FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Iarikov, DE Alexander, J Nambiar, S AF Iarikov, Dmitri E. Alexander, John Nambiar, Sumathi TI Hypersensitivity Reactions Associated With Fidaxomicin Use SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE fidaxomicin; adverse reactions; hypersensitivity AB We report hypersensitivity reactions associated with fidaxomicin, an antibacterial drug approved for the treatment of Clostridium difficile-associated diarrhea. These reactions are viewed as significant because of severity and unexpected because fidaxomicin is minimally absorbed. The fidaxomicin labeling was revised to include information about the possibility of hypersensitivity reactions. C1 [Iarikov, Dmitri E.; Alexander, John; Nambiar, Sumathi] US FDA, Div Antiinfect Prod, Silver Spring, MD USA. RP Iarikov, DE (reprint author), 10903 New Hampshire Ave,Bldg 22,Room 6245, Silver Spring, MD 20993 USA. EM dmitri.iarikov@fda.hhs.gov NR 3 TC 2 Z9 2 U1 0 U2 3 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 2014 VL 58 IS 4 BP 537 EP 539 DI 10.1093/cid/cit719 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AA4WQ UT WOS:000331097800016 PM 24178248 ER PT J AU Jester, ELE Abraham, A Wang, YS El Said, KR Plakas, SM AF Jester, Edward L. E. Abraham, Ann Wang, Yuesong El Said, Kathleen R. Plakas, Steven M. TI Performance evaluation of commercial ELISA kits for screening of furazolidone and furaltadone residues in fish SO FOOD CHEMISTRY LA English DT Article DE ELISA; Furazolidone; Furaltadone ID CATFISH ICTALURUS-PUNCTATUS; TISSUE-BOUND METABOLITES; CHANNEL CATFISH; DEPLETION AB Regulatory monitoring for nitrofuran drug residues in aquaculture products has largely focused on LC-MS/MS. In addition, there is a need for facile and high-throughput screening methods for monitoring programs. We evaluated the performance of Ridascreen (R-Biopharm) ELISA kits for nitrofuran drug residues in fish muscle, with verification by LC-MS/MS. Kits were available for 3-amino-2-oxazolidinone (AOZ) and 3-amino-5-morpholino-methyl-2-oxazolidinone (AMOZ) side-chains of furazolidone and furaltadone, respectively. We found good repeatability in fortified and incurred muscle samples, with RSDs ranging from 1.8% to 7.6%. Recoveries of AOZ and AMOZ from muscle fortified at levels of 0.5-2 ng/g ranged from 98% to 114%. Excellent selectivity was demonstrated. The minimum detection limits (MDLs) for AOZ and AMOZ in muscle were 0.05 and 0.2 ng/g, respectively. ELISA data were highly correlated with those of LC-MS/MS. Results of this study support the use of these kits as screening assays for nitrofuran residues in fish muscle. Published by Elsevier Ltd. C1 [Jester, Edward L. E.; Abraham, Ann; Wang, Yuesong; El Said, Kathleen R.; 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 9 Z9 11 U1 4 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 FEB 15 PY 2014 VL 145 BP 593 EP 598 DI 10.1016/j.foodchem.2013.08.090 PG 6 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 261SP UT WOS:000327685200079 PM 24128519 ER PT J AU Ouyang, WM Torigoe, C Fang, H Xie, T Frucht, DM AF Ouyang, Weiming Torigoe, Chikako Fang, Hui Xie, Tao Frucht, David M. TI Anthrax Lethal Toxin Inhibits Translation of Hypoxia-inducible Factor 1 alpha and Causes Decreased Tolerance to Hypoxic Stress SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Bacillus; Bacterial Pathogenesis; Hypoxia; Hypoxia-inducible Factor; Infectious Diseases; MAP kinases (MAPKs); mTOR; Protein Stability; Toxins; Translation ID HIPPEL-LINDAU PROTEIN; SIGNALING PATHWAYS; INNATE IMMUNITY; BACILLUS-ANTHRACIS; SYSTEMIC ANTHRAX; KEY MEDIATOR; HIF-1-ALPHA; FACTOR-1-ALPHA; TARGETS; KINASE AB Background: Hypoxia is proposed as a mediator of anthrax lethal factor (LT)-induced pathology. Results: LT inhibits hypoxia-inducible factor 1 (HIF-1) translation and causes increased cellular toxicity in response to hypoxic stress. Conclusion: LT reduces HIF-1 translation, dysregulating host responses to hypoxia. Significance: Inhibition of HIF-1 translation is a novel mechanism underlying LT-induced pathology. Hypoxia is considered to be a contributor to the pathology associated with administration of anthrax lethal toxin (LT). However, we report here that serum lactate levels in LT-treated mice are reduced, a finding inconsistent with the anaerobic metabolism expected to occur during hypoxia. Reduced lactate levels are also observed in the culture supernatants of LT-treated cells. LT inhibits the accumulation of hypoxia-inducible factor (HIF)-1, a subunit of HIF-1, the master regulator directing cellular responses to hypoxia. The toxin has no effect on the transcription or protein turnover of HIF-1, but instead it acts to inhibit HIF-1 translation. LT treatment diminishes phosphorylation of eIF4B, eIF4E, and rpS6, critical components of the intracellular machinery required for HIF-1 translation. Moreover, blockade of MKK1/2-ERK1/2, but not p38 or JNK signaling, lowers HIF-1 protein levels in both normoxic and hypoxic conditions, consistent with a role for MKK1 and MKK2 as the major targets of LT responsible for the inhibition of HIF-1 translation. The physiological importance of the LT-induced translation blockade is demonstrated by the finding that LT treatment decreases the survival of hepatocyte cell lines grown in hypoxic conditions, an effect that is overcome by preinduction of HIF-1. Taken together, these data support a role for LT in dysregulating HIF-1 and thereby disrupting homeostatic responses to hypoxia, an environmental characteristic of certain tissues at baseline and/or during disseminated infection with Bacillus anthracis. C1 [Ouyang, Weiming; Torigoe, Chikako; Fang, Hui; Xie, Tao; Frucht, David M.] US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Frucht, DM (reprint author), US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. EM david.frucht@fda.hhs.gov FU Food and Drug Administration FX This work was supported by a Medical Countermeasures Grant from the Food and Drug Administration. NR 58 TC 1 Z9 1 U1 0 U2 6 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 FEB 14 PY 2014 VL 289 IS 7 BP 4180 EP 4190 DI 10.1074/jbc.M113.530006 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA9HG UT WOS:000331403800031 PM 24366872 ER PT J AU Orza, AI Mihu, C Soritau, O Diudea, M Florea, A Matei, H Balici, S Mudalige, T Kanarpardy, GK Biris, AS AF Orza, Anamaria I. Mihu, Carmen Soritau, Olga Diudea, Mircea Florea, Adrian Matei, Horea Balici, Stefana Mudalige, Thilak Kanarpardy, Ganesh K. Biris, Alexandru S. TI Multistructural biomimetic substrates for controlled cellular differentiation SO NANOTECHNOLOGY LA English DT Article DE nanomaterials; stem cell differentiation; gold-functionalized collagen-laminin substrate; extracellular matrix ID MESENCHYMAL STEM-CELLS; MULTIWALLED CARBON NANOTUBES; TYPE-1 DIABETES-MELLITUS; EXTRACELLULAR-MATRIX; GOLD NANOPARTICLES; HEPATOCELLULAR-CARCINOMA; NEURAL DIFFERENTIATION; REGENERATIVE MEDICINE; PARKINSONS-DISEASE; FOCAL ADHESIONS AB Multidimensional scaffolds are considered to be ideal candidates for regenerative medicine and tissue engineering based on their potential to provide an excellent microenvironment and direct the fate of the cultured cells. More recently, the use of stem cells in medicine has opened a new technological opportunity for controlled tissue formation. However, the mechanism through which the substrate directs the differentiation of stem cells is still rather unclear. Data concerning its specific surface chemistry, topology, and its signaling ability need to be further understood and analyzed. In our study, atomic force microscopy was used to study the stiffness, roughness, and topology of the collagen (Coll) and metallized collagen (MC) substrates, proposed as an excellent substrate for regenerative medicine. The importance of signaling molecules was studied by constructing a new hybrid signaling substrate that contains both collagen and laminin extracellular matrix (ECM) proteins. The cellular response-such as attachment capability, proliferation and cardiac and neuronal phenotype expression on the metallized and non-metallized hybrid substrates (collagen + laminin)-was studied using MTT viability assay and immunohistochemistry studies. Our findings indicate that such hybrid materials could play an important role in the regeneration of complex tissues. C1 [Orza, Anamaria I.; Diudea, Mircea] Univ Arkansas, Ctr Integrat Nanotechnol Sci, Little Rock, AR 72204 USA. [Orza, Anamaria I.; Kanarpardy, Ganesh K.; Biris, Alexandru S.] Inst Oncol, Cluj Napoca, Romania. [Mihu, Carmen] Univ Babes Bolyai, Fac Chem & Chem Engn, R-3400 Cluj Napoca, Romania. [Soritau, Olga; Florea, Adrian; Matei, Horea; Balici, Stefana] Iuliu Hatieganu Univ Med & Pharm, Dept Cell & Mol Biol, Cluj Napoca 400349, Romania. [Mudalige, Thilak] US FDA, Arkansas Reg Lab, Jefferson, AR 72079 USA. RP Orza, AI (reprint author), Univ Arkansas, Ctr Integrat Nanotechnol Sci, 2801 South Univ Ave, Little Rock, AR 72204 USA. EM anamaria.orza@emory.edu RI Diudea, Mircea/C-6838-2014 NR 81 TC 6 Z9 6 U1 2 U2 35 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0957-4484 EI 1361-6528 J9 NANOTECHNOLOGY JI Nanotechnology PD FEB 14 PY 2014 VL 25 IS 6 AR 065102 DI 10.1088/0957-4484/25/6/065102 PG 13 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Science & Technology - Other Topics; Materials Science; Physics GA 296OP UT WOS:000330194800002 PM 24434767 ER PT J AU Dong, JL Song, LN Yin, JJ He, WW Wu, YH Gu, N Zhang, Y AF Dong, Jinlai Song, Lina Yin, Jun-Jie He, Weiwei Wu, Yihang Gu, Ning Zhang, Yu TI Co3O4 Nanoparticles with Multi-Enzyme Activities and Their Application in Immunohistochemical Assay SO ACS APPLIED MATERIALS & INTERFACES LA English DT Article DE cobalt oxide nanoparticles; multi-enzyme mimetics; high redox potential; immunohistochemical assay ID IRON-OXIDE NANOPARTICLES; PEROXIDASE-LIKE ACTIVITY; LITHIUM-ION BATTERIES; TRANSITION-METALS; HYDROXYL RADICALS; SUPEROXIDE; OXIDATION; OXYGEN; VEGF; NANOSTRUCTURES AB Co3O4 nanoparticles (Co3O4 NPs), synthesized by the coprecipitation method, showed intrinsic catalase-like, peroxidase-like, and SOD-like activity. The catalytic activity of Co3O4 NPs was much higher than analogous Fe3O4 NPs. Co3O4's mechanisms of catalytic activity were analyzed in detail using the electron spin resonance (ESR) method, which confirmed that Co3O4 NPs don't follow the classical Fenton reactions with hydrogen peroxide the way Fe3O4 NPs do. The high redox potential of Co3+/Co2+ was supposed to be the leading cause of the differences in both activity and mechanism with Fe3O4. Based on the high, peroxidase-like activity, a new immunohistochemical assay was designed in which the avastin antibody was conjugated onto the surface of Co3O4 NPs. The conjugates obtained were used to detect vascular endothelial growth factor (VEGF) that was overexpressed in tumor tissue. When the experimental and control groups were stained, there were clear distinctions between them. This study showed that there are many opportunities to improve the enzyme-like activities of nanomaterials and also to improve their potential applications for biocatalysis and bioassays, especially in relatively harsh conditions. C1 [Dong, Jinlai; Song, Lina; Wu, Yihang; Gu, Ning; Zhang, Yu] Southeast Univ, State Key Lab Bioelect, Jiangsu Key Lab Biomat & Devices, Sch Biol Sci & Med Engn, Nanjing 210096, Jiangsu, Peoples R China. [Yin, Jun-Jie; He, Weiwei] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Gu, N (reprint author), Southeast Univ, State Key Lab Bioelect, Jiangsu Key Lab Biomat & Devices, Sch Biol Sci & Med Engn, Nanjing 210096, Jiangsu, Peoples R China. EM zhangyu@seu.edu.cn RI Yin, Jun Jie /E-5619-2014 FU National Basic Research Program of China [2011CB933503, 2013CB733800]; National Natural Science Foundation of China [31170959, 61127002]; Basic Research Program of Jiangsu Province (Natural Science Foundation) [BK2011036]; Research Fund for the Doctoral Program of Higher Education of China [20110092110029]; National Key Technology Research and Development Program of China [2012BAI23B02]; FDA Nanotechnology CORES Program; Office of Cosmetics and Colors, CFSAN/FDA FX We would like to thank Barbara Berman for editorial assistance. This research was supported by the National Basic Research Program of China (No. 2011CB933503, 2013CB733800), the National Natural Science Foundation of China (No. 31170959, 61127002), the Basic Research Program of Jiangsu Province (Natural Science Foundation, No. BK2011036), the Research Fund for the Doctoral Program of Higher Education of China (20110092110029), and the National Key Technology Research and Development Program of China (2012BAI23B02). It was also partially supported by a regulatory science grant under the FDA Nanotechnology CORES Program and by the Office of Cosmetics and Colors, CFSAN/FDA (W.H. and J.Y.). 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. NR 47 TC 36 Z9 37 U1 18 U2 108 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1944-8244 J9 ACS APPL MATER INTER JI ACS Appl. Mater. Interfaces PD FEB 12 PY 2014 VL 6 IS 3 BP 1959 EP 1970 DI 10.1021/am405009f PG 12 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Science & Technology - Other Topics; Materials Science GA AB0OY UT WOS:000331493200082 PM 24387092 ER PT J AU Khairuzzaman, A Ahmed, SU Higuera, A Bellantone, RA AF Khairuzzaman, A. Ahmed, S. U. Higuera, A. Bellantone, R. A. TI Effect of excipient porosity on the melting behavior of imbibed frozen liquids SO THERMOCHIMICA ACTA LA English DT Article DE Differential scanning calorimetry; Melting point depression; Gibbs-Thompson equation; Imbibed liquids ID DRUG-RELEASE KINETICS; THERMOPOROMETRY; WATER; PARAMETERS; TABLETS; EROSION; MATRIX AB The effect of excipient porosity on melting point depression of confined fluids was investigated. Two grades of the pharmaceutical excipient silicon dioxide, Syloid 244 FP and Syloid 74 Regular, were used as model porous excipients. The pore size distribution for each was characterized by nitrogen gas adsorption. The excipient pores were loaded with two liquids, water and cyclohexane, which were allowed to imbibe into the pores. The loaded excipients were then subjected to thermal analysis by cooling then heating, and the melting behavior of the imbibed frozen material was evaluated using differential scanning calorimetry (DSC). A mathematical model for the observed DSC thermograms was developed from the Gibbs-Thompson equation, which was used to relate the melting point depression of materials to the local curvature and the local surface energy per volume of imbibed material inside the pores. In all cases, two distinct melt behaviors were seen. One was a melt peak near the nominal melting temperature, corresponding to frozen fluids outside the pores. The other was a secondary satellite endotherm, which showed a melting point depression that occurred over a broad temperature range that was distinctly below the nominal melting temperature. This satellite endotherm was attributed to melting of the imbibed material in the pores, and the model equations were fit to the experimental DSC data. The local surface energies per volume of imbibed material were calculated for each case. These corresponded to apparent interfacial tensions between the imbibed material and the Syloid pore walls of 58-71 mJ/m(2) for water and 13 mJ/m(2) for cyclohexane. The data show that the excipient porosity can cause remarkable melting point depression, and the results of the modeling suggested that this analytical technique may represent a novel approach to assess the impact of surface area on small particles. (C) 2013 Elsevier B.V. All rights reserved. C1 [Khairuzzaman, A.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Ahmed, S. U.] Abon Pharmaceut LLC, Northvale, NJ 07647 USA. [Higuera, A.] OSI Pharmaceut, Farmingdale, NY 11735 USA. [Bellantone, R. A.] Long Isl Univ, Arnold & Marie Schwartz Coll Pharm & Hlth Sci, Div Pharmaceut Sci, Brooklyn, NY 11201 USA. RP Bellantone, RA (reprint author), Long Isl Univ, Arnold & Marie Schwartz Coll Pharm & Hlth Sci, Div Pharmaceut Sci, 75 Dekalb Ave, Brooklyn, NY 11201 USA. EM rbellant@liu.edu OI Bellantone, Robert/0000-0001-6750-2847 FU Barr Pharmaceuticals (Pomona, New York) FX This work is based in part on the Ph.D. Dissertation of Akm Khairuzzaman. The authors would like to express their gratitude to Barr Pharmaceuticals (Pomona, New York) for its support of this research. NR 21 TC 1 Z9 1 U1 3 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0040-6031 EI 1872-762X J9 THERMOCHIM ACTA JI Thermochim. Acta PD FEB 10 PY 2014 VL 577 BP 53 EP 58 DI 10.1016/j.tca.2013.12.013 PG 6 WC Thermodynamics; Chemistry, Analytical; Chemistry, Physical SC Thermodynamics; Chemistry GA AB3JU UT WOS:000331687900009 ER PT J AU Khalaj, M Abbasi, A Yamanishi, H Akiyama, K Wakitani, S Kikuchi, S Hirose, M Yuzuriha, M Magari, M Degheidy, HA Abe, K Ogura, A Hashimoto, H Kunieda, T AF Khalaj, Maryam Abbasi, Abdolrahim Yamanishi, Hiroshi Akiyama, Kouyou Wakitani, Shuso Kikuchi, Sotaro Hirose, Michiko Yuzuriha, Misako Magari, Masaki Degheidy, Heba A. Abe, Kuniya Ogura, Atsuo Hashimoto, Hiroshi Kunieda, Tetsuo TI A Missense Mutation in Rev7 Disrupts Formation of Pol zeta, Impairing Mouse Development and Repair of Genotoxic Agent-induced DNA Lesions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Cell Proliferation; DNA Polymerase; Embryo; Mouse Genetics; Mutant ID PRIMORDIAL GERM-CELLS; CROSS-LINK REPAIR; POLYMERASE-ZETA; FANCONI-ANEMIA; EMBRYONIC LETHALITY; CHROMOSOMAL INSTABILITY; GENOMIC INSTABILITY; CATALYTIC SUBUNIT; MAMMALIAN-CELLS; B-CELLS AB Background:Rev7 encodes a subunit of Pol for translesion DNA synthesis (TLS). Results: We found a Rev7 mutation in mice that causes developmental defects and increases susceptibility for genotoxicity. Conclusion:Rev7 is essential for mouse development through its function in cell proliferation. Significance: These findings demonstrate a unique function of Pol in development that is absent in other TLS polymerases. Repro22 is a mutant mouse produced via N-ethyl-N-nitrosourea-induced mutagenesis that shows sterility with germ cell depletion caused by defective proliferation of primordial germ cells, decreased body weight, and partial lethality during embryonic development. Using a positional cloning strategy, we identified a missense mutation in Rev7/Mad2l2 (Rev7(C70R)) and confirmed that the mutation is the cause of the defects in repro22 mice through transgenic rescue with normal Rev7. Rev7/Mad2l2 encodes a subunit of DNA polymerase (Pol), 1 of 10 translesion DNA synthesis polymerases known in mammals. The mutant REV7 did not interact with REV3, the catalytic subunit of Pol. Rev7(C70R/C70R) cells showed decreased proliferation, increased apoptosis, and arrest in S phase with extensive H2AX foci in nuclei that indicated accumulation of DNA damage after treatment with the genotoxic agent mitomycin C. The Rev7(C70R) mutation does not affect the mitotic spindle assembly checkpoint. These results demonstrated that Rev7 is essential in resolving the replication stalls caused by DNA damage during S phase. We concluded that Rev7 is required for primordial germ cell proliferation and embryonic viability and development through the translesion DNA synthesis activity of Pol preserving DNA integrity during cell proliferation, which is required in highly proliferating embryonic cells. C1 [Khalaj, Maryam; Abbasi, Abdolrahim; Yamanishi, Hiroshi; Wakitani, Shuso; Magari, Masaki] Okayama Univ, Grad Sch Nat Sci & Technol, Okayama 7008530, Japan. [Akiyama, Kouyou; Kunieda, Tetsuo] Okayama Univ, Grad Sch Environm & Life Sci, Okayama 7008530, Japan. [Khalaj, Maryam; Abbasi, Abdolrahim] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. [Kikuchi, Sotaro; Hashimoto, Hiroshi] Yokohama City Univ, Grad Sch Nanobiosci, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. [Hirose, Michiko; Yuzuriha, Misako; Abe, Kuniya; Ogura, Atsuo] RIKEN Bioresource Ctr, Tsukuba, Ibaraki 3050074, Japan. [Degheidy, Heba A.] US FDA, Div Biol, Silver Spring, MD 20993 USA. RP Abbasi, A (reprint author), NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. EM abbasiar@mail.nih.gov; tkunieda@cc.okayama-u.ac.jp RI Ogura, Atsuo/J-3916-2014 OI Ogura, Atsuo/0000-0003-0447-1988 FU Japan Society for the Promotion of Science FX This work was authored, in whole or in part, by National Institutes of Health staff. This work was supported in part by grants from the Japan Society for the Promotion of Science. NR 60 TC 10 Z9 10 U1 0 U2 5 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 FEB 7 PY 2014 VL 289 IS 6 BP 3811 EP 3824 DI 10.1074/jbc.M113.514752 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA8TU UT WOS:000331368700060 PM 24356953 ER PT J AU Mendicino, M Bailey, AM Wonnacott, K Puri, RK Bauer, SR AF Mendicino, Michael Bailey, Alexander M. Wonnacott, Keith Puri, Raj K. Bauer, Steven R. TI MSC-Based Product Characterization for Clinical Trials: An FDA Perspective SO CELL STEM CELL LA English DT Editorial Material ID MESENCHYMAL STROMAL CELLS; POTENCY AB Proposals submitted to the FDA for MSC-based products are undergoing a rapid expansion that is characterized by increased variability in donor and tissue sources, manufacturing processes, proposed functional mechanisms, and characterization methods. Here we discuss the diversity in MSC-based clinical trial product proposals and highlight potential challenges for clinical translation. C1 [Mendicino, Michael] OC, ORSI, OCS, Silver Spring, MD 20993 USA. [Mendicino, Michael; Wonnacott, Keith; Puri, Raj K.; Bauer, Steven R.] CBER, OCTGT, DCGT, Rockville, MD 20852 USA. [Bailey, Alexander M.] CBER, OCTGT, DCEPT, Rockville, MD 20852 USA. RP Mendicino, M (reprint author), OC, ORSI, OCS, 10903 New Hampshire Blvd, Silver Spring, MD 20993 USA. EM m.mendicino.phd@gmail.com; steven.bauer@fda.hhs.gov NR 10 TC 57 Z9 61 U1 0 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD FEB 6 PY 2014 VL 14 IS 2 BP 141 EP + DI 10.1016/j.stem.2014.01.013 PG 7 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA AA1DF UT WOS:000330835800006 PM 24506881 ER PT J AU Yih, WK Lieu, TA Kulldorff, M Martin, D McMahill-Walraven, CN Platt, R Selvam, N Selvan, M Lee, GM Nguyen, M AF Yih, W. Katherine Lieu, Tracy A. Kulldorff, Martin Martin, David McMahill-Walraven, Cheryl N. Platt, Richard Selvam, Nandini Selvan, Mano Lee, Grace M. Nguyen, Michael TI Intussusception Risk after Rotavirus Vaccination in US Infants SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID UNITED-STATES; LESS-THAN-5 YEARS; SAFETY; CHILDREN; PROGRAM; MEXICO; HOSPITALIZATIONS; SURVEILLANCE; IMMUNIZATION; PENTAVALENT AB BackgroundInternational postlicensure studies have identified an increased risk of intussusception after vaccination with the second-generation rotavirus vaccines RotaTeq (RV5, a pentavalent vaccine) and Rotarix (RV1, a monovalent vaccine). We studied this association among infants in the United States. MethodsThe study included data from infants 5.0 to 36.9 weeks of age who were enrolled in three U.S. health plans that participate in the Mini-Sentinel program sponsored by the Food and Drug Administration. Potential cases of intussusception and vaccine exposures from 2004 through mid-2011 were identified through procedural and diagnostic codes. Medical records were reviewed to confirm the occurrence of intussusception and the status with respect to rotavirus vaccination. The primary analysis used a self-controlled risk-interval design that included only vaccinated children. The secondary analysis used a cohort design that included exposed and unexposed person-time. ResultsThe analyses included 507,874 first doses and 1,277,556 total doses of RV5 and 53,638 first doses and 103,098 total doses of RV1. The statistical power for the analysis of RV1 was lower than that for the analysis of RV5. The number of excess cases of intussusception per 100,000 recipients of the first dose of RV5 was significantly elevated, both in the primary analysis (attributable risk, 1.1 [95% confidence interval, 0.3 to 2.7] for the 7-day risk window and 1.5 [95% CI, 0.2 to 3.2] for the 21-day risk window) and in the secondary analysis (attributable risk, 1.2 [95% CI, 0.2 to 3.2] for the 21-day risk window). No significant increase in risk was seen after dose 2 or 3. The results with respect to the primary analysis of RV1 were not significant, but the secondary analysis showed a significant risk after dose 2. ConclusionsRV5 was associated with approximately 1.5 (95% CI, 0.2 to 3.2) excess cases of intussusception per 100,000 recipients of the first dose. The secondary analysis of RV1 suggested a potential risk, although the study of RV1 was underpowered. These risks must be considered in light of the demonstrated benefits of rotavirus vaccination. (Funded by the Food and Drug Administration.) Rotavirus vaccination has been associated with a decline in rotavirus-associated illness, but intussusception remains a concern. In this study, the pentavalent rotavirus vaccine was associated with a slight increase in intussusception, as compared with the monovalent vaccine. In 1999, a tetravalent rhesus-human reassortant rotavirus vaccine (RotaShield, Wyeth Lederle) was voluntarily withdrawn from the U.S. market within a year after licensure owing to an association with intussusception. The excess risk of intussusception was estimated at approximately 1 to 2 cases per 10,000 recipients of the vaccine.(1) In 2006 and 2008, respectively, a pentavalent bovine-human reassortant rotavirus vaccine (RV5; RotaTeq, Merck) and a monovalent human rotavirus vaccine (RV1; Rotarix, GlaxoSmithKline) were licensed after evaluation in clinical trials involving more than 60,000 infants, which provided enough statistical power to allow detection of an intussusception risk of a magnitude similar to ... C1 [Yih, W. Katherine; Lieu, Tracy A.; Kulldorff, Martin; Platt, Richard; Lee, Grace M.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02215 USA. [Yih, W. Katherine; Lieu, Tracy A.; Kulldorff, Martin; Platt, Richard; Lee, Grace M.] Harvard Pilgrim Hlth Care Inst, Boston, MA 02215 USA. [Lee, Grace M.] Boston Childrens Hosp, Div Infect Dis, Boston, MA USA. [Lee, Grace M.] Boston Childrens Hosp, Dept Lab Med, Boston, MA USA. [Lieu, Tracy A.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Martin, David; Nguyen, Michael] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [McMahill-Walraven, Cheryl N.] Aetna, Blue Bell, PA USA. [Selvam, Nandini] HealthCore, Govt & Acad Res, Alexandria, VA USA. [Selvan, Mano] Humana, Comprehens Hlth Insights, Louisville, KY USA. RP Yih, WK (reprint author), Harvard Univ, Sch Med, Dept Populat Med, 133 Brookline Ave,6th Fl, Boston, MA 02215 USA. EM katherine_yih@harvardpilgrim.org OI Kulldorff, Martin/0000-0002-5284-2993 FU Food and Drug Administration FX Funded by the Food and Drug Administration. NR 33 TC 77 Z9 78 U1 2 U2 15 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 6 PY 2014 VL 370 IS 6 BP 503 EP 512 DI 10.1056/NEJMoa1303164 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AA4NT UT WOS:000331073500006 PM 24422676 ER PT J AU Mansfield, E Tyner, KM Poling, CM Blacklock, JL AF Mansfield, Elisabeth Tyner, Katherine M. Poling, Christopher M. Blacklock, Jenifer L. TI Determination of Nanoparticle Surface Coatings and Nanoparticle Purity Using Microscale Thermogravimetric Analysis SO ANALYTICAL CHEMISTRY LA English DT Article ID QUARTZ-CRYSTAL MICROBALANCE; GOLD NANOPARTICLES; TEMPERATURE; CHEMISTRY; OXIDATION; DENSITY AB The use of nanoparticles in some applications (i.e., nanomedical, nanofiltration, or nanoelectronic) requires small samples with well-known purities and composition. In addition, when nanoparticles are introduced into complex environments (e.g., biological fluids), the particles may become coated with matter, such as proteins or lipid layers. Many of today's analytical techniques are not able to address small-scale samples of nanoparticles to determine purity and the presence of surface coatings. Through the use of an elevated-temperature quartz crystal microbalance (QCM) method we call microscale thermogravimetric analysis, or mu-TGA, the nanoparticle purity, as well as the presence of any surface coatings of nanomaterials, can be measured. Microscale thermogravimetric analysis is used to determine the presence and amount of surface-bound ligand coverage on gold nanoparticles and confirm the presence of a poly(ethylene glycol) coating on SiO2 nanoparticles. Results are compared to traditional analytical techniques to demonstrate reproducibility and validity of mu-TGA for determining the presence of nanoparticle surface coatings. Carbon nanotube samples are also analyzed and compared to conventional TGA. The results demonstrate mu-TGA is a valid method for quantitative determination of the coatings on nanoparticles, and in some cases, can provide purity and compositional data of the nanoparticles themselves. C1 [Mansfield, Elisabeth; Poling, Christopher M.; Blacklock, Jenifer L.] NIST, Appl Chem & Mat Div, Boulder, CO 80305 USA. [Tyner, Katherine M.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Mansfield, E (reprint author), NIST, Appl Chem & Mat Div, Boulder, CO 80305 USA. EM elisabeth.mansfield@nist.gov NR 28 TC 10 Z9 10 U1 6 U2 42 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 EI 1520-6882 J9 ANAL CHEM JI Anal. Chem. PD FEB 4 PY 2014 VL 86 IS 3 BP 1478 EP 1484 DI 10.1021/ac402888v PG 7 WC Chemistry, Analytical SC Chemistry GA AA3TI UT WOS:000331014800026 PM 24400715 ER PT J AU Aryal, B Jeong, J Rao, VA AF Aryal, Baikuntha Jeong, Jinsook Rao, V. Ashutosh TI Doxorubicin-induced carbonylation and degradation of cardiac myosin binding protein C promote cardiotoxicity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; ROS; cardioprotection ID OXIDATIVE STRESS; HYPERTROPHIC CARDIOMYOPATHY; HL-1 CARDIOMYOCYTES; CATALYZED OXIDATION; MYBP-C; MUSCLE; ACTIN; THERAPY; MICE; IDENTIFICATION AB Dose-dependent oxidative stress by the anthracycline doxorubicin (Dox) and other chemotherapeutic agents causes irreversible cardiac damage, restricting their clinical effectiveness. We hypothesized that the resultant protein oxidation could be monitored and correlated with physiological functional impairment. We focused on protein carbonylation as an indicator of severe oxidative damage because it is irreversible and results in proteasomal degradation. We identified and investigated a specific high-molecular weight cardiac protein that showed a significant increase in carbonylation under Dox-induced cardiotoxic conditions in a spontaneously hypertensive rat model. We confirmed carbonylation and degradation of this protein under oxidative stress and prevention of such effect in the presence of the iron chelator dexrazoxane. Using MS, the Dox-induced carbonylated protein was identified as the 140-kDa cardiac myosin binding protein C (MyBPC). We confirmed the carbonylation and degradation of MyBPC using HL-1 cardiomyocytes and a purified recombinant untagged cardiac MyBPC under metal-catalyzed oxidative stress conditions. The carbonylation and degradation of MyBPC were time-and drug concentration-dependent. We demonstrated that carbonylated MyBPC undergoes proteasome-mediated degradation under Dox-induced oxidative stress. Cosedimentation, immunoprecipitation, and actin binding assays were used to study the functional consequences of carbonylated MyBPC. Carbonylation of MyBPC showed significant functional impairment associated with its actin binding properties. The dissociation constant of carbonylated recombinant MyBPC for actin was 7.35 +/- 1.9 mu M compared with 2.7 +/- 0.6 mu M for native MyBPC. Overall, our findings indicate that MyBPC carbonylation serves as a critical determinant of cardiotoxicity and could serve as a mechanistic indicator for Dox-induced cardiotoxicity. C1 [Aryal, Baikuntha; Jeong, Jinsook; Rao, V. Ashutosh] US FDA, Chem Lab, Div Therapeut Prot, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Rao, VA (reprint author), US FDA, Chem Lab, Div Therapeut Prot, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. EM ashutosh.rao@fda.hhs.gov FU Center for Drug Evaluation and Research Critical Path; Medical Countermeasures Initiative (MCMi) FX We acknowledge helpful discussions with Drs. Rodney L. Levine (National Institutes of Health), Melanie Simpson (National Cancer Institute), and Eugene H. Herman [Food and Drug Administration (FDA)]. We thank Dr. Melkamu G. Kebtie (FDA) and Dr. Shen Luo (FDA) for their help with MS. We acknowledge Prof. William C. Claycomb for kindly providing HL-1 cells. This research was supported by the Center for Drug Evaluation and Research Critical Path and Medical Countermeasures Initiative (MCMi) funding. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the United States 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 United States Government. NR 41 TC 15 Z9 15 U1 1 U2 16 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 FEB 4 PY 2014 VL 111 IS 5 BP 2011 EP 2016 DI 10.1073/pnas.1321783111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 302FL UT WOS:000330587600080 PM 24449919 ER PT J AU Qiu, YH Li, X Duan, JZ AF Qiu, Yihong Li, Xia Duan, John Z. TI Influence of Drug Property and Product Design on In Vitro-In Vivo Correlation of Complex Modified-Release Dosage Forms SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE modified release; bimodal release; dissolution; kinetics; absorption; disposition; pharmacokinetics; IVIVC; simulation; superposition ID PHARMACOKINETICS; BIOAVAILABILITY; ACETAMINOPHEN; FORMULATIONS; TRAMADOL AB The present study examines how drug's inherent properties and product design influence the evaluation and applications of in vitro-in vivo correlation (IVIVC) for modified-release (MR) dosage forms consisting of extended-release (ER) and immediate-release (IR) components with bimodal drug release. Three analgesic drugs were used as model compounds, and simulations of in vivo pharmacokinetic profiles were conducted using different release rates of the ER component and various IR percentages. Plasma concentration-time profiles exhibiting a wide range of t(max) and maximum observed plasma concentration (C-max) were obtained from superposition of the simulated IR and ER profiles based on a linear IVIVC. It was found that depending on the drug and dosage form design, direct use of the superposed IR and ER data for IVIVC modeling and prediction may (1) be acceptable within errors, (2) become unreliable and less meaningful because of the confounding effect from the non-negligible IR contribution to C-max, or (3) be meaningless because of the insensitivity of C-max to release rate change of the ER component. Therefore, understanding the drug, design and drug release characteristics of the product is essential for assessing the validity, accuracy, and reliability of IVIVC of complex MR products obtained via directly modeling of in vivo data. (C) 2013 Wiley Periodicals, Inc. C1 [Qiu, Yihong] AbbVie Inc, Oral Drug Prod Mfg Sci & Technol, N Chicago, IL 60064 USA. [Li, Xia; Duan, John Z.] US FDA, Off New Drug Qual Assessment, Silver Spring, MD USA. RP Qiu, YH (reprint author), AbbVie Inc, Oral Drug Prod Mfg Sci & Technol, N Chicago, IL 60064 USA. EM qiu.yihong@abbvie.com NR 26 TC 2 Z9 2 U1 0 U2 0 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 2014 VL 103 IS 2 BP 507 EP 516 DI 10.1002/jps.23804 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA AO4LW UT WOS:000341311100019 PM 24338862 ER PT J AU Cantor, SL Gupta, A Khan, MA AF Cantor, Stuart L. Gupta, Abhay Khan, Mansoor A. TI Analytical Methods for the Evaluation of Melamine Contamination SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE melamine; gelatin; near-infrared spectroscopy (NIRS); chemometrics; partial least squares; PLS; FTIR; infrared spectroscopy; Raman spectroscopy; X-ray diffractometry ID RATS AB There is an urgent need for the analysis of melamine in the global pharmaceutical supply chain to detect economically motivated adulteration or unintentional contamination using a simple, nondestructive analytical technique that confirms the extent of adulteration in a shorter time period. In this work, different analytical techniques (thermal analysis, X-ray diffraction, Fourier transform infrared (FT-IR), FT-Raman, and near-infrared (NIR) spectroscopy) were evaluated for their ability to detect a range of melamine levels in gelatin. While FT-IR and FT-Raman provided qualitative assessment of melamine contamination or adulteration, powder X-ray diffraction and NIR were able to detect and quantify the presence of melamine at levels as low as 1.0% w/w. Multivariate analysis of the NIR data yielded the most accurate model when three principal components were used. Data were pretreated using standard normal variate transformation to remove multiplicative interferences of scatter and particle size. The model had a root-mean-square error of calibration of 2.4 (R-2 = 0.99) and root-mean square error of prediction of 2.5 (R-2 = 0.96). The value of the paired t test for actual and predicted samples (1%-50% w/w) was 0.448 (p < 0.05), further indicating the robustness of the model. Published 2013. C1 [Cantor, Stuart L.; Gupta, Abhay; Khan, Mansoor A.] US FDA, Off Pharmaceut Sci, Div Prod Qual Res, Silver Spring, MD 20993 USA. RP Khan, MA (reprint author), US FDA, Off Pharmaceut Sci, Div Prod Qual Res, Silver Spring, MD 20993 USA. EM Mansoor.khan@fda.hhs.gov OI cantor, stuart/0000-0001-6506-1419 FU U.S. Department of Energy; CDER FX This project was also supported in part by an appointment to the ORISE Research Participation Program at CDER administered by the Oak Ridge Institute for Science and Education through an agreement between the U.S. Department of Energy and CDER. NR 12 TC 0 Z9 0 U1 2 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 FEB PY 2014 VL 103 IS 2 BP 539 EP 544 DI 10.1002/jps.23812 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA AO4LW UT WOS:000341311100022 PM 24327168 ER PT J AU Babu, US Balan, KV Garthoff, LH Calvo, MS AF Babu, Uma S. Balan, Kannan V. Garthoff, Larry H. Calvo, Mona S. TI Vitamin D-2 from UVB light exposed mushrooms modulates immune response to LPS in rats SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Article DE Inflammation; Lipopolysaccharide; Mushrooms; NK activity; Vitamin D2 ID SERUM 25-HYDROXYVITAMIN D; WHITE BUTTON MUSHROOMS; AGARICUS-BISPORUS; DIETARY SUPPLEMENTATION; EDIBLE MUSHROOMS; ULTRAVIOLET-IRRADIATION; UNITED-STATES; D DEFICIENCY; MICE; CHOLECALCIFEROL AB Scope: Poor vitamin D (vitD) status is linked to increased risk of infectious diseases, thus there is need for vitD-rich foods. UVB-exposed mushrooms synthesize vitD(2) but knowledge of bioavailability and function in immune response is lacking. Methods and results: One hundred rats were fed one of five diets-control, 20 IU vitD(3)/day; no vitD(3)/day; 5% unexposed mushroom, 2.4 IU vitD(2)/day; 2.5% UVB mushroom, 300 IU vitD(2)/day; and 5% UVB mushroom, 600 IU vitD(2)/day-for 10 wk and challenged with either saline or the endotoxin LPS. Blood and tissues were collected at 3 h postchallenge. Plasma 25-hydroxyvitamin D (25OHD) levels from UVB-exposed mushroom fed rats were significantly elevated and associated with higher natural killer cell activity and reduced plasma inflammatory response to LPS compared to control diet fed rats. Microarray evaluation of rat spleens for changes in inflammatory gene expression showed significant upregulation of proinflammatory genes after LPS compared to saline controls in all groups. However, compared to control rats, upregulation of the proinflammatory genes was markedly reduced in the groups fed vitD(2)-enriched mushrooms. Conclusion: Rats fed UVB-exposed mushrooms had significantly higher plasma total 25OHD levels that were associated with increased innate immune response and anti-inflammatory effects. C1 [Babu, Uma S.; Balan, Kannan V.; Garthoff, Larry H.; Calvo, Mona S.] US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Calvo, MS (reprint author), US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM mona.calvo@fda.hhs.gov FU Mushroom Council; US Food and Drug Administration Center for Food Safety and Applied Nutrition; FDA Commissioner's Fellowship Program; Oak Ridge Institute for Science and Education (ORISE) FX The authors thank the Mushroom Council and US Food and Drug Administration Center for Food Safety and Applied Nutrition for support. Kannan V. Balan was funded by the FDA Commissioner's Fellowship Program and Oak Ridge Institute for Science and Education (ORISE). NR 62 TC 4 Z9 4 U1 1 U2 9 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 2014 VL 58 IS 2 BP 318 EP 328 DI 10.1002/mnfr.201300286 PG 11 WC Food Science & Technology SC Food Science & Technology GA AJ4GA UT WOS:000337629700011 PM 24038984 ER PT J AU Zhang, J Knapton, A Lipshultz, SE Cochran, TR Hiraragi, H Herman, EH AF Zhang, Jun Knapton, Alan Lipshultz, Steven E. Cochran, Thomas R. Hiraragi, Hajime Herman, Eugene H. TI Sex-related Differences in Mast Cell Activity and Doxorubicin Toxicity: A Study in Spontaneously Hypertensive Rats SO TOXICOLOGIC PATHOLOGY LA English DT Article DE doxorubicin; cardiomyopathy; nephropathy; spontaneously hypertensive rats; ovariectomy; cardiac mast cells; renal mast cells ID ADRIAMYCIN-INDUCED CARDIOMYOPATHY; CONGESTIVE-HEART-FAILURE; OXIDATIVE STRESS; OVARIECTOMIZED RATS; INDUCED NEPHROPATHY; FEMALE RATS; RALOXIFENE TREATMENT; ANTIOXIDANT ENZYMES; DENDRITIC CELLS; FREE-RADICALS AB Clinically, girls appear to be more sensitive than boys to the cardiotoxic effects of doxorubicin, whereas the opposite may be true for adults. To identify and characterize potential sex-related differences, adult male and female spontaneously hypertensive rats (SHR; some ovariectomized [OVX]) received 1 mg/kg of doxorubicin or saline iv weekly for 9, 10, or 12 weeks. Weight gain was slower in treated males. Serum concentrations of cholesterol and triglycerides increased and those of albumin decreased in both sexes, but changes were more pronounced in treated males. Treated males had significantly more severe cardiomyopathy scores and higher serum levels of cTnT than females. The increased cardiotoxicity was accompanied by higher numbers of cardiac mast cells (MCs) and percentage of cardiac MCs undergoing degranulation. Doxorubicin-treated OVX animals had significantly increased numbers of cardiac MCs, more severe myocardial lesions, and elevated serum concentrations of cTnT compared to doxorubicin-treated normal female SHR. The severity of cardiac lesions in the OVX female was similar to that observed in doxorubicin-treated males. This study demonstrated the presence of sex-related differences in the cardiotoxic effects elicited by doxorubicin and identified variations in the level of cardiac MC activity as a factor which could possibly contribute to the male-female dissimilarity. C1 [Zhang, Jun; Knapton, Alan; Herman, Eugene H.] US FDA, Div Drug Safety Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Lipshultz, Steven E.; Cochran, Thomas R.] Univ Miami, Leonard M Miller Sch Med, Miami, FL USA. [Hiraragi, Hajime] Amgen Inc, Seattle, WA USA. RP Herman, EH (reprint author), US FDA, Div Drug Safety Res HFD 910, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM eugene.herman@fda.hhs.gov NR 45 TC 10 Z9 10 U1 0 U2 1 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 2014 VL 42 IS 2 BP 361 EP 375 DI 10.1177/0192623313482778 PG 15 WC Pathology; Toxicology SC Pathology; Toxicology GA AJ4ES UT WOS:000337625300008 PM 23531790 ER PT J AU Zhang, LS Zhang, J Shea, K Xu, L Tobin, G Knapton, A Sharron, S Rouse, R AF Zhang, Leshuai Zhang, Jun Shea, Katherine Xu, Lin Tobin, Grainne Knapton, Alan Sharron, Stewart Rouse, Rodney TI Autophagy in Pancreatic Acinar Cells in Caerulein-treated Mice: Immunolocalization of Related Proteins and Their Potential as Markers of Pancreatitis SO TOXICOLOGIC PATHOLOGY LA English DT Article DE apoptosis; autophagosome; lysosome; necrosis; trypsinogen activation ID DRUG-INDUCED PANCREATITIS; NITRIC-OXIDE SYNTHASE; CATHEPSIN-B; TRYPSINOGEN ACTIVATION; LYSOSOMAL CATHEPSINS; EXPERIMENTAL-MODELS; MEMBRANE-PROTEIN; ACID-PHOSPHATASE; APOPTOTIC DEATH; CANCER-CELLS AB Drug-induced pancreatitis (DIP) is an underdiagnosed condition that lacks sensitive and specific biomarkers. To better understand the mechanisms of DIP and to identify potential tissue biomarkers, we studied experimental pancreatitis induced in male C57BL/6 mice by intraperitoneal injection of caerulein (10 or 50 mu g/kg) at 1-hr intervals for a total of 7 injections. Pancreata from caerulein-treated mice exhibited consistent acinar cell autophagy and apoptosis with infrequent necrosis. Kinetic assays for serum amylase and lipase also showed a dose-dependent increase. Terminal deoxynucleotidyl transferase-mediated biotin-dNTP nick labeling (TUNEL) detected dose-dependent acinar cell apoptosis. By light microscopy, autophagy was characterized by the formation of autophagosomes and autolysosomes (ALs) within the cytoplasm of acinar cells. Immunohistochemical studies with specific antibodies for proteins related to autophagy and pancreatic stress were conducted to evaluate these proteins as potential biomarkers of pancreatitis. Western blots were used to confirm immunohistochemical results using pancreatic lysates from control and treated animals. Autophagy was identified as a contributing process in caerulein-induced pancreatitis and proteins previously associated with autophagy were upregulated following caerulein treatment. Autophagosomes and ALs were found to be a common pathway, in which cathepsins, lysosome-associated membrane protein 2, vacuole membrane protein 1, microtubule-associated protein 1 light chain 3 (LC3), autophagy-related protein 9, Beclin1, and pancreatitis-associated proteins were simultaneously involved in response to caerulein stimulus. Regenerating islet-derived 3 gamma (Reg3 gamma), a pancreatic acute response protein, was dose-dependently induced in caerulein-treated mice and colocalized with the autophagosomal marker, LC3. This finding supports Reg3 gamma as a candidate biomarker for pancreatic injury. C1 [Zhang, Leshuai; Zhang, Jun; Shea, Katherine; Xu, Lin; Tobin, Grainne; Knapton, Alan; Sharron, Stewart; Rouse, Rodney] US FDA, Div Drug Safety Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Rouse, R (reprint author), US FDA, Div Drug Safety Res, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM rodney.rouse@fda.hhs.gov RI Zhang, Leshuai/C-8077-2012 NR 91 TC 5 Z9 8 U1 0 U2 6 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 2014 VL 42 IS 2 BP 435 EP 457 DI 10.1177/0192623313486967 PG 23 WC Pathology; Toxicology SC Pathology; Toxicology GA AJ4ES UT WOS:000337625300014 PM 23640381 ER PT J AU Lazorick, S Crawford, Y Gilbird, A Fang, XM Burr, V Moore, V Hardison, GT AF Lazorick, Suzanne Crawford, Yancey Gilbird, Anthony Fang, Xiangming Burr, Veronica Moore, Valeria Hardison, George T., Jr. TI Long-Term Obesity Prevention and the Motivating Adolescents with Technology to CHOOSE Health (TM) Program SO CHILDHOOD OBESITY LA English DT Article ID CHILDHOOD OBESITY; PHYSICAL-ACTIVITY; PLANET-HEALTH; EDUCATION; POLICY; CATCH AB Background: The Motivating Adolescents with Technology to CHOOSE Health (TM) (MATCH) intervention integrates lifestyle behavior change curriculum within academic subjects taught in seventh grade. This study assesses obesity prevention in participants into high school. Methods: The study compares four-to five-year longitudinal data from a single-site cohort (N = 106, 54% retained from 195 participants at baseline; 82% of those still at the school) pre- and postintervention in a rural middle school with high obesity rates with data from the 2006 Child Survey and 2010 Child and Young Adult Surveys from the National Longitudinal Survey of Youth 1979 (N= 600), which serves as a nationally representative comparison group. Outcome measures include pre- and postchanges in weight category, BMI, BMI z-score, BMI percentile for age and gender, and rates of change per month in BMI measures. Results: At follow-up, change in percent overweight was significantly different between groups, with the MATCH group decreasing (20-12%) and the comparison group increasing (17-19%). Overall, the MATCH group had significantly higher decrease rates in BMI z-scores (p = 0.002) and BMI percentile (p = 0.01) than the comparison group. Of all adolescents at healthy weight at baseline, 2% from MATCH became overweight after five years, whereas 13% of the comparison group increased to overweight or obese (p = 0.02) after four years. Conclusions: Despite a small sample size and a high-risk setting, at long-term follow-up, a greater proportion of MATCH participants than in the comparison group decreased from overweight to healthy weight or remained at healthy weight. The MATCH results suggest that some proportion of high-risk adolescents can have their growth trajectory follow a healthier path than expected. C1 [Lazorick, Suzanne; Crawford, Yancey; Hardison, George T., Jr.] E Carolina Univ, Brody Sch Med, Dept Pediat, Greenville, NC 27834 USA. [Lazorick, Suzanne] E Carolina Univ, Brody Sch Med, Dept Publ Hlth, Greenville, NC 27834 USA. [Gilbird, Anthony] E Carolina Univ, Brody Sch Med, Off Human Res Integr, Greenville, NC 27834 USA. [Fang, Xiangming] E Carolina Univ, Coll Allied Hlth Sci, Dept Biostat, Greenville, NC 27834 USA. [Burr, Veronica] Veritas Collaborat, Durham, NC USA. [Moore, Valeria] US FDA, Off Regulatory Affairs, St Louis, MO USA. RP Lazorick, S (reprint author), E Carolina Univ, Brody Sch Med, 600 Moye Blvd,174 Life Sci Bldg, Greenville, NC 27834 USA. EM lazoricks@ecu.edu FU Blue Cross and Blue Shield of North Carolina Foundation; Robert Wood Johnson Foundation; MATCH; Martin County school FX This work was supported by funding from the Blue Cross and Blue Shield of North Carolina Foundation and, in part, by the Robert Wood Johnson Foundation Physician Faculty Scholar Award Program. An abstract of the MATCH results included in this article was presented as a poster at The Obesity Society 30th Annual Scientific Meeting, San Antonio, Texas, September 20-24, 2012. The authors acknowledge the several Martin County businesses that contributed a combined total of $6,500 of funding and supplies for MATCH, as well as backpacks that served as an incentive for participation in the follow-p measures. The authors also thank the Martin County school system personnel who supported this work, particularly administrative leadership during 2006-2008, including Superintendent Dr. Thomas Daly. Finally, the authors recognize Principal Clay Wagner, who supported MATCH at the middle school in 2006-2008, and then greatly facilitated the follow-up study as the high school principal in 2011-2012. NR 34 TC 7 Z9 7 U1 2 U2 11 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2153-2168 EI 2153-2176 J9 CHILD OBES JI Child Obes. PD FEB PY 2014 VL 10 IS 1 BP 25 EP 33 DI 10.1089/chi.2013.0049 PG 9 WC Pediatrics SC Pediatrics GA AI5GC UT WOS:000336892400005 PM 24325403 ER PT J AU Woo, EJ Winiecki, SK Ou, AC AF Woo, Emily Jane Winiecki, Scott K. Ou, Alan C. TI Motor palsies of cranial nerves (excluding VII) after vaccination Reports to the US Vaccine Adverse Event Reporting System SO HUMAN VACCINES & IMMUNOTHERAPEUTICS LA English DT Article DE vaccine; cranial nerve palsy; ptosis; disconjugate gaze; adverse event; postmarketing safety surveillance ID ATTENUATED INFLUENZA VACCINE; BELLS-PALSY; POSTMARKETING EVALUATION; UNITED-STATES; SAFETY; H1N1; VAERS; AGE AB We reviewed cranial nerve palsies, other than VII, that have been reported to the US Vaccine Adverse Event Reporting System (VAERS). We examined patterns for differences in vaccine types, seriousness, age, and clinical characteristics. We identified 68 reports of cranial nerve palsies, most commonly involving the oculomotor (III), trochlear (IV), and abducens (VI) nerves. Isolated cranial nerve palsies, as well as palsies occurring as part of a broader clinical entity, were reported. Forty reports (59%) were classified as serious, suggesting that a cranial nerve palsy may sometimes be the harbinger of a broader and more ominous clinical entity, such as a stroke or encephalomyelitis. There was no conspicuous clustering of live vs. inactivated vaccines. The patient age range spanned the spectrum from infants to the elderly. Independent data may help to clarify whether, when, and to what extent the rates of cranial nerve palsies following particular vaccines may exceed background levels. C1 [Woo, Emily Jane; Winiecki, Scott K.] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Ou, Alan C.] NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA. RP Woo, EJ (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM jane.woo@fda.hhs.gov OI Winiecki, Scott/0000-0003-4912-4621 NR 23 TC 2 Z9 2 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2164-5515 EI 2164-554X J9 HUM VACC IMMUNOTHER JI Human Vaccines Immunother. PD FEB PY 2014 VL 10 IS 2 BP 301 EP 305 DI 10.4161/hv.27032 PG 5 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA AI1YV UT WOS:000336652500014 PM 24231288 ER PT J AU Hess, CN McCoy, LA Duggirala, HJ Tavris, DR O'Callaghan, K Douglas, PS Peterson, ED Wang, TY AF Hess, Connie N. McCoy, Lisa A. Duggirala, Hesha J. Tavris, Dale R. O'Callaghan, Kathryn Douglas, Pamela S. Peterson, Eric D. Wang, Tracy Y. TI Sex-Based Differences in Outcomes After Percutaneous Coronary Intervention for Acute Myocardial Infarction: A Report From TRANSLATE-ACS SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE acute myocardial infarction; major adverse cardiac events; percutaneous coronary intervention; sex-based outcomes ID ACADEMIC RESEARCH CONSORTIUM; AMERICAN-HEART-ASSOCIATION; RAPID RISK STRATIFICATION; SUPPRESS ADVERSE OUTCOMES; GENDER-DIFFERENCES; EARLY IMPLEMENTATION; PRIMARY ANGIOPLASTY; CLINICAL-TRIALS; ARTERY-DISEASE; REGISTRY AB Background-Data regarding sex-based outcomes after percutaneous coronary intervention (PCI) for myocardial infarction are mixed. We sought to examine whether sex differences in outcomes exist in contemporary practice. Methods and Results-We examined acute myocardial infarction patients undergoing PCI between April 2010 and October 2012 at 210 US hospitals participating in the Treatment with Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) observational study. Outcomes included 1-year risk of major adverse cardiac events and bleeding according to Global Utilization of Strategies To Open Occluded Arteries (GUSTO) and Bleeding Academic Research Consortium (BARC) definitions. Among 6218 patients, 27.5% (n=1712) were female. Compared with men, women were older, had more comorbidities, and had lower functional status. Use of multivessel PCI and drug-eluting stents was similar between sexes, while women received less prasugrel. Unadjusted cumulative incidence of 1-year major adverse cardiac events was higher for women than for men (15.7% versus 13.6%, P=0.02), but female sex was no longer associated with higher incidence of major adverse cardiac events after multivariable adjustment (hazard ratio 0.98, 95% CI 0.83 to 1.15). Female sex was associated with higher risks of post-PCI GUSTO bleeding (9.1% versus 5.7%, P<0.0001) and postdischarge BARC bleeding (39.6% versus 27.9%, P<0.0001). Differences persisted after adjustment (GUSTO: hazard ratio 1.32, 95% CI 1.06 to 1.64; BARC: incidence rate ratio 1.42, 95% CI 1.27 to 1.56). Conclusions-Female and male myocardial infarction patients undergoing PCI differ regarding demographic, clinical, and treatment profiles. These differences appear to explain the higher observed major adverse cardiac event rate but not higher adjusted bleeding risk for women versus men. C1 [Hess, Connie N.; McCoy, Lisa A.; Douglas, Pamela S.; Peterson, Eric D.; Wang, Tracy Y.] Duke Clin Res Inst, Durham, NC USA. [Duggirala, Hesha J.; Tavris, Dale R.; O'Callaghan, Kathryn] US FDA, Silver Spring, MD USA. RP Hess, CN (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, 2400 Pratt St,Room 0311,Terrace Level, Durham, NC 27705 USA. EM connie.hess@duke.edu FU Food and Drug Administration Office of Women's Health; Daiichi Sankyo, Ltd; Eli Lilly and Company; National Institutes of Health [5T32HL069749-09] FX This analysis was sponsored by the Food and Drug Administration Office of Women's Health. TRANSLATE-ACS was funded by Daiichi Sankyo, Ltd and Eli Lilly and Company. Hess received support from the National Institutes of Health (grant 5T32HL069749-09). NR 39 TC 22 Z9 23 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD FEB PY 2014 VL 3 IS 1 AR e000523 DI 10.1161/JAHA.113.000523 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI3VZ UT WOS:000336794500017 PM 24510115 ER PT J AU Collinger, JL Kryger, MA Barbara, R Betler, T Bowsher, K Brown, EHP Clanton, ST Degenhart, AD Foldes, ST Gaunt, RA Gyulai, FE Harchick, EA Harrington, D Helder, JB Hemmes, T Johannes, MS Katyal, KD Ling, GSF McMorland, AJC Palko, K Para, MP Scheuermann, J Schwartz, AB Skidmore, ER Solzbacher, F Srikameswaran, AV Swanson, DP Swetz, S Tyler-Kabara, EC Velliste, M Wang, W Weber, DJ Wodlinger, B Boninger, ML AF Collinger, Jennifer L. Kryger, Michael A. Barbara, Richard Betler, Timothy Bowsher, Kristen Brown, Elke H. P. Clanton, Samuel T. Degenhart, Alan D. Foldes, Stephen T. Gaunt, Robert A. Gyulai, Ferenc E. Harchick, Elizabeth A. Harrington, Deborah Helder, John B. Hemmes, Timothy Johannes, Matthew S. Katyal, Kapil D. Ling, Geoffrey S. F. McMorland, Angus J. C. Palko, Karina Para, Matthew P. Scheuermann, Janet Schwartz, Andrew B. Skidmore, Elizabeth R. Solzbacher, Florian Srikameswaran, Anita V. Swanson, Dennis P. Swetz, Scott Tyler-Kabara, Elizabeth C. Velliste, Meel Wang, Wei Weber, Douglas J. Wodlinger, Brian Boninger, Michael L. TI Collaborative Approach in the Development of High-Performance Brain-Computer Interfaces for a Neuroprosthetic Arm: Translation from Animal Models to Human Control SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Article DE brain; clinical trials; methodology; translational research ID SPINAL-CORD-INJURY; ELECTROCORTICOGRAPHIC SPECTRAL-ANALYSIS; BLOCK AUTONOMIC HYPERREFLEXIA; HUMAN SENSORIMOTOR CORTEX; PRIMATE MOTOR CORTEX; ECOG SIGNALS; TRANSURETHRAL LITHOLAPAXY; MOVEMENT DIRECTION; CORTICAL CONTROL; PROSTHETIC ARM AB Our research group recently demonstrated that a person with tetraplegia could use a brain-computer interface (BCI) to control a sophisticated anthropomorphic robotic arm with skill and speed approaching that of an able-bodied person. This multiyear study exemplifies important principles in translating research from foundational theory and animal experiments into a clinical study. We present a roadmap that may serve as an example for other areas of clinical device research as well as an update on study results. Prior to conducting a multiyear clinical trial, years of animal research preceded BCI testing in an epilepsy monitoring unit, and then in a short-term (28 days) clinical investigation. Scientists and engineers developed the necessary robotic and surgical hardware, software environment, data analysis techniques, and training paradigms. Coordination among researchers, funding institutes, and regulatory bodies ensured that the study would provide valuable scientific information in a safe environment for the study participant. Finally, clinicians from neurosurgery, anesthesiology, physiatry, psychology, and occupational therapy all worked in a multidisciplinary team along with the other researchers to conduct a multiyear BCI clinical study. This teamwork and coordination can be used as a model for others attempting to translate basic science into real-world clinical situations. C1 [Collinger, Jennifer L.; Foldes, Stephen T.; Weber, Douglas J.; Boninger, Michael L.] Dept Vet Affairs Med Ctr, Pittsburgh, PA 15206 USA. [Collinger, Jennifer L.; Kryger, Michael A.; Barbara, Richard; Brown, Elke H. P.; Clanton, Samuel T.; Foldes, Stephen T.; Gaunt, Robert A.; Harchick, Elizabeth A.; Harrington, Deborah; Schwartz, Andrew B.; Skidmore, Elizabeth R.; Tyler-Kabara, Elizabeth C.; Wang, Wei; Weber, Douglas J.; Wodlinger, Brian; Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Collinger, Jennifer L.; Degenhart, Alan D.; Gaunt, Robert A.; Schwartz, Andrew B.; Tyler-Kabara, Elizabeth C.; Wang, Wei; Weber, Douglas J.; Boninger, Michael L.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Betler, Timothy; Srikameswaran, Anita V.] Univ Pittsburgh, Sch Hlth Sci Media Relat, Pittsburgh, PA USA. [Bowsher, Kristen] US FDA, Off Device Evaluat, Silver Spring, MD USA. [Degenhart, Alan D.; Foldes, Stephen T.; Schwartz, Andrew B.; Wang, Wei; Weber, Douglas J.; Wodlinger, Brian] Carnegie Mellon Univ, Ctr Neural Basis Cognit, Pittsburgh, PA 15213 USA. [Degenhart, Alan D.; Foldes, Stephen T.; Schwartz, Andrew B.; Wang, Wei; Weber, Douglas J.; Wodlinger, Brian] Univ Pittsburgh, Pittsburgh, PA USA. [Gyulai, Ferenc E.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA. [Helder, John B.; Johannes, Matthew S.; Katyal, Kapil D.; Para, Matthew P.; Swetz, Scott] Johns Hopkins Univ, Appl Phys Lab, Laurel, MD USA. [Ling, Geoffrey S. F.] Def Adv Res Projects Agcy, Arlington, VA USA. [McMorland, Angus J. C.; Schwartz, Andrew B.; Velliste, Meel] Univ Pittsburgh, Syst Neurosci Inst, Pittsburgh, PA USA. [McMorland, Angus J. C.; Schwartz, Andrew B.; Velliste, Meel] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA USA. [Schwartz, Andrew B.; Tyler-Kabara, Elizabeth C.; Boninger, Michael L.] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA USA. [Skidmore, Elizabeth R.] Univ Pittsburgh, Dept Occupat Therapy, Pittsburgh, PA USA. [Solzbacher, Florian] Univ Utah, Dept Elect & Comp Engn, Salt Lake City, UT USA. [Solzbacher, Florian] Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA. [Solzbacher, Florian] Univ Utah, Dept Mat Sci & Engn, Salt Lake City, UT 84112 USA. [Swanson, Dennis P.] Univ Pittsburgh, Res Conduct & Compliance Off, Pittsburgh, PA USA. [Tyler-Kabara, Elizabeth C.] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA. [Wang, Wei] Univ Pittsburgh, Clin & Translat Neurosci Inst, Pittsburgh, PA USA. RP Boninger, ML (reprint author), Dept Vet Affairs Med Ctr, Pittsburgh, PA 15206 USA. EM boninger@pitt.edu RI Tyler-Kabara, Elizabeth/H-4930-2013; OI Tyler-Kabara, Elizabeth/0000-0003-3286-1094; Gaunt, Robert/0000-0001-6202-5818; Boninger, Michael/0000-0001-6966-919X FU Defense Advanced Research Projects Agency (DARPA) Revolutionizing Prosthetics program [N66001-10-C-4056]; National Institutes of Health (NIH) [8KL2TR000146-07]; Office of Research and Development, Rehabilitation Research & Development Service, Department of Veterans Affairs [B6789C, B7143R, RX720]; UPMC Rehabilitation Institute FX This material is based upon work supported by the Defense Advanced Research Projects Agency (DARPA) Revolutionizing Prosthetics program contract number N66001-10-C-4056, the National Institutes of Health (NIH) grant 8KL2TR000146-07, the Office of Research and Development, Rehabilitation Research & Development Service, Department of Veterans Affairs (Grants # B6789C, B7143R, and RX720), and the UPMC Rehabilitation Institute. The views expressed herein are those of the authors and do not reflect the official policy or position of the Department of Veterans Affairs, Department of Defense, or the United States government. NR 64 TC 11 Z9 12 U1 1 U2 31 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 2014 VL 7 IS 1 BP 52 EP 59 DI 10.1111/cts.12086 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AA9VE UT WOS:000331440300015 PM 24528900 ER PT J AU Miller, HI AF Miller, Henry I. TI Investing in Bad Science SO POLICY REVIEW LA English DT Article C1 [Miller, Henry I.] Stanford Univ, Hoover Inst, Stanford, CA 94305 USA. [Miller, Henry I.] US FDA, Off Biotechnol, Rockville, MD 20857 USA. RP Miller, HI (reprint author), Stanford Univ, Hoover Inst, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU HOOVER INST PI STANFORD PA STANFORD UNIV, STANFORD, CA 94305-601 USA SN 0146-5945 J9 POLICY REV JI Policy Rev. PD FEB-MAR PY 2014 IS 177 BP 33 EP 42 PG 10 WC Political Science SC Government & Law GA AI1UO UT WOS:000336640800003 ER PT J AU Qi, YL Zhang, YT Fein, S Wang, CL Loyo-Berrios, N AF Qi, Youlin Zhang, Yuanting Fein, Sara Wang, Cunlin Loyo-Berrios, Nilsa TI Maternal and Breast Pump Factors Associated with Breast Pump Problems and Injuries SO JOURNAL OF HUMAN LACTATION LA English DT Article DE breast pump injuries; breastfeeding; breast pump; breastfeeding difficulties; breast pumping; breast pump problems ID BIRTH-WEIGHT INFANTS; FEEDING PRACTICES; UNITED-STATES; MOTHERS; MILK; CONTAMINATION; ANXIETY AB Background: Benefits of using a breast pump are well documented, but pump-related problems and injuries and the associated risk factors have not been reported. Objectives: This study aimed to describe breast pump-related problems and injuries and identify factors associated with these problems and injuries. Methods: Data were from the Infant Feeding Practices Study II; mothers were recruited from a nationally distributed consumer opinion panel. Mothers were asked about breast pump use, problems, and injuries at infant ages 2, 5, and 7 months. Survival analysis was used to identify factors associated with pump-related problems and injuries. Results: The sample included 1844 mothers. About 62% and 15% of mothers reported pump-related problems and injuries, respectively. The most commonly reported problem was that the pump did not extract enough milk and the most commonly reported injury was sore nipples. Using a battery-operated pump and intending to breastfeed less than 12 months were associated with higher risks of pump-related problems and injury. Learning from a friend to use the pump was associated with lower risk of pump-related problems, and using a manual pump and renting a pump were associated with a higher risk of problems. Conclusion: Our results suggest that problems and injuries associated with breast pump use can happen to mothers of all socioeconomic characteristics. Breastfeeding mothers may reduce their risks of problems and injury by not using battery-operated pumps and may reduce breast pump problems by not using manual pumps and by learning breast pump skills from a person rather than following written or video instructions. C1 [Qi, Youlin; Wang, Cunlin; Loyo-Berrios, Nilsa] US FDA, Silver Spring, MD 20993 USA. [Zhang, Yuanting; Fein, Sara] US FDA, College Pk, MD USA. RP Qi, YL (reprint author), US FDA, Ctr Devices & Radiol Hlth, WO66 RM4212,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM youlin.qi@fda.hhs.gov NR 24 TC 10 Z9 10 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0890-3344 EI 1552-5732 J9 J HUM LACT JI J. Hum. Lact. PD FEB PY 2014 VL 30 IS 1 BP 62 EP 72 DI 10.1177/0890334413507499 PG 11 WC Nursing; Obstetrics & Gynecology; Pediatrics SC Nursing; Obstetrics & Gynecology; Pediatrics GA AH1OP UT WOS:000335890900010 PM 24166052 ER PT J AU Pillai, SK Chang, A Murphy, MW Buzzell, J Ansari, A Whitcomb, RC Miller, C Jones, R Saunders, DP Cavicchia, P Watkins, SM Blackmore, C Williamson, JA Stephens, M Morrison, M McNees, J Murphree, R Buchanan, M Hogan, A Lando, J Nambiar, A Torso, L Melnic, JM Yang, L Lewis, L AF Pillai, Satish K. Chang, Arthur Murphy, Matthew W. Buzzell, Jennifer Ansari, Armin Whitcomb, Robert C., Jr. Miller, Charles Jones, Robert Saunders, David P. Cavicchia, Philip Watkins, Sharon M. Blackmore, Carina Williamson, John A. Stephens, Michael Morrison, Melissa McNees, James Murphree, Rendi Buchanan, Martha Hogan, Anthony Lando, James Nambiar, Atmaram Torso, Lauren Melnic, Joseph M. Yang, Lucie Lewis, Lauren TI 2011 Investigation of Internal Contamination with Radioactive Strontium Following Rubidium Rb 82 Cardiac PET Scan SO BIOSECURITY AND BIOTERRORISM-BIODEFENSE STRATEGY PRACTICE AND SCIENCE LA English DT Article AB During routine screening in 2011, US Customs and Border Protection (CBP) identified 2 persons with elevated radioactivity. CBP, in collaboration with Los Alamos National Laboratory, informed the Food and Drug Administration (FDA) that these people could have increased radiation exposure as a result of undergoing cardiac Positron Emission Tomography (PET) scans several months earlier with rubidium Rb 82 chloride injection from CardioGen-82. We conducted a multistate investigation to assess the potential extent and magnitude of radioactive strontium overexposure among patients who had undergone Rb 82 PET scans. We selected a convenience sample of clinical sites in 4 states and reviewed records to identify eligible study participants, defined as people who had had an Rb 82 PET scan between February and July 2011. All participants received direct radiation screening using a radioisotope identifier able to detect the gamma energy specific for strontium-85 (514keV) and urine bioassay for excreted radioactive strontium. We referred a subset of participants with direct radiation screening counts above background readings for whole body counting (WBC) using a rank ordering of direct radiation screening. The rank order list, from highest to lowest, was used to contact and offer voluntary enrollment for WBC. Of 308 participants, 292 (95%) had direct radiation screening results indistinguishable from background radiation measurements; 261 of 265 (98%) participants with sufficient urine for analysis had radioactive strontium results below minimum detectable activity. None of the 23 participants who underwent WBC demonstrated elevated strontium activity above levels associated with routine use of the rubidium Rb 82 generator. Among investigation participants, we did not identify evidence of strontium internal contamination above permissible levels. This investigation might serve as a model for future investigations of radioactive internal contamination incidents. C1 [Pillai, Satish K.; Chang, Arthur] Ctr Dis Control & Prevent, Hlth Studies Branch, Natl Ctr Environm Hlth, Atlanta, GA 30329 USA. [Murphy, Matthew W.; Ansari, Armin; Miller, Charles; Saunders, David P.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30329 USA. [Buzzell, Jennifer] Ctr Dis Control & Prevent, Radiat Studies Branch, Div Environm Hazards & Hlth Effects, Natl Ctr Environm Hlth, Atlanta, GA 30329 USA. [Whitcomb, Robert C., Jr.] Ctr Dis Control & Prevent, Radiat Studies Branch, Natl Ctr Environm Hlth, Atlanta, GA 30329 USA. [Jones, Robert] Ctr Dis Control & Prevent, Inorgan & Radiat Analyt Toxicol Branch, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA 30329 USA. [Lewis, Lauren] Ctr Dis Control & Prevent, Hlth Studies Branch, Div Environm Hazards & Hlth Effects, Natl Ctr Environm Hlth, Atlanta, GA 30329 USA. [Cavicchia, Philip] Florida Dept Hlth, Tallahassee, FL USA. [Watkins, Sharon M.; Blackmore, Carina] Florida Dept Hlth, Bur Epidemiol, Tallahassee, FL USA. [Stephens, Michael] Florida Dept Hlth, Florida Bur Radiat Control, Div Emergency Preparedness & Community Support, Tallahassee, FL USA. [Williamson, John A.] Florida Dept Hlth, Bur Radiat Control, Environm Radiat Programs, Orlando, FL USA. [Morrison, Melissa] CDC, Off Publ Hlth Preparedness & Response, Alabama Dept Publ Hlth, Ctr Emergency Preparedness, Montgomery, AL USA. [McNees, James] Alabama Dept Publ Hlth, Off Radiat Control, Montgomery, AL 36102 USA. [Murphree, Rendi] CDC, Tennessee Dept Hlth, Nashville, TN USA. [Buchanan, Martha] Knox Cty Hlt Dept, Knoxville, TN USA. [Hogan, Anthony] Tennessee Dept Environm & Conservat, Div Radiol Hlth, Nashville, TN USA. [Lando, James] CDC, Off Publ Hlth Preparedness & Response, Pittsburgh, PA USA. [Nambiar, Atmaram; Torso, Lauren] Dept Hlth, Div Infect Dis Epidemiol, Bur Epidemiol, Harrisburg, PA USA. [Melnic, Joseph M.] Bur Radiat Protect, Dept Environm Protect, Harrisburg, PA USA. [Yang, Lucie] US FDA, Div Nonprescript Clin Evaluat, Off New Drugs, Silver Spring, MD USA. RP Pillai, SK (reprint author), Ctr Dis Control & Prevent, NCEZID Div Preparedness & Emerging Infect, 1600 Clifton Rd,MS C18, Atlanta, GA 30329 USA. EM vig8@cdc.gov NR 15 TC 2 Z9 2 U1 1 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1538-7135 EI 1557-850X J9 BIOSECUR BIOTERROR JI Biosecur. Bioterror. PD FEB 1 PY 2014 VL 12 IS 1 BP 42 EP 48 DI 10.1089/bsp.2013.0072 PG 7 WC Public, Environmental & Occupational Health; International Relations SC Public, Environmental & Occupational Health; International Relations GA AB0EA UT WOS:000331463400005 PM 24552361 ER PT J AU Ramage, JG Prentice, KW Morse, SA Carter, AJ Datta, S Drumgoole, R Gargis, SR Griffin-Thomas, L Hastings, R Masri, HP Reed, MS Sharma, SK Singh, AK Swaney, E Swanson, T Gauthier, C Toney, D Pohl, J Shakamuri, P Stuchlik, O Elder, IA Estacio, PL Garber, EAE Hojvat, S Kellogg, RB Kovacs, G Stanker, L Weigel, L Hodge, DR Pillai, SP AF Ramage, Jason G. Prentice, Kristin Willner Morse, Stephen A. Carter, Andrew J. Datta, Shomik Drumgoole, Rahsaan Gargis, Shaw R. Griffin-Thomas, LaToya Hastings, Rebecca Masri, Heather P. Reed, Matthew S. Sharma, Shashi K. Singh, Ajay K. Swaney, Erin Swanson, Tanya Gauthier, Cheryl Toney, Denise Pohl, Jan Shakamuri, Priyanka Stuchlik, Olga Elder, Ian A. Estacio, Peter L. Garber, Eric A. E. Hojvat, Sally Kellogg, Richard B. Kovacs, Gerald Stanker, Larry Weigel, Linda Hodge, David R. Pillai, Segaran P. TI Comprehensive Laboratory Evaluation of a Specific Lateral Flow Assay for the Presumptive Identification of Abrin in Suspicious White Powders and Environmental Samples SO BIOSECURITY AND BIOTERRORISM-BIODEFENSE STRATEGY PRACTICE AND SCIENCE LA English DT Article ID RIBOSOME-INACTIVATING PROTEINS; LINKED-IMMUNOSORBENT-ASSAY; SITE-DIRECTED MUTAGENESIS; A A-CHAIN; ABRUS-PRECATORIUS; IN-VITRO; RICIN; AGGLUTININ; EXPRESSION; TOXICITY AB Abrin is a heterodimeric toxin present in the seeds of the Abrus precatorius plant. The easily obtainable seeds can yield a highly toxic product that can be used in various types of biocrimes and terrorism-related activities, including "white-powder" letters. Although the vast majority of these threats are hoaxes, the lack of rapid and reliable detection assays for abrin, such as lateral flow assays (LFAs), can be an impediment to accurate and rapid hazard assessment. One of the complicating factors associated with LFAs is the use of antibodies of poor affinity and specificity that cross-react with near neighbors or that bind to plant lectins, which are capable of nonspecifically cross-linking the capture and detector antibodies. Because of the critical need to promote public safety and public health, we conducted a comprehensive laboratory evaluation of a commercial LFA for the rapid detection of abrin. This study was conducted using comprehensive inclusivity and exclusivity panels of abrin and near-neighbor plant materials, along with panels of lectins, related proteins, white powders, and environmental background material, to determine the sensitivity, specificity, limit of detection, dynamic range, and repeatability of the assay for the specific intended use of evaluating suspicious white powders and environmental samples for the presumptive presence of abrin. C1 [Ramage, Jason G.; Prentice, Kristin Willner] Booz Allen Hamilton Inc, Mclean, VA USA. [Hodge, David R.; Pillai, Segaran P.] US Dept Homeland Secur, Chem & Biol Def Div, Sci & Technol Directorate, Washington, DC 20528 USA. [Morse, Stephen A.; Carter, Andrew J.] Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA USA. [Datta, Shomik; Sharma, Shashi K.; Singh, Ajay K.; Garber, Eric A. E.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Drumgoole, Rahsaan; Swaney, Erin] Texas Dept State Hlth Serv, Emergency Preparedness Branch, Austin, TX USA. [Gargis, Shaw R.] CDC, Div Select Agents & Toxins, Atlanta, GA 30333 USA. [Griffin-Thomas, LaToya; Masri, Heather P.; Toney, Denise] Div Consolidated Lab Serv, Richmond, VA USA. [Hastings, Rebecca; Swanson, Tanya; Gauthier, Cheryl] Massachusetts Dept Publ Hlth, State Lab Inst, Bioterrorism Response Lab, Jamaica Plain, MA USA. [Reed, Matthew S.; Shakamuri, Priyanka] CDC, Div Sci Resources, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA. [Pohl, Jan] CDC, Biotechnol Core Facil Branch, Div Sci Resources, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA. [Elder, Ian A.] US Dept Homeland Secur, Washington, DC USA. [Estacio, Peter L.] Lawrence Livermore Natl Lab, Livermore, CA USA. [Hojvat, Sally] US FDA, Div Microbiol Devices, Silver Spring, MD USA. [Kellogg, Richard B.; Weigel, Linda] CDC, Lab Preparedness & Response Branch, Div Preparedness & Emerging Infect, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA. [Kovacs, Gerald] ABL Inc, Rockville, MD USA. [Stanker, Larry] USDA ARS, Foodborne Toxin Detect & Control Res Unit, Albany, CA USA. RP Pillai, SP (reprint author), US Dept Homeland Secur, Chem & Biol Def Div, Sci & Technol Directorate, Washington, DC 20528 USA. EM Segaran.Pillai@HQ.DHS.GOV NR 33 TC 6 Z9 6 U1 1 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1538-7135 EI 1557-850X J9 BIOSECUR BIOTERROR JI Biosecur. Bioterror. PD FEB 1 PY 2014 VL 12 IS 1 BP 49 EP 62 DI 10.1089/bsp.2013.0080 PG 14 WC Public, Environmental & Occupational Health; International Relations SC Public, Environmental & Occupational Health; International Relations GA AB0EA UT WOS:000331463400006 PM 24552362 ER PT J AU Alsante, KM Huynh-Ba, KC Baertschi, SW Reed, RA Landis, MS Furness, S Olsen, B Mowery, M Russo, K Iser, R Stephenson, GA Jansen, P AF Alsante, Karen M. Huynh-Ba, Kim C. Baertschi, Steven W. Reed, Robert A. Landis, Margaret S. Furness, Scott Olsen, Bernard Mowery, Mark Russo, Karen Iser, Robert Stephenson, Gregory A. Jansen, Patrick TI Recent Trends in Product Development and Regulatory Issues on Impurities in Active Pharmaceutical Ingredient (API) and Drug Products. Part 2: Safety Considerations of Impurities in Pharmaceutical Products and Surveying the Impurity Landscape SO AAPS PHARMSCITECH LA English DT Article ID SOLID-STATE; DEGRADATION; PHOTOSTABILITY; REACTIVITY; IDENTIFICATION; HYDROCHLORIDE; ACETONITRILE; AUTOXIDATION; FORMULATION; SUBSTANCES C1 [Alsante, Karen M.; Landis, Margaret S.] Pfizer Global Res & Dev, Groton, CT 06340 USA. [Huynh-Ba, Kim C.] Pharmalytik Newark, Newark, DE USA. [Baertschi, Steven W.; Stephenson, Gregory A.; Jansen, Patrick] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Reed, Robert A.] Celsion Corp, Lawrenceville, NJ USA. [Furness, Scott; Iser, Robert] US FDA, Washington, DC 20204 USA. [Olsen, Bernard] Olsen Pharmaceut Consulting LLC, W Lafayette, IN USA. [Mowery, Mark] Merck & Co Inc, West Point, PA USA. [Russo, Karen] US Pharmacopeial Convent Inc, Rockville, MD USA. RP Landis, MS (reprint author), Pfizer Global Res & Dev, Groton, CT 06340 USA. EM margaret.s.landis@pfizer.com NR 75 TC 3 Z9 3 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PD FEB PY 2014 VL 15 IS 1 BP 237 EP 251 DI 10.1208/s12249-013-0061-z PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AE5TW UT WOS:000334053200025 PM 24363207 ER PT J AU Zhou, WL Wang, PG AF Zhou, Wanlong Wang, Perry G. TI Cosmetic bioanalysis using LC-MS: challenges and future outlook SO BIOANALYSIS LA English DT Editorial Material DE carryover; cosmetics; LC-MS; matrix effects; weighting factor ID MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; HEXAPEPTIDES C1 [Zhou, Wanlong; Wang, Perry G.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. RP Wang, PG (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM perry.wang@fda.hhs.gov NR 10 TC 0 Z9 0 U1 2 U2 7 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 EI 1757-6199 J9 BIOANALYSIS JI Bioanalysis PD FEB PY 2014 VL 6 IS 4 BP 437 EP 440 DI 10.4155/bio.13.246 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA AC6IY UT WOS:000332626700008 PM 24568347 ER PT J AU Williamson, LN Conner, DP Stier, EM Davit, BM AF Williamson, Leah N. Conner, Dale P. Stier, Ethan M. Davit, Barbara M. TI Common bioanalytical deficiencies with bioequivalence submissions in Abbreviated New Drug Applications SO BIOANALYSIS LA English DT Article AB Background: The US FDA published A Guidance for Industry: Bioanalytical Method Validation in May 2001. Despite the publication of the guidance, companies continue to submit bioequivalence studies with bioanalytical deficiencies that preclude Abbreviated New Drug Application approval. The Divisions of Bioequivalence in the FDA's Office of Generic Drugs conducted a survey of the bioequivalence submissions over a 10-year period (2001-2011) to identify the most commonly occurring bioanalytical deficiencies. Results: Data from a total of 4028 Abbreviated New Drug Application submissions were collected to identify bioanalytical deficiencies. Of the three categories of bioanalytical deficiencies (method, validation and report), the majority of the deficiencies were from the bioanalytical method validation section. Globally, the percentage of bioanalytical method validation deficiencies was 62%. Conclusions: The approval of generic drugs would be accelerated if these deficiencies were avoided by generic companies by adhering to the guidance and therefore submitting a more complete application. C1 [Williamson, Leah N.; Conner, Dale P.; Stier, Ethan M.] US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, MD 20852 USA. [Davit, Barbara M.] Merck Res Labs, Rahway, NJ 07065 USA. RP Williamson, LN (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, 11919 Rockville Pike, Rockville, MD 20852 USA. EM leah.williamson@fda.hhs.gov NR 1 TC 0 Z9 0 U1 2 U2 6 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 EI 1757-6199 J9 BIOANALYSIS JI Bioanalysis PD FEB PY 2014 VL 6 IS 4 BP 441 EP 445 DI 10.4155/bio.13.329 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA AC6IY UT WOS:000332626700009 PM 24568348 ER PT J AU Yu, CW Bashaw, ED AF Yu, Chongwoo Bashaw, Edward D. TI Regulatory perspective of bioana-lysis from a clinical pharmacology reviewer standpoint: do you see what I see? SO BIOANALYSIS LA English DT Article ID TESTOSTERONE AB Clinical pharmacology plays an important role in drug development, including the evaluation of the drugs pharmacokinetics, pharmacodynamics, drug-interaction potential, exposure-response relationship and safety considerations when being used in specific populations. Clinical pharmacology data is pivotal in ensuring the delivery of the right drug, in the right dose, at the right time, to each particular patient and it has significantly influenced the risk/benefit assessment and labeling recommendations. Consequently, the reliability of the bioanalytical methods and data are of considerable importance, and the solid footing in drug development. Documentation of bioanalytical data from method validation or clinical trials is a critical element supporting regulatory submissions such as new drug applications or biologics license applications. Case examples are presented to highlight the utility and importance of bioanalysis in drug development to ensure that drug products are safe, efficacious, and given at the right dose. C1 [Yu, Chongwoo; Bashaw, Edward D.] US FDA, Div Clin Pharmacol 3, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Yu, CW (reprint author), US FDA, Div Clin Pharmacol 3, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM chongwoo.yu@fda.hhs.gov NR 8 TC 1 Z9 1 U1 0 U2 3 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 EI 1757-6199 J9 BIOANALYSIS JI Bioanalysis PD FEB PY 2014 VL 6 IS 4 BP 505 EP 510 DI 10.4155/bio.13.334 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA AC6IY UT WOS:000332626700015 PM 24568353 ER PT J AU Toro, M Cao, GJ Ju, WT Allard, M Barrangou, R Zhao, SH Brown, E Meng, JH AF Toro, Magaly Cao, Guojie Ju, Wenting Allard, Marc Barrangou, Rodolphe Zhao, Shaohua Brown, Eric Meng, Jianghong TI Association of Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) Elements with Specific Serotypes and Virulence Potential of Shiga Toxin-Producing Escherichia coli SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID REAL-TIME PCR; CAS SYSTEMS; STREPTOCOCCUS-THERMOPHILUS; ANTIVIRAL DEFENSE; IMMUNE-SYSTEM; EVOLUTION; RESISTANCE; INTERFERENCE; PROKARYOTES; STRAINS AB Shiga toxin-producing Escherichia coli (STEC) strains (n = 194) representing 43 serotypes and E. coli K-12 were examined for clustered regularly interspaced short palindromic repeat (CRISPR) arrays to study genetic relatedness among STEC serotypes. A subset of the strains (n = 81) was further analyzed for subtype I-E cas and virulence genes to determine a possible association of CRISPR elements with potential virulence. Four types of CRISPR arrays were identified. CRISPR1 and CRISPR2 were present in all strains tested; 1 strain also had both CRISPR3 and CRISPR4, whereas 193 strains displayed a short, combined array, CRISPR3-4. A total of 3,353 spacers were identified, representing 528 distinct spacers. The average length of a spacer was 32 bp. Approximately one-half of the spacers (54%) were unique and found mostly in strains of less common serotypes. Overall, CRISPR spacer contents correlated well with STEC serotypes, and identical arrays were shared between strains with the same H type (O26:H11, O103:H11, and O111:H11). There was no association identified between the presence of subtype I-E cas and virulence genes, but the total number of spacers had a negative correlation with potential pathogenicity (P < 0.05). Fewer spacers were found in strains that had a greater probability of causing outbreaks and disease than in those with lower virulence potential (P < 0.05). The relationship between the CRISPR-cas system and potential virulence needs to be determined on a broader scale, and the biological link will need to be established. C1 [Toro, Magaly; Cao, Guojie; Ju, Wenting; Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Toro, Magaly; Cao, Guojie; Meng, Jianghong] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Allard, Marc; Brown, Eric] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Barrangou, Rodolphe] N Carolina State Univ, Dept Food Bioproc & Nutr Sci, Raleigh, NC 27695 USA. [Zhao, Shaohua] US FDA, Ctr Vet Med, Laurel, MD USA. RP Meng, JH (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. EM jmeng@umd.edu RI Toro, Magaly/F-6525-2011; Barrangou, Rodolphe/I-2878-2014 OI Toro, Magaly/0000-0002-6280-2215; Barrangou, Rodolphe/0000-0002-0648-3504 NR 45 TC 16 Z9 16 U1 0 U2 19 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 FEB PY 2014 VL 80 IS 4 BP 1411 EP 1420 DI 10.1128/AEM.03018-13 PG 10 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA AB2LV UT WOS:000331625100021 PM 24334663 ER PT J AU Napier, ID Simon, L Perry, D Cooke, PS Stocco, DM Sepehr, E Doerge, DR Kemppainen, BW Morrison, EE Akingbemi, BT AF Napier, India D. Simon, Liz Perry, Devin Cooke, Paul S. Stocco, Douglas M. Sepehr, Estatira Doerge, Daniel R. Kemppainen, Barbara W. Morrison, Edward E. Akingbemi, Benson T. TI Testicular Development in Male Rats Is Sensitive to a Soy-Based Diet in the Neonatal Period SO BIOLOGY OF REPRODUCTION LA English DT Article DE androgen; androgens/androgen receptor; daidzein; endocrine disruptors; genistein; Leydig cells; phytoestrogen; sex steroids; testis; toxicology ID SPRAGUE-DAWLEY RATS; ANTI-MULLERIAN HORMONE; LEYDIG-CELLS; TESTOSTERONE LEVELS; BISPHENOL-A; STEROIDOGENIC ENZYMES; LACTATIONAL TRANSFER; LUTEINIZING-HORMONE; INFANT FORMULA; DEFICIENT MICE AB Approximately 30% of infants in the United States are exposed to high doses of isoflavones resulting from soy infant formula consumption. Soybeans contain the isoflavones genistin and daidzin, which are hydrolyzed in the gastrointestinal tract to their genistein and daidzein aglycones. Both aglycones possess hormonal activity and may interfere with male reproductive development. Testosterone, which supports male fertility, is mainly produced by testicular Leydig cells. Our previous studies indicated that perinatal exposure of male rats to isoflavones induced proliferative activity in Leydig cells and increased testosterone concentrations into adulthood. However, the relevance of the neonatal period as part of the perinatal window of isoflavone exposure remains to be established. The present study examined the effects of exposure to isoflavones on male offspring of dams maintained on a casein-based control or whole soybean diet in the neonatal period, that is, Days 2 to 21 postpartum. The results showed that the soybean diet stimulated proliferative activity in developing Leydig cells while suppressing their steroidogenic capacity in adulthood. In addition, isoflavone exposure decreased production of anti-Mullerian hormone by Sertoli cells. Similar to our previous in vitro studies of genistein action in Leydig cells, daidzein induced proliferation and interfered with signaling pathways to suppress steroidogenic activity. Overall, the data showed that the neonatal period is a sensitive window of exposure to isoflavones and support the view that both genistein and daidzein are responsible for biological effects associated with soy-based diets. C1 [Napier, India D.; Perry, Devin; Kemppainen, Barbara W.; Morrison, Edward E.; Akingbemi, Benson T.] Auburn Univ, Dept Anat Physiol & Pharmacol, Auburn, AL 36849 USA. [Simon, Liz] Louisiana State Univ, Hlth Sci Ctr, Dept Physiol, New Orleans, LA USA. [Cooke, Paul S.] Univ Florida, Dept Physiol Sci, Gainesville, FL 32610 USA. [Stocco, Douglas M.] Texas Tech Univ, Hlth Sci Ctr, Dept Cell Biol & Biochem, Lubbock, TX 79409 USA. [Sepehr, Estatira; Doerge, Daniel R.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Akingbemi, BT (reprint author), Auburn Univ, Dept Anat Physiol & Pharmacol, Auburn, AL 36849 USA. EM akingbt@auburn.edu FU National Institutes of Health [ES 15886]; Oak Ridge Institute for Science and Education, administered through an interagency agreement between the U.S. Department of Energy; U.S. Food and Drug Administration FX Supported in part by National Institutes of Health grant ES 15886 to B.T.A. E.S. was supported by 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 views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. Data were presented in preliminary form at the 46th Annual Meeting of the Society for the Study of Reproduction, July 31-August 4, 2011, Portland OR. NR 56 TC 4 Z9 5 U1 2 U2 17 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 EI 1529-7268 J9 BIOL REPROD JI Biol. Reprod. PD FEB PY 2014 VL 90 IS 2 DI 10.1095/biolreprod.113.113787 PG 12 WC Reproductive Biology SC Reproductive Biology GA AC6HO UT WOS:000332622400008 PM 24451983 ER PT J AU Baxi, J Calhoun, W Sepah, YJ Hammer, DX Ilev, I Pfefer, TJ Nguyen, QD Agrawal, A AF Baxi, Jigesh Calhoun, William Sepah, Yasir Jamal Hammer, Daniel X. Ilev, Ilko Pfefer, T. Joshua Quan Dong Nguyen Agrawal, Anant TI Retina-simulating phantom for optical coherence tomography SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE phantoms; optical coherence tomography; tissue-mimicking phantoms; optical coherence tomography measurements ID OCT DEVICES; MODEL EYE; THICKNESS; PERFORMANCE AB Optical coherence tomography (OCT) is a rapidly growing imaging modality, particularly in the field of ophthalmology. Accurate early diagnosis of diseases requires consistent and validated imaging performance. In contrast to more well-established medical imaging modalities, no standardized test methods currently exist for OCT quality assurance. We developed a retinal phantom which mimics the thickness and near-infrared optical properties of each anatomical retinal layer as well as the surface topography of the foveal pit. The fabrication process involves layer-by-layer spin coating of nanoparticle-embedded silicone films followed by laser micro-etching to modify the surface topography. The thickness of each layer and dimensions of the foveal pit are measured with high precision. The phantom is embedded into a commercially available, water-filled model eye to simulate ocular dispersion and emmetropic refraction, and for ease of use with clinical OCT systems. The phantom was imaged with research and clinical OCT systems to assess image quality and software accuracy. Our results indicate that this phantom may serve as a useful tool to evaluate and standardize OCT performance. (C) The Authors. C1 [Baxi, Jigesh; Calhoun, William; Hammer, Daniel X.; Ilev, Ilko; Pfefer, T. Joshua; Agrawal, Anant] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20933 USA. [Sepah, Yasir Jamal; Quan Dong Nguyen] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Retinal Imaging Res & Reading Ctr, Baltimore, MD 21287 USA. [Sepah, Yasir Jamal; Quan Dong Nguyen] Univ Nebraska Med Ctr, Stanley M Truhlsen Eye Inst, Omaha, NE 68131 USA. RP Baxi, J (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20933 USA. EM Jigesh.Baxi@fda.hhs.gov FU US Food and Drug Administration's Critical Path Initiative FX The research in this publication was supported by the US Food and Drug Administration's Critical Path Initiative. 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 28 TC 14 Z9 15 U1 5 U2 64 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 FEB PY 2014 VL 19 IS 2 AR 021106 DI 10.1117/1.JBO.19.2.021106 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AC9CE UT WOS:000332830900008 PM 24042445 ER PT J AU Yu, Y Fuscoe, JC Zhao, C Guo, C Jia, MW Qing, T Bannon, DI Lancashire, L Bao, WJ Du, TT Luo, H Su, ZQ Jones, WD Moland, CL Branham, WS Qian, F Ning, BT Li, Y Hong, HX Guo, L Mei, N Shi, TL Wang, KY Wolfinger, RD Nikolsky, Y Walker, SJ Duerksen-Hughes, P Mason, CE Tong, WD Thierry-Mieg, J Thierry-Mieg, D Shi, LM Wang, C AF Yu, Ying Fuscoe, James C. Zhao, Chen Guo, Chao Jia, Meiwen Qing, Tao Bannon, Desmond I. Lancashire, Lee Bao, Wenjun Du, Tingting Luo, Heng Su, Zhenqiang Jones, Wendell D. Moland, Carrie L. Branham, William S. Qian, Feng Ning, Baitang Li, Yan Hong, Huixiao Guo, Lei Mei, Nan Shi, Tieliu Wang, Kevin Y. Wolfinger, Russell D. Nikolsky, Yuri Walker, Stephen J. Duerksen-Hughes, Penelope Mason, Christopher E. Tong, Weida Thierry-Mieg, Jean Thierry-Mieg, Danielle Shi, Leming Wang, Charles TI A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages SO NATURE COMMUNICATIONS LA English DT Article ID MOUSE GENE-EXPRESSION; GENOME; LIVER; IDENTIFICATION; INFORMATION; LANDSCAPE; MODENCODE; ELEMENTS; DATABASE; DISEASE AB The rat has been used extensively as a model for evaluating chemical toxicities and for understanding drug mechanisms. However, its transcriptome across multiple organs, or developmental stages, has not yet been reported. Here we show, as part of the SEQC consortium efforts, a comprehensive rat transcriptomic BodyMap created by performing RNA-Seq on 320 samples from 11 organs of both sexes of juvenile, adolescent, adult and aged Fischer 344 rats. We catalogue the expression profiles of 40,064 genes, 65,167 transcripts, 31,909 alternatively spliced transcript variants and 2,367 non-coding genes/non-coding RNAs (ncRNAs) annotated in AceView. We find that organ-enriched, differentially expressed genes reflect the known organ-specific biological activities. A large number of transcripts show organ-specific, age-dependent or sex-specific differential expression patterns. We create a web-based, open-access rat BodyMap database of expression profiles with crosslinks to other widely used databases, anticipating that it will serve as a primary resource for biomedical research using the rat model. C1 [Yu, Ying; Zhao, Chen; Jia, Meiwen; Qing, Tao; Du, Tingting; Luo, Heng; Shi, Leming] Fudan Univ, Sch Life Sci & Pharm, Ctr Pharmacogen, State Key Lab Genet Engn, Shanghai 201203, Peoples R China. [Yu, Ying; Zhao, Chen; Jia, Meiwen; Qing, Tao; Du, Tingting; Luo, Heng; Shi, Leming] Fudan Univ, Sch Life Sci & Pharm, MOE Key Lab Contemporary Anthropol, Shanghai 201203, Peoples R China. [Fuscoe, James C.; Su, Zhenqiang; Moland, Carrie L.; Branham, William S.; Qian, Feng; Ning, Baitang; Li, Yan; Hong, Huixiao; Guo, Lei; Mei, Nan; Tong, Weida; Shi, Leming] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 92079 USA. [Bannon, Desmond I.] Army Inst Publ Hlth, US Army Publ Hlth Command, Aberdeen Proving Ground, MD 21010 USA. [Lancashire, Lee] IP & Sci Thomson Reuters, London EC1N 8JS, England. [Bao, Wenjun; Wolfinger, Russell D.] SAS Inst Inc, Cary, NC 27513 USA. [Jones, Wendell D.] Express Anal Inc, Durham, NC 27713 USA. [Shi, Tieliu] Coll Life Sci, Ctr Bioinformat, Shanghai 200241, Peoples R China. [Shi, Tieliu] Coll Life Sci, Inst Biomed Sci, Shanghai 200241, Peoples R China. [Wang, Kevin Y.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [Walker, Stephen J.] Wake Forest Univ Hlth Sci, Wake Forest Inst Regenerat Med, Winston Salem, NC 27157 USA. [Duerksen-Hughes, Penelope] Loma Linda Univ, Sch Med, Dept Basic Sci, Loma Linda, CA 92350 USA. [Mason, Christopher E.] Cornell Univ, Dept Physiol & Biophys, New York, NY 10021 USA. [Mason, Christopher E.] Cornell Univ, Inst Computat Biomed, New York, NY 10021 USA. [Thierry-Mieg, Jean; Thierry-Mieg, Danielle] Natl Inst Hlth, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Shi, Leming] Fudan Zhangjiang Ctr Clin Genom, Shanghai 201203, Peoples R China. [Shi, Leming] Zhangjiang Ctr Translat Med, Shanghai 201203, Peoples R China. [Wang, Charles] Loma Linda Univ, Sch Med, Ctr Genom & Div Microbiol Mol Genet, Loma Linda, CA 92350 USA. RP Wang, C (reprint author), Loma Linda Univ, Sch Med, Ctr Genom & Div Microbiol Mol Genet, Loma Linda, CA 92350 USA. EM leming.shi@gmail.com; oxwang@gmail.com RI Guo, Chao/B-2647-2010; mei, nan/E-8915-2011; Luo, Heng/D-3616-2016; THIERRY-MIEG, Jean/F-1975-2017 OI Guo, Chao/0000-0002-6673-0933; mei, nan/0000-0002-3501-9014; Luo, Heng/0000-0001-5192-8878; THIERRY-MIEG, Jean/0000-0002-0396-6789 FU US Food and Drug Administrative Agency (FDA); FDA Office of Women's Health, China's Program of Global Experts; National Institutes of Health's (NIH) Intramural Research Program; National 973 Key Basic Research Program of China [2010CB945401]; National Natural Science Foundation of China [31240038, 31071162]; Science and Technology Commission of Shanghai Municipality [11DZ2260300]; China's National Super-computing Center of Tianjin; NIH/NCBI's Supercomputing Center; USA FDA's Supercomputing Center FX The views presented in this article do not necessarily reflect current or future opinion or policy of the US Food and Drug Administration. Any mention of commercial products is for clarification and not intended as an endorsement. This work was supported in part by the US Food and Drug Administrative Agency (FDA), the FDA Office of Women's Health, China's Program of Global Experts, the National Institutes of Health's (NIH) Intramural Research Program, the National 973 Key Basic Research Program of China (2010CB945401), the National Natural Science Foundation of China (31240038 and 31071162) and the Science and Technology Commission of Shanghai Municipality (11DZ2260300). We gratefully acknowledge support by the China's National Super-computing Center of Tianjin, the NIH/NCBI's Supercomputing Center and the USA FDA's Supercomputing Center. We also thank Drs. Keely Walker, David Klein, Marina Bessarabova and Donna Mendrick for critical review of an earlier version of the manuscript. NR 43 TC 50 Z9 52 U1 1 U2 39 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD FEB PY 2014 VL 5 AR 3230 DI 10.1038/ncomms4230 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AC6WG UT WOS:000332665700005 PM 24510058 ER PT J AU Alam, MM Bufano, MK Xu, P Kalsy, A Yu, Y Freeman, YW Sultana, T Rashu, MR Desai, I Eckhoff, G Leung, DT Charles, RC LaRocque, RC Harris, JB Clements, JD Calderwood, SB Qadri, F Vann, WF Kovac, P Ryan, ET AF Alam, Mohammad Murshid Bufano, Megan Kelly Xu, Peng Kalsy, Anuj Yu, Y. Freeman, Y. Wu Sultana, Tania Rashu, Md. Rasheduzzaman Desai, Ishaan Eckhoff, Grace Leung, Daniel T. Charles, Richelle C. LaRocque, Regina C. Harris, Jason B. Clements, John D. Calderwood, Stephen B. Qadri, Firdausi Vann, W. F. Kovac, Pavol Ryan, Edward T. TI Evaluation in Mice of a Conjugate Vaccine for Cholera Made from Vibrio cholerae O1 (Ogawa) O-Specific Polysaccharide SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID MEMORY B-CELL; INFECTION-DERIVED IMMUNITY; ORAL KILLED CHOLERA; FREE MOUSE MODEL; ANTIBODY-RESPONSES; SEROTYPE OGAWA; DETOXIFIED LIPOPOLYSACCHARIDE; TRANSCUTANEOUS IMMUNIZATION; PROTECTIVE IMMUNITY; HOUSEHOLD CONTACTS AB Background Protective immunity against cholera is serogroup specific. Serogroup specificity in Vibrio cholerae is determined by the O-specific polysaccharide (OSP) of lipopolysaccharide (LPS). Generally, polysaccharides are poorly immunogenic, especially in young children. Methodology Here we report the evaluation in mice of a conjugate vaccine for cholera (OSP:TThc) made from V. cholerae O1 Ogawa O-Specific Polysaccharide-core (OSP) and recombinant tetanus toxoid heavy chain fragment (TThc). We immunized mice intramuscularly on days 0, 21, and 42 with OSP:TThc or OSP only, with or without dmLT, a non-toxigenic immunoadjuvant derived from heat labile toxin of Escherichia coli. Principal Findings We detected significant serum IgG antibody responses targeting OSP following a single immunization in mice receiving OSP:TThc with or without adjuvant. Anti-LPS IgG responses were detected following a second immunization in these cohorts. No anti-OSP or anti-LPS IgG responses were detected at any time in animals receiving un-conjugated OSP with or without immunoadjuvant, and in animals receiving immunoadjuvant alone. Responses were highest following immunization with adjuvant. Serum anti-OSP IgM responses were detected in mice receiving OSP:TThc with or without immunoadjuvant, and in mice receiving unconjugated OSP. Serum anti-LPS IgM and vibriocidal responses were detected in all vaccine cohorts except in mice receiving immunoadjuvant alone. No significant IgA anti-OSP or anti-LPS responses developed in any group. Administration of OSP:TThc and adjuvant also induced memory B cell responses targeting OSP and resulted in 95% protective efficacy in a mouse lethality cholera challenge model. Conclusion We describe a protectively immunogenic cholera conjugate in mice. Development of a cholera conjugate vaccine could assist in inducing long-term protective immunity, especially in young children who respond poorly to polysaccharide antigens. Author Summary Cholera is a severe dehydrating diarrheal illness of humans caused by organisms Vibrio cholerae serogroups O1 or O139 serogroup organisms. Protective immunity against cholera is serogroup specific. Serogroup specificity in V. cholerae is determined by the O-specific polysaccharide (OSP) of lipopolysaccharide (LPS). Generally, polysaccharides are poorly immunogenic, especially in young children. Unfortunately, children bear a large burden of cholera globally. Here we describe a novel cholera conjugate vaccine and show that it induces immune responses in mice, including memory responses, to OSP, the T cell-independent antigen that probably is the target of protective immunity to cholera. These responses were highest following immunization of the vaccine with a novel immunoadjuvant, dmLT. We also show that immunization of mice with this conjugate vaccine protects against challenge with wild-type V. cholerae. A protectively immunogenic cholera conjugate vaccine that induces long-term memory responses could have particular utility in young children who are most at risk of cholera. C1 [Alam, Mohammad Murshid; Bufano, Megan Kelly; Kalsy, Anuj; Yu, Y.; Freeman, Y. Wu; Sultana, Tania; Rashu, Md. Rasheduzzaman; Desai, Ishaan; Eckhoff, Grace; Leung, Daniel T.; Charles, Richelle C.; LaRocque, Regina C.; Harris, Jason B.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Alam, Mohammad Murshid; Sultana, Tania; Rashu, Md. Rasheduzzaman; Leung, Daniel T.; Qadri, Firdausi] ICDDR B, Dhaka, Bangladesh. [Xu, Peng; Kovac, Pavol] NIDDK, LBC, NIH, Bethesda, MD 20892 USA. [Leung, Daniel T.; Charles, Richelle C.; LaRocque, Regina C.; Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Clements, John D.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA USA. [Vann, W. F.] US FDA, CBER, Lab Bacterial Toxins, Bethesda, MD 20014 USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Alam, MM (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM etryan@partners.org RI Kovac, Pavol/B-8813-2008; Xu, Peng/K-7036-2012; OI Kovac, Pavol/0000-0001-5044-3449; leung, daniel/0000-0001-8401-0801 FU icddr,b; Intramural Research Program of the National Institutes of Health; NIDDK; National Institutes of Health; National Institute of Allergy & Infectious Diseases [AI077883, AI106878, AI058935]; career development awards [K08 AI089721, K08 AI100923]; Fogarty International Center Training Grant in Vaccine Development and Public Health [TW005572]; FIC Career Development Awards [K01 TW07409, TW07144]; Swedish International Development Cooperation Agency; Howard Hughes Medical Institute; American Society for Tropical Medicine & Hygiene - Burroughs Wellcome Fund FX This research was supported by the icddr,b, by the Intramural Research Program of the National Institutes of Health, NIDDK, and extramural grants from the National Institutes of Health, including the National Institute of Allergy & Infectious Diseases (AI077883, AI106878, AI058935 [SBC, ETR, and FQ], and career development awards K08 AI089721 [RCC] and K08 AI100923 [DTL]), a Fogarty International Center Training Grant in Vaccine Development and Public Health (TW005572 [MMA, TS, MRR and FQ]), FIC Career Development Awards (K01 TW07409 [JBH], TW07144 [RCL]), as well as by the Swedish International Development Cooperation Agency (FQ), a Physician Scientist Early Career Award from the Howard Hughes Medical Institute (RCL), and a Postdoctoral Fellowship in Tropical Infectious Diseases from the American Society for Tropical Medicine & Hygiene - Burroughs Wellcome Fund (DTL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 62 TC 5 Z9 5 U1 1 U2 7 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 2014 VL 8 IS 2 AR e2683 DI 10.1371/journal.pntd.0002683 PG 8 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AB8CK UT WOS:000332017500019 PM 24516685 ER PT J AU Gannavaram, S Davey, S Lakhal-Naouar, I Duncan, R Nakhasi, HL AF Gannavaram, Sreenivas Davey, Sonya Lakhal-Naouar, Ines Duncan, Robert Nakhasi, Hira L. TI Deletion of Ubiquitin Fold Modifier Protein Ufm1 Processing Peptidase Ufsp in L. donovani Abolishes Ufm1 Processing and Alters Pathogenesis SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID LEISHMANIA-DONOVANI; PLASMODIUM-FALCIPARUM; VISCERAL LEISHMANIASIS; TRYPANOSOMA-BRUCEI; IDENTIFICATION; SYSTEM; AMASTIGOTES; NUCLEASE; ENZYME AB Previously, we showed Leishmania donovani Ufm1 has a Gly residue conserved at the C-terminal region with a unique 17 amino acid residue extension that must be processed prior to conjugation to target proteins. In this report, we describe for the first time the isolation and characterization of the Leishmania Ufm1-specific protease Ufsp. Biochemical analysis of L. donovani Ufsp showed that this protein possesses the Ufm1 processing activity using sensitive FRET based activity probes. The Ufm1 cleavage activity was absent in a mutant Ufsp in which the active site cysteine is altered to a serine. To examine the effects of abolition of Ufm1 processing activity, we generated a L. donovani null mutant of Ufsp (LdUfsp(-/-)). Ufm1 processing activity was abolished in LdUfsp(-/-) mutant, and the processing defect was reversed by re-expression of wild type but not the cys>ser mutant in the LdUfsp(-/-) parasites. Further LdUfsp(-/-) mutants showed reduced survival as amastigotes in infected human macrophages but not as promastigotes. This growth defect in the amastigotes was reversed by re-expression of wild type but not the cys>ser mutant in the Ufsp(-/-) indicating the essential nature of this protease for Leishmania pathogenesis. Further, mouse infection experiments showed deletion of Ufsp results in reduced virulence of the parasites. Additionally, Ufsp activity was inhibited by an anti-leishmanial drug Amphotericin B. These studies provide an opportunity to test LdUfsp(-/-) parasites as drug and vaccine targets. Author Summary Ubiquitin and ubiquitin like proteins (Ubls) and the enzymes that mediate the conjugation/deconjugation reactions have not been well studied in protozoan parasites despite their widely recognized importance in a broad range of cellular functions in eukaryotes. We have previously reported that Ufm1 has distinct protein targets and cellular localization in the human parasite Leishmania donovani and deletion of Ufm1 in L. donovani adversely impacts the pathogenesis suggesting that Ufm1 associated enzymes could be exploited as drug targets. Using sensitive FRET based activity probes we identified the Ufm1 processing peptidase Ufsp in L. donovani. In addition, we show that deletion of Ufsp specifically reduces the survival of amastigotes, the parasite stage that is present in the humans thus altering the pathogenesis. Studies showing inhibition of Ufsp activity by anti-leishmanial drug further suggests that Leishmania Ufsp can serve as a novel target for pharmacological intervention for this parasite that causes deadly disease. C1 [Gannavaram, Sreenivas; Davey, Sonya; Lakhal-Naouar, Ines; Duncan, Robert; Nakhasi, Hira L.] US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Gannavaram, S (reprint author), US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM sreenivas.gannavaram@fda.hhs.gov; hira.nakhasi@fda.hhs.gov NR 37 TC 5 Z9 6 U1 0 U2 5 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 2014 VL 8 IS 2 AR e2707 DI 10.1371/journal.pntd.0002707 PG 12 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AB8CK UT WOS:000332017500008 PM 24587462 ER PT J AU Chamani, A Mehta, HP McDermott, MK Djeffal, M Nayyar, G Patwardhan, DV Attaluri, A Topoleski, LDT Zhu, L AF Chamani, Alireza Mehta, Hitesh P. McDermott, Martin K. Djeffal, Manel Nayyar, Gaurav Patwardhan, Dinesh V. Attaluri, Anilchandra Topoleski, L. D. Timmie Zhu, Liang TI Theoretical Simulation of Temperature Elevations in a Joint Wear Simulator During Rotations SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article DE bioheat transfer; joint simulator; temperature elevations; simulation ID CROSS-LINKED POLYETHYLENE; TOTAL HIP IMPLANTS; BEARING MATERIALS; HEAT-GENERATION; FINITE-ELEMENT; LUBRICANT; CUPS; REPLACEMENTS; ZIRCONIA; BEHAVIOR AB The objective of this study is to develop a theoretical model to simulate temperature fields in a joint simulator for various bearing conditions using finite element analyses. The frictional heat generation rate at the interface between a moving pin and a stationary base is modeled as a boundary heat source. Both the heat source and the pin are rotating on the base. We are able to conduct a theoretical study to show the feasibility of using the COMSOL software package to simulate heat transfer in a domain with moving components and a moving boundary source term. The finite element model for temperature changes agrees in general trends with experimental data. Heat conduction occurs primarily in the highly conductive base component, and high temperature elevation is confined to the vicinity of the interface in the pin. Thirty rotations of a polyethylene pin on a cobalt-chrome base for 60 s generate more than 2.26 degrees C in the temperature elevation from its initial temperature of 25 degrees C at the interface in a baseline model with a rotation frequency of 0.5 Hz. A higher heat generation rate is the direct result of a faster rotation frequency associated with intensity of exercise, and it results in doubling the temperature elevations when the frequency is increased by100%. Temperature elevations of more than 7.5 degrees C occur at the interface when the friction force is tripled from that in the baseline model. The theoretical modeling approach developed in this study can be used in the future to test different materials, different material compositions, and different heat generation rates at the interface under various body and environmental conditions. C1 [Chamani, Alireza; Topoleski, L. D. Timmie; Zhu, Liang] Univ Maryland Baltimore Cty, Dept Mech Engn, Baltimore, MD 21250 USA. [Mehta, Hitesh P.; McDermott, Martin K.; Djeffal, Manel; Nayyar, Gaurav; Patwardhan, Dinesh V.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Chem & Mat Sci, Silver Spring, MD 20993 USA. [Attaluri, Anilchandra] Johns Hopkins Univ, Baltimore, MD 21205 USA. RP Zhu, L (reprint author), Univ Maryland Baltimore Cty, Dept Mech Engn, Baltimore, MD 21250 USA. EM zliang@umbc.edu RI Mehta, Hitesh/I-1393-2013 FU University of Maryland Baltimore County FX This work was supported by the University of Maryland Baltimore County. NR 29 TC 0 Z9 0 U1 0 U2 9 PU ASME PI NEW YORK PA TWO PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 EI 1528-8951 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD FEB PY 2014 VL 136 IS 2 SI SI AR 021027 DI 10.1115/1.4026158 PG 6 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA AC4IE UT WOS:000332483700027 PM 24317017 ER PT J AU Borgert, CJ Stuchal, LD Mihaich, EM Becker, RA Bentley, KS Brausch, JM Coady, K Geter, DR Gordon, E Guiney, PD Hess, F Holmes, CM LeBaron, MJ Levine, S Marty, S Mukhi, S Neal, BH Ortego, LS Saltmiras, DA Snajdr, S Staveley, J Tobia, A AF Borgert, Christopher J. Stuchal, Leah D. Mihaich, Ellen M. Becker, Richard A. Bentley, Karin S. Brausch, John M. Coady, Katie Geter, David R. Gordon, Elliot Guiney, Patrick D. Hess, Frederick Holmes, Catherine M. LeBaron, Matthew J. Levine, Steve Marty, Sue Mukhi, Sandeep Neal, Barbara H. Ortego, Lisa S. Saltmiras, David A. Snajdr, Suzanne Staveley, Jane Tobia, Abraham TI Relevance Weighting of Tier 1 Endocrine Screening Endpoints by Rank Order SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Review DE endocrine disrupters; weight of evidence; endocrine screening; regulatory toxicology; Endocrine Disruptor Screening Program ID MINNOW PIMEPHALES-PROMELAS; RAT UTEROTROPHIC BIOASSAY; STEROID-BIOSYNTHESIS INHIBITORS; AMPHIBIAN METAMORPHOSIS ASSAY; THYROID-HORMONE ACTION; SPRAGUE-DAWLEY RATS; PLASMA SEX STEROIDS; MYKISS LIVER-CELLS; FATHEAD MINNOW; IN-VIVO AB Weight of evidence (WoE) approaches are recommended for interpreting various toxicological data, but few systematic and transparent procedures exist. A hypothesis-based WoE framework was recently published focusing on the U.S. EPA's Tier 1 Endocrine Screening Battery (ESB) as an example. The framework recommends weighting each experimental endpoint according to its relevance for deciding eight hypotheses addressed by the ESB. Here we present detailed rationale for weighting the ESB endpoints according to three rank ordered categories and an interpretive process for using the rankings to reach WoE determinations. Rank 1 was assigned to in vivo endpoints that characterize the fundamental physiological actions for androgen, estrogen, and thyroid activities. Rank 1 endpoints are specific and sensitive for the hypothesis, interpretable without ancillary data, and rarely confounded by artifacts or nonspecific activity. Rank 2 endpoints are specific and interpretable for the hypothesis but less informative than Rank 1, often due to oversensitivity, inclusion of narrowly context-dependent components of the hormonal system (e.g., in vitro endpoints), or confounding by nonspecific activity. Rank 3 endpoints are relevant for the hypothesis but only corroborative of Ranks 1 and 2 endpoints. Rank 3 includes many apical in vivo endpoints that can be affected by systemic toxicity and nonhormonal activity. Although these relevance weight rankings (W-REL) necessarily involve professional judgment, their a priori derivation enhances transparency and renders WoE determinations amenable to methodological scrutiny according to basic scientific premises, characteristics that cannot be assured by processes in which the rationale for decisions is provided post hoc. (C) 2014 Wiley Periodicals, Inc. C1 [Borgert, Christopher J.] Appl Pharmacol & Toxicol Inc, Gainesville, FL USA. [Stuchal, Leah D.] Univ Florida, Dept Physiol Sci, CEHT, Gainesville, FL 32610 USA. [Mihaich, Ellen M.] Environm & Regulatory Resources ER2, Durham, NC USA. [Becker, Richard A.] Amer Chem Council, Washington, DC USA. [Bentley, Karin S.; Snajdr, Suzanne] EI Pont Nemours, Wilmington, DE USA. [Brausch, John M.; Hess, Frederick; Holmes, Catherine M.] BASF Corp, Res Triangle Pk, NC USA. [Coady, Katie; LeBaron, Matthew J.; Marty, Sue] Dow Chem Co USA, Midland, MI 48674 USA. [Geter, David R.; Ortego, Lisa S.] Bayer CropSci LP, Res Triangle Pk, NC USA. [Gordon, Elliot] E Gordon Consulting LLC, Princeton Jct, NJ USA. [Guiney, Patrick D.] SC Johnson & Son Inc, Racine, WI USA. [Levine, Steve; Saltmiras, David A.] Monsanto Co, St Louis, MO USA. [Mukhi, Sandeep] FMC Agr Prod, Ewing, NJ USA. [Neal, Barbara H.] Exponent, Alexandria, VA USA. [Staveley, Jane] Exponent, Cary, NC USA. [Tobia, Abraham] US FDA, Silver Spring, MD USA. RP Borgert, CJ (reprint author), 2250 NW 24th Ave, Gainesville, FL 32605 USA. EM cjborgert@apt-pharmatox.com FU Endocrine Policy Forum FX Some substances under EPA EDSP Test Orders for endocrine screening are produced by the authors' employers. This article has been reviewed in accordance with the peer- and administrative-review policies of the authors' organizations. The views expressed here are those of the authors and do not necessarily reflect the opinions and/or policies of their employers. There are no contractual relations or proprietary considerations that restrict dissemination of the research findings of the authors. C.J. Borgert, E. M. Mihaich, and L. D. Stuchal are independent scientists/consultants who received financial support for portions of this project from the Endocrine Policy Forum. Time spent by other co-authors was supported by their respective employers or a personal contribution. NR 131 TC 9 Z9 9 U1 4 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-9733 EI 1542-9741 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD FEB PY 2014 VL 101 IS 1 SI SI BP 90 EP 113 DI 10.1002/bdrb.21096 PG 24 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA AA8TO UT WOS:000331368100008 PM 24510745 ER PT J AU Fox, WF Luna, L Schaur, G AF Fox, William F. Luna, LeAnn Schaur, Georg TI Destination taxation and evasion: Evidence from US inter-state commodity flows SO JOURNAL OF ACCOUNTING & ECONOMICS LA English DT Article DE Taxation; Evasion; Multijurisdictional ID TAX COMPETITION; BORDER AB Tax evasion has been an important issue in the accounting literature for several decades. but the focus has been on corporate income taxes. We develop a new way to examine tax evasion that focuses on corporate transactions, rather than corporate profits. Specifically, we examine how commodity flows respond to destination sales taxes, allowing for tax evasion as a function of distance between trade partners. After accounting for transportation costs, we find that the effect of taxes decreases as distance increases. This is consistent with the notion that longer distances between trade partners hinder government oversight and increase the likelihood of successful tax evasion. Our results are robust with respect to outliers, strategic neighbor effects, information sharing agreements and other re-specifications. These results are important to policymakers because they evidence the difficulty of enforcing destination taxation in open economies such as U.S. states and the European Union. (C) 2013 Elsevier B.V. All rights reserved. C1 [Fox, William F.] Univ Tennessee, Dept Econ, Knoxville, TN 37996 USA. [Fox, William F.; Luna, LeAnn] 715 Stokely Management Ctr, CBER, Knoxville, TN 37996 USA. [Luna, LeAnn] Univ Tennessee, Dept Accounting, Knoxville, TN 37996 USA. [Schaur, Georg] Univ Tennessee, Dept Econ, Stokely Management Center 505A, Knoxville, TN 37996 USA. RP Luna, L (reprint author), Univ Tennessee, Dept Accounting, Knoxville, TN 37996 USA. EM billfox@utk.edu; leann@utk.edu; gschaur@utk.edu NR 26 TC 4 Z9 4 U1 4 U2 30 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-4101 EI 1879-1980 J9 J ACCOUNT ECON JI J. Account. Econ. PD FEB PY 2014 VL 57 IS 1 BP 43 EP 57 DI 10.1016/j.jacceco.2013.12.001 PG 15 WC Business, Finance; Economics SC Business & Economics GA AC2QQ UT WOS:000332349400003 ER PT J AU Chagas, AC Oliveira, F Debrabant, A Valenzuela, JG Ribeiro, JMC Calvo, E AF Chagas, Andrezza C. Oliveira, Fabiano Debrabant, Alain Valenzuela, Jesus G. Ribeiro, Jose M. C. Calvo, Eric TI Lundep, a Sand Fly Salivary Endonuclease Increases Leishmania Parasite Survival in Neutrophils and Inhibits XIIa Contact Activation in Human Plasma SO PLOS PATHOGENS LA English DT Article ID LUTZOMYIA-LONGIPALPIS; EXTRACELLULAR TRAPS; INFECTION; FLIES; VECTOR; STREPTOCOCCUS; PROTECTION; MECHANISM; PROTEIN; GLANDS AB Neutrophils are the host's first line of defense against infections, and their extracellular traps (NET) were recently shown to kill Leishmania parasites. Here we report a NET-destroying molecule (Lundep) from the salivary glands of Lutzomyia longipalpis. Previous analysis of the sialotranscriptome of Lu. longipalpis showed the potential presence of an endonuclease. Indeed, not only was the cloned cDNA (Lundep) shown to encode a highly active ss- and dsDNAse, but also the same activity was demonstrated to be secreted by salivary glands of female Lu. longipalpis. Lundep hydrolyzes both ss- and dsDNA with little sequence specificity with a calculated DNase activity of 300000 Kunitz units per mg of protein. Disruption of PMA (phorbol 12 myristate 13 acetate)- or parasite-induced NETs by treatment with recombinant Lundep or salivary gland homogenates increases parasite survival in neutrophils. Furthermore, co-injection of recombinant Lundep with metacyclic promastigotes significantly exacerbates Leishmania infection in mice when compared with PBS alone or inactive (mutagenized) Lundep. We hypothesize that Lundep helps the parasite to establish an infection by allowing it to escape from the leishmanicidal activity of NETs early after inoculation. Lundep may also assist blood meal intake by lowering the local viscosity caused by the release of host DNA and as an anticoagulant by inhibiting the intrinsic pathway of coagulation. Author Summary Salivary components from disease vectors help the arthropod to acquire blood. Here we show that an arthropod vector salivary enzyme affects the innate immune system of the hostmainly the destruction of neutrophil trapsallowing the Leishmania parasite to evade the host immune response and to cause an infection. This work highlights the relevance of vector salivary components in parasite transmission and further suggests the inclusion of these proteins as components for an anti-Leishmania vaccine. Importantly, because salivary proteins are always present at the site of natural transmission, this work further encourages the testing of vaccine candidates using the natural route of transmissionthe bites of an arthropod vectorinstead of current practices based solely on needle injection of parasites. C1 [Chagas, Andrezza C.; Oliveira, Fabiano; Valenzuela, Jesus G.; Ribeiro, Jose M. C.; Calvo, Eric] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Debrabant, Alain] US FDA, Ctr Biol Evaluat & Res, Lab Emerging Pathogens, Bethesda, MD USA. RP Chagas, AC (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM ecalvo@niaid.nih.gov RI Oliveira, Fabiano/B-4251-2009; Ribeiro, Jose/J-7011-2015; OI Oliveira, Fabiano/0000-0002-7924-8038; Calvo, Eric/0000-0001-7880-2730; Ribeiro, Jose/0000-0002-9107-0818 FU Division of Intramural Research, NIAID, National Institutes of Health FX This work was funded by the Division of Intramural Research, NIAID, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 17 Z9 17 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD FEB PY 2014 VL 10 IS 2 AR e1003923 DI 10.1371/journal.ppat.1003923 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AB9CC UT WOS:000332085900031 PM 24516388 ER PT J AU Buxbaum, NP Farthing, DE Treadwell, S Bare, C Kapoor, V Telford, W Gress, R AF Buxbaum, Nataliya Prokopenko Farthing, Donald Eugene Treadwell, Shirin Bare, Catherine Kapoor, Veena Telford, William Gress, Ronald TI In Vivo T Regulatory Cell Kinetics Are Altered in a Pre-Clinical Model of Chronic Graft-Versus-Host Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT BMT Tandem Meetings CY FEB 26-MAR 02, 2014 CL Grapevine, TX C1 [Buxbaum, Nataliya Prokopenko; Farthing, Donald Eugene; Bare, Catherine; Kapoor, Veena; Telford, William] NCI, ETIB, NIH, Bethesda, MD 20892 USA. [Treadwell, Shirin] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Gress, Ronald] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. 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 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2014 VL 20 IS 2 SU 1 MA 45 BP S50 EP S51 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA AA5QT UT WOS:000331155400050 ER PT J AU Bowyer, JF Tranter, KM Sarkar, S Raymick, J Hanig, JP Schmued, LC AF Bowyer, John F. Tranter, Karen M. Sarkar, Sumit Raymick, James Hanig, Joseph P. Schmued, Larry C. TI Systemic Administration of Fluoro-Gold for the Histological Assessment of Vascular Structure, Integrity and Damage SO CURRENT NEUROVASCULAR RESEARCH LA English DT Article DE Fluoro-Gold; Blood-brain barrier; Vascular elements; Hemorrhage; Kainate; Amphetamine ID BLOOD-BRAIN-BARRIER; ALZHEIMERS-DISEASE; LONG-TERM; DIABETIC-RATS; METHAMPHETAMINE; TRACER; COMPLICATIONS; DEGENERATION; MICROVESSELS; HYPERTHERMIA AB Fluoro-Gold (F-G) has been used extensively as a fluorescent retrograde neuronal-track tracer in the past. We now report that intraperitoneal administration of 10 to 30 mg/kg of F-G from 30 min to 7 days prior to sacrifice labels vascular endothelial cells of the brain, choroid plexus and meninges and can be used to assess vascular integrity and damage. F-G vascular labeling co-localized with rat endothelial cell antigen (RECA-1) in the membrane. F-G also intensely labeled the nuclei of the endothelial cells, and co-localized with propidium iodide staining of these nuclei. As well, the administration of F-G during neurotoxic insults produced by amphetamine, kainic acid or "penetrating" wound to the brain can detect where vascular leakage/hemorrhage has occurred. Histological methods to detect F-G labeled brain vasculature were performed in the same manner as that used for fluorescent visualization of neuronal elements labeled with F-G after perfusion fixation and coronal sectioning (15 to 40 mu m) of the brain. This in vivo F-G labeling of endothelial cells and their nuclei yields a clear picture of the integrity of the vasculature and can be used to detect changes in structure. Vascular leaks after "penetrating" wounds through the cortex and striatum, hyperthermic amphetamine exposure or excitotoxic kainate exposure were detected by F-G in the extracellular space and via parenchymal F-G subsequently labeling the terminals and neurons adjacent to the lesioned or damaged vasculature. Further studies are necessary to determine the extent of the leakage necessary to detect vasculature damage. Visualization of the F-G labeling of vasculature structure and leakage is compatible with standard fluorescent immuno-labeling methods used to detect the presence and distribution of a protein in histological sections. This method should be directly applicable to studying brain vascular damage that occurs in the progression of Alzheimer's disease, diabetes and for monitoring the brain vascular changes during development. C1 [Bowyer, John F.; Sarkar, Sumit; Schmued, Larry C.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Tranter, Karen M.; Raymick, James] Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Hanig, Joseph P.] FDA Silver Spring, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Bowyer, JF (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT 132, Jefferson, AR 72079 USA. EM john.bowyer@fda.hhs.gov FU FDA [E7295, E7312, E7519] FX This study was supported by FDA protocol E7295, E# E7312 and E7519. NR 30 TC 3 Z9 3 U1 1 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2026 EI 1875-5739 J9 CURR NEUROVASC RES JI Curr. Neurovasc. Res. PD FEB PY 2014 VL 11 IS 1 BP 31 EP 47 DI 10.2174/1567202610666131124235011 PG 17 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AA8XI UT WOS:000331377900006 PM 24274907 ER PT J AU Sarkar, S Raymick, J Mann, D Bowyer, JF Hanig, JP Schmued, LC Paule, MG Chigurupati, S AF Sarkar, Sumit Raymick, James Mann, Dushyant Bowyer, John F. Hanig, Joseph P. Schmued, Larry C. Paule, Merle G. Chigurupati, Srinivasulu TI Neurovascular Changes in Acute, sub-Acute and Chronic Mouse Models of Parkinson's Disease SO CURRENT NEUROVASCULAR RESEARCH LA English DT Article DE Blood-brain barrier; Blood vessel; Endothelial cells; FT-gel; GFAP; MPTP; NeuN; Parkinson's disease; TH ID BLOOD-BRAIN-BARRIER; CORTICAL GLUCOSE-METABOLISM; VASCULAR BASEMENT-MEMBRANE; FLUORO-JADE-C; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; DOPAMINERGIC NEUROTOXICITY; NEUROTROPHIC FACTOR; ENDOTHELIAL-CELLS; HIGH-RESOLUTION AB Although selective neurodegeneration of nigro-striatal dopaminergic neurons is widely accepted as a cause of Parkinson's disease (PD), the role of vascular components in the brain in PD pathology is not well understood. However, the neurodegeneration seen in PD is known to be associated with neuroinflammatory-like changes that can affect or be associated with brain vascular function. Thus, dysfunction of the capillary endothelial cell component of neurovascular units present in the brain may contribute to the damage to dopaminergic neurons that occurs in PD. An animal model of PD employing acute, sub-acute and chronic exposures of mice to methyl-phenyl-tetrahydropyridine (MPTP) was used to determine the extent to which brain vasculature may be damaged in PD. Fluoro-Turquoise gelatin labeling of microvessels and endothelial cells was used to determine the extent of vascular damage produced by MPTP. In addition, tyrosine hydroxylase (TH) and NeuN were employed to detect and quantify dopaminergic neuron damage in the striatum (CPu) and substantia nigra (SNc). Gliosis was evaluated through GFAP immunohistochemistry. MPTP treatment drastically reduced TH immunoreactive neurons in the SNc (20.68+2.83 in acute; 22.98+2.14 in sub-acute; 10.20+2.24 in chronic vs 34.88+/-2.91in controls; p<0.001). Similarly, TH immunoreactive terminals were dramatically reduced in the CPu of MPTP treated mice. Additionally, all three MPTP exposures resulted in a decrease in the intensity, length, and number of vessels in both CPu and SNc. Degenerative vascular changes such as endothelial cell 'clusters' were also observed after MPTP suggesting that vasculature damage may be modifying the availability of nutrients and exposing blood cells and/or toxic substances to neurons and glia. In summary, vascular damage and degeneration could be an additional exacerbating factor in the progression of PD, and therapeutics that protect and insure vascular integrity may be novel treatments for PD. C1 [Sarkar, Sumit; Bowyer, John F.; Schmued, Larry C.; Paule, Merle G.; Chigurupati, Srinivasulu] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Mann, Dushyant] Wayne State Univ, Sch Med, Detroit, MI 48201 USA. [Hanig, Joseph P.] US FDA, CDER, Off Testing & Res, White Oak, MD 20993 USA. RP Sarkar, S (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Bldg 53D,HFT 32, Jefferson, AR 72079 USA. EM Sumit.Sarkar@FDA.hhs.gov FU National Center for Toxicological Research/FDA [E0751201] FX This study was supported by the National Center for Toxicological Research/FDA (E0751201). NR 80 TC 8 Z9 8 U1 0 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2026 EI 1875-5739 J9 CURR NEUROVASC RES JI Curr. Neurovasc. Res. PD FEB PY 2014 VL 11 IS 1 BP 48 EP 61 DI 10.2174/1567202610666131124234506 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AA8XI UT WOS:000331377900007 PM 24274908 ER PT J AU Laughon, MM Avant, D Tripathi, N Hornik, CP Cohen-Wolkowiez, M Clark, RH Smith, B Rodriguez, W AF Laughon, Matthew M. Avant, Debbie Tripathi, Nidhi Hornik, Christoph P. Cohen-Wolkowiez, Michael Clark, Reese H. Smith, Brian Rodriguez, William TI Drug Labeling and Exposure in Neonates SO JAMA PEDIATRICS LA English DT Article ID INHALED NITRIC-OXIDE; INTENSIVE-CARE-UNIT; VENTRICULAR TACHYARRHYTHMIA; GASTROESOPHAGEAL-REFLUX; RANDOMIZED MULTICENTER; PEDIATRIC POPULATION; PREGNANT-WOMEN; OFF-LABEL; INFANTS; PHARMACOKINETICS AB IMPORTANCE Federal legislation has led to a notable increase in pediatric studies submitted to the Food and Drug Administration (FDA), resulting in new pediatric information in product labeling. However, approximately 50% of drug labels still have insufficient information on safety, efficacy, or dosing in children. Neonatal information in labeling is even scarcer because neonates comprise a vulnerable subpopulation for which end-point development is lagging and studies are more challenging. OBJECTIVE To quantify progress made in neonatal studies and neonatal information in product labeling as a result of recent legislation. DESIGN, SETTING, AND PARTICIPANTS We identified a cohort of drug studies between 1997 and 2010 that included neonates as a result of pediatric legislation using information available on the FDA website. We determined what studies were published in the medical literature, the legislation responsible for the studies, and the resulting neonatal labeling changes. We then examined the use of these drugs in a cohort of neonates admitted to 290 neonatal intensive care units (NICUs) (the Pediatrix Data Warehouse) in the United States from 2005 to 2010. EXPOSURE Infants exposed to a drug studied in neonates as identified by the FDA website. MAIN OUTCOMES AND MEASURES Number of drug studies with neonates and rate of exposure per 1000 admissions among infants admitted to an NICU. RESULTS In a review of the FDA databases, we identified 28 drugs studied in neonates and 24 related labeling changes. Forty-one studies encompassed the 28 drugs, and 31 (76%) of these were published. Eleven (46%) of the 24 neonatal labeling changes established safety and effectiveness. In a review of a cohort of 446 335 hospitalized infants, we identified 399 drugs used and 1 525 739 drug exposures in the first 28 postnatal days. Thirteen (46%) of the 28 drugs studied in neonates were not used in NICUs; 8 (29%) were used in fewer than 60 neonates. Of the drugs studied, ranitidine was used most often (15 627 neonates, 35 exposures per 1000 admissions). CONCLUSIONS AND RELEVANCE Few drug labeling changes made under pediatric legislation include neonates. Most drugs studied are either not used or rarely used in US NICUs. Strategies to increase the study of safe and effective drugs for neonates are needed. C1 [Laughon, Matthew M.] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA. [Avant, Debbie; Rodriguez, William] Food & Drug Adm, Rockville, MD USA. [Tripathi, Nidhi; Hornik, Christoph P.; Cohen-Wolkowiez, Michael; Smith, Brian] Duke Clin Res Inst, Durham, NC USA. [Tripathi, Nidhi; Hornik, Christoph P.; Cohen-Wolkowiez, Michael; Smith, Brian] Duke Univ, Med Ctr, Durham, NC USA. [Clark, Reese H.] Pediatrix Ctr Res & Educ Sunrise, Sunrise, FL USA. RP Laughon, MM (reprint author), UNC Hosp, 101 Manning Dr,CB 7596,4th Floor, Chapel Hill, NC 27599 USA. EM matt_laughon@med.unc.edu RI Smith, Phillip/I-5565-2014 FU National Institutes of Health [5UL-1RR024128-01, 1K23HD064814]; US government [HHSN267200700051C]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [1K23HL092225-01]; Thrasher Research Fund; US Department of Health and Human Services (Eunice Kennedy Shriver National Institute of Child Health and Human Development) [1K23HD060040-01]; US Department of Health and Human Services (Department of Health and Human Services) [1R18AE000028-01]; US Department of Health and Human Services [HHSN267200700051C] FX This study used Clinical and Translational Science Award biostatistical services through the Division of Pediatric Quantitative Sciences (National Institutes of Health grant 5UL-1RR024128-01). Dr Laughon receives support from the US government for his work in pediatric and neonatal clinical pharmacology (government contract HHSN267200700051C, principal investigator D. K. Benjamin, Jr, MD, PhD, MPH, under the Best Pharmaceuticals for Children Act) and from Eunice Kennedy Shriver National Institute of Child Health and Human Development grant 1K23HL092225-01. Dr Cohen-Wolkowiez receives support for research from National Institutes of Health grant 1K23HD064814 and the nonprofit organization Thrasher Research Fund (www.thrasherresearch.org). Dr Smith receives salary support for research from the National Institutes of Health and the US Department of Health and Human Services (Eunice Kennedy Shriver National Institute of Child Health and Human Development grant 1K23HD060040-01, Department of Health and Human Services grant 1R18AE000028-01, and government contract HHSN267200700051C). NR 43 TC 33 Z9 33 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD FEB PY 2014 VL 168 IS 2 BP 130 EP 136 DI 10.1001/jamapediatrics.2013.4208 PG 7 WC Pediatrics SC Pediatrics GA AA8TD UT WOS:000331366900010 PM 24322269 ER PT J AU Samala, RK Chan, HP Lu, Y Hadjiiski, L Wei, J Sahiner, B Helvie, MA AF Samala, Ravi K. Chan, Heang-Ping Lu, Yao Hadjiiski, Lubomir Wei, Jun Sahiner, Berkman Helvie, Mark A. TI Computer-aided detection of clustered microcalcifications in multiscale bilateral filtering regularized reconstructed digital breast tomosynthesis volume SO MEDICAL PHYSICS LA English DT Article DE digital breast tomosynthesis; computer-aided detection; microcalcification; multiscale enhancement; regularized reconstruction ID INITIAL-EXPERIENCE; MAMMOGRAPHY; CLASSIFICATION; PERFORMANCE; OBSERVER; CALCIFICATIONS; POPULATION; VISIBILITY; PARAMETERS; PARADIGM AB Purpose: Develop a computer-aided detection (CADe) system for clustered microcalcifications in digital breast tomosynthesis (DBT) volume enhanced with multiscale bilateral filtering (MSBF) regularization. Methods: With Institutional Review Board approval and written informed consent, two-view DBT of 154 breasts, of which 116 had biopsy-proven microcalcification (MC) clusters and 38 were free of MCs, was imaged with a General Electric GEN2 prototype DBT system. The DBT volumes were reconstructed with MSBF-regularized simultaneous algebraic reconstruction technique (SART) that was designed to enhance MCs and reduce background noise while preserving the quality of other tissue structures. The contrast-to-noise ratio (CNR) of MCs was further improved with enhancement-modulated calcification response (EMCR) preprocessing, which combined multiscale Hessian response to enhance MCs by shape and bandpass filtering to remove the low-frequency structured background. MC candidates were then located in the EMCR volume using iterative thresholding and segmented by adaptive region growing. Two sets of potential MC objects, cluster centroid objects and MC seed objects, were generated and the CNR of each object was calculated. The number of candidates in each set was controlled based on the breast volume. Dynamic clustering around the centroid objects grouped the MC candidates to form clusters. Adaptive criteria were designed to reduce false positive (FP) clusters based on the size, CNR values and the number of MCs in the cluster, cluster shape, and cluster based maximum intensity projection. Free-response receiver operating characteristic (FROC) and jackknife alternative FROC (JAFROC) analyses were used to assess the performance and compare with that of a previous study. Results: Unpaired two-tailed t-test showed a significant increase (p < 0.0001) in the ratio of CNRs for MCs with and without MSBF regularization compared to similar ratios for FPs. For view-based detection, a sensitivity of 85% was achieved at an FP rate of 2.16 per DBT volume. For case-based detection, a sensitivity of 85% was achieved at an FP rate of 0.85 per DBT volume. JAFROC analysis showed a significant improvement in the performance of the current CADe system compared to that of our previous system (p = 0.003). Conclusions: MBSF regularized SART reconstruction enhances MCs. The enhancement in the signals, in combination with properly designed adaptive threshold criteria, effective MC feature analysis, and false positive reduction techniques, leads to a significant improvement in the detection of clustered MCs in DBT. (C) 2014 American Association of Physicists in Medicine. C1 [Samala, Ravi K.; Chan, Heang-Ping; Lu, Yao; Hadjiiski, Lubomir; Wei, Jun; Helvie, Mark A.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Sahiner, Berkman] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Samala, RK (reprint author), Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. EM rsamala@umich.edu OI Samala, Ravi/0000-0002-6661-4801 FU USPHS [RO1 CA151443]; University of Michigan investigators, through the Biomedical Research Partnership (USPHS) [CA91713] FX This work is supported by USPHS Grant No. RO1 CA151443. The digital breast tomosynthesis system was developed by the GE Global Research Group, with input and some revisions from the University of Michigan investigators, through the Biomedical Research Partnership (USPHS Grant No. CA91713, PI: Paul Carson, Ph.D.) collaboration. The content of this paper does not necessarily reflect the position of the funding agencies and no official endorsement of any equipment and product of any companies mentioned should be inferred. NR 31 TC 16 Z9 16 U1 2 U2 11 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 J9 MED PHYS JI Med. Phys. PD FEB PY 2014 VL 41 IS 2 AR 021901 DI 10.1118/1.4860955 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AA6MV UT WOS:000331213300034 PM 24506622 ER PT J AU Kim, IW Han, N Burckart, GJ Oh, JM AF Kim, In-Wha Han, Nayoung Burckart, Gilbert J. Oh, Jung Mi TI Epigenetic Changes in Gene Expression for Drug-Metabolizing Enzymes and Transporters SO PHARMACOTHERAPY LA English DT Article DE pharmacoepigenetics; personalized medicine; drug metabolism; DNA methylation; histone modification ID TUMOR-SPECIFIC EXPRESSION; ACUTE MYELOID-LEUKEMIA; HUMAN PROSTATE-CANCER; PREGNANE X RECEPTOR; DNA METHYLATION; PROMOTER REGION; MULTIDRUG-RESISTANCE; MESSENGER-RNA; INTERINDIVIDUAL DIFFERENCES; ABCG2 EXPRESSION AB Individual differences in drug response can be caused by genetic and epigenetic variability and disease determinants. Pharmacoepigenetics is a new field that studies the expression changes in pharmacogenes without changes in DNA sequences. Epigenetic control mechanisms are associated with DNA methylation, histone modification, small noncoding RNAs, and nucleosome remodeling. Researchers are actively attempting to identify epigenetic mechanisms for controlling the expression of enzymes and transporters affecting the metabolism and disposition of drugs. Current evidence suggests that epigenetic changes play a major role in cytochrome P450 enzyme expression, major transporter function, and in interactions with nuclear receptors. A thorough understanding of pharmacoepigenetics provides insight into new approaches to drug discovery and development, provides an understanding of previously observed actions of older drugs, and provides a pathway by which epigenetics can be harnessed to provide better patient-specific therapy. C1 [Kim, In-Wha; Han, Nayoung; Oh, Jung Mi] Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea. [Kim, In-Wha; Han, Nayoung; Oh, Jung Mi] Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul 151742, South Korea. [Burckart, Gilbert J.] US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Off Translat Sci, Silver Spring, MD USA. RP Oh, JM (reprint author), Seoul Natl Univ, Coll Pharm, 1 Gwanak Ro, Seoul 151742, South Korea. EM jmoh@snu.ac.kr FU National Research Foundation of Korea; Korean government Ministry of Science, ICT, and Future Planning [NRF-2009-00081414] FX inferred. This work was supported by the National Research Foundation of Korea grant, funded by the Korean government Ministry of Science, ICT, and Future Planning (no. NRF-2009-00081414). NR 79 TC 14 Z9 15 U1 0 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-0008 EI 1875-9114 J9 PHARMACOTHERAPY JI Pharmacotherapy PD FEB PY 2014 VL 34 IS 2 BP 140 EP 150 DI 10.1002/phar.1362 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AA6HH UT WOS:000331198900008 PM 24166985 ER PT J AU Mustonen, PSJ Oelbermann, M Kass, DCL AF Mustonen, P. S. Jorge Oelbermann, M. Kass, D. C. L. TI Response of the common bean (Phaseolus vulgaris L.) to Tithonia diversifolia (Hamsl.) Gray biomass retention or removal in a slash and mulch agroforestry system SO AGROFORESTRY SYSTEMS LA English DT Article DE Chirripo Rojo; Mycorrhiza; Negro Huasteco; Phosphorus; Root characteristics; Shoot characteristics ID SOIL CHEMICAL-PROPERTIES; PHOSPHORUS ACQUISITION; FALLOW SYSTEMS; GREEN MANURES; WESTERN KENYA; FERTILITY; MAIZE; PLANT; ROOT; CAPACITY AB The addition of mulch biomass from Tithonia diversifolia (Hemsl.) Gray prior to seeding may improve bean production. We evaluated the response of two Costa Rican bean cultivars (Chirripo Rojo, Negro Huasetco) to the retention or removal of T. diversifolia biomass with respect to soil chemical characteristics, and bean biomass, nutrient content, root architecture, and fungal structures. There were no significant differences (p < 0.05) between bean cultivars and their influence on soil characteristics. Soil pH, Ca and Mg were significantly lower (p < 0.05) at bean harvest in both biomass removal and retention treatments compared to those at the time of bean sowing, whereas exchangeable acidity was significantly greater (p < 0.05) at bean harvest. Bean shoot nutrient concentration differed significantly between cultivars but not between biomass retention or removal treatments except for Mg. Pod, leaf and stem biomass, root characteristics, and the number of root fungal structures (entry points, vesicles, arbuscules) were significantly different (p < 0.05) between bean cultivars and mulch biomass treatments. Results showed that T. diversifolia biomass positively influenced bean shoot and root characteristics, and suggested that the addition of mulch may have added relatively large quantities of P and K to the soil and stimulated the uptake of these nutrients. C1 [Mustonen, P. S. Jorge] Jorge & Mustonen SRL, Dept Agron, Santo Domingo, Dominican Rep. [Oelbermann, M.] Univ Waterloo, Dept Environm & Resource Studies, Waterloo, ON N2L 3G1, Canada. [Kass, D. C. L.] US FDA, Northeast Reg Lab, Jamaica, NY USA. RP Oelbermann, M (reprint author), Univ Waterloo, Dept Environm & Resource Studies, Waterloo, ON N2L 3G1, Canada. EM compay1_rd@hotmail.com; moelbermann@uwaterloo.ca; dclk9@hotmail.com OI Oelbermann, Maren/0000-0003-0996-4140 NR 37 TC 1 Z9 2 U1 2 U2 27 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-4366 EI 1572-9680 J9 AGROFOREST SYST JI Agrofor. Syst. PD FEB PY 2014 VL 88 IS 1 BP 1 EP 10 DI 10.1007/s10457-013-9650-9 PG 10 WC Agronomy; Forestry SC Agriculture; Forestry GA AA0FW UT WOS:000330772000001 ER PT J AU Major, JM Sargent, JD Graubard, BI Carlos, HA Hollenbeck, AR Altekruse, SF Freedman, ND McGlynn, KA AF Major, Jacqueline M. Sargent, James D. Graubard, Barry I. Carlos, Heather A. Hollenbeck, Albert R. Altekruse, Sean F. Freedman, Neal D. McGlynn, Katherine A. TI Local geographic variation in chronic liver disease and hepatocellular carcinoma: contributions of socioeconomic deprivation, alcohol retail outlets, and lifestyle SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Neighborhood; Socioeconomic disparities; Health care; Liver cancer; Liver disease; Cohort; Kernel density estimation; Multilevel; Census ID UNITED-STATES; RACIAL DISPARITY; SURVIVAL; ASSOCIATION; MORTALITY; HEALTH; RISK AB Purpose: Hepatocellular carcinoma (HCC) incidence rates continue to increase in the United States. Geographic variation in rates suggests a potential contribution of area-based factors, such as neighborhood socioeconomic deprivation, retail alcohol availability, and access to health care. Methods: Using the National Institutes of Health-American Association of Retired Persons Diet and Health Study, we prospectively examined area socioeconomic variations in HCC incidence (n = 434 cases) and chronic liver disease (CLD) mortality (n = 805 deaths) and assessed contribution of alcohol outlet density, health care infrastructure, diabetes, obesity, and health behaviors. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from hierarchical Cox regression models. Results: Area socioeconomic deprivation was associated with increased risk of HCC incidence and CLD mortality (HR, 1.48; 95% CI, 1.03-2.14 and HR, 2.36; 95% CI, 1.79-3.11, respectively) after accounting for age, sex, and race. After additionally accounting for educational attainment and health risk factors, associations for HCC incidence were no longer significant; associations for CLD mortality remained significant (HR, 1.78; 95% CI, 1.34-2.36). Socioeconomic status differences in alcohol outlet density and health behaviors explained the largest proportion of socioeconomic status-CLD mortality association, 10% and 29%, respectively. No associations with health care infrastructure were observed. Conclusions: Our results suggest a greater effect of area-based factors for CLD than HCC. Personal risk factors accounted for the largest proportion of variance for HCC but not for CLD mortality. Published by Elsevier Inc. C1 [Major, Jacqueline M.; Graubard, Barry I.; Freedman, Neal D.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Major, Jacqueline M.] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. [Sargent, James D.; Carlos, Heather A.] Dartmouth Coll, Norris Cotton Canc Ctr, Canc Control Res Program, Lebanon, NH 03756 USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. [Altekruse, Sean F.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Major, JM (reprint author), US FDA, Div Epidemiol, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM jacqueline.major@fda.hhs.gov RI Freedman, Neal/B-9741-2015 OI Freedman, Neal/0000-0003-0074-1098 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. Cancer incidence data from the Atlanta metropolitan area were collected by the Georgia Center for Cancer Statistics, Department of Epidemiology, Rollins School of Public Health, Emory University. Cancer incidence data from California were collected by the California Department of Health Services, Cancer Surveillance Section. Cancer incidence data from the Detroit metropolitan area were collected by the Michigan Cancer Surveillance Program, Community Health Administration, State of Michigan. The Florida cancer incidence data used in this report were collected by the Florida Cancer Data System under contract with the Florida Department of Health. The views expressed herein are solely those of the authors and do not necessarily reflect those of the Florida Cancer Data System or Florida Department of Health. Cancer incidence data from Louisiana were collected by the Louisiana Tumor Registry, Louisiana State University Medical Center in New Orleans. Cancer incidence data from New Jersey were collected by the New Jersey State Cancer Registry, Cancer Epidemiology Services, New Jersey State Department of Health and Senior Services. Cancer incidence data from North Carolina were collected by the North Carolina Central Cancer Registry. Cancer incidence data from Pennsylvania were supplied by the Division of Health Statistics and Research, Pennsylvania Department of Health, Harrisburg, Pennsylvania. