FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Wu, J Patmore, DM Jousma, E Eaves, DW Breving, K Patel, AV Schwartz, EB Fuchs, JR Cripe, TP Stemmer-Rachamimov, AO Ratner, N AF Wu, J. Patmore, D. M. Jousma, E. Eaves, D. W. Breving, K. Patel, A. V. Schwartz, E. B. Fuchs, J. R. Cripe, T. P. Stemmer-Rachamimov, A. O. Ratner, N. TI EGFR-STAT3 signaling promotes formation of malignant peripheral nerve sheath tumors SO ONCOGENE LA English DT Article DE EGFR; STAT3; sarcoma; MPNST; NF1 ID GROWTH-FACTOR RECEPTOR; BREAST-CANCER CELLS; NEUROFIBROMATOSIS TYPE-1; TYROSINE KINASE; SCHWANN-CELLS; SELF-RENEWAL; MOUSE MODELS; STEM-CELLS; NF1; STAT3 AB Malignant peripheral nerve sheath tumors (MPNSTs) develop sporadically or in the context of neurofibromatosis type 1. Epidermal growth factor receptor (EGFR) overexpression has been implicated in MPNST formation, but its precise role and relevant signaling pathways remain unknown. We found that EGFR overexpression promotes mouse neurofibroma transformation to aggressive MPNST (GEM-PNST). Immunohistochemistry demonstrated phosphorylated STAT3 (Tyr705) in both human MPNST and mouse GEM-PNST. A specific JAK2/STAT3 inhibitor FLLL32 delayed MPNST formation in an MPNST xenograft nude mouse model. STAT3 knockdown by shRNA prevented MPNST formation in vivo. Finally, reducing EGFR activity strongly reduced pSTAT3 in vivo. Thus, an EGFR-STAT3 pathway is necessary for MPNST transformation and establishment of MPNST xenografts growth but not for tumor maintenance. Efficacy of the FLLL32 pharmacological inhibitor in delaying MPNST growth suggests that combination therapies targeting JAK/STAT3 might be useful therapeutics. C1 [Wu, J.; Patmore, D. M.; Jousma, E.; Eaves, D. W.; Breving, K.; Patel, A. V.; Cripe, T. P.; Ratner, N.] Cincinnati Childrens Hosp Med Ctr, Cincinnati Childrens Hosp Res Fdn, Canc & Blood Dis Inst, Cincinnati, OH 45229 USA. [Schwartz, E. B.; Fuchs, J. R.] Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA. [Stemmer-Rachamimov, A. O.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Stemmer-Rachamimov, A. O.] Harvard Univ, Sch Med, Boston, MA USA. RP Ratner, N (reprint author), Cincinnati Childrens Hosp, Dept Pediat, Div Exp Hematol & Canc Biol, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM nancy.ratner@cchmc.org FU National Institutes of Health [R01 NS28840, P50 NS057531]; Department of Defense New Investigator Award [NF100053]; Ohio State University Comprehensive Cancer Center Pelotonia Idea Grant; American Cancer Society [IRG-67-003-44] FX We thank Dr Andre Bernards (Massachusetts General Hospital) and Drs Jiayuh Lin, Pui-Kai Li and Gregory B Lesinski (Ohio State University) for helpful discussions. This work was supported by the National Institutes of Health (R01 NS28840 and P50 NS057531 to NR), and Department of Defense New Investigator Award (NF100053) and an Ohio State University Comprehensive Cancer Center Pelotonia Idea Grant (to JW). The American Cancer Society (IRG-67-003-44) supported JRF. NR 42 TC 22 Z9 22 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD JAN 9 PY 2014 VL 33 IS 2 BP 173 EP 180 DI 10.1038/onc.2012.579 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 286BY UT WOS:000329440700005 PM 23318430 ER PT J AU Minnerup, J Wagner, DC Strecker, JK Posel, C Sevimli-Abdis, S Schmidt, A Schilling, M Boltze, J Diederich, K Schabitz, WR AF Minnerup, Jens Wagner, Daniel-Christoph Strecker, Jan-Kolja Poesel, Claudia Sevimli-Abdis, Sevgi Schmidt, Antje Schilling, Matthias Boltze, Johannes Diederich, Kai Schaebitz, Wolf-Ruediger TI Bone marrow-derived mononuclear cells do not exert acute neuroprotection after stroke in spontaneously hypertensive rats SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Article DE bone marrow-derived mononuclear cells; middle cerebral artery occlusion; stroke; dose-response; spontaneously hypertensive rats ID ACUTE ISCHEMIC-STROKE; CEREBRAL-ARTERY OCCLUSION; COLONY-STIMULATING FACTOR; STEM-CELLS; BRAIN PROTECTION; TRANSPLANTATION; RECOVERY; THERAPY; INJURY; YOUNG AB Bone marrow-derived mononuclear cells (BM-MNCs) were shown to improve the outcome in animal stroke models and clinical pilot studies on BM-MNCs for stroke patients were already conducted. However, relevant aspects of pre-clinical evaluation, such as the use of animals with comorbidities and dose response studies, were not thoroughly addressed so far. We therefore investigated different BM-MNC doses in the clinical meaningful stroke model of spontaneously hypertensive (SH) rats. Three hours after the onset of transient middle cerebral artery occlusion (MCAO) animals received either one of three syngeneic BM-MNC doses or placebo intravenously. The primary endpoint was the infarct size. Secondary endpoints included functional outcome, mortality, inflammatory processes, and the dose-response relationship. In contrast to previous studies which used healthy animals no beneficial effect of BM-MNCs was found. Infarct volumes, mortality, behavioral outcomes, and the extent of the inflammatory response to cerebral ischemia were comparable in all groups. In conclusion, we could not demonstrate that early BM-MNC treatment improves the outcome after stroke in SH rats. Whether BM-MNCs improve neurological recovery after delayed treatment initiation was not investigated in the present study, but our data indicates that this should be determined in co-morbid animal stroke models before moving to large-scale clinical studies. Future preclinical stroke studies on co-morbid animals should also include groups of healthy animals in order to determine whether negative results can be attributed to the comorbid condition. C1 [Minnerup, Jens; Strecker, Jan-Kolja; Sevimli-Abdis, Sevgi; Schmidt, Antje; Schilling, Matthias; Diederich, Kai] Univ Munster, Dept Neurol, Neurol Klin, D-48149 Munster, Germany. [Wagner, Daniel-Christoph; Poesel, Claudia; Boltze, Johannes] Univ Leipzig, Fraunhofer Inst Cell Therapy & Immunol, D-04109 Leipzig, Germany. [Wagner, Daniel-Christoph; Poesel, Claudia; Boltze, Johannes] Univ Leipzig, Translat Ctr Regenerat Med, D-04109 Leipzig, Germany. [Sevimli-Abdis, Sevgi] CATO Europe GmbH, Cologne, Germany. [Boltze, Johannes] Massachusetts Gen Hosp, Charlestown, MA USA. [Boltze, Johannes] Harvard Univ, Sch Med, Charlestown, MA USA. [Schaebitz, Wolf-Ruediger] EVK Bielefeld, Neurol Klin, Bielefeld, Germany. RP Minnerup, J (reprint author), Univ Munster, Dept Neurol, Neurol Klin, Albert Schweitzer Campus 1, D-48149 Munster, Germany. EM minnerup@uni-muenster.de FU Bundesministerium fur Bildung und Forschung (BMBF) [01GN0980, 50810545]; Else Kroner-Fresenius-Stiftung [2010_A64] FX The authors gratefully acknowledge the excellent technical assistance of Birgit Geng and Maike Hoppen. This study was supported by grants of the Bundesministerium fur Bildung und Forschung (BMBF, Project MARS, 01GN0980 and BMBF, Project SIRIUS, 50810545) and the Else Kroner-Fresenius-Stiftung (2010_A64). NR 32 TC 7 Z9 7 U1 1 U2 3 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5102 J9 FRONT CELL NEUROSCI JI Front. Cell. Neurosci. PD JAN 8 PY 2014 VL 7 AR 288 DI 10.3389/fncel.2013.00288 PG 9 WC Neurosciences SC Neurosciences & Neurology GA AA4EY UT WOS:000331049400002 PM 24409120 ER PT J AU Gettings, J O'Neill, B Chokshi, DA Colbert, JA Gill, P Lebovic, G Lexchin, J Persaud, N AF Gettings, Jennifer O'Neill, Braden Chokshi, Dave A. Colbert, James A. Gill, Peter Lebovic, Gerald Lexchin, Joel Persaud, Navindra TI Differences in the Volume of Pharmaceutical Advertisements between Print General Medical Journals SO PLOS ONE LA English DT Article ID REFERENCES; QUALITY; YES AB Background: Pharmaceutical advertisements have been argued to provide revenue that medical journals require but they are intended to alter prescribing behaviour and they are known to include low quality information. We determined whether a difference exists in the current level of pharmaceutical advertising in print general medical journals, and we estimated the revenue generated from print pharmaceutical advertising. Methods: Six print general medical journals in Canada, the United States, and the United Kingdom were sampled between 2007 and 2012. The number of advertisements and other journal content in selected issues of the Canadian Medical Association Journal (CMAJ), Canadian Family Physician (CFP), Journal of the American Medical Association (JAMA), New England Journal of Medicine (NEJM), British Medical Journal (BMJ), and Lancet were determined. Revenue gained from pharmaceutical advertising was estimated using each journal's 2013 advertising price list. Findings: The two Canadian journals sampled (CMAJ, CFP) contained five times more advertisements than the two American journals (JAMA, NEJM), and two British journals (BMJ, Lancet) (p<0.0001). The estimated annual revenue from pharmaceutical advertisements ranged from 0.025 pound million (for Lancet) to 3.8 pound million (for JAMA). The cost savings due to revenue from pharmaceutical advertising to each individual subscriber ranged from 0.02 pound (for Lancet) to 3.56 pound (for CFP) per issue. Conclusion: The volume of pharmaceutical advertisements differs between general medical journals, with the two Canadian journals sampled containing the most advertisements. International and temporal variations suggest that there is an opportunity for all general medical journals to reduce the number of pharmaceutical advertisements, explore other sources of revenue, and increase transparency regarding sources of revenue. C1 [Gettings, Jennifer; Persaud, Navindra] St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada. [O'Neill, Braden; Gill, Peter] Univ Oxford, Dept Primary Care Hlth Sci, Oxford, England. [O'Neill, Braden] Univ Calgary, Fac Med, Calgary, AB, Canada. [Chokshi, Dave A.] US Dept Vet Affairs, Washington, DC USA. [Colbert, James A.] Brigham & Womens Hosp, Div Med Commun, Boston, MA 02115 USA. [Colbert, James A.] Newton Wellesley Hosp, Dept Med, Boston, MA USA. [Gill, Peter] Univ Alberta, Fac Med & Dent, Edmonton, AB, Canada. [Lebovic, Gerald] St Michaels Hosp, Appl Hlth Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada. [Lebovic, Gerald] Univ Toronto, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Lexchin, Joel] York Univ, Sch Hlth Policy & Management, Toronto, ON M3J 2R7, Canada. [Lexchin, Joel] Univ Hlth Network, Emergency Dept, Toronto, ON, Canada. [Lexchin, Joel; Persaud, Navindra] Univ Toronto, Dept Family & Community Med, Toronto, ON M5S 1A1, Canada. [Persaud, Navindra] St Michaels Hosp, Dept Family & Community Med, Toronto, ON M5B 1W8, Canada. RP Persaud, N (reprint author), St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, 30 Bond St, Toronto, ON M5B 1W8, Canada. EM nav.persaud@utoronto.ca OI Chokshi, Dave/0000-0001-7467-4591 NR 20 TC 1 Z9 1 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 8 PY 2014 VL 9 IS 1 AR e84790 DI 10.1371/journal.pone.0084790 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 291WL UT WOS:000329862500169 PM 24416286 ER PT J AU Sargoy, A Sun, XP Barnes, S Brecha, NC AF Sargoy, Allison Sun, Xiaoping Barnes, Steven Brecha, Nicholas C. TI Differential Calcium Signaling Mediated by Voltage-Gated Calcium Channels in Rat Retinal Ganglion Cells and Their Unmyelinated Axons SO PLOS ONE LA English DT Article ID DISPLACED AMACRINE CELLS; BIPOLAR CELLS; MOUSE RETINA; OPTIC-NERVE; BETA-SUBUNITS; IN-VIVO; CURRENTS; NEURONS; MIBEFRADIL; EXPRESSION AB Aberrant calcium regulation has been implicated as a causative factor in the degeneration of retinal ganglion cells (RGCs) in numerous injury models of optic neuropathy. Since calcium has dual roles in maintaining homeostasis and triggering apoptotic pathways in healthy and injured cells, respectively, investigation of voltage-gated Ca channel (VGCC) regulation as a potential strategy to reduce the loss of RGCs is warranted. The accessibility and structure of the retina provide advantages for the investigation of the mechanisms of calcium signalling in both the somata of ganglion cells as well as their unmyelinated axons. The goal of the present study was to determine the distribution of VGCC subtypes in the cell bodies and axons of ganglion cells in the normal retina and to define their contribution to calcium signals in these cellular compartments. We report L-type Ca channel alpha 1C and alpha 1D subunit immunoreactivity in rat RGC somata and axons. The N-type Ca channel alpha 1B subunit was in RGC somata and axons, while the P/Q-type Ca channel alpha 1A subunit was only in the RGC somata. We patch clamped isolated ganglion cells and biophysically identified T-type Ca channels. Calcium imaging studies of RGCs in wholemounted retinas showed that selective Ca channel antagonists reduced depolarization-evoked calcium signals mediated by L-, N-, P/Q- and T-type Ca channels in the cell bodies but only by L-type Ca channels in the axons. This differential contribution of VGCC subtypes to calcium signals in RGC somata and their axons may provide insight into the development of target-specific strategies to spare the loss of RGCs and their axons following injury. C1 [Sargoy, Allison; Sun, Xiaoping; Barnes, Steven; Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. [Sargoy, Allison; Sun, Xiaoping; Barnes, Steven; Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Barnes, Steven; Brecha, Nicholas C.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Barnes, Steven] Dalhousie Univ, Dept Physiol & Biophys, Halifax, NS, Canada. [Barnes, Steven] Dalhousie Univ, Dept Ophthalmol & Visual Sci, Halifax, NS, Canada. RP Barnes, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. EM sbarnes@dal.ca FU NIH [EY04067]; VA Merit Review; CIHR; NSHRF Regional Partnership Program; NSERC; U.S. Army Medical Research & Materiel Command (USAMRMC); Telemedicine & Advanced Technology Research Center (TATRC) at Fort Detrick, MD [W81XWH-10-2-0077] FX Support for these studies came from NIH EY04067 (NCB), a VA Merit Review (NCB), a CIHR and NSHRF Regional Partnership Program grant (SB), and NSERC (SB). Part of this work was made possible by a contract agreement awarded to NCB and administered by the U.S. Army Medical Research & Materiel Command (USAMRMC) and the Telemedicine & Advanced Technology Research Center (TATRC) at Fort Detrick, MD under Contract Number: W81XWH-10-2-0077. NCB is a VA Senior Career Research Scientist. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 65 TC 9 Z9 9 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 8 PY 2014 VL 9 IS 1 AR e84507 DI 10.1371/journal.pone.0084507 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 291WL UT WOS:000329862500133 PM 24416240 ER PT J AU Sproul, AA Jacob, S Pre, D Kim, SH Nestor, MW Navarro-Sobrino, M Santa-Maria, I Zimmer, M Aubry, S Steele, JW Kahler, DJ Dranovsky, A Arancio, O Crary, JF Gandy, S Noggle, SA AF Sproul, Andrew A. Jacob, Samson Pre, Deborah Kim, Soong Ho Nestor, Michael W. Navarro-Sobrino, Miriam Santa-Maria, Ismael Zimmer, Matthew Aubry, Soline Steele, John W. Kahler, David J. Dranovsky, Alex Arancio, Ottavio Crary, John F. Gandy, Sam Noggle, Scott A. TI Characterization and Molecular Profiling of PSEN1 Familial Alzheimer's Disease iPSC-Derived Neural Progenitors SO PLOS ONE LA English DT Article ID PLURIPOTENT STEM-CELLS; 21ST-CENTURY BRAIN BANKING; NEURONAL GENE-EXPRESSION; COLUMBIA-UNIVERSITY; ADULT NEUROGENESIS; TRANSGENIC MICE; HUMAN ES; A-BETA; PRESENILIN-1; ACTIVATION AB Presenilin 1 (PSEN1) encodes the catalytic subunit of gamma-secretase, and PSEN1 mutations are the most common cause of early onset familial Alzheimer's disease (FAD). In order to elucidate pathways downstream of PSEN1, we characterized neural progenitor cells (NPCs) derived from FAD mutant PSEN1 subjects. Thus, we generated induced pluripotent stem cells (iPSCs) from affected and unaffected individuals from two families carrying PSEN1 mutations. PSEN1 mutant fibroblasts, and NPCs produced greater ratios of A beta 42 to A beta 40 relative to their control counterparts, with the elevated ratio even more apparent in PSEN1 NPCs than in fibroblasts. Molecular profiling identified 14 genes differentially-regulated in PSEN1 NPCs relative to control NPCs. Five of these targets showed differential expression in late onset AD/Intermediate AD pathology brains. Therefore, in our PSEN1 iPSC model, we have reconstituted an essential feature in the molecular pathogenesis of FAD, increased generation of A beta 42/40, and have characterized novel expression changes. C1 [Sproul, Andrew A.; Jacob, Samson; Nestor, Michael W.; Zimmer, Matthew; Kahler, David J.; Noggle, Scott A.] New York Stem Cell Fdn, New York, NY 10023 USA. [Pre, Deborah; Santa-Maria, Ismael; Aubry, Soline; Arancio, Ottavio; Crary, John F.] Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA. [Pre, Deborah; Santa-Maria, Ismael; Aubry, Soline; Arancio, Ottavio; Crary, John F.] Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA. [Kim, Soong Ho; Steele, John W.; Gandy, Sam] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY USA. [Kim, Soong Ho; Steele, John W.; Gandy, Sam] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY USA. [Kim, Soong Ho; Steele, John W.; Gandy, Sam] Icahn Sch Med Mt Sinai, Alzheimers Dis Res Ctr, New York, NY USA. [Navarro-Sobrino, Miriam; Dranovsky, Alex] Columbia Univ, Dept Psychiat, New York, NY USA. [Gandy, Sam] James J Peters Vet Adm Med Ctr, Bronx, NY USA. RP Sproul, AA (reprint author), New York Stem Cell Fdn, New York, NY 10023 USA. EM asproul@nsycf.org; snoggle@nyscf.org OI Sproul, Andrew/0000-0001-6972-1592 FU Charles Evans Foundation; Alzheimer's Drug Discovery Foundation; NY Community Trust; National Institutes of Health (NIH) [R21AG042965, 1U01AG046170-01, NS049442, R01MH091844]; Cure Alzheimer's Fund; BrightFocus Foundation; Taub Institute; Aging Brain at Columbia University [P50AG08702, RO1AG037212, P01AG07232] FX This work is generously supported by grants to Scott Noggle by Charles Evans Foundation, Alzheimer's Drug Discovery Foundation, and NY Community Trust. Scott Noggle and Sam Gandy are jointly supported by National Institutes of Health (NIH) grants R21AG042965 and 1U01AG046170-01, and the Cure Alzheimer's Fund. Ottavio Arancio is supported by NIH grant NS049442. Alex Dranovsky is supported by NIH grant R01MH091844. Soong Ho Kim is supported by the BrightFocus Foundation. The authors express their sincerest gratitude to the patients and staff of the Taub Institute for Research on Alzheimer's Disease & the Aging Brain at Columbia University (P50AG08702, RO1AG037212, P01AG07232). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 28 Z9 31 U1 5 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 JAN 8 PY 2014 VL 9 IS 1 AR e84547 DI 10.1371/journal.pone.0084547 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 291WL UT WOS:000329862500135 PM 24416243 ER PT J AU Walsh, ME Shi, Y Van Remmen, H AF Walsh, Michael E. Shi, Yun Van Remmen, Holly TI The effects of dietary restriction on oxidative stress in rodents SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE Dietary restriction; Calorie restriction; Oxidative stress; Reactive oxygen species; Antioxidant enzymes; Oxidative damage; Aging ID TERM CALORIE RESTRICTION; OXYGEN SPECIES PRODUCTION; SKELETAL-MUSCLE MITOCHONDRIA; RAT-LIVER MITOCHONDRIA; SUPEROXIDE DISMUTASE/CATALASE MIMETICS; AMYOTROPHIC-LATERAL-SCLEROSIS; HYDROGEN-PEROXIDE PRODUCTION; GLUTATHIONE REDOX STATE; DIFFERENT BRAIN-REGIONS; AGE-RELATED INCREASE AB Oxidative stress is observed during aging and in numerous age-related diseases. Dietary restriction (DR) is a regimen that protects against disease and extends life span in multiple species. However, it is unknown how DR mediates its protective effects. One prominent and consistent effect of DR in a number of systems is the ability to reduce oxidative stress and damage. The purpose of this review is to comprehensively examine the hypothesis that dietary restriction reduces oxidative stress in rodents by decreasing reactive oxygen species (ROS) production and increasing antioxidant enzyme activity, leading to an overall reduction of oxidative damage to macromolecules. The literature reveals that the effects of DR on oxidative stress are complex and likely influenced by a variety of factors, including sex, species, tissue examined, types of ROS and antioxidant enzymes examined, and duration of DR. Here we present a comprehensive review of the existing literature on the effect of DR on mitochondrial ROS generation, antioxidant enzymes, and oxidative damage. In a majority of studies, dietary restriction had little effect on mitochondrial ROS production or antioxidant activity. On the other hand, DR decreased oxidative damage in the majority of cases. Although the effects of DR on endogenous antioxidants are mixed, we find that glutathione levels are the most likely antioxidant to be increased by dietary restriction, which supports the emerging redox-stress hypothesis of aging. Published by Elsevier Inc. C1 [Walsh, Michael E.; Shi, Yun; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78245 USA. [Shi, Yun; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Van Remmen, Holly] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Van Remmen, H (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM vanremmen@uthscsa.edu FU NIA Training Grant on the Biology of Aging [T32AG021890]; National Institutes of Health - National Institute on Aging Grant [P01AG20591] FX This work was supported by an NIA Training Grant on the Biology of Aging (M.E.W., T32AG021890) and a National - Institutes of Health National Institute on Aging Grant (H.V.R., P01AG20591). NR 229 TC 19 Z9 19 U1 0 U2 23 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JAN 8 PY 2014 VL 66 SI SI BP 88 EP 99 DI 10.1016/j.freeradbiomed.2013.05.037 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 287SQ UT WOS:000329562900011 PM 23743291 ER PT J AU Kam-Hansen, S Jakubowski, M Kelley, JM Kirsch, I Hoaglin, DC Kaptchuk, TJ Burstein, R AF Kam-Hansen, Slavenka Jakubowski, Moshe Kelley, John M. Kirsch, Irving Hoaglin, David C. Kaptchuk, Ted J. Burstein, Rami TI Altered Placebo and Drug Labeling Changes the Outcome of Episodic Migraine Attacks SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; EXPECTATION; RESPONSES; PAIN; ACTIVATION; DISEASE AB Information provided to patients is thought to influence placebo and drug effects. In a prospective, within-subjects, repeated-measures study of 66 subjects with episodic migraine, we investigated how variations in medication labeling modified placebo and drug effects. An initial attack with no treatment served as a control. In six subsequent migraine attacks, each participant received either placebo or Maxalt (10-mg rizatriptan) administered under three information conditions ranging from negative to neutral to positive (told placebo, told Maxalt or placebo, told Maxalt) (N = 459 documented attacks). Treatment order was randomized. Maxalt was superior to placebo for pain relief. When participants were given placebo labeled as (i) placebo, (ii) Maxalt or placebo, and (iii) Maxalt, the placebo effect increased progressively. Maxalt had a similar progressive boost when labeled with these three labels. The efficacies of Maxalt labeled as placebo and placebo labeled as Maxalt were similar. The efficacy of open-label placebo was superior to that of no treatment. Relative to no treatment, the placebo, under each information condition, accounted for more than 50% of the drug effect. Increasing "positive" information incrementally boosted the efficacy of both placebo and medication during migraine attacks. The benefits of placebo persisted even if placebo was honestly described. Whether treatment involves medication or placebo, the information provided to patients and the ritual of pill taking are important components of care. C1 [Kam-Hansen, Slavenka] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Jakubowski, Moshe; Burstein, Rami] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02215 USA. [Kelley, John M.] Endicott Coll, Dept Psychol, Beverly, MA 01915 USA. [Kelley, John M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kelley, John M.; Kirsch, Irving; Kaptchuk, Ted J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Program Placebo Studies & Therapeut Encounter, Boston, MA 02215 USA. [Kirsch, Irving] Univ Plymouth, Sch Psychol, Plymouth PL4 8AA, Devon, England. RP Burstein, R (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02215 USA. EM rburstei@bidmc.harvard.edu FU Merck and Co. Inc.; NIH [R01 NS069847, R37 NS079678]; NIH National Center for Complementary and Alternative Medicine [K24 AT004095]; Blue Guitar Foundation FX Primary funding source: Merck and Co. Inc. R.B. received grant support from Merck and Co. Inc. and from the NIH (R01 NS069847, R37 NS079678). T.J.K. and J.M.K. were partially supported by NIH National Center for Complementary and Alternative Medicine (K24 AT004095). T.J.K. was partially funded by the Blue Guitar Foundation. No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript both on the submission form and in the text of the manuscript. NR 21 TC 32 Z9 32 U1 3 U2 19 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JAN 8 PY 2014 VL 6 IS 218 AR 218ra5 DI 10.1126/scitranslmed.3006175 PG 7 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 290WQ UT WOS:000329789600004 PM 24401940 ER PT J AU Evins, AE Cather, C Pratt, SA Pachas, GN Hoeppner, SS Goff, DC Achtyes, ED Ayer, D Schoenfeld, DA AF Evins, A. Eden Cather, Corinne Pratt, Sarah A. Pachas, Gladys N. Hoeppner, Susanne S. Goff, Donald C. Achtyes, Eric D. Ayer, David Schoenfeld, David A. TI Maintenance Treatment With Varenicline for Smoking Cessation in Patients With Schizophrenia and Bipolar Disorder A Randomized Clinical Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PLACEBO-CONTROLLED TRIAL; NICOTINE REPLACEMENT THERAPY; DOUBLE-BLIND; SCHIZOAFFECTIVE DISORDER; SUSTAINED-RELEASE; DEPRESSION SCALE; RATING-SCALE; BUPROPION; SAFETY; DEPENDENCE AB IMPORTANCE It is estimated that more than half of those with serious mental illness smoke tobacco regularly. Standard courses of pharmacotherapeutic cessation aids improve short-term abstinence, but most who attain abstinence relapse rapidly after discontinuation of pharmacotherapy. OBJECTIVE To determine whether smokers diagnosed with schizophrenia and bipolar disease have higher rates of prolonged tobacco abstinence with maintenance pharmacotherapy than with standard treatment. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, placebo-controlled, parallel-group, relapse-prevention clinical trial conducted in 10 community mental-health centers. Of 247 smokers with schizophrenia or bipolar disease recruited from March 2008-April 2012, 203 received 12-weeks' open-label varenicline and cognitive behavioral therapy and 87 met abstinence criteria to enter the relapse prevention intervention. INTERVENTIONS Participants who had 2 weeks or more of continuous abstinence at week 12 of open treatment were randomly assigned to receive cognitive behavioral therapy and double-blind varenicline (1 mg, 2 per day) or placebo from weeks 12 to 52. Participants then discontinued study treatment and were followed up to week 76. MAIN OUTCOMES AND MEASURES Seven-day rate of continuous abstinence at study week 52, the end of the relapse-prevention phase, confirmed by exhaled carbon monoxide. Secondary outcomes were continuous abstinence rates for weeks 12 through 64 based on biochemically verified abstinence and weeks 12 through 76, based on self-reported smoking behavior. RESULTS Sixty-one participants completed the relapse-prevention phase; 26 discontinued participation (7 varenicline, 19 placebo) and were considered to have relapsed for the analyses; 18 of these had relapsed prior to dropout. At week 52, point-prevalence abstinence rates were 60% in the varenicline group (24 of 40) vs 19% (9 of 47) in the placebo group (odds ratio [OR], 6.2; 95% CI, 2.2-19.2; P <.001). From weeks 12 through 64, 45%(18 of 40) among those in the varenicline group vs 15%(7 of 47) in the placebo group were continuously abstinent (OR, 4.6; 95% CI, 1.5-15.7; P =.004), and from weeks 12 through 76, 30% (12 of 40) in the varenicline group vs 11% (5 of 47) in the placebo group were continuously abstinent (OR, 3.4; 95% CI, 1.02-13.6; P =.03). There were no significant treatment effects on psychiatric symptom ratings or psychiatric adverse events. CONCLUSIONS AND RELEVANCE Among smokers with serious mental illness who attained initial abstinence with standard treatment, maintenance pharmacotherapy with varenicline and cognitive behavioral therapy improved prolonged tobacco abstinence rates compared with cognitive behavioral therapy alone after 1 year of treatment and at 6 months after treatment discontinuation. C1 [Evins, A. Eden; Cather, Corinne; Pachas, Gladys N.; Hoeppner, Susanne S.; Schoenfeld, David A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Evins, A. Eden; Cather, Corinne; Pachas, Gladys N.; Hoeppner, Susanne S.; Schoenfeld, David A.] Harvard Univ, Sch Med, Boston, MA USA. [Pratt, Sarah A.] Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA. [Goff, Donald C.] NYU, Langone Med Ctr, New York, NY USA. [Achtyes, Eric D.] Cherry St Hlth Serv, Grand Rapids, MI USA. [Achtyes, Eric D.] Michigan State Univ, Coll Human Med, Grand Rapids, MI USA. [Ayer, David] Centerstone Res Inst, Bloomington, IN USA. [Ayer, David] Indiana Univ, Bloomington, IN 47405 USA. RP Evins, AE (reprint author), 60 Staniford St, Boston, MA 02114 USA. EM a_eden_evins@hms.harvard.edu RI Hoeppner, Susanne/C-4631-2015; Achtyes, Eric/M-6024-2016 OI Hoeppner, Susanne/0000-0003-2060-1666; Achtyes, Eric/0000-0001-8939-1535 FU National Institute on Drug Abuse [R01 DA021245]; Pfizer; Department of Health and Human Services, Substance Abuse and Mental Health Services Administration [05B1MACMHS] FX This study was funded by grants R01 DA021245 by National Institute on Drug Abuse with supplemental financial and material support from an investigator-initiated award from Pfizer for study medications and funding, and by 05B1MACMHS to the Massachusetts Department of Mental Health from the Department of Health and Human Services, Substance Abuse and Mental Health Services Administration, Treatment Strategies for Smoking Cessation in Patients with Schizophrenia to the North Suffolk Mental Health Association (Dr Evins). Pfizer provided study medication and supplemental support through an investigator-initiated award after the protocol was approved by the institutional review board and the data and safety monitoring board. NR 32 TC 67 Z9 68 U1 4 U2 21 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 8 PY 2014 VL 311 IS 2 BP 145 EP 154 DI 10.1001/jama.2013.285113 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 284SA UT WOS:000329339400020 PM 24399553 ER PT J AU Martin, SS Blaha, MJ Blankstein, R Agatston, A Rivera, JJ Virani, SS Ouyang, P Jones, SR Blumenthal, RS Budoff, MJ Nasir, K AF Martin, Seth S. Blaha, Michael J. Blankstein, Ron Agatston, Arthur Rivera, Juan J. Virani, Salim S. Ouyang, Pamela Jones, Steven R. Blumenthal, Roger S. Budoff, Matthew J. Nasir, Khurram TI Dyslipidemia, Coronary Artery Calcium, and Incident Atherosclerotic Cardiovascular Disease Implications for Statin Therapy From the Multi-Ethnic Study of Atherosclerosis SO CIRCULATION LA English DT Article DE atherosclerosis; cardiovascular diseases; cholesterol; computed tomography ID C-REACTIVE PROTEIN; RISK; GUIDELINES; CHOLESTEROL; EVENTS; TRIALS; SCORE; MESA; RECOMMENDATIONS; INDIVIDUALS AB Background-Worldwide clinical practice guidelines for dyslipidemia emphasize allocating statin therapy to those at the highest absolute atherosclerotic cardiovascular disease (CVD) risk. Methods and Results-We examined 5534 Multi-Ethnic Study of Atherosclerosis (MESA) participants who were not on baseline medications for dyslipidemia. Participants were classified by baseline coronary artery calcium (CAC) score (>0, >= 100) and the common clinical scheme of counting lipid abnormalities (LA), including low-density lipoprotein cholesterol >= 3.36 mmol/L (130 mg/dL), high-density lipoprotein cholesterol <1.03 mmol/L (40 mg/dL) for men or <1.29 mmol/L (50 mg/dL) for women, and triglycerides >= 1.69 mmol/L (150 mg/dL). Our main outcome measure was incident CVD (myocardial infarction, angina resulting in revascularization, resuscitated cardiac arrest, stroke, cardiovascular death). Over a median follow-up of 7.6 years, more than half of events (55%) occurred in the 21% of participants with CAC >= 100. Conversely, 65% of events occurred in participants with 0 or 1 LA. In those with CAC >= 100, CVD rates ranged from 22.7 to 29.5 per 1000 person-years across LA categories. In contrast, with CAC=0, CVD rates ranged from 2.7 to 5.9 per 1000 person-years across LA categories. Individuals with 0 LA and CAC >= 100 had a higher event rate compared with individuals with 3 LA but CAC=0 (22.7 versus 5.9 per 1000 person-years). Similar results were obtained when we classified LA using data set quartiles of total cholesterol/high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, or low-density lipoprotein particle concentration and guideline categories of low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol. Conclusions-CAC may have the potential to help match statin therapy to absolute CVD risk. Across the spectrum of dyslipidemia, event rates similar to secondary prevention populations were observed for patients with CAC >= 100. C1 [Martin, Seth S.; Blaha, Michael J.; Ouyang, Pamela; Jones, Steven R.; Blumenthal, Roger S.; Nasir, Khurram] Johns Hopkins Ciccarone Ctr Prevent Heart Dis, Baltimore, MD USA. [Blankstein, Ron] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Noninvas Cardiovasc Imaging Program, Boston, MA 02115 USA. [Blankstein, Ron] Brigham & Womens Hosp, Boston, MA 02115 USA. [Agatston, Arthur] Univ Miami, South Beach Prevent Cardiol Ctr, Miami, FL USA. [Rivera, Juan J.] Columbia Univ, Div Cardiol, Mt Sinai Med Ctr, Miami Beach, FL USA. [Virani, Salim S.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Budoff, Matthew J.] Harbor Univ Calif Los Angeles Med Ctr, Div Cardiol, Los Angeles, CA USA. [Nasir, Khurram] Baptist Hlth Med Grp, Ctr Prevent & Wellness Res, Miami, FL USA. [Nasir, Khurram] Baptist Hlth South Florida, Baptist Cardiovasc Inst, Miami, FL USA. [Nasir, Khurram] Florida Int Univ, Robert Stempel Coll Publ Hlth, Dept Epidemiol, Miami, FL 33199 USA. [Nasir, Khurram] Herbert Wertheim Coll Med, Dept Med, Miami, FL USA. RP Nasir, K (reprint author), Baptist Hlth South Florida, Ctr Wellness & Prevent, 1691 Michigan Ave,Suite 500, Miami Beach, FL 33139 USA. EM khurramn@baptisthealth.net OI Virani, Salim/0000-0001-9541-6954 FU Pollin Cardiovascular Prevention Fellowship; Marie-Josee and Henry R. Kravis endowed fellowship; National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95169] FX Dr Martin is supported by the Pollin Cardiovascular Prevention Fellowship, as well as the Marie-Josee and Henry R. Kravis endowed fellowship. MESA, which supplied the data for this analysis, was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute. A group of individual investigators proposed and undertook the present study, for which we did not have any specific funding. National Heart, Lung, and Blood Institute-sponsored MESA committees reviewed and approved the proposal, abstract, and manuscript from the present study. Drs Martin and Nasir had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 24 TC 53 Z9 55 U1 0 U2 10 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 JAN 7 PY 2014 VL 129 IS 1 BP 77 EP + DI 10.1161/CIRCULATIONAHA.113.003625 PG 16 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AI2YY UT WOS:000336726300013 PM 24141324 ER PT J AU Hawkins, MS Hough, LJ Berger, MA Mor, MK Steenkiste, AR Gao, SS Stone, RA Burkitt, KH Marcus, BH Ciccolo, JT Kriska, AM Klinvex, DT Sevick, MA AF Hawkins, Marquis S. Hough, Linda J. Berger, Marie A. Mor, Maria K. Steenkiste, Ann R. Gao, Shasha Stone, Roslyn A. Burkitt, Kelly H. Marcus, Bess H. Ciccolo, Joseph T. Kriska, Andrea M. Klinvex, Deborah T. Sevick, Mary A. TI Recruitment of veterans from primary care into a physical activity randomized controlled trial: the experience of the VA-STRIDE study SO TRIALS LA English DT Article DE Veterans; Primary care; Physical activity; Overweight; Randomized controlled trial AB Background: Much of the existing literature on physical activity (PA) interventions involves physically inactive individuals recruited from community settings rather than clinical practice settings. Recruitment of patients into interventions in clinical practice settings is difficult due to limited time available in the clinic, identification of appropriate personnel to efficiently conduct the process, and time-consuming methods of recruitment. The purpose of this report is to describe the approach used to identify and recruit veterans from the Veterans Affairs (VA) Pittsburgh Healthcare System Primary Care Clinic into a randomized controlled PA study. Methods: A sampling frame of veterans was developed using the VA electronic medical record. During regularly scheduled clinic appointments, primary care providers (PCPs) screened identified patients for safety to engage in moderate-intensity PA and willingness to discuss the study with research staff members. Research staff determined eligibility with a subsequent telephone screening call and scheduled a research study appointment, at which time signed informed consent and baseline measurements were obtained. Results: Of the 3,482 veterans in the sampling frame who were scheduled for a primary care appointment during the study period, 1,990 (57.2%) were seen in the clinic and screened by the PCP; moderate-intensity PA was deemed safe for 1,293 (37.1%), 871 (25.0%) agreed to be contacted for further screening, 334 (9.6%) were eligible for the study, and 232 (6.7%) enrolled. Conclusions: Using a semiautomated screening approach that combined an electronically-derived sampling frame with paper and pencil prescreening by PCPs and research staff, VA-STRIDE was able to recruit 1 in 15 veterans in the sampling frame. Using this approach, a high proportion of potentially eligible veterans were screened by their PCPs. C1 [Hawkins, Marquis S.] Univ Massachusetts, Amherst Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA. [Hough, Linda J.; Berger, Marie A.; Mor, Maria K.; Steenkiste, Ann R.; Gao, Shasha; Stone, Roslyn A.; Burkitt, Kelly H.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Mor, Maria K.; Stone, Roslyn A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15260 USA. [Marcus, Bess H.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Ciccolo, Joseph T.] Columbia Univ Teachers Coll, Dept Biobehav Sci, New York, NY 10027 USA. [Kriska, Andrea M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Klinvex, Deborah T.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA 15260 USA. [Sevick, Mary A.] NYU, Sch Med, Dept Populat Hlth, New York, NY 10016 USA. RP Hawkins, MS (reprint author), Univ Massachusetts, Amherst Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA. EM mshawkins@schoolph.umass.edu OI Kriska, Andrea/0000-0002-3522-0869 FU Veterans' Administration Health Services Research and Development Service [IIR 07-154] FX This work was supported by the Veterans' Administration Health Services Research and Development Service under award IIR 07-154, and by resources and the use of facilities at the VA Pittsburgh Healthcare System. The authors are grateful for the contributions of Erika Hoffman, MD (Medical Director), and the PCPs and clinic staff from VAPHS UD for screening potential participants; the assistance of Kathleen Sward, PhD, and Robert M Powell, MS, for participant recruitment, PA counseling, and assessments; and Deborah Wetzler, BA, and D Scott Obrosky, MS, for data management and programming. NR 14 TC 2 Z9 2 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6215 J9 TRIALS JI Trials PD JAN 7 PY 2014 VL 15 AR 11 DI 10.1186/1745-6215-15-11 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AD7QY UT WOS:000333461000001 PM 24398076 ER PT J AU Li, TT Qiu, F Qian, ZR Wan, J Qi, XK Wu, BY AF Li, Ting-Ting Qiu, Feng Qian, Zhi Rong Wan, Jun Qi, Xiao-Kun Wu, Ben-Yan TI Classification, clinicopathologic features and treatment of gastric neuroendocrine tumors SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Review DE Gastric neuroendocrine tumor; Classification; Clinicopathological significance; Diagnosis; Prognosis; Treatment ID OF-THE-LITERATURE; NEOPLASIA TYPE-I; RECEPTOR ANTAGONIST; CARCINOID-TUMORS; HEALTHY-SUBJECTS; GASTROENTEROPANCREATIC TUMORS; SOMATOSTATIN ANALOGS; NETAZEPIDE YF476; FOLLOW-UP; C-KIT AB Gastric neuroendocrine tumors (GNETs) are rare lesions characterized by hypergastrinemia that arise from enterochromaffin-like cells of the stomach. GNETs consist of a heterogeneous group of neoplasms comprising tumor types of varying pathogenesis, histomorphologic characteristics, and biological behavior. A classification system has been proposed that distinguishes four types of GNETs; the clinicopathological features of the tumor, its prognosis, and the patient's survival strictly depend on this classification. Thus, correct management of patients with GNETs can only be proposed when the tumor has been classified by an accurate pathological and clinical evaluation of the patient. Recently developed cancer therapies such as inhibition of angiogenesis or molecular targeting of growth factor receptors have been used to treat GNETs, but the only definitive therapy is the complete resection of the tumor. Here we review the literature on GNETs, and summarize the classification, clinicopathological features (especially prognosis), clinical presentations and current practice of management of GNETs. We also present the latest findings on new gene markers for GNETs, and discuss the effective drugs developed for the diagnosis, prognosis and treatment of GNETs. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved. C1 [Li, Ting-Ting; Wan, Jun; Wu, Ben-Yan] Chinese Peoples Liberat Army Gen Hosp, Dept Geriatr Gastroenterol, Beijing 100853, Peoples R China. [Qiu, Feng; Qi, Xiao-Kun] Chinese Navy Gen Hosp, Dept Neurol, Beijing 100048, Peoples R China. [Qian, Zhi Rong] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Wu, BY (reprint author), Chinese Peoples Liberat Army Gen Hosp, Dept Geriatr Gastroenterol, 28 Fuxing Rd, Beijing 100853, Peoples R China. EM benyanwu@vip.sina.com FU National Natural Scientific Foundation of China [B1070296] FX Supported by National Natural Scientific Foundation of China, No. B1070296 NR 71 TC 13 Z9 15 U1 0 U2 6 PU BAISHIDENG PUBL GRP CO LTD PI WANCHAI PA ROOM 1701, 17-F, HENAN BUILDING, NO. 90, JAFFE RD, WANCHAI, HONG KONG 100025, PEOPLES R CHINA SN 1007-9327 EI 2219-2840 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD JAN 7 PY 2014 VL 20 IS 1 BP 118 EP 125 DI 10.3748/wjg.v20.i1.118 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AA1KR UT WOS:000330855600013 PM 24415864 ER PT J AU Jones, SS Rudin, RS Perry, T Shekelle, PG AF Jones, Spencer S. Rudin, Robert S. Perry, Tanja Shekelle, Paul G. TI Health Information Technology: An Updated Systematic Review With a Focus on Meaningful Use SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID CLINICAL DECISION-SUPPORT; PROVIDER ORDER ENTRY; MEDICATION ERRORS; PATIENT OUTCOMES; CARE; MANAGEMENT; EFFICIENCY; IMPROVE; QUALITY; RECORDS AB Background: Incentives offered by the U.S. government have spurred marked increases in use of health information technology (IT). Purpose: To update previous reviews and examine recent evidence that relates health IT functionalities prescribed in meaningful use regulations to key aspects of health care. Data Sources: English-language articles in PubMed from January 2010 to August 2013. Study Selection: 236 studies, including pre-post and time-series designs and clinical trials that related the use of health IT to quality, safety, or efficiency. Data Extraction: Two independent reviewers extracted data on functionality, study outcomes, and context. Data Synthesis: Fifty-seven percent of the 236 studies evaluated clinical decision support and computerized provider order entry, whereas other meaningful use functionalities were rarely evaluated. Fifty-six percent of studies reported uniformly positive results, and an additional 21% reported mixed-positive effects. Reporting of context and implementation details was poor, and 61% of studies did not report any contextual details beyond basic information. Limitation: Potential for publication bias, and evaluated health IT systems and outcomes were heterogeneous and incompletely described. Conclusion: Strong evidence supports the use of clinical decision support and computerized provider order entry. However, insufficient reporting of implementation and context of use makes it impossible to determine why some health IT implementations are successful and others are not. The most important improvement that can be made in health IT evaluations is increased reporting of the effects of implementation and context. C1 RAND Corp, Santa Monica, CA USA. Soutern Calif Evidence Based Practice Ctr, Santa Monica, CA USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. Vanguard Hlth Syst, Nashville, TN USA. RP Jones, SS (reprint author), RAND Hlth, Southern Calif Evidence Based Practice Ctr, 1776 Main St, Santa Monica, CA 90401 USA. EM spencer.jones@vanguardhealth.com FU Office of the National Coordinator FX Office of the National Coordinator. NR 38 TC 77 Z9 78 U1 3 U2 27 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 7 PY 2014 VL 160 IS 1 BP 48 EP + DI 10.7326/M13-1531 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 297IS UT WOS:000330249700006 PM 24573664 ER PT J AU Elman, JS Li, M Wang, FJ Gimble, JM Parekkadan, B AF Elman, Jessica S. Li, Matthew Wang, Fangjing Gimble, Jeffrey M. Parekkadan, Biju TI A comparison of adipose and bone marrow-derived mesenchymal stromal cell secreted factors in the treatment of systemic inflammation SO JOURNAL OF INFLAMMATION-LONDON LA English DT Article DE Soluble receptors; Mesenchymal stem cells; Adipose stem cells; Endotoxic shock; Tissue necrosis factor alpha (TNF-alpha); Vascular endothelial growth factor (VEGF) ID STEM-CELLS; IN-VIVO; SEPSIS; MECHANISMS; RECEPTORS; MICE AB Background: Bone marrow-derived mesenchymal stromal cells (BMSCs) are a cell population of intense exploration for therapeutic use in inflammatory diseases. Secreted factors released by BMSCs are responsible for the resolution of inflammation in several pre-clinical models. New studies have uncovered that adipose tissue also serves as a reservoir of multipotent, non-hematopoietic stem cells, termed adipose-derived stromal/stem cells (ASCs), with many common characteristics to BMSCs. We hypothesized that ASC and BMSC secreted factors would lead to a comparable benefit in the context of generalized inflammation. Findings: Proteomic profiling of conditioned media revealed that BMSCs express significantly higher levels of sVEGFR1 and sTNFR1, two soluble cytokine receptors with known therapeutic activity in sepsis. In a prophylactic study of endotoxin-induced inflammation in mice, we observed that BMSC secreted factors provided a greater survival benefit and tissue protection of endotoxemic mice compared to ASCs. Neutralization of sVEGFR1 and sTNFR1 did not significantly affect the survival benefit experienced by mice treated with BMSC secreted factors. Conclusions: Our findings suggest that BMSCs may be more effective as a cell therapeutic for use in endotoxic shock and that ASCs may be positioned for continued exploration in immunomodulatory diseases. Soluble cytokine receptors can distinguish stromal cells from different tissue origins, though they may not be the sole contributors to the therapeutic benefit of BMSCs. Furthermore, other secreted factors not discussed in this study may also differentiate these stromal cell populations from one another. C1 [Elman, Jessica S.; Wang, Fangjing; Parekkadan, Biju] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. [Elman, Jessica S.; Wang, Fangjing; Parekkadan, Biju] Shriners Hosp Children Boston, Boston, MA 02114 USA. [Li, Matthew] Harvard MIT Hlth Sci & Technol, Cambridge, MA 02139 USA. [Gimble, Jeffrey M.] Louisiana State Univ, Pennington Biomed Res Ctr, Stem Cell Biol Lab, Baton Rouge, LA 70808 USA. [Parekkadan, Biju] Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Parekkadan, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. EM biju_parekkadan@hms.harvard.edu FU National Institutes of Health [R01EB012521, K01DK087770]; Broad Medical Research Program of The Broad Foundation [BMRP498382]; Shriners Hospitals for Children FX This work was supported of the National Institutes of Health (R01EB012521 and K01DK087770) and the Broad Medical Research Program of The Broad Foundation (BMRP498382) and Shriners Hospitals for Children. NR 24 TC 23 Z9 25 U1 1 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-9255 J9 J INFLAMM-LOND JI J. Inflamm.-Lond. PD JAN 7 PY 2014 VL 11 AR 1 DI 10.1186/1476-9255-11-1 PG 8 WC Immunology SC Immunology GA 298KA UT WOS:000330321500001 PM 24397734 ER PT J AU Ivanova, MI Sievers, SA Guenther, EL Johnson, LM Winkler, DD Galaleldeen, A Sawaya, MR Hart, PJ Eisenberg, DS AF Ivanova, Magdalena I. Sievers, Stuart A. Guenther, Elizabeth L. Johnson, Lisa M. Winkler, Duane D. Galaleldeen, Ahmad Sawaya, Michael R. Hart, P. John Eisenberg, David S. TI Aggregation-triggering segments of SOD1 fibril formation support a common pathway for familial and sporadic ALS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE protein aggregation; peptide structure; amyotrophic lateral sclerosis ID AMYOTROPHIC-LATERAL-SCLEROSIS; ZINC SUPEROXIDE-DISMUTASE; COPPER-BINDING-SITE; WILD-TYPE; TRANSGENIC MICE; MOLECULAR-BASIS; MUTATION; INCLUSIONS; INSIGHTS AB ALS is a terminal disease of motor neurons that is characterized by accumulation of proteinaceous deposits in affected cells. Pathological deposition of mutated Cu/Zn superoxide dismutase (SOD1) accounts for similar to 20% of the familial ALS (fALS) cases. However, understanding the molecular link between mutation and disease has been difficult, given that more than 140 different SOD1 mutants have been observed in fALS patients. In addition, the molecular origin of sporadic ALS (sALS) is unclear. By dissecting the amino acid sequence of SOD1, we identified four short segments with a high propensity for amyloid fibril formation. We find that fALS mutations in these segments do not reduce their propensity to form fibrils. The atomic structures of two fibril-forming segments from the C terminus, (DSVISLS107)-D-101 and (147)GVIGIAQ(153), reveal tightly packed beta-sheets with steric zipper interfaces characteristic of the amyloid state. Based on these structures, we conclude that both C-terminal segments are likely to form aggregates if available for interaction. Proline substitutions in (DSVISLS107)-D-101 and (147)GVIGIAQ(153) impaired nucleation and fibril growth of full-length protein, confirming that these segments participate in aggregate formation. Our hypothesis is that improper protein maturation and incompletely folded states that render these aggregation-prone segments available for interaction offer a common molecular pathway for sALS and fALS. C1 [Ivanova, Magdalena I.; Sievers, Stuart A.; Guenther, Elizabeth L.; Johnson, Lisa M.; Sawaya, Michael R.; Eisenberg, David S.] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA. [Ivanova, Magdalena I.; Sievers, Stuart A.; Guenther, Elizabeth L.; Johnson, Lisa M.; Sawaya, Michael R.; Eisenberg, David S.] Univ Calif Los Angeles, UCLA DOE Inst Genom & Prote, Los Angeles, CA 90095 USA. [Ivanova, Magdalena I.; Sievers, Stuart A.; Guenther, Elizabeth L.; Johnson, Lisa M.; Sawaya, Michael R.; Eisenberg, David S.] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA. [Ivanova, Magdalena I.] Univ Michigan, Dept Neurol, Sch Med, Ann Arbor, MI 48109 USA. [Sievers, Stuart A.] CALTECH, Div Biol, Pasadena, CA 91125 USA. [Winkler, Duane D.; Galaleldeen, Ahmad; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Winkler, Duane D.] Univ Texas Dallas, Dept Mol & Cell Biol, Richardson, TX 75080 USA. [Galaleldeen, Ahmad] St Marys Univ, Dept Biol Sci, San Antonio, TX 78228 USA. [Hart, P. John] South Texas Vet Hlth Care Syst, Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Eisenberg, DS (reprint author), Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA. EM david@mbi.ucla.edu FU Howard Hughes Medical Institute [P01 NS049134]; National Institutes of Health [AG029430]; NIH; Department of Energy; Department of Veterans Affairs [1I01BX000506]; Judith and Jean Pape Adams Charitable Foundation; NIH [R01 NS39112] FX We thank Dr. L. Goldschmidt, Dr. M. Chattopadhyay, Dr. R. Nelson, Dr. B. Chan, and Prof. J. S. Valentine for discussions; Dr. I. Kourinov, Dr. J. Schuermann, Dr. K. Rajashankar, Dr. N. Sukumar, and Dr. S. Banerjee at Advanced Photon Source beamline 24-ID-E and European Synchrotron Radiation Facility beamline ID13 for help with X-ray data collection; Howard Hughes Medical Institute, P01 NS049134, National Institutes of Health AG029430, NIH P01, and Department of Energy for support to the D.E. laboratory; and Department of Veterans Affairs 1I01BX000506, the Judith and Jean Pape Adams Charitable Foundation, and NIH R01 NS39112 for support to the P.J.H. laboratory. NR 27 TC 25 Z9 26 U1 1 U2 11 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 7 PY 2014 VL 111 IS 1 BP 197 EP 201 DI 10.1073/pnas.1320786110 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 284VY UT WOS:000329350700062 PM 24344300 ER PT J AU Choi, YI Duke-Cohan, JS Chen, W Liu, BY Rossy, J Tabarin, T Ju, LN Gui, JG Gaus, K Zhu, C Reinherz, EL AF Choi, Young I. Duke-Cohan, Jonathan S. Chen, Wei Liu, Baoyu Rossy, Jeremie Tabarin, Thibault Ju, Lining Gui, Jingang Gaus, Katharina Zhu, Cheng Reinherz, Ellis L. TI Dynamic control of beta 1 integrin adhesion by the plexinD1-sema3E axis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE thymocyte development; mechanobiology; integrin activation; autoimmunity; central tolerance ID T-CELL DEVELOPMENT; FORMS CATCH BONDS; NEGATIVE SELECTION; STRUCTURAL BASIS; POSITIVE SELECTION; SLIP BONDS; THYMOCYTES; THYMUS; EXPRESSION; INTEGRIN AB Plexins and semaphorins comprise a large family of receptor-ligand pairs controlling cell guidance in nervous, immune, and vascular systems. How plexin regulation of neurite outgrowth, lymphoid trafficking, and vascular endothelial cell branching is linked to integrin function, central to most directed movement, remains unclear. Here we show that on developing thymocytes, plexinD1 controls surface topology of nanometer-scaled beta 1 integrin adhesion domains in cis, whereas its ligation by sema3E in trans regulates individual beta 1 integrin catch bonds. Loss of plexinD1 expression reduces beta 1 integrin clustering, thereby diminishing avidity, whereas sema3E ligation shortens individual integrin bond lifetimes under force to reduce stability. Consequently, both decreased expression of plexinD1 during developmental progression and a thymic medulla-emanating sema3E gradient enhance thymocyte movement toward the medulla, thus enforcing the orchestrated lymphoid trafficking required for effective immune repertoire selection. Our results demonstrate plexin-tunable molecular features of integrin adhesion with broad implications for many cellular processes. C1 [Choi, Young I.; Duke-Cohan, Jonathan S.; Gui, Jingang; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. [Choi, Young I.; Duke-Cohan, Jonathan S.; Gui, Jingang; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Choi, Young I.; Duke-Cohan, Jonathan S.; Gui, Jingang; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Chen, Wei; Liu, Baoyu; Ju, Lining; Zhu, Cheng] Georgia Inst Technol, Coulter Dept Biomed Engn, Atlanta, GA 30332 USA. [Chen, Wei; Liu, Baoyu; Ju, Lining; Zhu, Cheng] Georgia Inst Technol, Woodruff Sch Mech Engn, Atlanta, GA 30332 USA. [Chen, Wei; Liu, Baoyu; Ju, Lining; Zhu, Cheng] Georgia Inst Technol, Inst Bioengn & Biosci, Atlanta, GA 30332 USA. [Rossy, Jeremie; Tabarin, Thibault; Gaus, Katharina] Univ New S Wales, Ctr Vasc Res, Sydney, NSW 2052, Australia. [Rossy, Jeremie; Tabarin, Thibault; Gaus, Katharina] Univ New S Wales, Australian Ctr Nanomed, Sydney, NSW 2052, Australia. RP Reinherz, EL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu RI Chen, Wei/C-4823-2009; Liu, Baoyu/C-4911-2009; OI Liu, Baoyu/0000-0002-0798-6314; Ju, Lining/0000-0002-7591-0864 FU National Institutes of Health [AI19807, AI92378, AI44902]; Australian Research Council; National Health and Medical Research Council of Australia FX We thank Maris Handley and Elizabeth Witten for technical assistance. This work was supported by National Institutes of Health Grants AI19807 (to E.L.R.), AI92378 (to Y.I.C.), and AI44902 (to C.Z.), the Australian Research Council (K.G.), and the National Health and Medical Research Council of Australia (J.R. and K.G.). NR 49 TC 18 Z9 18 U1 2 U2 12 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 7 PY 2014 VL 111 IS 1 BP 379 EP 384 DI 10.1073/pnas.1314209111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 284VY UT WOS:000329350700093 PM 24344262 ER PT J AU Dose, M Emmanuel, AO Chaumeil, J Zhang, JW Sun, TJ Germar, K Aghajani, K Davis, EM Keerthivasan, S Bredemeyer, AL Sleckman, BP Rosen, ST Skok, JA Le Beau, MM Georgopoulos, K Gounari, F AF Dose, Marei Emmanuel, Akinola Olumide Chaumeil, Julie Zhang, Jiangwen Sun, Tianjiao Germar, Kristine Aghajani, Katayoun Davis, Elizabeth M. Keerthivasan, Shilpa Bredemeyer, Andrea L. Sleckman, Barry P. Rosen, Steven T. Skok, Jane A. Le Beau, Michelle M. Georgopoulos, Katia Gounari, Fotini TI beta-Catenin induces T-cell transformation by promoting genomic instability SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE beta-catenin/Tcf-1; DNA recombination Tcf7; Ctnnb1 ID ACUTE LYMPHOBLASTIC-LEUKEMIA; C-MYC ONCOGENE; V(D)J RECOMBINATION; THYMOCYTE SURVIVAL; DNA-DAMAGE; TRANSCRIPTION FACTORS; MURINE PLASMACYTOMAS; GENE AMPLIFICATION; TRANSLOCATIONS; BREAKPOINT AB Deregulated activation of beta-catenin in cancer has been correlated with genomic instability. During thymocyte development, beta-catenin activates transcription in partnership with T-cell-specific transcription factor 1 (Tcf-1). We previously reported that targeted activation of beta-catenin in thymocytes (CAT mice) induces lymphomas that depend on recombination activating gene (RAG) and myelocytomatosis oncogene (Myc) activities. Here we show that these lymphomas have recurring Tcra/Myc translocations that resulted from illegitimate RAG recombination events and resembled oncogenic translocations previously described in human T-ALL. We therefore used the CAT animal model to obtain mechanistic insights into the transformation process. ChIP-seq analysis uncovered a link between Tcf-1 and RAG2 showing that the two proteins shared binding sites marked by trimethylated histone-3 lysine-4 (H3K4me3) throughout the genome, including near the translocation sites. Pretransformed CAT thymocytes had increased DNA damage at the translocating loci and showed altered repair of RAG-induced DNA double strand breaks. These cells were able to survive despite DNA damage because activated beta-catenin promoted an antiapoptosis gene expression profile. Thus, activated beta-catenin promotes genomic instability that leads to T-cell lymphomas as a consequence of altered double strand break repair and increased survival of thymocytes with damaged DNA. C1 [Dose, Marei; Emmanuel, Akinola Olumide; Sun, Tianjiao; Germar, Kristine; Aghajani, Katayoun; Keerthivasan, Shilpa; Gounari, Fotini] Univ Chicago, Rheumatol Sect, Chicago, IL 60637 USA. [Dose, Marei; Emmanuel, Akinola Olumide; Sun, Tianjiao; Germar, Kristine; Aghajani, Katayoun; Keerthivasan, Shilpa; Gounari, Fotini] Univ Chicago, Knapp Ctr Lupus & Immunol Res, Chicago, IL 60637 USA. [Chaumeil, Julie; Skok, Jane A.] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. [Zhang, Jiangwen] Harvard Univ, FAS, Ctr Syst Biol, Cambridge, MA 02138 USA. [Davis, Elizabeth M.; Le Beau, Michelle M.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. [Davis, Elizabeth M.; Le Beau, Michelle M.] Univ Chicago, Ctr Comprehens Canc, Chicago, IL 60637 USA. [Bredemeyer, Andrea L.; Sleckman, Barry P.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Rosen, Steven T.] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Georgopoulos, Katia] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Gounari, F (reprint author), Univ Chicago, Rheumatol Sect, Chicago, IL 60637 USA. EM fgounari@uchicago.edu OI Dose, Marei/0000-0001-5394-9779; Bredemeyer, Andrea/0000-0003-2970-5998; Skok, Jane/0000-0002-4145-1516 FU National Institutes of Health [R21AI076720, R01CA158006, F31AI830542, R01GM086852]; American Cancer Society Grant ACS/RSG [LIB-113428]; Chicago Biomedical Consortium; Lady Tata Memorial Trust; Specialized Center of Research of the Leukemia and Lymphoma Society (LLS) [SCOR R7019-04] FX We thank D. Schatz, G. Teng, and H. Kawamoto for reagents; M. Clark, K. Khazaie, and D. Schatz for advice; and C. Daly, E. Bartom, and M. Maienshein-Cline for technical assistance and data mining. This work was supported by National Institutes of Health Grants R21AI076720 (to F.G.), R01CA158006 (to K. Georgopoulos), F31AI830542 (to K. Germar), and R01GM086852 (to J.A.S.), and R01CA158006 (to K. Georgopoulos). Further support came from the American Cancer Society Grant ACS/RSG, LIB-113428 (to F.G.); Chicago Biomedical Consortium (F.G.); The Lady Tata Memorial Trust (M.D.); and a Specialized Center of Research of the Leukemia and Lymphoma Society (LLS) [SCOR R7019-04 (M.M.L.B.)]. J.A.S. is an LLS scholar. J.C. is an Irvington Institute Fellow of the Cancer Research Institute. NR 53 TC 19 Z9 19 U1 1 U2 12 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 7 PY 2014 VL 111 IS 1 BP 391 EP 396 DI 10.1073/pnas.1315752111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 284VY UT WOS:000329350700095 PM 24371308 ER PT J AU Kuchibhotla, KV Wegmann, S Kopeikina, KJ Hawkes, J Rudinskiy, N Andermann, ML Spires-Jones, TL Bacskai, BJ Hyman, BT AF Kuchibhotla, Kishore V. Wegmann, Susanne Kopeikina, Katherine J. Hawkes, Jonathan Rudinskiy, Nikita Andermann, Mark L. Spires-Jones, Tara L. Bacskai, Brian J. Hyman, Bradley T. TI Neurofibrillary tangle-bearing neurons are functionally integrated in cortical circuits in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE paired helical filaments; tau pathology; neuronal networks ID A-BETA-PLAQUES; ALZHEIMERS-DISEASE; MOUSE MODEL; VISUAL-CORTEX; TAU; TAUOPATHY; MEMORY; NEURODEGENERATION; MICE; DYSFUNCTION AB Alzheimer's disease (AD) is pathologically characterized by the deposition of extracellular amyloid-beta plaques and intracellular aggregation of tau protein in neurofibrillary tangles (NFTs) (1, 2). Progression of NFT pathology is closely correlated with both increased neurodegeneration and cognitive decline in AD (3) and other tauopathies, such as frontotemporal dementia (4, 5). The assumption that mislocalization of tau into the somatodendritic compartment (6) and accumulation of fibrillar aggregates in NFTs mediates neurodegeneration underlies most current therapeutic strategies aimed at preventing NFT formation or disrupting existing NFTs (7, 8). Although several disease-associated mutations cause both aggregation of tau and neurodegeneration, whether NFTs per se contribute to neuronal and network dysfunction in vivo is unknown (9). Here we used awake in vivo two-photon calcium imaging to monitor neuronal function in adult rTg4510 mice that overexpress a human mutant form of tau (P301L) and develop cortical NFTs by the age of 7-8 mo (10). Unexpectedly, NFT-bearing neurons in the visual cortex appeared to be completely functionally intact, to be capable of integrating dendritic inputs and effectively encoding orientation and direction selectivity, and to have a stable baseline resting calcium level. These results suggest a reevaluation of the common assumption that insoluble tau aggregates are sufficient to disrupt neuronal function. C1 [Kuchibhotla, Kishore V.; Wegmann, Susanne; Kopeikina, Katherine J.; Hawkes, Jonathan; Rudinskiy, Nikita; Spires-Jones, Tara L.; Bacskai, Brian J.; Hyman, Bradley T.] Harvard Univ, MassGen Inst Neurodegenerat Dis, Massachusetts Gen Hosp, Alzheimers Dis Res Lab,Dept Neurol,Med Sch, Boston, MA 02129 USA. [Kuchibhotla, Kishore V.] NYU, Sch Med, Skirball Inst, New York, NY 10016 USA. [Kopeikina, Katherine J.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Andermann, Mark L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol,Dept Med, Boston, MA 02215 USA. [Spires-Jones, Tara L.] Univ Edinburgh Neurosci, Ctr Cognit & Neural Syst, Edinburgh EH8 9JZ, Midlothian, Scotland. RP Hyman, BT (reprint author), Harvard Univ, MassGen Inst Neurodegenerat Dis, Massachusetts Gen Hosp, Alzheimers Dis Res Lab,Dept Neurol,Med Sch, Boston, MA 02129 USA. EM bhyman@partners.org OI Spires-Jones, Tara/0000-0003-2530-0598 FU National Institutes of Health [R01 AG026249, EB000768]; German Research Foundation; American Federation for Aging Research FX We thank Dr. Eloise Hudry and Dr. Michal Arbel-Ornath for helpful discussions and Dr. Peter Davies for the PHF1 antibody. This work was supported by the National Institutes of Health (Grants R01 AG026249, to B. T. H., and EB000768, to B.J.B.). S. W. was supported by the German Research Foundation. This research was conducted while M. L. A. was a recipient of a New Investigator Award in Alzheimer's Disease from the American Federation for Aging Research. NR 33 TC 49 Z9 50 U1 2 U2 15 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 7 PY 2014 VL 111 IS 1 BP 510 EP 514 DI 10.1073/pnas.1318807111 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 284VY UT WOS:000329350700115 PM 24368848 ER PT J AU Tawakol, A Singh, P Rudd, JHF Soffer, J Cai, G Vucic, E Brannan, SP Tarka, EA Shaddinger, BC Sarov-Blat, L Matthews, P Subramanian, S Farkouh, M Fayad, ZA AF Tawakol, Ahmed Singh, Parmanand Rudd, James H. F. Soffer, Joseph Cai, Gengqian Vucic, Esad Brannan, Sarah P. Tarka, Elizabeth A. Shaddinger, Bonnie C. Sarov-Blat, Lea Matthews, Paul Subramanian, Sharath Farkouh, Michael Fayad, Zahi A. TI Effect of Treatment for 12 Weeks With Rilapladib, a Lipoprotein-Associated Phospholipase A(2) Inhibitor, on Arterial Inflammation as Assessed With F-18-Fluorodeoxyglucose-Positron Emission Tomography Imaging SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Letter ID PLAQUE INFLAMMATION; POSITRON; RISK C1 [Tawakol, Ahmed] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Tawakol, Ahmed; Singh, Parmanand; Vucic, Esad; Subramanian, Sharath] Harvard Univ, Sch Med, Boston, MA USA. [Singh, Parmanand; Vucic, Esad; Subramanian, Sharath] Massachusetts Gen Hosp, Div Cardiac Imaging, Cardiac MRPET CT Program, Boston, MA 02114 USA. [Rudd, James H. F.] Univ Cambridge, Div Cardiovasc Med, Cambridge, England. [Soffer, Joseph; Cai, Gengqian; Brannan, Sarah P.; Tarka, Elizabeth A.; Shaddinger, Bonnie C.; Sarov-Blat, Lea; Matthews, Paul] GlaxoSmithKline, Metab Pathways & Cardiovasc Therapeut Area, King Of Prussia, PA USA. [Matthews, Paul] Univ London Imperial Coll Sci Technol & Med, Div Brain Sci, London, England. [Farkouh, Michael; Fayad, Zahi A.] Icahn Sch Med Mt Sinai, Cardiovasc Inst, New York, NY USA. [Farkouh, Michael] Univ Toronto, Peter Munk Card Ctr, Toronto, ON, Canada. [Farkouh, Michael] Univ Toronto, Heart & Stroke Richard Lewar Ctr Excellence, Toronto, ON, Canada. [Fayad, Zahi A.] Icahn Sch Med Mt Sinai, Translat & Mol Imaging Inst, New York, NY USA. RP Tawakol, A (reprint author), Massachusetts Gen Hosp, Div Cardiol, 25 Shattuck St, Boston, MA 02114 USA. EM atawakol@partners.org OI Matthews, Paul M/0000-0002-1619-8328; Rudd, James/0000-0003-2243-3117 NR 5 TC 34 Z9 34 U1 0 U2 4 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 JAN 7 PY 2014 VL 63 IS 1 BP 86 EP 88 DI 10.1016/j.jacc.2013.07.050 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 291OO UT WOS:000329838300016 PM 23973698 ER PT J AU Bowers, E Scamurra, RW Asrani, A Beniguel, L MaWhinney, S Keays, KM Thurn, JR Janoff, EN AF Bowers, Elisabeth Scamurra, Ronald W. Asrani, Anil Beniguel, Lydie MaWhinney, Samantha Keays, Kathryne M. Thurn, Joseph R. Janoff, Edward N. TI Decreased Mutation Frequencies among Immunoglobulin G Variable Region Genes during Viremic HIV-1 Infection SO PLOS ONE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INDUCED CYTIDINE DEAMINASE; B-CELLS; SOMATIC HYPERMUTATION; CAPSULAR POLYSACCHARIDE; PNEUMOCOCCAL VACCINE; ANTIBODY-RESPONSE; LYMPHOID-TISSUE; DNA-REPAIR; IN-VIVO AB Background/Objective: HIV-1 infection is complicated by high rates of opportunistic infections against which specific antibodies contribute to immune defense. Antibody function depends on somatic hypermutation (SHM) of variable regions of immunoglobulin heavy chain genes (V-H-D-J). We characterized the frequency of SHM in expressed IgG mRNA immunoglobulin transcripts from control and HIV-1-infected patients. Design: We compared utilization of genes in the most prominent V-H family (V(H)3) and mutation frequencies and patterns of cDNA from V(H)3-IgG genes from 10 seronegative control subjects and 21 patients with HIV-1 infection (6 without and 15 patients with detectable plasma viremia). Methods: Unique IgG V(H)3 family cDNA sequences (n = 1,565) were PCR amplified, cloned, and sequenced from blood. Sequences were analyzed using online (Vbase) and in-house immunoglobulin alignment resources. Results: Mutation frequencies in the antigen-binding hypervariable complementarity determining regions (CDR1/2) of IgG class-switched B cells were lower among viremic HIV-1-infected patients vs. controls for nucleotides (CDR1/2: 10+/-5% vs. 13.5+/-6%, p = 0.03) and amino acids (CDR: 20%+/-10 vs. 25%+/-12, p = 0.02) and in structural framework regions. Mutation patterns were similar among groups. The most common V(H)3 gene, V(H)3-23, was utilized less frequently among viremic HIV-1-infected patients (p = 0.03), and overall, mutation frequencies were decreased in nearly all V(H)3 genes compared with controls. Conclusions: B cells from HIV-1-infected patients show decreased mutation frequencies, especially in antigen-binding V(H)3 CDR genes, and selective defects in gene utilization. Similar mutation patterns suggest defects in the quantity, but not quality, of mutator activity. Lower levels of SHM in IgG class-switched B cells from HIV-1-infected patients may contribute to the increased risk of opportunistic infections and impaired humoral responses to preventative vaccines. C1 [Bowers, Elisabeth; MaWhinney, Samantha; Keays, Kathryne M.; Janoff, Edward N.] Univ Colorado Denver, Mucosal & Vaccine Res Program Colorado MAVRC, Aurora, CO 80045 USA. [Bowers, Elisabeth; Keays, Kathryne M.; Janoff, Edward N.] Univ Colorado Denver, Div Infect Dis, Aurora, CO USA. [Bowers, Elisabeth; Janoff, Edward N.] Univ Colorado Denver, Dept Microbiol, Aurora, CO USA. [MaWhinney, Samantha] Univ Colorado Denver, Colorado Sch Publ Hlth, Aurora, CO USA. [Bowers, Elisabeth; Janoff, Edward N.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Scamurra, Ronald W.; Asrani, Anil; Thurn, Joseph R.] Univ Minnesota, Minneapolis VA Hlth Care Syst, Minneapolis, MN USA. [Beniguel, Lydie] Univ St Etienne, Fac Med, GIMAP EA 3064, Saint Etienne, France. RP Janoff, EN (reprint author), Univ Colorado Denver, Mucosal & Vaccine Res Program Colorado MAVRC, Aurora, CO 80045 USA. EM Edward.Janoff@ucdenver.edu FU Veterans Affairs Research Service; University of Colorado Denver Mucosal and Vaccine Research Program Colorado (MAVRC); Colorado Center for AIDS Research Grant [P30 AI054907]; University of Colorado Cancer Center [P30CA046934]; Conseil Regional Rhone-Alpes; National Institutes of Health (NIH) [F32DE005703-01, RO1A10495752-01] FX This work has been supported by the Veterans Affairs Research Service and the University of Colorado Denver Mucosal and Vaccine Research Program Colorado (MAVRC) (ENJ) and facilitated by the infrastructure and resources provided by the Colorado Center for AIDS Research Grant (P30 AI054907), the University of Colorado Cancer Center Core Sequencing Facility (P30CA046934), a grant from "Conseil Regional Rhone-Alpes'' (Recontres Regionales de la Recherche) (LB) and National Institutes of Health (NIH) grants F32DE005703-01 and RO1A10495752-01 (RWS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 7 Z9 7 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 JAN 7 PY 2014 VL 9 IS 1 AR e81913 DI 10.1371/journal.pone.0081913 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 286JC UT WOS:000329463500002 PM 24409278 ER PT J AU Liao, JQ Qian, F Tchabo, N Mhawech-Fauceglia, P Beck, A Qian, ZK Wang, XH Huss, WJ Lele, SB Morrison, CD Odunsi, K AF Liao, Jianqun Qian, Feng Tchabo, Nana Mhawech-Fauceglia, Paulette Beck, Amy Qian, Zikun Wang, Xinhui Huss, Wendy J. Lele, Shashikant B. Morrison, Carl D. Odunsi, Kunle TI Ovarian Cancer Spheroid Cells with Stem Cell-Like Properties Contribute to Tumor Generation, Metastasis and Chemotherapy Resistance through Hypoxia-Resistant Metabolism SO PLOS ONE LA English DT Article ID CARCINOMA ASCITES SPHEROIDS; IN-VITRO MODEL; PROSTATE-CANCER; PROSPECTIVE IDENTIFICATION; INITIATING CELLS; PROGENITOR CELLS; MASS ISOTOPOMER; GENE-EXPRESSION; INVASION; GROWTH AB Cells with sphere forming capacity, spheroid cells, are present in the malignant ascites of patients with epithelial ovarian cancer (EOC) and represent a significant impediment to efficacious treatment due to their putative role in progression, metastasis and chemotherapy resistance. The exact mechanisms that underlie EOC metastasis and drug resistance are not clear. Understanding the biology of sphere forming cells may contribute to the identification of novel therapeutic opportunities for metastatic EOC. Here we generated spheroid cells from human ovarian cancer cell lines and primary ovarian cancer. Xenoengraftment of as few as 2000 dissociated spheroid cells into immune-deficient mice allowed full recapitulation of the original tumor, whereas > 10(5) parent tumor cells remained non-tumorigenic. The spheroid cells were found to be enriched for cells with cancer stem cell-like characteristics such as upregulation of stem cell genes, self-renewal, high proliferative and differentiation potential, and high aldehyde dehydrogenase (ALDH) activity. Furthermore, spheroid cells were more aggressive in growth, migration, invasion, scratch recovery, clonogenic survival, anchorage-independent growth, and more resistant to chemotherapy in vitro. C-13-glucose metabolic studies revealed that spheroid cells route glucose predominantly to anaerobic glycolysis and pentose cycle to the detriment of re-routing glucose for anabolic purposes. These metabolic properties of sphere forming cells appear to confer increased resistance to apoptosis and contribute to more aggressive tumor growth. Collectively, we demonstrated that spheroid cells with cancer stem cell-like characteristics contributed to tumor generation, progression and chemotherapy resistance. This study provides insight into the relationship between tumor dissemination and metabolic attributes of human cancer stem cells and has clinical implications for cancer therapy. C1 [Liao, Jianqun; Lele, Shashikant B.; Odunsi, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA. [Qian, Feng; Odunsi, Kunle] Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA. [Qian, Feng; Beck, Amy; Wang, Xinhui; Odunsi, Kunle] Roswell Pk Canc Inst, Ctr Immunotherapy, Buffalo, NY 14263 USA. [Liao, Jianqun] Roswell Pk Canc Inst, Dept Surg Oncol, Buffalo, NY 14263 USA. [Huss, Wendy J.] Roswell Pk Canc Inst, Dept Urol Oncol, Buffalo, NY 14263 USA. [Huss, Wendy J.] Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA. [Mhawech-Fauceglia, Paulette; Morrison, Carl D.] Roswell Pk Canc Inst, Dept Pathol, Buffalo, NY 14263 USA. [Wang, Xinhui] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg Oncol, Boston, MA USA. [Tchabo, Nana] Womens Canc Ctr, Atlant Hlth Syst Morristown Overlook Med Ctr, Morristown, NJ USA. Womens Canc Ctr, Atlant Hlth Syst Morristown Overlook Med Ctr, Summit, NJ USA. RP Odunsi, K (reprint author), Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA. EM kunle.odunsi@roswellpark.org FU Cancer Research Institute Ovarian Cancer; Cancer Vaccine Collaborative Grant of the Cancer Research Institute; Ludwig Institute for Cancer Research; Anna-Maria Kellen Clinical Investigator Award of the Cancer Research Institute; Roswell Park Cancer Institute Alliance Foundation [NIH P30 CA016056, NIH R01CA158318-01A1]; RPCI-UPCI Ovarian Cancer [SPORE P50CA159981-01A1] FX This work was supported in part by Cancer Research Institute Ovarian Cancer Working Group Grant, Cancer Vaccine Collaborative Grant of the Cancer Research Institute and Ludwig Institute for Cancer Research, Anna-Maria Kellen Clinical Investigator Award of the Cancer Research Institute (to KO), Roswell Park Cancer Institute Alliance Foundation, NIH P30 CA016056; NIH R01CA158318-01A1 and RPCI-UPCI Ovarian Cancer SPORE P50CA159981-01A1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 59 TC 64 Z9 67 U1 3 U2 30 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 7 PY 2014 VL 9 IS 1 AR e84941 DI 10.1371/journal.pone.0084941 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 286JC UT WOS:000329463500038 PM 24409314 ER PT J AU Li, Y Lu, SHJ Tsai, CJ Bohm, C Qamar, S Dodd, RB Meadows, W Jeon, A McLeod, A Chen, FS Arimon, M Berezovska, O Hyman, BT Tomita, T Iwatsubo, T Johnson, CM Farrer, LA Schmitt-Ulms, G Fraser, PE St George-Hyslop, PH AF Li, Yi Lu, Stephen Hsueh-Jeng Tsai, Ching-Ju Bohm, Christopher Qamar, Seema Dodd, Roger B. Meadows, William Jeon, Amy McLeod, Adam Chen, Fusheng Arimon, Muriel Berezovska, Oksana Hyman, Bradley T. Tomita, Taisuke Iwatsubo, Takeshi Johnson, Christopher M. Farrer, Lindsay A. Schmitt-Ulms, Gerold Fraser, Paul E. St George-Hyslop, Peter H. TI Structural Interactions between Inhibitor and Substrate Docking Sites Give Insight into Mechanisms of Human PS1 Complexes SO STRUCTURE LA English DT Article ID FAMILIAL ALZHEIMERS-DISEASE; GAMMA-SECRETASE MODULATORS; ELECTRON-MICROSCOPY; 3-DIMENSIONAL STRUCTURE; TRANSMEMBRANE DOMAIN; MISSENSE MUTATIONS; BETA-APP; PRESENILIN-1; PROTEIN; RECONSTRUCTION AB Presenilin-mediated endoproteolysis of transmembrane proteins plays a key role in physiological signaling and in the pathogenesis of Alzheimer disease and some cancers. Numerous inhibitors have been found via library screens, but their structural mechanisms remain unknown. We used several biophysical techniques to investigate the structure of human presenilin complexes and the effects of peptidomimetic gamma-secretase inhibitors. The complexes are bibbed. The head contains nicastrin ectodomain. The membrane-embedded base has a central channel and a lateral cleft, which may represent the initial substrate docking site. Inhibitor binding induces widespread structural changes, including rotation of the head and closure of the lateral cleft. These changes block substrate access to the catalytic pocket and inhibit the enzyme. Intriguingly, peptide substrate docking has reciprocal effects on the inhibitor binding site. Similar reciprocal shifts may underlie the mechanisms of other inhibitors and of the "lateral gate" through which substrates access to the catalytic site. C1 [Li, Yi; Lu, Stephen Hsueh-Jeng; Tsai, Ching-Ju; Qamar, Seema; Dodd, Roger B.; Meadows, William; St George-Hyslop, Peter H.] Univ Cambridge, Cambridge Inst Med Res, Dept Clin Neurosci, Cambridge CB2 0XY, England. [Bohm, Christopher; Jeon, Amy; McLeod, Adam; Chen, Fusheng; Schmitt-Ulms, Gerold; Fraser, Paul E.; St George-Hyslop, Peter H.] Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON M5S 3H2, Canada. [Bohm, Christopher; Jeon, Amy; McLeod, Adam; Chen, Fusheng; Schmitt-Ulms, Gerold; Fraser, Paul E.; St George-Hyslop, Peter H.] Univ Toronto, Dept Med, Toronto, ON M5S 3H2, Canada. [Bohm, Christopher; Jeon, Amy; McLeod, Adam; Chen, Fusheng; Schmitt-Ulms, Gerold; Fraser, Paul E.; St George-Hyslop, Peter H.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 3H2, Canada. [Bohm, Christopher; Jeon, Amy; McLeod, Adam; Chen, Fusheng; Schmitt-Ulms, Gerold; Fraser, Paul E.; St George-Hyslop, Peter H.] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 3H2, Canada. [Arimon, Muriel; Berezovska, Oksana; Hyman, Bradley T.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Alzheimer Res Unit, Charlestown, MA 02129 USA. [Tomita, Taisuke; Iwatsubo, Takeshi] Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Neuropathol & Neurosci, Tokyo 1130033, Japan. [Tomita, Taisuke; Iwatsubo, Takeshi] Univ Tokyo, Grad Sch Med, Dept Neuropathol, Tokyo 1130033, Japan. [Tomita, Taisuke; Iwatsubo, Takeshi] Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Bunkyo Ku, Tokyo 1130033, Japan. [Johnson, Christopher M.] MRC, Mol Biol Lab, Cambridge CB2 0QH, England. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Med Biomed Genet, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA. RP St George-Hyslop, PH (reprint author), Univ Cambridge, Cambridge Inst Med Res, Dept Clin Neurosci, Cambridge CB2 0XY, England. EM phs22@cam.ac.uk RI Arimon, Muriel/I-4054-2015; OI Arimon, Muriel/0000-0002-0894-3324; Farrer, Lindsay/0000-0001-5533-4225; Tomita, Taisuke/0000-0002-0075-5943 FU Wellcome Trust; Medical Research Council; National Institutes of Health Research; National Institutes of Health [NIH AG15379]; Japan Society for the Promotion of Science; Core Research for Evolutional Science and Technology of Japan Science and Technology Agency; Alzheimer Society of Ontario; Canadian Institutes of Health Research FX We thank K.R. Vinoth Kumar, Xiaochen Bai, and Richard Henderson from the MRC Laboratory of Molecular Biology for help and advice with this work. We thank Satoko Osawa from the University of Tokyo for technical assistance and Dr. Haruhiko Fuwa of Tohoku University for the compounds. This work was supported by grants from the Wellcome Trust, the Medical Research Council, the National Institutes of Health Research (to P.H.St G.-H.), the National Institutes of Health (NIH AG15379 to O.B. and B.T.H.), the Japan Society for the Promotion of Science (grants-in-aid for Young Scientists to T.T.), the Core Research for Evolutional Science and Technology of Japan Science and Technology Agency (to T.T. and TI.), the Alzheimer Society of Ontario, and the Canadian Institutes of Health Research (to P.H.St G.-H., G.S.-U., and P.E.F.). NR 49 TC 22 Z9 22 U1 3 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 EI 1878-4186 J9 STRUCTURE JI Structure PD JAN 7 PY 2014 VL 22 IS 1 BP 125 EP 135 DI 10.1016/j.str.2013.09.018 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 288DU UT WOS:000329593000014 PM 24210759 ER PT J AU Roberts, LD Bostrom, P O'Sullivan, JF Schinzel, RT Lewis, GD Dejam, A Lee, YK Palma, MJ Calhoun, S Georgiadi, A Chen, MH Ramachandran, VS Larson, MG Bouchard, C Rankinen, T Souza, AL Clish, CB Wang, TJ Estall, JL Soukas, AA Cowan, CA Spiegelman, BM Gerszten, RE AF Roberts, Lee D. Bostrom, Pontus O'Sullivan, John F. Schinzel, Robert T. Lewis, Gregory D. Dejam, Andre Lee, Youn-Kyoung Palma, Melinda J. Calhoun, Sondra Georgiadi, Anastasia Chen, Ming-Huei Ramachandran, Vasan S. Larson, Martin G. Bouchard, Claude Rankinen, Tuomo Souza, Amanda L. Clish, Clary B. Wang, Thomas J. Estall, Jennifer L. Soukas, Alexander A. Cowan, Chad A. Spiegelman, Bruce M. Gerszten, Robert E. TI beta-Aminoisobutyric Acid Induces Browning of White Fat and Hepatic beta-Oxidation and Is Inversely Correlated with Cardiometabolic Risk Factors SO CELL METABOLISM LA English DT Article ID MITOCHONDRIAL UNCOUPLING PROTEIN; GENOME-WIDE ASSOCIATION; SKELETAL-MUSCLE; ADIPOSE-TISSUE; INSULIN-RESISTANCE; COACTIVATOR PGC-1; GENE-EXPRESSION; LIVER-DISEASE; PPAR-ALPHA; IN-VIVO AB The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) regulates metabolic genes in skeletal muscle and contributes to the response of muscle to exercise. Muscle PGC-1 alpha transgenic expression and exercise both increase the expression of thermogenic genes within white adipose. How the PGC-1 alpha-mediated response to exercise in muscle conveys signals to other tissues remains incompletely defined. We employed a metabolomic approach to examine metabolites secreted from myocytes with forced expression of PGC-1 alpha, and identified beta-aminoisobutyric acid (BAIBA) as a small molecule myokine. BAIBA increases the expression of brown adipocyte-specific genes in white adipocytes and beta-oxidation in hepatocytes both in vitro and in vivo through a PPAR alpha-mediated mechanism, induces a brown adipose-like phenotype in human pluripotent stem cells, and improves glucose homeostasis in mice. In humans, plasma BAIBA concentrations are increased with exercise and inversely associated with metabolic risk factors. BAIBA may thus contribute to exercise-induced protection from metabolic diseases. C1 [Roberts, Lee D.; O'Sullivan, John F.; Schinzel, Robert T.; Lewis, Gregory D.; Dejam, Andre; Lee, Youn-Kyoung; Palma, Melinda J.; Wang, Thomas J.; Cowan, Chad A.; Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Bostrom, Pontus; Calhoun, Sondra; Spiegelman, Bruce M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bostrom, Pontus; Calhoun, Sondra; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bostrom, Pontus; Georgiadi, Anastasia] Karolinska Inst, Inst Cell Och Mol Biol CMB, S-17177 Stockholm, Sweden. [Schinzel, Robert T.; Lee, Youn-Kyoung; Cowan, Chad A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Schinzel, Robert T.; Lee, Youn-Kyoung; Cowan, Chad A.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Schinzel, Robert T.] Free Univ Berlin, Fachbereich Biol, Inst Biotechnol Mikrobiol, D-14195 Berlin, Germany. [Lewis, Gregory D.; Wang, Thomas J.; Cowan, Chad A.; Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [Lewis, Gregory D.; Souza, Amanda L.; Clish, Clary B.; Gerszten, Robert E.] Broad Inst & Harvard, Cambridge, MA 02142 USA. [Chen, Ming-Huei; Ramachandran, Vasan S.; Larson, Martin G.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Chen, Ming-Huei; Ramachandran, Vasan S.; Larson, Martin G.] Boston Univ, Sch Med, Framingham, MA 01702 USA. [Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Chen, Ming-Huei] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Ramachandran, Vasan S.] Boston Univ, Sch Med, Boston Med Ctr, Cardiol Sect, Boston, MA 02118 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Bouchard, Claude; Rankinen, Tuomo] Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Wang, Thomas J.] Vanderbilt Univ, Div Cardiol, Nashville, TN 37232 USA. [Estall, Jennifer L.] Inst Rech Clin Montreal, Montreal, PQ H2W 1R7, Canada. [Soukas, Alexander A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA. RP Gerszten, RE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM rgerszten@partners.org RI Bouchard, Claude/A-7637-2009; OI Ramachandran, Vasan/0000-0001-7357-5970; Roberts, Lee/0000-0002-1455-5248 FU NIH [R01 DK081572, R01 HL098280, DK 31405]; Leducq Foundation; American Heart Association; NIH/NHLBI [N01-HC-25195]; Leducq Foundation Career Development Award; Wenner-Gren Foundation; Swedish Heart and Lung Foundation; John W. Barton Sr. Chair in Genetics and Nutrition; [NIH-RO1-HL045670] FX This work was supported by NIH R01 DK081572, NIH R01 HL098280, the Leducq Foundation, and the American Heart Association (R.E.G.) and by NIH DK 31405 (B.M.S.). The Framingham Heart Study is supported by NIH/NHLBI N01-HC-25195. L.D.R. is supported by a Leducq Foundation Career Development Award. P.B. is supported by the Wenner-Gren Foundation and the Swedish Heart and Lung Foundation. The HERITAGE Family Study is supported by NIH-RO1-HL045670. C.B. is supported by the John W. Barton Sr. Chair in Genetics and Nutrition. NR 56 TC 103 Z9 105 U1 5 U2 36 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD JAN 7 PY 2014 VL 19 IS 1 BP 96 EP 108 DI 10.1016/j.cmet.2013.12.003 PG 13 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 285YO UT WOS:000329431200012 PM 24411942 ER PT J AU Mor, MK Sevick, MA Shields, AM Green, JA Palevsky, PM Arnold, RM Fine, MJ Weisbord, SD AF Mor, Maria K. Sevick, Mary Ann Shields, Anne Marie Green, Jamie A. Palevsky, Paul M. Arnold, Robert M. Fine, Michael J. Weisbord, Steven D. TI Sexual Function, Activity, and Satisfaction among Women Receiving Maintenance Hemodialysis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID QUALITY-OF-LIFE; STAGE RENAL-DISEASE; SYMPTOM MANAGEMENT STRATEGIES; ERECTILE DYSFUNCTION; SILDENAFIL TREATMENT; PERITONEAL-DIALYSIS; FUNCTION INDEX; DEPRESSION; PAIN; PREVALENCE AB Background and objectivesPast studies that demonstrated that sexual dysfunction is common among women receiving chronic hemodialysis did not distinguish sexual dysfunction/difficulty from sexual inactivity. This study sought to differentiate these in order to elucidate the prevalence of true sexual dysfunction in this population.Design, setting, participants, & measurementsAs part of a clinical trial of symptom management strategies in patients receiving chronic hemodialysis, female sexual function was prospectively assessed monthly for 6 months and quarterly thereafter using the Female Sexual Function Index, to which questions were added differentiating sexual dysfunction/difficulty from sexual inactivity. Beginning in month 7, patients were asked three questions about sexual activity, difficulty, and satisfaction monthly.ResultsOf the women enrolled in the clinical trial,125 participants completed 1721 assessments between 2009 and 2011. Scores on 574 of 643 (89%) quarterly Female Sexual Function Index assessments were consistent with sexual dysfunction, due largely to sexual inactivity, which was reported on 525 (82%) quarterly assessments. When reported (n=1663), the most frequently described reasons for sexual inactivity were lack of interest in sex (n=715; 43%) and lack of a partner (n=647; 39%), but rarely sexual difficulty (n=36; 2%). When reported (n=1582), women were moderately to very satisfied with their sexual life on 1020 (64%) assessments and on 513 of 671 (76%) assessments in which lack of interest was cited as a reason for sexual inactivity. Women indicated an interest in learning about the causes of and treatment for sexual dysfunction on just 5% of all assessments.ConclusionsAlthough many women receiving chronic hemodialysis are sexually inactive, few describe sexual difficulty. Most, including those with a lack of interest in sex, are satisfied with their sexual life and few wish to learn about treatment options. These findings suggest that true sexual dysfunction is uncommon in this population and that treatment opportunities are rare. C1 [Mor, Maria K.; Shields, Anne Marie; Fine, Michael J.; Weisbord, Steven D.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Sevick, Mary Ann] NYU, Sch Med, Dept Populat Hlth, New York, NY USA. [Green, Jamie A.] Geisinger Med Ctr, Dept Nephrol, Danville, PA 17822 USA. [Palevsky, Paul M.; Weisbord, Steven D.] Vet Affairs Pittsburgh Healthcare Syst, Med Serv Line, Renal Sect, Pittsburgh, PA 15240 USA. [Palevsky, Paul M.; Weisbord, Steven D.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. [Arnold, Robert M.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Arnold, Robert M.] Univ Pittsburgh, Sch Med, Div Palliat Care, Pittsburgh, PA USA. RP Weisbord, SD (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Med Serv Line, Renal Sect, 7E Room 120,111F-U, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu FU Department of Veterans Affairs Health Services Research and Development Merit Review award [IIR 07-190] FX This work was supported by a Department of Veterans Affairs Health Services Research and Development Merit Review award (IIR 07-190). NR 31 TC 9 Z9 9 U1 1 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JAN 7 PY 2014 VL 9 IS 1 BP 128 EP 134 DI 10.2215/CJN.05470513 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 285AL UT WOS:000329364700018 PM 24357510 ER PT J AU Frey, K Bauer, J Unholtz, D Kurz, C Kramer, M Bortfeld, T Parodi, K AF Frey, K. Bauer, J. Unholtz, D. Kurz, C. Kraemer, M. Bortfeld, T. Parodi, K. TI TPSPET-A TPS-based approach for in vivo dose verification with PET in proton therapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID MONTE-CARLO SIMULATIONS; BEAM RANGE VERIFICATION; SCANNED PROTON; PLASTIC PHANTOMS; ION THERAPY; RADIOTHERAPY; UNCERTAINTIES; DISTRIBUTIONS; IRRADIATION; MODEL AB Since the interest in ion-irradiation for tumour therapy has significantly increased over the last few decades, intensive investigations are performed to improve the accuracy of this form of patient treatment. One major goal is the development of methods for in vivo dose verification. In proton therapy, a PET (positron emission tomography)-based approach measuring the irradiation-induced tissue activation inside the patient has been already clinically implemented. The acquired PET images can be compared to an expectation, derived under the assumption of a correct treatment application, to validate the particle range and the lateral field position in vivo. In the context of this work, TPSPET is introduced as a new approach to predict proton-irradiation induced three-dimensional positron emitter distributions by means of the same algorithms of the clinical treatment planning system (TPS). In order to perform additional activity calculations, reaction-channel-dependent input positron emitter depth distributions are necessary, which are determined from the application of a modified filtering approach to the TPS reference depth dose profiles in water. This paper presents the implementation of TPSPET on the basis of the research treatment planning software treatment planning for particles. The results are validated in phantom and patient studies against Monte Carlo simulations, and compared to beta(+)-emitter distributions obtained from a slightly modified version of the originally proposed one-dimensional filtering approach applied to three-dimensional dose distributions. In contrast to previously introduced methods, TPSPET provides a faster implementation, the results show no sensitivity to lateral field extension and the predicted beta(+)-emitter densities are fully consistent to the planned treatment dose as they are calculated by the same pencil beam algorithms. These findings suggest a large potential of the application of TPSPET for in vivo dose verification in the daily clinical routine. C1 [Frey, K.; Parodi, K.] Univ Munich, Munich, Germany. [Frey, K.; Bauer, J.; Unholtz, D.; Kurz, C.; Parodi, K.] Heidelberg Ion Beam Therapy Ctr, Heidelberg, Germany. [Bauer, J.; Unholtz, D.; Kurz, C.; Parodi, K.] Univ Clin, Dept Radiat Oncol, Heidelberg, Germany. [Kraemer, M.] GSI Helmholtzzentrum Schwerionenforsch, Darmstadt, Germany. [Bortfeld, T.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Frey, K (reprint author), Univ Munich, Munich, Germany. EM K.Frey@physik.uni-muenchen.de NR 22 TC 7 Z9 7 U1 0 U2 3 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 JAN 6 PY 2014 VL 59 IS 1 BP 1 EP 21 DI 10.1088/0031-9155/59/1/1 PG 21 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA AN8FT UT WOS:000340839500001 PM 24323977 ER PT J AU Gross, R Bellamy, SL Chapman, J Han, XY O'Duor, J Strom, BL Houts, PS Palmer, SC Coyne, JC AF Gross, Robert Bellamy, Scarlett L. Chapman, Jennifer Han, Xiaoyan O'Duor, Jacqueline Strom, Brian L. Houts, Peter S. Palmer, Steven C. Coyne, James C. TI The Effects of a Problem Solving-Based Intervention on Depressive Symptoms and HIV Medication Adherence Are Independent SO PLOS ONE LA English DT Article ID ANTIRETROVIRAL THERAPY; ANTIDEPRESSANT TREATMENT; CANCER-PATIENTS; DISORDERS; RISK; METAANALYSIS; HIV/AIDS; PROJECT; ANXIETY; TRIAL AB Depression and depressive symptoms predict poor adherence to medical therapy, but the association is complex, nonspecific, and difficult to interpret. Understanding this association may help to identify the mechanism explaining the results of interventions that improve both medical therapy adherence and depressive symptoms as well as determine the importance of targeting depression in adherence interventions. We previously demonstrated that Managed Problem Solving (MAPS) focused on HIV medication adherence improved adherence and viral load in patients initiating a new antiretroviral regimen. Here, we assessed whether MAPS improved depressive symptoms and in turn, whether changes in depressive symptoms mediated changes in adherence and treatment outcomes. We compared MAPS to usual care with respect to presence of depressive symptoms during the trial using logistic regression. We then assessed whether MAPS' effect on depressive symptoms mediated the relationship between MAPS and adherence and virologic outcomes using linear and logistic regression, respectively. Mediation was defined by the disappearance of the mathematical association between MAPS and the outcomes when the proposed mediator was included in regression models. Although MAPS participants had a lower rate of depressive symptoms (OR = 0.45, 95% confidence interval 0.21-0.93), there was no evidence of mediation of the effects of MAPS on adherence and virological outcome by improvements in depression. Thus, interventions for medication adherence may not need to address depressive symptoms in order to impact both adherence and depression; this remains to be confirmed, however, in other data. C1 [Gross, Robert; Bellamy, Scarlett L.; Chapman, Jennifer; Han, Xiaoyan; O'Duor, Jacqueline; Strom, Brian L.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Gross, Robert; Bellamy, Scarlett L.; Chapman, Jennifer; Han, Xiaoyan; O'Duor, Jacqueline; Strom, Brian L.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Gross, Robert; Strom, Brian L.] Univ Penn, Perelman Sch Med, Ctr Pharmacoepidemiol Res & Training, Philadelphia, PA 19104 USA. [Gross, Robert] Univ Penn, Perelman Sch Med, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. [Gross, Robert] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Houts, Peter S.] Penn State Univ, Coll Med, Hershey, PA USA. [Palmer, Steven C.; Coyne, James C.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Coyne, James C.] Univ Groningen, Univ Med Ctr Groningen, Dept Hlth Sci, Hlth Psychol Sect, Groningen, Netherlands. RP Gross, R (reprint author), Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. EM grossr@mail.med.upenn.edu FU National Institute Of Mental Health [R01 MH080701, R01 MH067498]; National Center for Research Resources [UL1 RR024134]; National Institute of Allergy and Infectious Diseases; Penn Center for AIDS Research [P30 AI045008]; Philadelphia Veterans Affairs Medical Center; Bristol-Myers Squibb; Abbott Laboratories FX Research reported in this publication was supported by the National Institute Of Mental Health under Award Numbers R01 MH080701 and R01 MH067498, by the National Center for Research Resources under Award Number UL1 RR024134, by the National Institute of Allergy and Infectious Diseases via core services and support from the Penn Center for AIDS Research under Award Number P30 AI045008 and career support (RG) from the Philadelphia Veterans Affairs Medical Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. During the course of this study, Dr. Gross received research support via contracts with Bristol-Myers Squibb and Abbott Laboratories for work related to HIV and its treatment, but not for work on this study. Dr. Strom was supported in part by contracts with and received payment for consulting with numerous pharmaceutical companies, none of which was related to HIV or this study. NR 26 TC 4 Z9 4 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 6 PY 2014 VL 9 IS 1 AR e84952 DI 10.1371/journal.pone.0084952 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 286IW UT WOS:000329462700058 PM 24400124 ER PT J AU Lei, NY Jabaji, Z Wang, JF Joshi, VS Brinkley, GJ Khalil, H Wang, FC Jaroszewicz, A Pellegrini, M Li, LH Lewis, M Stelzner, M Dunn, JCY Martin, MG AF Lei, Nan Ye Jabaji, Ziyad Wang, Jiafang Joshi, Vaidehi S. Brinkley, Garrett J. Khalil, Hassan Wang, Fengchao Jaroszewicz, Artur Pellegrini, Matteo Li, Linheng Lewis, Michael Stelzner, Matthias Dunn, James C. Y. Martin, G. Martin TI Intestinal Subepithelial Myofibroblasts Support the Growth of Intestinal Epithelial Stem Cells SO PLOS ONE LA English DT Article ID IN-VITRO; WNT/BETA-CATENIN; SELF-RENEWAL; NICHE; LGR5; CRYPT; DIFFERENTIATION; TRANSPLANTATION; RECEPTORS; PITFALLS AB Intestinal epithelial stem cells (ISCs) are the focus of recent intense study. Current in vitro models rely on supplementation with the Wnt agonist R-spondin1 to support robust growth, ISC self-renewal, and differentiation. Intestinal subepithelial myofibroblasts (ISEMFs) are important supportive cells within the ISC niche. We hypothesized that co-culture with ISEMF enhances the growth of ISCs in vitro and allows for their successful in vivo implantation and engraftment. ISC-containing small intestinal crypts, FACS-sorted single ISCs, and ISEMFs were procured from C57BL/6 mice. Crypts and single ISCs were grown in vitro into enteroids, in the presence or absence of ISEMFs. ISEMFs enhanced the growth of intestinal epithelium in vitro in a proximity-dependent fashion, with co-cultures giving rise to larger enteroids than monocultures. Co-culture of ISCs with supportive ISEMFs relinquished the requirement of exogenous R-spondin1 to sustain long-term growth and differentiation of ISCs. Mono-and co-cultures were implanted subcutaneously in syngeneic mice. Co-culture with ISEMFs proved necessary for successful in vivo engraftment and proliferation of enteroids; implants without ISEMFs did not survive. ISEMF whole transcriptome sequencing and qPCR demonstrated high expression of specific R-spondins, well-described Wnt agonists that supports ISC growth. Specific non-supportive ISEMF populations had reduced expression of R-spondins. The addition of ISEMFs in intestinal epithelial culture therefore recapitulates a critical element of the intestinal stem cell niche and allows for its experimental interrogation and biodesign-driven manipulation. C1 [Lei, Nan Ye; Joshi, Vaidehi S.; Dunn, James C. Y.] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA USA. [Lei, Nan Ye; Jabaji, Ziyad; Khalil, Hassan; Stelzner, Matthias; Dunn, James C. Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Wang, Jiafang; Brinkley, Garrett J.; Martin, G. Martin] Univ Calif Los Angeles, Mattel Childrens Hosp, Dept Pediat, Div Gastroenterol & Nutr, Los Angeles, CA 90095 USA. [Wang, Jiafang; Brinkley, Garrett J.; Martin, G. Martin] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Wang, Fengchao; Li, Linheng] Stowers Inst Med Res, Kansas City, MO USA. [Jaroszewicz, Artur; Pellegrini, Matteo] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA USA. [Li, Linheng] Univ Kansas, Med Ctr, Dept Pathol, Kansas City, KS 66103 USA. [Li, Linheng] Univ Kansas, Med Ctr, Lab Med, Kansas City, KS 66103 USA. [Lewis, Michael] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol, Los Angeles, CA USA. [Stelzner, Matthias] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. RP Martin, MG (reprint author), Univ Calif Los Angeles, Mattel Childrens Hosp, Dept Pediat, Div Gastroenterol & Nutr, Los Angeles, CA 90095 USA. EM mmartin@mednet.ucla.edu OI Khalil, Hassan/0000-0002-3835-1290 FU National Institute of Diabetes and Digestive and Kidney Diseases U01 Intestinal Stem Cell Consortium [DK085535-01, DK085535-02S2, DK083762, DK083319]; California Institute for Regenerative Medicine [RT2-01985] FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases U01 Intestinal Stem Cell Consortium (DK085535-01 and DK085535-02S2), DK083762, DK083319 and the California Institute for Regenerative Medicine (RT2-01985). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 18 Z9 20 U1 1 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 e84651 DI 10.1371/journal.pone.0084651 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 286IW UT WOS:000329462700040 PM 24400106 ER PT J AU Sassoubre, LM Ramsey, MM Gilmore, MS Boehm, AB AF Sassoubre, Lauren M. Ramsey, Matthew M. Gilmore, Michael S. Boehm, Alexandria B. TI Transcriptional response of Enterococcus faecalis to sunlight SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article DE Enterococcus; Photoinactivation; Gene expression; Sunlight; Oxidative stress ID OXIDATIVE STRESS-RESPONSE; PROBE LEVEL DATA; ESCHERICHIA-COLI; GENE-EXPRESSION; QUANTITATIVE PCR; SALMONELLA-TYPHIMURIUM; WATER-QUALITY; PROTEINS; INACTIVATION; OXYGEN AB Microarrays were used to investigate the transcriptional response of Enterococcus faecalis to photostress. E. faecalis are Gram-positive bacteria used as indicators of water quality and have been shown to vary diurnally in response to sunlight. E. faecalis in filtered seawater microcosms were exposed to artificial sunlight for 12 h and then placed in the dark for 12 h. Transcript abundance was measured at 0, 2, 6, 12, and 24 h in the sunlit microcosm and a dark control using microarrays. Culturable E. faecalis concentrations decreased 6-7 orders of magnitude within the first 6 h of light exposure. After 12 h in the dark, no evidence of dark-repair was observed. Expression data collected after 12 h of sunlight exposure revealed a difference in transcript abundance in the light relative to dark microcosms for 35 unique ORFs, 33 ORFs showed increased transcript abundance and 2 ORFs showed reduced transcript abundance. A majority (51%) of the ORFs with increased transcript abundance in the sunlit relative to dark microcosms encoded hypothetical proteins; others were associated with protein synthesis, oxidative stress and DNA repair. Results suggest that E. faecalis exposed to sunlight actively transcribe RNA in response to photostress. (C) 2013 Elsevier B.V. All rights reserved. C1 [Sassoubre, Lauren M.; Boehm, Alexandria B.] Stanford Univ, Dept Civil & Environm Engn, Stanford, CA 94305 USA. [Ramsey, Matthew M.; Gilmore, Michael S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Dept Microbiol, Boston, MA USA. [Ramsey, Matthew M.; Gilmore, Michael S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Immunobiol, Boston, MA USA. RP Boehm, AB (reprint author), Stanford Univ, Dept Civil & Environm Engn, 473 Via Ortega,Mail Code 4020, Stanford, CA 94305 USA. EM aboehm@stanford.edu FU NSF [OCE-1129270]; NIH/NIAID [AI083214, AI072360] FX This project was funded by NSF OCE-1129270 as well as NIH/NIAID Grants AI083214 (Harvard-wide Program on Antibiotic Resistance) and AI072360. We thank two anonymous reviewers that provided helpful comments that improved the manuscript. NR 59 TC 2 Z9 2 U1 1 U2 9 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD JAN 5 PY 2014 VL 130 BP 349 EP 356 DI 10.1016/j.jphotobiol.2013.12.013 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AD1NC UT WOS:000332999700044 PM 24434819 ER PT J AU Bhatt, SP Cole, AG Wells, JM Nath, H Watts, JR Cockcroft, JR Dransfield, MT AF Bhatt, Surya P. Cole, Adam G. Wells, James Michael Nath, Hrudaya Watts, Jubal R. Cockcroft, John R. Dransfield, Mark T. TI Determinants of arterial stiffness in COPD SO BMC PULMONARY MEDICINE LA English DT Article DE COPD; Arterial stiffness; Arterial calcification; Cardiovascular ID OBSTRUCTIVE PULMONARY-DISEASE; CORONARY-HEART-DISEASE; CARDIOVASCULAR RISK; ALL-CAUSE; MORTALITY; EMPHYSEMA; PREDICTION; ATHEROSCLEROSIS; CALCIFICATION; IMPROVEMENT AB Background: Cardiovascular morbidity and mortality is high in patients with chronic obstructive pulmonary disease (COPD) and arterial stiffness is a potentially modifiable risk factor with added predictive value beyond that obtained from traditional risk factors. Arterial stiffness has been the target of pharmacologic and exercise interventions in patients with COPD, but the effects appear limited to those patients with more significant elevations in arterial stiffness. We aimed to identify predictors of increased arterial stiffness in a cohort with moderate to severe COPD. Methods: Aortic pulse wave velocity (aPWV) was measured in subjects with moderate to severe COPD enrolled in a multicenter randomized controlled trial. Subjects were categorized into quartiles based on aPWV values and factors affecting high arterial stiffness were assessed. Multivariate models were created to identify independent predictors of high aPWV, and cardiovascular disease (CVD). Results: 153 patients were included. Mean age was 63.2 (SD 8.2) years and mean FEV1 was 55.4 (SD 15.2) % predicted. Compared to the quartile with the lowest aPWV, subjects in the highest quartile were older, had higher systolic blood pressure (SBP), were more likely to be current smokers, and had greater burden of thoracic aortic calcification. On multivariate analyses, age (adjusted OR 1.14, 95% CI 1.05 to 1.25, p = 0.003) and SBP (adjusted OR 1.06, 95% CI 1.02 to 1.09, p = 0.001) were independent predictors of elevated aPWV. Body mass index, therapy with cholesterol lowering medications and coronary calcification were independent predictors of CVD. Conclusions: Elevated arterial stiffness in patients with COPD can be predicted using age, blood pressure and thoracic aortic calcification. This will help identify subjects for enrollment in clinical trials using aPWV for assessing the impact of COPD therapies on CV outcomes. C1 [Bhatt, Surya P.; Cole, Adam G.; Wells, James Michael; Dransfield, Mark T.] Univ Alabama Birmingham, Lung Hlth Ctr, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. [Nath, Hrudaya; Watts, Jubal R.] Univ Alabama Birmingham, Dept Radiol, Birmingham, AL USA. [Cockcroft, John R.] Univ Wales Hosp, Dept Cardiol, Wales Heart Res Inst, Cardiff CF4 4XW, S Glam, Wales. [Dransfield, Mark T.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Bhatt, SP (reprint author), Univ Alabama Birmingham, Lung Hlth Ctr, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. EM spbhatt@uab.edu OI Watts, Jubal/0000-0002-9006-1637 FU GlaxoSmithKline, Respiratory and Immuno-Inflammation Medicines Development Center, Research Triangle Park, NC, USA FX GlaxoSmithKline, Respiratory and Immuno-Inflammation Medicines Development Center, Research Triangle Park, NC, USA NR 32 TC 9 Z9 9 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2466 J9 BMC PULM MED JI BMC Pulm. Med. PD JAN 4 PY 2014 VL 14 AR 1 DI 10.1186/1471-2466-14-1 PG 7 WC Respiratory System SC Respiratory System GA AB1QE UT WOS:000331567400001 PM 24387157 ER PT J AU Liu, SJ Huang, ZS Wu, QG Huang, ZJ Wu, LR Yan, WL Chang, DL Yang, Z Wang, ZW AF Liu, Sijun Huang, Zhaosheng Wu, Qingguang Huang, Zhangjie Wu, Lirong Yan, Wenli Chang, David Lungpao Yang, Zheng Wang, Zongwei TI Quantization and diagnosis of Shanghuo (Heatiness) in Chinese medicine using a diagnostic scoring scheme and salivary biochemical parameters SO CHINESE MEDICINE LA English DT Article AB Background: This study aims to establish a diagnostic scoring scheme for Shanghuo (Heatiness) and to evaluate whether Shanghuo is associated with biochemical parameters of salivary lysozyme (LYZ), salivary secreted immunoglobulin (S-IgA), salivary amylase (AMS), and saliva flow rate (SFR). Methods: We collected 121 Shanghuo patients at the Affiliated Hospitals of Guangzhou University of Traditional Chinese Medicine in Guangdong Province, 60 cases as a Shanghuo recovered group, and 60 healthy cases as a healthy control group. The diagnostic scoring scheme was established by probability theory and maximum likelihood discriminatory analysis on the basis of epidemiology with the design of self-controlled clinical trial. Subsequently, we used the same methods to collect 120 Shanghuo patients, 60 Shanghuo recovered cases, and 60 healthy cases in both Hunan Province and Henan Province. The levels of LYZ, S-IgA, AMS, and SFR were tested when the patients suffered from Shanghuo or recovered, respectively. Results: The diagnostic score table for Shanghuo syndrome was established first. In the retrospective tests, the sensitivity, specificity, accuracy, and positive likelihood ratio of the diagnostic score table were 98.9%, 93.5%, 97.5%, and 14.34%, respectively. In the prospective tests, the corresponding values were 94.9%, 85.7%, 91.7%, and 6.64%, respectively. Shanghuo was classified into three degrees based on the diagnostic scores, common Shanghuo: 63-120; serious Shanghuo: 121-150; very serious Shanghuo: >150. A negative correlation was found between Shanghuo and S-IgA (R = -0.428; P = 0.000). The level of S-IgA was also affected by seasonal and regional factors. No significant correlations were found between Shanghuo and the levels of LYZ, AMS, and SFR. Conclusions: In this study, Shanghuo could be diagnosed by the combination of the diagnostic score table and S-IgA level. C1 [Liu, Sijun; Huang, Zhaosheng; Wu, Qingguang; Huang, Zhangjie; Wu, Lirong; Yan, Wenli] Guangzhou Univ Tradit Chinese Med, Guangzhou 510405, Guangdong, Peoples R China. [Chang, David Lungpao; Yang, Zheng] Colgate Palmol China Co Ltd, Guangzhou, Guangdong, Peoples R China. [Wang, Zongwei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Huang, ZS (reprint author), Guangzhou Univ Tradit Chinese Med, 12 Jichang Rd, Guangzhou 510405, Guangdong, Peoples R China. EM vip.hzs@gzhtcm.edu.cn; zwang0@partners.org FU National Natural Science Foundation of China [81273817]; Guangdong Province administration of traditional Chinese medicine [20121225]; Colgate-Palmolive (China) Company Ltd. FX This study was supported jointly by a grant from the National Natural Science Foundation of China (No. 81273817) and the program of Guangdong Province administration of traditional Chinese medicine (No. 20121225). The authors are also grateful to Colgate-Palmolive (China) Company Ltd. for funding this study. NR 24 TC 2 Z9 2 U1 1 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1749-8546 J9 CHIN MED-UK JI Chin. Med. PD JAN 4 PY 2014 VL 9 AR 2 DI 10.1186/1749-8546-9-2 PG 10 WC Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Integrative & Complementary Medicine; Pharmacology & Pharmacy GA 302YI UT WOS:000330640700001 PM 24386887 ER PT J AU Fuchs, CS Tomasek, J Yong, CJ Dumitru, F Passalacqua, R Goswami, C Safran, H dos Santos, LV Aprile, G Ferry, DR Melichar, B Tehfe, M Topuzov, E Zalcberg, JR Chau, I Campbell, W Sivanandan, C Pikiel, J Koshiji, M Hsu, YZ Liepa, AM Gao, L Schwartz, JD Tabernero, J AF Fuchs, Charles S. Tomasek, Jiri Yong, Cho Jae Dumitru, Filip Passalacqua, Rodolfo Goswami, Chanchal Safran, Howard dos Santos, Lucas Vieira Aprile, Giuseppe Ferry, David R. Melichar, Bohuslav Tehfe, Mustapha Topuzov, Eldar Zalcberg, John Raymond Chau, Ian Campbell, William Sivanandan, Choondal Pikiel, Joanna Koshiji, Minori Hsu, Yanzhi Liepa, Astra M. Gao, Ling Schwartz, Jonathan D. Tabernero, Josep CA REGARD Trial Investigators TI Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial SO LANCET LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; CLINICOPATHOLOGICAL SIGNIFICANCE; MICROVESSEL DENSITY; TUMOR ANGIOGENESIS; SUPPORTIVE CARE; CLINICAL-TRIALS; FACTOR RECEPTOR; CANCER; EXPRESSION AB Background Vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2)-mediated signalling and angiogenesis can contribute to the pathogenesis and progression of gastric cancer. We aimed to assess whether ramucirumab, a monoclonal antibody VEGFR-2 antagonist, prolonged survival in patients with advanced gastric cancer. Methods We did an international, randomised, double-blind, placebo-controlled, phase 3 trial between Oct 6, 2009, and Jan 26, 2012, at 119 centres in 29 countries in North America, Central and South America, Europe, Asia, Australia, and Africa. Patients aged 24-87 years with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression after first-line platinum-containing or fluoropyrimidine-containing chemotherapy were randomly assigned (2: 1), via a central interactive voice-response system, to receive best supportive care plus either ramucirumab 8 mg/kg or placebo, intravenously once every 2 weeks. The study sponsor, participants, and investigators were masked to treatment assignment. The primary endpoint was overall survival. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00917384. Findings 355 patients were assigned to receive ramucirumab (n=238) or placebo (n=117). Median overall survival was 5.2 months (IQR 2.3-9.9) in patients in the ramucirumab group and 3.8 months (1.7-7.1) in those in the placebo group (hazard ratio [HR] 0.776, 95% CI 0.603-0.998; p=0.047). The survival benefit with ramucirumab remained unchanged after multivariable adjustment for other prognostic factors (multivariable HR 0.774, 0.605-0.991; p=0.042). Rates of hypertension were higher in the ramucirumab group than in the placebo group (38 [16%] vs nine [8%]), whereas rates of other adverse events were mostly similar between groups (223 [94%] vs 101 [88%]). Five (2%) deaths in the ramucirumab group and two (2%) in the placebo group were considered to be related to study drug. Interpretation Ramucirumab is the first biological treatment given as a single drug that has survival benefits in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma progressing after first-line chemotherapy. Our findings validate VEGFR-2 signalling as an important therapeutic target in advanced gastric cancer. C1 [Fuchs, Charles S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Tomasek, Jiri] Masaryk Mem Canc Inst, Dept Complex Oncol Care, Brno, Czech Republic. [Yong, Cho Jae] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Med Oncol, Seoul, South Korea. [Dumitru, Filip] Emergency Cty Hosp Dr Constantin Opris, Dept Oncol, Baia Mare, Romania. [Passalacqua, Rodolfo] Ist Ospitalieri Cremona, Div Med Oncol, Cremona, Italy. [Goswami, Chanchal] BP Poddar Hosp & Med Res, Dept Med Oncol, Kolkata, W Bengal, India. [Safran, Howard] Brown Univ, Dept Med, Oncol Grp, Providence, RI 02912 USA. [dos Santos, Lucas Vieira] Hosp Canc Barretos & Hemomed, Inst Oncol Hematol, Gastrointestinal Oncol Div, Dept Oncol, Sao Paulo, Brazil. [Aprile, Giuseppe] Univ Udine, Dept Oncol, I-33100 Udine, Italy. [Aprile, Giuseppe] Gen Hosp, Udine, Italy. [Ferry, David R.] New Cross Hosp, Dept Med Oncol, Wolverhampton, W Midlands, England. [Melichar, Bohuslav] Palacky Univ, Sch Med, Dept Oncol, CR-77147 Olomouc, Czech Republic. [Melichar, Bohuslav] Teaching Hosp, Olomouc, Czech Republic. [Tehfe, Mustapha] CHUM, Hop Notre Dame, Dept Med Oncol, Montreal, PQ, Canada. [Topuzov, Eldar] Northwest State Med Univ II Mechnikov, Minist Healthcare Russian Federat, SBEIHPE, Moscow, Russia. [Zalcberg, John Raymond] Peter MacCallum Canc Ctr, Div Canc Med, East Melbourne, Vic, Australia. [Zalcberg, John Raymond] Univ Melbourne, Fac Med, Dept Med, Melbourne, Vic 3010, Australia. [Zalcberg, John Raymond] Univ Melbourne, Fac Med, Dept Oncol, Melbourne, Vic 3010, Australia. [Chau, Ian] Royal Marsden Hosp, Dept Med, London SW3 6JJ, England. [Chau, Ian] Royal Marsden Hosp, Dept Med, Surrey, England. [Campbell, William] Hosp Herrera Llerandi Clin Med, Dept Oncol, Guatemala City, Guatemala. [Sivanandan, Choondal] Reg Canc Ctr, Div Canc Res, Thiruvananthapuram, Kerala, India. [Pikiel, Joanna] Wojewodzkie Ctr Onkol Gdansk, Gdansk, Poland. [Koshiji, Minori; Hsu, Yanzhi; Gao, Ling; Schwartz, Jonathan D.] ImClone Syst LLC, Bridgewater, NJ USA. [Liepa, Astra M.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Tabernero, Josep] Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Dept Med Oncol, E-08193 Barcelona, Spain. RP Fuchs, CS (reprint author), Dana Farber Canc Inst, Gastrointestinal Oncol Div, Boston, MA 02215 USA. EM cfuchs@partners.org RI Santos, Lucas/K-3407-2013; Schwartsmann, Gilberto/G-4256-2016; Topuzov, Eldar/O-9523-2015; OI Santos, Lucas/0000-0002-2221-6692; Schwartsmann, Gilberto/0000-0002-7850-1644; Topuzov, Eldar/0000-0002-1700-1128; Amoroso, Vito/0000-0001-5357-5703 FU ImClone Systems FX ImClone Systems. NR 31 TC 445 Z9 469 U1 17 U2 85 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD JAN 4 PY 2014 VL 383 IS 9911 BP 31 EP 39 DI 10.1016/S0140-6736(13)61719-5 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 284SP UT WOS:000329341200033 PM 24094768 ER PT J AU McKenney, ML Schultz, KA Boyd, JH Byrd, JP Alloosh, M Teague, SD Arce-Esquivel, AA Fain, JN Laughlin, MH Sacks, HS Sturek, M AF McKenney, Mikaela L. Schultz, Kyle A. Boyd, Jack H. Byrd, James P. Alloosh, Mouhamad Teague, Shawn D. Arce-Esquivel, Arturo A. Fain, John N. Laughlin, M. Harold Sacks, Harold S. Sturek, Michael TI Epicardial adipose excision slows the progression of porcine coronary atherosclerosis SO JOURNAL OF CARDIOTHORACIC SURGERY LA English DT Article DE Atherosclerosis; Computed tomography; Surgery; Intravascular ultrasound ID METABOLIC SYNDROME; PERICARDIAL FAT; ARTERY-DISEASE; NONCONTRAST CT; T-CADHERIN; TISSUE; SWINE; EXPRESSION; RECEPTORS; EXERCISE AB Background: In humans there is a positive association between epicardial adipose tissue (EAT) volume and coronary atherosclerosis (CAD) burden. We tested the hypothesis that EAT contributes locally to CAD in a pig model. Methods: Ossabaw miniature swine (n = 9) were fed an atherogenic diet for 6 months to produce CAD. A 15 mm length by 3-5 mm width coronary EAT (cEAT) resection was performed over the middle segment of the left anterior descending artery (LAD) 15 mm distal to the left main bifurcation. Pigs recovered for 3 months on atherogenic diet. Intravascular ultrasound (IVUS) was performed in the LAD to quantify atheroma immediately after adipectomy and was repeated after recovery before sacrifice. Coronary wall biopsies were stained immunohistochemically for atherosclerosis markers and cytokines and cEAT was assayed for atherosclerosis-related genes by RT-PCR. Total EAT volume was measured by non-contrast CT before each IVUS. Results: Circumferential plaque length increased (p < 0.05) in the proximal and distal LAD segments from baseline until sacrifice whereas plaque length in the middle LAD segment underneath the adipectomy site did not increase. T-cadherin, scavenger receptor A and adiponectin were reduced in the intramural middle LAD. Relative to control pigs without CAD, 11 beta-hydroxysteroid dehydrogenase (11 beta HSD-1), CCL19, CCL21, prostaglandin D2 synthase, gp91phox [NADPH oxidase], VEGF, VEGFGR1, and angiotensinogen mRNAs were up-regulated in cEAT. EAT volume increased over 3 months. Conclusion: In pigs used as their own controls, resection of cEAT decreased the progression of CAD, suggesting that cEAT may exacerbate coronary atherosclerosis. C1 [McKenney, Mikaela L.; Schultz, Kyle A.; Byrd, James P.; Alloosh, Mouhamad; Sturek, Michael] Indiana Univ Sch Med, Dept Cellular, Indianapolis, IN 46202 USA. [McKenney, Mikaela L.; Schultz, Kyle A.; Byrd, James P.; Alloosh, Mouhamad; Sturek, Michael] Indiana Univ Sch Med, Dept Integrat Physiol, Indianapolis, IN 46202 USA. [Boyd, Jack H.] Indiana Univ Sch Med, Dept Cardiothorac Surg, Indianapolis, IN 46202 USA. [Teague, Shawn D.] Indiana Univ Sch Med, Dept Biol, Indianapolis, IN 46202 USA. [Arce-Esquivel, Arturo A.; Laughlin, M. Harold] Univ Missouri, Dept Biomed Sci, Columbia, MO 65211 USA. [Fain, John N.] Univ Tennessee, Dept Mol Sci, Hlth Sci Ctr, Memphis, TN 38163 USA. [Sacks, Harold S.] VA Greater Los Angeles Healthcare Syst, Endocrinol & Diabet Div, Los Angeles, CA 90073 USA. [Sacks, Harold S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Sturek, M (reprint author), Indiana Univ Sch Med, Dept Cellular, 635 Barnhill Dr,Room 385, Indianapolis, IN 46202 USA. EM msturek@iu.edu FU NIH [HL062552, P01 HL052490]; Cardiometabolic Disease Research Foundation, Los Angeles, CA; NIH/NCATS CTSI [TL1 TR000162] FX NIH HL062552 (MS, MLM, KAS, JPB, MA), P01 HL052490 (MHL), Cardiometabolic Disease Research Foundation, Los Angeles, CA (HS, MS), and NIH/NCATS CTSI TL1 TR000162 (MLM). NR 31 TC 24 Z9 25 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1749-8090 J9 J CARDIOTHORAC SURG JI J. Cardiothorac. Surg. PD JAN 3 PY 2014 VL 9 AR 2 DI 10.1186/1749-8090-9-2 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AB6GS UT WOS:000331886200002 PM 24387639 ER PT J AU Taylor, BK Fu, W Kuphal, KE Stiller, CO Winter, MK Chen, W Corder, GF Urban, JH McCarson, KE Marvizon, JC AF Taylor, B. K. Fu, W. Kuphal, K. E. Stiller, C. -O Winter, M. K. Chen, W. Corder, G. F. Urban, J. H. McCarson, K. E. Marvizon, J. C. TI INFLAMMATION ENHANCES Y1 RECEPTOR SIGNALING, NEUROPEPTIDE Y-MEDIATED INHIBITION OF HYPERALGESIA, AND SUBSTANCE P RELEASE FROM PRIMARY AFFERENT NEURONS SO NEUROSCIENCE LA English DT Article DE pain; G-protein; neurokinin-1 receptor; calcitonin gene-related peptide; isolectin B4; capsaicin ID RAT SPINAL-CORD; METHYL-D-ASPARTATE; DORSAL-HORN NEURONS; CENTRAL-NERVOUS-SYSTEM; IN-VIVO RELEASE; NEUROKININ-1 RECEPTOR; GABA(B) RECEPTORS; MESSENGER-RNA; SUBARACHNOID SPACE; TONIC INHIBITION AB Neuropeptide Y (NPY) is present in the superficial laminae of the dorsal horn and inhibits spinal nociceptive processing, but the mechanisms underlying its anti-hyperalgesic actions are unclear. We hypothesized that NPY acts at neuropeptide Y1 receptors in the dorsal horn to decrease nociception by inhibiting substance P (SP) release, and that these effects are enhanced by inflammation. To evaluate SP release, we used microdialysis and neurokinin 1 receptor (NK1R) internalization in rat. NPY decreased capsaicin-evoked SP-like immunoreactivity in the microdialysate of the dorsal horn. NPY also decreased non-noxious stimulus (paw brush)-evoked NK1R internalization (as well as mechanical hyperalgesia and mechanical and cold allodynia) after intraplantar injection of carrageenan. Similarly, in rat spinal cord slices with dorsal root attached, [Leu(31), Pro(34)]-NPY inhibited dorsal root stimulus-evoked NK1R internalization. In rat dorsal root ganglion neurons, Y1 receptors colocalized extensively with calcitonin gene-related peptide (CGRP). In dorsal horn neurons, Y1 receptors were extensively expressed and this may have masked the detection of terminal co-localization with CGRP or SP. To determine whether the pain inhibitory actions of Y1 receptors are enhanced by inflammation, we administered [Leu(31), Pro(34)]-NPY after intraplantar injection of complete Freund's adjuvant (CFA) in rat. We found that [Leu(31), Pro(34)]-NPY reduced paw clamp-induced NK1R internalization in CFA rats but not uninjured controls. To determine the contribution of increased Y1 receptor-G protein coupling, we measured [S-35]GTP gamma S binding simulated by [Leu(31), Pro(34)]-NPY in mouse dorsal horn. CFA inflammation increased the affinity of Y1 receptor G-protein coupling. We conclude that Y1 receptors contribute to the anti-hyperalgesic effects of NPY by mediating the inhibition of SP release, and that Y1 receptor signaling in the dorsal horn is enhanced during inflammatory nociception. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Taylor, B. K.; Fu, W.; Corder, G. F.] Univ Kentucky, Med Ctr, Sch Med, Dept Physiol, Lexington, KY 40536 USA. [Kuphal, K. E.] Univ Missouri, Div Pharmacol, Kansas City, MO 64110 USA. [Stiller, C. -O] Karolinska Inst, Karolinska Hosp, Dept Med, Div Clin Pharmacol, S-10401 Stockholm, Sweden. [Winter, M. K.; McCarson, K. E.] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66160 USA. [Chen, W.; Marvizon, J. C.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Chen, W.; Marvizon, J. C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Urban, J. H.] Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL USA. RP Taylor, BK (reprint author), Univ Kentucky, Med Ctr, Dept Physiol, 800 Rose St, Lexington, KY 40536 USA. EM brad.taylor@uky.edu OI Stiller, Carl-Olav/0000-0003-0684-635X FU NIH [R01NS45954, K02DA19656]; NICHD [HD02528] FX Supported by NIH R01NS45954 to B.K.T. and J.C.M. and K02DA19656 to B.K.T. and NICHD HD02528 to K.E.M. NR 78 TC 6 Z9 8 U1 2 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD JAN 3 PY 2014 VL 256 BP 178 EP 194 DI 10.1016/j.neuroscience.2013.10.054 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 300SY UT WOS:000330485500018 PM 24184981 ER PT J AU Han, XZ LaRosa, KB Kawai, T Taubman, MA AF Han, Xiaozhe LaRosa, Karen B. Kawai, Toshihisa Taubman, Martin A. TI DNA-based adaptive immunity protect host from infection-associated periodontal bone resorption via recognition of Porphyromonas gingivalis virulence component SO VACCINE LA English DT Article DE Immune response; Periodontal disease; Poiphyromonas gingivalis; Bacterial genomic DNA; Bone resorption; Vaccine ID BACTERIAL-DNA; DENDRITIC CELLS; GENOMIC DNA; ARG-GINGIPAIN; IMMUNIZATION; MICE; RESPONSES; FIMBRIAE; MUCOSAL; VACCINE AB Background: Porphyromonas gingivalis (Pg) is one of a constellation of oral organisms associated with human chronic periodontitis. While adaptive immunity to periodontal pathogen proteins has been investigated and is an important component of periodontal bone resorption, the effect of periodontal pathogen DNA in eliciting systemic and mucosal antibody and modulating immune responses has not been investigated. Methods: Rowett rats were locally injected with whole genomic Pg DNA in alum. Escherichia coli (Ec) genomic DNA, Fusobacterium nucleatum (Fn) genomic DNA, and saline/alum injected rats served as controls. After various time points, serum IgG and salivary IgA antibody to Ec, Fn or Pg were detected by ELISA. Serum and salivary antibody reactions with Pg surface antigens were determined by Western blot analyses and the specific antigen was identified by mass spectrometry. Effects of genomic DNA immunization on Pg bacterial colonization and experimental periodontal bone resorption were also evaluated. Results: Sera from Pg DNA, Ec DNA and Fn DNA-injected rats did not react with Ec or Fn bacteria. Serum IgG antibody levels to Pg and Pg surface extracts were significantly higher in animals immunized with Pg DNA as compared to the control groups. Rats injected with Pg DNA demonstrated a strong serum IgG and salivary IgA antibody reaction solely to Pg fimbrillin (41 kDa), the major protein component of Pg fimbriae. In the Pg DNA-immunized group, the numbers of Pg bacteria in oral cavity and the extent of periodontal bone resorption were significantly reduced after Pg infection. Conclusions: This study suggests that infected hosts may select specific genes from whole genomic DNA of the periodontal pathogen for transcription and presentation. The results indicate that the unique gene selected can initiate a host protective immune response to the parent bacterium. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Han, Xiaozhe; LaRosa, Karen B.; Kawai, Toshihisa; Taubman, Martin A.] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA 02142 USA. RP Han, XZ (reprint author), Forsyth Inst, Dept Immunol & Infect Dis, 245 1st St, Cambridge, MA 02142 USA. EM xhan@forsyth.org FU NIH from National Institute of Dental and Craniofacial Research (NIDCR) [DE-03420, DE-04733, DE-014551, DE-015254] FX The work described above was supported by NIH Grants DE-03420, DE-04733, DE-014551 and DE-015254 from National Institute of Dental and Craniofacial Research (NIDCR). NR 34 TC 3 Z9 3 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD JAN 3 PY 2014 VL 32 IS 2 BP 297 EP 303 DI 10.1016/j.vaccine.2013.09.004 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 290QH UT WOS:000329772900017 PM 24051159 ER PT J AU Orr, MT Beebe, EA Hudson, TE Moon, JJ Fox, CB Reed, SG Coler, RN AF Orr, Mark T. Beebe, Elyse A. Hudson, Thomas E. Moon, James J. Fox, Christopher B. Reed, Steven G. Coler, Rhea N. TI A Dual TLR Agonist Adjuvant Enhances the Immunogenicity and Protective Efficacy of the Tuberculosis Vaccine Antigen ID93 SO PLOS ONE LA English DT Article ID INDUCED INTERLEUKIN-12P70 SECRETION; T-CELL RESPONSES; DENDRITIC CELLS; INNATE IMMUNITY; EXPRESSION; LIGATION; PATHWAYS; LIGANDS; SYNERGY; MAGNITUDE AB With over eight million cases of tuberculosis each year there is a pressing need for the development of new vaccines against Mycobacterium tuberculosis. Subunit vaccines consisting of recombinant proteins are an attractive vaccine approach due to their inherent safety compared to attenuated live vaccines and the uniformity of manufacture. Addition of properly formulated TLR agonist-containing adjuvants to recombinant protein vaccines enhances the antigen-specific CD4(+) T cell response characterized by IFN-gamma and TNF, both of which are critical for the control of TB. We have developed a clinical stage vaccine candidate consisting of a recombinant fusion protein ID93 adjuvanted with the TLR4 agonist GLA-SE. Here we examine whether ID93+GLA-SE can be improved by the addition of a second TLR agonist. Addition of CpG containing DNA to ID93+GLA-SE enhanced the magnitude of the multi-functional T(H)1 response against ID93 characterized by co-production of IFN-gamma, TNF, and IL-2. Addition of CpG also improved the protective efficacy of ID93+GLA-SE. Finally we demonstrate that this adjuvant synergy between GLA and CpG is independent of TRIF signaling, whereas TRIF is necessary for the adjuvant activity of GLA-SE in the absence of CpG. C1 [Orr, Mark T.; Beebe, Elyse A.; Hudson, Thomas E.; Fox, Christopher B.; Reed, Steven G.; Coler, Rhea N.] Infect Dis Res Inst, Seattle, WA USA. [Moon, James J.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. [Moon, James J.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Charlestown, MA USA. [Moon, James J.] Harvard Univ, Sch Med, Charlestown, MA USA. [Coler, Rhea N.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA. RP Coler, RN (reprint author), Infect Dis Res Inst, Seattle, WA USA. EM rhea.coler@idri.org OI Fox, Christopher/0000-0002-4644-2619 FU National Institute Of Allergy And Infectious Diseases [U01AI078054, HHSN272200800045C] FX The project described was supported by Grant No. U01AI078054 and Contract No. HHSN272200800045C from the National Institute Of Allergy And Infectious Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript NR 44 TC 18 Z9 18 U1 2 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 3 PY 2014 VL 9 IS 1 AR e83884 DI 10.1371/journal.pone.0083884 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 286IH UT WOS:000329460800019 PM 24404140 ER PT J AU Roy, A Ganesh, G Sippola, H Bolin, S Sawesi, O Dagalv, A Schlenner, SM Feyerabend, T Rodewald, HR Kjellen, L Hellman, L Abrink, M AF Roy, Ananya Ganesh, Goutham Sippola, Helena Bolin, Sara Sawesi, Osama Dagalv, Anders Schlenner, Susan M. Feyerabend, Thorsten Rodewald, Hans-Reimer Kjellen, Lena Hellman, Lars Abrink, Magnus TI Mast Cell Chymase Degrades the Alarmins Heat Shock Protein 70, Biglycan, HMGB1, and Interleukin-33 (IL-33) and Limits Danger-induced Inflammation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Inflammation; Innate Immunity; Mast Cell; Serine Protease; Tumor Necrosis Factor (TNF); Virulence Factors; Biglycan; High Mobility Group Box Protein 1; Hsp70; IL-33 ID PRO-MATRIX METALLOPROTEASE-2; IL-1-LIKE CYTOKINE IL-33; HEAT-SHOCK PROTEINS; TOLL-LIKE; TRICHINELLA-SPIRALIS; CARBOXYPEPTIDASE-A; DELAYED EXPULSION; DENDRITIC CELLS; DYING CELLS; NO DAMPS AB During infection and tissue damage, virulence factors and alarmins are pro-inflammatory and induce activation of various immune cells including macrophages and mast cells (MCs). Activated MCs instantly release preformed inflammatory mediators, including several proteases. The chymase mouse mast cell protease (MCPT)-4 is thought to be pro-inflammatory, whereas human chymase also degrades pro-inflammatory cytokines, suggesting that chymase instead limits inflammation. Here we explored the contribution of MCPT4 and human chymase to the control of danger-induced inflammation. We found that protein extracts from wild type (WT), carboxypeptidase A3-, and MCPT6-deficient mice and MCs and recombinant human chymase efficiently degrade the Trichinella spiralis virulence factor heat shock protein 70 (Hsp70) as well as endogenous Hsp70. MC-(W-sash)-, serglycin-, NDST2-, and MCPT4-deficient extracts lacked this capacity, indicating that chymase is responsible for the degradation. Chymase, but not MC tryptase, also degraded other alarmins, i.e. biglycan, HMGB1, and IL-33, a degradation that was efficiently blocked by the chymase inhibitor chymostatin. IL-7, IL-22, GM-CSF, and CCL2 were resistant to chymase degradation. MCPT4-deficient conditions ex vivo and in vivo showed no reduction in added Hsp70 and only minor reduction of IL-33. Peritoneal challenge with Hsp70 resulted in increased neutrophil recruitment and TNF- levels in the MCPT4-deficient mice, whereas IL-6 and CCL2 levels were similar to the levels found in WT mice. The rapid and MC chymase-specific degradation of virulence factors and alarmins may depend on the presence of accessible extended recognition cleavage sites in target substrates and suggests a protective and regulatory role of MC chymase during danger-induced inflammation. C1 [Roy, Ananya; Ganesh, Goutham; Sippola, Helena; Bolin, Sara; Sawesi, Osama; Dagalv, Anders; Kjellen, Lena] Uppsala Univ, Dept Med Biochem & Microbiol, S-75123 Uppsala, Sweden. [Bolin, Sara] Uppsala Univ, Dept Immunol Genet & Pathol, S-75123 Uppsala, Sweden. [Hellman, Lars] Uppsala Univ, Dept Cell & Mol Biol, S-75123 Uppsala, Sweden. [Schlenner, Susan M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Feyerabend, Thorsten; Rodewald, Hans-Reimer] German Canc Res Ctr, Div Cellular Immunol, D-69120 Heidelberg, Germany. [Abrink, Magnus] Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Immunol Sect, S-75123 Uppsala, Sweden. RP Abrink, M (reprint author), Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Immunol Sect, BMC, Box 588, S-75123 Uppsala, Sweden. EM Magnus.Abrink@slu.se FU Swedish Research Council; FORMAS FX This research was supported by the Swedish Research Council and FORMAS (to M. A.) NR 65 TC 37 Z9 37 U1 2 U2 12 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 JAN 3 PY 2014 VL 289 IS 1 BP 237 EP 250 DI 10.1074/jbc.M112.435156 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 285CN UT WOS:000329370900021 PM 24257755 ER PT J AU Lim, SM Westover, KD Ficarro, SB Harrison, RA Choi, HG Pacold, ME Carrasco, M Hunter, J Kim, ND Xie, T Sim, T Janne, PA Meyerson, M Marto, JA Engen, JR Gray, NS AF Lim, Sang Min Westover, Kenneth D. Ficarro, Scott B. Harrison, Rane A. Choi, Hwan Geun Pacold, Michael E. Carrasco, Martin Hunter, John Kim, Nam Doo Xie, Ting Sim, Taebo Jaenne, Pasi A. Meyerson, Matthew Marto, Jarrod A. Engen, John R. Gray, Nathanael S. TI Therapeutic Targeting of Oncogenic K-Ras by a Covalent Catalytic Site Inhibitor SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE cancer; covalent inhibitors; drug design; K-Ras ID SIGNAL-TRANSDUCTION; KINASE INHIBITORS; CANCER; PROTEINS; PHOSPHATES; MUTATIONS; DOMAIN; SWITCH AB We report the synthesis of a GDP analogue, SML-8-73-1, and a prodrug derivative, SML-10-70-1, which are selective, direct-acting covalent inhibitors of the K-Ras G12C mutant relative to wild-type Ras. Biochemical and biophysical measurements suggest that modification of K-Ras with SML-8-73-1 renders the protein in an inactive state. These first-in-class covalent K-Ras inhibitors demonstrate that irreversible targeting of the K-Ras guanine-nucleotide binding site is potentially a viable therapeutic strategy for inhibition of Ras signaling. C1 [Lim, Sang Min; Ficarro, Scott B.; Choi, Hwan Geun; Pacold, Michael E.; Xie, Ting; Marto, Jarrod A.; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Lim, Sang Min; Choi, Hwan Geun; Xie, Ting; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Westover, Kenneth D.; Carrasco, Martin; Hunter, John] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. [Westover, Kenneth D.; Carrasco, Martin; Hunter, John] Univ Texas SW Med Ctr Dallas, Dept Radiat Oncol, Dallas, TX 75390 USA. [Harrison, Rane A.; Engen, John R.] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Lim, Sang Min; Xie, Ting] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Ficarro, Scott B.; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. [Pacold, Michael E.] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02139 USA. [Kim, Nam Doo] Daegu Gyeongbuk Med Innovat Fdn, New Drug Dev Ctr, Taegu 706010, South Korea. [Sim, Taebo] Korea Inst Sci & Technol, Chem Kinom Res Ctr, Seoul 130650, South Korea. [Jaenne, Pasi A.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Meyerson, Matthew] Broad Inst Harvard & MIT, Cambridge, MA 02141 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Gray, NS (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave, Boston, MA 02215 USA. EM Nathanael_Gray@dfci.harvard.edu FU CPRIT [R1207]; Welch Foundation [I1829]; NIH [P01NS047572]; Strategic Research Initiative at the Dana Farber Cancer Institute; Dana Farber Cancer Institute/Northeastern University Joint Program in Cancer Drug Development [NIH GM101135]; research collaboration with the Waters Corp; Sally Gordon Fellowship of the Damon Runyon Cancer Research Foundation [DRG 112-12]; DOD Breast Cancer Research Program Postdoctoral Fellowship [BC120208] FX This work was supported by CPRIT (R1207), The Welch Foundation (I1829), NIH P01NS047572, the Strategic Research Initiative at the Dana Farber Cancer Institute (J.A.M.), the Dana Farber Cancer Institute/Northeastern University Joint Program in Cancer Drug Development, NIH GM101135 (J.R.E.), a research collaboration with the Waters Corp (J.R.E.), Sally Gordon Fellowship of the Damon Runyon Cancer Research Foundation (DRG 112-12) (M.E.P.), DOD Breast Cancer Research Program Postdoctoral Fellowship (BC120208) (M. E. P.). NR 30 TC 82 Z9 82 U1 4 U2 56 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1433-7851 EI 1521-3773 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PD JAN 3 PY 2014 VL 53 IS 1 BP 199 EP 204 DI 10.1002/anie.201307387 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 275YI UT WOS:000328714900026 PM 24259466 ER PT J AU Dong, QH Sharma, S Liu, H Chen, L Gu, BX Sun, XN Wang, GY AF Dong, Qinghua Sharma, Sherven Liu, Hai Chen, Long Gu, Benxing Sun, Xiaonan Wang, Guanyu TI HDAC inhibitors reverse acquired radio resistance of KYSE-150R esophageal carcinoma cells by modulating Bmi-1 expression SO TOXICOLOGY LETTERS LA English DT Article DE Acquired radioresistance; HDIs; Bmi-1; Esophageal carcinoma; DNA repair ID HISTONE DEACETYLASE INHIBITOR; DNA-DAMAGE; TUMOR-CELLS; REPAIR; TRICHOSTATIN; ENHANCEMENT; RADIOSENSITIZATION; RADIORESISTANCE; THIOREDOXIN; P21(WAF1) AB Tumors treated with fractionated doses of ionizing radiation (IR) often acquire radioresistance. Although histone deacetylase inhibitors (HDIs) have been demonstrated to sensitize intrinsic radioresistant cancer cell lines to IR, little is known on the impact of HDIs on the effects of IR in acquired radioresistant cancer cells. This study evaluates the mechanisms by which HDIs sensitize acquired radioresistant esophageal squamous cell carcinoma cells to IR. The HDIs trichostatin A and sodium butyrate were tested for their ability to sensitize acquired radioresistant KYSE-150R and radiosensitive KYSE-150 parental cells to IR. Although the HDIs induced similar levels of cytotoxicity in the KYSE-150 and the KYSE-150R cells, HDIs increased the: (i) radiosensitivity, (ii) IR-induced ROS generation, and (iii) IR-induced G2/M arrest and apoptosis of KYSE-150R cells compared with those of KYSE-150 cells. These changes were accompanied by increased p21 expression and decreased mitochondrial membrane potential. When combined with IR, HDIs inhibited Bmi-1 expression in KYSE-150R cells and their ability to repair DNA damage. The results demonstrate the potential utility of HDIs in augmenting the efficacy of fractionated radiotherapy. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Dong, Qinghua; Chen, Long] Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Biomed Res Ctr, Hangzhou 310016, Zhejiang, Peoples R China. [Dong, Qinghua] China Natl Minist Educ, Key Lab Canc Prevent & Intervent, Hangzhou, Zhejiang, Peoples R China. [Sharma, Sherven] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Sharma, Sherven] US Dept Vet Affairs, Los Angeles, CA USA. [Liu, Hai; Gu, Benxing; Sun, Xiaonan] Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Radiotherapy, Hangzhou 310016, Zhejiang, Peoples R China. [Wang, Guanyu] Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Gen Surg, Hangzhou 310016, Zhejiang, Peoples R China. RP Wang, GY (reprint author), Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Gen Surg, Hangzhou 310016, Zhejiang, Peoples R China. EM wangguanyu@zju.edu.cn FU National Natural Science Foundation of China [81272493]; Science Technology Department of Zhejiang Province [2012R10047, 2012C33116]; Scientific Research Foundation for Returned Scholars by Ministry of Education of China; Zhejiang Educational Committee [Y201224108] FX This work was supported by the National Natural Science Foundation of China (No. 81272493), the Science Technology Department of Zhejiang Province (No. 2012R10047 and No. 2012C33116), Scientific Research Foundation for Returned Scholars by Ministry of Education of China and the Zhejiang Educational Committee (No. Y201224108). NR 36 TC 8 Z9 12 U1 2 U2 15 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 3 PY 2014 VL 224 IS 1 BP 121 EP 129 DI 10.1016/j.toxlet.2013.10.014 PG 9 WC Toxicology SC Toxicology GA 264OE UT WOS:000327887100016 PM 24459703 ER PT J AU Ballen, KK AF Ballen, Karen K. TI ATG for cord blood transplant: yes or no? SO BLOOD LA English DT Editorial Material ID HEMATOPOIETIC-CELL TRANSPLANTATION; IMMUNE RECONSTITUTION C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 10 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JAN 2 PY 2014 VL 123 IS 1 BP 7 EP 8 DI 10.1182/blood-2013-11-537001 PG 4 WC Hematology SC Hematology GA 290GJ UT WOS:000329742300005 PM 24385495 ER PT J AU Buitenkamp, TD Izraeli, S Zimmermann, M Forestier, E Heerema, NA van den Heuvel-Eibrink, MM Pieters, R Korbijn, CM Silverman, LB Schmiegelow, K Liang, DC Horibe, K Arico, M Biondi, A Basso, G Rabin, KR Schrappe, M Cario, G Mann, G Morak, M Panzer-Grumayer, R Mondelaers, V Lammens, T Cave, H Stark, B Ganmore, I Moorman, AV Vora, A Hunger, SP Pui, CH Mullighan, CG Manabe, A Escherich, G Kowalczyk, JR Whitlock, JA Zwaan, CM AF Buitenkamp, Trudy D. Izraeli, Shai Zimmermann, Martin Forestier, Erik Heerema, Nyla A. van den Heuvel-Eibrink, Marry M. Pieters, Rob Korbijn, Carin M. Silverman, Lewis B. Schmiegelow, Kjeld Liang, Der-Cheng Horibe, Keizo Arico, Maurizio Biondi, Andrea Basso, Giuseppe Rabin, Karin R. Schrappe, Martin Cario, Gunnar Mann, Georg Morak, Maria Panzer-Grumayer, Renate Mondelaers, Veerle Lammens, Tim Cave, Helene Stark, Batia Ganmore, Ithamar Moorman, Anthony V. Vora, Ajay Hunger, Stephen P. Pui, Ching-Hon Mullighan, Charles G. Manabe, Atsushi Escherich, Gabriele Kowalczyk, Jerzy R. Whitlock, James A. Zwaan, C. Michel TI Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study group SO BLOOD LA English DT Article ID BFM STUDY-GROUP; ONCOLOGY GROUP; B-PROGENITOR; CLINICAL CHARACTERISTICS; PEDIATRIC ONCOLOGY; CHILDHOOD; CRLF2; TRIALS; REARRANGEMENT; DISEASE AB Children with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials from 1995 to 2004. Non-DS BCP-ALL patients from the Dutch Child Oncology Group and Berlin-Frankfurt-Munster were reference cohorts. DS-ALL patients had a higher 8-year cumulative incidence of relapse (26% +/- 2% vs 15% +/- 1%, P < .001) and 2-year treatment-related mortality (TRM) (7% +/- 1% vs 2.0% +/- < 1%, P < .0001) than non-DS patients, resulting in lower 8-year event-free survival (EFS) (64% +/- 2% vs 81% +/- 2%, P < .0001) and overall survival (74% +/- 2% vs 89% +/- 1%, P < .0001). Independent favorable prognostic factors include age <6 years (hazard ratio [HR] = 0.58, P = .002), white blood cell (WBC) count <10 x 10(9)/L (HR = 0.60, P = .005), and ETV6-RUNX1 (HR = 0.14, P = .006) for EFS and age (HR = 0.48, P < .001), ETV6-RUNX1 (HR = 0.1, P = .016) and high hyperdiploidy (HeH) (HR = 0.29, P = .04) for relapse-free survival. TRM was the major cause of death in ETV6-RUNX1 and HeH DS-ALLs. Thus, while relapse is the main contributor to poorer survival in DS-ALL, infection-associated TRM was increased in all protocol elements, unrelated to treatment phase or regimen. Future strategies to improve outcome in DS-ALL should include improved supportive care throughout therapy and reduction of therapy in newly identified good-prognosis subgroups. C1 [Buitenkamp, Trudy D.; van den Heuvel-Eibrink, Marry M.; Pieters, Rob; Zwaan, C. Michel] Erasmus MC Sophia Childrens Hosp, Rotterdam, Netherlands. [Izraeli, Shai; Ganmore, Ithamar] Edmond & Lily Safra Childrens Hosp, Dept Paediat Haemato Oncol, Sheba Med Ctr, Ramat Gan, Israel. [Izraeli, Shai; Ganmore, Ithamar] Tel Aviv Univ, Sch Med, IL-69978 Tel Aviv, Israel. [Zimmermann, Martin] Hannover Med Sch, Stat Off, Berlin Frankfurt Munster Study Grp, Hannover, Germany. [Forestier, Erik] Umea Univ, Dept Med Biosci, Umea, Sweden. [Heerema, Nyla A.] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. [Pieters, Rob; Korbijn, Carin M.] Dutch Childhood Oncol Grp, The Hague, Netherlands. [Silverman, Lewis B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schmiegelow, Kjeld] Rigshosp, Univ Hosp, Juliane Marie Ctr, DK-2100 Copenhagen, Denmark. [Liang, Der-Cheng] Mackay Mem Hosp, Pediat Hematol Oncol Div, Taipei, Taiwan. [Horibe, Keizo] Nagoya Med Ctr, Natl Hosp Org, Clin Res Ctr, Nagoya, Aichi, Japan. [Arico, Maurizio] Azienda Osped Univ Meyer Children Hosp, Dept Pediat Hematol Oncol, Florence, Italy. [Biondi, Andrea] Univ Milano Bicocca, Osped S Gerardo, Dept Pediat, Monza, Italy. [Basso, Giuseppe] Univ Padua, Dept Pediat Salus Pueri, Padua, Italy. [Rabin, Karin R.] Baylor Coll Med, Texas Childrens Canc Ctr, Div Pediat Hematol Oncol, Houston, TX 77030 USA. [Schrappe, Martin; Cario, Gunnar] Univ Med Ctr Schleswig Holstein, Dept Pediat, Kiel, Germany. [Mann, Georg; Morak, Maria; Panzer-Grumayer, Renate] Univ Med Sch Vienna, St Anna Childrens Hosp, Childrens Canc Res Inst, Vienna, Austria. [Mondelaers, Veerle; Lammens, Tim] Ghent Univ Hosp, Dept Pediat Hematooncol, Ghent, Belgium. [Cave, Helene] Univ Paris Denis Diderot, Hop Robert Debre, AP HP, Dept Genet, Paris, France. [Stark, Batia] Schneider Childrens Med Ctr Israel, Ctr Pediat Hematol Oncol, Petah Tiqwa, Israel. [Stark, Batia] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Moorman, Anthony V.] Newcastle Univ, Leukaemia Res Cytogenet Grp, Northern Inst Canc Res, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Vora, Ajay] Sheffield Childrens Hosp, Dept Haematol, Sheffield, S Yorkshire, England. [Hunger, Stephen P.] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA. [Hunger, Stephen P.] Childrens Hosp, Aurora, CO USA. [Pui, Ching-Hon] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. [Mullighan, Charles G.