FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Menendez, ME Bot, AGJ Hageman, MGJS Neuhaus, V Mudgal, CS Ring, D AF Menendez, Mariano E. Bot, Arjan G. J. Hageman, Michiel G. J. S. Neuhaus, Valentin Mudgal, Chaitanya S. Ring, David TI Computerized Adaptive Testing of Psychological Factors: Relation to Upper-Extremity Disability SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Editorial Material C1 [Menendez, Mariano E.; Bot, Arjan G. J.; Hageman, Michiel G. J. S.; Neuhaus, Valentin; Mudgal, Chaitanya S.; Ring, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Menendez, ME (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 EI 1535-1386 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD OCT 16 PY 2013 VL 95A IS 20 BP 1844 EP 1844 PG 1 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 244DQ UT WOS:000326367700005 ER PT J AU Devor, A Bandettini, PA Boas, DA Bower, JM Buxton, RB Cohen, LB Dale, AM Einevoll, GT Fox, PT Franceschini, MA Friston, KJ Fujimoto, JG Geyer, MA Greenberg, JH Halgren, E Hamalainen, MS Helmchen, F Hyman, BT Jasanoff, A Jernigan, TL Judd, LL Kim, SG Kleinfeld, D Kopell, NJ Kutas, M Kwong, KK Larkum, ME Lo, EH Magistretti, PJ Mandeville, JB Masliah, E Mitra, PP Mobley, WC Moskowitz, MA Nimmerjahn, A Reynolds, JH Rosen, BR Salzberg, BM Schaffer, CB Silva, GA So, PTC Spitzer, NC Toote, RB Van Essen, DC Vanduffel, W Vinogradov, SA Wald, LL Wang, LV Weber, B Yodh, AG AF Devor, Anna Bandettini, Peter A. Boas, David A. Bower, James M. Buxton, Richard B. Cohen, Lawrence B. Dale, Anders M. Einevoll, Gaute T. Fox, Peter T. Franceschini, Maria Angela Friston, Karl J. Fujimoto, James G. Geyer, Mark A. Greenberg, Joel H. Halgren, Eric Haemaelaeinen, Math S. Helmchen, Fritjof Hyman, Bradley T. Jasanoff, Alan Jernigan, Terry L. Judd, Lewis L. Kim, Seong-Gi Kleinfeld, David Kopell, Nancy J. Kutas, Marta Kwong, Kenneth K. Larkum, Matthew E. Lo, Eng H. Magistretti, Pierre J. Mandeville, Joseph B. Masliah, Eliezer Mitra, Partha P. Mobley, William C. Moskowitz, Michael A. Nimmerjahn, Axel Reynolds, John H. Rosen, Bruce R. Salzberg, Brian M. Schaffer, Chris B. Silva, Gabriel A. So, Peter T. C. Spitzer, Nicholas C. Toote, Roger B. Van Essen, David C. Vanduffel, Wim Vinogradov, Sergei A. Wald, Lawrence L. Wang, Lihong V. Weber, Bruno Yodh, Arjun G. TI The Challenge of Connecting the Dots in the BRAIN SO NEURON LA English DT Editorial Material AB The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative has focused scientific attention on the necessary tools to understand the human brain and mind. Here, we outline our collective vision for what we can achieve within a decade with properly targeted efforts and discuss likely technological deliverables and neuroscience progress. C1 [Devor, Anna; Dale, Anders M.; Halgren, Eric; Kutas, Marta; Masliah, Eliezer; Mobley, William C.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Devor, Anna; Buxton, Richard B.; Dale, Anders M.; Halgren, Eric; Jernigan, Terry L.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Devor, Anna; Boas, David A.; Franceschini, Maria Angela; Haemaelaeinen, Math S.; Kwong, Kenneth K.; Mandeville, Joseph B.; Rosen, Bruce R.; Toote, Roger B.; Vanduffel, Wim; Wald, Lawrence L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Bandettini, Peter A.] NIH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Bandettini, Peter A.] NIMH, Funct MRI Facil, NIH, Bethesda, MD 20892 USA. [Bower, James M.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Cohen, Lawrence B.] Korea Inst Sci & Technol, Ctr Funct Connect, Seoul 139791, South Korea. [Cohen, Lawrence B.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. [Einevoll, Gaute T.] Norwegian Univ Life Sci, Dept Math Sci & Technol, N-1432 As, Norway. [Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Fox, Peter T.] Audie L Murphy South Texas Vet Adm Med Ctr, San Antonio, TX 78229 USA. [Friston, Karl J.] Wellcome Trust Ctr Neuroimaging, London WC1N 3BG, England. [Fujimoto, James G.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Fujimoto, James G.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Geyer, Mark A.; Jernigan, Terry L.; Judd, Lewis L.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Greenberg, Joel H.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Helmchen, Fritjof] Univ Zurich, Brain Res Inst, CH-8057 Zurich, Switzerland. [Helmchen, Fritjof; Weber, Bruno] Univ Zurich, Neurosci Ctr Zurich, CH-8057 Zurich, Switzerland. [Helmchen, Fritjof; Weber, Bruno] ETH, CH-8092 Zurich, Switzerland. [Hyman, Bradley T.] Harvard Univ, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol,Alzheimers Dis Res Lab,Med Sch, Charlestown, MA 02129 USA. [Jasanoff, Alan] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Jasanoff, Alan] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Jasanoff, Alan] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Jasanoff, Alan] MIT, Dept Nucl Sci & Engn, Cambridge, MA 02139 USA. [Jernigan, Terry L.] Univ Calif San Diego, Ctr Human Dev, La Jolla, CA 92093 USA. [Jernigan, Terry L.; Kutas, Marta] Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA. [Kim, Seong-Gi] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15203 USA. [Kim, Seong-Gi] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA 15203 USA. [Kleinfeld, David] Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA. [Kleinfeld, David] Univ Calif San Diego, Neurobiol Sect, La Jolla, CA 92093 USA. [Kopell, Nancy J.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Kutas, Marta] Univ Calif San Diego, Ctr Res Language, La Jolla, CA 92093 USA. [Larkum, Matthew E.] Charite, Neurosci Res Ctr NWFZ, D-10117 Berlin, Germany. [Lo, Eng H.; Moskowitz, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Neurosci Ctr,Med Sch, Boston, MA 02129 USA. [Lo, Eng H.; Moskowitz, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Neurosci Ctr,Med Sch, Boston, MA 02129 USA. [Magistretti, Pierre J.] Ecole Polytech Fed Lausanne, Brain Mind Inst, Lab Neuroenerget & Cellular Dynam, CH-1015 Lausanne, Switzerland. [Magistretti, Pierre J.] Univ Lausanne, CH-1015 Lausanne, Switzerland. [Mitra, Partha P.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Nimmerjahn, Axel] Salk Inst Biol Studies, Waitt Adv Biophoton Ctr, La Jolla, CA 92037 USA. [Reynolds, John H.] Salk Inst Biol Studies, Syst Neurobiol Labs, La Jolla, CA 92037 USA. [Salzberg, Brian M.] Univ Penn, Perelman Sch Med, Dept Neurosci, Philadelphia, PA 19104 USA. [Salzberg, Brian M.] Univ Penn, Perelman Sch Med, Dept Physiol, Philadelphia, PA 19104 USA. [Schaffer, Chris B.] Cornell Univ, Dept Biomed Engn, Ithaca, NY 14850 USA. [Silva, Gabriel A.] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Silva, Gabriel A.] Univ Calif San Diego, Dept Ophthalmol, La Jolla, CA 92093 USA. [So, Peter T. C.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [So, Peter T. C.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Spitzer, Nicholas C.] Univ Calif San Diego, Div Biol Sci, Kavli Inst Brain & Mind, Neurobiol Sect, La Jolla, CA 92093 USA. [Toote, Roger B.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Van Essen, David C.] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. [Vanduffel, Wim] Katholieke Univ Leuven, Sch Med, Lab Neuro & Psychofysiol, B-3000 Louvain, Belgium. [Vinogradov, Sergei A.] Univ Penn, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. [Wang, Lihong V.] Washington Univ, Dept Biomed Engn, St Louis, MO 63130 USA. [Weber, Bruno] Univ Zurich, Inst Pharmacol & Toxicol, CH-8057 Zurich, Switzerland. [Yodh, Arjun G.] Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA. RP Devor, A (reprint author), Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. EM adevor@ucsd.edu RI Hamalainen, Matti/C-8507-2013; Schaffer, Chris/A-7409-2008; Friston, Karl/D-9230-2011; Fox, Peter/B-4725-2010; Weber, Bruno/E-4400-2013; Wald, Lawrence/D-4151-2009 OI Schaffer, Chris/0000-0002-7800-9596; Friston, Karl/0000-0001-7984-8909; Fox, Peter/0000-0002-0465-2028; FU NEI NIH HHS [R01 EY022096]; NIBIB NIH HHS [P41 EB015871, R01 EB000790, R01 EB003832]; NICHD NIH HHS [R01 HD022614]; NIDA NIH HHS [R01 DA029706]; NIH HHS [DP1 OD006831]; NINDS NIH HHS [DP1 NS082097, R01 NS040966, R01 NS057198, R01 NS058668]; Wellcome Trust [091593, 088130] NR 1 TC 30 Z9 30 U1 4 U2 53 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD OCT 16 PY 2013 VL 80 IS 2 BP 270 EP 274 DI 10.1016/j.neuron.2013.09.008 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 241VI UT WOS:000326196400009 PM 24139032 ER PT J AU Suh, J Choi, SH Romano, DM Gannon, MA Lesinski, AN Kim, DY Tanzi, RE AF Suh, Jaehong Choi, Se Hoon Romano, Donna M. Gannon, Moira A. Lesinski, Andrea N. Kim, Doo Yeon Tanzi, Rudolph E. TI ADAM10 Missense Mutations Potentiate beta-Amyloid Accumulation by Impairing Prodomain Chaperone Function SO NEURON LA English DT Article ID ALPHA-SECRETASE ACTIVITY; PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; PROTEOLYTIC ACTIVITY; IN-VIVO; DISINTEGRIN; DOMAIN; BRAIN; APP; PROLIFERATION AB The generation of A beta, the main component of senile plaques in Alzheimer's disease (AD), is precluded by alpha-secretase cleavage within the A beta domain of the amyloid precursor protein (APP). We identified two rare mutations (Q170H and R181G) in the prodomain of the metalloprotease, ADAM10, that cosegregate with late-onset AD (LOAD). Here, we addressed the pathogenicity of these mutations in transgenic mice expressing human ADAM10 in brain. In Tg2576 AD mice, both mutations attenuated alpha-secretase activity of ADAM10 and shifted APP processing toward beta-secretase-mediated cleavage, while enhancing A beta plaque load and reactive gliosis. We also demonstrated ADAM10 expression potentiates adult hippocampal neurogenesis, which is reduced by the LOAD mutations. Mechanistically, both LOAD mutations impaired the molecular chaperone activity of ADAM10 prodomain. Collectively, these findings suggest that diminished alpha-secretase activity, owing to LOAD ADAM10 prodomain mutations, leads to AD-related pathology, strongly supporting ADAM10 as a promising therapeutic target for this devastating disease. C1 [Suh, Jaehong; Choi, Se Hoon; Romano, Donna M.; Gannon, Moira A.; Lesinski, Andrea N.; Kim, Doo Yeon; Tanzi, Rudolph E.] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit, Boston, MA 02129 USA. [Suh, Jaehong; Choi, Se Hoon; Romano, Donna M.; Gannon, Moira A.; Lesinski, Andrea N.; Kim, Doo Yeon; Tanzi, Rudolph E.] Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit, Boston, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu FU Cure Alzheimer's Fund; NIA, NIMH; American Health Assistance Foundation FX We thank Dr. Lin Wu for her scientific expertise and technical assistance in generating ADAM10 transgenic mice. We also thank Dr. Jorg Bartsch for providing ADAM10 prodomain antibody; Dr. Sam Sisodia for providing MoPrP.Xhol plasmid; Dr. Matthew Frosch for providing Tg2576 mice; Dr. Basavaraj Hooli and Dr. Can Zhang for helpful discussions; and William Wisdom for mouse tail genotyping. This study was supported by the Cure Alzheimer's Fund, grants from the NIA, NIMH (R.E.T.), and the American Health Assistance Foundation (J.S.). NR 44 TC 51 Z9 52 U1 1 U2 18 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD OCT 16 PY 2013 VL 80 IS 2 BP 385 EP 401 DI 10.1016/j.neuron.2013.08.035 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 241VI UT WOS:000326196400020 PM 24055016 ER PT J AU Shah, NR Chokshi, DA AF Shah, Nirav R. Chokshi, Dave A. TI Should Health Care Systems Become Insurers? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID ORGANIZATIONS C1 [Shah, Nirav R.] New York State Dept Hlth, Albany, NY USA. [Chokshi, Dave A.] US Dept Vet Affairs, Washington, DC USA. RP Chokshi, DA (reprint author), Dept Vet Affairs, 810 Vermont Ave NW, Washington, DC 20006 USA. EM dave.chokshi@alumni.duke.edu OI Shah, Nirav/0000-0003-2044-7865; Chokshi, Dave/0000-0001-7467-4591 NR 6 TC 2 Z9 2 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 16 PY 2013 VL 310 IS 15 BP 1561 EP 1562 DI 10.1001/jama.2013.280015 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 234EP UT WOS:000325624800015 PM 24129460 ER PT J AU Li, N Lim, G Chen, L McCabe, MF Kim, H Zhang, SZ Mao, JR AF Li, Na Lim, Grewo Chen, Lucy McCabe, Michael F. Kim, Hyangin Zhang, Shuzhuo Mao, Jianren TI Spinal expression of Hippo signaling components YAP and TAZ following peripheral nerve injury in rats SO BRAIN RESEARCH LA English DT Article DE Neuropathic pain; Hippo signaling pathway; Spinal cord; Dorsal horn; Proliferation; Dendrite; Synaptic plasticity; Structural plasticity ID GENE-RELATED PEPTIDE; CORD DORSAL-HORN; NEUROPATHIC PAIN; SENSORY NEURONS; ADULT-RAT; CENTRAL SENSITIZATION; CONSTRICTION INJURY; DEPENDENT MECHANISM; NEGATIVE REGULATION; CELL-PROLIFERATION AB Previous studies have shown that the morphology and number of cells in the spinal cord dorsal horn could change following peripheral nerve injury and that the Hippo signaling pathway plays an important role in cell growth, proliferation, apoptosis, and dendritic remolding. In the present study, we examined whether the expression of YAP and TAZ, two critical components regulated by Hippo signaling, in the spinal cord dorsal horn would be altered by chronic constriction sciatic nerve injury (CCI). We found that (1) YAP was mainly expressed on CGRP- and IB4-immunoreactive primary afferent nerve terminals without noticeable expression on glial cells, whereas TAZ was mainly expressed on spinal cord second order neurons as well as microglia; (2) upregulation of YAP and TAZ expression followed two distinct temporal patterns after CCI, such that the highest expression of YAP and TAZ was on day 14 and day 1 after CCI, respectively; (3) there were also unique topographic patterns of YAP and TAZ distribution in the spinal cord dorsal horn consistent with their distinctive association with primary afferents and second order neurons; (4) changes in the YAP expression were selectively induced by CCI but not CFA-induced hindpaw inflammation; and (5) the number of nuclear profiles of TAZ expression was significantly increased after CCI, indicating translocation of TAZ from the cytoplasma to nucleus. These findings indicate that peripheral nerve injury induced time-dependent and region-specific changes in the spinal YAP and TAZ expression. A role for Hippo signaling in synaptic and structural plasticity is discussed in relation to the cellular mechanism of neuropathic pain. (C) 2013 Elsevier B.V. All rights reserved. C1 [Li, Na; Lim, Grewo; Chen, Lucy; McCabe, Michael F.; Kim, Hyangin; Zhang, Shuzhuo; Mao, Jianren] Harvard Univ, MGH Ctr Translat Pain Res, Dept Anesthesia Crit Care & Pain Med, Sch Med,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Li, Na] Chengdu Mil Command, Kunming Gen Hosp, Dept Anesthesiol, Kunming, Yunnan, Peoples R China. [Zhang, Shuzhuo] Beijing Inst Pharmacol & Toxicol, Beijing, Peoples R China. RP Mao, JR (reprint author), Harvard Univ, MGH Ctr Translat Pain Res, Dept Anesthesia Crit Care & Pain Med, Sch Med,Massachusetts Gen Hosp, Boston, MA 02114 USA. EM lina8346@yahoo.com; glim@partners.org; jmao@partners.org FU NIH [DE18214, DE022901, DE18538] FX This work was partially supported by NIH RO1 grants DE18214, DE022901 and DE18538. We thank Drs. Shuxing Wang and Zerong You for their technique support. NR 61 TC 3 Z9 3 U1 0 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD OCT 16 PY 2013 VL 1535 BP 137 EP 147 DI 10.1016/j.brainres.2013.08.049 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 236WY UT WOS:000325831400013 PM 23998984 ER PT J AU Hills, LB Masri, A Konno, K Kakegawa, W Lam, ATN Lim-Melia, E Chandy, N Hill, RS Partlow, JN Al-Saffar, M Nasir, R Stoler, JM Barkovich, AJ Watanabe, M Yuzaki, M Mochida, GH AF Hills, L. Benjamin Masri, Amira Konno, Kotaro Kakegawa, Wataru Lam, Anh-Thu N. Lim-Melia, Elizabeth Chandy, Nandini Hill, R. Sean Partlow, Jennifer N. Al-Saffar, Muna Nasir, Ramzi Stoler, Joan M. Barkovich, A. James Watanabe, Masahiko Yuzaki, Michisuke Mochida, Ganeshwaran H. TI Deletions in GRID2 lead to a recessive syndrome of cerebellar ataxia and tonic upgaze in humans SO NEUROLOGY LA English DT Article ID DELTA-2 GLUTAMATE-RECEPTOR; COGNITIVE-AFFECTIVE SYNDROME; MOTOR COORDINATION; SYNAPSE FORMATION; PURKINJE-CELLS; MUTANT MICE; HOT-SPOT; GENE; MALFORMATIONS; SUBUNIT AB Objective: To identify the genetic cause of a syndrome causing cerebellar ataxia and eye movement abnormalities. Methods: We identified 2 families with cerebellar ataxia, eye movement abnormalities, and global developmental delay. We performed genetic analyses including single nucleotide polymorphism genotyping, linkage analysis, array comparative genomic hybridization, quantitative PCR, and Sanger sequencing. We obtained eye movement recordings of mutant mice deficient for the ortholog of the identified candidate gene, and performed immunohistochemistry using human and mouse brain specimens. Results: All affected individuals had ataxia, eye movement abnormalities, most notably tonic upgaze, and delayed speech and cognitive development. Homozygosity mapping identified the disease locus on chromosome 4q. Within this region, a homozygous deletion of GRID2 exon 4 in the index family and compound heterozygous deletions involving GRID2 exon 2 in the second family were identified. Grid2-deficient mice showed larger spontaneous and random eye movements compared to wild-type mice. In developing mouse and human cerebella, GRID2 localized to the Purkinje cell dendritic spines. Brain MRI in 2 affected children showed progressive cerebellar atrophy, which was more severe than that of Grid2-deficient mice. Conclusions: Biallelic deletions of GRID2 lead to a syndrome of cerebellar ataxia and tonic upgaze in humans. The phenotypic resemblance and similarity in protein expression pattern between humans and mice suggest a conserved role for GRID2 in the synapse organization between parallel fibers and Purkinje cells. However, the progressive and severe cerebellar atrophy seen in the affected individuals could indicate an evolutionarily unique role for GRID2 in the human cerebellum. C1 [Hills, L. Benjamin; Lam, Anh-Thu N.; Hill, R. Sean; Partlow, Jennifer N.; Al-Saffar, Muna; Stoler, Joan M.; Mochida, Ganeshwaran H.] Boston Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Nasir, Ramzi] Boston Childrens Hosp, Div Dev Med, Boston, MA USA. [Partlow, Jennifer N.] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Partlow, Jennifer N.] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA USA. [Masri, Amira] Jordan Univ Hosp, Dept Pediat, Div Child Neurol, Amman, Jordan. [Konno, Kotaro; Watanabe, Masahiko] Hokkaido Univ, Grad Sch Med, Dept Anat, Sapporo, Hokkaido, Japan. [Kakegawa, Wataru; Yuzaki, Michisuke] Keio Univ, Sch Med, Dept Physiol, Tokyo 160, Japan. [Lim-Melia, Elizabeth; Chandy, Nandini] New York Med Coll, Dept Pediat, Valhalla, NY 10595 USA. [Al-Saffar, Muna] United Arab Emirates Univ, Fac Med & Hlth Sci, Dept Pediat, Al Ain, U Arab Emirates. [Nasir, Ramzi; Stoler, Joan M.; Mochida, Ganeshwaran H.