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations, or conclusions. Cancer incidence data from Arizona were collected by the Arizona Cancer Registry, Division of Public Health Services, Arizona Department of Health Services. Cancer incidence data from Texas were collected by the Texas Cancer Registry, Cancer Epidemiology and Surveillance Branch, Texas Department of State Health Services. Cancer incidence data from Nevada were collected by the Nevada Central Cancer Registry, Center for Health Data and Research, Bureau of Health Planning and Statistics, State Health Division, State of Nevada Department of Health and Human Services. We are indebted to the participants in the NIH-AARP Diet and Health Study for their outstanding cooperation. The views expressed in this manuscript do not necessarily represent those of the Department of Health and Human Services or the U.S. Food and Drug Administration. NR 33 TC 8 Z9 8 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD FEB PY 2014 VL 24 IS 2 BP 104 EP 110 DI 10.1016/j.annepidem.2013.11.006 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA2GO UT WOS:000330913300004 PM 24332863 ER PT J AU Hong, HX Tong, WD AF Hong, Huixiao Tong, Weida TI Emerging efforts for discovering new biomarkers of liver disease and hepatotoxicity SO BIOMARKERS IN MEDICINE LA English DT Editorial Material DE biomarkers; discovery; hepatotoxicity; liver disease ID MICRORNAS; INJURY; CANCER C1 [Hong, Huixiao; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. RP Hong, HX (reprint author), US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM huixiao.hong@fda.hhs.gov; weida.tong@fda.hhs.gov NR 17 TC 7 Z9 7 U1 0 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 EI 1752-0371 J9 BIOMARK MED JI Biomark. Med. PD FEB PY 2014 VL 8 IS 2 BP 143 EP 146 DI 10.2217/bmm.13.156 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AA6MM UT WOS:000331212400001 PM 24521010 ER PT J AU Bhattacharyya, S Yan, K Pence, L Simpson, PM Gill, P Letzig, LG Beger, RD Sullivan, JE Kearns, GL Reed, MD Marshall, JD Van Den Anker, JN James, LP AF Bhattacharyya, Sudeepa Yan, Ke Pence, Lisa Simpson, Pippa M. Gill, Pritmohinder Letzig, Lynda G. Beger, Richard D. Sullivan, Janice E. Kearns, Gregory L. Reed, Michael D. Marshall, James D. Van Den Anker, John N. James, Laura P. TI Targeted liquid chromatography-mass spectrometry analysis of serum acylcarnitines in acetaminophen toxicity in children SO BIOMARKERS IN MEDICINE LA English DT Article DE -oxidation; acetaminophen; acylcarnitine; biomarker; clinical; hepatic; toxicity ID ACUTE LIVER-FAILURE; INDUCED HEPATIC-NECROSIS; PROTEIN ADDUCTS; INDUCED HEPATOTOXICITY; MICE; CLOFIBRATE; METABOLISM; OVERDOSE; METABOLOMICS; MULTICENTER AB Aim: Long-chain acylcarnitines have been postulated to be sensitive biomarkers of acetaminophen (APAP)-induced hepatotoxicity in mouse models. In the following study, the relationship of acylcarnitines with other known indicators of APAP toxicity was examined in children receiving low-dose (therapeutic) and high-dose (overdose' or toxic ingestion) exposure to APAP. Materials & methods: The study included three subject groups: group A (therapeutic dose, n = 187); group B (healthy controls, n = 23); and group C (overdose, n = 62). Demographic, clinical and laboratory data were collected for each subject. Serum samples were used for measurement of APAP protein adducts, a biomarker of the oxidative metabolism of APAP and for targeted metabolomics analysis of serum acylcarnitines using ultra performance liquid chromatography-triple-quadrupole mass spectrometry. Results: Significant increases in oleoyl- and palmitoyl-carnitines were observed with APAP exposure (low dose and overdose) compared with controls. Significant increases in serum ALT, APAP protein adducts and acylcarnitines were observed in overdose children that received delayed treatment (time to treatment from overdose >24 h) with the antidote N-acetylcysteine. Time to peak APAP protein adducts in serum was shorter than that of the acylcarnitines and serum ALT. Conclusion: Perturbations in long-chain acylcarnitines in children with APAP toxicity suggest that mitochrondrial injury and associated impairment in the -oxidation of fatty acids are clinically relevant as biomarkers of APAP toxicity. C1 [Bhattacharyya, Sudeepa; Gill, Pritmohinder; Letzig, Lynda G.; James, Laura P.] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72202 USA. [Bhattacharyya, Sudeepa; Gill, Pritmohinder; Letzig, Lynda G.; James, Laura P.] Arkansas Childrens Hosp, Res Inst, Little Rock, AR 72202 USA. [Yan, Ke; Simpson, Pippa M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Pence, Lisa; Beger, Richard D.] US FDA, Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA. [Sullivan, Janice E.] Univ Louisville, Kosair Char Pediat Clin Res Unit, Dept Pediat, Louisville, KY 40202 USA. [Sullivan, Janice E.] Univ Louisville, Kosair Char Pediat Clin Res Unit, Dept Pharmacol & Toxicol, Louisville, KY 40202 USA. [Sullivan, Janice E.] Kosair Childrens Hosp, Louisville, KY 40202 USA. [Kearns, Gregory L.] Childrens Mercy Hosp, Div Pediat Pharmacol Med Toxicol & Therapeut Inno, Kansas City, MO 64108 USA. [Reed, Michael D.] Northeast Ohio Med Univ, Dept Pediat, Div Clin Pharmacol & Toxicol, Akron, OH 44038 USA. [Reed, Michael D.] Akron Childrens Hosp, Rebecca D Considine Res Inst, Akron, OH 44308 USA. [Marshall, James D.] Childrens Hlth Care Syst, Ft Worth, TX 76104 USA. [Van Den Anker, John N.] Childrens Natl Med Ctr, Div Pediat Clin Pharmacol, Washington, DC 20010 USA. [James, Laura P.] Univ Arkansas Med Sci, Dept Pharmacol, Little Rock, AR 72205 USA. [James, Laura P.] Univ Arkansas Med Sci, Dept Toxicol, Little Rock, AR 72205 USA. RP James, LP (reprint author), Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72202 USA. EM jameslaurap@uams.edu FU National Institutes of Diabetes, Digestive and Kidney Diseases [R01 DK75936]; Arkansas Biosciences Institute; Arkansas Tobacco Settlement Funds FX This work was funded in part by a grant (R01 DK75936 to LP James) from the National Institutes of Diabetes, Digestive and Kidney Diseases and the Arkansas Biosciences Institute, which is funded by Arkansas Tobacco Settlement Funds. LP James is part owner of Acetaminophen Toxicity Diagnostics, LLC and has a patent pending for the development of a commercial assay for measurement of acetaminophen protein adducts. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 32 TC 13 Z9 13 U1 1 U2 18 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 EI 1752-0371 J9 BIOMARK MED JI Biomark. Med. PD FEB PY 2014 VL 8 IS 2 BP 147 EP 159 DI 10.2217/bmm.13.150 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AA6MM UT WOS:000331212400002 PM 24521011 ER PT J AU Wang, YP Chen, T Tong, WD AF Wang, Yuping Chen, Tao Tong, Weida TI miRNAs and their application in drug-induced liver injury SO BIOMARKERS IN MEDICINE LA English DT Review DE drug-induced liver injury; microRNA; translational biomarkers ID MAMMALIAN MICRORNA TARGETS; CIRCULATING MICRORNAS; HUMAN-DISEASE; GENE-EXPRESSION; KIDNEY-DISEASE; BREAST-CANCER; BODY-FLUIDS; BIOMARKERS; PLASMA; RNA AB The complex miRNA regulatory network plays an important role in diverse biological activities of physiopathological processes. In addition to the discovery of and research on the extracellular miRNAs detected in multiple biofluids, the properties of tissue specificity and high stability underlie the great potential of these small miRNAs to serve as translational biomarkers for various diseases in the clinical setting, including in drug-induced liver injury. In this review, we describe the major technologies currently used and challenges in miRNA measurement and provide information on major bioinformatics resources available for current miRNA research. We also discuss novel findings in liver disease and highlight the potential of miRNAs for clinical and basic research as translational biomarkers for drug-induced liver injury. C1 [Wang, Yuping; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. [Chen, Tao] US FDA, Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA. RP Tong, WD (reprint author), US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM weida.tong@fda.hhs.gov NR 102 TC 9 Z9 9 U1 0 U2 13 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 EI 1752-0371 J9 BIOMARK MED JI Biomark. Med. PD FEB PY 2014 VL 8 IS 2 BP 161 EP 172 DI 10.2217/bmm.13.147 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AA6MM UT WOS:000331212400003 PM 24521012 ER PT J AU Chen, MJ Bisgin, H Tong, L Hong, HX Fang, H Borlak, J Tong, WD AF Chen, Minjun Bisgin, Halil Tong, Lillian Hong, Huixiao Fang, Hong Borlak, Juergen Tong, Weida TI Toward predictive models for drug-induced liver injury in humans: are we there yet? SO BIOMARKERS IN MEDICINE LA English DT Article DE biomarker; drug label; drug safety; drug-induced liver injury; predictive model ID IN-SILICO MODELS; HUMAN HEPATOTOXICITY; HUMAN PHARMACOKINETICS; TOXICITY; ASSAY; QSAR; TOXICOGENOMICS; CLASSIFICATION; DISCOVERY; SAFETY AB Drug-induced liver injury (DILI) is a frequent cause for the termination of drug development programs and a leading reason of drug withdrawal from the marketplace. Unfortunately, the current preclinical testing strategies, including the regulatory-required animal toxicity studies or simple in vitro tests, are insufficiently powered to predict DILI in patients reliably. Notably, the limited predictive power of such testing strategies is mostly attributed to the complex nature of DILI, a poor understanding of its mechanism, a scarcity of human hepatotoxicity data and inadequate bioinformatics capabilities. With the advent of high-content screening assays, toxicogenomics and bioinformatics, multiple end points can be studied simultaneously to improve prediction of clinically relevant DILIs. This review focuses on the current state of efforts in developing predictive models from diverse data sources for potential use in detecting human hepatotoxicity, and also aims to provide perspectives on how to further improve DILI prediction. C1 [Chen, Minjun; Bisgin, Halil; Tong, Lillian; Hong, Huixiao; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. [Tong, Lillian] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA. [Fang, Hong] US FDA, Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA. [Borlak, Juergen] Hannover Med Sch, Ctr Pharmacol & Toxicol, Hannover, Germany. RP Tong, WD (reprint author), US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. EM weida.tong@fda.hhs.gov FU German Federal Ministry of Education and Research as part of the Virtual Liver Network initiative [031 6154]; ORISE of the US FDA FX J Borlak receives funding from the German Federal Ministry of Education and Research as part of the Virtual Liver Network initiative (grant number 031 6154). J Borlak is recipient of an ORISE stipend of the US FDA, which is gratefully acknowledged. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 92 TC 33 Z9 36 U1 4 U2 17 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 EI 1752-0371 J9 BIOMARK MED JI Biomark. Med. PD FEB PY 2014 VL 8 IS 2 BP 201 EP 213 DI 10.2217/bmm.13.146 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AA6MM UT WOS:000331212400006 PM 24521015 ER PT J AU Kugelman, JR Johnston, SC Mulembakani, PM Kisalu, N Lee, MS Koroleva, G McCarthy, SE Gestole, MC Wolfe, ND Fair, JN Schneider, BS Wright, LL Huggins, J Whitehouse, CA Wemakoy, EO Muyembe-Tamfum, JJ Hensley, LE Palacios, GF Rimoin, AW AF Kugelman, Jeffrey R. Johnston, Sara C. Mulembakani, Prime M. Kisalu, Neville Lee, Michael S. Koroleva, Galina McCarthy, Sarah E. Gestole, Marie C. Wolfe, Nathan D. Fair, Joseph N. Schneider, Bradley S. Wright, Linda L. Huggins, John Whitehouse, Chris A. Wemakoy, Emile Okitolonda Muyembe-Tamfum, Jean Jacques Hensley, Lisa E. Palacios, Gustavo F. Rimoin, Anne W. TI Genomic Variability of Monkeypox Virus among Humans, Democratic Republic of the Congo SO EMERGING INFECTIOUS DISEASES LA English DT Article ID ROCHE LIGHTCYCLER; SMALLPOX; INFECTION; TRANSMISSION; POXVIRUSES; SQUIRRELS; EVOLUTION; OUTBREAK; SEQUENCE; ECOLOGY AB Monkeypox virus is a zoonotic virus endemic to Central Africa. Although active disease surveillance has assessed monkeypox disease prevalence and geographic range, information about virus diversity is lacking. We therefore assessed genome diversity of viruses in 60 samples obtained from humans with primary and secondary cases of infection from 2005 through 2007. We detected 4 distinct lineages and a deletion that resulted in gene loss in 10 (16.7%) samples and that seemed to correlate with human-to-human transmission (p = 0.0544). The data suggest a high frequency of spillover events from the pool of viruses in nonhuman animals, active selection through genomic destabilization and gene loss, and increased disease transmissibility and severity. The potential for accelerated adaptation to humans should be monitored through improved surveillance. C1 [Kugelman, Jeffrey R.] US Army Med Res Inst Infect Dis, Ctr Genome Sci, Ft Detrick, MD USA. [Johnston, Sara C.; Lee, Michael S.; Koroleva, Galina; McCarthy, Sarah E.; Gestole, Marie C.; Huggins, John; Whitehouse, Chris A.; Palacios, Gustavo F.] US Army Med Res Inst Infect Dis, Ft Detrick, MD USA. [Mulembakani, Prime M.; Wemakoy, Emile Okitolonda] Kinshasa Sch Publ Hlth, Kinshasa, Zaire. [Kisalu, Neville; Rimoin, Anne W.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Wolfe, Nathan D.; Fair, Joseph N.; Schneider, Bradley S.] Global Viral Forecasting, San Francisco, CA USA. [Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Muyembe-Tamfum, Jean Jacques] Natl Inst Biomed Res, Kinshasa, Zaire. [Hensley, Lisa E.] US FDA, Silver Spring, MD USA. RP Rimoin, AW (reprint author), Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, 640 Charles E Young Dr S, Los Angeles, CA 90024 USA. EM gustavo.f.palacios.ctr@us.army.mil; arimoin@ucla.edu RI Palacios, Gustavo/I-7773-2015; OI Palacios, Gustavo/0000-0001-5062-1938; Schneider, Bradley S/0000-0001-7642-0018 FU Defense Threat Reduction Agency [1881290]; Metabiota; US Department of Defense Armed Forces Health Surveillance Center, Division of Global Emerging Infections, Surveillance Operations; Henry M. Jackson Foundation for the Advancement of Military Medicine; Defense Threat Reduction Agency Cooperative Biological Engagement Program; Google.org; Skoll Foundation; US Agency for International Development Emerging Pandemic Threats Program, PREDICT project [GHN-A-OO-09-00010-00] FX This work was funded by the Defense Threat Reduction Agency Project no. 1881290. The sample collection and epidemiologic study was partially financed by Metabiota, whose contribution was supported by the US Department of Defense Armed Forces Health Surveillance Center, Division of Global Emerging Infections, Surveillance Operations; the Henry M. Jackson Foundation for the Advancement of Military Medicine; the Defense Threat Reduction Agency Cooperative Biological Engagement Program; Google.org; the Skoll Foundation; and the US Agency for International Development Emerging Pandemic Threats Program, PREDICT project, under the terms of cooperative agreement no. GHN-A-OO-09-00010-00. NR 40 TC 9 Z9 9 U1 1 U2 10 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD FEB PY 2014 VL 20 IS 2 BP 232 EP 239 DI 10.3201/eid2002.130118 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 301TA UT WOS:000330553800008 PM 24457084 ER PT J AU Muindi, KM McCarthy, PC Wang, T Vionnet, J Battistel, M Jankowska, E Vann, WF AF Muindi, Karen M. McCarthy, Pumtiwitt C. Wang, Theresa Vionnet, Justine Battistel, Marcos Jankowska, Ewa Vann, Willie F. TI Characterization of the meningococcal serogroup X capsule N-acetylglucosamine-1-phosphotransferase SO GLYCOBIOLOGY LA English DT Article ID CONJUGATE VACCINE; MENINGITIDIS; POLYSIALYLTRANSFERASE; PURIFICATION; TRANSFERASE; ANTIGENS; SUBUNIT; DISEASE; MOTIFS AB Neisseria meningitidis serogroups A, B, C, Y, W135 and X are responsible for most cases of meningococcal meningitis. Neisseria meningitidis serogroup X has recently emerged as a contributor to outbreaks of disease in Africa, but there is currently no vaccine against serogroup X. Understanding of the biosynthesis of the serogroup X capsular polysaccharide would provide useful tools for vaccine production. The serogroup X polysaccharide is a homopolymer of (alpha 1 -> 4)-linked N-acetylglucosamine (GlcNAc)-1-phosphate. It has been shown that the gene cluster xcbABC encodes synthesis of this polysaccharide. The xcbA gene product has significant homology with sacB, which is responsible for synthesis of the Neisseria serogroup A capsular polysaccharide, an (alpha 1 -> 6)-N-acetylmannosamine-1-phosphate homopolymer. The xcbA protein also shares homology with the catalytic domain of human N-acetylglucosamine-1-phosphoryltransferase, a key enzyme in the mannose-6-phosphate receptor pathway. In this study, we show that xcbA in the appropriate background is sufficient for the synthesis of N. meningitidis serogroup X polysaccharide. By ELISA we detected polysaccharide in fractions of Escherichia coli expressing the xcbA gene. We isolated polysaccharide from an E. coli strain expressing XcbA and demonstrated that this polysaccharide has a C-13-NMR spectrum identical to that of polysaccharide isolated from N. meningitidis Group X. We also demonstrate that the purified XcbA protein is an N-acetylglucosamine-1-phosphotransferase that transfers N-acetylglucosamine-1-phosphate from UDP-GlcNAc to the 4-hydroxyl of an N-acetylglucosamine-1-phosphate oligosaccharide. Oligosaccharides fluorescently labeled at the aglycon are extended by XcbA only after the 4-phosphate occupying the non-reducing GlcNAc has been removed. The minimum size of fluorescent acceptors is a trisaccharide. C1 [Muindi, Karen M.; McCarthy, Pumtiwitt C.; Wang, Theresa; Vionnet, Justine; Battistel, Marcos; Jankowska, Ewa; Vann, Willie F.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Vann, WF (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM willie.vann@fda.hhs.gov FU CRADA FX This work was partially supported by a CRADA between the Food and Drug Administration and the Program for Appropriate Technology in Health-PATH. NR 28 TC 4 Z9 4 U1 2 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 EI 1460-2423 J9 GLYCOBIOLOGY JI Glycobiology PD FEB PY 2014 VL 24 IS 2 BP 139 EP 149 DI 10.1093/glycob/cwt091 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA1EM UT WOS:000330839300003 PM 24134880 ER PT J AU Harris, M Bhuvaneshwar, K Natarajan, T Sheahan, L Wang, DF Tadesse, MG Shoulson, I Filice, R Steadman, K Pishvaian, MJ Madhavan, S Deeken, J AF Harris, Michael Bhuvaneshwar, Krithika Natarajan, Thanemozhi Sheahan, Laura Wang, Difei Tadesse, Mahlet G. Shoulson, Ira Filice, Ross Steadman, Kenneth Pishvaian, Michael J. Madhavan, Subha Deeken, John TI Pharmacogenomic characterization of gemcitabine response - a framework for data integration to enable personalized medicine SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE DMET; gemcitabine; NCI-60; pancreatic cancer; probabilistic networks ID SINGLE-NUCLEOTIDE POLYMORPHISMS; GENOME-WIDE ASSOCIATION; PREGNANE-X RECEPTOR; PANCREATIC-CANCER; BAYESIAN NETWORKS; GENE-EXPRESSION; FUNCTIONAL-ANALYSIS; CYTIDINE DEAMINASE; HUMAN HEPATOCYTES; TARGET GENES AB ObjectivesResponse to the oncology drug gemcitabine may be variable in part due to genetic differences in the enzymes and transporters responsible for its metabolism and disposition. The aim of our in-silico study was to identify gene variants significantly associated with gemcitabine response that may help to personalize treatment in the clinic.MethodsWe analyzed two independent data sets: (a) genotype data from NCI-60 cell lines using the Affymetrix DMET 1.0 platform combined with gemcitabine cytotoxicity data in those cell lines, and (b) genome-wide association studies (GWAS) data from 351 pancreatic cancer patients treated on an NCI-sponsored phase III clinical trial. We also performed a subset analysis on the GWAS data set for 135 patients who were given gemcitabine+placebo. Statistical and systems biology analyses were performed on each individual data set to identify biomarkers significantly associated with gemcitabine response.ResultsGenetic variants in the ABC transporters (ABCC1, ABCC4) and the CYP4 family members CYP4F8 and CYP4F12, CHST3, and PPARD were found to be significant in both the NCI-60 and GWAS data sets. We report significant association between drug response and variants within members of the chondroitin sulfotransferase family (CHST) whose role in gemcitabine response is yet to be delineated.ConclusionBiomarkers identified in this integrative analysis may contribute insights into gemcitabine response variability. As genotype data become more readily available, similar studies can be conducted to gain insights into drug response mechanisms and to facilitate clinical trial design and regulatory reviews. (C) 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Harris, Michael; Bhuvaneshwar, Krithika; Natarajan, Thanemozhi; Sheahan, Laura; Wang, Difei; Madhavan, Subha] Georgetown Univ, Med Ctr, Innovat Ctr Biomed Informat, Washington, DC 20007 USA. [Harris, Michael; Steadman, Kenneth; Pishvaian, Michael J.; Madhavan, Subha; Deeken, John] Georgetown Univ, Med Ctr, Dev Therapeut Program, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Shoulson, Ira] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20007 USA. [Tadesse, Mahlet G.] Georgetown Univ, Dept Math & Stat, Washington, DC 20007 USA. [Sheahan, Laura] ESAC Inc, Rockville, MD USA. [Filice, Ross] US FDA, Silver Spring, MD USA. RP Madhavan, S (reprint author), Georgetown Univ, Med Ctr, Innovat Ctr Biomed Informat, 2115 Wisconsin Ave NW,Suite 110, Washington, DC 20007 USA. EM sm696@georgetown.edu RI Wang, Difei/E-7066-2010 FU FDA Centers of Excellence in Regulatory Science and Innovation (CER-SI) [FDA U01 FD004319]; National Cancer Institute [P30CA051008] FX This work was supported, in part, by the FDA Centers of Excellence in Regulatory Science and Innovation (CER-SI) (FDA U01 FD004319), and by the National Cancer Institute (P30CA051008). The content is solely the responsibility of the authors and does not necessarily represent the official views of the FDA, the National Cancer Institute, or the National Institutes of Health. Support for research computing resources was provided by the Amazon Corporation. NR 77 TC 4 Z9 6 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1744-6872 EI 1744-6880 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD FEB PY 2014 VL 24 IS 2 BP 81 EP 93 DI 10.1097/FPC.0000000000000015 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA AA1TT UT WOS:000330879300001 PM 24401833 ER PT J AU Chen, S Xuan, JK Wan, LQ Lin, HX Couch, L Mei, N Dobrovolsky, VN Guo, L AF Chen, Si Xuan, Jiekun Wan, Liqing Lin, Haixia Couch, Letha Mei, Nan Dobrovolsky, Vasily N. Guo, Lei TI Sertraline, an Antidepressant, Induces Apoptosis in Hepatic Cells Through the Mitogen-Activated Protein Kinase Pathway SO TOXICOLOGICAL SCIENCES LA English DT Article DE sertraline; liver toxicity; mitochondrial dysfunction; apoptosis; cell death; MAPK pathway ID SEROTONIN REUPTAKE INHIBITORS; GENE-EXPRESSION CHANGES; LIVER HEPG2 CELLS; OF-THE-LITERATURE; C-JUN; MAP KINASE; MITOCHONDRIAL DYSFUNCTION; TRICYCLIC ANTIDEPRESSANTS; INDUCED CYTOTOXICITY; CASPASE-3 PATHWAYS AB Sertraline is generally used for the treatment of depression and is also approved for the treatment of panic, obsessive-compulsive, and posttraumatic stress disorders. Previously, using rat primary hepatocytes and isolated mitochondria, we demonstrated that sertraline caused hepatic cytotoxicity and mitochondrial impairment. In the current study, we investigated and characterized molecular mechanisms of sertraline toxicity in human hepatoma HepG2 cells. Sertraline decreased cell viability and induced apoptosis in a dose- and time-dependent manner. Sertraline activated the intrinsic checkpoint protein caspase-9 and caused the release of cytochrome c from mitochondria to cytosol; this process was Bcl-2 family dependent because antiapoptotic Bcl-2 family proteins were decreased. Pretreatment of the HepG2 cells with caspase-3, caspase-8, and caspase-9 inhibitors partially but significantly reduced the release of lactate dehydrogenase, indicating that sertraline-induced apoptosis is mediated by both intrinsic and extrinsic apoptotic pathways. Moreover, sertraline markedly increased the expression of tumor necrosis factor (TNF) and the phosphorylation of JNK, extracellular signal-regulated kinase (ERK1/2), and p38. In sertraline-treated cells, the induction of apoptosis and cell death was shown to be the result of activation of JNK, but not ERK1/2 or p38 in the mitogen-activated protein kinase (MAPK) pathway. Furthermore, silencing MAP4K4, the upstream kinase of JNK, attenuated both apoptosis and cell death caused by sertraline. Taken together, our findings suggest that sertraline induced apoptosis in HepG2 cells at least partially via activation of the TNF-MAP4K4-JNK cascade signaling pathway. C1 [Chen, Si; Xuan, Jiekun; Wan, Liqing; Couch, Letha; Guo, Lei] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Wan, Liqing] Shanghai Inst Food & Drug Control, Shanghai 201203, Peoples R China. [Lin, Haixia; Mei, Nan; Dobrovolsky, Vasily N.] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Guo, L (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT-110, Jefferson, AR 72079 USA. EM lei.guo@fda.hhs.gov RI mei, nan/E-8915-2011; Lin, Haixia /J-4772-2015 OI mei, nan/0000-0002-3501-9014; FU U.S. FDA's International Scientist Exchange Program FX S.C., J.X., and H.L. were supported by appointments to the Postgraduate Research Program at the National Center for Toxicological Research administered by the Oak Ridge Institute for Science Education through an interagency agreement between the U.S. Department of Energy and the U.S. FDA. L.W. was supported by the U.S. FDA's International Scientist Exchange Program. NR 62 TC 14 Z9 14 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 2014 VL 137 IS 2 BP 404 EP 415 DI 10.1093/toxsci/kft254 PG 12 WC Toxicology SC Toxicology GA AA2RU UT WOS:000330942600011 PM 24194395 ER PT J AU Menis, M Anderson, SA Forshee, RA McKean, S Johnson, C Holness, L Warnock, R Gondalia, R Worrall, CM Kelman, JA Ball, R Izurieta, HS AF Menis, M. Anderson, S. A. Forshee, R. A. McKean, S. Johnson, C. Holness, L. Warnock, R. Gondalia, R. Worrall, C. M. Kelman, J. A. Ball, R. Izurieta, H. S. TI Transfusion-associated circulatory overload (TACO) and potential risk factors among the inpatient US elderly as recorded in Medicare administrative databases during 2011 SO VOX SANGUINIS LA English DT Article DE Transfusion-Associated Circulatory Overload; risk factors; inpatient elderly; Medicare administrative databases ID ACUTE LUNG INJURY; PULMONARY-EDEMA AB Background and Objectives Transfusion-associated circulatory overload (TACO) is a serious transfusion complication resulting in respiratory distress. The study's objective was to assess TACO occurrence and potential risk factors among elderly Medicare beneficiaries (ages 65 and older) in the inpatient setting during 2011. Materials and Methods This retrospective claims-based study utilized Medicare administrative databases in coordination with Centers for Medicare & Medicaid Services. Transfusions were identified by recorded procedure and revenue centre codes, while TACO was ascertained via ICD-9-CM diagnosis code. We evaluated TACO diagnosis code rates overall and by age, gender, race, number of units and blood components transfused. Multivariate logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results Among 2147038 inpatient transfusion stays for elderly in 2011, 1340 had TACO diagnosis code, overall rate of 624 per 100000 stays. TACO rates increased significantly with age and units transfused (P<00001). After adjustment for confounding, significantly higher odds of TACO were found for women vs. men (OR=140, 95% CI 126-160), White people vs. non-White people (OR=138, 95% CI 120-162) and persons with congestive heart failure (OR=161, 95% CI 144-188), chronic pulmonary disease (OR=119, 95% CI 108-132) and different anaemias. Conclusion Our study identified largest number of potential TACO cases to date and showed a substantial increase in TACO occurrence with age and number of units transfused. The study suggested increased TACO risk in elderly with congestive heart failure, chronic pulmonary disease and anaemias. Overall, study shows importance of large administrative databases as an additional epidemiological tool. C1 [Menis, M.; Anderson, S. A.; Forshee, R. A.; Holness, L.; Ball, R.; Izurieta, H. S.] US FDA, Rockville, MD 20852 USA. [McKean, S.; Johnson, C.; Warnock, R.; Gondalia, R.] Acumen LLC, Burlingame, CA USA. [Worrall, C. M.; Kelman, J. A.] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. RP Menis, M (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 225, Rockville, MD 20852 USA. EM mikhail.menis@fda.hhs.gov FU US Food and Drug Administration, Center for Biologics Evaluation and Research FX This study was funded by the US Food and Drug Administration, Center for Biologics Evaluation and Research. We thank Garner Kropp and Emily Wang for their contribution during the initial stages of study analyses. All authors made substantial contributions to research design, or the acquisition, analysis or interpretation of data and were involved in drafting of the paper or revising it critically. The manuscript has been approved by all authors. NR 27 TC 13 Z9 13 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0042-9007 EI 1423-0410 J9 VOX SANG JI Vox Sang. PD FEB PY 2014 VL 106 IS 2 BP 144 EP 152 DI 10.1111/vox.12070 PG 9 WC Hematology SC Hematology GA AA4SL UT WOS:000331086300007 PM 23848234 ER PT J AU Clarke, IC Lazennec, JY Brusson, A Savisaar, C Bowsher, JG Burgett, M Donaldson, TK AF Clarke, Ian C. Lazennec, Jean-Yves Brusson, Adrien Savisaar, Christina Bowsher, John G. Burgett, Michelle Donaldson, Thomas K. TI Risk of Impingement and Third-body Abrasion With 28-mm Metal-on-metal Bearings SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Open Scientific Meeting of the Hip-Society in Conjunction with the Annual Meeting of the American-Academy-of-Orthopaedic-Surgeons (AAOS) CY 2013 CL Chicago, IL SP Hip Soc, Amer Acad Orthopaed Surg ID TOTAL HIP-REPLACEMENT; CERAMIC FEMORAL HEADS; LONG-TERM WEAR; ACETABULAR COMPONENT; ARTICULAR SURFACE; LINER IMPINGEMENT; EARLY OSTEOLYSIS; EARLY FAILURE; ION LEVELS; ALUMINA AB Concerns have been raised about the sequelae of metal-on-metal (MoM) bearings in total hip arthroplasty (THA). However, retrieval studies, which offer the best insight into the clinically relevant mechanisms of MoM wear, have followed predictable trends to date such as indicting cobalt-chromium (CoCr) metallurgy, cup design, high conformity between the head and cup, "steep cups," "microseparation," and "edge wear." We wished to evaluate a set of retrieved 28-mm MoM THA for signs of (1) cup-to-stem impingement; (2) normal wear pattern and concomitant stripe damage on femoral heads that would signify adverse wear mechanics; and (3) well-defined evidence of third-body scratches on bearings that would indicate large abrasive particles had circulated the joint space. Ten 28-mm MOM retrievals were selected on the basis that femoral stems were included. Revision surgeries at 3 to 8 years were for pain, osteolysis, and cup loosening. CoCr stems and the MoM bearings were produced by one vendor and Ti6Al4V stems by a second vendor. All but two cases had been fixed with bone cement. We looked for patterns of normal wear and impingement signs on femoral necks and cup rims. We looked for adverse wear defined as stripe damage that was visually apparent on each bearing. Wear patterns were examined microscopically to determine the nature of abrasions and signs of metal transfer. Graphical models recreated femoral neck and cup designs to precisely correlate impingement sites on femoral necks to cup positions and head stripe patterns. The evidence revealed that all CoCr cup liners had impinged on either anterior or posterior facets of femoral necks. Liner impingement at the most proximal neck notch occurred with the head well located and impingement at the distal notch occurred with the head rotated 5 mm out of the cup. The hip gained 20A degrees motion by such a subluxation maneuver with this THA design. All heads had stripe wear, the basal and polar stripes coinciding with cup impingement sites. Analysis of stripe damage revealed 40 to 100-mu m wide scratches created by large particles ploughing across bearing surfaces. The association of stripe wear with evidence of neck notching implicated impingement as the root cause, the outcome being the aggressive third-body wear. We found consistent evidence of impingement, abnormal stripe damage, and evidence of third-body abrasive wear in a small sample of one type of 28-mm MoM design. Impingement models demonstrated that 28-mm heads could lever 20A degrees out of the liners. Although other studies continue to show good success with 28-mm MoM bearings, their use has been discontinued at La Pitie Hospital. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. C1 [Clarke, Ian C.] Loma Linda Univ, Dept Orthopaed, Loma Linda, CA 92350 USA. [Clarke, Ian C.; Burgett, Michelle] DARF Ctr, Colton, CA 92324 USA. [Lazennec, Jean-Yves; Brusson, Adrien] UPMC Univ, Dept Orthopaed, La Pitie Hosp, Paris, France. [Savisaar, Christina; Bowsher, John G.] US FDA, Silver Spring, MD USA. [Donaldson, Thomas K.] Empire Orthoped, Colton, CA USA. RP Clarke, IC (reprint author), DARF Ctr, 900E Washington St 200, Colton, CA 92324 USA. EM hipgeek5@yahoo.com NR 80 TC 5 Z9 5 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD FEB PY 2014 VL 472 IS 2 BP 497 EP 508 DI 10.1007/s11999-013-3399-3 PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 302EP UT WOS:000330585000017 PM 24297107 ER PT J AU Thompson, KE Zeng, K Wilson, CM Gaber, MW Miller, DD Yates, CR AF Thompson, Karin E. Zeng, Kui Wilson, Christy M. Gaber, Mostafa W. Miller, Duane D. Yates, Charles R. TI Quinic Acid Derivative KZ-41 Exhibits Radiomitigating Activity in Preclinical Models of Radiation Injury SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE total body irradiation; wound healing; radiomitigant; vascular injury; radiation combined injury ID UNCARIA-TOMENTOSA; AQUEOUS EXTRACT; REPERFUSION; MANAGEMENT; AGENTS AB Acute radiation syndrome is induced when a significant portion of the body receives highdose, as well as highdose rate, radiation. We have previously identified a quinic acidbased derivative, KZ-41, that protects from radiation injury. Further preclinical efficacy studies were conducted to determine the radiomitigating activity of KZ-41. C57BL/6 mice received total body irradiation (TBI-LD80/30, Cs-137; a?1/42min) followed by either normal saline or KZ-41 (100mg/kg sc a?1/426h postTBI). KZ-41 increased 30day survival by approximately 45% compared with vehicle controls (P<0.05). To further investigate the potential radiomodulating mechanisms of KZ-41, we developed a combined radiation and vascular injury model. C57BL/6 mice surgically fixed with dorsal windows for dermal vasculature imaging received either sham or TBI (Cs-137; 6 Gray). Postcapillary venule injury was induced (24, 48, 72, and 96h postTBI) followed by imaging at 5min and 24h to assess clot formation and blood flow. Impairment in flow (P<0.05) and clot formation (P<0.05) were observed as early as 48 and 72h, respectively. Thus, vascular injury 72h postTBI was used to evaluate intervention (KZ-41; 100mg/kg i.p. at 12, 36, and 60h postTBI) on radiationinduced changes in both flow and clot formation. KZ-41, although not improving flow, increased clot formation (P<0.05). Platelet counts were lower in both irradiated groups compared with sham controls (P<0.05). In summary, KZ-41 exerts radiomitigating activity in lethally irradiated mice. Imaging results suggest KZ-41 exerts radiomitigating activity through mechanisms involving promotion of initial clot formation and vascular flow restoration. The imaging model described herein is useful for further examination of radiationinduced vascular injury repair mechanisms. (C) 2013 Wiley Periodicals, Inc.(C)2013 Wiley Periodicals, Inc. C1 [Thompson, Karin E.; Miller, Duane D.; Yates, Charles R.] Univ Tennessee, Ctr Hlth Sci, Dept Pharmaceut Sci, Memphis, TN 38163 USA. [Zeng, Kui] US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. [Wilson, Christy M.] Duke Univ, Durham, NC 27708 USA. [Gaber, Mostafa W.] Baylor Coll Med, Houston, TX 77030 USA. RP Yates, CR (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Pharmaceut Sci, 881 Madison Ave,Pharm Bldg Room 446, Memphis, TN 38163 USA. EM cyates4@uthsc.edu FU National Institute of Allergy and Infectious Disease [5R21AI080534]; University of Tennessee College of Pharmacy; RxBio Inc.; ED Labs, Inc. FX This research was supported by National Institute of Allergy and Infectious Disease grant number 5R21AI080534, The University of Tennessee College of Pharmacy, RxBio Inc., and ED Labs, Inc. This technology is patent pending and is owned by The University of Tennessee Research Foundation. NR 22 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0272-4391 EI 1098-2299 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD FEB PY 2014 VL 75 IS 1 SI SI BP 29 EP 36 DI 10.1002/ddr.21164 PG 8 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AA0ND UT WOS:000330791000005 PM 24648047 ER PT J AU Liu, P Zafar, F Badano, A AF Liu, Peter Zafar, Fahad Badano, Aldo TI The Effect of Ambient Illumination on Handheld Display Image Quality SO JOURNAL OF DIGITAL IMAGING LA English DT Article DE Clinical image viewing; Data display; Diagnostic display monitors; Diagnostic image quality; Digital display; Display device; Human-computer interaction; Human visual system; Image display; Liquid crystal display (LCD); Medical displays; Personal digital assistant (PDA); Visual perception ID MOBILE DISPLAY AB Handheld devices such as smartphones and tablets are becoming useful in the medical field, as they allow physicians, radiologists, and researchers to analyze images with the benefit of mobile accessibility. However, for handheld devices to be effective, the display must be able to perform well in a wide range of ambient illumination conditions. We conducted visual experiments to quantify user performance for testing the image quality of two current-generation devices in different ambient illumination conditions while measuring ambient light levels with a real-time illuminance meter. We found and quantified that due to the high reflectivity of handheld devices, performance deteriorates as the user moves from dark areas into environments of greater ambient illumination. The quantitative analysis suggests that differences in display reflection coefficients do not affect the low illumination performance of the device but rather the performance at higher levels of illumination. C1 [Badano, Aldo] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol, Silver Spring, MD 20993 USA. [Liu, Peter] Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA. [Zafar, Fahad] Univ Maryland Baltimore Cty, Dept Elect & Comp Engn, Baltimore, MD 21228 USA. RP Badano, A (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM aldo.badano@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 FU Research Participation Program FX The authors acknowledge support from the Research Participation Program administered by ORISE through an interagency agreement between DOE and FDA. The mention of commercial products herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services. This is a contribution of the Food and Drug Administration and is not subject to copyright. We thank the volunteers who participated in the experiments. NR 9 TC 5 Z9 6 U1 0 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0897-1889 EI 1618-727X J9 J DIGIT IMAGING JI J. Digit. Imaging PD FEB PY 2014 VL 27 IS 1 BP 12 EP 18 DI 10.1007/s10278-013-9636-1 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 304FY UT WOS:000330733700003 PM 24113844 ER PT J AU Murbach, M Neufeld, E Kainz, W Pruessmann, KP Kuster, N AF Murbach, Manuel Neufeld, Esra Kainz, Wolfgang Pruessmann, Klaas P. Kuster, Niels TI Whole-Body and Local RF Absorption in Human Models as a Function of Anatomy and Position within 1.5T MR Body Coil SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE local field enhancement; specific absorption rate; large-scale anatomical property; safety ID CHILDREN AB PurposeRadiofrequency energy deposition in magnetic resonance imaging must be limited to prevent excessive heating of the patient. Correlations of radiofrequency absorption with large-scale anatomical features (e.g., height) are investigated in this article. Theory and MethodsThe specific absorption rate (SAR), as the pivotal parameter for quantifying absorbed radiofrequency, increases with the radial dimension of the patient and therefore with the large-scale anatomical properties. The absorbed energy in six human models has been modeled in different Z-positions (head to knees) within a 1.5T bodycoil. ResultsFor a fixed B1+ incident field, the whole-body SAR can be up to 2.5 times higher (local SAR up to seven times) in obese adult models compared to children. If the exposure is normalized to 4 W/kg whole-body SAR, the local SAR can well-exceed the limits for local transmit coils and shows intersubject variations of up to a factor of three. ConclusionsThe correlations between anatomy and induced local SAR are weak for normalized exposure, but strong for a fixed B1+ field, suggesting that anatomical properties could be used for fast SAR predictions. This study demonstrates that a representative virtual human population is indispensable for the investigation of local SAR levels. Magn Reson Med 71:839-845, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Murbach, Manuel; Neufeld, Esra; Kuster, Niels] ITIS Fdn, CH-8004 Zurich, Switzerland. [Murbach, Manuel; Pruessmann, Klaas P.] Univ Zurich, Inst Biomed Engn, Zurich, Switzerland. [Murbach, Manuel; Pruessmann, Klaas P.] ETH, Zurich, Switzerland. [Kainz, Wolfgang] US FDA, CDRH, Silver Spring, MD USA. [Kuster, Niels] Swiss Fed Inst Technol, Zurich, Switzerland. RP Murbach, M (reprint author), ITIS Fdn, Zeughausstr 43, CH-8004 Zurich, Switzerland. EM murbach@itis.ethz.ch FU EUREKA [E!4144]; CTI [9193.1] FX Grant sponsor: EUREKA; Grant number: E!4144. Grant sponsor: CTI; Grant number: 9193.1 (project MRI+). NR 10 TC 11 Z9 11 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD FEB PY 2014 VL 71 IS 2 BP 839 EP 845 DI 10.1002/mrm.24690 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AA0FA UT WOS:000330769700041 PM 23440667 ER PT J AU Khurana, T Collison, M Slater, JE AF Khurana, Taruna Collison, Maggie Slater, Jay E. TI Simultaneous Measurement Of Multiple Proteins In Blattella Germanica Extract Using Antibody-Based Multiplex Assay 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 FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Khurana, Taruna; Collison, Maggie] CBER FDA, Rockville, MD USA. [Slater, Jay E.] FDA CBER OVRR DBPAP, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 2014 VL 133 IS 2 SU S MA 761 BP AB220 EP AB220 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241301077 ER PT J AU Mueller, G Ankney, J Pedersen, L Khurana, T Slater, JE Glesner, J Pomes, A London, R AF Mueller, Geoffrey Ankney, John Pedersen, Lars Khurana, Taruna Slater, Jay E. Glesner, Jill Pomes, Anna London, Robert TI Epitope Mapping Of An Anti-Bla g 1 ScFv Used For Cockroach Allergen Quantitation 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 FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Mueller, Geoffrey; Ankney, John; Pedersen, Lars; London, Robert] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Khurana, Taruna] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Slater, Jay E.] US FDA, CBER, OVRR, DBPAP, Rockville, MD 20857 USA. [Glesner, Jill; Pomes, Anna] Indoor Biotechnol Inc, Charlottesville, VA USA. NR 0 TC 0 Z9 0 U1 0 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 2014 VL 133 IS 2 SU S MA 348 BP AB100 EP AB100 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241300346 ER PT J AU Oladipo, TM Luccioli, S AF Oladipo, Taiye M. Luccioli, Stefano TI Prevalence and Characteristics of Consumer-Reported Food Allergic and Anaphylactic Events in CAERS, 2007-2011 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 FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Oladipo, Taiye M.; Luccioli, Stefano] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 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 2014 VL 133 IS 2 SU S MA 718 BP AB207 EP AB207 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241301034 ER PT J AU Slater, JE Zoch, A Newman-Gerhardt, S Khurana, T AF Slater, Jay E. Zoch, Allison Newman-Gerhardt, Shoshana Khurana, Taruna TI Comparison Of Total Protein Profile Of Alternaria Alternata Extract Obtained From Various US Allergenic Extract Manufacturers 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 FEB 28-MAR 04, 2014 CL San Diego, CA SP Amer Acad Allergy Asthma & Immunol C1 [Slater, Jay E.] US FDA, CBER, OVRR, DBPAP, Rockville, MD 20857 USA. [Zoch, Allison; Newman-Gerhardt, Shoshana] US FDA, CBER, Rockville, MD 20857 USA. [Khurana, Taruna] CBER FDA, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 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 2014 VL 133 IS 2 SU S MA 346 BP AB100 EP AB100 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 297FO UT WOS:000330241300344 ER PT J AU Denne, JS Pennello, G Zhao, LP Chang, SC Althouse, S AF Denne, Jonathan S. Pennello, Gene Zhao, Luping Chang, Shao-Chun Althouse, Sandra TI Identifying a Subpopulation for a Tailored Therapy: Bridging Clinical Efficacy From a Laboratory-Developed Assay to a Validated In Vitro Diagnostic Test Kit SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH LA English DT Article DE Agreement; Companion diagnostic; Concordance; Oncology; Pharmacogenomics; Predictive biomarker ID MISSING DATA; TRIALS; CHALLENGES; IMPUTATION AB In the United States, regulatory approval of a therapy that is tailored to a subpopulation may require the coapproval of a companion in vitro diagnostic (IVD) tool for identifying that subpopulation. Unfortunately, for many reasons, development of the companion IVD may lag such that it is unavailable during a pivotal clinical trial of the therapy. Instead, a laboratory-developed test (LDT) may be used on clinical trial specimens to identify the subpopulation on whom to evaluate the therapy. However, remaining specimen material is saved so that when the companion IVD is ready for market, the specimens can be retested, in an effort to "bridge" from the LDT to the IVD. Unfortunately, retest results can be missing or invalid because some subjects lack remaining specimen material or because what remains is unevaluable (e.g., due to insufficient specimen material, inadequate specimen quality). We frame the bridging analysis problem as one of estimating drug efficacy in the IVD-defined subpopulation. We develop a closed-form approach, as well as approaches based on multiple imputation and bootstrapping to address the missing data problem. We discuss this in the context of a case study involving a recent submission and approval in the United States of a drug and IVD in oncology. C1 [Denne, Jonathan S.; Zhao, Luping; Chang, Shao-Chun] Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. [Pennello, Gene] US FDA, Diagnost Devices Branch, Div Biostat, OSB,CDRH, Silver Spring, MD 20993 USA. [Althouse, Sandra] IUPUI, Dept Biostat, Indianapolis, IN 46202 USA. RP Denne, JS (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. EM jon_denne@lilly.com; gene.pennello@fda.hhs.gov; zhao_luping@lilly.com; chang_shao-chun@lilly.com; salhous@iupui.edu NR 22 TC 5 Z9 5 U1 1 U2 5 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 FEB PY 2014 VL 6 IS 1 BP 78 EP 88 DI 10.1080/19466315.2013.852618 PG 11 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 299YJ UT WOS:000330431300008 ER PT J AU Uribarri, J Calvo, MS AF Uribarri, Jaime Calvo, Mona S. TI Dietary phosphorus intake and health SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material ID DISEASE C1 [Uribarri, Jaime] Mt Sinai Sch Med, New York, NY USA. [Calvo, Mona S.] US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, US Dept HHS, Laurel, MD USA. RP Uribarri, J (reprint author), 1 Gustave Levy Pl, New York, NY 10029 USA. EM jaime.uribarri@mssm.edu NR 10 TC 3 Z9 3 U1 0 U2 8 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 2014 VL 99 IS 2 BP 247 EP 248 DI 10.3945/ajcn.113.080259 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 295XR UT WOS:000330150200002 PM 24381089 ER PT J AU Khurana, T Collison, M Chew, FT Slater, JE AF Khurana, Taruna Collison, Maggie Chew, Fook Tim Slater, Jay E. TI Bla g 3: a novel allergen of German cockroach identified using cockroach-specific avian single-chain variable fragment antibody SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID INNER-CITY CHILDREN; BLATTELLA-GERMANICA; RISK-FACTORS; ASTHMA; EXTRACTS; EXPOSURE; IGE; SENSITIZATION; PROTEINS; HYPERSENSITIVITY AB Background: The IgE response to cockroach allergens is thought to be associated with asthma. German cockroach (GCr) allergen extract is a complex mixture of allergens, and the identification and characterization of immunodominant allergens is important for the effective diagnosis and treatment of GCr-induced asthma. Objective: To characterize a novel GCr allergen homologous to the American cockroach allergen Per a 3. Methods: GCr-specific avian monoclonal antibodies were used for direct immunoprecipitation of specific targets from whole-body GCr extract. Precipitated protein was identified by mass spectrometry and sequence analysis. Putative recombinant protein also was expressed, purified, and used for determination of allergenicity, determined by IgE enzyme-linked immunosorbent assay with serum from 61 GCr-allergic patients. The identified target also was analyzed for heat stability using a bead-based assay. Results: The immunoprecipitated target of monoclonal antibody 2A1 was identified as a novel allergen of GCr homologous to American cockroach allergen Per a 3. This homolog, designated Bla g 3, has an apparent mass of 78 kDa, can be measured in GCr extract using antibody 2A1, and is a heat-stable protein. Screening of 61 serum samples from GCr-allergic patients showed a 22% prevalence of Bla g 3-specific IgE. Conclusion: Bla g 3 is a GCr allergen with structural homology to American cockroach allergen Per a 3. (C) 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. C1 [Khurana, Taruna; Collison, Maggie; Slater, Jay E.] US FDA, Lab Immunobiochem, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20014 USA. [Chew, Fook Tim] Natl Univ Singapore, Dept Biol Sci, Allergy & Mol Immunol Lab, Singapore 117548, Singapore. RP Slater, JE (reprint author), FDA CBER, 1401 Rockville Pike HFM-422, Rockville, MD 20850 USA. EM jay.slater@fda.hhs.gov RI Chew, Fook Tim/E-7259-2010 OI Chew, Fook Tim/0000-0003-1337-5146 FU Center for Biologics Evaluation and Research, US Food and Drug Administration FX This work was supported by intramural funding from Center for Biologics Evaluation and Research, US Food and Drug Administration. NR 34 TC 9 Z9 9 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 EI 1534-4436 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD FEB PY 2014 VL 112 IS 2 BP 140 EP + DI 10.1016/j.anai.2013.11.007 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 296HI UT WOS:000330175500012 PM 24468254 ER PT J AU Selker, HP Oye, KA Eichler, HG Stockbridge, NL Mehta, CR Kaitin, KI McElwee, NE Honig, PK Erban, JK D'Agostino, RB AF Selker, H. P. Oye, K. A. Eichler, H-G Stockbridge, N. L. Mehta, C. R. Kaitin, K. I. McElwee, N. E. Honig, P. K. Erban, J. K. D'Agostino, R. B. TI A Proposal for Integrated Efficacy-to-Effectiveness (E2E) Clinical Trials SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; THROMBOLYTIC PREDICTIVE INSTRUMENT; TISSUE-PLASMINOGEN ACTIVATOR; BREAST-CANCER; CORONARY ANGIOPLASTY; THERAPY; STREPTOKINASE; CHEMOTHERAPY; TRASTUZUMAB; BENEFIT AB We propose an "efficacy-to-effectiveness" (E2E) clinical trial design, in which an effectiveness trial would commence seamlessly upon completion of the efficacy trial. Efficacy trials use inclusion/exclusion criteria to produce relatively homogeneous samples of participants with the target condition, conducted in settings that foster adherence to rigorous clinical protocols. Effectiveness trials use inclusion/exclusion criteria that generate heterogeneous samples that are more similar to the general patient spectrum, conducted in more varied settings, with protocols that approximate typical clinical care. in E2E trials, results from the efficacy trial component would be used to design the effectiveness trial component, to confirm and/or discern associations between clinical characteristics and treatment effects in typical care, and potentially to test new hypotheses. An E2E approach may improve the evidentiary basis for selecting treatments, expand understanding of the effectiveness of treatments in subgroups with particular clinical features, and foster incorporation of effectiveness information into regulatory processes. C1 [Selker, H. P.; Kaitin, K. I.; Erban, J. K.] Tufts Univ, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA. [Selker, H. P.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Oye, K. A.] Massachusetts Inst Technol Polit Sci & Engn Syst, Cambridge, MA USA. [Eichler, H-G] European Med Agcy, London, England. [Stockbridge, N. L.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Mehta, C. R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Kaitin, K. I.] Tufts Ctr Study Drug Dev, Boston, MA USA. [McElwee, N. E.] Merck & Co Inc, Whitehouse Stn, NJ USA. [Erban, J. K.] Tufts Canc Ctr, Boston, MA USA. [D'Agostino, R. B.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [D'Agostino, R. B.] Harvard Clin Res Inst, Boston, MA USA. RP Selker, HP (reprint author), Tufts Univ, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA. EM hselker@tuftsmedicalcenter.org FU National Center for Research Resources of the National Institutes of Health [UL1 RR025752]; National Center for Advancing Translational Sciences [UL1 TR000073] FX The authors thank Aaron Kirby for facilitating and managing this investigation and report, Abdmoain Abudabrh for very helpful background research for this project, and Muriel Powers for expert manuscript preparation. The project was supported by the National Center for Research Resources of the National Institutes of Health under grant UL1 RR025752 and the National Center for Advancing Translational Sciences under grant UL1 TR000073. The content is solely the responsibility of the authors and does not necessarily represent the official views of the European Medicines Agency, the US Food and Drug Administration, or the National Institutes of Health. NR 23 TC 8 Z9 9 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2014 VL 95 IS 2 BP 147 EP 153 DI 10.1038/clpt.2013.177 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 295YA UT WOS:000330151100019 PM 24060819 ER PT J AU Einolfl, HJ Chen, L Fahmi, OA Gibson, CR Obach, RS Shebley, M Silva, J Sinz, MW Unadkat, JD Zhang, L Zhao, P AF Einolfl, H. J. Chen, L. Fahmi, O. A. Gibson, C. R. Obach, R. S. Shebley, M. Silva, J. Sinz, M. W. Unadkat, J. D. Zhang, L. Zhao, P. TI Evaluation of Various Static and Dynamic Modeling Methods to Predict Clinical CYP3A Induction Using In Vitro CYP3A4 mRNA Induction Data SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID DRUG-DRUG INTERACTIONS; CYTOCHROME-P450 3A ACTIVITY; ORAL MIDAZOLAM; NIFEDIPINE PHARMACOKINETICS; PLASMA-CONCENTRATIONS; HUMAN HEPATOCYTES; ENZYME-INDUCTION; VIVO; HUMANS; RIFAMPIN AB Several drug-drug interaction (DDI) prediction models were evaluated for their ability to identify drugs with cytochrome P450 (CYP)3A induction liability based on in vitro mRNA data. The drug interaction magnitudes of CYP3A substrates from 28 clinical trials were predicted using (i) correlation approaches (ratio of the in vivo peak plasma concentration (C-max) to in vitro half-maximal effective concentration (EC50); and relative induction score), (ii) a basic static model (calculated R-3 value), (iii) a mechanistic static model (net effect), and (iv) mechanistic dynamic (physiologically based pharmacokinetic) modeling. All models performed with high fidelity and predicted few false negatives or false positives. The correlation approaches and basic static model resulted in no false negatives when total C-max was incorporated; these models may be sufficient to conservatively identify clinical CYP3A induction liability. Mechanistic models that include CYP inactivation in addition to induction resulted in DDI predictions with less accuracy, likely due to an overprediction of the inactivation effect. C1 [Einolfl, H. J.] Novartis, E Hanover, NJ USA. [Chen, L.] GlaxoSmithKline, King Of Prussia, PA USA. [Fahmi, O. A.; Obach, R. S.] Pfizer Inc, Groton, CT 06340 USA. [Gibson, C. R.] Merck Res Labs, West Point, PA USA. [Shebley, M.] AbbVie Inc, N Chicago, IL USA. [Silva, J.] Johnson &Johnson Pharmaceut Res Inst, Raritan, NJ USA. [Sinz, M. W.] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Unadkat, J. D.] Univ Washington, Seattle, WA 98195 USA. [Zhang, L.; Zhao, P.] US FDA, Silver Spring, MD USA. RP Einolfl, HJ (reprint author), Novartis, E Hanover, NJ USA. EM heidi.einolf@novartis.com; Odette.a.fahmi@pfizer.com RI Shebley, Mohamad/G-1368-2016 OI Shebley, Mohamad/0000-0002-0147-8933 NR 36 TC 24 Z9 24 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2014 VL 95 IS 2 BP 179 EP 188 DI 10.1038/clpt.2013.170 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 295YA UT WOS:000330151100022 PM 23995268 ER PT J AU Vieiral, MLT Kirby, B Ragueneau-Majlessi, I Galetin, A Chien, JYL Einolf, HJ Fahmi, OA Fischer, V Fretland, A Grime, K Hall, SD Higgs, R Plowchalk, D Riley, R Seibert, E Skordos, K Snoeys, J Venkatakrishnan, K Waterhouse, T Obach, RS Berglund, EG Zhang, L Zhao, P Reynolds, KS Huang, SM AF Vieiral, Md L. T. Kirby, B. Ragueneau-Majlessi, I. Galetin, A. Chien, J. Y. L. Einolf, H. J. Fahmi, O. A. Fischer, V. Fretland, A. Grime, K. Hall, S. D. Higgs, R. Plowchalk, D. Riley, R. Seibert, E. Skordos, K. Snoeys, J. Venkatakrishnan, K. Waterhouse, T. Obach, R. S. Berglund, E. G. Zhang, L. Zhao, P. Reynolds, K. S. Huang, S-M TI Evaluation of Various Static In Vitro-In Vivo Extrapolation Models for Risk Assessment of the CYP3A Inhibition Potential of an Investigational Drug SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CYTOCHROME-P450 INHIBITION; PARALLEL PATHWAYS; PREDICTION; INACTIVATION; ELIMINATION; IMPACT; METABOLISM; ALGORITHMS; ENZYMES AB Nine static models (seven basic and two mechanistic) and their respective cutoff values used for predicting cytochrome P450 3A (CYP3A) inhibition, as recommended by the US Food and Drug Administration and the European Medicines Agency, were evaluated using data from 119 clinical studies with orally administered midazolam as a substrate. Positive predictive error (PPE) and negative predictive error (NPE) rates were used to assess model performance, based on a cutoff of 1.25-fold change in midazolam area under the curve (AUC) by inhibitor. For reversible inhibition, basic models using total or unbound systemic inhibitor concentration [I] had high NPE rates (46-47%), whereas those using intestinal luminal ([I](gut)) values had no NPE but a higher PPE. All basic models for time-dependent inhibition had no NPE and reasonable PPE rates (15-18%). Mechanistic static models that incorporate all interaction mechanisms and organ specific [I] values (enterocyte and hepatic inlet) provided a higher predictive precision, a slightly increased NPE, and a reasonable PPE. Various cutoffs for predicting the likelihood of CYP3A inhibition were evaluated for mechanistic models, and a cutoff of 1.25-fold change in midazolam AUC appears appropriate. C1 [Vieiral, Md L. T.; Zhang, L.; Zhao, P.; Reynolds, K. S.; Huang, S-M] US FDA, Silver Spring, MD USA. [Kirby, B.; Ragueneau-Majlessi, I.] Univ Washington, Seattle, WA 98195 USA. [Galetin, A.] Univ Manchester, Manchester, England. [Chien, J. Y. L.; Fretland, A.; Hall, S. D.; Higgs, R.; Waterhouse, T.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Einolf, H. J.] Novartis, E Hanover, NJ USA. [Fahmi, O. A.; Plowchalk, D.; Obach, R. S.] Pfizer Inc, Groton, CT 06340 USA. [Fischer, V.] AbbVie, N Chicago, IL USA. [Grime, K.] AstraZeneca Res & Dev, Molndal, Sweden. [Riley, R.] AstraZeneca Res & Dev, Alderley Pk, England. [Seibert, E.] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. [Skordos, K.] GlaxoSmithKline, Res Triangle Pk, NC USA. [Snoeys, J.] Janssen Pharmaceut Co Johnson &Johnson, Beerse, Belgium. [Venkatakrishnan, K.] Millennium Pharmaceut Inc, Cambridge, MA USA. [Berglund, E. G.] Med Prod Agcy, Uppsala, Sweden. RP Zhao, P (reprint author), US FDA, Silver Spring, MD USA. EM chien_jenny_yuehling@lilly.com; heidi.einolf@novartis.com; ping.zhao@fda.hhs.gov; ShiewMei.Huang@fda.hhs.gov OI Galetin, Aleksandra/0000-0002-3933-5217 FU CAPES/Full:night program; US Food and Drug Administration (FDA) Critical Path Initiative Project "Development of an Internal Drug Interaction Database"; Research Participation Program at the Center for Drug Evaluation and Research FX We acknowledge the CAPES/Full:night program for the doctoral scholarship of M.d.L.T.V. and the US Food and Drug Administration (FDA) Critical Path Initiative Project "Development of an Internal Drug Interaction Database." This work was supported in part by an appointment 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 US Department of Energy and the FDA. We acknowledge Tim Waterhouse and Richard Higgs, of Eli Lilly and Company, for providing expert support for the error rate analyses. No official support or endorsement by the Medical Products Agency is intended or should be inferred. NR 33 TC 20 Z9 20 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2014 VL 95 IS 2 BP 189 EP 198 DI 10.1038/clpt.2013.187 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 295YA UT WOS:000330151100023 PM 24048277 ER PT J AU Jarow, JP Lerner, SP Kluetz, PG Liu, K Sridhara, R Bajorin, D Chang, S Dinney, CPN Groshen, S Morton, RA O'Donnell, M Quale, DZ Schoenberg, M Seigne, J Vikram, B AF Jarow, Jonathan P. Lerner, Seth P. Kluetz, Paul G. Liu, Ke Sridhara, Rajeshwari Bajorin, Dean Chang, Sam Dinney, Colin P. N. Groshen, Susan Morton, Ronald A. O'Donnell, Michael Quale, Diane Zipursky Schoenberg, Mark Seigne, John Vikram, Bhadrasain TI Clinical Trial Design for the Development of New Therapies for Nonmuscle-invasive Bladder Cancer: Report of a Food and Drug Administration and American Urological Association Public Workshop SO UROLOGY LA English DT Article ID CARCINOMA IN-SITU; HEXAMINOLEVULINATE FLUORESCENCE CYSTOSCOPY; GUERIN PLUS INTERFERON; WHITE-LIGHT CYSTOSCOPY; INTRAVESICAL THERAPY; UROTHELIAL CARCINOMA; PHASE-III; MULTICENTER; CYSTECTOMY; RECURRENCE AB OBJECTIVE To summarize the discussion at a public workshop, cosponsored by the U.S. Food and Drug Administration (FDA) and the American Urological Association, reviewing potential trial designs for the development of new therapies for non-muscle-invasive bladder cancer (NMIBC). There have been only 3 drug approvals for NMIBC in the last 30 years, and product development for this disease has been stymied by difficulties in trial design and patient accrual. METHODS A workshop evaluating potential trial design for the development of therapies for NMIBC was held in San Diego, CA, in May 2013. Invited experts representing all stakeholders, including urology, medical oncology, radiation oncology, industry, and patient advocates, discussed development of products for all risk strata of NMIBC. RESULTS The panel responded to specific questions from the FDA, discussing eligibility criteria, efficacy endpoints, and trial design for patients with a mix of high-grade papillary disease and carcinoma in situ, Bacillus Calmette-Guerin (BCG)-refractory disease, and intermediate-risk disease. Panel members also addressed the magnitude of response that would be clinically meaningful for various disease strata and trial design options for perioperative intravesical chemotherapy instillation at the time of resection of bladder tumors. CONCLUSION Expert commentary provided by panel members will inform a planned FDA guidance on pathways for drug and biologic development for NMIBC and will be discussed at meetings of the FDA's Oncologic Drugs Advisory Committee. FDA intends to develop a set of principles that can be used to promote the development of new products for this disease. Published by Elsevier Inc. C1 [Jarow, Jonathan P.] US FDA, Off Hematol & Oncol Prod, Silver Spring, MD 20993 USA. Baylor Coll Med, Scott Dept Urol, Med Ctr, Houston, TX 77030 USA. US FDA, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA. US FDA, Div Biometr 5, Off Biostat, CDER, Silver Spring, MD 20993 USA. Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, New York, NY USA. Vanderbilt Univ, Med Ctr, Dept Urol Surg, Nashville, TN USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. USC Keck Sch Med, USC Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA USA. Amer Med Syst, Minnetonka, MN USA. Univ Iowa, Iowa City, IA USA. Bladder Canc Advocacy Network, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Norris Cotton Canc Ctr, Lebanon, NH USA. NCI, Bethesda, MD 20892 USA. RP Jarow, JP (reprint author), US FDA, Off Hematol & Oncol Prod, Silver Spring, MD 20993 USA. EM Jonathan.jarow@fda.hhs.gov FU NCI NIH HHS [P30 CA016672] NR 14 TC 8 Z9 8 U1 1 U2 3 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 2014 VL 83 IS 2 BP 262 EP 264 DI 10.1016/j.urology.2013.10.030 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 296ZF UT WOS:000330223600002 PM 24332121 ER PT J AU Liang, XY Pfeiffer, RM Li, WQ Brossard, M Burke, LS Wheeler, W Calista, D Fargnoli, MC Ghiorzo, P Peris, K Bianchi-Scarra, G Chaudru, V Zelenika, D Maederl, D Burdette, L Yeager, M Chanock, S Landi, MT Demenais, F Tucker, MA Goldstein, AM Yang, XHR AF Liang, Xueying Pfeiffer, Ruth M. Li, Wen-Qing Brossard, Myriam Burke, Laura S. Wheeler, William Calista, Donato Fargnoli, Maria Concetta Ghiorzo, Paola Peris, Ketty Bianchi-Scarra, Giovanna Chaudru, Valerie Zelenika, Diana Maederl, Dennis Burdette, Laurie Yeager, Meredith Chanock, Stephen Landi, Maria Teresa Demenais, Florence Tucker, Margaret A. Goldstein, Alisa M. Yang, Xiaohong R. TI Association of Genetic Variants in CDK6 and XRCC1 with the Risk of Dysplastic Nevi in Melanoma-Prone Families SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID DNA-REPAIR; MEDITERRANEAN POPULATION; CUTANEOUS MELANOMA; CDKN2A MUTATIONS; POLYMORPHISMS; MC1R; CANCER; PENETRANCE; ASIP AB Dysplastic nevi (DN) is a strong risk factor for cutaneous malignant melanoma (CMM), and it frequently occurs in melanoma-prone families. To identify genetic variants for DN, we genotyped 677 tagSNPs in 38 melanoma candidate genes that are involved in pigmentation, DNA repair, cell cycle control, and melanocyte proliferation pathways in a total of 504 individuals (310 with DN, 194 without DN) from 53 melanoma-prone families (23 CDKN2A mutation positive and 30 negative). Conditional logistic regression, conditioning on families, was used to estimate the association between DN and each single-nucleotide polymorphism (SNP) separately, adjusted for age, sex, CMM, and CDKN2A status. P-values for SNPs in the same gene were combined to yield gene-specific P-values. Two genes, CDK6 (cyclin-dependent kinase 6) and XRCC1, were significantly associated with DN after Bonferroni correction for multiple testing (P=0.0001 and 0.00025, respectively), whereas neither gene was significantly associated with CMM. Associations for CDK6 SNPs were stronger in CDKN2A mutation-positive families (rs2079147, P-interaction = 0.0033), whereas XRCC1 SNPs had similar effects in mutation-positive and -negative families. The association for one of the associated SNPs in XRCC1 (rs25487) was replicated in two independent data sets (random-effect meta-analysis: P<0.0001). Our findings suggest that some genetic variants may contribute to DN risk independently of their association with CMM in melanoma-prone families. C1 [Liang, Xueying; Pfeiffer, Ruth M.; Li, Wen-Qing; Burke, Laura S.; Maederl, Dennis; Burdette, Laurie; Yeager, Meredith; Chanock, Stephen; Landi, Maria Teresa; Tucker, Margaret A.; Goldstein, Alisa M.; Yang, Xiaohong R.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Liang, Xueying] US FDA, Off In Vitro Diagnost & Radiol Hlth, CDRH, Silver Spring, MD USA. [Brossard, Myriam; Chaudru, Valerie; Demenais, Florence] INSERM, UMR 946, Genet Variat & Human Dis Unit, Paris, France. [Brossard, Myriam; Chaudru, Valerie; Demenais, Florence] Univ Paris Diderot, Sorbonne Paris Cite, Inst Univ Hematol, Paris, France. [Brossard, Myriam] Univ Paris Sud, F-94275 Le Kremlin Bicetre, France. [Wheeler, William] Informat Management Serivces Inc, Rockville, MD USA. [Calista, Donato] Osped Gen Provinciale M Bufalini, Dept Dermatol, Cesena, Italy. [Fargnoli, Maria Concetta; Peris, Ketty] Univ Aquila, Dept Dermatol, I-67100 Laquila, Italy. [Ghiorzo, Paola; Bianchi-Scarra, Giovanna] Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy. [Ghiorzo, Paola; Bianchi-Scarra, Giovanna] IRCCS AOU San Martino IST, Lab Genet Rare Hereditary Canc, Genoa, Italy. [Chaudru, Valerie] Univ Evry Val dEssone, Evry, France. [Zelenika, Diana] CEA, Inst Genom, Ctr Natl Genotypage, Evry, France. RP Yang, XHR (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM Royang@mail.nih.gov RI Demenais, Florence/G-3298-2013; Li, Wenqing/N-2293-2014; Tucker, Margaret/B-4297-2015; OI Demenais, Florence/0000-0001-8361-0936; Li, Wenqing/0000-0002-1283-4091; Peris, Ketty/0000-0002-5237-0463; Fargnoli, Maria Concetta/0000-0002-7249-2556 FU National Institutes of Health (NIH), National Cancer Institute (NCI); Division of Cancer Epidemiology and Genetics (DCEG); Ligue Nationale Contre le Cancer [PRE O5/FD, PRE 09/FD]; NIH, NCI, DCEG; NIH [CA 5558-01A2] FX We are indebted to the participating families, whose generosity and cooperation have made this study possible. We also acknowledge the contributions to this work that were made by Virginia Pichler, Deborah Zametkin, and Mary Fraser. This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI), and Division of Cancer Epidemiology and Genetics (DCEG). The French study was partly funded by Ligue Nationale Contre le Cancer (PRE O5/FD and PRE 09/FD to FD and Doctoral fellowship to MB). We thank the French NEVRISK study group that includes clinicians from Hopital Saint-Louis, Fondation Rothschild, and Institut Gustave Roussy for their contribution to patient recruitment and data collection. The Italian studies were supported by the Intramural Research Program of NIH, NCI, DCEG, and by R01 grant (CA 5558-01A2) from the NIH to MTL. NR 25 TC 4 Z9 4 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 2014 VL 134 IS 2 BP 481 EP 487 DI 10.1038/jid.2013.316 PG 7 WC Dermatology SC Dermatology GA 292IS UT WOS:000329896000027 PM 23892592 ER PT J AU Myers, MB McKim, KL Parsons, BL AF Myers, Meagan B. McKim, Karen L. Parsons, Barbara L. TI A Subset of Papillary Thyroid Carcinomas Contain KRAS Mutant Subpopulations at Levels Above Normal Thyroid SO MOLECULAR CARCINOGENESIS LA English DT Article DE ACB-PCR; cancer biomarkers; cancer genetics; mutation; oncogenes ID ACB-PCR QUANTIFICATION; RAF INHIBITORS; BRAF MUTATIONS; CANCER; TUMOR; PATHWAY; GROWTH; ACTIVATION; EXPOSURE; FRACTION AB The molecular pathogenesis of papillary thyroid carcinoma (PTC) is largely attributed to chromosomal rearrangements and point mutations in genes within the MAPK pathway (i.e., BRAF and RAS). Despite KRAS being the 6th most frequently mutated gene for all cancers, the reported frequency in thyroid cancer is only 2%. This may be due, in part, to the use of insensitive mutation detection methods such as DNA sequencing. Therefore, using the sensitive and quantitative ACB-PCR approach, we quantified KRAS codon 12 GGTGAT and GGTGTT mutant fraction (MF) in 20 normal thyroid tissues, 17 primary PTC, 2 metastatic PTC, and 1 anaplastic thyroid carcinoma. We observed measurable levels of KRAS codon 12 GAT or GTT mutation in all normal thyroid tissues. For PTCs, 29.4% and 35.3% had KRAS codon 12 GAT and GTT MF above the 95% upper confidence interval for the corresponding MFs in normal thyroid. The highest observed KRAS codon 12 GTT MFs were associated with tumors with follicular characteristics and relatively high levels of tumor necrosis. The results indicate KRAS mutant subpopulations are present in a large number of thyroid tumors, a fact previously unrecognized. The presence of KRAS mutation may indicate a tumor with an aggressive phenotype, thus directing the course of clinical treatment. (c) 2012 Wiley Periodicals, Inc. C1 [Myers, Meagan B.; McKim, Karen L.; Parsons, Barbara L.] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Myers, MB (reprint author), Div Genet & Mol Toxicol, HFT 120,3900,NCTR Rd, Jefferson, AR 72079 USA. FU NIH [5 U42 RR006042]; National Center for Toxicological Research; U.S. Food & Drug Administration FX The authors thank Drs. James Fuscoe and Deborah Hanson for their critical review of this manuscript. Tissue samples were provided by the Cooperative Human Tissue Network, a National Cancer Institute supported resource. Other investigators may have received samples from these same tissue specimens. We acknowledge use of tissues procured by the National Disease Research Interchange (NDRI; with support from NIH grant 5 U42 RR006042). The contents of this manuscript do not necessarily reflect the views or policies of the U.S. Food & Drug Administration, nor does the mention of trade names or commercial products constitute endorsement or recommendation for use. This study was supported by National Center for Toxicological Research and U.S. Food & Drug Administration. NR 35 TC 11 Z9 11 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0899-1987 EI 1098-2744 J9 MOL CARCINOGEN JI Mol. Carcinog. PD FEB PY 2014 VL 53 IS 2 BP 159 EP 167 DI 10.1002/mc.21953 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 292UB UT WOS:000329926900008 PM 22930660 ER PT J AU Wysowski, DK AF Wysowski, Diane K. TI Reply to: Effect of pharmacological treatment of osteoporosis in the prevention of pathological vertebral fractures SO BONE LA English DT Letter C1 US FDA, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP Wysowski, DK (reprint author), US FDA, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. NR 5 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 EI 1873-2763 J9 BONE JI Bone PD FEB PY 2014 VL 59 BP 150 EP 150 DI 10.1016/j.bone.2013.11.003 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 287QZ UT WOS:000329558600020 PM 24252522 ER PT J AU Prabhakar, S Asuthkar, S Lee, W Chigurupati, S Zakharian, E Tsung, AJ Velpula, KK AF Prabhakar, Sheila Asuthkar, Swapna Lee, William Chigurupati, Srinivasulu Zakharian, Eleonora Tsung, Andrew J. Velpula, Kiran Kumar TI Targeting DUSPs in glioblastomas - wielding a double-edged sword? SO CELL BIOLOGY INTERNATIONAL LA English DT Article DE brain; nervous system; cancer; tumor suppressor ID PROTEIN-KINASE PHOSPHATASE-1; DUAL-SPECIFICITY PHOSPHATASES; DIRECT TRANSCRIPTIONAL TARGET; CANDIDATE TUMOR-SUPPRESSOR; CELL-ACTIVE INHIBITOR; HUMAN BREAST-CANCER; MAP-KINASE; TYROSINE PHOSPHATASES; PANCREATIC-CANCER; DOWN-REGULATION AB Several dual-specificity phosphatases (DUSPs) that play key roles in the direct or indirect inactivation of different MAP kinases (MAPKs) have been implicated in human cancers over the past decade. This has led to a growing interest in identifying DUSPs and their specific inhibitors for further testing and validation as therapeutic targets in human cancers. However, the lack of understanding of the complex regulatory mechanisms and cross-talks between MAPK signaling pathways, combined with the fact that DUSPs can act as a double-edged sword in cancer progression, calls for a more careful and thorough investigation. Among the various types of brain cancer, glioblastoma multiforme (GBM) is notorious for its aggressiveness and resistance to current treatment modalities. This has led to the search for new molecular targets, particularly those involving various signaling pathways. DUSPs appear to be a promising target, but much more information on DUSP targets and their effects on GBM is needed before potential therapies can be developed, tested, and validated. This review identifies and summarize the specific roles of DUSP1, DUSP4, DUSP6 and DUSP26 that have been implicated in GBM. C1 [Asuthkar, Swapna; Lee, William; Zakharian, Eleonora; Tsung, Andrew J.; Velpula, Kiran Kumar] Univ Illinois, Coll Med Peoria, Dept Canc Biol & Pharmacol, Peoria, IL 61605 USA. [Prabhakar, Sheila] Southeastern Univ, Dept Nat & Hlth Sci, Lakeland, FL 33801 USA. [Chigurupati, Srinivasulu] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Velpula, KK (reprint author), Univ Illinois, Coll Med Peoria, Dept Canc Biol & Pharmacol, 1 Illini Dr, Peoria, IL 61605 USA. EM velpula@uic.edu NR 80 TC 6 Z9 6 U1 1 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-6995 EI 1095-8355 J9 CELL BIOL INT JI Cell Biol. Int. PD FEB PY 2014 VL 38 IS 2 BP 145 EP 153 DI 10.1002/cbin.10201 PG 9 WC Cell Biology SC Cell Biology GA 288DB UT WOS:000329591100001 PM 24155099 ER PT J AU Martinez, MN AF Martinez, M. N. TI Bioequivalence accomplishments, ongoing initiatives, and remaining challenges SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Review ID HIGHLY VARIABLE DRUGS; PRODUCT BIOEQUIVALENCE; RELEASE FORMULATIONS; DISSOLUTION; BIOAVAILABILITY; CLASSIFICATION; SOLUBILITY; ABSORPTION; MODELS AB Although bioequivalence (BE) concepts date back to the late 1960s, there has been a steady evolution in the tools applied to the assessment of product comparability. Despite these advancements, we continue to face a multitude of unresolved challenges. Several of these challenges are unique to veterinary medicine due to issues such as multiple species approvals, unique dosage forms (e.g., intramammary infusion and medicated premixes), physiological challenges (e.g., limitations in blood volume and stress reactions), and the need to evaluate product equivalence for products intended to release drug over a duration of months. Thus, while in some instances, we can adopt advancements implemented by our human health counterparts but in other situations, we need to pioneer our own method for resolving these challenges. The purpose of this manuscript is to provide an update on recent advances, achievements, and ongoing initiatives associated with the assessment of product BE in veterinary medicine. This review reflects the highlights of a presentation given at the 2012 meeting of the European Association for Veterinary Pharmacology and Toxicology. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Martinez, MN (reprint author), US FDA, Ctr Vet Med, HFV 100, Rockville, MD 20855 USA. EM marilyn.martinez@fda.hhs.gov NR 37 TC 3 Z9 3 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0140-7783 EI 1365-2885 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD FEB PY 2014 VL 37 IS 1 BP 2 EP 12 DI 10.1111/jvp.12063 PG 11 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 286WG UT WOS:000329499400003 PM 23841644 ER PT J AU Martinez, M Blondeau, J Cerniglia, CE Fink-Gremmels, J Guenther, S Hunter, RP Li, XZ Papich, M Silley, P Soback, S Toutain, PL Zhang, Q AF Martinez, M. Blondeau, J. Cerniglia, C. E. Fink-Gremmels, J. Guenther, S. Hunter, R. P. Li, X. -Z. Papich, M. Silley, P. Soback, S. Toutain, P. -L. Zhang, Q. TI Workshop report: The 2012 Antimicrobial Agents in Veterinary Medicine: exploring the consequences of antimicrobial drug use: a 3-D approach SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID MUTANT PREVENTION CONCENTRATIONS; RESISTANT STAPHYLOCOCCUS-AUREUS; HUMAN INTESTINAL MICROFLORA; ESCHERICHIA-COLI; SUBINHIBITORY CONCENTRATIONS; STREPTOCOCCUS-PNEUMONIAE; BIOFILM FORMATION; SELECTION WINDOW; ANTIBIOTICS; IMPACT AB Antimicrobial resistance is a global challenge that impacts both human and veterinary health care. The resilience of microbes is reflected in their ability to adapt and survive in spite of our best efforts to constrain their infectious capabilities. As science advances, many of the mechanisms for microbial survival and resistance element transfer have been identified. During the 2012 meeting of Antimicrobial Agents in Veterinary Medicine (AAVM), experts provided insights on such issues as use vs. resistance, the available tools for supporting appropriate drug use, the importance of meeting the therapeutic needs within the domestic animal health care, and the requirements associated with food safety and food security. This report aims to provide a summary of the presentations and discussions occurring during the 2012 AAVM with the goal of stimulating future discussions and enhancing the opportunity to establish creative and sustainable solutions that will guarantee the availability of an effective therapeutic arsenal for veterinary species. C1 [Martinez, M.] US FDA, Ctr Vet Med, Rockville, MD 20857 USA. [Blondeau, J.] Univ Saskatchewan, Saskatoon, SK, Canada. [Cerniglia, C. E.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Fink-Gremmels, J.] Univ Utrecht, Div Pharmacol, Inst Risk Assessment Sci, Utrecht, Netherlands. [Guenther, S.] Free Univ Berlin, Inst Microbiol & Epizoot, Fac Vet, Berlin, Germany. [Hunter, R. P.] Elanco Anim Hlth, Greenfield, IN USA. [Li, X. -Z.] Hlth Canada, Vet Drugs Directorate, Ottawa, ON K1A 0L2, Canada. [Papich, M.] N Carolina State Univ, Coll Vet Med, Raleigh, NC USA. [Silley, P.] Univ Bradford, MB Consult Ltd, Bradford BD7 1DP, W Yorkshire, England. [Soback, S.] Minist Agr, Kimron Vet Inst, Natl Residue Control Lab, Bet Dagan, Israel. [Toutain, P. -L.] Ecole Natl Vet Toulouse, INRA, UMR1331, Toulouse, France. [Zhang, Q.] Iowa State Univ, Coll Vet Med, Ames, IA USA. RP Martinez, M (reprint author), US FDA, Ctr Vet Med, Off New Anim Drug Evaluat HFV 100, Rockville, MD 20855 USA. EM Marilyn.Martinez@fda.hhs.gov RI Toutain, Pierre-Louis/G-4540-2011; Guenther, Sebastian/O-5005-2014; Hunter, Robert/A-2306-2008 OI Toutain, Pierre-Louis/0000-0002-8846-8892; Guenther, Sebastian/0000-0003-0173-7314; Hunter, Robert/0000-0003-1224-2376 NR 76 TC 3 Z9 3 U1 2 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0140-7783 EI 1365-2885 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD FEB PY 2014 VL 37 IS 1 BP E1 EP E16 DI 10.1111/jvp.12104 PG 16 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 286WG UT WOS:000329499400002 PM 24387782 ER PT J AU Horton, J Degheidy, H Bauer, S Robey, P Holmbeck, K AF Horton, Jason Degheidy, Heba Bauer, Steven Robey, Pamela Holmbeck, Kenn TI Regulation of skeletal stem cell multipotency by MT1-MMP. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-15, 2014 CL Houston, TX SP Amer Soc Bone & Mineral Res C1 [Horton, Jason] NCI, NIH, Bethesda, MD 20892 USA. [Degheidy, Heba; Bauer, Steven] US FDA, Lab Stem Cell Biol, Div Cell & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Robey, Pamela; Holmbeck, Kenn] Natl Inst Dent & Craniofacial Res, New York, NY 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 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2014 VL 29 SU 1 MA SA0249 BP S169 EP S169 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CK9ZS UT WOS:000356598701201 ER PT J AU Rosenfeld, CS Ferguson, SA AF Rosenfeld, Cheryl S. Ferguson, Sherry A. TI Barnes Maze Testing Strategies with Small and Large Rodent Models SO Jove-Journal of Visualized Experiments LA English DT Article DE Behavior; Issue 84; spatial navigation; rats; Peromyscus; mice; intra- and extra-maze cues; learning; memory; latency; search strategy; escape motivation ID MICE PEROMYSCUS-MANICULATUS; AGE-RELATED DEFECTS; SPATIAL MEMORY; ALZHEIMERS-DISEASE; MOUSE MODEL; BISPHENOL-A; WATER-MAZE; HIPPOCAMPAL NEUROGENESIS; DEVELOPMENTAL EXPOSURE; COGNITIVE IMPAIRMENT AB Spatial learning and memory of laboratory rodents is often assessed via navigational ability in mazes, most popular of which are the water and dry-land (Barnes) mazes. Improved performance over sessions or trials is thought to reflect learning and memory of the escape cage/platform location. Considered less stressful than water mazes, the Barnes maze is a relatively simple design of a circular platform top with several holes equally spaced around the perimeter edge. All but one of the holes are false-bottomed or blind-ending, while one leads to an escape cage. Mildly aversive stimuli (e.g. bright overhead lights) provide motivation to locate the escape cage. Latency to locate the escape cage can be measured during the session; however, additional endpoints typically require video recording. From those video recordings, use of automated tracking software can generate a variety of endpoints that are similar to those produced in water mazes (e.g. distance traveled, velocity/speed, time spent in the correct quadrant, time spent moving/resting, and confirmation of latency). Type of search strategy (i.e. random, serial, or direct) can be categorized as well. Barnes maze construction and testing methodologies can differ for small rodents, such as mice, and large rodents, such as rats. For example, while extra-maze cues are effective for rats, smaller wild rodents may require intra-maze cues with a visual barrier around the maze. Appropriate stimuli must be identified which motivate the rodent to locate the escape cage. Both Barnes and water mazes can be time consuming as 4-7 test trials are typically required to detect improved learning and memory performance (e.g. shorter latencies or path lengths to locate the escape platform or cage) and/or differences between experimental groups. Even so, the Barnes maze is a widely employed behavioral assessment measuring spatial navigational abilities and their potential disruption by genetic, neurobehavioral manipulations, or drug/toxicant exposure. C1 [Rosenfeld, Cheryl S.] Univ Missouri, Biomed Sci & Bond Life Sci Ctr, Columbia, MO 65211 USA. [Ferguson, Sherry A.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. RP Rosenfeld, CS (reprint author), Univ Missouri, Biomed Sci & Bond Life Sci Ctr, Columbia, MO 65211 USA. EM rosenfeldc@missouri.edu; Sherry.Ferguson@fda.hhs.gov FU NIH [RC1 ES018195]; University of Missouri College of Veterinary Medicine; National Center for Toxicological Research/FDA [E7318]; Mizzou Advantage Grant FX The authors acknowledge Mr. Eldin Jasarevic, Mr. Scott Williams, Mr. Roger W. Meissen, Sarah A. Johnson, Dr. R. Michael Roberts, Dr. Mark R. Ellersieck, and Dr. David C. Geary at the University of Missouri, and Mr. C. Delbert Law and the animal care staff at the National Center for Toxicological Research/FDA. This work was supported by an NIH Challenge Grant to Grant to CSR (RC1 ES018195), a Mizzou Advantage Grant to (CSR and DCG), a University of Missouri College of Veterinary Medicine faculty award (CSR), and protocol E7318 at the National Center for Toxicological Research/FDA. NR 64 TC 4 Z9 4 U1 3 U2 15 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD FEB PY 2014 IS 84 AR e51194 DI 10.3791/51194 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA0JL UT WOS:000348604100049 PM 24637673 ER PT J AU Baeva, LF Lyle, DB Rios, M Langone, JJ Lightfoote, MM AF Baeva, Larissa F. Lyle, Daniel B. Rios, Maria Langone, John J. Lightfoote, Marilyn M. TI Different molecular weight hyaluronic acid effects on human macrophage interleukin 1 beta production SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE biomaterials; interleukin 1; inflammation; macrophage; hyaluronic acid ID NITRIC-OXIDE PRODUCTION; ALVEOLAR MACROPHAGES; DENDRITIC CELLS; DERMAL FILLERS; DANGER SIGNAL; IN-VITRO; OLIGOSACCHARIDES; GROWTH; LIPOPOLYSACCHARIDE; FRAGMENTS AB This study examined the effect of hyaluronan (HA) molecular weight on immune response. HA with molecular weights ranging from the unitary disaccharide unit (400 Da) up to 1.7 x 10(6) Da and with very low endotoxin contamination level (less than 0.03 EU/mg) was used. Primary human monocyte/macrophage cultures were assayed for IL-1 production under a variety of inflammatory conditions with or without HA. Under the highest inflammatory states, production of interleukin 1 (IL-1) was suppressed in the presence of high molecular weight hyaluronan (HMW-HA) and in the presence of low molecular weight hyaluronan (LMW-HA) at mg/mL concentrations. There was variability in the sensitivity of the response to HA fragments with MW below 5000 Da at micromolar concentrations. There was variability in IL-1 cytokine productions from donor to donor in unstimulated human cell cultures. This study supplements our previous published study that investigated the immunogenic effect of HA molecular weights using murine cell line RAW264.6, rat splenocytes, and rat adherent differentiated primary macrophages. These data support the hypothesis that if the amount of endotoxin is reduced to an extremely low level, LMW-HA may not directly provoke normal tissue macrophage-mediated inflammatory reactions. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 305-314, 2014. C1 [Baeva, Larissa F.; Lyle, Daniel B.; Langone, John J.; Lightfoote, Marilyn M.] US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Rios, Maria] US FDA, Lab Emerging Pathogens, Div Emerging & Transfus, Off Blood Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Baeva, LF (reprint author), US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Larissa.Baeva@fda.hhs.gov NR 43 TC 15 Z9 15 U1 2 U2 30 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1549-3296 EI 1552-4965 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD FEB PY 2014 VL 102 IS 2 BP 305 EP 314 DI 10.1002/jbm.a.34704 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 269MT UT WOS:000328246100001 PM 23533059 ER PT J AU Zhu, JQ Fan, XH Cheng, YY Agarwal, R Moore, CMV Chen, ST Tong, WD AF Zhu, Jieqiang Fan, Xiaohui Cheng, Yiyu Agarwal, Rajiv Moore, Christine M. V. Chen, Shaw T. Tong, Weida TI Chemometric Analysis for Identification of Botanical Raw Materials for Pharmaceutical Use: A Case Study Using Panax notoginseng SO PLOS ONE LA English DT Article ID CHROMATOGRAPHIC FINGERPRINTS; QUALITY-CONTROL; DISCRIMINATION; SAPONINS; ROOTS AB The overall control of the quality of botanical drugs starts from the botanical raw material, continues through preparation of the botanical drug substance and culminates with the botanical drug product. Chromatographic and spectroscopic fingerprinting has been widely used as a tool for the quality control of herbal/botanical medicines. However, discussions are still on-going on whether a single technique provides adequate information to control the quality of botanical drugs. In this study, high performance liquid chromatography (HPLC), ultra performance liquid chromatography (UPLC), capillary electrophoresis (CE) and near infrared spectroscopy (NIR) were used to generate fingerprints of different plant parts of Panax notoginseng. The power of these chromatographic and spectroscopic techniques to evaluate the identity of botanical raw materials were further compared and investigated in light of the capability to distinguishing different parts of Panax notoginseng. Principal component analysis (PCA) and clustering results showed that samples were classified better when UPLC- and HPLC-based fingerprints were employed, which suggested that UPLC- and HPLC-based fingerprinting are superior to CE- and NIR-based fingerprinting. The UPLC- and HPLC-based fingerprinting with PCA were able to correctly distinguish between samples sourced from rhizomes and main root. Using chemometrics and its ability to distinguish between different plant parts could be a powerful tool to help assure the identity and quality of the botanical raw materials and to support the safety and efficacy of the botanical drug products. C1 [Zhu, Jieqiang; Fan, Xiaohui; Cheng, Yiyu] Zhejiang Univ, Coll Pharmaceut Sci, Pharmaceut Informat Inst, Hangzhou 310003, Zhejiang, Peoples R China. [Agarwal, Rajiv; Moore, Christine M. V.] US FDA, Off New Drug Qual Assessment, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Chen, Shaw T.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Tong, Weida] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Fan, XH (reprint author), Zhejiang Univ, Coll Pharmaceut Sci, Pharmaceut Informat Inst, Hangzhou 310003, Zhejiang, Peoples R China. EM fanxh@zju.edu.cn; rajiv.agarwal@fda.hhs.gov; weida.tong@fda.hhs.gov FU US FDA; National Basic Research Program of China [2012CB518405] FX The authors thank US FDA for financial assistance given under CDER's Regulatory Science and Review Enhancement (RSR) Program to RA. Participants from Zhejiang University were partially supported by the National Basic Research Program of China (No. 2012CB518405). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 26 TC 13 Z9 16 U1 7 U2 61 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 31 PY 2014 VL 9 IS 1 AR e87462 DI 10.1371/journal.pone.0087462 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 302RF UT WOS:000330621900115 PM 24498109 ER PT J AU Vaclavik, L Krynitsky, AJ Rader, JI AF Vaclavik, Lukas Krynitsky, Alexander J. Rader, Jeanne I. TI Targeted analysis of multiple pharmaceuticals, plant toxins and other secondary metabolites in herbal dietary supplements by ultra-high performance liquid chromatography quadrupole-orbital ion trap mass spectrometry SO ANALYTICA CHIMICA ACTA LA English DT Article DE Dietary supplements; Pharmaceuticals; Plant toxins; Ultra-high performance liquid chromatography; Quadrupole-orbitrap mass spectrometer ID TRADITIONAL CHINESE MEDICINES; SYNTHETIC DRUGS; ADULTERATION; IDENTIFICATION; FOOD; FEED; MS; EXTRACTION; PESTICIDES; FIBROSIS AB In this study, an ultra-high performance liquid chromatography-quadrupole-orbital ion trap mass spectrometry (UHPLC-Q-orbitrap MS) method was developed and validated for simultaneous determination of 96 pharmaceuticals, plant toxins, and other plant secondary metabolites in herbal dietary supplements. Target analytes were extracted from samples using the QuEChERS (quick easy cheap effective rugged safe) procedure. The instrument was operated in full MS-data dependent tandem mass spectrometry (full MS-dd-MS/MS) acquisition mode which enabled collection of quantitative high resolution (HR) full mass spectral data and confirmatory HR MS/MS data in a single run. The method provided excellent selectivity in both full MS and dd-MS/MS mode. Under optimized collision energy settings, product ion spectra containing both precursor and two or more product ions were obtained for most of the analytes. Limits of detection (LODs) and limits of quantification (LOQs) for the method differed significantly for the examined matrices. LODs <= 10 mu g kg(-1) and LOQs <= 50 mu g kg(-1) were obtained for 48 to 81% of target compounds across five different matrices. With the exception of highly polar analytes, the optimized QuEChERS extraction procedure provided acceptable recoveries in the range 70%-120%. The precision of the method, characterized as the relative standard deviation (RSD, n=5), was <= 25% and <= 18% at spiking concentrations of 50 mu g kg(-1) and 500 mu g kg(-1), respectively. Because of variations in matrix effects in extracts of herbal dietary supplements that differed in composition, the method of standard additions and an approach based on dilution of matrix components followed by quantification using solvent standards were applied for quantification. The procedure was used to examine commercial dietary supplements for the 96 analytes of interest. To the best of our knowledge, this is the first report of an integrated analysis and quantification of this wide range of compounds. Published by Elsevier B.V. C1 [Vaclavik, Lukas; Krynitsky, Alexander J.; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. RP Vaclavik, L (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, 5100 Paint Branch Pkwy,HFS 717, College Pk, MD 20740 USA. EM Lukas.Vaclavik@fda.hhs.gov NR 40 TC 32 Z9 34 U1 8 U2 96 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 EI 1873-4324 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD JAN 31 PY 2014 VL 810 BP 45 EP 60 DI 10.1016/j.aca.2013.12.006 PG 16 WC Chemistry, Analytical SC Chemistry GA 291PO UT WOS:000329841100008 PM 24439505 ER PT J AU Ting, HY Li, Q Yang, H Jin, ML Zhang, MJ Ye, LJ Li, J Huang, QS Yin, DC AF Ting Huyan Li, Qi Yang, Hui Jin, Ming-Liang Zhang, Ming-Jie Ye, Lin-Jie Li, Ji Huang, Qing-Sheng Yin, Da-Chuan TI Protective effect of polysaccharides on simulated microgravity-induced functional inhibition of human NK cells SO CARBOHYDRATE POLYMERS LA English DT Article DE Polysaccharide; Human natural killer (NK) cell; Cytotoxicity; Simulated microgravity (SMG) ID NATURAL-KILLER-CELLS; SPACE-FLIGHT; CYTOKINE PRODUCTION; GRIFOLA-FRONDOSA; D-FRACTION; RECEPTOR; TOLL; TLR4; GENE; CYTOTOXICITY AB Polysaccharides are believed to be strong immunostimulants that can promote the proliferation and activity of T cells, B cells, macrophages and natural killer (NK) cells. This study aimed to investigate the effects of five polysaccharides (Grifola frondosa polysaccharide (GFP), lentinan (LNT), G. lucidum polysaccharide (GLP), Lycium barbarum polysaccharide (LBP) and yeast glucan (YG)) on primary human NK cells under normal or simulated microgravity (SMG) conditions. Our results demonstrated that polysaccharides markedly promoted the cytotoxicity of NK cells by enhancing IFN-gamma and perforin secretion and increasing the expression of the activating receptor NKp30 under normal conditions. Meanwhile polysaccharides can enhance NK cell function under SMG conditions by restoring the expression of the activating receptor NKG2D and reducing the early apoptosis and late apoptosis/necrosis. Moreover, the antibody neutralization test showed that CR3 may be the critical receptor involved in polysaccharides induced NK cells activation. These findings indicated that polysaccharides may be used as immune regulators to promote the health of the public and astronauts during space missions. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Ting Huyan; Li, Qi; Yang, Hui; Jin, Ming-Liang; Zhang, Ming-Jie; Ye, Lin-Jie; Li, Ji; Huang, Qing-Sheng; Yin, Da-Chuan] Northwestern Polytech Univ, Sch Life Sci, Key Lab Space Biosci & Space Biotechnol, Xian 710072, Shaanxi, Peoples R China. [Ting Huyan; Yin, Da-Chuan] Northwestern Polytech Univ, Sch Mat Sci & Engn, Xian 710072, Shaanxi, Peoples R China. [Zhang, Ming-Jie] US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Yin, DC (reprint author), Northwestern Polytech Univ, Sch Life Sci, 127 Youyi Xilu, Xian 710072, Shaanxi, Peoples R China. EM qingshengh@yahoo.com.cn; yindc@nwpu.edu.cn FU Doctorate Foundation of Northwestern Polytechnical University [CX201023]; National Natural Science Foundation of China (NSFC) [31170816, 30971425] FX We gratefully acknowledge financial support from the Doctorate Foundation of Northwestern Polytechnical University (CX201023), the National Natural Science Foundation of China (NSFC, Grant No. 31170816) and the National Natural Science Foundation of China (NSFC, Grant No. 30971425). NR 45 TC 1 Z9 1 U1 4 U2 26 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0144-8617 EI 1879-1344 J9 CARBOHYD POLYM JI Carbohydr. Polym. PD JAN 30 PY 2014 VL 101 BP 819 EP 827 DI 10.1016/j.carbpol.2013.10.021 PG 9 WC Chemistry, Applied; Chemistry, Organic; Polymer Science SC Chemistry; Polymer Science GA 300WN UT WOS:000330494800103 ER PT J AU Wu, HQ White, M Berendt, R Foringer, RD Khan, M AF Wu, Huiquan White, Maury Berendt, Robert Foringer, Ryan D. Khan, Mansoor TI Integrated Process Analytical Technology Approach for Nucleation Induction Time Measurement and Nucleation Mechanism Assessment for a Dynamic Multicomponent Pharmaceutical Antisolvent Crystallization System SO INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH LA English DT Article ID PRECIPITATION; TEMPERATURE; NAPROXEN; SUPERSATURATION; SPECTROSCOPY; GROWTH; METASTABILITY; PARACETAMOL; MORPHOLOGY; SULFATE AB A comprehensive, real-time PAT process monitoring scheme of using near-infrared (NIR) spectroscopy, focused beam reflectance measurement (FBRM), and particle vision microscopy (PVM) was established for process characterization and process understanding of a model dynamic multicomponent pharmaceutical antisolvent crystallization system. The NIR spectra were subjected to principal component analysis (PCA) to construct the process trajectory; and the final products were characterized by X-ray powder diffraction (XRPD), raman spectrometry, and microscopy. Regardless of the PAT technique (i.e., the NIR-PCA method, the FBRM method, and the PVM method) used, this study shows that the nucleation induction time (t(ind)) increases with temperature. In addition, correlations were observed with R-2 of 0.70-0.98 between PVM method and FBRM method and of 0.58-0.84 between NIR-PCA method and FBRM method. Accounting for the dynamic nature of the experiments and changes in the liquid volume (V) as a function of time, a simplified classical nucleation theory model was derived to reveal the relationship between ln(t(ind)V) and (ln S)(-2) (S is the supersaturation ratio). Regions of very strong and very weak dependence on (ln S)(-2) were identified. Final product characterization and in-process observations of particle morphology at t = t(ind) collectively support that heterogeneous- and homogeneous-nucleation mechanisms are responsible for low S and high S regions, respectively. Therefore, the utility of an integrated-PAT approach for understanding a dynamic multicomponent antisolvent crystallization process and elucidating the nucleation mechanism was demonstrated. C1 [Wu, Huiquan; White, Maury; Berendt, Robert; Foringer, Ryan D.; Khan, Mansoor] US FDA, DPQR, OTR, OPS,CDER, Silver Spring, MD 20993 USA. RP Wu, HQ (reprint author), US FDA, DPQR, OTR, OPS,CDER, HFD 940,Life Sci Bldg 64,FDA White Oak Campus, Silver Spring, MD 20993 USA. EM Huiquan.wu@fda.hhs.gov FU FDA CDER [RSR12-42, RSR13-32] FX We would like to acknowledge Dr. San Kiang at BMS (New Brunswick, NJ), Dr. Vincent L. Vilker (currently retired), and Mr. John Casamento at FDA, Dr. Thomas Wheelock at Iowa State University, Ms. Vaso Vlachos, Mr. Jack Shu, Mr. Ben Smith, and Mr. Paul Scholl at Mettler-Toledo (Columbia, MD), and Mr. Steve Ware and Mr. Brendan Simon from Chemglass Life Science (Vineland, NJ) for their assistances. This work was partially supported by FDA CDER Regulatory Science and Review (RSR) Funding RSR12-42 and RSR13-32. NR 53 TC 7 Z9 7 U1 0 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0888-5885 J9 IND ENG CHEM RES JI Ind. Eng. Chem. Res. PD JAN 29 PY 2014 VL 53 IS 4 BP 1688 EP 1701 DI 10.1021/ie4036466 PG 14 WC Engineering, Chemical SC Engineering GA 302IT UT WOS:000330598800043 ER PT J AU Heckman, CA Weber, J Urban, JM Cayer, ML Boudreau, NS AF Heckman, Carol A. Weber, Jessie Urban, Jason M. Cayer, Marilyn L. Boudreau, Nancy S. TI Protein Kinase C - Its Role in Protrusion Regulation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 58th Annual Meeting of the Biophysical-Society CY FEB 15-19, 2014 CL San Francisco, CA SP Biophys Soc C1 [Heckman, Carol A.; Weber, Jessie; Cayer, Marilyn L.; Boudreau, Nancy S.] Bowling Green State Univ, Bowling Green, OH 43403 USA. [Urban, Jason M.] US FDA, Silver Spring, 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 JAN 28 PY 2014 VL 106 IS 2 SU 1 BP 169A EP 170A PG 2 WC Biophysics SC Biophysics GA AI6QE UT WOS:000337000400840 ER PT J AU Pogribny, IP Rusyn, I AF Pogribny, Igor P. Rusyn, Ivan TI Role of epigenetic aberrations in the development and progression of human hepatocellular carcinoma SO CANCER LETTERS LA English DT Review DE Hepatocellular carcinoma; DNA methylation; Histone modifications; MicroRNAs ID ACTIVE DNA DEMETHYLATION; PERICENTROMERIC SATELLITE REGIONS; ABERRANT PROMOTER METHYLATION; GENOME-WIDE HYPOMETHYLATION; HUMAN HEPATOCARCINOMA CELLS; TUMOR-SUPPRESSOR GENES; HUMAN LIVER-CANCER; MESSENGER-RNA; HEPATITIS-C; METHIONINE ADENOSYLTRANSFERASE AB Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers in humans. The molecular mechanisms leading to the development of HCC are extremely complicated and consist of prominent genetic, genomic, and epigenetic alterations. This review summarizes the current knowledge of the role of epigenetic aberrations, including changes in DNA methylation, histone modifications, and expression of microRNAs in the pathogenesis of HCC. It also emphasizes that identification of the underlying epigenetic alterations that drive cell transformation and promote development and progression of HCC is crucially important for understanding mechanisms of hepatocarcinogenesis, its detection, therapeutic intervention, and prevention. Published by Elsevier Ireland Ltd. C1 [Pogribny, Igor P.] NCTR, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. RP Pogribny, IP (reprint author), NCTR, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov; iir@unc.edu RI Rusyn, Ivan/S-2426-2016 FU NIH [R01 ES015241, P42 ES005948] FX This work was supported, in part, by Grants from NIH (R01 ES015241 and P42 ES005948). NR 174 TC 51 Z9 57 U1 3 U2 45 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 EI 1872-7980 J9 CANCER LETT JI Cancer Lett. PD JAN 28 PY 2014 VL 342 IS 2 SI SI BP 223 EP 230 DI 10.1016/j.canlet.2012.01.038 PG 8 WC Oncology SC Oncology GA 278ZJ UT WOS:000328928100008 PM 22306342 ER PT J AU Cole, C Krampis, K Karagiannis, K Almeida, JS Faison, WJ Motwani, M Wan, Q Golikov, A Pan, Y Simonyan, V Mazumder, R AF Cole, Charles Krampis, Konstantinos Karagiannis, Konstantinos Almeida, Jonas S. Faison, William J. Motwani, Mona Wan, Quan Golikov, Anton Pan, Yang Simonyan, Vahan Mazumder, Raja TI Non-synonymous variations in cancer and their effects on the human proteome: workflow for NGS data biocuration and proteome-wide analysis of TCGA data SO BMC BIOINFORMATICS LA English DT Article DE SRA; TCGA; nsSNV; SNV; SNP; Next-gen; NGS; Phylogenetics; Cancer ID CONVERTING-ENZYME GENE; RHO-FAMILY GTPASES; BREAST-CANCER; HUMAN GENOME; CLASSIFICATION-SYSTEM; SEQUENCING DATA; CELL-CELL; INFORMATION; MUTATIONS; RESOURCE AB Background: Next-generation sequencing (NGS) technologies have resulted in petabytes of scattered data, decentralized in archives, databases and sometimes in isolated hard-disks which are inaccessible for browsing and analysis. It is expected that curated secondary databases will help organize some of this Big Data thereby allowing users better navigate, search and compute on it. Results: To address the above challenge, we have implemented a NGS biocuration workflow and are analyzing short read sequences and associated metadata from cancer patients to better understand the human variome. Curation of variation and other related information from control (normal tissue) and case (tumor) samples will provide comprehensive background information that can be used in genomic medicine research and application studies. Our approach includes a CloudBioLinux Virtual Machine which is used upstream of an integrated High-performance Integrated Virtual Environment (HIVE) that encapsulates Curated Short Read archive (CSR) and a proteome-wide variation effect analysis tool (SNVDis). As a proof-of-concept, we have curated and analyzed control and case breast cancer datasets from the NCI cancer genomics program - The Cancer Genome Atlas (TCGA). Our efforts include reviewing and recording in CSR available clinical information on patients, mapping of the reads to the reference followed by identification of non-synonymous Single Nucleotide Variations (nsSNVs) and integrating the data with tools that allow analysis of effect nsSNVs on the human proteome. Furthermore, we have also developed a novel phylogenetic analysis algorithm that uses SNV positions and can be used to classify the patient population. The workflow described here lays the foundation for analysis of short read sequence data to identify rare and novel SNVs that are not present in dbSNP and therefore provides a more comprehensive understanding of the human variome. Variation results for single genes as well as the entire study are available from the CSR website (http://hive.biochemistry.gwu.edu/dna.cgi?cmd=csr). Conclusions: Availability of thousands of sequenced samples from patients provides a rich repository of sequence information that can be utilized to identify individual level SNVs and their effect on the human proteome beyond what the dbSNP database provides. C1 [Cole, Charles; Karagiannis, Konstantinos; Faison, William J.; Motwani, Mona; Wan, Quan; Pan, Yang; Mazumder, Raja] George Washington Univ, Med Ctr, Dept Biochem & Mol Med, Washington, DC 20037 USA. [Krampis, Konstantinos] J Craig Venter Inst, Rockville, MD 20850 USA. [Almeida, Jonas S.] Univ Alabama Birmingham, Dept Pathol, Div Informat, Birmingham, AL 35294 USA. [Golikov, Anton; Simonyan, Vahan] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Mazumder, Raja] George Washington Univ, McCormick Genom & Prote Ctr, Washington, DC 20037 USA. RP Mazumder, R (reprint author), George Washington Univ, Med Ctr, Dept Biochem & Mol Med, Washington, DC 20037 USA. EM mazumder@gwu.edu OI Wan, Quan/0000-0003-4289-3487; Pan, Yang/0000-0003-3487-7233 FU Research Participation Program at the Center for Biologics Evaluation [U01 CA168926] FX We want to thank P Satti and JH Yu for help with database and interface development. We thank the TCGA tumor-specific groups for providing the data. We also thank Robert Foreman and Garrett Fields for providing HIVE system support. All computations were performed at High-performance Integrated Virtual Environment (HIVE) located at The George Washington University and implemented/co-developed by Drs. Raja Mazumder and Vahan Simonyan. This project is supported in part by U01 CA168926 and Research Participation Program at the Center for Biologics 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 88 TC 7 Z9 7 U1 2 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JAN 27 PY 2014 VL 15 AR 28 DI 10.1186/1471-2105-15-28 PG 18 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA AF1GY UT WOS:000334463600001 PM 24467687 ER PT J AU Yang, AX Chong, NJ Jiang, YF Catalano, J Puri, RK Khleif, SN AF Yang, Amy X. Chong, Numju Jiang, Yufei Catalano, Jennifer Puri, Raj K. Khleif, Samir N. TI Molecular Characterization of Antigen-Peptide Pulsed Dendritic Cells: Immature Dendritic Cells Develop a Distinct Molecular Profile when Pulsed with Antigen Peptide SO PLOS ONE LA English DT Article ID NECROSIS-FACTOR-ALPHA; OLIGONUCLEOTIDE MICROARRAYS; INTERFERON-GAMMA; GENE-EXPRESSION; CERVICAL-CANCER; TUMOR-ANTIGEN; IN-VITRO; MATURATION; INDUCTION; IMMUNITY AB As dendritic cells (DCs) are the most potent professional antigen-presenting cells, they are being tested as cancer vaccines for immunotherapy of established cancers. Although numerous studies have characterized DCs by their phenotype and function, few have identified potential molecular markers of antigen presentation prior to vaccination of host. In this study we generated pre-immature DC (piDC), immature DC (iDC), and mature DC (mDC) from human peripheral blood monocytes (PBMC) obtained from HLA-A2 healthy donors, and pulsed them with human papillomavirus E7 peptide (p11-20), a class I HLA-A2 binding antigen. We then characterized DCs for cell surface phenotype and gene expression profile by microarray technology. We identified a set of 59 genes that distinguished three differentiation stages of DCs (piDC, iDC and mDC). When piDC, iDC and mDC were pulsed with E7 peptide for 2 hrs, the surface phenotype did not change, however, iDCs rather than mDCs showed transcriptional response by up-regulation of a set of genes. A total of 52 genes were modulated in iDC upon antigen pulsing. Elongation of pulse time for iDCs to 10 and 24 hrs did not significantly bring further changes in gene expression. The E7 peptide up-modulated immune response (KPNA7, IGSF6, NCR3, TREM2, TUBAL3, IL8, NFKBIA), pro-apoptosis (BTG1, SEMA6A, IGFBP3 and SRGN), anti-apoptosis (NFKBIA), DNA repair (MRPS11, RAD21, TXNRD1), and cell adhesion and cell migration genes (EPHA1, PGF, IL8 and CYR61) in iDCs. We confirmed our results by Q-PCR analysis. The E7 peptide but not control peptide (PADRE) induced up-regulation of NFKB1A gene only in HLA-A2 positive iDCs and not in HLA-A2 negative iDCs. These results suggest that E7 up-regulation of genes is specific and HLA restricted and that these genes may represent markers of antigen presentation and help rapidly assess the quality of dendritic cells prior to administration to the host. C1 [Yang, Amy X.; Catalano, Jennifer; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Chong, Numju; Jiang, Yufei; Khleif, Samir N.] NCI, Vaccine Branch, Bethesda, MD 20892 USA. [Khleif, Samir N.] Georgia Regent Univ, Ctr Canc, Augusta, GA USA. RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM raj.puri@fda.hhs.gov NR 26 TC 2 Z9 2 U1 1 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 2014 VL 9 IS 1 AR e86306 DI 10.1371/journal.pone.0086306 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 301BI UT WOS:000330507300052 PM 24475103 ER PT J AU Song, FH Monroe, D El-Demerdash, A Palmer, C AF Song, Fenhong Monroe, Douglas El-Demerdash, Aref Palmer, Cynthia TI Screening for multiple weight loss and related drugs in dietary supplement materials by flow injection tandem mass spectrometry and their confirmation by liquid chromatography tandem mass spectrometry SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Weight loss drugs; Dietary supplement; Sibutramine; Flow injection; LC-MS/MS ID SLIMMING FUNCTIONAL FOODS; SIBUTRAMINE; MS; ADULTERANTS; DESMETHYLSIBUTRAMINE; TADALAFIL; ANALOGS; HEALTH AB A new method has been developed using flow injection tandem mass spectrometry to semi-quantitatively screen for weight loss drugs, including sibutramine, N-desmethylsibutramine, N-didesmethylsibutramine, and phenolphthalein in dietary supplements. Positive identification of these drugs in samples was further confirmed and quantified by liquid chromatography tandem mass spectrometry. The degradation products of sibutramine were observed and identified by LC-MS/MS which include N-desmethylsibutramine, N-didesmethylsibutramine, N-formyldesmethylsibutramine, and N-formyldidesmethylsibutramine. Published by Elsevier B.V. C1 [Song, Fenhong; Monroe, Douglas; El-Demerdash, Aref] US FDA, Method Dev & Total Diet Res Ctr, Lenexa, KS 66214 USA. [Palmer, Cynthia] US FDA, Philadelphia Lab, Philadelphia, PA 19106 USA. RP Song, FH (reprint author), US FDA, Method Dev & Total Diet Res Ctr, 11630 W 80th St, Lenexa, KS 66214 USA. EM fenhong.song@fda.hhs.gov NR 20 TC 15 Z9 16 U1 1 U2 26 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 2014 VL 88 BP 136 EP 143 DI 10.1016/j.jpba.2013.08.031 PG 8 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 287HN UT WOS:000329532800019 PM 24055849 ER PT J AU Avula, B Wang, YH Wang, M Avonto, C Zhao, JP Smillie, TJ Rua, DG Khan, IA AF Avula, Bharathi Wang, Yan-Hong Wang, Mei Avonto, Cristina Zhao, Jianping Smillie, Troy J. Rua, Diego Khan, Ikhlas A. TI Quantitative determination of phenolic compounds by UHPLC-UV-MS and use of partial least-square discriminant analysis to differentiate chemo-types of Chamomile/Chrysanthemum flower heads SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Chamomiles; Chrysanthemum morifolium; Asteraceae; UHPLC-UV-QTOF/MS; Phenolic compounds ID CHRYSANTHEMUM-MORIFOLIUM EXTRACT; RECUTITA L. RAUSCHERT; MATRICARIA-CHAMOMILLA; CHAMAEMELUM-NOBILE; APIGENIN; ACIDS; HPLC; IDENTIFICATION; DERIVATIVES; COUMARINS AB A new rapid UHPLC-UV-QTOF/MS method has been developed for the simultaneous analysis of nine phenolic compounds [(Z)-2-beta-D-glucopyranosyloxy-4-methoxycinnamic acid (cis-GMCA), chlorogenic acid, (E)-2-beta-D-glucopyranosyloxy-4-methoxycinnamic acid (trans-GMCA), quercetagetin-7-O-beta-D-glucopyranoside, luteolin-7-O-beta-D-glucoside, apigenin-7-O-beta-D-glucoside, chamaemeloside, apigenin 7-O-(6 ''-O-acetyl-beta-D-glucopyranoside), apigenin] and one polyacetylene (tonghaosu) from the flower heads of Chamomile/Chrysanthemum samples. The chromatographic separation was achieved using a reversed phase C-18 column with a mobile phase of water and acetonitrile, both containing 0.05% formic acid. The ten compounds were completely separated within 15 min at a flow rate of 0.25 mL/min with a 2 mu L injection volume. The different chemo-types of Chamomiles/Chrysanthemum displayed variations in the presence of chemical constituents. German Chamomile samples confirmed the presence of cis-GMCA, trans-GMCA, apigenin-7-O-beta-D-glucoside and tonghaosu as major constituents whereas Roman chamomile samples confirmed the presence of chamamaeloside and apigenin as major compounds. The Chrysanthemum monfolium samples showed the presence of luteolin-7-O-beta-D-glucose as the major compound. The method was applied for the analysis of various commercial products including capsules, tea bags, body and hair care products. LC-mass spectrometry with electrospray ionization (ESI) interface method is described for the evaluation of ten compounds in plant samples and commercial products. This method involved the detection of [M+Na](+) and [M+H](+) ions in the positive mode. Partial least squares discriminant analysis (PLS-DA) was used to visualize commercial samples quality and may be of value for discriminating between chamomile types and Chrysanthemum with regards to the relative content of individual constituents. The results indicated that the method is suitable as a quality control test for various Chamomile/Chrysanthemum samples and market products. (C) 2013 Elsevier B.V. All rights reserved. C1 [Avula, Bharathi; Wang, Yan-Hong; Wang, Mei; Avonto, Cristina; Zhao, Jianping; Smillie, Troy J.; Khan, Ikhlas A.] Univ Mississippi, Pharmaceut Sci Res Inst, Natl Ctr Nat Prod Res, University, MS 38677 USA. [Khan, Ikhlas A.] Univ Mississippi, Sch Pharm, Dept Pharmacognosy, University, MS 38677 USA. [Rua, Diego] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Avula, B (reprint author), Univ Mississippi, Pharmaceut Sci Res Inst, Natl Ctr Nat Prod Res, University, MS 38677 USA. EM bavula@olemiss.edu; ikhan@olemiss.edu OI Avonto, Cristina/0000-0002-8209-6813 FU Science Based Authentication of Dietary Supplements; Food and Drug Administration [5U01FD004246]; United States Department of Agriculture, Agricultural Research Service [58-6408-02-1-612] FX This research is supported in part by "Science Based Authentication of Dietary Supplements" funded by the Food and Drug Administration Grant Number 5U01FD004246, the United States Department of Agriculture, Agricultural Research Service, Specific Cooperative Agreement No. 58-6408-02-1-612, and the authors would like to thank Annette Ford for the extractions of plant samples. The authors also would like to thank Dr. Feng Wei for collecting Chrysanthemum samples. NR 30 TC 21 Z9 23 U1 5 U2 94 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 2014 VL 88 BP 278 EP 288 DI 10.1016/j.jpba.2013.08.037 PG 11 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 287HN UT WOS:000329532800038 PM 24095803 ER PT J AU Pawar, RS Grundel, E Fardin-Kia, AR Rader, JI AF Pawar, Rahul S. Grundel, Erich Fardin-Kia, Ali Reza Rader, Jeanne I. TI Determination of selected biogenic amines in Acacia rigidula plant materials and dietary supplements using LC-MS/MS methods SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Acacia rigidula; Biogenic amines; Dietary supplement; beta-Methylphenethylamine; Amphetamine ID LABELED INTERNAL STANDARD; MASS-SPECTROMETRY; TOXIC AMINES; ALKALOIDS; PHENYLETHYLAMINE; AMPHETAMINE; BERLANDIERI; ISOMERS; IDENTIFICATION; DERIVATIVES AB Extracts of Acacia rigidula leaves are used in weight-loss products sold in vitamin shops and over the internet with little or no published data about their potential biological effects. In our chemical investigations on authenticated A. rigidula plant material, we established a rapid and sensitive LC-MS/MS method for the quantitative determination of several phenethylamine, tyramine and tryptamine derivatives. Stable isotopically labeled compounds were used as internal standards for quantitative analysis. We found total calculated contents of 6 biogenic amines in A. rigidula leaf of 18.6 and 32.9 mu g/g. The content of selected amines in 21 dietary supplements labeled as containing A. rigidula was determined by a second LC-MS/MS method. Our study revealed significant differences in the amine profiles of authenticated plant materials and dietary supplements. beta-Methylphenethylamine, a non-natural compound, was found in 9 of the 21 dietary supplement products. p-Methylphenethylamine was found at levels of 960-60,500 mu g/g while phenethylamine was found at levels of 710-171,620 mu g/g. beta-methylphenethylamine is a positional isomer of amphetamine and our results showed that it can be misidentified as amphetamine during LC-MS analysis. An independent GC-MS analysis was used to confirm the presence of beta-methylphenethylamine and the absence of amphetamine in dietary supplements labeled as containing A. rigidula. This study demonstrates that confirmations by independent analytical methods are essential to verify findings of unusual or unexpected compounds in dietary supplements. Published by Elsevier B.V. C1 [Pawar, Rahul S.; Grundel, Erich; Fardin-Kia, Ali Reza; Rader, Jeanne I.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Pawar, RS (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Rahul.Pawar@fda.hhs.gov NR 28 TC 20 Z9 20 U1 5 U2 38 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 2014 VL 88 BP 457 EP 466 DI 10.1016/j.jpba.2013.09.012 PG 10 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 287HN UT WOS:000329532800060 PM 24176750 ER PT J AU Sacks, LV Shamsuddin, HH Yasinskaya, YI Bouri, K Lanthier, ML Sherman, RE AF Sacks, Leonard V. Shamsuddin, Hala H. Yasinskaya, Yuliya I. Bouri, Khaled Lanthier, Michael L. Sherman, Rachel E. TI Scientific and Regulatory Reasons for Delay and Denial of FDA Approval of Initial Applications for New Drugs, 2000-2012 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SURROGATE END-POINTS; CLINICAL-TRIALS; PHASE-III; DISEASE; CANCER; RATES AB IMPORTANCE Some new drug applications fail because of inadequate drug performance and others are not approved because the information submitted to the US Food and Drug Administration (FDA) is unsatisfactory to make that determination. Resubmission of failed applications is costly, delaying marketing approval and the availability of new drugs to patients. OBJECTIVE To identify the reasons that FDA marketing approval for new drugs was delayed or denied. DESIGN, SETTING, AND PARTICIPANTS A retrospective review of FDA documents and extraction of data were performed. We examined all drug applications first submitted to the FDA between 2000 and 2012 for new molecular entities (NMEs), which are active ingredients never before marketed in the United States in any form. Using FDA correspondence and reviews, we investigated the reasons NMEs failed to obtain FDA approval. MAIN OUTCOMES AND MEASURES Reasons for delayed FDA approval or nonapproval of NME applications. RESULTS Of the 302 identified NME applications, 151 (50%) were approved when first submitted and 222 (73.5%) were ultimately approved. Seventy-one applications required 1 or more resubmissions before approval, with a median delay to approval of 435 days following the first unsuccessful submission. Of the unsuccessful first-time applications, 24 (15.9%) included uncertainties related to dose selection, 20 (13.2%) choice of study end points that failed to adequately reflect a clinically meaningful effect, 20 (13.2%) inconsistent results when different end points were tested, 17 (11.3%) inconsistent results when different trials or study sites were compared, and 20 (13.2%) poor efficacy when compared with the standard of care. The frequency of safety deficiencies was similar among never-approved drugs compared with those with delayed approval (43 of 80 never approved [53.8%] vs 37 of 71 eventually approved [52.1%]; difference, 1.7% [95% CI, -14.86% to 18.05%]; P = .87). However, efficacy deficiencies were significantly more frequent among the never-approved drugs than among those with delayed approvals (61 of 80 never approved [76.3%] vs 28 of 71 eventually approved [39.4%]; difference, 36.9% [95% CI, 20.25% to 50.86%]; P < .001). CONCLUSIONS AND RELEVANCE Several potentially preventable deficiencies, including failure to select optimal drug doses and suitable study end points, accounted for significant delays in the approval of new drugs. Understanding the reasons for previous failures is helpful to improve the efficiency of clinical development for new drugs. C1 [Sacks, Leonard V.; Sherman, Rachel E.] US FDA, Off Med Policy, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Shamsuddin, Hala H.; Yasinskaya, Yuliya I.] US FDA, Off Antimicrobial Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Bouri, Khaled] US FDA, Off Crit Path Programs, Off Commissioner, Silver Spring, MD 20993 USA. [Lanthier, Michael L.] US FDA, Off Commissioner, Silver Spring, MD 20993 USA. RP Sacks, LV (reprint author), US FDA, Off Med Policy, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Room 6342, Silver Spring, MD 20993 USA. EM leonard.sacks@fda.hhs.gov NR 25 TC 30 Z9 30 U1 2 U2 17 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 22 PY 2014 VL 311 IS 4 BP 378 EP 384 DI 10.1001/jama.2013.282542 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 292YT UT WOS:000329939300023 PM 24449316 ER PT J AU Qu, FL Zhang, Y Rasooly, A Yang, MH AF Qu, Fengli Zhang, Yi Rasooly, Avraham Yang, Minghui TI Electrochemical Biosensing Platform Using Hydrogel Prepared from Ferrocene Modified Amino Acid as Highly Efficient Immobilization Matrix SO ANALYTICAL CHEMISTRY LA English DT Article ID GLUCOSE-OXIDASE; AMPEROMETRIC DETERMINATION; ELECTRODE; HYBRID; LAYER; CONSTRUCTION; PERFORMANCE; FABRICATION; MULTILAYER; MONOLAYER AB To increase the loading of glucose oxidase (GOx) and simplify glucose biosensor fabrication, hydrogel prepared from ferrocene (Fc) modified amino acid phenylalanine (Phe, F) was utilized for the incorporation of GOx. The synthesized hydrogel displays good biocompatibility and contains a significant number of Fc moieties, which can be considered as an ideal matrix to immobilize enzymes for the preparation of mediator-based biosensors. The hydrogel was studied by scanning electron microscopy, which indicated that it was composed of nanofibers with a diameter of around 50-100 nm and length extended to 1 mm. With the addition of GOx into the hydrogel and by directly dropping the resulting biocomposite onto the electrode surface, a glucose biosensor, that displays good performance due to improved enzyme loading and efficient electron transfer, can be simply constructed. The favorable network structure and good biocompatibility of the hydrogel could effectively avoid enzyme leakage and maintain the bioactivity of the enzymes, which resulted in good stability of the biosensor. The biosensor was utilized for the detection of glucose in blood samples with results comparable to those obtained from the hospital. The hydrogel as a functional component of an amperometric biosensor has implications for future development of biosensors and for clinical applications. C1 [Qu, Fengli; Zhang, Yi; Yang, Minghui] Cent S Univ, Coll Chem & Chem Engn, Minist Educ, Key Lab Resources Chem Nonferrous Met, Changsha 410083, Hunan, Peoples R China. [Qu, Fengli] Qufu Normal Univ, Coll Chem & Chem Engn, Qufu 273165, Shandong, Peoples R China. [Rasooly, Avraham] FDA, Off Sci & Engn, Div Biol, Silver Spring, MD 20993 USA. RP Yang, MH (reprint author), Cent S Univ, Coll Chem & Chem Engn, Minist Educ, Key Lab Resources Chem Nonferrous Met, Changsha 410083, Hunan, Peoples R China. EM yangminghui@csu.edu.cn FU National Natural Science Foundation of China [21105128, 21375076, 20973201, 91127024]; National Key Basic Research Program of China [2014CB744502] FX We are grateful for the support of the National Natural Science Foundation of China (21105128, 21375076, 20973201, and 91127024) and the National Key Basic Research Program of China (2014CB744502). The authors acknowledge Dr. Rodney Priestley from Princeton University for editorial assistance. NR 38 TC 32 Z9 32 U1 9 U2 100 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 EI 1520-6882 J9 ANAL CHEM JI Anal. Chem. PD JAN 21 PY 2014 VL 86 IS 2 BP 973 EP 976 DI 10.1021/ac403478z PG 4 WC Chemistry, Analytical SC Chemistry GA 296SA UT WOS:000330204500002 PM 24383679 ER PT J AU Walker, BN James, RH Calogero, D Ilev, IK AF Walker, Bennett N. James, Robert H. Calogero, Don Ilev, Ilko K. TI Impact of environmental temperature on optical power properties of intraocular lenses SO APPLIED OPTICS LA English DT Article AB Optical power properties of lenses and materials in general can be influenced by thermal changes of the material and surrounding medium. In the case of an intraocular lens (IOL) implant, the spherical power (SP), cylinder power, (CP), astigmatism, and spherical aberration are the critical fundamental properties that can significantly impact its efficacy. Directly evaluating how changes in temperature can affect these optical properties may show the importance of considering temperature when evaluating IOL optical characteristics. In this paper, we present a quantitative study on evaluating the impact of environmental temperature changes on IOL fundamental optical properties by testing IOL samples with different materials (e.g., hydrophobic and hydrophilic) and designs (e.g., monofocal and toric) to better encompass types of IOLs in conventional use today. The results from this study demonstrate that significant changes are observed as temperatures are changed from room temperature (20 degrees C) to slightly above body temperature (40 degrees C). Findings indicate that evaluating optical properties at arbitrary temperatures could significantly affect the characterization of IOLs that are already near the tolerance thresholds. (C) 2014 Optical Society of America C1 [Walker, Bennett N.; James, Robert H.; Ilev, Ilko K.] US FDA, Opt Therapeut & Med Nanophoton Lab, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. [Calogero, Don] US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Walker, BN (reprint author), US FDA, Opt Therapeut & Med Nanophoton Lab, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. EM bennett.walker@fda.hhs.gov OI WALKER, BENNETT/0000-0003-0221-1904 FU Oak Ridge Institute for Science and Education (ORISE) FX The authors wish to thank Lumetrics Incorporation for all of their support with the commercial aberrometer. This work was also supported by Oak Ridge Institute for Science and Education (ORISE). In addition, the laboratory assistance from students Aurin Chakravarty and Samuel Song significantly helped facilitate the project. 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 8 TC 4 Z9 4 U1 0 U2 6 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD JAN 20 PY 2014 VL 53 IS 3 BP 453 EP 457 DI 10.1364/AO.53.000453 PG 5 WC Optics SC Optics GA 296GD UT WOS:000330172300019 PM 24514132 ER PT J AU Weng, ZQ Zhou, P Salminen, WF Yang, X Harrill, AH Cao, ZJ Mattes, WB Mendrick, DL Shi, Q AF Weng, Zuquan Zhou, Peng Salminen, William F. Yang, Xi Harrill, Alison H. Cao, Zhijun Mattes, William B. Mendrick, Donna L. Shi, Qiang TI Green tea epigallocatechin gallate binds to and inhibits respiratory complexes in swelling but not normal rat hepatic mitochondria SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Green tea; Epigallocatechin gallate; Mitochondria; Respiratory chain complexes; Rat; Liver ID PERMEABILITY TRANSITION PORE; INDUCED LIVER-INJURY; CELL-DEATH; ACETAMINOPHEN HEPATOTOXICITY; POLYPHENON-E; MECHANISMS; MOUSE; HEPATOCYTES; APOPTOSIS; CATECHINS AB Epigallocatechin gallate (EGCG), the major flavonoid in green tea, is consumed via tea products and dietary supplements, and has been tested in clinical trials. However, EGCG can cause hepatotoxicity in humans and animals by unknown mechanisms. Here EGCG effects on rat liver mitochondria were examined. EGCG showed negligible effects on oxidative phosphorylation at 7.5-100 mu M in normal mitochondria. However, respiratory chain complexes (RCCs) were profoundly inhibited by EGCG in mitochondria undergoing Ca2+ overload-induced mitochondrial permeability transition (MPT). As RCCs are located in mitochondrial inner membranes (IM) and matrix, it was reasoned that EGCG could not readily pass through IM to affect RCCs in normal mitochondria but may do so when IM integrity is compromised. This speculation was substantiated in three ways. (1) Purified EGCG-bound proteins were barely detectable in normal mitochondria and contained no RCCs as determined by Western blotting, but swelling mitochondria contained about 1.5-fold more EGCG-bound proteins which included four RCC subunits together with cyclophilin D that locates in mitochondrial matrix. (2) Swelling mitochondria consumed more EGCG than normal ones. (3) The MPT blocker cyclosporine A diminished the above-mentioned difference. Among four subunits of RCC II, only SDHA and SDHB which locate in mitochondrial matrix, but not SDHC or SDHD which insert into the IM, were found to be EGCG targets. Interestingly, EGCG promoted Ca2+ overload-induced MPT only when moderate MPT already commenced. This study identified hepatic RCCs as targets for EGCG in swelling but not normal mitochondria, suggesting EGCG may trigger hepatotoxicity by worsening pre-existing mitochondria abnormalities. Published by Elsevier Inc. C1 [Weng, Zuquan; Zhou, Peng; Salminen, William F.; Yang, Xi; Cao, Zhijun; Mendrick, Donna L.; Shi, Qiang] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Harrill, Alison H.] Univ Arkansas Med Sci, Dept Occupat & Environm Hlth, Little Rock, AR 72205 USA. [Mattes, William B.] PharmPoint Consulting, Poolesville, MD 20837 USA. RP Shi, Q (reprint author), US FDA, Div Syst Biol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Qiang.Shi@fda.hhs.gov FU National Center for Toxicological Research FX Drs. Zuquan Weng and Peng Zhou are supported by the Research Participation Program at the National Center for Toxicological Research administrated 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. Dr. William Mattes is a contractor with the FDA NCTR. NR 29 TC 7 Z9 7 U1 0 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 17 PY 2014 VL 443 IS 3 BP 1097 EP 1104 DI 10.1016/j.bbrc.2013.12.110 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AA9LM UT WOS:000331415000052 PM 24384371 ER PT J AU Gu, Q Yu, LR AF Gu, Qiang Yu, Li-Rong TI Proteomics quality and standard: From a regulatory perspective SO JOURNAL OF PROTEOMICS LA English DT Review DE Proteomics; Mass spectrometry; Quality control; Standards; Biomarker qualification; Regulatory decision ID TANDEM MASS-SPECTROMETRY; COMPLEX PROTEIN MIXTURES; QUANTITATIVE PROTEOMICS; MINIMUM INFORMATION; GEL-ELECTROPHORESIS; GUIDELINES; QUANTIFICATION; CHROMATOGRAPHY; PERFORMANCE; REAGENTS AB Proteomics has emerged as a rapidly expanding field dealing with large-scale protein analyses. It is anticipated that proteomics data will be increasingly submitted to the U.S. Food and Drug Administration (FDA) for biomarker qualification or in conjunction with applications for the approval of drugs, medical devices, and other FDA-regulated consumer products. To date, however, no established guideline has been available regarding the generation, submission and assessment of the quality of proteomics data that will be reviewed by regulatory agencies for decision making. Therefore, this commentary is aimed at provoking some thoughts and debates towards developing a framework which can guide future proteomics data submission. The ultimate goal is to establish quality control standards for proteomics data generation and evaluation, and to prepare government agencies such as the FDA to meet future obligations utilizing proteomics data to support regulatory decision. Published by Elsevier B.V. C1 [Gu, Qiang; Yu, Li-Rong] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Yu, LR (reprint author), US FDA, Biomarkers & Alternat Models Branch, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM Lirong.Yu@fda.hhs.gov FU FDA Commissioner's Fellowship Program FX The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral. proteomexchange.org) via the PRIDE partner repository [53] with the dataset identifier PXDO00334. This work was supported in part by FDA Commissioner's Fellowship Program and by an appointment to the Reiearch Participation 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. We wish to thank Yuan Gao, Ricky Holland, Xiaoqing Guo, Nan Mei, Reagan Kelly, Joshua Xu, and Hong Fang for providing various levels of help and assistance throughout this study. The views expressed here are those of the authors and not necessarily of the U.S. Food and Drug Administration, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 52 TC 5 Z9 5 U1 2 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-3919 EI 1876-7737 J9 J PROTEOMICS JI J. Proteomics PD JAN 16 PY 2014 VL 96 BP 353 EP 359 DI 10.1016/j.jprot.2013.11.024 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA AB6RD UT WOS:000331916300028 PM 24316359 ER PT J AU Belcher, JD Chen, CS Nguyen, J Milbauer, LM Abdulla, F Alayash, AI Smith, A Nath, KA Hebbel, RP Vercellotti, GM AF Belcher, John D. Chen, Chunsheng Julia Nguyen Milbauer, Liming Abdulla, Fuad Alayash, Abdu I. Smith, Ann Nath, Karl A. Hebbel, Robert P. Vercellotti, Gregory M. TI Heme triggers TLR4 signaling leading to endothelial cell activation and vaso-occlusion in murine sickle cell disease SO BLOOD LA English DT Article ID OXYGEN SPECIES GENERATION; TRANSGENIC MICE; P-SELECTIN; HEMOLYTIC DISEASES; VASCULAR OCCLUSION; NITRIC-OXIDE; KAPPA-B; HEMOGLOBIN; HEMOPEXIN; RECEPTOR AB Treatment of sickle cell disease (SCD) is hampered by incomplete understanding of pathways linking hemolysis to vaso-occlusion. We investigated these pathways in transgenic sickle mice. Infusion of hemoglobin or heme triggered vaso-occlusion in sickle, but not normal, mice. Methemoglobin, but not heme-stabilized cyanomethemoglobin, induced vaso-occlusion, indicating heme liberation is necessary. In corroboration, hemoglobin-induced vaso-occlusion was blocked by the methemoglobin reducing agent methylene blue, haptoglobin, or the heme-binding protein hemopexin. Untreated HbSS mice, but not HbAA mice, exhibited similar to 10% vaso-occlusion in steady state that was inhibited by haptoglobin or hemopexin infusion. Antibody blockade of adhesion molecules P-selectin, von Willebrand factor (VWF), E-selectin, vascular cell adhesion molecule 1, intercellular adhesion molecule 1, platelet endothelial cell (EC) adhesion molecule 1, alpha 4 beta 1, or alpha V beta 3 integrin prevented vaso-occlusion. Heme rapidly (5 minutes) mobilized Weibel-Palade body (WPB) P-selectin and VWF onto EC and vessel wall surfaces and activated EC nuclear factor kappa B (NF-kappa B). This was mediated by TLR4 as TAK-242 blocked WPB degranulation, NF-kappa B activation, vaso-occlusion, leukocyte rolling/adhesion, and heme lethality. TLR4(-/-) mice transplanted with TLR4(+/+) sickle bone marrow exhibited no heme-induced vaso-occlusion. The TLR4 agonist lipopolysaccharide (LPS) activated ECs and triggered vaso-occlusion that was inhibited by TAK-242, linking hemolysis-and infection-induced vaso-occlusive crises to TLR4 signaling. Heme and LPS failed to activate VWF and NF-kappa B in TLR4(-/-) ECs. Anti-LPS immunoglobulin G blocked LPS-induced, but not heme-induced, vaso-occlusion, illustrating LPS-independent TLR4 signaling by heme. Inhibition of protein kinase C, NADPH oxidase, or antioxidant treatment blocked heme-mediated stasis, WPB degranulation, and oxidant production. We conclude that intravascular hemolysis in SCD releases heme that activates endothelial TLR4 signaling leading to WPB degranulation, NF-kappa B activation, and vaso-occlusion. C1 [Belcher, John D.; Chen, Chunsheng; Julia Nguyen; Milbauer, Liming; Abdulla, Fuad; Hebbel, Robert P.; Vercellotti, Gregory M.] Univ Minnesota, Vasc Biol Ctr, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. [Alayash, Abdu I.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Smith, Ann] Univ Missouri, Div Mol Biol & Biochem, Sch Biol Sci, Kansas City, MO 64110 USA. [Nath, Karl A.] Mayo Clin Fdn, Nephrol Res Unit, Rochester, MN USA. RP Belcher, JD (reprint author), Univ Minnesota, 420 Delaware St SE,MMC 480, Minneapolis, MN 55455 USA. EM belcher@umn.edu RI Abdulla, Fuad/A-3337-2015 FU National Institutes of Health, National Heart, Lung, and Blood Institute [P01HL55552, HL115467-01, HL1109000-01A1]; Sangart; University of Missouri Research Board; School of Biological Sciences at University of Missouri-Kansas City Research Incentive Funds; National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [DK47060] FX This work was supported by grants from the National Institutes of Health, National Heart, Lung, and Blood Institute This work was supported by grants from the National Institutes of Health, National Heart, Lung, and Blood Institute (P01HL55552; R.P.H. and G.M.V.), (HL115467-01; G.M.V. and J.D.B.), (HL1109000-01A1; A.I.A.), and by a research grant award from Sangart (G.M.V. and J.D.B.). Dr Ann Smith thanks the University of Missouri Research Board and School of Biological Sciences at University of Missouri-Kansas City Research Incentive Funds for support. K.A.N. received support from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (DK47060). We would like to thank Graham Brown for preparation of metHb and cyanometHb, Dr Heather Bechtel for assistance with the graphics in Figure 7, Dr Mark Young and Ashok Malavalli at Sangart for the preparation and generous gift of stroma-free Hb, Bio Products Laboratory for the preparation and generous donation of human haptoglobin, and Bo Hedlund for the generous gift of S-DFO. Michael J. Franklin read the manuscript and was extremely helpful in making editorial suggestions. NR 55 TC 100 Z9 101 U1 4 U2 13 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 16 PY 2014 VL 123 IS 3 BP 377 EP 390 DI 10.1182/blood-2013-04-495887 PG 14 WC Hematology SC Hematology GA 290IP UT WOS:000329748700017 PM 24277079 ER PT J AU He, WW Kim, HK Warner, WG Melka, D Callahan, JH Yin, JJ AF He, Weiwei Kim, Hyun-Kyung Warner, Wayne G. Melka, David Callahan, John H. Yin, Jun-Jie TI Photogenerated Charge Carriers and Reactive Oxygen Species in ZnO/Au Hybrid Nanostructures with Enhanced Photocatalytic and Antibacterial Activity SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ELECTRON-SPIN RESONANCE; AU NANOPARTICLES; TIO2; SEMICONDUCTOR; TITANIUM; GOLD; DECOMPOSITION; SPECTROSCOPY; CHEMISTRY; MECHANISM AB Semiconductor nanostructures with photocatalytic activity have the potential for many applications including remediation of environmental pollutants and use in antibacterial products. An effective way for promoting photocatalytic activity is depositing noble metal nanoparticles (NPs) on a semiconductor. In this paper, we demonstrated the successful deposition of Au NPs, having sizes smaller than 3 nm, onto ZnO NPs. ZnO/Au hybrid nanostructures having different molar ratios of Au to ZnO were synthesized. It was found that Au nanocomponents even at a very low Au/ZnO molar ratio of 0.2% can greatly enhance the photocatalytic and antibacterial activity of ZnO. Electron spin resonance spectroscopy with spin trapping and spin labeling was used to investigate the enhancing effect of Au NPs on the generation of reactive oxygen species and photoinduced charge carriers. Deposition of Au NPs onto ZnO resulted in a dramatic increase in light-induced generation of hydroxyl radical, superoxide and singlet oxygen, and production of holes and electrons. The enhancing effect of Au was dependent on the molar ratio of Au present in the ZnO/Au nanostructures. Consistent with these results from ESR measurements, ZnO/Au nanostructures also exhibited enhanced photocatalytic and antibacterial activity. These results unveiled the enhanced mechanism of Au on ZnO and these materials have great potential for use in water purification and antibacterial products. C1 [He, Weiwei] Xuchang Univ, Inst Surface Micro & Nano Mat, Key Lab Micronano Mat Energy Storage & Convers He, Xuchang 461000, Henan, Peoples R China. [He, Weiwei; Kim, Hyun-Kyung; Warner, Wayne G.; Melka, David; Callahan, John H.; Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Kim, Hyun-Kyung] Minist Food & Drug Safety, Food Safety Bur, Cheongwon 363700, South Korea. RP Yin, JJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM junjie.yin@fda.hhs.gov RI Yin, Jun Jie /E-5619-2014 FU National Natural Science Foundation of China [21303153, 61204009]; Research Project of Basic and Advanced Technology of Henan Province [112300410106]; Korean Government; FDA Nanotechnology CORES Program; Office of Cosmetics and Colors, CFSAN/FDA FX W. He thanks the National Natural Science Foundation of China (Grant No. 21303153 and 61204009) and the Research Project of Basic and Advanced Technology of Henan Province (Grant No. 112300410106) for support. H. K. Kim thanks the support from the Korean Government Scholarship Program. This work was supported by a regulatory science grant under the FDA Nanotechnology CORES Program and by the Office of Cosmetics and Colors, CFSAN/FDA. The authors appreciate Dr. Yongbin Zhang in NCTR/ORA Nanotechnology Core Facility for his assistance with BET measurements and Prof. Zhi Zheng from Xuchang University for his kind discussions. NR 43 TC 120 Z9 123 U1 43 U2 300 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JAN 15 PY 2014 VL 136 IS 2 BP 750 EP 757 DI 10.1021/ja410800y PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 294BY UT WOS:000330018600040 PM 24354568 ER PT J AU Fung, KL Pan, J Ohnuma, S Lund, PE Pixley, JN Kimchi-Sarfaty, C Ambudkar, SV Gottesman, MM AF Fung, King Leung Pan, James Ohnuma, Shinobu Lund, Paul E. Pixley, Jessica N. Kimchi-Sarfaty, Chava Ambudkar, Suresh V. Gottesman, Michael M. TI MDR1 Synonymous Polymorphisms Alter Transporter Specificity and Protein Stability in a Stable Epithelial Monolayer SO CANCER RESEARCH LA English DT Article ID MULTIDRUG-RESISTANCE GENE; P-GLYCOPROTEIN ABCB1; HAPLOTYPE PROFILES; ATP HYDROLYSIS; CELL-LINES; EXPRESSION; BINDING; DRUGS; VARIANT; DISPOSITION AB The drug efflux function of P-glycoprotein (P-gp) encoded by MDR1 can be influenced by genetic polymorphisms, including two synonymous changes in the coding region of MDR1. Here we report that the conformation of P-gp and its drug efflux activity can be altered by synonymous polymorphisms in stable epithelial monolayers expressing P-gp. Several cell lines with similar MDR1 DNA copy number were developed and termed LLC-MDR1-WT (expresses wild-type P-gp), LLC-MDR1-3H (expresses common haplotype P-gp), and LLC-MDR1-3HA (a mutant that carries a different valine codon in position 3435). These cell lines express similar levels of recombinant mRNA and protein. P-gp in each case is localized on the apical surface of polarized cells. However, the haplotype and its mutant P-gps fold differently from the wild-type, as determined by UIC2 antibody shift assays and limited proteolysis assays. Surface biotinylation experiments suggest that the non-wild-type P-gps have longer recycling times. Drug transport assays show that wild-type and haplotype P-gp respond differently to P-gp inhibitors that block efflux of rhodamine 123 or mitoxantrone. In addition, cytotoxicity assays show that the LLC-MDR1-3H cells are more resistant to mitoxantrone than the LLC-MDR1-WT cells after being treated with a P-gp inhibitor. Expression of polymorphic P-gp, however, does not affect the host cell's morphology, growth rate, or monolayer formation. Also, ATPase activity assays indicate that neither basal nor drug-stimulated ATPase activities are affected in the variant P-gps. Taken together, our findings indicate that "silent" polymorphisms significantly change P-gp function, which would be expected to affect interindividual drug disposition and response. (C)2013 AACR. C1 [Fung, King Leung; Pan, James; Ohnuma, Shinobu; Lund, Paul E.; Pixley, Jessica N.; Ambudkar, Suresh V.; Gottesman, Michael M.] NCI, Lab Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kimchi-Sarfaty, Chava] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Lab Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM mgottesman@nih.gov FU Intramural Research Program of the NIH, National Cancer Institute FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute. NR 48 TC 36 Z9 38 U1 1 U2 6 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 JAN 15 PY 2014 VL 74 IS 2 BP 598 EP 608 DI 10.1158/0008-5472.CAN-13-2064 PG 11 WC Oncology SC Oncology GA 294HB UT WOS:000330034200019 PM 24305879 ER PT J AU Balsam, J Rasooly, R Bruck, HA Rasooly, A AF Balsam, Joshua Rasooly, Reuven Bruck, Hugh Alan Rasooly, Avraham TI Thousand-fold fluorescent signal amplification for mHealth diagnostics SO BIOSENSORS & BIOELECTRONICS LA English DT Article DE Lab-on-a-chip; mHealth; Capillary; Fluorescence; Image stacking; Mobile phone ID CELL-PHONE; BIOSENSOR; IMMUNOSENSOR; IMMUNOASSAY; PLATFORM; HEALTH; SENSOR; POINT AB The low sensitivity of Mobile Health (mHealth) optical detectors, such as those found on mobile phones, is a limiting factor for many mHealth clinical applications. To improve sensitivity, we have combined two approaches for optical signal amplification: (1) a computational approach based on an image stacking algorithm to decrease the image noise and enhance weak signals, and (2) an optical signal amplifier utilizing a capillary tube array. These approaches were used in a detection system which includes multi-wavelength LEDs capable of exciting many fluorophores in multiple wavelengths, a mobile phone or a webcam as a detector, and capillary tube array configured with 36 capillary tubes for signal enhancement. The capillary array enables a similar to 100 x increase in signal sensitivity for fluorescein, reducing the limit of detection (LOD) for mobile phones and webcams from 1000 nM to 10 nM. Computational image stacking enables another similar to 10 x increase in signal sensitivity, further reducing the LOD for webcam from 10 nM to 1 nM. To demonstrate the feasibility of the device for the detection of disease-related biomarkers, adenovirus DNA labeled with SYBR green or fluorescein was analyzed by both our capillary array and a commercial plate reader. The LOD for the capillary array was 5 ug/mL, and that of the plate reader was 1 ug/mL. Similar results were obtained using DNA stained with fluorescein. The combination of the two signal amplification approaches enables a similar to 1000 x increase in LOD for the webcam platform. This brings it into the range of a conventional plate reader while using a smaller sample volume (10 ul) than the plate reader requires (100 ul). This suggests that such a device could be suitable for biosensing applications where up to 10 fold smaller sample sizes are needed. The simple optical configuration for mHealth described in this paper employing the combined capillary and image processing signal amplification is capable of measuring weak fluorescent signals without the need of dedicated laboratories. It has the potential to be used to increase sensitivity of other optically based mHealth technologies, and may increase mHealth's clinical utility, especially for telemedicine and for resource-poor settings and global health applications. Published by Elsevier B.V. C1 [Balsam, Joshua; Rasooly, Avraham] FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. [Balsam, Joshua; Bruck, Hugh Alan] Univ Maryland, College Pk, MD 20742 USA. [Rasooly, Reuven] ARS, Western Reg Res Ctr, USDA, Albany, CA 94710 USA. [Rasooly, Avraham] NCI, Div Canc Biol, Bethesda, MD 20892 USA. RP Rasooly, A (reprint author), FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. EM rasoolya@mail.nih.gov FU FDA's Center for Devices and Radiological Health, Division of Biology; National Cancer Institute FX This work was supported by the FDA's Center for Devices and Radiological Health, Division of Biology and the National Cancer Institute. The views expressed are those of the authors and do not represent those of the U.S. Government. NR 35 TC 9 Z9 9 U1 5 U2 84 PU ELSEVIER ADVANCED TECHNOLOGY PI OXFORD PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-5663 EI 1873-4235 J9 BIOSENS BIOELECTRON JI Biosens. Bioelectron. PD JAN 15 PY 2014 VL 51 BP 1 EP 7 DI 10.1016/j.bios.2013.06.053 PG 7 WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical; Electrochemistry; Nanoscience & Nanotechnology SC Biophysics; Biotechnology & Applied Microbiology; Chemistry; Electrochemistry; Science & Technology - Other Topics GA 251CN UT WOS:000326905500001 PM 23928092 ER PT J AU Warfel, JM Zimmerman, LI Merkel, TJ AF Warfel, Jason M. Zimmerman, Lindsey I. Merkel, Tod J. TI Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE whooping cough; T-cell memory; animal models; adaptive immunity; IL-17 ID BORDETELLA-PERTUSSIS; WHOLE-CELL; CONTROLLED TRIAL; IMMUNITY; VACCINATION; CHILDREN; RESURGENCE; DIPHTHERIA; RESPONSES; INFANTS AB Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have been rising and reached a 50-y high of 42,000 cases in 2012. Although pertussis resurgence is not completely understood, we hypothesize that current acellular pertussis (aP) vaccines fail to prevent colonization and transmission. To test our hypothesis, infant baboons were vaccinated at 2, 4, and 6 mo of age with aP or whole-cell pertussis (wP) vaccines and challenged with B. pertussis at 7 mo. Infection was followed by quantifying colonization in nasopharyngeal washes and monitoring leukocytosis and symptoms. Baboons vaccinated with aP were protected from severe pertussis-associated symptoms but not from colonization, did not clear the infection faster than naive animals, and readily transmitted B. pertussis to unvaccinated contacts. Vaccination with wP induced a more rapid clearance compared with naive and aP-vaccinated animals. By comparison, previously infected animals were not colonized upon secondary infection. Although all vaccinated and previously infected animals had robust serum antibody responses, we found key differences in T-cell immunity. Previously infected animals and wP-vaccinated animals possess strong B. pertussis-specific T helper 17 (Th17) memory and Th1 memory, whereas aP vaccination induced a Th1/Th2 response instead. The observation that aP, which induces an immune response mismatched to that induced by natural infection, fails to prevent colonization or transmission provides a plausible explanation for the resurgence of pertussis and suggests that optimal control of pertussis will require the development of improved vaccines. C1 [Warfel, Jason M.; Zimmerman, Lindsey I.; Merkel, Tod J.] US EPA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Merkel, TJ (reprint author), US EPA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM tod.merkel@fda.hhs.gov RI Chiang, Vincent, Ming-Hsien/D-4312-2016 OI Chiang, Vincent, Ming-Hsien/0000-0002-2029-7863 FU Food and Drug Administration; National Institutes of Health/National Institute of Allergy and Infectious Diseases [Y1-AI-1727-01]; National Institutes of Health National Center for Research Resources [P40RR012317, 5R24RR016556-10] FX We thank Dr. John Dennis, Dr. Jill Ascher, Lewis Shankle, Perry Altland, and Ernest Madison for technical assistance. We thank Dr. Gary White, Dr. Roman Wolf, and Dr. James Papin for technical assistance and critical discussions. We thank Dr. Drusilla Burns and Dr. Scott Stibitz for critical reading of the manuscript. This work was funded by the Food and Drug Administration and National Institutes of Health/National Institute of Allergy and Infectious Diseases through Interagency Agreement Y1-AI-1727-01. Baboons were obtained from the Oklahoma Baboon Research Resource. The Oklahoma Baboon Research Resource was supported by Grants P40RR012317 and 5R24RR016556-10 from the National Institutes of Health National Center for Research Resources. NR 54 TC 136 Z9 137 U1 2 U2 21 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 14 PY 2014 VL 111 IS 2 BP 787 EP 792 DI 10.1073/pnas.1314688110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 288LW UT WOS:000329614500054 PM 24277828 ER PT J AU Ramirez-Lee, MA Rosas-Hernandez, H Salazar-Garcia, S Gutierrez-Hernandez, JM Espinosa-Tanguma, R Gonzalez, FJ Ali, SF Gonzalez, C AF Ramirez-Lee, Manuel A. Rosas-Hernandez, Hector Salazar-Garcia, Samuel Manuel Gutierrez-Hernandez, Jose Espinosa-Tanguma, Ricardo Gonzalez, Francisco J. Ali, Syed F. Gonzalez, Carmen TI Silver nanoparticles induce anti-proliferative effects on airway smooth muscle cells. Role of nitric oxide and muscarinic receptor signaling pathway SO TOXICOLOGY LETTERS LA English DT Article DE Nitric oxide; Muscarinic receptor; Silver nanoparticles; Airway; Proliferation; Apoptosis ID ALVEOLAR EPITHELIAL-CELLS; SPRAGUE-DAWLEY RATS; INHALATION TOXICITY; OXIDATIVE STRESS; LUNG-FUNCTION; ASTHMA; INFLAMMATION; ACTIVATION; INHIBITION; PATHOPHYSIOLOGY AB Silver nanoparticles (AgNPs) are used to manufacture materials with new properties and functions. However, little is known about their toxic or beneficial effects on human health, especially in the respiratory system, where its smooth muscle (ASM) regulates the airway contractility by different mediators, such as acetylcholine (ACh) and nitric oxide (NO). The aim of this study was to evaluate the effects of AgNPs on ASM cells. Exposure to AgNPs induced ACh-independent expression of the inducible nitric oxide synthase (iNOS) at 100 mu g/mL, associated with excessive production of NO. AgNPs induced the muscarinic receptor activation, since its blockage with atropine and blockage of its downstream signaling pathway inhibited the NO production. AgNPs at 10 and 100 mu g/mL induced ACh-independent prolonged cytotoxicity and decreased cellular proliferation mediated by the muscarinic receptor-iNOS pathway. However, the concentration of 100 mu g/mL of AgNPs induced muscarinic receptor-independent apoptosis, suggesting the activation of multiple pathways. These data indicate that AgNPs induce prolonged cytotoxic and anti-proliferative effects on ASM cells, suggesting an activation of the muscarinic receptor-iNOS pathway. Further investigation is required to understand the full mechanisms of action of AgNPs on ASM under specific biological conditions. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Ramirez-Lee, Manuel A.; Rosas-Hernandez, Hector; Salazar-Garcia, Samuel; Gonzalez, Carmen] Univ Autonoma San Luis Potosi, Fac Ciencias Quim, San Luis Potosi 78210, Mexico. [Espinosa-Tanguma, Ricardo] Univ Autonoma San Luis Potosi, Fac Med, San Luis Potosi 78210, Mexico. [Manuel Gutierrez-Hernandez, Jose; Gonzalez, Francisco J.] Univ Autonoma San Luis Potosi, San Luis Potosi 78210, Mexico. [Rosas-Hernandez, Hector; Ali, Syed F.; Gonzalez, Carmen] US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Gonzalez, C (reprint author), Univ Autonoma San Luis Potosi, Fac Ciencias Quim, Av Manuel Nava 6, San Luis Potosi 78210, Mexico. EM cgonzalez.uaslp@gmail.com RI Hector, Rosas-Hernandez/J-5130-2015; OI Rosas-Hernandez, Hector/0000-0002-2736-8302 FU Integral Program for Institutional Support [C10-PIFI-03.02.02]; National Council of Science and Technology of Mexico [407087] FX We want to thank to Mr. Daniel Alberto Maldonado Ortega for technical assistance. This work was supported by Integral Program for Institutional Support Grant C10-PIFI-03.02.02 and National Council of Science and Technology of Mexico Fellowship for Manuel Alejandro Ramirez Lee (407087). NR 77 TC 9 Z9 9 U1 0 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 EI 1879-3169 J9 TOXICOL LETT JI Toxicol. Lett. PD JAN 13 PY 2014 VL 224 IS 2 BP 246 EP 256 DI 10.1016/j.toxlet.2013.10.027 PG 11 WC Toxicology SC Toxicology GA 264OV UT WOS:000327889300011 PM 24188929 ER PT J AU Jitian, S White, SR Yang, HHW Weisz, A AF Jitian, Simion White, Samuel R. Yang, H. -H. Wendy Weisz, Adrian TI Conventional high-performance liquid chromatography versus derivative spectrophotometry for the determination of 1,3,6-pyrenetrisulfonic acid trisodium salt and 1,3,6,8-pyrenetetrasulfonic acid tetrasodium salt in the color additive D&C Green No. 8 (Pyranine) SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc, Amer Chem Soc, Div Chem Educ DE D&C Green No. 8; Pyranine; 1,3,6-Pyrenetrisulfonic acid sodium salt; 1,3,6,8-Pyrenetetrasulfonic acid sodium salt; HPLC; Derivative spectrophotometry ID SUBSIDIARY COLORS; PHLOXINE-B; PRODUCTS; IDENTIFICATION; HPLC AB Specifications in the U.S. Code of Federal Regulations for the color additive D&C Green No. 8 (Colour Index No. 59040) limit the levels of the subsidiary colors 1,3,6-pyrenetrisulfonic acid trisodium salt (P3S) and 1,3,6,8-pyrenetetrasulfonic acid tetrasodium salt (P4S). The present paper describes a comparative study of two possible methods to replace the currently used multi-step TLC/spectrophotometry method of separating and quantifying the minor components P3S and P4S in G8. One of the new approaches uses conventional high-performance liquid chromatography (HPLC) and the other, derivative spectrophotometry. While the derivative spectrophotometric method was shown to be inadequate for the analysis of minor components overwhelmed by components of much higher concentration, the HPLC method was proven highly effective. The closely related, very polar compounds P3S and P4S were separated by the new HPLC method in less than 4 min using a conventional HPLC instrument. P3S and P4S were quantified by using five-point calibration curves with data points that ranged from 0.45 to 7.63% and from 0.13 to 1.82%, by weight, for P3S and P4S, respectively. The HPLC method was applied to the analysis of test portions from 20 batches of D&C Green No. 8 submitted to the U.S. Food and Drug Administration for certification. Published by Elsevier B.V. C1 [Jitian, Simion] Politehn Univ Timisoara, Fac Engn Hunedoara, Timisoara, Romania. [White, Samuel R.; Yang, H. -H. Wendy; Weisz, Adrian] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Weisz, A (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM adrian.weisz@fda.hhs.gov NR 19 TC 1 Z9 1 U1 2 U2 16 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 10 PY 2014 VL 1324 BP 238 EP 241 DI 10.1016/j.chroma.2013.11.033 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 297LE UT WOS:000330256100031 PM 24315677 ER PT J AU Jin, TC Wang, Y Chen, YW Fu, TJ Kothary, MH McHugh, TH Zhang, YZ AF Jin, Tengchuan Wang, Yang Chen, Yu-Wei Fu, Tong-Jen Kothary, Mahendra H. McHugh, Tara H. Zhang, Yuzhu TI Crystal Structure of Korean Pine (Pinus koraiensis) 7S Seed Storage Protein with Copper Ligands SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE 7S vicilin; pine nut; allergen; X-ray crystallography; copper protein ID MAJOR PEANUT ALLERGEN; ARA H 1; TREE NUT ALLERGENS; CHEMICAL-COMPOSITION; MOLECULAR GRAPHICS; FOOD ALLERGY; PROGRAM; VICILIN; CRYSTALLIZATION; PURIFICATION AB The prevalence of food allergy has increased in recent years, and Korean pine vicilin is a potential food allergen. We have previously reported the crystallization of Korean pine vicilin purified from raw pine nut. Here we report the isolation of vicilin mRNA and the crystal structure of Korean pine vicilin at 2.40 angstrom resolution. The overall structure of pine nut vicilin is similar to the structures of other 7S seed storage proteins and consists of an N-terminal domain and a C-terminal domain. Each assumes a cupin fold, and they are symmetrically related about a pseudodyad axis. Three vicilin molecules form a doughnut-shaped trimer through head-to-tail association. Structure characterization of Korean pine nut vicilin unexpectedly showed that, in its native trimeric state, the vicilin has three copper ligands. Sequence alignments suggested that the copper-coordinating residues were conserved in winter squash, sesame, tomato, and several tree nuts, while they were not conserved in a number of legumes, including peanut and soybean. Additional studies are needed to assess whether the copper-coordinating property of vicilins has a biological function in the relevant plants. The nutritional value of this copper-coordinating protein in tree nuts and other edible seeds may be worth further investigations. C1 [Jin, Tengchuan; Wang, Yang; Chen, Yu-Wei] IIT, Dept Biol, Chicago, IL 60616 USA. [Fu, Tong-Jen] US FDA, Ctr Food Safety & Appl Nutr, Bedford Pk, IL 60501 USA. [Kothary, Mahendra H.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [McHugh, Tara H.; Zhang, Yuzhu] ARS, Western Reg Res Ctr, USDA, Albany, CA 94710 USA. RP Jin, TC (reprint author), NIAID, Struct Immunobiol Unit, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM tengchuan@gmail.com; yuzhu.zhang@ars.usda.gov RI Jin, Tengchuan/B-5883-2014; OI Jin, Tengchuan/0000-0002-1395-188X; Zhang, Yuzhu/0000-0001-7882-5692 FU U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]; Illinois Institute of Technology; U.S. Food and Drug Administration [5U01FD003801]; Institute for Food Safety and Health, Illinois Institute of Technology [5U01FD003801] FX Use of the APS was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract W-31-109-Eng-38. This work was partially supported by a fund from the Illinois Institute of Technology and by Cooperative Agreement 5U01FD003801 between the U.S. Food and Drug Administration and Institute for Food Safety and Health, Illinois Institute of Technology. NR 55 TC 7 Z9 7 U1 3 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 JAN 8 PY 2014 VL 62 IS 1 BP 222 EP 228 DI 10.1021/jf4039887 PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 288BK UT WOS:000329586800028 PM 24328105 ER PT J AU Zhao, Z Zhong, LL Elrod, E Struble, E Ma, L Yan, HL Harman, C Deng, L Virata-Theimer, ML Liu, P Alter, H Grakoui, A Zhang, P AF Zhao, Zhong Zhong, Lilin Elrod, Elizabeth Struble, Evi Ma, Li Yan, Hailing Harman, Christine Deng, Lu Virata-Theimer, Maria Luisa Liu, Peter Alter, Harvey Grakoui, Arash Zhang, Pei TI A Neutralization Epitope in the Hepatitis C Virus E2 Glycoprotein Interacts with Host Entry Factor CD81 SO PLOS ONE LA English DT Article ID ENVELOPE GLYCOPROTEIN; VIRAL ENTRY; ANTIBODIES; BINDING; PARTICLES; INFECTION; PLASMA; GENOTYPES; RECEPTOR; PROGRESS AB The identification of a specific immunogenic candidate that will effectively activate the appropriate pathway for neutralizing antibody production is fundamental for vaccine design. By using a monoclonal antibody (1H8) that neutralizes HCV in vitro, we have demonstrated here that 1H8 recognized an epitope mapped between residues A524 and W529 of the E2 protein. We also found that the epitope residues A524, P525, Y527 and W529 were crucial for antibody binding, while the residues T526, Y527 and W529 within the same epitope engaged in the interaction with the host entry factor CD81. Furthermore, we detected "1H8-like" antibodies, defined as those with amino acid-specificity similar to 1H8, in the plasma of patients with chronic HCV infection. The time course study of plasma samples from Patient H, a well-characterized case of post-transfusion hepatitis C, showed that "1H8-like" antibodies could be detected in a sample collected almost two years after the initial infection, thus confirming the immunogenicity of this epitope in vivo. The characterization of this neutralization epitope with a function in host entry factor CD81 interaction should enhance our understanding of antibody-mediated neutralization of HCV infections. C1 [Zhao, Zhong; Zhong, Lilin; Struble, Evi; Ma, Li; Yan, Hailing; Harman, Christine; Deng, Lu; Virata-Theimer, Maria Luisa; Liu, Peter; Zhang, Pei] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Off Blood Res & Review, Bethesda, MD 20892 USA. [Elrod, Elizabeth; Grakoui, Arash] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA. [Alter, Harvey] NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Zhang, P (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Off Blood Res & Review, Bethesda, MD 20892 USA. EM pei.zhang@fda.hhs.gov FU Modernizing Science Funds of the Food and Drug Administration FX This study was supported by the Modernizing Science Funds of the Food and Drug Administration. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 4 Z9 4 U1 0 U2 9 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 6 PY 2014 VL 9 IS 1 AR e84346 DI 10.1371/journal.pone.0084346 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 286IW UT WOS:000329462700018 PM 24400084 ER PT J AU Wang, SJ Dmitrienko, A AF Wang, Sue-Jane Dmitrienko, Alex TI GUEST EDITORS' NOTE: SPECIAL ISSUE ON SUBGROUP ANALYSIS IN CLINICAL TRIALS SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Editorial Material C1 [Wang, Sue-Jane] US FDA, Silver Spring, MD 20993 USA. [Dmitrienko, Alex] Quintiles, Durham, NC USA. RP Wang, SJ (reprint author), US FDA, Silver Spring, MD 20993 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 520 CHESTNUT 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 2014 VL 24 IS 1 SI SI BP 1 EP 3 DI 10.1080/10543406.2014.858958 PG 3 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA AH2EB UT WOS:000335932400001 PM 24392974 ER PT J AU Wang, SJ Hung, HMJ AF Wang, Sue-Jane Hung, H. M. James TI A REGULATORY PERSPECTIVE ON ESSENTIAL CONSIDERATIONS IN DESIGN AND ANALYSIS OF SUBGROUPS WHEN CORRECTLY CLASSIFIED SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Biomarker; Formation of subgroup; Interaction-to-overall effects ratio; Predictive of treatment effect; Subgroup-specific treatment effect hypothesis ID RANDOMIZED CLINICAL-TRIALS; CHALLENGES; STRATEGIES; ONCOLOGY AB This regulatory research provides possible approaches for improvement to conventional subgroup analysis in a fixed design setting. The interaction-to-overall effects ratio is recommended in the planning stage for potential predictors whose prevalence is at most 50% and its observed ratio is recommended in the analysis stage for proper subgroup interpretation if sample size is only planned to target the overall effect size. We illustrate using regulatory examples and underscore the importance of striving for balance between safety and efficacy when considering a regulatory recommendation of a label restricted to a subgroup. A set of decision rules gives guidance for rigorous subgroup-specific conclusions. C1 [Wang, Sue-Jane] US FDA, Off Biostat, OTS, CDER, Silver Spring, MD 20993 USA. [Hung, H. M. James] US FDA, Div Biometr 1, OB, OTS,CDER, Silver Spring, MD 20993 USA. RP Wang, SJ (reprint author), US FDA, Off Biostat, OTS, CDER, 10903 New Hampshire Ave,Bldg 21,HFD 710, Silver Spring, MD 20993 USA. EM suejane.wang@fda.hhs.gov FU RSR funds provided by the Center for Drug Evaluation and Research of the U.S. Food and Drug Administration [05-02, 05-14] FX The regulatory research work presented here was supported by the RSR funds 05-02 and 05-14, provided by the Center for Drug Evaluation and Research of the U.S. Food and Drug Administration. This article reflects the views of the authors and should not be construed to represent the views or policies of the U.S. Food and Drug Administration. NR 35 TC 6 Z9 6 U1 1 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 520 CHESTNUT 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 2014 VL 24 IS 1 SI SI BP 19 EP 41 DI 10.1080/10543406.2013.856022 PG 23 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA AH2EB UT WOS:000335932400003 PM 24392976 ER PT J AU Varadhan, R Wang, SJ AF Varadhan, Ravi Wang, Sue-Jane TI STANDARDIZATION FOR SUBGROUP ANALYSIS IN RANDOMIZED CONTROLLED TRIALS SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Confounding; Consistency of treatment effect; Forest plot; Heterogeneity of treatment effects; Interaction; Marginal structural model ID MARGINAL STRUCTURAL MODELS AB Randomized controlled trials (RCTs) emphasize the average or overall effect of a treatment (ATE) on the primary endpoint. Even though the ATE provides the best summary of treatment efficacy, it is of critical importance to know whether the treatment is similarly efficacious in important, predefined subgroups. This is why the RCTs, in addition to the ATE, also present the results of subgroup analysis for preestablished subgroups. Typically, these are marginal subgroup analysis in the sense that treatment effects are estimated in mutually exclusive subgroups defined by only one baseline characteristic at a time (e.g., men versus women, young versus old). Forest plot is a popular graphical approach for displaying the results of subgroup analysis. These plots were originally used in meta-analysis for displaying the treatment effects from independent studies. Treatment effect estimates of different marginal subgroups are, however, not independent. Correlation between the subgrouping variables should be addressed for proper interpretation of forest plots, especially in large effectiveness trials where one of the goals is to address concerns about the generalizability of findings to various populations. Failure to account for the correlation between the subgrouping variables can result in misleading (confounded) interpretations of subgroup effects. Here we present an approach called standardization, a commonly used technique in epidemiology, that allows for valid comparison of subgroup effects depicted in a forest plot. We present simulations results and a subgroup analysis from parallel-group, placebo-controlled randomized trials of antibiotics for acute otitis media. C1 [Varadhan, Ravi] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Ctr Aging & Hlth, Baltimore, MD USA. [Varadhan, Ravi] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Wang, Sue-Jane] US FDA, Off Biostat, Off Translat Serv, Ctr Drug Evaluat & Res, Washington, DC 20204 USA. [Wang, Sue-Jane] Johns Hopkins Univ, Engn Program Profess, Baltimore, MD USA. [Wang, Sue-Jane] Johns Hopkins Univ, Appl Sci Program Profess, Baltimore, MD USA. RP Varadhan, R (reprint author), Suite 2-700,2024 E Monument St, Baltimore, MD 21205 USA. EM rvaradhan@jhmi.edu FU Food and Drug Administration, Department of Health and Human Services [HHSF2232010000072C]; RSR grant awarded by the Center for Drug Evaluation and Research, US Food and Drug Administration [08-48] FX The analyses upon which this publication is based were performed under contract HHSF2232010000072C, entitled "Partnership in Applied Comparative Effectiveness Science," sponsored by the Food and Drug Administration, Department of Health and Human Services. This research was also supported by the RSR grant 08-48 awarded by the Center for Drug Evaluation and Research, US Food and Drug Administration. Ravi Varadhan is a Brookdale Leadership in Aging Fellow at the Johns Hopkins University. NR 6 TC 4 Z9 4 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 520 CHESTNUT 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 2014 VL 24 IS 1 SI SI BP 154 EP 167 DI 10.1080/10543406.2013.856023 PG 14 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA AH2EB UT WOS:000335932400010 PM 24392983 ER PT J AU Chen, S Melchior, WB Guo, L AF Chen, Si Melchior, William B., Jr. Guo, Lei TI Endoplasmic Reticulum Stress in Drug- and Environmental Toxicant-Induced Liver Toxicity SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE signaling pathways; Endoplasmic reticulum (ER) stress; liver toxicity ID UNFOLDED PROTEIN RESPONSE; HUMAN HEPATIC CELLS; ACETAMINOPHEN-INDUCED HEPATOTOXICITY; TRANSCRIPTION FACTOR XBP-1; OF-THE-LITERATURE; ER STRESS; GENE-EXPRESSION; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; MESSENGER-RNA AB Liver injury resulting from exposure to drugs and environmental chemicals is a major health problem. Endoplasmic reticulum stress (ER stress) is considered to be an important factor in a wide range of diseases, such as cancer, neurological and cardiovascular disease, diabetes, and inflammatory diseases. The role of ER stress in drug-induced and environmental toxicant-induced liver toxicity has been underestimated in the past; emerging evidence indicates that ER stress makes a substantial contribution to the pathogenesis of drug-induced liver toxicity. In this review, we summarize current knowledge on drugs and environmental toxicants that trigger ER stress in liver and on the underlying molecular mechanisms. We also discuss experimental approaches for ER stress studies. C1 [Chen, Si; Melchior, William B., Jr.; Guo, Lei] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Guo, L (reprint author), 3900 NCTR Rd HFT-110, Jefferson, AR 72079 USA. EM Lei.Guo@fda.hhs.gov FU US Department of Energy; US FDA FX SC was supported by appointments to the Postgraduate Research Program at the National Center for Toxicological Research administered by the Oak Ridge Institute for Science Education through an interagency agreement between the US Department of Energy and the US FDA. NR 150 TC 11 Z9 11 U1 0 U2 13 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 520 CHESTNUT 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 2014 VL 32 IS 1 BP 83 EP 104 DI 10.1080/10590501.2014.881648 PG 22 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA AC1QE UT WOS:000332270300003 PM 24598041 ER PT J AU Zhou, C Wang, JW Sun, N Tian, J Wang, J Lv, YS Wang, P Huang, KL Che, HL AF Zhou, Cui Wang, Jianwu Sun, Na Tian, Jing Wang, Jing Lv, Yingshuang Wang, Peng Huang, Kunlun Che, Huilian TI Allergenicity of recombinant human lactoferrin to an animal model Brown Norway rats SO FOOD AND AGRICULTURAL IMMUNOLOGY LA English DT Article DE recombinant human lactoferrin; BN rat; allergenicity ID GENETICALLY-MODIFIED CROPS; ORAL SENSITIZATION; ANTIBODY-RESPONSES; PROTEIN ALLERGENICITY; FOOD PROTEINS; ALLERGIC INFLAMMATION; DIETARY CONTROL; MAST-CELLS; T-CELLS; MICE AB The assessment of allergenicity of recombinant human lactoferrin (rhLF) using an animal model for its extensive use. In this study, 32 Brown Norway (BN) rats were divided into four groups that were exposed to ovalbumin (OVA) (positive control), rhLF, bovine lactoferrin (bLF) and saline (negative control), respectively, with daily intragastric administration for 42 days. The level of specific antibody (IgE, IgG and IgG2a), blood cell counts, blood pressure and pathology of important organs were measured and compared among the groups. OVA stimulated significant higher levels of specific-IgE and eosinophil (EO) counts (p <0.05), lower blood pressure (p<0.05) and more serious lesion in the lung of BN rats compared to the other groups. And the animals did not show obvious humeral, cell-mediated and local allergic response to rhLF and bLF. The results demonstrate a weak allergenicity of rhLF on the animal and reveal its potential value for further identified study. C1 [Zhou, Cui; Sun, Na; Wang, Jing; Huang, Kunlun; Che, Huilian] China Agr Univ, Coll Food Sci & Nutr Engn, Beijing 100094, Peoples R China. [Wang, Jianwu] Chinese Acad Sci, Inst Zool, Beijing, Peoples R China. [Wang, Jianwu] China Agr Univ, State Key Lab AgroBiotechnol, Beijing 100094, Peoples R China. [Tian, Jing] Herbin Med Univ, Dept Dermatol, Affiliated Hosp 1, Harbin, Peoples R China. [Lv, Yingshuang; Wang, Peng] US FDA, Inst Food Safety & Hlth, Summi Argo, IL USA. [Lv, Yingshuang; Wang, Peng] IIT, Summi Argo, IL USA. [Huang, Kunlun; Che, Huilian] Minist Agr, Supervis Inspect & Testing Ctr Genetically Modifi, Beijing, Peoples R China. RP Che, HL (reprint author), China Agr Univ, Coll Food Sci & Nutr Engn, Beijing 100094, Peoples R China. EM chehuilian@cau.edu.cn FU Key Program of National Natural Science Funds of China [81072305] FX This work was supported by a grant from the Key Program of National Natural Science Funds of China (No.81072305). We acknowledge all colleagues who contributed to the LF project and participated in the allergenicity assessment of rhLF. NR 51 TC 0 Z9 1 U1 0 U2 8 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0954-0105 EI 1465-3443 J9 FOOD AGR IMMUNOL JI Food Agric. Immunol. PD JAN 2 PY 2014 VL 25 IS 1 BP 34 EP 48 DI 10.1080/09540105.2012.733352 PG 15 WC Chemistry, Applied; Food Science & Technology; Immunology; Toxicology SC Chemistry; Food Science & Technology; Immunology; Toxicology GA 287MM UT WOS:000329545900004 ER PT B AU Almuti, K Rahman, S Acosta, D AF Almuti, Khalid Rahman, Shahid Acosta, Daniel, Jr. BE Hayes, AW Kruger, CL TI Pathophysiology and Toxicology of the Heart SO HAYES' PRINCIPLES AND METHODS OF TOXICOLOGY, 6TH EDITION LA English DT Article; Book Chapter DE Arrhythmia; Cardiomyopathy; Torsades de Pointes (TdP); Ischemia; Ethanol; Cocaine; Anthracyclines; Myocardial infarction ID SOCIETY-OF-CARDIOLOGY; EUROPEAN-SOCIETY; ALCOHOLIC CARDIOMYOPATHY; ANTIARRHYTHMIC DRUGS; ATRIAL TACHYCARDIA; QT-INTERVAL; APOPTOSIS; ARRHYTHMIAS; METALLOTHIONEIN; MECHANISMS C1 [Almuti, Khalid] Univ Cincinnati, Hlth Phys Off, Cincinnati, OH 45220 USA. [Rahman, Shahid] Univ Cincinnati, Div Cardiovasc Dis, Cincinnati, OH USA. [Acosta, Daniel, Jr.] US FDA, Res Off, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Almuti, K (reprint author), Univ Cincinnati, Hlth Phys Off, Cincinnati, OH 45220 USA. NR 49 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 978-1-84214-537-1; 978-1-84214-536-4 PY 2014 BP 1567 EP 1577 D2 10.1201/b17359 PG 11 WC Toxicology SC Toxicology GA BD7FA UT WOS:000362973800033 ER PT B AU Volpe, DA Shen, H Balimane, PV AF Volpe, Donna A. Shen, Hong Balimane, Praveen V. BE Wang, J Urban, L TI EVALUATION OF THE COLLECTIVE IMPACT OF PASSIVE PERMEABILITY AND ACTIVE TRANSPORT ON IN VIVO BLOOD-BRAIN BARRIER AND GASTROINTESTINAL DRUG ABSORPTION SO PREDICTIVE ADMET: INTEGRATIVE APPROACHES IN DRUG DISCOVERY AND DEVELOPMENT LA English DT Article; Book Chapter ID GLYCOPROTEIN-MEDIATED TRANSPORT; HUMAN INTESTINAL-ABSORPTION; CANCER RESISTANCE PROTEIN; MDR1A P-GLYCOPROTEIN; CACO-2 CELL-CULTURE; ARTIFICIAL MEMBRANE; CEREBROSPINAL-FLUID; UNBOUND CONCENTRATION; ENDOTHELIAL-CELLS; ORAL ABSORPTION C1 [Volpe, Donna A.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Shen, Hong; Balimane, Praveen V.] Bristol Myers Squibb Co, Princeton, NJ USA. RP Volpe, DA (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 108 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-78330-6; 978-1-118-29992-0 PY 2014 BP 263 EP 290 D2 10.1002/9781118783344 PG 28 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BD7FW UT WOS:000363025900014 ER PT B AU Makris, SL Harrouk, W AF Makris, Susan L. Harrouk, Wafa BE Hoyer, PB TI Assessing Ovarian Toxicity in Human Health Risk Assessment for Environmental Chemicals and Pharmaceuticals SO OVARIAN TOXICOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID HORMONE REPLACEMENT THERAPY; FEMALE REPRODUCTIVE-SYSTEM; COLLABORATIVE WORK; 4-VINYLCYCLOHEXENE DIEPOXIDE; DI-(2-ETHYLHEXYL) PHTHALATE; PUBERTAL DEVELOPMENT; FOLLICLE COUNTS; POSITION PAPER; WISTAR RATS; FERTILITY C1 [Makris, Susan L.] US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA. [Harrouk, Wafa] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Makris, SL (reprint author), US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA. NR 129 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 978-1-4665-0407-3; 978-1-4665-0406-6 PY 2014 BP 335 EP 361 PG 27 WC Obstetrics & Gynecology; Toxicology SC Obstetrics & Gynecology; Toxicology GA BD6DH UT WOS:000362091400016 ER PT B AU Chen, Y Son, I AF Chen, Yi Son, Insook BE Oyarzabal, OA Kathariou, S TI Polymerase Chain Reaction-Based Subtyping Methods SO DNA METHODS IN FOOD SAFETY: MOLECULAR TYPING OF FOODBORNE AND WATERBORNE BACTERIAL PATHOGENS LA English DT Article; Book Chapter ID FRAGMENT-LENGTH-POLYMORPHISM; FIELD GEL-ELECTROPHORESIS; TANDEM-REPEAT ANALYSIS; LOCUS VARIABLE-NUMBER; SEQUENCE-BASED PCR; RESISTANT STAPHYLOCOCCUS-AUREUS; LISTERIA-MONOCYTOGENES STRAINS; MOLECULAR TYPING METHODS; ESCHERICHIA-COLI O157; COMMERCIAL SOFTWARE PACKAGES C1 [Chen, Yi; Son, Insook] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Chen, Y (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 102 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, WEST SUSSEX PO19 8SQ, ENGLAND BN 978-1-118-27866-6; 978-1-118-27867-3 PY 2014 BP 3 EP 26 D2 10.1002/9781118278666 PG 24 WC Biochemical Research Methods; Food Science & Technology; Microbiology SC Biochemistry & Molecular Biology; Food Science & Technology; Microbiology GA BD8IU UT WOS:000363969200002 ER PT B AU Gopinath, G Hari, K Jain, R Kothary, MH Jarvis, KG Franco, AA Grim, CJ Sathyamoorthy, V Mammel, MK Datta, AR McCardell, BA Solomotis, MD Tall, BD AF Gopinath, G. Hari, K. Jain, R. Kothary, M. H. Jarvis, K. G. Franco, A. A. Grim, C. J. Sathyamoorthy, V. Mammel, M. K. Datta, A. R. McCardell, B. A. Solomotis, M. D. Tall, Ben D. BE Oyarzabal, OA Kathariou, S TI Databases and Internet Applications SO DNA METHODS IN FOOD SAFETY: MOLECULAR TYPING OF FOODBORNE AND WATERBORNE BACTERIAL PATHOGENS LA English DT Article; Book Chapter ID UNITED-STATES; BIOINFORMATICS RESOURCE; FOODBORNE ILLNESS; PULSENET; DISEASES; SURVEILLANCE; INFORMATION; COLLECTION; PATHOGENS; INSTITUTE C1 [Gopinath, G.; Kothary, M. H.; Jarvis, K. G.; Franco, A. A.; Grim, C. J.; Sathyamoorthy, V.; Mammel, M. K.; Datta, A. R.; McCardell, B. A.; Solomotis, M. D.; Tall, Ben D.] US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Hari, K.; Jain, R.] CBio Inc, Fremont, CA USA. RP Gopinath, G (reprint author), US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. OI Tall, Ben/0000-0003-0399-3629 NR 41 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, WEST SUSSEX PO19 8SQ, ENGLAND BN 978-1-118-27866-6; 978-1-118-27867-3 PY 2014 BP 113 EP 132 D2 10.1002/9781118278666 PG 20 WC Biochemical Research Methods; Food Science & Technology; Microbiology SC Biochemistry & Molecular Biology; Food Science & Technology; Microbiology GA BD8IU UT WOS:000363969200007 ER PT B AU Lynne, AM Han, J Foley, SL AF Lynne, Aaron M. Han, Jing Foley, Steven L. BE Oyarzabal, OA Kathariou, S TI Salmonella SO DNA METHODS IN FOOD SAFETY: MOLECULAR TYPING OF FOODBORNE AND WATERBORNE BACTERIAL PATHOGENS LA English DT Article; Book Chapter ID FIELD GEL-ELECTROPHORESIS; FRAGMENT-LENGTH-POLYMORPHISM; ENTERICA SUBSP ENTERICA; TANDEM REPEAT ANALYSIS; RESTRICTION-SITE PCR; SEQUENCE-BASED PCR; ESCHERICHIA-COLI; VARIABLE-NUMBER; RESISTANT SALMONELLA; SEROTYPE ENTERITIDIS C1 [Lynne, Aaron M.] Sam Houston State Univ, Dept Biol Sci, Huntsville, TX 77340 USA. [Han, Jing; Foley, Steven L.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Lynne, AM (reprint author), Sam Houston State Univ, Dept Biol Sci, Huntsville, TX 77340 USA. NR 96 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, WEST SUSSEX PO19 8SQ, ENGLAND BN 978-1-118-27866-6; 978-1-118-27867-3 PY 2014 BP 337 EP 357 D2 10.1002/9781118278666 PG 21 WC Biochemical Research Methods; Food Science & Technology; Microbiology SC Biochemistry & Molecular Biology; Food Science & Technology; Microbiology GA BD8IU UT WOS:000363969200015 ER PT S AU Zhou, WL Chang, EY Wang, PG AF Zhou, Wanlong Chang, Eugene Y. Wang, Perry G. BE Wang, PG Vitha, MF Kay, JF TI INTRODUCTION: BASIC PRINCIPLES OF ASSAYS TO BE COVERED, SAMPLE HANDLING, AND SAMPLE PROCESSING SO HIGH-THROUGHPUT ANALYSIS FOR FOOD SAFETY SE Chemical Analysis-A Series of Monographs on Analytical Chemistry and Its Applications LA English DT Editorial Material; Book Chapter ID CHROMATOGRAPHY-MASS SPECTROMETRY; PRESSURIZED LIQUID EXTRACTION; PESTICIDE-RESIDUES; FOOD ANALYSIS; MICROEXTRACTION; MATRICES; MELAMINE; SAFETY; MS C1 [Zhou, Wanlong; Wang, Perry G.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Chang, Eugene Y.] US FDA, Pacific Reg Lab Southwest, Irvine, CA USA. RP Zhou, WL (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 45 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0069-2883 BN 978-1-118-90792-4; 978-1-118-39630-8 J9 CHEM ANAL SERIES MON PY 2014 VL 179 BP 1 EP 14 D2 10.1002/9781118907924 PG 14 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA BD5EU UT WOS:000361370700002 ER PT S AU Wang, PG Vitha, M Kay, J AF Wang, Perry G. Vitha, Mark Kay, Jack BE Wang, PG Vitha, MF Kay, JF TI CHEMICAL ANALYSIS A SERIES OF MONOGRAPHS ON ANALYTICAL CHEMISTRY AND ITS APPLICATIONS PREFACE SO HIGH-THROUGHPUT ANALYSIS FOR FOOD SAFETY SE Chemical Analysis-A Series of Monographs on Analytical Chemistry and Its Applications LA English DT Editorial Material; Book Chapter C1 [Wang, Perry G.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Vitha, Mark] Drake Univ, Des Moines, IA 50311 USA. [Kay, Jack] Univ Strathclyde, Glasgow, Lanark, Scotland. RP Wang, PG (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0069-2883 BN 978-1-118-90792-4; 978-1-118-39630-8 J9 CHEM ANAL SERIES MON PY 2014 VL 179 BP XI EP XII D2 10.1002/9781118907924 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA BD5EU UT WOS:000361370700001 ER PT S AU Vaclavik, L Cajka, T Zhou, WL Wang, PG AF Vaclavik, Lukas Cajka, Tomas Zhou, Wanlong Wang, Perry G. BE Wang, PG Vitha, MF Kay, JF TI SURVEY OF MASS SPECTROMETRY-BASED HIGH-THROUGHPUT METHODS IN FOOD ANALYSIS SO HIGH-THROUGHPUT ANALYSIS FOR FOOD SAFETY SE Chemical Analysis-A Series of Monographs on Analytical Chemistry and Its Applications LA English DT Article; Book Chapter ID TIME-OF-FLIGHT; DESORPTION ELECTROSPRAY-IONIZATION; FAST GAS-CHROMATOGRAPHY; ATMOSPHERIC-PRESSURE PHOTOIONIZATION; SOLID-PHASE MICROEXTRACTION; MULTIPLE PESTICIDE-RESIDUES; HYDROPHILIC-INTERACTION CHROMATOGRAPHY; PERFORMANCE LIQUID-CHROMATOGRAPHY; POLYBROMINATED DIPHENYL ETHERS; EMPLOYING DIRECT ANALYSIS C1 [Vaclavik, Lukas; Zhou, Wanlong; Wang, Perry G.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Cajka, Tomas] Univ Calif Davis, UC Davis Genome Ctr Metabol, Davis, CA 95616 USA. RP Vaclavik, L (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RI Cajka, Tomas/A-8914-2008 OI Cajka, Tomas/0000-0002-9728-3355 NR 146 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0069-2883 BN 978-1-118-90792-4; 978-1-118-39630-8 J9 CHEM ANAL SERIES MON PY 2014 VL 179 BP 15 EP 72 D2 10.1002/9781118907924 PG 58 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA BD5EU UT WOS:000361370700003 ER PT S AU Vaclavikova, M Vaclavik, L Cajka, T AF Vaclavikova, Marta Vaclavik, Lukas Cajka, Tomas BE Wang, PG Vitha, MF Kay, JF TI HIGH-THROUGHPUT ANALYSIS OF MYCOTOXINS SO HIGH-THROUGHPUT ANALYSIS FOR FOOD SAFETY SE Chemical Analysis-A Series of Monographs on Analytical Chemistry and Its Applications LA English DT Article; Book Chapter ID TANDEM MASS-SPECTROMETRY; ION-MOBILITY SPECTROMETRY; SURFACE-PLASMON RESONANCE; LATERAL FLOW IMMUNOASSAY; MULTIPLE MYCOTOXINS; MASKED MYCOTOXINS; LC-MS/MS; EXTRACTION PROCEDURE; BIOLOGICAL MATRICES; MULTIANALYTE METHOD C1 [Vaclavikova, Marta; Vaclavik, Lukas] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Cajka, Tomas] Univ Calif Davis, UC Davis Genome Ctr Metabol, Davis, CA 95616 USA. RP Vaclavikova, M (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RI Cajka, Tomas/A-8914-2008 OI Cajka, Tomas/0000-0002-9728-3355 NR 96 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0069-2883 BN 978-1-118-90792-4; 978-1-118-39630-8 J9 CHEM ANAL SERIES MON PY 2014 VL 179 BP 231 EP 266 D2 10.1002/9781118907924 PG 36 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA BD5EU UT WOS:000361370700009 ER PT B AU Setty, MKHG Hewlett, IK AF Setty, Mohan Kumar Haleyur Giri Hewlett, Indira K. BE Liu, D TI Human Immunodeficiency Virus SO MANUAL OF SECURITY SENSITIVE MICROBES AND TOXINS LA English DT Article; Book Chapter ID REVERSE-TRANSCRIPTASE INHIBITORS; COLONY-STIMULATING FACTOR; DEFICIENCY SYNDROME AIDS; HIV-INFECTED PATIENTS; COMBINED P24 ANTIGEN; TYPE-1 GROUP-O; IN-VITRO; PREEXPOSURE PROPHYLAXIS; ANTIBODY-ASSAYS; NUCLEAR IMPORT C1 [Setty, Mohan Kumar Haleyur Giri; Hewlett, Indira K.] US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Setty, MKHG (reprint author), US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 122 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 978-1-4665-5398-9; 978-1-4665-5396-5 PY 2014 BP 107 EP 122 D2 10.1201/b16752 PG 16 WC Infectious Diseases; Microbiology; Toxicology SC Infectious Diseases; Microbiology; Toxicology GA BD7GW UT WOS:000363061700011 ER PT B AU Schneider, KR Fatica, MK Lampel, KA Warren, BR AF Schneider, K. R. Fatica, M. K. Lampel, K. A. Warren, B. R. BE Liu, D TI Shigella SO MANUAL OF SECURITY SENSITIVE MICROBES AND TOXINS LA English DT Article; Book Chapter ID ACTIN-BASED MOTILITY; ENTEROINVASIVE ESCHERICHIA-COLI; LINKED-IMMUNOSORBENT-ASSAY; SHIGA TOXIN; FLEXNERI 2A; UNIPOLAR LOCALIZATION; SONNEI INFECTION; UNITED-STATES; FOODBORNE OUTBREAK; AEROBACTIN GENES C1 [Schneider, K. R.; Fatica, M. K.] Univ Florida, Dept Food Sci & Human Nutr, Gainesville, FL 32611 USA. [Lampel, K. A.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Warren, B. R.] Land OLakes Inc, Arden Hills, MN USA. RP Schneider, KR (reprint author), Univ Florida, Dept Food Sci & Human Nutr, Gainesville, FL 32611 USA. NR 135 TC 0 Z9 0 U1 1 U2 1 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-5398-9; 978-1-4665-5396-5 PY 2014 BP 385 EP 396 D2 10.1201/b16752 PG 12 WC Infectious Diseases; Microbiology; Toxicology SC Infectious Diseases; Microbiology; Toxicology GA BD7GW UT WOS:000363061700035 ER PT B AU Liu, DY Garber, EAE AF Liu, Dongyou Garber, Eric A. E. BE Liu, D TI Abrin SO MANUAL OF SECURITY SENSITIVE MICROBES AND TOXINS LA English DT Article; Book Chapter ID TOXIC LECTINS ABRIN; ACUTE DEMYELINATING ENCEPHALITIS; RIBOSOME-INACTIVATING PROTEIN; ABRUS-PRECATORIUS AGGLUTININ; LINKED-IMMUNOSORBENT-ASSAY; LEUKEMIC-CELL LINES; A-CHAIN; ESCHERICHIA-COLI; IN-VITRO; X-RAY C1 [Liu, Dongyou] Royal Coll Pathologists Australasia, Biosecur Qual Assurance Program, St Leonards, NSW, Australia. [Garber, Eric A. E.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Liu, DY (reprint author), Royal Coll Pathologists Australasia, Biosecur Qual Assurance Program, St Leonards, NSW, Australia. NR 93 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 978-1-4665-5398-9; 978-1-4665-5396-5 PY 2014 BP 443 EP 450 D2 10.1201/b16752 PG 8 WC Infectious Diseases; Microbiology; Toxicology SC Infectious Diseases; Microbiology; Toxicology GA BD7GW UT WOS:000363061700040 ER PT S AU Chakravarty, AG AF Chakravarty, Aloka G. BE Carini, C Menon, S Chang, M TI Regulatory Issues in Use of Biomarkers in Drug Development SO CLINICAL AND STATISTICAL CONSIDERATIONS IN PERSONALIZED MEDICINE SE Chapman & Hall-CRC Biostatistics Series LA English DT Article; Book Chapter ID CLINICAL-TRIALS; SURROGATE ENDPOINTS; ONCOLOGY TRIALS; END-POINTS; CRITERIA; MARKERS C1 US FDA, Div Biometr 7, Off Biostat, CDER, Silver Spring, MD 20993 USA. RP Chakravarty, AG (reprint author), US FDA, Div Biometr 7, Off Biostat, CDER, Silver Spring, MD 20993 USA. NR 19 TC 2 Z9 2 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 SN 2154-4298 BN 978-1-4665-9387-9 J9 CH CRC BIOSTAT SER JI Chapman & Hall-CRC Biostat. Ser. PY 2014 BP 313 EP 331 PG 19 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA BD6GP UT WOS:000362204000012 ER PT B AU Lee, SC Zhang, L Huang, SM AF Lee, Sue-Chih Zhang, Lei Huang, Shiew-Mei BE You, G Morris, ME TI REGULATORY SCIENCE PERSPECTIVES ON TRANSPORTER STUDIES IN DRUG DEVELOPMENT SO DRUG TRANSPORTERS: MOLECULAR CHARACTERIZATION AND ROLE IN DRUG DISPOSITION, 2ND EDITION SE Wiley Series in Drug Discovery and Development LA English DT Article; Book Chapter ID SALT EXPORT PUMP; ORGANIC CATION TRANSPORTERS; PHARMACOKINETIC INTERACTION; CLINICAL PHARMACOKINETICS; INTRAHEPATIC CHOLESTASIS; EFFLUX TRANSPORTERS; HEALTHY-VOLUNTEERS; TUBULAR SECRETION; RENAL CLEARANCE; LIVER-INJURY C1 [Lee, Sue-Chih; Zhang, Lei; Huang, Shiew-Mei] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Lee, SC (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 89 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, W SUSSEX PO 19 8SQ, ENGLAND BN 978-1-118-70530-8; 978-1-118-48993-2 J9 WILEY SER DRUG DISC PY 2014 BP 473 EP 490 D2 10.1002/9781118705308 PG 18 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BD6BR UT WOS:000362007500025 ER PT S AU Rahman, Z Siddiqui, A Gupta, A Khan, M AF Rahman, Ziyaur Siddiqui, Akhtar Gupta, Abhay Khan, Mansoor BE Shah, N Sandhu, H Choi, DS Chokshi, H Malick, AW TI Regulatory Considerations in Development of Amorphous Solid Dispersions SO AMORPHOUS SOLID DISPERSIONS: THEORY AND PRACTICE SE Advances in Delivery Science and Technology LA English DT Article; Book Chapter ID GLASS-TRANSITION TEMPERATURE; WATER-SOLUBLE DRUGS; HOT-MELT EXTRUSION; PHYSICAL STABILITY; PHARMACEUTICAL SOLIDS; SOLVENT EVAPORATION; DIFFERENT POLYMERS; DISSOLUTION RATE; BINARY-SYSTEMS; PART I C1 [Rahman, Ziyaur; Siddiqui, Akhtar; Gupta, Abhay; Khan, Mansoor] US FDA, Div Prod Qual & Res, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Khan, M (reprint author), US FDA, Div Prod Qual & Res, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. EM Mansoor.Khan@fda.hhs.gov OI Rahman, Ziyaur/0000-0002-0402-825X NR 92 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2192-6204 BN 978-1-4939-1598-9; 978-1-4939-1597-2 J9 ADV DEL SCI TECHNOL PY 2014 BP 545 EP 563 DI 10.1007/978-1-4939-1598-9_17 D2 10.1007/978-1-4939-1598-9 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BD2LH UT WOS:000358864000018 ER PT B AU Dibaji, SAR Myers, MR Soneson, JE Banerjee, RK AF Dibaji, Seyed Ahmad Reza Myers, Matthew R. Soneson, Joshua E. Banerjee, Rupak K. GP ASME TI NONLINEAR DERATING OF HIGH-INTENSITY THERAPEUTIC ULTRASOUND BEAMS USING GAUSSIAN MODAL SUMS SO PROCEEDINGS OF THE ASME SUMMER BIOENGINEERING CONFERENCE - 2013, PT A LA English DT Proceedings Paper CT 15th American-Society-Mechanical-Engineering Summer Bioengineering Conference (SBC2013) CY JUN 26-29, 2013 CL Sunriver, OR SP Amer Soc Mech Engn, Bioengineer Div C1 [Dibaji, Seyed Ahmad Reza; Banerjee, Rupak K.] Univ Cincinnati, Sch Dynam Syst, Mech Engn Program, Cincinnati, OH 45221 USA. [Myers, Matthew R.; Soneson, Joshua E.] US FDA, Ctr Devices & Radiol Hlth, Div Solid & Fluid Mech, Silver Spring, MD USA. RP Dibaji, SAR (reprint author), Univ Cincinnati, Sch Dynam Syst, Mech Engn Program, Cincinnati, OH 45221 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-5560-7 PY 2014 AR V01AT07A014 PG 2 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA BD2YH UT WOS:000359389200093 ER PT B AU Vesnovsky, O Topoleski, LDT Grossman, LW Casamento, JP Zhu, L AF Vesnovsky, Oleg Topoleski, L. D. Timmie Grossman, Laurence W. Casamento, Jon P. Zhu, Liang GP ASME TI EVALUATION OF TEMPERATURE TRANSIENTS AT VARIOUS BODY TEMPERATURE MEASURING SITES USING A FAST RESPONSE THERMISTOR BEAD SENSOR SO PROCEEDINGS OF THE ASME SUMMER BIOENGINEERING CONFERENCE - 2013, PT A LA English DT Proceedings Paper CT 15th American-Society-Mechanical-Engineering Summer Bioengineering Conference (SBC2013) CY JUN 26-29, 2013 CL Sunriver, OR SP Amer Soc Mech Engn, Bioengineer Div ID THERMOMETER; ACCURACY C1 [Vesnovsky, Oleg; Topoleski, L. D. Timmie; Grossman, Laurence W.; Casamento, Jon P.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Topoleski, L. D. Timmie; Zhu, Liang] Univ Maryland Baltimore Cty, Dept Mech Engn, Baltimore, MD 21250 USA. RP Vesnovsky, O (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-5560-7 PY 2014 AR V01AT07A003 PG 2 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA BD2YH UT WOS:000359389200082 ER PT B AU Walsh, D Stephen, B Duraiswamy, N Vesnovsky, O Topoleski, LDT AF Walsh, Donna Stephen, Beth Duraiswamy, Nandini Vesnovsky, Oleg Topoleski, L. D. Timmie GP ASME TI PARAMETERS INFLUENCING DISTAL TIP LOADING OF PACEMAKER AND DEFIBRILLATOR LEADS SO PROCEEDINGS OF THE ASME SUMMER BIOENGINEERING CONFERENCE - 2013, PT A LA English DT Proceedings Paper CT 15th American-Society-Mechanical-Engineering Summer Bioengineering Conference (SBC2013) CY JUN 26-29, 2013 CL Sunriver, OR SP Amer Soc Mech Engn, Bioengineer Div C1 [Walsh, Donna; Stephen, Beth; Duraiswamy, Nandini; Vesnovsky, Oleg; Topoleski, L. D. Timmie] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Topoleski, L. D. Timmie] Univ Maryland, Dept Mech Engn, Baltimore, MD 21250 USA. RP Walsh, D (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-5560-7 PY 2014 AR V01AT20A008 PG 2 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA BD2YH UT WOS:000359389200252 ER PT B AU Myers, MR Hariharan, P Banerjee, RK AF Myers, Matthew R. Hariharan, Prasanna Banerjee, Rupak K. GP ASME TI TRANSLATIONAL RESEARCH IN HIGH-INTENSITY THERAPEUTIC ULTRASOUND: NOVEL TECHNIQUES FOR PRE-CLINICAL TESTING SO PROCEEDINGS OF THE ASME SUMMER BIOENGINEERING CONFERENCE - 2013, PT B LA English DT Proceedings Paper CT 15th American-Society-Mechanical-Engineering Summer Bioengineering Conference (SBC2013) CY JUN 26-29, 2013 CL Sunriver, OR SP Amer Soc Mech Engn, Bioengineer Div ID INFRARED THERMOGRAPHY C1 [Myers, Matthew R.; Hariharan, Prasanna] US FDA, Ctr Devices & Radiol Hlth, Div Solid & Fluid Mech, Silver Spring, MD 20993 USA. [Banerjee, Rupak K.] Univ Cincinnati, Dept Mech Engn, Cincinnati, OH 45221 USA. [Banerjee, Rupak K.] Univ Cincinnati, Biomed Engn Dept, Cincinnati, OH 45221 USA. RP Myers, MR (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Solid & Fluid Mech, Silver Spring, MD 20993 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-5561-4 PY 2014 AR V01BT53A003 PG 2 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA BD2YI UT WOS:000359389300181 ER PT B AU Sahu, SC Casciano, DA AF Sahu, Saura C. Casciano, Daniel A. BE Sahu, SC Casciano, DA TI Handbook of Nanotoxicology, Nanomedicine and Stem Cell Use in Toxicology Preface SO HANDBOOK OF NANOTOXICOLOGY, NANOMEDICINE AND STEM CELL USE IN TOXICOLOGY LA English DT Editorial Material; Book Chapter C1 [Sahu, Saura C.] US FDA, Laurel, MD 20993 USA. [Casciano, Daniel A.] Univ Arkansas, Little Rock, AR 72204 USA. RP Sahu, SC (reprint author), US FDA, Laurel, MD 20993 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, W SUSSEX PO 19 8SQ, ENGLAND BN 978-1-118-85604-8; 978-1-118-43926-5 PY 2014 BP XI EP XI D2 10.1002/9781118856017 PG 1 WC Cell Biology; Nanoscience & Nanotechnology; Toxicology SC Cell Biology; Science & Technology - Other Topics; Toxicology GA BD0PW UT WOS:000357535600001 ER PT B AU Keene, AM Bancos, S Tyner, KM AF Keene, Athena M. Bancos, Simona Tyner, Katherine M. BE Sahu, SC Casciano, DA TI Considerations for In Vitro Nanotoxicity Testing SO HANDBOOK OF NANOTOXICOLOGY, NANOMEDICINE AND STEM CELL USE IN TOXICOLOGY LA English DT Article; Book Chapter ID WALLED CARBON NANOTUBES; SOLID LIPID NANOPARTICLES; A549 LUNG-CELLS; GOLD NANOPARTICLES; SILICA NANOPARTICLES; ENGINEERED NANOMATERIALS; TOXICITY ASSESSMENT; VIABILITY ASSAYS; VIBRIO-FISCHERI; CELLULAR UPTAKE C1 [Keene, Athena M.] Afton Chem Corp, Richmond, VA 23219 USA. [Bancos, Simona; Tyner, Katherine M.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Keene, AM (reprint author), Afton Chem Corp, Richmond, VA 23219 USA. NR 113 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, W SUSSEX PO 19 8SQ, ENGLAND BN 978-1-118-85604-8; 978-1-118-43926-5 PY 2014 BP 35 EP 63 D2 10.1002/9781118856017 PG 29 WC Cell Biology; Nanoscience & Nanotechnology; Toxicology SC Cell Biology; Science & Technology - Other Topics; Toxicology GA BD0PW UT WOS:000357535600003 ER PT B AU Li, Y Chen, T AF Li, Yan Chen, Tao BE Sahu, SC Casciano, DA TI Genotoxicity of Silver Nanoparticles SO HANDBOOK OF NANOTOXICOLOGY, NANOMEDICINE AND STEM CELL USE IN TOXICOLOGY LA English DT Article; Book Chapter ID IN-VITRO; OXIDATIVE STRESS; DNA-DAMAGE; DEPENDENT GENERATION; NEREIS-DIVERSICOLOR; CELLULAR TOXICITY; NANO-SILVER; CELLS; NANOMATERIALS; CYTOTOXICITY C1 [Li, Yan; Chen, Tao] US FDA, Div Genet & Mol Toxicol, NCTR, Jefferson, AR 72079 USA. RP Li, Y (reprint author), US FDA, Div Genet & Mol Toxicol, NCTR, Jefferson, AR 72079 USA. NR 74 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, W SUSSEX PO 19 8SQ, ENGLAND BN 978-1-118-85604-8; 978-1-118-43926-5 PY 2014 BP 87 EP 98 D2 10.1002/9781118856017 PG 12 WC Cell Biology; Nanoscience & Nanotechnology; Toxicology SC Cell Biology; Science & Technology - Other Topics; Toxicology GA BD0PW UT WOS:000357535600005 ER PT B AU Inselman, AL Wang, C Liu, F Hansen, DK AF Inselman, Amy L. Wang, Cheng Liu, Fang Hansen, Deborah K. BE Sahu, SC Casciano, DA TI Stem Cells in Toxicity Testing SO HANDBOOK OF NANOTOXICOLOGY, NANOMEDICINE AND STEM CELL USE IN TOXICOLOGY LA English DT Article; Book Chapter ID VITRO EMBRYOTOXICITY TESTS; WHOLE-EMBRYO CULTURE; END-POINT ANALYSIS; IN-VITRO; DEVELOPMENTAL TOXICITY; GENE-EXPRESSION; MOLECULAR MARKERS; TEST EST; NEURAL DIFFERENTIATION; RESPONSE EVALUATION C1 [Inselman, Amy L.; Hansen, Deborah K.] US FDA, Div Syst Biol, NCTR, Jefferson, AR 72079 USA. [Wang, Cheng; Liu, Fang] US FDA, Div Neurotoxicol, NCTR, Jefferson, AR USA. RP Inselman, AL (reprint author), US FDA, Div Syst Biol, NCTR, Jefferson, AR 72079 USA. NR 94 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, W SUSSEX PO 19 8SQ, ENGLAND BN 978-1-118-85604-8; 978-1-118-43926-5 PY 2014 BP 251 EP 265 D2 10.1002/9781118856017 PG 15 WC Cell Biology; Nanoscience & Nanotechnology; Toxicology SC Cell Biology; Science & Technology - Other Topics; Toxicology GA BD0PW UT WOS:000357535600015 ER PT B AU Young, RR Powley, M Lawlor, TE Aardema, MJ AF Young, Robert R. Powley, Mark Lawlor, Timothy E. Aardema, Marilyn J. BE Brock, WJ TI GENETIC TOXICOLOGY STUDIES SO ROLE OF THE STUDY DIRECTOR IN NONCLINICAL STUDIES: PHARMACEUTICALS, CHEMICALS, MEDICAL DEVICES, AND PESTICIDES LA English DT Article; Book Chapter ID CHINESE-HAMSTER OVARY; MOUSE LYMPHOMA-CELLS; ERYTHROCYTE MICRONUCLEUS ASSAY; FLOW-CYTOMETRIC ANALYSIS; THYMIDINE KINASE GENE; DNA-REPAIR ASSAY; IN-VITRO; COMET ASSAY; MUTATION ASSAY; PIG-A C1 [Young, Robert R.; Lawlor, Timothy E.] BioReliance Corp, Rockville, MD 20850 USA. [Powley, Mark] US FDA, CDER, Silver Spring, MD USA. [Aardema, Marilyn J.] Marilyn Aardema Consulting LLC, Fairfield, OH USA. [Aardema, Marilyn J.] BioReliance Corp, Fairfield, OH USA. RP Young, RR (reprint author), BioReliance Corp, Rockville, MD 20850 USA. NR 94 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-87390-8; 978-1-118-37039-1 PY 2014 BP 333 EP 354 D2 10.1002/9781118873922 PG 22 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BC7LO UT WOS:000354987000021 ER PT B AU Taylor, DR AF Taylor, Deborah R. BE Fox, JG Marini, RP TI The Ferret in Viral Respiratory Disease Research SO BIOLOGY AND DISEASES OF THE FERRET, 3RD EDITION LA English DT Article; Book Chapter ID ANTIBODY-DEPENDENT ENHANCEMENT; FELINE INFECTIOUS PERITONITIS; INFLUENZA-A VIRUS; SYNDROME CORONAVIRUS; PANDEMIC INFLUENZA; LYMPHOCYTE SUBSETS; SYNCYTIAL VIRUS; H5N1 VIRUSES; SARS; TRANSMISSION C1 CBER FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review, Bethesda, MD 20993 USA. RP Taylor, DR (reprint author), CBER FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review, Bethesda, MD 20993 USA. NR 62 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-78269-9; 978-0-470-96045-5 PY 2014 BP 629 EP 639 D2 10.1002/9781118782699 PG 11 WC Veterinary Sciences SC Veterinary Sciences GA BC7IT UT WOS:000354901200026 ER PT B AU Rabin, RL Slater, JE AF Rabin, Ronald L. Slater, Jay E. BE Lockey, RF Ledford, DK TI Standardized Allergen Vaccines in the United States SO ALLERGENS AND ALLERGEN IMMUNOTHERAPY: SUBCUTANEOUS, SUBLINGUAL,AND ORAL, 5TH EDITION LA English DT Article; Book Chapter ID COMPOSITIONAL DIFFERENCES CD; CAT EXTRACTS SCE; POTENCY; ASSIGNMENT; STABILITY; PRODUCTS; GERMAN; AU C1 [Rabin, Ronald L.] US FDA, Div Bacterial Parasit & Allergen Prod, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Slater, Jay E.] US FDA, Lab Immunobiochem, Div Bacterial Parasit & Allergen Prod, Off Vaccines Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Rabin, RL (reprint author), US FDA, Div Bacterial Parasit & Allergen Prod, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 33 TC 3 Z9 3 U1 1 U2 1 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-84214-574-6; 978-1-84214-573-9 PY 2014 BP 281 EP 287 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA BC3RG UT WOS:000351872300021 ER PT S AU Barrett, HH Myers, KJ Caucci, L AF Barrett, Harrison H. Myers, Kyle J. Caucci, Luca BE Gregory, GG Davis, AJ TI RADIANCE AND PHOTON NOISE: Imaging in geometrical optics, physical optics, quantum optics and radiology SO NOVEL OPTICAL SYSTEMS DESIGN AND OPTIMIZATION XVII SE Proceedings of SPIE LA English DT Proceedings Paper CT 17th Conference of Novel Optical Systems Design and Optimization CY AUG 17-19, 2014 CL San Diego, CA SP SPIE DE Radiance; geometrical optics; physical optics; quantum imaging; radiology; point processes; image; quality ID NEUMANN-SERIES APPROACH; LIST-MODE LIKELIHOOD; OBJECTIVE ASSESSMENT; QUALITY; RADIOMETRY; COHERENCE; DETECTORS; TRANSPORT; ALGORITHM; MEDIA AB A fundamental way of describing a photon-limited imaging system is in terms of a Poisson random process in spatial, angular and wavelength variables. The mean of this random process is the spectral radiance. The principle of conservation of radiance then allows a full characterization of the noise in the image (conditional on viewing a specified object). To elucidate these connections, we first review the definitions and basic properties of radiance as defined in terms of geometrical optics, radiology, physical optics and quantum optics. The propagation and conservation laws for radiance in each of these domains are reviewed. Then 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. The relation between the radiance and the statistical properties of the detector output is discussed and related to task-based measures of image quality and the information content of a single detected photon. C1 [Barrett, Harrison H.] Univ Arizona, Coll Opt Sci, Tucson, AZ 85721 USA. [Barrett, Harrison H.; Caucci, Luca] Ctr Gamma Ray Imaging, Dept Med Imaging, Tucson, AZ 85724 USA. [Myers, Kyle J.] US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, Silver Spring, MD 20993 USA. RP Barrett, HH (reprint author), Arizona Hlth Sci Ctr, Ctr Gamma Ray Imaging, Radiol Res Lab, Tucson, AZ 85724 USA. EM barrett@radiology.arizona.edu NR 25 TC 2 Z9 2 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 978-1-62841-220-8 J9 PROC SPIE PY 2014 VL 9193 AR 919302 DI 10.1117/12.2066715 PG 17 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BC6PX UT WOS:000354367700001 ER PT S AU Pillai, KV Hunt, PR Duncan, TV AF Pillai, Karthik V. Hunt, Piper R. Duncan, Timothy V. BE Snedeker, SM TI Nanoparticles in Polymer Nanocomposite Food Contact Materials: Uses, Potential Release, and Emerging Toxicological Concerns SO TOXICANTS IN FOOD PACKAGING AND HOUSEHOLD PLASTICS: EXPOSURE AND HEALTH RISKS TO CONSUMERS SE Molecular and Integrative Toxicology LA English DT Article; Book Chapter DE Engineered nanomaterials; Food packaging; Polymer nanocomposites; Migration; Nanotoxicity; Nanoparticle toxicity; Safety of nanotechnology ID ZINC-OXIDE NANOPARTICLES; SPRAGUE-DAWLEY RATS; SILVER NANOPARTICLES; ORAL TOXICITY; ENGINEERED NANOMATERIALS; DIOXIDE NANOPARTICLES; TITANIUM-DIOXIDE; HIGH-PRESSURE; IN-VITRO; MIGRATION AB Several types of nanotechnology-enabled plastics intended for the storage and transport of foods are close to commercialization. For food contact applications, nanocomposite plastics offer many advantages over traditional polymers. However, while the unique properties of engineered nanomaterials (ENMs) may be harnessed for many positive ends, there are concerns about whether ENMs pose risks to human health. The primary areas of interest for assessing safety of nanocomposite food contact materials (FCM) are the potential for migration of ENMs into food and the potential toxicity of such released ENMs. This chapter offers a review of theoretical and experimental methods to assess the likelihood of ENM release from nanotechnology-enabled materials into liquid media, as well as a brief overview of the potential toxicological considerations of ENMs likely to be used in FCMs. Because the use of nanotechnology in food contact applications is a developing field, this chapter also provides background information on some of the food-related applications of nanocomposites currently in development, and a discussion of current methods being used to assess the release of non-nanoscale food packaging additives or contaminants. The goal of this work is to provide readers with an appreciation for current activity in this field as well as an understanding of data gaps that may need to be addressed in order to ensure the safety of this emerging technology. C1 [Pillai, Karthik V.; Duncan, Timothy V.] US FDA, Div Food Proc Sci & Technol, Off Food Safety, Ctr Food Safety & Appl Nutr, Bedford Pk, IL 60501 USA. [Hunt, Piper R.] US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD USA. RP Duncan, TV (reprint author), US FDA, Div Food Proc Sci & Technol, Off Food Safety, Ctr Food Safety & Appl Nutr, Bedford Pk, IL 60501 USA. EM Karthik.Pillai@fda.hhs.gov; Piper.Hunt@fda.hhs.gov; timothy.duncan@fda.hhs.gov RI Hunt, Piper/G-1555-2012 OI Hunt, Piper/0000-0003-0538-7606 NR 86 TC 1 Z9 1 U1 3 U2 11 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY, ENGLAND SN 2168-4219 BN 978-1-4471-6500-2; 978-1-4471-6499-9 J9 MOLEC INTEGR TOXICOL PY 2014 BP 95 EP 123 DI 10.1007/978-1-4471-6500-2_4 D2 10.1007/978-1-4471-6500-2 PG 29 WC Environmental Sciences; Food Science & Technology; Toxicology SC Environmental Sciences & Ecology; Food Science & Technology; Toxicology GA BC6BJ UT WOS:000353720200005 ER PT S AU Rice, PA Bandele, OJ Honigfort, P AF Rice, Penelope A. Bandele, Omari J. Honigfort, Paul BE Snedeker, SM TI Perfluorinated Compounds in Food Contact Materials SO TOXICANTS IN FOOD PACKAGING AND HOUSEHOLD PLASTICS: EXPOSURE AND HEALTH RISKS TO CONSUMERS SE Molecular and Integrative Toxicology LA English DT Article; Book Chapter DE Perfluorinated; Fluorotelomer; PFOA; Perfluoroalkyl; Perfluorooctanoic; Perfluorononanoic; Perfluorodecanoic; Perfluorododecanoic; Perfluorooctylethanol; FTOH; Perfluorocarboxylates; Food packaging ID ACTIVATED RECEPTOR-ALPHA; PERFLUOROOCTANE SULFONATE PFOS; MAMMARY-GLAND DEVELOPMENT; 8-2 FLUOROTELOMER ALCOHOL; HUMAN SEMEN QUALITY; FLUOROCHEMICAL PRODUCTION WORKERS; RESTRICTED GESTATIONAL EXPOSURES; PEROXISOMAL BETA-OXIDATION; NATIONAL BIRTH COHORT; SPRAGUE-DAWLEY RATS AB Perfluorinated compounds (PFCs) exhibit unique physical characteristics including hydrophobic and oleophobic properties as well as thermal and chemical stability. Due to these characteristics, PFCs are used in a wide variety of industrial and consumer applications, including automotive, electrical, clothing, and household products. PFCs are ubiquitous in the environment and PFCs greater than seven carbons in length have been found to bioaccumulate in wildlife and humans. Furthermore, laboratory animal studies have raised concerns as to the safety of human exposure to these compounds. Although their use in the manufacture of food contact substances (FCSs) constitutes a small segment of the use of PFCs, their use in food packaging and migration to foodstuffs does represent a potential source of oral exposure to humans. This chapter focuses on aspects of human exposure, and potential health risks associated with two types of long-chain PFCs that historically have been found in food packaging: perfluorinated carboxylic acids (PFCAs) and fluorinated telomer alcohols (FTOHs). C1 [Rice, Penelope A.; Bandele, Omari J.; Honigfort, Paul] US FDA, Div Food Contact Notificat, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 20993 USA. RP Rice, PA (reprint author), US FDA, Div Food Contact Notificat, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 20993 USA. EM Penelope.Rice@fda.hhs.gov; Omari.Bandele@fda.hhs.gov; Paul.Honigfort@fda.hhs.gov NR 164 TC 0 Z9 0 U1 2 U2 10 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY, ENGLAND SN 2168-4219 BN 978-1-4471-6500-2; 978-1-4471-6499-9 J9 MOLEC INTEGR TOXICOL PY 2014 BP 177 EP 203 DI 10.1007/978-1-4471-6500-2_7 D2 10.1007/978-1-4471-6500-2 PG 27 WC Environmental Sciences; Food Science & Technology; Toxicology SC Environmental Sciences & Ecology; Food Science & Technology; Toxicology GA BC6BJ UT WOS:000353720200008 ER PT J AU Wear, K Nagatani, Y Mizuno, K Matsukawa, M AF Wear, Keith Nagatani, Yoshiki Mizuno, Katsunori Matsukawa, Mami GP IEEE TI Temporal Evolution of Fast and Slow Waves During Propagation Through Bovine Cancellous Bone In Vitro SO 2014 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS) LA English DT Proceedings Paper CT IEEE International Ultrasonics Symposium (IUS) CY SEP 03-06, 2014 CL Chicago, IL SP IEEE DE fast and slow waves; cancellous bone ID BAND ULTRASOUND ATTENUATION; PHASE CANCELLATION; TRABECULAR BONE; STRUCTURAL ANISOTROPY; GROUP-VELOCITY; SIMULATION; DISPERSION; PHANTOM; FEMUR; SPEED AB Fast and slow waves were detected in a bovine cancellous bone sample for thicknesses ranging from 7 to 12 mm using bandlimited deconvolution and the modified least-squares Prony's method with curve fitting (MLSP+CF). Bandlimited deconvolution consistently isolated two waves with linear-with-frequency attenuation coefficients, as evidenced by high correlation coefficients between attenuation coefficient and frequency: 0.997 +/- 0.002 (fast wave) and 0.986 +/- 0.013 (slow wave) (mean +/- standard deviation). Average root-mean-squared (RMS) differences between the two algorithms for phase velocities were 5 m/s (fast wave, 350 kHz) and 13 m/s (slow wave, 750 kHz). Average RMS differences for signal loss were 1.6 dB (fast wave, 350 kHz) and 0.4 dB (slow wave, 750 kHz). Phase velocities for thickness = 10 mm were 1726 m/s (fast wave, 350 kHz) and 1455 m/s (slow wave, 750 kHz). Results show support for the model of two waves with linear-with frequency attenuation, successful isolation of fast and slow waves, good agreement between bandlimited deconvolution and MLSP+CF as well as with a Bayesian algorithm, and potential variations of fast and/or slow wave properties with bone sample thickness. C1 [Wear, Keith] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Nagatani, Yoshiki] Kobe City Coll Technol, Dept Elect, Kobe, Hyogo, Japan. [Mizuno, Katsunori] Univ Tokyo, Inst Ind Sci, Underwater Technol Collaborat Res Ctr, Tokyo, Japan. [Matsukawa, Mami] Doshisha Univ, Fac Sci & Engn, Lab Ultrason Elect, Kyoto 602, Japan. RP Wear, K (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-7049-0 PY 2014 BP 927 EP 930 DI 10.1109/ULTSYM.2014.0227 PG 4 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BC4NN UT WOS:000352792500226 ER PT J AU Wear, KA Maruvada, S Liu, YB Harris, GR Gammell, P AF Wear, Keith A. Maruvada, Subha Liu, Yunbo Harris, Gerald R. Gammell, Paul GP IEEE TI Suppression of Pressure Measurement Artifacts from Fiber Optic Hydrophones Using Complex Deconvolution of Sensitivity SO 2014 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS) LA English DT Proceedings Paper CT IEEE International Ultrasonics Symposium (IUS) CY SEP 03-06, 2014 CL Chicago, IL SP IEEE DE hydrophones; acoustic output; fiber optic AB Nonlinear acoustic signals contain significant energy at many harmonic frequencies. For many applications, the sensitivity (frequency response) of a hydrophone will not be uniform over such a broad spectrum. In a continuation of a previous investigation involving deconvolution methodology, deconvolution (implemented in the frequency domain as an inverse filter computed from frequency-dependent hydrophone sensitivity) was investigated for improvement of accuracy and precision of nonlinear acoustic output measurements. Time delay spectrometry (TDS) was used to measure complex sensitivities for six fiber-optic hydrophones. The hydrophones were then used to measure a pressure wave with rich harmonic content. Spectral asymmetry between compressional and rarefactional segments was exploited in order to design filters used in conjunction with deconvolution. Complex deconvolution reduced mean bias (for 6 fiber-optic hydrophones) and mean coefficient of variation (COV) for peak compressional pressure (p+), peak rarefactional pressure (p-), and pulse intensity integral (PII). Deconvolution based on sensitivity magnitude or the minimum phase model also resulted in significant reductions in mean bias and COY of acoustic output parameters but was less effective than direct complex deconvolution for p+ and P-. Therefore, deconvolution with appropriate filtering facilitates reliable nonlinear acoustic output measurements using hydrophones with frequency-dependent sensitivity. C1 [Wear, Keith A.; Maruvada, Subha; Liu, Yunbo; Harris, Gerald R.] US FDA, Silver Spring, MD 20993 USA. [Gammell, Paul] Gammell Appl Technol, Exmore, VA USA. RP Wear, KA (reprint author), US FDA, Silver Spring, MD 20993 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-7049-0 PY 2014 BP 1172 EP 1174 DI 10.1109/ULTSYM.2014.0288 PG 3 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BC4NN UT WOS:000352792500287 ER PT S AU Yu, A Sun, DX Li, BV Yu, LX AF Yu, Alex Sun, Duxin Li, Bing V. Yu, Lawrence X. BE Yu, LX Li, BV TI Bioequivalence History SO FDA BIOEQUIVALENCE STANDARDS SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Article; Book Chapter ID DISPOSITION CLASSIFICATION-SYSTEM; HIGHLY VARIABLE DRUGS; INDIVIDUAL BIOEQUIVALENCE; PHYSIOLOGIC AVAILABILITY; TETRACYCLINE PRODUCTS; BIOLOGIC AVAILABILITY; RELEASE FORMULATIONS; INHALER DEVICES; PARTIAL AUC; IN-VITRO C1 [Yu, Alex; Sun, Duxin] Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. [Li, Bing V.; Yu, Lawrence X.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Yu, LX (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire, Silver Spring, MD 20993 USA. EM alexmyu@med.umich.edu; duxins@med.umich.edu; bing.li@fda.hhs.gov; Lawrence.Yu@fda.hhs.gov NR 93 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2210-7371 BN 978-1-4939-1252-0; 978-1-4939-1251-3 J9 AAPS ADV PHARM SCI PY 2014 BP 1 EP 27 DI 10.1007/978-1-4939-1252-0_1 D2 10.1007/978-1-4939-1252-0 PG 27 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BC1TO UT WOS:000350418100003 ER PT S AU Yu, LX Li, BV AF Yu, Lawrence X. Li, Bing V. BE Yu, LX Li, BV TI FDA Bioequivalence Standards Preface SO FDA BIOEQUIVALENCE STANDARDS SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Editorial Material; Book Chapter C1 [Yu, Lawrence X.] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Li, Bing V.] US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Yu, LX (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2210-7371 BN 978-1-4939-1252-0; 978-1-4939-1251-3 J9 AAPS ADV PHARM SCI PY 2014 BP VII EP VIII D2 10.1007/978-1-4939-1252-0 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BC1TO UT WOS:000350418100002 ER PT S AU Chen, ML AF Chen, Mei-Ling BE Yu, LX Li, BV TI Fundamentals of Bioequivalence SO FDA BIOEQUIVALENCE STANDARDS SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Article; Book Chapter ID RELEASE FORMULATIONS; CLINICAL PHARMACOKINETICS; LINEAR PHARMACOKINETICS; IBUPROFEN ENANTIOMERS; SORBITOL INTOLERANCE; DRUG PRODUCTS; METABOLITES; HUMANS; PHARMACODYNAMICS; EQUIVALENCE C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Chen, ML (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM meiling.chen@fda.hhs.gov NR 61 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2210-7371 BN 978-1-4939-1252-0; 978-1-4939-1251-3 J9 AAPS ADV PHARM SCI PY 2014 BP 29 EP 53 DI 10.1007/978-1-4939-1252-0_2 D2 10.1007/978-1-4939-1252-0 PG 25 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BC1TO UT WOS:000350418100004 ER PT S AU Makhlouf, FT Grosser, SC Schuirmann, DJ AF Makhlouf, Fairouz T. Grosser, Stella C. Schuirmann, Donald J. BE Yu, LX Li, BV TI Basic Statistical Considerations SO FDA BIOEQUIVALENCE STANDARDS SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Article; Book Chapter ID INDIVIDUAL BIOEQUIVALENCE; CONFIDENCE-INTERVALS; BIOAVAILABILITY; EQUIVALENCE; DESIGN C1 [Makhlouf, Fairouz T.; Grosser, Stella C.; Schuirmann, Donald J.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Makhlouf, FT (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Fairouz.Makhlouf@fda.hhs.gov NR 19 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2210-7371 BN 978-1-4939-1252-0; 978-1-4939-1251-3 J9 AAPS ADV PHARM SCI PY 2014 BP 55 EP 93 DI 10.1007/978-1-4939-1252-0_3 D2 10.1007/978-1-4939-1252-0 PG 39 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BC1TO UT WOS:000350418100005 ER PT S AU DeHaven, WI Conner, DP AF DeHaven, Wayne I. Conner, Dale P. BE Yu, LX Li, BV TI The Effects of Food on Drug Bioavailability and Bioequivalence SO FDA BIOEQUIVALENCE STANDARDS SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Article; Book Chapter ID GASTROINTESTINAL-TRACT; RELEASE FORMULATIONS; 1ST-PASS METABOLISM; ABSORPTION; PHARMACOKINETICS; TABLETS; PH; DISSOLUTION; NIFEDIPINE; HEALTHY C1 [DeHaven, Wayne I.; Conner, Dale P.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP DeHaven, WI (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Wayne.Dehaven@fda.hhs.gov NR 66 TC 0 Z9 0 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2210-7371 BN 978-1-4939-1252-0; 978-1-4939-1251-3 J9 AAPS ADV PHARM SCI PY 2014 BP 95 EP 118 DI 10.1007/978-1-4939-1252-0_4 D2 10.1007/978-1-4939-1252-0 PG 24 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BC1TO UT WOS:000350418100006 ER PT S AU Uppoor, RS Vaidyanathan, J Mehta, M Yu, LX AF Uppoor, Ramana S. Vaidyanathan, Jayabharathi Mehta, Mehul Yu, Lawrence X. BE Yu, LX Li, BV TI Biowaiver and Biopharmaceutics Classification System SO FDA BIOEQUIVALENCE STANDARDS SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Article; Book Chapter ID ORAL-DRUG ABSORPTION; CLASS-III DRUGS; GASTROINTESTINAL TRANSIT; INTESTINAL TRANSIT; DOSAGE FORMS; BIOAVAILABILITY; BCS; BIOEQUIVALENCE; PERMEABILITY; DISSOLUTION C1 [Uppoor, Ramana S.; Vaidyanathan, Jayabharathi; Mehta, Mehul; Yu, Lawrence X.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Uppoor, RS (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Ramana.Uppoor@fda.hhs.gov NR 41 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2210-7371 BN 978-1-4939-1252-0; 978-1-4939-1251-3 J9 AAPS ADV PHARM SCI PY 2014 BP 119 EP 137 DI 10.1007/978-1-4939-1252-0_5 D2 10.1007/978-1-4939-1252-0 PG 19 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BC1TO UT WOS:000350418100007 ER PT S AU Davit, BM Patel, DT AF Davit, Barbara M. Patel, Devvrat T. BE Yu, LX Li, BV TI Bioequivalence of Highly Variable Drugs SO FDA BIOEQUIVALENCE STANDARDS SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Article; Book Chapter ID SCALED AVERAGE BIOEQUIVALENCE; SIDED TESTS PROCEDURE; PRODUCTS; BIOAVAILABILITY; POWER; FDA C1 [Davit, Barbara M.] Merck Sharp & Dohme Corp, Clin Res, Biopharmaceut, Whitehouse Stn, NJ 08889 USA. [Patel, Devvrat T.] US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20855 USA. RP Davit, BM (reprint author), Merck Sharp & Dohme Corp, Clin Res, Biopharmaceut, One Merck Dr,POB 100, Whitehouse Stn, NJ 08889 USA. EM Barbara.Davit@merck.com NR 40 TC 0 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2210-7371 BN 978-1-4939-1252-0; 978-1-4939-1251-3 J9 AAPS ADV PHARM SCI PY 2014 BP 139 EP 164 DI 10.1007/978-1-4939-1252-0_6 D2 10.1007/978-1-4939-1252-0 PG 26 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BC1TO UT WOS:000350418100008 ER PT S AU Zhu, H Uppoor, RS Mehta, M Yu, LX AF Zhu, Hao Uppoor, Ramana S. Mehta, Mehul Yu, Lawrence X. BE Yu, LX Li, BV TI Partial Area Under the Curve: An Additional Pharmacokinetic Metric for Bioavailability and Bioequivalence Assessments SO FDA BIOEQUIVALENCE STANDARDS SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Article; Book Chapter ID EXTENDED-RELEASE FORMULATIONS; THERAPEUTIC EQUIVALENCE; DRUG ABSORPTION; REGULATORY STANDARDS; PARTIAL AUC; PRODUCTS; OPPORTUNITIES; CHALLENGES; INHIBITOR; EXPOSURE C1 [Zhu, Hao; Uppoor, Ramana S.; Mehta, Mehul; Yu, Lawrence X.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Zhu, H (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Hao.Zhu@fda.hhs.gov NR 49 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2210-7371 BN 978-1-4939-1252-0; 978-1-4939-1251-3 J9 AAPS ADV PHARM SCI PY 2014 BP 165 EP 190 DI 10.1007/978-1-4939-1252-0_7 D2 10.1007/978-1-4939-1252-0 PG 26 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BC1TO UT WOS:000350418100009 ER PT S AU Jiang, WL Yu, LX AF Jiang, Wenlei Yu, Lawrence X. BE Yu, LX Li, BV TI Bioequivalence for Narrow Therapeutic Index Drugs SO FDA BIOEQUIVALENCE STANDARDS SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Article; Book Chapter ID HIGHLY VARIABLE DRUGS; DOSAGE ADJUSTMENT; PRODUCTS C1 [Jiang, Wenlei; Yu, Lawrence X.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Jiang, WL (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Wenlei.Jiang@fda.hhs.gov NR 35 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2210-7371 BN 978-1-4939-1252-0; 978-1-4939-1251-3 J9 AAPS ADV PHARM SCI PY 2014 BP 191 EP 216 DI 10.1007/978-1-4939-1252-0_8 D2 10.1007/978-1-4939-1252-0 PG 26 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BC1TO UT WOS:000350418100010 ER PT S AU Zou, P Yu, LX AF Zou, Peng Yu, Lawrence X. BE Yu, LX Li, BV TI Pharmacodynamic Endpoint Bioequivalence Studies SO FDA BIOEQUIVALENCE STANDARDS SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Article; Book Chapter ID DERMATOLOGICAL DRUG PRODUCTS; BIOAVAILABILITY; INFLAMMATION; FORMULATIONS; BUDESONIDE; ASTHMA; ASSAY C1 [Zou, Peng; Yu, Lawrence X.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Zou, P (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Peng.Zou@fda.hhs.gov NR 47 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2210-7371 BN 978-1-4939-1252-0; 978-1-4939-1251-3 J9 AAPS ADV PHARM SCI PY 2014 BP 217 EP 241 DI 10.1007/978-1-4939-1252-0_9 D2 10.1007/978-1-4939-1252-0 PG 25 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BC1TO UT WOS:000350418100011 ER PT S AU Peters, JR AF Peters, John R. BE Yu, LX Li, BV TI Clinical Endpoint Bioequivalence Study SO FDA BIOEQUIVALENCE STANDARDS SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Article; Book Chapter ID HEPATIC-ENCEPHALOPATHY; CARDIOVASCULAR-DISEASE; TRAVELERS DIARRHEA; MEDICAL-EDUCATION; DRUG DEVELOPMENT; FLEXNER REPORT; RIFAXIMIN; BIOMARKERS; QUANTIFICATION; DISCOVERY C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Peters, JR (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Johnr.Peters@fda.hhs.gov NR 38 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2210-7371 BN 978-1-4939-1252-0; 978-1-4939-1251-3 J9 AAPS ADV PHARM SCI PY 2014 BP 243 EP 274 DI 10.1007/978-1-4939-1252-0_10 D2 10.1007/978-1-4939-1252-0 PG 32 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BC1TO UT WOS:000350418100012 ER PT S AU Zheng, N Jiang, WL Lionberger, R Yu, LX AF Zheng, Nan Jiang, Wenlei Lionberger, Robert Yu, Lawrence X. BE Yu, LX Li, BV TI Bioequivalence for Liposomal Drug Products SO FDA BIOEQUIVALENCE STANDARDS SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Article; Book Chapter ID ACCELERATED BLOOD CLEARANCE; IN-VITRO; SOLID TUMORS; DOXORUBICIN FORMULATIONS; THERAPEUTIC ACTIVITY; REPEATED INJECTION; LIPOPHILIC DRUGS; DELIVERY SYSTEMS; SURFACE-CHARGE; AMPHOTERICIN-B C1 [Zheng, Nan; Jiang, Wenlei; Lionberger, Robert; Yu, Lawrence X.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Zheng, N (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM nan.zheng@fda.hhs.gov; wenlei.jiang@fda.hhs.gov; robert.lionberger@fda.hhs.gov; lawrence.yu@fda.hhs.gov NR 74 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2210-7371 BN 978-1-4939-1252-0; 978-1-4939-1251-3 J9 AAPS ADV PHARM SCI PY 2014 BP 275 EP 296 DI 10.1007/978-1-4939-1252-0_11 D2 10.1007/978-1-4939-1252-0 PG 22 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BC1TO UT WOS:000350418100013 ER PT S AU Jiang, XJ Yang, YS Stier, E AF Jiang, Xiaojian Yang, Yongsheng Stier, Ethan BE Yu, LX Li, BV TI Bioequivalence for Drug Products Acting Locally Within Gastrointestinal Tract SO FDA BIOEQUIVALENCE STANDARDS SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Article; Book Chapter ID CHRONIC-RENAL-FAILURE; TYPE-2 DIABETES-MELLITUS; BINDER LANTHANUM CARBONATE; CHRONIC KIDNEY-DISEASE; COLESEVELAM HYDROCHLORIDE; IN-VITRO; PHOSPHATE BINDER; HEALTHY-VOLUNTEERS; ULCERATIVE-COLITIS; DOSAGE FORMS C1 [Jiang, Xiaojian; Yang, Yongsheng; Stier, Ethan] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Jiang, XJ (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Xiaojian.Jiang@fda.hhs.gov NR 109 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2210-7371 BN 978-1-4939-1252-0; 978-1-4939-1251-3 J9 AAPS ADV PHARM SCI PY 2014 BP 297 EP 334 DI 10.1007/978-1-4939-1252-0_12 D2 10.1007/978-1-4939-1252-0 PG 38 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BC1TO UT WOS:000350418100014 ER PT S AU Braddy, AC Conner, DP AF Braddy, April C. Conner, Dale P. BE Yu, LX Li, BV TI Bioequivalence for Topical Drug Products SO FDA BIOEQUIVALENCE STANDARDS SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Article; Book Chapter ID IN-VIVO; PERCUTANEOUS-ABSORPTION; HUMAN SKIN; DERMATOLOGICAL PRODUCTS; GENERIC DEVELOPMENT; DERMAL ABSORPTION; MICRODIALYSIS; DELIVERY; VITRO; BIOAVAILABILITY C1 [Braddy, April C.; Conner, Dale P.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Braddy, AC (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM April.Braddy@fda.hhs.gov NR 61 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2210-7371 BN 978-1-4939-1252-0; 978-1-4939-1251-3 J9 AAPS ADV PHARM SCI PY 2014 BP 335 EP 367 DI 10.1007/978-1-4939-1252-0_13 D2 10.1007/978-1-4939-1252-0 PG 33 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BC1TO UT WOS:000350418100015 ER PT S AU Saluja, B Li, BV Lee, SL AF Saluja, Bhawana Li, Bing V. Lee, Sau L. BE Yu, LX Li, BV TI Bioequivalence for Orally Inhaled and Nasal Drug Products SO FDA BIOEQUIVALENCE STANDARDS SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Article; Book Chapter ID METERED-DOSE INHALERS; ASTHMATIC-PATIENTS; DELIVERY-SYSTEMS; NITRIC-OXIDE; FORMULATION; PERFORMANCE; METHACHOLINE; SALMETEROL; DEPOSITION; HISTAMINE C1 [Saluja, Bhawana; Li, Bing V.; Lee, Sau L.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Lee, SL (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM sau.lee@fda.hhs.gov NR 44 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2210-7371 BN 978-1-4939-1252-0; 978-1-4939-1251-3 J9 AAPS ADV PHARM SCI PY 2014 BP 369 EP 394 DI 10.1007/978-1-4939-1252-0_14 D2 10.1007/978-1-4939-1252-0 PG 26 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BC1TO UT WOS:000350418100016 ER PT S AU Zhang, XY AF Zhang, Xinyuan BE Yu, LX Li, BV TI Bioequivalence: Modeling and Simulation SO FDA BIOEQUIVALENCE STANDARDS SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Article; Book Chapter ID ORAL-DRUG ABSORPTION; MONTE-CARLO SIMULATIONS; CONCENTRATION-TIME PROFILES; HIGHLY VARIABLE DRUGS; BIOPHARMACEUTICS CLASSIFICATION-SYSTEM; DETAILED PHYSIOLOGICAL MODEL; PARTICLE-SIZE DISTRIBUTION; IN-VITRO CORRELATION; SOLID DOSAGE FORMS; MIXING-TANK MODEL C1 US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Zhang, XY (reprint author), US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM Xinyuan.Zhang@fda.hhs.gov NR 112 TC 0 Z9 0 U1 6 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2210-7371 BN 978-1-4939-1252-0; 978-1-4939-1251-3 J9 AAPS ADV PHARM SCI PY 2014 BP 395 EP 417 DI 10.1007/978-1-4939-1252-0_15 D2 10.1007/978-1-4939-1252-0 PG 23 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BC1TO UT WOS:000350418100017 ER PT S AU Subramaniam, S AF Subramaniam, Sriram BE Yu, LX Li, BV TI Bioanalysis SO FDA BIOEQUIVALENCE STANDARDS SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Article; Book Chapter ID CHROMATOGRAPHY-MASS SPECTROMETRY; LIGAND-BINDING ASSAYS; LC-MS; LIQUID-CHROMATOGRAPHY; INCURRED SAMPLE; RECENT ISSUES; METHOD VALIDATION; HUMAN PLASMA; WHITE PAPER; REGULATED BIOANALYSIS C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Subramaniam, S (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Sriram.Subramaniam@fda.hhs.gov NR 58 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2210-7371 BN 978-1-4939-1252-0; 978-1-4939-1251-3 J9 AAPS ADV PHARM SCI PY 2014 BP 419 EP 458 DI 10.1007/978-1-4939-1252-0_16 D2 10.1007/978-1-4939-1252-0 PG 40 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BC1TO UT WOS:000350418100018 ER PT S AU Iacono, MI Neufeld, E Bonmassar, G Akinnagbe, E Jakab, A Cohen, E Kuster, N Kainz, W Angelone, LM AF Iacono, Maria I. Neufeld, Esra Bonmassar, Giorgio Akinnagbe, Esther Jakab, Andras Cohen, Ethan Kuster, Niels Kainz, Wolfgang Angelone, Leonardo M. GP IEEE TI A Computational Model for Bipolar Deep Brain Stimulation of the Subthalamic Nucleus SO 2014 36TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 36th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC) CY AUG 26-30, 2014 CL Chicago, IL SP IEEE Engn Medicine & Biol Soc AB Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown to reduce some of the symptoms of advanced, levodopa-responsive Parkinson's disease that are not adequately controlled with medication. However, the precise mechanism of the therapeutic action of DBS is still unclear. Stimulation-induced side effects are not uncommon and require electrical "dose" adjustments. Quantitative methods are needed to fully characterize the electric field in the deep brain region that surrounds the electrodes in order to help with adjustments and maximize the efficacy of the device. Herein we report a magnetic resonance imaging (MRI)-based head model proposed for analysis of fields generated by deep brain stimulation (DBS). The model was derived from multimodal image data at 0.5mm isotropic spatial resolution and distinguishes 142 anatomical structures, including the basal ganglia and 38 nuclei of the thalamus. Six bipolar electrode configurations (1-2, 1-3, 1-4, 2-3, 2-4, 3-4) were modeled in order to assess the effects of the inter-electrode distance of the electric field. Increasing the distance between the electrodes results in an attenuated stimulation, with up to 25% reduction in electric field amplitude delivered (2-3 vs. 1-4). The map of the deep brain structures provided a highly precise anatomical detail which is useful for the quantitative assessment of current spread around the electrode and a better evaluation of the stimulation setting for the treatment optimization. C1 [Iacono, Maria I.; Akinnagbe, Esther; Cohen, Ethan; Kainz, Wolfgang; Angelone, Leonardo M.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Div Phys, Silver Spring, MD 20993 USA. [Neufeld, Esra; Kuster, Niels] Fdn Res Informat Technol Soc IT IS, CH-8004 Zurich, Switzerland. [Jakab, Andras] Med Univ Vienna, Computat Image Anal & Radiol Lab, A-1090 Vienna, Austria. [Bonmassar, Giorgio] MGH, AA Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. RP Iacono, MI (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Div Phys, Silver Spring, MD 20993 USA. EM Maria.Iacono@fda.hhs.gov NR 17 TC 1 Z9 1 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-7929-0 J9 IEEE ENG MED BIO PY 2014 BP 6258 EP 6261 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044706063 ER PT J AU Kish-Doto, J Scales, M Eguino-Medina, P Fitzgerald, T Tzeng, JP McCormack, LA O'Donoghue, A Oguntimein, O West, SL AF Kish-Doto, Julia Scales, Monica Eguino-Medina, Paula Fitzgerald, Tania Tzeng, Janice P. McCormack, Lauren A. O'Donoghue, Amie Oguntimein, Oluwamurewa West, Suzanne L. TI Preferences for Patient Medication Information: What Do Patients Want? SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID RHEUMATIC CONDITIONS; UNITED-STATES; ORGANIZATIONAL SIGNALS; ARTHRITIS; RECALL; TEXT; PREVALENCE; WOMEN; MEN AB This study investigated respondent preferences on how best to display patient medication information (PMI) that accompanies prescription medications to promote comprehension and appropriate usage. The authors identified 30 individuals diagnosed with select immune disorders, 30 with other chronic diseases, and 30 from the general public and had them review one of two PMI handouts that varied by format, organization, and content. The authors explored preferences for the PMI handout using one-on-one interviews. The authors analyzed the qualitative data to identify relevant themes and patterns using NVivo9 qualitative software. The majority of respondents noted that the formats of the two PMI handouts were more informative than those they currently receive from the pharmacist, with a preference for the 2-column, segmented design. However, respondent PMI preferences varied by age, education, and health status. Patients need simpler and more concise drug information to make better decisions about their health. Current PMI handouts are dense and complex, which can be confusing and not reader friendly. To improve PMI understandability and usefulness, the U.S. Food and Drug Administration is working with stakeholders, consumer advocates, and academics. Findings from this study may help inform future development of more user-friendly PMI. C1 [Kish-Doto, Julia] RTI Int, Rockville, MD 20852 USA. [Scales, Monica; Fitzgerald, Tania; Tzeng, Janice P.; McCormack, Lauren A.; West, Suzanne L.] RTI Int, Res Triangle Pk, NC USA. [Eguino-Medina, Paula] RTI Int, Washington, DC USA. [O'Donoghue, Amie; Oguntimein, Oluwamurewa] US FDA, Silver Spring, MD USA. RP Kish-Doto, J (reprint author), RTI Int, 6110 Execut Blvd,Suite 902, Rockville, MD 20852 USA. EM jkdoto@rti.org NR 27 TC 3 Z9 3 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. PY 2014 VL 19 SU 2 SI SI BP 77 EP 88 DI 10.1080/10810730.2014.946114 PG 12 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA CE5OI UT WOS:000351884600010 PM 25315585 ER PT S AU Mattes, W Yang, X Orr, MS Richter, P Mendrick, DL AF Mattes, William Yang, Xi Orr, Michael S. Richter, Patricia Mendrick, Donna L. BE Makowski, GS TI Biomarkers of Tobacco Smoke Exposure SO ADVANCES IN CLINICAL CHEMISTRY, VOL 67 SE Advances in Clinical Chemistry LA English DT Review; Book Chapter ID SURROGATE END-POINTS; LUNG-CANCER RISK; OPERATING CHARACTERISTIC CURVE; GENE-ENVIRONMENT INTERACTION; TANDEM MASS-SPECTROMETRY; HUMAN SALIVARY DNA; CIGARETTE SMOKERS; DRUG DEVELOPMENT; BRONCHIAL EPITHELIUM; CARDIOVASCULAR-DISEASE AB Diseases and death caused by exposure to tobacco smoke have become the single most serious preventable public health concern. Thus, biomarkers that can monitor tobacco exposure and health effects can play a critical role in tobacco product regulation and public health policy. Biomarkers of exposure to tobacco toxicants are well established and have been used in population studies to establish public policy regarding exposure to second-hand smoke, an example being the nicotine metabolite cotinine, which can be measured in urine. Biomarkers of biological response to tobacco smoking range from those indicative of inflammation to mRNA and microRNA patterns related to tobacco use and/or disease state. Biomarkers identifying individuals with an increased risk for a pathological response to tobacco have also been described. The challenge for any novel technology or biomarker is its translation to clinical and/or regulatory application, a process that requires first technical validation of the assay and then careful consideration of the context the biomarker assay may be used in the regulatory setting. Nonetheless, the current efforts to investigate new biomarker of tobacco smoke exposure promise to offer powerful new tools in addressing the health hazards of tobacco product use. This review will examine such biomarkers, albeit with a focus on those related to cigarette smoking. C1 [Mattes, William; Yang, Xi; Mendrick, Donna L.] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Off Sci, Ctr Tobacco Prod, Rockville, MD 20857 USA. RP Mattes, W (reprint author), US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM william.mattes@fda.hhs.gov NR 207 TC 6 Z9 6 U1 2 U2 15 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2423 BN 978-0-12-802267-2 J9 ADV CLIN CHEM JI Advan. Clin. Chem. PY 2014 VL 67 BP 1 EP 45 DI 10.1016/bs.acc.2014.09.001 PG 45 WC Medical Laboratory Technology SC Medical Laboratory Technology GA BC1AD UT WOS:000349890400002 PM 25735858 ER PT S AU Brorson, K Kendrick, B AF Brorson, Kurt Kendrick, Brent BE Schiel, JE Davis, DL Borisov, OV TI Perspectives on Well-Characterized Biological Proteins SO STATE-OF-THE-ART AND EMERGING TECHNOLOGIES FOR THERAPEUTIC MONOCLONAL ANTIBODY CHARACTERIZATION, VOL 1 - MONOCLONAL ANTIBODY THERAPEUTICS: STRUCTURE, FUNCTION, AND REGULATORY SPACE SE ACS Symposium Series LA English DT Article; Book Chapter ID MONOCLONAL-ANTIBODIES; LYSINE; HEAVY; ACID AB The public expects medicines, including biopharmaceuticals, to be pure, of high quality, and consistent between doses. A critical component of achieving this goal is establishment and control of the critical quality attributes (CQAs) of both the bulk protein drug substance and the final unit dosage form that is administered to the patient. A well-characterized biological protein is one where there is confidence that all features important for product safety and potency have been identified. In this chapter, an industry and a regulatory authority representative discuss perspectives on achieving the shared goal of making high-quality biopharmaceuticals available to the public. C1 [Brorson, Kurt] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. [Kendrick, Brent] Amgen Inc, Longmont, CO 80503 USA. RP Brorson, K (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. EM kurt.brorson@fda.hhs.gov NR 23 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-3026-2 J9 ACS SYM SER JI ACS Symp. Ser. PY 2014 VL 1176 BP 99 EP 116 D2 10.1021/bk-2014-1176 PG 18 WC Biochemistry & Molecular Biology; Immunology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Immunology; Pharmacology & Pharmacy GA BC0ZH UT WOS:000349873500005 ER PT S AU Freedberg, DI Selenko, P AF Freedberg, Daron I. Selenko, Philipp BE Dill, KA TI Live Cell NMR SO ANNUAL REVIEW OF BIOPHYSICS, VOL 43 SE Annual Review of Biophysics LA English DT Review; Book Chapter DE in-cell NMR; on-cell NMR; in-cell EPR; macromolecular crowding; excluded volume; soft interactions ID SOLID-STATE NMR; DYNAMIC NUCLEAR-POLARIZATION; XENOPUS-LAEVIS OOCYTES; ANGLE-SPINNING NMR; MAGNETIC-RESONANCE-SPECTROSCOPY; PROTEIN-PROTEIN INTERACTIONS; LIVING MAMMALIAN-CELLS; IN-CELL; ESCHERICHIA-COLI; F-19 NMR AB Ever since scientists realized that cells are the basic building blocks of all life, they have been developing tools to look inside them to reveal the architectures and mechanisms that define their biological functions. Whereas "looking into cells" is typically said in reference to optical microscopy, high-resolution in-cell and on-cell nuclear magnetic resonance (NMR) spectroscopy is a powerful method that offers exciting new possibilities for structural and functional studies in and on live cells. In contrast to conventional imaging techniques, in-and on-cell NMR methods do not provide spatial information on cellular biomolecules. Instead, they enable atomic-resolution insights into the native cell states of proteins, nucleic acids, glycans, and lipids. Here we review recent advances and developments in both fields and discuss emerging concepts that have been delineated with these methods. C1 [Freedberg, Daron I.] USDA, Lab Bacterial Polysaccharides, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Selenko, Philipp] Leibniz Inst Mol Pharmacol FMP Berlin, Dept NMR Supported Struct Biol, In Cell NMR Lab, D-13125 Berlin, Germany. RP Freedberg, DI (reprint author), USDA, Lab Bacterial Polysaccharides, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM daron.freedberg@fda.hhs.gov; selenko@fmp-berlin.de NR 109 TC 28 Z9 28 U1 17 U2 80 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1936-122X BN 978-0-8243-1843-7 J9 ANNU REV BIOPHYS JI Annu. Rev. Biophys. PY 2014 VL 43 BP 171 EP 192 DI 10.1146/annurev-biophys-051013-023136 PG 22 WC Biophysics SC Biophysics GA BB9LG UT WOS:000348434000008 PM 24895852 ER PT S AU Finley, JW Finley, JW Ellwood, K Hoadley, J AF Finley, John Weldon Finley, John Wescott Ellwood, Kathleen Hoadley, James BE Cousins, RJ TI Launching a New Food Product or Dietary Supplement in the United States: Industrial, Regulatory, and Nutritional Considerations SO ANNUAL REVIEW OF NUTRITION, VOL 34 SE Annual Review of Nutrition LA English DT Review; Book Chapter DE nutrition; food science; Food and Drug Administration; label claims; food product development; regulations ID PERCENT POLYMERIC COLOR; MONOMERIC ANTHOCYANINS; ANTIOXIDANT CAPACITY; CANCER PREVENTION; HEALTH-BENEFITS; BITTER TASTE; AMINO-ACIDS; SELENIUM; CRANBERRIES; CRITERIA AB Launching a new food/dietary supplement into the US market can be a confusing process to those unfamiliar with the food industry. Industry capability and product specifications are initial determinants of whether a candidate product can be manufactured in a reproducible manner and whether pilot production can be brought up to the market scale. Regulatory issues determine how a product can be produced and marketed; the primary federal institutions involved in regulations are the US Department of Agriculture, the Food and Drug Administration, and the Federal Trade Commission. A primary distinction is made between food and drugs, and no product may enter the food market if it is in part or whole a drug. Product safety is a major concern, and myriad regulations govern the determination of safety. Newfoods/dietary supplements are often marketed by health claims or structure/function claims, and there are specific regulations pertaining to claims. Not understanding the regulatory issues involved in developing a new product or failing to comply with associated regulations can have legal and financial repercussions. C1 [Finley, John Weldon] ARS, USDA, Beltsville, MD 20705 USA. [Finley, John Wescott] Louisiana State Univ, Sch Nutr & Food Sci, Baton Rouge, LA 70803 USA. [Ellwood, Kathleen; Hoadley, James] US FDA, College Pk, MD 20740 USA. RP Finley, JW (reprint author), ARS, USDA, Beltsville, MD 20705 USA. EM john.finley@ars.usda.gov; jfinley@agcenter.lsu.edu; kellwood@csmd.edu; jhoadley@easconsultinggroup.com NR 92 TC 3 Z9 3 U1 1 U2 20 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0199-9885 BN 978-0-8243-2834-4 J9 ANNU REV NUTR JI Annu. Rev. Nutr. PY 2014 VL 34 BP 421 EP 447 DI 10.1146/annurev-nutr-071813-105817 PG 27 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BB9MA UT WOS:000348455800018 PM 24850389 ER PT J AU Dufield, D Neubert, H Garofolo, F Kirkovsky, L Stevenson, L Dumont, I Kaur, S Xu, KY Alley, SC Szapacs, M Arnold, M Bansal, S Haidar, S Welink, J Le Blaye, O Wakelin-Smith, J Whale, E Ishii-Watabe, A Bustard, M Katori, N Amaravadi, L Aubry, AF Beaver, C Bergeron, A Cai, XY Cojocaru, L DeSilva, B Duggan, J Fluhler, E Gorovits, B Gupta, S Hayes, R Ho, S Ingelse, B King, L Levesque, A Lowes, S Ma, M Musuku, A Myler, H Olah, T Patel, S Rose, M Schultz, G Smeraglia, J Swanson, S Torri, A Vazvaei, F Wilson, A Woolf, E Xue, L Yang, TY AF Dufield, Dawn Neubert, Hendrik Garofolo, Fabio Kirkovsky, Leo Stevenson, Lauren Dumont, Isabelle Kaur, Surinder Xu, Keyang Alley, Stephen C. Szapacs, Matthew Arnold, Mark Bansal, Surendra Haidar, Sam Welink, Jan Le Blaye, Olivier Wakelin-Smith, Jason Whale, Emma Ishii-Watabe, Akiko Bustard, Mark Katori, Noriko Amaravadi, Lakshmi Aubry, Anne-Francoise Beaver, Chris Bergeron, Annik Cai, Xiao-Yan Cojocaru, Laura DeSilva, Binodh Duggan, Jeff Fluhler, Eric Gorovits, Boris Gupta, Swati Hayes, Roger Ho, Stacy Ingelse, Benno King, Lindsay Levesque, Ann Lowes, Steve Ma, Mark Musuku, Adrien Myler, Heather Olah, Timothy Patel, Shefali Rose, Mark Schultz, Gary Smeraglia, John Swanson, Steven Torri, Albert Vazvaei, Faye Wilson, Amanda Woolf, Eric Xue, Li Yang, Tong-Yuan TI 2014 White Paper on recent issues in bioanalysis: a full immersion in bioanalysis (Part 2-hybrid LBA/LCMS, ELN & regulatory agencies' input) SO BIOANALYSIS LA English DT Article ID VALIDATION GROUP WORKSHOP; CALIBRATION AB The 2014 8th Workshop on Recent Issues in Bioanalysis (8th WRIB), a 5-day full immersion in the evolving field of bioanalysis, took place in Universal City, California, USA. Close to 500 professionals from pharmaceutical and biopharmaceutical companies, contract research organizations and regulatory agencies worldwide convened to share, review, discuss and agree on approaches to address current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS, LBA approaches and immunogenicity. From the prolific discussions held during the workshop, specific recommendations are presented in this 2014 White Paper. As with the previous years' editions, this paper acts as a practical tool to help the bioanalytical community continue advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2014 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 2) covers the recommendations for Hybrid LBA/LCMS, Electronic Laboratory Notebook and Regulatory Agencies' Input. Part 1 (Small molecules bioanalysis using LCMS) was published in the Bioanalysis issue 6(22) and Part 3 (Large molecules bioanalysis using LBA and Immunogenicity) will be published in the Bioanalysis issue 6(24). C1 [Dufield, Dawn; Neubert, Hendrik; Gorovits, Boris; Xue, Li] Pfizer, Andover, MA USA. [Garofolo, Fabio; Dumont, Isabelle; Bergeron, Annik] Algorithme Pharma Inc, Montreal, PQ H7V 4B3, Canada. [Kirkovsky, Leo] Pfizer, San Diego, CA USA. [Stevenson, Lauren; Amaravadi, Lakshmi] Biogen Idec Inc, Cambridge, MA USA. [Kaur, Surinder; Xu, Keyang] Genentech Inc, San Francisco, CA 94080 USA. [Alley, Stephen C.] Seattle Genet Inc, Bothell, WA USA. [Szapacs, Matthew] GlaxoSmithKline, King Of Prussia, PA USA. [Alley, Stephen C.; Arnold, Mark; Aubry, Anne-Francoise; DeSilva, Binodh; Myler, Heather; Olah, Timothy] Bristol Myers Squibb Co, Princeton, NJ USA. [Bansal, Surendra; Vazvaei, Faye] Roche Innovat Ctr, New York, NY USA. [Haidar, Sam] US FDA, Silver Spring, MD USA. [Welink, Jan] Dutch MEB, Utrecht, Netherlands. [Le Blaye, Olivier] France ANSM, St Denis, France. [Wakelin-Smith, Jason; Whale, Emma] UK MHRA, London, England. [Ishii-Watabe, Akiko; Katori, Noriko] Japan MHLW NIHS, Tokyo, Japan. [Bustard, Mark] Hlth Canada, Ottawa, ON K1A 0L2, Canada. [Beaver, Chris] InVentiv Hlth Clin, Montreal, PQ, Canada. [Cai, Xiao-Yan] Merck, Kenilworth, NJ USA. [Cojocaru, Laura] Tandem Labs, West Trenton, NJ USA. [Duggan, Jeff] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. [Fluhler, Eric] Pfizer, Pearl River, NY USA. [Gupta, Swati] Allergan Pharmaceut Inc, Irvine, CA USA. [Hayes, Roger] MPI Res, Mattawan, MI USA. [Ho, Stacy] Sanofi, Waltham, MA USA. [Ingelse, Benno] Merck, Oss, Netherlands. [King, Lindsay] Pfizer, Groton, CT USA. [Levesque, Ann] InVentiv Hlth Clin, Quebec City, PQ, Canada. [Lowes, Steve; Schultz, Gary] Quintiles, Ithaca, NY USA. [Ma, Mark; Rose, Mark; Swanson, Steven] Amgen Inc, Thousand Oaks, CA 91320 USA. [Musuku, Adrien] Pharmascience, Montreal, PQ, Canada. [Patel, Shefali; Yang, Tong-Yuan] Janssen Res & Dev, Spring House, PA USA. [Smeraglia, John] UCB Pharma, Braine Lalleud, Belgium. [Torri, Albert] Regeneron Pharmaceut, Tarrytown, NY USA. [Wilson, Amanda] AstraZeneca, Macclesfield, Cheshire, England. [Woolf, Eric] Merck Res Labs, West Point, PA USA. RP Garofolo, F (reprint author), Algorithme Pharma Inc, 575 Armand Frappier Blvd, Montreal, PQ H7V 4B3, Canada. EM fgarofolo@algopharm.com NR 12 TC 14 Z9 14 U1 1 U2 4 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 EI 1757-6199 J9 BIOANALYSIS JI Bioanalysis PY 2014 VL 6 IS 23 SI SI BP 3237 EP 3249 DI 10.4155/bio.14.279 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA CA8QP UT WOS:000349186300017 PM 25529890 ER PT J AU Subramaniam, S Stier, E Davit, BM AF Subramaniam, Sriram Stier, Ethan Davit, Barbara M. TI Incurred sample reanalysis in bioequivalence studies for abbreviated new drug applications SO BIOANALYSIS LA English DT Article DE abbreviated new drug applications; bioanalysis; bioequivalence studies; incurred sample reanalysis ID RECENT ISSUES; WHITE PAPER; HPLC-MS/MS; BIOANALYSIS; VALIDATION C1 [Subramaniam, Sriram; Stier, Ethan] US FDA, Div Bioequivalence 2, Off Gener Drugs, Silver Spring, MD 20993 USA. [Davit, Barbara M.] Merck Sharp & Dohme Corp, Whitehouse Stn, NJ USA. [Davit, Barbara M.] US FDA, Silver Spring, MD 20993 USA. RP Subramaniam, S (reprint author), US FDA, Div Bioequivalence 2, Off Gener Drugs, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM sriram.subramaniam@fda.hhs.gov NR 14 TC 0 Z9 0 U1 1 U2 2 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 EI 1757-6199 J9 BIOANALYSIS JI Bioanalysis PY 2014 VL 6 IS 24 BP 3349 EP 3354 DI 10.4155/bio.14.232 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA CA8QW UT WOS:000349187000009 PM 25534791 ER PT J AU Stevenson, L Amaravadi, L Myler, H Salazar-Fontana, L Gorovits, B Kirshner, S Xue, L Garofolo, F Alley, SC Thway, T Joyce, A Bansal, S Beaver, C Bergeron, A Cai, XY Cojocaru, L DeSilva, B Dumont, I Fluhler, E Fraser, S Gouty, D Gupta, S Haidar, S Hayes, R Ingelse, B Ishii-Watabe, A Kaur, S King, L Laterza, O Leung, S Levesque, A Ma, M Petit-Frere, C Pillutla, R Rose, M Schultz, G Smeraglia, J Swanson, S Torri, A Vazvaei, F Wakelin-Smith, J Wilson, A Woolf, E Yang, TY AF Stevenson, Lauren Amaravadi, Lakshmi Myler, Heather Salazar-Fontana, Laura Gorovits, Boris Kirshner, Susan Xue, Li Garofolo, Fabio Alley, Stephen C. Thway, Theingi Joyce, Alison Bansal, Surendra Beaver, Chris Bergeron, Annik Cai, Xiao-Yan Cojocaru, Laura DeSilva, Binodh Dumont, Isabelle Fluhler, Eric Fraser, Stephanie Gouty, Dominique Gupta, Swati Haidar, Sam Hayes, Roger Ingelse, Benno Ishii-Watabe, Akiko Kaur, Surinder King, Lindsay Laterza, Omar Leung, Sheldon Levesque, Ann Ma, Mark Petit-Frere, Corinne Pillutla, Renuka Rose, Mark Schultz, Gary Smeraglia, John Swanson, Steven Torri, Albert Vazvaei, Faye Wakelin-Smith, Jason Wilson, Amanda Woolf, Eric Yang, Tong-Yuan TI 2014 White Paper on recent issues in bioanalysis: a full immersion in bioanalysis (Part 3-LBA and immunogenicity) SO BIOANALYSIS LA English DT Article ID VALIDATION GROUP WORKSHOP; POLYETHYLENE-GLYCOL; REGULATED BIOANALYSIS; GLOBAL HARMONIZATION; REFRACTORY GOUT; ANTIBODY; RECOMMENDATIONS; IMPACT; PEG; BIOTHERAPEUTICS AB The 2014 8th Workshop on Recent Issues in Bioanalysis (8thWRIB), a 5-day full immersion in the evolving field of bioanalysis, took place in Universal City, California, USA. Close to 500 professionals from pharmaceutical and biopharmaceutical companies, contract research organizations and regulatory agencies worldwide convened to share, review, discuss and agree on approaches to address current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS, LBA approaches and immunogenicity. From the prolific discussions held during the workshop, specific recommendations are presented in this 2014 White Paper. As with the previous years' editions, this paper acts as a practical tool to help the bioanalytical community continue advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2014 edition of this comprehensive White Paper has been divided into three partsfor editorial reasons. This publication (Part 3) covers the recommendations for Large molecules bioanalysis using LBA and Immunogenicity. Part 1 (Small molecules bioanalysis using LCMS) and Part 2 (Hybrid LBA/LCMS, Electronic Laboratory Notebook and Regulatory Agencies' Input) were published in the Bioanalysis issues 6(22) and 6(23), respectively. C1 [Stevenson, Lauren; Amaravadi, Lakshmi] Biogen Idec Inc, Cambridge, MA USA. [Myler, Heather; DeSilva, Binodh; Pillutla, Renuka] Bristol Myers Squibb Co, Princeton, NJ USA. [Salazar-Fontana, Laura; Kirshner, Susan; Haidar, Sam] US FDA, Silver Spring, MD USA. [Gorovits, Boris; Xue, Li; Joyce, Alison; Leung, Sheldon] Pfizer, Andover, MA USA. [Garofolo, Fabio; Bergeron, Annik; Dumont, Isabelle] Algorithme Pharma Inc, Montreal, PQ H7V 4B3, Canada. [Alley, Stephen C.] Seattle Genet Inc, Bothell, WA USA. [Thway, Theingi; Ma, Mark; Rose, Mark; Swanson, Steven] Amgen Inc, Thousand Oaks, CA 91320 USA. [Bansal, Surendra; Vazvaei, Faye] Roche Innovat Ctr, New York, NY USA. [Beaver, Chris] InVentiv Hlth Clin, Montreal, PQ, Canada. [Cai, Xiao-Yan] Merck, Kenilworth, NJ USA. [Cojocaru, Laura] Tandem Labs, West Trenton, NJ USA. [Fluhler, Eric] Pfizer, Pearl River, NY USA. [Fraser, Stephanie; King, Lindsay] Pfizer, Groton, CT USA. [Gouty, Dominique] Intertek, San Diego, CA USA. [Gupta, Swati] Allergan Pharmaceut Inc, Irvine, CA USA. [Hayes, Roger] MPI Res, Mattawan, MI USA. [Ingelse, Benno] Merck, Oss, Netherlands. [Ishii-Watabe, Akiko] Japan MHLW NIHS, Tokyo, Japan. [Kaur, Surinder] Genentech Inc, San Francisco, CA 94080 USA. [Laterza, Omar] Merck, Whitehouse Stn, NJ USA. [Levesque, Ann] InVentiv Hlth Clin, Quebec City, PQ, Canada. [Petit-Frere, Corinne] Roche Innovat Ctr, Basel, Switzerland. [Schultz, Gary] Quintiles, Ithaca, NY USA. [Smeraglia, John] UCB Pharma, Braine Lalleud, Belgium. [Torri, Albert] Regeneron Pharmaceut, Tarrytown, NY USA. [Wakelin-Smith, Jason] UK MHRA, London, England. [Wilson, Amanda] AstraZeneca, Macclesfield, Cheshire, England. [Woolf, Eric] Merck Res Labs, West Point, PA USA. [Yang, Tong-Yuan] Janssen Res & Dev, Spring House, PA USA. RP Garofolo, F (reprint author), Algorithme Pharma Inc, 575 Armand Frappier Blvd, Montreal, PQ H7V 4B3, Canada. EM fgarofolo@algopharm.com FU US FDA; Europe EMA; Health Canada; France ANSM; The Netherlands MEB; Austria AGES; Germany BfArM; Japan MHWL; UK MHRA FX The authors would like to acknowledge the US FDA, Europe EMA, Health Canada, France ANSM, The Netherlands MEB, Austria AGES, Germany BfArM, Japan MHWL and UK MHRA for supporting this workshop. L Stevenson (Biogen Idec), L Amaravadi (Biogen Idec), H Myler (Bristol-Myers Squibb), D Dufield (Pfizer), L Salazar-Fontana (FDA), H Neubert (Pfizer), L Kirkovsky (Pfizer), F Garofolo (Algorithme Pharma), I Dumont (Algorithme Pharma), B Gorovits (Pfizer), E Fluhler (Pfizer), R Hayes (MPI Research), K Xu (Genentech), M Arnold (Bristol-Myers Squibb), S Bansal (Roche), T Verhaeghe (Janssen), A Bergeron (Algorithme Pharma), O Laterza (Merck), SC Alley (Seattle Genetics), M Szapacs (GlaxoSmithKline), A Wilson (AstraZeneca), S Kaur (Genentech) and A Joyce (Pfizer), for their major contribution in this White Paper. E Fluhler (Pfizer), O Le Blaye (France ANSM), D Dufield (Pfizer), L Amaravadi (Biogen Idec), L Stevenson (Biogen Idec) and F Garofolo (Algorithme Pharma) for chairing the workshop. E Fluhler (Pfizer), D Dufield (Pfizer), L Amaravadi (Biogen Idec) and L Stevenson (Biogen Idec) for chairing the White Paper discussions. All the workshop attendees and members of the bioanalytical community who have sent comments and suggestions to complete this White Paper. W Garofolo, L Lu, X Wang, E Petrova, M Losauro and B Felcyn for the logistic assistance of the event. Future Science Group as a trusted partner. NR 31 TC 10 Z9 10 U1 0 U2 0 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 EI 1757-6199 J9 BIOANALYSIS JI Bioanalysis PY 2014 VL 6 IS 24 BP 3355 EP 3368 DI 10.4155/bio.14.283 PG 14 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA CA8QW UT WOS:000349187000010 PM 25534792 ER PT J AU Dorr, H Lamkowski, A Graessle, DH Bennett, A Shapiro, A Farese, AM Garofalo, M MacVittie, TJ Meineke, V AF Doerr, Harald Lamkowski, Andreas Graessle, Dieter H. Bennett, Alexander Shapiro, Alla Farese, Ann M. Garofalo, Michael MacVittie, Thomas J. Meineke, Viktor TI LINKING THE HUMAN RESPONSE TO UNPLANNED RADIATION AND TREATMENT TO THE NONHUMAN PRIMATE RESPONSE TO CONTROLLED RADIATION AND TREATMENT SO HEALTH PHYSICS LA English DT Article DE blood; gastrointestinal tract; health effects; radiation effects ID MANAGEMENT; MODEL AB A key difficulty in developing countermeasures against radiation-induced health impairments is the clear lack of controlled clinical studies, due to the relatively low number of radiation victims worldwide. Instead, established and accepted animal models, as well as the recommendations of national and international expert panels and committees, are the main sources of information. Therefore, the development of countermeasures requires comparison of data from many sources and accumulation of information consistent with the U.S. Food and Drug Administration's "Animal Rule.'' A new approach is the comparative analysis of human data from the SEARCH (System for Evaluation and Archiving of Radiation Accidents based on Case Histories) database and data from nonhuman primate (NHP) animal model studies. The SEARCH database contains 824 clinical cases from 81 radiation accidents in 19 countries. This exceptional collection of clinical data from accidentally radiation-exposed persons is analyzed regarding clinical signs and symptoms of radiation-induced health impairments. To analyze the time course of radiation syndromes, clinical parameters common to the SEARCH and NHP databases have to be assigned into comparable categories of clinical severity for each species. The goal is to establish a method for comparison of human and NHP data, validate the NHP data as a surrogate for human efficacy/clinical studies, and open away for the extraction of diagnostic and treatment methods for humans after radiation exposure according to relevant regulations. C1 [Doerr, Harald; Lamkowski, Andreas; Graessle, Dieter H.; Meineke, Viktor] Univ Ulm, Bundeswehr Inst Radiobiol, D-80937 Munich, Germany. [Bennett, Alexander; Farese, Ann M.; Garofalo, Michael; MacVittie, Thomas J.] Univ Maryland, Sch Med, Dept Radiat Oncol, Baltimore, MD 21201 USA. [Shapiro, Alla] US FDA, Silver Spring, MD USA. RP Dorr, H (reprint author), Univ Ulm, Bundeswehr Inst Radiobiol, Neuherbergstr 11, D-80937 Munich, Germany. EM haralddoerr@bundeswehr.org FU National Institute of Allergy and Infectious Diseases (NIAID) [HHSN272201000046C] FX Contract Nr: HHSN272201000046C awarded to the University of Maryland, Baltimore (UMB) by National Institute of Allergy and Infectious Diseases (NIAID) for the project, "Radiation/Nuclear Medical Countermeasure Product Development Support Services." NR 7 TC 4 Z9 4 U1 0 U2 0 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 JAN PY 2014 VL 106 IS 1 BP 129 EP 134 DI 10.1097/HP.0b013e3182a12de0 PG 6 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 AZ9YW UT WOS:000348571700012 PM 24276556 ER PT J AU Lohne, JJ Agelarakis, AP AF Lohne, Jack J. Agelarakis, Anagnostis P. TI MULTIELEMENTAL ICP-MS ANALYSIS OF CLASSICAL PERIOD ARCHAEOLOGICAL CREMATED BONE AND SEDIMENT SAMPLES FROM DEMOSION SEMA POLYANDRIA OF SALAMINOS 35 SITE IN KERAMEIKOS, ATHENS, GREECE SO MEDITERRANEAN ARCHAEOLOGY & ARCHAEOMETRY LA English DT Article ID DIFFERENT HISTORICAL EPOCHS; HEAVY-METALS; ELEMENTAL ANALYSIS; TRACE-ELEMENTS; DIAGENESIS; JORDAN AB Cremated human bone fragments excavated at the monumental burial site at Salaminos 35 Street in Kerameikos of Athens, Greece, dated to the range of the 8th decade of the 5th century BC were the subject of anthropological study. A number of bone fragments included surface stains of various discolorations. The purpose of this interdisciplinary study combining a forensic anthropology-chemistry substrate was to determine which metal(s), if any, and under what circumstances may have caused the staining on the bone surfaces. To determine this, a Collision/Reaction Cell Inductively Coupled Plasma- Mass Spectrometry (CRC ICP-MS) method with microwave accelerated sample digestion was developed and validated for the quantification of metals in bone. The concentrations of Na, Mg, Al, K, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, As, Rb, Sr, Sn, Ba, Pb and U in the stained bone samples were compared to concentrations in unstained bone fragments and sediment samples from the same contextual archaeological association. The sample analyses and comparisons showed that 14 of the 15 stained bone samples analyzed contained significantly higher concentrations of various metals. Of the seven metals readily available during Classical antiquity (Au, Cu, Ag, Pb, Sri, Fe and Hg), four were detected at significantly high concentrations (Cu, Sn, Fe and Pb) in some samples, Ag was tested for but not detected in any sample while Au and Hg were not tested for. The metals that occurred most often at significantly high concentrations were Cu, Pb, Zn, As, Mg and Fe. C1 [Lohne, Jack J.] US FDA, ADRC, Lakewood, CO 80225 USA. [Agelarakis, Anagnostis P.] Adelphi Univ, Dept Anthropol, Garden City, NY 11530 USA. RP Agelarakis, AP (reprint author), Adelphi Univ, Dept Anthropol, Garden City, NY 11530 USA. EM agelarakis@adelphi.edu NR 38 TC 0 Z9 0 U1 2 U2 5 PU UNIV AGEAN, DEPT MEDITERRANEAN STUD PI RHODES PA 1 DEMOKRATIAS AV, RHODES, 85100, GREECE SN 1108-9628 J9 MEDITERR ARCHAEOL AR JI Mediterr. Archaeol. Archaeom. PY 2014 VL 14 IS 2 BP 243 EP 257 PG 15 WC Archaeology SC Archaeology GA AZ5ML UT WOS:000348264900017 ER PT J AU Guha, S Hariharan, P Myers, MR AF Guha, Suvajyoti Hariharan, Prasanna Myers, Matthew R. TI Enhancement of ICRP's Lung Deposition Model for Pathogenic Bioaerosols SO AEROSOL SCIENCE AND TECHNOLOGY LA English DT Article ID DIFFERENTIAL MOBILITY ANALYSIS; PUBLIC-HEALTH MANAGEMENT; RESPIRATORY-TRACT; PARTICLE DEPOSITION; AEROSOL DEPOSITION; INHALATIONAL ANTHRAX; RELATIVE-HUMIDITY; BIOLOGICAL WEAPON; INFLUENZA-VIRUS; RISK-ASSESSMENT AB Terrorist attacks using pathogenic bioaerosols pose a significant public-health threat. Modeling the risk associated with such attacks is valuable from the standpoint of disaster preparedness. To attain greater flexibility in bioterrorism risk modeling, we have developed an open-source lung deposition code based on the International Committee for Radiological Protection (ICRP) Publication 66 (ICRP 1994). This article describes modifications to ICRP's lung deposition model to fit the bioaerosol context and discusses the impact of exposure from a few monodisperse pathogenic toxins such as botulinum toxin, influenza virus, and Bacillus anthracis to infants and adults. As most existing commercial lung deposition codes are not open-source, this code provides users a platform template that can be modified to meet their needs. C1 [Guha, Suvajyoti; Hariharan, Prasanna; Myers, Matthew R.] US FDA, Div Appl Mech, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Guha, S (reprint author), US FDA, Div Appl Mech, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,WO62,Room 2233, Silver Spring, MD 20993 USA. EM Suvajyoti.Guha@fda.hhs.gov FU Medical Countermeasures Initiative team [MCM2DXXXXX20511, MCM2JXXXXX270HT] FX The authors would like to thank the Medical Countermeasures Initiative team for funding this project (MCM2DXXXXX20511, MCM2JXXXXX270HT). NR 66 TC 4 Z9 4 U1 3 U2 16 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0278-6826 EI 1521-7388 J9 AEROSOL SCI TECH JI Aerosol Sci. Technol. PY 2014 VL 48 IS 12 BP 1226 EP 1235 DI 10.1080/02786826.2014.975334 PG 10 WC Engineering, Chemical; Engineering, Mechanical; Environmental Sciences; Meteorology & Atmospheric Sciences SC Engineering; Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences GA AW6OH UT WOS:000346388200005 ER PT J AU Fluhler, E Hayes, R Garofolo, F Dumont, I Le Blaye, O Arnold, M Bansal, S Verhaeghe, T Wilson, A Stevenson, L Myler, H Bauer, R Bergeron, A Bustard, M Cai, XY Carbone, M Cojocaru, L Desai-Krieger, D Duggan, J Haidar, S Ho, S Ingelse, B Katori, N Levesque, A Lowes, S Ma, M Mettke, K Michon, J Musuku, A Olah, T Patel, S Rose, M Schultz, G Smeraglia, J Spooner, N Stouffer, B Vazvaei, F Wakelin-Smith, J Wang, J Welink, J Whale, E Woolf, E Xue, L Yang, TY AF Fluhler, Eric Hayes, Roger Garofolo, Fabio Dumont, Isabelle Le Blaye, Olivier Arnold, Mark Bansal, Surendra Verhaeghe, Tom Wilson, Amanda Stevenson, Lauren Myler, Heather Bauer, Ronald Bergeron, Annik Bustard, Mark Cai, Xiao-Yan Carbone, Mary Cojocaru, Laura Desai-Krieger, Daksha Duggan, Jeff Haidar, Sam Ho, Stacy Ingelse, Benno Katori, Noriko Levesque, Ann Lowes, Steve Ma, Mark Mettke, Katalina Michon, Josee Musuku, Adrien Olah, Timothy Patel, Shefali Rose, Mark Schultz, Gary Smeraglia, John Spooner, Neil Stouffer, Bruce Vazvaei, Faye Wakelin-Smith, Jason Wang, Jian Welink, Jan Whale, Emma Woolf, Eric Xue, Li Yang, Tong-Yuan TI 2014 White Paper on recent issues in bioanalysis: a full immersion in bioanalysis (Part 1-small molecules by LCMS) SO BIOANALYSIS LA English DT Article ID VALIDATION GROUP WORKSHOP; GLOBAL CRO COUNCIL; REGULATED BIOANALYSIS; RECOMMENDATIONS; CALIBRATION; STABILITY AB The 2014 8th Workshop on Recent Issues in Bioanalysis (8th WRIB), a 5-day full immersion in the evolving field of bioanalysis, took place in Universal City, California, USA. Close to 500 professionals from pharmaceutical and biopharmaceutical companies, contract research organizations and regulatory agencies worldwide convened to share, review, discuss and agree on approaches to address current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS, LBA approaches and immunogenicity. From the prolific discussions held during the workshop, specific recommendations are presented in this 2014 White Paper. As with the previous years' editions, this paper acts as a practical tool to help the bioanalytical community continue advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2014 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 1) covers the recommendations for small molecule bioanalysis using LCMS. Part 2 (Hybrid LBA/LCMS, Electronic Laboratory Notebook and Regulatory Agencies' input) and Part 3 (Large molecules bioanalysis using LBA and Immunogenicity) will be published in the upcoming issues of Bioanalysis. C1 [Fluhler, Eric] Pfizer, Pearl River, NY USA. [Hayes, Roger] MPI Res, Mattawan, MI USA. [Garofolo, Fabio; Dumont, Isabelle; Bergeron, Annik; Carbone, Mary] Algorithme Pharma Inc, Laval, PQ H7V 4B3, Canada. [Le Blaye, Olivier] France ANSM, St Denis, France. [Arnold, Mark; Myler, Heather; Olah, Timothy; Stouffer, Bruce; Wang, Jian] Bristol Myers Squibb Co, Princeton, NJ USA. [Bansal, Surendra; Vazvaei, Faye] Roche Innovat Ctr, New York, NY USA. [Verhaeghe, Tom] Janssen Res Dev, Beerse, Belgium. [Wilson, Amanda] AstraZeneca, Macclesfield, Cheshire, England. [Stevenson, Lauren] Biogen Idec Inc, Cambridge, MA USA. [Bauer, Ronald] Austria AGES, Vienna, Austria. [Bustard, Mark] Hlth Canada, Ottawa, ON K1A 0L2, Canada. [Cai, Xiao-Yan] Merck, Kenilworth, NJ USA. [Cojocaru, Laura] Tandem Labs, West Trenton, NJ USA. [Desai-Krieger, Daksha] Forest Labs Inc, Farmingdale, NY USA. [Haidar, Sam] Boehringer Ingelheim GmbH & Co KG, Ridgefield, CT USA. US FDA, Silver Spring, MD USA. [Ho, Stacy] Sanofi, Waltham, MA USA. [Ingelse, Benno] Merck, Oss, Netherlands. [Katori, Noriko] Japan MHLW NIHS, Tokyo, Japan. [Levesque, Ann] InVent Hlth Clin, Quebec City, PQ, Canada. [Lowes, Steve; Schultz, Gary] Quintiles, Ithaca, NY USA. [Ma, Mark; Rose, Mark] Amgen Inc, Thousand Oaks, CA 91320 USA. [Mettke, Katalina] Germany BfArM, Bonn, Germany. [Michon, Josee] Pharmascience, Montreal, PQ, Canada. [Musuku, Adrien; Patel, Shefali; Yang, Tong-Yuan] Janssen Res & Dev, Spring House, PA USA. [Smeraglia, John] UCB Pharma, Braine Lalleud, Belgium. [Spooner, Neil] GlaxoSmithKline, Ware, Herts, England. [Wakelin-Smith, Jason; Whale, Emma] UK MHRA, London, England. [Welink, Jan] Dutch MEB, Utrecht, Netherlands. [Duggan, Jeff; Woolf, Eric] Merck Res Labs, West Point, PA USA. [Xue, Li] Pfizer, Andover, MA USA. RP Garofolo, F (reprint author), Algorithme Pharma Inc, 575 Armand Frappier Blvd, Laval, PQ H7V 4B3, Canada. EM fgarofolo@algopharm.com FU US FDA; Europe EMA; Health Canada; France ANSM; Netherlands MEB; Austria AGES; Germany BfArM; Japan MHWL; UK MHRA FX The authors would like to acknowledge the US FDA, Europe EMA, Health Canada, France ANSM, The Netherlands MEB, Austria AGES, Germany BfArM, Japan MHWL and UK MHRA for supporting this workshop. L Stevenson (Biogen Idec), L Amaravadi (Biogen Idec), H Myler (Bristol-Myers Squibb), D Dufield (Pfizer), L Salazar-Fontana (FDA), H Neubert (Pfizer), L Kirkovsky (Pfizer), F Garofolo (Algorithme Pharma), I Dumont (Algorithme Pharma), B Gorovits (Pfizer), E Fluhler (Pfizer), R Hayes (MPI Research), K Xu (Genentech), M Arnold (Bristol-Myers Squibb), S Bansal (Roche), T Verhaeghe (Janssen), A Bergeron (Algorithme Pharma), O Laterza (Merck), SC Alley (Seattle Genetics), M Szapacs (GlaxoSmithKline), A Wilson (AstraZeneca), S Kaur (Genentech) and A Joyce (Pfizer), for their major contribution in this White Paper. E Fluhler (Pfizer), O Le Blaye (France ANSM), D Dufield (Pfizer), L Amaravadi (Biogen Idec), L Stevenson (Biogen Idec) and F Garofolo (Algorithme Pharma) for chairing the workshop. E Fluhler (Pfizer), D Dufield (Pfizer), L Amaravadi (Biogen Idec) and L Stevenson (Biogen Idec) for chairing the White Paper discussions. All the workshop attendees and members of the bioanalytical community who have sent comments and suggestions to complete this White Paper. W Garofolo, L Lu, X Wang, E Petrova, M Losauro and B Felcyn for the logistic assistance of the event. Future Science Group as a trusted partner. NR 13 TC 7 Z9 7 U1 1 U2 4 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 EI 1757-6199 J9 BIOANALYSIS JI Bioanalysis PY 2014 VL 6 IS 22 BP 3039 EP 3049 DI 10.4155/bio.14.265 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA AW4HR UT WOS:000346242300009 PM 25496256 ER PT J AU Khorasani, AA Weaver, JL Salvador-Morales, C AF Khorasani, Ali A. Weaver, James L. Salvador-Morales, Carolina TI Closing the gap: accelerating the translational process in nanomedicine by proposing standardized characterization techniques SO INTERNATIONAL JOURNAL OF NANOMEDICINE LA English DT Review DE physicochemical characterization; poly(ethylene glycol); protein adsorption; regulatory issues ID PLASMA-PROTEIN ADSORPTION; ELECTRON-MICROSCOPY TOMOGRAPHY; PEG CHAIN-LENGTH; X-RAY-SCATTERING; DRUG-DELIVERY; RAMAN-SPECTROSCOPY; COMPLEMENT ACTIVATION; CARBON NANOTUBES; SURFACE FUNCTIONALIZATION; ENGINEERED NANOMATERIALS AB On the cusp of widespread permeation of nanomedicine, academia, industry, and government have invested substantial financial resources in developing new ways to better treat diseases. Materials have unique physical and chemical properties at the nanoscale compared with their bulk or small-molecule analogs. These unique properties have been greatly advantageous in providing innovative solutions for medical treatments at the bench level. However, nanomedicine research has not yet fully permeated the clinical setting because of several limitations. Among these limitations are the lack of universal standards for characterizing nanomaterials and the limited knowledge that we possess regarding the interactions between nanomaterials and biological entities such as proteins. In this review, we report on recent developments in the characterization of nanomaterials as well as the newest information about the interactions between nanomaterials and proteins in the human body. We propose a standard set of techniques for universal characterization of nanomaterials. We also address relevant regulatory issues involved in the translational process for the development of drug molecules and drug delivery systems. Adherence and refinement of a universal standard in nanomaterial characterization as well as the acquisition of a deeper understanding of nanomaterials and proteins will likely accelerate the use of nanomedicine in common practice to a great extent. C1 [Khorasani, Ali A.] George Mason Univ, Dept Chem & Biochem, Fairfax, VA 22030 USA. [Khorasani, Ali A.; Salvador-Morales, Carolina] George Mason Univ, Dept Bioengn, Fairfax, VA 22030 USA. [Khorasani, Ali A.; Salvador-Morales, Carolina] George Mason Univ, Krasnow Inst Adv Study, Fairfax, VA 22030 USA. [Weaver, James L.] Food & Drug Adm, Ctr Drug Evaluat & Res, Div Appl Regulatory Sci, Silver Spring, MD USA. RP Salvador-Morales, C (reprint author), George Mason Univ, Dept Bioengn, 4400 Univ Dr MS 1G5, Fairfax, VA 22030 USA. EM csalvado@gmu.edu FU CSM (Carolina Salvador-Morales) startup fund [162904]; George Mason University Graduate Research Assistantship from the CSM startup fund FX This work was supported by the CSM (Carolina Salvador-Morales) startup fund (162904). AAK is supported by a George Mason University Graduate Research Assistantship from the CSM startup fund. NR 127 TC 6 Z9 6 U1 1 U2 15 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2013 J9 INT J NANOMED JI Int. J. Nanomed. PY 2014 VL 9 BP 5729 EP 5751 DI 10.2147/IJN.S72479 PG 23 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA AU8CI UT WOS:000345823800001 PM 25525356 ER PT J AU Willett, C Rae, JC Goyak, KO Minsavage, G Westmoreland, C Andersen, M Avigan, M Duche, D Harris, G Hartung, T Jaeschke, H Kleensang, A Landesmann, B Martos, S Matevia, M Toole, C Rowan, A Schultz, T Seed, J Senior, J Shah, I Subramanian, K Vinken, M Watkins, P AF Willett, Catherine Rae, Jessica Caverly Goyak, Katy O. Minsavage, Gary Westmoreland, Carl Andersen, Melvin Avigan, Mark Duche, Daniel Harris, Georgina Hartung, Thomas Jaeschke, Hartmut Kleensang, Andre Landesmann, Brigitte Martos, Suzanne Matevia, Marilyn Toole, Colleen Rowan, Andrew Schultz, Terry Seed, Jennifer Senior, John Shah, Imran Subramanian, Kalyanasundaram Vinken, Mathieu Watkins, Paul TI Building Shared Experience to Advance Practical Application of Pathway-Based Toxicology: Liver Toxicity Mode-of-Action SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION LA English DT Article DE systems toxicology; pathways of toxicity; adverse outcome pathways; in vitro toxicology; liver toxicity ID PRIMARY HUMAN HEPATOCYTES; ADVERSE OUTCOME PATHWAY; ACETAMINOPHEN HEPATOTOXICITY; RISK-ASSESSMENT; IPCS FRAMEWORK; 21ST-CENTURY; VISION; INHIBITION; MECHANISMS; RELEVANCE AB A workshop sponsored by the Human Toxicology Project Consortium (HTPC), "Building Shared Experience to Advance Practical Application of Pathway-Based Toxicology: Liver Toxicity Mode-of-Action" brought together experts from a wide range of perspectives to inform the process of pathway development and to advance two prototype pathways initially developed by the European Commission Joint Research Center (JRC): liver-specific fibrosis and steatosis. The first half of the workshop focused on the theory and practice of pathway development; the second on liver disease and the two prototype pathways. Participants agreed pathway development is extremely useful for organizing information and found that focusing the theoretical discussion on a specific AOP is helpful. It is important to include several perspectives during pathway development, including information specialists, pathologists, human health and environmental risk assessors, and chemical and product manufacturers, to ensure the biology is well captured and end use is considered. C1 [Willett, Catherine; Matevia, Marilyn; Rowan, Andrew] Humane Soc United States, Washington, DC 20037 USA. [Rae, Jessica Caverly] DuPont Haskell Global Ctr Hlth & Environm Sci, Newark, DE USA. [Goyak, Katy O.; Minsavage, Gary] ExxonMobil Biomed Sci Inc, Annandale, NJ USA. [Westmoreland, Carl] Unilever Res Labs, Safety & Environm Assurance Ctr, Sharnbrook, Beds, England. [Andersen, Melvin] Hamner Inst Hlth Sci, Res Triangle Pk, NC USA. [Avigan, Mark; Senior, John] Ctr Drug Evaluat & Res Food & Drug Adm, Silver Spring, MD USA. [Duche, Daniel] LOreal Res & Innovat, Aulnay Sous Bois, France. [Harris, Georgina; Hartung, Thomas; Kleensang, Andre; Martos, Suzanne] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, CAAT, Baltimore, MD USA. [Harris, Georgina; Hartung, Thomas; Kleensang, Andre; Martos, Suzanne] Univ Konstanz, CAAT Europe, Constance, Germany. [Jaeschke, Hartmut] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Landesmann, Brigitte] European Commiss, Inst Hlth & Consumer Protect, Joint Res Ctr, Ispra, Italy. [Toole, Colleen] CeeTox Inc, Kalamazoo, MI USA. [Schultz, Terry] Univ Tennessee, Knoxville, TN USA. [Schultz, Terry] OECD Secretariat, Paris, France. [Seed, Jennifer] Environm Protect Agcy, Off Pollut Prevent & Tox, Risk Assessment Div, Washington, DC USA. [Shah, Imran] Environm Protect Agcy, Natl Ctr Computat Toxicol, Res Triangle Pk, NC USA. [Subramanian, Kalyanasundaram] Strand Life Sci, Bangalore, Karnataka, India. [Vinken, Mathieu] Vrije Univ Brussel, Brussels, Belgium. [Watkins, Paul] Hamner Inst Hlth Sci, Res Triangle Pk, NC USA. [Watkins, Paul] Univ N Carolina, Inst Drug Safety Sci, Chapel Hill, NC USA. RP Willett, C (reprint author), Humane Soc United States, 2100 L St NW, Washington, DC 20037 USA. EM kwillett@humanesociety.org RI Vinken, Mathieu/H-7513-2013; OI Vinken, Mathieu/0000-0001-5115-8893; Kleensang, Andre/0000-0002-4564-7399 FU NIEHS NIH HHS [T32 ES007141] NR 37 TC 8 Z9 8 U1 2 U2 6 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 2014 VL 31 IS 4 BP 500 EP 519 PG 20 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AU0JU UT WOS:000345310000011 PM 24535319 ER PT S AU Grosu, R Cherry, E Clarke, EM Cleaveland, R Dixit, S Fenton, FH Gao, SC Glimm, J Gray, RA Mangharam, R Ray, A Smolka, SA AF Grosu, Radu Cherry, Elizabeth Clarke, Edmund M. Cleaveland, Rance Dixit, Sanjay Fenton, Flavio H. Gao, Sicun Glimm, James Gray, Richard A. Mangharam, Rahul Ray, Arnab Smolka, Scott A. BE Margaria, T Steffen, B TI Compositional, Approximate, and Quantitative Reasoning for Medical Cyber-Physical Systems with Application to Patient-Specific Cardiac Dynamics and Devices SO LEVERAGING APPLICATIONS OF FORMAL METHODS, VERIFICATION AND VALIDATION: SPECIALIZED TECHNIQUES AND APPLICATIONS, PT II SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 6th International Symposium on Leveraging Applications of Formal Methods, Verification and Validation (ISoLA) CY OCT 08-11, 2014 CL Imperial, GREECE AB The design of bug-free and safe medical device software is challenging, especially in complex implantable devices that control and actuate organs who's response is not fully understood. Safety recalls of pacemakers and implantable cardioverter defibrillators between 1990 and 2000 affected over 600,000 devices. Of these, 200,000 or 41%, were due to firmware issues that continue to increase in frequency. According to the FDA, software failures resulted in 24% of all medical device recalls in 2011. There is currently no formal methodology or open experimental platform to test and verify the correct operation of medical-device software within the closed-loop context of the patient. The goal of this effort is to develop the foundations of modeling, synthesis and development of verified medical device software and systems from verified closed-loop models of the device and organ(s). Our research spans both implantable medical devices such as cardiac pacemakers and physiological control systems such as drug infusion pumps which have multiple networked medical systems. These devices are physically connected to the body and exert direct control over the physiology and safety of the patient. The focus of this effort is on (a) Extending current binary safety properties to quantitative verification; (b) Development of patient-specific models and therapies; (c) Multi-scale modeling of complex physiological phenomena and compositional reasoning across a range of model abstractions and refinements; and (d) Bridging the formal reasoning and automated generation of safe and effective software for future medical devices. C1 [Grosu, Radu; Glimm, James; Smolka, Scott A.] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Cherry, Elizabeth] Rochester Inst Technol, Rochester, NY USA. [Clarke, Edmund M.; Gao, Sicun] Carnegie Mellon Univ, Pittsburgh, PA USA. [Cleaveland, Rance] Univ Maryland, College Pk, MD USA. [Dixit, Sanjay; Mangharam, Rahul] Univ Pennsylvania, Philadelphia, PA USA. [Fenton, Flavio H.] Georgia Inst Technol, Atlanta, GA USA. [Gray, Richard A.] US FDA, Silver Spring, MD USA. [Ray, Arnab] Fraunhofer USA Ctr Expt Software Engn, E Lansing, MI USA. RP Grosu, R (reprint author), SUNY Stony Brook, Stony Brook, NY 11794 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-662-45231-8; 978-3-662-45230-1 J9 LECT NOTES COMPUT SC PY 2014 VL 8803 BP 356 EP 364 PG 9 WC Computer Science, Artificial Intelligence; Computer Science, Software Engineering; Computer Science, Theory & Methods SC Computer Science GA BB7GD UT WOS:000345509600026 ER PT J AU Gavrielides, MA Conway, C O'Flaherty, N Gallas, BD Hewitt, SM AF Gavrielides, Marios A. Conway, Catherine O'Flaherty, Neil Gallas, Brandon D. Hewitt, Stephen M. TI Observer Performance in the Use of Digital and Optical Microscopy for the Interpretation of Tissue-Based Biomarkers SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article ID CELLULAR IMAGING-SYSTEM; IN-SITU HYBRIDIZATION; BREAST-CANCER; VIRTUAL MICROSCOPY; SURGICAL PATHOLOGY; QUANTITATIVE IMMUNOHISTOCHEMISTRY; MULTISITE PERFORMANCE; HER2/NEU EXPRESSION; PROTEIN EXPRESSION; HER-2/NEU STATUS AB Background. We conducted a validation study of digital pathology for the quantitative assessment of tissue-based biomarkers with immunohistochemistry. Objective. To examine observer agreement as a function of viewing modality (digital versus optical microscopy), whole slide versus tissue microarray (TMA) review, biomarker type (HER2 incorporating membranous staining and Ki-67 with nuclear staining), and data type (continuous and categorical). Methods. Eight pathologists reviewed 50 breast cancer whole slides (25 stained with HER2 and 25 with Ki-67) and 2 TMAs (1 stained with HER2, 1 with Ki-67, each containing 97 cores), using digital and optical microscopy. Results. Results showed relatively high overall interobserver and intermodality agreement, with different patterns specific to biomarker type. For HER2, there was better interobserver agreement for optical compared to digital microscopy for whole slides as well as better interobserver and intermodality agreement for TMAs. For Ki-67, those patterns were not observed. Conclusions. The differences in agreement patterns when examining different biomarkers and different scoring methods and reviewing whole slides compared to TMA stress the need for validation studies focused on specific pathology tasks to eliminate sources of variability that might dilute findings. The statistical uncertainty observed in our analyses calls for adequate sampling for each individual task rather than pooling cases. C1 [Gavrielides, Marios A.; O'Flaherty, Neil; Gallas, Brandon D.] US FDA, Div Imaging Diagnost & Software Reliabil, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Conway, Catherine; Hewitt, Stephen M.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Conway, Catherine] Leica Biosyst, Vista, CA 92081 USA. RP Gavrielides, MA (reprint author), US FDA, Div Imaging Diagnost & Software Reliabil, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM marios.gavrielides@fda.hhs.gov OI Hewitt, Stephen/0000-0001-8283-1788 FU Food and Drug Administration's Office of Women's Health (OWH) FX The authors are grateful for the pathologists who participated in this study: Meghna Alimchandani, M. D., David Kleiner, M. D., Ph.D., Alina Nicolae, M. D., Tan Ngyuen, M. D., Stephen Hewitt M. D., Ph.D., Gregory Riedlinger, M. D., Ph.D., Jackie Wieneke, M. D., and Avi Rosenberg, M. D., Ph.D. The study would not be possible without their time and effort. The authors would also like to thank Wei-Chung Cheng, Ph.D., and Hugo Caseres for their assistance and expertise regarding monitor color calibration. This work was supported by the Food and Drug Administration's Office of Women's Health (OWH) through a research grant to Marios Gavrielides and Nicholas Petrick. 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 54 TC 0 Z9 0 U1 0 U2 2 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2210-7177 EI 2210-7185 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 2014 AR 157308 DI 10.1155/2014/157308 PG 10 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA AU1ZW UT WOS:000345416900001 ER PT S AU Hoinka, J Berezhnoy, A Sauna, ZE Gilboa, E Przytycka, TM AF Hoinka, Jan Berezhnoy, Alexey Sauna, Zuben E. Gilboa, Eli Przytycka, Teresa M. BE Sharan, R TI AptaCluster - A Method to Cluster HT-SELEX Aptamer Pools and Lessons from Its Application SO RESEARCH IN COMPUTATIONAL MOLECULAR BIOLOGY, RECOMB2014 SE Lecture Notes in Bioinformatics LA English DT Proceedings Paper CT 18th Annual International Conference on Research in Computational Molecular Biology (RECOMB) CY APR 02-05, 2014 CL Carnegie Mellon Univ, Pittsburgh, PA SP Univ Pittsburgh, Dept Computat & Syst Biol, Int Soc Computat Biol, US Natl Sci Fdn, Biomed Cent GigaScience, Carnegie Mellons Lane Ctr Computat Biol HO Carnegie Mellon Univ ID IL-10 AB Systematic Evolution of Ligands by EXponential Enrichment (SELEX) is a well established experimental procedure to identify aptamers - synthetic single-stranded (ribo) nucleic molecules that bind to a given molecular target. Recently, new sequencing technologies have revolutionized the SELEX protocol by allowing for deep sequencing of the selection pools after each cycle. The emergence of High Throughput SELEX (HT-SELEX) has opened the field to new computational opportunities and challenges that are yet to be addressed. To aid the analysis of the results of HT-SELEX and to advance the understanding of the selection process itself, we developed AptaCluster. This algorithm allows for an efficient clustering of whole HT-SELEX aptamer pools; a task that could not be accomplished with traditional clustering algorithms due to the enormous size of such datasets. We performed HT-SELEX with Interleukin 10 receptor alpha chain (IL-10RA) as the target molecule and used AptaCluster to analyze the resulting sequences. AptaCluster allowed for the first survey of the relationships between sequences in different selection rounds and revealed previously not appreciated properties of the SELEX protocol. As the first tool of this kind, AptaCluster enables novel ways to analyze and to optimize the HT-SELEX procedure. Our AptaCluster algorithm is available as a very fast multiprocessor implementation upon request. C1 [Hoinka, Jan; Przytycka, Teresa M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Berezhnoy, Alexey; Gilboa, Eli] Univ Miami, Sch Med, Dept Microbiol & Immunol, Miami, FL 33101 USA. [Sauna, Zuben E.] Food & Drug Adm, Ctr Biol Evaluat & Res, Lab Hemostasis, Div Hematol, Bethlehem, PA USA. RP Gilboa, E (reprint author), Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33101 USA. EM EGilboa@med.miami.edu; przytyck@ncbi.nlm.nih.gov FU Intramural Research Program of the NIH; National Library of Medicine (JH, TMP); Laboratory of Hemostasis and the Center for Biologics Evaluation and Research; Food and Drug Administration's Modernization of Science program (ZES); Dodson estate and the Sylvester Comprehensive Cancer Center, Medical School, University of Miami ( AB and EG) FX This work was supported in part by the Intramural Research Program of the NIH, National Library of Medicine (JH, TMP), in part funds from the Laboratory of Hemostasis and the Center for Biologics Evaluation and Research, Food and Drug Administration's Modernization of Science program (ZES), and in part by bequest from the Dodson estate and the Sylvester Comprehensive Cancer Center, Medical School, University of Miami ( AB and EG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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 19 TC 3 Z9 3 U1 1 U2 4 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0302-9743 BN 978-3-319-05269-4; 978-3-319-05268-7 J9 LECT N BIOINFORMAT JI Lect. Notes Bioinforma. PY 2014 VL 8394 BP 115 EP 128 PG 14 WC Biochemical Research Methods; Computer Science, Information Systems; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Mathematical & Computational Biology GA BB6XX UT WOS:000345119100009 ER PT S AU Vogt, WC Jia, CX Garra, BS Pfefer, TJ AF Vogt, William C. Jia, Congxian Garra, Brian S. Pfefer, T. Joshua BE Cullum, BM McLamore, ES TI Characterization of Tissue-Simulating Polymers for Photoacoustic Vascular Imaging SO SMART BIOMEDICAL AND PHYSIOLOGICAL SENSOR TECHNOLOGY XI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Smart Biomedical and Physiological Sensor Technology XI CY MAY 07-09, 2014 CL Baltimore, MD SP SPIE DE phantom; ultrasound; polyvinyl chloride; plastisol; optical properties; acoustic properties ID OPTICAL-PROPERTIES; MIMICKING PHANTOMS; HUMAN SKIN; TOMOGRAPHY; MAMMOGRAPHY; THICKNESS; INDEX; NM AB Photoacoustic tomography (PAT) is a maturing imaging technique which combines optical excitation and acoustic detection to enable deep tissue sensing for biomedical applications. Optical absorption provides biochemical specificity and high optical contrast while ultrasonic detection provides high spatial resolution and penetration depth. These characteristics make PAT highly suitable as an approach for vascular imaging. However, standard testing methods are needed in order to characterize and compare the performance of these systems. Tissue-mimicking phantoms are commonly used as standard test samples for imaging system development and evaluation due to their repeatable fabrication and tunable properties. The multi-domain mechanism behind PAT necessitates development of phantoms that accurately mimic both acoustic and optical properties of tissues. While a wide variety of materials have been used in the literature, from gelatin and agar hydrogels to silicone, published data indicates that poly(vinyl chloride) plastisol (PVCP) is a promising candidate material for simulating tissue optical and acoustic properties while also providing superior longevity and stability. Critical acoustic properties of PVCP phantoms, including sound velocity and attenuation, were measured using acoustic transmission measurements at multiple frequencies relevant to typical PAT systems. Optical absorption and scattering coefficients of PVCP gels with and without biologically relevant absorbers and scatterers were measured over wavelengths from 500 to 1100 nm. A custom PAT system was developed to assess image contrast in PVCP phantoms containing fluid channels filled with absorbing dye. PVCP demonstrates strong potential as the basis of high-fidelity polymer phantoms for developing and evaluating PAT systems for vascular imaging applications. C1 [Vogt, William C.; Jia, Congxian; Garra, Brian S.; Pfefer, T. Joshua] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Vogt, WC (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. NR 31 TC 1 Z9 1 U1 2 U2 9 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-044-0 J9 PROC SPIE PY 2014 VL 9107 AR 910719 DI 10.1117/12.2053583 PG 11 WC Engineering, Biomedical; Instruments & Instrumentation; Optics SC Engineering; Instruments & Instrumentation; Optics GA BB6WC UT WOS:000345067200028 ER PT S AU Woolsey, N Wang, HW Agrawal, A Wang, JT Liang, CP Chen, Y Pfefer, J AF Woolsey, Nicholas Wang, Hsing-Wen Agrawal, Anant Wang, Jianting Liang, Chia-Pin Chen, Yu Pfefer, Joshua BE Cullum, BM McLamore, ES TI Quantitative Analysis of Low Contrast Detectability in Optical Coherence Tomography SO SMART BIOMEDICAL AND PHYSIOLOGICAL SENSOR TECHNOLOGY XI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Smart Biomedical and Physiological Sensor Technology XI CY MAY 07-09, 2014 CL Baltimore, MD SP SPIE DE phantom; optical coherence tomography; contrast; detectability ID RESOLUTION; OCT; FEASIBILITY; ESOPHAGUS; PHANTOMS; CANCER; IMAGES AB Optical coherence tomography (OCT) is a high resolution imaging technology that is rapidly being adopted as the standard of care for medical applications such as ocular and intravascular imaging. However, clinical translation has been hampered by the lack of standardized test methods for performance evaluation as well as consensus standards analogous to those that have been developed for established medical imaging modalities (e. g., ultrasound). In this study, we address low contrast detectability, specifically, the ability of systems to differentiate between regions exhibiting small differences in scattering coefficient. Based on standard test methods for established medical imaging modalities, we have developed layered phantoms with well-characterized scattering properties in a biologically relevant range. The phantoms consisted of polydimethylsiloxane (PDMS) doped with varying concentrations of BaSO4 microparticles. Microfabrication processes were used to create layered and channel schemes. Two spectral domain OCT systems - a Fourier domain system at 855 nm and a swept-source device at 1310 nm - were then used to image the phantoms. The detectability of regions with different scattering levels was evaluated for each system by measuring pixel intensity differences. Confounding factors such as the inherent attenuation of the phantoms, signal intensity decay due to focusing and system roll-off were also encountered and addressed. Significant differences between systems were noted. The minimum differences in scattering coefficient that the Fourier domain and swept source systems could differentiate was 1.50 and 0.46 mm(-1) respectively. Overall, this approach to evaluating low contrast detectability represents a key step towards the development of standard test methods to facilitate clinical translation of novel OCT systems. C1 [Woolsey, Nicholas; Wang, Hsing-Wen; Wang, Jianting; Liang, Chia-Pin; Chen, Yu] Univ Maryland, Fischell Dept Engn, College Pk, MD 20742 USA. [Woolsey, Nicholas; Wang, Hsing-Wen; Agrawal, Anant; Wang, Jianting; Pfefer, Joshua] Food & Drug Adm, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Woolsey, N (reprint author), Univ Maryland, Fischell Dept Engn, College Pk, MD 20742 USA. FU NSF, CBET [1135514] FX The authors gratefully acknowledge support from the National Science Foundation's FDA Scholar-in-Residence program (NSF, CBET 1135514) for this project. 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 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 978-1-62841-044-0 J9 PROC SPIE PY 2014 VL 9107 AR UNSP 91070C DI 10.1117/12.2053721 PG 8 WC Engineering, Biomedical; Instruments & Instrumentation; Optics SC Engineering; Instruments & Instrumentation; Optics GA BB6WC UT WOS:000345067200006 ER PT S AU Mosley, SL AF Mosley, S. L. BE Komolprasert, V Turowski, P TI Framework for FDA's Review of Food Additives, Color Additives, GRAS Substances, and Food Contact Substances SO FOOD ADDITIVES AND PACKAGING SE ACS Symposium Series LA English DT Proceedings Paper CT Symposium on Food Additives and Packaging / 245th American-Chemical-Society National Meeting and Exposiiton CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc, Div Agr & Food Chem Inc AB The 1958 Food Additives Amendment to the Federal Food, Drug, and Cosmetic Act (FD&C Act) defined the term food additive and required producers to demonstrate to FDA the safety of a food additive under the intended conditions of use before it enters the market. In enacting this amendment, Congress recognized that many substances intentionally added to food would not require premarket approval to assure their safety because they were generally recognized as safe by experts qualified by scientific training and experience to evaluate their safety. Thus, the intended use of such substances was excluded from the definition of a food additive, and was termed generally recognized as safe (GRAS). Also, in 1960, Congress amended the FD&C Act again to establish premarket review for color additives. Lastly, in 1997, Congress amended the FD&C Act to establish a mandatory pre-market notification process for food contact substances, formerly known as indirect food additives. This chapter will discuss how the agency uses its authorities to ensure that substances and packaging materials in the food supply are safe. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, Div Biotechnol & GRAS Notice Review, College Pk, MD 20740 USA. RP Mosley, SL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, Div Biotechnol & GRAS Notice Review, 5100 Paint Branch Pkwy,HFS-255, College Pk, MD 20740 USA. EM Sylvester.Mosley@fda.hhs.gov NR 0 TC 0 Z9 0 U1 2 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-3024-8 J9 ACS SYM SER JI ACS Symp. Ser. PY 2014 VL 1162 BP 27 EP 34 PG 8 WC Chemistry, Multidisciplinary; Food Science & Technology SC Chemistry; Food Science & Technology GA BB6EC UT WOS:000344714000003 ER PT S AU Barrows, JN Lipman, AL Belai, N AF Barrows, Julie N. Lipman, Arthur L. Belai, Nebebech BE Komolprasert, V Turowski, P TI History of US Regulation of Color Additives and Colorants SO FOOD ADDITIVES AND PACKAGING SE ACS Symposium Series LA English DT Proceedings Paper CT Symposium on Food Additives and Packaging / 245th American-Chemical-Society National Meeting and Exposiiton CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc, Div Agr & Food Chem Inc ID FOOD; ANILINE; DYE AB Color additives are dyes, pigments, or other substances that impart color to foods, drugs, cosmetics, and certain medical devices. Colorants are similar substances that impart color to food contact materials such as packaging. The U.S. Food and Drug Administration has the responsibility for regulating color additives and colorants, and both have premarket approval requirements. Federal oversight began in the late 19th Century and continued with the 1906 Food and Drugs Act, 1938 Federal Food, Drug, and Cosmetic Act, and multiple amendments. This chapter combines the history of U.S. regulation of color additives and colorants. C1 [Barrows, Julie N.; Lipman, Arthur L.; Belai, Nebebech] US FDA, College Pk, MD 20740 USA. RP Barrows, JN (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM julie.barrows@fda.hhs.gov NR 39 TC 0 Z9 0 U1 3 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-3024-8 J9 ACS SYM SER JI ACS Symp. Ser. PY 2014 VL 1162 BP 57 EP 71 PG 15 WC Chemistry, Multidisciplinary; Food Science & Technology SC Chemistry; Food Science & Technology GA BB6EC UT WOS:000344714000006 ER PT S AU Thurmond, TS AF Thurmond, T. S. BE Komolprasert, V Turowski, P TI U. S. Food and Drug Administration's (FDA) Safety Assessment of Food Ingredients SO FOOD ADDITIVES AND PACKAGING SE ACS Symposium Series LA English DT Proceedings Paper CT Symposium on Food Additives and Packaging / 245th American-Chemical-Society National Meeting and Exposiiton CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc, Div Agr & Food Chem Inc AB The FDA's Center for Food Safety and Applied Nutrition (CFSAN) and Center for Veterinary Medicine have regulatory responsibility for approximately 80% of foods and food-related products consumed in the United States. The safety assessment of ingredients added directly to foods meant for human consumption is an important component of this responsibility. Before food ingredients such as certified colors, colors derived from natural sources, artificial sweeteners, leavening agents, etc., can be introduced into the food supply they require a safety decision that they present "... a reasonable certainty in the minds of competent scientists that the substance is not harmful under the intended conditions of use." This section will present a brief summary of the safety assessment process conducted for chemicals added to our food supply as food additives or color additives. It will also briefly discuss the current FDA draft regulatory guidance for the use of food-related products developed using nanotechnology, as well as some of the issues associated with toxicology testing of food ingredients developed using this technology. Lastly, it will discuss the potential for the incorporation of alternative in vitro and in vivo toxicity testing methods into the overall safety assessment paradigm. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, College Pk, MD 20740 USA. RP Thurmond, TS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, 5100 Paint Branch Pkwy,HFS-265, College Pk, MD 20740 USA. EM Scott.Thurmond@fda.hhs.gov NR 6 TC 1 Z9 1 U1 5 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-3024-8 J9 ACS SYM SER JI ACS Symp. Ser. PY 2014 VL 1162 BP 91 EP 95 PG 5 WC Chemistry, Multidisciplinary; Food Science & Technology SC Chemistry; Food Science & Technology GA BB6EC UT WOS:000344714000009 ER PT S AU Proffitt, LD AF Proffitt, Leah D. BE Komolprasert, V Turowski, P TI Environmental Review of Food Additive Submissions SO FOOD ADDITIVES AND PACKAGING SE ACS Symposium Series LA English DT Proceedings Paper CT Symposium on Food Additives and Packaging / 245th American-Chemical-Society National Meeting and Exposiiton CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc, Div Agr & Food Chem Inc AB Under the National Environmental Policy Act (NEPA) of 1969, federal agencies are required to consider environmental factors in their decision-making, and examine the environmental impacts of major, final actions. At FDA, these actions include but are not limited to petitions, (food- and color-additive, and citizen petitions), Threshold of Regulation (TOR) detemiinations, and allowing a Food Contact Notification (FCN) to become effective. Under FDA's NEPA implementing regulations, each of these submission types is required, to include an environmental component in the form of either a claim of categorical exclusion or an environmental assessment (EA). NEPA does not supplement or replace FDA's enabling statute, the Federal Food, Drug and Cosmetic Act (FFDCA). Categorical exclusions apply to actions that the agency has found do not individually or cumulatively affect the environment. Thus, categorical exclusions are very narrowly defined and precisely worded to fit very specific actions. EAs are required for any action for which there is no categorical exclusion, or where a categorical exclusion exists, but there are extraordinary circumstances that require further examination in an EA. The agency has developed guidance for what information to include in an EA to ensure that it provides the agency with sufficient information to determine whether an Environmental Impact Statement (EIS) or a Findings of No Significant Impact (FONSI) is appropriate. C1 US FDA, College Pk, MD 20740 USA. RP Proffitt, LD (reprint author), US FDA, 5100 Paint Branch Pkwy HFS-255, College Pk, MD 20740 USA. EM leah.proffitt@fda.hhs.gov NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-3024-8 J9 ACS SYM SER JI ACS Symp. Ser. PY 2014 VL 1162 BP 97 EP 103 PG 7 WC Chemistry, Multidisciplinary; Food Science & Technology SC Chemistry; Food Science & Technology GA BB6EC UT WOS:000344714000010 ER PT S AU Komolprasert, V AF Komolprasert, Vanee BE Komolprasert, V Turowski, P TI Evaluating Packaging Materials for Use during the Irradiation of Prepackaged Food SO FOOD ADDITIVES AND PACKAGING SE ACS Symposium Series LA English DT Proceedings Paper CT Symposium on Food Additives and Packaging / 245th American-Chemical-Society National Meeting and Exposiiton CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc, Div Agr & Food Chem Inc AB Irradiation is an effective means for controlling foodborne pathogens and has gained much interest from the food industry in the past two decades. Irradiation of prepackaged food is a reasonable and practical method to avoid the post-irradiation contamination of food, and additionally, the irradiated foods are ready for shipping to the market immediately after irradiation. Irradiation can induce chemical changes to the packaging materials resulting in the formation of breakdown products that may readily migrate into foods. Therefore, the packaging materials holding food being irradiated are required to undergo premarket authorization prior to use. This chapter addresses the interpretation of the food irradiation regulations, the effects of various types of radiation on food packaging materials, challenges for analyzing breakdown products, and some approaches for use in evaluating packaging materials for use during the irradiation of prepackaged food. C1 US FDA, Div Food Contact Notificat, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Komolprasert, V (reprint author), US FDA, Div Food Contact Notificat, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Vanee.Komolprasert@fda.hhs.gov NR 3 TC 1 Z9 1 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-3024-8 J9 ACS SYM SER JI ACS Symp. Ser. PY 2014 VL 1162 BP 119 EP 126 PG 8 WC Chemistry, Multidisciplinary; Food Science & Technology SC Chemistry; Food Science & Technology GA BB6EC UT WOS:000344714000012 ER PT S AU Song, YS AF Song, Yoon S. BE Komolprasert, V Turowski, P TI Effect of High Pressure Processing on Migration Characteristics in Polymer Films SO FOOD ADDITIVES AND PACKAGING SE ACS Symposium Series LA English DT Proceedings Paper CT Symposium on Food Additives and Packaging / 245th American-Chemical-Society National Meeting and Exposiiton CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc, Div Agr & Food Chem Inc ID HIGH HYDROSTATIC-PRESSURE; MASS-TRANSFER PROPERTIES; PACKAGING MATERIALS; GLASS-TRANSITION; ISOTACTIC POLYPROPYLENE; FOOD-PRODUCTS; COOLING RATE; CRYSTALLIZATION; STERILIZATION; BARRIER AB The use of polymer-based flexible packaging materials has allowed application of high pressure processing (HPP) to pre-packaged food products. Many of these materials have been shown to withstand different HPP conditions without significant loss of physical and mechanical properties. There are, however, still substantial gaps in scientific information surrounding the effect of pressure on food and packaging interactions. If HPP promotes migration of additives and other residual contaminants into foods in direct contact with the materials, it could possibly become a concern to public health. This chapter reviews the results of published research concerning (1) changes in morphological properties of the polymeric packaging materials under high pressure conditions and (2) HPP effects upon chemical migration from packaging materials and sorption of food constituents (flavor scalping) into packaging. C1 US FDA, Div Food Proc Sci & Technol HFS 450, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. RP Song, YS (reprint author), US FDA, Div Food Proc Sci & Technol HFS 450, Inst Food Safety & Hlth, 6502 South Archer Rd, Bedford Pk, IL 60501 USA. EM yoon.song@fda.hhs.gov NR 49 TC 0 Z9 0 U1 1 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-3024-8 J9 ACS SYM SER JI ACS Symp. Ser. PY 2014 VL 1162 BP 139 EP 154 PG 16 WC Chemistry, Multidisciplinary; Food Science & Technology SC Chemistry; Food Science & Technology GA BB6EC UT WOS:000344714000014 ER PT J AU Echevarria, D Gutfraind, A Boodram, B Major, ME Cotler, S Dahari, H AF Echevarria, Desarae Gutfraind, Alexander Boodram, Basmattee Major, Marian E. Cotler, Scott Dahari, Harel TI Modeling treatment scale up effect on hepatitis C prevalence among persons who inject drugs in metropolitan Chicago SO HEPATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-11, 2014 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Echevarria, Desarae; Gutfraind, Alexander; Cotler, Scott; Dahari, Harel] Loyola Univ, Med Ctr, Dept Med, Program Expt & Theoret Modeling,Div Hepatol, Maywood, IL 60153 USA. [Gutfraind, Alexander; Boodram, Basmattee] Univ Illinois, Sch Publ Hlth, Chicago, IL USA. [Major, Marian E.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Dahari, Harel] Los Alamos Natl Lab, Los Alamos, NM USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 974 BP 671A EP 672A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803023 ER PT S AU Lunn, G AF Lunn, George BE Town, WG Currano, JN TI Analytical Procedures and the Regulation of New Drug Development SO SCIENCE AND THE LAW: ANALYTICAL DATA IN SUPPORT OF REGULATION IN HEALTH, FOOD, AND THE ENVIRONMENT SE ACS Symposium Series LA English DT Proceedings Paper CT Symp on Science and the Law: Analytical Data in Support of Regulation in Health, Food, and the Environment / 244th Amer-Chem-Soc National Meeting and Exposition CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Chem Informat AB Within the United States Food and Drug Administration, the Center for Drug Evaluation and Research is responsible for the regulation of pharmaceuticals that are intended for marketing. In the broadest sense, the type of information that should be submitted to the Food and Drug Administration by the applicant is set by statute and the Code of Federal Regulations, along with various Guidance documents. The recommendations become more specific as we move from the statute to Guidance. The amount of information that should be supplied is determined by the stage of development. Generally, lesser amounts of information are supplied in the early stages and submissions become larger and more detailed as development proceeds. These principles are illustrated by the example of analytical procedures. C1 US FDA, Off New Drug Qual Assessment, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Lunn, G (reprint author), US FDA, Off New Drug Qual Assessment, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM George.lunn@fda.hhs.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-2947-1 J9 ACS SYM SER JI ACS Symp. Ser. PY 2014 VL 1147 BP 71 EP 80 PG 10 WC Chemistry, Multidisciplinary; Environmental Sciences SC Chemistry; Environmental Sciences & Ecology GA BB6EE UT WOS:000344714200005 ER PT S AU Rodriguez, JD Gryniewicz-Ruzicka, CM Arzhantsev, S Kauffman, JF Buhse, LF AF Rodriguez, Jason D. Gryniewicz-Ruzicka, Connie M. Arzhantsev, Sergey Kauffman, John F. Buhse, Lucinda F. BE Town, WG Currano, JN TI Rapid Screening Methods for Pharmaceutical Surveillance SO SCIENCE AND THE LAW: ANALYTICAL DATA IN SUPPORT OF REGULATION IN HEALTH, FOOD, AND THE ENVIRONMENT SE ACS Symposium Series LA English DT Proceedings Paper CT Symp on Science and the Law: Analytical Data in Support of Regulation in Health, Food, and the Environment / 244th Amer-Chem-Soc National Meeting and Exposition CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Chem Informat ID ION MOBILITY SPECTROMETRY; DIETARY-SUPPLEMENTS; WEIGHT-LOSS; CALCIUM SUPPLEMENTS; RAMAN-SPECTROSCOPY; SYNTHETIC ADULTERANTS; MASS-SPECTROMETRY; LEAD CONTENT; ESI-MS; SIBUTRAMINE AB Over the past few years, the United States Food and Drug Administration has developed rapid spectroscopic screening methods for the surveillance of pharmaceutical materials in the field. The main objective of this program is to enhance public safety and ensure that drug products and ingredients are safe and effective. This chapter presents a broad overview of the technologies that are used in the rapid screening program and highlights their use in improving public safety by increasing the number of regulated products that can be screened before reaching consumers. C1 [Rodriguez, Jason D.; Gryniewicz-Ruzicka, Connie M.; Arzhantsev, Sergey; Kauffman, John F.; Buhse, Lucinda F.] 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 NR 63 TC 2 Z9 2 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-2947-1 J9 ACS SYM SER JI ACS Symp. Ser. PY 2014 VL 1147 BP 149 EP 168 PG 20 WC Chemistry, Multidisciplinary; Environmental Sciences SC Chemistry; Environmental Sciences & Ecology GA BB6EE UT WOS:000344714200011 ER PT J AU Li, XF Chen, S Sun, TC Xu, YX Chen, YA Liu, YH Xiang, R Li, N AF Li, Xuefei Chen, Si Sun, Tongchao Xu, Yingxi Chen, Yanan Liu, Yanhua Xiang, Rong Li, Na TI The Transcriptional Regulation of SOX2 on FOXA1 Gene and its Application in Diagnosis of Human Breast and Lung Cancers SO CLINICAL LABORATORY LA English DT Article DE SOX2; FOXA1; breast cancer; lung cancer; tumor diagnosis ID EMBRYONAL CARCINOMA-CELLS; PROSTATE-CANCER; RECEPTOR FUNCTION; EXPRESSION; DIFFERENTIATION; ASSOCIATION; FIBROBLASTS; INHIBITOR; REPRESSES; PROGNOSIS AB Background: Recent study demonstrated the important contribution of SOX2 to tumorigenesis and metastasis properties of various types of cancers and strongly supported the concept that SOX2 can be used as an effective marker for diagnosis and predicting prognosis of cancer patients. However, our previous RNA-Seq results from human lung cancer cell line A549 showed that some oncogenes, including FOXA1 are negatively regulated by SOX2. Methods: To further verify the transcriptional regulation effect of SOX2 on FOXA1 and elucidate its application in the diagnosis of human lung and breast cancer, we performed real-time RT-PCR and Western blotting to test the regulation effect of SOX2 on the expression of FOXA1 gene. OncoPrint analysis was used to reveal the alteration of SOX2 and FOXA1 genes in breast invasive carcinoma cases and lung squamous cell carcinoma cases from the Cancer Genome Atlas (TCGA) data portal. Immunohistochemistry staining was performed to test the expression of SOX2 and FOXA1 in human breast and lung carcinoma. Results: The results showed that there is an inhibitory effect of SOX2 on the expression of FOXA1 gene. In addition, these two genes are altered in 5.8% of 484 breast invasive carcinoma cases and 46.4% of 179 lung squamous cell carcinoma cases from the Cancer Genome Atlas (TCGA) data portal, which showed an increased percentage of carcinoma cases when compared with single gene alteration. Immunohistochemistry staining of SOX2 and FOXA1 in human breast and lung carcinoma further revealed the mutual complementary effect of these two proteins in the diagnosis of carcinoma. Conclusions: Our study revealed SOX2 as a negative upstream regulator for FOXA1 gene and demonstrated SOX2 and FOXA1 as effective dual markers in improving the diagnosis efficiency for human lung and breast tumor. C1 [Li, Xuefei; Chen, Si; Sun, Tongchao; Xu, Yingxi; Chen, Yanan; Liu, Yanhua; Xiang, Rong; Li, Na] Nankai Univ, Sch Med, Tianjin 300071, Peoples R China. [Li, Xuefei] Beijing Hlth Vocat Coll, Beijing 100053, Peoples R China. [Chen, Si] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Xiang, Rong; Li, Na] Tianjin Key Lab Tumor Microenvironm & Neurovasc R, Tianjin 300071, Peoples R China. RP Li, N (reprint author), Nankai Univ, Sch Med, 94 Weijin Rd, Tianjin 300071, Peoples R China. EM lina08@nankai.edu.cn FU NSFC [31000616, 81372308]; China International Cooperation Research Program [2012DFA10650] FX This work was funded by: NSFC (31000616 and 81372308 to N. Li), China International Cooperation Research Program 2012DFA10650 (to R. Xiang). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 6 Z9 6 U1 0 U2 5 PU CLIN LAB PUBL PI HEIDELBERG PA IM BREITSPIEL 15, HEIDELBERG, D-69126, GERMANY SN 1433-6510 J9 CLIN LAB JI Clin. Lab. PY 2014 VL 60 IS 6 BP 909 EP 918 DI 10.7754/Clin.Lab.2013.130437 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AQ5OD UT WOS:000342857600005 PM 25016694 ER PT J AU Liu, Y Wu, HH Li, M Yin, JJ Nie, ZH AF Liu, Yi Wu, Haohao Li, Meng Yin, Jun-Jie Nie, Zhihong TI pH dependent catalytic activities of platinum nanoparticles with respect to the decomposition of hydrogen peroxide and scavenging of superoxide and singlet oxygen SO NANOSCALE LA English DT Article ID RESONANCE SPECTROSCOPY; OXIDE NANOPARTICLES; FUEL-CELLS; ZINC-OXIDE; GENERATION; CYTOTOXICITY; MECHANISMS; TOXICITY; RADICALS; CANCER AB Recently, platinum (Pt) nanoparticles (NPs) have received increasing attention in the field of catalysis and medicine due to their excellent catalytic activity. To rationally design Pt NPs for these applications, it is crucial to understand the mechanisms underlying their catalytic and biological activities. This article describes a systematic study on the Pt NP-catalyzed decomposition of hydrogen peroxide (H2O2) and scavenging of superoxide (O(2)c(sic)) and singlet oxygen (O-1(2)) over a physiologically relevant pH range of 1.12-10.96. We demonstrated that the catalytic activities of Pt NPs can be modulated by the pH value of the environment. Our results suggest that Pt NPs possess peroxidase-like activity of decomposing H2O2 into cOH under acidic conditions, but catalase-like activity of producing H2O and O-2 under neutral and alkaline conditions. In addition, Pt NPs exhibit significant superoxide dismutase-like activity of scavenging O-2(sic) under neutral conditions, but not under acidic conditions. The O-1(2) scavenging ability of Pt NPs increases with the increase in the pH of the environment. The study will provide useful guidance for designing Pt NPs with desired catalytic and biological properties. C1 [Liu, Yi; Nie, Zhihong] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [Liu, Yi; Wu, Haohao; Li, Meng; Yin, Jun-Jie] 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; znie@umd.edu RI Yin, Jun Jie /E-5619-2014; Nie, Zhihong/D-7495-2011; OI Nie, Zhihong/0000-0001-9639-905X; Wu, Haohao/0000-0003-3852-2608 FU FDA HHS [5U01FD001418] NR 35 TC 19 Z9 20 U1 9 U2 64 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 2014 VL 6 IS 20 BP 11904 EP 11910 DI 10.1039/c4nr03848g PG 7 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA AQ7MB UT WOS:000343000800040 PM 25175625 ER PT S AU Masci, P Zhang, Y Jones, P Oladimeji, P D'Urso, E Bernardeschi, C Curzon, P Thimbleby, H AF Masci, Paolo Zhang, Yi Jones, Paul Oladimeji, Patrick D'Urso, Enrico Bernardeschi, Cinzia Curzon, Paul Thimbleby, Harold BE Badger, JM Rozier, KY TI Combining PVSio with Stateflow SO NASA FORMAL METHODS, NFM 2014 SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 6th NASA Formal Methods Symposium (NFM) CY APR 29-MAY 01, 2014 CL NASA Johnson Space Ctr, Houston, TX HO NASA Johnson Space Ctr DE Simulation; PVSio; Stateflow AB An approach to integrating PVS executable specifications and Stateflow models is presented that uses web services to enable a seamless exchange of simulation events and data between PVS and Stateflow. Thus, it allows the wide range of applications developed in Stateflow to benefit from the rigor of PVS verification. The effectiveness of the approach is demonstrated on a medical device prototype, which consists of a user interface developed in PVS and a software controller implemented in Stateflow. Simulation on the prototype shows that simulation data produced is exchanged smoothly between in PVSio and Stateflow. C1 [Masci, Paolo; Curzon, Paul] Queen Mary Univ London, Sch Elect Engn & Comp Sci, London, England. [Zhang, Yi; Jones, Paul] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Oladimeji, Patrick; Thimbleby, Harold] Swansea Univ, FITLab, Swansea SA2 8PP, W Glam, Wales. [D'Urso, Enrico; Bernardeschi, Cinzia] Univ Pisa, Dipartimento Ingn Informaz, Pisa, Italy. RP Masci, P (reprint author), Queen Mary Univ London, Sch Elect Engn & Comp Sci, London, England. EM p.m.masci@qmul.ac.uk; yi.zhang2@fda.hhs.gov; paul.jones@fda.hhs.gov; p.oladimeji@swansea.ac.uk; e.durso@studenti.unipi.it; c.bernardeschi@unipi.it; p.curzon@qmul.ac.uk; h.thimbleby@swansea.ac.uk OI Bernardeschi, Cinzia/0000-0003-1604-4465; Masci, Paolo/0000-0002-0667-7763 FU CHI+ MED (EPSRC) [EP/ G059063/ 1] FX This work is part of CHI+ MED (EPSRC grant EP/ G059063/ 1). NR 9 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-06200-6; 978-3-319-06199-3 J9 LECT NOTES COMPUT SC PY 2014 VL 8430 BP 209 EP 214 PG 6 WC Computer Science, Software Engineering; Computer Science, Theory & Methods SC Computer Science GA BB3IX UT WOS:000342810300016 ER PT S AU Smith, RE Tran, K Richards, KM AF Smith, Robert E. Tran, Kevin Richards, Kristy M. BE AttaUrRahman, FRS TI Bioactive Annonaceous Acetogenins SO STUDIES IN NATURAL PRODUCTS CHEMISTRY, VOL 41 SE Studies in Natural Products Chemistry LA English DT Article; Book Chapter ID MITOCHONDRIAL COMPLEX-I; NADH-UBIQUINONE OXIDOREDUCTASE; TETRAHYDROFURAN RING ACETOGENINS; TANDEM MASS-SPECTROMETRY; ATYPICAL PARKINSONISM; FAMILY ANNONACEAE; DYNAMIC FUNCTION; RECENT PROGRESS; SQUAMOSA SEEDS; PAW PAW C1 [Smith, Robert E.; Tran, Kevin; Richards, Kristy M.] US FDA, Lenexa, KS 66215 USA. [Smith, Robert E.] Pk Univ, Dept Sci, Parkville, MO USA. RP Smith, RE (reprint author), US FDA, Lenexa, KS 66215 USA. NR 92 TC 9 Z9 9 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1572-5995 BN 978-0-444-63295-1; 978-0-444-63294-4 J9 STUD NAT PROD CHEM JI Stud. Nat. Prod. Chem. PY 2014 VL 41 BP 95 EP 117 DI 10.1016/B978-0-444-63294-4.00004-8 PG 23 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BB2YX UT WOS:000342571400005 ER PT S AU Snellman, E AF Snellman, E. BE Hoorfar, J TI Guidelines and protocols for safe practice in fresh produce production: FDA legislation SO GLOBAL SAFETY OF FRESH PRODUCE: A HANDBOOK OF BEST PRACTICE, INNOVATIVE COMMERCIAL SOLUTIONS AND CASE STUDIES SE Woodhead Publishing Series in Food Science Technology and Nutrition LA English DT Article; Book Chapter DE FDA; produce safety; good agricultural practices (GAPs); Coordinated Outbreak Response & Evaluation (CORE); Food Safety Modernizaton Act (FSMA) ID GREEN ONIONS; OUTBREAK AB As fresh produce consumption by US consumers increased, so too did outbreaks of illness related to consumption of those commodities. In response, the US Food and Drug Administration (FDA), together with the US Department of Agriculture (USDA), developed guidance setting out good agricultural practices (GAPs) to minimize contamination of produce, and began working with food safety partners to promote their adoption. In implementing GAPs, lessons learned during key outbreaks have led to enhanced efforts to minimize illness related to consumption of fresh produce through prevention, response, education and research. The Agency is now working to establish on-farm preventive controls that will be mandatory for many produce growers and packers. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Snellman, E (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS 317,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Erick.Snellman@fda.hhs.gov NR 28 TC 0 Z9 0 U1 1 U2 3 PU WOODHEAD PUBL LTD PI CAMBRIDGE PA ABINGTON HALL ABINGTON, CAMBRIDGE CB1 6AH, CAMBS, ENGLAND SN 2042-8049 BN 978-1-78242-027-9; 978-1-78242-018-7 J9 WOODHEAD PUBL FOOD S JI Woodhead Publ. Food Sci. Technol. Nutr. PY 2014 IS 260 BP 22 EP 32 DI 10.1533/9781782420279.1.22 PG 11 WC Agronomy; Food Science & Technology SC Agriculture; Food Science & Technology GA BB2HQ UT WOS:000341779200005 ER PT S AU Feng, P AF Feng, Peter BE Hoorfar, J TI Global safety of fresh produce A handbook of best practice, innovative commercial solutions and case studies Foreword SO GLOBAL SAFETY OF FRESH PRODUCE: A HANDBOOK OF BEST PRACTICE, INNOVATIVE COMMERCIAL SOLUTIONS AND CASE STUDIES SE Woodhead Publishing Series in Food Science Technology and Nutrition LA English DT Editorial Material; Book Chapter C1 US FDA, College Pk, MD 20740 USA. RP Feng, P (reprint author), US FDA, HFS 711,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Peter.Feng@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WOODHEAD PUBL LTD PI CAMBRIDGE PA ABINGTON HALL ABINGTON, CAMBRIDGE CB1 6AH, CAMBS, ENGLAND SN 2042-8049 BN 978-1-78242-027-9; 978-1-78242-018-7 J9 WOODHEAD PUBL FOOD S JI Woodhead Publ. Food Sci. Technol. Nutr. PY 2014 IS 260 BP XXXV EP XXXVI PG 2 WC Agronomy; Food Science & Technology SC Agriculture; Food Science & Technology GA BB2HQ UT WOS:000341779200002 ER PT S AU Luo, Y Ingram, DT Khurana, K AF Luo, Y. Ingram, D. T. Khurana, K. BE Hoorfar, J TI Preventing cross-contamination during produce wash operations SO GLOBAL SAFETY OF FRESH PRODUCE: A HANDBOOK OF BEST PRACTICE, INNOVATIVE COMMERCIAL SOLUTIONS AND CASE STUDIES SE Woodhead Publishing Series in Food Science Technology and Nutrition LA English DT Article; Book Chapter DE post-harvest; produce; wash water; sanitizers; foodborne pathogens ID ESCHERICHIA-COLI O157-H7; FRESH-CUT LETTUCE; CHLORINE INACTIVATION; WATER; DISINFECTION; VEGETABLES; SURVIVAL; EFFICACY; GROWTH AB Produce washing is a common commercial practice intended to enhance product quality and shelf-life, and improve food safety through the removal of foreign materials, plant tissue exudates and the inactivation of both human pathogens and spoilage microorganisms. However, in the absence of sufficient sanitizer presence, washing also has the potential to allow pathogen survival and spread to uncontaminated produce in the wash water. Maintenance of effective sanitizer concentrations in the wash water is a critical control point to reduce risk by preventing wash water itself from becoming a major source of pathogen cross-contamination. C1 [Luo, Y.] ARS, USDA, Environm Microbial & Food Safety Lab, Beltsville, MD 20705 USA. [Ingram, D. T.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Khurana, K.] Pulse Instruments, Camarillo, CA 93012 USA. RP Luo, Y (reprint author), ARS, USDA, Environm Microbial & Food Safety Lab, Beltsville, MD 20705 USA. EM Yaguang.Luo@ars.usda.gov; David.Ingram@fda.hhs.gov NR 22 TC 3 Z9 3 U1 0 U2 4 PU WOODHEAD PUBL LTD PI CAMBRIDGE PA ABINGTON HALL ABINGTON, CAMBRIDGE CB1 6AH, CAMBS, ENGLAND SN 2042-8049 BN 978-1-78242-027-9; 978-1-78242-018-7 J9 WOODHEAD PUBL FOOD S JI Woodhead Publ. Food Sci. Technol. Nutr. PY 2014 IS 260 BP 103 EP 111 DI 10.1533/9781782420279.2.103 PG 9 WC Agronomy; Food Science & Technology SC Agriculture; Food Science & Technology GA BB2HQ UT WOS:000341779200009 ER PT S AU Hoorfar, J Feng, P Duffy, G Malorny, B Binet, R AF Hoorfar, J. Feng, P. Duffy, G. Malorny, B. Binet, R. BE Hoorfar, J TI Bottlenecks and limitations in testing for pathogens in fresh produce SO GLOBAL SAFETY OF FRESH PRODUCE: A HANDBOOK OF BEST PRACTICE, INNOVATIVE COMMERCIAL SOLUTIONS AND CASE STUDIES SE Woodhead Publishing Series in Food Science Technology and Nutrition LA English DT Article; Book Chapter DE sampling; sample preparation; cultivation; PCR; sequencing ID ESCHERICHIA-COLI; SHIGELLA-FLEXNERI; ALFALFA SEEDS; RISK-FACTOR; SALMONELLA; OUTBREAK; SURVIVAL; FOODS; INFECTIONS; VEGETABLES AB Microbial content of produce can be impacted by sanitary conditions of the production region, use of composted manure, type and quality of irrigation water and many other factors, which can introduce risk factors. Furthermore, the types of produce, uneven distribution of contamination and heterogeneity of samples all pose challenges to obtaining representative samples. Other variables to consider when testing for pathogens in produce include method sensitivity, specificity, applicability, etc. These statistical and analytical uncertainties can have a significant impact as the data are used to infer the health risk of larger product lots, which are broadly sold and are often ready-to-eat. C1 [Hoorfar, J.] Tech Univ Denmark, DK-2860 Soborg, Denmark. [Feng, P.; Binet, R.] US FDA, College Pk, MD 20740 USA. [Duffy, G.] TEAGASC, Food Res Ctr, Dublin 15, Ireland. [Malorny, B.] BfR, Berlin, Germany. RP Feng, P (reprint author), US FDA, HFS 711,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM jhoo@food.dtu.dk; Peter.Feng@fda.hhs.gov; geraldine.duffy@teagasc.ie; burkhard.malorny@bfr.bund.de; rachel.binet@fda.hms.gov NR 47 TC 0 Z9 0 U1 0 U2 1 PU WOODHEAD PUBL LTD PI CAMBRIDGE PA ABINGTON HALL ABINGTON, CAMBRIDGE CB1 6AH, CAMBS, ENGLAND SN 2042-8049 BN 978-1-78242-027-9; 978-1-78242-018-7 J9 WOODHEAD PUBL FOOD S JI Woodhead Publ. Food Sci. Technol. Nutr. PY 2014 IS 260 BP 274 EP 291 DI 10.1533/9781782420279.4.274 PG 18 WC Agronomy; Food Science & Technology SC Agriculture; Food Science & Technology GA BB2HQ UT WOS:000341779200022 ER PT S AU Smith, MA AF Smith, M. A. BE Hoorfar, J TI Sprout-associated outbreaks and development of preventive controls SO GLOBAL SAFETY OF FRESH PRODUCE: A HANDBOOK OF BEST PRACTICE, INNOVATIVE COMMERCIAL SOLUTIONS AND CASE STUDIES SE Woodhead Publishing Series in Food Science Technology and Nutrition LA English DT Article; Book Chapter DE sprouts; sprouted seed; pathogens; outbreaks; preventive controls AB Fresh produce is an important part of a healthy diet. However, produce is susceptible to contamination. Produce is often consumed raw, or only lightly cooked, which may allow pathogens to survive and cause illness. Sprouts are especially problematic because the conditions that encourage seeds to sprout are also ideal for growth of pathogens, if present. The steps of sprout production do not include processes to eliminate pathogens. This chapter describes an iterative process to better understand hazards associated with sprouted seeds and beans, to identify preventive controls for these hazards and to monitor and promote adoption of effective preventive controls. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Smith, MA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 317, College Pk, MD 20740 USA. EM michelle.smith@fda.hhs.gov NR 18 TC 0 Z9 0 U1 1 U2 1 PU WOODHEAD PUBL LTD PI CAMBRIDGE PA ABINGTON HALL ABINGTON, CAMBRIDGE CB1 6AH, CAMBS, ENGLAND SN 2042-8049 BN 978-1-78242-027-9; 978-1-78242-018-7 J9 WOODHEAD PUBL FOOD S JI Woodhead Publ. Food Sci. Technol. Nutr. PY 2014 IS 260 BP 327 EP 339 DI 10.1533/9781782420279.5.327 PG 13 WC Agronomy; Food Science & Technology SC Agriculture; Food Science & Technology GA BB2HQ UT WOS:000341779200025 ER PT J AU Kanungo, J Cuevas, E Ali, SF Paule, MG AF Kanungo, Jyotshna Cuevas, Elvis Ali, Syed F. Paule, Merle G. TI Zebrafish Model in Drug Safety Assessment SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Zebrafish; drug; toxicity screening; high throughput assay; neurotoxicity; hepatotoxicity; cardiotoxicity ID EMBRYO TERATOGENESIS ASSAY; DANIO-RERIO EMBRYOS; METABOLIC-ACTIVATION SYSTEM; BLOOD-RETINAL BARRIER; HAIR CELL-DEATH; IN-VIVO MODEL; DEVELOPMENTAL TOXICITY; LATERAL-LINE; ETHANOL EXPOSURE; LARVAL ZEBRAFISH AB Over the past decade, zebrafish are being increasingly used in assessing the effects of chemical compounds. Especially, the embryos and larvae, due to their microscopically small size and optical transparency, are compatible with multi-well microtiter plates for high throughput screening. Being transparent, they allow for non-invasive visualization of internal organs during early development. The organization of the genome, the genetic pathways controlling signal transduction and the developmental pattern appear to be significantly conserved between zebrafish and humans. Major organ systems including the nervous, cardiovascular, digestive and visual systems of zebrafish are also similar to their mammalian counterparts at the anatomical, physiological and molecular levels. Therefore, zebrafish assays are ideal for evaluating multiple organ toxicities simultaneously that contrast in vitro assays performed on cultured cells or tissue explants and organ slices. Although research on zebrafish as a model system began a few decades ago, later studies on zebrafish developmental biology and developmental genetics resulted in the characterization of a large number of genes involved in vertebrate development and biological pathways thus establishing zebrafish as a relevant human disease model for research. Recently, zebrafish have become an attractive vertebrate model for pharmaceutical and toxicological studies. We have outlined in this review some of the toxicological screens and tools that used zebrafish early life stages, and the efforts made to validate zebrafish assays against mammalian drug screens. C1 [Kanungo, Jyotshna; Cuevas, Elvis; Ali, Syed F.; Paule, Merle G.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Kanungo, J (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jyotshnabala.kanungo@fda.hhs.gov FU National Center for Toxicological Research (NCTR)/U.S. Food and Drug Administration (FDA) FX This work was supported by the National Center for Toxicological Research (NCTR)/U.S. Food and Drug Administration (FDA). NR 268 TC 10 Z9 10 U1 9 U2 37 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2014 VL 20 IS 34 BP 5416 EP 5429 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AP3UV UT WOS:000342004400006 PM 24502596 ER PT J AU Forrey, C Saylor, DM Silverstein, JS Douglas, JF Davis, EM Elabd, YA AF Forrey, Christopher Saylor, David M. Silverstein, Joshua S. Douglas, Jack F. Davis, Eric M. Elabd, Yossef A. TI Prediction and validation of diffusion coefficients in a model drug delivery system using microsecond atomistic molecular dynamics simulation and vapour sorption analysis SO SOFT MATTER LA English DT Article ID SPIN-ECHO NMR; SMALL-PENETRANT DIFFUSION; GLASS-FORMING LIQUIDS; FREE-VOLUME THEORY; SELF-DIFFUSION; AMORPHOUS POLYMERS; PROBE DIFFUSION; GAS-DIFFUSION; HYDROCARBON POLYMERS; COMPUTER-SIMULATION AB Diffusion of small to medium sized molecules in polymeric medical device materials underlies a broad range of public health concerns related to unintended leaching from or uptake into implantable medical devices. However, obtaining accurate diffusion coefficients for such systems at physiological temperature represents a formidable challenge, both experimentally and computationally. While molecular dynamics simulation has been used to accurately predict the diffusion coefficients, D, of a handful of gases in various polymers, this success has not been extended to molecules larger than gases, e.g., condensable vapours, liquids, and drugs. We present atomistic molecular dynamics simulation predictions of diffusion in a model drug eluting system that represent a dramatic improvement in accuracy compared to previous simulation predictions for comparable systems. We find that, for simulations of insufficient duration, sub-diffusive dynamics can lead to dramatic over-prediction of D. We present useful metrics for monitoring the extent of sub-diffusive dynamics and explore how these metrics correlate to error in D. We also identify a relationship between diffusion and fast dynamics in our system, which may serve as a means to more rapidly predict diffusion in slowly diffusing systems. Our work provides important precedent and essential insights for utilizing atomistic molecular dynamics simulations to predict diffusion coefficients of small to medium sized molecules in condensed soft matter systems. C1 [Forrey, Christopher; Saylor, David M.; Silverstein, Joshua S.] US FDA, Div Chem & Mat Sci, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Douglas, Jack F.; Davis, Eric M.] NIST, Mat Sci & Engn Div, Mat Measurement Lab, Gaithersburg, MD USA. [Elabd, Yossef A.] Drexel Univ, Dept Chem & Biol Engn, Philadelphia, PA 19104 USA. RP Forrey, C (reprint author), US FDA, Div Chem & Mat Sci, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. EM christopher.forrey@fda.hhs.gov RI Elabd, Yossef/G-9866-2014 OI Elabd, Yossef/0000-0002-7790-9445 FU National Science Foundation through the NSF/FDA Scholar-in-Residence Program at the FDA [CBET-1041361] FX Simulations were made possible by access to high performance computational facilities through both the Division of Imaging and Applied Mathematics (DIAM) and the Division of Electrical and So. ware Engineering (DESE) at the FDA. The authors acknowledge the financial support of the National Science Foundation (CBET-1041361) through the NSF/FDA Scholar-in-Residence Program at the FDA that provided support for E. M. Davis and Y. A. Elabd. NR 99 TC 4 Z9 4 U1 6 U2 40 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1744-683X EI 1744-6848 J9 SOFT MATTER JI Soft Matter PY 2014 VL 10 IS 38 BP 7480 EP 7494 DI 10.1039/c4sm01297f PG 15 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Multidisciplinary; Polymer Science SC Chemistry; Materials Science; Physics; Polymer Science GA AP4VS UT WOS:000342077900006 PM 25115846 ER PT S AU Tatavarthy, A Luna, VA Amuso, PT AF Tatavarthy, Aparna Luna, Vicki A. Amuso, Philip T. BE Bush, K TI How multidrug resistance in typhoid fever affects treatment options SO ANTIMICROBIAL THERAPEUTICS REVIEWS: INFECTIOUS DISEASES OF CURRENT AND EMERGING CONCERN SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE Salmonella Typhi; typhoid fever; antibiotic resistance; fluoroquinolones ID ENTERICA SEROVAR-TYPHI; MEDIATED QUINOLONE RESISTANCE; DECREASED CIPROFLOXACIN SUSCEPTIBILITY; MULTIRESISTANT SALMONELLA-TYPHI; FIELD GEL-ELECTROPHORESIS; SEROTYPE TYPHI; CHLORAMPHENICOL RESISTANCE; MOLECULAR ANALYSIS; DRUG-RESISTANCE; UNITED-STATES AB Salmonella enterica serotype Typhi (S. Typhi) is an enteric pathogen that causes typhoid fever. The infection can be severe, with significant morbidity and mortality, requiring antimicrobial therapy. Cases of S. Typhi infection in the United States and other developed countries are often associated with travel to endemic regions. The empirical use of first-line drugs for therapy, including ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole, has resulted in transmissible multidrug resistance. With the global increase in multidrug-resistant S. Typhi, use of ciprofloxacin, with excellent oral absorption, few side effects, and cost-effectiveness, has become popular for treatment. However, decreased ciprofloxacin susceptibility due to point mutations in the S. Typhi genes gyrA and/or parC has caused treatment failures, necessitating alternative therapeutic options. S. Typhi is typically genetically homogenous, with phylogenetic and epidemiological studies showing that identical clones and diverse S. Typhi types often coexist in the same geographic region. Studies investigating point mutations have demonstrated that selective pressure from empirical use of first-line drugs and fluoroquinolones has led to the global emergence of haplotype H-58. Antibiotic resistance is subject to high selective pressure in S. Typhi and thus demands careful use of antimicrobials. C1 [Tatavarthy, Aparna; Luna, Vicki A.] Univ S Florida, Coll Publ Hlth, Ctr Biol Def, Tampa, FL USA. [Amuso, Philip T.] Florida Dept Hlth, Bur Publ Hlth Labs, Tampa, FL USA. [Amuso, Philip T.] Univ S Florida, Morsani Coll Med, Tampa, FL USA. RP Tatavarthy, A (reprint author), US FDA, Dept Hlth & Human Serv HHS, CFSAN, ORS, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Aparna.Tatavarthy@fda.hhs.gov NR 100 TC 3 Z9 4 U1 1 U2 5 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 2014 VL 1323 BP 76 EP 90 DI 10.1111/nyas.12490 PG 15 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA BB1PH UT WOS:000341250600007 PM 25069595 ER PT B AU Yang, X Schnackenberg, LK Shi, Q Salminen, WF AF Yang, Xi Schnackenberg, Laura K. Shi, Qiang Salminen, William F. BE Gupta, RC TI Hepatic toxicity biomarkers SO BIOMARKERS IN TOXICOLOGY LA English DT Article; Book Chapter ID INDUCED LIVER-INJURY; ACETAMINOPHEN-INDUCED HEPATOTOXICITY; MITOCHONDRIAL PERMEABILITY TRANSITION; PERFORMANCE LIQUID-CHROMATOGRAPHY; GAMMA-GLUTAMYL-TRANSPEPTIDASE; GLUTATHIONE S-TRANSFERASE; CIRCULATING MICRORNAS; QUANTITATIVE-ANALYSIS; METABOLIC-ACTIVATION; SERUM BIOMARKERS C1 [Yang, Xi; Schnackenberg, Laura K.; Shi, Qiang] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Salminen, William F.] PAREXEL, Sarasota, FL USA. RP Yang, X (reprint author), US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 164 TC 1 Z9 1 U1 0 U2 2 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-404649-8; 978-0-12-404630-6 PY 2014 BP 241 EP 259 DI 10.1016/B978-0-12-404630-6.00013-0 PG 19 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BB1MX UT WOS:000341214100014 ER PT B AU Hilmas, CJ Fabricant, DS AF Hilmas, Corey J. Fabricant, Daniel S. BE Gupta, RC TI Biomarkers of toxicity for dietary ingredients contained in dietary supplements SO BIOMARKERS IN TOXICOLOGY LA English DT Article; Book Chapter ID CHINESE HERBS NEPHROPATHY; ARISTOLOCHIC ACID NEPHROPATHY; USNIC-ACID; RENAL-FAILURE; THYROTOXICOSIS; OUTBREAK; HEPATOTOXICITY; RATS; IDENTIFICATION; METABOLITES C1 [Hilmas, Corey J.] US FDA, Dietary Supplements Regulat Implementat Branch, Div Dietary Supplement Programs, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Fabricant, Daniel S.] US FDA, Div Dietary Supplement Programs, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Hilmas, CJ (reprint author), US FDA, Dietary Supplements Regulat Implementat Branch, Div Dietary Supplement Programs, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 69 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 978-0-12-404649-8; 978-0-12-404630-6 PY 2014 BP 609 EP 627 DI 10.1016/B978-0-12-404630-6.00035-X PG 19 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BB1MX UT WOS:000341214100036 ER PT B AU Chen, JJ Lin, WJ Lu, TP AF Chen, James J. Lin, Wei-Jiun Lu, Tzu-Pin BE Gupta, RC TI Biomarkers of susceptibility Pharmacogenomics and toxicogenomics SO BIOMARKERS IN TOXICOLOGY LA English DT Article; Book Chapter ID HIGH-DIMENSIONAL DATA; GENE-EXPRESSION DATA; MOLECULAR NUTRITION; MICROARRAY DATA; BREAST-CANCER; CLASSIFICATION; CLASSIFIERS; SELECTION; TOXICITY; LIMITATIONS C1 [Chen, James J.] US FDA, Biostat Branch, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Lin, Wei-Jiun] Feng Chia Univ, Dept Appl Math, Taipei, Taiwan. [Lu, Tzu-Pin] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Chen, JJ (reprint author), US FDA, Biostat Branch, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. OI LU, TZU-PIN/0000-0003-3697-0386 NR 33 TC 0 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-404649-8; 978-0-12-404630-6 PY 2014 BP 975 EP 982 DI 10.1016/B978-0-12-404630-6.00058-0 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BB1MX UT WOS:000341214100059 ER PT B AU Farrar, JA Guzewich, J AF Farrar, Jeffrey A. Guzewich, Jack BE Matthews, KR Sapers, GM Gerba, CP TI Identification of the Source of Contamination SO PRODUCE CONTAMINATION PROBLEM: CAUSES AND SOLUTIONS, 2ND EDITION SE Food Science and Technology-International Series LA English DT Article; Book Chapter C1 [Farrar, Jeffrey A.; Guzewich, Jack] US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. RP Farrar, JA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-404686-3; 978-0-12-404611-5 J9 FOOD SCI TECH-INT SE PY 2014 BP 59 EP 83 DI 10.1016/B978-0-12-404611-5.00003-8 PG 25 WC Food Science & Technology SC Food Science & Technology GA BB1KM UT WOS:000341162000004 ER PT B AU Keller, SE AF Keller, Susanne E. BE Matthews, KR Sapers, GM Gerba, CP TI Tree Fruits and Nuts: Outbreaks, Contamination Sources, Prevention, and Remediation SO PRODUCE CONTAMINATION PROBLEM: CAUSES AND SOLUTIONS, 2ND EDITION SE Food Science and Technology-International Series LA English DT Article; Book Chapter ID ESCHERICHIA-COLI O157-H7; UNPASTEURIZED APPLE CIDER; GOLDEN-DELICIOUS APPLES; SALMONELLA-TYPHIMURIUM DT104; ENTERITIDIS PHAGE TYPE-30; LISTERIA-MONOCYTOGENES; FRESH PRODUCE; UNITED-STATES; ACID TOLERANCE; ORANGE JUICE C1 FDA, CFSAN, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. RP Keller, SE (reprint author), FDA, CFSAN, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. NR 152 TC 2 Z9 2 U1 1 U2 6 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-404686-3; 978-0-12-404611-5 J9 FOOD SCI TECH-INT SE PY 2014 BP 291 EP 312 DI 10.1016/B978-0-12-404611-5.00013-0 PG 22 WC Food Science & Technology SC Food Science & Technology GA BB1KM UT WOS:000341162000014 ER PT B AU Prestin, A Chou, WYS AF Prestin, Abby Chou, Wen-ying Sylvia BE Hamilton, HE Chou, WYS TI Web 2.0 and the changing health communication environment SO ROUTLEDGE HANDBOOK OF LANGUAGE AND HEALTH COMMUNICATION SE Routledge Handbooks in Applied Linguistics LA English DT Article; Book Chapter ID NATIONAL TRENDS SURVEY; DIGITAL DIVIDE; BREAST-CANCER; SUPPORT GROUP; SOCIAL MEDIA; INFORMATION; INTERNET; ONLINE; FACEBOOK; YOUTUBE C1 [Prestin, Abby] US FDA, Ctr Tobacco Prod, Rockville, MD 20857 USA. [Chou, Wen-ying Sylvia] NCI, Hlth Commun & Informat Res Branch, Bethesda, MD 20892 USA. RP Prestin, A (reprint author), US FDA, Ctr Tobacco Prod, Rockville, MD 20857 USA. NR 61 TC 1 Z9 1 U1 1 U2 1 PU ROUTLEDGE PI ABINGDON PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND BN 978-1-315-85697-1; 978-0-415-67043-2 J9 ROUT HANDB APPL PY 2014 BP 184 EP 197 PG 14 WC Health Policy & Services; Linguistics SC Health Care Sciences & Services; Linguistics GA BB1JD UT WOS:000341147600013 ER PT J AU Binkowitz, B Yue, LQ AF Binkowitz, Bruce Yue, Lilly Q. TI SPECIAL ISSUE ASSOCIATED WITH THE 2013 ASA BIOPHARMACEUTICAL FDA/INDUSTRY STATISTICS WORKSHOP SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Editorial Material C1 [Binkowitz, Bruce] Merck & Co Inc, Rahway, NJ 07065 USA. [Yue, Lilly Q.] US FDA, Silver Spring, MD USA. RP Binkowitz, B (reprint author), Merck & Co Inc, Rahway, NJ 07065 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2014 VL 24 IS 5 SI SI BP 965 EP 967 DI 10.1080/10543406.2014.942425 PG 3 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA AN2MF UT WOS:000340418700001 PM 25014118 ER PT J AU Yue, LQ Lu, N Xu, YL AF Yue, Lilly Q. Lu, Nelson Xu, Yunling TI DESIGNING PREMARKET OBSERVATIONAL COMPARATIVE STUDIES USING EXISTING DATA AS CONTROLS: CHALLENGES AND OPPORTUNITIES SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Observational comparative studies; Propensity score; Study design; Use of existing data ID PROPENSITY SCORES; CAUSAL INFERENCE; BIAS AB Due to the special nature of medical device clinical studies, observational (nonrandomized) comparative studies play important roles in the premarket safety/effectiveness evaluation of medical devices. While historical data collected in earlier investigational device exemption studies of a previously approved medical device have been used to form control groups in comparative studies, high-quality registry data are emerging to provide opportunities for the premarket evaluation of new devices. However, in such studies, various biases could be introduced in every stage and aspect of study and may compromise the objectivity of study design and validity of study results. In this article, challenges and opportunities in the design of such studies using propensity score methodology are discussed from regulatory perspectives. C1 [Yue, Lilly Q.; Lu, Nelson; Xu, Yunling] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Yue, LQ (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM lilly.yue@fda.hhs.gov NR 19 TC 3 Z9 3 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2014 VL 24 IS 5 SI SI BP 994 EP 1010 DI 10.1080/10543406.2014.926367 PG 17 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA AN2MF UT WOS:000340418700004 PM 25013971 ER PT J AU Hung, HMJ Wang, SJ Yang, PL AF Hung, H. M. James Wang, Sue-Jane Yang, Peiling TI SOME CHALLENGES WITH STATISTICAL INFERENCE IN ADAPTIVE DESIGNS SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Adaptive selection; Adaptive statistical information; Biomarker; Marker; Unweighted Z statistic; Weighted Z statistic ID GROUP SEQUENTIAL DESIGNS; CLINICAL-TRIAL DESIGN; SAMPLE-SIZE; CONDITIONAL POWER; I ERROR; ENRICHMENT; INFORMATION; ADAPTATION; STRATEGIES; SELECTION AB Adaptive designs have generated a great deal of attention to clinical trial communities. The literature contains many statistical methods to deal with added statistical uncertainties concerning the adaptations. Increasingly encountered in regulatory applications are adaptive statistical information designs that allow modification of sample size or related statistical information and adaptive selection designs that allow selection of doses or patient populations during the course of a clinical trial. For adaptive statistical information designs, a few statistical testing methods are mathematically equivalent, as a number of articles have stipulated, but arguably there are large differences in their practical ramifications. We pinpoint some undesirable features of these methods in this work. For adaptive selection designs, the selection based on biomarker data for testing the correlated clinical endpoints may increase statistical uncertainty in terms of type I error probability, and most importantly the increased statistical uncertainty may be impossible to assess. C1 [Hung, H. M. James; Yang, Peiling] US FDA, Div Biometr 1, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Wang, Sue-Jane] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Hung, HMJ (reprint author), US FDA, Div Biometr 1, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 21,Room 4616, Silver Spring, MD 20993 USA. EM hsienming.hung@fda.hhs.gov FU RSR fund by Center for Drug Evaluation and Research of the U.S. Food and Drug Administration [05-02] FX The research work presented in this article was supported by the RSR fund number 05-02, provided by Center for Drug Evaluation and Research of the U.S. Food and Drug Administration. NR 37 TC 5 Z9 5 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2014 VL 24 IS 5 SI SI BP 1059 EP 1072 DI 10.1080/10543406.2014.925911 PG 14 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA AN2MF UT WOS:000340418700008 PM 24915027 ER PT J AU Chen, Y Luo, S Chu, HT Su, X Nie, L AF Chen, Yong Luo, Sheng Chu, Haitao Su, Xiao Nie, Lei TI An Empirical Bayes Method for Multivariate Meta-analysis with an Application in Clinical Trials SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE Bivariate beta-binomial model; Exact method; Hypergeometric function; Meta-analysis; Relative risk; Sarmanov family ID BIVARIATE DISTRIBUTIONS; DIABETES-MELLITUS; SARMANOV FAMILY; WOMEN; MODEL; RISK; SPECIFICITY; SENSITIVITY; PREVALENCE AB We propose an empirical Bayes method for evaluating overall and study-specific treatment effects in multivariate meta-analysis with binary outcome. Instead of modeling transformed proportions or risks via commonly used multivariate general or generalized linear models, we directly model the risks without any transformation. The exact posterior distribution of the study-specific relative risk is derived. The hyperparameters in the posterior distribution can be inferred through an empirical Bayes procedure. As our method does not rely on the choice of transformation, it provides a flexible alternative to the existing methods and in addition, the correlation parameter can be intuitively interpreted as the correlation coefficient between risks. C1 [Chen, Yong; Luo, Sheng; Su, Xiao] 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] US FDA, Div Biometr 4, Off Biometr, OTS,CDER, Silver Spring, MD 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 Agency for Healthcare Research and Quality [R03HS022900]; National Institutes of Health/National Center for Advancing Translational Sciences [KL2 TR000370]; U.S. Department of Health and Human Services Agency for Healthcare Research and Quality Grant from the U.S. National Cancer Institute [R03HS020666, P01CA142538] FX Yong Chen was supported by grant number R03HS022900 from the Agency for Healthcare Research and Quality. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality. Sheng Luo's research was supported in part by National Institutes of Health/National Center for Advancing Translational Sciences grant KL2 TR000370. Haitao Chu was supported in part by the U.S. Department of Health and Human Services Agency for Healthcare Research and Quality Grant R03HS020666 and P01CA142538 from the U.S. National Cancer Institute". NR 35 TC 0 Z9 0 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0361-0926 EI 1532-415X J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PY 2014 VL 43 IS 16 BP 3536 EP 3551 DI 10.1080/03610926.2012.700379 PG 16 WC Statistics & Probability SC Mathematics GA AN0LW UT WOS:000340277100012 PM 25089070 ER PT J AU Andersen, ME Betts, K Dragan, Y Fitzpatrick, S Goodman, JL Hartung, T Himmelfarb, J Ingber, DE Jacobs, A Kavlock, R Kolaja, K Stevens, JL Tagle, D Taylor, DL Throckmorton, D AF Andersen, Melvin E. Betts, Kellyn Dragan, Yvonne Fitzpatrick, Suzanne Goodman, Jesse L. Hartung, Thomas Himmelfarb, Jonathan Ingber, Donald E. Jacobs, Abigail Kavlock, Robert Kolaja, Kyle Stevens, James L. Tagle, Dan Taylor, D. Lansing Throckmorton, Douglas TI Developing Microphysiological Systems for Use as Regulatory Tools - Challenges and Opportunities SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION LA English DT Editorial Material ID CHIP C1 [Andersen, Melvin E.] Hamner Inst Hlth Sci, Res Triangle Pk, NC USA. [Dragan, Yvonne] AstraZeneca, Waltham, MA USA. [Fitzpatrick, Suzanne] US FDA, Ctr Food Safety & Appl Nutr, Silver Spring, MD USA. [Goodman, Jesse L.] US FDA, Silver Spring, MD USA. [Hartung, Thomas] Johns Hopkins Univ, Ctr Alternat Anim Testing, Baltimore, MD USA. [Himmelfarb, Jonathan] Univ Washington, Kidney Res Inst, Seattle, WA USA. [Ingber, Donald E.] Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA. [Jacobs, Abigail; Throckmorton, Douglas] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Kavlock, Robert] US EPA, Res Triangle Pk, NC USA. [Kolaja, Kyle] Cellular Dynamics Int Inc, Madison, WI USA. [Stevens, James L.] Lilly Res Labs, Greenfield, IN 46140 USA. [Tagle, Dan] Natl Ctr Adv Translat Sci, NIH, Bethesda, MD USA. [Taylor, D. Lansing] Univ Pittsburgh, Drug Discovery Inst, Pittsburgh, PA USA. RP Betts, K (reprint author), 8023 Glenside Dr, Takoma Pk, MD USA. EM k_betts@nasw.org OI Andersen, Melvin/0000-0002-3894-4811 FU NCATS NIH HHS [U18 TR000547, UH3 TR000504, UH2 TR000504] NR 6 TC 10 Z9 10 U1 2 U2 5 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 2014 VL 31 IS 3 BP 364 EP 367 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AL9NU UT WOS:000339468800012 PM 25061900 ER PT J AU Shukla, C Bashaw, ED Stagni, G Benfeldt, E AF Shukla, C. Bashaw, E. D. Stagni, G. Benfeldt, E. TI Applications of dermal microdialysis: a review SO JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY LA English DT Review DE Sampling; Kinetics; Flow rate; Dialysate; Permeation ID IN-VIVO MICRODIALYSIS; ATOPIC-DERMATITIS PATIENTS; SUCTION BLISTER TECHNIQUE; ZERO-NET-FLUX; CUTANEOUS MICRODIALYSIS; TRANSDERMAL DELIVERY; HUMAN SKIN; IONTOPHORETIC ADMINISTRATIONS; DERMATOPHARMACOKINETIC METHOD; SUBCUTANEOUS MICRODIALYSIS AB Microdialysis (MD) is a sampling technique used to assess tissue concentrations of analytes producing a real-time dynamic drug profile. It's been almost 25 years since MD saw application in sampling and measuring skin concentrations following topical and transdermal applications. The purpose of this review is to provide a technical overview of MD and summarize the widespread applications that are explored with dermal or cutaneous MD ranging from a potential tool to establish topical bioequivalence to unraveling the mechanisms of inflammatory skin disorders. This review also includes current regulatory perspectives in order to benefit scientists and/or clinicians who are novices in this area. C1 [Shukla, C.; Bashaw, E. D.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Stagni, G.] Long Isl Univ, Arnold & Marie Schwartz Coll Pharm & Hlth Sci, Div Pharmaceut Sci, Brooklyn, NY 11201 USA. [Benfeldt, E.] Univ Copenhagen, Roskilde Hosp, Dept Dermatol, Roskilde, Denmark. RP Shukla, C (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Chinmay.Shukla@fda.hhs.gov NR 122 TC 0 Z9 0 U1 3 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1773-2247 J9 J DRUG DELIV SCI TEC JI J. Drug Deliv. Sci. Technol. PY 2014 VL 24 IS 3 BP 259 EP 269 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AM5VK UT WOS:000339928900004 ER PT S AU Sandbulte, MR Eichelberger, MC AF Sandbulte, Matthew R. Eichelberger, Maryna C. BE Spackman, E TI Analyzing Swine Sera for Functional Antibody Titers Against Influenza A Neuraminidase Proteins Using an Enzyme-Linked Lectin Assay (ELLA) SO ANIMAL INFLUENZA VIRUS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Swine influenza A virus; Neuraminidase; Neuraminidase inhibition; Antibody titration ID DIVALENT-CATION REQUIREMENTS; VIRUS INFECTION; HEMAGGLUTININ; EVOLUTION; ANTIGENS; VACCINE; H1N1; MICE AB Neuraminidase (NA) is an envelope glycoprotein of influenza viruses, including swine-lineage influenza A viruses. NA possesses sialidase activity, which is functionally important at multiple points in viral replication, counter-balancing the sialic acid receptor binding activity of the hemagglutinin (HA), the other major envelope glycoprotein. The NA proteins of influenza A viruses have been classified into nine serological subtypes, and they undergo antigenic drift variation similar to that of HA. Antibodies to NA are analyzed much less often than antibodies to HA. The conventional assay for NA inhibition (NI) antibody titration, established decades ago, is widely considered unwieldy and inefficient for routine use. In recent years, a few new formats have been developed which still measure inhibition of NA enzymatic function, but more efficiently and with less chemical waste produced. Described here is the enzyme-linked lectin assay (ELLA), which is performed in 96-well plates and analyzed on a spectrophotometric plate reader. An important factor in adoption of the ELLA technique for animal studies, such as swine, is the choice of NA antigen, which may be purified protein or whole virus containing an antigenically irrelevant HA protein. This NI assay, in conjunction with the hemagglutination inhibiting (HI) antibody assay, offers a practical way to characterize viral isolates more fully and to quantify antibodies induced by infection or vaccination. C1 [Sandbulte, Matthew R.] Iowa State Univ, Coll Vet Med, Dept Vet Microbiol & Prevent Med, Ames, IA 50011 USA. [Eichelberger, Maryna C.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Sandbulte, MR (reprint author), Iowa State Univ, Coll Vet Med, Dept Vet Microbiol & Prevent Med, Ames, IA 50011 USA. NR 18 TC 3 Z9 3 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0758-8; 978-1-4939-0757-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1161 BP 337 EP 345 DI 10.1007/978-1-4939-0758-8_28 D2 10.1007/978-1-4939-0758-8 PG 9 WC Agriculture, Dairy & Animal Science; Biochemical Research Methods; Biochemistry & Molecular Biology SC Agriculture; Biochemistry & Molecular Biology GA BA8RU UT WOS:000338513600029 PM 24899442 ER PT B AU Brar, SS Gobburu, J AF Brar, Satjit S. Gobburu, Joga BE Figg, WD McLeod, HL TI Pharmacometrics SO HANDBOOK OF ANTICANCER PHARMACOKINETICS AND PHARMACODYNAMICS, 2ND EDITION SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter DE Pharmacokinetics; Pharmacodynamics; Regulatory; Drug development; Clinical pharmacology ID CLINICAL-TRIAL DESIGN; LUNG-CANCER PATIENTS; DRUG DEVELOPMENT; PHARMACODYNAMIC PRINCIPLES; MYCOPHENOLATE-MOFETIL; DISEASE PROGRESSION; LABELING DECISIONS; PREDICTIVE CHECK; DOSE SELECTION; TIME-COURSE AB Pharmacometrics is the science of quantifying disease, drug, and trial characteristics with the goal of influencing drug development and regulatory and therapeutic decisions. Techniques employing pharmacometric principles are increasingly being used, allowing for efficient utilization of prior experimental information and ultimately streamlining drug development. Using mathematical and statistical models, modeling and simulation allows a simplification of complex systems under investigation and may be able to predict the effects of various treatment options, and the corresponding consequence, on the future course of the disease process. The summation of information can be used to develop more efficient, and hopefully successful, clinical trials. This chapter summarizes the basic theory and application of pharmacometric techniques. Examples of where such pharmacometric principles have been successfully employed in oncology drug development are presented. C1 [Brar, Satjit S.; Gobburu, Joga] US FDA, Off Clin Pharmacol, Div Pharmacometr, Silver Spring, MD 20993 USA. [Gobburu, Joga] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. [Gobburu, Joga] US FDA, Silver Spring, MD USA. RP Gobburu, J (reprint author), US FDA, Off Clin Pharmacol, Div Pharmacometr, Silver Spring, MD 20993 USA. EM Satjit.Brar@fda.hhs.gov; jgobburu@rx.umaryland.edu NR 50 TC 1 Z9 1 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4614-9135-4; 978-1-4614-9134-7 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2014 BP 173 EP 192 DI 10.1007/978-1-4614-9135-4_11 D2 10.1007/978-1-4614-9135-4 PG 20 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BA6CE UT WOS:000337095300011 ER PT B AU Rahman, A AF Rahman, Atiqur BE Figg, WD McLeod, HL TI Exposure-Response Relationships of Anticancer Agents: Application in Drug Development and Drug Label SO HANDBOOK OF ANTICANCER PHARMACOKINETICS AND PHARMACODYNAMICS, 2ND EDITION SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter DE Biomarkers; Exposure; Oncology; Pharmacokinetics; Pharmacodynamics; Response; Surrogates ID PROSTATE-SPECIFIC ANTIGEN; CHRONIC MYELOID-LEUKEMIA; FLUORO-BETA-ALANINE; DOSE-RANGING TRIAL; CELL LUNG-CANCER; PHASE-I; BREAST-CANCER; TYROSINE KINASE; ZOLEDRONIC ACID; BCR-ABL AB The understanding of exposure-response relationship (ER) is critical in oncology drug development and drug approval. The ER relationship not only helps in selecting the optimum dose and regimen for testing in the pivotal clinical trial for approval, but allows recommending dose adjustment for patients with special conditions. The exposure variables are mostly area under the concentration-time profile (AUC) and/or plasma or serum concentration, while the response variable ranges from biomarkers to clinical endpoints. Application of ER assessment in oncology drug development is illustrated using approved cancer drugs, such as busulfan, zolandronic acid, imatinib, docetaxel, carboplatin, vandetanib, everolimus, and ipilimumab. The FDA guidance on ER relationships elaborates on the regulatory applications, study design, and data analysis aspects of the clinical trials that should be conducted during drug development. The results of the clinical trials exploring ER relationships are usually described in the "Clinical Pharmacology" section of the drug's package inserts; however, the impact and interpretation of the results of these trials reflecting in dose modifications, therapeutic drug monitoring, and safety are included in "Highlights," " Dosage and Administration," and "Warnings and Precautions" sections of the label. C1 US FDA, Div Clin Pharmacol 5, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Rahman, A (reprint author), US FDA, Div Clin Pharmacol 5, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Bldg 51,Room 2188,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM namatiqur.rahman@fda.hhs.gov NR 57 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4614-9135-4; 978-1-4614-9134-7 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2014 BP 747 EP 762 DI 10.1007/978-1-4614-9135-4_37 D2 10.1007/978-1-4614-9135-4 PG 16 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BA6CE UT WOS:000337095300037 ER PT J AU Kaplan, GG Konduru, K Manangeeswaran, M Jacques, J Amharref, N Nakamura, S AF Kaplan, Gerardo G. Konduru, Krishnamurthy Manangeeswaran, Mohanraj Jacques, Jerome Amharref, Nadia Nakamura, Siham BE Thomas, HC Lok, ASF Locarnini, SA Zuckerman, AJ TI Structure, molecular virology, natural history, and experimental models SO VIRAL HEPATITIS, 4TH EDITION LA English DT Article; Book Chapter ID HEPATITIS-A-VIRUS; MONKEY KIDNEY-CELLS; CAP-INDEPENDENT TRANSLATION; IRES-DEPENDENT TRANSLATION; HAVCR1 GENE HAPLOTYPES; TRACT-BINDING-PROTEIN; SUBVIRAL PARTICLES; VIRAL-RNA; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; MONOCLONAL-ANTIBODIES AB Hepatitis A virus (HAV), a small, naked, single-stranded, positive RNA virus that belongs to the Picornaviridae, causes acute hepatitis in humans and nonhuman primates. HAV infection typically does not induce cytopathic effect in cell culture, and disease results from an immunopathogenic process that clears the virus without leaving chronic sequelae. HAV is transmitted through the oral-fecal route, but it is unknown how it reaches the liver. The pathogenic process of HAV is poorly understood. However, recent advances in the understanding of the effects of the interaction of HAV with its cellular receptor 1 (HAVCR1), which blocks the activation of T cell receptors and shuts off regulatory T cell (Treg) functions, help explain how HAV modulates the immune response to evade detection during its long incubation period and is cleared with limited liver damage. The shut-off of Treg functions may also explain the protective effect of HAV infection in the development of atopy and autoimmunity. C1 [Kaplan, Gerardo G.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Konduru, Krishnamurthy] US FDA, Ctr Biol Evaluat & Res, Lab Emerging Pathogens, Bethesda, MD USA. [Manangeeswaran, Mohanraj; Jacques, Jerome; Amharref, Nadia; Nakamura, Siham] US FDA, Ctr Biol Evaluat & Res, ORISE, Res Participat Program, Bethesda, MD USA. RP Kaplan, GG (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 99 TC 0 Z9 0 U1 1 U2 5 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-67295-2 PY 2014 BP 29 EP 42 PG 14 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA BA5VL UT WOS:000337034100004 ER PT S AU Jia, YP Pereira, CP Buehler, PW AF Jia, Yiping Pereira, Claudia P. Buehler, Paul W. BE Ferreira, GC Kadish, KM Smith, KM Guilard, R TI Hemoglobin and Hemoglobin-based Oxygen Carriers: A Biochemical, Pharmacological, and Toxicological Perspective SO HANDBOOK OF PORPHYRIN SCIENCE WITH APPLICATIONS TO CHEMISTRY, PHYSICS, MATERIALS SCIENCE, ENGINEERING, BIOLOGY AND MEDICINE, VOL 27: ERYTHROPOIESIS, HEME AND APPLICATIONS TO BIOMEDICINE SE Handbook of Porphyrin Science LA English DT Article; Book Chapter ID CROSS-LINKED HEMOGLOBIN; TRAUMATIC BRAIN-INJURY; CLAM LUCINA-PECTINATA; CELL-FREE HEMOGLOBIN; RED-BLOOD-CELLS; STROMA-FREE HEMOGLOBIN; SPERM-WHALE MYOGLOBIN; NITRIC-OXIDE BINDING; CHEMICALLY-MODIFIED HEMOGLOBINS; EMBRYONIC CHICKEN HEMOGLOBINS C1 [Jia, Yiping; Pereira, Claudia P.; Buehler, Paul W.] Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Div Hematol, Bethesda, MD 20892 USA. RP Jia, YP (reprint author), Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Div Hematol, Bethesda, MD 20892 USA. EM paul.buehler@fda.hhs.gov NR 250 TC 0 Z9 0 U1 0 U2 3 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE SN 1793-9518 BN 978-981-4407-78-6 J9 HANDB PORPHYR SCI PY 2014 VL 27 BP 117 EP 165 PG 49 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA5QY UT WOS:000336962200006 ER PT S 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 BE Whiting, BR Hoeschen, C Kontos, D TI Volume estimation of multi-density nodules with thoracic CT SO MEDICAL IMAGING 2014: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging - Physics of Medical Imaging CY FEB 17-20, 2014 CL San Diego, CA SP Soc Photo Opt Instrumentat Engn, Modus Med Devices Inc, XIFIN Inc, Ventana Med Syst Inc, Intrace Med, Caresteam, GE Healthcare DE volume estimation; multi-density nodules; thoracic computed tomography; phantom study ID PULMONARY NODULES; LUNG; PHANTOM AB The purpose of this work was to quantify the effect of surrounding density on the volumetric assessment of lung nodules in a phantom CT study. Eight synthetic multi-density nodules were manufactured by enclosing spherical cores in larger spheres of double the diameter and with a different uniform density. Different combinations of outer/inner diameters (20/10mm, 10/5mm) and densities (100HU/-630H1J, 10HU/-630HU, -630HU/100HU, -630HU/-10HU) were created. The nodules were placed within an anthropomorphic phantom and scanned with a 16-detector row CT scanner. Ten repeat scans were acquired using exposures of 20, 100, and 200mAs, slice collimations of 16x0.75mm and 16x1.5mm, and pitch of 1.2, and were reconstructed with varying slice thicknesses (three for each collimation) using two reconstruction filters (medium and standard). The volumes of the inner nodule cores were estimated from the reconstructed CT data using a matched-filter approach with templates modeling the characteristics of the multi-density objects. Volume estimation of the inner nodule was assessed using percent bias (PB) and the standard deviation of percent error (SPE). The true volumes of the inner nodules were measured using micro CT imaging. Results show PB values ranging from -12.4 to 2.3% and SPE values ranging from 1.8 to 12.8%. This study indicates that the volume of multi-density nodules can be measured with relatively small percent bias (on the order of +/- 12% or less) when accounting for the properties of surrounding densities. These findings can provide valuable information for understanding bias and variability in clinical measurements of nodules that also include local biological changes such as inflammation and necrosis. C1 [Gavrielides, Marios A.; Li, Qin; Zeng, Rongping; Myers, Kyle J.; Sahiner, Berkman; Petrick, Nicholas] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Gavrielides, MA (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. 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 978-0-8194-9826-7 J9 PROC SPIE PY 2014 VL 9033 AR 903331 DI 10.1117/12.2043833 PG 10 WC Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BA8VD UT WOS:000338775800104 ER PT S AU Ghammraoui, B Peng, R Suarez, I Bettolo, C Badal, A AF Ghammraoui, B. Peng, R. Suarez, I Bettolo, C. Badal, A. BE Whiting, BR Hoeschen, C Kontos, D TI Including the effect of molecular interference in the coherent x-ray scattering modeling in MC-GPU and PENELOPE for the study of novel breast imaging modalities SO MEDICAL IMAGING 2014: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging - Physics of Medical Imaging CY FEB 17-20, 2014 CL San Diego, CA SP Soc Photo Opt Instrumentat Engn, Modus Med Devices Inc, XIFIN Inc, Ventana Med Systems Inc, Intrace Med, Caresteam, GE Healthcare DE Coherent-scatter; X-ray scattering; Monte Carlo simulation; Breast cancer; Energy Dispersive X-Ray Diffraction ID TISSUE; DIFFRACTION AB Purpose: To present upgraded versions of MC-GPU and PenEASY_Imaging, two open-source Monte Carlo codes for the simulation of radiographic projections and CT. The codes have been extended with the aim of studying breast imaging modalities that rely on the accurate modeling of coherent x-ray scatter. Methods: The simulation codes were extended to account for the effect of molecular interference in coherent scattering using experimentally measured molecular interference functions. The validity of the new model was tested experimentally using the Energy Dispersive X-Ray Diffraction (EDXRD) technique with a polychromatic x-ray source and an energy-resolved Germanium detector at a fixed scattering angle. Experiments and simulations of a full field digital mammography system with and without a ID focused antiscatter grid were conducted for additional validation. The modified MC-GPU code was also used to examine the possibility of characterizing breast cancer within a mathematical breast phantom using the EDXRD technique. Results: The measured EDXRD spectra were correctly reproduced by the simulation with the modified code while the previous code using the Independent Atomic Approximation led to large errors in the predicted diffraction spectra. There was good agreement between the simulated and measured rejection factor for the ID focused antiscatter grid with both models. The simulation study in a whole breast showed that the x-ray scattering profiles of adipose, fibrosis, cancer and benign tissues are differentiable. Conclusion: MC-GPU and PENELOPE were successfully extended and validated for accurate modeling of coherent x-ray scatter. The EDXRD technique with pencil-cone geometry in a whole breast was investigated by a simulation study and it was concluded that this technique has potential to characterize breast cancer lesions. C1 [Ghammraoui, B.; Peng, R.; Suarez, I; Bettolo, C.; Badal, A.] US FDA, Div Imaging & Appl Math, OSEL, CDRH, Silver Spring, MD 20993 USA. RP Ghammraoui, B (reprint author), US FDA, Div Imaging & Appl Math, OSEL, CDRH, Silver Spring, MD 20993 USA. EM bahaa.ghammraoui@fda.hhs.gov NR 13 TC 1 Z9 1 U1 0 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 978-0-8194-9826-7 J9 PROC SPIE PY 2014 VL 9033 AR 90334N DI 10.1117/12.2042799 PG 8 WC Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BA8VD UT WOS:000338775800159 ER PT S AU Kontson, K Jennings, RJ AF Kontson, Kimberly Jennings, Robert J. BE Whiting, BR Hoeschen, C Kontos, D TI X-ray scatter characterization in dedicated breast CT with bowtie filters SO MEDICAL IMAGING 2014: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging - Physics of Medical Imaging CY FEB 17-20, 2014 CL San Diego, CA SP Soc Photo Opt Instrumentat Engn, Modus Med Devices Inc, XIFIN Inc, Ventana Med Systems Inc, Intrace Med, Caresteam, GE Healthcare DE bowtie filter; breast CT; scatter-to-primary ratio ID MONTE-CARLO-SIMULATION; IMAGE QUALITY; RADIATION; DESIGN; CBCT AB The scatter contamination of projection images in cone-beam computed tomography (CT) degrades image quality. The use of bowtie filters in dedicated breast CT can decrease this scatter contribution. Three bowtie filter designs that compensate for one or more aspects of the beam-modifying effects due to the differences in path length in a projection have been studied. The first produces the same beam-hardening effect as breast tissue with a single-material design. The second produces the same beam quality and intensity at the detector with a two-material design and the third eliminates the beam-hardening effect by adjusting the bowtie filter thickness such that the same effective attenuation is produced at the detector. We have selected aluminum, boron carbide/beryllium oxide, and PM MA as the materials for the previously described designs, respectively. These designs have been investigated in terms of their ability to reduce the scatter contamination in projection images acquired in a dedicated breast CT geometry. The magnitude of the scatter was measured as the scatter-to-primary ratio using experimental and Monte Carlo techniques. The distribution of the scatter was also measured at different locations in the scatter image to produce scatter distribution maps for all three bowtie filter designs. The results of this study will be useful in designing scatter correction methods and understanding the benefits of bowtie filters in dedicated breast CT. C1 [Kontson, Kimberly; Jennings, Robert J.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Kontson, K (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. OI KONTSON, KIMBERLY/0000-0002-4978-6011 NR 14 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 978-0-8194-9826-7 J9 PROC SPIE PY 2014 VL 9033 AR 903343 DI 10.1117/12.2043051 PG 12 WC Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BA8VD UT WOS:000338775800141 ER PT J AU Shabalina, SA Ogurtsov, AY Spiridonov, NA Koonin, EV AF Shabalina, Svetlana A. Ogurtsov, Aleksey Y. Spiridonov, Nikolay A. Koonin, Eugene V. TI Evolution at protein ends: major contribution of alternative transcription initiation and termination to the transcriptome and proteome diversity in mammals SO NUCLEIC ACIDS RESEARCH LA English DT Article ID INTRINSICALLY DISORDERED REGIONS; EUKARYOTIC MESSENGER-RNAS; GENOME BROWSER DATABASE; SPLICE-SITE CHOICE; SELECTION PRESSURE; UNTRANSLATED REGIONS; FUNCTIONAL DIVERSITY; INTERACTION NETWORKS; SECONDARY STRUCTURE; INTERGENIC REGIONS AB Alternative splicing (AS), alternative transcription initiation (ATI) and alternative transcription termination (ATT) create the extraordinary complexity of transcriptomes and make key contributions to the structural and functional diversity of mammalian proteomes. Analysis of mammalian genomic and transcriptomic data shows that contrary to the traditional view, the joint contribution of ATI and ATT to the transcriptome and proteome diversity is quantitatively greater than the contribution of AS. Although the mean numbers of protein-coding constitutive and alternative nucleotides in gene loci are nearly identical, their distribution along the transcripts is highly non-uniform. On average, coding exons in the variable 5' and 3' transcript ends that are created by ATI and ATT contain approximately four times more alternative nucleotides than core protein-coding regions that diversify exclusively via AS. Short upstream exons that encompass alternative 5'-untranslated regions and N-termini of proteins evolve under strong nucleotide-level selection whereas in 3'-terminal exons that encode protein C-termini, protein-level selection is significantly stronger. The groups of genes that are subject to ATI and ATT show major differences in biological roles, expression and selection patterns. C1 [Shabalina, Svetlana A.; Ogurtsov, Aleksey Y.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20984 USA. [Spiridonov, Nikolay A.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20984 USA. EM shabalin@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.gov FU Department of Health and Human Services (DHHS) (National Institutes of Health, National Library of Medicine) FX Department of Health and Human Services (DHHS) (National Institutes of Health, National Library of Medicine) intramural funds. Funding for open access charge: DHHS (National Institutes of Health, National Library of Medicine) intramural funds. NR 78 TC 11 Z9 11 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2014 VL 42 IS 11 BP 7132 EP 7144 DI 10.1093/nar/gku342 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AK9TG UT WOS:000338769400035 PM 24792168 ER PT S AU Selen, A AF Selen, Arzu BE BarShalom, D Rose, K TI Pediatric Formulations and Dosage Forms and Future Opportunities: Impact of Regulations in the USA and Implementation of Quality by Design SO PEDIATRIC FORMULATIONS: A ROADMAP SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Article; Book Chapter ID SHRIVER NATIONAL INSTITUTE; CHILD HEALTH; THERAPEUTIC ORPHAN; MEDICATION ERRORS; ETHICAL CONDUCT; CLINICAL-TRIALS; EVALUATE DRUGS; INFORMATION; GUIDELINES; MEDICINES AB The advances in pharmaceutical sciences and technology have been so significant that Peter Drucker's quote that "the future has already happened" applies readily for medicines developed for adults. For pediatric patients, the future is about to happen. The continuation of focused partnerships and knowledge sharing and leveraging are critical to ensure that pediatric patients have timely access to high quality drug products that were developed with pediatric patients in mind. An overview of regulatory efforts, regulations and legislation to address the challenges for pediatric drug development are discussed. The implementation of regulatory incentives, the Pediatric Rule, Best Pharmaceuticals for Children Act, and Pediatric Research Equity Act, is having an impact and has led to incorporation of information for dosing of approximately 500 drug products since 1998 starting with implementation of the Pediatric Rule. There are significant accomplishments and a lot more work ahead for the pediatric community. The labeling information is usually for older pediatric patients and the need for information for safe and effective dosing of patients of 6 years old or younger remains. Some of the study outcomes are inconclusive with respect to safety and efficacy, and support the hypotheses that better understanding of drug delivery to pediatric patients is needed for determining and delivering the right dose to the pediatric patients. The 2012 Food and Drug Administration Safety and Innovation Act and implementation of Quality by Design paradigm focusing on drug product design and manufacturing process are expected to have a synergistic effect for continuing to advance development of pediatric dosage forms and formulations for the benefit of the pediatric patients. C1 US FDA, Off New Drug Qual Assessment, CDER, Silver Spring, MD 20993 USA. RP Selen, A (reprint author), US FDA, Off New Drug Qual Assessment, CDER, 10903 New Hampshire Ave,Bldg 21,Room 1604, Silver Spring, MD 20993 USA. EM Arzu.Selen@fda.hhs.gov NR 65 TC 0 Z9 0 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2210-7371 BN 978-1-4899-8011-3; 978-1-4899-8010-6 J9 AAPS ADV PHARM SCI PY 2014 VL 11 BP 377 EP 393 DI 10.1007/978-1-4899-8011-3_26 D2 10.1007/978-1-4899-8011-3 PG 17 WC Pediatrics; Pharmacology & Pharmacy SC Pediatrics; Pharmacology & Pharmacy GA BA6BB UT WOS:000337084700027 ER PT B AU Seeff, LB Ghany, MG AF Seeff, Leonard B. Ghany, Marc G. BE Thompson, G TI HARVEY ALTER AND MICHAEL HOUGHTON: THE DISCOVERY OF HEPATITIS C AND THE INTRODUCTION OF SCREENING TO PREVENT ITS TRANSMISSION IN TRANSFUSED BLOOD SO PIONEERS OF MEDICINE WITHOUT A NOBEL PRIZE LA English DT Article; Book Chapter ID NON-B-HEPATITIS; NON-A-HEPATITIS; UNITED-STATES; POSTTRANSFUSION HEPATITIS; AUSTRALIA ANTIGEN; NATURAL-HISTORY; VIRUS; JAUNDICE; SEQUENCE; ANTIBODY C1 [Seeff, Leonard B.] Hill Grp, Bethesda, MD 20817 USA. [Seeff, Leonard B.] US FDA, Silver Spring, MD USA. [Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. RP Seeff, LB (reprint author), Hill Grp, Bethesda, MD 20817 USA. NR 39 TC 0 Z9 0 U1 1 U2 2 PU IMPERIAL COLL PRESS PI COVENT GARDEN PA 57 SHELTON STREET, COVENT GARDEN WC2H 9HE, ENGLAND BN 978-1-78326-384-4; 978-1-78326-385-1; 978-1-78326-383-7 PY 2014 BP 197 EP 214 D2 10.1142/p922 PG 18 WC History & Philosophy Of Science SC History & Philosophy of Science GA BA6ZY UT WOS:000337341800014 ER PT J AU Chien, CY Chang, CW Tsai, CA Chen, JJ AF Chien, Chih-Yi Chang, Ching-Wei Tsai, Chen-An Chen, James J. TI MAVTgsa: An R Package for Gene Set (Enrichment) Analysis SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID MULTIPLE END-POINTS; EXPRESSION DATA; GLOBAL TEST; CANCER; KNOWLEDGE; PATHWAYS AB Gene set analysis methods aim to determine whether an a priori defined set of genes shows statistically significant difference in expression on either categorical or continuous outcomes. Although many methods for gene set analysis have been proposed, a systematic analysis tool for identification of different types of gene set significance modules has not been developed previously. This work presents an R package, called MAVTgsa, which includes three different methods for integrated gene set enrichment analysis. (1) The one-sided OLS (ordinary least squares) test detects coordinated changes of genes in gene set in one direction, either up- or downregulation. (2) The two-sided MANOVA (multivariate analysis variance) detects changes both up-and downregulation for studying two or more experimental conditions. (3) A random forests-based procedure is to identify gene sets that can accurately predict samples from different experimental conditions or are associated with the continuous phenotypes. MAVTgsa computes the.. values and FDR (false discovery rate) q-value for all gene sets in the study. Furthermore, MAVTgsa provides several visualization outputs to support and interpret the enrichment results. This package is available online. C1 [Chien, Chih-Yi] Keelung Chang Gung Mem Hosp, Community Med Res Ctr, Keelung 204, Taiwan. [Chang, Ching-Wei; Chen, James J.] Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. [Tsai, Chen-An] Natl Taiwan Univ, Dept Agron, Taipei 106, Taiwan. [Chen, James J.] China Med Univ, Grad Inst Biostat, Taichung, Taiwan. [Chen, James J.] China Med Univ, Ctr Biostat, Taichung, Taiwan. RP Tsai, CA (reprint author), Natl Taiwan Univ, Dept Agron, 1,Sect 4,Roosevelt Rd, Taipei 106, Taiwan. EM catsai@ntu.edu.tw; jamesj.chen@fda.hhs.gov OI Tsai, Chen-An/0000-0002-7490-4331 FU Post-doctoral Fellowship Program at the NCTR FX Chih-Yi's research was supported by the Post-doctoral Fellowship Program at the NCTR administered by the Oak Ridge Institute for Science and Education through an interagency agreement between USDOE and USFDA. NR 31 TC 1 Z9 1 U1 1 U2 4 PU HINDAWI PUBLISHING CORPORATION 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 2014 AR 346074 DI 10.1155/2014/346074 PG 11 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AL1BJ UT WOS:000338860500001 ER PT J AU Chalbot, MCG Brown, J Chitranshi, P da Costa, GG Pollock, ED Kavouras, IG AF Chalbot, M. -C. G. Brown, J. Chitranshi, P. da Costa, G. Gamboa Pollock, E. D. Kavouras, I. G. TI Functional characterization of the water-soluble organic carbon of size-fractionated aerosol in the southern Mississippi Valley SO ATMOSPHERIC CHEMISTRY AND PHYSICS LA English DT Article ID MAGNETIC-RESONANCE-SPECTROSCOPY; BIOMASS BURNING AEROSOLS; LOS-ANGELES BASIN; PARTICULATE MATTER; ATMOSPHERIC AEROSOLS; DICARBOXYLIC-ACIDS; ISOTOPIC COMPOSITIONS; SOURCE APPORTIONMENT; SEASONAL-VARIATION; ALIPHATIC-AMINES AB The chemical content of water-soluble organic carbon (WSOC) as a function of particle size was characterized in Little Rock, Arkansas in winter and spring 2013. The objectives of this study were to (i) compare the functional characteristics of coarse, fine and ultrafine WSOC and (ii) reconcile the sources of WSOC for periods when carbonaceous aerosol was the most abundant particulate component. The WSOC accounted for 5% of particle mass for particles with d(p) > 0.96 mu m and 10% of particle mass for particles with d(p) < 0.96 mu m. Non-exchangeable aliphatic (H-C), unsaturated aliphatic (H-C-C=), oxygenated saturated aliphatic (H-C-O), acetalic (O-CH-O) and aromatic (Ar-H) protons were determined by proton nuclear magnetic resonance (H-1-NMR). The total non-exchangeable organic hydrogen concentrations varied from 4.1 +/- 0.1 nmol m(-3) for particles with 1.5 < d(p) < 3.0 mu m to 73.9 +/- 12.3 nmol m(-3) for particles with d(p) < 0.49 mu m. The molar H / C ratios varied from 0.48 +/- 0.05 to 0.92 +/- 0.09, which were comparable to those observed for combustion-related organic aerosol. The R-H was the most abundant group, representing about 45% of measured total non-exchangeable organic hydrogen concentrations, followed by H-C-O (27%) and H-C-C= (26%). Levoglucosan, amines, ammonium and methanesulfonate were identified in NMR fingerprints of fine particles. Sucrose, fructose, glucose, formate and acetate were associated with coarse particles. These qualitative differences of H-1-NMR profiles for different particle sizes indicated the possible contribution of biological aerosols and a mixture of aliphatic and oxygenated compounds from biomass burning and traffic exhausts. The concurrent presence of ammonium and amines also suggested the presence of ammonium/aminium nitrate and sulfate secondary aerosol. The size-dependent origin of WSOC was further corroborated by the increasing delta C-13 abundance from -26.81 +/- 0.18 parts per thousand for the smallest particles to -25.93 +/- 0.31 parts per thousand for the largest particles and the relative distribution of the functional groups as compared to those previously observed for marine, biomass burning and secondary organic aerosol. The latter also allowed for the differentiation of urban combustion-related aerosol and biological particles. The five types of organic hydrogen accounted for the majority of WSOC for particles with d(p) > 3.0 mu m and d(p) < 0.96 mu m. C1 [Chalbot, M. -C. G.; Brown, J.; Kavouras, I. G.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Chitranshi, P.; da Costa, G. Gamboa] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Pollock, E. D.] Univ Arkansas, Stable Isotope Lab, Fayetteville, AR 72701 USA. RP Kavouras, IG (reprint author), Univ Arkansas Med Sci, Little Rock, AR 72205 USA. EM ikavouras@uams.edu RI Kavouras, Ilias/H-7056-2012 OI pollock, erik/0000-0002-2834-4935; Kavouras, Ilias/0000-0003-0342-5306; Kavouras, Ilias/0000-0003-0436-3784 FU Intramural FDA HHS [FD999999] NR 75 TC 11 Z9 11 U1 1 U2 36 PU COPERNICUS GESELLSCHAFT MBH PI GOTTINGEN PA BAHNHOFSALLEE 1E, GOTTINGEN, 37081, GERMANY SN 1680-7316 EI 1680-7324 J9 ATMOS CHEM PHYS JI Atmos. Chem. Phys. PY 2014 VL 14 IS 12 BP 6075 EP 6088 DI 10.5194/acp-14-6075-2014 PG 14 WC Meteorology & Atmospheric Sciences SC Meteorology & Atmospheric Sciences GA AK5BH UT WOS:000338438300014 PM 27471518 ER PT J AU Tworkoski, E Dorris, E Shin, D Phillips, KS AF Tworkoski, Ellen Dorris, Eric Shin, Daniel Phillips, K. Scott TI A high-throughput method for testing biofouling and cleaning of polymer hydrogel materials used in medical devices SO ANALYTICAL METHODS LA English DT Article ID CONTACT-LENSES; SURFACES; PROTEIN; CONTAMINATION; FLUORESCENCE; INSTRUMENTS; RESPONSES; ADHESION; RELEASE AB A miniaturized, high-throughput method is developed to measure biofouling and cleaning processes of transparent silicone-and hydroxyethylmethacrylate-based polymer hydrogel materials used in medical devices. Protein biofouling and cleaning effectiveness were measured in 384-well microtiter plates using 3 mm biopsy punches from hydrogel materials soaked in a simulated protein soil fluid (PSF). Fluorescence detection of labeled protein components enabled highly sensitive quantification of biofouling and cleaning endpoints. The sample volume to soaking volume ratio and surface area to soaking volume ratio are similar to those used for full-sized analysis. The method showed minimal perturbation from sample height variations up to hundreds of micrometers. A calibration curve constructed by testing samples soaked in eight different concentrations (0-1.25 mg mL(-1)) of fluorescent protein showed a broad dynamic range, but fluorescence quenching occurred above 0.75 mg mL(-1) protein in highly absorbing hydrogels. The method was found to have 1 : 1 linear correlation with measurements obtained by 2D fluorescence imaging using biofouled/ cleaned miniature punches, and 3D confocal fluorescence profiling using full-sized samples soaked in PSF. A comparison of protein biofouling on two types of hydrogel materials revealed that the slope of protein concentration-response curves for high water materials was 100-fold higher than for low water materials. To demonstrate simultaneous measurement of biofouling by multiple soil components, lipid and protein sorption were also tested and found to be correlated. The characterization and results obtained here show the potential of this method for exploring mechanistic details of biofouling and cleaning processes. The method greatly decreases the time and cost associated with the large number of unique samples required, making it possible to study the roles of the numerous material, solution and soil variables at the biointerface of medical devices. C1 [Tworkoski, Ellen; Dorris, Eric; Shin, Daniel; Phillips, K. Scott] US FDA, Off Med Prod & Tobacco, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs,Div Chem & Mat Sci, Silver Spring, MD 20993 USA. RP Phillips, KS (reprint author), US FDA, Off Med Prod & Tobacco, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs,Div Chem & Mat Sci, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM kenneth.phillips@fda.hhs.gov RI Phillips, Kenneth/A-2156-2013; phillips, kenneth/F-7560-2014 OI Phillips, Kenneth/0000-0002-6552-0694; phillips, kenneth/0000-0002-6552-0694 NR 38 TC 4 Z9 4 U1 2 U2 13 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 2014 VL 6 IS 13 BP 4521 EP 4529 DI 10.1039/c3ay40501j PG 9 WC Chemistry, Analytical; Food Science & Technology; Spectroscopy SC Chemistry; Food Science & Technology; Spectroscopy GA AJ5XI UT WOS:000337763200008 ER PT J AU Zhai, XZ Jia, HM Zhang, YE Lei, Y Wei, J Gao, YH Chu, JH He, WW Yin, JJ Zheng, Z AF Zhai, Xuezhen Jia, Huimin Zhang, Yange Lei, Yan Wei, Jie Gao, Yuanhao Chu, Junhao He, Weiwei Yin, Jun-Jie Zheng, Zhi TI In situ fabrication of Cu2ZnSnS4 nanoflake thin films on both rigid and flexible substrates SO CRYSTENGCOMM LA English DT Article ID SOLAR-CELLS; NANOCRYSTALS; GROWTH; PRECURSORS; EFFICIENCY AB Cu2ZnSnS4 (CZTS) thin film, a highly promising and low-cost absorber layer material for solar cells, has been in situ fabricated on stainless steel and FTO glass substrates for the first time, using a one-step solvothermal treatment of CuZnSn-alloyed film with sulphur or selenium powder. The resulting products were characterized by X-ray diffractometry (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and UV-vis-NIR spectroscopy. Raman spectroscopy was used to characterize and confirm the formation of CZTS. The effects of temperature, reaction time, the ratio of Cu/Zn/Sn, and non-elemental reactants on the formation of CZTS nanocrystal films were assessed, and we found that the reaction temperature was a key factor in determining the properties of the final products. Pure CZTS phase forms at a temperature of 250 degrees C or higher. Our method produces CZTS thin films at 250 degrees C, the lowest reaction temperature that can be used in the process and the lowest temperature of any current fabrication system. We also found that flexible substrates promote the growth of CZTS nanocrystals. Using flexible substrates in the in situ fabrication of nanocrystalline thin films may make it possible to use CZTS for industrial applications. C1 [Zhai, Xuezhen; Jia, Huimin; Zhang, Yange; Lei, Yan; Wei, Jie; Gao, Yuanhao; He, Weiwei; Zheng, Zhi] Xuchang Univ, Inst Surface Micro & Nano Mat, Key Lab Micronano Energy Storage & Convers Mat He, Xuchang 461000, Henan, Peoples R China. [Zhai, Xuezhen; Wei, Jie; Chu, Junhao] E China Normal Univ, Dept Elect, Minist Educ, Key Lab Polar Mat & Devices, Shanghai 200241, Peoples R China. [He, Weiwei; Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Zhai, XZ (reprint author), Xuchang Univ, Inst Surface Micro & Nano Mat, Key Lab Micronano Energy Storage & Convers Mat He, Xuchang 461000, Henan, Peoples R China. EM zhengzhi99999@gmail.com RI Yin, Jun Jie /E-5619-2014 FU National Natural Science Foundation of China [21273192, 61204009]; Innovation Scientists and Technicians Troop Construction Projects of Henan Province [144200510014]; Program for Science & Technology Innovation Teams in the Universities of Henan Province [2012 IRTSTHN021]; Innovation Scientists and Technicians Team Projects of Henan Province Program for Basic and Advanced Technology of Henan Province [112300410106, 124300510055]; Science and Technology of Henan Province [12A150022] FX We thank Barbara Berman from U.S. FDA for her kind and scientific editing. This work was supported by the National Natural Science Foundation of China (grant no. 21273192, 61204009), the Innovation Scientists and Technicians Troop Construction Projects of Henan Province (grant no. 144200510014), the Program for Science & Technology Innovation Teams in the Universities of Henan Province (2012 IRTSTHN021), the Innovation Scientists and Technicians Team Projects of Henan Province Program for Basic and Advanced Technology of Henan Province (grant no. 112300410106, 124300510055), and the Research Key Projects of Science and Technology of Henan Province (grant no. 12A150022). NR 27 TC 12 Z9 12 U1 9 U2 50 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1466-8033 J9 CRYSTENGCOMM JI Crystengcomm PY 2014 VL 16 IS 27 BP 6244 EP 6249 DI 10.1039/c4ce00174e PG 6 WC Chemistry, Multidisciplinary; Crystallography SC Chemistry; Crystallography GA AJ9MV UT WOS:000338036400034 ER PT J AU Weisz, A Krantz, ZB AF Weisz, Adrian Krantz, Zoe B. TI Determination of synthetic by-products and an intermediate in the colour additives D&C Red Nos 27 and 28 (phloxine B) and their lakes using conventional HPLC SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT LA English DT Article DE D&C Red No. 27; D&C Red No. 28; phloxine B; 2,3,4,5-tetrachloro-6-(3 ',5 '-dibromo-2 ',4 '-dihydroxybenzoyl) benzoic acid; brominated resorcinols; 3,4,5,6-tetrachlorophthalic acid; HPLC ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ETHERS AB Specifications in the US Code of Federal Regulations (CFR) for the colour additives D&C Red No. 27 (R27) and D&C Red No. 28 (R28) limit the levels of the synthetic by-products 2,3,4,5-tetrachloro-6-(3',5'-dibromo-2',4'-dihydroxybenzoyl) benzoic acid (SBBA) and "brominated resorcinol" and of the intermediate 3,4,5,6-tetrachlorophthalic acid (TCPA). The present study reports the development and application of a conventional HPLC method for the quantitative determination of these impurities in R27, R28 and their lakes. Because the CFR-listed "brominated resorcinol" refers to a group of synthetic by-products, six variously brominated resorcinols were examined as possible impurities. Due to their rapid decomposition in the presence of the dye, the existence of any brominated resorcinols in R27 and R28 is highly unlikely, and this supposition is supported by the results obtained in this study. SBBA, 2,4,6-tribromoresorcinol (Br3R, the brominated resorcinol most likely to be found as an impurity) and TCPA were quantified by using five-point calibration curves with data points (w/w) that ranged from 0.066% to 0.820% for SBBA, from 0.050% to 0.499% for Br3R, and from 0.061% to 1.410% for TCPA. The HPLC method was applied to the analysis of test portions from batches of R27, R28 and their lakes submitted to the USFDA for certification by domestic and foreign manufacturers. C1 [Weisz, Adrian; Krantz, Zoe B.] US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20740 USA. RP Weisz, A (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20740 USA. EM adrian.weisz@fda.hhs.gov NR 14 TC 1 Z9 1 U1 2 U2 3 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 2014 VL 31 IS 6 BP 979 EP 984 DI 10.1080/19440049.2014.905714 PG 6 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA AJ9IT UT WOS:000338023300002 PM 24646430 ER PT S 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 BE Aylward, S Hadjiiski, LM TI Seamless Insertion of Real Pulmonary Nodules in Chest CT Exams SO MEDICAL IMAGING 2014: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 18-20, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN, Inc, Ventana Med Syst Inc, Intrace Med DE Reference library creation; Lesion insertion; Chest CT; Poisson image editing ID COMPUTER-AIDED DIAGNOSIS; FINITE-SAMPLE SIZE; LUNG NODULES; SIMULATION; PERFORMANCE; LESIONS AB The availability of large medical image datasets is critical in many applications such as training and testing of computer aided diagnosis (CAD) systems, evaluation of segmentation algorithms, and conducting perceptual studies. However, collection of large repositories of clinical images is hindered by the high cost and difficulties associated with both the accumulation of data and establishment of the ground truth. To address this problem, we are developing an image blending tool that allows users to modify or supplement existing datasets by seamlessly inserting a real lesion extracted from a source image into a different location on 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 blended image by limiting user involvement to two simple steps: the user first draws a casual boundary around the nodule of interest in the source, and then selects the center of desired insertion area in the target. We demonstrate examples of the performance of the proposed system on samples taken from the Lung Image Database Consortium (LIDC) dataset, and compare the noise power spectrum (NPS) of blended nodules versus that of native nodules in simulated phantoms. C1 [Pezeshk, Aria; Sahiner, Berkman; Zeng, Rongping; Wunderlich, Adam; Chen, Weijie; Petrick, Nicholas] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Pezeshk, A (reprint author), WO62-4110,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM aria.pezeshk@fda.hhs.gov NR 21 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 978-0-8194-9828-1 J9 PROC SPIE PY 2014 VL 9035 AR 90351K DI 10.1117/12.2043786 PG 10 WC Engineering, Electrical & Electronic; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA7XB UT WOS:000337842400052 ER PT J AU Nagarkatti, R de Araujo, FF Gupta, C Debrabant, A AF Nagarkatti, Rana de Araujo, Fernanda Fortes Gupta, Charu Debrabant, Alain TI Aptamer Based, Non-PCR, Non-Serological Detection of Chagas Disease Biomarkers in Trypanosoma cruzi Infected Mice SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID EXCRETED-SECRETED ANTIGENS; DISCOVERY; SERUM; ANTIBODIES; IDENTIFICATION; SERODIAGNOSIS; DIAGNOSIS; SELECTION; EFFICACY; TOOLS AB Chagas disease affects about 5 million people across the world. The etiological agent, the intracellular parasite Trypanosoma cruzi (T. cruzi), can be diagnosed using microscopy, serology or PCR based assays. However, each of these methods has their limitations regarding sensitivity and specificity, and thus to complement these existing diagnostic methods, alternate assays need to be developed. It is well documented that several parasite proteins called T. cruzi Excreted Secreted Antigens (TESA), are released into the blood of an infected host. These circulating parasite antigens could thus be used as highly specific biomarkers of T. cruzi infection. In this study, we have demonstrated that, using a SELEx based approach, parasite specific ligands called aptamers, can be used to detect TESA in the plasma of T. cruzi infected mice. An Enzyme Linked Aptamer (ELA) assay, similar to ELISA, was developed using biotinylated aptamers to demonstrate that these RNA ligands could interact with parasite targets. Aptamer L44 (Apt-L44) showed significant and specific binding to TESA as well as T. cruzi trypomastigote extract and not to host proteins or proteins of Leishmania donovani, a related trypanosomatid parasite. Our result also demonstrated that the target of Apt-L44 is conserved in three different strains of T. cruzi. In mice infected with T. cruzi, Apt-L44 demonstrated a significantly higher level of binding compared to non-infected mice suggesting that it could detect a biomarker of T. cruzi infection. Additionally, Apt-L44 could detect these circulating biomarkers in both the acute phase, from 7 to 28 days post infection, and in the chronic phase, from 55 to 230 days post infection. Our results show that Apt-L44 could thus be used in a qualitative ELA assay to detect biomarkers of Chagas disease. C1 [Nagarkatti, Rana; de Araujo, Fernanda Fortes; Gupta, Charu; Debrabant, Alain] US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Nagarkatti, R (reprint author), US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM alain.debrabant@fda.hhs.gov OI Gupta, Charu/0000-0002-7437-6559 FU Food and Drug Administration FX The funding for this study was obtained via intramural grants from the Food and Drug Administration. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 8 Z9 8 U1 0 U2 15 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 2014 VL 8 IS 1 AR e2650 DI 10.1371/journal.pntd.0002650 PG 10 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AJ8SI UT WOS:000337977300043 PM 24454974 ER PT J AU Bai, JPF Fontana, RJ Price, ND Sangar, V AF Bai, Jane P. F. Fontana, Robert J. Price, Nathan D. Sangar, Vineet TI Systems pharmacology modeling: an approach to improving drug safety SO BIOPHARMACEUTICS & DRUG DISPOSITION LA English DT Review DE systems biology; molecular pathways; molecular networks; mitochondria; gene drug interaction; biomarkers; clinical phenotype; organ injury; cellular phenotype ID MITOCHONDRIAL PROTEIN-SYNTHESIS; HIV-INFECTED PATIENTS; FATTY-ACID OXIDATION; INDUCED LIVER-INJURY; GROWTH-FACTOR-BETA; SKELETAL-MUSCLE; VALPROIC ACID; GLOBAL RECONSTRUCTION; HEPATIC STEATOSIS; LACTIC-ACIDOSIS AB Advances in systems biology in conjunction with the expansion in knowledge of drug effects and diseases present an unprecedented opportunity to extend traditional pharmacokinetic and pharmacodynamic modeling/analysis to conduct systems pharmacology modeling. Many drugs that cause liver injury and myopathies have been studied extensively. Mitochondrion-centric systems pharmacology modeling is important since drug toxicity across a large number of pharmacological classes converges to mitochondrial injury and death. Approaches to systems pharmacology modeling of drug effects need to consider drug exposure, organelle and cellular phenotypes across all key cell types of human organs, organ-specific clinical biomarkers/phenotypes, gene-drug interaction and immune responses. Systems modeling approaches, that leverage the knowledge base constructed from curating a selected list of drugs across a wide range of pharmacological classes, will provide a critically needed blueprint for making informed decisions to reduce the rate of attrition for drugs in development and increase the number of drugs with an acceptable benefit/risk ratio. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Bai, Jane P. F.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Fontana, Robert J.] Univ Michigan, Dept Internal Med, Sch Med, Ann Arbor, MI 48109 USA. [Price, Nathan D.; Sangar, Vineet] Inst Syst Biol, Seattle, WA 98109 USA. 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 NR 80 TC 9 Z9 9 U1 2 U2 11 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 JAN PY 2014 VL 35 IS 1 SI SI BP 1 EP 14 DI 10.1002/bdd.1871 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AJ2WR UT WOS:000337525700001 PM 24136298 ER PT J AU Kempic, A AF Kempic, Annamarie TI Inaugural Eric M. Blumberg Memorial Lecture SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 [Kempic, Annamarie] US FDA, Rockville, MD 20857 USA. RP Kempic, A (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2014 VL 69 IS 2 BP 137 EP 142 PG 6 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA AJ2NX UT WOS:000337495700001 PM 25163208 ER PT J AU Ning, BT Su, ZQ Mei, N Hong, HX Deng, HL Shi, LM Fuscoe, JC Tolleson, WH AF Ning, Baitang Su, Zhenqiang Mei, Nan Hong, Huixiao Deng, Helen Shi, Leming Fuscoe, James C. Tolleson, William H. TI Toxicogenomics and Cancer Susceptibility: Advances with Next-Generation Sequencing SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE Cancer; carcinogenesis; genomics; toxicogenomics; environmental exposure; next generation sequencing ID METASTATIC COLORECTAL-CANCER; CELL LUNG-CANCER; METHYLENETETRAHYDROFOLATE REDUCTASE POLYMORPHISM; FAMILIAL ADENOMATOUS POLYPOSIS; GENE-ENVIRONMENT INTERACTIONS; AFFECT DNA METHYLATION; ACUTE MYELOID-LEUKEMIA; NIS-TRANSFORMED CELLS; BREAST-CANCER; HUMAN TRANSCRIPTOME AB The aim of this review is to comprehensively summarize the recent achievements in the field of toxicogenomics and cancer research regarding genetic-environmental interactions in carcinogenesis and detection of genetic aberrations in cancer genomes by next-generation sequencing technology. Cancer is primarily a genetic disease in which genetic factors and environmental stimuli interact to cause genetic and epigenetic aberrations in human cells. Mutations in the germline act as either high-penetrance alleles that strongly increase the risk of cancer development, or as low-penetrance alleles that mildly change an individual's susceptibility to cancer. Somatic mutations, resulting from either DNA damage induced by exposure to environmental mutagens or from spontaneous errors in DNA replication or repair are involved in the development or progression of the cancer. Induced or spontaneous changes in the epigenome may also drive carcinogenesis. Advances in next-generation sequencing technology provide us opportunities to accurately, economically, and rapidly identify genetic variants, somatic mutations, gene expression profiles, and epigenetic alterations with single-base resolution. Whole genome sequencing, whole exome sequencing, and RNA sequencing of paired cancer and adjacent normal tissue present a comprehensive picture of the cancer genome. These new findings should benefit public health by providing insights in understanding cancer biology, and in improving cancer diagnosis and therapy. C1 [Ning, Baitang; Su, Zhenqiang; Mei, Nan; Hong, Huixiao; Shi, Leming; Fuscoe, James C.; Tolleson, William H.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Deng, Helen] Arkansas Dept Hlth & Human Serv, Little Rock, AR USA. [Shi, Leming] Fudan Univ, Sch Pharm, Ctr Pharmacogen, Shanghai 200433, Peoples R China. RP Ning, BT (reprint author), Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT100, Jefferson, AR 72079 USA. EM baitang.ning@fda.hhs.gov RI mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 NR 224 TC 8 Z9 11 U1 2 U2 27 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 2014 VL 32 IS 2 BP 121 EP 158 DI 10.1080/10590501.2014.907460 PG 38 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA AJ4AB UT WOS:000337610000002 PM 24875441 ER PT J AU He, WW Wamer, W Xia, QS Yin, JJ Fu, PP AF He, Weiwei Wamer, Wayne Xia, Qingsu Yin, Jun-jie Fu, Peter P. TI Enzyme-Like Activity of Nanomaterials SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE Nanomaterial; peroxidase-like activity; oxidase-like activity; catalase-like activity; superoxide dismutase-like activity; electron spin resonance ID PEROXIDASE-LIKE ACTIVITY; STABILIZED AU NANOCLUSTERS; IRON-OXIDE NANOPARTICLES; CATALYTIC-ACTIVITY; HYDROGEN-PEROXIDE; COLORIMETRIC DETECTION; GOLD NANOPARTICLES; LIPID-PEROXIDATION; GLUCOSE DETECTION; PLATINUM NANOPARTICLES AB Due to possessing an extremely small size and a large surface area per unit of volume, nanomaterials have specific characteristic physical, chemical, photochemical, and biological properties that are very useful in many new applications. Nanoparticles' catalytic activity and intrinsic ability in generating or scavenging reactive oxygen species in general can be used to mimic the catalytic activity of natural enzymes. Many nanoparticles with enzyme-like activities have been found, potentially capable of being applied for commercial uses, such as in biosensors, pharmaceutical processes, and the food industry. To date, a variety of nanoparticles, especially those formed from noble metals, have been determined to possess oxidase-like, peroxidase-like, catalase-like, and/or superoxide dismutase-like activity. The ability of nanoparticles to mimic enzymatic activity, especially peroxidase mimics, can be used in a variety of applications, such as detection of glucose in biological samples and waste water treatment. To study the enzyme-like activity of nanoparticles, the electron spin resonance method represents a critically important and convenient analytical approach for zero-time detection of the reactive substrates and products as well as for mechanism determination. C1 [He, Weiwei] Xuchang Univ, Inst Surface Micro & Nano Mat, Key Lab Micronano Mat Energy Storage & Convers He, Xuchang, Henan, Peoples R China. [He, Weiwei; Wamer, Wayne; Yin, Jun-jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Xia, Qingsu; Fu, Peter P.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Yin, JJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM junjie.yin@fda.hhs.gov RI Yin, Jun Jie /E-5619-2014 FU National Natural Science Foundation of China [201303153] FX W. He thanks the National Natural Science Foundation of China (Grant No. 201303153) for support. NR 99 TC 17 Z9 17 U1 20 U2 114 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 2014 VL 32 IS 2 BP 186 EP 211 DI 10.1080/10590501.2014.907462 PG 26 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA AJ4AB UT WOS:000337610000004 PM 24875443 ER PT J AU Dankmeyer, JL Fast, RL Cote, CK Worsham, PL Fritz, D Fisher, D Kern, SJ Merkel, T Kirschning, CJ Amemiya, K AF Dankmeyer, Jennifer L. Fast, Randy L. Cote, Christopher K. Worsham, Patricia L. Fritz, David Fisher, Diana Kern, Steven J. Merkel, Tod Kirschning, Carsten J. Amemiya, Kei TI Multiple Roles of Myd88 in the Immune Response to the Plague F1-V Vaccine and in Protection against an Aerosol Challenge of Yersinia pestis CO92 in Mice SO JOURNAL OF IMMUNOLOGY RESEARCH LA English DT Article ID FUSION PROTEIN VACCINE; RECOMBINANT V-ANTIGEN; TOLL-LIKE RECEPTOR-2; PNEUMONIC PLAGUE; LEGIONELLA-PNEUMOPHILA; NALP3 INFLAMMASOME; CUTTING EDGE; MONOCLONAL-ANTIBODIES; PHAGOSOME MATURATION; ACTIVE IMMUNIZATION AB The current candidate vaccine against Yersinia pestis infection consists of two subunit proteins: the capsule protein or F1 protein and the low calcium response V protein or V-antigen. Little is known of the recognition of the vaccine by the host's innate immune system and how it affects the acquired immune response to the vaccine. Thus, we vaccinated Toll-like receptor (Tlr) 2, 4, and 2/4-double deficient, as well as signal adaptor protein Myd88-deficient mice. We found that Tlr4 and Myd88 appeared to be required for an optimal immune response to the F1-V vaccine but not Tlr2 when compared to wild-type mice. However, there was a difference between the requirement for Tlr4 and MyD88 in vaccinated animals. When F1-V vaccinated Tlr4 mutant (lipopolysaccharide tolerant) and Myd88-deficient mice were challenged by aerosol with Y. pestis CO92, all but one Tlr4 mutant mice survived the challenge, but no vaccinated Myd88-deficient mice survived the challenge. Spleens from these latter nonsurviving mice showed that Y. pestis was not cleared from the infected mice. Our results suggest that MyD88 appears to be important for both an optimal immune response to F1-V and in protection against a lethal challenge of Y. pestis CO92 in F1-V vaccinated mice. C1 [Dankmeyer, Jennifer L.; Fast, Randy L.; Cote, Christopher K.; Worsham, Patricia L.; Fritz, David; Fisher, Diana; Kern, Steven J.; Amemiya, Kei] US Army, Med Res Inst Infect Dis, Frederick, MD 21703 USA. [Merkel, Tod] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Kirschning, Carsten J.] Univ Duisburg Essen, Inst Med Microbiol, Essen, Germany. RP Amemiya, K (reprint author), US Army, Med Res Inst Infect Dis, Frederick, MD 21703 USA. EM kei.amemiya@us.army.mil FU Joint Science and TechnologyOffice/Defense Threat Reduction Agency [1.1A0018 07_RD_B] FX The authors thank Steven Tobery and Anthony Bassett for their excellent technical assistance throughout this study. The authors thank Sarah Cohen for technical assistance in photomicroscopy. We also thank Stephen Little for critical reading of this paper. The authors thank the Joint Science and TechnologyOffice/Defense Threat Reduction Agency for support for this research (Project no. 1.1A0018 07_RD_B). Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army. NR 61 TC 0 Z9 0 U1 0 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-8861 EI 2314-7156 J9 J IMMUNOL RES JI J Immunol. Res. PY 2014 AR 341820 DI 10.1155/2014/341820 PG 13 WC Immunology SC Immunology GA AJ1SS UT WOS:000337436600001 ER PT S AU Gallas, BD Cheng, WC Gavrielides, MA Ivansky, A Keay, T Wunderlich, A Hipp, J Hewitt, SM AF Gallas, Brandon D. Cheng, Wei-Chung Gavrielides, Marios A. Ivansky, Adam Keay, Tyler Wunderlich, Adam Hipp, Jason Hewitt, Stephen M. BE MelloThoms, CR Kupinski, MA TI eeDAP: An Evaluation Environment for Digital and Analog Pathology SO MEDICAL IMAGING 2014: 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 FEB 16-17, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN Inc, Ventana Med Syst Inc, Intrace Med DE Digital Pathology; Whole Slide Imaging; Reader Studies; Technology Evaluation AB Purpose: The purpose of this work is to present a platform for designing and executing studies that compare pathologists interpreting histopathology of whole slide images (WSI) on a computer display to pathologists interpreting glass slides on an optical microscope. Methods: Here we present eeDAP, an evaluation environment for digital and analog pathology. The key element in eeDAP is the registration of the WSI to the glass slide. Registration is accomplished through computer control of the microscope stage and a camera mounted on the microscope that acquires images of the real time microscope view. Registration allows for the evaluation of the same regions of interest (ROIs) in both domains. This can reduce or eliminate disagreements that arise from pathologists interpreting different areas and focuses the comparison on image quality. Results: We reduced the pathologist interpretation area from an entire glass slide (approximate to 10-30 mm)(2) to small ROIs < (50 um)(2). We also made possible the evaluation of individual cells. Conclusions: We summarize eeDAP's software and hardware and provide calculations and corresponding images of the microscope field of view and the ROIs extracted from the WSIs. These calculations help provide a sense of eeDAP's functionality and operating principles, while the images provide a sense of the look and feel of studies that can be conducted in the digital and analog domains. The eeDAP software can be downloaded from code. google.com (project: eeDAP) as Matlab source or as a precompiled stand-alone license-free application. C1 [Gallas, Brandon D.; Cheng, Wei-Chung; Gavrielides, Marios A.; Ivansky, Adam; Keay, Tyler; Wunderlich, Adam] US FDA, Div Imaging & Appl Math, OSEL, CDRH, Silver Spring, MD 20993 USA. [Hipp, Jason; Hewitt, Stephen M.] Natl Inst Hlth, Natl Canc Inst, Ctr Canc Res, Pathol Lab, Bethesda, MD USA. RP Gallas, BD (reprint author), US FDA, Div Imaging & Appl Math, OSEL, CDRH, Silver Spring, MD 20993 USA. EM brandon.gallas@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620; Hewitt, Stephen/0000-0001-8283-1788 FU U. S. Food and Drug Administration (FDA/ CDRH) FX This research project was partially funded through a Critical Path grant from the U. S. Food and Drug Administration (FDA/ CDRH). We would like to acknowledge Catherine Conway, formerly at the NIH, for her active involvement in the project, including the preparation and annotation of slides and training materials.; . NR 9 TC 0 Z9 0 U1 0 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 978-0-8194-9830-4 J9 PROC SPIE PY 2014 VL 9037 AR UNSP 903709 DI 10.1117/12.2044443 PG 12 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA7IZ UT WOS:000337585600008 ER PT S AU He, X Samuelson, F Zeng, RP Sahiner, B AF He, Xin Samuelson, Frank Zeng, Rongping Sahiner, Berkman BE MelloThoms, CR Kupinski, MA TI Discover Common Properties of Human Observers' Visual Search and Mathematical Observers' Scanning PART I. Theory and Conjecture SO MEDICAL IMAGING 2014: 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 FEB 16-17, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN Inc, Ventana Med Syst Inc, Intrace Med DE visual search; effective set size; ROC curve; search performance; power-law-shaped ROC curve; uncertainty model; decision theory; normative approach; equivalent ideal observer; rational observer ID SIGNAL-DETECTION; LUMINANCE INCREMENT; SET-SIZE; MODEL; DETECTABILITY; UNCERTAINTY; BACKGROUNDS; ATTENTION; STIMULUS; PERFORMANCE AB There is a lack of consensus in measuring observer performance in search tasks. To pursue a consensus, we set our goal as to obtain metrics that are practical, meaningful and objective. We consider a metric practical if it can be implemented to measure human and computer observers' performance. To be meaningful, we propose to discover metrics that reflect the intrinsic properties of search observers. Thus, the meaningfulness of the metrics is ensured by the discovered properties being intrinsic. We set our success criteria as that the discovered properties can make verifiable predications. Thus the objectivity of the metrics is ensured by their prediction ability. The goal of this work is to present a theory and a conjecture toward two intrinsic properties of search observers: rationality in classification as measured by the location-known-exactly ROC curve and location uncertainty as measured by the effective set size. These two properties are used to develop search models in both single-response and free-response search tasks. To confirm whether these properties are "intrinsic", in a companion paper, we investigate their ability in predicting search performance of both human and scanning channelized Hotelling observers. C1 [He, Xin; Samuelson, Frank; Zeng, Rongping; Sahiner, Berkman] US FDA, Rockville, MD 20857 USA. RP He, X (reprint author), US FDA, Rockville, MD 20857 USA. NR 38 TC 0 Z9 0 U1 0 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 978-0-8194-9830-4 J9 PROC SPIE PY 2014 VL 9037 AR 903712 DI 10.1117/12.2043318 PG 11 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA7IZ UT WOS:000337585600036 ER PT S AU He, X Samuelson, F Sahiner, B AF He, Xin Samuelson, Frank Sahiner, Berkman BE MelloThoms, CR Kupinski, MA TI Discover Common Properties of Human Observers' Visual Search and Mathematical Observers' Scanning PART II. Empirical studies using human and model Observers SO MEDICAL IMAGING 2014: 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 FEB 16-17, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN Inc, Ventana Med Syst Inc, Intrace Med DE search; search performance; power-law-shaped ROC curve; uncertainty model of visual detection; decision theory; normative approach; equivalent ideal observer; rational observer; science as falsification AB In a companion paper, we proposed the well-delineated-object conjecture to describe a rational observer's behavior in a search task. We discovered two intrinsic properties to describe the performance of rational search observers: rationality in classification and location uncertainty. We proposed to use the location-known-exactly (LKE) ROC curve and the effective number of well-delineated objects or effective set size (M*) to quantify these two properties. The purpose of this paper is to develop an experimental framework to test the conjecture that was put forward in the companion paper. In particular, for each observer, we designed experiments to measure LIKE ROC curve and M*, which were then used to predict the same observer's performance in other search tasks. The predictions were then compared to the experimentally measured observer performance. Our results indicate that modeling the search performance using the LIKE ROC curve and M* leads to successful predictions in most cases. C1 [He, Xin; Samuelson, Frank; Sahiner, Berkman] US FDA, Rockville, MD 20857 USA. RP He, X (reprint author), US FDA, Rockville, MD 20857 USA. 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 978-0-8194-9830-4 J9 PROC SPIE PY 2014 VL 9037 AR 903713 DI 10.1117/12.2043319 PG 10 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA7IZ UT WOS:000337585600037 ER PT S AU Park, S Zhang, GZ Zeng, RP Myers, KJ AF Park, Subok Zhang, George Z. Zeng, Rongping Myers, Kyle J. BE MelloThoms, CR Kupinski, MA TI Comparing observer models and feature selection methods for a task-based statistical assessment of digital breast tomsynthesis in reconstruction space SO MEDICAL IMAGING 2014: 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 FEB 16-17, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN Inc, Ventana Med Syst Inc, Intrace Med DE model observer; technology assessment; channelized Hotelling observer; partial least squares; Laguerre Gauss; digital breast tomosynthesis; task-based assessment of image quality ID TOMOSYNTHESIS; PERFORMANCE; PROJECTION AB A task-based assessment of image quality(1) for digital breast tomosynthesis (DBT) can be done in either the projected or reconstructed data space. As the choice of observer models and feature selection methods can vary depending on the type of task and data statistics, we previously investigated the performance of two channelized-Hotelling observer models in conjunction with 2D Laguerre-Gauss (LG) and two implementations of partial least squares (PLS) channels along with that of the Hotelling observer in binary detection tasks involving DBT projections.(2, 3) The difference in these observers lies in how the spatial correlation in DBT angular projections is incorporated in the observer's strategy to perform the given task. In the current work, we extend our method to the reconstructed data space of DBT. We investigate how various model observers including the aforementioned compare for performing the binary detection of a spherical signal embedded in structured breast phantoms with the use of DBT slices reconstructed via filtered back projection. We explore how well the model observers incorporate the spatial correlation between different numbers of reconstructed DBT slices while varying the number of projections. For this, relatively small and large scan angles (24 degrees and 96 degrees) are used for comparison. Our results indicate that 1) given a particular scan angle, the number of projections needed to achieve the best performance for each observer is similar across all observer/channel combinations, i.e., N-p = 25 for scan angle 96 degrees and N-p = 13 for scan angle 24 degrees, and 2) given these sufficient numbers of projections, the number of slices for each observer to achieve the best performance differs depending on the channel/observer types, which is more pronounced in the narrow scan angle case. C1 [Park, Subok; Zhang, George Z.; Zeng, Rongping; Myers, Kyle J.] OSEL, CDRH, Div Imaging & Appl Math, 10903 New Hampshire Ave,Bldg 62,Rm 3109, Silver Spring, MD 20993 USA. RP Park, S (reprint author), OSEL, CDRH, Div Imaging & Appl Math, 10903 New Hampshire Ave,Bldg 62,Rm 3109, Silver Spring, MD 20993 USA. EM subok.park@fda.hhs.gov NR 18 TC 3 Z9 3 U1 0 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 978-0-8194-9830-4 J9 PROC SPIE PY 2014 VL 9037 AR UNSP 90370M DI 10.1117/12.2043598 PG 11 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA7IZ UT WOS:000337585600020 ER PT S AU Wunderlich, A Goossens, B AF Wunderlich, Adam Goossens, Bart BE MelloThoms, CR Kupinski, MA TI Nonparametric EROC analysis for observer performance evaluation on joint detection and estimation tasks SO MEDICAL IMAGING 2014: 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 FEB 16-17, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN Inc, Ventana Med Syst Inc, Intrace Med ID CURVES; AREAS AB The majority of the literature on task-based image quality assessment has focused on lesion detection tasks, using the receiver operating characteristic (ROC) curve, or related variants, to measure performance. However, since many clinical image evaluation tasks involve both detection and estimation (e. g., estimation of kidney stone composition, estimation of tumor size), there is a growing interest in performance evaluation for joint detection and estimation tasks. To evaluate observer performance on such tasks, Clarkson introduced the estimation ROC (EROC) curve, and the area under the EROC curve as a summary figure of merit. In the present work, we propose nonparametric estimators for practical EROC analysis from experimental data, including estimators for the area under the EROC curve and its variance. The estimators are illustrated with a practical example comparing MRI images reconstructed from different k-space sampling trajectories. C1 [Wunderlich, Adam] US FDA, Div Imaging & Appl Math, OSEL, CDRH, Rockville, MD 20857 USA. [Goossens, Bart] Univ Ghent, TELIN IPI iMinds, Dept Telecomm & Inform Proc, B-9000 Ghent, Belgium. RP Wunderlich, A (reprint author), US FDA, Div Imaging & Appl Math, OSEL, CDRH, Rockville, MD 20857 USA. EM adam.wunderlich@fda.hhs.gov; bart.goossens@telin.ugent.be NR 11 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 978-0-8194-9830-4 J9 PROC SPIE PY 2014 VL 9037 AR UNSP 90370F DI 10.1117/12.2043105 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA7IZ UT WOS:000337585600013 ER PT S AU Hammer, DX Lozzi, A Abliz, E Greenbaum, N Turner, KP Pfefer, TJ Agrawal, A Krauthamer, V Welle, CG AF Hammer, Daniel X. Lozzi, Andrea Abliz, Erkinay Greenbaum, Noah Turner, Kevin P. Pfefer, T. Joshua Agrawal, Anant Krauthamer, Victor Welle, Cristin G. BE Hirschberg, H Madsen, SJ Jansen, ED Luo, Q Mohanty, SK Thakor, NV TI Optical coherence microscopy of mouse cortical vasculature surrounding implanted electrodes SO OPTICAL TECHNIQUES IN NEUROSURGERY, NEUROPHOTONICS, AND OPTOGENETICS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Techniques in Neurosurgery, Neurophotonics, and Optogenetics CY FEB 01-04, 2014 CL San Francisco, CA SP SPIE DE Optical coherence tomography; angiography; microscopy; neural electrode; mouse; vasculature ID ANGIOGRAPHY; TETRAPLEGIA; TOMOGRAPHY; HUMANS; CORTEX AB Optical coherence microscopy (OCM) provides real-time, in-vivo, three-dimensional, isotropic micron-resolution structural and functional characterization of tissue, cells, and other biological targets. Optical coherence angiography (OCA) also provides visualization and quantification of vascular flow via speckle-based or phase-resolved techniques. Performance assessment of neuroprosthetic systems, which allow direct thought control of limb prostheses, may be aided by OCA. In particular, there is a need to examine the underlying mechanisms of chronic functional degradation of implanted electrodes. Angiogenesis, capillary network remodeling, and changes in flow velocity are potential indicators of tissue changes that may be associated with waning electrode performance. The overall goal of this investigation is to quantify longitudinal changes in vascular morphology and capillary flow around neural electrodes chronically implanted in mice. We built a 1315-nm OCM system to image vessels in neocortical tissue in a cohort of mice. An optical window was implanted on the skull over the primary motor cortex above a penetrating shank-style microelectrode array. The mice were imaged bi-weekly to generate vascular maps of the region surrounding the implanted microelectrode array. Acute effects of window and electrode implantation included vessel dilation and profusion of vessels in the superficial layer of the cortex (0-200 mu m). In deeper layers surrounding the electrode, no qualitative differences were seen in this early phase. These measurements establish a baseline vascular tissue response from the cortical window preparation and lay the ground work for future longitudinal studies to test the hypothesis that vascular changes will be associated with chronic electrode degradation. C1 [Hammer, Daniel X.; Lozzi, Andrea; Abliz, Erkinay; Greenbaum, Noah; Turner, Kevin P.; Pfefer, T. Joshua; Agrawal, Anant; Krauthamer, Victor; Welle, Cristin G.] US FDA, Div Phys, Off Sci & Engn Lab, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Hammer, DX (reprint author), US FDA, Div Phys, Off Sci & Engn Lab, Ctr Devices & Radiol Hlth, 10913 New Hampshire Ave, Silver Spring, MD 20993 USA. EM daniel.hammer@fda.hhs.gov OI Welle, Cristin/0000-0001-8735-0983 NR 18 TC 0 Z9 0 U1 0 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 978-0-8194-9841-0 J9 PROC SPIE PY 2014 VL 8928 AR 892804 DI 10.1117/12.2040972 PG 9 WC Microscopy; Optics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Microscopy; Optics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA BA7IR UT WOS:000337576500001 ER PT J AU Zhang, Q Davis, KJ Hoffmann, D Vaidya, VS Brown, RP Goering, PL AF Zhang, Qin Davis, Kelly J. Hoffmann, Dana Vaidya, Vishal S. Brown, Ronald P. Goering, Peter L. TI Urinary biomarkers track the progression of nephropathy in hypertensive and obese rats SO BIOMARKERS IN MEDICINE LA English DT Article DE chronic kidney disease; hypertension; obesity; urine biomarker ID ACUTE KIDNEY INJURY; CARDIAC-SURGERY; RENAL-DISEASE; KOLETSKY RAT; CYSTATIN C; NEPHROTOXICITY; ASSOCIATION; MOLECULE-1; EXCRETION; RECOVERY AB Aims:To determine whether urinary biomarkers of acute kidney injury can be used to monitor the progression of chronic kidney injury in a rat model of hypertension and obesity. Materials & methods: A suite of novel urinary biomarkers were used to track the progression of kidney damage in SHROB and SHR-lean rats. Results: Urinary albumin, NAG, clusterin, osteopontin, RPA-1 and fibrinogen levels were significantly elevated over time and were closely associated with the severity of histopathologically determined nephropathy in both SHROB and SHR-lean rats. Conclusion: Urinary biomarkers, such as albumin, fibrinogen, NAG, clusterin, RPA-1 and osteopontin, may serve as useful tools to track the progression of chronic kidney disease associated with hypertension and obesity. C1 [Zhang, Qin; Brown, Ronald P.; Goering, Peter L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Davis, Kelly J.] US FDA, Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Hoffmann, Dana; Vaidya, Vishal S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Hoffmann, Dana; Vaidya, Vishal S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Goering, PL (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM peter.goering@fda.hhs.gov FU Office of Chief Scientist Challenge Grant FX This work was supported by funds provided by an Office of Chief Scientist Challenge Grant, a program administered by the US FDA, Office of the Commissioner. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 36 TC 12 Z9 12 U1 1 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 EI 1752-0371 J9 BIOMARK MED JI Biomark. Med. PD JAN PY 2014 VL 8 IS 1 BP 85 EP 94 DI 10.2217/bmm.13.106 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AI9BF UT WOS:000337220700020 PM 24325231 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI The History of Intraocular Lenses SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Brint, Stephen F.] US FDA, LASIK Study, Rockville, MD 20857 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 9 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 3 EP 6 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800001 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI The Materials SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter ID METHACRYLATE) INTRAOCULAR LENSES C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Brint, Stephen F.] US FDA, LASIK Study, Rockville, MD 20857 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 6 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 7 EP 13 PG 7 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800002 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI Rigid Intraocular Lenses of the Past SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Brint, Stephen F.] US FDA, LASIK Study, Rockville, MD 20857 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 15 EP 16 PG 2 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800003 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI Soft Intraocular Lenses of the Past SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Brint, Stephen F.] US FDA, LASIK Study, Rockville, MD 20857 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 17 EP 22 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800004 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI Currently Used Lenses SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter ID SILICONE INTRAOCULAR LENSES; YAG LASER PHOTODISRUPTION; NEODYMIUM C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Brint, Stephen F.] US FDA, LASIK Study, Rockville, MD 20857 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 23 EP 26 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800005 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI Monofocal Intraocular Lenses SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter ID HIGHER-ORDER ABERRATIONS; CORNEAL; DECENTRATION C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Brint, Stephen F.] US FDA, LASIK Study, Rockville, MD 20857 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 9 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 27 EP 38 PG 12 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800006 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI Toric Intraocular Lenses SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter ID CORNEAL INCISION; ASTIGMATISM; PHACOEMULSIFICATION; LOCATION C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Brint, Stephen F.] US FDA, LASIK Study, Rockville, MD 20857 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 10 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 39 EP 52 PG 14 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800007 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI Multifocal Intraocular Lenses SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter ID AGE-RELATED MACULOPATHY; CONTRAST SENSITIVITY; VISUAL-ACUITY; BLUE-LIGHT; MACULAR DEGENERATION; SPHERICAL-ABERRATION; CATARACT-SURGERY; RETINAL DISEASE; SEE PROJECT; LOW-VISION C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Brint, Stephen F.] US FDA, LASIK Study, Rockville, MD 20857 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 45 TC 0 Z9 0 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 53 EP 72 PG 20 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800008 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI Accommodative Intraocular Lenses SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Brint, Stephen F.] US FDA, LASIK Study, Rockville, MD 20857 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 6 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 73 EP 78 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800009 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI Mix and Match SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Brint, Stephen F.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 79 EP 81 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800010 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI Refractive Cataract Surgery SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 7 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 83 EP 89 PG 7 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800011 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI Intraocular Lens Exchange SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 91 EP 94 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800012 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI Correction of Astigmatism SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter ID TORIC INTRAOCULAR-LENS; CATARACT-SURGERY; CORNEAL ASTIGMATISM; IMPLANTATION; OUTCOMES C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 7 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 95 EP 97 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800013 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI Vision Quality SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter ID MULTIFOCAL INTRAOCULAR LENSES; CONTRAST SENSITIVITY; SPHERICAL-ABERRATION; CATARACT-SURGERY; VISUAL-ACUITY; GLAUCOMA; EYES; ANISEIKONIA; POSITION; DISEASE C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 32 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 99 EP 118 PG 20 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800014 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI Viscoelastic Substances SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter ID RETENTION; HEALON C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 7 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 119 EP 124 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800015 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI Instruments Used for Intraocular Lens Insertion SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 125 EP 133 PG 9 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800016 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI Injectors and Implantation of Foldable Intraocular Lenses SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 135 EP 153 PG 19 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800017 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI Implantation of an Intraocular Lens With Capsular Rupture SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 6 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 155 EP 159 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800018 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI Tear or Damage of the Intraocular Lens SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 161 EP 162 PG 2 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800019 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI Irrigation/Aspiration Post Implantation SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 4 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 163 EP 166 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800020 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI Closure of the Incision SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 167 EP 170 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800021 ER PT B AU Buratto, L Brint, SF Boccuzzi, D AF Buratto, Lucio Brint, Stephen F. Boccuzzi, Domenico BA Buratto, L Brint, SF Boccuzzi, D BF Buratto, L Brint, SF Boccuzzi, D TI Drugs and Fluids for Intraocular Use SO CATARACT SURGERY AND INTRAOCULAR LENSES LA English DT Article; Book Chapter ID RANDOMIZED CLINICAL-TRIAL; BALANCED SALT-SOLUTION; BLOOD-AQUEOUS BARRIER; CATARACT-SURGERY; IRRIGATING SOLUTIONS; CORNEAL ENDOTHELIUM; POSTOPERATIVE ENDOPHTHALMITIS; PROPHYLAXIS; GLUTATHIONE; ESCRS C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Boccuzzi, Domenico] Clin Mediterranea, Naples, Italy. [Boccuzzi, Domenico] Comboni Ctr, Sogakope, Ghana. NR 19 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-604-9 PY 2014 BP 171 EP 173 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BA3PP UT WOS:000334564800022 ER PT J AU Hoffmann, M Zhao, SH Pettengill, J Luo, Y Monday, SR Abbott, J Ayers, SL Cinar, HN Muruvanda, T Li, C Allard, MW Whichard, J Meng, JH Brown, EW McDermott, PF AF Hoffmann, Maria Zhao, Shaohua Pettengill, James Luo, Yan Monday, Steven R. Abbott, Jason Ayers, Sherry L. Cinar, Hediye N. Muruvanda, Tim Li, Cong Allard, Marc W. Whichard, Jean Meng, Jianghong Brown, Eric W. McDermott, Patrick F. TI Comparative Genomic Analysis and Virulence Differences in Closely Related Salmonella enterica Serotype Heidelberg Isolates from Humans, Retail Meats, and Animals SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE outbreak; antimicrobial resistance; plasmid; SNP analysis; trace-back ID IV SECRETION SYSTEMS; MULTILOCUS GENOTYPE DATA; SEROVAR HEIDELBERG; ESCHERICHIA-COLI; UNITED-STATES; POPULATION-STRUCTURE; CAENORHABDITIS-ELEGANS; PLASMID; DIVERSITY; EVOLUTION AB Salmonella enterica subsp. enterica serovar Heidelberg (S. Heidelberg) is one of the top serovars causing human salmonellosis. Recently, an antibiotic-resistant strain of this serovar was implicated in a large 2011 multistate outbreak resulting from consumption of contaminated ground turkey that involved 136 confirmed cases, with one death. In this study, we assessed the evolutionary diversity of 44 S. Heidelberg isolates using whole-genome sequencing (WGS) generated by the 454 GS FLX (Roche) platform. The isolates, including 30 with nearly indistinguishable (one band difference) Xbal pulsed-field gel electrophoresis patterns (JF6X01.0032, JF6X01.0058), were collected from various sources between 1982 and 2011 and included nine isolates associated with the 2011 outbreak. Additionally, we determined the complete sequence for the chromosome and three plasmids from a clinical isolate associated with the 2011 outbreak using the Pacific Biosciences (PacBio) system. Using single-nucleotide polymorphism (SNP) analyses, we were able to distinguish highly clonal isolates, including strains isolated at different times in the same year. The isolates from the recent 2011 outbreak clustered together with a mean SNP variation of only 17 SNPs. The S. Heidelberg isolates carried a variety of phages, such as prophage P22, P4, lambda-like prophage Gifsy-2, and the P2-like phage which carries the sopE1 gene, virulence genes including 62 pathogenicity, and 13 fimbrial markers and resistance plasmids of the incompatibility (Inc)I1, IncA/C, and IncHI2 groups. Twenty-one strains contained an IncX plasmid carrying a type IV secretion system. On the basis of the recent and historical isolates used in this study, our results demonstrated that, in addition to providing detailed genetic information for the isolates, WGS can identify SNP targets that can be utilized for differentiating highly clonal S. Heidelberg isolates. C1 [Hoffmann, Maria; Zhao, Shaohua; Abbott, Jason; Ayers, Sherry L.; Li, Cong; McDermott, Patrick F.] US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. [Hoffmann, Maria; Meng, Jianghong] Univ Maryland, Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Pettengill, James; Luo, Yan] US FDA, Div Publ Hlth & Biostat, Off Food Def Commun & Emergency Response, Ctr Food Safety & Nutr, College Pk, MD USA. [Monday, Steven R.; Muruvanda, Tim; Allard, Marc W.; Brown, Eric W.] US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Nutr, College Pk, MD USA. [Cinar, Hediye N.] US FDA, Div Virulence Assessment, Off Appl Res & Safety Assessment, Ctr Food Safety & Nutr, Laurel, MD USA. [Whichard, Jean] Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Atlanta, GA USA. RP Hoffmann, M (reprint author), US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. EM maria.hoffman@fda.hhs.gov; Patrick.McDermott@fda.hhs.gov FU Center for Veterinary Medicine; Center for Food Safety and Applied Nutrition at the US Food and Drug Administration; Joint Institute for Food Safety and Applied Nutrition (JIFSAN), University of Maryland, College Park, MD FX The authors thank Ruth Timme for submission of the draft genomes to NCBI and the NCBI rapid annotation pipeline team, Bill Klimke, Dmitry Dernovoy, Stacy Ciufo, Kathleen O'Neill, Azat Badretdin, and Tatiana Tatusova, for key genome annotation service. Further they thank Yuansha Chen for sharing the CVM/DAFM database of antimicrobial resistance genes. No human subjects or animals were used in this study. All authors have read the manuscript and agreed to its contents, subject matter, and author line order. These data are novel and have not been previously published elsewhere. Disclosure forms provided by the authors will be available with the full text of this article. This work was supported by the Center for Veterinary Medicine and the Center for Food Safety and Applied Nutrition at the US Food and Drug Administration and by an appointment of MH by the Joint Institute for Food Safety and Applied Nutrition (JIFSAN), University of Maryland, College Park, MD. NR 64 TC 22 Z9 22 U1 0 U2 28 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2014 VL 6 IS 5 BP 1046 EP 1068 DI 10.1093/gbe/evu079 PG 23 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA AI7BY UT WOS:000337037100002 PM 24732280 ER PT B AU Goren, MJ Plaut, VC AF Goren, Matt J. Plaut, Victoria C. BE Thomas, KM Plaut, VC Tran, NM TI Racial Identity Denial and its Discontents Implications for Individuals and Organizations SO DIVERSITY IDEOLOGIES IN ORGANIZATIONS SE Series in Applied Psychology LA English DT Article; Book Chapter ID DOMINANT-GROUP IDENTITY; COLOR-BLINDNESS; WHITE PRIVILEGE; INTERGROUP RELATIONS; GROUP IDENTIFICATION; ETHNIC-IDENTITY; SELF-ESTEEM; DIVERSITY; ATTITUDES; PREJUDICE C1 [Goren, Matt J.] Univ Calif Berkeley, Social Personal Psychol Program, Berkeley, CA 94720 USA. [Goren, Matt J.] US FDA, Rockville, MD 20857 USA. [Plaut, Victoria C.] Berkeley Sch Law, Berkeley, CA USA. [Plaut, Victoria C.] Berkeley Sch Law, Culture Divers & Intergrp Relat Lab, Berkeley, CA USA. [Plaut, Victoria C.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. RP Goren, MJ (reprint author), Univ Calif Berkeley, Social Personal Psychol Program, Berkeley, CA 94720 USA. NR 111 TC 0 Z9 0 U1 1 U2 2 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-84872-966-7; 978-1-315-85218-8; 978-1-84872-965-0 J9 SER APPL PSYCHOL PY 2014 BP 43 EP 66 PG 24 WC Industrial Relations & Labor; Psychology, Applied SC Business & Economics; Psychology GA BA2HW UT WOS:000333423200005 ER PT S AU Dobrovolsky, VN Cao, XF Bhalli, JA Heflich, RH AF Dobrovolsky, Vasily N. Cao, Xuefei Bhalli, Javed A. Heflich, Robert H. BE Keohavong, P Grant, SG TI Detection of Pig-a Mutant Erythrocytes in the Peripheral Blood of Rats and Mice SO MOLECULAR TOXICOLOGY PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Gene mutation; Glycosyl phosphatidyl inositol; Flow cytometry; Reticulocytes; CD59 surface marker; CD24 surface marker; Antibodies ID FLOW-CYTOMETRIC DETECTION; IN-VIVO GENOTOXICITY; MUTATION ASSAY; TRANSGENIC MICE; SHUTTLE VECTORS; CELLS; GENE; MODEL; TOXICOLOGY; SELECTION AB The endogenous X-linked phosphatidyl inositol glycan class A gene (Pig-a) can be used as a reporter of in vivo somatic cell mutation in rats and mice. Pig-a mutant cells are deficient in specific protein surface markers and can be identified and quantified by immunofluorescent staining followed by high-throughput flow cytometry. Pig-a mutation detection is commonly performed with red blood cells (RBCs) because (1) the low volumes of blood required for determining mutant frequencies in RBCs allow multiple samplings on small laboratory animals over extended periods of time; (2) the execution of the RBC assay is easy and the interpretation of the results is straightforward; and (3) RBC Pig-a mutant frequencies are known within hours of sample collection. Two endpoints are determined in the assay: the frequency of mutant total RBCs and the frequency of mutant reticulocytes. When Pig-a mutation is used to assess the in vivo mutagenic potential of suspect hazards, the frequency of mutant reticulocytes is an early indicator of mutagenic potential, while the mutant frequency in total RBCs can be measured more rapidly and with greater precision. C1 [Dobrovolsky, Vasily N.; Cao, Xuefei; Bhalli, Javed A.; Heflich, Robert H.] Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Dobrovolsky, VN (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. NR 22 TC 3 Z9 4 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-739-6; 978-1-62703-738-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1105 BP 205 EP 221 DI 10.1007/978-1-62703-739-6_17 D2 10.1007/978-1-62703-739-6 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA BA2SX UT WOS:000333851000018 PM 24623231 ER PT S AU Dobrovolsky, VN Shaddock, JG Heflich, RH AF Dobrovolsky, Vasily N. Shaddock, Joseph G. Heflich, Robert H. BE Keohavong, P Grant, SG TI Analysis of In Vivo Mutation in the Hprt and Tk Genes of Mouse Lymphocytes SO MOLECULAR TOXICOLOGY PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Hypoxanthine-guanine phosphoribosyltransferase (Hprt); Thymidine kinase (Tk); alamarBlue (TM); Mutation; Loss of heterozygosity (LOH) ID CHINESE-HAMSTER CELLS; TRANSGENIC MICE; ADENINE PHOSPHORIBOSYLTRANSFERASE; SOMATIC MUTATION; LOCUS; HETEROZYGOSITY; INVIVO; ASSAY; SYSTEM; RECOMBINATION AB Assays measuring mutant frequencies in endogenous reporter genes are used for identifying potentially genotoxic environmental agents and discovering phenotypes prone to genomic instability and diseases, such as cancer. Here, we describe methods for identifying mouse spleen lymphocytes with mutations in the endogenous X-linked hypoxanthine guanine phosphoribosyl transferase (Hprt) gene and the endogenous autosomal thymidine kinase (Tk) gene. The selective clonal expansion of mutant lymphocytes is based upon the phenotypic properties of HPRT-and TK-deficient cells. The same procedure can be utilized for quantifying Hprt mutations in most strains of mice (and, with minor changes, in other mammalian species), while mutations in the Tk gene can be determined only in transgenic mice that are heterozygous for inactivation of this gene. Expanded mutant clones can be further analyzed to classify the types of mutations in the Tk gene (small intragenic mutations vs. large chromosomal mutations) and to determine the nature of intragenic mutation in both the Hprt and Tk genes. C1 [Dobrovolsky, Vasily N.; Shaddock, Joseph G.; Heflich, Robert H.] Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Dobrovolsky, VN (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. NR 39 TC 1 Z9 1 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-739-6; 978-1-62703-738-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1105 BP 255 EP 270 DI 10.1007/978-1-62703-739-6_20 D2 10.1007/978-1-62703-739-6 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA BA2SX UT WOS:000333851000021 PM 24623234 ER PT S AU Fuscoe, JC AF Fuscoe, James C. BE Keohavong, P Grant, SG TI Simultaneous Quantification of t(14;18) and HPRT Exon 2/3 Deletions in Human Lymphocytes SO MOLECULAR TOXICOLOGY PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Translocation; Deletion; Lymphocytes; V(D) J recombination; Illegitimate V(D) J recombination; HPRT deletions; t(14;18) translocation; Quantitative PCR assay Poisson statistics; Human; Cancer; Biomarker ID ILLEGITIMATE V(D)J RECOMBINATION; MEDIATED MUTATIONS; SEQUENCE-ANALYSIS; T-LYMPHOCYTES; ADULT HUMANS; DNA; ETOPOSIDE; LYMPHOMA; T(14-18); CELLS AB Specific recurring chromosomal translocations and deletions are found in a variety of cancers. In hematopoietic malignancies, many of these chromosomal aberrations result from mistakes involving V(D)J recombination. V(D)J recombination is required for the formation of functional T-cell receptor genes in T-cells and antibody genes in B-cells. This is an inherently dangerous process, however, because double-strand breaks are introduced into the chromosomes. Molecular evidence indicates that failure of the fidelity of this process results in the activation of proto-oncogenes or the inactivation of tumor-suppressor genes. Here we describe sensitive, quantitative PCR assays for the measurement of such events in human lymphocytes. One assay measures the frequency of t(14; 18) translocations that result in the dysfunctional regulation of the anti-apoptotic gene BCL-2. The other assay measures the frequency of a deletion caused by illegitimate V(D)J recombination in the X-linked HPRT gene. The findings and conclusions presented in this article are the author's and do not necessarily reflect those of the Food and Drug Administration. C1 US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Fuscoe, JC (reprint author), US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-739-6; 978-1-62703-738-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1105 BP 303 EP 311 DI 10.1007/978-1-62703-739-6_24 D2 10.1007/978-1-62703-739-6 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA BA2SX UT WOS:000333851000025 PM 24623238 ER PT S AU Myers, MB McKinzie, PB Wang, YY Meng, FX Parsons, BL AF Myers, Meagan B. McKinzie, Page B. Wang, Yiying Meng, Fanxue Parsons, Barbara L. BE Keohavong, P Grant, SG TI ACB-PCR Quantification of Somatic Oncomutation SO MOLECULAR TOXICOLOGY PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Allele-specific competitive blocker-polymerase chain reaction (ACB-PCR); Oncomutation; Point mutation; Allele-specific PCR; Mutation detection; Base substitution; KRAS ID COMPETITIVE BLOCKER PCR; RAS CODON 61; MUTANT FRACTION; TUMOR; MUTATION; CANCER; TISSUE AB Allele-specific competitive blocker-polymerase chain reaction (ACB-PCR) is a sensitive approach for the selective amplification of an allele. Using the ACB-PCR technique, hotspot point mutations in oncogenes and tumor-suppressor genes (oncomutations) are being developed as quantitative biomarkers of cancer risk. ACB-PCR employs a mutant specific primer (with a 3'-penultimate mismatch relative to the mutant DNA sequence, but a double 3'-terminal mismatch relative to the wild-type DNA sequence) to selectively amplify rare mutant DNA molecules. A blocker primer (having a non-extendable 3'-end and with a 3'-penultimate mismatch relative to the wild-type DNA sequence, but a double 3'-terminal mismatch relative to the mutant DNA sequence) is included in ACB-PCR to selectively repress amplification from the abundant wild-type molecules. Consequently, ACB-PCR is capable of quantifying the level of a single basepair substitution mutation in a DNA population when present at a mutant: wild type ratio of 10(-5) or greater. Quantification of rare mutant alleles is achieved by parallel analysis of unknown samples and mutant fraction (MF) standards (defined mixtures of mutant and wild-type DNA sequences). The ability to quantify specific mutations with known association to cancer has several important applications, including evaluating the carcinogenic potential of chemical exposures in rodent models and in the diagnosis and treatment of cancer. This chapter provides a step-by-step description of the ACB-PCR methodology as it has been used to measure human KRAS codon 12 GGT to GAT mutation. C1 [Myers, Meagan B.] Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA. [McKinzie, Page B.; Wang, Yiying; Meng, Fanxue; Parsons, Barbara L.] Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Myers, MB (reprint author), Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA. NR 24 TC 2 Z9 2 U1 0 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-739-6; 978-1-62703-738-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1105 BP 345 EP 363 DI 10.1007/978-1-62703-739-6_27 D2 10.1007/978-1-62703-739-6 PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA BA2SX UT WOS:000333851000028 PM 24623241 ER PT J AU Robertson, A Garcia, AC Quintana, HAF Smith, TB Castillo, BF Reale-Munroe, K Gulli, JA Olsen, DA Hooe-Rollman, JI Jester, ELE Klimek, BJ Plakas, SM AF Robertson, Alison Garcia, Ana C. Quintana, Harold A. Flores Smith, Tyler B. Castillo, Bernard F., II Reale-Munroe, Kynoch Gulli, Joseph A. Olsen, David A. Hooe-Rollman, Jennifer I. Jester, Edward L. E. Klimek, Brian J. Plakas, Steven M. TI Invasive Lionfish (Pterois volitans): A Potential Human Health Threat for Ciguatera Fish Poisoning in Tropical Waters SO MARINE DRUGS LA English DT Article DE ciguatera fish poisoning; Caribbean ciguatoxins; lionfish; Caribbean; mass spectrometry ID CIGUATOXIN; CHANNEL; TOXINS; BREVETOXINS; ATLANTIC AB Invasive Indo-Pacific lionfish (Pterois volitans) have rapidly expanded in the Western Atlantic over the past decade and have had a significant negative impact on reef fish biodiversity, habitat, and community structure, with lionfish out-competing native predators for resources. In an effort to reduce this population explosion, lionfish have been promoted for human consumption in the greater Caribbean region. This study examined whether the geographical expansion of the lionfish into a known ciguatera-endemic region can pose a human health threat for ciguatera fish poisoning (CFP). More than 180 lionfish were collected from waters surrounding the US Virgin Islands throughout 2010 and 2011. Ciguatoxin testing included an in vitro neuroblastoma cytotoxicity assay for composite toxicity assessment of sodium-channel toxins combined with confirmatory liquid chromatography tandem mass spectrometry. A 12% prevalence rate of ciguatoxic lionfish exceeding the FDA guidance level of 0.1 mu g/kg C-CTX-1 equivalents was identified in fish from the U. S. Virgin Islands, highlighting a potential consumption risk in this region. This study presents the first evidence that the invasive lionfish, pose a direct human health risk for CFP and highlights the need for awareness and research on this food safety hazard in known endemic areas. C1 [Robertson, Alison; Garcia, Ana C.; Quintana, Harold A. Flores; Hooe-Rollman, Jennifer I.; Jester, Edward L. E.; Klimek, Brian J.; Plakas, Steven M.] US FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. [Robertson, Alison; Klimek, Brian J.] Univ S Alabama, Dept Marine Sci, Mobile, AL 36688 USA. [Smith, Tyler B.] Univ Virgin Islands, Ctr Marine & Environm Studies, St Thomas, VI 00802 USA. [Castillo, Bernard F., II; Reale-Munroe, Kynoch] Univ,Virgin Islands, Coll Sci & Math, Kingshill, VI 00850 USA. [Gulli, Joseph A.] Caribbean Ocean Restorat & Educ CORE Fdn, Christiansted, VI 00824 USA. [Olsen, David A.] St Thomas Fishermens Assoc, St Thomas, VI 00803 USA. RP Robertson, A (reprint author), US FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, 1 Iberville Dr, Dauphin Isl, AL 36528 USA. EM alisonrobertson@southalabama.edu; agarci3@gmail.com; Harold.FloresQuintana@fda.hhs.gov; tsmith@live.uvi.edu; bcastil@live.uvi.edu; kynoch_reale@yahoo.com; nolionfish@yahoo.com; Olsen41@aol.com; Jennifer.Hooe-Rollman@fda.hhs.gov; Edward.Jester@fda.hhs.gov; bklimek15@gmail.com; Steven.Plakas@fda.hhs.gov FU Centers for Disease Control and Prevention, National Center for Environmental Health [U01EH000421]; Ecology and Oceanography of Harmful Algal Blooms (ECOHAB) program through the National Oceanic and Atmospheric Administration (NOAA) [NA11NOS4780028, NA11NOS4780062] FX We are grateful for the assistance of the many volunteer divers and fishermen who assisted with collection of lionfish specimens during this study. Lionfish photographs were kindly provided by one of our volunteer divers, Robert Georgopul and used with permission. We are thankful to Jared Loader (FDA-ORISE) for helpful discussions and input on the chemistry of CTXs and to Elizabeth Kadison for sample co-ordination in St. Thomas. Jessica Hill and Elise Koob assisted with sample preparation. The Dauphin Island Sea Laboratory-FDA co-operative program provided internships to Jessica Hill, Elise Koob, and co-author Brian Klimek. This work was supported in part by funding from the Centers for Disease Control and Prevention, National Center for Environmental Health grant U01EH000421, and by the Ecology and Oceanography of Harmful Algal Blooms (ECOHAB) program through the National Oceanic and Atmospheric Administration (NOAA) grants NA11NOS4780028 and NA11NOS4780062. This is ECOHAB contribution no. 766. NR 21 TC 9 Z9 11 U1 2 U2 38 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-3397 J9 MAR DRUGS JI Mar. Drugs PD JAN PY 2014 VL 12 IS 1 BP 88 EP 97 DI 10.3390/md12010088 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AH4HH UT WOS:000336087500006 PM 24378919 ER PT S AU Benvenuto, MA Ahuja, S Duncan, T Noonan, GO Roberts-Kirchhoff, E AF Benvenuto, M. A. Ahuja, S. Duncan, T. Noonan, G. O. Roberts-Kirchhoff, E. BE Benvenuto, MA Ahuja, S Duncan, TV Noonan, GO RobertsKirchhoff, ES TI Overview SO CHEMISTRY OF FOOD, FOOD SUPPLEMENTS, AND FOOD CONTACT MATERIALS: FROM PRODUCTION TO PLATE SE ACS Symposium Series LA English DT Editorial Material; Book Chapter AB Ensuring the safety of food requires a complex and ever-changing set of interactions between producers, distrbutors, consumers and regulators. As advances are made in packaging and food additives, as food distributions systems evolve to meet consumer needs, or as these respond to environmental and population changes, adjustments to regulatory systems may become neceesary. Analytical, environmental and materials chemistry can often play important roles in responding to these changes and in continuing to help with the improvement of food safety and security. This chapter gives a breif overview of the chapters, produced from seminars presented at three symposia held at the 245th ACS National Convention in New Orleans, Louisiana in the spring of 2013. C1 [Benvenuto, M. A.; Roberts-Kirchhoff, E.] Univ Detroit Mercy, Detroit, MI 48221 USA. [Ahuja, S.] UNC Wilmington, Ahuja Acad Water Qual, Wilmington, NC USA. [Duncan, T.] US FDA, Bedford Pk, IL 60516 USA. [Noonan, G. O.] US FDA, College Pk, MD 20740 USA. RP Benvenuto, MA (reprint author), Univ Detroit Mercy, 4001 W McNichols Rd, Detroit, MI 48221 USA. EM Gregory.Noonan@fda.hhs.gov NR 13 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-2952-5 J9 ACS SYM SER JI ACS Symp. Ser. PY 2014 VL 1159 BP 1 EP 4 D2 10.1021/bk-2014-1159 PG 4 WC Food Science & Technology SC Food Science & Technology GA BA4MI UT WOS:000336002500001 ER PT S AU Croce, TA AF Croce, Teresa A. BE Benvenuto, MA Ahuja, S Duncan, TV Noonan, GO RobertsKirchhoff, ES TI FDA's Regulation of Nanotechnology in Food Ingredients SO CHEMISTRY OF FOOD, FOOD SUPPLEMENTS, AND FOOD CONTACT MATERIALS: FROM PRODUCTION TO PLATE SE ACS Symposium Series LA English DT Article; Book Chapter AB Nanotechnology has the potential to impact many FDA-regulated product areas, including food ingredients. The agency issued draft guidance in 2011 to address its current thinking on nanotechnology and has extended that overarching guidance through the publication of a subsequent draft guidance document in 2012 specific to food ingredients, including food contact substances and food ingredients that are color additives. The 2012 document examines how significant changes in manufacturing process, including the integration of nanotechnology, may impact the safety and regulatory status of the food ingredient. C1 US FDA, Div Petit Review, Off Food Addit Safety, College Pk, MD 20740 USA. RP Croce, TA (reprint author), US FDA, Div Petit Review, Off Food Addit Safety, 5100 Paint Branch Pkwy,HFS 265, College Pk, MD 20740 USA. EM Teresa.Croce@fda.hhs.gov NR 6 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-2952-5 J9 ACS SYM SER JI ACS Symp. Ser. PY 2014 VL 1159 BP 41 EP 50 D2 10.1021/bk-2014-1159 PG 10 WC Food Science & Technology SC Food Science & Technology GA BA4MI UT WOS:000336002500004 ER PT J AU Pang, L Word, B Xu, JS Wang, HG Hammons, G Huang, SM Lyn-Cook, B AF Pang, Li Word, Beverly Xu, Joshua Wang, Honggang Hammons, George Huang, Shiew-Mei Lyn-Cook, Beverly TI ATP-Binding Cassette Genes Genotype and Expression: A Potential Association with Pancreatic Cancer Development and Chemoresistance? SO GASTROENTEROLOGY RESEARCH AND PRACTICE LA English DT Article ID MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; CELL-LINES; MDR1 GENE; POLYMORPHISMS; TRANSPORTERS; SUSCEPTIBILITY; CHEMOTHERAPY; LOCALIZATION; GEMCITABINE AB Genetic polymorphisms in ABC (ATP-binding cassette) transporter genes are associated with differential responses to chemotherapy in various cancers including pancreatic cancer. In this study, four SNPs in the ABCB1, ABCC1, and ABCG2 genes were investigated in normal and pancreatic cancerous specimens. The expression of the three transporters was also analyzed. The TT genotypes of G2677T and C3435T in ABCB1 gene were associated with lower risk of developing pancreatic cancer (P = 0.013, OR = 0.35 and P = 0.015, OR = 0.29, resp.). To our knowledge, this is the first report of the common polymorphisms in the ABCB1 gene affecting the genetic risk of developing pancreatic cancer. Moreover, the expression of ABCB1 in 2677TT and 3435TT carriers was lower compared to the wild-type homozygotes and heterozygotes. A cell viability assay, using standard pancreatic cancer cell lines, revealed that the ABCB1 2677TT-3455TT haplotype was more sensitive than the other haplotypes to gemcitabine. Conclusion. Polymorphisms in ABCB1 G2677T and G3435T were associated with differential susceptibility to pancreatic cancer and may predict responses to chemotherapy. C1 [Pang, Li; Word, Beverly; Wang, Honggang; Hammons, George; Lyn-Cook, Beverly] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Xu, Joshua] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Huang, Shiew-Mei] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat Res, Silver Spring, MD 20993 USA. RP Lyn-Cook, B (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM beverly.lyn-cook@fda.hhs.gov OI Xu, Joshua/0000-0001-5313-5847 NR 28 TC 3 Z9 3 U1 1 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-6121 EI 1687-630X J9 GASTROENT RES PRACT JI Gastroenterol. Res. Pract. PY 2014 AR 414931 DI 10.1155/2014/414931 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AH5DW UT WOS:000336149700001 ER PT J AU Zhang, MH Feng, L Gu, JF Ma, L Qin, D Wu, C Jia, XB AF Zhang, Minghua Feng, Liang Gu, Junfei Ma, Liang Qin, Dong Wu, Chan Jia, Xiaobin TI The Attenuation of Moutan Cortex on Oxidative Stress for Renal Injury in AGEs-Induced Mesangial Cell Dysfunction and Streptozotocin-Induced Diabetic Nephropathy Rats SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY LA English DT Article ID GLYCATION END-PRODUCTS; KIDNEY-DISEASE; ANTIOXIDANT ACTIVITY; GENE-EXPRESSION; HIGH-GLUCOSE; RECEPTOR; COMPLICATIONS; INFLAMMATION; RAGE; PATHOGENESIS AB Oxidative stress (OS) has been regarded as one of themajor pathogeneses of diabetic nephropathy (DN) through damaging kidney which is associated with renal cells dysfunction. The aim of this study was to investigate whether Moutan Cortex (MC) could protect kidney function against oxidative stress in vitro or in vivo. The compounds in MC extract were analyzed by HPLC-ESI-MS. High-glucose-fat diet and STZ (30 mg kg(-1)) were used to induce DN rats model, while 200 mu g mL(-1) AGEs were for HBZY-1 mesangial cell damage. The treatment with MC could significantly increase the activity of SOD, glutathione peroxidase (GSH-PX), and catalase (CAT). However, lipid peroxidation malondialdehyde (MDA) was reduced markedly in vitro or in vivo. Furthermore, MC decreased markedly the levels of blood glucose, serum creatinine, and urine protein in DN rats. Immunohistochemical assay showed that MC down regulated significantly transforming growth factor beta 2 (TGF-beta 2) protein expression in renal tissue. Our data provided evidence to support this fact that MC attenuated OS in AGEs-induced mesangial cell dysfunction and also in high-glucose-fat diet and STZ-induced DN rats. C1 [Zhang, Minghua; Feng, Liang; Gu, Junfei; Ma, Liang; Qin, Dong; Wu, Chan; Jia, Xiaobin] Jiangsu Prov Acad Chinese Med, Key Lab New Drug Delivery Syst Chinese Mat Med, Nanjing 210028, Jiangsu, Peoples R China. [Zhang, Minghua; Qin, Dong; Jia, Xiaobin] Jiangsu Univ, Dept Pharm, Zhenjiang 212013, Jiangsu, Peoples R China. [Gu, Junfei; Wu, Chan; Jia, Xiaobin] Nanjing Univ Chinese Med, Coll Pharm, Nanjing 210046, Jiangsu, Peoples R China. [Ma, Liang] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Feng, L (reprint author), Jiangsu Prov Acad Chinese Med, Key Lab New Drug Delivery Syst Chinese Mat Med, Nanjing 210028, Jiangsu, Peoples R China. EM wenmoxiushi@163.com; jxiaobin2005@hotmail.com FU National Natural Science of China [81202906]; Natural Science Foundation of Jiangsu Province [BK2012491] FX The authors sincerely acknowledge the financial support of National Natural Science of China (no. 81202906) and Natural Science Foundation of Jiangsu Province (BK2012491). NR 49 TC 1 Z9 1 U1 3 U2 9 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1942-0900 EI 1942-0994 J9 OXID MED CELL LONGEV JI Oxidative Med. Cell. Longev. PY 2014 AR 463815 DI 10.1155/2014/463815 PG 13 WC Cell Biology SC Cell Biology GA AG9JL UT WOS:000335735300001 ER PT J AU Scott, J Botsis, T Ball, R AF Scott, J. Botsis, T. Ball, R. TI Simulating adverse event spontaneous reporting systems as preferential attachment networks SO APPLIED CLINICAL INFORMATICS LA English DT Article DE Simulation; data mining; vaccines; safety; network analysis ID SIGNAL GENERATION; US VACCINE; PHARMACOVIGILANCE; INTUSSUSCEPTION; VAERS AB Background: Spontaneous Reporting Systems [SRS] are critical tools in the post-licensure evaluation of medical product safety. Regulatory authorities use a variety of data mining techniques to detect potential safety signals in SRS databases. Assessing the performance of such signal detection procedures requires simulated SRS databases, but simulation strategies proposed to date each have limitations. Objective: We sought to develop a novel SRS simulation strategy based on plausible mechanisms for the growth of databases over time. Methods: We developed a simulation strategy based on the network principle of preferential attachment. We demonstrated how this strategy can be used to create simulations based on specific databases of interest, and provided an example of using such simulations to compare signal detection thresholds for a popular data mining algorithm. Results: The preferential attachment simulations were generally structurally similar to our targeted SRS database, although they had fewer nodes of very high degree. The approach was able to generate signal-free SRS simulations, as well as mimicking specific known true signals. Explorations of different reporting thresholds for the FDA Vaccine Adverse Event Reporting System suggested that using proportional reporting ratio [PRR] > 3.0 may yield better signal detection operating characteristics than the more commonly used PRR > 2.0 threshold. Discussion: The network analytic approach to SRS simulation based on the principle of preferential attachment provides an attractive framework for exploring the performance of safety signal detection algorithms. This approach is potentially more principled and versatile than existing simulation approaches. Conclusion: The utility of network-based SRS simulations needs to be further explored by evaluating other types of simulated signals with a broader range of data mining approaches, and comparing network-based simulations with other simulation strategies where applicable. C1 [Scott, J.; Botsis, T.; Ball, R.] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Botsis, T.] Univ Tromso, Dept Comp Sci, Tromso, Norway. RP Scott, J (reprint author), US FDA, Off Biostat & Epidemiol, CBER, 1401 Rockville Pike,HFM 215, Rockville, MD 20852 USA. EM john.scott@fda.hhs.gov NR 16 TC 4 Z9 4 U1 0 U2 2 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 1869-0327 J9 APPL CLIN INFORM JI Appl. Clin. Inform. PY 2014 VL 5 IS 1 BP 206 EP 218 DI 10.4338/ACI-2013-11-RA-0097 PG 13 WC Medical Informatics SC Medical Informatics GA AG6XG UT WOS:000335561700003 PM 24734134 ER PT J AU Sharma, K Goehe, R Beckta, JM Valerie, K Gewirtz, DA AF Sharma, Khushboo Goehe, Rachel Beckta, Jason M. Valerie, Kristoffer Gewirtz, David A. TI AUTOPHAGY AND RADIOSENSITIZATION IN CANCER SO EXCLI JOURNAL LA English DT Review DE Autophagy; ATM; DNA damage response; lung cancer; glioblastomas; breast cancer; radiosensitization ID CELL LUNG-CANCER; MALIGNANT GLIOMA-CELLS; GROWTH-FACTOR RECEPTOR; UNFOLDED PROTEIN RESPONSE; DNA-DAMAGE RESPONSE; BREAST-TUMOR CELLS; IONIZING-RADIATION; CYTOTOXIC AUTOPHAGY; SIGNALING PATHWAYS; MAMMALIAN TARGET AB Autophagy is a natural self-degradative process by which cells eliminate misfolded proteins and damaged organelles. Autophagy has been shown to have multiple functions in tumor cells that may be dependent on the tumor type and the treatment conditions. Autophagy can have a cytoprotective role and be thought of as a survival mechanism or be cytotoxic in nature and mediate cell death. Radiation, one of the primary treatments for many different types of cancer, almost uniformly promotes autophagy in tumor cells. While autophagy produced in response to radiation is often considered to be cytoprotective, radiation-induced autophagy has also been shown to mediate susceptibility to radiation. This review addresses the complexity of autophagy in response to radiation treatment in three different cancer models, specifically lung cancer, breast cancer and glioblastoma. A deeper understanding of the different roles played by autophagy in response to radiation should facilitate the development of approaches for enhancing the therapeutic utility of radiation by providing strategies for combination treatment with unique radiosensitizers as well as preventing the initiation of strategies which are likely to attenuate the effectiveness of radiation therapy. C1 [Sharma, Khushboo; Gewirtz, David A.] Virginia Commonwealth Univ, Dept Pharmacol, Richmond, VA 23298 USA. [Sharma, Khushboo; Gewirtz, David A.] Virginia Commonwealth Univ, Dept Toxicol, Richmond, VA 23298 USA. [Beckta, Jason M.; Valerie, Kristoffer] Virginia Commonwealth Univ, Dept Radiat Oncol, Richmond, VA 23298 USA. [Gewirtz, David A.] Virginia Commonwealth Univ, Dept Med, Richmond, VA 23298 USA. [Valerie, Kristoffer; Gewirtz, David A.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23298 USA. [Goehe, Rachel] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Gewirtz, DA (reprint author), Virginia Commonwealth Univ, Massey Canc Ctr, 401 Coll St, Richmond, VA 23298 USA. EM gewirtz@vcu.edu FU NIH [R01NS064593, R21ES016636, F30 CA171893]; CTSA from the National Center for Advancing Translational Sciences [UL1TR000058] FX Supported in part by NIH R01NS064593 (K.V.), R21ES016636 (K.V.), F30 CA171893 (J.M.B.) and CTSA award No. UL1TR000058 from the National Center for Advancing Translational Sciences (D.A.G). NR 75 TC 5 Z9 5 U1 0 U2 4 PU EXCLI JOURNAL MANAGING OFFICE PI DORTMUND PA LEIBNIZ RESEARCH CENTRE WORKING ENVIRONMENT & HUMAN FACTORS EXCLI JOURNAL, ARDEYSTR 67, DORTMUND, D-44139, GERMANY SN 1611-2156 J9 EXCLI J JI EXCLI J. PY 2014 VL 13 BP 178 EP 191 PG 14 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AG6HK UT WOS:000335519500014 PM 26417252 ER PT S AU Le, HND Hitchins, VM Ilev, IK Kim, DH AF Le, Hanh N. D. Hitchins, Victoria M. Ilev, Ilko K. Kim, Do-Hyun BE Gannot, I TI Monitoring Biofilm Attachment on Medical Device Surfaces Using Hyperspectral Imaging SO OPTICAL FIBERS AND SENSORS FOR MEDICAL DIAGNOSTICS AND TREATMENT APPLICATIONS XIV SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications XIV CY FEB 01-02, 2014 CL San Francisco, CA SP SPIE DE Biofilm attachment; Hyperspectral Imaging; Dot Product Method ID INFECTION; ADHERENCE AB Microbial biofilm is a colony of single bacteria cells (planktonic) that attach to surfaces, attract other microorganisms to attach and grow, and together build an extracellular matrix composed of polysaccharides, protein, and DNA. Furthermore, some cells may detach and spread to other surface. Biofilm on medical devices can cause severe infection to all age ranges from infant to adult. Therefore, it is important to detect biofilm in a fast and efficient manner. Hyperspectral Imaging was utilized for distinguishing a wide area of biofilm coverage on various materials and on different textures of stainless steel test coupons. In addition to biofilm coverage, the shear stress of biofilm on attached surfaces is also important. The present study investigates the effect of shear stress on the adhesion of biofilms on common medical device surfaces such as glass, polycarbonate, polytetrafluoroethylene, and stainless steel with different textures. Biofilm was grown using Pseudomonas aeruginosa and growth was monitored after 24 and 48 hours at 37 degrees C. The coupons covered with biofilm were tilted at 45 degrees and 90 degrees for 30 seconds to induce shear stress and Hyperspectral Images were taken. We hypothesize that stronger attachment on rough surface withstands greater shear stress compared to smooth surface. The results have verified our hypothesis with more biofilm persists on brushed surface such as stainless steel than on un-brushed surface like mirror-like or glass. C1 [Le, Hanh N. D.; Hitchins, Victoria M.; Ilev, Ilko K.; Kim, Do-Hyun] US FDA, Silver Spring, MD 20993 USA. RP Le, HND (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Do-Hyun.Kim@fda.hhs.gov NR 11 TC 1 Z9 1 U1 0 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 978-0-8194-9851-9 J9 PROC SPIE PY 2014 VL 8938 AR 893809 DI 10.1117/12.2047867 PG 10 WC Remote Sensing; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Remote Sensing; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA3CA UT WOS:000334100600005 ER PT S AU Gould, T Wang, QZ Pfefer, TJ AF Gould, Taylor Wang, Quanzeng Pfefer, T. Joshua BE Raghavachari, R Liang, R TI Optical-thermal light-tissue interactions during photoacoustic imaging SO DESIGN AND QUALITY FOR BIOMEDICAL TECHNOLOGIES VII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Design and Quality for Biomedical Technologies VII CY FEB 01-02, 2014 CL San Francisco, CA SP SPIE DE Photoacoustics; Monte Carlo modeling; laser-tissue interactions; laser safety ID PORT-WINE STAINS; OXYGEN-SATURATION; LASER TREATMENT; HUMAN SKIN; IN-VIVO; BREAST; TOMOGRAPHY; RECONSTRUCTION; SPECTROSCOPY; IRRADIATION AB Photoacoustic imaging (PAI) has grown rapidly as a biomedical imaging technique in recent years, with key applications in cancer diagnosis and oximetry. In spite of these advances, the literature provides little insight into thermal tissue interactions involved in PAI. To elucidate these basic phenomena, we have developed, validated, and implemented a three-dimensional numerical model of tissue photothermal (PT) response to repetitive laser pulses. The model calculates energy deposition, fluence distributions, transient temperature and damage profiles in breast tissue with blood vessels and generalized perfusion. A parametric evaluation of these outputs vs. vessel diameter and depth, optical beam diameter, wavelength, and irradiance, was performed. For a constant radiant exposure level, increasing beam diameter led to a significant increase in subsurface heat generation rate. Increasing vessel diameter resulted in two competing effects - reduced mean energy deposition in the vessel due to light attenuation and greater thermal superpositioning due to reduced thermal relaxation. Maximum temperatures occurred either at the surface or in subsurface regions of the dermis, depending on vessel geometry and position. Results are discussed in terms of established exposure limits and levels used in prior studies. While additional experimental and numerical study is needed, numerical modeling represents a powerful tool for elucidating the effect of PA imaging devices on biological tissue. C1 [Gould, Taylor; 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 40 TC 0 Z9 0 U1 0 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 978-0-8194-9849-6 J9 PROC SPIE PY 2014 VL 8936 AR 893603 DI 10.1117/12.2044379 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA3BX UT WOS:000334099600002 ER PT S AU Wang, JT Coburn, J Woolsey, N Liang, CP Ramella-Roman, J Chen, Y Pfefer, J AF Wang, Jianting Coburn, James Woolsey, Nicholas Liang, Chia-Pin Ramella-Roman, Jessica Chen, Yu Pfefer, Joshua BE Raghavachari, R Liang, R TI Quantitative Assessment of Biophotonic Imaging System Performance with Phantoms Fabricated by Rapid Prototyping SO DESIGN AND QUALITY FOR BIOMEDICAL TECHNOLOGIES VII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Design and Quality for Biomedical Technologies VII CY FEB 01-02, 2014 CL San Francisco, CA SP SPIE DE 3D printing; rapid proto-typing; geometric phantoms; biophotonic imaging; hyperspectral reflectance imaging ID OPTICAL-PROPERTIES; IN-VITRO; TISSUES AB In biophotonic imaging, turbid phantoms that are low-cost, biologically-relevant, and durable are desired for standardized performance assessment. Such phantoms often contain inclusions of varying depths and sizes in order to quantify key image quality characteristics such as penetration depth, sensitivity and contrast detectability. The emerging technique of rapid prototyping with three-dimensional (3D) printers provides a potentially revolutionary way to fabricate these structures. Towards this goal, we have characterized the optical properties and morphology of phantoms fabricated by two 3D printing approaches: thermosoftening and photopolymerization. Material optical properties were measured by spectrophotometry while the morphology of phantoms incorporating 0.2-1.0 mm diameter channels was studied by mu CT, optical coherence tomography (OCT) and optical microscopy. A near-infrared absorbing dye and nanorods at several concentrations were injected into channels to evaluate detectability with a near-infrared hyperspectral reflectance imaging (HRI) system (650-1100 nm). Phantoms exhibited biologically-relevant scattering and low absorption across visible and near-infrared wavelengths. Although limitations in resolution were noted, channels with diameters of 0.4 mm or more could be reliably fabricated. The most significant problem noted was the porosity of phantoms generated with the thermosoftening-based printer. The aforementioned three imaging methods provided a valuable mix of insights into phantom morphology and may also be useful for detailed structural inspection of medical devices fabricated by rapid prototyping, such as customized implants. Overall, our findings indicate that 3D printing has significant potential as a method for fabricating well-characterized, standard phantoms for medical imaging modalities such as HRI. C1 [Wang, Jianting; Woolsey, Nicholas; Liang, Chia-Pin; Chen, Yu] Univ Maryland, College Pk, MD 20742 USA. [Wang, Jianting; Coburn, James; Woolsey, Nicholas; Chen, Yu; Pfefer, Joshua] Food & Drug Adm, Silver Spring, MD 10903 USA. [Ramella-Roman, Jessica] Florida Int Univ, Dept Biomed Engn, Miami, FL 33174 USA. RP Wang, JT (reprint author), Univ Maryland, College Pk, MD 20742 USA. FU National Science Foundation's FDA [CBET-1238407]; University of Maryland; Center for Excellence in Regulatory Science and Innovation (CERSI) FX The authors acknowledge support from the National Science Foundation's FDA Scholar-in-Residence program (NSF, CBET-1238407) and the University of Maryland Center for Excellence in Regulatory Science and Innovation (CERSI). The authors would also like to thank Dr. Maureen Dreher for her help with mu CT imaging. NR 14 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 978-0-8194-9849-6 J9 PROC SPIE PY 2014 VL 8936 AR UNSP 89360M DI 10.1117/12.2044089 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA3BX UT WOS:000334099600012 ER PT J AU Hamburg, MA AF Hamburg, Margaret A. TI A Key Port of the FDA Mission: Driving Innovation SO MANUFACTURING ENGINEERING LA English DT Editorial Material C1 US FDA, Washington, DC 20204 USA. RP Hamburg, MA (reprint author), US FDA, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC MANUFACTURING ENGINEERS PI DEARBORN PA ONE SME DRIVE, PO BOX 930, DEARBORN, MI 48121-0930 USA SN 0361-0853 J9 MANUF ENG JI Manuf. Eng. PY 2014 SU S BP 19 EP 19 PG 1 WC Engineering, Manufacturing SC Engineering GA AE4EV UT WOS:000333936500003 ER PT J AU Neese, SL Pisani, SL Doerge, DR Helferich, WG Sepehr, E Chittiboyina, AG Rotte, SCK Smillie, TJ Khan, IA Korol, DL Schantz, SL AF Neese, Steven L. Pisani, Samantha L. Doerge, Daniel R. Helferich, William G. Sepehr, Estatira Chittiboyina, Amar G. Rotte, Sateesh Chandra Kumar Smillie, Troy J. Khan, Ikhlas A. Korol, Donna L. Schantz, Susan L. TI The effects of dietary treatment with S-equol on learning and memory processes in middle-aged ovariectomized rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Equol; Phytoestrogens; Aging; Executive function; Place teaming ID ESTROGEN-RECEPTOR-ALPHA; ADULT FEMALE RATS; POSTMENOPAUSAL WOMEN; SPATIAL MEMORY; COGNITIVE FUNCTION; SOY PHYTOESTROGENS; DEVELOPMENTAL NEUROTOXICITY; DIFFERENTIAL REINFORCEMENT; ISOFLAVONE SUPPLEMENTS; DELAYED ALTERNATION AB The use of over-the-counter botanical estrogens containing isolated soy isoflavones, including genistein and daidzein, has become a popular alternative to traditional hormone therapies. Menopausal women use these products as an aide in healthy aging, including for the maintenance of cognitive function. The safety and efficacy of many of these commercial preparations remain unknown. Previous research in our lab found that treatment of ovariectomized (OVX) female Long-Evans rats with genistein impaired working memory in an operant delayed spatial alternation (DSA) task and response learning in a plus-maze, but enhanced place learning assessed in the plus-maze. The present study further examined the effects of isolated isoflavones on working memory and place learning by treating middle-aged (12-13 month old) OVX female Long-Evans rats with S-equol, the exclusive enantiomer produced by metabolism of daidzein in the mammalian gut. S-equol binds selectively to ERI3 with an affinity similar to that of genistein but has low transcriptional potency. For DSA testing, S-equol at 1.94, 0.97 mg, or 0 mg (sucrose control) was orally administered to animals daily, 30 min before behavioral testing, and again both 4 and 8 hours after the first treatment Rats were tested on the DSA task following the first, morning dose. For place learning, rats received 0.97 mg S-equol every 4 hours during the light portion of the cycle beginning 48 hours prior to behavioral testing (total exposure 8.7 mg S-equol). S-equol treatment was largely without effect on the DSA and place learning tasks. This is the first study to test the behavioral effects of isolated S-equol in OVX rodents, and shows that, unlike genistein or estradiol, repeated daily treatment with this isoflavone metabolite does not alter learning and memory processes in middle-aged OVX rats. (c) 2013 Elsevier Inc All rights reserved. C1 [Neese, Steven L.; Schantz, Susan L.] Univ Illinois, Dept Comparat Biosci, Urbana, IL 61802 USA. [Neese, Steven L.; Pisani, Samantha L.; Korol, Donna L.; Schantz, Susan L.] Univ Illinois, Neurosci Program, Urbana, IL 61801 USA. [Neese, Steven L.] Baldwin Wallace Univ, Dept Psychol & Neurosci, Berea, OH 44017 USA. [Doerge, Daniel R.; Sepehr, Estatira] 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. [Chittiboyina, Amar G.; Rotte, Sateesh Chandra Kumar; Smillie, Troy J.; Khan, Ikhlas A.] Univ Mississippi, Natl Ctr Nat Prod Res, Thad Cochran Res Ctr 3011, University, MS 38677 USA. [Korol, Donna L.] Syracuse Univ, Dept Biol, Syracuse, NY 13244 USA. RP Neese, SL (reprint author), Baldwin Wallace Univ, Dept Psychol & Neurosci, 275 Eastland Rd, Berea, OH 44017 USA. EM stlneese@illinois.edu; spisan2@illinois.edu; daniel.doerge@fda.hhs.org; helferic@illinois.edu; estatira.sepehr@fda.hhs.gov; amar@olemiss.edu; sckumarr@olemiss.edu; tsmillie@olemiss.edu; ikhan@olemiss.edu; dlkorol@syr.edu; schantz@illinois.edu FU ODS [P50 AT006268]; NCAAM; NCI; National Institute of Environmental Health Sciences [T32 ES007326] FX The authors would like to thank Mindy Howe and Suren Bandara for their help with OVX surgeries and daily animal care and John Katzenellebogen for reviewing this manuscript. This research was supported by the P50 AT006268 from ODS, NCAAM, and NCI (DLK, SLS, DRD, WGH). Steven Neese also received support from the National Institute of Environmental Health Sciences Grant T32 ES007326. NR 82 TC 4 Z9 4 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 EI 1872-9738 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JAN-FEB PY 2014 VL 41 BP 80 EP 88 DI 10.1016/j.ntt.2013.12.004 PG 9 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA AE4IW UT WOS:000333947100012 PM 24368316 ER PT J AU Fine, AJ Sorbello, A Kortepeter, C Scarazzini, L AF Fine, Andrew J. Sorbello, Alfred Kortepeter, Cindy Scarazzini, Linda TI Progressive Multifocal Leukoencephalopathy after Natalizumab Discontinuation SO ANNALS OF NEUROLOGY LA English DT Article ID MULTIPLE-SCLEROSIS; PATIENT; RISK AB Objective: To identify cases of laboratory-or biopsy-confirmed progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis (MS) who previously discontinued natalizumab (NTZ) for reasons unrelated to suspected or proven PML and assess PML risk factors in these cases. Methods: We searched the US Food and Drug Administration Adverse Event Reporting System and MEDLINE for reports submitted from 2006 to 2012 of laboratory-confirmed PML with symptom onset >= 30 days following NTZ withdrawal. We only analyzed cases where NTZ discontinuation was unrelated to suspected PML. Results: Seventeen patients discontinued NTZ for reasons unrelated to PML but were subsequently diagnosed with the disease. The median NTZ duration was 47 monthly doses (range = 9-59 doses). All patients presented with compatible clinical symptoms within 6 months following withdrawal, and PML was confirmed by brain biopsy or by identifying JC virus in the cerebrospinal fluid by polymerase chain reaction. Immune reconstitution inflammatory syndrome (IRIS) was reported in 11 patients. Eleven patients (65%) received new MS treatments between NTZ discontinuation and PML confirmation. No deaths were reported. At NTZ withdrawal, 16 patients (94%) had >= 1 PML risk factor, including NTZ duration >= 2 years (n = 13), prior immunosuppressive agents (n = 8), and reported anti-JC virus seropositivity (n = 13). Interpretation: NTZ-treated patients presenting clinically with PML within 6 months after NTZ withdrawal frequently have pre-existing PML risk factors. Clinicians need heightened awareness for new onset PML, IRIS, and MS relapse in evaluating neurological decline following NTZ discontinuation. C1 [Fine, Andrew J.; Sorbello, Alfred; Kortepeter, Cindy] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Fine, AJ (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Andrew.Fine@fda.hhs.gov NR 18 TC 23 Z9 23 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2014 VL 75 IS 1 BP 108 EP 115 DI 10.1002/ana.24051 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AA3WQ UT WOS:000331026300012 PM 24242357 ER PT J AU Miesegaes, GR Lute, SC Read, EK Brorson, KA AF Miesegaes, G. R. Lute, S. C. Read, E. K. Brorson, K. A. TI Viral Clearance by Flow-Through Mode Ion Exchange Columns and Membrane Adsorbers SO BIOTECHNOLOGY PROGRESS LA English DT Article DE monoclonal antibodies; viral clearance; anion exchange chromatography; membrane adsorbers; downstream purification; design-of-experiments; DoE ID VIRUS REMOVAL; CHROMATOGRAPHY; PURIFICATION; PROTEIN; ANTIBODIES; ROBUST; MEDIA; DNA AB Anion exchange (AEX) is a common downstream purification operation for biotechnology products manufactured in cell culture such as therapeutic monoclonal antibodies (mAbs) and Fc-fusion proteins. We present a head-to-head comparison of the viral clearance efficiency of AEX adsorbers and column chromatography using the same process fluids and comparable run conditions. We also present overall trends from the CDER viral clearance database. In our comparison of multiple brands of resins and adsorbers, clearance of three model viruses (PPV, X-MuLV, and PR772) was largely comparable, with some exceptions which may reflect run conditions that had not been optimized on a resin/membrane specific basis. (c) 2013 American Institute of Chemical Engineers Biotechnol. Prog., 30:124-131, 2014 C1 [Miesegaes, G. R.; Lute, S. C.; Read, E. K.; Brorson, K. A.] CDER FDA, Off Biotechnol Prod, Silver Spring, MD 20903 USA. RP Brorson, KA (reprint author), CDER FDA, Off Biotechnol Prod, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA. EM kurt.brorson@fda.hhs.gov FU CDER Regulatory Science and Research project [11-64] FX The authors thank Michele Dougherty and Audey Jia for careful review of this manuscript. Funding was provided by the CDER Regulatory Science and Research project grant 11-64. NR 31 TC 3 Z9 3 U1 2 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8756-7938 EI 1520-6033 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD JAN PY 2014 VL 30 IS 1 BP 124 EP 131 DI 10.1002/btpr.1832 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA AA9AJ UT WOS:000331385800013 PM 24167103 ER PT J AU Bento, JC Lane, KD Read, EK Cerca, N Christie, GE AF Bento, Joana C. Lane, Kristin D. Read, Erik K. Cerca, Nuno Christie, Gail E. TI Sequence determinants for DNA packaging specificity in the S-aureus pathogenicity island SaPI1 SO PLASMID LA English DT Article DE Pathogenicity island; SaPI; Terminase; DNA packaging; Helper phage; Pac site ID CAPSID SIZE DETERMINATION; GRAM-POSITIVE BACTERIA; HELPER PHAGE; PROTEINS; SITE; BACTERIOPHAGES; INTERFERENCE; REPLICATION; RECOGNITION; INITIATION AB The SaPIs and their relatives are a family of genomic islands that exploit helper phages for high frequency horizontal transfer. One of the mechanisms used by SaPIs to accomplish this molecular piracy is the redirection of the helper phage DNA packaging machinery. SaPls encode a small terminase subunit that can be substituted for that of the phage. In this study we have determined the initial packaging cleavage sites for helper phage 80a, which uses the phage-encoded small terminase subunit, and for SaPI1, which uses the SaPI-encoded small terminase subunit. We have identified a 19 nt SaPI1 sequence that is necessary and sufficient to allow high frequency 80a transduction of a plasmid by a terminase carrying the SaPI1-encoded small subunit. We also show that the hybrid enzyme with the SaPI1 small terminase subunit is capable of generalized transduction. (C) 2014 Elsevier Inc. All rights reserved. C1 [Bento, Joana C.; Lane, Kristin D.; Christie, Gail E.] Virginia Commonwealth Univ, Sch Med, Dept Microbiol & Immunol, Richmond, VA 23298 USA. [Read, Erik K.] Food & Drug Adm, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Silver Spring, MD 20993 USA. [Bento, Joana C.; Cerca, Nuno] Univ Minho, Ctr Biol Engn, IBB, P-4710057 Braga, Portugal. RP Christie, GE (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Microbiol & Immunol, POB 980678, Richmond, VA 23298 USA. EM jcbento@vcu.edu; lanekd@vcu.edu; Erik.Read@fda.hhs.gov; nunocerca@ceb.uminho.pt; christie@vcu.edu OI Cerca, Nuno/0000-0003-3365-3537 FU FDA's Medical Countermeasures Initiative [HHSF2232010000521]; NIH [1R56 AI081837]; Portuguese Institute Fundacao para a Ciencia e Tecnologia (FCT); PhD Fellowship [SFRH/BD/66250/2009]; National Academies National Research Council; NIAID/NIFI [HHSN272200700055C] FX This work was performed in part under FDA's Medical Countermeasures Initiative, Contract #HHSF2232010000521 and NIH 1R56 AI081837 (to GEC). JCB was supported by the Portuguese Institute Fundacao para a Ciencia e Tecnologia (FCT), PhD Fellowship SFRH/BD/66250/2009. E.K.R. was supported by the National Academies National Research Council; his contribution to this study was carried out at NICHHD, NIH, Bethesda, MD, in the laboratory of the late Robert A. Weisberg. Plasmid pCN51 (in strain NRS613) and strain RN4282 (NRS145) were obtained through the Network of Antimicrobial Resistance in Staphylococcus aureus (NARSA) program supported under NIAID/NIFI contract #HHSN272200700055C. NR 36 TC 5 Z9 5 U1 0 U2 3 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 2014 VL 71 BP 8 EP 15 PG 8 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA AC0MG UT WOS:000332188800002 PM 24365721 ER PT J AU Vorvolakos, K Coburn, JC Saylork, DM AF Vorvolakos, Katherine Coburn, James C. Saylork, David M. TI Dynamic interfacial behavior of viscoelastic aqueous hyaluronic acid: effects of molecular weight, concentration and interfacial velocity SO SOFT MATTER LA English DT Article ID PRIMARY CILIARY DYSKINESIA; NAKED MOLE-RAT; MECHANICAL-PROPERTIES; PERICELLULAR MATRIX; CONTACT INHIBITION; CANCER RESISTANCE; CELL-MIGRATION; HYDROGELS; ADHESION; MOTION AB An aqueous hyaluronic acid (HA((aq))) pericellular coat, when mediating the tactile aspect of cellular contact inhibition, has three tasks: interface formation, mechanical signal transmission and interface separation. To quantify the interfacial adhesive behavior of HA((aq)), we induce simultaneous interface formation and separation between HA((aq)) and a model hydrophobic, hysteretic Si-SAM surface. While surface tension gamma remains essentially constant, interface formation and separation depend greatly on concentration (5 <= C <= 30 mg mL(-1)), molecular weight (6 <= MW <= 2000 kDa) and interfacial velocity (0 <= V <= 3 mm s-1), each of which affect shear elastic and loss moduli G' and G '', respectively. Viscoelasticity dictates the mode of interfacial motion: wetting-dewetting, capillary necking, or rolling. Wetting-dewetting is quantified using advancing and receding contact angles theta(A) and theta(R), and the hysteresis between them, yielding data landscapes for each C above the [MW, V] plane. The landscape sizes, shapes, and curvatures disclose the interplay, between surface tension and viscoelasticity, which governs interfacial dynamics. Gel point coordinates modulus G and angular frequency omega appear to predict wetting-dewetting (G < 75 omega(0.2)), capillary necking (75 omega(0.2) < G < 200 omega(0.075)) or rolling (G > 200 omega(0.075)). Dominantly dissipative HA((aq)) sticks to itself and distorts irreversibly before separating, while dominantly elastic HA((aq)) makes contact and separates with only minor, reversible distortion. We propose the dimensionless number (G'V)/(omega,gamma), varying from similar to 10(-5) to similar to 10(3) in this work, as a tool to predict the mode of interface formation-separation by relating interfacial kinetics with bulk viscoelasticity. Cellular contact inhibition may be thus aided or compromised by physiological or interventional shifts in [C, MW, V], and thus in (G'V)/(omega,gamma), which affect both mechanotransduction and interfacial dynamics. These observations, understood in terms of physical properties, may be broadened to probe interfacial dynamics of other viscoelastic aqueous biopolymers. C1 [Vorvolakos, Katherine; Saylork, David M.] US FDA, Div Chem & Mat Sci, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. RP Vorvolakos, K (reprint author), US FDA, Div Chem & Mat Sci, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. EM katherine.vorvolakos@fda.hhs.gov FU Medical Device Fellowship Program of the Center for Devices and Radiological Health in United States Food and Drug Administration; Division of Chemistry and Material Science in the Office of Science and Engineering Laboratories, of the Center for Devices and Radiological Health in the United States Food and Drug Administration FX This work was supported by the Medical Device Fellowship Program, and by the Division of Chemistry and Material Science in the Office of Science and Engineering Laboratories, of the Center for Devices and Radiological Health in the United States Food and Drug Administration. We thank Professor Srinivasa R. Raghavan of the University of Maryland Department of Chemical and Biomolecular Engineering for guidance on rheometry. We also thank Dr Steven Pollack, Dr Peter Nemes and Dr Charles Durfor for helpful discussions. NR 52 TC 2 Z9 2 U1 1 U2 27 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1744-683X EI 1744-6848 J9 SOFT MATTER JI Soft Matter PY 2014 VL 10 IS 13 BP 2304 EP 2312 DI 10.1039/c3sm52372a PG 9 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Multidisciplinary; Polymer Science SC Chemistry; Materials Science; Physics; Polymer Science GA AC4GJ UT WOS:000332478800022 PM 24795963 ER PT J AU Lin, BH Guthrie, J Rahkovsky, I Lin, CT Lee, JY AF Lin, Biing-Hwan Guthrie, Joanne Rahkovsky, Ilya Lin, Chung-Tung Lee, Jonq-Ying TI Simulating the Potential Effects of a Shelf-Tag Nutrition Information Program and Pricing on Diet Quality Associated with Ready-to-Eat Cereals SO INTERNATIONAL FOOD AND AGRIBUSINESS MANAGEMENT REVIEW LA English DT Article DE breakfast cereals; Guiding Stars Program; pricing intervention; dietary outcomes ID FOOD-PRICES; PURCHASES; DEMAND; POLICY AB Previous research has shown that the Guiding Stars Program (TM) (GSP), a shelf-tag nutrition information system used in some supermarkets in the United States (US), increases consumer demand for ready-to-eat (RTE) breakfast cereals that the program considers more nutritious. Further, consumer demand for cereals is found to respond to price. Here we simulate potential changes in RTE cereal consumption predicted by estimated demand if a GSP or a 10% price manipulation were in effect nationwide in the US, and measure the impact on intakes of whole grains, added sugars, sodium, and calories. We find small effects for the GSP and somewhat larger ones for a 10% price intervention. C1 [Lin, Biing-Hwan; Guthrie, Joanne; Rahkovsky, Ilya] Econ Res Serv USDA, Washington, DC 20024 USA. [Lin, Chung-Tung] Ctr Food Safety & Appl Nutr FDA, College Pk, MD 20740 USA. [Lee, Jonq-Ying] Univ Florida, Dept Food & Resource Econ, Gainesville, FL 32611 USA. RP Lin, BH (reprint author), Econ Res Serv USDA, 355 E St SW, Washington, DC 20024 USA. EM blin@ers.usda.gov; jguthrie@ers.usda.gov; irahkovsky@ers.usda.gov; chung-tung.lin@fda.hhs.gov; jonqying@ufl.edu NR 33 TC 0 Z9 0 U1 0 U2 7 PU INT FOOD & AGRIBUSINESS MANAGEMENT REVIEW PI COLLEGE STATION PA 333 BLOCKER BUILDING, 2124 TAMU, COLLEGE STATION, TX 77843-2124 USA SN 1559-2448 J9 INT FOOD AGRIBUS MAN JI Int. Food Agribus. Manag. Rev. PY 2014 VL 17 IS A SI SI BP 7 EP 23 PG 17 WC Agricultural Economics & Policy SC Agriculture GA AB7VD UT WOS:000331998100002 ER PT J AU Darpo, B Sarapa, N Garnett, C Benson, C Dota, C Ferber, G Jarugula, V Johannesen, L Keirns, J Krudys, K Ortemann-Renon, C Riley, S Rogers-Subramaniam, D Stockbridge, N AF Darpo, Borje Sarapa, Nenad Garnett, Christine Benson, Charles Dota, Corina Ferber, Georg Jarugula, Venkateswar Johannesen, Lars Keirns, James Krudys, Kevin Ortemann-Renon, Catherine Riley, Steve Rogers-Subramaniam, Danise Stockbridge, Norman TI The IQ-CSRC Prospective Clinical Phase 1 Study: "Can Early QT Assessment Using Exposure Response Analysis Replace the Thorough QT Study?" SO ANNALS OF NONINVASIVE ELECTROCARDIOLOGY LA English DT Article DE Thorough QT; QTc study; QTc interval; healthy volunteers; single-ascending-dose ID HEALTHY-SUBJECTS; DE-POINTES; QT/QTC; PROLONGATION; INTERVAL; DATABASE; DRUGS AB A collaboration between the Consortium for Innovation and Quality in Pharmaceutical Development and the Cardiac Safety Research Consortium has been formed to design a clinical study in healthy subjects demonstrating that the thorough QT (TQT) study can be replaced by robust ECG monitoring and exposure-response (ER) analysis of data generated from First-in-Man single ascending dose (SAD) studies. Six marketed drugs with well-characterized QTc effects were identified in discussions with FDA; five have caused QT prolongation above the threshold of regulatory concern. Twenty healthy subjects will be enrolled in a randomized, placebo-controlled study designed with the intent to have similar power to exclude small QTc effects as a SAD study. Two doses (low and high) of each drug will be given on separate, consecutive days to 9 subjects. Six subjects will receive placebo. Data will be analyzed using linear mixed-effects ER models. Criteria for QT-positive drugs will be the demonstration of an upper bound (UB) of the 2-sided 90% confidence interval (CI) of the projected QTc effect at the peak plasma level of the lower dose above the threshold of regulatory concern (currently 10 ms) and a positive slope of ER relationship. The criterion for QT-negative drug will be an UB of the CI of the projected QTc effect of the higher dose <10 ms. It is expected that a successful outcome in this study will provide evidence supporting replacement of the TQT study with ECG assessments in standard early clinical development studies for a new chemical entity. C1 [Darpo, Borje] Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Div Cardiovasc Med, Stockholm, Sweden. [Darpo, Borje] iCardiac Technol, Rochester, NY USA. [Sarapa, Nenad] Bayer Healthcare Inc, Clin Sci, Whippany, NJ USA. [Garnett, Christine] Certara, St Louis, MO USA. [Benson, Charles; Rogers-Subramaniam, Danise] Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. [Dota, Corina] AstraZeneca R&D, Molndal, Sweden. [Ferber, Georg] Stat Georg Ferber GmbH, CH-4125 Riehen, Switzerland. [Jarugula, Venkateswar] Novartis Inst Biomed Res, Drug Metab & Pharmacokinet, E Hanover, NJ USA. [Johannesen, Lars; Krudys, Kevin] US FDA, Div Pharmacometr, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Johannesen, Lars] Karolinska Univ Hosp, Karolinska Inst, Dept Clin Physiol, Stockholm, Sweden. [Keirns, James] Astellas Pharma Global Dev Inc, Global Clin Pharmacol & Exploratory Dev, Northbrook, IL USA. [Ortemann-Renon, Catherine] Clin & Exploratory Pharmacol, Bridgewater, MA USA. [Riley, Steve] Pfizer Inc, Specialty Care Business Unit, Clin Pharmacol, Groton, CT 06340 USA. [Stockbridge, Norman] US FDA, Ctr Drug Evaluat & Res, Div Cardiovasc & Renal Prod, Silver Spring, MD USA. RP Darpo, B (reprint author), Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Div Cardiovasc Med, Stockholm, Sweden. EM borje.darpo@telia.com NR 21 TC 35 Z9 36 U1 0 U2 1 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 2014 VL 19 IS 1 BP 70 EP 81 DI 10.1111/anec.12128 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA5OC UT WOS:000331148300010 PM 24372708 ER PT S AU Ke, AB Rostami-Hodjegan, A Zhao, P Unadkat, JD AF Ke, Alice Ban Rostami-Hodjegan, Amin Zhao, Ping Unadkat, Jashvant D. BE Insel, PA TI Pharmacometrics in Pregnancy: An Unmet Need SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 54 SE Annual Review of Pharmacology and Toxicology LA English DT Review; Book Chapter DE modeling; simulation; PBPK; CYP; POP-PK ID INTERINDIVIDUAL VARIABILITY; PHARMACOKINETIC MODEL; FALCIPARUM-MALARIA; CLINICAL-TRIALS; DRUG TRIALS; WOMEN; FETAL; PRESCRIPTION; DISPOSITION; METABOLISM AB Pregnant women and their fetuses are orphan populations with respect to the safety and efficacy of drugs. Physiological and absorption, distribution, metabolism, and excretion (ADME) changes during pregnancy can significantly affect drug pharmacokinetics (PK) and may necessitate dose adjustment. Here, the specific aspects related to the design, execution, and analysis of clinical studies in pregnant women are discussed, underlining the unmet need for top-down pharmacometrics analyses and bottom-up modeling approaches. The modeling tools that support data analysis for the pregnancy population are reviewed, with a focus on physiologically based pharmacokinetics (PBPK) and population pharmacokinetics (POP-PK). By integrating physiological data, preclinical data, and clinical data (e.g., via POP-PK) to quantify anticipated changes in the PK of drugs during pregnancy, the PBPK approach allows extrapolation beyond the previously studied model drugs to other drugs with well-characterized ADME characteristics. Such a systems pharmacology approach can identify drugs whose PK may be altered during pregnancy, guide rational PK study design, and support dose adjustment for pregnant women. C1 [Ke, Alice Ban] Lilly Res Labs, Drug Disposit, Indianapolis, IN 46285 USA. [Rostami-Hodjegan, Amin] Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester M13 9PT, Lancs, England. [Rostami-Hodjegan, Amin] Simcyp Ltd, Sheffield S2 4SU, S Yorkshire, England. [Zhao, Ping] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Unadkat, Jashvant D.] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA. RP Ke, AB (reprint author), Lilly Res Labs, Drug Disposit, Indianapolis, IN 46285 USA. EM zamek_ban_alice@lilly.com; amin.rostami@manchester.ac.uk; Ping.Zhao@fda.hhs.gov; jash@u.washington.edu NR 55 TC 15 Z9 15 U1 0 U2 13 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0362-1642 BN 978-0-8243-0454-6 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2014 VL 54 BP 53 EP 69 DI 10.1146/annurev-pharmtox-011613-140009 PG 17 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BJR57 UT WOS:000329822200004 PM 24392692 ER PT J AU Natanegara, F Neuenschwander, B Seaman, JW Kinnersley, N Heilmann, CR Ohlssen, D Rochester, G AF Natanegara, Fanni Neuenschwander, Beat Seaman, John W., Jr. Kinnersley, Nelson Heilmann, Cory R. Ohlssen, David Rochester, George TI The current state of Bayesian methods in medical product development: survey results and recommendations from the DIA Bayesian Scientific Working Group SO PHARMACEUTICAL STATISTICS LA English DT Article ID CLINICAL-TRIALS; P-VALUES; STATISTICS; MODELS; ELICITATION; INFERENCE; BELIEFS; IDEAS C1 [Natanegara, Fanni; Heilmann, Cory R.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Neuenschwander, Beat] Novartis Pharma AG, Basel, Switzerland. [Seaman, John W., Jr.] Baylor Univ, Dept Stat Sci, Waco, TX 76798 USA. [Kinnersley, Nelson] Roche Prod Ltd, Welwyn Garden City AL7 3AY, Herts, England. [Ohlssen, David] Novartis Pharmaceut, E Hanover, NJ USA. [Rochester, George] US FDA, Ctr Tobacco Prod, Silver Sprint, MD USA. RP Natanegara, F (reprint author), Eli Lilly & Co, Indianapolis, IN 46285 USA. EM natanegara_fanni@lilly.com NR 49 TC 2 Z9 2 U1 0 U2 3 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 PY 2014 VL 13 IS 1 SI SI BP 3 EP 12 PG 10 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA AA3NW UT WOS:000331000400002 PM 24027093 ER PT J AU Price, KL Xia, HA Lakshminarayanan, M Madigan, D Manner, D Scott, J Stamey, JD Thompson, L AF Price, Karen L. Xia, H. Amy Lakshminarayanan, Mani Madigan, David Manner, David Scott, John Stamey, James D. Thompson, Laura TI Bayesian methods for design and analysis of safety trials SO PHARMACEUTICAL STATISTICS LA English DT Article ID SAMPLE-SIZE DETERMINATION; CLINICAL-TRIALS; CARDIOVASCULAR RISK; EVENT TIMES; FACTOR-VIII; METAANALYSIS; DISTRIBUTIONS; MODELS; CHOICE C1 [Price, Karen L.; Manner, David] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Xia, H. Amy] Amgen Inc, Thousand Oaks, CA 91320 USA. [Lakshminarayanan, Mani] Merck Res Labs, N Wales, PA USA. [Madigan, David] Columbia Univ, Dept Stat, New York, NY USA. [Scott, John] US FDA, Ctr Biol Evaluat & Res, Off Biostatist & Epidemiol, Silver Spring, MD USA. [Stamey, James D.] Baylor Univ, Dept Stat, Waco, TX 76798 USA. [Thompson, Laura] US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Silver Spring, MD USA. RP Price, KL (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Global Stat Sci & Adv Analyt, Indianapolis, IN 46285 USA. EM price_k@lilly.com OI Stamey, James/0000-0002-3787-6490 NR 65 TC 5 Z9 5 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 PY 2014 VL 13 IS 1 SI SI BP 13 EP 24 PG 12 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA AA3NW UT WOS:000331000400003 PM 23897858 ER PT J AU Gamalo, MA Tiwari, RC LaVange, LM AF Gamalo, Meg A. Tiwari, Ram C. LaVange, Lisa M. TI Bayesian approach to the design and analysis of non-inferiority trials for anti-infective products SO PHARMACEUTICAL STATISTICS LA English DT Article ID VENTILATOR-ASSOCIATED PNEUMONIA; HOSPITAL-ACQUIRED PNEUMONIA; INFECTIOUS-DISEASES SOCIETY; POWER PRIOR DISTRIBUTIONS; CLINICAL-TRIALS; PHARMACOKINETICS-PHARMACODYNAMICS; NONPARAMETRIC PROBLEMS; ANTIBACTERIAL AGENTS; NOSOCOMIAL PNEUMONIA; PREDICTIVE APPROACH C1 [Gamalo, Meg A.; Tiwari, Ram C.; LaVange, Lisa M.] US FDA, Off Biostat, Silver Spring, MD 20993 USA. RP Gamalo, MA (reprint author), US FDA, Off Biostat, Silver Spring, MD 20993 USA. EM margaret.gamalo@fda.hhs.gov NR 53 TC 12 Z9 12 U1 3 U2 14 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 PY 2014 VL 13 IS 1 SI SI BP 25 EP 40 PG 16 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA AA3NW UT WOS:000331000400004 PM 23913880 ER PT J AU Viele, K Berry, S Neuenschwander, B Amzal, B Chen, F Enas, N Hobbs, B Ibrahim, JG Kinnersley, N Lindborg, S Micallef, S Roychoudhury, S Thompson, L AF Viele, Kert Berry, Scott Neuenschwander, Beat Amzal, Billy Chen, Fang Enas, Nathan Hobbs, Brian Ibrahim, Joseph G. Kinnersley, Nelson Lindborg, Stacy Micallef, Sandrine Roychoudhury, Satrajit Thompson, Laura TI Use of historical control data for assessing treatment effects in clinical trials SO PHARMACEUTICAL STATISTICS LA English DT Article ID POWER PRIOR DISTRIBUTIONS; SAMPLE-SIZE; MODELS; INFORMATION C1 [Viele, Kert; Berry, Scott] Berry Consultants, Austin, TX 78746 USA. [Neuenschwander, Beat] Novartis Pharmaceut, CIS, Basel, Switzerland. [Amzal, Billy] LA SER Analyt, London, England. [Chen, Fang] SAS, Cary, NC USA. [Enas, Nathan] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Hobbs, Brian] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ibrahim, Joseph G.] Univ N Carolina, Chapel Hill, NC USA. [Kinnersley, Nelson] F Hoffmann La Roche & Cie AG, Welwyn Garden City, Herts, England. [Lindborg, Stacy] Biogen Idec Inc, Cambridge, MA USA. [Micallef, Sandrine] Sanofi Aventis R&D, Paris, France. [Roychoudhury, Satrajit] Novartis, E Hanover, NJ USA. [Thompson, Laura] US FDA, Rockville, MD 20857 USA. RP Viele, K (reprint author), Berry Consultants, Austin, TX 78746 USA. EM kert@berryconsultants.net FU NCI NIH HHS [P01 CA142538, P30 CA016672] NR 25 TC 23 Z9 24 U1 1 U2 16 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 PY 2014 VL 13 IS 1 SI SI BP 41 EP 54 PG 14 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA AA3NW UT WOS:000331000400005 PM 23913901 ER PT J AU Kleensang, A Maertens, A Rosenberg, M Fitzpatrick, S Lamb, J Auerbach, S Brennan, R Crofton, KM Gordon, B Fornace, AJ Gaido, K Gerhold, D Haw, R Henney, A Ma'ayan, A McBride, M Monti, S Ochs, MF Pandey, A Sharan, R Stierum, R Tugendreich, S Willett, C Wittwehr, C Xia, JG Patton, GW Arvidson, K Bouhifd, M Hogberg, HT Luechtefeld, T Smirnova, L Zhao, L Adeleye, Y Kanehisa, M Carmichael, P Andersen, ME Hartung, T AF Kleensang, Andre Maertens, Alexandra Rosenberg, Michael Fitzpatrick, Suzanne Lamb, Justin Auerbach, Scott Brennan, Richard Crofton, Kevin M. Gordon, Ben Fornace, Albert J., Jr. Gaido, Kevin Gerhold, David Haw, Robin Henney, Adrian Ma'ayan, Avi McBride, Mary Monti, Stefano Ochs, Michael F. Pandey, Akhilesh Sharan, Roded Stierum, Rob Tugendreich, Stuart Willett, Catherine Wittwehr, Clemens Xia, Jianguo Patton, Geoffrey W. Arvidson, Kirk Bouhifd, Mounir Hogberg, Helena T. Luechtefeld, Thomas Smirnova, Lena Zhao, Liang Adeleye, Yeyejide Kanehisa, Minoru Carmichael, Paul Andersen, Melvin E. Hartung, Thomas TI Pathways of Toxicity SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION LA English DT Article DE systems toxicology; pathways of toxicity; adverse outcome pathways; in vitro toxicology; human toxome ID BIOLOGICAL NETWORKS; SYSTEMS TOXICOLOGY; 21ST-CENTURY; THOUGHT; FOOD; VALIDATION; TOXICOGENOMICS; PERSPECTIVES; TECHNOLOGIES; INTEGRATION AB Despite wide-spread consensus on the need to transform toxicology and risk assessment in order to keep pace with technological and computational changes that have revolutionized the life sciences, there remains much work to be done to achieve the vision of toxicology based on a mechanistic foundation. A workshop was organized to explore one key aspect of this transformation the development of Pathways of Toxicity (PoT) as a key tool for hazard identification based on systems biology. Several issues were discussed in depth in the workshop: The first was the challenge of formally defining the concept of a PoT as distinct from, but complementary to, other toxicological pathway concepts such as mode of action (MoA). The workshop came up with a preliminary definition of PoT as "A molecular definition of cellular processes shown to mediate adverse outcomes of toxicants". It is further recognized that normal physiological pathways exist that maintain homeostasis and these, sufficiently perturbed, can become PoT. Second, the workshop sought to define the adequate public and commercial resources for PoT information, including data, visualization, analyses, tools, and use-cases, as well as the kinds of efforts that will be necessary to enable the creation of such a resource. Third, the workshop explored ways in which systems biology approaches could inform pathway annotation, and which resources are needed and available that can provide relevant PoT information to the diverse user communities. C1 [Kleensang, Andre; Maertens, Alexandra; Bouhifd, Mounir; Hogberg, Helena T.; Luechtefeld, Thomas; Smirnova, Lena; Zhao, Liang; Hartung, Thomas] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Ctr Alternat Anim Testing, Baltimore, MD USA. [Rosenberg, Michael; McBride, Mary] Agilent Technol, Santa Clara, CA USA. [Fitzpatrick, Suzanne; Gaido, Kevin] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Lamb, Justin] Genometry Inc, Cambridge, MA USA. [Auerbach, Scott] NIEHS, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. [Brennan, Richard] Thomson Reuters Inc, Carlsbad, CA USA. [Crofton, Kevin M.] US EPA, Off Res & Dev, Natl Ctr Computat Toxicol, Res Triangle Pk, NC 27711 USA. [Gordon, Ben] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Fornace, Albert J., Jr.] Georgetown Univ, Dept Biochem & Mol & Cellular Biol, Washington, DC USA. [Fornace, Albert J., Jr.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Gerhold, David] NIH, Natl Ctr Adv Translat Sci, Rockville, MD USA. [Haw, Robin] Ontario Inst Canc Res, Reactome, Toronto, ON, Canada. [Henney, Adrian] Heidelberg Univ, German Virtual Liver Network, Heidelberg, Germany. [Ma'ayan, Avi] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY USA. [Monti, Stefano] Boston Univ, Sch Med, Sect Computat Biomed, Boston, MA 02118 USA. [Ochs, Michael F.] Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21205 USA. [Pandey, Akhilesh] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA. [Pandey, Akhilesh] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA. [Pandey, Akhilesh] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Pandey, Akhilesh] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Sharan, Roded] Tel Aviv Univ, Blavatnik Sch Comp Sci, IL-69978 Tel Aviv, Israel. [Stierum, Rob] TNO Hlth Living Microbiol & Syst Biol, Zeist, Netherlands. [Tugendreich, Stuart] Ingenu Syst Inc, Redwood City, CA USA. [Willett, Catherine] Humane Soc United States, Washington, DC USA. [Wittwehr, Clemens] Commiss European Communities, Joint Res Ctr, Syst Toxicol Unit, I-21020 Ispra, Italy. [Xia, Jianguo] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V5Z 1M9, Canada. [Patton, Geoffrey W.; Arvidson, Kirk] US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, College Pk, MD USA. [Adeleye, Yeyejide; Carmichael, Paul] Unilever, Safety & Environm Assurance Ctr, Sharnbrook, Beds, England. [Kanehisa, Minoru] Kyoto Univ, Inst Chem Res, Kyoto 606, Japan. [Andersen, Melvin E.] Hamner Inst Hlth Sci, Res Triangle Pk, NC 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,W7032, Baltimore, MD 21205 USA. EM thartung@jhsph.edu RI Crofton, Kevin/J-4798-2015; Zhao, Liang/I-4777-2015; OI Crofton, Kevin/0000-0003-1749-9971; Zhao, Liang/0000-0002-2126-6778; Kleensang, Andre/0000-0002-4564-7399 FU Unilever; NIH transformative research project on "Mapping the Human Toxome by Systems Toxicology" [R01ES020750]; FDA grant "DNTox-21c Identification of pathways of developmental neurotoxicity for high throughput testing by metabolomics" [U01FD004230] FX This CAAT workshop on Pathways of Toxicity was made possible by support from Unilever and the extensive discussions and experiences of the NIH transformative research project on "Mapping the Human Toxome by Systems Toxicology" (R01ES020750) and FDA grant "DNTox-21c Identification of pathways of developmental neurotoxicity for high throughput testing by metabolomics" (U01FD004230). NR 58 TC 38 Z9 39 U1 1 U2 14 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 2014 VL 31 IS 1 BP 53 EP 61 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 304MF UT WOS:000330750300007 PM 24127042 ER PT J AU Bale, AS Kenyon, E Flynn, TJ Lipscomb, JC Mendrick, DL Hartung, T Patton, GW AF Bale, Ambuja S. Kenyon, Elaina Flynn, Thomas J. Lipscomb, John C. Mendrick, Donna L. Hartung, Thomas Patton, Geoffrey W. TI Correlating In Vitro Data to In Vivo Findings for Risk Assessment SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION LA English DT Editorial Material DE risk assessment; in vitro-to-in vivo correlation; biomarkers; toxome ID HUMAN MICROSOMAL PROTEIN; METABOLIC-CLEARANCE; HEPATIC MICROSOMES; SCALING FACTORS; LIVER; MODELS; EXTRAPOLATION; FOOD; HEPATOTOXICITY; TOXICOLOGY AB A special session at the Toxicology and Risk Assessment Conference in Cincinnati, OH, USA in May, 2012 presented approaches to expand current uses of in vitro toxicity data for risk assessment. Evaluation of xenobiotics through use of in vitro study methods is increasing exponentially and these methodologies offer a relatively fast and considerably cheaper way to determine toxicities in comparison to traditional animal-based approaches. One of the challenges with in vitro data is to effectively use this information for risk assessment purposes. Currently, in vitro studies are used as supportive information for hazard characterization and to identify mechanisms associated with toxicity. Being able to effectively correlate in vitro effects with in vivo observations represents a major challenge for risk assessors. The presentations in this special session provided innovative approaches toward effectively using in vitro data for the human health risk assessment process C1 [Bale, Ambuja S.] US EPA, Off Res & Dev, Natl Ctr Environm Assessment, Washington, DC 20460 USA. [Kenyon, Elaina] US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. [Flynn, Thomas J.] US FDA, Neurotoxicol & In Vitro Toxicol Branch, Div Toxicol, Off Appl Res & Safety Assessment,Ctr Food Safety, Laurel, MD USA. [Lipscomb, John C.] US EPA, Natl Ctr Environm Assessment, Cincinnati, OH 45268 USA. [Mendrick, Donna L.] US FDA, Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA. [Hartung, Thomas] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, CAAT, Baltimore, MD USA. [Hartung, Thomas] Univ Konstanz, CAAT Europe, Constance, Germany. [Patton, Geoffrey W.] US FDA, Div Food Contact Notificat, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Bale, AS (reprint author), US EPA, Off Res & Dev, Natl Ctr Environm Assessment, 1200 Penn Ave NW, Washington, DC 20460 USA. EM ambujabale@gmail.com NR 34 TC 2 Z9 2 U1 0 U2 4 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 2014 VL 31 IS 1 BP 79 EP 90 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 304MF UT WOS:000330750300009 PM 24248035 ER PT J AU Calvo, MS Moshfegh, AJ Tucker, KL AF Calvo, Mona S. Moshfegh, Alanna J. Tucker, Katherine L. TI Assessing the Health Impact of Phosphorus in the Food Supply: Issues and Considerations SO ADVANCES IN NUTRITION LA English DT Article ID SERUM PARATHYROID-HORMONE; CHRONIC KIDNEY-DISEASE; CARDIOVASCULAR-DISEASE; HEMODIALYSIS-PATIENTS; CALCIUM HOMEOSTASIS; PHOSPHATE ADDITIVES; DIETARY PHOSPHORUS; MINERAL METABOLISM; NUTRIENT DATABASES; MORTALITY RISK AB The Western dietary pattern of intake common to many Americans is high in fat, refined carbohydrates, sodium, and phosphorus, all of which are associated with processed food consumption and higher risk of life-threatening chronic diseases. In this review, we focus on the available information on current phosphorus intake with this Western dietary pattern, and new knowledge of how the disruption of phosphorus homeostasis can occur when intake of phosphorus far exceeds nutrient needs and calcium intake is limited. Elevation of extracellular phosphorus, even when phosphorus intake is seemingly modest, but excessive relative to need and calcium intake, may disrupt the endocrine regulation of phosphorus balance in healthy individuals, as it is known to do in renal disease. This elevation in serum phosphate, whether episodic or chronically sustained, may trigger the secretion of regulatory hormones, whose actions can damage tissue, leading to the development of cardiovascular disease, renal impairment, and bone loss. Therefore, we assessed the health impact of excess phosphorus intake in the context of specific issues that reflect changes over time in the U.S. food supply and patterns of intake. Important issues include food processing and food preferences, the need to evaluate phosphorus intake in relation to calcium intake and phosphorus bioavailability, the accuracy of various approaches used to assess phosphorus intake, and the difficulties encountered in evaluating the relations of phosphorus intake to chronic disease markers or incident disease. C1 [Calvo, Mona S.] US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Moshfegh, Alanna J.] ARS, Food Surveys Res Grp, USDA, Beltsville, MD USA. [Tucker, Katherine L.] Univ Massachusetts Lowell, Dept Clin Lab & Nutr Sci, Lowell, MA USA. RP Calvo, MS (reprint author), US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. FU American Society for Nutrition; American Society for Nephrology FX Presented at the symposium "Dietary Phosphorus Excess: A Risk Factor in Chronic Bone, Kidney, and Cardiovascular Disease" held at the 2013 American Society for Nutrition Scientific Sessions and Annual Meeting at Experimental Biology, 24 April 2013 in Boston, MA. The symposium was sponsored by the American Society for Nutrition and supported in part by the American Society for Nephrology. A summary of this was published in the September 2013 issue of Advances in Nutrition. NR 49 TC 14 Z9 14 U1 3 U2 34 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 2161-8313 EI 2156-5376 J9 ADV NUTR JI Adv. Nutr. PD JAN PY 2014 VL 5 IS 1 BP 104 EP 113 DI 10.3945/an.113004861 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 301UP UT WOS:000330557900016 PM 24425729 ER PT J AU Alvandi, F Kwitkowski, VE Ko, CW Rothmann, MD Ricci, S Saber, H Ghosh, D Brown, J Pfeiler, E Chikhale, E Grillo, J Bullock, J Kane, R Kaminskas, E Farrell, AT Pazdur, R AF Alvandi, Firoozeh Kwitkowski, Virginia E. Ko, Chia-Wen Rothmann, Mark D. Ricci, Stacey Saber, Haleh Ghosh, Debasis Brown, Janice Pfeiler, Erika Chikhale, Elsbeth Grillo, Joseph Bullock, Julie Kane, Robert Kaminskas, Edvardas Farrell, Ann T. Pazdur, Richard TI US Food and Drug Administration Approval Summary: Omacetaxine Mepesuccinate as Treatment for Chronic Myeloid Leukemia SO ONCOLOGIST LA English DT Article DE FDA; Omacetaxine mepesuccinate; CML; Chronic myeloid leukemia AB On October 26, 2012, the U.S. Food and Drug Administration (FDA) granted accelerated approval to omacetaxine mepesuccinate (Synribo; Teva Pharmaceuticals USA, Inc., North Wales, PA, http:// www. tevausa. com) for the treatment of adult patients with chronic phase (CP) or accelerated phase (AP) chronic myeloid leukemia (CML) with resistance and/ or intolerance to two or more tyrosine kinase inhibitors (TKIs). The approvalwas basedontheFDAreviewofdata from111 patients withCML inCPor inAPwhohadreceivedtwoormorepriorTKIs, including imatinib. Major cytogenetic responsewas achieved in 18% ofpatientswithCP, withamedianresponsedurationof12.5 months. Major hematologic response was achieved in 14% of patients with AP, with a median response duration of 4.7 months. TheFDAsafetyevaluationwasbasedonsubmitteddata from 163 patients with CP or AP CML who had received at least one dose of omacetaxine mepesuccinate. The safety evaluationwas limited by the single-arm design of the clinical trials as conducted in a small number of previously treated patients. The mostcommon ($ 20%) adverse reactions of any grade in enrolled patients included thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, and infection. The FDA concluded that omacetaxine mepesuccinate has shown activity and a favorable benefit-to-risk profile for the studied population of adult patients with CML (CP or AP) with resistance and/ or intolerance to two or more TKIs. Further evidence of response durability to verify clinical benefit is pending. C1 [Alvandi, Firoozeh; Kwitkowski, Virginia E.; Ricci, Stacey; Saber, Haleh; Kane, Robert; Kaminskas, Edvardas; Farrell, Ann T.; Pazdur, Richard] US FDA, Off Hematol & Oncol Prod, Off New Drugs, Silver Spring, MD 20993 USA. [Ko, Chia-Wen; Rothmann, Mark D.] US FDA, Off Biostat, Silver Spring, MD 20993 USA. [Ghosh, Debasis; Brown, Janice; Pfeiler, Erika; Chikhale, Elsbeth] US FDA, Off Pharmaceut Sci, Silver Spring, MD 20993 USA. [Grillo, Joseph; Bullock, Julie] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Kwitkowski, VE (reprint author), US FDA, Div Hematol Prod, 10903 New Hampshire Ave,Room 2161, Silver Spring, MD 20993 USA. EM virginia.kwitkowski@fda.hhs.gov NR 5 TC 12 Z9 13 U1 0 U2 4 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JAN PY 2014 VL 19 IS 1 BP 94 EP 99 DI 10.1634/theoncologist.2013-0077 PG 6 WC Oncology SC Oncology GA 297YP UT WOS:000330291300013 PM 24309980 ER PT J AU McClenahan, SD Uhlenhaut, C Krause, PR AF McClenahan, Shasta D. Uhlenhaut, Christine Krause, Philip R. TI Optimization of virus detection in cells using massively parallel sequencing SO BIOLOGICALS LA English DT Article DE Virus detection; Massively parallel sequencing (MPS); Non-specific PCR ID PORCINE CIRCOVIRUS; KAPOSIS-SARCOMA; SAMPLES; LINES; IDENTIFICATION; PARVOVIRUS; CHILDREN; DISEASES; ASSAY; SV40 AB Massively parallel sequencing (MPS)-based virus detection has potential regulatory applications. We studied the ability of one of these approaches, based on degenerate oligonucleotide primer (DOP)-polymerase chain reaction (PCR), to detect viral sequences in cell lines known to express viral genes or particles. DOP-PCR was highly sensitive for the detection of small quantities of isolated viral sequences. Detected viral sequences included nodavirus, bracovirus, and endogenous retroviruses in High Five cells, porcine circovirus type 1 and porcine endogenous retrovirus in P1(15 cells, human T-cell leukemia virus 1 in M.) cells, human papillomavirus 18 in HeLa cells, human herpesvirus 8 in BCBL-1 cells, and Epstein Barr Virus in Raji cells. Illumina sequencing (for which primers were most efficiently added using PCR) provided greater sensitivity for virus detection than Roche 454 sequencing. Analyzing nucleic acids extracted both directly from samples and from capsid-enriched preparations provided useful information. Although there are limitations of these methods, these results indicate significant promise for the combination of nonspecific PCR and MPS in identifying contaminants in clinical and biological samples, including cell lines and reagents used to produce vaccines and therapeutic products. (C) 2013 Published by Elsevier Ltd on behalf of The International Alliance for Biological Standardization. C1 [McClenahan, Shasta D.; Krause, Philip R.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Uhlenhaut, Christine] Robert Koch Inst, Ctr Biol Threats & Special Pathogens, Highly Pathogen Viruses ZBS1, D-13353 Berlin, Germany. RP Krause, PR (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM philip.krause@fda.hhs.gov OI Krause, Philip/0000-0002-1045-7536 NR 38 TC 7 Z9 7 U1 0 U2 8 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 EI 1095-8320 J9 BIOLOGICALS JI Biologicals PD JAN PY 2014 VL 42 IS 1 BP 34 EP 41 DI 10.1016/j.biologicals.2013.11.002 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 298OS UT WOS:000330334500005 PM 24309095 ER PT J AU Komatsu, TE Pikis, A Naeger, LK Harrington, PR AF Komatsu, Takashi E. Pikis, Andreas Naeger, Lisa K. Harrington, Patrick R. TI Resistance of human cytomegalovirus to ganciclovir/valganciclovir: A comprehensive review of putative resistance pathways SO ANTIVIRAL RESEARCH LA English DT Review DE Cytomegalovirus; Ganciclovir; Valganciclovir; Resistance; Cidofovir; Foscarnet ID DNA-POLYMERASE MUTATIONS; ORGAN TRANSPLANT RECIPIENTS; STEM-CELL TRANSPLANTATION; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; OPEN READING FRAME; ANTICYTOMEGALOVIRUS COMPOUND AIC246; CONFERRING FOSCARNET RESISTANCE; PLAQUE REDUCTION ASSAY; GANCICLOVIR-RESISTANT; DRUG-RESISTANCE AB Human cytomegalovirus (HCMV) is a pathogen that can be life-threatening in immunocompromised individuals. Valganciclovir and its parent drug ganciclovir are currently the principle drugs used for the treatment or prevention of HCMV disease. The development of HCMV resistance to ganciclovir/valganciclovir has been documented in treated patients and is associated with the emergence of amino acid substitutions in the viral proteins pUL97, pUL54 or both. Generally, single amino acid substitutions associated with clinical resistance that alone do not confer decreased ganciclovir susceptibility in cell culture have been disregarded as causative or clinically significant. This review focuses on the analysis and mechanisms of antiviral drug resistance to HCMV. We also conducted a review of publicly available clinical and nonclinical data to construct a comprehensive list of pUL97 and pUL54 amino acid substitutions that are associated with a poor clinical response to the first line therapies ganciclovir and valganciclovir, or associated with reduced HCMV ganciclovir susceptibility in cell culture. Over 40 putative ganciclovir/valganciclovir resistance-associated substitutions were identified in this analysis. These include the commonly reported substitutions M460I/V and C592G in pUL97. There were additional substitutions that are not widely considered as ganciclovir/valganciclovir resistance-associated substitutions, including V466M in pUL97 and E315D in pUL54. Some of these ganciclovir/valganciclovir resistance-associated substitutions may confer cross-resistance to other HCMV therapies, such as cidofovir and foscarnet. Based on this review, we propose that there are more potential HCMV ganciclovir/valganciclovir resistance pathways than generally appreciated. The resulting comprehensive list of putative ganciclovir/valganciclovir resistance-associated substitutions provides a foundation for future investigations to characterize the role of specific substitutions or combinations of substitutions, which will enhance our understanding of HCMV mechanisms of ganciclovir/valganciclovir resistance and also provide insight regarding the potential for cross-resistance to other HCMV therapies. Published by Elsevier B.V. C1 [Komatsu, Takashi E.; Pikis, Andreas; Naeger, Lisa K.; Harrington, Patrick R.] US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Pikis, Andreas] NIDCR, Microbial Biochem & Genet Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Komatsu, TE (reprint author), US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22 Room 6323, Silver Spring, MD 20993 USA. EM Takashi.Komatsu@fda.hhs.gov FU Intramural Research Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland FX We thank Debra Birnkrant, Mike Bray, Edward Cox, Jeffrey Murray, Jules O'Rear, and Kuate Seraphin for helpful manuscript suggestions and discussion. A.P. is supported in part by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland. NR 191 TC 21 Z9 23 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 EI 1872-9096 J9 ANTIVIR RES JI Antiviral Res. PD JAN PY 2014 VL 101 BP 12 EP 25 DI 10.1016/j.antiviral.2013.10.011 PG 14 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 290QF UT WOS:000329772700002 PM 24184129 ER PT J AU Dreher, ML Nagaraja, S Bui, H Hong, D AF Dreher, Maureen L. Nagaraja, Srinidhi Bui, Hieu Hong, Danny TI Characterization of load dependent creep behavior in medically relevant absorbable polymers SO JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS LA English DT Article DE Creep; Absorbable; PLLA; PLGA; Crystallinity; Viscoelasticity ID IN-VITRO DEGRADATION; MECHANICAL-PROPERTIES; BIODEGRADABLE POLYMERS; POLY(L-LACTIC ACID); FAILURE; FIXATION; POLYLACTIDES; SCAFFOLDS; DEVICES; FORCES AB While synthetic absorbable polymers have a substantial history of use in medical devices, their use is expanding and becoming more prevalent for devices where long term loading and structural support is required. In addition, there is evidence that current absorbable medical devices may experience permanent deformations, warping (out of plane twisting), and geometric changes in vivo. For clinical indications with long term loading or structural support requirements, understanding the material's viscoelastic properties becomes increasingly important whereas these properties have not been used historically as preclinical indications of performance or design considerations. In this study we measured the static creep, creep recovery and cyclic creep responses of common medically relevant absorbable materials (i.e., poly(L-lactide, PLLA) and poly(1-co-glycolide, PLGA) over a range of physiologically relevant loading magnitudes. The results indicate that both PLLA and PLGA exhibit creep behavior and failure at loads significantly less than the yield or ultimate properties of the material and that significant material specific responses to loading exist. In addition, we identified a strong correlation between the extent of creep in the material and its crystallinity. Results of the study provide new information on the creep behavior of PLLA and PLGA and support the use of viscoelastic properties of absorbable polymers as part of the material selection process. Published by Elsevier Ltd. C1 [Dreher, Maureen L.; Nagaraja, Srinidhi] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Solid & Fluid Mech, Silver Spring, MD 20993 USA. [Bui, Hieu; Hong, Danny] CDRH Med Device Fellowship Program, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Solid & Fluid Mech, Silver Spring, MD 20993 USA. RP Dreher, ML (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Solid & Fluid Mech, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Maureen.dreher@fda.hhs.gov RI Bui, Hieu/J-4408-2014 OI Bui, Hieu/0000-0002-0038-8266 FU CDRH's Medical Device Fellowship Program; FDA's Office of the Critical Path Initiative FX We gratefully acknowledge FDA's Office of the Critical Path Initiative for funding the study and CDRH's Medical Device Fellowship Program for student funding. We also gratefully acknowledge Dr. Scott Miller for assistance with statistical analyses. NR 39 TC 5 Z9 5 U1 5 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1751-6161 EI 1878-0180 J9 J MECH BEHAV BIOMED JI J. Mech. Behav. Biomed. Mater. PD JAN PY 2014 VL 29 SI SI BP 470 EP 479 DI 10.1016/j.jmbbm.2013.10.005 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 294ZF UT WOS:000330085700043 PM 24211356 ER PT J AU Zhang, L AF Zhang, Lei TI SCIENTIFIC AND REGULATORY PERSPECTIVES ON DRUG INTERACTION EVALUATION DURING DRUG DEVELOPMENT SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 10th International Meeting of the International-Society-for-the-Study-of-Xenobiotics (ISSX) CY SEP 29-OCT 03, 2013 CL Toronto, CANADA SP Int Soc Study Xenobiot C1 [Zhang, Lei] US FDA, Off Clin Pharmacol, Off Translat Sci, CDER, Silver Spring, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0360-2532 EI 1097-9883 J9 DRUG METAB REV JI Drug Metab. Rev. PD JAN PY 2014 VL 45 SU 1 BP 18 EP 18 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 286DO UT WOS:000329445700042 ER PT J AU Mulgaonkar, A Ragueneau-Majlessi, I Chung, S Zhang, L Zhao, P AF Mulgaonkar, Aditi Ragueneau-Majlessi, Isabelle Chung, Sophie Zhang, Lei Zhao, Ping TI ANALYSIS OF METABOLISM AND TRANSPORT DRUG INTERACTION DATA IN 2012 NEW DRUG APPLICATIONS SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 10th International Meeting of the International-Society-for-the-Study-of-Xenobiotics (ISSX) CY SEP 29-OCT 03, 2013 CL Toronto, CANADA SP Int Soc Study Xenobiot C1 [Mulgaonkar, Aditi; Ragueneau-Majlessi, Isabelle; Chung, Sophie] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA. [Zhang, Lei] US FDA, Off Clin Pharmacol, Off Translat Sci, CDER, Silver Spring, MD USA. [Zhao, Ping] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0360-2532 EI 1097-9883 J9 DRUG METAB REV JI Drug Metab. Rev. PD JAN PY 2014 VL 45 SU 1 BP 117 EP 118 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 286DO UT WOS:000329445700237 ER PT J AU Chaudhry, AS Yang, X Lee, SJ Burckart, GJ Fan, YP Guengerich, FP Strom, SC Thummel, K Schuetz, EG AF Chaudhry, Amarjit S. Yang, Xia Lee, Su-Jun Burckart, Gilbert J. Fan, Yiping Guengerich, F. Peter Strom, Stephen C. Thummel, Kenneth Schuetz, Erin G. TI FUNCTIONAL SIGNIFICANCE OF SNPS ON CYP3A4 EXPRESSION AND ACTIVITY IN CAUCASIAN LIVERS SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 10th International Meeting of the International-Society-for-the-Study-of-Xenobiotics (ISSX) CY SEP 29-OCT 03, 2013 CL Toronto, CANADA SP Int Soc Study Xenobiot C1 [Chaudhry, Amarjit S.; Schuetz, Erin G.] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA. [Yang, Xia] Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA USA. [Lee, Su-Jun] Inje Univ, Coll Med, Dept Pharmacol, Pusan, South Korea. [Lee, Su-Jun] Inje Univ, Coll Med, PharmacoGen Res Ctr, Pusan, South Korea. [Burckart, Gilbert J.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. [Fan, Yiping] St Jude Childrens Res Hosp, Dept Computat Biol, Memphis, TN 38105 USA. [Guengerich, F. Peter] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37212 USA. [Strom, Stephen C.] Karolinska Hosp & Inst, Dept Lab Med, Stockholm, Sweden. [Thummel, Kenneth] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0360-2532 EI 1097-9883 J9 DRUG METAB REV JI Drug Metab. Rev. PD JAN PY 2014 VL 45 SU 1 BP 214 EP 214 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 286DO UT WOS:000329445700429 ER PT J AU Warren, M Jahic, M Huang, J Shi, Q Salminen, W Huang, Y AF Warren, Mark Jahic, Mirza Huang, Jane Shi, Qiang Salminen, William Huang, Yong TI TRANSPORTER INHIBITION BY HERBAL SUPPLEMENTS - POTENTIAL DRUG-DIETARY SUPPLEMENT INTERACTIONS SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 10th International Meeting of the International-Society-for-the-Study-of-Xenobiotics (ISSX) CY SEP 29-OCT 03, 2013 CL Toronto, CANADA SP Int Soc Study Xenobiot C1 [Warren, Mark; Jahic, Mirza; Huang, Jane; Huang, Yong] Optivia Biotechnol Inc, Menlo Pk, CA USA. [Shi, Qiang] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Salminen, William] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0360-2532 EI 1097-9883 J9 DRUG METAB REV JI Drug Metab. Rev. PD JAN PY 2014 VL 45 SU 1 BP 256 EP 256 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 286DO UT WOS:000329445700511 ER PT J AU Dal Pan, G AF Dal Pan, Gerald J. TI Ongoing Challenges in Pharmacovigilance SO DRUG SAFETY LA English DT Article ID ADVERSE DRUG-REACTIONS; APPROVED MEDICATION GUIDES; HEALTH-CARE UTILIZATION; EVENT REPORTING SYSTEM; SIGNAL-DETECTION; CONTAMINATED HEPARIN; OFF-LABEL; SAFETY; FDA; INFORMATION AB While pharmacovigilance systems have made substantial progress in the past several decades, all pharmacovigilance systems face a common set of ongoing challenges in drug safety surveillance in five principal interrelated areas: engaging the public, collaboration and partnerships, incorporating informatics, adopting a global approach, and assessing the impact of efforts. In broad terms, these challenges are not new. Rather, advances in science and technology, along with more demanding societal expectations, have changed the nature of these challenges and provided new opportunities to move the field forward. Differences in organization and levels of development, as well as regional differences, necessarily imply that a single approach is not suitable for all regions, though sharing of best practices can help each region. C1 US FDA, Silver Spring, MD 20993 USA. RP Dal Pan, G (reprint author), US FDA, 10903 New Hampshire Ave,Bldg 22,Room 4304, Silver Spring, MD 20993 USA. EM gerald.dalpan@fda.hhs.gov NR 75 TC 6 Z9 6 U1 1 U2 4 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 EI 1179-1942 J9 DRUG SAFETY JI Drug Saf. PD JAN PY 2014 VL 37 IS 1 BP 1 EP 8 DI 10.1007/s40264-013-0123-x PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 288PT UT WOS:000329624800001 PM 24264884 ER PT J AU Partyka, ML Bond, RF Farrar, J Falco, A Cassens, B Cruse, A Atwill, ER AF Partyka, Melissa L. Bond, Ronald F. Farrar, Jeff Falco, Andy Cassens, Barbara Cruse, Alonza Atwill, Edward R. TI Quantifying the Sensitivity of Scent Detection Dogs To Identify Fecal Contamination on Raw Produce SO JOURNAL OF FOOD PROTECTION LA English DT Article ID OLFACTORY DETECTION; CRYPTOSPORIDIUM-PARVUM; CANIS-FAMILIARIS; FRESH PRODUCE; OUTBREAKS; ACCURACY; IDENTIFICATION; CALIFORNIA; PRINCIPLE; DIAGNOSIS AB Consumption of raw produce commodities has been associated with foodborne outbreaks in the United States. In a recent Centers for Disease Control and Prevention report outlining the incidence of food-related outbreaks from 1998 to 2008, produce of all kinds were implicated in 46% of illnesses and 23% of deaths. Methods that quickly identify fecal contamination of foods, including produce, will allow prioritization of samples for testing during investigations and perhaps decrease the time required to identify specific brands or lots. We conducted a series of trials to characterize the sensitivity and specificity of scent detection dogs to accurately identify fecal contamination on raw agricultural commodities (romaine lettuce, spinach, cilantro, and roma tomatoes). Both indirect and direct methods of detection were evaluated. For the indirect detection method, two dogs were trained to detect contamination on gauze pads previously exposed to produce contaminated with feces. For the direct detection method, two dogs were trained to identify fecal contamination on fresh produce. The indirect method did not result in acceptable levels of sensitivity except for the highest levels of fecal contamination (25 g of feces). Each dog had more difficulty detecting fecal contamination on cilantro and spinach than on roma tomatoes. For the direct detection method, the dogs exhibited >75% sensitivity for detecting >= 0.25 g of feces on leafy greens (cilantro, romaine lettuce, and spinach) and roma tomatoes, with sensitivity declining as the amount of feces dropped below 0.025 g. We determined that use of a scent detection dog to screen samples for testing can increase the probability of detecting >= 0.025 g of fecal contamination by 500 to 3,000% when samples with fecal contamination are rare (<= 1%) C1 [Partyka, Melissa L.; Bond, Ronald F.; Atwill, Edward R.] Univ Calif Davis, Sch Vet Med, Western Inst Food Safety & Secur, Davis, CA 95616 USA. [Farrar, Jeff] US FDA, Off Food & Vet Med, Silver Spring, MD 20993 USA. [Falco, Andy] Falco K9 Acad, Brea, CA 92821 USA. [Cassens, Barbara] US FDA, Off Partnerships, Rockville, MD 20857 USA. [Cruse, Alonza] US FDA, Off Regulatory Affairs, Los Angeles Dist Off, Irvine, CA 92620 USA. RP Atwill, ER (reprint author), Univ Calif Davis, Sch Vet Med, Western Inst Food Safety & Secur, 1089 Vet Med Dr, Davis, CA 95616 USA. EM ratwill@ucdavis.edu FU California Department of Food and Agriculture, Specialty Crop Block Grant Program; U.S. Food and Drug Administration [U01-003-572] FX The authors extend our appreciation to Andrew Gordus (California Department of Fish and Wildlife) and Thomas McCoy (T.J. McCoy and Associates, Kansas City, MO) for their invaluable assistance. The authors also thank Dr. Lisa Lit (Department of Animal Sciences, University of California, Davis) for her valuable feedback and advice and Dr. Brenda McCowan (Population Health and Reproduction, University of California, Davis) for continual support and guidance. This work was funded by a grant from the California Department of Food and Agriculture, Specialty Crop Block Grant Program, with additional funding from the U.S. Food and Drug Administration (project U01-003-572). NR 36 TC 2 Z9 2 U1 0 U2 15 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 2014 VL 77 IS 1 BP 6 EP 14 DI 10.4315/0362-028X.JFP-13-249 PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 288DX UT WOS:000329593300001 PM 24405993 ER PT J AU Li, HP Fu, XW Bima, YG Koontz, J Megalis, C Yang, F Fleischman, G Tortorello, ML AF Li, Haiping Fu, Xiaowen Bima, Yige Koontz, John Megalis, Christina Yang, Fei Fleischman, Gregory Tortorello, Mary Lou TI Effect of the Local Microenvironment on Survival and Thermal Inactivation of Salmonella in Low- and Intermediate-Moisture Multi-Ingredient Foods SO JOURNAL OF FOOD PROTECTION LA English DT Article ID PEANUT BUTTER; INTERNATIONAL OUTBREAK; CONTAMINATED CHOCOLATE; TYPHIMURIUM; ORANIENBURG; EASTBOURNE; RESISTANCE AB Multi-ingredient foods having low- or intermediate-moisture characteristics may pose a special challenge to process design and validation. Ingredients of these foods can create local microenvironments that may have a distinct impact on pathogen survival and processing requirements. In this study, two model systems, each consisting of 80% commercial peanut butter (P) and 20% nonfat dry milk powder (M), were formulated to be identical in composition, but different in the source of the Salmonella contamination as originating in either the ingredient P or M. Immediately after inoculation, Salmonella showed a 2.0-log reduction when M was the contaminated ingredient compared with a 0.6-log reduction when P was the contaminated ingredient. This pattern of survival was consistent with the single-ingredient control containing only M (2.5-log reduction) or only P (0.7-log reduction), suggesting that the immediate proximity of cells is determined by the contaminated ingredient in the model system. After 5 weeks of storage, the survival rates of Salmonella in the two systems remained different, i.e. a 4- and 2-log reduction resulted in the system with M or P as the contaminated ingredient, respectively. Furthermore, thermal inactivation efficacies also differed significantly between the two systems. Fourier transform infrared spectroscopy demonstrated the nonhomogeneous distribution of water, lipid, and protein, indicating that varied local microenvironments were present and likely affected the behavior of the pathogen. The impact of the microenvironment on inactivation and survival of Salmonella was further confirmed in a butter cookie formulation in which Salmonella was inoculated via four different ingredients. This study shows that the local microenvironment in low- and intermediate-moisture foods affects Salmonella survival and thermal inactivation. The ingredient source of the contamination should be taken into account for process design and validation to ensure the safety of the product. C1 [Li, Haiping; Koontz, John; Megalis, Christina; Fleischman, Gregory; Tortorello, Mary Lou] US FDA, Div Food Proc Sci & Technol, Bedford Pk, IL 60501 USA. [Fu, Xiaowen; Bima, Yige; Yang, Fei] IIT, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. RP Li, HP (reprint author), US FDA, Div Food Proc Sci & Technol, 6502 South Archer Rd, Bedford Pk, IL 60501 USA. EM haiping.li@fda.hhs.gov FU U.S. Food and Drug Administration FX The authors are very grateful for the insightful critical reviews provided by Jenny Scott and John Larkin. This work was supported in part by a grant from the U.S. Food and Drug Administration to the Institute for Food Safety and Health, Illinois Institute of Technology. NR 20 TC 8 Z9 8 U1 0 U2 40 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 2014 VL 77 IS 1 BP 67 EP 74 DI 10.4315/0362-028X.JFP-13-277 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 288DX UT WOS:000329593300008 PM 24406000 ER PT J AU Holzgrefe, H Ferber, G Champeroux, P Gill, M Honda, M Greiter-Wilke, A Baird, T Meyer, O Saulnier, M AF Holzgrefe, Henry Ferber, Georg Champeroux, Pascal Gill, Michael Honda, Masaki Greiter-Wilke, Andrea Baird, Theodore Meyer, Olivier Saulnier, Muriel TI Preclinical QT safety assessment: Cross-species comparisons and human translation from an industry consortium SO JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS LA English DT Article DE Biomarker; Cynomolgus monkey; Dog; Guinea pig; Marmoset; Methods; Minipig; Moxifloxacin; Preclinical-clinical concordance; QT rate-correction ID HEART-RATE CORRECTION; GUINEA-PIG HEART; TORSADES-DE-POINTES; TELEMETERED CYNOMOLGUS MONKEYS; MARMOSETS CALLITHRIX-JACCHUS; I-KR BLOCKADE; INTERVAL PROLONGATION; COMMON MARMOSETS; BEAGLE DOGS; CONSCIOUS DOG AB Introduction: In vivo models have been required to demonstrate relative cardiac safety, but model sensitivity has not been systematically investigated. Cross-species and human translation of repolarization delay, assessed as QT/QTc prolongation, has not been compared employing common methodologies across multiple species and sites. Therefore, the accurate translation of repolarization results within and between preclinical species, and to man, remains problematic. Methods: Six pharmaceutical companies entered into an informal consortium designed to collect high-resolution telemetered data in multiple species (dog; n = 34, cynomolgus; n = 37, minipig; n = 12, marmoset; n = 14, guinea pig; n = 5, and man; n = 57). All animals received vehicle and varying doses of moxifloxacin (3-100 mg/kg, p.o.) with telemetered ECGs (>= 500 Hz) obtained for 20-24 h post-dose. Individual probabilistic QT-RR relationships were derived for each subject. The rate-correction efficacies of the individual (QTca) and generic correction formulae (Bazett, Fridericia, and Van de Water) were objectively assessed as the mean squared slopes of the QTc-RR relationships. Normalized moxifloxacin QTca responses (Veh Delta%/mu M) were derived for 1 h centered on the moxifloxacin Tmax. Results: All QT-RR ranges demonstrated probabilistic uncertainty; slopes varied distinctly by species where dog and human exhibited the lowest QT rate-dependence, which was much steeper in the cynomolgus and guinea pig. Incorporating probabilistic uncertainty, the normalized QTca-moxifloxacin responses were similarly conserved across all species, including man. Discussion: The current results provide the first unambiguous evidence that all preclinical in vivo repolarization assays, when accurately modeled and evaluated, yield results that are consistent with the conservation of moxifloxacin-induced QT prolongation across all common preclinical species. Furthermore, these outcomes are directly transferable across all species including man. The consortium results indicate that the implementation of standardized QTc data presentation, QTc reference cycle lengths, and rate-correction coefficients can markedly improve the concordance of preclinical and clinical outcomes in most preclinical species. (C) 2013 Elsevier Inc. All rights reserved. C1 [Gill, Michael] Bristol Myers Squibb Co, Discovery Toxicol, Princeton, NJ 08543 USA. [Champeroux, Pascal] CERB, Ctr Rech Biol, F-18800 Baugy, France. [Holzgrefe, Henry] Charles River Labs, Reno, NV 89511 USA. [Honda, Masaki] Chugai Pharmaceut Co Ltd, Div Res, Gotemba, Shizuoka 4128513, Japan. [Greiter-Wilke, Andrea; Meyer, Olivier] F Hoffmann La Roche Ltd, CH-4070 Basel, Switzerland. [Baird, Theodore] MPI Res Inc, Mattawan, MI 49071 USA. [Saulnier, Muriel] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Ferber, Georg] Stat Georg Ferber GmbH, CH-4125 Riehen, Switzerland. RP Holzgrefe, H (reprint author), Charles River Labs, Dept Toxicol, 6995 Longley Lane, Reno, NV 89511 USA. EM Henry.holzgrefe@crl.com; Statistik.Georg.Ferber@bluewin.ch; pascal.champeroux@cerb.fr; Michael.gill@bms.com; hondamsk@chugai-pharm.co.jp; andrea.greiter-wilke@roche.com; Theodore.Baird@mpiresearch.com; olivier-meyer@hotmail.com; Muriel.saulnier@fda.hhs.gov NR 149 TC 19 Z9 19 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8719 EI 1873-488X J9 J PHARMACOL TOX MET JI J. Pharmacol. Toxicol. Methods PD JAN-FEB PY 2014 VL 69 IS 1 BP 61 EP 101 DI 10.1016/j.vascn.2013.05.004 PG 41 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 291OA UT WOS:000329836800008 PM 23689033 ER PT J AU Viner, K Perella, D Lopez, A Bialek, S Nguyen, M Spells, N Watson, B AF Viner, Kendra Perella, Dana Lopez, Adriana Bialek, Stephanie Nguyen, Michael Spells, Niya Watson, Barbara TI Comparing Active and Passive Varicella Surveillance in Philadelphia, 2005-2010: Recommendations for the Transition to Nationwide Passive Varicella Disease Surveillance SO PUBLIC HEALTH REPORTS LA English DT Article AB Objective. The Philadelphia Department of Public Health (PDPH) conducts active surveillance for varicella in West Philadelphia. For its approximately 300 active surveillance sites, PDPH mandates biweekly reports of varicella (including zero cases) and performs intensive case investigations. Elsewhere in Philadelphia, surveillance sites passively report varicella cases, and abbreviated investigations are conducted. We used active varicella surveillance program data to inform the transition to nationwide passive varicella surveillance. Methods. We compared classification of reported cases, varicella disease incidence, and reporting completeness for active and passive surveillance areas for 2005-2010. We assessed reporting completeness using capture-recapture analysis of 2- to 18-year-old cases reported by schools/daycare centers and health-care providers. Results. From 2005 to 2010, PDPH received 3,280 passive and 969 active surveillance varicella case reports. Most passive surveillance reports were classified as probable cases (18% confirmed, 56% probable, and 26% excluded), whereas nearly all of the active surveillance reports were either confirmed or excluded (36% confirmed, 11% probable, and 53% excluded). Overall incidence rates calculated using confirmed/probable cases were similar in the active and passive surveillance areas. Detection of laboratory-confirmed, breakthrough, and moderate-to-severe cases was equivalent for both surveillance areas. Conclusions. Although active surveillance for varicella results in better classified cases, passive surveillance provides comparable data for monitoring disease trends in breakthrough and moderate-to-severe varicella. To further improve passive surveillance in the two-dose-varicella vaccine era, jurisdictions should consider conducting periodic enhanced surveillance, encouraging laboratory testing, and collecting additional varicella-specific variables for passive surveillance. C1 [Viner, Kendra; Perella, Dana; Spells, Niya; Watson, Barbara] Philadelphia Dept Publ Hlth, Philadelphia, PA 19146 USA. [Lopez, Adriana; Bialek, Stephanie] Ctr Dis Control & Prevent, Atlanta, GA USA. [Nguyen, Michael] US FDA, Rockville, MD 20857 USA. RP Viner, K (reprint author), Philadelphia Dept Publ Hlth, Div Dis Control, 500 S Broad St, Philadelphia, PA 19146 USA. EM kendra.viner@phila.gov NR 15 TC 0 Z9 0 U1 0 U2 0 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 2014 VL 129 IS 1 BP 47 EP 54 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 288BL UT WOS:000329586900007 PM 24381359 ER PT J AU Bird, ST Crentsil, V Temple, R Pinheiro, S Demczar, D Stone, M AF Bird, Steven T. Crentsil, Victor Temple, Robert Pinheiro, Simone Demczar, Dorothy Stone, Marc TI Cardiac Safety Concerns Remain for Citalopram at Dosages Above 40 mg/Day SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID QT INTERVAL C1 [Stone, Marc] US FDA, Div Epidemiol, Off Pharmacovigilance & Epidemiol, Off Surveillance & Epidemiol,Ctr Drug Evaluat & R, Silver Spring, MD 20993 USA. FDA, Div Psychiat Prod, Silver Spring, MD USA. FDA, Off Drug Evaluat 1, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Stone, M (reprint author), US FDA, Div Epidemiol, Off Pharmacovigilance & Epidemiol, Off Surveillance & Epidemiol,Ctr Drug Evaluat & R, Silver Spring, MD 20993 USA. EM marc.stone@fda.hhs.gov NR 10 TC 5 Z9 7 U1 0 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2014 VL 171 IS 1 BP 17 EP 19 DI 10.1176/appi.ajp.2013.13070905 PG 3 WC Psychiatry SC Psychiatry GA 286OO UT WOS:000329478800005 PM 24399423 ER PT J AU Kluetz, PG Pierce, W Maher, VE Zhang, H Tang, SH Song, PF Liu, Q Haber, MT Leutzinger, EE Al-Hakim, A Chen, W Palmby, T Alebachew, E Sridhara, R Ibrahim, A Justice, R Pazdur, R AF Kluetz, Paul G. Pierce, William Maher, V. Ellen Zhang, Hui Tang, Shenghui Song, Pengfei Liu, Qi Haber, Martin T. Leutzinger, Eldon E. Al-Hakim, Ali Chen, Wei Palmby, Todd Alebachew, Elleni Sridhara, Rajeshwari Ibrahim, Amna Justice, Robert Pazdur, Richard TI Radium Ra 223 Dichloride Injection: US Food and Drug Administration Drug Approval Summary SO CLINICAL CANCER RESEARCH LA English DT Article ID METASTATIC PROSTATE-CANCER; INCREASED SURVIVAL; MITOXANTRONE; PREDNISONE; DOCETAXEL; TRIAL; CHEMOTHERAPY; ABIRATERONE AB On May 15, 2013, the U. S. Food and Drug Administration (FDA) approved radium Ra 223 dichloride (Ra-223; Xofigo injection; Bayer HealthCare Pharmaceuticals Inc.) for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases, and no known visceral metastatic disease. The FDA review was based on clinical trial BC1-06, which randomly allocated patients (2: 1) to either Ra-223 plus best standard of care (BSoC) or placebo plus BSoC. The primary endpoint was overall survival (OS) with a key secondary endpoint of time to first symptomatic skeletal event (SSE). A statistically significant improvement in OS was demonstrated [HR, 0.70; 95% confidence interval, 0.55-0.88, P = 0.0019]. At the prespecified interim analysis, the median OS durations were 14.0 and 11.2 months in the Ra-223 and placebo arms, respectively. The improvement in OS was supported by a delay in time to first SSE favoring the Ra-223 arm. The most common (> 10%) adverse reactions in patients receiving Ra-223 were nausea, diarrhea, vomiting, and peripheral edema. The most common (> 10%) hematologic laboratory abnormalities were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia. Ra-223 is the first a-emitting radiotherapeutic and the first radiopharmaceutical to demonstrate an OS advantage in metastatic prostate cancer. (C) 2013 AACR. C1 [Kluetz, Paul G.; Pierce, William; Maher, V. Ellen; Chen, Wei; Palmby, Todd; Alebachew, Elleni; Ibrahim, Amna; Justice, Robert; Pazdur, Richard] US FDA, Off Hematol & Oncol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Zhang, Hui; Tang, Shenghui; Sridhara, Rajeshwari] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Song, Pengfei; Liu, Qi] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Haber, Martin T.; Leutzinger, Eldon E.; Al-Hakim, Ali] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Off New Drug Qual Assessment, Silver Spring, MD 20993 USA. RP Kluetz, PG (reprint author), US FDA, Off Hematol & Oncol Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,2359, Silver Spring, MD 20993 USA. EM Paul.Kluetz@fda.hhs.gov NR 15 TC 22 Z9 27 U1 0 U2 6 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 JAN 1 PY 2014 VL 20 IS 1 BP 9 EP 14 DI 10.1158/1078-0432.CCR-13-2665 PG 6 WC Oncology SC Oncology GA 284GC UT WOS:000329303100003 PM 24190979 ER PT J AU Wear, KA Gammell, PM Maruvada, S Liu, YB Harris, GR AF Wear, Keith A. Gammell, Paul M. Maruvada, Subha Liu, Yunbo Harris, Gerald R. TI Improved Measurement of Acoustic Output Using Complex Deconvolution of Hydrophone Sensitivity SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID TIME-DELAY SPECTROMETRY; FOCUSED ULTRASOUND FIELDS; PHASE CALIBRATION; FREQUENCY-RESPONSE; MODEL; AMPLITUDE; PRESSURE; SENSOR; MHZ AB The traditional method for calculating acoustic pressure amplitude is to divide a hydrophone output voltage measurement by the hydrophone sensitivity at the acoustic working frequency, but this approach neglects frequency dependence of hydrophone sensitivity. Another method is to perform a complex deconvolution between the hydrophone output waveform and the hydrophone impulse response (the inverse Fourier transform of the sensitivity). In this paper, the effects of deconvolution on measurements of peak compressional pressure (p(+)), peak rarefactional pressure (p(-)), and pulse intensity integral (PII) are studied. Time-delay spectrometry (TDS) was used to measure complex sensitivities from 1 to 40 MHz for 8 hydrophones used in medical ultrasound exposimetry. These included polyvinylidene fluoride (PVDF) spot-poled membrane, needle, capsule, and fiber-optic designs. Subsequently, the 8 hydrophones were used to measure a 4-cycle, 3 MHz pressure waveform mimicking a pulsed Doppler waveform. Acoustic parameters were measured for the 8 hydrophones using the traditional approach and deconvolution. Average measurements (across all 8 hydrophones) of acoustic parameters from deconvolved waveforms were 4.8 MPa (p(+)), 2.4 MPa (p(-)), and 0.21 mJ/cm(2) (PII). Compared with the traditional method, deconvolution reduced the coefficient of variation (ratio of standard deviation to mean across all 8 hydrophones) from 29% to 8% (p(+)), 39% to 13% (p(-)), and 58% to 10% (PII). C1 [Wear, Keith A.; Maruvada, Subha; Liu, Yunbo; Harris, Gerald R.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Gammell, Paul M.] Gammell Appl Technol LLC, Exmore, VA USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM keith.wear@fda.hhs.gov NR 29 TC 7 Z9 7 U1 0 U2 24 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0885-3010 EI 1525-8955 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD JAN PY 2014 VL 61 IS 1 BP 62 EP 75 DI 10.1109/TUFFC.2014.2879 PG 14 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 287EA UT WOS:000329522400006 PM 24402896 ER PT J AU Sun, HH Lee, JJ Papadopoulos, EJ Lee, CS Nelson, RM Sachs, HC Rodriguez, WJ Mulberg, AE AF Sun, Haihao Lee, Jessica J. Papadopoulos, Elektra J. Lee, Catherine S. Nelson, Robert M. Sachs, Hari C. Rodriguez, William J. Mulberg, Andrew E. TI Alternate Endpoints and Clinical Outcome Assessments in Pediatric Ulcerative Colitis Registration Trials SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE clinical outcome measure; disease activity index; pediatric specific endpoints; pediatric ulcerative colitis ID ORAL MESALAMINE; PRO INSTRUMENTS; ACTIVITY INDEX; THERAPY; MODERATE; MULTICENTER; INDUCTION; REMISSION; EFFICACY; CHILDREN AB Objectives:Presently, there is no consensus on endpoint measures to assess clinical outcomes for pediatric ulcerative colitis (UC). This study reviewed the endpoints used in the registration trials of approved drugs for pediatric UC.Methods:The primary efficacy endpoints of all registration trials completed from 1950 to 2008 that led to Food and Drug Administration approval for indications in pediatric and adult UC were reviewed.Results:Colazal and Remicade have been approved for pediatric UC indication, and clinical response was used as a primary endpoint in these registration trials. The clinical response in the adult Colazal trials was defined as a reduction of rectal bleeding and improvement in at least one of the other assessed symptoms (stool frequency, patient functional assessment, abdominal pain, sigmoidoscopic grade, and physician's global assessment) assessed by the Sutherland UC Activity Index. The pediatric Colazal trial defined clinical response using the Modified Sutherland UC Activity Index, which excluded abdominal pain and functional assessment. Both adult and pediatric Remicade trials used clinical response defined by the Mayo score as the primary endpoint. The Pediatric Ulcerative Colitis Activity Index was used to measure various secondary endpoints in the pediatric Remicade trial.Conclusions:Pediatric-specific endpoints were used, but outcome measures and definition of clinical response were not consistent in pediatric UC trials. Consensus on the definition of successful treatment outcome (clinical response and/or remission) and collaboration in the development of well-defined and reliable measures of signs and symptoms for use in conjunction with endoscopic parameters of mucosal healing will facilitate pediatric drug development. C1 [Sun, Haihao; Lee, Catherine S.; Nelson, Robert M.; Rodriguez, William J.] US FDA, Off Pediat Therapeut, Off Commissioner, Ctr Drug Res & Evaluat, Silver Spring, MD 20993 USA. [Lee, Jessica J.; Mulberg, Andrew E.] US FDA, Div Gastroenterol & Inborn Errors Prod, Ctr Drug Res & Evaluat, Silver Spring, MD 20993 USA. [Papadopoulos, Elektra J.] US FDA, Study Endpoint & Labeling Dev SEALD, Ctr Drug Res & Evaluat, Silver Spring, MD 20993 USA. [Sachs, Hari C.] US FDA, Pediat & Maternal Hlth Staff, Off New Drug, Ctr Drug Res & Evaluat, Silver Spring, MD 20993 USA. RP Mulberg, AE (reprint author), US FDA, Div Gastroenterol & Inborn Errors Prod, Off New Drug, Ctr Drug Res & Evaluat, 10903 New Hampshire Ave,Bldg 22,Room 5120, Silver Spring, MD 20993 USA. EM Andrew.Mulberg@fda.hhs.gov NR 19 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD JAN PY 2014 VL 58 IS 1 BP 12 EP 17 DI 10.1097/MPG.0000000000000186 PG 6 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 282QR UT WOS:000329188000016 PM 24121142 ER PT J AU Avalos, LA Chen, H Yang, CM Andrade, SE Cooper, WO Cheetham, CT Davis, RL Dublin, S Hammad, TA Kaplan, S Pawloski, PA Raebel, MA Scott, PE Smith, DH Toh, S Li, DK AF Avalos, Lyndsay A. Chen, Hong Yang, Chunmei Andrade, Susan E. Cooper, William O. Cheetham, Craig T. Davis, Robert L. Dublin, Sascha Hammad, Tarek A. Kaplan, Sigal Pawloski, Pamala A. Raebel, Marsha A. Scott, Pamela E. Smith, David H. Toh, Sengwee Li, De-Kun TI The Prevalence and Trends of Antiviral Medication Use During Pregnancy in the US: A Population-Based Study of 664,297 Deliveries in 2001-2007 SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE Antiviral medication; Exposure during pregnancy; Prevalence ID HEPATITIS-B-VIRUS; ACYCLOVIR EXPOSURE; BIRTH-DEFECTS; INFECTION; RISK; DATE AB To evaluate the prevalence, trends, timing and duration of exposure to antiviral medications during pregnancy within a US cohort of pregnant women and to evaluate the proportion of deliveries with a viral infection diagnosis among women given antiviral medication during pregnancy. Live-born deliveries between 2001 and 2007, to women aged 15-45 years, were included from the Medication Exposure in Pregnancy Risk Evaluation Program, a collaborative research program between the U.S. Food and Drug Administration and eleven health plans. They were evaluated for prevalence, timing, duration, and temporal trends of exposure to antiviral medications during pregnancy. We also calculated the proportion of deliveries with a viral infection diagnosis among those exposed to antiviral medications. Among 664,297 live births, the overall prevalence of antiviral exposure during pregnancy was 4 % (n = 25,155). Between 2001 and 2007, antiviral medication exposure during pregnancy doubled from 2.5 to 5 %. The most commonly used antiviral medication was acyclovir, with 3 % of the deliveries being exposed and most of the exposure occurring after the 1st trimester. Most deliveries exposed to antiviral medications were exposed for less than 30 days (2 % of all live births). Forty percent of the women delivering an infant exposed to antiviral medications had a herpes diagnosis. Our findings highlight the increased prevalence of women delivering an infant exposed to antiviral medications over time. These findings support the need for large, well-designed studies to assess the safety and effectiveness of these medications during pregnancy. C1 [Avalos, Lyndsay A.; Chen, Hong; Yang, Chunmei; Li, De-Kun] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. [Andrade, Susan E.] Meyers Primary Care Inst, Worcester, MA USA. [Andrade, Susan E.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Cooper, William O.] Vanderbilt Univ, Sch Med, Dept Pediat & Prevent Med, Nashville, TN 37212 USA. [Cheetham, Craig T.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA. [Davis, Robert L.] Kaiser Permanente Georgia, Ctr Hlth Res, Atlanta, GA USA. [Dublin, Sascha] Grp Hlth Res Inst, Seattle, WA USA. [Hammad, Tarek A.; Kaplan, Sigal; Scott, Pamela E.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Pawloski, Pamala A.] HealthPartners Res Fdn, Minneapolis, MN USA. [Raebel, Marsha A.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Smith, David H.] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR USA. [Toh, Sengwee] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Toh, Sengwee] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Li, De-Kun] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA. RP Avalos, LA (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM Lyndsay.A.Avalos@kp.org RI Toh, Sengwee/D-7567-2017 OI Toh, Sengwee/0000-0002-5160-0810 FU NCATS NIH HHS [UL1 TR001082]; NIA NIH HHS [K23 AG028954, K23AG028954]; NICHD NIH HHS [K12 HD052163, K12HD052163] NR 21 TC 2 Z9 2 U1 0 U2 7 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 EI 1573-6628 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD JAN PY 2014 VL 18 IS 1 BP 64 EP 72 DI 10.1007/s10995-013-1234-9 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 283MG UT WOS:000329249600009 PM 23420306 ER PT J AU Fang, Y Karim, KS Badano, A AF Fang, Yuan Karim, Karim S. Badano, Aldo TI Effect of burst and recombination models for Monte Carlo transport of interacting carriers in a-Se x-ray detectors on Swank noise SO MEDICAL PHYSICS LA English DT Article DE Swank noise; semiconductor detector; Monte Carlo; amorphous Selenium ID AMORPHOUS SELENIUM; PHOTOGENERATION; IONS AB Purpose: The authors describe the modification to a previously developed Monte Carlo model of semiconductor direct x-ray detector required for studying the effect of burst and recombination algorithms on detector performance. This work provides insight into the effect of different charge generation models for a-Se detectors on Swank noise and recombination fraction. Methods: The proposed burst and recombination models are implemented in the Monte Carlo simulation package, ARTEMIS, developed by Fang et al. ["Spatiotemporal Monte Carlo transport methods in x-ray semiconductor detectors: Application to pulse-height spectroscopy in a-Se," Med. Phys. 39(1), 308-319 (2012)]. The burst model generates a cloud of electron-hole pairs based on electron velocity, energy deposition, and material parameters distributed within a spherical uniform volume (SUV) or on a spherical surface area (SSA). A simple first-hit (FH) and a more detailed but computationally expensive nearest-neighbor (NN) recombination algorithms are also described and compared. Results: Simulated recombination fractions for a single electron-hole pair show good agreement with Onsager model for a wide range of electric field, thermalization distance, and temperature. The recombination fraction and Swank noise exhibit a dependence on the burst model for generation of many electron-hole pairs from a single x ray. The Swank noise decreased for the SSA compared to the SUV model at 4 V/mu m, while the recombination fraction decreased for SSA compared to the SUV model at 30 V/mu m. The NN and FH recombination results were comparable. Conclusions: Results obtained with the ARTEMIS Monte Carlo transport model incorporating drift and diffusion are validated with the Onsager model for a single electron-hole pair as a function of electric field, thermalization distance, and temperature. For x-ray interactions, the authors demonstrate that the choice of burst model can affect the simulation results for the generation of many electron-hole pairs. The SSA model is more sensitive to the effect of electric field compared to the SUV model and that the NN and FH recombination algorithms did not significantly affect simulation results. (C) 2014 American Association of Physicists in Medicine. C1 [Fang, Yuan; Badano, Aldo] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Fang, Yuan; Karim, Karim S.] Univ Waterloo, Dept Elect & Comp Engn, Waterloo, ON N2L 3G1, Canada. RP Fang, Y (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yuan.fang@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 FU Natural Sciences and Engineering Research Council of Canada (NSERC); Research Participation Program at the Center for Device and Radiological Health FX The author (Y.F.) would like to acknowledge funding by an appointment to the Research Participation Program at the Center for Device and Radiological Health administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the (U.S.) Department of Energy (DOE) and U.S. Food and Drug Administration. This work was also financially supported in part by the Natural Sciences and Engineering Research Council of Canada (NSERC). The mention of commercial products herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services. This is a contribution of the U.S. Food and Drug Administration and is not subject to copyright. NR 22 TC 0 Z9 0 U1 0 U2 3 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 J9 MED PHYS JI Med. Phys. PD JAN PY 2014 VL 41 IS 1 AR 011904 DI 10.1118/1.4842435 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 282OT UT WOS:000329182200025 PM 24387512 ER PT J AU Du, DY Wagoner, A Barone, SB Zinderman, CE Kelman, JA MaCurdy, TE Forshee, RA Worrall, CM Izurieta, HS AF Du, Dongyi (Tony) Wagoner, Austin Barone, Samuel B. Zinderman, Craig E. Kelman, Jeffrey A. MaCurdy, Thomas E. Forshee, Richard A. Worrall, Chris M. Izurieta, Hector S. TI Incidence of Endophthalmitis after Corneal Transplant or Cataract Surgery in a Medicare Population SO OPHTHALMOLOGY LA English DT Article ID ONSET POSTOPERATIVE ENDOPHTHALMITIS; VISUAL-ACUITY OUTCOMES; PENETRATING KERATOPLASTY; FUNGAL ENDOPHTHALMITIS; NATIONAL OUTCOMES; RETINAL-DETACHMENT; EXTRACTION; KERATITIS; BACTERIAL AB Objective: To estimate the incidence of infectious endophthalmitis after corneal transplant or cataract surgery, to evaluate the trend of endophthalmitis during the study period, and to assess demographic risk factors for endophthalmitis after surgeries. Design: A retrospective population-based cohort study. Participants and Controls: Study cohorts were derived from the Medicare claims databases, 2006 to 2011. Patients were continuously enrolled in Medicare Part A, Part B, and Part D. Patients undergoing corneal transplant or cataract surgery were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure codes. Methods: Endophthalmitis was defined in 3 different ways: (1) using ICD-9-CM codes (sensitive definition), (2) combining ICD-9-CM codes with Current Procedural Terminology, Fourth Edition (CPT-4) codes (specific definition), or (3) combining ICD-9-CM codes with antifungal prescriptions for endophthalmitis caused by fungal infection. Demographic risk factors for endophthalmitis were examined using multivariate Cox models. Main Outcome Measures: Incidence rates of endophthalmitis were calculated and compared for each definition of endophthalmitis at 6-week and 6-month intervals after corneal transplant or cataract surgery. Results: The infectious endophthalmitis incidence rates ranged from 0.11% to 1.05% in the corneal transplant cohort, 0.06% to 0.20% in the cataract surgery cohort, and 0.16% to 0.68% in the concurrent surgery cohort, depending on the definition and time interval after surgery. Compared with the cataract surgery cohort, the corneal transplant cohort had a higher adjusted hazard ratio (HR) of endophthalmitis within the 6-week postoperative interval (HR, 2.744; 95% confidence interval [CI], 1.544-4.880 in the sensitive definition and HR, 2.792; 95% CI, 1.146-6.802 in the specific definition) and within the 6-month postoperative interval (HR, 4.607; 95% CI, 3.144-6.752 for the sensitive definition and HR, 4.385; 95% CI, 2.245-8.566 for the specific definition). Conclusions: It is possible to monitor the trend of infectious endophthalmitis after corneal transplant or cataract surgery through examining Medicare claims databases as long as a consistent definition of endophthalmitis is used. The annual incidence of endophthalmitis was stable over time during the study period for both corneal transplant and cataract surgery procedures; however, there was a wider year-to-year variation for the corneal transplant cohort. (C) 2014 by the American Academy of Ophthalmology. C1 [Du, Dongyi (Tony); Zinderman, Craig E.; Forshee, Richard A.; Izurieta, Hector S.] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Wagoner, Austin] Acumen LLC, Berkeley, CA USA. [Barone, Samuel B.] US FDA, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Kelman, Jeffrey A.; Worrall, Chris M.] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. [MaCurdy, Thomas E.] Stanford Univ, Dept Econ, Stanford, CA 94305 USA. RP Du, DY (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, WOC1 RM343N HFM 222,1401 Rockville Pike, Rockville, MD 20852 USA. EM dongyi.du@fda.hhs.gov NR 25 TC 16 Z9 16 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 2014 VL 121 IS 1 BP 290 EP 298 DI 10.1016/j.ophtha.2013.07.016 PG 9 WC Ophthalmology SC Ophthalmology GA 282KG UT WOS:000329169500047 PM 23993357 ER PT J AU McClure, DL Raebel, MA Yih, WK Shoaibi, A Mullersman, JE Anderson-Smits, C Glanz, JM AF McClure, David L. Raebel, Marsha A. Yih, W. Katherine Shoaibi, Azadeh Mullersman, Jerald E. Anderson-Smits, Colin Glanz, Jason M. TI Mini-Sentinel methods: framework for assessment of positive results from signal refinement SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Editorial Material ID VACCINE SAFETY; FOOD; SURVEILLANCE; DATALINK C1 [McClure, David L.] Marshfield Clin Res Fdn, Marshfield Epidemiol Res Ctr, Marshfield, WI 54449 USA. [Raebel, Marsha A.; Glanz, Jason M.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Raebel, Marsha A.] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Aurora, CO USA. [Yih, W. Katherine] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Yih, W. Katherine] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Shoaibi, Azadeh] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Mullersman, Jerald E.] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD USA. [Mullersman, Jerald E.] E Tennessee State Univ, Quillen Coll Med, Dept Pathol, Johnson City, TN 37614 USA. [Anderson-Smits, Colin] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Glanz, Jason M.] Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA. RP McClure, DL (reprint author), Marshfield Clin Res Fdn, Epidemiol Res Ctr ML2, 1000 North Oak Ave, Marshfield, WI 54449 USA. EM mcclure.david@marshfieldclinic.org FU PHS HHS [HHSF223200910006I] NR 24 TC 3 Z9 3 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 JAN PY 2014 VL 23 IS 1 BP 3 EP 8 DI 10.1002/pds.3547 PG 6 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 282ND UT WOS:000329177700002 PM 24395545 ER PT J AU Briesacher, BA Soumerai, SB Zhang, F Toh, S Andrade, SE Wagner, JL Shoaibi, A Gurwitz, JH AF Briesacher, Becky A. Soumerai, Stephen B. Zhang, Fang Toh, Sengwee Andrade, Susan E. Wagner, Joann L. Shoaibi, Azadeh Gurwitz, Jerry H. TI Critically reviewing impact of regulatory actions, not just FDA's Response SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Letter C1 [Briesacher, Becky A.; Andrade, Susan E.; Gurwitz, Jerry H.] Univ Massachusetts, Sch Med, Div Geriatr Med, Worcester, MA 01605 USA. [Briesacher, Becky A.; Andrade, Susan E.; Wagner, Joann L.; Gurwitz, Jerry H.] Meyers Primary Care Inst, Worcester, MA USA. [Briesacher, Becky A.; Andrade, Susan E.; Wagner, Joann L.; Gurwitz, Jerry H.] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Soumerai, Stephen B.; Zhang, Fang; Toh, Sengwee] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Soumerai, Stephen B.; Zhang, Fang; Toh, Sengwee] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Shoaibi, Azadeh] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Briesacher, BA (reprint author), Univ Massachusetts, Sch Med, Div Geriatr Med, Biotech 4,Suite 315,377 Plantat St, Worcester, MA 01605 USA. EM Becky.Briesacher@umassmed.edu RI Toh, Sengwee/D-7567-2017 OI Toh, Sengwee/0000-0002-5160-0810 FU PHS HHS [HHSF223200910006I] NR 1 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2014 VL 23 IS 1 BP 106 EP 106 DI 10.1002/pds.3519 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 282ND UT WOS:000329177700015 PM 24395548 ER PT J AU Iyasu, S Staffa, J Graham, D Shoaibi, A Levenson, M Chakravarty, A Hammad, TA AF Iyasu, Solomon Staffa, Judy Graham, Dave Shoaibi, Azadeh Levenson, Mark Chakravarty, Aloka Hammad, Tarek A. TI Drug risk assessment and data reuse SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Letter C1 [Iyasu, Solomon; Graham, Dave] US FDA, Off Pharmacovigilance & Epidemiol, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Staffa, Judy] US FDA, Div Epidemiol 2, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Shoaibi, Azadeh] US FDA, Off Med Policy, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Levenson, Mark; Chakravarty, Aloka] US FDA, Div Biometr 7, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Hammad, Tarek A.] Merck & Co Inc, Epidemiol, Merck Res Labs, Whitehouse Stn, NJ 08889 USA. RP Iyasu, S (reprint author), US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM Solomon.iyasu@fda.hhs.gov NR 2 TC 0 Z9 0 U1 0 U2 4 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 JAN PY 2014 VL 23 IS 1 BP 107 EP 108 DI 10.1002/pds.3518 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 282ND UT WOS:000329177700016 PM 24395549 ER PT J AU Chi, X Zhi, L Vostal, JG AF Chi, Xuan Zhi, Li Vostal, Jaroslav G. TI Human platelets pathogen reduced with riboflavin and ultraviolet light do not cause acute lung injury in a two-event SCID mouse model SO TRANSFUSION LA English DT Article ID APHERESIS PLATELETS; AMOTOSALEN HCL; A LIGHT; TRANSFUSION; MICE; INACTIVATION; MACROPHAGES; NEUTROPHILS; ACTIVATION; REDUCTION AB BackgroundPathogen reduction technologies (PRTs) can induce platelet (PLT) lesions that reduce PLT survival and recovery from circulation and may be associated with acute lung injury (ALI). Study Design and MethodsHuman PLTs (hPLTs) in plasma with or without single or multiple Mirasol PRT treatments were assessed in vitro by aggregation and percentage of P-selectin expression. In vivo studies included PLT recovery in SCID mice and assessment of ALI in a two-event mouse model in which the sensitizing event was lipopolysaccharide injection and the second event was infusion of Mirasol-treated hPLTs. ResultsA single-dose Mirasol treatment (5J/cm(2)) did not induce any change in aggregation in response to adenosine 5-diphosphate (ADP) while a five-times-repeat Mirasol treatment (5x) increased aggregation response to low concentration of ADP. Mirasol PLTs (1x-5x) had increased percentage of P-selectin-positive PLTs after treatment and decreased aggregation with TRAP as the agonist. In vivo recovery in SCID mice was reduced extensively with Mirasol treatments (1x and 5x). In the two-event model of ALI, only the 5x Mirasol PLTs accumulated in the lung and this was not accompanied by changes in lung histology or increases in MIP-2 levels in bronchoalveolar lavage fluid. ConclusionsMirasol PRT treatment induced PLT activation and reduced in vivo recovery in a SCID mouse model of transfusion. In our two-event mouse model of ALI, the 5x Mirasol hPLTs accumulated in the lung, but did not cause signs of ALI. The 1x Mirasol treatment did not lead to PLT lung accumulation or ALI in this model. C1 [Chi, Xuan; Zhi, Li; Vostal, Jaroslav G.] US FDA, Lab Cellular Hematol, Div Hematol, OBRR,Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Vostal, JG (reprint author), US FDA, Lab Cellular Hematol, Div Hematol, OBRR,Ctr Biol Evaluat & Res, Bldg 29,Room 321,HFM 335,8800 Rockville Pike, Bethesda, MD 20892 USA. EM jaroslav.vostal@fda.hhs.gov NR 28 TC 4 Z9 4 U1 0 U2 0 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 2014 VL 54 IS 1 BP 74 EP 85 DI 10.1111/trf.12242 PG 12 WC Hematology SC Hematology GA 285TU UT WOS:000329418700014 PM 23656563 ER PT J AU Volpe, DA Hamed, SS Zhang, LK AF Volpe, Donna A. Hamed, Salaheldin S. Zhang, Lei K. TI Use of Different Parameters and Equations for Calculation of IC50 Values in Efflux Assays: Potential Sources of Variability in IC50 Determination SO AAPS JOURNAL LA English DT Article DE Caco-2; drug interaction; IC50; inhibition; P-glycoprotein ID P-GLYCOPROTEIN INHIBITION; DRUG-DRUG INTERACTIONS; IN-VIVO PREDICTION; CACO-2 CELLS; GP INHIBITION; DIGOXIN-INTERACTIONS; PDE5 INHIBITORS; MDCK CELLS; VITRO; TRANSPORT AB Drug interactions due to efflux transporters may result in one drug increasing or decreasing the systemic exposure of a second drug. The potential for in vivo drug interactions is estimated through in vitro cell assays. Variability in in vitro parameter determination (e. g., IC50 values) among laboratories may lead to different conclusions in in vivo interaction predictions. The objective of this study was to investigate variability in in vitro inhibition potency determination that may be due to calculation methods. In a Caco-2 cell assay, the absorptive and secretive permeability of digoxin was measured in the presence of spironolactone, itraconazole and vardenafil. From the permeability data, the efflux ratio and net secretory flux where calculated for each inhibitor. IC50 values were then calculated using a variety of equations and software programs. All three drugs decreased the secretory transport of digoxin in a concentration-dependent manner while increasing digoxin's absorption to a lesser extent. The resulting IC50 values varied according to the parameter evaluated, whether percent inhibition or percent control was applied, and the computational IC50 equation. This study has shown that multiple methods used to quantitate the inhibition of drug efflux in a cell assay can result in different IC50 values. The variability in the results in this study points to a need to standardize any transporter assay and calculation methods within a laboratory and to validate the assay with a set of known inhibitors and non-inhibitors against a clinically relevant substrate. C1 [Volpe, Donna A.; Hamed, Salaheldin S.; Zhang, Lei K.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Volpe, DA (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM donna.volpe@fda.hhs.gov NR 57 TC 6 Z9 6 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD JAN PY 2014 VL 16 IS 1 BP 172 EP 180 DI 10.1208/s12248-013-9554-7 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 282IX UT WOS:000329165600019 PM 24338112 ER PT J AU Petrick, N Kim, HJG Clunie, D Borradaile, K Ford, R Zeng, RP Gavrielides, MA McNitt-Gray, MF Lu, ZQJ Fenimore, C Zhao, BS Buckler, AJ AF Petrick, Nicholas Kim, Hyun J. Grace Clunie, David Borradaile, Kristin Ford, Robert Zeng, Rongping Gavrielides, Marios A. McNitt-Gray, Michael F. Lu, Z. Q. John Fenimore, Charles Zhao, Binsheng Buckler, Andrew J. TI Comparison of 1D, 2D, and 3D Nodule Sizing Methods by Radiologists for Spherical and Complex Nodules on Thoracic CT Phantom Images SO ACADEMIC RADIOLOGY LA English DT Article DE Computer tomography; lung nodules; phantom study; volumetric tumor measurement ID LUNG-CANCER; PULMONARY NODULES; COMPUTED-TOMOGRAPHY; TREATMENT RESPONSE; TUMOR RESPONSE; 7TH EDITION; VOLUME; SEGMENTATION; BIOMARKER; SCANS AB Rationale and Objectives: To estimate and statistically compare the bias and variance of radiologists measuring the size of spherical and complex synthetic nodules. Materials and Methods: This study did not require the institutional review board approval. Six radiologists estimated the size of 10 synthetic nodules embedded within an anthropomorphic thorax phantom from computed tomography scans at 0.8- and 5-mm slice thicknesses. The readers measured the nodule size using unidimensional (1D) longest in-slice dimension, bidimensional (2D) area from longest in-slice and longest perpendicular dimension, and three-dimensional pp) semiautomated volume. lntercomparisons of bias (difference between average and true size) and variance among methods were performed after converting the 2D and 3D estimates to a compatible 1D scale. Results: The relative biases of radiologists with the 3D tool were -1.8%, -0.4%, -0.7%, -0.4%, and -1.6% for 10-mm spherical, 20-mm spherical, 20-mm elliptical, 10-mm lobulated, and 10-mm spiculated nodules compared to 1.4%, -0.1%, -26.5%, -7.8%, and -39.8% for 1D. The three-dimensional measurements were significantly less biased than 1D for elliptical, lobulated, and spiculated nodules. The relative standard deviations for 3D were 7.5%, 3.9%, 3.6%, 9.7%, and 8.3% compared to 5.7%, 2.6%, 20.3%, 5.3%, and 16.4% for 1D. Unidimensional sizing was significantly less variable than 3D for the lobulated nodule and significantly more variable for the ellipsoid and spiculated nodules. Three-dimensional bias and variability were smaller for thin 0.8-mm slice data compared to thick 5.0-mm data. Conclusions: The study shows that radiologist-controlled 3D volumetric lesion sizing can not only achieve smaller bias but also achieve similar or smaller variability compared to 1D sizing, especially for complex lesion shapes. C1 [Petrick, Nicholas; Zeng, Rongping; Gavrielides, Marios A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Kim, Hyun J. Grace; McNitt-Gray, Michael F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA 90095 USA. [Kim, Hyun J. Grace] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA USA. [Clunie, David; Borradaile, Kristin] CoreLab Partners Inc, Princeton, NJ USA. [Ford, Robert] Clin Trials Imaging Consulting LLC, Belle Mead, NJ USA. [Lu, Z. Q. John; Fenimore, Charles] NIST, Gaithersburg, MD 20899 USA. [Zhao, Binsheng] Columbia Univ, Med Ctr, Dept Radiol, New York, NY USA. [Buckler, Andrew J.] Elucid Bioimaging Inc, Wenham, MA USA. RP Petrick, N (reprint author), US FDA, Ctr Devices & Radiol Hlth, WO62-4118,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM nicholas.petrick@fda.hhs.gov RI Clunie, David/Q-2777-2015; OI Clunie, David/0000-0002-2406-1145; Buckler, Andrew/0000-0002-0786-4835; McNItt-Gray, Michael/0000-0003-3004-4613 FU U.S. Food and Drug Administration (FDA); National Institute of Biomedical Imaging and Bioengineering; National Cancer Institute through IAG [224-07-6030]; Center for Interventional Oncology at the National Institutes of Health (NIH); NIH; FDA FX The phantom data collection was funded though a Critical Path grant from the U.S. Food and Drug Administration (FDA). The intramural research program of the National Institute of Biomedical Imaging and Bioengineering, the National Cancer Institute through IAG no. 224-07-6030, the Center for Interventional Oncology at the National Institutes of Health (NIH) and an Interagency Agreement between the NIH and the FDA also provided partial support for this project. NR 26 TC 17 Z9 17 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD JAN PY 2014 VL 21 IS 1 BP 30 EP 40 DI 10.1016/j.acra.2013.09.020 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 280HI UT WOS:000329018900005 PM 24331262 ER PT J AU Xiong, HS Yu, LX Qu, HB AF Xiong, Haoshu Yu, Lawrence X. Qu, Haibin TI A weighting approach for chromatographic fingerprinting to ensure the quality consistency of botanical drug products SO ANALYTICAL METHODS LA English DT Article ID DANSHEN INJECTION; HERBAL MEDICINES; SIMILARITY AB The batch-to-batch quality consistency needs to be controlled to ensure the efficacy and safety of botanical drug products. Chromatographic fingerprinting is a powerful tool for characterizing complex chemical systems such as botanical drugs. This paper presented the combined use of a proposed weighting algorithm and multivariate statistical analysis on fingerprint data to achieve quality consistency evaluation of botanical drug products. A set of fingerprint data following multivariate normal distribution was simulated based on the real fingerprint data of a botanical drug product, Danshen injection. The weight of each peak was set based on its batch-to-batch peak variation. A principal component analysis (PCA) model was established, and the Hotelling T-2 and DModX statistics were applied to evaluate quality consistency. The effect of weighting on the monitoring capability of the two statistics was evaluated through monitoring simulated peak area variations. The results showed that both the two statistics were more sensitive to the characteristic peaks with smaller batch-to-batch peak variations. Hence the peaks with larger variability will be permitted to have a wider tolerance range of variation, while a more narrow range of variation was seen for the peaks with smaller variability among batches. Peak weighting combined with multivariate statistical analysis has overcome some drawbacks of the fingerprint similarity analysis method, and is worthy of application and recommendation for the quality consistency evaluation of botanical drug products. C1 [Xiong, Haoshu; Qu, Haibin] Zhejiang Univ, Coll Pharmaceut Sci, Pharmaceut Informat Inst, Hangzhou 310058, Zhejiang, Peoples R China. [Yu, Lawrence X.] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Qu, HB (reprint author), Zhejiang Univ, Coll Pharmaceut Sci, Pharmaceut Informat Inst, Hangzhou 310058, Zhejiang, Peoples R China. EM quhb@zju.edu.cn FU China International Science and Technology Cooperation Project [2010DFB33630] FX This work was financially supported by the China International Science and Technology Cooperation Project (no. 2010DFB33630). NR 24 TC 0 Z9 0 U1 4 U2 13 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 2014 VL 6 IS 2 BP 476 EP 481 DI 10.1039/c3ay41728j PG 6 WC Chemistry, Analytical; Food Science & Technology; Spectroscopy SC Chemistry; Food Science & Technology; Spectroscopy GA 281AP UT WOS:000329072200021 ER PT J AU Corton, JC Cunningham, ML Hummer, BT Lau, C Meek, B Peters, JM Popp, JA Rhomberg, L Seed, J Klaunig, JE AF Corton, J. Christopher Cunningham, Michael L. Hummer, B. Timothy Lau, Christopher Meek, Bette Peters, Jeffrey M. Popp, James A. Rhomberg, Lorenz Seed, Jennifer Klaunig, James E. TI Mode of action framework analysis for receptor-mediated toxicity: The peroxisome proliferator-activated receptor alpha (PPAR alpha) as a case study SO CRITICAL REVIEWS IN TOXICOLOGY LA English DT Review DE Di(2-ethylhexyl) phthalate (DEHP); human relevancy framework; key events; liver cancer; mode of action; NF-kB; oxidative stress; peroxisome proliferator-activated receptor alpha (PPAR alpha) ID NF-KAPPA-B; ACYL-COA OXIDASE; TUMOR-NECROSIS-FACTOR; JUNCTIONAL INTERCELLULAR COMMUNICATION; CONSTITUTIVE ANDROSTANE RECEPTOR; <4-CHLORO-6-(2,3-XYLIDINO)-2-PYRIMIDINYLTHIO>ACETIC ACID WY-14,643; CIPROFIBRATE-INDUCED HEPATOCARCINOGENESIS; CORONARY-HEART-DISEASE; RETINOID-X-RECEPTOR; TRANSFERASE TRANSPEPTIDASE ACTIVITY AB Several therapeutic agents and industrial chemicals induce liver tumors in rodents through the activation of the peroxisome proliferator-activated receptor alpha (PPAR alpha). The cellular and molecular events by which PPAR alpha activators induce rodent hepatocarcinogenesis has been extensively studied and elucidated. This review summarizes the weight of evidence relevant to the hypothesized mode of action (MOA) for PPAR alpha activator-induced rodent hepatocarcinogenesis and identifies gaps in our knowledge of this MOA. Chemical-specific and mechanistic data support concordance of temporal and dose-response relationships for the key events associated with many PPAR alpha activators including a phthalate ester plasticizer di(2-ethylhexyl) phthalate (DEHP) and the drug gemfibrozil. While biologically plausible in humans, the hypothesized key events in the rodent MOA, for PPAR alpha activators, are unlikely to induce liver tumors in humans because of toxicodynamic and biological differences in responses. This conclusion is based on minimal or no effects observed on growth pathways, hepatocellular proliferation and liver tumors in humans and/or species (including hamsters, guinea pigs and cynomolgous monkeys) that are more appropriate human surrogates than mice and rats at overlapping dose levels. Overall, the panel concluded that significant quantitative differences in PPAR alpha activator-induced effects related to liver cancer formation exist between rodents and humans. On the basis of these quantitative differences, most of the workgroup felt that the rodent MOA is "not relevant to humans'' with the remaining members concluding that the MOA is "unlikely to be relevant to humans''. The two groups differed in their level of confidence based on perceived limitations of the quantitative and mechanistic knowledge of the species differences, which for some panel members strongly supports but cannot preclude the absence of effects under unlikely exposure scenarios. C1 [Corton, J. Christopher; Lau, Christopher; Seed, Jennifer] US EPA, Res Triangle Pk, NC 27711 USA. [Cunningham, Michael L.