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. [Manabe, Atsushi] St Lukes Int Hosp, Dept Pediat, Tokyo, Japan. [Escherich, Gabriele] Univ Med Ctr Hamburg Eppendorf, Clin Pediat Hematol & Oncol, Hamburg, Germany. [Kowalczyk, Jerzy R.] Med Univ Lublin, Dept Childrens Hematol & Oncol, Lublin, Poland. [Whitlock, James A.] Univ Toronto, Hosp Sick Children, Div Haematol Oncol, Toronto, ON M5G 1X8, Canada. RP Zwaan, CM (reprint author), Erasmus MC Sophia Childrens Hosp, Dept Pediat Oncol & Haematol, Dr Molewaterpl 60, NL-3015 GJ Rotterdam, Netherlands. EM shai.izraeli@sheba.health.gov.il; c.m.zwaan@erasmusmc.nl RI Moorman, Anthony/G-1468-2014; OI Moorman, Anthony/0000-0002-9781-6107; Mullighan, Charles/0000-0002-1871-1850; BASSO, GIUSEPPE/0000-0002-2634-9302 FU KiKa (Erasmus MC-Sophia Children's Hospital); Ergen Family Chair in Pediatric Cancer; Women's Auxiliary Millennium Chair in Haematology/Oncology; National Cancer Institute [CA 21765, 5 P01CA068484]; American Lebanese Syrian Associated Charities (SJCRH); Israel Cancer Association; Israel Science Foundation Legacy program; Israel Science Foundation iCORE program; Waxman Research Foundation; Israel Cancer Research Foundation; [CA98543]; [U10CA98413]; [U24 CA114766] FX This work was supported by KiKa (Erasmus MC-Sophia Children's Hospital) and in part by grants to the Children's Oncology Group, including CA98543, U10CA98413, and U24 CA114766; Ergen Family Chair in Pediatric Cancer (S.P.H.); Women's Auxiliary Millennium Chair in Haematology/Oncology (J.A.W.); National Cancer Institute grants CA 21765 (Saint Jude Children's Research Hospital [SJCRH]) and 5 P01CA068484 (Dana Farber Cancer Institute) (L.B.S.); the American Lebanese Syrian Associated Charities (SJCRH); and the Israel Cancer Association, Israel Science Foundation Legacy and iCORE programs, Waxman and Israel Cancer Research Foundations (S. I.). NR 55 TC 32 Z9 36 U1 1 U2 3 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 2 PY 2014 VL 123 IS 1 BP 70 EP 77 DI 10.1182/blood-2013-06-509463 PG 8 WC Hematology SC Hematology GA 290GJ UT WOS:000329742300016 PM 24222333 ER PT J AU Jiang, DF Aguiar, RCT AF Jiang, Daifeng Aguiar, Ricardo C. T. TI MicroRNA-155 controls RB phosphorylation in normal and malignant B lymphocytes via the noncanonical TGF-beta 1/SMAD5 signaling module SO BLOOD LA English DT Article ID GROWTH-FACTOR-BETA; CELL LYMPHOMA; TGF-BETA; PHOSPHODIESTERASE 4B; EXPRESSION; CANCER; SMAD; TRANSCRIPTION; RECEPTORS; COMPLEXES AB MicroRNA-155 (miR-155) plays pleiotropic roles in the biology of normal and malignant B lymphocytes, including the modulation of the transforming growth factor beta (TGF-beta) pathway via the targeting of SMAD5. However, the extent of the miR-155-mediated disruption of the TGF-beta 1/SMAD5 axis remains to be elucidated. To address this issue, we used the miR-155 knockout (KO) mouse and diffuse large B-cell lymphoma (DLBCL) cell lines ectopically expressing miR-155. In the DLBCL models, expression of miR-155 blocked TGF-beta 1-mediated activation of the retinoblastoma protein (RB), decreasing the abundance of the inhibitory pRB-E2F1 complex and limiting G0/G1 arrest. Genetic knockdown of SMAD5, p15, or p21 recapitulated these effects, establishing a circuitry whereby the targeting of SMAD5 by miR-155 blunts the TGF-beta 1-induced transcription of p15 and p21, thus sustaining RB phosphorylation and inactivity. Next, we demonstrated that SMAD5 levels are elevated in mature B lymphocytes from the miR-155 KO mice, which display a heightened sensitivity to TGF-beta 1 characterized by suppression of RB phosphorylation and more pronounced G0/G1 cell cycle arrest. Our findings suggest that a miR-155-mediated perturbation of the RB/E2F axis may play a role in DLBCL pathogenesis, and contribute to the reduced number of germinal center B cells and impaired T cell-dependent antibody response found in the miR-155 KO mice. C1 [Jiang, Daifeng; Aguiar, Ricardo C. T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hematol & Med Oncol, San Antonio, TX 78229 USA. [Aguiar, Ricardo C. T.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Aguiar, Ricardo C. T.] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA. [Aguiar, Ricardo C. T.] Audie Murphy VA Hosp, South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Aguiar, RCT (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM aguiarr@uthscsa.edu FU National Institutes of Health National Cancer Institute [R01-CA138747]; Young Investigator Award from the Voelcker Fund; National Institutes of Health National Cancer Institute Cancer Center [P30 CA054174] FX This work was supported by a grant from the National Institutes of Health National Cancer Institute (R01-CA138747) (R.C.T.A), a Young Investigator Award from the Voelcker Fund (R.C.T.A), and a National Institutes of Health National Cancer Institute Cancer Center Support Grant (P30 CA054174). NR 27 TC 15 Z9 15 U1 0 U2 7 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 2 PY 2014 VL 123 IS 1 BP 86 EP 93 DI 10.1182/blood-2013-07-515254 PG 8 WC Hematology SC Hematology GA 290GJ UT WOS:000329742300018 PM 24136167 ER PT J AU Savchenko, AS Borissoff, JI Martinod, K De Meyer, SF Gallant, M Erpenbeck, L Brill, A Wang, YM Wagner, DD AF Savchenko, Alexander S. Borissoff, Julian I. Martinod, Kimberly De Meyer, Simon F. Gallant, Maureen Erpenbeck, Luise Brill, Alexander Wang, Yanming Wagner, Denisa D. TI VWF-mediated leukocyte recruitment with chromatin decondensation by PAD4 increases myocardial ischemia/reperfusion injury in mice SO BLOOD LA English DT Article ID NEUTROPHIL EXTRACELLULAR TRAPS; DEEP-VEIN THROMBOSIS; REPERFUSION INJURY; DNA TRAPS; INFLAMMATORY RESPONSE; DEOXYRIBONUCLEASE-I; INFARCTION; ADAMTS13; ATHEROSCLEROSIS; HISTONES AB Innate immune cells play a major role in the early response to myocardial ischemia/reperfusion (MI/R) injury. Recombinant human ADAMTS13 (rhADAMTS13), cleaving von Willebrand factor (VWF), reduces leukocyte recruitment in mice. Death of cardiomyocytes and the possible formation of neutrophil extracellular traps (NETs) may result in chromatin release that is prothrombotic and cytotoxic. We investigated the pathophysiological role of extracellular chromatin during MI/R to evaluate the therapeutic potential of targeting extracellular DNA and VWF by using DNase I with/without rhADAMTS13. Finally, we examined the impact of histone citrullination and NETosis by peptidylarginine deiminase 4 (PAD4) on MI/R. We used a 24-hour MI/R mouse surgical model. MI/R injury caused an increase in plasma nucleosomes, abundant neutrophil infiltration, and the presence of citrullinated histone H3 at the site of injury. Both monotherapies and coadministration of DNase I and rhADAMTS13 revealed a cardioprotective effect, resulting in subsequent improvement of cardiac contractile function. PAD4(-/-) mice, which do not produce NETs, were also significantly protected from MI/R and DNase I treatment had no further beneficial effect. We demonstrate that extracellular chromatin released through NETosis exacerbates MI/R injury. Targeting both VWF-mediated leukocyte recruitment and chromatin removal may be a new therapeutic strategy to reduce ischemia-related cardiac damage. C1 [Savchenko, Alexander S.; Borissoff, Julian I.; Martinod, Kimberly; De Meyer, Simon F.; Gallant, Maureen; Erpenbeck, Luise; Brill, Alexander; Wagner, Denisa D.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Savchenko, Alexander S.; Borissoff, Julian I.; De Meyer, Simon F.; Erpenbeck, Luise; Brill, Alexander; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Martinod, Kimberly] Harvard Univ, Sch Med, Grad Program Immunol, Div Med Sci, Boston, MA USA. [Wang, Yanming] Penn State Univ, Ctr Eukaryot Gene Regulat, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. [Wagner, Denisa D.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, 3 Blackfan Circle,3rd Floor, Boston, MA 02115 USA. EM denisa.wagner@childrens.harvard.edu OI Martinod, Kimberly/0000-0002-1026-6107 FU National Heart, Lung, and Blood Institute of the National Institutes of Health [R01 HL041002, R01 HL102101]; Baxter Biosciences; National Cancer Institute [R01 CA136856]; Netherlands Organization for Scientific Research [825.11.019] FX This work was supported by National Heart, Lung, and Blood Institute of the National Institutes of Health grants R01 HL041002 and R01 HL102101 (D.D.W.), and a basic research grant from Baxter Biosciences. Research on the PAD4-/- mouse model was supported by National Cancer Institute grant R01 CA136856 (Y.W.).; J.I.B. is a recipient of a Rubicon fellowship (825.11.019) from the Netherlands Organization for Scientific Research. NR 50 TC 35 Z9 35 U1 0 U2 8 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 2 PY 2014 VL 123 IS 1 BP 141 EP 148 DI 10.1182/blood-2013-07-514992 PG 8 WC Hematology SC Hematology GA 290GJ UT WOS:000329742300025 PM 24200682 ER PT J AU Voth, WP Takahata, S Nishikawa, JL Metcalfe, BM Naar, AM Stillman, DJ AF Voth, Warren P. Takahata, Shinya Nishikawa, Joy L. Metcalfe, Benjamin M. Naeaer, Anders M. Stillman, David J. TI A Role for FACT in Repopulation of Nucleosomes at Inducible Genes SO PLOS ONE LA English DT Article ID RNA-POLYMERASE-II; TRANSCRIPTION ELONGATION-FACTORS; YEAST SACCHAROMYCES-CEREVISIAE; PLEIOTROPIC DRUG-RESISTANCE; MULTIDRUG-RESISTANCE; HISTONE CHAPERONE; ABC PROTEINS; IN-VIVO; CANDIDA-ALBICANS; H+-ATPASE AB Xenobiotic drugs induce Pleiotropic Drug Resistance (PDR) genes via the orthologous Pdr1/Pdr3 transcription activators. We previously identified the Mediator transcription co-activator complex as a key target of Pdr1 orthologs and demonstrated that Pdr1 interacts directly with the Gal11/Med15 subunit of the Mediator complex. Based on an interaction between Pdr1 and the FACT complex, we show that strains with spt16 or pob3 mutations are sensitive to xenobiotic drugs and display diminished PDR gene induction. Although FACT acts during the activation of some genes by assisting in the nucleosomes eviction at promoters, PDR promoters already contain nucleosome-depleted regions (NDRs) before induction. To determine the function of FACT at PDR genes, we examined the kinetics of RNA accumulation and changes in nucleosome occupancy following exposure to a xenobiotic drug in wild type and FACT mutant yeast strains. In the presence of normal FACT, PDR genes are transcribed within 5 minutes of xenobiotic stimulation and transcription returns to basal levels by 30-40 min. Nucleosomes are constitutively depleted in the promoter regions, are lost from the open reading frames during transcription, and the ORFs are wholly repopulated with nucleosomes as transcription ceases. While FACT mutations cause minor delays in activation of PDR genes, much more pronounced and significant defects in nucleosome repopulation in the ORFs are observed in FACT mutants upon transcription termination. FACT therefore has a major role in nucleosome redeposition following cessation of transcription at the PDR genes, the opposite of its better-known function in nucleosome disassembly. C1 [Voth, Warren P.; Takahata, Shinya; Metcalfe, Benjamin M.; Stillman, David J.] Univ Utah, Hlth Sci Ctr, Dept Pathol, Salt Lake City, UT 84132 USA. [Nishikawa, Joy L.; Naeaer, Anders M.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Nishikawa, Joy L.; Naeaer, Anders M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Stillman, DJ (reprint author), Univ Utah, Hlth Sci Ctr, Dept Pathol, Salt Lake City, UT 84132 USA. EM david.stillman@path.utah.edu OI Stillman, David/0000-0002-5268-2416 FU National Institutes of Health [GM39067, GM64649, GM071449] FX This work was supported by grants from the National Institutes of Health, grant GM39067 awarded to D.J.S, grant GM64649 awarded to Tim Formosa, and grant GM071449 awarded to A.M.N. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 70 TC 4 Z9 4 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 2 PY 2014 VL 9 IS 1 AR e84092 DI 10.1371/journal.pone.0084092 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 286ID UT WOS:000329460100031 PM 24392107 ER PT J AU Mullen, AC AF Mullen, Alan C. TI Hippo Tips the TGF-beta Scale in Favor of Pluripotency SO CELL STEM CELL LA English DT Editorial Material ID EMBRYONIC STEM-CELLS; ENDODERM; PATHWAY AB How TGF-beta signaling switches from enforcing pluripotency to promoting mesendodermal differentiation remains an open question. Recently in Cell Reports, Beyer et al. demonstrated that Hippo signaling components recruit the NuRD complex to repress expression of key genes targeted by TGF-beta and thus determine whether TGF-beta signaling will favor pluripotency or differentiation. C1 [Mullen, Alan C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Mullen, Alan C.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Mullen, AC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. EM acmullen@partners.org FU NIDDK NIH HHS [K08 DK090122] NR 10 TC 8 Z9 8 U1 0 U2 2 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 JAN 2 PY 2014 VL 14 IS 1 BP 6 EP 8 DI 10.1016/j.stem.2013.12.009 PG 4 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 287WB UT WOS:000329571900004 PM 24388171 ER PT J AU Xie, HF Xu, J Hsu, JH Nguyen, M Fujiwara, Y Peng, C Orkin, SH AF Xie, Huafeng Xu, Jian Hsu, Jessie H. Minh Nguyen Fujiwara, Yuko Peng, Cong Orkin, Stuart H. TI Polycomb Repressive Complex 2 Regulates Normal Hematopoietic Stem Cell Function in a Developmental-Stage-Specific Manner SO CELL STEM CELL LA English DT Article ID HISTONE METHYLTRANSFERASE EZH2; ACUTE LYMPHOBLASTIC-LEUKEMIA; GROUP PROTEIN EZH2; B-CELL; SOMATIC MUTATIONS; GENE EZH2; MYELOID MALIGNANCIES; PROGENITOR CELLS; PROSTATE-CANCER; SELF-RENEWAL AB Recent studies point to a pivotal role of Polycomb repressive complex 2 (PRC2) in stem cell function and cancer. Loss-of-function approaches targeting individual PRC2 subunits have, however, generated findings that are difficult to reconcile. Here, we prevent assembly of both Ezh1- and Ezh2-containing PRC2 complexes by conditional deletion of Eed, a core subunit, and assess hematopoiesis. We find that deletion of Eed exhausts adult bone marrow hematopoietic stem cells (HSCs), although fetal liver HSCs are produced in normal numbers. Eed-null neonatal HSCs express HSC signature genes but are defective in maintenance and differentiation. Comparative gene expression profiling revealed that neonatal and adult HSCs lacking Eed upregulated gene sets of conflicting pathways. Deletion of Cdkn2a, a PRC2 target gene, in Eed-null mice enhances hematopoietic stem/progenitor cell (HSPC) survival but fails to restore HSC functions. Taken together, our findings define developmental-stagespecific requirements for canonical PRC2 complexes in normal HSC function. C1 [Xie, Huafeng; Xu, Jian; Hsu, Jessie H.; Minh Nguyen; Fujiwara, Yuko; Peng, Cong; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Xie, Huafeng; Xu, Jian; Hsu, Jessie H.; Minh Nguyen; Fujiwara, Yuko; Peng, Cong; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Hematol Oncol,Harvard Stem Cell Inst, Boston, MA 02115 USA. [Fujiwara, Yuko; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu FU National Institutes of Health [CA105423]; Harvard Stem Cell Institute Blood Program; National Institute of Diabetes and Digestive and Kidney Diseases Career Development Award [K01DK093543] FX We gratefully acknowledge Matthias Stadtfeld, Jennifer Trowbridge, and Boris Wilson for critical review of the manuscript. This work was supported in part by National Institutes of Health U01 grant CA105423 and the Harvard Stem Cell Institute Blood Program. S.H.O. is an investigator of the Howard Hughes Medical Institute (HHMI). H. X. was a Leukemia and Lymphoma Society fellow. J.X., an HHMI-Helen Hay Whitney Foundation fellow, is supported by a National Institute of Diabetes and Digestive and Kidney Diseases Career Development Award K01DK093543. NR 60 TC 76 Z9 77 U1 1 U2 12 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 JAN 2 PY 2014 VL 14 IS 1 BP 68 EP 80 DI 10.1016/j.stem.2013.10.001 PG 13 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 287WB UT WOS:000329571900010 PM 24239285 ER PT J AU Baranoski, AS Meuser, E Hardy, H Closson, EF Mimiaga, MJ Safren, SA Virk, P Luk, R Skolnik, PR Kumar, VS AF Baranoski, Amy S. Meuser, Elizabeth Hardy, Helene Closson, Elizabeth F. Mimiaga, Matthew J. Safren, Steven A. Virk, Pushwaz Luk, Rowena Skolnik, Paul R. Kumar, Vikram S. TI Patient and provider perspectives on cellular phone-based technology to improve HIV treatment adherence SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE HIV; antiretroviral therapy; adherence; technology ID ANTIRETROVIRAL THERAPY AB Innovative techniques, potentially using technology, to improve adherence to antiretroviral therapy (ART) may help patients with HIV who struggle with self-care. This qualitative study compared patient and provider participants' perspectives on ART adherence and text messaging as a tool to promote adherence. Thirteen providers and 14 HIV-infected patients identified four main themes: (1) facilitators, (2) barriers to using text message reminders as a medium for ART medication reminders, (3) framing of text message reminders, and (4) patient responsibility and autonomy in the management of their health and wellness. Ease of use, access, convenience, and confidentiality were cited as benefits of a text message-based adherence intervention; while access, cost, difficulty manipulating cellular phones, lack of knowledge/education, and confidentiality were cited as potential barriers. Providers, but not patients, also identified patient apathy and time burden as potential barriers to a text message-based adherence reminder system. Patients and providers felt that personalization of messages, attention to timing, and confidentiality of messages were key factors for a successful text message-based adherence reminder system. Both providers and patients felt that patient responsibility and autonomy over an individual's own health care is an important issue in adherence to medical care. The majority of patients and providers felt that a text message-based adherence reminder system would be beneficial. While patients and providers had many similar views on factors influencing adherence with ART and the use of text messaging to improve adherence, there were some divergent views between the two groups. C1 [Baranoski, Amy S.; Hardy, Helene; Skolnik, Paul R.] Boston Univ, Sch Med, Dept Med, Infect Dis Sect, Boston, MA 02118 USA. [Baranoski, Amy S.; Meuser, Elizabeth; Hardy, Helene; Skolnik, Paul R.] Boston Med Ctr, Boston, MA USA. [Closson, Elizabeth F.; Mimiaga, Matthew J.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Mimiaga, Matthew J.; Safren, Steven A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mimiaga, Matthew J.; Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Virk, Pushwaz; Luk, Rowena; Kumar, Vikram S.] Dimagi Inc, Cambridge, MA USA. RP Baranoski, AS (reprint author), Drexel Univ, Coll Med, Div Infect Dis, Dept Med, Philadelphia, PA 19104 USA. EM amy.baranoski@drexelmed.edu FU NIMH NIH HHS [2 R44 MH080655-02, R44 MH080655] NR 15 TC 5 Z9 6 U1 1 U2 16 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD JAN 2 PY 2014 VL 26 IS 1 BP 26 EP 32 DI 10.1080/09540121.2013.802282 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 276DK UT WOS:000328728100004 PM 23742640 ER PT J AU Panos, SE Del Re, AC Thames, AD Arentsen, TJ Patel, SM Castellon, SA Singer, EJ Hinkin, CH AF Panos, Stella E. Del Re, A. C. Thames, April D. Arentsen, Timothy J. Patel, Sapna M. Castellon, Steven A. Singer, Elyse J. Hinkin, Charles H. TI The impact of neurobehavioral features on medication adherence in HIV: Evidence from longitudinal models SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE HIV; AIDS; antiretroviral therapy; adherence; neurobehavioral; psychosocial ID ANTIRETROVIRAL THERAPY; SELF-EFFICACY; PROTEASE INHIBITORS; INFECTED ADULTS; CLINICAL-TRIALS; DRUG-USERS; PREDICTORS; APATHY; INDIVIDUALS; DYSFUNCTION AB Effective antiretroviral therapy has led to substantial improvements in health-related outcomes among individuals with HIV. Despite advances in HIV pharmacotherapy, suboptimal medication adherence remains a significant barrier to successful treatment. Although several factors have been associated with medication adherence in the extant literature, study assessing the effects of some of the neurobehavioral features specific to HIV has been limited. Moreover, although there is a growing body of literature measuring medication adherence in HIV prospectively, few employ advanced statistical methodologies suited to handle advanced models with multiple predictors that would strengthen our understanding of medication adherence trajectories in HIV. This study sought to integrate traditionally assessed predictors of medication adherence with neurobehavioral features of HIV in a longitudinal study of medication adherence to combined antiretroviral therapy (cART). The current study used multilevel modeling to examine a wide arrangement of categories of factors - demographic, medication related, psychosocial, and neurobehavioral - on medication adherence. The sample consisted of 235 HIV+ individuals whose medication adherence was monitored over the course of six months using electronic monitoring devices. After controlling for the effects of demographic, medication, and psychosocial factors, neurobehavioral features added predictive validity to the model. In the final model, simultaneously controlling for the effects of each of the predictors within all the categories, age, self-efficacy, executive functioning, apathy, and frequency of stimulant use emerged as unique individual predictors of average medication adherence across the 6-month study. Self-efficacy and irritability predicted changes in medication adherence over time. Adherence behavior is multidetermined. Adequate assessment of these factors, combined with timely intervention, appears to be warranted in order to boost adherence rates. C1 [Panos, Stella E.; Thames, April D.; Arentsen, Timothy J.; Patel, Sapna M.; Castellon, Steven A.; Hinkin, Charles H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Panos, Stella E.; Thames, April D.; Arentsen, Timothy J.; Patel, Sapna M.; Castellon, Steven A.; Hinkin, Charles H.] VA Greater Los Angeles Healthcare Syst, Dept Psychol, Los Angeles, CA USA. [Del Re, A. C.] Stanford Univ, Sch Med, Dept Hlth Serv, Stanford, CA 94305 USA. [Del Re, A. C.] VA Palo Alto Healthcare Syst, Dept Psychol, Palo Alto, CA USA. [Singer, Elyse J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. RP Panos, SE (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. EM spanos@mednet.ucla.edu RI Thames, April/K-1964-2014; Del Re, A. C./N-2616-2014; OI Thames, April/0000-0001-8414-7189; Del Re, Aaron/0000-0002-9571-7623 FU NIDA NIH HHS [R01 DA13799, R01 DA013799]; NIMH NIH HHS [K23MH095661, T32 MH19535, T32 MH019535, K23 MH095661, U24 MH100929] NR 39 TC 8 Z9 8 U1 1 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD JAN 2 PY 2014 VL 26 IS 1 BP 79 EP 86 DI 10.1080/09540121.2013.802275 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 276DK UT WOS:000328728100010 PM 23756102 ER PT J AU Momplaisir, F Mounzer, K Long, JA AF Momplaisir, Florence Mounzer, Karam Long, Judith A. TI Preventive cancer screening practices in HIV-positive patients SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE cancer screening; HIV; primary care; model of care; preventive care ID UNITED-STATES; INFECTED WOMEN; OLDER; HEALTH; AIDS; AGE AB As patients with HIV age, they are at risk of developing non-AIDS defining malignancies. We performed a questionnaire study to evaluate colorectal and breast cancer screening among HIV-positive and HIV-negative patients seeking care from either an integrated (HIV/primary care), nonintegrated (specialized HIV), or general internal medicine clinic between August 2010 and July 2011. We performed a logistic regression to determine the odds of cancer screening. A total of 813 surveys were collected, and 762 were included in the analysis. As much as 401 were from HIV-positive patients. Patients with HIV were less likely to be current with their colorectal cancer screening (CRCS) (54.4% versus 65.0%, p=0.009); mammography rates were 24.3% versus 62.3% if done during the past year (p<0.001), and 42.0% versus 86.7% if done during the past 5 years (p<0.001). In adjusted models, the odds of colorectal cancer screening in HIV-positive patients compared to negative controls was not statistically significant (OR 0.8; 95% CI 0.5-1.3); however, HIV-positive women remained significantly less likely to be current with breast cancer screening (BCS) whether their mammogram was completed within 1 year (OR 0.1, 95% CI 0.1-0.2) or within 5 years (OR 0.1, 95% CI 0.0-0.2). Integrated care was not associated with improved screening; however, having frequent visits to a primary care physician (PCP) increased the likelihood of getting screened. BCS was lower in HIV-positive compared to HIV-negative women. Frequent visits to a PCPs improved cancer screening. C1 [Momplaisir, Florence] Temple Univ Hosp & Med Sch, Div Infect Dis, Philadelphia, PA 19140 USA. [Mounzer, Karam; Long, Judith A.] Univ Penn, Perelman Sch Med, Div Internal Med, Philadelphia, PA 19104 USA. [Mounzer, Karam] Jonathan Lax Ctr, Philadelphia FIGHT, Philadelphia, PA USA. [Long, Judith A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Momplaisir, F (reprint author), Temple Univ Hosp & Med Sch, Div Infect Dis, Philadelphia, PA 19140 USA. EM Florence.Momplaisir@tuhs.temple.edu NR 16 TC 4 Z9 4 U1 0 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD JAN 2 PY 2014 VL 26 IS 1 BP 87 EP 94 DI 10.1080/09540121.2013.802276 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 276DK UT WOS:000328728100011 PM 23742681 ER PT J AU Cooper, CJ Murphy, TP Cutlip, DE Jamerson, K Henrich, W Reid, DM Cohen, DJ Matsumoto, AH Steffes, M Jaff, MR Prince, MR Lewis, EF Tuttle, KR Shapiro, JI Rundback, JH Massaro, JM D'Agostino, RB Dworkin, LD AF Cooper, Christopher J. Murphy, Timothy P. Cutlip, Donald E. Jamerson, Kenneth Henrich, William Reid, Diane M. Cohen, David J. Matsumoto, Alan H. Steffes, Michael Jaff, Michael R. Prince, Martin R. Lewis, Eldrin F. Tuttle, Katherine R. Shapiro, Joseph I. Rundback, John H. Massaro, Joseph M. D'Agostino, Ralph B. Dworkin, Lance D. CA Coral Investigators TI Stenting and Medical Therapy for Atherosclerotic Renal-Artery Stenosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID UNSUCCESSFUL BALLOON ANGIOPLASTY; SYSTOLIC BLOOD-PRESSURE; RENOVASCULAR DISEASE; RANDOMIZED-TRIAL; HYPERTENSION; REVASCULARIZATION; PREVALENCE; PREVENTION; PLACEMENT AB BackgroundAtherosclerotic renal-artery stenosis is a common problem in the elderly. Despite two randomized trials that did not show a benefit of renal-artery stenting with respect to kidney function, the usefulness of stenting for the prevention of major adverse renal and cardiovascular events is uncertain. MethodsWe randomly assigned 947 participants who had atherosclerotic renal-artery stenosis and either systolic hypertension while taking two or more antihypertensive drugs or chronic kidney disease to medical therapy plus renal-artery stenting or medical therapy alone. Participants were followed for the occurrence of adverse cardiovascular and renal events (a composite end point of death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for congestive heart failure, progressive renal insufficiency, or the need for renal-replacement therapy). ResultsOver a median follow-up period of 43 months (interquartile range, 31 to 55), the rate of the primary composite end point did not differ significantly between participants who underwent stenting in addition to receiving medical therapy and those who received medical therapy alone (35.1% and 35.8%, respectively; hazard ratio with stenting, 0.94; 95% confidence interval [CI], 0.76 to 1.17; P=0.58). There were also no significant differences between the treatment groups in the rates of the individual components of the primary end point or in all-cause mortality. During follow-up, there was a consistent modest difference in systolic blood pressure favoring the stent group (-2.3 mm Hg; 95% CI, -4.4 to -0.2; P=0.03). ConclusionsRenal-artery stenting did not confer a significant benefit with respect to the prevention of clinical events when added to comprehensive, multifactorial medical therapy in people with atherosclerotic renal-artery stenosis and hypertension or chronic kidney disease. (Funded by the National Heart, Lung and Blood Institute and others; ClinicalTrials.gov number, NCT00081731.) C1 [Cooper, Christopher J.] Univ Toledo, Dept Med, Toledo, OH 43614 USA. [Murphy, Timothy P.; Dworkin, Lance D.] Rhode Isl Hosp, Providence, RI USA. [Murphy, Timothy P.; Dworkin, Lance D.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Cutlip, Donald E.; Massaro, Joseph M.; D'Agostino, Ralph B.] Harvard Clin Res Inst, Boston, MA USA. [Cutlip, Donald E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lewis, Eldrin F.] Brigham & Womens Hosp, Boston, MA 02115 USA. [D'Agostino, Ralph B.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Jamerson, Kenneth] Univ Michigan, Ann Arbor, MI 48109 USA. [Henrich, William] Univ Texas San Antonio, Hlth Sci Ctr, San Antonio, TX USA. [Reid, Diane M.] NHLBI, Bethesda, MD 20892 USA. [Cohen, David J.] Univ Missouri, Kansas City Sch Med, St Lukes Mid Amer Heart Inst, Kansas City, KS USA. [Matsumoto, Alan H.] Univ Virginia, Charlottesville, VA USA. [Steffes, Michael] Univ Minnesota, Minneapolis, MN USA. [Prince, Martin R.] Weill Cornell Med Ctr, New York, NY USA. [Tuttle, Katherine R.] Providence Sacred Heart Med Ctr, Spokane, WA USA. [Tuttle, Katherine R.] Univ Washington, Sch Med, Spokane, WA USA. [Shapiro, Joseph I.] Marshall Univ, Huntington, WV USA. [Rundback, John H.] Holy Name Med Ctr, Teaneck, NJ USA. RP Cooper, CJ (reprint author), Univ Toledo, Dept Med, 3000 Arlington Ave,MS 1036, Toledo, OH 43614 USA. EM christopher.cooper@utoledo.edu RI Prince, Martin/S-6850-2016; OI Mudge, David/0000-0002-4112-5550; Luft, Friedrich/0000-0002-8635-1199; Prince, Martin/0000-0002-9883-0584; Brilakis, Emmanouil/0000-0001-9416-9701 FU National Heart, Lung, and Blood Institute of the National Institutes of Health [U01HL071556, U01HL072734, U01HL072735, U01HL072736, U01HL072737]; Abbott; AstraZeneca; Eli Lilly; Medtronic; Boston Scientific; Biomet; Janssen; Medicines Company; Novartis; Amgen; Sanofi Aventis; VIVA Physicians; Covidien; Biotronik; St. Jude; CSI FX Supported by grants (U01HL071556, U01HL072734, U01HL072735, U01HL072736, and U01HL072737) from the National Heart, Lung, and Blood Institute of the National Institutes of Health.; Dr. Murphy reports holding equity interest in Summa Therapeutics. Dr. Cutlip reports that his institution holds research contracts with Medtronic, Boston Scientific, and Abbott Vascular. Dr. Cohen reports receiving personal fees from Abbott, AstraZeneca, Eli Lilly, and Medtronic, and grant support from Abbott, AstraZeneca, Eli Lilly, Medtronic, Boston Scientific, Biomet, and Janssen. Dr. Matsumoto reports receiving consulting fees from Boston Scientific and the Medicines Company and grant support from Medtronic, Cook and W. L. Gore. Dr. Jaff reports receiving consulting fees from AstraZeneca and serving as an uncompensated advisor to Cordis, Boston Scientific, Abbott, Covidien, and Medtronic. Dr. Lewis reports receiving grant support from Novartis, Amgen, and Sanofi Aventis. Dr. Tuttle reports receiving consulting fees and grant support from Eli Lilly. Dr. Rundback reports receiving fees for board membership from VIVA Physicians, personal fees from Covidien, Biotronik, and St. Jude, and lecture fees from Covidien and CSI. No other potential conflict of interest relevant to this article was reported. NR 26 TC 229 Z9 241 U1 1 U2 29 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 2 PY 2014 VL 370 IS 1 BP 13 EP 22 DI 10.1056/NEJMoa1310753 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 284XA UT WOS:000329354100006 PM 24245566 ER PT J AU Acker, MA Parides, MK Perrault, LP Moskowitz, AJ Gelijns, AC Voisine, P Smith, PK Hung, JW Blackstone, EH Puskas, JD Argenziano, M Gammie, JS Mack, M Ascheim, DD Bagiella, E Moquete, EG Ferguson, TB Horvath, KA Geller, NL Miller, MA Woo, YJ D'Alessandro, DA Ailawadi, G Dagenais, F Gardner, TJ O'Gara, PT Michler, RE Kron, IL AF Acker, Michael A. Parides, Michael K. Perrault, Louis P. Moskowitz, Alan J. Gelijns, Annetine C. Voisine, Pierre Smith, Peter K. Hung, Judy W. Blackstone, Eugene H. Puskas, John D. Argenziano, Michael Gammie, James S. Mack, Michael Ascheim, Deborah D. Bagiella, Emilia Moquete, Ellen G. Ferguson, T. Bruce Horvath, Keith A. Geller, Nancy L. Miller, Marissa A. Woo, Y. Joseph D'Alessandro, David A. Ailawadi, Gorav Dagenais, Francois Gardner, Timothy J. O'Gara, Patrick T. Michler, Robert E. Kron, Irving L. TI Mitral-Valve Repair versus Replacement for Severe Ischemic Mitral Regurgitation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LONG-TERM SURVIVAL; CARDIAC-RESYNCHRONIZATION THERAPY; END-SYSTOLIC VOLUME; HEART-FAILURE; MYOCARDIAL-INFARCTION; SURGICAL-MANAGEMENT; CLINICAL-TRIALS; DISEASE; IMPACT; CARDIOMYOPATHY AB BackgroundIschemic mitral regurgitation is associated with a substantial risk of death. Practice guidelines recommend surgery for patients with a severe form of this condition but acknowledge that the supporting evidence for repair or replacement is limited. MethodsWe randomly assigned 251 patients with severe ischemic mitral regurgitation to undergo either mitral-valve repair or chordal-sparing replacement in order to evaluate efficacy and safety. The primary end point was the left ventricular end-systolic volume index (LVESVI) at 12 months, as assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized below the lowest LVESVI rank. ResultsAt 12 months, the mean LVESVI among surviving patients was 54.625.0 ml per square meter of body-surface area in the repair group and 60.731.5 ml per square meter in the replacement group (mean change from baseline, -6.6 and -6.8 ml per square meter, respectively). The rate of death was 14.3% in the repair group and 17.6% in the replacement group (hazard ratio with repair, 0.79; 95% confidence interval, 0.42 to 1.47; P=0.45 by the log-rank test). There was no significant between-group difference in LVESVI after adjustment for death (z score, 1.33; P=0.18). The rate of moderate or severe recurrence of mitral regurgitation at 12 months was higher in the repair group than in the replacement group (32.6% vs. 2.3%, P<0.001). There were no significant between-group differences in the rate of a composite of major adverse cardiac or cerebrovascular events, in functional status, or in quality of life at 12 months. ConclusionsWe observed no significant difference in left ventricular reverse remodeling or survival at 12 months between patients who underwent mitral-valve repair and those who underwent mitral-valve replacement. Replacement provided a more durable correction of mitral regurgitation, but there was no significant between-group difference in clinical outcomes. (Funded by the National Institutes of Health and the Canadian Institutes of Health; ClinicalTrials.gov number, NCT00807040.) C1 [Acker, Michael A.; Woo, Y. Joseph] Univ Penn, Sch Med, Dept Surg, Div Cardiovasc Surg, Philadelphia, PA 19104 USA. [Parides, Michael K.; Moskowitz, Alan J.; Gelijns, Annetine C.; Ascheim, Deborah D.; Bagiella, Emilia; Moquete, Ellen G.] Mt Sinai Sch Med, Int Ctr Hlth Outcomes & Innovat Res, Dept Hlth Evidence & Policy, New York, NY USA. [Argenziano, Michael] Columbia Univ, Coll Phys & Surg, Div Cardiothorac Surg, Dept Surg, New York, NY 10027 USA. [D'Alessandro, David A.; Michler, Robert E.] Montefiore Med Ctr, Dept Cardiothorac Surg, New York, NY USA. [D'Alessandro, David A.; Michler, Robert E.] Albert Einstein Coll Med, New York, NY USA. [Perrault, Louis P.] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada. [Voisine, Pierre; Dagenais, Francois] Hop Laval, Inst Univ Cardiol Quebec, Quebec City, PQ, Canada. [Smith, Peter K.] Duke Univ, Med Ctr, Dept Surg, Div Cardiovasc & Thorac Surg, Durham, NC 27710 USA. [Ferguson, T. Bruce] E Carolina Univ, E Carolina Heart Inst, Dept Cardiovasc Sci, Greenville, NC USA. [Hung, Judy W.] Massachusetts Gen Hosp, Echocardiog Core Lab, Boston, MA 02114 USA. [O'Gara, Patrick T.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Blackstone, Eugene H.] Cleveland Clin Fdn, Dept Thorac & Cardiovasc Surg, Cleveland, OH USA. [Puskas, John D.] Emory Univ, Sch Med, Div Cardiothorac Surg, Clin Res Unit, Atlanta, GA 30322 USA. [Gammie, James S.] Univ Maryland, Sch Med, Div Cardiac Surg, Baltimore, MD 21201 USA. [Mack, Michael] Baylor Res Inst, Dallas, TX USA. [Horvath, Keith A.] Suburban Hosp, Ctr Heart, NIH, Bethesda, MD USA. [Geller, Nancy L.] Off Biostatist Res, Bethesda, MD USA. [Miller, Marissa A.] Div Cardiovasc Sci, Bethesda, MD USA. [Ailawadi, Gorav; Kron, Irving L.] Univ Virginia, Sch Med, Div Thorac & Cardiovasc Surg, Charlottesville, VA 22908 USA. [Gardner, Timothy J.] Ctr Heart & Vasc Hlth, Newark, DE USA. RP Gelijns, AC (reprint author), Icahn Sch Med Mt Sinai, Dept Hlth Evidence & Policy, 1 Gustave L Levy Pl,Box 1077, New York, NY 10029 USA. EM annetine.gelijns@mssm.edu OI Moskowitz, Alan/0000-0002-4412-9450 FU National Heart, Lung, and Blood Institute [U01 HL088942]; National Institute of Neurological Diseases and Stroke, National Institutes of Health; Canadian Institutes of Health Research FX Supported by a cooperative agreement (U01 HL088942) with the National Heart, Lung, and Blood Institute and the National Institute of Neurological Diseases and Stroke, National Institutes of Health, and by the Canadian Institutes of Health Research. NR 43 TC 195 Z9 199 U1 6 U2 23 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 2 PY 2014 VL 370 IS 1 BP 23 EP 32 DI 10.1056/NEJMoa1312808 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 284XA UT WOS:000329354100007 PM 24245543 ER PT J AU Anderson, TS Good, CB Gellad, WF AF Anderson, Timothy S. Good, Chester B. Gellad, Walid F. TI Macitentan and Pulmonary Arterial Hypertension SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter AB To the Editor: Pulido et al. (Aug. 29 issue)(1) report the results of the Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome (SERAPHIN), an Actelion Pharmaceuticals-funded study of macitentan to treat pulmonary arterial hypertension. Although the article provides potentially good news for patients, the authors note that Actelion Pharmaceuticals conducted all the statistical analyses and hired a professional medical writer to assist. The acknowledgments thank these persons, thus meeting the standards of the International Committee of Medical Journal Editors.(2) However, the blurred line between hired writing assistance and ghostwriting is unsettling. Disclosure is only ... C1 [Anderson, Timothy S.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. [Good, Chester B.; Gellad, Walid F.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Anderson, TS (reprint author), Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. EM andersont@upmc.edu NR 4 TC 0 Z9 0 U1 0 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 JAN 2 PY 2014 VL 370 IS 1 BP 81 EP 81 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 284XA UT WOS:000329354100018 PM 24382072 ER PT J AU Baxi, SM Greenblatt, RM Bacchetti, P Scherzer, R Minkoff, H Huang, Y Anastos, K Cohen, M Gange, SJ Young, M Shlipak, MG Gandhi, M AF Baxi, Sanjiv M. Greenblatt, Ruth M. Bacchetti, Peter Scherzer, Rebecca Minkoff, Howard Huang, Yong Anastos, Kathryn Cohen, Mardge Gange, Stephen J. Young, Mary Shlipak, Michael G. Gandhi, Monica TI Common clinical conditions - age, low BMI, ritonavir use, mild renal impairment - affect tenofovir pharmacokinetics in a large cohort of HIV-infected women SO AIDS LA English DT Article DE areas under the concentration-time curve; cystatin C; diverse populations; exposure; glomerular filtration rate; HIV-infected women; pharmacokinetics; tenofovir ID IMMUNODEFICIENCY-VIRUS-INFECTION; CO-FORMULATED ELVITEGRAVIR; CHRONIC KIDNEY-DISEASE; SERUM CYSTATIN-C; DISOPROXIL FUMARATE; PREEXPOSURE PROPHYLAXIS; ATAZANAVIR-RITONAVIR; INITIAL TREATMENT; INTERIM GUIDANCE; ESTIMATING GFR AB Objective:Tenofovir is used commonly in HIV treatment and prevention settings, but factors that correlate with tenofovir exposure in real-world settings are unknown.Design:Intensive pharmacokinetic studies of tenofovir in a large, diverse cohort of HIV-infected women over 24h at steady state were performed and factors that influenced exposure [assessed by areas under the concentration-time curves (AUCs)] identified.Methods:HIV-infected women (n=101) on tenofovir-based therapy underwent intensive 24-h pharmacokinetic sampling. Data on race/ethnicity, age, exogenous steroid use, menstrual cycle phase, concomitant medications, recreational drugs and/or tobacco, hepatic and renal function, weight, and BMI were collected. Multivariable models using forward stepwise selection identified factors associated with effects on AUC. Glomerular filtration rates (GFRs) prior to starting tenofovir were estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using both creatinine and cystatin-C measures.Results:The median (range) of tenofovir AUCs was 3350 (1031-13911) ngxh/ml. Higher AUCs were associated with concomitant ritonavir use (1.33-fold increase, P=0.002), increasing age (1.21-fold increase per decade, P=0.0007), and decreasing BMI (1.04-fold increase per 10% decrease in BMI). When GFR was calculated using cystatin-C measures, mild renal insufficiency prior to tenofovir initiation was associated with higher subsequent exposure (1.35-fold increase when pre-tenofovir GFR <70ml/min, P=0.0075).Conclusion:Concomitant ritonavir use, increasing age, decreasing BMI, and lower GFR prior to tenofovir initiation as estimated by cystatin C were all associated with elevated tenofovir exposure in a diverse cohort of HIV-infected women. Clinicians treating HIV-infected women should be aware of common clinical conditions that affect tenofovir exposure when prescribing this medication. C1 [Baxi, Sanjiv M.; Greenblatt, Ruth M.; Scherzer, Rebecca; Shlipak, Michael G.; Gandhi, Monica] Univ Calif San Francisco, Dept Med, San Francisco, CA 94122 USA. [Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94122 USA. [Greenblatt, Ruth M.; Bacchetti, Peter] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94122 USA. [Minkoff, Howard] Suny Downstate Med Ctr, Dept Med, Brooklyn, NY 11203 USA. [Huang, Yong] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94122 USA. [Anastos, Kathryn] Albert Einstein Univ, Dept Med, Bronx, NY USA. [Cohen, Mardge] Stroger Hosp, Dept Med, Chicago, IL USA. [Cohen, Mardge] Rush Univ, Chicago, IL 60612 USA. [Gange, Stephen J.] Johns Hopkins Univ, Dept Med, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Young, Mary] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. RP Gandhi, M (reprint author), Univ Calif San Francisco, Div HIV AIDS, 405 Irving St,2nd Floor, San Francisco, CA 94122 USA. EM monica.gandhi@ucsf.edu OI Gange, Stephen/0000-0001-7842-512X FU National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH) [K23 A1067065, RO1 AI098472]; National Center for Research Resources (NCRR)/NIH via the UCSF-CTSI [UL1 RR024131]; NIAID [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders FX This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH) (K23 A1067065 and RO1 AI098472 to M. G.). Additional funding is also provided by the National Center for Research Resources (NCRR)/NIH via the UCSF-CTSI (UL1 RR024131). Data in this study were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington DC, Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Chicago Consortium (Mardge Cohen); Data Coordinating Center (Stephen Gange). The WIHS is funded by NIAID (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. NR 49 TC 27 Z9 27 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JAN 2 PY 2014 VL 28 IS 1 BP 59 EP 66 DI 10.1097/QAD.0000000000000033 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 277KQ UT WOS:000328818400007 PM 24275255 ER PT J AU Weiser, SD Palar, K Frongillo, EA Tsai, AC Kumbakumba, E dePee, S Hunt, PW Ragland, K Martin, J Bangsberg, DR AF Weiser, Sheri D. Palar, Kartika Frongillo, Edward A. Tsai, Alexander C. Kumbakumba, Elias dePee, Saskia Hunt, Peter W. Ragland, Kathleen Martin, Jeffrey Bangsberg, David R. TI Longitudinal assessment of associations between food insecurity, antiretroviral adherence and HIV treatment outcomes in rural Uganda SO AIDS LA English DT Article DE AIDS; antiretroviral adherence; food insecurity; HIV; treatment outcomes; Uganda ID INFECTED INDIVIDUALS; SELF-REPORT; THERAPY; HIV/AIDS; SURVIVAL; AIDS; RECOMMENDATIONS; INTERVENTIONS; FRAMEWORK; SUPPORT AB Introduction:Food insecurity is a potentially important barrier to the success of antiretroviral therapy (ART) programs in resource-limited settings. We undertook a longitudinal study in rural Uganda to estimate the associations between food insecurity and HIV treatment outcomes.Design:Longitudinal cohort study.Methods:Participants were from the Uganda AIDS Rural Treatment Outcomes study and were followed quarterly for blood draws and structured interviews. We measured food insecurity with the validated Household Food Insecurity Access Scale. Our primary outcomes were: ART nonadherence (adherence <90%) measured by visual analog scale; incomplete viral load suppression (>400copies/ml); and low CD4(+) T-cell count (<350cells/l). We used generalized estimating equations to estimate the associations, adjusting for socio-demographic and clinical variables.Results:We followed 438 participants for a median of 33 months; 78.5% were food insecure at baseline. In adjusted analyses, food insecurity was associated with higher odds of ART nonadherence [adjusted odds ratio (AOR) 1.56, 95% confidence interval (CI) 1.10-2.20, P<0.05], incomplete viral suppression (AOR 1.52, 95% CI 1.18-1.96, P<0.01), and CD4(+) T-cell count less than 350 (AOR 1.47, 95% CI 1.24-1.74, P<0.01). Adding adherence as a covariate to the latter two models removed the association between food insecurity and viral suppression, but not between food insecurity and CD4(+) T-cell count.Conclusions:Food insecurity is longitudinally associated with poor HIV outcomes in rural Uganda. Intervention research is needed to determine the extent to which improved food security is causally related to improved HIV outcomes and to identify the most effective policies and programs to improve food security and health. C1 [Weiser, Sheri D.; Hunt, Peter W.; Ragland, Kathleen] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA 94143 USA. [Palar, Kartika] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Frongillo, Edward A.] Univ S Carolina, Dept Hlth Promot Educ & Behav, Arnold Sch Publ Hlth, Columbia, SC 29208 USA. [Tsai, Alexander C.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Kumbakumba, Elias; Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [dePee, Saskia] UN, World Food Programme, Rome, Italy. [Martin, Jeffrey] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Bangsberg, David R.] MIT, Ragon Inst MGH, Boston, MA USA. [Bangsberg, David R.] Harvard Univ, Boston, MA 02115 USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Dept Global Hlth & Social Equ, Boston, MA USA. [Bangsberg, David R.] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. RP Weiser, SD (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, POB 0874, San Francisco, CA 94143 USA. EM Sheri.Weiser@ucsf.edu RI Nguyen, Giang/D-9027-2016; OI Tsai, Alexander/0000-0001-6397-7917 FU National Institutes of Health [R01 MH054907, K23 MH079713, P30 AI027793, K23MH096620, K24MH087227]; Meyer Family Foundation; Burke Family Foundation; AHRQ [T32HS00046] FX Financial disclosure: The study was funded by the National Institutes of Health (R01 MH054907, K23 MH079713, and P30 AI027793) and the Meyer Family Foundation. The authors acknowledge the following additional sources of salary support: Burke Family Foundation (S. D. W.), AHRQ T32HS00046 (K. P.), NIH K23MH096620 (A. C. T.), and NIH K24MH087227 (D. R. B.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 28 Z9 29 U1 1 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JAN 2 PY 2014 VL 28 IS 1 BP 115 EP 120 DI 10.1097/01.aids.0000433238.93986.35 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 277KQ UT WOS:000328818400013 PM 23939234 ER PT J AU Mereish, EH O'Cleirigh, C Bradford, JB AF Mereish, Ethan H. O'Cleirigh, Conall Bradford, Judith B. TI Interrelationships between LGBT-based victimization, suicide, and substance use problems in a diverse sample of sexual and gender minorities SO PSYCHOLOGY HEALTH & MEDICINE LA English DT Article DE LGBT; victimization; suicide; substance use problems; sexual and gender minority stress ID MENTAL-HEALTH; GAY MEN; BISEXUAL ADULTS; SOCIAL STRESS; UNITED-STATES; ALCOHOL-USE; DISCRIMINATION; INDIVIDUALS; POPULATIONS; DISORDERS AB Research has documented significant relationships between sexual and gender minority stress and higher rates of suicidality (i.e. suicidal ideation and attempts) and substance use problems. We examined the potential mediating role of substance use problems on the relationship between sexual and gender minority stress (i.e. victimization based on lesbian, gay, bisexual, or transgender identity [LGBT]) and suicidality. A nonprobability sample of LGBT patients from a community health center (N=1457) ranged in age from 19-70years. Participants reported history of lifetime suicidal ideation and attempts, substance use problems, as well as experiences of LGBT-based verbal and physical attacks. Substance use problems were a significant partial mediator between LGBT-based victimization and suicidal ideation and between LGBT-based victimization and suicide attempts for sexual and gender minorities. Nuanced gender differences revealed that substance use problems did not significantly mediate the relationship between victimization and suicide attempts for sexual minority men. Substance use problems may be one insidious pathway that partially mediates the risk effects of sexual and gender minority stress on suicidality. Substances might be a temporary and deleterious coping resource in response to LGBT-based victimization, which have serious effects on suicidal ideation and behaviors. C1 [Mereish, Ethan H.] Boston Coll, Dept Counseling Dev & Educ Psychol, Chestnut Hill, MA 02167 USA. [O'Cleirigh, Conall] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Bradford, Judith B.] Fenway Hlth, Ctr Populat Res LGBT Hlth, Fenway Inst, Boston, MA USA. RP Mereish, EH (reprint author), Boston Coll, Dept Counseling Dev & Educ Psychol, Chestnut Hill, MA 02167 USA. EM mereish@bc.edu FU NICHD NIH HHS [R25 HD064426] NR 32 TC 17 Z9 17 U1 6 U2 61 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1354-8506 EI 1465-3966 J9 PSYCHOL HEALTH MED JI Psychol. Health Med. PD JAN 2 PY 2014 VL 19 IS 1 BP 1 EP 13 DI 10.1080/13548506.2013.780129 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 246TL UT WOS:000326561900001 PM 23535038 ER PT J AU Golberg, A AF Golberg, Alexander TI Analytical Model of Local Distribution of Chemicals in Tissues with First-Order-Rate Metabolism Kinetics SO CHEMICAL ENGINEERING COMMUNICATIONS LA English DT Article DE Electro chemotherapy; Percutaneous ethanol injection; Regional diffusion; Transport phenomena in tissues ID PERCUTANEOUS ETHANOL INJECTION; CONTINUOUS SPINAL-ANESTHESIA; TERM-FOLLOW-UP; HEPATOCELLULAR-CARCINOMA; ELECTRIC PULSES; ELECTROCHEMOTHERAPY; BLEOMYCIN; DIFFUSION; THERAPY; PHARMACOKINETICS AB The profile of regional distribution of chemicals in tissue is important for the development of novel locally applied therapies. Here we introduce an analytical approach for the temporal and spatial regional distribution of chemicals in living tissues. The new aspect of this model is in local chemical concentration dependence on the tissue perfusion rate, in addition to diffusion and metabolism rates. Using the Duhamel theorem we performed dimensionless and dimensional analysis for local chemical distribution and report on steady-state and transient solutions for tissues with the first-order kinetic rate of clearance by perfusion and metabolism. The predictions of our model are in good correlation with clinically observed data on percutaneous ethanol ablation of liver. Our results emphasize the importance of mathematical modeling that includes perfusion in the planning of therapies with local chemical distribution in living tissues. C1 [Golberg, Alexander] Univ Calif Berkeley, Dept Mech Engn, Berkeley, CA 94720 USA. RP Golberg, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med,Dept Surg, 51 Blossom St, Boston, MA 02114 USA. EM agolberg@gmail.com OI Golberg, Alexander/0000-0001-8782-8879 NR 49 TC 0 Z9 0 U1 0 U2 32 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0098-6445 J9 CHEM ENG COMMUN JI Chem. Eng. Commun. PD JAN 2 PY 2014 VL 201 IS 1 BP 102 EP 119 DI 10.1080/00986445.2012.762628 PG 18 WC Engineering, Chemical SC Engineering GA 225RG UT WOS:000324979400007 ER PT S AU Kelly, SK Ellersick, WF Krishnan, A Doyle, P Shire, DB Wyatt, JL Rizzo, JF AF Kelly, Shawn K. Ellersick, William F. Krishnan, Ashwati Doyle, Patrick Shire, Douglas B. Wyatt, John L. Rizzo, Joseph F. GP IEEE TI Redundant safety features in a high-channel-count retinal neurostimulator SO 2014 IEEE BIOMEDICAL CIRCUITS AND SYSTEMS CONFERENCE (BIOCAS) SE Biomedical Circuits and Systems Conference LA English DT Proceedings Paper CT IEEE Biomedical Circuits and Systems Conference (BioCAS) CY OCT 22-24, 2014 CL Lausanne, SWITZERLAND SP IEEE, IEEE Circuits & Syst Soc, Nano Tera, Medtronic Inc, gsk, Ecole Ploytechnique Federale Lausanne, CSEM, IEEE Engn Med & Biol Soc DE Biomedical engineering; biomedical electrodes; integrated circuit design; retinal prosthesis; retinal implant ID ELECTRICAL-STIMULATION; PROSTHESIS AB Safety features embedded in a 256-channel retinal prosthesis integrated circuit are presented. The biology of the retina and the electrochemistry of the electrode-tissue interface demand careful planning and design of the safety features of an implantable retinal stimulation device. We describe the internal limits and communication safety features of our ASIC, but we focus on monitoring and protection circuits for the electrode-issue interface. Two independent voltage monitoring circuits for each channel measure the electrode polarization voltage at two different times in the biphasic stimulation cycle. The monitors ensure that the charged electrode stays within the electrochemical water window potentials, and that the discharged electrode is within a small window near the counter electrode potential. A switch to connect each electrode to the counter electrode between pulses protects against a wide range of device failures. Additionally, we describe work on an active feedback system to ensure that the electrode voltage is at zero. C1 [Kelly, Shawn K.] Dept Vet Affairs, Pittsburgh, PA 15222 USA. [Kelly, Shawn K.; Wyatt, John L.] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Doyle, Patrick] Analog Circuit Works, Sudbury, MA USA. [Ellersick, William F.] Harvest Automat, Billerica, MA USA. [Krishnan, Ashwati] Cornell Univ, Ithaca, NY USA. [Shire, Douglas B.] MIT, Cambridge, MA 02139 USA. [Rizzo, Joseph F.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Kelly, SK (reprint author), Dept Vet Affairs, Pittsburgh, PA 15222 USA. EM skkelly@cmu.edu NR 13 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2163-4025 BN 978-1-4799-2346-5 J9 BIOMED CIRC SYST C PY 2014 BP 216 EP 219 PG 4 WC Computer Science, Information Systems; Engineering, Biomedical; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BE0HN UT WOS:000366049300072 ER PT J AU Thase, ME Swartz, HA Frank, E Miklowitz, DJ Gabbard, GO Goldberg, JF AF Thase, Michael E. Swartz, Holly A. Frank, Ellen Miklowitz, David J. Gabbard, Glen O. Goldberg, Joseph F. BA Gabbard, GO BF Gabbard, GO TI Psychotherapy of Mood Disorders SO GABBARD'S TREATMENTS OF PSYCHIATRIC DISORDERS, 5TH EDITION LA English DT Article; Book Chapter ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; FAMILY-FOCUSED TREATMENT; SOCIAL RHYTHM THERAPY; COLLABORATIVE RESEARCH-PROGRAM; PEDIATRIC-BIPOLAR-DISORDER; MAJOR DEPRESSIVE DISORDER; MENTAL-HEALTH TREATMENT; EXPRESSED EMOTION; PSYCHOSOCIAL TREATMENT C1 [Thase, Michael E.] Univ Penn, Perelman Sch Med, Psychiat, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Swartz, Holly A.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Frank, Ellen] Univ Penn, Psychiat, Philadelphia, PA 19104 USA. [Frank, Ellen] Univ Penn, Dept Psychol, Clin Program, Psychol, Philadelphia, PA 19104 USA. [Miklowitz, David J.] UCLA Semel Inst Neurosci & Human Behav, Psychiat, Los Angeles, CA USA. [Miklowitz, David J.] UCLA Semel Inst Neurosci & Human Behav, Child & Adolescent Mood Disorders Program, Los Angeles, CA USA. [Gabbard, Glen O.] SUNY Upstate Med Univ, Psychiat, Syracuse, NY 13210 USA. [Gabbard, Glen O.] Baylor Coll Med, Psychiat, Houston, TX 77030 USA. [Gabbard, Glen O.] Gabbard Ctr, Houston, TX USA. [Goldberg, Joseph F.] Icahn Sch Med Mt Sinai, Psychiat, New York, NY 10029 USA. [Goldberg, Joseph F.] Silver Hill Hosp, Affect Disorders Res Program, New Canaan, CT USA. RP Thase, ME (reprint author), Univ Penn, Perelman Sch Med, Psychiat, Philadelphia, PA 19104 USA. NR 83 TC 0 Z9 0 U1 1 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209 USA BN 978-1-58562-442-3 PY 2014 BP 221 EP 248 PG 28 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BD9FX UT WOS:000364632600016 ER PT J AU George, MS Taylor, JJ Short, EB Snipes, J Pelic, C Fryml, LD AF George, Mark S. Taylor, Joseph J. Short, E. Baron Snipes, Jonathan Pelic, Christopher Fryml, Leah D. BA Gabbard, GO BF Gabbard, GO TI Brain Stimulation Treatments for Mood Disorders SO GABBARD'S TREATMENTS OF PSYCHIATRIC DISORDERS, 5TH EDITION LA English DT Article; Book Chapter ID TRANSCRANIAL MAGNETIC STIMULATION; VAGUS NERVE-STIMULATION; TREATMENT-RESISTANT DEPRESSION; OBSESSIVE-COMPULSIVE DISORDER; LEFT PREFRONTAL RTMS; HUMAN MOTOR CORTEX; ADMINISTERED SEIZURE THERAPY; INTENSITY FOCUSED ULTRASOUND; RANDOMIZED CONTROLLED-TRIAL; SHAM-CONTROLLED TRIAL C1 [George, Mark S.] Med Univ S Carolina, Layton McCurdy Endowed Chair, Psychiat Radiol & Neurosci, Charleston, SC 29403 USA. [George, Mark S.] Med Univ S Carolina, BSL, Charleston, SC USA. [George, Mark S.] RH Johnson VA Med Ctr, Charleston, SC USA. [Taylor, Joseph J.; Short, E. Baron; Snipes, Jonathan; Fryml, Leah D.] Med Univ S Carolina, Charleston, SC 29425 USA. [Pelic, Christopher] Med Univ S Carolina, Coll Med, Student Career Planning, Charleston, SC 29425 USA. [Pelic, Christopher] Med Univ S Carolina, South Carolina Alpha Chapter, Charleston, SC 29425 USA. [Pelic, Christopher] Med Univ S Carolina, Neurol Psychiat Combined Program, Charleston, SC 29425 USA. [Pelic, Christopher] Med Univ S Carolina, Ralph H Johnson VA Hosp, Charleston, SC 29425 USA. RP George, MS (reprint author), Med Univ S Carolina, Layton McCurdy Endowed Chair, Psychiat Radiol & Neurosci, Charleston, SC 29403 USA. NR 160 TC 1 Z9 1 U1 2 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209 USA BN 978-1-58562-442-3 PY 2014 BP 303 EP 337 PG 35 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BD9FX UT WOS:000364632600019 ER PT J AU Stein, MB Yang, CT Campbell-Sills, L AF Stein, Murray B. Yang, Calvin T. Campbell-Sills, Laura BA Gabbard, GO BF Gabbard, GO TI Panic Disorder SO GABBARD'S TREATMENTS OF PSYCHIATRIC DISORDERS, 5TH EDITION LA English DT Article; Book Chapter ID COGNITIVE-BEHAVIORAL THERAPY; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; ANXIETY DISORDERS; EXTENDED-RELEASE; ALPRAZOLAM DISCONTINUATION; PROGNOSTIC INDEXES; RANDOMIZED-TRIAL; STANDARD CBT; FOLLOW-UP C1 [Stein, Murray B.] Univ Calif San Diego, Psychiat & Family & Prevent Med, San Diego, CA 92103 USA. [Stein, Murray B.] VA San Diego Healthcare Syst, San Diego, CA USA. [Yang, Calvin T.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Yang, Calvin T.] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Campbell-Sills, Laura] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Stein, MB (reprint author), Univ Calif San Diego, Psychiat & Family & Prevent Med, San Diego, CA 92103 USA. NR 44 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209 USA BN 978-1-58562-442-3 PY 2014 BP 343 EP 355 PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BD9FX UT WOS:000364632600021 ER PT J AU Gerstenblith, TA Stern, TA AF Gerstenblith, Ted Avi Stern, Theodore A. BA Gabbard, GO BF Gabbard, GO TI Primary Care and Consultation-Liaison Interventions for Somatic Symptom and Related Disorders SO GABBARD'S TREATMENTS OF PSYCHIATRIC DISORDERS, 5TH EDITION LA English DT Article; Book Chapter ID UNEXPLAINED PHYSICAL SYMPTOMS; MANAGEMENT; DIAGNOSIS; HYSTERIA; MUPS C1 [Gerstenblith, Ted Avi] Massachusetts Gen Hosp, Psychosomat Med, Boston, MA 02114 USA. [Gerstenblith, Ted Avi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat, Boston, MA USA. [Stern, Theodore A.] Massachusetts Gen Hosp, Avery D Weisman Psychiat Consultat Serv, Boston, MA 02114 USA. [Stern, Theodore A.] Massachusetts Gen Hosp, Off Clin Careers, Boston, MA 02114 USA. [Stern, Theodore A.] Harvard Univ, Sch Med, Psychiat Field Psychosomat Med Consultat, Boston, MA USA. RP Gerstenblith, TA (reprint author), Massachusetts Gen Hosp, Psychosomat Med, Boston, MA 02114 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209 USA BN 978-1-58562-442-3 PY 2014 BP 571 EP 582 PG 12 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BD9FX UT WOS:000364632600040 ER PT J AU Belstrom, D Holmstrup, P Nielsen, CH Kirkby, N Twetman, S Heitmann, BL Klepac-Ceraj, V Paster, BJ Fiehn, NE AF Belstrom, Daniel Holmstrup, Palle Nielsen, Claus H. Kirkby, Nikolai Twetman, Svante Heitmann, Berit L. Klepac-Ceraj, Vanja Paster, Bruce J. Fiehn, Nils-Erik TI Bacterial profiles of saliva in relation to diet, lifestyle factors, and socioeconomic status SO JOURNAL OF ORAL MICROBIOLOGY LA English DT Article DE saliva; HOMIM; bacteria; diet lifestyle ID ORAL-HEALTH; DENTAL-CARIES; PERIODONTITIS; MICROBIOME; DIVERSITY; DISEASE; INFLAMMATION; MICROARRAY; ALCOHOL; LESIONS AB Background and objective: The bacterial profile of saliva is composed of bacteria from different oral surfaces. The objective of this study was to determine whether different diet intake, lifestyle, or socioeconomic status is associated with characteristic bacterial saliva profiles. Design: Stimulated saliva samples from 292 participants with low levels of dental caries and periodontitis, enrolled in the Danish Health Examination Survey (DANHES), were analyzed for the presence of approximately 300 bacterial species by means of the Human Oral Microbe Identification Microarray (HOMIM). Using presence and levels (mean HOMIM-value) of bacterial probes as endpoints, the influence of diet intake, lifestyle, and socioeconomic status on the bacterial saliva profile was analyzed by Mann-Whitney tests with Benjamini-Hochberg's correction for multiple comparisons and principal component analysis. Results: Targets for 131 different probes were identified in 292 samples, with Streptococcus and Veillonella being the most predominant genera identified. Two bacterial taxa (Streptococcus sobrinus and Eubacterium [11][G-3] brachy) were more associated with smokers than non-smokers (adjusted p-value <0.01). Stratification of the group based on extreme ends of the parameters age, gender, alcohol consumption, body mass index (BMI), and diet intake had no statistical influence on the composition of the bacterial profile of saliva. Conversely, differences in socioeconomic status were reflected by the bacterial profiles of saliva. Conclusions: The bacterial profile of saliva seems independent of diet intake, but influenced by smoking and maybe socioeconomic status. C1 [Belstrom, Daniel; Holmstrup, Palle] Univ Copenhagen, Fac Hlth Sci, Sch Dent, Sect Periodontol, Copenhagen, Denmark. [Nielsen, Claus H.] Rigshosp, Copenhagen Univ Hosp, Dept Infect Dis & Rheumatol, Inst Inflammat Res, DK-2100 Copenhagen, Denmark. [Kirkby, Nikolai] Rigshosp, Copenhagen Univ Hosp, Dept Med Microbiol, DK-2100 Copenhagen, Denmark. [Twetman, Svante] Univ Copenhagen, Fac Hlth Sci, Sch Dent, Sect Cariol, DK-1168 Copenhagen, Denmark. [Heitmann, Berit L.] Bispebejerg Hosp, Inst Prevent Med, Copenhagen, Denmark. [Heitmann, Berit L.] Frederiksberg Univ Hosp, Inst Prevent Med, Copenhagen, Denmark. [Heitmann, Berit L.] Univ Sydney, Boden Inst Obes Nutr Exercise & Eating Disorders, Sydney, NSW 2006, Australia. [Heitmann, Berit L.] Univ Southern Denmark, Natl Inst Publ Hlth, Copenhagen, Denmark. [Klepac-Ceraj, Vanja] Wellesley Coll, Dept Biol Sci, Wellesley, MA 02181 USA. [Paster, Bruce J.] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. [Paster, Bruce J.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Fiehn, Nils-Erik] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark. RP Belstrom, D (reprint author), Univ Copenhagen, Fac Hlth Sci, Sch Dent, Sect Periodontol, Copenhagen, Denmark. EM dbel@sund.ku.dk OI Klepac-Ceraj, Vanja/0000-0001-5387-5706 FU Danish Dental Association; Danish Foundation for Mutual Efforts in Dental Care; TrygFonden; Health Insurance Foundation; Simon Spies Foundation FX The authors declare no conflicts of interest in this study. This study was supported by external financial support from the following: the Danish Dental Association, the Danish Foundation for Mutual Efforts in Dental Care, TrygFonden, the Health Insurance Foundation, and the Simon Spies Foundation. NR 38 TC 13 Z9 13 U1 4 U2 11 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-2297 J9 J ORAL MICROBIOL JI J. Oral Microbiology PY 2014 VL 6 AR 23609 DI 10.3402/jom.v6.23609 PG 9 WC Microbiology SC Microbiology GA CX4LS UT WOS:000365673000001 ER PT J AU Camanocha, A Dewhirst, FE AF Camanocha, Anuj Dewhirst, Floyd E. TI Host-associated bacterial taxa from Chlorobi, Chloroflexi, GN02, Synergistetes, SR1, TM7, and WPS-2 Phyla/candidate divisions SO JOURNAL OF ORAL MICROBIOLOGY LA English DT Article DE microbiome; primers; cloning; phylogeny; 16S rRNA ID 16S RIBOSOMAL-RNA; HUMAN SUBGINGIVAL PLAQUE; GEN. NOV.; PHYLUM CHLOROFLEXI; EMENDED DESCRIPTION; ORAL-CAVITY; SKIN MICROBIOME; DOMAIN BACTERIA; DARK-MATTER; CLASSIS NOV AB Background and objective: In addition to the well-known phyla Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, Spirochaetes, Fusobacteria, Tenericutes, and Chylamydiae, the oral microbiomes of mammals contain species from the lesser-known phyla or candidate divisions, including Synergistetes, TM7, Chlorobi, Chloroflexi, GN02, SR1, and WPS-2. The objectives of this study were to create phyla-selective 16S rDNA PCR primer pairs, create selective 16S rDNA clone libraries, identify novel oral taxa, and update canine and human oral microbiome databases. Design: 16S rRNA gene sequences for members of the lesser-known phyla were downloaded from GenBank and Greengenes databases and aligned with sequences in our RNA databases. Primers with potential phylum level selectivity were designed heuristically with the goal of producing nearly full-length 16S rDNA amplicons. The specificity of primer pairs was examined by making clone libraries from PCR amplicons and determining phyla identity by BLASTN analysis. Results: Phylum-selective primer pairs were identified that allowed construction of clone libraries with 96-100% specificity for each of the lesser-known phyla. From these clone libraries, seven human and two canine novel oral taxa were identified and added to their respective taxonomic databases. For each phylum, genome sequences closest to human oral taxa were identified and added to the Human Oral Microbiome Database to facilitate metagenomic, transcriptomic, and proteomic studies that involve tiling sequences to the most closely related taxon. While examining ribosomal operons in lesser-known phyla from single-cell genomes and metagenomes, we identified a novel rRNA operon order (23S-5S-16S) in three SR1 genomes and the splitting of the 23S rRNA gene by an I-CeuI-like homing endonuclease in a WPS-2 genome. Conclusions: This study developed useful primer pairs for making phylum-selective 16S rRNA clone libraries. Phylum-specific libraries were shown to be useful for identifying previously unrecognized taxa in lesser-known phyla and would be useful for future environmental and host-associated studies. C1 [Camanocha, Anuj; Dewhirst, Floyd E.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Dewhirst, Floyd E.] Forsyth Inst, Dept Microbiol, Cambridge, MA 02115 USA. RP Dewhirst, FE (reprint author), Forsyth Inst, Dept Microbiol, 245 First St, Cambridge, MA 02115 USA. EM fdewhirst@forsyth.org FU National Institute of Dental and Craniofacial Research of the National Institutes of Health [R37DE016937] FX The authors thank David A. Relman, Julie A. Segre, Norman R. Pace, and other investigators who have contributed vast numbers of nearly full-length high quality 16S rRNA sequences to GenBank for mining by the research community. Research reported in this publication was supported by The National Institute of Dental and Craniofacial Research of the National Institutes of Health under award number R37DE016937. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 62 TC 6 Z9 7 U1 7 U2 8 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-2297 J9 J ORAL MICROBIOL JI J. Oral Microbiology PY 2014 VL 6 AR 25468 DI 10.3402/jom.v6.25468 PG 22 WC Microbiology SC Microbiology GA CX4MI UT WOS:000365674600001 ER PT B AU Sonis, ST AF Sonis, Stephen T. BE Lacouture, ME TI Oral Mucosal Complications of Cancer Therapy SO DERMATOLOGIC PRINCIPLES AND PRACTICE IN ONCOLOGY: CONDITIONS OF THE SKIN, HAIR, AND NAILS IN CANCER PATIENTS LA English DT Article; Book Chapter ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; HERPES-SIMPLEX-VIRUS; DOUBLE-BLIND; INDUCED MUCOSITIS; CONTROLLED-TRIAL; SUPPORTIVE CARE; SCORING SYSTEM; CLINICAL-TRIAL; RISK-FACTORS C1 [Sonis, Stephen T.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sonis, Stephen T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sonis, Stephen T.] Harvard Univ, Sch Dent Med, Oral Med, Boston, MA 02115 USA. RP Sonis, ST (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 49 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-59063-8; 978-0-470-62188-2 PY 2014 BP 89 EP 99 PG 11 WC Oncology; Dermatology SC Oncology; Dermatology GA BD7EO UT WOS:000362961900010 ER PT S AU Belz, J Kumar, R Markovic, S Niedre, M Sridhar, S Nguyen, P Niedre, M DAmico, A Makrigiorgos, M Cormack, R AF Belz, Jodi Kumar, Rajiv Markovic, Stacey Niedre, Mark Sridhar, Srinivas Nguyen, Paul Niedre, Mark DAmico, Anthony Makrigiorgos, Mike Cormack, Robert GP IEEE TI Localized tumor delivery of radiosensitizers and chemotherapeutics using 'INCeRT' implants SO 2014 40TH ANNUAL NORTHEAST BIOENGINEERING CONFERENCE (NEBEC) SE Annual IEEE Northeast Bioengineering Conference LA English DT Proceedings Paper CT 40th Annual Northeast Bioengineering Conference (NEBEC) CY APR 25-27, 2014 CL Boston, MA SP Northeastern Univ, Coll Engn, EMB, Biomed Engn Soc, Northeastern Univ, Dept Bioengineering, Northeastern Univ, Dept Chem Engn, Carl Zeiss Microscopy, Northeastern Univ, Dept Elect & Comp Engn, Northeastern Univ, Dept Mech & Ind Engn, ACS Synthet Biol, Merrimach Pharmaceuiticals DE nanoparticle; local chemotherapy; brachytherapy spacers; prostate cancer; spacer AB Systemic chemotherapy is often used with radiation therapy in the management of prostate cancer, but leads to severe systemic toxicities. We have introduced a new modality of loco-regional chemoradiation therapy termed in-situ image guided radiation therapy (BIS-IGRT) that offers the potential to deliver planned, localized and sustained delivery of chemotherapy agent, without systemic toxicities, as part of routine minimally invasive image guided radiation therapy procedures. Such image guided chemoradiation therapy replaces inert spacers with no therapeutic impact currently used in brachytherapy, with drug eluting spacers that provide the same spatial benefit with the added localized chemotherapeutic. This new therapeutic modality requires characterization of the drug distribution produced by implantable drug eluters. This work presents imaging based means to measure and compare temporal and spatial properties of diffusion distributions around spacers loaded with multisized dye-doped nanoparticles or with free dye. The spacer with optimal diffusive properties was then loaded with chemotherapeutics and inserted intratumorally for efficacy of the local chemotherapy versus the standard systemic dosing. C1 [Belz, Jodi; Kumar, Rajiv; Markovic, Stacey; Niedre, Mark; Sridhar, Srinivas] Northeastern Univ, Boston, MA 02115 USA. [Nguyen, Paul; Niedre, Mark; DAmico, Anthony; Makrigiorgos, Mike; Cormack, Robert] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nguyen, Paul; Niedre, Mark; DAmico, Anthony; Makrigiorgos, Mike; Cormack, Robert] Brigham Womens Hosp, Boston, MA USA. RP Belz, J (reprint author), Northeastern Univ, Boston, MA 02115 USA. 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 0277-1063 BN 978-1-4799-3728-8 J9 NORTHEAST BIOENGIN C PY 2014 PG 2 WC Engineering, Biomedical SC Engineering GA BD8LQ UT WOS:000364054600028 ER PT S AU Bilgic, B Cauley, SF Fan, AP Polimeni, JR Wald, LL Setsompop, K Gagoski, BA Grant, PE AF Bilgic, Berkin Cauley, Stephen F. Fan, Audrey P. Polimeni, Jonathan R. Wald, Lawrence L. Setsompop, Kawin Gagoski, Borjan A. Grant, P. Ellen GP IEEE TI Wave-CAIPI Enables Highly Accelerated 3D MRI SO 2014 40TH ANNUAL NORTHEAST BIOENGINEERING CONFERENCE (NEBEC) SE Annual IEEE Northeast Bioengineering Conference LA English DT Proceedings Paper CT 40th Annual Northeast Bioengineering Conference (NEBEC) CY APR 25-27, 2014 CL Boston, MA SP Northeastern Univ, Coll Engn, EMB, Biomed Engn Soc, Northeastern Univ, Dept Bioengineering, Northeastern Univ, Dept Chem Engn, Carl Zeiss Microscopy, Northeastern Univ, Dept Elect & Comp Engn, Northeastern Univ, Dept Mech & Ind Engn, ACS Synthet Biol, Merrimach Pharmaceuiticals DE Accelerated MRI; Parallel Imaging; Image Reconstruction ID GRAPPA AB We introduce Wave-CAIPI acquisition-reconstruction technique to accelerate 3D MR Imaging by an order of magnitude, with negligible noise amplification and image artifact penalties. Wave-CAIPI involves playing sinusoidal G(y) and G(z) gradients during the readout of each phase encoding line while modifying the phase encoding strategy to incur slice shifts as in 2D-CAIPI. This combination spreads out aliasing due to data undersampling evenly in all spatial directions, thereby taking full advantage of 3D coil sensitivity distribution of the receiver coil. By expressing the voxel spreading effect as a convolution in image space, an efficient reconstruction scheme that recovers the undersampled data without data gridding is proposed. Wave-CAIPI enables full-brain gradient echo (GRE) acquisition in 2.3 minutes with 1 mm isotropic voxel size and R=3x3 acceleration, and yields maximum g-factors (noise amplification) of 1.08 at 3T, and 1.05 at 7T. Relative to state of the art accelerated imaging methods, this is a factor of 2 reduction in maximum g-factor at 3T and 7T. C1 [Bilgic, Berkin; Cauley, Stephen F.; Fan, Audrey P.; Polimeni, Jonathan R.; Wald, Lawrence L.; Setsompop, Kawin] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Gagoski, Borjan A.; Grant, P. Ellen] Boston Childrens Hosp, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA USA. RP Bilgic, B (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RI Wald, Lawrence/D-4151-2009 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 0277-1063 BN 978-1-4799-3728-8 J9 NORTHEAST BIOENGIN C PY 2014 PG 2 WC Engineering, Biomedical SC Engineering GA BD8LQ UT WOS:000364054600032 ER PT S AU Tandon, V Kang, WS McKenna, MJ Kujawa, SG Sewell, WF Kim, E Spencer, AJ Pararas, EEL Mescher, MJ Fiering, J Borenstein, JT AF Tandon, Vishal Kang, Woo Seok McKenna, Michael J. Kujawa, Sharon G. Sewell, William F. Kim, Ernest Spencer, Abigail J. Pararas, Erin E. L. Mescher, Mark J. Fiering, Jason Borenstein, Jeffrey T. GP IEEE TI An Inner-Ear Drug Delivery Platform with Fully Integrated Control, Actuation, and Fluidics Hardware SO 2014 40TH ANNUAL NORTHEAST BIOENGINEERING CONFERENCE (NEBEC) SE Annual IEEE Northeast Bioengineering Conference LA English DT Proceedings Paper CT 40th Annual Northeast Bioengineering Conference (NEBEC) CY APR 25-27, 2014 CL Boston, MA SP Northeastern Univ, Coll Engn, EMB, Biomed Engn Soc, Northeastern Univ, Dept Bioengineering, Northeastern Univ, Dept Chem Engn, Carl Zeiss Microscopy, Northeastern Univ, Dept Elect & Comp Engn, Northeastern Univ, Dept Mech & Ind Engn, ACS Synthet Biol, Merrimach Pharmaceuiticals ID SYSTEM AB Here we report on advances toward a miniaturized, fully-integrated intracochlear drug-delivery micropump and controller. Our device is designed to be worn as a head mount for guinea-pig animal models (with the ultimate goal of generating an implantable device for humans) that delivers liquid-solubilized drug through a cannula to the inner ear. Our completed platform will have infuse-withdraw capabilities, and an integrated drug reservoir. Here we present experimental data demonstrating the performance of a simplified version of the device, which has no drug reservoir and is operated only in infusion mode (though it is capable of withdrawing fluid as well). We show that our device successfully delivers the desired infusion profile in a guinea pig model. C1 [Tandon, Vishal; Kang, Woo Seok; McKenna, Michael J.; Kujawa, Sharon G.; Sewell, William F.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Kim, Ernest; Spencer, Abigail J.; Pararas, Erin E. L.; Mescher, Mark J.; Fiering, Jason; Borenstein, Jeffrey T.] Charles Stark Draper Labs, Cambridge, MA USA. RP Tandon, V (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM vtandon@draper.com; jborenstein@draper.com NR 5 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0277-1063 BN 978-1-4799-3728-8 J9 NORTHEAST BIOENGIN C PY 2014 PG 2 WC Engineering, Biomedical SC Engineering GA BD8LQ UT WOS:000364054600255 ER PT S AU Yildirim, M Ferhanglu, O Ben-Yakar, A Durr, N AF Yildirim, Murat Ferhanglu, Onur Ben-Yakar, Adela Durr, Nicholas GP IEEE TI Maximum Imaging Depth Improvement with Third-Harmonic Generation Microscopy in Turbid Tissues SO 2014 40TH ANNUAL NORTHEAST BIOENGINEERING CONFERENCE (NEBEC) SE Annual IEEE Northeast Bioengineering Conference LA English DT Proceedings Paper CT 40th Annual Northeast Bioengineering Conference (NEBEC) CY APR 25-27, 2014 CL Boston, MA SP Northeastern Univ, Coll Engn, EMB, Biomed Engn Soc, Northeastern Univ, Dept Bioengineering, Northeastern Univ, Dept Chem Engn, Carl Zeiss Microscopy, Northeastern Univ, Dept Elect & Comp Engn, Northeastern Univ, Dept Mech & Ind Engn, ACS Synthet Biol, Merrimach Pharmaceuiticals DE nonlinear microscopy; ultrafast lasers; two-photon microscopy; third-harmonic generation microscopy; turbid tissue; vocal fold scarring AB Vocal fold scarring is one of the major cause of voice disorders yet there is no reliable treatment. We hypothesized to solve this problem by creating sub-epithelial voids to localize biomaterials to restore the pliability of scarred vocal folds. In order to guide this precise surgery, there is a need for performing deep tissue imaging. Here, we present an ex-vivo study to investigate maximum imaging depth improvement of third-harmonic generation (THG) microscopy in a turbid tissue. We observed 2.5 times improvement with THG microscopy at 1552 nm wavelength compared to two-photon microscopy at 776 nm. C1 [Yildirim, Murat; Ferhanglu, Onur; Ben-Yakar, Adela] Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA. [Durr, Nicholas] Harvard Univ, Sch, Wellman Ctr Photomed, Boston, MA 02115 USA. [Durr, Nicholas] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Yildirim, M (reprint author), Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA. EM ben-yakar@mail.utexas.edu NR 10 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0277-1063 BN 978-1-4799-3728-8 J9 NORTHEAST BIOENGIN C PY 2014 PG 2 WC Engineering, Biomedical SC Engineering GA BD8LQ UT WOS:000364054600289 ER PT B AU King, DR Hwabejire, JO AF King, David R. Hwabejire, John O. BE Cohn, SM Dolich, MO TI Complications of Acute Fluid Loss and Replacement SO COMPLICATIONS IN SURGERY AND TRAUMA, 2ND EDITION LA English DT Article; Book Chapter ID CRITICALLY-ILL PATIENTS; LACTATED RINGERS SOLUTION; RISK SURGICAL-PATIENTS; ABDOMINAL COMPARTMENT SYNDROME; OXYGEN DELIVERY; SEPTIC SHOCK; HEMORRHAGIC-SHOCK; RANDOMIZED-TRIAL; BASE DEFICIT; IMMEDIATE APOPTOSIS C1 [King, David R.; Hwabejire, John O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Acute Care Surg & Surg Crit Care, Boston, MA 02138 USA. RP King, DR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Acute Care Surg & Surg Crit Care, Boston, MA 02138 USA. NR 56 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 978-1-4822-0887-0; 978-1-4822-0886-3 PY 2014 BP 59 EP 68 D2 10.1201/b16377 PG 10 WC Surgery SC Surgery GA BD6GT UT WOS:000362207100010 ER PT B AU Boros, E Marquez, BV Ikotun, OF Lapi, SE Ferreira, CL AF Boros, Eszter Marquez, Bernadette V. Ikotun, Oluwatayo F. Lapi, Suzanne E. Ferreira, Cara L. BE Storr, T TI Coordination Chemistry and Ligand Design in the Development of Metal Based Radiopharmaceuticals SO LIGAND DESIGN IN MEDICINAL INORGANIC CHEMISTRY LA English DT Article; Book Chapter ID POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO EVALUATION; BIOLOGICAL EVALUATION; BIFUNCTIONAL CHELATOR; CRYSTAL-STRUCTURES; NO-CARRIER; THERAPEUTIC RADIOPHARMACEUTICALS; TECHNETIUM RADIOPHARMACEUTICALS; TETRAAZAMACROCYCLIC COMPLEXES; STRUCTURAL-CHARACTERIZATION C1 [Boros, Eszter] Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Marquez, Bernadette V.; Ikotun, Oluwatayo F.; Lapi, Suzanne E.] Washington Univ, Dept Radiol, St Louis, MO 63110 USA. [Ferreira, Cara L.] Nordion, Vancouver, BC V6T 2A3, Canada. RP Boros, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. NR 173 TC 0 Z9 0 U1 2 U2 3 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-69791-7; 978-1-118-48852-2 PY 2014 BP 47 EP 79 D2 10.1002/9781118697191 PG 33 WC Chemistry, Medicinal; Chemistry, Inorganic & Nuclear SC Pharmacology & Pharmacy; Chemistry GA BD6FH UT WOS:000362174800003 ER PT B AU Potter, MP Hwang, S Bostic, JQ AF Potter, Mona Patel Hwang, Soonjo Bostic, Jeff Q. BE Reece, RM Hanson, RF Sargent, J TI The Abused Student Cornered School Bullying amidst Trauma SO TREATMENT OF CHILD ABUSE: COMMON GROUND FOR MENTAL HEALTH, MEDICAL, AND LEGAL PRACTITIONERS, 2ND EDITION LA English DT Article; Book Chapter ID CHILDRENS PEER GROUPS; POLY-VICTIMIZATION; PARENTAL MALTREATMENT; MIDDLE SCHOOL; ADOLESCENTS; HEALTH; EMOTION; PROGRAM; RISK; INTERVENTION C1 [Potter, Mona Patel] McLean Hosp, Child & Adolescent Psychiat, Belmont, MA 02178 USA. [Potter, Mona Patel] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Hwang, Soonjo] Massachusetts Gen Hosp, NIH, NIMH, Dept Psychiat, Boston, MA 02114 USA. [Bostic, Jeff Q.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Bostic, Jeff Q.] Massachusetts Gen Hosp, Sch Psychiat, Boston, MA 02114 USA. [Bostic, Jeff Q.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Potter, MP (reprint author), McLean Hosp, Child & Adolescent Psychiat, 115 Mill St, Belmont, MA 02178 USA. NR 55 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA 2715 N CHARLES ST, BALTIMORE, MD 21218-4319 USA BN 978-1-4214-1273-3; 978-1-4214-1274-0; 978-1-4214-1272-6 PY 2014 BP 139 EP 147 PG 9 WC Public, Environmental & Occupational Health; Medicine, Legal SC Public, Environmental & Occupational Health; Legal Medicine GA BD6NU UT WOS:000362429500016 ER PT B AU Amstadter, AB Dunn, EC Brown, RC Berenz, EC Nugent, NR AF Amstadter, Ananda B. Dunn, Erin C. Brown, Ruth C. Berenz, Erin C. Nugent, Nicole R. BE Reece, RM Hanson, RF Sargent, J TI Treatment Implications of Gene-Environment Interplay in Childhood Trauma SO TREATMENT OF CHILD ABUSE: COMMON GROUND FOR MENTAL HEALTH, MEDICAL, AND LEGAL PRACTITIONERS, 2ND EDITION LA English DT Article; Book Chapter ID POSTTRAUMATIC-STRESS-DISORDER; SEROTONIN TRANSPORTER GENE; NATIONAL COMORBIDITY SURVEY; MAJOR DEPRESSIVE DISORDER; PROMOTER VARIANT 5-HTTLPR; LINKED POLYMORPHIC REGION; GENOME-WIDE ASSOCIATION; EARLY-LIFE STRESS; X ENVIRONMENT; POPULATION STRATIFICATION C1 [Amstadter, Ananda B.; Brown, Ruth C.; Berenz, Erin C.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23284 USA. [Dunn, Erin C.] Harvard Univ, Sch Med,Broad Inst Harvard & MIT, Dept Psychiat,Massachusetts Gen Hosp,Stanley Ctr, Psychiat & Neurodev Genet Unit,Ctr Human Genet Re, Boston, MA 02115 USA. [Nugent, Nicole R.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. RP Amstadter, AB (reprint author), Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23284 USA. NR 132 TC 0 Z9 0 U1 3 U2 3 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA 2715 N CHARLES ST, BALTIMORE, MD 21218-4319 USA BN 978-1-4214-1273-3; 978-1-4214-1274-0; 978-1-4214-1272-6 PY 2014 BP 323 EP 346 PG 24 WC Public, Environmental & Occupational Health; Medicine, Legal SC Public, Environmental & Occupational Health; Legal Medicine GA BD6NU UT WOS:000362429500035 ER PT B AU Irizarry, RA AF Irizarry, Rafael A. BE Lin, X Genest, C Banks, DL Molenberghs, G Scott, DW Wang, JL TI The bright future of applied statistics SO PAST, PRESENT, AND FUTURE OF STATISTICAL SCIENCE LA English DT Article; Book Chapter ID PROBE LEVEL C1 [Irizarry, Rafael A.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Irizarry, Rafael A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Irizarry, RA (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. NR 9 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 978-1-4822-0498-8; 978-1-4822-0496-4 PY 2014 BP 171 EP 176 D2 10.1201/b16720 PG 6 WC Education, Scientific Disciplines; History & Philosophy Of Science; Statistics & Probability SC Education & Educational Research; History & Philosophy of Science; Mathematics GA BD5RD UT WOS:000361750600017 ER PT J AU Spurdle, AB Couch, FJ Parsons, MT McGuffog, L Barrowdale, D Bolla, MK Wang, Q Healey, S Schmutzler, RK Wappenschmidt, B Rhiem, K Hahnen, E Engel, C Meindl, A Ditsch, N Arnold, N Plendl, H Niederacher, D Sutter, C Wang-Gohrke, S Steinemann, D Preisler-Adams, S Kast, K Varon-Mateeva, R Ellis, S Frost, D Platte, R Perkins, J Evans, DG Izatt, L Eeles, R Adlard, J Davidson, R Cole, T Scuvera, G Manoukian, S Bonanni, B Mariette, F Fortuzzi, S Viel, A Pasini, B Papi, L Varesco, L Balleine, R Nathanson, KL Domchek, SM Offitt, K Jakubowska, A Lindor, N Thomassen, M Jensen, UB Rantala, J Borg, A Andrulis, IL Miron, A Hansen, TVO Caldes, T Neuhausen, SL Toland, AE Nevanlinna, H Montagna, M Garber, J Godwin, AK Osorio, A Factor, RE Terry, MB Rebbeck, TR Karlan, BY Southey, M Rashid, MU Tung, N Pharoah, PDP Blows, FM Dunning, AM Provenzano, E Hall, P Czene, K Schmidt, MK Broeks, A Cornelissen, S Verhoef, S Fasching, PA Beckmann, MW Ekici, AB Slamon, DJ Bojesen, SE Nordestgaard, BG Nielsen, SF Flyger, H Chang-Claude, J Flesch-Janys, D Rudolph, A Seibold, P Aittomaki, K Muranen, TA Heikkila, P Blomqvist, C Figueroa, J Chanock, SJ Brinton, L Lissowska, J Olson, JE Pankratz, VS John, EM Whittemore, AS West, DW Hamann, U Torres, D Ulmer, HU Rudiger, T Devilee, P Tollenaar, RAEM Seynaeve, C Van Asperen, CJ Eccles, DM Tapper, WJ Durcan, L Jones, L Peto, J dos-Santos-Silva, I Fletcher, O Johnson, N Dwek, M Swann, R Bane, AL Glendon, G Mulligan, AM Giles, GG Milne, RL Baglietto, L McLean, C Carpenter, J Clarke, C Scott, R Brauch, H Bruning, T Ko, YD Cox, A Cross, SS Reed, MWR Lubinski, J Jaworska-Bieniek, K Durda, K Gronwald, J Dork, T Bogdanova, N Park-Simon, TW Hillemanns, P Haiman, CA Henderson, BE Schumacher, F Le Marchand, L Burwinkel, B Marme, F Surovy, H Yang, R Anton-Culver, H Ziogas, A Hooning, MJ Collee, JM Martens, JWM Tilanus-Linthorst, MMA Brenner, H Dieffenbach, AK Arndt, V Stegmaier, C Winqvist, R Pylkas, K Jukkola-Vuorinen, A Grip, M Lindblom, A Margolin, S Joseph, V Robson, M Rau-Murthy, R Gonzalez-Neira, A Arias, JI Zamora, P Benitez, J Mannermaa, A Kataja, V Kosma, VM Hartikainen, JM Peterlongo, P Zaffaroni, D Barile, M Capra, F Radice, P Teo, SH Easton, DF Antoniou, AC Chenevix-Trench, G Goldgar, DE AF Spurdle, Amanda B. Couch, Fergus J. Parsons, Michael T. McGuffog, Lesley Barrowdale, Daniel Bolla, Manjeet K. Wang, Qin Healey, Sue Schmutzler, Rita Katharina Wappenschmidt, Barbara Rhiem, Kerstin Hahnen, Eric Engel, Christoph Meindl, Alfons Ditsch, Nina Arnold, Norbert Plendl, Hansjoerg Niederacher, Dieter Sutter, Christian Wang-Gohrke, Shan Steinemann, Doris Preisler-Adams, Sabine Kast, Karin Varon-Mateeva, Raymonda Ellis, Steve Frost, Debra Platte, Radka Perkins, Jo Evans, D. Gareth Izatt, Louise Eeles, Ros Adlard, Julian Davidson, Rosemarie Cole, Trevor Scuvera, Giulietta Manoukian, Siranoush Bonanni, Bernardo Mariette, Frederique Fortuzzi, Stefano Viel, Alessandra Pasini, Barbara Papi, Laura Varesco, Liliana Balleine, Rosemary Nathanson, Katherine L. Domchek, Susan M. Offitt, Kenneth Jakubowska, Anna Lindor, Noralane Thomassen, Mads Jensen, Uffe Birk Rantala, Johanna Borg, Ake Andrulis, Irene L. Miron, Alexander Hansen, Thomas V. O. Caldes, Trinidad Neuhausen, Susan L. Toland, Amanda E. Nevanlinna, Heli Montagna, Marco Garber, Judy Godwin, Andrew K. Osorio, Ana Factor, Rachel E. Terry, Mary B. Rebbeck, Timothy R. Karlan, Beth Y. Southey, Melissa Rashid, Muhammad Usman Tung, Nadine Pharoah, Paul D. P. Blows, Fiona M. Dunning, Alison M. Provenzano, Elena Hall, Per Czene, Kamila Schmidt, Marjanka K. Broeks, Annegien Cornelissen, Sten Verhoef, Senno Fasching, Peter A. Beckmann, Matthias W. Ekici, Arif B. Slamon, Dennis J. Bojesen, Stig E. Nordestgaard, Borge G. Nielsen, Sune F. Flyger, Henrik Chang-Claude, Jenny Flesch-Janys, Dieter Rudolph, Anja Seibold, Petra Aittomaki, Kristiina Muranen, Taru A. Heikkila, Paivi Blomqvist, Carl Figueroa, Jonine Chanock, Stephen J. Brinton, Louise Lissowska, Jolanta Olson, Janet E. Pankratz, Vernon S. John, Esther M. Whittemore, Alice S. West, Dee W. Hamann, Ute Torres, Diana Ulmer, Hans Ulrich Rudiger, Thomas Devilee, Peter Tollenaar, Robert A. E. M. Seynaeve, Caroline Van Asperen, Christi J. Eccles, Diana M. Tapper, William J. Durcan, Lorraine Jones, Louise Peto, Julian dos-Santos-Silva, Isabel Fletcher, Olivia Johnson, Nichola Dwek, Miriam Swann, Ruth Bane, Anita L. Glendon, Gord Mulligan, Anna M. Giles, Graham G. Milne, Roger L. Baglietto, Laura McLean, Catriona Carpenter, Jane Clarke, Christine Scott, Rodney Brauch, Hiltrud Bruning, Thomas Ko, Yon-Dschun Cox, Angela Cross, Simon S. Reed, Malcolm W. R. Lubinski, Jan Jaworska-Bieniek, Katarzyna Durda, Katarzyna Gronwald, Jacek Dork, Thilo Bogdanova, Natalia Park-Simon, Tjoung-Won Hillemanns, Peter Haiman, Christopher A. Henderson, Brian E. Schumacher, Fredrick Le Marchand, Loic Burwinkel, Barbara Marme, Frederik Surovy, Harald Yang, Rongxi Anton-Culver, Hoda Ziogas, Argyrios Hooning, Maartje J. Collee, J. Margriet Martens, John W. M. Tilanus-Linthorst, Madeleine M. A. Brenner, Hermann Dieffenbach, Aida Karina Arndt, Volke Stegmaier, Christa Winqvist, Robert Pylkas, Katri Jukkola-Vuorinen, Arja Grip, Mervi Lindblom, Annika Margolin, Sara Joseph, Vijai Robson, Mark Rau-Murthy, Rohini Gonzalez-Neira, Anna Arias, Jose Ignacio Zamora, Pilar Benitez, Javier Mannermaa, Arto Kataja, Vesa Kosma, Veli-Matti Hartikainen, Jaana M. Peterlongo, Paolo Zaffaroni, Daniela Barile, Monica Capra, Fabio Radice, Paolo Teo, Soo H. Easton, Douglas F. Antoniou, Antonis C. Chenevix-Trench, Georgia Goldgar, David E. CA ABCTB Investigators EMBRACE Group GENICA Network HEBON Group kConFab Investigators TI Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia SO BREAST CANCER RESEARCH LA English DT Article ID DNA-SEQUENCE VARIANTS; UNKNOWN CLINICAL-SIGNIFICANCE; ESTROGEN-RECEPTOR; GERMLINE MUTATIONS; BASAL PHENOTYPE; BRCA1-MUTATION CARRIERS; ASSOCIATION CONSORTIUM; PATHOLOGICAL FEATURES; OVARIAN CANCERS; TUMOR PATHOLOGY AB Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of mutation status by histopathological markers were derived using a Mantel-Haenszel approach. Results: ER-positive phenotype negatively predicted BRCA1 mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative grade 3 histopathology was more predictive of positive BRCA1 mutation status in women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3 phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3 features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was highly predictive of BRCA1 mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive BRCA2 mutation status in women 50 years or older (LR = 1.79 (1.42 to 2.24)). Conclusions: These results refine likelihood-ratio estimates for predicting BRCA1 and BRCA2 mutation status by using commonly measured histopathological features. Age at diagnosis is an important variable for most analyses, and grade is more informative than ER status for BRCA2 mutation carrier prediction. The estimates will improve BRCA1 and BRCA2 variant classification and inform patient mutation testing and clinical management. C1 [Spurdle, Amanda B.; Parsons, Michael T.; Healey, Sue; Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Dept Genet & Computat Biol, Brisbane, Qld 4006, Australia. [Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [McGuffog, Lesley; Barrowdale, Daniel; Bolla, Manjeet K.; Wang, Qin; Ellis, Steve; Frost, Debra; Platte, Radka; Perkins, Jo; Easton, Douglas F.; Antoniou, Antonis C.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England. [Wang, Qin; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge CB2 1TN, England. [Schmutzler, Rita Katharina; Wappenschmidt, Barbara; Rhiem, Kerstin; Hahnen, Eric] Univ Cologne, Ctr Hereditary Breast & Ovarian Canc, CIO, Cologne, Germany. [Schmutzler, Rita Katharina; Wappenschmidt, Barbara; Rhiem, Kerstin; Hahnen, Eric] Univ Cologne, CMMC, Fac Med, Cologne, Germany. [Schmutzler, Rita Katharina; Wappenschmidt, Barbara; Rhiem, Kerstin; Hahnen, Eric] Univ Hosp Cologne, Cologne, Germany. [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04107 Leipzig, Germany. [Meindl, Alfons] Tech Univ Munich, Div Gynaecol & Obstet, D-81675 Munich, Germany. [Ditsch, Nina] Univ Munich, Dept Gynaecol & Obstet, D-80337 Munich, Germany. [Plendl, Hansjoerg] Univ Kiel, Inst Human Genet, Univ Hosp Schleswig Holstein, Kiel, Germany. [Plendl, Hansjoerg] Univ Med Ctr Schleswig Holstein, Kiel, Germany. [Niederacher, Dieter] Univ Dusseldorf, Univ Hosp Dusseldorf, Dept Gynaecol & Obstet, Dusseldorf, Germany. [Sutter, Christian] Univ Hosp Heidelberg, Inst Human Genet, D-69120 Heidelberg, Germany. [Wang-Gohrke, Shan] Univ Hosp Ulm, Dept Gynaecol & Obstet, D-89081 Ulm, Germany. [Steinemann, Doris] Hannover Med Sch, Inst Cell & Mol Pathol, Hannover, Germany. [Preisler-Adams, Sabine] Univ Munster, Inst Human Genet, Munster, Germany. [Kast, Karin] Tech Univ Dresden, Dept Gynecol & Obstet, Univ Hosp Carl Gustav Carus, Dresden, Germany. [Varon-Mateeva, Raymonda] Campus Virchov Klinikum, Inst Human Genet, Charite Berlin, Germany. [Evans, D. Gareth] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Genet Med, Manchester, Lancs, England. [Izatt, Louise] Guys & St Thomas NHS Fdn Trust, Clin Genet, London, England. [Eeles, Ros] Inst Canc Res, Oncogenet Team, Sutton, Surrey, England. [Eeles, Ros] Royal Marsden NHS Fdn Trust, Sutton, Surrey, England. [Adlard, Julian] Chapel Allerton Hosp, Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England. [Davidson, Rosemarie] Southern Gen Hosp, Dept Clin Genet, Glasgow G51 4TF, Lanark, Scotland. [Cole, Trevor] Birmingham Womens Hosp Healthcare NHS Trust, West Midlands Reg Genet Serv, Birmingham, W Midlands, England. [Scuvera, Giulietta; Manoukian, Siranoush; Zaffaroni, Daniela] Fdn IRCCS Ist Nazl Tumori INT, Unit Med Genet, Dept Prevent & Predict Med, I-20133 Milan, Italy. [Bonanni, Bernardo; Barile, Monica] IEO, Div Canc Prevent & Genet, I-20141 Milan, Italy. [Mariette, Frederique; Fortuzzi, Stefano; Peterlongo, Paolo; Capra, Fabio] Fdn Ist FIRC Oncol Mol, IFOM, I-20139 Milan, Italy. [Mariette, Frederique; Fortuzzi, Stefano; Capra, Fabio] Cogentech Canc Genet Test Lab, I-20139 Milan, Italy. [Viel, Alessandra] CRO Aviano Natl Canc Inst, Div Expt Oncol 1, I-33081 Aviano, PN, Italy. [Pasini, Barbara] Univ Turin, Dept Med Sci, I-10126 Turin, Italy. [Pasini, Barbara] AOU Citta Salute & Sci, I-10126 Turin, Italy. [Papi, Laura] Univ Florence, Unit Med Genet, Dept Biomed Expt & Clin Sci, I-50139 Florence, Italy. [Varesco, Liliana] IRCCS AOU San Martino IST Ist Nazl Ric Canc, Unit Hereditary Canc, I-16132 Genoa, Italy. [Balleine, Rosemary] Univ Sydney, Western Sydney & Nepean Blue Mt Local Hlth Dist, Westmead Millennium Inst Med Res, Westmead, NSW 2145, Australia. [Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy R.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Offitt, Kenneth; Joseph, Vijai; Robson, Mark; Rau-Murthy, Rohini] Mem Sloan Kettering Canc Ctr, Clin Genet Serv, Dept Med, New York, NY 10021 USA. [Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Gronwald, Jacek] Pomeranian Med Univ, Dept Genet & Pathol, PL-70115 Szczecin, Poland. [Lindor, Noralane] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ USA. [Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, Odense C, Denmark. [Jensen, Uffe Birk] Aarhus Univ Hosp, Dept Clin Genet, Aarhus N, Denmark. [Rantala, Johanna] Karolinska Univ Hosp L5 03, Dept Clin Genet, S-17176 Stockholm, Sweden. [Borg, Ake] Lund Univ, Dept Oncol, Clin Sci, Lund, Sweden. [Borg, Ake] Skane Univ Hosp, Lund, Sweden. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. [Andrulis, Irene L.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Miron, Alexander] Case Western Reserve Univ, Dept Genet & Genome Serv, Sch Med, Cleveland, OH 44106 USA. [Hansen, Thomas V. O.] Univ Copenhagen Hosp, Rigshosp, Ctr Genom Med, DK-2100 Copenhagen, Denmark. [Caldes, Trinidad] Hosp Clin San Carlos, Mol Oncol Lab, IdISSC, Madrid, Spain. [Neuhausen, Susan L.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. [Toland, Amanda E.] Ohio State Univ, Div Human Canc Genet, Dept Internal Med, Comprehens Canc Ctr, Columbus, OH USA. [Toland, Amanda E.] Ohio State Univ, Div Human Canc Genet, Dept Mol Virol Immunol & Med Genet, Comprehens Canc Ctr, Columbus, OH USA. [Nevanlinna, Heli; Muranen, Taru A.] Univ Helsinki, Dept Obstet & Gynecol, FI-00029 Helsinki, Finland. [Nevanlinna, Heli; Muranen, Taru A.] Univ Helsinki, Cent Hosp, FI-00029 Helsinki, Finland. [Montagna, Marco] Ist Oncol Veneto IOV IRCCS, Immunol & Mol Oncol Unit, Padua, Italy. [Garber, Judy] Dana Farber Canc Inst, Boston, MA USA. [Godwin, Andrew K.] Univ Kansas, Dept Pathol & Lab Med, Med Ctr, Kansas City, KS USA. [Osorio, Ana; Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Human Canc Genet Program, Madrid 28029, Spain. [Osorio, Ana] Biomed Network Rare Dis CIBERER, Madrid, Spain. [Factor, Rachel E.] Univ Utah, Dept Pathol, Hlth Sci Ctr, Salt Lake City, UT 84132 USA. [Terry, Mary B.] Columbia Univ, Dept Epidemiol, New York, NY USA. [Karlan, Beth Y.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA USA. [Southey, Melissa] Univ Melbourne, Genet Epidemiol Lab, Dept Pathol, Parkville, Vic, Australia. [Rashid, Muhammad Usman; Hamann, Ute; Torres, Diana] Deutsch Krebsforschungszentrum DKFZ, Mol Genet Breast Canc, D-69120 Heidelberg, Germany. [Rashid, Muhammad Usman] Shaukat Khanum Mem Canc Hosp & Res Ctr SKMCH & RC, Dept Basic Sci, Johar, Pakistan. [Pharoah, Paul D. P.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England. [Blows, Fiona M.; Dunning, Alison M.; Provenzano, Elena] Univ Cambridge, Dept Oncol, Cambridge CB2 1TN, England. [Hall, Per; Czene, Kamila] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Schmidt, Marjanka K.; Broeks, Annegien; Cornelissen, Sten; Verhoef, Senno] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands. [Fasching, Peter A.; Slamon, Dennis J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Fasching, Peter A.; Beckmann, Matthias W.] Univ Erlangen Nurnberg, Comprehens Canc Ctr Erlangen EMN, Univ Breast Ctr Franconia, Univ Hosp Erlangen,Dept Gynecol & Obstet, D-91054 Erlangen, Germany. [Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Univ Hosp Erlangen, D-91054 Erlangen, Germany. [Slamon, Dennis J.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Bojesen, Stig E.; Nordestgaard, Borge G.; Nielsen, Sune F.] Univ Copenhagen Hosp, Copenhagen Gen Populat Study, Herlev Hosp, DK-2730 Herlev, Denmark. [Bojesen, Stig E.; Nordestgaard, Borge G.; Nielsen, Sune F.] Univ Copenhagen Hosp, Dept Clin Biochem, Herlev Hosp, DK-2730 Herlev, Denmark. [Bojesen, Stig E.; Nordestgaard, Borge G.] Univ Copenhagen, Fac Hlth & Med Sci, DK-2200 Copenhagen N, Denmark. [Flyger, Henrik] Univ Copenhagen Hosp, Dept Breast Surg, Herlev Hosp, DK-2730 Herlev, Denmark. [Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany. [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Dept Canc Epidemiol, Clin Canc Registry, D-20246 Hamburg, Germany. [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, D-20246 Hamburg, Germany. [Aittomaki, Kristiina] Univ Helsinki, Dept Clin Genet, FI-00029 Helsinki, Hus, Finland. [Aittomaki, Kristiina; Blomqvist, Carl] Univ Helsinki, Cent Hosp, FI-00029 Helsinki, Hus, Finland. [Heikkila, Paivi] Univ Helsinki, Cent Hosp, Dept Pathol, FI-00029 Helsinki, Hus, Finland. [Blomqvist, Carl] Univ Helsinki, Dept Oncol, FI-00029 Helsinki, Hus, Finland. [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Olson, Janet E.; Pankratz, Vernon S.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [John, Esther M.; West, Dee W.] Canc Prevent Inst Calif, Fremont, CA 94538 USA. [John, Esther M.; Whittemore, Alice S.; West, Dee W.] Stanford Univ, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA. [Torres, Diana] Pontificia Univ Javeriana, Inst Human Genet, Bogota 11001000, DC, Colombia. [Ulmer, Hans Ulrich] Frauenklin Stadtklin Baden Baden, D-76532 Baden Baden, Germany. [Rudiger, Thomas] Stadt Klinikum Karlsruhe, Inst Pathol, D-76133 Karlsruhe, Germany. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZC Leiden, Netherlands. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Pathol, NL-2333 ZC Leiden, Netherlands. [Tollenaar, Robert A. E. M.] Leiden Univ, Med Ctr, Dept Surg Oncol, NL-2333 ZC Leiden, Netherlands. [Seynaeve, Caroline] Erasmus MC Daniel den Hoed Canc Ctr, Family Canc Clin, Dept Med Oncol, NL-3075 EA Rotterdam, Netherlands. [Van Asperen, Christi J.] Leiden Univ, Med Ctr, Dept Clin Genet, NL-2333 ZC Leiden, Netherlands. [Eccles, Diana M.; Tapper, William J.; Durcan, Lorraine] Univ Southampton, Fac Med, Southampton SO17 1BJ, Hants, England. [Jones, Louise] Queen Mary Univ London, London E1 4NS, England. [Peto, Julian; dos-Santos-Silva, Isabel] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1E 7HT, England. [Fletcher, Olivia; Johnson, Nichola] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Dwek, Miriam; Swann, Ruth] Univ Westminster, Fac Sci & Technol, Dept Mol & Appl Biosci, London W1W 6UW, England. [Bane, Anita L.] Juravinski Hosp, Dept Pathol & Mol Med, Hamilton, ON L8V 1C3, Canada. [Bane, Anita L.] McMaster Univ, Ctr Canc, Hamilton, ON L8V 1C4, Canada. [Glendon, Gord] Mt Sinai Hosp, Ontario Canc Genet Network, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Mulligan, Anna M.] Univ Hlth Network, Dept Pathol, Toronto, ON M5G 2C4, Canada. [Mulligan, Anna M.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada. [Giles, Graham G.; Milne, Roger L.; Baglietto, Laura] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3004, Australia. [Giles, Graham G.; Milne, Roger L.; Baglietto, Laura] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Melbourne, Vic 3010, Australia. [McLean, Catriona] Alfred Hosp, Anat Pathol, Melbourne, Vic 3004, Australia. [Carpenter, Jane] Univ Sydney, Westmead Millennium Inst, Australian Breast Canc Tissue Bank, Sydney, NSW 2145, Australia. [Clarke, Christine] Univ Sydney, Westmead Inst Canc Res, Sydney, NSW 2145, Australia. [Scott, Rodney] Univ Newcastle, Discipline Med Genet, Sch Biomed Sci & Pharm, Fac Hlth, Callaghan, NSW 2305, Australia. [Scott, Rodney] John Hunter Hosp, Div Genet, Hunter Area Pathol Serv, Newcastle, NSW 2305, Australia. [Brauch, Hiltrud] Univ Tubingen, D-72074 Tubingen, Germany. [Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany. [Bruning, Thomas] German Social Accident Insurance IPA, Inst Prevent & Occupat Med, D-44789 Bochum, Germany. [Ko, Yon-Dschun] Evangelische Kliniken Bonn gGmbH, D-53113 Bonn, Germany. [Cox, Angela; Reed, Malcolm W. R.] Univ Sheffield, Dept Oncol, CRUK YCR Sheffield Canc Res Ctr, Sheffield S10 2RX, S Yorkshire, England. [Cross, Simon S.] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Sheffield S10 2HQ, S Yorkshire, England. [Dork, Thilo] Hannover Med Sch, Clin Radiat Oncol, D-30625 Hannover, Germany. [Bogdanova, Natalia; Park-Simon, Tjoung-Won; Hillemanns, Peter] Hannover Med Sch, Dept Obstet & Gynaecol, D-30625 Hannover, Germany. [Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Epidemiol Program, Honolulu, HI 96813 USA. [Burwinkel, Barbara; Marme, Frederik; Surovy, Harald; Yang, Rongxi] Heidelberg Univ, Dept Obstet & Gynecol, D-69120 Heidelberg, Germany. [Burwinkel, Barbara; Surovy, Harald; Yang, Rongxi] German Canc Res Ctr, Mol Epidemiol Grp, D-69120 Heidelberg, Germany. [Marme, Frederik] Heidelberg Univ, Natl Ctr Tumor Dis, D-69120 Heidelberg, Germany. [Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA 92697 USA. [Hooning, Maartje J.; Martens, John W. M.] Erasmus Univ, Med Ctr, Dept Med Oncol, Family Canc Clin, NL-3008 AE Rotterdam, Netherlands. [Collee, J. Margriet] Erasmus Univ, Med Ctr, Dept Clin Genet, Family Canc Clin, NL-3000 CA Rotterdam, Netherlands. [Tilanus-Linthorst, Madeleine M. A.] Erasmus Univ, Med Ctr, Dept Surg Oncol, Rotterdam, Netherlands. [Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volke] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany. [Stegmaier, Christa] Saarland Canc Registry, D-66119 Saarbrucken, Germany. [Winqvist, Robert; Pylkas, Katri] Univ Oulu, NordLab Oulu Oulu Univ Hosp, Dept Clin Chem, Lab Canc Genet & Tumor Biol, FI-90220 Oulu, Finland. [Winqvist, Robert; Pylkas, Katri] Univ Oulu, NordLab Oulu Oulu Univ Hosp, Bioctr Oulu, FI-90220 Oulu, Finland. [Jukkola-Vuorinen, Arja] Univ Oulu, Oulu Univ Hosp, Dept Oncol, FI-90220 Oulu, Finland. [Grip, Mervi] Univ Oulu, Oulu Univ Hosp, Dept Surg, FI-90220 Oulu, Finland. [Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, SE-17177 Stockholm, Sweden. [Margolin, Sara] Karolinska Inst, Dept Oncol & Pathol, SE-17177 Stockholm, Sweden. [Gonzalez-Neira, Anna] Spanish Natl Canc Res Ctr CNIO, Human Genotyping CEGEN Unit, Human Canc Genet Program, Madrid 28029, Spain. [Arias, Jose Ignacio] Hosp Monte Naranco, Serv Cirugia Gen & Especialidades, Oviedo 33012, Asturias, Spain. [Zamora, Pilar] Hosp Univ La Paz, Serv Oncol Med, Madrid 28046, Spain. [Benitez, Javier] Ctr Invest Red Enfermedades Raras CIBERER, Valencia, Spain. [Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Sch Med, FI-70211 Kuopio, Finland. [Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Kuopio Univ Hosp, Imaging Ctr, Dept Clin Pathol, Kuopio 70210, Finland. [Kataja, Vesa] Kuopio Univ Hosp, Canc Ctr, Kuopio 70210, Finland. [Radice, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, I-20133 Milan, Italy. [Teo, Soo H.] Sime Darby Med Ctr, Canc Res Initiat Fdn, Selangor, Malaysia. [Teo, Soo H.] Univ Malaya, Canc Res Inst, Fac Med, Kuala Lumpur 50603, Malaysia. [Goldgar, David E.] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT 84108 USA. [Goldgar, David E.] Univ Utah, Sch Med, Huntsman Canc Inst, Salt Lake City, UT 84108 USA. [Figueroa, Jonine; Chanock, Stephen J.; Brinton, Louise] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA. RP Spurdle, AB (reprint author), QIMR Berghofer Med Res Inst, Dept Genet & Computat Biol, Brisbane, Qld 4006, Australia. EM Amanda.Spurdle@qimrberghofer.edu.au RI Brinton, Louise/G-7486-2015; Spurdle, Amanda/A-4978-2011; montagna, marco/E-2225-2012; Hartikainen, Jaana/E-6256-2015; Teo, Soo-hwang/H-2353-2014; Bruning, Thomas/G-8120-2015; Dork, Thilo/J-8620-2012; Gronwald, Jacek/A-4576-2017; Brenner, Hermann/B-4627-2017; manoukian, siranoush/E-7132-2017; OI Barrowdale, Daniel/0000-0003-1661-3939; Cross, Simon/0000-0003-2044-1754; Papi, Laura/0000-0003-4552-9517; Dunning, Alison Margaret/0000-0001-6651-7166; Cox, Angela/0000-0002-5138-1099; Giles, Graham/0000-0003-4946-9099; Evans, Gareth/0000-0002-8482-5784; Brinton, Louise/0000-0003-3853-8562; Devilee, Peter/0000-0002-8023-2009; Spurdle, Amanda/0000-0003-1337-7897; montagna, marco/0000-0002-4929-2150; Bruning, Thomas/0000-0001-9560-5464; Gronwald, Jacek/0000-0002-3643-2871; Brenner, Hermann/0000-0002-6129-1572; manoukian, siranoush/0000-0002-6034-7562; Eeles, Rosalind/0000-0002-3698-6241 FU NHMRC Senior Research Fellowship; Australian NHMRC Project [1010719]; NIH [CA128978, CA116167]; NIH specialized program of research excellence in breast cancer to the Mayo Clinic [P50 CA116201]; Breast Cancer Research Foundation; Cancer Research-UK [C12292/A11174, C1287/A10118, C1287/A12014]; European Communitys Seventh Framework Programme [223175 HEALTH-F2-2009-223175] FX Amanda Spurdle is supported by an NHMRC Senior Research Fellowship, and aspects of this research were funded by Australian NHMRC Project grant ID 1010719. This work was supported in part by NIH grants CA128978 and CA116167, an NIH specialized program of research excellence in breast cancer to the Mayo Clinic (P50 CA116201), and the Breast Cancer Research Foundation. CIMBA data management was supported by Cancer Research-UK grant C12292/A11174 and C1287/A10118. ACA is a Cancer Research-UK Senior Cancer Research Fellow. BCAC data management was funded by Cancer Research UK (C1287/A10118 and C1287/A12014) and by the European Communitys Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175). NR 54 TC 13 Z9 13 U1 4 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2014 VL 16 IS 6 AR 3419 DI 10.1186/s13058-014-0474-y PG 16 WC Oncology SC Oncology GA CB8NB UT WOS:000349885800041 PM 25857409 ER PT B AU Magidson, JF O'Cleirigh, C AF Magidson, Jessica F. O'Cleirigh, Conall BE Joska, JA Stein, DJ Grant, I TI Specifying the Mental Health Context for the Development of HIV Prevention and Treatment Interventions for Men Who Have Sex with Men SO HIV AND PSYCHIATRY SE Current Science and Clinical Practice Series LA English DT Editorial Material; Book Chapter ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; DEPRESSION CBT-AD; RISK; ADHERENCE; STIGMA; ABUSE; SKIN C1 [Magidson, Jessica F.; O'Cleirigh, Conall] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Magidson, Jessica F.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. [O'Cleirigh, Conall] Fenway Hlth, Fenway Inst, Boston, MA USA. RP Magidson, JF (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-33954-1; 978-1-118-33953-4 J9 CURR SCI CLIN PRACT PY 2014 BP 240 EP 244 D2 10.1002/9781118339503 PG 5 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BD6FG UT WOS:000362174700023 ER PT B AU Bighamian, R Reisner, AT Hahn, JO AF Bighamian, Ramin Reisner, Andrew T. Hahn, Jin-Oh GP ASME TI CLOSED-LOOP CONTROL OF FLUID RESUSCITATION VIA BLOOD VOLUME ESTIMATION SO 7TH ANNUAL DYNAMIC SYSTEMS AND CONTROL CONFERENCE, 2014, VOL 3 LA English DT Proceedings Paper CT ASME 7th Annual Dynamic Systems and Control Conference CT Research Workshop Israel Science Foundation on Infinite Products of Operators and their Applications CY OCT 22-24, 2014 CY MAY 21-24, 2012 CL San Antonio, TX CL Technion, Israel Inst Technol, Haifa, ISRAEL SP ASME, Dynam Syst & Control Div SP Technion, Ctr Math Sci HO Technion, Israel Inst Technol ID ARTERIAL PULSE PRESSURE; STROKE VOLUME; HEMODYNAMIC OPTIMIZATION; VENTRICULAR INTERACTION; MATHEMATICAL-MODEL; CONTRACTILE STATE; FILLING PRESSURE; BURN PATIENTS; RESPONSIVENESS; MANAGEMENT AB This paper presents a model-based approach to the closed-loop control of fluid resuscitation against hypovolemia. In this approach, the control system consists of a model-based blood volume estimator and a feedback controller The model-based blood volume estimator derives relative changes in the blood volume response to the augmented fluid by analyzing an arterial blood pressure waveform and the electrocardiogram. Then, the feedback controller determines the amount of fluid to be augmented by comparing targeted versus estimated relative changes in the blood volume. In this way, unlike many previous methods for fluid resuscitation based on indirect surrogate(s) of blood volume, fluid resuscitation can be directly guided by the blood volume response. This paper reports initial design of the closed-loop control system and its simulation-based evaluation in a wide range of hypovolemic and physiologic scenarios. The results suggest that the proposed closed-loop control system is very effective in resuscitation against hypovolemia: in 97 out of 100 simulated hypovolemia, the final blood volume achieved by the control system was within 10% of its optimal value. C1 [Bighamian, Ramin; Hahn, Jin-Oh] Univ Maryland, Mech Engn, College Pk, MD 20742 USA. [Reisner, Andrew T.] Massachusetts Gen Hosp, Emergency Med, Boston, MA 02142 USA. RP Bighamian, R (reprint author), Univ Maryland, Mech Engn, College Pk, MD 20742 USA. EM rbighami@umd.edu; areisner@partners.org; jhahn12@umd.edu NR 56 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 978-0-7918-4620-9 PY 2014 AR V003T46A001 PG 7 WC Automation & Control Systems; Engineering, Mechanical; Operations Research & Management Science SC Automation & Control Systems; Engineering; Operations Research & Management Science GA BD4XX UT WOS:000361167200057 ER PT J AU Quadeer, AA Louie, RHY Shekhar, K Chakraborty, AK Hsing, I McKay, MR AF Quadeer, A. A. Louie, R. H. Y. Shekhar, K. Chakraborty, A. K. Hsing, I. McKay, M. R. GP IEEE TI DISCOVERING STATISTICAL VULNERABILITIES IN HIGHLY MUTABLE VIRUSES: A RANDOM MATRIX APPROACH SO 2014 IEEE WORKSHOP ON STATISTICAL SIGNAL PROCESSING (SSP) LA English DT Proceedings Paper CT IEEE Workshop on Statistical Signal Processing (SSP) CY JUN 29-JUL 02, 2014 CL Gold Coast, AUSTRALIA SP IEEE DE Random matrices; estimation; hepatitis C virus ID HEPATITIS-C VIRUS; REPLICATION AB The advancement in fast DNA sequencing technologies has opened up new opportunities to explore a diverse set of questions in biomedical research. In this paper, we review a general method which utilizes the available sequence data to determine potential weaknesses in highly mutable viruses, and which has shown promise in the design of vaccines. A key computational part of this method employs concepts from random matrix theory to obtain a robust estimate of a large covariance matrix. We apply this general method on hepatitis C virus as an example, and verify its usefulness by linking with the existing experimental and structural data. C1 [Quadeer, A. A.; Louie, R. H. Y.; McKay, M. R.] HKUST, Dept Elect & Comp Engn, Hong Kong, Hong Kong, Peoples R China. [Shekhar, K.; Chakraborty, A. K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Shekhar, K.; Chakraborty, A. K.] Ragon Inst Massachusetts Gen Hosp & Harvard, Boston, MA 02129 USA. [Chakraborty, A. K.] MIT, Dept Phys Chem & Biol Engn, Cambridge, MA 02139 USA. [Chakraborty, A. K.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Chakraborty, A. K.] HKUST, Inst Adv Study, Kowloon, Hong Kong, Peoples R China. [Hsing, I.] HKUST, Dept Chem & Biomol Engn, Hong Kong, Hong Kong, Peoples R China. [Hsing, I.; McKay, M. R.] HKUST, Div Biomed Engn, Hong Kong, Hong Kong, Peoples R China. RP Quadeer, AA (reprint author), HKUST, Dept Elect & Comp Engn, Hong Kong, Hong Kong, Peoples R China. OI Hsing, I-Ming/0000-0002-3326-3021 NR 19 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-4975-5 PY 2014 BP 5 EP 8 PG 4 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA BD4RB UT WOS:000361019700002 ER PT S AU Plourde, J Arney, D Goldman, JM AF Plourde, Jeffrey Arney, David Goldman, Julian M. GP IEEE TI OpenICE: An Open, Interoperable Platform for Medical Cyber-Physical Systems SO 2014 ACM/IEEE INTERNATIONAL CONFERENCE ON CYBER-PHYSICAL SYSTEMS (ICCPS) SE ACM-IEEE International Conference on Cyber-Physical Systems LA English DT Proceedings Paper CT 5th ACM/IEEE International Conference on Cyber-Physical Systems (ICCPS) CY APR 14-17, 2014 CL Berlin, GERMANY SP ACM, IEEE C1 [Plourde, Jeffrey; Arney, David] Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Goldman, Julian M.] Harvard Univ, Sch Med, MGH, Boston, MA USA. RP Plourde, J (reprint author), Massachusetts Gen Hosp, Cambridge, MA 02138 USA. EM jeff@mdpnp.org; dave@mdpnp.org; JMGOLDMAN@mgh.harvard.edu NR 0 TC 5 Z9 5 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2375-8317 BN 978-1-4799-4930-4 J9 ACM IEEE INT CONF CY PY 2014 BP 221 EP 221 PG 1 WC Computer Science, Information Systems; Computer Science, Software Engineering; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BD3XU UT WOS:000360295000028 ER PT S AU Deshpande, V Primiani, A AF Deshpande, Vikram Primiani, Andrea BE Herman, JM Pawlik, TM Thomas, CR TI Pathology of Gallbladder Cancer SO BILIARY TRACT AND GALLBLADDER CANCER: A MULTIDISCIPLINARY APPROACH, 2ND EDITION SE Medical Radiology-Radiation Oncology LA English DT Article; Book Chapter ID CLINICOPATHOLOGICAL ANALYSIS; PAPILLARY CARCINOMAS; CELL CARCINOMA; BILE-DUCT; IN-SITU; BILIARY; HYPERPLASIA; MANAGEMENT; NEOPLASMS; LESIONS AB Gallbladder cancer is an uncommon cancer of gastrointestinal tract. Adenocarcinoma is the most common type of cancer to arise within the gallbladder and is typically associated with two precursor lesions: flat dysplasia and adenomas. Intracystic papillary neoplasms and mucinous cystic neoplasms are less common precursor lesions. The prognosis of patients with gallbladder carcinoma is highly dependent on tumor stage. Non-invasive and minimally invasive adenocarcinomas are typically cured with cholecystectomy and hence precise pathologic staging is critical for management and prognostication. Other less common variants of gallbladder carcinoma include adenosquamous carcinoma, squamous cell carcinoma, carcinosarcoma, and undifferentiated carcinoma and are typically associated with a worse prognosis. Neuroendocrine neoplasmas, lymphomas, and mesenchymal neoplasms of the gallbladder, as well as metastases, are extremely rare. C1 [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Primiani, Andrea] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM vdeshpande@partners.org NR 40 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0942-5373 BN 978-3-642-40558-7; 978-3-642-40557-0 J9 MED RADIOL RADIAT ON PY 2014 BP 45 EP 56 DI 10.1007/978-3-642-40558-7_3 D2 10.1007/978-3-642-40558-7 PG 12 WC Oncology; Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA BD2CP UT WOS:000358661900007 ER PT S AU Phillips, JG Wolfgang, JA Hong, TS AF Phillips, John G. Wolfgang, John A. Hong, Theodore S. BE Herman, JM Pawlik, TM Thomas, CR TI Emerging Techniques in Image-Guided Radiation Therapy and Stereotactic Body Radiation Therapy SO BILIARY TRACT AND GALLBLADDER CANCER: A MULTIDISCIPLINARY APPROACH, 2ND EDITION SE Medical Radiology-Radiation Oncology LA English DT Article; Book Chapter ID 4-DIMENSIONAL COMPUTED-TOMOGRAPHY; IMPLANTED FIDUCIAL MARKERS; ACTIVE BREATHING CONTROL; TIME TUMOR-TRACKING; ABDOMINAL COMPRESSION; RESPIRATORY MOTION; RADIOTHERAPY SBRT; NORMAL TISSUE; ORGAN MOTION; LIVER AB Locoregional recurrence is the primary failure pattern for biliary tract and gallbladder cancers. However, the use of external beam radiation therapy in the treatment for these cancers, particularly cholangiocarcinoma, has had limited efficacy historically due to the high risk of toxicity with curative doses. While a range of anatomic locations and thus dose-limiting structures exist, proximity to the duodenum, risk of biliary stricture, and radiation-induced liver disease (RILD) have posed special challenges to achieving a dose capable of preventing local recurrence or achieving cure. Over the last decade, the rapid development and integration of technologies such as advanced onboard imaging (OBI) integrated with stereotactic body radiation therapy (SBRT) have created renewed interest in the use of external beam radiation in both the adjuvant and palliative setting for these cancers. In this chapter, we review the relevant advances, particularly the growing experience with SBRT in intrahepatic cholangiocarcinoma (ICC). C1 [Phillips, John G.] Harvard Radiat Oncol Program, Boston, MA 02215 USA. [Wolfgang, John A.; Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Phillips, JG (reprint author), Harvard Radiat Oncol Program, Boston, MA 02215 USA. EM tshong1@partners.org NR 33 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0942-5373 BN 978-3-642-40558-7; 978-3-642-40557-0 J9 MED RADIOL RADIAT ON PY 2014 BP 311 EP 320 DI 10.1007/978-3-642-40558-7_21 D2 10.1007/978-3-642-40558-7 PG 10 WC Oncology; Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA BD2CP UT WOS:000358661900025 ER PT J AU Mechanick, JI Marchetti, AE Apovian, C Benchimol, AK Bisschop, PH Bolio-Galvis, A Hegazi, RA Jenkins, D Mendoza, E Sanz, ML Sheu, WHH Tatti, P Tsang, MW Hamdy, O AF Mechanick, Jeffrey I. Marchetti, Albert E. Apovian, Caroline Benchimol, Alexander Koglin Bisschop, Peter H. Bolio-Galvis, Alexis Hegazi, Refaat A. Jenkins, David Mendoza, Enrique Leon Sanz, Miguel Sheu, Wayne Huey-Herng Tatti, Patrizio Tsang, Man-Wo Hamdy, Osama BE Coles, L TI DIABETES-SPECIFIC NUTRITION ALGORITHM: A TRANSCULTURAL PROGRAM TO OPTIMIZE DIABETES AND PREDIABETES CARE SO CLINICAL NUTRITION: THE INTERFACE BETWEEN METABOLISM, DIET, AND DISEASE LA English DT Article; Book Chapter ID CLINICAL-PRACTICE GUIDELINES; CARDIOVASCULAR-DISEASE RISK; RANDOMIZED CONTROLLED-TRIAL; IMPAIRED GLUCOSE-TOLERANCE; AMERICAN-HEART-ASSOCIATION; CORONARY-ARTERY-DISEASE; LIFE-STYLE INTERVENTION; BODY-MASS INDEX; BLOOD-PRESSURE; MICROVASCULAR COMPLICATIONS C1 [Mechanick, Jeffrey I.] Mt Sinai Sch Med, Div Endocrinol Diabet & Bone Dis, New York, NY 10029 USA. [Marchetti, Albert E.] Univ Med & Dent New Jersey, Dept Prevent Med & Community Hlth, Newark, NJ 07103 USA. [Apovian, Caroline] Boston Univ, Sch Med, Nutr & Weight Management Ctr, Boston, MA 02118 USA. [Benchimol, Alexander Koglin] State Inst Diabet & Endocrinol Rio de Janeiro, Obes & Eating Disorders Grp, Rio De Janeiro, Brazil. [Bisschop, Peter H.] Univ Amsterdam, Acad Med Ctr, Div Endocrinol & Metab, NL-1105 AZ Amsterdam, Netherlands. [Bolio-Galvis, Alexis] Hosp Angeles Pedregal, Dept Gen & Bariatr Surg & Clin Nutr, Mexico City, DF, Mexico. [Bolio-Galvis, Alexis] La Salle Univ, Fac Mexicana Med, Clin Nutr & Gen Surg, Mexico City, DF, Mexico. [Hegazi, Refaat A.] Abbott Nutr, Res & Dev, Columbus, OH USA. [Jenkins, David] Univ Toronto, Dept Nutr Sci, Toronto, ON, Canada. [Mendoza, Enrique] Univ Panama, Sch Med, Panama City, Panama. [Leon Sanz, Miguel] Univ Complutense, Dept Med, Univ Hosp Doce Octubre, Serv Endocrinol & Nutr, E-28040 Madrid, Spain. [Sheu, Wayne Huey-Herng] Taichung Vet Gen Hosp, Div Endocrinol & Metab, Taichung, Taiwan. [Sheu, Wayne Huey-Herng] Chung Shan Med Univ, Coll Med, Taichung, Taiwan. [Sheu, Wayne Huey-Herng] Natl Yang Ming Med Univ, Sch Med, Taipei, Taiwan. [Tatti, Patrizio] ASL RMH, Dept Endocrinol & Diabetol, Rome, Italy. [Tsang, Man-Wo] Hosp Author, United Christian Hosp, Dept Med & Geriatr, Div Diabet & Endocrinol, Hong Kong, Hong Kong, Peoples R China. [Hamdy, Osama] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. RP Mechanick, JI (reprint author), Mt Sinai Sch Med, Div Endocrinol Diabet & Bone Dis, New York, NY 10029 USA. NR 115 TC 0 Z9 0 U1 0 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 978-1-4822-3908-9 PY 2014 BP 209 EP 239 PG 31 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BD1AE UT WOS:000357880800013 ER PT S AU Hu, CH Hua, X Thompson, PM El Fakhri, G Li, QZ AF Hu, Chenhui Hua, Xue Thompson, Paul M. El Fakhri, Georges Li, Quanzheng BE Wu, G Zhang, D Zhou, L TI Inferring Sources of Dementia Progression with Network Diffusion Model SO MACHINE LEARNING IN MEDICAL IMAGING (MLMI 2014) SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 5th International Workshop on Machine Learning in Medical Imaging (MLMI) CY SEP 14, 2014 CL Massachusetts Inst Technol, Cambridge, MA HO Massachusetts Inst Technol DE Sources of dementia; network diffusion; brain morphology; longitudinal study; MRI; Alzheimer's disease ID ALZHEIMERS-DISEASE; DYNAMICS; HEALTH AB Pinpointing the sources of dementia is crucial to the effective treatment of neurodegenerative diseases. In this paper, we model the dementia progression by a diffusive model over the brain network with sparse impulsive stimulations. By solving inverse problems, we localize the possible origins of Alzheimer's disease based on a large set of repeated magnetic resonance imaging (MRI) scans in ADNI. The distribution of the sources averaged over the sample population is evaluated. We find that the dementia sources have different concentrations in the brain lobes for Alzheimer's disease (AD) patients and mild cognitive impairment (MCI) subjects, indicating possible switch of the dementia driving mechanism. Our model provides a quantitative way to perform explanatory analysis of the dynamics of dementia. C1 [Hu, Chenhui; El Fakhri, Georges; Li, Quanzheng] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. [Hu, Chenhui] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Hua, Xue] USC, Keck Sch Med, Los Angeles, CA USA. [Thompson, Paul M.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. RP Hu, CH (reprint author), Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. NR 12 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-10581-9; 978-3-319-10580-2 J9 LECT NOTES COMPUT SC PY 2014 VL 8679 BP 42 EP 49 PG 8 WC Computer Science, Artificial Intelligence; Medical Informatics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BD3US UT WOS:000360206000006 ER PT B AU Anderson, DJ Martin, BM Kirk, AD Sachs, DH AF Anderson, Douglas J. Martin, Benjamin M. Kirk, Allan D. Sachs, David H. BE Kirk, AD Knechtle, SJ Larsen, CP Madsen, JC Pearson, TC Webber, SA TI Large Animal Models of Transplantation SO TEXTBOOK OF ORGAN TRANSPLANTATION LA English DT Article; Book Chapter ID RENAL-ALLOGRAFT SURVIVAL; MAJOR HISTOCOMPATIBILITY COMPLEX; HEMATOPOIETIC-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; NONHUMAN PRIMATE MODEL; DONOR-SPECIFIC TRANSFUSION; LONG-TERM TOLERANCE; ANTI-CD40 MONOCLONAL-ANTIBODY; PRECLINICAL CANINE MODEL; THORACIC-DUCT DRAINAGE C1 [Anderson, Douglas J.; Martin, Benjamin M.] Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. [Kirk, Allan D.] Duke Univ, Med Ctr, Duke Univ Hlth Syst, Durham, NC USA. [Sachs, David H.] Harvard Univ, Sch Med, Surg, Boston, MA USA. [Sachs, David H.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Anderson, DJ (reprint author), Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. NR 361 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 978-1-118-88962-6; 978-1-118-87014-3 PY 2014 BP 185 EP 207 D2 10.1002/9781118873434 PG 23 WC Transplantation SC Transplantation GA BC7MX UT WOS:000355005300016 ER PT B AU Craig, JM Lee, S Vlahakes, GJ Madsen, JC AF Craig, John M. Lee, Soyoung Vlahakes, Gus J. Madsen, Joren C. BE Kirk, AD Knechtle, SJ Larsen, CP Madsen, JC Pearson, TC Webber, SA TI Heart Transplantation Procedure and Surgical Technique SO TEXTBOOK OF ORGAN TRANSPLANTATION LA English DT Article; Book Chapter ID HEPARIN-INDUCED THROMBOCYTOPENIA; DONOR MITRAL-VALVE; CARDIAC TRANSPLANTATION; LUNG-TRANSPLANTATION; TRICUSPID ANNULOPLASTY; INTERNATIONAL-SOCIETY; BICAVAL TECHNIQUE; BENCH REPAIR; EXPERIENCE; DISEASE C1 [Craig, John M.] Baptist Mem Hosp, Div Cardiac Surg, Memphis, TN 38146 USA. [Lee, Soyoung; Vlahakes, Gus J.; Madsen, Joren C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Lee, Soyoung; Vlahakes, Gus J.; Madsen, Joren C.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. RP Craig, JM (reprint author), Baptist Mem Hosp, Div Cardiac Surg, Memphis, TN 38146 USA. NR 61 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 978-1-118-88962-6; 978-1-118-87014-3 PY 2014 BP 657 EP 666 D2 10.1002/9781118873434 PG 10 WC Transplantation SC Transplantation GA BC7MX UT WOS:000355005300059 ER PT B AU Shah, KB Madsen, JC Mehra, MR AF Shah, Keyur B. Madsen, Joren C. Mehra, Mandeep R. BE Kirk, AD Knechtle, SJ Larsen, CP Madsen, JC Pearson, TC Webber, SA TI Clinical Allograft Rejection Syndromes in Heart Transplantation SO TEXTBOOK OF ORGAN TRANSPLANTATION LA English DT Article; Book Chapter ID CORONARY-ARTERY-DISEASE; ANTIBODY-MEDIATED REJECTION; CARDIAC MAGNETIC-RESONANCE; LEFT-VENTRICULAR FUNCTION; TOTAL LYMPHOID IRRADIATION; BRAIN NATRIURETIC PEPTIDE; GENE-EXPRESSION; DOPPLER-ECHOCARDIOGRAPHY; ENDOMYOCARDIAL BIOPSY; HUMORAL REJECTION C1 [Shah, Keyur B.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Shah, Keyur B.] Med Coll Virginia Hosp, Richmond, VA USA. [Madsen, Joren C.] Massachusetts Gen Hosp, Surg, Boston, MA 02114 USA. [Madsen, Joren C.] Massachusetts Gen Hosp, Cardiac Surg, Boston, MA 02114 USA. [Mehra, Mandeep R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Shah, KB (reprint author), Virginia Commonwealth Univ, Richmond, VA 23284 USA. NR 131 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 978-1-118-88962-6; 978-1-118-87014-3 PY 2014 BP 802 EP 812 D2 10.1002/9781118873434 PG 11 WC Transplantation SC Transplantation GA BC7MX UT WOS:000355005300072 ER PT B AU Vagefi, PA Stock, PG AF Vagefi, Parsia A. Stock, Peter G. BE Kirk, AD Knechtle, SJ Larsen, CP Madsen, JC Pearson, TC Webber, SA TI Clinical Allograft Rejection Syndromes in Pancreas and Islet Transplantation SO TEXTBOOK OF ORGAN TRANSPLANTATION LA English DT Article; Book Chapter ID ANTIBODY-MEDIATED REJECTION; PERCUTANEOUS BIOPSY; EXPERIENCE; RECIPIENTS; KIDNEY; GRAFT; SCHEMA C1 [Vagefi, Parsia A.] Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA 02114 USA. [Vagefi, Parsia A.] Harvard Univ, Sch Med, Boston, MA USA. [Stock, Peter G.] Univ Calif San Francisco, Div Transplant Surg, San Francisco, CA 94143 USA. RP Vagefi, PA (reprint author), Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA 02114 USA. NR 32 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 978-1-118-88962-6; 978-1-118-87014-3 PY 2014 BP 824 EP 829 D2 10.1002/9781118873434 PG 6 WC Transplantation SC Transplantation GA BC7MX UT WOS:000355005300074 ER PT B AU Kawai, T Sachs, DH Cosimi, AB AF Kawai, Tatsuo Sachs, David H. Cosimi, A. Benedict BE Kirk, AD Knechtle, SJ Larsen, CP Madsen, JC Pearson, TC Webber, SA TI Clinical Transplantation Tolerance SO TEXTBOOK OF ORGAN TRANSPLANTATION LA English DT Article; Book Chapter ID RENAL-ALLOGRAFT REJECTION; TOTAL-LYMPHOID IRRADIATION; DONOR LIVER-TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; MIXED LYMPHOHEMATOPOIETIC CHIMERISM; NONLETHAL PREPARATIVE REGIMEN; OPERATIONAL IMMUNE TOLERANCE; BLOOD MONONUCLEAR-CELLS; REGULATORY T-CELLS; KIDNEY-TRANSPLANTATION C1 [Kawai, Tatsuo; Sachs, David H.; Cosimi, A. Benedict] Harvard Univ, Sch Med, Surg, Boston, MA 02134 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Kawai, T (reprint author), Harvard Univ, Sch Med, Surg, Boston, MA 02134 USA. NR 167 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, W SUSSEX PO 19 8SQ, ENGLAND BN 978-1-118-88962-6; 978-1-118-87014-3 PY 2014 BP 844 EP 854 D2 10.1002/9781118873434 PG 11 WC Transplantation SC Transplantation GA BC7MX UT WOS:000355005300077 ER PT B AU Astor, TL AF Astor, Todd L. BE Kirk, AD Knechtle, SJ Larsen, CP Madsen, JC Pearson, TC Webber, SA TI Recurrent Disease after Lung Transplantation SO TEXTBOOK OF ORGAN TRANSPLANTATION LA English DT Article; Book Chapter ID PULMONARY ALVEOLAR PROTEINOSIS; LANGERHANS-CELL HISTIOCYTOSIS; ADVANCED BRONCHIOLOALVEOLAR CARCINOMA; DESQUAMATIVE INTERSTITIAL PNEUMONIA; TUBEROUS SCLEROSIS COMPLEX; COLONY-STIMULATING FACTOR; AIR-FLOW LIMITATION; HIGH-RESOLUTION CT; CAPILLARY HEMANGIOMATOSIS; ALPHA(1)-ANTITRYPSIN DEFICIENCY C1 [Astor, Todd L.] Harvard Univ, Sch Med, Med, Boston, MA 02115 USA. [Astor, Todd L.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Lung & Heart Lung Transplant Program, Boston, MA 02114 USA. RP Astor, TL (reprint author), Harvard Univ, Sch Med, Med, Boston, MA 02115 USA. NR 165 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 978-1-118-88962-6; 978-1-118-87014-3 PY 2014 BP 898 EP 909 D2 10.1002/9781118873434 PG 12 WC Transplantation SC Transplantation GA BC7MX UT WOS:000355005300081 ER PT B AU Fishman, JA Avery, RK AF Fishman, Jay A. Avery, Robin K. BE Kirk, AD Knechtle, SJ Larsen, CP Madsen, JC Pearson, TC Webber, SA TI Late Infectious Disease after Organ Transplantation SO TEXTBOOK OF ORGAN TRANSPLANTATION LA English DT Article; Book Chapter ID EPSTEIN-BARR-VIRUS; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER; POLYOMAVIRUS-ASSOCIATED NEPHROPATHY; GANCICLOVIR-RESISTANT CYTOMEGALOVIRUS; ASPERGILLUS-GALACTOMANNAN ANTIGEN; VIRAL LOAD ASSAYS; OF-THE-LITERATURE; T-CELL IMMUNITY; BK VIRUS; RENAL-TRANSPLANTATION C1 [Fishman, Jay A.] Massachusetts Gen Hosp, MGH Transplantat Ctr, Boston, MA 02114 USA. [Fishman, Jay A.] Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, Boston, MA 02114 USA. [Fishman, Jay A.] Harvard Univ, Sch Med, Med, Boston, MA USA. [Avery, Robin K.] Johns Hopkins Univ, Sch Med, Div Infect Dis Transplant Oncol, Baltimore, MD USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, MGH Transplantat Ctr, Boston, MA 02114 USA. NR 155 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 978-1-118-88962-6; 978-1-118-87014-3 PY 2014 BP 1117 EP 1133 D2 10.1002/9781118873434 PG 17 WC Transplantation SC Transplantation GA BC7MX UT WOS:000355005300095 ER PT B AU Yeh, H Martins, P Markmann, JF AF Yeh, Heidi Martins, Paulo Markmann, James F. BE Kirk, AD Knechtle, SJ Larsen, CP Madsen, JC Pearson, TC Webber, SA TI Long-term Outcomes after Liver Transplantation SO TEXTBOOK OF ORGAN TRANSPLANTATION LA English DT Article; Book Chapter ID SINGLE-CENTER EXPERIENCE; ADULT LIVING DONOR; HEPATITIS-C VIRUS; ANTIBODY-POSITIVE DONORS; CARDIAC DEATH DONORS; ONSET DIABETES-MELLITUS; BLOOD-GROUP BARRIERS; BODY-MASS INDEX; UNITED-STATES; RISK-FACTORS C1 [Yeh, Heidi] Harvard Univ, Sch Med, Pediat Transplantat, Boston, MA 02115 USA. [Martins, Paulo] Harvard Univ, Sch Med, Boston, MA USA. [Markmann, James F.] Harvard Univ, Sch Med, Surg, Boston, MA USA. [Yeh, Heidi] Massachusetts Gen Hosp, Surg, Boston, MA 02114 USA. [Martins, Paulo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Markmann, James F.] Massachusetts Gen Hosp, Div Transplantat, Boston, MA 02114 USA. RP Yeh, H (reprint author), Harvard Univ, Sch Med, Pediat Transplantat, Boston, MA 02115 USA. NR 189 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 978-1-118-88962-6; 978-1-118-87014-3 PY 2014 BP 1267 EP 1279 D2 10.1002/9781118873434 PG 13 WC Transplantation SC Transplantation GA BC7MX UT WOS:000355005300105 ER PT B AU Formica, RN Delmonico, FL AF Formica, Richard N., Jr. Delmonico, Francis L. BE Kirk, AD Knechtle, SJ Larsen, CP Madsen, JC Pearson, TC Webber, SA TI Transplant Ethics for Clinicians SO TEXTBOOK OF ORGAN TRANSPLANTATION LA English DT Article; Book Chapter ID LIVE-ORGAN DONOR; KIDNEY; GUIDELINES C1 [Formica, Richard N., Jr.] Yale Univ, Sch Med, Med & Surg, New Haven, CT 06520 USA. [Formica, Richard N., Jr.] Yale Univ, Sch Med, Transplant Nephrol, New Haven, CT USA. [Formica, Richard N., Jr.] Yale Univ, Sch Med, Adult & Pediat Kidney Transplantat, New Haven, CT USA. [Formica, Richard N., Jr.] Yale Univ, Sch Med, Pancreas Transplantat, New Haven, CT USA. [Delmonico, Francis L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg,Transplant Ctr, Boston, MA USA. [Delmonico, Francis L.] New England Organ Bank Inc, Waltham, MA USA. RP Formica, RN (reprint author), Yale Univ, Sch Med, Med & Surg, New Haven, CT 06520 USA. NR 10 TC 0 Z9 0 U1 1 U2 2 PU JOHN WILEY & SONS PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, W SUSSEX PO 19 8SQ, ENGLAND BN 978-1-118-88962-6; 978-1-118-87014-3 PY 2014 BP 1641 EP 1644 D2 10.1002/9781118873434 PG 4 WC Transplantation SC Transplantation GA BC7MX UT WOS:000355005300137 ER PT S AU Oaklander, AL AF Oaklander, Anne Louise BE Carstens, E Akiyama, T TI Neuropathic Itch SO ITCH: MECHANISMS AND TREATMENT SE Frontiers in Neuroscience-Series LA English DT Article; Book Chapter ID TRIGEMINAL TROPHIC SYNDROME; TOXIN TYPE-A; UNILATERAL NEUROGENIC PRURITUS; CAPSAICIN-SENSITIVE AFFERENTS; POSITRON-EMISSION-TOMOGRAPHY; SPINOTHALAMIC TRACT NEURONS; CREUTZFELDT-JAKOB-DISEASE; HISTAMINE-INDUCED ITCH; POSSIBLE ANIMAL-MODEL; DORSAL-HORN NEURONS C1 [Oaklander, Anne Louise] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Oaklander, Anne Louise] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol Neuropathol, Boston, MA 02115 USA. RP Oaklander, AL (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 164 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 SN 2154-5723 BN 978-1-4665-0544-5 J9 FRONT NEUROSCI JI Front. Neurosci. PY 2014 BP 89 EP 118 D2 10.1201/b16573 PG 30 WC Neurosciences SC Neurosciences & Neurology GA BD3OA UT WOS:000359978000009 ER PT S AU Ma, QF AF Ma, Qiufu BE Carstens, E Akiyama, T TI Itch Modulation by VGLUT2-Dependent Glutamate Release from Somatic Sensory Neurons SO ITCH: MECHANISMS AND TREATMENT SE Frontiers in Neuroscience-Series LA English DT Article; Book Chapter ID DORSAL-ROOT GANGLIA; INORGANIC-PHOSPHATE COTRANSPORTER; RAT SPINAL-CORD; STATE-DEPENDENT INHIBITION; PRIMARY AFFERENT TERMINALS; VESICULAR GLUTAMATE; MOLECULAR-MECHANISMS; BEHAVIORAL-RESPONSES; SCRATCHING BEHAVIOR; EXCITATORY NEURONS C1 [Ma, Qiufu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ma, Qiufu] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Ma, QF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 92 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 SN 2154-5723 BN 978-1-4665-0544-5 J9 FRONT NEUROSCI JI Front. Neurosci. PY 2014 BP 359 EP 372 D2 10.1201/b16573 PG 14 WC Neurosciences SC Neurosciences & Neurology GA BD3OA UT WOS:000359978000023 ER PT B AU Fisher, MB Soegaard, N Steinberg, DR Mauck, RL AF Fisher, Matthew B. Soeegaard, Nicole Steinberg, David R. Mauck, Robert L. GP ASME TI TRAJECTORY-BASED TISSUE ENGINEERING FOR CARTILAGE REPAIR: CORRELATION BETWEEN MATURATION RATE AND INTEGRATION CAPACITY 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 [Fisher, Matthew B.; Soeegaard, Nicole; Steinberg, David R.; Mauck, Robert L.] Univ Penn, McKay Orthopaed Res Lab, Philadelphia, PA 19104 USA. [Fisher, Matthew B.; Steinberg, David R.; Mauck, Robert L.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Fisher, MB (reprint author), Univ Penn, McKay Orthopaed Res Lab, Philadelphia, PA 19104 USA. RI Fisher, Matthew/M-5809-2016 OI Fisher, Matthew/0000-0002-3212-0870 NR 9 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 V01AT17A022 PG 2 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA BD2YH UT WOS:000359389200225 ER PT B AU Retarekar, R Ramachandran, M Dickerhoff, B Harbaugh, R Hasan, D Ogilvy, C Rosenwasser, R Raghavan, ML AF Retarekar, R. Ramachandran, M. Dickerhoff, B. Harbaugh, R. Hasan, D. Ogilvy, C. Rosenwasser, R. Raghavan, M. L. GP ASME TI HEMODYNAMICS AND NATURAL HISTORY OUTCOME IN UNRUPTURED INTRACRANIAL ANEURYSMS: A PROSPECTIVE LONGITUDINAL COHORT STUDY 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 [Retarekar, R.; Ramachandran, M.; Dickerhoff, B.; Raghavan, M. L.] Univ Iowa, Dept Biomed Engn, Iowa City, IA 52242 USA. [Harbaugh, R.] Penn State Hershey Med Ctr, Dept Neurosurg, Hershey, PA USA. [Hasan, D.] Univ Iowa Hosp & Clin, Dept Neurosurg, Iowa City, IA 52242 USA. [Ogilvy, C.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Rosenwasser, R.] Thomas Jefferson Univ Hosp, Dept Neurosurg, Philadelphia, PA 19107 USA. RP Retarekar, R (reprint author), Univ Iowa, Dept Biomed Engn, Iowa City, IA 52242 USA. NR 6 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 V01AT18A004 PG 2 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA BD2YH UT WOS:000359389200236 ER PT B AU Zeinali-Davarani, S Chow, MJ Turcotte, R Zhang, KY AF Zeinali-Davarani, Shahrokh Chow, Ming-Jay Turcotte, Raphael Zhang, Katherine Yanhang GP ASME TI CONSTITUTIVE MODELING OF BIAXIAL MECHANICAL RESPONSE OF ARTERIES SUBJECTED TO GRADUAL ELASTIN DEGRADATION 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 [Zeinali-Davarani, Shahrokh; Chow, Ming-Jay; Turcotte, Raphael] Boston Univ, Dept Mech Engn, Boston, MA 02215 USA. [Turcotte, Raphael; Zhang, Katherine Yanhang] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Zhang, Katherine Yanhang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Adv Microscopy Program,Ctr Syst Biol, Boston, MA 02114 USA. [Zhang, Katherine Yanhang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Zeinali-Davarani, S (reprint author), Boston Univ, Dept Mech Engn, Boston, MA 02215 USA. NR 5 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 V01AT13A010 PG 2 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA BD2YH UT WOS:000359389200166 ER PT B AU Chow, MJ Turcotte, R Zhang, KY AF Chow, Ming-Jay Turcotte, Raphael Zhang, Katherine Yanhang GP ASME TI ELASTIN IN THE ARTERIAL ECM: INTERACTIONS WITH COLLAGEN AND THE MECHANICAL PROPERTIES AFTER ELASTIN DEGRADATION 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 C1 [Chow, Ming-Jay; Zhang, Katherine Yanhang] Boston Univ, Dept Mech Engn, Boston, MA 02215 USA. [Turcotte, Raphael; Zhang, Katherine Yanhang] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Turcotte, Raphael] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Adv Microscopy Program,Ctr Syst Biol, Boston, MA 02114 USA. [Turcotte, Raphael] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Chow, MJ (reprint author), Boston Univ, Dept Mech Engn, Boston, MA 02215 USA. NR 9 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 V01BT65A002 PG 2 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA BD2YI UT WOS:000359389300296 ER PT B AU Fisher, MB Soegaard, N Esterhai, JL Mauck, RL AF Fisher, Matthew B. Soeegaard, Nicole Esterhai, John L. Mauck, Robert L. GP ASME TI ENGINEERING MENISCUS FORM AND FUNCTION VIA MULTI-LAYER CELL-SEEDED NANOFIBROUS SCAFFOLDS WITH CIRCUMFERENTIALLY ALIGNED FIBERS 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 C1 [Fisher, Matthew B.; Soeegaard, Nicole; Esterhai, John L.; Mauck, Robert L.] Univ Penn, McKay Orthopaed Res Lab, Philadelphia, PA 19104 USA. [Fisher, Matthew B.; Esterhai, John L.; Mauck, Robert L.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Fisher, MB (reprint author), Univ Penn, McKay Orthopaed Res Lab, Philadelphia, PA 19104 USA. RI Fisher, Matthew/M-5809-2016 OI Fisher, Matthew/0000-0002-3212-0870 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 978-0-7918-5561-4 PY 2014 AR V01BT39A012 PG 2 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA BD2YI UT WOS:000359389300107 ER PT J AU Brock, A Krause, S Li, H Kowalski, M Goldberg, MS Collins, JJ Ingber, DE AF Brock, Amy Krause, Silva Li, Hu Kowalski, Marek Goldberg, Michael S. Collins, James J. Ingber, Donald E. TI Silencing HoxA1 by Intraductal Injection of siRNA Lipidoid Nanoparticles Prevents Mammary Tumor Progression in Mice SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID TRANSGENIC MOUSE MODEL; CARCINOMA IN-SITU; TERM-FOLLOW-UP; BREAST-CANCER CELLS; LONG-TERM; GENE-EXPRESSION; DELIVERY; NETWORK; GLAND; INTERFERENCE AB With advances in screening, the incidence of detection of premalignant breast lesions has increased in recent decades; however, treatment options remain limited to surveillance or surgical removal by lumpectomy or mastectomy. We hypothesized that disease progression could be blocked by RNA interference (RNAi) therapy and set out to develop a targeted therapeutic delivery strategy. Using computational gene network modeling, we identified HoxA1 as a putative driver of early mammary cancer progression in transgenic C3(1)-SV40TAg mice. Silencing this gene in cultured mouse or human mammary tumor spheroids resulted in increased acinar lumen formation, reduced tumor cell proliferation, and restoration of normal epithelial polarization. When the HoxA1 gene was silenced in vivo via intraductal delivery of nanoparticle-formulated small interfering RNA (siRNA) through the nipple of transgenic mice with early-stage disease, mammary epithelial cell proliferation rates were suppressed, loss of estrogen and progesterone receptor expression was prevented, and tumor incidence was reduced by 75%. This approach that leverages new advances in systems biology and nanotechnology offers a novel noninvasive strategy to block breast cancer progression through targeted silencing of critical genes directly within the mammary epithelium. C1 [Brock, Amy; Li, Hu; Kowalski, Marek; Collins, James J.; Ingber, Donald E.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Krause, Silva; Ingber, Donald E.] Harvard Univ, Sch Med, Boston Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. [Krause, Silva; Ingber, Donald E.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Goldberg, Michael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Collins, James J.] Boston Univ, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Ingber, DE (reprint author), Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. EM don.ingber@wyss.harvard.edu FU Department of Defense Breast Cancer Innovator Award [W81XWH-08-1-0659]; Wyss Institute for Biologically Inspired Engineering at Harvard University; Howard Hughes Medical Institute; SysCODE (Systems-based Consortium for Organ Design Engineering); NIH [RL1DE019021]; Mayo Clinic Center for Individualized Medicine; Mental Retardation and Developmental Disabilities Research Center Molecular Genetics Core Facility at Children's Hospital Boston [NIH-P30-HD18655]; Susan G. Komen Foundation [KG101329] FX This study was funded by the Department of Defense Breast Cancer Innovator Award W81XWH-08-1-0659 (to D.E.I.) and the Wyss Institute for Biologically Inspired Engineering at Harvard University. J.J.C. and H.L. were supported by the Howard Hughes Medical Institute, SysCODE (Systems-based Consortium for Organ Design & Engineering), and NIH grant RL1DE019021. The postdoctoral training of S.K. was supported by the Susan G. Komen Foundation (KG101329). H.L. is supported by the Mayo Clinic Center for Individualized Medicine. Microarray analysis was performed at the Mental Retardation and Developmental Disabilities Research Center Molecular Genetics Core Facility at Children's Hospital Boston (NIH-P30-HD18655) and has been deposited with the NCBI GEO (http://www.ncbi.nlm.nih.gov/geo/) under accession number GSE50813. NR 48 TC 19 Z9 19 U1 4 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JAN 1 PY 2014 VL 6 IS 217 AR 217ra2 PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 282JG UT WOS:000329166500004 PM 24382894 ER PT B AU Ekstein, D Schachter, SC AF Ekstein, Dana Schachter, Steven C. BE Miller, JW Goodkin, HP TI Ketogenic Diet and Alternative Therapies SO EPILEPSY SE Neurology in Practice LA English DT Article; Book Chapter ID EPILEPSY; MANAGEMENT; CHILDREN C1 [Ekstein, Dana] Hadassah Hebrew Univ Med Ctr, Epilepsy Ctr, Dept Neurol, Jerusalem, Israel. [Schachter, Steven C.] Massachusetts Gen Hosp, Dept Neurol, Beth Israel Deaconess Med Ctr, Ctr Integrat Med & Innovat Technol, Boston, MA 02114 USA. [Schachter, Steven C.] Harvard Univ, Sch Med, Boston, MA USA. RP Ekstein, D (reprint author), Hadassah Hebrew Univ Med Ctr, Epilepsy Ctr, Dept Neurol, Jerusalem, Israel. OI Miller, Dana/0000-0002-1752-3137 NR 13 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 978-1-118-45695-8; 978-1-118-45694-1 J9 NEUROL PRACT PY 2014 BP 210 EP 214 D2 10.1002/9781118456989 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA BC9NF UT WOS:000356629200031 ER PT S AU Cottini, F Guidetti, A Prada, CP Hideshima, T Maglio, M Varga, C Chauhan, D Laubach, J Anderson, KC Richardson, PG AF Cottini, Francesca Guidetti, Anna Prada, Claudia Paba Hideshima, Teru Maglio, Michelle Varga, Cindy Chauhan, Dharminder Laubach, Jacob Anderson, Kenneth C. Richardson, Paul G. BE Dou, QP TI Resistance to Proteasome Inhibitors in Multiple Myeloma SO RESISTANCE TO PROTEASOME INHIBITORS IN CANCER: MOLECULAR MECHANISMS AND STRATEGIES TO OVERCOME RESISTANCE SE Resistance to Targeted Anti-Cancer Therapeutics LA English DT Article; Book Chapter DE Proteasome inhibitor; Carfilzomib; Bortezomib; Drug resistance; Multiple myeloma ID INTRACELLULAR PROTEIN-DEGRADATION; BORTEZOMIB PLUS MELPHALAN; ACID-BASED PROTEASOME; KAPPA-B ACTIVATION; ANTITUMOR-ACTIVITY; 20S PROTEASOME; COMBINATION TREATMENT; REFRACTORY MYELOMA; PS-341 RESISTANCE; BACTERIAL-CELLS AB Multiple myeloma (MM) is a clonal proliferation of malignant plasma cells in the bone marrow associated with a spectrum of clinical symptoms including bone destruction, anemia, hypercalcemia, and renal failure. Although MM remains incurable, a dramatic paradigm shift in the treatment of MM has occurred over the past decade through the introduction of novel agents, including the development of small molecule inhibitors targeting the proteasome. Among the proteasome inhibitors (PIs), bortezomib (BTZ) and carfilzomib (CFZ) have been approved by the FDA for treatment of relapsed/refractory MM in 2003 and 2012, respectively. Recently, other PIs, such as ixazomib (MLN-9708), oprozomib (ONX0912), and marizomib (NPI-0052), have been under evaluation in preclinical and clinical studies. Indeed, it is now well known that malignant plasma cells are exquisitely sensitive to proteasome inhibitors due to protein overload and ER stress. Unfortunately, relapse of myeloma develops due to acquisition of resistance to proteasome inhibitors. Specifically, mutations in overexpression of proteins belonging to the proteasome complex, upregulation of transporter channels or cytochrome components, induction of alternative compensative mechanisms such as the aggresome pathway, and modulation of downstream pathways have been all reported as possible mechanisms of proteasome inhibitor resistance. In this chapter, we will first briefly describe the structure and function of the proteasome in normal and malignant plasma cells, and then define the major mechanisms of resistance to proteasome inhibition, and clinical approaches to overcoming these pathways in the context of both clinical application of PIs and rational combinations of them with other agents in the treatment of MM. C1 [Cottini, Francesca; Prada, Claudia Paba; Hideshima, Teru; Maglio, Michelle; Varga, Cindy; Chauhan, Dharminder; Laubach, Jacob; Anderson, Kenneth C.; Richardson, Paul G.