National Natural Science Foundation of China [21173056, 31070854];
National Basic Research Program of China [2012CB934001, 2011CB933401];
regulatory science grant under the FDA Nanotechnology CORES Program
FX The work was supported by the National Natural Science Foundation of
China (Nos. 21173056 and 31070854) and the National Basic Research
Program of China (Nos. 2012CB934001 and 2011CB933401). J. J. Y.
acknowledged partial support from a regulatory science grant under the
FDA Nanotechnology CORES Program. This article is not an official U.S.
FDA guidance or policy statement. No official support or endorsement by
the U.S. FDA is intended or should be inferred.
NR 42
TC 3
Z9 3
U1 21
U2 67
PU TSINGHUA UNIV PRESS
PI BEIJING
PA TSINGHUA UNIV, RM A703, XUEYAN BLDG, BEIJING, 10084, PEOPLES R CHINA
SN 1998-0124
EI 1998-0000
J9 NANO RES
JI Nano Res.
PD DEC
PY 2015
VL 8
IS 12
BP 4024
EP 4037
DI 10.1007/s12274-015-0904-x
PG 14
WC Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science,
Multidisciplinary; Physics, Applied
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA CZ3KQ
UT WOS:000367003400027
ER
PT J
AU Xu, YQ
Ma, L
Norton, MG
Stuart, C
Zhao, Z
Toibero, D
Dahlen, S
Zhong, LL
Zhang, P
Struble, EB
AF Xu, Yanqun
Ma, Li
Norton, Malgorzata G.
Stuart, Christine
Zhao, Zhong
Toibero, Denise
Dahlen, Shelby
Zhong, Lilin
Zhang, Pei
Struble, Evi B.
TI Gestation age dependent transfer of human immunoglobulins across
placenta in timed-pregnant guinea pigs
SO PLACENTA
LA English
DT Article
DE Transplacental immunoglobulin transfer
ID NEONATAL FC-RECEPTOR; IGG TRANSPORT; SUBCLASSES; MOTHER; PROTEINS;
FETUS; MICE
AB Introduction: When administered during pregnancy, antibodies and other biologic drugs that contain the Fc part of the IgG molecule can traverse the placenta. Although it is generally accepted that the FcRn receptor mediates this process, gaps remain in our understanding of underlying details in humans and in common laboratory animal species.
Methods: We expanded our previous studies in timed-pregnant guinea pigs to both measure the transport of human (h) IgG at earlier gestation ages in vivo and evaluate FcRn function in vitro using Surface Plasmon Resonance (SPR) and Madin-Darby canine kidney cells (MDCK) that express guinea pig (gp) FcRn.
Results: In timed-pregnant guinea pigs both the average concentration of hIgG in the fetus and its ratio to maternal hIgG concentration increase exponentially with gestation age. Thus, hIgG fetal:maternal concentration ratios increase from an average of 1% to 3%, 17%, and 76% on GD similar to 26, 35, 46, and 54, respectively. In vitro, gpFcRn immobilized on a solid surface can bind hIgG and gpIgG preparations in a similar manner. All engineered human Fc isotype-specific constructs were internalized by MDCK-gpFcRn cells at significant levels. While not significant, their recycling and hIgG transcytosis by this cell line also trend higher than background controls.
Discussion: Pregnant guinea pigs exhibit similarities with humans in the degree and timing of transplacental transfer as well as the ability of their FcRn to bind and internalize hIgG in vitro. Further studies are needed to guide building appropriate systems for the evaluation of FcRn mediated function of human immunoglobulin therapies. Published by Elsevier Ltd.
C1 [Xu, Yanqun; Ma, Li; Norton, Malgorzata G.; Stuart, Christine; Zhao, Zhong; Toibero, Denise; Dahlen, Shelby; Zhong, Lilin; Zhang, Pei; Struble, Evi B.] US FDA, Div Hematol Res & Review, Off Blood Res & Review, CBER, Rockville, MD 20857 USA.
RP Struble, EB (reprint author), 10903 New Hampshire Ave,Bldg 52-72, Silver Spring, MD 20993 USA.
EM evi.struble@fda.hhs.gov
NR 27
TC 1
Z9 1
U1 0
U2 0
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0143-4004
EI 1532-3102
J9 PLACENTA
JI Placenta
PD DEC
PY 2015
VL 36
IS 12
BP 1370
EP 1377
DI 10.1016/j.placenta.2015.10.018
PG 8
WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
GA CZ2QU
UT WOS:000366950500005
PM 26578159
ER
PT J
AU Roberts, RA
Aschner, M
Calligaro, D
Guilarte, TR
Hanig, JP
Herr, DW
Hudzik, TJ
Jeromin, A
Kallman, MJ
Liachenko, S
Lynch, JJ
Miller, DB
Moser, VC
O'Callaghan, JP
Slikker, W
Paule, MG
AF Roberts, Ruth A.
Aschner, Michael
Calligaro, David
Guilarte, Tomas R.
Hanig, Joseph P.
Herr, David W.
Hudzik, Thomas J.
Jeromin, Andreas
Kallman, Mary J.
Liachenko, Serguei
Lynch, James J., III
Miller, Diane B.
Moser, Virginia C.
O'Callaghan, James P.
Slikker, William, Jr.
Paule, Merle G.
TI Translational Biomarkers of Neurotoxicity: A Health and Environmental
Sciences Institute Perspective on the Way Forward
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE neurotoxicity; biomarker; imaging; CSF; neurotoxicity
ID TRAUMATIC BRAIN-INJURY; CEREBROSPINAL-FLUID BIOMARKERS; C-TERMINAL
HYDROLASE-L1; 18 KDA TSPO; MULTIPLE-SCLEROSIS; IN-VIVO;
ALZHEIMERS-DISEASE; TRIMETHYLTIN; RAT; NEURODEGENERATION
AB Neurotoxicity has been linked to a number of common drugs and chemicals, yet efficient and accurate methods to detect it are lacking. There is a need for more sensitive and specific biomarkers of neurotoxicity that can help diagnose and predict neurotoxicity that are relevant across animal models and translational from nonclinical to clinical data. Fluid-based biomarkers such as those found in serum, plasma, urine, and cerebrospinal fluid (CSF) have great potential due to the relative ease of sampling compared with tissues. Increasing evidence supports the potential utility of fluid-based biomarkers of neurotoxicity such as microRNAs, F-2-isoprostanes, translocator protein, glial fibrillary acidic protein, ubiquitin C-terminal hydrolase L1, myelin basic protein, microtubule-associated protein-2, and total tau. However, some of these biomarkers such as those in CSF require invasive sampling or are specific to one disease such as Alzheimer's, while others require further validation. Additionally, neuroimaging methodologies, including magnetic resonance imaging, magnetic resonance spectroscopy, and positron emission tomography, may also serve as potential biomarkers and have several advantages including being minimally invasive. The development of biomarkers of neurotoxicity is a goal shared by scientists across academia, government, and industry and is an ideal topic to be addressed via the Health and Environmental Sciences Institute (HESI) framework which provides a forum to collaborate on key challenging scientific topics. Here we utilize the HESI framework to propose a consensus on the relative potential of currently described biomarkers of neurotoxicity to assess utility of the selected biomarkers using a nonclinical model.
C1 [Roberts, Ruth A.] ApconiX, BioHub Alderley Pk, Macclesfield SK10 4TG, Cheshire, England.
[Aschner, Michael] Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA.
[Calligaro, David] Eli Lilly & Co, Div Eli Lilly & Co, Pharmacol Toxicol Res Lilly Res Labs, Lilly Corp Ctr, Indianapolis, IN 46285 USA.
[Guilarte, Tomas R.] Columbia Univ, New York, NY 10032 USA.
[Hanig, Joseph P.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Herr, David W.; Moser, Virginia C.] US EPA, NHEERL, Toxicol Assessment Div, Res Triangle Pk, NC 27711 USA.
[Hudzik, Thomas J.] AbbVie Inc, N Chicago, IL 60064 USA.
[Jeromin, Andreas; Lynch, James J., III] Quanterix Inc, Lexington, MA 02421 USA.
[Kallman, Mary J.] Covance Inc, Indianapolis, IN 46214 USA.
[Liachenko, Serguei; Slikker, William, Jr.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Miller, Diane B.; O'Callaghan, James P.] NIOSH, Ctr Dis Control & Prevent, Morgantown, WV 26505 USA.
[Paule, Merle G.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA.
RP Roberts, RA (reprint author), ApconiX, BioHub Alderley Pk, Macclesfield SK10 4TG, Cheshire, England.
EM ruth.roberts@apconix.com
FU NIEHS NIH HHS [P30 ES009089]
NR 53
TC 2
Z9 2
U1 4
U2 19
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD DEC
PY 2015
VL 148
IS 2
BP 332
EP 340
DI 10.1093/toxsci/kfv188
PG 9
WC Toxicology
SC Toxicology
GA CZ6FB
UT WOS:000367195500001
PM 26609132
ER
PT J
AU Rebuli, ME
Camacho, L
Adonay, ME
Reif, DM
Aylor, DL
Patisaul, HB
AF Rebuli, Meghan E.
Camacho, Luisa
Adonay, Maria E.
Reif, David M.
Aylor, David L.
Patisaul, Heather B.
TI Impact of Low-Dose Oral Exposure to Bisphenol A (BPA) on Juvenile and
Adult Rat Exploratory and Anxiety Behavior: A CLARITY-BPA Consortium
Study
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE bisphenol A; CLARITY; behavior; anxiety; exploratory activity; endocrine
disruption; EDC; sexually dimorphic; brain; BPA; plastic
ID SPRAGUE-DAWLEY RATS; ELEVATED PLUS-MAZE; ESTROGEN-RECEPTOR EXPRESSION;
ENDOCRINE ACTIVE COMPOUNDS; OPEN-FIELD BEHAVIOR; SEX-DIFFERENCES;
ETHINYL ESTRADIOL; DEVELOPMENTAL TREATMENT; FEMALE RATS; PERINATAL
EXPOSURE
AB Bisphenol A ( BPA) is a high volume production chemical and has been identified as an endocrine disruptor, prompting concern that developmental exposure could impact brain development and behavior. Rodent and human studies suggest that early life BPA exposuremay result in an anxious, hyperactive phenotype but results are conflicting and data from studies using multiple doses below the no- observed- adverse- effect level are limited. To address this, the present studies were conducted as part of the CLARITY- BPA ( Consortium Linking Academic and Regulatory Insights on BPA Toxicity) program. The impact of perinatal BPA exposure ( 2.5, 25, or 2500 mu g/ kg body weight ( bw)/ day) on behaviors related to anxiety and exploratory activity was assessed in juvenile ( prepubertal) and adult NCTR Sprague- Dawley rats of both sexes. Ethinyl estradiol ( 0.5 mu g/ kg bw/ day) was used as a reference estrogen. Exposure spanned gestation and lactation with dams gavaged from gestational day 6 until birth and then the offspring gavaged directly through weaning ( n = 12/ sex/ group). Behavioral assessments included open field, elevated plus maze, and zero maze. Anticipated sex differences in behavior were statistically identified or suggested inmost cases. No consistent effects of BPA were observed for any endpoint, in either sex, at either age compared to vehicle controls; however, significant differences between BPA- exposed and ethinyl estradiol- exposed groups were identified for some endpoints. Limitations of this study are discussed and include suboptimal statistical power and low concordance across behavioral tasks. These data do not indicate BPA- related effects on anxiety or exploratory activity in these developmentally exposed rats.
C1 [Rebuli, Meghan E.; Reif, David M.; Aylor, David L.; Patisaul, Heather B.] N Carolina State Univ, Dept Biol Sci, Raleigh, NC 27695 USA.
[Rebuli, Meghan E.; Patisaul, Heather B.] N Carolina State Univ, Keck Ctr Behav Biol, Raleigh, NC 27695 USA.
[Camacho, Luisa] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Adonay, Maria E.; Reif, David M.; Aylor, David L.] N Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC 27695 USA.
RP Rebuli, ME (reprint author), N Carolina State Univ, Dept Biol Sci, Raleigh, NC 27695 USA.
EM hbpatisa@ncsu.edu
OI Reif, David/0000-0001-7815-6767
FU NIEHS [U011ES020929]; NIEHS Interagency Agreement [AES12013 (FDA IAG
224-12-0003)]; NIH [P42ES005948, R01ES19604]
FX This study is part of the NIEHS CLARITY-BPA Consortium supported by
NIEHS grant U011ES020929 to H.B.P., and the animal portion of this study
is supported by NIEHS Interagency Agreement AES12013 (FDA IAG
224-12-0003). This study was also supported by NIH P42ES005948 and NIH
R01ES19604 to D.M.R.
NR 106
TC 6
Z9 6
U1 16
U2 32
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD DEC
PY 2015
VL 148
IS 2
BP 341
EP 354
DI 10.1093/toxsci/kfv163
PG 14
WC Toxicology
SC Toxicology
GA CZ6FB
UT WOS:000367195500002
PM 26209558
ER
PT J
AU Deuel, JW
Vallelian, F
Schaer, CA
Puglia, M
Buehler, PW
Schaer, DJ
AF Deuel, Jeremy W.
Vallelian, Florence
Schaer, Christian A.
Puglia, Michele
Buehler, Paul W.
Schaer, Dominik J.
TI Different target specificities of haptoglobin and hemopexin define a
sequential protection system against vascular hemoglobin toxicity
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Hemolysis; Hemoglobin; Haptoglobin; Hemopexin; Lipoprotein; Lipid
oxidation; Endothelial cell
ID LOW-DENSITY-LIPOPROTEIN; MASS-SPECTROMETRY DEFINES; RED-BLOOD-CELL;
GUINEA-PIGS; HEMOLYTIC DISEASES; HEME UPTAKE; OXIDATION; DAMAGE;
ACTIVATION; MECHANISM
AB Free hemoglobin (Hb) triggered vascular damage occurs in many hemolytic diseases, such as sickle cell disease, with an unmet need for specific therapeutic interventions. Based on clinical observations the Hb and heme scavenger proteins haptoglobin (Hp) and hemopexin (Hx) have been characterized as a sequential defense system with Hp as the primary protector and Hx as a backup when all Hp is depleted during more severe intravascular hemolysis. In this study we present a mechanistic rationale for this paradigm based on a combined biochemical and cell biological approach directed at understanding the unique roles of Hp and Hx in Hb detoxification. Using a novel in vitro model of Hb triggered endothelial damage, which recapitulates the well-characterized pathophysiologic sequence of oxyHb(Fe2+) transformation to ferric Hb(Fe3+), free heme transfer from ferric Hb(Fe3+) to lipoprotein and subsequent oxidative reactions in the lipophilic phase. The accumulation of toxic lipid peroxidation products liberated during oxidation reactions ultimately lead to endothelial damage characterized by a specific gene expression pattern with reduced cellular ATP and monolayer disintegration. Quantitative analysis of key chemical and biological parameters allowed us to precisely define the mechanisms and concentrations required for Hp and Hx to prevent this toxicity. In the case of Hp we defined an exponential relationship between Hp availability relative to oxyHb(Fe2+) and related protective activity. This exponential relationship demonstrates that large Hp quantities are required to prevent Hb toxicity. In contrast, the linear relationship between Hx concentration and protection defines a highly efficient backup scavenger system during conditions of large excess of free oxyHb(Fe2+) that occurs when all Hp is consumed. The diverse protective function of Hp and Hx in this model can be explained by the different target specificities of the two proteins. (C) 2015 The Authors. Published by Elsevier Inc.
C1 [Deuel, Jeremy W.; Vallelian, Florence; Schaer, Christian A.; Puglia, Michele; Schaer, Dominik J.] Univ Zurich Hosp, Div Internal Med, CH-8091 Zurich, Switzerland.
[Puglia, Michele] Univ Zurich, Funct Genom Ctr, CH-8006 Zurich, Switzerland.
[Buehler, Paul W.] US FDA, CBER, Silver Spring, MD USA.
RP Schaer, DJ (reprint author), Univ Zurich Hosp, Div Internal Med, Ramistr 100, CH-8091 Zurich, Switzerland.
EM dominik.schaer@usz.ch
FU Swiss National Science Foundation [310030/120658, 31003A/138500];
University of Zurich Research Priority Program "Integrative Human
Physiology"; Swiss Federal Commission for Technology and Innovation
(CTI)
FX This work was supported by the Swiss National Science Foundation (grants
310030/120658 and 31003A/138500 to DJS), the University of Zurich
Research Priority Program "Integrative Human Physiology" and the Swiss
Federal Commission for Technology and Innovation (CTI).
NR 36
TC 8
Z9 8
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD DEC
PY 2015
VL 89
BP 931
EP 943
DI 10.1016/j.freeradbiomed.2015.09.016
PG 13
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA CY4CI
UT WOS:000366355800087
PM 26475040
ER
PT J
AU Gonzalez, EA
Nandy, P
Lucas, AD
Hitchins, VM
AF Gonzalez, Elizabeth A.
Nandy, Poulomi
Lucas, Anne D.
Hitchins, Victoria M.
TI Ability of cleaning-disinfecting wipes to remove bacteria from medical
device surfaces
SO AMERICAN JOURNAL OF INFECTION CONTROL
LA English
DT Article
DE Reusable medical devices; Cleaning; Disinfection; Nosocomial infection
ID RESISTANT ACINETOBACTER-BAUMANNII; PSEUDOMONAS-AERUGINOSA;
CLOSTRIDIUM-DIFFICILE; STAPHYLOCOCCUS-AUREUS; NOSOCOMIAL OUTBREAK;
INFECTION; CONTAMINATION; COLONIZATION; DIARRHEA; COSTS
AB Background: Nosocomial infections are a serious problem in health care facilities. Bacteria can be transferred from patient to patient via contaminated reusable medical devices and equipment.
Methods: An anesthesia machine and objects representative of smooth and ridged machine knobs were contaminated with Staphylococcus aureus, Bacillus atrophaeus spores, and Clostridium sporogenes spores. The ability of 5 commercially available cleaning-disinfecting wipes to remove bacteria was compared with gauze soaked with water or bleach. Gauze soaked with water was used to determine the optimal wetness for bacteria removal, which was then used to evaluate the efficacy of the wipe ingredients.
Results: All of the wipes cleaned the device surfaces significantly better than the no wipe control. Some wipes performed equally well as gauze with water, whereas others performed worse. Overall, the wipe containing sodium hypochlorite was the most effective at removing bacteria. When the wipe ingredients were re-evaluated using the determined optimal wipe wetness on gauze, their effectiveness at cleaning S aureus, but not spores, significantly improved.
Conclusion: Physically removing bacteria from device surfaces with water was often as effective as the cleaning-disinfecting wipes. Of the wipe active ingredients evaluated, sodium hypochlorite was the most effective overall. The wetness of the wipes may also play a role in their effectiveness. Published by Elsevier Inc. on behalf of the Association for Professionals in Infection Control and Epidemiology, Inc.
C1 [Gonzalez, Elizabeth A.; Nandy, Poulomi; Lucas, Anne D.; Hitchins, Victoria M.] US FDA, Div Biol Chem & Mat Sci, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Gonzalez, EA (reprint author), 10903 New Hampshire Ave,Bldg 64,Rm 4022, Silver Spring, MD 20993 USA.
EM Elizabeth.gonzalez@fda.hhs.gov
FU U.S. Food and Drug Administration's Medical Countermeasures Initiative;
U.S. Department of Energy; U.S. Food and Drug Administration
FX This work was supported in part by an appointment to the Research
Participation Program at the Center for Devices and Radiological Health
administered by the Oak Ridge Institute for Science and Education
through an interagency agreement between the U.S. Department of Energy
and the U.S. Food and Drug Administration and from the U.S. Food and
Drug Administration's Medical Countermeasures Initiative.
NR 25
TC 1
Z9 1
U1 0
U2 12
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-6553
EI 1527-3296
J9 AM J INFECT CONTROL
JI Am. J. Infect. Control
PD DEC 1
PY 2015
VL 43
IS 12
BP 1331
EP 1335
DI 10.1016/j.ajic.2015.07.024
PG 5
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA CX9EU
UT WOS:000366008600018
PM 26654235
ER
PT J
AU Rostron, BL
Chang, CM
van Bemmel, DM
Xia, Y
Blount, BC
AF Rostron, Brian L.
Chang, Cindy M.
van Bemmel, Dana M.
Xia, Yang
Blount, Benjamin C.
TI Nicotine and Toxicant Exposure among US Smokeless Tobacco Users: Results
from 1999 to 2012 National Health and Nutrition Examination Survey Data
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID HIGH-SCHOOL-STUDENTS; UNITED-STATES; CIGARETTE SMOKERS; CARCINOGEN;
PRODUCTS; BIOMARKERS; NITROSAMINES; SURVEILLANCE; ELIMINATION;
POPULATION
AB Background: It has been suggested that smokeless tobacco users have high nicotine and toxicant exposure, but studies with nationally representative data have been limited.
Methods: We analyzed biomarkers of tobacco exposure for 23,684 adult participants from the National Health and Nutrition Examination Survey from 1999 to 2012. The biomarkers analyzed were serum cotinine, urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), blood lead, blood cadmium, blood mercury, urinary arsenic, and urinary N-acetyl-S-(2-cyanoethyl)-L-cysteine. We calculated geometric mean concentrations for each biomarker by tobacco use category and geometric mean ratios adjusting for demographic factors.
Results: Exclusive smokeless tobacco users had higher geometric mean concentrations of serum cotinine [178.9 ng/mL, 95% confidence interval (CI), 145.5-220.0] and NNAL (583.0 pg/mg creatinine, 95% CI, 445.2-763.5) than exclusive cigarette smokers (130.6 ng/mL, 95% CI, 122.3-139.6 and 217.6 pg/mg creatinine, 95% CI, 193.0-245.2, respectively). Smokeless tobacco users also had higher concentrations of blood lead compared with nontobacco users (adjusted geometric mean ratio = 1.30, 95% CI, 1.21-1.38). Based on limited sample sizes, NNAL concentrations for smokeless tobacco users appear to have declined from 2007 to 2008 (geometric mean = 1013.7 pg/mg creatinine, 95% CI, 738.9-1390.8) to 2011 to 2012 (geometric mean = 325.7 pg/mg creatinine, 95% CI, 159.6-664.9).
Conclusions: Exclusive smokeless tobacco users have higher observed levels of exposure to nicotine and carcinogenic tobacco-specific nitrosamines, as measured by cotinine and NNAL biomarker concentrations, than exclusive cigarette smokers. These patterns in NNAL levels for smokeless tobacco users may be changing over time.
Impact: High exposure to harmful constituents among smokeless tobacco users is a continuing health issue. (C)2015 AACR.
C1 [Rostron, Brian L.; Chang, Cindy M.; van Bemmel, Dana M.] US FDA, Off Sci, Ctr Tobacco Prod, Silver Spring, MD 20993 USA.
[Xia, Yang; Blount, Benjamin C.] Ctr Dis Control & Prevent, Tobacco & Volatiles Branch, Div Sci Lab, Atlanta, GA USA.
RP Rostron, BL (reprint author), US FDA, 10903 New Hampshire Ave,Bldg 75,Room 4404, Silver Spring, MD 20993 USA.
EM brian.rostron@fda.hhs.gov
FU Intramural CDC HHS [CC999999]; NIEHS NIH HHS [R13 ES017566]
NR 34
TC 5
Z9 5
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD DEC
PY 2015
VL 24
IS 12
BP 1829
EP 1837
DI 10.1158/1055-9965.EPI-15-0376
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA CY0XB
UT WOS:000366129100003
PM 26582044
ER
PT J
AU Park, SY
Stultz, BG
Hursh, DA
AF Park, Sung Yeon
Stultz, Brian G.
Hursh, Deborah A.
TI Dual Role of Jun N-Terminal Kinase Activity in Bone Morphogenetic
Protein-Mediated Drosophila Ventral Head Development
SO GENETICS
LA English
DT Article
DE bone morphogenetic protein (BMP); decapentaplegic (dpp); Jun N-terminal
kinase (JNK); apoptosis; head morphogenesis; Drosophila
ID JNK SIGNALING PATHWAY; WING DISC EPITHELIA; IMAGINAL DISCS; CELL-DEATH;
ADULT HEAD; DECAPENTAPLEGIC EXPRESSION; GRADIENT FORMATION;
GENETIC-CONTROL; DORSAL CLOSURE; DPP
AB The Drosophila bone morphogenetic protein encoded by decapentaplegic (dpp) controls ventral head morphogenesis by expression in the head primordia, eye-antennal imaginal discs. These are epithelial sacs made of two layers: columnar disc proper cells and squamous cells of the peripodial epithelium. dpp expression related to head formation occurs in the peripodial epithelium; cisregulatory mutations disrupting this expression display defects in sensory vibrissae, rostral membrane, gena, and maxillary palps. Here we document that disruption of this dpp expression causes apoptosis in peripodial cells and underlying disc proper cells. We further show that peripodial Dpp acts directly on the disc proper, indicating that Dpp must cross the disc lumen to act. We demonstrate that palp defects are mechanistically separable from the other mutant phenotypes; both are affected by the c-Jun N-terminal kinase pathway but in opposite ways. Slight reduction of both Jun N-terminal kinase and Dpp activity in peripodial cells causes stronger vibrissae, rostral membrane, and gena defects than Dpp alone; additionally, strong reduction of Jun N-terminal kinase activity alone causes identical defects. A more severe reduction of dpp results in similar vibrissae, rostral membrane, and gena defects, but also causes mutant maxillary palps. This latter defect is correlated with increased peripodial Jun N-terminal kinase activity and can be caused solely by ectopic activation of Jun N-terminal kinase. We conclude that formation of sensory vibrissae, rostral membrane, and gena tissue in head morphogenesis requires the action of Jun N-terminal kinase in peripodial cells, while excessive Jun N-terminal kinase signaling in these same cells inhibits the formation of maxillary palps.