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Barkovich, A. James] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Mochida, Ganeshwaran H.] Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Unit, Boston, MA 02114 USA. RP Mochida, GH (reprint author), Boston Childrens Hosp, Div Genet, Boston, MA 02115 USA. EM Ganesh.Mochida@childrens.harvard.edu RI Yuzaki, Michisuke/K-5328-2013 OI Yuzaki, Michisuke/0000-0002-5750-3544 FU NINDS [R01NS035129]; Fogarty International Center [R21TW008223]; NHGRI [U54 HG003067]; Simons Foundation; Dubai Harvard Foundation for Medical Research FX Supported by grants from NINDS (R01NS035129), the Fogarty International Center (R21TW008223), NHGRI (U54 HG003067), the Simons Foundation, and the Dubai Harvard Foundation for Medical Research. NR 35 TC 26 Z9 27 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD OCT 15 PY 2013 VL 81 IS 16 BP 1378 EP 1386 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AA0ET UT WOS:000330769000006 PM 24078737 ER PT J AU De Luca, G van't Hof, AWJ Huber, K Gibson, M Bellandi, F Arntz, HR Maioli, M Noc, M Zorman, S Zeymer, U Gabriel, HM Emre, A Cutlip, D Rakowski, T Gyongyosi, M Dudek, D AF De Luca, Giuseppe van't Hof, Arnoud W. J. Huber, Kurt Gibson, C. Michael Bellandi, Francesco Arntz, Hans-Richard Maioli, Mauro Noc, Marko Zorman, Simona Zeymer, Uwe Gabriel, H. Mesquita Emre, Ayse Cutlip, Donald Rakowski, Tomasz Gyongyosi, Maryann Dudek, Dariusz CA Egypt Cooperation TI Impact of Hypertension on Distal Embolization, Myocardial Perfusion, and Mortality in Patients With ST Segment Elevation Myocardial Infarction Undergoing Primary Angioplasty SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ARTERIAL-BLOOD PRESSURE; RANDOMIZED-TRIAL; THROMBOLYSIS; REPERFUSION; THERAPY AB Hypertension is a well-known risk factor for atherosclerosis. However, data on the impact of hypertension in patients with ST elevation myocardial infarction (STEMI) are inconsistent and mainly related to studies performed in the thrombolytic era, with very few data on patients undergoing primary angioplasty. The aim of the present study was to evaluate the impact of hypertension on distal embolization, myocardial perfusion, and mortality in patients with STEMI undergoing primary percutaneous coronary intervention. Our population is represented by 1,662 patients undergoing primary angioplasty for STEMI included in the Early Glycoprotein IIb-IIIa inhibitors in Primary angioplasty database. Myocardial perfusion was evaluated by myocardial blush grade and ST segment resolution. Follow-up data were collected within 1 year after primary angioplasty. Hypertension was observed in 700 patients (42.1%). Hypertension was associated with more advanced age (p <0.001), female gender (p <0.001), diabetes (p <0.001), hypercholesterolemia (p <0.001), previous revascularization (p <0.001), anterior myocardial infarction (p = 0.006), longer ischemia time (p = 0.03), more extensive coronary artery disease (p = 0.002), more often treated with abciximab (p <0.001), and less often smokers (p <0.001). Hypertension was associated with impaired postprocedural myocardial blush grade 2 to 3 (68.2% vs 74.2%, p = 0.019) and complete ST segment resolution (51.7% vs 61.1%, p = 0.001). By a mean follow-up of 206 +/- 158 days, 70 patients (4.3%) had died. Hypertension was associated with a greater mortality (6.2% vs 2.9%, hazard ratio 2.31, 95% confidence interval 1.42 to 3.73, p <0.001), confirmed after correction for baseline confounding factors (hazard ratio 1.82, 95% confidence interval 1.03 to 3.22, p <0.001). In conclusion, this study showed that among patients with STEMI undergoing primary angioplasty, hypertension is associated with impaired reperfusion and independently predicts 1-year mortality. (C) 2013 Elsevier Inc. All rights reserved. C1 [De Luca, Giuseppe] Eastern Piedmont Univ, Maggiore della Carita Hosp, Div Cardiol, Novara, Italy. [van't Hof, Arnoud W. J.] Hosp Weezenlanden, Div Cardiol, Zwolle, Netherlands. [Huber, Kurt] Wilhelminenspital Stadt Wien, Dept Med Cardiol & Emergency Med 3, Vienna, Austria. [Gibson, C. Michael] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Bellandi, Francesco; Maioli, Mauro] Prato Hosp, Div Cardiol, Prato, Italy. [Arntz, Hans-Richard] Charite, Med Klin 2, Berlin, Germany. [Noc, Marko; Zorman, Simona] Univ Med Ctr, Ctr Intens Internal Med, Ljubljana, Slovenia. [Zeymer, Uwe] Herzzentrum Ludwigshafen, Div Cardiol, Ludwigshafen, Germany. [Gabriel, H. Mesquita] Hosp Santa Maria, Div Cardiol, Lisbon, Portugal. [Emre, Ayse] Siyami Ersek Thorac & Cardiovasc Surg Ctr, Istanbul, Turkey. [Cutlip, Donald] Beth Israel Deaconess Med Ctr, Intervent Cardiol Sect, Boston, MA 02215 USA. [Rakowski, Tomasz; Dudek, Dariusz] Jagiellonian Univ, Dept Cardiol 2, Inst Cardiol, Krakow, Poland. [Dudek, Dariusz] Med Univ Vienna, Dept Cardiol, Vienna, Austria. RP De Luca, G (reprint author), Eastern Piedmont Univ, Maggiore della Carita Hosp, Div Cardiol, Novara, Italy. EM giuseppe.deluca@maggioreosp.novara.it NR 20 TC 7 Z9 7 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 15 PY 2013 VL 112 IS 8 BP 1083 EP 1086 DI 10.1016/j.amjcard.2013.05.053 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 236XV UT WOS:000325833700005 PM 23910428 ER PT J AU Colilla, S Crow, A Petkun, W Singer, DE Simon, T Liu, XC AF Colilla, Susan Crow, Ann Petkun, William Singer, Daniel E. Simon, Teresa Liu, Xianchen TI Estimates of Current and Future Incidence and Prevalence of Atrial Fibrillation in the US Adult Population SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PROJECTIONS; RISK AB Estimates and projections of diagnosed incidence and prevalence of atrial fibrillation (AF) in the United States have been highly inconsistent across published studies. Although it is generally acknowledged that AF incidence and prevalence are increasing due to growing numbers of older people in the U.S. population, estimates of the rate of expected growth have varied widely. Reasons for these variations include differences in study design, covered time period, birth cohort, and temporal effects, as well as improvements in AF diagnosis due to increased use of diagnostic tools and health care awareness. The objective of this study was to estimate and project the incidence and prevalence of diagnosed AF in the United States out to 2030. A large health insurance claims database for the years 2001 to 2008, representing a geographically diverse 5% of the U.S. population, was used in this study. The trend and growth rate in AF incidence and prevalence was projected by a dynamic age-period cohort simulation progression model that included all diagnosed AF cases in future prevalence projections regardless of follow-up treatment, as well as those cases expected to be chronic in nature. Results from the model showed that AF incidence will double, from 1.2 million cases in 2010 to 2.6 million cases in 2030. Given this increase in incidence, AF prevalence is projected to increase from 5.2 million in 2010 to 12.1 million cases in 2030. The effect of uncertainty in model parameters was explored in deterministic and probabilistic sensitivity analyses. Variability in future trends in AF incidence and recurrence rates has the greatest impact on the projected estimates of chronic AF prevalence. It can be concluded that both incidence and prevalence of AF are likely to rise from 2010 to 2030, but there exists a wide range of uncertainty around the magnitude of future trends. (C) 2013 Elsevier Inc. All rights reserved. C1 [Colilla, Susan] Bristol Myers Squibb Co, Global Hlth Econ & Outcomes Res, Princeton, NJ USA. [Crow, Ann] Bristol Myers Squibb Co, Global Epidemiol Forecasting, Princeton, NJ USA. [Petkun, William] Bristol Myers Squibb Co, Global Med Affairs, Princeton, NJ 08540 USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Simon, Teresa] Bristol Myers Squibb Co, Global Pharmacovigilance & Epidemiol, New York, NY 10154 USA. [Liu, Xianchen] Pfizer Inc, Global Hlth Econ & Outcomes Res, New York, NY USA. RP Petkun, W (reprint author), Bristol Myers Squibb Co, Global Med Affairs, Princeton, NJ 08540 USA. EM william.petkun@bms.com FU Bristol-Myers Squibb; Pfizer Inc. FX This study was supported by a grant from Bristol-Myers Squibb and Pfizer Inc. NR 10 TC 146 Z9 148 U1 0 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 15 PY 2013 VL 112 IS 8 BP 1142 EP 1147 DI 10.1016/j.amjcard.2013.05.063 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 236XV UT WOS:000325833700014 PM 23831166 ER PT J AU Hayes, JH Barry, MJ McMahon, PM AF Hayes, Julia H. Barry, Michael J. McMahon, Pamela M. TI Observation Versus Initial Treatment for Prostate Cancer RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Hayes, Julia H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hayes, Julia H.; McMahon, Pamela M.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Hayes, Julia H.; Barry, Michael J.; McMahon, Pamela M.] Harvard Univ, Sch Med, Boston, MA USA. [Barry, Michael J.] Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. RP Hayes, JH (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. FU NCI NIH HHS [R25 CA092203, L30 CA124353] NR 1 TC 2 Z9 2 U1 0 U2 1 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 OCT 15 PY 2013 VL 159 IS 8 BP 574 EP 574 DI 10.7326/0003-4819-159-8-201310150-00016 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 249BH UT WOS:000326751200025 PM 24126653 ER PT J AU Smucny, J Tregellas, J AF Smucny, Jason Tregellas, Jason TI Nicotinic modulation of intrinsic brain networks in Schizophrenia SO BIOCHEMICAL PHARMACOLOGY LA English DT Review DE Schizophrenia; Nicotinic; Salience network; Default network; Small-world network ID ANTERIOR CINGULATE CIRCUITS; RESTING-STATE NETWORKS; DEFAULT MODE NETWORK; SMALL-WORLD NETWORKS; SUBUNIT GENE CHRNA7; ACETYLCHOLINE-RECEPTOR; FUNCTIONAL CONNECTIVITY; ALLOSTERIC MODULATORS; PARTIAL DUPLICATION; CIGARETTE-SMOKING AB The nicotinic receptor is a promising drug target currently being investigated for the treatment of cognitive symptoms in schizophrenia. A key step in this process is the development of noninvasive functional neuroimaging biomarkers that can be used to determine if nicotinic agents are eliciting their targeted biological effect, ideally through modulation of a fundamental aspect of neuronal function. To that end, neuroimaging researchers are beginning to understand how nicotinic modulation affects "intrinsic" brain networks to elicit potentially therapeutic effects. An intrinsic network is a functionally and (often) structurally connected network of brain areas whose activity reflects a fundamental neurobiological organizational principle of the brain. This review summarizes findings of the effects of nicotinic drugs on three topics related to intrinsic brain network activity: (1) the default mode network, a group of brain areas for which activity is maximal at rest and reduced during cognitive tasks, (2) the salience network, which integrates incoming sensory data with prior internal representations to guide future actions and change predictive values, and (3) multi-scale complex network dynamics, which describe these brain's ability to efficiency integrate information while preserving local functional specialization. These early findings can be used to inform future neuroimaging studies that examine the network effects of nicotinic agents. (C) 2013 Elsevier Inc. All rights reserved. C1 [Smucny, Jason; Tregellas, Jason] Univ Colorado, Neurosci Program, Aurora, CO 80045 USA. [Smucny, Jason; Tregellas, Jason] Univ Colorado, Dept Psychiat, Aurora, CO 80045 USA. [Smucny, Jason; Tregellas, Jason] Denver VA Med Ctr, Res Serv, Denver, CO 80220 USA. RP Smucny, J (reprint author), Univ Colorado, Neurosci Program, Anschutz Med Campus, Aurora, CO 80045 USA. EM Jason.smucny@ucdenver.edu; Jason.tregellas@ucdenver.edu RI Tregellas, Jason/J-3637-2015; OI Smucny, Jason/0000-0001-5656-7987 FU NIMH NIH HHS [F31 MH102879] NR 124 TC 7 Z9 7 U1 3 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 EI 1873-2968 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD OCT 15 PY 2013 VL 86 IS 8 SI SI BP 1163 EP 1172 DI 10.1016/j.bcp.2013.06.011 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 239FC UT WOS:000326007000015 PM 23796751 ER PT J AU Fetterman, JL Zelickson, BR Johnson, LW Moellering, DR Westbrook, DG Pompilius, M Sammy, MJ Johnson, M Dunham-Snary, KJ Cao, XM Bradley, WE Zhang, JJ Wei, CC Chacko, B Schurr, TG Kesterson, RA Dell'Italia, LJ Darley-Usmar, VM Welch, DR Ballinger, SW AF Fetterman, Jessica L. Zelickson, Blake R. Johnson, Larry W. Moellering, Douglas R. Westbrook, David G. Pompilius, Melissa Sammy, Melissa J. Johnson, Michelle Dunham-Snary, Kimberly J. Cao, Xuemei Bradley, Wayne E. Zhang, Jinju Wei, Chih-Chang Chacko, Balu Schurr, Theodore G. Kesterson, Robert A. Dell'Italia, Louis J. Darley-Usmar, Victor M. Welch, Danny R. Ballinger, Scott W. TI Mitochondrial genetic background modulates bioenergetics and susceptibility to acute cardiac volume overload SO BIOCHEMICAL JOURNAL LA English DT Article DE bioenergetics; disease susceptibility; mitochondria; mtDNA; oxidative stress ID NICOTINAMIDE NUCLEOTIDE TRANSHYDROGENASE; OXYGEN SPECIES PRODUCTION; CORONARY-HEART-DISEASE; CARDIOVASCULAR-DISEASE; SMOKE EXPOSURE; ATHEROSCLEROSIS SUSCEPTIBILITY; C57BL/6J MICE; MOUSE; DNA; NUCLEAR AB Dysfunctional bioenergetics has emerged as a key feature in many chronic pathologies such as diabetes and cardiovascular disease. This has led to the mitochondrial paradigm in which it has been proposed that mtDNA sequence variation contributes to disease susceptibility. In the present study we show a novel animal model of mtDNA polymorphisms, the MNX (mitochondrial nuclear exchange) mouse, in which the mtDNA from the C3H/HeN mouse has been inserted on to the C57/BL6 nuclear background and vice versa to test this concept. Our data show a major contribution of the C57/BL6 mtDNA to the susceptibility to the pathological stress of cardiac volume overload which is independent of the nuclear background. Mitochondria harbouring the C57/BL6J mtDNA generate more ROS (reactive oxygen species) and have a higher mitochondrial membrane potential relative to those with C3H/HeN mtDNA, independent of nuclear background. We propose this is the primary mechanism associated with increased bioenergetic dysfunction in response to volume overload. In summary, these studies support the 'mitochondrial paradigm' for the development of disease susceptibility, and show that the mtDNA modulates cellular bioenergetics, mitochondrial ROS generation and susceptibility to cardiac stress. C1 [Fetterman, Jessica L.; Zelickson, Blake R.; Westbrook, David G.; Pompilius, Melissa; Sammy, Melissa J.; Johnson, Michelle; Dunham-Snary, Kimberly J.; Chacko, Balu; Darley-Usmar, Victor M.; Ballinger, Scott W.] Univ Alabama Birmingham, Div Mol & Cellular Pathol, Birmingham, AL 35294 USA. [Fetterman, Jessica L.; Zelickson, Blake R.; Moellering, Douglas R.; Sammy, Melissa J.; Dunham-Snary, Kimberly J.; Chacko, Balu; Dell'Italia, Louis J.; Darley-Usmar, Victor M.; Ballinger, Scott W.] Univ Alabama Birmingham, Ctr Free Rad Biol, Birmingham, AL 35294 USA. [Johnson, Larry W.; Zhang, Jinju; Kesterson, Robert A.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA. [Moellering, Douglas R.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Cao, Xuemei; Welch, Danny R.] Univ Kansas, Ctr Canc, Dept Canc Biol, Kansas City, KS 66160 USA. [Bradley, Wayne E.; Wei, Chih-Chang; Dell'Italia, Louis J.] Univ Alabama Birmingham, Div Cardiol, Birmingham, AL 35294 USA. [Schurr, Theodore G.] Univ Penn, Dept Anthropol, Philadelphia, PA 19104 USA. [Dell'Italia, Louis J.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. RP Welch, DR (reprint author), Univ Kansas, Ctr Canc, Dept Canc Biol, Kansas City, KS 66160 USA. EM dwelch@kumc.edu; sballing@uab.edu OI Sammy, Melissa/0000-0002-5460-0963 FU National Institutes for Health [RO1 94518, RO1 103859]; National Foundation for Cancer Research; Susan G. Komen for the Cure [SAC111370]; U.S. Army Medical Research & Material Command [W81XWH-07-1-0540d]; University of Alabama at Birmingham Comprehensive Cancer Center [CA013148]; National Institutes of Health [RO1 HL109785, P30 CA13148, P30 AR048311, P30 DK074038, P30 DK05336, P60 DK079626]; a National Institutes of Health predoctoral training programme in cardiovascular pathophysiology [T32 HL007918]; American Heart Association [09PRE2240046, 11PRE7650033]; Diabetes Research Center Bioanalytical Redox Biology Core [P60 DK079626] FX This work was funded by the National Institutes for Health [grant numbers RO1 94518 and RO1 103859 (to S.W.B.)], the National Foundation for Cancer Research (to D.R.W.), Susan G. Komen for the Cure [grant number SAC111370 (to D.R.W.)], U.S. Army Medical Research & Material Command [grant number W81XWH-07-1-0540d (to S.W.B.)] and a pilot grant from the University of Alabama at Birmingham Comprehensive Cancer Center [grant number CA013148 (to D.R.W. and S.W.B.)]. Additional support was received from the National Institutes of Health [grant number RO1 HL109785 (to L.J.D.)), a National Institutes of Health predoctoral training programme in cardiovascular pathophysiology [grant number T32 HL007918 (to J.L.F.)], American Heart Association predoctoral fellowships [numbers 09PRE2240046 (to J.L.F.) and 11PRE7650033 (to K.J.D.)). The University of Alabama at Birmingham Transgenic Mouse Facility (RAK) is supported by the National Institutes of Health [grant numbers P30 CA13148, P30 AR048311, P30 DK074038, P30 DK05336 and P60 DK079626] and by the National Institutes of Health-funded Diabetes Research Center Bioanalytical Redox Biology Core [grant number P60 DK079626) located at the University of Alabama at Birmingham. NR 66 TC 20 Z9 20 U1 2 U2 12 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD OCT 15 PY 2013 VL 455 BP 157 EP 167 DI 10.1042/BJ20130029 PN 2 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 243ZV UT WOS:000326357800003 PM 23924350 ER PT J AU Blower, MD Jambhekar, A Schwarz, DS Toombs, JA AF Blower, Michael D. Jambhekar, Ashwini Schwarz, Dianne S. Toombs, James A. TI Combining Different mRNA Capture Methods to Analyze the Transcriptome: Analysis of the Xenopus laevis Transcriptome SO PLOS ONE LA English DT Article ID MAJOR DEVELOPMENTAL TRANSITION; TRANSLATIONAL CONTROL; NONCODING RNAS; REVEALS; LENGTH; EXPRESSION; TROPICALIS; LINCRNAS; GENOME; POLYADENYLATION AB mRNA sequencing (mRNA-seq) is a commonly used technique to survey gene expression from organisms with fully sequenced genomes. Successful mRNA-seq requires purification of mRNA away from the much more abundant ribosomal RNA, which is typically accomplished by oligo-dT selection. However, mRNAs with short poly-A tails are captured poorly by oligo-dT based methods. We demonstrate that combining mRNA capture via oligo-dT with mRNA capture by the 5' 7-methyl guanosine cap provides a more complete view of the transcriptome and can be used to assay changes in mRNA poly-A tail length on a genome-wide scale. We also show that using mRNA-seq reads from both capture methods as input for de novo assemblers provides a more complete reconstruction of the transcriptome than either method used alone. We apply these methods of mRNA capture and de novo assembly to the transcriptome of Xenopus laevis, a well-studied frog that currently lacks a finished sequenced genome, to discover transcript sequences for thousands of mRNAs that are currently absent from public databases. The methods we describe here will be broadly applicable to many organisms and will provide insight into the transcriptomes of organisms with sequenced and unsequenced genomes. C1 [Blower, Michael D.; Jambhekar, Ashwini; Schwarz, Dianne S.; Toombs, James A.