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Div Hematol Malignancy, Dept Med Oncol, Boston, MA 02115 USA. [Guidetti, Anna] Univ Milan, Milan, Italy. RP Richardson, PG (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Div Hematol Malignancy, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM francesca_cottini@dfci.harvard.edu; anna.guidetti@istitutotumori.mi.it; claudiap_prada@dfci.harvard.edu; teru_hideshima@dfci.harvard.edu; michelle_maglio@dfci.harvard.edu; cindy_varga@dfci.harvard.edu; dharminder_chauhan@dfci.harvard.edu; jacobp_laubach@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu; paul_richardson@dfci.harvard.edu NR 99 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 2196-5501 BN 978-3-319-06752-0; 978-3-319-06751-3 J9 RESIST TARGET ANTI-C PY 2014 VL 3 BP 47 EP 80 DI 10.1007/978-3-319-06752-0_2 D2 10.1007/978-3-319-06752-0 PG 34 WC Biochemistry & Molecular Biology; Oncology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Oncology; Pharmacology & Pharmacy GA BD2LI UT WOS:000358864400002 ER PT J AU Clark, TK Newman, MC Merfeld, DM Young, LR AF Clark, Torin K. Newman, Michael C. Merfeld, Daniel M. Young, Laurence R. GP IEEE TI Pilot Control and Stabilization of a Rate-Controlled Vehicle in Hyper-Gravity SO 2014 IEEE AEROSPACE CONFERENCE LA English DT Proceedings Paper CT IEEE Aerospace Conference CY MAR 01-08, 2014 CL Big Sky, MT SP IEEE ID CANADIAN VESTIBULAR EXPERIMENTS; SPACE MOTION SICKNESS; GRAVITOINERTIAL FORCE; SPATIAL ORIENTATION; ARTIFICIAL GRAVITY; HEAD MOVEMENTS; WEIGHTLESSNESS; ADAPTATION; SPACEFLIGHT; MISSION AB Astronauts experience multiple altered gravity environments during space missions, in which they need to maintain sufficient performance for vehicle control tasks such as planetary landing and vehicle docking. We aimed to use hyper-gravity as an altered gravity test-bed to study pilot manual control performance. A long-radius (7.6 m) centrifuge (NASTAR Center's ATFS-400) was utilized to produce hyper-gravity. Subjects (N=12) were tasked with trying to "keep the cab as upright as possible" using a rotational hand controller in response to a pseudo-random roll disturbance in the dark. The control law was "rate-control" such that stick deflection was proportional to commanded roll rate, similar to a lunar landing vehicle. During initial exposure to hyper-gravity, pilot performance showed significant degradations relative to the 1 G performance baseline, in terms of increases in the root mean square (RMS) error in roll tilt. On average in hyper-gravity, RMS scores increased by 25% over 1 G levels. Subjects also reported increases in workload in hyper-gravity. Performance significantly improved in hyper-gravity over time. After several minutes the performance in hyper-gravity returned to near the 1 G baseline performance level. This is likely to be a critical time period for planetary landings with fuel constrained vehicles. These control impairments may impact not only flight performance, but also vehicle and crew safety. C1 [Clark, Torin K.; Young, Laurence R.] MIT, Cambridge, MA 02139 USA. [Newman, Michael C.] NASTAR Ctr, Southampton, PA 18966 USA. [Merfeld, Daniel M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Clark, TK (reprint author), MIT, 77 Massachusetts Ave 37-219, Cambridge, MA 02139 USA. EM torin@mit.edu; mnewman@nastarcenter.com; daniel_merfeld@meei.harvard.edu; lry@mit.edu NR 30 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-1622-1 PY 2014 PG 8 WC Engineering, Aerospace; Engineering, Electrical & Electronic SC Engineering GA BC8RQ UT WOS:000356039101074 ER PT J AU Clark, T AF Clark, Tim TI Next Generation Scientific Publishing and the Web of Data SO SEMANTIC WEB LA English DT Editorial Material DE Scientific publishing; biomedical communications; semantic web; argumentation; reproducibility; data integrity; ontologies; scientific data; reusibility ID CITATION; CELLS AB Next Generation scientific publishing will exploit both the web of documents and the web of data to help resolve many of today's serious problems in reproducibility, citation and citation-claim integrity, and publication volume intractability. Here we briefly review several developments in this field using new semantic models and approaches to help achieve more robust scientific, and particularly biomedical, communications. C1 [Clark, Tim] Harvard Univ, Sch Med, Boston, MA 02138 USA. [Clark, Tim] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Clark, Tim] Univ Manchester, Sch Comp Sci, Manchester, Lancs, England. RP Clark, T (reprint author), Harvard Univ, Sch Med, Boston, MA 02138 USA. NR 27 TC 1 Z9 1 U1 1 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1570-0844 EI 2210-4968 J9 SEMANT WEB JI Semant. Web PY 2014 VL 5 IS 4 BP 257 EP 259 DI 10.3233/SW-140139 PG 3 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Theory & Methods SC Computer Science GA CM7KU UT WOS:000357872100001 ER PT J AU Ciccarese, P Shotton, D Peroni, S Clark, T AF Ciccarese, Paolo Shotton, David Peroni, Silvio Clark, Tim TI CiTO plus SWAN: The web semantics of bibliographic records, citations, evidence and discourse relationships SO SEMANTIC WEB LA English DT Article DE Bibliographic ontology; FRBR; scientific discourse; OWL ID MEDICAL SUBJECT-HEADINGS AB Most literature searching in biomedicine is now conducted via PubMed, Google Scholar or other web-based bibliographic search mechanisms. Yet until now a public, open, interoperable and complete web-adapted information schema for bibliographic citations, bibliographic references and scientific discourse has not been available. Such a schema, expressed in the form of a description logic compatible with current web semantics approaches, would provide the ability to treat bibliographic references and citations, and rhetorical discourse in scientific publications, as semantic metadata on the web, with all the benefits that implies for organization, search and mash-up of web-based scientific information. In this paper we present CiTO + SWAN, a set of fully harmonized ontology modules resulting from the harmonization of CiTO (the Citation Typing Ontology) with SWAN (Semantic Web Applications in Neuromedicine), which we have developed by jointly adapting and evolving version 1.6 of CiTO, the Citation Typing Ontology, and version 1.2 of the SWAN Scientific Discourse Ontology (v1.2). The CiTO + SWAN model is specified in OWL 2 DL, is fully modular, and inherently supports agent-based searching and mash-ups. Through the harmonization activity presented here, and previous work that harmonized SWAN with the SIOC (Semantically-Interlinked Online Communities) Ontology for describing blogs, wikis and discussion groups, we have construct the basis of a powerful new web framework for scientific communications. C1 [Ciccarese, Paolo; Clark, Tim] Massachusetts Gen Hosp, Dept Neurol, Mindinformat, Cambridge, MA 02139 USA. [Ciccarese, Paolo; Clark, Tim] Harvard Univ, Sch Med, Boston, MA USA. [Shotton, David; Peroni, Silvio] Univ Oxford, Dept Zool, Image Bioinformat Res Grp, Oxford OX1 3PS, England. [Peroni, Silvio] Univ Bologna, Dept Comp Sci, I-40127 Bologna, BO, Italy. RP Clark, T (reprint author), Massachusetts Gen Hosp, Dept Neurol, Mindinformat, 65 Landsdowne St, Cambridge, MA 02139 USA. EM tim_clark@harvard.edu FU philanthropic foundation; EPSRC grant [EP/E021352/1]; JISC Open Citations Project FX SWAN (PC and TC, Harvard): The development of SWAN was funded by generous grants from a philanthropic foundation that wishes to remain anonymous. We are grateful to Eric Prud'hommeaux of W3C for valuable technical support, and to Anita de Waard of Elsevier for many helpful comments and references and for her enthusiastic support.; CiTO and FaBiO (DS and SP, Oxford): The initial development of CiTO was undertaken as part of the work of the Ontogenesis Network, supported by EPSRC grant EP/E021352/1. The harmonization activity reported here, which paralleled the restructuring of CiTO and the creation of FaBiO, were initially undertaken without specific grant funding, and were then supported by the JISC Open Citations Project. NR 30 TC 2 Z9 2 U1 2 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1570-0844 EI 2210-4968 J9 SEMANT WEB JI Semant. Web PY 2014 VL 5 IS 4 BP 295 EP 311 DI 10.3233/SW-130098 PG 17 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Theory & Methods SC Computer Science GA CM7KU UT WOS:000357872100003 ER PT J AU Ciccarese, P Peroni, S AF Ciccarese, Paolo Peroni, Silvio TI The Collections Ontology: Creating and handling collections in OWL 2 DL frameworks SO SEMANTIC WEB LA English DT Article DE OWL; collection; list; bag; set AB The RDF collections and containers is one of the most used features by RDF technicians and practitioners. Although some work has been published in the past, there is not a standard and accepted way for defining collections within OWL DL frameworks. Here, we attempt to address this issue with the introduction of the Collections Ontology (CO) version 2.0. CO is an OWL 2 DL ontology developed for creating sets, bags and lists of resources, and for inferring collection properties even in the presence of incomplete information. C1 [Ciccarese, Paolo] Massachusetts Gen Hosp, Dept Neurol, Mindinformat, Cambridge, MA 02139 USA. [Ciccarese, Paolo] Harvard Univ, Sch Med, Boston, MA USA. [Peroni, Silvio] Univ Bologna, Dept Comp Sci & Engn, I-40127 Bologna, BO, Italy. RP Ciccarese, P (reprint author), Massachusetts Gen Hosp, Dept Neurol, Mindinformat, 65 Landsdowne St, Cambridge, MA 02139 USA. EM paolo.ciccarese@gmail.com OI Peroni, Silvio/0000-0003-0530-4305 NR 24 TC 3 Z9 3 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1570-0844 EI 2210-4968 J9 SEMANT WEB JI Semant. Web PY 2014 VL 5 IS 6 BP 515 EP 529 DI 10.3233/SW-130121 PG 15 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Theory & Methods SC Computer Science GA CM7KY UT WOS:000357872700006 ER PT B AU Woodruff, SC Arnkoff, DB Glass, CR Hindman, RK AF Woodruff, Scott C. Arnkoff, Diane B. Glass, Carol R. Hindman, Robert K. BE Ie, A Ngnoumen, CT Langer, EJ TI Mindfulness and Anxiety SO WILEY BLACKWELL HANDBOOK OF MINDFULNESS, VOLS I AND II LA English DT Article; Book Chapter ID OBSESSIVE-COMPULSIVE DISORDER; STRESS REDUCTION PROGRAM; QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; 3-YEAR FOLLOW-UP; COGNITIVE THERAPY; COMMITMENT THERAPY; CANCER OUTPATIENTS; BEHAVIOR-THERAPY; PANIC DISORDER C1 [Glass, Carol R.] Catholic Univ Amer, Psychol, Washington, DC 20064 USA. [Glass, Carol R.] Catholic Univ Amer, Undergrad Program, Washington, DC 20064 USA. [Glass, Carol R.] Amer Psychol Assoc, Washington, DC USA. [Glass, Carol R.] Soc Explorat Psychotherapy Integrat, Board Directors, Los Angeles, CA USA. [Hindman, Robert K.] Beck Inst Cognit Behav Therapy, Bala Cynwyd, PA USA. RP Woodruff, SC (reprint author), Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. NR 129 TC 0 Z9 0 U1 1 U2 3 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-29490-1; 978-1-118-29487-1 PY 2014 BP 732 EP 754 D2 10.1002/9781118294895 PG 23 WC Psychology, Clinical SC Psychology GA BC7HY UT WOS:000354891500042 ER PT B AU Fuentes-Orrego, JM Perez-Johnston, R Sahani, DV AF Fuentes-Orrego, Jorge M. Perez-Johnston, Rocio Sahani, Dushyant V. BE Saba, L Suri, JS TI CT of the Aorta and Splanchnic Vessels SO MULTI-DETECTOR CT IMAGING: PRINCIPLES, HEAD, NECK, AND VASCULAR SYSTEMS LA English DT Article; Book Chapter ID SUPERIOR MESENTERIC-ARTERIES; LOW TUBE VOLTAGE; INTRAMURAL HEMATOMA; CONTRAST AGENT; THERAPEUTIC OPTIONS; CLINICAL-FEATURES; IMPENDING RUPTURE; ABDOMINAL-AORTA; DYNAMIC CT; HELICAL CT C1 [Fuentes-Orrego, Jorge M.; Perez-Johnston, Rocio; Sahani, Dushyant V.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Fuentes-Orrego, Jorge M.; Perez-Johnston, Rocio; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Fuentes-Orrego, JM (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 34 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 978-1-4398-9384-5; 978-1-4398-9380-7 PY 2014 BP 423 EP 436 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BC7QY UT WOS:000355149500020 ER PT B AU Azzoli, CG Pisters, KMW AF Azzoli, Christopher G. Pisters, Katherine M. W. BE Roth, JA Hong, WK Komaki, RU Tsao, AS Chang, JY Blackmon, SH TI Neoadjuvant Chemotherapy for Resectable Non-Small Cell Lung Cancer SO LUNG CANCER,4TH EDITION LA English DT Article; Book Chapter ID PHASE-II TRIAL; RANDOMIZED CONTROLLED-TRIAL; VINORELBINE PLUS CISPLATIN; ONCOLOGY-GROUP TRIAL; LONG-TERM SURVIVAL; PREOPERATIVE CHEMOTHERAPY; INDUCTION CHEMOTHERAPY; FOLLOW-UP; CARBOPLATIN-PACLITAXEL; END-POINTS C1 [Azzoli, Christopher G.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Pisters, Katherine M. W.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. RP Azzoli, CG (reprint author), Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 76 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-46876-0; 978-1-118-46874-6 PY 2014 BP 290 EP 308 D2 10.1002/9781118468791 PG 19 WC Oncology; Respiratory System SC Oncology; Respiratory System GA BC7ET UT WOS:000354798900020 ER PT B AU Gainor, JF Shaw, AT AF Gainor, Justin F. Shaw, Alice T. BE Roth, JA Hong, WK Komaki, RU Tsao, AS Chang, JY Blackmon, SH TI Targeting ALK Rearrangements SO LUNG CANCER,4TH EDITION LA English DT Article; Book Chapter ID CELL-LUNG-CANCER; ANAPLASTIC LYMPHOMA KINASE; RECEPTOR TYROSINE KINASE; EML4-ALK FUSION GENE; NON-HODGKINS-LYMPHOMA; WILD-TYPE EGFR; ACTIVATING MUTATIONS; NEVER-SMOKERS; GROWTH-FACTOR; ONCOGENIC MUTATIONS C1 [Gainor, Justin F.; Shaw, Alice T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Gainor, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. NR 111 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-46876-0; 978-1-118-46874-6 PY 2014 BP 541 EP 556 D2 10.1002/9781118468791 PG 16 WC Oncology; Respiratory System SC Oncology; Respiratory System GA BC7ET UT WOS:000354798900036 ER PT B AU Kratz, JR Jablons, DM AF Kratz, Johannes R. Jablons, David M. BE Roth, JA Hong, WK Komaki, RU Tsao, AS Chang, JY Blackmon, SH TI Prognostic and Predictive Biomarker Signatures SO LUNG CANCER,4TH EDITION LA English DT Article; Book Chapter ID CELL-LUNG-CANCER; GENE-EXPRESSION SIGNATURES; SQUAMOUS-CELL; ADJUVANT CHEMOTHERAPY; SURGICAL RESECTION; MULTIGENE ASSAY; STAGING SYSTEM; BREAST-CANCER; HIGH-RISK; SURVIVAL C1 [Kratz, Johannes R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Jablons, David M.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. RP Kratz, JR (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RI Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 NR 53 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-46876-0; 978-1-118-46874-6 PY 2014 BP 564 EP 571 D2 10.1002/9781118468791 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA BC7ET UT WOS:000354798900038 ER PT B AU McDermott, S O'Connor, OJ Shelly, MJ Blake, MA AF McDermott, Shaunagh O'Connor, Owen J. Shelly, Martin J. Blake, Michael A. BE Saba, L Suri, JS TI Adrenal Gland SO MULTI-DETECTOR CT IMAGING: ABDOMEN, PELVIS, AND CAD APPLICATIONS LA English DT Article; Book Chapter ID CONTRAST-ENHANCED CT; MULTIDETECTOR-ROW CT; LIPID-POOR ADENOMAS; CHEMICAL-SHIFT MRI; COMPUTED-TOMOGRAPHY; HISTOGRAM ANALYSIS; ADRENOCORTICAL CARCINOMA; UNENHANCED CT; PATHOLOGICAL CORRELATION; QUANTITATIVE-EVALUATION C1 [McDermott, Shaunagh; O'Connor, Owen J.; Shelly, Martin J.; Blake, Michael A.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP McDermott, S (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. NR 90 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 978-1-4398-9398-2; 978-1-4398-9397-5 PY 2014 BP 105 EP 119 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BC7EJ UT WOS:000354792700007 ER PT B AU Hirshfeld-Becker, DR Micco, JA Wang, CH Henin, A AF Hirshfeld-Becker, Dina R. Micco, Jamie A. Wang, Christine H. Henin, Aude BE Weeks, JW TI Behavioral Inhibition A Discrete Precursor to Social Anxiety Disorder? SO WILEY BLACKWELL HANDBOOK OF SOCIAL ANXIETY DISORDER LA English DT Article; Book Chapter ID PRESCHOOL-AGED CHILDREN; 5-YEAR FOLLOW-UP; PANIC DISORDER; INFANT TEMPERAMENT; EARLY-CHILDHOOD; MIDDLE CHILDHOOD; COMMUNITY SAMPLE; YOUNG-CHILDREN; SELF-REPORT; PSYCHOMETRIC PROPERTIES C1 [Hirshfeld-Becker, Dina R.; Micco, Jamie A.; Wang, Christine H.; Henin, Aude] Massachusetts Gen Hosp, Child Cognit Behav Therapy Program, Boston, MA 02114 USA. RP Hirshfeld-Becker, DR (reprint author), Massachusetts Gen Hosp, Child Cognit Behav Therapy Program, Boston, MA 02114 USA. NR 143 TC 1 Z9 1 U1 1 U2 3 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-65390-6; 978-1-119-96860-3 PY 2014 BP 133 EP 158 D2 10.1002/9781118653920 PG 26 WC Psychology, Clinical SC Psychology GA BC7FR UT WOS:000354811600007 ER PT J AU Kang, JX AF Kang, Jing X. TI Nutritional Problems and Solutions for the Modern Health Epidemic SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Editorial Material ID METABOLIC SYNDROME; FRUCTOSE; DISEASE C1 [Kang, Jing X.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Lab Lipid Med & Technol LLMT, 149,13th St,Room 4001, Charlestown, MA 02129 USA. EM kang.jing@mgh.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 EI 1661-6758 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2014 VL 7 IS 4-6 BP 188 EP 190 DI 10.1159/000375471 PG 3 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA CK3RS UT WOS:000356133800002 PM 25766253 ER PT B AU Willis, D Perry, DJ LaCoursiere-Zucchero, T Grace, P AF Willis, Danny Perry, Donna J. LaCoursiere-Zucchero, Terri Grace, Pamela BE Kagan, PN Smith, MC Chinn, PL TI Facilitating Humanization Liberating the Profession of Nursing from Institutional Confinement on Behalf of Social Justice SO PHILOSOPHIES AND PRACTICES OF EMANCIPATORY NURSING: SOCIAL JUSTICE AS PRAXIS SE Routledge Studies in Health and Social Welfare LA English DT Article; Book Chapter ID HEALTH; CRITIQUE; PATTERNS C1 [Willis, Danny] Boston Coll, William F Connell Sch Nursing, Chestnut Hill, MA 02167 USA. [Perry, Donna J.; LaCoursiere-Zucchero, Terri] Univ Massachusetts, Grad Sch Nursing, Worcester, MA 01605 USA. [Perry, Donna J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Perry, Donna J.] Ctr Nonviolent Solut Board Directors, Worcester, MA USA. [LaCoursiere-Zucchero, Terri] Bedford VA Med Ctr, Bedford, MA USA. [Grace, Pamela] Boston Coll, Nursing & Eth, Chestnut Hill, MA 02167 USA. RP Willis, D (reprint author), Boston Coll, William F Connell Sch Nursing, Chestnut Hill, MA 02167 USA. NR 37 TC 2 Z9 2 U1 1 U2 1 PU ROUTLEDGE PI ABINGDON PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND BN 978-0-203-06909-7; 978-0-415-65953-6 J9 ROUT STUD HLTH SOC W PY 2014 VL 11 BP 251 EP 265 PG 15 WC Nursing; Social Issues SC Nursing; Social Issues GA BC4XA UT WOS:000352985300020 ER PT B AU Martindale, RG McClave, SA Warren, M Desai, S AF Martindale, Robert G. McClave, Stephen A. Warren, Malissa Desai, Svetang BE Schiffrin, EJ Marteau, P Brassart, D TI Influence of the Intestinal Microbiota on the Critically Ill Patient SO INTESTINAL MICROBIOTA IN HEALTH AND DISEASE: MODERN CONCEPTS LA English DT Article; Book Chapter ID CLOSTRIDIUM-DIFFICILE DISEASE; VENTILATOR-ASSOCIATED PNEUMONIA; PLACEBO-CONTROLLED TRIAL; SEVERE ACUTE-PANCREATITIS; MULTIPLE ORGAN FAILURE; INTENSIVE-CARE-UNIT; GUT MICROBIOTA; DOUBLE-BLIND; SACCHAROMYCES-BOULARDII; PSEUDOMONAS-AERUGINOSA C1 [Martindale, Robert G.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [McClave, Stephen A.] Univ Louisville, Louisville, KY 40202 USA. [Warren, Malissa] Portland VA Med Ctr, Portland, OR 97207 USA. [Desai, Svetang] Duke Univ, Gastroenterol Sect, Duke Clin 2G 2H, Durham, NC 27710 USA. RP Martindale, RG (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd,L223A, Portland, OR 97239 USA. EM martindr@ohsu.edu; Stephen.mcclave@louisville.edu; Malissa.warren@va.gov; Svetang@gmail.com NR 56 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 978-1-4822-2677-5; 978-1-4822-2676-8 PY 2014 BP 293 EP 306 PG 14 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA BC8FY UT WOS:000355632100014 ER PT J AU Sawa, T Shimizu, M Moriyama, K Wiener-Kronish, JP AF Sawa, Teiji Shimizu, Masaru Moriyama, Kiyoshi Wiener-Kronish, Jeanine P. TI Association between Pseudomonas aeruginosa type III secretion, antibiotic resistance, and clinical outcome: a review SO CRITICAL CARE LA English DT Review ID VENTILATOR-ASSOCIATED PNEUMONIA; HOSPITAL-ACQUIRED PNEUMONIA; ALVEOLAR EPITHELIAL INJURY; LIPID ACYL HYDROLASE; EXOENZYME-S REGULON; ANTI-PCRV ANTIBODY; CYSTIC-FIBROSIS; CYTOTOXIN EXOU; PROTEIN SECRETION; PHOSPHOLIPASE-ACTIVITY AB Pseudomonas aeruginosa uses a complex type III secretion system to inject the toxins ExoS, ExoT, ExoU, and ExoY into the cytosol of target eukaryotic cells. This system is regulated by the exoenzyme S regulon and includes the transcriptional activator ExsA. Of the four toxins, ExoU is characterized as the major virulence factor responsible for alveolar epithelial injury in patients with P. aeruginosa pneumonia. Virulent strains of P. aeruginosa possess the exoU gene, whereas non-virulent strains lack this particular gene. The mechanism of virulence for the exoU(+) genotype relies on the presence of a pathogenic gene cluster (PAPI-2) encoding exoU and its chaperone, spcU. The ExoU toxin has a patatin-like phospholipase domain in its N-terminal, exhibits phospholipase A(2) activity, and requires a eukaryotic cell factor for activation. The C-terminal of ExoU has a ubiquitinylation mechanism of activation. This probably induces a structural change in enzymatic active sites required for phospholipase A(2) activity. In P. aeruginosa clinical isolates, the exoU(+) genotype correlates with a fluoroquinolone resistance phenotype. Additionally, poor clinical outcomes have been observed in patients with pneumonia caused by exoU(+)-fluoroquinolone-resistant isolates. Therefore, the potential exists to improve clinical outcomes in patients with P. aeruginosa pneumonia by identifying virulent and antimicrobial drug-resistant strains through exoU genotyping or ExoU protein phenotyping or both. C1 [Sawa, Teiji; Shimizu, Masaru] Kyoto Prefectural Univ Med, Dept Anesthesiol, Kamigyo Ku, Kyoto 6028566, Japan. [Moriyama, Kiyoshi] Kyorin Univ, Sch Med, Dept Anesthesiol, Mitaka, Tokyo 1818611, Japan. [Wiener-Kronish, Jeanine P.] Harvard Med Univ, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Sawa, T (reprint author), Kyoto Prefectural Univ Med, Dept Anesthesiol, Kamigyo Ku, 465 Kajii Cho, Kyoto 6028566, Japan. EM anesth@koto.kpu-m.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology (Japan) [24390403] FX This work was supported by a Grant-in-Aid for Scientific Research (KAKENHI #24390403) from the Ministry of Education, Culture, Sports, Science and Technology (Japan) to TS. NR 99 TC 15 Z9 15 U1 2 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2014 VL 18 IS 6 AR 668 DI 10.1186/s13054-014-0668-9 PG 11 WC Critical Care Medicine SC General & Internal Medicine GA CI9LV UT WOS:000355092500081 PM 25672496 ER PT B AU Evans, KC Banzett, RB AF Evans, Karleyton C. Banzett, Robert B. BE Mahler, DA ODonnell, DE TI Neuroimaging of Dyspnea SO DYSPNEA: MECHANISMS, MEASUREMENT, AND MANAGEMENT, 3RD EDITION LA English DT Article; Book Chapter ID CENTRAL HYPOVENTILATION SYNDROME; EVENT-RELATED FMRI; INTRINSIC FUNCTIONAL CONNECTIVITY; CEREBRAL-BLOOD-FLOW; END-TIDAL CO2; HUMAN BRAIN; AIR HUNGER; VOLITIONAL INSPIRATION; HEMODYNAMIC-RESPONSE; AFFECTIVE DIMENSION C1 [Evans, Karleyton C.] Harvard Univ, Sch Med, Dept Psychiat, Psychiat Neurosci Div,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Banzett, Robert B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02215 USA. RP Evans, KC (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Psychiat Neurosci Div,Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 113 TC 1 Z9 1 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 978-1-4822-0874-0; 978-1-4822-0869-6 PY 2014 BP 11 EP 24 D2 10.1201/b16363 PG 14 WC Respiratory System SC Respiratory System GA BC5HW UT WOS:000353291600004 ER PT J AU Roberts, LD AF Roberts, Lee D. BE Jones, OAH TI Type 2 Diabetes Mellitus and The Metabolic Syndrome SO METABOLOMICS AND SYSTEMS BIOLOGY IN HUMAN HEALTH AND MEDICINE LA English DT Article; Book Chapter ID CORONARY-HEART-DISEASE; GLUCOSE-TOLERANCE TEST; C-REACTIVE PROTEIN; INSULIN-RESISTANCE; FASTING GLUCOSE; CARDIOVASCULAR-DISEASE; PREMATURE ADRENARCHE; RISK; SENSITIVITY; OBESITY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Roberts, LD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM lee.roberts@mrc-hnr.cam.ac.uk NR 61 TC 1 Z9 1 U1 1 U2 1 PU CABI PUBLISHING-C A B INT PI WALLINGFORD PA CABI PUBLISHING, WALLINGFORD 0X10 8DE, OXON, ENGLAND BN 978-1-78064-200-0 PY 2014 BP 141 EP 156 D2 10.1079/9781780642000.0000 PG 16 WC Biology SC Life Sciences & Biomedicine - Other Topics GA BC7WB UT WOS:000355229900009 ER PT S AU Lee, SH Hayano, K Sahani, DV Zhu, AX Yoshida, H AF Lee, Sang Ho Hayano, Koichi Sahani, Dushyant V. Zhu, Andrew X. Yoshida, Hiroyuki BE Yoshida, H Nappi, JJ Saini, S TI Parameter Comparison Between Fast-Water-Exchange-Limit-Constrained Standard and Water-Exchange-Modified Dual-Input Tracer Kinetic Models for DCE-MRI in Advanced Hepatocellular Carcinoma SO ABDOMINAL IMAGING: COMPUTATIONAL AND CLINICAL APPLICATIONS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 6th International Workshop on Abdominal Imaging (ABDI) - Computational and Clinical Applications CY SEP 14, 2014 CL Cambridge, MA DE Hepatocellular carcinoma; Dual-input tracer kinetic analysis; Water exchange; Dynamic contrast-enhanced MRI ID CONTRAST-ENHANCED MRI; IN-VIVO; BLOOD-FLOW; PERMEABILITY; DIFFUSION; MUSCLE; VOLUME; CT AB Dynamic contrast-enhanced MRI (DCE-MRI) data have often been analyzed using classic standard tracer kinetic models that assume a fast-exchange limit (FXL) of water. Recently, it has been demonstrated that deviations from the FXL model occurs when contrast agent arrives at the target tissue. However, no systematic analysis has been reported for the liver tumor with dual blood supply. In this study, we compared kinetic parameter estimates from DCE-MRI in advanced hepatocellular carcinoma that have the same physiological meaning between five different FXL standard dual-input tracer kinetic models and their corresponding water-exchange-modified (WX) versions. Kinetic parameters were estimated by fitting data to analytic solutions of five different FXL models and their WX versions based on a full two-site-exchange model for transcytolemmal water exchange or a full three-site-two-exchange model for transendothelial and transcytolemmal water exchange. Results suggest that parameter values differ substantially between the FXL standard and WX tracer kinetic models, indicating that DCE-MRI data are water-exchange-sensitive. C1 [Lee, Sang Ho; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, Boston, MA 02114 USA. [Lee, Sang Ho; Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hayano, Koichi; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med,Dept Med,Div Hematol & Oncol, Boston, MA 02114 USA. [Zhu, Andrew X.] Dana Farber Partners Canc Care, Boston, MA 02114 USA. RP Lee, SH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM lee.sangho@mgh.harvard.edu; khayano@partners.org; dsahani@partners.org; azhu@partners.org; yoshida.hiro@mgh.harvard.edu RI Lee, Sang Ho/B-9149-2017 OI Lee, Sang Ho/0000-0002-4634-4904 NR 29 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-13692-9; 978-3-319-13691-2 J9 LECT NOTES COMPUT SC PY 2014 VL 8676 BP 33 EP 47 DI 10.1007/978-3-319-13692-9_4 PG 15 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BC6ZT UT WOS:000354696800004 ER PT S AU Lee, SH Hayano, K Sahani, DV Zhu, AX Yoshida, H AF Lee, Sang Ho Hayano, Koichi Sahani, Dushyant V. Zhu, Andrew X. Yoshida, Hiroyuki BE Yoshida, H Nappi, JJ Saini, S TI Kinetic Textural Biomarker for Predicting Survival of Patients with Advanced Hepatocellular Carcinoma After Antiangiogenic Therapy by Use of Baseline First-Pass Perfusion CT SO ABDOMINAL IMAGING: COMPUTATIONAL AND CLINICAL APPLICATIONS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 6th International Workshop on Abdominal Imaging (ABDI) - Computational and Clinical Applications CY SEP 14, 2014 CL Cambridge, MA DE Hepatocellular carcinoma; Antiangiogenic treatment; Kinetic texture; Perfusion CT ID COLORECTAL-CANCER; INITIAL-EXPERIENCE; ENHANCEMENT; BEVACIZUMAB; PARAMETERS; TRACER; TISSUE; LIVER; MODEL; MRI AB Previous texture analysis studies of liver CT images have shown the potential to achieve hepatic malignancy or predict overall survival (OS). However, to date, most studies have mainly focused on assessing texture features of the non-contrast CT or portal-phase image in the dynamic contrast-enhanced CT sequence. The aim of this study was to quantify texture features of physiologically-based kinetic parametric images, and to develop prognostic kinetic textural biomarkers for 1-year survival (1YS) and OS in patients with advanced hepatocellular carcinoma (HCC) following antiangiogenic therapy in comparison among five different tracer kinetic models. Mean, standard deviation, coefficient of variation, skewness, and kurtosis of the pixel distribution histogram within HCC were derived from baseline first-pass perfusion CT parameters. Results suggest that texture analysis of kinetic parametric images can provide better chances of finding effective prognostic biomarkers for the prediction of survival than a mean value analysis alone. C1 [Lee, Sang Ho; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, Boston, MA 02114 USA. [Lee, Sang Ho; Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hayano, Koichi; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med,Dept Med,Div Hematol & Oncol, Boston, MA 02114 USA. [Zhu, Andrew X.] Dana Farber Partners Canc Care, Boston, MA 02114 USA. RP Lee, SH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM lee.sangho@mgh.harvard.edu; khayano@partners.org; dsahani@partners.org; azhu@partners.org; yoshida.hiro@mgh.harvard.edu RI Lee, Sang Ho/B-9149-2017 OI Lee, Sang Ho/0000-0002-4634-4904 NR 24 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-13692-9; 978-3-319-13691-2 J9 LECT NOTES COMPUT SC PY 2014 VL 8676 BP 48 EP 61 DI 10.1007/978-3-319-13692-9_5 PG 14 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BC6ZT UT WOS:000354696800005 ER PT S AU Lee, SH Ryu, Y Hayano, K Yoshida, H AF Lee, Sang Ho Ryu, Yasuji Hayano, Koichi Yoshida, Hiroyuki BE Yoshida, H Nappi, JJ Saini, S TI Feasibility of Single-Input Tracer Kinetic Modeling with Continuous-Time Formalism in Liver 4-Phase Dynamic Contrast-Enhanced CT SO ABDOMINAL IMAGING: COMPUTATIONAL AND CLINICAL APPLICATIONS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 6th International Workshop on Abdominal Imaging (ABDI) - Computational and Clinical Applications CY SEP 14, 2014 CL Cambridge, MA DE Continuous-time tracer kinetic modeling; Bolus arrival time; Vascular transport operator; Four-phase dynamic contrast-enhanced CT ID CAPILLARY-PERMEABILITY; PERFUSION PARAMETERS; COMPUTED-TOMOGRAPHY; HEPATIC METASTASES; BLOOD-FLOW; MRI AB The modeling of tracer kinetics with use of low-temporal-resolution data is of central importance for patient dose reduction in dynamic contrast-enhanced CT (DCE-CT) study. Tracer kinetic models of the liver vary according to the physiologic assumptions imposed on the model, and they can substantially differ in the ways how the input for blood supply and tissue compartments are modeled. In this study, single-input flow-limited (FL), Tofts-Kety (TK), extended TK (ETK), Hayton-Brady (HB), two compartment exchange (2CX), and adiabatic approximation to the tissue homogeneity (AATH) models were applied to the analysis of liver 4-phase DCE-CT data with fully continuous-time parameter formulation, including the bolus arrival time. The bolus arrival time for the 2CX and AATH models was described by modifying the vascular transport operator theory. Initial results indicate that single-input tracer kinetic modeling is feasible for distinguishing between hepatocellular carcinoma and normal liver parenchyma. C1 [Lee, Sang Ho; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, Boston, MA 02114 USA. [Lee, Sang Ho; Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hayano, Koichi] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Ryu, Yasuji] Kanazawa Univ, Grad Sch Med Sci, Dept Radiol, Kanazawa, Ishikawa 9208641, Japan. RP Lee, SH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM lee.sangho@mgh.harvard.edu; yryu-kanazawa@umin.ac.jp; khayano@partners.org; yoshida.hiro@mgh.harvard.edu RI Lee, Sang Ho/B-9149-2017 OI Lee, Sang Ho/0000-0002-4634-4904 NR 21 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 978-3-319-13692-9; 978-3-319-13691-2 J9 LECT NOTES COMPUT SC PY 2014 VL 8676 BP 62 EP 73 DI 10.1007/978-3-319-13692-9_6 PG 12 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BC6ZT UT WOS:000354696800006 ER PT S AU Nappi, JJ Tachibana, R Regge, D Yoshida, H AF Naeppi, Janne J. Tachibana, Rie Regge, Daniele Yoshida, Hiroyuki BE Yoshida, H Nappi, JJ Saini, S TI Information-Preserving Pseudo-Enhancement Correction for Non-Cathartic Low-Dose Dual-Energy CT Colonography SO ABDOMINAL IMAGING: COMPUTATIONAL AND CLINICAL APPLICATIONS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 6th International Workshop on Abdominal Imaging (ABDI) - Computational and Clinical Applications CY SEP 14, 2014 CL Cambridge, MA DE CT colonography; Pseudo-enhancement; Dual-energy CT; Virtual colonoscopy ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; PSEUDOENHANCEMENT; ATTENUATION; REDUCTION; SCANNER; POLYPS AB In CT colonography (CTC), orally administered positive-contrast fecal-tagging agents can cause artificial elevation of the observed radiodensity of adjacent soft tissue. Such pseudo-enhancement makes it challenging to differentiate polyps and folds reliably from tagged materials, and it is also present in dual-energy CTC (DE-CTC). We developed a method that corrects for pseudo-enhancement on DE-CTC images without distorting the dual-energy information contained in the data. A pilot study was performed to evaluate the effect of the method visually and quantitatively by use of clinical non-cathartic low-dose DE-CTC data from 10 patients including 13 polyps covered partially or completely by iodine-based fecal tagging. The results indicate that the proposed method can be used to reduce the pseudo-enhancement distortion of DE-CTC images without losing material-specific dual-energy information. The method has potential application in improving the accuracy of automated image-processing applications, such as computer-aided detection and virtual bowel cleansing in CTC. C1 [Naeppi, Janne J.; Tachibana, Rie; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, Boston, MA 02114 USA. [Naeppi, Janne J.; Tachibana, Rie; Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Regge, Daniele] Inst Canc Res & Treatment, I-10060 Turin, Italy. RP Nappi, JJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM janne.nappi@mgh.harvard.edu; rtachibana@mgh.harvard.edu; yoshida.hiro@mgh.harvard.edu NR 20 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-13692-9; 978-3-319-13691-2 J9 LECT NOTES COMPUT SC PY 2014 VL 8676 BP 159 EP 168 DI 10.1007/978-3-319-13692-9_15 PG 10 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BC6ZT UT WOS:000354696800015 ER PT S AU Tachibana, R Nappi, JJ Yoshida, H AF Tachibana, Rie Naeppi, Janne J. Yoshida, Hiroyuki BE Yoshida, H Nappi, JJ Saini, S TI Application of Pseudo-enhancement Correction to Virtual Monochromatic CT Colonography SO ABDOMINAL IMAGING: COMPUTATIONAL AND CLINICAL APPLICATIONS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 6th International Workshop on Abdominal Imaging (ABDI) - Computational and Clinical Applications CY SEP 14, 2014 CL Cambridge, MA DE Dual-energy CT; Virtual monochromatic imaging; Pseudo-enhancement correction; CT colonography ID COMPUTED-TOMOGRAPHY COLONOGRAPHY; ATTENUATION AB In CT colonography, orally administered positive-contrast fecal-tagging agents are used for differentiating residual fluid and feces from true lesions. However, the presence of high-density tagging agent in the colon can introduce erroneous artifacts, such as local pseudo-enhancement and beam-hardening, on the reconstructed CT images, thereby complicating reliable detection of soft-tissue lesions. In dual-energy CT colonography, such image artifacts can be reduced by the calculation of virtual monochromatic CT images, which provide more accurate quantitative attenuation measurements than conventional single-energy CT colonography. In practice, however, virtual monochromatic images may still contain some pseudo-enhancement artifacts, and efforts to minimize radiation dose may enhance such artifacts. In this study, we evaluated the effect of image-based pseudo-enhancement post-correction on virtual monochromatic images in standard-dose and low-dose dual-energy CT colonography. The mean CT values of the virtual monochromatic standard-dose CT images of 51 polyps and those of the virtual monochromatic low-dose CT images of 20 polyps were measured without and with the pseudo-enhancement correction. Statistically significant differences were observed between uncorrected and pseudo-enhancement-corrected images of polyps covered by fecal tagging in standard-dose CT (p < 0.001) and in low-dose CT (p < 0.05). The results indicate that image-based pseudo-enhancement post-correction can be useful for optimizing the performance of image-processing applications in virtual monochromatic CT colonography. C1 [Tachibana, Rie] Harvard Univ, Sch Med, Dept Radiol, Imaging Res 3D, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Tachibana, R (reprint author), Harvard Univ, Sch Med, Dept Radiol, Imaging Res 3D, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM rtachibana@mgh.harvard.edu; janne.nappi@mgh.harvard.edu; yoshida.hiro@mgh.harvard.edu NR 14 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-13692-9; 978-3-319-13691-2 J9 LECT NOTES COMPUT SC PY 2014 VL 8676 BP 169 EP 178 DI 10.1007/978-3-319-13692-9_16 PG 10 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BC6ZT UT WOS:000354696800016 ER PT S AU Yip, M Jin, R Nakajima, HH Stankovic, KM Chandrakasan, AP AF Yip, Marcus Jin, Rui Nakajima, Hideko Heidi Stankovic, Konstantina M. Chandrakasan, Anantha P. GP IEEE TI A Fully-Implantable Cochlear Implant SoC with Piezoelectric Middle-Ear Sensor and Energy-Efficient Stimulation in 0.18 mu m HVCMOS SO 2014 IEEE INTERNATIONAL SOLID-STATE CIRCUITS CONFERENCE DIGEST OF TECHNICAL PAPERS (ISSCC) SE IEEE International Solid State Circuits Conference LA English DT Proceedings Paper CT 1st IEEE International Solid-State Circuits Conference (ISSCC) CY FEB 09-13, 2014 CL San Francisco, CA SP IEEE C1 [Yip, Marcus; Jin, Rui; Chandrakasan, Anantha P.] MIT, Cambridge, MA 02139 USA. [Nakajima, Hideko Heidi; Stankovic, Konstantina M.] Harvard Univ, Sch Med, Boston, MA USA. [Nakajima, Hideko Heidi; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Yip, M (reprint author), MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. NR 6 TC 1 Z9 1 U1 1 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0193-6530 BN 978-1-4799-0918-6 J9 ISSCC DIG TECH PAP I PY 2014 VL 57 BP 312 EP + PG 3 WC Engineering, Electrical & Electronic SC Engineering GA BC5XL UT WOS:000353615000126 ER PT S AU Bandyopadhyay, S Mercier, PP Lysaght, AC Stankovic, KM Chandrakasan, AP AF Bandyopadhyay, Saurav Mercier, Patrick P. Lysaght, Andrew C. Stankovic, Konstantina M. Chandrakasan, Anantha P. GP IEEE TI A 1.1nW Energy Harvesting System with 544pW Quiescent Power for Next-Generation Implants SO 2014 IEEE INTERNATIONAL SOLID-STATE CIRCUITS CONFERENCE DIGEST OF TECHNICAL PAPERS (ISSCC) SE IEEE International Solid State Circuits Conference LA English DT Proceedings Paper CT 1st IEEE International Solid-State Circuits Conference (ISSCC) CY FEB 09-13, 2014 CL San Francisco, CA SP IEEE C1 [Bandyopadhyay, Saurav; Mercier, Patrick P.; Chandrakasan, Anantha P.] MIT, Cambridge, MA 02139 USA. [Mercier, Patrick P.] Univ Calif San Diego, San Diego, CA 92103 USA. [Lysaght, Andrew C.; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Stankovic, Konstantina M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Bandyopadhyay, S (reprint author), Texas Instruments Inc, Dallas, TX 75243 USA. NR 5 TC 3 Z9 3 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0193-6530 BN 978-1-4799-0918-6 J9 ISSCC DIG TECH PAP I PY 2014 VL 57 BP 396 EP + PG 3 WC Engineering, Electrical & Electronic SC Engineering GA BC5XL UT WOS:000353615000163 ER PT B AU DeAngelo, DJ AF DeAngelo, Daniel J. BE Abutalib, SA Markman, M TI Management of T-cell acute lymphoblastic leukemia SO CANCER CONSULT: EXPERTISE FOR CLINICAL PRACTICE LA English DT Article; Book Chapter ID GROUP-B; ADULTS; CANCER C1 [DeAngelo, Daniel J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [DeAngelo, Daniel J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP DeAngelo, DJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-58919-9; 978-1-118-58921-2 PY 2014 BP 29 EP 34 D2 10.1002/9781118589199 PG 6 WC Oncology SC Oncology GA BC3IR UT WOS:000351672800005 ER PT B AU Jacobson, CA LaCasce, AS AF Jacobson, Caron A. LaCasce, Ann S. BE Abutalib, SA Markman, M TI Gray zone lymphoma SO CANCER CONSULT: EXPERTISE FOR CLINICAL PRACTICE LA English DT Article; Book Chapter C1 [Jacobson, Caron A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [LaCasce, Ann S.] Harvard Univ, Sch Med, Dana Farber Partners CancerCare, Hematol Med Oncol, Boston, MA USA. RP Jacobson, CA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-58919-9; 978-1-118-58921-2 PY 2014 BP 290 EP 294 D2 10.1002/9781118589199 PG 5 WC Oncology SC Oncology GA BC3IR UT WOS:000351672800046 ER PT B AU Blondin, NA Baehring, JM Hochberg, FH AF Blondin, Nicholas A. Baehring, Joachim M. Hochberg, Fred H. BE Abutalib, SA Markman, M TI Primary CNS lymphoma SO CANCER CONSULT: EXPERTISE FOR CLINICAL PRACTICE LA English DT Article; Book Chapter ID STEM-CELL TRANSPLANTATION; PROGNOSIS C1 [Blondin, Nicholas A.; Baehring, Joachim M.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. [Baehring, Joachim M.] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA. [Baehring, Joachim M.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. [Hochberg, Fred H.] Massachusetts Gen Hosp, Neurol, Boston, MA 02114 USA. RP Blondin, NA (reprint author), Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-58919-9; 978-1-118-58921-2 PY 2014 BP 308 EP 315 D2 10.1002/9781118589199 PG 8 WC Oncology SC Oncology GA BC3IR UT WOS:000351672800049 ER PT B AU Varga, C Prada, CP Anderson, K Richardson, P AF Varga, Cindy Prada, Claudia Paba Anderson, Kenneth Richardson, Paul BE Abutalib, SA Markman, M TI Treatment of multiple myeloma SO CANCER CONSULT: EXPERTISE FOR CLINICAL PRACTICE LA English DT Article; Book Chapter ID STEM-CELL TRANSPLANTATION; BORTEZOMIB; DEXAMETHASONE; THERAPY C1 [Varga, Cindy; Prada, Claudia Paba; Richardson, Paul] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Anderson, Kenneth] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Varga, C (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-58919-9; 978-1-118-58921-2 PY 2014 BP 358 EP 365 D2 10.1002/9781118589199 PG 8 WC Oncology SC Oncology GA BC3IR UT WOS:000351672800057 ER PT B AU Soiffer, RJ AF Soiffer, Robert J. BE Abutalib, SA Markman, M TI Preparative regimens in allogeneic hematopoietic cell transplantation for malignant hematological diseases SO CANCER CONSULT: EXPERTISE FOR CLINICAL PRACTICE LA English DT Article; Book Chapter ID BUSULFAN; LEUKEMIA; TRIAL C1 Dana Farber Canc Inst, Hematol Malignancies Dept, Stem Cell Bone Marrow Transplantat Program, Boston, MA 02115 USA. RP Soiffer, RJ (reprint author), Dana Farber Canc Inst, Hematol Malignancies Dept, Stem Cell Bone Marrow Transplantat Program, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-58919-9; 978-1-118-58921-2 PY 2014 BP 417 EP 420 D2 10.1002/9781118589199 PG 4 WC Oncology SC Oncology GA BC3IR UT WOS:000351672800066 ER PT B AU O'Donnell, EK Kantoff, P AF O'Donnell, Elizabeth K. Kantoff, Philip BE Abutalib, SA Markman, M TI Medical management of prostate cancer SO CANCER CONSULT: EXPERTISE FOR CLINICAL PRACTICE LA English DT Article; Book Chapter C1 [O'Donnell, Elizabeth K.; Kantoff, Philip] Dana Farber Canc Inst Boston, Boston, MA 02115 USA. RP O'Donnell, EK (reprint author), Dana Farber Canc Inst Boston, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-58919-9; 978-1-118-58921-2 PY 2014 BP 638 EP 644 D2 10.1002/9781118589199 PG 7 WC Oncology SC Oncology GA BC3IR UT WOS:000351672800099 ER PT B AU Dalton, E Schneider, K AF Dalton, Emily Schneider, Kathy BE Abutalib, SA Markman, M TI When to suspect hereditary cancer syndromes SO CANCER CONSULT: EXPERTISE FOR CLINICAL PRACTICE LA English DT Article; Book Chapter C1 [Dalton, Emily] Ambry Genet, Aliso Viego, CA 92656 USA. [Schneider, Kathy] Dana Farber Canc Inst, Canc Genet & Prevent Program, Boston, MA 02115 USA. RP Dalton, E (reprint author), Ambry Genet, Aliso Viego, CA 92656 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-58919-9; 978-1-118-58921-2 PY 2014 BP 795 EP 799 D2 10.1002/9781118589199 PG 5 WC Oncology SC Oncology GA BC3IR UT WOS:000351672800124 ER PT B AU Schneider, K Dalton, E AF Schneider, Kathy Dalton, Emily BE Abutalib, SA Markman, M TI Hereditary breast cancer syndromes SO CANCER CONSULT: EXPERTISE FOR CLINICAL PRACTICE LA English DT Article; Book Chapter C1 [Schneider, Kathy] Dana Farber Canc Inst, Canc Genet & Prevent Program, Boston, MA 02115 USA. [Dalton, Emily] Ambry Genet, Boston, MA USA. RP Schneider, K (reprint author), Dana Farber Canc Inst, Canc Genet & Prevent Program, Boston, MA 02115 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-58919-9; 978-1-118-58921-2 PY 2014 BP 800 EP 803 D2 10.1002/9781118589199 PG 4 WC Oncology SC Oncology GA BC3IR UT WOS:000351672800125 ER PT B AU Shannon, KM Chung, DC AF Shannon, Kristen M. Chung, Daniel C. BE Abutalib, SA Markman, M TI Genetic testing in gastrointestinal tumors SO CANCER CONSULT: EXPERTISE FOR CLINICAL PRACTICE LA English DT Article; Book Chapter ID COLORECTAL-CANCER; LYNCH SYNDROME C1 [Shannon, Kristen M.] Massachusetts Gen Hosp, Ctr Canc, Genet Program, Boston, MA 02114 USA. [Chung, Daniel C.] Massachusetts Gen Hosp, Ctr Canc, Gastrointestinal Unit, Boston, MA USA. [Chung, Daniel C.] Massachusetts Gen Hosp, Ctr Canc, GI Canc Genet Program, Boston, MA USA. [Chung, Daniel C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Shannon, KM (reprint author), Massachusetts Gen Hosp, Ctr Canc, Genet Program, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-58919-9; 978-1-118-58921-2 PY 2014 BP 804 EP 809 D2 10.1002/9781118589199 PG 6 WC Oncology SC Oncology GA BC3IR UT WOS:000351672800126 ER PT B AU McDermott, S Blake, MA AF McDermott, Shaunagh Blake, Michael A. BE Abutalib, SA Markman, M TI PET scan in oncology SO CANCER CONSULT: EXPERTISE FOR CLINICAL PRACTICE LA English DT Article; Book Chapter ID LESIONS C1 [McDermott, Shaunagh; Blake, Michael A.] Massachusetts Gen Hosp, Dept Abdominal Imaging, Boston, MA 02114 USA. RP McDermott, S (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-58919-9; 978-1-118-58921-2 PY 2014 BP 835 EP 840 D2 10.1002/9781118589199 PG 6 WC Oncology SC Oncology GA BC3IR UT WOS:000351672800132 ER PT B AU Corsello, SM Connors, JM AF Corsello, Steven M. Connors, Jean Marie BE Abutalib, SA Markman, M TI Anticoagulation issues in oncology SO CANCER CONSULT: EXPERTISE FOR CLINICAL PRACTICE LA English DT Article; Book Chapter ID MOLECULAR-WEIGHT HEPARIN; RECURRENT VENOUS THROMBOEMBOLISM; CANCER-PATIENTS; THROMBOSIS; RISK C1 [Corsello, Steven M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Connors, Jean Marie] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Hematol Div, Boston, MA 02115 USA. [Corsello, Steven M.; Connors, Jean Marie] Harvard Univ, Sch Med, Boston, MA USA. RP Corsello, SM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-58919-9; 978-1-118-58921-2 PY 2014 BP 844 EP 850 D2 10.1002/9781118589199 PG 7 WC Oncology SC Oncology GA BC3IR UT WOS:000351672800134 ER PT B AU Lu, WD Rosenthal, DS AF Lu, Weidong Rosenthal, David S. BE Abutalib, SA Markman, M TI Integrative medicine in oncology SO CANCER CONSULT: EXPERTISE FOR CLINICAL PRACTICE LA English DT Article; Book Chapter ID BORTEZOMIB C1 [Lu, Weidong; Rosenthal, David S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02138 USA. [Lu, Weidong; Rosenthal, David S.] Dana Farber Canc Inst, Zakim Ctr Integrat Therapies, Boston, MA 02115 USA. RP Lu, WD (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02138 USA. RI Lu, Weidong/C-3844-2008 OI Lu, Weidong/0000-0003-2838-6307 NR 5 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-58919-9; 978-1-118-58921-2 PY 2014 BP 872 EP 878 D2 10.1002/9781118589199 PG 7 WC Oncology SC Oncology GA BC3IR UT WOS:000351672800138 ER PT B AU Johnson, LW Weinstock, RS AF Johnson, Lewis W. Weinstock, Ruth S. BE Lamster, IB TI Medical complications of diabetes mellitus SO DIABETES MELLITUS AND ORAL HEALTH: AN INTERPROFESSIONAL APPROACH LA English DT Article; Book Chapter ID NUTRITION EXAMINATION SURVEY; PLACEBO-CONTROLLED TRIAL; BLOOD-GLUCOSE CONTROL; CARDIOVASCULAR-DISEASE; RISK-FACTORS; MULTIFACTORIAL INTERVENTION; HEARING IMPAIRMENT; PRIMARY PREVENTION; INTENSIVE THERAPY; SURGERY PATIENTS C1 [Johnson, Lewis W.] SUNY Upstate Med Univ, Div Endocrinol Diabet & Metab, Med, Syracuse, NY 13210 USA. [Weinstock, Ruth S.] SUNY Upstate Med Univ, Div Endocrinol Diabet & Metab, Syracuse, NY 13210 USA. [Weinstock, Ruth S.] SUNY Upstate Med Univ, Clin Res Unit, Syracuse, NY 13210 USA. [Weinstock, Ruth S.] SUNY Upstate Med Univ, Joslin Diabet Ctr, Dept Med, Syracuse, NY 13210 USA. RP Johnson, LW (reprint author), SUNY Upstate Med Univ, Div Endocrinol Diabet & Metab, Med, Syracuse, NY 13210 USA. NR 76 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-37780-2; 978-1-118-86416-6 PY 2014 BP 45 EP 68 D2 10.1002/9781118887837 PG 24 WC Dentistry, Oral Surgery & Medicine; Endocrinology & Metabolism SC Dentistry, Oral Surgery & Medicine; Endocrinology & Metabolism GA BC3FZ UT WOS:000351620800004 ER PT B AU Kaur, H Weinstock, RS AF Kaur, Harpreet Weinstock, Ruth S. BE Lamster, IB TI Glycemic treatment of diabetes mellitus SO DIABETES MELLITUS AND ORAL HEALTH: AN INTERPROFESSIONAL APPROACH LA English DT Article; Book Chapter ID RANDOMIZED CONTROLLED-TRIAL; LIFE-STYLE INTERVENTION; SUBCUTANEOUS INSULIN INFUSION; IMPAIRED GLUCOSE-TOLERANCE; BETA-CELL FUNCTION; QUALITY-OF-LIFE; BLOOD-GLUCOSE; PREVENTION PROGRAM; SEVERE HYPOGLYCEMIA; COST-EFFECTIVENESS C1 [Kaur, Harpreet] Mercy Med Ctr North Iowa, Mercy Diabet Ctr, Endocrinol Diabet & Metab, Mason City, IA 50401 USA. [Weinstock, Ruth S.] SUNY Upstate Med Univ, Div Endocrinol Diabet & Metab, Syracuse, NY 13210 USA. [Weinstock, Ruth S.] SUNY Upstate Med Univ, Clin Res Unit, Syracuse, NY 13210 USA. [Weinstock, Ruth S.] SUNY Upstate Med Univ, Joslin Diabet Ctr, Dept Med, Syracuse, NY 13210 USA. RP Kaur, H (reprint author), Mercy Med Ctr North Iowa, Mercy Diabet Ctr, Endocrinol Diabet & Metab, Mason City, IA 50401 USA. NR 100 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-37780-2; 978-1-118-86416-6 PY 2014 BP 69 EP 95 D2 10.1002/9781118887837 PG 27 WC Dentistry, Oral Surgery & Medicine; Endocrinology & Metabolism SC Dentistry, Oral Surgery & Medicine; Endocrinology & Metabolism GA BC3FZ UT WOS:000351620800005 ER PT J AU Wong, JT Ling, M Patil, S Banerji, A Long, AD AF Wong, Johnson T. Ling, Morris Patil, Sarita Banerji, Aleena Long, Aidan TI Oxaliplatin Hypersensitivity: Evaluation, Implications of Skin Testing, and Desensitization SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Article DE Oxaliplatin; Carboplatin; Cisplatin; Hypersensitivity; Onset; Skin test; Continuous; Intravenous; Desensitization ID ADVANCED COLORECTAL-CANCER; OVARIAN NEOPLASM TRIAL; RISK-FACTORS; CARBOPLATIN HYPERSENSITIVITY; ADJUVANT CHEMOTHERAPY; COLD HYPERSENSITIVITY; CLINICAL-FEATURES; PROTOCOL; STRATIFICATION; FLUOROURACIL AB BACKGROUND: Oxaliplatin hypersensitivity (OXS) presents a challenge in the treatment of oxaliplatin-sensitive malignancies. OBJECTIVE: To analyze patient characteristics of patients with OXS, skin test results, and desensitization outcomes to optimize management. METHODS: Over 5 years, 48 patients with OXS were referred to the allergy/immunology unit at Massachusetts General Hospital. Their clinical reaction patterns were analyzed. Immediate hypersensitivity skin testing was used for risk stratification, and drug desensitizations were performed by using 3 related continuous intravenous protocols that were chosen based on clinical history, skin test reactivity, and the patients' previous desensitization outcomes. RESULTS: OXS occurred in both sexes, with mostly gastrointestinal-related tumors. Hypersensitivity reaction (HSR) onset had occurred during any course of therapy (course nos. 1-28), with a median onset at course no. 8. HSR to oxaliplatin was similar to those observed with cisplatin and carboplatin, including cutaneous, cardiovascular, pulmonary, and gastrointestinal symptoms. However, neurologic symptoms, including tingling, and systemic symptoms, including fever and chills, occurred more often in patients with OXS. Unique to OXS, 2 patients developed drug-induced thrombocytopenia; 1 patients also developed drug-induced hemolytic anemia. Skin testing was positive for the majority of patients with OXS (27/46 [59%]) and correlated with a greater likelihood of developing an HSR during subsequent desensitizations. We safely performed 200 desensitizations in 48 patients with OXS. CONCLUSION: OXS is common with much similarity to other platin agents but also have distinct differences in the onset of hypersensitivity, sex, tumor type, drug-induced hemolytic anemia, and drug-induced thrombocytopenia. Skin testing was helpful for risk stratification. All of the desensitizations were completed successfully. (C) 2013 American Academy of Allergy, Asthma & Immunology C1 Massachusetts Gen Hosp, Allergy & Immunol Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wong, JT (reprint author), Massachusetts Gen Hosp, Med, Cox 2, Boston, MA 02114 USA. EM jwong1@partners.org OI Ling, Morris/0000-0002-9657-8960 NR 26 TC 15 Z9 16 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD JAN-FEB PY 2014 VL 2 IS 1 BP 40 EP 45 DI 10.1016/j.jaip.2013.08.011 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA CH7EB UT WOS:000354197300006 PM 24565767 ER PT J AU Banerji, A Rudders, S Clark, S Wei, WH Long, ADA Camargo, CA AF Banerji, Aleena Rudders, Susan Clark, Sunday Wei, Wenhui Long, Aidan A. Camargo, Carlos A., Jr. TI Retrospective Study of Drug-induced Anaphylaxis Treated in the Emergency Department or Hospital: Patient Characteristics, Management, and 1-Year Follow-up SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Article DE Drug-induced anaphylaxis; Postdischarge care; Allergy; Emergency department; Hospitalization; Treatment guidelines; Hypersensitivity; Epinephrine; Atopy ID INHIBITOR-INDUCED ANGIOEDEMA; ALLERGY; RISK AB BACKGROUND: Drugs are a common cause of anaphylaxis, which is potentially life threatening. OBJECTIVE: We sought to describe US patients with an emergency department (ED) visit or hospitalization for drug-induced anaphylaxis (DIA), including postdischarge follow-upcare. METHODS: By using International Classification of Diseases, Ninth Revision codes in the MarketScan Database, we identified all patients with an ED visit and/or hospitalization for DIA between 2002 and 2008 (index date [initial ED visit and/or hospitalization). Inclusion required continuous full insurance coverage >= 1 year in the pre-and postindex period. We examined patient factors during the preindex period, characteristics of the index event, and outcomes during the postindex period. RESULTS: The cohort included 716 patients with an ED visit and/or hospitalization for DIA (mean age, 48 years; 71% women). Most patients (71%) were managed in the ED, and only 8% of the patients with DIA treated in the ED received epinephrine. For those admitted, patients were hospitalized for a median of 3 days, and 41% spent time in the intensive care unit. Cardiorespiratory failure occurred in 5% of the patients in the ED and 23% of the patients who were hospitalized. The patients with a concomitant allergic condition were more likely to see an allergist/immunologist than those without a concomitant allergic condition, but 82% did not receive any subsequent care with an allergist/immunologist in the 1 year after the ED visit and/or hospitalization for DIA. CONCLUSION: Drugs are a common, yet under-recognized, cause of anaphylaxis. Only a small number of patients with DIA received epinephrine in the ED or had subsequent care with an allergist/immunologist. These findings are novel and identify areas for improvement in the care of individuals with DIA. (C) 2013 American Academy of Allergy, Asthma & Immunology C1 [Banerji, Aleena; Long, Aidan A.; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Dept Med,Sch Med, Boston, MA USA. [Rudders, Susan] Brown Univ, Rhode Isl Hosp, Alpert Sch Med, Div Asthma & Allergy,Dept Pediat, Providence, RI 02903 USA. [Clark, Sunday] Weill Cornell Med Coll, Dept Emergency Med, New York, NY USA. [Wei, Wenhui] Sanofi US, Bridgewater, NJ USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Banerji, A (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, 55 Fruit St, Boston, MA 02114 USA. EM abanerji@partners.org FU Sanofi US; Novartis; Sanofi-Aventis; Dey/Mylan FX This study was funded by Sanofi US.; A. A. Long has received consultancy fees from Novartis as a member of an advisory board and has received royalties from UpToDate. W. Wei is an employee of Sanofi US. C. A. Camargo, Jr, has received research support from Sanofi-Aventis and has received consulting fees/honoraria from Dey/Mylan and Sanofi-Aventis. The rest of the authors declare that they have no relevant conflicts of interest. NR 31 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD JAN-FEB PY 2014 VL 2 IS 1 BP 46 EP 51 DI 10.1016/j.jaip.2013.08.012 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA CH7EB UT WOS:000354197300007 PM 24565768 ER PT J AU Lee, JH Traverso, G Schoellhammer, CM Blankschtein, D Langer, R Thomenius, KE Boning, DS Anthony, BW AF Lee, John H. Traverso, Giovanni Schoellhammer, Carl M. Blankschtein, Daniel Langer, Robert Thomenius, Kai E. Boning, Duane S. Anthony, Brian W. GP IEEE TI Towards Wireless Capsule Endoscopic Ultrasound (WCEU) 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 Wireless Capsule Endoscopy; Capsule Endoscopy; Small Intestine; Small Bowel; Endoscopic Ultrasound AB Wireless capsule endoscopy (WCE) has revolutionized the capacity for evaluation of the gastrointestinal (GI) tract. Although WCE provides high quality images of the GI tract, evaluation is limited to the mucosal surface. This work investigates feasibility and design considerations for wireless capsule endoscopic ultrasound (WCEU) that combines the benefits of WCE and ultrasound imaging. This work has two goals: (1) evaluate transducer designs appropriate for WCEU and (2) investigate whether peristalsis can produce sufficient contact to ensure acoustic coupling. Between mechanical scanning (MS) and side-looking array (SLA) designs, MS performs better for both imaging performance and system complexity. In vivo imaging in pigs demonstrates promising results, although the effect of peristalsis and resulting coverage needs further investigation and quantification. C1 [Lee, John H.; Traverso, Giovanni; Schoellhammer, Carl M.; Blankschtein, Daniel; Langer, Robert; Thomenius, Kai E.; Boning, Duane S.; Anthony, Brian W.] MIT, Cambridge, MA 02139 USA. [Traverso, Giovanni] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA 02115 USA. RP Lee, JH (reprint author), MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. OI Schoellhammer, Carl/0000-0001-6694-6761 NR 10 TC 2 Z9 2 U1 0 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-7049-0 PY 2014 BP 734 EP 737 DI 10.1109/ULTSYM.2014.0181 PG 4 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BC4NN UT WOS:000352792500181 ER PT S AU Liu, JB Reisner, AT Edla, S Reifman, J AF Liu, Jianbo Reisner, Andrew T. Edla, Shwetha Reifman, Jaques GP IEEE TI A Comparison of Alerting Strategies for Hemorrhage Identification during Prehospital Emergency Transport 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 ID TRAUMA PATIENTS AB Early and accurate identification of physiological abnormalities is one feature of intelligent decision support. The ideal analytic strategy for identifying pathological states would be highly sensitive and highly specific, with minimal latency. In the field of manufacturing, there are well-established analytic strategies for statistical process control, whereby aberrancies in a manufacturing process are detected by monitoring and analyzing the process output. These include simple thresholding, the sequential probability ratio test (SPRT), risk-adjusted SPRT, and the cumulative sum method. In this report, we applied these strategies to continuously monitored prehospital vital-sign data from trauma patients during their helicopter transport to level I trauma centers, seeking to determine whether one strategy would be superior. We found that different configurations of each alerting strategy yielded widely different performances in terms of sensitivity, specificity, and average time to alert. Yet, comparing the different investigational analytic strategies, we observed substantial overlap among their different configurations, without any one analytic strategy yielding distinctly superior performance. In conclusion, performance did not depend as much on the specific analytic strategy as much as the configuration of each strategy. This implies that any analytic strategy must be carefully configured to yield the optimal performance (i.e., the optimal balance between sensitivity, specificity, and latency) for a specific use case. Conversely, this also implies that an alerting strategy optimized for one use case (e.g., long prehospital transport times) may not necessarily yield performance data that are optimized for another clinical application (e.g., short prehospital transport times, intensive care units, etc.). C1 [Liu, Jianbo] USAMRMC, Dept Def, Biotechnol High Performance Comp Software Applica, TATRC, Ft Detrick, MD 21702 USA. [Reisner, Andrew T.; Edla, Shwetha; Reifman, Jaques] USAMRMC, TATRC, BHSAI, Ft Detrick, MD 21702 USA. [Reisner, Andrew T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Edla, S (reprint author), USAMRMC, TATRC, BHSAI, Ft Detrick, MD 21702 USA. EM jliu2@bhsai.org; areisner@partners.org; sedla@bhsai.org; jaques.reifman.civ@mail.mil NR 11 TC 0 Z9 0 U1 0 U2 0 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 2670 EP 2673 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044702163 ER PT S AU Smith, JB Reisner, AT Edla, S Liu, JB Liddle, S Reifman, J AF Smith, Jason B. Reisner, Andrew T. Edla, Shwetha Liu, Jianbo Liddle, Stephanie Reifman, Jaques GP IEEE TI A Platform for Real-time Acquisition and Analysis of Physiological Data in Hospital Emergency Departments 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 ID ALGORITHMS AB An opportunity exists for automated clinical decision support, in which raw source data from a conventional physiological monitoring system are continuously streamed to an independent analysis platform. Such a system would enable a wider range of functionality than offered by the source monitoring system. Although vendor solutions for this purpose are emerging, we developed our own system in order to control the expense and to permit forensic analysis of the internal core functionality of the system. In this report, we describe a platform that can provide decision support for trauma patients in an Emergency Department (ED). System evaluation spanned 39 days, and included a total of 2200 patient session hrs of real-time monitoring. We highlight the technical issues that we confronted, including protection of the core monitoring network, the real-time communication of electronic medical data, and the reliability of the real-time analysis. Detailing these nuanced technical issues may be valuable to other software developers or for those interested in investing in a vendor solution for similar functionality. C1 [Smith, Jason B.] USAMRMC, TATRC, Dept Def, Biotechnol High Performance Comp Software Applica, Ft Detrick, MD 21702 USA. [Reisner, Andrew T.; Edla, Shwetha; Liu, Jianbo; Reifman, Jaques] USAMRMC, BHSAI, TATRC, Ft Detrick, MD 21702 USA. [Reisner, Andrew T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Liddle, Stephanie] Massachusetts Gen Hosp, Dept Biomed Engn, Boston, MA 02114 USA. RP Reisner, AT (reprint author), USAMRMC, BHSAI, TATRC, Ft Detrick, MD 21702 USA. EM jsmith@bhsai.org; areisner@partners.org; sedla@bhsai.org; jliu2@bhsai.org; jaques.reifman.civ@mail.mil NR 11 TC 1 Z9 1 U1 0 U2 0 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 2678 EP 2681 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044702165 ER PT S AU Sinha, N Dauwels, J Wang, YJ Cash, SS Taylor, PN AF Sinha, Nishant Dauwels, Justin Wang, Yujiang Cash, Sydney S. Taylor, Peter N. GP IEEE TI An in silico approach for pre-surgical evaluation of an epileptic cortex 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 ID NETWORKS; MODEL AB Clinical evidence indicates that a third of patients with epilepsy are refractory to anti-epileptic drug treatment. For some of these patients better seizure control can be achieved by surgical treatment in which the seizure focus is localised and resected while avoiding injury to crucial cortical tissues. In this paper, non-seizure (interictal) epoch of electrographic recording was used to calculate the functional synchrony between different cortical regions. This synchrony measure was then used as the connectivity parameter in a computational model of transitions to a seizure like state. The seizure focus was localised using this model and the surgical intervention procedure was simulated. It was shown that the in silico removal of a subset of seizure focus can decrease the likelihood of a seizure in the model. The in silico results were also compared with the clinical outcomes and a convincing agreement was shown for five out of six patients; sixth being a counter-example. These methods may aid in the identification of the seizure onset zone using the interictal electrographic data. Moreover, it may facilitate neurosurgeons to investigate alternative cortical tissues to operate on if the seizure focus cannot be operated. C1 [Sinha, Nishant; Dauwels, Justin] Nanyang Technol Univ, Sch Elect & Elect Engn, Singapore 639798, Singapore. [Wang, Yujiang; Taylor, Peter N.] Newcastle Univ, Sch Comp Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Cash, Sydney S.] Massachusetts Gen Hosp, Cambridge, MA USA. [Cash, Sydney S.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Sinha, N (reprint author), Nanyang Technol Univ, Sch Elect & Elect Engn, Singapore 639798, Singapore. EM jdauwels@ntu.edu.sg OI Taylor, Peter/0000-0003-2144-9838 NR 16 TC 3 Z9 3 U1 0 U2 0 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 4884 EP 4887 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044704217 ER PT S AU Prashanth, R Roy, SD Mandal, PK Ghosh, S AF Prashanth, R. Roy, S. Dutta Mandal, P. K. Ghosh, S. GP IEEE TI Parkinson's disease detection using olfactory loss and REM sleep disorder features 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 ID SMELL IDENTIFICATION TEST; BEHAVIOR DISORDER; SCREENING QUESTIONNAIRE; SYMPTOMS; TESTS AB In Parkinson's disease, there exists a prodromal or a premotor phase characterized by symptoms like olfactory loss and sleep disorders, which may last for years or even decades before the onset of motor clinical symptoms. Diagnostic tools based on machine learning using these features can be very useful as they have the potential in early diagnosis of the disease. In the paper, we use olfactory loss feature from 40-item University of Pennsylvania Smell Identification Test (UPSIT) and Sleep behavior disorder feature from Rapid eye movement sleep Behavior Disorder Screening Questionnaire (RBDSQ), obtained from the Parkinson's Progression Marker's Initiative (PPMI) database, to develop automated diagnostic models using Support Vector Machine (SVM) and classification tree methods. The advantage of using UPSIT and RBDSQ is that they are quick, cheap, and can be self-administered. Results show that the models performed with high accuracy and sensitivity, and that they have the potential to aid in early diagnosis of Parkinson's disease. C1 [Prashanth, R.; Roy, S. Dutta] Indian Inst Technol Delhi, Dept Elect Engn, New Delhi, India. [Mandal, P. K.] Natl Brain Res Ctr, Neuroimaging & Neurospect Lab, Gurgaon, Haryana, India. [Ghosh, S.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Ghosh, S.] Harvard Univ, Sch Med, Boston, MA USA. RP Prashanth, R (reprint author), Indian Inst Technol Delhi, Dept Elect Engn, New Delhi, India. EM eez108051@ee.iitd.ac.in; sumantra@ee.iitd.ac.in; pravat.mandal@gmail.com; shantanu@nmr.mgh.harvard.edu NR 26 TC 1 Z9 2 U1 0 U2 0 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 5764 EP 5767 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044705188 ER PT S AU Park, YS Hochberg, LR Eskandar, EN Cash, SS Truccolo, W AF Park, Yun S. Hochberg, Leigh R. Eskandar, Emad N. Cash, Sydney S. Truccolo, Wilson GP IEEE TI Early Detection of Human Focal Seizures Based on Cortical Multiunit Activity 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 ID SUPPORT VECTOR MACHINES; EPILEPSY; EEG AB Approximately 50 million people in the world suffer from epileptic seizures. Reliable early seizure detection could bring significantly beneficial therapeutic alternatives. In recent decades, most approaches have relied on scalp EEG and intracranial EEG signals, but practical early detection for closed-loop seizure control remains challenging. In this study, we present preliminary analyses of an early detection approach based on intracortical neuronal multiunit activity (MUA) recorded from a 96-microelectrode array (MEA). The approach consists of (1) MUA detection from broadband field potentials recorded at 30 kHz by the MEA; (2) MUA feature extraction; (3) cost-sensitive support vector machine classification of ictal and interictal samples; and (4) Kalman-filtering postprocessing. MUA was here defined as the number of threshold crossing ( spike counts) applied to the 300 Hz - 6 kHz bandpass filtered local field potentials in 0.1 sec time windows. MUA features explored in this study included the mean, variance, and Fano-factor, computed across the MEA channels. In addition, we used the leading eigenvalues of MUA spatial and temporal correlation matrices computed in 1-sec moving time windows. We assessed the seizure detection approach on out-of-sample data from one-participant recordings with six seizure events and 4.73-hour interictal data. The proposed MUA-based detection approach yielded a 100% sensitivity (6/6) and no false positives, and a latency of 4.17 +/- 2.27 sec (mean +/- SD) with respect to ECoG-identified seizure onsets. These preliminary results indicate intracortical MUA may be a useful signal for early detection of human epileptic seizures. C1 [Park, Yun S.; Truccolo, Wilson] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Park, Yun S.; Truccolo, Wilson] Brown Univ, Brown Inst Brain Sci, Providence, RI 02912 USA. [Hochberg, Leigh R.; Truccolo, Wilson] Ctr Neurorestorat & Neurotechnol, Rehabil R&D Serv, Dept Vet Affairs, Providence, RI 02908 USA. [Hochberg, Leigh R.] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Hochberg, Leigh R.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hochberg, Leigh R.; Eskandar, Emad N.; Cash, Sydney S.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Park, YS (reprint author), Brown Univ, Dept Neurosci, Providence, RI 02912 USA. EM yun_sang_park@brown.edu; leigh_hochberg@brown.edu; eeskandar@partners.org; scash@partners.org; wilson_truccolo@brown.edu NR 14 TC 0 Z9 0 U1 1 U2 2 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 5796 EP 5799 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044705196 ER PT S AU Lee, SW Fried, SI AF Lee, Seung Woo Fried, Shelley I. GP IEEE TI The response of L5 pyramidal neurons of the PFC to magnetic stimulation from a micro-coil 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 ID MOTOR CORTEX AB Magnetic stimulation of the nervous system, e.g. transcranial magnetic stimulation (TMS), has been used both to unravel basic structure and function of the nervous system as well as to treat neurological diseases, i.e. clinical depression. Despite progress in both areas, ongoing advancements have been limited by a lack of understanding of the mechanism by which magnetic stimulation alters neural activity. Here, we report responses of cortical neurons to magnetic stimulation arising from a sub-millimeter coil. Cell attached patch clamp was used to record neural activity of layer 5/6 pyramidal neurons of the prefrontal cortex (PFC) in the in vitro mouse brain slice preparation. The fields arising from the small coil were quite different from those arising during clinical TMS but nevertheless allowed the responses of cortical neurons to magnetic stimulation to be probed. For example, the focal nature of induced fields allowed the sensitivity of different regions within targeted pyramidal neurons, e. g. apical dendrite, soma and axon hillock, to be compared. We found that PFC pyramidal neurons were not sensitive to single pulses of stimulation regardless of coil location. However, regions of the apical dendrite and proximal axon were both sensitive to repetitive stimulation as long as the orientation of the induced electric field was aligned with the long axis of the neuron. These results suggest that neurons of the PFC are sensitive to weak magnetic fields and further, that this type of approach may be useful for unraveling some of the mechanisms underlying TMS. C1 [Lee, Seung Woo; Fried, Shelley I.] Harvard Univ, Sch Med, Dept Neurosurg, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lee, SW (reprint author), Harvard Univ, Sch Med, Dept Neurosurg, Massachusetts Gen Hosp, MGH Thier 415,50 Blossom St, Boston, MA 02114 USA. EM Lee.Seungwoo@mgh.harvard.edu; Fried.Shelley@mgh.harvard.edu NR 14 TC 2 Z9 2 U1 3 U2 3 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 6125 EP 6128 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044706031 ER PT S AU Valenza, G Citi, L Scilingo, EP Barbieri, R AF Valenza, Gaetano Citi, Luca Scilingo, Enzo Pasquale Barbieri, Riccardo GP IEEE TI Tracking Instantaneous Entropy in Heartbeat Dynamics through Inhomogeneous Point-process Nonlinear Models 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 ID APPROXIMATE ENTROPY; RATE-VARIABILITY; COMPLEXITY AB Measures of entropy have been proved as powerful quantifiers of complex nonlinear systems, particularly when applied to stochastic series of heartbeat dynamics. Despite the remarkable achievements obtained through standard definitions of approximate and sample entropy, a time-varying definition of entropy characterizing the physiological dynamics at each moment in time is still missing. To this extent, we propose two novel measures of entropy based on the inhomogeneous point-process theory. The RR interval series is modeled through probability density functions (pdfs) which characterize and predict the time until the next event occurs as a function of the past history. Laguerre expansions of the Wiener-Volterra autoregressive terms account for the long-term nonlinear information. As the proposed measures of entropy are instantaneously defined through such probability functions, the proposed indices are able to provide instantaneous tracking of autonomic nervous system complexity. Of note, the distance between the time-varying phase-space vectors is calculated through the Kolmogorov-Smirnov distance of two pdfs. Experimental results, obtained from the analysis of RR interval series extracted from ten healthy subjects during stand-up tasks, suggest that the proposed entropy indices provide instantaneous tracking of the heartbeat complexity, also allowing for the definition of complexity variability indices. C1 [Valenza, Gaetano; Citi, Luca; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. RP Valenza, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM g.valenza@ieee.org; lciti@neurostat.mit.edu; e.scilingo@centropiaggio.unipi.it; barbieri@neurostat.mit.edu OI Barbieri, Riccardo/0000-0001-9381-3833; Valenza, Gaetano/0000-0001-6574-1879 NR 26 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-7929-0 J9 IEEE ENG MED BIO PY 2014 BP 6369 EP 6372 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044706089 ER PT S AU Valenza, G Orini, M Citi, L Minchole, A Pueyo, E Laguna, P Barbieri, R AF Valenza, G. Orini, M. Citi, L. Minchole, A. Pueyo, E. Laguna, P. Barbieri, R. GP IEEE TI Assessing Real-Time RR-QT Frequency-Domain Measures of Coupling and Causality through Inhomogeneous Point-Process Bivariate Models 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 ID HEART-RATE-VARIABILITY; INTERVAL VARIABILITY; ECG AB Ventricular repolarization instability is known to be related to arrhythmogenesis and increased risk of sudden cardiac death. These repolarization dynamics are linked to the distance between T-wave and Q-wave occurrances (QT) on the ECG, and they are coupled with R-wave to R-wave interval variability (RRV). Several efforts have been dedicated to the analysis of QT-RR interactions in order to provide both a quantification of the coupling and estimates of intrinsic repolarization dynamics. However, a methodology able to quantify dynamic changes in repolarization variability unrelated to RRV dynamics is still needed. In this study, we propose a bivariate model embedded within a multiple inhomogeneous point-process framework to obtain time-varying tracking of (causal) interactions between QT variability (QTV), a marker of repolarization variability, and RRV. Data from 15 healthy subjects undergoing a tilt table test were analyzed. Our results demonstrate that the model effectively captures the time-varying mutual QTV-RRV interactions. The analysis of time-varying coherence confirms that head-up tilt is associated with a decrease in linear QTV-RRV coupling, while time-varying directed coherence shows that intrinsic QTV becomes more prominent during head-up tilt. C1 [Valenza, G.; Barbieri, R.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Valenza, G (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM gvalenza@neurostat.mit.edu; barbieri@neurostat.mit.edu RI Orini, Michele/H-3937-2015; OI Orini, Michele/0000-0001-5773-0344; Barbieri, Riccardo/0000-0001-9381-3833; Valenza, Gaetano/0000-0001-6574-1879; laguna, Pablo/0000-0003-3434-9254 NR 20 TC 0 Z9 0 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 6475 EP 6478 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044706115 ER PT S AU Valenza, G Nardelli, M Bertschy, G Lanata, A Barbieri, R Scilingo, EP AF Valenza, Gaetano Nardelli, Mimma Bertschy, Gilles Lanata, Antonio Barbieri, Riccardo Scilingo, Enzo Pasquale GP IEEE TI Maximal-Radius Multiscale Entropy of Cardiovascular Variability: a Promising Biomarker of Pathological Mood States in Bipolar Disorders 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 ID HEART-RATE-VARIABILITY; THRESHOLD-VALUE-R; APPROXIMATE ENTROPY; MAJOR DEPRESSION; PREVALENCE; COMPLEXITY; BURDEN; MARKER AB Complexity measures from Multiscale Entropy (MSE) analysis of cardiovascular variability may provide potential biomarkers of pathological mental states such as major depression. To this extent, in this study we investigate whether complexity of Heart Rate Variability (HRV) is also affected in mental disorders such as bipolar disorders (BD). As part of the European project PSYCHE, eight BD patients experiencing multiple pathological mood states among depression, hypomania, and euthymia (i.e., good affective balance) underwent long-term night recordings through a comfortable sensing t-shirt with integrated fabric electrodes and sensors. Standard radius, i.e., 20% of the HRV standard deviation, and a maximal-radius choice for the sample entropy estimation were compared along with a further multiscale Renyi Entropy analysis. We found that, despite the inter-subject variability, the maximal-radius MSE analysis is able to discern the considered pathological mental states of BD. As the current clinical practice in diagnosing BD is only based on verbal interviews and scores from specific questionnaires, these findings provide evidence on the possibility of using heartbeat complexity as the basis of novel clinical biomarkers of mental disorders. C1 [Valenza, Gaetano; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02163 USA. RP Valenza, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02163 USA. EM g.valenza@ieee.org OI Barbieri, Riccardo/0000-0001-9381-3833; Lanata, Antonio/0000-0002-6540-5952; Valenza, Gaetano/0000-0001-6574-1879 NR 31 TC 3 Z9 3 U1 0 U2 0 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 6663 EP 6666 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044706159 ER PT S AU Valenza, G Citi, L Barbieri, R AF Valenza, Gaetano Citi, Luca Barbieri, Riccardo GP IEEE TI Assessment of Gait Nonlinear Dynamics by Inhomogeneous Point-Process Models 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 ID PARKINSONS-DISEASE; VARIABILITY; FLUCTUATIONS; FALLS AB Point-process linear models of stride intervals have been recently proven to provide a unique characterization of human gait dynamics through instantaneous time domain features. In this study we propose novel instantaneous measures characterizing nonlinear gait dynamics using a quadratic autoregressive inhomogeneous point-process model recently devised for the instantaneous assessment of physiological, natural, and physical discrete dynamical systems. Our mathematical framework accounts for long-term information given by the past events of non-stationary non-Gaussian time series, expressed by a Laguerre expansion of the Wiener-Volterra terms. Here, we present a study of gait variability from data gathered from physionet.org, including 15 recordings from young and elderly healthy volunteers, and patients with Parkinson's disease. Results show that our instantaneous polyspectral characterization provides an informative tracking of the inherent nonlinear dynamics of human gait, which is significantly affected by aging and locomotor disabilities. C1 [Valenza, Gaetano; Citi, Luca; Barbieri, Riccardo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Stat Res Lab, Boston, MA 02114 USA. [Valenza, Gaetano; Citi, Luca; Barbieri, Riccardo] MIT, Cambridge, MA 02139 USA. [Valenza, Gaetano] Univ Pisa, Res Ctr E Piaggio, Pisa, Italy. [Valenza, Gaetano] Univ Pisa, Dept Informat Engn, Pisa, Italy. [Citi, Luca] Univ Essex, Sch Comp Sci & Elect Engn, Colchester CO4 3SQ, Essex, England. RP Valenza, G (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM g.valenza@ieee.org; lciti@neurostat.mit.edu; barbieri@neurostat.mit.edu OI Barbieri, Riccardo/0000-0001-9381-3833; Valenza, Gaetano/0000-0001-6574-1879 NR 19 TC 0 Z9 0 U1 0 U2 0 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 6973 EP 6976 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BC1EL UT WOS:000350044706235 ER PT J AU Aizer, AA Chen, MH Hattangadi, J D'Amico, AV AF Aizer, Ayal A. Chen, Ming-Hui Hattangadi, Jona D'Amico, Anthony V. TI Initial management of prostate-specific antigen-detected, low-risk prostate cancer and the risk of death from prostate cancer SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; non-curative; active surveillance; prostatectomy; radiation; undergrading ID 12-CORE BIOPSY PROTOCOL; ACTIVE SURVEILLANCE; RADICAL PROSTATECTOMY; STRINGENT CRITERIA; IMPACT; TRIAL; RADIOTHERAPY; CANDIDATES; MORTALITY; NOMOGRAM AB Objective To evaluate whether older age in men with low-risk prostate cancer increases the risk of prostate cancer-specific mortality (PCSM) when non-curative approaches are selected as initial management. Patients and Methods The study cohort consisted of 27 969 men, with a median age of 67 years, with prostate-specific antigen (PSA)-detected, low-risk prostate cancer (clinical category T1c, Gleason score <= 6, and PSA <= 10) identified by the Surveillance, Epidemiology and End Results programme between 2004 and 2007. Fine and Gray's competing risk regression analysis was used to evaluate whether management with non-curative vs curative therapy was associated with an increased risk of PCSM after adjusting for PSA level, age at diagnosis and year of diagnosis. Results After a median follow-up of 2.75 years, 1121 men died, 60 (5.4%) from prostate cancer. Both older age (adjusted hazard ratio [AHR] 1.05; 95% confidence interval (CI) 1.02-1.08; P < 0.001) and non-curative treatment (AHR 3.34; 95% CI 1.97-5.67; P < 0.001) were significantly associated with an increased risk of PCSM. Men > the median age experienced increased estimates of PCSM when treated with non-curative as opposed to curative intent (P < 0.001); this finding was not seen in men <= the median age (P = 0.17). Conclusion Pending prospective validation, our study suggests that non-curative approaches for older men with 'low-risk' prostate cancer result in an increased risk of PCSM, suggesting the need for alternative approaches to exclude occult, high grade prostate cancer in these men. C1 [Aizer, Ayal A.; Hattangadi, Jona] Harvard Radiat Oncol Program, Boston, MA USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP Aizer, AA (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,Level L2,ASB1, Boston, MA 02115 USA. EM aaaizer@partners.org NR 33 TC 12 Z9 12 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD JAN PY 2014 VL 113 IS 1 BP 43 EP 50 DI 10.1111/j.1464-410X.2012.11789.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA CE7DB UT WOS:000351996200006 PM 23473327 ER PT J AU Mauri, T Coppadoro, A Bombino, M Bellani, G Zambelli, V Fornari, C Berra, L Bittner, EA Schmidt, U Sironi, M Bottazzi, B Brambilla, P Mantovani, A Pesenti, A AF Mauri, Tommaso Coppadoro, Andrea Bombino, Michela Bellani, Giacomo Zambelli, Vanessa Fornari, Carla Berra, Lorenzo Bittner, Edward A. Schmidt, Ulrich Sironi, Marina Bottazzi, Barbara Brambilla, Paolo Mantovani, Alberto Pesenti, Antonio TI Alveolar pentraxin 3 as an early marker of microbiologically confirmed pneumonia: a threshold-finding prospective observational study SO CRITICAL CARE LA English DT Article ID VENTILATOR-ASSOCIATED PNEUMONIA; BRONCHOALVEOLAR LAVAGE FLUID; CRITICALLY-ILL PATIENTS; LONG PENTRAXIN; PTX3; INFECTION; DIAGNOSIS; PROCALCITONIN; SEVERITY; DISEASE AB Introduction: Timely diagnosis of pneumonia in intubated critically ill patients is rather challenging. Pentraxin 3 (PTX3) is an acute-phase mediator produced by various cell types in the lungs. Animal studies have shown that, during pneumonia, PTX3 participates in fine-tuning of inflammation (for example, microbial clearance and recruitment of neutrophils). We previously described an association between alveolar PTX3 and lung infection in a small group of intubated patients. The aim of the present study was to determine a threshold level of alveolar PTX3 with elevated sensitivity and specificity for microbiologically confirmed pneumonia. Methods: We recruited 82 intubated patients from two intensive care units (San Gerardo Hospital, Monza, Italy, and Massachusetts General Hospital, Boston, MA, USA) undergoing bronchoalveolar lavage (BAL) as per clinical decision. We collected BAL fluid and plasma samples, together with relevant clinical and microbiological data. We assayed PTX3 and soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) in BAL fluid and PTX3, sTREM-1, C-reactive protein (CRP) and procalcitonin (PCT) in plasma. Two blinded independent physicians reviewed patient data to confirm pneumonia. We determined the PTX3 threshold in BAL fluid for pneumonia and compared it to other biomarkers. Results: Microbiologically confirmed pneumonia of bacterial (n = 12), viral (n = 4) or fungal (n = 8) etiology was diagnosed in 24 patients (29%). PTX3 levels in BAL fluid predicted pneumonia with an area under the receiving operator curve of 0.815 (95% CI = 0.710 to 0.921, P < 0.0001), whereas none of the other biomarkers were effective. In particular, PTX3 levels >= 1 ng/ml in BAL fluid predicted pneumonia in univariate analysis (beta = 2.784, SE = 0.792, P < 0.001) with elevated sensitivity (92%), specificity (60%) and negative predictive value (95%). Net reclassification index PTX3 values >= 1 ng/ml in BAL fluid for pneumonia indicated gain in sensitivity and/or specificity vs. all other mediators. These results did not change when we limited our analyses only to confirmed cases of bacterial pneumonia. Moreover, when we considered only the 70 patients who fulfilled the clinical criteria for the diagnosis of pneumonia at BAL fluid sampling, the diagnostic accuracy of PTX levels was confirmed in univariate and ROC curve analysis. Conclusions: In this hypothesis-generating convenience sample, a PTX3 level >= 1 ng/ml in BAL fluid was discriminative of microbiologically confirmed pneumonia in mechanically ventilated patients. C1 [Mauri, Tommaso; Coppadoro, Andrea; Bellani, Giacomo; Zambelli, Vanessa; Brambilla, Paolo; Pesenti, Antonio] Univ Milano Bicocca, Dept Hlth Sci, I-20900 Monza, Italy. [Mauri, Tommaso; Coppadoro, Andrea; Bombino, Michela; Bellani, Giacomo; Pesenti, Antonio] San Gerardo Hosp, Dept Emergency Med, I-20900 Monza, Italy. [Fornari, Carla] Univ Milano Bicocca, Dept Stat & Quantitat Methods, Res Ctr Publ Hlth, I-20900 Monza, Italy. [Berra, Lorenzo; Bittner, Edward A.; Schmidt, Ulrich] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Berra, Lorenzo; Bittner, Edward A.; Schmidt, Ulrich] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Sironi, Marina; Bottazzi, Barbara; Mantovani, Alberto] Humanitas Clin & Res Ctr, Dept Inflammat & Immunol, I-20089 Rozzano, MI, Italy. [Mantovani, Alberto] Univ Milan, Dept Translat Med, I-20122 Rozzano, MI, Italy. RP Pesenti, A (reprint author), Univ Milano Bicocca, Dept Hlth Sci, Via Cadore 48, I-20900 Monza, Italy. EM antonio.pesenti@unimib.it OI Bottazzi, Barbara/0000-0002-1930-9257 FU National Institutes of Health; University of Milan-Bicocca; Project HIIS, European Research Council; Italian Ministry of Health; Project Metadistretti-SEPSIS FX Sources of funding: institutional (TM, AC, MB, GB, VZ, CF, AP); training grant T32 from the National Institutes of Health (to LB); research grant FAR 2010 from the University of Milan-Bicocca (to PB); Project HIIS, European Research Council (to AM); a Ricerca Finalizzata grant from the Italian Ministry of Health (to AM); and Project Metadistretti-SEPSIS (to AM). The funding bodies did not have any role in the study design; the collection, analysis or interpretation of data; the writing of the manuscript; or the decision to submit the manuscript for publication. NR 35 TC 6 Z9 6 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2014 VL 18 IS 5 AR 562 DI 10.1186/s13054-014-0562-5 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA CE5DM UT WOS:000351850600077 PM 25314919 ER PT B AU Vaduganathan, M Lev, EI AF Vaduganathan, Muthiah Lev, Eli I. BE Waksman, R Gurbel, PA Gaglia, MA TI Aspirin Resistance SO ANTIPLATELET THERAPY IN CARDIOVASCULAR DISEASE LA English DT Article; Book Chapter ID CORONARY-ARTERY-DISEASE; RECURRENT CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; PLATELET-FUNCTION; ADENOSINE-DIPHOSPHATE; RETICULATED PLATELETS; ANTIPLATELET THERAPY; HEART-ASSOCIATION; METAANALYSIS; CLOPIDOGREL C1 [Vaduganathan, Muthiah] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02163 USA. [Lev, Eli I.] Rabin Med Ctr, Dept Cardiol, Med & Cardiol, Petah Tiqwa, Israel. [Lev, Eli I.] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. RP Vaduganathan, M (reprint author), Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02163 USA. NR 39 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, WEST SUSSEX PO19 8SQ, ENGLAND BN 978-1-118-49398-4; 978-1-118-27575-7 PY 2014 BP 277 EP 284 D2 10.1002/9781118493984 PG 8 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA BC3LE UT WOS:000351696100035 ER PT B AU Das, B AF Das, Bikul BE Rajasekhar, VK TI Altruistic Stem Cells and Cancer Stem Cells SO CANCER STEM CELLS LA English DT Article; Book Chapter ID SIDE POPULATION; OXIDATIVE STRESS; SOLID TUMORS; IDENTIFICATION; NICHE; NEUROBLASTOMA; PLURIPOTENCY; EXPRESSION; RESISTANCE; NETWORKS C1 [Das, Bikul] Stanford Univ, Stanford Inst Stem Cell Biol & Regenerat Med, Med Oncol, Stanford, CA 94305 USA. [Das, Bikul] Harvard Univ, Sch Dent Med, Forsyth Inst, Cambridge, MA 02138 USA. RP Das, B (reprint author), Stanford Univ, Stanford Inst Stem Cell Biol & Regenerat Med, Med Oncol, Stanford, CA 94305 USA. NR 53 TC 1 Z9 1 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-35620-3; 978-1-118-35616-6 PY 2014 BP 89 EP 105 D2 10.1002/9781118356203 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BC3IM UT WOS:000351670400009 ER PT S AU Tritos, NA Biller, BMK AF Tritos, Nicholas A. Biller, Beverly M. K. BE Fliers, E Korbonits, M Romijn, JA TI Cushing's disease SO CLINICAL NEUROENDOCRINOLOGY SE Handbook of Clinical Neurology LA English DT Article; Book Chapter ID CORTICOTROPIN-RELEASING HORMONE; DEXAMETHASONE-SUPPRESSION TEST; TERM-FOLLOW-UP; TRANSSPHENOIDAL SURGERY; DIFFERENTIAL-DIAGNOSIS; PITUITARY SURGERY; STIMULATION TEST; SALIVARY CORTISOL; DOPAMINE AGONISTS; NELSONS-SYNDROME C1 [Tritos, Nicholas A.; Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Tritos, Nicholas A.; Biller, Beverly M. K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Tritos, NA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Zero Emerson Pl,Suite 112, Boston, MA 02114 USA. EM ntritos@partners.org NR 121 TC 15 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0072-9752 BN 978-0-444-62612-7; 978-0-444-59602-4 J9 HAND CLINIC PY 2014 VL 124 BP 221 EP 234 PG 14 WC Endocrinology & Metabolism; Clinical Neurology SC Endocrinology & Metabolism; Neurosciences & Neurology GA BC1FG UT WOS:000350056900017 PM 25248590 ER PT S AU Pashtan, I Oh, KS Loeffler, JS AF Pashtan, Itai Oh, Kevin S. Loeffler, Jay S. BE Fliers, E Korbonits, M Romijn, JA TI Radiation therapy in the management of pituitary adenomas SO CLINICAL NEUROENDOCRINOLOGY SE Handbook of Clinical Neurology LA English DT Article; Book Chapter ID GAMMA-KNIFE RADIOSURGERY; LONG-TERM EFFICACY; STEREOTACTIC RADIOSURGERY; FOLLOW-UP; POSTOPERATIVE RADIOTHERAPY; TRANSSPHENOIDAL SURGERY; CUSHINGS-DISEASE; GROWTH-HORMONE; IRRADIATION; MACROADENOMAS C1 [Pashtan, Itai] Harvard Radiat Oncol Program, Boston, MA USA. [Oh, Kevin S.; Loeffler, Jay S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Loeffler, JS (reprint author), 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jloeffler@partners.org NR 52 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0072-9752 BN 978-0-444-62612-7; 978-0-444-59602-4 J9 HAND CLINIC PY 2014 VL 124 BP 317 EP 324 PG 8 WC Endocrinology & Metabolism; Clinical Neurology SC Endocrinology & Metabolism; Neurosciences & Neurology GA BC1FG UT WOS:000350056900023 PM 25248596 ER PT S AU Misra, M AF Misra, Madhusmita BE Fliers, E Korbonits, M Romijn, JA TI Neuroendocrine mechanisms in athletes SO CLINICAL NEUROENDOCRINOLOGY SE Handbook of Clinical Neurology LA English DT Article; Book Chapter ID BONE-MINERAL DENSITY; FUNCTIONAL HYPOTHALAMIC AMENORRHEA; GONADOTROPIN-RELEASING-HORMONE; PHYSIOLOGICAL ESTROGEN REPLACEMENT; LUTEAL-PHASE DEFICIENCY; ORAL-CONTRACEPTIVE USE; ANOREXIA-NERVOSA; ADOLESCENT GIRLS; LUTEINIZING-HORMONE; EXERCISING WOMEN C1 [Misra, Madhusmita] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. [Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457, Boston, MA 02114 USA. EM mmisra@partners.org FU NICHD NIH HHS [R01 HD060827, 1 R01HD060827-01A1, K24 HD071843]; NIDDK NIH HHS [P30 DK040561] NR 114 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0072-9752 BN 978-0-444-62612-7; 978-0-444-59602-4 J9 HAND CLINIC PY 2014 VL 124 BP 373 EP 386 PG 14 WC Endocrinology & Metabolism; Clinical Neurology SC Endocrinology & Metabolism; Neurosciences & Neurology GA BC1FG UT WOS:000350056900027 PM 25248600 ER PT J AU Schapira, MM Walker, CM Miller, T Fletcher, KE Ganschow, PS Jacobs, EA Imbert, D O'Connell, M Neuner, JM AF Schapira, Marilyn M. Walker, Cindy M. Miller, Tamara Fletcher, Kathlyn E. Ganschow, Pamela S. Jacobs, Elizabeth A. Imbert, Diana O'Connell, Maria Neuner, Joan M. TI Development and Validation of the Numeracy Understanding in Medicine Instrument Short Form SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID ITEM RESPONSE THEORY; FUNCTIONAL HEALTH LITERACY; RISK PERCEPTION; COMMUNICATION; INFORMATION; SCALE; CARE; COMPREHENSION; FRAMEWORK; ADULTS AB Health numeracy can be defined as the ability to understand and use numeric information and quantitative concepts in the context of health. The authors previously reported the development of the Numeracy Understanding in Medicine Instrument (NUMi), a 20-item test developed using item response theory. The authors now report the development and validation of a short form of the NUMi. Item statistics were used to identify a subset of 8 items representing a range of difficulty and content areas. Internal reliability was evaluated with Cronbach's alpha. Divergent and convergent validity was assessed by comparing scores of the S-NUMI with existing measures of education, print and numeric health literacy, mathematic achievement, cognitive reasoning, and the original NUMi. The 8-item scale had adequate reliability (alpha = .72) and was strongly correlated to the 20-item NUMi (alpha = .92). S-NUMi scores were strongly correlated with the Lipkus Expanded Health Numeracy Scale (alpha = .62), the Wide Range of Achievement Test-Mathematics (alpha = .72), and the Wonderlic Cognitive Ability Test (alpha = .76). Moderate correlation was found with education level (alpha = .58) and print literacy as measured by the Test of Functional Health Literacy in Adults (alpha = .49). Results show that the short form of the NUMi is a reliable and valid measure of health numeracy feasible for use in clinical and research settings. C1 [Schapira, Marilyn M.; Imbert, Diana] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Schapira, Marilyn M.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res Program, Philadelphia, PA USA. [Walker, Cindy M.; Miller, Tamara] Univ Wisconsin, Dept Educ Psychol, Milwaukee, WI 53201 USA. [Fletcher, Kathlyn E.; Neuner, Joan M.] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Fletcher, Kathlyn E.] Zablocki VA Med Ctr, Milwaukee, WI USA. [Ganschow, Pamela S.; O'Connell, Maria] Rush Univ, Sch Med, Dept Med, Chicago, IL 60612 USA. [Jacobs, Elizabeth A.] Univ Wisconsin, Sch Med, Dept Med, Madison, WI USA. RP Schapira, MM (reprint author), Univ Penn, Perelman Sch Med, Dept Med, 1110 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM mschap@upenn.edu FU National Cancer Institute of the National Institutes of Health [NC1R01CA115954]; American Cancer Society [121158-RSG-11-104-01-CPPB] FX This work was supported by grants from the National Cancer Institute of the National Institutes of Health NC1R01CA115954 and the American Cancer Society 121158-RSG-11-104-01-CPPB. NR 46 TC 4 Z9 4 U1 2 U2 3 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 240 EP 253 DI 10.1080/10810730.2014.933916 PG 14 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA CE5OI UT WOS:000351884600021 PM 25315596 ER PT J AU Giordano, S Darley-Usmar, V Zhang, JH AF Giordano, Samantha Darley-Usmar, Victor Zhang, Jianhua TI Autophagy as an essential cellular antioxidant pathway in neurodegenerative disease SO REDOX BIOLOGY LA English DT Article DE Parkinson's disease; Protein aggregation; Neurons; Mitochondrial dysfunction; Reactive oxygen species; Anti-oxidants; Autophagy; Toxins; Clinical trials; Animal models; Redox signaling ID EARLY PARKINSON-DISEASE; INCREASED OXIDATIVE DAMAGE; HUMAN SUBSTANTIA-NIGRA; ALPHA-SYNUCLEIN; DOPAMINERGIC-NEURONS; ALZHEIMERS-DISEASE; LIPID-PEROXIDATION; NITRIC-OXIDE; DOUBLE-BLIND; ENZYME-ACTIVITIES AB Oxidative stress including DNA damage, increased lipid and protein oxidation, are important features of aging and neurodegeneration suggesting that endogenous antioxidant protective pathways are inadequate or overwhelmed. Importantly, oxidative protein damage contributes to age-dependent accumulation of dysfunctional mitochondria or protein aggregates. In addition, environmental toxins such as rotenone and paraquat, which are risk factors for the pathogenesis of neurodegenerative diseases, also promote protein oxidation. The obvious approach of supplementing the primary antioxidant systems designed to suppress the initiation of oxidative stress has been tested in animal models and positive results were obtained. However, these findings have not been effectively translated to treating human patients, and clinical trials for antioxidant therapies using radical scavenging molecules such as alpha-tocopherol, ascorbate and coenzyme Q have met with limited success, highlighting several limitations to this approach. These could include: (1) radical scavenging antioxidants cannot reverse established damage to proteins and organelles; (2) radical scavenging antioxidants are oxidant specific, and can only be effective if the specific mechanism for neurodegeneration involves the reactive species to which they are targeted and (3) since reactive species play an important role in physiological signaling, suppression of endogenous oxidants maybe deleterious. Therefore, alternative approaches that can circumvent these limitations are needed. While not previously considered an antioxidant system we propose that the autophagy-lysosomal activities, may serve this essential function in neurodegenerative diseases by removing damaged or dysfunctional proteins and organelles. (C) 2014 The Authors. Published by Elsevier B.V. All rights reserved C1 [Giordano, Samantha; Darley-Usmar, Victor; Zhang, Jianhua] Univ Alabama Birmingham, Ctr Free Rad Biol, Birmingham, AL 35233 USA. [Giordano, Samantha; Darley-Usmar, Victor; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL USA. RP Zhang, JH (reprint author), Univ Alabama Birmingham, Ctr Free Rad Biol, Birmingham, AL 35233 USA. EM zhanja@uab.edu OI Zhang, Jianhua/0000-0002-2128-9574 FU VA merit award; [NIHR01-NS064090] FX This work was supported by NIHR01-NS064090 and a VA merit award (to JZ). NR 133 TC 69 Z9 73 U1 13 U2 50 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2317 J9 REDOX BIOL JI Redox Biol. PY 2014 VL 2 BP 82 EP 90 DI 10.1016/j.redox.2013.12.013 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CD0MY UT WOS:000350769600012 PM 24494187 ER PT S AU Daiger, SP Bowne, SJ Sullivan, LS Blanton, SH Weinstock, GM Koboldt, DC Fulton, RS Larsen, D Humphries, P Humphries, MM Pierce, EA Chen, R Li, YM AF Daiger, Stephen P. Bowne, Sara J. Sullivan, Lori S. Blanton, Susan H. Weinstock, George M. Koboldt, Daniel C. Fulton, Robert S. Larsen, David Humphries, Peter Humphries, Marian M. Pierce, Eric A. Chen, Rui Li, Yumei BE Ash, JD Grimm, C Hollyfield, JG Anderson, RE LaVail, MM Rickman, CB TI Application of Next-Generation Sequencing to Identify Genes and Mutations Causing Autosomal Dominant Retinitis Pigmentosa (adRP) SO RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 15th International Symposium on Retinal Degeneration (RD) CY JUL 16-21, 2012 CL GERMANY DE Retinitis pigmentosa; Next-generation sequencing; Linkage mapping; Mutation prevalence; Retinal gene capture; Whole-exome sequencing ID FAMILIES; PREVALENCE; ACCOUNT AB The goal of our research is to identify genes and mutations causing autosomal dominant retinitis pigmentosa (adRP). For this purpose we established a cohort of more than 250 independently ascertained families with adRP in the Houston Laboratory for Molecular Diagnosis of Inherited Eye Diseases. Affected members of each family were screened for disease-causing mutations in genes and gene regions that are commonly associated with adRP. By this approach, we detected mutations in 65% of the families, leaving 85 families that are likely to harbor mutations outside of the "common" regions or in novel genes. Of these, 32 families were tested by several types of next-generation sequencing (NGS), including (a) targeted polymerase chain reaction (PCR) NGS, (b) whole exome NGS, and (c) targeted retinal-capture NGS. We detected mutations in 11 of these families (31%) bringing the total detected in the adRP cohort to 70%. Several large families have also been tested for linkage using Afymetrix single nucleotide polymorphism (SNP) arrays. C1 [Daiger, Stephen P.; Bowne, Sara J.; Sullivan, Lori S.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA. [Blanton, Susan H.] Univ Miami, Miami Inst Human Genom, Miami, FL USA. [Weinstock, George M.; Koboldt, Daniel C.; Fulton, Robert S.; Larsen, David] Washington Univ, Sch Med, Genome Inst, St Louis, MO USA. [Humphries, Peter; Humphries, Marian M.] Univ Dublin Trinity Coll, Dept Genet, Dublin 2, Ireland. [Pierce, Eric A.] Massachusetts Eye & Ear Infirm, Ocular Genom Inst, Boston, MA 02114 USA. [Chen, Rui; Li, Yumei] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Daiger, SP (reprint author), Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, 1200 Herman Pressler Dr, Houston, TX 77030 USA. EM Stephen.P.Daiger@uth.tmc.edusss OI Pierce, Eric/0000-0002-2354-4102 FU NIH [EY007142]; Foundation Fighting Blindness FX This work was supported by NIH grant EY007142 and the Foundation Fighting Blindness. We thank Dr. David Birch, Dr John Heckenlively, Dr. Richard Lewis, Dr. Dianna Wheaton, Ms. Kari Branham, and Ms. Elizabeth Cadena for clinical assistance; and Ms. Cheryl Avery, Ms. Aimee Buhr, and Ms. Elizabeth Quimby for technical assistance. NR 13 TC 15 Z9 15 U1 2 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-3209-8; 978-1-4614-3208-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2014 VL 801 BP 123 EP 129 DI 10.1007/978-1-4614-3209-8_16 PG 7 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BC1TP UT WOS:000350418200017 PM 24664689 ER PT S AU Rohrer, B Kunchithapautham, K Genewsky, A Strauss, O AF Rohrer, Barbel Kunchithapautham, Kannan Genewsky, Andreas Strauss, Olaf BE Ash, JD Grimm, C Hollyfield, JG Anderson, RE LaVail, MM Rickman, CB TI Prolonged Src Kinase Activation, a Mechanism to Turn Transient, Sublytic Complement Activation into a Sustained Pathological Condition in Retinal Pigment Epithelium Cells SO RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 15th International Symposium on Retinal Degeneration (RD) CY JUL 16-21, 2012 CL GERMANY DE Complement activation; Vascular endothelial growth factor; Voltage-dependent calcium channel; Calcium imaging; Patch clamp analysis ID MACULAR DEGENERATION; VEGF; SECRETION; CA2+ AB Age-related macular degeneration (AMD) is a slowly progressing multifactorial disease involving genetic abnormalities and environmental insults. Genetic studies have demonstrated that polymorphisms in different complement proteins increase the risk for developing AMD. Previously, we have shown that in retinal pigment epithelium (RPE) monolayers, exposure to oxidative stress reduced complement inhibition on the cell surface, with the resulting increase in complement activation leading to vascular endothelial growth factor (VEGF) release and VEGF-receptor-2-mediated disruption of the monolayer barrier function. Complement activation was found to be sublytic and transient and require the assembly of the membrane attack complex (MAC). Here, we asked how this transient, sublytic complement activation could trigger long-term pathological changes in RPE cells. The initial activation of the L-type voltage-gated calcium channels was followed by calcium influx and activation of several kinases. While Erk/Ras activation was found to be transient, Src kinase phosphorylation was sustained. We have shown previously that Src kinase controls VEGF release from RPE cells by altering the activity of the L-type channel. We propose that the prolonged Src kinase activation, and its resulting effects on membrane depolarization and calcium influx, leads to sustained VEGF secretion. In addition, the previously shown effect of the autocrine positive feedback loop in RPE cells, involving VEGF-induced VEGF production and secretion via VEGFR-2 receptors, will augment and prolong the effects of sublytic complement activation. In summary, identification of the links between oxidative stress, chronic, low-grade activation of the complement system, and elevated VEGF expression and secretion might offer opportunities to selectively inhibit pathological VEGF release only. C1 [Rohrer, Barbel; Kunchithapautham, Kannan] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. [Rohrer, Barbel] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC 29401 USA. [Genewsky, Andreas; Strauss, Olaf] Klinikum Univ Regensburg, Dept Expt Ophthalmol, Regensburg, Germany. [Strauss, Olaf] Charite, Dept Ophthalmol, D-13353 Berlin, Germany. RP Rohrer, B (reprint author), Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave,SEI614, Charleston, SC 29425 USA. EM rohrer@musc.edu; kunchit@musc.edu; andreas_genewsky@mpipsykl.mpg.de; olaf.strauss@charite.de FU NEI NIH HHS [R01 EY019320, R01EY019320] NR 20 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-3209-8; 978-1-4614-3208-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2014 VL 801 BP 221 EP 227 DI 10.1007/978-1-4614-3209-8_29 PG 7 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BC1TP UT WOS:000350418200030 PM 24664702 ER PT S AU Woodell, A Rohrer, B AF Woodell, Alex Rohrer, Baerbel BE Ash, JD Grimm, C Hollyfield, JG Anderson, RE LaVail, MM Rickman, CB TI A Mechanistic Review of Cigarette Smoke and Age-Related Macular Degeneration SO RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 15th International Symposium on Retinal Degeneration (RD) CY JUL 16-21, 2012 CL GERMANY DE Cigarette smoke; Age-related macular degeneration; Oxidative stress; Antioxidant; Complement; Angiogenesis ID CAUSES OXIDATIVE DAMAGE; COMPLEMENT FACTOR-H; LIPID-PEROXIDATION; HUMAN RETINA; MOUSE MODEL; VITAMIN-C; PLASMA; ANGIOGENESIS; ASSOCIATIONS; PATHOGENESIS AB Age-related macular degeneration (AMD), a complex disease stemming from both genetic abnormalities and environmental insults, is the most common form of visual impairment in elderly individuals of the Western world. Many potential etiologies are linked to AMD, but smoking is the leading environmental insult associated with this maculopathy. Smoke-induced damage is mediated in part through direct oxidation, depletion of antioxidants, complement activation, and vascular transmutations. Clinically, these mechanisms manifest themselves as keystones of atrophic AMD: retinal pigment epithelium degeneration, formation of extracellular deposits such as drusen, and thickening of Bruch's membrane. Furthermore, smoking induces angiogenesis and choroidal neovascularization, advancing the course of the disease to late-stage AMD. Further exploration of the biological processes affected by cigarette smoke exposure will provide greater insight into the pathogenesis of AMD. C1 [Woodell, Alex; Rohrer, Baerbel] Med Univ S Carolina, Div Res, Dept Neurosci, Charleston, SC 29425 USA. [Rohrer, Baerbel] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. [Rohrer, Baerbel] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC 29401 USA. RP Rohrer, B (reprint author), Med Univ S Carolina, Div Res, Dept Neurosci, 167 Ashley Ave,SEI 614, Charleston, SC 29425 USA. EM woodell@musc.edu; rohrer@musc.edu FU National Institutes of Health (NIH) [R01EY019320]; Department of Veterans Affairs [I01 RX000444]; Foundation Fighting Blindness; Research to Prevent Blindness (RPB), Inc., New York, NY FX The authors thank Christine Curcio for critical discussions. This review was supported in part by the National Institutes of Health (NIH) (R01EY019320), Department of Veterans Affairs (I01 RX000444), Foundation Fighting Blindness, and an unrestricted grant to MUSC from Research to Prevent Blindness (RPB), Inc., New York, NY. The authors have no financial conflicts of interest. NR 38 TC 12 Z9 13 U1 1 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-3209-8; 978-1-4614-3208-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2014 VL 801 BP 301 EP 307 DI 10.1007/978-1-4614-3209-8_38 PG 7 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BC1TP UT WOS:000350418200039 PM 24664711 ER PT S AU Schnabolk, G Tomlinson, S Rohrer, B AF Schnabolk, Gloriane Tomlinson, Stephen Rohrer, Baerbel BE Ash, JD Grimm, C Hollyfield, JG Anderson, RE LaVail, MM Rickman, CB TI The Complement Regulatory Protein CD59: Insights into Attenuation of Choroidal Neovascularization SO RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 15th International Symposium on Retinal Degeneration (RD) CY JUL 16-21, 2012 CL GERMANY DE AMD; CD59; Complement; Choroidal neovascularization (CNV); Membrane attack complex (MAC) ID MACULAR DEGENERATION; MOUSE MODEL; INHIBITOR; ACTIVATION; DRUSEN; INJURY AB Complement activation is associated with age-related macular degeneration (AMD), with the retinal pigment epithelium (RPE) being one of the main target tissues. In AMD, disease severity is correlated with the formation of the membrane attack complex (MAC), the terminal step in the complement cascade, as well as diminished RPE expression of CD59, a membrane-bound regulatory protein of MAC formation. This has prompted the search for therapeutic strategies based on MAC inhibition, and soluble forms of CD59 (sCD59) have been investigated in mouse laser-induced choroidal neovascularization, a model for "wet" AMD. Unlike membrane-bound CD59, sCD59 provides relatively poor cell protection from complement, and different strategies to increase sCD59 activity at the cell membrane level have been investigated. These include increasing the circulatory half-life of sCD59 by the addition of an Fc moiety; increasing the half-life of sCD59 in target tissues by modifying CD59 with a (non-specific) membrane-targeting domain; and by locally overexpressing sCD59 via adenoviral vectors. Finally, a different strategy currently under investigation employs complement receptor (CR) 2-mediated targeting of CD59 exclusively to membranes under complement attack. CR2 recognizes long-lasting membrane-bound breakdown activation fragments of complement C3. CR2-CD59 may have greater therapeutic potential than other complement inhibitory approaches, since it can be administered either systemically or locally, it will bind specifically to membranes containing activated complement activation fragments, and dosing can be regulated. Hence, this strategy might offer opportunities for site-specific inhibition of complement in diseases with restricted sites of inflammation such as AMD. C1 [Tomlinson, Stephen; Rohrer, Baerbel] Ralph H Johnson VA Med Ctr, Div Res, Charleston, SC 29401 USA. [Tomlinson, Stephen] Med Univ S Carolina, Dept Microbiol, Charleston, SC 29425 USA. [Tomlinson, Stephen] Med Univ S Carolina, Dept Immunol, Charleston, SC 29425 USA. [Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. [Rohrer, Baerbel] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. RP Rohrer, B (reprint author), Ralph H Johnson VA Med Ctr, Div Res, Charleston, SC 29401 USA. EM faith@musc.edu; faith@musc.edu; rohrer@musc.edu FU National Institutes of Health (NIH) [R01EY019320]; Department of Veterans Affairs [I01 RX000444]; Foundation Fighting Blindness; Research to Prevent Blindness (RPB), Inc., New York, NY FX This review was supported in part by the National Institutes of Health (NIH) (R01EY019320), Department of Veterans Affairs (I01 RX000444), Foundation Fighting Blindness, and an unrestricted grant to MUSC from Research to Prevent Blindness (RPB), Inc., New York, NY. The authors have no financial conflicts of interest. NR 21 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-3209-8; 978-1-4614-3208-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2014 VL 801 BP 435 EP 440 DI 10.1007/978-1-4614-3209-8_55 PG 6 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BC1TP UT WOS:000350418200056 PM 24664728 ER PT S AU Pardue, MT Ciavatta, VT Hetling, JR AF Pardue, Machelle T. Ciavatta, Vincent T. Hetling, John R. BE Ash, JD Grimm, C Hollyfield, JG Anderson, RE LaVail, MM Rickman, CB TI Neuroprotective Effects of Low Level Electrical Stimulation Therapy on Retinal Degeneration SO RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 15th International Symposium on Retinal Degeneration (RD) CY JUL 16-21, 2012 CL GERMANY DE Retinal degeneration; Electrical stimulation; Subretinal; Transcorneal; Neuroprotection; Photoreceptors; Retinal ganglion cells ID MULLER CELLS; RETINITIS-PIGMENTOSA; RATS; PHOTORECEPTORS; INDUCTION; PROMOTES; SURVIVAL AB Low-level electrical stimulation applied to the eye has been shown to have neuroprotective effects on photoreceptors and retinal ganglion cells. In this review, we compare the effects of Subretinal Electrical Stimulation (SES), Transcorneal Electrical Stimulation (TES), and Whole Eye Stimulation (WES) on preserving retinal structure and function, and visual acuity, in retinal degeneration. Similarities and differences in stimulus parameters, targeted cells and growth factor expression will be discussed with emphasis on studies that have translated laboratory findings into clinical trials. C1 [Pardue, Machelle T.; Ciavatta, Vincent T.] Emory Univ, Sch Med, Ophthalmol, Atlanta, GA 30322 USA. [Pardue, Machelle T.; Ciavatta, Vincent T.] US Dept Vet Affairs, Rehab R&D Ctr Excellence, Decatur, GA USA. [Pardue, Machelle T.] Atlanta VA Med Ctr, Res Serv 151Oph, Decatur, GA 30033 USA. [Hetling, John R.] Univ Illinois, Bioengn, Chicago, IL USA. RP Pardue, MT (reprint author), Emory Univ, Sch Med, Ophthalmol, Atlanta, GA 30322 USA. EM mpardue@emory.edu; vciavat@emory.edu; JHetli1@uic.edu NR 29 TC 3 Z9 3 U1 0 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-3209-8; 978-1-4614-3208-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2014 VL 801 BP 845 EP 851 DI 10.1007/978-1-4614-3209-8_106 PG 7 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BC1TP UT WOS:000350418200107 PM 24664779 ER PT B AU Nikiforow, S Ritz, J AF Nikiforow, Sarah Ritz, Jerome BE Ballen, K TI Quantitative and Qualitative Immune Reconstitution Following Umbilical Cord Blood Transplantation SO UMBILICAL CORD BLOOD BANKING AND TRANSPLANTATION SE Stem Cell Biology and Regenerative Medicine LA English DT Article; Book Chapter ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; MOBILIZED PERIPHERAL-BLOOD; VERSUS-HOST-DISEASE; T REGULATORY CELLS; ADULT PATIENTS; ALLOGENEIC TRANSPLANTATION; DENDRITIC CELLS; ACUTE-LEUKEMIA; CD34(+) CELLS C1 [Nikiforow, Sarah; Ritz, Jerome] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Nikiforow, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave Dana168, Boston, MA 02215 USA. EM Sarah_Nikiforow@dfci.harvard.edu; Jerome_Ritz@dfci.harvard.edu NR 120 TC 0 Z9 0 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-3-319-06444-4; 978-3-319-06443-7 J9 STEM CELLS BIOL REG JI Stem Cell Biol. Regen. Med. PY 2014 BP 133 EP 152 DI 10.1007/978-3-319-06444-4_10 D2 10.1007/978-3-319-06444-4 PG 20 WC Cell & Tissue Engineering; Hematology; Transplantation SC Cell Biology; Hematology; Transplantation GA BC2CS UT WOS:000350755100011 ER PT B AU El-Jawahri, A Chen, YB AF El-Jawahri, Areej Chen, Yi-Bin BE Ballen, K TI Comparison of Umbilical Cord Blood to Adult Related and Unrelated Donors SO UMBILICAL CORD BLOOD BANKING AND TRANSPLANTATION SE Stem Cell Biology and Regenerative Medicine LA English DT Article; Book Chapter ID STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; MATCHED RELATED DONOR; NATURAL-KILLER-CELLS; HEMATOLOGIC MALIGNANCIES; RETROSPECTIVE ANALYSIS; MODULATES DIFFERENTIATION; CD34(+) CELLS C1 [El-Jawahri, Areej; Chen, Yi-Bin] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP El-Jawahri, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM Ychen6@partners.org NR 71 TC 0 Z9 0 U1 2 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-3-319-06444-4; 978-3-319-06443-7 J9 STEM CELLS BIOL REG JI Stem Cell Biol. Regen. Med. PY 2014 BP 235 EP 255 DI 10.1007/978-3-319-06444-4_18 D2 10.1007/978-3-319-06444-4 PG 21 WC Cell & Tissue Engineering; Hematology; Transplantation SC Cell Biology; Hematology; Transplantation GA BC2CS UT WOS:000350755100019 ER PT B AU Ballen, KK AF Ballen, Karen K. BE Ballen, K TI Selection of the Optimal Cord Blood Unit SO UMBILICAL CORD BLOOD BANKING AND TRANSPLANTATION SE Stem Cell Biology and Regenerative Medicine LA English DT Article; Book Chapter ID KIR-LIGAND INCOMPATIBILITY; ANTI-HLA ANTIBODIES; VERSUS-HOST DIRECTION; HEMATOLOGIC MALIGNANCY; ACUTE-LEUKEMIA; TRANSPLANTATION; OUTCOMES; IMPACT; RECIPIENTS; GRAFT C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Leukemia Program, Boston, MA 02163 USA. RP Ballen, KK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Leukemia Program, Boston, MA 02163 USA. EM kballen@partners.org NR 33 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 BN 978-3-319-06444-4; 978-3-319-06443-7 J9 STEM CELLS BIOL REG JI Stem Cell Biol. Regen. Med. PY 2014 BP 269 EP 275 DI 10.1007/978-3-319-06444-4_20 D2 10.1007/978-3-319-06444-4 PG 7 WC Cell & Tissue Engineering; Hematology; Transplantation SC Cell Biology; Hematology; Transplantation GA BC2CS UT WOS:000350755100021 ER PT J AU Shinohara, RT Sweeney, EM Goldsmith, J Shiee, N Mateen, FJ Calabresi, PA Jarso, S Pham, DL Reich, DS Crainiceanu, CM AF Shinohara, Russell T. Sweeney, Elizabeth M. Goldsmith, Jeff Shiee, Navid Mateen, Farrah J. Calabresi, Peter A. Jarso, Samson Pham, Dzung L. Reich, Daniel S. Crainiceanu, Ciprian M. CA Australian Imaging Biomarkers Life Alzheimers Dis Neuroimaging Initia TI Statistical normalization techniques for magnetic resonance imaging SO NEUROIMAGE-CLINICAL LA English DT Article DE Magnetic resonance imaging; Normalization; Statistics; Image analysis ID MULTIPLE-SCLEROSIS; INTENSITY STANDARDIZATION; ALZHEIMERS-DISEASE; MRI; BRAIN; SCALE; IMAGES AB While computed tomography and other imaging techniques are measured in absolute units with physical meaning, magnetic resonance images are expressed in arbitrary units that are difficult to interpret and differ between study visits and subjects. Much work in the image processing literature on intensity normalization has focused on histogram matching and other histogram mapping techniques, with little emphasis on normalizing images to have biologically interpretable units. Furthermore, there are no formalized principles or goals for the crucial comparability of image intensities within and across subjects. To address this, we propose a set of criteria necessary for the normalization of images. We further propose simple and robust biologically motivated normalization techniques for multisequence brain imaging that have the same interpretation across acquisitions and satisfy the proposed criteria. We compare the performance of different normalization methods in thousands of images of patients with Alzheimer's disease, hundreds of patients with multiple sclerosis, and hundreds of healthy subjects obtained in several different studies at dozens of imaging centers. (C) 2014 Published by Elsevier Inc. C1 [Shinohara, Russell T.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Sweeney, Elizabeth M.; Reich, Daniel S.] NINDS, Translat Neurol Unit, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Sweeney, Elizabeth M.; Reich, Daniel S.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. [Goldsmith, Jeff; Crainiceanu, Ciprian M.] Columbia Univ, Dept Biostat, New York, NY 10032 USA. [Shiee, Navid; Pham, Dzung L.] Henry M Jackson Fdn, Ctr Neurosci & Regenerat Med, Bethesda, MD 20892 USA. [Mateen, Farrah J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Mateen, Farrah J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Calabresi, Peter A.; Reich, Daniel S.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. [Jarso, Samson; Reich, Daniel S.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21287 USA. RP Shinohara, RT (reprint author), Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, 210 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rshi@upenn.edu RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 FU Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant) [U01 AG024904]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; Northern California Institute for Research and Education; NIH [P30 AG010129, K01 AG030514]; Intramural Research Program of the National Institute of Neurological Disorders and Stroke; National Institute of Neurological Disorders and Stroke [R01NS060910, R01NS085211]; National Institute of Biomedical Imaging and Bioengineering [R01EB012547]; Epidemiology and Biostatistics of Aging Training Grant from the National Institute on Aging [T32 AG000247] FX Data collection and sharing for this project were funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimers Association; Alzheimers Drug Discovery Foundation; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, Rev October 16, 2012 San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129 and K01 AG030514.; The authors thank Irene Cortese, Colin Shea, Roger Stone, the NINDS clinical group, and the NIMH/NINDS Functional Magnetic Resonance Imaging Facility technologists, who were instrumental in collecting and processing the data for this study. The research was partially supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke. The research of Shinohara and Crainiceanu was supported by Award Numbers R01NS060910 and R01NS085211 from the National Institute of Neurological Disorders and Stroke and Award Number R01EB012547 from the National Institute of Biomedical Imaging and Bioengineering. Shinohara was supported in part by the Epidemiology and Biostatistics of Aging Training Grant T32 AG000247 from the National Institute on Aging. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. NR 25 TC 16 Z9 16 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2014 VL 6 BP 9 EP 19 DI 10.1016/j.nicl.2014.08.008 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA CB5LL UT WOS:000349668500002 PM 25379412 ER PT J AU Yu, RJ Gollub, RL Spaeth, R Napadow, V Wasan, A Kong, J AF Yu, Rongjun Gollub, Randy L. Spaeth, Rosa Napadow, Vitaly Wasan, Ajay Kong, Jian TI Disrupted functional connectivity of the periaqueductal gray in chronic low back pain SO NEUROIMAGE-CLINICAL LA English DT Article DE Chronic low back pain; fMRI; Functional connectivity; Periaqueductal gray ID RESTING-STATE FMRI; ELECTRICAL-STIMULATION; PLACEBO ANALGESIA; SPONTANEOUS FLUCTUATIONS; GLOBUS-PALLIDUS; BRAIN; MODULATION; NETWORK; HUMANS; CORTEX AB Chronic low back pain is a common neurological disorder. The periaqueductal gray (PAG) plays a key role in the descending modulation of pain. In this study, we investigated brain resting state PAG functional connectivity (FC) differences between patients with chronic low back pain (cLBP) in low pain or high pain condition and matched healthy controls (HCs). PAG seed based functional connectivity (FC) analysis of the functional MR imaging data was performed to investigate the difference among the connectivity maps in the cLBP in the low or high pain condition and HC groups as well as within the cLBP at differing endogenous back pain intensities. Results showed that FC between the PAG and the ventral medial prefrontal cortex (vmPFC)/rostral anterior cingulate cortex (rACC) increased in cLBP patients compared to matched controls. In addition, we also found significant negative correlations between pain ratings and PAG-vmPFC/rACC FC in cLBP patients after pain-inducing maneuver. The duration of cLBP was negatively correlated with PAG-insula and PAG-amygdala FC before pain-inducing maneuver in the patient group. These findings are in line with the impairments of the descending pain modulation reported in patients with cLBP. Our results provide evidence showing that cLBP patients have abnormal FC in PAG centered pain modulation network during rest. (C) 2014 The Authors. Published by Elsevier Inc. C1 [Yu, Rongjun; Gollub, Randy L.; Spaeth, Rosa; Napadow, Vitaly; Wasan, Ajay; Kong, Jian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Yu, Rongjun; Gollub, Randy L.; Spaeth, Rosa; Napadow, Vitaly; Wasan, Ajay; Kong, Jian] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Yu, Rongjun] Natl Univ Singapore, Dept Psychol, Singapore 117548, Singapore. [Wasan, Ajay] Harvard Univ, Brigham & Womens Hosp, Med Sch HMS, Dept Anesthesiol, Boston, MA 02115 USA. RP Yu, RJ (reprint author), Dept Psychol, 9 Arts Link, Singapore 117570, Singapore. EM psyyr@nus.edu.sg OI Gollub, Randy L./0000-0002-9434-4044 FU NCCAM [R01AT006364, R01AT005280, PO1-AT002048]; National Center for Research Resources (NCRR) [M01-RR-01066, UL1 RR025758-01]; NCRR [P41RR14075] FX This work was supported by R01AT006364 (NCCAM) to Jian Kong, R01AT005280 (NCCAM) to Randy Gollub, PO1-AT002048 (NCCAM) to Bruce Rosen, M01-RR-01066 and UL1 RR025758-01 for Clinical Research Center Biomedical Imaging Core from National Center for Research Resources (NCRR), and P41RR14075 for Center for Functional Neuroimaging Technologies from NCRR. NR 85 TC 24 Z9 25 U1 1 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2014 VL 6 BP 100 EP 108 DI 10.1016/j.nicl.2014.08.019 PG 9 WC Neuroimaging SC Neurosciences & Neurology GA CB5LL UT WOS:000349668500012 PM 25379421 ER PT J AU Lampert, EJ Choudhury, KR Hostage, CA Rathakrishnan, B Weiner, M Petrella, JR Doraiswamy, PM AF Lampert, Erika J. Choudhury, Kingshuk Roy Hostage, Christopher A. Rathakrishnan, Bharath Weiner, Michael Petrella, Jeffrey R. Doraiswamy, P. Murali CA Alzheimers Dis Neuroimaging Initia TI Brain atrophy rates in first degree relatives at risk for Alzheimer's SO NEUROIMAGE-CLINICAL LA English DT Article DE Hippocampus; Amygdala; Entorhinal cortex; Memory; Dementia; Family history ID HUMAN CEREBRAL-CORTEX; MATERNAL HISTORY; APOLIPOPROTEIN-E; FAMILY-HISTORY; DISEASE; MRI; THICKNESS AB A positive family history (FH) raises the risk for late-onset Alzheimer's disease though, other than the known risk conferred by apolipoprotein epsilon 4 (ApoE4), much of the genetic variance remains unexplained. We examined the effect of family history on longitudinal regional brain atrophy rates in 184 subjects (42% FH+, mean age 79.9) with mild cognitive impairment (MCI) enrolled in a national biomarker study. An automated image analysis method was applied to T1-weightedMR images to measure atrophy rates for 20 cortical and subcortical regions. Mixed-effects linear regression models incorporating repeated-measures to control for within-subject variation over multiple time points tested the effect of FH over a follow-up of up to 48 months. Most of the 20 regions showed significant atrophy over time. Adjusting for age and gender, subjects with a positive FH had greater atrophy of the amygdala (p < 0.01), entorhinal cortex (p < 0.01), hippocampus (p < 0.053) and cortical gray matter (p < 0.009). However, when E4 genotype was added as a covariate, none of the FH+ effects remained significant. Analyses by ApoE genotype showed that the effect of FH on amygdala atrophy rates was numerically greater in epsilon 3 homozygotes than in E4 carriers, but this difference was not significant. FH+ subjects had numerically greater 4-year cognitive decline and conversion rates than FH- subjects but the difference was not statistically significant after adjusting for ApoE and other variables. We conclude that a positive family history of AD may influence cortical and temporal lobe atrophy in subjects with mild cognitive impairment, but it does not have a significant additional effect beyond the known effect of the E4 genotype. (C) 2014 The Authors. Published by Elsevier Inc. C1 [Lampert, Erika J.; Rathakrishnan, Bharath; Doraiswamy, P. Murali] Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. [Choudhury, Kingshuk Roy; Hostage, Christopher A.; Petrella, Jeffrey R.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. [Doraiswamy, P. Murali] Duke Univ, Med Ctr, Inst Brain Sci, Durham, NC 27710 USA. [Weiner, Michael] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Weiner, Michael] San Francisco VA Med Ctr, San Francisco, CA USA. [Weiner, Michael] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. RP Lampert, EJ (reprint author), Duke Univ, DUMC 3018 South Hosp, Durham, NC 27710 USA. EM ejlampert@gmail.com; kingshuk.roy.choudhury@duke.edu; cah1289@gmail.com; bg.rathakrishnan@gmail.com; Michael.weiner@ucsf.edu; jeffrey.petrella@duke.edu; murali.doraiswamy@duke.edu FU Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health grant) [U01 AG024904]; DOD ADNI (Department of Defense) [W81XWH-12-2-0012]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; Northern California Institute for Research and Education; ADNI; Wrenn Clinical Research Scholar award FX Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; BioClinica, Inc.; Biogen Idec Inc., Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & > Development LLC; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.; PMD and JRP have received research grants and/or advisory fees from several government agencies, advocacy groups and pharmaceutical/imaging companies. PMD received a grant from ADNI to support data collection for this study and he owns stock in Sonexa, Maxwell, Adverse Events and Clarimedix, whose products are not discussed here. EJL was supported by the Wrenn Clinical Research Scholar award. NR 21 TC 3 Z9 3 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2014 VL 6 BP 340 EP 346 DI 10.1016/j.nicl.2014.08.024 PG 7 WC Neuroimaging SC Neurosciences & Neurology GA CB5LL UT WOS:000349668500039 PM 25379448 ER PT J AU Rissling, AJ Miyakoshi, M Sugar, CA Braff, DL Makeig, S Light, GA AF Rissling, Anthony J. Miyakoshi, Makoto Sugar, Catherine A. Braff, David L. Makeig, Scott Light, Gregory A. TI Cortical substrates and functional correlates of auditory deviance processing deficits in schizophrenia SO NEUROIMAGE-CLINICAL LA English DT Article DE Schizophrenia; Mismatch negativity; Attention; EEG; Independent component analysis ID INDEPENDENT COMPONENT ANALYSIS; EVENT-RELATED POTENTIALS; INFERIOR FRONTAL GYRUS; DURATION MISMATCH NEGATIVITY; ANTERIOR CINGULATE CORTEX; SKILLS ASSESSMENT UPSA; WORKING-MEMORY; EEG DATA; 1ST-EPISODE SCHIZOPHRENIA; RESPONSE-INHIBITION AB Although sensory processing abnormalities contribute to widespread cognitive and psychosocial impairments in schizophrenia (SZ) patients, scalp-channel measures of averaged event-related potentials (ERPs) mix contributions from distinct cortical source-area generators, diluting the functional relevance of channel-based ERP measures. SZ patients (n = 42) and non-psychiatric comparison subjects (n = 47) participated in a passive auditory duration oddball paradigm, eliciting a triphasic (Deviant-Standard) tone ERP difference complex, here termed the auditory deviance response (ADR), comprised of a mid-frontal mismatch negativity (MMN), P3a positivity, and re-orienting negativity (RON) peak sequence. To identify its cortical sources and to assess possible relationships between their response contributions and clinical SZ measures, we applied independent component analysis to the continuous 68-channel EEG data and clustered the resulting independent components (ICs) across subjects on spectral, ERP, and topographic similarities. Six IC clusters centered in right superior temporal, right inferior frontal, ventral mid-cingulate, anterior cingulate, medial orbitofrontal, and dorsal mid-cingulate cortex each made triphasic response contributions. Although correlations between measures of SZ clinical, cognitive, and psychosocial functioning and standard (Fz) scalp-channel ADR peak measures were weak or absent, for at least four IC clusters one or more significant correlations emerged. In particular, differences in MMN peak amplitude in the right superior temporal IC cluster accounted for 48% of the variance in SZ-subject performance on tasks necessary for real-world functioning and medial orbitofrontal cluster P3a amplitude accounted for 40%/54% of SZ-subject variance in positive/negative symptoms. Thus, source-resolved auditory deviance response measures including MMN may be highly sensitive to SZ clinical, cognitive, and functional characteristics. Published by Elsevier Inc. C1 [Rissling, Anthony J.; Braff, David L.; Light, Gregory A.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Miyakoshi, Makoto; Makeig, Scott] Univ Calif San Diego, Inst Neural Computat, Swartz Ctr Computat Neurosci, La Jolla, CA 92093 USA. [Miyakoshi, Makoto] Japan Soc Promot Sci, Tokyo, Japan. [Braff, David L.; Light, Gregory A.] VA San Diego Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 22, Los Angeles, CA USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA USA. [Sugar, Catherine A.] Greater Los Angeles VA Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 22, Los Angeles, CA USA. RP Light, GA (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM glight@ucsd.edu FU National Alliance for Research on Schizophrenia and Depression/Brain and Behavior Research Foundation; Sydney R. Baer, Jr. Foundation; Department of Veteran Affairs (VISN 22 Mental Illness Research, Education, and Clinical Center); VeteransMedical Research Foundation; National Institute ofMental Health [MH079777, MH042228, MH065571, MH094151, MH093453, MH094320, UL1TR000100, MH081944]; Japan Society for the Promotion of Science (JSPS); Office of Naval Research; Swartz Foundation (Old Field, NY) FX This work was supported by the National Alliance for Research on Schizophrenia and Depression/Brain and Behavior Research Foundation, Sydney R. Baer, Jr. Foundation, the Department of Veteran Affairs (VISN 22 Mental Illness Research, Education, and Clinical Center), The VeteransMedical Research Foundation, The National Institute ofMental Health (MH079777, MH042228, MH065571, MH094151, MH093453, MH094320, UL1TR000100, MH081944), The Japan Society for the Promotion of Science (JSPS), The Office of Naval Research, and by a gift from The Swartz Foundation (Old Field, NY). The authors wish to thank Joyce Sprock, Marlena Pela, Richard Sharp, Stacy Langton, Arnaud Delorme, and Drs. Jared Young and Ricki-Lee Malaguti for their assistance, and (SM) Valerie Shafer, Peter Ullsperger, and Risto Naatanen for encouragement. NR 116 TC 13 Z9 13 U1 5 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2014 VL 6 BP 424 EP 437 DI 10.1016/j.nicl.2014.09.006 PG 14 WC Neuroimaging SC Neurosciences & Neurology GA CB5LL UT WOS:000349668500047 PM 25379456 ER PT S AU Liebscher, I Ackley, B Arac, D Ariestanti, DM Aust, G Bae, BI Bista, BR Bridges, JP Duman, JG Engel, FB Giera, S Goffinet, AM Hall, RA Hamann, J Hartmann, N Lin, HH Liu, MY Luo, R Mogha, A Monk, KR Peeters, MC Promel, S Ressl, S Schioth, HB Sigoillot, SM Song, HL Talbot, WS Tall, GG White, JP Wolfrum, U Xu, L Piao, XH AF Liebscher, Ines Ackley, Brian Arac, Demet Ariestanti, Donna M. Aust, Gabriela Bae, Byoung-il Bista, Bigyan R. Bridges, James P. Duman, Joseph G. Engel, Felix B. Giera, Stefanie Goffinet, Andre M. Hall, Randy A. Hamann, Jorg Hartmann, Nicole Lin, Hsi-Hsien Liu, Mingyao Luo, Rong Mogha, Amit Monk, Kelly R. Peeters, Miriam C. Proemel, Simone Ressl, Susanne Schioth, Helgi B. Sigoillot, Severine M. Song, Helen Talbot, William S. Tall, Gregory G. White, James P. Wolfrum, Uwe Xu, Lei Piao, Xianhua GP New York Acad Sci TI New functions and signaling mechanisms for the class of adhesion G protein-coupled receptors SO ANNALS REPORTS, VOL 1333 SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE adhesion G protein-coupled receptor; signal transduction; structural biology; development; myelination; synaptogenesis; cancer ID INTESTINAL EPITHELIAL-CELLS; ALPHA-LATROTOXIN; BIOCHEMICAL-CHARACTERIZATION; TISSUE TRANSGLUTAMINASE; DEPENDENT DEVELOPMENT; APOPTOTIC CELLS; MYOBLAST FUSION; SCHWANN-CELLS; GPR56; POLARITY AB The class of adhesion G protein-coupled receptors (aGPCRs), with 33 human homologs, is the second largest family of GPCRs. In addition to a seven-transmembrane alpha-helix-a structural feature of all GPCRs-the class of aGPCRs is characterized by the presence of a large N-terminal extracellular region. In addition, all aGPCRs but one (GPR123) contain a GPCR autoproteolysis-inducing (GAIN) domain that mediates autoproteolytic cleavage at the GPCR autoproteolysis site motif to generate N- and a C-terminal fragments (NTF and CTF, respectively) during protein maturation. Subsequently, the NTF and CTF are associated noncovalently as a heterodimer at the plasma membrane. While the biological function of the GAIN domain-mediated autocleavage is not fully understood, mounting evidence suggests that the NTF and CTF possess distinct biological activities in addition to their function as a receptor unit. We discuss recent advances in understanding the biological functions, signaling mechanisms, and disease associations of the aGPCRs. C1 [Liebscher, Ines; Proemel, Simone] Univ Leipzig, Inst Biochem, Fac Med, D-04109 Leipzig, Germany. [Ackley, Brian] Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA. [Arac, Demet] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. [Ariestanti, Donna M.] Tokyo Inst Technol, Dept Biol Sci, Yokohama, Kanagawa 227, Japan. [Aust, Gabriela] Univ Leipzig, Dept Surg, Res Labs, D-04109 Leipzig, Germany. [Bae, Byoung-il] Boston Childrens Hosp, Howard Hughes Med Inst, Div Genet & Genom, Boston, MA 02115 USA. [Bae, Byoung-il; Giera, Stefanie; Luo, Rong; Piao, Xianhua] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bista, Bigyan R.] MIT, Howard Hughes Med Inst, Koch Inst Integrat Canc Res, Cambridge, MA USA. [Bridges, James P.] Cincinnati Childrens Hosp Med Ctr, Div Pulm Biol, Perinatal Inst, Cincinnati, OH 45229 USA. [Duman, Joseph G.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. [Engel, Felix B.] Univ Erlangen Nurnberg, Dept Pathol, D-91054 Erlangen, Germany. [Giera, Stefanie; Luo, Rong; Piao, Xianhua] Boston Childrens Hosp, Div Newborn Med, Dept Med, Boston, MA 02115 USA. [Goffinet, Andre M.] Catholic Univ Louvain, Inst Neurosci, B-1200 Brussels, Belgium. [Hall, Randy A.] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. [Hamann, Jorg] Univ Amsterdam, Acad Med Ctr, Dept Expt Immunol, NL-1105 AZ Amsterdam, Netherlands. [Hartmann, Nicole] Univ Wurzburg, Inst Physiol, Dept Neurophysiol, Wurzburg, Germany. [Lin, Hsi-Hsien] Chang Gung Univ, Dept Microbiol & Immunol, Coll Med, Taoyuan, Taiwan. [Liu, Mingyao] E China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Shanghai 200062, Peoples R China. [Liu, Mingyao] E China Normal Univ, Sch Life Sci, Shanghai 200062, Peoples R China. [Mogha, Amit; Monk, Kelly R.] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO USA. [Peeters, Miriam C.] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Sect Metab Receptol & Enteroendocrinol, Copenhagen, Denmark. [Ressl, Susanne] Stanford Univ, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA. [Schioth, Helgi B.] Uppsala Univ, Dept Neurosci, Uppsala, Sweden. [Sigoillot, Severine M.] Coll France, CIRB, F-75231 Paris, France. [Song, Helen] Massachusetts Eye & Ear, Schepens Eye Res Inst, Boston, MA USA. [Talbot, William S.] Stanford Univ, Dept Dev Biol, Stanford, CA 94305 USA. [Tall, Gregory G.] Univ Rochester, Med Ctr, Dept Physiol & Pharmacol, Rochester, NY 14642 USA. [White, James P.] Harvard Univ, Sch Med, Dept Cell Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Wolfrum, Uwe] Johannes Gutenberg Univ Mainz, Inst Zool, Mainz, Germany. [Xu, Lei] Univ Rochester, Med Ctr, Dept Biomed Genet, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. [Xu, Lei] Univ Rochester, Dept Dermatol, Med Ctr, James P Wilmot Canc Ctr, Rochester, NY 14627 USA. RP Piao, XH (reprint author), Boston Childrens Hosp, Div Newborn Med, Dept Med, Boston, MA 02115 USA. EM xianhua.piao@childrens.harvard.edu RI Engel, Felix/A-1767-2008; OI Engel, Felix/0000-0003-2605-3429; Hall, Randy/0000-0002-8318-8728; Liebscher, Ines/0000-0003-4480-8987 FU NHGRI NIH HHS [T32 HG000044]; NIGMS NIH HHS [R01 GM098591]; NINDS NIH HHS [R01 NS072394, R01 NS057536] NR 99 TC 5 Z9 5 U1 4 U2 12 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 1333 BP 43 EP 64 DI 10.1111/nyas.12580 PG 22 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BC0WJ UT WOS:000349698600003 PM 25424900 ER PT S AU Frank, E Benabou, M Bentzley, B Bianchi, M Goldstein, T Konopka, G Maywood, E Pritchett, D Sheaves, B Thomas, J AF Frank, Ellen Benabou, Marion Bentzley, Brandon Bianchi, Matt Goldstein, Tina Konopka, Genevieve Maywood, Elizabeth Pritchett, David Sheaves, Bryony Thomas, Jessica GP New York Acad Sci TI Influencing circadian and sleep-wake regulation for prevention and intervention in mood and anxiety disorders: what makes a good homeostat? SO ANNALS REPORTS, VOL 1334 SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE homeostasis; circadian rhythms; psychiatry; genetics; mood disorders; anxiety disorder ID AUTISM SPECTRUM DISORDERS; SEASONAL AFFECTIVE-DISORDER; POSTTRAUMATIC STRESS-RESPONSE; MAJOR DEPRESSIVE DISORDER; RETINAL GANGLION-CELLS; GENE-EXPRESSION; SUPRACHIASMATIC NUCLEUS; LIGHT EXPOSURE; MORNINGNESS-EVENINGNESS; NEUROTROPHIC FACTOR AB All living organisms depend on homeostasis, the complex set of interacting metabolic chemical reactions for maintaining life and well-being. This is no less true for psychiatric well-being than for physical well-being. Indeed, a focus on homeostasis forces us to see how inextricably linked mental and physical well-being are. This paper focuses on these linkages. In particular, it addresses the ways in which understanding of disturbed homeostasis may aid in creating classes of patients with mood and anxiety disorders based on such phenotypes. At the cellular level, we may be able to compensate for the inability to study living brain tissue through the study of homeostatic mechanisms in fibroblasts, pluripotent human cells, and mitochondria and determine how homeostasis is disturbed at the level of these peripheral tissues through exogenous stress. We also emphasize the remarkable opportunities for enhancing knowledge in this area that are offered by advances in technology. The study of human behavior, especially when combined with our greatly improved capacity to study unique but isolated populations, offers particularly clear windows into the relationships among genetic, environmental, and behavioral contributions to homeostasis. C1 [Frank, Ellen; Goldstein, Tina] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. [Benabou, Marion] Inst Pasteur, Paris, France. [Bentzley, Brandon] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Bianchi, Matt] Harvard Univ, Sch Med, Dept Neurol, Sleep Div,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Konopka, Genevieve] Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA. [Maywood, Elizabeth] MRC Lab Mol Biol, Neurobiol Div, Cambridge, England. [Pritchett, David] Univ Oxford, John Radcliffe Hosp, Nuffield Lab Ophthalmol, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England. [Sheaves, Bryony] Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford, England. [Thomas, Jessica] Glostrup Univ Hosp, Mol Sleep Lab, Glostrup, Denmark. RP Frank, E (reprint author), Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. EM frankE@upmc.edu OI Bentzley, Brandon/0000-0001-6014-4514 FU Medical Research Council [MC_U105170643]; NIDA NIH HHS [R25 DA020537, F30 DA035065]; NIGMS NIH HHS [T32 GM008716]; Wellcome Trust [098461] NR 104 TC 3 Z9 3 U1 3 U2 7 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 1334 BP 1 EP 25 DI 10.1111/nyas.12600 PG 25 WC Primary Health Care; Multidisciplinary Sciences SC General & Internal Medicine; Science & Technology - Other Topics GA BC1EA UT WOS:000350025200001 PM 25532787 ER PT J AU Horan, WP Iacoboni, M Cross, KA Korb, A Lee, J Nori, P Quintana, J Wynn, JK Green, MF AF Horan, William P. Iacoboni, Marco Cross, Katy A. Korb, Alex Lee, Junghee Nori, Poorang Quintana, Javier Wynn, Jonathan K. Green, Michael F. TI Self-reported empathy and neural activity during action imitation and observation in schizophrenia SO NEUROIMAGE-CLINICAL LA English DT Article DE Imitation; Observation; Simulation; Schizophrenia; Mirror neuron system; Empathy ID PSYCHIATRIC RATING-SCALE; MIRROR-NEURON; SOCIAL COGNITION; FACIAL EXPRESSIONS; MOTOR CORTEX; MECHANISMS; EMOTIONS; SYSTEM; DYSFUNCTION; BRAIN AB Introduction: Although social cognitive impairments are key determinants of functional outcome in schizophrenia their neural bases are poorly understood. This study investigated neural activity during imitation and observation of finger movements and facial expressions in schizophrenia, and their correlates with self-reported empathy. Methods: 23 schizophrenia outpatients and 23 healthy controls were studied with functional magnetic resonance imaging (fMRI) while they imitated, executed, or simply observed finger movements and facial emotional expressions. Between-group activation differences, as well as relationships between activation and self-reported empathy, were evaluated. Results: Both patients and controls similarly activated neural systems previously associated with these tasks. We found no significant between-group differences in task-related activations. There were, however, between-group differences in the correlation between self-reported empathy and right inferior frontal (pars opercularis) activity during observation of facial emotional expressions. As in previous studies, controls demonstrated a positive association between brain activity and empathy scores. In contrast, the pattern in the patient group reflected a negative association between brain activity and empathy. Conclusions: Although patients with schizophrenia demonstrated largely normal patterns of neural activation across the finger movement and facial expression tasks, they reported decreased self perceived empathy and failed to show the typical relationship between neural activity and self-reported empathy seen in controls. These findings suggest that patients show a disjunction between automatic neural responses to low level social cues and higher level, integrative social cognitive processes involved in self-perceived empathy. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license. C1 [Horan, William P.; Lee, Junghee; Nori, Poorang; Quintana, Javier; Wynn, Jonathan K.; Green, Michael F.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Horan, William P.; Iacoboni, Marco; Cross, Katy A.; Korb, Alex; Lee, Junghee; Nori, Poorang; Quintana, Javier; Wynn, Jonathan K.; Green, Michael F.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Horan, WP (reprint author), Univ Calif Los Angeles, MIRECC 210A,Bldg 210,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM horan@ucla.edu RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU Abbott Laboratories; Amgen; Cypress; Lundbeck; Teva; Otsuka; Sunovion FX Dr. Green reports having received consulting fees from Abbott Laboratories, Amgen, Cypress, Lundbeck, and Teva. He has received speaking fees from Otsuka and Sunovion. The rest of the authors report no biomedical financial interests or potential conflicts of interest. NR 65 TC 7 Z9 8 U1 3 U2 19 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2014 VL 5 BP 100 EP 108 DI 10.1016/j.nicl.2014.06.006 PG 9 WC Neuroimaging SC Neurosciences & Neurology GA CB5LF UT WOS:000349667800013 PM 25009771 ER PT J AU Agam, Y Greenberg, JL Isom, M Falkenstein, MJ Jenike, E Wilhelm, S Manoach, DS AF Agam, Yigal Greenberg, Jennifer L. Isom, Marlisa Falkenstein, Martha J. Jenike, Eric Wilhelm, Sabine Manoach, Dara S. TI Aberrant error processing in relation to symptom severity in obsessive-compulsive disorder: A multimodal neuroimaging study SO NEUROIMAGE-CLINICAL LA English DT Article DE OCD; ERN; Anterior cingulate; Default network; Error processing; Multimodal neuroimaging ID ANTERIOR CINGULATE CORTEX; EVENT-RELATED FMRI; SURFACE-BASED ANALYSIS; MEDIAL FRONTAL-CORTEX; HUMAN CEREBRAL-CORTEX; BRAIN ACTIVITY; FUNCTIONAL-SIGNIFICANCE; RESPONSE-INHIBITION; STRIATAL CIRCUITS; ANTISACCADE TASK AB Background: Obsessive-compulsive disorder (OCD) is characterized by maladaptive repetitive behaviors that persist despite feedback. Using multimodal neuroimaging, we tested the hypothesis that this behavioral rigidity reflects impaired use of behavioral outcomes (here, errors) to adaptively adjust responses. We measured both neural responses to errors and adjustments in the subsequent trial to determine whether abnormalities correlate with symptom severity. Since error processing depends on communication between the anterior and the posterior cingulate cortex, we also examined the integrity of the cingulum bundle with diffusion tensor imaging. Methods: Participants performed the same antisaccade task during functional MRI and electroencephalography sessions. We measured error-related activation of the anterior cingulate cortex (ACC) and the error-related negativity (ERN). We also examined post-error adjustments, indexed by changes in activation of the default network in trials surrounding errors. Results: OCD patients showed intact error-related ACC activation and ERN, but abnormal adjustments in the post-vs. pre-error trial. Relative to controls, who responded to errors by deactivating the default network, OCD patients showed increased default network activation including in the rostral ACC (rACC). Greater rACC activation in the post-error trial correlated with more severe compulsions. Patients also showed increased fractional anisotropy (FA) in the white matter underlying rACC. Conclusions: Impaired use of behavioral outcomes to adaptively adjust neural responses may contribute to symptoms in OCD. The rACC locus of abnormal adjustment and relations with symptoms suggests difficulty suppressing emotional responses to aversive, unexpected events (e.g., errors). Increased structural connectivity of this paralimbic default network region may contribute to this impairment. (C) 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license C1 [Agam, Yigal; Greenberg, Jennifer L.; Isom, Marlisa; Falkenstein, Martha J.; Jenike, Eric; Wilhelm, Sabine; Manoach, Dara S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Agam, Yigal; Manoach, Dara S.