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Hummer, B. Timothy] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Meek, Bette] Univ Ottawa, McLaughlin Ctr Populat Hlth Risk Assessment, Ottawa, ON, Canada. [Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. [Popp, James A.] Stratoxon LLC, Lancaster, PA USA. [Rhomberg, Lorenz] Gradient Corp, Cambridge, MA 02138 USA. [Klaunig, James E.] Indiana Univ, Dept Environm Hlth, Indianapolis, IN 46204 USA. RP Corton, JC (reprint author), US EPA, Natl Hlth & Environm Effects Res Lab, 109 TW Alexander Dr,MD B105-03, Res Triangle Pk, NC 27711 USA. EM corton.chris@epa.gov; jklauni@indiana.edu FU Alliance for Risk Assessment (ARA); American Chemistry Council (ACC) Center for Advancing Risk Assessment; CropLife America; CXR Biosciences; Dow Chemical Company; DuPont; Hamner Institute for Health; Indiana University Department of Environmental Health; Society for Risk Analysis (SRA); Society of Toxicology (SOT); 3M Company; Toxicology Excellence for Risk Assessment (TERA); U.S. EPA National Health and Environmental Effects Research Laboratory (NHEERL); U.S. EPA Office of Chemical Safety and Pollution Prevention (OCSPP); U.S. EPA Office of Water (OW); TERA FX The employment affiliations of the authors are shown on the cover page. However, this manuscript, including all analyses, interpretations and opinions expressed are exclusively the work product of the authors and are not necessarily those of their employers or respective institutions. Funding and/or in-kind support for the workshop and this manuscript (but not to the coauthors) were provided by the Alliance for Risk Assessment (ARA), American Chemistry Council (ACC) Center for Advancing Risk Assessment, CropLife America, CXR Biosciences, The Dow Chemical Company, DuPont, The Hamner Institute for Health, Indiana University Department of Environmental Health, Society for Risk Analysis (SRA), Society of Toxicology (SOT), 3M Company, Toxicology Excellence for Risk Assessment (TERA), U.S. EPA National Health and Environmental Effects Research Laboratory (NHEERL), U.S. EPA Office of Chemical Safety and Pollution Prevention (OCSPP) and U.S. EPA Office of Water (OW). The National Institute of Environmental Health Sciences (NIEHS) provided the workshop venue. Several of the manuscript authors are employed by the institutions that provided funding for the workshop. Some of the authors of this manuscript have consulted for government and industry on receptor-specific related projects, have been or are funded through grants and by organizations mentioned earlier and/or have served as reviewers or on committees for related topics. Toxicology Excellence for Risk Assessment (TERA) was provided funding to organize and run the workshop. Some case study panel members were offered funding for travel and lodging associated with the workshop; some of the members accepted this funding. Funding was also utilized by TERA to coordinate and draft workshop manuscripts. Additional funding was supplied by The Dow Chemical Company, 3M Company and DuPont to finalize and submit the manuscripts. There was no input or review of the manuscripts by these sponsors. This manuscript was reviewed by the National Health and Environmental Effects Research Laboratory, U. S. Environmental Protection Agency and the NIEHS prior to submission, as a matter of protocol; however, none of those internal reviews altered the scientific conclusions NR 381 TC 34 Z9 34 U1 3 U2 38 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1040-8444 EI 1547-6898 J9 CRIT REV TOXICOL JI Crit. Rev. Toxicol. PD JAN PY 2014 VL 44 IS 1 BP 1 EP 49 DI 10.3109/10408444.2013.835784 PG 49 WC Toxicology SC Toxicology GA 281XG UT WOS:000329133700001 PM 24180432 ER PT J AU Mahmood, I AF Mahmood, I. TI Designing first-in-human dose of coagulation factors: application of pharmacokinetic allometric scaling SO HAEMOPHILIA LA English DT Article DE clearance; coagulation factors; first-in-human dose; interspecies scaling; pharmacokinetics; rule of exponent ID FC FUSION PROTEIN; HEMOPHILIA-B PATIENTS; RECOMBINANT FACTOR-IX; ACTIVATED FACTOR-VII; PROLONGED HALF-LIFE; RIX-FP; HUMANS; SAFETY; CLEARANCE; TRIAL AB The objectives of this study were to (i) evaluate the predictive performance of pharmacokinetic interspecies scaling of coagulation factors to predict clearance (CL) and (ii) project first-in-human dose based on the predicted human CL. Human CL of nine coagulation factors was predicted using two or three animal species using two methods: (i) CL vs. body weight (simple allometry) and where applicable (ii) the product of CL and brain weight vs. body weight. Based on the predicted human CL, four methods were used to project the first-in-human dose. The predicted pharmacokinetic parameters and the estimated first-in-human dose of coagulation factors were compared with the observed human values obtained from clinical trials. The results of the study indicated that the CL of coagulation factors can be predicted with reasonable accuracy in humans and a good estimate of first-in-human dose can be obtained from the predicted human CL. The suggested methods in this study are not only time and cost-effective but also provide rational alternatives to the somewhat arbitrary dose selection process for coagulation factors often used. C1 [Mahmood, I.] US FDA, Off Blood Review & Res OBRR, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Mahmood, I (reprint author), US FDA, Off Blood Review & Res OBRR, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM iftekhar.mahmood@fda.hhs.gov NR 30 TC 1 Z9 1 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-8216 EI 1365-2516 J9 HAEMOPHILIA JI Haemophilia PD JAN PY 2014 VL 20 IS 1 BP 32 EP 38 DI 10.1111/hae.12231 PG 7 WC Hematology SC Hematology GA 276FG UT WOS:000328733300009 PM 23855969 ER PT J AU Ponce, RA Gelzleichter, T Haggerty, HG Heidel, S Holdren, MS Lebrec, H Mellon, RD Pallardy, M AF Ponce, Rafael A. Gelzleichter, Thomas Haggerty, Helen G. Heidel, Shawn Holdren, Matthew S. Lebrec, Herve Mellon, R. Daniel Pallardy, Marc TI Immunomodulation and lymphoma in humans SO JOURNAL OF IMMUNOTOXICOLOGY LA English DT Review DE Human; immune modulation; lymphoma ID EPSTEIN-BARR-VIRUS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; HUMAN-IMMUNODEFICIENCY-VIRUS; CLASS-SWITCH RECOMBINATION; NON-HODGKINS-LYMPHOMA; NECROSIS FACTOR THERAPY; CENTER B-CELLS; COMMON VARIABLE IMMUNODEFICIENCY; CANCER-RELATED INFLAMMATION; GERMINAL CENTER REACTION AB Observational and clinical studies have associated increased cancer risks with primary or acquired immunodeficiencies, autoimmunity, and use of immunotherapies to treat chronic inflammation (e.g. autoimmunity) or support organ engraftment. Understanding of the relationship between immune status and cancer risk is generally grounded in two juxtaposing paradigms: that the immune system protects the host via surveillance of tumors and oncogenic viruses (e.g. immunosurveillance model) and that chronic inflammation can augment tumor growth and metastasis (inflammation model). Whereas these models support a role of immune status in many cancers, they are insufficient to explain the disproportionate increase in B-cell lymphoma risk observed across patient populations with either chronic immunosuppression or inflammation. Evaluation for the presence of Epstein-Barr virus (EBV) in lymphomas obtained from various populations demonstrates a variable role for the virus in lymphomagenesis across patient populations. An evaluation of the DNA alterations found in lymphomas and an understanding of B-cell ontogeny help to provide insight into the unique susceptibility of lymphocytes, primarily B-cells, to oncogenic transformation. EBV-independent B-cell oncogenic transformation is driven by chronic antigenic stimulation due to either inflammation (as seen in patients with autoimmune disease or a tissue allograft) or to unresolved infection (as seen in immunosuppressed patients), and the transformation arises as a result of DNA damage from genomic recombination and mutation during class switching and somatic hypermutation. This model explains the increased background rate of lymphoma in some patients with autoimmunity, and highlights the challenge of resolving the confounding that occurs between disease severity and use of targeted immunotherapies to treat chronic inflammation. The ability to distinguish between disease-and treatment-related risk of lymphoma and an appreciation of the etiology of B-cell transformation is central to an improved risk assessment by scientists, clinicians and regulators, including the approval, labeling, and chronic use of immunotherapies. C1 [Ponce, Rafael A.; Lebrec, Herve] Amgen Inc, Seattle, WA 98119 USA. [Gelzleichter, Thomas] Genentech Inc, Brisbane, CA USA. [Haggerty, Helen G.] Bristol Myers Squibb Co, New Brunswick, NJ USA. [Heidel, Shawn] Covance Labs Inc, Greenfield, IN USA. [Holdren, Matthew S.] Bristol Myers Squibb Co, Mt Vernon, IA USA. [Mellon, R. Daniel] US FDA, DAAAP, Off Drug Evaluat 2, Off New Drugs,Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Pallardy, Marc] Univ Paris, Fac Pharm, Paris, France. RP Ponce, RA (reprint author), Amgen Inc, 1201 Amgen Court West,AW1 J3120, Seattle, WA 98119 USA. EM rponce@amgen.com NR 141 TC 6 Z9 6 U1 0 U2 7 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1547-691X EI 1547-6901 J9 J IMMUNOTOXICOL JI J. Immunotoxicol. PD JAN-MAR PY 2014 VL 11 IS 1 BP 1 EP 12 DI 10.3109/1547691X.2013.798388 PG 12 WC Toxicology SC Toxicology GA 279FH UT WOS:000328945300001 PM 23746314 ER PT J AU Prater, SN Banugaria, SG Morgan, C Sung, CC Rosenberg, AS Kishnani, PS AF Prater, Sean N. Banugaria, Suhrad G. Morgan, Claire Sung, Crystal C. Rosenberg, Amy S. Kishnani, Priya S. TI Letter to the Editors: Concerning "CRIM-negative Pompe disease patients with satisfactory clinical outcomes on enzyme replacement therapy" by Al Khallaf et al SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Letter C1 [Prater, Sean N.; Banugaria, Suhrad G.; Kishnani, Priya S.] Duke Univ, Med Ctr, Dept Pediat, Div Med Genet, Durham, NC 27710 USA. [Morgan, Claire; Sung, Crystal C.] Genzyme Corp, Boston, MA USA. [Rosenberg, Amy S.] US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Kishnani, PS (reprint author), Duke Univ, Med Ctr, Dept Pediat, Div Med Genet, Durham, NC 27710 USA. EM kishn001@mc.duke.edu FU NINDS NIH HHS [U54 NS065768, U54NS065768] NR 7 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 EI 1573-2665 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD JAN PY 2014 VL 37 IS 1 BP 141 EP 143 DI 10.1007/s10545-013-9637-8 PG 3 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 281KN UT WOS:000329100200019 PM 23887636 ER PT J AU Grigorenko, E Fisher, C Patel, S Chancey, C Rios, M Nakhasi, HL Duncan, RC AF Grigorenko, Elena Fisher, Carolyn Patel, Sunali Chancey, Caren Rios, Maria Nakhasi, Hira L. Duncan, Robert C. TI Multiplex Screening for Blood-Borne Viral, Bacterial, and Protozoan Parasites using an Open Array Platform SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID WEST-NILE-VIRUS; REAL-TIME PCR; HEPATITIS-C-VIRUS; INTERNATIONAL STANDARD; WORKING REAGENTS; RNA; ASSAY; DNA; LEISHMANIA; HIV-1 AB The use of nucleic acid tests for detection of pathogens has improved the safety of blood products. However, ongoing pathogen emergence demonstrates a need for development of devices testing for multiple pathogens simultaneously. One approach combines two proven technologies: Taqman chemistry for target identification and quantification and the OpenArray nanofluidic real-time PCR platform for spatial multiplexing of assays. A panel of Taqman assays was developed to detect nine blood-borne pathogens (BBPs): four viral, two bacterial, and three protozoan parasites. The custom BBP OpenArray plate with 18 assays was tested for specificity and analytical sensitivity for nucleic acid from each purified pathogen and with pathogen-spiked human blood and plasma samples. For most targets, the Limits of detection (10 to 10,000 copies/mL) were comparable with existing real-time platforms. The testing of the BBP OpenArray with pathogen-spiked coded human plasma or blood samples and negative control specimens demonstrated no false-positive results among the samples tested and correctly identified pathogens with the lowest concentration detected ranging from 10 cells/mL (Trypanosoma cruzi) to 10,000 cells/mL (Escherichia coli). These results represent a proof of concept that indicated the BBP OpenArray platform in combination with Taqman chemistry may provide a multiplex real-time PCR pathogen detection method that pints the way for a next-generation platform for infectious disease testing in blood. C1 [Grigorenko, Elena; Patel, Sunali] Life Technol Corp, San Francisco, CA USA. [Fisher, Carolyn; Chancey, Caren; Rios, Maria; Nakhasi, Hira L.; Duncan, Robert C.] US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Bethesda, MD USA. RP Duncan, RC (reprint author), 1401 Rockville Pike,HFM310, Rockville, MD 20852 USA. EM robert.duncan@fda.hhs.gov RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 FU internal FDA grant under the Modernizing Science Program FX Supported in part by an internal FDA grant under the Modernizing Science Program. NR 34 TC 10 Z9 10 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD JAN PY 2014 VL 16 IS 1 BP 136 EP 144 DI 10.1016/j.jmoldx.2013.08.002 PG 9 WC Pathology SC Pathology GA 278YT UT WOS:000328926500015 PM 24184228 ER PT J AU Lucas, CL Kuehn, HS Zhao, F Niemel, JE Deenick, EK Palendira, U Avery, DT Moens, L Cannons, JL Lanai, MB Stoddard, J Ouyane, W Frucht, DM Rao, VK Atkinson, TP Agharahimi, A Hussey, AA Folioll, LR Olivier, KN Fleisher, TA Pittaluga, S Holland, SM Cohen, JI Oliveira, JB Tangye, SG Schwartzberg, PL Lenardol, MJ Uzel, G AF Lucas, Carrie L. Kuehn, Hye Sun Zhao, Fang Niemel, Julie E. Deenick, Elissa K. Palendira, Umaimainthan Avery, Danielle T. Moens, Leen Cannons, Jennifer L. Lanai, Matthew Bianca Stoddard, Jennifer Ouyane, Weiming Frucht, David M. Rao, V. Koneti Atkinson, T. Prescott Agharahimi, Anahita Hussey, Ashleigh A. Folioll, Les R. Olivier, Kenneth N. Fleisher, Thomas A. Pittaluga, Stefania Holland, Steven M. Cohen, Jeffrey I. Oliveira, Joao B. Tangye, Stuart G. Schwartzberg, Pamela L. Lenardol, Michael J. Uzel, Gulbu TI Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110 delta result in T cell senescence and human immunodeficiency SO NATURE IMMUNOLOGY LA English DT Article ID IMPAIRED B-CELL; PHOSPHOINOSITIDE 3-KINASE; P85-ALPHA SUBUNIT; CLASS IPI3K; P110 DELTA; MTOR; MEMORY; DIFFERENTIATION; KINASE; METABOLISM AB The p110 delta subunit of phosphatidylinositol-3-OH kinase (PI(3)K) is selectively expressed in leukocytes and is critical for lymphocyte biology. Here we report fourteen patients from seven families who were heterozygous for three different germline, gain-of-function mutations in PIK3CD (which encodes p110 delta). These patients presented with sinopulmonary infections, lymphadenopathy, nodular lymphoid hyperplasia and viremia due to cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV). Strikingly, they had a substantial deficiency in naive T cells but an over-representation of senescent effector T cells. In vitro, T cells from patients exhibited increased phosphorylation of the kinase Akt and hyperactivation of the metabolic checkpoint kinase mTOR, enhanced glucose uptake and terminal effector differentiation. Notably, treatment with rapamycin to inhibit mTOR activity in vivo partially restored the abundance of naive T cells, largely 'rescued' the in vitro T cell defects and improved the clinical course. C1 [Lucas, Carrie L.; Lanai, Matthew Bianca; Lenardol, Michael J.] NIAID, Immunol Lab, NIH, Mol Dev Immune Syst Sect, Bethesda, MD 20892 USA. [Kuehn, Hye Sun; Niemel, Julie E.; Stoddard, Jennifer; Fleisher, Thomas A.] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD USA. [Zhao, Fang; Cannons, Jennifer L.; Schwartzberg, Pamela L.] NHGRI, NIH, Genet Dis Res Branch, Cell Signaling Sect, Bethesda, MD 20892 USA. [Zhao, Fang] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Deenick, Elissa K.; Palendira, Umaimainthan; Avery, Danielle T.; Moens, Leen] Garvan Inst Med Res, Immunol & Immunodeficiency Grp, Program Immunol, Sydney, NSW, Australia. [Deenick, Elissa K.; Palendira, Umaimainthan] Univ New S Wales, Fac Med, St Vincents Clin Sch, Sydney, NSW, Australia. [Ouyane, Weiming; Frucht, David M.] United States Food & Drug Adm, Ctr Drug Evaluat & Res, Off Biotechnol Prod, Div Monoclonal Antibodies,Lab Cell Biol, Bethesda, MD USA. [Atkinson, T. Prescott] Univ Alabama Birmingham, Dept Pediat, Div Allergy & Immunol, Birmingham, AL USA. [Olivier, Kenneth N.; Holland, Steven M.] Frederick Natl Lab Clin Res, Sci Applicatidns Int Corp Frederick, Clin Monitoring Res Program, Clin Res Directorate,Lab Clin Infect Dis, Frederick, MD USA. [Agharahimi, Anahita] NIH, Ctr Clin, Bethesda, MD USA. [Folioll, Les R.] Natl Canc Inst, NIH, Pathol Lab, Bethesda, MD USA. [Pittaluga, Stefania] Natl Inst Allergy & Infect Dis, Natl Inst Hlth, Lab Infect Dis, Bethesda, MD USA. [Cohen, Jeffrey I.] Inst Med Integral Prof Fernando Figue, Recife Pernambuco, Brazil. RP Uzel, G (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM guzel@niaid.nih.gov RI Tangye, Stuart/H-4023-2014; OI Biancalana, Matthew/0000-0002-1078-1838; Oliveira, Joao/0000-0001-9388-8173; Ouyang, Wenjun/0000-0002-1811-5864; Niemela, Julie/0000-0003-4197-3792 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Clinical Center of the US National Institutes of Health; National Human Genome Research Institute of the US National Institutes of Health; Frederick National Laboratory for Cancer Research of the US National Institutes of Health [HHSN261200800001E]; National Health and Medical Research Council of Australia; Cancer Council NSW; Cancer Institute NSW; Research Foundation-Flanders, Belgium; National Institute of General Medical Sciences FX We thank the referring physicians, as well as the patients and families. Supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Clinical Center of the US National Institutes of Health (C.L.L., H.S.K., J.E.N., M.B., J.S., WO., V.K.R., A.A., A.A.H., K.N.O., T.A.F., S.P., S.M.H., J.I.C., M.J.L., G.U.), the National Human Genome Research Institute of the US National Institutes of Health (F.Z., J.L.C., P.L.S.), the Frederick National Laboratory for Cancer Research of the US National Institutes of Health (HHSN261200800001E), the National Health and Medical Research Council of Australia (E.K.D., UP., S.G.T.), Cancer Council NSW (S.G.T.), the Cancer Institute NSW (U.P.), the Research Foundation-Flanders, Belgium (L.M.) and the National Institute of General Medical Sciences (C.L.L. and R.Z.). The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. NR 48 TC 131 Z9 136 U1 2 U2 28 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2014 VL 15 IS 1 BP 88 EP 97 DI 10.1038/ni.2771 PG 10 WC Immunology SC Immunology GA 277DZ UT WOS:000328800500016 PM 24165795 ER PT J AU LaVange, LM AF LaVange, Lisa M. TI The Role of Statistics in Regulatory Decision Making SO THERAPEUTIC INNOVATION & REGULATORY SCIENCE LA English DT Article DE statistical reviews; regulatory guidance; data quality; sensitivity analysis; meta-analysis; missing data; adaptive design AB The number of statistical challenges facing regulators remains high, as does the importance of statistical thinking in the regulatory decision-making process. Statisticians in the Office of Biostatistics at the US Food and Drug Administration review hundreds of new drug and therapeutic biologic applications each year and advise sponsors on protocols numbering in the thousands. In addition to remaining up to date on the newest statistical methods, statisticians are often called upon for innovative approaches to difficult regulatory problems. This article presents the author's view of the important role that statisticians play in regulatory decision making, beginning with a broad overview of current office initiatives, including the development of guidance documents and a recent push for open and transparent collaboration with industry on methods development. Several recent examples are provided to illustrate the impact that statisticians can have on regulatory decisions through the use of strategic quantitative thinking. Also discussed are areas where it is believed that innovative statistical solutions or greater clarity on existing approaches is still needed. C1 US FDA, Off Biostat, OTS, CDER, Silver Spring, MD 20933 USA. RP LaVange, LM (reprint author), US FDA, Off Biostat, OTS, CDER, Bldg 21,Room 3554,10903 New Hampshire Ave, Silver Spring, MD 20933 USA. EM lisa.lavange@fda.hhs.gov FU US Food and Drug Administration (FDA) FX This study had no external funding source; it was funded entirely by the US Food and Drug Administration (FDA). The author is employed by the FDA. NR 36 TC 3 Z9 4 U1 2 U2 8 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 2014 VL 48 IS 1 BP 10 EP 19 DI 10.1177/2168479013514418 PG 10 WC Medical Informatics; Pharmacology & Pharmacy SC Medical Informatics; Pharmacology & Pharmacy GA 282II UT WOS:000329164100002 ER PT J AU Wang, SJ Hung, HMJ AF Wang, Sue-Jane Hung, H. M. James TI A Conditional Adaptive Weighted Test Method for Confirmatory Trials SO THERAPEUTIC INNOVATION & REGULATORY SCIENCE LA English DT Article DE adaptive statistical information design; consistency of treatment effects; down weighting at individual level; efficiency loss; firewalls for trial logistics ID SAMPLE-SIZE; CLINICAL-TRIALS AB The authors consider a statistically valid method that has little concern caused by down weighting in stage 2 or slight loss in efficiency and possibly improves power performance for a trial design that allows for adaptation of statistical information. In addition to the need for a priori sound data-based planning that accounts for limited uncertainty, the criteria for statistical information adaptation are scientifically sound and can foster transparent trial logistics that are necessary for such adaptation in confirmatory trials. A major rationale of the proposed conditional adaptive weighted test method is to increase the probability of success of an adequate and well-controlled confirmatory trial that may otherwise fall short of statistical significance despite initial rigorous planning for statistical information. C1 [Wang, Sue-Jane] US FDA, Off Biostat, OTS, CDER, Silver Spring, MD 20993 USA. [Hung, H. M. James] US FDA, Div Biometr 1, OB, OTS,CDER, Silver Spring, MD 20993 USA. RP Wang, SJ (reprint author), US FDA, Off Biostat, OTS, CDER, 10903 New Hampshire Ave,Bldg 21, Silver Spring, MD 20993 USA. EM suejane.wang@fda.hhs.gov FU RSR [06-14, 05-02, 05-12]; Center for Drug Evaluation and Research of the US Food and Drug Administration. FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The research work presented in this article was supported by the RSR funds # 06-14, # 05-02, and # 05-12, awarded by the Center for Drug Evaluation and Research of the US Food and Drug Administration. NR 9 TC 2 Z9 2 U1 0 U2 0 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 2014 VL 48 IS 1 BP 51 EP 55 DI 10.1177/2168479013513891 PG 5 WC Medical Informatics; Pharmacology & Pharmacy SC Medical Informatics; Pharmacology & Pharmacy GA 282II UT WOS:000329164100006 ER PT J AU Huang, L Guo, T Zalkikar, JN Tiwari, RC AF Huang, Lan Guo, Ted Zalkikar, Jyoti N. Tiwari, Ram C. TI A Review of Statistical Methods for Safety Surveillance SO THERAPEUTIC INNOVATION & REGULATORY SCIENCE LA English DT Article DE passive surveillance; disproportional signal; postmarket safety database; FDA Sentinel Initiative ID SIGNAL-DETECTION; RATIO TEST; REPORTING SYSTEM; DRUG; PHARMACOVIGILANCE; DATABASE; GENERATION; DISCOVERY; EVENTS; VAERS AB The data-mining statistical methods used for disproportionality analysis of drug-adverse event combinations from large drug safety databases such as the FDA's Adverse Event Reporting System (FAERS), consisting of spontaneous reports on adverse events for postmarket drugs, are called passive surveillance methods. However, the statistical signal detection methods for longitudinal data, as the data accrue in time, are called active surveillance methods. A review of the most commonly used passive surveillance statistical methods and the relationships among them is presented with unified notations. These methods are applied to the 2006-2012 FAERS data; the number of drug signals of disproportionate rates (SDRs) detected by each of these methods with the common SDRs from all of these methods, for the adverse event myocardial infarction, are given. Finally, there is a brief discussion on the recently developed active surveillance methods. C1 [Huang, Lan; Zalkikar, Jyoti N.] US FDA, Div Biostat 5, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Guo, Ted; Tiwari, Ram C.] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Huang, L (reprint author), US FDA, Div Biostat 5, Off Biostat, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,White Oak Bldg 21,Room 46, Silver Spring, MD 20993 USA. EM lan.huang@fda.hhs.gov NR 36 TC 4 Z9 4 U1 1 U2 7 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 2014 VL 48 IS 1 BP 98 EP 108 DI 10.1177/2168479013514236 PG 11 WC Medical Informatics; Pharmacology & Pharmacy SC Medical Informatics; Pharmacology & Pharmacy GA 282II UT WOS:000329164100012 ER PT J AU Wang, YMC Jawa, V Ma, M AF Wang, Yow-Ming C. Jawa, Vibha Ma, Mark TI Immunogenicity and PK/PD evaluation in biotherapeutic drug development: scientific considerations for bioanalytical methods and data analysis SO BIOANALYSIS LA English DT Review ID PHARMACOKINETIC ASSESSMENT; BIOTECHNOLOGY PRODUCTS; MONOCLONAL-ANTIBODIES; IN-VIVO; IMPACT; PHARMACODYNAMICS; IMMUNOASSAY; ASSAYS; OPTIMIZATION; DISPOSITION AB With the advent of novel technologies, considerable advances have been made in the evaluation of the relationship between PK and PD. Ligand-binding assays have been the primary assay format supporting PK and immunogenicity assessments. Critical and in-depth characterizations of the ligand-binding assay of interest can provide valuable understanding of the limitations, for interpreting PK/PD and immunogenicity results. This review illustrates key challenges with regard to understanding the relationship between anti-drug antibody and PK/PD, including confounding factors associated with the development and validation of ligand-binding assays, mechanisms by which anti-drug antibody impacts PK/PD, factors to consider during data analyses and interpretation, and a perspective on integrating immunogenicity data into the well-established quantitative modeling approach. Through recognizing these challenges, we propose some opportunities for improvements in the development and validation of fit-for-purpose bioanalytical methods. C1 [Wang, Yow-Ming C.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Jawa, Vibha] Amgen Inc, Dept Clin Immunol, Thousand Oaks, CA 91320 USA. [Ma, Mark] Amgen Inc, Dept Pharmacokinet & Drug Metab, Thousand Oaks, CA 91320 USA. RP Ma, M (reprint author), Amgen Inc, Dept Pharmacokinet & Drug Metab, 1 Amgen Ctr Dr, Thousand Oaks, CA 91320 USA. EM mark.ma@amgen.com NR 43 TC 7 Z9 7 U1 1 U2 9 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 EI 1757-6199 J9 BIOANALYSIS JI Bioanalysis PD JAN PY 2014 VL 6 IS 1 BP 79 EP 87 DI 10.4155/BIO.13.302 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 273ZG UT WOS:000328574200012 PM 24341496 ER PT J AU Mohan, KVK Rao, SS Gao, Y Atreya, CD AF Mohan, K. V. K. Rao, S. Sainath Gao, Y. Atreya, C. D. TI Enhanced antimicrobial activity of peptide-cocktails against common bacterial contaminants of ex vivo stored platelets SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Article DE Antimicrobial peptides; bactericidal; colony-forming units; pathogen reduction; platelet-derived peptides ID IN-VITRO ACTIVITIES; MICROBICIDAL PROTEINS; STAPHYLOCOCCUS-AUREUS; EXPERIMENTAL ENDOCARDITIS; INNATE IMMUNITY; ARGININE-RICH; SUSCEPTIBILITY; COMBINATION; MECHANISMS; RESISTANCE AB Bacterial contamination of blood components such as ex vivo-stored platelets is a major safety risk in transfusion medicine. We have recently shown that synthetic antimicrobial peptides named PD1-PD4 derived from the thrombin-induced human platelet-derived antimicrobial proteins, and repeats of Arg-Trp (RW1-RW5) demonstrate microbicidal activity against selected bacteria and viruses. In the present study, we selected PD3, PD4, RW2, RW3 and RW4 and evaluated each individual peptide and their various combinations to see whether the cocktail regimen enhances the antimicrobial activity above and over the individual peptides. Stored platelet or plasma samples spiked with known titres of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Bacillus cereus were treated with either individual peptides or with peptides in various combinations. Analyses revealed that individual peptides show moderate microbicidal activity (10- to 100-fold reduction) against the tested bacteria relative to their combined regimen. The peptide combinations (RW2+RW4, RW2+RW3+RW4 and PD4+RW3+RW4) on the other hand enhanced the microbicidal activity (c.10000-fold reduction) and revealed a minimal inhibitory concentration of 5M. Time-kill kinetics indicated that these three peptide combinations exhibited enhanced antimicrobial activity bringing about a 100-fold reduction of bacterial titres within 20min of incubation. The present study therefore demonstrates the synergistic effect of antimicrobial peptides when used in combinations and provides a proof-of-concept of its potential application as a molecular tool towards pathogen reduction and further extends the possibility of using peptide combinatorial therapeutics as broad-spectrum antibiotics or as alternatives to combat drug-resistant bacteria. C1 [Mohan, K. V. K.; Rao, S. Sainath; Atreya, C. D.] US FDA, Sect Cell Biol, Lab Cellular Hematol, Bethesda, MD 20014 USA. [Gao, Y.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Mohan, KVK (reprint author), Bldg 29A,Room 2C-15,NIH Campus,8800 Rockville Pik, Bethesda, MD 20892 USA. EM krishna.ketha@fda.hhs.gov FU Center for Biologics Evaluation and Research (CBER); US Department of Energy; US Food and Drug Administration FX SSR is a recipient of a postdoctoral fellowship at the Center for Biologics Evaluation and Research (CBER) administered by the Oak Ridge Institute for Science and Education through an intra-agency agreement between the US Department of Energy and the US Food and Drug Administration. Review of the manuscript by Drs Salim Haddad and Vladimir Lugovstev, of CBER, is highly appreciated. NR 30 TC 1 Z9 1 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1198-743X EI 1469-0691 J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD JAN PY 2014 VL 20 IS 1 BP O39 EP O46 DI 10.1111/1469-0691.12326 PG 8 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 273JK UT WOS:000328530900017 PM 23926880 ER PT J AU Manjanatha, MG Bishop, ME Pearce, MG Kulkarni, R Lyn-Cook, LE Ding, W AF Manjanatha, Mugimane G. Bishop, Michelle E. Pearce, Mason G. Kulkarni, Rohan Lyn-Cook, Lascelles E. Ding, Wei TI Genotoxicity of Doxorubicin in F344 Rats by Combining the Comet Assay, Flow-Cytometric Peripheral Blood Micronucleus Test, and Pathway-Focused Gene Expression Profiling SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE doxorubicin; comet assay; micronucleus assay; gene expression ID SPONTANEOUSLY HYPERTENSIVE-RATS; CONGESTIVE-HEART-FAILURE; CELL GEL-ELECTROPHORESIS; DNA-DAMAGE; IN-VITRO; INDUCED CARDIOTOXICITY; RENAL TOXICITY; ANTHRACYCLINE CARDIOTOXICITY; CHILDHOOD-CANCER; MULTIPLE ORGANS AB Doxorubicin (DOX) is an antineoplastic drug effective against many human malignancies. DOX's clinical efficacy is greatly limited because of severe cardiotoxicity. To evaluate if DOX is genotoxic in the heart, similar to 7-week-old, male F344 rats were administered intravenously 1, 2, and 3 mg/kg bw DOX at 0, 24, 48, and 69 hr and the Comet assays in heart, liver, kidney, and testis and micronucleus (MN) assay in the peripheral blood (PB) erythrocytes using flow cytometry were conducted. Rats were euthanized at 72 hr and PB was removed for the MN assay and single cells were isolated from multiple tissues for the Comet assays. None of the doses of DOX induced a significant DNA damage in any of the tissues examined by the alkaline Comet assay. Contrastingly, the glycosylase enzymes-modified Comet assay showed a significant dose dependent increase in the oxidative DNA damage in the cardiac tissue (P 0.05). In the liver, only the top dose induced significant increase in the oxidative DNA damage (P 0.05). The histopathology showed no severe cardiotoxicity but non-neoplastic lesions were present in both untreated and treated samples. A severe toxicity likely occurred in the bone marrow because no viable reticulocytes could be screened for the MN assay. Gene expression profiling of the heart tissues showed a significant alteration in the expression of 11 DNA damage and repair genes. These results suggest that DOX is genotoxic in the heart and the DNA damage may be induced primarily via the production of reactive oxygen species. Environ. Mol. Mutagen. 55:24-34, 2014. (c) 2013 Wiley Periodicals, Inc.(dagger 99.9%, Positive Predictive Value of 99.7%, and an overall score (average of sensitivity and Positive Predictive Value) of 99.8% when applied to the training set. The best overall performance on the test sets were: 88.9%, 76.3% and 84.4% for phases I, II and Ill, respectively. We developed a robust heart beat detector that fuses annotations from multiple individual detectors. The algorithm improves the training results compared to ECG detections alone, and performs well on the test sets. Data fusion approaches like this one can improve patient monitoring and reduce false alarms. C1 [Johannesen, Lars; Vicente, Jose; Scully, Christopher G.; Galeotti, Loriano; Strauss, David G.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Johannesen, Lars] Karolinska Inst, Dept Clin Physiol, S-10401 Stockholm, Sweden. [Johannesen, Lars] Karolinska Univ Hosp, Stockholm, Sweden. [Johannesen, Lars] Univ Zaragoza, IIS Aragon, BSICoS Grp, Aragon Inst Engn Res I3A, Zaragoza, Aragon, Spain. RP Johannesen, L (reprint author), Bldg 62,RM 1125C,10993 New Hampshire Ave, Silver Spring, MD 20910 USA. EM Lars.johannesen@fda.hhs.gov NR 8 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2325-887X BN 978-1-4799-4346-3 J9 COMPUT CARDIOL CONF PY 2014 VL 41 BP 277 EP 280 PG 4 WC Cardiac & Cardiovascular Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology SC Cardiovascular System & Cardiology; Computer Science; Mathematical & Computational Biology GA BE2TW UT WOS:000370068300071 ER PT S AU Scully, CG Kramer, GC Strauss, DG AF Scully, Christopher G. Kramer, George C. Strauss, David G. BE Murray, A TI Dynamics of Arterial Pressure Components in a Sheep Model of Hemorrhage SO 2014 COMPUTING IN CARDIOLOGY CONFERENCE (CINC), VOL 41 SE Computing in Cardiology Conference LA English DT Proceedings Paper CT 41st Computing in Cardiology Conference (CinC) CY SEP 07-10, 2014 CL Cambridge, MA SP Massachusetts Inst Technol, European Soc Cardiol, IEEE EMBS, Mortara, PhysioNet, Philips, Mindray, IBM, Zoll, Mitsubishi Elect, lOP Publishing, IMES, CSAIL, Medtronic, Boston Sci, Samsung, GE ID HEART-RATE RESPONSE AB There is a need for accurate monitors that can track blood loss and report a patient's current physiological response. We explored phase coherence between components of the arterial blood pressure waveform for this purpose. Adult conscious sheep underwent 25 mL/kgBody-weight hemorrhages over 15 minutes (14 total hemorrhage experiments) while continuous arterial blood pressure measurements were made. Phase coherence from a single arterial pressure monitor was assessed between all combinations of the pulse-pulse interval, systolic blood pressure, and pulse pressure sequences as a measure of the synchronization between the component dynamics. Phase coherence measures were compared during baseline, the peak compensatory response and a decompensation phase. Phase coherence in the range of 0.06 - 0.15 Hz between the pulse-pulse interval and systolic blood pressure sequences as well as the systolic blood pressure and pulse pressure sequences was elevated during the peak compensation period Analytical techniques to assess the relationship between signals recorded during hemorrhage can be explored for their potential predictive capabilities. C1 [Scully, Christopher G.; Strauss, David G.] US FDA, Div Biomed Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Kramer, George C.] Univ Texas Med Branch, Dept Anesthesiol, Galveston, TX 77555 USA. RP Scully, CG (reprint author), 10903 New Hampshire Ave Bldg 62 RM 1202C, Silver Spring, MD 20993 USA. EM christopher.scully@fda.hhs.gov NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2325-887X BN 978-1-4799-4346-3 J9 COMPUT CARDIOL CONF PY 2014 VL 41 BP 305 EP 308 PG 4 WC Cardiac & Cardiovascular Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology SC Cardiovascular System & Cardiology; Computer Science; Mathematical & Computational Biology GA BE2TW UT WOS:000370068300078 ER PT S AU Sassi, R Sparagino, L Stockbridge, NL Guadiana, JM Badilini, F AF Sassi, Roberto Sparagino, Luca Stockbridge, Norman L. Guadiana, Juan M. Badilini, Fabio BE Murray, A TI Proof of Concept for an International Long-Time Preservation ECG Format SO 2014 COMPUTING IN CARDIOLOGY CONFERENCE (CINC), VOL 41 SE Computing in Cardiology Conference LA English DT Proceedings Paper CT 41st Computing in Cardiology Conference (CinC) CY SEP 07-10, 2014 CL Cambridge, MA SP Massachusetts Inst Technol, European Soc Cardiol, IEEE EMBS, Mortara, PhysioNet, Philips, Mindray, IBM, Zoll, Mitsubishi Elect, lOP Publishing, IMES, CSAIL, Medtronic, Boston Sci, Samsung, GE AB We present a proof-of-concept of a medical data format for storing and retrieving 12-lead, 10-second standard electrocardiograms (ECG). The new format combines a digital ECG record into a standard graphical report (PDF). Using the very recent PDF/A-3 standard (ISO 19005-3: 2012), we designed a long-term preservation graphic report (such as a standard 3 x4 or 6x2 ECG printout) in which the original ECG digital data (using the aECG ANSI/HL7 R1-2004 format) is embedded as a compressed attachment. The proposal also includes two ways of ensuring conformity between the ECG vector images and the digital data. First, a digital signature is added to guarantee that the document was not modified after creation. Second, specific metadata are inserted to allow a direct digital comparison between the vector ECG printout and the data. To prove the feasibility of the approach, 93 aECGs, selected from different device manufacturers, resolutions and sample rates, were converted into the new format and then validated. Differences between digital data and vector graphics were always smaller than 0.02 mu V, significantly below the typical AID converter resolution. C1 [Sassi, Roberto; Sparagino, Luca] Univ Milan, Dipartimento Informat, Via Bramante 65, I-26013 Crema, CR, Italy. [Stockbridge, Norman L.] US FDA, Div Cardiovasc & Renal Prod, CDER, Silver Spring, MD USA. [Guadiana, Juan M.] FAA, Las Cruces, NM USA. [Badilini, Fabio] AMPS LLC, New York, NY USA. RP Sassi, R (reprint author), Univ Milan, Dipartimento Informat, Via Bramante 65, I-26013 Crema, CR, Italy. EM roberto.sassi@unimi.it RI Sassi, Roberto/B-8136-2008; Spargino, Luca/M-4435-2015 OI Sassi, Roberto/0000-0001-9729-2641; Spargino, Luca/0000-0003-4572-9252 NR 7 TC 1 Z9 1 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2325-887X BN 978-1-4799-4346-3 J9 COMPUT CARDIOL CONF PY 2014 VL 41 BP 461 EP 464 PG 4 WC Cardiac & Cardiovascular Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology SC Cardiovascular System & Cardiology; Computer Science; Mathematical & Computational Biology GA BE2TW UT WOS:000370068300117 ER PT S AU Chen, DD Gray, RA Fenton, FH AF Chen, Diandian Diana Gray, Richard A. Fenton, Flavio H. BE Murray, A TI Modelling the Take-off Voltage of the Action Potential during Fast Pacing SO 2014 COMPUTING IN CARDIOLOGY CONFERENCE (CINC), VOL 41 SE Computing in Cardiology Conference LA English DT Proceedings Paper CT 41st Computing in Cardiology Conference (CinC) CY SEP 07-10, 2014 CL Cambridge, MA SP Massachusetts Inst Technol, European Soc Cardiol, IEEE EMBS, Mortara, PhysioNet, Philips, Mindray, IBM, Zoll, Mitsubishi Elect, lOP Publishing, IMES, CSAIL, Medtronic, Boston Sci, Samsung, GE ID VENTRICULAR-FIBRILLATION AB To date over 50 models for cardiac action potential have been developed, and while they vary widely in their complexity and the physiological characteristics that they reproduce, most fail to accurately replicate the takeoff potential during fast pacing and fibrillation. A specific aspect we focus is on the takeoff potential for an S2 stimulation following a steady S1 action potential. In microelectrodes and optical mapping experiment, the take-off voltage of an S2 action potential has been shown to be relatively high while most cardiac cell models do not reflect this feature, as the voltage needs to return close to the resting membrane potential before it can be reactivated. Since this difference can have great effects in electrical waves and their dynamics during tachycardia and fibrillation, we developed a framework that can be incorporated into the models to reproduce. the experimentally observed higher take off potential. Recovery of inactivation in the Sodium current is the key to the activation from an S2 stimulus. Therefore, we focused on the sodium inactivation gates h and j. We hypothesized that the j gate is the source of the low take off potential because it recovers during AP final repolarization. Our procedure is to model the dynamics of both gates via a single one with an adjustable time constant tau. We model tau with an asymmetric equation. Using this equation form, we can manipulate the width, height, and asymptotic values of tau. The features that change the takeoff potential significantly are the midpoint and asymptotic valuers) of tau. By shifting the midpoint value of tau to a higher value, the takeoff potential increase, while rest of the sodium dynamics remains unaltered. C1 [Chen, Diandian Diana; Fenton, Flavio H.] Georgia Inst Technol, Sch Phys, 837 State St, Atlanta, GA 30332 USA. [Gray, Richard A.] US FDA, Silver Spring, MD USA. RP Chen, DD (reprint author), Georgia Inst Technol, Sch Phys, 837 State St, Atlanta, GA 30332 USA. EM dchen87@gatech.edu NR 12 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2325-887X BN 978-1-4799-4346-3 J9 COMPUT CARDIOL CONF PY 2014 VL 41 BP 685 EP 688 PG 4 WC Cardiac & Cardiovascular Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology SC Cardiovascular System & Cardiology; Computer Science; Mathematical & Computational Biology GA BE2TW UT WOS:000370068300173 ER PT S AU Calhoun, WR Ilev, I AF Calhoun, William R., III Ilev, Ilko GP IEEE TI Effect of Femtosecond Laser Pulse Energy and Repetition Rate on Laser Induced Second and Third Harmonic Generation in Corneal Tissue SO 2014 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY JUN 08-13, 2014 CL San Jose, CA ID LIGHT; SURGERY; RETINA AB We present a quantitative study on the effect of femtosecond laser pulse energy and repetition rate on the intensity and duration of the laser induced second and third harmonic generation in fresh corneal tissue. C1 [Calhoun, William R., III; Ilev, Ilko] US FDA, Opt Therapeut & Med Nanophoton Lab, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Calhoun, WR (reprint author), US FDA, Opt Therapeut & Med Nanophoton Lab, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM William.Calhoun@fda.hhs.gov NR 7 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 J9 CONF LASER ELECTR PY 2014 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BE2RC UT WOS:000369908600073 ER PT S AU Hassan, M Gaitan, B Ilev, I AF Hassan, Moinuddin Gaitan, Brandon Ilev, Ilko GP IEEE TI Decontamination of Medical Device Surface Using Ultrashort Pulsed Laser Irradiation SO 2014 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY JUN 08-13, 2014 CL San Jose, CA ID DISINFECTION AB We present a novel approach for non-contact, rapid and chemical-free decontamination of medical device surfaces using near-infrared ultrashort (nano-to femtosecond) pulse lasers. A proof-of-principal experimental platform is validated through multivariable comparison studies. C1 [Hassan, Moinuddin; Gaitan, Brandon; Ilev, Ilko] US FDA, Opt Therapeut & Med Nanophoton Lab, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Hassan, M (reprint author), US FDA, Opt Therapeut & Med Nanophoton Lab, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM moinuddin.hassan@fda.hhs.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 J9 CONF LASER ELECTR PY 2014 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BE2RC UT WOS:000369908600080 ER PT S AU Li, DW Zheng, JF Liu, Y Chen, J Pan, CW Kainz, W AF Li, Dawei Zheng, Jianfeng Liu, Yan Chen, Ji Pan, Changwan Kainz, Wolfgang GP IEEE TI Using Scaling Approach to Estimate MRI RF Field Induced Heating for Small Medical Implant SO 2014 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 AUG 03-08, 2014 CL Raleigh, NC SP IEEE, EMC Soc, ANDRO, ARRL, FEKO, GAUSS INSTRUMENTS, INFIELD Sci Inc, RETLIF TESTING LABS, ETS LINDGREN, ENR Seven Mountains Sci Inc, Evaluat Engn, IEEE Antennas & Propagat Magazine, IEEE Microwave Magazine, ATER, In Compliance Same Page Publishing Inc, ITEM Interference Technol, Microwave Journal, Safety & EMC Magazine, Webcom Commun Corp, Wireless Design & Dev, ECN DE RF induced heating; MRI safety; scaling approach; medical implants AB In this paper, a quick and efficient approach is proposed to estimate the in-vivo RF induced heating of small medical implants under MRI procedure. The method is based on scaling the in-vivo incident electric fields. Numerical and experimental studies demonstrate the efficiency and accuracy of the proposed method. C1 [Li, Dawei; Zheng, Jianfeng; Liu, Yan; Chen, Ji] Univ Houston, Dept Elect & Comp Engn, Houston, TX 77004 USA. [Pan, Changwan] Microtech Co Ltd, Nanjing, Jiangsu, Peoples R China. [Kainz, Wolfgang] US FDA, Rockville, MD 20857 USA. RP Li, DW (reprint author), Univ Houston, Dept Elect & Comp Engn, Houston, TX 77004 USA. EM dli15@central.uh.edu; jzheng3@central.uh.edu; jchen18@central.uh.edu; wolfgang.kainz@fda.hhs.gov NR 7 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 978-1-4799-5545-9 J9 IEEE INT SYMP ELEC PY 2014 BP 109 EP 112 PG 4 WC Engineering, Electrical & Electronic SC Engineering GA BG9OA UT WOS:000393471300020 ER PT S AU Huang, X Zheng, JF Chen, J Wu, X Kono, M Hozono, H Kainz, W AF Huang, Xin Zheng, Jianfeng Chen, Ji Wu, Xin Kono, Mari Hozono, Hideki Kainz, Wolfgang GP IEEE TI MRI Heating Reduction for External Fixation Devices Using Absorption Material SO 2014 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 AUG 03-08, 2014 CL Raleigh, NC SP IEEE, EMC Soc, ANDRO, ARRL, FEKO, GAUSS INSTRUMENTS, INFIELD Sci Inc, RETLIF TESTING LABS, ETS LINDGREN, ENR Seven Mountains Sci Inc, Evaluat Engn, IEEE Antennas & Propagat Magazine, IEEE Microwave Magazine, ATER, In Compliance Same Page Publishing Inc, ITEM Interference Technol, Microwave Journal, Safety & EMC Magazine, Webcom Commun Corp, Wireless Design & Dev, ECN DE absorption material; RF heating reduction; external fixation AB Using absorption materials to reduce RF heating during MRI procedure is studied in this paper. Materials with different electromagnetic absorption characteristics are used to alter the EM and current distributions on the device. Consequently, the RF induced heating behaviors of external fixation devices can be reduced. Numerical and experimental studies are provided to demonstrate the potentials of reducing the RF heating for external fixation devices of using lossy materials. C1 [Huang, Xin; Zheng, Jianfeng; Chen, Ji] Univ Houston, ECE Dept, Houston, TX 77004 USA. [Wu, Xin; Kono, Mari; Hozono, Hideki] Molex Inc, Lisle, IL USA. [Kainz, Wolfgang] US FDA, Silver Spring, MD USA. RP Huang, X (reprint author), Univ Houston, ECE Dept, Houston, TX 77004 USA. EM xhuang12@uh.edu; jchen18@uh.edu; wolfgang.kainz@fda.hhs.gov NR 5 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 978-1-4799-5545-9 J9 IEEE INT SYMP ELEC PY 2014 BP 113 EP 117 PG 5 WC Engineering, Electrical & Electronic SC Engineering GA BG9OA UT WOS:000393471300021 ER PT S AU Li, DW Huang, X Chen, J Kainz, W AF Li, Dawei Huang, Xin Chen, Ji Kainz, Wolfgang GP IEEE TI A Study of Antenna Efficiency and MRI Compatibility of Cardiac Stent SO 2014 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 AUG 03-08, 2014 CL Raleigh, NC SP IEEE, EMC Soc, ANDRO, ARRL, FEKO, GAUSS INSTRUMENTS, INFIELD Sci Inc, RETLIF TESTING LABS, ETS LINDGREN, ENR Seven Mountains Sci Inc, Evaluat Engn, IEEE Antennas & Propagat Magazine, IEEE Microwave Magazine, ATER, In Compliance Same Page Publishing Inc, ITEM Interference Technol, Microwave Journal, Safety & EMC Magazine, Webcom Commun Corp, Wireless Design & Dev, ECN DE Implantable stent implants; Radiation efficiency; Biomedical wireless communication; MRI Compatibility AB Implantable stents can be used as radiation antennas for wireless communication of cardiovascular health monitoring data. However, such stent can also lead to RF induced heating during MRI procedure. In this paper, we investigate the effect of different stent size on the antenna radiation performance as well as its RF induced heating during MRI procedure. Preliminary investigations show that longer stent typically yields to better radiation efficiency but suffers from higher temperature rises. C1 [Li, Dawei] Univ Houston, Dept Elect & Comp Engn, Houston, TX 77004 USA. [Kainz, Wolfgang] US FDA, Rockville, MD 20857 USA. RP Li, DW (reprint author), Univ Houston, Dept Elect & Comp Engn, Houston, TX 77004 USA. EM dli15@central.uh.edu; xhuang12@central.uh.edu; jchen18@central.uh.edu; wolfgang.kainz@fda.hhs.gov NR 9 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 978-1-4799-5545-9 J9 IEEE INT SYMP ELEC PY 2014 BP 165 EP 170 PG 6 WC Engineering, Electrical & Electronic SC Engineering GA BG9OA UT WOS:000393471300031 ER PT S AU Krauthamer, V AF Krauthamer, Victor GP IEEE TI Neuromodulation with Subthreshold Electrical Stimulation: Mechanisms, Safety, and Seeking Proof of Effectiveness SO 2014 IEEE SIGNAL PROCESSING IN MEDICINE AND BIOLOGY SYMPOSIUM (SPMB) SE IEEE Signal Processing in Medicine and Biology Symposium LA English DT Proceedings Paper CT IEEE Signal Processing in Medicine and Biology Symposium CY DEC 13-13, 2014 CL Philadelphia, PA SP Neural Engineering Data Consortium, The Inst of Elect and Elect Engineers (Region 2), Signal Proc Soc (Philadelphia Sect) C1 [Krauthamer, Victor] US FDA, Off Sci & Engn Labs, Div Biomed Phys, Rockville, MD 20857 USA. RP Krauthamer, V (reprint author), US FDA, Off Sci & Engn Labs, Div Biomed Phys, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2372-7241 BN 978-1-4799-8184-7 J9 IEEE SIG PROC MED PY 2014 PG 1 WC Engineering, Electrical & Electronic SC Engineering GA BF2IS UT WOS:000380471200002 ER PT J AU Neufeld, E Iacono, MI Akinnagbe, E Wolf, J Oikonomidis, IV Sharma, D Wilm, B Wyss, M Jakab, A Cohen, E Kuster, N Kainz, W Angelone, LM AF Neufeld, Esra Iacono, Maria I. Akinnagbe, Esther Wolf, Johanna Oikonomidis, Ioannis V. Sharma, Deepika Wilm, Bertram Wyss, Michael Jakab, Andras Cohen, Ethan Kuster, Niels Kainz, Wolfgang Angelone, Leonardo M. GP IEEE TI Computational Platform Combining Detailed and Precise Functionalized Anatomical Phantoms with EM-Neuron Interaction Modeling SO 2014 XXXITH URSI GENERAL ASSEMBLY AND SCIENTIFIC SYMPOSIUM (URSI GASS) LA English DT Proceedings Paper CT 29th URSI General Assembly and Scientific Symposium (URSI GASS) CY AUG 16-23, 2014 CL Beijing, PEOPLES R CHINA SP URSI AB A computational framework including functionalized anatomical phantoms able to simulate electromagnetic (EM)-neuron interactions in complex tissue-structure environments was developed. The anatomic head model distinguishes a large number of structures, particularly in regions relevant to EM-neuron interactions (i.e., ear, eye, deep brain structures). Multimodal Magnetic Resonance (MR) images were acquired together with Diffusion Tensor Imaging (DTI) data to guide neuron model placement and inform about tissue anisotropy. A dedicated EM solver was implemented and coupled with dynamic models of neuronal activity. The topologically conforming, non-self-intersecting, high-element-quality surfaces are suitable for a wide range of numerical methods and solvers, as demonstrated in an application derived from transcranial alternating current stimulation. The platform was validated against literature data, e.g., on the SENN [1] model which was further extended to account for local thermal effects. Additionally, the EM-neuron coupling simulation platform was also applied to investigate MRI gradient coil switching induced nerve stimulation. C1 [Neufeld, Esra; Oikonomidis, Ioannis V.; Sharma, Deepika; Kuster, Niels] Fdn Res Informat Technol Soc ITIS, CH-8004 Zurich, Switzerland. [Iacono, Maria I.; Akinnagbe, Esther; Cohen, Ethan; Kainz, Wolfgang; Angelone, Leonardo M.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Wolf, Johanna; Oikonomidis, Ioannis V.; Sharma, Deepika; Kuster, Niels] ETH, Swiss Fed Inst Technol, CH-8092 Zurich, Switzerland. [Wilm, Bertram; Wyss, Michael] Univ Zurich, Inst Biomed Engn, CH-8006 Zurich, Switzerland. [Wilm, Bertram; Wyss, Michael] Swiss Fed Inst Technol, Zurich, Switzerland. [Jakab, Andras] Med Univ Vienna, Computat Image Anal & Radiol Lab, A-1090 Vienna, Austria. RP Neufeld, E (reprint author), Fdn Res Informat Technol Soc ITIS, CH-8004 Zurich, Switzerland. EM neufeld@itis.ethz.ch; maria.iacono@gmail.com; akinnesther@gmail.com; wolf@itis.ethz.ch; ioannis@itis.ethz.ch; sharma@itis.ethz.ch; wilm@biomed.ee.ethz.ch; wyss@biomed.ee.ethz.ch; andras.jakab@meduniwien.ac.at; ethan.cohen@fda.hhs.gov; kuster@itis.ethz.ch; wolfgang.kainz@fda.hhs.gov; leonardo.angelone@fda.hhs.gov NR 7 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4673-5225-3 PY 2014 PG 4 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BE0QU UT WOS:000366628703301 ER PT J AU Ghosh, T AF Ghosh, T. BE Chilcott, R Brain, K TI SYSTEMIC TOPICAL DRUG DELIVERY: US REGULATORY PERSPECTIVES ON PRODUCT DEVELOPMENT, BIOPHARMACEUTICALS AND CLINICAL PHARMACOLOGY SO ADVANCES IN DERMATOLOGICAL SCIENCES SE Issues in Toxicology LA English DT Article; Book Chapter C1 [Ghosh, T.] US FDA, Off New Drugs & Qual Assessment, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Ghosh, T (reprint author), US FDA, Off New Drugs & Qual Assessment, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND BN 978-1-84973-463-9 J9 ISSUES TOXICOL PY 2014 VL 20 BP 287 EP 307 PG 21 WC Dermatology; Toxicology SC Dermatology; Toxicology GA BG3WO UT WOS:000388324400025 ER PT J AU Glindmeyer, HW Harry, A AF Glindmeyer, H. W. Harry, A. TI Fda's Current Approach To Premarket Notification SuBMIssions (510(k)s) For Continuous Positive Pressure Ventilators SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Glindmeyer, H. W.] US FDA, Silver Spring, MD USA. [Glindmeyer, H. W.; Harry, A.] US FDA, White Oak, DC USA. EM henry.glindmeyer@fda.hhs.gov 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 2014 VL 189 MA A4578 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204072 ER PT J AU Wang, Y Pereira, C Scott, DE Brantly, M Rouhani, F Reed, JL AF Wang, Y. Pereira, C. Scott, D. E. Brantly, M. Rouhani, F. Reed, J. L. TI Cytosolic Alpha-1 Proteinase Inhibitor Regulates Mitochondrial Superoxide Generation And Inflammasome Signaling In Monocytes: Role Of Autophagy SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Wang, Y.; Pereira, C.; Scott, D. E.; Reed, J. L.] US FDA, Bethesda, MD 20014 USA. [Brantly, M.; Rouhani, F.] Univ Florida, Gainesville, FL USA. 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 2014 VL 189 MA A4942 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204434 ER PT J AU Wang, MY Misakian, M He, HJ Bajcsy, P Abbasi, F Davis, JM Cole, KD Turko, IV Wang, LL AF Wang, Meiyao Misakian, Martin He, Hua-Jun Bajcsy, Peter Abbasi, Fatima Davis, Jeffrey M. Cole, Kenneth D. Turko, Illarion V. Wang, Lili TI Quantifying CD4 receptor protein in two human CD4+lymphocyte preparations for quantitative flow cytometry SO CLINICAL PROTEOMICS LA English DT Article DE Cryopreserved peripheral blood mononuclear cells (PBMC); Lyophilized Cyto-Trol (TM); CD4 receptor density; Flow cytometry; Multiple reaction monitoring (MRM) mass spectrometry (MS); Scanning electron microscopy (SEM); Microvilli; Cell surface area AB Background: In our previous study that characterized different human CD4+ lymphocyte preparations, it was found that both commercially available cryopreserved peripheral blood mononuclear cells (PBMC) and a commercially available lyophilized PBMC (Cyto-Trol T) preparation fulfilled a set of criteria for serving as biological calibrators for quantitative flow cytometry. However, the biomarker CD4 protein expression level measured for T helper cells from Cyto-Trol was about 16% lower than those for cryopreserved PBMC and fresh whole blood using flow cytometry and mass cytometry. A primary reason was hypothesized to be due to steric interference in anti-CD4 antibody binding to the smaller sized lyophilized control cells. Method: Targeted multiple reaction monitoring (MRM) mass spectrometry (MS) is used to quantify the copy number of CD4 receptor protein per CD4+ lymphocyte. Scanning electron microscopy (SEM) is utilized to assist searching the underlying reasons for the observed difference in CD4 receptor copy number per cell determined by MRM MS and CD4 expression measured previously by flow cytometry. Results: The copy number of CD4 receptor proteins on the surface of the CD4+ lymphocyte in cryopreserved PBMCs and in lyophilized control cells is determined to be (1.45 +/- 0.09) x 10(5) and (0.85 +/- 0.11) x 10(5), respectively, averaged over four signature peptides using MRM MS. In comparison with cryopreserved PBMCs, there are more variations in the CD4 copy number in lyophilized control cells determined based on each signature peptide. SEM images of CD4+ lymphocytes from lyophilized control cells are very different when compared to the CD4+ T cells from whole blood and cryopreserved PBMC. Conclusion: Because of the lyophilization process applied to Cyto-Trol control cells, a lower CD4 density value, defined as the copy number of CD4 receptors per CD4+ lymphocyte, averaged over three different production lots is most likely explained by the loss of the CD4 receptors on damaged and/or broken microvilli where CD4 receptors reside. Steric hindrance of antibody binding and the association of CD4 receptors with other biomolecules likely contribute significantly to the nearly 50% lower CD4 receptor density value for cryopreserved PBMC determined from flow cytometry compared to the value obtained from MRM MS. C1 [Wang, Meiyao; Turko, Illarion V.] Univ Maryland, Inst Biosci & Biotechnol Res, 9600 Gudelsky Dr, Rockville, MD 20850 USA. [Wang, Meiyao; Turko, Illarion V.] NIST, Biomol Measurement Div, Gaithersburg, MD 20899 USA. [Misakian, Martin] NIST, Quantum Measurements Div, Gaithersburg, MD 20899 USA. [He, Hua-Jun; Cole, Kenneth D.; Wang, Lili] NIST, Biosyst & Biomat Div, Gaithersburg, MD 20899 USA. [Bajcsy, Peter] NIST, Software & Syst Div, Gaithersburg, MD 20899 USA. [Abbasi, Fatima] CBER FDA, Lab Stem Cell Biol, Cellular & Tissue Therapy Branch, Div Cell & Gene Therapies, Bethesda, MD 20892 USA. [Davis, Jeffrey M.] NIST, Mat Measurement Sci Div, Gaithersburg, MD 20899 USA. RP Wang, MY (reprint author), Univ Maryland, Inst Biosci & Biotechnol Res, 9600 Gudelsky Dr, Rockville, MD 20850 USA. EM meiyaow@umd.edu; lili.wang@nist.gov NR 23 TC 2 Z9 2 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1542-6416 EI 1559-0275 J9 CLIN PROTEOM JI Clin. Proteom. PY 2014 VL 11 AR 43 DI 10.1186/1559-0275-11-43 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA V42YR UT WOS:000209649600038 PM 25593565 ER PT S AU Delmonte, P Fardin-Kia, AR Aldai, N Mossoba, MM Kramer, JKG AF Delmonte, Pierluigi Fardin-Kia, Ali Reza Aldai, Noelia Mossoba, Magdi M. Kramer, John K. G. BE Sels, B Philippaerts, A TI Analysis of Conjugated and Other Fatty Acids SO CONJUGATED LINOLEIC ACIDS AND CONJUGATED VEGETABLE OILS SE RSC Catalysis Series LA English DT Article; Book Chapter ID PERFORMANCE LIQUID-CHROMATOGRAPHY; TRANS-PALMITOLEIC ACID; ALPHA-ELEOSTEARIC ACID; SILVER-ION HPLC; LINOLEIC-ACID; MILK-FAT; GAS-CHROMATOGRAPHY; CLA ISOMERS; OCTADECADIENOIC ACID; STATIONARY PHASES C1 [Delmonte, Pierluigi; Fardin-Kia, Ali Reza; Mossoba, Magdi M.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. [Aldai, Noelia] Univ Basque Country UPV EHU, Fac Pharm, Dept Pharm & Food Sci, Vitoria 01006, Spain. [Kramer, John K. G.] Agr & Agri Food Canada, Guelph Food Res Ctr, Guelph, ON, Canada. RP Delmonte, P (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Pierluigi.Delmonte@fda.hhs.gov; jkgkramer@rogers.com NR 117 TC 0 Z9 0 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 1757-6725 BN 978-1-78262-021-1; 978-1-84973-900-9 J9 RSC CATAL SER PY 2014 IS 19 BP 172 EP 231 D2 10.1039/9781782620211 PG 60 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA BG3PG UT WOS:000388104100009 ER PT S AU Weaver, JD Gupta, S Woods, TO AF Weaver, Jason D. Gupta, Shikha Woods, Terry O. BE Mitchell, MR Smith, SW Woods, T Berg, BT TI The Effects of Test Speed on Fatigue Life of Nitinol Wire in Rotary Bend SO FATIGUE AND FRACTURE OF MEDICAL METALLIC MATERIALS AND DEVICES: 3RD VOLUME SE American Society for Testing and Materials Special Technical Publications LA English DT Proceedings Paper CT Symposium on Fatigue and Fracture of Medical Metallic Materials and Devices CY NOV 14, 2012 CL Atlanta, GA SP ASTM Int Comm E08 Fatigue & Fracture, ASTM Subcommittee E08 05 Cycl Deformat & Fatigue Crack Format DE fatigue; nitinol; speed; frequency; rotary bend; wire ID SHAPE-MEMORY WIRES; FRACTURE; PREVALENCE; ROTATION; STENTS AB In order to acquire durability data for medical devices in a reasonable amount of time, manufacturers often perform fatigue testing at an accelerated rate. However, the effects of increasing test frequency on the fatigue life of nitinol devices have not been thoroughly investigated. In order to better understand how test speed affects nitinol fatigue, superelastic nitinol wire was tested in body-temperature water in a free (unguided) rotary bend fatigue apparatus. Alternating strains of 0.9 %, 1.0 %, 1.1 %, 1.5 %, or 2.0 % were applied at rotational test speeds of 0.6, 6, or 60 Hz. Except for the highest strain level, results trended toward increased fatigue life at higher test frequencies. Fatigue life at 6 and 60 Hz was significantly greater (p< 0.05) than fatigue life at the slowest test speed for alternating strains of 1.0 %, 1.1 %, and 1.5 %. High-speed video of 1.0 % and 1.1 % alternating strain tests at 60 Hz revealed small vibrations that manifested as side-to-side rocking motion of the wire. Because of the unexpected vibrations seen in nitinol wire tests, supplementary testing of cobalt-chromium wire was conducted. Highspeed video of cobalt-chromium wire at 0.5 % alternating strain and 333 Hz test speed showed a vertical bouncing motion that appeared to be a second vibration mode. To constrain motion and reduce vibration effects, wire guides were constructed and used in additional testing. Guided tests of cobalt-chromium wire showed reduced vibration, resulting in a lowered fatigue life that was nearer to values expected based on literature. Although further testing is needed, vibrations appear to artificially increase fatigue life by altering the imposed radius of curvature and reducing the amount of strain wires undergo in each cycle. Rotary bend wire fatigue testing remains a relatively simple and useful test; however, caution is recommended when the test is conducted without wire guides, as vibrations may affect fatigue life. C1 [Weaver, Jason D.; Gupta, Shikha; Woods, Terry O.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Weaver, JD (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM jason.weaver@fda.hhs.gov NR 15 TC 0 Z9 0 U1 0 U2 0 PU ASTM INTERNATIONAL PI WEST CONSHOHOCKEN PA 100 BARR HARBOR DRIVE, PO BOX C700, WEST CONSHOHOCKEN, PA 19428-2959 USA SN 0066-0558 BN 978-0-8031-7545-7 J9 AM SOC TEST MATER PY 2014 VL 1559 BP 1 EP 17 DI 10.1520/STP155920120213 PG 17 WC Materials Science, Biomaterials; Materials Science, Characterization & Testing SC Materials Science GA BE3OB UT WOS:000371052500002 ER PT J AU Liu, SL Paule, MG Zhang, X Newport, GD Patterson, TA Apana, SM Berridge, MS Maisha, MP Slikker, W Wang, C AF Liu, Shuliang Paule, Merle G. Zhang, Xuan Newport, Glenn D. Patterson, Tucker A. Apana, Scott M. Berridge, Marc S. Maisha, Mackean P. Slikker, William, Jr. Wang, Cheng TI Positron emission tomography with [F-18]FLT revealed sevoflurane-induced inhibition of neural progenitor cell expansion in vivo SO FRONTIERS IN NEUROLOGY LA English DT Article DE neural progenitor cell; positron emission tomography; [F-18]FLT; sevoflurane; proliferation AB Neural progenitor cell expansion is critical for normal brain development and an appropriate response to injury. During the brain growth spurt, exposures to general anesthetics, which either block the N-methyl-D-aspartate receptor or enhance the gamma-aminobutyric acid receptor type A can disturb neuronal transduction. This effect can be detrimental to brain development. Until now, the effects of anesthetic exposure on neural progenitor cell expansion in vivo had seldom been reported. Here, minimally invasive micro positron emission tomography (microPET) coupled with 3'-deoxy-3' [F-18] fluoro-l-thymidine ([F-18]FLT) was utilized to assess the effects of sevoflurane exposure on neural progenitor cell proliferation. ELT, a thymidine analog, is taken up by proliferating cells and phosphorylated in the cytoplasm, leading to its intracellular trapping. Intracellular retention of [F-18]FLT, thus, represents an observable in vivo marker of cell proliferation. Here, postnatal day 7 rats (n = 11/group) were exposed to 2.5% sevoflurane or room air for 9 h. For up to 2 weeks following the exposure, standard uptake values (SUVs) for [F-18]-FLT in the hippocampal formation were significantly attenuated in the sevoflurane-exposed rats (p < 0.0001), suggesting decreased uptake and retention of [F-18]FLT (decreased proliferation) in these regions. Four weeks following exposure, SUVs for [F-18]FLT were comparable in the sevoflurane-exposed rats and in controls. Co-administration of 7-nitroindazole (30 mg/kg, n= 5), a selective inhibitor of neuronal nitric oxide synthase, significantly attenuated the SUVs for [F-18]FLT in both the air-exposed (p = 0.00006) and sevoflurane-exposed rats (p = 0.0427) in the first week following the exposure. These findings suggested that microPET in couple with [F-18]FLT as cell proliferation marker could be used as a non-invasive modality to monitor the sevoflurane-induced inhibition of neural progenitor cell proliferation in vivo. C1 [Liu, Shuliang; Paule, Merle G.; Zhang, Xuan; Newport, Glenn D.; Patterson, Tucker A.; Slikker, William, Jr.; Wang, Cheng] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Apana, Scott M.; Berridge, Marc S.] 3D Imaging LLC, Little Rock, AR USA. [Maisha, Mackean P.] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Wang, C (reprint author), US FDA, Natl Ctr Toxicol Res, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Cheng.wang@fda.hhs.gov NR 65 TC 1 Z9 1 U1 0 U2 1 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-2295 J9 FRONT NEUROL JI Front. Neurol. PY 2014 VL 5 AR 234 DI 10.3389/fneur.2014.00234 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V42QW UT WOS:000209629300220 PM 25452743 ER PT J AU McCune, SK Mulugeta, YA AF McCune, Susan K. Mulugeta, Yeruk Ager TI Regulatory science needs for neonates: a call for neonatal community collaboration and innovation SO FRONTIERS IN PEDIATRICS LA English DT Editorial Material DE neonatal; regulatory science; drugs; trials; collaboration C1 [McCune, Susan K.; Mulugeta, Yeruk Ager] US FDA, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Mulugeta, Yeruk Ager] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP McCune, SK (reprint author), US FDA, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM susan.mccune@fda.hhs.gov NR 16 TC 4 Z9 5 U1 0 U2 0 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 2296-2360 J9 FRONT PEDIATR JI Front. Pediatr. PY 2014 VL 2 AR 135 DI 10.3389/fped.2014.00135 PG 3 WC Pediatrics SC Pediatrics GA V46PX UT WOS:000209897200133 PM 25520945 ER PT J AU Su, ZQ Fang, H Hong, HX Shi, LM Zhang, WQ Zhang, WW Zhang, YY Dong, ZR Lancashire, LJ Bessarabova, M Yang, X Ning, BT Gong, BS Meehan, J Xu, J Ge, WG Perkins, R Fischer, M Tong, W AF Su, Zhenqiang Fang, Hong Hong, Huixiao Shi, Leming Zhang, Wenqian Zhang, Wenwei Zhang, Yanyan Dong, Zirui Lancashire, Lee J. Bessarabova, Marina Yang, Xi Ning, Baitang Gong, Binsheng Meehan, Joe Xu, Joshua Ge, Weigong Perkins, Roger Fischer, Matthias Tong, Weida TI An investigation of biomarkers derived from legacy microarray data for their utility in the RNA-seq era SO GENOME BIOLOGY LA English DT Article ID GENE-EXPRESSION SIGNATURE; MULTIPLE-MYELOMA; CONNECTIVITY MAP; REPRODUCIBILITY; CONSISTENCY; PLATFORMS; MODELS AB Background: Gene expression microarray has been the primary biomarker platform ubiquitously applied in biomedical research, resulting in enormous data, predictive models, and biomarkers accrued. Recently, RNA-seq has looked likely to replace microarrays, but there will be a period where both technologies co-exist. This raises two important questions: Can microarray-based models and biomarkers be directly applied to RNA-seq data? Can future RNA-seq-based predictive models and biomarkers be applied to microarray data to leverage past investment? Results: We systematically evaluated the transferability of predictive models and signature genes between microarray and RNA-seq using two large clinical data sets. The complexity of cross-platform sequence correspondence was considered in the analysis and examined using three human and two rat data sets, and three levels of mapping complexity were revealed. Three algorithms representing different modeling complexity were applied to the three levels of mappings for each of the eight binary endpoints and Cox regression was used to model survival times with expression data. In total, 240,096 predictive models were examined. Conclusions: Signature genes of predictive models are reciprocally transferable between microarray and RNA-seq data for model development, and microarray-based models can accurately predict RNA-seq-profiled samples; while RNA-seq-based models are less accurate in predicting microarray-profiled samples and are affected both by the choice of modeling algorithm and the gene mapping complexity. The results suggest continued usefulness of legacy microarray data and established microarray biomarkers and predictive models in the forthcoming RNA-seq era. C1 [Su, Zhenqiang; Fang, Hong; Hong, Huixiao; Zhang, Wenqian; Yang, Xi; Ning, Baitang; Gong, Binsheng; Meehan, Joe; Xu, Joshua; Ge, Weigong; Perkins, Roger; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Su, Zhenqiang; Bessarabova, Marina] Thomson Reuters, IP & Sci, Boston, MA 02210 USA. [Shi, Leming; Lancashire, Lee J.] Fudan Univ, Sch Life Sci & Pharm, State Key Lab Genet Engn, Shanghai 201203, Peoples R China. [Shi, Leming] Fudan Univ, Sch Life Sci & Pharm, MOE Key Lab Contemporary Anthropol, Shanghai 201203, Peoples R China. [Shi, Leming] Fudan Zhangjiang Ctr Clin Genom, Shanghai 201203, Peoples R China. [Shi, Leming; Zhang, Wenwei] Zhanjiang Ctr Translat Med, Shanghai 201203, Peoples R China. [Zhang, Wenwei; Zhang, Yanyan; Dong, Zirui] BGI Shenzhen, Guangdong 518083, Peoples R China. [Dong, Zirui; Fischer, Matthias] Univ Childrens Hosp Cologne, Dept Pediat Oncol & Hematol, D-50924 Cologne, Germany. [Fischer, Matthias] Univ Childrens Hosp Cologne, Ctr Mol Med CMMC, D-50924 Cologne, Germany. RP Su, ZQ (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM zhenqiangsu@gmail.com; matthias.fischer@uk-koeln.de; weida.tong@fda.hhs.gov RI Gong, Binsheng/E-2306-2015 OI Gong, Binsheng/0000-0002-8724-5435 FU National Science Foundation of China [31471239]; National High Technology Research and Development Program of China [2015AA020104] FX The authors gratefully acknowledge the contribution of Drs Jean Thierry-Mieg,Danielle Thierry-Mieg, Stan Gaj, Marc o Chierici, and their co-workers for processing the RNA-Seq data in the FDA SEQC Toxicogenomic data set using their respective data analysis pipelines. This work was supported in part by the National High Technology Research and Development Program of China (2015AA020104, to LS) and the National Science Foundation of China (31471239, to LS). NR 30 TC 8 Z9 8 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2014 VL 15 IS 12 AR 523 DI 10.1186/s13059-014-0523-y PG 26 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AW9XX UT WOS:000346609500034 PM 25633159 ER PT J AU Gong, BS Wang, C Su, ZQ Hong, HX Thierry-Mieg, J Thierry-Mieg, D Shi, LM Auerbach, SS Tong, WD Xu, J AF Gong, Binsheng Wang, Charles Su, Zhenqiang Hong, Huixiao Thierry-Mieg, Jean Thierry-Mieg, Danielle Shi, Leming Auerbach, Scott S. Tong, Weida Xu, Joshua TI Transcriptomic profiling of rat liver samples in a comprehensive study design by RNA-Seq SO SCIENTIFIC DATA LA English DT Article AB RNA-Seq provides the capability to characterize the entire transcriptome in multiple levels including gene expression, allele specific expression, alternative splicing, fusion gene detection, and etc. The US FDA-led SEQC (i.e., MAQC-III) project conducted a comprehensive study focused on the transcriptome profiling of rat liver samples treated with 27 chemicals to evaluate the utility of RNA-Seq in safety assessment and toxicity mechanism elucidation. The chemicals represented multiple chemogenomic modes of action (MOA) and exhibited varying degrees of transcriptional response. The paired-end 100 bp sequencing data were generated using Illumina HiScanSQ and/or HiSeq 2000. In addition to the core study, six animals (i.e., three aflatoxin B1 treated rats and three vehicle control rats) were sequenced three times, with two separate library preparations on two sequencing machines. This large toxicogenomics dataset can serve as a resource to characterize various aspects of transcriptomic changes (e.g., alternative splicing) that are byproduct of chemical perturbation. C1 [Gong, Binsheng; Su, Zhenqiang; Hong, Huixiao; Shi, Leming; Tong, Weida; Xu, Joshua] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Wang, Charles] Loma Linda Univ, Sch Med, Ctr Genom, Loma Linda, CA 92350 USA. [Wang, Charles] Loma Linda Univ, Sch Med, Div Microbiol & Mol Genet, Loma Linda, CA 92350 USA. [Thierry-Mieg, Jean; Thierry-Mieg, Danielle] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20814 USA. [Shi, Leming] Fudan Univ, State Key Lab Genet Engn, Shanghai 201203, Peoples R China. [Shi, Leming] Fudan Univ, MOE Key Lab Contemporary Anthropol, Sch Life Sci, Shanghai 201203, Peoples R China. [Shi, Leming] Fudan Univ, MOE Key Lab Contemporary Anthropol, Sch Pharm, Shanghai 201203, Peoples R China. [Auerbach, Scott S.] NIEHS, Biomol Screening Branch, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. RP Auerbach, SS (reprint author), NIEHS, Biomol Screening Branch, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. EM auerbachs@niehs.nih.gov; weida.tong@fda.hhs.gov; zhihua.xu@fda.hhs.gov RI THIERRY-MIEG, Jean/F-1975-2017 OI THIERRY-MIEG, Jean/0000-0002-0396-6789 FU Intramural Research Program of the NIH, National Library of Medicine FX This dataset was generated for the SEQC toxicogenomics study and the related research manuscript8. The authors would like to thank Philippe Rocca-Serra for his guidance and assistance in sample metadata collection and coding with ISA-TAB. This research was supported in part by the Intramural Research Program of the NIH, National Library of Medicine. The views presented in this article do not necessarily reflect current or future opinion or policy of the US Food and Drug Administration. Any mention of commercial products is for clarification and not intended as an endorsement. NR 24 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2052-4463 J9 SCI DATA JI Sci. Data PY 2014 VL 1 AR 140021 DI 10.1038/sdata.2014.21 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V45VG UT WOS:000209843500014 ER PT J AU Harpaz, R Odgers, D Gaskin, G DuMouchel, W Winnenburg, R Bodenreider, O Ripple, A Szarfman, A Sorbello, A Horvitz, E White, RW Shah, NH AF Harpaz, Rave Odgers, David Gaskin, Greg DuMouchel, William Winnenburg, Rainer Bodenreider, Olivier Ripple, Anna Szarfman, Ana Sorbello, Alfred Horvitz, Eric White, Ryen W. Shah, Nigam H. TI A time-indexed reference standard of adverse drug reactions SO SCIENTIFIC DATA LA English DT Article AB Undetected adverse drug reactions (ADRs) pose a major burden on the health system. Data mining methodologies designed to identify signals of novel ADRs are of deep importance for drug safety surveillance. The development and evaluation of these methodologies requires proper reference benchmarks. While progress has recently been made in developing such benchmarks, our understanding of the performance characteristics of the data mining methodologies is limited because existing benchmarks do not support prospective performance evaluations. We address this shortcoming by providing a reference standard to support prospective performance evaluations. The reference standard was systematically curated from drug labeling revisions, such as new warnings, which were issued and communicated by the US Food and Drug Administration in 2013. The reference standard includes 62 positive test cases and 75 negative controls, and covers 44 drugs and 38 events. We provide usage guidance and empirical support for the reference standard by applying it to analyze two data sources commonly mined for drug safety surveillance. C1 [Harpaz, Rave; Odgers, David; Gaskin, Greg; Shah, Nigam H.] Stanford Univ, Ctr Biomed Informat Res, Stanford, CA 94305 USA. [DuMouchel, William] Oracle Hlth Sci, Bedford, MA 01730 USA. [Winnenburg, Rainer; Bodenreider, Olivier; Ripple, Anna] NIH, Natl Lib Med, Bethesda, MD 20894 USA. [Szarfman, Ana; Sorbello, Alfred] US FDA, Silver Spring, MD 20993 USA. [Horvitz, Eric; White, Ryen W.] Microsoft Res, Redmond, WA 98052 USA. RP Harpaz, R (reprint author), Stanford Univ, Ctr Biomed Informat Res, Stanford, CA 94305 USA. EM rharpaz@stanford.edu FU NIH [U54-HG004028]; NIGMS [GM101430- 01A1]; Med Scholars fellowship from the Stanford School of Medicine; Intramural Research Program of the NIH, National Library of Medicine; Microsoft Research FX R.H. and N.H.S. acknowledge support by NIH grant U54-HG004028 for the National Center for Biomedical Ontology and by NIGMS grant GM101430- 01A1. D.O. acknowledges support by NIGMS grant GM101430- 01A1. G.G. is supported by a Med Scholars fellowship from the Stanford School of Medicine. This work was supported in part by the Intramural Research Program of the NIH, National Library of Medicine, and Microsoft Research. NR 29 TC 6 Z9 6 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2052-4463 J9 SCI DATA JI Sci. Data PY 2014 VL 1 AR 140043 DI 10.1038/sdata.2014.43 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V45VG UT WOS:000209843500039 ER PT J AU Xu, J Su, ZQ Hong, HX Thierry-Mieg, J Thierry-Mieg, D Kreil, DP Mason, CE Tong, WD Shi, LM AF Xu, Joshua Su, Zhenqiang Hong, Huixiao Thierry-Mieg, Jean Thierry-Mieg, Danielle Kreil, David P. Mason, Christopher E. Tong, Weida Shi, Leming TI Cross-platform ultradeep transcriptomic profiling of human reference RNA samples by RNA-Seq SO SCIENTIFIC DATA LA English DT Article AB Whole-transcriptome sequencing ('RNA-Seq') has been drastically changing the scale and scope of genomic research. In order to fully understand the power and limitations of this technology, the US Food and Drug Administration (FDA) launched the third phase of the MicroArray Quality Control (MAQC-III) project, also known as the SEquencing Quality Control (SEQC) project. Using two well-established human reference RNA samples from the first phase of the MAQC project, three sequencing platforms were tested across more than ten sites with built-in truths including spike-in of external RNA controls (ERCC), titration data and qPCR verification. The SEQC project generated over 30 billion sequence reads representing the largest RNA-Seq data ever generated by a single project on individual RNA samples. This extraordinarily ultradeep transcriptomic data set and the known truths built into the study design provide many opportunities for further research and development to advance the improvement and application of RNA-Seq. C1 [Xu, Joshua; Su, Zhenqiang; Hong, Huixiao; Tong, Weida; Shi, Leming] US FDA, Div Bioinformat cs & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Thierry-Mieg, Jean; Thierry-Mieg, Danielle] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20814 USA. [Kreil, David P.] Boku Univ Vienna, Chair Bioinformat Res Grp, Vienna, Austria. [Kreil, David P.] Univ Warwick, Coventry CV4 7AL, W Midlands, England. [Mason, Christopher E.] Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA. [Mason, Christopher E.] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY 10021 USA. [Shi, Leming] Fudan Univ, State Key Lab Genet Engn, Shanghai 201203, Peoples R China. [Shi, Leming] Fudan Univ, MOE Key Lab Contemporary Anthropol, Sch Life Sci, Shanghai 201203, Peoples R China. [Shi, Leming] Fudan Univ, MOE Key Lab Contemporary Anthropol, Sch Pharm, Shanghai 201203, Peoples R China. RP Tong, W (reprint author), US FDA, Div Bioinformat cs & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM leming.shi@gmail.com RI THIERRY-MIEG, Jean/F-1975-2017 OI THIERRY-MIEG, Jean/0000-0002-0396-6789 FU Intramural Research Program of the NIH, National Library of Medicine FX The authors would like to acknowledge all the participants of the SEQC project, particularly the sequencing sites for generating the high-quality data set. This research was supported in part by the Intramural Research Program of the NIH, National Library of Medicine. The views presented in this article do not necessarily reflect current or future opinion or policy of the US Food and Drug Administration. Any mention of commercial products is for clarification and not intended as an endorsement. NR 22 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2052-4463 J9 SCI DATA JI Sci. Data PY 2014 VL 1 AR 140020 DI 10.1038/sdata.2014.20 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V45VG UT WOS:000209843500013 ER PT J AU Yu, Y Zhao, C Su, ZQ Wang, C Fuscoe, JC Tong, WD Shi, LM AF Yu, Ying Zhao, Chen Su, Zhenqiang Wang, Charles Fuscoe, James C. Tong, Weida Shi, Leming TI Comprehensive RNA-Seq transcriptomic profiling across 11 organs, 4 ages, and 2 sexes of Fischer 344 rats SO SCIENTIFIC DATA LA English DT Article AB The rat is used extensively by the pharmaceutical, regulatory, and academic communities for safety assessment of drugs and chemicals and for studying human diseases; however, its transcriptome has not been well studied. As part of the SEQC (i.e., MAQC-III) consortium efforts, a comprehensive RNA-Seq data set was constructed using 320 RNA samples isolated from 10 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four ages (2-, 6-, 21-, and 104-week-old) with four biological replicates for each of the 80 sample groups (organ-sex- age). With the Ribo-Zero rRNA removal and Illumina RNA-Seq protocols, 41 million 50 bp single-end reads were generated per sample, yielding a total of 13.4 billion reads. This data set could be used to identify and validate new rat genes and transcripts, develop a more comprehensive rat transcriptome annotation system, identify novel gene regulatory networks related to tissue specific gene expression and development, and discover genes responsible for disease and drug toxicity and efficacy. C1 [Yu, Ying; Zhao, Chen; Shi, Leming] Fudan Univ, Ctr Pharmacogen, State Key Lab Genet Engn, Shanghai 201203, Peoples R China. [Yu, Ying; Zhao, Chen; Shi, Leming] Fudan Univ, MOE Key Lab Contemporary Anthropol, Sch Life Sci, Shanghai 201203, Peoples R China. [Yu, Ying; Zhao, Chen; Shi, Leming] Fudan Univ, MOE Key Lab Contemporary Anthropol, Sch Pharm, Shanghai 201203, Peoples R China. [Su, Zhenqiang; Fuscoe, James C.; Tong, Weida; Shi, Leming] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Wang, Charles] Loma Linda Univ, Sch Med, Ctr Genom, Loma Linda, CA 92350 USA. [Wang, Charles] Loma Linda Univ, Sch Med, Div Microbiol & Mol Genet, Loma Linda, CA 92350 USA. [Shi, Leming] Fudan Zhangjiang Ctr Clin Genom, Shanghai 201203, Peoples R China. [Shi, Leming] Zhanjiang Ctr Translat Med, Shanghai 201203, Peoples R China. RP Shi, LM (reprint author), Fudan Univ, Ctr Pharmacogen, State Key Lab Genet Engn, Shanghai 201203, Peoples R China. EM leming.shi@gmail.com FU China's Program of Global Experts; China's National Supercomputing Center of Tianjin; FDA Office of Women's Health FX The authors gratefully acknowledge experimental support of many collaborators who were listed as coauthors of the paper8 on the initial analysis of the data set described in this manuscript. This work was supported in part by China's Program of Global Experts, China's National Supercomputing Center of Tianjin, and the FDA Office of Women's Health. The views presented in this article do not necessarily reflect current or future opinion or policy of the US Food and Drug Administration. Any mention of commercial products is for clarification and not intended as an endorsement. NR 20 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2052-4463 J9 SCI DATA JI Sci. Data PY 2014 VL 1 AR 140013 DI 10.1038/sdata.2014.13 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V45VG UT WOS:000209843500005 ER PT B AU Abraham, A Plakas, SM Dickey, RW AF Abraham, Ann Plakas, Steven M. Dickey, Robert W. BE Rossini, GP TI Chemistry of Brevetoxins SO TOXINS AND BIOLOGICALLY ACTIVE COMPOUNDS FROM MICROALGAE, VOL 1: ORIGIN, CHEMISTRY AND DETECTION LA English DT Article; Book Chapter ID OYSTER CRASSOSTREA-VIRGINICA; MUSSELS PERNA-CANALICULUS; TANDEM MASS-SPECTROMETRY; KARENIA-BREVIS CULTURES; NEW-ZEALAND; RED TIDE; AUSTROVENUS-STUTCHBURYI; PTYCHODISCUS-BREVIS; GREENSHELL MUSSELS; GYMNODINIUM-BREVE C1 [Abraham, Ann; Plakas, Steven M.; Dickey, Robert W.] US FDA, Div Seafood Sci & Technol, 1 Iberville Dr, Dauphin Isl, AL 36528 USA. RP Abraham, A (reprint author), US FDA, Div Seafood Sci & Technol, 1 Iberville Dr, Dauphin Isl, AL 36528 USA. EM ann.abraham@fda.hhs.gov; steven.plakas@fda.hhs.gov; robert.dickey@fda.hhs.gov NR 49 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 978-1-4822-1069-9; 978-1-4822-1068-2 PY 2014 BP 153 EP 175 PG 23 WC Plant Sciences; Toxicology SC Plant Sciences; Toxicology GA BF7MJ UT WOS:000384234600007 ER PT B AU Hungerford, JM AF Hungerford, James M. BE Rossini, GP TI Marine Toxin Detection Methods in Regulation-From Validation to Implementation SO TOXINS AND BIOLOGICALLY ACTIVE COMPOUNDS FROM MICROALGAE, VOL 1: ORIGIN, CHEMISTRY AND DETECTION LA English DT Article; Book Chapter ID PARALYTIC SHELLFISH TOXINS; SINGLE-LABORATORY VALIDATION; LIQUID-CHROMATOGRAPHY; POISONING TOXINS; PRECHROMATOGRAPHIC OXIDATION; QUANTITATIVE-DETERMINATION; FLUORESCENCE DETECTION; MOUSE BIOASSAY; PSP TOXINS; OYSTERS C1 [Hungerford, James M.] US FDA, ATC, PRL NW, AOAC Marine & Freshwater Toxins Task Force, 22201 23rd Dr SE, Bothell, WA 98021 USA. RP Hungerford, JM (reprint author), US FDA, ATC, PRL NW, AOAC Marine & Freshwater Toxins Task Force, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM James.Hungerford@fda.gov NR 47 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 978-1-4822-1069-9; 978-1-4822-1068-2 PY 2014 BP 487 EP 502 PG 16 WC Plant Sciences; Toxicology SC Plant Sciences; Toxicology GA BF7MJ UT WOS:000384234600016 ER PT B AU Deeds, JR AF Deeds, Jonathan R. BE Rossini, GP TI Toxicity of Palytoxins: From Cellular to Organism Level Responses SO TOXINS AND BIOLOGICALLY ACTIVE COMPOUNDS FROM MICROALGAE VOL 2: BIOLOGICAL EFFECTS AND RISK MANAGEMENT LA English DT Article; Book Chapter ID DINOFLAGELLATE OSTREOPSIS-SIAMENSIS; FRENCH MEDITERRANEAN COAST; OF-THE-ART; HAFF-DISEASE; PUTATIVE PALYTOXIN; MARINE TOXIN; OVATOXIN-A; STRUCTURE ELUCIDATION; RIBOTOXIC STRESS; 1ST EVIDENCE C1 [Deeds, Jonathan R.] US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. RP Deeds, JR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM jonathan.deeds@fda.hhs.gov NR 96 TC 0 Z9 0 U1 1 U2 1 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4822-3147-2; 978-1-4822-3146-5 PY 2014 BP 351 EP 378 PG 28 WC Plant Sciences; Toxicology SC Plant Sciences; Toxicology GA BF7MH UT WOS:000384234100014 ER PT B AU Byrnes, AP Huang, Y Shannon, K AF Byrnes, Andrew P. Huang, Ying Shannon, Kevin BE Lattime, EC Gerson, SL TI The FDA Review Process for Cancer Gene Therapy SO GENE THERAPY OF CANCER: TRANSLATIONAL APPROACHES FROM PRECLINICAL STUDIES TO CLINICAL IMPLEMENTATION, 3RD EDITION LA English DT Article; Book Chapter DE FDA; CBER; cancer gene therapy; regulatory review; CMC; pharmacology/toxicology; clinical; drug development ID EXPRESSION; MODELS; CELLS; ANGIOGENESIS; MELANOMA; VECTOR AB This chapter provides an overview of the U. S. Food and Drug Administration (FDA) review process for cancer gene therapy products. Cancer gene therapy products are reviewed within FDA's Center for Biologics Evaluation and Research (CBER). Although there are currently no FDA-approved gene therapies, CBER works with academic and industry sponsors during all stages of product development. CBER's roles range from giving scientific advice to providing regulatory oversight to ensure the appropriate and safe treatment of human subjects. CBER teams composed of experts in various disciplines (chemistry/manufacturing/controls, pharmacology/toxicology, clinical, biostatistics, and regulatory project managers) review product and manufacturing issues, preclinical assessment, and clinical trial design at all stages of product development. This chapter summarizes CBER's functions and highlights some issues that are of particular importance for sponsors of cancer gene therapy trials. References with further regulatory guidance and information are provided. C1 [Byrnes, Andrew P.; Huang, Ying; Shannon, Kevin] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Byrnes, AP (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 45 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-394632-4; 978-0-12-394295-1 PY 2014 BP 503 EP 515 DI 10.1016/B978-0-12-394295-1.00035-4 PG 13 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA BIE16 UT WOS:000327801200041 ER PT J AU Srivaths, PR Goldstein, SL Krishnamurthy, R Silverstein, DM AF Srivaths, Poyyapakkam R. Goldstein, Stuart L. Krishnamurthy, Rajesh Silverstein, Douglas M. TI High serum phosphorus and FGF 23 levels are associated with progression of coronary calcifications SO PEDIATRIC NEPHROLOGY LA English DT Article DE Hemodialysis; Pediatric; Children ID CHRONIC-KIDNEY-DISEASE; STAGE RENAL-DISEASE; LEFT-VENTRICULAR HYPERTROPHY; HEMODIALYSIS-PATIENTS; VASCULAR CALCIFICATION; ARTERY CALCIFICATION; CARDIOVASCULAR-DISEASE; YOUNG-ADULTS; DIALYSIS; CHILDREN AB Coronary calcifications (CC) portend increased mortality in adults receiving hemodialysis (HD), however the risk factors associated with CC progression are not well known in pediatric patients. Our previous cross-sectional studies demonstrated high CC prevalence (31 %) in pediatric patients, which were significantly associated with high serum phosphorus (P), fibroblast growth factor 23 (FGF) levels, dialysis vintage, and low cholesterol. The current study was undertaken to determine and elucidate CC progression in pediatric HD patients. A 1-year prospective longitudinal study of 16 pediatric patients (ten male; mean age, 16.9 +/- 3 years; range, 10.1-20.4 years) receiving chronic HD was conducted. CC were observed in five of 16 (31.3 %) patients on baseline computed tomogram (CT) scan; 14/16 patients underwent 1-year CT. All patients with initial CC who completed CT at 1 year (3/5) progressed; one patient had new CC and none of the patients had resolved CC. Mean Agatston score increased from 23.4 +/- 18.06 HU (baseline) to 169 +/- 298.9 HU. Patients with CC progression had higher mean serum P (8.6 +/- 1.8 mg/dl vs. 6.3 +/- 1.1 mg/dl, p = 0.015) and FGF 23 levels (3,994 +/- 860.5 pg/ml vs. 2,327 +/- 1,206.4 pg/ml, p = 0.028). Serum P and FGF 23 levels were positively correlated with final Agatston scores (R = 0.65, p = 0.01 for serum P and R = 0.54, p = 0.045 for FGF 23) and change in Agatston scores (R = 0.65, p = 0.01 for serum P and R = 0.52, p = 0.048 for FGF 23). Our study shows that CC is progressive in pediatric patients receiving HD and that increased serum P and FGF 23 levels are associated with this progression. C1 [Srivaths, Poyyapakkam R.] Baylor Coll Med, Texas Childrens Hosp Pediat Nephrol, Houston, TX 77030 USA. [Goldstein, Stuart L.] Cincinnati Childrens Hosp, Sect Pediat Nephrol, Cincinnati, OH USA. [Krishnamurthy, Rajesh] Baylor Coll Med, Texas Childrens Hosp Radiol, Houston, TX 77030 USA. [Silverstein, Douglas M.] US FDA, Renal Devices Branch, Silver Spring, MD USA. RP Srivaths, PR (reprint author), Baylor Coll Med, Texas Childrens Hosp Pediat Nephrol, 6621 Fannin St,MC 3-2482, Houston, TX 77030 USA. EM srivaths@bcm.edu NR 37 TC 3 Z9 4 U1 0 U2 5 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 JAN PY 2014 VL 29 IS 1 BP 103 EP 109 DI 10.1007/s00467-013-2575-8 PG 7 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 264LB UT WOS:000327877600012 PM 23921492 ER PT B AU Kahook, MY AF Kahook, Malik Y. BE Kahook, MY TI MIGS Advances in Glaucoma Surgery INTRODUCTION SO MIGS: ADVANCES IN GLAUCOMA SURGERY LA English DT Editorial Material; Book Chapter C1 [Kahook, Malik Y.] Univ Colorado, Sch Med, Denver, CO 80202 USA. [Kahook, Malik Y.] Univ Colorado, Ctr Eye, Denver, CO 80202 USA. [Kahook, Malik Y.] Univ Colorado, Ctr Eye, Glaucoma Serv, Denver, CO 80202 USA. [Kahook, Malik Y.] US FDA, Ophthalm Device Div, Rockville, MD 20857 USA. [Kahook, Malik Y.] Univ Colorado, Rocky Mt Lions Eye Inst, Denver, CO 80202 USA. RP Kahook, MY (reprint author), Univ Colorado, Sch Med, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-600-1 PY 2014 BP XV EP XV PG 1 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BHN74 UT WOS:000326000800001 ER PT B AU SooHoo, JR Kahook, MY Seibold, LK AF SooHoo, Jeffrey R. Kahook, Malik Y. Seibold, Leonard K. BE Kahook, MY TI Basic Anatomy and Wound-Healing Considerations for MIGS SO MIGS: ADVANCES IN GLAUCOMA SURGERY LA English DT Article; Book Chapter ID AQUEOUS OUTFLOW; GLAUCOMA; CYCLOPHOTOCOAGULATION; NEODYMIUM; EYE C1 [SooHoo, Jeffrey R.] Univ Colorado, Sch Med, Dept Ophthalmol, Aurora, CO 80045 USA. [Kahook, Malik Y.] Univ Colorado, Sch Med, Denver, CO USA. [Kahook, Malik Y.] Univ Colorado, Ctr Eye, Denver, CO 80202 USA. [Kahook, Malik Y.] Univ Colorado, Ctr Eye, Glaucoma Serv, Denver, CO 80202 USA. [Kahook, Malik Y.] US FDA, Ophthalm Device Div, Rockville, MD 20857 USA. [Kahook, Malik Y.] Univ Colorado, Rocky Mt Lions Eye Inst, Denver, CO 80202 USA. [Seibold, Leonard K.] Univ Colorado, Sch Med, Dept Ophthalmol, Boulder, CO 80309 USA. RP SooHoo, JR (reprint author), Univ Colorado, Sch Med, Dept Ophthalmol, Aurora, CO 80045 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-600-1 PY 2014 BP 17 EP 25 PG 9 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BHN74 UT WOS:000326000800004 ER PT B AU Ittoop, SM Kahook, MY Seibold, LK AF Ittoop, Sabita M. Kahook, Malik Y. Seibold, Leonard K. BE Kahook, MY TI Trabecular Meshwork Bypass Devices SO MIGS: ADVANCES IN GLAUCOMA SURGERY LA English DT Article; Book Chapter ID OPEN-ANGLE GLAUCOMA; STENT IMPLANTATION; CATARACT-SURGERY; PHACOEMULSIFICATION C1 [Ittoop, Sabita M.] Univ Colorado Denver, Dept Ophthalmol, Aurora, CO 80045 USA. [Kahook, Malik Y.] Univ Colorado, Sch Med, Denver, CO USA. [Kahook, Malik Y.] Univ Colorado, Ctr Eye, Denver, CO 80202 USA. [Kahook, Malik Y.] Univ Colorado, Ctr Eye, Glaucoma Serv, Denver, CO 80202 USA. [Kahook, Malik Y.] US FDA, Ophthalm Device Div, Rockville, MD 20857 USA. [Kahook, Malik Y.] Univ Colorado, Rocky Mt Lions Eye Inst, Denver, CO 80202 USA. [Seibold, Leonard K.] Univ Colorado, Sch Med, Dept Ophthalmol, Denver, CO USA. RP Ittoop, SM (reprint author), Univ Colorado Denver, Dept Ophthalmol, Aurora, CO 80045 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-600-1 PY 2014 BP 27 EP 35 PG 9 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BHN74 UT WOS:000326000800005 ER PT J AU Baker, MA Nguyen, M Cole, DV Lee, GM Lieu, TA AF Baker, Meghan A. Michael Nguyen Cole, David V. Lee, Grace M. Lieu, Tracy A. TI Post-licensure rapid immunization safety monitoring program (PRISM) data characterization SO VACCINE LA English DT Article DE Mini-Sentinel; PRISM; Vaccine; Health outcome; Data characterization; Surveillance ID GUILLAIN-BARRE-SYNDROME; EVENT REPORTING SYSTEM; ACUTE DISSEMINATED ENCEPHALOMYELITIS; INTRANASAL INFLUENZA VACCINE; HENOCH-SCHONLEIN PURPURA; REAL-TIME SURVEILLANCE; RHEUMATOID-ARTHRITIS; FEBRILE SEIZURES; ADVERSE EVENTS; UNITED-STATES AB Background: The Post-Licensure Rapid Immunization Safety Monitoring (PRISM) program is the immunization safety monitoring component of FDA's Mini-Sentinel project, a program to actively monitor the safety of medical products using electronic health information. FDA sought to assess the surveillance capabilities of this large claims-based distributed database for vaccine safety surveillance by characterizing the underlying data. Methods: We characterized data available on vaccine exposures in PRISM, estimated how much additional data was gained by matching with select state and local immunization registries, and compared vaccination coverage estimates based on PRISM data with other available data sources. We generated rates of computerized codes representing potential health outcomes relevant to vaccine safety monitoring. Standardized algorithms including ICD-9 codes, number of codes required, exclusion criteria and location of the encounter were used to obtain the background rates. Results: The majority of the vaccines routinely administered to infants, children, adolescents and adults were well captured by claims data Immunization registry data in up to seven states comprised between 5% and 9% of data for all vaccine categories with the exception of 10% for hepatitis B and 3% and 4% for rotavirus and zoster respectively. Vaccination coverage estimates based on PRISM's computerized data were similar to but lower than coverage estimates from the National Immunization Survey and Healthcare Effectiveness Data and Information Set. For the 25 health outcomes of interest studied, the rates of potential outcomes based on ICD-9 codes were generally higher than rates described in the literature, which are typically clinically confirmed cases. Conclusion: PRISM program's data on vaccine exposures and health outcomes appear complete enough to support robust safety monitoring. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Baker, Meghan A.; Cole, David V.; Lee, Grace M.; Lieu, Tracy A.] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. [Baker, Meghan A.; Cole, David V.; Lee, Grace M.; Lieu, Tracy A.] Harvard Univ, Sch Med, Boston, MA USA. [Baker, Meghan A.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. [Michael Nguyen] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Lee, Grace M.] Boston Childrens Hosp, Dept Med, Div Infect Dis, Boston, MA USA. RP Baker, MA (reprint author), Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. EM meghan_baker@harvardpilgrim.org; Michael.Nguyen@fda.hhs.gov; david_cole@harvardpilgrim.org; Grace.Lee@childrens.harvard.edu; tracy.lieu@kp.org FU Food and Drug Administration (FDA) through Department of Health and Human Services (HHS) [HHSF223200910006I]; Mini-Sentinel program FX Mini-Sentinel is funded by the Food and Drug Administration (FDA) through Department of Health and Human Services (HHS) Contract Number HHSF223200910006I. The views expressed in this document do not necessarily reflect the official policies of the Department of Health and Human Services, nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. government.; We thank Richard Platt, M.D., M.Sc., Jeffrey Brown, Ph.D., and Nicolas Beaulieu, M.A., for their support via the leadership of the Mini-Sentinel program and its distributed database and Robert Rosofsky, M.A. for his work on the de-duplication of vaccine and immunization registry data. We also thank Sunali Goonesekera, M.Sc. for her help with references. Finally, we greatly appreciate the input of the PRISM team on vaccine and health outcome codes and algorithms. NR 80 TC 4 Z9 4 U1 0 U2 7 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 30 PY 2013 VL 31 SU 10 BP K98 EP K112 DI 10.1016/j.vaccine.2013.04.088 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 289LS UT WOS:000329684600012 PM 24331080 ER PT J AU Chung, CP Rohan, P Krishnaswami, S McPheeters, ML AF Chung, Cecilia P. Rohan, Patricia Krishnaswami, Shanthi McPheeters, Melissa L. TI A systematic review of validated methods for identifying patients with rheumatoid arthritis using administrative or claims data SO VACCINE LA English DT Review DE Rheumatoid arthritis; Validation; Administrative database; ICD-9; Positive predictive value; Algorithm ID MODIFYING ANTIRHEUMATIC DRUGS; POPULATION-BASED COHORT; FACTOR-ALPHA ANTAGONISTS; HEALTH-CARE UTILIZATION; ACUTE MYOCARDIAL-INFARCTION; INFLAMMATORY-BOWEL-DISEASE; SAFETY MONITORING PROGRAM; CONGESTIVE-HEART-FAILURE; UNITED-STATES; AUTOIMMUNE-DISEASES AB Purpose: To review the evidence supporting the validity of billing, procedural, or diagnosis code, or pharmacy claim-based algorithms used to identify patients with rheumatoid arthritis (RA) in administrative and claim databases. Methods: We searched the MEDLINE database from 1991 to September 2012 using controlled vocabulary and key terms related to RA and reference lists of included studies were searched. Two investigators independently assessed the full text of studies against pre-determined inclusion criteria and extracted the data. Data collected included participant and algorithm characteristics. Results: Nine studies reported validation of computer algorithms based on International Classification of Diseases (ICD) codes with or without free-text, medication use, laboratory data and the need for a diagnosis by a rheumatologist. These studies yielded positive predictive values (PPV) ranging from 34 to 97% to identify patients with RA. Higher PPVs were obtained with the use of at least two ICD and/or procedure codes (ICD-9 code 714 and others), the requirement of a prescription of a medication used to treat RA, or requirement of participation of a rheumatologist in patient care. For example, the PPV increased from 66 to 97% when the use of disease-modifying antirheumatic drugs and the presence of a positive rheumatoid factor were required. Conclusions: There have been substantial efforts to propose and validate algorithms to identify patients with RA in automated databases. Algorithms that include more than one code and incorporate medications or laboratory data and/or required a diagnosis by a rheumatologist may increase the PPV. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Chung, Cecilia P.] Vanderbilt Univ, Sch Med, Med Ctr N, Div Rheumatol, Nashville, TN 37232 USA. [Rohan, Patricia] US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Rockville, MD 20852 USA. [Krishnaswami, Shanthi; McPheeters, Melissa L.] Vanderbilt Univ, Med Ctr, Vanderbilt Evidence Based Practice Ctr, Nashville, TN 37203 USA. [McPheeters, Melissa L.] Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol, Nashville, TN 37203 USA. RP Chung, CP (reprint author), Vanderbilt Univ, Sch Med, Med Ctr N, Div Rheumatol, 1161 21st Ave South,D-3100, Nashville, TN 37232 USA. EM c.chung@vanderbilt.edu; shanthi.krishnaswami@vanderbilt.edu; melissa.mcpheeters@vanderbilt.edu FU Food and Drug Administration (FDA) through Department of Health and Human Services (HHS) [HHSF223200910006I]; Vanderbilt Physician Scientist Development Award FX Mini-Sentinel is funded by the Food and Drug Administration (FDA) through Department of Health and Human Services (HHS) Contract Number HHSF223200910006I. The views expressed in this document do not necessarily reflect the official policies of the Department of Health and Human Services, nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. government. CPC was funded by the Vanderbilt Physician Scientist Development Award. NR 117 TC 18 Z9 18 U1 0 U2 4 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 30 PY 2013 VL 31 SU 10 BP K41 EP K61 DI 10.1016/j.vaccine.2013.03.075 PG 21 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 289LS UT WOS:000329684600007 PM 24331074 ER PT J AU Lu, TP Chuang, EY Chen, JJ AF Lu, Tzu-Pin Chuang, Eric Y. Chen, James J. TI Identification of reproducible gene expression signatures in lung adenocarcinoma SO BMC BIOINFORMATICS LA English DT Article DE Lung adenocarcinoma; Microarray; Pathway analysis; Prognostic biomarker; Predictive biomarker ID THERAPEUTIC TARGET; PREDICT SURVIVAL; CANCER; CELL; PATHWAYS; CHEMOTHERAPY; METAANALYSIS; ASSOCIATION; SENSITIVITY; VANDETANIB AB Background: Lung cancer is the leading cause of cancer-related death worldwide. Tremendous research efforts have been devoted to improving treatment procedures, but the average five-year overall survival rates are still less than 20%. Many biomarkers have been identified for predicting survival; challenges arise, however, in translating the findings into clinical practice due to their inconsistency and irreproducibility. In this study, we proposed an approach by identifying predictive genes through pathways. Results: The microarrays from Shedden et al. were used as the training set, and the log-rank test was performed to select potential signature genes. We focused on 24 cancer-related pathways from 4 biological databases. A scoring scheme was developed by the Cox hazard regression model, and patients were divided into two groups based on the medians. Subsequently, their predictability and generalizability were evaluated by the 2-fold cross-validation and a resampling test in 4 independent datasets, respectively. A set of 16 genes related to apoptosis execution was demonstrated to have good predictability as well as generalizability in more than 700 lung adenocarcinoma patients and was reproducible in 4 independent datasets. This signature set was shown to have superior performances compared to 6 other published signatures. Furthermore, the corresponding risk scores derived from the set were found to associate with the efficacy of the anti-cancer drug ZD-6474 targeting EGFR. Conclusions: In summary, we presented a new approach to identify reproducible survival predictors for lung adenocarcinoma, and the identified genes may serve as both prognostic and predictive biomarkers in the future. C1 [Lu, Tzu-Pin; Chen, James J.] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Little Rock, AR USA. [Lu, Tzu-Pin; Chuang, Eric Y.] Natl Taiwan Univ, YongLin Biomed Engn Ctr, Taipei 10764, Taiwan. [Chuang, Eric Y.] Natl Taiwan Univ, Grad Inst Biomed Engn & Bioinformat, Taipei 10764, Taiwan. [Chen, James J.] China Med Univ, Grad Inst Biostat, Taichung, Taiwan. [Chen, James J.] China Med Univ, Ctr Biostat, Taichung, Taiwan. RP Chen, JJ (reprint author), US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Little Rock, AR USA. EM jamesj.chen@fda.hhs.gov OI LU, TZU-PIN/0000-0003-3697-0386 NR 48 TC 4 Z9 4 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD DEC 26 PY 2013 VL 14 AR UNSP 371 DI 10.1186/1471-2105-14-371 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 292MU UT WOS:000329906800001 PM 24369726 ER PT J AU Gomberg-Maitland, M Bull, TM Saggar, R Barst, RJ Elgazayerly, A Fleming, TR Grimminger, F Rainisio, M Stewart, DJ Stockbridge, N Ventura, C Ghofrani, AH Rubin, LJ AF Gomberg-Maitland, Mardi Bull, Todd M. Saggar, Rajeev Barst, Robyn J. Elgazayerly, Amany Fleming, Thomas R. Grimminger, Friedrich Rainisio, Maurizio Stewart, Duncan J. Stockbridge, Norman Ventura, Carlo Ghofrani, Ardeschir H. Rubin, Lewis J. TI New Trial Designs and Potential Therapies for Pulmonary Artery Hypertension SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review DE ethics; pulmonary arterial hypertension; therapeutics; trial designs ID EXTRACORPOREAL MEMBRANE-OXYGENATION; VASOACTIVE-INTESTINAL-PEPTIDE; SMOOTH-MUSCLE-CELLS; RIGHT-VENTRICULAR HYPERTROPHY; TYROSINE KINASE INHIBITOR; OUTCOMES PRO INSTRUMENTS; SURROGATE END-POINTS; INHALED NITRIC-OXIDE; IMATINIB MESYLATE; HEART-FAILURE AB A greater understanding of the epidemiology, pathogenesis, and pathophysiology of pulmonary artery hypertension (PAH) has led to significant advances, but the disease remains fatal. Treatment options are neither universally available nor always effective, underscoring the need for development of novel therapies and therapeutic strategies. Clinical trials to date have provided evidence of efficacy, but were limited in evaluating the scope and duration of treatment effects. Numerous potential targets in varied stages of drug development exist, in addition to novel uses of familiar therapies. The pursuit of gene and cell-based therapy continues, and device use to help acute deterioration and chronic management is emerging. This rapid surge of drug development has led to multicenter pivotal clinical trials and has resulted in novel ethical and global clinical trial concerns. This paper will provide an overview of the opportunities and challenges that await the development of novel treatments for PAH. (C) 2013 by the American College of Cardiology Foundation C1 [Gomberg-Maitland, Mardi] Univ Chicago, Dept Med, Cardiol Sect, Chicago, IL 60637 USA. [Bull, Todd M.] Univ Colorado, Dept Med, Sect Pulm & Crit Care, Aurora, CO USA. [Saggar, Rajeev] Heart & Lung Inst, Phoenix, AZ USA. [Barst, Robyn J.] Columbia Univ, New York, NY USA. [Elgazayerly, Amany] European Med Agcy, London, England. [Fleming, Thomas R.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Grimminger, Friedrich; Ghofrani, Ardeschir H.] Univ Hosp Giessen, Dept Med Oncol, Dept Med, Sect Pulm, Giessen, Germany. [Rainisio, Maurizio] AbaNovus, San Remo, Italy. [Stewart, Duncan J.] Ottawa Hosp Res Inst, Dept Med, Sect Cardiol, Ottawa, ON, Canada. [Stockbridge, Norman] US FDA, White Oak, MD USA. [Ventura, Carlo] Univ Bologna, Dept Med, Sect Cardiol, Bologna, Italy. [Rubin, Lewis J.] Univ Calif San Diego, Dept Med, Sect Pulm & Crit Care, San Diego, CA 92103 USA. RP Gomberg-Maitland, M (reprint author), Univ Chicago, Pulm Hypertens Program, Dept Med, Cardiol Sect, 5841 South Maryland Ave,MC5403, Chicago, IL 60611 USA. EM mgomberg@bsd.uchicago.edu FU Actelion; Gilead; Medtronic; Novartis; United Therapeutics; Bayer Schering; Pfizer; Ergonex; Encysive; GlaxoSmithKline FX Dr. Saggar contributed to the manuscript until September 1, 2013, when he became an employee of United Therapeutics. Dr. Barst is deceased. The opinions expressed herein might not reflect the official opinions of the Food and Drug Administration or the European Medical Agencies. Dr. Gomberg-Maitland has received institutional grant support from Actelion, Gilead, Medtronic and Novartis as principal investigator through the University of Chicago; and has served as a consultant to and/or on steering committees, scientific advisory boards, or data safety monitoring for Actelion, Gilead, Medtronic, Merck, and Ikaria. Dr. Bull has received an investigator initiated grant from United Therapeutics; and has served on the advisory board of Actelion. Dr. Saggar has a relationship with EvoLung LLC; has served on the advisory board of Gilead; and is a United Therapeutics employee as of September 1, 2013. Dr. Fleming has served as a consultant to Actelion and Pfizer. Dr. Grimminger has received research grants from Bayer Schering, Pfizer, Ergonex, and Encysive; has received honoraria payments from Bayer Schering, Pfizer, Actelion, Encysive, and Novartis Pharmaceuticals; and has a consultancy and/or advisory board relationship with Nycomed (Altana Pharma). Dr. Stewart has had relationships with Northern Therapeutics and United Therapeutics. Dr. Ghofrani has relationships with Actelion, Bayer, GlaxoSmithKline, Merck, Novartis, and Pfizer. Dr. Rubin has relationships with United Therapeutics, Bayer, GeNO, the National Heart, and Blood Institute, the U. S. Food and Drug Administration, Actelion, Lung LLC, Gilead, Reata Pharmaceuticals, Arena Pharmaceuticals, and Aires Pharmaceuticals; and has served as a consultant for Aires Pharmaceuticals and GeNO. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 103 TC 49 Z9 49 U1 1 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 24 PY 2013 VL 62 IS 25 SU S BP D82 EP D91 DI 10.1016/j.jacc.2013.10.026 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 286HW UT WOS:000329459400010 PM 24355645 ER PT J AU Lamart, S Imran, R Simon, SL Doi, K Morton, LM Curtis, RE Lee, C Drozdovitch, V Maass-Moreno, R Chen, CC Whatley, M Miller, DL Pacak, K Lee, C AF Lamart, Stephanie Imran, Rebecca Simon, Steven L. Doi, Kazutaka Morton, Lindsay M. Curtis, Rochelle E. Lee, Choonik Drozdovitch, Vladimir Maass-Moreno, Roberto Chen, Clara C. Whatley, Millie Miller, Donald L. Pacak, Karel Lee, Choonsik TI Prediction of the location and size of the stomach using patient characteristics for retrospective radiation dose estimation following radiotherapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID POSITION; THERAPY; CANCER AB Following cancer radiotherapy, reconstruction of doses to organs, other than the target organ, is of interest for retrospective health risk studies. Reliable estimation of doses to organs that may be partially within or fully outside the treatment field requires reliable knowledge of the location and size of the organs, e.g., the stomach, which is at risk from abdominal irradiation. The stomach location and size are known to be highly variable between individuals, but have been little studied. Moreover, for treatments conducted years ago, medical images of patients are usually not available in medical records to locate the stomach. In light of the poor information available to locate the stomach in historical dose reconstructions, the purpose of this work was to investigate the variability of stomach location and size among adult male patients and to develop prediction models for the stomach location and size using predictor variables generally available in medical records of radiotherapy patients treated in the past. To collect data on stomach size and position, we segmented the contours of the stomach and of the skeleton on contemporary computed tomography (CT) images for 30 male patients in supine position. The location and size of the stomach was found to depend on body mass index (BMI), ponderal index (PI), and age. For example, the anteroposterior dimension of the stomach was found to increase with increasing BMI (approximate to 0.25 cm kg(-1) m(2)) whereas its craniocaudal dimension decreased with increasing PI (approximate to-3.3 cm kg(-1) m(3)) and its transverse dimension increased with increasing PI (approximate to 2.5 cm kg(-1) m(3)). Using the prediction models, we generated three-dimensional computational stomach models from a deformable hybrid phantom for three patients of different BMI. Based on a typical radiotherapy treatment, we simulated radiotherapy treatments on the predicted stomach models and on the CT images of the corresponding patients. Those dose calculations demonstrated good agreement between predicted and actual stomachs compared with doses derived from a reference model of the body that might be used in the absence of individual CT scan data. C1 [Lamart, Stephanie; Imran, Rebecca; Simon, Steven L.; Doi, Kazutaka; Morton, Lindsay M.; Curtis, Rochelle E.; Drozdovitch, Vladimir; Lee, Choonsik] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Lee, Choonik] Univ Michigan Hosp, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. [Maass-Moreno, Roberto; Chen, Clara C.; Miller, Donald L.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Whatley, Millie] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, NIH, Bethesda, MD USA. RP Lamart, S (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM leechoonsik@mail.nih.gov RI Morton, Lindsay/B-5234-2015; Lee, Choonsik/C-9023-2015 OI Morton, Lindsay/0000-0001-9767-2310; Lee, Choonsik/0000-0003-4289-9870 FU National Cancer Institute FX 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). This work was supported by the National Cancer Institute's intramural research program. NR 16 TC 4 Z9 4 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD DEC 21 PY 2013 VL 58 IS 24 BP 8739 EP 8753 DI 10.1088/0031-9155/58/24/8739 PG 15 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 266SG UT WOS:000328043400011 PM 24301086 ER PT J AU Foley, C Harvey, E Bidol, SA Henderson, T Njord, R DeSalvo, T Haupt, T Mba-Jonas, A Bailey, C Bopp, C Bosch, SA Gerner-Smidt, P Mody, RK Nguyen, TA Strockbine, N Tauxe, RV AF Foley, Catherine Harvey, Emily Bidol, Sally A. Henderson, Tiffany Njord, Rebecca DeSalvo, Traci Haupt, Thomas Mba-Jonas, Adamma Bailey, Chris Bopp, Cheryl Bosch, Stacey A. Gerner-Smidt, Peter Mody, Rajal K. Thai-An Nguyen Strockbine, Nancy Tauxe, Robert V. TI Outbreak of Escherichia coli O104:H4 Infections Associated with Sprout Consumption - Europe and North America, May-July 2011 SO MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT LA English DT Article C1 [Harvey, Emily] Massachusetts Dept Publ Hlth, Boston, MA 02111 USA. [Mba-Jonas, Adamma] US FDA, Dept Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Bailey, Chris; Bopp, Cheryl; Bosch, Stacey A.; Gerner-Smidt, Peter; Mody, Rajal K.; Thai-An Nguyen; Strockbine, Nancy; Tauxe, Robert V.] CDC, Div Foodborne Waterborne & Environm Dis, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA. RP Mba-Jonas, A (reprint author), US FDA, Dept Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM adamma.mba-jonas@fda.hhs.gov NR 10 TC 11 Z9 11 U1 0 U2 5 PU CENTER DISEASE CONTROL & PREVENTION PI ATLANTA PA MAILSTOP E-90, ATLANTA, GA 30333 USA SN 0149-2195 EI 1545-861X J9 MMWR-MORBID MORTAL W JI MMWR-Morb. Mortal. Wkly. Rep. PD DEC 20 PY 2013 VL 62 IS 50 BP 1029 EP 1031 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 278AX UT WOS:000328861500003 ER PT J AU Collins, FS Hamburg, MA AF Collins, Francis S. Hamburg, Margaret A. TI First FDA Authorization for Next-Generation Sequencer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material AB The FDA has granted marketing authorization for a high-throughput genomic sequencer, Illumina's MiSeqDx, which will allow the development of innumerable new genome-based tests. Access to genomic data may transform research, clinical care, and patient engagement. This year marks 60 years since James Watson and Francis Crick described the structure of DNA and 10 years since the complete sequencing of the human genome. Fittingly, today the Food and Drug Administration (FDA) has granted marketing authorization for the first high-throughput (next-generation) genomic sequencer, Illumina's MiSeqDx, which will allow the development and use of innumerable new genome-based tests. When a global team of researchers sequenced that first human genome, it took more than a decade and cost hundreds of millions of dollars. Today, because of federal and private investment, sequencing technologies have advanced dramatically, and a human genome ... C1 [Collins, Francis S.] NIH, Off Director, Bethesda, MD 20892 USA. [Hamburg, Margaret A.] US Dept HHS, US FDA, Off Commissioner, Silver Spring, MD USA. RP Collins, FS (reprint author), NIH, Off Director, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 86 Z9 91 U1 2 U2 6 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 19 PY 2013 VL 369 IS 25 BP 2369 EP 2371 DI 10.1056/NEJMp1314561 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 274DQ UT WOS:000328586000003 PM 24251383 ER PT J AU Lo, SC Li, BJ Hung, GC Lei, HY Li, TW Zhang, J Nagamine, K Tsai, SE Zucker, MJ Olesnicky, L AF Lo, Shyh-Ching Li, Bingjie Hung, Guo-Chiuan Lei, Haiyan Li, Tianwei Zhang, Jing Nagamine, Kenjiro Tsai, Shien Zucker, Mark J. Olesnicky, Ludmilla TI Isolation and Characterization of Two Novel Bacteria Afipia cberi and Mesorhizobium hominis from Blood of a Patient Afflicted with Fatal Pulmonary Illness SO PLOS ONE LA English DT Article ID SP-NOV; ALPHA-PROTEOBACTERIA; SEQUENCE; INFECTIONS; STRAIN; STABILITY; CULTURE; FELIS AB We recently isolated and discovered new Bradyrhizobiaceae microbes from the cryopreserved culture broth of blood samples from 3 patients with poorly defined illnesses using modified SP4 media and culture conditions coupled with genomic sequencing. Using a similar protocol, we studied a previously cryopreserved culture broth of blood sample from a patient who had succumbed to an acute onset of fulminant pulmonary illness. We report that two phases of microbial growth were observed in the re-initiated culture. Biochemical and genomic characterization revealed microbes isolated from the first phase of growth were new Afipia species of Bradyrhizobiaceae, tentatively named A. cberi with a similar to 5 MB chromosome that was different from those of all previously known Afipia microbes including the newly discovered A. septicemium. The microbes isolated from the second phase of growth were prominent sugar assimilators, novel Phyllobacteriaceae, phylogenetically most closely related to Mesorhizobium and tentatively named M. hominis with a similar to 5.5 MB chromosome. All A. cberi isolates carry a circular similar to 140 KB plasmid. Some M. hominis isolates possess a circular similar to 412 KB plasmid that can be lost in prolonged culture or passage. No antibiotics resistant genes could be identified in both of the A. cberi and M. hominis plasmids. Antibiotic susceptibility studies using broth culture systems revealed isolates of A. cberi could be sensitive to some antibiotics, but all isolates of M. hominis were resistant to essentially all tested antibiotics. However, the cell-free antibiotics susceptibility test results may not be applicable to clinical treatment against the microbes that are known to be capable of intracellular growth. It remains to be determined if the 2 previously unknown Rhizobiales were indeed pathogenic and played a role in the pulmonary disease process in this patient. Specific probes and methods will be developed to re-examine the diseased lungs from patient's autopsy. C1 [Lo, Shyh-Ching; Li, Bingjie; Hung, Guo-Chiuan; Lei, Haiyan; Li, Tianwei; Zhang, Jing; Nagamine, Kenjiro; Tsai, Shien] US FDA, Tissue Microbiol Lab, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies,Ctr Biol Eva, Bethesda, MD 20014 USA. [Zucker, Mark J.] Newark Beth Israel Med Ctr, Dept Med, Newark, NJ USA. [Olesnicky, Ludmilla] Newark Beth Israel Med Ctr, Dept Pathol, Newark, NJ USA. RP Lo, SC (reprint author), US FDA, Tissue Microbiol Lab, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies,Ctr Biol Eva, Bethesda, MD 20014 USA. EM shyhching.lo@fda.hhs.gov FU FDA Modernizing Science Intramural Grant FX The study was supported in part by FDA Modernizing Science Intramural Grant entitled "A new approach of detection and/or discovery of previously unknown pathogens". The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study. NR 30 TC 5 Z9 5 U1 0 U2 13 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 18 PY 2013 VL 8 IS 12 AR e82673 DI 10.1371/journal.pone.0082673 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 276HL UT WOS:000328740300054 PM 24367538 ER PT J AU Krause, PR Bialek, SR Boppana, SB Griffiths, PD Laughlin, CA Ljungman, P Mocarski, ES Pass, RF Read, JS Schleiss, MR Plotkin, SA AF Krause, Philip R. Bialek, Stephanie R. Boppana, Suresh B. Griffiths, Paul D. Laughlin, Catherine A. Ljungman, Per Mocarski, Edward S. Pass, Robert F. Read, Jennifer S. Schleiss, Mark R. Plotkin, Stanley A. TI Priorities for CMV vaccine development SO VACCINE LA English DT Review DE Cytomegalovirus; Congenital CMV; Viruses; Clinical trial endpoints; Meeting report ID CONGENITAL CYTOMEGALOVIRUS-INFECTION; ORGAN TRANSPLANT RECIPIENTS; BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; GLYCOPROTEIN-B VACCINE; DOUBLE-BLIND; ADVISORY-COMMITTEE; HEARING-LOSS; DISEASE; IMMUNIZATION AB A multidisciplinary meeting addressed priorities related to development of vaccines against cytomegalovirus (CMV), the cause of congenital CMV (cCMV) disease and of serious disease in the immunocompromised. Participants discussed optimal uses of a CMV vaccine, aspects of clinical study design, and the value of additional research. A universal childhood CMV vaccine could potentially rapidly reduce cCMV disease, as infected children are sources of viral transmission to seronegative and seropositive mothers. A vaccine administered to adolescents or adult women could also reduce cCMV disease by making them immune prior to pregnancy. Clinical trials of CMV vaccines in women should evaluate protection against cCMV infection, an essential precursor of cCMV disease, which is a more practical and acceptable endpoint for assessing vaccine effects on maternal-fetal transmission. Clinical trials of vaccines to evaluate prevention of CMV disease in stem cell transplant recipients could use CMV viremia at a level triggering pre-emptive antiviral therapy as an endpoint, because widespread use of pre-emptive and prophylactic antivirals has rendered CMV-induced disease too rare to be a practical endpoint for clinical trials. In solid organ transplant patients, CMV-associated disease is sufficiently common for use as a primary endpoint. Additional research to advance CMV vaccine development should include identifying factors that predict fetal loss due to CMV, determining age-specific incidence and transmission rates, defining the mechanism and relative contributions of maternal reactivation and reinfection to cCMV disease, developing assays that can distinguish between reactivation and re-infection in seropositive vaccinees, further defining predictors of sequelae from cCMV infection, and identifying clinically relevant immune response parameters to CMV (including developing validated assays that could assess CMV antibody avidity) that could lead to the establishment of immune correlates of protection. Published by Elsevier Ltd. C1 [Krause, Philip R.] US FDA, Off Vaccines Res & Review, CBER, Bethesda, MD 20014 USA. [Bialek, Stephanie R.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Boppana, Suresh B.; Pass, Robert F.] Univ Alabama Birmingham, Birmingham, AL USA. [Griffiths, Paul D.] UCL, London WC1E 6BT, England. [Laughlin, Catherine A.] NIAID, NIH, Bethesda, MD USA. [Ljungman, Per] Karolinska Inst, Stockholm, Sweden. [Mocarski, Edward S.] Emory Univ, Atlanta, GA 30322 USA. [Read, Jennifer S.] Natl Vaccine Program Off, Washington, DC USA. [Schleiss, Mark R.] Univ Minnesota, Minneapolis, MN USA. [Plotkin, Stanley A.] Univ Penn, Philadelphia, PA 19104 USA. RP Krause, PR (reprint author), US FDA, Off Vaccines Res & Review, CBER, 29 Lincoln Dr, Bethesda, MD 20014 USA. EM philip.krause@fda.hhs.gov; zqg7@cdc.gov; sboppana@peds.uab.edu; p.griffiths@ucl.ac.uk; CLaughlin@niaid.nih.gov; Per.Ljungman@ki.se; mocarski@emory.edu; RPass@peds.uab.edu; Jennifer.Read@fda.hhs.gov; schleiss@umn.edu; stanley.plotkin@vaxconsult.com OI Krause, Philip/0000-0002-1045-7536 FU Food and Drug Administration; National Institutes of Health; Centers for Disease Control and Prevention; National Vaccine Program Office FX We acknowledge the Food and Drug Administration, the National Institutes of Health, the Centers for Disease Control and Prevention, and the National Vaccine Program Office for sponsorship of the CMV Vaccine Workshop, held in Bethesda, MD on the NIH Campus on January 11-12, 2012. We also thank the presenters and participants at the meeting for excellent discussions that enabled a highly productive meeting. NR 55 TC 36 Z9 37 U1 0 U2 7 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 17 PY 2013 VL 32 IS 1 BP 4 EP 10 DI 10.1016/j.vaccine.2013.09.042 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 289LT UT WOS:000329684700003 PM 24129123 ER PT J AU Pope, CR De Feo, CJ Unger, VM AF Pope, Christopher R. De Feo, Christopher J. Unger, Vinzenz M. TI Cellular distribution of copper to superoxide dismutase involves scaffolding by membranes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE membrane scaffold; copper homeostasis; copper transfer; copper uptake ID AMYOTROPHIC-LATERAL-SCLEROSIS; SACCHAROMYCES-CEREVISIAE; 2-DIMENSIONAL CRYSTALLIZATION; NEURODEGENERATIVE DISEASES; CHAPERONE CCS; YEAST; GLUTATHIONE; OXYGEN; SOD1; DIMERIZATION AB Efficient delivery of copper ions to specific intracellular targets requires copper chaperones that acquire metal cargo through unknown mechanisms. Here we demonstrate that the human and yeast copper chaperones (CCS) for superoxide dismutase 1 (SOD1), long thought to exclusively reside in the cytosol and mitochondrial intermembrane space, can engage negatively charged bilayers through a positively charged lipid-binding interface. The significance of this membrane-binding interface is established through SOD1 activity and genetic complementation studies in Saccharomyces cerevisiae, showing that recruitment of CCS to the membrane is required for activation of SOD1. Moreover, we show that a CCS: SOD1 complex binds to bilayers in vitro and that CCS can interact with human high affinity copper transporter 1. Shifting current paradigms, we propose that CCS-dependent copper acquisition and distribution largely occur at membrane interfaces and that this emerging role of the bilayer may reflect a general mechanistic aspect of cellular transition metal ion acquisition. C1 [Pope, Christopher R.; Unger, Vinzenz M.] Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA. [Pope, Christopher R.; Unger, Vinzenz M.] Northwestern Univ, Chem Life Proc Inst, Evanston, IL 60208 USA. [De Feo, Christopher J.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Unger, VM (reprint author), Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA. EM v-unger@northwestern.edu FU [F31 NS076213]; [F31 NS56825]; [GM094479] FX We thank Valeria Culotta and coworkers for the S. cerevisiae reagents and guidance with the in vivo complementation studies. We thank Dennis Winge for many helpful discussions and critical suggestions. We also thank Krasimir Spasov and Jose Olvera for construct preparation and experimental advice throughout the course of this project. This work was supported by predoctoral fellowships F31 NS076213 (to C. R. P.), F31 NS56825 (to C.J.D.F.), and GM094479 (to V.M.U.). NR 41 TC 18 Z9 18 U1 1 U2 9 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 DEC 17 PY 2013 VL 110 IS 51 BP 20491 EP 20496 DI 10.1073/pnas.1309820110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 273PR UT WOS:000328548600042 PM 24297923 ER PT J AU Kluetz, PG Ning, YM Maher, VE Zhang, LJ Tang, SH Ghosh, D Aziz, R Palmby, T Pfuma, E Zirkelbach, JF Mehrotra, N Tilley, A Sridhara, R Ibrahim, A Justice, R Pazdur, R AF Kluetz, Paul G. Ning, Yang-Min Maher, V. Ellen Zhang, Lijun Tang, Shenghui Ghosh, Debasis Aziz, Robeena Palmby, Todd Pfuma, Elimika Zirkelbach, Jeanne Fourie Mehrotra, Nitin Tilley, Amy Sridhara, Rajeshwari Ibrahim, Amna Justice, Robert Pazdur, Richard TI Abiraterone Acetate in Combination with Prednisone for the Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer: US Food and Drug Administration Drug Approval Summary SO CLINICAL CANCER RESEARCH LA English DT Article ID CLINICAL-TRIALS; WORKING GROUP; END-POINTS; PHASE-II; DOCETAXEL; MITOXANTRONE; RECOMMENDATIONS; SURVIVAL AB On December 10, 2012, the U. S. Food and Drug Administration granted full approval for a modified indication for abiraterone acetate (Zytiga tablets; Janssen Biotech, Inc.) in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). The approval was based on clinical trial COU-AA-302, which randomly allocated asymptomatic or mildly symptomatic patients with chemotherapy-naive mCRPC and no visceral metastases to either abiraterone acetate plus prednisone (N = 546) or placebo plus prednisone (N 542). The coprimary endpoints were radiographic progression-free survival (rPFS) and overall survival (OS). The median rPFS was 8.3 months in the placebo arm and had not yet been reached in the abiraterone acetate arm {HR, 0.43 [95% confidence interval (CI) 0.35-0.52]; P < 0.0001}. A prespecified interim analysis demonstrated an improvement in OS favoring the abiraterone acetate arm [HR, 0.79 (95% CI, 0.66-0.96)] but did not cross the O'Brien-Fleming boundary for statistical significance. Safety data confirmed the known adverse reaction profile of abiraterone acetate. Full approval was granted on the basis of a large magnitude of effect on rPFS, a favorable trend in OS, and internal consistency across multiple secondary endpoints and exploratory patient-reported pain data. This is the first drug approval for mCRPC to use rPFS as the primary endpoint. Importantly, this approval was granted in the context of a prior statistically significant OS benefit that formed the basis of the original April 28, 2011, approval of abiraterone acetate for patients with mCRPC who had received prior chemotherapy containing docetaxel. (C) 2013 AACR. C1 [Kluetz, Paul G.; Ning, Yang-Min; Maher, V. Ellen; Aziz, Robeena; Palmby, Todd; Tilley, Amy; Ibrahim, Amna; Justice, Robert; Pazdur, Richard] US FDA, Ctr Drug Evaluat & Res, Off Hematol & Oncol Prod, Off NewDrugs, Silver Spring, MD 20993 USA. [Zhang, Lijun; Tang, Shenghui; Sridhara, Rajeshwari] US FDA, Ctr Drug Evaluat & Res, Off Biostat, Silver Spring, MD 20993 USA. [Pfuma, Elimika; Zirkelbach, Jeanne Fourie; Mehrotra, Nitin] US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD 20993 USA. [Ghosh, Debasis] US FDA, Ctr Drug Evaluat & Res, Off New Drug Qual Assessment, Silver Spring, MD 20993 USA. RP Kluetz, PG (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Hematol & Oncol Prod, 10903 New Hampshire Ave,Bldg 22,2223, Silver Spring, MD 20993 USA. EM kluetzpa@cder.fda.gov; ningy@cder.fda.gov NR 18 TC 22 Z9 23 U1 1 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 15 PY 2013 VL 19 IS 24 BP 6650 EP 6656 DI 10.1158/1078-0432.CCR-13-2134 PG 7 WC Oncology SC Oncology GA 279CY UT WOS:000328938700002 PM 24150234 ER PT J AU Vaclavikova, M MacMahon, S Zhang, K Begley, TH AF Vaclavikova, Marta MacMahon, Shaun Zhang, Kai Begley, Timothy H. TI Application of single immunoaffinity clean-up for simultaneous determination of regulated mycotoxins in cereals and nuts SO TALANTA LA English DT Article DE Mycotoxins; Multi-target analysis; Immunoaffinity clean-up; Nuts; Cereals; UHPLC-MS/MS ID MASS-SPECTROMETRY; FOOD AB A rapid and sensitive analytical strategy for the simultaneous determination of twelve mycotoxins (aflatoxins, fumonisins, zearalenon, deoxynivalenol, ochratoxin A, T-2 and HT-2 toxins) using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) was developed and validated. The method was validated for peanuts, barley and maize-breakfast cereals; selected as they represent the matrices most often contaminated by mycotoxins. The method is designed for fast and reliable analyses of mycotoxins in regulatory, industrial and private laboratories. Multi-target immunoaffinity columns containing antibodies for all mycotoxins studied herein were used for sample clean-up. Method optimization was predominantly focused on the simplification of extraction and cleanup procedure recommended by column producers. This newly developed and simplified procedure decreased both the sample preparation time and the solvent volumes used for their processing. The analysis of all regulated mycotoxins was conducted by a newly developed UHPLC-MS/MS method with a sample run time of only ten minutes. The method trueness was tested with analytical spikes and certified reference materials, with recoveries ranging from 71% to 112% for all of the examined mycotoxins. Published by Elsevier B.V. C1 [Vaclavikova, Marta; MacMahon, Shaun; Zhang, Kai; Begley, Timothy H.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. RP Vaclavikova, M (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, 5100 Paint Branch Pkwy,HFS-706, College Pk, MD 20740 USA. EM Marta.Vaclavikova@fda.hhs.gov FU appointment to the Research Participation Program at the Center for Food Safety and the Applied Nutrition FX MV acknowledges the support 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 U.S. Department of Energy and the U.S. Food and Drug Administration. NR 14 TC 13 Z9 15 U1 4 U2 64 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0039-9140 EI 1873-3573 J9 TALANTA JI Talanta PD DEC 15 PY 2013 VL 117 BP 345 EP 351 DI 10.1016/j.talanta.2013.09.007 PG 7 WC Chemistry, Analytical SC Chemistry GA 277EI UT WOS:000328801400051 PM 24209351 ER PT J AU Valencia, A Prous, J Mora, O Sadrieh, N Valerio, LG AF Valencia, Antoni Prous, Josep Mora, Oscar Sadrieh, Nakissa Valerio, Luis G., Jr. TI A novel QSAR model of Salmonella mutagenicity and its application in the safety assessment of drug impurities SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Safety; Mutagenicity; QSAR; Modeling; Binned algorithms; Computational toxicology ID CARCINOGENICITY; PREDICTION; VALIDATION; GENOTOXICITY; AGREEMENT; SUPPORT AB As indicated in ICH M7 draft guidance, in silico predictive tools including statistically-based QSARs and expert analysis may be used as a computational assessment for bacterial mutagenicity for the qualification of impurities in pharmaceuticals. To address this need, we developed and validated a QSAR model to predict Salmonella t. mutagenicity (Ames assay outcome) of pharmaceutical impurities using Prous Institute's Symmetry(SM), a new in silico solution for drug discovery and toxicity screening, and the Mold2 molecular descriptor package (FDA/NCTR). Data was sourced from public benchmark databases with known Ames assay mutagenicity outcomes for 7300 chemicals (57% mutagens). Of these data, 90% was used to train the model and the remaining 10% was set aside as a holdout set for validation. The model's applicability to drug impurities was tested using a FDA/CDER database of 951 structures, of which 94% were found within the model's applicability domain. The predictive performance of the model is acceptable for supporting regulatory decision-making with 84 +/- 1% sensitivity, 81 +/- 1% specificity, 83 +/- 1% concordance and 79 +/- 1% negative predictivity based on internal cross-validation, while the holdout dataset yielded 83% sensitivity, 77% specificity, 80% concordance and 78% negative predictivity. Given the importance of having confidence in negative predictions, an additional external validation of the model was also carried out, using marketed drugs known to be Ames-negative, and obtained 98% coverage and 81% specificity. Additionally, Ames mutagenicity data from FDA/CFSAN was used to create another data set of 1535 chemicals for external validation of the model, yielding 98% coverage, 73% sensitivity, 86% specificity, 81% concordance and 84% negative predictivity. Published by Elsevier Inc. C1 [Valencia, Antoni; Prous, Josep; Mora, Oscar] Prous Inst Biomed Res, Barcelona 08008, Spain. [Sadrieh, Nakissa; Valerio, Luis G., Jr.] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Valerio, LG (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, White Oak 51 Room 4150,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM luis.valerio@fda.hhs.gov NR 30 TC 6 Z9 6 U1 2 U2 25 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 2013 VL 273 IS 3 BP 427 EP 434 DI 10.1016/j.taap.2013.09.015 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 275XC UT WOS:000328711700001 PM 24090816 ER PT J AU Grundy, HH Read, WA Macarthur, R Dickinson, M Charlton, AJ Dusek, M Breidbach, A Scholl, PF Newsome, GA Bell, D Alewijn, M AF Grundy, H. H. Read, W. A. Macarthur, R. Dickinson, M. Charlton, A. J. Dusek, M. Breidbach, A. Scholl, P. F. Newsome, G. A. Bell, D. Alewijn, M. TI Selected reaction monitoring method to determine the species origin of blood-based binding agents in meats: A collaborative study SO FOOD CHEMISTRY LA English DT Article DE Thrombin; Binding agent; Bovine and porcine blood; Food authenticity; Selected reaction monitoring; Collaborative trial; LC-MS/MS ID QUADRUPOLE MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; PRODUCTS; VALIDATION AB Binding products or food 'glues' are used throughout the food industry to increase the meat use rate or to augment economic efficiency. Some of these binders contain thrombin from bovine and porcine blood. The European parliament has recently banned thrombin-based additives and labelling legislation governs their use in the US. A mass spectrometry screening method is available to detect the addition of thrombin agents to foods as there is a need to protect consumers and to avoid misleading trade practices. We report the details of an inter-laboratory trial to determine the transferability of this method to operators in various food testing laboratories, each using a different triple quadrupole mass spectrometer design. The trial was successful with the species origin of the binding agent contained in each of the 43 test materials being correctly reported by the participants. This is consistent with a false positive and false negative rate of 0%. This is the first collaborative study, as far as we are aware, which involves a liquid chromatography mass spectrometry (LC-MS/MS) application to approach a food authenticity issue. Crown Copyright (c) 2013 Published by Elsevier Ltd. All rights reserved. C1 [Grundy, H. H.; Read, W. A.; Macarthur, R.; Dickinson, M.; Charlton, A. J.] Food & Environm Res Agcy, York YO41 1LZ, N Yorkshire, England. [Dusek, M.] Czech Agr & Food Inspect Author, Prague 150005, Czech Republic. [Breidbach, A.] European Commiss, Joint Res Ctr, Inst Reference Mat & Measurements, B-2440 Geel, Belgium. [Newsome, G. A.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Bell, D.] Lab Govt Chemist, Teddington TW11 0LY, Middx, England. [Alewijn, M.] Rikilt Inst Food Safety, NL-6708 WB Wageningen, Netherlands. RP Grundy, HH (reprint author), Food & Environm Res Agcy, York YO41 1LZ, N Yorkshire, England. EM helen.grundy@fera.gsi.gov.uk RI Newsome, G. Asher/J-8970-2012; OI Newsome, G. Asher/0000-0003-1683-2197; Scholl, Peter/0000-0002-8870-3266 FU Evidence and Knowledge Base Science Team at the Department for Environment, Food and Rural Affairs (Defra) [FA0107]; Authenticity Programme at the Food Standards Agency [Q01093] FX We gratefully acknowledge funding from the Evidence and Knowledge Base Science Team at the Department for Environment, Food and Rural Affairs (Defra, Project FA0107) for funding this collaborative study. We also thank the Authenticity Programme at the Food Standards Agency for funding earlier work to develop the method used during this trial (Grant number Q01093). We would also like to thank Mark Sykes of FAPAS (R) for proof reading this manuscript. NR 12 TC 1 Z9 1 U1 2 U2 40 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 DEC 15 PY 2013 VL 141 IS 4 BP 3531 EP 3536 DI 10.1016/j.foodchem.2013.06.063 PG 6 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 223YI UT WOS:000324848000034 PM 23993517 ER PT J AU Zineh, I Pacanowski, M Woodcock, J AF Zineh, Issam Pacanowski, Michael Woodcock, Janet TI Pharmacogenetics and Coumarin Dosing - Recalibrating Expectations SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID EFFICACY C1 [Zineh, Issam; Pacanowski, Michael; Woodcock, Janet] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Zineh, I (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 4 TC 30 Z9 31 U1 0 U2 4 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 12 PY 2013 VL 369 IS 24 BP 2273 EP 2275 DI 10.1056/NEJMp1314529 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 268FV UT WOS:000328156300002 PM 24328463 ER PT J AU Chen, XR Zhang, YB Yan, J Sadiq, R Chen, T AF Chen, Xinrong Zhang, Yongbin Yan, Jian Sadiq, Rakhshinda Chen, Tao TI miR-34a suppresses mutagenesis by inducing apoptosis in human lymphoblastoid TK6 cells SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE miR-34a; Mutagenesis; Apoptosis ID IN-VITRO MICRONUCLEUS; DIPLOID HUMAN-LYMPHOBLASTS; TARGET MESSENGER-RNAS; SMALL INTERFERING RNA; TUMOR-SUPPRESSOR; DNA-DAMAGE; MUTATION ASSAY; NBS1 KNOCKDOWN; WORKING GROUP; RAT-LIVER AB miR-34a, a tumor suppressor miRNA, has been identified as a direct transcriptional target of P53. miRNA precursors and inhibitors have been used to modulate the expression of their targeted mRNA and thereby study miRNA functions. We indicated in our previous work that X-ray induces miR-34a expression in a time and dose dependent manner. The objective of this study was to elucidate the role of miR-34a in X-ray-induced mutations in human lymphoblast TK6 cells. Neither over-expression of miR-34a by lipid transfection of miR-34a precursor nor down regulation of endogenous miR-34a by miR-34a inhibitor had any effect on X-ray-induced micronucleus frequency in TK6 cells. Over-expression of miR-34a in TK6 cells significantly reduced X-ray induced mutant frequency (MF) in the Thymidine Kinase (TK) locus while suppression of endogenous miR-34a can increase the background level MF in TK6 cells. Furthermore, over-expression of miR-34a promoted and down-regulation of miR-34a inhibited background and Xray-induced apoptosis in TK6 cells. Our study suggests miR-34a is an important negative regulator of mutagenesis and the mechanism is possibly mediated through apoptosis. Published by Elsevier B.V. C1 [Chen, Xinrong; Yan, Jian; Sadiq, Rakhshinda; Chen, Tao] Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Food & Drug Adm, Jefferson, AR 72079 USA. [Zhang, Yongbin] Natl Ctr Toxicol Res, Off Sci Coordinat, Food & Drug Adm, Jefferson, AR 72079 USA. RP Chen, T (reprint author), NCTR, HFT 130,3900 NCTR Rd, Jefferson, AR 72079 USA. EM xinrong.Chen@fda.hhs.gov; yongbin.Zhang@fda.hhs.gov; Jian.yan@fda.hhs.gov; rakhshinda.Sadiq@fda.hhs.gov; tao.chen@fda.hhs.gov FU U.S. Food and Drug Administration FX This work was supported by the commissioner's fellowship program in U.S. Food and Drug Administration. NR 45 TC 0 Z9 0 U1 1 U2 5 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 DEC 12 PY 2013 VL 758 IS 1-2 BP 35 EP 40 DI 10.1016/j.mrgentox.2013.08.010 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 276CB UT WOS:000328724600007 PM 24025418 ER PT J AU Kashoki, M Lee, C Jenkins, J AF Kashoki, Mwango Lee, Cathryn Jenkins, John TI Drug Postmarketing Studies SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Kashoki, Mwango; Lee, Cathryn; Jenkins, John] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Kashoki, M (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,WO 22,Room 6464, Silver Spring, MD 20993 USA. EM mwango.kashoki@fda.hhs.gov NR 3 TC 0 Z9 0 U1 0 U2 0 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 11 PY 2013 VL 310 IS 22 BP 2459 EP 2459 DI 10.1001/jama.2013.278901 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 266NN UT WOS:000328030900032 PM 24327044 ER PT J AU Sharma, GM Khuda, SE Pereira, M Slate, A Jackson, LS Pardo, C Williams, KM Whitaker, TB AF Sharma, Girdhari M. Khuda, Sefat E. Pereira, Marion Slate, Andrew Jackson, Lauren S. Pardo, Christopher Williams, Kristina M. Whitaker, Thomas B. TI Development of an Incurred Cornbread Model for Gluten Detection by Immunoassays SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Gluten; ELISA; immunoassay; incurred food; thermal processing ID IMMUNOCHEMICAL ANALYTICAL METHODS; MULTIPLE ALLERGENS; PEANUT PROTEINS; ELISA DETECTION; CELIAC-DISEASE; WHEAT; FOODS; MATRIX; PREVALENCE; RECOVERY AB Gluten that is present in food as a result of cross-contact or misbranding can cause severe health concerns to wheat-allergic and celiac patients. Immunoassays, such as enzyme-linked immunosorbent assay (ELISA) and lateral flow device (LFD), are commonly used to detect gluten traces in foods. However, the performance of immunoassays can be affected by non-assay-related factors, such as food matrix and processing conditions. Gluten (0-500 ppm) and wheat flour (20-1000 ppm) incurred cornbread was prepared at different incurred levels and baking conditions (204.4 degrees C for 20, 27, and 34 min) to study the accuracy and precision of gluten measurement by seven immunoassay kits (three LFD and four ELISA kits). The stability and immunoreactivity of gluten proteins, as measured by western blot using three different antibodies, were not adversely affected by the baking conditions. However, the gluten recovery varied depending upon the ELISA kit and the gluten source used to make the incurred cornbread, affecting the accuracy of gluten quantification (BioKits, 9-77%; Morinaga, 91-137%; R-Biopharm, 61 -108%; and Romer Labs, 113-190%). Gluten recovery was reduced with increased baking time for most ELISA kits analyzed. Both the sampling and analytical variance increased with an increase in the gluten incurred level. The predicted analytical coefficient of variation associated with all ELISA kits was below 12% for all incurred levels, indicative of good analytical precision. C1 [Sharma, Girdhari M.; Khuda, Sefat E.; Pereira, Marion; Williams, Kristina M.