C1 [Park, Sung Yeon; Stultz, Brian G.; Hursh, Deborah A.] US FDA, Div Cell & Gene Therapies, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
[Park, Sung Yeon] Seoul Natl Univ, Biomed Sci Project BK21PLUS, Coll Med, Seoul 110799, South Korea.
RP Hursh, DA (reprint author), US FDA, Div Cell & Gene Therapies, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave,Bldg 72,Room 3216, Silver Spring, MD 20993 USA.
EM deborah.hursh@fda.hhs.gov
NR 70
TC 1
Z9 1
U1 0
U2 3
PU GENETICS SOCIETY AMERICA
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 0016-6731
EI 1943-2631
J9 GENETICS
JI Genetics
PD DEC
PY 2015
VL 201
IS 4
BP 1411
EP 1426
DI 10.1534/genetics.115.178376
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA CY4OC
UT WOS:000366386500011
PM 26500262
ER
PT J
AU Weaver, JD
Gutierrez, EJ
AF Weaver, Jason D.
Gutierrez, Erick J.
TI Comparing Rotary Bend Wire Fatigue Test Methods at Different Test Speeds
SO JOURNAL OF MATERIALS ENGINEERING AND PERFORMANCE
LA English
DT Article
DE biomaterial; test speed; wire fatigue
ID SHAPE-MEMORY ALLOY; NITINOL WIRE; FREQUENCY; DIAMETER; LIFE
AB Given its relatively simple setup and ability to produce results quickly, rotary bend fatigue testing is becoming commonplace in the medical device industry and is the subject of a new standard test method ASTM E2948-14. Although some research has been conducted to determine if results differ for different rotary bend fatigue test setups or test speeds, these parameters have not been extensively studied together. In this work, we investigate the effects of these two parameters on the fatigue life of three commonly used medical device alloys (ASTM F2063 nitinol, ASTM F138 stainless steel, and ASTM F1058 cobalt chromium). Results with three different rotary bend fatigue test setups revealed no difference in fatigue life among those setups. Increasing test speed, however, between 100 and 35,000 RPM led to an increased fatigue life for all three alloys studied (average number of cycles to fracture increased between 2.0 and 5.1 times between slowest and fastest test speed). Supplemental uniaxial tension tests of stainless steel wire at varying strain rates showed a strain rate dependence in the mechanical response which could in part explain the increased fatigue life at faster test speeds. How exactly strain rate dependence might affect the fatigue properties of different alloys at different alternating strain values requires further study. Given the difference in loading rates between benchtop fatigue tests and in vivo deformations, the potential for strain rate dependence should be considered when designing durability tests for medical devices and in extrapolating results of those tests to in vivo performance.
C1 [Weaver, Jason D.; Gutierrez, Erick J.] US FDA, Div Appl Mech, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA.
[Gutierrez, Erick J.] Oak Ridge Inst Sci & Educ, Oak Ridge, TN USA.
RP Weaver, JD (reprint author), US FDA, Div Appl Mech, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA.
EM jason.weaver@fda.hhs.gov
FU Division of Applied Mechanics, FDA's Medical Countermeasures Initiative;
U.S. Department of Energy; U.S. Food and Drug Administration
FX This project was supported by the Division of Applied Mechanics, FDA's
Medical Countermeasures Initiative, and an appointment to the Research
Participation Program at the Center for Devices and Radiological Health
administered by the Oak Ridge Institute for Science and Education
through an interagency agreement between the U.S. Department of Energy
and the U.S. Food and Drug Administration. The authors would like to
thank the following individuals for their thoughtful insights at various
stages of this project: Matthew Di Prima, Shiril Sivan, Terry Woods,
Kenneth L. Jerina, M. R. Mitchell, and L. D. Timmie Topoleski.
NR 23
TC 0
Z9 0
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1059-9495
EI 1544-1024
J9 J MATER ENG PERFORM
JI J. Mater. Eng. Perform.
PD DEC
PY 2015
VL 24
IS 12
BP 4966
EP 4974
DI 10.1007/s11665-015-1763-z
PG 9
WC Materials Science, Multidisciplinary
SC Materials Science
GA CY0PF
UT WOS:000366107300040
ER
PT J
AU Mocca, B
Yin, DD
Gao, YM
Wang, W
AF Mocca, Brian
Yin, Dandan
Gao, Yamei
Wang, Wei
TI Moraxella catarrhalis-produced nitric oxide has dual roles in
pathogenicity and clearance of infection in bacterial-host cell
co-cultures
SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY
LA English
DT Article
DE Nitrite reduction-derived nitric oxide; Infection; Apoptosis; Biofilms;
Bacterial pathogenesis; NO-induced cytokines and chemokines
ID TRUNCATED DENITRIFICATION PATHWAY; ENTERICA SEROVAR TYPHIMURIUM;
OUTER-MEMBRANE PROTEIN; ACUTE OTITIS-MEDIA; IN-VITRO;
NEISSERIA-MENINGITIDIS; SALMONELLA-ENTERICA; BIOFILM FORMATION; AIRWAY
INFLAMMATION; RESPIRATORY-TRACT
AB In humans, the free radical nitric oxide (NO center dot) is a concentration-dependent multifunctional signaling or toxic molecule that modulates various physiological and pathological processes, and innate immunity against bacterial infections. Because the expression of bacterial genes encoding nitrite reductase (AniA) and NO center dot reductase (NorB) is highly upregulated in biofilms in vitro, it is important to investigate whether bacterial NO center dot-metabolism might subvert host NO center dot signaling and play pathogenic roles during infection. The Moraxella catarrhalis AniA and NorB directly function in production and reduction of NO center dot. Using M. catarrhalis-human bronchial epithelial cell (HBEC) co-cultures, we recently reported AniA/nitrite-dependent cytotoxic effects on HBECs, including altered protein profiles of HBECs and induced HBEC apoptosis, suggesting bacterial nitrite reduction likely dysregulates host cell gene expression. To further clarify whether nitrite reduction-derived NO center dot or nitrite-dependent stimulation of bacterial growth was responsible for adverse effects on HBECs, we monitored bacterial nitrite reduction, levels of NO center dot in co-cultures and resulted dynamic effects on HBEC proliferation and bacterial viability. This study demonstrated that M. catarrhalis nitrite reduction-derived NO center dot was responsible for observed adverse effects on HBECs at mid-to-late stages of infection. More importantly, our data showed that while nitrite promoted bacterial growth and biofilm formation at early hours of infection, nitrite reduction-derived NO center dot was toxic towards M. catarrhalis in maturing biofilms, suggesting nitrite reduction-derived NO center dot might be a possible dualistic mechanism by which M. catarrhalis promotes diseases and spontaneous resolutions. Published by Elsevier Inc.
C1 [Mocca, Brian; Yin, Dandan; Wang, Wei] Food & Drug Adm, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
[Gao, Yamei] Food & Drug Adm, Div Viral Prod, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
RP Wang, W (reprint author), FDA CBER OVRR DBPAP, 10903 New Hampshire Ave,W075-G638,HFM428, Silver Spring, MD 20993 USA.
EM wei02.wang@fda.hhs.gov
FU FDA/CBER Operation Fund
FX This study was supported by the FDA/CBER Operation Fund to W. Wang. A
Research Participation Program administered by the Oak Ridge Institute
for Science and Education (ORISE, through an interagency agreement
between the U.S. Department of Energy and the U.S. FDA) provided support
to ORISE fellows. The authors thank Dieter C. Gruenert for providing
HBECs, Eric J. Hansen for providing M. catarrhalis O35E strains, Joaquin
Jaramillo Sabogal and Irene Yang (Summer Interns, administrated by
ORISE) for technical support, the FDA Nanotechnology Core Facility and
Dr. Jiwen Zheng for SEM instrument use and technical assistance.
NR 59
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U1 1
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1089-8603
EI 1089-8611
J9 NITRIC OXIDE-BIOL CH
JI Nitric Oxide-Biol. Chem.
PD DEC 1
PY 2015
VL 51
BP 52
EP 62
DI 10.1016/j.niox.2015.10.001
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CX9ZK
UT WOS:000366065100007
PM 26537639
ER
PT J
AU Plaut, RD
Stibitz, S
AF Plaut, Roger D.
Stibitz, Scott
TI Improvements to a Markerless Allelic Exchange System for Bacillus
anthracis
SO PLOS ONE
LA English
DT Article
ID YYCFG 2-COMPONENT SYSTEM; GRAM-POSITIVE BACTERIA; ESCHERICHIA-COLI; GENE
REPLACEMENT; LYTIC ENZYMES; STAPHYLOCOCCUS-AUREUS; BORDETELLA-PERTUSSIS;
ADENINE METHYLATION; SPORE GERMINATION; DNA
AB A system was previously developed for conducting I-SceI-mediated allelic exchange in Bacillus anthracis. In this system, recombinational loss of a chromosomally-integrated allelic exchange vector is stimulated by creation of a double-stranded break within the vector by the homing endonuclease I-SceI. Although this system is reasonably efficient and represents an improvement in the tools available for allelic exchange in B. anthracis, researchers are nonetheless required to "pick and patch" colonies in order to identify candidate "exchangeants." In the present study, a number of improvements have been made to this system: 1) an improved I-SceI-producing plasmid includes oriT so that both plasmids can now be introduced by conjugation, thus avoiding the need for preparing electro-competent cells of each integration intermediate; 2) antibiotic markers have been changed to allow the use of the system in select agent strains; and 3) both plasmids have been marked with fluorescent proteins, allowing the visualization of plasmid segregation on a plate and obviating the need for "picking and patching." These modifications have made the process easier, faster, and more efficient, allowing for parallel construction of larger numbers of mutant strains. Using this improved system, the genes encoding the tripartite anthrax toxin were deleted singly and in combination from plasmid pXO1 of Sterne strain 34F2. In the course of this study, we determined that DNA transfer to B. anthracis could be accomplished by conjugation directly from a methylation-competent E. coli strain.
C1 [Plaut, Roger D.; Stibitz, Scott] US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Silver Spring, MD 20993 USA.
RP Plaut, RD (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM Roger.Plaut@fda.hhs.gov
RI Plaut, Roger/B-2340-2013
OI Plaut, Roger/0000-0002-0883-972X
FU NIH/NIAID Middle Atlantic Regional Center of Excellence [U54 AI057168]
FX This work was supported by NIH/NIAID Middle Atlantic Regional Center of
Excellence grant U54 AI057168. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 39
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U1 2
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 1
PY 2015
VL 10
IS 12
AR e0142758
DI 10.1371/journal.pone.0142758
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CX7OL
UT WOS:000365891600010
PM 26624016
ER
PT J
AU Tovar, DA
Zhan, W
Rajan, SS
AF Tovar, David A.
Zhan, Wang
Rajan, Sunder S.
TI A Rotational Cylindrical fMRI Phantom for Image Quality Control
SO PLOS ONE
LA English
DT Article
ID RELAXATION-TIMES; FUNCTIONAL MRI; CORTEX; ASSURANCE; DYNAMICS; REVEALS;
DISEASE; TISSUE; BRAIN; TESLA
AB Purpose
A novel phantom for image quality testing for functional magnetic resonance imaging (fMRI) scans is described.
Methods
The cylindrical, rotatable, similar to 4.5L phantom, with eight wedge-shaped compartments, is used to simulate rest and activated states. The compartments contain NiCl2 doped agar gel with alternating concentrations of agar (1.4%, 1.6%) to produce T1 and T2 values approximating brain grey matter. The Jacard index was used to compare the image distortions for echo planar imaging (EPI) and gradient recalled echo (GRE) scans. Contrast to noise ratio ((CNR)) was compared across the imaging volume for GRE and EPI.
Results
The mean T2 for the two agar concentrations were found to be 106.5 +/- 4.8, 94.5 +/- 4.7 ms, and T1 of 1500 +/- 40 and 1485 +/- 30 ms, respectively. The Jacard index for GRE was generally found to be higher than for EPI (0.95 versus 0.8). The CNR varied from 20 to 50 across the slices and echo times used for EPI scans, and from 20 to 40 across the slices for the GRE scans. The phantom provided a reproducible CNR over 25 days.
Conclusions
The phantom provides a quantifiable signal change over a head-size imaging volume with EPI and GRE sequences, which was used for image quality assessment.
C1 [Tovar, David A.; Rajan, Sunder S.] US FDA, Div Biomed Phys, Silver Spring, MD 20993 USA.
[Zhan, Wang] Univ Maryland, Maryland Neuroimaging Ctr, College Pk, MD 20742 USA.
RP Rajan, SS (reprint author), US FDA, Div Biomed Phys, Silver Spring, MD 20993 USA.
EM Sunder.Rajan@fda.hhs.gov
NR 34
TC 1
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U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 1
PY 2015
VL 10
IS 12
AR e0143172
DI 10.1371/journal.pone.0143172
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CX7OL
UT WOS:000365891600017
PM 26625264
ER
PT J
AU Jimenez, AG
Suzuki, A
Stephens, C
Chen, M
Medina-Caliz, I
Robles-Diaz, M
Montane, E
Aldea, A
Andrade, RJ
Lucena, MI
AF Gonzalez Jimenez, A.
Suzuki, A.
Stephens, C.
Chen, M.
Medina-Caliz, I
Robles-Diaz, M.
Montane, E.
Aldea, A.
Andrade, R. J.
Lucena, M., I
TI THE INFLUENCE OF DRUG PHYSICOCHEMICAL PROPERTIES ON DELAYED ONSET IN
HEPATOTOXICITY: AN ANALYSIS OF THE COHORT INCLUDED IN THE SPANISH DILI
REGISTRY
SO BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
LA English
DT Meeting Abstract
C1 [Gonzalez Jimenez, A.; Stephens, C.; Robles-Diaz, M.; Montane, E.; Lucena, M., I] Univ Malaga, Hosp Virgen Victoria, IBIMA, E-29071 Malaga, Spain.
[Suzuki, A.] Univ Arkansas, Med Sci, Little Rock, AR 72204 USA.
[Chen, M.] CIBEReHD, Malaga, Spain.
[Medina-Caliz, I] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Aldea, A.] Hosp Germans Trias I Pujol, Badalona, Spain.
[Andrade, R. J.] Univ Hosp Canarias, Canarias, Spain.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1742-7835
EI 1742-7843
J9 BASIC CLIN PHARMACOL
JI Basic Clin. Pharmacol. Toxicol.
PD DEC
PY 2015
VL 117
SU 2
SI SI
MA C123
BP 40
EP 40
PG 1
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA CX5CD
UT WOS:000365717900126
ER
PT J
AU Omeir, R
Thomas, R
Teferedegne, B
Williams, C
Foseh, G
Macauley, J
Brinster, L
Beren, J
Peden, K
Breen, M
Lewis, AM
AF Omeir, R.
Thomas, R.
Teferedegne, B.
Williams, C.
Foseh, G.
Macauley, J.
Brinster, L.
Beren, J.
Peden, K.
Breen, M.
Lewis, A. M., Jr.
TI A novel canine kidney cell line model for the evaluation of neoplastic
development: karyotype evolution associated with spontaneous
immortalization and tumorigenicity
SO CHROMOSOME RESEARCH
LA English
DT Article
DE Neoplastic transformation; Tumorigenicity; Canine chromosomes;
Comparative genomic hybridization (CGH); Fluorescence in situ
hybridization (FISH); Madin-Darby canine kidney (MDCK) cell line;
CKB1-3T7 cell line
ID COPY NUMBER ABERRATIONS; CHINESE-HAMSTER CELLS; NEWBORN NUDE-MICE;
IN-VITRO; DOMESTIC DOG; CYTOGENETIC CHARACTERIZATION; DIFFERENTIATED
PROPERTIES; EMBRYO CELLS; ARRAY CGH; CHROMOSOME
AB The molecular mechanisms underlying spontaneous neoplastic transformation in cultured mammalian cells remain poorly understood, confounding recognition of parallels with the biology of naturally occurring cancer. The broad use of tumorigenic canine cell lines as research tools, coupled with the accumulation of cytogenomic data from naturally occurring canine cancers, makes the domestic dog an ideal system in which to investigate these relationships. We developed a canine kidney cell line, CKB1-3T7, which allows prospective examination of the onset of spontaneous immortalization and tumorigenicity. We documented the accumulation of cytogenomic aberrations in CKB1-3T7 over 24 months in continuous culture. The majority of aberrations emerged in parallel with key phenotypic changes in cell morphology, growth kinetics, and tumor incidence and latency. Focal deletion of CDKN2A/B emerged first, preceding the onset and progression of tumorigenic potential, and progressed to a homozygous deletion across the cell population during extended culture. Interestingly, CKB1-3T7 demonstrated a tumorigenic phenotype in vivo prior to exhibiting loss of contact inhibition in vitro. We also performed the first genome-wide characterization of the canine tumorigenic cell line MDCK, which also exhibited CDKN2A/B deletion. MDCK and CKB1-3T7 cells shared several additional aberrations that we have reported previously as being highly recurrent in spontaneous canine cancers, many of which, as with CDKN2A/B deletion, are evolutionarily conserved in their human counterparts. The conservation of these molecular events across multiple species, in vitro and in vivo, despite their contrasting karyotypic architecture, is a powerful indicator of a common mechanism underlying emerging neoplastic activity. Through integrated cytogenomic and phenotypic characterization of serial passages of CKB1-3T7 from initiation to development of a tumorigenic phenotype, we present a robust and readily accessible model (to be made available through the American Type Culture Collection) of spontaneous neoplastic transformation that overcomes many of the limitations of earlier studies.
C1 [Omeir, R.; Teferedegne, B.; Foseh, G.; Macauley, J.; Beren, J.; Lewis, A. M., Jr.] US FDA, Lab DNA Viruses, Div Viral Prod, Off Vaccines Res & Review,Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
[Thomas, R.; Williams, C.; Breen, M.] N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC 27607 USA.
[Thomas, R.; Breen, M.] N Carolina State Univ, Ctr Comparat Med & Translat Res, Raleigh, NC 27607 USA.
[Brinster, L.] NIH, Div Vet Resources, Bethesda, MD 20892 USA.
[Beren, J.] US FDA, Off Counter Terrorism & Emergency Coordinat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Breen, M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Canc Genet Program, Chapel Hill, NC 27599 USA.
[Breen, M.] N Carolina State Univ, Ctr Human Hlth & Environm, Raleigh, NC 27607 USA.
RP Lewis, AM (reprint author), US FDA, Lab DNA Viruses, Div Viral Prod, Off Vaccines Res & Review,Ctr Biol Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM matthew_breen@ncsu.edu; andrew.lewis@fda.hhs.gov
FU Division of Microbiology and Infectious Diseases of the National
Institute of Allergy and Infectious Diseases [YI-AI-4893-02NIAID];
Medical Counter Measures Initiative Grant; CBER Pandemic Influenza
Counter Measures Grant; NCSU Cancer Genomics Fund
FX This study was supported in part by a contract from the Division of
Microbiology and Infectious Diseases of the National Institute of
Allergy and Infectious Diseases through an Interagency Agreement with
CBER/FDA (contract number YI-AI-4893-02NIAID), Medical Counter Measures
Initiative Grant, and a CBER Pandemic Influenza Counter Measures Grant.
The molecular cytogenetics work was funded in part by the NCSU Cancer
Genomics Fund (MB). The CKB1-3T7 cell line was developed and its
biological properties characterized in LDNAV, CBER, FDA. Cytogenomic
evaluation of the CKB1-3T7 and MDCK cell lines was performed at North
Carolina State University. We thank Barry Falgout, Arifa Khan, Kari
Irvine, and Melissa Savage for critical review of the manuscript. All
authors contributed in the development of the manuscript for
publication.
NR 72
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U1 2
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0967-3849
EI 1573-6849
J9 CHROMOSOME RES
JI Chromosome Res.
PD DEC
PY 2015
VL 23
IS 4
BP 663
EP 680
DI 10.1007/s10577-015-9474-8
PG 18
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CX5OI
UT WOS:000365751100003
PM 25957863
ER
PT J
AU Nair, A
Lemery, SJ
Yang, J
Marathe, A
Zhao, L
Zhao, H
Jiang, XP
He, K
Ladouceur, G
Mitra, AK
Zhou, L
Fox, E
Aungst, S
Helms, W
Keegan, P
Pazdur, R
AF Nair, Abhilasha
Lemery, Steven J.
Yang, Jun
Marathe, Anshu
Zhao, Liang
Zhao, Hong
Jiang, Xiaoping
He, Kun
Ladouceur, Gaetan
Mitra, Amit K.
Zhou, Liang
Fox, Emily
Aungst, Stephanie
Helms, Whitney
Keegan, Patricia
Pazdur, Richard
TI FDA Approval Summary: Lenvatinib for Progressive,
Radio-iodine-Refractory Differentiated Thyroid Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CARCINOMA
AB The FDA approved lenvatinib (Lenvima, Eisai Inc.) for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory (RAI-refractory) differentiated thyroid cancer (DTC). In an international, multicenter, double-blinded, placebo-controlled trial (E7080-G000-303), 392 patients with locally recurrent or metastatic RAI-refractory DTC and radiographic evidence of disease progression within 12 months prior to randomization were randomly allocated (2: 1) to receive either lenvatinib 24 mg orally per day (n = 261) or matching placebo (n = 131) with the option for patients on the placebo arm to receive lenvatinib following independent radiologic confirmation of disease progression. A statistically significant prolongation of progression-free survival (PFS) as determined by independent radiology review was demonstrated [HR, 0.21; 95% confidence interval (CI), 0.16-0.28; P < 0.001, stratified log-rank test], with an estimated median PFS of 18.3 months (95% CI, 15.1, NR) in the lenvatinib arm and 3.6 months (95% CI, 2.2-3.7) in the placebo arm. The most common adverse reactions, in order of decreasing frequency, observed in the lenvatinib-treated patients were hypertension, fatigue, diarrhea, arthralgia/ myalgia, decreased appetite, decreased weight, nausea, stomatitis, headache, vomiting, proteinuria, palmar-plantar erythrodysesthesia syndrome, abdominal pain, and dysphonia. Adverse reactions led to dose reductions in 68% of patients receiving lenvatinib at the 24 mg dose and 18% of patients discontinued lenvatinib for adverse reactions leading to residual uncertainty regarding the optimal dose of lenvatinib. (C) 2015 AACR.
C1 [Nair, Abhilasha; Lemery, Steven J.; Fox, Emily; Aungst, Stephanie; Helms, Whitney; Keegan, Patricia; Pazdur, Richard] US FDA, Off Hematol & Oncol Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Yang, Jun; Marathe, Anshu; Zhao, Liang; Zhao, Hong] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Jiang, Xiaoping; He, Kun] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Ladouceur, Gaetan; Mitra, Amit K.; Zhou, Liang] US FDA, Off Pharmaceut Qual, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Nair, A (reprint author), US FDA, 10903 New Hampshire Ave,White Oak Bldg 22, Silver Spring, MD 20993 USA.
EM Abhilasha.Nair@fda.hhs.gov
NR 6
TC 6
Z9 6
U1 3
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD DEC 1
PY 2015
VL 21
IS 23
BP 5205
EP 5208
DI 10.1158/1078-0432.CCR-15-1377
PG 4
WC Oncology
SC Oncology
GA CX3MT
UT WOS:000365603800005
PM 26324740
ER
PT J
AU Yamazaki, M
Kim, MJ
Yu, C
Dwyer, K
Sobhan, M
Davis, D
Soule, L
Willett, G
AF Yamazaki, Michiyo
Kim, Myong-Jin
Yu, Chongwoo
Dwyer, Kate
Sobhan, Mahboob
Davis, Daniel
Soule, Lisa
Willett, Gerald
TI Effect of obesity on the effectiveness of hormonal contraceptives
Response
SO CONTRACEPTION
LA English
DT Letter
C1 [Yamazaki, Michiyo; Kim, Myong-Jin; Yu, Chongwoo] US FDA, Div Clin Pharmacol 3, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Dwyer, Kate; Sobhan, Mahboob] US FDA, Div Biostat 3, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Davis, Daniel; Soule, Lisa; Willett, Gerald] US FDA, Div Bone Reprod & Urol Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Yu, C (reprint author), US FDA, Div Clin Pharmacol 3, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
EM chongwoo.yu@fda.hhs.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0010-7824
EI 1879-0518
J9 CONTRACEPTION
JI Contraception
PD DEC
PY 2015
VL 92
IS 6
BP 602
EP 603
DI 10.1016/j.contraception.2015.09.017
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA CX2WC
UT WOS:000365556500017
PM 26585717
ER
PT J
AU Hulla, JE
Sahu, SC
Hayes, AW
AF Hulla, J. E.