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Blower, Michael D.; Jambhekar, Ashwini; Schwarz, Dianne S.; Toombs, James A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Blower, MD (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM blower@molbio.mgh.harvard.edu NR 44 TC 4 Z9 4 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 15 PY 2013 VL 8 IS 10 AR e77700 DI 10.1371/journal.pone.0077700 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 237TP UT WOS:000325894100096 PM 24143257 ER PT J AU McCarthy, AM Bristol, M Fredricks, T Wilkins, L Roelfsema, I Liao, KJ Shea, JA Groeneveld, P Domchek, SM Armstrong, K AF McCarthy, Anne Marie Bristol, Mirar Fredricks, Tracey Wilkins, Lache Roelfsema, Irene Liao, Kaijun Shea, Judy A. Groeneveld, Peter Domchek, Susan M. Armstrong, Katrina TI Are Physician Recommendations for BRCA1/2 Testing in Patients With Breast Cancer Appropriate? A Population-Based Study SO CANCER LA English DT Article DE breast cancer; genetic testing; BRCA1; 2; physician recommendations; cancer registry ID MUTATION CARRIERS; WOMEN; RISK; DECISIONS; KNOWLEDGE; ATTITUDES; FAMILIES; COVERAGE; SURGERY AB BACKGROUNDTo the best of the authors' knowledge, few population-based studies to date have examined the use of BRCA1/2 testing or patterns of physician recommendations for genetic testing among women diagnosed with breast cancer. The objective of the current study was to evaluate the rates and predictors of physician recommendation for BRCA1/2 testing among patients with breast cancer. METHODSWomen aged 18 years to 64 years who were diagnosed with invasive breast cancer in 2007 were identified from the Pennsylvania Cancer Registry and mailed a survey regarding their family history of cancer, physician treatment recommendations, and BRCA1/2 testing. Of the 4009 women who were sent surveys, 2258 responded (56%). Based on age at diagnosis and family history, women were categorized as being at high, moderate, or low risk of BRCA1/2 mutations. RESULTSNearly 25% of the participants were classified as being at high risk of carrying a BRCA1/2 mutation based on their age at the time of breast cancer diagnosis and family history of breast and/or ovarian cancer. Physician recommendations for BRCA1/2 testing were found to be strongly associated with risk of carrying a mutation, with 53% of high-risk women reporting a testing recommendation compared with 9% of low-risk women. In addition, physician recommendations were strongly correlated with the use of testing in all risk groups. Among high-risk women, the lack of a recommendation for BRCA1/2 testing was more common among older, low-income, and employed women. CONCLUSIONSAlthough BRCA1/2 testing recommendations appear to be appropriately correlated with mutation risk, a significant percentage of patients with breast cancer who meet criteria for BRCA1/2 testing may not receive a recommendation for such testing from their health care providers. Cancer 2013;119:3596-3603. (c) 2013 American Cancer Society. C1 [McCarthy, Anne Marie; Bristol, Mirar; Fredricks, Tracey; Wilkins, Lache; Roelfsema, Irene; Liao, Kaijun; Shea, Judy A.; Groeneveld, Peter; Domchek, Susan M.; Armstrong, Katrina] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Groeneveld, Peter] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Domchek, Susan M.; Armstrong, Katrina] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP McCarthy, AM (reprint author), Univ Penn, 423 Guardian Dr,Room 1009, Philadelphia, PA 19104 USA. EM annemcc@mail.med.upenn.edu FU National Institutes of Health grant from the National Cancer Institute [5-R01-CA133004-3] FX Supported by a National Institutes of Health grant from the National Cancer Institute (5-R01-CA133004-3). NR 25 TC 7 Z9 7 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD OCT 15 PY 2013 VL 119 IS 20 BP 3596 EP 3603 DI 10.1002/cncr.28268 PG 8 WC Oncology SC Oncology GA 230WJ UT WOS:000325373700039 PM 23861169 ER PT J AU Skolarus, TA Chan, S Shelton, JB Antonio, AL Sales, AE Malin, JL Saigal, CS AF Skolarus, Ted A. Chan, Stephanie Shelton, Jeremy B. Antonio, Anna Liza Sales, Anne E. Malin, Jennifer L. Saigal, Christopher S. TI Quality of Prostate Cancer Care Among Rural Men in the Veterans Health Administration SO CANCER LA English DT Article DE prostate cancer; quality; rural; integrated delivery system; access ID RADIATION-THERAPY; ANDROGEN SUPPRESSION; ACCESS; ADENOCARCINOMA; BARRIERS; TRIAL; RISK; TERM; VA AB BACKGROUNDPatient travel distances, coupled with variation in facility-level resources, create barriers for prostate cancer care in the Veterans Health Administration integrated delivery system. For these reasons, the authors investigated the degree to which these barriers impact the quality of prostate cancer care. METHODSThe Veterans Affairs Central Cancer Registry was used to identify all men who were diagnosed with prostate cancer in 2008. Patient residence was characterized using Rural Urban Commuting Area codes. The authors then examined whether rural residence, compared with urban residence, was associated with less access to cancer-related resources and worse quality of care for 5 prostate cancer quality measures. RESULTSApproximately 25% of the 11,368 patients who were diagnosed with prostate cancer in 2008 lived in either a rural area or a large town. Rural patients tended to be white (62% urban vs 86% rural) and married (47% urban vs 63% rural), and they tended to have slightly higher incomes (all P<.01) but similar tumor grade (P=.23) and stage (P=.12) compared with urban patients. Rural patients were significantly less likely to be treated at facilities with comprehensive cancer resources, although they received a similar or better quality of care for 4 of the 5 prostate cancer quality measures. The time to prostate cancer treatment was similar (rural patients vs urban patients, 96.6 days vs 105.7 days). CONCLUSIONSRural patients with prostate cancer had less access to comprehensive oncology resources, although they received a similar quality of care, compared with their urban counterparts in the Veterans Health Administration integrated delivery system. A better understanding of the degree to which facility factors contribute to the quality of cancer care may assist other organizations involved in rural health care delivery. Cancer 2013;119:3629-3635. (c) 2013 American Cancer Society. C1 [Skolarus, Ted A.; Sales, Anne E.] Vet Affairs Ann Arbor Healthcare Syst, Hlth Serv Res & Dev Serv, Ctr Clin Management Res, Ann Arbor, MI USA. [Skolarus, Ted A.] Univ Michigan, Dow Div Hlth Serv Res, Dept Urol, Ann Arbor, MI 48109 USA. [Chan, Stephanie] Frederick S Pardee RAND Grad Sch, Santa Monica, CA USA. [Shelton, Jeremy B.; Antonio, Anna Liza; Malin, Jennifer L.; Saigal, Christopher S.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Shelton, Jeremy B.; Saigal, Christopher S.] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. [Sales, Anne E.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. [Malin, Jennifer L.] Wellpoint Inc, Med Oncol, Indianapolis, IN USA. RP Skolarus, TA (reprint author), Univ Michigan, Dept Urol, VA Ctr Clin Management Res, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48109 USA. EM tskolar@med.umich.edu OI Sales, Anne/0000-0001-9360-3334 FU Veterans Health Administration Office of Analytics and Business Intelligence; VA HSR&D Career Development Award - 2 [CDA 12-171] FX This work was supported by the Veterans Health Administration Office of Analytics and Business Intelligence "Supportive Care, End of Life Care, and Crosscutting Quality Indicators for Patients with Cancer Within VA" Project. Dr. Skolarus is supported by a VA HSR&D Career Development Award - 2 (CDA 12-171). NR 33 TC 7 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD OCT 15 PY 2013 VL 119 IS 20 BP 3629 EP 3635 DI 10.1002/cncr.28275 PG 7 WC Oncology SC Oncology GA 230WJ UT WOS:000325373700043 PM 23913676 ER PT J AU Aggarwal, R Halabi, S Kelly, WK George, D Mahoney, JF Millard, F Stadler, WM Morris, MJ Kantoff, P Monk, JP Carducci, M Small, EJ AF Aggarwal, Rahul Halabi, Susan Kelly, William Kevin George, Daniel Mahoney, John F. Millard, Frederick Stadler, Walter M. Morris, Michael J. Kantoff, Philip Monk, J. Paul Carducci, Michael Small, Eric J. CA Alliance Clinical Trials Oncology TI The Effect of Prior Androgen Synthesis Inhibition on Outcomes of Subsequent Therapy With Docetaxel in Patients With Metastatic Castrate-Resistant Prostate Cancer