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Manoach, DS (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 1-111, Charlestown, MA 02129 USA. EM dara@nmr.mgh.harvard.edu OI Falkenstein, Martha/0000-0001-5074-3409 FU National Institutes of Health [R01MH091078]; Oxford University Press; New Harbinger Publications; Guilford Publications; Forest Laboratories FX Dr. Wilhelm receives research funding from the National Institutes of Health (R01MH091078); royalties from Oxford University Press, New Harbinger Publications, and Guilford Publications; and support in the form of free medication and matching placebo from Forest Laboratories for a clinical trial funded by the National Institutes of Health; and has received speaking honoraria from various academic institutions. The other authors have no conflicts of interest to disclose. NR 99 TC 3 Z9 4 U1 4 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2014 VL 5 BP 141 EP 151 DI 10.1016/j.nicl.2014.06.002 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA CB5LF UT WOS:000349667800017 PM 25057466 ER PT J AU Meintjes, EM Narr, KL van der Kouwe, AJW Molteno, CD Pirnia, T Gutman, B Woods, RP Thompson, PM Jacobson, JL Jacobson, SW AF Meintjes, E. M. Narr, K. L. van der Kouwe, A. J. W. Molteno, C. D. Pirnia, T. Gutman, B. Woods, R. P. Thompson, P. M. Jacobson, J. L. Jacobson, S. W. TI A tensor-based morphometry analysis of regional differences in brain volume in relation to prenatal alcohol exposure SO NEUROIMAGE-CLINICAL LA English DT Article DE Tensor-based morphometry; Fetal alcohol spectrum disorders; Prenatal alcohol exposure; Structural MRI; Neurodevelopment; Morphology; Brain structure ID FALSE DISCOVERY RATES; FETAL ALCOHOL; SPECTRUM DISORDERS; MAGNETIC-RESONANCE; MATERNAL AGE; YOUNG-ADULTS; IN-UTERO; CHILDREN; PREGNANCY; DRINKING AB Reductions in brain volumes represent a neurobiological signature of fetal alcohol spectrum disorders (FASD). Less clear is how regional brain tissue reductions differ after normalizing for brain size differences linked with FASD and whether these profiles can predict the degree of prenatal exposure to alcohol. To examine associations of regional brain tissue excesses/deficits with degree of prenatal alcohol exposure and diagnosis with and without correction for overall brain volume, tensor-based morphometry (TBM) methods were applied to structural imaging data from a well-characterized, demographically homogeneous sample of children diagnosed with FASD (n = 39, 9.6-11.0 years) and controls (n = 16, 9.5-11.0 years). Degree of prenatal alcohol exposure was significantly associated with regionally pervasive brain tissue reductions in: (1) the thalamus, midbrain, and ventromedial frontal lobe, (2) the superior cerebellum and inferior occipital lobe, (3) the dorsolateral frontal cortex, and (4) the precuneus and superior parietal lobule. When overall brain size was factored out of the analysis on a subject-by-subject basis, no regions showed significant associations with alcohol exposure. FASD diagnosis was associated with a similar deformation pattern, but few of the regions survived FDR correction. In data-driven independent component analyses (ICA) regional brain tissue deformations successfully distinguished individuals based on extent of prenatal alcohol exposure and to a lesser degree, diagnosis. The greater sensitivity of the continuous measure of alcohol exposure compared with the categorical diagnosis across diverse brain regions underscores the dose dependence of these effects. The ICA results illustrate that profiles of brain tissue alterations may be a useful indicator of prenatal alcohol exposure when reliable historical data are not available and facial features are not apparent. (C) 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-SA license C1 [Meintjes, E. M.; Jacobson, J. L.; Jacobson, S. W.] Univ Cape Town, Fac Hlth Sci, Dept Human Biol, ZA-7925 Cape Town, South Africa. [Meintjes, E. M.] Univ Cape Town, Fac Hlth Sci, MRC UCT Med Imaging Res Unit, ZA-7925 Cape Town, South Africa. [Narr, K. L.; Pirnia, T.; Woods, R. P.] Univ Calif Los Angeles, Dept Neurol, Geffen Sch Med, Los Angeles, CA 90095 USA. [van der Kouwe, A. J. W.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [van der Kouwe, A. J. W.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Molteno, C. D.; Jacobson, J. L.; Jacobson, S. W.] Univ Cape Town, Fac Hlth Sci, Dept Psychiat & Mental Hlth, ZA-7925 Cape Town, South Africa. [Gutman, B.; Thompson, P. M.] Univ So Calif, Imaging Genet Ctr, Marina Del Rey, CA 90292 USA. [Jacobson, J. L.; Jacobson, S. W.] Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI 48201 USA. RP Meintjes, EM (reprint author), Univ Cape Town, Fac Hlth Sci, Dept Human Biol, Anzio Rd, ZA-7925 Cape Town, South Africa. EM ernesta.meintjes@gmail.com FU NIH [R01AA016781, R21AA017410, U01-AA014790]; South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa; Medical Research Council of South Africa; Fulbright South Africa Research/Scholar Award; Joseph Young Sr., Fund, State of Michigan; Ellison Medical Foundation FX This study was supported by NIH grants R01AA016781, R21AA017410, and U01-AA014790; South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa; Medical Research Council of South Africa; Fulbright South Africa Research/Scholar Award; Joseph Young Sr., Fund, State of Michigan; and Ellison Medical Foundation. We thank Bruce Spottiswoode, PhD, the CUBIC radiographers Marie-Louise de Villiers and Nailah Maroof, and our UCT and WSU research staff Nicolette Hamman, Mariska Pienaar, Maggie September, Emma Makin, Renee Sun, and Neil Dodge. We also thank the parents and children for their long-term participation in and contribution to the study. The authors declare no competing financial interests. NR 59 TC 14 Z9 14 U1 1 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2014 VL 5 BP 152 EP 160 DI 10.1016/j.nicl.2014.04.001 PG 9 WC Neuroimaging SC Neurosciences & Neurology GA CB5LF UT WOS:000349667800018 PM 25057467 ER PT J AU Mueller, SG Bateman, LM Laxer, KD AF Mueller, Susanne G. Bateman, Lisa M. Laxer, Kenneth D. TI Evidence for brainstem network disruption in temporal lobe epilepsy and sudden unexplained death in epilepsy SO NEUROIMAGE-CLINICAL LA English DT Article DE Deformation based morphometry; TLEgraph analysis; autonomic control; SUDEP ID SOLITARY TRACT NUCLEI; UNEXPECTED DEATH; CARDIOVASCULAR-RESPONSES; PERIAQUEDUCTAL GRAY; CUNEIFORM NUCLEUS; MESIAL SCLEROSIS; RAT; HYPOVENTILATION; MICROINJECTION; ABNORMALITIES AB The symptoms witnessed in unexplained death in epilepsy (SUDEP) suggest a breakdown of central autonomic control. Since the brainstem plays a crucial role in autonomic control, the objectives of this study were 1. To investigate if temporal lobe epilepsy (TLE) is associated with brainstem atrophy and to characterize it using graph Analysis 2. To compare the findings with those in two probable TLESUDEP. T1 images were obtained from 17 controls, 30 TLE (16 with mesial-temporal-sclerosis (TLE-MTS) and 14 without (TLE-no)) and from 2 patients who died of SUDEP. The brainstem was extracted, warped onto a brainstem atlas and Jacobian determinants maps (JDM) calculated. SPM8 was used to compare the JDMs at the group level, z-score maps were calculated for single subject analysis. Brainstem regions encompassing autonomic structures were identified based on macroscopic landmarks and mean z-scores from 5x5x5 voxel cubes extracted to calculate a new measure called atrophy-similarity index (ASI) for graph analysis. TLE-MTS had volume loss in the dorsal mesencephalon. The SUDEP cases had severe and more extensive volume loss in the same region. Nodal degrees and participation coefficients were decreased and local efficiency increased in SUDEP compared to controls. TLE is associated with volume loss in brainstem regions involved in autonomic control. Structural damage in these regions might increase the risk for a fatal dysregulation during situations with increased demand such as following severe seizures. (C) 2014 The Authors. Published by Elsevier Inc. C1 [Mueller, Susanne G.] VAMC, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. [Bateman, Lisa M.] Columbia Univ, Dept Neurol, New York, NY USA. [Laxer, Kenneth D.] Calif Pacific Med Ctr, Sutter Pacific Epilepsy Program, San Francisco, CA USA. RP Mueller, SG (reprint author), US Dept Vet Affairs, Med Ctr, Ctr Imaging Neurodegenerat Dis, Clement St 4150, San Francisco, CA 94121 USA. EM susanne.mueller@ucsf.edu FU NIH [RO1-NS31966] FX This work was supported by the NIH grant RO1-NS31966 to K.D.L. None of the authors has a conflict of interest to declare with regards to the findings reported in this manuscript. NR 37 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2014 VL 5 BP 208 EP 216 DI 10.1016/j.nicl.2014.06.010 PG 9 WC Neuroimaging SC Neurosciences & Neurology GA CB5LF UT WOS:000349667800024 PM 25068110 ER PT J AU Stoeckel, LE Garrison, KA Ghosh, SS Wighton, P Hanlon, CA Gilman, JM Greer, S Turk-Browne, NB Dedettencourt, MT Scheinost, D Craddock, C Thompson, T Calderon, V Bauer, CC George, M Breiter, HC Whitfield-Gabrieli, S Gabrieli, JD LaConte, SM Hirshberg, L Brewer, JA Hampson, M Van der Kouwe, A Mackey, S Evins, AE AF Stoeckel, L. E. Garrison, K. A. Ghosh, S. S. Wighton, P. Hanlon, C. A. Gilman, J. M. Greer, S. Turk-Browne, N. B. deDettencourt, M. T. Scheinost, D. Craddock, C. Thompson, T. Calderon, V. Bauer, C. C. George, M. Breiter, H. C. Whitfield-Gabrieli, S. Gabrieli, J. D. LaConte, S. M. Hirshberg, L. Brewer, J. A. Hampson, M. Van der Kouwe, A. Mackey, S. Evins, A. E. TI Optimizing real time fMRI neurofeedback for therapeutic discovery and development SO NEUROIMAGE-CLINICAL LA English DT Review DE Real time fMRI; Neurotherapeutic; Neurofeedback; Brain-computer interface ID CINGULATE CORTEX ACTIVITY; SELF-REGULATION; BRAIN ACTIVITY; FUNCTIONAL MRI; SELECTIVE ATTENTION; LEARNED REGULATION; EEG NEUROFEEDBACK; COGNITIVE CONTROL; MEMORY-SYSTEMS; MOTOR IMAGERY AB While reducing the burden of brain disorders remains a top priority of organizations like the World Health Organization and National Institutes of Health, the development of novel, safe and effective treatments for brain disorders has been slow. In this paper, we describe the state of the science for an emerging technology, real time functional magnetic resonance imaging (rtfMRI) neurofeedback, in clinical neurotherapeutics. We review the scientific potential of rtfMRI and outline research strategies to optimize the development and application of rtfMRI neurofeedback as a next generation therapeutic tool. We propose that rtfMRI can be used to address a broad range of clinical problems by improving our understanding of brain-behavior relationships in order to develop more specific and effective interventions for individuals with brain disorders. We focus on the use of rtfMRI neurofeedback as a clinical neurotherapeutic tool to drive plasticity in brain function, cognition, and behavior. Our overall goal is for rtfMRI to advance personalized assessment and intervention approaches to enhance resilience and reduce morbidity by correcting maladaptive patterns of brain function in those with brain disorders. (C) 2014 The Authors. Published by Elsevier Inc. C1 [Stoeckel, L. E.; Gilman, J. M.; Calderon, V.; Breiter, H. C.; Evins, A. E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Stoeckel, L. E.; Gilman, J. M.; Evins, A. E.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Stoeckel, L. E.; Wighton, P.; Gilman, J. M.; Van der Kouwe, A.] Athinoula A Martinos Ctr, Charlestown, MA USA. [Stoeckel, L. E.; Ghosh, S. S.; Thompson, T.; Whitfield-Gabrieli, S.; Gabrieli, J. D.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Garrison, K. A.; Brewer, J. A.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. [Wighton, P.; Van der Kouwe, A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hanlon, C. A.; George, M.] Med Univ S Carolina, Dept Psychiat, Charleston, SC USA. [Greer, S.] Univ Calif Berkeley, Dept Neurosci, Berkeley, CA 94720 USA. [Turk-Browne, N. B.] Princeton Univ, Dept Psychol, Princeton, NJ 08544 USA. [deDettencourt, M. T.] Princeton Univ, Princeton Neurosci Inst, Princeton, NJ 08544 USA. [Scheinost, D.; Hampson, M.] Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06520 USA. [Craddock, C.] Child Mind Inst, New York, NY USA. [Bauer, C. C.] Univ Nacl Autonoma Mexico, Inst Neurobiol, Mexico City 04510, DF, Mexico. [Breiter, H. C.] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Evanston, IL 60208 USA. [LaConte, S. M.] Virginia Tech, Sch Biomed Engn & Sci, Blacksburg, VA USA. [LaConte, S. M.] Virginia Tech, Carilion Res Inst, Blacksburg, VA USA. [Hirshberg, L.] Brown Univ, Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Brewer, J. A.] Univ Massachusetts, Sch Med, Dept Med & Psychiat, Amherst, MA 01003 USA. [Mackey, S.] Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA. RP Stoeckel, LE (reprint author), Massachusetts Gen Hosp, Ctr Addict Med, 60 Staniford St, Boston, MA 02114 USA. EM lstoeckel@mgh.harvard.edu RI Hampson, Michelle/K-6732-2015; OI Hampson, Michelle/0000-0003-3173-4210; Ghosh, Satrajit/0000-0002-5312-6729; Craddock, Cameron/0000-0002-4950-1303 FU Radcliffe Institute for Advanced Study; National Institutes of Health [K23DA032612, K24DA030443, R21DA030523, R21/33DA026104, K01 DA034093, K24DA029262, R01 AT007922-01, R03 DA029163-01A1, K12 DA00167, P50 DA09241, R01 AA02152901A1, R01 MH095789, 5R21DA026085]; Norman E. Zinberg Fellowship in Addiction Psychiatry at Harvard Medical School; Poitras Center for Affective Disorders Research; Charles A. King Trust; McGovern Institute Neurotechnology Program; Massachusetts General Hospital Department of Psychiatry; Biomedical Technology Program of the NIH National Center for Research Resources (NCRR) FX The ideas for this paper were developed at a workshop in July 2013 supported by the Radcliffe Institute for Advanced Study. Support was also provided in part by the National Institutes of Health: K23DA032612 (LES); K24DA030443 (AEE); R21DA030523 (AEE, JDG); R21/33DA026104 (HCB, AK); K01 DA034093 (JMG), K24DA029262 (SM), R01 AT007922-01 (JAB), R03 DA029163-01A1 (JAB), K12 DA00167 (JAB), P50 DA09241 (JAB), R01 AA02152901A1 (SML), R01 MH095789 (MH), 5R21DA026085 (MG), the Norman E. Zinberg Fellowship in Addiction Psychiatry at Harvard Medical School (LES, JMG), philanthropic donations from the Poitras Center for Affective Disorders Research (SWG), the Charles A. King Trust (LES), the McGovern Institute Neurotechnology Program (SG, JDG, AEE), and private funds to the Massachusetts General Hospital Department of Psychiatry (AEE). Research presented in this paper was also carried out in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41RR14075, a P41 Regional Resource supported by the Biomedical Technology Program of the NIH National Center for Research Resources (NCRR). NR 117 TC 38 Z9 38 U1 7 U2 27 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2014 VL 5 BP 245 EP 255 DI 10.1016/j.nicl.2014.07.002 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA CB5LF UT WOS:000349667800028 PM 25161891 ER PT J AU Damaraju, E Allen, EA Belger, A Ford, JM McEwen, S Mathalon, DH Mueller, BA Pearlson, GD Potkin, SG Preda, A Turner, JA Vaidya, JG van Erp, TG Calhoun, VD AF Damaraju, E. Allen, E. A. Belger, A. Ford, J. M. McEwen, S. Mathalon, D. H. Mueller, B. A. Pearlson, G. D. Potkin, S. G. Preda, A. Turner, J. A. Vaidya, J. G. van Erp, T. G. Calhoun, V. D. TI Dynamic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia SO NEUROIMAGE-CLINICAL LA English DT Article ID EYE-MOVEMENT SLEEP; RESTING-STATE; BRAIN ACTIVITY; GRAPHICAL LASSO; NETWORK; FLUCTUATIONS; CONNECTOMICS; FMRI; DYSFUNCTION; REGRESSION AB Schizophrenia is a psychotic disorder characterized by functional dysconnectivity or abnormal integration between distant brain regions. Recent functional imaging studies have implicated large-scale thalamo-cortical connectivity as being disrupted in patients. However, observed connectivity differences in schizophrenia have been inconsistent between studies, with reports of hyperconnectivity and hypoconnectivity between the same brain regions. Using resting state eyes-closed functional imaging and independent component analysis on a multi-site data that included 151 schizophrenia patients and 163 age- and gender matched healthy controls, we decomposed the functional brain data into 100 components and identified 47 as functionally relevant intrinsic connectivity networks. We subsequently evaluated group differences in functional network connectivity, both in a static sense, computed as the pairwise Pearson correlations between the full network time courses (5.4 minutes in length), and a dynamic sense, computed using sliding windows (44 s in length) and k-means clustering to characterize five discrete functional connectivity states. Static connectivity analysis revealed that compared to healthy controls, patients show significantly stronger connectivity, i.e., hyperconnectivity, between the thalamus and sensory networks (auditory, motor and visual), as well as reduced connectivity (hypoconnectivity) between sensory networks from all modalities. Dynamic analysis suggests that (1), on average, schizophrenia patients spend much less time than healthy controls in states typified by strong, large-scale connectivity, and (2), that abnormal connectivity patterns are more pronounced during these connectivity states. In particular, states exhibiting cortical-subcortical antagonism (anti-correlations) and strong positive connectivity between sensory networks are those that show the group differences of thalamic hyperconnectivity and sensory hypoconnectivity. Group differences are weak or absent during other connectivity states. Dynamic analysis also revealed hypoconnectivity between the putamen and sensory networks during the same states of thalamic hyperconnectivity; notably, this finding cannot be observed in the static connectivity analysis. Finally, in post-hoc analyses we observed that the relationships between sub-cortical low frequency power and connectivity with sensory networks is altered in patients, suggesting different functional interactions between sub-cortical nuclei and sensorimotor cortex during specific connectivity states. While important differences between patients with schizophrenia and healthy controls have been identified, one should interpret the results with caution given the history of medication in patients. Taken together, our results support and expand current knowledge regarding dysconnectivity in schizophrenia, and strongly advocate the use of dynamic analyses to better account for and understand functional connectivity differences. (C) 2014 The Authors. Published by Elsevier Inc. C1 [Damaraju, E.; Allen, E. A.; Calhoun, V. D.] Mind Res Network, Albuquerque, NM USA. [Allen, E. A.] Univ Bergen, KG Jebsen Ctr Res Neuropsychiat Disorders, Bergen, Norway. [Belger, A.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Ford, J. M.; Mathalon, D. H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Ford, J. M.; Mathalon, D. H.] San Francisco VA Med Ctr, San Francisco, CA USA. [McEwen, S.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA USA. [Mueller, B. A.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Pearlson, G. D.] Yale Univ, Sch Med, New Haven, CT USA. [Potkin, S. G.; Preda, A.; van Erp, T. G.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [Turner, J. A.] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. [Vaidya, J. G.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Calhoun, V. D.] Univ New Mexico, Dept ECE, Albuquerque, NM 87131 USA. RP Damaraju, E (reprint author), 1101 Yale Blvd NE, Albuquerque, NM 87106 USA. EM edamaraju@mrn.org RI Preda, Adrian /K-8889-2013; OI Preda, Adrian /0000-0003-3373-2438; Potkin, Steven/0000-0003-1028-1013; Belger, Aysenil/0000-0003-2687-1966 FU NCRR NIH HHS [U24 RR021992]; NICHD NIH HHS [U54 HD079124]; NIGMS NIH HHS [P20 GM103472]; NIMH NIH HHS [K01 MH099431] NR 54 TC 70 Z9 72 U1 3 U2 18 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2014 VL 5 BP 298 EP 308 DI 10.1016/j.nicl.2014.07.003 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA CB5LF UT WOS:000349667800033 PM 25161896 ER PT J AU Verly, M Verhoeven, J Zink, I Mantini, D Peeters, R Deprez, S Emsell, L Boets, B Noens, I Steyaert, J Lagae, L De Cock, P Rommel, N Sunaert, S AF Verly, Marjolein Verhoeven, Judith Zink, Inge Mantini, Dante Peeters, Ronald Deprez, Sabine Emsell, Louise Boets, Bart Noens, Ilse Steyaert, Jean Lagae, Lieven De Cock, Paul Rommel, Nathalie Sunaert, Stefan TI Altered functional connectivity of the language network in ASD: Role of classical language areas and cerebellum SO NEUROIMAGE-CLINICAL LA English DT Article DE Autism spectrum disorders; Cerebellum; Language function; Resting state fMRI ID AUTISM SPECTRUM DISORDERS; INFANTILE-AUTISM; SENTENCE COMPREHENSION; PREFRONTAL CORTEX; BRAIN-DEVELOPMENT; VERB GENERATION; CROSSING FIBERS; WHITE-MATTER; MOTOR TASK; IMPAIRMENT AB The development of language, social interaction and communicative skills is remarkably different in the child with autism spectrum disorder (ASD). Atypical brain connectivity has frequently been reported in this patient population. However, the neural correlates underlying their disrupted language development and functioning are still poorly understood. Using resting state fMRI, we investigated the functional connectivity properties of the language network in a group of ASD patients with clear comorbid language impairment (ASD-LI; N = 19) and compared them to the language related connectivity properties of 23 age-matched typically developing children. A verb generation task was used to determine language components commonly active in both groups. Eight joint language components were identified and subsequently used as seeds in a resting state analysis. Interestingly, both the interregional and the seed-based whole brain connectivity analysis showed preserved connectivity between the classical intrahemispheric language centers, Wernicke's and Broca's areas. In contrast however, a marked loss of functional connectivity was found between the right cerebellar region and the supratentorial regulatory language areas. Also, the connectivity between the interhemispheric Broca regions and modulatory control dorsolateral prefrontal region was found to be decreased. This disruption of normal modulatory control and automation function by the cerebellum may underlie the abnormal language function in children with ASD-LI. (C) 2014 The Authors. Published by Elsevier Inc. C1 [Verly, Marjolein; Zink, Inge; Rommel, Nathalie] Katholieke Univ Leuven, Dept Neurosci Exp ORL, Leuven, Belgium. [Verly, Marjolein; Verhoeven, Judith; Peeters, Ronald; Deprez, Sabine; Emsell, Louise; Sunaert, Stefan] Katholieke Univ Leuven, Univ Hosp, Dept Radiol, Leuven, Belgium. [Verhoeven, Judith; Boets, Bart; Noens, Ilse; Steyaert, Jean; De Cock, Paul; Sunaert, Stefan] Katholieke Univ Leuven, Leuven Autism Res LAURES Consortium, Leuven, Belgium. [Verhoeven, Judith; Lagae, Lieven; De Cock, Paul] Katholieke Univ Leuven, Univ Hosp, Dept Pediat, Leuven, Belgium. [Mantini, Dante] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. [Zink, Inge] ETH, Dept Heath Sci & Technol, CH-8057 Zurich, Switzerland. [Mantini, Dante] Katholieke Univ Leuven, Dept Neurosci, Lab Neuro & Psychophysiol, B-3000 Leuven, Belgium. [Boets, Bart; Noens, Ilse] Katholieke Univ Leuven, Parenting & Special Educ Res Unit, Leuven, Belgium. [Boets, Bart; Steyaert, Jean] Katholieke Univ Leuven, Univ Hosp, Dept Child & Adolescent Psychiat, Leuven, Belgium. [Noens, Ilse] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Steyaert, Jean] Maastricht Univ, Dept Clin Genet, NL-6200 MD Maastricht, Netherlands. [De Cock, Paul] Katholieke Univ Leuven, Univ Hosp, Ctr Dev Disabil, Leuven, Belgium. RP Verly, M (reprint author), Katholieke Univ Leuven, Dept Neurosci Expt Otorinolaryngol, Herestr 49, B-3000 Leuven, Belgium. EM marjolein.verly@med.kuleuven.be RI Mantini, Dante/D-6989-2014; deprez, sabine/N-8390-2016; OI Mantini, Dante/0000-0001-6485-5559; deprez, sabine/0000-0001-7451-5355; Emsell, Louise/0000-0003-0011-4158 FU Fund for Scientific Research-Flanders (F.W.O.) [G.0354.06]; Belgian Inter University Attraction Pole [6/29]; KU Leuven Research Council [IDO/08/013] FX The authors are grateful to our participants and healthy volunteers who made this research possible. This study was supported by the Fund for Scientific Research-Flanders (F.W.O.) (research grant G.0354.06, doctoral mandate to JSV, post-doctoral mandate to DM and BB), by the Belgian Inter University Attraction Pole (grant 6/29) and by the KU Leuven Research Council (grant IDO/08/013). NR 83 TC 24 Z9 25 U1 9 U2 24 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2014 VL 4 BP 374 EP 382 DI 10.1016/j.nicl.2014.01.008 PG 9 WC Neuroimaging SC Neurosciences & Neurology GA CB5LD UT WOS:000349667600040 PM 24567909 ER PT J AU Adluru, N Destiche, DJ Lu, SYF Doran, ST Birdsill, AC Melah, KE Okonkwo, OC Alexander, AL Dowling, NM Johnson, SC Sager, MA Bendlin, BB AF Adluru, Nagesh Destiche, Daniel J. Lu, Sharon Yuan-Fu Doran, Samuel T. Birdsill, Alex C. Melah, Kelsey E. Okonkwo, Ozioma C. Alexander, Andrew L. Dowling, N. Maritza Johnson, Sterling C. Sager, Mark A. Bendlin, Barbara B. TI White matter microstructure in late middle-age: Effects of apolipoprotein E4 and parental family history of Alzheimer's disease SO NEUROIMAGE-CLINICAL LA English DT Article DE Alzheimer's disease; family history; APOE4; diffusion tensor imaging; MRI; risk factors; age sex ID MILD-COGNITIVE-IMPAIRMENT; DIFFUSION TENSOR TRACTOGRAPHY; APOE EPSILON-4 ALLELE; POSITRON-EMISSION-TOMOGRAPHY; CORPUS-CALLOSUM ATROPHY; VOXEL-BASED MORPHOMETRY; DETECTS AXONAL INJURY; IN-VIVO; GRAY-MATTER; RHESUS-MONKEY AB Introduction: Little is still known about the effects of risk factors for Alzheimer's disease (AD) on white matter microstructure in cognitively healthy adults. The purpose of this cross-sectional study was to assess the effect of two well-known risk factors for AD, parental family history and APOE4 genotype. Methods: This study included 343 participants from the Wisconsin Registry for Alzheimer's Prevention, who underwent diffusion tensor imaging (DTI). A region of interest analysis was performed on fractional anisotropy maps, in addition to mean, radial, and axial diffusivity maps, aligned to a common template space using a diffeomorphic, tensor-based registration method. The analysis focused on brain regions known to be affected in AD including the corpus callosum, superior longitudinal fasciculus, fornix, cingulum, and uncinate fasciculus. Analyses assessed the impact of APOE4, parental family history of AD, age, and sex on white matter microstructure in late middle-aged participants (aged 47-76 years). Results: Both APOE4 and parental family history were associated with microstructural white matter differences. Participants with parental family history of AD had higher FA in the genu of the corpus callosum and the superior longitudinal fasciculus. We observed an interaction between family history and APOE4, where participants who were family history positive but APOE4 negative had lower axial diffusivity in the uncinate fasciculus, and participants who were both family history positive and APOE4 positive had higher axial diffusivity in this region. We also observed an interaction between APOE4 and age, whereby older participants (>= 65 years of age) who were APOE4 carriers, had higher MD in the superior longitudinal fasciculus and in the portion of the cingulum bundle running adjacent to the cingulate cortex, compared to non-carriers. Older participants who were APOE4 carriers also showed higher radial diffusivity in the genu compared to non-carriers. Across all participants, age had an effect on FA, MD, and axial and radial diffusivities. Sex differences were observed in FA and radial diffusivity. Conclusion: APOE4 genotype, parental family history of AD, age, and sex are all associated with microstructural white matter differences in late middle-aged adults. In participants at risk for AD, alterations in diffusion characteristics-both expected and unexpected-may represent cellular changes occurring at the earliest disease stages, but further work is needed. Higher mean, radial, and axial diffusivities were observed in participants who are more likely to be experiencing later stage preclinical pathology, including participants who were both older and carried APOE4, or who were positive for both APOE4 and parental family history of AD. (C) 2014 The Authors. Published by Elsevier Inc. C1 [Adluru, Nagesh; Destiche, Daniel J.; Lu, Sharon Yuan-Fu; Doran, Samuel T.; Alexander, Andrew L.] Waisman Lab Brain Imaging & Behav, Madison, WI USA. [Birdsill, Alex C.; Melah, Kelsey E.; Okonkwo, Ozioma C.; Dowling, N. Maritza; Johnson, Sterling C.; Sager, Mark A.; Bendlin, Barbara B.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Dis Res Ctr, Dept Med, Madison, WI 53792 USA. [Alexander, Andrew L.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med Phys, Madison, WI 53705 USA. [Alexander, Andrew L.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Psychiat, Madison, WI 53719 USA. [Dowling, N. Maritza] Dept Biostat & Med Informat, Madison, WI 53792 USA. [Johnson, Sterling C.; Sager, Mark A.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA. [Johnson, Sterling C.; Sager, Mark A.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Inst, Madison, WI 53719 USA. RP Bendlin, BB (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Dis Res Ctr, J5-1 Mezzanine,600 Highland Ave, Madison, WI 53792 USA. EM bbb@medicine.wisc.edu OI Bendlin, Barbara/0000-0002-0580-9875 FU Alzheimer's Association [NIRG-09-132626]; National Institute on Aging [R01 AG037639, R01 AG027161]; ADRC [P50 AG033514, R01 AG021155]; University of Wisconsin Institute for Clinical and Translational Research; National Center for Research Resources/National Institutes of Health Clinical and Translational Science Award [1UL1RR025011]; program of the National Center for Research Resources, United States National Institutes of Health; Veteran's Administration [I01CX000165]; Waisman Center Core grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development [P30 HD003352-45] FX This project was supported by the Alzheimer's Association, NIRG-09-132626, the National Institute on Aging (R01 AG037639 [BBB], R01 AG027161 [MAS], ADRC P50 AG033514 [SA], R01 AG021155 [SCJ], the University of Wisconsin Institute for Clinical and Translational Research, funded through a National Center for Research Resources/National Institutes of Health Clinical and Translational Science Award, 1UL1RR025011, a program of the National Center for Research Resources, United States National Institutes of Health), by the Veteran's Administration [I01CX000165], and by the Waisman Center Core grant P30 HD003352-45 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The project was also facilitated by the facilities and resources at the Geriatric Research, Education and Clinical Center (GRECC) of the William S. Middleton Memorial Veterans Hospital, Madison, WI (GRECC MS # 2013-08). The authors gratefully acknowledge Nancy Davenport-Sis, Amy Hawley, Sandra Harding, Caitlin Cleary, Jennifer Bond, Jennifer Oh, and Chuck Illingworth, and the support of researchers and staff at the Waisman Center, University of Wisconsin-Madison, for their assistance in recruitment, data collection, and data analysis. Above all, we wish to thank our dedicated volunteers for their participation in this research. NR 162 TC 13 Z9 13 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2014 VL 4 BP 730 EP 742 DI 10.1016/j.nicl.2014.04.008 PG 13 WC Neuroimaging SC Neurosciences & Neurology GA CB5LD UT WOS:000349667600080 PM 24936424 ER PT J AU Fenton, M Whiteside, TL Ferrone, S Boyiadzis, M AF Fenton, Moon Whiteside, Theresa L. Ferrone, Soldano Boyiadzis, Michael TI Chondroitin Sulfate Proteoglycan-4 (CSPG4)-Specific Monoclonal Antibody 225.28 in Detection of Acute Myeloid Leukemia Blasts SO ONCOLOGY RESEARCH LA English DT Article DE Chondroitin sulfate proteoglycan-4 (CSPG4); Acute myeloid leukemia (AML); Monoclonal antibody (mAb) 225.28; Cytogenetic and molecular abnormalities ID MELANOMA-ASSOCIATED ANTIGEN; CELL-SURFACE; POOR-PROGNOSIS; HMW-MAA; NG2; EXPRESSION; 11Q23; ABNORMALITIES; MIMICRY; MK2-23 AB Chondroitin sulfate proteoglycan-4 (CSPG4), a membrane-bound proteoglycan known to be expressed on the surface of malignant cells, has a restricted distribution in normal tissues. CSPG4 is a potential candidate tumor marker. We investigate CSPG4 expression on blasts in newly diagnosed acute myeloid leukemia (AML) patients and its relation with cytogenetic abnormalities and molecular markers known to have prognostic significance in this disease. Using hybridoma technology, we generated a specific monoclonal antibody (mAb), mAb 225.28, reactive with CSPG4. Blast samples obtained from the peripheral blood of newly diagnosed AML patients were analyzed for CSPG4 expression using the CSPG4-specific mAb and multiparameter flow cytometry. The results were correlated with cytogenetic and molecular characteristics of AML. CSPG4 was found to be expressed on a variable fraction of leukemic blasts in all AML patients with different leukemia morphology, including monoblastic cases. Reactivity of CSPG4-specific mAb with leukemic blasts was not limited to those with the rearranged MLL gene. CSPG4 was also expressed on AML blasts with a complex karyotype, FLT3 mutation, or NPM1 mutation. The results indicate that CSPG4 is expressed and detectable by flow cytometry using the mAb 225.28 on a proportion of blasts of all subtypes of AML irrespective of cytogenetic and molecular abnormalities. mAb 225.28 could be useful in detecting AML blasts by flow cytometry. C1 [Fenton, Moon; Whiteside, Theresa L.; Boyiadzis, Michael] Univ Pittsburgh, Sch Med, Inst Canc, Div Hematol & Oncol, Pittsburgh, PA 15232 USA. [Ferrone, Soldano] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Boyiadzis, M (reprint author), Univ Pittsburgh, Sch Med, Inst Canc, Div Hematol & Oncol, 5150 Ctr Ave,Suite 564, Pittsburgh, PA 15232 USA. EM boyiadzism@upmc.edu NR 17 TC 1 Z9 1 U1 1 U2 3 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0965-0407 EI 1555-3906 J9 ONCOL RES JI Oncol. Res. PY 2014 VL 22 IS 2 BP 117 EP 121 DI 10.3727/096504014X14174484758503 PG 5 WC Oncology SC Oncology GA CC0EE UT WOS:000350007800006 PM 25706398 ER PT J AU Pathak, V Dhyani, M Dhyani, P Sharma, P AF Pathak, Vishwambhar Dhyani, Manish Dhyani, Praveen Sharma, Praveen GP IEEE TI Circular Morphological Feature Extraction for Nuclear Medicine Facilitation SO 2014 RECENT ADVANCES AND INNOVATIONS IN ENGINEERING (ICRAIE) LA English DT Proceedings Paper CT IEEE International Conference on Recent Advances and Innovations in Engineering (ICRAIE) CY MAY 09-11, 2014 CL Poornima Univ, Jaipur, INDIA SP IEEE, Poornima Coll Engn HO Poornima Univ DE image description; circular feature extraction; Semi-supervised feature extraction; nuclear medicine; morphological cytopathology ID SEGMENTATION; CIRCLES; IMAGES AB Nuclear medicine applications of computing have largely been on demand due to expensive and time consuming pathological processes for detection of diseases like cancer. Automation tools exploiting morphological characteristics have been employed successfully. Limitations of the existing automated tools in handling specific situations keep the domain alive for research aimed at effective solutions. Detection and counting of circular regions representing the blood cells or bacterial nuclei is an important task in such solutions. The paper investigates traditional image processing methods like region-thresholding, circular Hough transform, Gabor Annulus and Otsu's discriminant in handling of overlapping regions. The paper contributes a semi-supervised method for circular feature extraction and automatic counting. The method is shown to have an edge over existing methods. C1 [Pathak, Vishwambhar] BIT MESRA Jaipur Campus, Jaipur, Rajasthan, India. [Dhyani, Manish] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dhyani, Praveen] Banasthali Univ Jaipur Campus, Jaipur, Rajasthan, India. [Sharma, Praveen] CISCO, San Jose, CA 76437 USA. RP Pathak, V (reprint author), BIT MESRA Jaipur Campus, Jaipur, Rajasthan, India. FU USA FX We acknowledge the motivation and support of Dr. William C. Faquin, USA to take up the work. NR 24 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-4040-0 PY 2014 PG 6 WC Engineering, Multidisciplinary; Engineering, Electrical & Electronic SC Engineering GA BC0TF UT WOS:000349529500131 ER PT J AU Napadow, V Harris, RE AF Napadow, Vitaly Harris, Richard E. TI What has functional connectivity and chemical neuroimaging in fibromyalgia taught us about the mechanisms and management of 'centralized' pain? SO ARTHRITIS RESEARCH & THERAPY LA English DT Review ID MAGNETIC-RESONANCE-SPECTROSCOPY; INTRINSIC BRAIN CONNECTIVITY; DEFAULT MODE NETWORK; N-ACETYLASPARTATE; MR SPECTROSCOPY; CLINICAL PAIN; CORTEX; GLUTAMATE; H-1-MRS; GLUTAMATE/GLUTAMINE AB Research suggests that fibromyalgia is a central, widespread pain syndrome supported by a generalized disturbance in central nervous system pain processing. Over the past decades, multiple lines of research have identified the locus for many functional, chronic pain disorders to the central nervous system, and the brain. In recent years, brain neuroimaging techniques have heralded a revolution in our understanding of chronic pain, as they have allowed researchers to non-invasively (or minimally invasively) evaluate human patients suffering from various pain disorders. While many neuroimaging techniques have been developed, growing interest in two specific imaging modalities has led to significant contributions to chronic pain research. For instance, resting functional connectivity magnetic resonance imaging (fcMRI) is a recent adaptation of fMRI that examines intrinsic brain connectivity - defined as synchronous oscillations of the fMRI signal that occurs in the resting basal state. Proton magnetic resonance spectroscopy (H-1-MRS) is a non-invasive magnetic resonance imaging technique that can quantify the concentration of multiple metabolites within the human brain. This review will outline recent applications of the complementary imaging techniques - fcMRI and H-1-MRS - to improve our understanding of fibromyalgia pathophysiology and how pharmacological and non-pharmacological therapies contribute to analgesia in these patients. A better understanding of the brain in chronic pain, with specific linkage as to which neural processes relate to spontaneous pain perception and hyperalgesia, will greatly improve our ability to develop novel therapeutics. Neuroimaging will play a growing role in the translational research approaches needed to make this a reality. C1 [Napadow, Vitaly] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. [Napadow, Vitaly] Kyung Hee Univ, Dept Biomed Engn, Yongin 446701, South Korea. [Harris, Richard E.] Univ Michigan, Dept Anesthesiol, Chron Pain & Fatigue Res Ctr, Ann Arbor, MI 48106 USA. RP Harris, RE (reprint author), Univ Michigan, Dept Anesthesiol, Chron Pain & Fatigue Res Ctr, Ann Arbor, MI 48106 USA. EM reharris@med.umich.edu FU NCCIH NIH HHS [R01-AT007550, P01-AT006663, P01 AT006663, R01 AT007550]; NIAMS NIH HHS [R01 AR064367, R01-AR064367]; NIDDK NIH HHS [R21 DK097499] NR 52 TC 16 Z9 16 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2014 VL 16 IS 5 AR 425 DI 10.1186/s13075-014-0425-0 PG 8 WC Rheumatology SC Rheumatology GA CB8NC UT WOS:000349885900006 PM 25606591 ER PT S AU Park, EJ Shimaoka, M AF Park, Eun Jeong Shimaoka, Motomu BE Islas, LD Qin, F TI Activation of Leukocyte Integrins SO THERMAL SENSORS SE Current Topics in Membranes LA English DT Review; Book Chapter ID I-LIKE DOMAIN; FUNCTION-ASSOCIATED ANTIGEN-1; T-CELL; STRUCTURAL BASIS; CONFORMATIONAL REGULATION; CRYSTAL-STRUCTURE; LYMPH-NODES; EXTRACELLULAR SEGMENT; ADHESION DEFICIENCY; DENDRITIC CELLS C1 [Park, Eun Jeong; Shimaoka, Motomu] Childrens Hosp, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP Park, EJ (reprint author), Childrens Hosp, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA 02115 USA. NR 86 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1063-5823 BN 978-0-12-800181-3 J9 CURR TOP MEMBR JI Curr. Top. Membr. PY 2014 VL 74 BP 115 EP 132 DI 10.1016/S1063-5823(09)64004-7 PG 18 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BC0RG UT WOS:000349393200005 ER PT B AU Haggarty, SJ Singh, K Perlis, RH Karmacharya, R AF Haggarty, Stephen J. Singh, Karun Perlis, Roy H. Karmacharya, Rakesh BE Hoppler, S Moon, RT TI Wnt Signaling in Mood and Psychotic Disorders SO WNT SIGNALING IN DEVELOPMENT AND DISEASE: MOLECULAR MECHANISMS AND BIOLOGICAL FUNCTIONS LA English DT Article; Book Chapter ID GLYCOGEN-SYNTHASE KINASE-3; GRAY-MATTER VOLUME; LITHIUM-SENSITIVE BEHAVIORS; CIRCADIAN CLOCK GENE; BIPOLAR DISORDER; BETA-CATENIN; IN-VIVO; DOPAMINE-D-2 RECEPTOR; VALPROIC ACID; MUTANT MICE C1 [Haggarty, Stephen J.] Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA. [Haggarty, Stephen J.; Perlis, Roy H.; Karmacharya, Rakesh] Harvard Univ, Sch Med, Boston, MA USA. [Haggarty, Stephen J.; Perlis, Roy H.; Karmacharya, Rakesh] Massachusetts Gen Hosp, Dept Psychiat, Ctr Human Genet Res, Boston, MA 02114 USA. [Haggarty, Stephen J.; Perlis, Roy H.; Karmacharya, Rakesh] Massachusetts Gen Hosp, Ctr Human Genet Res, MGH Psychiat Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA. [Singh, Karun] McMaster Univ, Dept Biochem & Biomed Sci, McMaster Stem Cell & Canc Res Inst, Hamilton, ON L8N 3Z5, Canada. [Karmacharya, Rakesh] Broad Inst Harvard & MIT, Chem Biol Program, Cambridge, MA USA. [Karmacharya, Rakesh] McLean Hosp, Schizophrenia & Bipolar Disorder Program, Belmont, MA 02178 USA. RP Haggarty, SJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA. NR 86 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA BN 978-1-118-44409-2; 978-1-118-44416-0 PY 2014 BP 379 EP 391 D2 10.1002/9781118444122 PG 13 WC Biochemistry & Molecular Biology; Physiology SC Biochemistry & Molecular Biology; Physiology GA BB9MO UT WOS:000348498000033 ER PT B AU Haggarty, SJ Singh, K Perlis, RH Karmacharya, R AF Haggarty, Stephen J. Singh, Karun Perlis, Roy H. Karmacharya, Rakesh BE Hoppler, S Moon, RT TI Neuropsychiatric Disease-Associated Genetic Variation in the Wnt Pathway SO WNT SIGNALING IN DEVELOPMENT AND DISEASE: MOLECULAR MECHANISMS AND BIOLOGICAL FUNCTIONS LA English DT Article; Book Chapter ID FRAGILE-X-SYNDROME; DE-NOVO MUTATIONS; PITT-HOPKINS-SYNDROME; AUTISM SPECTRUM DISORDERS; 22Q11.2 DELETION SYNDROME; GENOME-WIDE ASSOCIATION; HISTONE H1 RECRUITMENT; COPY NUMBER VARIATION; BETA-CATENIN; MOUSE MODEL C1 [Haggarty, Stephen J.] Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA. [Haggarty, Stephen J.; Perlis, Roy H.; Karmacharya, Rakesh] Harvard Univ, Sch Med, Boston, MA USA. [Haggarty, Stephen J.; Perlis, Roy H.; Karmacharya, Rakesh] Massachusetts Gen Hosp, Dept Psychiat, Ctr Human Genet Res, Boston, MA 02114 USA. [Haggarty, Stephen J.; Perlis, Roy H.; Karmacharya, Rakesh] Massachusetts Gen Hosp, Ctr Human Genet Res, MGH Psychiat Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA. [Singh, Karun] McMaster Univ, Dept Biochem & Biomed Sci, McMaster Stem Cell & Canc Res Inst, Hamilton, ON L8N 3Z5, Canada. [Karmacharya, Rakesh] Broad Inst Harvard & MIT, Chem Biol Program, Cambridge, MA USA. [Karmacharya, Rakesh] McLean Hosp, Schizophrenia & Bipolar Disorder Program, Belmont, MA 02178 USA. RP Haggarty, SJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA. NR 120 TC 0 Z9 0 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA BN 978-1-118-44409-2; 978-1-118-44416-0 PY 2014 BP 393 EP 409 D2 10.1002/9781118444122 PG 17 WC Biochemistry & Molecular Biology; Physiology SC Biochemistry & Molecular Biology; Physiology GA BB9MO UT WOS:000348498000034 ER PT B AU Haggarty, SJ AF Haggarty, Stephen J. BE Hoppler, S Moon, RT TI Wnt Signaling in Dementia SO WNT SIGNALING IN DEVELOPMENT AND DISEASE: MOLECULAR MECHANISMS AND BIOLOGICAL FUNCTIONS LA English DT Article; Book Chapter ID REDUCES TAU PHOSPHORYLATION; AMYLOID PRECURSOR PROTEIN; GENOME-WIDE ASSOCIATION; ALZHEIMERS-DISEASE; IDENTIFIES VARIANTS; INHIBITION; LITHIUM; DICKKOPF-1; DEGENERATION; PATHWAYS C1 [Haggarty, Stephen J.] Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA. [Haggarty, Stephen J.] Harvard Univ, Sch Med, Boston, MA USA. [Haggarty, Stephen J.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Human Genet Res, Boston, MA 02114 USA. [Haggarty, Stephen J.] Massachusetts Gen Hosp, Ctr Human Genet Res, MGH Psychiat Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA. RP Haggarty, SJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA. NR 58 TC 0 Z9 0 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA BN 978-1-118-44409-2; 978-1-118-44416-0 PY 2014 BP 411 EP 420 D2 10.1002/9781118444122 PG 10 WC Biochemistry & Molecular Biology; Physiology SC Biochemistry & Molecular Biology; Physiology GA BB9MO UT WOS:000348498000035 ER PT S AU Shen, L Song, CX He, C Zhang, Y AF Shen, Li Song, Chun-Xiao He, Chuan Zhang, Yi BE Kornberg, RD TI Mechanism and Function of Oxidative Reversal of DNA and RNA Methylation SO ANNUAL REVIEW OF BIOCHEMISTRY, VOL 83 SE Annual Review of Biochemistry LA English DT Review; Book Chapter DE DNA/RNA demethylation; 5-methylcytosine oxidation; Fe(II)/alpha-ketoglutarate-dependent dioxygenases; Tet; N-6-methyladenosine ID EMBRYONIC STEM-CELLS; PRIMORDIAL GERM-CELLS; BASE EXCISION-REPAIR; MEDIATED 5-METHYLCYTOSINE OXIDATION; ACETYLGLUCOSAMINE TRANSFERASE OGT; MOUSE PREIMPLANTATION DEVELOPMENT; ACUTE MYELOID-LEUKEMIA; TRANSLOCATION 1 TET1; GENOME-WIDE ANALYSIS; THYMINE DNA AB The importance of eukaryotic DNA methylation [5-methylcytosine (5mC)] in transcriptional regulation and development was first suggested almost 40 years ago. However, the molecular mechanism underlying the dynamic nature of this epigenetic mark was not understood until recently, following the discovery that the TET proteins, a family of AlkB-like Fe(II)/alpha-ketoglutarate-dependent dioxygenases, can oxidize 5mC to generate 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Since then, several mechanisms that are responsible for processing oxidized 5mC derivatives to achieve DNA demethylation have emerged. Our biochemical understanding of the DNA demethylation process has prompted new investigations into the biological functions of DNA demethylation. Characterization of two additional AlkB family proteins, FTO and ALKBH5, showed that they possess demethylase activity toward N-6-methyladenosine (m(6)A) in RNA, indicating that members of this subfamily of dioxygenases have a general function in demethylating nucleic acids. In this review, we discuss recent advances in this emerging field, focusing on the mechanism and function of TET-mediated DNA demethylation. C1 [Shen, Li; Zhang, Yi] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Shen, Li; Zhang, Yi] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Shen, Li; Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Song, Chun-Xiao; He, Chuan] Univ Chicago, Dept Chem, Chicago, IL 60637 USA. [Song, Chun-Xiao; He, Chuan] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA. RP Shen, L (reprint author), Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. EM chuanhe@uchicago.edu; yzhang@genetics.med.harvard.edu FU Howard Hughes Medical Institute; NHGRI NIH HHS [HG006827, R01 HG006827]; NIDDK NIH HHS [U01 DK089565, U01DK089565]; NIGMS NIH HHS [GM071440, GM68804, R01 GM068804, R01 GM071440] NR 178 TC 76 Z9 77 U1 9 U2 41 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4154 BN 978-0-8243-0883-4 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem.. PY 2014 VL 83 BP 585 EP + DI 10.1146/annurev-biochem-060713-035513 PG 31 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BB9LE UT WOS:000348432500023 PM 24905787 ER PT S AU Blain, JC Szostak, JW AF Blain, J. Craig Szostak, Jack W. BE Kornberg, RD TI Progress Toward Synthetic Cells SO ANNUAL REVIEW OF BIOCHEMISTRY, VOL 83 SE Annual Review of Biochemistry LA English DT Review; Book Chapter DE protocells; artificial life; origin of life; self-replication; evolution ID TEMPLATE-DIRECTED SYNTHESIS; PEPTIDE NUCLEIC-ACIDS; CATALYZED RNA POLYMERIZATION; CHEMICAL PRIMER EXTENSION; SELF-REPRODUCING VESICLES; MODEL PROTOCELL MEMBRANES; COMPLEMENTARY-STRAND RNA; NEAREST-NEIGHBOR MODEL; IN-VITRO EVOLUTION; HAIRPIN OLIGONUCLEOTIDES AB The complexity of even the simplest known life forms makes efforts to synthesize living cells from inanimate components seem like a daunting task. However, recent progress toward the creation of synthetic cells, ranging from simple protocells to artificial cells approaching the complexity of bacteria, suggests that the synthesis of life is now a realistic goal. Protocell research, fueled by advances in the biophysics of primitive membranes and the chemistry of nucleic acid replication, is providing new insights into the origin of cellular life. Parallel efforts to construct more complex artificial cells, incorporating translational machinery and protein enzymes, are providing information about the requirements for protein-based life. We discuss recent advances and remaining challenges in the synthesis of artificial cells, the possibility of creating new forms of life distinct from existing biology, and the promise of this research for gaining a deeper understanding of the nature of living systems. C1 [Blain, J. Craig] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Blain, JC (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. EM craig@jcraigblain.com; szostak@molbio.mgh.harvard.edu FU Howard Hughes Medical Institute NR 213 TC 44 Z9 48 U1 21 U2 111 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4154 BN 978-0-8243-0883-4 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem.. PY 2014 VL 83 BP 615 EP 640 DI 10.1146/annurev-biochem-080411-124036 PG 26 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BB9LE UT WOS:000348432500024 PM 24606140 ER PT S AU Yarmush, ML Golberg, A Sersa, G Kotnik, T Miklavcic, D AF Yarmush, Martin L. Golberg, Alexander Sersa, Gregor Kotnik, Tadej Miklavcic, Damijan BE Yarmush, ML TI Electroporation-Based Technologies for Medicine: Principles, Applications, and Challenges SO ANNUAL REVIEW OF BIOMEDICAL ENGINEERING, VOL 16 SE Annual Review of Biomedical Engineering LA English DT Review; Book Chapter DE pulsed electric field; electropermeabilization; electrochemotherapy; gene electrotransfer; DNA vaccination; irreversible electroporation ID ELECTRICAL-IMPEDANCE TOMOGRAPHY; STANDARD OPERATING PROCEDURES; TRANSDERMAL DRUG-DELIVERY; CYTOTOXIC T-LYMPHOCYTES; 1ST CLINICAL-TRIAL; SINGLE-CELL LEVEL; LOW-VOLTAGE PULSE; IRREVERSIBLE ELECTROPORATION; IN-VIVO; GENE ELECTROTRANSFER AB When high-amplitude, short-duration pulsed electric fields are applied to cells and tissues, the permeability of the cell membranes and tissue is increased. This increase in permeability is currently explained by the temporary appearance of aqueous pores within the cell membrane, a phenomenon termed electroporation. During the past four decades, advances in fundamental and experimental electroporation research have allowed for the translation of electroporation-based technologies to the clinic. In this review, we describe the theory and current applications of electroporation in medicine and then discuss current challenges in electroporation research and barriers to a more extensive spread of these clinical applications. C1 [Yarmush, Martin L.; Golberg, Alexander] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Dept Surg, Boston, MA 02114 USA. [Yarmush, Martin L.; Golberg, Alexander] Shriners Burn Hosp Children, Boston, MA 02114 USA. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. [Sersa, Gregor] Inst Oncol Ljubljana, Dept Expt Oncol, SI-1000 Ljubljana, Slovenia. [Kotnik, Tadej; Miklavcic, Damijan] Univ Ljubljana, Fac Elect Engn, Dept Biomed Engn, SI-1000 Ljubljana, Slovenia. RP Yarmush, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Dept Surg, Boston, MA 02114 USA. EM ireis@sbi.org; damijan.miklavcic@fe.uni-lj.si OI Kotnik, Tadej/0000-0002-0777-9948 NR 180 TC 110 Z9 114 U1 3 U2 43 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1523-9829 BN 978-0-8243-3516-8 J9 ANNU REV BIOMED ENG JI Annu. Rev. Biomed. Eng. PY 2014 VL 16 BP 295 EP 320 DI 10.1146/annurev-bioeng-071813-104622 PG 26 WC Engineering, Biomedical SC Engineering GA BB9LF UT WOS:000348433000012 PM 24905876 ER PT S AU Jain, RK Martin, JD Stylianopoulos, T AF Jain, Rakesh K. Martin, John D. Stylianopoulos, Triantafyllos BE Yarmush, ML TI The Role of Mechanical Forces in Tumor Growth and Therapy SO ANNUAL REVIEW OF BIOMEDICAL ENGINEERING, VOL 16 SE Annual Review of Biomedical Engineering LA English DT Review; Book Chapter DE tumor microenvironment; vessel compression; solid stress; vascular hyperpermeability; tumor perfusion; vascular normalization; stress alleviation ID INTERSTITIAL FLUID PRESSURE; ANTI-ANGIOGENIC THERAPY; SOLID TUMORS; BLOOD-FLOW; VASCULAR NORMALIZATION; GLIOBLASTOMA PATIENTS; CANCER-CELLS; ANTIANGIOGENIC THERAPY; LYMPHATIC CAPILLARIES; EXTRACELLULAR-MATRIX AB Tumors generate physical forces during growth and progression. These physical forces are able to compress blood and lymphatic vessels, reducing perfusion rates and creating hypoxia. When exerted directly on cancer cells, they can increase cells' invasive and metastatic potential. Tumor vessels-while nourishing the tumor-are usually leaky and tortuous, which further decreases perfusion. Hypoperfusion and hypoxia contribute to immune evasion, promote malignant progression and metastasis, and reduce the efficacy of a number of therapies, including radiation. In parallel, vessel leakiness together with vessel compression causes a uniformly elevated interstitial fluid pressure that hinders delivery of blood-borne therapeutic agents, lowering the efficacy of chemo- and nanotherapies. In addition, shear stresses exerted by flowing blood and interstitial fluid modulate the behavior of cancer and a variety of host cells. Taming these physical forces can improve therapeutic outcomes in many cancers. C1 [Jain, Rakesh K.; Martin, John D.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Jain, Rakesh K.; Martin, John D.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Martin, John D.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Stylianopoulos, Triantafyllos] Univ Cyprus, Dept Mech & Mfg Engn, Canc Biophys Lab, CY-1678 Nicosia, Cyprus. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu; tstylian@ucy.ac.cy RI Martin, John/L-6892-2016; OI Martin, John/0000-0002-9828-8203; Stylianopoulos, Triantafyllos/0000-0002-3093-1696 FU European Research Council [336839]; NCI NIH HHS [P01-CA080124, P01 CA080124, P50 CA165962, R01 CA085140, R01 CA096915, R01 CA098706, R01 CA115767, R01 CA126642, R01-CA085140, R01-CA096915, R01-CA098706, R01-CA115767, R01-CA126642, T32 CA073479, T32-CA0734]; NIBIB NIH HHS [P41 EB015903] NR 151 TC 65 Z9 66 U1 9 U2 53 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1523-9829 BN 978-0-8243-3516-8 J9 ANNU REV BIOMED ENG JI Annu. Rev. Biomed. Eng. PY 2014 VL 16 BP 321 EP 346 DI 10.1146/annurev-bioeng-071813-105259 PG 26 WC Engineering, Biomedical SC Engineering GA BB9LF UT WOS:000348433000013 PM 25014786 ER PT S AU Martel, JM Toner, M AF Martel, Joseph M. Toner, Mehmet BE Yarmush, ML TI Inertial Focusing in Microfluidics SO ANNUAL REVIEW OF BIOMEDICAL ENGINEERING, VOL 16 SE Annual Review of Biomedical Engineering LA English DT Review; Book Chapter DE high throughput; particle separation; label-free cell separation; biofluid processing; hydrodynamic lift; applied physics ID DETERMINISTIC LATERAL DISPLACEMENT; CONTINUOUS PARTICLE SEPARATION; ON-A-CHIP; CELL-SEPARATION; POISEUILLE FLOW; REYNOLDS-NUMBER; SINGLE-CELLS; PIPE-FLOW; VISCOELASTIC FLUIDS; SPHERICAL-PARTICLES AB When Segre and Silberberg in 1961 witnessed particles in a laminar pipe flow congregating at an annulus in the pipe, scientists were perplexed and spent decades learning why such behavior occurred, finally understanding that it was caused by previously unknown forces on particles in an inertial flow. The advent of microfluidics opened a new realm of possibilities for inertial focusing in the processing of biological fluids and cellular suspensions and created a field that is now rapidly expanding. Over the past five years, inertial focusing has enabled high-throughput, simple, and precise manipulation of bodily fluids for a myriad of applications in point-of-care and clinical diagnostics. This review describes the theoretical developments that have made the field of inertial focusing what it is today and presents the key applications that will make inertial focusing a mainstream technology in the future. C1 [Martel, Joseph M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, BioMEMS Resource Ctr,Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Martel, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, BioMEMS Resource Ctr,Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. EM mtoner@hms.harvard.edu FU NIBIB NIH HHS [P41 EB002503, U01 EB012493] NR 114 TC 59 Z9 59 U1 14 U2 79 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1523-9829 BN 978-0-8243-3516-8 J9 ANNU REV BIOMED ENG JI Annu. Rev. Biomed. Eng. PY 2014 VL 16 BP 371 EP 396 DI 10.1146/annurev-bioeng-121813-120704 PG 26 WC Engineering, Biomedical SC Engineering GA BB9LF UT WOS:000348433000015 PM 24905880 ER PT S AU Ginat, DT Gupta, R AF Ginat, Daniel Thomas Gupta, Rajiv BE Yarmush, ML TI Advances in Computed Tomography Imaging Technology SO ANNUAL REVIEW OF BIOMEDICAL ENGINEERING, VOL 16 SE Annual Review of Biomedical Engineering LA English DT Review; Book Chapter DE extreme multidetector CT; iterative reconstruction; dual-energy CT; cone-beam CT; portable CT; phase-contrast CT ID STATISTICAL ITERATIVE RECONSTRUCTION; DUAL-ENERGY CT; CONE-BEAM CT; FILTERED BACK-PROJECTION; RADIATION-DOSE REDUCTION; INTENSIVE-CARE-UNIT; PANEL VOLUME CT; HEAD CT; CLINICAL-APPLICATIONS; ABDOMINAL CT AB Computed tomography (CT) is an essential tool in diagnostic imaging for evaluating many clinical conditions. In recent years, there have been several notable advances in CT technology that already have had or are expected to have a significant clinical impact, including extreme multidetector CT, iterative reconstruction algorithms, dual-energy CT, cone-beam CT, portable CT, and phase-contrast CT. These techniques and their clinical applications are reviewed and illustrated in this article. In addition, emerging technologies that address deficiencies in these modalities are discussed. C1 [Ginat, Daniel Thomas] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Gupta, Rajiv] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Ginat, DT (reprint author), Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. EM rgupta1@partners.org NR 83 TC 9 Z9 9 U1 3 U2 21 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1523-9829 BN 978-0-8243-3516-8 J9 ANNU REV BIOMED ENG JI Annu. Rev. Biomed. Eng. PY 2014 VL 16 BP 431 EP 453 DI 10.1146/annurev-bioeng-121813-113601 PG 23 WC Engineering, Biomedical SC Engineering GA BB9LF UT WOS:000348433000018 PM 25014788 ER PT S AU Van Tyne, D Gilmore, MS AF Van Tyne, Daria Gilmore, Michael S. BE Gottesman, S TI Friend Turned Foe: Evolution of Enterococcal Virulence and Antibiotic Resistance SO ANNUAL REVIEW OF MICROBIOLOGY, VOL 68 SE Annual Review of Microbiology LA English DT Review; Book Chapter DE Enterococcus; genomics; human-associated microbial flora ID COLLAGEN-BINDING MSCRAMM; ANTIMICROBIAL RESISTANCE; STREPTOCOCCUS-FAECALIS; STAPHYLOCOCCUS-AUREUS; AGGREGATION SUBSTANCE; SURFACE PROTEIN; PATHOGENICITY ISLAND; COLONIZATION RESISTANCE; INTESTINAL COLONIZATION; VANCOMYCIN RESISTANCE AB The enterococci are an ancient genus that evolved along with the tree of life. These intrinsically rugged bacteria are highly adapted members of the intestinal consortia of a range of hosts that spans the animal kingdom. Enterococci are also leading opportunistic hospital pathogens, causing infections that are often resistant to treatment with most antibiotics. Despite the importance of enterococci as hospital pathogens, the vast majority live outside of humans, and nearly all of their evolutionary history took place before the appearance of modern humans. Because hospital infections represent evolutionary end points, traits that exacerbate human infection are unlikely to have evolved for that purpose. However, clusters of traits have converged in specific lineages that are well adapted to colonize the antibiotic-perturbed gastrointestinal tracts of patients and that thrive in the hospital environment. Here we discuss these traits in an evolutionary context, as well as how comparative genomics is providing new insights into the evolution of the enterococci. C1 [Van Tyne, Daria] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. RP Van Tyne, D (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM vantyne@fas.harvard.edu; michael_gilmore@meei.harvard.edu FU NEI NIH HHS [EY007145, T32 EY007145]; NIAID NIH HHS [AI072360, AI083214, AI108710, P01 AI083214, R01 AI072360, R01 AI108710] NR 133 TC 18 Z9 18 U1 2 U2 22 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4227 BN 978-0-8243-1168-1 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 2014 VL 68 BP 337 EP 356 DI 10.1146/annurev-micro-091213-113003 PG 20 WC Microbiology SC Microbiology GA BB9LU UT WOS:000348452900019 PM 25002090 ER PT S AU Fox, PT Lancaster, JL Laird, AR Eickhoff, SB AF Fox, Peter T. Lancaster, Jack L. Laird, Angela R. Eickhoff, Simon B. BE Hyman, SE TI Meta-Analysis in Human Neuroimaging: Computational Modeling of Large-Scale Databases SO ANNUAL REVIEW OF NEUROSCIENCE, VOL 37 SE Annual Review of Neuroscience LA English DT Review; Book Chapter DE human brain mapping; activation likelihood estimation; ALE; magnetic resonance imaging; MRI; fMRI ID POSITRON-EMISSION-TOMOGRAPHY; LIKELIHOOD ESTIMATION METAANALYSIS; ACTIVATION-BASED PARCELLATION; FUNCTIONAL IMAGING DATA; HUMAN VISUAL-CORTEX; HUMAN-BRAIN; ALE METAANALYSIS; WORKING-MEMORY; HUMAN AMYGDALA; PET IMAGES AB Spatial normalization-applying standardized coordinates as anatomical addresses within a reference space-was introduced to human neuroimaging research nearly 30 years ago. Over these three decades, an impressive series of methodological advances have adopted, extended, and popularized this standard. Collectively, this work has generated a methodologically coherent literature of unprecedented rigor, size, and scope. Large-scale online databases have compiled these observations and their associated meta-data, stimulating the development ofmeta-analytic methods to exploit this expanding corpus. Coordinate-based meta-analytic methods have emerged and evolved in rigor and utility. Early methods computed cross-study consensus, in a manner roughly comparable to traditional (nonimaging) meta-analysis. Recent advances now compute coactivation-based connectivity, connectivity-based functional parcellation, and complex network models powered from data sets representing tens of thousands of subjects. Meta-analyses of human neuroimaging data in large-scale databases now stand at the forefront of computational neurobiology. C1 [Fox, Peter T.; Lancaster, Jack L.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Fox, Peter T.; Lancaster, Jack L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Fox, Peter T.] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Pokfulam, Hong Kong, Peoples R China. [Laird, Angela R.] Florida Int Univ, Dept Phys, Miami, FL 33199 USA. [Eickhoff, Simon B.] Univ Dusseldorf, Inst Clin Neurosci & Med Psychol, D-40225 Dusseldorf, Germany. RP Fox, PT (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. EM Fox@uthscsa.edu; jlancaster@uthscsa.edu; angie.laird@fiu.edu; simon.b.eickhoff@gmail.com RI Fox, Peter/B-4725-2010 OI Fox, Peter/0000-0002-0465-2028 FU NCRR NIH HHS [RR024387]; NIAAA NIH HHS [AA019691, R01 AA019691]; NIBIB NIH HHS [R01 EB015314, EB015314]; NIMH NIH HHS [MH084812, MH74457, R01 MH074457, R01 MH084812]; NINDS NIH HHS [NS062254, R21 NS062254] NR 108 TC 29 Z9 31 U1 2 U2 7 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0147-006X BN 978-0-8243-2437-7 J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 2014 VL 37 BP 409 EP 434 DI 10.1146/annurev-neuro-062012-170320 PG 26 WC Neurosciences SC Neurosciences & Neurology GA BB9LX UT WOS:000348454500021 PM 25032500 ER PT J AU Johnson, N Dudbridge, F Orr, N Gibson, L Jones, ME Schoemaker, MJ Folkerd, EJ Haynes, BP Hopper, JL Southey, MC Dite, GS Apicella, C Schmidt, MK Broeks, A Van't Veer, LJ Atsma, F Muir, K Lophatananon, A Fasching, PA Beckmann, MW Ekici, AB Renner, SP Sawyer, E Tomlinson, I Kerin, M Miller, N Burwinkel, B Marme, F Schneeweiss, A Sohn, C Guenel, P Truong, T Cordina, E Menegaux, F Bojesen, SE Nordestgaard, BG Flyger, H Milne, R Zamora, MP Perez, JIA Benitez, J Bernstein, L Anton-Culver, H Ziogas, A Dur, CC Brenner, H Muller, H Arndt, V Dieffenbach, AK Meindl, A Heil, J Bartram, CR Schmutzler, RK Brauch, H Justenhoven, C Ko, YD Nevanlinna, H Muranen, TA Aittomaki, K Blomqvist, C Matsuo, K Dork, T Bogdanova, NV Antonenkova, NN Lindblom, A Mannermaa, A Kataja, V Kosma, VM Hartikainen, JM Chenevix-Trench, G Beesley, J Wu, AH Van den Berg, D Tseng, CC Lambrechts, D Smeets, D Neven, P Wildiers, H Chang-Claude, J Rudolph, A Nickels, S Flesch-Janys, D Radice, P Peterlongo, P Bonanni, B Pensotti, V Couch, FJ Olson, JE Wang, XS Fredericksen, Z Pankratz, VS Giles, GG Severi, G Baglietto, L Haiman, C Simard, J Goldberg, MS Labreche, F Dumont, M Soucy, P Teo, S Yip, CH Phuah, SY Cornes, BK Kristensen, VN Alnaes, GG Borresen-Dale, AL Zheng, W Winqvist, R Pylkas, K Jukkola-Vuorinen, A Grip, M Andrulis, IL Knight, JA Glendon, G Mulligan, AM Devillee, P Figueroa, J Chanock, SJ Lissowska, J Sherman, ME Hall, P Schoof, N Hooning, M Hollestelle, A Oldenburg, RA Tilanus-Linthorst, M Liu, JJ Cox, A Brock, IW Reed, MWR Cross, SS Blot, W Signorello, LB Pharoah, PDP Dunning, AM Shah, M Kang, D Noh, DY Park, SK Choi, JY Hartman, M Miao, H Lim, WY Tang, A Hamann, U Forsti, A Rudiger, T Ulmer, HU Jakubowska, A Lubinski, J Jaworska-Bieniek, K Durda, K Sangrajrang, S Gaborieau, V Brennan, P Mckay, J Slager, S Toland, AE Vachon, C Yannoukakos, D Shen, CY Yu, JC Huang, CS Hou, MF Gonzalez-Neira, A Tessier, DC Vincent, D Bacot, F Luccarini, C Dennis, J Michailidou, K Bolla, MK Wang, J Easton, DF Garcia-Closas, M Dowsett, M Ashworth, A Swerdlow, AJ Peto, J Silva, ID Fletcher, O AF Johnson, Nichola Dudbridge, Frank Orr, Nick Gibson, Lorna Jones, Michael E. Schoemaker, Minouk J. Folkerd, Elizabeth J. Haynes, Ben P. Hopper, John L. Southey, Melissa C. Dite, Gillian S. Apicella, Carmel Schmidt, Marjanka K. Broeks, Annegien Van't Veer, Laura J. Atsma, Femke Muir, Kenneth Lophatananon, Artitaya Fasching, Peter A. Beckmann, Matthias W. Ekici, Arif B. Renner, Stefan P. Sawyer, Elinor Tomlinson, Ian Kerin, Michael Miller, Nicola Burwinkel, Barbara Marme, Frederik Schneeweiss, Andreas Sohn, Christof Guenel, Pascal Truong, Therese Cordina, Emilie Menegaux, Florence Bojesen, Stig E. Nordestgaard, Borge G. Flyger, Henrik Milne, Roger Zamora, M. Pilar Arias Perez, Jose Ignacio Benitez, Javier Bernstein, Leslie Anton-Culver, Hoda Ziogas, Argyrios Dur, Christina Clarke Brenner, Hermann Mueller, Heiko Arndt, Volker Dieffenbach, Aida Karina Meindl, Alfons Heil, Joerg Bartram, Claus R. Schmutzler, Rita K. Brauch, Hiltrud Justenhoven, Christina Ko, Yon-Dschun Nevanlinna, Heli Muranen, Taru A. Aittomaeki, Kristiina Blomqvist, Carl Matsuo, Keitaro Doerk, Thilo Bogdanova, Natalia V. Antonenkova, Natalia N. Lindblom, Annika Mannermaa, Arto Kataja, Vesa Kosma, Veli-Matti Hartikainen, Jaana M. Chenevix-Trench, Georgia Beesley, Jonathan Wu, Anna H. Van den Berg, David Tseng, Chiu-Chen Lambrechts, Diether Smeets, Dominiek Neven, Patrick Wildiers, Hans Chang-Claude, Jenny Rudolph, Anja Nickels, Stefan Flesch-Janys, Dieter Radice, Paolo Peterlongo, Paolo Bonanni, Bernardo Pensotti, Valeria Couch, Fergus J. Olson, Janet E. Wang, Xianshu Fredericksen, Zachary Pankratz, Vernon S. Giles, Graham G. Severi, Gianluca Baglietto, Laura Haiman, Chris Simard, Jacques Goldberg, Mark S. Labreche, France Dumont, Martine Soucy, Penny Teo, Soo Yip, Cheng Har Phuah, Sze Yee Cornes, Belinda K. Kristensen, Vessela N. Alnaes, Grethe Grenaker Borresen-Dale, Anne-Lise Zheng, Wei Winqvist, Robert Pylkaes, Katri Jukkola-Vuorinen, Arja Grip, Mervi Andrulis, Irene L. Knight, Julia A. Glendon, Gord Mulligan, Anna Marie Devillee, Peter Figueroa, Jonine Chanock, Stephen J. Lissowska, Jolanta Sherman, Mark E. Hall, Per Schoof, Nils Hooning, Maartje Hollestelle, Antoinette Oldenburg, Rogier A. Tilanus-Linthorst, Madeleine Liu, Jianjun Cox, Angie Brock, Ian W. Reed, Malcolm W. R. Cross, Simon S. Blot, William Signorello, Lisa B. Pharoah, Paul D. P. Dunning, Alison M. Shah, Mitul Kang, Daehee Noh, Dong-Young Park, Sue K. Choi, Ji-Yeob Hartman, Mikael Miao, Hui Lim, Wei Yen Tang, Anthony Hamann, Ute Foersti, Asta Ruediger, Thomas Ulmer, Hans Ulrich Jakubowska, Anna Lubinski, Jan Jaworska-Bieniek, Katarzyna Durda, Katarzyna Sangrajrang, Suleeporn Gaborieau, Valerie Brennan, Paul Mckay, James Slager, Susan Toland, Amanda E. Vachon, Celine Yannoukakos, Drakoulis Shen, Chen-Yang Yu, Jyh-Cherng Huang, Chiun-Sheng Hou, Ming-Feng Gonzalez-Neira, Anna Tessier, Daniel C. Vincent, Daniel Bacot, Francois Luccarini, Craig Dennis, Joe Michailidou, Kyriaki Bolla, Manjeet K. Wang, Jean Easton, Douglas F. Garcia-Closas, Montserrat Dowsett, Mitch Ashworth, Alan Swerdlow, Anthony J. Peto, Julian Silva, Isabel dos Santos Fletcher, Olivia CA Gene Environm Interaction & Breast KConFab Investigators Australian Ovarian Canc Study Grp TI Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study SO BREAST CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; SEX-HORMONE LEVELS; PREMENOPAUSAL WOMEN; STEROID-HORMONES; SERUM; TWINS; ESTRADIOL; LOCI AB Introduction: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age <= 50 years. Methods: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics. Results: We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P-trend = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P-trend = 0.005) but not cases (P-trend = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P-het = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age >= 15 years (ORhet = 0.84, 95% CI 0.75, 0.94; ORhom = 0.81, 95% CI 0.51, 1.30; P-trend = 0.002) but not for those who had their menarche age <= 11 years (ORhet = 1.06, 95% CI 0.95, 1.19, ORhom = 1.07, 95% CI 0.67, 1.72; P-trend = 0.29). Conclusions: To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels. C1 [Johnson, Nichola; Orr, Nick] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Johnson, Nichola; Orr, Nick] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England. [Dudbridge, Frank; Gibson, Lorna] London Sch Hyg & Trop Med, Non Commun Dis Epidemiol Dept, London WC1E 7HT, England. [Jones, Michael E.; Schoemaker, Minouk J.] Inst Canc Res, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England. [Folkerd, Elizabeth J.; Haynes, Ben P.] Royal Marsden Hosp, Acad Dept Biochem, London SW3 6JJ, England. [Hopper, John L.; Dite, Gillian S.; Apicella, Carmel; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Dept, Melbourne, Vic 3010, Australia. 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[Cox, Angie; Brock, Ian W.] Univ Sheffield, CRUK YCR Sheffield Canc Res Ctr, Dept Oncol, Inst Canc Studies, Sheffield S10 2HQ, S Yorkshire, England. [Reed, Malcolm W. R.] Univ Sheffield, CRUK YCR Sheffield Canc Res Ctr, Dept Oncol, Acad Unit Surg Oncol, Sheffield S10 2HQ, S Yorkshire, England. [Cross, Simon S.] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Sheffield S10 2HQ, S Yorkshire, England. [Blot, William] Int Epidemiol Inst, Rockville, MD 20850 USA. [Signorello, Lisa B.; Miao, Hui] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Signorello, Lisa B.; Miao, Hui] Harvard Univ, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Signorello, Lisa B.] Dana Farber Harvard Canc Ctr, Boston, MA 02215 USA. [Pharoah, Paul D. P.; Dunning, Alison M.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge CB1 8RN, England. [Shah, Mitul; Kang, Daehee; Noh, Dong-Young; Choi, Ji-Yeob] Seoul Natl Univ, Coll Med, Seoul 110799, South Korea. 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[Ulmer, Hans Ulrich] Frauenklin Stadtklin Baden Baden, D-76532 Baden, Switzerland. [Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna] Pomeranian Med Univ, Dept Genet & Pathol, PL-70204 Szczecin, Poland. [Jaworska-Bieniek, Katarzyna] Med Univ Warsaw, Postgrad Sch Mol Med, PL-02091 Warsaw, Poland. [Sangrajrang, Suleeporn] Natl Canc Inst, Bangkok 10400, Thailand. [Gaborieau, Valerie] Int Agcy Res Canc, F-69372 Lyon 08, France. [Toland, Amanda E.] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Yannoukakos, Drakoulis] Natl Ctr Sci Res Demokritos, Mol Diagnost Lab, IRRP, Athens 15310, Greece. [Shen, Chen-Yang] China Med Univ, Coll Publ Hlth, Taichung 40402, Taiwan. [Shen, Chen-Yang] Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan. [Yu, Jyh-Cherng] Tri Serv Gen Hosp, Dept Surg, Taipei 114, Taiwan. [Huang, Chiun-Sheng] Natl Taiwan Univ Hosp, Dept Surg, Taipei 10048, Taiwan. 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EM nichola.johnson@icr.ac.uk RI Gonzalez-Neira, Anna/C-5791-2015; Hartman, Mikael/B-4324-2011; Yip, Cheng-Har/B-1909-2010; Teo, Soo-hwang/H-2353-2014; Hartikainen, Jaana/E-6256-2015; Garcia-Closas, Montserrat /F-3871-2015; Atsma, F./L-4178-2015; Dork, Thilo/J-8620-2012; Bowtell, David/H-1007-2016; Renner, Stefan/F-1158-2014; Brenner, Hermann/B-4627-2017 OI Schoemaker, Minouk/0000-0001-8403-2234; Nevanlinna, Heli/0000-0002-0916-2976; Huang, Chiun-Sheng/0000-0002-6557-211X; Cross, Simon/0000-0003-2044-1754; Dunning, Alison Margaret/0000-0001-6651-7166; Heil, Joerg/0000-0002-4684-9099; dos Santos Silva, Isabel/0000-0002-6596-8798; Cox, Angela/0000-0002-5138-1099; Yannoukakos, Drakoulis/0000-0001-7509-3510; Giles, Graham/0000-0003-4946-9099; Dobrovic, Alexander/0000-0003-3414-112X; Arias Perez, Jose Ignacio/0000-0003-4500-397X; Garcia-Closas, Montserrat /0000-0003-1033-2650; Dite, Gillian/0000-0002-2448-2548; Bowtell, David/0000-0001-9089-7525; Renner, Stefan/0000-0003-2057-1268; Brenner, Hermann/0000-0002-6129-1572 FU Canadian Institutes of Health Research [CRN-87521]; Cancer Research UK [10124, C1287/A10118, C1287/A12014, C490/A10124, C8197/A10123]; Department of Health [, 03/DHCS/03/G121/51, NF-SI-0512-10122]; Intramural NIH HHS; Medical Research Council [MR/K006215/1]; NCI NIH HHS [CA098758, 5U01CA098216-07, CA116167, CA116201, CA128978, CA132839, CA54281, CA63464, N01CN25403, P30 CA68485, P50 CA116201, R01 CA077398, R01 CA092447, R01 CA77398, R01CA100374, R01CA148667, R01CA64277, R37CA70867, RFA-CA-06-503, U01 CA116167, U01 CA69417, U01 CA69467, U01 CA69638]; Wellcome Trust [090532]; Associazione Italiana per la Ricerca sul Cancro NR 24 TC 4 Z9 5 U1 3 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2014 VL 16 IS 3 AR R51 DI 10.1186/bcr3662 PG 13 WC Oncology SC Oncology GA CA7FT UT WOS:000349083900007 PM 24887515 ER PT J AU De Pascale, G Quraishi, SA AF De Pascale, Gennaro Quraishi, Sadeq A. TI Vitamin D status in critically ill patients: the evidence is now bioavailable! Response SO CRITICAL CARE LA English DT Letter ID CRITICAL ILLNESS; MORTALITY; ASSOCIATION; SEPSIS; CARE C1 [De Pascale, Gennaro; Quraishi, Sadeq A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [De Pascale, Gennaro] Univ Cattolica Sacro Cuore, Dept Intens Care & Anesthesiol, Agostino Gemelli Hosp, I-00168 Rome, Italy. RP De Pascale, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM gdepascale@partners.org NR 9 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2014 VL 18 IS 4 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA CA4MJ UT WOS:000348878200076 ER PT J AU De Pascale, G Quraishi, SA AF De Pascale, Gennaro Quraishi, Sadeq A. TI Vitamin D status in critically ill patients: the evidence is now bioavailable! SO CRITICAL CARE LA English DT Letter C1 [De Pascale, Gennaro; Quraishi, Sadeq A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [De Pascale, Gennaro] Univ Cattolica Sacro Cuore, Agostino Gemelli Hosp, Dept Intens Care & Anesthesiol, I-00168 Rome, Italy. RP De Pascale, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM gdepascale@partners.org NR 0 TC 2 Z9 2 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2014 VL 18 IS 4 AR 449 DI 10.1186/cc13975 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA CA4MJ UT WOS:000348878200075 PM 25043906 ER PT J AU Aguilar, H Urruticoechea, A Halonen, P Kiyotani, K Mushiroda, T Barril, X Serra-Musach, J Islam, A Caizzi, L Di Croce, L Nevedomskaya, E Zwart, W Bostner, J Karlsson, E Tenorio, GP Fornander, T Sgroi, DC Garcia-Mata, R Jansen, MPHM Garca, N Bonifaci, N Climent, F Soler, MT Rodriguez-Vida, A Gil, M Brunet, J Martrat, G Gomez-Baldo, L Extremera, AI Figueras, A Balart, J Clarke, R Burnstein, KL Carlson, KE Katzenellenbogen, JA Vizoso, M Esteller, M Villanueva, A Rodrguez-Pena, AB Bustelo, XR Nakamura, Y Zembutsu, H Stal, O Beijersbergen, RL Pujana, MA AF Aguilar, Helena Urruticoechea, Ander Halonen, Pasi Kiyotani, Kazuma Mushiroda, Taisei Barril, Xavier Serra-Musach, Jordi Islam, Abul Caizzi, Livia Di Croce, Luciano Nevedomskaya, Ekaterina Zwart, Wilbert Bostner, Josefine Karlsson, Elin Tenorio, Gizeh Perez Fornander, Tommy Sgroi, Dennis C. Garcia-Mata, Rafael Jansen, Maurice P. H. M. Garca, Nadia Bonifaci, Nuria Climent, Fina Teresa Soler, Maria Rodriguez-Vida, Alejo Gil, Miguel Brunet, Joan Martrat, Griselda Gomez-Baldo, Laia Extremera, Ana I. Figueras, Agnes Balart, Josep Clarke, Robert Burnstein, Kerry L. Carlson, Kathryn E. Katzenellenbogen, John A. Vizoso, Miguel Esteller, Manel Villanueva, Alberto Rodrguez-Pena, Ana B. Bustelo, Xose R. Nakamura, Yusuke Zembutsu, Hitoshi Stal, Olle Beijersbergen, Roderick L. Angel Pujana, Miguel TI VAV3 mediates resistance to breast cancer endocrine therapy SO BREAST CANCER RESEARCH LA English DT Article ID ESTROGEN-RECEPTOR LIGANDS; PROSTATE-CANCER; ACQUIRED-RESISTANCE; TAMOXIFEN-RESISTANT; ADJUVANT TAMOXIFEN; EXCHANGE FACTOR; RHO GTPASE; CELL-LINES; CHIP-SEQ; EXPRESSION AB Introduction: Endocrine therapies targeting cell proliferation and survival mediated by estrogen receptor alpha (ER alpha) are among the most effective systemic treatments for ER alpha-positive breast cancer. However, most tumors initially responsive to these therapies acquire resistance through mechanisms that involve ER alpha transcriptional regulatory plasticity. Herein we identify VAV3 as a critical component in this process. Methods: A cell-based chemical compound screen was carried out to identify therapeutic strategies against resistance to endocrine therapy. Binding to ER alpha was evaluated by molecular docking analyses, an agonist fluoligand assay and short hairpin (sh)RNA-mediated protein depletion. Microarray analyses were performed to identify altered gene expression. Western blot analysis of signaling and proliferation markers, and shRNA-mediated protein depletion in viability and clonogenic assays, were performed to delineate the role of VAV3. Genetic variation in VAV3 was assessed for association with the response to tamoxifen. Immunohistochemical analyses of VAV3 were carried out to determine its association with therapeutic response and different tumor markers. An analysis of gene expression association with drug sensitivity was carried out to identify a potential therapeutic approach based on differential VAV3 expression. Results: The compound YC 1 was found to comparatively reduce the viability of cell models of acquired resistance. This effect was probably not due to activation of its canonical target (soluble guanylyl cyclase), but instead was likely a result of binding to ER alpha VAV3 was selectively reduced upon exposure to YC-1 or ER alpha depletion, and, accordingly, VAV3 depletion comparatively reduced the viability of cell models of acquired resistance. In the clinical scenario, germline variation in VAV3 was associated with the response to tamoxifen in Japanese breast cancer patients (rs10494071 combined P value = 8.4 x 10(-4)). The allele association combined with gene expression analyses indicated that low VAV3 expression predicts better clinical outcome. Conversely, high nuclear VAV3 expression in tumor cells was associated with poorer endocrine therapy response. Based on VAV3 expression levels and the response to erlotinib in cancer cell lines, targeting EGFR signaling may be a promising therapeutic strategy. Conclusions: This study proposes VAV3 as a biomarker and a rationale for its use as a signaling target to prevent and/or overcome resistance to endocrine therapy in breast cancer. C1 [Aguilar, Helena; Urruticoechea, Ander; Serra-Musach, Jordi; Bonifaci, Nuria; Martrat, Griselda; Gomez-Baldo, Laia; Extremera, Ana I.; Angel Pujana, Miguel] Bellvitge Inst Biomed Res IDIBELL, Catalan Inst Oncol ICO, Translat Res Lab, Breast Canc & Syst Biol Unit, Barcelona 08908, Catalonia, Spain. [Halonen, Pasi; Beijersbergen, Roderick L.] Netherlands Canc Inst, Div Mol Carcinogenesis, Ctr Biomed Genet, NL-1066 CX Amsterdam, Netherlands. [Halonen, Pasi; Beijersbergen, Roderick L.] Netherlands Canc Inst, Canc Genom Ctr, NL-1066 CX Amsterdam, Netherlands. [Kiyotani, Kazuma; Mushiroda, Taisei; Nakamura, Yusuke] RIKEN, Ctr Genom Med, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. [Barril, Xavier] Univ Barcelona, Inst Biomed IBUB, Dept Phys Chem, E-08028 Barcelona, Spain. [Barril, Xavier; Di Croce, Luciano; Esteller, Manel] Catalan Inst Res & Adv Studies ICREA, Barcelona 08010, Catalonia, Spain. [Serra-Musach, Jordi; Brunet, Joan] Hosp Josep Trueta, Girona Biomed Res Inst IDIBGI, ICO, Catalonia 17007, Spain. [Islam, Abul] Univ Dhaka, Dept Genet Engn & Biotechnol, Dhaka 1000, Bangladesh. [Caizzi, Livia; Di Croce, Luciano] Ctr Genom Regulat CRG, Barcelona 08003, Catalonia, Spain. [Caizzi, Livia; Di Croce, Luciano] Univ Pompeu Fabra, Barcelona 08003, Catalonia, Spain. [Nevedomskaya, Ekaterina; Zwart, Wilbert] Netherlands Canc Inst, Dept Mol Pathol, NL-1066 CX Amsterdam, Netherlands. [Bostner, Josefine; Karlsson, Elin; Tenorio, Gizeh Perez; Stal, Olle] Linkoping Univ, Div Oncol, Cty Council Ostergotland, Dept Clin & Expt Med, SE-58185 Linkoping, Sweden. [Fornander, Tommy] Karolinska Univ Hosp, Stockholm S Gen Hosp, Dept Oncol, SE-11883 Stockholm, Sweden. [Sgroi, Dennis C.] Massachusetts Gen Hosp, Mol Pathol Res Unit, Dept Pathol, Boston, MA 02129 USA. [Garcia-Mata, Rafael] Univ N Carolina, Dept Cell Biol & Physiol, Chapel Hill, NC 27599 USA. [Jansen, Maurice P. H. M.] Erasmus Univ, Med Ctr, Dept Med Oncol, Inst Canc, NL-3000 CA Rotterdam, Netherlands. [Garca, Nadia; Figueras, Agnes; Balart, Josep; Villanueva, Alberto] IDIBELL, ICO, Translat Res Lab, Barcelona 08908, Catalonia, Spain. [Climent, Fina; Teresa Soler, Maria] Univ Hosp Bellvitge, IDIBELL, Dept Pathol, Barcelona 08908, Catalonia, Spain. [Rodriguez-Vida, Alejo; Gil, Miguel] IDIBELL, ICO, Breast Canc Unit, Dept Med Oncol, Barcelona 08908, Catalonia, Spain. [Clarke, Robert] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Burnstein, Kerry L.] Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA. [Carlson, Kathryn E.; Katzenellenbogen, John A.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA. [Vizoso, Miguel; Esteller, Manel] IDIBELL, Canc Epigenet & Biol Program PEBC, Barcelona 08908, Catalonia, Spain. [Esteller, Manel] Univ Barcelona, Sch Med, Dept Physiol Sci 2, Barcelona 08908, Catalonia, Spain. [Rodrguez-Pena, Ana B.; Bustelo, Xose R.] Univ Salamanca, CSIC, Canc Res Ctr, Salamanca 37007, Spain. [Nakamura, Yusuke; Zembutsu, Hitoshi] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab,Minato Ku, Tokyo 1088639, Japan. RP Pujana, MA (reprint author), Bellvitge Inst Biomed Res IDIBELL, Catalan Inst Oncol ICO, Translat Res Lab, Breast Canc & Syst Biol Unit, Avda Gran Via 199, Barcelona 08908, Catalonia, Spain. EM miguelangel.pujana@gmail.com RI Barril, Xavier/K-9607-2014; pujana, Miguel Angel/N-3127-2014; Mushiroda, Taisei/E-3022-2010; Di Croce, Luciano/E-7759-2015; Esteller, Manel/L-5956-2014; Kiyotani, Kazuma/E-3206-2010; OI Barril, Xavier/0000-0002-0281-1347; pujana, Miguel Angel/0000-0003-3222-4044; Di Croce, Luciano/0000-0003-3488-6228; Esteller, Manel/0000-0003-4490-6093; Brunet, Joan/0000-0003-1945-3512; Clarke, Robert/0000-0002-9278-0854 FU Eugenio Rodriguez Pascual Foundation; Government of Catalonia [2009-SGR283]; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [R01 DK015556]; Red Cooperative Research Thematic Network on Cancer (RTICC) [12/0036/0002, 12/0036/0008]; Spanish Ministry of Health, Fund for Health Research-Institute of Health Carlos III [11/00951, 12/01528] FX We wish to thank all study participants and their clinicians for their valuable contributions. This work was supported by grants from the Eugenio Rodriguez Pascual Foundation (2012, to MAP), the Government of Catalonia (2009-SGR283, to AV and MAP), the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (R01 DK015556, to JAK), the Red Cooperative Research Thematic Network on Cancer (RTICC) (12/0036/0002 to XRB and 12/0036/0008 to XRB and MAP) and the Spanish Ministry of Health, Fund for Health Research-Institute of Health Carlos III (11/00951 to AU and 12/01528 to MAP). NR 64 TC 6 Z9 6 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2014 VL 16 IS 3 AR UNSP R53 DI 10.1186/bcr3664 PG 16 WC Oncology SC Oncology GA CA7FT UT WOS:000349083900009 PM 24886537 ER PT J AU Agrawal, T Gupta, GK Rai, V Carroll, JD Hamblin, MR AF Agrawal, Tanupriya Gupta, Gaurav K. Rai, Vikrant Carroll, James D. Hamblin, Michael R. TI PRE-CONDITIONING WITH LOW-LEVEL LASER (LIGHT) THERAPY: LIGHT BEFORE THE STORM SO DOSE-RESPONSE LA English DT Article DE Pre-conditioning; Remote Ischemic Pre-conditioning; LLLT; Photobiomodulation; Mitochondria; Reactive Oxygen Species ID SKELETAL-MUSCLE FATIGUE; ISCHEMIA-REPERFUSION INJURY; CEREBRAL PERFUSION-PRESSURE; ENDOTHELIAL GROWTH-FACTOR; KINASE-C ACTIVATION; MYOCARDIAL-INFARCTION; RAT-HEART; IN-VITRO; ISCHEMIA/REPERFUSION INJURY; INFLAMMATORY RESPONSE AB Pre-conditioning by ischemia, hyperthermia, hypothermia, hyperbaric oxygen (and numerous other modalities) is a rapidly growing area of investigation that is used in pathological conditions where tissue damage may be expected. The damage caused by surgery, heart attack, or stroke can be mitigated by pre-treating the local or distant tissue with low levels of a stress-inducing stimulus, that can induce a protective response against subsequent major damage. Low-level laser (light) therapy (LLLT) has been used for nearly 50 years to enhance tissue healing and to relieve pain, inflammation and swelling. The photons are absorbed in cytochrome(c) oxidase (unit four in the mitochondrial respiratory chain), and this enzyme activation increases electron transport, respiration, oxygen consumption and ATP production. A complex signaling cascade is initiated leading to activation of transcription factors and up- and down-regulation of numerous genes. Recently it has become apparent that LLLT can also be effective if delivered to normal cells or tissue before the actual insult or trauma, in a pre-conditioning mode. Muscles are protected, nerves feel less pain, and LLLT can protect against a subsequent heart attack. These examples point the way to wider use of LLLT as a pre-conditioning modality to prevent pain and increase healing after surgical/medical procedures and possibly to increase athletic performance. C1 [Agrawal, Tanupriya; Gupta, Gaurav K.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Agrawal, Tanupriya; Gupta, Gaurav K.; Hamblin, Michael R.] Harvard Univ, Dept Dermatol, Sch Med, Boston, MA 02115 USA. [Gupta, Gaurav K.] Tufts Med Ctr, Dept Pathol & Lab Med, Boston, MA 02111 USA. [Rai, Vikrant] Albert Einstein Coll Med, Wilf Family Cardiovasc Res Inst, Div Cardiol, Dept Med, Bronx, NY 10461 USA. [Carroll, James D.] THOR Photomed Ltd, Chesham HP5 1HQ, England. [Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), BAR414,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Carroll, James/0000-0002-9205-1061; Hamblin, Michael/0000-0001-6431-4605; Rai, Vikrant/0000-0001-6286-2341 FU US NIH [R01AI050875] FX Research in the Hamblin laboratory is supported by US NIH grant R01AI050875. NR 125 TC 17 Z9 17 U1 0 U2 0 PU INT DOSE-RESPONSE SOC PI AMHERST PA UNIV MASSACHUSETTS SPH, MORRILL SCI CTR 1, N344, 639 N PLEASANT ST, AMHERST, MA 01003-9298 USA SN 1559-3258 J9 DOSE-RESPONSE JI Dose-Response PY 2014 VL 12 IS 4 BP 619 EP 649 DI 10.2203/dose-response.14-032.Agrawal PG 31 WC Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging; Toxicology SC Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging; Toxicology GA AX0SN UT WOS:000346662400010 PM 25552961 ER PT J AU Ford, JH Wise, M Krahn, D Oliver, KA Hall, C Sayer, N AF Ford, James H., II Wise, Meg Krahn, Dean Oliver, Karen Anderson Hall, Carmen Sayer, Nina TI Family Care Map: Sustaining family-centered care in Polytrauma Rehabilitation Centers SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE affective commitment to change; barriers; Family Care Map; family-centered care; information; participation; polytrauma; program implementation; strategies; sustainability; traumatic brain injury; Veterans ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN-INJURY; QUALITY IMPROVEMENT; HEALTH; SUSTAINABILITY; VETERANS; FRAMEWORK; SYSTEM; PAIN; IMPLEMENTATION AB The study assessed sustainability of the Family Care Map, a family-centered approach to providing care for Veterans with polytrauma-related injuries, in four Department of Veterans Affairs Polytrauma Rehabilitation Centers. We applied a mixed-methods approach. Staff surveys used standardized measures of sustainability, commitment to change, information, and participation during implementation. Qualitative inquiry assessed Family Care Map implementation and facilitators and barriers to sustainability. Staff sustainability perceptions had a significant positive correlation with affective commitment to change, participation, and information received about the change process. Family Care Map integration into standard practices and use of its concepts with patients and families related to staff perceptions about sustainability. The degree of use and integration of the Family Care Map in traumatic brain injury/polytrauma care varied among the Polytrauma Rehabilitation Centers. Some successful sustainability strategies included integration into daily workflow and organizational culture. Examples of sustainability barriers included staff awareness and use and outdated information. Some practices, such as measuring and documenting the use of the Family Care Map in treatment plans, may not routinely occur. The focus on family-centered care will require further evaluation of organization-, staff-, and innovation-level attributes that influence sustainability of changes designed to improve family-centered care. C1 [Ford, James H., II] Univ Wisconsin, Ctr Hlth Syst Res & Anal, Madison, WI 53726 USA. [Wise, Meg] Univ Wisconsin, Sonderegger Res Ctr, Madison, WI 53726 USA. [Krahn, Dean; Oliver, Karen Anderson] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Krahn, Dean] Univ Wisconsin, Dept Psychiat, Madison, WI 53726 USA. [Hall, Carmen] Metropolitan State Univ, St Paul, MN USA. [Sayer, Nina] Vet Affairs Med Ctr, Minneapolis Dept, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Sayer, Nina] Vet Affairs Med Ctr, Minneapolis Dept, Polytrauma & Blast Related Injuries Qual Enhancem, Minneapolis, MN USA. RP Ford, JH (reprint author), Univ Wisconsin, Ctr Hlth Syst Res & Anal, 610 Walnut St, Madison, WI 53726 USA. EM jhfordii@wisc.edu RI Sayer, Nina/E-3249-2016; OI /0000-0003-3045-2414 FU VA Polytrauma and Blast-Related Injuries (PT/BRI) Quality Enhancement and Research Initiative (QUERI) Locally Initiated Project [QLP 56-002]; National Institute of Drug Abuse [5 R01 DA020832] FX Funding/Support: This material was based on work supported by the VA Polytrauma and Blast-Related Injuries (PT/BRI) Quality Enhancement and Research Initiative (QUERI) Locally Initiated Project (grant QLP 56-002). Dr. Ford's work was also supported in part by the National Institute of Drug Abuse (grant 5 R01 DA020832). NR 40 TC 3 Z9 3 U1 2 U2 4 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2014 VL 51 IS 8 BP 1311 EP 1324 DI 10.1682/JRRD.2014.03.0066 PG 14 WC Rehabilitation SC Rehabilitation GA CA2ZZ UT WOS:000348776400013 PM 25671632 ER PT J AU Kusek, ME Pazos, MA Pirzai, W Hurley, BP AF Kusek, Mark E. Pazos, Michael A. Pirzai, Waheed Hurley, Bryan P. TI In vitro Coculture Assay to Assess Pathogen Induced Neutrophil Transepithelial Migration SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Infection; Issue 83; Cellular Biology; Epithelium; Neutrophils; Pseudomonas aeruginosa; Respiratory Tract Diseases; Neutrophils; epithelial barriers; pathogens; transmigration ID INTESTINAL EPITHELIAL MONOLAYERS; PSEUDOMONAS-AERUGINOSA; SALMONELLA-TYPHIMURIUM; HEPOXILIN A(3); ESCHERICHIA-COLI; PHOSPHOLIPASE A(2); TRANSMIGRATION; CELLS; ATTACHMENT; SECRETION AB Mucosal surfaces serve as protective barriers against pathogenic organisms. Innate immune responses are activated upon sensing pathogen leading to the infiltration of tissues with migrating inflammatory cells, primarily neutrophils. This process has the potential to be destructive to tissues if excessive or held in an unresolved state. Cocultured in vitro models can be utilized to study the unique molecular mechanisms involved in pathogen induced neutrophil trans-epithelial migration. This type of model provides versatility in experimental design with opportunity for controlled manipulation of the pathogen, epithelial barrier, or neutrophil. Pathogenic infection of the apical surface of polarized epithelial monolayers grown on permeable transwell filters instigates physiologically relevant basolateral to apical trans-epithelial migration of neutrophils applied to the basolateral surface. The in vitro model described herein demonstrates the multiple steps necessary for demonstrating neutrophil migration across a polarized lung epithelial monolayer that has been infected with pathogenic P. aeruginosa (PAO1). Seeding and culturing of permeable transwells with human derived lung epithelial cells is described, along with isolation of neutrophils from whole human blood and culturing of PAO1 and nonpathogenic K12 E. coli (MC1000). The emigrational process and quantitative analysis of successfully migrated neutrophils that have been mobilized in response to pathogenic infection is shown with representative data, including positive and negative controls. This in vitro model system can be manipulated and applied to other mucosal surfaces. Inflammatory responses that involve excessive neutrophil infiltration can be destructive to host tissues and can occur in the absence of pathogenic infections. A better understanding of the molecular mechanisms that promote neutrophil trans-epithelial migration through experimental manipulation of the in vitro coculture assay system described herein has significant potential to identify novel therapeutic targets for a range of mucosal infectious as well as inflammatory diseases. C1 [Kusek, Mark E.; Pazos, Michael A.; Hurley, Bryan P.] Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. [Kusek, Mark E.] MGH Children, Dept Pediat Gastroenterol, Boston, MA USA. [Kusek, Mark E.; Pazos, Michael A.; Pirzai, Waheed; Hurley, Bryan P.] Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Boston, MA 02114 USA. RP Hurley, BP (reprint author), Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. EM bphurley@partners.org FU NIH [1 R01 AI095338-01A1] FX This work was supported financially by NIH (1 R01 AI095338-01A1). NR 43 TC 2 Z9 2 U1 0 U2 3 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 JAN PY 2014 IS 83 AR e50823 DI 10.3791/50823 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ9DZ UT WOS:000348513500013 PM 24430378 ER PT S AU Simon, JH AF Simon, Jack H. BE Goodin, DS TI MRI outcomes in the diagnosis and disease course of multiple sclerosis SO MULTIPLE SCLEROSIS AND RELATED DISORDERS SE Handbook of Clinical Neurology LA English DT Article; Book Chapter ID APPEARING WHITE-MATTER; QUANTITATIVE MAGNETIZATION-TRANSFER; CLINICALLY ISOLATED SYNDROMES; RELAPSING-REMITTING MS; SECONDARY PROGRESSIVE MS; PLACEBO-CONTROLLED TRIAL; BLOOD-BRAIN-BARRIER; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; INTRAMUSCULAR INTERFERON BETA-1A; RESONANCE-IMAGING FINDINGS C1 [Simon, Jack H.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Simon, Jack H.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Simon, JH (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Jack.Simon3@va.gov NR 200 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 0072-9752 BN 978-0-444-63309-5; 978-0-444-52001-2 J9 HAND CLINIC PY 2014 VL 122 BP 405 EP 425 PG 21 WC Clinical Neurology SC Neurosciences & Neurology GA BB8LN UT WOS:000346798400020 PM 24507528 ER PT J AU Zanni, MV Kelesidis, T Fitzgerald, ML Lo, J Abbara, S Wai, B Marmarelis, E Hernandez, NJ Yang, OO Currier, JS Grinspoon, SK AF Zanni, Markella V. Kelesidis, Theodoros Fitzgerald, Michael L. Lo, Janet Abbara, Suhny Wai, Bryan Marmarelis, Eleni Hernandez, Nicholas J. Yang, Otto O. Currier, Judith S. Grinspoon, Steven K. TI HDL redox activity is increased in HIV-infected men in association with macrophage activation and non-calcified coronary atherosclerotic plaque SO ANTIVIRAL THERAPY LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; INFLAMMATION; ANGIOGRAPHY; PROGRESSION; COCULTURES; ADULTS AB Background: HIV is associated with atherosclerosis and low high-density lipoprotein (HDL). With inflammation, HDL becomes dysfunctional. We previously showed that proinflammatory HDL has high HDL redox activity (HRA). In this study, we compare HRA in HIV-infected versus non-HIV-infected subjects and relate HRA to indices of macrophage activation and cardiovascular disease risk. Methods: 102 HIV-infected subjects and 41 matched non-HIV controls without clinical cardiovascular disease underwent coronary CT angiography (CTA) and testing for immune/inflammatory biomarkers. The effect of purified HDL from each study subject on the oxidation rate of dihydrorhodamine-123 (DOR) was normalized to the DOR of pooled HDL from healthy subjects. The normalized ratio DOR subject/DOR pooled was used as a measure of HRA, with higher HRA suggesting dysfunctional HDL. Results: HRA was higher in HIV-infected versus non-HIV subjects (1.4 +/- 0.01 versus 1.3 +/- 0.01, P=0.03). In multivariate modelling for HRA among all subjects, HIV status remained positively related to HRA (P=0.02), even after controlling for traditional cardiovascular risk factors, comorbid conditions and immune activation. Among HIV-infected subjects, HRA correlated inversely with HDL (rho=-0.32, P=0.002) and log adiponectin (r=-0.28, P=0.006), and correlated positively with log sCD163 (r=0.24, P=0.02) - a monocyte/macrophage activation marker - and with the percentage of non-calcified coronary atherosclerotic plaque (r=0.29, P=0.03). sCD163 remained significantly associated with HRA in multivariate modelling among HIV-infected subjects (P=0.03). Conclusions: These data demonstrate increased HRA among HIV-infected subjects versus matched non-HIV subjects with comparable HDL levels. In HIV-infected subjects, HRA relates to macrophage activation and to noncalcified coronary atherosclerotic plaque, which may be rupture-prone. Further studies are needed in HIV-infected patients to elucidate the interplay between immune activation, HDL function and CVD risk. Clinical trial registration number: NCT00455793. C1 [Zanni, Markella V.; Lo, Janet; Marmarelis, Eleni; Grinspoon, Steven K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Nutr Metab, Boston, MA 02163 USA. [Kelesidis, Theodoros; Yang, Otto O.; Currier, Judith S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Fitzgerald, Michael L.; Hernandez, Nicholas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit, Boston, MA USA. [Abbara, Suhny; Wai, Bryan] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Yang, Otto O.] AIDS Healthcare Fdn, Los Angeles, CA USA. RP Zanni, MV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Nutr Metab, Boston, MA 02163 USA. EM mzanni@partners.org OI Kelesidis, Theodoros/0000-0002-8463-3811 FU NCATS NIH HHS [8KL2TR000168-05, KL2 TR000168]; NCRR NIH HHS [1 UL1 RR 025758-01, M01 RR001066, M01-RR-01066, UL1 RR025758]; NHLBI NIH HHS [5R01HL095126, K23 HL092792, R01 HL095123, R01 HL095126, R01 HL112661, R01HL095123, R01HL112661]; NIAID NIH HHS [AI056933, AI068634, AI28697, K24 AI056933, P30 AI028697, U01 AI068634, UM1 AI068634]; NIDDK NIH HHS [K24 DK064545, P30 DK040561, P30DK040561] NR 19 TC 4 Z9 4 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2014 VL 19 IS 8 BP 805 EP 811 DI 10.3851/IMP2756 PG 7 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA CA0JM UT WOS:000348604200010 PM 24535655 ER PT J AU Arendt, LM Keller, PJ Skibinski, A Goncalves, K Naber, SP Buchsbaum, RJ Gilmore, H Come, SE Kuperwasser, C AF Arendt, Lisa M. Keller, Patricia J. Skibinski, Adam Goncalves, Kevin Naber, Stephen P. Buchsbaum, Rachel J. Gilmore, Hannah Come, Steven E. Kuperwasser, Charlotte TI Anatomical localization of progenitor cells in human breast tissue reveals enrichment of uncommitted cells within immature lobules SO BREAST CANCER RESEARCH LA English DT Article ID ADULT HUMAN BREAST; EPITHELIAL STEM-CELLS; MAMMARY-GLAND; FUNCTIONAL-CHARACTERIZATION; STEM/PROGENITOR CELLS; MYOEPITHELIAL CELLS; IN-VITRO; CANCER; DIFFERENTIATION; HIERARCHY AB Introduction: Lineage tracing studies in mice have revealed the localization and existence of lineage-restricted mammary epithelial progenitor cells that functionally contribute to expansive growth during puberty and differentiation during pregnancy. However, extensive anatomical differences between mouse and human mammary tissues preclude the direct translation of rodent findings to the human breast. Therefore, here we characterize the mammary progenitor cell hierarchy and identify the anatomic location of progenitor cells within human breast tissues. Methods: Mammary epithelial cells (MECs) were isolated from disease-free reduction mammoplasty tissues and assayed for stem/progenitor activity in vitro and in vivo. MECs were sorted and evaluated for growth on collagen and expression of lineages markers. Breast lobules were microdissected and individually characterized based on lineage markers and steroid receptor expression to identify the anatomic location of progenitor cells. Spanning-tree progression analysis of density-normalized events (SPADE) was used to identify the cellular hierarchy of MECs within lobules from high-dimensional cytometry data. Results: Integrating multiple assays for progenitor activity, we identified the presence of luminal alveolar and basal ductal progenitors. Further, we show that Type I lobules of the human breast were the least mature, demonstrating an unrestricted pattern of expression of luminal and basal lineage markers. Consistent with this, SPADE analysis revealed that immature lobules were enriched for basal progenitor cells, while mature lobules consisted of increased hierarchal complexity of cells within the luminal lineages. Conclusions: These results reveal underlying differences in the human breast epithelial hierarchy and suggest that with increasing glandular maturity, the epithelial hierarchy also becomes more complex. C1 [Arendt, Lisa M.; Keller, Patricia J.; Skibinski, Adam; Goncalves, Kevin; Kuperwasser, Charlotte] Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Dev Mol & Chem Biol Dept, Boston, MA 02111 USA. [Arendt, Lisa M.; Keller, Patricia J.; Skibinski, Adam; Goncalves, Kevin; Kuperwasser, Charlotte] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. [Naber, Stephen P.] Tufts Med Ctr, Dept Pathol, Boston, MA 02111 USA. [Buchsbaum, Rachel J.] Tufts Med Ctr, Dept Med, Boston, MA 02111 USA. [Gilmore, Hannah] UH Case Med Ctr, Dept Pathol Anat, Cleveland, OH 44106 USA. [Come, Steven E.] Beth Israel Deaconess Med Ctr, Dana Farber Harvard Canc Ctr, Breast Med Oncol Program, Boston, MA 02215 USA. [Kuperwasser, Charlotte] Tufts Univ, Sch Med, Dev Mol & Chem Biol Dept, Boston, MA 02111 USA. RP Kuperwasser, C (reprint author), Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Dev Mol & Chem Biol Dept, 136 Harrison Ave, Boston, MA 02111 USA. EM Charlotte.Kuperwasser@tufts.edu FU Breast Cancer Research Foundation; NIH/NICHD [HD073035]; NIH/NCI [CA125554, CA170851]; NCRR [K01-RR021858] FX The authors would like to thank Dr Jerrica Breindel for critically reading the manuscript. This work was supported by grants from the Breast Cancer Research Foundation (CK), the NIH/NICHD HD073035 (CK), the NIH/NCI CA125554 and CA170851 (CK), and the NCRR K01-RR021858 (LMA). NR 43 TC 5 Z9 5 U1 2 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2014 VL 16 IS 5 AR 453 DI 10.1186/s13058-014-0453-3 PG 16 WC Oncology SC Oncology GA CA1II UT WOS:000348665600028 PM 25315014 ER PT J AU Wong, J Tran, LT Magun, EA Magun, BE Wood, LJ AF Wong, John Tran, Lisa T. Magun, Eli A. Magun, Bruce E. Wood, Lisa J. TI Production of IL-1 beta by bone marrow-derived macrophages in response to chemotherapeutic drugs Synergistic effects of doxorubicin and vincristine SO CANCER BIOLOGY & THERAPY LA English DT Article DE inflammasome; cytokines; nilotinib; ponatinib; sorafenib ID ACTIVATED PROTEIN-KINASES; TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; HEALTHY-INDIVIDUALS; CANCER-CHEMOTHERAPY; NLRP3 INFLAMMASOME; HUMAN MONOCYTES; BREAST-CANCER; LUNG-CANCER; MOUSE MODEL AB Cytotoxic chemotherapeutic drugs, especially when used in combination, are widely employed to treat a variety of cancers in patients but often lead to serious symptoms that negatively affect physical functioning and quality of life. There is compelling evidence that implicates cytotoxic chemotherapy-induced inflammation in the etiology of these symptoms. Because IL-1 beta plays a central role as an initiator cytokine in immune responses, we compared doxorubicin, a drug known to induce IL-1 beta production, with ten other commonly prescribed chemotherapeutic drugs in their ability to lead to processing and secretion of IL-1 beta by primary mouse macrophages. Seven of them (melphalan, cisplatin, vincristine, etoposide, paclitaxel, methotrexate, and cytarabine) caused the production of IL-1 beta in cells pretreated with lipopolysaccharide. When delivered in combination with doxorubicin, one of the drugs, vincristine, was also capable of synergistically activating the NLRP3-dependent inflammasome and increasing expression of IL-1 beta, IL-6, and CXCL1. The absence of TNF-alpha and IL-1 signaling caused a partial reduction in the production of mature IL-1 beta. Three small-molecule inhibitors known to suppress activity of kinases situated upstream of mitogen-activated kinases (MAPKs) inhibited the expression of IL-1 beta, IL-6, and CXCL1 when doxorubicin and vincristine were used singly or together, so specific kinase inhibitors may be useful in reducing inflammation in patients receiving chemotherapy. C1 [Wong, John; Tran, Lisa T.; Magun, Bruce E.; Wood, Lisa J.] Massachusetts Gen Hosp, Sch Nursing, Inst Hlth Profess, Boston, MA 02114 USA. [Magun, Eli A.] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA. RP Wood, LJ (reprint author), Massachusetts Gen Hosp, Sch Nursing, Inst Hlth Profess, Boston, MA 02114 USA. EM ljwood@mghihp.edu FU National Institutes of Health [AI105933.5, 1R01NR013171-01A1] FX We thank Dakshina M. Jandhyala for providing the Zak-/- mice. These studies were supported by grants AI105933.5 (to B.E.M.) and 1R01NR013171-01A1 (to L.J.W.) from the National Institutes of Health. NR 56 TC 5 Z9 5 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PY 2014 VL 15 IS 10 BP 1395 EP 1403 DI 10.4161/cbt.29922 PG 9 WC Oncology SC Oncology GA AZ7EL UT WOS:000348381600013 PM 25046000 ER PT J AU Trufyn, J Hill, MD Scott, JN Modi, J Ciura, V Frayne, R Goyal, M Lautner, D Bhayana, D Davenport, WJ Mah, JK Burton, JM Costello, F AF Trufyn, J. Hill, M. D. Scott, J. N. Modi, J. Ciura, V. Frayne, R. Goyal, M. Lautner, D. Bhayana, D. Davenport, W. J. Mah, J. K. Burton, J. M. Costello, F. TI The Prevalence of Incidental Findings in Multiple Sclerosis Patients SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Article ID NEUROIMAGING RESEARCH; BRAIN MRI; ETHICS AB Background: Incidental findings arising from imaging research have important implications for patient safety. Magnetic resonance imaging is widespread in multiple sclerosis (MS) studies and care, yet the prevalence rate of incidental findings in MS is poorly defined. The absence of such reports in the MS literature suggests that such findings may be deemed inappropriate for documentation in research publications, or possibly, not fully reported at all. Objective: We sought to document incidental findings from a study designed to detect features of chronic cerebrospinal venous insufficiency (CCSVI) in MS patients and control subjects. Methods: Magnetic resonance images were obtained as part of a prospective study conducted between October 2010 and September 2012. Patients with MS (relapsing-remitting, primary progressive, secondary progressive), clinically isolated syndromes, and neuromyelitis optica and age/sex-matched healthy controls were included. All images were reviewed by neuro-radiologists for quality-control purposes. Results: Magnetic resonance imaging was successfully obtained in 166 participants (110 patients, 56 controls). Incidental abnormalities (n = 33) were detected in 15% of patients (n = 17) and 27% of controls (n = 15), comprising 19% overall (n = 32). Conclusions: The prevalence of incidental findings from the MS population was not significantly different from the control population. However, the overall prevalence was high and warrants a careful management strategy for future imaging studies. C1 [Trufyn, J.; Hill, M. D.; Scott, J. N.; Frayne, R.; Goyal, M.; Davenport, W. J.; Burton, J. M.; Costello, F.] Univ Calgary, Dept Clin Neurosci, Fac Med, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada. [Hill, M. D.; Scott, J. N.; Modi, J.; Frayne, R.; Goyal, M.] Univ Calgary, Dept Radiol, Fac Med, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada. [Hill, M. D.] Univ Calgary, Dept Community Hlth Serv, Fac Med, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada. [Davenport, W. J.] Univ Calgary, Dept Med Genet, Fac Med, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada. [Costello, F.] Univ Calgary, Dept Surg Ophthalmol, Fac Med, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada. [Lautner, D.; Bhayana, D.] Foothills Med Ctr, Dept Diagnost Imaging, Calgary, AB, Canada. [Frayne, R.] Foothills Med Ctr, Seaman Family MR Res Ctr, Calgary, AB, Canada. [Mah, J. K.] Alberta Childrens Prov Gen Hosp, Dept Pediat, Calgary, AB, Canada. [Ciura, V.] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. RP Costello, F (reprint author), Univ Calgary, Foothills Med Ctr, Dept Clin Neurosci, UCMC Hlth Sci Ctr,Area 3, 3350 Hosp Dr, Calgary, AB T2N 4N1, Canada. EM fiona.costello@albertahealthservices.ca RI Frayne, Richard/F-9347-2012 OI Frayne, Richard/0000-0003-0358-1210 FU Multiple Sclerosis Society of Canada FX This work was supported by the Multiple Sclerosis Society of Canada. NR 18 TC 0 Z9 0 U1 0 U2 2 PU CANADIAN JOURNAL NEUROLOGICAL SCIENCES INC PI CALGARY PA 709-7015 MACLEOD TRAIL SW, CALGARY, AB T2H 2K6, CANADA SN 0317-1671 J9 CAN J NEUROL SCI JI Can. J. Neurol. Sci. PD JAN PY 2014 VL 41 IS 1 BP 49 EP 52 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA AY4WK UT WOS:000347575700010 PM 24384337 ER PT J AU Fellgiebel, A Gartenschlager, M Wildberger, K Scheurich, A Desnick, RJ Sims, K AF Fellgiebel, Andreas Gartenschlaeger, Martin Wildberger, Kerstin Scheurich, Armin Desnick, Robert J. Sims, Katherine TI Enzyme Replacement Therapy Stabilized White Matter Lesion Progression in Fabry Disease SO CEREBROVASCULAR DISEASES LA English DT Article DE Fabry disease; White matter lesions; Enzyme replacement therapy ID MRI; SEGMENTATION; HYPERTROPHY; MANAGEMENT; REVERSAL; TRIAL AB Background: The central nervous system manifestations in Fabry disease (FD) include progressive white matter lesions (WMLs) and stroke. Due to progressive microvascular involvement, men and women with FD over 35 years of age develop WMLs. Moreover, the prevalence of stroke has been estimated to be 12 times higher in FD compared with the general population. Enzyme replacement therapy (ERT) is available and has shown beneficial effects on renal, cardiac, and peripheral nerve function in FD, but the ERT effect on the progression of WMLs, or the reduction in cerebrovascular events, remains unknown. Methods: The WML burden and the effect of agalsidase beta 1 mg/kg biweekly on WML progression were assessed longitudinally in a Phase 4 agalsidase- beta placebo-controlled analysis of untreated and treated FD patients with mild-to-moderate renal involvement (serum creatinine measurements of >= 1.2 mg/dl and < 3.0 mg/dl). The primary end point was the difference in the number of patients with increased WML burden between the agalsidase beta and placebo groups at the end of treatment. The diameters of the WMLs were determined manually using axial flow-attenuated-inversion-recovery-weighted magnetic resonance imaging (MRI) scans taken at baseline and follow-up. Results: MRI scans from 41 FD patients (mean age 43.9, age range 20-68, 3 females; n = 25 on ERT, n = 16 on placebo) were analyzed. WML burden was present in 63% of patients at baseline, increased over a mean of 27 months (range 12-33 months) follow-up, and correlated with left ventricular hypertrophy (LVPW). Patients with previous or recent strokes (n = 11, 39-68 years) showed an increase in the number of WMLs (p = 0.005). A greater proportion of younger patients (<= 50 years) on ERT (n = 18) had stable WML burden compared with younger patients in the placebo group (n = 13): 44% (8 of 18) versus 31% (4 of 13), p = 0.014. The number needed to treat was 8. Conclusions: This FD patient cohort, with mild-to-moderate renal involvement, had a significant WML burden and high inter-individual variability associated with the degree of LVPW but not the degree of kidney dysfunction. These advanced patients with increased LVPW and stroke evidence may have had a higher cerebrovascular risk. The WML burden in patients on ERT was more likely to remain stable, compared with patients on placebo. Thus, ERT may reduce the progression of vascular disease, even in advanced FD patients, suggesting that early treatment may stabilize WML progression and stroke risk. (C) 2014 S. Karger AG, Basel C1 [Fellgiebel, Andreas; Wildberger, Kerstin; Scheurich, Armin] Univ Med Ctr Mainz, Dept Psychiat & Psychotherapy, DE-55131 Mainz, Germany. [Gartenschlaeger, Martin] Univ Med Ctr Mainz, Dept Diagnost & Intervent Radiol, DE-55131 Mainz, Germany. [Desnick, Robert J.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Sims, Katherine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Fellgiebel, A (reprint author), Univ Med Ctr Mainz, Dept Psychiat & Psychotherapy, Untere Zahlbacher Str 8, DE-55131 Mainz, Germany. EM andreas.fellgiebel@unimedizin-mainz.de FU Genzyme-Sanofi; Shire HGT; Genzyme Corp; Amicus FX The ISS was sponsored by Genzyme-Sanofi. A.F. received unrestricted grants and speaker's honoraria from Genzyme-Sanofi and Shire HGT. M.G., K.W. and A.S. report no disclosures. R.J.D. is a consultant for Genzyme Corp, Synageva BioPharma, and GSK, has stock or stock options in Amicus Therapeutics and Synageva BioPharma, has grant support from Genzyme Corp, and receives royalties from Genzyme-Sanofi and Shire HGT. K.S. receives support for ISS research from Genzyme-Sanofi and educational program support from Genzyme-Sanofi, Amicus, and Shire HGT. NR 27 TC 12 Z9 14 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2014 VL 38 IS 6 BP 448 EP 456 DI 10.1159/000369293 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AZ4SE UT WOS:000348212200007 PM 25502511 ER PT J AU Calabrese, JR Sachs, GS Lu, K Debelle, M Laszlovszky, I Durgam, S AF Calabrese, J. R. Sachs, G. S. Lu, K. Debelle, M. Laszlovszky, I. Durgam, S. TI EFFICACY AND SAFETY OF CARIPRAZINE IN PATIENTS WITH ACUTE MANIC OR MIXED EPISODES ASSOCIATED WITH BIPOLAR I DISORDER SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 [Calabrese, J. R.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Sachs, G. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lu, K.; Durgam, S.] Forest Res Inst, Jersey City, NJ USA. [Debelle, M.; Laszlovszky, I.] Gedeon Richter Plc, Med Div, Budapest, Hungary. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 EI 1778-3585 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 2014 VL 29 SU 1 MA EPA-0869 PG 1 WC Psychiatry SC Psychiatry GA AY0IO UT WOS:000347280700670 ER PT J AU Fava, M Freeman, M Williams, JBW Detke, M AF Fava, M. Freeman, M. Williams, J. B. W. Detke, M. TI ARE DIFFERENT METHODS TO REDUCE PLACEBO RESPONSE IN CNS TRIALS MUTUALLY EXCLUSIVE OR HAVE ADDITIVE EFFECTS? SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 [Fava, M.; Freeman, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Williams, J. B. W.] MedAvante, Global Sci, Hamilton, ON 08619, Canada. [Detke, M.] MedAvante, Hamilton, NJ 08619 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 EI 1778-3585 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 2014 VL 29 SU 1 MA EPA-1780 PG 1 WC Psychiatry SC Psychiatry GA AY0IO UT WOS:000347280701477 ER PT J AU Tapp, A Wood, A Kilzieh, N Sylvers, P Rasmussen, DD Raskind, M AF Tapp, A. Wood, A. Kilzieh, N. Sylvers, P. Rasmussen, D. D. Raskind, M. TI OLANZAPINE, CORRECTION OF MELATONIN SUPPRESSION, AND METABOLIC INDICES SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 [Tapp, A.; Wood, A.; Kilzieh, N.; Sylvers, P.] VA Puget Sound Hlth Care Syst, Mental Hlth Res, Tacoma, WA USA. [Rasmussen, D. D.] VA Puget Sound Hlth Care Syst, Res, Seattle, WA USA. [Raskind, M.] VA Puget Sound Hlth Care Syst, Res & Dev, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 EI 1778-3585 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 2014 VL 29 SU 1 MA EPA-0982 PG 1 WC Psychiatry SC Psychiatry GA AY0IO UT WOS:000347280700753 ER PT S AU Hu, CH El Fakhri, G Li, QZ AF Hu, Chenhui El Fakhri, Georges Li, Quanzheng BE Golland, P Hata, N Barillot, C Hornegger, J Howe, R TI Evaluating Structural Symmetry of Weighted Brain Networks via Graph Matching SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2014, PT II SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 17th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) CY SEP 14-18, 2014 CL Massachusetts Inst Technol, Boston, MA SP Harvard Med Sch HO Massachusetts Inst Technol DE network symmetry; weighted brain networks; graph matching; ADHD; rs-fMRI; coactivation network ID INDIVIDUAL-DIFFERENCES; ASYMMETRIES AB We study the symmetry of weighted brain networks to understand the roles of individual brain areas and the redundancy of the brain connectivity. We quantify the structural symmetry of every node pair in the network by isomorphism of the residual graphs of those nodes. The efficacy of the symmetry measure is evaluated on both simulated networks and real data sets. In the resting state fMRI (rs-fMRI) data, we discover that subjects with inattentive type of Attention Deficit Hyperactivity Disorder (ADHD) demonstrate a higher level of network symmetry in contrast to the typically development group, consistent with former findings. Moreover, by comparing the average functional networks of normal subjects during resting state and activation, we obtain a higher symmetry level in the rs-fMRI network when applying median thresholds to the networks. But the symmetry levels of the networks are almost the same when larger thresholds are used, which may imply the invariance of the prominent network symmetry for ordinary people. C1 [Hu, Chenhui; El Fakhri, Georges; Li, Quanzheng] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, NMMI, Boston, MA 02114 USA. RP Hu, CH (reprint author), Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, NMMI, Boston, MA 02114 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-10470-6; 978-3-319-10469-0 J9 LECT NOTES COMPUT SC PY 2014 VL 8674 BP 733 EP 740 PG 8 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BB8WS UT WOS:000347686400091 ER PT J AU Huang, LW Xiao, A Choi, SY Kan, QN Zhou, WB Chacon-Heszele, MF Ryu, YK McKenna, S Zuo, XF Kuruvilla, R Lipschutz, JH AF Huang, Liwei Xiao, An Choi, Soo Young Kan, Quane Zhou, Weibin Chacon-Heszele, Maria F. Ryu, Yun Kyoung McKenna, Sarah Zuo, Xiaofeng Kuruvilla, Rejji Lipschutz, Joshua H. TI Wnt5a Is Necessary for Normal Kidney Development in Zebrafish and Mice SO NEPHRON EXPERIMENTAL NEPHROLOGY LA English DT Article DE Wnt5a; Kidney development; Pronephros; Mesonephros; Metanephros ID PLANAR CELL POLARITY; ROBINOW-SYNDROME; RENAL DEVELOPMENT; PATHWAY; DISEASE; CILIA AB Background: Wnt5a is important for the development of various organs and postnatal cellular function. Little is known, however, about the role of Wnt5a in kidney development, although WNT5A mutations were identified in patients with Robinow syndrome, a genetic disease which includes developmental defects in kidneys. Our goal in this study was to determine the role of Wnt5a in kidney development. Methods: Whole-mount in situ hybridization was used to establish the expression pattern of Wnt5a during kidney development. Zebrafish with wnt5a knockdown and Wnt5a global knockout mice were used to identify kidney phenotypes. Results: In zebrafish, wnt5a knockdown resulted in glomerular cyst formation and dilated renal tubules. In mice, Wnt5a global knockout resulted in pleiotropic, but severe, kidney phenotypes, including agenesis, fused kidney, hydronephrosis and duplex kidney/ureter. Conclusions: Our data demonstrated the important role of Wnt5a in kidney development. Disrupted Wnt5a resulted in kidney cysts in zebrafish and pleiotropic abnormal kidney development in mice. (C) 2014 S. Karger AG, Basel C1 [Huang, Liwei; Xiao, An; Kan, Quane] Eastern Virginia Med Sch, Dept Med, Norfolk, VA 23501 USA. [Ryu, Yun Kyoung; Kuruvilla, Rejji] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Zhou, Weibin] Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA. [Choi, Soo Young; Zuo, Xiaofeng; Lipschutz, Joshua H.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Lipschutz, Joshua H.] Ralph H Johnson Vet Affairs Med Ctr, Dept Med, Charleston, SC USA. [Chacon-Heszele, Maria F.; McKenna, Sarah] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. RP Lipschutz, JH (reprint author), Med Univ S Carolina, Clinical Sci Bldg 829,96 Jonathan Lucas St, Charleston, SC 29425 USA. EM lipschut@musc.edu OI Kuruvilla, Rejji/0000-0002-2851-675X FU Veteran Affair Merit Award; NIH [DK069909, DK047757, DK093625]; University of Pennsylvania Translational Medicine Institute (Pilot Grant); Satellite Healthcare FX This study was funded by Veteran Affair Merit Award to J.H.L, NIH (DK069909 and DK047757) to J.H.L, DK093625 to L.H, Satellite Healthcare (Norman S. Coplon Extramural Research Grant) to J.H.L, and University of Pennsylvania Translational Medicine Institute (Pilot Grant) to J.H.L. NR 23 TC 5 Z9 6 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2129 J9 NEPHRON EXP NEPHROL JI Nephron Exp. Nephrol PY 2014 VL 128 IS 1-2 BP 80 EP 88 DI 10.1159/000368411 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA AZ3KD UT WOS:000348125100009 PM 25412793 ER PT J AU Keuroghlian, AS Shtasel, D Bassuk, EL AF Keuroghlian, Alex S. Shtasel, Derri Bassuk, Ellen L. TI Out on the Street: A Public Health and Policy Agenda for Lesbian, Gay, Bisexual, and Transgender Youth Who Are Homeless SO AMERICAN JOURNAL OF ORTHOPSYCHIATRY LA English DT Article DE LGBT youth; homelessness; HIV risk behaviors; depression; substance use ID SEXUAL RISK-TAKING; SUBSTANCE USE; LOS-ANGELES; POSTTRAUMATIC-STRESS; YOUNG MEN; ADOLESCENTS; SAMPLE; ORIENTATION; RUNAWAY; SYMPTOMS AB A disproportionate number of lesbian, gay, bisexual, and transgender (LGBT) youth experience homelessness each year in the United States. LGBT youth who are homeless have particularly high rates of mental health and substance use problems, suicidal acts, violent victimization, and a range of HIV risk behaviors. Given the intense needs of LGBT youth experiencing homelessness, it is imperative to understand their unique experiences and develop responsive practices and policies. The range and severity of health risks vary across subgroups of all homeless LGBT youth, and because the population is nonhomogeneous, their particular needs must be identified and addressed. Thus, the purpose of this article is to review the causes of homelessness among LGBT youth, discuss the mental health and victimization risks faced by this population, address differences among homeless LGBT subgoups, and recommend effective interventions and best practices. The authors conclude by discussing promising future research and public policy directions. C1 [Keuroghlian, Alex S.; Shtasel, Derri] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Keuroghlian, Alex S.; Shtasel, Derri; Bassuk, Ellen L.] Harvard Univ, Med Sch, Washington, DC 02138 USA. [Bassuk, Ellen L.] Amer Inst Res, Natl Ctr Family Homelessness, Ctr Social Innovat, Washington, DC USA. RP Keuroghlian, AS (reprint author), McLean Hosp Outpatient Clin, 115 Mill St, Belmont, MA 02478 USA. EM akeuroghlian@partners.org FU NIMH NIH HHS [R25 MH094612] NR 44 TC 22 Z9 22 U1 6 U2 24 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0002-9432 EI 1939-0025 J9 AM J ORTHOPSYCHIAT JI Am. J. Orthopsychiatr. PY 2014 VL 84 IS 1 BP 66 EP 72 DI 10.1037/h0098852 PG 7 WC Psychiatry; Social Work SC Psychiatry; Social Work GA AY1SM UT WOS:000347372300009 PM 24826829 ER PT J AU Jia, XF Romero-Ortega, MI Teng, YD AF Jia, Xiaofeng Romero-Ortega, Mario I. Teng, Yang D. TI Peripheral Nerve Regeneration: Mechanism, Cell Biology, and Therapies SO BIOMED RESEARCH INTERNATIONAL LA English DT Editorial Material C1 [Jia, Xiaofeng] Univ Maryland, Sch Med, Dept Neurosurg, Baltimore, MD 21201 USA. [Jia, Xiaofeng] Johns Hopkins Univ, Dept Biomed Engn Phys Med & Rehabil, Baltimore, MD 21205 USA. [Romero-Ortega, Mario I.] Univ Texas Dallas, Dept Bioengn, Richardson, TX 75083 USA. [Romero-Ortega, Mario I.] Univ Texas Dallas, Dept Surg, Richardson, TX 75083 USA. [Teng, Yang D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg,Spaulding Rehabil Hosp, Boston, MA 02115 USA. [Teng, Yang D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Phys Med & Rehabil,Spaulding Rehabil Hosp, Boston, MA 02115 USA. [Teng, Yang D.] VA Boston Healthcare Syst, Boston, MA USA. RP Jia, XF (reprint author), Univ Maryland, Sch Med, Dept Neurosurg, 10 South Pine St,Med Sch Teaching Facil 559 A, Baltimore, MD 21201 USA. EM xjia1@jhmi.edu; mromero@uta.edu; yang_teng@hms.harvard.edu RI Jia, Xiaofeng/B-2145-2008 OI Jia, Xiaofeng/0000-0003-1445-8525 NR 0 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 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 145304 DI 10.1155/2014/145304 PG 2 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AY8TC UT WOS:000347825200001 ER PT J AU Absar, SF Tahir, M Yagi, Y Wilbur, D AF Absar, Syeda Fatima Tahir, Mohammad Yagi, Yukako Wilbur, David TI Whole Slide Imaging Based Digital Pathology Network between Pakistan and USA SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article C1 [Absar, Syeda Fatima] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Tahir, Mohammad] Fed Govt Poly Clin Hosp, Dept Pathol, Islamabad 44000, Pakistan. [Yagi, Yukako; Wilbur, David] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Wilbur, D (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM dwilbur@partners.org NR 1 TC 0 Z9 0 U1 1 U2 1 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 BP 1 EP 2 DI 10.1155/2014/136838 PG 2 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA AX1UA UT WOS:000346730200001 ER PT J AU Tearney, GJ AF Tearney, Guillermo J. TI Microimaging: Seeing the Unseen in Living Patients SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Editorial Material AB Today's gold standard for medical diagnosis is histology of excised biopsies or surgical specimens where tissue is taken out of the body, processed, sectioned, stained, and looked at under a light microscope by a pathologist. There are many limitations of this technique, including the fact that it is inherently invasive, time consuming, costly, and dangerous for some organs. Furthermore, oftentimes the diseased tissue is not readily seen by visual inspection and as a result the tissue is sampled at a random location, which can be highly inaccurate. If we could instead conduct microscopy inside the body, then we could provide tools for screening, targeting biopsies, making primary disease diagnosis, and guiding intervention on the cellular basis. This promise has motivated the development of a new field, termed in vivo microscopy, the goal of which is to obtain microscopic images from living human patients. Two in vivo microscopy technologies, confocal microscopy and optical coherence tomography, are currently available and in clinical use. Upcoming developments, including whole organ microscopy, swallowable microscopy capsules, molecular imaging, and very high resolution microscopic devices, are in the pipeline and will likely revolutionize how disease is diagnosed and how medicine is practiced in the future. C1 [Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tearney, Guillermo J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Tearney, GJ (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM tearney@helix.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 2 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 UNSP 797108 DI 10.1155/2014/797108 PG 1 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA AX6MY UT WOS:000347037400001 ER PT J AU Singh, JA AF Singh, Jasvinder A. TI The impact of gout on patient's lives: a study of African-American and Caucasian men and women with gout SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID NOMINAL GROUP TECHNIQUE; QUALITY-OF-LIFE; GENERAL-PRACTICE; RHEUMATOID-ARTHRITIS; UNITED-STATES; CARE; HEALTH; MANAGEMENT; HYPERURICEMIA; PREVALENCE AB Introduction: The aim of this study was to examine the impact of gout on quality of life (QOL) and study differences by gender and race. Methods: Ten race-and sex-stratified nominal groups were conducted, oversampling for African-Americans and women with gout. Patients presented, discussed, combined and rank-ordered their concerns. Results: A total of 62 patients with mean age 65.1 years, 60% men, 64% African-American, participated in 10 nominal groups: African-American men (n = 23; 3 groups); African-American women (n = 18; 3 groups); Caucasian men (n = 15; 3 groups); and Caucasian women (n = 6; 1 group). The most frequently cited high-ranked concerns among the ten nominal groups were: (1) effect of gout flare on daily activities (n = 10 groups); (2) work disability (n = 8 groups); (3) severe pain (n = 8 groups); (4) joint swelling and tenderness (n = 6 groups); (5) food restrictions (n = 6 groups); (6) medication related issues (n = 6 groups); (7) dependency on family and others (n = 5 groups); (8) emotional Impact (n = 5 groups); (9) interference with sexual function (n = 4 groups); (10) difficulty with shoes (n = 4 groups); and (11) sleep disruption (n = 4 groups). Compared with men, women ranked the following concerns high more often: problems with shoes (n = 4 versus n = 0 groups); dependency (n = 3 versus n = 2 groups); and joint/limb deformity (n = 2 versus n = 0 group). Compared with Caucasians, African-Americans ranked the following concerns high more often: dietary restrictions (n = 6 versus n = 0 groups); severe pain (n = 6 versus n = 2 groups); gout bringing the day to a "halt" (n = 2 versus n = 0 group); effect on emotional health (n = 4 versus n = 1 groups); and the need for canes/crutches during flares (n = 2 versus n = 0 group). Conclusions: Gout has a significant impact on a patient's QOL. Important differences in the impact of gout by gender and race were noted. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Med, Sch Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. EM Jasvinder.md@gmail.com FU Division of Rheumatology at the University of Alabama at Birmingham; Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) [U19 HS021110]; National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) [P50 AR060772, U34 AR062891]; National Institute of Aging (NIA) [U01 AG018947]; National Cancer Institute (NCI) [U10 CA149950]; Patient Centered Outcomes Research Institute (PCORI) [CE-1304-6631] FX I am thankful to Bridgett Alday, Ana Oliviera and Aseem Bharat for contacting patients and providing support for conducting the nominal groups and Mary Elkins for the administrative oversight. I thank Dr Bruce Lambert for his insightful comments on this paper. I thank several colleagues and patients who provided informal input into drafting the question for the nominal groups. This material is the result of work supported by a grant from the Division of Rheumatology at the University of Alabama at Birmingham and the resources and use of facilities at the Birmingham VA Medical Center, Alabama, USA. JAS is also supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) U19 HS021110, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) P50 AR060772 and U34 AR062891, National Institute of Aging (NIA) U01 AG018947, National Cancer Institute (NCI) U10 CA149950, and research contract CE-1304-6631 from Patient Centered Outcomes Research Institute (PCORI). NR 52 TC 10 Z9 12 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2014 VL 16 IS 3 AR R132 DI 10.1186/ar4589 PG 15 WC Rheumatology SC Rheumatology GA AX7EC UT WOS:000347078700027 PM 24961941 ER PT J AU Xu, J Patel, Z Kottyan, L Gatti, RA McCurdy, DK Kaufman, KM Harley, JB AF Xu, Jiadi Patel, Zubin Kottyan, Leah Gatti, Richard A. McCurdy, Deborah K. Kaufman, Kenneth M. Harley, John B. TI DNA repair in lupus SO ARTHRITIS RESEARCH & THERAPY LA English DT Meeting Abstract CT Conference on Lupus - New Targets, New Approaches CY SEP 18-20, 2014 CL Quebec, CANADA C1 [Xu, Jiadi; Patel, Zubin; Kottyan, Leah] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Gatti, Richard A.; McCurdy, Deborah K.] Univ Calif Los Angeles, Los Angeles, CA USA. [Kaufman, Kenneth M.; Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. EM john.harley@cchmc.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2014 VL 16 SU 1 MA A7 PG 1 WC Rheumatology SC Rheumatology GA AX9IK UT WOS:000347216600008 ER PT J AU Tian, LY Sato, T Niwa, K Kawase, M Tanner, ACR Takahashi, N AF Tian, Lingyang Sato, Takuichi Niwa, Kousuke Kawase, Mitsuo Tanner, Anne C. R. Takahashi, Nobuhiro TI Rapid and Sensitive PCR-Dipstick DNA Chromatography for Multiplex Analysis of the Oral Microbiota SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID POLYMERASE-CHAIN-REACTION; REAL-TIME PCR; SINGLE-NUCLEOTIDE POLYMORPHISMS; SURFACE-PLASMON RESONANCE; DENTAL PLAQUE; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; STREPTOCOCCUS-SOBRINUS; CLINICAL MICROBIOLOGY; HEALTHY-SUBJECTS; VISUAL DETECTION AB A complex of species has been associated with dental caries under the ecological hypothesis. This study aimed to develop a rapid, sensitive PCR-dipstick DNA chromatography assay that could be read by eye for multiplex and semiquantitative analysis of plaque bacteria. Parallel oligonucleotides were immobilized on a dipstick strip for multiplex analysis of target DNA sequences of the cariesassociated bacteria, Streptococcus mutans, Streptococcus sobrinus, Scardovia wiggsiae, Actinomyces species, and Veillonella parvula. Streptavidin-coated blue-colored latex microspheres were to generate signal. Target DNA amplicons with an oligonucleotide-tagged terminus and a biotinylated terminus were coupled with latex beads through a streptavidin-biotin interaction and then hybridized with complementary oligonucleotides on the strip. The accumulation of captured latex beads on the test and control lines produced blue bands, enabling visual detection with the naked eye. The PCR-dipstick DNA chromatography detected quantities as low as 100 pg of DNA amplicons and demonstrated 10-to 1000-fold higher sensitivity than PCR-agarose gel electrophoresis, depending on the target bacterial species. Semiquantification of bacteria was performed by obtaining a series of chromatograms using serial 10-fold dilution of PCR-amplified DNA extracted fromdental plaque samples. The assay time was less than 3 h. The semiquantification procedure revealed the relative amounts of each test species in dental plaque samples, indicating that this disposable device has great potential in analysis of microbial composition in the oral cavity and intestinal tract, as well as in point-of-care diagnosis of microbiota-associated diseases. C1 [Tian, Lingyang; Sato, Takuichi; Takahashi, Nobuhiro] Tohoku Univ, Grad Sch Dent, Div Oral Ecol & Biochem, Sendai, Miyagi 9808575, Japan. [Tian, Lingyang] Sichuan Univ, West China Hosp Stomatol, Dept Prosthodont, Chengdu 610041, Peoples R China. [Niwa, Kousuke; Kawase, Mitsuo] Tohoku Univ, Grad Sch Biomed Engn, Sendai, Miyagi 9808579, Japan. [Niwa, Kousuke] NGK Insulators, Corp R&D, Future Technol Management Ctr, Mizuho Ku, Nagoya, Aichi 4678530, Japan. [Tanner, Anne C. R.] Forsyth Inst, Dept Microbiol, Cambridge, MA 02142 USA. RP Sato, T (reprint author), Tohoku Univ, Grad Sch Dent, Div Oral Ecol & Biochem, Sendai, Miyagi 9808575, Japan. EM tak@m.tohoku.ac.jp FU Japan Society for the Promotion of Science [24390511, 25462945, 25463237, 25670777, 25861785, 26462869] FX This study was supported in part by Grants-in-Aid for Scientific Research (24390511, 25462945, 25463237, 25670777, 25861785, and 26462869) from the Japan Society for the Promotion of Science. NR 47 TC 0 Z9 0 U1 3 U2 5 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 180323 DI 10.1155/2014/180323 PG 10 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AY0UF UT WOS:000347311700001 ER PT J AU Pope, C Davis, BH Hays, MM North-Lee, B AF Pope, Charlene Davis, Boyd H. Hays, Mary M. North-Lee, Bertha TI Task at hand habitus: The search for teamwork in the discourse of nurse to nurse shift handoff communication SO INTERNATIONAL JOURNAL OF QUALITATIVE METHODS LA English DT Meeting Abstract C1 [Pope, Charlene; North-Lee, Bertha] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Pope, Charlene] Med Univ S Carolina, Coll Nursing, Charleston, SC USA. [Davis, Boyd H.] Univ N Carolina, Charlotte, NC 28223 USA. [Hays, Mary M.] Univ Alabama, Huntsville, AL USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU UNIV ALBERTA, INT INST QUALITATIVE METHODOLOGY PI EDMONTON PA 5-217, EDMONTON CLINIC HEALTH ACAD, 11405 87 AVENUE, EDMONTON, AB T6G 1C9, CANADA SN 1609-4069 J9 INT J QUAL METH JI Int. J. Qual. Meth. PY 2014 VL 13 BP 458 EP 458 PG 1 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA AX1KD UT WOS:000346705100033 ER PT J AU Azarbal, B Arbit, B Ramaraj, R Kittleson, M Young, A Czer, L Rafiei, M Currier, J Makkar, R Kobashigawa, J AF Azarbal, Babak Arbit, Boris Ramaraj, Radhakrishnan Kittleson, Michelle Young, Amelia Czer, Lawrence Rafiei, Matthew Currier, Jesse Makkar, Raj Kobashigawa, Jon TI Clinical and Angiographic Outcomes with Everolimus Eluting Stents for the Treatment of Cardiac Allograft Vasculopathy SO JOURNAL OF INTERVENTIONAL CARDIOLOGY LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; BARE-METAL STENTS; SINGLE-CENTER EXPERIENCE; ASSOCIATION TASK-FORCE; INTRAVASCULAR ULTRASOUND; ARTERY-DISEASE; INTERNATIONAL SOCIETY; TRANSPLANT VASCULOPATHY; PRACTICE GUIDELINES; AMERICAN-COLLEGE AB Objectives: This study aimed to examine clinical efficacy, safety, and intermediate clinical outcomes with everolimus-eluting stents (EESs) in patients with transplant coronary artery disease (TCAD). Background: TCAD is a major cause of mortality in patients following orthotopic heart transplantation (OHT). Systemic everolimus in OHT patients has been shown to reduce TCAD. The safety and efficacy of an EES, the Xience V, have not been evaluated in this population. Methods: Patients post-OHT with hemodynamically significant CAD who underwent percutaneous coronary intervention (PCI) with EES were included. Participants were maintained on dual antiplatelet therapy for 1-year post-PCI. We examined procedural success, in-hospital and 1-year mortality, stent thrombosis, angiographic restenosis, and myocardial infarction rates. All patients had follow-up angiography 1-year after PCI. Target vessel revascularization (TVR), target lesion revascularization (TLR), in-segment restenosis, target vessel failure (TVF), and lumen late loss were noted. Results: PCI was performed in 34 de novo lesions in 21 patients, and 40 EES were placed. Procedural success rate was 100%. Average stent was 16.5 +/- 5.1mm long and 3.0 +/- 0.6mm in diameter. All patients had angiographic follow-up (409 +/- 201 days). There was no stent thrombosis, deaths, or myocardial infarctions during follow-up. Two patients had focal in-stent restenosis. TLR rate was 5.9% (2/34), and TVR rate was 11.1% (3/27). Quantitative coronary angiography (QCA) showed stenosis diameter to be 19.98 +/- 17.57%. Conclusions: Use of an EES is associated with a low incidence of TVR and TLR in patients with TCAD. Further studies are needed to determine whether PCI with EES changes long-term outcomes. C1 [Azarbal, Babak; Arbit, Boris; Ramaraj, Radhakrishnan; Kittleson, Michelle; Young, Amelia; Czer, Lawrence; Rafiei, Matthew; Makkar, Raj; Kobashigawa, Jon] Cedars Sinai Med Ctr, Inst Heart, Los Angeles, CA 90048 USA. [Currier, Jesse] Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. RP Arbit, B (reprint author), Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. EM boris.arbit@cshs.org NR 33 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0896-4327 EI 1540-8183 J9 J INTERV CARDIOL JI J. Interv. Cardiol. PD JAN PY 2014 VL 27 IS 1 BP 73 EP 79 DI 10.1111/joic.12071 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AX1HE UT WOS:000346697600010 PM 24118198 ER PT J AU Wiecek, E Dakin, SC Bex, P AF Wiecek, Emily Dakin, Steven C. Bex, Peter TI Metamorphopsia and letter recognition SO JOURNAL OF VISION LA English DT Article DE letter recognition; visual acuity; spatial vision; metamorphopsia; clinical vision; macular degeneration ID OPTICAL COHERENCE TOMOGRAPHY; RETINAL-DETACHMENT SURGERY; VISUAL-ACUITY MEASUREMENTS; AGE-RELATED MACULOPATHY; MACULAR HOLE SURGERY; LETTER IDENTIFICATION; FACE RECOGNITION; DEGENERATION; RANIBIZUMAB; VISION AB Acuity is the most commonly used measure of visual function, and reductions in acuity are associated with most eye diseases. Metamorphopsia-a perceived distortion of visual space-is another common symptom of visual impairment and is currently assessed qualitatively using Amsler (1953) charts. In order to quantify the impact of metamorphopsia on acuity, we measured the effect of physical spatial distortion on letter recognition. Following earlier work showing that letter recognition is tuned to specific spatial frequency (SF) channels, we hypothesized that the effect of distortion might depend on the spatial scale of visual distortion just as it depends on the spatial scale of masking noise. Six normally sighted observers completed a 26 alternate forced choice (AFC) Sloan letter identification task at five different viewing distances, and the letters underwent different levels of spatial distortion. Distortion was controlled using spatially band-pass filtered noise that spatially remapped pixel locations. Noise was varied over five spatial frequencies and five magnitudes. Performance was modeled with logistic regression and worsened linearly with increasing distortion magnitude and decreasing letter size. We found that retinal SF affects distortion at midrange frequencies and can be explained with the tuning of a basic contrast sensitivity function, while object-centered distortion SF follows a similar pattern of letter object recognition sensitivity and is tuned to approximately three cycles per letter (CPL). The interaction between letter size and distortion makes acuity an unreliable outcome for metamorphopsia assessment. C1 [Wiecek, Emily; Bex, Peter] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Wiecek, Emily; Bex, Peter] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02138 USA. [Wiecek, Emily; Dakin, Steven C.] UCL, Inst Ophthalmol, London, England. [Dakin, Steven C.] Moorfields Eye Hosp, Biomed Res Ctr, Natl Inst Hlth Res, London, England. [Dakin, Steven C.] Univ Auckland, Dept Optometry & Vis Sci, Auckland 1, New Zealand. [Bex, Peter] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. RP Wiecek, E (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02138 USA. EM emilywiecek@gmail.com OI Dakin, Steven/0000-0002-3548-9104 FU NIH [R01EY019281]; Wellcome Trust FX This work was supported by NIH grant R01EY019281 and Wellcome Trust (SCD). The authors would like to thank Tom Wallis and MiYoung Kwon for their assistance in analysis and interpretation of data. NR 53 TC 3 Z9 3 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2014 VL 14 IS 14 AR 1 DI 10.1167/14.14.1 PG 10 WC Ophthalmology SC Ophthalmology GA AX8TR UT WOS:000347181800001 PM 25453116 ER PT J AU Guancial, EA Bellmunt, J Yeh, S Rosenberg, JE Berman, DM AF Guancial, Elizabeth A. Bellmunt, Joaquim Yeh, Shuyuan Rosenberg, Jonathan E. Berman, David M. TI The evolving understanding of microRNA in bladder cancer SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Review DE MicroRNAs; Urinary bladder neoplasm; Biomarkers ID TUMOR-SUPPRESSOR; MESENCHYMAL TRANSITION; UROTHELIAL CARCINOMAS; CELL-LINES; IN-VITRO; EXPRESSION; TARGETS; METASTASIS; APOPTOSIS; PATHWAYS AB Purpose: Micro ribonucleic acid (miR) expression is altered in urologic malignancies, including bladder cancer (BC). Individual miRs have been shown to modulate multiple signaling pathways that contribute to BC. We reviewed the primary literature on the role of miRs in BC; we provide a general introduction to the processing, regulation, and function of miRs as tumor suppressors and oncogenes and critically evaluate the literature on the implications of altered miR expression in BC. Materials and methods: We searched the English language literature for original and review articles in PubMed from 1993 to March 2013, using the terms "microRNA" and "bladder cancer," "transitional cell carcinoma,- "urothelial carcinoma." This search yielded 133 unique articles with more than 85% of them published within the last 3 years. Results: To date, the majority of miR studies in BC use profiling to describe dynamic changes in miR expression across stage and grade. Generalized down-regulation of miRs, including those that target the fibroblast growth factor 3 pathway, such as miR-145, miR-101, miR-100, and miR-99a, has been observed in low-grade, non muscle invasive BC. In contrast, generalized increased expression of miRs is observed in high-grade, muscle-invasive BC compared with adjacent normal bladder urothelium, including miRs predicted to target p53, such as miR-21 and miR-373. Furthermore, p53 suppresses transcriptional factors that promote mesenchymal differentiation, ZEB-1 and ZEB-2, through regulation of the miR200 family. Conclusions: Aberrations in miR expression identified between non muscle invasive BC and muscle-invasive BC provide insight into the molecular alterations known to distinguish the two parallel pathways of bladder carcinogenesis. The heterogeneity of tumor specimens and research methods limits the reproducibility of changes in miR expression profiles between studies and underscores the importance of in vivo validation in a field that utilizes in silica miR target-prediction models. (C) 2014 Elsevier Inc. All rights reserved. C1 [Guancial, Elizabeth A.; Bellmunt, Joaquim; Rosenberg, Jonathan E.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Guancial, Elizabeth A.] Univ Rochester, Wilmot Canc Ctr, Rochester, NY USA. [Bellmunt, Joaquim] Hosp del Mar, Res Inst IMIM, Barcelona, Spain. [Yeh, Shuyuan] Univ Rochester, Dept Pathol & Urol, George Whipple Lab Canc Res, Rochester, NY USA. [Rosenberg, Jonathan E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Berman, David M.] Queens Univ, Dept Pathol & Mol Med, Kingston, ON, Canada. RP Guancial, EA (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. EM elizabeth_guancial@urmc.rochester.edu OI Rosenberg, Jonathan/0000-0003-2637-4249 FU Bladder Cancer Advocacy Network FX The authors would like to gratefully acknowledge the Bladder Cancer Advocacy Network for supporting this work. NR 66 TC 0 Z9 0 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JAN PY 2014 VL 32 IS 1 DI 10.1016/j.urolonc.2013.04.014 PG 10 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA AX9SW UT WOS:000347243300072 ER PT J AU Rodriguez, D Barrisford, GW Sanchez, A Preston, MA Kreydin, EI Olumi, AF AF Rodriguez, Dayron Barrisford, Glen W. Sanchez, Alejandro Preston, Mark A. Kreydin, Evgeniy I. Olumi, Aria F. TI Primary spermatic cord tumors: Disease characteristics, prognostic factors, and treatment outcomes SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Urologic neoplasms; Spermatic cord tumor; Inguinoscrotal; Paratesticular; Sarcoma; Survival; Prognostic factors; Outcomes ID LYMPH-NODE DISSECTION; PARATESTICULAR SARCOMAS; MALIGNANT-TUMORS; MANAGEMENT; ADULTS; LYMPHADENECTOMY; EXPERIENCE AB Introduction: Experience with management of spermatic cord tumors (SCTs) is uncommon. We utilized a large population-based cancer registry to characterize the demographic, pathological, treatment characteristics, and outcomes of SCTs. Material and methods: The Surveillance, Epidemiology, and End Results database (1973-2007) was queried. Results: From the database, 362 patients were identified with SCT. The annual incidence of SCT was 0.3 cases per million and did not change over tulle. The most common histologic types were liposarcoma (46%), leiomyosarcoma (20%), histiocytoma (13%), and rhabdomyosarcoma (9%). The median age of diagnosis for rhabdomyosarcomas was (26.3 y), whereas for other SCTs, it was (64.7 y) (P < 0.001). On multivariate analysis, a worse outcome was observed with undifferentiated tumor grade, distant disease, positive lymph nodes, and leiomyosarcoma or histiocytoma cell histology. Conclusion: We describe the largest cohort of SCT studied to date. Liposarcoma was most common, while leiomyosarcoma and histiocytoma histologic subtypes were observed to be the most aggressive. Multivariate analysis revealed that tumor grade, stage, histologic type, and lymph node involvement were independently predictive of prognosis. (C) 2014 Elsevier Inc. All rights reserved. C1 [Rodriguez, Dayron; Barrisford, Glen W.; Sanchez, Alejandro; Preston, Mark A.; Kreydin, Evgeniy I.; Olumi, Aria F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02138 USA. RP Olumi, AF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02138 USA. EM olumi.aria@mgh.harvard.edu NR 27 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JAN PY 2014 VL 32 IS 1 DI 10.1016/j.urolonc.2013.08.009 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA AX9SW UT WOS:000347243300110 ER PT J AU Victorson, DE Brucker, PS Bode, RK Eton, DT Talcott, JA Clark, JA Knight, SJ Litwin, MS Moinpour, CM Reeve, BB Aaronson, NK Bennett, CL Herr, HW McGuire, M Shevrin, D McVary, K Cella, D AF Victorson, David E. Brucker, Penny S. Bode, Rita K. Eton, David T. Talcott, James A. Clark, Jack A. Knight, Sara J. Litwin, Mark S. Moinpour, Carol M. Reeve, Bryce B. Aaronson, Neil K. Bennett, Charles L. Herr, Harry W. McGuire, Michael Shevrin, Daniel McVary, Kevin Cella, David TI Ensuring comprehensive assessment of urinary problems in prostate cancer through patient-physician concordance SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Urinary incontinence; Storage (irritative) symptoms; Voiding (obstructive) symptoms; Patient-reported outcomes; Prostate cancer; Health-related quality of life ID QUALITY-OF-LIFE; BEAM RADIATION-THERAPY; RADICAL PROSTATECTOMY; DECISION-MAKING; OUTCOMES; MEN; COMPLICATIONS; EXPERIENCE; INDEX AB Objectives: To examine the concordance between clinicians and men diagnosed with prostate cancer on a clinician-derived pathophysiological classification of the following self-reported urinary complications: storage (irritative), voiding (obstructive), and leakage/incontinence. Materials and methods: Fourteen urology experts classified 37 urinary function questionnaire items into 3 primary conceptual dimensions (e.g., storage [irritative], voiding [obstnictivel and urinary leakage/incontinence) that would best reflect each item's content. In addition, 218 patient participants provided responses to the 37 items. Using classifications by experts to develop the conceptual framework, the structure was tested using confirmatory factor analyses with patient data. Results: Expert consensus was achieved in the classification of 31 out of 37 items. Using the 3-factor conceptual framework and patient data, the fit indices for the overall correlated factor model suggested an acceptable overall model fit. The analyses of the separate domains showed acceptable fit for the storage/irritative domain and the leaking/incontinence domain. The dimensionality of the voiding/obstructive domain was too difficult to estimate. Conclusions: Our analysis found items that conceptually and psychometrically support 2 constructs (leaking/incontinence and storage/irritative). The consistency of this support between the groups suggests a clinical relevance that is useful in treating patients. We have conceptual support for a third hypothesis (voiding/obstructive), although there were too few items to assess this psychometrically. Relative motivating factors of bother and urinary complaints were not addressed and remain an unmet need in this field. (C) 2014 Elsevier Inc. All rights reserved. C1 [Victorson, David E.; Cella, David] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Evanston, IL 60208 USA. [Brucker, Penny S.] Brucker & Associates, Naperville, IL USA. [Bode, Rita K.] Rehabil Inst Chicago, Ctr Rehabil Outcomes Res, Chicago, IL USA. [Eton, David T.