Sahu, S. C.
Hayes, A. W.
TI Nanotechnology: History and future
SO HUMAN & EXPERIMENTAL TOXICOLOGY
LA English
DT Article
ID NANOSCALE MATERIALS; RESEARCH STRATEGIES; SAFETY EVALUATION;
NANOPARTICLES; NANOMATERIALS; DELIVERY; CANCER
C1 [Hulla, J. E.] US Army Corps Engn, Sacramento, CA USA.
[Sahu, S. C.] US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD USA.
[Hayes, A. W.] Harvard Univ, Cambridge, MA 02138 USA.
RP Hayes, AW (reprint author), Harvard Univ, Cambridge, MA 02138 USA.
EM awallacehayes@comcast.net
NR 30
TC 2
Z9 2
U1 10
U2 35
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0960-3271
EI 1477-0903
J9 HUM EXP TOXICOL
JI Hum. Exp. Toxicol.
PD DEC
PY 2015
VL 34
IS 12
BP 1318
EP 1321
DI 10.1177/0960327115603588
PG 4
WC Toxicology
SC Toxicology
GA CX5ME
UT WOS:000365745000017
PM 26614822
ER
PT J
AU Manirarora, JN
Wei, CH
AF Manirarora, Jean N.
Wei, Cheng-Hong
TI Combination Therapy Using IL-2/IL-2 Monoclonal Antibody Complexes,
Rapamycin, and Islet Autoantigen Peptides Increases Regulatory T Cell
Frequency and Protects against Spontaneous and Induced Type 1 Diabetes
in Nonobese Diabetic Mice
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID IN-VIVO; NOD MICE; AUTOIMMUNE-DISEASE; ANTIGEN; TOLERANCE; IL-2; VITRO;
IDENTIFICATION; SUPPRESSION; DESTRUCTION
AB Regulatory T cells (Treg) play a crucial role in the maintenance of self-tolerance. In this study, we sought to expand Ag-specific Tregs in vivo and investigate whether the expanded Tregs can prevent or delay the development of type 1 diabetes (T1D) in the NOD mouse model. NOD mice were treated with a combination of IL-2/anti-IL-2 Ab complex, islet Ag peptide, and rapamycin. After the combined treatment, CD4(+)CD25(+)Foxp3(+) Tregs were significantly expanded in vivo, they expressed classical Treg markers, exerted enhanced suppressive functions in vitro, and protected against spontaneous development of T1D in NOD mice. Moreover, treated mice were almost completely protected from the adoptively transferred, aggressive form of T1D caused by in vitro-activated cytotoxic islet Ag-specific CD8 T cells. Protection from T1D was transferrable by Tregs and could be attributed to reduced islet infiltration of immune cells as well as the skewing of the immune response toward a Th2 cytokine profile. This new method of peripheral immune regulation could potentially contribute to development of novel immunotherapeutic strategies to prevent the development of T1D or to promote tolerance to islet transplants without using immunosuppressive drugs for long terms.
C1 [Manirarora, Jean N.; Wei, Cheng-Hong] US FDA, Gene Transfer & Immunogen Branch, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies,Ctr Biol Eva, Silver Spring, MD 20993 USA.
RP Wei, CH (reprint author), US FDA, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave,Bldg 52-72,Room 3104, Silver Spring, MD 20993 USA.
EM chenghong_wei@yahoo.com
FU Food and Drug Administration Modernizing Science grant program; Division
of Cellular and Gene Therapies; Oak Ridge Institute for Science and
Education
FX This work was supported by the Food and Drug Administration Modernizing
Science grant program, as well as by the Division of Cellular and Gene
Therapies. J.N.M. was supported through a fellowship administered by the
Oak Ridge Institute for Science and Education.
NR 55
TC 2
Z9 2
U1 3
U2 8
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD DEC 1
PY 2015
VL 195
IS 11
BP 5203
EP 5214
DI 10.4049/jimmunol.1402540
PG 12
WC Immunology
SC Immunology
GA CX3NP
UT WOS:000365606100016
PM 26482409
ER
PT J
AU Thompson, A
Cattran, DC
Blank, M
Nachman, PH
AF Thompson, Aliza
Cattran, Daniel C.
Blank, Melanie
Nachman, Patrick H.
TI Complete and Partial Remission as Surrogate End Points in Membranous
Nephropathy
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID METHYLPREDNISOLONE PLUS CHLORAMBUCIL; RANDOMIZED CONTROLLED-TRIAL;
TUBULAR EPITHELIAL-CELLS; CHRONIC KIDNEY-DISEASE; NATURAL-HISTORY;
UNTREATED PATIENTS; NEPHROTIC SYNDROME; FOLLOW-UP; GLOMERULONEPHRITIS;
ALBUMIN
AB Absent a remission of proteinuria, primary membranous nephropathy (MN) can lead to ESRD over many years. Therefore, use of an earlier end point could facilitate the conduct of clinical trials. This manuscript evaluates complete remission (CR) and partial remission (PR) of proteinuria as surrogate end points for a treatment effect on ESRD in patients with primary MN with heavy proteinuria. CR is associated with a low relapse rate and excellent long-term renal survival, and it plausibly reflects remission of the disease process that leads to ESRD. Patients who achieve PR have better renal outcomes than those who do not but may have elevated relapse rates. How long PR must be maintained to yield a benefit on renal outcomes is also unknown. Hence, available data suggest that CR could be used as a surrogate end point in primary MN, whereas PR seems reasonably likely to predict clinical benefit. In the United States, surrogate end points that are reasonably likely to predict clinical benefit can be Used as a basis for accelerated approval; treatments approved under this program must verify the clinical benefit in postmarketing trials. Additional analyses of the relationship between treatment effects on CR and PR and subsequent renal outcomes would inform the design of future clinical trials in primary MN.
C1 [Thompson, Aliza; Blank, Melanie] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Cattran, Daniel C.] Toronto Gen Hosp, Toronto Gen Res Inst, Div Clin Invest & Human Physiol, Toronto, ON, Canada.
[Nachman, Patrick H.] Univ N Carolina, Univ North Carolina Kidney Ctr, Chapel Hill, NC 27599 USA.
RP Nachman, PH (reprint author), Univ N Carolina, Univ North Carolina Kidney Ctr, CB 7155,7004 Burnett Womack Bldg, Chapel Hill, NC 27599 USA.
EM patrick_nachman@med.unc.edu
FU American Society of Nephrology Glomerular Disease Advisory Group
FX The authors acknowledge the support of the American Society of
Nephrology Glomerular Disease Advisory Group.
NR 41
TC 7
Z9 7
U1 1
U2 5
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD DEC
PY 2015
VL 26
IS 12
BP 2930
EP 2937
DI 10.1681/ASN.2015010091
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA CX1OR
UT WOS:000365466000008
PM 26078365
ER
PT J
AU Menachery, VD
Yount, BL
Debbink, K
Agnihothram, S
Gralinski, LE
Plante, JA
Graham, RL
Scobey, T
Ge, XY
Donaldson, EF
Randell, SH
Lanzavecchia, A
Marasco, WA
Shi, ZLL
Baric, RS
AF Menachery, Vineet D.
Yount, Boyd L., Jr.
Debbink, Kari
Agnihothram, Sudhakar
Gralinski, Lisa E.
Plante, Jessica A.
Graham, Rachel L.
Scobey, Trevor
Ge, Xing-Yi
Donaldson, Eric F.
Randell, Scott H.
Lanzavecchia, Antonio
Marasco, Wayne A.
Shi, Zhengli-Li
Baric, Ralph S.
TI A SARS-like cluster of circulating bat coronaviruses shows potential for
human emergence
SO NATURE MEDICINE
LA English
DT Article
ID ACUTE RESPIRATORY SYNDROME; RECEPTOR; DISEASE; CELLS; INFECTIONS;
MECHANISMS; FITNESS; VACCINE; ESCAPE; MICE
AB The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations(1). Using the SARS-CoV reverse genetics system(2), we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein. On the basis of these findings, we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Our work suggests a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations.
C1 [Menachery, Vineet D.; Yount, Boyd L., Jr.; Debbink, Kari; Gralinski, Lisa E.; Plante, Jessica A.; Graham, Rachel L.; Scobey, Trevor; Donaldson, Eric F.; Baric, Ralph S.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA.
[Baric, Ralph S.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA.
[Agnihothram, Sudhakar] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Ge, Xing-Yi; Shi, Zhengli-Li] Chinese Acad Sci, Wuhan Inst Virol, Key Lab Special Pathogens & Biosafety, Wuhan, Peoples R China.
[Randell, Scott H.] Univ N Carolina, Dept Cell Biol & Physiol, Chapel Hill, NC USA.
[Randell, Scott H.] Univ N Carolina, Cyst Fibrosis Ctr, Marsico Lung Inst, Chapel Hill, NC USA.
[Lanzavecchia, Antonio] Bellinzona Inst Microbiol, Inst Res Biomed, Zurich, Switzerland.
[Marasco, Wayne A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Marasco, Wayne A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Baric, RS (reprint author), Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA.
EM vineet@email.unc.edu
FU National Institute of Allergy & Infectious Disease; National Institute
of Aging of the US National Institutes of Health (NIH) [U19AI109761,
U19AI107810, AI085524, F32AI102561, K99AG049092]; National Natural
Science Foundation of China [81290341, 31470260]; USAID-EPT-PREDICT from
EcoHealth Alliance; National Institute of Diabetes and Digestive and
Kidney Disease of the NIH [NIH DK065988]
FX Research in this manuscript was supported by grants from the National
Institute of Allergy & Infectious Disease and the National Institute of
Aging of the US National Institutes of Health (NIH) under awards
U19AI109761 (R.S.B.), U19AI107810 (R.S.B.), AI085524 (W.A.M.),
F32AI102561 (V.D.M.) and K99AG049092 (V.D.M.), and by the National
Natural Science Foundation of China awards 81290341 (Z.-L.S.) and
31470260 (X.-Y.G.), and by USAID-EPT-PREDICT funding from EcoHealth
Alliance (Z.-L.S.). Human airway epithelial cultures were supported by
the National Institute of Diabetes and Digestive and Kidney Disease of
the NIH under award NIH DK065988 (S.H.R.). We also thank M.T. Ferris
(Dept. of Genetics, University of North Carolina) for the reviewing of
statistical approaches and C.T. Tseng (Dept. of Microbiology and
Immunology, University of Texas Medical Branch) for providing Calu-3
cells. Experiments with the full-length and chimeric SHC014 recombinant
viruses were initiated and performed before the GOF research funding
pause and have since been reviewed and approved for continued study by
the NIH. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the NIH.
NR 27
TC 27
Z9 28
U1 4
U2 25
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD DEC
PY 2015
VL 21
IS 12
BP 1508
EP +
DI 10.1038/nm.3985
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA CX9EV
UT WOS:000366008700023
PM 26552008
ER
PT J
AU Mullard, A
Midthun, K
AF Mullard, Asher
Midthun, Karen
TI Karen Midthun
SO NATURE REVIEWS DRUG DISCOVERY
LA English
DT Editorial Material
C1 [Midthun, Karen] CBER, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1776
EI 1474-1784
J9 NAT REV DRUG DISCOV
JI Nat. Rev. Drug Discov.
PD DEC
PY 2015
VL 14
IS 12
BP 814
EP 814
DI 10.1038/nrd4792
PG 1
WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
GA CX6FD
UT WOS:000365795700009
ER
PT J
AU Li, F
Chu, HT
Nie, L
AF Li, Feng
Chu, Haitao
Nie, Lei
TI A two-stage estimation for screening studies using two diagnostic tests
with binary disease status verified in test positives only
SO STATISTICAL METHODS IN MEDICAL RESEARCH
LA English
DT Article
DE dependence; diagnostic test accuracy; homogeneous association; screening
studies
ID CAPTURE-RECAPTURE APPROACH; LATENT CLASS ANALYSIS; GOLD STANDARD;
INTRACLASS CORRELATION; CLASS MODELS; ACCURACY; AVAILABILITY;
COEFFICIENT; SPECIFICITY; SENSITIVITY
AB This article considers the statistical estimation and inference for screening studies in which two binary tests are used for screening with a binary disease status verified only for those subjects with at least one positive test result. The challenge encountered in these studies is the non-identifiability because the disease rate is not identifiable for subjects with negative results from both tests without additional assumptions. Different homogeneous association models have been proposed in the literature to circumvent the non-identifiability problem, which were solved using numerical methods. We propose to formulate the problem as a constrained maximum likelihood estimation (MLE) problem. The MLE has a closed-form in general, which can be solved using a unified two-stage estimation approach. We demonstrate the application of the proposed method on a set of homogeneous association models. The homogeneous association assumptions are generally not testable as all models are saturated. Therefore, we propose an association-ratio plot as a visualization tool for model comparisons. The methods are illustrated through three examples.
C1 [Li, Feng] US FDA, Div Biometr 2, Off Biostat, Silver Spring, MD 20993 USA.
[Chu, Haitao] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA.
[Nie, Lei] US FDA, Div Biometr 4, Off Biostat, Silver Spring, MD 20993 USA.
RP Nie, L (reprint author), US FDA, Div Biometr 4, Off Biostat, Silver Spring, MD 20993 USA.
EM lei.nie@fda.hhs.gov
NR 32
TC 0
Z9 0
U1 2
U2 6
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0962-2802
EI 1477-0334
J9 STAT METHODS MED RES
JI Stat. Methods Med. Res.
PD DEC
PY 2015
VL 24
IS 6
BP 635
EP 656
DI 10.1177/0962280211421838
PG 22
WC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Statistics & Probability
SC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Mathematics
GA CX5AG
UT WOS:000365712000002
PM 21920876
ER
PT J
AU Chen, Y
Chu, HT
Luo, S
Nie, L
Chen, SN
AF Chen, Yong
Chu, Haitao
Luo, Sheng
Nie, Lei
Chen, Sining
TI Bayesian analysis on meta-analysis of case-control studies accounting
for within-study correlation
SO STATISTICAL METHODS IN MEDICAL RESEARCH
LA English
DT Article
DE bivariate beta-binomial model; exact method; hypergeometric function;
meta-analysis; odds ratio; Sarmanov family
ID SAMPLE CONFIDENCE-INTERVALS; EMPIRICAL BAYES; COLORECTAL-CANCER; SPARSE
DATA; ODDS RATIO; PROPORTIONS; MODEL; DISTRIBUTIONS; PERFORMANCE;
INFERENCE
AB In retrospective studies, odds ratio is often used as the measure of association. Under independent beta prior assumption, the exact posterior distribution of odds ratio given a single 2x2 table has been derived in the literature. However, independence between risks within the same study may be an oversimplified assumption because cases and controls in the same study are likely to share some common factors and thus to be correlated. Furthermore, in a meta-analysis of case-control studies, investigators usually have multiple 2x2 tables. In this article, we first extend the published results on a single 2x2 table to allow within study prior correlation while retaining the advantage of closed-form posterior formula, and then extend the results to multiple 2x2 tables and regression setting. The hyperparameters, including within study correlation, are estimated via an empirical Bayes approach. The overall odds ratio and the exact posterior distribution of the study-specific odds ratio are inferred based on the estimated hyperparameters. We conduct simulation studies to verify our exact posterior distribution formulas and investigate the finite sample properties of the inference for the overall odds ratio. The results are illustrated through a twin study for genetic heritability and a meta-analysis for the association between the N-acetyltransferase 2 (NAT2) acetylation status and colorectal cancer.
C1 [Chen, Yong; Luo, Sheng] Univ Texas Hlth Sci Ctr Houston, Div Biostat, Houston, TX 77030 USA.
[Chu, Haitao] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA.
[Nie, Lei] OTS CDER FDA, Off Biostat, Div 4, Spring, MD USA.
[Chen, Sining] Bell Labs, Dept Stat & Learning, Murray Hill, NJ 07974 USA.
RP Chen, Y (reprint author), Univ Texas Hlth Sci Ctr Houston, Div Biostat, 1200 Herman Pressler, Houston, TX 77030 USA.
EM yong.chen@uth.tmc.edu
FU University of Texas School of Public Health; US Department of Health and
Human Services Agency for Healthcare Research and Quality from the U.S.
National Cancer Institute [R03HS020666, P01CA142538]; NIH/NINDS [U01
NS043127, U01 NS43128]
FX Views expressed in this paper are the author's professional opinions and
do not necessarily represent the official positions of the US Food and
Drug Administration. Yong Chen's research was partially supported by a
start-up fund from the University of Texas School of Public Health.
Haitao Chu was supported in part by the US Department of Health and
Human Services Agency for Healthcare Research and Quality Grant
R03HS020666 and P01CA142538 from the U.S. National Cancer Institute.
Sheng Luo's research was partially supported by two NIH/NINDS grants:
U01 NS043127 and U01 NS43128. We gratefully acknowledge the editor, Dr.
Brian Everitt, and an anonymous reviewer for constructive comments that
greatly improved the manuscript. We also want to thank Peng Wei for the
helpful comments.
NR 51
TC 2
Z9 2
U1 0
U2 3
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0962-2802
EI 1477-0334
J9 STAT METHODS MED RES
JI Stat. Methods Med. Res.
PD DEC
PY 2015
VL 24
IS 6
BP 836
EP 855
DI 10.1177/0962280211430889
PG 20
WC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Statistics & Probability
SC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Mathematics
GA CX5AG
UT WOS:000365712000013
PM 22143403
ER
PT J
AU Avonto, C
Chittiboyina, AG
Rua, D
Khan, IA
AF Avonto, Cristina
Chittiboyina, Amar G.
Rua, Diego
Khan, Ikhlas A.
TI A fluorescence high throughput screening method for the detection of
reactive electrophiles as potential skin sensitizers
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Skin sensitization; Electrophiles; In chemico alternative methods;
Fluorescence assay; High throughput screening
ID ALLERGIC CONTACT-DERMATITIS; SESQUITERPENE LACTONE MIX; TEST H-CLAT;
PEPTIDE REACTIVITY; IN-VITRO; CELL-LINE; MICHAEL ACCEPTORS; GUINEA PIG;
POTENCY; ASSAY
AB Skin sensitization is an important toxicological end-point in the risk assessment of chemical allergens. Because of the complexity of the biological mechanisms associated with skin sensitization, integrated approaches combining different chemical, biological and in silico methods are recommended to replace conventional animal tests. Chemical methods are intended to characterize the potential of a sensitizer to induce earlier molecular initiating events. The presence of an electrophilic mechanistic domain is considered one of the essential chemical features to covalently bind to the biological target and induce further haptenation processes. Current in chemico assays rely on the quantification of unreacted model nucleophiles after incubation with the candidate sensitizer. In the current study, a new fluorescence-based method, 'HTS-DCYA assay', is proposed. The assay aims at the identification of reactive electrophiles based on their chemical reactivity toward a model fluorescent thiol. The reaction workflow enabled the development of a High Throughput Screening (HTS) method to directly quantify the reaction adducts. The reaction conditions have been optimized to minimize solubility issues, oxidative side reactions and increase the throughput of the assay while minimizing the reaction time, which are common issues with existing methods. Thirty-six chemicals previously classified with LLNA, DPRA or KeratinoSens (TM) were tested as a proof of concept. Preliminary results gave an estimated 82% accuracy, 78% sensitivity, 90% specificity, comparable to other in chemico methods such as Cys-DPRA. In addition to validated chemicals, six natural products were analyzed and a prediction of their sensitization potential is presented for the first rime. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Avonto, Cristina; Chittiboyina, Amar G.; Khan, Ikhlas A.] Univ Mississippi, Natl Ctr Nat Prod Res, Pharmaceut Sci Res Inst, Sch Pharm, University, MS 38677 USA.
[Rua, Diego] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Khan, Ikhlas A.] Univ Mississippi, Div Pharmacognosy, Dept Biomol Sci, Sch Pharm, University, MS 38677 USA.
RP Khan, IA (reprint author), Univ Mississippi, Natl Ctr Nat Prod Res, University, MS 38677 USA.
EM ikhan@olemiss.edu
OI Avonto, Cristina/0000-0002-8209-6813
FU Food and Drug Administration [1U01FD004246-04]; U.S. Department of
Agriculture, Agricultural Research Service [58-6408-1-603-04]
FX This work was supported in part by the Food and Drug Administration
[grant number 1U01FD004246-04] and the U.S. Department of Agriculture,
Agricultural Research Service, [Specific Cooperative Agreement No.
58-6408-1-603-04].
NR 49
TC 5
Z9 5
U1 0
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
EI 1096-0333
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD DEC 1
PY 2015
VL 289
IS 2
BP 177
EP 184
DI 10.1016/j.taap.2015.09.027
PG 8
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA CX1NC
UT WOS:000365461900005
PM 26455772
ER
PT J
AU Walters, JL
Lansdell, TA
Lookingland, KJ
Baker, LE
AF Walters, Jennifer L.
Lansdell, Theresa A.
Lookingland, Keith J.
Baker, Lisa E.
TI The effects of gestational and chronic atrazine exposure on motor
behaviors and striatal dopamine in male Sprague-Dawley rats
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Atrazine; Dopamine; Striatum; Locomotor activity; Motor function;
Behavior
ID MALE C57BL/6 MICE; HERBICIDE ATRAZINE; PARKINSONS-DISEASE;
LOCOMOTOR-ACTIVITY; PREFRONTAL CORTEX; FEMALE RATS; TOXICITY; REVERSAL;
LESIONS; METABOLITES
AB This study sought to investigate the effects of environmentally relevant gestational followed by continued chronic exposure to the herbicide, atrazine, on motor function, cognition, and neurochemical indices of nigrostriatal dopamine (DA) activity in male rats. Dams were treated with 100 mu g/kg atrazine, 10 mg/kg atrazine, or vehicle on gestational day 1 through postnatal day 21. Upon weaning, male offspring continued daily vehicle or atrazine gavage treatments for an additional six months. Subjects were tested in a series of behavioral assays, and 24 h after the last treatment, tissue samples from the striatum were analyzed for DA and 3,4-dihydroxyphenylacetic acid (DOPAC). At 10 mg/kg, this herbicide was found to produce modest disruptions in motor functioning, and at both dose levels it significantly lowered striatal DA and DOPAC concentrations. These results suggest that exposures to atrazine have the potential to disrupt nigrostriatal DA neurons and behaviors associated with motor functioning. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Walters, Jennifer L.; Baker, Lisa E.] Western Michigan Univ, Dept Psychol, Kalamazoo, MI 49008 USA.
[Lansdell, Theresa A.; Lookingland, Keith J.] Michigan State Univ, Dept Pharmacol & Toxicol, E Lansing, MI 48824 USA.
RP Walters, JL (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM Jennifer.l.walters@wmich.edu; lansdel1@msu.edu; lookingl@msu.edu;
lisa.baker@wmich.edu
FU NIGMS NIH HHS [T32 GM092715]
NR 67
TC 1
Z9 1
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
EI 1096-0333
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD DEC 1
PY 2015
VL 289
IS 2
BP 185
EP 192
DI 10.1016/j.taap.2015.09.026
PG 8
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA CX1NC
UT WOS:000365461900006
PM 26440580
ER
PT J
AU Chen, RT
Shimabukuro, TT
Martin, DB
Zuber, PLF
Weibel, DM
Sturkenboom, M
AF Chen, Robert T.
Shimabukuro, Tom T.
Martin, David B.
Zuber, Patrick L. F.
Weibel, Daniel M.
Sturkenboom, Miriam
TI Enhancing Vaccine Safety Capacity Globally A Lifecycle Perspective
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID GUILLAIN-BARRE-SYNDROME; REPORTING-SYSTEM VAERS; INACTIVATED POLIOVIRUS
VACCINATION; EVENTS FOLLOWING IMMUNIZATION; MUMPS-RUBELLA VACCINE;
UNITED-STATES; ADVERSE EVENTS; INFLUENZA VACCINE; DATALINK PROJECT;
ADVISORY-COMMITTEE
AB Major vaccine safety controversies have arisen in several countries beginning in the last decades of 20th century. Such periodic vaccine safety controversies are unlikely to go away in the near future as more national immunization programs mature with near elimination of target vaccine-preventable diseases that result in relative greater prominence of adverse events following immunizations, both true reactions and temporally coincidental events. There are several ways in which vaccine safety capacity can be improved to potentially mitigate the impact of future vaccine safety controversies. This paper aims to take a "lifecyde" approach, examining some potential pre- and post-licensure opportunities to improve vaccine safety, in both developed (specifically U.S. and Europe) and low- and middle-income countries. (C) 2015 by American Journal of Preventive Medicine and Elsevier Ltd. All rights reserved.
C1 [Chen, Robert T.; Shimabukuro, Tom T.] Ctr Dis Control & Prevent, Off Infect Dis, Atlanta, GA USA.