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Slate, Andrew; Whitaker, Thomas B.] N Carolina State Univ, Dept Biol & Agr Engn, Raleigh, NC 27695 USA. [Jackson, Lauren S.; Pardo, Christopher] US FDA, Ctr Food Safety & Appl Nutr, Bedford Pk, IL 60501 USA. RP Sharma, GM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM girdhari.sharma@fda.hhs.gov NR 26 TC 8 Z9 8 U1 2 U2 18 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 11 PY 2013 VL 61 IS 49 BP 12146 EP 12154 DI 10.1021/jf404072x PG 9 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 272DE UT WOS:000328439700034 PM 24245605 ER PT J AU Chen, ZC Fischer, ER Kouiavskaia, D Hansen, BT Ludtke, SJ Bidzhieva, B Makiya, M Agulto, L Purcell, RH Chumakov, K AF Chen, Zhaochun Fischer, Elizabeth R. Kouiavskaia, Diana Hansen, Bryan T. Ludtke, Steven J. Bidzhieva, Bella Makiya, Michelle Agulto, Liane Purcell, Robert H. Chumakov, Konstantin TI Cross-neutralizing human anti-poliovirus antibodies bind the recognition site for cellular receptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE phage display; passive immunization; antiviral therapy; broadly reactive antibodies ID ELECTRON-MICROSCOPY; ANTIGENIC STRUCTURE; MONOCLONAL-ANTIBODIES; COMPLEXES; ERADICATION; MUTANTS; VIRUS; CD155; RNA AB Most structural information about poliovirus interaction with neutralizing antibodies was obtained in the 1980s in studies of mouse monoclonal antibodies. Recently we have isolated a number of human/chimpanzee anti-poliovirus antibodies and demonstrated that one of them, MAb A12, could neutralize polioviruses of both serotypes 1 and 2. This communication presents data on isolation of an additional cross-neutralizing antibody (F12) and identification of a previously unknown epitope on the surface of poliovirus virions. Epitope mapping was performed by sequencing of antibody-resistant mutants and by cryo-EM of complexes of virions with Fab fragments. The results have demonstrated that both cross-neutralizing antibodies bind the site located at the bottom of the canyon surrounding the fivefold axis of symmetry that was previously shown to interact with cellular poliovirus receptor CD155. However, the same antibody binds to serotypes 1 and 2 through different specific interactions. It was also shown to interact with type 3 poliovirus, albeit with about 10-fold lower affinity, insufficient for effective neutralization. Antibody interaction with the binding site of the cellular receptor may explain its broad reactivity and suggest that further screening or antibody engineering could lead to a universal antibody capable of neutralizing all three serotypes of poliovirus. C1 [Chen, Zhaochun; Makiya, Michelle; Agulto, Liane; Purcell, Robert H.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Fischer, Elizabeth R.; Hansen, Bryan T.] NIAID, Electron Microscopy Unit, Res Technol Branch, Rocky Mt Labs, Hamilton, MT 59840 USA. [Kouiavskaia, Diana; Bidzhieva, Bella; Chumakov, Konstantin] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Ludtke, Steven J.] Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Natl Ctr Macromol Imaging, Houston, TX 77030 USA. RP Purcell, RH (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM robert.purcell@nih.gov; konstantin.chumakov@fda.hhs.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health; Food and Drug Administration Center for Biologics Evaluation and Research; NIH [R01-GM080139] FX This work was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, the Food and Drug Administration Center for Biologics Evaluation and Research, and NIH Grant R01-GM080139 (to S.L.). NR 31 TC 16 Z9 16 U1 1 U2 10 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 DEC 10 PY 2013 VL 110 IS 50 BP 20242 EP 20247 DI 10.1073/pnas.1320041110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 266YY UT WOS:000328061700066 PM 24277851 ER PT J AU Ali, MM Minor, T Amialchuk, A AF Ali, Mir M. Minor, Travis Amialchuk, Aliaksandr TI Estimating the Biases Associated with Self-Perceived, Self-Reported, and Measured BMI on Mental Health SO PLOS ONE LA English DT Article ID BODY-MASS INDEX; OBESITY; ADOLESCENTS; WEIGHT; DEPRESSION; RISK AB Purpose: The purpose of the study is to explore the relationship between individuals' perceptions of their weight-status, self-reported height and weight, and measured weight status. Methods: A national survey of 9,248 adolescents (47% male) between the ages of 11 and 27 is analyzed to determine whether inaccuracies in reporting are caused by misperception or conscious intent, and whether there tends to be a systematic bias in how individuals self-report. Self-esteem was used as an example of an important outcome variable in order to illustrate the magnitudes of the biases that may arise when using different measures of body size. Results: Our results indicate that measured obesity status is associated with the reduction in Rosenberg Self-Esteem (RSE) of 0.30 points (p-value 0.005) among adolescents and 0.20 points (p-value 0.002) among young adults; in addition, using self-reported height and weight as opposed to measured height and weight does not result in a statistically detectable difference in the estimates. Conclusions: Individuals' self-reports of height and weight are not as unreliable as we might have expected. Although estimates from measured height and weight are preferred, in the absence of such measures, self-reported measures would likely be a reliable alternative. The differences in self-perception of weight status, however, imply that it is not comparable to measured weight categories. C1 [Ali, Mir M.] Subst Abuse & Mental Hlth Serv Adm, Anal & Serv Res Branch, Rockville, MD USA. [Minor, Travis] US FDA, Off Regulat Policy & Social Sci, College Pk, MD USA. [Amialchuk, Aliaksandr] Univ Toledo, Dept Econ, Toledo, OH 43606 USA. RP Ali, MM (reprint author), Subst Abuse & Mental Hlth Serv Adm, Anal & Serv Res Branch, Rockville, MD USA. EM mir.ali@samhsa.hhs.gov OI Minor, Travis/0000-0002-5297-7695 FU National Institute of Child Health and Human Development [P01-HD31921] FX The views expressed here are those of the authors and do not necessarily reflect the views of the Substance Abuse & Mental Health Services Administration or the Food & Drug Administration. This research uses data from Add Health, a program project designed by J. Richard Udry Peter S. Bearman, and Kathleen Mullan Harris, and funded by a grant P01-HD31921 from the National Institute of Child Health and Human Development, with cooperative funding from 17 other agencies. Special acknowledgment is due Ronald R. Rindfuss and Barbara Entwisle for assistance in the original design. Persons interested in obtaining data files from Add Health should contact Add Health, Carolina Population Center, 123 W. Franklin Street, Chapel Hill, NC 27516-2524 (addhealth@unc.edu). NR 17 TC 3 Z9 3 U1 1 U2 19 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 4 PY 2013 VL 8 IS 12 AR e81021 DI 10.1371/journal.pone.0081021 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 265KD UT WOS:000327949300067 PM 24324658 ER PT J AU Revollo, JR Oakley, RH Lu, NZ Kadmiel, M Gandhavadi, M Cidlowski, JA AF Revollo, Javier R. Oakley, Robert H. Lu, Nick Z. Kadmiel, Mahita Gandhavadi, Maheer Cidlowski, John A. TI HES1 Is a Master Regulator of Glucocorticoid Receptor-Dependent Gene Expression SO SCIENCE SIGNALING LA English DT Article ID HELIX FACTOR HES-1; NEURONAL DIFFERENTIATION; FUNCTIONAL-ANALYSIS; TRANSGENIC MICE; LOOP; MECHANISMS; PROMOTER; INSULIN; NOTCH; RESISTANCE AB Hairy and enhancer of split-1 (HES1) is a basic helix-loop-helix transcription factor that is a key regulator of development and organogenesis. However, little is known about the role of HES1 after birth. Glucocorticoids, primary stress hormones that are essential for life, regulate numerous homeostatic processes that permit vertebrates to cope with physiological challenges. The molecular actions of glucocorticoids are mediated by glucocorticoid receptor-dependent regulation of nearly 25% of the genome. Here, we established a genome-wide molecular link between HES1 and glucocorticoid receptors that controls the ability of cells and animals to respond to stress. Glucocorticoid signaling rapidly and robustly silenced HES1 expression. This glucocorticoid-dependent repression of HES1 was necessary for the glucocorticoid receptor to regulate many of its target genes. Mice with conditional knockout of HES1 in the liver exhibited an expanded glucocorticoid receptor signaling profile and aberrant metabolic phenotype. Our results indicate that HES1 acts as a master repressor, the silencing of which is required for proper glucocorticoid signaling. C1 [Revollo, Javier R.; Oakley, Robert H.; Lu, Nick Z.; Kadmiel, Mahita; Gandhavadi, Maheer; Cidlowski, John A.] NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Revollo, Javier R.] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Lu, Nick Z.] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Allergy Immunol, Chicago, IL 60611 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. EM cidlows1@niehs.nih.gov FU Intramural Research Program of the NIH, NIEHS FX Funding: This research was supported by the Intramural Research Program of the NIH, NIEHS. Author contributions: J.R.R. designed and performed the experiments, analyzed the data, and wrote the manuscript. R.H.O. designed the experiments, analyzed the data, and wrote the manuscript. N.Z.L. designed and performed the experiments. M. K. designed and performed the experiments and analyzed the data. M. G. performed the experiments. J.A.C. designed the experiments, analyzed the data, and wrote the manuscript. NR 30 TC 10 Z9 10 U1 0 U2 8 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1945-0877 EI 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD DEC 3 PY 2013 VL 6 IS 304 AR ra103 DI 10.1126/scisignal.2004389 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 265HO UT WOS:000327941400001 PM 24300895 ER PT J AU Adedinsewo, DA Noory, L Bednarczyk, RA Steinhoff, MC Davis, R Ogbuanu, C Omer, SB AF Adedinsewo, Demilade A. Noory, Laila Bednarczyk, Robert A. Steinhoff, Mark C. Davis, Robert Ogbuanu, Chinelo Omer, Saad B. TI Impact of maternal characteristics on the effect of maternal influenza vaccination on fetal outcomes SO VACCINE LA English DT Article DE Influenza; Pregnancy; PRAMS; Preterm birth; Small for gestational age; Vaccine ID PROPENSITY SCORE; PREGNANCY; DIFFERENCE; WOMEN; MATCH; PROPORTIONS; COHORT; BIAS; US AB Background: Maternal infections during pregnancy have been associated with adverse fetal and infant health outcomes, and vaccination against influenza is the most effective tool to prevent morbidity and mortality due to seasonal and pandemic influenza. We evaluated the association between receipt of the inactivated seasonal influenza vaccine on preterm and small for gestational age (SGA) births, with the aim to assess racial and socioeconomic variations in vaccine effect. Methods: We conducted a retrospective analysis of state-wide surveillance data from Georgia for the most recent four years available at the beginning of the study, a total of 8393 live births in Georgia from January 1, 2005 through December 31, 2008. We constructed multivariable logistic regression models and calculated odds ratios (OR) estimates with corresponding 95% confidence intervals (CI) to evaluate the effect of maternal influenza vaccination on SGA (birth weight <10th percentile for gestational age) and preterm (gestational age at birth <37 weeks) births while controlling for potential confounders. Results: Among all women, we found significant strong associations between maternal influenza vaccination and reduced odds of a preterm birth during the widespread influenza activity period [OR=0.39, 95% CI: 0.18, 0.83]. In this period, vaccination was protective against SGA births among women at higher risk for influenza related morbidity - women enrolled in the Women, Infant and Child (WIC) program [OR=0.20, 95% CI: 0.04, 0.98] and Black women [OR=0.15 95% CI: 0.02, 0.94]; maternal influenza vaccination was associated with reduced odds of a preterm birth among white women [OR=0.34, 95% CI: 0.12, 0.91] and women of higher socio-economic status [OR=0.30, 95% CI: 0.12, 0.74]. Conclusion: Influenza vaccination during pregnancy was significantly associated with reduced odds of small for gestational age and preterm births during the widespread influenza activity period. Vaccination effects varied by socio-demographic characteristics. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Adedinsewo, Demilade A.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. [Noory, Laila] US FDA, Ctr Tobacco Prod, Off Sci, Washington, DC 20204 USA. [Bednarczyk, Robert A.; Omer, Saad B.] Emory Univ, Rollins Sch Publ Hlth, Hubert Dept Global Hlth, Atlanta, GA 30322 USA. [Steinhoff, Mark C.] Cincinnati Childrens Hosp Med Ctr, Childrens Global Hlth Ctr, Cincinnati, OH 45229 USA. [Bednarczyk, Robert A.; Davis, Robert; Omer, Saad B.] Kaiser Permanente Ctr Hlth Res, Atlanta, GA USA. [Omer, Saad B.] Emory Vaccine Ctr, Atlanta, GA USA. [Omer, Saad B.] Emory Univ, Sch Med & Childrens Healthcare Atlanta, Dept Pediat, Atlanta, GA 30322 USA. RP Omer, SB (reprint author), Emory Univ, Sch Publ Hlth, 1518 Clifton Rd, Atlanta, GA 30322 USA. EM demi.adedinsewo@gmail.com; lailasara@gmail.com; robert.a.bednarczyk@emory.edu; mark.steinhoff@cchmc.org; robert.l.davis@kp.org; chogbuanu@dhr.state.ga.us; somer@emory.edu OI Bednarczyk, Robert/0000-0002-6812-0928; Adedinsewo, Demilade/0000-0002-8629-2029 FU Kaiser Permanente Georgia community benefits grant FX Funding: The study was partially funded by a Kaiser Permanente Georgia community benefits grant. NR 38 TC 15 Z9 15 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 DEC 2 PY 2013 VL 31 IS 49 BP 5827 EP 5833 DI 10.1016/j.vaccine.2013.09.071 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 274GW UT WOS:000328595800007 PM 24120677 ER PT J AU Ruano-Rossil, JM AF Ruano-Rossil, Jorge M. TI The Unrecognized Role of the FDA Microanalytical Analyst SO MILITARY MEDICINE LA English DT Editorial Material C1 US FDA, Pacific Reg Lab South West, Irvine, CA 92612 USA. RP Ruano-Rossil, JM (reprint author), US FDA, Pacific Reg Lab South West, 19701 Fairchild, Irvine, CA 92612 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD DEC PY 2013 VL 178 IS 12 BP 1281 EP 1284 DI 10.7205/MILMED-D-13-00267 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AN7UF UT WOS:000340805800002 PM 24306008 ER PT J AU Ellingsen, AB Olsen, JS Granum, PE Rorvik, LM Gonzalez-Escalona, N AF Ellingsen, Anette B. Olsen, Jaran S. Granum, Per E. Rorvik, Liv M. Gonzalez-Escalona, Narjol TI Genetic characterization of trh positive Vibrio spp. isolated from Norway SO FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY LA English DT Article DE tdh; trh; V. parahaemolyticus; V. alginolyticus; MLST; urease; Vibrio; PCR ID THERMOSTABLE DIRECT HEMOLYSIN; PARAHAEMOLYTICUS PANDEMIC STRAINS; MULTIPLEX PCR; ALGINOLYTICUS STRAIN; PATHOGENIC VIBRIOS; ALASKAN OYSTERS; URE GENES; SEQUENCE; O3-K6; CHOLERAE AB The thermostable direct hemolysin (TDH) and/or TDH-related hemolysin (TRH) genes are carried by most virulent Vibrio parahaemolyticus serovars. In Norway, trh+ V parahaemolyncus constitute 4.4 and 4.5% of the total number of V. parahaemolyncus isolated from blue mussel (Mytilus edulis) and water, respectively. The trh gene is located in a region close to the gene cluster for urease production (ure). This region was characterized in V. parahaemolyticus strain TH3996 and it was found that a nickel transport operon (nik) was located between the first gene (ureR) and the rest of the ure cluster genes. The organization of the trh-ureR-nik-ure gene cluster in the Norwegian trh+ isolates was unknown. In this study, we explore the gene organization within the trh-ureR-nik-ure cluster for these isolates. PCR analyses revealed that the genes within the trh-ureR-nik-ure gene cluster of Norwegian trh+ isolates were organized in a similar fashion as reported previously for TH33996. Additionally, the phylogenetic relationship among these trh+ isolates was investigated using Multilocus Sequence Typing (MLST). Analysis by MLST or ureR-trh sequences generated two different phylogenetic trees for the same strains analyzed, suggesting that ureR-trh genes have been acquired at different times in Norwegian V. parahaemolyticus isolates. MLST results revealed that some pathogenic and non-pathogenic V. parahaemolyticus isolates in Norway appear to be highly genetically related. C1 [Ellingsen, Anette B.; Granum, Per E.; Rorvik, Liv M.] Norwegian Sch Vet Sci, Dept Food Safety & Infect Biol, Oslo, Norway. [Olsen, Jaran S.] Norwegian Def Res Estab, N-2007 Kjeller, Norway. [Gonzalez-Escalona, Narjol] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Gonzalez-Escalona, N (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy HFS 712, College Pk, MD 20740 USA. EM narjol.gonzalez-escalona@fda.hhs.gov OI Gonzalez-Escalona, Narjol/0000-0003-4568-0022 NR 55 TC 8 Z9 8 U1 2 U2 6 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 2235-2988 J9 FRONT CELL INFECT MI JI Front. Cell. Infect. Microbiol. PD DEC PY 2013 VL 3 AR 107 DI 10.3389/fcimb.2013.00107 PG 10 WC Immunology; Microbiology SC Immunology; Microbiology GA AC0SS UT WOS:000332205700020 PM 24400227 ER PT J AU Rice, SB Chan, C Brown, SC Eschbach, P Han, L Ensor, DS Stefaniak, AB Bonevich, J Vladar, AE Walker, ARH Zheng, JW Starnes, C Stromberg, A Ye, J Grulke, EA AF Rice, Stephen B. Chan, Christopher Brown, Scott C. Eschbach, Peter Han, Li Ensor, David S. Stefaniak, Aleksandr B. Bonevich, John Vladar, Andras E. Walker, Angela R. Hight Zheng, Jiwen Starnes, Catherine Stromberg, Arnold Ye, Jia Grulke, Eric A. TI Particle size distributions by transmission electron microscopy: an interlaboratory comparison case study SO METROLOGIA LA English DT Article AB This paper reports an interlaboratory comparison that evaluated a protocol for measuring and analysing the particle size distribution of discrete, metallic, spheroidal nanoparticles using transmission electron microscopy (TEM). The study was focused on automated image capture and automated particle analysis. NIST RM8012 gold nanoparticles (30 nm nominal diameter) were measured for area-equivalent diameter distributions by eight laboratories. Statistical analysis was used to (1) assess the data quality without using size distribution reference models, (2) determine reference model parameters for different size distribution reference models and non-linear regression fitting methods and (3) assess the measurement uncertainty of a size distribution parameter by using its coefficient of variation. The interlaboratory area-equivalent diameter mean, 27.6 nm +/- 2.4 nm (computed based on a normal distribution), was quite similar to the area-equivalent diameter, 27.6 nm, assigned to NIST RM8012. The lognormal reference model was the preferred choice for these particle size distributions as, for all laboratories, its parameters had lower relative standard errors (RSEs) than the other size distribution reference models tested (normal, Weibull and Rosin-Rammler-Bennett). The RSEs for the fitted standard deviations were two orders of magnitude higher than those for the fitted means, suggesting that most of the parameter estimate errors were associated with estimating the breadth of the distributions. The coefficients of variation for the interlaboratory statistics also confirmed the lognormal reference model as the preferred choice. From quasi-linear plots, the typical range for good fits between the model and cumulative number-based distributions was 1.9 fitted standard deviations less than the mean to 2.3 fitted standard deviations above the mean. Automated image capture, automated particle analysis and statistical evaluation of the data and fitting coefficients provide a framework for assessing nanoparticle size distributions using TEM for image acquisition. C1 [Rice, Stephen B.] Cabot Corp, Billerica, MA 01821 USA. [Chan, Christopher; Brown, Scott C.] Dupont Cent Res & Dev, Wilmington, DE 19880 USA. [Eschbach, Peter] Hewlett Packard Corp, Corvallis, OR USA. [Han, Li; Ensor, David S.] RTI Int, Nanotechnol Engn Technol Unit, Res Triangle Pk, NC 27709 USA. [Stefaniak, Aleksandr B.] NIOSH, Morgantown, WV 26505 USA. [Bonevich, John; Vladar, Andras E.; Walker, Angela R. Hight] NIST, Gaithersburg, MD 20899 USA. [Zheng, Jiwen] US FDA, Div Chem & Mat Sci, Silver Spring, MD 20993 USA. [Starnes, Catherine; Stromberg, Arnold] Univ Kentucky, Dept Stat, Lexington, KY 40506 USA. [Starnes, Catherine; Stromberg, Arnold] Univ Kentucky, Appl Stat Lab, Lexington, KY 40506 USA. [Ye, Jia; Grulke, Eric A.] Univ Kentucky, Lexington, KY 40506 USA. RP Rice, SB (reprint author), Cabot Corp, 157 Concord Rd, Billerica, MA 01821 USA. EM eric.grulke@uky.edu RI Hight Walker, Angela/C-3373-2009; Brown, Scott/A-7254-2008 OI Hight Walker, Angela/0000-0003-1385-0672; Brown, Scott/0000-0003-0138-474X FU Intramural CDC HHS [CC999999] NR 34 TC 10 Z9 10 U1 4 U2 29 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0026-1394 EI 1681-7575 J9 METROLOGIA JI Metrologia PD DEC PY 2013 VL 50 IS 6 BP 663 EP 678 DI 10.1088/0026-1394/50/6/663 PG 16 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA AA1BP UT WOS:000330831600012 PM 26361398 ER PT J AU Frush, D Denham, CR Goske, MJ Brink, JA Morin, RL Mills, TT Butler, PF McCollough, C Miller, DL AF Frush, Donald Denham, Charles R. Goske, Marilyn J. Brink, James A. Morin, Richard L. Mills, Thalia T. Butler, Priscilla F. McCollough, Cynthia Miller, Donald L. TI Radiation Protection and Dose Monitoring in Medical Imaging: A Journey From Awareness, Through Accountability, Ability and Action ... But Where Will We Arrive? SO JOURNAL OF PATIENT SAFETY LA English DT Review DE CT scan; radiation dose; image gently; computed tomography; children; radiation risk; radiation protection ID CANCER-RISK ESTIMATION; COMPUTED-TOMOGRAPHY; CT; EXPOSURE; CAMPAIGN AB Radiation awareness and protection of patients have been the fundamental responsibilities in diagnostic imaging since the discovery of x-rays late in 1895 and the first reports of radiation injury in 1896. In the ensuing years, there have been significant advancements in equipment that uses either x-rays to form images, such as fluoroscopy or computed tomography (CT), or the types of radiation emitted during nuclear imaging procedures (e.g., positron emission tomography [PET]). These advancements have allowed detailed and indispensable evaluation of a vast array of disorders. In fact, in 2001, CT and MRI were cited by physicians as the most significant medical innovations in the previous 3 decades. Rapid technological advancements in the last decade with CT, especially, have required imaging professionals to keep pace with increasingly complex technology to derive the maximum benefits of improved image acquisition and display techniques, in essence, the improved quality of the examination. It has also been challenging to fulfill the fundamental responsibilities of safety during this period of rapid growth (e.g., radiation protection, management of the risk of additional interventions driven by incidental findings, performing studies that were not indicated). The purpose of this paper is to define critical issues pertinent to ensuring patient safety through the appropriate assessment, recording, monitoring, and reporting of the radiation dose from CT. C1 [Frush, Donald] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. [Denham, Charles R.] TMIT, Austin, TX USA. [Goske, Marilyn J.] Childrens Hosp Med Ctr, Cincinnati, OH USA. [Brink, James A.] Massachusetts Gen Hosp, Dept Diagnost Radiol, Boston, MA 02114 USA. [Morin, Richard L.] Mayo Clin Jacksonville, Dept Radiol, Jacksonville, FL 32224 USA. [Mills, Thalia T.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Butler, Priscilla F.] Amer Coll Radiol, Dept Qual & Safety, Reston, VA USA. [Miller, Donald L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Frush, D (reprint author), Duke Univ, Med Ctr, McGovern Davison Childrens Hlth Ctr 1905, Div Pediat Radiol, Erwin Rd, Durham, NC 27710 USA. EM donald.frush@duke.edu NR 58 TC 7 Z9 8 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1549-8417 EI 1549-8425 J9 J PATIENT SAF JI J. Patient Saf. PD DEC PY 2013 VL 9 IS 4 BP 232 EP 238 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 300GA UT WOS:000330451200008 PM 24257067 ER PT J AU Wong, KS Nguyen, JN White, T Menefee, SA Walter, AJ Krulewitch, CJ Anderson-Smits, CT Jakus-Waldman, SM AF Wong, Keri S. Nguyen, John N. White, Terry Menefee, Shawn A. Walter, Andrew J. Krulewitch, Cara J. Anderson-Smits, Colin T. Jakus-Waldman, Sharon M. TI Adverse Events Associated With Pelvic Organ Prolapse Surgeries That Use Implants SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID RANDOMIZED-CONTROLLED-TRIAL; ABDOMINAL RECONSTRUCTIVE SURGERY; SACROSPINOUS LIGAMENT SUSPENSION; ANTERIOR VAGINAL PROLAPSE; TERM OUTCOME EVALUATION; SUPPORT DEFECTS; TRANSVAGINAL MESH; RISK-FACTORS; SURGICAL REPAIR; SEXUAL FUNCTION AB OBJECTIVE: To estimate the rate of vaginal implant exposure associated with biologic grafts and permanent mesh used for pelvic organ prolapse (POP) surgery, to describe treatments used for these complications, and to estimate response rates to these treatments. The secondary aims were to describe the operative and perioperative complications. METHODS: This was a retrospective analysis of female members of Kaiser Permanente Southern and Northern California and Hawaii who underwent POP surgeries with biologic grafts and permanent mesh between September 2008 and May 2010. Inpatient and outpatient electronic medical records were reviewed for postoperative adverse events. RESULTS: During the 21-month period, 1,282 women, mean age of 62 years (+/- 10 standard deviation), median parity of 3 (interquartile range 2-4), and median body mass index of 28 (interquartile range 24-30) underwent prolapse repairs with 1,484 implants with a mean follow-up time of 358 days (+/- 276 standard deviation). Vaginal exposures occurred more often with permanent mesh (53/847 [6%]) than biologic grafts (10/637 [1.6%]) (P<.001). Resolution of vaginal exposure after the first treatment occurred in 24 of 63 (38%), whereas 39 of 63 (62%) required multiple treatments. Surgical excision was performed in 20 of 63 (32%) exposures. Permanent mesh exposures were more likely to require surgical excision (20/53 [38%]) than biologic graft exposures (zero of 10) (P=.02). CONCLUSION: Vaginal exposure occurred more frequently with permanent mesh than biologic graft, may require multiple treatments, and occasionally require surgical excision. C1 Kaiser Permanente, Dept Obstet & Gynecol, Downey, CA USA. Kaiser Permanente, Dept Obstet & Gynecol, Roseville, CA USA. Kaiser Permanente, Dept Obstet & Gynecol, Honolulu, HI USA. US FDA, Div Epidemiol, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Nguyen, JN (reprint author), Kaiser Fdn Hosp, Dept Obstet & Gynecol, So Calif Permanente Med Grp, 9449 E Imperial Highway,Suite C327, Downey, CA 90242 USA. EM John.N.Nguyen@kp.org FU U.S. Food and Drug Administration FX Funding provided by the U.S. Food and Drug Administration. NR 23 TC 2 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 2013 VL 122 IS 6 BP 1239 EP 1245 DI 10.1097/AOG.0000000000000008 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 300FV UT WOS:000330450700014 PM 24201675 ER PT J AU Moro, PL Museru, OI Broder, K Cragan, J Zheteyeva, Y Tepper, N Revzina, N Lewis, P Arana, J Barash, F Kissin, D Vellozzi, C AF Moro, Pedro L. Museru, Oidda I. Broder, Karen Cragan, Janet Zheteyeva, Yenlik Tepper, Naomi Revzina, Natalia Lewis, Paige Arana, Jorge Barash, Faith Kissin, Dmitry Vellozzi, Claudia TI Safety of Influenza A (H1N1) 2009 Live Attenuated Monovalent Vaccine in Pregnant Women SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID IMMUNIZATION PRACTICES ACIP; ADVISORY-COMMITTEE; UNITED-STATES; FETAL-DEATH; RECOMMENDATIONS; PREVENTION; COHORT; RISK AB OBJECTIVE: To characterize maternal and infant outcomes for pregnant women who received live H1N1 influenza vaccine and had no reported adverse events. METHODS: We identified Vaccine Adverse Event Reporting System reports, which described receipt of live H1N1 vaccine during pregnancy without an indication of an adverse event at the time of the report during October 2009 to June 2010. We reviewed the initial reports and obtained pregnancy outcome and infant data through 6 months of age from medical records. We reviewed the numbers and characteristics of pregnancy complications and infant outcomes including major birth defects and medically important infant conditions. Rates of spontaneous abortion, preterm birth, and major birth defects and their 95% confidence intervals were calculated. RESULTS: The Vaccine Adverse Event Reporting System received 113 reports stating receipt of live H1N1 vaccine during pregnancy with no adverse events reported. We obtained follow-up maternal records on 95 of the 113 (84%) live H1N1 reports (40.2% were vaccinated in the first trimester) and found: 87 live births (two twin pregnancies) and no maternal deaths occurred. Number and rates of pregnancy-specific adverse events included: 10 (10.5%, 5.8-18.3) spontaneous abortions; four (4.7%, 1.8-11.4) preterm deliveries at 35-36 weeks of gestation; three (3.4%, 1.2-9.7) infants had one or more major birth defects noted at birth: one cleft palate, one cleft lip, and one microtia (underdeveloped or absent external ear). Seven neonates and infants were hospitalized for medically important conditions. One infant death occurred in a 2.5-month-old boy as a result of pertussis. CONCLUSION: Rates of spontaneous abortion, preterm birth, and major birth defects in pregnant women who received live H1N1 vaccine were similar to or lower than published background rates. No concerning patterns of medical conditions in infants were identified. C1 Ctr Dis Control & Prevent, Immunizat Safety Off,Natl Ctr Birth Defects & Dev, Div Healthcare Qual Promot,Div Birth Defects & De, Natl Ctr Emerging & Zoonot Infect Dis,Birth Defec, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Womens Hlth & Fertil Branch, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. Emory Sch Med, Dept Pediat, Atlanta, GA USA. US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Silver Spring, MD USA. RP Moro, PL (reprint author), Ctr Dis Control & Prevent, Immunizat Safety Off, Div Healthcare Qual Promot, 1600 Clifton Rd,MS D26, Atlanta, GA 30333 USA. EM pmoro@cdc.gov FU Centers for Disease Control and Prevention; U.S. Food and Drug Administration FX Funded by the Centers for Disease Control and Prevention and the U.S. Food and Drug Administration. NR 30 TC 18 Z9 18 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 2013 VL 122 IS 6 BP 1271 EP 1278 DI 10.1097/AOG.0000000000000010 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 300FV UT WOS:000330450700018 PM 24201689 ER PT J AU Hampp, C Kang, EM Borders-Hemphill, V AF Hampp, Christian Kang, Elizabeth M. Borders-Hemphill, Vicky TI Use of Prescription Antiobesity Drugs in the United States SO PHARMACOTHERAPY LA English DT Article DE antiobesity drugs; utilization; duration; phentermine; orlistat; sibutramine ID OBESITY; TRENDS AB STUDY OBJECTIVE To examine national trends in prescription antiobesity drug use in the United States. DESIGN Data analysis. DATA SOURCE The IMS Health Vector One National and Total Patient Tracker and Encuity Research Treatment Answers databases, the Source Healthcare Analytics Source Lx database, and IMS LifeLink database. MEASUREMENTS AND MAIN RESULTS National drug use estimates from 1991-2011 were extracted from the IMS Health Vector One National database, and patient characteristics from 2008-2011 were extracted from the Vector One Total Patient Tracker and Encuity Research Treatment Answers databases. The Source Healthcare Analytics Source Lx database was used to examine duration of antiobesity drug use from 2002-2011, with a sensitivity analysis performed using the IMS LifeLink database. In 2011, approximately 2.74 million patients used antiobesity drugs, predominantly phentermine (2.43 million patients). The use of prescription orlistat and sibutramine was relatively uncommon. Eighty-five percent of antiobesity drug users were female, 62% were aged 17-44 years, and 4.5% had a body mass index of <= 24.9 kg/m(2). Duration of use was generally short and most patients only had one episode of antiobesity drug use during the observation period. The longest episode of use was 30 days or less in 47-58% of patients. Approximately one quarter of the patients used antiobesity drugs for longer than 90 days, including phentermine and other amphetamine congeners whose labels recommend short-term use, not exceeding "a few weeks." Only 1.3-4.2% of antiobesity drug users used them for longer than 1 year. Concomitant use of two or more prescription weight-loss drugs was generally uncommon, although phentermine was dispensed during 13-16% of benzphetamine, diethylpropion, or phendimetrazine episodes of use. CONCLUSION Phentermine dominated the prescription weight-loss market. Despite the indication of short-term use for amphetamine congeners, duration of use was similar to other antiobesity drugs. Nevertheless, the reasons for and implications of the limited duration of use observed with all prescription antiobesity drugs deserve further investigation. C1 [Hampp, Christian; Kang, Elizabeth M.] US FDA, Div Epidemiol 1, Off Pharmacovigilance & Epidemiol, Off Surveillance & Epidemiol,Ctr Drug Evaluat & R, Silver Spring, MD 20993 USA. [Borders-Hemphill, Vicky] US FDA, Div Medicat Error Prevent & Anal, Off Medicat Error Prevent & Risk Management, Off Surveillance & Epidemiol,Ctr Drug Evaluat & R, Silver Spring, MD 20993 USA. RP Hampp, C (reprint author), US FDA, Div Epidemiol 1, Off Pharmacovigilance & Epidemiol, Off Surveillance & Epidemiol,Ctr Drug Evaluat & R, Silver Spring, MD 20993 USA. EM Christian.hampp@fda.hhs.gov FU Intramural FDA HHS [FD999999] NR 14 TC 25 Z9 25 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-0008 EI 1875-9114 J9 PHARMACOTHERAPY JI Pharmacotherapy PD DEC PY 2013 VL 33 IS 12 BP 1299 EP 1307 DI 10.1002/phar.1342 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 297HQ UT WOS:000330246900011 PM 24019195 ER PT J AU Zhang, GD Thau, E Brown, EW Hammack, TS AF Zhang, Guodong Thau, Eve Brown, Eric W. Hammack, Thomas S. TI Comparison of a novel strategy for the detection and isolation of Salmonella in shell eggs with the Food and Drug Administration Bacteriological Analytical Manual method SO POULTRY SCIENCE LA English DT Article DE Salmonella; broth; detection; isolation; egg ID REAL-TIME PCR; RAPPAPORT-VASSILIADIS MEDIUM; LOW MICROBIAL LOAD; RAPID DETECTION; ENTERITIDIS; RECOVERY; SPP.; GROWTH; SYSTEM; POOLS AB The current FDA Bacteriological Analytical Manual (BAM) method for the detection of Salmonella in eggs requires 2 wk to complete. The objective of this project was to improve the BAM method for the detection and isolation of Salmonella in whole shell eggs. A novel protocol, using 1,000 g of liquid eggs for direct preenrichment with 2 L of tryptic soy broth (TSB) followed by enrichment using Rappaport-Vassiliadis and Tetrathionate broths, was compared with the standard BAM method, which requires 96 h room temperature incubation of whole shell egg samples followed by preenrichment in TSB supplemented with FeSO4. Four Salmonella ser. Enteritidis (4 phage types) and one Salmonella ser. Heidelberg isolates were used in the study. Bulk inoculated pooled liquid eggs, weighing 52 or 56 kg (approximately 1,100 eggs) were used in each trial. Twenty 1,000-g test portions were withdrawn from the pooled eggs for both the alternative and the reference methods. Test portions were inoculated with Salmonella at 1 to 5 cfu/1,000 g eggs. Two replicates were performed for each isolate. In the 8 trials conducted with Salmonella ser. Enteritidis, the alternative method was significantly (P < 0.05) more productive than the reference method in 3 trials, and significantly (P < 0.05) less productive than the reference method in 1 trial. There were no significant (P < 0.05) differences between the 2 methods for the other 4 trials. For Salmonella ser. Heidelberg, combined data from 2 trials showed the alternative method was significantly (P < 0.05) more efficient than the BAM method. We have concluded that the alternative method, described herein, has the potential to replace the current BAM culture method for detection and isolation of Salmonella from shell eggs based on the following factors: 1) the alternative method is 4 d shorter than the reference method; 2) it uses regular TSB instead of the more complicated TSB supplemented with FeSO4; and 3) it was equivalent or superior to the reference method in 9 out of 10 trials for the detection of Salmonella in shell eggs. C1 [Zhang, Guodong; Thau, Eve; Brown, Eric W.; Hammack, Thomas S.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Zhang, GD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Guodong.Zhang@fda.hhs.gov NR 39 TC 0 Z9 0 U1 1 U2 11 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874-9604 USA SN 0032-5791 EI 1525-3171 J9 POULTRY SCI JI Poult. Sci. PD DEC PY 2013 VL 92 IS 12 BP 3266 EP 3274 DI 10.3382/ps.2013-03380 PG 9 WC Agriculture, Dairy & Animal Science SC Agriculture GA 301IR UT WOS:000330526500025 PM 24235238 ER PT J AU Lu, YH Sun, JC Petrova, K Yang, X Greenhaw, J Salminen, WF Beger, RD Schnackenberg, LK AF Lu, Yihong Sun, Jinchun Petrova, Katya Yang, Xi Greenhaw, James Salminen, William F. Beger, Richard D. Schnackenberg, Laura K. TI Metabolomics evaluation of the effects of green tea extract on acetaminophen-induced hepatotoxicity in mice SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Green tea extract; Acetaminophen; Hepatotoxicity; Metabolic profiling; Metabolomics ID MITOCHONDRIAL PERMEABILITY TRANSITION; CHROMATOGRAPHY-MASS SPECTROMETRY; DIETARY-SUPPLEMENT HEPATOTOXICITY; NITRIC-OXIDE; OXIDATIVE STRESS; BILE-ACIDS; UNITED-STATES; CELL-DEATH; URIC-ACID; RAT-LIVER AB Green tea has been purported to have beneficial health effects including protective effects against oxidative stress. Acetaminophen (APAP) is a widely used analgesic drug that can cause acute liver injury in overdose situations. These studies explored the effects of green tea extract (GTE) on APAP-induced hepatotoxicity in liver tissue extracts using ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry and nuclear magnetic resonance spectroscopy. Mice were orally administered GTE, APAP or GTE and APAP under three scenarios. APAP alone caused a high degree of hepatocyte necrosis associated with increases in serum transaminases and alterations in multiple metabolic pathways. The time of GTE oral administration relative to APAP either protected against or potentiated the APAP-induced hepatotoxicity. Dose dependent decreases in histopathology scores and serum transaminases were noted when GTE was administered prior to APAP; whereas, the opposite occurred when GTE was administered after APAP. Similarly, metabolites altered by APAP alone were less changed when GTE was given prior to APAP. Significantly altered pathways included fatty acid metabolism, glycerophospholipid metabolism, glutathione metabolism, and energy pathways. These studies demonstrate the complex interaction between GTE and APAP and the need to employ novel analytical strategies to understand the effects of dietary supplements on pharmaceutical compounds. Published by Elsevier Ltd. C1 [Lu, Yihong; Sun, Jinchun; Petrova, Katya; Yang, Xi; Greenhaw, James; Salminen, William F.; Beger, Richard D.; Schnackenberg, Laura K.] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Schnackenberg, LK (reprint author), US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson Labs, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Laura.Schnackenberg@fda.hhs.gov NR 70 TC 12 Z9 17 U1 8 U2 44 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 2013 VL 62 BP 707 EP 721 DI 10.1016/j.fct.2013.09.025 PG 15 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 293GW UT WOS:000329960400090 PM 24080264 ER PT J AU Teeguarden, J Hanson-Drury, S Fisher, JW Doerge, DR AF Teeguarden, Justin Hanson-Drury, Sesha Fisher, Jeffrey W. Doerge, Daniel R. TI Are typical human serum BPA concentrations measurable and sufficient to be estrogenic in the general population? SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Review DE BPA; Epidemiology; Toxicity; Estrogenic; Biomonitoring ID BISPHENOL-A CONCENTRATIONS; SPRAGUE-DAWLEY RATS; ENDOCRINE-DISRUPTING CHEMICALS; TANDEM MASS-SPECTROMETRY; PERFORMANCE LIQUID-CHROMATOGRAPHY; IN-VITRO FERTILIZATION; HUMAN URINE; RHESUS-MONKEYS; REPRODUCTIVE TOXICITY; BIOLOGICAL SAMPLES AB Mammalian estrogen receptors modulate many physiological processes. Chemicals with structural features similar to estrogens can interact with estrogen receptors to produce biological effects similar to those caused by endogenous estrogens in the body. Bisphenol A (BPA) is a structural analogue of estrogen that binds to estrogen receptors. Exposure to BPA in humans is virtually ubiquitous in industrialized societies, but BPA is rapidly detoxified by metabolism and does not accumulate in the body. Whether or not serum concentrations of BPA in humans are sufficiently high to disrupt normal estrogen-related biology is the subject of intense political and scientific debate. Here we show a convergence of robust methods for measuring or calculating serum concentrations of BPA in humans from 93 published studies of more than 30,000 individuals in 19 countries across all life stages. Typical serum BPA concentrations are orders of magnitude lower than levels measurable by modern analytical methods and below concentrations required to occupy more than 0.0009% of Type II Estrogen Binding Sites, GPR30, ER alpha or ER beta receptors. Occupancies would be higher, but <= 0.04%, for the highest affinity receptor, ERR gamma. Our results show limited or no potential for estrogenicity in humans, and question reports of measurable BPA in human serum. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Teeguarden, Justin; Hanson-Drury, Sesha] Pacific Norwest Natl Lab, Richland, WA 99352 USA. [Fisher, Jeffrey W.; Doerge, Daniel R.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Teeguarden, J (reprint author), 902 Battelle Blvd, Richland, WA 99352 USA. EM jt@pnl.gov OI Teeguarden, Justin/0000-0003-3817-4391 FU U.S. EPA [R83386701] FX The authors would like to thank the U.S. EPA for providing funding for this work under the STAR program, grant R83386701. The authors would also like to thank Dr. Daniel Naiman, Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD for providing the exposure data for women of child-bearing age derived from NHANES data. The authors are also grateful for the graphics support provided by Mr. Cortland Johnson of the Pacific Northwest National Laboratory. The views expressed in this article do not necessarily reflect those of the U.S. Food and Drug Administration. NR 117 TC 33 Z9 33 U1 4 U2 37 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 2013 VL 62 BP 949 EP 963 DI 10.1016/j.fct.2013.08.001 PG 15 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 293GW UT WOS:000329960400118 PM 23959105 ER PT J AU Rahkovsky, I Lin, BH Lin, CTJ Lee, JY AF Rahkovsky, Ilya Lin, Biing-Hwan Lin, Chung-Tung Jordan Lee, Jonq-Ying TI Effects of the Guiding Stars Program on purchases of ready-to-eat cereals with different nutritional attributes SO FOOD POLICY LA English DT Article DE Nutrition information; Front-of-package nutrition labeling; Cereal demand; Guiding Stars Program ID FOOD LABELS; INFORMATION; CONSUMERS; SPACE AB Over the past decade, the food industry has increased its use of front-of-package and shelf-tag nutrition labeling designed to present key nutritional aspects and characteristics of food products. One such system is the Guiding Stars Program (TM) (GSP), which uses an algorithm to score the nutritional values of food products from one to three stars, where more stars mean more nutritious. We studied how the introduction of the GSP in one supermarket chain affected the demand for ready-to-eat cereals. We estimated the demand for cereals and measured the effect using a treatment-control approach. We found that the GSP significantly increased the demand for cereals that GSP considers more nutritious at the expense of cereals that GSP considers less nutritious. Published by Elsevier Ltd. C1 [Rahkovsky, Ilya; Lin, Biing-Hwan] USDA, Econ Res Serv, Washington, DC USA. [Lin, Chung-Tung Jordan] US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. [Lee, Jonq-Ying] Univ Florida, Gainesville, FL 32611 USA. RP Rahkovsky, I (reprint author), 355 E St SW, Washington, DC 20024 USA. EM irahkovsky@ers.usda.gov NR 33 TC 11 Z9 11 U1 1 U2 16 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0306-9192 EI 1873-5657 J9 FOOD POLICY JI Food Policy PD DEC PY 2013 VL 43 BP 100 EP 107 DI 10.1016/j.foodpol.2013.08.013 PG 8 WC Agricultural Economics & Policy; Economics; Food Science & Technology; Nutrition & Dietetics SC Agriculture; Business & Economics; Food Science & Technology; Nutrition & Dietetics GA 285SA UT WOS:000329414100010 ER PT J AU Winterstein, AG Knox, CA Kubilis, P Hampp, C AF Winterstein, Almut G. Knox, Caitlin A. Kubilis, Paul Hampp, Christian TI Appropriateness of Age Thresholds for Respiratory Syncytial Virus Immunoprophylaxis in Moderate-Preterm Infants A Cohort Study SO JAMA PEDIATRICS LA English DT Article ID WEEKS GESTATIONAL-AGE; INFECTION REQUIRING HOSPITALIZATION; INTENSIVE-CARE-UNIT; PREMATURE-INFANTS; RISK-FACTORS; PREDICT HOSPITALIZATION; COMPLETED WEEKS; BORN; CHILDREN; BRONCHIOLITIS AB IMPORTANCE Recommendations concerning the appropriate age threshold for respiratory syncytial virus (RSV) prophylaxis in moderate-preterm infants are highly debated. OBJECTIVE To determine the age at which moderate-preterm infants' risk of RSV hospitalization has decreased to the risk observed in low-risk term infants. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of Florida and Texas Medicaid fee-for-service billing records matched to birth certificates from Medicaid beneficiaries aged 0 to 12 months with a sibling younger than 5 years and without other indications for RSV prophylaxis between January 1, 1999, and December 31, 2004. EXPOSURES For each state, we used discrete time survival analysis to develop age trend models for RSV hospitalizations for 2 groups: moderate-preterm infants (32-34 weeks' gestational age) and term infants (37-41 weeks' gestational age). MAIN OUTCOMES AND MEASURES Age at which preterm infants' risk of RSV hospitalization equaled the risk for term infants at age 1 month. RESULTS Our cohort included 247 566 eligible infants with 5322 RSV hospitalizations. Preterm status doubled the risk for RSV hospitalization in both Florida (odds ratio = 2.41; 95% CI, 1.85-3.12) and Texas (odds ratio = 1.94; 95% CI, 1.64-2.30). Preterm infants' risk of RSV hospitalization was similar to that for 1-month-old term infants at ages 4.2 months (95% CI, 2.5-5.7) in Florida and 4.5 months (95% CI, 2.8-6.4) in Texas. CONCLUSIONS AND RELEVANCE The age at which moderate-preterm infants showed RSV hospitalization risk similar to their healthy term counterparts supports the more restrictive age thresholds in RSV immunoprophylaxis recommendations. Further studies are warranted to investigate the age-dependent risk of RSV hospitalization in other RSV risk groups. C1 [Winterstein, Almut G.] Univ Florida, Dept Epidemiol, Gainesville, FL 32610 USA. [Winterstein, Almut G.; Knox, Caitlin A.; Kubilis, Paul] Univ Florida, Dept Pharmaceut Outcomes & Policy, Gainesville, FL 32610 USA. [Hampp, Christian] US FDA, Div Epidemiol, Off Pharmacovigilance & Epidemiol, Off Surveillance & Epidemiol,Ctr Drug Evaluat & R, Silver Spring, MD USA. RP Winterstein, AG (reprint author), Univ Florida, Coll Pharm, Dept Pharmaceut Outcomes & Policy, HPNP Bldg,1225 Ctr Dr,POB 100496, Gainesville, FL 32610 USA. EM almut@ufl.edu RI winterstein, Almut/A-3017-2014 OI winterstein, Almut/0000-0002-6518-5961 FU Florida Agency of Healthcare Administration; American Foundation for Pharmaceutical Education fellowship FX This study was supported in part by a grant from the Florida Agency of Healthcare Administration and was conducted in collaboration with the Florida Center for Medicaid and the Uninsured, University of Florida. Ms Knox was supported by an American Foundation for Pharmaceutical Education fellowship and the Mary K. Owens Fellowship for Healthcare Innovation from the University of Florida. NR 49 TC 20 Z9 20 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD DEC PY 2013 VL 167 IS 12 BP 1118 EP 1124 DI 10.1001/jamapediatrics.2013.2636 PG 7 WC Pediatrics SC Pediatrics GA 291QY UT WOS:000329845300010 PM 24126903 ER PT J AU Minor, T AF Minor, Travis TI An investigation into the effect of type I and type II diabetes duration on employment and wages SO ECONOMICS & HUMAN BIOLOGY LA English DT Article DE Diabetes; Labor supply; Wages; Panel data ID WORK PRODUCTIVITY; HEALTH; IMPACT; PREVALENCE; RISK AB Using data from the National Longitudinal Survey of Youth 1979, the current study examines the effect of type I and type II diabetes on employment status and wages. The results suggest that both the probability of employment and wages are negatively related to the number of years since the initial diagnosis of diabetes. Moreover, the effect of diabetes duration on the probability of employment appears to be nonlinear, peaking around 16 years for females and 10 years for males. A similar negative effect on wages is found only in male diabetics. Finally, the results suggest that failure to distinguish between type I and type II diabetics may lead to some counterintuitive results. Published by Elsevier B.V. C1 [Minor, Travis] US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. RP Minor, T (reprint author), FDA CFSAN, CPK1 HFS 020,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Travis.Minor@fda.hhs.gov OI Minor, Travis/0000-0002-5297-7695 NR 21 TC 6 Z9 6 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-677X EI 1873-6130 J9 ECON HUM BIOL JI Econ. Hum. Biol. PD DEC PY 2013 VL 11 IS 4 BP 534 EP 544 DI 10.1016/j.ehb.2013.04.004 PG 11 WC Economics; Public, Environmental & Occupational Health SC Business & Economics; Public, Environmental & Occupational Health GA 283RR UT WOS:000329265200013 PM 23659822 ER PT J AU Guettier, JM Lungu, A Goodling, A Cochran, C Gorden, P AF Guettier, Jean-Marc Lungu, Andreea Goodling, Anne Cochran, Craig Gorden, Phillip TI The Role of Proinsulin and Insulin in the Diagnosis of Insulinoma: A Critical Evaluation of the Endocrine Society Clinical Practice Guideline SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ISLET CELL TUMORS; CIRCULATING INSULIN; PLASMA PROINSULIN; COMPONENT AB Context: An end of fast insulin >= 3 mu IU/mL and a proinsulin concentration >= 5 pmol/L have been suggested as useful cutoffs for the diagnosis of insulinoma. Objective: The main objective was to evaluate the diagnostic performance of an end of fast insulin concentration >= 3 mu IU/mL and an end of fast proinsulin concentration >= 5 pmol/L. Design: The design was a case-control series. Setting: The setting was a tertiary-care center. Patients: Fifty-six subjects with a positive 48-hour supervised fast had an insulinoma between June 2000 and April 2011. During this same time period, a diagnosis of insulinoma was excluded in 29 subjects who underwent a supervised fast. Intervention: 48-hour supervised fast. Main Outcome Measure: The main outcome measures were serum insulin concentration and plasma proinsulin concentration. Results: Ninety-one percent of the patients with an insulinoma had a measured insulin concentration >= 5 mu IU/mL at the end of fast. The sensitivity increased to 98% if the threshold to define inadequate insulin suppression was lowered to >= 3 mu IU/mL. The median (interquartile range) end of fast proinsulin was 100 (53-270) pmol/L for cases and 6.8 (4.2-12.0) pmol/L for controls. An end of fast proinsulin value of >5 pmol/L could not distinguish cases from controls (59% false positive rate). All patients with an insulinoma (sensitivity 100%) and none of the control subject (specificity 100%) had end of fast proinsulin concentration >= 27 pmol/L. Conclusions: Using a current insulin assay 9% of insulinoma cases end the supervised fast with an insulin concentration below 5 mu IU/mL. Inadequate insulin suppression defined using a threshold of >= 3 mu IU/mL increases the sensitivity of the test. The value of the proinsulin test lies in its unique ability to distinguish cases from controls. A proinsulin concentration of >= 22 pmol/L best discriminates cases from controls. Reliance on an end of fast proinsulin cutoff value of 5 pmol/L does not augment sensitivity but greatly reduces specificity of the test. C1 [Guettier, Jean-Marc; Lungu, Andreea; Goodling, Anne; Cochran, Craig; Gorden, Phillip] NIDDK, NIH, Bethesda, MD 20892 USA. [Guettier, Jean-Marc] US FDA, Div Metab & Endocrinol Prod, Silver Spring, MD 20903 USA. RP Guettier, JM (reprint author), Bldg 10 CRC,Room 6-5952,10 Ctr Dr, Bethesda, MD 20892 USA. EM Jean-Marc.Guettier@fda.hhs.gov FU National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health. NR 16 TC 14 Z9 15 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2013 VL 98 IS 12 BP 4752 EP 4758 DI 10.1210/jc.2013-2182 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 272RF UT WOS:000328477200047 PM 24081736 ER PT J AU Li, BG Chen, JQ AF Li, Baoguang Chen, Jin-Qiang TI Development of a sensitive and specific qPCR assay in conjunction with propidium monoazide for enhanced detection of live Salmonella spp. in food SO BMC MICROBIOLOGY LA English DT Article DE Salmonella; qPCR; Propidium monoazide; Live cells; invA gene ID REAL-TIME PCR; POLYMERASE-CHAIN-REACTION; UNITED-STATES; SELECTIVE DETECTION; REFERENCE COLLECTION; FOODBORNE ILLNESS; QUANTITATIVE PCR; AMPLICON LENGTH; RAPID DETECTION; AMPLIFICATION AB Background: Although a variety of methodologies are available for detection of Salmonella, sensitive, specific, and efficient methods are urgently needed for differentiation of live Salmonella cells from dead cells in food and environmental samples. Propidium monoazide (PMA) can preferentially penetrate the compromised membranes of dead cells and inhibit their DNA amplification, however, such inhibition has been reported to be incomplete by some studies. In the present study, we report an efficient qPCR assay targeting a conserved region of the invA gene of Salmonella in conjunction with PMA treatment for detection of DNA from live Salmonella cells in food samples. Results: We investigated the relationship between amplicon length and inhibitory effect of PMA treatment to prevent DNA amplification from dead cells while allowing for DNA amplification from live cells, and found that the two factors are well correlated with each other. An amplicon that is 130 bp in length was determined to be optimal for PMA treatment and was selected for further PMA-qPCR assay development. A PMA-qPCR assay was established by utilizing this amplicon and adopting a modified PMA-treatment procedure. The PMA-qPCR assay provided excellent inhibition of DNA amplification from dead cells (a 17-C-T-value, or 128,000-fold reduction) while only a slight DNA amplification difference (0.5 C-T value) was noted between the PMA-treated and untreated live cells. This assay has been validated through stringent inclusivity and exclusivity studies using a large number of (n = 167) Salmonella, including all strains of SARA and SARB collections, and non-Salmonella strains (n = 36). This PMA-qPCR assay is capable of detecting live Salmonella cells in live/dead cell mixtures, or 30 CFU/g live Salmonella cells from enriched spiked spinach samples as early as 4 h. Conclusions: A 130-bp amplicon in invA gene was demonstrated to be optimal for PMA treatment for selective detection of live Salmonella cells by PCR. This PMA-qPCR assay provides a sensitive, specific, and efficient method for detecting live Salmonella cells in foods and environmental samples and may have an impact on the accurate microbiological monitoring of Salmonella in foods and environment samples. C1 [Li, Baoguang; Chen, Jin-Qiang] US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Li, BG (reprint author), US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. EM baoguang.li@fda.hhs.gov NR 45 TC 13 Z9 13 U1 2 U2 22 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 DEC 1 PY 2013 VL 13 AR 273 DI 10.1186/1471-2180-13-273 PG 13 WC Microbiology SC Microbiology GA 277ZJ UT WOS:000328857500001 PM 24289661 ER PT J AU Stevenson, L Garofolo, F DeSilva, B Dumont, I Martinez, S Rocci, M Amaravadi, L Brudny-Kloeppel, M Musuku, A Booth, B Dicaire, C Wright, L Mayrand-Provencher, L Losauro, M Gouty, D Arnold, M Bansal, S Dudal, S Dufield, D Duggan, J Evans, C Fluhler, E Fraser, S Gorovits, B Haidar, S Hayes, R Ho, S Houghton, R Islam, R Jenkins, R Katori, N Kaur, S Kelley, M Knutsson, M Lee, J Liu, HL Lowes, S Ma, M Mikulskis, A Myler, H Nicholson, B Olah, T Ormsby, E Patel, S Pucci, V Ray, C Schultz, G Shih, J Shoup, R Simon, C Song, A Neto, JT Theobald, V Thway, T Wakelin-Smith, J Wang, J Wang, LX Welink, J Whale, E Woolf, E Xu, R AF Stevenson, Lauren Garofolo, Fabio DeSilva, Binodh Dumont, Isabelle Martinez, Suzanne Rocci, Mario Amaravadi, Lakshmi Brudny-Kloeppel, Margarete Musuku, Adrien Booth, Brian Dicaire, Catherine Wright, Laura Mayrand-Provencher, Laurence Losauro, Mike Gouty, Dominique Arnold, Mark Bansal, Surendra Dudal, Sherri Dufield, Dawn Duggan, Jeff Evans, Christopher Fluhler, Eric Fraser, Stephanie Gorovits, Boris Haidar, Sam Hayes, Roger Ho, Stacy Houghton, Richard Islam, Rafiqul Jenkins, Rand Katori, Noriko Kaur, Surinder Kelley, Marian Knutsson, Magnus Lee, Jean Liu, Hanlan Lowes, Steve Ma, Mark Mikulskis, Alvydas Myler, Heather Nicholson, Bob Olah, Timothy Ormsby, Eric Patel, Shefali Pucci, Vincenzo Ray, Chad Schultz, Gary Shih, Judy Shoup, Ronald Simon, Craig Song, An Neto, Joao Tavares Theobald, Valerie Thway, Theingi Wakelin-Smith, Jason Wang, Jian Wang, Laixin Welink, Jan Whale, Emma Woolf, Eric Xu, Raymond TI 2013 White Paper on recent issues in bioanalysis: 'hybrid' - the best of LBA and LCMS SO BIOANALYSIS LA English DT Article ID VALIDATION GROUP WORKSHOP; GLOBAL CRO COUNCIL; REGULATED BIOANALYSIS; Q-TOF; RECOMMENDATIONS; ASSAYS; BIOTHERAPEUTICS; QUANTIFICATION; CALIBRATION; CHALLENGES AB The 2013 7th Workshop on Recent Issues in Bioanalysis was held in Long Beach, California, USA, where close to 500 professionals from pharmaceutical and biopharmaceutical companies, CROs and regulatory agencies convened to discuss current topics of interest in bioanalysis. These hot' topics, which covered both small and large molecules, were the starting point for fruitful exchanges of knowledge, and sharing of ideas among speakers, panelists and attendees. The discussions led to specific recommendations pertinent to bioanalytical science. Such as the previous editions, this 2013 White Paper addresses important bioanalytical issues and provides practical answers to the topics presented, discussed and agreed upon by the global bioanalytical community attending the 7th Workshop on Recent Issues in Bioanalysis. C1 [Stevenson, Lauren; Amaravadi, Lakshmi; Mikulskis, Alvydas] Biogen Idec Inc, Cambridge, MA USA. [Garofolo, Fabio; Dumont, Isabelle; Martinez, Suzanne; Dicaire, Catherine; Mayrand-Provencher, Laurence] Algorithme Pharma Inc, Montreal, PQ H7V 4B3, Canada. [DeSilva, Binodh; Arnold, Mark; Myler, Heather; Olah, Timothy; Wang, Jian] Bristol Myers Squibb Co, Princeton, NJ USA. [Rocci, Mario] ICON Dev Solut, Whitesboro, NY USA. [Brudny-Kloeppel, Margarete] Bayer Pharma AG, Berlin, Germany. [Musuku, Adrien] Pharmascience, Montreal, PQ, Canada. [Booth, Brian; Haidar, Sam] US FDA, CDER, Silver Spring, MD USA. [Wright, Laura; Losauro, Mike; Gouty, Dominique] Intertek, San Diego, CA USA. [Bansal, Surendra] Hoffmann La Roche, Nutley, NJ USA. [Dudal, Sherri] Hoffmann La Roche AG, Basel, Switzerland. [Dufield, Dawn; Gorovits, Boris] Pfizer, Andover, MA USA. [Duggan, Jeff] Boehringer Ingelheim GmbH & Co KG, Ridgefield, CT USA. [Evans, Christopher] GlaxoSmithKline, King Of Prussia, PA USA. [Fluhler, Eric] Pfizer, Pearl River, NY USA. [Fraser, Stephanie] Pfizer, Groton, CT USA. [Hayes, Roger] MPI Res, Mattawan, MI USA. [Ho, Stacy; Liu, Hanlan] Sanofi, Waltham, MA USA. [Houghton, Richard] Quotient Biores, Fordham, England. [Islam, Rafiqul] Celerion, Lincoln, NE USA. [Jenkins, Rand; Nicholson, Bob] PPD, Richmond, VA USA. [Katori, Noriko] Japan MHLW NIHS, Tokyo, Japan. [Kaur, Surinder; Song, An] Genentech Inc, San Francisco, CA USA. [Kelley, Marian] MKelley Consulting LLC, W Chester, PA USA. [Knutsson, Magnus] Ferring Pharmaceut, Copenhagen, Denmark. [Lee, Jean; Ma, Mark; Shih, Judy; Thway, Theingi] Amgen Inc, Thousand Oaks, CA 91320 USA. [Lowes, Steve; Schultz, Gary] Quintiles Bioanalyt & ADME Labs, Ithaca, NY USA. [Ormsby, Eric; Simon, Craig] Hlth Canada TPD, Ottawa, ON, Canada. [Patel, Shefali] Janssen R&D, Spring House, PA USA. [Pucci, Vincenzo] Merck Res Labs, Boston, MA USA. [Ray, Chad] Pfizer, San Diego, CA USA. [Shoup, Ronald] AIT Biosci, Indianapolis, IN USA. [Neto, Joao Tavares] ANVISA, Brasilia, DF, Brazil. [Theobald, Valerie] Sanofi, Framingham, MA USA. [Wakelin-Smith, Jason; Whale, Emma] UK Med & Healthcare Prod Regulatory Agcy MHRA, Welwyn Garden City, Herts, England. [Wang, Laixin] Tandem Labs, Salt Lake City, UT USA. [Welink, Jan] Dutch Med Evaluat Board, Utrecht, Netherlands. [Woolf, Eric] Merck Res Labs, West Point, PA USA. [Xu, Raymond] AbbVie, N Chicago, IL USA. RP Garofolo, F (reprint author), Algorithme Pharma Inc, 575 Armand Frappier Blvd, Montreal, PQ H7V 4B3, Canada. EM fgarofolo@algopharm.com FU US FDA; Europe EMA; Health Canada; Netherlands MEB; Brazil ANVISA; Japan MHLW; UK MHRA FX The authors would like to acknowledge the US FDA, Europe EMA, Health Canada, The Netherlands MEB, Brazil ANVISA, Japan MHLW and UK MHRA for supporting this workshop. L Stevenson (Biogen Idec Inc.) for her major contribution in coordinating this White Paper for the biotherapeutics part. B DeSilva (Bristol-Myers Squibb), L Amaravadi (Biogen Idec Inc.), M Brudny-Kloeppel (Bayer Pharma AG), A Musuku, (Pharmascience) and F Garofolo (Algorithme Pharma Inc.) for chairing the workshop. L Stevenson (Biogen Idec Inc.) and M Rocci (ICON Development Solutions) for chairing the White Paper discussions. All the workshop attendees and members of the bioanalytical community who have sent comments and suggestions to complete this White Paper. I Dumont, S Martinez, C Dicaire, L Wright, L Mayrand-Provencher, M Losauro for collecting the workshop minutes and preparing the first draft of this White Paper. W Garofolo (Meeting Coordinator) for the logistic organization of the event. Future Science Group as a trusted partner. NR 27 TC 24 Z9 24 U1 0 U2 7 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 EI 1757-6199 J9 BIOANALYSIS JI Bioanalysis PD DEC PY 2013 VL 5 IS 23 BP 2903 EP 2918 DI 10.4155/bio.13.238 PG 16 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 272ZI UT WOS:000328501700012 PM 24107004 ER PT J AU Xu, ZZ Kalbfleisch, JD AF Xu, Zhenzhen Kalbfleisch, John D. TI Repeated Randomization and Matching in Multi-Arm Trials SO BIOMETRICS LA English DT Article DE BMW design; Clustered randomized trial; Experimental design; Optimal matching; Propensity score matching; Randomization tests; Repeated randomization ID RADIATION; EXPOSURE; DESIGN AB Cluster randomized trials with relatively few clusters have been widely used in recent years for evaluation of health-care strategies. The balance match weighted (BMW) design, introduced in Xu and Kalbfleisch (2010, Biometrics66, 813-823), applies the optimal full matching with constraints technique to a prospective randomized design with the aim of minimizing the mean squared error (MSE) of the treatment effect estimator. This is accomplished through consideration of M independent randomizations of the experimental units and then selecting the one which provides the most balance evaluated by matching on the estimated propensity scores. Often in practice, clinical trials may involve more than two treatment arms and multiple treatment options need to be evaluated. Therefore, we consider extensions of the BMW propensity score matching method to allow for studies with three or more arms. In this article, we propose three approaches to extend the BMW design to clinical trials with more than two arms and evaluate the property of the extended design in simulation studies. C1 [Xu, Zhenzhen] US FDA, CBER, Rockville, MD 20852 USA. [Kalbfleisch, John D.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. RP Xu, ZZ (reprint author), US FDA, CBER, Rockville, MD 20852 USA. EM zhenzhen.xu@fda.hhs.gov FU National Institute of Neurological Disorders and Stroke [RO1 NS050372]; University of Michigan Kidney Epidemiology and Cost Center FX The authors would like to thank Professors Ben Hansen, Douglas Schaubel and Thomas Braun for helpful discussions and Professor Phillip Scott for introducing them to the stroke studies that motivated this work. This work was supported in part by grant (RO1 NS050372) from the National Institute of Neurological Disorders and Stroke and by the University of Michigan Kidney Epidemiology and Cost Center. NR 22 TC 3 Z9 3 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD DEC PY 2013 VL 69 IS 4 BP 949 EP 959 DI 10.1111/biom.12077 PG 11 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 271WT UT WOS:000328423000015 PM 24134592 ER PT J AU Hodge, DR Prentice, KW Ramage, JG Prezioso, S Gauthier, C Swanson, T Hastings, R Basavanna, U Datta, S Sharma, SK Garber, EAE Staab, A Pettit, D Drumgoole, R Swaney, E Estacio, PL Elder, IA Kovacs, G Morse, BS Kellogg, RB Stanker, L Morse, SA Pillai, SP AF Hodge, David R. Prentice, Kristin Willner Ramage, Jason G. Prezioso, Samantha Gauthier, Cheryl Swanson, Tanya Hastings, Rebecca Basavanna, Uma Datta, Shomik Sharma, Shashi K. Garber, Eric A. E. Staab, Andrea Pettit, Denise Drumgoole, Rahsaan Swaney, Erin Estacio, Peter L. Elder, Ian A. Kovacs, Gerald Morse, Brenda S. Kellogg, Richard B. Stanker, Larry Morse, Stephen A. Pillai, Segaran P. TI COMPREHENSIVE LABORATORY EVALUATION OF A HIGHLY SPECIFIC LATERAL FLOW ASSAY FOR THE PRESUMPTIVE IDENTIFICATION OF RICIN IN SUSPICIOUS WHITE POWDERS AND ENVIRONMENTAL SAMPLES SO BIOSECURITY AND BIOTERRORISM-BIODEFENSE STRATEGY PRACTICE AND SCIENCE LA English DT Article ID RIBOSOME-INACTIVATING PROTEINS; COMMUNIS AGGLUTININ; CASTOR BEANS; TOXINS; GENE; SEQUENCE; AGENTS; CHAIN; ELECTROCHEMILUMINESCENCE; CYTOTOXICITY AB Ricin, a heterodimeric toxin that is present in the seeds of the Ricinus communis plant, is the biothreat agent most frequently encountered by law enforcement agencies in the United States. Even in untrained hands, the easily obtainable seeds can yield a highly toxic product that has been used in various types of threats, including white-powder letters. Although the vast majority of these threats are hoaxes, an impediment to accurate hazard assessments by first responders is the unreliability of rapid detection assays for ricin, such as lateral flow assays (LFAs). One of the complicating factors associated with LFAs is the incorporation of antibodies of poor specificity that cross-react with near-neighbors or with plant lectins that are capable of nonspecifically cross-linking the capture and detector antibodies. Because of the compelling and critical need to promote the interests of public safety and public health, the Department of Homeland Security conducted a comprehensive laboratory evaluation study of a commercial LFA for the rapid detection of ricin. This study was conducted using comprehensive inclusivity and exclusivity panels of ricin and near-neighbor plant materials, along with panels of lectins and white-powders, to determine the specificity, sensitivity, limits of detection, dynamic range, and repeatability of the assay for the specific intended use of evaluating suspicious white powders and environmental samples in the field. C1 [Hodge, David R.; Prentice, Kristin Willner] Booz Allen & Hamilton Inc, Mclean, VA 22102 USA. [Ramage, Jason G.; Pillai, Segaran P.] US Dept Homeland Secur, Sci & Technol Directorate, Chem & Biol Def Div, Washington, DC USA. [Prezioso, Samantha] Ctr Dis Control & Prevent, Natl Ctr Emerging & Zoonot Infect Dis, Div Foodborne Waterborne & Environm Dis, Atlanta, GA USA. [Gauthier, Cheryl; Swanson, Tanya; Hastings, Rebecca] Massachusetts Dept Publ Hlth, Bioterrorism Response Lab, State Lab Inst, Jamaica Plain, MA USA. [Basavanna, Uma] USAMRIID, Ft Detrick, MD USA. [Datta, Shomik; Sharma, Shashi K.; Garber, Eric A. E.] Food & Drug Adm, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD USA. [Pettit, Denise] NC Dept Hlth & Human Serv, North Carolina State Lab Publ Hlth, Raleigh, NC USA. [Drumgoole, Rahsaan; Swaney, Erin] Texas Dept State Hlth Serv, Emergency Preparedness Branch, Austin, TX USA. [Estacio, Peter L.] Lawrence Livermore Natl Lab, Environm Hlth & Qual Assurance, Livermore, CA USA. [Elder, Ian A.] US Dept Homeland Secur, Washington, DC USA. [Morse, Brenda S.; Kellogg, Richard B.] CDC, Natl Ctr Emerging & Zoonot Infect Dis, Div Preparedness & Emerging Infect, Lab Preparedness & Response Branch, Atlanta, GA 30333 USA. [Stanker, Larry] USDA ARS, Foodborne Toxin Detect & Prevent Res Unit, Albany, CA USA. [Morse, Stephen A.] CDC, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA. RP Hodge, DR (reprint author), Dept Homeland Secur, S&T BOD STOP 0201,245 Murray Lane, Washington, DC 20528 USA. EM David.Hodge@hq.dhs.gov NR 52 TC 13 Z9 13 U1 1 U2 12 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1538-7135 EI 1557-850X J9 BIOSECUR BIOTERROR JI Biosecur. Bioterror. PD DEC 1 PY 2013 VL 11 IS 4 BP 237 EP 250 DI 10.1089/bsp.2013.0053 PG 14 WC Public, Environmental & Occupational Health; International Relations SC Public, Environmental & Occupational Health; International Relations GA 276KT UT WOS:000328749900003 PM 24320219 ER PT J AU Strauss, DG Mewton, N Verrier, RL Nearing, BD Marchlinski, FE Killian, T Moxley, J Tereshchenko, LG Wu, KC Winslow, R Cox, C Spooner, PM Lima, JAC AF Strauss, David G. Mewton, Nathan Verrier, Richard L. Nearing, Bruce D. Marchlinski, Francis E. Killian, Tony Moxley, John Tereshchenko, Larisa G. Wu, Katherine C. Winslow, Raimond Cox, Christopher Spooner, Peter M. Lima, Joao A. C. TI Screening Entire Health System ECG Databases to Identify Patients at Increased Risk of Death SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE arrhythmias; cardiac; death; electrocardiography; fibrosis; mass screening ID SUDDEN CARDIAC DEATH; INFARCT TISSUE HETEROGENEITY; CORONARY-ARTERY-DISEASE; CHRONIC KIDNEY-DISEASE; MAGNETIC-RESONANCE; STRATIFICATION; ARRHYTHMIA; MORTALITY; CARDIOMYOPATHY; EPIDEMIOLOGY AB Background Current methods to identify patients at higher risk for sudden cardiac death, primarily left ventricular ejection fraction 35%, miss approximate to 80% of patients who die suddenly. We tested the hypothesis that patients with elevated QRS-scores (index of myocardial scar) and wide QRS-T angles (index abnormal depolarization-repolarization relationship) have high 1-year all-cause mortality and could be further risk stratified with clinical characteristics. Methods and Results We screened all 12-lead ECGs over 6 months at 2 large hospital systems and analyzed clinical characteristics and 1-year mortality. Patients with ECGs obtained in hospital areas with known high mortality rates were excluded. At the first hospital, QRS-score 5 and QRS-T angle 105 degrees identified 8.0% of patients and was associated with an odds ratio of 2.79 (95% confidence interval, 2.10-3.69) for 1-year mortality compared with patients below both ECG thresholds (13.9% versus 5.5% death rate). Left ventricular ejection fraction was >35% in 82% of the former group of patients, and addition of ECG measures to left ventricular ejection fraction increased the discrimination of death risk (P<0.0001). At the second hospital, the odds ratio was 2.42 (1.95-3.01) for 1-year mortality (8.8% versus 3.8%). Adjustment for patient characteristics eliminated interhospital differences. Multivariable adjusted odds ratio combining data from both hospitals was 1.53 (1.28-1.83). Increasing heart rate and chronic renal impairment further predicted mortality. Conclusions Screening hospital ECG databases with QRS-scoring and QRS-T angle analysis identifies patients with high 1-year all-cause mortality and predominantly preserved left ventricular ejection fraction. This approach may represent a widely available method to identify patients at increased risk of death. C1 [Strauss, David G.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Mewton, Nathan; Moxley, John; Tereshchenko, Larisa G.; Wu, Katherine C.; Spooner, Peter M.; Lima, Joao A. C.] Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Verrier, Richard L.; Nearing, Bruce D.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. [Marchlinski, Francis E.; Killian, Tony] Hosp Univ Penn, Div Cardiol, Dept Med, Philadelphia, PA 19104 USA. [Winslow, Raimond] Johns Hopkins Univ, Dept Biomed Engn, Inst Computat Med, Baltimore, MD USA. [Cox, Christopher] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Lima, JAC (reprint author), Johns Hopkins Univ Hosp, 600 N Wolfe St Blalock 524, Baltimore, MD 21287 USA. EM jlima@jhmi.edu OI Tereshchenko, Larisa/0000-0002-6976-1313 FU National Institutes of Health/National Heart, Lung, and Blood Institute [P20HL101397, R24HL085343]; Leducq Foundation; French Federation of Cardiology FX This research was supported in part by grants P20HL101397 and R24HL085343 from the National Institutes of Health/National Heart, Lung, and Blood Institute, the Leducq Foundation, and the French Federation of Cardiology. Johns Hopkins University has a research agreement with GE Healthcare, Inc, which provided technical support only to this project. NR 24 TC 10 Z9 10 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 EI 1941-3084 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD DEC PY 2013 VL 6 IS 6 BP 1156 EP 1162 DI 10.1161/CIRCEP.113.000411 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 273HN UT WOS:000328526000026 PM 24122522 ER PT J AU MacMahon, S Begley, TH Diachenko, GW AF MacMahon, Shaun Begley, Timothy H. Diachenko, Gregory W. TI Occurrence of 3-MCPD and glycidyl esters in edible oils in the United States SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT LA English DT Article DE 3-MCPD; glycidol; glycidyl esters; oils; processing contaminants ID FATTY-ACID ESTERS; ELAEIS-GUINEENSIS OIL; MASS-SPECTROMETRY; 3-CHLORO-1,2-PROPANEDIOL 3-MCPD; 3-MONOCHLOROPROPANE-1,2-DIOL; MONOCHLOROPROPANEDIOL; CONTAMINANTS; CELLS; RATS AB Fatty acid esters of 3-monochloropropanediol (3-MCPD) and glycidol are processing contaminants found in a wide range of edible oils. While both 3 MCPD and glycidol have toxicological properties that at present has concerns for food safety, the published occurrence data are limited. Occurrence information is presented for the concentrations of 3-MCPD and glycidyl esters in 116 retail and/or industrial edible oils and fats using LC-MS/MS analysis of intact esters. The concentrations for bound 3-MCPD ranged from below the limit of quantitation ( 0.05) in the prevalence was found between wet markets and supermarkets or between whole chickens and chopped chickens. The prevalence of ESBL-producing Salmonella differed significantly (P < 0.05) among different seasons, being higher in autumn than in spring and winter. Overall, ESBL-producing Salmonella varied significantly (P<0.05) among 12 detected Salmonella serotypes: Abony (1 [33.33%] of 3), Indiana (28 [28.57%] of 98), Edinburg (6 [24.00%] of 25), Shubra (2 [20.00%] of 10), Uppsala (1 [16.67%] of 6), Thompson (8 [14.81%] of 54), Haardt (1 [12.50%] of 8), Agona (3 [9.68%] of 31), Gueuletapee (1 [6.25%] of 16), Typhimurium (4 [5.56%] of 72), Heidelberg (1 [4.55%] of 22), and Enteritidis (4 [3.17%] of 126). This study revealed that ESBL-producing Salmonella do exist in retail chicken in the People's Republic of China and that the potential risk of their presence in foods needs further exploration. C1 [Wu, Haiyun; Xia, Xiaodong; Cui, Yue; Hu, Yuanyuan; Xi, Meili; Wang, Xin; Meng, Jianghong; Yang, Baowei] Northwest A&F Univ, Coll Food Sci, Yangling 712100, Peoples R China. [Shi, Xianming; Wang, Dapeng] Shanghai Jiao Tong Univ, Shanghai 200240, Peoples R China. [Meng, Jianghong] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. RP Yang, BW (reprint author), Northwest A&F Univ, Coll Food Sci, Yangling 712100, Peoples R China. EM ybwsheng@163.com FU "Fundamental Research Funds for the Central Universities" of Northwest A&F University, the People's Republic of China; "National High Technology Research and Development Program of China" (863 Program) [2012AA101601] FX This research was supported in part by the "Fundamental Research Funds for the Central Universities" of Northwest A&F University, the People's Republic of China, and the "National High Technology Research and Development Program of China" (863 Program) (no. 2012AA101601). NR 29 TC 9 Z9 9 U1 1 U2 22 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 DEC PY 2013 VL 76 IS 12 BP 2040 EP 2044 DI 10.4315/0362-028X.JFP-13-224 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 270EH UT WOS:000328301200007 PM 24290679 ER PT J AU Skates, SJ Gillette, MA LaBaer, J Carr, SA Anderson, L Liebler, DC Ransohoff, D Rifai, N Kondratovich, M Tezak, Z Mansfield, E Oberg, AL Wright, I Barnes, G Gail, M Mesri, M Kinsinger, CR Rodriguez, H Boja, ES AF Skates, Steven J. Gillette, Michael A. LaBaer, Joshua Carr, Steven A. Anderson, Leigh Liebler, Daniel C. Ransohoff, David Rifai, Nader Kondratovich, Marina Tezak, Zivana Mansfield, Elizabeth Oberg, Ann L. Wright, Ian Barnes, Grady Gail, Mitchell Mesri, Mehdi Kinsinger, Christopher R. Rodriguez, Henry Boja, Emily S. TI Statistical Design for Biospecimen Cohort Size in Proteomics-based Biomarker Discovery and Verification Studies SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE statistical experiment design; biomarker; proteomics; unbiasedness; power calculation ID MONITORING MASS-SPECTROMETRY; CARDIOVASCULAR-DISEASE; PROTEIN BIOMARKERS; MULTIPLEX ASSAYS; PIPELINE; PLASMA; ASSOCIATION; DIAGNOSTICS; VALIDATION; MARKERS AB Protein biomarkers are needed to deepen our understanding of cancer biology and to improve our ability to diagnose, monitor, and treat cancers. Important analytical and clinical hurdles must be overcome to allow the most promising protein biomarker candidates to advance into clinical validation studies. Although contemporary proteomics technologies support the measurement of large numbers of proteins in individual clinical specimens, sample throughput remains comparatively low. This problem is amplified in typical clinical proteomics research studies, which routinely suffer from a lack of proper experimental design, resulting in analysis of too few biospecimens to achieve adequate statistical power at each stage of a biomarker pipeline. To address this critical shortcoming, a joint workshop was held by the National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI), and American Association for Clinical Chemistry (AACC) with participation from the U.S. Food and Drug Administration (FDA). An important output from the workshop was a statistical framework for the design of biomarker discovery and verification studies. Herein, we describe the use of quantitative clinical judgments to set statistical criteria for clinical relevance and the development of an approach to calculate biospecimen sample size for proteomic studies in discovery and verification stages prior to clinical validation stage. This represents a first step toward building a consensus on quantitative criteria for statistical design of proteomics biomarker discovery and verification research. C1 [Skates, Steven J.] Massachusetts Gen Hosp, Ctr Canc, Ctr Biostat, Boston, MA 02114 USA. [Gillette, Michael A.; Carr, Steven A.] Broad Inst Massachusetts Inst Technol & Harvard, Prote Platform, Cambridge, MA 02142 USA. [LaBaer, Joshua] Arizona State Univ, Biodesign Inst, Tempe, AZ 85287 USA. [Anderson, Leigh] Plasma Proteome Inst, Washington, DC 20009 USA. [Anderson, Leigh; Wright, Ian] SISCAPA Technol Inc, Washington, DC 20009 USA. [Liebler, Daniel C.] Vanderbilt Univ, Sch Med, Jim Ayers Inst Precanc Detect & Diag, Nashville, TN 37232 USA. [Liebler, Daniel C.] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA. [Ransohoff, David] Univ N Carolina, Dept Med, Div Gastroenterol & Hepatol, Chapel Hill, NC 27514 USA. [Rifai, Nader] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Rifai, Nader] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Rifai, Nader] King Abdulaziz Univ, Jeddah 22254, Saudi Arabia. [Kondratovich, Marina; Tezak, Zivana; Mansfield, Elizabeth] US FDA, Off In Vitro Diagnost & Radiol Hlth, Ctr Devices & Radiol Hlth, Dept Hlth & Human Serv, Silver Spring, MD 20993 USA. [Oberg, Ann L.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN 55905 USA. [Barnes, Grady] Fujirebio Diagnost Inc, Malvern, PA 19355 USA. [Gail, Mitchell] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Mesri, Mehdi; Kinsinger, Christopher R.; Rodriguez, Henry; Boja, Emily S.] NCI, Off Canc Clin Prote Res, Ctr Strateg Sci Initiat, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Skates, SJ (reprint author), Massachusetts Gen Hosp, 50 Staniford St,Suite 560, Boston, MA 02114 USA. EM sskates@partners.org; bojae@mail.nih.gov OI Liebler, Daniel/0000-0002-7873-3031 FU National Cancer Institute of the National Institutes of Health through the Clinical Proteomic Tumor Analysis Consortium (CPTAC) [10XS136, U24CA160034]; Early Detection Research Network [U01CAI52990]; Mayo Clinic Specialized Program in Research Excellence [P50CA136393] FX Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grants and contracts through the Clinical Proteomic Tumor Analysis Consortium (CPTAC) program (10XS136 SJS, U24CA160034 SAC, MAG), the Early Detection Research Network (U01CAI52990 SJS), and Mayo Clinic Specialized Program in Research Excellence grant (P50CA136393 AO). NR 29 TC 32 Z9 32 U1 2 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 EI 1535-3907 J9 J PROTEOME RES JI J. Proteome Res. PD DEC PY 2013 VL 12 IS 12 BP 5383 EP 5394 DI 10.1021/pr400132j PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 269HD UT WOS:000328231300004 PM 24063748 ER PT J AU de las Heras, H Minniti, R Wilson, S Mitchell, C Skopec, M Brunner, CC Chakrabarti, K AF de las Heras, Hugo Minniti, Ronaldo Wilson, Sean Mitchell, Chad Skopec, Marlene Brunner, Claudia C. Chakrabarti, Kish TI Experimental estimates of peak skin dose and its relationship to the CT dose index using the CTDI head phantom SO RADIATION PROTECTION DOSIMETRY LA English DT Article ID PERFUSION COMPUTED-TOMOGRAPHY; RADIOCHROMIC FILM; CORONARY-ANGIOGRAPHY; ENERGY-DEPENDENCE; DOSIMETRY; SIMULATIONS; SCANNER; PATIENT AB A straightforward method is presented to estimate peak skin doses (PSDs) delivered by computed tomography (CT) scanners. The measured PSD values are related to the well-known volume CT dose index (CTDIvol), displayed on the console of CT scanners. PSD measurement estimates were obtained, in four CT units, by placing radiochromic film on the surface of a CTDI head phantom. Six different X-ray tube currents including the maximum allowed value were used to irradiate the phantom. PSD and CTDIvol were independently measured and later related to the CTDIvol value displayed on the console. A scanner-specific relationship was found between the measured PSD and the associated CTDIvol displayed on the console. The measured PSD values varied between 27 and 136 mGy among all scanners when the routine head scan parameters were used. The results of this work allow relating the widely used CTDIvol to an actual radiation dose delivered to the skin of a patient. C1 [de las Heras, Hugo; Brunner, Claudia C.; Chakrabarti, Kish] US FDA, Silver Spring, MD 20993 USA. [Minniti, Ronaldo] NIST, Gaithersburg, MD 20899 USA. [Wilson, Sean; Mitchell, Chad] Walter Reed Natl Mil Med Ctr, Bethesda, MD 20889 USA. [Skopec, Marlene] NIH, Bethesda, MD 20892 USA. RP de las Heras, H (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM hugo.heras@daad-alumni.de OI de las Heras, Hugo/0000-0003-3227-0032 FU Critical Path Project of FDA FX Kish Chakrabarti acknowledges funding from Critical Path Project of FDA, which enabled him to fund H.H. and C.B. for this work. NR 40 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 EI 1742-3406 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PD DEC PY 2013 VL 157 IS 4 BP 536 EP 542 DI 10.1093/rpd/nct171 PG 7 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 271FI UT WOS:000328376600008 PM 23864642 ER PT J AU Menis, M Sridhar, G Selvam, N Ovanesov, MV Divan, HA Liang, YD Scott, D Golding, B Forshee, R Ball, R Anderson, SA Izurieta, HS AF Menis, Mikhail Sridhar, Gayathri Selvam, Nandini Ovanesov, Mikhail V. Divan, Hozefa A. Liang, Yideng Scott, Dorothy Golding, Basil Forshee, Richard Ball, Robert Anderson, Steven A. Izurieta, Hector S. TI Hyperimmune globulins and same-day thrombotic adverse events as recorded in a large healthcare database during 2008-2011 SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID FACTOR-VIII GENE; SENSITIVE GEL-ELECTROPHORESIS; SEVERE HEMOPHILIA-A; LABORATORY NETWORK; MOLECULAR ANALYSIS; FACTOR-IX; MUTATION; POPULATION; INHIBITOR; MLPA AB Thrombotic events (TEs) are rare serious complications following administration of hyperimmune globulin (HIG) products. Our retrospective claims-based study assessed occurrence of same-day TEs following administration of HIGs during 2008-2011 and examined potential risk factors using HealthCore's Integrated Research Database (HIRDSM) and laboratory testing of products' procoagulant Factor XIa activity by U. S. Food and Drug Administration. Multivariable regression was used to estimate same-day TE risk for different products. Of 101,956 individuals exposed to 23 different HIG product groups, 86 (0.84 per 1,000 persons) had a TE diagnosis code (DC) recorded on the same day as HIG administration. Unadjusted same-day TE DC rates (per 1,000 persons) ranged from 0.4 to 148.9 for different products. GamaSTAN S/D IG > 10 cc had statistically significantly higher same-day TE DC risk compared to Tetanus IG (OR=57.57; 95% CI=19.72-168.10). Increased TE risk was also observed with older age (>= 45 years), prior thrombotic events, and hypercoagulable state(s). Laboratory investigation identified elevated Factor XIa activity for GamaSTAN S/D, HepaGam B, HyperHep B S/D, WinRho SDF, HyperRHO S/D full dose, and HyperTET S/D. Our study, for the first time, identified increase in the same-day TE DC risk with GamaSTAN S/D IG > 10 cc and suggests potentially elevated TE risk with other HIGs. Am. J. Hematol. 88: 1035-1040, 2013. (C) 2013 Wiley Periodicals, Inc. C1 [Menis, Mikhail; Ovanesov, Mikhail V.; Liang, Yideng; Scott, Dorothy; Golding, Basil; Forshee, Richard; Ball, Robert; Anderson, Steven A.; Izurieta, Hector S.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Sridhar, Gayathri; Selvam, Nandini; Divan, Hozefa A.] HealthCore Inc, Alexandria, VA 22311 USA. RP Sridhar, G (reprint author), HealthCore Inc, 2001 N Beauregard St,Suite 500, Alexandria, VA 22311 USA. EM gsridhar@healthcore.com FU U.S. Food and Drug Administration, Center for Biologics Evaluation and Research FX Contract grant sponsor: U.S. Food and Drug Administration, Center for Biologics Evaluation and Research. NR 31 TC 12 Z9 12 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD DEC PY 2013 VL 88 IS 12 BP 1035 EP 1040 DI 10.1002/ajh.23559 PG 6 WC Hematology SC Hematology GA 255FE UT WOS:000327224000131 PM 23907744 ER PT J AU Xiao, R Perveen, Z Rouse, RL Le Donne, V Paulsen, DB Ambalavanan, N Penn, AL AF Xiao, Rui Perveen, Zakia Rouse, Rodney L. Le Donne, Viviana Paulsen, Daniel B. Ambalavanan, Namasivayam Penn, Arthur L. TI In Utero Exposure to Second-Hand Smoke Aggravates the Response to Ovalbumin in Adult Mice SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE second-hand smoke; in utero exposure; mouse asthma model; inflammation; gene regulation ID CIGARETTE-SMOKE; ALLERGIC-ASTHMA; AIRWAY RESPONSIVENESS; PRENATAL EXPOSURE; MOUSE MODELS; INFLAMMATION; EXPRESSION; DISEASE; LUNG; PLETHYSMOGRAPHY AB Second-hand smoke (SHS) exposure in utero exacerbates adult responses to environmental irritants. We tested the hypothesis that effects of in utero SHS exposure on modulating physiological and transcriptome responses in BALB/c mouse lungs after ovalbumin (OVA) challenge extend well into adulthood, and that the responses show a sex bias. We exposed BALB/c mice in utero to SHS or filtered air (AIR), then sensitized and challenged all offspring with OVA from 19 to 23 weeks of age. At the end of the adult OVA challenge, we evaluated pulmonary function, examined histopathology, analyzed bronchoalveolar lavage fluid (BALF), and assessed gene expression changes in the lung samples. All groups exhibited lung inflammation and inflammatory cell infiltration. Pulmonary function testing (airway hyperresponsiveness [AHR], breathing frequency [f]) and BALF (cell differentials, Th1/Th2 cytokines) assessments showed significantly more pronounced lung responses in the SHS-OVA groups than in AIR-OVA groups (AHR, f; eosinophils, neutrophils; IFN-gamma, IL-1 beta, IL-4, IL-5, IL-10, IL-13, KC/CXCL1, TNF-alpha), with the majority of responses being more pronounced in males than in females. SHS exposure in utero also significantly altered lung gene expression profiles, primarily of genes associated with inflammatory responses and respiratory diseases, including lung cancer and lung fibrosis. Altered expression profiles of chemokines (Cxcl2, Cxcl5, Ccl8, Ccl24), cytokines (Il1b, Il6, Il13) and acute phase response genes (Saa1, Saa3) were confirmed by qRT-PCR. In conclusion, in utero exposure to SHS exacerbates adult lung responses to OVA challenge and promotes a pro-asthmatic milieu in adult lungs; further, males are generally more affected by SHS-OVA than are females. C1 [Xiao, Rui; Perveen, Zakia; Penn, Arthur L.] Louisiana State Univ, Sch Vet Med, Dept Comparat Biomed Sci, Baton Rouge, LA 70803 USA. [Le Donne, Viviana; Paulsen, Daniel B.] Louisiana State Univ, Sch Vet Med, Dept Pathobiol Sci, Baton Rouge, LA 70803 USA. [Rouse, Rodney L.] US FDA, Silver Spring, MD USA. [Ambalavanan, Namasivayam] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA. RP Penn, AL (reprint author), Room 2425 LSU SVM,Skip Bertman Dr, Baton Rouge, LA 70803 USA. EM apenn@vetmed.lsu.edu OI Xiao, Rui/0000-0001-8679-9551; Ambalavanan, Namasivayam/0000-0003-0731-9092 FU Louisiana Governor's Biotechnology Initiative; National Institutes of Health [HL092906] FX This research was supported by the Louisiana Governor's Biotechnology Initiative (A.L.P.) and National Institutes of Health grant HL092906 (N.A.). NR 37 TC 1 Z9 1 U1 0 U2 8 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 EI 1535-4989 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD DEC PY 2013 VL 49 IS 6 BP 1102 EP 1109 DI 10.1165/rcmb.2013-0164OC PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 269SI UT WOS:000328261800025 PM 23898987 ER PT J AU Ramachandran, P Lacher, DW Pfeiler, EA Elkins, CA AF Ramachandran, Padmini Lacher, David W. Pfeiler, Erika A. Elkins, Christopher A. TI Development of a Tiered Multilocus Sequence Typing Scheme for Members of the Lactobacillus acidophilus Complex SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID FRAGMENT LENGTH POLYMORPHISM; ET-AL 1980; PROBIOTIC LACTOBACILLI; SPECIES IDENTIFICATION; GENOME SEQUENCE; RAPD-PCR; SP-NOV; STRAIN; JOHNSONII; RECOMBINATION AB Members of the Lactobacillus acidophilus complex are associated with functional foods and dietary supplements because of purported health benefits they impart to the consumer. Many characteristics of these microorganisms are reported to be strain specific. Therefore, proper strain typing is essential for safety assessment and product labeling, and also for monitoring strain integrity for industrial production purposes. Fifty-two strains of the L. acidophilus complex (L. acidophilus, L. amylovorus, L. crispatus, L. gallinarum, L. gasseri, and L. johnsonii) were genotyped using two established methods and compared to a novel multilocus sequence typing (MLST) scheme. PCR restriction fragment length polymorphism (PCR-RFLP) analysis of the hsp60 gene with AluI and TaqI successfully clustered 51 of the 52 strains into the six species examined, but it lacked strain-level discrimination. Random amplified polymorphic DNA PCR (RAPD-PCR) targeting the M13 sequence resulted in highly discriminatory profiles but lacked reproducibility. In this study, an MLST scheme was developed using the conserved housekeeping genes fusA, gpmA, gyrA, gyrB, lepA, pyrG, and recA, which identified 40 sequence types that successfully clustered all of the strains into the six species. Analysis of the observed alleles suggests that nucleotide substitutions within five of the seven MLST loci have reached saturation, a finding that emphasizes the highly diverse nature of the L. acidophilus complex and our unconventional application of a typically intraspecies molecular typing tool. Our MLST results indicate that this method could be useful for characterization and strain discrimination of a multispecies complex, with the potential for taxonomic expansion to a broader collection of Lactobacillus species. C1 [Ramachandran, Padmini; Lacher, David W.; Pfeiler, Erika A.; Elkins, Christopher A.] US FDA, Div Mol Biol, CFSAN, Laurel, MD 20708 USA. RP Elkins, CA (reprint author), US FDA, Div Mol Biol, CFSAN, Laurel, MD 20708 USA. EM chris.elkins@fda.hhs.gov FU Food Safety and Applied Nutrition; FDA Commissioner's Fellowship Program; Oak Ridge Institute for Science and Education FX This study was funded by the Center for Food Safety and Applied Nutrition. Additional support for this project was provided by the FDA Commissioner's Fellowship Program and the Oak Ridge Institute for Science and Education. NR 33 TC 5 Z9 5 U1 0 U2 13 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 2013 VL 79 IS 23 BP 7220 EP 7228 DI 10.1128/AEM.02257-13 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 259RT UT WOS:000327544700012 PM 24038697 ER PT J AU Smith, SM Wang, AT Pereira, A Chang, RD McKeown, A Greene, K Rowbotham, MC Burke, LB Coplan, P Gilron, I Hertz, SH Katz, NP Lin, AH McDermott, MP Papadopoulos, EJ Rappaport, BA Sweeney, M Turk, DC Dworkin, RH AF Smith, Shannon M. Wang, Anthony T. Pereira, Anthony Chang, R. Daniel McKeown, Andrew Greene, Kaitlin Rowbotham, Michael C. Burke, Laurie B. Coplan, Paul Gilron, Ian Hertz, Sharon H. Katz, Nathaniel P. Lin, Allison H. McDermott, Michael P. Papadopoulos, Elektra J. Rappaport, Bob A. Sweeney, Michael Turk, Dennis C. Dworkin, Robert H. TI Discrepancies between registered and published primary outcome specifications in analgesic trials: ACTTION systematic review and recommendations SO PAIN LA English DT Review DE Analgesic medications; Clinical trials; Primary outcomes; Registry; Systematic review ID CLINICAL-TRIALS; REPORTING BIAS; DRUG TRIALS; EMPIRICAL-EVIDENCE; RANDOMIZED-TRIALS; CHRONIC PAIN; PUBLICATION; CLINICALTRIALS.GOV; REGISTRATION; PROTOCOLS AB The National Institutes of Health released the trial registry Clinical Trials. gov in 2000 to increase public reporting and clinical trial transparency. This systematic review examined whether registered primary outcome specifications (POS; ie, definitions, timing, and analytic plans) in analgesic treatment trials correspond with published POS. Trials with accompanying publications (n = 87) were selected from the Repository of Registered Analgesic Clinical Trials (RReACT) database of all postherpetic neuralgia, diabetic peripheral neuropathy, and fibromyalgia clinical trials registered at Clinical Trials. gov as of December 1, 2011. POS never matched precisely; discrepancies occurred in 79% of the registry-publication pairs (21% failed to register or publish primary outcomes [PO]). These percentages did not differ significantly between industry and non-industry-sponsored trials. Thirty percent of the trials contained unambiguous POS discrepancies (eg, omitting a registered PO from the publication, "demoting'' a registered PO to a published secondary outcome), with a statistically significantly higher percentage of non-industry-sponsored than industry-sponsored trials containing unambiguous POS discrepancies. POS discrepancies due to ambiguous reporting included vaguely worded PO registration; or failing to report the timing of PO assessment, statistical analysis used for the PO, or method to address missing PO data. At best, POS discrepancies may be attributable to insufficient registry requirements, carelessness (eg, failing to report PO assessment timing), or difficulty uploading registry information. At worst, discrepancies could indicate investigator impropriety (eg, registering imprecise PO ["pain''], then publishing whichever pain assessment produced statistically significant results). Improvements in PO registration, as well as journal policies requiring consistency between registered and published PO descriptions, are needed. (C) 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Smith, Shannon M.; Pereira, Anthony; Chang, R. Daniel; McKeown, Andrew] Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14627 USA. [Wang, Anthony T.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Greene, Kaitlin; Rowbotham, Michael C.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Burke, Laurie B.; Hertz, Sharon H.; Lin, Allison H.; Papadopoulos, Elektra J.; Rappaport, Bob A.] US FDA, Silver Spring, MD USA. [Coplan, Paul] Purdue Pharma LP, Stamford, CT USA. [Coplan, Paul] Univ Penn, Philadelphia, PA 19104 USA. [Gilron, Ian] Queens Univ, Dept Anesthesiol & Perioperat Med, Kingston, ON, Canada. [Gilron, Ian] Queens Univ, Dept Biomed & Mol Sci, Kingston, ON, Canada. [Katz, Nathaniel P.] Analges Solut, Natick, MA USA. [Katz, Nathaniel P.] Tufts Univ, Boston, MA 02111 USA. [McDermott, Michael P.] Univ Rochester, Sch Med & Dent, Dept Biostat & Computat Biol, Rochester, NY USA. [McDermott, Michael P.; Dworkin, Robert H.] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. [Sweeney, Michael] Depomed, Newark, CA USA. [Turk, Dennis C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Dworkin, Robert H.] Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY USA. [Dworkin, Robert H.] Univ Rochester, Sch Med & Dent, Ctr Human Expt Therapeut, Rochester, NY USA. RP Smith, SM (reprint author), Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14627 USA. EM shannon1_smith@urmc.rochester.edu OI Coplan, Paul/0000-0002-7078-7780 FU ACTTION; FDA; Astellas; Bristol-Myers Squibb; Collegium; Depomed; Eli Lilly; Horizon; Jazz; Johnson Johnson; Mallinckrodt; Pfizer; Purdue; Zalicus FX The authors report no conflict of interest. The views expressed in this article are those of the authors and no official endorsement by the U.S. Food and Drug Administration (FDA) or the pharmaceutical companies that provided unrestricted grants to support the activities of the ACTTION public-private partnership should be inferred. Financial support for this project was provided by the ACTTION public-private partnership, which has received research contracts, grants, or other revenue from the FDA, Astellas, Bristol-Myers Squibb, Collegium, Depomed, Eli Lilly, Horizon, Jazz, Johnson & Johnson, Mallinckrodt, Pfizer, Purdue, Zalicus, and other sources. NR 40 TC 11 Z9 11 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD DEC PY 2013 VL 154 IS 12 BP 2769 EP 2774 DI 10.1016/j.pain.2013.08.011 PG 6 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 260LK UT WOS:000327596200028 PM 23962590 ER PT J AU Rubin, C Myers, T Stokes, W Dunham, B Harris, S Lautner, B Annelli, J AF Rubin, Carol Myers, Tanya Stokes, William Dunham, Bernadette Harris, Stic Lautner, Beth Annelli, Joseph TI Review of Institute of Medicine and National Research Council Recommendations for One Health Initiative SO EMERGING INFECTIOUS DISEASES LA English DT Article AB Human health is inextricably linked to the health of animals and the viability of ecosystems; this is a concept commonly known as One Health. Over the last 2 decades, the Institute of Medicine (IOM) and the National Research Council (NRC) have published consensus reports and workshop summaries addressing a variety of threats to animal, human, and ecosystem health. We reviewed a selection of these publications and identified recommendations from NRC and IOM/NRC consensus reports and from opinions expressed in workshop summaries that are relevant to implementation of the One Health paradigm shift. We grouped these recommendations and opinions into thematic categories to determine if sufficient attention has been given to various aspects of One Health. We conclude that although One Health themes have been included throughout numerous IOM and NRC publications, identified gaps remain that may warrant targeted studies related to the One Health approach. C1 [Rubin, Carol; Myers, Tanya] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Stokes, William] NIEHS, Res Triangle Pk, NC 27709 USA. [Dunham, Bernadette] US FDA, Rockville, MD 20857 USA. [Harris, Stic] Dept Homeland Secur, Washington, DC USA. [Lautner, Beth] USDA, Des Moines, IA USA. [Annelli, Joseph] USDA, Riverdale, MD USA. RP Rubin, C (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd NE,Mailstop A30, Atlanta, GA 30333 USA. EM crubin@cdc.gov NR 29 TC 6 Z9 6 U1 1 U2 10 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD DEC PY 2013 VL 19 IS 12 BP 1913 EP 1917 DI 10.3201/eid1912.121659 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 263RV UT WOS:000327826600001 PM 24274461 ER PT J AU Galeotti, L van Dam, PM Loring, Z Chan, D Strauss, DG AF Galeotti, Loriano van Dam, Peter M. Loring, Zak Chan, Dulciana Strauss, David G. TI Evaluating strict and conventional left bundle branch block criteria using electrocardiographic simulations SO EUROPACE LA English DT Article DE Left bundle branch block; Cardiac resynchronization therapy; Electrocardiography; Simulations ID CARDIAC RESYNCHRONIZATION THERAPY; HEART RHYTHM SOCIETY; CONDUCTION DISTURBANCES; VENTRICULAR ACTIVATION; CLINICAL-CARDIOLOGY; OF-CARDIOLOGY; QRS DURATION; FAILURE; REPOLARIZATION; PREDICT AB Left bundle branch block (LBBB) is a critical predictor of patient benefit from cardiac resynchronization therapy (CRT), but recent studies suggest that one-third of patients diagnosed with LBBB by conventional electrocardiographic (ECG) criteria may have a false-positive diagnosis. In this study, we tested the hypothesis that recently proposed strict LBBB ECG criteria improve specificity in cases of left ventricular hypertrophy (LVH) /dilatation and incomplete LBBB. We developed five heart models based on a healthy male with increasing degrees of LV hypertrophy and/or dilation. With each model, we simulated six conduction types: normal conduction, four increments of delayed initiation of LV activation (incomplete LBBB), and complete LBBB. Simulated ECGs were evaluated for the presence of LBBB by conventional (LV conduction delay and QRSd 120 ms) and strict ECG criteria (LV conduction delay, QRSd 140 ms men or 130 ms women, and mid-QRS notching in at least two of the leads I, aVL, V1, V2, V5, and/or V6). Both conventional and strict LBBB criteria had 100 sensitivity. However, conventional criteria falsely diagnosed LBBB in cases with LVH LV dilated 10 mm, LVH or LV dilated 10 mm combined with LV initiation 6 ms after the right ventricle (RV), and with LV dilated 5 mm combined with LV initiation 12 ms after RV (48 specificity). Strict LBBB criteria resulted in no false positives (100 specificity). New strict LBBB criteria increase the specificity of complete LBBB diagnosis in the presence of LV hypertrophy/dilatation and incomplete LBBB, which is critical for selecting CRT patients. C1 [Galeotti, Loriano; Loring, Zak; Chan, Dulciana; Strauss, David G.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [van Dam, Peter M.] Radboud Univ Nijmegen, Med Ctr, NL-6525 EZ Nijmegen, Netherlands. [Loring, Zak] Duke Univ, Sch Med, Durham, NC 27710 USA. RP Strauss, DG (reprint author), 10903 New Hampshire Ave,WO62 1126, Silver Spring, MD 20993 USA. EM David.Strauss@fda.hhs.gov RI GALEOTTI, LORIANO/N-4240-2014 OI GALEOTTI, LORIANO/0000-0002-3200-9080 FU FDA Critical Path Initiative Grant; U.S. Department of Energy; U.S. Food and Drug Administration FX This work was supported by an FDA Critical Path Initiative Grant and 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 36 TC 13 Z9 15 U1 3 U2 10 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 DEC PY 2013 VL 15 IS 12 BP 1816 EP 1821 DI 10.1093/europace/eut132 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 262KK UT WOS:000327733700027 PM 23703366 ER PT J AU El Fiky, A Perreault, R McGinnis, GJ Rabin, RL AF El Fiky, Ashraf Perreault, Roger McGinnis, Gwendolyn J. Rabin, Ronald L. TI Attenuated expression of interferon-beta and interferon-lambda l by human alternatively activated macrophages SO HUMAN IMMUNOLOGY LA English DT Article ID DENGUE VIRUS-INFECTION; LEUKEMIA-CELL LINE; ASTHMA EXACERBATIONS; SIGNAL-TRANSDUCTION; IFN-ALPHA; DIFFERENTIATION; RHINOVIRUS; DEFICIENT; THP-1; IL-4R-ALPHA AB Macrophages can be polarized into classically (CAM) or alternatively (MM) activated macrophages with IFN-gamma or IL-4, respectively. CAM are associated with type 1 immune responses and are implicated in autoimmunity; AAM are associated with type 2 responses and are implicated in allergic diseases. An impediment in investigating macrophage biology using primary human monocyte derived macrophages is the wide inter-donor heterogeneity and the limited quantity of cells that survive in vitro polarization. To overcome this impediment, we established a protocol to generate CAM and AAM cultures derived from the THP-1 human promonocytic cell line. In this report, we demonstrate that THP-CAM and -AMM express gene and protein markers that define their primary human monocyte derived counterparts, such as IL-1 beta, CXCL10, and CXCL11 for CAM, and MRC1, IL-4 and CCL22 for AMM. In addition, we demonstrate that STAT6 is selectively activated in THP-AMM which, upon LPS stimulation, have an attenuated or delayed expression of IFN-beta, IFN-lambda 1, and IFN alpha/beta pathway genes compared to their CAM counterparts. Taken together, these findings may help further investigate human diseases associated with the alternatively activated macrophage phenotype using this reproducible in vitro macrophage model. (C) 2013 Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics. C1 [El Fiky, Ashraf; Perreault, Roger; McGinnis, Gwendolyn J.; Rabin, Ronald L.] US FDA, Ctr Biol Evaluat & Res, Lab Immunobiochem, Div Bacterial Parasit & Allergen Prod,Off Vaccine, Bethesda, MD 20892 USA. RP Rabin, RL (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Immunobiochem, Div Bacterial Parasit & Allergen Prod,Off Vaccine, Bldg 29,Room 203A,29 Lincoln Dr MSC 4555, Bethesda, MD 20892 USA. EM ronald.rabin@fda.hhs.gov FU Oak Ridge Institute for Science and Education (ORISE); FDA medical countermeasure initiative (McMi) FX This work was supported by funding from the Oak Ridge Institute for Science and Education (ORISE) and the FDA medical countermeasure initiative (McMi). We thank Jennifer Reed for critical review of this manuscript. NR 33 TC 5 Z9 5 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 EI 1879-1166 J9 HUM IMMUNOL JI Hum. Immunol. PD DEC PY 2013 VL 74 IS 12 BP 1524 EP 1530 DI 10.1016/j.humimm.2013.08.267 PG 7 WC Immunology SC Immunology GA 266HN UT WOS:000328014800005 PM 23993990 ER PT J AU Foley, SL Johnson, TJ Ricke, SC Nayak, R Danzeisen, J AF Foley, Steven L. Johnson, Timothy J. Ricke, Steven C. Nayak, Rajesh Danzeisen, Jessica TI Salmonella Pathogenicity and Host Adaptation in Chicken-Associated Serovars SO MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS LA English DT Review ID CHAIN FATTY-ACIDS; ENTERICA SEROTYPE TYPHIMURIUM; III SECRETION SYSTEM; INTESTINAL EPITHELIAL-CELLS; GENOMIC ISLAND 1; ANTIBIOTIC-RESISTANCE REGION; GRADIENT GEL-ELECTROPHORESIS; COMPLETE NUCLEOTIDE-SEQUENCE; FIBRONECTIN-BINDING PROTEIN; INTRACELLULAR GROWTH-RATE AB Enteric pathogens such as Salmonella enterica cause significant morbidity and mortality. S. enterica serovars are a diverse group of pathogens that have evolved to survive in a wide range of environments and across multiple hosts. S. enterica serovars such as S. Typhi, S. Dublin, and S. Gallinarum have a restricted host range, in which they are typically associated with one or a few host species, while S. Enteritidis and S. Typhimurium have broad host ranges. This review examines how S. enterica has evolved through adaptation to different host environments, especially as related to the chicken host, and continues to be an important human pathogen. Several factors impact host range, and these include the acquisition of genes via horizontal gene transfer with plasmids, transposons, and phages, which can potentially expand host range, and the loss of genes or their function, which would reduce the range of hosts that the organism can infect. S. Gallinarum, with a limited host range, has a large number of pseudogenes in its genome compared to broader-host-range serovars. S. enterica serovars such as S. Kentucky and S. Heidelberg also often have plasmids that may help them colonize poultry more efficiently. The ability to colonize different hosts also involves interactions with the host's immune system and commensal organisms that are present. Thus, the factors that impact the ability of Salmonella to colonize a particular host species, such as chickens, are complex and multifactorial, involving the host, the pathogen, and extrinsic pressures. It is the interplay of these factors which leads to the differences in host ranges that we observe today. C1 [Foley, Steven L.; Nayak, Rajesh] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Johnson, Timothy J.; Danzeisen, Jessica] Univ Minnesota, Dept Vet & Biomed Sci, St Paul, MN 55108 USA. [Ricke, Steven C.] Univ Arkansas, Ctr Food Safety & Dept Food Sci, Fayetteville, AR 72701 USA. RP Foley, SL (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR USA. EM steven.foley@fda.hhs.gov NR 403 TC 24 Z9 27 U1 7 U2 48 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1092-2172 EI 1098-5557 J9 MICROBIOL MOL BIOL R JI Microbiol. Mol. Biol. Rev. PD DEC PY 2013 VL 77 IS 4 BP 582 EP 607 DI 10.1128/MMBR.00015-13 PG 26 WC Microbiology SC Microbiology GA 265IR UT WOS:000327945100004 PM 24296573 ER PT J AU Kachko, A Loesgen, S Shahzad-ul-Hussan, S Tan, W Zubkova, I Takeda, K Wells, F Rubin, S Bewley, CA Major, ME AF Kachko, Alla Loesgen, Sandra Shahzad-ul-Hussan, Syed Tan, Wendy Zubkova, Iryna Takeda, Kazuyo Wells, Frances Rubin, Steven Bewley, Carole A. Major, Marian E. TI Inhibition of Hepatitis C Virus by the Cyanobacterial Protein Microcystis viridis Lectin: Mechanistic Differences between the High-Mannose Specific Lectins MVL, CV-N, and GNA SO MOLECULAR PHARMACEUTICS LA English DT Article DE hepatitis C; antiviral lectin; HCV entry inhibitor; cyanovirin-N (CV-N); HCVcc; biolayer interferometry ID HUMAN-IMMUNODEFICIENCY-VIRUS; CARBOHYDRATE-BINDING AGENTS; REVEALS EXTENDED MICROHETEROGENEITY; HIGH-AFFINITY BINDING; ANTI-HIV ACTIVITY; CYANOVIRIN-N; ENVELOPE GLYCOPROTEINS; GALANTHUS-NIVALIS; IMMUNE-RESPONSES; STRUCTURAL BASIS AB Plant or microbial lectins are known to exhibit potent antiviral activities against viruses with glycosylated surface proteins, yet the mechanism(s) by which these carbohydrate-binding proteins exert their antiviral activities is not fully understood. Hepatitis C virus (HCV) is known to possess glycosylated envelope proteins (gpE1E2) and to be potently inhibited by lectins. Here, we tested in detail the antiviral properties of the newly discovered Microcystis viridis lectin (MVL) along with cyanovirin-N (CV-N) and Galanthus nivalis agglutinin (GNA) against cell culture HCV, as well as their binding properties toward viral particles, target cells, and recombinant HCV glycoproteins. Using infectivity assays, CV-N, MVL, and GNA inhibited HCV with IC50 values of 0.6 nM, 30.4 nM, and 11.1 nM, respectively. Biolayer interferometry analysis demonstrated a higher affinity of GNA to immobilized recombinant HCV glycoproteins compared to CV-N and MVL. Complementary studies, including fluorescence-activated cell sorting (FACS) analysis, confocal microscopy, and pre- and post-virus binding assays, showed a complex mechanism of inhibition for CV-N and MVL that includes both viral and cell association, while GNA functions by binding directly to the viral particle. Combinations of GNA with CV-N or MVL in HCV infection studies revealed synergistic inhibitory effects, which can be explained by different glycan recognition profiles of the mainly high-mannoside specific lectins, and supports the hypothesis that these lectins inhibit through different and complex modes of action. Our findings provide important insights into the mechanisms by which lectins inhibit HCV infection. Overall, the data suggest MVL and CV-N have the potential for toxicity due to interactions with cellular proteins while GNA may be a better therapeutic agent due to specificity for the HCV gpE1E2. C1 [Kachko, Alla; Tan, Wendy; Zubkova, Iryna; Wells, Frances; Major, Marian E.] US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis Viruses, Div Viral Prod, Bethesda, MD 20892 USA. [Takeda, Kazuyo] US FDA, Ctr Biol Evaluat & Res, Microscopy & Imaging Core Facil, Bethesda, MD 20892 USA. [Rubin, Steven] US FDA, Ctr Biol Evaluat & Res, Lab Method Dev, Div Viral Prod, Bethesda, MD 20892 USA. [Loesgen, Sandra; Shahzad-ul-Hussan, Syed; Bewley, Carole A.] NIAID, Bioorgan Chem Lab, Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD 20892 USA. [Shahzad-ul-Hussan, Syed] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Major, ME (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis Viruses, Div Viral Prod, Bethesda, MD 20892 USA. EM Marian.Major@fda.hhs.gov FU Food and Drug Administration Intramural Research Program; Intramural Research Program, National Institutes of Health (NIDDK); Intramural AIDS Targeted Antiviral Program, Office of the Director (CAB) FX The authors thank Drs. Alain Debrabant and Rana Nagatkatti, Center for Biologics Evaluation and Research, FDA, for the usage of their Octet red 96 system. This work was supported by Food and Drug Administration Intramural Research Program, the Intramural Research Program, National Institutes of Health (NIDDK), and the Intramural AIDS Targeted Antiviral Program, Office of the Director (CAB). NR 57 TC 6 Z9 6 U1 0 U2 4 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 DEC PY 2013 VL 10 IS 12 BP 4590 EP 4602 DI 10.1021/mp400399b PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 263TS UT WOS:000327831500019 PM 24152340 ER PT J AU Chalbot, MCG da Costa, GG Kavouras, IG AF Chalbot, Marie-Cecile G. da Costa, Goncalo Gamboa Kavouras, Ilias G. TI NMR Analysis of the Water-Soluble Fraction of Airborne Pollen Particles SO APPLIED MAGNETIC RESONANCE LA English DT Article ID MAGNETIC-RESONANCE-SPECTROSCOPY; ORGANIC AEROSOL; MATTER; SIMILARITY; MIXTURES; H-1-NMR; IMAGES; FOREST; MODEL; GENE AB The analysis of ambient organic aerosols by nuclear magnetic resonance (NMR) spectroscopy is limited because of the large number of organic compounds present at low concentrations. Here, we demonstrate the integrative analysis of NMR spectra of airborne pollen particles using reference spectra, spectral similarity metrics, principal components analysis (PCA), and a chemical mass balance model to determine the predominant types of organic compounds. Strong associations among glucose, fucose, specific amino acids, and airborne pollen particles were observed by spectral similarity metrics and PCA. Carbohydrates accounted for about 51 % of the airborne pollen particles in the spectrum followed by amino acids (42 %) and other compounds (7 %). Overall, our investigations showed that analysis of NMR spectral data of mixtures of environmental organic compounds with pattern recognition methods may generate information on the chemical characteristics of the mixture. C1 [Chalbot, Marie-Cecile G.; Kavouras, Ilias G.] Univ Arkansas Med Sci, Dept Environm & Occupat Hlth, Little Rock, AR 72205 USA. [da Costa, Goncalo Gamboa] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Chalbot, MCG (reprint author), Univ Arkansas Med Sci, Dept Environm & Occupat Hlth, Little Rock, AR 72205 USA. EM mchalbot@uams.edu RI Kavouras, Ilias/H-7056-2012; OI Kavouras, Ilias/0000-0003-0436-3784; Kavouras, Ilias/0000-0003-0342-5306 NR 38 TC 5 Z9 5 U1 1 U2 15 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0937-9347 EI 1613-7507 J9 APPL MAGN RESON JI Appl. Magn. Reson. PD DEC PY 2013 VL 44 IS 12 BP 1347 EP 1358 DI 10.1007/s00723-013-0492-4 PG 12 WC Physics, Atomic, Molecular & Chemical; Spectroscopy SC Physics; Spectroscopy GA 257QX UT WOS:000327402000001 ER PT J AU Brinker, AD Lyndly, J Tonning, J Moeny, D Levine, JG Avigan, MI AF Brinker, Allen D. Lyndly, Jenna Tonning, Joseph Moeny, David Levine, Jonathan G. Avigan, Mark I. TI Profiling Cumulative Proportional Reporting Ratios of Drug-Induced Liver Injury in the FDA Adverse Event Reporting System (FAERS) Database SO DRUG SAFETY LA English DT Article ID SEVERE HEPATOTOXICITY; HEPATIC-FAILURE; SAFETY; TRANSPLANTATION; TELITHROMYCIN; CRITERIA AB Background Early prediction and accurate characterization of risk for serious liver injury associated with newly marketed drugs remains an important challenge for clinicians, the pharmaceutical industry, and regulators. To date, a biomarker that specifically indicates exposure to a drug as the etiologic cause of liver injury has not been identified. Objectives Using cumulative proportional reporting ratios (PRRs), we investigated 'real-time' profiles of a set of pharmaceuticals, over the first 3 years of US marketing, for the signaling of clinically serious drug-induced liver injury (DILI) in a large spontaneous-reporting database. Methods Using report counts of hepatic failure or clinically serious liver injury obtained from the FDA Adverse Events Reporting System (FAERS) database, PRRs of adverse drug event terms were calculated by division of counts of domestic reports of these events by counts of all serious adverse events for each of 13 selected drugs associated with a broad range of hepatotoxic risk (including three linked to only rare instances of clinically apparent liver injury) with reference to all other drugs in the database. Drug-specific cumulative PRRs were measured at successive intervals (calendar quarters) using cumulative tallies of FAERS reports to generate time-based profiles over the initial 3 years of US marketing. Results In the set of drugs analyzed, those with no known hepatotoxic risk demonstrated time-based cumulative PRR profiles that approximate the background rates of hepatic failure and serious liver injury reported in the entire FAERS database. In contrast, those that were removed from marketing or subjected to marketing restrictions due to their potential to cause liver injury were associated with profiles of rapidly rising cumulative PRRs that were greater than 5 within the first 10 million domestic prescriptions or the first four quarters of US marketing. The systematic tracking and identification of rising PRRs for DILI associated with newly marketed pharmaceutical and biological agents is a valuable tool for identification of safety signals within the FAERS database. Limitations Disproportionality profiling of spontaneous reports in FAERS (e.g., cumulative PRR measurements), which signals an association between a recently marketed drug and liver injury, is not a method to quantitatively measure drug-related risk. Regulatory actions in response to emerging drug safety concerns often depend on an accurate assessment of risks using multiple sources of data and the consideration of overall benefits and risks of the agent. Causality must be determined through analysis of individual cases to exclude other etiologies of liver injury. Conclusion The FAERS database can be used to advance empiric hepatotoxicity time-trending reporting levels for newly marketed agents in order to rapidly identify recently launched potential hepatotoxic agents and initiate further evaluation. C1 [Brinker, Allen D.; Lyndly, Jenna; Tonning, Joseph; Moeny, David; Levine, Jonathan G.; Avigan, Mark I.] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Brinker, AD (reprint author), US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM allen.brinker@fda.hhs.gov; jenna.lyndly@fda.hhs.gov; joseph.tonning@fda.hhs.gov; david.moeny@fda.hhs.gov; jonathan.levine@fda.hhs.gov; mark.avigan@fda.hhs.gov NR 45 TC 6 Z9 9 U1 0 U2 8 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 EI 1179-1942 J9 DRUG SAFETY JI Drug Saf. PD DEC PY 2013 VL 36 IS 12 BP 1169 EP 1178 DI 10.1007/s40264-013-0116-9 PG 10 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 257NF UT WOS:000327390800004 PM 24178291 ER PT J AU Han, J Gokulan, K Barnette, D Khare, S Rooney, AW Deck, J Nayak, R Stefanova, R Hart, ME Foley, SL AF Han, Jing Gokulan, Kuppan Barnette, Dustyn Khare, Sangeeta Rooney, Anthony W. Deck, Joanna Nayak, Rajesh Stefanova, Rossina Hart, Mark E. Foley, Steven L. TI Evaluation of Virulence and Antimicrobial Resistance in Salmonella enterica Serovar Enteritidis Isolates from Humans and Chicken- and Egg-Associated Sources SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID FIELD GEL-ELECTROPHORESIS; GENE PROFILES; TYPHIMURIUM; GENOME; FOOD; DIVERSITY; INFECTION; INTEGRONS; POULTRY; BRAZIL AB Salmonella enterica serovar Enteritidis is a leading cause of salmonellosis throughout the world and is most commonly associated with the consumption of contaminated poultry and egg products. Salmonella Enteritidis has enhanced ability to colonize and persist in extraintestinal sites within chickens. In this study, 54 Salmonella Enteritidis isolates from human patients (n=28), retail chicken (n=9), broiler farms (n=9), and egg production facilities (n=8) were characterized by antimicrobial susceptibility testing, plasmid analysis, genetic relatedness using XbaI and AvrII pulsed-field gel electrophoresis (PFGE), and the presence of putative virulence genes. Nine isolates were evaluated for their abilities to invade and survive in intestinal epithelial and macrophage cell lines. Overall, 56% (n=30) of isolates were resistant to at least one antimicrobial agent tested, yet no isolates showed resistance to more than three antimicrobials. All isolates carried a common approximate to 55-kb plasmid, with some strains containing additional plasmids ranging from 3 to 50kb. PFGE analysis revealed five XbaI and AvrII clusters. There were significant overlaps in the PFGE patterns of the isolates from human, chicken, and egg houses. All isolates tested PCR positive for iacP, purR, ttrB, spi4H, rmbA, sopE, invA, sopB, spvB, pagC, msgA, spaN, orgA, tolC, and sifA, and negative for iss, virB4, and sipB. Of the isolates selected for virulence testing, those containing the iron acquisition genes, iutA, sitA, and iucA, and approximate to 50-kb plasmids demonstrated among the highest levels of macrophage and epithelial cell invasion, which may indicate their importance in pathogenesis. C1 [Han, Jing; Gokulan, Kuppan; Barnette, Dustyn; Khare, Sangeeta; Rooney, Anthony W.; Deck, Joanna; Nayak, Rajesh; Hart, Mark E.; Foley, Steven L.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Barnette, Dustyn] Ouachita Baptist Univ, Dept Biol, Arkadelphia, AR USA. [Rooney, Anthony W.] Univ Minnesota, Dept Chem, Morris, MN 56267 USA. [Stefanova, Rossina] Arkansas Dept Hlth, Arkansas Publ Hlth Labs, Little Rock, AR 72205 USA. RP Foley, SL (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM steven.foley@fda.hhs.gov FU FDA Commissioner Fellowship Program; Oak Ridge Institute for Science and Education FX The authors would like to thank Drs. Carl Cerniglia, Huizhong Chen, and Mohamed Nawaz for their critical reviewing of the manuscript. Dr. Jing Han, Dustyn Barnette, and Anthony Rooney are supported through the Oak Ridge Institute for Science and Education. Dr. Kuppan Gokulan is supported by an FDA Commissioner Fellowship Program and by Oak Ridge Institute for Science and Education. NR 39 TC 10 Z9 11 U1 0 U2 16 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 DEC 1 PY 2013 VL 10 IS 12 BP 1008 EP 1015 DI 10.1089/fpd.2013.1518 PG 8 WC Food Science & Technology SC Food Science & Technology GA 255DR UT WOS:000327220100003 PM 24102082 ER PT J AU Fan, Y Ji, P Leonard-Segal, A Sahajwalla, CG AF Fan, Ying Ji, Ping Leonard-Segal, Andrea Sahajwalla, Chandrahas G. TI An Overview of the Pediatric Medications for the Symptomatic Treatment of Allergic Rhinitis, Cough, and Cold SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Review DE Allergic rhinitis; Cough and cold; Clinical pharmacology; Pediatrics; Pharmacokinetics; Clinical Pharmacokinetics; Population Pharmacokinetics; Pharmacodynamics ID AQUEOUS NASAL SPRAY; DOUBLE-BLIND; CHILDREN; SAFETY; IBUPROFEN; EFFICACY; ASTHMA; MANAGEMENT AB Upper respiratory infections and allergic rhinitis are common diseases in children. In recent years, U.S. Food and Drug Administration has been promoting pediatric drug development with marketing exclusivity incentives and requirements. The assessment of clinical pharmacology, efficacy, and safety data has facilitated pediatric drug development and provided appropriate labeling for pediatric use. Regulatory decision making involves multiple evaluation processes, including drug exposure comparison between adult and pediatric population, formulation bridging, dose selection, and evaluation of efficacy and safety in pediatric patients. This article reviews the pediatric drugs indicated for cough, cold, and allergic rhinitis, focusing on the utility of clinical pharmacology, safety, and efficacy data in determining the pediatric dosing regimen and the approaches taken for regulatory decision making. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:4213-4229, 2013 C1 [Fan, Ying; Ji, Ping; Sahajwalla, Chandrahas G.] US FDA, Off Clin Pharmacol, Div Clin Pharmacol 2, Silver Spring, MD 20993 USA. [Leonard-Segal, Andrea] US FDA, Off New Drugs, Div Nonprescript Clin Evaluat, Silver Spring, MD 20993 USA. RP Sahajwalla, CG (reprint author), US FDA, Off Clin Pharmacol, Div Clin Pharmacol 2, Silver Spring, MD 20993 USA. EM chandrahas.sahajwalla@fda.hhs.gov NR 77 TC 4 Z9 4 U1 0 U2 7 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 2013 VL 102 IS 12 BP 4213 EP 4229 DI 10.1002/jps.23720 PG 17 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 254UM UT WOS:000327193300001 PM 24185951 ER PT J AU Rahman, Z Siddiqui, A Khan, MA AF Rahman, Ziyaur Siddiqui, Akhtar Khan, Mansoor A. TI Characterization of a Nonribosomal Peptide Antibiotic Solid Dispersion Formulation by Process Analytical Technologies Sensors SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE solid dispersion; chemometrics; crystal defects; dissolution; multivariate analysis; powder X-ray diffration; fourier infrared spectroscopy; principle component analysis; partial least square analysis ID RAY-POWDER DIFFRACTION; NEAR-INFRARED SPECTROSCOPY; PHYSICAL STABILITY; DRUGS; QUANTITATION; VALIDATION; REGRESSION; RELEASE; SPECTRA; SYSTEMS AB The focus of present investigation was to characterize and evaluate the variability of solid dispersion (SD) of amorphous vancomycin (VCM), utilizing crystalline polyethylene glycol (PEG-6000) as a carrier and subsequently, determining their percentage composition by nondestructive method of process analytical technology (PAT) sensors. The SD were prepared by heat fusion method and characterized for physicochemical and spectral properties. Enhanced dissolution was shown by the SD formulations. Decreased crystallinity of PEG-6000 was observed indicating that the drug was present as solution and dispersed form within the polymer. The SD formulations were homogenous as shown by near infrared (NIR) chemical imaging data. Principal component analysis (PCA) and partial least square (PLS) method were applied to NIR and PXRD (powder X-ray diffraction) data to develop model for quantification of drug and carrier. PLS of both data showed correlation coefficient >0.9934 with good prediction capability as revealed by smaller value of root mean square and standard error. The model based on NIR and PXRD were two folds more accurate in estimating PEG-6000 than VCM. In conclusion, the drug dissolution from the SD increased by decreasing crystallinity of PEG-6000, and the chemometric models showed usefulness of PAT sensor in estimating percentage of both VCM and PEG-600 simultaneously. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:4337-4346, 2013 C1 [Rahman, Ziyaur; Siddiqui, Akhtar; Khan, Mansoor A.] US FDA, Ctr Drug Evaluat & Res, Div Prod Qual & Res, Rockville, MD 20857 USA. RP Khan, MA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Prod Qual & Res, Rockville, MD 20857 USA. EM Mansoor.Khan@fda.hhs.gov OI Rahman, Ziyaur/0000-0002-0402-825X NR 44 TC 5 Z9 5 U1 1 U2 12 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 2013 VL 102 IS 12 BP 4337 EP 4346 DI 10.1002/jps.23740 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 254UM UT WOS:000327193300013 PM 24114944 ER PT J AU Kakhi, M Chittenden, J AF Kakhi, Maziar Chittenden, Jason TI Modeling of Pharmacokinetic Systems Using Stochastic Deconvolution SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE absorption; mathematical models; in silico modeling; simulations; population pharmacokinetics; in vitro; in vivo correlation (IVIVC); stochastic deconvolution; nonlinear mixed effects (NLME) modeling ID IN-VITRO CORRELATION; DIFFERENTIAL-EQUATIONS; IMPLEMENTATION; LEVEL AB In environments where complete mechanistic knowledge of the system dynamics is not available, a synergy of first-principle concepts, stochastic methodsand statistical approaches can provide an efficient, accurate, and insightful strategy for model development. In this work, a system of ordinary differential equations describing system pharmacokinetics (PK) was coupled to a Wiener process for tracking the absorption rate coefficient, and was embedded in a nonlinear mixed effects population PK formalism. The procedure is referred to as stochastic deconvolution and itis proposed as a diagnostic tool to inform on a mapping function between the fraction of the drug absorbed and the fraction of the drug dissolved when applying one-stage methods to in vitro-in vivo correlation modeling. The goal of this work was to show that stochastic deconvolution can infer an a priori specified absorption profile given dense observational (simulated) data. The results demonstrate that the mathematical model is able to accurately reproduce the simulated data in scenarios where solution strategies for linear, time-invariant systems would assuredly fail. To this end, PK systems that are representative of Michaelis-Menten kinetics and enterohepatic circulation were investigated. Furthermore, the solution times are manageable using a modest computer hardware platform. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:4433-4443, 2013 C1 [Kakhi, Maziar] US FDA, Silver Spring, MD 20993 USA. [Chittenden, Jason] Pharsight Corp, Cary, NC 27518 USA. RP Kakhi, M (reprint author), US FDA, Silver Spring, MD 20993 USA. EM maziar.kakhi@fda.hhs.gov NR 21 TC 4 Z9 4 U1 1 U2 7 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 2013 VL 102 IS 12 BP 4433 EP 4443 DI 10.1002/jps.23752 PG 11 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 254UM UT WOS:000327193300023 PM 24174399 ER PT J AU Fardin-Kia, AR Delmonte, P Kramer, JKG Jahreis, G Kuhnt, K Santercole, V Rader, JI AF Fardin-Kia, Ali Reza Delmonte, Pierluigi Kramer, John K. G. Jahreis, Gerhard Kuhnt, Katrin Santercole, Viviana Rader, Jeanne I. TI Separation of the Fatty Acids in Menhaden Oil as Methyl Esters with a Highly Polar Ionic Liquid Gas Chromatographic Column and Identification by Time of Flight Mass spectrometry SO LIPIDS LA English DT Article DE Ionic liquid; SLB-IL111; GC; Gas chromatography; Menhaden oil; Marine oil; PUFA; GC-TOF/MS ID CP-SIL 88; FISH-OIL; CLA ISOMERS; DOCOSAHEXAENOIC ACID; WHALE OILS; MILK-FAT; GC; CHAIN; TRANS; CIS AB The fatty acids contained in marine oils or products are traditionally analyzed by gas chromatography using capillary columns coated with polyethylene glycol phases. Recent reports indicate that 100 % cyanopropyl siloxane phases should also be used when the analyzed samples contain trans fatty acids. We investigated the separation of the fatty acid methyl esters prepared from menhaden oil using the more polar SLB-IL111 (200 m x 0.25 mm) ionic liquid capillary column and the chromatographic conditions previously optimized for the separation of the complex mixture of fatty acid methyl esters prepared from milk fat. Identifications of fatty acids were achieved by applying Ag+-HPLC fractionation and GC-TOF/MS analysis in CI+ mode with isobutane as the ionization reagent. Calculation of equivalent chain lengths confirmed the assignment of double bond positions. This methodology allowed the identification of 125 fatty acids in menhaden oil, including isoprenoid and furanoid fatty acids, and the novel 7-methyl-6-hexadecenoic and 7-methyl-6-octadecenoic fatty acids. The chromatographic conditions applied in this study showed the potential of separating in a single 90-min analysis, among others, the short chain and trans fatty acids contained in dairy products, and the polyunsaturated fatty acids contained in marine products. C1 [Fardin-Kia, Ali Reza; Delmonte, Pierluigi; Rader, Jeanne I.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Kramer, John K. G.] Agr & Agri Food Canada, Guelph Food Res Ctr, Guelph, ON, Canada. [Jahreis, Gerhard; Kuhnt, Katrin] Univ Jena, Inst Nutr, Jena, Germany. [Santercole, Viviana] Univ Sassari, Fac Vet Med, I-07100 Sassari, Italy. RP Fardin-Kia, AR (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, HFS-717,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM alireza.fardinkia@fda.hhs.gov NR 46 TC 12 Z9 12 U1 2 U2 47 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0024-4201 EI 1558-9307 J9 LIPIDS JI Lipids PD DEC PY 2013 VL 48 IS 12 BP 1279 EP 1295 DI 10.1007/s11745-013-3830-2 PG 17 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 257TA UT WOS:000327408300010 PM 24043585 ER PT J AU Tembhare, PR Marti, G Wiestner, A Degheidy, H Farooqui, M Kreitman, RJ Jasper, GA Yuan, CM Liewehr, D Venzon, D Stetler-Stevenson, M AF Tembhare, Prashant R. Marti, Gerald Wiestner, Adrian Degheidy, Heba Farooqui, Mohammed Kreitman, Robert J. Jasper, Gregory A. Yuan, Constance M. Liewehr, David Venzon, David Stetler-Stevenson, Maryalice TI Quantification of Expression of Antigens Targeted by Antibody-Based Therapy in Chronic Lymphocytic Leukemia SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Chronic lymphocytic leukemia; Antibody therapy; Rituximab; Alemtuzumab; Quantitative flow cytometry ID QUANTITATIVE FLOW-CYTOMETRY; IMMUNOTOXIN RFB4(DSFV)-PE38 BL22; B-CELL LEUKEMIAS; PHASE-I TRIAL; CD20 EXPRESSION; LYMPHOPROLIFERATIVE DISORDERS; ALEMTUZUMAB CAMPATH-1H; RESIDUAL DISEASE; RITUXIMAB; FLUDARABINE AB Objectives: Anti-CD20 (rituximab), anti-CD52 (alemtuzumab), anti-CD22 (BL22, HA22), and anti-CD25 (Oncotac) are therapeutic options that are the mainstay or in preclinical development for the treatment of chronic lymphocytic leukemia (CLL). Studies suggest that levels of surface antigen expression may affect response to monoclonal antibody-based therapy. Methods: Using the flow cytometric Quantibrite method (BD Biosciences, San Jose, CA) to determine antibodies bound per cell, we quantified the levels of surface expression of CD20, CD22, CD25, and CD52 in CLL cells from 28 untreated patients. Results: The CLL cells in all cases expressed CD20, CD22, and CD52 but 4 (14%) cases were negative for CD25. Although the ranking of levels of expression from highest to lowest was CD52, CD20, CD22, and CD25, the level of antigen expression on any specific case could not be accurately predicted. Conclusions: Quantification of antigens might be useful in evaluating new antigens to target for therapy and may provide a systematic approach to selecting individualized therapy in CLL. (C) American Society for Clinical Pathology C1 [Tembhare, Prashant R.; Jasper, Gregory A.; Yuan, Constance M.; Stetler-Stevenson, Maryalice] NCI, Flow Cytometry Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Kreitman, Robert J.] NCI, Lab Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Liewehr, David; Venzon, David] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Marti, Gerald; Degheidy, Heba] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD USA. [Wiestner, Adrian; Farooqui, Mohammed] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Stetler-Stevenson, M (reprint author), NCI, Flow Cytometry Unit, Pathol Lab, Ctr Canc Res,NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM stetler@mail.nih.gov FU Intramural NIH HHS [Z01 BC011104-01] NR 31 TC 6 Z9 7 U1 0 U2 6 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD DEC PY 2013 VL 140 IS 6 BP 813 EP 818 DI 10.1309/AJCPYFQ4XMGJD6TI PG 6 WC Pathology SC Pathology GA 255ZX UT WOS:000327280400007 PM 24225748 ER PT J AU Simon, D Ware, T Marcotte, R Lund, BR Smith, DW Di Prima, M Rennaker, RL Voit, W AF Simon, Dustin Ware, Taylor Marcotte, Ryan Lund, Benjamin R. Smith, Dennis W., Jr. Di Prima, Matthew Rennaker, Robert L. Voit, Walter TI A comparison of polymer substrates for photolithographic processing of flexible bioelectronics SO BIOMEDICAL MICRODEVICES LA English DT Article DE Flexible electronics; Smart polymers; Neural interfaces ID SHAPE-MEMORY POLYMERS; BIOMEDICAL APPLICATIONS; MECHANICAL-PROPERTIES; NEURAL INTERFACES; IN-VIVO; ELECTRODES; POLYIMIDE; FILMS; DENSITY; SYSTEMS AB Flexible bioelectronics encompass a new generation of sensing devices, in which controlled interactions with tissue enhance understanding of biological processes in vivo. However, the fabrication of such thin film electronics with photolithographic processes remains a challenge for many biocompatible polymers. Recently, two shape memory polymer (SMP) systems, based on acrylate and thiol-ene/acrylate networks, were designed as substrates for softening neural interfaces with glass transitions above body temperature (37 A degrees C) such that the materials are stiff for insertion into soft tissue and soften through low moisture absorption in physiological conditions. These two substrates, acrylate and thiol-ene/acrylate SMPs, are compared to polyethylene naphthalate, polycarbonate, polyimide, and polydimethylsiloxane, which have been widely used in flexible electronics research and industry. These six substrates are compared via dynamic mechanical analysis (DMA), thermogravimetric analysis (TGA), and swelling studies. The integrity of gold and chromium/gold thin films on SMP substrates are evaluated with optical profilometry and electrical measurements as a function of processing temperature above, below and through the glass transition temperature. The effects of crosslink density, adhesion and cure stress are shown to play a critical role in the stability of these thin film materials, and a guide for the future design of responsive polymeric materials suitable for neural interfaces is proposed. Finally, neural interfaces fabricated on thiol-ene/acrylate substrates demonstrate long-term fidelity through both in vitro impedance spectroscopy and the recording of driven local field potentials for 8 weeks in the auditory cortex of laboratory rats. C1 [Simon, Dustin; Ware, Taylor; Di Prima, Matthew; Voit, Walter] Univ Texas Dallas, Dept Mat Sci & Engn, Richardson, TX 75080 USA. [Voit, Walter] Univ Texas Dallas, Dept Mech Engn, Richardson, TX 75080 USA. [Marcotte, Ryan] Univ Texas Dallas, Dept Elect Engn, Richardson, TX 75080 USA. [Lund, Benjamin R.; Smith, Dennis W., Jr.] Univ Texas Dallas, Dept Chem, Richardson, TX 75080 USA. [Rennaker, Robert L.] Univ Texas Dallas, Sch Brain & Behav Sci, Richardson, TX 75080 USA. [Di Prima, Matthew] Food & Drug Adm, CDRH OSEL DSFM, Silver Spring, MD 20993 USA. RP Voit, W (reprint author), Univ Texas Dallas, Dept Mat Sci & Engn, 800 West Campbell RD,Mailstop RL 10, Richardson, TX 75080 USA. EM walter.voit@utdallas.edu RI Ware, Taylor/A-7130-2017; OI Ware, Taylor/0000-0001-7996-7393; Di Prima, Matthew/0000-0003-1623-1324 FU National Institutes of Neurological Disorders and Stroke [5R01DC008982]; National Science Foundation [1147385]; State of Texas FX The authors would like to thank the FDA for the use of the Bruker Contour GT-K1 3D Optical Microscope. The opinions and/or conclusions expressed are solely those of the authors and in no way imply a policy or position of the Food and Drug Administration. This material is based partially based upon work supported from several sources: the National Institutes of Neurological Disorders and Stroke 5R01DC008982; the National Science Foundation Partnerships for Innovation and Graduate Research Fellowship under Grant No. 1147385; FUSION support from the State of Texas. NR 56 TC 12 Z9 12 U1 8 U2 78 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1387-2176 EI 1572-8781 J9 BIOMED MICRODEVICES JI Biomed. Microdevices PD DEC PY 2013 VL 15 IS 6 BP 925 EP 939 DI 10.1007/s10544-013-9782-8 PG 15 WC Engineering, Biomedical; Nanoscience & Nanotechnology SC Engineering; Science & Technology - Other Topics GA 253JM UT WOS:000327081100003 PM 23852172 ER PT J AU Lo Surdo, JL Millis, BA Bauer, SR AF Lo Surdo, Jessica L. Millis, Bryan A. Bauer, Steven R. TI Automated microscopy as a quantitative method to measure differences in adipogenic differentiation in preparations of human mesenchymal stromal cells SO CYTOTHERAPY LA English DT Article DE adipogenesis; bone marrow stromal cell; mesenchymal stromal cell; microscopy ID HUMAN BONE-MARROW; ADULT STEM-CELLS; IN-VITRO; OSTEOGENIC DIFFERENTIATION; ADIPOSE-TISSUE; PROGENITOR CELLS; EXPANSION; POPULATIONS; PRECURSORS; CULTURES AB Background aims. Multipotent stromal cells, also called mesenchymal stromal cells (MSCs), are potentially valuable as a cellular therapy because of their differentiation and immunosuppressive properties. As the result of extensive heterogeneity of MSCs, quantitative approaches to measure differentiation capacity between donors and passages on a per-cell basis are needed. Methods. Human bone marrow-derived MSCs were expanded to passages P3, P5 and P7 from eight different donors and were analyzed for colony-forming unit capacity (CPU), cell size, surface marker expression and forward/side-scatter analysis by flow cytometry. Adipogenic differentiation potential was quantified with the use of automated microscopy. Percentage of adipogenesis was determined by quantifying nuclei and Nile red positive adipocytes after automated image acquisition. Results. MSCs varied in expansion capacity and increased in average cell diameter with passage. CFU capacity decreased with passage and varied among cell lines within the same passage. The number of adipogenic precursors varied between cell lines, ranging from 0.5% to 13.6% differentiation at P3. Adipogenic capacity decreased significantly with increasing passage. MSC cell surface marker analysis revealed no changes caused by passaging or donor differences. Conclusions. We measured adipogenic differentiation on a per-cell basis with high precision and accuracy with the use of automated fluorescence microscopy. We correlated these findings with other quantitative bioassays to better understand the role of donor variability and passaging on CPU, cell size and adipogenic differentiation capacity in vitro. These quantitative approaches provide valuable tools to measure MSC quality and measure functional biological differences between donors and cell passages that are not revealed by conventional MSC cell surface marker analysis. C1 [Lo Surdo, Jessica L.; Bauer, Steven R.] Off Cellular Tissue & Gene Therapies, Div Cellular & Gene Therapies, FDA Ctr Biol Evaluat & Res, Bethesda, MD USA. [Millis, Bryan A.] NIDCD, NIH, Sect Struct Cell Biol, Bethesda, MD USA. RP Bauer, SR (reprint author), US FDA, Ctr Biol Evaluat & Res, NIH Bldg 29B HFM 740,Room 2NN10, Bethesda, MD 20892 USA. EM steven.bauer@fda.hhs.gov OI Bauer, Steven/0000-0003-2831-846X FU Jessica Lo Surdo's appointment to the Research Participation Program at the Center for Biologics Evaluation and Research; US Food and Drug Administration; Food and Drug Administration Modernizing Science grant program; Biomedical Advanced Research and Development Authority grant; Medical Countermeasures Initiative; Division of Cell and Gene Therapies FX The authors would like to acknowledge Eva Rudikoff for her assistance in growing the MSCs and Drs Brenton McCright, Deborah Hursh and Patrick Lynch for reviewing the manuscript. This project was supported in part by Jessica Lo Surdo's appointment to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through US Department of Education and US Food and Drug Administration. This work was also supported in part by the Food and Drug Administration Modernizing Science grant program, a Biomedical Advanced Research and Development Authority grant, a grant from the Medical Countermeasures Initiative and research funds from the Division of Cell and Gene Therapies. NR 62 TC 16 Z9 17 U1 0 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-3249 EI 1477-2566 J9 CYTOTHERAPY JI Cytotherapy PD DEC PY 2013 VL 15 IS 12 BP 1527 EP 1540 DI 10.1016/j.jcyt.2013.04.010 PG 14 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 254ME UT WOS:000327169000010 PM 23992827 ER PT J AU Kaur, P Chaurasia, CS Davit, BM Conner, DP AF Kaur, Paramjeet Chaurasia, Chandra S. Davit, Barbara M. Conner, Dale P. TI Bioequivalence Study Designs for Generic Solid Oral Anticancer Drug Products: Scientific and Regulatory Considerations SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE anticancer; bioequivalence; generics; guidances; pharmacokinetics ID 6-MERCAPTOPURINE; METHOTREXATE; BEXAROTENE AB The demonstration of bioequivalence (BE) between the test and reference products is an integral part of generic drug approval process. A sound BE study design is pivotal to the successful demonstration of BE of generic drugs to their corresponding reference listed drug product. Generally, BE of systemically acting oral dosage forms is demonstrated in a crossover, single-dose in vivo study in healthy subjects. The determination of BE of solid oral anticancer drug products is associated with its own unique challenges due to the serious safety risks involved. Unlike typical BE study in healthy subjects, the safety issues often necessitate conducting BE studies in cancer patients. Such BE studies of an anticancer drug should be conducted without disturbing the patients' therapeutic dosing regimen. Attributes such as drug permeability and solubility, pharmacokinetics, dosing regimen, and approved therapeutic indication(s) are considered in the BE study design of solid anticancer drug products. To streamline the drug approval process, the Division of Bioequivalence posts the Bioequivalence Recommendations for Specific Products guidances on the FDA public website. The objective of this article is to illustrate the scientific and regulatory considerations in the design of BE studies for generic solid oral anticancer drug products through examples. C1 [Kaur, Paramjeet; Chaurasia, Chandra S.; Davit, Barbara M.; Conner, Dale P.] US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Div Bioequivalence, Rockville, MD 20852 USA. RP Kaur, P (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Div Bioequivalence, Rockville, MD 20852 USA. EM paramjeet.kaur@fda.hhs.gov FU FDA Commissioner's Fellowship; ORISE Research Participation Program at the Center for Drug Evaluation and Research FX This project was supported in part by FDA Commissioner's Fellowship and also in part by an appointment to the ORISE Research Participation Program at the Center for Drug Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an agreement between the U. S. Department of Energy and CDER. The authors would also like to thank Hoainhon T. Nguyen, M. S. (Deputy Director, Division of Bioequivalence I) and Ethan Stier, Ph.D. (Deputy Director, Division of Bioequivalence II) for their suggestions during the development of Bioequivalence Recommendations for Specific Products guidances. Support provided by LCDR Duong Nhu, Pharm. D., Project Manager, DB II in preparation of this manuscript is also gratefully acknowledged. NR 28 TC 2 Z9 2 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4604 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD DEC PY 2013 VL 53 IS 12 BP 1252 EP 1260 DI 10.1002/jcph.163 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 252OB UT WOS:000327015000004 PM 23996908 ER PT J AU Park, M Sutherland, JB Kim, JN Rafii, F AF Park, Miseon Sutherland, John B. Kim, Jong Nam Rafii, Fatemeh TI Effect of Fluoroquinolone Resistance Selection on the Fitness of Three Strains of Clostridium perfringens SO MICROBIAL DRUG RESISTANCE LA English DT Article ID CAMPYLOBACTER-JEJUNI; COST; QUINOLONES; MUTATIONS; MUTANTS; DISEASE; GYRASE; TOXIN; COLI AB Selection of bacterial strains for resistance to antimicrobial agents may affect fitness; and fluoroquinolone resistance has been shown to affect fitness of aerobic and facultative bacteria. The impact on bacterial fitness of resistance selection to three fluoroquinolones was examined in three wild-type strains of Clostridium perfringens: ATCC 13124, ATCC 3626, and NCTR. Selection for resistance to norfloxacin, ciprofloxacin, and gatifloxacin affected the fitness of nine mutant strains differently. In a series of pure cultures grown in the absence of drugs, the growth of each of the mutants was comparable to that of the corresponding wild type. In competition experiments between mutants and isogenic wild types, however, some of the mutants were less fit. The fitness of ciprofloxacin-resistant mutants was comparable for all three strains, but two gatifloxacin-resistant mutants and one norfloxacin-resistant mutant were significantly less fit than the corresponding wild types. We conclude that both the genetic background of the strain and the fluoroquinolone which induced resistance affected the fitness of the resistant mutants. This is the first time that the effect on fitness of resistance to antimicrobial agents has been measured for C. perfringens. C1 [Park, Miseon; Sutherland, John B.; Kim, Jong Nam; Rafii, Fatemeh] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Rafii, F (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM fatemeh.rafii@fda.hhs.gov NR 30 TC 2 Z9 2 U1 2 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-6294 EI 1931-8448 J9 MICROB DRUG RESIST JI Microb. Drug Resist. PD DEC 1 PY 2013 VL 19 IS 6 BP 421 EP 427 DI 10.1089/mdr.2013.0056 PG 7 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 255PX UT WOS:000327253400001 PM 23789809 ER PT J AU Karnes, JH Gong, Y Pacanowski, MA McDonough, CW Arwood, MJ Langaee, TY Pepine, CJ Johnson, JA Cooper-DeHoff, RM AF Karnes, Jason H. Gong, Yan Pacanowski, Michael A. McDonough, Caitrin W. Arwood, Meghan J. Langaee, Taimour Y. Pepine, Carl J. Johnson, Julie A. Cooper-DeHoff, Rhonda M. TI Impact of TCF7L2 single nucleotide polymorphisms on hydrochlorothiazide-induced diabetes SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE diabetes mellitus; hydrochlorothiazide; pharmacogenetics; TCF7L2 ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; VERAPAMIL SR-TRANDOLAPRIL; JOINT NATIONAL COMMITTEE; BLOOD-PRESSURE CONTROL; CARDIOVASCULAR OUTCOMES; HYPERTENSIVE PATIENTS; SUSCEPTIBILITY LOCI; FASTING GLUCOSE; GENE-EXPRESSION AB ObjectiveThiazide diuretics have been associated with increased risk for new onset diabetes (NOD), but pharmacogenetic markers of thiazide-induced NOD are not well studied. Single nucleotide polymorphisms (SNPs) in the transcription factor 7-like 2 gene (TCF7L2) represent the strongest and most reproducible genetic associations with diabetes. We investigated the association of tag SNPs in TCF7L2 with thiazide-induced NOD.MethodsWe identified cases that developed NOD and age, sex, and race/ethnicity-matched controls from the INternational VErapamil SR-Trandolapril STudy (INVEST). INVEST compared cardiovascular outcomes between two antihypertensive treatment strategies in ethnically diverse patients with hypertension and coronary artery disease. We genotyped 101 TCF7L2 tag SNPs and used logistic regression to test for pharmacogenetic (SNPxhydrochlorothiazide treatment) interactions. Permuted interaction P values were corrected with the P-ACT test and adjusted for diabetes-related variables.ResultsIn INVEST whites, we observed three TCF7L2 SNPs with significant SNPxtreatment interactions for NOD. The strongest pharmacogenetic interaction was observed for rs7917983 [synergy index 3.37 (95% CI 1.72-6.59), P=5.0x10(-4), P-ACT=0.03], which was associated with increased NOD risk in hydrochlorothiazide-treated patients [odds ratio 1.53 (1.04-2.25), P=0.03] and decreased NOD risk in non hydrochlorothiazide-treated patients [odds ratio 0.48 (0.27-0.86), P=0.02]. The TCF7L2 SNP rs4506565, previously associated with diabetes, showed a similar, significant pharmacogenetic association.ConclusionOur results suggest that hydrochlorothiazide treatment is an environmental risk factor that increases diabetes risk beyond that attributed to TCF7L2 variation in white, hypertensive patients. Further study and replication of our results is needed to confirm pharmacogenetic influences of TCF7L2 SNPs on thiazide-induced NOD. C1 [Karnes, Jason H.] Vanderbilt Univ, Dept Med, Div Clin Pharmacol, Nashville, TN USA. [Karnes, Jason H.; Gong, Yan; McDonough, Caitrin W.; Arwood, Meghan J.; Langaee, Taimour Y.; Johnson, Julie A.; Cooper-DeHoff, Rhonda M.] Univ Florida, Dept Pharmacotherapy & Translat Res, Gainesville, FL 32610 USA. [Gong, Yan; Langaee, Taimour Y.; Johnson, Julie A.; Cooper-DeHoff, Rhonda M.] Univ Florida, Dept Pharmacotherapy & Translat Res, Ctr Pharmacogen, Gainesville, FL 32610 USA. [Pepine, Carl J.; Johnson, Julie A.; Cooper-DeHoff, Rhonda M.] Univ Florida, Div Cardiovasc Med, Dept Med, Gainesville, FL 32610 USA. [Pacanowski, Michael A.