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Talcott, James A.] Massachusetts Gen Hosp, Ctr Outcomes Res, Boston, MA 02114 USA. [Clark, Jack A.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Clark, Jack A.] Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Knight, Sara J.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Knight, Sara J.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Litwin, Mark S.] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA 90024 USA. [Litwin, Mark S.] Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA 90024 USA. [Moinpour, Carol M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Reeve, Bryce B.] Univ N Carolina, Dept Hlth Policy & Management, Chapel Hill, NC USA. [Aaronson, Neil K.] Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, Amsterdam, Netherlands. [Bennett, Charles L.] South Carolina Coll Pharm, Dept Clin Pharm & Outcomes Sci, Columbia, SC USA. [Herr, Harry W.] Mem Sloan Kettering Canc Ctr, Dept Urol, New York, NY 10065 USA. [Herr, Harry W.] Weill Cornell Med Coll, New York, NY USA. [McGuire, Michael] NorthShore Univ Hlth Syst, Dept Surg, Evanston, IL USA. [Shevrin, Daniel] NorthShore Univ Hlth Syst, Div Hematol Oncol, Evanston, IL USA. [McVary, Kevin] Northwestern Univ, Feinberg Sch Med, Dept Urol, Evanston, IL 60208 USA. RP Victorson, DE (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Evanston, IL 60208 USA. EM d-victorson@northwestern.edu FU American Cancer Society [RSG-01-221-01-PBP] FX This study was supported from a grant from the American Cancer Society (#RSG-01-221-01-PBP) and designed and conducted by independent investigators from the multiple institutions listed. The contents represent original work and have not been published elsewhere. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the author(s) or upon any organization with which the author(s) is/are associated. NR 30 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JAN PY 2014 VL 32 IS 1 DI 10.1016/j.urolonc.2012.09.006 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA AX9SW UT WOS:000347243300014 ER PT J AU Morrison, FJR Zhang, HB Skentzos, S Shubina, M Bentley-Lewis, R Turchin, A AF Morrison, Fritha J. R. Zhang, Huabing Skentzos, Stephen Shubina, Maria Bentley-Lewis, Rhonda Turchin, Alexander TI Reasons for Discontinuation of Lipid-Lowering Medications in Patients with Chronic Kidney Disease SO CARDIORENAL MEDICINE LA English DT Article DE Medication discontinuation; Chronic kidney disease; Lipid-lowering medications ID ACUTE CORONARY SYNDROMES; GLOMERULAR-FILTRATION-RATE; STATIN THERAPY; MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENTS; BONFERRONI PROCEDURE; ELDERLY PATIENTS; MULTIPLE TESTS; ADHERENCE; OUTCOMES AB Background/Aims: Many patients with chronic kidney disease (CKD) do not receive lipid-lowering therapy despite their high cardiovascular risk. The reasons for this are unknown. Methods: We have conducted a retrospective cohort study of discontinuation of lipid-lowering drugs in patients with CKD stage 3 and higher treated in practices affiliated with two academic medical centers between 2000 and 2010. Information on medication discontinuation and its reasons was obtained from electronic medical records, including natural language processing of electronic notes using previously validated software. Results: Out of 14,034 patients in the study cohort, 10,072 (71.8%) stopped their lipid-lowering drugs at least once, and 2,444 (17.4%) stopped them for at least 1 month. Patients who had a comorbidity associated with higher cardiovascular risk were less likely to stop lipid-lowering drugs. Insurance request was the most common explicitly documented reason for discontinuation, and adverse reactions were the most common reason for long-term discontinuation. In a multivariable analysis, patients were more likely to stop a lipid-lowering drug because of an insurance request if they had government insurance and they were also more likely to stop a lipid-lowering drug because of adverse reactions if they had a history of multiple adverse reactions to other medications. There was no significant relationship between CKD stage and the reason for discontinuation of lipid-lowering drugs. Conclusions: Patients with CKD frequently stop lipid-lowering drugs. Insurance requests and adverse reactions are common reasons for the discontinuation. Further research is needed to ensure appropriate lipid-lowering therapy for these individuals at high cardiovascular risk. (C) 2014 S. Karger AG, Basel C1 [Morrison, Fritha J. R.] Tulane Univ, New Orleans, LA 70118 USA. [Skentzos, Stephen] Stanford Univ, Stanford, CA 94305 USA. [Shubina, Maria; Turchin, Alexander] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bentley-Lewis, Rhonda] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zhang, Huabing] Beijing Union Med Coll Hosp, Beijing, Peoples R China. RP Turchin, A (reprint author), Brigham & Womens Hosp, Div Endocrinol, 221 Longwood Ave, Boston, MA 02115 USA. EM aturchin@partners.org OI Zhang, Huabing/0000-0001-6259-7584 FU Merck; Sharp; Dohme FX This work was supported in part by an investigator-initiated grant from Merck, Sharp, and Dohme. NR 38 TC 3 Z9 3 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1664-3828 EI 1664-5502 J9 CARDIORENAL MED JI CardioRenal Med. PY 2014 VL 4 IS 3-4 BP 225 EP 233 DI 10.1159/000368914 PG 9 WC Cardiac & Cardiovascular Systems; Urology & Nephrology SC Cardiovascular System & Cardiology; Urology & Nephrology GA AX4EN UT WOS:000346886700010 PM 25737687 ER PT J AU Li, W Xu, H Xiao, TF Cong, L Love, MI Zhang, F Irizarry, RA Liu, JS Brown, M Liu, XS AF Li, Wei Xu, Han Xiao, Tengfei Cong, Le Love, Michael I. Zhang, Feng Irizarry, Rafael A. Liu, Jun S. Brown, Myles Liu, X. Shirley TI MAGeCK enables robust identification of essential genes from genome-scale CRISPR/Cas9 knockout screens SO GENOME BIOLOGY LA English DT Article ID ZINC-FINGER PROTEIN; SEQUENCE COUNT DATA; HUMAN-CELLS; DIFFERENTIAL EXPRESSION; COLORECTAL CANCERS; MELANOMA-CELLS; RAF INHIBITION; CAS9; SPECIFICITY; CARCINOMAS AB We propose the Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout (MAGeCK) method for prioritizing single-guide RNAs, genes and pathways in genome-scale CRISPR/Cas9 knockout screens. MAGeCK demonstrates better performance compared with existing methods, identifies both positively- and negatively-selected genes simultaneously, and reports robust results across different experimental conditions. Using public datasets, MAGeCK identified novel essential genes and pathways, including EGFR in vemurafenib treated A375 cells harboring a BRAF mutation. MAGeCK also detected cell-type specific essential genes including BCR and ABL1 in the KBM7 cells bearing a BCR-ABL fusion, and IGF1R in the HL-60 cells, which depends on the insulin signaling pathway for proliferation. C1 [Li, Wei; Xu, Han; Love, Michael I.; Irizarry, Rafael A.; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Li, Wei; Xu, Han; Xiao, Tengfei; Brown, Myles; Liu, X. Shirley] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. [Xiao, Tengfei; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02215 USA. [Cong, Le; Zhang, Feng] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Cong, Le; Zhang, Feng] MIT, McGovern Inst Brain Res, Dept Brain & Cognit Sci, Dept Biol Engn, Cambridge, MA 02139 USA. [Liu, Jun S.] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. [Brown, Myles] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Liu, XS (reprint author), Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. EM li.david.wei@gmail.com; hanxu@jimmy.harvard.edu; xtfmail@gmail.com; congle.thu@gmail.com; michaelisaiahlove@gmail.com; zhangf@mit.edu; rairizarry@gmail.com; jliu1600@gmail.com; myles_brown@dfci.harvard.edu; xsliu@jimmy.harvard.edu RI Cong, Le/M-9981-2013 OI Cong, Le/0000-0003-4725-8714 FU NIH [R01 GM099409]; Claudia Adams Barr Award in Innovative Basic Cancer Research from the Dana-Farber Cancer Institute FX The authors would like to thank Drs. Tim Wang, Eric Lander, David Sabatini, Ophir Shalem, Neville Sanjana, Graham McVicker and Clifford Meyer for providing the datasets and helpful discussions. This project was supported by the NIH R01 GM099409 (to X.S.L.), and the Claudia Adams Barr Award in Innovative Basic Cancer Research from the Dana-Farber Cancer Institute. NR 36 TC 26 Z9 29 U1 4 U2 25 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 554 DI 10.1186/s13059-014-0554-4 PG 24 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AW9XX UT WOS:000346609500026 PM 25476604 ER PT J AU Serper, M Forde, KA Kaplan, DE AF Serper, Marina Forde, Kimberly A. Kaplan, David E. TI Serologic Testing Rates among US Veterans with Hepatitis B 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 [Kaplan, David E.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Serper, Marina; Forde, Kimberly A.; Kaplan, David E.] Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 68 BP 230A EP 231A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483801002 ER PT J AU Portelius, E Dean, RA Andreasson, U Mattsson, N Westerlund, A Olsson, M Demattos, RB Racke, MM Zetterberg, H May, PC Blennow, K AF Portelius, Erik Dean, Robert A. Andreasson, Ulf Mattsson, Niklas Westerlund, Anni Olsson, Maria Demattos, Ronald Bradley Racke, Margaret M. Zetterberg, Henrik May, Patrick C. Blennow, Kaj TI beta-site amyloid precursor protein-cleaving enzyme 1(BACE1) inhibitor treatment induces A beta 5-X peptides through alternative amyloid precursor protein cleavage SO ALZHEIMERS RESEARCH & THERAPY LA English DT Article ID GAMMA-SECRETASE INHIBITION; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; ISOFORM PATTERN; QUANTIFICATION; DEPOSITION; CSF AB Introduction: The beta-secretase enzyme, beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1), cleaves amyloid precursor protein (APP) in the first step in beta-amyloid (A beta) peptide production. Thus, BACE1 is a key target for candidate disease-modifying treatment of Alzheimer's disease. In a previous exploratory A beta biomarker study, we found that BACE1 inhibitor treatment resulted in decreased levels of A beta 1-34 together with increased A beta 5-40, suggesting that these A beta species may be novel pharmacodynamic biomarkers in clinical trials. We have now examined whether the same holds true in humans. Methods: In an investigator-blind, placebo-controlled and randomized study, healthy subjects (n = 18) were randomly assigned to receive a single dose of 30 mg of LY2811376 (n = 6), 90 mg of LY2811376 (n = 6), or placebo (n = 6). We used hybrid immunoaffinity-mass spectrometry (HI-MS) and enzyme-linked immunosorbent assays to monitor a variety of A beta peptides. Results: Here, we demonstrate dose-dependent changes in cerebrospinal fluid (CSF) A beta 1-34, A beta 5-40 and A beta 5-X after treatment with the BACE1-inhibitor LY2811376. A beta 5-40 and A beta 5-X increased dose-dependently, as reflected by two independent methods, while A beta 1-34 dose-dependently decreased. Conclusion: Using HI-MS for the first time in a study where subjects have been treated with a BACE inhibitor, we confirm that CSF A beta 1-34 may be useful in clinical trials on BACE1 inhibitors to monitor target engagement. Since it is less hydrophobic than longer A beta species, it is less susceptible to preanalytical confounding factors and may thus be a more stable marker. By independent measurement techniques, we also show that BACE1 inhibition in humans is associated with APP-processing into N-terminally truncated A beta peptides via a BACE1-independent pathway. C1 [Portelius, Erik; Andreasson, Ulf; Mattsson, Niklas; Westerlund, Anni; Olsson, Maria; Zetterberg, Henrik; Blennow, Kaj] Univ Gothenburg, Sahlgrenska Acad, Dept Psychiat & Neurochem, Clin Neurochem Lab,Inst Neurosci & Phys, S-43180 Molndal, Sweden. [Dean, Robert A.; Demattos, Ronald Bradley; Racke, Margaret M.; May, Patrick C.] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Mattsson, Niklas] Univ Calif San Francisco, Ctr Imaging Neurodegenerat Dis, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Zetterberg, Henrik] UCL Inst Neurol, London WC1N 3BG, England. RP Portelius, E (reprint author), Univ Gothenburg, Sahlgrenska Acad, Dept Psychiat & Neurochem, Clin Neurochem Lab,Inst Neurosci & Phys, S-43180 Molndal, Sweden. EM erik.portelius@neuro.gu.se FU Lundbeck Foundation; Swedish Research Council; Swedish State Support for Clinical Research; Stiftelsen Psykiatriska Forskningsfonden; Wolfson Foundation; Stiftelsen Gamla Tjanarinnor; Magn. Bergvalls Stiftelse; Gun och Bertil Stohnes Stiftelse; Uppsala Universitets Medicinska Fakultet stiftelse for psykiatrisk och neurologisk forskning; Swedish Brain Fund; Alzheimer Foundation, Sweden; Dementia Association, Sweden; Eli Lilly FX The study was supported by the Lundbeck Foundation, the Swedish Research Council, Swedish State Support for Clinical Research, Stiftelsen Psykiatriska Forskningsfonden, the Wolfson Foundation, Stiftelsen Gamla Tjanarinnor, Magn. Bergvalls Stiftelse, Gun och Bertil Stohnes Stiftelse, Uppsala Universitets Medicinska Fakultet stiftelse for psykiatrisk och neurologisk forskning, the Swedish Brain Fund, the Alzheimer Foundation, Sweden, the Dementia Association, Sweden, and Eli Lilly and Company. NR 28 TC 8 Z9 8 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-9193 J9 ALZHEIMERS RES THER JI Alzheimers Res. Ther. PY 2014 VL 6 IS 9 AR 75 DI 10.1186/s13195-014-0075-0 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AW6CS UT WOS:000346357700006 PM 25404952 ER PT J AU Garcia, C AF Garcia, Christopher TI The Importance of User Interface and User Experience in the Adoption of Whole Slide Images for Clinical Use SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Garcia, C (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM cgarcia14@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 1 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 836176 DI 10.1155/2014/836176 PG 1 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA AW5HZ UT WOS:000346307800001 ER PT J AU Singhal, V Eguiguren, MDL Eisenbach, L Clarke, H Slattery, M Eddy, K Ackerman, KE Misra, M AF Singhal, Vibha Eguiguren, Maria de Lourdes Eisenbach, Lindsey Clarke, Hannah Slattery, Meghan Eddy, Kamryn Ackerman, Kathryn E. Misra, Madhusmita TI Body Composition, Hemodynamic, and Biochemical Parameters of Young Female Normal-Weight Oligo-Amenorrheic and Eumenorrheic Athletes and Nonathletes SO ANNALS OF NUTRITION AND METABOLISM LA English DT Article DE Athletes; Adolescents; Bone density; Body composition; Hormones; Liver function tests; Heart rate; Blood pressure; Hematological tests ID ANOREXIA-NERVOSA; BLOOD-PRESSURE; ADOLESCENT GIRLS; RISK-FACTORS; HEART-RATE; WOMEN; BONE; FAT; PREVALENCE; DEFICIENCY AB Aims: Low-weight hypogonadal conditions such as anorexia nervosa are associated with marked changes in body composition, hemodynamic and hematological parameters, and liver enzymes. The impact of athletic activity in normal- weight adolescents with/without amenorrhea on these parameters has not been assessed. Our aim was to examine these parameters in normal-weight athletes and nonathletes and determine any associations with body composition, oligo-amenorrhea, and exercise intensity. Methods: We assessed vital signs, complete blood counts, liver enzymes, and regional body composition in 43 oligo-amenorrheic athletes (OAA), 24 eumenorrheic athletes (EA), and 23 nonathletes aged 14-21 years. Results: The BMI was lower in OAA than in EA. Systolic and pulse pressure and temperature were lowest in OAA. Blood counts did not differ among groups. Aspartate aminotransferase (AST) was higher in both groups of athletes, while alanine aminotransferase (ALT) was higher in OAA than in EA and nonathletes. Total and regional fat were lower in OAA than in other groups, and these factors were associated positively with heart rate and inversely with liver enzymes. Conclusions: Athletic activity is associated with higher AST levels, whereas menstrual dysfunction is associated with lower total and regional fat and higher ALT levels. Higher liver enzymes are associated with reductions in total and regional fat. (C) 2014 S. Karger AG, Basel C1 [Singhal, Vibha; Eguiguren, Maria de Lourdes; Eisenbach, Lindsey; Clarke, Hannah; Slattery, Meghan; Ackerman, Kathryn E.; Misra, Madhusmita] Neuroendocrine Unit, Boston, MA USA. [Eddy, Kamryn] Massachusetts Gen Hosp, Harris Ctr, Boston, MA 02114 USA. [Singhal, Vibha; Eguiguren, Maria de Lourdes; Eisenbach, Lindsey; Clarke, Hannah; Slattery, Meghan; Ackerman, Kathryn E.; Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Singhal, Vibha; Misra, Madhusmita] Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. [Ackerman, Kathryn E.] Boston Childrens Hosp, Div Sports Med, Boston, MA USA. RP Singhal, V (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457, Boston, MA 02114 USA. EM vsinghal1@partners.org FU NIH [1R01 HD060827, K24 HD07184, 5UL1 RR025758] FX This work was supported by NIH grants 1R01 HD060827, K24 HD07184, and 5UL1 RR025758. NR 42 TC 0 Z9 0 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 EI 1421-9697 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2014 VL 65 IS 4 BP 264 EP 271 DI 10.1159/000366024 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA AW4PM UT WOS:000346263200004 PM 25376841 ER PT J AU van Leyen, K Holman, TR Maloney, DJ AF van Leyen, Klaus Holman, Theodore R. Maloney, David J. TI The potential of 12/15-lipoxygenase inhibitors in stroke therapy SO FUTURE MEDICINAL CHEMISTRY LA English DT Article DE edema; eicosanoid; hemorrhage; ischemia; lipoxygenase; oxidative stress; stroke; tissue plasminogen activator ID SPONGE-DERIVED TERPENOIDS; SELECTIVE INHIBITORS; MAMMALIAN 15-LIPOXYGENASE; LIPOXYGENASE INHIBITORS; DISCOVERY; 15-HUMAN; 12-HUMAN C1 [van Leyen, Klaus] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA 02129 USA. [Holman, Theodore R.] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA. [Maloney, David J.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. RP van Leyen, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA 02129 USA. EM klaus_vanleyen@hms.harvard.edu FU US NIH [R01NS081180, R21NS087165] FX Financial support through the US NIH (R01NS081180 to TR Holman and R21NS087165 to K van Leyen) is gratefully acknowledged. Patents for LOXBlock-1 and for ML351 have been applied for. 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 20 TC 1 Z9 1 U1 1 U2 3 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1756-8919 EI 1756-8927 J9 FUTURE MED CHEM JI Future Med. Chem. PY 2014 VL 6 IS 17 BP 1853 EP 1855 DI 10.4155/fmc.14.129 PG 3 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AW5TS UT WOS:000346337300002 PM 25495979 ER PT J AU Herman, JD Rice, DP Ribacke, U Silterra, J Deik, AA Moss, EL Broadbent, KM Neafsey, DE Desai, MM Clish, CB Mazitschek, R Wirth, DF AF Herman, Jonathan D. Rice, Daniel P. Ribacke, Ulf Silterra, Jacob Deik, Amy A. Moss, Eli L. Broadbent, Kate M. Neafsey, Daniel E. Desai, Michael M. Clish, Clary B. Mazitschek, Ralph Wirth, Dyann F. TI A genomic and evolutionary approach reveals non-genetic drug resistance in malaria SO GENOME BIOLOGY LA English DT Article ID RED-BLOOD-CELLS; PARASITE PLASMODIUM-FALCIPARUM; TRANSFER-RNA SYNTHETASE; AMINO-ACID STARVATION; ESCHERICHIA-COLI; COMPENSATORY MUTATIONS; ANTIBIOTIC-RESISTANCE; PROLINE TRANSPORTER; PERMEATION PATHWAYS; MOLECULAR-CLONING AB Background: Drug resistance remains a major public health challenge for malaria treatment and eradication. Individual loci associated with drug resistance to many antimalarials have been identified, but their epistasis with other resistance mechanisms has not yet been elucidated. Results: We previously described two mutations in the cytoplasmic prolyl-tRNA synthetase (cPRS) gene that confer resistance to halofuginone. We describe here the evolutionary trajectory of halofuginone resistance of two independent drug resistance selections in Plasmodium falciparum. Using this novel methodology, we discover an unexpected non-genetic drug resistance mechanism that P. falciparum utilizes before genetic modification of the cPRS. P. falciparum first upregulates its proline amino acid homeostasis in response to halofuginone pressure. We show that this non-genetic adaptation to halofuginone is not likely mediated by differential RNA expression and precedes mutation or amplification of the cPRS gene. By tracking the evolution of the two drug resistance selections with whole genome sequencing, we further demonstrate that the cPRS locus accounts for the majority of genetic adaptation to halofuginone in P. falciparum. We further validate that copy-number variations at the cPRS locus also contribute to halofuginone resistance. Conclusions: We provide a three-step model for multi-locus evolution of halofuginone drug resistance in P. falciparum. Informed by genomic approaches, our results provide the first comprehensive view of the evolutionary trajectory malaria parasites take to achieve drug resistance. Our understanding of the multiple genetic and non-genetic mechanisms of drug resistance informs how we will design and pair future anti-malarials for clinical use. C1 [Herman, Jonathan D.; Ribacke, Ulf; Neafsey, Daniel E.; Mazitschek, Ralph; Wirth, Dyann F.] Harvard Univ, Sch Med, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Herman, Jonathan D.; Silterra, Jacob; Deik, Amy A.; Moss, Eli L.; Broadbent, Kate M.; Neafsey, Daniel E.; Clish, Clary B.; Mazitschek, Ralph; Wirth, Dyann F.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Herman, Jonathan D.] Biol & Biomed Sci, Boston, MA 02115 USA. [Herman, Jonathan D.] Harvard MIT Div Hlth Sci & Technol, Boston, MA 02115 USA. [Herman, Jonathan D.] Harvard Univ, Sch Med, Harvard MIT MD PhD Program, Boston, MA 02115 USA. [Rice, Daniel P.; Desai, Michael M.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. [Rice, Daniel P.; Desai, Michael M.] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA. [Ribacke, Ulf] Uppsala Univ, Dept Cell & Mol Biol, S-75105 Uppsala, Sweden. [Mazitschek, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Wirth, DF (reprint author), Harvard Univ, Sch Med, Dept Immunol & Infect Dis, Boston, MA 02115 USA. EM dfwirth@hsph.harvard.edu FU Gates Foundation; Exxon Mobil Foundation; NSF; National Institute of Health [AI084031, T32 GM007306-39, GM104239] FX We gratefully acknowledge financial support for this work by the Gates Foundation (DFW and RM), Exxon Mobil Foundation, NSF Graduate Research Fellowship (DPR), and the National Institute of Health (DFW - AI084031, JDH - T32 GM007306-39, DPR and MMD - GM104239). NR 52 TC 6 Z9 6 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2014 VL 15 IS 11 AR 511 DI 10.1186/s13059-014-0511-2 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AW9XA UT WOS:000346607300012 PM 25395010 ER PT J AU Love, MI Huber, W Anders, S AF Love, Michael I. Huber, Wolfgang Anders, Simon TI Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 SO GENOME BIOLOGY LA English DT Article ID IDENTIFYING DIFFERENTIAL EXPRESSION; SEQUENCE COUNT DATA; BIOLOGICAL VARIATION; MICROARRAY DATA; INFERENCE; CLASSIFICATION; NORMALIZATION; VARIABILITY; REGRESSION; POWERFUL AB In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html. C1 [Love, Michael I.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Love, Michael I.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Love, Michael I.; Huber, Wolfgang; Anders, Simon] European Mol Biol Lab, Genome Biol Unit, D-69117 Heidelberg, Germany. [Love, Michael I.] Max Planck Inst Mol Genet, Dept Computat Mol Biol, D-14195 Berlin, Germany. RP Anders, S (reprint author), European Mol Biol Lab, Genome Biol Unit, Meyerhofstr 1, D-69117 Heidelberg, Germany. EM mlove@jimmy.harvard.edu; huber@embl.de; sanders@fs.tum.de RI Anders, Simon/D-4087-2011 OI Anders, Simon/0000-0003-4868-1805 FU International Max Planck Research School for Computational Biology and Scientific Computing; National Institutes of Health [5T32CA009337-33]; European Union's 7th Framework Programme (Health) via Project Radiant FX The authors thank all users of DESeq and DESeq2 who provided valuable feedback. We thank Judith Zaugg for helpful comments on the manuscript. ML acknowledges funding via a stipend from the International Max Planck Research School for Computational Biology and Scientific Computing and a grant from the National Institutes of Health (5T32CA009337-33). WH and SA acknowledge funding from the European Union's 7th Framework Programme (Health) via Project Radiant. We thank an anonymous reviewer for raising the question of estimation biases in the dispersion-mean trend fitting. NR 64 TC 340 Z9 344 U1 41 U2 166 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 550 DI 10.1186/s13059-014-0550-8 PG 38 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AW9XX UT WOS:000346609500022 PM 25516281 ER PT J AU Prandi, D Baca, SC Romanel, A Barbieri, CE Mosquera, JM Fontugne, J Beltran, H Sboner, A Garraway, LA Rubin, MA Demichelis, F AF Prandi, Davide Baca, Sylvan C. Romanel, Alessandro Barbieri, Christopher E. Mosquera, Juan-Miguel Fontugne, Jacqueline Beltran, Himisha Sboner, Andrea Garraway, Levi A. Rubin, Mark A. Demichelis, Francesca TI Unraveling the clonal hierarchy of somatic genomic aberrations SO GENOME BIOLOGY LA English DT Article ID COPY-NUMBER ALTERATIONS; PROSTATE-CANCER; TUMOR TYPES; STATISTICAL APPROACH; LUNG ADENOCARCINOMA; SEQUENCING DATA; MUTATIONS; GENES; IDENTIFICATION; HETEROGENEITY AB Defining the chronology of molecular alterations may identify milestones in carcinogenesis. To unravel the temporal evolution of aberrations from clinical tumors, we developed CLONET, which upon estimation of tumor admixture and ploidy infers the clonal hierarchy of genomic aberrations. Comparative analysis across 100 sequenced genomes from prostate, melanoma, and lung cancers established diverse evolutionary hierarchies, demonstrating the early disruption of tumor-specific pathways. The analyses highlight the diversity of clonal evolution within and across tumor types that might be informative for risk stratification and patient selection for targeted therapies. CLONET addresses heterogeneous clinical samples seen in the setting of precision medicine. C1 [Prandi, Davide; Romanel, Alessandro; Demichelis, Francesca] Univ Trento, Ctr Integrat Biol, I-38123 Povo, Italy. [Baca, Sylvan C.; Garraway, Levi A.] Broad Inst MIT & Harvard, Cambridge, MA 02141 USA. [Baca, Sylvan C.; Garraway, Levi A.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Baca, Sylvan C.; Garraway, Levi A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Barbieri, Christopher E.; Rubin, Mark A.] Cornell Univ, Weill Med Coll, Dept Urol, New York, NY 10065 USA. [Barbieri, Christopher E.; Mosquera, Juan-Miguel; Fontugne, Jacqueline; Sboner, Andrea; Rubin, Mark A.] Cornell Univ, Weill Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA. [Beltran, Himisha] Cornell Univ, Weill Med Coll, Dept Med, Div Hematol & Oncol, New York, NY 10065 USA. [Barbieri, Christopher E.; Mosquera, Juan-Miguel; Beltran, Himisha; Sboner, Andrea; Rubin, Mark A.; Demichelis, Francesca] Cornell Univ, Weill Med Coll, Inst Precis Med, New York, NY 10065 USA. [Barbieri, Christopher E.; Mosquera, Juan-Miguel; Beltran, Himisha; Sboner, Andrea; Rubin, Mark A.; Demichelis, Francesca] New York Presbyterian Hosp, New York, NY 10065 USA. [Sboner, Andrea; Demichelis, Francesca] Cornell Univ, Weill Med Coll, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsa, New York, NY 10065 USA. RP Demichelis, F (reprint author), Univ Trento, Ctr Integrat Biol, I-38123 Povo, Italy. EM demichelis@science.unitn.it OI Prandi, Davide/0000-0001-9885-6074; Rubin, Mark/0000-0002-8321-9950; Romanel, Alessandro/0000-0003-4855-8620 FU US Department of Defense Synergy Award [PC101020]; US National Cancer Institute [2R01CA125612-05A1]; Prostate Cancer Foundation; Early Detection Research Network US NCI [CA111275]; Translational Research Program at WCMC, Department of Pathology and Laboratory Medicine FX This work was supported by the following grants: US Department of Defense Synergy Awards (PC101020 to FD, LAG, and MAR), US National Cancer Institute (2R01CA125612-05A1 to MAR and FD), the Prostate Cancer Foundation, the Prostate Cancer Foundation Young Investigator Award (CEB), Early Detection Research Network US NCI CA111275 (MAR, JMM). Tissue-based work was supported in part by the Translational Research Program at WCMC, Department of Pathology and Laboratory Medicine. NR 46 TC 19 Z9 20 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2014 VL 15 IS 8 AR 439 DI 10.1186/s13059-014-0439-6 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AW9UU UT WOS:000346604100020 PM 25160065 ER PT J AU Saadatpour, A Guo, GJ Orkin, SH Yuan, GC AF Saadatpour, Assieh Guo, Guoji Orkin, Stuart H. Yuan, Guo-Cheng TI Characterizing heterogeneity in leukemic cells using single-cell gene expression analysis SO GENOME BIOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; CIRCULATING TUMOR-CELLS; MESSENGER-RNA-SEQ; STEM-CELLS; HEMATOPOIETIC STEM; NETWORK ANALYSIS; MASS CYTOMETRY; PROGENITOR CELLS; SELF-RENEWAL; BLOOD STEM AB Background: A fundamental challenge for cancer therapy is that each tumor contains a highly heterogeneous cell population whose structure and mechanistic underpinnings remain incompletely understood. Recent advances in single-cell gene expression profiling have created new possibilities to characterize this heterogeneity and to dissect the potential intra-cancer cellular hierarchy. Results: Here, we apply single-cell analysis to systematically characterize the heterogeneity within leukemic cells using the MLL-AF9 driven mouse model of acute myeloid leukemia. We start with fluorescence-activated cell sorting analysis with seven surface markers, and extend by using a multiplexing quantitative polymerase chain reaction approach to assay the transcriptional profile of a panel of 175 carefully selected genes in leukemic cells at the single-cell level. By employing a set of computational tools we find striking heterogeneity within leukemic cells. Mapping to the normal hematopoietic cellular hierarchy identifies two distinct subtypes of leukemic cells; one similar to granulocyte/monocyte progenitors and the other to macrophage and dendritic cells. Further functional experiments suggest that these subtypes differ in proliferation rates and clonal phenotypes. Finally, co-expression network analysis reveals similarities as well as organizational differences between leukemia and normal granulocyte/monocyte progenitor networks. Conclusions: Overall, our single-cell analysis pinpoints previously uncharacterized heterogeneity within leukemic cells and provides new insights into the molecular signatures of acute myeloid leukemia. C1 [Saadatpour, Assieh; Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Saadatpour, Assieh; Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Guo, Guoji; Orkin, Stuart H.] Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Guo, Guoji; Orkin, Stuart H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Guo, Guoji; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Guo, Guoji; Orkin, Stuart H.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Guo, Guoji] Zhejiang Univ, Sch Med, Ctr Stem Cell & Regenerat Med, Hangzhou 310058, Zhejiang, Peoples R China. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu; gcyuan@jimmy.harvard.edu FU Harvard Stem Cell Institute; NIH [R01HG005085, P30DK049216] FX This work was in part supported by a pilot grant from Harvard Stem Cell Institute (to SHO and G-CY), and the NIH grants R01HG005085(to G-CY) and P30DK049216(to SHO). We thank Drs Kimberly Glass and Michael Love for useful discussions. NR 59 TC 17 Z9 18 U1 0 U2 10 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 525 DI 10.1186/s13059-014-0525-9 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AW9XX UT WOS:000346609500007 PM 25517911 ER PT J AU Trinh, A Rye, IH Almendro, V Helland, A Russnes, HG Markowetz, F AF Trinh, Anne Rye, Inga H. Almendro, Vanessa Helland, Aslaug Russnes, Hege G. Markowetz, Florian TI GoIFISH: a system for the quantification of single cell heterogeneity from IFISH images SO GENOME BIOLOGY LA English DT Article ID TUMOR EVOLUTION; ACTIVE CONTOURS; BREAST-CANCER; DIVERSITY; TISSUE AB Molecular analysis has revealed extensive intra-tumor heterogeneity in human cancer samples, but cannot identify cell-to-cell variations within the tissue microenvironment. In contrast, in situ analysis can identify genetic aberrations in phenotypically defined cell subpopulations while preserving tissue-context specificity. GoIFISH is a widely applicable, user-friendly system tailored for the objective and semi-automated visualization, detection and quantification of genomic alterations and protein expression obtained from fluorescence in situ analysis. In a sample set of HER2-positive breast cancers GoIFISH is highly robust in visual analysis and its accuracy compares favorably to other leading image analysismethods. GoIFISH is freely available at www.sourceforge.net/projects/goifish/. C1 [Trinh, Anne; Markowetz, Florian] Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England. [Rye, Inga H.; Helland, Aslaug; Russnes, Hege G.] Inst Canc Res, Dept Genet, N-0424 Oslo, Norway. [Rye, Inga H.; Helland, Aslaug; Russnes, Hege G.] Univ Oslo, KG Jebsen Ctr Breast Canc Res, N-0424 Oslo, Norway. [Almendro, Vanessa] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Almendro, Vanessa] Harvard Univ, Sch Med, Boston, MA USA. [Helland, Aslaug] Oslo Univ Hosp, Dept Canc Treatment, N-0424 Oslo, Norway. [Russnes, Hege G.] Oslo Univ Hosp, Dept Pathol, N-0424 Oslo, Norway. RP Russnes, HG (reprint author), Inst Canc Res, Dept Genet, Postboks 4950, N-0424 Oslo, Norway. EM Hege.Russnes@rr-research.no RI Helland, Aslaug/H-3910-2015; Russnes, Hege/N-6170-2015; OI Helland, Aslaug/0000-0002-5520-0275; Russnes, Hege/0000-0001-8724-1891; Markowetz, Florian/0000-0002-2784-5308 FU University of Cambridge; Helse Sor-Ost; Norwegian Cancer Association; K. G. Jebsen Foundation; Breast Cancer Research Foundation; National Cancer Institute [U54CA143798]; Radiumhospitalets legater; Cancer Research UK; Hutchison Whampoa Limited FX We would like to thank Prof. Kornelia Polyak and Prof. Anne-Lise Borresen-Dale for support and insightful discussions. AT and FM would like to acknowledge the support of The University of Cambridge, Cancer Research UK and Hutchison Whampoa Limited. IHR and HGR would like to acknowledge support from Helse Sor-Ost, The Norwegian Cancer Association, the K. G. Jebsen Foundation and Radiumhospitalets legater. VA would like to thank the Breast Cancer Research Foundation and the National Cancer Institute (grant U54CA143798). NR 27 TC 4 Z9 4 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2014 VL 15 IS 8 AR 442 DI 10.1186/s13059-014-0442-y PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AW9UU UT WOS:000346604100022 PM 25168174 ER PT J AU Zheng, XQ Zhao, Q Wu, HJ Li, W Wang, HY Meyer, CA Qin, QA Xu, H Zang, CZ Jiang, P Li, FQ Hou, YQ He, JX Wang, J Wang, J Zhang, P Zhang, Y Liu, XS AF Zheng, Xiaoqi Zhao, Qian Wu, Hua-Jun Li, Wei Wang, Haiyun Meyer, Clifford A. Qin, Qian Alvin Xu, Han Zang, Chongzhi Jiang, Peng Li, Fuqiang Hou, Yong He, Jianxing Wang, Jun Wang, Jun Zhang, Peng Zhang, Yong Liu, Xiaole Shirley TI MethylPurify: tumor purity deconvolution and differential methylation detection from single tumor DNA methylomes SO GENOME BIOLOGY LA English DT Article ID COPY-NUMBER ALTERATION; EPIGENETIC INACTIVATION; CLONAL EVOLUTION; HUMAN CANCERS; HYPOMETHYLATION; GENE; IDENTIFICATION; RESOLUTION; LANDSCAPE; GENOME AB We propose a statistical algorithm MethylPurify that uses regions with bisulfite reads showing discordant methylation levels to infer tumor purity from tumor samples alone. MethylPurify can identify differentially methylated regions (DMRs) from individual tumor methylome samples, without genomic variation information or prior knowledge from other datasets. In simulations with mixed bisulfite reads from cancer and normal cell lines, MethylPurify correctly inferred tumor purity and identified over 96% of the DMRs. From patient data, MethylPurify gave satisfactory DMR calls from tumor methylome samples alone, and revealed potential missed DMRs by tumor to normal comparison due to tumor heterogeneity. C1 [Zheng, Xiaoqi; Wang, Jun] Shanghai Normal Univ, Dept Math, Shanghai, Peoples R China. [Zheng, Xiaoqi; Wu, Hua-Jun; Li, Wei; Meyer, Clifford A.; Xu, Han; Zang, Chongzhi; Jiang, Peng; Liu, Xiaole Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Zheng, Xiaoqi; Wu, Hua-Jun; Li, Wei; Meyer, Clifford A.; Xu, Han; Zang, Chongzhi; Jiang, Peng; Liu, Xiaole Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Zhao, Qian; Wang, Haiyun; Qin, Qian Alvin; Zhang, Yong] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. [Zhao, Qian] Tongji Univ, Adv Inst, Shanghai 200092, Peoples R China. [Li, Wei; Meyer, Clifford A.; Qin, Qian Alvin; Xu, Han; Zang, Chongzhi; Jiang, Peng; Liu, Xiaole Shirley] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02115 USA. [Li, Fuqiang; Hou, Yong; Wang, Jun] BGI Shenzhen, Shenzhen, Peoples R China. [He, Jianxing] Guangzhou Med Univ, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China. [Wang, Jun] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark. [Wang, Jun] King Abdulaziz Univ, Princess Al Jawhara Ctr Excellence Res Hereditary, Jeddah 21589, Saudi Arabia. [Wang, Jun] Macau Univ Sci & Technol, Macau 999078, Peoples R China. [Wang, Jun] Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China. [Zhang, Peng] Tongji Univ, Shanghai Pulm Hosp, Sch Med, Dept Thorac Surg, Shanghai 200092, Peoples R China. RP Zhang, P (reprint author), Tongji Univ, Shanghai Pulm Hosp, Sch Med, Dept Thorac Surg, Shanghai 200092, Peoples R China. EM zhangpeng1121@aliyun.com; yzhang@tongji.edu.cn; xsliu@jimmy.harvard.edu RI Wang, Jun/C-8434-2016; Zang, Chongzhi/D-1445-2011; Zhang, Yong/B-4838-2011; Wang, Jun/B-9503-2016; OI Wang, Jun/0000-0002-8540-8931; Zhang, Yong/0000-0001-6316-2734; Wang, Jun/0000-0002-2113-5874; hou, yong/0000-0002-0420-0726 FU National Natural Science Foundations of China [31100953, 31329003, 31200949, 31322031, 31371288]; Shanghai Municipal Education Commission [12YZ088]; National Institutes of Health of US [GM099409] FX The authors thank Bing Ren and Gary Hon for sharing their WGBS data and the list of allele-specific methylated regions and Alex Meissner for sharing their RRBS raw data to test MethylPurify. We also thank Dr. Franziska Michor for the helpful advices on modeling and sequence analysis aspects of the project. This work was funded by the National Natural Science Foundations of China (No. 31100953 to XZ; 31329003 to XSL; 31200949 to QZ; 31322031 and 31371288 to YZ.), Innovation Program of Shanghai Municipal Education Commission (No. 12YZ088 to XZ), and National Institutes of Health of US (GM099409 to XSL). NR 55 TC 19 Z9 20 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2014 VL 15 IS 8 AR 419 DI 10.1186/s13059-014-0419-x PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AW9UU UT WOS:000346604100005 PM 25103624 ER PT J AU Li, XH Wang, EL Zhou, HM Yoshimoto, K Qian, ZR AF Li, Xu-Hui Wang, Elaine Lu Zhou, Hai-Meng Yoshimoto, Katsuhiko Qian, Zhi Rong TI MicroRNAs in Human Pituitary Adenomas SO INTERNATIONAL JOURNAL OF ENDOCRINOLOGY LA English DT Review ID CHRONIC LYMPHOCYTIC-LEUKEMIA; SQUAMOUS-CELL CARCINOMA; TUMOR-SUPPRESSOR GENE; HUMAN BREAST-CANCER; MOBILITY GROUP A2; DOWN-REGULATION; COLON-CANCER; COLORECTAL-CANCER; SIGNALING PATHWAY; GASTRIC-CANCER AB MicroRNAs (miRNAs) are a class of recently identified noncoding RNAs that regulate gene expression at posttranscriptional level. Due to the large number of genes regulated by miRNAs, miRNAs play important roles in many cellular processes. Emerging evidence indicates that miRNAs are dysregulated in pituitary adenomas, a class of intracranial neoplasms which account for 10-15% of diagnosed brain tumors. Deregulated miRNAs and their targets contribute to pituitary adenomas progression and are associated with cell cycle control, apoptosis, invasion, and pharmacological treatment of pituitary adenomas. To provide an overview of miRNAs dysregulation and functions of these miRNAs in pituitary adenoma progression, we summarize the deregulated miRNAs and their targets to shed more light on their potential as therapeutic targets and novel biomarkers. C1 [Li, Xu-Hui] Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China. [Li, Xu-Hui; Zhou, Hai-Meng] Tsinghua Univ, Yangtze Delta Reg Inst, Zhejiang Prov Key Lab Appl Enzymol, Jiaxing 314006, Zhejiang, Peoples R China. [Wang, Elaine Lu] Kanazawa Med Univ, Dept Legal Med, Uchinada, Ishikawa 9200293, Japan. [Wang, Elaine Lu; Qian, Zhi Rong] Univ Tokushima, Grad Sch, Inst Hlth Biosci, Dept Pathol, Tokushima 7708503, Japan. [Yoshimoto, Katsuhiko] Univ Tokushima, Grad Sch, Inst Hlth Biosci, Dept Med Pharmacol, Tokushima 7708504, Japan. [Qian, Zhi Rong] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02215 USA. [Qian, Zhi Rong] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Li, XH (reprint author), Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China. EM lixuhui_2013@tsinghua.org.cn; zhirong_qian@dfci.harvard.edu FU Natural Science Foundation of Zhejiang Province [LY14C060002]; Science and Technology Bureau of Jiaxing [2014AY21022]; Open Fund of Zhejiang Provincial Top Key Discipline of Biology; Science and Technology of Xiaoshan District [2012121]; China Natural Science Foundation [31170732, 31270854] FX This work was supported by the Natural Science Foundation of Zhejiang Province (no. LY14C060002); the fund from the Science and Technology Bureau of Jiaxing (no. 2014AY21022); the Open Fund of Zhejiang Provincial Top Key Discipline of Biology; the fund from Science and Technology of Xiaoshan District (no. 2012121); and the China Natural Science Foundation (no. 31170732 and no. 31270854). NR 101 TC 0 Z9 0 U1 1 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-8337 EI 1687-8345 J9 INT J ENDOCRINOL JI Int. J. Endocrinol. PY 2014 AR 435171 DI 10.1155/2014/435171 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX1NG UT WOS:000346713000001 ER PT S AU Sabuncu, MR AF Sabuncu, Mert R. BE Golland, P Hata, N Barillot, C Hornegger, J Howe, R TI A Universal and Efficient Method to Compute Maps from Image-Based Prediction Models SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2014, PT III SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 17th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) CY SEP 14-18, 2014 CL Massachusetts Inst Technol, Boston, MA SP Harvard Med Sch HO Massachusetts Inst Technol DE Machine learning; image-based prediction ID ALZHEIMERS-DISEASE; CLASSIFICATION; MRI; AD AB Discriminative supervised learning algorithms, such as Support Vector Machines, are becoming increasingly popular in biomedical image computing. One of their main uses is to construct image-based prediction models, e.g., for computer aided diagnosis or "mind reading." A major challenge in these applications is the biological interpretation of the machine learning models, which can be arbitrarily complex functions of the input features (e.g., as induced by kernel-based methods). Recent work has proposed several strategies for deriving maps that highlight regions relevant for accurate prediction. Yet most of these methods either rely on strong assumptions about the prediction model (e.g., linearity, sparsity) and/or data (e.g., Gaussianity), or fail to exploit the covariance structure in the data. In this work, we propose a computationally efficient and universal framework for quantifying associations captured by black box machine learning models. Furthermore, our theoretical perspective reveals that examining associations with predictions, in the absence of ground truth labels, can be very informative. We apply the proposed method to machine learning models trained to predict cognitive impairment from structural neuroimaging data. We demonstrate that our approach yields biologically meaningful maps of association. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Sabuncu, MR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. NR 20 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-10443-0; 978-3-319-10442-3 J9 LECT NOTES COMPUT SC PY 2014 VL 8675 BP 353 EP 360 PG 8 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging GA BB8BN UT WOS:000346250200045 ER PT J AU Bardeesy, N AF Bardeesy, Nabeel TI Insights Into Pancreatic Cancer Metabolism SO ONCOLOGIST LA English DT Meeting Abstract C1 [Bardeesy, Nabeel] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 PY 2014 VL 19 SU 1 MA 1 BP S1 EP S1 PG 1 WC Oncology SC Oncology GA AX0SF UT WOS:000346661400002 ER PT J AU Bardia, A AF Bardia, Aditya TI Molecular Interrogation of Circulating Tumor Cells for Drug Development in Breast Cancer SO ONCOLOGIST LA English DT Meeting Abstract C1 [Bardia, Aditya] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 PY 2014 VL 19 SU 1 MA 9 BP S4 EP S4 PG 1 WC Oncology SC Oncology GA AX0SF UT WOS:000346661400010 ER PT J AU Cote, GM AF Cote, Gregory M. TI Targeting EZH2 in SWI/SNF Altered Sarcomas SO ONCOLOGIST LA English DT Meeting Abstract C1 [Cote, Gregory M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 PY 2014 VL 19 SU 1 MA 12 BP S5 EP S5 PG 1 WC Oncology SC Oncology GA AX0SF UT WOS:000346661400013 ER PT J AU Graubert, TA AF Graubert, Timothy A. TI Molecular Profile of Acute Myeloid Leukemia SO ONCOLOGIST LA English DT Meeting Abstract C1 [Graubert, Timothy A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 PY 2014 VL 19 SU 1 MA 6 BP S3 EP S3 PG 1 WC Oncology SC Oncology GA AX0SF UT WOS:000346661400007 ER PT J AU Hata, AN AF Hata, Aaron N. TI Evolution of Acquired Resistance to Targeted Therapies in Lung Cancer SO ONCOLOGIST LA English DT Meeting Abstract C1 [Hata, Aaron N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 PY 2014 VL 19 SU 1 MA 10 BP S4 EP S4 PG 1 WC Oncology SC Oncology GA AX0SF UT WOS:000346661400011 ER PT J AU Hodi, FS AF Hodi, F. Stephen TI Immune Checkpoint Therapy SO ONCOLOGIST LA English DT Meeting Abstract C1 [Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 PY 2014 VL 19 SU 1 MA 5 BP S3 EP S3 PG 1 WC Oncology SC Oncology GA AX0SF UT WOS:000346661400006 ER PT J AU Mostoslavsky, R AF Mostoslavsky, Raul TI The Histone Deacetylase SIRT6: Linking Epigenetics to Cancer Metabolism SO ONCOLOGIST LA English DT Meeting Abstract C1 [Mostoslavsky, Raul] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 PY 2014 VL 19 SU 1 MA 2 BP S1 EP S1 PG 1 WC Oncology SC Oncology GA AX0SF UT WOS:000346661400003 ER PT J AU Saha, S AF Saha, Supriya TI Models for IDH Mutant Cholangiocarcinoma SO ONCOLOGIST LA English DT Meeting Abstract C1 [Saha, Supriya] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 PY 2014 VL 19 SU 1 MA 11 BP S5 EP S5 PG 1 WC Oncology SC Oncology GA AX0SF UT WOS:000346661400012 ER PT J AU Williams, AR Williams, DD Williams, PD AF Williams, Arthur R. Williams, David D. Williams, Phoebe D. BE Ortuno, F Rojas, I TI The Development and Application of an Oncology Therapy-Related Symptom Checklist for Adults (TRSC) and Children (TRSC-C) SO PROCEEDINGS IWBBIO 2014: INTERNATIONAL WORK-CONFERENCE ON BIOINFORMATICS AND BIOMEDICAL ENGINEERING, VOLS 1 AND 2 LA English DT Proceedings Paper CT 2nd International Work-Conference on Bioinformatics and Biomedical Engineering (IWBBIO) CY APR 07-09, 2014 CL Granada, SPAIN SP Univ Granada, IEEE Computat Intelligence Soc, Spanish Chapter, BioMed Central, e Health Business Dev BULL Espana S A ID CANCER AB Background: Studies found that treatment symptoms of concern to oncology/hematology patients were greatly under-documented in medical records: on average 11.0 symptoms by patient report versus 1.5 in medical records. Studies now indicate that a solution to this problem and improved patient outcomes is use of a quick, clinic-friendly, easy to use symptom checklist just before medical consultations with patients. Purposes: Describe the oncology Therapy-Related Symptom Checklists for Adults (TRSC) and Children (TRSC-C). The TRSC has 25 items/symptoms and the TRSC-C 30 items/symptoms, and these items capture up to 90% of symptoms mentioned by patients. Measurement properties and applications with outpatients are presented. Informatics applications are indicated. Methods: The TRSC was developed for adults (N=282) then modified for children (N=385). Statistical analyses have been done using correlational, epidemiologic, and qualitative methods. Extensive validation of measurement properties has been completed. Integration of the checklists into electronic/computer systems is proceeding. Findings: Completed research has found high levels of patient/clinician satisfaction, no increase in clinic costs, and strong correlations of TRSC/TRSC-C scores with the number of patient symptoms documented/managed, functional status, and quality of life. A recently published sequential cohort trial with adult outpatients at a Mayo Clinic community cancer center found TRSC use produced a 7.2% higher patient quality of life, 116% more symptoms documented/managed, and higher functional status. Other TRSC/TRSC-C study findings are presented in papers in this special session. Conclusion: A symptom checklist (TRSC/TRSC-C) can facilitate monitoring, management of symptoms, and informatics applications helpful to patients and clinicians. Implications: Gathering information about symptom occurrence and severity can optimize cancer care. TRSC studies suggest that electronic applications are a next step. C1 [Williams, Arthur R.] US Dept Vet Affairs, CINDRR, Washington, DC 20420 USA. RP Williams, AR (reprint author), US Dept Vet Affairs, CINDRR, Washington, DC 20420 USA. EM arthur.williams1@va.gov; ddwilliams@cmh.edu; pwilliam@kumc.edu NR 10 TC 1 Z9 1 U1 0 U2 1 PU COPICENTRO GRANADA S L PI GRANADA PA AV ANDALUCIA, 38, GRANADA, GRANADA 18014, SPAIN BN 978-84-15814-84-9 PY 2014 BP 298 EP 307 PG 10 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA BB8CY UT WOS:000346381500034 ER PT J AU Alemi, F Hesham, H Williams, AR Williams, PD Donley, B Kheirbek, RE AF Alemi, F. Hesham, H. Williams, A. R. Williams, P. D. Donley, B. Kheirbek, R. E. BE Ortuno, F Rojas, I TI Computers that Show Recognition of Patients' Symptoms SO PROCEEDINGS IWBBIO 2014: INTERNATIONAL WORK-CONFERENCE ON BIOINFORMATICS AND BIOMEDICAL ENGINEERING, VOLS 1 AND 2 LA English DT Proceedings Paper CT 2nd International Work-Conference on Bioinformatics and Biomedical Engineering (IWBBIO) CY APR 07-09, 2014 CL Granada, SPAIN SP Univ Granada, IEEE Computat Intelligence Soc, Spanish Chapter, BioMed Central, e Health Business Dev BULL Espana S A DE Symptoms' recognition; Feedback loop; Symptom management; Man machine interaction; Therapy-Related Symptom Checklist; Cancer ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE AB The goal of automated symptom management has often been narrowly defined as collection and reporting of data. Yet, an automated system can do more. These systems can mimic human reassurance for patients that their symptoms have been recognized. Patient engagement has long been recognized as central in symptom management. An electronic system was built to collect the Treatment Related Symptom Checklist (TRSC) and to reassure patients. In this paper we discuss the design of the system and procedures taken to show recognition of patients' symptoms. The literature on clinician-patient interactions was reviewed selectively. Methods used by clinicians to promote patient engagement during medical history were identified. Similar methods were incorporated into the symptom management system in order to facilitate understanding by the patient. These included (a) conversational data collection as opposed to survey style or standardized questionnaires, (b) short response phrases indicating understanding of the reported symptom, (c) use of open ended questions to reduce asking long lists of symptoms, (d) leading questions that ask for confirmation of expected symptoms, (e) review of symptoms at designated stages, and (d) alerting patients when computer has informed the clinician about patient-reported symptoms. We are in the process of pilot testing the system among oncology patients in one hospital. Examination of existing informatics knowledge eases integration of well established paper-based tools into automated systems. C1 [Alemi, F.; Hesham, H.] Dist Columbia Vet Adm Med Ctr, Washington, DC 20544 USA. [Williams, A. R.] Univ S Florida, US Dept Vet Affairs, Tampa, FL USA. [Williams, P. D.] Univ Kansas, Med Ctr, Sch Nursing, Kansas City, KS USA. [Donley, B.] Quaso LLC, Montross, VA USA. [Kheirbek, R. E.] Med Ctr, Washington, DC USA. RP Alemi, F (reprint author), Dist Columbia Vet Adm Med Ctr, Washington, DC 20544 USA. EM farrokh.alemi@va.gov; hosai.hesham@va.gov; arthur.williams1@va.gov; pwilliam@kumc.edu; blaine.donley@quaso.com; raya.kheirbek@va.gov NR 18 TC 0 Z9 0 U1 0 U2 0 PU COPICENTRO GRANADA S L PI GRANADA PA AV ANDALUCIA, 38, GRANADA, GRANADA 18014, SPAIN BN 978-84-15814-84-9 PY 2014 BP 321 EP 329 PG 9 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA BB8CY UT WOS:000346381500037 ER PT J AU Fleehart, S Fan, VS Nguyen, HQ Lee, J Kohen, R Herting, JR Matute-Bello, G Adams, SG Pagalilauan, G Borson, S AF Fleehart, Sara Fan, Vincent S. Nguyen, Huong Q. Lee, Jungeun Kohen, Ruth Herting, Jerald R. Matute-Bello, Gustavo Adams, Sandra G. Pagalilauan, Genevieve Borson, Soo TI Prevalence and correlates of suicide ideation in patients with COPD: a mixed methods study SO INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Article DE depression; qualitative; PHQ-9; suicide; pulmonary disease; chronic obstructive ID OBSTRUCTIVE PULMONARY-DISEASE; QUALITY-OF-LIFE; HOSPITAL READMISSION; DEPRESSIVE SYMPTOMS; PRIMARY-CARE; RISK-FACTORS; SHORT-FORM; ANXIETY; MORTALITY; EXACERBATIONS AB Purpose: The purpose of this study was to examine the prevalence and correlates of suicidal ideation (SI) in patients with stable moderate to very severe chronic obstructive pulmonary disease (COPD). Patients and methods: We conducted an exploratory mixed methods analysis of data from participants in a longitudinal observational study of depression in COPD. We measured depression with the Patient Health Questionnaire-9 (PHQ-9), which includes an item on SI. We compared participants with and without SI in relation to sociodemographics, symptoms, anxiety, and healthcare resource use with independent t-tests and chi-square tests. Content analysis was performed on qualitative data gathered during a structured SI safety assessment. Results: Of 202 participants, 121 (60%) had depressive symptoms (PHQ >= 6); 51 (25%) had a PHQ-9 >= 10, indicating a high likelihood of current major depression; and 22 (11%) reported SI. Compared to the 99 depressed participants without SI, those with SI were more likely to be female (59% vs 27%, P=0.004); had worse dyspnea (P=0.009), depression (P<0.001), and anxiety (P=0.003); and were also more likely to have received treatment for depression and/or anxiety (82% vs 40%, P<0.001) and more hospitalizations for COPD exacerbations (P=0.03) but had similar levels of airflow obstruction and functioning than participants without SI. Themes from the qualitative analysis among those with SI included current or prior adverse life situations, untreated or partially treated complex depression, loss of a key relationship, experience of illness and disability, and poor communication with providers. Conclusion: Our findings suggest that current SI is common in COPD, may occur disproportionately in women, can persist despite mental health treatment, and has complex relationships with both health and life events. Adequate management of SI in COPD may therefore require tailored, comprehensive treatment approaches that integrate medical and mental health objectives. C1 [Fleehart, Sara; Lee, Jungeun] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Fan, Vincent S.; Matute-Bello, Gustavo] VAPuget Sound Hlth Care Ctr, Seattle, WA USA. [Fan, Vincent S.; Kohen, Ruth; Matute-Bello, Gustavo; Pagalilauan, Genevieve; Borson, Soo] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Nguyen, Huong Q.] Kaiser Permanente So Calif, Res & Evaluat, Pasadena, CA 91101 USA. [Herting, Jerald R.] Univ Washington, Dept Sociol, Seattle, WA 98195 USA. [Adams, Sandra G.] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, San Antonio, TX 78229 USA. [Adams, Sandra G.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Borson, S (reprint author), Univ Washington, Sch Med, Box 356560,1959 NE Pacific St, Seattle, WA 98195 USA. EM soob@uw.edu FU Department of Veterans Affairs [5R01HL093146, UL1RR025014.] FX We would like to express our heartfelt gratitude to all the study participants. This work was supported in part by: 5R01HL093146 and UL1RR025014. Dr Fan has funding through the Department of Veterans Affairs. NR 33 TC 2 Z9 2 U1 2 U2 7 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2005 J9 INT J CHRONIC OBSTR JI Int. J. Chronic Obstr. Pulm. Dis. PY 2014 VL 9 BP 1321 EP 1329 DI 10.2147/COPD.S65507 PG 9 WC Respiratory System SC Respiratory System GA AW2LZ UT WOS:000346120800001 ER PT S AU Heinemann, U Staley, KJ AF Heinemann, Uwe Staley, Kevin J. BE Scharfman, HE Buckmaster, PS TI What Is the Clinical Relevance of In Vitro Epileptiform Activity? SO ISSUES IN CLINICAL EPILEPTOLOGY: A VIEW FROM THE BENCH SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT Workshop on Issues in Clinical Epileptology - A View from the Bench held in honor of Phil CY MAY 03-05, 2013 CL Watsonville, CA DE Seizure; Epilepsy; Epileptogenisis; In vitro models; Translation; Ictal; Interictal ID HIPPOCAMPAL SLICE CULTURES; TEMPORAL-LOBE EPILEPSY; BRAIN-BARRIER DYSFUNCTION; STANDARD ANTIEPILEPTIC DRUGS; ENTORHINAL CORTEX SLICES; RAT HIPPOCAMPAL; SPREADING DEPOLARIZATION; LOW MAGNESIUM; EXTRACELLULAR POTASSIUM; SYNAPTIC-TRANSMISSION AB In vitro preparations provide an exceptionally rapid, flexible, and accessible approach to long-standing problems in epilepsy research including icto-genesis, epileptogenesis, and drug resistance. Acute slices suffer from a reduction in network connectivity that has traditionally been compensated through the application of acute convulsants. The utility and limitations of this approach have become clear over time and are discussed here. Other approaches such as organotypic slice preparations demonstrate the full spectrum of spontaneous epileptic activity and more closely mimic human responses to anticonvulsants, including the development of drug resistance. Newly developed transgenic and vector expression systems for fluorophores, optogenetics, and orphan receptors are being coupled with advances in imaging and image analysis. These developments have created the capacity to rapidly explore many new avenues of epilepsy research such as vascular, astrocytic and mitochondrial contributions to epileptogenesis. Rigorous study design as well as close collaboration with in vivo laboratories and clinical investigators will accelerate the translation of the exciting discoveries that will be revealed by these new techniques. C1 [Heinemann, Uwe] Charite, Neurosci Res Ctr, D-14195 Berlin, Germany. [Staley, Kevin J.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. RP Staley, KJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, 114 16th St, Charlestown, MA 02129 USA. EM uwe.heinemann@charite.de; kstaley@partners.org FU DFG EXC Neurocure FX UH is funded by DFG EXC Neurocure NR 98 TC 7 Z9 8 U1 2 U2 4 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0065-2598 BN 978-94-017-8914-1; 978-94-017-8913-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2014 VL 813 BP 25 EP 41 DI 10.1007/978-94-017-8914-1_2 PG 17 WC Medicine, Research & Experimental; Clinical Neurology; Neurosciences SC Research & Experimental Medicine; Neurosciences & Neurology GA BB7UO UT WOS:000346021700004 PM 25012364 ER PT S AU Houser, CR AF Houser, Carolyn R. BE Scharfman, HE Buckmaster, PS TI Do Structural Changes in GABA Neurons Give Rise to the Epileptic State? SO ISSUES IN CLINICAL EPILEPTOLOGY: A VIEW FROM THE BENCH SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT Workshop on Issues in Clinical Epileptology - A View from the Bench held in honor of Phil CY MAY 03-05, 2013 CL Watsonville, CA DE Inhibition; Plasticity; Seizures; Sprouting; Somatostatin; Parvalbumin ID TEMPORAL-LOBE EPILEPSY; SPONTANEOUS RECURRENT SEIZURES; PILOCARPINE-INDUCED SEIZURES; HILAR SOMATOSTATIN INTERNEURONS; DECARBOXYLASE MESSENGER-RNA; GAMMA-AMINOBUTYRIC-ACID; BASKET CELL HYPOTHESIS; DENTATE GRANULE CELLS; GLUTAMATE-DECARBOXYLASE; NEUROPEPTIDE-Y AB Identifying the role of GABA neurons in the development of an epileptic state has been particularly difficult in acquired epilepsy, in part because of the multiple changes that occur in such conditions. Although once questioned, there is now considerable evidence for loss of GABA neurons in multiple brain regions in models of acquired epilepsy. This loss can affect several cell types, including both somatostatin-and parvalbumin-expressing interneurons, and the cell type that is most severely affected can vary among brain regions and models. Because of the diversity of GABA neurons in the hippocampus and cerebral cortex, resulting functional deficits are unlikely to be compensated fully by remaining GABA neurons of other subtypes. The fundamental importance of GABA neuron loss in epilepsy is supported by findings in genetic mouse models in which GABA neurons appear to be decreased relatively selectively, and increased seizure susceptibility and spontaneous seizures develop. Alterations in remaining GABA neurons also occur in acquired epilepsy. These include alterations in inputs or receptors that could impair function, as well as morphological reorganization of GABAergic axons and their synaptic connections. Such axonal sprouting could be compensatory if normal circuits are reestablished, but the creation of aberrant circuitry could contribute to an epileptic condition. The functional effects of GABA neuron alterations thus may include not only reductions in GABAergic inhibition but also excessive neuronal synchrony and, potentially, depolarizing GABAergic influences. The combination of GABA neuron loss and alterations in remaining GABA neurons provides likely, though still unproven, substrates for the epileptic state. C1 [Houser, Carolyn R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. [Houser, Carolyn R.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. [Houser, Carolyn R.] Vet Adm Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. RP Houser, CR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM houser@mednet.ucla.edu FU National Institutes of Health [NS075245]; Veterans Affairs Medical Research Funds FX This work was supported by National Institutes of Health Grant NS075245 and Veterans Affairs Medical Research Funds. I gratefully acknowledge the members of my laboratory, past and present, for their superb work and strong dedication to our studies of GABA neurons and epilepsy. NR 54 TC 15 Z9 15 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0065-2598 BN 978-94-017-8914-1; 978-94-017-8913-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2014 VL 813 BP 151 EP 160 DI 10.1007/978-94-017-8914-1_12 PG 10 WC Medicine, Research & Experimental; Clinical Neurology; Neurosciences SC Research & Experimental Medicine; Neurosciences & Neurology GA BB7UO UT WOS:000346021700014 PM 25012374 ER PT J AU Sher, L AF Sher, Leo TI MEN'S MENTAL HEALTH AND SUICIDE SO PSYCHIATRIA DANUBINA LA English DT Letter C1 [Sher, Leo] James J Peters Vet Adm Med Ctr, New York, NY USA. [Sher, Leo] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM Leo.Sher@mssm.edu NR 4 TC 1 Z9 1 U1 0 U2 3 PU MEDICINSKA NAKLADA PI ZAGREB PA VLASKA 69, HR-10000 ZAGREB, CROATIA SN 0353-5053 J9 PSYCHIAT DANUB JI Psychiatr. Danub. PY 2014 VL 26 IS 3 BP 298 EP 298 PG 1 WC Psychiatry SC Psychiatry GA AW2WL UT WOS:000346147300018 PM 25191782 ER PT J AU Nakamura, Y Tanaka, T Ohnishi, T Hashimoto, N Haneishi, H Taylor, J Snuderl, M Yagi, Y AF Nakamura, Yuka Tanaka, Takuya Ohnishi, Takashi Hashimoto, Noriaki Haneishi, Hideaki Taylor, Jennie Snuderl, Matija Yagi, Yukako TI Registration between Pathological Image and MR Image for Comparing Different Modality Images of Brain Tumor SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article C1 [Nakamura, Yuka] Chiba Univ, Grad Sch Engn, Chiba 2638522, Japan. [Tanaka, Takuya] Chiba Univ, Dept Med Syst Engn, Chiba 2638522, Japan. [Ohnishi, Takashi; Hashimoto, Noriaki; Haneishi, Hideaki] Chiba Univ, Ctr Frontier Med Engn, Chiba 2638522, Japan. [Taylor, Jennie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Snuderl, Matija] NYU, Langone Med Ctr, New York, NY 10016 USA. [Yagi, Yukako] Massachusetts Gen Hosp, Pathol Imaging & Commun Technol PICT Ctr, Boston, MA 02114 USA. [Yagi, Yukako] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Nakamura, Y (reprint author), Chiba Univ, Grad Sch Engn, Chiba 2638522, Japan. EM ynakamura@chiba-u.jp OI Snuderl, Matija/0000-0003-0752-0917 FU JSPS [25560189] FX This work was partly supported by JSPS Grants-in-Aid for Challenging Exploratory Research Grant no. 25560189. The authors acknowledge Dr. Tracy Batechlor, Dr. Elizabeth Gerstner, and Dr. Christine Lu-Emerson for their contribution to the project. NR 0 TC 0 Z9 0 U1 0 U2 1 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 UNSP 430762 DI 10.1155/2014/430762 PG 3 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA AW0QE UT WOS:000345997300001 ER PT J AU Menon, S Smith, MW Sittig, DF Petersen, NJ Hysong, SJ Espadas, D Modi, V Singh, H AF Menon, Shailaja Smith, Michael W. Sittig, Dean F. Petersen, Nancy J. Hysong, Sylvia J. Espadas, Donna Modi, Varsha Singh, Hardeep TI How context affects electronic health record-based test result follow-up: a mixed-methods evaluation SO BMJ OPEN LA English DT Article ID PATIENT SAFETY; PRIMARY-CARE; MEDICAL-RECORD; INFORMATION; MANAGEMENT; SYSTEM; IMPLEMENTATION; INTERVENTIONS; NOTIFICATION; FREQUENCY AB Objectives: Electronic health record (EHR)-based alerts can facilitate transmission of test results to healthcare providers, helping ensure timely and appropriate follow-up. However, failure to follow-up on abnormal test results (missed test results) persists in EHR-enabled healthcare settings. We aimed to identify contextual factors associated with facility-level variation in missed test results within the Veterans Affairs (VA) health system. Design, setting and participants: Based on a previous survey, we categorised VA facilities according to primary care providers' (PCPs') perceptions of low (n=20) versus high (n=20) risk of missed test results. We interviewed facility representatives to collect data on several contextual factors derived from a sociotechnical conceptual model of safe and effective EHR use. We compared these factors between facilities categorised as low and high perceived risk, adjusting for structural characteristics. Results: Facilities with low perceived risk were significantly more likely to use specific strategies to prevent alerts from being lost to follow-up (p=0.0114). Qualitative analysis identified three high-risk scenarios for missed test results: alerts on tests ordered by trainees, alerts 'handed off' to another covering clinician (surrogate clinician), and alerts on patients not assigned in the EHR to a PCP. Test result management policies and procedures to address these high-risk situations varied considerably across facilities. Conclusions: Our study identified several scenarios that pose a higher risk for missed test results in EHR-based healthcare systems. In addition to implementing provider-level strategies to prevent missed test results, healthcare organisations should consider implementing monitoring systems to track missed test results. C1 [Menon, Shailaja; Smith, Michael W.; Petersen, Nancy J.; Hysong, Sylvia J.; Espadas, Donna; Modi, Varsha; Singh, Hardeep] Baylor Coll Med, Dept Med, Ctr Innovat Qual Effectiveness & Safety, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Menon, Shailaja; Smith, Michael W.; Petersen, Nancy J.; Hysong, Sylvia J.; Espadas, Donna; Modi, Varsha; Singh, Hardeep] Sect Hlth Serv Res, Houston, TX USA. [Sittig, Dean F.] Univ Texas Houston, Sch Biomed Informat, Houston, TX USA. [Sittig, Dean F.] UT Mem Hermann Ctr Healthcare Qual & Safety, Houston, TX USA. RP Singh, H (reprint author), Baylor Coll Med, Dept Med, Ctr Innovat Qual Effectiveness & Safety, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. EM hardeeps@bcm.edu RI Hysong, Sylvia/B-8420-2008 OI Hysong, Sylvia/0000-0002-9063-5207 FU VA National Center of Patient Safety; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development; Center for Innovations in Quality, Effectiveness and Safety [CIN 13-413]; AHRQ; VA HSR&D Center for Innovations in Quality, Effectiveness and Safety [CIN 13-413] FX This work was supported by the VA National Center of Patient Safety and partially supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and the Center for Innovations in Quality, Effectiveness and Safety (#CIN 13-413). SM is supported by AHRQ training fellowship in Patient Safety and Quality and partially supported with resources at the VA HSR&D Center for Innovations in Quality, Effectiveness and Safety (#CIN 13-413), at the Michael E. DeBakey VA Medical Center, Houston, TX. NR 42 TC 7 Z9 7 U1 1 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2014 VL 4 IS 11 AR e005985 DI 10.1136/bmjopen-2014-005985 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AU7EA UT WOS:000345762300036 PM 25387758 ER PT J AU Ross, JS Russo, SB Chavis, GC Cowart, LA AF Ross, Jessica S. Russo, Sarah B. Chavis, Georgia C. Cowart, Lauren A. TI Sphingolipid regulators of cellular dysfunction in Type 2 diabetes mellitus: a systems overview SO CLINICAL LIPIDOLOGY LA English DT Review DE free fatty acids; lipotoxicity; obesity; sphingolipid; Type 2 diabetes mellitus ID NECROSIS-FACTOR-ALPHA; FREE FATTY-ACIDS; INDUCED INSULIN-RESISTANCE; ACTIVATED RECEPTOR-ALPHA; LOW-DENSITY-LIPOPROTEIN; PANCREATIC BETA-CELLS; ISCHEMIC/REPERFUSED RAT-HEART; ENDOPLASMIC-RETICULUM STRESS; INDUCED CARDIAC-HYPERTROPHY; CORONARY-ARTERY-DISEASE AB Climbing obesity rates have contributed to worldwide increases in obesity-associated diseases, including the metabolic syndrome and Type 2 diabetes mellitus (T2DM). Sphingolipids, an important class of structural and signaling lipids, have emerged as key players in the development and pathogenesis of insulin resistance and T2DM. More specifically, sphingolipids have been demonstrated to play integral roles in lipotoxicity and other aspects of pathogenesis in T2DM, although the cellular mechanisms by which this occurs and by which sphingolipid metabolism is dysregulated in T2DM remain under investigation. This review summarizes current knowledge of sphingolipid metabolism and signaling in key organs and tissues affected by T2DM, including the pancreas, adipose tissue, skeletal muscle, cardiovascular system and liver, and highlights areas that ripe for future investigation. C1 [Ross, Jessica S.; Russo, Sarah B.; Chavis, Georgia C.; Cowart, Lauren A.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Cowart, Lauren A.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Cowart, LA (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. EM cowartl@musc.edu FU NIH [1RO1HL117233, 5P30 GM103339-03]; Veteran's Affairs Merit Award [210 IBX000200-04A2, T32 HL007260-38] FX This work was supported in part by NIH Grants 1RO1HL117233 and 5P30 GM103339-03, Veteran's Affairs Merit Award 210 IBX000200-04A2, all to LA Cowart, and T32 HL007260-38, to SB Russo. 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 188 TC 0 Z9 0 U1 2 U2 7 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-4299 EI 1758-4302 J9 CLIN LIPIDOL JI Clin. Lipidol. PY 2014 VL 9 IS 5 BP 553 EP 569 DI 10.2217/CLP.14.37 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AU5LB UT WOS:000345647300009 ER PT J AU Ahmad, M Dar, NJ Bhat, ZS Hussain, A Shah, A Liu, H Graham, SH AF Ahmad, Muzamil Dar, Nawab J. Bhat, Zubair S. Hussain, Aehtesham Shah, Ayatullah Liu, Hao Graham, Steven H. TI Inflammation in Ischemic Stroke: Mechanisms, Consequences and Possible Drug Targets SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article DE Cerebral ischemia; cyclooxygenase-2; cytokines and chemokines; inflammation; microglia; middle cerebral artery occlusion; prostaglandin ID FOCAL CEREBRAL-ISCHEMIA; NITRIC-OXIDE SYNTHASE; INTERCELLULAR-ADHESION MOLECULE-1; BLOOD-BRAIN-BARRIER; MONOCYTE CHEMOATTRACTANT PROTEIN-1; TUMOR-NECROSIS-FACTOR; INTERLEUKIN-1 RECEPTOR ANTAGONIST; TRANSIENT FOREBRAIN ISCHEMIA; ANEURYSMAL SUBARACHNOID HEMORRHAGE; NEUTROPHIL INHIBITORY FACTOR AB Ischemic stroke is caused when blood flow to the brain is hampered, leading to instant deficiency of nutrients and oxygen required for normal brain functioning. Reperfusion can alleviate damage from stroke if performed immediately after the onset of ischemia however the efficacy of reperfusion is tempered by secondary injury mechanisms. This multifarious sequence of events leads to the commencement of deleterious cycles of inflammation, oxidant stress and apoptosis that finally culminate in delayed death of neuronal cells even when the brain is effectively reperfused. Wealth of data from clinical as well as experimental studies points to a prominent role of inflammation in secondary injury. In this review we will discuss, in detail, the cellular and molecular mediators of inflammation and their possible therapeutic targets in both experimental and clinical forms of stroke. C1 [Ahmad, Muzamil; Dar, Nawab J.; Bhat, Zubair S.; Hussain, Aehtesham; Shah, Ayatullah] Indian Inst Integrat Med, CSIR, Neuropharmacol Lab, Srinagar 190005, Jammu & Kashmir, India. [Ahmad, Muzamil; Dar, Nawab J.; Bhat, Zubair S.; Hussain, Aehtesham; Shah, Ayatullah] Indian Inst Integrat Med, CSIR, Acad Sci & Innovat Res, Jammu 180001, Jammu & Kashmir, India. [Liu, Hao; Graham, Steven H.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr Syst, Pittsburgh, PA 15261 USA. [Liu, Hao; Graham, Steven H.] Univ Pittsburgh, Sch Med Pittsburgh, Dept Neurol, Pittsburgh, PA USA. RP Ahmad, M (reprint author), Indian Inst Integrat Med, CSIR, Neuropharmacol Lab, Srinagar 190005, Jammu & Kashmir, India. EM mahmad@iiim.res.in OI Bhat, Zubair Shanib/0000-0003-2497-0581 FU Department of Biotechnology [MLP6009]; NIH [R01 NS37459-10]; Department of Veteran's Affairs FX Dr. Ahmad's work is partly supported by Ramalingaswamy Fellowship of Department of Biotechnology to MA and financial assistance (MLP6009) as well as logistic support from Council for Scientific and Industrial Research. Dr. Graham's work was partially supported by NIH (R01 NS37459-10) and Department of Veteran's Affairs RDD merit review program. Contents do not represent any governmental views of India or United States. NR 362 TC 20 Z9 22 U1 3 U2 10 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5273 EI 1996-3181 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PY 2014 VL 13 IS 8 BP 1378 EP 1396 PG 19 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AU6BE UT WOS:000345686300010 PM 25345517 ER PT J AU Liu, P Liu, XL Liou, AKF Xing, J Jing, Z Ji, XM Liu, XR Zhao, HP Yan, F Chen, J Cao, GD Luo, YM AF Liu, Ping Liu, Xiaolei Liou, Anthony Kian-Fong Xing, Juan Jing, Zheng Ji, Xunming Liu, Xiangrong Zhao, Haiping Yan, Feng Chen, Jun Cao, Guodong Luo, Yumin TI The Neuroprotective Mechanism of Erythropoietin-TAT Fusion Protein Against Neurodegeneration from Ischemic Brain Injury SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article DE Cerebral ischemia; erythropoietin; neurodegeneration; neuroprotection; reperfusion ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; CEREBRAL-ARTERY OCCLUSION; KIDNEY INJURY; MODULATION; ACTIVATION; PATHWAYS; NEURONS; MYOCARDIUM; PROTECTION; INFARCTION AB Aims: To compare the neuroprotection of erythropoietin (EPO) and EPO fusion protein containing transduction domain derived from HIV TAT (EPO-TAT) against ischemic brain injury, inclusive of the side effect, and explore the mechanism underlying the role of EPO-TAT in a transient focal cerebral ischemia model in rats. Methods: Transient focal ischemia was induced by middle cerebral artery occlusion (MCAO) in rats. Rats were treated, respectively, with following regimens: saline, 1000 U/kg EPO, 5000 U/kg EPO, 1000 U/kg EPO-TAT, 1000 U/kg EPOTAT + 5 mu l of 10 mM LY294002 (or/plus 5 mu l of 5 mM PD98059). Neurological deficit scores, infarct volume, and hematologic side effect were assessed at 72 hours after MCAO. Apoptotic cells were determined with TUNEL staining. The expression and localization of phosphorylated AKT (pAKT) and phosphorylated ERK (pERK) were detected with Western blot, immunohistochemistry, and immunofluorescence, respectively. Results: 1000 U/kg EPO-TAT exhibited a comparable neuroprotection to 5000 U/kg EPO, as evidenced by a comparable attenuation in neurological deficit, infarct volume, and number of apoptotic cells in the rat ischemic cortex after MCAO. The pAKT and pERK levels were significantly elevated solely in neurons of rodents receiving EPO or EPO-TAT treatments, suggesting the concurrent activation of these two pathways. Specific inhibition of either AKT or ERK pathway partially abolished EPO-TAT protection, but exhibited no influence on the activation status of its counterpart, suggesting no cross-modulation between these two protective pathways. Conclusion: Our study indicates that EPO-TAT at 1000 U/kg displays neuroprotection with no detectable side effects. The mechanism for neuroprotection may be attributable to the simultaneous activation of the AKT and ERK pathways, which preserve neuronal cell viability and attenuate behavioral deficits. C1 [Liu, Ping; Liu, Xiaolei; Ji, Xunming; Liu, Xiangrong; Zhao, Haiping; Yan, Feng; Luo, Yumin] Capital Med Univ, Xuanwu Hosp, Cerebrovasc Dis Res Inst, Beijing 100053, Peoples R China. [Liu, Xiaolei] Taiyuan Peoples Hosp, Dept Neurol, Taiyuan 030032, Shanxi, Peoples R China. [Liou, Anthony Kian-Fong; Xing, Juan; Jing, Zheng; Chen, Jun; Cao, Guodong] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Chen, Jun; Cao, Guodong] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. RP Luo, YM (reprint author), Capital Med Univ, Xuanwu Hosp, Cerebrovasc Dis Res Inst, Key Lab Neurodegenerat Dis,Minist Educ, 45 Changchun St, Beijing 100053, Peoples R China. EM caog@upmc.edu; yumin111@ccmu.edu.cn FU Chinese Natural Science Foundation [30670725, 81071058, 81471340]; National Institutes of Health [NS079345, NS053473]; Department of Veterans Affairs Merit Review [101RX000199] FX This project was supported by Chinese Natural Science Foundation grants 30670725, 81071058 and 81471340 (to Y. Luo); National Institutes of Health grant NS079345 and NS053473 (to G. Cao); and Department of Veterans Affairs Merit Review grant 101RX000199 (to G. Cao). NR 37 TC 1 Z9 3 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5273 EI 1996-3181 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PY 2014 VL 13 IS 8 BP 1465 EP 1474 PG 10 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AU6BE UT WOS:000345686300018 PM 25106625 ER PT J AU Bai, LJ Harris, RE Kong, J Lao, LX Napadow, V Zhao, BX AF Bai, Lijun Harris, Richard E. Kong, Jian Lao, Lixing Napadow, Vitaly Zhao, Baixiao TI Neurobiological Mechanisms of Acupuncture 2014 SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Editorial Material C1 [Bai, Lijun] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Dept Biomed Engn, Key Lab Biomed Informat Engn,Minist Educ, Xian 710049, Peoples R China. [Harris, Richard E.] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA. [Kong, Jian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA. [Lao, Lixing] Univ Hong Kong, Sch Chinese Med, Pokfulam, Hong Kong, Peoples R China. [Lao, Lixing] Univ Maryland, Sch Med, Ctr Integrat Med, Baltimore, MD 21201 USA. [Napadow, Vitaly] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. [Zhao, Baixiao] Beijing Univ Chinese Med, Sch Acupuncture Moxibust & Tuina, Beijing 100029, Peoples R China. RP Bai, LJ (reprint author), Xi An Jiao Tong Univ, Sch Life Sci & Technol, Dept Biomed Engn, Key Lab Biomed Informat Engn,Minist Educ, Xian 710049, Peoples R China. EM bailj4152615@gmail.com RI Bai, Lijun/C-5119-2015; OI Bai, Lijun/0000-0001-8790-5424; Lao, Lixing/0000-0003-0198-9714 NR 0 TC 0 Z9 0 U1 1 U2 8 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1741-427X EI 1741-4288 J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PY 2014 AR 765068 DI 10.1155/2014/765068 PG 2 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA AW0YM UT WOS:000346017200001 ER PT J AU Cheng, XL Pu, X Jun, P Zhu, XB Zhu, D Chen, M AF Cheng, Xianglin Pu, Xu Jun, Pen Zhu, XiaoBo Zhu, Di Chen, Ming TI Rapid and quantitative detection of C-reactive protein using quantum dots and immunochromatographic test strips SO INTERNATIONAL JOURNAL OF NANOMEDICINE LA English DT Article DE C-reactive protein; immunochromatographic test; quantum dots; fluorescence point-of-care test ID EPIDEMIOLOGIC APPLICATIONS; SENSITIVE DETECTION; IMMUNOASSAY; BIOMARKER; EVENTS; ASSAY AB Background: Rapid immunochromatographic tests can detect disease markers in 10-15 minutes, which facilitates clinical diagnosis and treatment programs. However, most immunochromatographic tests employ gold nanoparticles as reporters, and these have only moderate sensitivity and act as qualitative methods for analyzing high biomarker concentrations. Methods: In this study, we introduce quantum dots (QDs) as fluorescent probes and immunochromatographic strips to develop quantitative fluorescence point-of-care tests (QF-POCT) to analyze C-reactive protein (CRP) levels. Goat anti-rabbit IgG and rabbit IgG were used as control antibodies, and mouse monoclonal CRP antibody pairs were used for disease marker detection. One monoclonal CRP antibody was conjugated with QDs and served as a signal antibody, and the other monoclonal CRP antibody was dispensed onto the nitrocellulose membrane and served as a capturing antibody. In the presence of CRP, the fluorescence intensity of the monoclonal antibody-CRP- monoclonal antibody sandwich complex captured on the nitrocellulose membrane was determined using the fluorescence strip reader. Results: QF-POCT assays could quantitatively analyze the concentration of CRP in 15 minutes had a detection limit of 0.25 mg/L, and had a wide detection linearity range (0.5-300 mg/L). The intra-assay and interassay coefficients of variation were 8.95% and 9.86% at 0.5 mg/L, 6.47% and 8.66% at 10 mg/L, and 6.81% and 9.10% at 60 mg/L, respectively. In a comparison between clinical samples, the results of this QD-based assay of CRP levels were significantly correlated with those of an Immulite 2000 assay (R=0.993, P<0.001). Conclusion: Our results demonstrated that the QD-based immunochromatographic test is a rapid, sensitive, accurate, and quantitative method for the detection of disease biomarkers. C1 [Cheng, Xianglin; Chen, Ming] Yangtze Univ, Dept Lab Med, Affiliated Hosp 1, Jinzhou 434000, Hubei, Peoples R China. [Pu, Xu] Wuhan Univ, RenMin Hosp, Dept Lab Med, Wuhan 430072, Peoples R China. [Jun, Pen; Zhu, XiaoBo] Wuhan Univ, Coll Chem & Mol Sci, Key Lab Analyt Chem Biol & Med, Minist Educ, Wuhan 430072, Peoples R China. [Zhu, Di] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Chen, M (reprint author), Yangtze Univ, Dept Lab Med, Affiliated Hosp 1, Jinzhou 434000, Hubei, Peoples R China. EM chenmingbox@hotmail.com NR 22 TC 10 Z9 11 U1 6 U2 28 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 5619 EP 5626 DI 10.2147/IJN.S74751 PG 8 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA AU7JZ UT WOS:000345778000002 PM 25506215 ER PT J AU Dismuke, CE Hernandez-Tejada, MA Egede, LE AF Dismuke, Clara E. Hernandez-Tejada, Melba A. Egede, Leonard E. TI RELATIONSHIP OF SERIOUS PSYCHOLOGICAL DISTRESS TO QUALITY OF LIFE IN ADULTS WITH DIABETES SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE LA English DT Article DE serious psychological distress; quality of life; diabetes; SF-12 ID FACTOR SURVEILLANCE SYSTEM; MAJOR DEPRESSIVE DISORDER; US ADULTS; UNITED-STATES; RISK-FACTORS; PREVALENCE; VALIDITY; SCALES AB Objective: To examine the association between serious psychological distress (SPD) and the Physical and Mental Health components of Quality of Life (QOL) while controlling for depression in a national sample of adults with diabetes. Methods: SPD was assessed in 1,659 adults with diabetes who participated in the 2007 Medical Care Expenditure Survey (MEPS). SPD was measured by the 6-item Kessler scale. Depression was assessed with the PHQ-2 screen. Quality of life was measured with the physical (PCS) and mental (MCS) components of the SF-12. We used multiple linear regression to assess the relationship between SPD and quality of life while controlling for relevant covariates and depression screen results to assess the independent effect of SPD on QOL above and beyond the effect of depression. Results: Among US adults with diabetes, 9% had SPD and 15.4% screened positive for depression. Among those with SPD, 85.8% had depression and among those with depression, 50.5% had SPD. In the adjusted model for socio-demographic factors and comorbidities, SPD was significantly associated with lower PCS scores (-5.51 95% CI -7.55; -3.45) and MCS scores (-18.99 95% CI -20.81; -17.18). In the adjusted model that also controlled for depression, SPD was still significantly associated with lower PCS scores (-3.03 95% CI -5.63; -0.43) and MCS scores (-9.46 95% CI -11.67; -7.24). Conclusions: Among U.S. adults, SPD is associated with significantly diminished QOL above and beyond the effects of depression. Targeted interventions to mitigate the adverse effects of SPD are needed, independent of programs to address depression. C1 [Dismuke, Clara E.; Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Dismuke, Clara E.; Hernandez-Tejada, Melba A.; Egede, Leonard E.] Med Univ S Carolina, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280G,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu FU National Institute for Diabetes, Digestive and Kidney Diseases [K24 DK093699] FX Dr. Egede is supported by grant #K24 DK093699 funded by the National Institute for Diabetes, Digestive and Kidney Diseases. The manuscript represents the views of the authors and not those of the VA or NIH. Dr. Leonard E. Egede is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 29 TC 1 Z9 1 U1 1 U2 5 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, PO BOX 337, AMITYVILLE, NY 11701 USA SN 0091-2174 EI 1541-3527 J9 INT J PSYCHIAT MED JI Int. J. Psychiatr. Med. PY 2014 VL 48 IS 2 BP 135 EP 146 DI 10.2190/PM.48.2.f PG 12 WC Psychiatry SC Psychiatry GA AU5XU UT WOS:000345677700006 PM 25377154 ER PT J AU Brent, BK Holt, DJ Keshavan, MS Seidman, LJ Fonagy, P AF Brent, Benjamin K. Holt, Daphne J. Keshavan, Matcheri S. Seidman, Larry J. Fonagy, Peter TI Mentalization-based Treatment for Psychosis: Linking an Attachment-based Model to the Psychotherapy for Impaired Mental State Understanding in People with Psychotic Disorders SO ISRAEL JOURNAL OF PSYCHIATRY AND RELATED SCIENCES LA English DT Article ID BORDERLINE PERSONALITY-DISORDER; SCHIZOPHRENIA; MIND; AUTISM AB Disturbances of mentalization have been increasingly associated with the symptoms and functional impairment of people with psychotic disorders. It has been proposed that psychotherapy designed to foster self and other understanding, such as mentalization-based treatment (MBT), may play an important part in facilitating recovery from psychosis. Here, we present an attachment-based understanding of mentalization impairments. We then outline a neuropsychological model that links disruptions of mentalization associated with disturbances in the caregiving environment to the pathophysiology of psychosis in genetically at-risk individuals. This is followed by an illustration of some of the core MBT techniques for the rehabilitation of the capacity to mentalize as applied to the treatment of a patient with a psychotic disorder. C1 [Brent, Benjamin K.; Keshavan, Matcheri S.; Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Brent, Benjamin K.; Keshavan, Matcheri S.; Seidman, Larry J.] Massachusetts Mental Hlth Ctr, Boston, MA 02139 USA. [Holt, Daphne J.; Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Brent, Benjamin K.; Holt, Daphne J.; Keshavan, Matcheri S.; Seidman, Larry J.] Harvard Univ, Sch Med, Boston, MA USA. [Fonagy, Peter] UCL, Psychoanal Unit, London, England. RP Brent, BK (reprint author), Massachusetts Mental Hlth Ctr, 75 Fenwood Rd Room 618, Boston, MA 02139 USA. EM bbrent@bidmc.harvard.edu NR 37 TC 13 Z9 13 U1 3 U2 16 PU MEDIAFARM GROUP PI TEL-AVIV PA 23 ZAMENHOFF ST, TEL-AVIV, 64373, ISRAEL SN 0333-7308 J9 ISR J PSYCHIATR REL JI Isr. J. Psychiatr. Relat. Sci. PY 2014 VL 51 IS 1 BP 17 EP 24 PG 8 WC Psychiatry SC Psychiatry GA AU5XY UT WOS:000345678000003 PM 24858631 ER PT J AU Cifu, DX Hoke, KW Wetzel, PA Wares, JR Gitchel, G Carne, W AF Cifu, David X. Hoke, Kathy W. Wetzel, Paul A. Wares, Joanna R. Gitchel, George Carne, William TI Effects of hyperbaric oxygen on eye tracking abnormalities in males after mild traumatic brain injury SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE blast injury; blinded; concussion; eye tracking; hyperbaric oxygen; postconcussive syndrome; randomized; saccades; sham controlled; traumatic brain injury ID POST-CONCUSSION SYNDROME; POSTTRAUMATIC-STRESS-DISORDER; NEURAL STEM-CELLS; POSTCONCUSSION SYMPTOMS; THERAPY; RATS; PERSISTENT; MOVEMENTS; MILITARY; RECOVERY AB The effects of hyperbaric oxygen (HBO2) on eye movement abnormalities in 60 military servicemembers with at least one mild traumatic brain injury (mTBI) from combat were examined in a single-center, randomized, double-blind, sham-controlled, prospective study at the Naval Medicine Operational Training Center. During the 10 wk of the study, each subject was delivered a series of 40, once a day, hyperbaric chamber compressions at a pressure of 2.0 atmospheres absolute (ATA). At each session, subjects breathed one of three preassigned oxygen fractions (10.5%, 75%, or 100%) for 1 h, resulting in an oxygen exposure equivalent to breathing either surface air, 100% oxygen at 1.5 ATA, or 100% oxygen at 2.0 ATA, respectively. Using a standardized, validated, computerized eye tracking protocol, fixation, saccades, and smooth pursuit eye movements were measured just prior to intervention and immediately postintervention. Between-and within-groups testing of pre-and postintervention means revealed no significant differences on eye movement abnormalities and no significant main effect for HBO2 at either 1.5 ATA or 2.0 ATA equivalent compared with the sham-control. This study demonstrated that neither 1.5 nor 2.0 ATA equivalent HBO2 had an effect on postconcussive eye movement abnormalities after mTBI when compared with a sham-control. C1 [Cifu, David X.; Carne, William] Virginia Commonwealth Univ, Dept PM&R, Richmond, VA 23298 USA. [Cifu, David X.] US Dept Vet Affairs, Phys Med & Rehabil Program Off, Richmond, VA USA. [Hoke, Kathy W.; Wares, Joanna R.] Univ Richmond, Dept Math & Comp Sci, Richmond, VA 23173 USA. [Wetzel, Paul A.; Gitchel, George] Virginia Commonwealth Univ, Dept Biomed Engn, Richmond, VA 23298 USA. RP Carne, W (reprint author), Virginia Commonwealth Univ, Dept PM&R, 1223 East Marshall St, Richmond, VA 23298 USA. EM lasile@aol.com FU Air Force Medical Support Agency Medical Modernization Directorate; 711th Human Performance Wing; U.S. Navy Bureau of Medicine and Surgery; U.S. Army Medical Materiel Development Activity; Defense Advanced Research Projects Agency [N66001-09-2-206]; Defense and Veterans Brain Injury Center; U.S. Army Medical Research Acquisition Activity [W81XWH-08-2-0178]; DoD; VA Chronic Effects of Neurotrauma Consortium [W81XWH-13-2-0095] FX This material was based on work funded by the Air Force Medical Support Agency Medical Modernization Directorate and the 711th Human Performance Wing for the primary study, the U.S. Navy Bureau of Medicine and Surgery for contract funding temporary duty requirements, and the U.S. Army Medical Materiel Development Activity for end of study contract funding. Dr. Cifu's efforts were supported, in part, through a Defense Advanced Research Projects Agency grant (N66001-09-2-206) and a contract from the U.S. Army Medical Materiel Development Activity. Dr. Carne's efforts were supported, in part, through contracts from the U.S. Army Medical Materiel Development Activity and the Defense and Veterans Brain Injury Center. This work was funded primarily by the U.S. Army Medical Research Acquisition Activity (award W81XWH-08-2-0178) with support from the Defense and Veterans Brain Injury Center. Following completion of the study, additional support came from the DoD and VA Chronic Effects of Neurotrauma Consortium (grant W81XWH-13-2-0095). NR 31 TC 4 Z9 4 U1 1 U2 6 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2014 VL 51 IS 7 BP 1047 EP 1055 DI 10.1682/JRRD.2014.01.0013 PG 9 WC Rehabilitation SC Rehabilitation GA AU8JB UT WOS:000345841300004 PM 25436771 ER PT J AU Kang, HJ Dang, ABC Joshi, SK Halloran, B Nissenson, R Zhang, X Li, JA Kim, HT Liu, XH AF Kang, Heejae Dang, Alexis B. C. Joshi, Sunil K. Halloran, Bernard Nissenson, Robert Zhang, Xia Li, Jianan Kim, Hubert T. Liu, Xuhui TI Novel mouse model of spinal cord injury-induced heterotopic ossification SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE bone morphogenetic protein-2; heterotopic ossification; injury; microcomputed tomography; mouse model; muscle; rehabilitation; spinal cord injury; trauma; Veterans ID TRAUMATIC BRAIN-INJURY; RISK-FACTORS; PREVALENCE; SYSTEM; BONE AB Heterotopic ossification (HO) develops in about 20% to 30% of patients with spinal cord injury (SCI) and significantly impairs their rehabilitation. There is no effective prevention or treatment for this condition at this time. Our current understanding of its etiology and pathophysiology is limited partially due to the lack of clinically relevant animal models. In this study, we report a novel mouse model of SCI-induced HO by administering a subthreshold dose of bone morphogenetic protein (BMP)-2 to muscles in mice after SCI. Microcomputed tomography scanning showed that an intramuscular injection of 0.25 micrograms of BMP-2 causes significant HO in mice with SCI but not in control (sham surgery) mice. Our analysis of gene expression showed significantly increased BMP signaling in quadriceps following SCI, suggesting that BMP signaling may play a role in SCI-induced HO. Administering 0.25 micrograms of BMP-2 to the front arms of the mice with SCI also results in the development of significant HO but not in control mice. This suggests that SCI causes a systematic osteogenic effect, which is not limited to paralyzed limbs. This novel mouse model will serve as a powerful tool in exploring the molecular mechanisms of SCI-induced HO, which may lead to novel treatment for this disease. C1 [Kang, Heejae; Dang, Alexis B. C.; Joshi, Sunil K.; Halloran, Bernard; Nissenson, Robert; Kim, Hubert T.; Liu, Xuhui] San Francisco Dept Vet Affairs Med Ctr, San Francisco, CA USA. [Dang, Alexis B. C.; Joshi, Sunil K.; Kim, Hubert T.; Liu, Xuhui] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA USA. [Halloran, Bernard; Nissenson, Robert] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Zhang, Xia; Li, Jianan] Nanjing Med Univ, Affiliate Hosp 1, Dept Rehabil Med, Nanjing, Jiangsu, Peoples R China. RP Liu, XH (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Bldg 2,Room 639, San Francisco, CA 94121 USA. EM Liux@orthosurg.ucsf.edu FU Department of Defense [W81XWH-11-2-0189]; Department of Veterans Affairs (VA) Rehabilitation Research and Development Merit Review [RX000195]; Northern California Institute for Research and Education FX This material was based on work supported by the Department of Defense (grant W81XWH-11-2-0189), Department of Veterans Affairs (VA) Rehabilitation Research and Development Merit Review (grant RX000195), and the Northern California Institute for Research and Education. We thank Drs. Olla Larm and Lars Adolfsson (ExThera AB; Stockholm, Sweden) for their kind gift of heparin-chitosan hydrogel. NR 20 TC 2 Z9 3 U1 1 U2 2 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2014 VL 51 IS 7 BP 1109 EP 1117 DI 10.1682/JRRD.2014.01.0019 PG 9 WC Rehabilitation SC Rehabilitation GA AU8JB UT WOS:000345841300010 PM 25436890 ER PT J AU Kumar, M Singh, G Sharma, S Gupta, D Bansal, V Arora, V Bhat, M Srivastava, SK Sapra, S Kharbanda, S Dinda, AK Singh, H AF Kumar, Manoj Singh, Gurpal Sharma, Sapna Gupta, Dikshi Bansal, Vivek Arora, Vikas Bhat, Madhusudan Srivastava, Sandeep K. Sapra, Sameer Kharbanda, Surender Dinda, Amit K. Singh, Harpal TI Intracellular delivery of peptide cargos using iron oxide based nanoparticles: studies on antitumor efficacy of a BCL-2 converting peptide, NuBCP-9 SO NANOSCALE LA English DT Article ID CELL-PENETRATING PEPTIDES; DRUG-DELIVERY; MAGNETIC NANOPARTICLES; CANCER-CELLS; BREAST-CANCER; FAMILY PROTEINS; CONTRAST AGENTS; IN-VIVO; APOPTOSIS; CHEMOTHERAPY AB Delivering peptides into cells targeting the undruggable oncoproteins is an emerging area in cancer therapeutics. Here we report a novel nanoparticle-based delivery system that can transport therapeutic cargos to the intracellular sites without the need for a cell transduction or penetration domain (CPP). In the present study, we have used iron oxide nanoparticles to deliver an oncopeptide, NuBCP-9, targeting the BCL-2 BH3 domain. Citric acid/2-bromo 2-methylpropanoic acid (CA/BMPA)-capped SPIONs were used to immobilize and deliver the NuBCP-9 peptide to the cancer cells without any noticeable off-target effects. Our results have demonstrated that NuBCP-9-SPIONs efficiently penetrate into cancer cells and bind to its intracellular target protein BCL-2. Moreover, significant inhibition of proliferation and substantial induction of cell death were observed when cancer cells were treated with NuBCP-9-SPIONs at different time intervals. Importantly, the IC50 values for killing of breast cancer cells with NuBCP-9-SPIONs were much lower compared to cells treated with the NuBCP-9 peptide linked with a CPP (Arg-8; NuBCP-9-R8). Molecular and biochemical analyses further supported that NuBCP-9-SPIONs killed breast cancer cells by apoptosis-mediated mechanisms. Furthermore, our data demonstrated that administration of NuBCP-9-SPIONs to mice bearing Ehrlich ascites tumors (EAT) was associated with loss of tumorigenicity and extensive apoptosis in tumor tissues. Taken together, these findings show that a non-CPP-tagged peptide can be successfully delivered to undruggable intracellular oncotargets using SPIONs. C1 [Kumar, Manoj; Singh, Gurpal; Sharma, Sapna; Gupta, Dikshi; Bansal, Vivek; Singh, Harpal] Indian Inst Technol, Ctr Biomed Engn, New Delhi 110016, India. [Arora, Vikas; Sapra, Sameer] Indian Inst Technol, Dept Chem, New Delhi 110016, India. [Bhat, Madhusudan; Srivastava, Sandeep K.; Dinda, Amit K.] All India Inst Med Sci Ansari Nagar, Dept Pathol, New Delhi 110023, India. [Kharbanda, Surender] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Singh, H (reprint author), Indian Inst Technol, Ctr Biomed Engn, New Delhi 110016, India. EM harpal2000@yahoo.com OI Sapra, Sameer/0000-0002-1778-2884 FU Department of Science and Technology, Govt. of India FX The authors gratefully acknowledge the Department of Science and Technology, Govt. of India for financial support. NR 60 TC 1 Z9 3 U1 0 U2 10 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 23 BP 14473 EP 14483 DI 10.1039/c4nr04504a PG 11 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA AT5QR UT WOS:000344997600051 PM 25340469 ER PT B AU Hasturk, H Cugini, M AF Hasturk, Hatice Cugini, MaryAnn BE Giannobile, WV Lang, NP Tonetti, MS TI Examiner Standardization and Calibration for Oral and Periodontal Regenerative Studies SO OSTEOLOGY GUIDELINES FOR ORAL AND MAXILLOFACIAL REGENERATION: CLINICAL RESEARCH LA English DT Article; Book Chapter ID RESONANCE FREQUENCY-ANALYSIS; DAMPING CAPACITY ASSESSMENT; BEAM COMPUTED-TOMOGRAPHY; PERI-IMPLANT DISEASES; OUTCOME MEASUREMENTS; INTRABONY DEFECTS; INFRABONY DEFECTS; ATTACHED GINGIVA; DENTAL IMPLANT; CLINICAL-TRIAL C1 [Hasturk, Hatice; Cugini, MaryAnn] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA 02135 USA. [Hasturk, Hatice] Forsyth Inst, Ctr Clin & Translat Res, Cambridge, MA 02135 USA. [Cugini, MaryAnn] Forsyth Inst, Inst Review Board, Cambridge, MA 02135 USA. RP Hasturk, H (reprint author), Forsyth Inst, Dept Appl Oral Sci, 245 First St,Suite 1757, Cambridge, MA 02135 USA. EM hhasturk@forsyth.org; mcugini@forsyth.org NR 87 TC 0 Z9 0 U1 0 U2 0 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA BN 978-1-85097-274-7 PY 2014 BP 97 EP 120 PG 24 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BB7NU UT WOS:000345803000009 ER PT B AU Kantarci, A AF Kantarci, Alpdogan BE Giannobile, WV Lang, NP Tonetti, MS TI Biomarkers and Molecular Biological Methods in Diagnostic, Preventive, and Regenerative Dental Research SO OSTEOLOGY GUIDELINES FOR ORAL AND MAXILLOFACIAL REGENERATION: CLINICAL RESEARCH LA English DT Article; Book Chapter ID LINKED-IMMUNOSORBENT-ASSAY; SURROGATE END-POINTS; PORPHYROMONAS-GINGIVALIS; SUBGINGIVAL PLAQUE; PERIODONTAL PATHOGENS; BACTEROIDES-FORSYTHUS; TREPONEMA-DENTICOLA; QUANTITATIVE ASSAY; IMMUNOGLOBULIN-G; COATED TUBES C1 Forsyth Inst, Dept Appl Oral Sci, Ctr Periodontol, Cambridge, MA 02142 USA. RP Kantarci, A (reprint author), Forsyth Inst, Dept Appl Oral Sci, Ctr Periodontol, 245 First St, Cambridge, MA 02142 USA. EM akantarci@forsyth.org NR 40 TC 0 Z9 0 U1 0 U2 0 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA BN 978-1-85097-274-7 PY 2014 BP 159 EP 174 PG 16 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BB7NU UT WOS:000345803000013 ER PT J AU Iverson, KM McLaughlin, KA Adair, KC Monson, CM AF Iverson, Katherine M. McLaughlin, Katie A. Adair, Kathryn C. Monson, Candice M. TI Anger-Related Dysregulation as a Factor Linking Childhood Physical Abuse and Interparental Violence to Intimate Partner Violence Experiences SO VIOLENCE AND VICTIMS LA English DT Article DE domestic violence; childhood maltreatment; emotion dysregulation; anger; gender ID TACTICS-SCALES CTS2; EMOTION DYSREGULATION; FAMILY VIOLENCE; SEXUAL REVICTIMIZATION; GENDER-DIFFERENCES; DATING VIOLENCE; HEALTH; RISK; VICTIMIZATION; WOMEN AB Objective: Childhood family violence exposure is associated with increased risk for experiencing intimate partner violence (IPV) in adulthood, but the mechanisms underlying this relationship remain inadequately understood. Difficulties with emotion regulation may be one factor that helps to explain this relationship. Method: Childhood physical abuse and interparental violence, as well as subsequent IPV experiences, were assessed in a large sample of young adults (N = 670). Several indicators of anger-related dysregulation were also assessed. Structural equation modeling was used to create a latent variable of anger-related dysregulation, which was examined as a potential mediator of the associations between childhood family violence exposure and IPV. Results: Childhood physical abuse and interparental violence were associated with greater physical, sexual, and emotional IPV victimization. Childhood physical abuse and interparental violence were also associated with anger-related dysregulation, which was positively associated with all three types of IPV experiences. Anger-related dysregulation fully mediated the association between witnessing interparental violence and physical IPV. Anger-related dysregulation partially mediated the association between witnessing interparental violence and psychological IPV and the associations of childhood physical abuse with all three forms of IPV. These associations were consistent across gender. Conclusions: Interventions aimed at reducing IPV risk among survivors of childhood family violence may benefit from including techniques to target anger-related emotion regulation skills. C1 [Iverson, Katherine M.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02215 USA. [McLaughlin, Katie A.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Adair, Kathryn C.] Univ N Carolina, Chapel Hill, NC USA. [Monson, Candice M.] Ryerson Univ, Toronto, ON, Canada. RP Iverson, KM (reprint author), VA Boston Healthcare Syst, WHSD 116B 3, 150 South Huntington Ave, Boston, MA 02130 USA. EM Katherine.Iverson@va.gov FU NIMH NIH HHS [K01 MH092526] NR 57 TC 3 Z9 3 U1 8 U2 23 PU SPRINGER PUBLISHING CO PI NEW YORK PA 11 WEST 42ND STREET, NEW YORK, NY 10036 USA SN 0886-6708 EI 1945-7073 J9 VIOLENCE VICTIMS JI Violence Vict. PY 2014 VL 29 IS 4 BP 564 EP 578 DI 10.1891/0886-6708.VV-D-12-00125 PG 15 WC Criminology & Penology SC Criminology & Penology GA AU5ZA UT WOS:000345680700002 PM 25199386 ER PT S AU Blumrosen, G Abazari, A Golberg, A Tonner, M Yarmush, ML AF Blumrosen, Gaddi Abazari, Alireza Golberg, Alexander Tonner, Mehmet Yarmush, Martin L. GP IEEE TI Efficient Procedure and Methods to Determine Critical Electroporation Parameters SO 2014 IEEE 27TH INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS (CBMS) SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 27th IEEE International Symposium on Computer-Based Medical Systems (CBMS) CY MAY 27-29, 2014 CL Icahn Sch Med, New York, NY SP IEEE, IEEE Comp Soc, Texas Tech Univ, IBMWATSON HO Icahn Sch Med DE Electroporation; clustering; Image processing; Light Microscopy; Biological system modeling ID IRREVERSIBLE ELECTROPORATION; FLUORESCENT CELLS; ELECTRIC-FIELDS; ELECTROPERMEABILIZATION; MICROSCOPY; THRESHOLD; TRACKING; TRIAL; DRUG AB Controlling electroporation and determination of its design parameters govern the performance in many electroporation applications in the fields of medicine, biology, and food industry. This work provides an enhanced high throughput signal processing method to enable non-expert, objective, automatic and fast analysis of large datasets of microscopic images of high throughput electroporation experiments. This can enable optimal design of vital electroporation parameters including the optimal thresholds for the electric field strength, and the optimal number of pulses. In this work the non-expert visualization platform and the methods are described, and implemented on normal dermal human fibroblasts cell culture. C1 [Blumrosen, Gaddi] Tel Aviv Univ, Dept Comp Sci, IL-69978 Tel Aviv, Israel. [Abazari, Alireza; Golberg, Alexander; Tonner, Mehmet; Yarmush, Martin L.] Shriners Burns Inst, Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg,Ctr Engn Med, Boston, MA 02114 USA. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Pisacataway, NJ 08854 USA. RP Blumrosen, G (reprint author), Tel Aviv Univ, Dept Comp Sci, IL-69978 Tel Aviv, Israel. EM gaddi.b@gmail.com NR 22 TC 2 Z9 2 U1 1 U2 4 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2372-9198 BN 978-1-4799-4435-4 J9 COMP MED SY PY 2014 BP 314 EP 318 DI 10.1109/CBMS.2014.18 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Engineering, Biomedical SC Computer Science; Engineering GA BB6ZP UT WOS:000345222200062 ER PT S AU Gudnason, J Mehta, DD Quatieri, TF AF Gudnason, Jon Mehta, Daryush D. Quatieri, Thomas F. GP IEEE TI CLOSED PHASE ESTIMATION FOR INVERSE FILTERING THE ORAL AIRFLOW WAVEFORM SO 2014 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH AND SIGNAL PROCESSING (ICASSP) SE International Conference on Acoustics Speech and Signal Processing ICASSP LA English DT Proceedings Paper CT IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP) CY MAY 04-09, 2014 CL Florence, ITALY SP IEEE DE Inverse filtering; glottal airflow; Rothenberg mask; glottal closure instant detection ID GLOTTAL CLOSURE; SPEECH AB Glottal closed phase estimation during speech production is critical to inverse filtering and, although addressed for radiated acoustic pressure analysis, must be better understood for the analysis of the oral airflow volume velocity signal that provides important properties of healthy and disordered voices. This paper compares the estimation of the closed phase from the acoustic speech signal and the oral airflow waveform recorded using a pneumotachograph mask. Results are presented for ten adult speakers with normal voices who sustained a set of vowels at a comfortable pitch and loudness. With electroglottography as reference, the identification rate and accuracy of glottal closure instants for the oral airflow are 96.8 % and 0.28 ms, whereas these metrics are 99.4 % and 0.10 ms for the acoustic signal. We conclude that glottal closure detection is adequate for close phase inverse filtering but that improvements to detection of glottal opening instants on the oral airflow signal are warranted. C1 [Gudnason, Jon] Reykyavik Univ, Ctr Anal & Design Intelligent Agents, Menntavegur 1, Iceland. [Mehta, Daryush D.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Mehta, Daryush D.; Quatieri, Thomas F.] MIT, Lincoln Lab, Lexington, MA 02173 USA. RP Gudnason, J (reprint author), Reykyavik Univ, Ctr Anal & Design Intelligent Agents, Menntavegur 1, Iceland. EM jg@ru.is; daryush.mehta@alum.mit.edu; quatieri@ll.mit.edu FU Assistant Secretary of Defense for Research & Engineering under Air Force [FA8721-05-C-0002]; National Institutes of Health; National Institute on Deafness and Other Communication Disorders [R33 DC011588] FX The Lincoln Laboratory portion of this work is sponsored by the Assistant Secretary of Defense for Research & Engineering under Air Force Contract FA8721-05-C-0002. Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the United States Government. Also supported by the National Institutes of Health National Institute on Deafness and Other Communication Disorders under grant R33 DC011588. NR 18 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1520-6149 BN 978-1-4799-2893-4 J9 INT CONF ACOUST SPEE PY 2014 PG 5 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BB5BJ UT WOS:000343655300186 ER PT S AU Luessi, M Hamalainen, MS Solo, V AF Luessi, Martin Haemaelaeinen, Matti S. Solo, Victor GP IEEE TI VECTOR l(0) LATENT-SPACE PRINCIPAL COMPONENT ANALYSIS SO 2014 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH AND SIGNAL PROCESSING (ICASSP) SE International Conference on Acoustics Speech and Signal Processing ICASSP LA English DT Proceedings Paper CT IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP) CY MAY 04-09, 2014 CL Florence, ITALY SP IEEE DE principal component analysis; PCA; minorization-maximization; penalized likelihood; sparsity; l0; MEG; EEG; source localization AB Principal component analysis (PCA) is a widely used signal processing technique. Instead of performing PCA in the data space, we consider the problem of sparse PCA in a potentially higher dimensional latent space. To do so, we zero-out groups of variables using vector l(0) regularization. The estimation is based on the maximization of the penalized log-likelihood, for which we develop an efficient coupled expectation-maximization (EM) - minorization-maximization (MM) algorithm. For the special case when the latent-and observation space are identical, our method corresponds to an existing vector l(0) PCA method, which we verify using simulations. The proposed method can also be utilized for penalized linear regression and we use simulations to demonstrate superior estimation performance. As an example of a practical application, we use our method to localize cortical activity from magnetoencephalography (MEG) data. C1 [Luessi, Martin; Haemaelaeinen, Matti S.; Solo, Victor] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Luessi, M (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1520-6149 BN 978-1-4799-2893-4 J9 INT CONF ACOUST SPEE PY 2014 PG 5 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BB5BJ UT WOS:000343655304051 ER PT J AU Sharma, A Garg, A Borer, JS Krishnamoorthy, P Garg, J Lavie, CJ Arbab-Zadeh, A Mukherjee, D Ahmad, H Lichstein, E AF Sharma, Abhishek Garg, Akash Borer, Jeffrey S. Krishnamoorthy, Parasuram Garg, Jalaj Lavie, Carl J. Arbab-Zadeh, Armin Mukherjee, Debabrata Ahmad, Hasan Lichstein, Edgar TI Role of Oral Factor Xa Inhibitors after Acute Coronary Syndrome SO CARDIOLOGY LA English DT Article DE Acute coronary syndrome; Factor Xa; Coagulation pathway ID ELEVATION MYOCARDIAL-INFARCTION; MOLECULAR-WEIGHT HEPARIN; UNFRACTIONATED HEPARIN; ANTIPLATELET THERAPY; CONTROLLED-TRIAL; IN-VIVO; UNSTABLE ANGINA; POOLED ANALYSIS; ARTERY-DISEASE; DOUBLE-BLIND AB Despite an early invasive strategy and the use of dual antiplatelet therapy, patients with acute coronary syndrome (ACS) continue to be at substantial risk for recurrent ischemic events. It is believed that this risk is, at least in part, due to an intrinsic coagulation pathway that remains activated for a prolonged period after ACS. Earlier studies using warfarin showed a reduction in ischemic events, but the overall benefits were offset by increased bleeding complications. Recently, there has been increased interest in the potential role of new oral anticoagulants, some of which target factor Xa, after ACS. Factor Xa is important for the coagulation pathway and also plays a role in cellular proliferation and inflammation. It may thus be an attractive target for therapeutic intervention in ACS. Recently, various oral factor Xa inhibitors have been studied as potential treatment options for ACS. This review will focus on currently available data to evaluate the possible role of factor Xa inhibitors in the management of patients with ACS. (C) 2014 S. Karger AG, Basel C1 [Sharma, Abhishek] Suny Downstate Med Ctr, Div Cardiovasc Med, New York, NY USA. [Borer, Jeffrey S.] Suny Downstate Med Ctr, Howard Gilman Inst Heart Valve Dis, New York, NY USA. [Borer, Jeffrey S.] Suny Downstate Med Ctr, Schiavone Inst Cardiovasc Translat Res, New York, NY USA. [Garg, Akash] Mt Sinai Sch Med, James J Peters VA Med Ctr, Dept Med, New York, NY USA. [Lichstein, Edgar] Maimonides Hosp, Dept Med, New York, NY USA. [Krishnamoorthy, Parasuram] Mt Sinai Englewood Hosp & Med Ctr Englewood, Dept Internal Med, Englewood, CO USA. [Garg, Jalaj] New York Med Coll, Dept Internal Med, Westchester Med Ctr, Valhalla, NY 10595 USA. [Ahmad, Hasan] New York Med Coll, Westchester Med Ctr, Div Cardiol, Valhalla, NY 10595 USA. [Lavie, Carl J.] Univ Queensland, Sch Med, John Ochsner Heart & Vasc Inst, Dept Cardiovasc Dis,Ochsner Clin Sch, New Orleans, LA USA. [Lavie, Carl J.] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Dept Prevent Med, Baton Rouge, LA USA. [Arbab-Zadeh, Armin] Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD USA. [Mukherjee, Debabrata] Texas Tech Univ, Div Cardiol, Lubbock, TX 79409 USA. RP Sharma, A (reprint author), 240 78th St Apt 2R, Brooklyn, NY 11209 USA. EM abhisheksharma4mamc@gmail.com RI Lavie, Carl/A-6014-2011; OI Krishnamoorthy, Parasuram/0000-0002-4560-7346 NR 51 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2014 VL 129 IS 4 BP 224 EP 232 DI 10.1159/000368747 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AU2KL UT WOS:000345447000005 PM 25402219 ER PT J AU Tian, YL Zhang, XL Li, YY Shoup, TM Teng, X Elmaleh, DR Moore, A Ran, CZ AF Tian, Yanli Zhang, Xueli Li, Yuyan Shoup, Timothy M. Teng, Xin Elmaleh, David R. Moore, Anna Ran, Chongzhao TI Crown ethers attenuate aggregation of amyloid beta of Alzheimer's disease SO CHEMICAL COMMUNICATIONS LA English DT Article ID PROBING MASS-SPECTROMETRY; MOLECULAR RECOGNITION; TRANSGENIC MICE; FIBRILS; PEPTIDE; BINDING; COMPLEXES; MECHANISM; OLIGOMERS AB In this report, we reasoned that non-covalent modification of amyloid beta (Ab) by crown ethers could inhibit its aggregation. We demonstrated that PiB-C, a conjugate PiB and crown ether, could significantly reduce the aggregation in vitro. Additionally, two-photon imaging showed that PiB-C could efficiently label Ab plaques and CAAs in AD mice. C1 [Tian, Yanli; Zhang, Xueli; Li, Yuyan; Moore, Anna; Ran, Chongzhao] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Imaging Lab,AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Tian, Yanli] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Parasitol, Guangzhou 510275, Guangdong, Peoples R China. [Zhang, Xueli; Li, Yuyan] China Pharmaceut Univ, Sch Pharm, Nanjing, Jiangsu, Peoples R China. [Zhang, Xueli] Southeast Univ, ZhongDa Hosp, Dept Pharm, Nanjing, Jiangsu, Peoples R China. [Shoup, Timothy M.; Teng, Xin; Elmaleh, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging,Dept Radiol, Boston, MA USA. RP Moore, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Imaging Lab,AA Martinos Ctr Biomed Imaging, Bldg 75, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu; cran@nmr.mgh.harvard.edu FU [K25AG036760] FX This work was supported by a K25AG036760 award to C.R. The authors would also like to thank Pamela Pantazopoulos, B.S. for proofreading this manuscript. NR 36 TC 8 Z9 8 U1 1 U2 18 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 EI 1364-548X J9 CHEM COMMUN JI Chem. Commun. PY 2014 VL 50 IS 99 BP 15792 EP 15795 DI 10.1039/c4cc06029f PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA AU0IB UT WOS:000345305600034 PM 25372154 ER PT J AU Creaney, J Segal, A Olsen, N Dick, IM Musk, AW Skates, SJ Robinson, BW AF Creaney, Jenette Segal, Amanda Olsen, Nola Dick, Ian M. Musk, A. W. (Bill) Skates, Steven J. Robinson, Bruce W. TI Pleural Fluid Mesothelin as an Adjunct to the Diagnosis of Pleural Malignant Mesothelioma SO DISEASE MARKERS LA English DT Article ID SOLUBLE MESOTHELIN; SERUM MESOTHELIN; EFFUSIONS; AUSTRALIA; CYTOLOGY; MARKERS AB Rationale. The diagnosis of pleural malignant mesothelioma (MM) by effusion cytology may be difficult and is currently controversial. Effusion mesothelin levels are increased in patients with MM but the clinical role of this test is uncertain. Objectives. To determine the clinical value of measuring mesothelin levels in pleural effusion supernatant to aid diagnosis of MM. Methods and Measurements. Pleural effusion samples were collected prospectively from 1331 consecutive patients. Mesothelin levels were determined by commercial ELISA in effusions and their relationship to concurrent pathology reporting and final clinical diagnosis was determined. Results. 2156 pleural effusion samples from 1331 individuals were analysed. The final clinical diagnosis was 183 MM, 436 non-MM malignancy, and 712 nonmalignant effusions. Effusion mesothelin had a sensitivity of 67% for MM at 95% specificity. Mesothelin was elevated in over 47% of MM cases in effusions obtained before definitive diagnosis of MM was established. In the setting of inconclusive effusion cytology, effusion mesothelin had a positive predictive value of 79% for MM and 94% for malignancy. Conclusions. A mesothelin-positive pleural effusion, irrespective of the identification of malignant cells, indicates the likely presence of malignancy and adds weight to the clinical rationale for further investigation to establish a malignant diagnosis. C1 [Creaney, Jenette; Dick, Ian M.; Musk, A. W. (Bill); Robinson, Bruce W.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. [Creaney, Jenette; Dick, Ian M.; Musk, A. W. (Bill); Robinson, Bruce W.] Univ Western Australia, Natl Ctr Asbestos Related Dis, Nedlands, WA 6009, Australia. [Segal, Amanda] Queen Elizabeth II Med Ctr, PathWest Lab Med, Nedlands, WA 6009, Australia. [Olsen, Nola; Musk, A. W. (Bill); Robinson, Bruce W.] Sir Charles Gairdner Hosp, Dept Resp Med, Nedlands, WA 6009, Australia. [Olsen, Nola; Musk, A. W. (Bill)] Univ Western Australia, Sch Populat Hlth, Crawley, WA 6009, Australia. [Skates, Steven J.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Skates, Steven J.] Harvard Univ, Sch Med, Boston, MA USA. RP Creaney, J (reprint author), Univ Western Australia, Sch Med & Pharmacol, M503,23 Stirling Highway, Perth, WA 6009, Australia. EM jenette.creaney@uwa.edu.au FU NHMRC; Insurance Commission of Western Australia FX The authors acknowledge the staff of Path West Laboratory Medicine for assistance in collection of samples. The authors thank Hanne Dare, Justine Leon, and Yvonne Demelker for technical assistance with this study. This study was supported in part by the NHMRC and the Insurance Commission of Western Australia. The authors also acknowledge the participants in this study. NR 26 TC 1 Z9 1 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 0278-0240 EI 1875-8630 J9 DIS MARKERS JI Dis. Markers PY 2014 AR 413946 DI 10.1155/2014/413946 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA AU4DY UT WOS:000345560600001 ER PT J AU Jiang, FG Deng, Y Yeh, CK Sun, YY AF Jiang, Fuguang Deng, Ying Yeh, Chih-Ko Sun, Yuyu TI Quaternized chitosans bind onto preexisting biofilms and eradicate pre-attached microorganisms SO JOURNAL OF MATERIALS CHEMISTRY B LA English DT Article ID CATHETER-RELATED INFECTIONS; GRAM-NEGATIVE BACTERIA; LACTIC-ACID BACTERIA; TRIMETHYL CHITOSAN; NOSOCOMIAL INFECTIONS; ANTIMICROBIAL ACTIVITY; UNITED-STATES; DERIVATIVES; RESISTANCE; MEMBRANE AB Quaternized chitosans, N,N,N-trimethylchitosan (TMC), with different degrees of quaternization were synthesized by reacting methyl iodide with chitosan. The reaction was confirmed by FT-IR and H-1-NMR characterization. Antimicrobial assay showed that the prepared TMC had potent biocidal effects against planktonic Gram-positive bacteria Staphylococcus epidermidis, Gram-negative bacteria Escherichia coli, and yeast Candida albicans. Bacterial and fungal biofilms were formed on poly(methyl methacrylate) (PMMA) films and then treated with TMC aqueous solution. Zeta potential measurement suggested that TMC bonded onto the preexisting biofilms. Biofilm-binding kinetics was evaluated in UV studies using phenyl group-labeled TMC as a model compound, which revealed that quaternized chitosans bonded onto the preexisting biofilms rapidly. Colony-forming unit (CFU) determination and SEM, confocal laser scanning microscopy (CLSM) and fluorescence microscopy studies demonstrated that the bonded TMC had powerful biocidal activities to eradicate the pre-attached bacterial and fungal cells in the preexisting biofilms. The biocompatibility of the TMC samples with rat skin fibroblast cells was evaluated in the MTT assay. C1 [Jiang, Fuguang; Sun, Yuyu] Univ Massachusetts Lowell, Dept Chem, Lowell, MA 01854 USA. [Deng, Ying] Univ S Dakota, Biomed Engn Program, Sioux Falls, SD 57107 USA. [Yeh, Chih-Ko] Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, Geriatr Res Educ & Clin Ctr, Audie L Murphy Div,South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Sun, YY (reprint author), Univ Massachusetts Lowell, Dept Chem, Lowell, MA 01854 USA. EM ying.deng@usd.edu; yeh@uthscsa.edu; yuyu_sun@uml.edu FU NIDCR, NIH [R01 DE021084]; VA Merit Review [1I01BX001103-01A1] FX This study was supported by NIDCR, NIH (R01 DE021084) and VA Merit Review (1I01BX001103-01A1). NR 50 TC 4 Z9 4 U1 0 U2 10 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2050-750X EI 2050-7518 J9 J MATER CHEM B JI J. Mat. Chem. B PY 2014 VL 2 IS 48 BP 8518 EP 8527 DI 10.1039/c4tb01131g PG 10 WC Materials Science, Biomaterials SC Materials Science GA AU3QT UT WOS:000345529400008 PM 25984341 ER PT J AU Patel, H Chuckowree, I Coxhead, P Guille, M Wang, MH Zuckermann, A Williams, RSB Librizzi, M Paranal, RM Bradner, JE Spencer, J AF Patel, Hiren Chuckowree, Irina Coxhead, Peter Guille, Matthew Wang, Minghua Zuckermann, Alexandra Williams, Robin S. B. Librizzi, Mariangela Paranal, Ronald M. Bradner, James E. Spencer, John TI Synthesis of hybrid anticancer agents based on kinase and histone deacetylase inhibitors SO MEDCHEMCOMM LA English DT Article ID TYROSINE KINASE; HDAC INHIBITORS; CANCER CELLS; ACID; ANGIOGENESIS; DESIGN; BREAST; GROWTH; SELECTIVITY; MO(CO)(6) AB Fragments based on the VEGFR2i Semaxanib (SU5416, (vascular endothelial growth factor receptor-2 inhibitor) and the HDACi (histone deacetylase inhibitor) SAHA (suberanilohydroxamic acid) have been merged to form a range of low molecular weight dual action hybrids. Vindication of this approach is provided by SAR, docking studies, in vitro cancer cell line and biochemical enzyme inhibition data as well as in vivo Xenopus data for the lead molecule (Z)-N1-(3-((1H-pyrrol-2-yl) methylene)-2-oxoindolin-5-yl)N8- hydroxyoctanediamide 6. C1 [Patel, Hiren; Chuckowree, Irina; Spencer, John] Univ Greenwich, Sch Sci Medway, Chatham ME4 4TB, Kent, England. [Chuckowree, Irina; Spencer, John] Univ Sussex, Sch Life Sci, Dept Chem, Brighton BN1 9QJ, E Sussex, England. [Coxhead, Peter; Guille, Matthew] Univ Portsmouth, Sch Biol Sci, Portsmouth PO1 2DY, Hants, England. [Wang, Minghua] Univ Toronto, Terrence Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada. [Zuckermann, Alexandra; Williams, Robin S. B.] Royal Holloway Univ London, Sch Biol Sci, Ctr Biomed Sci, Egham TW20 0EX, Surrey, England. [Librizzi, Mariangela] Univ Palermo, Dipartimento STEBICEF, I-90128 Palermo, Italy. [Paranal, Ronald M.; Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Spencer, J (reprint author), Univ Greenwich, Sch Sci Medway, Chatham ME4 4TB, Kent, England. EM j.spencer@sussex.ac.uk RI spencer, john/C-2156-2008; Williams, Robin/G-6807-2011 OI spencer, john/0000-0001-5231-8836; NR 40 TC 6 Z9 6 U1 0 U2 6 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-2503 EI 2040-2511 J9 MEDCHEMCOMM JI MedChemComm PY 2014 VL 5 IS 12 BP 1829 EP 1833 DI 10.1039/c4md00211c PG 5 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA AU2NP UT WOS:000345455600006 ER PT B AU Johansen, KL Painter, P AF Johansen, Kirsten L. Painter, Patricia BE ByhamGray, LD Burrowes, JD Chertow, GM TI Physical Activity and Exercise SO NUTRITION IN KIDNEY DISEASE, 2ND EDITION SE Nutrition and Health Series LA English DT Article; Book Chapter DE Physical activity; Exercise; Chronic kidney disease; Reconditioning; Walking; End-stage renal disease; Dialysis ID STAGE RENAL-DISEASE; CHRONIC KIDNEY-DISEASE; AMERICAN-HEART-ASSOCIATION; QUALITY-OF-LIFE; HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS; AMBULATORY PATIENTS; OLDER-ADULTS; PERITONEAL-DIALYSIS; TRANSPLANT PATIENTS C1 [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA USA. [Painter, Patricia] Univ Utah, Coll Hlth, Dept Phys Therapy, Salt Lake City, UT 84108 USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, 4150 Clement St, San Francisco, CA 94121 USA. EM kirsten.johansen@ucsf.edu; trish.painter@hsc.utah.edu NR 75 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 BN 978-1-62703-685-6; 978-1-62703-684-9 J9 NUTR HEALTH SER JI Nutr. Health Ser. PY 2014 BP 271 EP 287 DI 10.1007/978-1-62703-685-6_16 D2 10.1007/978-1-62703-685-6 PG 17 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA BB6QG UT WOS:000344931000019 ER PT J AU Weinstein, L Perez-Rodriguez, MM Siever, L AF Weinstein, Lissa Mercedes Perez-Rodriguez, M. Siever, Larry TI Personality Disorders, Attachment and Psychodynamic Psychotherapy SO PSYCHOPATHOLOGY LA English DT Article DE Personality disorders; Attachment patterns; Psychodynamic psychotherapy; Interpersonal functioning ID MENTALIZATION-BASED TREATMENT; INTRANASAL OXYTOCIN; INSECURE ATTACHMENT; BORDERLINE TRAITS; SOCIAL ATTACHMENT; MATERNAL BRAIN; NEUROBIOLOGY; ADULTS; STRESS; SCHIZOPHRENIA AB While attachment has been a fruitful and critical concept in understanding enduring individual templates for interpersonal relationships, it does not have a well-understood relationship to personality disorders, where impairment of interpersonal functioning is paramount. Despite the recognition that attachment disturbances do not simply reflect nonoptimal caretaking environments, the relationship of underlying temperamental factors to these environmental insults has not been fully explored. In this paper we provide an alternate model for the role of neurobiological temperamental factors, including brain circuitry and neuropeptide modulation, in mediating social cognition and the internalization and maintenance of attachment patterns. The implications of these altered attachment patterns on personality disorders and their neurobiological and environmental roots for psychoanalytically based treatment models designed to ameliorate difficulties in interpersonal functioning through the medium of increased access to mature forms of mentalization is discussed. (C) 2014 S. Karger AG, Basel C1 [Weinstein, Lissa] CUNY City Coll, Doctoral Program Clin Psychol, New York, NY 10031 USA. [Weinstein, Lissa] CUNY, Grad Ctr, New York, NY USA. [Mercedes Perez-Rodriguez, M.; Siever, Larry] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Mercedes Perez-Rodriguez, M.; Siever, Larry] Mental Hlth Patient Care Ctr, Bronx, NY USA. [Mercedes Perez-Rodriguez, M.; Siever, Larry] James J Peters Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. [Mercedes Perez-Rodriguez, M.] Autonomous Univ Madrid, Fdn Jimenez Diaz Hosp, CIBERSAM, E-28049 Madrid, Spain. RP Weinstein, L (reprint author), CUNY City Coll, 160 Convent Ave, New York, NY 10031 USA. EM lissa_weinstein@hotmail.com RI Perez Rodriguez, Maria/B-9410-2013 OI Perez Rodriguez, Maria/0000-0001-5137-1993 NR 110 TC 1 Z9 1 U1 3 U2 15 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0254-4962 EI 1423-033X J9 PSYCHOPATHOLOGY JI Psychopathology PY 2014 VL 47 IS 6 BP 425 EP 436 DI 10.1159/000366135 PG 12 WC Psychiatry SC Psychiatry GA AU5QJ UT WOS:000345661400010 PM 25376756 ER PT J AU Brachtel, EF Smith, BL Tearney, GJ Kang, D AF Brachtel, Elena F. Smith, Barbara L. Tearney, Guillermo J. Kang, Dongkyun TI Spectrally Encoded Confocal Microscopy for Guiding Lumpectomy SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article C1 [Brachtel, Elena F.; Smith, Barbara L.; Tearney, Guillermo J.; Kang, Dongkyun] Massachusetts Gen Hosp, Boston, MA 02474 USA. RP Kang, D (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02474 USA. EM dkang@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 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 573851 DI 10.1155/2014/573851 PG 2 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA AU2AK UT WOS:000345418300001 ER PT J AU Jones, NC Nazarian, RM Duncan, LM Wilbur, DC AF Jones, Nicholas C. Nazarian, Rosalynn M. Duncan, Lyn M. Wilbur, David C. TI MGH Whole Slide Imaging Teleconsultation Practice in Dermatopathology SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article C1 [Jones, Nicholas C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jones, NC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM ncjones@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 347147 DI 10.1155/2014/347147 PG 1 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA AU2AE UT WOS:000345417700001 ER PT J AU Ohnishi, T Tanaka, T Nakamura, Y Hashimoto, N Haneishi, H Taylor, J Snuderl, M Yagi, Y AF Ohnishi, Takashi Tanaka, Takuya Nakamura, Yuka Hashimoto, Noriaki Haneishi, Hideaki Taylor, Jennie Snuderl, Matija Yagi, Yukako TI Connection and Deformation of Pathological Images via a Macro Image for Comparing Different Modality Images of Brain Tumor SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article C1 [Ohnishi, Takashi; Hashimoto, Noriaki; Haneishi, Hideaki] Chiba Univ, Ctr Frontier Med Engn, Chiba 2638522, Japan. [Tanaka, Takuya] Chiba Univ, Dept Med Syst Engn, Chiba 2638522, Japan. [Nakamura, Yuka] Chiba Univ, Grad Sch Engn, Chiba 2638522, Japan. [Taylor, Jennie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Snuderl, Matija] NYU, Langone Med Ctr, New York, NY 10016 USA. [Yagi, Yukako] Massachusetts Gen Hosp, Pathol Imaging & Commun Technol PICT Ctr, Boston, MA 02114 USA. [Yagi, Yukako] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Ohnishi, T (reprint author), Chiba Univ, Ctr Frontier Med Engn, Chiba 2638522, Japan. EM t-ohnishi@chiba-u.jp OI Snuderl, Matija/0000-0003-0752-0917 FU JSPS [25560189] FX This work was partly supported by JSPS Grants-in-Aid for Challenging Exploratory Research Grant no. 25560189. Authors acknowledge Dr. Tracy Batechlor, Dr. Elizabeth Gerstner, and Dr. Christine Lu-Emerson for their contribution to the project. NR 0 TC 0 Z9 0 U1 0 U2 1 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 368951 DI 10.1155/2014/368951 PG 3 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA AU2AH UT WOS:000345418000001 ER PT J AU Shang, WH Lu, WD Han, M Qiao, JP AF Shang, Weihu Lu, Weidong Han, Mei Qiao, Jinping TI The Interactions of Anticancer Agents with Tea Catechins: Current Evidence from Preclinical Studies SO ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY LA English DT Article DE Drug interactions; EGCG; pharmacodynamics; pharmacokinetics; tea catechins ID BREAST-CANCER CELLS; GREEN TEA; TUMOR-GROWTH; EPIGALLOCATECHIN-3-GALLATE EGCG; BLACK TEA; IN-VITRO; POLYPHENOLS; MECHANISMS; PREVENTION; (-)-EPIGALLOCATECHIN-3-GALLATE AB Tea catechins exhibit a broad range of pharmacological activities that impart beneficial effects on human health. Epigallocatechin-3-gallate (EGCG), one of the major tea catechins, has been widely associated with cancer prevention and treatment. In addition, tea catechins in combination with anticancer drugs are being evaluated as a new cancer treatment strategy. However, the interactions of anticancer drugs with tea catechins are largely unknown. Accumulated data indicate significant interactions between anticancer drugs and tea catechins, such as synergistic tumor inhibition or antagonist activity. Therefore, it is critical to understand comprehensively the effects of tea catechins on anticancer drugs. Focusing on evidence from preclinical studies, this paper will review the interactions between anticancer drugs and tea catechins, including pharmacodynamics and pharmacokinetics effects. We hope that by detailing the interactions between anticancer drugs and tea catechins, more attention will be directed to this important therapeutic combination in the future. C1 [Shang, Weihu; Han, Mei; Qiao, Jinping] Beijing Normal Univ, Coll Chem, Key Lab Radiopharmaceut Chem, Minist Educ, Beijing 100875, Peoples R China. [Lu, Weidong] Harvard Univ, Sch Med, Dana Farber Canc Inst, Leonard P Zakim Ctr, Boston, MA 02115 USA. RP Han, M (reprint author), Beijing Normal Univ, Coll Chem, Key Lab Radiopharmaceut Chem, Minist Educ, 19 Xin Jie Kou Wai Ave, Beijing 100875, Peoples R China. EM hanmei@bnu.edu.cn; qiao_jinping@bnu.edu.cn RI Lu, Weidong/C-3844-2008 OI Lu, Weidong/0000-0003-2838-6307 FU National Key Technology RD Program [2008BAI49B04]; China National Science Foundation [81173139]; Major Research Plan of NSFC [21233003]; Asia-Pacific Cancer Research Foundation FX This study is supported by the National Key Technology R&D Program (2008BAI49B04), the China National Science Foundation (81173139), the Major Research Plan of NSFC (21233003) and Asia-Pacific Cancer Research Foundation. NR 69 TC 3 Z9 3 U1 0 U2 8 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5206 EI 1875-5992 J9 ANTI-CANCER AGENT ME JI Anti-Cancer Agents Med. Chem. PY 2014 VL 14 IS 10 BP 1343 EP 1350 PG 8 WC Oncology; Chemistry, Medicinal SC Oncology; Pharmacology & Pharmacy GA AT9CW UT WOS:000345226600005 PM 25173560 ER PT J AU Goto, T Koyama, Y Kondo, T Tsugawa, Y Hasegawa, K AF Goto, Tadahiro Koyama, Yasuaki Kondo, Takashiro Tsugawa, Yusuke Hasegawa, Kohei TI A comparison of the force applied on oral structures during intubation attempts between the Pentax-AWS airwayscope and the Macintosh laryngoscope: a high-fidelity simulator-based study SO BMJ OPEN LA English DT Article ID TRACHEAL INTUBATION; MANNEQUIN; DESIGN; SCOPE AB Objective: We sought to determine whether the use of Pentax-AWS Airwayscope (AWS) applied less force on oral structures during intubation attempts than a conventional direct laryngoscope (DL). Design: Prospective cross-over study. Participants: A total of 37 physicians (9 transitional-year residents, 20 emergency medicine residents and 8 emergency physicians) were enrolled. Interventions: We used four simulation scenarios according to the difficulty of intubation and devices and used a high-fidelity simulator to quantify the forces applied on the oral structures. Outcome measures: Primary outcomes were the maximum force applied on the maxillary incisors and tongue. Other outcomes of interest were time to intubation and glottic view during intubation attempts. Results: The maximum force applied on the maxillary incisors in the normal airway scenario was higher with the use of AWS than that with DL (107 newton (N) vs 77 N, p=0.02). By contrast, the force in the difficult airway scenario was significantly lower with the use of AWS than that of the DL (89 N vs 183 N, p<0.01). Likewise, the force applied on the tongue was significantly lower with the use of AWS than the use of DL in both airway scenarios (11 N vs 27 N, p<0.001 in the normal airway scenario; 12 N vs 40 N, p<0.01 in the difficult airway scenario). Conclusions: The use of AWS during intubation attempts was associated with decreased forces applied to oral structures in the simulated difficult airway scenario. C1 [Goto, Tadahiro] Univ Fukui Hosp, Dept Emergency Med, Fukui, Japan. [Koyama, Yasuaki] Univ Tsukuba Hosp, Dept Emergency & Crit Care Med, Ibaraki, Japan. [Kondo, Takashiro] Kyoto Univ, Grad Sch Med & Publ Hlth, Dept Healthcare Epidemiol, Kyoto, Japan. [Tsugawa, Yusuke] Harvard Univ, Harvard Interfac Initiat Hlth Policy, Cambridge, MA 02138 USA. [Hasegawa, Kohei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Goto, T (reprint author), Univ Fukui Hosp, Dept Emergency Med, Fukui, Japan. EM gto@u-fukui.ac.jp NR 21 TC 4 Z9 4 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2014 VL 4 IS 10 AR e006416 DI 10.1136/bmjopen-2014-006416 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AT2OP UT WOS:000344774500085 PM 25296656 ER PT J AU Doherty, K Archambault, E Kelly, B Rudolph, JL AF Doherty, Kelly Archambault, Elizabeth Kelly, Brittany Rudolph, James L. TI Delirium markers in older fallers: a case-control study SO CLINICAL INTERVENTIONS IN AGING LA English DT Article DE geriatrics; patient centered outcomes research; patient safety ID RANDOMIZED CONTROLLED-TRIAL; PATIENT SAFETY STRATEGY; PRONE PATIENT; HOSPITALIZED-PATIENTS; RESOURCE UTILIZATION; PREVENTION PROGRAMS; ELDERLY-PATIENTS; RISK; INPATIENTS; CONFUSION AB Background: When a hospitalized older patient falls or develops delirium, there are significant consequences for the patient and the health care system. Assessments of inattention and altered consciousness, markers for delirium, were analyzed to determine if they were also associated with falls. Methods: This retrospective case-control study from a regional tertiary Veterans Affairs referral center identified falls and delirium risk factors from quality databases from 2010 to 2012. Older fallers with complete delirium risk assessments prior to falling were identified. As a control, non-fallers were matched at a 3:1 ratio. Admission risk factors that were compared in fallers and non-fallers included altered consciousness, cognitive performance, attention, sensory deficits, and dehydration. Odds ratio (OR) was reported (95% confidence interval [CI]). Results: After identifying 67 fallers, the control population (n=201) was matched on age (74.4 +/- 9.8 years) and ward (83.6% medical; 16.4% intensive care unit). Inattention as assessed by the Months of the Year Backward test was more common in fallers (67.2% versus 50.8%, OR=2.0; 95% CI: 1.1-3.7). Fallers tended to have altered consciousness prior to falling (28.4% versus 12.4%, OR=2.8; 95% CI: 1.3-5.8). Conclusion: In this case-control study, alterations in consciousness and inattention, assessed prior to falling, were more common in patients who fell. Brief assessments of consciousness and attention should be considered for inclusion in fall prediction. C1 [Doherty, Kelly; Archambault, Elizabeth; Kelly, Brittany; Rudolph, James L.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Kelly, Brittany] Regis Coll, Sch Nursing Sci & Hlth Profess, Boston, MA USA. [Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Rudolph, James L.] Harvard Univ, Sch Med, Boston, MA USA. RP Rudolph, JL (reprint author), VA Boston Healthcare Syst GRECC, 150 S Huntington Ave Boston, Boston, MA 02130 USA. EM jrudolph@partners.org FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development; VA Delirium Patient Safety Center of Inquiry and T21 Alternative to Non-institutional Long Term Care award; VA Career Development Award FX We are indebted to the Veterans who participated in our fall- and delirium-prevention programs. We are thankful to the VABHS Boston Delirium Task Force and Patient Safety Officers for continued collaboration to improve outcomes for the Veterans we serve. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States Government. This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development. This study is supported by the VA Delirium Patient Safety Center of Inquiry and T21 Alternative to Non-institutional Long Term Care award. Doherty, Archambault, Kelly and Rudolph are employees of the US Government. Dr Rudolph also received support from a VA Career Development Award. The abstract for this paper was presented at the 4th annual meeting of the American Delirium Society in June 2014. NR 31 TC 2 Z9 2 U1 2 U2 5 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-1998 J9 CLIN INTERV AGING JI Clin. Interv. Aging PY 2014 VL 9 BP 2013 EP 2018 DI 10.2147/CIA.S71033 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AT9TO UT WOS:000345269200001 PM 25473272 ER PT S AU Wu, JW Runnels, JM Lin, CP AF Wu, Juwell W. Runnels, Judith M. Lin, Charles P. BE Bunting, KD Qu, CK TI Intravital Imaging of Hematopoietic Stem Cells in the Mouse Skull SO HEMATOPOIETIC STEM CELL PROTOCOLS, 3RD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Intravital imaging; Multi-photon imaging; Confocal imaging; Second harmonic generation signal; Bone marrow; Hematopoietic stem cell transplantation ID BONE-MARROW SINUSOIDS; PROGENITOR CELLS; FLUORESCENT PROTEINS; EMISSION-SPECTRA; IN-VITRO; NICHE; VIVO; TRACKING; MAINTENANCE; ENGRAFTMENT AB Over the past 50 years, much insight has been gained into the biology of hematopoietic stem cells (HSCs). Much of this information has been gained though isolation of specific bone marrow populations, and transplantation into irradiated recipients followed by characterization of chimeras months later. These studies have yielded insights into the function of HSCs, but have shed little light on the interactions of individual stem cells with their environment. Characterization of the behavior of single HSCs awaited the use of relatively noninvasive intravital microscopy, which allows one to identify rare cells in real time and follow them in multiple imaging sessions. Here we describe techniques used to image transplanted HSCs in the mouse calvarium using hybrid confocal/multi-photon microscopy and second harmonic imaging. For detection, fluorescently tagged HSCs are transplanted into a recipient mouse. The architecture of the bone marrow can be delineated using a combination of fluorescent probes and vascular dyes, second harmonic generation to detect the collagen signal from bone, and transgenic recipient mice containing specific fluorescent support cell populations. C1 [Wu, Juwell W.; Runnels, Judith M.; Lin, Charles P.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Wu, Juwell W.; Runnels, Judith M.; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Wu, Juwell W.; Runnels, Judith M.; Lin, Charles P.] Harvard Univ, Sch Med, Boston, MA USA. RP Wu, JW (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL100402, HL97794, HL097748] NR 47 TC 2 Z9 2 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1133-2; 978-1-4939-1132-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1185 BP 247 EP 265 DI 10.1007/978-1-4939-1133-2_17 D2 10.1007/978-1-4939-1133-2 PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BB6RC UT WOS:000344939500018 PM 25062634 ER PT S AU Ciuculescu, MF Brendel, C Harris, CE Williams, DA AF Ciuculescu, Marioara F. Brendel, Christian Harris, Chad E. Williams, David A. BE Bunting, KD Qu, CK TI Retroviral Transduction of Murine and Human Hematopoietic Progenitors and Stem Cells SO HEMATOPOIETIC STEM CELL PROTOCOLS, 3RD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE HSPC isolation; HSPC transduction; gamma-Retroviral vectors; Lentiviral vectors; Gene therapy ID WISKOTT-ALDRICH SYNDROME; LENTIVIRAL VECTORS; GENE-THERAPY; LEUKEMIA-VIRUS; IN-VIVO; EXPRESSION; INSULATORS; RECEPTORS; PROTEIN; MOUSE AB Genetic modification of cells using retroviral vectors is the method of choice when the cell population is difficult to transfect and/or requires persistent transgene expression in progeny cells. There are innumerable potential applications for these procedures in laboratory research and clinical therapeutic interventions. One paradigmatic example is the genetic modification of hematopoietic stem and progenitor cells (HSPCs). These are rare nucleated cells which reside in a specialized microenvironment within the bone marrow, and have the potential to self-renew and/or differentiate into all hematopoietic lineages. Due to their enormous regenerative capacity in steady state or under stress conditions these cells are routinely used in allogeneic bone marrow transplantation to reconstitute the hematopoietic system in patients with metabolic, inflammatory, malignant, and other hematologic disorders. For patients lacking a matched bone marrow donor, gene therapy of autologous hematopoietic stem cells has proven to be an alternative as highlighted recently by several successful gene therapy trials. Genetic modification of HSPCs using retrovirus vectors requires ex vivo manipulation to efficiently introduce the new genetic material into cells (transduction). Optimal culture conditions are essential to facilitate this process while preserving the stemness of the cells. The most frequently used retroviral vector systems for the genetic modifications of HSPCs are derived either from Moloney murine leukemia-virus (Mo-MLV) or the human immunodeficiency virus-1 (HIV-1) and are generally termed according to their genus gamma-retroviral (gamma-RV) or lentiviral vectors (LV), respectively. This chapter describes in a step-by-step fashion some techniques used to produce research grade vector supernatants and to obtain purified murine or human hematopoietic stem cells for transduction, as well as follow-up methods for analysis of transduced cell populations. C1 [Ciuculescu, Marioara F.; Brendel, Christian; Harris, Chad E.; Williams, David A.] Boston Childrens Hosp, Boston, MA 02115 USA. [Ciuculescu, Marioara F.; Brendel, Christian; Harris, Chad E.; Williams, David A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ciuculescu, MF (reprint author), Boston Childrens Hosp, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA113969]; NIDDK NIH HHS [R24 DK099808, R01 DK062757] NR 45 TC 4 Z9 4 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 978-1-4939-1133-2; 978-1-4939-1132-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1185 BP 287 EP 309 DI 10.1007/978-1-4939-1133-2_20 D2 10.1007/978-1-4939-1133-2 PG 23 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BB6RC UT WOS:000344939500021 PM 25062637 ER PT J AU Shechter, A St-Onge, MP Kuna, ST Zammit, G RoyChoudhury, A Newman, AB Millman, RP Reboussin, DM Wadden, TA Jakicic, JM Pi-Sunyer, FX Wing, RR Foster, GD AF Shechter, Ari St-Onge, Marie-Pierre Kuna, Samuel T. Zammit, Gary RoyChoudhury, Arindam Newman, Anne B. Millman, Richard P. Reboussin, David M. Wadden, Thomas A. Jakicic, John M. Pi-Sunyer, F. Xavier Wing, Rena R. Foster, Gary D. CA Look Ahead Res Grp TI Sleep Architecture Following a Weight Loss Intervention in Overweight and Obese Patients with Obstructive Sleep Apnea and Type 2 Diabetes: Relationship to Apnea-Hypopnea Index SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE sleep architecture; obstructive sleep apnea; obesity; type 2 diabetes ID RANDOMIZED CONTROLLED-TRIAL; LIFE-STYLE INTERVENTION; SLOW-WAVE SLEEP; CARDIOVASCULAR RISK-FACTORS; AIRWAY PRESSURE THERAPY; EYE-MOVEMENT SLEEP; LOW ENERGY DIET; DAYTIME SLEEPINESS; BARIATRIC SURGERY; DURATION AB Study Objectives: To determine if weight loss and/or changes in apnea-hypopnea index (AHI) improve sleep architecture in overweight/obese adults with type 2 diabetes (T2D) and obstructive sleep apnea (OSA). Methods: This was a randomized controlled trial including 264 overweight/obese adults with T2D and OSA. Participants were randomized to an intensive lifestyle intervention (ILI) or a diabetes and support education (DSE) control group. Measures included anthropometry, AHI, and sleep at baseline and year-1, year-2, and year-4 follow-ups. Results: Changes in sleep duration (total sleep time [TST]), continuity [wake after sleep onset (WASO)], and architecture stage 1, stage 2, slow wave sleep, and REM sleep) from baseline to year 1, 2, and 4 did not differ between ILI and DSE. Repeated-measure mixed-model analyses including data from baseline through year-4 for all participants demonstrated a significant positive association between AHI and stage 1 sleep (p < 0.001), and a significant negative association between AHI and stage 2 (p = 0.01) and REM sleep (p < 0.001), whereas changes in body weight had no relation to any sleep stages or TST. WASO had a significant positive association with change in body weight (p = 0.009). Conclusions: Compared to control, the ILI did not induce significant changes in sleep across the 4-year follow-up. In participants overall, reduced AHI in overweight/obese adults with T2D and OSA was associated with decreased stage 1, and increased stage 2 and REM sleep. These sleep architecture changes are more strongly related to reductions in AHI than body weight, whereas WASO may be more influenced by weight than AHI. C1 [Shechter, Ari; St-Onge, Marie-Pierre; RoyChoudhury, Arindam; Pi-Sunyer, F. Xavier] Columbia Univ, New York, NY 10032 USA. [Kuna, Samuel T.; Wadden, Thomas A.] Univ Penn, Philadelphia, PA 19104 USA. [Kuna, Samuel T.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Zammit, Gary] Clinilabs, New York, NY USA. [Newman, Anne B.; Jakicic, John M.] Univ Pittsburgh, Pittsburgh, PA USA. [Millman, Richard P.; Wing, Rena R.] Brown Univ, Providence, RI 02912 USA. [Reboussin, David M.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Foster, Gary D.] Temple Univ, Philadelphia, PA 19122 USA. RP Shechter, A (reprint author), Columbia Univ, New York Obes Res Ctr, 622 West 168th St, New York, NY 10032 USA. EM as4180@columbia.