[Martin, David B.] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
[Zuber, Patrick L. F.] WHO, CH-1211 Geneva, Switzerland.
[Weibel, Daniel M.; Sturkenboom, Miriam] Erasmus Univ, Med Ctr, Rotterdam, Netherlands.
RP Chen, RT (reprint author), 1600 Clifton Rd MS-E45, Atlanta, GA 30333 USA.
EM bchen@cdc.gov
FU Merck; Novartis
FX This article is being published concurrently in the American Journal of
Preventive Medicine and Vaccine. The articles are identical except for
stylistic changes in keeping with each journal's style. Either of these
versions may be used in citing this article. Publication of this article
was supported by Merck and Novartis.
NR 155
TC 2
Z9 2
U1 0
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD DEC
PY 2015
VL 49
IS 6
SU 4
BP S364
EP S376
DI 10.1016/j.amepre.2015.09.009
PG 13
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA CW5UI
UT WOS:000365061700007
PM 26590436
ER
PT J
AU Lerner, DL
Pezeshk, A
AF Lerner, David L.
Pezeshk, Aria
TI The Use of Lossy Compression of Digital Mammograms for Primary
Interpretation and Image Retention
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Letter
ID NONINFERIORITY; SIMILARITY; ROC
C1 [Lerner, David L.] US FDA, Ctr Devices & Radiol Hlth, Off Vitro Diagnost & Radiol Hlth, Silver Spring, MD 20993 USA.
[Pezeshk, Aria] US FDA, Ctr Devices & Radiol Hlth, OSEL Div Imaging Diagnost & Software Reliabil, Silver Spring, MD USA.
RP Lerner, DL (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Vitro Diagnost & Radiol Hlth, Silver Spring, MD 20993 USA.
EM david.lerner@fda.hhs.gov
NR 10
TC 1
Z9 1
U1 0
U2 1
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
EI 1546-3141
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD DEC
PY 2015
VL 205
IS 6
BP W640
EP W641
DI 10.2214/AJR.15.15130
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CW9LO
UT WOS:000365320400010
PM 26587954
ER
PT J
AU Li, BG
Jackson, SA
Gangiredla, J
Wang, WM
Liu, HL
Tall, BD
Beaubrun, JJG
Jay-Russell, M
Vellidis, G
Elkins, CA
AF Li, Baoguang
Jackson, Scott A.
Gangiredla, Jayanthi
Wang, Weimin
Liu, Huanli
Tall, Ben D.
Beaubrun, Junia Jean-Gilles
Jay-Russell, Michele
Vellidis, George
Elkins, Christopher A.
TI Genomic Evidence Reveals Numerous Salmonella enterica Serovar Newport
Reintroduction Events in Suwannee Watershed Irrigation Ponds
SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY
LA English
DT Article
ID SOUTHEASTERN UNITED-STATES; GEL-ELECTROPHORESIS; FRESH PRODUCE;
PERSISTENCE; SURVIVAL; ENTERITIDIS; ENVIRONMENTS; TYPHIMURIUM;
RESISTANCE; DIVERSITY
AB Our previous work indicated a predominance (56.8%) of Salmonella enterica serovar Newport among isolates recovered from irrigation ponds used in produce farms over a 2-year period (B. Li et al., Appl Environ Microbiol 80: 6355-6365, http://dx.doi.org/10.1128/AEM.02063-14). This observation provided a valuable set of metrics to explore an underaddressed issue of environmental survival of Salmonella by DNA microarray. Microarray analysis correctly identified all the isolates (n = 53) and differentiated the S. Newport isolates into two phylogenetic lineages (S. Newport II and S. Newport III). Serovar distribution analysis showed no instances where the same serovar was recovered from a pond for more than a month. Furthermore, during the study, numerous isolates with an indistinguishable genotype were recovered from different ponds as far as 180 km apart for time intervals as long as 2 years. Although isolates within either lineage were phylogenetically related as determined by microarray analysis, subtle genotypic differences were detected within the lineages, suggesting that isolates in either lineage could have come from several unique hosts. For example, strains in four different subgroups (A, B, C, and D) possessed an indistinguishable genotype within their subgroups as measured by gene differences, suggesting that strains in each subgroup shared a common host. Based on this comparative genomic evidence and the spatial and temporal factors, we speculated that the presence of Salmonella in the ponds was likely due to numerous punctuated reintroduction events associated with several different but common hosts in the environment. These findings may have implications for the development of strategies for efficient and safe irrigation to minimize the risk of Salmonella outbreaks associated with fresh produce.
C1 [Li, Baoguang; Jackson, Scott A.; Gangiredla, Jayanthi; Wang, Weimin; Liu, Huanli; Elkins, Christopher A.] US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, Laurel, MD 20707 USA.
[Tall, Ben D.; Beaubrun, Junia Jean-Gilles] US FDA, Div Virulence Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD USA.
[Jay-Russell, Michele] Univ Calif Davis, Western Ctr Food Safety, Davis, CA 95616 USA.
[Vellidis, George] Univ Georgia, Tifton, GA USA.
RP Li, BG (reprint author), US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, Laurel, MD 20707 USA.
EM baoguang.li@fda.hhs.gov
OI Tall, Ben/0000-0003-0399-3629
NR 46
TC 2
Z9 2
U1 1
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0099-2240
EI 1098-5336
J9 APPL ENVIRON MICROB
JI Appl. Environ. Microbiol.
PD DEC
PY 2015
VL 81
IS 24
BP 8243
EP 8253
DI 10.1128/AEM.02179-15
PG 11
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA CW7XN
UT WOS:000365212800001
PM 26386063
ER
PT J
AU Ajao, A
Nystrom, SV
Koonin, LM
Patel, A
Howell, DR
Baccam, P
Lant, T
Malatino, E
Chamberlin, M
Meltzer, MI
AF Ajao, Adebola
Nystrom, Scott V.
Koonin, Lisa M.
Patel, Anita
Howell, David R.
Baccam, Prasith
Lant, Tim
Malatino, Eileen
Chamberlin, Margaret
Meltzer, Martin I.
TI Assessing the Capacity of the US Health Care System to Use Additional
Mechanical Ventilators During a Large-Scale Public Health Emergency
SO DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS
LA English
DT Article
DE pandemic; public health emergency; surge capacity; mechanical
ventilators; model
ID MASS CRITICAL-CARE; SURGE CAPACITY; DEFINITIVE CARE; CRITICALLY-ILL;
UNITED-STATES; JANUARY 26-27; TASK-FORCE; OCCUPANCY; HOSPITALS; DISASTER
AB Objective A large-scale public health emergency, such as a severe influenza pandemic, can generate large numbers of critically ill patients in a short time. We modeled the number of mechanical ventilators that could be used in addition to the number of hospital-based ventilators currently in use.
Methods We identified key components of the health care system needed to deliver ventilation therapy, quantified the maximum number of additional ventilators that each key component could support at various capacity levels (ie, conventional, contingency, and crisis), and determined the constraining key component at each capacity level.
Results Our study results showed that US hospitals could absorb between 26,200 and 56,300 additional ventilators at the peak of a national influenza pandemic outbreak with robust pre-pandemic planning.
Conclusions The current US health care system may have limited capacity to use additional mechanical ventilators during a large-scale public health emergency. Emergency planners need to understand their health care systems' capability to absorb additional resources and expand care. This methodology could be adapted by emergency planners to determine stockpiling goals for critical resources or to identify alternatives to manage overwhelming critical care need. (Disaster Med Public Health Preparedness. 2015;9:634-641)
C1 [Ajao, Adebola] US FDA, Silver Spring, MD 20993 USA.
[Nystrom, Scott V.; Howell, David R.; Lant, Tim] US Dept HHS, Washington, DC 20201 USA.
[Koonin, Lisa M.; Patel, Anita; Malatino, Eileen; Meltzer, Martin I.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Baccam, Prasith] IEM Inc, Morrisville, NC USA.
[Chamberlin, Margaret] Pardee Rand Grad Sch, Santa Monica, CA USA.
RP Ajao, A (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM adebola.ajao@fda.hhs.gov
FU Intramural CDC HHS [CC999999]
NR 23
TC 2
Z9 3
U1 1
U2 4
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1935-7893
EI 1938-744X
J9 DISASTER MED PUBLIC
JI Dis. Med. Public Health Prep.
PD DEC
PY 2015
VL 9
IS 6
BP 634
EP 641
DI 10.1017/dmp.2015.105
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CW9MP
UT WOS:000365323100008
PM 26450633
ER
PT J
AU Abanyie, F
Harvey, RR
Harris, JR
Wiegand, RE
Gaul, L
Desvignes-Kendrick, M
Irvin, K
Williams, I
Hall, RL
Herwaldt, B
Gray, EB
Qvarnstrom, Y
Wise, ME
Cantu, V
Cantey, PT
Bosch, S
Da Silva, AJ
Fields, A
Bishop, H
Wellman, A
Beal, J
Wilson, N
Fiore, AE
Tauxe, R
Lance, S
Slutsker, L
Parise, M
AF Abanyie, F.
Harvey, R. R.
Harris, J. R.
Wiegand, R. E.
Gaul, L.
Desvignes-Kendrick, M.
Irvin, K.
Williams, I.
Hall, R. L.
Herwaldt, B.
Gray, E. B.
Qvarnstrom, Y.
Wise, M. E.
Cantu, V.
Cantey, P. T.
Bosch, S.
Da Silva, A. J.
Fields, A.
Bishop, H.
Wellman, A.
Beal, J.
Wilson, N.
Fiore, A. E.
Tauxe, R.
Lance, S.
Slutsker, L.
Parise, M.
CA Multistate Cyclosporiasis Outbreak
TI 2013 multistate outbreaks of Cyclospora cayetanensis infections
associated with fresh produce: focus on the Texas investigations
SO EPIDEMIOLOGY AND INFECTION
LA English
DT Article
DE Cyclospora; outbreaks; parasites
ID IMPORTED RASPBERRIES; CANADA
AB The 2013 multistate outbreaks contributed to the largest annual number of reported US cases of cyclosporiasis since 1997. In this paper we focus on investigations in Texas. We defined an outbreak-associated case as laboratory-confirmed cyclosporiasis in a person with illness onset between 1 June and 31 August 2013, with no history of international travel in the previous 14 days. Epidemiological, environmental, and traceback investigations were conducted. Of the 631 cases reported in the multistate outbreaks, Texas reported the greatest number of cases, 270 (43%). More than 70 clusters were identified in Texas, four of which were further investigated. One restaurant-associated cluster of 25 case-patients was selected for a case-control study. Consumption of cilantro was most strongly associated with illness on meal date-matched analysis (matched odds ratio 19.8, 95% confidence interval 4.0-infinity). All case-patients in the other three clusters investigated also ate cilantro. Traceback investigations converged on three suppliers in Puebla, Mexico. Cilantro was the vehicle of infection in the four clusters investigated; the temporal association of these clusters with the large overall increase in cyclosporiasis cases in Texas suggests cilantro was the vehicle of infection for many other cases. However, the paucity of epidemiological and traceback information does not allow for a conclusive determination; moreover, molecular epidemiological tools for cyclosporiasis that could provide more definitive linkage between case clusters are needed.
C1 [Abanyie, F.; Harris, J. R.; Wiegand, R. E.; Hall, R. L.; Herwaldt, B.; Gray, E. B.; Qvarnstrom, Y.; Cantey, P. T.; Da Silva, A. J.; Bishop, H.; Wilson, N.; Fiore, A. E.; Slutsker, L.; Parise, M.] Ctr Dis Control & Prevent, Ctr Global Hlth, Div Parasit Dis & Malaria, Atlanta, GA 30333 USA.
[Harvey, R. R.; Wilson, N.] Ctr Dis Control & Prevent, Epidem Intelligence Serv, Atlanta, GA 30333 USA.
[Harvey, R. R.; Williams, I.; Wise, M. E.; Bosch, S.; Tauxe, R.; Lance, S.] Ctr Dis Control & Prevent, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA.
[Gaul, L.; Cantu, V.] Texas Dept State Hlth Serv, Austin, TX USA.
[Desvignes-Kendrick, M.] Ft Bend Cty Hlth & Human Serv, Rosenberg, TX USA.
[Irvin, K.; Da Silva, A. J.; Fields, A.; Wellman, A.; Beal, J.; Lance, S.] US FDA, College Pk, MD USA.
RP Abanyie, F (reprint author), Ctr Dis Control & Prevent, Ctr Global Hlth, Div Parasit Dis & Malaria, Med Epidemiol,Parasit Dis Branch, 1600 Clifton Rd,Mail Stop A-06, Atlanta, GA 30333 USA.
EM why6@cdc.gov
FU Centers for Disease Control and Prevention, Center for Global Health,
Division of Parasitic Diseases and Malaria; National Center for Emerging
and Zoonotic Infectious Diseases, Division of Foodborne, Waterborne &
Environmental Diseases
FX This work was supported by the Centers for Disease Control and
Prevention, Center for Global Health, Division of Parasitic Diseases and
Malaria, and the National Center for Emerging and Zoonotic Infectious
Diseases, Division of Foodborne, Waterborne & Environmental Diseases.
NR 22
TC 6
Z9 6
U1 2
U2 8
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0950-2688
EI 1469-4409
J9 EPIDEMIOL INFECT
JI Epidemiol. Infect.
PD DEC
PY 2015
VL 143
IS 16
BP 3451
EP 3458
DI 10.1017/S0950268815000370
PG 8
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA CW7JC
UT WOS:000365173600010
PM 25865140
ER
PT J
AU Scott, VN
Powell, M
Cabrera, J
Carullo, ME
Martinez, I
Lohachoompol, V
AF Scott, Virginia N.
Powell, Mark
Cabrera, Josefina
Carullo, Maria E.
Martinez, Ines
Lohachoompol, Virachnee
TI Development of microbiological criteria to assess the acceptability of a
food lot - An example for milk powder
SO FOOD CONTROL
LA English
DT Article
DE Microbiological criterion; Sampling plans; Lot acceptability;
Verification; Milk powder
ID PERFORMANCE
AB Milk powder to be consumed without further treatment to inactivate microorganisms was selected to illustrate the process for establishing and applying a microbiological criterion to assess the acceptability of a food lot. Example criteria (size of analytical unit, sampling plan and limits) were specified for mesophilic aerobic colony count and Enterobacteriaceae as indicators of the adequacy of Good Hygienic Practices and for Salmonella as a food safety criterion. Performance characteristics were determined for each criterion using four values for standard deviation of the microbial counts to illustrate how sampling plan performance depends on the within-lot standard deviation, which is uncertain for any given lot and varies among lots. Methods of analysis were specified. A description of how to interpret the results and examples of actions that could be taken by food business operators and competent authorities are provided. (C) 2014 Published by Elsevier Ltd.
C1 [Scott, Virginia N.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Powell, Mark] USDA, Off Risk Assessment & Cost Benefit Anal, Washington, DC 20250 USA.
[Cabrera, Josefina] Minist Hlth, Natl Food Inst, INAL ANMAT, Microbiol, Buenos Aires, DF, Argentina.
[Carullo, Maria E.] Agri Food SENASA, Natl Serv Hlth & Qual, RA-1063 Caba, Argentina.
[Martinez, Ines] Technol Lab Uruguay Latu, Montevideo 11500, Uruguay.
[Lohachoompol, Virachnee] Minist Agr & Cooperat, Natl Bur Agr Commod & Food Stand, Bangkok 10900, Thailand.
RP Scott, VN (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS-300, College Pk, MD 20740 USA.
EM jennyscott@verizon.net
NR 12
TC 2
Z9 2
U1 1
U2 11
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0956-7135
EI 1873-7129
J9 FOOD CONTROL
JI Food Control
PD DEC
PY 2015
VL 58
SI SI
BP 12
EP 16
DI 10.1016/j.foodcont.2014.09.026
PG 5
WC Food Science & Technology
SC Food Science & Technology
GA CW5TI
UT WOS:000365059100003
ER
PT J
AU Zhou, J
Zhang, ZW
Li, ZH
Zhang, J
AF Zhou, Jie
Zhang, Zhiwei
Li, Zhaohai
Zhang, Jun
TI Coarsened Propensity Scores and Hybrid Estimators for Missing Data and
Causal Inference
SO INTERNATIONAL STATISTICAL REVIEW
LA English
DT Article
DE Double robustness; inverse probability weighting; outcome regression;
propensity score; stratification
ID DOUBLY ROBUST ESTIMATION; INCOMPLETE DATA; MODELS; EPIDEMIOLOGY;
SMOKING; BIAS
AB In the areas of missing data and causal inference, there is great interest in doubly robust (DR) estimators that involve both an outcome regression (RG) model and a propensity score (PS) model. These DR estimators are consistent and asymptotically normal if either model is correctly specified. Despite their theoretical appeal, the practical utility of DR estimators has been disputed (e.g. Kang and Schaffer, Statistical Science 2007; 22: 523-539). One of the major concerns is the possibility of erratic estimates resulting from near-zero denominators due to extreme values of the estimated PS. In contrast, the usual RG estimator based on the RG model alone is efficient when the RG model is correct and generally more stable than the DR estimators, although it can be biased when the RG model is incorrect. In light of the unique advantages of the RG and DR estimators, we propose a class of hybrid estimators that attempt to strike a reasonable balance between the RG and DR estimators. These hybrid estimators are motivated by heuristic arguments that coarsened PS estimates are less likely to take extreme values and less sensitive to misspecification of the PS model than the original model-based PS estimates. The proposed estimators are compared with existing estimators in simulation studies and illustrated with real data from a large observational study on obstetric labour progression and birth outcomes.
C1 [Zhou, Jie; Zhang, Zhiwei] US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Div Biostat, Silver Spring, MD 20993 USA.
[Li, Zhaohai] George Washington Univ, Dept Stat, Washington, DC 20052 USA.
[Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, MOE, Shanghai 200030, Peoples R China.
[Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Shanghai Key Lab Childrens Environm Hlth, Shanghai 200030, Peoples R China.
RP Zhou, J (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Div Biostat, Silver Spring, MD 20993 USA.
EM jack.zhou@fda.hhs.gov
NR 30
TC 0
Z9 0
U1 3
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0306-7734
EI 1751-5823
J9 INT STAT REV
JI Int. Stat. Rev.
PD DEC
PY 2015
VL 83
IS 3
BP 449
EP 471
DI 10.1111/insr.12082
PG 23
WC Statistics & Probability
SC Mathematics
GA CW6NP
UT WOS:000365114600006
ER
PT J
AU Wolkin, A
Patterson, JR
Harris, S
Soler, E
Burrer, S
McGeehin, M
Greene, S
AF Wolkin, Amy
Patterson, Jennifer Rees
Harris, Shelly
Soler, Elena
Burrer, Sherry
McGeehin, Michael
Greene, Sandra
TI Reducing Public Health Risk During Disasters: Identifying Social
Vulnerabilities
SO JOURNAL OF HOMELAND SECURITY AND EMERGENCY MANAGEMENT
LA English
DT Article
DE at-risk; disaster; emergency management; public health; social
vulnerabilities
ID CLIMATE-CHANGE
AB All regions of the US experience disasters which result in a number of negative public health consequences. Some populations have higher levels of social vulnerability and, thus, are more likely to experience negative impacts of disasters including emotional distress, loss of property, illness, and death. To mitigate the impact of disasters on at-risk populations, emergency managers must be aware of the social vulnerabilities within their community. This paper describes a qualitative study which aimed to understand how emergency managers identify social vulnerabilities, also referred to as at-risk populations, in their populations and barriers and facilitators to current approaches. Findings suggest that although public health tools have been developed to aid emergency managers in identifying at-risk populations, they are not being used consistently. Emergency managers requested more information on the availability of tools as well as guidance on how to increase ability to identify at-risk populations.
C1 [Wolkin, Amy; Burrer, Sherry] Ctr Dis Control & Prevent, Div Environm Hazards & Hlth Effects, Natl Ctr Environm Hlth, Atlanta, GA USA.
[Patterson, Jennifer Rees; Soler, Elena] SciMetrika LLC, Durham, NC USA.
[Harris, Shelly] US FDA, Silver Spring, MD USA.
[McGeehin, Michael] RTI Int, Atlanta, GA USA.
[Greene, Sandra] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27515 USA.
RP Wolkin, A (reprint author), 4770 Buford Highway, Chamblee, GA 30341 USA.
EM ajf9@cdc.gov
NR 17
TC 0
Z9 0
U1 2
U2 4
PU WALTER DE GRUYTER GMBH
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 2194-6361
EI 1547-7355
J9 J HOMEL SECUR EMERG
JI J. Homel. Secur. Emerg. Manag.
PD DEC
PY 2015
VL 12
IS 4
BP 809
EP 822
DI 10.1515/jhsem-2014-0104
PG 14
WC Public Administration
SC Public Administration
GA CX1AX
UT WOS:000365429700005
ER
PT J
AU Leonard, SR
Mammel, MK
Lacher, DW
Elkins, CA
AF Leonard, Susan R.
Mammel, Mark K.
Lacher, David W.
Elkins, Christopher A.
TI Application of Metagenomic Sequencing to Food Safety: Detection of Shiga
Toxin-Producing Escherichia coli on Fresh Bagged Spinach
SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY
LA English
DT Article
ID COMMUNITIES; OUTBREAKS; CLASSIFICATION; VEGETABLES; O157-H7; GROWTH
AB Culture-independent diagnostics reduce the reliance on traditional ( and slower) culture-based methodologies. Here we capitalize on advances in next-generation sequencing (NGS) to apply this approach to food pathogen detection utilizing NGS as an analytical tool. In this study, spiking spinach with Shiga toxin-producing Escherichia coli (STEC) following an established FDA culture-based protocol was used in conjunction with shotgun metagenomic sequencing to determine the limits of detection, sensitivity, and specificity levels and to obtain information on the microbiology of the protocol. We show that an expected level of contamination (similar to 10 CFU/100 g) could be adequately detected (including key virulence determinants and strain-level specificity) within 8 h of enrichment at a sequencing depth of 10,000,000 reads. We also rationalize the relative benefit of static versus shaking culture conditions and the addition of selected antimicrobial agents, thereby validating the long-standing culture-based parameters behind such protocols. Moreover, the shotgun metagenomic approach was informative regarding the dynamics of microbial communities during the enrichment process, including initial surveys of the microbial loads associated with bagged spinach; the microbes found included key genera such as Pseudomonas, Pantoea, and Exiguobacterium. Collectively, our metagenomic study highlights and considers various parameters required for transitioning to such sequencing-based diagnostics for food safety and the potential to develop better enrichment processes in a high-throughput manner not previously possible. Future studies will investigate new species-specific DNA signature target regimens, rational design of medium components in concert with judicious use of additives, such as antibiotics, and alterations in the sample processing protocol to enhance detection.
C1 [Leonard, Susan R.; Mammel, Mark K.; Lacher, David W.; Elkins, Christopher A.] US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA.
RP Elkins, CA (reprint author), US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA.
EM chris.elkins@fda.hhs.gov
FU Oak Ridge Institute for Science Education
FX This research was funded in part by the Oak Ridge Institute for Science
Education.
NR 24
TC 7
Z9 7
U1 2
U2 36
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0099-2240
EI 1098-5336
J9 APPL ENVIRON MICROB
JI Appl. Environ. Microbiol.
PD DEC
PY 2015
VL 81
IS 23
BP 8183
EP 8191
DI 10.1128/AEM.02601-15
PG 9
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA CW1TY
UT WOS:000364775700023
PM 26386062
ER
PT J
AU Brock, TM
Sidaginamale, R
Rushton, S
Nargol, AVF
Bowsher, JG
Savisaar, C
Joyce, TJ
Deehan, DJ
Lord, JK
Langton, DJ
AF Brock, Timothy M.
Sidaginamale, Raghavendra
Rushton, Steven
Nargol, Antoni V. F.
Bowsher, John G.
Savisaar, Christina
Joyce, Tom J.
Deehan, David J.
Lord, James K.
Langton, David J.
TI Shorter, rough trunnion surfaces are associated with higher taper wear
rates than longer, smooth trunnion surfaces in a contemporary large head
metal-on-metal total hip arthroplasty system
SO JOURNAL OF ORTHOPAEDIC RESEARCH
LA English
DT Article
DE metal-on-metal; taper-junction; arthroplasty; explant analysis
ID FAILURE RATES; REPLACEMENT; TOPOGRAPHY; JUNCTION
AB Taper wear at the head-neck junction is a possible cause of early failure in large head metal-on-metal (LH-MoM) hip replacements. We hypothesized that: (i) taper wear may be more pronounced in certain product designs; and (ii) an increased abductor moment arm may be protective. The tapers of 104 explanted LH-MoM hip replacements revised for adverse reaction to metal debris (ARMD) from a single manufacturer were analyzed for linear and volumetric wear using a co-ordinate measuring machine. The mated stem was a shorter 12/14, threaded trunnion (n=72) or a longer, smooth 11/13 trunnion (n=32). The abductor moment arm was calculated from pre-revision radiographs. Independent predictors of linear and volumetric wear included taper angle, stem type, and the horizontal moment arm. Tapers mated with the threaded 12/14 trunnion had significantly higher rates of volumetric wear (0.402mm(3)/yr vs. 0.123mm(3)/yr [t=-2.145, p=0.035]). There was a trend to larger abductor moment arms being protective (p=0.055). Design variation appears to play an important role in taper-trunnion junction failure. We recommend that surgeons bear these findings in mind when considering the use of a short, threaded trunnion with a cobalt-chromium head. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1868-1874, 2015.