SO CANCER LA English DT Article DE prostatic neoplasms; chemotherapy; ketoconazole; steroid 17-alpha-hydroxylase; androgen antagonists ID ANTITUMOR-ACTIVITY; INCREASED SURVIVAL; KETOCONAZOLE; PREDNISONE; TRIAL; MITOXANTRONE; ABIRATERONE; MEN; BIOSYNTHESIS; CHEMOTHERAPY AB BACKGROUNDPreliminary data suggest a potential decreased benefit of docetaxel in patients with metastatic, castration-resistant prostate cancer (mCRPC) who previously received abiraterone acetate, a novel androgen synthesis inhibitor (ASI). Cancer and Leukemia Group B (CALGB) trial 90401 (Alliance), a phase 3 trial in patients with mCRPC who received docetaxel-based chemotherapy, offered the opportunity to evaluate effect of prior ketoconazole, an earlier generation ASI, on clinical outcomes after docetaxel. METHODSIn CALGB trial 90401, 1050 men with chemotherapy-naive mCRPC were randomized to receive treatment with docetaxel and prednisone that included either bevacizumab or placebo. In total, 1005 men (96%) had data available regarding prior ketoconazole therapy. The observed effects of prior ketoconazole on overall survival (OS), progression-free survival (PFS), prostate-specific antigen (PSA) decline, and the objective response rate (ORR) were assessed using proportional hazards and Poisson regression methods adjusted for validated prognostic factors and treatment arm. RESULTSBaseline characteristics between patients who did (N=277) and did not (N=728) receive prior ketoconazole therapy were similar. There were no statistically significant differences between patients who did and those who did not receive prior ketoconazole therapy with respect to OS (median OS, 21.1 months vs 22.3 months, respectively; stratified log-rank P=.635), PFS (median PFS, 8.1 months vs 8.6 months, respectively; stratified log-rank P=.342), the proportion achieving a decline 50% in PSA (61% vs 66%, respectively; relative risk, 1.09; adjusted P=.129), or ORR (39% vs 43%, respectively; relative risk, 1.11; adjusted P=.366). CONCLUSIONSAs measured by OS, PFS, PSA, and the ORR, there was no evidence that prior treatment with ketoconazole had an impact on the clinical outcomes of patients with mCRPC who received subsequent docetaxel-based therapy. The current results highlight the need for prospective studies to assess for potential cross-resistance with novel ASIs and to define the optimal sequence of therapy in mCRPC. Cancer 2013;119:3636-3643. (c) 2013 American Cancer Society. C1 [Aggarwal, Rahul] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Div Hematol Oncol, San Francisco, CA 94143 USA. [Halabi, Susan] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. [Halabi, Susan] Duke Univ, Med Ctr, Alliance Stat & Data Ctr, Durham, NC USA. [Kelly, William Kevin] Thomas Jefferson Univ, Dept Med Oncol, Philadelphia, PA 19107 USA. [George, Daniel] Duke Univ, Med Ctr, Dept Med Oncol, Durham, NC USA. [Mahoney, John F.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Millard, Frederick] Univ Calif San Diego, Div Hematol Oncol, San Diego, CA 92103 USA. [Stadler, Walter M.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. [Morris, Michael J.] Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, New York, NY 10021 USA. [Kantoff, Philip] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Monk, J. Paul] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. [Carducci, Michael] Johns Hopkins Univ, Dept Oncol & Urol, Baltimore, MD USA. [Small, Eric J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Dept Med & Urol, San Francisco, CA 94143 USA. RP Aggarwal, R (reprint author), Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, 1600 Divisadero,3rd Floor, San Francisco, CA 94143 USA. EM rahul.aggarwal@ucsf.edu FU National Cancer Institute (NCI) [CA31946, CA60138, CA33601, CA13650, CA7577, CA5808, CA11789, CA41287, CA77651, CA32291, CA77658, CA16116, CA45418, CA04326, CA47577, CA29165]; NCI [CA114558, CA45389, CA35113, CA114558-02, CA35279, CA45564, CA04457, CA35421, CA86726, CA08025, CA59518, CA45808, CA21060, CA74811, CA47642, CA31983, CA16450, CA77298, CA47559, CA37447, CA77406, CA77440, CA07968, CA16359] FX The research for CALGB 90401 (Alliance) was supported in part by grants from the National Cancer Institute (NCI) to the Alliance for Clinical Trials in Oncology (Monica M. Bertagnolli, MD, Chair; grant CA31946) and to the Alliance Statistics and Data Center (Daniel J. Sargent, PhD; grant CA33601).; Drs. Aggarwal and Small were supported by NCI grant CA60138; Dr. Halabi was supported by NCI grant CA33601; Dr. Kelly was supported by NCI grant CA13650; Dr. George was supported by NCI grant CA7577; Dr. Mahoney was supported by NCI grant CA5808; Dr. Millard was supported by NCI grant CA11789; Dr. Stadler was supported by NCI grant CA41287; Dr. Morris was supported by NCI grant CA77651; Dr. Kantoff was supported by NCI grant CA32291; Dr. Monk was supported by NCI grant CA77658; and Dr. Carducci was supported by NCI grant CA16116.; The following institutions participated in this study: Alliance Statistics and Data Center, Duke University Medical Center, Durham, NC (Daniel J. Sargent, PhD; supported by NCI grant CA33601); Christiana Care Health Services, Inc. Community Clinical Oncology Program (CCOP), Wilmington, Del (Stephen Grubbs, MD; supported by CA45418); Dana-Farber Cancer Institute, Boston, Mass (Harold J. Burstein, MD, PhD; supported by CA32291); Dartmouth Medical School-Norris Cotton Cancer Center, Lebanon, NH (Konstantin Dragnev, MD; supported by CA04326); Duke University Medical Center, Durham, NC (Jeffrey Crawford, MD; supported by CA47577); Greenville CCOP, Greenville, SC (Jeffrey Giguere, MD; supported by CA29165); Heartland Cancer Research CCOP, St. Louis, Mo (Alan P. Lyss, MD; supported by CA114558 to Missouri Baptist Medical Center); Hematology-Oncology Associates of Central New York CCOP, Syracuse, NY (Jeffrey Kirshner, MD; supported by CA45389); Illinois Oncology Research Association, Peoria, Ill (John W. Kugler, MD; supported by CA35113); Kansas City CCOP, Kansas City, Mo (Rakesh Gaur, MD); Massachusetts General Hospital, Boston, Mass (Jeffrey W. Clark, MD; supported by CA32291); Memorial Sloan-Kettering Cancer Center, New York, NY (Clifford A. Hudis, MD; supported by CA77651); Missouri Baptist Medical Center, St. Louis, Mo (Alan P. Lyss, MD; supported by CA114558-02 [a grant only to be used for studies that accrued patients after June 1, 2005; the institution received no grant before 2005, and Missouri was an at-large member]); Monter Cancer Center of North Shore-LIJ Health Systems, Lake Success, NY (Daniel Budman, MD; supported by CA35279); Mount Sinai Medical Center, Miami, Fla (Michael A. Schwartz, MD; supported by CA45564); Mount Sinai School of Medicine, New York, NY (Lewis R. Silverman, MD; supported by CA04457); Nevada Cancer Research Foundation CCOP, Las Vegas, Nev (John A. Ellerton, MD; supported by CA35421); New Hampshire Oncology-Hematology PA, Concord, NH (Douglas J. Weckstein, MD); North Shore University Health System CCOP, Evanston, Ill (David L. Grinblatt, MD); Northern Indiana Cancer Research Consortium CCOP, South Bend, Ind (Rafat Ansari, MD; supported by CA86726); Rhode Island Hospital, Providence, RI (William Sikov, MD; supported by CA08025); Roswell Park Cancer Institute, Buffalo, NY (Ellis Levine, MD; supported by CA59518); Sibley Memorial Hospital, Washington, DC (Frederick Barr, MD); Southeast Cancer Control Consortium Inc. CCOP, Goldsboro, NC (James N. Atkins, MD; supported by CA45808); State University of New York Upstate Medical University, Syracuse, NY (Stephen L. Graziano, MD; supported by CA21060); The Ohio State University Medical Center, Columbus, Ohio (Clara D. Bloomfield, MD; supported by CA77658); University of California at San Diego, San Diego, Calif (Barbara A. Parker, MD; supported by CA11789); University of California at San Francisco, San Francisco, Calif (Charles J. Ryan, MD; supported by CA60138); University of Chicago, Chicago, Ill (Hedy L. Kindler, MD; supported by CA41287); University of Illinois Minority-Based CCOP, Chicago, Ill (David J. Peace, MD; supported by CA74811); University of Iowa, Iowa City, Iowa (Daniel A. Vaena, MD; supported by CA47642); University of Maryland Greenebaum Cancer Center, Baltimore, MD (Martin Edelman, MD; supported by CA31983); University of Minnesota, Minneapolis, Minn (Bruce A.; Peterson, MD; supported by CA16450); University of Nebraska Medical Center, Omaha, Neb (Apar Ganti, MD; supported by CA77298); University of North Carolina at Chapel Hill, Chapel Hill, NC (Thomas C. Shea, MD; supported by CA47559); University of Oklahoma, Oklahoma City, Okla (Shubham Pant, MD; supported by CA37447); University of Vermont, Burlington, Vt (Steven M. Grunberg, MD; supported by CA77406); Washington University School of Medicine, St. Louis, Mo (Nancy Bartlett, MD; supported by CA77440); Weill Medical College of Cornell University, New York, NY (John Leonard, MD; supported by CA07968); Western Pennsylvania Cancer Institute, Pittsburgh, Pa, John Lister, MD); and Yale University, New Haven, Conn (Lyndsay N. Harris, MD; supported by CA16359). NR 25 TC 8 Z9 9 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD OCT 15 PY 2013 VL 119 IS 20 BP 3636 EP 3643 DI 10.1002/cncr.28285 PG 8 WC Oncology SC Oncology GA 230WJ UT WOS:000325373700044 PM 23913744 ER PT J AU Rauh-Hain, JA Clemmer, JT Bradford, LS Clark, RM Growdon, WB Goodman, A Boruta, DM Schorge, JO del Carmen, MG AF Rauh-Hain, J. Alejandro