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU National Institutes of Health NHLBI grant [HL070301]; NIDDK [DK60426, DK56992, DK057135, DK007559]; Philips Respironics; Abbott; Actelion; Ancile; Apnex; Arena; Aventis; Cephalon Inc; CHDI; Elan; Epis; Evotec; Forest; Galderma; Glaxo Smith Kline; H. Lundbeck A/S; King; Merck and Co.; National Institute of Health (NIH); Neurim; Neurocrine Biosciences; Neurogen; Organon; Orphan Medical; Otsuka; Pfizer; Predix; Respironics; Sanofi-Aventis; Sanofi-Synthelabo; Schering-Plough; Sepracor; Shire; Samaxon; Takeda Pharmaceuticals North America; Targacept; Thymon; Transcept; UCB Pharma; Vanda; Wyeth-Ayerst Research; King Pharmaceuticals; McNeil; Vela Pharmaceuticals; Novo Nordisk; NutriSystem; BodyMedia, Inc.; JennyCraig; Coca Cola Company; Orexigen FX This was not an industry supported study. The study was supported by the National Institutes of Health NHLBI grant HL070301 and NIDDK grants DK60426, DK56992, DK057135, and DK007559. Dr. Kuna has received research support from Philips Respironics. Dr. Zammit is a consultant for Actelion, Alexza, Arena, Aventis, Biovail, Boehringer-Ingelheim, Cephalon, Elan, Eli Lilly, Evotec, Forest, Glaxo Smith Kline, Jazz, King Pharmaceuticals, Ligand, McNeil, Merck, Neurocrine Biosciences, Organon, Phizer, Renovis, Sanofi-Aventis, Select Comfort, Sepracor, Shire, Somnus, Takeda Pharmaceuticals, Vela, Wyeth-Ayerst Research; provides expert testimony for Acorda; has grants or grants pending from Abbott, Actelion, Ancile, Apnex, Arena, Aventis, Cephalon Inc, CHDI, Elan, Epis, Evotec, Forest, Galderma, Glaxo Smith Kline, H. Lundbeck A/S, King, Merck and Co., National Institute of Health (NIH), Neurim, Neurocrine Biosciences, Neurogen, Organon, Orphan Medical, Otsuka, Pfizer, Predix, Respironics, Sanofi-Aventis, Sanofi-Synthelabo, Schering-Plough, Sepracor, Shire, Samaxon, Takeda Pharmaceuticals North America, Targacept, Thymon, Transcept, UCB Pharma, Predix, Vanda, Wyeth-Ayerst Research. And has received payment for lectures from Neurocrine Biosciences, King Pharmaceuticals, McNeil, Sanofi-Aventis, Sanofi-Synthelabo, Sepracor, Takeda Pharmaceuticals, Vela Pharmaceuticals, Wyeth-Ayerst Research. Dr. Wadden serves on advisory boards for Orexigen Therapeutics and Novo Nordisk and has received grant support from Novo Nordisk and NutriSystem. Dr. Jakicic is a member of Free & Clear Scientific Advisory Board, has received grants or has grants pending from BodyMedia, Inc., and receives payment for lectures by JennyCraig. Dr. Foster serves on the Scientific Advisory Board of Con Agra Foods, Nutrisystem, Amylin, GI Dynamics, and United Health Group. He has received grants from Coca Cola Company and Orexigen. The other authors have indicated no financial conflicts of interest. NR 42 TC 2 Z9 2 U1 0 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 EI 1550-9397 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2014 VL 10 IS 11 BP 1205 EP 1211 DI 10.5664/jcsm.4202 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AT8XT UT WOS:000345213100007 PM 25325608 ER PT B AU Oosterwijk, S Barrett, LF AF Oosterwijk, Suzanne Barrett, Lisa Feldman BE Shapiro, L TI EMBODIMENT IN THE CONSTRUCTION OF EMOTION EXPERIENCE AND EMOTION UNDERSTANDING SO ROUTLEDGE HANDBOOK OF EMBODIED COGNITION SE Routledge Handbooks in Philosophy LA English DT Article; Book Chapter ID BRAINS DEFAULT NETWORK; ANTERIOR INSULA; FUNCTIONAL CONNECTIVITY; FACIAL EXPRESSIONS; SOCIAL COGNITION; NEURAL-NETWORKS; SYSTEMS; EMPATHY; SELF; MIND C1 [Oosterwijk, Suzanne] Univ Amsterdam, Dept Social Psychol, NL-1012 WX Amsterdam, Netherlands. [Barrett, Lisa Feldman] Northeastern Univ, Boston, MA USA. [Barrett, Lisa Feldman] Northeastern Univ, Interdisciplinary Affect Sci Lab IASLab, Boston, MA USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Barrett, Lisa Feldman] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Oosterwijk, S (reprint author), Univ Amsterdam, Dept Social Psychol, NL-1012 WX Amsterdam, Netherlands. NR 70 TC 3 Z9 3 U1 1 U2 2 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-315-77584-5; 978-0-415-62361-2 J9 ROUTLEDGE HBK PHILOS PY 2014 BP 250 EP 260 PG 11 WC Philosophy; Psychology, Experimental SC Philosophy; Psychology GA BB3RA UT WOS:000342997900025 ER PT J AU Turker, NS Heidari, P Kucherlapati, R Kucherlapati, M Mahmood, U AF Turker, N. Selcan Heidari, Pedram Kucherlapati, Raju Kucherlapati, Melanie Mahmood, Umar TI An EGFR Targeted PET Imaging Probe for the Detection of Colonic Adenocarcinomas in the Setting of Colitis SO THERANOSTICS LA English DT Article DE Positron emission tomography (PET) imaging; molecular imaging; EGFR; ulcerative colitis; colorectal cancer; mouse models ID INFLAMMATORY-BOWEL-DISEASE; GROWTH-FACTOR RECEPTOR; BREAST-CANCER XENOGRAFTS; HERCEPTIN FAB FRAGMENTS; COLORECTAL-CANCER; ULCERATIVE-COLITIS; INTESTINAL CANCER; EXPRESSION; MICE; ANTIBODY AB Colorectal cancer is a serious complication associated with inflammatory bowel disease, often indistinguishable by screening with conventional FDG PET probes. We have developed an alternative EGFR-targeted PET imaging probe that may be used to overcome this difficulty, and successfully assessed its utility for neoplastic lesion detection in preclinical models. Cetuximab F(ab')2 fragments were enzymatically generated, purified, and DOTA-conjugated. Radiolabeling was performed with Ga-67 for cell based studies and Cu-64 for in vivo imaging. Competitive binding studies were performed on CT26 cells to assess affinity (K-D) and receptors per cell (B-max). In vivo imaging using the EGFR targeted PET probe and F-18 FDG was performed on CT26 tumor bearing mice in both control and dextran sodium sulfate (DSS) induced colitis settings. Spontaneous adenomas in genetically engineered mouse (GEM) models of colon cancer were additionally imaged. The EGFR imaging agent was generated with high purity (> 98%), with a labeling efficiency of 60 +/- 5% and >= 99% radiochemical purity. The K-D was 6.6 +/- 0.7 nM and the B-max for CT26 cells was 3.3 +/- 0.1 x 10(6) receptors/cell. Target to background ratios (TBR) for CT26 tumors compared to colonic uptake demonstrated high values for both F-18-FDG (3.95 +/- 0.13) and the developed Cu-64-DOTA-cetuximab-F(ab')2 probe (4.42 +/- 0.11) in control mice. The TBR for the EGFR targeted probe remained high (3.78 +/- 0.06) in the setting of colitis, while for F-18 FDG, this was markedly reduced (1.54 +/- 0.08). Assessment of the EGFR targeted probe in the GEM models demonstrated a correlation between radiotracer uptake in spontaneous colonic lesions and the EGFR staining level ex vivo. A clinically translatable PET imaging probe was successfully developed to assess EGFR. The imaging agent can detect colonic tumors with a high TBR for detection of in situ lesions in the setting of colitis, and opens the possibility for a new approach for screening high-risk patients. C1 [Turker, N. Selcan; Heidari, Pedram; Mahmood, Umar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Boston, MA USA. [Kucherlapati, Raju; Kucherlapati, Melanie] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Genet, Boston, MA USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA 02114 USA. EM umahmood@mgh.harvard.edu FU Dubai Harvard Foundation for Medical Research (DHFMR) [223439]; [U01CA084301]; [P50CA127003]; [U01CA143056] FX This study was supported by U01CA084301, P50CA127003, and U01CA143056. N. Selcan Turker supported by the Dubai Harvard Foundation for Medical Research (DHFMR, grant number: 223439). NR 47 TC 7 Z9 7 U1 2 U2 22 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2014 VL 4 IS 9 BP 893 EP 903 DI 10.7150/thno.9425 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AT8YH UT WOS:000345214400003 PM 25057314 ER PT J AU Yoon, YI Kwon, YS Cho, HS Heo, SH Park, KS Park, SG Lee, SH Hwang, SI Kim, YI Jae, HJ Ahn, GJ Cho, YS Lee, H Lee, HJ Yoon, TJ AF Yoon, Young Il Kwon, Yong-Su Cho, Hee-Sang Heo, Sun-Hee Park, Kyeong Soon Park, Sang Gyu Lee, Soo-Hong Hwang, Seung Il Kim, Young Il Jae, Hwan Jun Ahn, Gook-Jun Cho, Young-Seok Lee, Hakho Lee, Hak Jong Yoon, Tae-Jong TI Ultrasound-Mediated Gene and Drug Delivery Using a Microbubble-Liposome Particle System SO THERANOSTICS LA English DT Article DE Microbubble; Liposome; Ultrasound imaging; Drug and gene delivery; Theranostics ID BREAST-CANCER-CELLS; CONTRAST AGENTS; THERANOSTIC NANOPARTICLES; THERAPY; NANOMEDICINE; CHALLENGES; RETENTION; COMPLEXES; APOPTOSIS; IMPACT AB Theranostic agents present a promising clinical approach for cancer detection and treatment. We herein introduce a microbubble and liposome complex (MB-Lipo) developed for ultrasound (US) imaging and activation. The MB-Lipo particles have a hybrid structure consisting of a MB complexed with multiple Lipos. The MB components are used to generate high echo signals in US imaging, while the Lipos serve as a versatile carrier of therapeutic materials. MB-Lipo allows high contrast US imaging of tumor sites. More importantly, the application of high acoustic pressure bursts MBs, which releases therapeutic Lipos and further enhances their intracellular delivery through sonoporation effect. Both imaging and drug release could thus be achieved by a single US modality, enabling in situ treatment guided by real-time imaging. The MB-Lipo system was applied to specifically deliver anti-cancer drug and genes to tumor cells, which showed enhanced therapeutic effect. We also demonstrate the clinical potential of MB-Lipo by imaging and treating tumor in vivo. C1 [Yoon, Young Il; Hwang, Seung Il; Kim, Young Il; Jae, Hwan Jun; Lee, Hak Jong] Seoul Natl Univ, Coll Med, Dept Radiol, Seoul 110799, South Korea. [Yoon, Young Il; Hwang, Seung Il; Lee, Hak Jong] Seoul Natl Univ, Bundang Hosp, Dept Radiol, Seungnam 463707, South Korea. [Yoon, Young Il; Lee, Hak Jong] Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Dept Transdisciplinary Studies, Program Nano Sci & Technol, Suwon 443270, South Korea. [Kwon, Yong-Su; Cho, Hee-Sang; Yoon, Tae-Jong] CHA Univ, Coll Life Sci, Dept Appl Biosci, Pochon 135081, South Korea. [Heo, Sun-Hee; Park, Kyeong Soon; Park, Sang Gyu; Lee, Soo-Hong] CHA Univ, Coll Life Sci, Dept Biomed Sci, Pochon 135081, South Korea. Seoul Natl Univ Hosp, Coll Med, Dept Radiol, Seoul 110744, South Korea. [Ahn, Gook-Jun] KBIO Osong Med Innovat Fdn, Lab Anim Ctr, Cheongwon 363951, Chungbuk, South Korea. [Cho, Young-Seok] Catholic Univ Korea, Coll Med, Uijeongbu St Marys Hosp, Dept Gastroenterol, Uijongbu 480717, South Korea. [Lee, Hakho] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Lee, Hak Jong] Seoul Natl Univ, Adv Inst Convergence Technol, Inst Nanoconvergence, Nanoimaging & Therapy Res Ctr, Seoul 151, South Korea. RP Lee, H (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM hlee@mgh.harvard.edu; hakjlee@snu.ac.kr; tjyoon@cha.ac.kr FU National Research Foundation of Korea [2010-0008846, 2010-0009271]; O-song Medical Innovation Foundation R&D project of Ministry of Health and Welfare in South Korea [HO13C0009]; National Institute of Health [R01-HL113156]; Seoul National University Hospital [04-2012-0670] FX We thank Dr. Shao (MGH) for critically reviewing the manuscript. This work was funded through the National Research Foundation of Korea (the Basic Science Research Program 2010-0008846 to T.-J. Yoon and 2010-0009271 to H. J. Lee) and partially supported by a grant of O-song Medical Innovation Foundation R&D project (HO13C0009) of Ministry of Health and Welfare in South Korea. H. Lee acknowledges a support by the National Institute of Health Grants, R01-HL113156. H. J. Jae also acknowledges a support by Seoul National University Hospital research fund (04-2012-0670). NR 41 TC 20 Z9 23 U1 8 U2 30 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2014 VL 4 IS 11 BP 1133 EP 1144 DI 10.7150/thno.9945 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AT8XR UT WOS:000345212900007 PM 25250094 ER PT J AU Li, X Yang, CY Wu, K Hu, YZ Han, YF Liang, SH AF Li, Xin Yang, Chengyu Wu, Kai Hu, Yongzhou Han, Yifeng Liang, Steven H. TI A Highly Specific Probe for Sensing Hydrogen Sulfide in Live Cells Based on Copper-Initiated Fluorogen with Aggregation-Induced Emission Characteristics SO THERANOSTICS LA English DT Article DE hydrogen sulfide; fluorescent probe; cell imaging; aggregation-induced emission ID LIVING CELLS; FLUORESCENT-PROBES; MOLECULE; INSIGHTS; BIOLOGY; RAT; H2S AB Here we reported the first fluorescent probe with aggregation-induced emission characteristics, namely AIE-S, for the detection of hydrogen sulfide (H2S) in live cells. The detection system is selective for complicated biological application and the response is fast enough to complete within seconds. Moreover, the probe exhibits the unique advantage of being immune to aggregation-caused quenching which is a detrimental phenomenon limiting the application of most current available H2S fluorescent probes. The detection mechanism was investigated and postulated to be S-2-initiated de-coordination and thereafter aggregation of the AIE-S complex. C1 [Li, Xin; Hu, Yongzhou] Zhejiang Univ, Coll Pharmaceut Sci, ZJU ENS Joint Lab Med Chem, Hangzhou 310058, Zhejiang, Peoples R China. [Yang, Chengyu; Wu, Kai; Han, Yifeng] Zhejiang Sci Tech Univ, Dept Chem, Key Lab Adv Text Mat & Mfg Technol, Hangzhou 310028, Zhejiang, Peoples R China. [Liang, Steven H.] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Liang, Steven H.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Han, YF (reprint author), Zhejiang Sci Tech Univ, Dept Chem, Key Lab Adv Text Mat & Mfg Technol, Hangzhou 310028, Zhejiang, Peoples R China. EM hanyf@zstu.edu.cn; Liang.Steven@mgh.harvard.edu NR 34 TC 11 Z9 11 U1 7 U2 46 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2014 VL 4 IS 12 BP 1233 EP 1238 DI 10.7150/thno.10330 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AT8WI UT WOS:000345209500007 PM 25285171 ER PT J AU Emani, S Ting, DY Healey, M Lipsitz, SR Karson, AS Einbinder, JS Leinen, L Suric, V Bates, DW AF Emani, S. Ting, D. Y. Healey, M. Lipsitz, S. R. Karson, A. S. Einbinder, J. S. Leinen, L. Suric, V. Bates, D. W. TI Physician beliefs about the impact of meaningful use of the EHR A Cross-Sectional Study SO APPLIED CLINICAL INFORMATICS LA English DT Article DE Electronic health records; physicians; beliefs; meaningful use; evaluation ID ELECTRONIC HEALTH RECORDS; USE CRITERIA; ADOPTION; SYSTEMS; CARE; GUIDELINES AB Background: As adoption and use of electronic health records (EHRs) grows in the United States, there is a growing need in the field of applied clinical informatics to evaluate physician perceptions and beliefs about the impact of EHRs. The meaningful use of EHR incentive program provides a suitable context to examine physician beliefs about the impact of EHRs. Objective: Contribute to the sparse literature on physician beliefs about the impact of EHRs in areas such as quality of care, effectiveness of care, and delivery of care. Methods: A cross-sectional online survey of physicians at two academic medical centers (AMCs) in the northeast who were preparing to qualify for the meaningful use of EHR incentive program. Results: Of the 1,797 physicians at both AMCs who were preparing to qualify for the incentive program, 967 completed the survey for an overall response rate of 54%. Only 23% and 27% of physicians agreed or strongly agreed that meaningful use of the EHR will help them improve the care they personally deliver and improve quality of care respectively. Physician specialty was significantly associated with beliefs; e. g., 35% of primary care physicians agreed or strongly agreed that meaningful use will improve quality of care compared to 26% of medical specialists and 21% of surgical specialists (p=0.009). Satisfaction with outpatient EHR was also significantly related to all belief items. Conclusions: Only about a quarter of physicians in our study responded positively that meaningful use of the EHR will improve quality of care and the care they personally provide. These findings are similar to and extend findings from qualitative studies about negative perceptions that physicians hold about the impact of EHRs. Factors outside of the regulatory context, such as physician beliefs, need to be considered in the implementation of the meaningful use of the EHR incentive program. C1 [Emani, S.; Healey, M.; Lipsitz, S. R.; Einbinder, J. S.; Suric, V.; Bates, D. W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gen Internal Med,Dept Med, Boston, MA 02115 USA. [Ting, D. Y.] Massachusetts Gen Hosp, Massachusetts Gen Phys Org, Boston, MA 02114 USA. [Healey, M.] Brigham & Womens Hosp, Brigham & Womens Phys Org, Boston, MA 02120 USA. [Karson, A. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Decis Support Unit, Boston, MA USA. [Leinen, L.] Partners HealthCare, Informat Serv, Boston, MA USA. [Bates, D. W.] Harvard Univ, Sch Publ Hlth, Dept Healthcare Policy & Management, Boston, MA 02115 USA. RP Emani, S (reprint author), Brigham & Womens Hosp, Div Gen Internal Med, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM semani1@partners.org FU Partners-Siemens Informatics Research Council (PSRC) FX Funding for this study was provided by the Partners-Siemens Informatics Research Council (PSRC). NR 26 TC 3 Z9 3 U1 1 U2 5 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 3 BP 789 EP 801 DI 10.4338/ACI-2014-05-RA-0050 PG 13 WC Medical Informatics SC Medical Informatics GA AT0AU UT WOS:000344600100004 PM 25298817 ER PT J AU Bruinsma, BG Sridharan, GV Weeder, PD Avruch, JH Yeh, H Markmann, JF Yarmush, ML Uygun, K AF Bruinsma, Bote G. Sridharan, Gautham V. Weeder, Pepijn D. Avruch, James H. Yeh, Heidi Markmann, James F. Yarmush, Martin L. Uygun, Korkut TI Dynamic Characterization of Human Livers during ex vivo Machine Perfusion 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 [Bruinsma, Bote G.; Sridharan, Gautham V.; Weeder, Pepijn D.; Yarmush, Martin L.; Uygun, Korkut] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [Avruch, James H.; Yeh, Heidi; Markmann, James F.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 7 BP 200A EP 200A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483800008 ER PT J AU Chen, HH Wei, L Rotile, NJ Farrar, CT Tanabe, KK Fuchs, BC Caravan, P AF Chen, Howard H. Wei, Lan Rotile, Nicholas J. Farrar, Christian T. Tanabe, Kenneth K. Fuchs, Bryan C. Caravan, Peter TI Quantitative molecular magnetic resonance imaging (MRI) of lysyl oxidase-mediated collagen crosslinking during liver fibrosis 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 [Chen, Howard H.; Rotile, Nicholas J.; Farrar, Christian T.; Caravan, Peter] Harvard Univ, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. [Wei, Lan; Tanabe, Kenneth K.; Fuchs, Bryan C.] Massachusetts Gen Hosp, Ctr Canc, Div Surg Oncol, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 17 BP 205A EP 205A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483800018 ER PT J AU Fuchs, BC Farrar, CT DePeralta, DK Day, H Keil, B Lauwers, GY Wei, L Subramaniam, A Tanabe, KK Caravan, P AF Fuchs, Bryan C. Farrar, Christian T. DePeralta, Danielle K. Day, Helen Keil, Boris Lauwers, Gregory Y. Wei, Lan Subramaniam, Arun Tanabe, Kenneth K. Caravan, Peter TI Molecular MR imaging of Collagen Accurately Monitors Reduced Biliary Fibrosis Progression in Response to Rapamycin 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 [Fuchs, Bryan C.; Farrar, Christian T.; DePeralta, Danielle K.; Day, Helen; Keil, Boris; Lauwers, Gregory Y.; Wei, Lan; Tanabe, Kenneth K.; Caravan, Peter] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Subramaniam, Arun] Sanofi, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 18 BP 205A EP 206A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483800019 ER PT J AU Corey, K Vuppalanchi, R Wilson, L Cummings, O Chalasani, NP AF Corey, Kathleen Vuppalanchi, Raj Wilson, Laura Cummings, Oscar Chalasani, Naga P. TI NASH Resolution is Associated with Improvements in HDL and Triglycerides But Not in LDL or Non-HDL-C 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 [Corey, Kathleen] Massachusetts Gen Hosp, GI, Boston, MA 02114 USA. [Vuppalanchi, Raj; Cummings, Oscar; Chalasani, Naga P.] Indiana Univ, Indianapolis, IN 46204 USA. [Wilson, Laura] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 56 BP 224A EP 225A PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483800057 ER PT J AU Chidi, AP Rogal, SS Bryce, CL Fine, MJ Good, CB Myaskovsky, L Rustgi, VK Tsung, A Smith, KJ AF Chidi, Alexis P. Rogal, Shari S. Bryce, Cindy L. Fine, Michael J. Good, Chester B. Myaskovsky, Larissa Rustgi, Vinod K. Tsung, Allan Smith, Kenneth J. TI Cost-Effectiveness of Novel Hepatitis C Drug Regimens Among Treatment-Experienced US Veterans 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 [Chidi, Alexis P.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Chidi, Alexis P.; Fine, Michael J.; Good, Chester B.; Myaskovsky, Larissa] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Rogal, Shari S.; Rustgi, Vinod K.] Univ Pittsburgh, Div GI Hepatol & Nutr, Pittsburgh, PA USA. [Bryce, Cindy L.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Bryce, Cindy L.; Fine, Michael J.; Myaskovsky, Larissa; Smith, Kenneth J.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Good, Chester B.] Dept Vet Affairs, Pittsburgh, PA USA. [Rustgi, Vinod K.; Tsung, Allan] Univ Pittsburgh, Starzl Transplant Inst, Pittsburgh, PA USA. [Tsung, Allan] Univ Pittsburgh, Div Hepatobiliary & Pancreat Surg, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 75 BP 234A EP 234A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483801009 ER PT J AU Tran, TT Morgan, TR Thuluvath, PJ Etzkorn, K Hinestrosa, F Tong, M McNally, J Brainard, DM Han, LL Doehle, B Mogalian, E McHutchison, JG Chung, RT Everson, GT AF Tran, Tram T. Morgan, Timothy R. Thuluvath, Paul J. Etzkorn, Kyle Hinestrosa, Federico Tong, Myron McNally, John Brainard, Diana M. Han, Lingling Doehle, Brian Mogalian, Erik McHutchison, John G. Chung, Raymond T. Everson, Gregory T. TI Safety and Efficacy of Treatment with Sofosbuvir+GS-5816 +/- Ribavirin for 8 or 12 Weeks in Treatment Naive Patients with Genotype 1-6 HCV Infection 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 [Tran, Tram T.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Morgan, Timothy R.] VA Long Beach, Long Beach, CA USA. [Thuluvath, Paul J.] Mercy Med Ctr, Baltimore, MD USA. [Etzkorn, Kyle] Borland Groover Clin, Jacksonville, FL USA. [Hinestrosa, Federico] Orlando Immunol Ctr, Orlando, FL USA. [Tong, Myron] Huntington Med Res Inst, Pasadena, CA USA. [McNally, John; Brainard, Diana M.; Han, Lingling; Doehle, Brian; Mogalian, Erik; McHutchison, John G.] Gilead Sci Inc, Foster City, CA 94404 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Everson, Gregory T.] Univ Denver Colorado, Aurora, CO USA. NR 0 TC 5 Z9 5 U1 0 U2 0 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 80 BP 237A EP 237A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483801014 ER PT J AU Saxena, V Flemming, JA Shen, H Terrault, N Monto, A Rongey, C AF Saxena, Varun Flemming, Jennifer A. Shen, Hui Terrault, Norah Monto, Alexander Rongey, Catherine TI Facility and patient level predictors of endoscopic variceal screening within the largest integrated healthcare system in the United States 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 [Saxena, Varun; Shen, Hui; Terrault, Norah; Monto, Alexander; Rongey, Catherine] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Shen, Hui; Monto, Alexander; Rongey, Catherine] San Francisco VA Med Ctr, San Francisco, CA USA. [Flemming, Jennifer A.] Queens Univ, Kingston, ON K7L 3N6, Canada. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 95 BP 246A EP 246A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483801029 ER PT J AU Rahman, K Thorn, N Kumar, P Nusrat, A Parkos, CA Anania, FA AF Rahman, Khalidur Thorn, Natalie Kumar, Pradeep Nusrat, Asma Parkos, Charles A. Anania, Frank A. TI Compromised intestinal epithelial barrier function is a major contributor in the progression of diet induced non-alcoholic fatty liver disease (NAFLD) to steatohepatitis (NASH) and is driven primarily by innate immune activation 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 [Rahman, Khalidur; Thorn, Natalie; Kumar, Pradeep; Anania, Frank A.] Emory Univ, Sch Med, Dept Med, Div Digest Dis, Atlanta, GA USA. [Rahman, Khalidur; Anania, Frank A.] Atlanta VA Med Ctr, US Dept Vet Affairs, Decatur, GA USA. [Nusrat, Asma; Parkos, Charles A.] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 97 BP 247A EP 247A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483801031 ER PT J AU King, LY Khalili, H Huang, ES Chung, RT Chan, AT AF King, Lindsay Y. Khalili, Hamed Huang, Edward S. Chung, Raymond T. Chan, Andrew T. TI Diabetes mellitus is associated with an increased risk of HCC in a large prospective cohort with long term follow-up 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 [King, Lindsay Y.; Khalili, Hamed; Chung, Raymond T.; Chan, Andrew T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Huang, Edward S.] Palo Alto Med Fdn, Mountain View, CA 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 165 BP 281A EP 281A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483801099 ER PT J AU Long, MT Wang, N Larson, MG Mitchell, GF Palmisano, JN Ramachandran, VS Hoffmann, U Speliotes, EK Vita, JA Benjamin, EJ Fox, CS Hamburg, N AF Long, Michelle T. Wang, Na Larson, Martin G. Mitchell, Gary F. Palmisano, Joseph N. Ramachandran, Vasan S. Hoffmann, Udo Speliotes, Elizabeth K. Vita, Joseph A. Benjamin, Emelia J. Fox, Caroline S. Hamburg, Naomi TI The association of vascular function and non-alcoholic fatty liver disease: the Framingham Heart Study 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 [Long, Michelle T.] Boston Med Ctr, Boston, MA USA. [Long, Michelle T.; Larson, Martin G.; Ramachandran, Vasan S.; Benjamin, Emelia J.; Fox, Caroline S.; Hamburg, Naomi] NHLBI, Framingham Heart Study, Framingham, MA USA. [Vita, Joseph A.; Benjamin, Emelia J.; Hamburg, Naomi] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Vita, Joseph A.; Benjamin, Emelia J.; Hamburg, Naomi] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Hypertens & Metab, Boston, MA 02115 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wang, Na; Larson, Martin G.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Mitchell, Gary F.] Cardiovasc Engn Inc, Waltham, MA USA. [Palmisano, Joseph N.] Boston Univ, Sch Publ Hlth, Data Corrdinating Ctr, Boston, MA USA. [Ramachandran, Vasan S.] Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA. [Speliotes, Elizabeth K.] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 214 BP 306A EP 306A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483801148 ER PT J AU Berry, K Taylor, J Liou, IW Ioannou, GN AF Berry, Kristin Taylor, Justin Liou, Iris W. Ioannou, George N. TI Portal vein thrombosis is not associated with increased mortality in cirrhotic patients 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 [Berry, Kristin; Liou, Iris W.; Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Taylor, Justin; Ioannou, George N.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 386 BP 391A EP 392A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483801318 ER PT J AU Karimian, N op den Dries, S Weeder, PD Westerkamp, A Bomfati, F Wiersema-Buist, J Bruinsma, BG Gouw, AS Markmann, JF Lisman, T Yeh, H Uygun, K Martins, PN Porte, RJ AF Karimian, Negin op den Dries, Sanna Weeder, Pepijn D. Westerkamp, Andrie Bomfati, Fernanda Wiersema-Buist, Janneke Bruinsma, Bote G. Gouw, Annette S. Markmann, James F. Lisman, Ton Yeh, Heidi Uygun, Korkut Martins, Paulo N. Porte, Robert J. TI Injury of Peribiliary Glands of Donor Liver Bile Ducts Plays a Pivotal Role in the Development of Non-anastomotic Biliary Strictures after Liver Transplantation 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 [Karimian, Negin; op den Dries, Sanna; Weeder, Pepijn D.; Westerkamp, Andrie; Bomfati, Fernanda; Wiersema-Buist, Janneke; Lisman, Ton; Porte, Robert J.] Univ Med Ctr Groningen, Dept Surg, Sect Hepatobiliary Surg & Liver Transplantat, NL-9713 AV Groningen, Netherlands. [op den Dries, Sanna; Weeder, Pepijn D.; Markmann, James F.; Yeh, Heidi; Martins, Paulo N.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Gouw, Annette S.] Univ Med Ctr Groningen, Dept Pathol, NL-9713 AV Groningen, Netherlands. [Bruinsma, Bote G.; Uygun, Korkut] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med Surg Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 506 BP 447A EP 448A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483802004 ER PT J AU Basu, P Shah, NJ Lee, D Aloysius, M Gress, FG AF Basu, Patrick Shah, Niraj J. Lee, David Aloysius, M. Gress, Frank G. TI Novel colonoscopy preparation of organic coconut water with Miralax and Dulcolax in split doses for decompensated cirrhotics. A randomized double blinded open labelled clinical pilot single centered observational study. COSMIC Study 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 [Basu, Patrick; Gress, Frank G.] Columbia Univ, Sch Phys & Surg, New York, NY USA. [Basu, Patrick; Lee, David; Aloysius, M.] Kings Cty Hosp Med Ctr, New York, NY USA. [Shah, Niraj J.] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, New York, NY 10029 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 652 BP 516A EP 516A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483802148 ER PT J AU Mueller, JL King, LY Johnson, KB Gao, T Nephew, LD Kothari, D Simpson, MA Wei, L Corey, KE Misdraji, J Lee, JH Fuchs, BC Tanabe, KK Gordon, FD Curry, MP Chung, RT AF Mueller, Jessica L. King, Lindsay Y. Johnson, Kara B. Gao, Tian Nephew, Lauren D. Kothari, Darshan Simpson, Mary Ann Wei, Lan Corey, Kathleen E. Misdraji, Joseph Lee, Joon Hyoek Fuchs, Bryan C. Tanabe, Kenneth K. Gordon, Frederic D. Curry, Michael P. Chung, Raymond T. TI Impact of EGF, IL28B, and PNPLA3 polymorphisms on the outcome of allograft hepatitis C: a multicenter study 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 [Mueller, Jessica L.; King, Lindsay Y.; Johnson, Kara B.; Corey, Kathleen E.; Chung, Raymond T.] Massachusetts Gen Hosp, Div Gastroenterol, Dept Med, Boston, MA 02114 USA. [King, Lindsay Y.; Johnson, Kara B.; Kothari, Darshan; Corey, Kathleen E.; Fuchs, Bryan C.; Tanabe, Kenneth K.; Gordon, Frederic D.; Curry, Michael P.; Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. [Kothari, Darshan; Curry, Michael P.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gastroenterol, Boston, MA 02215 USA. [Simpson, Mary Ann; Gordon, Frederic D.] Lahey Hosp & Med Ctr, Div Gastroenterol, Dept Med, Burlington, MA USA. [Wei, Lan; Fuchs, Bryan C.; Tanabe, Kenneth K.] Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. [Misdraji, Joseph] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Gao, Tian] Boston Med Ctr, Div Gastroenterol, Dept Med, Boston, MA USA. [Nephew, Lauren D.] Univ Penn Hlth Syst, Div Gastroenterol, Dept Med, Philadelphia, PA USA. [Lee, Joon Hyoek] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med, Seoul, South Korea. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 684 BP 532A EP 532A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483802180 ER PT J AU Motola, DL Daneshvar, K York, SR Mullen, A Chung, RT AF Motola, Daniel L. Daneshvar, Kaveh York, Samuel R. Mullen, Alan Chung, Raymond T. TI Highly Efficient Gene Targeting of a LncRNA in Human LX-2 Hepatic Stellate Cells using TALENs 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 [Motola, Daniel L.; Daneshvar, Kaveh; York, Samuel R.; Mullen, Alan; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Mullen, Alan] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 754 BP 565A EP 566A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483802250 ER PT J AU York, SR Zhou, C Chen, JY Daneshvar, K Mullen, A AF York, Samuel R. Zhou, Chan Chen, Jennifer Y. Daneshvar, Kaveh Mullen, Alan TI Identification of long noncoding RNAs induced in hepatic stellate cell myofibroblasts 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 [York, Samuel R.; Zhou, Chan; Chen, Jennifer Y.; Daneshvar, Kaveh; Mullen, Alan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Mullen, Alan] Harvard Stem Cell Inst, Cambridge, MA USA. RI ZHOU, Chan/A-7110-2009 OI ZHOU, Chan/0000-0002-0351-6235 NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 762 BP 569A EP 569A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483802258 ER PT J AU Feeney, ER Mueller, JL Malecki, K King, LY Misdraji, J Corey, KE Chung, RT AF Feeney, Eoin R. Mueller, Jessica L. Malecki, Kyle King, Lindsay Y. Misdraji, Joseph Corey, Kathleen E. Chung, Raymond T. TI Serum soluble CD163 is associated with steatohepatitis and advanced fibrosis in non-alcoholic fatty liver disease 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 [Feeney, Eoin R.; Mueller, Jessica L.; Malecki, Kyle; King, Lindsay Y.; Corey, Kathleen E.; Chung, Raymond T.] Massachusetts Gen Hosp, Div Hepatol, Boston, MA 02114 USA. [Misdraji, Joseph] Massachusetts Gen Hosp, Div Pathol, Boston, MA 02114 USA. [Feeney, Eoin R.; King, Lindsay Y.; Misdraji, Joseph; Corey, Kathleen E.; Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 833 BP 602A EP 602A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483802329 ER PT J AU Basu, P Shah, NJ Aloysius, M AF Basu, Patrick Shah, Niraj J. Aloysius, M. TI Berberine with Alfa Lipoic Acid (ALA) in Non Alcoholic Steato-hepatitis (NASH). A randomized double blinded placebo control trial. A Clinical pilot - The BANISH Trial 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 [Basu, Patrick] Columbia Univ Sch Phys & Surg, New York, NY USA. [Basu, Patrick; Aloysius, M.] Kings Cty Hosp Med Ctr, New York, NY USA. [Shah, Niraj J.] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, New York, NY 10029 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 877 BP 624A EP 624A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483802373 ER PT J AU Backus, LI Belperio, PS Shahoumian, TA Mole, LA AF Backus, Lisa I. Belperio, Pamela S. Shahoumian, Troy A. Mole, Larry A. TI Early Assessment of Hepatitis C Virologic Response of US Veterans Receiving Sofosbuvir-based Therapy 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 [Backus, Lisa I.; Belperio, Pamela S.; Shahoumian, Troy A.; Mole, Larry A.] Vet Affairs Palo Alto Hlth Care Syst, Off Publ Hlth Populat Hlth, Palo Alto, CA USA. [Backus, Lisa I.] VA Palo Alto Healthcare Syst, Dept Med, Palo Alto, CA USA. [Belperio, Pamela S.] VA Greater Los Angeles, Dept Pharm, Los Angeles, CA 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 953 BP 659A EP 659A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803002 ER PT J AU Jimmerson, LC Burton, JR Baouchi, F Truesdale, AE Price, A Ray, M Bushman, L Hammond, K Langness, J Tise, S Everson, GT Kiser, J AF Jimmerson, Leah C. Burton, James R. Baouchi, Fafa Truesdale, Aimee E. Price, Angie Ray, Michelle Bushman, Lane Hammond, Kyle Langness, Jacob Tise, Sarah Everson, Gregory T. Kiser, Jennifer TI Effects of Ribavirin on Red Blood Cell Concentrations of Endogenous Purines in Patients with Hepatitis C Virus Undergoing Ribavirin-Based Treatment 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 [Jimmerson, Leah C.; Ray, Michelle; Bushman, Lane; Hammond, Kyle; Kiser, Jennifer] Univ Colorado, Aurora, CO USA. [Burton, James R.; Langness, Jacob; Tise, Sarah; Everson, Gregory T.] Univ Colorado Hosp, Aurora, CO USA. [Baouchi, Fafa; Truesdale, Aimee E.] Denver Hlth, Digest & Liver Hlth, Denver, CO USA. [Price, Angie] Denver VA Hosp, Denver, CO 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 991 BP 681A EP 682A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803040 ER PT J AU Basu, P Shah, NJ Aloysius, M AF Basu, Patrick Shah, Niraj J. Aloysius, M. TI Simeprevir and Sofosbuvir with modified doses of Ribavirin (RBV) therapy on Telaprevir experienced Co infected (with HIV) cirrhotics with chronic hepatitis C (CHC) A randomized open label clinical pilot study: STOP C 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 [Basu, Patrick] Columbia Univ, Sch Phys & Surg, New York, NY USA. [Basu, Patrick; Aloysius, M.] Kings Cty Hosp, Med Ctr, New York, NY USA. [Shah, Niraj J.] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, New York, NY 10029 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 993 BP 682A EP 683A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803042 ER PT J AU Lin, MV Gogela, NA Wisocky, JL Thiim, M Pratt, DS Andersson, KL Hashemi, N Rutherford, AE Corey, KE Peng, LF Fusco, DN Kim, AY Mullen, A Bloom, JA Chung, RT AF Lin, Ming V. Gogela, Neliswa A. Wisocky, Jessica L. Thiim, Michael Pratt, Daniel S. Andersson, Karin L. Hashemi, Nikroo Rutherford, Anna E. Corey, Kathleen E. Peng, Lee F. Fusco, Dahlene N. Kim, Arthur Y. Mullen, Alan Bloom, Judith A. Chung, Raymond T. TI Real World Experience with Sofosbuvir and Simeprevir combination treatment in patients with HCV genotype 1 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 [Lin, Ming V.; Gogela, Neliswa A.; Wisocky, Jessica L.; Thiim, Michael; Pratt, Daniel S.; Andersson, Karin L.; Corey, Kathleen E.; Peng, Lee F.; Fusco, Dahlene N.; Kim, Arthur Y.; Mullen, Alan; Bloom, Judith A.; Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hashemi, Nikroo; Rutherford, Anna E.] Brigham & Womens Hosp, Boston, MA 02115 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 995 BP 683A EP 684A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803044 ER PT J AU Wedd, JP Ashcraft, B Babson, K Boyd, N Costelow, M Pepe, A Tong, Y Rosen, HR Redington, J AF Wedd, Joel P. Ashcraft, Becky Babson, Kristin Boyd, Nancy Costelow, Marsha Pepe, Anthony Tong, Yvette Rosen, Hugo R. Redington, John TI Treating Advanced Hepatitis C Virus with New Direct Acting Antiviral Medications, a VA Experience 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 [Wedd, Joel P.; Rosen, Hugo R.] Univ Colorado Denver, Aurora, CO USA. [Ashcraft, Becky; Babson, Kristin; Boyd, Nancy; Costelow, Marsha; Pepe, Anthony; Tong, Yvette; Redington, John] Denver VAMC, Denver, CO 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1025 BP 699A EP 699A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803074 ER PT J AU Basu, P Shah, NJ Aloysius, M Brown, RS AF Basu, Patrick Shah, Niraj J. Aloysius, M. Brown, Robert S. TI Interferon ineligible naive chronic hepatitis C genotype I subjects treated with Simeprevir and Sofosbuvir in special population (psychiatric). An open label prospective clinical pilot study; INSPIRE C study 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 [Basu, Patrick; Brown, Robert S.] Columbia Univ, Sch Phys & Surg, New York, NY USA. [Basu, Patrick; Aloysius, M.] Kings Cty Hosp Med Ctr, New York, NY USA. [Shah, Niraj J.] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, New York, NY 10029 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1043 BP 708A EP 708A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803092 ER PT J AU Okada, K Leclair, KB Zhang, YZ Hagen, SJ Cohen, DE AF Okada, Kosuke Leclair, Katherine B. Zhang, Yongzhao Hagen, Susan J. Cohen, David E. TI Thioesterase Superfamily Member 1 (Them1) Suppresses Thermogenesis and Contributes to Diet-Induced Obesity and Non-Alcoholic Fatty Liver Disease (NAFLD) 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 [Okada, Kosuke; Leclair, Katherine B.; Zhang, Yongzhao; Cohen, David E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hagen, Susan J.] Beth Isreal Deaconess Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1115 BP 742A EP 742A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803164 ER PT J AU Xu, J Chi, F Punj, V Lee, WNP French, SW Tsukamoto, H AF Xu, Jun Chi, Feng Punj, Vasu Lee, W. N. Paul French, Samuel W. Tsukamoto, Hidekazu TI Notch1 reprograms mitochondria metabolism for hepatic macrophage M1 activation in ASH through upregulation of pyruvate dehydrogenase (PDH) activity and mtDNA transcription 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 [Xu, Jun; Chi, Feng; Punj, Vasu; Tsukamoto, Hidekazu] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Lee, W. N. Paul; French, Samuel W.] Harbor UCLA Med Ctr, Torrance, CA USA. [Tsukamoto, Hidekazu] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1116 BP 742A EP 742A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803165 ER PT J AU Luther, J King, KR Garber, J Masia, R Motola, DL Yarmush, ML Chung, RT Patel, SJ AF Luther, Jay King, Kevin R. Garber, John Masia, Ricard Motola, Daniel L. Yarmush, Martin L. Chung, Raymond T. Patel, Suraj J. TI Hepatic Gap Junction Inhibition Protects Against Liver Injury and Inflammation in a Murine Model of Alcoholic Steatohepatitis 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 [Luther, Jay; Garber, John; Masia, Ricard; Motola, Daniel L.; Yarmush, Martin L.; Chung, Raymond T.; Patel, Suraj J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [King, Kevin R.] Brigham & Womens Hosp, Boston, MA 02115 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1199 BP 779A EP 780A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803248 ER PT J AU Avruch, JH Bruinsma, BG Weeder, PD Sridharan, GV Yeh, H Uygun, K Markmann, JF AF Avruch, James H. Bruinsma, Bote G. Weeder, Pepijn D. Sridharan, Gautham V. Yeh, Heidi Uygun, Korkut Markmann, James F. TI A novel model for reperfusion of the human liver following organ preservation 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 [Bruinsma, Bote G.; Weeder, Pepijn D.; Sridharan, Gautham V.; Uygun, Korkut] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [Avruch, James H.; Yeh, Heidi; Markmann, James F.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1312 BP 830A EP 830A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803360 ER PT J AU Platt, HL Citti, CC Minguez, B Chen, TY Ventura-Cots, M Hernandez, MD Jalali, Z Badshah, MB Yin, M Aytaman, A Nelson, M Rockstroh, JK Goetz, MB Schwartz, M Dieterich, D Aberg, J Hoshida, Y Brau, N AF Platt, Heather L. Citti, Caitlin C. Minguez, Beatriz Chen, Ting-Yi Ventura-Cots, Meritxell Hernandez, Maria D. Jalali, Ziba Badshah, Maaz B. Yin, Michael Aytaman, Ayse Nelson, Mark Rockstroh, Juergen K. Goetz, Matthew B. Schwartz, Myron Dieterich, Douglas Aberg, Judith Hoshida, Yujin Braeu, Norbert TI Liver Transplantation for HIV-Infected Patients with Hepatocellular Carcinoma (HCC) 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 [Platt, Heather L.; Yin, Michael] Columbia Univ, Med Ctr, Div Infect Dis, New York, NY USA. [Citti, Caitlin C.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Minguez, Beatriz; Ventura-Cots, Meritxell] Hosp Univ Vall dHebron, Barcelona, Spain. [Chen, Ting-Yi] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Hernandez, Maria D.] Univ Miami, Miami, FL USA. [Jalali, Ziba] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Jalali, Ziba] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Badshah, Maaz B.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Aytaman, Ayse] VA New York Harbor HCS, Brooklyn, NY USA. [Aytaman, Ayse] SUNY Downstate Hlth Sci Ctr, Brooklyn, NY USA. [Nelson, Mark] Chelsea & Westminster Hosp, London, England. [Rockstroh, Juergen K.] Univ Klinikum Bonn, Bonn, Germany. [Goetz, Matthew B.] VA Greater Los Angeles HCS, Los Angeles, CA USA. [Schwartz, Myron] Icahn Sch Med Mt Sinai, Div Hepatobiliary Surg, New York, NY 10029 USA. [Dieterich, Douglas; Aberg, Judith; Hoshida, Yujin; Braeu, Norbert] Icahn Sch Med Mt Sinai, Div Infect Dis & Liver Dis, New York, NY 10029 USA. [Braeu, Norbert] James J Peters VA Med Ctr, Bronx, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1320 BP 834A EP 834A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803368 ER PT J AU Chen, TY Merchante, N Citti, CC Platt, HL Badshah, MB Ventura-Cots, M Merino, E Kikuchi, L Jain, MK Rodriguez-Arrondo, F Minguez, B Yin, M Aytaman, A Tural, C Schwartz, M Dieterich, D Aberg, J Pineda, J Marrero, JA Sherman, M Hoshida, Y Brau, N AF Chen, Ting-Yi Merchante, Nicolas Citti, Caitlin C. Platt, Heather L. Badshah, Maaz B. Ventura-Cots, Meritxell Merino, Esperanza Kikuchi, Luciana Jain, Mamta K. Rodriguez-Arrondo, Francisco Minguez, Beatriz Yin, Michael Aytaman, Ayse Tural, Cristina Schwartz, Myron Dieterich, Douglas Aberg, Judith Pineda, Juan Marrero, Jorge A. Sherman, Morris Hoshida, Yujin Braeu, Norbert TI Predicting Survival of HIV-Infected Patients with Liver Cancer - the SHILCA Score and Staging Model 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 [Chen, Ting-Yi; Jain, Mamta K.; Marrero, Jorge A.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Merchante, Nicolas; Pineda, Juan] Hosp Univ Valme, Seville, Spain. [Citti, Caitlin C.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Platt, Heather L.; Yin, Michael] Columbia Univ, Med Ctr, Div Infect Dis, New York, NY USA. [Badshah, Maaz B.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Ventura-Cots, Meritxell; Minguez, Beatriz] Hosp Univ Vall dHebron, Barcelona, Spain. [Merino, Esperanza] Hosp Gen Univ Alicante, Alicante, Spain. [Kikuchi, Luciana] Univ Sao Paulo, Sao Paulo, Brazil. [Aytaman, Ayse] VA New York Harbor HCS, Brooklyn, NY USA. [Tural, Cristina] Hosp Badalona Germans Trias & Pujol, Barcelona, Spain. [Schwartz, Myron] Icahn Sch Med Mt Sinai, Div Hepatobiliary Surg, New York, NY 10029 USA. [Dieterich, Douglas; Hoshida, Yujin; Braeu, Norbert] Icahn Sch Med Mt Sinai, Div Liver Dis, New York, NY 10029 USA. [Rodriguez-Arrondo, Francisco] Hosp Univ Donostia, San Sebastian, Spain. [Dieterich, Douglas; Aberg, Judith] Icahn Sch Med Mt Sinai, Div Infect Dis, New York, NY 10029 USA. [Sherman, Morris] Toronto Gen Hosp, Toronto, ON, Canada. [Sherman, Morris] Univ Toronto, Toronto, ON, Canada. [Braeu, Norbert] James J Peters VA Med Ctr, Bronx, NY 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 1322 BP 835A EP 835A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803370 ER PT J AU Jou, JH Beste, LA Yang, Y Chang, MF Muir, AJ AF Jou, Janice H. Beste, Lauren A. Yang, Yin Chang, Michael F. Muir, Andrew J. TI Specialty Care is Associated with Early Diagnosis of Hepatitis C-related Hepatocellular Carcinoma in US Veterans 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 [Jou, Janice H.; Chang, Michael F.] Portland VA Med Ctr, Portland, OR USA. [Beste, Lauren A.; Yang, Yin] Puget Sound VA Med Ctr, Seattle, WA USA. [Muir, Andrew J.] Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1330 BP 839A EP 839A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803378 ER PT J AU Kaplan, DE Aytaman, A Baytarian, M D'Addeo, K Dai, F Fox, RK Hunt, KK Knott, A Mehta, R Pedrosa, M Pocha, C Skanderson, M Valderama, A Taddei, TH AF Kaplan, David E. Aytaman, Ayse Baytarian, Michelle D'Addeo, Kathryn Dai, Feng Fox, Rena K. Hunt, Kristel K. Knott, Astrid Mehta, Rajni Pedrosa, Marcos Pocha, Christine Skanderson, Melissa Valderama, Adriana Taddei, Tamar H. TI Subgroup Analysis of Patients with HIV plus HCC Among a Cohort of 2322 Veterans Diagnosed with Hepatocellular Carcinoma (HCC) from 2008-2010 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 [Kaplan, David E.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [D'Addeo, Kathryn; Dai, Feng; Mehta, Rajni; Taddei, Tamar H.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Aytaman, Ayse] VA New York Harbor Hlth Care Syst, New York, NY USA. [Baytarian, Michelle; Pedrosa, Marcos] Boston VA Healthcare Syst, Boston, MA USA. [Fox, Rena K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Hunt, Kristel K.] James J Peters VA Med Ctr, New York, NY USA. [Knott, Astrid; Pocha, Christine] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA. [Skanderson, Melissa] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Valderama, Adriana] Bayer Healthcare Pharmaceut, Wayne, NJ 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1372 BP 858A EP 859A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803420 ER PT J AU Citti, CC Platt, HL Badshah, MB Chen, TY Kikuchi, L Ventura-Cots, M Chaudhary, N Marcus, S Yin, M Aytaman, A Aberg, J Schwartz, M Dieterich, D Hoshida, Y Brau, N AF Citti, Caitlin C. Platt, Heather L. Badshah, Maaz B. Chen, Ting-Yi Kikuchi, Luciana Ventura-Cots, Meritxell Chaudhary, Noami Marcus, Sonja Yin, Michael Aytaman, Ayse Aberg, Judith Schwartz, Myron Dieterich, Douglas Hoshida, Yujin Braeu, Norbert TI HIV Viral Load Independently Predicts Survival in HIV-Infected Patients With Hepatocellular Carcinoma (HCC) 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 [Citti, Caitlin C.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Platt, Heather L.; Yin, Michael] Columbia Univ Med Ctr, Div Infect Dis, New York, NY USA. [Badshah, Maaz B.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Chen, Ting-Yi] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Kikuchi, Luciana] Univ Sao Paulo, Sao Paulo, Brazil. [Ventura-Cots, Meritxell] Hosp Univ Vall dHebron, Barcelona, Spain. [Chaudhary, Noami] NYU Med Ctr, New York, NY USA. [Marcus, Sonja; Braeu, Norbert] James J Peters VA Med Ctr, Bronx, NY USA. [Aytaman, Ayse] VA New York Harbor HCS, Brooklyn, NY USA. [Aytaman, Ayse] SUNY Downstate Hlth Sci Ctr, Brooklyn, NY USA. [Aberg, Judith; Dieterich, Douglas; Hoshida, Yujin; Braeu, Norbert] Icahn Sch Med Mt Sinai, Div Infect Dis & Liver Dis, New York, NY 10029 USA. [Schwartz, Myron] Icahn Sch Med Mt Sinai, Div Hepatobiliary Surg, New York, NY 10029 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1391 BP 867A EP 868A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803438 ER PT J AU Li, YH Kaplan, DE AF Li, Yonghai Kaplan, David E. TI In vitro validation of human glypican-3 specific chimeric antigen receptors for hepatocellular carcinoma 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 [Kaplan, David E.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Li, Yonghai; Kaplan, David E.] Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1397 BP 870A EP 870A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483803444 ER PT J AU King, LY Canasto-Chibuque, C Johnson, KB Yip, S Chen, XT Kojima, K Deshmukh, M Venkatesh, A Tan, PS Sun, XC Villanueva, A Sangiovanni, A Nair, V Mahajan, M Kobayashi, M Kumada, H Iavarone, M Colombo, M Fiel, MI Friedman, SL Llovet, JM Chung, R Hoshida, Y AF King, Lindsay Y. Canasto-Chibuque, Claudia Johnson, Kara B. Yip, Shun Chen, Xintong Kojima, Kensuke Deshmukh, Manjeet Venkatesh, Anu Tan, Poh Seng Sun, Xiaochen Villanueva, Augusto Sangiovanni, Angelo Nair, Venugopalan Mahajan, Milind Kobayashi, Masahiro Kumada, Hiromitsu Iavarone, Massimo Colombo, Massimo Fiel, M. Isabel Friedman, Scott L. Llovet, Josep M. Chung, Raymond Hoshida, Yujin TI A genomic and clinical prognostic index for hepatitis C-related early-stage cirrhosis 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 [Canasto-Chibuque, Claudia; Chen, Xintong; Kojima, Kensuke; Deshmukh, Manjeet; Venkatesh, Anu; Tan, Poh Seng; Sun, Xiaochen; Friedman, Scott L.; Llovet, Josep M.; Hoshida, Yujin] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Liver Canc Program, New York, NY 10029 USA. [King, Lindsay Y.; Johnson, Kara B.; Yip, Shun; Chung, Raymond] Harvard Univ, Sch Med, Ctr Liver, Boston, MA USA. [King, Lindsay Y.; Johnson, Kara B.; Yip, Shun; Chung, Raymond] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Div,Dept Med, Boston, MA USA. [Tan, Poh Seng] Natl Univ Hlth Syst, Div Gastroenterol & Hepatol, Univ Med Cluster, Singapore, Singapore. [Villanueva, Augusto] Kings Coll London, Inst Liver Sci, London WC2R 2LS, England. [Sangiovanni, Angelo; Iavarone, Massimo; Colombo, Massimo] Univ Milan, Div Gastroenterol, M&A Migliavacca Ctr Liver Dis, Milan, Italy. [Nair, Venugopalan; Fiel, M. Isabel] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Mahajan, Milind] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, New York, NY 10029 USA. [Kobayashi, Masahiro; Kumada, Hiromitsu] Toranomon Gen Hosp, Tokyo, Japan. [Llovet, Josep M.] Hosp Clin Barcelona, HCC Translat Res Lab, Barcelona Clin Liver Canc Grp, Barcelona, Spain. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1476 BP 908A EP 908A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804039 ER PT J AU Wurcel, AG Superson, M Noonan, K Kim, AY McGovern, BH AF Wurcel, Alysse G. Superson, Michaela Noonan, Kathryn Kim, Arthur Y. McGovern, Barbara H. TI Burden of Hepatitis C Virus and Chronic Liver Disease amongst Hospitalized Inmates in Massachusetts 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 [Wurcel, Alysse G.; McGovern, Barbara H.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Kim, Arthur Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Superson, Michaela; Noonan, Kathryn] Lemuel Shattuck Hosp, Jamaica Plain, MA USA. [McGovern, Barbara H.] AbbVie, N Chicago, IL USA. [Superson, Michaela] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1508 BP 923A EP 924A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804071 ER PT J AU Beste, LA Green, P Ioannou, GN AF Beste, Lauren A. Green, Pamela Ioannou, George N. TI Boceprevir and telaprevir-based regimens for the treatment of hepatitis C virus in a real world HIV/HCV co-infected cohort 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 [Beste, Lauren A.] VA Puget Sound Hlth Care Syst, Internal Med, Seattle, WA USA. [Beste, Lauren A.; Ioannou, George N.] Univ Washington, Seattle, WA 98195 USA. [Ioannou, George N.] VA Puget Sound Hlth Care Syst, Gastroenterol, Seattle, WA USA. [Green, Pamela] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1525 BP 932A EP 933A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804088 ER PT J AU Rajbhandari, R Juncadella, AC Rubin, AK Ajayi, T Wu, Y Ananthakrishnan, AN Chung, RT AF Rajbhandari, Ruma Juncadella, Anna C. Rubin, Anna K. Ajayi, Tokunbo Wu, Ying Ananthakrishnan, Ashwin N. Chung, Raymond T. TI Inadequate Hepatitis B Care in Mothers After Pregnancy 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 [Rajbhandari, Ruma; Wu, Ying; Ananthakrishnan, Ashwin N.; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Rajbhandari, Ruma; Juncadella, Anna C.; Rubin, Anna K.; Wu, Ying; Ananthakrishnan, Ashwin N.; Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. [Juncadella, Anna C.; Rubin, Anna K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Ajayi, Tokunbo] Salem Hosp, Dept Med, Salem, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1552 BP 945A EP 945A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804115 ER PT J AU Tapper, EB Finkelstein, D Piatkowski, G Mittleman, M Lai, M AF Tapper, Elliot B. Finkelstein, Dan Piatkowski, Gail Mittleman, Murray Lai, Michelle TI A quality improvement initiative decreases 30-day readmission rates in patients admitted to a Hepatology Service 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 [Tapper, Elliot B.; Piatkowski, Gail; Mittleman, Murray; Lai, Michelle] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Finkelstein, Dan] Massachusetts Gen Hosp, Stat Core, Boston, MA 02114 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1554 BP 946A EP 946A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804117 ER PT J AU Beste, LA Pichler, R Germani, M Chang, MF Young, B AF Beste, Lauren A. Pichler, Raimund Germani, Maureen Chang, Michael F. Young, Bessie TI Telehepatology improves provider satisfaction and specialty care integration among rural Veterans Affairs Primary Care Providers 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 [Beste, Lauren A.] VA Puget Sound Hlth Care Syst, Internal Med, Seattle, WA USA. [Beste, Lauren A.; Pichler, Raimund; Young, Bessie] Univ Washington, Seattle, WA 98195 USA. [Pichler, Raimund; Young, Bessie] VA Puget Sound Hlth Care Syst, Nephrol, Seattle, WA USA. [Germani, Maureen] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Chang, Michael F.] Portland VA Med Ctr, Portland, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1578 BP 958A EP 958A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804141 ER PT J AU Zickmund, SL Chapko, MK Hanusa, BH Youk, AO Switzer, GE Sevick, MA Obrosky, DS Bayliss, NK Zook, CL Arnold, RA AF Zickmund, Susan L. Chapko, Michael K. Hanusa, Barbara H. Youk, Ada O. Switzer, Galen E. Sevick, Mary Ann Obrosky, David S. Bayliss, Nichole K. Zook, Carolyn L. Arnold, Robert A. TI Predictors of Attendance at the Gastroenterology Clinic to Discuss Treatment for Hepatitis C 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 [Zickmund, Susan L.; Youk, Ada O.; Switzer, Galen E.; Arnold, Robert A.] Univ Pittsburgh, Pittsburgh, PA USA. [Zickmund, Susan L.; Hanusa, Barbara H.; Youk, Ada O.; Switzer, Galen E.; Obrosky, David S.] VA Pittsburgh Healthcare Syst, Res, Pittsburgh, PA USA. [Chapko, Michael K.] VA Puget Sound Healthcare Syst, Res, Seattle, WA USA. [Bayliss, Nichole K.] Chatham Univ, Pittsburgh, PA USA. [Sevick, Mary Ann] NYU, New York, NY USA. [Zook, Carolyn L.] Oregon Hlth & Sci Univ, Portland, OR 97201 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1580 BP 959A EP 959A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804143 ER PT J AU Zickmund, SL Chapko, MK Hanusa, BH Youk, AO Switzer, GE Sevick, MA Bayliss, NK Zook, CL Obrosky, DS Arnold, RA AF Zickmund, Susan L. Chapko, Michael K. Hanusa, Barbara H. Youk, Ada O. Switzer, Galen E. Sevick, Mary Ann Bayliss, Nichole K. Zook, Carolyn L. Obrosky, David S. Arnold, Robert A. TI Barriers to Initiating Treatment for Hepatitis C: Results of a Veteran Population 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 [Zickmund, Susan L.; Youk, Ada O.; Switzer, Galen E.; Arnold, Robert A.] Univ Pittsburgh, Pittsburgh, PA USA. [Zickmund, Susan L.; Hanusa, Barbara H.; Youk, Ada O.; Switzer, Galen E.; Obrosky, David S.] VA Pittsburgh Healthcare Syst, Res, Pittsburgh, PA USA. [Chapko, Michael K.] VA Puget Sound Healthcare Syst, Res, Seattle, WA USA. [Sevick, Mary Ann] NYU, New York, NY USA. [Bayliss, Nichole K.] Chatham Univ, Pittsburgh, PA USA. [Zook, Carolyn L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 1586 BP 961A EP 962A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804149 ER PT J AU Lau, D Ganova-Raeva, L Chung, RT Johnson, G Chang, KM Lisker-Melman, M Shaikh, OS Janssen, HL Wahed, AS Lok, AS AF Lau, Daryl Ganova-Raeva, Lilia Chung, Raymond T. Johnson, Geoffrey Chang, Kyong-Mi Lisker-Melman, Mauricio Shaikh, Obaid S. Janssen, Harry L. Wahed, Abdus S. Lok, Anna S. TI Prevalence of Precore and Dual Basal Core Promoter HBV Variants in a Racially Diverse Cohort of Patients with Chronic HBV Infection in North America 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 [Lau, Daryl] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [Ganova-Raeva, Lilia] CDC, Atlanta, GA 30333 USA. [Chung, Raymond T.] Harvard Univ, Sch Med, MGH, Boston, MA USA. [Johnson, Geoffrey; Shaikh, Obaid S.; Wahed, Abdus S.] Univ Pittsburgh, Pittsburgh, PA USA. [Chang, Kyong-Mi] Philadelphia VAMC, Philadelphia, PA USA. [Chang, Kyong-Mi] Univ Penn, Philadelphia, PA 19104 USA. [Lisker-Melman, Mauricio] Washington Univ, Sch Med, St Louis, MO USA. [Janssen, Harry L.] Toronto Western Hosp, Univ Hlth Network, Toronto, ON M5T 2S8, Canada. [Lok, Anna S.] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 1605 BP 970A EP 971A PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804168 ER PT J AU Backus, LI Belperio, PS Loomis, TP Mole, LA AF Backus, Lisa I. Belperio, Pamela S. Loomis, Timothy P. Mole, Larry A. TI Hepatitis B Screening and Prevalence among High-Risk Populations within the Department of Veterans Affairs 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 [Backus, Lisa I.; Belperio, Pamela S.; Loomis, Timothy P.; Mole, Larry A.] Off Publ Hlth Populat Hlth, Dept Vet Affairs, Palo Alto, CA USA. [Backus, Lisa I.] Vet Affairs Palo Alto Healthcare Syst, Dept Med, Palo Alto, CA USA. [Belperio, Pamela S.] Vet Affairs Greater Los Angeles, Dept Pharm, Los Angeles, CA 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1611 BP 973A EP 973A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804174 ER PT J AU Kushner, T Kaplan, DE AF Kushner, Tatyana Kaplan, David E. TI Delta Hepatitis Within the Veterans Affairs Medical System 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 [Kaplan, David E.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Kushner, Tatyana; Kaplan, David E.] Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1612 BP 974A EP 974A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804175 ER PT J AU Rajbhandari, R Chung, RT Ananthakrishnan, AN AF Rajbhandari, Ruma Chung, Raymond T. Ananthakrishnan, Ashwin N. TI HBV infection is associated with greater mortality in hospitalized patients compared to HCV infection or alcoholic liver disease 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 [Rajbhandari, Ruma; Chung, Raymond T.; Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Rajbhandari, Ruma; Chung, Raymond T.; Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 1689 BP 1010A EP 1011A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804251 ER PT J AU Rajbhandari, R Chung, RT Khalili, H Ananthakrishnan, AN AF Rajbhandari, Ruma Chung, Raymond T. Khalili, Hamed Ananthakrishnan, Ashwin N. TI HBV/HIV coinfection is associated with greater mortality in hospitalized patients with HBV 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 [Rajbhandari, Ruma; Chung, Raymond T.; Khalili, Hamed; Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Boston, MA 02114 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1687 BP 1010A EP 1010A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804249 ER PT J AU Wright, AJ Kim, AY Fishman, JA Linas, BP Chung, RT AF Wright, Alissa J. Kim, Arthur Y. Fishman, Jay A. Linas, Benjamin P. Chung, Raymond T. TI Pre-transplant sofosbuvir and ribavirin for patients with advanced liver disease and chronic hepatitis C awaiting deceased donor liver transplantation: A cost-effectiveness analysis 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 [Wright, Alissa J.; Kim, Arthur Y.; Fishman, Jay A.; Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Linas, Benjamin P.] Boston Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 5 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 1758 BP 1045A EP 1045A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804320 ER PT J AU Zhu, CL Hong, J Fusco, D Brisac, C Schaefer, EA Jeong, SW Peng, LF Lin, WY Chung, RT AF Zhu, Chuanlong Hong, Jian Fusco, Dahlene Brisac, Cynthia Schaefer, Esperance A. Jeong, Soung Wong Peng, Lee F. Lin, Wenyu Chung, Raymond T. TI EFTUD2 alters hepatitis C virus replication by modulating the RIG-I/MDA5 pathway 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 [Zhu, Chuanlong] Anhui Med Univ, Anhui Prov Hosp, Dept Infect Dis, Hefei, Peoples R China. [Zhu, Chuanlong; Hong, Jian; Fusco, Dahlene; Brisac, Cynthia; Schaefer, Esperance A.; Jeong, Soung Wong; Peng, Lee F.; Lin, Wenyu; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1765 BP 1048A EP 1049A PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804327 ER PT J AU Schaefer, EA Meixiong, J Motola, DL Fusco, D Brisac, C Salloum, S Luther, J Lin, WY McGowan, MP Peng, LF Chung, RT AF Schaefer, Esperance A. Meixiong, James Motola, Daniel L. Fusco, Dahlene Brisac, Cynthia Salloum, Shadi Luther, Jay Lin, Wenyu McGowan, Mary P. Peng, Lee F. Chung, Raymond T. TI Mipomersen, an FDA-approved anti-sense inhibitor of apoB100, has anti-HCV effect in-vitro 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 [Schaefer, Esperance A.; Meixiong, James; Motola, Daniel L.; Fusco, Dahlene; Brisac, Cynthia; Salloum, Shadi; Luther, Jay; Lin, Wenyu; Peng, Lee F.; Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McGowan, Mary P.] Genzyme, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1769 BP 1050A EP 1050A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804331 ER PT J AU Lin, WY Hong, J Zhu, CL Fusco, D Schaefer, EA Brisac, C Peng, LF Chung, RT AF Lin, Wenyu Hong, Jian Zhu, Chuanlong Fusco, Dahlene Schaefer, Esperance A. Brisac, Cynthia Peng, Lee F. Chung, Raymond T. TI The anti-HCV gene SART1 regulates EIF4G3 and GORASP2 expression through exon splicing 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 [Lin, Wenyu; Hong, Jian; Zhu, Chuanlong; Fusco, Dahlene; Schaefer, Esperance A.; Brisac, Cynthia; Peng, Lee F.; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1786 BP 1058A EP 1058A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804348 ER PT J AU Harwood, NM Golden-Mason, L Rosen, HR Mengshol, JA AF Harwood, Noah M. Golden-Mason, Lucy Rosen, Hugo R. Mengshol, John A. TI Full Length and Subgenomic HCV Infection, Endosomal TLR Stimulation, and Differentiation Increase Macrophage Immunoregulatory Galectin-9 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 [Harwood, Noah M.; Golden-Mason, Lucy; Rosen, Hugo R.; Mengshol, John A.] Univ Colorado SOM, Denver VA Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 1820 BP 1073A EP 1074A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804382 ER PT J AU Brisac, C Salloum, S Chevaliez, S Feeney, ER Schaefer, EA Zhu, CL Hong, J Fusco, D Peng, LF Lin, WY Chung, RT AF Brisac, Cynthia Salloum, Shadi Chevaliez, Stephane Feeney, Eoin R. Schaefer, Esperance A. Zhu, Chuanlong Hong, Jian Fusco, Dahlene Peng, Lee F. Lin, Wenyu Chung, Raymond T. TI The Scaffold Protein IQGAP2 is Essential for the Innate Control of HCV Infection in Hepatoma Cells 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 [Brisac, Cynthia; Salloum, Shadi; Feeney, Eoin R.; Schaefer, Esperance A.; Zhu, Chuanlong; Hong, Jian; Fusco, Dahlene; Peng, Lee F.; Lin, Wenyu; Chung, Raymond T.] Massachusetts Gen Hosp, Med GI Unit, Boston, MA 02114 USA. [Chevaliez, Stephane] Henry Mondor Hosp, Creteil, France. [Chevaliez, Stephane] Henry Mondor Hosp, INSERM, UnitU955, Creteil, France. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1825 BP 1076A EP 1076A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804387 ER PT J AU Chen, DY Robilotti, B Matsubara, LK Brown, J Aneja, J Kulaga, S Lewis-Ximenez, L James, EA Kwok, WW Kim, AY Lauer, GM AF Chen, Diana Y. Robilotti, Brandon Matsubara, Lyndon K. Brown, Joelle Aneja, Jasneet Kulaga, Stephanie Lewis-Ximenez, Lia James, Eddie A. Kwok, William W. Kim, Arthur Y. Lauer, Georg M. TI Increased Frequency of CD39+HCV-Specific CD4 T cells Correlates with Progression to Chronic Hepatitis C 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 [Chen, Diana Y.; Robilotti, Brandon; Matsubara, Lyndon K.; Brown, Joelle; Lauer, Georg M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Aneja, Jasneet; Kulaga, Stephanie; Kim, Arthur Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. [Lewis-Ximenez, Lia] Inst Oswaldo Cruz, Dept Virol, BR-20001 Rio De Janeiro, Brazil. [James, Eddie A.; Kwok, William W.] Virginia Mason, Benaroya Res Inst, Seattle, WA 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1833 BP 1080A EP 1080A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483804395 ER PT J AU Doehle, B Gontcharova, V Chodavarapu, RK McNally, J Chung, RT Everson, GT McHutchison, JG Miller, MD Mo, HM AF Doehle, Brian Gontcharova, Viktoria Chodavarapu, Ramakrishna K. McNally, John Chung, Raymond T. Everson, Gregory T. McHutchison, John G. Miller, Michael D. Mo, Hongmei TI Resistance Analysis of Treatment-Naive HCV Genotype 1-6 Infected Patients Treated with Sofosbuvir in Combination with GS-5816 for 12 Weeks 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 [Doehle, Brian; Gontcharova, Viktoria; Chodavarapu, Ramakrishna K.; McNally, John; McHutchison, John G.; Miller, Michael D.; Mo, Hongmei] Gilead Sci Inc, Foster City, CA 94404 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Everson, Gregory T.] Univ Colorado Denver, Aurora, CO 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PY 2014 VL 60 SU 1 SI SI MA 1942 BP 1138A EP 1139A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483805017 ER PT J AU Chung, RT Lauer, GM Stamm, LM Liu, L Mo, HM Pang, PS Brainard, DM McHutchison, JG Kim, AY AF Chung, Raymond T. Lauer, Georg M. Stamm, Luisa M. Liu, Lin Mo, Hongmei Pang, Phillip S. Brainard, Diana M. McHutchison, John G. Kim, Arthur Y. TI Ledipasvir/Sofosbuvir is Safe and Effective in Nosocomially Infected Patients with Advanced Age and Significant Cardiac Co-Morbidities 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 [Chung, Raymond T.; Lauer, Georg M.; Kim, Arthur Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stamm, Luisa M.; Liu, Lin; Mo, Hongmei; Pang, Phillip S.; Brainard, Diana M.; McHutchison, John G.] Gilead Sci Inc, Foster City, CA 94404 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 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 1970 BP 1158A EP 1158A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS8EW UT WOS:000344483805045 ER PT J AU Bianchi, MT Lipoma, T Darling, C Alameddine, Y Westover, MB AF Bianchi, M. T. Lipoma, T. Darling, C. Alameddine, Y. Westover, M. B. TI Automated Sleep Apnea Quantification Based on Respiratory Movement SO INTERNATIONAL JOURNAL OF MEDICAL SCIENCES LA English DT Article DE algorithm; prediction; respiration; classification; sleep apnea ID COST-EFFECTIVENESS ANALYSIS; MONITORING DEVICE; HOME; DIAGNOSIS; POLYSOMNOGRAPHY; PRESSURE; OXIMETRY; SENSOR; RISK AB Obstructive sleep apnea (OSA) is a prevalent and treatable disorder of neurological and medical importance that is traditionally diagnosed through multi-channel laboratory polysomnography(PSG). However, OSA testing is increasingly performed with portable home devices using limited physiological channels. We tested the hypothesis that single channel respiratory effort alone could support automated quantification of apnea and hypopnea events. We developed a respiratory event detection algorithm applied to thoracic strain-belt data from patients with variable degrees of sleep apnea. We optimized parameters on a training set (n=57) and then tested performance on a validation set (n=59). The optimized algorithm correlated significantly with manual scoring in the validation set (R-2=0.73 for training set, R-2=0.55 for validation set; p<0.05). For dichotomous classification, the AUC was >0.92 and >0.85 using apnea-hypopnea index cutoff values of 5 and 15, respectively. Our findings demonstrate that manually scored AHI values can be approximated from thoracic movements alone. This finding has potential applications for automating laboratory PSG analysis as well as improving the performance of limited channel home monitors. C1 [Alameddine, Y.; Westover, M. B.] Massachusetts Gen Hosp, Dept Neurol, Sleep Div, Boston, MA 02114 USA. [Bianchi, M. T.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. [Lipoma, T.; Darling, C.] Rest Devices, Boston, MA USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Wang 7 Neurol,55 Fruit St, Boston, MA 02114 USA. EM mtbianchi@partners.org FU department of Neurology, Massachusetts General Hospital; Center for Integration of Medicine and Innovative Technology; Harvard Catalyst KL2 Medical Research Investigator Fellowship; American Brain Foundation FX Dr Bianchi has received support from the department of Neurology, Massachusetts General Hospital, the Young Clinician Award from the Center for Integration of Medicine and Innovative Technology, and the Harvard Catalyst KL2 Medical Research Investigator Fellowship. Dr. Westover received support from the American Brain Foundation. NR 30 TC 0 Z9 0 U1 0 U2 3 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-1907 J9 INT J MED SCI JI Int. J. Med. Sci. PY 2014 VL 11 IS 8 BP 796 EP 802 DI 10.7150/ijms.9303 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA AT0OY UT WOS:000344636300006 PM 24936142 ER PT J AU Shore, P Goranson, A Ward, MF Lu, MW AF Shore, Peter Goranson, Anders Ward, Mark F. Lu, Mary W. TI MEETING VETERANS WHERE THEY'RE @: A VA HOME-BASED TELEMENTAL HEALTH (HBTMH) PILOT PROGRAM SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE LA English DT Article DE telemedicine; telehealth; videoconference; behavioral medicine; veterans AB Objectives: The first Home-Based Telemental pilot program (HBTMH) in the Department of Veterans Affairs addresses the significant challenge of access to mental health treatment for rural veterans. Though the feasibility of telemental healthcare in clinic-based settings has been well documented, the feasibility of telemental health via webcam and computer in a patient's home or other non-clinic settings is unknown. Methods: The HBTMH program, established in December 2009 at the Portland VA Medical Center, delivers a wide range of mental health services into the homes and other non-clinic settings of rural veterans via webcam, secure and encrypted software and veteran-owned personal computers. The program adhered to a Standard Operating Procedure (SOP) Manual, evaluated patients with the Assessment for Suitability for Home Based Telemental Health (ASH-25), utilized a Patient Support Person (PSP), and incorporated a peer technical consultant to provide assistance to veterans. The authors describe satisfaction and safety survey results from the initial 40 veterans enrolled. Results: Survey results support the feasibility and safety of using webcams, secure/encrypted software and veteran-owned personal computers for the delivery of mental health services into the home. Veterans report high levels of satisfaction and perceived safety with home-based telemental health. Results also suggest fewer no-show appointments in home-based telemental health compared to clinic-based telemental health. Conclusions: The authors discuss the strength and limitations of the program as well as potential areas of future research. C1 [Shore, Peter; Goranson, Anders; Ward, Mark F.; Lu, Mary W.] Portland VA Med Ctr, Portland, OR 97239 USA. [Shore, Peter; Goranson, Anders; Lu, Mary W.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Shore, P (reprint author), Portland VA Med Ctr, Dept Vet Affairs, 3710 SW US Vet Hosp Rd P3TELH, Portland, OR 97239 USA. EM shore@ohsu.edu FU Pacific Northwest Mental Illness Research and Education and Clinical Center (MIRECC) FX This work was partially supported by the Pacific Northwest Mental Illness Research and Education and Clinical Center (MIRECC). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 8 TC 4 Z9 4 U1 0 U2 3 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, PO BOX 337, AMITYVILLE, NY 11701 USA SN 0091-2174 EI 1541-3527 J9 INT J PSYCHIAT MED JI Int. J. Psychiatr. Med. PY 2014 VL 48 IS 1 BP 5 EP 17 DI 10.2190/PM.48.1.b PG 13 WC Psychiatry SC Psychiatry GA AT3IZ UT WOS:000344830100002 PM 25354923 ER PT J AU Hernandez-Tejada, MA Zoller, JS Ruggiero, KJ Kazley, AS Acierno, R AF Hernandez-Tejada, Melba A. Zoller, James S. Ruggiero, Kenneth J. Kazley, Abby Swanson Acierno, Ron TI EARLY TREATMENT WITHDRAWAL FROM EVIDENCE-BASED PSYCHOTHERAPY FOR PTSD: TELEMEDICINE AND IN-PERSON PARAMETERS SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE LA English DT Article DE attrition; telemedicine; psychotherapy; PTSD ID POSTTRAUMATIC-STRESS-DISORDER; PROLONGED EXPOSURE THERAPY; COGNITIVE-BEHAVIORAL THERAPY; EYE-MOVEMENT DESENSITIZATION; PROCESSING THERAPY; PSYCHOLOGICAL TREATMENTS; CONTROLLED-TRIAL; ASSAULT VICTIMS; RAPE VICTIMS; VETERANS AB Objective: To determine differences in reported barriers to treatment completion associated with telemedicine vs. in-person delivery of evidence-based treatment for PTSD in combat veterans. Method: The present study was derived from two ongoing randomized controlled trials (RCTs) comparing in-person vs. telemedicine delivery of exposure therapy for PTSD. A one-time telephone assessment of participants who dropped out from the treatment phase of these two studies was conducted, with measures focusing on reported reasons for dropout, and perceived comfort and efficacy of the treatment modality. Dichotomous data were analyzed via chi-square and logistic regression; continuous data via ANOVA. Results: Forty-seven of 69 total dropouts participated. There was no difference in rate of dropout between modalities. A greater proportion of participants receiving in-person exposure therapy reported difficulties with logistical aspects of care (e.g., parking), whereas a greater proportion of participants receiving telemedicine therapy reported difficulty tolerating certain stressful aspects of treatment; however, those receiving telemedicine delivered treatment completed more sessions before dropping out. Participants in both conditions reported that they liked and were confident in their therapist Conclusions: Dropout reasons varied according to type of treatment delivery. Recommendations for future research are given in terms of modification of treatment protocol according to delivery modality. C1 [Hernandez-Tejada, Melba A.; Zoller, James S.; Ruggiero, Kenneth J.; Kazley, Abby Swanson; Acierno, Ron] Med Univ S Carolina, Johns Isl, SC 29455 USA. [Ruggiero, Kenneth J.; Acierno, Ron] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Hernandez-Tejada, MA (reprint author), Med Univ S Carolina, 2505 Watercrest Lane, Johns Isl, SC 29455 USA. EM hernanma@musc.edu FU Veterans Affairs Health Services Research and Development [NCT01102764]; Department of Defense [PT073980] FX This work was supported by a grant from Veterans Affairs Health Services Research and Development awarded to R. Acierno (NCT01102764) and a grant from the Department of Defense (PT073980). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs, Department of Defense, or the United States government. There are no conflicts of interest to disclose. NR 56 TC 5 Z9 5 U1 1 U2 6 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, PO BOX 337, AMITYVILLE, NY 11701 USA SN 0091-2174 EI 1541-3527 J9 INT J PSYCHIAT MED JI Int. J. Psychiatr. Med. PY 2014 VL 48 IS 1 BP 33 EP 55 DI 10.2190/PM.48.1.d PG 23 WC Psychiatry SC Psychiatry GA AT3IZ UT WOS:000344830100004 PM 25354925 ER PT J AU Davidson, TM Yuen, EK Felton, JW McCauley, J Gros, KS Ruggiero, KJ AF Davidson, Tatiana M. Yuen, Erica K. Felton, Julia W. McCauley, Jenna Gros, Kirstin Stauffacher Ruggiero, Kenneth J. TI FEASIBILITY ASSESSMENT OF A BRIEF, WEB-BASED BEHAVIORAL ACTIVATION INTERVENTION FOR ADOLESCENTS WITH DEPRESSED MOOD SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE LA English DT Article DE behavioral activation; adolescents; depression; web-based intervention ID LONG-TERM OUTCOMES; DISORDER; TRIAL; ONSET AB Objective: Adolescent depression is a major public health concern. Efficacious interventions exist, but are underutilized. Novel approaches to improving access are therefore a top priority. Web-based approaches offer a viable treatment delivery solution; this approach may reach adolescents who might not otherwise receive formal treatment. Behavioral activation (BA) approaches have had success in treatment of depressive symptoms in youth. The purpose of this article is to: (1) describe the development process of a web-based, behavioral activation intervention for adolescents; (2) summarize the preliminary feasibility data; and (3) discuss the benefits and challenges associated with development and evaluation of adolescent self-help resources. Methods: The current study is part of a larger NIMH funded study focusing on the development and evaluation of Bounce Back Now (BBN), an evidence-informed, web resource for disaster-affected adolescents and their families. This study is specifically on the development of the BA component of the mood module of BBN, which was evaluated more extensively than other components. We present data from a formal usability evaluation conducted with 24 adolescents, and preliminary usage data collected from 2,000 disaster affected adolescents recruited from the tornado-affected coordinates in Alabama and Joplin, MO. Results: Preliminary data supported the feasibility of this approach: qualitative data with the clinic-based sample revealed favorable reactions to the intervention, and preliminary data from the large ongoing randomized controlled trial have indicated moderate levels of access. Conclusions: Brief, web-based approaches may offer a promising alternative to address access barriers for adolescents with depressed mood. C1 [Davidson, Tatiana M.; McCauley, Jenna; Gros, Kirstin Stauffacher; Ruggiero, Kenneth J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Yuen, Erica K.] Univ Tampa, Tampa, FL USA. [Felton, Julia W.] Univ Maryland, College Pk, MD 20742 USA. [Gros, Kirstin Stauffacher; Ruggiero, Kenneth J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Davidson, TM (reprint author), Med Univ S Carolina, Natl Crime Victims Res & Treatment Ctr, 67 President St IOP 2 South,MSC 861, Charleston, SC 29425 USA. EM davidst@musc.edu FU NIMH [R01 MH081056, R01 MH081056-03S2] FX This research is supported by NIMH Grant R01 MH081056 (PI: Ruggiero). Dr. Davidson is supported by NIMH Diversity Supplement Grant (R01 MH081056-03S2). Views expressed in this article do not necessarily reflect those of the VA or of the funding agencies acknowledged. NR 30 TC 3 Z9 3 U1 0 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2174 EI 1541-3527 J9 INT J PSYCHIAT MED JI Int. J. Psychiatr. Med. PY 2014 VL 48 IS 1 BP 69 EP 82 DI 10.2190/PM.48.1.f PG 14 WC Psychiatry SC Psychiatry GA AT3IZ UT WOS:000344830100006 PM 25354927 ER PT J AU Thomas, FP Goetz, LL Dixon, T Ho, C Holmes, SA Sandford, P Smith, S Ottomanelli, L AF Thomas, Florian P. Goetz, Lance L. Dixon, Thomas Ho, Chester Holmes, Sally Ann Sandford, Paul Smith, Sheila Ottomanelli, Lisa TI OPTIMIZING MEDICAL CARE TO FACILITATE AND SUSTAIN EMPLOYMENT AFTER SPINAL CORD INJURY SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Editorial Material ID TRAUMATIC BRAIN-INJURY; SUPPORTED EMPLOYMENT; PRESSURE ULCERS; CHRONIC PAIN; NEUROGENIC BOWEL; RISK-FACTORS; VETERANS; WORK; RETURN; MANAGEMENT C1 [Thomas, Florian P.] St Louis Univ, Dept Neurol & Psychiat, St Louis, MO 63103 USA. [Goetz, Lance L.] Hunter Holmes McGuire Dept Vet Affairs VA Med Ctr, Spinal Cord Injury Ctr, Richmond, VA USA. [Goetz, Lance L.] Virginia Commonwealth Univ, Dept Phys Med & Rehabil, Richmond, VA USA. [Dixon, Thomas] Louis Stokes Cleveland VA Med Ctr, Psychol Serv, Cleveland, OH USA. [Ho, Chester] Univ Calgary, Dept Clin Neurosci, Div Phys Med & Rehabil, Calgary, AB, Canada. [Holmes, Sally Ann] VA Med Ctr, Spinal Cord Injury Ctr, Houston, TX USA. [Holmes, Sally Ann] Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. [Sandford, Paul] Clement J Zablocki VA Med Ctr, Milwaukee, WI USA. [Sandford, Paul] Med Coll Wisconsin, Dept Phys Med & Rehabil, Milwaukee, WI 53226 USA. [Smith, Sheila] Louis Stokes VA Med Ctr, Spinal Cord Injury Ctr, Cleveland, OH USA. [Ottomanelli, Lisa] James A Haley Vet Affairs Hosp, Ctr Innovat Disabil & Rehabil Res, Tampa, FL USA. [Ottomanelli, Lisa] Univ S Florida, Dept Rehabil & Mental Hlth Counseling, Tampa, FL USA. RP Thomas, FP (reprint author), St Louis Univ, Dept Neurol & Psychiat, St Louis, MO 63103 USA. EM thomasfp@slu.edu NR 69 TC 1 Z9 1 U1 2 U2 5 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2014 VL 51 IS 6 BP XI EP XXI DI 10.1682/JRRD.2014.05.0119 PG 11 WC Rehabilitation SC Rehabilitation GA AT0OT UT WOS:000344635900003 PM 25479192 ER PT J AU Littman, AJ Boyko, EJ Thompson, ML Haselkorn, JK Sangeorzan, BJ Arterburn, DE AF Littman, Alyson J. Boyko, Edward J. Thompson, Mary Lou Haselkorn, Jodie K. Sangeorzan, Bruce J. Arterburn, David E. TI Physical activity barriers and enablers in older Veterans with lower-limb amputation SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE activity scale; amputee intervention; barriers; exercise; facilitators; lower-limb amputation; partial foot amputation; physical activity; trauma-related amputation; Veterans ID PATIENT-REPORTED OUTCOMES; INFORMATION-SYSTEM PROMIS; QUALITY-OF-LIFE; LOWER-EXTREMITY AMPUTEES; UNITED-STATES; ENERGY-EXPENDITURE; RECREATIONAL ACTIVITIES; ACTIVITY QUESTIONNAIRE; SEDENTARY BEHAVIOR; HEALTH-PROMOTION AB Little is known about the types of physical activities that older individuals with lower-limb loss perform, correlates of regular physical activity (PA), and barriers and facilitators to PA. We conducted an exploratory study in 158 older Veterans from the Pacific Northwest with a partial foot (35%), below-knee (39%), and above-knee (26%) amputation. Ninety-eight percent of survey respondents were male, on average 65 yr of age and 15 yr postamputation; 36% of amputations were trauma-related. The most commonly reported physical activities were walking/wheeling (65%), muscle strengthening (42%), exercise prescribed by a physical or occupational therapist (32%), and gardening (31%). Forty-three percent were classified as physically active based on weekly moderate-and vigorous-intensity PA. History of vigorous preamputation PA was positively associated with being active, while low wealth and watching 5 h/d or more of television/videos were inversely associated. While pain-and resource-related barriers to PA were most frequently reported, only knowledge-related and interest/motivation-related barriers were inversely associated with being active. Family support and financial assistance to join a gym were the most commonly reported factors that would facilitate PA. To increase PA in the older amputee population, interventions should address motivational issues, knowledge gaps, and television watching; reduce financial barriers to exercising; and consider involving family members. C1 [Littman, Alyson J.; Boyko, Edward J.; Thompson, Mary Lou] Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs VA Puget Sound Hlth Care Syst, Seattle, WA 98101 USA. [Littman, Alyson J.; Haselkorn, Jodie K.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Thompson, Mary Lou] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Haselkorn, Jodie K.] VA Puget Sound Hlth Care Syst, Multiple Sclerosis Ctr Excellence West, Seattle, WA USA. [Haselkorn, Jodie K.] Univ Washington, Dept Rehabil, Seattle, WA 98195 USA. [Sangeorzan, Bruce J.] VA Puget Sound Hlth Care Syst, Ctr Excellence Limb Loss Prevent & Prosthet Engn, Seattle, WA USA. [Sangeorzan, Bruce J.] Univ Washington, Med Ctr, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. [Sangeorzan, Bruce J.] Univ Washington, Harborview Med Ctr, Dept Orthopaed & Sports Med, Seattle, WA 98104 USA. [Arterburn, David E.] Grp Hlth Res Inst, Seattle, WA USA. RP Littman, AJ (reprint author), Seattle Epidemiol Res & Informat Ctr, VA Affairs Puget Sound Med Ctr, 1100 Olive Way,Metropolitan Pk West,Suite 1400, Seattle, WA 98101 USA. EM alyson.littman@va.gov FU VA Office of Research and Development Cooperative Studies Program; Seattle Epidemiologic Research and Information Center of the VA; VA Rehabilitation Research and Development Career Development Award [6982] FX This material was based on work supported in part by the VA Office of Research and Development Cooperative Studies Program. The Seattle Epidemiologic Research and Information Center of the VA provided support for this research. Dr. Littman's time was also supported by a VA Rehabilitation Research and Development Career Development Award (#6982). NR 53 TC 3 Z9 3 U1 3 U2 8 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2014 VL 51 IS 6 BP 895 EP 906 DI 10.1682/JRRD.2013.06.0152 PG 12 WC Rehabilitation SC Rehabilitation GA AT0OT UT WOS:000344635900008 PM 25356624 ER PT J AU Mahajan, HP Spaeth, DM Dicianno, BE Brown, K Cooper, RA AF Mahajan, Harshal P. Spaeth, Donald M. Dicianno, Brad E. Brown, Karl Cooper, Rory A. TI Preliminary evaluation of a variable compliance joystick for people with multiple sclerosis SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE fatigue; joystick; MS; multiple sclerosis; outcome measures; tremor filter; variable compliance joystick; virtual reality; wheelchair; wheelchair driving ID WHEELCHAIR DRIVING PERFORMANCE; TRAUMATIC BRAIN-INJURY; ASSISTIVE TECHNOLOGY; POWERED WHEELCHAIR; TREMOR; INDIVIDUALS; SIMULATOR; MOBILITY; FATIGUE; DISABILITIES AB Upper-limb fatigue is a common problem that may restrict people with multiple sclerosis (MS) from using their electric powered wheelchair effectively and for a long period of time. The objective of this research is to evaluate whether participants with MS can drive better with a variable compliance joystick (VCJ) and customizable algorithms than with a conventional wheelchair joystick. Eleven participants were randomly assigned to one of two groups. The groups used the VCJ in either compliant or noncompliant isometric mode and a standard algorithm, personally fitted algorithm, or personally fitted algorithm with fatigue adaptation running in the background in order to complete virtual wheelchair driving tasks. Participants with MS showed better driving performance metrics while using the customized algorithms than while using the standard algorithm with the VCJ. Fatigue adaptation algorithms are especially beneficial in improving overall task performance while using the VCJ in isometric mode. The VCJ, along with the personally fitted algorithms and fatigue adaptation algorithms, has the potential to be an effective input interface for wheelchairs. C1 [Mahajan, Harshal P.; Spaeth, Donald M.; Dicianno, Brad E.; Brown, Karl; Cooper, Rory A.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs VA Rehabil Res & Dev Ctr, Pittsburgh, PA 15206 USA. [Mahajan, Harshal P.; Cooper, Rory A.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Dicianno, Brad E.; Cooper, Rory A.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Dicianno, Brad E.; Cooper, Rory A.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. RP Dicianno, BE (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15206 USA. EM dicianno@pitt.edu FU Department of Veteran Affairs (VA) Research and Development Office [B3287R] FX This material was based on work supported by the Department of Veteran Affairs (VA) Research and Development Office (grant B3287R) and with the resources and facilities of HERL, VA Pittsburgh Healthcare System. NR 46 TC 3 Z9 3 U1 4 U2 6 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2014 VL 51 IS 6 BP 951 EP 961 DI 10.1682/JRRD.2013.01.0023 PG 11 WC Rehabilitation SC Rehabilitation GA AT0OT UT WOS:000344635900012 PM 25356558 ER PT S AU Pan, A Xu, L Petruccelli, JC Gupta, R Barbastathis, G AF Pan, Adam Xu, Ling Petruccelli, Jon C. Gupta, Rajiv Barbastathis, George BE DelRio, MS Chubar, O TI Contrast enhancement of propagation based X-ray phase contrast imaging SO ADVANCES IN COMPUTATIONAL METHODS FOR X-RAY OPTICS III SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Advances in Computational Methods for X-Ray Optics III CY AUG 18-21, 2014 CL San Diego, CA SP SPIE DE Phase retrieval; transport of intensity; X-ray imaging ID COMPUTED-TOMOGRAPHY; INTENSITY EQUATION; RETRIEVAL; ALGORITHMS; TRANSPORT; RECONSTRUCTION; NOISE AB We demonstrate a quantitative X-ray phase contrast imaging (XPCI) technique derived from propagation dependent phase change. We assume that the absorption and phase components are correlated and solve the Transport of Intensity Equation (TIE). The experimental setup is simple compared to other XPCI techniques; the only requirements are a micro-focus X-ray source with sufficient temporal coherence and an X-ray detector of sufficient spatial resolution. This method was demonstrated in three scenarios, the first of which entails identification of an index-matched sphere. A rubber and nylon sphere were immersed in water and imaged. While the rubber sphere could be plainly seen on a radiograph, the nylon sphere was only visible in the phase reconstruction. Next, the technique was applied to differentiating liquid samples. In this scenario, three liquid samples (acetone, water, and hydrogen peroxide) were analyzed using both conventional computed tomography (CT) and phase contrast CT. While conventional CT was capable of differentiating between acetone and the other two liquids, it failed to distinguish between water and hydrogen peroxide; only phase CT was capable of differentiating all three samples. Finally, the technique was applied to CT imaging of a human artery specimen with extensive atherosclerotic plaque. This scenario demonstrated the increased sensitivity to soft tissue compared to conventional CT; it also uncovered some drawbacks of the method, which will be the target of future work. In all cases, the signal-to-noise ratio of phase contrast was greatly enhanced relative to conventional attenuation-based imaging. C1 [Pan, Adam; Xu, Ling] MIT, Dept Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Petruccelli, Jon C.] SUNY Albany, Dept Phys, Albany, NY 12222 USA. [Gupta, Rajiv] Massachusetts Gen Hosp, Dept Mech Engn, Boston, MA 02215 USA. [Barbastathis, George] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Barbastathis, George] MIT Allance Res & Technol SMART Ctr, Singapore 138602, Singapore. [Barbastathis, George] Shanghai Jiao Tong Univ, Univ Michigan Joint Inst, Shanghai 200240, Peoples R China. RP Pan, A (reprint author), MIT, Dept Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM apan@mit.edu FU Department of Homeland Security,Science and Technology Directorate [HSHQDC-11-C-00083] FX We are grateful to Justin Lee,Lei Tian,Bipin Singh,and DavidJ.Brady for helpful discussions.This work was supported by the Department of Homeland Security,Science and Technology Directorate through contract HSHQDC-11-C-00083. NR 27 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 978-1-62841-236-9 J9 PROC SPIE PY 2014 VL 9209 AR UNSP 92090R DI 10.1117/12.2060605 PG 10 WC Engineering, Electrical & Electronic; Optics SC Engineering; Optics GA BB5PE UT WOS:000344012500022 ER PT J AU Azim, HA Partridge, AH AF Azim, Hatem A., Jr. Partridge, Ann H. TI Biology of breast cancer in young women SO BREAST CANCER RESEARCH LA English DT Review ID PATHOLOGICAL FEATURES; REPRODUCTIVE FACTORS; MUTATIONAL PROCESSES; LESS-THAN-35 YEARS; MAMMARY-GLAND; PREGNANCY; AGE; PROGNOSIS; SURVIVAL; RISK AB Breast cancer arising at a young age is relatively uncommon, particularly in the developed world. Several studies have demonstrated that younger patients often experience a more aggressive disease course and have poorer outcome compared to older women. Expression of key biomarkers, including endocrine receptors, HER2 and proliferation markers, appears to be different in younger patients and young women are more likely to harbor a genetic predisposition. Despite these differences, little research to date has focused on the biology of these tumors to refine prognosis, and potentially direct treatment strategies, which remain similar to those offered to older patients. Accumulating evidence suggests the differences in breast stroma in younger patients and changes that occur with pregnancy and breastfeeding likely contribute to the different biology of these tumors. Reproductive behaviors appear to impact the biology of tumors developing later in life. In addition, tumors arising during or shortly following pregnancy appear to exhibit unique biological features. In this review, we discuss our emerging understanding of the biology of breast cancer arising at a young age at both the pathologic and the genomic level. We elucidate the potential role of genomic signatures, the impact of pregnancy and breastfeeding on breast cancer biology, and how even current knowledge might advance the clinical management of young breast cancer patients. C1 [Azim, Hatem A., Jr.] Univ Libre Bruxelles, Inst Jules Bordet, Dept Med, BrEAST Data Ctr, B-1000 Brussels, Belgium. [Partridge, Ann H.] Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Ctr, Boston, MA 02115 USA. RP Azim, HA (reprint author), Univ Libre Bruxelles, Inst Jules Bordet, Dept Med, BrEAST Data Ctr, B-1000 Brussels, Belgium. EM hatem.azim@bordet.be FU Amgen FX HAA received honoraria for consultancy/advisory board roles from Glaxo-Smith Kline, Novartis, Nanostring and Celgene, and received research support from Amgen. AHP declares that she has no competing interests. NR 62 TC 28 Z9 28 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2014 VL 16 IS 4 AR 427 DI 10.1186/s13058-014-0427-5 PG 9 WC Oncology SC Oncology GA AS5KQ UT WOS:000344310300030 PM 25436920 ER PT J AU Marshall, GA Zoller, AS Kelly, KE Amariglio, RE Locascio, JJ Johnson, KA Sperling, RA Rentz, DM AF Marshall, Gad A. Zoller, Amy S. Kelly, Kathleen E. Amariglio, Rebecca E. Locascio, Joseph J. Johnson, Keith A. Sperling, Reisa A. Rentz, Dorene M. CA Alzheimer's Dis Neuroimaging Initi TI Everyday Cognition Scale Items that Best Discriminate Between and Predict Progression From Clinically Normal to Mild Cognitive Impairment SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Activities of daily living; Alzheimer's disease; clinical assessment; daily functioning; clinically normal elderly; mild cognitive impairment ID ALZHEIMERS ASSOCIATION WORKGROUPS; INSTRUMENTAL ACTIVITIES; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; DISEASE SPECTRUM; DEMENTIA; RECOMMENDATIONS; COMMUNITY; DECLINE; SELF AB Background: Impairment in instrumental activities of daily living (IADL) starts as individuals with amnestic mild cognitive impairment (MCI) transition to Alzheimer's disease (AD) dementia. However, most IADL scales have not shown IADL alterations in clinically normal (CN) elderly. The objective of this study was to determine which of the IADL-related Everyday Cognition (ECog) scale items are most sensitive for detection of early functional changes. Methods: We assessed 290 CN and 495 MCI participants from the Alzheimer's Disease Neuroimaging Initiative. We performed logistic regression analyses predicting the probability of CN vs. MCI diagnosis using only the 17 participant-based and 17 informant-based ECog items related to IADL. We then performed Cox regression analyses to predict progression from CN to MCI. All analyses were adjusted for demographic characteristics. Results: We found that worse performance on "remembering a few shopping items" (participant and informant-based p<0.0001), "remembering appointments" (participant and informant-based p<0.0001), "developing a schedule in advance of anticipated events" (participant-based p=0.007), "balancing checkbook" (participant-based p=0.02), and "keeping mail and papers organized" (informant-based p=0.002) best discriminated MCI from CN. We found that worse performance on "keeping mail and papers organized" (participant-based Hazard Ratio (HR)=2.27, p=0.07) marginally predicted greater hazard of progressing from CN to MCI. Conclusions: Our results indicate that a few simple questions targeting early functional changes, addressed either to the individual or informant, can effectively distinguish between CN elderly and individuals with MCI. Additionally, one of the above questions related to organization suggested which CN individuals are likely to progress to MCI. C1 [Marshall, Gad A.; Amariglio, Rebecca E.; Johnson, Keith A.; Sperling, Reisa A.; Rentz, Dorene M.] Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Marshall, Gad A.; Amariglio, Rebecca E.; Johnson, Keith A.; Sperling, Reisa A.; Rentz, Dorene M.] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Sch Med, Boston, MA 02115 USA. [Marshall, Gad A.; Zoller, Amy S.; Kelly, Kathleen E.; Amariglio, Rebecca E.; Locascio, Joseph J.; Johnson, Keith A.; Sperling, Reisa A.; Rentz, Dorene M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02115 USA. [Marshall, Gad A.; Amariglio, Rebecca E.; Locascio, Joseph J.; Sperling, Reisa A.; Rentz, Dorene M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. [Zoller, Amy S.; Kelly, Kathleen E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. [Johnson, Keith A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. RP Marshall, GA (reprint author), Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, 221 Longwood Ave,BL-104H, Boston, MA 02115 USA. EM gamarshall@partners.org FU ADNI [U01 AG024904]; DOD ADNI [W81XWH-12-2-0012]; Harvard Aging Brain Study [P01 AGO36694]; Massachusetts Alzheimer's Disease Research Center [P50 AG005134]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd; Genentech, Inc.; GE Healthcare; Innogenetics, N.V; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; Takeda Pharmaceutical Company; Canadian Institutes of Health Research; Northern California Institute for Research and Education; [R01 AG027435]; [K23 AG033634]; [K24 AG035007] FX This study was supported by ADNI (U01 AG024904), DOD ADNI (W81XWH-12-2-0012), R01 AG027435, K23 AG033634, K24 AG035007, the Harvard Aging Brain Study (P01 AGO36694), and the Massachusetts Alzheimer's Disease Research Center (P50 AG005134). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. NR 30 TC 8 Z9 8 U1 3 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 EI 1875-5828 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PY 2014 VL 11 IS 9 BP 853 EP 861 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AS1PH UT WOS:000344052100004 PM 25274110 ER PT J AU Gliklich, RE Leavy, MB Karl, J Campion, DM Levy, D Berliner, E AF Gliklich, Richard E. Leavy, Michelle B. Karl, Jannette Campion, Daniel M. Levy, Daniel Berliner, Elise TI A framework for creating standardized outcome measures for patient registries SO JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH LA English DT Article DE comparative effectiveness research; conceptual model; outcome measure; outcome measurement; patient outcomes; patient registry AB Aim: Our objectives were to create a conceptual framework for development of standard outcome measures and to design and pilot test a tool for displaying outcome measures. Materials & methods: Information on outcome measures used in registries was gathered through stakeholder discussions, which informed the development of the outcome measurement framework and the related tool. Results: The outcome measurement framework is a conceptual model for how information relevant to evaluating patient outcomes may be defined and collected in a standard way for a broad range of health areas. The related tool facilitates collecting, displaying and searching for information on outcome measures. Conclusion: The model developed through this process offers a framework that can be used to define outcome measures in a standard way across medical conditions. C1 [Gliklich, Richard E.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Leavy, Michelle B.; Karl, Jannette] Quintiles, Cambridge, MA 02139 USA. [Campion, Daniel M.] Quintiles, Rockville, MD 20852 USA. [Levy, Daniel] Amazing Charts, Boston, MA 02199 USA. [Berliner, Elise] Agcy Healthcare Res & Qual, Rockville, MD 20850 USA. RP Leavy, MB (reprint author), Quintiles, 201 Broadway, Cambridge, MA 02139 USA. EM michelle.leavy@quintiles.com FU Agency for Healthcare Research and Quality under Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program [HHSA29020050035I TO7] FX The project described in this article was funded by the Agency for Healthcare Research and Quality under the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program (contract number HHSA29020050035I TO7). 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 17 TC 0 Z9 0 U1 0 U2 3 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 2042-6305 EI 2042-6313 J9 J COMP EFFECT RES JI J. Comp. Eff. Res. PY 2014 VL 3 IS 5 BP 473 EP 480 DI 10.2217/CER.14.38 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AS6QI UT WOS:000344387200006 PM 25350799 ER PT J AU Levine, BS Rodriguez, M Felsenfeld, AJ AF Levine, Barton S. Rodriguez, Mariano Felsenfeld, Arnold J. TI Serum calcium and bone: effect of PTH, phosphate, vitamin D and uremia SO NEFROLOGIA LA English DT Review DE Bone; Calcium; Parathyroid hormone; Phosphate; Uremia; Vitamin D ID CHRONIC KIDNEY-DISEASE; PARATHYROID-HORMONE; D INTOXICATION; RENAL-FAILURE; HEMODIALYSIS-PATIENTS; SKELETAL RESISTANCE; DIETARY PHOSPHORUS; CALCEMIC RESPONSE; SECONDARY HYPERPARATHYROIDISM; D DEFICIENCY AB Hyperparathyroidism develops in chronic kidney disease (CKD). A decreased calcemic response to parathyroid hormone (PTH) contributes to the development of hyperparathyroidism and is presumed due to reduced calcium efflux from bone. Contributing factors to the decreased calcemic response to PTH in CKD include: 1) hyperphosphatemia; 2) decreased serum calcitriol; 3) downregulation of the PTH1 receptor; 4) large, truncated amino-terminal PTH fragments acting at the carboxy-PTH receptor; and 5) uremic toxins. Also, prolonged high dose calcitriol administration may decrease the exchangeable pool of bone calcium independent of PTH. The goal of the review is to provide a better understanding of how the above cited factors affect calcium efflux from bone in CKD. In conclusion, much remains to be learned about the role of bone in the regulation of serum calcium. C1 [Levine, Barton S.; Felsenfeld, Arnold J.] Univ Calif Los Angeles, Dept Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. [Levine, Barton S.; Felsenfeld, Arnold J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rodriguez, Mariano] Hosp Univ Reina Sofia, IMIBIC, Dept Nephrol, Red Ren, Cordoba, Spain. RP Felsenfeld, AJ (reprint author), Univ Calif Los Angeles, Dept Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. EM Arnold.Felsenfeld@va.gov FU Instituto Carlos III [FIS 07/0287, FIS 07/0315, 010/1311]; Consejeria de Salud [JA 0127/2008]; UE [FP7-241544]; Consejeria de Innovacion, Ciencia y Empresa of Junta de Andalucia [CTS-5205, CTS-170] FX M.R. has received grant support from the Instituto Carlos III (FIS 07/0287, FIS 07/0315, 010/1311), Consejeria de Salud (JA 0127/2008), a UE Grant from Framework Programme 7 Syskid (FP7-241544), and Consejeria de Innovacion, Ciencia y Empresa (CTS-5205 and CTS-170) of Junta de Andalucia. NR 88 TC 3 Z9 3 U1 2 U2 7 PU SOC ESPANOLA NEFROLOGIA DR RAFAEL MATESANZ PI MADRID PA HOSPITAL RAMON Y CAJAL CTR DE COLMENAR, KM 9,100, 28034 MADRID, SPAIN SN 0211-6995 EI 1989-2284 J9 NEFROLOGIA JI Nefrologia PY 2014 VL 34 IS 5 BP 658 EP 669 DI 10.3265/Nefrologia.pre2014.Jun.12379 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA AS1FR UT WOS:000344025900017 PM 25259820 ER PT J AU Kasimova, KR Sadasivam, M Landi, G Sarna, T Hamblin, MR AF Kasimova, Kamola R. Sadasivam, Magesh Landi, Giacomo Sarna, Tadeusz Hamblin, Michael R. TI Potentiation of photoinactivation of Gram-positive and Gram-negative bacteria mediated by six phenothiazinium dyes by addition of azide ion SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES LA English DT Article ID ANTIMICROBIAL PHOTODYNAMIC THERAPY; METHYLENE-BLUE DERIVATIVES; SINGLET OXYGEN; PHOTOBACTERICIDAL ACTIVITY; ESCHERICHIA-COLI; OUTER-MEMBRANE; SODIUM-AZIDE; IN-VITRO; INACTIVATION; REDUCTION AB Antimicrobial photodynamic inactivation (APDI) using phenothiazinium dyes is mediated by reactive oxygen species consisting of a combination of singlet oxygen (quenched by azide), hydroxyl radicals and other reactive oxygen species. We recently showed that addition of sodium azide paradoxically potentiated APDI of Gram-positive and Gram-negative bacteria using methylene blue as the photosensitizer, and this was due to electron transfer to the dye triplet state from azide anion, producing azidyl radical. Here we compare this effect using six different homologous phenothiazinium dyes: methylene blue, toluidine blue O, new methylene blue, dimethylmethylene blue, azure A, and azure B. We found both significant potentiation (up to 2 logs) and also significant inhibition (> 3 logs) of killing by adding 10 mM azide depending on Gram classification, washing the dye from the cells, and dye structure. Killing of E. coli was potentiated with all 6 dyes after a wash, while S. aureus killing was only potentiated by MB and TBO with a wash and DMMB with no wash. More lipophilic dyes (higher log P value, such as DMMB) were more likely to show potentiation. We conclude that the Type I photochemical mechanism (potentiation with azide) likely depends on the microenvironment, i. e. higher binding of dye to bacteria. Bacterial dye-binding is thought to be higher with Gram-negative compared to Gram-positive bacteria, when unbound dye has been washed away, and with more lipophilic dyes. C1 [Kasimova, Kamola R.; Sadasivam, Magesh; Landi, Giacomo; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Kasimova, Kamola R.] Republ Res Ctr Emergency Med, Tashkent, Uzbekistan. [Kasimova, Kamola R.] Tashkent Med Acad, Tashkent, Uzbekistan. [Landi, Giacomo; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Landi, Giacomo] Univ Siena, Dept Mol Med, I-53100 Siena, Italy. [Sarna, Tadeusz] Jagiellonian Univ, Fac Biochem Biophys & Biotechnol, Krakow, Poland. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU US NIH [R01AI050875] FX This work was supported by US NIH grant R01AI050875. NR 41 TC 11 Z9 11 U1 3 U2 13 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1474-905X EI 1474-9092 J9 PHOTOCH PHOTOBIO SCI JI Photochem. Photobiol. Sci. PY 2014 VL 13 IS 11 BP 1541 EP 1548 DI 10.1039/c4pp00021h PG 8 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA AS0TL UT WOS:000343991400005 PM 25177833 ER PT J AU Storey, RF James, SK Siegbahn, A Varenhorst, C Held, C Ycas, J Husted, SE Cannon, CP Becker, RC Steg, PG Asenblad, N Wallentin, L AF Storey, Robert F. James, Stefan K. Siegbahn, Agneta Varenhorst, Christoph Held, Claes Ycas, Joseph Husted, Steen E. Cannon, Christopher P. Becker, Richard C. Steg, Ph Gabriel Asenblad, Nils Wallentin, Lars TI Lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the PLATO study SO PLATELETS LA English DT Article DE Clopidogrel; coronary artery disease; platelet aggregation inhibitors; pneumonia; sepsis; ticagrelor ID ACUTE CORONARY SYNDROMES; PLATELET P2Y(12) RECEPTOR; ARTERY-BYPASS SURGERY; INFLAMMATORY MARKERS; ANTIPLATELET DRUGS; CLINICAL-OUTCOMES; REVASCULARIZATION; INHIBITION; ADENOSINE; ASPIRIN AB In the PLATelet inhibition and patient Outcomes (PLATO) study of patients with acute coronary syndromes, ticagrelor reduced mortality compared to clopidogrel but the mechanisms for this mortality reduction remain uncertain. We analysed adverse events (AEs) consistent with either pulmonary infection or sepsis, and subsequent mortality, in 18,421 PLATO patients treated with ticagrelor or clopidogrel. AEs occurring within 7 days of last dose of study medication were defined as "on-treatment". Serial measurements of blood leukocyte counts, C-reactive protein and interleukin-6 were performed. Fewer on-treatment pulmonary AEs occurred in the ticagrelor compared to the clopidogrel group (275 vs. 331 respectively; p = 0.019), with fewer deaths following these AEs (33 vs. 71; p < 0.001), particularly in those who remained on study medication three days after AE onset (10 vs. 43; p = 0.001). There were fewer deaths attributed to sepsis in the ticagrelor group (7 vs. 23; p = 0.003). Leukocyte counts were lower in the clopidogrel group during treatment (p < 0.0001 at 1, 3 and 6 months) but not at 1 month post-discontinuation. C-reactive protein increased more at discharge in the ticagrelor group (28.0 +/- 38.0 vs. 26.1 +/- 36.6 mg/l; p < 0.001) and interleukin-6 remained higher during the first month of treatment with ticagrelor. We conclude that the mortality risk following pulmonary AEs and sepsis in acute coronary syndrome patients appears to be lower during ticagrelor compared to clopidogrel therapy. Further work should assess whether ticagrelor and clopidogrel have differential effects on immune signalling. C1 [Storey, Robert F.] Univ Sheffield, Dept Cardiovasc Sci, Sheffield S10 2RX, S Yorkshire, England. [James, Stefan K.; Siegbahn, Agneta; Varenhorst, Christoph; Held, Claes; Asenblad, Nils; Wallentin, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [James, Stefan K.; Siegbahn, Agneta; Varenhorst, Christoph; Held, Claes; Asenblad, Nils; Wallentin, Lars] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden. [Ycas, Joseph] AstraZeneca, Wilmington, DE USA. [Husted, Steen E.] Arhus Univ Hosp, Aarhus, Denmark. [Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Becker, Richard C.] Univ Cincinnati, Coll Med, Div Cardiovasc Hlth & Dis, Cincinnati, OH 45221 USA. [Becker, Richard C.] Univ Cincinnati, Coll Med, Heart Lung & Vasc Inst, Cincinnati, OH 45221 USA. [Steg, Ph Gabriel] Univ Paris Diderot, Hop Bichat, AP HP, Paris, France. [Steg, Ph Gabriel] Univ Paris Diderot, Dept Hosp Univ FIRE, Paris, France. RP Storey, RF (reprint author), Univ Sheffield, Dept Cardiovasc Sci, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England. EM r.f.storey@sheffield.ac.uk OI Varenhorst, Christoph/0000-0002-8378-3869; Held, Claes/0000-0001-9402-7404 FU AstraZeneca; Eli Lilly/Daiichi Sankyo; Merck; Accumetrics; Novartis; Roche; Sanofi Aventis; Regeneron; Eli Lilly; Bristol-Myers Squibb; Boehringer-Ingelheim; GlaxoSmithKline; Pfizer; Sanofi-Aventis; Essentialis; Sanofi; Takeda; NYU School of Medicine; Servier; Ablynx; Amarin; Amgen; Astellas; Bayer; BMS; Daiichi/sankyo; Eisai; GSK; Lilly; Medtronic; MSD; Otsuka; Medicines Company, and Vivus; Merck/Schering-Plough; Boehringer Ingelheim; Bristol-Myers Squibb/Pfizer; Schering-Plough FX This work was supported by AstraZeneca. R. F. Storey reports receiving research grants from AstraZeneca, Eli Lilly/Daiichi Sankyo, and Merck; research support from Accumetrics; honoraria from AstraZeneca, Eli Lilly/Daiichi Sankyo, Merck, Novartis, Iroko, Sanofi-Aventis/BMS, Accumetrics, and Medscape; consultancy fees from AstraZeneca, Merck, Novartis, Accumetrics, Roche, Sanofi Aventis, and Regeneron.; S. K. James reports institutional research grant and honoraria from AstraZeneca, Eli Lilly, Merck and Bristol-Myers Squibb and being an advisory board member for AstraZeneca, Eli Lilly and Merck. Honoraria from The Medicines Company.; A. Siegbahn reports Institutional grants from Boehringer-Ingelheim and Astrazeneca; and honoraria from Boehringer-Ingelheim.; C. Held reports institutional research grants from AstraZeneca, Merck, GlaxoSmithKline, Roche and Bristol-Myers Squibb and being an advisory board member for AstraZeneca, Honoraria from AstraZeneca.; S. Husted reports being an advisory board member for AstraZeneca, Bristol-Myers Squibb, Pfizer, and Bayer; research support from GlaxoSmithKline, Pfizer, and Sanofi-Aventis.; C. P. Cannon reports receiving research grants/support from Accumetrics, AstraZeneca, Essentialis, GlaxoSmithKline, Merck, Regeneron, Sanofi, and Takeda; being on advisory boards for Alnylam, Bristol-Myers Squibb, CSL Behring, and Pfizer (funds donated to charity); and a Clinical Advisor with equity in Automedics Medical Systems.; P. G. Steg has received research grants from NYU School of Medicine, Sanofi, Servier; consultancy fees/honoraria from Ablynx, Amarin, Amgen, Astellas, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS, Daiichi/sankyo, Eisai, GSK, Lilly, Medtronic, MSD, Novartis, Otsuka, Pfizer, Roche, Sanofi, Servier, The Medicines Company, and Vivus; and has equity ownership in Aterovax.; L. Wallentin reports receiving research grants from AstraZeneca, Merck/Schering-Plough, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, GlaxoSmithKline; being a consultant for Merck/Schering-Plough, Regado Biosciences, Evolva, Portola, C. S. L. Behring, Athera Biotechnologies, Boehringer Ingelheim, AstraZeneca, GlaxoSmithKline, and Bristol-Myers Squibb/Pfizer; lecture fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, GlaxoSmithKline, Schering-Plough; and honoraria from Boehringer Ingelheim, AstraZeneca, Bristol-Myers Squibb/Pfizer, GlaxoSmithKline, and Schering-Plough/Merck. NR 33 TC 15 Z9 18 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0953-7104 EI 1369-1635 J9 PLATELETS JI Platelets PY 2014 VL 25 IS 7 BP 517 EP 525 DI 10.3109/09537104.2013.842965 PG 9 WC Cell Biology; Hematology SC Cell Biology; Hematology GA AS4ER UT WOS:000344226500007 PM 24127651 ER PT J AU Mulligan, EA Wachen, JS Naik, AD Gosian, J Moye, J AF Mulligan, Elizabeth A. Wachen, Jennifer Schuster Naik, Aanand D. Gosian, Jeffrey Moye, Jennifer TI Cancer as a Criterion A Traumatic Stressor for Veterans: Prevalence and Correlates SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE cancer; PTSD; Criterion A ID BONE-MARROW-TRANSPLANTATION; BREAST-CANCER; POSTTRAUMATIC-STRESS; DISORDER SYMPTOMATOLOGY; SYMPTOMS; WOMEN; SURVIVORS; DISTRESS; ANXIETY; CHEMOTHERAPY AB The diagnosis of cancer is an uncontrollable stressor posing the threat of death and disfigurement, often followed by repeated exposure to aversive reminders in the form of noxious treatments, persisting side effects, reengagement at times of surveillance, and the threat of recurrence. The phenomenon of cancer as a traumatic stressor is explored in this study, with a focus on the prevalence and correlates of posttraumatic stress disorder (PTSD) Criterion A in a sample of 170 mostly male adults who received health care at VA Medical Centers in Boston or Houston. Participants were interviewed 6 months after diagnosis with head and neck, gastro-esophageal, or colorectal cancers. Approximately half-42.9% to 65.9% depending on cut-score used-perceived cancer to be a traumatic stressor involving actual/threatened death or injury or threat to physical integrity as well as fear, helplessness, or horror. Younger veterans and those with current combat PTSD symptoms were more likely to perceive cancer as a traumatic stressor, as were those who perceived their prognosis as uncertain; 12% had PTSD symptoms above a PCLC cut score of 50, which is similar to incidence rates of PTSD associated with other traumatic stressors. Cancer, therefore, appears to be a serious and for some, traumatic stressor, suggesting the importance of screening for cancer related PTSD in cancer survivors, particularly those most at risk. C1 [Mulligan, Elizabeth A.; Wachen, Jennifer Schuster; Gosian, Jeffrey; Moye, Jennifer] VA Boston Healthcare Syst, Brockton, MA 02301 USA. [Mulligan, Elizabeth A.; Moye, Jennifer] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Wachen, Jennifer Schuster] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Naik, Aanand D.] Michael E DeBakey VAMC, Hlth Serv Res & Dev, Houston, TX USA. [Naik, Aanand D.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Moye, J (reprint author), VA Boston Healthcare Syst, Brockton Div, 940 Belmont St, Brockton, MA 02301 USA. EM jennifer.moye@va.gov RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X FU RRD VA [I01 RX000104] NR 47 TC 2 Z9 2 U1 6 U2 7 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PY 2014 VL 6 SU 1 SI SI BP S73 EP S81 DI 10.1037/a0033721 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AS7ZU UT WOS:000344471200009 PM 25741406 ER PT J AU Wachen, JS Jimenez, S Smith, K Resick, PA AF Wachen, Jennifer Schuster Jimenez, Sherlyn Smith, Kamala Resick, Patricia A. TI Long-Term Functional Outcomes of Women Receiving Cognitive Processing Therapy and Prolonged Exposure SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE posttraumatic stress disorder; psychosocial functioning; cognitive processing therapy; prolonged exposure; randomized controlled trial ID POSTTRAUMATIC-STRESS-DISORDER; QUALITY-OF-LIFE; MALE VIETNAM VETERANS; SOCIAL-ADJUSTMENT; ANXIETY DISORDERS; RANDOMIZED-TRIAL; ASSAULT VICTIMS; SEXUAL ASSAULT; SELF-REPORT; PTSD AB The current study sought to determine whether trauma-focused treatments for posttraumatic stress disorder (PTSD) improve psychosocial functioning outcomes, and whether treatment gains are maintained over a long-term follow-up (LTFU) period (5-10 years). The relationship between symptoms of PTSD and depression and psychosocial functioning also were explored. A sample of 154 female rape victims who received cognitive processing therapy (CPT) or prolonged exposure therapy (PE) were assessed at pretreatment, posttreatment, 9 months, and 5-10 years following treatment. Hierarchical linear modeling demonstrated significant improvements in overall functioning, social/leisure adjustment, family unit adjustment, and economic adjustment in both treatment conditions, with gains maintained over the LTFU. Lower household income at baseline was associated significantly with poorer overall functioning, social/leisure adjustment, and economic adjustment over time. Structural equation modeling revealed that poorer overall functioning at posttreatment was associated significantly with higher levels of depressive symptoms at 9 months, whereas higher levels of depressive symptoms at 9 months were associated significantly with poorer levels of overall functioning at LTFU. Findings suggest that both cognitive and exposure-based treatments for PTSD have the potential to impact functioning outcomes over a long period of time. C1 [Wachen, Jennifer Schuster; Jimenez, Sherlyn; Smith, Kamala; Resick, Patricia A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Wachen, Jennifer Schuster; Jimenez, Sherlyn; Resick, Patricia A.] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. RP Wachen, JS (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, 150 South Huntington Ave 116B-3, Boston, MA 02130 USA. EM jennifer.wachen@va.gov NR 48 TC 0 Z9 0 U1 1 U2 8 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PY 2014 VL 6 SU 1 SI SI BP S58 EP S65 DI 10.1037/a0035741 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AS7ZU UT WOS:000344471200007 ER PT J AU Roffman, JL Witte, JM Tanner, AS Ghaznavi, S Abernethy, RS Crain, LD Giulino, PU Lable, I Levy, RA Dougherty, DD Evans, KC Fava, M AF Roffman, Joshua L. Witte, Janet M. Tanner, Alexandra S. Ghaznavi, Sharmin Abernethy, Robert S. Crain, Laura D. Giulino, Patricia U. Lable, Ira Levy, Raymond A. Dougherty, Darin D. Evans, Karleyton C. Fava, Maurizio TI Neural Predictors of Successful Brief Psychodynamic Psychotherapy for Persistent Depression SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE Psychotherapy; Depression; Positron emission tomography ID MAJOR DEPRESSION; METAANALYSIS; THERAPY; INSULA AB Background: Psychodynamic psychotherapy has been used to treat depression for more than a century. However, not all patients respond equally well, and there are few reliable predictors of treatment outcome. Methods: We used resting F-18-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) scans immediately before and after a structured, open trial of brief psychodynamic psychotherapy (n = 16) in conjunction with therapy process ratings and clinical outcome measures to identify neural correlates of treatment response. Results: Pretreatment glucose metabolism within the right posterior insula correlated with depression severity. Reductions in depression scores correlated with a pre- to posttreatment reduction in right insular metabolism, which in turn correlated with higher objective measures of patient insight obtained from videotaped therapy sessions. Pretreatment metabolism in the right precuneus was significantly higher in patients who completed treatment and correlated with psychological mindedness. Conclusions: Resting brain metabolism predicted both clinical course and relevant psychotherapeutic process during short-term psychodynamic psychotherapy for depression. (C) 2014 S. Karger AG, Basel C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Roffman, JL (reprint author), Massachusetts Gen Hosp, Room 2606,149 13th St, Charlestown, MA 02129 USA. EM jroffman@partners.org FU Hope for Depression Research Foundation; Massachusetts General Hospital (MGH) Endowment for the Advancement for Psychotherapy; MGH Depression Clinical and Research Program FX This work was supported by a grant from the Hope for Depression Research Foundation (to J.L.R. and J.M.W.) as well as by the Massachusetts General Hospital (MGH) Endowment for the Advancement for Psychotherapy and the MGH Depression Clinical and Research Program. NR 25 TC 9 Z9 9 U1 0 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 EI 1423-0348 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2014 VL 83 IS 6 BP 364 EP 370 DI 10.1159/000364906 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA AS7IH UT WOS:000344429600005 PM 25323387 ER PT S AU Allum, WH Bonavina, L Cassivi, SD Cuesta, MA Dong, ZM Felix, VN Figueredo, E Gatenby, PAC Haverkamp, L Ibraev, MA Krasna, MJ Lambert, R Langer, R Lewis, MPN Nason, KS Parry, K Preston, SR Ruurda, JP Schaheen, LW Tatum, RP Turkin, IN van der Horst, S van der Peet, DL van der Sluis, PC van Hillegersberg, R Wormald, JCR Wu, PC AF Allum, William H. Bonavina, Luigi Cassivi, Stephen D. Cuesta, Miguel A. Dong, Zhao Ming Nilton Felix, Valter Figueredo, Edgar Gatenby, Piers A. C. Haverkamp, Leonie Ibraev, Maksat A. Krasna, Mark J. Lambert, Rene Langer, Rupert Lewis, Michael P. N. Nason, Katie S. Parry, Kevin Preston, Shaun R. Ruurda, Jelle P. Schaheen, Lara W. Tatum, Roger P. Turkin, Igor N. van der Horst, Sylvia van der Peet, Donald L. van der Sluis, Peter C. van Hillegersberg, Richard Wormald, Justin C. R. Wu, Peter C. BE Giuli, R Umar, A TI Surgical treatments for esophageal cancers SO 12TH OESO WORLD CONFERENCE: CANCERS OF THE ESOPHAGUS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 12th OESO World Conference - Cancers of the Esophagus CY AUG, 2013 CL UNESCO, Paris, FRANCE SP World Hlth Org, Int Agcy Res Canc, Natl Canc Inst HO UNESCO DE esophageal resection; Nissen fundoplication; esophagogastrostomy; esophagectomy; chemoradiotherapy; OESO ID QUALITY-OF-LIFE; CIRCUMFERENTIAL RESECTION MARGIN; RANDOMIZED CONTROLLED-TRIAL; SQUAMOUS-CELL CARCINOMA; CHYLOTHORAX COMPLICATING ESOPHAGECTOMY; LONG-TERM SURVIVAL; EXTENDED TRANSTHORACIC RESECTION; MINIMALLY INVASIVE ESOPHAGECTOMY; LAPAROSCOPIC ANTIREFLUX SURGERY; BARRETTS-ESOPHAGUS AB The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the role of the nurse in preparation of esophageal resection ( ER); the management of patients who develop high-grade dysplasia after having undergone Nissen fundoplication; the trajectory of care for the patient with esophageal cancer; the influence of the site of tumor in the choice of treatment; the best location for esophagogastrostomy; management of chylous leak after esophagectomy; the optimal approach to manage thoracic esophageal leak after esophagectomy; the choice for operational approach in surgery of cardioesophageal crossing; the advantages of robot esophagectomy; the place of open esophagectomy; the advantages of esophagectomy compared to definitive chemoradiotherapy; the pathologist report in the resected specimen; the best way to manage patients with unsuspected positive microscopic margin after ER; enhanced recovery after surgery for ER: expedited care protocols;and long-term quality of life in patients following esophagectomy. C1 [Allum, William H.; Gatenby, Piers A. C.] UCL, Div Surg & Intervent Sci, London, England. [Bonavina, Luigi] Univ Milan, Sch Med, Div Gen Surg, Dept Biomed Sci Hlth, Milan, Italy. [Cassivi, Stephen D.] Mayo Clin, Dept Surg, Rochester, MN USA. [Cuesta, Miguel A.; van der Peet, Donald L.] Vrije Univ Amsterdam Med Ctr, Dept Surg, Amsterdam, Netherlands. [Dong, Zhao Ming] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Nilton Felix, Valter] Univ Sao Paulo, Fac Med, Sao Paulo, Brazil. [Figueredo, Edgar; Tatum, Roger P.; Wu, Peter C.] VA Puget Sound, Dept Surg, Seattle, WA USA. [Figueredo, Edgar; Tatum, Roger P.; Wu, Peter C.] Univ Washington, Seattle, WA 98195 USA. [Gatenby, Piers A. C.; Preston, Shaun R.] Royal Surrey Cty Hosp, Guildford, Surrey, England. [Gatenby, Piers A. C.] Royal Marsden Hosp, Acad Dept Surg, London SW3 6JJ, England. [Haverkamp, Leonie; Parry, Kevin; Ruurda, Jelle P.; van der Horst, Sylvia; van der Sluis, Peter C.; van Hillegersberg, Richard] Univ Med Ctr Utrecht, Dept Surg, Utrecht, Netherlands. [Ibraev, Maksat A.; Turkin, Igor N.] RAMS, NN Blokhin Russian Canc Res Ctr, Moscow, Russia. [Krasna, Mark J.] Jersey Shore Univ, Med Ctr, Dept Oncol, Neptune, NJ USA. [Lambert, Rene] Int Agcy Res Canc, WHO, Screening Grp, F-69372 Lyon, France. [Langer, Rupert] Univ Bern, Inst Pathol, Bern, Switzerland. [Lewis, Michael P. N.; Wormald, Justin C. R.] Dept Gen Surg, Norfolk, VA USA. [Lewis, Michael P. N.; Wormald, Justin C. R.] Norwich Univ Hosp, Norwich, Norfolk, England. [Nason, Katie S.; Schaheen, Lara W.] Univ Pittsburgh, Dept Cardiothorac Surg, Pittsburgh, PA USA. RP Allum, WH (reprint author), UCL, Div Surg & Intervent Sci, London, England. EM annals@nyas.org RI Gatenby, Piers/C-1696-2008; OI Gatenby, Piers/0000-0002-1361-9940; Wormald, Justin/0000-0001-6197-4093; Bonavina, Luigi/0000-0002-4880-1670 FU NCI NIH HHS [K07 CA151613]; World Health Organization [001] NR 124 TC 6 Z9 6 U1 0 U2 3 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 1325 BP 242 EP 268 DI 10.1111/nyas.12533 PG 27 WC Oncology; Gastroenterology & Hepatology SC Oncology; Gastroenterology & Hepatology GA BB5DU UT WOS:000343712700022 PM 25266029 ER PT J AU Dolla, NK Chen, C Larkins-Ford, J Rajamuthiah, R Jagadeesan, S Conery, AL Ausubel, FM Mylonakis, E Bremner, JB Lewis, K Kelso, MJ AF Dolla, Naveen K. Chen, Chao Larkins-Ford, Jonah Rajamuthiah, Rajmohan Jagadeesan, Sakthimala Conery, Annie L. Ausubel, Frederick M. Mylonakis, Eleftherios Bremner, John B. Lewis, Kim Kelso, Michael J. TI On the Mechanism of Berberine-INF55 (5-Nitro-2-phenylindole) Hybrid Antibacterials SO AUSTRALIAN JOURNAL OF CHEMISTRY LA English DT Article ID INHIBITORS; PUMP; DERIVATIVES; INDOLES; AGENTS AB Berberine-INF55 hybrids are a promising class of antibacterials that combine berberine and the NorA multidrug resistance pump inhibitor INF55 (5-nitro-2-phenylindole) together in one molecule via a chemically stable linkage. Previous studies demonstrated the potential of these compounds for countering efflux-mediated antibacterial drug resistance but they didn't establish whether the compounds function as originally intended, i.e. with the berberine moiety providing antibacterial activity and the attached INF55 component independently blocking multidrug resistance pumps, thereby enhancing the activity of berberine by reducing its efflux. We hypothesised that if the proposed mechanism is correct, then hybrids carrying more potent INF55 pump inhibitor structures should show enhanced antibacterial effects relative to those bearing weaker inhibitors. Two INF55 analogues showing graded reductions in NorA inhibitory activity compared with INF55 were identified and their corresponding berberine-INF55 hybrids carrying equivalent INF55 inhibitor structures synthesised. Multiple assays comparing the antibacterial effects of the hybrids and their corresponding berberine-INF55 analogue combinations showed that the three hybrids all show very similar activities, leading us to conclude that the antibacterial mechanism(s) of berberine-INF55 hybrids is different from berberine-INF55 combinations. C1 [Dolla, Naveen K.; Bremner, John B.; Kelso, Michael J.] Univ Wollongong, Sch Chem, Wollongong, NSW 2522, Australia. [Chen, Chao; Lewis, Kim] Northeastern Univ, Dept Biol, Boston, MA 02115 USA. [Chen, Chao; Lewis, Kim] Northeastern Univ, Antimicrobial Discovery Ctr, Boston, MA 02115 USA. [Larkins-Ford, Jonah; Jagadeesan, Sakthimala; Conery, Annie L.; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Rajamuthiah, Rajmohan; Mylonakis, Eleftherios] Brown Univ, Rhode Isl Hosp, Dept Med, Div Infect Dis,Warren Alpert Med Sch, Providence, RI 02903 USA. [Jagadeesan, Sakthimala; Conery, Annie L.; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Kelso, MJ (reprint author), Univ Wollongong, Sch Chem, Wollongong, NSW 2522, Australia. EM mkelso@uow.edu.au RI Chen, Chao/J-7879-2015; OI Kelso, Michael/0000-0001-7809-6637 FU US National Institutes of Health [R01 AI076372, P01 AI083214] FX We gratefully acknowledge the US National Institutes of Health (grant numbers R01 AI076372 and P01 AI083214) for funding this work and we thank all of the universities involved for their support. NR 19 TC 6 Z9 6 U1 1 U2 3 PU CSIRO PUBLISHING PI COLLINGWOOD PA 150 OXFORD ST, PO BOX 1139, COLLINGWOOD, VICTORIA 3066, AUSTRALIA SN 0004-9425 EI 1445-0038 J9 AUST J CHEM JI Aust. J. Chem. PY 2014 VL 67 IS 10 BP 1471 EP 1480 DI 10.1071/CH14426 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA AR8OB UT WOS:000343833400015 ER PT S AU Dobrev, I Harrington, EJ Cheng, T Furlong, C Rosowski, JJ AF Dobrev, I. Harrington, E. J. Cheng, T. Furlong, C. Rosowski, J. J. BE Furlong, C Gorecki, C DeGroot, PJ Novak, EL TI High-speed holographic system for full-field transient vibrometry of the human tympanic membrane SO INTERFEROMETRY XVII: ADVANCED APPLICATIONS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Interferometry XVII - Advanced Applications CY AUG 18-20, 2014 CL San Diego, CA SP SPIE DE Acoustic-solid interaction; High-speed cameras; High-speed holography; Local phase correlation; Otology; Transient response; Tympanic membrane ID MIDDLE-EAR; MOTION; EMISSIONS; SURFACE AB Understanding of the human hearing process requires the quantification of the transient response of the human ear and the human tympanic membrane (TM or eardrum) in particular. Current state-of-the-art medical methods to quantify the transient acousto-mechanical response of the TM provide only averaged acoustic or local information at a few points. This may be insufficient to fully describe the complex patterns unfolding across the full surface of the TM. Existing engineering systems for full-field nanometer measurements of transient events, typically based on holographic methods, constrain the maximum sampling speed and/or require complex experimental setups. We have developed and implemented of a new high-speed (i.e., > 40 Kfps) holographic system (HHS) with a hybrid spatio-temporal local correlation phase sampling method that allows quantification of the full-field nanometer transient (i.e., > 10 kHz) displacement of the human TM. The HHS temporal accuracy and resolution is validated versus a LDV on both artificial membranes and human TMs. The high temporal (i.e., < 24 mu s) and spatial (i.e., > 100k data points) resolution of our HHS enables simultaneous measurement of the time waveform of the full surface of the TM. These capabilities allow for quantification of spatially-dependent motion parameters such as energy propagation delays surface wave speeds, which can be used to infer local material properties across the surface of the TM. The HHS could provide a new tool for the investigation of the auditory system with applications in medical research, in-vivo clinical diagnosis as well as hearing aids design. C1 [Dobrev, I.; Harrington, E. J.; Furlong, C.] Worcester Polytech Inst, Dept Mech Engn, Ctr Holog Studies & Laser MicromechaTron CHSLT, Worcester, MA 01609 USA. Massachusetts Eye & Ear Infirm, Boston, MA USA. [Rosowski, J. J.] 3 Speech & Hearing Bioscience & Technol, Cambridge, MA USA. RP Dobrev, I (reprint author), Worcester Polytech Inst, Dept Mech Engn, Ctr Holog Studies & Laser MicromechaTron CHSLT, Worcester, MA 01609 USA. FU National Institute on Deafness and Other Communication Disorders (NIDCD); National Institute of Health (NIH); Massachusetts Eye and Ear Infirmary (MEEI); Mittal Fund; Eaton-Peabody Laboratory (EPL) of the Massachusetts Eye and Ear Infirmary (MEEI); Center for Holographic Studies and Laser micro-mechaTronics (CHSLT); Worcester Polytechnic Institute FX This work has been funded by the National Institute on Deafness and Other Communication Disorders (NIDCD), the National Institute of Health (NIH), the Massachusetts Eye and Ear Infirmary (MEEI), and the Mittal Fund. The authors should like to acknowledge the help of Michael Ravicz at the Eaton-Peabody Laboratory (EPL) of the Massachusetts Eye and Ear Infirmary (MEEI), Ellery Harrington, and Morteza Khaleghi at the Center for Holographic Studies and Laser micro-mechaTronics (CHSLT) at Worcester Polytechnic Institute. NR 15 TC 0 Z9 0 U1 1 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-231-4 J9 PROC SPIE PY 2014 VL 9204 AR UNSP 920405 DI 10.1117/12.2063523 PG 6 WC Optics; Physics, Applied SC Optics; Physics GA BB5HK UT WOS:000343873800004 ER PT S AU Khaleghi, M Furlong, C Cheng, JT Rosowski, JJ AF Khaleghi, Morteza Furlong, Cosme Cheng, Jeffrey Tao Rosowski, John J. BE Furlong, C Gorecki, C DeGroot, PJ Novak, EL TI Shape and 3D acoustically-induced vibrations of the human eardrum characterized by digital holography SO INTERFEROMETRY XVII: ADVANCED APPLICATIONS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Interferometry XVII - Advanced Applications CY AUG 18-20, 2014 CL San Diego, CA SP SPIE DE 3D displacement measurements; Digital holography; Hearing research; Shape measurements; Tympanic Membrane ID TYMPANIC-MEMBRANE; MOTION AB The eardrum or Tympanic Membrane (TM) transfers acoustic energy from the ear canal (at the external ear) into mechanical motions of the ossicles (at the middle ear). The acousto-mechanical-transformer behavior of the TM is determined by its shape and mechanical properties. For a better understanding of hearing mysteries, full-field-of-view techniques are required to quantify shape, nanometer-scale sound-induced displacement, and mechanical properties of the TM in 3D. In this paper, full-field-of-view, three-dimensional shape and sound-induced displacement of the surface of the TM are obtained by the methods of multiple wavelengths and multiple sensitivity vectors with lensless digital holography. Using our developed digital holographic systems, unique 3D information such as, shape (with micrometer resolution), 3D acoustically-induced displacement (with nanometer resolution), full strain tensor (with nano-strain resolution), 3D phase of motion, and 3D directional cosines of the displacement vectors can be obtained in full-field-of-view with a spatial resolution of about 3 million points on the surface of the TM and a temporal resolution of 15 Hz. C1 [Khaleghi, Morteza; Furlong, Cosme] Worcester Polytech Inst, Dept Mech Engn, Ctr Holog Studies & Laser MicromechaTron CHSLT, Worcester, MA 01609 USA. Harvard Med Sch, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Khaleghi, M (reprint author), Worcester Polytech Inst, Dept Mech Engn, Ctr Holog Studies & Laser MicromechaTron CHSLT, Worcester, MA 01609 USA. FU National Institute on Deafness and Other Communication Disorders (NIDCD); National Institute of Health (NIH); Massachusetts Eye and Ear Infirmary (MEEI); Mittal Fund; CHSLT labs and Eaton-Peabody Labs at MEEI FX This work has been funded by the National Institute on Deafness and Other Communication Disorders (NIDCD), the National Institute of Health (NIH), and the Massachusetts Eye and Ear Infirmary (MEEI), and the Mittal Fund. The authors also gratefully acknowledge the support of all of the members of the CHSLT labs and Eaton-Peabody Labs at MEEI, in particular, Ivo Dobrev, Ellery Harrington, and Mike Ravicz. NR 12 TC 0 Z9 0 U1 0 U2 4 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-231-4 J9 PROC SPIE PY 2014 VL 9204 AR UNSP 920404 DI 10.1117/12.2063521 PG 6 WC Optics; Physics, Applied SC Optics; Physics GA BB5HK UT WOS:000343873800003 ER PT J AU Al Hazzouri, AZ Yaffe, K AF Al Hazzouri, Adina Zeki Yaffe, Kristine TI Arterial Stiffness and Cognitive Function in the Elderly SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Review DE Aging; arterial stiffness; cognitive decline; dementia; epidemiology ID PULSE-WAVE VELOCITY; HEART-RATE-VARIABILITY; ALL-CAUSE MORTALITY; BLOOD-PRESSURE; OLDER-ADULTS; ESSENTIAL-HYPERTENSION; CARDIOVASCULAR EVENTS; INDEPENDENT PREDICTOR; AORTIC STIFFNESS; CALCIUM SCORE AB Cognitive decline and dementia are a major cause of disability and mortality among older adults. Cross-sectional evidence from observational studies suggests that greater arterial stiffness is associated with worse cognitive performance. These associations have been observed on measures of global cognition and across multiple domains of cognition. Epidemiologic evidence on the association between arterial stiffness and rate of cognitive decline has been less definitive, and very few studies have investigated the risk of developing dementia. This review summarizes the current research on arterial stiffness and cognition, issues around measurement, and the effect that potential intervention might have on the course of cognitive aging. The evidence on pharmacological and non-pharmacological (exercise, nutrition, etc.) interventions in older adults with arterial stiffness is promising. Yet there are no studies or trials that directly evaluate how interventions of arterial stiffness reduce or prevent cognitive impairment and risk of developing dementia. More research is needed to elucidate the causal link between arterial stiffness and cognitive decline and dementia, and to identify whether potential interventions to prevent or reduce arterial stiffness may benefit cognitive health of the elderly. C1 [Al Hazzouri, Adina Zeki] Univ Miami, Dept Publ Hlth Sci, Div Epidemiol & Populat Hlth, Miami, FL 33136 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Al Hazzouri, AZ (reprint author), Univ Miami, Dept Publ Hlth Sci, Div Epidemiol & Populat Hlth, 1120 NW 14th St,9th Floor, Miami, FL 33136 USA. EM axz122@miami.edu FU NIH, National Institute on Aging [K01AG047273]; National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI [KL2TR000143] FX Dr. Zeki Al Hazzouri was supported by a grant from the NIH, National Institute on Aging (K01AG047273) and the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number KL2TR000143. NR 65 TC 8 Z9 8 U1 0 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2014 VL 42 SU 4 BP S503 EP S514 DI 10.3233/JAD-141563 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AR9KQ UT WOS:000343893000019 ER PT J AU Walker, MA Volpi, S Sims, KB Walter, JE Traggiai, E AF Walker, Melissa A. Volpi, Stefano Sims, Katherine B. Walter, Jolan E. Traggiai, Elisabetta TI Powering the Immune System: Mitochondria in Immune Function and Deficiency SO JOURNAL OF IMMUNOLOGY RESEARCH LA English DT Review ID T-CELL-ACTIVATION; FATTY-ACID-METABOLISM; NF-KAPPA-B; GLYCOLYTIC METABOLISM; LYMPHOCYTE ACTIVATION; ANTIVIRAL IMMUNITY; MEMORY DEVELOPMENT; ATP RELEASE; DISEASE; PROTEIN AB Mitochondria are critical subcellular organelles that are required for several metabolic processes, including oxidative phosphorylation, as well as signaling and tissue-specific processes. Current understanding of the role of mitochondria in both the innate and adaptive immune systems is expanding. Concurrently, immunodeficiencies arising from perturbation of mitochondrial elements are increasingly recognized. Recent observations of immune dysfunction and increased incidence of infection in patients with primary mitochondrial disorders further support an important role for mitochondria in the proper function of the immune system. Here we review current findings. C1 [Walker, Melissa A.; Sims, Katherine B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Volpi, Stefano] Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, I-16147 Genoa, Italy. [Walter, Jolan E.] Massachusetts Gen Hosp Children, Dept Pediat, Div Allergy & Immunol, Boston, MA 02114 USA. [Traggiai, Elisabetta] Novartis Inst Res Biomed, Basel, Switzerland. RP Walker, MA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM walker.melissa@mgh.harvard.edu; elisabetta.traggiai@novartis.com NR 76 TC 9 Z9 10 U1 1 U2 8 PU HINDAWI PUBLISHING CORP 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 164309 DI 10.1155/2014/164309 PG 8 WC Immunology SC Immunology GA AS4XQ UT WOS:000344277800001 ER PT J AU Zhu, ZH Golay, HG Barbie, DA AF Zhu, Zehua Golay, Hadrien G. Barbie, David A. TI Targeting pathways downstream of KRAS in lung adenocarcinoma SO PHARMACOGENOMICS LA English DT Review DE autophagy; AZD6244; CYT387; cytokines; KRAS; lung cancer; OSI-906; PI3K; RAF; RAL-GEF ID SYNTHETIC LETHAL INTERACTION; RAS-INDUCED TRANSFORMATION; K-RAS; MEK INHIBITION; CELLULAR-TRANSFORMATION; DISSOCIATION STIMULATOR; PANCREATIC-CANCER; SIGNALING PATHWAY; TUMOR INITIATION; PLASMA-MEMBRANE AB Oncogenic KRAS activation is responsible for the most common genetic subtype of lung cancer. Although many of the major downstream signaling pathways that KRAS engages have been defined, these discoveries have yet to translate into effective targeted therapy. Much of the current focus has been directed at inhibiting the activation of RAF/MAPK and PI3K/AKT signaling, but clinical trials combining multiple different agents that target these pathways have failed to show significant activity. In this article, we will discuss the evidence for RAF and PI3K as key downstream RAS effectors, as well as the RAL guanine exchange factor, which is equally essential for transformation. Furthermore, we will delineate alternative pathways, including cytokine activation and autophagy, which are co-opted by oncogenic RAS signaling and also represent attractive targets for therapy. Finally, we will present strategies for combining inhibitors of these downstream KRAS signaling pathways in a rational fashion, as multitargeted therapy will be required to achieve a cure. C1 [Zhu, Zehua; Golay, Hadrien G.; Barbie, David A.] Dana Farber Canc Inst, Dept Med Oncol & Canc Biol, Boston, MA 02215 USA. [Zhu, Zehua; Barbie, David A.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Golay, Hadrien G.] Ecole Polytech Fed Lausanne, Swiss Fed Inst Technol Lausanne, Sch Life Sci, CH-1015 Lausanne, Switzerland. RP Barbie, DA (reprint author), Dana Farber Canc Inst, Dept Med Oncol & Canc Biol, 450 Brookline Ave, Boston, MA 02215 USA. EM dbarbie@partners.org FU NIH [K08 CA138918-01A1] FX DA Barbie is supported by the NIH grant K08 CA138918-01A1, Uniting against Lung Cancer, and the GTM Fund for Lung Cancer Research. Z Zhu has been supported by a Uniting against Lung Cancer Award. DA Barbie is a consultant for NofOne. 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.; No writing assistance was utilized in the production of this manuscript. NR 82 TC 10 Z9 10 U1 1 U2 7 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 EI 1744-8042 J9 PHARMACOGENOMICS JI Pharmacogenomics PY 2014 VL 15 IS 11 BP 1507 EP 1518 DI 10.2217/PGS.14.108 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AR8CD UT WOS:000343802200011 PM 25303301 ER PT J AU Valenza, G Citi, L Scilingo, EP Barbieri, R AF Valenza, Gaetano Citi, Luca Scilingo, Enzo Pasquale Barbieri, Riccardo GP IEEE TI Defining an Instantaneous Complexity Measure for Heartbeat Dynamics: the Inhomogeneous Point-process Entropy SO 2014 8TH CONFERENCE OF THE EUROPEAN STUDY GROUP ON CARDIOVASCULAR OSCILLATIONS (ESGCO) LA English DT Proceedings Paper CT 8th Conference of the European-Study-Group-on-Cardiovascular-Oscillations (ESGCO) CY MAY 25-28, 2014 CL Trento, ITALY SP Univ Studi Trento, Biomed Technologies, Univ Studi Milano, Provincia Autonoma Trento & Bruno Kessler Fdn, Healthcare Res Implementat Program, European Soc Hypertens, IEEE EMBS, European Study Grp Cardiovascular Oscillat ID APPROXIMATE ENTROPY; RATE-VARIABILITY AB Complexity measures have been widely used to characterize the nonlinear nature of cardiovascular control and heartbeat dynamics. Current approaches associate these measures to finite single values within an observation window, thus not being able to characterize instantaneous system dynamics. In this study, we introduce the definition of novel measures of entropy based on the inhomogeneous point-process theory and inspired by the approximate and sample entropy algorithms. The discrete heartbeat series are modeled through probability density functions defined at each moment in time, which characterize and predict the next beat occurrence as a function of the past history through Laguerre expansions of the Wiener-Volterra terms. Experimental results, obtained from the analysis of RR interval series extracted from five ECG recordings during postural and tilt-table maneuvers, suggest that the proposed entropy indices can provide instantaneous tracking of the heartbeat complexity and allow for further definition of the "complexity variability" framework. C1 [Valenza, Gaetano; Citi, Luca; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. RP Valenza, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM g.valenza@ieee.org; lciti@neurostat.mit.edu; e.scilingo@centropiaggio.unipi.it; barbieri@neurostat.mit.edu RI Citi, Luca/G-2270-2011 OI Citi, Luca/0000-0001-8702-5654 NR 14 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-3969-5 PY 2014 BP 27 EP 28 PG 2 WC Engineering, Biomedical SC Engineering GA BB5AO UT WOS:000343599700014 ER PT J AU Valenza, G Orini, M Citi, L Minchole, A Pueyo, E Laguna, P Barbieri, R AF Valenza, Gaetano Orini, Michele Citi, Luca Minchole, Ana Pueyo, Ester Laguna, Pablo Barbieri, Riccardo GP IEEE TI Assessing Instantaneous QT Variability dynamics within a Point-Process Nonlinear Framework SO 2014 8TH CONFERENCE OF THE EUROPEAN STUDY GROUP ON CARDIOVASCULAR OSCILLATIONS (ESGCO) LA English DT Proceedings Paper CT 8th Conference of the European-Study-Group-on-Cardiovascular-Oscillations (ESGCO) CY MAY 25-28, 2014 CL Trento, ITALY SP Univ Studi Trento, Biomed Technologies, Univ Studi Milano, Provincia Autonoma Trento & Bruno Kessler Fdn, Healthcare Res Implementat Program, European Soc Hypertens, IEEE EMBS, European Study Grp Cardiovascular Oscillat ID HEART-RATE; REPOLARIZATION LABILITY; INTERVAL VARIABILITY; ECG AB The importance of cardiac repolarization dynamics in promoting arrhythmic events is widely recognized. To this extent, mathematical modeling and signal processing have played an important role in providing effective measures related to cardiac and autonomic nervous system dynamics. In this study, we introduce an instantaneous assessment of QT variability indices using a point-process nonlinear framework. The analysis includes computation of the dynamical spectrum and bispectrum, as well as time domain features, from data gathered from healthy subjects undergoing a tilt test trial. We demonstrate that an inverse-Gaussian probability function effectively predicts the current QT interval given a nonlinear combination of the past QT intervals modeled through the Laguerre expansion of the Wiener-Volterra terms. Results also show that our approach is able to provide an accurate instantaneous characterization of ventricular repolarization dynamics during changes with posture. C1 [Valenza, Gaetano; Barbieri, Riccardo] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Valenza, Gaetano] Univ Pisa, Dept Informat Engin, Res Ctr, Pisa, Italy. [Citi, Luca] UCL, Inst Cardiovascular Sci, London, England. [Citi, Luca] Univ Essex, Sch Comp Sci & Elect Engn, Colchester, Essex, England. [Minchole, Ana] Univ Oxford, Comp Sci Dptm, Oxford, England. [Pueyo, Ester; Laguna, Pablo] Univ Zaragoza, GTC, Arag Inst Engn, Zaragoza, Spain. RP Valenza, G (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM g.valenza@ieee.org RI Citi, Luca/G-2270-2011; OI Citi, Luca/0000-0001-8702-5654; Barbieri, Riccardo/0000-0001-9381-3833; orini, michele/0000-0001-5773-0344; Valenza, Gaetano/0000-0001-6574-1879; laguna, Pablo/0000-0003-3434-9254 FU Department of Anesthesia; Critical Care Pain Medicine; Massachusetts General Hospital; Harvard Medical School, Boston, MA, USA FX The research leading to these results has received partial funding from the Department of Anesthesia, Critical Care & Pain Medicine, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-3969-5 PY 2014 BP 67 EP + PG 2 WC Engineering, Biomedical SC Engineering GA BB5AO UT WOS:000343599700034 ER PT S AU Gorelick, DA Zangen, A George, MS AF Gorelick, David A. Zangen, Abraham George, Mark S. BE Uhl, GR TI Transcranial magnetic stimulation in the treatment of substance addiction SO ADDICTION REVIEWS SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE addiction; substance use disorder; TMS; transcranial magnetic stimulation; treatment ID DORSOLATERAL PREFRONTAL CORTEX; COCAINE-DEPENDENT PATIENTS; TREATMENT-RESISTANT DEPRESSION; SHAM-CONTROLLED TRIALS; HF-RTMS SESSION; BRAIN-STIMULATION; MAJOR DEPRESSION; CORTICAL EXCITABILITY; DOPAMINE RELEASE; MOTOR CORTEX AB Transcranial magnetic stimulation (TMS) is a noninvasive method of brain stimulation used to treat a variety of neuropsychiatric disorders, but is still in the early stages of study as addiction treatment. We identified 19 human studies using repetitive TMS (rTMS) to manipulate drug craving or use, which exposed a total of 316 adults to active rTMS. Nine studies involved tobacco, six alcohol, three cocaine, and one methamphetamine. The majority of studies targeted high-frequency (5-20 Hz; expected to stimulate neuronal activity) rTMS pulses to the dorsolateral prefrontal cortex. Only five studies were controlled clinical trials: two of four nicotine trials found decreased cigarette smoking; the cocaine trial found decreased cocaine use. Many aspects of optimal treatment remain unknown, including rTMS parameters, duration of treatment, relationship to cue-induced craving, and concomitant treatment. The mechanisms of rTMS potential therapeutic action in treating addictions are poorly understood, but may involve increased dopamine and glutamate function in corticomesolimbic brain circuits and modulation of neural activity in brain circuits that mediate cognitive processes relevant to addiction, such as response inhibition, selective attention, and reactivity to drug-associated cues. rTMS treatment of addiction must be considered experimental at this time, but appears to have a promising future. C1 [Gorelick, David A.] NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, Baltimore, MD USA. [Gorelick, David A.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [Zangen, Abraham] Ben Gurion Univ Negev, Dept Life Sci, IL-84105 Beer Sheva, Israel. [George, Mark S.