C1 [Brock, Timothy M.; Sidaginamale, Raghavendra; Rushton, Steven; Joyce, Tom J.; Deehan, David J.] Newcastle Univ, Newcastle Upon Tyne, Tyne & Wear, England.
[Nargol, Antoni V. F.] Univ Hosp North Tees, Dept Orthopaed, North Tees, England.
[Bowsher, John G.; Savisaar, Christina] US FDA, Silver Spring, MD USA.
[Lord, James K.] Calif Polytech State Univ San Luis Obispo, Biomed & Gen Engn, San Luis Obispo, CA 93407 USA.
[Langton, David J.] Univ Hosp North Tees, North Tees Explant Ctr, North Tees, England.
RP Langton, DJ (reprint author), Univ Hosp North Tees, North Tees Explant Ctr, North Tees, England.
EM djlangton22@doctors.org.uk
OI Joyce, Thomas/0000-0002-8497-5790
FU Food and Drug Administration [HHSF223201300925P]
FX Grant sponsor: Food and Drug Administration; Grant number:
HHSF223201300925P.
NR 16
TC 5
Z9 5
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0736-0266
EI 1554-527X
J9 J ORTHOP RES
JI J. Orthop. Res.
PD DEC
PY 2015
VL 33
IS 12
BP 1868
EP 1874
DI 10.1002/jor.22970
PG 7
WC Orthopedics
SC Orthopedics
GA CV4LU
UT WOS:000364239400018
PM 26135357
ER
PT J
AU Khurana, M
Silverstein, D
AF Khurana, Mona
Silverstein, Douglas M.
TI Etiology and management of dyslipidemia in children with chronic kidney
disease and end-stage renal disease
SO PEDIATRIC NEPHROLOGY
LA English
DT Review
DE Dyslipidemia; Chronic kidney disease; Cardiovascular disease; Lifestyle
change; Dietary counseling; Statin therapy; Adverse events
ID DENSITY-LIPOPROTEIN CHOLESTEROL; AMBULATORY PERITONEAL-DIALYSIS;
CHILDHOOD NEPHROTIC SYNDROME; CORONARY-ARTERY-DISEASE; ESTER TRANSFER
PROTEIN; APOLIPOPROTEIN A-IV; CARDIOVASCULAR RISK;
HEMODIALYSIS-PATIENTS; LIPID ABNORMALITIES; CYCLOSPORINE THERAPY
AB Lipids are essential components of cell membranes, contributing to cell fuel, myelin formation, subcellular organelle function, and steroid hormone synthesis. Children with chronic kidney disease (CKD) and end-stage renal disease (ESRD) exhibit various co-morbidities, including dyslipidemia. The prevalence of dyslipidemias in children with CKD and ESRD is high, being present in 39-65 % of patients. Elevated lipid levels in children without renal disease are a risk factor for cardiovascular disease (CVD), while the risk for CVD in pediatric CKD/ESRD is unclear. The pathogenesis of dyslipidemia in CKD features various factors, including increased levels of triglycerides, triglyceride-rich lipoproteins, apolipoprotein C3 (ApoC-III), decreased levels of cholesterylester transfer protein and high-density lipoproteins, and aberrations in serum very low-density and intermediate-density lipoproteins. If initial risk assessment indicates that a child with advanced CKD has 2 or more co-morbidities for CVD, first-line treatment should consist of non-pharmacologic management such as therapeutic lifestyle changes and dietary counseling. Pharmacologic treatment of dyslipidemia may reduce the incidence of CVD in children with CKD/ESRD, but randomized trials are lacking. Statins are the only class of lipid-lowering drugs currently approved by the U.S. Food and Drug Administration (FDA) for use in the pediatric population. FDA-approved pediatric labeling for these drugs is based on results from placebo-controlled trial results, showing 30-50 % reductions in baseline low-density lipoprotein cholesterol. Although statins are generally well tolerated in adults, a spectrum of adverse events has been reported with their use in both the clinical trial and post-marketing settings.
C1 [Khurana, Mona] US FDA, Ctr Drug Evaluat, Div Nonprescript Regulat Dev, Silver Spring, MD 20993 USA.
[Khurana, Mona] US FDA, Res Off New Drugs, Div Nonprescript Regulat Dev, Silver Spring, MD 20993 USA.
[Silverstein, Douglas M.] US FDA, Ctr Devices & Radiol Hlth, Div Reprod Gastrorenal & Urol Devices, Renal Devices Branch, Silver Spring, MD 20993 USA.
RP Silverstein, D (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Reprod Gastrorenal & Urol Devices, Renal Devices Branch, 10903 New Hampshire Ave,Bldg 66-G252, Silver Spring, MD 20993 USA.
EM dsilverstein2001@yahoo.com
NR 98
TC 2
Z9 2
U1 3
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0931-041X
EI 1432-198X
J9 PEDIATR NEPHROL
JI Pediatr. Nephrol.
PD DEC
PY 2015
VL 30
IS 12
BP 2073
EP 2084
DI 10.1007/s00467-015-3075-9
PG 12
WC Pediatrics; Urology & Nephrology
SC Pediatrics; Urology & Nephrology
GA CU9OC
UT WOS:000363872900003
PM 25801207
ER
PT J
AU Mans, DJ
Ye, HP
Dunn, JD
Kolinski, RE
Long, DS
Phatak, NL
Ghasriani, H
Buhse, LF
Kauffman, JF
Keire, DA
AF Mans, Daniel J.
Ye, Hongping
Dunn, Jamie D.
Kolinski, Richard E.
Long, Dianna S.
Phatak, Nisarga L.
Ghasriani, Houman
Buhse, Lucinda F.
Kauffman, John F.
Keire, David A.
TI Synthesis and detection of N-sulfonated oversulfated chondroitin sulfate
in marketplace heparin
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
DE Heparin; Oversulfated chondroitin sulfate; Nuclear magnetic resonance;
High-performance liquid chromatography
ID ADVERSE CLINICAL EVENTS; CONTAMINANTS
AB N-sulfonated oversulfated chondroitin sulfate (NS-OSCS), recently reported as a potential threat to the heparin supply, was prepared along with its intermediate derivatives. All compounds were spiked into marketplace heparin and subjected to United States Pharmacopeia (USP) identification assays for heparin (proton nuclear magnetic resonance [H-1 NMR], chromatographic identity, % galactosamine [%GaIN], anti-factor Ha potency, and anti-factor Xa/IIa ratio). The U.S. Food and Drug Administration (FDA) strong-anionic exchange high-performance liquid chromatography (SAX HPLC) method resolved NS-OSCS from heparin and OSCS and had a limit of detection of 0.26% (w/w) NS-OSCS. The %GaIN test was sensitive to the presence of NS-OSCS in heparin. Therefore, current USP heparin monograph tests (i.e., SAX-HPLC and %GaIN) detect the presence of NS-OSCS in heparin. Published by Elsevier Inc.
C1 [Mans, Daniel J.; Ye, Hongping; Dunn, Jamie D.; Kolinski, Richard E.; Long, Dianna S.; Phatak, Nisarga L.; Ghasriani, Houman; Buhse, Lucinda F.; Kauffman, John F.; Keire, David A.] US FDA, Div Pharmaceut Anal, St Louis, MO 63110 USA.
RP Mans, DJ (reprint author), US FDA, Div Pharmaceut Anal, St Louis, MO 63110 USA.
EM daniel.mans@fda.hhs.gov
NR 18
TC 1
Z9 1
U1 8
U2 24
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0003-2697
EI 1096-0309
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD DEC 1
PY 2015
VL 490
BP 52
EP 54
DI 10.1016/j.ab.2015.08.003
PG 3
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA CU2NP
UT WOS:000363360500008
PM 26278168
ER
PT J
AU Cokic, VP
Mojsilovic, S
Jaukovic, A
Kraguljac-Kurtovic, N
Mojsilovic, S
Sefer, D
Ajtic, OM
Milosevic, V
Bogdanovic, A
Dikic, D
Milenkovic, P
Puri, RK
AF Cokic, Vladan P.
Mojsilovic, Slavko
Jaukovic, Aleksandra
Kraguljac-Kurtovic, Nada
Mojsilovic, Sonja
Sefer, Dijana
Ajtic, Olivera Mitrovic
Milosevic, Violeta
Bogdanovic, Andrija
Dikic, Dragoslava
Milenkovic, Pavle
Puri, Raj K.
TI Gene expression profile of circulating CD34(+) cells and granulocytes in
chronic myeloid leukemia
SO BLOOD CELLS MOLECULES AND DISEASES
LA English
DT Article
DE CD34(+) cells; Granulocytes; Chronic myeloid leukemia; Microarray
analysis
ID CHRONIC MYELOGENOUS LEUKEMIA; MOLECULAR SIGNATURE; HEMATOPOIETIC STEM;
PROGENITOR CELLS; CHRONIC PHASE; CML; REVEALS
AB Purpose: We compared the gene expression profile of peripheral blood CD34(+) cells and granulocytes in subjects with chronic myeloid leukemia (CML), with the accent on signaling pathways affected by BCR-ABL oncogene.
Methods: The microarray analyses have been performed in circulating CD34(+) cells and granulocytes from peripheral blood of 7 subjects with CML and 7 healthy donors. All studied BCR-ABL positive CML patients were in chronic phase, with a mean value of 2012 +/- SD of CD34(+) cells/mu l in peripheral blood.
Results: The gene expression profile was more prominent in CML CD34(+) cells (3553 genes) compared to granulocytes (2701 genes). The 41 and 39 genes were significantly upregulated in CML CD34(+) cells (HINT1, TXN, SERBP1) and granulocytes, respectively. BCR-ABL oncogene activated PI3K/AKT and MAPK signaling through significant upregulation of PTPN11, CDK4/6, and MYC and reduction of E2F1, KRAS, and NFKBIA gene expression in CD34(+) cells. Among genes linked to the inhibition of cellular proliferation by BCR-ABL inhibitor Imatinib, the FOS and STAT1 demonstrated significantly decreased expression in CML.
Conclusion: The presence of BCR-ABL fusion gene doubled the expression quantity of genes involved in the regulation of cell cycle, proliferation and apoptosis of CD34(+) cells. These results determined the modified genes in PI3K/AKT and MAPK signaling of CML subjects. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Cokic, Vladan P.; Mojsilovic, Slavko; Jaukovic, Aleksandra; Mojsilovic, Sonja; Ajtic, Olivera Mitrovic; Dikic, Dragoslava; Milenkovic, Pavle] Univ Belgrade, Inst Med Res, Belgrade 11129, Serbia.
[Kraguljac-Kurtovic, Nada; Sefer, Dijana; Milosevic, Violeta; Bogdanovic, Andrija] Clin Ctr Serbia, Clin Hematol, Belgrade, Serbia.
[Bogdanovic, Andrija] Univ Belgrade, Fac Med, Belgrade 11129, Serbia.
[Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
RP Cokic, VP (reprint author), Univ Belgrade, Inst Med Res, Lab Expt Hematol, Dr Subotica 4, Belgrade 11129, Serbia.
EM vl@imi.bg.ac.rs
FU Intramural Research Program of Alan N. Schechter at the National
Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda
[Z01 DK025016-33]; Serbian Ministry of Education, Science and
Technological Development [175053]
FX This research was supported by the Intramural Research Program of Alan
N. Schechter (Z01 DK025016-33) at the National Institute of Diabetes and
Digestive and Kidney Diseases, NIH, Bethesda, and by a grant from the
Serbian Ministry of Education, Science and Technological Development
[No. 175053].
NR 18
TC 0
Z9 0
U1 1
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1079-9796
EI 1096-0961
J9 BLOOD CELL MOL DIS
JI Blood Cells Mol. Dis.
PD DEC
PY 2015
VL 55
IS 4
BP 373
EP 381
DI 10.1016/j.bcmd.2015.08.002
PG 9
WC Hematology
SC Hematology
GA CU2MR
UT WOS:000363358100016
PM 26460262
ER
PT J
AU Petrochenko, PE
Kumar, G
Fu, WJ
Zhang, Q
Zheng, JW
Liang, CD
Goering, PL
Narayan, RJ
AF Petrochenko, Peter E.
Kumar, Girish
Fu, Wujun
Zhang, Qin
Zheng, Jiwen
Liang, Chengdu
Goering, Peter L.
Narayan, Roger J.
TI Nanoporous Aluminum Oxide Membranes Coated with Atomic Layer
Deposition-Grown Titanium Dioxide for Biomedical Applications: An In
Vitro Evaluation
SO JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
LA English
DT Article
DE Anodized Aluminum Oxide (AAO); Titanium Dioxide (TiO2); Atomic Layer
Deposition (ALD); Nanoporous Membrane; Protein Adsorption;
Biocompatibility; Cytotoxicity TNF-Alpha
ID PARTICLES; TIO2; OSTEOBLAST; RESPONSES; ALLOY; ZNO
AB The surface topographies of nanoporous anodic aluminum oxide (AAO) and titanium dioxide (TiO2) membranes have been shown to modulate cell response in orthopedic and skin wound repair applications. In this study, we: (1) demonstrate an improved atomic layer deposition (ALD) method for coating the porous structures of 20, 100, and 200 nm pore diameter AAO with nanometer-thick layers of TiO2 and (2) evaluate the effects of uncoated AAO and TiO2-coated AAO on cellular responses. The TiO2 coatings were deposited on the AAO membranes without compromising the openings of the nanoscale pores. The 20 nm TiO2-coated membranes showed the highest amount of initial protein adsorption via the micro bicinchoninic acid (micro-BOA) assay; all of the TiO2-coated membranes showed slightly higher protein adsorption than the uncoated control materials. Cell viability, proliferation, and inflammatory responses on the TiO2-coated AAO membranes showed no adverse outcomes. For all of the tested surfaces, normal increases in proliferation (DNA content) of L929 fibroblasts were observed over from 4 hours to 72 hours. No increases in TNF-alpha production were seen in RAW 264.7 macrophages grown on TiO2-coated AAO membranes compared to uncoated AAO membranes and tissue culture polystyrene (TOPS) surfaces. Both uncoated AAO membranes and TiO2-coated AAO membranes showed no significant effects on cell growth and inflammatory responses. The results suggest that TiO2-coated AAO may serve as a reasonable prototype material for the development of nanostructured wound repair devices and orthopedic implants.
C1 [Petrochenko, Peter E.; Kumar, Girish; Zhang, Qin; Zheng, Jiwen; Goering, Peter L.] US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Petrochenko, Peter E.; Narayan, Roger J.] UNC NCSU Joint Dept Biomed Engn, Raleigh, NC 27965 USA.
[Fu, Wujun; Liang, Chengdu] Oak Ridge Natl Lab, Ctr Nanophase Mat Sci, Oak Ridge, TN 37831 USA.
RP Narayan, RJ (reprint author), UNC NCSU Joint Dept Biomed Engn, Raleigh, NC 27965 USA.
EM roger_narayan@unc.edu
FU NSF [1041375]; United States Department of Energy's Division of
Scientific User Facilities
FX Peter E. Petrochenko is supported in part by NSF Award #1041375. ALD
coating of TiO2 on AAO was conducted at the Center for
Nanophase Materials Sciences, which is sponsored at Oak Ridge National
Laboratory by the United States Department of Energy's Division of
Scientific User Facilities.
NR 34
TC 2
Z9 2
U1 9
U2 82
PU AMER SCIENTIFIC PUBLISHERS
PI VALENCIA
PA 26650 THE OLD RD, STE 208, VALENCIA, CA 91381-0751 USA
SN 1550-7033
EI 1550-7041
J9 J BIOMED NANOTECHNOL
JI J. Biomed. Nanotechnol.
PD DEC
PY 2015
VL 11
IS 12
BP 2275
EP 2285
DI 10.1166/jbn.2015.2169
PG 11
WC Nanoscience & Nanotechnology; Materials Science, Biomaterials
SC Science & Technology - Other Topics; Materials Science
GA CS2WC
UT WOS:000361931700016
PM 26510320
ER
PT J
AU Messer, K
Vijayaraghavan, M
White, MM
Shi, YY
Chang, C
Conway, KP
Hartman, A
Schroeder, MJ
Compton, WM
Pierce, JP
AF Messer, Karen
Vijayaraghavan, Maya
White, Martha M.
Shi, Yuyan
Chang, Cindy
Conway, Kevin P.
Hartman, Anne
Schroeder, Megan J.
Compton, Wilson M.
Pierce, John P.
TI Cigarette smoking cessation attempts among current US smokers who also
use smokeless tobacco
SO ADDICTIVE BEHAVIORS
LA English
DT Article
DE Smokeless tobacco; Smoking cessation; Poly-tobacco use
ID HARM REDUCTION; UNITED-STATES; NICOTINE DEPENDENCE; DUAL-USE;
PREVALENCE; CALIFORNIA; ADULT; PRODUCTS; SUCCESS; HEALTH
AB Introduction: Concurrent use of cigarettes and smokeless tobacco is common, but little is known regarding the association of smokeless tobacco use with cigarette smoking cessation. Dual users may have lower cigarette consumption levels, which may also play a role in smoking cessation.
Methods: The 2010-2011 Tobacco Use Supplement to the Current Population Survey included 26,760 current cigarette smokers, of which 675 concurrently used smokeless tobacco. We compared characteristics of the most recent cigarette smoking quit attempt of the past year between dual users and exclusive smokers, using multivariate regression.
Results: Dual users (45%) were more likely than exclusive smokers (37%) to have made a cigarette smoking quit attempt during the previous year (p < 0.01), even after adjusting for demographic differences and cigarette dependence levels (OR adj 1.33,95% CI 1.15-1.53). Half (48%) of dual users who made a quit attempt tried to quit "by switching to smokeless tobacco". However, once in a quit attempt, dual users relapsed more quickly than exclusive smokers (Cox regression HRadj 1.13,95% CI 1.02-1.26). There was no difference in 30-day abstinence rates on the most recent quit attempt (ORadj 1.09, 95% CI 0.88-137). For both groups, the best predictor of past 30-day abstinence was cigarette consumption level.
Conclusions: Current cigarette smokers who also use smokeless tobacco are more likely to have tried to quit, but relapse more quickly than exclusive smokers, and are not more likely to have attained 30 day smoking cessation. Prospective studies at the population level are needed. (C) 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license.
C1 [Messer, Karen; Vijayaraghavan, Maya; White, Martha M.; Shi, Yuyan; Pierce, John P.] Univ Calif San Diego, Moores UCSD Canc Ctr, Canc Prevent & Control Div, La Jolla, CA 92093 USA.
[Messer, Karen] Univ Calif San Diego, Div Biostat & Bioinformat, La Jolla, CA 92093 USA.
[Messer, Karen; Vijayaraghavan, Maya; Shi, Yuyan; Pierce, John P.] Univ Calif San Diego, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA.
[Chang, Cindy; Schroeder, Megan J.] US FDA, Ctr Tobacco Prod, Silver Spring, MD 20993 USA.
[Conway, Kevin P.; Compton, Wilson M.] NIDA, NIH, Bethesda, MD 20892 USA.
[Hartman, Anne] NCI, NIH, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.
RP Messer, K (reprint author), Univ Calif San Diego, Moores UCSD Canc Ctr, La Jolla, CA 92093 USA.
EM kmesser@ucsd.edu
OI Conway, Kevin/0000-0002-7638-339X
FU National Institute on Drug Abuse, National Institutes of Health; Food
and Drug Administration, Department of Health and Human Services
[HHSN271201100027C]; UC Tobacco-Related Disease Research Program
[21RT-0135]; National Cancer Institute [1R01CA172058-02]
FX This project has been funded in whole or in part with federal funds from
the National Institute on Drug Abuse, National Institutes of Health, and
the Food and Drug Administration, Department of Health and Human
Services, under contract no. HHSN271201100027C; and by UC
Tobacco-Related Disease Research Program grants 21RT-0135, and National
Cancer Institute grant no. 1R01CA172058-02. The funding sources had no
involvement in the study design, collection, analysis, or interpretation
of data, writing the manuscript and the decision to submit the
manuscript for publication.
NR 31
TC 5
Z9 5
U1 1
U2 14
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4603
EI 1873-6327
J9 ADDICT BEHAV
JI Addict. Behav.
PD DEC
PY 2015
VL 51
BP 113
EP 119
DI 10.1016/j.addbeh.2015.06.045
PG 7
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA CR8DI
UT WOS:000361580900019
PM 26253939
ER
PT J
AU Hu, L
Grim, CJ
Franco, AA
Jarvis, KG
Sathyamoorthy, V
Kothary, MH
McCardell, BA
Tall, B
AF Hu, Lan
Grim, Christopher J.
Franco, Augusto A.
Jarvis, Karen G.
Sathyamoorthy, Vengopal
Kothary, Mahendra H.
McCardell, Barbara A.
Tall, Ben D.
TI Analysis of the cellulose synthase operon genes, bcsA, bcsB, and bcsC in
Cronobacter species: Prevalence among species and their roles in biofilm
formation and cell-cell aggregation
SO FOOD MICROBIOLOGY
LA English
DT Article
DE Cronobacter; Cellulose; bcsABC; Biofilm formation; Cell-cell
aggregation; Rugosity
ID POWDERED INFANT FORMULA; ENTEROBACTER-SAKAZAKII; ESCHERICHIA-COLI;
EXTRACELLULAR-MATRIX; GENUS CRONOBACTER; STAINLESS-STEEL; INFECTIONS;
SPP.; BIOSYNTHESIS; TYPHIMURIUM
AB Cronobacter species are emerging food-borne pathogens that cause severe sepsis, meningitis, and necrotizing entercolitis in neonates and infants. Bacterial pathogens such as Escherichia coli and Salmonella species produce extracellular cellulose which has been shown to be involved in rugosity, biofilm formation, and host colonization. In this study the distribution and prevalence of cellulose synthase operon genes (bcsABZC) were determined by polymerase chain reaction (PCR) analysis in 231 Cronobacter strains isolated from clinical, food, environmental, and unknown sources. Furthermore, bcsA and bcsB isogenic mutants were constructed in Cronobacter sakazakii BAA894 to determine their roles. In calcofluor binding assays bcsA and bcsB mutants did not produce cellulose, and their colonial morphotypes were different to that of the parent strain. Biofilm formation and bacterial cell-cell aggregation were significantly reduced in bcsA and bcsB mutants compared to the parental strain. bcsA or bcsAB PCR-negative strains of C. sakazakii did not bind calcofluor, and produced less biofilm and cell-cell aggregation compared to strains possessing bcsAB genes. These data indicated that Cronobacter bcsABZC were present in all clinical isolates and most of food and environmental isolates. bcsA and bcsB genes of Cronobacter were necessary to produce cellulose, and were involved in biofilm formation and cellecell aggregation. Published by Elsevier Ltd.
C1 [Hu, Lan; Grim, Christopher J.; Franco, Augusto A.; Jarvis, Karen G.; Sathyamoorthy, Vengopal; Kothary, Mahendra H.; McCardell, Barbara A.; Tall, Ben D.] US FDA, CFSAN, Laurel, MD 20708 USA.
RP Hu, L (reprint author), US FDA, CFSAN, Laurel, MD 20708 USA.
EM lan16686@yahoo.com
OI Tall, Ben/0000-0003-0399-3629
NR 44
TC 3
Z9 3
U1 4
U2 44
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0740-0020
EI 1095-9998
J9 FOOD MICROBIOL
JI Food Microbiol.
PD DEC
PY 2015
VL 52
BP 97
EP 105
DI 10.1016/j.fm.2015.07.007
PG 9
WC Biotechnology & Applied Microbiology; Food Science & Technology;
Microbiology
SC Biotechnology & Applied Microbiology; Food Science & Technology;
Microbiology
GA CQ5OA
UT WOS:000360653500012
PM 26338122
ER
PT J
AU Al-Ghabeish, M
Xu, XM
Krishnaiah, YSR
Rahman, Z
Yang, Y
Khan, MA
AF Al-Ghabeish, Manar
Xu, Xiaoming
Krishnaiah, Yellela S. R.
Rahman, Ziyaur
Yang, Yang
Khan, Mansoor A.