Clemmer, Joel T. Bradford, Leslie S. Clark, Rachel M. Growdon, Whitfield B. Goodman, Annekathryn Boruta, David M., II Schorge, John O. del Carmen, Marcela G. TI Racial Disparities in Cervical Cancer Survival Over Time SO CANCER LA English DT Article DE cervical cancer; African American; race; disparities; SEER ID ETHNIC-DIFFERENCES; AFRICAN-AMERICAN; UTERINE CERVIX; SEER DATA; WOMEN; STAGE; CARCINOMA; CARE; STATISTICS; RADIATION AB BACKGROUNDThe purpose of this study is to examine changes over time in survival for African American (AA) and white women diagnosed with cervical cancer (CC). METHODSSurveillance, Epidemiology, and End Results (SEER) Program data from 1985 to 2009 were used for this analysis. Racial differences in survival were evaluated between African American (AA) and white women. Kaplan-Meier and Cox proportional hazards survival methods were used to assess differences in survival by race at 5-year intervals. RESULTSThe study sample included 23,368 women, including 3886 (16.6%) who were AA and 19,482 (83.4%) who were white. AA women were older (51.4 versus 48.9 years; P<.001) and had a higher rate of regional (38.3% versus 31.8%; P<.001) and distant metastasis (10.7% versus 8.7%; P<.001). AA less frequently received cancer-directed surgery (32.4% versus 46%; P<.001), and more frequently radiotherapy (36.3% versus 26.4%; P<.001). Overall, AA women had a hazard ratio (HR) of 1.41 (95% confidence interval=1.32-1.51) of cervical cancer (CC) mortality compared with whites. Adjusting for SEER registry, marital status, stage, age, treatment, grade, and histology, AA women had an HR of 1.13 (95% confidence interval=1.05-1.22) of CC-related mortality. After adjusting for the same variables, there was a significant difference in CC-specific mortality between 1985 to 1989 and 1990 to 1994, but not after 1995. CONCLUSIONSAfter adjusting for race, SEER registry, marital status, stage, age, treatment, grade, and histology, there was a significant difference in CC-specific mortality between 1985 to 1989 and 1990 to 1994, but not after 1995. Cancer 2013;119:3644-3652. (c) 2013 American Cancer Society. C1 [Rauh-Hain, J. Alejandro; Clemmer, Joel T.; Bradford, Leslie S.; Clark, Rachel M.; Growdon, Whitfield B.; Goodman, Annekathryn; Boruta, David M., II; Schorge, John O.; del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA USA. RP del Carmen, MG (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA. EM mdelcarmen@partners.org NR 31 TC 12 Z9 12 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD OCT 15 PY 2013 VL 119 IS 20 BP 3644 EP 3652 DI 10.1002/cncr.28261 PG 9 WC Oncology SC Oncology GA 230WJ UT WOS:000325373700045 PM 23913530 ER PT J AU Evens, AM Vanderplas, A LaCasce, AS Crosby, AL Nademanee, AP Kaminski, MS Abel, GA Millenson, M Czuczman, MS Rodriguez, MA Niland, J Zelenetz, AD Gordon, LI Friedberg, JW AF Evens, Andrew M. Vanderplas, Ann LaCasce, Ann S. Crosby, Allison L. Nademanee, Auayporn P. Kaminski, Mark S. Abel, Gregory A. Millenson, Michael Czuczman, Myron S. Rodriguez, Maria A. Niland, Joyce Zelenetz, Andrew D. Gordon, Leo I. Friedberg, Jonathan W. TI Stem Cell Transplantation for Follicular Lymphoma Relapsed/Refractory After Prior Rituximab SO CANCER LA English DT Article DE follicular lymphoma; prognostication; autologous transplantation; allogeneic transplantation; survival; rituximab; non-Hodgkin lymphoma; stem cell transplantation ID NON-HODGKINS-LYMPHOMA; HIGH-DOSE THERAPY; BONE-MARROW-TRANSPLANTATION; TERM-FOLLOW-UP; PRETRANSPLANTATION TREATMENT; PROPENSITY-SCORE; SURVIVAL; REMISSION; IMPROVES; OUTCOMES AB BACKGROUNDStem cell transplant (SCT)-related outcomes and prognostication for relapsed/refractory follicular lymphoma (FL) are not well-defined in the post-rituximab era. METHODSThrough the National Comprehensive Cancer Network (NCCN) lymphoma outcomes study, 184 patients with relapsed/refractory FL who underwent autologous SCT (autoSCT) or allogenic SCT (alloSCT) following disease relapse after prior rituximab-based therapy were examined. RESULTSPatients who underwent autoSCT (N=136) were older compared with patients who underwent alloSCT (N=48) (54 versus 51 years, respectively, P=.01) and more frequently had grade 3 FL (35% versus 8%, respectively, P=.006). Patients who underwent alloSCT received more prior therapies (4 versus 3, respectively, P<.0001) and more often had resistant disease at SCT (19% versus 6%, respectively, P=.008). Cumulative 100-day nonrelapse mortality (NRM) for autoSCT and alloSCT were 1% and 6%, respectively (P<.0001), whereas 3-year NRM rates were 3% versus 24%, respectively (P<.0001). For autoSCT and alloSCT, cumulative rates of relapse, progression, and/or transformation were 32% versus 16%, respectively (P=.03), whereas 3-year overall survival rates were 87% versus 61% (P<.0001); there were no differences in failure-free survival. AlloSCT was associated with increased risk of death on multivariate analysis (hazard ratio=2.77, 95% confidence interval=1.46-5.26, P=.002). This finding persisted on propensity scoring/matching. Multivariate analysis for autoSCT patients identified age>60 years and>3 prior therapies as adverse factors. Furthermore, a survival model was created for the autoSCT cohort based on number of factors present (0, 1, 2); 3-year failure-free survival was 72%, 47%, and 20%, respectively (P=.0003), and 3-year overall survival was 96%, 82%, and 62%, respectively (P<.0001). CONCLUSIONSAutoSCT remains an effective therapy for patients with FL. For alloSCT, continued strategies to reduce NRM are needed. Cancer 2013;119:3662-3671. (c) 2013 American Cancer Society. C1 [Evens, Andrew M.] Tufts Univ, Sch Med, Div Hematol Oncol, Boston, MA 02111 USA. [Vanderplas, Ann; Niland, Joyce] City Hope Natl Med Ctr, Dept Biostat, Duarte, CA 91010 USA. [LaCasce, Ann S.; Crosby, Allison L.; Abel, Gregory A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Nademanee, Auayporn P.] City Hope Natl Med Ctr, Dept Stem Cell Transplant, Duarte, CA 91010 USA. [Kaminski, Mark S.] Univ Michigan, Ctr Canc, Ann Arbor, MI 48109 USA. [Millenson, Michael] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Czuczman, Myron S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Rodriguez, Maria A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Zelenetz, Andrew D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Gordon, Leo I.] Northwestern Univ, Div Hematol Oncol, Chicago, IL 60611 USA. [Friedberg, Jonathan W.] Univ Rochester, Div Hematol Oncol, James P Wilmot Canc Ctr, Rochester, NY USA. RP Evens, AM (reprint author), Tufts Univ, Sch Med, 800 Washington St, Boston, MA 02111 USA. EM AEvens@tuftsmedicalcenter.org FU National Comprehensive Cancer Network (NCCN); NCCN Data Outcomes; Pfizer; GlaxoSmithKline; Amgen; NCCN; Genentech; Roche FX Dr. Millenson has received support from a National Comprehensive Cancer Network (NCCN) grant. Dr. Czuczman has received a grant from NCCN Data Outcomes. Dr. Rodriguez has received grants for research funding from Pfizer, GlaxoSmithKline, and Amgen. Dr. Niland has received support from an NCCN contract with her institution for the Data Coordinating Center for the support of responsibility for data analysis for this article. Dr. Zelenetz has acted as a consultant for Genentech and Roche and has received grants from both to support unrelated trials. Dr. Friedberg has acted a member of the Trubion Data Safety Monitoring Committee, the Bayer Data Safety Monitoring Committee, and the Sanofi Advisory Board. NR 25 TC 22 Z9 22 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD OCT 15 PY 2013 VL 119 IS 20 BP 3662 EP 3671 DI 10.1002/cncr.28243 PG 10 WC Oncology SC Oncology GA 230WJ UT WOS:000325373700047 PM 23921646 ER PT J AU Luke, JJ Callahan, MK Postow, MA Romano, E Ramaiya, N Bluth, M Giobbie-Hurder, A Lawrence, DP Ibrahim, N Ott, PA Flaherty, KT Sullivan, RJ Harding, JJ D'Angelo, S Dickson, M Schwartz, GK Chapman, PB Wolchok, JD Hodi, FS Carvajal, RD AF Luke, Jason J. Callahan, Margaret K. Postow, Michael A. Romano, Emanuela Ramaiya, Nikhil Bluth, Mark Giobbie-Hurder, Anita Lawrence, Donald P. Ibrahim, Nageatte Ott, Patrick A. Flaherty, Keith T. Sullivan, Ryan J. Harding, James J. D'Angelo, Sandra Dickson, Mark Schwartz, Gary K. Chapman, Paul B. Wolchok, Jedd D. Hodi, F. Stephen Carvajal, Richard D. TI Clinical Activity of Ipilimumab for Metastatic Uveal Melanoma SO CANCER LA English DT Article DE uveal melanoma; ipilimumab; cytotoxic T-lymphocyteassociated protein 4; immunotherapy; absolute lymphocyte count ID OCULAR MELANOMA; IV MELANOMA; STAGE-III; SURVIVAL; EXPERIENCE; INTERLEUKIN-2; LYMPHOCYTE; EXPRESSION; TYROSINASE; MUTATIONS AB BACKGROUNDUveal melanoma exhibits a high incidence of metastases; and, to date, there is no systemic therapy that clearly improves outcomes. The anticytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab is a standard of care for metastatic melanoma; however, the clinical activity of CTLA-4 inhibition in patients with metastatic uveal melanoma is poorly defined. METHODSTo assess ipilimumab in this setting, the authors performed a multicenter, retrospective analysis of 4 hospitals in the United States and Europe. Clinical characteristics, toxicities, and radiographic disease burden, as determined by central, blinded radiology review, were evaluated. RESULTSThirty-nine patients with uveal melanoma were identified, including 34 patients who received 3 mg/kg ipilimumab and 5 who received 10 mg/kg ipilimumab. Immune-related response criteria and modified World Health Organization criteria were used to assess the response rate (RR) and the combined response plus stable disease (SD) rate after 12 weeks, after 23 weeks, and overall (median follow-up, 50.4 weeks [12.6 months]). At week 12, the RR was 2.6%, and the response plus SD rate was 46.