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. RP Cooper-DeHoff, RM (reprint author), Univ Florida, Dept Pharmacotherapy & Translat Res, POB 100486, Gainesville, FL 32610 USA. EM dehoff@cop.ufl.edu FU National Institutes of Health (Bethesda, Maryland, USA) [U01 GM074492]; Pharmacogenetics Research Network; National Institutes of Health [R01 HL74730, HL086558]; Abbott Laboratories; University of Florida Opportunity Fund; National Center for Research Resources [TL1RR029888]; National Institute of Child Health & Human Development [T32GM007569]; National Institute of General Medical Sciences FX This work is supported by a grant from the National Institutes of Health (Bethesda, Maryland, USA), grant U01 GM074492, funded as part of the Pharmacogenetics Research Network. Additional support for this work includes: National Institutes of Health grants R01 HL74730 and HL086558 (R.M.C.-D.); and grants from Abbott Laboratories and the University of Florida Opportunity Fund. The project described was supported by Award Number TL1RR029888 from the National Center for Research Resources (J.H.K.) and Award Number T32GM007569 from the National Institute of Child Health & Human Development and the National Institute of General Medical Sciences (J.H.K.). The authors thank Ben Burkley, Lynda Stauffer, and Cheryl Galloway for processing and genotyping samples and the patients who participated in INVEST-GENES. NR 50 TC 5 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1744-6872 EI 1744-6880 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD DEC PY 2013 VL 23 IS 12 BP 697 EP 705 DI 10.1097/FPC.0000000000000012 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 251YR UT WOS:000326971400006 PM 24128935 ER PT J AU Wysowski, DK Greene, P AF Wysowski, Diane K. Greene, Patty TI Trends in osteoporosis treatment with oral and intravenous bisphosphonates in the United States, 2002-2012 SO BONE LA English DT Article DE Bisphosphonates; Alendronate; Risedronate; Ibandronate; Osteoporosis ID FRACTURE INTERVENTION TRIAL; POSTMENOPAUSAL OSTEOPOROSIS; VERTEBRAL FRACTURES; RANDOMIZED-TRIAL; ZOLEDRONIC ACID; ALENDRONATE; BONE; WOMEN; RISK; OSTEONECROSIS AB Bisphosphonates have been widely prescribed to postmenopausal women for treatment and prevention of osteoporosis. Given a background of reports of recent safety problems, questions about optimal duration of use, and the patent expiration of Fosamax in February 2008, we accessed data from pharmaceutical marketing research databases to describe trends in dispensed prescriptions and sales of oral bisphosphonates, characteristics of patients and prescribers, and sales of intravenous bisphosphonates for osteoporosis treatment. An estimated 21.3 million prescriptions for oral bisphosphonates were dispensed in U.S. retail pharmacies in 2002 that increased 46% to a peak of 31.0 million in 2007 and 2008, and declined by 53% in a four year-period to 14.7 million in 2012. Sales data (number of packages sold in all settings of care) showed parallel trends (66% increase from 2002 through 2007 and 51% decrease from 2007 through 2012). Similarly, intravenous bisphosphonate sales for osteoporosis treatment grew 3.8-fold from 149.5 thousand packages in 2007 to 561.6 thousand in 2010, followed by a 22% decrease in 2012. Data from an ongoing monthly office-based survey indicated physicians mentioned oral bisphosphonates primarily in visits of older aged Caucasian women with lower body mass for osteoporosis. Frequencies of oral bisphosphonate mentions increased between 2002 and 2012 in visits of Asians and for osteopenia diagnoses. These data indicate a substantial decline in prescriptions and sales of oral (since 2007-2008) and intravenous (since 2010) bisphosphonates for osteoporosis treatment in the United States. Reasons for, and implications of, the decline should be considered for future research. Published by Elsevier Inc. C1 [Wysowski, Diane K.; Greene, Patty] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP Wysowski, DK (reprint author), US FDA, Div Epidemiol 1, Off Surveillance & Epidemiol, 10903 New Hampshire Ave,Bldg 22,Room 2406, Silver Spring, MD 20993 USA. EM diane.wysowski@fda.hhs.gov; patty.greene@fda.hhs.gov NR 28 TC 34 Z9 34 U1 0 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 EI 1873-2763 J9 BONE JI Bone PD DEC PY 2013 VL 57 IS 2 BP 423 EP 428 DI 10.1016/j.bone.2013.09.008 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 250JB UT WOS:000326848000014 PM 24063946 ER PT J AU Sheldon, LK Wise, B Carlson, JR Dowds, C Sarchet, V Sanchez, JA AF Sheldon, Lisa Kennedy Wise, Barbara Carlson, Julie R. Dowds, Cynthia Sarchet, Vanessa Sanchez, Jose Angel TI Developing a Longitudinal Cancer Nursing Education Program in Honduras SO JOURNAL OF CANCER EDUCATION LA English DT Article DE Nursing; Clinical oncology; Education; Developing countries ID HEALTH-CARE; PRIORITIES; COUNTRIES; MODEL AB The present paper is a longitudinal study which aims to develop and deliver cancer nursing education conferences in Honduras using volunteer nurse educators. This program intends to (1) perform site assessments of work environments and resources for cancer care in Honduras, (2) develop cancer nursing education programs, (3) survey conference participants continuing education needs, (4) deliver cancer nursing education conferences, and (5) share data with local and global partners for future cancer programs. The study draws on a longitudinal program development with site assessments, data collection, and educational conferences at two time points. Assessments and surveys were used for conference development and delivery by volunteer nurse educators. Site assessments and conferences were delivered twice. Data were collected regarding assessments and surveys to inform program development. Survey data revealed that < 4 % had formal training in cancer care and > 65 % had internet access. Participants desired more information about handling of chemotherapy, symptom management, and palliative care. Volunteer nurse educators perform site assessments and develop educational programming for cancer nurses. Local and global partners should explore internet-based programs between site visits to create sustainable education programs. C1 [Sheldon, Lisa Kennedy] Univ Massachusetts Boston, Boston, MA 02125 USA. [Wise, Barbara] US FDA, Silver Spring, MD USA. [Carlson, Julie R.] OSF St Anthony Med Ctr, Rockford, IL USA. [Dowds, Cynthia] Ashland Univ, Ashland, OH USA. [Sarchet, Vanessa] Amer Soc Clin Oncol, Washington, DC USA. [Sanchez, Jose Angel] Hosp Escuela Tegucigalpa, Tegucigalpa, Honduras. RP Sheldon, LK (reprint author), Univ Massachusetts Boston, 100 Morrissey Blvd, Boston, MA 02125 USA. EM lisa.kennedysheldon@umb.edu; bwisea@yahoo.com; Julie.R.Carlson@osfhealthcare.org; cdowds@ashland.edu; Vanessa.Sarchet@asco.org; jose.skiro@gmail.com OI Sheldon, Lisa Kennedy/0000-0002-5958-8529 NR 23 TC 3 Z9 3 U1 1 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-8195 EI 1543-0154 J9 J CANCER EDUC JI J. Cancer Educ. PD DEC PY 2013 VL 28 IS 4 BP 669 EP 675 DI 10.1007/s13187-013-0497-6 PG 7 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 242ZQ UT WOS:000326286200012 PM 23912757 ER PT J AU Gill, RB Bowman, JJ Krogmann, T Wollenberg, K Asher, DM Cohen, JI AF Gill, Rachel B. Bowman, J. Jason Krogmann, Tammy Wollenberg, Kurt Asher, David M. Cohen, Jeffrey I. TI Coding potential of UL/b ' from the initial source of rhesus cytomegalovirus Strain 68-1 SO VIROLOGY LA English DT Article DE Human cytomegalovirus; Rhesus cytomegalovirus; Cercopithecine herpesvirus: macacine herpesvirus 3; Cynomolgus macaque cytomegalovirus; UL/b ' ID ENDOTHELIAL-CELLS; ANTIBODY-RESPONSE; IN-VITRO; MACAQUES; COMPLEX; INFECTION; ENCODES; GENES; REPLICATION; CHEMOKINE AB Rhesus cytomegalovirus (RhCMV) 68-1 is the prototypic strain of RhCMV that has been used for pathogenesis and vaccine development. We determined the complete sequence of the RhCMV 68-1 UL/b' region directly from the original urine from which RhCMV 68-1 was isolated in 1968, and compared it to other RhCMVs. The laboratory passaged RhCMV 68-1 has inversions, deletions, and stop codons in UL/b' that are absent in the original isolate and other low passage RhCMV isolates. Fourteen of the 17 open reading frames (ORFs) in 68-1 UL/b' in the original isolate share >95% amino acid identity with low passage RhCMV. The original isolate retains 6 ORFs that encode alpha-chemokine-like proteins, including RhUL146 and RhUL146b that share only 92% and 81% amino acid identity, respectively, with a contemporary low passage RhCMV isolate. Identification of the original RhCMV 68-1 UL/b' sequence is important for using RhCMV 68-1 in pathogenesis and vaccine studies. (C) 2013 Elsevier Inc. All rights reserved. C1 [Gill, Rachel B.; Bowman, J. Jason; Krogmann, Tammy; Cohen, Jeffrey I.] NIH, Med Virol Sect, Infect Dis Lab, Bethesda, MD 20892 USA. [Wollenberg, Kurt] NIH, Bioinformat & Computat Biosci Branch, Bethesda, MD 20892 USA. [Asher, David M.] US FDA, Lab Bacterial & Transmissible Spongiform Encephal, Div Emerging & Transfus Transmitted Dis, Rockville, MD 20852 USA. RP Cohen, JI (reprint author), NIH, Infect Dis Lab, Bldg 50,Rm 6134,50 South Dr,MSC1807, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases FX This study was supported by the intramural research program of the National Institute of Allergy and Infectious Diseases. We thank Anita Mora and Heather Murphy of Rocky Mountain Laboratories (NIAID) for their assistance with artwork, Yanmei Wang for assistance with viral DNA quantification, and Peter Barry for advice with sequencing. NR 44 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD DEC PY 2013 VL 447 IS 1-2 BP 208 EP 212 DI 10.1016/j.virol.2013.08.026 PG 5 WC Virology SC Virology GA 246QF UT WOS:000326553500023 PM 24210116 ER PT J AU Rudneva, IA Timofeeva, TA Ignatieva, AV Shilov, AA Krylov, PS Ilyushina, NA Kaverin, NV AF Rudneva, Irina A. Timofeeva, Tatiana A. Ignatieva, Anna V. Shilov, Aleksandr A. Krylov, Petr S. Ilyushina, Natalia A. Kaverin, Nikolai V. TI Pleiotropic effects of hemagglutinin amino acid substitutions of H5 influenza escape mutants SO VIROLOGY LA English DT Article DE Influenza escape mutants; H5 hemagglutinin; Pleiotropic antibody-neutralizing mutations ID A VIRUS; ANTIGENIC SPECIFICITY; ADAPTATION; MOLECULE; EPITOPES; SITES AB In the present study we assessed pleiotropic characteristics of the antibody-selected mutations. We examined pH optimum of fusion, temperatures of HA heat inactivation, and in vitro and in vivo replication kinetics of the previously obtained influenza H5 escape mutants. Our results showed that HA1 N142K mutation significantly lowered the pH of fusion optimum. Mutations of the escape mutants located in the HA lateral loop significantly affected H5 HA thermostability (P < 0.05). HA changes at positions 131, 144, 145, and 156 and substitutions at positions 131, 142, 145, and 156 affected the replicative ability of H5 escape mutants in vitro and in vivo, respectively. Overall, a co-variation between antigenic specificity and different HA phenotypic properties has been demonstrated. We believe that the monitoring of pleiotropic effects of the HA mutations found in H5 escape mutants is essential for accurate prediction of mutants with pandemic potential. (C) 2013 Elsevier Inc. All rights reserved. C1 [Rudneva, Irina A.; Timofeeva, Tatiana A.; Ignatieva, Anna V.; Shilov, Aleksandr A.; Krylov, Petr S.; Kaverin, Nikolai V.] DI Ivanovskii Inst Virol, Moscow 123098, Russia. [Ilyushina, Natalia A.] FDA CDER, Bethesda, MD 20892 USA. RP Ilyushina, NA (reprint author), FDA CDER, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM Natalia.Ilyushina@fda.hhs.gov; nik.kaverin@gmail.com FU Russian Foundation for Basic Research (RFBR) [13-04-00257] FX We are especially grateful to Dr. Alexei G. Prilipov for helpful discussions and help with the experiments on HA thermostability. The work was supported by Grant #13-04-00257 of Russian Foundation for Basic Research (RFBR). NR 28 TC 3 Z9 3 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD DEC PY 2013 VL 447 IS 1-2 BP 233 EP 239 DI 10.1016/j.virol.2013.09.013 PG 7 WC Virology SC Virology GA 246QF UT WOS:000326553500026 PM 24210119 ER PT J AU Sanchez, MA Rabin, BA Gaglio, B Henton, M Elzarrad, MK Purcell, P Glasgow, RE AF Sanchez, Michael A. Rabin, Borsika A. Gaglio, Bridget Henton, Michelle Elzarrad, M. Khair Purcell, Peyton Glasgow, Russell E. TI A systematic review of eHealth cancer prevention and control interventions: new technology, same methods and designs? SO TRANSLATIONAL BEHAVIORAL MEDICINE LA English DT Review DE eHealth; Pragmatic trials; Systematic review; Design; PRECIS; External validity; RE-AIM framework AB There has been a recent surge of eHealth programs in cancer and other content areas, but few reviews have focused on the methodologies and designs employed in these studies. We conducted a systematic review of studies on eHealth interventions on cancer prevention and control published between 2001 and 2010 applying the Pragmatic Explanatory Continuum Indicator Summary (PRECIS) criteria and external validity components from the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework. We identified 113 studies that focused on cancer prevention and control of eHealth interventions. Most studies fell midway along the explanatory/pragmatic trial continuum, but few reported on various practical feasibility criteria for translation. Despite vast interest in cancer eHealth and the applied nature of this field, few studies considered key external validity issues. There is a need for use of alternative pragmatic study designs and transparent reporting of external validity components to produce more rapid and generalizable results. C1 [Sanchez, Michael A.; Elzarrad, M. Khair] NCI, Bethesda, MD 20892 USA. [Rabin, Borsika A.; Henton, Michelle] Kaiser Permanente Colorado, CRN Canc Commun Res Ctr, Denver, CO USA. [Gaglio, Bridget] Kaiser Permanente Midatlantic States, Midatlantic Permanente Res Inst, Rockville, MD USA. [Elzarrad, M. Khair] NCI, US FDA, Interagency Oncol Task Force IOTF Fellowship Canc, Bethesda, MD 20892 USA. [Purcell, Peyton] SAIC Frederick Inc, CMRP, Clin Res Directorate, Natl Lab Canc Res, Frederick, MD USA. RP Sanchez, MA (reprint author), NCI, Bethesda, MD 20892 USA. EM sanchezgarciama@mail.nih.gov FU National Cancer Institute Centers of Excellence in Cancer Communication Research [P20CA137219]; National Cancer Institute; National Institutes of Health [HHSN261200800001E] FX The preparation of this manuscript was partially funded through the National Cancer Institute Centers of Excellence in Cancer Communication Research (award number P20CA137219). This project has been funded, in whole or in part, with federal funds from the National Cancer Institute, the National Institutes of Health, under contract no. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does it mention of trade names, commercial products, or organizations implying endorsement by the US government. The opinions expressed are those of the authors and do not necessarily reflect those of the National Cancer Institute. NR 31 TC 8 Z9 8 U1 3 U2 6 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1869-6716 EI 1613-9860 J9 TRANSL BEHAV MED JI Transl. Behav. Med. PD DEC PY 2013 VL 3 IS 4 BP 392 EP 401 DI 10.1007/s13142-013-0224-1 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V39LR UT WOS:000209413000008 PM 24294327 ER PT J AU Erickson, MC Liao, J Payton, AS Webb, CC Ma, L Zhang, GD Flitcroft, I Doyle, MP Beuchat, LR AF Erickson, Marilyn C. Liao, Jean Payton, Alison S. Webb, Cathy C. Ma, Li Zhang, Guodong Flitcroft, Ian Doyle, Michael P. Beuchat, Larry R. TI Fate of Escherichia coli O157:H7 and Salmonella in soil and lettuce roots as affected by potential home gardening practices SO JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE LA English DT Article DE Salmonella; Escherichia coli O157:H7; internalization; lettuce; soil; water stress; compost amendment ID ENTERICA SEROVAR NEWPORT; MICROBIAL COMMUNITY; IRRIGATION WATER; ENDOPHYTIC COLONIZATION; ARABIDOPSIS-THALIANA; STRAIN SPECIFICITY; O157-H7; INTERNALIZATION; RHIZOSPHERE; SURVIVAL AB BACKGROUNDThe survival and distribution of enteric pathogens in soil and lettuce systems were investigated in response to several practices (soil amendment supplementation and reduced watering) that could be applied by home gardeners. RESULTSLeaf lettuce was grown in manure compost/top soil (0:5, 1:5 or 2:5 w/w) mixtures. Escherichia coliO157:H7 or Salmonella was applied at a low or high dose (10(3) or 10(6) colony-forming units (CFU) mL(-1)) to the soil of seedlings and mid-age plants. Supplementation of top soil with compost did not affect pathogen survival in the soil or on root surfaces, suggesting that nutrients were not a limiting factor. Salmonella populations on root surfaces were 0.7-0.8 log CFU g(-1) lower for mid-age plants compared with seedlings. E. coliO157:H7 populations on root surfaces were 0.8 log CFU g(-1) lower for mid-age plants receiving 40 mL of water compared with plants receiving 75 mL of water on alternate days. Preharvest internalization of E. coliO157:H7 and Salmonella into lettuce roots was not observed at any time. CONCLUSIONBased on the environmental conditions and high pathogen populations in soil used in this study, internalization of Salmonella or E. coliO157:H7 into lettuce roots did not occur under practices that could be encountered by inexperienced home gardeners. (c) 2013 Society of Chemical Industry C1 [Erickson, Marilyn C.; Liao, Jean; Payton, Alison S.; Webb, Cathy C.; Doyle, Michael P.; Beuchat, Larry R.] Univ Georgia, Ctr Food Safety, Griffin, GA 30223 USA. [Erickson, Marilyn C.; Liao, Jean; Payton, Alison S.; Webb, Cathy C.; Doyle, Michael P.; Beuchat, Larry R.] Univ Georgia, Dept Food Sci & Technol, Griffin, GA 30223 USA. [Ma, Li] Oklahoma State Univ, Natl Inst Microbial Forens & Food & Agr Biosecur, Stillwater, OK 74078 USA. [Zhang, Guodong] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Flitcroft, Ian] Univ Georgia, Dept Crop & Soil Sci, Griffin, GA 30223 USA. RP Erickson, MC (reprint author), Univ Georgia, Ctr Food Safety, 1109 Expt St, Griffin, GA 30223 USA. EM mericks@uga.edu FU Fresh Express, Inc.; USDA NIFSI [2007-51110-03812] FX Financial support for this study was provided in part by Fresh Express, Inc., by USDA NIFSI grant #2007-51110-03812 and by contributions to the University of Georgia's Center for Food Safety. Thanks are extended to Chris Smith, Lindsey Davey and Derrick Huckaby for their technical assistance. NR 58 TC 4 Z9 4 U1 2 U2 37 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-5142 EI 1097-0010 J9 J SCI FOOD AGR JI J. Sci. Food Agric. PD DEC PY 2013 VL 93 IS 15 BP 3841 EP 3849 DI 10.1002/jsfa.6321 PG 9 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 244PA UT WOS:000326400300025 PM 23893354 ER PT J AU Stine, CB Nochetto, C Gieseker, CM Evans, ER Hasbrouck, NR Mayer, TD Girard, L Reimschuessel, R AF Stine, C. B. Nochetto, C. Gieseker, C. M. Evans, E. R. Hasbrouck, N. R. Mayer, T. D. Girard, L. Reimschuessel, R. TI Depletion of melamine and cyanuric acid in kidney of catfish Ictalurus punctatus and trout Oncorhynchus mykiss SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID CRYSTAL-FORMATION; F344 RATS; EXPOSURE AB A risk assessment conducted in 2007 identified significant knowledge gaps about tissue residues of melamine and related triazine analogs such as cyanuric acid in animals that had eaten contaminated food. The USFDA subsequently designed studies to determine residue levels in muscle, serum, and kidneys of catfish and trout given a single gavage dose of 20mg/kg body weight (BW) of melamine, cyanuric acid, or 20mg/kg BW of both compounds simultaneously. Renal triazines were determined by LC-MS/MS at postdose days 1, 3, 7, 14, 28 (and day 42 for trout). When dosed individually, melamine and cyanuric acid kidney residues depleted much faster than those in fish given both compounds together. Combined dose residue depletion was punctuated by extreme outliers due to the formation of persistent renal melamine cyanurate crystals. C1 [Stine, C. B.; Nochetto, C.; Gieseker, C. M.; Evans, E. R.; Hasbrouck, N. R.; Mayer, T. D.; Girard, L.; Reimschuessel, R.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Stine, CB (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM Cynthia.Stine@fda.hhs.gov NR 16 TC 1 Z9 1 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0140-7783 EI 1365-2885 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD DEC PY 2013 VL 36 IS 6 BP 617 EP 620 DI 10.1111/jvp.12058 PG 4 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 246KE UT WOS:000326536000013 PM 23682764 ER PT J AU McCarthy, PC Saksena, R Peterson, DC Lee, CH An, YM Cipollo, JF Vann, WF AF McCarthy, Pumtiwitt C. Saksena, Rina Peterson, Dwight C. Lee, Che-Hung An, Yanming Cipollo, John F. Vann, Willie F. TI Chemoenzymatic synthesis of immunogenic meningococcal group C polysialic acid-tetanus Hc fragment glycoconjugates SO GLYCOCONJUGATE JOURNAL LA English DT Article DE Glycoconjugate vaccines; Neisseria meningitidis; Tetanus toxin C fragment; Chemoenzymatic synthesis; Click chemistry ID DIALKYL SQUARATE CHEMISTRY; HIGH-LEVEL EXPRESSION; ESCHERICHIA-COLI; NEISSERIA-MENINGITIDIS; CAMPYLOBACTER-JEJUNI; CAPSULAR POLYSACCHARIDE; CONJUGATE VACCINE; IMMUNE-RESPONSE; SIALIC ACIDS; O-ANTIGEN AB Vaccination with meningococcal glycoconjugate vaccines has decreased the incidence of invasive meningitis worldwide. These vaccines contain purified capsular polysaccharides attached to a carrier protein. Because of derivatization chemistries used in the process, conjugation of polysaccharide to protein often results in heterogeneous mixtures. Well-defined vaccines are needed to determine the relationship between vaccine structure and generated immune response. Here, we describe efforts to produce well-defined vaccine candidates by chemoenzymatic synthesis. Chemically synthesized lactosides were substrates for recombinant sialyltransferase enzymes from Camplyobacter jejuni and Neisseria meningitidis serogroup C. These resulting oligosialic acids have the same alpha(2-9) sialic acid repeat structure as Neisseria polysaccharide capsule with the addition of a conjugatable azide aglycon. The degree of polymerization (DP) of carbohydrate products was controlled by inclusion of the inhibitor CMP-9-deoxy-NeuNAc. Polymers with estimated DP < 47 (median DP 25) and DP < 100 (median DP 51) were produced. The receptor binding domain of the tetanus toxin protein (TetHc) was coupled as a carrier to the enzymatically synthesized oligosialic acids. Recombinant TetHc was derivatized with an alkyne squarate. Protein modification sites were determined by trypsin proteolysis followed by LC/MS-MSE analysis of peptides. Oligosialic acid azides were conjugated to modified TetHc via click chemistry. These chemoenzymatically prepared glycoconjugates were reactive in immunoassays with specific antibodies against either group C polysaccharide or TetHc. Sera of mice immunized with oligosialic acid-TetHc glycoconjugates contained much greater levels of polysaccharide-reactive IgG than the sera of control mice receiving unconjugated oligosialic acids. There was no apparent difference between glycoconjugates containing oligosaccharides of DP < 47 and DP < 100. These results suggest that chemoenzymatic synthesis may provide a viable method for making defined meningococcal vaccine candidates. C1 [McCarthy, Pumtiwitt C.; Saksena, Rina; Peterson, Dwight C.; Lee, Che-Hung; An, Yanming; Cipollo, John F.; Vann, Willie F.] US FDA, Lab Bacterial Polysaccharides, CBER, Bethesda, MD 20892 USA. RP Vann, WF (reprint author), US FDA, Lab Bacterial Polysaccharides, CBER, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM willie.vann@fda.hhs.gov FU Oak Ridge Institute for Science and Education; National Institutes of Health Pharmacology Research Associate Training (PRAT) Program FX P. C. M was supported by postdoctoral fellowships from the Oak Ridge Institute for Science and Education and the National Institutes of Health Pharmacology Research Associate Training (PRAT) Program. The authors acknowledge Justine Vionnet and Dr. Karen Muindi for technical assistance. The authors also acknowledge Drs. Daron Freedberg and Marcos Battistel for HSQC NMR spectra. NR 40 TC 8 Z9 8 U1 1 U2 23 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0282-0080 EI 1573-4986 J9 GLYCOCONJUGATE J JI Glycoconjugate J. PD DEC PY 2013 VL 30 IS 9 BP 857 EP 870 DI 10.1007/s10719-013-9490-x PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 241TB UT WOS:000326189600005 PM 23949787 ER PT J AU Zidan, AS Spinks, CB Habib, MJ Khan, MA AF Zidan, Ahmed S. Spinks, Crystal B. Habib, Muhammad J. Khan, Mansoor A. TI Formulation and transport properties of tenofovir loaded liposomes through Caco-2 cell model SO JOURNAL OF LIPOSOME RESEARCH LA English DT Article DE Caco-2; cytotoxicity; permeability; proliposomes; tenofovir ID DRUG-DELIVERY; CATIONIC LIPOSOMES; HIV-INFECTION; ABSORPTION; PERMEABILITY; DIFFUSION; PHARMACOKINETICS; DISOPROXIL; MONOLAYERS; CAVEOLAE AB The aim was to investigate the potential of proliposomes to improve the permeability of tenofovir, anti-HIV, for oral delivery. Tenofovir was incorporated into phosphatidylcholine proliposomes and their absorption was determined in Caco-2 cell cultures grown on Transwell inserts using aqueous drug solutions as reference. Five batches of proliposomes were prepared with different stearylamine levels and characterized in terms of vesicular morphology, drug encapsulation efficiency (EEF), drug leakage, vesicular sizing and surface charges. Cytotoxicity of the reconstituted liposomes was evaluated by the MTT assay. The obtained results showed that increasing the incorporated percentage of stearylamine led to an increase in drug encapsulation, a slower drug leakage and larger liposomes formed. Compared to the drug solutions at corresponding concentrations, the proposed formulations showed a positive relationship (R-2 = 0.9756) for the influence of increasing the stearylamine percentage on reduction of mitochondrial activity. Regarding the drug permeability, enhancements of apparent permeability by 16.5- and 5.2-folds were observed for proliposomes formulations with 5% and 15% stearylamine, respectively. A good correlation was observed between the Caco-2 and dialysis models that might indicate passive diffusion as well as paracellular transport as suggested mechanisms for drug absorption. Cationic proliposomes offered a potential formulation to improve the permeation of tenofovir. C1 [Zidan, Ahmed S.] King Abdulaziz Univ, Fac Pharm, Dept Pharmaceut & Ind Pharm, Jeddah 21413, Saudi Arabia. [Zidan, Ahmed S.] Zagazig Univ, Fac Pharm, Zagazig, Egypt. [Spinks, Crystal B.; Khan, Mansoor A.] US FDA, Div Prod Qual Res, Off Pharmaceut Sci, Rockville, MD 20857 USA. [Spinks, Crystal B.; Habib, Muhammad J.] Howard Univ, Dept Pharmaceut Sci, Sch Pharm, Washington, DC 20059 USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, Off Pharmaceut Sci, Rockville, MD 20857 USA. EM Manssor.khan@fda.hhs.gov RI Zidan, Ahmed/I-1147-2012 NR 49 TC 6 Z9 6 U1 0 U2 20 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0898-2104 EI 1532-2394 J9 J LIPOSOME RES JI J. Liposome Res. PD DEC PY 2013 VL 23 IS 4 BP 318 EP 326 DI 10.3109/08982104.2013.810645 PG 9 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 232VM UT WOS:000325522500007 PM 23915251 ER PT J AU Van Doren, JM Blodgett, RJ Pouillot, R Westerman, A Kleinmeier, D Ziobro, GC Ma, YQ Hammack, TS Gill, V Muckenfuss, MF Fabbri, L AF Van Doren, Jane M. Blodgett, Robert J. Pouillot, Regis Westerman, Ann Kleinmeier, Daria Ziobro, George C. Ma, Yinqing Hammack, Thomas S. Gill, Vikas Muckenfuss, Martin F. Fabbri, Linda TI Prevalence, level and distribution of Salmonella in shipments of imported capsicum and sesame seed spice offered for entry to the United States: Observations and modeling results SO FOOD MICROBIOLOGY LA English DT Article DE Salmonella contamination; Spice; Enumeration; Maximum likelihood estimation; Microbial contamination assessment ID MICROBIAL DISTRIBUTIONS; MICROBIOLOGICAL SAFETY; RISK-ASSESSMENT; ALFALFA SEEDS; NUT KERNELS; OUTBREAK; CONFIDENCE; PRODUCTS; GERMANY; IMPACT AB In response to increased concerns about spice safety, the United States Food and Drug Administration (FDA) initiated research to characterize the prevalence and levels of Salmonella in imported spices. 299 imported dried capsicum shipments and 233 imported sesame seed shipments offered for entry to the United States were sampled. Observed Salmonella shipment prevalence was 3.3% (1500 g examined; 95% CI 1.6-6.1%) for capsicum and 9.9% (1500 g; 95% Confidence Interval (CI) 6.3-14%) for sesame seed. Within shipment contamination was not inconsistent with a Poisson distribution. Shipment mean Salmonella level estimates among contaminated shipments ranged from 6 x 10(-4) to 0.09 (capsicum) or 6 x 10(-4) to 0.04 (sesame seed) MPN/g. A gamma-Poisson model provided the best fit to observed data for both imported shipments of capsicum and imported shipments of sesame seed sampled in this study among the six parametric models considered. Shipment mean levels of Salmonella vary widely between shipments; many contaminated shipments contain low levels of contamination. Examination of sampling plan efficacy for identifying contaminated spice shipments from these distributions indicates that sample size of spice examined is critical. Sampling protocols examining 25 g samples are predicted to be able to identify a small fraction of contaminated shipments of imported capsicum or sesame seeds. Published by Elsevier Ltd. C1 [Van Doren, Jane M.; Blodgett, Robert J.; Pouillot, Regis; Kleinmeier, Daria; Ziobro, George C.; Ma, Yinqing; Hammack, Thomas S.; Gill, Vikas] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Westerman, Ann; Fabbri, Linda] US FDA, Off Regulatory Affairs, Silver Spring, MD 20993 USA. [Muckenfuss, Martin F.] US FDA, Off Regulatory Affairs, Rockville, MD 20857 USA. RP Van Doren, JM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM jane.vandoren@fda.hhs.gov RI Pouillot, Regis/E-8103-2010 OI Pouillot, Regis/0000-0002-6107-5212 FU FDA; Center for Food Safety and Applied Nutrition FX The authors recognize and thank the hundreds of Office of Regulatory Affairs (ORA) field staff within FDA's district offices who participated in the sampling assignment associated with this study, including Consumer Safety Officers and Inspectors who collected spice shipment information, and laboratory scientists who analyzed the spice samples for presence of Salmonella, sero-typing and antibiotic resistance. We also thank and acknowledge FDA/CFSAN staff members who helped develop and implement the field assignment associated with this study. The results of this study will be incorporated into the risk profile on pathogens and filth being development by FDA and we thank the following risk profile team members who reviewed this manuscript: Drs. Mickey Parish and Obianugu Nsofor from FDA/CFSAN and Drs. Karen Neil and Laura Gieraltowski from CDC/OID. Additional scientists from CDC and FDA also provided helpful comments. This work was funded by the FDA. This work 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 U.S. Department of Energy and the FDA. NR 44 TC 7 Z9 7 U1 0 U2 29 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 2013 VL 36 IS 2 BP 149 EP 160 DI 10.1016/j.fm.2013.05.003 PG 12 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 226MF UT WOS:000325039700005 PM 24010593 ER PT J AU Hellberg, RS Martin, KG Keys, AL Haney, CJ Shen, YL Smiley, RD AF Hellberg, Rosalee S. Martin, Keely G. Keys, Ashley L. Haney, Christopher J. Shen, Yuelian Smiley, R. Derike TI 16S rRNA partial gene sequencing for the differentiation and molecular subtyping of Listeria species SO FOOD MICROBIOLOGY LA English DT Article DE Listeria; 16S rRNA gene; DNA sequencing; MicroSeq ID; Molecular subtyping ID INTRAGENOMIC HETEROGENEITY; CLINICAL MICROBIOLOGY; GENOME SEQUENCE; MULTIPLEX PCR; SP NOV.; IDENTIFICATION; MONOCYTOGENES; DIVERSITY; BACTERIA; STRAINS AB Use of 16S rRNA partial gene sequencing within the regulatory workflow could greatly reduce the time and labor needed for confirmation and subtyping of Listeria monocytogenes. The goal of this study was to build a 16S rRNA partial gene reference library for Listeria spp. and investigate the potential for 16S rRNA molecular subtyping. A total of 86 isolates of Listeria representing L innocua, L. seeligeri, L welshimeri, and L. monocytogenes were obtained for use in building the custom library. Seven non-Listeria species and three additional strains of Listeria were obtained for use in exclusivity and food spiking tests. Isolates were sequenced for the partial 16S rRNA gene using the MicroSeq ID 500 Bacterial Identification Kit (Applied Biosystems). High-quality sequences were obtained for 84 of the custom library isolates and 23 unique 16S sequence types were discovered for use in molecular subtyping. All of the exclusivity strains were negative for Listeria and the three Listeria strains used in food spiking were consistently recovered and correctly identified at the species level. The spiking results also allowed for differentiation beyond the species level, as 87% of replicates for one strain and 100% of replicates for the other two strains consistently matched the same 16S type. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Hellberg, Rosalee S.] Chapman Univ, Sch Earth & Environm Sci Food Sci & Nutr, Orange, CA 92866 USA. [Martin, Keely G.; Keys, Ashley L.; Haney, Christopher J.; Smiley, R. Derike] US FDA, Off Regulatory Affairs, Arkansas Reg Lab, Jefferson, AR 72079 USA. [Shen, Yuelian] US FDA, Off Regulatory Affairs, Off Reg Operat, Div Field Sci, Rockville, MD 20857 USA. RP Hellberg, RS (reprint author), Chapman Univ, Sch Earth & Environm Sci Food Sci & Nutr, 1 Univ Dr, Orange, CA 92866 USA. EM hellberg@chapman.edu NR 37 TC 10 Z9 11 U1 1 U2 31 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD DEC PY 2013 VL 36 IS 2 BP 231 EP 240 DI 10.1016/j.fm.2013.06.001 PG 10 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 226MF UT WOS:000325039700014 PM 24010602 ER PT J AU Buzatu, DA Cooper, WM Summage-West, C Sutherland, JB Williams, AJ Bass, DA Smith, LL Woodruff, RS Christman, JM Reid, S Tucker, RK Haney, CJ Ahmed, A Rafii, F Wilkes, JG AF Buzatu, Dan A. Cooper, Willie M. Summage-West, Christine Sutherland, John B. Williams, Anna J. Bass, Deborah A. Smith, Lisa L. Woodruff, Robert S. Christman, Jessica M. Reid, Steven Tucker, Randal K. Haney, Christopher J. Ahmed, Ashfaqe Rafii, Fatemeh Wilkes, Jon G. TI Photobleaching with phloxine B sensitizer to reduce food matrix interference for detection of Escherichia coli serotype O157:H7 in fresh spinach by flow cytometry SO FOOD MICROBIOLOGY LA English DT Article DE Flow cytometry; RAPID-B; Food matrix interference; Photobleaching; Same day analysis; Escherichia coli O157:H7 ID SAMPLE PREPARATION; APPLE JUICE; O157-H7; OUTBREAK; O157/H7 AB A flow cytometric method (RAPlD-B (TM)) with detection sensitivity of one viable cell of Escherichia coli serotype O157:H7 in fresh spinach (Spinacia oleracea) was developed and evaluated. The major impediment to achieving this performance was mistaking autofluorescing spinach particles for tagged target cells. Following a 5 h non-selective enrichment, artificially inoculated samples were photobleached, using phloxine B as a photosensitizer. Samples were centrifuged at high speed to concentrate target cells, then gradient centrifuged to separate them from matrix debris. In external laboratory experiments, RAPID-B and the reference method both correctly detected E. coli 0157:H7 at inoculations of ca. 15 cells. In a follow-up study, after 4 cell inoculations of positives and 6 h enrichment, RAPID-B correctly identified 92% of 25 samples. The RAPID-B method limit of detection (LOD) was one cell in 25 g. It proved superior to the reference method (which incorporated real time-PCR, selective enrichment, and culture plating elements) in accuracy and speed. Published by Elsevier Ltd. C1 [Buzatu, Dan A.; Cooper, Willie M.; Summage-West, Christine; Sutherland, John B.; Williams, Anna J.; Tucker, Randal K.; Rafii, Fatemeh; Wilkes, Jon G.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Bass, Deborah A.; Smith, Lisa L.; Woodruff, Robert S.; Christman, Jessica M.; Reid, Steven; Ahmed, Ashfaqe] US FDA, Arkansas Reg Lab, Jefferson, AR 72079 USA. [Haney, Christopher J.] US FDA, Ctr Tobacco Prod, Rockville, MD 20850 USA. RP Wilkes, JG (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM dan.buzatu@fda.hhs.gov; willie.cooper@fda.hhs.gov; christine.summage-west@fda.hhs.gov; john.sutherland@fda.hhs.gov; anna.williams@fda.hhs.gov; deborah.bass@fda.hhs.gov; lisal.smith@fda.hhs.gov; robert.woodruff@fda.hhs.gov; jessica.christman@fda.hhs.gov; steven.reid@fda.hhs.gov; viceroy@arkansas.net; christopher.haney@fda.hhs.gov; fatemeh.rafii@fda.hhs.gov; jon.wilkes@fda.hhs.gov NR 29 TC 7 Z9 7 U1 4 U2 39 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 2013 VL 36 IS 2 BP 416 EP 425 DI 10.1016/j.fm.2013.07.007 PG 10 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 226MF UT WOS:000325039700036 PM 24010624 ER PT J AU Van Doren, JM Neil, KP Parish, M Gieraltowski, L Gould, LH Gombas, KL AF Van Doren, Jane M. Neil, Karen P. Parish, Mickey Gieraltowski, Laura Gould, L. Hannah Gombas, Kathy L. TI Foodborne illness outbreaks from microbial contaminants in spices, 1973-2010 SO FOOD MICROBIOLOGY LA English DT Review DE Foodborne illness; Spice; Salmonella; Food safety; Microbial contaminants ID UNITED-STATES; MICROBIOLOGICAL QUALITY; HUMAN SALMONELLOSIS; BLACK PEPPER; FOOD; INFECTIONS; PATHOGENS; PREVALENCE; RESISTANCE; PRODUCTS AB This review identified fourteen reported illness outbreaks attributed to consumption of pathogen-contaminated spice during the period 1973-2010. Countries reporting outbreaks included Canada, Denmark, England and Wales, France, Germany, New Zealand, Norway, Serbia, and the United States. Together, these outbreaks resulted in 1946 reported human illnesses, 128 hospitalizations and two deaths. Infants/children were the primary population segments impacted by 36% (5/14) of spice-attributed outbreaks. Four outbreaks were associated with multiple organisms. Salmonella enterica subspecies enterica was identified as the causative agent in 71% (10/14) of outbreaks, accounting for 87% of reported illnesses. Bacillus spp. was identified as the causative agent in 29% (4/10) of outbreaks, accounting for 13% of illnesses. 71% (10/14) of outbreaks were associated with spices classified as fruits or seeds of the source plant. Consumption of ready-to-eat foods prepared with spices applied after the final food manufacturing pathogen reduction step accounted for 70% of illnesses. Pathogen growth in spiced food is suspected to have played a role in some outbreaks, but it was not likely a contributing factor in three of the larger Salmonella outbreaks, which involved low-moisture foods. Root causes of spice contamination included contributions from both early and late stages of the farm-to-table continuum. Published by Elsevier Ltd. C1 [Van Doren, Jane M.; Parish, Mickey; Gombas, Kathy L.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Neil, Karen P.; Gieraltowski, Laura; Gould, L. Hannah] Ctr Dis Control & Prevent, Natl Ctr Emerging & Zoonot Infect Dis, Div Foodborne Waterborne & Environm Dis, Atlanta, GA 30333 USA. RP Van Doren, JM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM jane.vandoren@fda.hhs.gov FU United States FDA; CDC FX The authors thank the many federal, state and international scientists who discussed the outbreak investigations with the authors and in some cases, provided additional information about the outbreak investigations that were incorporated into this manuscript, especially C. L Little (Health Protection Agency, United Kingdom.), G. Delmas (Institut de Veille Sanitaire, France), J. Higa (California Department of Public Health), R. Ireland and D. Quilliam (Rhode Island Department of Public Health), and M. Allard, T. DuVernoy, E. Pomeroy, S. Gordon, and E. Strain (FDA). We also thank S. Mettee for her assistance in reviewing CDC's Foodborne Disease Outbreak and Surveillance System, and I. Williams (CDC), for his feedback on this manuscript throughout its development. The results of this study will be incorporated into the risk profile on pathogens and filth in spices being developed by FDA and we thank the following risk profile team members who reviewed and commented on this manuscript: V. Gill, D. Kleinmeier, M. Muckenfuss, O. Nsofor, A. Westerman, and G. C. Ziobro (FDA). Additional scientists from CDC and FDA also provided helpful comments. This work was funded by the United States FDA and CDC. NR 71 TC 16 Z9 17 U1 1 U2 88 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD DEC PY 2013 VL 36 IS 2 BP 456 EP 464 DI 10.1016/j.fm.2013.04.014 PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 226MF UT WOS:000325039700041 PM 24010629 ER PT J AU Micallef, SA Goldstein, RER George, A Ewing, L Tall, B Boyer, MS Joseph, SW Sapkota, AR AF Micallef, Shirley A. Goldstein, Rachel E. Rosenberg George, Ashish Ewing, Laura Tall, Ben D. Boyer, Marc S. Joseph, Sam W. Sapkota, Amy R. TI Diversity, distribution and antibiotic resistance of Enterococcus spp. recovered from tomatoes, leaves, water and soil on US Mid-Atlantic farms SO FOOD MICROBIOLOGY LA English DT Article DE Pre-harvest tomatoes; Enterococcus spp.; Enterococcus faecalis; Antibiotic resistance; Food safety; Soil; Water; Amplified fragment length polymorphism ID ANTIMICROBIAL RESISTANCE; MULTIPLEX PCR; FRESH PRODUCE; CASSELIFLAVUS; VIRULENCE; FOODS; IDENTIFICATION; POPULATIONS; MENINGITIS; DISPERSAL AB Antibiotic-resistant enterococci are important opportunistic pathogens and have been recovered from retail tomatoes. However, it is unclear where and how tomatoes are contaminated along the farm-to-fork continuum. Specifically, the degree of pre-harvest contamination with enterococci is unknown. We evaluated the prevalence, diversity and antimicrobial susceptibilities of enterococci collected from tomato farms in the Mid-Atlantic United States. Tomatoes, leaves, groundwater, pond water, irrigation ditch water, and soil were sampled and tested for enterococci using standard methods. Antimicrobial susceptibility testing was performed using the Sensititre microbroth dilution system. Enterococcus faecalis isolates were characterized using amplified fragment length polymorphism to assess dispersal potential. Enterococci (n = 307) occurred in all habitats and colonization of tomatoes was common. Seven species were identified: Enterococcus casseliflavus, E. faecalis, Enterococcus gallinarum, Enterococcus faecium, Enterococcus avis, Enterococcus hirae and Enterococcus raffinosus. E. casseliflavus predominated in soil and on tomatoes and leaves, and E. faecalis predominated in pond water. On plants, distance from the ground influenced presence of enterococci. E. faecalis from samples within a farm were more closely related than those from samples between farms. Resistance to rifampicin, quinupristin/dalfopristin, ciprofloxacin and levofloxacin was prevalent. Consumption of raw tomatoes as a potential exposure risk for antibiotic-resistant Enterococcus spp. deserves further attention. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Micallef, Shirley A.; Goldstein, Rachel E. Rosenberg; George, Ashish; Joseph, Sam W.; Sapkota, Amy R.] Univ Maryland, Sch Publ Hlth, Maryland Inst Appl Environm Hlth, College Pk, MD 20742 USA. [Ewing, Laura; Tall, Ben D.] US Food & Drug Adm FDA, Virulence Mech Branch, Div Virulence Assessment, OARSA,CFSAN, Laurel, MD 20708 USA. [Boyer, Marc S.] US Food & Drug Adm FDA, Off Food Def Commun & Emergency Response, CFSAN, College Pk, MD 20740 USA. RP Sapkota, AR (reprint author), Univ Maryland, Sch Publ Hlth, Maryland Inst Appl Environm Hlth, Room 2234P,SPH Bldg, College Pk, MD 20742 USA. EM ars@umd.edu RI Sapkota, Amy/A-6046-2011; OI Tall, Ben/0000-0003-0399-3629 FU University of Maryland; Joint Institute for Food Safety and Applied Nutrition (JIFSAN); Centers for Disease Control and Prevention (CDC) [5U01CI000310] FX The authors would like to thank Steve Rideout, Andrew J. Estrin and Cristina R. McClaughlin for their help in the planning stages of this project and the Virginia Institute for Marine Sciences for laboratory space during sampling. This research was supported by the University of Maryland, Joint Institute for Food Safety and Applied Nutrition (JIFSAN) and Grant/Cooperative Agreement Number 5U01CI000310 from the Centers for Disease Control and Prevention (CDC). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of CDC. NR 35 TC 19 Z9 20 U1 4 U2 76 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD DEC PY 2013 VL 36 IS 2 BP 465 EP 474 DI 10.1016/j.fm.2013.04.016 PG 10 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 226MF UT WOS:000325039700042 PM 24010630 ER PT J AU Kang, L Carter, R Darcy, K Kauderer, J Liao, SY AF Kang, Le Carter, Randy Darcy, Kathleen Kauderer, James Liao, Shu-Yuan TI A fast Monte Carlo expectation-maximization algorithm for estimation in latent class model analysis with an application to assess diagnostic accuracy for cervical neoplasia in women with atypical glandular cells SO JOURNAL OF APPLIED STATISTICS LA English DT Article DE adjusted information matrix; bootstrap standard errors; diagnostic accuracy; imperfect gold standard; latent class model; MCEM estimation ID EM ALGORITHM; MAXIMUM-LIKELIHOOD; CONDITIONAL DEPENDENCE; CYTOLOGIC DIAGNOSIS; INFORMATION MATRIX; GOLD STANDARD; UNITED-STATES; BINARY DATA; TESTS; PREVALENCE AB In this article, we use a latent class model (LCM) with prevalence modeled as a function of covariates to assess diagnostic test accuracy in situations where the true disease status is not observed, but observations on three or more conditionally independent diagnostic tests are available. A fast Monte Carlo expectation-maximization (MCEM) algorithm with binary (disease) diagnostic data is implemented to estimate parameters of interest; namely, sensitivity, specificity, and prevalence of the disease as a function of covariates. To obtain standard errors for confidence interval construction of estimated parameters, the missing information principle is applied to adjust information matrix estimates. We compare the adjusted information matrix-based standard error estimates with the bootstrap standard error estimates both obtained using the fast MCEM algorithm through an extensive Monte Carlo study. Simulation demonstrates that the adjusted information matrix approach estimates the standard error similarly with the bootstrap methods under certain scenarios. The bootstrap percentile intervals have satisfactory coverage probabilities. We then apply the LCM analysis to a real data set of 122 subjects from a Gynecologic Oncology Group study of significant cervical lesion diagnosis in women with atypical glandular cells of undetermined significance to compare the diagnostic accuracy of a histology-based evaluation, a carbonic anhydrase-IX biomarker-based test and a human papillomavirus DNA test. C1 [Kang, Le] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Carter, Randy] SUNY Buffalo, Dept Biostat, Buffalo, NY 14214 USA. [Carter, Randy] SUNY Buffalo, Inst Healthcare Informat, Buffalo, NY 14203 USA. [Carter, Randy; Darcy, Kathleen; Kauderer, James] GOG Stat & Data Ctr, Buffalo, NY 14263 USA. [Liao, Shu-Yuan] Univ Calif Irvine, Sch Med, Irvine, CA 92697 USA. RP Carter, R (reprint author), SUNY Buffalo, Dept Biostat, 3435 Main St, Buffalo, NY 14214 USA. EM rcarter@buffalo.edu FU National Cancer Institute; GOG Tissue Bank [CA 27469]; GOG Statistical and Data Center [CA 37517]; Research Participation Program at the Center for Devices and Radiological Health FX This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and the GOG Tissue Bank (CA 27469), and the GOG Statistical and Data Center (CA 37517). Le Kang 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 US Department of Energy and the US Food and Drug Administration. The authors would like to thank the anonymous referees for helpful discussions and comments that greatly improved the article. A supplementary R code to implement the fast MCEM algorithm described in this article and the real data example with patient ID information removed are available upon request. NR 51 TC 0 Z9 0 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0266-4763 J9 J APPL STAT JI J. Appl. Stat. PD DEC 1 PY 2013 VL 40 IS 12 BP 2699 EP 2719 DI 10.1080/02664763.2013.825704 PG 21 WC Statistics & Probability SC Mathematics GA 228PF UT WOS:000325198000010 PM 24163493 ER PT J AU Rosenberg, AS Roivainen, M Hovi, T Liu, Q Murphy, PM AF Rosenberg, A. S. Roivainen, M. Hovi, T. Liu, Q. Murphy, P. M. TI CCR5 Deficiency and Severe Polio Infection in the 1984 Outbreak in Finland SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE poliovirus; CCR5delta32; neuropathology ID NILE-VIRUS-INFECTION; CHEMOKINE RECEPTORS; POLIOMYELITIS AB CCR5, a leukocyte chemoattractant receptor for chemokines CCL3, CCL4, and CCL5, promotes innate and adaptive immune responses by mediating leukocyte trafficking within lymph nodes and to peripheral tissues and is also known as a co-receptor for HIV cell entry. Homozygous inheritance of a complete loss-of-function mutation in CCR5 (CCR532/CCR532) is associated with symptomatic neuroinflammatory disease in humans with West Nile and Tickborne Encephalitis flavivirus infections. This study sought to establish whether CCR5 deficiency could also be a determinant of clinical outcome after infection by poliovirus which results in central nervous system damage in only a small proportion of cases. We analyzed serum samples from seven patients and 79 controls, collected during the 1984-1985 polio outbreak in Finland, where CCR532 is relatively common in the general population. The results excluded CCR5 deficiency as the sole determinant of severe neurologic disease after poliovirus infection in this population. J. Med. Virol. 85:2139-2140, 2013. (c) 2013 Wiley Periodicals, Inc. C1 [Rosenberg, A. S.] US FDA, Div Therapeut Prot, Off Biotechnol Prod, CDER, Silver Spring, MD USA. [Roivainen, M.; Hovi, T.] Natl Inst Hlth & Welf THL, Dept Infect Dis Surveillance & Control, Virol Unit, Helsinki, Finland. [Liu, Q.; Murphy, P. M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Rosenberg, AS (reprint author), US FDA, Div Therapeut Prot, Off Biotechnol Prod, CDER, Silver Spring, MD USA. EM amy.rosenberg@fda.hhs.gov NR 10 TC 0 Z9 0 U1 0 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD DEC PY 2013 VL 85 IS 12 BP 2139 EP 2140 DI 10.1002/jmv.23739 PG 2 WC Virology SC Virology GA 227ZE UT WOS:000325153400012 PM 24037958 ER PT J AU Kang, L Xiong, CJ Tian, LL AF Kang, Le Xiong, Chengjie Tian, Lili TI Estimating confidence intervals for the difference in diagnostic accuracy with three ordinal diagnostic categories without a gold standard SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE EM algorithm; Generalized pivot; Gold standard; Parametric bootstrap; Volume under the ROC surface ID ROC ANALYSIS; CHOICE AB With three ordinal diagnostic categories, the most commonly used measures for the overall diagnostic accuracy are the volume under the ROC surface (VUS) and partial volume under the ROC surface (PVUS), which are the extensions of the area under the ROC curve (AUC) and partial area under the ROC curve (PAUC), respectively. A gold standard (GS) test on the true disease status is required to estimate the VUS and PVUS. However, oftentimes it may be difficult, inappropriate, or impossible to have a GS because of misclassification error, risk to the subjects or ethical concerns. Therefore, in many medical research studies, the true disease status may remain unobservable. Under the normality assumption, a maximum likelihood (ML) based approach using the expectation-maximization (EM) algorithm for parameter estimation is proposed. Three methods using the concepts of generalized pivot and parametric/nonparametric bootstrap for confidence interval estimation of the difference in paired VUSs and PVUSs without a GS are compared. The coverage probabilities of the investigated approaches are numerically studied. The proposed approaches are then applied to a real data set of 118 subjects from a cohort study in early stage Alzheimer's disease (AD) from the Washington University Knight Alzheimer's Disease Research Center to compare the overall diagnostic accuracy of early stage AD between two different pairs of neuropsychological tests. (C) 2013 Elsevier B.V. All rights reserved. C1 [Kang, Le] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Xiong, Chengjie] Washington Univ, Div Biostat, St Louis, MO 63110 USA. [Tian, Lili] SUNY Buffalo, Dept Biostat, Buffalo, NY 14214 USA. RP Tian, LL (reprint author), SUNY Buffalo, Dept Biostat, 706 Kimball Tower,3435 Main St, Buffalo, NY 14214 USA. EM ltian@buffalo.edu FU National Institute on Aging [P50 AG05681, P01 AG03991, R01 AG034119] FX This study was partly supported by National Institute on Aging grant P50 AG05681, P01 AG03991, and R01 AG034119 for Dr. Chengjie Xiong. The opinions expressed are those of the authors and not necessarily those of the Editors. The authors thank the referees for helpful discussions and comments. NR 19 TC 1 Z9 1 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 EI 1872-7352 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD DEC PY 2013 VL 68 BP 326 EP 338 DI 10.1016/j.csda.2013.07.007 PG 13 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 225NA UT WOS:000324968400022 ER PT J AU Rong, ZM Alayash, AI Wilson, MT Cooper, CE AF Rong, Zimei Alayash, Abdu I. Wilson, Michael T. Cooper, Chris E. TI Modulating hemoglobin nitrite reductase activity through allostery: A mathematical model SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE Nitrite; Nitric oxide; Hemoglobin; Nitrite reductase activity; Kinetics; Fetal ID HUMAN CIRCULATION; OXIDE; OXYGEN; NO; PHYSIOLOGY; VASODILATION; CONTRIBUTES; SYNTHASES; BIOLOGY; FETAL AB The production of nitric oxide by hemoglobin (Hb) has been proposed to play a major role in the control of blood flow. Because of the allosteric nature of hemoglobin, the nitrite reductase activity is a complex function of oxygen partial pressure P-O2. We have previous developed a model to obtain the micro rate constants for nitrite reduction by R state (k(R)) and T state (k(T)) hemoglobin in terms of the experimental maximal macro rate constant k(Nmax) and the corresponding oxygen concentration P-O2max. However, because of the intrinsic difficulty in obtaining accurate macro rate constant k(N), from available experiments, we have developed an alternative method to determine the micro reaction rate constants (k(R) and k(T)) by fitting the simulated macro reaction rate curve (k(N) versus P-O2) to the experimental data. We then use our model to analyze the effect of pH (Bohr Effect) and blood ageing on the nitrite reductase activity, showing that the fall of bisphosphoglycerate (BPG) during red cell storage leads to increase NO production. Our model can have useful predictive and explanatory power. For example, the previously described enhanced nitrite reductase activity of ovine fetal Hb, in comparison to the adult protein, may be understood in terms of a weaker interaction with BPG and an increase in the value of k(T) from 0.0087 M(-1)s(-1) to 0.083 M(-1)s(-1). (C) 2013 Elsevier Inc. All rights reserved. C1 [Rong, Zimei; Wilson, Michael T.; Cooper, Chris E.] Univ Essex, Sch Biol Sci, Colchester CO4 3SQ, Essex, England. [Alayash, Abdu I.] US FDA, Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA. [Rong, Zimei] Univ Nottingham Ningbo China, Ctr English Language Educ, Ningbo 315100, Zhejiang, Peoples R China. RP Rong, ZM (reprint author), Univ Essex, Sch Biol Sci, Wivenhoe Pk, Colchester CO4 3SQ, Essex, England. EM zrong@essex.ac.uk; Abdu.Alayash@fda.nhs.gov; wilsmt@essex.ac.uk; ccooper@essex.ac.uk OI Rong, Zimei/0000-0002-7642-3160; Cooper, Chris/0000-0003-0381-3990 FU Leverhulme Trust [F/00 213/T]; National Institutes of Health (NIH) [HL110900]; U.S. Food and Drug Administration [MODSCI 2012] FX This work is financially supported by the Leverhulme Trust (F/00 213/T).; The authors acknowledge the expert assistance of Francine Wood in performing oxygen equilibrium curves and Drs. M. P. Gelderman (CBER/FDA) and M. H. Yazer (University of Pittsburgh) for providing and processing blood samples used in this study. This work was supported in part by The National Institutes of Health (NIH) under grants HL110900 and the U.S. Food and Drug Administration (MODSCI 2012) (AIA). NR 26 TC 1 Z9 1 U1 1 U2 11 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 NOV 30 PY 2013 VL 35 BP 193 EP 198 DI 10.1016/j.niox.2013.10.007 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 270IP UT WOS:000328312400024 PM 24177061 ER PT J AU Gupta, A Khan, MA AF Gupta, Abhay Khan, Mansoor A. TI Challenges of pediatric formulations: A FDA science perspective SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Editorial Material C1 [Gupta, Abhay; Khan, Mansoor A.] US FDA, Ctr Drug Evaluat & Res, Div Prod Qual Res, Silver Spring, MD 20993 USA. RP Khan, MA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Prod Qual Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM mansoor.khan@fda.hhs.gov NR 6 TC 0 Z9 0 U1 1 U2 6 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 2013 VL 457 IS 1 BP 346 EP 348 DI 10.1016/j.ijpharm.2013.08.064 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 248FU UT WOS:000326681800041 PM 24216242 ER PT J AU Ou, W Li, PJ Reiser, J AF Ou, Wu Li, Pingjuan Reiser, Jakob TI Targeting of Herpes Simplex Virus 1 Thymidine Kinase Gene Sequences into the OCT4 Locus of Human Induced Pluripotent Stem Cells SO PLOS ONE LA English DT Article ID SUICIDE GENE; GANCICLOVIR RESISTANCE; REGULATORY CIRCUITRY; SELECTIVE ABLATION; TUMOR-FORMATION; IN-VITRO; EXPRESSION; TRANSPLANTATION; DIFFERENTIATION; SURVIVAL AB The in vitro differentiation of human induced pluripotent stem cells (hiPSC) to generate specific types of cells is inefficient, and the remaining undifferentiated cells may form teratomas. This raises safety concerns for clinical applications of hiPSC-derived cellular products. To improve the safety of hiPSC, we attempted to site-specifically insert a herpes simplex virus 1 thymidine kinase (HSV1-TK) suicide gene at the endogenous OCT4 (POU5F1) locus of hiPSC. Since the endogenous OCT4 promoter is active in undifferentiated cells only, we speculated that the HSV1-TK suicide gene will be transcribed in undifferentiated cells only and that the remaining undifferentiated cells can be depleted by treating them with the prodrug ganciclovir (GCV) prior to transplantation. To insert the HSV1-TK gene at the OCT4 locus, we cotransfected hiPSC with a pair of plasmids encoding an OCT4-specific zinc finger nuclease (ZFN) and a donor plasmid harboring a promoter-less transgene cassette consisting of HSV1-TK and puromycin resistance gene sequences, flanked by OCT4 gene sequences. Puromycin resistant clones were established and characterized regarding their sensitivity to GCV and the site of integration of the HSV1-TK/puromycin resistance gene cassette. Of the nine puromycin-resistant iPSC clones analyzed, three contained the HSV1-TK transgene at the OCT4 locus, but they were not sensitive to GCV. The other six clones were GCV-sensitive, but the TK gene was located at off-target sites. These TK-expressing hiPSC clones remained GCV sensitive for up to 90 days, indicating that TK transgene expression was stable. Possible reasons for our failed attempt to selectively target the OCT4 locus are discussed. C1 [Ou, Wu; Li, Pingjuan; Reiser, Jakob] US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Reiser, J (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. EM Jakob.Reiser@fda.hhs.gov FU FDA Medical Countermeasures Initiative (MCMi) grant; U.S. Department of Energy; U.S. Food and Drug Administration FX This study was supported by an FDA Medical Countermeasures Initiative (MCMi) grant. This project was supported in part by an appointment of PL to the Research Participation Program at the Center for Biologics 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. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 3 Z9 4 U1 0 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 29 PY 2013 VL 8 IS 11 AR e81131 DI 10.1371/journal.pone.0081131 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 261MX UT WOS:000327670300024 PM 24312266 ER PT J AU Najafi, A Ghafourian, K Paixao, A Aljaabari, M Canos, D Asch, F Panza, J Cooper, HA AF Najafi, Amir Ghafourian, Kambiz Paixao, Andre Aljaabari, Mohamed Canos, Daniel Asch, Federico Panza, Julio Cooper, Howard A. TI Diagnosis of Cardiogenic Shock Without the Use of a Pulmonary Artery Catheter SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Shock, cardiogenic; Noninvasive cardiac imaging; Echocardiography C1 [Najafi, Amir; Ghafourian, Kambiz; Asch, Federico; Panza, Julio; Cooper, Howard A.] MedStar Heart Inst, Washington, DC USA. [Paixao, Andre; Aljaabari, Mohamed] MedStar Washington Hosp Cntr, Washington, DC USA. [Canos, Daniel] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 16279 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162905455 ER PT J AU Tereshchenko, LG Rizzi, P Mewton, N Jardim, GV Murthy, S Strauss, D Liu, CY Marchlinski, F Spooner, P Berger, R Kellman, P Lima, J AF Tereshchenko, Larisa G. Rizzi, Patricia Mewton, Nathan Jardim, Gustavo Volpe Murthy, Sindhoora Strauss, David Liu, Chia-Yiang Marchlinski, Francis Spooner, Peter Berger, Ronald Kellman, Peter Lima, Joao TI Infiltrated Atrial Fat Characterizes Underlying Atrial Fibrillation Substrate in Patients at Risk SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Cardiac MRI; Atrial fibrillation C1 [Tereshchenko, Larisa G.; Rizzi, Patricia; Mewton, Nathan; Jardim, Gustavo Volpe; Liu, Chia-Yiang; Spooner, Peter; Berger, Ronald; Lima, Joao] Johns Hopkins Univ Som, Baltimore, MD USA. [Murthy, Sindhoora] Johns Hopkins Univ, Baltimore, MD USA. [Strauss, David] US FDA, Silver Spring, MD USA. [Marchlinski, Francis] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Kellman, Peter] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 12402 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162902224 ER PT J AU Zusterzeel, R Canos, D Sanders, W Silverman, H MaCurdy, T Worrall, C Kelman, J Strauss, D AF Zusterzeel, Robbert Canos, Daniel Sanders, William Silverman, Henry MaCurdy, Thomas Worrall, Christopher Kelman, Jeffrey Strauss, David TI Cardiac Resynchronization Therapy is Associated With Increased Mortality in Right Bundle Branch Block Patients SO CIRCULATION LA English DT Meeting Abstract CT Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association CY NOV 16-17, 2013 CL Dallas, TX SP Amer Heart Assoc DE Resynchronization therapy; Bi-ventricular pacing; Heart failure C1 [Zusterzeel, Robbert; Canos, Daniel; Sanders, William; Strauss, David] US FDA, Cntr Devices & Radiol Hlth, Silver Spring, MD USA. [Silverman, Henry] Acumen LLC, Burlingame, CA USA. [MaCurdy, Thomas] Acumen LLC, Rsch, Burlingame, CA USA. [Worrall, Christopher; Kelman, Jeffrey] Cntrs Medicare & Medicaid Serv, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 26 PY 2013 VL 128 IS 22 SU S MA 15233 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC0CR UT WOS:000332162904462 ER PT J AU Sullivan, HW O'Donoghue, AC Aikin, KJ AF Sullivan, Helen W. O'Donoghue, Amie C. Aikin, Kathryn J. TI Presenting Quantitative Information About Placebo Rates to Patients SO JAMA INTERNAL MEDICINE LA English DT Letter ID TRIALS C1 [Sullivan, Helen W.; O'Donoghue, Amie C.; Aikin, Kathryn J.] Food & Drug Adm, Ctr Drug Evaluat & Res, Off Prescript Drug Promot, Silver Spring, MD 20993 USA. RP Sullivan, HW (reprint author), Food & Drug Adm, Ctr Drug Evaluat & Res, Off Prescript Drug Promot, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM helensullivan@fda.hhs.gov NR 6 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD NOV 25 PY 2013 VL 173 IS 21 DI 10.1001/jamainternmed.2013.10399 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AA2WG UT WOS:000330954300013 PM 24126622 ER PT J AU Slavov, SH Pearce, BA Buzatu, DA Wilkes, JG Beger, RD AF Slavov, Svetoslav H. Pearce, Bruce A. Buzatu, Dan A. Wilkes, Jon G. Beger, Richard D. TI Complementary PLS and KNN algorithms for improved 3D-QSDAR consensus modeling of AhR binding SO JOURNAL OF CHEMINFORMATICS LA English DT Article DE QSAR; Molecular descriptors; Quantitative spectral data-activity relationship (3D-QSDAR); Estrogen receptor binding; Molecular modeling ID DIBENZO-P-DIOXINS; POLYCHLORINATED DIBENZOFURANS; BIPHENYLS BINDING; TOXICITY; QSAR; DESCRIPTORS; PREDICTION; DFT AB Multiple validation techniques (Y-scrambling, complete training/test set randomization, determination of the dependence of R-test(2) on the number of randomization cycles, etc.) aimed to improve the reliability of the modeling process were utilized and their effect on the statistical parameters of the models was evaluated. A consensus partial least squares (PLS)-similarity based k-nearest neighbors (KNN) model utilizing 3D-SDAR (three dimensional spectral data-activity relationship) fingerprint descriptors for prediction of the log(1/EC50) values of a dataset of 94 aryl hydrocarbon receptor binders was developed. This consensus model was constructed from a PLS model utilizing 10 ppm x 10 ppm x 0.5 angstrom bins and 7 latent variables (R-test(2) of 0.617), and a KNN model using 2 ppm x 2 ppm x 0.5 angstrom bins and 6 neighbors (R-test(2) of 0.622). Compared to individual models, improvement in predictive performance of approximately 10.5% (R-test(2) of 0.685) was observed. Further experiments indicated that this improvement is likely an outcome of the complementarity of the information contained in 3D-SDAR matrices of different granularity. For similarly sized data sets of Aryl hydrocarbon (AhR) binders the consensus KNN and PLS models compare favorably to earlier reports. The ability of 3D-QSDAR (three dimensional quantitative spectral data-activity relationship) to provide structural interpretation was illustrated by a projection of the most frequently occurring bins on the standard coordinate space, thus allowing identification of structural features related to toxicity. C1 [Slavov, Svetoslav H.; Pearce, Bruce A.; Buzatu, Dan A.; Wilkes, Jon G.; Beger, Richard D.] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Beger, RD (reprint author), US FDA, Div Syst Biol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Richard.Beger@fda.hhs.gov FU F.D.A. FX The authors thank F.D.A. for the financial support. NR 31 TC 10 Z9 10 U1 0 U2 21 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-2946 J9 J CHEMINFORMATICS JI J. Cheminformatics PD NOV 21 PY 2013 VL 5 AR 47 DI 10.1186/1758-2946-5-47 PG 16 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 283DR UT WOS:000329226000001 PM 24257141 ER PT J AU Young, WM South, P Begley, TH Noonan, GO AF Young, Wendy M. South, Paul Begley, Timothy H. Noonan, Gregory O. TI Determination of Perfluorochemicals in Fish and Shellfish Using Liquid Chromatography-Tandem Mass Spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE perfluorochemicals; method validation; fish; shellfish ID PERFLUORINATED COMPOUNDS; HUMAN EXPOSURE; PERFLUOROALKYL ACIDS; FOOD SIMULANTS; POPULATION; PERFLUOROOCTANESULFONATE; PERFLUOROCARBOXYLATES; MIGRATION; CHEMICALS; WATER AB This paper reports the validation and application of a method for determination of 10 perfluorochemicals (PFCs) in retail fish and shellfish. The analytes of interest were 7 perfluorinated carboxylates and 3 perfluorinated sulfonates. Fish and shellfish samples were digested with a basic solution of 10 mM sodium hydroxide in methanol before sonication and solid phase extraction through weak anion exchange. Analysis was performed using liquid chromatography tandem mass spectrometry. Recoveries from spiking five different types of fish and shellfish indicate that the method performs similarly with different fish types, and recoveries were over 90% for all analytes. Forty-six retail samples, collected between 2010 and 2012, including 13 different types of fish and shellfish were analyzed for PFCs. The 13 different types included the top 10 most-consumed fish and shellfish in the United States according to data collected by the National Fisheries Institute. Two Standard Reference Materials were also analyzed. Most fish and shellfish had no detected PFCs; only 11 samples of the 46 tested had detectable concentrations of PFCs. C1 [Young, Wendy M.; South, Paul; Begley, Timothy H.; Noonan, Gregory O.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Young, WM (reprint author), 5100 Paint Branch Pkwy,HFS 706, College Pk, MD 20740 USA. EM wendy.young@fda.hhs.gov NR 29 TC 3 Z9 3 U1 3 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 NOV 20 PY 2013 VL 61 IS 46 BP 11166 EP 11172 DI 10.1021/jf403935g PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 253QC UT WOS:000327103400040 PM 24144282 ER PT J AU Lei, HY Li, TW Hung, GC Li, BJ Tsai, S Lo, SC AF Lei, Haiyan Li, Tianwei Hung, Guo-Chiuan Li, Bingjie Tsai, Shien Lo, Shyh-Ching TI Identification and characterization of EBV genomes in spontaneously immortalized human peripheral blood B lymphocytes by NGS technology SO BMC GENOMICS LA English DT Article DE Epstein Barr Virus; Mycoplasma; Next-generation sequencing; Human immortalized B lymphocytes ID EPSTEIN-BARR-VIRUS; NASOPHARYNGEAL CARCINOMA; GASTRIC-CARCINOMA; VIRAL GENOMES; DNA-SEQUENCE; CELLS; LYMPHOMA; BIOPSIES AB Background: We conducted genomic sequencing to identify Epstein Barr Virus (EBV) genomes in 2 human peripheral blood B lymphocytes that underwent spontaneous immortalization promoted by mycoplasma infections in culture, using the high-throughput sequencing (HTS) Illumina MiSeq platform. The purpose of this study was to examine if rapid detection and characterization of a viral agent could be effectively achieved by HTS using a platform that has become readily available in general biology laboratories. Results: Raw read sequences, averaging 175 bps in length, were mapped with DNA databases of human, bacteria, fungi and virus genomes using the CLC Genomics Workbench bioinformatics tool. Overall 37,757 out of 49,520,834 total reads in one lymphocyte line (# K4413-Mi) and 28,178 out of 45,335,960 reads in the other lymphocyte line (# K4123-Mi) were identified as EBV sequences. The two EBV genomes with estimated 35.22-fold and 31.06-fold sequence coverage respectively, designated K4413-Mi EBV and K4123-Mi EBV (GenBank accession number KC440852 and KC440851 respectively), are characteristic of type-1 EBV. Conclusions: Sequence comparison and phylogenetic analysis among K4413-Mi EBV, K4123-Mi EBV and the EBV genomes previously reported to GenBank as well as the NA12878 EBV genome assembled from database of the 1000 Genome Project showed that these 2 EBVs are most closely related to B95-8, an EBV previously isolated from a patient with infectious mononucleosis and WT-EBV. They are less similar to EBVs associated with nasopharyngeal carcinoma (NPC) from Hong Kong and China as well as the Akata strain of a case of Burkitt's lymphoma from Japan. They are most different from type 2 EBV found in Western African Burkitt's lymphoma. C1 [Lei, Haiyan; Li, Tianwei; Hung, Guo-Chiuan; Li, Bingjie; Tsai, Shien; Lo, Shyh-Ching] Food & Drug Adm, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Tissue Microbiol Lab,Off Cellular Tissue & Gene T, Bethesda, MD 20892 USA. RP Lo, SC (reprint author), Food & Drug Adm, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Tissue Microbiol Lab,Off Cellular Tissue & Gene T, NIH Bldg 29B,Rm 1NN06,29 Lincoln Dr, Bethesda, MD 20892 USA. EM ShyhChing.Lo@fda.hhs.gov FU FDA Modernizing Science research grant; U.S. Department of Energy; U.S. Food and Drug Administration FX The study was supported in part by FDA Modernizing Science research grant and supported in part by an appointment to the Research Participation Program at the CBER of FDA 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 17 Z9 18 U1 1 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD NOV 19 PY 2013 VL 14 AR 804 DI 10.1186/1471-2164-14-804 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 274YM UT WOS:000328642100005 PM 24252203 ER PT J AU Yamazaki, A Wu, CL Cheng, WC Badano, A AF Yamazaki, Asumi Wu, Chih-Lei Cheng, Wei-Chung Badano, Aldo TI Spatial resolution and noise in organic light-emitting diode displays for medical imaging applications SO OPTICS EXPRESS LA English DT Article ID LIQUID-CRYSTAL DISPLAYS; VIEWING ANGLE; CONTRAST; DEVICES; 5-MILLION-PIXEL; PERFORMANCE; RADIOLOGY; IMAGES; POWER; IPAD AB We report on the resolution and noise characteristics of handheld and workstation organic light-emitting diode (OLED) displays in comparison with liquid crystal displays (LCDs). The results demonstrate advantages, in terms of sharpness, of handheld OLED displays with modulation transfer function (MTF) values exceeding 0.60 at the Nyquist frequencies. The OLED workstation included in this study exhibits significant signal contamination among adjacent pixels resulting in degraded resolution performance indicated by horizontal and vertical MTF values of 0.13 and 0.24 at the Nyquist frequency. On the other hand, its noise characteristics are superior to the LCD workstation tested. While the noise power spectral (NPS) values of the OLED workstation are 8.0x10(-6) mm(2) at 1 mm(-1), the LCD workstation has NPS values of 2.6x10(-5) mm(2). Although phone-size OLED displays have superior resolution and noise per pixel, the perceived resolution characteristics at appropriate viewing distances are inferior to tablet-size and workstation LCDs. In addition, our results show some degree of dependency of the resolution and noise on luminance level and viewing orientation. We also found a slightly degraded resolution and increased low-frequency noise at off-normal orientations in the handheld displays. (C) 2013 Optical Society of America C1 [Yamazaki, Asumi; Wu, Chih-Lei; Cheng, Wei-Chung; Badano, Aldo] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Yamazaki, Asumi] Nagoya Univ, Grad Sch Med Sci, Nagoya, Aichi 4618673, Japan. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM Aldo.Badano@fda.hhs.gov RI Cheng, Wei-Chung/E-6240-2014; OI badano, aldo/0000-0003-3712-6670 FU U.S. DOE; U.S. FDA FX AY and CW acknowledge funding by appointments to the Research Participation Program at the CDRH administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. DOE and the U.S. FDA. The mention of commercial products herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services. This is a contribution of the FDA and is not subject to copyright. NR 28 TC 2 Z9 2 U1 2 U2 18 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 NOV 18 PY 2013 VL 21 IS 23 BP 28111 EP 28133 DI 10.1364/OE.21.028111 PG 23 WC Optics SC Optics GA 258YG UT WOS:000327494000055 PM 24514325 ER PT J AU Xu, XM Siddiqui, A Khan, MA AF Xu, Xiaoming Siddiqui, Akhtar Khan, Mansoor A. TI Focused beam reflectance measurement to monitor nimodipine precipitation process SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Nimodipine; Crystallization; Focused beam reflectance measurement; Moisture content; Liquid-filled capsule AB Crystallization of nimodipine in liquid-filled soft gelatin capsule during storage was reported for some commercial products, resulting in product recalls due to product quality and more importantly safety concerns. In this study, a real time particle monitoring tool, focused beam reflectance measurement, was used to evaluate the precipitation conditions of nimodipine in co-solvents. Upon water addition, two particle populations were discovered, appearing at different percentage of water content. Two transitions (i.e. sudden increase in particle counts) were observed, possibility related to nucleation and crystal growth of nimodipine. Furthermore, lowering storage temperature increased the tendency of nimodipine precipitation. Most critically, it was determined that with certain excipient, the drug precipitation occurred at approximately 7% (w/w) water content. Considering that all the orally administered liquid filled soft gelatin capsule shells contain residue water content as plasticizer, moisture transfer from the shell to the formulation may occur during long term storage, resulting in drug precipitation, particularly under cold temperature conditions. Published by Elsevier B.V. C1 [Xu, Xiaoming; Siddiqui, Akhtar; Khan, Mansoor A.] US FDA, Div Prod Qual Res, OTR OPS, Silver Spring, MD 20993 USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, OTR OPS, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Xiaoming.Xu@fda.hhs.gov; Akhtar.Siddiqui@fda.hhs.gov; Mansoor.Khan@fda.hhs.gov OI Xu, Xiaoming/0000-0003-1672-0830 NR 9 TC 4 Z9 4 U1 0 U2 8 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 18 PY 2013 VL 456 IS 2 BP 353 EP 356 DI 10.1016/j.ijpharm.2013.08.083 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 234LC UT WOS:000325644600011 PM 24016702 ER PT J AU Rahman, Z Khan, MA AF Rahman, Ziyaur Khan, Mansoor A. TI Hunter screening design to understand the product variability of solid dispersion formulation of a peptide antibiotic SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Vancomycin; Polyethylene glycol; Dissolution; Potency; Design of experiment ID COLON-SPECIFIC DELIVERY; LOADED PLGA NANOPARTICLES; CAPSULE FORMULATIONS; VANCOMYCIN; STABILITY; BIOAVAILABILITY; DISSOLUTION; RELEASE; SYSTEM; DRUGS AB The focus of present research was to understand and control the variability of solid dispersion (SD) formulation of non-ribosomal peptide antibiotic, vancomycin (VCM). Hunter screening design was constructed using seven independent variables namely melting temperature (X-1), congealing temperature (X-2), mixing time (X-3), type of capsule shell (X-4), filling method (X-5), molecular weight of polyethylene glycol (PEG, X-6) and surfactant type (X-7), and responses measured were cumulative percentage of VCM released in 45 min (Y-1) and potency (Y-2). The SD formulations were prepared by melt-fusion method, and tested for dissolution, potency, and characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and near infrared chemical imaging (NIR-CI). Statistically significant (p < 0.05) effect of congealing temperature (X-2), type of capsule shell (X-4), filling method (X-5), molecular weight of PEG (X-6) was revealed on Y-1, and R-2 of 0.992 was obtained between experimental and predicted value. None of the factors have statistically significant (p > 0.05) influence on Y-2. SEM, DSC and PXRD indicated crystalline nature of SD formulations. Homogeneity of SD formulations was shown by NIR-CI images. In summary, the quality of VCM SD formulations could be assured by controlling the critical factors during manufacturing. Published by Elsevier B.V. C1 [Rahman, Ziyaur; Khan, Mansoor A.] US FDA, Ctr Drug Evaluat & Res, Div Prod Qual & Res, Rockville, MD 20857 USA. RP Khan, MA (reprint author), 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 NR 36 TC 5 Z9 5 U1 1 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 18 PY 2013 VL 456 IS 2 BP 572 EP 582 DI 10.1016/j.ijpharm.2013.07.062 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 234LC UT WOS:000325644600038 PM 23994761 ER PT J AU Ning, YMM Pierce, W Maher, VE Karuri, S Tang, SH Chiu, HJ Palmby, T Zirkelbach, JF Marathe, D Mehrotra, N Liu, Q Ghosh, D Cottrell, CL Leighton, J Sridhara, R Ibrahim, A Justice, R Pazdur, R AF Ning, Yangmin M. Pierce, William Maher, V. Ellen Karuri, Stella Tang, Sheng-Hui Chiu, Haw-Jyh Palmby, Todd Zirkelbach, Jeanne Fourie Marathe, Dhananjay Mehrotra, Nitin Liu, Qi Ghosh, Debasis Cottrell, Christy L. Leighton, John Sridhara, Rajeshwari Ibrahim, Amna Justice, Robert Pazdur, Richard TI Enzalutamide for Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer Who Have Previously Received Docetaxel: U.S. Food and Drug Administration Drug Approval Summary SO CLINICAL CANCER RESEARCH LA English DT Article ID INCREASED SURVIVAL; PREDNISONE; MITOXANTRONE; ABIRATERONE; TRIAL AB This article summarizes the regulatory evaluation that led to the full approval of enzalutamide (XTANDI, Medivation Inc.) by the U. S. Food and Drug Administration (FDA) on August 31, 2012, for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel. This approval was based on the results of a randomized, placebo-controlled trial which randomly allocated 1,199 patients with mCRPC who had received prior docetaxel to receive either enzalutamide, 160 mg orally once daily (n = 800), or placebo (n = 399). All patients were required to continue androgen deprivation therapy. The primary endpoint was overall survival. At the prespecified interim analysis, a statistically significant improvement in overall survival was demonstrated for the enzalutamide arm compared with the placebo arm [HR = 0.63; 95% confidence interval: 0.53-0.75; P < 0.0001]. The median overall survival durations were 18.4 months and 13.6 months in the enzalutamide and placebo arms, respectively. The most common adverse reactions (>= 10%) included asthenia or fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, and upper respiratory infection. Seizures occurred in 0.9% of patients on enzalutamide compared with no patients on the placebo arm. Overall, the FDA's review and analyses of the submitted data confirmed that enzalutamide had a favorable benefit-risk profile in the study patient population, thus supporting its use for the approved indication. The recommended dose is 160 mg of enzalutamide administered orally once daily. Enzalutamide represents the third product that the FDA has approved in the same disease setting within a period of 2 years. (C) 2013 AACR. C1 [Ning, Yangmin M.; Pierce, William; Maher, V. Ellen; Chiu, Haw-Jyh; Palmby, Todd; Cottrell, Christy L.; Leighton, John; Ibrahim, Amna; Justice, Robert; Pazdur, Richard] US FDA, Off Hematol & Oncol Prod, Off New Drugs, Silver Spring, MD 20993 USA. [Karuri, Stella; Tang, Sheng-Hui; Sridhara, Rajeshwari] US FDA, Off Biostat, Silver Spring, MD 20993 USA. [Zirkelbach, Jeanne Fourie; Marathe, Dhananjay; Mehrotra, Nitin; Liu, Qi] US FDA, Off Clin Pharmacol, Silver Spring, MD 20993 USA. [Ghosh, Debasis] US FDA, Off New Drug Qual Assessment, Silver Spring, MD 20993 USA. [Ghosh, Debasis] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Ning, YMM (reprint author), US FDA, Off Hematol & Oncol Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Room 2139, Silver Spring, MD 20993 USA. EM ningy@cder.fda.gov NR 14 TC 15 Z9 16 U1 0 U2 7 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 NOV 15 PY 2013 VL 19 IS 22 BP 6067 EP 6073 DI 10.1158/1078-0432.CCR-13-1763 PG 7 WC Oncology SC Oncology GA 256NU UT WOS:000327320900003 PM 24141628 ER PT J AU Mujat, M Ferguson, RD Iftimia, N Hammer, DX Nedyalkov, I Wosnik, M Legner, H AF Mujat, Mircea Ferguson, R. Daniel Iftimia, Nicusor Hammer, Daniel X. Nedyalkov, Ivaylo Wosnik, Martin Legner, Hartmut TI Optical coherence tomography-based micro-particle image velocimetry SO OPTICS LETTERS LA English DT Article ID DOPPLER TOMOGRAPHY AB We present a new application of optical coherence tomography (OCT), widely used in biomedical imaging, to flow analysis in near-wall hydrodynamics for marine research. This unique capability, called OCT micro-particle image velocimetry, provides a high-resolution view of microscopic flow phenomena and measurement of flow statistics within the first millimeter of a boundary layer. The technique is demonstrated in a small flow cuvette and in a water tunnel. (C) 2013 Optical Society of America C1 [Mujat, Mircea; Ferguson, R. Daniel; Iftimia, Nicusor; Hammer, Daniel X.; Legner, Hartmut] Phys Sci Inc, Andover, MA 01810 USA. [Hammer, Daniel X.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20902 USA. [Nedyalkov, Ivaylo; Wosnik, Martin] Univ New Hampshire, Dept Mech Engn, Durham, NH 03824 USA. RP Mujat, M (reprint author), Phys Sci Inc, 20 New England Business Ctr, Andover, MA 01810 USA. EM mujat@psicorp.com RI Wosnik, Martin/L-5632-2013 OI Wosnik, Martin/0000-0001-9290-3327 FU ONR SBIR [N00014-10-M-0180]; NSF-MRI [0821608] FX Support through ONR SBIR Phase 1 Contract No. N00014-10-M-0180 to H. Legner/PSI and NSF-MRI Award No. 0821608 to M. Wosnik/UNH is gratefully acknowledged. NR 11 TC 6 Z9 7 U1 1 U2 7 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 EI 1539-4794 J9 OPT LETT JI Opt. Lett. PD NOV 15 PY 2013 VL 38 IS 22 BP 4558 EP 4561 DI 10.1364/OL.38.004558 PG 4 WC Optics SC Optics GA 254DB UT WOS:000327142600010 PM 24322073 ER PT J AU Goyal, KG Dong, ML Nguemaha, VM Worth, BW Judge, PT Calhoun, WR Bali, LM Bali, S AF Goyal, K. G. Dong, M. L. Nguemaha, V. M. Worth, B. W. Judge, P. T. Calhoun, W. R. Bali, L. M. Bali, S. TI Empirical model of total internal reflection from highly turbid media SO OPTICS LETTERS LA English DT Article ID COMPLEX REFRACTIVE-INDEX; LIGHT-SCATTERING; EVANESCENT-WAVE; CRITICAL-ANGLE; LIQUIDS AB We demonstrate, to the best of our knowledge, a first accurate empirical model for reflectance measurements from highly turbid media over the full range of incident angles, i.e., for reflectivity values going from unity in the total internal reflection regime to nearly zero when almost all the light is transmitted. Evidence that our model is accurate is provided by extraction of the particle size, followed by independent verification with dynamic light scattering. Our methodology is in direct contrast with the prevalent approach in turbid media of focusing on only the critical angle region, which is just a small subset of the entire reflectance data. (C) 2013 Optical Society of America C1 [Goyal, K. G.; Dong, M. L.; Nguemaha, V. M.; Worth, B. W.; Judge, P. T.; Bali, L. M.; Bali, S.] Miami Univ, Dept Phys, Oxford, OH 45056 USA. [Calhoun, W. R.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Bali, S (reprint author), Miami Univ, Dept Phys, Oxford, OH 45056 USA. EM balis@miamioh.edu FU Petroleum Research Fund; Dillon-Kane, LLC FX Funding from Petroleum Research Fund and Dillon-Kane, LLC, is gratefully acknowledged. We thank Miami University's Instrumentation Lab for help with Labview. We are grateful to three anonymous referees whose insightful suggestions contributed immensely to this Letter. NR 19 TC 8 Z9 8 U1 1 U2 7 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 EI 1539-4794 J9 OPT LETT JI Opt. Lett. PD NOV 15 PY 2013 VL 38 IS 22 BP 4888 EP 4891 DI 10.1364/OL.38.004888 PG 4 WC Optics SC Optics GA 254DB UT WOS:000327142600095 PM 24322158 ER PT J AU Li, Q Guo, D Dong, ZQ Zhang, W Zhang, L Huang, SM Polli, JE Shu, Y AF Li, Qing Guo, Dong Dong, Zhongqi Zhang, Wei Zhang, Lei Huang, Shiew-Mei Polli, James E. Shu, Yan TI Ondansetron can enhance cisplatin-induced nephrotoxicity via inhibition of multiple toxin and extrusion proteins (MATEs) SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Cisplatin; Drug interaction; Multidrug and toxin extrusion protein; Nephrotoxicity; Ondansetron; Organic cation transporter ID ORGANIC CATION TRANSPORTERS; AGENT-INDUCED NEPHROTOXICITY; GENETIC-VARIATION; INDUCED EMESIS; HUMAN KIDNEY; MULTIDRUG; METFORMIN; CIMETIDINE; OCT2; MICE AB The nephrotoxicity limits the clinical application of cisplatin. Human organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATEs) work in concert in the elimination of cationic drugs such as cisplatin from the kidney. We hypothesized that co-administration of ondansetron would have an effect on cisplatin nephrotoxicity by altering the function of cisplatin transporters. The inhibitory potencies of ondansetron on metformin accumulation mediated by OCT2 and MATEs were determined in the stable HEK-293 cells expressing these transporters. The effects of ondansetron on drug disposition in vivo were examined by conducting the pharmacokinetics of metformin, a classical substrate for OCTs and MATEs, in wild-type and Mate1-/- mice. The nephrotoxicity was assessed in the wild-type and Mate1-/- mice received cisplatin with and without ondansetron. Both MATEs, including human MATE1, human MATE2-K, and mouse Mate1, and OCT2 (human and mouse) were subject to ondansetron inhibition, with much greater potencies by ondansetron on MATEs. Ondansetron significantly increased tissue accumulation and pharmacokinetic exposure of metformin in wild-type but not in Mate1-/- mice. Moreover, ondansetron treatment significantly enhanced renal accumulation of cisplatin and cisplatin-induced nephrotoxicity which were indicated by increased levels of biochemical and molecular biomarkers and more severe pathohistological changes in mice. Similar increases in nephrotoxicity were caused by genetic deficiency of MATE function in mice. Therefore, the potent inhibition of MATEs by ondansetron enhances the nephrotoxicity associated with cisplatin treatment in mice. Potential nephrotoxic effects of combining the chemotherapeutic cisplatin and the antiemetic 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, such as ondansetron, should be investigated in patients. (C) 2013 Elsevier Inc. All rights reserved. C1 [Li, Qing; Dong, Zhongqi; Zhang, Wei; Polli, James E.; Shu, Yan] Univ Maryland, Dept Pharmaceut Sci, Sch Pharm, Baltimore, MD 21201 USA. [Li, Qing; Guo, Dong; Zhang, Wei] Cent S Univ, Inst Clin Pharmacol, Changsha 410078, Hunan, Peoples R China. [Zhang, Lei; Huang, Shiew-Mei] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Shu, Y (reprint author), Univ Maryland, Dept Pharmaceut Sci, Sch Pharm, 20 Penn St,HSFII Room 555, Baltimore, MD 21201 USA. EM yshu@rx.umaryland.edu FU National Institute of General Medical Sciences of the National Institutes of Health (NIH) [R01GM099742]; US Food and Drug Administration (FDA) [U01FD004320]; National Natural Science Foundation (NNSF) of China [81001445, 81273595] FX The present study was supported by the National Institute of General Medical Sciences of the National Institutes of Health (NIH) under Award R01GM099742 (Y.S.) and by the US Food and Drug Administration (FDA) under Award U01FD004320 (J.E.P., Y.S.). Qing Li and Wei Zhang received research support from the National Natural Science Foundation (NNSF) of China (81001445, Q.L; 81273595, W.Z.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, FDA and NNSF. NR 51 TC 20 Z9 22 U1 1 U2 10 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 NOV 15 PY 2013 VL 273 IS 1 BP 100 EP 109 DI 10.1016/j.taap.2013.08.024 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 256DN UT WOS:000327290000012 PM 24001450 ER PT J AU Lin, ZM Fisher, JW Wang, R Ross, MK Filipov, NM AF Lin, Zhoumeng Fisher, Jeffrey W. Wang, Ran Ross, Matthew K. Filipov, Nikolay M. TI Estimation of placental and lactational transfer and tissue distribution of atrazine and its main metabolites in rodent dams, fetuses, and neonates with physiologically based pharmacokinetic modeling SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Atrazine; PBPK modeling; Pesticides; Developmental toxicity; Pregnancy; Lactation ID SPRAGUE-DAWLEY RATS; BLOOD PARTITION-COEFFICIENTS; MULTIROUTE EXPOSURE MODEL; IN-VITRO METABOLISM; N-OCTANOL-WATER; PREGNANT RAT; GUINEA-PIG; CYTOCHROME-P450 ENZYMES; POSTNATAL-DEVELOPMENT; TRICHLOROACETIC-ACID AB Atrazine (ATR) is a widely used chlorotriazine herbicide, a ubiquitous environmental contaminant, and a potential developmental toxicant. To quantitatively evaluate placental/lactational transfer and fetal/neonatal tissue dosimetry of ATR and its major metabolites, physiologically based pharmacokinetic models were developed for rat dams, fetuses and neonates. These models were calibrated using pharmacokinetic data from rat dams repeatedly exposed (oral gavage; 5 mg/kg) to ATR followed by model evaluation against other available rat data. Model simulations corresponded well to the majority of available experimental data and suggest that: (1) the fetus is exposed to both ATR and its major metabolite didealkylatrazine (DACT) at levels similar to maternal plasma levels, (2) the neonate is exposed mostly to DACT at levels two-thirds lower than maternal plasma or fetal levels, while lactational exposure to ATR is minimal, and (3) gestational carryover of DACT greatly affects its neonatal dosimetry up until mid-lactation. To test the model's cross-species extrapolation capability, a pharmacoldnetic study was conducted with pregnant C57BL/6 mice exposed (oral gavage; 5 mg/kg) to ATR from gestational day 12 to 18. By using mouse-specific parameters, the model predictions fitted well with the measured data, including placental ATR/DACT levels. However, fetal concentrations of DACT were overestimated by the model (10-fold). This overestimation suggests that only around 10% of the DACT that reaches the fetus is tissue-bound. These rodent models could be used in fetal/neonatal tissue dosimetry predictions to help design/interpret early life toxicity/ pharmacokinetic studies with ATR and as a foundation for scaling to humans. (C) 2013 Elsevier Inc. All rights reserved. C1 [Lin, Zhoumeng; Filipov, Nikolay M.] Univ Georgia, Dept Physiol & Pharmacol, Coll Vet Med, Athens, GA 30602 USA. [Lin, Zhoumeng; Filipov, Nikolay M.] Univ Georgia, Interdisciplinary Toxicol Program, Athens, GA 30602 USA. [Fisher, Jeffrey W.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Wang, Ran; Ross, Matthew K.] Mississippi State Univ, Coll Vet Med, Ctr Environm Hlth Sci, Dept Basic Sci, Mississippi State, MS 39762 USA. [Wang, Ran] Jiangsu Acad Agr Sci, Inst Food Safety, Nanjing 210014, Peoples R China. RP Filipov, NM (reprint author), Univ Georgia, Dept Physiol & Pharmacol, 501 DW Brooks Dr, Athens, GA 30602 USA. EM filipov@uga.edu OI Lin, Zhoumeng/0000-0002-8731-8366 NR 128 TC 13 Z9 13 U1 0 U2 25 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 NOV 15 PY 2013 VL 273 IS 1 BP 140 EP 158 DI 10.1016/jtaap.2013.08.010 PG 19 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 256DN UT WOS:000327290000016 PM 23958493 ER PT J AU Ferreira, TPT de Arantes, ACS do Nascimento, CVMF Olsen, PC Trentin, PG Rocco, PRM Hogaboam, CM Puri, RK Martins, MA Silva, PMRE AF Ferreira, Tatiana Paula T. de Arantes, Ana Carolina S. do Nascimento, Caio Victor M. F. Olsen, Priscilla C. Trentin, Patricia G. Rocco, Patricia R. M. Hogaboam, Cory M. Puri, Raj K. Martins, Marco Aurelio Rodrigues e Silva, Patricia Machado TI IL-13 Immunotoxin Accelerates Resolution of Lung Pathological Changes Triggered by Silica Particles in Mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INDUCED PULMONARY-FIBROSIS; PSEUDOMONAS EXOTOXIN; INTERLEUKIN-13 RECEPTOR; IL-13-RESPONSIVE CELLS; AIRWAY INFLAMMATION; SIGNAL-TRANSDUCTION; THERAPEUTIC TARGET; CARCINOMA-CELLS; LYMPH-NODES; T-CELLS AB Instillation of silica into the lungs of rodents results in pathological changes that strongly mimic human silicosis, an occupational lung disease marked by restrictive airway obstruction, inflammation, and fibrosis. Because IL-13 is a pivotal proinflammatory and fibro-genic cytokine, we examined whether a recombinant immunotoxin comprised of human IL-13 and a mutated form of Pseudomonas exotoxin (IL-13-PE) might affect pathological features of experimental silicosis. Mice received a single intranasal instillation of silica particles and were treated with intranasal IL-13-PE every other day from days 21 to 27 postsilica. The sensitivity of putative cell targets to IL-13-PE was also assessed in in vitro settings. Upregulation of IL-13, its receptor subunits IL-13R alpha 1 and IL-13R alpha 2, and shared receptor IL-4R alpha were associated with development of granulomatous lung inflammation triggered by silica. IL-13-PE inhibited silica-induced granuloma and fibrotic responses noted at 24 h and 15 d after the last treatment. Upregulation of TNF-alpha, TGF-beta, and chemokines, as well as increased collagen deposition and airway hyperreactivity to methacholine were all clearly sensitive to IL-13-PE. In addition, IL-13-PE inhibited both IL-13-induced proliferation of cultured lung fibroblasts from silicotic mice and silica-induced IL-8 generation from A549 cells. In conclusion, our findings show that therapeutic treatment with IL-13-PE can reverse important pathological features caused by inhalation of silica particles, suggesting that this recombinant immunotoxin is a promising molecular template in drug discovery for the treatment of silicosis. C1 [Ferreira, Tatiana Paula T.; de Arantes, Ana Carolina S.; do Nascimento, Caio Victor M. F.; Olsen, Priscilla C.; Trentin, Patricia G.; Martins, Marco Aurelio; Rodrigues e Silva, Patricia Machado] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Lab Inflammat, BR-21045900 Rio De Janeiro, Brazil. [Rocco, Patricia R. M.] Univ Fed Rio de Janeiro, Lab Pulm Invest, BR-21941901 Rio De Janeiro, Brazil. [Hogaboam, Cory M.] Univ Michigan, Dept Pathol, Sch Med, Ann Arbor, MI 48109 USA. [Puri, Raj K.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA. RP Silva, PMRE (reprint author), Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Lab Inflammat, Ave Brasil 4365, BR-21045900 Rio De Janeiro, Brazil. EM patmar@ioc.fiocruz.br RI Olsen, Priscilla/I-8994-2012; hogaboam, cory /M-3578-2014 FU Conselho Nacional de Desenvolvimento Cientifico and Tecnologico [CNPq-476470/2009-9]; Fundacao Carlos Chagas de Apoio a Pesquisa do Estado do Rio de Janeiro [FAPERJ-E-26/102.362/2009]; Programa de Auxilio a Pesquisa Estrategica em Saude [PAPES 5-305674/2009-9]; European Community's Seventh Framework Programme [HEALTH-F4-2011-281608] FX This work was supported by the Conselho Nacional de Desenvolvimento Cientifico and Tecnologico (Grant CNPq-476470/2009-9), Fundacao Carlos Chagas de Apoio a Pesquisa do Estado do Rio de Janeiro (Grant FAPERJ-E-26/102.362/2009), Programa de Auxilio a Pesquisa Estrategica em Saude (Grant PAPES 5-305674/2009-9), and the European Community's Seventh Framework Programme (FP7-2007-2013) under Grant HEALTH-F4-2011-281608. NR 56 TC 9 Z9 9 U1 0 U2 7 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 NOV 15 PY 2013 VL 191 IS 10 BP 5220 EP 5229 DI 10.4049/jimmunol.1203551 PG 10 WC Immunology SC Immunology GA 247AK UT WOS:000326584600035 PM 24133168 ER PT J AU Sherman, RE Li, J Shapley, S Robb, M Woodcock, J AF Sherman, Rachel E. Li, Jun Shapley, Stephanie Robb, Melissa Woodcock, Janet TI Expediting Drug Development - The FDA's New "Breakthrough Therapy" Designation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Sherman, Rachel E.; Li, Jun; Shapley, Stephanie; Robb, Melissa; Woodcock, Janet] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Sherman, RE (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 1 TC 43 Z9 47 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 NOV 14 PY 2013 VL 369 IS 20 BP 1877 EP 1880 DI 10.1056/NEJMp1311439 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 300MP UT WOS:000330468300005 PM 24224621 ER PT J AU Pinto, VB Burden, R Wagner, A Moran, EE Lee, CH AF Pinto, Valerian B. Burden, Robert Wagner, Allyn Moran, Elizabeth E. Lee, Che-Hung TI The Development of an Experimental Multiple Serogroups Vaccine for Neisseria meningitidis SO PLOS ONE LA English DT Article ID PNEUMOCOCCAL CONJUGATE VACCINE; SERUM BACTERICIDAL ACTIVITY; MEMBRANE VESICLE VACCINE; MENINGOCOCCAL MENINGITIS; GROUP-B; STRAINS; PROTEIN; POLYSACCHARIDES; EPIDEMIOLOGY; DETERMINANT AB A native outer membrane vesicles (NOMV) vaccine was developed from three antigenically diverse strains of Neisseria meningitidis that express the L1,8, L2, and L3,7 lipooligosaccharide (LOS) immunotypes, and whose synX, and lpxL1 genes were deleted.. Immunogenicity studies in mice showed that the vaccine induced bactericidal antibody against serogroups B, C, W, Y and X N. meningitidis strains. However, this experimental NOMV vaccine was not effective against serogroup A N. meningitidis strains. N. meningitidis capsular polysaccharide (PS) from serogroups A, C, W and Y were effective at inducing bactericidal antibody when conjugated to either tetanus toxoid or the fHbp1-fHbp2 fusion protein fHbp(1+2). The combination of the NOMV vaccine and the N. meningitidis serogroup A capsular polysaccharide (MAPS) protein conjugate was capable of inducing bactericidal antibodies against a limited number of N. meningitidis strains from serogroups A, B, C, W, Y and X tested in this study. C1 [Pinto, Valerian B.; Burden, Robert; Wagner, Allyn; Moran, Elizabeth E.] WRAIR, Div Bacterial & Rickettsial Dis, Silver Spring, MD USA. [Lee, Che-Hung] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Pinto, VB (reprint author), WRAIR, Div Bacterial & Rickettsial Dis, Silver Spring, MD USA. EM vpinto21@msn.com FU Military Infectious Disease Research Program FX This work was supported by the Military Infectious Disease Research Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 2 Z9 2 U1 1 U2 7 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 14 PY 2013 VL 8 IS 11 DI 10.1371/journal.pone.0079304 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 254DJ UT WOS:000327143800058 ER PT J AU Blomquist, TM Crawford, EL Lovett, JL Yeo, J Stanoszek, LM Levin, A Li, J Lu, M Shi, LM Muldrew, K Willey, JC AF Blomquist, Thomas M. Crawford, Erin L. Lovett, Jennie L. Yeo, Jiyoun Stanoszek, Lauren M. Levin, Albert Li, Jia Lu, Mei Shi, Leming Muldrew, Kenneth Willey, James C. TI Targeted RNA-Sequencing with Competitive Multiplex-PCR Amplicon Libraries SO PLOS ONE LA English DT Article ID POLYMERASE-CHAIN-REACTION; MESSENGER-RNA; EXPRESSION; SEQ; QUANTITATION; DNA; TRANSCRIPTS; TOOL AB Whole transcriptome RNA-sequencing is a powerful tool, but is costly and yields complex data sets that limit its utility in molecular diagnostic testing. A targeted quantitative RNA-sequencing method that is reproducible and reduces the number of sequencing reads required to measure transcripts over the full range of expression would be better suited to diagnostic testing. Toward this goal, we developed a competitive multiplex PCR-based amplicon sequencing library preparation method that a) targets only the sequences of interest and b) controls for inter-target variation in PCR amplification during library preparation by measuring each transcript native template relative to a known number of synthetic competitive template internal standard copies. To determine the utility of this method, we intentionally selected PCR conditions that would cause transcript amplification products (amplicons) to converge toward equimolar concentrations (normalization) during library preparation. We then tested whether this approach would enable accurate and reproducible quantification of each transcript across multiple library preparations, and at the same time reduce (through normalization) total sequencing reads required for quantification of transcript targets across a large range of expression. We demonstrate excellent reproducibility (R-2 = 0.997) with 97% accuracy to detect 2-fold change using External RNA Controls Consortium (ERCC) reference materials; high inter-day, inter-site and inter-library concordance (R-2 = 0.97-0.99) using FDA Sequencing Quality Control (SEQC) reference materials; and cross-platform concordance with both TaqMan qPCR (R-2 = 0.96) and whole transcriptome RNA-sequencing following "traditional'' library preparation using Illumina NGS kits (R-2 = 0.94). Using this method, sequencing reads required to accurately quantify more than 100 targeted transcripts expressed over a 10(7)-fold range was reduced more than 10,000-fold, from 2.3x10(9) to 1.4x10(5) sequencing reads. These studies demonstrate that the competitive multiplex-PCR amplicon library preparation method presented here provides the quality control, reproducibility, and reduced sequencing reads necessary for development and implementation of targeted quantitative RNA-sequencing biomarkers in molecular diagnostic testing. C1 [Blomquist, Thomas M.; Crawford, Erin L.; Yeo, Jiyoun; Stanoszek, Lauren M.; Willey, James C.] Univ Toledo, Dept Med, Toledo, OH 43606 USA. [Lovett, Jennie L.; Muldrew, Kenneth] Univ Toledo, Dept Pathol, Toledo, OH USA. [Levin, Albert; Li, Jia; Lu, Mei] Henry Ford Hlth Syst, Dept Publ Hlth Sci, Detroit, MI USA. [Shi, Leming] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Blomquist, TM (reprint author), Univ Toledo, Dept Med, Hlth Sci Campus, Toledo, OH 43606 USA. EM thomas.blomquist@utoledo.edu RI Lovett, Jennie/S-2996-2016 FU National Institutes of Health, National Cancer Institute [RC2-CA147652, IMAT R21-CA138397]; National Heart Lung and Blood Institute [RO1-HL108016]; University of Toledo Medical Center George Isaac Research Fund FX Significant portions of this study were paid for with funding provided by National Institutes of Health, National Cancer Institute (RC2-CA147652 and IMAT R21-CA138397) and National Heart Lung and Blood Institute (RO1-HL108016); and the University of Toledo Medical Center George Isaac Research Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 9 Z9 9 U1 1 U2 19 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 13 PY 2013 VL 8 IS 11 AR e79120 DI 10.1371/journal.pone.0079120 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255QK UT WOS:000327254700093 PM 24236095 ER PT J AU Yamazaki, A Liu, P Cheng, WC Badano, A AF Yamazaki, Asumi Liu, Peter Cheng, Wei-Chung Badano, Aldo TI Image Quality Characteristics of Handheld Display Devices for Medical Imaging SO PLOS ONE LA English DT Article ID RADIOLOGY; RESOLUTION; SYSTEMS; NOISE; IPAD; CT AB Handheld devices such as mobile phones and tablet computers have become widespread with thousands of available software applications. Recently, handhelds are being proposed as part of medical imaging solutions, especially in emergency medicine, where immediate consultation is required. However, handheld devices differ significantly from medical workstation displays in terms of display characteristics. Moreover, the characteristics vary significantly among device types. We investigate the image quality characteristics of various handheld devices with respect to luminance response, spatial resolution, spatial noise, and reflectance. We show that the luminance characteristics of the handheld displays are different from those of workstation displays complying with grayscale standard target response suggesting that luminance calibration might be needed. Our results also demonstrate that the spatial characteristics of handhelds can surpass those of medical workstation displays particularly for recent generation devices. While a 5 mega-pixel monochrome workstation display has horizontal and vertical modulation transfer factors of 0.52 and 0.47 at the Nyquist frequency, the handheld displays released after 2011 can have values higher than 0.63 at the respective Nyquist frequencies. The noise power spectra for workstation displays are higher than 1.2x10(-5) mm(2) at 1 mm(-1), while handheld displays have values lower than 3.7x10(-6) mm(2). Reflectance measurements on some of the handheld displays are consistent with measurements for workstation displays with, in some cases, low specular and diffuse reflectance coefficients. The variability of the characterization results among devices due to the different technological features indicates that image quality varies greatly among handheld display devices. C1 [Yamazaki, Asumi; Liu, Peter; Cheng, Wei-Chung; Badano, Aldo] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Yamazaki, Asumi] Nagoya Univ, Grad Sch Med Sci, Nagoya, Aichi 4648601, Japan. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. EM aldo.badano@fda.hhs.gov RI Cheng, Wei-Chung/E-6240-2014; OI badano, aldo/0000-0003-3712-6670 FU appointments to the Research Participation Program at the CDRH; Oak Ridge Institute for Science and Education FX AY and PL acknowledge funding by appointments to the Research Participation Program at the CDRH administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. DOE and the U.S. FDA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 21 TC 4 Z9 4 U1 0 U2 16 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 13 PY 2013 VL 8 IS 11 AR e79243 DI 10.1371/journal.pone.0079243 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255QK UT WOS:000327254700112 PM 24236113 ER PT J AU Lipiski, M Deuel, JW Baek, JH Engelsberger, WR Buehler, PW Schaer, DJ AF Lipiski, Miriam Deuel, Jeremy W. Baek, Jin Hyen Engelsberger, Wolfgang R. Buehler, Paul W. Schaer, Dominik J. TI Human Hp1-1 and Hp2-2 Phenotype-Specific Haptoglobin Therapeutics Are Both Effective In Vitro and in Guinea Pigs to Attenuate Hemoglobin Toxicity SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; SCAVENGER RECEPTOR; ATHEROSCLEROTIC PLAQUE; RAT CIRCULATION; HEME UPTAKE; GENOTYPE; IRON; OXIDATION; DISEASE; CD163 AB Aims: Infusion of purified haptoglobin (Hp) functions as an effective hemoglobin (Hb) scavenging therapeutic in animal models of hemolysis to prevent cardiovascular and renal injury. Epidemiologic studies demonstrate the phenotype heterogeneity of human Hp proteins and suggest differing vascular protective potential imparted by the dimeric Hp1-1 and the polymeric Hp2-2. Results:In vitro experiments and in vivo studies in guinea pigs were performed to evaluate phenotype-specific differences in Hp therapeutics. We found no differences between the two phenotypes in Hb binding and intravascular compartmentalization of Hb in vivo. Both Hp1-1 and Hp2-2 attenuate Hb-induced blood pressure response and renal iron deposition. These findings were consistent with equal prevention of Hb endothelial translocation. The modulation of oxidative Hb reactions by the two Hp phenotypes was not found to be different. Both phenotypes stabilize the ferryl (Fe4+) Hb transition state, provide heme retention within the complex, and prevent Hb-driven low-density lipoprotein (LDL) peroxidation. Hb-mediated peroxidation of LDL resulted in endothelial toxicity, which was equally blocked by the addition of Hp1-1 and Hp2-2. Innovation and Conclusion: The present data do not provide support for the concept that phenotype-specific Hp therapeutics offer differential efficacy in mitigating acute Hb toxicity. Antioxid. Redox Signal. 19, 1619-1633. C1 [Lipiski, Miriam; Deuel, Jeremy W.; Engelsberger, Wolfgang R.; Schaer, Dominik J.] Univ Zurich Hosp, Div Internal Med, CH-8091 Zurich, Switzerland. [Baek, Jin Hyen; Buehler, Paul W.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Schaer, DJ (reprint author), Univ Zurich Hosp, Div Internal Med, CH-8091 Zurich, Switzerland. EM paul.buehler@fda.hhs.gov; dominik.schaer@usz.ch FU Swiss National Science Foundation [310030/120658, 31003A/138500]; University of Zurich; Swiss Federal Commission for Technology and Innovation (CTI); FDA FX This work was supported by the Swiss National Science Foundation (grants 310030/120658 and 31003A/138500), the University of Zurich Research Priority Program "Integrative Human Physiology," the Swiss Federal Commission for Technology and Innovation (CTI), and FDA Internal Funding. The findings and conclusions in this article have not been formally disseminated by the FDA and should not be construed to represent any agency determination or policy. NR 43 TC 18 Z9 18 U1 0 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD NOV 10 PY 2013 VL 19 IS 14 BP 1619 EP 1633 DI 10.1089/ars.2012.5089 PG 15 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 239PF UT WOS:000326037100002 PM 23418677 ER PT J AU ElZarrad, MK Mukhopadhyay, P Mohan, N Hao, EK Dokmanovic, M Hirsch, DS Shen, Y Pacher, P Wu, WJ AF ElZarrad, M. Khair Mukhopadhyay, Partha Mohan, Nishant Hao, Enkui Dokmanovic, Milos Hirsch, Dianne S. Shen, Yi Pacher, Pal Wu, Wen Jin TI Trastuzumab Alters the Expression of Genes Essential for Cardiac Function and Induces Ultrastructural Changes of Cardiomyocytes in Mice SO PLOS ONE LA English DT Article ID CONGESTIVE-HEART-FAILURE; DILATED CARDIOMYOPATHY; BREAST-CANCER; INDUCED CARDIOTOXICITY; INDUCED APOPTOSIS; BLOOD-PRESSURE; VENTRICULAR MYOCYTES; CIRCADIAN VARIATION; TROPONIN-I; STRESS AB Treatment with trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of Human Epidermal Growth Factor Receptor 2 (HER2), very successfully improves outcomes for women with HER2-positive breast cancer. However, trastuzumab treatment was recently linked to potentially irreversible serious cardiotoxicity, the mechanisms of which are largely elusive. This study reports that trastuzumab significantly alters the expression of myocardial genes essential for DNA repair, cardiac and mitochondrial functions, which is associated with impaired left ventricular performance in mice coupled with significant ultrastructural alterations in cardiomyocytes revealed by electron microscopy. Furthermore, trastuzumab treatment also promotes oxidative stress and apoptosis in myocardium of mice, and elevates serum levels of cardiac troponin-I (cTnI) and cardiac myosin light chain-1 (cMLC1). The elevated serum levels of cMLC1 in mice treated with trastuzumab highlights the potential that cMLC1 could be a useful biomarker for trastuzumab-induced cardiotoxicity. C1 [ElZarrad, M. Khair; Mohan, Nishant; Dokmanovic, Milos; Hirsch, Dianne S.; Shen, Yi; Wu, Wen Jin] US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [ElZarrad, M. Khair] NCI, Interagcy Oncol Task Force IOTF Fellowship Progra, NIH, Bethesda, MD 20892 USA. [Mukhopadhyay, Partha; Hao, Enkui; Pacher, Pal] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA. RP Wu, WJ (reprint author), US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. EM wen.wu@fda.hhs.gov RI MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108 FU Federal Drug Administration-Office of Women's Health Research Science Program Award [750912CDR]; Interagency Oncology Task Force Joint Fellowship Program; United States Food and Drug Administration; National Cancer Institute FX This study is supported by Federal Drug Administration-Office of Women's Health Research Science Program Award to WJW (Project ID: 750912CDR) and the Interagency Oncology Task Force Joint Fellowship Program sponsored by the United States Food and Drug Administration and National Cancer Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 16 Z9 16 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 NOV 8 PY 2013 VL 8 IS 11 AR e79543 DI 10.1371/journal.pone.0079543 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255CG UT WOS:000327216200073 PM 24255707 ER PT J AU Bird, ST Delaney, JAC Brophy, JM Etminan, M Skeldon, SC Hartzema, AG AF Bird, Steven T. Delaney, Joseph A. C. Brophy, James M. Etminan, Mahyar Skeldon, Sean C. Hartzema, Abraham G. TI Tamsulosin treatment for benign prostatic hyperplasia and risk of severe hypotension in men aged 40-85 years in the United States: risk window analyses using between and within patient methodology SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID CONTROLLED CASE SERIES; URINARY-TRACT SYMPTOMS; BLOCKERS; SAFETY AB Objective To characterize risk of hypotension requiring admission to hospital in middle aged and older men treated with tamsulosin for benign prostatic hyperplasia. Design Population based retrospective cohort study (between patient methodology) and self controlled case series (within patient methodology). Setting Healthcare claims data from the IMS Lifelink database in the United States. Participants Men aged 40-85 years with private US healthcare insurance entering the cohort at their first dispensing for tamsulosin or for a 5a reductase inhibitor (5ARI) between January 2001 and June 2011 after a minimum of six months' enrolment. Main outcomes measures Hypotension requiring admission to hospital. Cox proportional hazards models estimated rate ratios at time varying intervals during follow-up: weeks 1-4, 5-8, and 9-12 after tamsulosin initiation; weeks 1-4, 5-8, and 9-12 after restarting tamsulosin (after a four week gap); and maintenance tamsulosin treatment (remaining exposed person time). Covariates included age, calendar year, demographics, antihypertensive use, healthcare use, and a Charlson comorbidity score. A self controlled case series, having implicit control for time invariant covariates, was additionally conducted. Results Among 383 567 new users of study drugs (tamsulosin 297 596; 5ARI 85 971), 2562 admissions to hospital for severe hypotension were identified. The incidence for hypotension was higher for tamsulosin (42.4 events per 10 000 person years) than for 5ARIs (31.3 events per 10 000 person years) or all accrued person time (29.1 events per 10 000 person years). After tamsulosin initiation, the cohort analysis identified an increased rate of hypotension during weeks 1-4 (rate ratio 2.12 (95% confidence interval 1.29 to 3.04)) and 5-8 (1.51 (1.04 to 2.18)), and no significant increase at weeks 9-12. The rate ratio for hypotension also increased at weeks 1-4 (1.84 (1.46 to 2.33)) and 5-8 (1.85 (1.45 to 2.36)) after restarting tamsulosin, as did maintenance tamsulosin treatment (1.19 (1.07 to 1.32)). The self controlled case series gave similar results as the cohort analysis. Conclusions We observed a temporal association between tamsulosin use for benign prostatic hyperplasia and severe hypotension during the first eight weeks after initiating treatment and the first eight weeks after restarting treatment. This association suggests that physicians should focus on improving counseling strategies to warn patients regarding the "first dose phenomenon" with tamsulosin. C1 [Bird, Steven T.] US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Dept Epidemiol, Silver Spring, MD USA. [Bird, Steven T.; Hartzema, Abraham G.] Univ Florida, Coll Pharm & Epidemiol Pharmaceut Outcomes & Poli, Gainesville, FL USA. [Delaney, Joseph A. C.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Brophy, James M.] McGill Univ, Royal Victoria Hosp, Ctr Hlth, Montreal, PQ H3A 1A1, Canada. [Etminan, Mahyar] Univ British Columbia, Fac Med, Therapeut Evaluat Unit, Prov Hlth Serv Author, Vancouver, BC V5Z 1M9, Canada. [Skeldon, Sean C.] Univ Toronto, Dept Surg, Div Urol, Toronto, ON, Canada. [Skeldon, Sean C.] Univ British Columbia, Dept Urol Sci, Vancouver, BC V5Z 1M9, Canada. RP Etminan, M (reprint author), Univ British Columbia, Fac Med, Therapeut Evaluat Unit, Prov Hlth Serv Author, Vancouver, BC V5Z 1M9, Canada. EM metminan@popi.ubc.ca FU McGill University Health Center; Fonds de la Recherche en Sante du Quebec; Ministere de la Sante et des Services Sociaux FX This work was funded in part by the McGill University Health Center, Fonds de la Recherche en Sante du Quebec, and the Ministere de la Sante et des Services Sociaux. The authors had full autonomy in the study design; the collection, analysis, and interpretation of data; the writing of the article; and the decision to submit it for publication. The authors have no other conflicts or competing interests to declare. Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure. pdf and declare: support from the McGill University Health Center, Fonds de la Recherche en Sante du Quebec, and the Ministere de la Sante et des Services Sociaux for the submitted work; JMB has received peer review financial support from le Fonds de la Recherche en Sante du Quebec, JACD has a research grant from the Agency for Healthcare Research and Quality, AGH is a principal investigator for the Observational Medical Outcomes Partnership, a private-public partnership designed to help improve drug safety monitoring, and STB is employed by the US Food and Drug Administration; no other relationships or activities that could appear to have influenced the submitted work. NR 29 TC 15 Z9 15 U1 1 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD NOV 5 PY 2013 VL 347 AR f6320 DI 10.1136/bmj.f6320 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 250XL UT WOS:000326890000002 PM 24192967 ER PT J AU Rashid, MM McKean, JW Kloke, JD AF Rashid, M. Mushfiqur McKean, Joseph W. Kloke, John D. TI REVIEW OF RANK-BASED PROCEDURES FOR MULTICENTER CLINICAL TRIALS SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Review DE Covariates; Mixed models; Nonparametric; Rank regression scores; Repeated measures; Robust; Variance components; Wilcoxon procedures ID LINEAR-MODELS; ROBUST ANALYSIS; MIXED MODELS; INFERENCES; REGRESSION AB This article reviews nonparametric alternatives to the mixed model normal theory analysis for the analyses of multicenter clinical trials. Under a mixed model, the traditional analysis is based on maximum likelihood theory under normal errors. This analysis, though, is not robust to outliers. Robust, rank-based, Wilcoxon-type procedures are reviewed for a multicenter clinical trial for the mixed model but without the assumption of normality. These procedures retain the high efficiency of Wilcoxon methods for simple location problems and are based on a fitting criterion which is robust to outliers in response space. A simple weighting scheme can be employed so that the procedures are robust to outliers in factor (design) space as well as response space. These rank-based analyses offer a complete analysis, including estimation of fixed effects and their standard errors, and tests of linear hypotheses. Both rank-based estimates of contrasts and individual treatment effects are reviewed. We illustrate the analyses using real data from a clinical trial. C1 [Rashid, M. Mushfiqur] US FDA, Silver Spring, MD USA. [McKean, Joseph W.] Western Michigan Univ, Kalamazoo, MI 49008 USA. [Kloke, John D.] Univ Wisconsin, Madison, WI USA. RP McKean, JW (reprint author), Western Michigan Univ, Dept Stat, Kalamazoo, MI 49008 USA. EM joseph.mckean@wmich.edu NR 21 TC 2 Z9 2 U1 0 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD NOV 2 PY 2013 VL 23 IS 6 BP 1207 EP 1227 DI 10.1080/10543406.2013.834919 PG 21 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 236HR UT WOS:000325786600001 PM 24138428 ER PT J AU Ross, HJ Hilton, T Puri, S Joshi, B Han, J Bhattacharya, B Moudgil, T Dubay, C Sanborn, RE Hu, HM Van De Ven, R Urba, W Aung, S Puri, R Fox, BA AF Ross, Helen J. Hilton, Traci Puri, Sachin Joshi, Bharat Han, Jing Bhattacharya, Bhaskar Moudgil, Tarsem Dubay, Christopher Sanborn, Rachel E. Hu, Hong-Ming Van De Ven, Reineke Urba, Walter Aung, Sandra Puri, Raj Fox, Bernard A. TI A NOVEL AUTOPHAGOSOME NON-SMALL CELL LUNG CANCER VACCINE (DRIBBLES) CONTAINS SHORT-LIVED PROTEINS, DEFECTIVE RIBOSOMAL PRODUCTS, AT LEAST NINE NCI-PRIORITIZED ANTIGENS, AND AGONISTS FOR TLR 2, 3, 4, 7, AND 9 SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Lung cancer vaccines; T-cell immune response; autophagosome; clinical trial C1 [Ross, Helen J.] Mayo Clin, Rochester, MN USA. [Hilton, Traci; Aung, Sandra] Ubivac, Portland, OR USA. [Puri, Sachin; Moudgil, Tarsem; Dubay, Christopher; Sanborn, Rachel E.; Hu, Hong-Ming; Van De Ven, Reineke; Urba, Walter; Fox, Bernard A.] Robert W Franz Canc Ctr, Earle A Chiles Res Inst, Portland, OR USA. [Joshi, Bharat; Han, Jing; Bhattacharya, Bhaskar; Puri, Raj] US FDA, Tumor Vaccine & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD NOV PY 2013 VL 8 SU 2 MA O08.01 BP S160 EP S160 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA AM1RE UT WOS:000339624900194 ER PT J AU Farel, CE Parker, SD Muessig, KE Grodensky, CA Jones, C Golin, CE Fogel, CI Wohl, DA AF Farel, Claire E. Parker, Sharon D. Muessig, Kathryn E. Grodensky, Catherine A. Jones, Chaunetta Golin, Carol E. Fogel, Catherine I. Wohl, David A. TI Sexuality, Sexual Practices, and HIV Risk Among Incarcerated African-American Women in North Carolina SO WOMENS HEALTH ISSUES LA English DT Article ID TRANSMITTED INFECTIONS; BEHAVIORS; IDENTITY; MEN; DISPARITIES; DETAINEES; JAIL AB Background: Women who have been in prison carry a greater lifetime risk of HIV for reasons that are not well understood. This effect is amplified in the Southeastern United States, where HIV incidence and prevalence is especially high among African-American (AA) women. The role of consensual sexual partnerships in the context of HIV risk, especially same-sex partnerships, merits further exploration. Methods: We conducted digitally recorded qualitative interviews with 29 AA women (15 HIV positive, 14 HIV negative) within 3 months after entry into the state prison system. We explored potential pre-incarceration HIV risk factors, including personal sexual practices. Two researchers thematically coded interview transcripts and a consensus committee reviewed coding. Results: Women reported complex sexual risk profiles during the 6 months before incarceration, including sex with women as well as prior sexual partnerships with both men and women. Condom use with primary male partners was low and a history of transactional sex work was prevalent. These behaviors were linked with substance use, particularly among HIV-positive women. Conclusions: Although women may not formally identify as bisexual or lesbian, sex with women was an important component of this cohort's sexuality. Addressing condom use, heterogeneity of sexual practices, and partner concurrency among at-risk women should be considered for reducing HIV acquisition and preventing forward transmission in women with a history of incarceration. Copyright (C) 2013 by the Jacobs Institute of Women's Health. Published by Elsevier Inc. C1 [Farel, Claire E.] Univ N Carolina, Sch Med, Inst Global Hlth & Infect Dis, Chapel Hill, NC 27599 USA. [Parker, Sharon D.] Brown Univ, Sch Med, Div Infect Dis, Providence, RI 02912 USA. [Parker, Sharon D.] Miriam Hosp, Providence, RI 02906 USA. [Muessig, Kathryn E.] Univ N Carolina, Dept Hlth Behav, Inst Global Hlth & Infect Dis, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA. [Grodensky, Catherine A.] Univ N Carolina, Social & Behav Sci Res Core, Ctr AIDS Res, Chapel Hill, NC 27599 USA. [Jones, Chaunetta] US FDA, Off Hlth Commun & Educ, Ctr Tobacco Prod, Rockville, MD 20857 USA. [Golin, Carol E.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Med, Dept Hlth Behav, Chapel Hill, NC 27599 USA. [Golin, Carol E.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Fogel, Catherine I.] Univ N Carolina, Sch Nursing, Chapel Hill, NC 27599 USA. [Wohl, David A.] Univ N Carolina, Inst Global Hlth & Infect Dis, HIV Serv North Carolina Dept Correct, Chapel Hill, NC 27599 USA. RP Farel, CE (reprint author), Univ N Carolina, Sch Med, Ctr Infect Dis, 130 Mason Farm Rd,CB 7030 2nd Floor Bioinformat, Chapel Hill, NC 27599 USA. EM cfarel@med.unc.edu FU NCATS NIH HHS [UL1TR000083, UL1 TR000083]; NIAID NIH HHS [P30 AI50410, P30 AI050410]; NICHD NIH HHS [K24 HD069204]; NIDA NIH HHS [F32 DA030268, F32 DA030268-01, T32 DA013911]; NIMH NIH HHS [R25 MH083620] NR 26 TC 1 Z9 1 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD NOV-DEC PY 2013 VL 23 IS 6 BP E357 EP E364 DI 10.1016/j.whi.2013.08.006 PG 8 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA AO1XY UT WOS:000341110100006 PM 24183410 ER PT J AU Miller, DL AF Miller, Donald L. TI EFFORTS TO OPTIMIZE RADIATION PROTECTION IN INTERVENTIONAL FLUOROSCOPY SO HEALTH PHYSICS LA English DT Article DE National Council on Radiation Protection and Measurements; fluoroscopy; medical radiation; radiation protection ID TRANSLUMINAL CORONARY ANGIOPLASTY; QUALITY IMPROVEMENT GUIDELINES; INDUCED SKIN INJURY; OF-THE-LITERATURE; CARDIAC-CATHETERIZATION; RADIOLOGY PROCEDURES; GUIDED PROCEDURES; PEDIATRIC-PATIENTS; ARTERY-STENOSIS; SAFETY PROGRAM AB While it has been known for more than a century that radiation presents risks to both the physician and the patient, skin injuries from fluoroscopy became increasingly rare after the 1930s, and radiation risk from fluoroscopy appeared to be adequately controlled. However, beginning in approximately 1975, new technologies and materials for interventional devices were developed. These enabled new procedures, and as these were instituted, skin injuries again occurred in patients. Four central issues were identified: equipment, quality management, operator training, and occupational radiation protection. Recognition that these were areas for improvement provoked changes in technology and practice that continue today. C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Miller, DL (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM donald.miller@fda.hhs.gov NR 110 TC 5 Z9 6 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD NOV PY 2013 VL 105 IS 5 BP 435 EP 444 DI 10.1097/HP.0b013e31829c355a PG 10 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 299BB UT WOS:000330368400007 PM 24077043 ER PT J AU Eichelberger, SL Sultana, I Gao, J Getie-Kebtie, M Alterman, M Eichelberger, MC AF Eichelberger, Schafer L. Sultana, Ishrat Gao, Jin Getie-Kebtie, Melkamu Alterman, Michail Eichelberger, Maryna C. TI Potency under pressure: the impact of hydrostatic pressure on antigenic properties of influenza virus hemagglutinin SO INFLUENZA AND OTHER RESPIRATORY VIRUSES LA English DT Article DE Hemagglutinin; hydrostatic pressure; immunogenicity; influenza; potency ID SINGLE-RADIAL-IMMUNODIFFUSION; IMMUNODEFICIENCY-VIRUS; SUBUNIT VACCINE; MEMBRANE-FUSION; INACTIVATION; ASSAY; NEURAMINIDASE; PROTECTION; INFECTION; ANTIBODY AB Background Influenza vaccines are effective in protecting against illness and death caused by this seasonal pathogen. The potency of influenza vaccines is measured by single radial immunodiffusion (SRID) assay that quantifies antigenic forms of hemagglutinin (HA). Hydrostatic pressure results in loss of binding of influenza virus to red blood cells, but it is not known whether this infers loss of potency. Objectives Our goal was to determine the impact of pressure on HA antigenic structure. Methods Viruses included in the 2010-2011 trivalent influenza vaccine were subjected to increasing number of cycles at 35 000 psi in a barocycler, and the impact of this treatment measured by determining hemagglutination units (HAU) and potency. Potency was assessed by SRID and immunogenicity in mice. Results After 25 cycles of pressure, the potency measured by SRID assay was below the limit of quantification for the H1N1 and B viruses used in our study, while the H3N2 component retained some potency that was lost after 50 pressure cycles. Pressure treatment also resulted in loss of HAU, but this did not strictly correlate with the potency value. Curiously, loss of potency was abrogated when influenza A, but not B, antigens were exposed to pressure in chicken egg allantoic fluid. Protection against pressure appeared to be mediated by specific interactions because addition of bovine serum albumin did not have the same effect. Conclusions Our results show that pressure-induced loss of potency is strain dependent and suggests that pressure treatment may be useful for identifying vaccine formulations that improve HA stability. C1 [Eichelberger, Schafer L.; Getie-Kebtie, Melkamu; Alterman, Michail] Off Cell Tissue & Gene Therapy, Div Cellular & Gene Therapies, Bethesda, MD USA. [Sultana, Ishrat; Gao, Jin; Eichelberger, Maryna C.] US FDA, Div Viral Prod, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Eichelberger, MC (reprint author), US FDA, Div Viral Prod, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM maryna.eichelberger@fda.hhs.gov FU Pandemic Influenza funds FX We thank CBER's animal care managers and staff for excellent animal husbandry, Vladimir Lugovtsev and Ewan Plant for helpful suggestions during the preparation of this manuscript. This study was supported by Pandemic Influenza funds. SLE and IS were supported by training funds administered by the Oak Ridge Institute for Science and Education. NR 33 TC 1 Z9 1 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1750-2640 EI 1750-2659 J9 INFLUENZA OTHER RESP JI Influenza Other Respir. Viruses PD NOV PY 2013 VL 7 IS 6 BP 961 EP 968 DI 10.1111/irv.12102 PG 8 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA AA3OG UT WOS:000331001400013 PM 23496824 ER PT J AU Nielsen, LH Gordon, S Holm, R Selen, A Rades, T Mullertz, A AF Nielsen, Line Hagner Gordon, Sarah Holm, Rene Selen, Arzu Rades, Thomas Mullertz, Anette TI Preparation of an amorphous sodium furosemide salt improves solubility and dissolution rate and leads to a faster T-max after oral dosing to rats SO EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS LA English DT Article DE Poorly soluble drugs; Amorphous salt; Furosemide; Biorelevant dissolution; Solubility; Oral bioavailability ID WATER-SOLUBLE DRUGS; HUMAN INTESTINAL FLUIDS; PHYSICOCHEMICAL CHARACTERIZATION; GASTROINTESTINAL-TRACT; PHARMACEUTICAL SYSTEMS; SOLID DISPERSION; MELT EXTRUSION; STABILITY; BIOAVAILABILITY; INDOMETHACIN AB Amorphous forms of furosemide sodium salt and furosemide free acid were prepared by spray drying. For the preparation of the amorphous free acid, methanol. was utilised as the solvent, whereas the amorphous sodium salt was formed from a sodium hydroxide-containing aqueous solvent in equimolar amounts of NaOH and furosemide. Information about the structural differences between the two amorphous forms was obtained by Fourier Transform Infrared Spectroscopy (FTIR), and glass transition temperature (T-g) was determined using Differential Scanning Calorimetry (DSC). The stability and devitrification tendency of the two amorphous forms were investigated by X-ray Powder Diffraction (XRPD). The apparent solubility of the two amorphous forms and the crystalline free acid form of furosemide in various gastric and intestinal stimulated media was determined. Moreover, the dissolution characteristics of the two amorphous forms and of crystalline free acid were investigated. FTIR confirmed molecular differences between the amorphous free acid and salt. The amorphous salt showed a T-g of 101.2 degrees C, whereas the T-g for the amorphous free acid was found to be 61.8 degrees C. The amorphous free acid was physically stable for 4 days at 22 degrees C and 33% relative humidity (RH), while the amorphous salt exhibited physical stability for 291 days at the same storage conditions. When storing the amorphous forms at 40 degrees C and 75% RH both forms converted to crystalline forms after 2 days. The apparent solubility of the amorphous salt form was higher than that of both amorphous and crystalline free acid in all media studied. All three forms of furosemide exhibited a greater solubility in the presence of biorelevant media as compared to buffer, however, an overall trend for a further increase in solubility in relation to an increase in media surfactant concentration was not seen. The amorphous salt demonstrated an 8- and 20-fold higher intrinsic dissolution rate (IDR) when compared to amorphous and crystalline free acid, respectively. The promising properties of the amorphous salt in vitro were further evaluated in an in vivo study, where solid dosage forms of the amorphous salt, amorphous and crystalline free acid and a solution of furosemide were administered orally to rats. The amorphous salt exhibited a significantly faster T-max compared to the solution and amorphous and crystalline free acid. C-max for the solution was significantly higher compared to the three furosemide forms. No significant difference was found in AUC and absolute bioavailability for the solution, crystalline free acid and the two amorphous forms of furosemide. It can be concluded that the higher IDR and higher apparent solubility of the amorphous salt resulted in a faster T-max compared to the amorphous and crystalline free acid. Published by Elsevier B.V. C1 [Nielsen, Line Hagner; Gordon, Sarah; Holm, Rene; Rades, Thomas; Mullertz, Anette] Univ Copenhagen, Dept Pharm, Fac Hlth & Med Sci, DK-2100 Copenhagen, Denmark. [Holm, Rene] H Lundbeck & Co AS, Biol & Pharmaceut Sci, Valby, Denmark. [Selen, Arzu] US FDA, Silver Spring, MD USA. [Mullertz, Anette] Univ Copenhagen, Dept Pharm, Fac Hlth & Med Sci, Bioneer FARMA, DK-2100 Copenhagen, Denmark. RP Mullertz, A (reprint author), Univ Copenhagen, Dept Pharm, Fac Hlth & Med Sci, Bioneer FARMA, Univ Pk 2, DK-2100 Copenhagen, Denmark. EM anette.mullertz@sund.ku.dk RI Hagner Nielsen, Line/C-7312-2014; OI Hagner Nielsen, Line/0000-0002-3789-4816; Rades, Thomas/0000-0002-7521-6020; Mullertz, Anette/0000-0003-3020-8892 FU Villum Kann Rasmussen Foundation FX The authors would like to acknowledge the Villum Kann Rasmussen Foundation for financial support in form of NAnoMEChanical sensors and actuators, fundamentals and new directions (NAMEC) - a VKR Centre of Excellence. Martin Lau Christiansen (Department of Pharmacy, University of Copenhagen) is acknowledged for assistance with the pharmacokinetic analysis and Richard T. Lostritto (US Food and Drug Administration) for assistance with the manuscript. Furthermore, the personnel in the animal facilities at H. Lundbeck A/S are acknowledged for their skilful handling of the rats. Part of the work presented in this paper is the result of a collaborative project, carried out in partnership between the University of Copenhagen, the Institute of Pharmaceutical Technology, Goethe University, Frankfurt and the US Food and Drug Administration. NR 45 TC 18 Z9 18 U1 3 U2 60 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0939-6411 EI 1873-3441 J9 EUR J PHARM BIOPHARM JI Eur. J. Pharm. Biopharm. PD NOV PY 2013 VL 85 IS 3 BP 942 EP 951 DI 10.1016/j.ejpb.2013.09.002 PN B PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 296QP UT WOS:000330200800014 PM 24075980 ER PT J AU Rahman, Z Siddiqui, A Khan, MA AF Rahman, Ziyaur Siddiqui, Akhtar Khan, Mansoor A. TI Orally disintegrating tablet of novel salt of antiepileptic drug: Formulation strategy and evaluation SO EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS LA English DT Article DE Lamotrigine-cyclamate salt; Orally disintegrating tablet; Disintegration time; Electronic tongue; Near infrared chemical imaging; Dissolution ID ELECTRONIC TONGUE; TANNATE COMPLEXES; COATED TABLETS; ADHERENCE; MEDICATION AB The aim of present research was to design and evaluate orally disintegrating tablet (ODT) of novel lamotrigine-cyclamate salt. Box-Behnken response surface methodology was selected to design the optimized formulation. The independent factors selected were tablet hardness (X-1), disintegrant (X-2) and lubricant (X-3) levels, and responses chosen were disintegration time (DT, Y-1), friability (Y-2), T-50 (Y-3), and T-90 (Y-4). The tablets were also characterized for drug uniformity by near infrared chemical imaging (NIR-CI) and taste masking evaluation by electronic tongue. All the selected independent variables were statistically (p < 0.05) effect the Y-1 while Y-2, Y-3, and Y-4 affected only by X-2. The optimized ODT was found to meet the regulatory requirement of DT and friability specification. The NIR-CI images indicated uniform distribution of active and inactive ingredients within the tablets. The electronic tongue results were analyzed by principle component analysis (PCA). It indicated that novel salt of lamotrigine and its ODT formulation have a taste similar to cyclamic acid which is indicated by close proximity on PCA score plot, lower Euclidean distance, and high discrimination index values. Furthermore, these parameters were very close to ODT placebo formulation. On the other hand, lamotrigine, its ODT, and placebo formulation were far from each other. In summary, lamotrigine salt provides another avenue for pediatric friendly formulation for children and will enhance patience compliance. Published by Elsevier B.V. C1 [Rahman, Ziyaur; Siddiqui, Akhtar; Khan, Mansoor A.] US FDA, Div Prod Qual & Res, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Khan, MA (reprint author), 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 FDA-NIH interagency agreement; MCMi infrastructure support grant; Oak Ridge Institute for Science and Education (ORISE) FX This research was supported in part by FDA-NIH interagency agreement and also by the MCMi infrastructure support grant. The authors would also like to thank the Oak Ridge Institute for Science and Education (ORISE) for supporting the post-doctoral research. NR 41 TC 8 Z9 11 U1 2 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0939-6411 EI 1873-3441 J9 EUR J PHARM BIOPHARM JI Eur. J. Pharm. Biopharm. PD NOV PY 2013 VL 85 IS 3 BP 1300 EP 1309 DI 10.1016/j.ejpb.2013.06.006 PN B PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 296QP UT WOS:000330200800055 PM 23800704 ER PT J AU Munoz, MA Liu, W Delaney, JAC Brown, E Mugavero, MJ Mathews, WC Napravnik, S Willig, JH Eron, JJ Hunt, PW Kahn, JO Saag, MS Kitahata, MM Crane, HM AF Munoz, Monica A. Liu, Wei Delaney, Joseph A. C. Brown, Elizabeth Mugavero, Michael J. Mathews, W. Chris Napravnik, Sonia Willig, James H. Eron, Joseph J. Hunt, Peter W. Kahn, James O. Saag, Michael S. Kitahata, Mari M. Crane, Heidi M. TI Comparative Effectiveness of Fish Oil Versus Fenofibrate, Gemfibrozil, and Atorvastatin on Lowering Triglyceride Levels Among HIV-Infected Patients in Routine Clinical Care SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 27th International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 16, 2011 CL Chicago, IL DE fish oil; triglycerides; dyslipidemia; fibrates; HIV ID CORONARY-HEART-DISEASE; N-3 FATTY-ACIDS; ANTIRETROVIRAL THERAPY; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; ETHYL-ESTERS; RISK-FACTORS; DIETARY; HYPERTRIGLYCERIDEMIA; TRIAL AB Objective: The goal of this study was to compare the effectiveness of fish oil, fenofibrate, gemfibrozil, and atorvastatin on reducing triglyceride (TG) levels among a large cohort of HIV-infected patients in clinical care. Design: Retrospective observational cohort study. Methods: The primary endpoint was absolute change in TG levels measured using the last TG value pretreatment and the first TG value posttreatment. A pre-post quasi-experimental design was used to estimate the change in TG because of initiating fish oil. Linear regression models examined the comparative effectiveness of treatment with fish oil versus gemfibrozil, fenofibrate, or atorvastatin for TG reduction. Models were adjusted for baseline differences in age, sex, race, CD4(+) cell count, diabetes, body mass index, protease inhibitor use, and time between TG measures. Results: A total of 493 patients (mean age, 46 years; 95% male) were included (46 patients receiving gemfibrozil; 80, fenofibrate; 291, atorvastatin; and 76, fish oil) with a mean baseline TG of 347 mg/dL. New use of fish oil decreased TG [Delta TG, -45 mg/dL; 95% confidence interval (CI): -80 to -11] in the pre-post study. Compared with fish oil (reference), fibrates were more effective (Delta TG, -66; 95% CI: -120 to -12) in reducing TG levels, whereas atorvastatin was not (Delta TG, -39; 95% CI: -86 to 9). Conclusions: In HIV-infected patients in routine clinical care, fish oil is less effective than fibrates (but not atorvastatin) at lowering TG values. Fish oil may still represent an attractive alternative for patients with moderately elevated TGs, particularly among patients who may not want or tolerate fibrates. C1 [Munoz, Monica A.; Liu, Wei; Delaney, Joseph A. C.] Univ Florida, Dept Pharmaceut Outcome & Policy, Gainesville, FL USA. [Munoz, Monica A.] US FDA, Silver Spring, MD USA. [Kitahata, Mari M.; Crane, Heidi M.] Univ Washington, Dept Med, Seattle, WA 98106 USA. [Brown, Elizabeth] Univ Washington, Dept Biostat, Seattle, WA 98106 USA. [Mugavero, Michael J.; Willig, James H.; Saag, Michael S.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Mathews, W. Chris] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Napravnik, Sonia; Eron, Joseph J.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Hunt, Peter W.; Kahn, James O.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Crane, HM (reprint author), Univ Washington, Harborview Med Ctr, 325 9th Ave,Box 359931, Seattle, WA 98106 USA. EM hcrane@uw.edu RI Mathews, William/E-4451-2010 OI Mathews, William/0000-0002-2352-0725 FU AHRQ HHS [R21 HS019516, R21HS019516]; NIAID NIH HHS [P30AI027757, R24 AI067039, R24AI067039, P30 AI027757, P30 AI050410] NR 36 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2013 VL 64 IS 3 BP 254 EP 260 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 300GY UT WOS:000330453600005 PM 23892238 ER PT J AU Zhang, G Brown, EW Hammack, TS AF Zhang, G. Brown, E. W. Hammack, T. S. TI Comparison of different preenrichment broths, egg:preenrichment broth ratios, and surface disinfection for the detection of Salmonella enterica ssp enterica serovar Enteritidis in shell eggs SO POULTRY SCIENCE LA English DT Article DE Salmonella; detection; enrichment; broth; egg ID RAPID DETECTION; UNITED-STATES; LAYING HENS; ENRICHMENT; POULTRY; GROWTH; POOLS; SPP.; MEAT AB Salmonella enterica ssp. enterica serovar Enteritidis is the leading reported cause of Salmonella infections. Most Salmonella Enteritidis infections are associated with whole shell eggs and egg products. This project attempted to lay the foundation for improving the Food and Drug Administration's current Bacteriological Analytical Manual method for the detection of Salmonella Enteritidis in shell eggs. Two Salmonella Enteritidis isolates were used for comparisons among different preenrichment and enrichment media and for the evaluation of egg: preenrichment broth ratios for the detection of Salmonella Enteritidis in shell eggs. The effect of surface disinfection on the detection of Salmonella Enteritidis in shell eggs was also investigated. The results indicated that tryptic soy broth (TSB) was similar to TSB plus ferrous sulfate, but significantly (alpha = 0.05) better than nutrient broth, Universal Preenrichment broth, and buffered peptone water when used for preenrichment of Salmonella in shell eggs. Salmonella Enteritidis populations after enrichment with Rappaport-Vassiliadis broth were 0.40 to 1.11 log cfu/mL of culture lower than those in preenrichment cultures. The reduction was statistically significant (alpha = 0.05). Egg: broth ratios at 1:9 and 1:2 produced significantly (alpha = 0.05) higher Salmonella Enteritidis populations after preenrichment with TSB with inoculum levels at 4 cfu/100 g of eggs and 40 cfu/1,000 g of eggs than the ratio at 1:1. Salmonella Enteritidis populations in TSB preenrichment cultures of shell eggs surface-disinfected with 70% alcohol: iodine/potassium iodide solution and untreated control were 9.11 +/- 0.11 and 9.18 +/- 0.05 log cfu/mL, respectively, for SE 13-2, and 9.20 +/- 0.04 and 9.16 +/- 0.05 log cfu/mL, respectively, for SE CDC_2010K_1543. Surface disinfection of eggs did not reduce the sensitivity of detection of Salmonella Enteritidis in liquid eggs. These results could improve the Food and Drug Administration's current Bacteriological Analytical Manual method for the detection of Salmonella in shell eggs by simplifying the preenrichment medium and changing the sample handling before enrichment. C1 [Zhang, G.; Brown, E. W.; Hammack, T. S.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Zhang, G (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Guodong.Zhang@fda.hhs.gov NR 24 TC 0 Z9 0 U1 4 U2 12 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874-9604 USA SN 0032-5791 EI 1525-3171 J9 POULTRY SCI JI Poult. Sci. PD NOV PY 2013 VL 92 IS 11 BP 3010 EP 3016 DI 10.3382/ps.2013-03022 PG 7 WC Agriculture, Dairy & Animal Science SC Agriculture GA 301IE UT WOS:000330525200024 PM 24135606 ER PT J AU Betts, KR Hinsz, VB AF Betts, Kevin R. Hinsz, Verlin B. TI Strong shared representations promote schema-consistent memory errors in groups SO GROUP PROCESSES & INTERGROUP RELATIONS LA English DT Article DE cognitive representations; error correction; groups; memory errors; shared representations ID RECOGNITION MEMORY; FALSE MEMORIES; COLLABORATION; INFORMATION; RECALL; INDIVIDUALS; PERFORMANCE; INHIBITION; PREDICTION; JUDGMENTS AB We created the conditions necessary for cognitive representations to develop by presenting individuals and groups with word lists consisting of items high and low in associative strength. Strong cognitive representations were found to promote more schema-consistent memory errors than weaker representations. Moreover, strong cognitive representations resulted in more of these errors for groups than individuals. Weak cognitive representations, in contrast, resulted in fewer of these errors for groups than individuals. We find that variation in the frequency of memory errors between individuals and groups is influenced by the strength of shared representations that interfere with the ability of groups to correct schema-consistent memory errors among their members. Further analyses suggest that strong shared representations also aid correct recall relative to weak shared representations. We conclude that despite general advantages of collaboration, select circumstances that allow for strong shared representations may promote schema-consistent memory errors in groups. C1 [Betts, Kevin R.] US FDA, Silver Spring, MD 20993 USA. [Hinsz, Verlin B.] N Dakota State Univ, Fargo, ND USA. RP Betts, KR (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Kevin.Betts@fda.hhs.gov NR 43 TC 3 Z9 3 U1 4 U2 10 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1368-4302 EI 1461-7188 J9 GROUP PROCESS INTERG JI Group Process Intergroup Relat. PD NOV PY 2013 VL 16 IS 6 BP 734 EP 751 DI 10.1177/1368430213486206 PG 18 WC Psychology, Social SC Psychology GA 298IJ UT WOS:000330317100006 ER EF