TI Influence of drug loading and type of ointment base on the in vitro
performance of acyclovir ophthalmic ointment
SO INTERNATIONAL JOURNAL OF PHARMACEUTICS
LA English
DT Article
DE Ophthalmic ointment; Performance tests; Acyclovir; Transcorneal
permeation; Semisolid dosage form; Drug retention in cornea; Drug
release
ID RABBIT CORNEA; HERPES-SIMPLEX; PERMEATION; RELEASE; TRANSPORTER;
EPITHELIUM; MECHANISM; DELIVERY; OPTISOL; STORAGE
AB The availability of in vitro performance tests such as in vitro drug release testing (IVRT) and in vitro permeation testing (IVPT) are critical to comprehensively assure consistent delivery of the active component(s) from semisolid ophthalmic drug products. The objective was to study the impact of drug loading and type of ointment base on the in vitro performance (IVRT and IVPT) of ophthalmic ointments using acyclovir as a model drug candidate. The in vitro drug release for the ointments was evaluated using a modified USP apparatus 2 with Enhancer cells. The transcorneal permeation was carried out using rabbit cornea on modified vertical Franz cells. The drug retention in cornea (DRC) was also determined at the end of transcorneal drug permeation study. The in vitro drug release, transcorneal drug permeation as well as DRC exhibited a proportional increase with increasing drug loading in the ointment. On comparing the in vitro drug release profile with transcorneal permeation profile, it appears that drug release from the ointment is controlling acyclovir transport through the cornea. Furthermore, enhanced in vitro transcorneal permeation relative to the in vitro drug release underscores the importance of the interplay between the physiology of the ocular tissue and ointment formulation. The results indicated that IVRT and IVPT could be used to discriminate the impact of changes in drug load and formulation composition of ophthalmic ointments. (C) 2015 Published by Elsevier B.V.
C1 [Al-Ghabeish, Manar; Xu, Xiaoming; Krishnaiah, Yellela S. R.; Rahman, Ziyaur; Yang, Yang; Khan, Mansoor A.] CDER OPQ OTR DPQR, Food & Drug Adm, Silver Spring, MD 20993 USA.
RP Khan, MA (reprint author), CDER OPQ OTR DPQR, Food & Drug Adm, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM Mansoor.Khan@fda.hhs.gov
OI Rahman, Ziyaur/0000-0002-0402-825X
NR 38
TC 2
Z9 2
U1 3
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5173
EI 1873-3476
J9 INT J PHARMACEUT
JI Int. J. Pharm.
PD NOV 30
PY 2015
VL 495
IS 2
BP 783
EP 791
DI 10.1016/j.ijpharm.2015.08.096
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CV2YD
UT WOS:000364124100018
PM 26343911
ER
PT J
AU Shen, J
Choi, S
Qu, W
Wang, Y
Burgess, DJ
AF Shen, Jie
Choi, Stephanie
Qu, Wen
Wang, Yan
Burgess, Diane J.
TI In vitro-in vivo correlation of parenteral risperidone polymeric
microspheres
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE Poly(lactic-co-glycolic acid) (PLGA) microspheres; Manufacturing
differences; In vitro and in vivo correlation; Risperidone; USP
apparatus 4; Level A
ID SUSTAINED-RELEASE PRODUCTS; DRUG-DELIVERY; RISPERDAL(R) CONSTA(R); PLGA
MICROSPHERES; QUALITY-CONTROL; FORMULATION; MICROENCAPSULATION;
PHARMACOKINETICS; MICROPARTICLES; SYSTEMS
AB The objective of the present study was to determine whether an in vitro-in vivo correlation (IVIVC) can be established for polymeric microspheres that are equivalent in formulation composition but prepared with different manufacturing processes. Risperidone was chosen as a model therapeutic and poly(lactic-co-glycolic acid) (PLGA) with similar molecular weight as that used in the commercial product Risperdal (R) Consta (R) was used to prepare risperidone microspheres. Various manufacturing processes were investigated to produce the risperidone microspheres with similar drug loading (approx. 37%) but distinctly different physicochemical properties (e.g. porosity, particle size and particle size distribution). In vitro release of the risperidone microspheres was investigated using different release testing methods (such as sample-and-separate and USP apparatus 4). In vivo pharmacokinetic profiles of the risperidone microsphere formulations following intramuscular administration were determined using a rabbit model. Furthermore, the obtained pharmacokinetic profiles were deconvoluted using the Loo-Riegelman method and the calculated in vivo release was compared with the in vitro release of these microspheres. Level A IVIVCs were established and validated for the compositionally equivalent risperidone microspheres based on the in vitro release data obtained using USP apparatus 4. The developed IVIVCs demonstrated good predictability and were robust. These results showed that the developed USP apparatus 4 method was capable of discriminating PLGA microspheres that are equivalent in formulation composition but with manufacturing differences and predicting their in vivo performance in the investigated animal model. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Shen, Jie; Burgess, Diane J.] Univ Connecticut, Sch Pharm, Storrs, CT 06269 USA.
[Choi, Stephanie; Qu, Wen; Wang, Yan] US FDA, Off Res & Stand, Off Gener Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Burgess, DJ (reprint author), Univ Connecticut, Sch Pharm, Dept Pharmaceut Sci, 69 North Eagleville Rd U3092, Storrs, CT 06269 USA.
EM d.burgess@uconn.edu
FU FDA HHS [U01 FD004931, 1U01FD004931-01]
NR 36
TC 7
Z9 7
U1 9
U2 35
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-3659
EI 1873-4995
J9 J CONTROL RELEASE
JI J. Control. Release
PD NOV 28
PY 2015
VL 218
BP 2
EP 12
DI 10.1016/j.jconrel.2015.09.051
PG 11
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA CV3OC
UT WOS:000364167500002
PM 26423236
ER
PT J
AU Moro, PL
Winiecki, S
Lewis, P
Shimabukuro, TT
Cano, M
AF Moro, Pedro L.
Winiecki, Scott
Lewis, Paige
Shimabukuro, Tom T.
Cano, Maria
TI Surveillance of adverse events after the first trivalent inactivated
influenza vaccine produced in mammalian cell culture (Flucelvax (R))
reported to the Vaccine Adverse Event Reporting System (VAERS), United
States, 2013-2015
SO VACCINE
LA English
DT Article
DE Adverse event; Cell culture; Surveillance; Trivalent inactivated
influenza vaccine; Vaccine safety
ID GUILLAIN-BARRE-SYNDROME; IMMUNIZATION SAFETY DATA; SEASONAL INFLUENZA;
ASSOCIATION; GUIDELINES; COLLECTION
AB Background: In November 2012, the first cell cultured influenza vaccine, a trivalent subunit inactivated influenza vaccine (Flucelvax (R), cclIV3), was approved in the US for adults aged >= 18 years.
Objective: To assess adverse events (AEs) after ccIIV3 reported to the US Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system.
Methods: We searched VAERS for US reports after ccIIV3 among persons vaccinated from July 1, 2013-March 31, 2015. Medical records were requested for reports classified as serious (death, hospitalization, prolonged hospitalization, disability, life-threatening-illness), and those suggesting anaphylaxis and Guillain-Barre syndrome (GBS). Physicians reviewed available information and assigned a primary clinical category using MedDRA system organ classes (SOC) to each report. Empirical Bayesian data mining was used to identify disproportional AE reporting following cclIV3.
Results: VAERS received 629 reports following ccIIV3 of which 313 were for administration of vaccine to persons <18 years. Among 309 reports with an AE documented, 19(6.1%) were serious and the most common categories were 152(49.2%) general disorders and administration site conditions (mostly injection site and systemic reactions) and 73 (23.6%) immune system disorders with two reports of anaphylaxis. Four reports of GBS were submitted. Disproportional reporting was identified for 'drug administered to patient of inappropriate age.'
Conclusions: Review of VAERS reports did not identify any concerning pattern of AEs after ccIIV3. Injection site and systemic reactions were the most commonly reported AEs, similar to the pre-licensure clinical trials. Reports following ccIIV3 in persons <18 years highlight the need for education of healthcare providers regarding approved cclIV3 use. Published by Elsevier Ltd.
C1 [Moro, Pedro L.; Lewis, Paige; Shimabukuro, Tom T.; Cano, Maria] Ctr Dis Control & Prevent, Immunizat Safety Off, Atlanta, GA 30333 USA.
[Winiecki, Scott] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
RP Moro, PL (reprint author), Ctr Dis Control & Prevent, Immunizat Safety Off, Div Healthcare Qual Promot, NCEZID, 1600 Clifton Rd,MS D26, Atlanta, GA 30333 USA.
EM pmoro@cdc.gov
NR 21
TC 3
Z9 3
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD NOV 27
PY 2015
VL 33
IS 48
BP 6684
EP 6688
DI 10.1016/j.vaccine.2015.10.084
PG 5
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA CZ0JN
UT WOS:000366791200030
PM 26518405
ER
PT J
AU Chen, RT
Shimabukuro, TT
Martin, DB
Zuber, PLP
Weibel, DM
Sturkenboom, M
AF Chen, Robert T.
Shimabukuro, Tom T.
Martin, David B.
Zuber, Patrick L. P.
Weibel, Daniel M.
Sturkenboom, Miriam
TI Enhancing vaccine safety capacity globally: A lifecycle perspective
SO VACCINE
LA English
DT Review
DE Vaccine safety; AEFI; Sustainability; Capacity building; LMICs
ID GUILLAIN-BARRE-SYNDROME; REPORTING-SYSTEM VAERS; INACTIVATED POLIOVIRUS
VACCINATION; EVENTS FOLLOWING IMMUNIZATION; MUMPS-RUBELLA VACCINE;
UNITED-STATES; ADVERSE EVENTS; INFLUENZA VACCINE; DATALINK PROJECT;
ADVISORY-COMMITTEE
AB Major vaccine safety controversies have arisen in several countries beginning in the last decades of 20th century. Such periodic vaccine safety controversies are unlikely to go away in the near future as more national immunization programs mature with near elimination of target vaccine-preventable diseases that result in relative greater prominence of adverse events following immunizations, both true reactions and temporally coincidental events. There are several ways in which vaccine safety capacity can be improved to potentially mitigate the impact of future vaccine safety controversies. This paper aims to take a "lifecycle" approach, examining some potential pre- and post-licensure opportunities to improve vaccine safety, in both developed (specifically U.S. and Europe) and low- and middle-income countries. (C) 2015 by American Journal of Preventive Medicine and Elsevier Ltd. All rights reserved.
C1 [Chen, Robert T.; Shimabukuro, Tom T.] Ctr Dis Control & Prevent, Off Infect Dis, Atlanta, GA USA.
[Martin, David B.] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
[Zuber, Patrick L. P.] WHO, CH-1211 Geneva, Switzerland.
[Weibel, Daniel M.; Sturkenboom, Miriam] Erasmus Univ, Med Ctr, Rotterdam, Netherlands.
RP Chen, RT (reprint author), 1600 Clifton Rd,MS-E45, Atlanta, GA 30333 USA.
EM bchen@cdc.gov
FU Merck; Novartis
FX This article is being published concurrently in the American Journal of
Preventive Medicine and Vaccine. The articles are identical except for
stylistic changes in keeping with each journal's style. Either of these
versions may be used in citing this article. Publication of this article
was supported by Merck and Novartis.
NR 152
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U1 1
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD NOV 27
PY 2015
VL 33
SU 4
BP D46
EP D54
DI 10.1016/j.vaccine.2015.06.073
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA CZ0BN
UT WOS:000366770200007
PM 26433922
ER
PT J
AU Gruber, MF
AF Gruber, Marion F.
TI The US FDA pregnancy lactation and labeling rule - Implications for
maternal immunization
SO VACCINE
LA English
DT Article
DE Vaccines; Maternal immunization; Pregnancy
AB The FDA has responsibility for ensuring that prescription drug and biological products including vaccines are accompanied by labeling that summarizes scientific information concerning their safe and effective use. As part of a broader effort to improve the content and format of prescription drug labeling FDA published a final rule, the Content and Format of Labeling for Human Prescription Drug and Biological Products; Requirements for Pregnancy and Lactation Labeling, referred to as the "Pregnancy and Lactation Labeling Rule (PLLR)." The most significant change to be implemented by this Rule is the removal of the letter risk categories A, B, C, D and X from all labeling, replacing them with a narrative summary of the risks of using a drug or biological product including vaccines during pregnancy. The PLLR requires an evaluation of available information about a product's use in pregnancy and provides an opportunity to update labeling when new information about use of a vaccine in pregnancy becomes available. Implementation of the provisions articulated in the PLLR, as they apply to vaccine product labeling, will require close collaboration between FDA and the vaccine manufacturer for both currently licensed vaccines and those in development. (C) 2015 The Author. Published by Elsevier Ltd.
C1 [Gruber, Marion F.] US Dept HHS, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Food & Drug Adm, Silver Spring, MD 20910 USA.
RP Gruber, MF (reprint author), US Dept HHS, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Food & Drug Adm, Silver Spring, MD 20910 USA.
EM marion.gruber@fda.hhs.gov
NR 7
TC 3
Z9 4
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD NOV 25
PY 2015
VL 33
IS 47
SI SI
BP 6499
EP 6500
DI 10.1016/j.vaccine.2015.05.107
PG 2
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA DA0LT
UT WOS:000367489300022
PM 26256527
ER
PT J
AU Janes, DW
Maher, MJ
Carroll, GT
Saylor, DM
Ellison, CJ
AF Janes, Dustin W.
Maher, Michael J.
Carroll, Gregory T.
Saylor, David M.
Ellison, Christopher J.
TI Modulating Solubility and Enhancing Reactivity of Photo-Cross-Linkable
Poly(styrene sulfonyl azide-alt-maleic anhydride) Thin Films
SO MACROMOLECULES
LA English
DT Article
ID BLOCK-COPOLYMER LITHOGRAPHY; POLYMER-FILMS; LINKING; BENZOPHENONE;
POLYETHYLENE; POLYSTYRENE; INHIBITION; OXIDATION; NETWORKS; DYNAMICS
AB To formalize our understanding of indiscriminate grafting chemistries as they pertain to cross-linkable polymers and emerging patterning technologies, we designed a new polymer, poly(styrene sulfonyl.azide-alt-maleic anhydride) (PSSMA). By modulating its solubility, it can be deposited into smooth, ultrathin films atop polar and nonpolar polymers. Upon heating above 120 degrees C or exposure to UV light, highly reactive nitrene intermediates are generated from the azide groups which form covalent adducts and cross-link the PSSMA. Azide photolysis and polymer gelation were studied in the context of a statistical model to gain insight into the network outcomes of nitrenes in a polymer film. For every azide group converted to a nitrene in ambient atmosphere, it has an 11% likelihood of grafting to another chain and a 5% chance of causing a scission. These values can be increased over 3-fold by reducing the O-2 content by 85%. Alternatively, the effects of quenching by ground-state O-2 can be mitigated by adding Michler's ketone (MK) to the film. PSSMA/MK blend films possess a 39% (+/- 13) likelihood for grafting and 29% (+/- 10) for scission. The higher ratio of scission to grafting is a consequence of the sensitized azides producing triplet-state nitrenes, which favor hydrogen abstraction. These broadly generalizable considerations will be useful to others who wish to maximize light sensitivity in related polymer systems.
C1 [Janes, Dustin W.; Saylor, David M.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Maher, Michael J.] Univ Texas Austin, Dept Chem, Austin, TX 78712 USA.
[Ellison, Christopher J.] Univ Texas Austin, McKetta Dept Chem Engn, Austin, TX 78712 USA.
[Carroll, Gregory T.] Sunstar Engn Amer, Springboro, OH 45066 USA.
RP Janes, DW (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
EM dustin.janes@fda.hhs.gov; ellison@che.utexas.edu
OI Carroll, Gregory/0000-0003-0419-4976
FU Robert A. Welch Foundation [F-1709]; National Science Foundation
Graduate Research Fellowship [DGE-1110007]
FX The findings and conclusions in this paper have not been formally
disseminated by the Food and Drug Administration and should not be
construed to represent any agency determination or policy. The mention
of commercial products, their sources, or their use in connection with
material reported herein is not to be construed as either an actual or
implied endorsement of such products by Department of Health and Human
Services. The authors thank the Robert A. Welch Foundation (Grant No.
F-1709) for generous financial support. M.J.M. thanks the National
Science Foundation Graduate Research Fellowship (Grant DGE-1110007) for
financial support. SEM was performed at the Microscopy and Imaging
Facility of the Institute for Cellular and Molecular Biology at The
University of Texas at Austin. SEC was performed and analyzed by Lars
Qvicklund and Laurie Scharp of Jordi Laboratories (Mansfield, MA). The
authors thank Chae Bin Kim, Reika Katsumata, Sunshine Zhou, and Austin
P. Lane for helpful discussions.
NR 50
TC 3
Z9 3
U1 5
U2 16
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0024-9297
EI 1520-5835
J9 MACROMOLECULES
JI Macromolecules
PD NOV 24
PY 2015
VL 48
IS 22
BP 8361
EP 8368
DI 10.1021/acs.macromol.5b01875
PG 8
WC Polymer Science
SC Polymer Science
GA CX1NW
UT WOS:000365463900032
ER
PT J
AU Burbelo, PD
Klimavicz, JS
Deeks, SG
Kovacs, JA
Ragheb, JA
AF Burbelo, Peter D.
Klimavicz, James S.
Deeks, Steve G.
Kovacs, Joseph A.
Ragheb, Jack A.
TI Lack of Evidence for Molecular Mimicry in HIV-Infected Subjects
SO PLOS ONE
LA English
DT Article
ID LUCIFERASE IMMUNOPRECIPITATION SYSTEMS; COMMON IMMUNOLOGICAL EPITOPE;
ANTIERYTHROPOIETIN ANTIBODIES; POSITIVE INDIVIDUALS; AUTOIMMUNE-DISEASE;
AUTOANTIBODIES; IMMUNODEFICIENCY; ANEMIA; QUANTIFICATION; ERYTHROPOIETIN
AB Previous studies in HIV patients have reported autoantibodies to several human proteins, including erythropoietin (EPO), interferon-alpha (IFN-alpha), interleukin-2 (IL-2), and HLA-DR, as potential mediators of anemia or immunosuppression. The etiology of these autoantibodies has been attributed to molecular mimicry between HIV epitopes and self-proteins. Here, the Luciferase Immunoprecipitation System (LIPS) was used to investigate the presence of such autoantibodies in HIV-infected adults. High levels of antibodies to HIV proteins such as capsid (p24), matrix (p17), envelope (gp41), and reverse transcriptase (RT) were detected using LIPS in both untreated and anti-retroviral-treated HIV-infected individuals but not in uninfected controls. LIPS readily detected anti-EPO autoantibodies in serum samples from subjects with presumptive pure red cell aplasia but not in any of the samples from HIV-infected or uninfected individuals. Similarly, subjects with HIV lacked autoantibodies to IFN-alpha, IL-2, HLA-DR and the immunoglobulin lambda light chain; all purported targets of molecular mimicry. While molecular mimicry between pathogen proteins and self-proteins is a commonly proposed mechanism for autoantibody production, the findings presented here indicate such a process is not common in HIV disease.
C1 [Burbelo, Peter D.; Klimavicz, James S.] Natl Inst Dent & Craniofacial Res, Dent Clin Res Core, NIH, Bethesda, MD 20892 USA.
[Deeks, Steve G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Kovacs, Joseph A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Ragheb, Jack A.] US FDA, Off Biol Prod, OPQ, CDER, Silver Spring, MD USA.
RP Burbelo, PD (reprint author), Natl Inst Dent & Craniofacial Res, Dent Clin Res Core, NIH, Bethesda, MD 20892 USA.
EM burbelop@nidcr.nih.gov
FU Divisions of Intramural Research, National Institute of Dental and
Craniofacial Research; NIH Clinical Center; CDER, Food and Drug
Administration, Foundation for AIDS Research (amFAR); Delaney AIDS
Research Enterprise (DARE) [U19AI096109]; UCSF/Gladstone Institute of
Virology & Immunology CFAR [P30 AI027763]
FX This work was supported by the Divisions of Intramural Research,
National Institute of Dental and Craniofacial Research, the NIH Clinical
Center, and the CDER, Food and Drug Administration, Foundation for AIDS
Research (amFAR), the Delaney AIDS Research Enterprise (DARE,
U19AI096109), the UCSF/Gladstone Institute of Virology & Immunology CFAR
(P30 AI027763). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 29
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U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 23
PY 2015
VL 10
IS 11
AR e0127662
DI 10.1371/journal.pone.0127662
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CX7AW
UT WOS:000365853900001
PM 26599070
ER
PT J
AU Lei, HY
Li, TW
Li, BJ
Tsai, S
Biggar, RJ
Nkrumah, F
Neequaye, J
Gutierrez, M
Epelman, S
Mbulaiteye, SM
Bhatia, K
Lo, SC
AF Lei, Haiyan
Li, Tianwei
Li, Bingjie
Tsai, Shien
Biggar, Robert J.
Nkrumah, Francis
Neequaye, Janet
Gutierrez, Marina
Epelman, Sidnei
Mbulaiteye, Sam M.
Bhatia, Kishor
Lo, Shyh-Ching
TI Epstein-Barr virus from Burkitt Lymphoma biopsies from Africa and South
America share novel LMP-1 promoter and gene variations
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MEMBRANE PROTEIN-1 GENE; NUCLEAR ANTIGEN 1; V-VAL SUBTYPE;
NASOPHARYNGEAL CARCINOMA; PERIPHERAL-BLOOD; MOLECULAR EPIDEMIOLOGY;
SEQUENCE-ANALYSIS; EBV; GENOME; TUMOR
AB Epstein Barr virus (EBV) sequence variation is thought to contribute to Burkitt lymphoma (BL), but lack of data from primary BL tumors hampers efforts to test this hypothesis. We directly sequenced EBV from 12 BL biopsies from Ghana, Brazil, and Argentina, aligned the obtained reads to the wildtype (WT) EBV reference sequence, and compared them with 100 published EBV genomes from normal and diseased people from around the world. The 12 BL EBVs were Type 1. Eleven clustered close to each other and to EBV from Raji BL cell line, but away from 12 EBVs reported from other BL-derived cell lines and away from EBV from NPC and healthy people from Asia. We discovered 23 shared novel nucleotide-base changes in the latent membrane protein (LMP)-1 promoter and gene (associated with 9 novel amino acid changes in the LMP-1 protein) of the 11 BL EBVs. Alignment of this region for the 112 EBV genomes revealed four distinct patterns, tentatively termed patterns A to D. The distribution of BL EBVs was 48%, 8%, 24% and 20% for patterns A to D, respectively; the NPC EBV's were Pattern B, and EBV-WT was pattern D. Further work is needed to investigate the association between EBV LMP-1 patterns with BL.
C1 [Lei, Haiyan; Li, Tianwei; Li, Bingjie; Tsai, Shien; Lo, Shyh-Ching] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
[Biggar, Robert J.] NCI, Bethesda, MD 20892 USA.
[Nkrumah, Francis] Noguchi Mem Inst, Accra, Ghana.
[Neequaye, Janet] Univ Ghana, Dept Child Hlth, Accra, Ghana.
[Gutierrez, Marina] Lab Stamboulian, Buenos Aires, DF, Argentina.
[Epelman, Sidnei] St Marcelina Hosp, Dept Pediat Oncol, Sao Paulo, Brazil.
[Mbulaiteye, Sam M.; Bhatia, Kishor] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA.
RP Mbulaiteye, SM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA.
EM mbulaits@mail.nih.gov; ShyhChing.Lo@fda.hhs.gov
FU Intramural Research Program of Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health,
Department of Health and Human Services [N01-CO-12400]; Food and Drug
Administration in-house Modernizing Science Fund
FX We would like to thank Dr. James J. Goedert and Charles Rabkin at the
Infections and Immunoepidemiology Branch at the National Cancer
Institute (Bethesda, Maryland) for editorial comments. We thank Drs.
Hsiao-Mei Liao and Pengfei Guo at the Center for Biologics Evaluation
and Research, Food and Drug Administration (Silver Spring, Maryland) for
preparing the final Figures and Tables for publication. Support: The
study was funded in part by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health, Department of Health and Human Services;
Grant number: N01-CO-12400, and in part by a Food and Drug
Administration in-house Modernizing Science Fund. This study utilized
the high-performance computational capabilities of the Biowulf Linux
cluster at the National Institutes of Health, Bethesda, MD
(http://biowulf.nih.gov).
NR 47
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Z9 2
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD NOV 23
PY 2015
VL 5
AR 16706
DI 10.1038/srep16706
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CW6CO
UT WOS:000365085300001
PM 26593963
ER
PT J
AU Huang, SM
AF Huang, Shiew Mei
TI CLINICAL IMPACT OF DRUG-DRUG INTERACTIONS: CONSIDERATION OF ETHNIC AND
OTHER PATIENT FACTORS
SO DRUG METABOLISM REVIEWS
LA English
DT Meeting Abstract
CT 19th North American Meeting of the
International-Society-for-the-Study-of-Xenobiotics (ISSX) / 29th Meeting
of the Japanese-Society-for-the-Study-of-Xenobiotics (JSSX)
CY OCT 19-23, 2014
CL San Francisco, CA
SP Int Soc Study Xenobiot, Japan Soc Study Xenobiot
C1 [Huang, Shiew Mei] US FDA, CDER, Off Clin Pharmacol, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 0360-2532
EI 1097-9883
J9 DRUG METAB REV
JI Drug Metab. Rev.