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Gorelick, DA (reprint author), Univ Maryland, Maryland Psychiat Res Ctr, Tawes Bldg,POB 21247, Baltimore, MD 21228 USA. EM dgorelick@mprc.umaryland.edu FU Intramural NIH HHS [Z99 DA999999] NR 107 TC 26 Z9 27 U1 5 U2 16 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 1327 BP 79 EP 93 DI 10.1111/nyas.12479 D2 10.1111/nyas.12571 PG 15 WC Substance Abuse SC Substance Abuse GA BB5KA UT WOS:000343916500006 PM 25069523 ER PT J AU Jung, M Chan, CKY Viswanath, K AF Jung, Minsoo Chan, Carina Ka Yee Viswanath, Kasisomayajula TI Moderating Effects of Media Exposure on Associations between Socioeconomic Position and Cancer Worry SO ASIAN PACIFIC JOURNAL OF CANCER PREVENTION LA English DT Article DE Cancer; worry; health communication; media exposure; knowledge; communication inequalities ID PERCEIVED RISK; BREAST-CANCER; INFORMATION-SEEKING; HEALTH BEHAVIOR; UNITED-STATES; PERCEPTION; DISPARITIES; KNOWLEDGE; NEWS; METAANALYSIS AB Reducing fear of cancer is significant in developing cancer screening interventions, but the levels of fear may vary depending on the degrees of media exposure as well as individuals' socioeconomic positions (SEP). However, few studies have examined how the SEP influences the fear of cancer under the moderating process of general and specific forms of media exposure. We investigated the moderating effect of media exposure on the relationship between SEP and the level of fear of cancer by assuming that cancer knowledge is a covariate between those two. In particular, this study examined how exposure to both general and specific media changes the series of processes from SEP to fear of cancer. We conducted path analyses with three types of media - television, radio and the Internet-using data from a health communication survey of 613 adults in Massachusetts in the United States. We found that SEP influences cancer knowledge directly and fear of cancer indirectly, as moderated by the level of media exposure. Health-specific exposure, however, had a more consistent effect than general media exposure in lowering the fear of cancer by increasing knowledge about cancer. A higher level of health-specific exposure and greater amount of cancer knowledge lessened the fear of cancer. In addition, the more people were exposed to health information on television and the Internet, the lower the level of fear of cancer as a result. These findings indicate a relationship between SEP and fear of cancer, as moderated by the level and type of media exposure. Furthermore, the findings suggest that for early detection or cancer prevention strategies, health communication approaches through mass media need to be considered. C1 [Jung, Minsoo] Dongduk Womens Univ, Dept Hlth Sci, Seoul, South Korea. [Chan, Carina Ka Yee] Monash Univ, Jeffrey Cheah Sch Med & Hlth Sci, Bandar Sunway, Malaysia. [Chan, Carina Ka Yee] Australian Catholic Univ, Sydney, NSW 2059, Australia. [Viswanath, Kasisomayajula] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. RP Jung, M (reprint author), Dongduk Womens Univ, Dept Hlth Sci, Seoul, South Korea. EM mins.jung@gmail.com RI Chan, Carina/O-6258-2014 OI Chan, Carina/0000-0002-1799-7877 FU Dana-Farber Harvard Cancer Center (DFHCC-NCI) [P30CA006516]; Tobacco Research Network on Disparities (TReND); Massachusetts Department of Public Health FX This work was supported by the Dana-Farber Harvard Cancer Center (DFHCC-NCI P30CA006516), the Tobacco Research Network on Disparities (TReND), and the Massachusetts Department of Public Health for providing funding for the public opinion survey. NR 41 TC 2 Z9 2 U1 1 U2 8 PU ASIAN PACIFIC ORGANIZATION CANCER PREVENTION PI GYEONGGI-DO PA APJCP HEAD OFFICE, KOREAN NATL CANCER CENTER, 323 ILAN -RO, ILSANDONG-GU, GOYANG-SI, GYEONGGI-DO, 410-769, SOUTH KOREA SN 1513-7368 J9 ASIAN PAC J CANCER P JI Asian Pac. J. Cancer Prev. PY 2014 VL 15 IS 14 BP 5845 EP 5851 DI 10.7314/APJCP.2014.15.14.5845 PG 7 WC Oncology SC Oncology GA AR6XD UT WOS:000343723300059 PM 25081712 ER PT J AU Silverberg, ND Luoto, TM Ohman, J Iverson, GL AF Silverberg, Noah D. Luoto, Teemu M. Ohman, Juha Iverson, Grant L. TI Assessment of mild traumatic brain injury with the King-Devick Test (R) in an emergency department sample SO BRAIN INJURY LA English DT Article DE All neuropsychology/behavior; assessment of cognitive disorders/dementia; brain trauma; diagnostic test assessment; MRI ID VISUAL SCREENING TOOL; POSTTRAUMATIC AMNESIA; SPORT CONCUSSION; SYMPTOMS; TBI AB Objective: The King-Devick Test (R) (K-D) is a brief measure of cognitive processing speed and rapid gaze shifting that appears sensitive to the effects of sport-related concussion. This study evaluated its diagnostic and incremental validity in civilian patients with mild traumatic brain injury (MTBI). Methods: Participants with MTBI (n = 26) and controls with non-head injuries (n = 33) were prospectively recruited from an Emergency Department (ED). They underwent a clinical evaluation including the K-D test and the Sport Concussion Assessment Tool 2 (SCAT2). Magnetic resonance imaging (MRI) was conducted within 10 days post-injury. Results: The patients with MTBI differed from those without MTBI on components of the SCAT2, including the Symptom Scale (Cohen's d = 1.02-1.15, p<0.001) and Standardized Assessment of Concussion (d = 0.81, p = 0.004), but not the K-D test (d = 0.40, p = 0.148). In a logistic regression analysis, the K-D Test did not contribute over and above these two measures in predicting group membership (MTBI vs. control), p = 0.191. Low K-D Test scores in the MTBI group (<1 SD below controls) were not associated with poor SCAT2 performance, loss of consciousness or traumatic abnormalities on MRI, suggesting these cases may have been false positives. Conclusions: The present findings do not support the K-D Test for the assessment of civilian MTBI in an ED setting. C1 [Silverberg, Noah D.] Univ British Columbia, Dept Med, Div Phys Med & Rehabil, Vancouver, BC, Canada. [Silverberg, Noah D.] GF Strong Rehab Ctr, Vancouver, BC, Canada. [Luoto, Teemu M.; Ohman, Juha] Tampere Univ Hosp, Dept Neurosci & Rehabil, FI-33521 Tampere, Finland. [Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. RP Luoto, TM (reprint author), Tampere Univ Hosp, Dept Neurosci & Rehabil, POB 2000, FI-33521 Tampere, Finland. EM teemu.luoto@pshp.fi FU Medical Research Fund of Tampere University Hospital; Maire Taponen Foundation; Emil Aaltonen Foundation FX The authors report no conflicts of interest. This study has been supported by the Medical Research Fund of Tampere University Hospital, the Maire Taponen Foundation and the Emil Aaltonen Foundation. NR 24 TC 8 Z9 8 U1 1 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PY 2014 VL 28 IS 12 BP 1590 EP 1593 DI 10.3109/02699052.2014.943287 PG 4 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AR6UD UT WOS:000343717700010 PM 25093537 ER PT J AU Li, T Qian, Z Ter-Minassian, M Chan, JA Brais, LK Brooks, N Lin, X Christiani, DC Fuchs, CS Ogino, S Kulke, MH AF Li, T. Qian, Z. Ter-Minassian, M. Chan, J. A. Brais, L. K. Brooks, N. Lin, X. Christiani, D. C. Fuchs, C. S. Ogino, S. Kulke, M. H. TI Analysis of Somatostatin Receptors Expression in Neuroendocrine Tumors SO NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 11th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease CY MAR 05-07, 2014 CL Barcelona, SPAIN SP ENETS DE sstr2; ssa; net; os; pfs C1 [Li, T.; Qian, Z.; Ter-Minassian, M.; Chan, J. A.; Brais, L. K.; Brooks, N.; Fuchs, C. S.; Ogino, S.; Kulke, M. H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lin, X.; Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 EI 1423-0194 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2014 VL 99 IS 3-4 MA E7 BP 236 EP 236 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA AR5RB UT WOS:000343640100050 ER PT J AU Qian, Z Ter-Minassian, M Chan, JA Imamura, YU Hooshmand, SM Brais, LK Lin, X Christiani, DC Fuchs, CS Ogino, S Kulke, MH AF Qian, Z. Ter-Minassian, M. Chan, J. A. Imamura, Y. U. Hooshmand, S. M. Brais, L. K. Lin, X. Christiani, D. C. Fuchs, C. S. Ogino, S. Kulke, M. H. TI Association between Tumor Expression of VEGFA, VEGFR1 (FLT1), VEGFR2 (KDR), and Clinical Outcomes in Neuroendocrine Tumors SO NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 11th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease CY MAR 05-07, 2014 CL Barcelona, SPAIN SP ENETS DE vegf; bevacizumab; net survival C1 [Qian, Z.; Ter-Minassian, M.; Chan, J. A.; Imamura, Y. U.; Hooshmand, S. M.; Brais, L. K.; Fuchs, C. S.; Ogino, S.; Kulke, M. H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Qian, Z.; Ter-Minassian, M.; Chan, J. A.; Imamura, Y. U.; Hooshmand, S. M.; Brais, L. K.; Fuchs, C. S.; Ogino, S.; Kulke, M. H.] Harvard Univ, Sch Med, Boston, MA USA. [Lin, X.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 EI 1423-0194 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2014 VL 99 IS 3-4 MA E9 BP 237 EP 237 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA AR5RB UT WOS:000343640100052 ER PT J AU Kulke, MH O'Dorisio, T Yang, QM Jackson, J Jackson, S Boehm, KA Law, L Lapuerta, P Kostelec, J Auguste, P Sommers, R Gelhom, HL AF Kulke, M. H. O'Dorisio, T. Yang, Q. M. Jackson, J. Jackson, S. Boehm, K. A. Law, L. Lapuerta, P. Kostelec, J. Auguste, P. Sommers, R. Gelhom, H. L. TI Patient-Reported Symptom Experiences Following Participation in a Study of Telotristat Etiprate for Patients with Neuroendocrine Tumors and Diarrhea Not Adequately Controlled on Octreotide SO NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 11th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease CY MAR 05-07, 2014 CL Barcelona, SPAIN SP ENETS DE carcinoid; interview; symptom improvement C1 [Kulke, M. H.; Sommers, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [O'Dorisio, T.] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [Yang, Q. M.; Jackson, J.; Jackson, S.; Boehm, K. A.; Law, L.; Lapuerta, P.] Lexicon Pharmaceut Inc, The Woodlands, TX USA. [Kostelec, J.; Auguste, P.; Gelhom, H. L.] Evidera Bethesda Md, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 EI 1423-0194 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2014 VL 99 IS 3-4 MA M2 BP 278 EP 278 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA AR5RB UT WOS:000343640100164 ER PT J AU Wheeler, D Kulke, MH O'Dorisio, T Horsch, D Jackson, S Ye, GL Kim, HW Zambrowicz, B Sands, A Fleming, D AF Wheeler, D. Kulke, M. H. O'Dorisio, T. Hoersch, D. Jackson, S. Ye, G. L. Kim, H. W. Zambrowicz, B. Sands, A. Fleming, D. TI Telotristat Etiprate (TE) in a Cohort of Carcinoid Heart Disease Patients in Two Phase 2 Trials SO NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 11th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease CY MAR 05-07, 2014 CL Barcelona, SPAIN SP ENETS DE carcinoid; heart disease; serotonin; telotristat C1 [Wheeler, D.; Jackson, S.; Ye, G. L.; Kim, H. W.; Zambrowicz, B.; Sands, A.; Fleming, D.] Lexicon Pharmaceut Inc, The Woodlands, TX USA. [Kulke, M. H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [O'Dorisio, T.] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [Hoersch, D.] Zent Ink Bad Berke GmbH, Bad Berka, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 EI 1423-0194 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2014 VL 99 IS 3-4 MA M9 BP 281 EP 281 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA AR5RB UT WOS:000343640100171 ER PT S AU Nishida, A Lau, CW Mizoguchi, E Mizoguchi, A AF Nishida, Atsushi Lau, Cindy W. Mizoguchi, Emiko Mizoguchi, Atsushi BE Vitale, G Mion, F TI Regulatory B Cells in Mouse Models of Intestinal Inflammation SO REGULATORY B CELLS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Breg; IL-10; Inflammatory bowel disease (IBD); Gut-associated lymphoid tissues (GALT); Lamina propria lymphocyte ID GROWTH-FACTOR-BETA; ULCERATIVE-COLITIS; BOWEL-DISEASE; T-CELLS; RITUXIMAB THERAPY; MICE; RECEPTOR; ANTI-CD20; DEPLETION; SUBSET AB Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition with increasing incidence and prevalence around the world. Although B cells had generally been believed to play a pathogenic role in IBD due to the production of autoantibodies, a growing body of evidence from mouse models suggests the coexistence of pathogenic B cells and regulatory B cells, termed Breg, in this disorder. Since some unique techniques are required to closely study the Breg in gut-associated lymphoid tissues (GALT), we herein describe how to induce colitis in mice and how to analyze the phenotype and function of GALT-specific Breg. C1 [Nishida, Atsushi] Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02114 USA. [Nishida, Atsushi] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Nishida, Atsushi; Lau, Cindy W.; Mizoguchi, Atsushi] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Lau, Cindy W.; Mizoguchi, Atsushi] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Mizoguchi, Emiko] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Mizoguchi, Emiko] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Nishida, A (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI081807, R01AI081807]; NIDDK NIH HHS [R01DK091247] NR 37 TC 3 Z9 6 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1161-5; 978-1-4939-1160-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1190 BP 227 EP 241 DI 10.1007/978-1-4939-1161-5_16 D2 10.1007/978-1-4939-1161-5 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BB4SN UT WOS:000343312900017 PM 25015284 ER PT J AU Magalhaes, R Alves, J Thomas, RE Chiaravalloti, N Goncalves, OF Petrosyan, A Sampaio, A AF Magalhaes, Rosana Alves, Jorge Thomas, Roger E. Chiaravalloti, Nancy Goncalves, Oscar F. Petrosyan, Agavni Sampaio, Adriana TI Are cognitive interventions for Multiple Sclerosis effective and feasible? SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Article DE Rehabilitation; multiple sclerosis; systematic review; meta-analysis; feasibility ID RANDOMIZED CONTROLLED-TRIAL; TIMED INSTRUMENTAL ACTIVITIES; QUALITY-OF-LIFE; IMPROVES MEMORY; WORKING-MEMORY; CLINICAL-TRIAL; MS PATIENTS; NEUROPSYCHOLOGICAL REHABILITATION; OLDER ADULTS; SHORT-TERM AB Purpose: Fifty percent of patients with Multiple Sclerosis (MS) are estimated to have cognitive impairments leading to considerable decline in productivity and quality of life. Cognitive intervention has been considered to complement pharmacological treatments. However, a lack of agreement concerning the efficacy of cognitive interventions in MS still exists. A systematic review and meta-analysis was conducted to assess the effects of cognitive interventions in MS. Methods: To overcome limitations of previous meta-analyses, several databases were searched only for Randomized Clinical Trials (RCTs) with low risk of bias. Results: Five studies (total of 139 participants) met our eligibility criteria. Although good completion and adherence rates were evident, we found no evidence of intervention effects on cognition or mood in post-intervention or follow-up assessments. Conclusions: This is the first meta-analysis assessing the effects of cognitive intervention in MS including only RCTs with comparable conditions. Research regarding efficacy, cost-effectiveness and feasibility is still in its infancy. Caution is advised when interpreting these results due to the small number of RCTs meeting the inclusion criteria. Considering the costs of disease, good completion and adherence rates of this approach, further research is warranted. Recommendations concerning improved research practices in the field are presented as well. C1 [Magalhaes, Rosana; Alves, Jorge; Goncalves, Oscar F.; Petrosyan, Agavni; Sampaio, Adriana] Univ Minho, Sch Psychol, CIPsi, Neuropsychophysiol Lab, Braga, Portugal. [Thomas, Roger E.] Univ Calgary, Hlth Sci Ctr, Dept Family Med, Calgary, AB, Canada. [Chiaravalloti, Nancy] Kessler Fdn, NNL, W Orange, NJ USA. [Chiaravalloti, Nancy] Rutgers State Univ, Dept Phys Med & Rehabil, Piscataway, NJ 08855 USA. [Goncalves, Oscar F.] Northeastern Univ, Bouve Coll Hlth Sci, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. [Goncalves, Oscar F.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil,Spaulding Ctr Neuromodula, Boston, MA USA. [Goncalves, Oscar F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Petrosyan, Agavni] Univ Calif Irvine, Dept Cognit Sci, Irvine, CA 92717 USA. RP Magalhaes, R (reprint author), Univ Minho, Escola Psicol, Lab Neuropsicofisiol, Campus Gualtar, P-4710057 Braga, Portugal. EM rosana.magalhaes@psi.uminho.pt RI Magalhaes, Rosana/D-2178-2015; Goncalves, Oscar/G-5278-2010; Sampaio, Adriana/C-8361-2011 OI Magalhaes, Rosana/0000-0002-6298-5840; Goncalves, Oscar/0000-0003-2735-9155; Sampaio, Adriana/0000-0001-7347-1282 FU Fundacao para a Ciencia e Tecnologia (FCT) [SFRH/BD/65213/2009, SFRH/BD/64457/2009]; FSE/POPH; FEDER (POFC-COMPETE) [PIC/IC/83290/2007] FX R.M. and J.A. are supported by doctoral Grants from Fundacao para a Ciencia e Tecnologia (FCT) (SFRH/BD/65213/2009, SFRH/BD/64457/2009 and co-funded by FSE/POPH). A.S. is funded for the project PIC/IC/83290/2007, supported by FEDER (POFC-COMPETE) and FCT to develop and assess the effectiveness of a cognitive stimulation tool for Portuguese clinicians. NR 68 TC 2 Z9 2 U1 3 U2 16 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0922-6028 EI 1878-3627 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PY 2014 VL 32 IS 5 BP 623 EP 638 DI 10.3233/RNN-140388 PG 16 WC Neurosciences SC Neurosciences & Neurology GA AR2NP UT WOS:000343424900005 PM 25096974 ER PT J AU Goldstein, LE McKee, AC Stanton, PK AF Goldstein, Lee E. McKee, Ann C. Stanton, Patric K. TI Considerations for animal models of blast-related traumatic brain injury and chronic traumatic encephalopathy SO ALZHEIMERS RESEARCH & THERAPY LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; POSTTRAUMATIC-STRESS-DISORDER; EXPLOSIVE BLAST; INDUCED NEUROTRAUMA; APOLIPOPROTEIN-E; GENETIC-FACTORS; WAR VETERAN; BIOMARKERS; EXPOSURE; IRAQ AB The association of military blast exposure and brain injury was first appreciated in World War I as commotio cerebri, and later as shell shock. Similar injuries sustained in modern military conflicts are now classified as mild traumatic brain injury (TBI). Recent research has yielded new insights into the mechanisms by which blast exposure leads to acute brain injury and chronic sequelae, including postconcussive syndrome, post-traumatic stress disorder, post-traumatic headache, and chronic traumatic encephalopathy, a tau protein neurodegenerative disease. Impediments to delivery of effective medical care for individuals affected by blast-related TBI include: poor insight into the heterogeneity of neurological insults induced by blast exposure; limited understanding of the mechanisms by which blast exposure injures the brain and triggers sequelae; failure to appreciate interactive injuries that affect frontal lobe function, pituitary regulation, and neurovegetative homeostasis; unknown influence of genetic risk factors, prior trauma, and comorbidities; absence of validated diagnostic criteria and clinical nosology that differentiate clinical endophenotypes; and lack of empirical evidence to guide medical management and therapeutic intervention. While clinicopathological analysis can provide evidence of correlative association, experimental use of animal models remains the primary tool for establishing causal mechanisms of disease. However, the TBI field is confronted by a welter of animal models with varying clinical relevance, thereby impeding scientific coherence and hindering translational progress. Animal models of blast TBI will be far more translationally useful if experimental emphasis focuses on accurate reproduction of clinically relevant endpoints (output) rather than scaled replication of idealized blast shockwaves (input). The utility of an animal model is dependent on the degree to which the model recapitulates pathophysiological mechanisms, neuropathological features, and neurological sequelae observed in the corresponding human disorder. Understanding the purpose of an animal model and the criteria by which experimental results derived from the model are validated are critical components for useful animal modeling. Animal models that reliably demonstrate clinically relevant endpoints will expedite development of new treatments, diagnostics, preventive measures, and rehabilitative strategies for individuals affected by blast TBI and its aftermath. C1 [Goldstein, Lee E.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Goldstein, Lee E.; McKee, Ann C.] Coll Engn, Boston, MA 02118 USA. [Goldstein, Lee E.; McKee, Ann C.] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA. [McKee, Ann C.] VA Boston Healthcare Syst, US Dept Vet Affairs, Boston, MA 02130 USA. [Stanton, Patric K.] New York Med Coll, Dept Neurol, Valhalla, NY 10595 USA. [Stanton, Patric K.] New York Med Coll, Dept Cell Biol, Valhalla, NY 10595 USA. [Stanton, Patric K.] New York Med Coll, Dept Anat, Valhalla, NY 10595 USA. RP Goldstein, LE (reprint author), Boston Univ, Sch Med, 670 Albany St,4th Floor, Boston, MA 02118 USA. EM lgold@bu.edu FU NIA NIH HHS [P30 AG013846] NR 91 TC 11 Z9 11 U1 2 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-9193 J9 ALZHEIMERS RES THER JI Alzheimers Res. Ther. PY 2014 VL 6 IS 5 AR 64 DI 10.1186/s13195-014-0064-3 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AQ9TW UT WOS:000343200300010 PM 25478023 ER PT J AU Marquie, M Locascio, JJ Rentz, DM Becker, JA Hedden, T Johnson, KA Growdon, JH Gomperts, SN AF Marquie, Marta Locascio, Joseph J. Rentz, Dorene M. Becker, J. Alex Hedden, Trey Johnson, Keith A. Growdon, John H. Gomperts, Stephen N. TI Striatal and extrastriatal dopamine transporter levels relate to cognition in Lewy body diseases: an C-11 altropane positron emission tomography study SO ALZHEIMERS RESEARCH & THERAPY LA English DT Article ID PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; PREFRONTAL CORTEX; I-123-FP-CIT SPECT; CORTICAL SURFACE; CEREBRAL-CORTEX; DEMENTIA; BODIES; SYSTEM; PET AB Introduction: The biological basis of cognitive impairment in parkinsonian diseases is believed to be multifactorial. We investigated the contribution of dopamine deficiency to cognition in Parkinson disease (PD) and dementia with Lewy bodies (DLB) with dopamine transporter (DAT) imaging. Methods: We acquired C-11 altropane PET, magnetic resonance imaging and cognitive testing in 19 nondemented subjects with PD, 10 DLB and 17 healthy control subjects (HCS). We analyzed DAT concentration in putamen, caudate, anterior cingulate (AC), orbitofrontal and prefrontal regions, using the Standardized Uptake Volume Ratio with partial volume correction, and we related DAT concentration and global cortical thickness to neuropsychological performance. Results: DAT concentration in putamen and in caudate were similar in PD and DLB groups and significantly lower than in HCS. Reduced caudate DAT concentration was associated with worse Clinical Dementia Rating Scale-sum of boxes (CDR-SB) scores and visuospatial skills in DLB but not in PD or HCS groups. Adjusting for putamen DAT concentration, as a measure of severity of motor disease, caudate DAT concentration was lower in DLB than in PD. Higher AC DAT concentration was associated with lower putamen DAT concentration in DLB and with higher putamen DAT concentration in PD. Higher AC DAT concentration in DLB correlated with greater impairment in semantic memory and language. Conclusions: Caudate and AC dopamine dysfunction contribute in opposing directions to cognitive impairment in DLB. C1 [Marquie, Marta; Locascio, Joseph J.; Rentz, Dorene M.; Johnson, Keith A.; Growdon, John H.; Gomperts, Stephen N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Marquie, Marta; Gomperts, Stephen N.] MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Marquie, Marta] Autonomous Univ Barcelona, Doctoral Sch, Bellaterra 08193, Cerdanyola Del, Spain. [Rentz, Dorene M.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Becker, J. Alex; Hedden, Trey; Johnson, Keith A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hedden, Trey] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Gomperts, SN (reprint author), Massachusetts Gen Hosp, Dept Neurol, 15 Parkman St, Boston, MA 02114 USA. EM gomperts.stephen@mgh.harvard.edu OI Marquie, Marta/0000-0002-0660-0950 FU Caja Madrid Foundation scholarship for postgraduate studies (Madrid, Spain); Alzheimer Association [IIRG-08-90934]; Michael J. Fox Foundation; National Institute of Health; National Institute of Aging (K01) [AG040197]; National Institute of Health (National Institute of Aging, National Institute of Neurological Disorders and Stroke); Alzheimer Association; American Health Assistance Foundation; National Institute on Aging; National Institute of Health grants from National Institute of Mental Health [1K08MH81207]; National Institute of Aging (National Alzheimer's Coordinating Center, expired); National Institute of Neurological Disorders and Stroke [R21 NS060310]; National Alzheimer's Coordinating Center Collaborative Project [5 U01 AG016976-11]; National Institute of Neurological Disorders and Stroke; Alzheimer's Disease Association; Caja Madrid Foundation Scholarship for Postgraduate Studies; Harvard Center for Neurodegeneration and Repair Pilot grant FX The authors thank Dr Randy L Buckner, PhD, from the Cognitive Neuroscience Laboratory and Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, who provided research funding for the HCS group.; MM received research support from the Caja Madrid Foundation scholarship for postgraduate studies 2011-2013 (Madrid, Spain). JJL is a consultant for the Harvard Catalyst Bio-Statistical Consulting Group and serves on the Statistical Advisory Board of PLoS-One Journal. DMR received research support from the Alzheimer Association IIRG-08-90934 and the Michael J. Fox Foundation. JAB received research support from the National Institute of Health. TH received research support from the National Institute of Aging (K01 grant AG040197). KAJ receives research support from the Michael J. Fox Foundation, the National Institute of Health (National Institute of Aging, National Institute of Neurological Disorders and Stroke), the Alzheimer Association, and the American Health Assistance Foundation. JHG received research support from the National Institute on Aging and from the Michael J. Fox Foundation, and he served on the editorial board of JAMA Neurology, and on the Scientific Advisory Board of Neurimmune Therapeutics. SNG is funded by National Institute of Health grants from National Institute of Mental Health (1K08MH81207), the National Institute of Aging (National Alzheimer's Coordinating Center, expired), and National Institute of Neurological Disorders and Stroke (R21 NS060310, expired), and receives research support from the Michael J. Fox Foundation.; This work was supported by the Michael J. Fox Foundation (to SNG and JHG), National Alzheimer's Coordinating Center Collaborative Project 5 U01 AG016976-11 (to SNG, KAJ, and JHG), the National Institute of Neurological Disorders and Stroke (to KAJ), the National Institute on Aging (to KAJ and TH), the Alzheimer's Disease Association (to KAJ), the Caja Madrid Foundation Scholarship for Postgraduate Studies 2011-2013 (to MM), and the Harvard Center for Neurodegeneration and Repair Pilot grant (to SNG). Funding for the HCS group was supported by the National Institute of Health to Dr Randy L Buckner, who serves as a contributor to this study. This study is not industry-sponsored. NR 63 TC 5 Z9 5 U1 2 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-9193 J9 ALZHEIMERS RES THER JI Alzheimers Res. Ther. PY 2014 VL 6 IS 5 AR 52 DI 10.1186/s13195-014-0052-7 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AQ9TW UT WOS:000343200300001 PM 25429309 ER PT J AU Martinez-Ramirez, S Greenberg, SM Viswanathan, A AF Martinez-Ramirez, Sergi Greenberg, Steven M. Viswanathan, Anand TI Cerebral microbleeds: overview and implications in cognitive impairment SO ALZHEIMERS RESEARCH & THERAPY LA English DT Review ID RECURRENT INTRACEREBRAL HEMORRHAGE; T2-ASTERISK-WEIGHTED MR-IMAGES; MEMORY CLINIC POPULATION; EARLY ALZHEIMERS-DISEASE; AMYLOID ANGIOPATHY; CEREBROVASCULAR-DISEASE; ROTTERDAM-SCAN; LOBAR HEMORRHAGE; ECHO MRI; DEMENTIA AB Cerebral microbleeds (MBs) are small chronic brain hemorrhages which are likely caused by structural abnormalities of the small vessels of the brain. Owing to the paramagnetic properties of blood degradation products, MBs can be detected in vivo by using specific magnetic resonance imaging (MRI) sequences. Over the last decades, the implementation of these MRI sequences in both epidemiological and clinical studies has revealed MBs as a common finding in many different populations, including healthy individuals. Also, the topographic distribution of these MBs has been shown to be potentially associated with specific underlying vasculopathies. However, the clinical and prognostic significance of these small hemorrhages is still a matter of debate as well as a focus of extensive research. In this article, we aim to review the current knowledge on the pathophysiology and clinical implications of MBs, with special emphasis on the links between lobar MBs, cerebral amyloid angiopathy, and Alzheimer's disease. C1 [Martinez-Ramirez, Sergi; Greenberg, Steven M.; Viswanathan, Anand] Massachusetts Gen Hosp, Philip J Kistler Stroke Res Ctr, Boston, MA 02114 USA. RP Martinez-Ramirez, S (reprint author), Massachusetts Gen Hosp, Philip J Kistler Stroke Res Ctr, 175 Cambridge St Suite 300, Boston, MA 02114 USA. EM srmartinez@partners.org FU National Institutes of Health-National Institute on Aging (NIH-NIA) [5R01AG026484]; NIH-NINDS [5R01NS070834]; NIH-NIA [5P50AG005134, 5K23AG028726] FX SMG is the principal investigator in the following grants related to CAA: title: Amyloid Angiopathy, sponsor: National Institutes of Health-National Institute on Aging (NIH-NIA), sponsor number: 5R01AG026484; title: Early Detection of CAA, sponsor: NIH-NINDS, sponsor number: 5R01NS070834. AV is the principal investigator in the following grants related to CAA: title: Project II, sponsor: NIH-NIA, sponsor number: 5P50AG005134; title: Effect of WMD on Gait and Balance in CAA, sponsor: NIH-NIA, sponsor number: 5K23AG028726. SM-R declares that he has no competing interests. NR 63 TC 25 Z9 27 U1 0 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-9193 J9 ALZHEIMERS RES THER JI Alzheimers Res. Ther. PY 2014 VL 6 IS 3 AR 33 DI 10.1186/alzrt263 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AQ9TU UT WOS:000343200100010 PM 24987468 ER PT J AU Montenigro, PH Baugh, CM Daneshvar, DH Mez, J Budson, AE Au, R Katz, DI Cantu, RC Stern, RA AF Montenigro, Philip H. Baugh, Christine M. Daneshvar, Daniel H. Mez, Jesse Budson, Andrew E. Au, Rhoda Katz, Douglas I. Cantu, Robert C. Stern, Robert A. TI Clinical subtypes of chronic traumatic encephalopathy: literature review and proposed research diagnostic criteria for traumatic encephalopathy syndrome SO ALZHEIMERS RESEARCH & THERAPY LA English DT Review ID FOOTBALL-LEAGUE PLAYER; BRAIN-INJURY; ALZHEIMERS-DISEASE; PUNCH DRUNK; HEAD-INJURY; IMPACT; CONCUSSION; SPECTRUM; SPORTS AB The long-term consequences of repetitive head impacts have been described since the early 20th century. Terms such as punch drunk and dementia pugilistica were first used to describe the clinical syndromes experienced by boxers. A more generic designation, chronic traumatic encephalopathy (CTE), has been employed since the mid-1900s and has been used in recent years to describe a neurodegenerative disease found not just in boxers but in American football players, other contact sport athletes, military veterans, and others with histories of repetitive brain trauma, including concussions and subconcussive trauma. This article reviews the literature of the clinical manifestations of CTE from 202 published cases. The clinical features include impairments in mood (for example, depression and hopelessness), behavior (for example, explosivity and violence), cognition (for example, impaired memory, executive functioning, attention, and dementia), and, less commonly, motor functioning (for example, parkinsonism, ataxia, and dysarthria). We present proposed research criteria for traumatic encephalopathy syndrome (TES) which consist of four variants or subtypes (TES behavioral/mood variant, TES cognitive variant, TES mixed variant, and TES dementia) as well as classifications of 'probable CTE' and 'possible CTE'. These proposed criteria are expected to be modified and updated as new research findings become available. They are not meant to be used for a clinical diagnosis. Rather, they should be viewed as research criteria that can be employed in studies of the underlying causes, risk factors, differential diagnosis, prevention, and treatment of CTE and related disorders. C1 [Montenigro, Philip H.; Stern, Robert A.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Baugh, Christine M.; Au, Rhoda; Katz, Douglas I.; Stern, Robert A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Daneshvar, Daniel H.] Boston Univ, Sch Med, Behav Neurosci Program, Boston, MA 02118 USA. [Mez, Jesse; Budson, Andrew E.; Stern, Robert A.] Boston Univ, Sch Med, BU Alzheimers Dis Ctr, Boston, MA 02118 USA. [Budson, Andrew E.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Au, Rhoda] NHLBI, Framingham Heart Study, Boston, MA 02118 USA. [Katz, Douglas I.] Braintree Rehabil Hosp, Braintree, MA 02184 USA. [Cantu, Robert C.; Stern, Robert A.] Boston Univ, Sch Med, Dept Neurosurg, Boston, MA 02118 USA. [Cantu, Robert C.] Emerson Hosp, Dept Neurosurg, Concord, MA 01742 USA. RP Stern, RA (reprint author), Boston Univ, Sch Med, Dept Anat & Neurobiol, 72 East Concord St, Boston, MA 02118 USA. EM bobstern@bu.edu OI Daneshvar, Daniel/0000-0003-3691-9513; Stern, Robert/0000-0002-5008-077X; Montenigro, Philip/0000-0003-4442-9207 FU National Institutes of Health (NIH) [R01 NS078337, P30 AG13846, U01NS086659, AG016495-11, NS17950, AG08122, AG029451, AG033040, AG033193, HL096917/, DARPA-BAA-11-65, R01 MH080295, R01 CA129769, U01 NS086659]; US Department of Defense [W81XWH-13-2-0064]; US Department of Veterans Affairs FX The authors wish to thank the following individuals for their contributions to this article: Nathan Fritts, Michael McClean, David Riley, Clifford Robbins, Daniel Seichepine, Julie Stamm, Yorghos Tripodis, and Florina Tynyanova. The preparation and writing of this article were supported, in part, through the following: National Institutes of Health (NIH) grants R01 NS078337 and P30 AG13846 and US Department of Defense grant W81XWH-13-2-0064. These funding agencies played no role in the writing of the manuscript or the decision to submit it. DHD and JM receive funding through NIH grant U01NS086659. AEB receives funding through NIH grant P30 AG13846 and the US Department of Veterans Affairs. RA receives funding through NIH grants AG016495-11, NS17950, AG08122, AG029451, AG033040, AG033193, HL096917/, and DARPA-BAA-11-65. RAS receives funding through NIH grants R01 NS078337, R01 MH080295, R01 CA129769, U01 NS086659, and P30 AG13846 and US Department of Defense grant W81XWH-13-2-0064. PHM, CMB, DIK, and RCC receive no external funding. NR 60 TC 28 Z9 28 U1 5 U2 21 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-9193 J9 ALZHEIMERS RES THER JI Alzheimers Res. Ther. PY 2014 VL 6 IS 5 AR 68 DI 10.1186/s13195-014-0068-z PG 17 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AQ9TW UT WOS:000343200300013 PM 25580160 ER PT S AU Lau, AM Tseng, YH Schulz, TJ AF Lau, Anne-Marie Tseng, Yu-Hua Schulz, Tim J. BE Christ, B Oerlecke, J Stock, P TI Adipogenic Fate Commitment of Muscle-Derived Progenitor Cells: Isolation, Culture, and Differentiation SO ANIMAL MODELS FOR STEM CELL THERAPY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Skeletal muscle; Adipogenic progenitors; Fluorescence-activated cell sorting; Cell surface marker antibodies; Brown adipogenesis; Bone morphogenetic protein 7 ID SKELETAL-MUSCLE; STEM-CELLS; SATELLITE CELLS; FIBRO/ADIPOGENIC PROGENITORS; DYSTROPHIC MUSCLES; PREPLATE TECHNIQUE; WHITE FAT; EXPRESSION; IDENTIFICATION; REGENERATION AB Skeletal muscle harbors several types of cells, among which a population of progenitors committed to the adipogenic lineage has only recently been identified. Potential sources of white and brown adipocytes, the latter representing a potential target to treat obesity, are of considerable interest to the field. Fluorescence-activated cell sorting (FACS) provides an elegant strategy for prospective isolation of closely defined cell populations. Here we describe a flow cytometric method to isolate muscle-resident adipogenic progenitor cells with a default potential to undergo white adipogenesis. We further describe an approach to induce commitment to a lineage of brown-like adipocytes upon exposure to bone morphogenetic protein 7 (BMP7). C1 [Lau, Anne-Marie; Schulz, Tim J.] German Inst Human Nutr, Res Grp Adipocyte Dev, Nuthetal, Germany. [Tseng, Yu-Hua] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Lau, AM (reprint author), German Inst Human Nutr, Res Grp Adipocyte Dev, Nuthetal, Germany. OI Schulz, Tim/0000-0002-8413-3972 FU NIDDK NIH HHS [R01 DK077097] NR 31 TC 1 Z9 1 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 978-1-4939-1453-1; 978-1-4939-1452-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1213 BP 229 EP 243 DI 10.1007/978-1-4939-1453-1_19 D2 10.1007/978-1-4939-1453-1 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell & Tissue Engineering; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA BB3MZ UT WOS:000342900700020 PM 25173387 ER PT J AU Stewart, MH AF Stewart, Morag. H. TI Pluripotency and Targeted Reprogramming: Strategies, Disease Modeling and Drug Screening SO CURRENT DRUG DELIVERY LA English DT Article DE Directed differentiation; disease modeling; drug screening; embryonic stem cells; induced pluripotent cells; induced somatic cells; patient specific; reprogramming ID EMBRYONIC STEM-CELLS; PRIMORDIAL GERM-CELLS; HUMAN SOMATIC-CELLS; DEFINED FACTORS; MOUSE EMBRYOS; IN-VITRO; SELF-RENEWAL; HEMATOPOIETIC DIFFERENTIATION; TERATOCARCINOMA CELLS; MONOCLONAL-ANTIBODY AB Pluripotent stem cell research has developed over the last fifty years from the study of embryonic development to a multifaceted discipline that encompasses development, epigenetics, reprogramming, cell therapy, disease modeling and chemical and drug screening. The idea of patient-specific therapies and disease modeling using human pluripotent stem cells has been the theoretical golden-egg of the field since the generation of human embryonic stem cells. With the advent of induced pluripotent stem cells (PSCs), the ability to generate patient-specific cells for therapeutic use, to model disease progression and to test drugs on disease relevant cells moved a large step closer to reality. While there still is a long way to go before the results of PSC research is found in the clinic or in the pharmacy, recent developments have demonstrated that it is possible to generate patient-specific pluripotent cells which can differentiate into disease relevant cell types, are amenable to gene correction, can phenocopy molecular and functional disease characteristics, at least in vitro, and can be used to validate the efficacy of therapeutic compounds. This review will cover recent developments in the generation and manipulation of pluripotent stem cells with a focus on the use of pluripotent stem cells for disease modeling and therapeutic drug screening. In addition, the latest developments in somatic cell reprogramming will also be discussed. C1 [Stewart, Morag. H.] Boston Childrens Hosp Mol, Program Cellular & Mol Med, Boston, MA 02115 USA. [Stewart, Morag. H.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Stewart, MH (reprint author), Boston Childrens Hosp Mol, Program Cellular & Mol Med, Boston, MA 02115 USA. EM morag.stewart@childrens.harvard.edu FU Kay Kendall Leukemia Fund; Junior Research Fellowship; Merton College, University of Oxford FX M.H.S is supported through a research fellowship from the Kay Kendall Leukemia Fund and a Junior Research Fellowship with Merton College, University of Oxford. M.H.S is grateful for helpful discussions and comments from Tariq Ever and Kevin Eggan. NR 142 TC 1 Z9 1 U1 1 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2018 EI 1875-5704 J9 CURR DRUG DELIV JI Curr. Drug Deliv. PY 2014 VL 11 IS 5 BP 592 EP 604 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AQ9HD UT WOS:000343159400006 PM 23517625 ER PT J AU Shoni, M Lui, KO Vavvas, DG Muto, MG Berkowitz, RS Vlahos, N Ng, SW AF Shoni, Melina Lui, Kathy O. Vavvas, Demetrios G. Muto, Michael G. Berkowitz, Ross S. Vlahos, Nikolaos Ng, Shu-Wing TI Protein Kinases and Associated Pathways in Pluripotent State and Lineage Differentiation SO CURRENT STEM CELL RESEARCH & THERAPY LA English DT Article DE Endothelial cells; phosphorylation; pluripotency; protein kinases; signaling pathways; stem cell ID EMBRYONIC STEM-CELLS; FIBROBLAST-GROWTH-FACTOR; ENDOTHELIAL PROGENITOR CELLS; RECEPTOR TYROSINE KINASE; LEUKEMIA INHIBITORY FACTOR; HUMAN SOMATIC-CELLS; SELF-RENEWAL; BETA-CATENIN; IN-VITRO; SIGNAL-TRANSDUCTION AB Protein kinases (PKs) mediate the reversible conversion of substrate proteins to phosphorylated forms, a key process in controlling intracellular signaling transduction cascades. Pluripotency is, among others, characterized by specifically expressed PKs forming a highly interconnected regulatory network that culminates in a finely-balanced molecular switch. Current high-throughput phosphoproteomic approaches have shed light on the specific regulatory PKs and their function in controlling pluripotent states. Pluripotent cell-derived endothelial and hematopoietic developments represent an example of the importance of pluripotency in cancer therapeutics and organ regeneration. This review attempts to provide the hitherto known kinome profile and the individual characterization of PK-related pathways that regulate pluripotency. Elucidating the underlying intrinsic and extrinsic signals may improve our understanding of the different pluripotent states, the maintenance or induction of pluripotency, and the ability to tailor lineage differentiation, with a particular focus on endothelial cell differentiation for anti-cancer treatment, cell-based tissue engineering, and regenerative medicine strategies. C1 [Shoni, Melina; Muto, Michael G.; Berkowitz, Ross S.; Ng, Shu-Wing] Harvard Univ, Sch Med, Dana Farber Canc Inst,Div Gynecol Oncol, Brigham & Womens Hosp,Dept Obstet & Gynecol, Boston, MA 02115 USA. [Lui, Kathy O.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Vavvas, Demetrios G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis Lab, Boston, MA USA. [Vlahos, Nikolaos] Univ Athens, Sch Med, Aretaie Gen Hosp, Dept Obstet & Gynecol, GR-11527 Athens, Greece. RP Ng, SW (reprint author), 221 Longwood Ave,BLI-449A, Boston, MA 02115 USA. EM sng@partners.org RI Lui, Kathy O./E-4883-2015; OI Lui, Kathy O./0000-0002-1616-3643; Vavvas, Demetrios/0000-0002-8622-6478 FU Ruth N. White Gynecologic Oncology Research Fund; Robert and Deborah First Fund; Sperling Family Fund Foundation; Ovarian Cancer Research Foundation; Adler Foundation, Inc.; Friends of Dana-Farber Cancer Institute; Women's Cancer Program and Gillette Center for Women's Cancer from Dana-Farber Cancer Institute FX The Gynecologic Oncology Laboratory at Brigham and Women's Hospital is supported by Ruth N. White Gynecologic Oncology Research Fund, Robert and Deborah First Fund, the Sperling Family Fund Foundation, Women's Cancer Program and Gillette Center for Women's Cancer from Dana-Farber Cancer Institute, Ovarian Cancer Research Foundation, Adler Foundation, Inc., and the Friends of Dana-Farber Cancer Institute. NR 375 TC 0 Z9 0 U1 2 U2 11 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1574-888X EI 2212-3946 J9 CURR STEM CELL RES T JI Curr. Stem Cell Res. Ther. PY 2014 VL 9 IS 5 BP 366 EP 387 PG 22 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA AQ9WT UT WOS:000343209400002 PM 24998240 ER PT J AU Wei, FL Wang, CL Wang, ZX Kong, YW Shi, Y Shi, JQ Qi, DL Qi, HF Liang, J Zhang, RQ Li, CZ AF Wei, Fulei Wang, Chenlong Wang, Zhaoxi Kong, Yawei Shi, Yuan Shi, Jianquan Qi, Delin Qi, Hongfang Liang, Jian Zhang, Rongqing Li, Changzhong TI Cloning and characterization of two subunits of calcineurin cDNA in naked carp (Gymnocypris przewalskii) from Lake Qinghai, China SO FOLIA HISTOCHEMICA ET CYTOBIOLOGICA LA English DT Article DE Gymnocypris przewalskii; calcineurin; embryogenesis; calcineurin subunits; cloning; cDNA; IHC; Qinghai Lake ID DEPENDENT PROTEIN PHOSPHATASE; OYSTER-PINCTADA-FUCATA; RAT-BRAIN; A-ALPHA; EMBRYONIC-DEVELOPMENT; CARDIAC-HYPERTROPHY; REGULATORY SUBUNIT; MOLECULAR-CLONING; CALCIUM-CHANNEL; CALMODULIN AB The naked carp (Gymnocypris przewalskii), a native teleost, plays an important role in maintenance of the ecological balance in the system of Lake Qinghai (altitude, 3.2 km) on the Qinghai-Tibet Plateau in China. Calcineurin (CN) is the only member of the serine/threonine phosphatase family that can be activated by both Ca2+ and calmodulin (CaM) and involved in many important physiological processes such as salt tolerance//adaption. In this report, cDNAs of CN catalytic subunit paralogue isoforms: GpCA alpha (GenBank accession no. JQ407043), GpCA gamma (GenBank accession no. JQ407043), and CN regulatory subunit (GpCB) (GenBank accession no. JQ410473), were isolated from Gymnocypris przewalskii and their expression patterns in embryos development were characterized. Gene expression profile demonstrated that GpCA and GpCB mRNA was distributed ubiquitously in all embryonic stages and showed decline until final stage of development. Immunohistological analysis revealed CN localization in different tissues including kidney, heart, brain, spermary, and gill. Collectively, these results provide molecular basis and clues to further understand the role of CN during embryos development and its function in tissues for the adaptation mechanism of naked carp. C1 [Wei, Fulei; Wang, Chenlong; Wang, Zhaoxi; Shi, Yuan; Liang, Jian; Zhang, Rongqing; Li, Changzhong] Qinghai Univ, Coll Ecoenvironm Engn, Xining 810016, Peoples R China. [Kong, Yawei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA USA. [Shi, Jianquan; Qi, Hongfang] Emergency Ctr Gymnocypris Przewalskii, Xining, Peoples R China. [Qi, Delin] Qinghai Univ, Coll Agr & Anim Husb, Xining 810016, Peoples R China. RP Li, CZ (reprint author), Qinghai Univ, Coll Ecoenvironm Engn, Xining 810016, Peoples R China. EM lichangzhong@qhu.edu.cn FU Program of National Fisheries Resources Platform of China; Qinghai Science and Technology Department, Qinghai province, China [2013-Z-715]; Qinghai University [2011-QNZ-1] FX This work was financially supported by the Program of National Fisheries Resources Platform of China, the applied background research project from Qinghai Science and Technology Department, Qinghai province, China (2013-Z-715), and the research project at Qinghai University (2011-QNZ-1). NR 53 TC 1 Z9 1 U1 0 U2 4 PU VIA MEDICA PI GDANSK PA UL SWIETOKRZYSKA 73, 80-180 GDANSK, POLAND SN 0239-8508 EI 1897-5631 J9 FOLIA HISTOCHEM CYTO JI Folia Histochem. Cytobiol. PY 2014 VL 52 IS 3 BP 232 EP 243 DI 10.5603/FHC.2014.0027 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AQ8EC UT WOS:000343055500009 PM 25308739 ER PT S AU Chen, DZ Craft, D Yang, L AF Chen, Danny Z. Craft, David Yang, Lin BE Chen, J Hopcroft, JE Wang, J TI A Circular Matrix-Merging Algorithm with Application in VMAT Radiation Therapy SO FRONTIERS IN ALGORITHMICS, FAW 2014 SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 8th International Frontiers of Algorithmics Workshop (FAW) CY JUN 28-30, 2014 CL Zhangjiajie, PEOPLES R CHINA SP Cent S Univ, Natl Natl Sci Fdn China ID MODULATED ARC THERAPY; MULTILEAF COLLIMATORS; DELIVERY EFFICIENCY; HELICAL TOMOTHERAPY; OPTIMIZATION; IMRT; QUALITY AB In this paper, we study an optimization problem, called the circular matrix-merging (CMM) problem: Given a cyclic sequence of n non-negative matrices that are associated with some locations on a circle and an operation that merges two consecutive matrices into one matrix at the expense of some merging error, merge the n matrices into the minimum number of matrices under the constraint of a threshold of the total merging error. This problem arises in Volumetric Intensity-Modulated Arc Therapy (VMAT) for radiation cancer treatment, where the circular structure represents a delivery arc path of 360 degrees around the patient and the matrices represent the radiation fluence maps at selected delivery angles on that path. By computing the minimum k matrices, the CMM algorithm produces a most efficient delivery plan that meets clinical requirements. Based on dynamic programming and computing a set of k-link shortest paths, we present a polynomial time algorithm for the CMM problem, improving the quality and efficiency of VMAT delivery. C1 [Chen, Danny Z.; Yang, Lin] Univ Notre Dame, Dept Comp Sci & Engn, Notre Dame, IN 46556 USA. [Craft, David] Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiat Oncol, Boston, MA 02114 USA. RP Yang, L (reprint author), Univ Notre Dame, Dept Comp Sci & Engn, Notre Dame, IN 46556 USA. EM dchen@nd.edu; dcraft@partners.org; lyang5@nd.edu FU NSF [CCF-1217906] FX This research was supported in part by NSF under Grant CCF-1217906. NR 13 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 978-3-319-08016-1; 978-3-319-08015-4 J9 LECT NOTES COMPUT SC PY 2014 VL 8497 BP 36 EP 47 PG 12 WC Computer Science, Theory & Methods SC Computer Science GA BB3TW UT WOS:000343048600004 ER PT S AU Kashiwagi, M Kitabata, H Akasaka, T Tearney, GJ AF Kashiwagi, Manabu Kitabata, Hironori Akasaka, Takashi Tearney, Guillermo J. BE Nicholls, SJ Crowe, T TI Optical Coherence Tomography of Coronary Atherosclerosis SO IMAGING CORONARY ATHEROSCLEROSIS SE Contemporary Cardiology LA English DT Article; Book Chapter ID DRUG-ELUTING STENTS; INTRAVASCULAR ULTRASOUND GUIDANCE; ELEVATION MYOCARDIAL-INFARCTION; THIN-CAP FIBROATHEROMA; GUIDE DECISION-MAKING; IN-VIVO; PLAQUE CHARACTERISTICS; BARE-METAL; ANGINA-PECTORIS; ARTERY-DISEASE C1 [Kashiwagi, Manabu] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Kitabata, Hironori; Akasaka, Takashi] Med Univ, Dept Cardiovasc Med, Wakayama 6418509, Japan. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Tearney, GJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, 40 Parkman St,RSL 160, Boston, MA 02114 USA. EM mkashiwagi2@partners.org; miu1205@hotmail.co.jp; akasat@wakayama-med.ac.jp; gtearney@partners.org NR 52 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 SN 1191-7601 BN 978-1-4939-0572-0; 978-1-4939-0571-3 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2014 BP 105 EP 118 DI 10.1007/978-1-4939-0572-0_8 D2 10.1007/978-1-4939-0572-0 PG 14 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA BB3MV UT WOS:000342899500009 ER PT S AU Jaffer, FA Libby, P AF Jaffer, Farouc A. Libby, Peter BE Nicholls, SJ Crowe, T TI Molecular Imaging of Coronary Atherosclerosis SO IMAGING CORONARY ATHEROSCLEROSIS SE Contemporary Cardiology LA English DT Article; Book Chapter ID POSITRON-EMISSION-TOMOGRAPHY; OXIDATION-SPECIFIC EPITOPES; EARLY-STAGE ATHEROSCLEROSIS; CELL-ADHESION MOLECULE-1; IN-VIVO; IRON-OXIDE; VASCULAR INFLAMMATION; PLAQUE; MACROPHAGES; ANTIBODIES C1 [Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA 02115 USA. [Libby, Peter] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA. RP Libby, P (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, 77 Ave Louis Pasteur,NRB-741, Boston, MA 02115 USA. EM plibby@partners.org NR 45 TC 0 Z9 0 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1191-7601 BN 978-1-4939-0572-0; 978-1-4939-0571-3 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2014 BP 187 EP 202 DI 10.1007/978-1-4939-0572-0_14 D2 10.1007/978-1-4939-0572-0 PG 16 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA BB3MV UT WOS:000342899500015 ER PT J AU Mckee, KE Hackney, ME AF McKee, Kathleen E. Hackney, Madeleine E. TI The Four Square Step Test in individuals with Parkinson's disease: Association with executive function and comparison with older adults SO NEUROREHABILITATION LA English DT Article DE Parkinson's disease; mobility limitation; cognition; accidental falls ID MILD COGNITIVE IMPAIRMENT; CLINICAL-TEST; BALANCE; PEOPLE; MOTOR; RELIABILITY; SCALE; VALIDITY; QUESTIONNAIRE; DEMENTIA AB BACKGROUND: In Parkinson's disease (PD), motor and cognitive impairments interact to affect functional performance adversely. A valid mobility test, the Four Square Step Test (FSST) involves multidirectional stepping over obstacles. FSST performance may also be associated with cognitive performance. OBJECTIVES: This study determined the feasibility and reliability of an obstacle-based FSST in older individuals with versus without PD, and evaluated the association of PD performance of FSST with tests of cognition. METHODS: Thirty-one individuals with mild-moderate PD, evaluated while ON medications, completed the obstacle-based FSST, other mobility and cognitive measures. FSST performance was compared between a PD participant sub-set (n = 24) and 24 age-matched older adults. Data were analyzed with independent t-tests, correlations, and linear regression. RESULTS: Obstacle-based FSST was feasible and reliable within sessions in those with PD. Median best FSST time among individuals with PD was 11.72 s (9.99, 13.98) and FSST had concurrent validity with tests of mobility, and cognitive dual-tasking. Among cognitive tests, Trails Making Test B, which evaluates executive function, emerged as a sole contributor (49%) of variance. FSST performance did not differ between those with PD and older adults. CONCLUSION: The obstacle-based FSST is feasible and reliable in those with PD. The relationship between cognitive status and performance on the FSST did not appear to be strongly disease-stage dependent. Using FSST in the clinic may help assess the health status of a motor-cognitive interaction in individuals with PD. C1 [McKee, Kathleen E.] Emory Univ, Sch Med, Atlanta, GA USA. [McKee, Kathleen E.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hackney, Madeleine E.] Atlanta Vet Affairs Rehabil R&D Ctr Excellence Vi, Atlanta, GA USA. [Hackney, Madeleine E.] Emory Univ, Sch Med, Dept Med, Div Gen Med & Geriatr, Atlanta, GA USA. RP Hackney, ME (reprint author), Atlanta VA Med Ctr, Rehab R&D Ctr 151R, Div Gen Med & Geriatr Res Hlth Sci, 1670 Clairmont Rd 12C145, Decatur, GA 30033 USA. EM mehackn@emory.edu RI Nathalie, Zimmermann/M-2179-2014 FU Dan and Merrie Boone Foundation; Emory Center for Injury Control; Emory Center for Health in Aging; National Center for Advancing Translational Sciences of the National Institutes of Health [UL1TR000454]; Emory School of Medicine Discovery Program; Department of VA R&D Service Career Development Awards [E7108M, N0870 W] FX There are no conflicts of interest. The study sponsors played no role in the study design, collection, analysis and interpretation of data, the writing of the manuscript, the final conclusions drawn, or in the decision to submit the manuscript for publication. The Dan and Merrie Boone Foundation, the Emory Center for Injury Control, and the Emory Center for Health in Aging supported the study. This study was also supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000454. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The Emory School of Medicine Discovery Program supported KE McKee, and Department of VA R&D Service Career Development Awards (E7108M and N0870 W) supported ME Hackney. NR 39 TC 6 Z9 6 U1 1 U2 11 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1053-8135 EI 1878-6448 J9 NEUROREHABILITATION JI Neurorehabilitation PY 2014 VL 35 IS 2 BP 279 EP 289 DI 10.3233/NRE-141122 PG 11 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AQ7OE UT WOS:000343007000013 PM 24990034 ER PT J AU Korenjak, M Kwon, E Morris, RT Anderssen, E Amzallag, A Ramaswamy, S Dyson, NJ AF Korenjak, Michael Kwon, Eunjeong Morris, Robert T. Anderssen, Endre Amzallag, Arnaud Ramaswamy, Sridhar Dyson, Nicholas J. TI dREAM co-operates with insulator-binding proteins and regulates expression at divergently paired genes SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MYB-MUVB/DREAM COMPLEX; DROSOPHILA-BITHORAX COMPLEX; CHROMATIN INSULATOR; NUCLEAR-ORGANIZATION; EPIGENETIC REGULATION; TUMOR-SUPPRESSOR; ACTIVE PROMOTERS; FACTOR BEAF; GENOME; TRANSCRIPTION AB dREAM complexes represent the predominant form of E2F/RBF repressor complexes in Drosophila. dREAM associates with thousands of sites in the fly genome but its mechanism of action is unknown. To understand the genomic context in which dREAM acts we examined the distribution and localization of Drosophila E2F and dREAM proteins. Here we report a striking and unexpected overlap between dE2F2/dREAM sites and binding sites for the insulator-binding proteins CP190 and Beaf-32. Genetic assays show that these components functionally co-operate and chromatin immunoprecipitation experiments on mutant animals demonstrate that dE2F2 is important for association of CP190 with chromatin. dE2F2/dREAM binding sites are enriched at divergently transcribed genes, and the majority of genes upregulated by dE2F2 depletion represent the repressed half of a differentially expressed, divergently transcribed pair of genes. Analysis of mutant animals confirms that dREAM and CP190 are similarly required for transcriptional integrity at these gene pairs and suggest that dREAM functions in concert with CP190 to establish boundaries between repressed/activated genes. Consistent with the idea that dREAM co-operates with insulator-binding proteins, genomic regions bound by dREAM possess enhancer-blocking activity that depends on multiple dREAM components. These findings suggest that dREAM functions in the organization of transcriptional domains. C1 [Korenjak, Michael; Morris, Robert T.; Anderssen, Endre; Amzallag, Arnaud; Ramaswamy, Sridhar; Dyson, Nicholas J.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Korenjak, Michael; Morris, Robert T.; Anderssen, Endre; Amzallag, Arnaud; Ramaswamy, Sridhar; Dyson, Nicholas J.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Kwon, Eunjeong] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Dyson, NJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM Dyson@helix.mgh.harvard.edu FU National Institutes of Health [R01CA64402, GM053203] FX National Institutes of Health [R01CA64402 and GM053203 to N.J.D.]. NR 85 TC 6 Z9 6 U1 1 U2 6 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 14 BP 8939 EP 8953 DI 10.1093/nar/gku609 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AQ9ZH UT WOS:000343219200017 PM 25053843 ER PT J AU Raghavan, S Vassy, JL AF Raghavan, Sridharan Vassy, Jason L. TI Do physicians think genomic medicine will be useful for patient care? SO PERSONALIZED MEDICINE LA English DT Review DE clinical utility; genomic medicine; genomic testing; pharmacogenomics; physician perspectives ID RANDOMIZED-TRIAL; CLINICAL-PRACTICE; RISK-FACTORS; INTEGRATION; WARFARIN; EXPERIENCE; DIAGNOSIS; KNOWLEDGE; DELIVERY; PROJECT AB Significant technological improvements over the last decade have led to a vast expansion in the understanding of the genomic architecture of human disease. However, the use of genomic information, so-called genomic medicine, in routine clinical care, has been slow in comparison to the growth in genomic discovery. The uptake of genomic technology into clinical practice will depend on physicians' perspectives of its utility in patient care. We review recent literature addressing physician attitudes regarding the usefulness and limitations of genomic testing. We conclude by proposing research areas to better understand the role physicians will play in the uptake of genomic information into clinical medicine. C1 [Raghavan, Sridharan] Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. [Raghavan, Sridharan] Harvard Univ, Sch Med, Boston, MA USA. [Vassy, Jason L.] VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA 02130 USA. [Vassy, Jason L.] Brigham & Womens Hosp, Dept Med, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Vassy, Jason L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Raghavan, S (reprint author), Massachusetts Gen Hosp, Div Gen Med, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM sraghavan2@partners.org FU United States National Institutes of Health (NIH) [U01 HG006500]; NIH [L30 DK089597]; NIH National Research Service Award [T32HP10251]; Ryoichi Sasakawa Fellowship Fund FX This work was supported by United States National Institutes of Health (NIH) grant U01 HG006500 (JL Vassy), NIH grant L30 DK089597 (JL Vassy), NIH National Research Service Award T32HP10251 (S Raghavan) and the Ryoichi Sasakawa Fellowship Fund (S Raghavan). 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 42 TC 3 Z9 3 U1 0 U2 6 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 EI 1744-828X J9 PERS MED JI Pers. Med. PY 2014 VL 11 IS 4 BP 425 EP 433 DI 10.2217/PME.14.25 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AQ9NX UT WOS:000343183600013 PM 26161114 ER PT J AU Lin, YS Boninger, M Worobey, L Farrokhi, S Koontz, A AF Lin, Yen-Sheng Boninger, Michael Worobey, Lynn Farrokhi, Shawn Koontz, Alicia TI Effects of Repetitive Shoulder Activity on the Subacromial Space in Manual Wheelchair Users SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID SPINAL-CORD-INJURY; PAIN INDEX WUSPI; ADULT OMNI SCALE; IMPINGEMENT SYNDROME; ROTATOR CUFF; GLENOHUMERAL KINEMATICS; PERCEIVED EXERTION; EXTERNAL ROTATION; ELECTROMYOGRAPHIC ANALYSIS; SCAPULAR KINEMATICS AB This study investigated (1) the effect of repetitive weight-relief raises (WR) and shoulder external rotation (ER) on the acromiohumeral distance (AHD) among manual wheelchair users (MWUs) and (2) the relationship between shoulder pain, subject characteristics, and AHD changes. Twenty-three MWUs underwent ultrasound imaging of the nondominant shoulder in an unloaded baseline position and while holding a WR position before and after the WR/ER tasks. Paired t-tests and Spearman correlational analysis were used to assess differences in the AHD before and after each task and the relationships between pain, subject characteristics, and the AHD measures. A significant reduction in the subacromial space (P < 0.01) occurred when subjects performed a WR position compared to baseline. Individuals with increased years of disability had greater AHD percentage narrowing after WR (P = 0.008). Increased shoulder pain was associated with AHD percentage narrowing after ER (P <= 0.007). The results support clinical practice guidelines that recommend MWUs limit WR to preserve shoulder function. The isolated repetitive shoulder activity did not contribute to the changes of subacromial space in MWUs. The ultrasonographic measurement of the AHD may be a target for identifying future interventions that prevent pain. C1 [Lin, Yen-Sheng; Boninger, Michael; Worobey, Lynn; Farrokhi, Shawn; Koontz, Alicia] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. [Lin, Yen-Sheng; Boninger, Michael; Koontz, Alicia] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. [Boninger, Michael; Farrokhi, Shawn; Koontz, Alicia] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15261 USA. [Boninger, Michael; Worobey, Lynn] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA. [Farrokhi, Shawn] Univ Pittsburgh, Dept Phys Therapy, Pittsburgh, PA 15260 USA. RP Koontz, A (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. EM akoontz@pitt.edu OI Worobey, Lynn/0000-0001-8795-6061; Boninger, Michael/0000-0001-6966-919X FU Department of Veterans Affairs Rehabilitation Research and Development Service [B6789C]; Paralyzed Veterans of America; US Department of Education [H133N110011] FX This material is based upon work supported by the Department of Veterans Affairs Rehabilitation Research and Development Service (Grant no. B6789C), the Paralyzed Veterans of America, and US Department of Education (Grant no. H133N110011). This material is the result of work supported with resources and the use of facilities at the Human Engineering Research Laboratories, VA Pittsburgh Healthcare System. The contents of this paper do not represent the views of the Department of Veterans Affairs or the United States Government. An extended abstract was presented in student scientific paper winner session of 2012 Rehabilitation Engineering and Assistive Technology Society in North America annual conference. NR 50 TC 0 Z9 0 U1 0 U2 5 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 583951 DI 10.1155/2014/583951 PG 9 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AQ6RI UT WOS:000342941100001 ER PT S AU Cavelti-Weder, C Li, WD Weir, GC Zhou, Q AF Cavelti-Weder, Claudia Li, Weida Weir, Gordon C. Zhou, Qiao BE Kidder, BL TI Direct Lineage Conversion of Pancreatic Exocrine to Endocrine Beta Cells In Vivo with Defined Factors SO STEM CELL TRANSCRIPTIONAL NETWORKS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Pancreatic exocrine to beta-cell reprogramming; Transcription factors; Polycistronic gene expression; Adenovirus production and injection; Diabetes induction in mice; Blood glucose and insulin monitoring ID PROGENITOR CELLS; MOUSE PANCREAS; ALPHA-CELLS; REGENERATION; EXPRESSION; NEOGENESIS; MICE AB Pancreatic exocrine cells can be directly converted to insulin(+) beta cells by adenoviral-mediated expression of three transcription factors Pdx1, Mafa, and Ngn3 in the adult mouse pancreas (Zhou et al., Nature 455(7213):627-632, 2008). This direct reprogramming approach offers a strategy to replenish beta-cell mass and may be further developed as a potential future treatment for diabetes. Here, we provide a detailed protocol for inducing exocrine to beta-cell reprogramming in mice. We also describe key analyses we routinely use to assess the phenotype and function of reprogrammed cells. C1 [Cavelti-Weder, Claudia; Weir, Gordon C.] Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. [Li, Weida; Zhou, Qiao] Harvard Univ, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Cavelti-Weder, C (reprint author), Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. NR 20 TC 7 Z9 7 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 978-1-4939-0512-6; 978-1-4939-0511-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1150 BP 247 EP 262 DI 10.1007/978-1-4939-0512-6_17 D2 10.1007/978-1-4939-0512-6 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BB3MP UT WOS:000342896100018 PM 24744004 ER PT S AU Ouyang, JS Petibon, Y Huang, C Reese, TG Kolnick, AL El Fakhri, G AF Ouyang, Jinsong Petibon, Yoann Huang, Chuan Reese, Timothy G. Kolnick, Aleksandra L. El Fakhri, Georges BE George, T Islam, MS Dutta, AK TI Quantitative Simultaneous PET-MR Imaging SO MICRO- AND NANOTECHNOLOGY SENSORS, SYSTEMS, AND APPLICATIONS VI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Micro- and Nanotechnology Sensors, Systems, and Applications VI CY MAY 05-09, 2014 CL Baltimore, MD SP SPIE DE PET-MR; motion correction; attenuation correction; point spread function modeling ID WHOLE-BODY PET/MRI; RESPIRATORY MOTION CORRECTION; ATTENUATION CORRECTION; EMISSION-TOMOGRAPHY; RECONSTRUCTION; LIVER; MODEL; TRANSFORMATION; COMPENSATION; FEASIBILITY AB Whole-body PET is currently limited by the degradation due to patient motion. Respiratory motion degrades imaging studies of the abdomen. Similarly, both respiratory and cardiac motions significantly hamper the assessment of myocardial ischemia and/or metabolism in perfusion and viability cardiac PET studies. Based on simultaneous PET-MR, we have developed robust and accurate MRI methods allowing the tracking and measurement of both respiratory and cardiac motions during abdominal or cardiac studies. Our list-mode iterative PET reconstruction framework incorporates the measured motion fields into PET emission system matrix as well as the time-dependent PET attenuation map and the position dependent point spread function. Our method significantly enhances the PET image quality as compared to conventional methods. C1 [Ouyang, Jinsong; Petibon, Yoann; Huang, Chuan; Kolnick, Aleksandra L.; El Fakhri, Georges] Massachusetts Gen Hosp, Dept Imaging, Div Nucl Med & Mol Imaging, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. RP Ouyang, JS (reprint author), Massachusetts Gen Hosp, Dept Imaging, Div Nucl Med & Mol Imaging, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. OI Huang, Chuan/0000-0001-6052-0663 NR 38 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-020-4 J9 PROC SPIE PY 2014 VL 9083 AR 908325 DI 10.1117/12.2051578 PG 9 WC Nanoscience & Nanotechnology; Optics; Physics, Applied SC Science & Technology - Other Topics; Optics; Physics GA BB2VW UT WOS:000342426300051 ER PT J AU Leutwyler, H Hubbard, E Jeste, D Miller, B Vinogradov, S AF Leutwyler, H. Hubbard, E. Jeste, D. Miller, B. Vinogradov, S. TI Association between schizophrenia symptoms and neurocognition on mobility in older adults with schizophrenia SO AGING & MENTAL HEALTH LA English DT Article DE schizophrenia and paranoid disorders; functional status; cognitive functioning ID CONSENSUS COGNITIVE BATTERY; MEDICAL COMORBIDITY; PHYSICAL-ACTIVITY; MENTAL-ILLNESS; CARDIOVASCULAR RISK; PROCESSING SPEED; EXCESS MORTALITY; HEALTH; GAIT; CARE AB Objectives: Older persons with schizophrenia develop problems associated with aging, such as poor mobility, at more rapid rates than people without serious mental illness. Decrements in mobility contribute to poor health outcomes. Impaired neurocognitive function and psychiatric symptoms are central aspects of schizophrenia. The purpose of this study was to determine the association between neurocognitive impairment and schizophrenia symptoms to mobility in older adults with schizophrenia. Methods: A cross-sectional study with 46 older adults with schizophrenia. Participants were assessed on neurocognitive function (MATRICS Consensus Cognitive Battery), psychiatric symptoms (Positive and Negative Syndrome Scale or PANSS), and mobility (Timed Get Up and Go or TGUG test). Pearson's bivariate correlations (two-tailed) and a simultaneous regression model were used. Results: Lower severity of negative symptoms and faster speed of processing tests were associated with faster TGUG time in bivariate correlations and multivariate regression analyses (p<.05). Conclusion: Our data suggest that lower negative symptoms and faster speed of processing positively impact mobility in older patients with schizophrenia. Mobility interventions for this population need to target neurocognitive impairment and schizophrenia symptoms for optimal results. C1 [Leutwyler, H.; Hubbard, E.] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94107 USA. [Jeste, D.] Univ Calif San Diego, Sam & Rose Stein Inst Res Aging, San Diego, CA 92103 USA. [Miller, B.] Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA USA. [Vinogradov, S.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Vinogradov, S.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Leutwyler, H (reprint author), Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94107 USA. EM heather.leutwyler@nursing.ucsf.edu FU UCSF Academic Senate; National Center for Advancing Translational Sciences, National Institutes of Health through UCSF-CTSI [KL2TR000143]; National Institute of Nursing Research [P30-NR011934-0] FX This work was supported by the UCSF Academic Senate [Individual Investigator Grant]; National Center for Advancing Translational Sciences, National Institutes of Health through UCSF-CTSI [grant number KL2TR000143]; and the National Institute of Nursing Research [grant number P30-NR011934-0] to H. Leutwyler. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 51 TC 0 Z9 0 U1 4 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1360-7863 EI 1364-6915 J9 AGING MENT HEALTH JI Aging Ment. Health PY 2014 VL 18 IS 8 BP 1006 EP 1012 DI 10.1080/13607863.2014.903467 PG 7 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AP7XP UT WOS:000342291900008 PM 24697281 ER PT J AU Capron, AM Danovitch, GM Delmonico, FL AF Capron, Alexander M. Danovitch, Gabriel M. Delmonico, Francis L. TI Organ Markets: Problems Beyond Harms to Vendors SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID DONATION; TRANSPLANTATION; TRAFFICKING C1 [Capron, Alexander M.] Univ So Calif, Los Angeles, CA 90089 USA. [Danovitch, Gabriel M.] Univ Calif Los Angeles, Los Angeles, CA USA. [Delmonico, Francis L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Capron, AM (reprint author), Univ So Calif, USC Gould Sch Law, Los Angeles, CA 90089 USA. EM acapron@law.usc.edu NR 9 TC 3 Z9 3 U1 0 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2014 VL 14 IS 10 BP 23 EP 25 DI 10.1080/15265161.2014.947048 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA AP7YX UT WOS:000342295800009 PM 25229575 ER PT J AU Belstrom, D Fiehn, NE Nielsen, CH Holmstrup, P Kirkby, N Klepac-Ceraj, V Paster, BJ Twetman, S AF Belstrom, D. Fiehn, N. -E. Nielsen, C. H. Holmstrup, P. Kirkby, N. Klepac-Ceraj, V. Paster, B. J. Twetman, S. TI Altered Bacterial Profiles in Saliva from Adults with Caries Lesions: A Case-Cohort Study SO CARIES RESEARCH LA English DT Article DE 16S rRNA; Bacteria; Biomarker; Caries; Human Oral Microbe Identification Microarray; Saliva ID EARLY-CHILDHOOD CARIES; DENTAL-CARIES; MICROBIAL PROFILES; ORAL MICROBIOTA; HEALTH; MICROARRAY; CHILDREN; DIVERSITY; DENTITION AB The aim of this study was to learn whether presence of caries in an adult population was associated with a salivary bacterial profile different from that of individuals without untreated caries. Stimulated saliva samples from 621 participants of the Danish Health Examination Survey were analyzed using the Human Oral Microbe Identification Microarray technology. Samples from 174 individuals with dental caries and 447 from a control cohort were compared using frequency and levels of identified bacterial taxa/clusters as endpoints. Differences at taxon/cluster level were analyzed using Mann-Whitney's test with Benjamini-Hochberg correction for multiple comparisons. Principal component analysis was used to visualize bacterial community profiles. A reduced bacterial diversity was observed in samples from subjects with dental caries. Five bacterial taxa (Veillonella parvula, Veillonella atypica, Megasphaera micronuciformis, Fusobacterium periodontium and Achromobacter xylosoxidans) and one bacterial cluster (Leptotrichia sp. clones C3MKM102 and GT018_ot417/462) were less frequently found in the caries group (adjusted p value <0.01) while two bacterial taxa (Solobacterium moorei and Streptococcus salivarius) and three bacterial clusters (Streptococcus parasanguinis I and II and sp. clone BE024_ot057/411/721, Streptococcus parasanguinis I and II and sinensis_ot411/721/767, Streptococcus salivarius and sp. clone FO042_ot067/755) were present at significantly higher levels (adjusted p value <0.01). The principal component analysis displayed a marked difference in the bacterial community profiles between groups. Presence of manifest caries was associated with a reduced diversity and an altered salivary bacterial community profile. Our data support recent theories that ecological stress-induced changes of commensal microbial communities are involved in the shift from oral health to tooth decay. (C) 2014 S. Karger AG, Basel C1 [Belstrom, D.; Holmstrup, P.] Univ Copenhagen, Fac Hlth & Med Sci, Sect Periodontol, Dept Odontol, DK-2200 Copenhagen N, Denmark. [Fiehn, N. -E.] Univ Copenhagen, Fac Hlth & Med Sci, Dept Int Hlth Immunol & Microbiol, DK-2200 Copenhagen N, Denmark. [Twetman, S.] Univ Copenhagen, Fac Hlth & Med Sci, Dept Odontol, Sect Cariol & Endodont, DK-2200 Copenhagen N, Denmark. [Nielsen, C. H.] Copenhagen Univ Hosp, Rigshosp, Inst Inflammat Res, Dept Infect Dis & Rheumatol, Copenhagen, Denmark. [Kirkby, N.] Copenhagen Univ Hosp, Rigshosp, Dept Clin Microbiol, Copenhagen, Denmark. [Klepac-Ceraj, V.] Wellesley Coll, Dept Biol Sci, Wellesley, MA 02181 USA. [Paster, B. J.] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. [Paster, B. J.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Belstrom, D (reprint author), Univ Copenhagen, Fac Hlth & Med Sci, Sect Periodontol, Dept Odontol, Norre Alle 20, DK-2200 Copenhagen N, Denmark. EM dbel@sund.ku.dk OI Klepac-Ceraj, Vanja/0000-0001-5387-5706 FU Danish Dental Association; Danish Foundation for Mutual Efforts in Dental Care; TrygFonden; Health Insurance Foundation; Simon Spies Foundation FX This study was supported by external financial support by: the Danish Dental Association, the Danish Foundation for Mutual Efforts in Dental Care, TrygFonden, the Health Insurance Foundation and the Simon Spies Foundation. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 30 TC 15 Z9 16 U1 0 U2 15 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6568 EI 1421-976X J9 CARIES RES JI Caries Res. PY 2014 VL 48 IS 5 BP 368 EP 375 DI 10.1159/000357502 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AP9HC UT WOS:000342388600003 PM 24643218 ER PT J AU Waring, JD Seiger, AN Solomon, PR Budson, AE Kensinger, EA AF Waring, Jill D. Seiger, Ashley N. Solomon, Paul R. Budson, Andrew E. Kensinger, Elizabeth A. TI Memory for the 2008 presidential election in healthy ageing and mild cognitive impairment SO COGNITION & EMOTION LA English DT Article DE Event memory; Flashbulb memory; MCI; Ageing; Emotional memory ID ALZHEIMERS ASSOCIATION WORKGROUPS; FLASHBULB MEMORIES; OLDER-ADULTS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; RECOGNITION MEMORY; TERRORIST ATTACKS; SEPTEMBER 11; DISEASE; AGE AB The present study examined memory accuracy and confidence for personal and public event details of the 2008 presidential election in healthy older adults and those with mild cognitive impairment (MCI). Participants completed phone interviews within a week after the election and after a 10-month delay. MCI patients and healthy older adults had comparable emotional reactions to learning the outcome of the election, with most people finding it to be a positive experience. After the delay period, details about the election were better remembered by all participants than a less emotionally arousing comparison event. However, MCI patients had more difficulty than healthy older adults correctly recalling details of public information about the election, although often the MCI patients could recognise the correct details. This is the first study to show that MCI patients' memory can benefit from emotionally arousing positive events, complementing the literature demonstrating similar effects for negative events. C1 [Waring, Jill D.] VA Palo Alto Healthcare Syst, Sierra Pacific Mental Illness Res Educ & Clin Ctr, Palo Alto, CA 94304 USA. [Waring, Jill D.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Waring, Jill D.; Kensinger, Elizabeth A.] Boston Coll, Dept Psychol, Chestnut Hill, MA 02167 USA. [Seiger, Ashley N.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Solomon, Paul R.] Williams Coll, Dept Psychol, Williamstown, MA 01267 USA. [Solomon, Paul R.] Memory Clin, Bennington, VT USA. [Budson, Andrew E.] VA Boston Healthcare Syst, Ctr Translat Cognit Neurosci, Boston, MA USA. [Budson, Andrew E.] Boston Univ, Sch Med, Boston Univ Alzheimers Dis Ctr, Dept Neurol, Boston, MA 02118 USA. RP Waring, JD (reprint author), VA Palo Alto Healthcare Syst, 3801 Miranda Ave MIRECC MC 151Y, Palo Alto, CA 94304 USA. EM waringj@stanford.edu FU CSRD VA [I01 CX000736]; NIA NIH HHS [P30 AG013846, P30 AG13846] NR 47 TC 1 Z9 1 U1 0 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0269-9931 EI 1464-0600 J9 COGNITION EMOTION JI Cogn. Emot. PY 2014 VL 28 IS 8 BP 1407 EP 1421 DI 10.1080/02699931.2014.886558 PG 15 WC Psychology, Experimental SC Psychology GA AP7XA UT WOS:000342290300006 PM 24533684 ER PT J AU Kalapatapu, RK Neylan, TC Regan, MC Cohen, BE AF Kalapatapu, Raj K. Neylan, Thomas C. Regan, Mathilda C. Cohen, Beth E. TI ASSOCIATION OF ALCOHOL USE BIOMARKERS AND COGNITIVE PERFORMANCE IN VETERANS WITH PROBLEMATIC ALCOHOL USE AND POSTTRAUMATIC STRESS DISORDER: DATA FROM THE MIND YOUR HEART STUDY SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article DE Alcohol use biomarkers; cognitive performance; problematic alcohol use; posttraumatic stress disorder ID SUBSTANCE-ABUSE TREATMENT; PSYCHOMETRIC PROPERTIES; TREATMENT ENTRY; PTSD CHECKLIST; NORMATIVE DATA; IMPAIRMENT; DEPRESSION; DRINKING; MEMORY; RELIABILITY AB The authors conducted a study of alcohol use biomarkers and cognitive performance among 85 veterans with problematic alcohol use and posttraumatic stress disorder (PTSD). All analyses were adjusted for demographics, depression, anxiety, and PTSD symptoms. Elevated levels of aspartate aminotransferase were associated with worse performance on the Trail Making Test Part A and Hopkins Verbal Learning Test. Two other biomarkers were not associated with any neurocognitive measures. Indirect alcohol use biomarkers (e.g., aspartate aminotransferase) may have a specific role in identifying veterans with problematic alcohol use and PTSD who show a change in psychomotor speed and immediate verbal memory performance. C1 [Kalapatapu, Raj K.; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Kalapatapu, Raj K.; Neylan, Thomas C.; Regan, Mathilda C.; Cohen, Beth E.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Neylan, Thomas C.; Cohen, Beth E.] Northern Calif Inst Res & Educ, San Francisco, CA USA. [Cohen, Beth E.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Kalapatapu, RK (reprint author), San Francisco VA Med Ctr, Dept Psychiat, Opioid Replacement Treatment Clin, 4150 Clement St,Mailstop 116F,Bldg 1, San Francisco, CA 94121 USA. EM kalapatapu.raj.k@gmail.com FU NHLBI NIH HHS [K23HL094765, K23 HL094765]; NIDA NIH HHS [K23DA034883, K23 DA034883]; NIMH NIH HHS [5R01MH073978-04, R34 MH077667, R01 MH073978] NR 53 TC 1 Z9 1 U1 4 U2 14 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0887 EI 1545-0848 J9 J ADDICT DIS JI J. Addict. Dis. PY 2014 VL 33 IS 2 BP 67 EP 76 DI 10.1080/10550887.2014.909701 PG 10 WC Substance Abuse SC Substance Abuse GA AP7XU UT WOS:000342292500001 PM 24717141 ER PT J AU Zhang, QX Wang, CN Zhao, WJ AF Zhang, Quanxuan Wang, Changning Zhao, Wenjun TI Recent Development in Asymmetric Synthesis of Homo-allylic Amines Catalyzed by Small Organic Molecules SO MINI-REVIEWS IN ORGANIC CHEMISTRY LA English DT Article DE Allylation of imines; aminoallylation of aldehydes; Bronsted acid catalysis; Homo-allylic amines; organoboronate reagents ID NEUTRAL-COORDINATE-ORGANOCATALYSTS; ENANTIOSELECTIVE ENE REACTIONS; PI-ALLYLPALLADIUM COMPLEX; AZA-COPE REARRANGEMENT; ALPHA-IMINO ESTERS; HOMOALLYLIC AMINES; ACID-DERIVATIVES; HYDRAZONO ESTERS; ALLYLGLYCINE DERIVATIVES; AZIRIDINATION REACTION AB Chiral homo-allylic amines have been recognized in biologically active natural products and synthetic medicinal compounds. The most significant aspect of chiral homo-allylic amines relies on their synthetic versatility as chiral building blocks for the construction of a broad range of multi-functional organic compounds. A measure of the value of chiral homoallylic amines in organic synthesis is the large volume of work that has been devoted to their construction. Of the known asymmetric methods for their synthesis, the most popular method involves the formation of an imine followed by asymmetric allylation of the imine with reactive allylmetal reagents. An alternative approach is the metal-free asymmetric synthesis of chiral homo-allylic amines catalyzed by small organic molecules, which will be discussed in details in this review. C1 [Zhang, Quanxuan; Zhao, Wenjun] Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA. [Wang, Changning] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. RP Zhang, QX (reprint author), Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA. EM zhangquanxuan@gmail.com NR 66 TC 0 Z9 0 U1 2 U2 11 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-193X EI 1875-6298 J9 MINI-REV ORG CHEM JI Mini-Rev. Org. Chem. PY 2014 VL 11 IS 4 BP 508 EP 516 PG 9 WC Chemistry, Organic SC Chemistry GA AP8OP UT WOS:000342338600008 ER PT J AU Delori, FC Duncker, T Sparrow, JR AF Delori, Francois C. Duncker, Tobias Sparrow, Janet R. TI Quantitative Autofluorescence Imaging SO OPHTHALMOLOGICA LA English DT Meeting Abstract C1 [Delori, Francois C.] Harvard Univ, Mass Eye & Ear Infirm, Sch Med, Boston, MA USA. [Duncker, Tobias; Sparrow, Janet R.] Columbia Univ, New York, NY USA. EM francois_delori@meei.harvard.edu NR 4 TC 0 Z9 0 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3755 EI 1423-0267 J9 OPHTHALMOLOGICA JI Ophthalmologica PY 2014 VL 232 SU 1 BP 24 EP 25 PG 2 WC Ophthalmology SC Ophthalmology GA AP8WB UT WOS:000342358900028 ER PT J AU Maserejian, NN Shrader, P Trachtenberg, FL Hauser, R Bellinger, DC Tavares, M AF Maserejian, Nancy N. Shrader, Peter Trachtenberg, Felicia L. Hauser, Russ Bellinger, David C. Tavares, Mary TI Dental Sealants and Flowable Composite Restorations and Psychosocial, Neuropsychological, and Physical Development in Children SO PEDIATRIC DENTISTRY LA English DT Article DE COMPOSITE DENTAL RESIN; BISPHENOL A-GLYCIDYL METHACRYLATE; CHILD BEHAVIOR; EXECUTIVE FUNCTION; BODY COMPOSITION ID BISPHENOL-A CONCENTRATION; RANDOMIZED CLINICAL-TRIAL; BIS-GMA; AMALGAM TRIAL; LEACHED COMPONENTS; UNITED-STATES; RESIN; EXPOSURE; ASSOCIATION; FERTILITY AB Purpose: Dental sealant materials may intraorally release their components, including bisphenol-A (BPA), but long-term health effects are uncertain. The New England Children's Amalgam Trial (NECAT) found that composite restorations were associated with psychosocial, but not neuropsychological or physical, outcomes. The previous analysis did not consider sealants and preventive resin restorations (PRRs), which were routinely placed. The purpose of this analysis was to examine sealant/PRR exposure in association with psychosocial and other health outcomes. Methods: NECAT recruited 534 six- to 10-year-olds and provided dental care during a five-year follow-up. Annually, examiners conducted psychosocial and neuropsychological tests and measured body mass index (BMI) and fat percentage (BF%). Associations between surface years (SY) of sealants/PRRs and outcomes were tested using multivariable models. Results: Cumulative exposure level to sealants and/or PRRs was not associated with psychosocial assessments (eg, total problems: Child Behavior Checklist, 10-SY beta=-0.2 +/- 0.3,P=.60) or neuropsychological tests (eg, fullscale IQ, 10-SY beta=0.1 +/- 0.2, P=.60). There were no associations for changes in BMI-for-age z-score (P=.40), BF% (girls 10-SY beta=-0.2 +/- 03; boys 10-SY beta=0.1 +/- 03), or menarche (10-SY hazard ratio=0.91, 95% confidence interval=0.83-1.01, P=.08). Conclusions: This study showed no associations between exposure level of dental sealants or PRRs and behavioral, neuropsychological, or physical development in children over 5-years. C1 [Maserejian, Nancy N.] New England Res Inst, Dept Epidemiol, Watertown, MA 02172 USA. [Maserejian, Nancy N.] Harvard Univ, Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA 02115 USA. [Shrader, Peter; Trachtenberg, Felicia L.] New England Res Inst, Watertown, MA 02172 USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Sch Med, Boston, MA 02115 USA. [Hauser, Russ] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bellinger, David C.] Harvard Univ, Sch Publ Hlth, Boston Childrens Hospttal, Boston, MA 02115 USA. [Bellinger, David C.] Harvard Univ, Sch Med, Boston, MA USA. [Tavares, Mary] Harvard Univ, Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Adv Grad Educ Program Dent Publ Hlth, Boston, MA 02115 USA. [Tavares, Mary] Forsyth Inst, Cambridge, MA USA. RP Maserejian, NN (reprint author), New England Res Inst, Dept Epidemiol, 9 Galen St, Watertown, MA 02172 USA. EM nmaserej@psst.harvard.edu FU NIDCR NIH HHS [U01 DE011886]; NIEHS NIH HHS [R01 ES019155] NR 62 TC 6 Z9 6 U1 3 U2 9 PU AMER ACAD PEDIATRIC DENTISTRY PI CHICAGO PA 211 E CHICAGO AVENUE SUITE 1036, CHICAGO, IL 60611-2616 USA SN 0164-1263 EI 1942-5473 J9 PEDIATR DENT JI Pediatr. Dent. PD JAN-FEB PY 2014 VL 36 IS 1 BP 68 EP 75 PG 8 WC Dentistry, Oral Surgery & Medicine; Pediatrics SC Dentistry, Oral Surgery & Medicine; Pediatrics GA AP8NT UT WOS:000342336400012 PM 24717713 ER PT J AU Broyles, LM Binswanger, IA Jenkins, JA Finnell, DS Faseru, B Cavaiola, A Pugatch, M Gordon, AJ AF Broyles, Lauren M. Binswanger, Ingrid A. Jenkins, Jennifer A. Finnell, Deborah S. Faseru, Babalola Cavaiola, Alan Pugatch, Marianne Gordon, Adam J. TI Confronting Inadvertent Stigma and Pejorative Language in Addiction Scholarship: A Recognition and Response SO SUBSTANCE ABUSE LA English DT Editorial Material DE Criminal justice; language; mental disorders; publishing; social stigma; substance-related disorders AB Appropriate use of language in the field of addiction is important. Inappropriate use of language can negatively impact the way society perceives substance use and the people who are affected by it. Language frames what the public thinks about substance use and recovery, and it can also affect how individuals think about themselves and their own ability to change. But most importantly, language intentionally and unintentionally propagates stigma: the mark of dishonor, disgrace, and difference that depersonalizes people, depriving them of individual or personal qualities and personal identity. Stigma is harmful, distressing, and marginalizing to the individuals, groups, and populations who bear it. For these reasons, the Editorial Team of Substance Abuse seeks to formally operationalize respect for personhood in our mission, our public relations, and our instructions to authors. We ask authors, reviewers, and readers to carefully and intentionally consider the language used to describe alcohol and other drug use and disorders, the individuals affected by these conditions, and their related behaviors, comorbidities, treatment, and recovery in our publication. Specifically, we make an appeal for the use of language that (1) respects the worth and dignity of all persons ("people-first language"); (2) focuses on the medical nature of substance use disorders and treatment; (3) promotes the recovery process; and (4) avoids perpetuating negative stereotypes and biases through the use of slang and idioms. In this paper, we provide a brief overview of each of the above principles, along with examples, as well as some of the nuances and tensions that inherently arise as we give greater attention to the issue of how we talk and write about substance use and addiction. C1 [Broyles, Lauren M.; Jenkins, Jennifer A.; Gordon, Adam J.] VA Pittsburgh Healthcare Syst, CHERP, Pittsburgh, PA 15240 USA. [Broyles, Lauren M.; Gordon, Adam J.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA 15240 USA. [Broyles, Lauren M.; Gordon, Adam J.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Binswanger, Ingrid A.] Univ Colorado, Div Gen Internal Med, Sch Med, Aurora, CO USA. [Binswanger, Ingrid A.] Univ Colorado, Div Subst Dependence, Sch Med, Aurora, CO USA. [Binswanger, Ingrid A.] Denver Hlth Med Ctr, Community Hlth Serv, Denver, CO USA. [Finnell, Deborah S.] Johns Hopkins Univ, Sch Nursing, Acute & Chron Care Dept, Baltimore, MD USA. [Faseru, Babalola] Univ Kansas, Med Ctr, Dept Prevent Med & Publ Hlth, Kansas City, KS 66103 USA. [Faseru, Babalola] Univ Kansas, Med Ctr, Dept Family Med, Kansas City, KS 66103 USA. [Faseru, Babalola] Bur Hlth Promot, Kansas Dept Hlth & Environm, Topeka, KS USA. [Cavaiola, Alan] Monmouth Univ, West Long Branch, NJ USA. [Pugatch, Marianne] Boston Childrens Hosp, Adolescent Subst Abuse Program, Boston, MA USA. [Pugatch, Marianne] Boston Childrens Hosp, Ctr Subst Abuse Res, Boston, MA USA. [Pugatch, Marianne] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Pugatch, Marianne] Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA USA. RP Broyles, LM (reprint author), VA Pittsburgh Healthcare Syst, CHERP, Univ Dr C 151C, Pittsburgh, PA 15240 USA. EM Lauren.Broyles@va.gov RI Faseru, Babalola/N-6514-2014; OI Faseru, Babalola/0000-0003-3805-1850; Binswanger, Ingrid/0000-0001-8862-8078 FU NIAAA NIH HHS [T32 AA007567] NR 24 TC 21 Z9 21 U1 1 U2 14 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PY 2014 VL 35 IS 3 BP 217 EP 221 DI 10.1080/08897077.2014.930372 PG 5 WC Substance Abuse SC Substance Abuse GA AP7VA UT WOS:000342284200001 PM 24911031 ER PT J AU Gordon, AJ Galanter, M Khalsa, JH AF Gordon, Adam J. Galanter, Marc Khalsa, Jag H. TI Addressing Addiction Across Borders: An International Perspective on Policies, Scholarship, and Collaboration SO SUBSTANCE ABUSE LA English DT Editorial Material ID SUBSTANCE-ABUSE PREVENTION; SECONDARY-SCHOOL; STUDENTS; KHAT C1 [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Galanter, Marc] NYU, Sch Med, Div Alcoholism & Drug Abuse, New York, NY USA. [Khalsa, Jag H.] NIDA, Med Consequences Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. RP Gordon, AJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C,Bldg 30, Pittsburgh, PA 15240 USA. EM gordona@medschool.pitt.edu NR 18 TC 1 Z9 1 U1 1 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PY 2014 VL 35 IS 3 BP 290 EP 291 DI 10.1080/08897077.2014.929906 PG 2 WC Substance Abuse SC Substance Abuse GA AP7VA UT WOS:000342284200012 PM 24892635 ER PT J AU Bhattacharyya, S Cai, X Klein, JP AF Bhattacharyya, S. Cai, X. Klein, J. P. TI Dyscalculia, Dysgraphia, and Left-Right Confusion from a Left Posterior Peri-Insular Infarct SO BEHAVIOURAL NEUROLOGY LA English DT Article ID GERSTMANN-SYNDROME; SUBTRACTION; LANGUAGE; EPILEPSY; HUMANS; LOBE AB The Gerstmann syndrome of dyscalculia, dysgraphia, left-right confusion, and finger agnosia is generally attributed to lesions near the angular gyrus of the dominant hemisphere. A 68-year-old right-handed woman presented with sudden difficulty completing a Sudoku grid and was found to have dyscalculia, dysgraphia, and left-right confusion. Magnetic resonance imaging (MRI) showed a focus of abnormal reduced diffusivity in the left posterior insula and temporoparietal operculum consistent with acute infarct. Gerstmann syndrome from an insular or peri-insular lesion has not been described in the literature previously. Pathological and functional imaging studies show connections between left posterior insular region and inferior parietal lobe. We postulate that the insula and operculum lesion disrupted key functional networks resulting in a pseudoparietal presentation. C1 [Bhattacharyya, S.; Cai, X.; Klein, J. P.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Bhattacharyya, S.; Cai, X.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Bhattacharyya, S.; Cai, X.; Klein, J. P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Klein, J. P.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Bhattacharyya, S (reprint author), Brigham & Womens Hosp, Dept Neurol, 45 Francis St, Boston, MA 02115 USA. EM sbhattacharyya3@partners.org NR 17 TC 0 Z9 0 U1 4 U2 6 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 0953-4180 EI 1875-8584 J9 BEHAV NEUROL JI Behav. Neurol. PY 2014 AR 823591 DI 10.1155/2014/823591 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA AP3TO UT WOS:000342000800001 ER PT J AU Min, P Isaacs, S Parker, BA Thompson, PD Troyanos, C D'Hemecourt, P Dyer, S Baggish, AL Chan, SY AF Min, P. Isaacs, S. Parker, B. A. Thompson, P. D. Troyanos, C. D'Hemecourt, P. Dyer, S. Baggish, A. L. Chan, S. Y. TI INFLUENCE OF STATINS ON CIRCULATING MICRORNAS DURING PROLONGED AEROBIC EXERCISE SO CARDIOLOGY LA English DT Meeting Abstract C1 [Min, P.; Chan, S. Y.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. [Isaacs, S.; Baggish, A. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Performance Program, Boston, MA USA. [Isaacs, S.; Baggish, A. L.] Hartford Hosp, Div Cardiol, Hartford, CT 06115 USA. [Isaacs, S.; Baggish, A. L.] Boston Athlet Assoc, Boston, MA USA. [Isaacs, S.; Baggish, A. L.] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Cardiol Div,Dept Internal Med, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2014 VL 128 SU 1 MA 028 BP 43 EP 43 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AP2VI UT WOS:000341933400029 ER PT J AU Osborn, E AF Osborn, E. TI INTRAVASCULAR NEAR-INFRARED FLUORESCENCE MOLECULAR IMAGING OF INFLAMED PLAQUES SO CARDIOLOGY LA English DT Meeting Abstract C1 [Osborn, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2014 VL 128 SU 1 MA 127 BP 141 EP 141 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AP2VI UT WOS:000341933400127 ER PT J AU Shaikh, AY Maan, A Esa, N Kinno, M Floyd, KC Rosenthal, LS Browning, C McManus, DD AF Shaikh, A. Y. Maan, A. Esa, N. Kinno, M. Floyd, K. C. Rosenthal, L. S. Browning, C. McManus, D. D. TI MODIFIED HATCH SCORE PREDICTS 6-MONTH RECURRENCE OF ATRIAL FIBRILLATION AFTER PULMONARY VEIN ISOLATION: DATA FROM THE UNIVERSITY OF MASSACHUSETTS ATRIAL FIBRILLATION REGISTRY SO CARDIOLOGY LA English DT Meeting Abstract C1 [Shaikh, A. Y.; Esa, N.; Kinno, M.; Floyd, K. C.; Rosenthal, L. S.; Browning, C.; McManus, D. D.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [Maan, A.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Maan, A.] Harvard Univ, Sch Med, Boston, MA USA. [Floyd, K. C.; Rosenthal, L. S.; Browning, C.; McManus, D. D.] Univ Massachusetts, Sch Med, Div Cardiol & Electrophysiol, Worcester, MA USA. [McManus, D. D.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2014 VL 128 SU 1 MA 165 BP 179 EP 179 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AP2VI UT WOS:000341933400165 ER PT J AU Stefanescu, A Hsin, O Kamin, H Oglesbee, E Masek, B Liberthson, R Bhatt, A AF Stefanescu, A. Hsin, O. Kamin, H. Oglesbee, E. Masek, B. Liberthson, R. Bhatt, A. TI HEART: HELPING EMERGING ADULTS WITH CONGENITAL HEART DISEASE RECONCILE TRANSITION SO CARDIOLOGY LA English DT Meeting Abstract C1 [Stefanescu, A.; Hsin, O.; Kamin, H.; Oglesbee, E.; Masek, B.; Liberthson, R.; Bhatt, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2014 VL 128 SU 1 MA 180 BP 194 EP 194 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AP2VI UT WOS:000341933400180 ER PT J AU Shimada, YJ Passeri, JJ Baggish, AL O'Callaghan, C Lowry, PA Ghoshhajra, BB Ho, CY Januzzi, JL Seidman, CE Fifer, MA AF Shimada, Y. J. Passeri, J. J. Baggish, A. L. O'Callaghan, C. Lowry, P. A. Ghoshhajra, B. B. Ho, C. Y. Januzzi, J. L. Seidman, C. E. Fifer, M. A. TI REGRESSION OF HYPERTROPHY (AND FIBROSIS?) IN HYPERTROPHIC CARDIOMYOPATHY SO CARDIOLOGY LA English DT Meeting Abstract C1 [Passeri, J. J.; Baggish, A. L.; O'Callaghan, C.; Lowry, P. A.; Ghoshhajra, B. B.; Januzzi, J. L.; Fifer, M. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shimada, Y. J.; Ho, C. Y.; Seidman, C. E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Shimada, Y. J.; Passeri, J. J.; Baggish, A. L.; O'Callaghan, C.; Lowry, P. A.; Ghoshhajra, B. B.; Ho, C. Y.; Januzzi, J. L.; Seidman, C. E.; Fifer, M. A.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2014 VL 128 SU 1 MA 298 BP 312 EP 312 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AP2VI UT WOS:000341933400298 ER PT J AU Maan, A Mansour, M Ruskin, JN Heist, EK AF Maan, A. Mansour, M. Ruskin, J. N. Heist, E. K. TI IMPACT OF CATHETER ABLATION ON P-WAVE PARAMETERS ON 12-LEAD ELECTROCARDIOGRAM IN PATIENTS WITH ATRIAL FIBRILLATION SO CARDIOLOGY LA English DT Meeting Abstract C1 [Maan, A.; Mansour, M.; Ruskin, J. N.; Heist, E. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2014 VL 128 SU 1 MA 359 BP 373 EP 373 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AP2VI UT WOS:000341933400359 ER PT J AU Baggish, AL Park, J Min, PK Isaacs, S Parker, BA Thompson, PD Troyanos, C D'Hemecourt, P Dyer, S Thiel, M Hale, A Chan, SY AF Baggish, A. L. Park, J. Min, P-K. Isaacs, S. Parker, B. A. Thompson, P. D. Troyanos, C. D'Hemecourt, P. Dyer, S. Thiel, M. Hale, A. Chan, S. Y. TI RAPID UP-REGULATION AND CLEARANCE OF DISTINCT CIRCULATING MICRORNAS AFTER PROLONGED AEROBIC EXERCISE SO CARDIOLOGY LA English DT Meeting Abstract C1 [Baggish, A. L.; Isaacs, S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Performance Program, Boston, MA USA. [Park, J.; Min, P-K.; Thiel, M.; Hale, A.; Chan, S. Y.] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc Med, Dept Med,Med Sch, Boston, MA 02115 USA. [Parker, B. A.; Thompson, P. D.] Hartford Hosp, Div Cardiol, Hartford, CT 06115 USA. [Baggish, A. L.; Troyanos, C.; D'Hemecourt, P.; Dyer, S.] Boston Athlet Assoc, Boston, MA USA. [Min, P-K.] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Cardiol Div,Dept Internal Med, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2014 VL 128 SU 1 MA 426 BP 442 EP 442 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AP2VI UT WOS:000341933400428 ER PT J AU Zhang, XL Tian, YL Yuan, P Li, YY Yaseen, MA Grutzendler, J Moore, A Ran, CZ AF Zhang, Xueli Tian, Yanli Yuan, Peng Li, Yuyan Yaseen, Mohammad A. Grutzendler, Jaime Moore, Anna Ran, Chongzhao TI A bifunctional curcumin analogue for two-photon imaging and inhibiting crosslinking of amyloid beta in Alzheimer's disease SO CHEMICAL COMMUNICATIONS LA English DT Article ID IN-VIVO DETECTION; BRAIN; DEPOSITION; PROTEINS; BINDING; DESIGN; PROBES; CORTEX AB In this report, we designed a highly bright bifunctional curcumin analogue CRANAD-28. In vivo two-photon imaging suggested that CRANAD-28 could penetrate the blood brain barrier (BBB) and label plaques and cerebral amyloid angiopathies (CAAs). We also demonstrated that this imaging probe could inhibit the crosslinking of amyloid beta induced either by copper or by natural conditions. C1 [Zhang, Xueli; Tian, Yanli; Li, Yuyan; Yaseen, Mohammad A.; Moore, Anna; Ran, Chongzhao] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Imaging Lab,AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Zhang, Xueli; Li, Yuyan] China Pharmaceut Univ, Sch Pharm, Nanjing, Jiangsu, Peoples R China. [Tian, Yanli] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Parasitol, Guangzhou 510275, Guangdong, Peoples R China. [Yuan, Peng; Grutzendler, Jaime] Yale Univ, Dept Neurol, New Haven, CT USA. RP Moore, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Imaging Lab,AA Martinos Ctr Biomed Imaging, Bldg 75, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu; cran@nmr.mgh.harvard.edu RI Yuan, Peng/P-3244-2016 OI Yuan, Peng/0000-0003-4051-4447 FU [K25AG036760]; [K99AG042026] FX This work was supported by the K25AG036760 award to C.R. and the K99AG042026 award to M.A.Y. The authors would also like to thank Pamela Pantazopoulos, B.S. for proofreading this manuscript. NR 40 TC 17 Z9 17 U1 11 U2 46 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 EI 1364-548X J9 CHEM COMMUN JI Chem. Commun. PY 2014 VL 50 IS 78 BP 11550 EP 11553 DI 10.1039/c4cc03731f PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA AP0SL UT WOS:000341774200030 PM 25134928 ER PT J AU Horner, MD VanKirk, KK Dismuke, CE Turner, TH Muzzy, W AF Horner, Michael David VanKirk, Kathryn K. Dismuke, Clara E. Turner, Travis H. Muzzy, Wendy TI Inadequate Effort on Neuropsychological Evaluation is Associated With Increased Healthcare Utilization SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Health care utilization; Neuropsychological assessment; Clinical neuropsychology; Health outcomes; Effort ID EXAGGERATION; VETERANS; SAMPLE; RATES AB Patients who exert inadequate effort on neuropsychological examination might not receive accurate diagnoses and recommendations, and might not cooperate fully with other aspects of healthcare. This study examined whether inadequate effort is associated with increased healthcare utilization. Of 355 patients seen for routine, clinical neuropsychological examination at a VA Medical Center, 283 (79.7%) showed adequate effort and 72 (20.3%) showed inadequate effort, as determined at time of evaluation using the Word Memory Test and/or Test of Memory Malingering. Utilization data included number of Emergency Department (ED) visits and inpatient hospitalizations in the year following evaluation. Patients who had shown inadequate effort on examination had more Emergency Department visits, more inpatient hospitalizations, and more days of inpatient hospitalization in the year after evaluation, compared to patients who had exerted adequate effort. This finding was not attributable to group differences in age or medical/psychiatric comorbidities. Thus, patients who exerted inadequate effort showed greater healthcare utilization in the year following evaluation. Such patients might use more resources since diagnostic evaluations are inconclusive. Inadequate effort on examination might also serve as a "marker" for more general failure to cooperate fully in one's healthcare, possibly resulting in greater utilization. C1 [Horner, Michael David; VanKirk, Kathryn K.; Turner, Travis H.] Ralph H Johnson Dept Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC 29401 USA. [Horner, Michael David; VanKirk, Kathryn K.; Turner, Travis H.; Muzzy, Wendy] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Dismuke, Clara E.] Ralph H Johnson Dept Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC 29401 USA. [Dismuke, Clara E.] Med Univ S Carolina, Dept Internal Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Turner, Travis H.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Muzzy, Wendy] Charleston Res Inst, Charleston, SC USA. RP Horner, MD (reprint author), Ralph H Johnson Dept Vet Affairs Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM hornermd@musc.edu FU American Academy of Clinical Neuropsychology Foundation FX This work was supported by a grant from the American Academy of Clinical Neuropsychology Foundation to Dr. VanKirk. NR 14 TC 5 Z9 5 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1385-4046 EI 1744-4144 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PY 2014 VL 28 IS 5 BP 703 EP 713 DI 10.1080/13854046.2014.925143 PG 11 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA AP4MM UT WOS:000342051100001 PM 24931877 ER PT J AU Papp, KV Amariglio, RE Dekhtyar, M Roy, K Wigman, S Bamfo, R Sherman, J Sperling, RA Rentz, DM AF Papp, Kathryn V. Amariglio, Rebecca E. Dekhtyar, Maria Roy, Kamolika Wigman, Sarah Bamfo, Rose Sherman, Julia Sperling, Reisa A. Rentz, Dorene M. TI Development of a Psychometrically Equivalent Short Form of the Face-Name Associative Memory Exam for use Along the Early Alzheimer's Disease Trajectory SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Associative memory; Preclinical Alzheimer's disease; Mild Cognitive Impairment; Neuropsychology; Test development ID MILD COGNITIVE IMPAIRMENT; SEMANTIC MEMORY; AMYLOID DEPOSITION; DEMENTIA; DEFICITS; PERFORMANCE; DECLINE AB Neuropsychologists are developing more challenging and specific tests to detect early and subtle changes in cognition related to preclinical Alzheimer's disease (AD). The 16-item Face-Name Associative Memory Exam (FNAME-16) is a challenging paired associative memory test able to detect subtle memory changes associated with biomarker evidence of preclinical AD. However, as individuals progress along the AD trajectory, measures that are sensitive at the preclinical stage may become too challenging by the stage of Mild Cognitive Impairment (MCI). Our goal was to develop a modified version of the face-name and face-occupation paired associative memory task (FNAME-12) with fewer stimuli and additional learning trials suitable for use in MCI. We administered the FNAME-12A, an alternate version FNAME 12B, the original FNAME-16, and a series of other neuropsychological measures to 65 clinically normal (CN) older adults (aged 65 to 85) and a subsample characterized by MCI (n = 18). The FNAME-12 exhibited psychometric equivalence with the FNAME-16 (r = .77, p < .001) and was correlated with other measures of episodic and semantic memory. The alternate form, FNAME-12B, was highly correlated with FNAME-12A (r = .76, p < .001). Mean performance on the FNAME 12A, stratified by education, was generated. The task could be completed by our MCI group yet remained challenging in the CN group, providing evidence for its utility along the AD trajectory. C1 [Papp, Kathryn V.; Amariglio, Rebecca E.; Dekhtyar, Maria; Roy, Kamolika; Wigman, Sarah; Sherman, Julia; Sperling, Reisa A.; Rentz, Dorene M.] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Papp, Kathryn V.; Amariglio, Rebecca E.; Sperling, Reisa A.; Rentz, Dorene M.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Wigman, Sarah; Sperling, Reisa A.; Rentz, Dorene M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Bamfo, Rose] Harvard Univ, Dept Neurobiol, Cambridge, MA USA. [Sperling, Reisa A.; Rentz, Dorene M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Papp, KV (reprint author), Ctr Alzheimer Res & Treatment, 221 Longwood Ave BL 104, Boston, MA 02115 USA. EM katepapp@partners.org FU NIH [P01AG036694, P50AG005134]; NIA grants [5T32AG023480, 5R01AG027435]; Alzheimer's Association [SG COG-13-282201] FX This work was supported by the NIH grants P01AG036694, P50AG005134, NIA grants 5T32AG023480 and 5R01AG027435 and the Alzheimer's Association SG COG-13-282201. NR 33 TC 2 Z9 2 U1 0 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1385-4046 EI 1744-4144 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PY 2014 VL 28 IS 5 BP 771 EP 785 DI 10.1080/13854046.2014.911351 PG 15 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA AP4MM UT WOS:000342051100006 PM 24815535 ER PT J AU Clark, AL Amick, MM Fortier, C Milberg, WP McGlinchey, RE AF Clark, Alexandra L. Amick, Melissa M. Fortier, Catherine Milberg, William P. McGlinchey, Regina E. TI Poor Performance Validity Predicts Clinical Characteristics and Cognitive Test Performance of OEF/OIF/OND Veterans in a Research Setting SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Symptom validity; Effort testing; Symptom exaggeration; Deployment ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; MALINGERED NEUROCOGNITIVE DYSFUNCTION; NEUROPSYCHOLOGICAL TEST-PERFORMANCE; WORD MEMORY TEST; PERSONALITY-ASSESSMENT INVENTORY; TEST-RETEST RELIABILITY; SYMPTOM VALIDITY; HEAD-INJURY; EVALUATION CONTEXT AB This study examined the performance of 198 Veteran research participants deployed during Operation Enduring Freedom, Operation Iraqi Freedom, and/or Operation New Dawn (OEF/OIF/OND) on four measures of performance validity: the Medical Symptom Validity Test (MSVT), California Verbal Learning Test: Forced Choice Recognition (FCR), Reliable Digit Span (RDS), and TOVA Symptom Exaggeration Index (SEI). Failure on these performance validity tests (PVTs) ranged from 4% to 9%. The overall base rate of poor performance validity, as measured by failure of the MSVT in conjunction with an embedded PVT (FCR, RDS, SEI), was 5.6%. Regression analyses revealed that poor performance validity predicted cognitive test performance and self-reported psychological symptom severity. Furthermore, a greater prevalence of traumatic brain injury (TBI), Post-Traumatic Stress Disorder (PTSD), co-morbid TBI/PTSD, and other Axis I diagnoses, was observed among participants with poor effort. Although poor performance validity is relatively uncommon in a research setting, these findings demonstrate that clinicians should be cautious when interpreting psychological symptoms and neuropsychological test performance of Veteran participants who fail effort measures. C1 [Clark, Alexandra L.; Amick, Melissa M.; Fortier, Catherine; Milberg, William P.; McGlinchey, Regina E.] VA Boston Healthcare Syst, Translat Res Ctr TBI & Stress Disorders TRACTS, Boston, MA 02130 USA. [Clark, Alexandra L.; Amick, Melissa M.; Fortier, Catherine; Milberg, William P.; McGlinchey, Regina E.] VA Boston Healthcare Syst, GRECC, Boston, MA 02130 USA. [Fortier, Catherine; Milberg, William P.; McGlinchey, Regina E.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Amick, Melissa M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Amick, MM (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave, Boston, MA 02130 USA. EM Melissa.Amick@va.gov RI McGlinchey, Regina/R-1971-2016 FU Translational Research Center for TBI and Stress Disorders (TRACTS) VA Rehabilitation Research and Development Center Grant [B6796-C] FX This work was supported by the Translational Research Center for TBI and Stress Disorders (TRACTS) VA Rehabilitation Research and Development Center Grant [B6796-C] awarded to Dr. Regina McGlinchey. NR 99 TC 10 Z9 10 U1 6 U2 13 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1385-4046 EI 1744-4144 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PY 2014 VL 28 IS 5 BP 802 EP 825 DI 10.1080/13854046.2014.904928 PG 24 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA AP4MM UT WOS:000342051100008 PM 24766521 ER PT J AU Cottingham, ME Victor, TL Boone, KB Ziegler, EA Zeller, M AF Cottingham, Maria Easter Victor, Tara L. Boone, Kyle B. Ziegler, Elizabeth A. Zeller, Michelle TI Apparent Effect of Type of Compensation Seeking (Disability Versus Litigation) on Performance Validity Test Scores may be due to Other Factors SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Compensation; Performance validity; Neuropsychology; Disability; mTBI ID SOCIAL-SECURITY DISABILITY; TRAUMATIC BRAIN-INJURY; WORD RECOGNITION TEST; MILD HEAD TRAUMA; SUSPECT EFFORT; RESPONSE BIAS; SYMPTOM EXAGGERATION; CONSULTATIVE EXAM; CROSS-VALIDATION; BASE RATES AB Neuropsychologists use performance validity tests (PVTs; Larrabee, 2012) to ensure that results of testing are reflective of the test taker's true neurocognitive ability, and their use is recommended in all compensation-seeking settings. However, whether the type of compensation context (e.g., personal injury litigation versus disability seeking) impacts the nature and extent of neurocognitive symptom feigning has not been adequately investigated. PVT performance was compared in an archival data set of noncredible individuals in either a personal injury litigation (n = 163) or a disability-seeking context (n = 201). Individuals were deemed noncredible based on meeting Slick, Sherman, and Iverson's (1999) criteria including failure on at least two PVTs and a lack of congruency between their low cognitive scores and normal function in activities of daily living (ADLs). In general, disability seekers tended to perform in a less sophisticated manner than did litigants (i.e., they failed more indicators and did so more extensively). Upon further investigation, these differences were in part accounted for by type of diagnoses feigned; those seeking compensation for mental health diagnoses were more likely to feign or exaggerate a wide variety of cognitive deficits, whereas those with claimed medical diagnoses (i.e., traumatic brain injury) were more targeted in their attempts to feign and/or exaggerate neurocognitive compromise. C1 [Cottingham, Maria Easter] Olive View UCLA Med Ctr, Dept Psychiat, Sylmar, CA 91342 USA. [Victor, Tara L.] Calif State Univ, Dept Psychol, Carson, CA USA. [Boone, Kyle B.] Alliant Int Univ, Calif Sch Forens Studies, Los Angeles, CA USA. [Ziegler, Elizabeth A.] Spokane Vet Adm Med Ctr, Dept Mental Behav Hlth, Spokane, WA USA. [Zeller, Michelle] Greater Los Angeles Vet Healthcare Syst, Dept Psychol, Los Angeles, CA USA. RP Cottingham, ME (reprint author), TBI Clin, 11050 Mt Belvedere Blvd,Bldg 25, Ft Drum, NY 13601 USA. EM mecottingham@gmail.com NR 51 TC 6 Z9 6 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1385-4046 EI 1744-4144 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PY 2014 VL 28 IS 6 BP 1030 EP 1047 DI 10.1080/13854046.2014.951397 PG 18 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA AP4MR UT WOS:000342051600010 PM 25157537 ER PT J AU Zoller, AS Gaal, IM Royer, CA Locascio, JJ Amariglio, RE Blacker, D Okereke, OI Johnson, KA Sperling, RA Rentz, DM Marshall, GA AF Zoller, Amy S. Gaal, Ildiko M. Royer, Christine A. Locascio, Joseph J. Amariglio, Rebecca E. Blacker, Deborah Okereke, Olivia I. Johnson, Keith A. Sperling, Reisa A. Rentz, Dorene M. Marshall, Gad A. TI SIST-M-IR Activities of Daily Living Items that Best Discriminate Clinically Normal Elderly from those with Mild Cognitive Impairment SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Activities of daily living; Alzheimer's disease; clinical assessment; clinically normal elderly; daily functioning; mild cognitive impairment ID ALZHEIMERS ASSOCIATION WORKGROUPS; INSTRUMENTAL ACTIVITIES; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; EVERYDAY FUNCTION; DISEASE SPECTRUM; DEMENTIA; RECOMMENDATIONS; VALIDATION; COMMUNITY AB Background: Activities of daily living (ADL) impairment is a hallmark of Alzheimer's disease (AD) dementia, but impairment in instrumental ADL (IADL) has been reported in mild cognitive impairment (MCI). The Structured Interview and Scoring Tool-Massachusetts Alzheimer's Disease Research Center (MADRC)-Informant Report (SIST-M-IR) includes 60 graded items that assist in scoring the Clinical Dementia Rating; it assesses the spectrum of cognitive and ADL changes relevant to early AD. Of the 60 SIST-M-IR items, 41 address IADL; we aimed to determine which of these best discriminate individuals with MCI from clinically normal (CN) elderly. Methods: We assessed 447 subjects participating in the MADRC longitudinal cohort (289 CN, 158 MCI). We performed logistic regression analyses predicting the probability of CN vs. MCI diagnosis using the SIST-M-IR items. Analyses were adjusted for demographic characteristics. Results: We found that 4 SIST-M-IR items best discriminated between CN and MCI subjects (MCI performing worse than CN): "participating in games that involve retrieving words" (p=0.0001), "navigating to unfamiliar areas" (p=0.001), "performing mental tasks involved in a former primary job" (p=0.002), and "fixing things or finishing projects" (p=0.002). Conclusions: Our results point to the earliest functional changes seen in elderly at risk for AD, which could be captured by a few simple questions. Honing the sensitivity of clinical assessment tools will help clinicians differentiate those individuals with normal aging from those who are developing cognitive impairment. C1 [Zoller, Amy S.; Blacker, Deborah; Okereke, Olivia I.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Locascio, Joseph J.; Amariglio, Rebecca E.; Sperling, Reisa A.; Rentz, Dorene M.; Marshall, Gad A.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Johnson, Keith A.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zoller, Amy S.; Locascio, Joseph J.; Blacker, Deborah; Okereke, Olivia I.; Johnson, Keith A.; Sperling, Reisa A.; Rentz, Dorene M.; Marshall, Gad A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA. [Gaal, Ildiko M.] Wellesley Coll, Wellesley, MA 02481 USA. [Royer, Christine A.] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20037 USA. [Amariglio, Rebecca E.; Johnson, Keith A.; Sperling, Reisa A.; Rentz, Dorene M.; Marshall, Gad A.] Harvard Univ, Sch Med, Ctr Alzheimer Res & Treatment, Brigham & Womens Hosp, Boston, MA 02115 USA. [Amariglio, Rebecca E.; Johnson, Keith A.; Sperling, Reisa A.; Rentz, Dorene M.; Marshall, Gad A.] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Amariglio, Rebecca E.; Okereke, Olivia I.; Rentz, Dorene M.] Harvard Univ, Sch Med, Dept Psychiat, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Marshall, GA (reprint author), Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, 221 Longwood Ave,BL-104H, Boston, MA 02115 USA. EM gamarshall@partners.org RI Okereke, Olivia/R-9934-2016 FU Harvard NeuroDiscovery Center; Massachusetts Alzheimer's Disease Research Center [P50 AG005134, K23 AG033634, K24 AG035007, R01 AG027435]; Harvard Aging Brain Study [P01 AGO36694, R01 AG037497] FX This study was supported by the Harvard NeuroDiscovery Center clinical research pilot study grant, the Massachusetts Alzheimer's Disease Research Center (P50 AG005134), K23 AG033634, K24 AG035007, R01 AG027435, and the Harvard Aging Brain Study (P01 AGO36694, R01 AG037497). NR 33 TC 2 Z9 2 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 EI 1875-5828 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PY 2014 VL 11 IS 8 BP 785 EP 791 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AP5TW UT WOS:000342142600007 PM 25212917 ER PT J AU Lee, J Ryu, H Keum, G Yoon, YJ Kowall, NW Ryu, H AF Lee, J. Ryu, H. Keum, G. Yoon, Y. J. Kowall, N. W. Ryu, H. TI Therapeutic Targeting of Epigenetic Components in Amyotrophic Lateral Sclerosis (ALS) SO CURRENT MEDICINAL CHEMISTRY LA English DT Article DE Amyotrophic lateral sclerosis; epigenetic components; HDAC inhibitor; motor neuron; transcription; therapeutics ID HISTONE DEACETYLASE INHIBITORS; SPINAL MUSCULAR-ATROPHY; L-ALANINE BMAA; MOUSE MODEL; HUNTINGTONS-DISEASE; PROLONGS SURVIVAL; SODIUM PHENYLBUTYRATE; SUPEROXIDE-DISMUTASE; VALPROIC ACID; LINKED SOD1 AB Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron disease characterized by degeneration of motor neuron and glial activation followed by the progressive muscle loss and paralysis. Numerous distinct therapeutic interventions have been examined but currently ALS does not have a cure or an efficacious treatment for the disorder. Glutamate-induced excitotoxicity, inflammation, mitochondrial dysfunction, oxidative stress, protein aggregation, transcription deregulation, and epigenetic modifications are associated with the pathogenesis of ALS and known to be therapeutic targets in ALS. In this review, we discuss translational pharmacological studies targeting epigenetic components to ameliorate ALS. Understanding of the epigenetic mechanisms will provide novel insights that will further identify potential biological markers and therapeutic approaches for treating ALS. A combination of treatments that modulate epigenetic components and multiple targets may prove to be the most effective therapy for ALS. C1 [Lee, J.; Kowall, N. W.; Ryu, H.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Lee, J.; Ryu, H.; Kowall, N. W.; Ryu, H.] Boston Univ, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Lee, J.; Ryu, H.; Kowall, N. W.; Ryu, H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Keum, G.; Yoon, Y. J.; Ryu, H.] Korea Inst Sci & Technol, Ctr Neuromed, Brain Sci Inst, Seoul 110799, South Korea. RP Lee, J (reprint author), Boston Univ, Sch Med, VA Boston Healthcare Syst, 150 South Huntington Ave, Boston, MA 02130 USA. EM junghee@bu.edu; hoonryu@bu.edu RI Keum, Gyochang/E-7492-2013; Kowall, Neil/G-6364-2012 OI Keum, Gyochang/0000-0001-8767-8022; Kowall, Neil/0000-0002-6624-0213 FU VA Merit Award; NIH [NS067283]; KIST [2E24380] FX We thank Yu Jin Hwang for the preparation of manuscript. This study was supported by VA Merit Award (J.L. and N.W.K.) and, in part, by NIH NS067283 (H.R.). This study was also supported by Flagship Grant (2E24380) (H.R.) from KIST. NR 77 TC 1 Z9 1 U1 1 U2 13 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 EI 1875-533X J9 CURR MED CHEM JI Curr. Med. Chem. PY 2014 VL 21 IS 31 BP 3576 EP 3582 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA AP3IU UT WOS:000341969600005 PM 25005187 ER PT J AU Henry, RR Holman, RR Giugliano, RP Raal, FJ Sullivan, D Honarpour, N Nelson, P Elliott, M Liu, T Wasserman, SM Somaratne, R Koren, MJ AF Henry, R. R. Holman, R. R. Giugliano, R. P. Raal, F. J. Sullivan, D. Honarpour, N. Nelson, P. Elliott, M. Liu, T. Wasserman, S. M. Somaratne, R. Koren, M. J. TI Effects of Long-term, Monthly Administration of the Pcsk9 Inhibitor Evolocumab (Amg 145) in Patients with Dysglycemia or Metabolic Syndrome SO JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS LA English DT Meeting Abstract C1 [Henry, R. R.] VA San Diego Healthcare Syst, Ctr Metab Res, San Diego, CA USA. [Henry, R. R.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Holman, R. R.] Univ Oxford, OCDEM, Diabete Trials Unit, Oxford OX1 2JD, England. [Giugliano, R. P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Raal, F. J.] Univ Witwatersrand, Carbohydrate & Lipid Metab Res Unit, Johannesburg, South Africa. [Sullivan, D.] Royal Prince Alfred Hosp, Dept Clin Biochem, Camperdown, NSW 2050, Australia. [Honarpour, N.; Nelson, P.; Liu, T.; Wasserman, S. M.; Somaratne, R.] Amgen Inc, Thousand Oaks, CA USA. [Elliott, M.] Amgen Ltd, Cambridge, MA USA. [Koren, M. J.] Jacksonville Ctr Clin Res, Jacksonville, FL USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU JAPAN ATHEROSCLEROSIS SOC PI TOKYO PA NICHINAI-KAIKAN B1, 3-28-8 HONGO BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 1340-3478 EI 1880-3873 J9 J ATHEROSCLER THROMB JI J. Atheroscler. Thromb. PY 2014 VL 21 SU 3 MA Ab115 BP S8 EP S8 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AP4TK UT WOS:000342071500017 ER PT S AU Loftis, JM Janowsky, A AF Loftis, Jennifer M. Janowsky, Aaron BE Cui, C Shurtleff, D Harris, RA TI Neuroimmune Basis of Methamphetamine Toxicity SO NEUROIMMUNE SIGNALING IN DRUG ACTIONS AND ADDICTIONS SE International Review of Neurobiology LA English DT Review; Book Chapter ID BLOOD-BRAIN-BARRIER; HEPATITIS-C VIRUS; NF-KAPPA-B; SUBSTANCE USE DISORDERS; NECROSIS-FACTOR-ALPHA; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; TIGHT JUNCTION PROTEINS; MATURE DENDRITIC CELLS; DOPAMINE NERVE-ENDINGS; INDUCED NEUROTOXICITY AB Although it is not known which antigen-specific immune responses (or if antigen-specific immune responses) are relevant or required for methamphetamine's neurotoxic effects, it is apparent that methamphetamine exposure is associated with significant effects on adaptive and innate immunity. Alterations in lymphocyte activity and number, changes in cytokine signaling, impairments in phagocytic functions, and glial activation and gliosis have all been reported. These drug-induced changes in immune response, particularly within the CNS, are now thought to play a critical role in the addiction process for methamphetamine dependence as well as for other substance use disorders. In Section 2, methamphetamine's effects on glial cell (e.g., microglia and astrocytes) activity and inflammatory signaling cascades are summarized, including how alterations in immune cell function can induce the neurotoxic and addictive effects of methamphetamine. Section 2 also describes neurotransmitter involvement in the modulation of methamphetamine's inflammatory effects. Section 3 discusses the very recent use of pharmacological and genetic animal models which have helped elucidate the behavioral effects of methamphetamine's neurotoxic effects and the role of the immune system. Section 4 is focused on the effects of methamphetamine on blood brain barrier integrity and associated immune consequences. Clinical considerations such as the combined effects of methamphetamine and HIV and/or HCV on brain structure and function are included in Section 4. Finally, in Section 5, immune-based treatment strategies are reviewed, with a focus on vaccine development, neuroimmune therapies, and other anti-inflammatory approaches. C1 [Loftis, Jennifer M.; Janowsky, Aaron] Portland VA Med Ctr, Res & Dev Serv, Portland, OR 97239 USA. [Loftis, Jennifer M.; Janowsky, Aaron] Oregon Hlth & Sci Univ, Dept Psychiat, Sch Med, Portland, OR 97201 USA. [Loftis, Jennifer M.; Janowsky, Aaron] Oregon Hlth & Sci Univ, Methamphetamine Abuse Res Ctr, Portland, OR 97201 USA. [Janowsky, Aaron] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. RP Loftis, JM (reprint author), Portland VA Med Ctr, Res & Dev Serv, Portland, OR 97239 USA. EM loftisj@ohsu.edu FU BLRD VA [I01 BX002061]; NIDA NIH HHS [P50 DA018165, DA018165] NR 153 TC 17 Z9 17 U1 5 U2 11 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 978-0-12-801284-0 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 2014 VL 118 BP 165 EP 197 DI 10.1016/B978-0-12-801284-0.00007-5 PG 33 WC Neurosciences SC Neurosciences & Neurology GA BB2IQ UT WOS:000341798700007 PM 25175865 ER PT J AU Beca, F Santos, R Vieira, D Zeferino, L Dufloth, R Schmitt, F AF Beca, Francisco Santos, Renata Vieira, Daniella Zeferino, Luiz Dufloth, Rozany Schmitt, Fernando TI Primary relapse site pattern in women with triple-negative breast cancer SO PATHOLOGY RESEARCH AND PRACTICE LA English DT Article DE Breast cancer; Triple-negative; Recurrence; Relapse; Metastasis ID BASAL-LIKE PHENOTYPE; CLINICOPATHOLOGICAL FEATURES; DISTANT METASTASES; CARCINOMA; EXPRESSION; RECURRENCE; SUBTYPES; TUMORS; BONE; SURVIVAL AB Despite the remarkable improvements in breast cancer (BC) characterization, accurate prediction of BC clinical behavior is often still difficult to achieve. Some studies have investigated the association between the molecular subtype, namely the basal-like BC and the pattern of relapse, however only few investigated the association between relapse pattern and immunohistochemical defined triple-negative breast cancers (TNBCs). The aim of this study was to evaluate the pattern of relapse in patients with TNBC, namely the primary distant relapse site: One-hundred twenty nine (129) invasive breast carcinomas with follow-up information were classified according to the molecular subtype using immunohistochemistry for ER, PgR and Her2. The association between TNBC and distant relapse primary site was analyzed by logistic regression. Using multivariate logistic regression analysis patients with TNBC displayed only 0.09(95% CI: 0.00-0.74; p = 0.02) the odds of, the non-TNBC patients of developing bone primary relapse. Regarding visceral and lymph-node relapse, no differences between in this cohort were found. Though classically regarded as aggressive tumors, TNBCs rarely development primary relapse in bone when compared to non-TNBC, a clinical relevant fact when investigating a metastasis of an occult or non-sampled primary BC. (C) 2014 Elsevier GmbH. All rights reserved. C1 [Beca, Francisco; Schmitt, Fernando] Univ Porto, IPATIMUP Inst Mol Pathol & Immunol, P-4100 Oporto, Portugal. [Beca, Francisco] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Santos, Renata] Univ Fed Santa Catarina, Fac Med, Florianopolis, SC, Brazil. [Vieira, Daniella] Univ Fed Santa Catarina, Dept Pathol, Fac Med, Florianopolis, SC, Brazil. [Zeferino, Luiz] State Univ Campinas UNICAMP, Dept Obstet & Gynaecol, Sch Med Sci, Campinas, SP, Brazil. [Dufloth, Rozany] Sao Paulo State Univ UNESP, Dept Pathol, Fac Med Botucatu, Botucatu, SP, Brazil. [Schmitt, Fernando] Univ Toronto, Dept Lab Med & Pathobiol, Fac Med, Univ Hlth Network, Toronto, ON M5G 2C4, Canada. RP Schmitt, F (reprint author), Univ Toronto, Dept Lab Med & Pathobiol, Fac Med, Univ Hlth Network,Toronto Gen Hosp, 200 Elizabeth St,11E-215B, Toronto, ON M5G 2C4, Canada. EM fernando.schmitt@uhn.ca OI Schmitt, Fernando/0000-0002-3711-8681; Beca, Francisco/0000-0002-4409-012X FU FCT (Fundacao para a Ciencia e Tecnologia) [HMSP-ICJ/0006/2012] FX IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and is partially supported by FCT (Fundacao para a Ciencia e Tecnologia). Although this work did not receive any specific funding, by time of the completion and submission of the manuscript, Francisco F. de Beca was supported by the FCT grant (HMSP-ICJ/0006/2012) and was affiliated with the Department of Medical Oncology, Dana-Farber Cancer Institute/Harvard Medical School, Boston, MA, USA. NR 34 TC 4 Z9 4 U1 0 U2 5 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0344-0338 J9 PATHOL RES PRACT JI Pathol. Res. Pract. PY 2014 VL 210 IS 9 BP 571 EP 575 DI 10.1016/j.prp.2014.05.011 PG 5 WC Pathology SC Pathology GA AP7HB UT WOS:000342247300006 PM 24939141 ER PT S AU Favreau, JT Ott, HC Gaudette, GR AF Favreau, J. T. Ott, H. C. Gaudette, G. R. BE Li, RK Weisel, RD TI Cardiac biomechanics and heart dysfunction SO CARDIAC REGENERATION AND REPAIR, VOL 1: PATHOLOGY AND THERAPIES SE Woodhead Publishing Series in Biomaterials LA English DT Article; Book Chapter DE magnetic resonance imaging; echocardiography; sonomicrometry; regional mechanical function; global mechanical function; ejection fraction; stroke volume; stroke work; regional stroke work; active contractile properties; passive mechanical properties ID RECRUITABLE STROKE WORK; VENTRICULAR-FUNCTION; PHASE CORRELATION; ECHOCARDIOGRAPHY; MECHANICS; VOLUME; SONOMICROMETRY; VALIDATION; PRESSURE; STRAIN AB Infarction and ischemia in the heart directly result in death of cardiac muscle cells and can significantly reduce mechanical function in the heart, both regionally and globally. The overall goal of cardiac therapies is to return myocardial function to its healthy state. To understand the effects of ischemia and infarction, it is necessary to develop reproducible methods to quantify regional cardiac function. Early-stage cell treatments may be unable to return global function to its healthy state, so it is also necessary to quantify cardiac function on a regional basis. In this chapter, we discuss the many parameters used to quantify cardiac function, how the parameters are assessed, and how they change during cardiac ischemia and infarction. C1 [Favreau, J. T.; Gaudette, G. R.] Worcester Polytech Inst, Dept Biomed Engn, Worcester, MA 01609 USA. [Ott, H. C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Gaudette, GR (reprint author), Worcester Polytech Inst, Dept Biomed Engn, 100 Inst Rd, Worcester, MA 01609 USA. EM gaudette@wpi.edu NR 23 TC 0 Z9 0 U1 0 U2 2 PU WOODHEAD PUBL LTD PI CAMBRIDGE PA ABINGTON HALL ABINGTON, CAMBRIDGE CB1 6AH, CAMBS, ENGLAND SN 2049-9485 BN 978-0-85709-670-8; 978-0-85709-658-6 J9 WOODH PUBL SER BIOM PY 2014 VL 71 BP 27 EP 40 DI 10.1533/9780857096708.1.27 PG 14 WC Cell & Tissue Engineering; Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cell Biology; Cardiovascular System & Cardiology; Engineering GA BB2DQ UT WOS:000341698900004 ER PT B AU Deckersbach, T Hansen, N Holzel, B AF Deckersbach, Thilo Hansen, Natasha Holzel, Britta BE Baer, RA TI Mindfulness-Based Cognitive Therapy for Bipolar Disorder SO MINDFULNESS-BASED TREATMENT APPROACHES: CLINICIAN'S GUIDE TO EVIDENCE BASE AND APPLICATIONS, 2ND EDITION SE Practical Resources for the Mental Health Professional LA English DT Article; Book Chapter ID TREATMENT ENHANCEMENT PROGRAM; RANDOMIZED CONTROLLED-TRIAL; BEHAVIORAL-APPROACH SYSTEM; MAJOR DEPRESSIVE DISORDER; WEEKLY SYMPTOMATIC STATUS; SOCIAL RHYTHM THERAPY; LIFE EVENTS; SPECTRUM DISORDERS; STEP-BD; I-DISORDER C1 [Deckersbach, Thilo] Massachusetts Gen Hosp, Dept Psychiat, Bipolar Clin, Boston, MA 02114 USA. [Hansen, Natasha] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. [Holzel, Britta] Charite, Inst Med Psychol, Berlin, Germany. RP Deckersbach, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bipolar Clin, Boston, MA 02114 USA. RI Lazar, Sara/G-3809-2012 OI Lazar, Sara/0000-0003-1126-8363 NR 89 TC 8 Z9 8 U1 2 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-391452-1; 978-0-12-416031-6 J9 PRACT RESOUR MENT PY 2014 BP 77 EP 94 DI 10.1016/B978-0-12-416031-6.00004-9 PG 18 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BB2CQ UT WOS:000341648300005 ER PT J AU Medarova, Z Ghosh, SK Vangel, M Drake, R Moore, A AF Medarova, Zdravka Ghosh, Subrata K. Vangel, Mark Drake, Richard Moore, Anna TI Risk stratification of prostate cancer patients based on EPS-urine zinc content SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Article DE Diagnostics; prostate; cancer; zinc; risk-stratification ID RADICAL PROSTATECTOMY; ANTIGEN; MEN; UPGRADE; BIOPSY AB The early detection of prostate cancer is a life-saving event in patients harboring potentially aggressive disease. With the development of malignancy there is a dramatic reduction in the zinc content of prostate tissue associated with the inability of cancer cells to accumulate the ion. In the current study, we utilized endogenous zinc as a diagnostic biomarker for prostate cancer. We employed a novel fluorescent sensor for mobile zinc (ZPP1) to measure the concentration of zinc in thirty-nine patient samples of expressed prostatic secretion (EPS) in urine. We estimated the probability of classifying a subject as benign, low-risk, or high-risk as functions of the diagnostic test results using a non-informative prior Bayesian approach. Permutation tests and other non-parametric tests were also used. We demonstrated a significant trend in zinc score with disease and with disease risk (P = 0.03), and lack of a significant correlation between zinc score and PSA. We also showed that the proposed diagnostic is potentially superior to PSA for detecting high-risk disease. Considering that risk stratification represents an important unmet need, our method should advance the field of prostate cancer diagnostics and treatment planning. C1 [Medarova, Zdravka; Ghosh, Subrata K.; Vangel, Mark; Moore, Anna] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Sch Med,Dept Radiol,MIT HMS,Mol Imaging Lab, Charlestown, MA 02129 USA. [Drake, Richard] Eastern Virginia Med Sch, Ctr Biomed Prote, Dept Microbiol & Mol Cell Biol, Norfolk, VA 23507 USA. RP Moore, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Sch Med,Dept Radiol,MIT HMS,Mol Imaging Lab, Bldg 75,13th St, Charlestown, MA 02129 USA. EM zmedarova@partners.org; amoore@helix.mgh.harvard.edu FU National Cancer Institute [R00CA129070] FX Work at the Martinos Center for Biomedical Imaging was supported in part under grant R00CA129070 from the National Cancer Institute. ZPP1 was kindly provided by Prof. Stephen Lippard from MIT. NR 26 TC 6 Z9 6 U1 0 U2 3 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 2156-6976 J9 AM J CANCER RES JI Am. J. Cancer Res. PY 2014 VL 4 IS 4 BP 385 EP 393 PG 9 WC Oncology SC Oncology GA AO3WC UT WOS:000341266500007 PM 25057441 ER PT J AU Wahl, KR Margolis, A Lintner, K Hartkopf, K Martin, B AF Wahl, Kimberly R. Margolis, Amanda Lintner, Kimberly Hartkopf, Katherine Martin, Beth TI Impact and Application of Material Learned in a Pharmacy Residency Teaching Certificate Program SO AMERICAN JOURNAL OF PHARMACEUTICAL EDUCATION LA English DT Article DE teaching certificate program; pharmacy; residency training ID EXPERIENCES AB Objective. To describe the impact and application of material learned in a pharmacy resident teaching certificate program on the career experiences of alumni 1 to 11 years after completion of the program. Design. A teaching certificate program was established in 2001 that brought together residents from various training programs throughout Wisconsin to discuss essential educational skills in a dynamic learning environment. The purpose of the program was to teach participants the fundamental skills to continue to develop as a pharmacy educator throughout their career. Assessment. An electronic survey instrument was sent to alumni of the program. Greater than 70% of respondents agreed that the teaching certificate program reinforced their desire to teach in practice and that the program helped qualify them for their current or previous practice position. Alumni in academic positions more strongly agreed that the program changed their career interest to include academia and qualified them for their position in academia. Conclusions. A teaching certificate program can reinforce or stimulate interest among pharmacy residents in pursuing an academic career and prepare them for this role. Completion of the program led to a high level of confidence among the majority of alumni in their ability to precept students and residents and influenced some alumni involved in the hiring of pharmacists. C1 [Wahl, Kimberly R.; Margolis, Amanda; Martin, Beth] Univ Wisconsin, Sch Pharm, Madison, WI 53705 USA. [Wahl, Kimberly R.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Lintner, Kimberly] Meriter Hosp, Madison, WI USA. [Hartkopf, Katherine] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. RP Martin, B (reprint author), Univ Wisconsin, Sch Pharm, 1022 Rennebohm Hall,777 Highland Ave, Madison, WI 53705 USA. EM bamartin@pharmacy.wisc.edu NR 12 TC 4 Z9 4 U1 1 U2 3 PU AMER ASSOC COLL PHARMACY PI ALEXANDRIA PA 1426 PRINCE STREET, ALEXANDRIA, VA 22314-2815 USA SN 0002-9459 EI 1553-6467 J9 AM J PHARM EDUC JI Am. J. Pharm. Educ. PY 2014 VL 78 IS 6 AR 123 PG 8 WC Education, Scientific Disciplines; Pharmacology & Pharmacy SC Education & Educational Research; Pharmacology & Pharmacy GA AO5WT UT WOS:000341417800012 PM 25147395 ER PT J AU Hula, WD Fergadiotis, G Doyle, PJ AF Hula, William D. Fergadiotis, Gerasimos Doyle, Patrick J. TI A core outcome set for aphasia treatment research: Obstacles, risks, and benefits SO APHASIOLOGY LA English DT Editorial Material ID MEASUREMENT INVARIANCE; TRIALS; MATTER C1 [Hula, William D.; Doyle, Patrick J.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. [Hula, William D.; Doyle, Patrick J.] Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA USA. [Fergadiotis, Gerasimos] Portland State Univ, Dept Speech & Hearing Sci, Portland, OR 97207 USA. RP Hula, WD (reprint author), VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Univ Dr Div 132SP U, Pittsburgh, PA 15240 USA. EM william.hula@va.gov NR 14 TC 2 Z9 2 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0268-7038 EI 1464-5041 J9 APHASIOLOGY JI Aphasiology PY 2014 VL 28 IS 11 BP 1396 EP 1399 DI 10.1080/02687038.2014.930264 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA AO7CE UT WOS:000341508800008 ER PT J AU Makrigiorgos, GM AF Makrigiorgos, G. Mike TI COLD-PCR and digital COLD-PCR for ultra-sensitive detection of low-level resistance mutations in tumors and bin-fluids SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Meeting Abstract C1 [Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 EI 1791-244X J9 INT J MOL MED JI Int. J. Mol. Med. PY 2014 VL 34 SU 1 MA 259 BP S44 EP S44 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AO3ZM UT WOS:000341276000160 ER PT J AU Psychogios, N Constantinou, C Righi, V de Oliveira, CCF Shestov, AA Mintzopoulos, D Busquets, S Lopez-Soriano, FJ He, JX Milot, S Mindrinos, MN Lepine, F Rahme, LG Argiles, JM Tzika, AA AF Psychogios, Nikolaos Constantinou, Caterina Righi, Valerie Fontes de Oliveira, Cibely C. Shestov, Alexander A. Mintzopoulos, Dionyssios Busquets, Silvia Lopez-Soriano, Francisco J. He, Jianxin Milot, Sylvain Mindrinos, Michael N. Lepine, Francois Rahme, Laurence G. Argiles, Josep M. Tzika, Aria A. TI Mitochondrial uncoupling in mice skeletal muscle in cancer cachexia SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Meeting Abstract C1 [Psychogios, Nikolaos; Constantinou, Caterina; Righi, Valerie; Mintzopoulos, Dionyssios; Tzika, Aria A.] Harvard Univ, Sch Med, NMR Surg Lab, Massachusetts Gen Hosp, Boston, MA USA. [Constantinou, Caterina; He, Jianxin; Rahme, Laurence G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Constantinou, Caterina; He, Jianxin; Rahme, Laurence G.] Harvard Univ, Sch Med, Shriners Hosp Children, Boston, MA USA. [Psychogios, Nikolaos; Righi, Valerie; Tzika, Aria A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Cambridge, MA USA. [Fontes de Oliveira, Cibely C.; Busquets, Silvia; Argiles, Josep M.] Univ Barcelona, Dept Bioquim & Biol Mol, Canc Res Grp, Barcelona, Spain. [Shestov, Alexander A.] Univ Minnesota, Sch Med, Dept Radiol, Ctr Magnet Resonance Res, Minneapolis, MN 55455 USA. [Mindrinos, Michael N.] Stanford Univ, Dept Biochem, Sch Med, Stanford, CA 94305 USA. [Milot, Sylvain; Lepine, Francois] Univ Quebec, Inst Armand Frappier, INRS, Laval, PQ, Canada. EM psychogi@nmr.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 EI 1791-244X J9 INT J MOL MED JI Int. J. Mol. Med. PY 2014 VL 34 SU 1 MA 296 BP S53 EP S53 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AO3ZM UT WOS:000341276000197 ER PT J AU Spandidos, A Wang, XW Wang, HJ Seed, B AF Spandidos, Athanasia Wang, Xiaowei Wang, Huajun Seed, Brian TI The PrimerBank resource of human and mouse PCR primer pairs for gene expression, detection and quantification SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Meeting Abstract C1 [Spandidos, Athanasia; Wang, Xiaowei; Wang, Huajun; Seed, Brian] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Spandidos, Athanasia; Wang, Xiaowei; Wang, Huajun; Seed, Brian] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 EI 1791-244X J9 INT J MOL MED JI Int. J. Mol. Med. PY 2014 VL 34 SU 1 MA 242 BP S40 EP S40 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AO3ZM UT WOS:000341276000143 ER PT J AU Edwards, M Balldin, VH Hall, J O'Bryant, S AF Edwards, Melissa Balldin, Valerie Hobson Hall, James O'Bryant, Sid TI Combining Select Neuropsychological Assessment with Blood-Based Biomarkers to Detect Mild Alzheimer's Disease: A Molecular Neuropsychology Approach SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; biomarkers; molecular; neuropsychology ID CLOCK-DRAWING TEST; NATIONAL INSTITUTE; DEMENTIA; GUIDELINES; DIAGNOSIS; MARKERS AB Background: Current work has sought to establish a rapid and cost effective means of screening for Alzheimer's disease (AD) with the most recent findings showing utility of integrating blood-based biomarkers with cognitive measures. Objective: The current project sought to create a combined biomarker-cognitive profile to detect mild AD. Methods: Data was analyzed from 266 participants (129 AD cases [Early AD n = 93; Very Early AD n = 36]; 137 controls) enrolled in the Texas Alzheimer's Research and Care Consortium (TARCC). Non-fasting serum samples were collected from each participant and assayed via a multi-plex biomarker assay platform using electrochemiluminescence. Logistic Regression was utilized to detect early AD using two serum biomarkers (TNF alpha and IL7), demographic information (age), and one neuropsychological measure (Clock 4-point) as predictor variable. Disease severity was determined via Clinical Dementia Rating (CDR) scale global scores. Results: In the total sample (all levels of CDR scores), the combination of biomarkers, cognitive test score, and demographics yielded the obtained sensitivity (SN) of 0.94, specificity (SP) of 0.90, and an overall accuracy of 0.92. When examining early AD cases (i.e.m CDR = 0.5-1), the biomarker-cognitive profile yielded SN of 0.94, SP of 0.85, and an overall accuracy of 0.91. When restricted to very early AD cases (i.e., CDR = 0.5), the biomarker-cognitive profile yielded SN of 0.97 and SP of 0.72, with an overall accuracy of 0.91. Conclusions: The combination of demographics, two biomarkers, and one cognitive test created a biomarker-cognitive profile that was highly accurate in detecting the presence of AD, even in the very early stages. C1 [Edwards, Melissa] Univ N Texas, Dept Psychol, Denton, TX 76203 USA. [Balldin, Valerie Hobson] South Texas Vet Hlth Care Syst, Dept Psychol, San Antonio, TX USA. [Hall, James] Univ N Texas, Hlth Sci Ctr, Dept Psychiat, Ft Worth, TX 76107 USA. [Hall, James; O'Bryant, Sid] Univ N Texas, Hlth Sci Ctr, Inst Aging & Alzheimers Dis Res, Ft Worth, TX 76107 USA. [O'Bryant, Sid] Univ N Texas, Hlth Sci Ctr, Dept Internal Med, Ft Worth, TX 76107 USA. RP O'Bryant, S (reprint author), Univ N Texas, Hlth Sci Ctr, Dept Internal Med, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA. EM Sid.O'Bryant@unthsc.edu OI O'Bryant, Sid/0000-0003-0582-5266 FU National Institute on Aging (NIA) [R01AG039389, P30AG12300]; Texas Council on Alzheimer's Disease and Related Disorders FX Research reported in this publication was supported by the National Institute on Aging (NIA) under Award Numbers R01AG039389 and P30AG12300. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This research was also made possible by a grant from the Texas Council on Alzheimer's Disease and Related Disorders to the Texas Alzheimer's Research & Care Consortium (TARCC)*. NR 28 TC 1 Z9 1 U1 0 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2014 VL 42 IS 2 BP 635 EP 640 DI 10.3233/JAD-140852 PG 6 WC Neurosciences SC Neurosciences & Neurology GA AO7ZP UT WOS:000341572000025 PM 24916542 ER PT J AU Tao, YL Wang, Y Rogers, JT Wang, FD AF Tao, Yunlong Wang, Yu Rogers, Jack T. Wang, Fudi TI Perturbed Iron Distribution in Alzheimer's Disease Serum, Cerebrospinal Fluid, and Selected Brain Regions: A Systematic Review and Meta-Analysis SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Review DE Alzheimer's disease; cerebrospinal fluid; iron; iron overload; meta-analysis; serum iron; systematic review ID MILD COGNITIVE IMPAIRMENT; AMYLOID PRECURSOR PROTEIN; NEUTRON-ACTIVATION ANALYSIS; IN-VIVO EVALUATION; REDOX-ACTIVE IRON; OXIDATIVE STRESS; NEURODEGENERATIVE DISEASES; TRACE-ELEMENTS; PARKINSONS-DISEASE; MULTIPLE-SCLEROSIS AB Background: The homeostasis and physiological role of iron in Alzheimer's disease (AD) has been debated for decades. Overall, it has been difficult to reach a consensus to prove marked disease-associated changes in the iron content of the AD brain, blood, or cerebrospinal fluid (CSF). Objectives: We sought to contribute to resolve this issue by quantifying the iron content in serum, CSF, and sub-regions of the AD brain. Methods: We conducted a comprehensive systematic meta-analysis and review of multiple observational studies till October 2013 that investigated the iron content in AD serum, CSF, or brain tissue. Results: 2,556 publications were screened. Forty-three eligible studies with 1,813 AD patients and 2,401 healthy controls were identified. Twenty-one studies investigated the serum iron in AD while seven and nineteen studies investigated the CSF iron and various brain regions iron respectively. Our meta-analysis showed that serum iron was significant lower in AD than healthy controls. CSF iron appeared not to be affected by AD although more studies are required due to the relative small number of CSF studies reported to date. We critically analyzed iron content in twelve selective brain regions by separated meta-analyses using cross-referenced statistical methods. We found that eight specific brain regions had higher iron concentrations that correlated with the clinical diagnosis of AD in a statistically validated manner. Conclusions: These data provided rigorous statistical support for the model that iron homeostasis was changed in AD patients, including the finding of lower iron in their serum and evidence for iron overload in several specific brain regions. C1 [Tao, Yunlong; Wang, Fudi] Zhejiang Univ, Collaborat Innovat Ctr Diag & Treatment Infect Di, Sch Publ Hlth,Inst Nutr & Food Safety, Lab Nutr & Metab,Res Ctr Nutr & Hlth,Dept Nutr, Hangzhou 310058, Zhejiang, Peoples R China. [Tao, Yunlong] Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai, Peoples R China. [Wang, Yu] Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, Key Lab Computat Biol, Shanghai, Peoples R China. [Rogers, Jack T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Neurochem Lab, Charlestown, MA USA. RP Wang, FD (reprint author), Zhejiang Univ, Sch Publ Hlth, Dept Nutr, 866 Yuhangtang Rd, Hangzhou 310058, Zhejiang, Peoples R China. EM fwang@zju.edu.cn FU Chinese Ministry of Science and Technology [2011CB966200, 2012BAD33B05]; Chinese National Natural Science Foundation [31225013, 31330036, 31030039]; Zhejiang University; NIH [R21 NS077079-01A]; Alzheimer's Association FX This work was supported by research grants from the Chinese Ministry of Science and Technology (grant numbers 2011CB966200 and 2012BAD33B05 to F. W.) and Chinese National Natural Science Foundation (grant numbers 31225013, 31330036 and 31030039 to F. W.). This work was also supported by the Distinguished Professorship Program from Zhejiang University (to F. W.). NIH support from R21 NS077079-01A to and a Zenith Award from the Alzheimer's Association to Jack Rogers. NR 90 TC 10 Z9 10 U1 2 U2 15 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2014 VL 42 IS 2 BP 679 EP 690 DI 10.3233/JAD-140396 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AO7ZP UT WOS:000341572000029 PM 24916541 ER PT J AU Talbot, LS Neylan, TC Metzler, TJ Cohen, BE AF Talbot, Lisa S. Neylan, Thomas C. Metzler, Thomas J. Cohen, Beth E. TI The Mediating Effect of Sleep Quality on the Relationship between PTSD and Physical Activity SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE posttraumatic stress disorder; sleep quality; physical activity ID POSTTRAUMATIC-STRESS-DISORDER; CORONARY-HEART-DISEASE; NATIONALLY REPRESENTATIVE SAMPLE; METABOLIC SYNDROME; HEALTH BEHAVIORS; GENERAL-POPULATION; VIETNAM VETERANS; WEIGHT-GAIN; RISK; ASSOCIATION AB Study Objectives: Physical inactivity is linked to health outcomes such as obesity, diabetes, and psychiatric disorders. Sleep disturbance has been linked to the same adverse outcomes. We examine the influence of sleep on physical activity as a novel approach to understand these relationships. Specifically, our objective was to determine whether low sleep quality predicts low physical activity in posttraumatic stress disorder (PTSD), a disorder associated with sleep disturbance, physical inactivity, and poor health outcomes. Methods: We used data from the Mind Your Heart Study, a prospective cohort study of 736 outpatients recruited from two Department of Veterans Affairs (VA) medical centers. We assessed PTSD with the Clinician Administered PTSD Scale, sleep quality using an item from the Pittsburgh Sleep Quality Index, and physical activity by self-report at baseline and again one year later. Hierarchical multiple regression models and structural equation modeling were used to examine the relationships among PTSD, sleep, and physical activity. Results: Sleep quality but not PTSD status was prospectively associated with lower physical activity in a model adjusting for age, sex, apnea probability, depression, body mass index, and baseline physical activity (beta = 0.129, SE = 0.072, p < 0.01). Structural equation modeling indicated that the results were consistent with sleep quality statistically mediating the relationship between PTSD status at baseline and physical activity one year later. Conclusions: Worse sleep quality predicts lower physical activity in PTSD, providing possible evidence for a behavioral pathway from disturbed sleep to poor physical health outcomes. C1 [Talbot, Lisa S.; Neylan, Thomas C.; Metzler, Thomas J.; Cohen, Beth E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Talbot, Lisa S.; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Cohen, Beth E.