PD NOV 20
PY 2015
VL 47
SU 1
SI SI
MA SC1.3
BP 7
EP 7
DI 10.3109/03602532.2015.1071938
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CX3PQ
UT WOS:000365611800004
ER
PT J
AU Zhao, P
AF Zhao, Ping
TI QUANTITATIVE PREDICTIONS AND PHYSIOLOGICALLY BASED PHARMACOKINETIC
MODELING OF DRUG-DRUG INTERACTIONS BASED ON RETROSPECTIVE LITERATURE
DATA
SO DRUG METABOLISM REVIEWS
LA English
DT Meeting Abstract
CT 19th North American Meeting of the
International-Society-for-the-Study-of-Xenobiotics (ISSX) / 29th Meeting
of the Japanese-Society-for-the-Study-of-Xenobiotics (JSSX)
CY OCT 19-23, 2014
CL San Francisco, CA
SP Int Soc Study Xenobiot, Japan Soc Study Xenobiot
C1 [Zhao, Ping] US FDA, Off Clin Pharmacol, CDER, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 0360-2532
EI 1097-9883
J9 DRUG METAB REV
JI Drug Metab. Rev.
PD NOV 20
PY 2015
VL 47
SU 1
SI SI
MA SC4.1
BP 9
EP 9
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CX3PQ
UT WOS:000365611800010
ER
PT J
AU Yeung, CK
Kusama, M
Zhang, HX
Ragueneau-Majlessi, I
Argon, S
Li, L
Chang, P
Zhao, P
Zhang, L
Yoshida, K
Zineh, I
Sugiyama, Y
Huang, SM
AF Yeung, Catherine K.
Kusama, Makiko
Zhang, Huixia
Ragueneau-Majlessi, Isabelle
Argon, Sophie
Li, Li
Chang, Peter
Zhao, Ping
Zhang, Lei
Yoshida, Kenta
Zineh, Issam
Sugiyama, Yuichi
Huang, Shiew Mei
TI ASSESSMENT OF THE IMPACT OF RENAL OR HEPATIC IMPAIRMENT VS.
PHARMACOLOGIC INHIBTION ON SYSTEMIC EXPOSURE OF DRUGS
SO DRUG METABOLISM REVIEWS
LA English
DT Meeting Abstract
CT 19th North American Meeting of the
International-Society-for-the-Study-of-Xenobiotics (ISSX) / 29th Meeting
of the Japanese-Society-for-the-Study-of-Xenobiotics (JSSX)
CY OCT 19-23, 2014
CL San Francisco, CA
SP Int Soc Study Xenobiot, Japan Soc Study Xenobiot
C1 [Yeung, Catherine K.] Univ Washington, Dept Pharm, Seattle, WA 98195 USA.
[Kusama, Makiko; Sugiyama, Yuichi] Univ Tokyo, Grad Sch Pharmaceut Sci, Lab Pharmaceut Regulatory Sci, Tokyo, Japan.
[Zhang, Huixia; Li, Li; Chang, Peter; Zhao, Ping; Zhang, Lei; Yoshida, Kenta; Zineh, Issam; Huang, Shiew Mei] US FDA, Off Clin Pharmacol, CDER, Silver Spring, MD USA.
[Ragueneau-Majlessi, Isabelle; Argon, Sophie] Univ Washington, Dept Pharmaceut, Drug Interact Database Program, Seattle, WA 98195 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 0360-2532
EI 1097-9883
J9 DRUG METAB REV
JI Drug Metab. Rev.
PD NOV 20
PY 2015
VL 47
SU 1
SI SI
MA P94
BP 83
EP 84
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CX3PQ
UT WOS:000365611800168
ER
PT J
AU He, K
Zhang, J
Cai, LN
Yang, MA
Shi, Q
Tong, WD
AF He, Kan
Zhang, Jie
Cai, Lining
Yang, Mary Ann
Shi, Qin
Tong, Weida
TI POTENT INHIBITION OF BILE SALT EXPORT PUMP (BSEP) BY ERYTHROMYCIN
ESTOLATE ATTRIBUTED TO DODECYL SULFATE
SO DRUG METABOLISM REVIEWS
LA English
DT Meeting Abstract
CT 19th North American Meeting of the
International-Society-for-the-Study-of-Xenobiotics (ISSX) / 29th Meeting
of the Japanese-Society-for-the-Study-of-Xenobiotics (JSSX)
CY OCT 19-23, 2014
CL San Francisco, CA
SP Int Soc Study Xenobiot, Japan Soc Study Xenobiot
C1 [He, Kan; Cai, Lining; Yang, Mary Ann; Shi, Qin] Biotranex, Monmouth Jct, NJ USA.
[Zhang, Jie; Tong, Weida] NCTR FDA, Div Bioinformat & Biostat, Jefferson, AR USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 0360-2532
EI 1097-9883
J9 DRUG METAB REV
JI Drug Metab. Rev.
PD NOV 20
PY 2015
VL 47
SU 1
SI SI
MA P457
BP 255
EP 255
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CX3PQ
UT WOS:000365611800505
ER
PT J
AU Kim, T
Lurie, P
Pazdur, R
AF Kim, Tamy
Lurie, Peter
Pazdur, Richard
TI US Food and Drug Administration Efforts to Facilitate the Use of
Expanded Access Programs
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
C1 [Kim, Tamy; Lurie, Peter; Pazdur, Richard] US FDA, Silver Spring, MD 20993 USA.
RP Kim, T (reprint author), US FDA, Silver Spring, MD 20993 USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD NOV 20
PY 2015
VL 33
IS 33
BP 3979
EP +
DI 10.1200/JCO.2015.63.4139
PG 2
WC Oncology
SC Oncology
GA CX9JB
UT WOS:000366020600029
PM 26282656
ER
PT J
AU Wang, SJ
Bretz, F
Dmitrienko, A
Hsu, J
Hung, HMJ
Koch, G
Maurer, W
Offen, W
O'Neill, R
AF Wang, Sue-Jane
Bretz, Frank
Dmitrienko, Alex
Hsu, Jason
Hung, H. M. James
Koch, Gary
Maurer, Willi
Offen, Walt
O'Neill, Robert
TI Multiplicity in confirmatory clinical trials: a case study with
discussion from a JSM panel
SO STATISTICS IN MEDICINE
LA English
DT Article
DE accelerated approval; biomarker endpoint; decision theoretic;
multiplicity in regions; primary and key secondary endpoints
ID FAMILYWISE ERROR RATE; END-POINTS; TESTING PROCEDURES; SUBGROUPS;
ISSUES; EVENT
AB An invited panel session was conducted in the 2012 Joint Statistical Meetings, San Diego, California, USA, to stimulate the discussion on multiplicity issues in confirmatory clinical trials for drug development. A total of 11 expert panel members were invited and 9 participated. Prior to the session, a case study was previously provided to the panel members to facilitate the discussion, focusing on the key components of the study design and multiplicity. The Phase 3 development program for this new experimental treatment was based on a single randomized controlled trial alone. Each panelist was asked to clarify if he or she responded as if he or she were a pharmaceutical drug sponsor, an academic panelist or a health regulatory scientist. Copyright (c) 2015 John Wiley & Sons, Ltd.
C1 [Wang, Sue-Jane; Hung, H. M. James; O'Neill, Robert] US FDA, Silver Spring, MD 20993 USA.
[Bretz, Frank; Maurer, Willi] Novartis, Basel, Switzerland.
[Dmitrienko, Alex] Quintiles, Durham, NC USA.
[Hsu, Jason] Ohio State Univ, Columbus, OH 43210 USA.
[Koch, Gary] Univ N Carolina, Chapel Hill, NC 27515 USA.
[Offen, Walt] AbbVie, N Chicago, IL USA.
RP Wang, SJ (reprint author), US FDA, Off Biostat, OTS, CDER, Mailstop WO 21,Room 3562 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM suejane.wang@fda.hhs.gov
NR 38
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD NOV 20
PY 2015
VL 34
IS 26
BP 3461
EP 3480
DI 10.1002/sim.6561
PG 20
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA CT0RA
UT WOS:000362502800006
PM 26112381
ER
PT J
AU Laschinger, JC
Wu, CF
Ibrahim, NG
Shuren, JE
AF Laschinger, John C.
Wu, Changfu
Ibrahim, Nicole G.
Shuren, Jeffrey E.
TI Reduced Leaflet Motion in Bioprosthetic Aortic Valves - The FDA
Perspective
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID SURVEILLANCE; REGISTRY
C1 [Laschinger, John C.; Wu, Changfu; Ibrahim, Nicole G.; Shuren, Jeffrey E.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
RP Laschinger, JC (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
NR 3
TC 3
Z9 3
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD NOV 19
PY 2015
VL 373
IS 21
BP 1996
EP 1998
DI 10.1056/NEJMp1512264
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA CW4JN
UT WOS:000364957700003
PM 26437127
ER
PT J
AU Kontson, KL
Megjhani, M
Brantley, JA
Cruz-Garza, JG
Nakagome, S
Robleto, D
White, M
Civillico, E
Contreras-Vidal, JL
AF Kontson, Kimberly L.
Megjhani, Murad
Brantley, Justin A.
Cruz-Garza, Jesus G.
Nakagome, Sho
Robleto, Dario
White, Michelle
Civillico, Eugene
Contreras-Vidal, Jose L.
TI Your Brain on Art: Emergent Cortical Dynamics During Aesthetic
Experiences
SO FRONTIERS IN HUMAN NEUROSCIENCE
LA English
DT Article
DE EEG; machine learning; functional connectivity (FC); aesthetics; freely
moving
ID HIGH-FREQUENCY OSCILLATIONS; ORBITOFRONTAL CORTEX; GAMMA OSCILLATIONS;
DECISION-MAKING; EEG; SYNCHRONIZATION; APPRECIATION; POTENTIALS;
NETWORKS; DELTA
AB The brain response to conceptual art was studied with mobile electroencephalography (EEG) to examine the neural basis of aesthetic experiences. In contrast to most studies of perceptual phenomena, participants were moving and thinking freely as they viewed the exhibit The Boundary of Life is Quietly Crossed by Dario Robleto at the Menil Collection-Houston. The brain activity of over 400 subjects was recorded using dry electrode and one reference gel based EEG systems over a period of 3 months. Here, we report initial findings based on the reference system. EEG segments corresponding to each art piece were grouped into one of three classes (complex, moderate, and baseline) based on analysis of a digital image of each piece. Time, frequency, and wavelet features extracted from EEG were used to classify patterns associated with viewing art, and ranked based on their relevance for classification. The maximum classification accuracy was 55% (chance = 33%) with delta and gamma features the most relevant for classification. Functional analysis revealed a significant increase in connection strength in localized brain networks while subjects viewed the most aesthetically pleasing art compared to viewing a blank wall. The direction of signal flow showed early recruitment of broad posterior areas followed by focal anterior activation. Significant differences in the strength of connections were also observed across age and gender. This work provides evidence that EEG, deployed on freely behaving subjects, can detect selective signal flow in neural networks, identify significant differences between subject groups, and report with greater-than-chance accuracy the complexity of a subject's visual percept of aesthetically pleasing art. Our approach, which allows acquisition of neural activity "in action and context," could lead to understanding of how the brain integrates sensory input and its ongoing internal state to produce the phenomenon which we term aesthetic experience.
C1 [Kontson, Kimberly L.; Civillico, Eugene] US FDA, Ctr Devices & Radiol Hlth, Div Biomed Phys, Off Sci & Engn Labs, Silver Spring, MD 20993 USA.
[Kontson, Kimberly L.; Megjhani, Murad; Brantley, Justin A.; Cruz-Garza, Jesus G.; Nakagome, Sho; Contreras-Vidal, Jose L.] Univ Houston, Dept Elect & Comp Engn, Lab Noninvas Brain Machine Interfaces, Houston, TX USA.
[Robleto, Dario] American Artist, Houston, TX USA.
[Robleto, Dario; White, Michelle] Menil Collect, Houston, TX USA.
RP Kontson, KL (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Biomed Phys, Off Sci & Engn Labs, Silver Spring, MD 20993 USA.
EM kimberly.kontson@fda.hhs.gov
OI KONTSON, KIMBERLY/0000-0002-4978-6011
FU Cullen College of Engineering at the University of Houston; National
Science Foundation Awards [1219321, 1302339]; NSF NCS-FO Award [1533691]
FX The authors would like to graciously thank Jesus Tamez-Duque and
Fernando Martinez-Garcia from Tecnologico de Monterrey for providing the
US ELM code used to perform clustering analysis and for their
contributions to the explanation of the algorithm, as well as all the
members from the Laboratory for Non-Invasive Brain Machine Interfaces at
the University of Houston for their assistance in acquiring data at the
museum. This work was partially supported by a cross-cutting seed grant
from the Cullen College of Engineering at the University of Houston and
National Science Foundation Awards 1219321 and 1302339. This work has
also been supported in part by NSF NCS-FO Award 1533691.
NR 69
TC 4
Z9 4
U1 5
U2 14
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-5161
J9 FRONT HUM NEUROSCI
JI Front. Hum. Neurosci.
PD NOV 18
PY 2015
VL 9
AR 626
DI 10.3389/fnhum.2015.00626
PG 17
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA CY7BK
UT WOS:000366562600001
PM 26635579
ER
PT J
AU Shalabi, H
Angiolillo, A
Vezina, G
Rubenstein, JL
Pittaluga, S
Raffeld, M
Marcus, L
AF Shalabi, Haneen
Angiolillo, Anne
Vezina, Gilbert
Rubenstein, James L.
Pittaluga, Stefania
Raffeld, Mark
Marcus, Leigh
TI Prolonged Complete Response in a Pediatric Patient With Primary
Peripheral T-Cell Lymphoma of the Central Nervous System
SO PEDIATRIC HEMATOLOGY AND ONCOLOGY
LA English
DT Article
DE CNS tumors; NHL; therapy
ID PRIMARY-CNS-LYMPHOMA; DESCRIPTIVE ANALYSIS; COLLABORATIVE-GROUP;
GAMMA-DELTA; ADOLESCENTS; CHILDREN; ORIGIN
AB We describe a child with a 2-week history of progressive headaches, blurry vision, and intermittent vomiting. Magnetic resonance imaging (MRI) of the brain showed a deep left hemispheric lesion with extension into the corpus callosum. Histology and immunophenotyping of the lesion was consistent with peripheral T-cell lymphoma, not otherwise specified. Chemotherapy was initiated and a complete remission was achieved. This case illustrates that a chemotherapeutic regimen used in adults with central nervous system (CNS) lymphoma can achieve durable remissions in pediatric patients with peripheral T-cell lymphoma, not otherwise specified of the CNS.
C1 [Shalabi, Haneen; Angiolillo, Anne] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Div Pediat Hematol & Oncol, Washington, DC 20010 USA.
[Vezina, Gilbert] Childrens Natl Med Ctr, Dept Radiol, Washington, DC 20010 USA.
[Rubenstein, James L.] Univ Calif San Francisco, Div Hematol & Oncol, San Francisco, CA 94143 USA.
[Pittaluga, Stefania; Raffeld, Mark] NIH, Pathol Lab, Bethesda, MD 20892 USA.
[Marcus, Leigh] Food & Drug Adm, Silver Spring, MD USA.
RP Shalabi, H (reprint author), Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Div Pediat Hematol & Oncol, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM hshalabi@childrensnational.org
FU NCI NIH HHS [R01 CA139083, R21 CA184694]
NR 18
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0888-0018
EI 1521-0669
J9 PEDIATR HEMAT ONCOL
JI Pediatr. Hematol. Oncol.
PD NOV 17
PY 2015
VL 32
IS 8
BP 529
EP 534
DI 10.3109/08880018.2015.1074325
PG 6
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CZ2EC
UT WOS:000366916900004
PM 26384083
ER
PT J
AU Wang, CL
Graham, DJ
Kane, RC
Xie, DQ
Wernecke, M
Levenson, M
MaCurdy, TE
Houstoun, M
Ryan, Q
Wong, S
Mott, K
Sheu, TC
Limb, S
Worrall, C
Kelman, JA
Reichman, ME
AF Wang, Cunlin
Graham, David J.
Kane, Robert C.
Xie, Diqiong
Wernecke, Michael
Levenson, Mark
MaCurdy, Thomas E.
Houstoun, Monica
Ryan, Qin
Wong, Sarah
Mott, Katrina
Sheu, Ting-Chang
Limb, Susan
Worrall, Chris
Kelman, Jeffrey A.
Reichman, Marsha E.
TI Comparative Risk of Anaphylactic Reactions Associated With Intravenous
Iron Products
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID FERRIC GLUCONATE COMPLEX; ADVERSE DRUG EVENTS; HEMODIALYSIS-PATIENTS;
PARENTERAL IRON; SYSTEMATIC ANALYSIS; DEXTRAN; SAFETY; ANEMIA; THERAPY;
SUCROSE
AB IMPORTANCE All intravenous (IV) iron products are associated with anaphylaxis, but the comparative safety of each product has not been well established.
OBJECTIVE To compare the risk of anaphylaxis among marketed IV iron products.
DESIGN, SETTING, AND PARTICIPANTS Retrospective new user cohort study of IV iron recipients (n = 688 183) enrolled in the US fee-for-service Medicare program from January 2003 to December 2013. Analyses involving ferumoxytol were limited to the period January 2010 to December 2013.
EXPOSURES Administrations of IV iron dextran, gluconate, sucrose, or ferumoxytol as reported in outpatient Medicare claims data.
MAIN OUTCOMES AND MEASURES Anaphylaxiswas identified using a prespecified and validated algorithm defined with standard diagnosis and procedure codes and applied to both inpatient and outpatient Medicare claims. The absolute and relative risks of anaphylaxis were estimated, adjusting for imbalances among treatment groups.
RESULTS A total of 274 anaphylaxis cases were identified at first exposure, with an additional 170 incident anaphylaxis cases identified during subsequent IV iron administrations. The risk for anaphylaxis at first exposure was 68 per 100 000 persons for iron dextran (95% CI, 57.8-78.7 per 100 000) and 24 per 100 000 persons for all nondextran IV iron products combined (iron sucrose, gluconate, and ferumoxytol) (95% CI, 20.0-29.5 per 100 000), with an adjusted odds ratio (OR) of 2.6 (95% CI, 2.0-3.3; P <.001). At first exposure, when compared with iron sucrose, the adjusted OR of anaphylaxis for iron dextran was 3.6 (95% CI, 2.4-5.4); for iron gluconate, 2.0 (95% CI 1.2, 3.5); and for ferumoxytol, 2.2 (95% CI, 1.1-4.3). The estimated cumulative anaphylaxis risk following total iron repletion of 1000mg administered within a 12-week period was highest with iron dextran (82 per 100 000 persons, 95% CI, 70.5-93.1) and lowest with iron sucrose (21 per 100 000 persons, 95% CI, 15.3-26.4).
CONCLUSIONS AND RELEVANCE Among patients in the US Medicare nondialysis population with first exposure to IV iron, the risk of anaphylaxis was highest for iron dextran and lowest for iron sucrose.
C1 [Wang, Cunlin; Graham, David J.; Mott, Katrina; Reichman, Marsha E.] US FDA, Div Epidemiol 1, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA.
[Kane, Robert C.; Houstoun, Monica; Ryan, Qin; Limb, Susan] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA.
[Xie, Diqiong; Levenson, Mark] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA.
[Wernecke, Michael; MaCurdy, Thomas E.; Wong, Sarah; Sheu, Ting-Chang] Acumen LLC, Burlingame, CA USA.
[Mott, Katrina] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Limb, Susan] Genentech Inc, San Francisco, CA 94080 USA.
[Worrall, Chris; Kelman, Jeffrey A.] Ctr Medicare & Medicaid Serv, Washington, DC USA.
RP Wang, CL (reprint author), US FDA, Div Epidemiol 1, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA.
EM cunlin.wang@fda.hhs.gov
FU Centers for Medicare & Medicaid Services; US Food and Drug
Administration
FX This study was funded through an intraagency agreement between the
Centers for Medicare & Medicaid Services and the US Food and Drug
Administration.
NR 26
TC 26
Z9 26
U1 2
U2 9
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD NOV 17
PY 2015
VL 314
IS 19
BP 2062
EP 2068
DI 10.1001/jama.2015.15572
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA CW1PR
UT WOS:000364764200021
PM 26575062
ER
PT J
AU Frasch, CE
Kapre, SV
Lee, CH
Preaud, JM
AF Frasch, Carl E.
Kapre, Subhash V.
Lee, Che-Hung
Preaud, Jean-Marie
TI Technical Development of a New Meningococcal Conjugate Vaccine
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE meningococcal; conjugate vaccine; group A; MenAfriVac; African
meningitis belt
ID TETANUS TOXOID CONJUGATE; GROUP-A; NEISSERIA-MENINGITIDIS;
POLYSACCHARIDE; AFRICA; IMMUNOGENICITY; ACTIVATION; PRODUCT
AB Background. Group A Neisseria meningitidis has been a major cause of bacterial meningitis in the sub-Saharan region of Africa in the meningitis belt. Neisseria meningitidis is an encapsulated pathogen, and antibodies against the capsular polysaccharide are protective. Polysaccharide-protein conjugate vaccines have proven to be highly effective against several different encapsulated bacterial pathogens. Purified polysaccharide vaccines have been used to control group A meningococcal (MenA) epidemics with minimal success.
Methods. A monovalent MenA polysaccharide-tetanus toxoid conjugate was therefore developed. This vaccine was developed by scientists working with the Meningitis Vaccine Project, a partnership between PATH and the World Health Organization.
Results. A high-efficiency conjugation method was developed in the Laboratory of Bacterial Polysaccharides in the Center for Biologics Evaluation and Research and transferred to the Serum Institute of India, Ltd, which then developed methods for purification of the group A polysaccharide and used its tetanus toxoid as the carrier protein to produce the now-licensed, highly effective MenAfriVac conjugate vaccine.
Conclusions.Although many years of application of meningococcal polysaccharide vaccines have had minimal success in preventing meningococcal epidemics in the meningitis belt of Africa, our collaborative efforts to develop a MenA conjugate vaccine yielded a safe and highly effective vaccine.
C1 [Frasch, Carl E.] Frasch Biol Consulting, Martinsburg, WV 25402 USA.
[Kapre, Subhash V.] Serum Inst India Ltd, Pune, Maharashtra, India.
[Lee, Che-Hung] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
[Preaud, Jean-Marie] PATH, Meningitis Vaccine Project, Ferney Voltaire, France.
RP Frasch, CE (reprint author), Frasch Biol Consulting, POB 986, Martinsburg, WV 25402 USA.
EM cfrasch1@juno.com
FU Meningitis Vaccine Project from Bill & Melinda Gates Foundation
FX This article appears as part of the supplement "The Meningitis Vaccine
Project: The Development, Licensure, Introduction, and Impact of a New
Group A Meningococcal Conjugate Vaccine for Africa," sponsored by the
Meningitis Vaccine Project through a grant from the Bill & Melinda Gates
Foundation.
NR 30
TC 1
Z9 1
U1 1
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD NOV 15
PY 2015
VL 61
SU 5
BP S404
EP S409
DI 10.1093/cid/civ595
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CW7FF
UT WOS:000365162700005
PM 26553667
ER
PT J
AU Price, GA
Hollander, AM
Plikaytis, BD
Mocca, BT
Carlone, G
Findlow, H
Borrow, R
Sow, SO
Diallo, A
Idoko, OT
Enwere, GC
Elie, C
Preziosi, MP
Kulkarni, PS
Bash, MC
AF Price, Gregory A.
Hollander, Aimee M.
Plikaytis, Brian D.
Mocca, Brian T.
Carlone, George
Findlow, Helen
Borrow, Ray
Sow, Samba O.
Diallo, Aldiouma
Idoko, Olubukola T.
Enwere, Godwin C.
Elie, Cheryl
Preziosi, Marie-Pierre
Kulkarni, Prasad S.
Bash, Margaret C.
TI Human Complement Bactericidal Responses to a Group A Meningococcal
Conjugate Vaccine in Africans and Comparison to Responses Measured by 2
Other Group A Immunoassays
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE MenAfriVac; bactericidal activity; assay development; Neisseria
meningitidis; clinical trials
ID NEISSERIA-MENINGITIDIS SEROGROUP; POLYSACCHARIDE VACCINE; ANTIBODY
PERSISTENCE; HUMAN IMMUNITY; SERUM; SAFETY; IMMUNOGENICITY; CARRIAGE;
DISEASE; EPIDEMIC
AB Background. PsA-TT (MenAfriVac) is a conjugated polysaccharide vaccine developed to eliminate group A meningococcal disease in Africa. Vaccination of African study participants with 1 dose of PsA-TT led to the production of anti-A polysaccharide antibodies and increased serum bactericidal activity measured using rabbit complement (rSBA). Bactericidal responses measured with human complement (hSBA) are presented here.
Methods. Sera collected before and at 28 days and 1 year after vaccination with either PsA-TT or quadrivalent polysaccharide vaccine (PsACWY) from a random, age-distributed 360-subject subset of the Meningitis Vaccine Project study of PsA-TT in Africans aged 2-29 years were tested for hSBA. Geometric mean titer, fold-rise, and threshold analyses were compared between vaccine groups and age groups. hSBA, rSBA, and immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) results were compared and assay correlation and agreement determined.