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Talbot, LS (reprint author), San Francisco VA Med Ctr 116H, 4150 Clement St, San Francisco, CA 94121 USA. EM lisa.talbot@gmail.com FU National Heart, Lung, and Blood Institute [K23 HL 094765]; Irene Perstein Foundation; Mental Illness Research and Education Clinical Center of the US Veterans Health Administration FX This was not an industry supported study. This research was supported by grants from the National Heart, Lung, and Blood Institute (BEC: K23 HL 094765), the Irene Perstein Foundation, and the Mental Illness Research and Education Clinical Center of the US Veterans Health Administration. The authors have indicated no financial conflicts of interest. NR 50 TC 8 Z9 8 U1 1 U2 8 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 EI 1550-9397 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2014 VL 10 IS 7 BP 795 EP 801 DI 10.5664/jcsm.3878 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AO2GN UT WOS:000341136100014 PM 25024659 ER PT J AU Jung, S Zaremba, S Heisig, A Eikermann, M AF Jung, Stefanie Zaremba, Sebastian Heisig, Anne Eikermann, Matthias TI Elevated Body Position Early after Delivery Increased Airway Size during Wakefulness, and Decreased Apnea Hypopnea Index in a Woman with Pregnancy Related Sleep Apnea SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE pregnancy; polysomnography; sleep apnea; positional therapy; post-partum AB We report a patient with pregnancy related obstructive sleep apnea ([OSA]; apnea hypopnea index [AHI] 18/h) early after delivery, with improvement of AHI by 87% following 45-degree elevation in body position compared with the non-elevated position. Improvement associated with this position may be explained, at least in part, by an increased upper airway diameter (as measured during wakefulness). Sleep apnea in this patient resolved at 9 months postpartum. This observation suggests that 45-degree elevated body position may be an effective treatment of pregnancy related OSA during the postpartum period. C1 [Jung, Stefanie; Zaremba, Sebastian; Heisig, Anne; Eikermann, Matthias] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Jung, Stefanie] Univ Marburg, Teaching Hosp, DRK Kinderklin Siegen, Dept Pediat Surg & Pediat Urol, Marburg, Germany. [Zaremba, Sebastian] Univ Bonn, Univ Hosp Bonn, Dept Neurol, Bonn, Germany. [Eikermann, Matthias] Univ Duisburg Essen, Univ Hosp Essen, Dept Anesthesia & Crit Care, Essen, Germany. RP Zaremba, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM sebastian.zaremba@ukb.uni-bonn.de FU ResMed Foundation; Merck; Massimo FX This was not an industry supported study. Dr. Eikermann has received research funding from ResMed Foundation, Merck and Massimo. The other authors have indicated no financial conflicts of interest. NR 12 TC 2 Z9 2 U1 1 U2 3 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 EI 1550-9397 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2014 VL 10 IS 7 BP 815 EP 817 DI 10.5664/jcsm.3886 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA AO2GN UT WOS:000341136100018 PM 25024663 ER PT J AU Wilkerson, MD Cabanski, CR Sun, W Hoadley, KA Walter, V Mose, LE Troester, MA Hammerman, PS Parker, JS Perou, CM Hayes, DN AF Wilkerson, Matthew D. Cabanski, Christopher R. Sun, Wei Hoadley, Katherine A. Walter, Vonn Mose, Lisle E. Troester, Melissa A. Hammerman, Peter S. Parker, Joel S. Perou, Charles M. Hayes, D. Neil TI Integrated RNA and DNA sequencing improves mutation detection in low purity tumors SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; SOMATIC POINT MUTATIONS; HUMAN BREAST-TUMORS; HUMAN TRANSCRIPTOME; WIDESPREAD RNA; MOLECULAR DIAGNOSIS; VARIANT DETECTION; WHOLE GENOME; HUMAN CANCER; EXOME AB Identifying somatic mutations is critical for cancer genome characterization and for prioritizing patient treatment. DNA whole exome sequencing (DNA-WES) is currently the most popular technology; however, this yields low sensitivity in low purity tumors. RNA sequencing (RNA-seq) covers the expressed exome with depth proportional to expression. We hypothesized that integrating DNA-WES and RNA-seq would enable superior mutation detection versus DNA-WES alone. We developed a first-of-its-kind method, called UNCeqR, that detects somatic mutations by integrating patient-matched RNA-seq and DNA-WES. In simulation, the integrated DNA and RNA model outperformed the DNA-WES only model. Validation by patient-matched whole genome sequencing demonstrated superior performance of the integrated model over DNA-WES only models, including a published method and published mutation profiles. Genome-wide mutational analysis of breast and lung cancer cohorts (n = 871) revealed remarkable tumor genomics properties. Low purity tumors experienced the largest gains in mutation detection by integrating RNA-seq and DNA-WES. RNA provided greater mutation signal than DNA in expressed mutations. Compared to earlier studies on this cohort, UNCeqR increased mutation rates of driver and therapeutically targeted genes (e.g. PIK3CA, ERBB2 and FGFR2). In summary, integrating RNA-seq with DNA-WES increases mutation detection performance, especially for low purity tumors. C1 [Wilkerson, Matthew D.; Cabanski, Christopher R.; Hoadley, Katherine A.; Walter, Vonn; Mose, Lisle E.; Troester, Melissa A.; Parker, Joel S.; Perou, Charles M.; Hayes, D. Neil] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Wilkerson, Matthew D.; Sun, Wei; Hoadley, Katherine A.; Parker, Joel S.; Perou, Charles M.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Cabanski, Christopher R.] Washington Univ, Genome Inst, St Louis, MO 63108 USA. [Sun, Wei] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. [Troester, Melissa A.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Hammerman, Peter S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Hammerman, Peter S.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Hayes, D. Neil] Univ N Carolina, Div Med Oncol, Dept Internal Med, Multidisciplinary Thorac Oncol Program, Chapel Hill, NC 27599 USA. RP Wilkerson, MD (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. EM mwilkers@med.unc.edu; hayes@med.unc.edu OI Perou, Charles/0000-0001-9827-2247 FU National Cancer Institute [F32CA142039, P50-CA058223]; National Institutes of Health [U24 CA143848, U24 CA143848-02S1] FX National Cancer Institute [F32CA142039 to M.D.W., Breast SPORE P50-CA058223 to C.M.P.]; National Institutes of Health [U24 CA143848 to C.M.P., D.N.H and U24 CA143848-02S1 to C.M.P., D.N.H.]. Funding for open access charge: National Institutes of Health. NR 52 TC 18 Z9 18 U1 2 U2 7 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 13 AR e107 DI 10.1093/nar/gku489 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AO7ER UT WOS:000341515400005 PM 24970867 ER PT S AU Mallipattu, SK He, JC AF Mallipattu, Sandeep K. He, John C. BE Liu, ZH He, JC TI Podocyte Injury in HIV-Associated Nephropathy SO PODOCYTOPATHY SE Contributions to Nephrology LA English DT Article; Book Chapter ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; HIV-1-ASSOCIATED NEPHROPATHY; TRANSGENIC MICE; EXPRESSION; KIDNEY; APOL1; INFECTION; GENES; SUSCEPTIBILITY; EPITHELIUM AB Prior to the widespread use of antiretroviral therapy, HIV-associated nephropathy (HIVAN) was the leading cause of end-stage renal disease among individuals of African descent. HIVAN, a rapidly progressing glomerulopathy, is characterized by collapsing focal segmental glomerulosclerosis, podocyte hypertrophy, and proliferation of epithelial cells overlying the Bowman's space. Although the origin of these proliferating cells is debatable, a large body of evidence suggests that podocyte dysfunction occurs in HIVAN. In the last decade, several groups have demonstrated that the podocyte serves as a reservoir for the virus and podocyte dysfunction is a direct result of specific viral protein expression. The viral protein, nef, directly activates several signaling pathways, resulting in podocyte dedifferentiation and proliferation. Today, with the widespread use of antiretroviral therapy, classical HIVAN is rare. Nonetheless, as patients with chronically infected HIV live longer, many still succumb to chronic kidney disease due to coexisting illnesses such as diabetes and hypertension. However, it remains unclear whether this viral reservoir serves a medium for development of non-HIVAN-related kidney diseases such as diabetic nephropathy. We also provide some insights into potential areas of research in characterizing podocyte biology in this changing spectrum of HIV-related kidney disease. (C) 2014 S. Karger AG, Basel C1 [Mallipattu, Sandeep K.] SUNY Stony Brook, Div Nephrol, Dept Med, Sch Med, Stony Brook, NY 11794 USA. [He, John C.] Icahn Sch Med Mt Sinai, Div Nephrol, Dept Med, New York, NY 10029 USA. [He, John C.] James J Peters VA Med Ctr, Renal Sect, New York, NY USA. RP He, JC (reprint author), Icahn Sch Med Mt Sinai, Dept Med Nephrol, One Gustave L Levy Pl,Box 1243, New York, NY 10029 USA. EM cijiang.he@mssm.edu RI Mallipattu , Sandeep/M-7009-2014 NR 30 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0302-5144 BN 978-3-318-02651-1; 978-3-318-02650-4 J9 CONTRIB NEPHROL JI Contrib.Nephrol. PY 2014 VL 183 BP 181 EP 190 DI 10.1159/000360113 PG 10 WC Cell Biology; Urology & Nephrology SC Cell Biology; Urology & Nephrology GA BB1TT UT WOS:000341359900015 ER PT S AU Sharma, S Mallipattu, SK Zhong, YF He, JC AF Sharma, Shuchita Mallipattu, Sandeep K. Zhong, Yifei He, John C. BE Liu, ZH He, JC TI Retinoic Acid: A Potential Pharmacologic Approach in the Treatment of Podocytopathy SO PODOCYTOPATHY SE Contributions to Nephrology LA English DT Article; Book Chapter ID HIV-ASSOCIATED NEPHROPATHY; GLOMERULAR-DISEASE; EXPRESSION; GLOMERULONEPHRITIS; DIFFERENTIATION; RECEPTORS; PODOCYTES; CELLS; MODEL; RATS AB In the setting of injury, podocytes can undergo dedifferentiation and proliferation, apoptosis, or cell detachment, resulting in proteinuria. Significant injury resulting in a loss of podocytes contributes to progressive kidney disease. Consequently, therapies that prevent podocyte injury and promote their regeneration will have a major clinical impact on glomerular disease. All-trans-retinoic acid (RA), which is a derivative of vitamin A, has many cellular functions including induction of cell differentiation, regulation of apoptosis, and inhibition of inflammation and proliferation. In addition to its established role in the treatment of variety of cancers, RA has been demonstrated to provide protection in various experimental models of kidney diseases with podocyte injury. RA produces its beneficial effects in the kidney due to its anti-inflammatory and antiproliferative effects. Also, RA helps maintain the normal morphology and preserves the differentiation markers of the podocytes. RA produces its effects in the podocytes via retinoic acid receptor-a (RAR-alpha). Treatment with RAR-a agonist, Am580, has a similar efficacy as RA in a mouse model of HIVAN. However, due to its systemic toxicity, clinical studies evaluating the use of RA have been challenging. Therefore, novel RAR-alpha agonist such as BD4 has been synthesized, which has a similar efficacy as RA and Am580, with lower toxicity. (C) 2014 S. Karger AG, Basel C1 [Sharma, Shuchita; He, John C.] Icahn Sch Med Mt Sinai, Div Nephrol, Dept Med, New York, NY 10029 USA. [Mallipattu, Sandeep K.] SUNY Stony Brook, Div Nephrol, Dept Med, Sch Med, Stony Brook, NY USA. [He, John C.] James J Peters VA Med Ctr, Div Renal, New York, NY USA. [Zhong, Yifei] Shanghai Univ Tradit Chinese Med, Longhua Hosp, Dept Nephrol, Shanghai, Peoples R China. RP He, JC (reprint author), Icahn Sch Med Mt Sinai, Dept Med Nephrol, One Gustave L Levy Pl,Box 1243, New York, NY 10029 USA. EM cijiang.he@mssm.edu RI Mallipattu , Sandeep/M-7009-2014 NR 26 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0302-5144 BN 978-3-318-02651-1; 978-3-318-02650-4 J9 CONTRIB NEPHROL JI Contrib.Nephrol. PY 2014 VL 183 BP 191 EP 198 DI 10.1159/000360114 PG 8 WC Cell Biology; Urology & Nephrology SC Cell Biology; Urology & Nephrology GA BB1TT UT WOS:000341359900016 ER PT S AU Lee, S Braun, CR Bird, GH Walensky, LD AF Lee, Susan Braun, Craig R. Bird, Gregory H. Walensky, Loren D. BE Ashkenazi, A Yuan, J Wells, JA TI Photoreactive Stapled Peptides to Identify and Characterize BCL-2 Family Interaction Sites by Mass Spectrometry SO REGULATED CELL DEATH PT A: APOPTOTIC MECHANISMS SE Methods in Enzymology LA English DT Review; Book Chapter ID AMINO-ACID-SEQUENCES; BH3 HELIX; STRUCTURAL BIOLOGY; PROTEIN STRUCTURES; DOCKING APPROACH; APOPTOSIS; ACTIVATION; DOMAINS; BAX; COMPLEX AB Protein interactions dictate a myriad of cellular activities that maintain health or cause disease. Dissecting these binding partnerships, and especially their sites of interaction, fuels the discovery of signaling pathways, disease mechanisms, and next-generation therapeutics. We previously applied all-hydrocarbon peptide stapling to chemically restore a-helical shape to bioactive motifs that become unfolded when taken out of context from native signaling proteins. For example, we developed stabilized alphahelices of BCL-2 domains (SAHBs) to dissect and target protein interactions of the BCL-2 family, a critical network that regulates the apoptotic pathway. SAHBs are alpha-helical surrogates that bind both stable and transient physiologic interactors and have effectively uncovered novel sites of BCL-2 family protein interaction. To leverage stapled peptides for proteomic discovery, we describe our conversion of SAHBs into photoreactive agents that irreversibly capture their protein targets and facilitate rapid identification of the peptide helix binding sites. We envision that the development of photoreactive stapled peptides will accelerate the discovery of novel and unanticipated protein interactions and how they impact health and disease. C1 [Lee, Susan; Braun, Craig R.; Bird, Gregory H.; Walensky, Loren D.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Lee, Susan; Braun, Craig R.; Bird, Gregory H.; Walensky, Loren D.] Dana Farber Canc Inst, Linde Program Canc Chem Biol, Boston, MA 02115 USA. [Lee, Susan; Braun, Craig R.; Bird, Gregory H.; Walensky, Loren D.] Harvard Univ, Sch Med, Dept Pediat, Childrens Hosp Boston, Boston, MA 02115 USA. [Braun, Craig R.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Walensky, LD (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM loren_walensky@dfci.harvard.edu NR 41 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-417175-6; 978-0-12-417158-9 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2014 VL 544 BP 25 EP 48 DI 10.1016/B978-0-12-417158-9.00002-9 PG 24 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BB1VQ UT WOS:000341414700003 ER PT S AU Nicholls, SB Hyman, BT AF Nicholls, Samantha B. Hyman, Bradley T. BE Ashkenazi, A Yuan, J Wells, JA TI Measuring Caspase Activity In Vivo SO REGULATED CELL DEATH PT A: APOPTOTIC MECHANISMS SE Methods in Enzymology LA English DT Review; Book Chapter ID RED FLUORESCENT PEPTIDE; REAL-TIME DETECTION; IMAGING APOPTOSIS; LIVING CELLS; MEMBRANE-PERMEANT; LIVE CELLS; FRET; ACTIVATION; INHIBITORS; PROTEINS AB Caspases are a family of integral proteases playing a role in apoptosis. The importance of apoptosis in disease has made these proteases not only an attractive drug target but also a focal point for measuring apoptosis in vivo. The critical role caspases play in determining cell death has led to the development of a wide array of technologies to measure caspase activity in vivo, ranging from small molecule PET imaging reagents to fluorescent and luminescent protein-based reporters used in whole animal and cell-based applications. This chapter reviews this wide range of technologies available as well as the most appropriate applications for each reagent and the mechanism of how it measures caspase activity in vivo. C1 [Nicholls, Samantha B.; Hyman, Bradley T.] Harvard Univ, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol,Alzheimers Dis Res Lab,Med Sch, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol,Alzheimers Dis Res Lab,Med Sch, Charlestown, MA 02129 USA. EM bhyman@partners.org NR 46 TC 0 Z9 0 U1 2 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-417175-6; 978-0-12-417158-9 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2014 VL 544 BP 251 EP 269 DI 10.1016/B978-0-12-417158-9.00010-8 PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BB1VQ UT WOS:000341414700011 ER PT B AU Koenig, CJ Robinson, JD AF Koenig, Christopher J. Robinson, Jeffrey D. BE Whaley, BB TI CONVERSATION ANALYSIS Understanding the Structure of Health Talk SO RESEARCH METHODS IN HEALTH COMMUNICATION: PRINCIPLES AND APPLICATION LA English DT Article; Book Chapter ID PHYSICIANS OPENING QUESTIONS; TREATMENT RECOMMENDATIONS; MEDICAL INTERACTIONS; PATIENT INTERACTION; PARENT RESISTANCE; PRIMARY-CARE; COMMUNICATION; ANTIBIOTICS; VISITS; FORMULATIONS C1 [Koenig, Christopher J.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Koenig, Christopher J.] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA. [Robinson, Jeffrey D.] Univ Dayton, Dayton, OH 45469 USA. RP Koenig, CJ (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. OI Koenig, Christopher J./0000-0003-0884-4120 NR 74 TC 1 Z9 1 U1 0 U2 1 PU ROUTLEDGE PI ABINGDON PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND BN 978-0-415-53186-3; 978-0-203-11529-9; 978-0-415-53185-6 PY 2014 BP 119 EP 140 PG 22 WC Communication; Health Policy & Services SC Communication; Health Care Sciences & Services GA BB1TI UT WOS:000341356000008 ER PT B AU Kanauchi, O Larauche, M Tache, Y AF Kanauchi, Osamu Larauche, Muriel Tache, Yvette BE Watson, RR Preedy, VR Zibadi, S TI Development of Functional Foods (Enzyme-Treated Rice Fiber) from Rice By-products SO WHEAT AND RICE IN DISEASE PREVENTION AND HEALTH: BENEFITS, RISKS AND MECHANISMS OF WHOLE GRAINS IN HEALTH PROMOTION LA English DT Article; Book Chapter ID IRRITABLE-BOWEL-SYNDROME; GERMINATED BARLEY FOODSTUFF; DEXTRAN SULFATE SODIUM; MUCOSAL IMMUNE-SYSTEM; FECAL MICROFLORA; AMELIORATES INFLAMMATION; WHEAT BRAN; DISEASE; COLITIS; MODULATION C1 [Kanauchi, Osamu] Kirin Holdings Co Ltd, Strateg Res & Dev Dept, Chuo Ku, Tokyo, Japan. [Kanauchi, Osamu] Shiga Univ Med Sci, Otzu, Japan. [Larauche, Muriel; Tache, Yvette] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Larauche, Muriel; Tache, Yvette] Univ Calif Los Angeles, Div Digest Dis, Oppenheimer Family Ctr Neurobiol Stress, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Kanauchi, O (reprint author), Kirin Holdings Co Ltd, Strateg Res & Dev Dept, Chuo Ku, Tokyo, Japan. OI Larauche, Muriel/0000-0003-3320-3675 NR 79 TC 0 Z9 0 U1 0 U2 3 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-404604-7; 978-0-12-401716-0 PY 2014 BP 521 EP 532 DI 10.1016/B978-0-12-401716-0.00040-4 PG 12 WC Public, Environmental & Occupational Health; Nutrition & Dietetics SC Public, Environmental & Occupational Health; Nutrition & Dietetics GA BB1MZ UT WOS:000341214700041 ER PT J AU De Freitas, J Falls, BA Hague, OS Bursztajn, HJ AF De Freitas, Julian Falls, Brian A. Hague, Omar S. Bursztajn, Harold J. TI Recognizing Misleading Pharmaceutical Marketing Online SO JOURNAL OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW LA English DT Article ID HEALTH INFORMATION; DRUG COMPANIES; INTERNET AB In light of decision-making psychology, this article details how drug marketing operates across established and novel web domains and identifies some common misleading trends and influences on prescribing and patient-initiated medication requests. The Internet has allowed pharmaceutical marketing to become more salient than ever before. Although the Internet's growth has improved the dissemination of pharmaceutical information, it has also led to the increased influence of misleading pharmaceutical marketing. Such mismarketing is of concern, especially in psychiatry, since psychotropics generate considerable revenue for drug companies. In a climate of resource-limited drug regulation and time-strapped physicians, we recommend improving both independent monitoring and consumer awareness of Internet-enabled, potentially misleading, pharmaceutical marketing influences. C1 [De Freitas, Julian] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. [Falls, Brian A.] Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Hague, Omar S.; Bursztajn, Harold J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Psychiat, Cambridge, MA 02138 USA. [Hague, Omar S.; Bursztajn, Harold J.] Massachusetts Mental Hlth Ctr, Cambridge, MA USA. [Hague, Omar S.] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. RP Bursztajn, HJ (reprint author), 96 Larchwood Dr, Cambridge, MA 02138 USA. EM harold_bursztajn@hms.harvard.edu NR 33 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD PSYCHIATRY & LAW PI BLOOMFIELD PA ONE REGENCY DR, PO BOX 30, BLOOMFIELD, CT 06002 USA SN 1093-6793 EI 1943-3662 J9 J AM ACAD PSYCHIATRY JI J. Am. Acad. Psychiatry Law PY 2014 VL 42 IS 2 BP 219 EP 225 PG 7 WC Law; Psychiatry SC Government & Law; Psychiatry GA AL6GA UT WOS:000339229400012 ER PT J AU Patel, S Davila, J Patel, S Norman, D AF Patel, Sachin Davila, Javier Patel, Sonam Norman, Dennis TI HEALTH PERCEPTIONS AMONG URBAN AMERICAN INDIANS WITH TYPE II DIABETES SO AMERICAN INDIAN AND ALASKA NATIVE MENTAL HEALTH RESEARCH LA English DT Article ID NATIVE-AMERICANS; ADHERENCE; PREVENTION; DEPRESSION; MANAGEMENT; MEDICINE; BARRIERS; ILLNESS; OBESITY; ADULTS AB Since the 1940s, American Indians (AIs) have increasingly urbanized, moving off of reservations in large part due to federal policies of tribal termination and relocation. Though previous AI research has largely focused on reservation-associated challenges, many of these same challenges persist among urban AI populations. One mutual concern is the growing prevalence and incidence of type II diabetes mellitus (T2DM). While behavioral, genetic, and socioeconomic determinants of T2DM have been explored, much less is known about the influence of cultural and psychosocial factors. Recent studies suggest that the way AIs perceive diabetes may affect their health trajectory and explain their poor prognosis. Through the use of the Illness Perception Questionnaire, we explored this hypothesis in a pilot study of urban AI with T2DM living in Los Angeles County. We found that the majority of participants have a neutral perception about their diabetes: They view their condition to be long lasting yet treatable and indicate reasonable understanding of its symptoms and progression. We also identified "personal control, "the level of perceived control one has over his or her disease, as a strong correlate of overall illness perception and, thus, a potentially useful psychological metric. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Native Amer Program, Cambridge, MA 02138 USA. [Davila, Javier; Patel, Sonam] Amer Indian Healing Ctr, Whittier, CA USA. RP Norman, D (reprint author), 14 Story St, Cambridge, MA 02138 USA. EM sachin_patel@hms.harvard.edu; dnorman@partners.org NR 30 TC 0 Z9 0 U1 3 U2 5 PU UNIV PRESS COLORADO PI NIWOT PA PO BOX 849, NIWOT, CO 80544 USA SN 0893-5394 EI 1533-7731 J9 AM INDIAN ALASKA NAT JI Am. Indian Alsk. Nativ. Ment. Health Res. PY 2014 VL 21 IS 2 BP 28 EP 42 PG 15 WC Psychology, Clinical SC Psychology GA AN6GQ UT WOS:000340693400002 PM 25111842 ER PT J AU Jackevicius, CA Wong, J Aroustamian, I Gee, M Mody, FV AF Jackevicius, Cynthia A. Wong, Joyce Aroustamian, Irina Gee, Manyee Mody, Freny Vaghaiwalla TI Rates and predictors of ACE inhibitor discontinuation subsequent to elevated serum creatinine: a retrospective cohort study SO BMJ OPEN LA English DT Article ID CONVERTING ENZYME-INHIBITOR; HIGH BLOOD-PRESSURE; RENAL-INSUFFICIENCY; HEART-FAILURE; THERAPY; KIDNEY; DISEASE; CARE AB Objectives: ACE inhibitors (ACEI) are underutilised despite cardiovascular benefits, in part due to concerns of known transient elevations in serum creatinine (SCr) after initiation. Our objectives were to evaluate rates and predictors of ACEI discontinuation after SCr elevation post-ACEI initiation since limited data are available that examine this issue. Setting: Primary and tertiary Veterans healthcare system in Los Angeles, California, USA Participants: 3039 outpatients initiating an ACEI with a SCr measured within 6 months prior to and approximately 3 months after initiating an ACEI. Patients were divided into three groups (SCr <1.5, 1.5-2 and >2). Primary and secondary outcome measures: Rates and factors associated with ACEI discontinuation subsequent to SCr elevation after ACEI initiation and for patients with baseline SCr >2 mg/dL, the change in SCr associated with chronic use. Predictors were identified using multivariate logistic regression modelling. Results: At 3 months follow-up, for those with an increase in SCr, the mean increase post-ACEI initiation was 26%, ranging from -0.01 mg/dL to 0.42 mg/dL varying according to a level of baseline renal function. ACEI discontinuation was higher in patients with elevated baseline SCr (19/165, 11.5%) compared with those with SCr <1.5 (135/2497, 5.4%), and those with SCr 1.5-2.0 (28/377, 7.4%). Male patients, and those with heart failure were less likely to discontinue ACEI after an elevation of SCr post-ACEI initiation, while those taking non-steroidal anti-inflammatory drugs, diuretics and beta-blockers were more likely to discontinue ACEI. Conclusions: SCr increases <30% on average within 3 months of ACEI initiation, with subsequent discontinuation rates varying by baseline SCr. Elevation in SCr was not associated with ACEI discontinuation rates. In patients with SCr >2 mg/dL at baseline, despite an acute increase in SCr after ACEI initiation, chronic ACEI use was associated with a decrease in SCr in most patients. C1 [Jackevicius, Cynthia A.; Wong, Joyce; Aroustamian, Irina] Western Univ Hlth Sci, Dept Pharm Practice & Adm, Pomona, CA USA. [Jackevicius, Cynthia A.; Gee, Manyee; Mody, Freny Vaghaiwalla] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med & Pharm, Los Angeles, CA 90073 USA. [Jackevicius, Cynthia A.] Univ Toronto, Fac Med, Inst Hlth Policy Management & Evaluat, Toronto, ON M5S 1A1, Canada. [Jackevicius, Cynthia A.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Univ Hlth Network, Dept Pharm, Toronto, ON, Canada. [Mody, Freny Vaghaiwalla] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA. RP Mody, FV (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med & Pharm, Los Angeles, CA 90073 USA. EM freny.mody@va.gov NR 21 TC 2 Z9 2 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2014 VL 4 IS 8 AR e005181 DI 10.1136/bmjopen-2014-005181 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA AN7KT UT WOS:000340779400021 PM 25232564 ER PT J AU Gong, B Levine, S Barnum, SR Pasinetti, GM AF Gong, Bing Levine, Samara Barnum, Scott R. Pasinetti, Giulio M. TI Role of Complement Systems in IVIG Mediated Attenuation of Cognitive Deterioration in Alzheimer's Disease SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Alzheimer's disease; cognitive function; complement component; immunotherapy; IVIG; synaptic plasticity ID CENTRAL-NERVOUS-SYSTEM; HUMAN INTRAVENOUS IMMUNOGLOBULIN; ANAPHYLATOXIN C5A NEUROPROTECTS; LONG-TERM POTENTIATION; MOUSE MODEL; SYNAPTIC PLASTICITY; GENE-EXPRESSION; AMYLOID-BETA; NEURODEGENERATIVE DISORDERS; HIPPOCAMPAL-NEURONS AB Human intravenous immunoglobulin (IVIG) has been indicated as a potential therapy for autoimmune neurological disorders, as well as in many neurodegenerative diseases, with various underlying therapeutic mechanisms such as regulation of T-cell trafficking, cytokines, Fc receptor blocking, and interruption of complement activation cascade. In Alzheimer's disease (AD), IVIG presents naturally occurring antibodies against amyloid-beta (A beta) aggregation, thus IVIG immunotherapy may increase the clearance of A beta and protect brain function. Recently, we and others reported that besides A beta clearance, IVIG specifically regulates the levels of complement-derived anaphylatoxins, such as C5a and C3, which play an important role in the regulation of AMPA and NMDA receptor expression in the brain and further upregulate the AMPA-PKA-CREB signaling pathway and synaptic function in AD mouse models. Since down-regulation of complement components has been linked with deficits of cognitive function in age-related dementia following the decline of innate immunity during aging, the IVIG immunotherapy could be an attractive novel AD therapeutic through its local regulation of C3, C5a component levels in brain. C1 [Gong, Bing; Levine, Samara; Pasinetti, Giulio M.] Icahn Sch Med Mt Sinai, Ctr Excellence Novel Approaches Neurotherapeut, Dept Neurol, New York, NY 10029 USA. [Barnum, Scott R.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. [Pasinetti, Giulio M.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY 10468 USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Neurol, 1468 Madison Ave, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu FU Veterans Administration FX The studies described here were supported in part from a grant from the Veterans Administration and by discretionary funding to G.M.P. NR 82 TC 3 Z9 3 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 EI 1875-5828 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PY 2014 VL 11 IS 7 BP 637 EP 644 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AN9LG UT WOS:000340927500003 PM 25115545 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI Philadelphia on stone: commercial lithography in Philadelphia, 1828-1878 SO EARLY POPULAR VISUAL CULTURE LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1746-0654 EI 1746-0662 J9 EARLY POPUL VIS CULT JI Early Popul. Vis. Cult. PY 2014 VL 12 IS 2 SI SI BP 276 EP 278 DI 10.1080/17460654.2014.891299 PG 5 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA AO2JJ UT WOS:000341146900010 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI Education in the school of dreams: travelogues and early nonfiction film SO EARLY POPULAR VISUAL CULTURE LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1746-0654 EI 1746-0662 J9 EARLY POPUL VIS CULT JI Early Popul. Vis. Cult. PY 2014 VL 12 IS 2 SI SI BP 278 EP 280 DI 10.1080/17460654.2014.891300 PG 5 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA AO2JJ UT WOS:000341146900011 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI The first panoramas: Visions of British imperialism SO EARLY POPULAR VISUAL CULTURE LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1746-0654 EI 1746-0662 J9 EARLY POPUL VIS CULT JI Early Popul. Vis. Cult. PY 2014 VL 12 IS 3 BP 392 EP 393 DI 10.1080/17460654.2014.929775 PG 2 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA AO2JL UT WOS:000341147200006 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI Photography and the American Civil War SO EARLY POPULAR VISUAL CULTURE LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1746-0654 EI 1746-0662 J9 EARLY POPUL VIS CULT JI Early Popul. Vis. Cult. PY 2014 VL 12 IS 3 BP 393 EP 395 DI 10.1080/17460654.2014.929777 PG 4 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA AO2JL UT WOS:000341147200007 ER PT J AU Daskalakis, NP Yehuda, R AF Daskalakis, Nikolaos P. Yehuda, Rachel TI Principles for developing animal models of military PTSD SO EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY LA English DT Article DE Animal; posttraumatic stress disorder; military; combat; biomarkers ID POSTTRAUMATIC-STRESS-DISORDER; SOCIAL DEFEAT STRESS; TRAUMATIC STRESS; AGGRESSION; EXPOSURE; BRAIN; FEAR; HIPPOCAMPUS; RESILIENCE; BIOMARKERS AB The extent to which animal studies can be relevant to military posttraumatic stress disorder (PTSD) continues to be a matter of discussion. Some features of the clinical syndrome are more easily modeled than others. In the animal literature, a great deal of attention is focused on modeling the characteristics of military exposures and their impact on measurable behaviors and biological parameters. There are many issues to consider regarding the ecological validity of predator, social defeat or immobilization stress to combat-related experience. In contrast, less attention has been paid to individual variation following these exposures. Such variation is critical to understand how individual differences in the response to military trauma exposure may result to PTSD or resilience. It is important to consider potential differences in biological findings when comparing extremely exposed to non-exposed animals, versus those that result from examining individual differences. Animal models of military PTSD are also critical in advancing efforts in clinical treatment. In an ideal translational approach to study deployment related outcomes, information from humans and animals, blood and brain, should be carefully considered in tandem, possibly even computed simultaneously, to identify molecules, pathways and networks that are likely to be the key drivers of military PTSD symptoms. With the use novel biological methodologies (e. g., optogenetics) in the animal models, critical genes and pathways can be tuned up or down (rather than over-expressed or ablated completely) in discrete brain regions. Such techniques together with pre-and post-deployment human imaging will accelerate the identification of novel pharmacological and non-pharmacological intervention strategies. C1 [Daskalakis, Nikolaos P.; Yehuda, Rachel] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Daskalakis, Nikolaos P.; Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Mental Hlth Care Ctr, Bronx, NY USA. RP Daskalakis, NP (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, One Gustave L Levy Pl,Box 1668, New York, NY 10029 USA. EM Nikolaos.Daskalakis@mssm.edu RI Daskalakis, Nikolaos/B-7930-2014 OI Daskalakis, Nikolaos/0000-0003-1660-9112 NR 50 TC 8 Z9 9 U1 1 U2 8 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-8066 J9 EUR J PSYCHOTRAUMATO JI Eur. J. Psychotraumatol. PY 2014 VL 5 AR 23825 DI 10.3402/ejpt.v5.23825 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AO2HI UT WOS:000341139000001 ER PT J AU Ivanov, I Yehuda, R AF Ivanov, Iliyan Yehuda, Rachel TI Optimizing fitness for duty and post-combat clinical services for military personnel and combat veterans with ADHD-a systematic review of the current literature SO EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY LA English DT Review DE ADHD; military; PTSD ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY DISORDER; POSTTRAUMATIC-STRESS-DISORDER; PREFRONTAL CORTEX; PSYCHIATRIC-DISORDERS; ADULT ADHD; FOLLOW-UP; CHILDREN; ABNORMALITIES; ADOLESCENTS AB Background: Attention deficit hyper activity disorder (ADHD) is a developmental disorder, most often diagnosed in childhood, and characterized by hyperactivity and inattention that negatively impacts one's ability to function and fulfill social and personal obligations. Individuals with past history of ADHD may enlist in the military under certain conditions, however the full impact of military training and deployment of later in life ADHD symptoms is unclear. It is of particular interest how military experience may affect ADHD in remission and if such individuals might be at elevated risk for relapse of ADHD symptoms. Method: We performed a systematic review f the available literature including the Department of Defense (DOD) guidelines for both eligibility to enlist and fitness for deployment based on reported history and current symptomatology of ADHD. Results: The after care for veterans with ADHD relapse is inconsistent and presents with number of challenges. We evaluate the DOD policies regarding the implications of ADHD for fitness for military service and post-combat mental health. Conclusion: The full extend of the interaction between pre-existing ADHD and post-combat PTSD are not fully understood. The development of comprehensive and clear algorithms for diagnosing and treating ADHD in the military before and after deployment will have a strong positive impact on the quality of care delivered to soldiers and veterans. C1 [Ivanov, Iliyan] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Yehuda, Rachel] James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY USA. RP Ivanov, I (reprint author), Mt Sinai Med Ctr, Dept Psychiat, One Gustave L,Levy Pl,Box 1230, New York, NY 10029 USA. EM iliyan.ivanov@mssm.edu NR 52 TC 3 Z9 3 U1 1 U2 4 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-8066 J9 EUR J PSYCHOTRAUMATO JI Eur. J. Psychotraumatol. PY 2014 VL 5 AR 23894 DI 10.3402/ejpt.v5.23894 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AO2HN UT WOS:000341139600001 ER PT J AU Lehrner, A Yehuda, R AF Lehrner, Amy Yehuda, Rachel TI PTSD IN THE MILITARY: PREVALENCE, PATHOPHYSIOLOGY, TREATMENT Biomarkers of PTSD: military applications and considerations SO EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY LA English DT Article DE Posttraumatic stress disorder; biomarkers; clinical utility; ethics; translation ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN-INJURY; COGNITIVE-BEHAVIORAL THERAPY; PREDICTS TREATMENT RESPONSE; LATENT CLASS ANALYSIS; EXTREME STRESS; ANTERIOR CINGULATE; DISSOCIATIVE-SUBTYPE; ALZHEIMERS-DISEASE; MAJOR DEPRESSION AB Background: Although there are no established biomarkers for posttraumatic stress disorder (PTSD) as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk for PTSD following trauma exposure, and predict or identify recovery. While there has been much interest in PTSD biomarkers, there has been less discussion of their potential clinical applications, and of the social, legal, and ethical implications of such biomarkers. Objective: This article will discuss possible applications of PTSD biomarkers, including the social, legal, and ethical implications of such biomarkers, with an emphasis on military applications. Method: Literature on applications of PTSD biomarkers and on potential ethical and legal implications will be reviewed. Results: Biologically informed research findings hold promise for prevention, assessment, treatment planning, and the development of prophylactic and treatment interventions. As with any biological indicator of disorder, there are potentially positive and negative clinical, social, legal, and ethical consequences of using such biomarkers. Conclusions: Potential clinical applications of PTSD biomarkers hold promise for clinicians, patients, and employers. The search for biomarkers of PTSD should occur in tandem with an interdisciplinary discussion regarding the potential implications of applying biological findings in clinical and employment settings. C1 [Lehrner, Amy; Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Yehuda, Rachel] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Yehuda, Rachel] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. RP Lehrner, A (reprint author), James J Peters Vet Affairs Med Ctr, Mental Hlth Patient Care Ctr, 526 OOMH PTSD 116-A,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM amy.lehrner@va.gov NR 74 TC 10 Z9 10 U1 3 U2 13 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-8066 J9 EUR J PSYCHOTRAUMATO JI Eur. J. Psychotraumatol. PY 2014 VL 5 AR 23797 DI 10.3402/ejpt.v5.23797 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AO2HF UT WOS:000341138600001 ER PT J AU Neylan, TC Schadt, EE Yehuda, R AF Neylan, Thomas C. Schadt, Eric E. Yehuda, Rachel TI Biomarkers for combat-related PTSD: focus on molecular networks from high-dimensional data SO EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY LA English DT Article DE PTSD; genomics; gene expression; proteomics; Computational Biology; risk factors ID POSTTRAUMATIC-STRESS-DISORDER; PLURIPOTENT STEM-CELLS; GENE-EXPRESSION; ALZHEIMERS-DISEASE; SCHIZOPHRENIA; SUSCEPTIBILITY; OBESITY; SYSTEMS; MOUSE; LOCI AB Posttraumatic stress disorder (PTSD) and other deployment-related outcomes originate from a complex interplay between constellations of changes in DNA, environmental traumatic exposures, and other biological risk factors. These factors affect not only individual genes or bio-molecules but also the entire biological networks that in turn increase or decrease the risk of illness or affect illness severity. This review focuses on recent developments in the field of systems biology which use multidimensional data to discover biological networks affected by combat exposure and post-deployment disease states. By integrating large-scale, high-dimensional molecular, physiological, clinical, and behavioral data, the molecular networks that directly respond to perturbations that can lead to PTSD can be identified and causally associated with PTSD, providing a path to identify key drivers. Reprogrammed neural progenitor cells from fibroblasts from PTSD patients could be established as an in vitro assay for high throughput screening of approved drugs to determine which drugs reverse the abnormal expression of the pathogenic biomarkers or neuronal properties. C1 [Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Neylan, Thomas C.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [Schadt, Eric E.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY USA. [Yehuda, Rachel] Mt Sinai Sch Med, Dept Psychiat & Neurobiol, New York, NY USA. RP Neylan, TC (reprint author), VAMC 116P,4150 Clement St, San Francisco, CA 94121 USA. EM Thomas.Neylan@ucsf.edu NR 63 TC 4 Z9 4 U1 0 U2 8 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-8066 J9 EUR J PSYCHOTRAUMATO JI Eur. J. Psychotraumatol. PY 2014 VL 5 AR 23938 DI 10.3402/ejpt.v5.23938 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AO4PW UT WOS:000341323900001 ER PT J AU Yehuda, R Vermetten, E McFarlane, AC Lehrner, A AF Yehuda, Rachel Vermetten, Eric McFarlane, Alexander C. Lehrner, Amy TI PTSD in the military: special considerations for understanding prevalence, pathophysiology and treatment following deployment SO EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY LA English DT Editorial Material DE posttraumatic stress disorder; combat; military; deployment; prevalence; treatment; biomarkers ID PERSONNEL; IRAQ AB Given the unique context of warzone engagement, which may include chronic threat, multiple and lengthy deployments, and loss, there is a need to understand whether and to what extent knowledge about PTSD derived from studies of civilian trauma exposure is generalizeable to the military. This special issue on PTSD in the military addresses a range of issues and debates related to mental health in military personnel and combat veterans. This article provides an overview of the issues covered in selected contributions that have been assembled for a special volume to consider issues unique to the military. Several leading scholars and military experts have contributed papers regarding: 1) prevalence rates of PTSD and other post-deployment mental health problems in different NATO countries, 2) the search for biomarkers of PTSD and the potential applications of such findings, and 3) prevention and intervention approaches for service members and veterans. The volume includes studies that highlight the divergence in prevalence rates of PTSD and other post-deployment mental health problems across nations and that discuss potential causes and implications. Included studies also provide an overview of research conducted in military or Veteran's Affairs settings, and overarching reviews of military-wide approaches to research, promotion of resilience, and mental health interventions in the Unites States and across NATO and allied ISAF partners. C1 [Yehuda, Rachel; Lehrner, Amy] James J Peters Vet Affairs Med Ctr, New York, NY USA. [Yehuda, Rachel] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Vermetten, Eric] Leiden Univ Med Ctr, Dept Psychiat, Leiden, Netherlands. [Vermetten, Eric] Arq Psychotrauma Expert Grp, Diemen, Netherlands. [Vermetten, Eric] Mil Mental Hlth Res, Dept Def, Utrecht, Netherlands. [McFarlane, Alexander C.] Univ Adelaide, Ctr Traumat Stress Studies, Adelaide, SA, Australia. RP Yehuda, R (reprint author), James J Peters Vet Affairs Med Ctr, 526 OOMH PTSD 116-A,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM Rachel.Yehuda@va.gov NR 20 TC 3 Z9 3 U1 1 U2 12 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-8066 J9 EUR J PSYCHOTRAUMATO JI Eur. J. Psychotraumatol. PY 2014 VL 5 AR 25322 DI 10.3402/ejpt.v5.25322 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AO2HS UT WOS:000341140400001 ER PT J AU Hutchinson, JN Fagerness, J Kirby, A Reynolds, R Zak, A Gimelbrant, A Plenge, R Daly, M Chess, A Seddon, JM AF Hutchinson, John N. Fagerness, Jes Kirby, Andrew Reynolds, Robyn Zak, Alex Gimelbrant, Alexander Plenge, Robert Daly, Mark Chess, Andrew Seddon, Johanna M. TI (Epi)Genetic Analyses of Age-Related Macular Degeneration: Case-Control and Discordant Twin Studies SO HUMAN HEREDITY LA English DT Article DE Allele-specific methylation; Age-related macular degeneration; Copy number variation; Epigenetic analysis; Monozygotic twin pairs ID COMPLEMENT FACTOR-H; PERIPHERAL-BLOOD LEUKOCYTES; DNA METHYLATION; MONOZYGOTIC TWINS; HUMAN GENOME; GENE-EXPRESSION; IL17RC PROMOTER; US TWIN; RISK; POLYMORPHISM AB Background/Aims: Phenotypic discordance in monozygotic (MZ) twin pairs can have an epigenetic or genetic basis. Although age-related macular degeneration (AMD) has a strong genetic component, few studies have addressed its epigenetic basis. Methods: Using SNP arrays, we evaluated differences in copy number variation (CNV) and allele-specific methylation (ASM) patterns (via methyl-sensitive restriction enzyme digestion of DNA) in MZ twin pairs from the US Twin Study of AMD. Further analyses examined the relationship between ASM and CNVs with AMD by both case/control analysis of ASM at candidate regions and by analysis of ASM and CNVs in twins discordant for AMD. Results: The frequency of ASM sites differs between cases and controls in regions surrounding the AMD candidate genes CFH, C2 and CFB. While ASM patterns show a substantial dependence on local sequence polymorphisms, we observed dissimilar patterns of ASM between MZ twins. The genes closest to the sites where discordant MZ twins have dissimilar patterns of ASM are enriched for genes implicated in gliosis, a process associated with neovascular AMD. Similar twin-based analyses revealed no AMD-associated CNVs. Conclusions: Our results provide evidence of epigenetic influences beyond the known genetic susceptibility and implicate inflammatory responses and gliosis in the etiology of AMD. (C) 2014 S. Karger AG, Basel C1 [Hutchinson, John N.; Fagerness, Jes; Kirby, Andrew; Daly, Mark; Chess, Andrew] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Reynolds, Robyn; Seddon, Johanna M.] Tufts Med Ctr, New England Eye Ctr, Ophthalm Epidemiol & Genet Serv, Boston, MA 02111 USA. [Zak, Alex; Gimelbrant, Alexander] Harvard Univ, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Gimelbrant, Alexander] Harvard Univ, Harvard Med Sch, Dept Genet, Boston, MA 02115 USA. [Plenge, Robert] Harvard Univ, Brigham & Womens Hosp, Dept Rheumatol Immunol, Boston, MA 02115 USA. [Plenge, Robert] Harvard Univ, Harvard Med Sch, Boston, MA 02115 USA. [Chess, Andrew] Mt Sinai Sch Med, Dept Genet & Genom Sci, Fishberg Dept Neurosci, Dept Dev & Regenerat Biol, New York, NY 10029 USA. [Chess, Andrew] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY 10029 USA. [Seddon, Johanna M.] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. [Seddon, Johanna M.] Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA. RP Chess, A (reprint author), Tufts Med Ctr, 800 Washington St 450, Boston, MA 02111 USA. EM andrew.chess@mssm.edu; jseddon@tuftsmedicalcenter.org FU National Institutes of Health, Bethesda, Md [R01-EY11309]; Massachusetts Lions Eye Research Fund, Inc; Research to Prevent Blindness, Inc., New York, N.Y; American Macular Degeneration Foundation, Northampton, Mass; Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center, Tufts University School of Medicine, Boston, Mass FX We thank Yi Yu and Lillian Merriam for their constructive criticism of the manuscript. This work was supported in part by grants R01-EY11309 from the National Institutes of Health, Bethesda, Md.; Massachusetts Lions Eye Research Fund, Inc.; unrestricted grant from Research to Prevent Blindness, Inc., New York, N.Y.; the American Macular Degeneration Foundation, Northampton, Mass.; donations to the Macular Degeneration Research Fund of the Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center, Tufts University School of Medicine, Boston, Mass. NR 65 TC 2 Z9 2 U1 0 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 EI 1423-0062 J9 HUM HERED JI Hum. Hered. PY 2014 VL 78 IS 2 BP 59 EP 72 DI 10.1159/000362814 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA AN7WW UT WOS:000340812700001 PM 25033836 ER PT J AU Chen, H Meigs, JB Dupuis, J AF Chen, Han Meigs, James B. Dupuis, Josee TI Incorporating Gene-Environment Interaction in Testing for Association with Rare Genetic Variants SO HUMAN HEREDITY LA English DT Article DE Rare variant analysis; Gene-environment interaction; Sequence kernel association test; Joint test; Generalized linear mixed model ID GENERALIZED LINEAR-MODELS; GENOME-WIDE; NORMAL VARIABLES; QUADRATIC-FORMS; COMMON DISEASES; MIXED MODELS; REGRESSION; METAANALYSIS AB Objectives: The incorporation of gene-environment interactions could improve the ability to detect genetic associations with complex traits. For common genetic variants, single-marker interaction tests and joint tests of genetic main effects and gene-environment interaction have been well-established and used to identify novel association loci for complex diseases and continuous traits. For rare genetic variants, however, single-marker tests are severely underpowered due to the low minor allele frequency, and only a few gene-environment interaction tests have been developed. We aimed at developing powerful and computationally efficient tests for gene-environment interaction with rare variants. Methods: In this paper, we propose interaction and joint tests for testing gene-environment interaction of rare genetic variants. Our approach is a generalization of existing gene-environment interaction tests for multiple genetic variants under certain conditions. Results: We show in our simulation studies that our interaction and joint tests have correct type I errors, and that the joint test is a powerful approach for testing genetic association, allowing for gene-environment interaction. We also illustrate our approach in a real data example from the Framingham Heart Study. Conclusion: Our approach can be applied to both binary and continuous traits, it is powerful and computationally efficient. (C) 2014 S. Karger AG, Basel C1 [Chen, Han; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Chen, Han] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. [Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Dupuis, J (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, 801 Massachusetts Ave,3rd Floor, Boston, MA 02118 USA. EM dupuis@bu.edu OI Chen, Han/0000-0002-9510-4923 FU NIH [R01 DK078616, U01 DK85526, K24 DK080140]; National Heart, Lung, and Blood Institute (NHLBI); Boston University [N01-HC-25195]; Affymetrix, Inc. [N02-HL-6-4278] FX The authors would like to thank Dr. Xinyi Lin for sharing the R package iSKAT to perform GESAT-W. This research was partially supported by NIH awards R01 DK078616, U01 DK85526, and K24 DK080140. A portion of this research was conducted using the Linux Clusters for Genetic Analysis (LinGA) computing resources at Boston University Medicine Campus. The Framingham Heart Study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (contract No. N01-HC-25195). This work was partially supported by a contract with Affymetrix, Inc. for genotyping services (contract No. N02-HL-6-4278). NR 29 TC 1 Z9 1 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 EI 1423-0062 J9 HUM HERED JI Hum. Hered. PY 2014 VL 78 IS 2 BP 81 EP 90 DI 10.1159/000363347 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA AN7WW UT WOS:000340812700003 PM 25060534 ER PT S AU Adamia, S Kriangkum, J Belch, AR Pilarski, LM AF Adamia, Sophia Kriangkum, Jitra Belch, Andrew R. Pilarski, Linda M. BE Simpson, MA Heldin, P TI Aberrant Posttranscriptional Processing of Hyaluronan Synthase 1 in Malignant Transformation and Tumor Progression SO HYALURONAN SIGNALING AND TURNOVER SE Advances in Cancer Research LA English DT Review; Book Chapter ID COMPARATIVE GENOMIC HYBRIDIZATION; MEDIATED MOTILITY RHAMM; BREAST-CANCER CELLS; MULTIPLE-MYELOMA; RECEPTOR RHAMM; B-CELLS; CHROMOSOMAL INSTABILITY; COLORECTAL-CANCER; PLASMA-CELLS; WALDENSTROMS MACROGLOBULINEMIA AB It is becoming increasingly apparent that splicing defects play a key role in cancer, and that alterations in genomic splicing elements promote aberrant splicing. Alternative splicing increases the diversity of the human transcriptome and increases the numbers of functional gene products. However, dysregulation that leads to aberrant pre-mRNA splicing can contribute to cancer. Hyaluronan (HA), known to be an important component of cancer progression, is synthesized by hyaluronan synthases (HASs). In cancer cells, hyaluronan synthase 1 (HAS1) pre-mRNA is abnormally spliced to generate a family of aberrant splice variants (HAS1Vs) that synthesize extracellular and intracellular HA. HAS1Vs are clinically relevant, being found almost exclusively in malignant cells. Expression of aberrant HAS1Vs predicts. poor survival in multiple myeloma. In this review, we summarize the unusual properties of HAS1Vs and their relationship to cancer. HAS1Vs form heterogeneous multimers with normally spliced HAS1 as well as with each other and with HAS3. Aberrant variants of HAS1 synthesize HA. Extracellular HA synthesized by HAS1Vs is likely to promote malignant spread. We speculate that synthesis of intracellular HA plays a fundamental and early role in oncogenesis by promoting genetic instability and the emergence of viable cancer variants that lead to aggressive disease. C1 [Adamia, Sophia] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kriangkum, Jitra; Belch, Andrew R.; Pilarski, Linda M.] Univ Alberta, Dept Oncol, Edmonton, AB, Canada. [Kriangkum, Jitra; Belch, Andrew R.; Pilarski, Linda M.] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. RP Adamia, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM sophia_adamia@dfci.harvard.edu NR 88 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-230X BN 978-0-12-800092-2 J9 ADV CANCER RES JI Adv.Cancer Res. PY 2014 VL 123 BP 67 EP 94 DI 10.1016/B978-0-12-800092-2.00003-4 PG 28 WC Oncology SC Oncology GA BB0PE UT WOS:000340575400004 PM 25081526 ER PT J AU Roy, K Pepin, LC Philiossaint, M Lorius, N Becker, JA Locascio, JJ Rentz, DM Sperling, RA Johnson, KA Marshall, GA AF Roy, Kamolika Pepin, Lesley C. Philiossaint, Marlie Lorius, Natacha Becker, J. Alex Locascio, Joseph J. Rentz, Dorene M. Sperling, Reisa A. Johnson, Keith A. Marshall, Gad A. CA Alzheimer's Dis Neuroimaging Initi TI Regional Fluorodeoxyglucose Metabolism and Instrumental Activities of Daily Living across the Alzheimer's Disease Spectrum SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE F-18-fluorodeoxyglucose positron emission tomography; Alzheimer's disease; instrumental activities of daily living; mild cognitive impairment ID MILD COGNITIVE IMPAIRMENT; DEMENTIA; SCHIZOPHRENIA; TIME; PET AB Background: Impairment in instrumental activities of daily living (IADL) begins as individuals with amnestic mild cognitive impairment (MCI) transition to Alzheimer's disease (AD) dementia. IADL impairment in AD dementia has been associated with inferior parietal, inferior temporal, and superior occipital hypometabolism using F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET). Objective: To investigate the relationship between regional FDG metabolism and IADL in clinically normal (CN) elderly, MCI, and mild AD dementia subjects cross-sectionally and longitudinally. Methods: One hundred and four CN, 203 MCI, and 95 AD dementia subjects from the Alzheimer's Disease Neuroimaging Initiative underwent clinical assessments every 6 to 12 months for up to three years and baseline FDG PET. The subjective, informant-based Functional Activities Questionnaire was used to assess IADL. General linear models and mixed effects models were used, covarying for demographics, cognition, and behavior. Results: The cross-sectional analysis revealed middle frontal and orbitofrontal hypometabolism were significantly associated with greater IADL impairment. Additionally, the interaction of diagnosis with posterior cingulate and with parahippocampal hypometabolism showed a greater decline in IADL performance as metabolism decreased for the AD dementia relative to the MCI group, and the MCI group relative to the CN group. The longitudinal analysis showed that baseline middle frontal and posterior cingulate hypometabolism were significantly associated with greater rate of increase in IADL impairment over time. Conclusion: These results suggest that regional synaptic dysfunction, including the Alzheimer-typical medial parietal and less typical frontal regions, relates to daily functioning decline at baseline and over time across the early AD spectrum. C1 [Roy, Kamolika; Lorius, Natacha; Rentz, Dorene M.; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Roy, Kamolika; Lorius, Natacha; Rentz, Dorene M.; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Roy, Kamolika; Lorius, Natacha; Locascio, Joseph J.; Rentz, Dorene M.; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Pepin, Lesley C.; Philiossaint, Marlie; Becker, J. Alex; Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Marshall, GA (reprint author), Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, 221 Longwood Ave,BL-104H, Boston, MA 02115 USA. EM gamarshall@partners.org FU Massachusetts Alzheimer's Disease Research Center [P50 AG005134]; Harvard Aging Brain Study [P01 AGO36694]; Alzheimer's Disease Neuroimaging Initiative (ADNI) (NIH Grant) [U01 AG024904]; Janssen Alzheimer Immunotherapy; Wyeth/Pfizer Pharmaceuticals; Bristol-Myers-Squibb; [R01 AG027435]; [K23 AG033634]; [K24 AG035007] FX This study was supported by R01 AG027435, K23 AG033634, K24 AG035007, the Massachusetts Alzheimer's Disease Research Center (P50 AG005134), the Harvard Aging Brain Study (P01 AGO36694), and the Alzheimer's Disease Neuroimaging Initiative (ADNI) (NIH Grant U01 AG024904) (See Supplementary Material). Drs. Keith Johnson and Alex Becker at the Department of Radiology, MGH; David Kennedy and Christian Haselgrove at the Centre for Morphometric Analysis, Harvard; Bruce Fischl, Martinos Center for Biomedical Imaging, MGH; Janis Breeze and Jean Frazier, Child and Adolescent Neuropsychiatric Research Program, Cambridge Health Alliance; Larry Seidman and Jill Goldstein, Department of Psychiatry of Harvard Medical School; Barry Kosofsky, Weill Cornell Medical Center.; The authors have received research salary support from Janssen Alzheimer Immunotherapy (DMR and GAM), Wyeth/Pfizer Pharmaceuticals (DMR and GAM), and Bristol-Myers-Squibb (RAS). NR 35 TC 6 Z9 6 U1 2 U2 6 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2014 VL 42 IS 1 BP 291 EP 300 DI 10.3233/JAD-131796 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AN3KS UT WOS:000340487200021 PM 24898635 ER PT J AU Bakker, JP Edwards, BA Gautam, SP Montesi, SB Duran-Cantolla, J Aizpuru, F Barbe, F Sanchez-de-la-Torre, M Malhotra, A AF Bakker, Jessie P. Edwards, Bradley A. Gautam, Shiva P. Montesi, Sydney B. Duran-Cantolla, Joaquin Aizpuru, Felipe Barbe, Ferran Sanchez-de-la-Torre, Manuel Malhotra, Atul TI Blood Pressure Improvement with Continuous Positive Airway Pressure is Independent of Obstructive Sleep Apnea Severity SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE Patient-level meta-analysis; hypertension; obstructive sleep apnea; positive airway pressure; lung ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; HYPOPNEA SYNDROME; CPAP; HYPERTENSION; METAANALYSIS; THERAPY; OXYGEN; MALES; OSA AB Study Objectives: We sought to perform a patient-level meta-analysis using the individual patient data of the trials identified in our previous study-level meta-analysis investigating the effect of positive airway pressure (PAP) treatment for obstructive sleep apnea (OSA) on blood pressure (BP). Design: Patient-level meta-analysis. Setting: N/A. Participants: 968 adult OSA subjects without major comorbidities drawn from eight randomized controlled trials. Interventions: Therapeutic PAP versus non-therapeutic control conditions (sham-PAP, pill placebo or standard care) over at least one week. Measurements and Results: The mean reductions in BP between PAP and non-therapeutic control arms were -2.27 mm Hg (95% CI -4.01 to -0.54) for systolic BP and -1.78 mm Hg (95% CI -2.99 to -0.58) for diastolic BP. The presence of uncontrolled hypertension at baseline was significantly associated with a reduction in systolic BP of 7.1 mm Hg and diastolic BP of 4.3 mm Hg after controlling for OSA severity (apnea-hypopnea index, Epworth Sleepiness Scale score, PAP level), patient demographics (age, gender, body mass index, use of antihypertensive medication/s), and measures of PAP efficacy (PAP adherence and treatment duration). Conclusions: OSA patients with uncontrolled hypertension are likely to gain the largest benefit from PAP in terms of a substantial reduction in BP, even after controlling for disease severity. C1 [Bakker, Jessie P.; Edwards, Bradley A.; Malhotra, Atul] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Bakker, Jessie P.; Edwards, Bradley A.; Gautam, Shiva P.; Malhotra, Atul] Harvard Univ, Sch Med, Boston, MA USA. [Gautam, Shiva P.] Beth Israel Deaconess Med Ctr, Div Translat Res, Boston, MA 02215 USA. [Montesi, Sydney B.; Malhotra, Atul] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Duran-Cantolla, Joaquin; Aizpuru, Felipe] Univ Basque Country, Araba Univ, Sleep Div, Res Dept, Vitoria, Spain. [Barbe, Ferran; Sanchez-de-la-Torre, Manuel] Hosp Arnau Vilanova, IRB Lleida, Resp Dept, Lleida, Spain. [Barbe, Ferran; Sanchez-de-la-Torre, Manuel] CIBERes, Madrid, Spain. RP Bakker, JP (reprint author), Sleep Disorders Res Program, 221 Longwood Ave 036BLI, Boston, MA 02115 USA. EM jpbakker@partners.org RI Sanchez de la Torre, Manuel/B-5578-2009; Duran Cantolla, Joaquin/B-6996-2015; Barbe, Ferran/A-5988-2010; OI Sanchez de la Torre, Manuel/0000-0002-5695-348X; Barbe, Ferran/0000-0002-2340-8928; Edwards, Bradley/0000-0001-9383-1644 FU Harvard Catalyst, the Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health) [8UL1TR000170-05]; Harvard University; NIH [R01HL110350, R01HL085188, R01HL090897, K24HL093218, P01HL095491]; National Health and Medical Research Council of Australia's CJ Martin Overseas Biomedical Fellowship [1035115]; AHA [0840159N]; Instituto de Salud Carlos III (Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo, Spain) [PI 04/0165, PI10/02763] FX We thank the authors of original trials who provided individual patient data for these analyses. This work was conducted with support from Harvard Catalyst, the Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05 and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health. Dr. Bakker is supported by NIH R01HL110350. Dr. Edwards is supported by the National Health and Medical Research Council of Australia's CJ Martin Overseas Biomedical Fellowship (1035115). Dr. Malhotra is supported by NIH (R01HL110350, R01HL085188, R01HL090897, K24HL093218, P01HL095491) and AHA (0840159N) grants. Dr. Barb is supported by Instituto de Salud Carlos III (PI 04/0165 and PI10/02763) (Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo, Spain) grant. No financial support was obtained for this investigation. NR 38 TC 19 Z9 19 U1 0 U2 3 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 EI 1550-9397 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2014 VL 10 IS 4 BP 365 EP 369 DI 10.5664/jcsm.3604 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA AO2GC UT WOS:000341134500003 PM 24733980 ER PT J AU Walia, HK Li, H Rueschman, M Bhatt, DL Patel, SR Quan, SF Gottlieb, DJ Punjabi, NM Redline, S Mehra, R AF Walia, Harneet K. Li, Hong Rueschman, Michael Bhatt, Deepak L. Patel, Sanjay R. Quan, Stuart F. Gottlieb, Daniel J. Punjabi, Naresh M. Redline, Susan Mehra, Reena TI Association of Severe Obstructive Sleep Apnea and Elevated Blood Pressure Despite Antihypertensive Medication Use SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE sleep apnea; blood pressure; cardiovascular disease ID RESISTANT HYPERTENSION; CARDIOVASCULAR-DISEASE; SYSTOLIC HYPERTENSION; RISK STRATIFICATION; HEART-FAILURE; ALDOSTERONE; PROGRESSION; MECHANISMS; PREVENTION; DAMAGE AB Rationale: We hypothesized that untreated severe obstructive sleep apnea (OSA) is associated with elevated ambulatory blood pressure (BP) in subjects with high cardiovascular disease (CVD) risk despite medical management. Methods: Data from the baseline examination of the Heart Biomarker Evaluation in Apnea Treatment (HeartBEAT) study, a 4-site randomized controlled trial were analyzed. Individuals with moderate-severe OSA (apnea hypopnea index, AHI = 15-50) and cardiovascular risk were recruited from cardiology practices. Those with hypertension were included. Intensive antihypertensive regimen (IAR) was defined as >= 3 antihypertensives including a diuretic. Definitions were: controlled BP (BP < 130/80), uncontrolled elevated BP (BP >= 130/80 not on IAR) and resistant elevated BP (BP >= 130/80 mm Hg despite IAR). Associations of untreated severe OSA (AHI >= 30) and uncontrolled and resistant elevated BP were evaluated using logistic regression analyses adjusted for age, sex, race, body mass index, smoking status, diabetes, and CVD. Results: Among the 284 participants (mean age 63.1 +/- 7.2 years, 23.6% with severe OSA), 61.6% had controlled BP, 28.5% had uncontrolled elevated BP, and 9.9% had resistant elevated BP. Among participants prescribed IAR, resistant elevated BP was more prevalent in those with severe compared to moderate OSA (58.3% vs. 28.6%, p = 0.01). Participants with severe OSA had a 4-fold higher adjusted odds of resistant elevated BP (OR 4.1, 95% CI: 1.7-10.2), a fi nding not reproduced in the absence of IAR use. Conclusions: Among patients with increased cardiovascular risk and moderate to severe OSA, untreated severe compared to moderate OSA was associated with elevated BP despite IAR suggesting untreated severe OSA contributes to poor BP control despite aggressive medication use. Commentary: A commentary on this article appears in this issue on page 845. C1 [Walia, Harneet K.; Mehra, Reena] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. [Li, Hong] Case Western Reserve Univ, Ctr Clin Invest, Cleveland, OH 44106 USA. [Rueschman, Michael; Patel, Sanjay R.; Quan, Stuart F.; Gottlieb, Daniel J.; Redline, Susan] Brigham & Womens Hosp, Boston, MA 02115 USA. [Patel, Sanjay R.; Redline, Susan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Gottlieb, Daniel J.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. [Punjabi, Naresh M.] Johns Hopkins Univ, Baltimore, MD USA. [Bhatt, Deepak L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Heart & Vasc Ctr, Boston, MA 02115 USA. RP Walia, HK (reprint author), Cleveland Clin, Ctr Sleep Disorders, 9500 Euclid Ave, Cleveland, OH 44106 USA. EM waliah@ccf.org OI Mehra, Reena/0000-0002-6222-2675; Patel, Sanjay/0000-0002-9142-5172 FU NIH National Heart Lung Blood Institute [RC2 HL101417, NIH M01 RR00080, NIH UL1 RR024989]; National Center for Research Resources (NCRR); NIH NHLBI [1R01HL109493, R21HL108226] FX This study was supported by NIH National Heart Lung Blood Institute RC2 HL101417, NIH M01 RR00080, NIH UL1 RR024989 from the National Center for Research Resources (NCRR). Dr. Mehra was supported by NIH NHLBI 1R01HL109493 and R21HL108226. Dr. Bhatt is on the Advisory Board of Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; is on the Board of Directors of Boston VA Research Institute, and Society of Cardiovascular Patient Care; is chair of American Heart Association Get With The Guidelines Steering Committee; is on the Data Monitoring Committees of Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and Population Health Research Institute; has received honoraria from the American College of Cardiology (Editor, Clinical Trials, Cardiosource), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor in Chief, Journal of Invasive Cardiology), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), and WebMD (CME steering committees); has received research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Roche, Sanofi Aventis, and The Medicines Company; has participated in unfunded research for FlowCo, PLx Pharma, and Takeda. Additional disclosures for Dr. Bhatt are Clinical Cardiology (Associate Editor) and Journal of the American College of Cardiology (Section Editor, Pharmacology). Dr. Mehra serves on the Medical Advisory Board for Care Core National, has received funding from the National Institutes of Health for research and her institution has received positive airway devices from Philips Respironics for research for which she is the Principal Investigator. Dr. Quan is Editor-in-Chief of the Journal of Clinical Sleep Medicine and has served as a consultant for Saatchi and Saatchi. Dr. Patel has served as a consultant to Apnex Medical, Apnicure, and Vertex Pharmaceuticals. His institution, Brigham and Women's Hospital has received grant support and/or equipment for research studies from ResMed Inc, ResMed Foundation, and Philips Respironics. Dr. Gottlieb is a consultant for ResMed Corporation and PI or co-investigator on multiple VA-funded sleep apnea research studies. Dr. Redline is PI for NIH funded research of sleep apnea and cardiac disease, PI of a grant from ResMed, and has received equipment from Philips Respironics and ResMed for research. Dr. Punjabi has received research support from ResMed. The other authors have indicated no financial conflicts of interest. NR 36 TC 14 Z9 14 U1 0 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 EI 1550-9397 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2014 VL 10 IS 8 BP 835 EP 843 DI 10.5664/jcsm.3946 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AO2GS UT WOS:000341136600003 PM 25126027 ER PT J AU Imel, ZE Barco, JS Brown, HJ Baucom, BR Baer, JS Kircher, JC Atkins, DC AF Imel, Zac E. Barco, Jacqueline S. Brown, Halley J. Baucom, Brian R. Baer, John S. Kircher, John C. Atkins, David C. TI The Association of Therapist Empathy and Synchrony in Vocally Encoded Arousal SO JOURNAL OF COUNSELING PSYCHOLOGY LA English DT Article DE empathy; synchrony; speech signal processing ID INTERPERSONAL COMPLEMENTARITY; FUNDAMENTAL-FREQUENCY; SOCIAL-INTERACTION; PSYCHOTHERAPY; MODELS; EXPRESSION; CONFLICT; PATTERNS; LANGUAGE; EMOTION AB Empathy is a critical ingredient in motivational interviewing (MI) and in psychotherapy generally. It is typically defined as the ability to experience and understand the feelings of another. Basic science indicates that empathy is related to the development of synchrony in dyads. However, in clinical research, empathy has proved difficult to operationalize and measure, and has mostly relied on the felt sense of observers, clients, or therapists. We extracted estimates of therapist and standardized patient (SP) vocally encoded arousal (mean fundamental frequency; mean f(0)) in 89 MI sessions with high and low empathy ratings from independent observers. We hypothesized (a) therapist and SP mean f0 would be correlated and (b) the correlation of therapist and SP mean f(0) would be greater in sessions with high empathy as compared with low. On the basis of a multivariate mixed model, the correlation between therapist and SP mean f(0) was large (r = .71) and close to 0 in randomly assigned therapist-SP dyads (r = -.08). The association was higher in sessions with high empathy ratings (r = .80) than in sessions with low ratings (r = .36). There was strong evidence for vocal synchrony in clinical dyads as well as for the association of synchrony with empathy ratings, illustrating the relevance of basic psychological processes to clinical interactions. These findings provide initial evidence for an objective and nonobtrusive method for assessing therapist performance. Novel indicators of therapist empathy may have implications for the study of MI process as well as the training of therapists generally. C1 [Imel, Zac E.; Barco, Jacqueline S.; Brown, Halley J.; Kircher, John C.] Univ Utah, Dept Educ Psychol, Salt Lake City, UT 84112 USA. [Baucom, Brian R.] Univ Utah, Dept Psychol, Salt Lake City, UT 84112 USA. [Baer, John S.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Baer, John S.] VA Puget Sound Healthcare Syst, Seattle Div, Seattle, WA USA. [Atkins, David C.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Imel, ZE (reprint author), Univ Utah, Dept Educ Psychol, Counseling Psychol Program, 1705 Campus Ctr Dr,Room 327, Salt Lake City, UT 84112 USA. EM zac.imel@utah.edu OI imel, zachary/0000-0001-9645-7184; Atkins, David/0000-0002-5781-9880 FU NIAAA NIH HHS [R01 AA018673]; NIDA NIH HHS [R01 DA016360, R34 DA034860] NR 53 TC 12 Z9 12 U1 2 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-0167 EI 1939-2168 J9 J COUNS PSYCHOL JI J. Couns. Psychol. PD JAN PY 2014 VL 61 IS 1 BP 146 EP 153 DI 10.1037/a0034943 PG 8 WC Psychology, Educational; Psychology, Applied SC Psychology GA AO2SF UT WOS:000341175100013 PM 24274679 ER PT J AU Wei, LN Sweeney, AJ Sheng, LY Fang, Y Kindy, MS Xi, TF Gao, BZ AF Wei, Lina Sweeney, Andrew J. Sheng, Liyuan Fang, Yu Kindy, Mark S. Xi, Tingfei Gao, Bruce Z. TI Single-neuron axonal pathfinding under geometric guidance: low-dose-methylmercury developmental neurotoxicity test SO LAB ON A CHIP LA English DT Article ID WHITE-MATTER; IN-VITRO; GROWTH; EXPOSURE; MECHANISMS; OUTGROWTH; CULTURE; BINDING; PIONEER; AUTISM AB Because the nervous system is most vulnerable to toxicants during development, there is a crucial need for a highly sensitive developmental-neurotoxicity-test model to detect potential toxicants at low doses. We developed a lab-on-chip wherein single-neuron axonal pathfinding under geometric guidance was created using soft lithography and laser cell-micropatterning techniques. After coating the surface with L1, an axon-specific member of the Ig family of cell adhesion molecules (CAMs), and optimizing microunit geometric parameters, we introduced low-dose methylmercury, a well-known, environmentally significant neurotoxicant, in the shared medium. Its developmental neurotoxicity was evaluated using a novel axonal pathfinding assay including axonal turning and branching rates at turning points in this model. Compared to the conventional neurite-outgrowth assay, this model's detection threshold for low-dose methylmercury was 10-fold more sensitive at comparable exposure durations. These preliminary results support study of developmental effects of known and potential neurotoxicants on axon pathfinding. This novel assay model would be useful to study neuronal disease mechanisms at the single-cell level. To our knowledge, the potential of methylmercury chloride to cause acute in vitro developmental neurotoxicity (DNT) at such a low dosage has not been reported. This is the first DNT test model with high reproducibility to use single-neuron axonal pathfinding under precise geometric guidance. C1 [Wei, Lina; Xi, Tingfei] Peking Univ, Acad Adv Interdisciplinary Studies, Ctr Biomed Mat & Tissue Engn, Beijing 100871, Peoples R China. [Sweeney, Andrew J.; Kindy, Mark S.; Gao, Bruce Z.] Clemson Univ, Dept Bioengn, Biophoton Lab, Clemson, SC 29634 USA. [Sheng, Liyuan; Xi, Tingfei] Peking Univ, Shenzhen Inst, Key Lab Human Tissue Regenerat & Repair, Shenzhen 518057, Peoples R China. [Fang, Yu] Natl Inst Food & Drug Control, Inst Med Devices Control, Div Standardizat & Sci Res, Beijing 100050, Peoples R China. [Kindy, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29466 USA. [Kindy, Mark S.] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29466 USA. [Kindy, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC 29403 USA. RP Xi, TF (reprint author), Peking Univ, Acad Adv Interdisciplinary Studies, Ctr Biomed Mat & Tissue Engn, Beijing 100871, Peoples R China. EM xitingfei@pku.edu.cn; zgao@clemson.edu RI Sheng, Liyuan/E-2741-2012; OI Sheng, Liyuan/0000-0002-2642-7622 FU National Natural Science Foundation of China [31070847, 31370956]; Strategic New Industry Development Special Foundation of Shenzhen [JCYJ20130402172114948]; Guangdong Provincial Department of Science and Technology, China [2011B050400011]; NIH COBRE grant from NIGMS [NIH P20GM103444] FX The authors would like to thank Dr. Ken Webb for insightful discussion of application of L1. This work was supported by the National Natural Science Foundation of China (no. 31070847, 31370956), Strategic New Industry Development Special Foundation of Shenzhen (no. JCYJ20130402172114948), Guangdong Provincial Department of Science and Technology, China (2011B050400011), and NIH COBRE grant from NIGMS (NIH P20GM103444). NR 33 TC 2 Z9 2 U1 4 U2 19 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 EI 1473-0189 J9 LAB CHIP JI Lab Chip PY 2014 VL 14 IS 18 BP 3564 EP 3571 DI 10.1039/c4lc00723a PG 8 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA AN3GQ UT WOS:000340474300017 PM 25041816 ER PT J AU Valenza, G Citi, L Gentili, C Lanata, A Scilingo, EP Barbieri, R AF Valenza, G. Citi, L. Gentili, C. Lanata, A. Scilingo, E. P. Barbieri, R. TI Point-process Nonlinear Autonomic Assessment of Depressive States in Bipolar Patients SO METHODS OF INFORMATION IN MEDICINE LA English DT Article DE Bipolar Disorder; Heart Rate Variability (HRV); Point Process; High Order Statistics; Bispectrum; Nonlinear Analysis; Wiener-Volterra Series; International Affective Picture System (IAPS); Thematic Apperception Test (TAT) ID HEART-RATE-VARIABILITY AB Introduction: This article is part of the Focus Theme of Methods of Information in Medicine on "Biosignal Interpretation: Advanced Methods for Studying Cardiovascular; and Respiratory Systems". Objectives: The goal of this work is to apply a computational methodology able to characterize mood states in bipolar patients through instantaneous analysis of heartbeat dynamics. Methods: A Point-Process-based Nonlinear Autoregressive Integrative (NARI) model is applied to analyze data collected from five bipolar patients (two males and three females, age 42.4 +/- 10.5 range 32-56) under going a dedicated affective elicitation protocol using images from the International Affective Picture System (IAPS) and Thematic Apperception Test (TAT). The study was designed within the European project PSYCHE (Personalised monitoring SYstems for Care in mental HEalth). Results: Results demonstrate that the inclusion of instantaneous higher order spectral (HOS) features estimated from the NARI nonlinear assessment significantly improves the accuracy in successfully recognizing specific mood states such as euthymia and depression with respect to results using only linear indices. In particular, a specificity of 74.44% using the instantaneous linear features set,, and 99.56% using also the nonlinear feature set were achieved. Moreover, IAPS emotional elicitation resulted in a more discriminant : procedure with respect to the TAT elicitation protocol. Contlusions: A significant pattern of instantaneous heartbeat features was found in; depressive and euthymic states despite the inter-subject variability. The presented point process Heart Rate Variability (HRV) nonlinear methodology provides a promising application in the field of mood assessment in bipolar patients. C1 [Valenza, G.; Citi, L.; Barbieri, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA USA. [Valenza, G.; Citi, L.; Barbieri, R.] MIT, Cambridge, MA 02139 USA. [Valenza, G.; Lanata, A.; Scilingo, E. P.] Univ Pisa, Res Ctr E Piaggio, I-56122 Pisa, Italy. [Gentili, C.] Univ Pisa, Dept Psychiat Neurobiol Pharmacol & Biotechnol, I-56122 Pisa, Italy. [Citi, L.] Univ Essex, Sch Elect Engn & Comp Sci, Colchester CO4 3SQ, Essex, England. RP Valenza, G (reprint author), Univ Pisa, Fac Engn, Dept Informat Engn, Res Ctr E Piaggio, Via G Caruso 16, I-56122 Pisa, Italy. EM g.valenza@ieee.org RI Citi, Luca/G-2270-2011; OI Citi, Luca/0000-0001-8702-5654; Barbieri, Riccardo/0000-0001-9381-3833; Lanata, Antonio/0000-0002-6540-5952; Scilingo, Enzo Pasquale/0000-0003-2588-4917; Gentili, Claudio/0000-0002-2579-8755; Valenza, Gaetano/0000-0001-6574-1879 FU Department of Anesthesia, Critical Care & Pain Medicine, Massachusetts General Hospital; Harvard Medical School, Boston, MA, USA; European Union [601165, 247777] FX The research leading to these results has received partial funding from the Department of Anesthesia, Critical Care & Pain Medicine, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA, and European Union Seventh Framework Programme FP7/2007-2013 under grant agreement n. 601165 of the project "WEARHAP" and under grant agreement ICT-247777 of the project "PSYCHE". NR 24 TC 15 Z9 15 U1 0 U2 4 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2014 VL 53 IS 4 BP 296 EP 302 DI 10.3414/ME13-02-0036 PG 7 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA AN7WC UT WOS:000340810700012 PM 24970591 ER PT J AU Portelius, E Soininen, H Andreasson, U Zetterberg, H Persson, R Karlsson, G Blennow, K Herukka, SK Mattsson, N AF Portelius, Erik Soininen, Hilkka Andreasson, Ulf Zetterberg, Henrik Persson, Rita Karlsson, Goesta Blennow, Kaj Herukka, Sanna-Kaisa Mattsson, Niklas TI Exploring Alzheimer Molecular Pathology in Down's Syndrome Cerebrospinal Fluid SO NEURODEGENERATIVE DISEASES LA English DT Article DE Down's syndrome; Alzheimer's disease; Orexin-A; Amyloid-beta; YKL-40; Tau ID AMYLOID-BETA-PEPTIDE; DISEASE; PROTEIN; DEMENTIA; OREXIN; TAU; INFLAMMATION; DEPOSITION; BRAIN; CDNA AB Background: Individuals with Down's syndrome (DS) develop early Alzheimer's disease (AD) with beta-amyloid (A beta) plaque pathology. The extra amyloid precursor protein (APP) gene copy in DS is believed to result in a 50% increase in A beta production, but it is unclear how this relates to the development of other AD hallmarks, including axonal degeneration and microglia cell activation, and to other neurological problems in DS, including disturbed sleep regulation. Objective: To evaluate if cerebrospinal fluid (CSF) biomarkers for cerebral annyloidosis, axonal degeneration, microglial activation and sleep regulation were altered in young and old patients with DS, and if these biomarkers were related to altered A beta and APP metabolism, reflected by CSF levels of different A beta and APP peptides. Methods: CSF from DS patients (n = 12) and healthy controls (n = 20) were analyzed for A beta peptides (A beta 1-42, A beta X-38/40/42), secreted APP species (sAPP alpha/beta), biomarkers for AD-like axonal degeneration [total tau (T-tau), phosphorylated tau], microglial activation (YKL-40, CC chemokine ligand 2) and orexin-A, which is a peptide involved in sleep regulation. We compared biomarker levels between groups and tested for relations between biomarkers, disease stage and age. Results: Several of the markers were specifically increased in DS, including ABX-40, sAPP alpha and sAPP beta. Orexin-A was significantly decreased in DS and correlated with A beta and sAPP. Orexin-A decreased with age in DS, while T-tau and YKL-40 increased with age. Conclusion: Down's patients have increased APP and A beta production and increased microglial activation with age. The orexin-A metabolism is disturbed in DS and may be linked to APP and A beta production. Bionnarker studies of DS may contribute to our understanding of the annyloidogenic and neurodegenerative process in AD. (C) 2014 S. Karger AG, Basel C1 [Portelius, Erik; Andreasson, Ulf; Zetterberg, Henrik; Persson, Rita; Karlsson, Goesta; Blennow, Kaj; Mattsson, Niklas] Univ Gothenburg, Sahlgrenska Acad, Dept Psychiat & Neurochem, Inst Neurosci & Physiol, Gothenburg, Sweden. [Soininen, Hilkka; Herukka, Sanna-Kaisa] Univ Eastern Finland, Dept Neurol, Kuopio, Finland. [Soininen, Hilkka; Herukka, Sanna-Kaisa] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Zetterberg, Henrik] UCL Inst Neurol, Dept Mol Neurosci, London, England. [Mattsson, Niklas] Univ Calif San Francisco, Ctr Imaging Neurodegenerat Dis, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Mattsson, Niklas] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. RP Portelius, E (reprint author), Sahlgrenska Univ Hosp Molndal, Dept Psychiat & Neurochem, SE-43180 Molndal, Sweden. EM erik.portelius@neuro.gu.se FU Swedish Research Council [14002, K2010-63P-21562-01-4, K2011-61X-20401-05-6]; Knut and Alice Wallenberg Foundation; Stiftelsen Gamla Tjanarinnor; Magn. Bergvalls Stiftelse; Gun och Bertil Stohnes Stiftelse; Swedish Brain Fund; Alzheimer Foundation, Sweden; Dementia Association, Sweden; Wenner-Gren foundation; JPND Project BIOMARKAPD; Goteborgs Lakaresallskap; Svenska Lakaresallskapet; Sahlgrenska Universitetssjukhuset; Carl-Bertil Laurells fond; Klinisk Biokemi i Norden FX This study was supported by the Swedish Research Council (project No. 14002, K2010-63P-21562-01-4, K2011-61X-20401-05-6), the Knut and Alice Wallenberg Foundation, Stiftelsen Gamla Tjanarinnor, Magn. Bergvalls Stiftelse, Gun och Bertil Stohnes Stiftelse, the Swedish Brain Fund, the Alzheimer Foundation, Sweden, the Dementia Association, Sweden, the Wenner-Gren foundation, the JPND Project BIOMARKAPD, Goteborgs Lakaresallskap, Svenska Lakaresallskapet, Sahlgrenska Universitetssjukhuset, Carl-Bertil Laurells fond and Klinisk Biokemi i Norden. NR 47 TC 8 Z9 9 U1 3 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 EI 1660-2862 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2014 VL 14 IS 2 BP 98 EP 106 DI 10.1159/000358800 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AN7WV UT WOS:000340812600005 PM 24992945 ER PT S AU Cho, TA McKendall, RR AF Cho, Tracey A. McKendall, Robert R. BE Tselis, AC Booss, J TI Clinical approach to the syndromes of viral encephalitis, myelitis, and meningitis SO NEUROVIROLOGY SE Handbook of Clinical Neurology LA English DT Article; Book Chapter ID HERPES-SIMPLEX ENCEPHALITIS; CENTRAL-NERVOUS-SYSTEM; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; POLYMERASE-CHAIN-REACTION; ACUTE TRANSVERSE MYELITIS; TICK-BORNE ENCEPHALITIS; OF-THE-LITERATURE; CEREBROSPINAL-FLUID; UNITED-STATES; BACTERIAL-MENINGITIS C1 [Cho, Tracey A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Cho, Tracey A.] Massachusetts Gen Hosp, Neuroid Program, Boston, MA 02114 USA. [McKendall, Robert R.] Univ Texas Med Branch, Dept Neurol, Galveston, TX 77555 USA. [McKendall, Robert R.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. RP McKendall, RR (reprint author), Univ Texas Med Branch, 301 Univ Blvd, Galveston, TX 77555 USA. EM rmckenda@utmb.edu NR 127 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0072-9752 BN 978-0-444-53488-0; 978-0-702-04539-4 J9 HAND CLINIC PY 2014 VL 123 BP 89 EP 121 PG 33 WC Clinical Neurology SC Neurosciences & Neurology GA BB1EM UT WOS:000341048300006 PM 25015482 ER PT S AU Carrithers, MD AF Carrithers, Michael D. BE Tselis, AC Booss, J TI Innate immune viral recognition: relevance to CNS infections SO NEUROVIROLOGY SE Handbook of Clinical Neurology LA English DT Article; Book Chapter ID WEST-NILE-VIRUS; TOLL-LIKE RECEPTORS; DENDRITIC CELLS; RIG-I; ADAPTIVE IMMUNITY; SIGNAL-TRANSDUCTION; MULTIPLE-SCLEROSIS; STRANDED-RNA; HEPATITIS-C; MACROPHAGES C1 [Carrithers, Michael D.] William S Middleton Mem Vet Adm Med Ctr, Neurol Serv, Madison, WI USA. [Carrithers, Michael D.] Univ Wisconsin, Dept Neurol, Madison, WI 53706 USA. RP Carrithers, MD (reprint author), Univ Wisconsin, Dept Neurol, 1300 Univ Ave,Room 2679, Madison, WI 53706 USA. EM carrithers@neurology.wisc.edu NR 62 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0072-9752 BN 978-0-444-53488-0; 978-0-702-04539-4 J9 HAND CLINIC PY 2014 VL 123 BP 215 EP 223 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA BB1EM UT WOS:000341048300011 PM 25015487 ER PT S AU Hill, JA Venna, N AF Hill, Joshua A. Venna, Nagagopal BE Tselis, AC Booss, J TI Human herpesvirus 6 and the nervous system SO NEUROVIROLOGY SE Handbook of Clinical Neurology LA English DT Article; Book Chapter ID STEM-CELL TRANSPLANTATION; POLYMERASE-CHAIN-REACTION; CHRONIC-FATIGUE-SYNDROME; BONE-MARROW-TRANSPLANTATION; MULTIPLE-SCLEROSIS PATIENTS; BLOOD MONONUCLEAR-CELLS; HUMAN-HERPESVIRUS-6 VARIANT-A; EPSTEIN-BARR-VIRUS; REAL-TIME PCR; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY C1 [Hill, Joshua A.] Univ Washington, Div Allergy & Infect Dis, Seattle, WA 98195 USA. [Venna, Nagagopal] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Hill, JA (reprint author), Univ Washington, Div Allergy & Infect Dis, Seattle, WA 98195 USA. EM joshuaah@uw.edu OI HILL, JOSHUA/0000-0002-7665-7100 NR 314 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0072-9752 BN 978-0-444-53488-0; 978-0-702-04539-4 J9 HAND CLINIC PY 2014 VL 123 BP 327 EP 355 PG 29 WC Clinical Neurology SC Neurosciences & Neurology GA BB1EM UT WOS:000341048300018 PM 25015494 ER PT J AU Zhao, F Heesters, BA Chiu, I Gao, Y Shi, JF Zhou, N Carroll, MC Xu, B AF Zhao, Fan Heesters, Balthasar A. Chiu, Isaac Gao, Yuan Shi, Junfeng Zhou, Ning Carroll, Michael C. Xu, Bing TI L-Rhamnose-containing supramolecular nanofibrils as potential immunosuppressive materials SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID CELL PERSISTENCE; VACCINE; HYDROGEL; ADJUVANT; ANTIBODIES; MEMORY; CARBOHYDRATE; RESPONSES; DELIVERY; ANTIGEN AB An L-rhamnose-based hydrogelator self-assembles to form nanofibrils, which, in contrast to the properties of monomeric L-rhamnose, suppress the antibody response of mice to phycoerythrin (PE), a fluorescent protein antigen. As the first example of the supramolecular assemblies of a saccharide to suppress immunity, this work illustrates a new approach of immunomodulation. C1 [Zhao, Fan; Gao, Yuan; Shi, Junfeng; Zhou, Ning; Xu, Bing] Brandeis Univ, Dept Chem, Waltham, MA 02454 USA. [Heesters, Balthasar A.; Carroll, Michael C.] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA. [Heesters, Balthasar A.; Carroll, Michael C.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Heesters, Balthasar A.] Univ Med Ctr Utrecht, Dept Med Microbiol, NL-3584 CX Utrecht, Netherlands. [Chiu, Isaac] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 0211 USA. RP Carroll, MC (reprint author), Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA. EM Michael.Carroll@childrens.harvard.edu; bxu@brandeis.edu RI XU, Bing/A-7828-2008; Zhao, Fan/A-3686-2012 OI XU, Bing/0000-0002-4639-387X; Zhao, Fan/0000-0002-6103-5608 FU National Institute of Health [CA142746, AI039246, AI078897]; Kenneth Rainin Foundation; Chinese Council Scholarship FX We acknowledge the financial support provided by the National Institute of Health (CA142746, B. X.; AI039246 and AI078897, M. C. C.), innovator award from the Kenneth Rainin Foundation (B. X.), and the Chinese Council Scholarship (J. S.). We thank Brandeis EM facility for the help on EM experiment. NR 34 TC 9 Z9 9 U1 0 U2 29 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 EI 1477-0539 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2014 VL 12 IS 35 BP 6816 EP 6819 DI 10.1039/c4ob01362j PG 4 WC Chemistry, Organic SC Chemistry GA AO0TF UT WOS:000341024300008 PM 25078446 ER PT J AU Li, X Gong, YL Wu, K Liang, SH Cao, J Yang, B Hu, YZ Han, YF AF Li, Xin Gong, Yanling Wu, Kai Liang, Steven H. Cao, Ji Yang, Bo Hu, Yongzhou Han, Yifeng TI A highly sensitive and water soluble fluorescent probe for rapid detection of hydrogen sulfide in living cells SO RSC ADVANCES LA English DT Article ID BODIPY DYES; ON PROBE; FUNCTIONALIZATION; GASOTRANSMITTER; VASORELAXANT; H2S AB A highly sensitive and specific fluorescent probe has been developed for the rapid detection of H2S in living cells. This probe exhibits the unique qualities of quick response, low detection limit, excellent water solubility and good membrane permeability. Its potential for biological applications has been demonstrated by imaging H2S in living cells. C1 [Li, Xin; Gong, Yanling; Cao, Ji; Yang, Bo; Hu, Yongzhou] Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China. [Wu, Kai; Han, Yifeng] Zhejiang Sci Tech Univ, Dept Chem, Hangzhou 310018, Zhejiang, Peoples R China. [Liang, Steven H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Liang, Steven H.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Li, X (reprint author), Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China. EM lixin81@zju.edu.cn; hanyf@zstu.edu.cn FU NSFC [30901858]; Fundamental Research Funds for the Central Universities [2014FZA7016] FX This work was supported by NSFC (30901858) and the Fundamental Research Funds for the Central Universities (2014FZA7016). NR 33 TC 8 Z9 8 U1 2 U2 38 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2046-2069 J9 RSC ADV JI RSC Adv. PY 2014 VL 4 IS 68 BP 36106 EP 36109 DI 10.1039/c4ra05430j PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA AO4EH UT WOS:000341288500036 ER PT B AU Otto, MW Safren, SA Hearon, BA AF Otto, Michael W. Safren, Steven A. Hearon, Bridget A. BE Hofmann, SG DiBartolo, PM TI Mechanisms of Action in the Treatment of Social Anxiety Disorder SO SOCIAL ANXIETY: CLINICAL, DEVELOPMENTAL, AND SOCIAL PERSPECTIVES, 3RD EDITION LA English DT Article; Book Chapter ID COGNITIVE-BEHAVIORAL THERAPY; D-CYCLOSERINE ENHANCEMENT; COLLABORATIVE RESEARCH-PROGRAM; INDIVIDUAL-RESPONSE PATTERNS; RANDOMIZED CONTROLLED-TRIAL; CONTROLLED CLINICAL-TRIALS; EXPOSURE THERAPY; MAJOR DEPRESSION; DYSFUNCTIONAL ATTITUDES; SAFETY BEHAVIORS C1 [Otto, Michael W.; Hearon, Bridget A.] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA. [Safren, Steven A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. RP Otto, MW (reprint author), Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA. NR 118 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397819-6; 978-0-12-394427-6 PY 2014 BP 777 EP 800 DI 10.1016/B978-0-12-394427-6.00027-3 PG 24 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BB0YE UT WOS:000340832300028 ER PT B AU Brent, BK Fonagy, P AF Brent, Benjamin K. Fonagy, Peter BE Lysaker, PH Dimaggio, G Brune, M TI A Mentalization-Based Treatment Approach to Disturbances of Social Understanding in Schizophrenia SO SOCIAL COGNITION AND METACOGNITION IN SCHIZOPHRENIA: PSYCHOPATHOLOGY AND TREATMENT APPROACHES LA English DT Article; Book Chapter ID 1ST-DEGREE RELATIVES; MALTREATED CHILDREN; BIRTH COHORT; HIGH-RISK; MIND; PSYCHOSIS; PSYCHOTHERAPY; METAANALYSIS; DISORDERS; CHILDHOOD C1 [Brent, Benjamin K.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Brent, Benjamin K.] Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. [Brent, Benjamin K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Brent, Benjamin K.] Harvard Univ, Sch Med, Boston, MA USA. [Fonagy, Peter] UCL, London, England. RP Brent, BK (reprint author), Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 47 TC 6 Z9 6 U1 2 U2 6 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-405174-4; 978-0-12-405172-0 PY 2014 BP 245 EP 259 DI 10.1016/B978-0-12-405172-0.00015-6 PG 15 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BB0VX UT WOS:000340768200016 ER PT B AU Mansy, S Pohflepp, S AF Mansy, Sheref Pohflepp, Sascha BA Ginsberg, AD Calvert, J Schyfter, P Elfick, A Endy, D BF Ginsberg, AD Calvert, J Schyfter, P Elfick, A Endy, D TI Living Machines SO SYNTHETIC AESTHETICS: INVESTIGATING SYNTHETIC BIOLOGY'S DESIGNS ON NATURE LA English DT Article; Book Chapter C1 [Mansy, Sheref] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Mansy, Sheref] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mansy, Sheref] Univ Trento, Trento, Italy. [Pohflepp, Sascha] Art Ctr Coll Design, Los Angeles, CA USA. RP Mansy, S (reprint author), Univ Trento, Trento, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-32159-4; 978-0-262-01999-6 PY 2014 BP 247 EP 258 PG 12 WC Biotechnology & Applied Microbiology; History & Philosophy Of Science; Social Sciences, Biomedical SC Biotechnology & Applied Microbiology; History & Philosophy of Science; Biomedical Social Sciences GA BA7JM UT WOS:000337605500016 ER PT S AU Camprodon, JA Halko, MA AF Camprodon, Joan A. Halko, Mark A. BE Rotenberg, A Horvath, JC PascualLeone, A TI Combination of Transcranial Magnetic Stimulation (TMS) with Functional Magnetic Resonance Imaging SO TRANSCRANIAL MAGNETIC STIMULATION SE Neuromethods LA English DT Article; Book Chapter DE TMS; fMRI; Neuromodulation; Neuroimaging; Systems neuroscience ID POSITRON-EMISSION-TOMOGRAPHY; PRIMARY MOTOR CORTEX; CEREBRAL-BLOOD-FLOW; ANTERIOR CINGULATE CORTEX; PREFRONTAL CORTEX; BRAIN ACTIVITY; BOLD-FMRI; DEPRESSED-PATIENTS; DOPAMINE RELEASE; RANDOMIZED-TRIAL AB Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation and neuromodulation technique widely used in systems neurophysiology, cognitive neuroscience, and neuropsychiatry. Unlike other neuroimaging modalities, it is interventional and therefore able to establish causal relationships between brain activity and behavior. Despite the many advantages of independent TMS studies to demonstrate causal influence of brain areas on cognitive tasks, these studies assume TMS modulation of cortex underneath the coil but do not obtain any neurobiological measures. Multimodal approaches that combine TMS with neuroimaging, though technically challenging, are able to circumvent this problem. In this chapter, we will discuss the challenges, solutions, and applications of the combination of TMS with functional magnetic resonance imaging. C1 [Camprodon, Joan A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Halko, Mark A.] Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA 02215 USA. RP Camprodon, JA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Halko, Mark/G-8633-2016 OI Halko, Mark/0000-0002-7427-0789 NR 65 TC 1 Z9 1 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 0893-2336 BN 978-1-4939-0879-0; 978-1-4939-0878-3 J9 NEUROMETHODS JI Neuromethods PY 2014 VL 89 BP 179 EP 196 DI 10.1007/978-1-4939-0879-0_10 D2 10.1007/978-1-4939-0879-0 PG 18 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BB1OU UT WOS:000341244800012 ER PT J AU Horner-Johnson, W Dobbertin, K Andresen, EM Iezzoni, LI AF Horner-Johnson, Willi Dobbertin, Konrad Andresen, Elena M. Iezzoni, Lisa I. TI Breast and Cervical Cancer Screening Disparities Associated with Disability Severity SO WOMENS HEALTH ISSUES LA English DT Article ID FORCE RECOMMENDATION STATEMENT; UNITED-STATES; PREVENTIVE SERVICES; HEALTH-INSURANCE; MAMMOGRAPHY USE; WOMEN; RACE/ETHNICITY AB Background: Prior research has noted disparities between women with and without disabilities in receipt of timely screening for breast and cervical cancer. Some studies suggest greater disparities for women with more severe disabilities, but the research to date has yielded inconsistent findings. Our purpose was to further examine differences in receipt of breast and cervical cancer screening in relation to severity of disability. Methods: We analyzed Medical Expenditure Panel Survey annual data files from 2002 to 2008. Logistic regression analyses examined whether Pap smears and mammograms had been received within the recommended timeframe according to U. S. Preventive Services Task Force Guidelines. We compared four groups of women aged 18 to 64 years, categorized by presence and complexity of disability: 1) No limitations, 2) basic action difficulties only, 3) complex activity limitations only, and 4) both basic and complex activity limitations. Findings: Women both with and without disabilities fell short of Healthy People 2020 goals for breast and cervical cancer screening. Overall, women with disabilities were less likely to be up to date with both mammograms and Pap tests. The magnitude of disparities was greater for women with complex limitations. Disparities in Pap testing, but not mammography, remained significant when controlling for demographic, geographic, and socioeconomic factors. Conclusions: Women with more complex or severe disability were less likely to be up to date with breast and cervical cancer screenings. Targeted efforts are needed to reduce barriers to breast and cervical cancer screening for women with significant disabilities, especially those who also experience other socioecological disadvantages. Copyright (C) 2014 by the Jacobs Institute of Women's Health. Published by Elsevier Inc. C1 [Horner-Johnson, Willi; Dobbertin, Konrad; Andresen, Elena M.] Oregon Hlth & Sci Univ, Inst Dev & Disabil, Portland, OR 97239 USA. [Iezzoni, Lisa I.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Horner-Johnson, W (reprint author), Oregon Hlth & Sci Univ, Inst Dev & Disabil, 707 SW Gaines St, Portland, OR 97239 USA. EM hornerjo@ohsu.edu OI Horner-Johnson, Willi/0000-0003-3568-1400 NR 38 TC 18 Z9 18 U1 2 U2 3 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 JAN-FEB PY 2014 VL 24 IS 1 BP E147 EP E153 DI 10.1016/j.whi.2013.10.009 PG 7 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA AO1YW UT WOS:000341112500021 PM 24439941 ER PT J AU Mattocks, KM Frayne, S Phibbs, CS Yano, EM Zephyrin, L Shryock, H Haskell, S Katon, J Sullivan, JC Weinreb, L Ulbricht, C Bastian, LA AF Mattocks, Kristin M. Frayne, Susan Phibbs, Ciaran S. Yano, Elizabeth M. Zephyrin, Laurie Shryock, Holly Haskell, Sally Katon, Jodie Sullivan, J. Cherry Weinreb, Linda Ulbricht, Christine Bastian, Lori A. TI Five-year Trends in Women Veterans' Use of VA Maternity Benefits, 2008-2012 SO WOMENS HEALTH ISSUES LA English DT Article ID HEALTH-CARE; MENTAL-HEALTH; RISK-FACTORS; MEDICAID; COVERAGE; FEMALE; AFGHANISTAN; PREVALENCE; PREGNANCY; MILITARY AB Background: An increasing number of young women veterans are returning from war and military service and are seeking reproductive health care from the Veterans Health Administration (VHA). Many of these women seek maternity benefits from the VHA, and yet little is known regarding the number of women veterans utilizing VHA maternity benefits nor the characteristics of pregnant veterans using these benefits. In May 2010, VHA maternity benefits were expanded to include 7 days of infant care, which may serve to entice more women to use VHA maternity benefits. Understanding the changing trends in women veterans seeking maternity benefits will help the VHA to improve the quality of reproductive care over time. Objective: The goal of this study was to examine the trends in delivery claims among women veterans receiving VHA maternity benefits over a 5-year period and the characteristics of pregnant veterans utilizing VHA benefits. Design: We undertook a retrospective, national cohort study of pregnant veterans enrolled in VHA care with inpatient deliveries between fiscal years (FY) 2008 and 2012. Participants: We included pregnant veterans using VHA maternity benefits for delivery. Main Measures: Measures included annualized numbers and rates of inpatient deliveries and delivery-related costs, as well as cesarean section rates as a quality indicator. Key Results: During the 5-year study period, there was a significant increase in the number of deliveries to women veterans using VHA maternity benefits. The overall delivery rate increased by 44% over the study period from 12.4 to 17.8 deliveries per 1,000 women veterans. A majority of women using VHA maternity benefits were age 30 or older and had a service-connected disability. From FY 2008 to 2012, the VHA paid more than $46 million in delivery claims to community providers for deliveries to women veterans ($4,993/veteran). Conclusions: Over a 5-year period, the volume of women veterans using VHA maternity benefits increased by 44%. Given this sizeable increase, the VHA must increase its capacity to care for pregnant veterans and ensure care coordination systems are in place to address the needs of pregnant veterans with service-connected disabilities. Published by Elsevier Inc. on behalf of the Jacobs Institute of Women's Health. C1 [Mattocks, Kristin M.] VA Cent Western Massachusetts, Res & Dev, Leeds, MA USA. [Mattocks, Kristin M.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Frayne, Susan] VA Palo Alto Hlth Care Syst, VA HSR&D Ctr Excellence, Ctr Hlth Care Evaluat, Palo Alto, CA USA. [Frayne, Susan] Stanford Univ, Div Gen Med Disciplines, Palo Alto, CA 94304 USA. [Frayne, Susan] Stanford Univ, Ctr Primary Care & Outcomes Res, Palo Alto, CA 94304 USA. [Phibbs, Ciaran S.] VA Palo Alto Hlth Care Syst, VA Palo Alto Hlth Care Syst Ctr Hlth Care Evaluat, Hlth Econ Resource Ctr, Palo Alto, CA USA. [Phibbs, Ciaran S.] Stanford Univ, Sch Med, Ctr Primary Care & Outcomes Res, Dept Pediat, Stanford, CA 94305 USA. [Yano, Elizabeth M.] VA Greater Angeles HSR&D Ctr Excellence Study Hea, Sepulveda, CA USA. [Yano, Elizabeth M.] UCLA Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Zephyrin, Laurie] Dept Vet Affairs, Off Patient Care Serv, Womens Hlth Serv, New York, NY USA. [Shryock, Holly] VHA Chief Business Off, Purchased Care Program Oversight & Informat, Denver, CO USA. [Haskell, Sally] Yale Univ, Sch Med, VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. [Katon, Jodie] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Katon, Jodie] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Sullivan, J. Cherry] VA Cent Western Massachusetts Healthcare Syst, Leeds, MA USA. [Weinreb, Linda] Univ Massachusetts, Sch Med, Dept Family Med & Community Hlth, Worcester, MA USA. [Ulbricht, Christine] Univ Massachusetts, Sch Med, Worcester, MA USA. [Bastian, Lori A.] VA Connecticut, Newington, CT USA. [Bastian, Lori A.] Univ Connecticut, Div Gen Internal Med, Farmington, CT USA. RP Mattocks, KM (reprint author), VA Cent Western Massachusetts Hlth Care Syst VACW, Leeds, MA 01642 USA. EM Kristin.Mattocks@va.gov NR 34 TC 10 Z9 10 U1 1 U2 3 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 JAN-FEB PY 2014 VL 24 IS 1 BP E37 EP E42 DI 10.1016/j.whi.2013.10.002 PG 6 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA AO1YW UT WOS:000341112500007 PM 24439945 ER PT J AU Sapolsky, D Domoto-Reilly, K Dickerson, BC AF Sapolsky, Daisy Domoto-Reilly, Kimiko Dickerson, Bradford C. TI Use of the Progressive Aphasia Severity Scale (PASS) in monitoring speech and language status in PPA SO APHASIOLOGY LA English DT Article DE PPA; Aphasia; Monitoring ID DEMENTIA; DISEASE AB Background: Primary progressive aphasia (PPA) is a devastating neurodegenerative syndrome involving the gradual development of aphasia, slowly impairing the patient's ability to communicate. Pharmaceutical treatments do not currently exist and intervention often focuses on speech and language behavioural therapies, although further investigation is warranted to determine how best to harness functional benefits. Efforts to develop pharmaceutical and behavioural treatments have been hindered by a lack of standardised methods to monitor disease progression and treatment efficacy. Aims: Here, we describe our current approach to monitoring progression of PPA, including the development and applications of a novel clinical instrument for this purpose, the Progressive Aphasia Severity Scale (PASS). We also outline some of the issues related to initial evaluation and longitudinal monitoring of PPA. Methods & Procedures: In our clinical and research practice, we perform initial and follow-up assessments of PPA patients using a multifaceted approach. In addition to standardised assessment measures, we use the PASS to rate presence and severity of symptoms across distinct domains of speech, language, and functional and pragmatic aspects of communication. Ratings are made using the clinician's best judgement, integrating information from patient test performance in the office as well as a companion's description of routine daily functioning. Outcomes & Results: Monitoring symptom characteristics and severity with the PASS can assist in developing behavioural therapies, planning treatment goals, and counselling patients and families on clinical status and prognosis. The PASS also has potential to advance the implementation of PPA clinical trials. Conclusions: PPA patients display heterogeneous language profiles that change over time given the progressive nature of the disease. The monitoring of symptom progression is therefore crucial to ensure that proposed treatments are appropriate at any given stage, including speech and language therapy and potentially pharmaceutical treatments once these become available. Because of the discrepancy that can exist between a patient's daily functioning and standardised test performance, we believe a comprehensive assessment and monitoring battery must include performance-based instruments, interviews with the patient and partner, questionnaires about functioning in daily life, and measures of clinician judgement. We hope that our clinician judgement-based rating scale described here will be a valuable addition to the PPA assessment and monitoring battery. C1 [Sapolsky, Daisy; Domoto-Reilly, Kimiko; Dickerson, Bradford C.] Massachusetts Gen Hosp, Frontotemporal Dementia Unit, Boston, MA 02114 USA. [Sapolsky, Daisy; Domoto-Reilly, Kimiko; Dickerson, Bradford C.] Harvard Univ, Sch Med, Boston, MA USA. [Domoto-Reilly, Kimiko; Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sapolsky, Daisy; Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sapolsky, Daisy] Massachusetts Gen Hosp, Dept Speech & Language Pathol, Boston, MA 02114 USA. [Domoto-Reilly, Kimiko; Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Dickerson, BC (reprint author), Frontotemporal Dementia Unit, 149 13th St,Suite 2691, Charlestown, MA 02129 USA. EM bradd@nmr.mgh.harvard.edu FU NINDS [R21-NS077051] FX We appreciate the invaluable contributions of our patients and families, without which this work would not have been possible. This work was supported by NINDS [grant number R21-NS077051]. NR 18 TC 6 Z9 6 U1 2 U2 8 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0268-7038 EI 1464-5041 J9 APHASIOLOGY JI Aphasiology PY 2014 VL 28 IS 8-9 SI SI BP 993 EP 1003 DI 10.1080/02687038.2014.931563 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA AN2EE UT WOS:000340396000009 PM 25419031 ER PT J AU Lovejoy, TI Heckman, TG AF Lovejoy, Travis I. Heckman, Timothy G. TI Depression Moderates Treatment Efficacy of an HIV Secondary-Prevention Intervention for HIV-Positive Late Middle-Age and Older Adults SO BEHAVIORAL MEDICINE LA English DT Article DE depression; HIV/AIDS; moderator; motivational interviewing; sexual risk behavior ID RISKY SEXUAL-BEHAVIOR; STRESS SCALES DASS; RANDOMIZED CONTROLLED-TRIAL; CLINICAL-TRIALS; BECK DEPRESSION; PRIMARY-CARE; MEN; INFECTION; STATES; HIV/AIDS AB An estimated one-third of HIV-positive older adults continues to engage in sexual behaviors that risk HIV transmission or the acquisition of other sexually transmitted infections. A recently completed pilot randomized controlled trial of telephone-administered motivational interviewing (Tele-MI) targeting sexual risk behavior in 100 HIV-positive late middle-age and older adults found that a four-session Tele-MI intervention reduced episodes of noncondom- protected anal and vaginal intercourse. This secondary analysis examined the moderating effect of baseline depressive symptoms on intervention efficacy. When compared to one session of Tele-MI or standard of care, four sessions of Tele-MI produced greater reductions in sexual risk behavior in participants with subsyndromal depression at baseline but was no more efficacious than the other two conditions for participants with no or elevated baseline depressive symptoms. Large-scale studies that further elucidate the role of depression in sexual risk reduction interventions for HIV-positive persons are needed. C1 [Lovejoy, Travis I.] Portland VA Med Ctr, Portland, OR 97239 USA. [Lovejoy, Travis I.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Heckman, Timothy G.] Univ Georgia, Coll Publ Hlth, Athens, GA 30602 USA. RP Lovejoy, TI (reprint author), Portland VA Med Ctr, R&D 66,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM travis.lovejoy@va.gov NR 40 TC 4 Z9 4 U1 4 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0896-4289 EI 1940-4026 J9 BEHAV MED JI Behav. Med. PY 2014 VL 40 IS 3 SI SI BP 124 EP 133 DI 10.1080/08964289.2014.893982 PG 10 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA AN2YL UT WOS:000340451900006 PM 25090365 ER PT J AU Tsai, CY Hogaboom, NS Boninger, ML Koontz, AM AF Tsai, Chung-Ying Hogaboom, Nathan S. Boninger, Michael L. Koontz, Alicia M. TI The Relationship between Independent Transfer Skills and Upper Limb Kinetics in Wheelchair Users SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID SPINAL-CORD-INJURY; SITTING PIVOT TRANSFERS; UPPER EXTREMITY PAIN; LOW-LEVEL PARAPLEGIA; SHOULDER PAIN; JOINT KINEMATICS; INDIVIDUALS; PATIENT; SYSTEM; ELBOW AB Transfers are one of the most physically demanding wheelchair activities. The purpose of this study was to determine if using proper transfer skills as measured by the Transfer Assessment Instrument (TAI) is associated with reduced loading on the upper extremities. Twenty-three wheelchair users performed transfers to a level-height bench while a series of forces plates, load cells, and a motion capture system recorded the biomechanics of their natural transferring techniques. Their transfer skills were simultaneously evaluated by two study clinicians using the TAI. Logistic regression and multiple linear regression models were used to determine the relationships between TAI scores and the kinetic variables on both arms across all joints. The results showed that the TAI measured transfer skills were closely associated with the magnitude and timing of joint moments (P < .02, model R-2 values ranged from 0.27 to 0.79). Proper completion of the skills which targeted the trailing arm was associated with lower average resultant moments and rates of rise of resultant moments at the trailing shoulder and/or elbow. Some skills involving the leading side had the effect of increasing the magnitude or rate loading on the leading side. Knowledge of the kinetic outcomes associated with each skill may help users to achieve the best load-relieving effects for their upper extremities. C1 [Tsai, Chung-Ying; Hogaboom, Nathan S.; Boninger, Michael L.; Koontz, Alicia M.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. [Tsai, Chung-Ying; Hogaboom, Nathan S.; Boninger, Michael L.; Koontz, Alicia M.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. [Boninger, Michael L.; Koontz, Alicia M.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15261 USA. [Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA. RP Koontz, AM (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. EM akoontz@pitt.edu OI Hogaboom, Nathan/0000-0002-0601-5751; Boninger, Michael/0000-0001-6966-919X FU Department of Veterans Affairs [B7149I] FX This material is based upon work supported by the Department of Veterans Affairs (B7149I). NR 57 TC 2 Z9 2 U1 1 U2 3 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 984526 DI 10.1155/2014/984526 PG 12 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AN2DV UT WOS:000340394900001 ER PT J AU Guller, Y Giacino, J AF Guller, Yelena Giacino, Joseph TI Potential applications of concurrent transcranial magnetic stimulation and functional magnetic resonance imaging in acquired brain injury and disorders of consciousness SO BRAIN INJURY LA English DT Article DE Assessment; functional MRI; minimally conscious state; transcranial magnetic stimulation; vegetative state ID PERSISTENT VEGETATIVE STATE; TMS-FMRI; VISUAL-CORTEX; CORTICOSPINAL EXCITABILITY; MOTOR CORTEX; CONNECTIVITY; PARIETAL; RECOVERY; SINGLE; SCHIZOPHRENIA AB Background: Diagnostic assessment, prognosis and treatment monitoring in patients with disorders of consciousness (DoC) rest largely on behaviorally-based procedures. This approach can lead to misdiagnosis, inaccurate outcome prediction and inappropriate judgements regarding the effectiveness of treatment interventions. Concurrent transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) may provide a biological measure of conscious awareness, aid clinicians in clinical decision-making and provide a treatment alternative for DoC. Study: This paper reviews the use of TMS and fMRI in the assessment of patients with DoC and suggests potential applications for concurrent use of these procedures. C1 [Guller, Yelena; Giacino, Joseph] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Charlestown, MA 02129 USA. [Giacino, Joseph] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Giacino, Joseph] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Guller, Y (reprint author), Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, 300 First Ave, Charlestown, MA 02129 USA. EM yguller@partners.org NR 66 TC 3 Z9 3 U1 2 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PY 2014 VL 28 IS 9 SI SI BP 1190 EP 1196 DI 10.3109/02699052.2014.920527 PG 7 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AN2ZX UT WOS:000340455700008 PM 25099023 ER PT J AU Ologunde, R Maruthappu, M Shanmugarajah, K Shalhoub, J AF Ologunde, Rele Maruthappu, Mahiben Shanmugarajah, Kumaran Shalhoub, Joseph TI Surgical care in low and middle-income countries: Burden and barriers SO INTERNATIONAL JOURNAL OF SURGERY LA English DT Review DE Global surgery; Burden; Barriers ID CATARACT-SURGERY; GLOBAL HEALTH; EMERGENCY; SERVICES; ACCESS; POPULATION; CHALLENGES; CAPACITY; CHILDREN; TANZANIA AB Surgically correctable pathology accounts for a sizeable proportion of the overall global burden of disease. Over the last decade the role of surgery in the public health agenda has increased in prominence and attempts to quantify surgical capacity suggest that it is a significant public health issue, with a great disparity between high-income, and low- and middle-income countries (LMICs). Although barriers such as accessibility, availability, affordability and acceptability of surgical care hinder improvements in LMICs, evidence suggests that interventions to improve surgical care in these settings can be cost-effective. Currently, efforts to improve surgical care are mainly coordinated by academia and intuitions with strong surgical and global health interests. However, with the involvement of various international organisations, policy makers, healthcare managers and other stakeholders, a collaborative approach can be achieved in order to accelerate progress towards improved and sustainable surgical care. In this article, we discuss the current burden of global surgical disease and explore some of the barriers that may be encountered in improving surgical capacity in LMICs. We go on to consider the role that international organisations can have in improving surgical care globally. We conclude by discussing surgery as a global health priority and possible solutions to improving surgical care globally. (C) 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved. C1 [Ologunde, Rele; Shalhoub, Joseph] Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England. [Maruthappu, Mahiben] Univ Oxford, Green Templeton Coll, Oxford OX2 6HG, England. [Shanmugarajah, Kumaran] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02129 USA. RP Shalhoub, J (reprint author), Univ London Imperial Coll Sci Technol & Med, Charing Cross Hosp, Acad Sect Vasc Surg, 4th North,Fulham Palace Rd, London W6 8RF, England. EM rele.ologunde09@imperial.ac.uk; mahiben.maruthappu@gtc.ox.ac.uk; kumaran.shanmugarajah@tbrc.mgh.harvard.edu; j.shalhoub@imperial.ac.uk RI Shalhoub, Joseph/P-2171-2014 OI Shalhoub, Joseph/0000-0003-1011-7440 NR 52 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1743-9191 EI 1743-9159 J9 INT J SURG JI Int. J. Surg. PY 2014 VL 12 IS 8 BP 858 EP 863 DI 10.1016/j.ijsu.2014.07.009 PG 6 WC Surgery SC Surgery GA AN4MG UT WOS:000340561400023 PM 25019229 ER PT J AU Slatore, CG Feemster, LC Au, DH Engelberg, RA Curtis, JR Uman, J Reinke, LF AF Slatore, Christopher G. Feemster, Laura Cecere Au, David H. Engelberg, Ruth A. Curtis, J. Randall Uman, Jane Reinke, Lynn F. TI Which Patient and Clinician Characteristics Are Associated With High-Quality Communication Among Veterans With Chronic Obstructive Pulmonary Disease? SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID OF-LIFE CARE; HEALTH-CARE; PATIENTS PERCEPTIONS; COPD; SATISFACTION; PHYSICIANS; OUTCOMES; RECOMMENDATIONS; QUESTIONNAIRE; MANAGEMENT AB The authors evaluated associations of patient and clinician characteristics with high-quality communication among patients with chronic obstructive pulmonary disease. Using a cross-sectional analysis from patients with chronic obstructive pulmonary disease enrolled in a clinical trial, the authors evaluated the association of patient and clinician characteristics with patient-reported communication quality. The authors measured these associations using general estimating equations and adjusted odds ratios for best imagined communication quality. Most patient and clinician characteristics, including age, race I ethnicity, mental health attributes, and clinician specialty, were not associated with communication quality. Patient-reported clinician expertise (OR= 2.10, 95% CI [1.52, 2.88], p < .001) was associated with increased communication quality, while the patient not being married was associated with decreased quality (OR= 0.52, 95% CI [0.27, 0.99], p =.047). Only one modifiable characteristic, patient-reported clinician expertise, was associated with best imagined communication quality. This characteristic may be important to include as a potential intermediate outcome in future communication intervention studies. Predictors and outcomes of communication quality are not uniform across patient populations and settings. To maximize the effectiveness of communication interventions, it is important to have a thorough understanding of which patient, clinician, and system factors are associated with communication quality. C1 [Slatore, Christopher G.] Portland VA Med Ctr, Portland, OR 97239 USA. [Slatore, Christopher G.] Portland VA Med Ctr, Sect Pulm & Crit Care Med, Portland, OR 97239 USA. [Slatore, Christopher G.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA. [Feemster, Laura Cecere; Au, David H.; Uman, Jane; Reinke, Lynn F.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Feemster, Laura Cecere; Au, David H.; Engelberg, Ruth A.; Curtis, J. Randall] Univ Washington, Sch Med, Div Pulm & Crit Care Med, Seattle, WA USA. [Reinke, Lynn F.] Univ Washington, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. RP Slatore, CG (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,R&D 66, Portland, OR 97239 USA. EM christopher.slatore@va.gov OI Slatore, Christopher/0000-0003-0958-8122 NR 46 TC 0 Z9 0 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT 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 IS 8 BP 907 EP 921 DI 10.1080/10810730.2013.864732 PG 15 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA AN3PO UT WOS:000340500600004 PM 24558957 ER PT J AU Pecoraro, A Mimiaga, MJ O'Cleirigh, C Safren, SA Blokhina, E Verbitskaya, E Krupitsky, E Dvoriak, S Woody, G AF Pecoraro, Anna Mimiaga, Matthew J. O'Cleirigh, Conall Safren, Steven A. Blokhina, Elena Verbitskaya, Elena Krupitsky, Evgeny Dvoriak, Sergii Woody, George TI Lost-to-care and engaged-in-care HIV patients in Leningrad Oblast, Russian Federation: barriers and facilitators to medical visit retention SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE HIV; AIDS; retention; attrition; Russian Federation; positive psychology ID ANTIRETROVIRAL THERAPY; DRUG-USERS; ADHERENCE AB Sixty-nine percent of the 1.5 million Eastern Europeans and Central Asians with HIV live in the Russian Federation. Antiretroviral therapy (ART) is effective but cannot help those who leave treatment. Focus groups with patients who dropped out of ART for >= 12 months (lost-to-care, LTCs, n = 21) or continued for >= 12 months (engaged-in-care; EICs; n = 24) were conducted in St. Petersburg. Structural barriers included stigma/discrimination and problems with providers and accessing treatment. Individual barriers included employment and caring for dependents, inaccurate beliefs about ART (LTC only), side-effects, substance use (LTCs, present; EICs, past), and depression. Desire to live, social support, and spirituality were facilitators for both; EICs also identified positive thinking and experiences with ART and healthcare/professionals. Interventions to facilitate retention and adherence are discussed. C1 [Pecoraro, Anna; Woody, George] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Pecoraro, Anna; Woody, George] NIDA Clin Trials Network, Delaware Valley Node, Philadelphia, PA USA. [Mimiaga, Matthew J.; O'Cleirigh, Conall; Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Blokhina, Elena; Verbitskaya, Elena; Krupitsky, Evgeny] Pavlov State Med Univ, St Petersburg, Russia. [Dvoriak, Sergii] Ukrainian Inst Publ Hlth Policy, Kiev, Ukraine. RP Pecoraro, A (reprint author), Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. EM annp@mail.med.upenn.edu RI Verbitskaya, Elena/N-3867-2015 OI Verbitskaya, Elena/0000-0003-3770-993X FU NIDA NIH HHS [R01 DA026336, U10 DA013043]; PEPFAR NR 23 TC 2 Z9 2 U1 2 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2014 VL 26 IS 10 BP 1249 EP 1257 DI 10.1080/09540121.2014.897910 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA AM8NJ UT WOS:000340132300007 PM 24666174 ER PT J AU Levison, J Triant, V Losina, E Keefe, K Freedberg, K Regan, S AF Levison, J. Triant, V. Losina, E. Keefe, K. Freedberg, K. Regan, S. TI Development and validation of a computer-based algorithm to identify foreign-born patients with HIV infection from the electronic medical record SO APPLIED CLINICAL INFORMATICS LA English DT Article DE Foreign-born; immigrant health; HIV; classification; electronic medical record ID SOCIAL SUPPORT; LATINO; CARE; STRESS; WOMEN; MEN; SEX AB Objective: To develop and validate an efficient and accurate method to identify foreign-born patients from a large patient data registry in order to facilitate population-based health outcomes research. Methods: We developed a three-stage algorithm for classifying foreign-born status in HIV-infected patients receiving care in a large US healthcare system (January 1, 2001-March 31, 2012) (n = 9,114). In stage 1, we classified those coded as non-English language speaking as foreign-born. In stage 2, we searched free text electronic medical record (EMR) notes of remaining patients for keywords associated with place of birth and language spoken. Patients without keywords were classified as US-born. In stage 3, we retrieved and reviewed a 50-character text window around the keyword (i. e. token) for the remaining patients. To validate the algorithm, we performed a chart review and asked all HIV physicians (n = 37) to classify their patients (n = 957). We calculated algorithm sensitivity and specificity. Results: We excluded 160/957 because physicians indicated the patient was not HIV-infected (n = 54), "not my patient" (n = 103), or had unknown place of birth (n = 3), leaving 797 for analysis. In stage 1, providers agreed that 71/95 foreign language speakers were foreign-born. Most disagreements (23/24) involved patients born in Puerto Rico. In stage 2, 49/50 patients without keywords were classified as US-born by chart review. In stage 3, token review correctly classified 55/60 patients (92%), with 93% (CI: 84.4, 100%) sensitivity and 90% (CI: 74.3, 100%) specificity compared with full chart review. After application of the three-stage algorithm, 2,102/9,114 (23%) patients were classified as foreign-born. When compared against physician response, estimated sensitivity of the algorithm was 94% (CI: 90.9, 97.2%) and specificity 92% (CI: 89.7, 94.1%), with 92% correctly classified. Conclusion: A computer-based algorithm classified foreign-born status in a large HIV-infected cohort efficiently and accurately. This approach can be used to improve EMR-based outcomes research. C1 [Levison, J.; Triant, V.; Freedberg, K.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Levison, J.; Triant, V.; Losina, E.; Keefe, K.; Freedberg, K.; Regan, S.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Levison, J.; Triant, V.; Losina, E.; Keefe, K.; Freedberg, K.; Regan, S.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Levison, J.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Levison, J.; Triant, V.; Losina, E.; Keefe, K.; Freedberg, K.; Regan, S.] Harvard Univ, Sch Med, Boston, MA USA. [Losina, E.; Freedberg, K.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Losina, E.; Freedberg, K.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Losina, E.; Freedberg, K.] Harvard Univ, Ctr AIDS Res, Boston, MA USA. RP Levison, J (reprint author), Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Program HIV Epidemiol & Outcomes Res, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jlevison@partners.org FU NIAID NIH HHS [P30 AI060354]; NIMH NIH HHS [K23 MH100978] NR 23 TC 3 Z9 3 U1 0 U2 5 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 2 BP 557 EP 570 DI 10.4338/ACI-2014-02-RA-0013 PG 14 WC Medical Informatics SC Medical Informatics GA AM9MB UT WOS:000340204600008 PM 25024769 ER PT J AU Ansari, S Freire, MO Pang, EK Abdelhamid, AI Almohaimeed, M Zadeh, HH AF Ansari, Sahar Freire, Marcelo O. Pang, Eun-Kyoung Abdelhamid, Alaa I. Almohaimeed, Mohammad Zadeh, Homayoun H. TI Immobilization of Murine Anti-BMP-2 Monoclonal Antibody on Various Biomaterials for Bone Tissue Engineering SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID MESENCHYMAL STEM-CELLS; MEDIATED OSSEOUS REGENERATION; GROWTH-FACTOR DELIVERY; MORPHOGENETIC PROTEIN-2; IN-VITRO; SIGNALING PATHWAY; TGF-BETA/BMP; RHBMP-2; DIFFERENTIATION; MICROSPHERES AB Biomaterials are widely used as scaffolds for tissue engineering. We have developed a strategy for bone tissue engineering that entails application of immobilized anti-BMP-2 monoclonal antibodies (mAbs) to capture endogenous BMPs in vivo and promote antibody-mediated osseous regeneration (AMOR). The purpose of the current study was to compare the efficacy of immobilization of a specific murine anti-BMP-2 mAb on three different types of biomaterials and to evaluate their suitability as scaffolds for AMOR. Anti-BMP-2 mAb or isotype control mAb was immobilized on titanium (Ti) microbeads, alginate hydrogel, and ACS. The treated biomaterials were surgically implanted in rat critical-sized calvarial defects. After 8 weeks, de novo bone formation was assessed using micro-CT and histomorphometric analyses. Results showed de novo bone regeneration with all three scaffolds with immobilized anti-BMP-2 mAb, but not isotype control mAb. Ti microbeads showed the highest volume of bone regeneration, followed by ACS. Alginate showed the lowest volume of bone. Localization of BMP-2, -4, and -7 antigens was detected on all 3 scaffolds with immobilized anti-BMP-2mAb implanted in calvarial defects. Altogether, these data suggested a potential mechanism for bone regeneration through entrapment of endogenous BMP-2, -4, and -7 proteins leading to bone formation using different types of scaffolds via AMOR. C1 [Ansari, Sahar; Zadeh, Homayoun H.] Univ So Calif, Herman Ostrow Sch Dent, Lab Immune Regulat & Tissue Engn, Los Angeles, CA 90045 USA. [Freire, Marcelo O.] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA USA. [Freire, Marcelo O.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Pang, Eun-Kyoung] Ewha Womans Univ, Grad Sch Med, Dept Periodontol, Seoul, South Korea. [Abdelhamid, Alaa I.; Almohaimeed, Mohammad] Qassim Univ, Qassim Coll Dent, Dent Res Ctr, Buraydah, Saudi Arabia. [Abdelhamid, Alaa I.; Almohaimeed, Mohammad] Qassim Univ, Qassim Coll Dent, Tissue Engn Unit TERU, Buraydah, Saudi Arabia. [Zadeh, Homayoun H.] Univ So Calif, Ostrow Sch Dent, Div Periodontol Diagnost Sci & Dent Hyg, Lab Immune Regulat & Tissue Engn LITE, Los Angeles, CA 90089 USA. RP Zadeh, HH (reprint author), Univ So Calif, Herman Ostrow Sch Dent, Lab Immune Regulat & Tissue Engn, Los Angeles, CA 90045 USA. EM zadeh@usc.edu OI Freire, Marcelo/0000-0003-4906-7698 FU NIDCR [T90DE021982]; Long Term Comprehensive National Plan for Science, Technology and Innovation Grant from Saudi Arabia [10BIO1228-09] FX The first author (Sahar Ansari) was supported by a NIDCR training Grant (T90DE021982). This work was partially supported by The Long Term Comprehensive National Plan for Science, Technology and Innovation Grant from Saudi Arabia (10BIO1228-09) to the fourth author (Alaa I. Abdelhamid). NR 34 TC 2 Z9 3 U1 2 U2 6 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 940860 DI 10.1155/2014/940860 PG 10 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AM8WL UT WOS:000340159400001 ER PT S AU Tena, A Sachs, DH AF Tena, Aseda Sachs, David H. BE CasaroliMarano, RP Zarbin, MA TI Stem Cells: Immunology and Immunomodulation SO CELL-BASED THERAPY FOR RETINAL DEGENERATIVE DISEASE SE Developments in Ophthalmology LA English DT Article; Book Chapter ID MARROW STROMAL CELLS; REGULATORY T-CELLS; IMMUNE PRIVILEGE; MACULAR DEGENERATION; MIXED CHIMERISM; BONE-MARROW; FAS LIGAND; IN-VIVO; HLA-G; RENAL-TRANSPLANTATION AB Multipotent progenitor cells have the ability to differentiate in vitro into tissue-specific cells under the proper cellular signaling conditions. Because of this intrinsic property, pluripotent derived stem cells from embryonic tissues, induced from genetic reprogramming of somatic cells or from mesenchymal cells, have become the focus of many regenerative medicine studies directed toward application to clinical settings. Generation of retinal pigment epithelium derived from patient-specific, induced pluripotent stem cells may create the ability to recapitulate the disease state and screen new therapeutics, improving upon the limited treatment strategies currently available for afflicted patients. However, the method of delivery, cell culture differentiation, and immunological rejection are some of the limitations that continue to influence ongoing attempts for clinical applications. Understanding stem cell properties and the immune responses these cells elicit in vitro and in vivo will be of importance for designing successful protocols to overcome these immunological limitations. This chapter examines the immunological and immunomodulatory properties of multipotent stem cells in an attempt to provide insights for successful cellular transplantation. (C) 2014 S. Karger AG, Basel C1 [Tena, Aseda; Sachs, David H.] Harvard Univ, Transplantat Biol Res Ctr, Sch Med, Boston, MA 02129 USA. [Tena, Aseda; Sachs, David H.] Massachusetts Gen Hosp, Boston, MA 02129 USA. RP Sachs, DH (reprint author), Harvard Univ, Transplantat Biol Res Ctr, Sch Med, 149 13th St,Suite 9019, Boston, MA 02129 USA. EM Aseda.Tena@tbrc.mgh.harvard.edu; david.sachs@tbrc.mgh.harvard.edu NR 76 TC 6 Z9 7 U1 0 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0250-3751 BN 978-3-318-02585-9; 978-3-318-02584-2 J9 DEV OPHTHALMOL JI Dev. Ophthalmol. PY 2014 VL 53 BP 122 EP 132 DI 10.1159/000357360 PG 11 WC Cell & Tissue Engineering; Ophthalmology SC Cell Biology; Ophthalmology GA BB0DA UT WOS:000340105000010 PM 24732766 ER PT S AU Faverio, P Restrepo, MI AF Faverio, Paola Restrepo, Marcos I. BE Chalmers, JD Pletz, MW Aliberti, S Welte, T TI Non-antibiotic therapies for CAP SO COMMUNITY-ACQUIRED PNEUMONIA SE European Respiratory Monograph LA English DT Article; Book Chapter ID COMMUNITY-ACQUIRED PNEUMONIA; CONVERTING-ENZYME-INHIBITORS; RANDOMIZED CONTROLLED-TRIAL; FACTOR PATHWAY INHIBITOR; PSEUDOMONAS-AERUGINOSA PNEUMONIA; PLACEBO-CONTROLLED TRIAL; NITRIC-OXIDE INHALATION; II RECEPTOR BLOCKERS; INTENSIVE-CARE-UNIT; LUNG FLUID BALANCE AB Several novel non-antibiotic therapies have been used in patients with pneumonia. Among many alternatives, anti-inflammatory and immunomodulatory agents such as corticosteroids, statins, nonsteroid anti-inflammatory medications, immunoglobulins and anticoagulants have been tested. Other agents, such as angiotensin-converting enzyme inhibitors and mucolytics, showed a potential beneficial effect on airways protection mechanisms and secretion clearance. The therapeutic effect of nonpharmacological strategies (i.e. chest physiotherapy) has also been considered. However, other than use of corticosteroids in certain populations, there is still a need for further research before these medications are recommended for clinical use. This chapter discusses the evidence regarding novel non-antibiotic therapies and the association with clinical outcomes in patients with pneumonia. C1 [Faverio, Paola] Univ Milano Bicocca, Dept Hlth Sci, Clin Pneumol, AO San Gerardo, Monza, Italy. [Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Restrepo, MI (reprint author), South Texas Vet Hlth Care Syst ALMD, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM restrepom@uthscsa.edu NR 92 TC 1 Z9 1 U1 0 U2 0 PU EUROPEAN RESPIRATORY SOCIETY PI SHEFFIELD PA 442 GLOSSOP ROAD, SHEFFIELD, S10 2PX, ENGLAND SN 2075-6674 BN 978-1-84984-049-1; 978-1-84984-048-4 J9 EUR RESPIR MONOGR PY 2014 IS 63 BP 219 EP 233 DI 10.1183/1025448x.10004513 D2 10.1183/1025448x.erm6314 PG 15 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA BA9YL UT WOS:000339965900018 ER PT J AU Hirsch, J Chalkley, RJ Bentley, T Burlingame, AL Frank, JA AF Hirsch, Jan Chalkley, Robert J. Bentley, Trevor Burlingame, Alma L. Frank, James A. TI Double impact of cigarette smoke and mechanical ventilation on the alveolar epithelial type II cell SO CRITICAL CARE LA English DT Article ID ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; QUADRUPOLE COLLISION CELL; FLIGHT MASS-SPECTROMETER; RISK-FACTORS; BRONCHOALVEOLAR LAVAGE; COMPREHENSIVE ANALYSIS; MEMBRANE-PROTEINS; OXIDATIVE STRESS; TIDAL VOLUMES AB Introduction: Ventilator-induced lung injury (VILI) impacts clinical outcomes in acute respiratory distress syndrome (ARDS), which is characterized by neutrophil-mediated inflammation and loss of alveolar barrier function. Recent epidemiological studies suggest that smoking may be a risk factor for the development of ARDS. Because alveolar type II cells are central to maintaining the alveolar epithelial barrier during oxidative stress, mediated in part by neutrophilic inflammation and mechanical ventilation, we hypothesized that exposure to cigarette smoke and mechanical strain have interactive effects leading to the activation of and damage to alveolar type II cells. Methods: To determine if cigarette smoke increases susceptibility to VILI in vivo, a clinically relevant rat model was established. Rats were exposed to three research cigarettes per day for two weeks. After this period, some rats were mechanically ventilated for 4 hours. Bronchoalveolar lavage (BAL) and differential cell count was done and alveolar type II cells were isolated. Proteomic analysis was performed on the isolated alveolar type II cells to discover alterations in cellular pathways at the protein level that might contribute to injury. Effects on levels of proteins in pathways associated with innate immunity, oxidative stress and apoptosis were evaluated in alveolar type II cell lysates by enzyme-linked immunosorbent assay. Statistical comparisons were performed by t-tests, and the results were corrected for multiple comparisons using the false discovery rate. Results: Tobacco smoke exposure increased airspace neutrophil influx in response to mechanical ventilation. The combined exposure to cigarette smoke and mechanical ventilation significantly increased BAL neutrophil count and protein content. Neutrophils were significantly higher after smoke exposure and ventilation than after ventilation alone. DNA fragments were significantly elevated in alveolar type II cells. Smoke exposure did not significantly alter other protein-level markers of cell activation, including Toll-like receptor 4; caspases 3, 8 and 9; and heat shock protein 70. Conclusions: Cigarette smoke exposure may impact ventilator-associated alveolar epithelial injury by augmenting neutrophil influx. We found that cigarette smoke had less effect on other pathways previously associated with VILI, including innate immunity, oxidative stress and apoptosis. C1 [Hirsch, Jan; Chalkley, Robert J.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Hirsch, Jan; Chalkley, Robert J.] San Francisco VA Med Ctr, Anesthesia Serv, San Francisco, CA 94121 USA. [Bentley, Trevor; Burlingame, Alma L.; Frank, James A.] Univ Calif San Francisco, Dept Pharmaceut Chem, Mass Spectrometry Facil, San Francisco, CA 94158 USA. [Bentley, Trevor; Burlingame, Alma L.; Frank, James A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Bentley, Trevor; Burlingame, Alma L.; Frank, James A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Bentley, Trevor; Burlingame, Alma L.; Frank, James A.] San Francisco VA Med Ctr, Med Serv, Div Pulm, San Francisco, CA 94121 USA. RP Hirsch, J (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. EM jan.hirsch@ucsf.edu FU National Institutes of Health [8P41GM103481, HL088440]; intramural Research Evaluation and Allocation Committee grant from the University of California, San Francisco; Department of Anesthesia and Perioperative Care at the University of California, San Francisco; Northern California Institute for Research and Education FX This study was supported in part by grants from the National Institutes of Health (8P41GM103481 to ALB and HL088440 to JAF), an intramural Research Evaluation and Allocation Committee grant from the University of California, San Francisco (to JH), and startup funds from the Department of Anesthesia and Perioperative Care at the University of California, San Francisco, and the Northern California Institute for Research and Education (to JH). No private funding was used. This national and university grant funding provided resources for the design, collection, analysis and interpretation of data as well as salary support. The writing of the manuscript and the decision to submit it for publication were carried out by the authors without the participation or influence of, or restrictions by, any of the funding sources. NR 54 TC 5 Z9 5 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2014 VL 18 IS 2 AR R50 DI 10.1186/cc13795 PG 12 WC Critical Care Medicine SC General & Internal Medicine GA AM1SA UT WOS:000339627400068 PM 24666941 ER PT J AU Kida, K Ichinose, F AF Kida, Kotaro Ichinose, Fumito TI Preventing ischemic brain injury after sudden cardiac arrest using NO inhalation SO CRITICAL CARE LA English DT Review ID INHALED NITRIC-OXIDE; AMERICAN-HEART-ASSOCIATION; EMERGENCY CARDIOVASCULAR CARE; DECREASES INFARCTION SIZE; CARDIOPULMONARY-RESUSCITATION; MYOCARDIAL-ISCHEMIA; REPERFUSION INJURY; SURVIVAL; MICE; HYPOTHERMIA C1 [Kida, Kotaro; Ichinose, Fumito] Massachusetts Gen Hosp, Dept Anesthesia & Intens Care, Charlestown, MA 02129 USA. RP Ichinose, F (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Intens Care, Charlestown, MA 02129 USA. EM fichinose@partners.org FU Ikaria, Inc FX Dr Ichinose has received a sponsored research agreement from Ikaria, Inc that makets inhaled NO (INOMAX) in the US. NR 50 TC 4 Z9 4 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2014 VL 18 IS 2 AR 212 DI 10.1186/cc13779 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA AM1SA UT WOS:000339627400028 PM 25029464 ER PT J AU Villar, J Muros, M Cabrera-Benitez, NE Valladares, F Lopez-Hernandez, M Flores, C Martin-Barrasa, JL Blanco, J Liu, MY Kacmarek, RM AF Villar, Jesus Muros, Mercedes Cabrera-Benitez, Nuria E. Valladares, Francisco Lopez-Hernandez, Milagros Flores, Carlos Martin-Barrasa, Jose L. Blanco, Jesus Liu, Mingyao Kacmarek, Robert M. TI Soluble platelet-endothelial cell adhesion molecule-1, a biomarker of ventilator-induced lung injury SO CRITICAL CARE LA English DT Article ID END-EXPIRATORY PRESSURE; RESPIRATORY-DISTRESS-SYNDROME; MECHANICAL VENTILATION; PULMONARY CAPILLARIES; PECAM-1; SEPSIS; MICROPARTICLES; INFLAMMATION; DYSFUNCTION; EXPRESSION AB Introduction: Endothelial cell injury is an important component of acute lung injury. Platelet-endothelial cell adhesion molecule-1 (PECAM1) is a transmembrane protein that connects endothelial cells to one another and can be detected as a soluble, truncated protein (sPECAM1) in serum. We hypothesized that injurious mechanical ventilation (MV) leads to shedding of PECAM1 from lung endothelial cells resulting in increasing sPECAM1 levels in the systemic circulation. Methods: We studied 36 Sprague-Dawley rats in two prospective, randomized, controlled studies (healthy and septic) using established animal models of ventilator-induced lung injury. Animals (n = 6 in each group) were randomized to spontaneous breathing or two MV strategies: low tidal volume (V-T) (6 ml/kg) and high-V-T (20 ml/kg) on 2 cmH(2)O of positive end-expiratory pressure (PEEP). In low-V-T septic animals, 10 cmH(2)O of PEEP was applied. We performed pulmonary histological and physiological evaluation and measured lung PECAM1 protein content and serum sPECAM1 levels after four hours ventilation period. Results: High-V-T MV caused severe lung injury in healthy and septic animals, and decreased lung PECAM1 protein content (P < 0.001). Animals on high-V-T had a four-to six-fold increase of mean sPECAM1 serum levels than the unventilated counterpart (35.4 +/- 10.4 versus 5.6 +/- 1.7 ng/ml in healthy rats; 156.8 +/- 47.6 versus 35.6 +/- 12.6 ng/ml in septic rats) (P < 0.0001). Low-V-T MV prevented these changes. Levels of sPECAM1 in healthy animals on high-V-T MV paralleled the sPECAM1 levels of non-ventilated septic animals. Conclusions: Our findings suggest that circulating sPECAM1 may represent a promising biomarker for the detection and monitoring of ventilator-induced lung injury. C1 [Villar, Jesus; Muros, Mercedes; Cabrera-Benitez, Nuria E.; Valladares, Francisco; Flores, Carlos; Martin-Barrasa, Jose L.; Blanco, Jesus] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, Jesus; Cabrera-Benitez, Nuria E.; Martin-Barrasa, Jose L.] Hosp Univ Dr Negrin, Res Unit, Multidisciplinary Organ Dysfunct Evaluat Res Net, Las Palmas Gran Canaria, Spain. [Villar, Jesus] St Michaels Hosp, Keenan Res Ctr Biomed Sci, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada. [Muros, Mercedes] Hosp Univ NS de Candelaria, Dept Clin Biochem, Tenerife, Spain. [Valladares, Francisco; Lopez-Hernandez, Milagros] Univ La Laguna, Dept Anat Pathol & Histol, Tenerife, Spain. [Flores, Carlos] Hosp Univ NS de Candelaria, Res Unit, Santa Cruz De Tenerife, Spain. [Blanco, Jesus] Hosp Univ Rio Hortega, Intens Care Unit, Valladolid, Spain. [Liu, Mingyao] Univ Toronto, Fac Med, Inst Med Sci, Toronto, ON, Canada. [Liu, Mingyao] Univ Hlth Network, Toronto Gen Res Inst, Resp & Crit Care Res Grp, Toronto, ON, Canada. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Kacmarek, Robert M.] Harvard Univ, Dept Anesthesiol, Boston, MA 02115 USA. RP Villar, J (reprint author), Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. EM jesus.villar54@gmail.com FU Instituto de Salud Carlos III, Madrid, Spain [PI10/0393, CB06/06/1088] FX Supported in part by grants (PI10/0393, CB06/06/1088) from Instituto de Salud Carlos III, Madrid, Spain. NR 45 TC 2 Z9 2 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2014 VL 18 IS 2 AR R41 DI 10.1186/cc13754 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA AM1SA UT WOS:000339627400059 PM 24588994 ER PT J AU Closson, EF Sivasubramanian, M Mayer, KH Srivastava, A Safren, SA Anand, VR Gangakhedkar, R Mimiaga, MJ AF Closson, Elizabeth F. Sivasubramanian, Murugesan Mayer, Kenneth H. Srivastava, Ankur Safren, Steven A. Anand, Vivek Raj Gangakhedkar, Raman Mimiaga, Matthew J. TI The other side of the bridge: exploring the sexual relationships of men who have sex with men and their female partners in Mumbai, India SO CULTURE HEALTH & SEXUALITY LA English DT Article DE India; HIV/AIDS; bisexual men; women ID HIV PREVENTION; IDENTIFIED MEN; CONDOM USE; CHENNAI; RISK; WORKERS; INTERVENTION; PREVALENCE; INFECTION; CONTEXTS AB Behaviourally bisexual men have been identified as a 'bridge' population of HIV transmission to heterosexual women in India. Little is known about the sexual relationships that these men have with their female sex partners. The primary objective of this study was to explore the sexual practices and relationship dynamics between married and unmarried behaviourally bisexual men and their female sex partners in Mumbai, India. In 2009, semi-structured qualitative interviews were conducted with 32 men who reported sex with men and women. Participants discussed a variety of sexual practices and arrangements with female sex partners. Irrespective of marital status and sexual identity, many said that they had satisfying sexual experiences and feelings of affection for female sex partners. However, sexual incompatibility between married partners was also reported. Explanations of bisexual concurrency were discussed in terms of both sexual satisfaction and sexual preference. Self-perceived HIV risk related to same-sex sexual behaviour motivated many men to use condoms with female partners. Expectations of unprotected marital sex and perceptions of partner risk were barriers to condom use. HIV-prevention programmes for this population may benefit from tailored risk-reduction counselling that attends to the variations of these sexual and social relationship dynamics. C1 [Closson, Elizabeth F.; Mayer, Kenneth H.; Safren, Steven A.; Mimiaga, Matthew J.] Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. [Sivasubramanian, Murugesan; Srivastava, Ankur; Anand, Vivek Raj] Humsafar Trust, Bombay, Maharashtra, India. [Mayer, Kenneth H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Mayer, Kenneth H.] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Gangakhedkar, Raman] Natl AIDS Res Inst, Pune, Maharashtra, India. [Safren, Steven A.; Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Mimiaga, MJ (reprint author), Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. EM mmimiaga@partners.org FU NIMH NIH HHS [R21 MH085319, #1 R21 MH085319-01] NR 36 TC 5 Z9 5 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1369-1058 EI 1464-5351 J9 CULT HEALTH SEX JI Cult. Health Sex PY 2014 VL 16 IS 7 BP 780 EP 791 DI 10.1080/13691058.2014.911960 PG 12 WC Family Studies; Social Sciences, Biomedical SC Family Studies; Biomedical Social Sciences GA AM8CY UT WOS:000340099000005 PM 24815724 ER PT S AU Tambouret, R AF Tambouret, Rosemary BE Nayar, R TI Female Genital Tract SO CYTOPATHOLOGY IN ONCOLOGY SE Cancer Treatment and Research LA English DT Article; Book Chapter ID HIGH-RISK HPV; PERITONEAL WASHING CYTOLOGY; HUMAN-PAPILLOMAVIRUS DNA; INVASIVE CERVICAL-CANCER; FINE-NEEDLE-ASPIRATION; HYBRID CAPTURE 2; ASC-US CYTOLOGY; SQUAMOUS INTRAEPITHELIAL LESIONS; ADENOCARCINOMA IN-SITU; LIQUID-BASED CYTOLOGY C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Tambouret, R (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 105-55 Fruit St, Boston, MA 02114 USA. EM RTAMBOURET@PARTNERS.ORG NR 137 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0927-3042 BN 978-3-642-38850-7; 978-3-642-38849-1 J9 CANCER TREAT RES JI Canc. Treat. Res. PY 2014 VL 160 BP 241 EP 272 DI 10.1007/978-3-642-38850-7_10 D2 10.1007/978-3-642-38850-7 PG 32 WC Oncology SC Oncology GA BA7AM UT WOS:000337346100011 PM 24092373 ER EF