Results. hSBA responses to PsA-TT were substantially higher than those to PsACWY at 28 days and 1 year following immunization, similar to previously reported rSBA and IgG results. The hSBA and IgG ELISA results identified differences between age groups that were not evident by rSBA. The rSBA data indicated sustained high titers 1 year after immunization, whereas hSBA GMTs at 1 year approached 4 in young children.
Conclusions. The high level of protection following PsA-TT immunization campaigns is consistent with the strong hSBA immune responses observed here. Future implementation decisions will likely depend on immunologic data and their long-term correlation with disease and carriage prevention. Expanded immunologic and epidemiologic surveillance may improve the interpretation of differences between these immunoassays.
C1 [Price, Gregory A.; Hollander, Aimee M.; Mocca, Brian T.; Bash, Margaret C.] US FDA, Lab Bacterial Polysaccharides, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
[Plikaytis, Brian D.; Carlone, George; Elie, Cheryl] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Findlow, Helen; Borrow, Ray] Manchester Royal Infirm, Vaccine Evaluat Unit, Publ Hlth England, Manchester, Lancs, England.
[Sow, Samba O.] Minist Sante, Ctr Dev Vaccins, Bamako, Mali.
[Diallo, Aldiouma] Inst Rech Dev, Niakhar, Senegal.
[Idoko, Olubukola T.] MRC Unit, Vaccines & Immun Theme, Basse, Gambia.
[Enwere, Godwin C.; Preziosi, Marie-Pierre] PATH, Meningitis Vaccine Project, Ferney Voltaire, France.
[Preziosi, Marie-Pierre] WHO, Meningitis Vaccine Project, Dept Immunizat Vaccines & Biol, CH-1211 Geneva, Switzerland.
[Kulkarni, Prasad S.] Serum Inst India Ltd, Pune, Maharashtra, India.
RP Bash, MC (reprint author), US FDA, Lab Bacterial Polysaccharides, DBPAP, CBER, 10903 New Hampshire Ave,Bld 52 Rm 5212, Silver Spring, MD 20993 USA.
EM margaret.bash@fda.hhs.gov
FU Meningitis Vaccine Project from Bill & Melinda Gates Foundation
FX This article appears as part of the supplement "The Meningitis Vaccine
Project: The Development, Licensure, Introduction, and Impact of a New
Group A Meningococcal Conjugate Vaccine for Africa," sponsored by the
Meningitis Vaccine Project through a grant from the Bill & Melinda Gates
Foundation.
NR 36
TC 1
Z9 1
U1 1
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD NOV 15
PY 2015
VL 61
SU 5
BP S554
EP S562
DI 10.1093/cid/civ504
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CW7FF
UT WOS:000365162700026
PM 26553688
ER
PT J
AU Alusta, P
Buzatu, D
Williams, A
Cooper, WM
Tarasenko, O
Dorey, RC
Hall, R
Parker, WR
Wilkes, JG
AF Alusta, Pierre
Buzatu, Dan
Williams, Anna
Cooper, Willie-Mae
Tarasenko, Olga
Dorey, R. Cameron
Hall, Reggie
Parker, W. Ryan
Wilkes, Jon G.
TI Instrumental improvements and sample preparations that enable
reproducible, reliable acquisition of mass spectra from whole bacterial
cells
SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY
LA English
DT Article
ID ASSISTED-LASER-DESORPTION/IONIZATION; DESORPTION-IONIZATION-TIME;
GRAM-TYPE DIFFERENTIATION; FOOD MATRIX INTERFERENCE; RAPID
IDENTIFICATION; SPECIES IDENTIFICATION; FLOW-CYTOMETRY; SPECTROMETRY;
MYCOBACTERIA; EXTRACTS
AB RationaleRapid sub-species characterization of pathogens is required for timely responses in outbreak situations. Pyrolysis mass spectrometry (PyMS) has the potential to be used for this purpose.
MethodsHowever, in order to make PyMS practical for traceback applications, certain improvements related to spectrum reproducibility and data acquisition speed were required. The main objectives of this study were to facilitate fast detection (<30min to analyze 6 samples, including preparation) and sub-species-level bacterial characterization based on pattern recognition of mass spectral fingerprints acquired from whole cells volatilized and ionized at atmospheric pressure. An AccuTOF DART mass spectrometer was re-engineered to permit ionization of low-volatility bacteria by means of Plasma Jet Ionization (PJI), in which an electric discharge, and, by extension, a plasma beam, impinges on sample cells.
ResultsInstrumental improvements and spectral acquisition methodology are described. Performance of the re-engineered system was assessed using a small challenge set comprised of assorted bacterial isolates differing in identity by varying amounts. In general, the spectral patterns obtained allowed differentiation of all samples tested, including those of the same genus and species but different serotypes.
ConclusionsFluctuations of +/- 15% in bacterial cell concentrations did not substantially compromise replicate spectra reproducibility. (c) 2015 National Center for Toxicological Research. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.
C1 [Alusta, Pierre; Buzatu, Dan; Williams, Anna; Cooper, Willie-Mae; Dorey, R. Cameron; Wilkes, Jon G.] US FDA, Natl Ctr Toxicol Res, Div Syst Biol, Innovat Safety Technol Branch, Jefferson, AR 72079 USA.
[Tarasenko, Olga] Univ Arkansas, Dept Biol, Little Rock, AR 72204 USA.
[Hall, Reggie] US FDA, Natl Ctr Toxicol Res, Bionet Corp, Jefferson, AR 72079 USA.
[Parker, W. Ryan] Univ Texas Austin, Dept Chem, Austin, TX 78712 USA.
RP Wilkes, JG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Biol, Innovat Safety Technol Branch, Bldg 26,3900 NCTR Rd, Jefferson, AR 72079 USA.
EM jon.wilkes@fda.hhs.gov
OI Parker, William/0000-0001-5753-2508
FU ORISE
FX This study conforms to the IBC protocol # 09092. The authors extend
their gratitude to ORISE for partial financial support. The opinions
expressed are those of the authors and do not necessarily reflect those
of the USFDA.
NR 38
TC 0
Z9 0
U1 4
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0951-4198
EI 1097-0231
J9 RAPID COMMUN MASS SP
JI Rapid Commun. Mass Spectrom.
PD NOV 15
PY 2015
VL 29
IS 21
BP 1961
EP 1968
DI 10.1002/rcm.7299
PG 8
WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy
SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy
GA CT2QJ
UT WOS:000362647900005
PM 26443394
ER
PT J
AU Stone, W
Grabias, B
Lanke, K
Zheng, H
Locke, E
Diallo, D
Birkett, A
Morin, M
Bousema, T
Kumar, S
AF Stone, Will
Grabias, Bryan
Lanke, Kjerstin
Zheng, Hong
Locke, Emily
Diallo, Diadier
Birkett, Ashley
Morin, Merribeth
Bousema, Teun
Kumar, Sanjai
TI A comparison of Plasmodium falciparum circumsporozoite protein-based
slot blot and ELISA immuno-assays for oocyst detection in mosquito
homogenates
SO MALARIA JOURNAL
LA English
DT Article
DE Plasmodium falciparum; Anopheles; Sporozoite; Oocyst; Circumsporozoite
protein; ELISA; Slot-blot; Immuno-assay; Mosquito infection
ID ANOPHELES-STEPHENSI; MALARIA TRANSMISSION; POPULATION-DYNAMICS;
SPOROZOITES; INFECTION; ASSAYS; GAMETOCYTES; SPOROGONY; CULICIDAE;
ANTIGEN
AB Background: The infectivity of Plasmodium gametocytes is typically determined by microscopically examining the midguts of mosquitoes that have taken a blood meal containing potentially infectious parasites. Such assessments are required for the development and evaluation of transmission-reducing interventions (TRI), but are limited by subjectivity, technical complexity and throughput. The detection of circumsporozoite protein (CSP) by enzyme-linked immunosorbent assay (ELISA) and enhanced chemiluminescent slot-blot (ECL-SB) may be used as objective, scalable alternatives to microscopy for the determination of infection prevalence.
Methods: To compare the performance of the CSP ELISA and ECL-SB for the detection of mosquito infection, four groups of Anopheles stephensi mosquitoes were infected with cultured Plasmodium falciparum gametocytes. At day-8 post-infection (PI), parasite status was determined by microscopy for a sample of mosquitoes from each group. At days 8 and 10 PI, the parasite status of separate mosquito samples was analysed by both CSP ELISA and ECL-SB.
Results: When mosquito samples were analysed 8 days PI, the ECL-SB determined similar infection prevalence to microscopy; CSP ELISA lacked the sensitivity to detect CSP in all infected mosquitoes at this early time point. When mosquitoes were analysed 48 h later (10 days PI) both assays performed as well as microscopy for infection detection.
Conclusions: Whilst microscopical examination of mosquito guts is of great value when quantification of parasite burden is required, ECL-SB and CSP ELISA are suitable alternatives at day 10 PI when infection prevalence is the desired endpoint, although CSP ELISA is not suitable at day 8 PI. These results are important to groups considering large-scale implementation of TRI.
C1 [Stone, Will; Lanke, Kjerstin; Bousema, Teun] Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, NL-6525 ED Nijmegen, Netherlands.
[Grabias, Bryan; Zheng, Hong; Kumar, Sanjai] US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review,Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
[Locke, Emily; Diallo, Diadier; Birkett, Ashley; Morin, Merribeth] PATH Malaria Vaccine Initiat, Washington, DC USA.
[Bousema, Teun] London Sch Hyg & Trop Med, Dept Immunol & Infect, London WC1, England.
RP Bousema, T (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, NL-6525 ED Nijmegen, Netherlands.
EM teun.bousema@radboudumc.nl
RI Stone, Will/F-9416-2016; Bousema, Teun/N-3574-2014
FU PATH Malaria Vaccine Initiative (MVI); Marie Curie Career Integration
Grant from the European Community's Seventh Framework Programme (SIGNAL)
[PCIG-GA-2012-333936]; PATH-Malaria Vaccine Initiative
FX We would like to thank Jacqueline Kuhnen, Laura Pelser-Posthumus, Astrid
Pouwelsen, and Jolanda Klaassen for conducting all mosquito breeding and
for their assistance in the evaluation of mosquito membrane-feeding
experiments. WS and TB are supported by the PATH Malaria Vaccine
Initiative (MVI) and by a Marie Curie Career Integration Grant from the
European Community's Seventh Framework Programme (SIGNAL,
PCIG-GA-2012-333936). SK was in part funded by a research grant from the
PATH-Malaria Vaccine Initiative.
NR 42
TC 0
Z9 0
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD NOV 14
PY 2015
VL 14
AR 451
DI 10.1186/s12936-015-0954-2
PG 9
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA CW1NV
UT WOS:000364758200001
PM 26573271
ER
PT J
AU Kassa, T
Jana, S
Strader, MB
Meng, FT
Jia, YP
Wilson, MT
Alayash, AI
AF Kassa, Tigist
Jana, Sirsendu
Strader, Michael Brad
Meng, Fantao
Jia, Yiping
Wilson, Michael T.
Alayash, Abdu I.
TI Sickle Cell Hemoglobin in the Ferryl State Promotes beta Cys-93
Oxidation and Mitochondrial Dysfunction in Epithelial Lung Cells (E10)
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SPERM-WHALE MYOGLOBIN; ACUTE CHEST SYNDROME; HYDROGEN-PEROXIDE; HEME
OXYGENASE-1; MASS-SPECTROMETRY; BLOOD SUBSTITUTES; CROSS-LINKING;
HAPTOGLOBIN; STRESS; DISEASE
AB Polymerization of intraerythrocytic deoxyhemoglobin S (HbS) is the primary molecular event that leads to hemolytic anemia in sickle cell disease (SCD). We reasoned that HbS may contribute to the complex pathophysiology of SCD in part due to its pseudoperoxidase activity. We compared oxidation reactions and the turnover of oxidation intermediates of purified human HbS and HbA. Hydrogen peroxide (H2O2) drives a catalytic cycle that includes the following three distinct steps: 1) initial oxidation of ferrous (oxy) to ferryl Hb; 2) autoreduction of the ferryl intermediate to ferric (metHb); and 3) reaction of metHb with an additional H2O2 molecule to regenerate the ferryl intermediate. Ferrous and ferric forms of both proteins underwent initial oxidation to the ferryl heme in the presence of H2O2 at equal rates. However, the rate of autoreduction of ferryl to the ferric form was slower in the HbS solutions. Using quantitative mass spectrometry and the spin trap, 5,5-dimethyl-1pyrroline-N-oxide, we found more irreversibly oxidized beta Cys-93 in HbS than in HbA. Incubation of the ferric or ferryl HbS with cultured lung epithelial cells (E10) induced a drop in mitochondrial oxygen consumption rate and impairment of cellular bioenergetics that was related to the redox state of the iron. Ferryl HbS induced a substantial drop in the mitochondrial transmembrane potential and increases in cytosolic heme oxygenase (HO-1) expression and mitochondrial colocalization in E10 cells. Thus, highly oxidizing ferryl Hb and heme, the product of oxidation, may be central to the evolution of vasculopathy in SCD and may suggest therapeutic modalities that interrupt heme-mediated inflammation.
C1 [Kassa, Tigist; Jana, Sirsendu; Strader, Michael Brad; Meng, Fantao; Jia, Yiping; Alayash, Abdu I.] Food & Drug Adm, Lab Biochem & Vasc Biol, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
[Wilson, Michael T.] Univ Essex, Dept Biol Sci, Colchester CO4 3SQ, Essex, England.
RP Alayash, AI (reprint author), Food & Drug Adm, Lab Biochem & Vasc Biol, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
EM abdu.alayash@fda.hhs.gov
FU National Institutes of Health NHLBI [P01-HL110900]; United States Food
and Drug Administration (MODSCI)
FX This work was supported by National Institutes of Health NHLBI Grant
P01-HL110900 (to A. I. A.) and grants from the United States Food and
Drug Administration (MODSCI) (to A. I. A.). The authors declare that
they have no conflicts of interest with the contents of this article.
NR 70
TC 4
Z9 4
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD NOV 13
PY 2015
VL 290
IS 46
BP 27939
EP 27958
DI 10.1074/jbc.M115.651257
PG 20
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CX5QP
UT WOS:000365757500042
PM 26396189
ER
PT J
AU Mudalige, TK
Qu, HO
Linder, SW
AF Mudalige, Thilak K.
Qu, Haiou
Linder, Sean W.
TI An improved methodology of asymmetric flow field flow fractionation
hyphenated with inductively coupled mass spectrometry for the
determination of size distribution of gold nanoparticles in dietary
supplements
SO JOURNAL OF CHROMATOGRAPHY A
LA English
DT Article
DE Nanoparticles; Dietary supplements; Asymmetric flow field flow
fractionation; Size distribution; Inductively coupled plasma mass;
spectrometry
ID LIGHT-SCATTERING DETECTION; RETENTION BEHAVIOR; SEPARATION; OPTIMIZATION
AB Engineered nanoparticles are available in large numbers of commercial products claiming various health benefits. Nanoparticle absorption, distribution, metabolism, excretion, and toxicity in a biological system are dependent on particle size, thus the determination of size and size distribution is essential for full characterization. Number based average size and size distribution is a major parameter for full characterization of the nanoparticle. In the case of polydispersed samples, large numbers of particles are needed to obtain accurate size distribution data. Herein, we report a rapid methodology, demonstrating improved nanoparticle recovery and excellent size resolution, for the characterization of gold nanoparticles in dietary supplements using asymmetric flow field flow fractionation coupled with visible absorption spectrometry and inductively coupled plasma mass spectrometry. A linear relationship between gold nanoparticle size and retention times was observed, and used for characterization of unknown samples. The particle size results from unknown samples were compared to results from traditional size analysis by transmission electron microscopy, and found to have less than a 5% deviation in size for unknown product over the size range from 7 to 30 nm. Published by Elsevier B.V.
C1 [Mudalige, Thilak K.; Qu, Haiou; Linder, Sean W.] US FDA, Arkansas Reg Lab, Off Regulatory Affairs, Jefferson, AR 72079 USA.
RP Mudalige, TK (reprint author), US FDA, Arkansas Reg Lab, Off Regulatory Affairs, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM Thilak.Mudalige@fda.hhs.gov; Sean.Linder@fda.hhs.gov
NR 28
TC 5
Z9 5
U1 2
U2 15
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0021-9673
EI 1873-3778
J9 J CHROMATOGR A
JI J. Chromatogr. A
PD NOV 13
PY 2015
VL 1420
BP 92
EP 97
DI 10.1016/j.chroma.2015.09.091
PG 6
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA CV4VO
UT WOS:000364264800010
PM 26456512
ER
PT J
AU Hu, Y
Yan, HJ
Mammel, M
Chen, HF
AF Hu, Yuan
Yan, Huijun
Mammel, Mark
Chen, Haifeng
TI Sequence-independent amplification coupled with DNA microarray analysis
for detection and genotyping of noroviruses
SO AMB EXPRESS
LA English
DT Article
DE Noroviruses; Sequence-independent amplification; DNA microarray;
Detection; Genotyping
ID NORWALK-LIKE VIRUSES; REVERSE TRANSCRIPTION-PCR; ROUND-STRUCTURED
VIRUSES; IDENTIFICATION; CLASSIFICATION; INFECTION; DIVERSITY; PRIMERS;
SYSTEM; STRAIN
AB Noroviruses (NoVs) have high levels of genetic sequence diversities, which lead to difficulties in designing robust universal primers to efficiently amplify specific viral genomes for molecular analysis. We here described the practicality of sequence-independent amplification combined with DNA microarray analysis for simultaneous detection and genotyping of human NoVs in fecal specimens. We showed that single primer isothermal linear amplification (Ribo-SPIA) of genogroup I (GI) and genogroup II (GII) NoVs could be run through the same amplification protocol without the need to design and use any virus-specific primers. Related virus could be subtyped by the unique pattern of hybridization with the amplified product to the microarray. By testing 22 clinical fecal specimens obtained from acute gastroenteritis cases as blinded samples, 2 were GI positive and 18 were GII positive as well as 2 negative for NoVs. A NoV GII positive specimen was also identified as having co-occurrence of hepatitis A virus. The study showed that there was 100 % concordance for positive NoV detection at genogroup level between the results of Ribo-SPIA/microarray and the phylogenetic analysis of viral sequences of the capsid gene. In addition, 85 % genotype agreement was observed for the new assay compared to the results of phylogenetic analysis.
C1 [Hu, Yuan] US FDA, Northeast Reg Lab, Off Regulatory Affairs, Jamaica, NY USA.
[Yan, Huijun] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Microbiol, Guangzhou 510275, Guangdong, Peoples R China.
[Mammel, Mark; Chen, Haifeng] US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA.
RP Chen, HF (reprint author), US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA.
EM haifeng.chen@fda.hhs.gov
NR 26
TC 0
Z9 0
U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2191-0855
J9 AMB EXPRESS
JI AMB Express
PD NOV 10
PY 2015
VL 5
AR 69
DI 10.1186/s13568-015-0156-x
PG 9
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA CW7DL
UT WOS:000365158100001
PM 26556029
ER
PT J
AU Rahman, Z
Korang-Yeboah, M
Siddiqui, A
Mohammad, A
Khan, MA
AF Rahman, Ziyaur
Korang-Yeboah, Maxwell
Siddiqui, Akhtar
Mohammad, Adil
Khan, Mansoor A.
TI Understanding effect of formulation and manufacturing variables on the
critical quality attributes of warfarin sodium product
SO INTERNATIONAL JOURNAL OF PHARMACEUTICS
LA English
DT Article
DE Warfarin sodium clathrate; Amorphous; Critical quality attributes;
Disintegration time; Dissolution; Crystallinity and stability
ID TABLETING PROPERTIES; LACTOSE; CONSOLIDATION; COMPACTION
AB Warfarin sodium (WS) is a narrow therapeutic index drug and its product quality should be thoroughly understood and monitored in order to avoid clinical performance issues. This study was focused on understanding the effect of manufacturing and formulation variables on WS product critical quality attributes (CQAs). Eight formulations were developed with lactose monohydrate (LM) or lactose anhydrous (LA), and were either wet granulated or directly compressed. Formulations were granulated either with ethanol, isopropyl alcohol (IPA) and IPA-water mixture (50: 50). Formulations were characterized for IPA, water content, hardness, disintegration time (DT), assay, dissolution and drug physical forms (scanning electron microscopy (SEM), near infrared chemical imaging (NIR-CI), X-ray powder diffraction (XRPD) and solid state nuclear magnetic resonance (ssNMR)), and performed accelerated stability studies at 40 degrees C/75% RH for three days. The DT and dissolution of directly compressed formulations were faster than wet granulated formulations. This was due to phase transformation of crystalline drug into its amorphous form as indicated by SEM, NIR-CI, XRPD and ssNMR data which itself act as a binder. Similarly, LM showed faster disintegration and dissolution than LA containing formulations. Stability results indicated an increase in hardness and DT, and a decrease in dissolution rate and extent. This was due to phase transformation of the drug and consolidation with particles' bonding. In conclusion, the CQAs of WS product were significantly affected by manufacturing and formulation variables. Published by Elsevier B.V.
C1 [Rahman, Ziyaur; Korang-Yeboah, Maxwell; Siddiqui, Akhtar; Mohammad, Adil; Khan, Mansoor A.] US FDA, CDER, DPQR, Silver Spring, MD 20993 USA.
RP Khan, MA (reprint author), US FDA, CDER, DPQR, LS Bldg 64,Room 1070,10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM Mansoor.Khan@fda.hhs.gov
OI Rahman, Ziyaur/0000-0002-0402-825X
FU FDAs Office of Chief Scientist
FX FDAs Office of Chief Scientist is gratefully acknowledged for the
infrastructure grant to carry out part of this work.
NR 20
TC 1
Z9 1
U1 0
U2 15
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5173
EI 1873-3476
J9 INT J PHARMACEUT
JI Int. J. Pharm.
PD NOV 10
PY 2015
VL 495
IS 1
BP 19
EP 30
DI 10.1016/j.ijpharm.2015.08.065
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CT7CE
UT WOS:000362970000003
PM 26319638
ER
PT J
AU Garner, J
Skidmore, S
Park, H
Park, K
Choi, S
Wang, Y
AF Garner, John
Skidmore, Sarah
Park, Haesun
Park, Kinam
Choi, Stephanie
Wang, Yan
TI A protocol for assay of poly(lactide-co-glycolide) in clinical products
SO INTERNATIONAL JOURNAL OF PHARMACEUTICS
LA English
DT Article
DE PLGA; Molecular weight; Lactide: glycolide ratio; End-cap; Triptorelin;
Risperidone
ID IN-VITRO DEGRADATION; MOLECULAR-WEIGHT; CONTROLLED DELIVERY;
DRUG-RELEASE; MICROPARTICLES; PLGA; MICROSPHERES; SYSTEMS; MODEL; RATES
AB Poly(lactide-co-glycolide) (PLGA) is the key component of long acting drug products responsible for providing sustained release in a controlled manner. The objective of the current study was to develop and validate an analytical protocol to determine key properties of PLGA used in commercial long-acting drug products. Procedures to isolate PLGA from commercial products have been established and the key properties of PLGA, such as polymer molecular weight, lactide:glycolide (L:G) ratio, and nature of polymer end-cap, have been determined. Identification of the polymer end-cap was confirmed by using two PLGA polymers with acid and ester end-caps. Trelstar (R) and Risperdal Consta (R) were chosen as model products. The calculated L:G ratios of PLGA used in Trelstar (R) and Risperdal (R) are 52:48 and 78:22, respectively. PLGAs from both Trelstar (R) and Risperdal Consta (R) possess ester end-caps. Since the properties of specific PLGA in clinically used formulations are not readily available, this protocol will be useful in developing PLGA-based long acting drug products. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Garner, John; Skidmore, Sarah; Park, Haesun; Park, Kinam] Akina Inc, W Lafayette, IN 47906 USA.
[Choi, Stephanie; Wang, Yan] US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Silver Spring, MD 20993 USA.
RP Park, K (reprint author), Akina Inc, 3495 Kent Ave,Suite O-100, W Lafayette, IN 47906 USA.
EM pk@akinainc.com
OI Garner, John/0000-0002-8024-5061; Garner, John/0000-0002-6496-7654
FU Food and Drug Administration (FDA), Center for Drug Evaluation Research
(CDER) [U01FD05168]
FX Research reported in this publication was supported by Grant U01FD05168
from the Food and Drug Administration (FDA), Center for Drug Evaluation
Research (CDER). This article reflects the views of the authors and
should not be construed to represent FDA's views or policies. The
authors would like to thank the Purdue Interdepartmental Nuclear
Magnetic Resonance Facility (PINMRF) group.
NR 23
TC 0
Z9 0
U1 2
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5173
EI 1873-3476
J9 INT J PHARMACEUT
JI Int. J. Pharm.
PD NOV 10
PY 2015
VL 495
IS 1
BP 87
EP 92
DI 10.1016/j.ijpharm.2015.08.063
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CT7CE
UT WOS:000362970000011
PM 26319639
ER
EF