%; at week 23, the RR was 2.6%, and the response plus SD rate was 28.2%. There was 1 complete response and 1 late partial response (at 100 weeks after initial SD) for an immune-related RR of 5.1%. Immune-related adverse events were observed in 28 patients (71.8%) and included 7 (17.9%) grade 3 and 4 events. Immune-related adverse events were more frequent in patients who received 10 mg/kg ipilimumab than in those who received 3 mg/kg ipilimumab. The median overall survival from the first dose of ipilimumab was 9.6 months (95% confidence interval, 6.3-13.4 months; range, 1.6-41.6 months). Performance status, lactate dehydrogenase level, and an absolute lymphocyte count 1000 cells/L at week 7 were associated significantly with survival. CONCLUSIONSIn this multicenter, retrospective analysis of 4 hospitals in the United States and Europe of patients with uveal melanoma, durable responses to ipilimumab and manageable toxicity were observed. Cancer 2013;119:3687-3695. (c) 2013 American Cancer Society. C1 [Luke, Jason J.; Ibrahim, Nageatte; Ott, Patrick A.; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Callahan, Margaret K.; Postow, Michael A.; Harding, James J.; D'Angelo, Sandra; Dickson, Mark; Schwartz, Gary K.; Chapman, Paul B.; Wolchok, Jedd D.; Carvajal, Richard D.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Romano, Emanuela] Univ Lausanne Hosp, Dept Oncol, Lausanne, Switzerland. [Ramaiya, Nikhil] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Bluth, Mark] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. [Giobbie-Hurder, Anita] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Lawrence, Donald P.; Flaherty, Keith T.; Sullivan, Ryan J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Carvajal, RD (reprint author), Mem Sloan Kettering Canc Ctr, Melanoma Sarcoma Serv, Dept Med, 300 East 66th St,BAIC 1071, New York, NY 10021 USA. EM carvajar@mskcc.org FU Bristol-Myers Squibb; GlaxcoSmithKline; Pfizer; MedImmune FX Dr. Callahan has acted as a paid consultant to Bristol-Myers Squibb and GlaxcoSmithKline and has received grant support from Bristol-Myers Squibb. Dr. Dickson has acted as paid consultant to Pfizer. Dr. Harding has acted as a paid consultant to MedImmune. Dr. Hodi has received clinical trial support and reimbursement for travel expenses from Bristol-Myers Squibb and has acted as a non-paid consultant to Bristol-Myers Squibb. Dr. Postow has received grants from Bristol-Myers Squibb and has received reimbursement for travel expenses from Bristol-Myers Squibb for investigator meetings related to immunotherapeutic agents, including ipilimumab. Dr. Wolchok has acted as a paid consultant to Bristol-Myers Squibb and has received reimbursement for travel/accommodations/meeting expenses and grant support from Bristol-Myers Squibb. NR 28 TC 51 Z9 51 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD OCT 15 PY 2013 VL 119 IS 20 BP 3687 EP 3695 DI 10.1002/cncr.28282 PG 9 WC Oncology SC Oncology GA 230WJ UT WOS:000325373700050 PM 23913718 ER PT J AU Wang, LL Suganuma, R Ikegaki, N Tang, X Naranjo, A McGrady, P London, WB Hogarty, MD Gastier-Foster, JM Look, AT Park, JR Maris, JM Cohn, SL Seeger, RC Shimada, H AF Wang, Larry L. Suganuma, Rie Ikegaki, Naohiko Tang, Xao Naranjo, Arlene McGrady, Patrick London, Wendy B. Hogarty, Michael D. Gastier-Foster, Julie M. Look, A. Thomas Park, Julie R. Maris, John M. Cohn, Susan L. Seeger, Robert C. Shimada, Hiroyuki TI Neuroblastoma of Undifferentiated Subtype, Prognostic Significance of Prominent Nucleolar Formation, and MYC/MYCN Protein Expression SO CANCER LA English DT Article DE neuroblastoma; undifferentiated subtype; MYCN amplification; MYC; MYCN expression; prognostic factors ID SCHWANNIAN STROMA-POOR; C-MYC PROTEIN; CHILDHOOD MEDULLOBLASTOMA; PATHOLOGY CLASSIFICATION; N-MYC; TUMORS; AMPLIFICATION; PROGRESSION; PHENOTYPE; COMMITTEE AB BACKGROUNDThis study sought to investigate biological/clinicopathological characteristics of neuroblastoma, undifferentiated subtype (NBUD). METHODSThis study examined 157 NBUD cases filed at the Children's Oncology Group Neuroblastoma Pathology Reference Laboratory, and survival rates of the patients were analyzed with known prognostic factors. Immunostainings for MYCN and MYC protein were performed on 68 tumors. RESULTSNBUD cases had a poor prognosis (48.4%5.0% 3-year event-free survival [EFS]; 56.5%5.0% overall survival [OS]), and were often associated with high mitosis-karyorrhexis index (MKI, 65%), prominent nucleoli (PN, 83%), 18 months of age (75%), MYCN amplification (MYCN-A, 83%), diploid pattern (63%), and 1pLOH (loss of heterozygosity (72%). However, these prognostic indicators, except for MYCN status, had no significant impact on survival. Surprisingly, EFS for patients with MYCN-A tumors (53.4%+/- 5.6%) was significantly better (P=.0248) than for patients with MYCN-nonamplified (MYCN-NA) tumors (31.7%+/- 11.7%), with MYCN-NA and PN (+) tumors having the worst prognosis (9.3%+/- 8.8%, P=.0045). Immunohistochemically, MYCN expression was found in 42 of 48 MYCN-A tumors. In contrast, MYC expression was almost exclusively found in the MYCN-NA tumors (9 of 20) especially when they had PN (8 of 11). Those patients with only MYC-positive tumors had the worst EFS (N=8, 12.5%+/- 11.7%) compared with only MYCN-positive (N=39, 49.9%+/- 17.7%) and both negative tumors (N=15, 70.0%+/- 17.1%) (P=.0029). High MKI was often found in only MYCN-positive (30 of 38) but rarely in only MYC-positive (2 of 8) tumors. CONCLUSIONSNBUD represents a unique subtype of neuroblastoma associated with a poor prognosis. In this subtype, MYC protein expression may be a new prognostic factor indicating more aggressive clinical behavior than MYCN amplification and subsequent MYCN protein expression. Cancer 2013;119:3718-3726. (c) 2013 American Cancer Society. Neuroblastoma, undifferentiated subtype, which is the histologically defined entity composed of neuroblasts often having prominent nucleoli, is frequently associated with poor prognostic factors. In this subtype, MYC protein expression could indicate more aggressive clinical behavior than MYCN amplification and subsequent MYCN protein expression. C1 [Wang, Larry L.; Suganuma, Rie; Shimada, Hiroyuki] Childrens Hosp Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90027 USA. [Wang, Larry L.; Suganuma, Rie; Seeger, Robert C.; Shimada, Hiroyuki] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Ikegaki, Naohiko; Tang, Xao] Univ Illinois, Coll Med, Dept Anat & Cell Biol, Chicago, IL USA. [Naranjo, Arlene; McGrady, Patrick] Univ Florida, Childrens Oncol Grp Stat & Data Ctr, Dept Biostat, Gainesville, FL USA. [London, Wendy B.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [London, Wendy B.] Boston Childrens Hosp, Childrens Oncol Grp Stat & Data Ctr, Boston, MA USA. [London, Wendy B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Hogarty, Michael D.] Univ Penn, Sch Med, Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Gastier-Foster, Julie M.] Ohio Univ, Coll Med, Nationwide Childrens Hosp, Dept Pathol & Lab Med, Columbus, OH USA. [Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Park, Julie R.] Univ Washington, Sch Med, Dept Pediat, Seattle Childrens Hosp, Seattle, WA 98195 USA. [Park, Julie R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Oncol, Philadelphia, PA 19104 USA. [Cohn, Susan L.] Univ Chicago, Dept Pediat, Div Hematol Oncol, Chicago, IL 60637 USA. [Seeger, Robert C.] Childrens Hosp Los Angeles, Div Hematol Oncol, Los Angeles, CA 90027 USA. RP Shimada, H (reprint author), Childrens Hosp Los Angeles, 4650 Sunset Blvd,MS 43, Los Angeles, CA 90027 USA. EM hshimada@chla.usc.edu FU NCI/SAIC; Children's Oncology Group; SWOG; NIH/NCI-Children's Oncology Group Statistics and Data Center; National Institutes of Health [U10 CA98413, U10 CA98543] FX Dr. Hogarty has received salary support for Children's Oncology Group (COG)-related activities, and travel to COG meetings has been reimbursed. He also has grants submitted and/or awarded for research from numerous granting agencies, received course instructor honorarium from Acadia University, has intellectual property on ARID1 (no patent filed, no monetary value anticipated), and is a committee member and is reimbursed for travel and honorarium from the American Board of Pediatrics. Dr. Gastier-Foster's institution has received, from NCI/SAIC, a contract to Biospecimen Core Resource for specimen processing, support from NCI/SAIC for travel to meetings for the study or other purposes, grants from NCI/SAIC, Children's Oncology Group, and SWOG, and travel/accommodations/meeting expenses from NCI, Children's Oncology Group, SWOG, American Board of Medical Genetics (unrelated to activities listed). Dr. London's institution has received grants from NIH/NCI-Children's Oncology Group Statistics and Data Center. Dr. Shimada has received National Institutes of Health grants U10 CA98413 and U10 CA98543. The other authors made no disclosure. NR 33 TC 12 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD OCT 15 PY 2013 VL 119 IS 20 BP 3718 EP 3726 DI 10.1002/cncr.28251 PG 9 WC Oncology SC Oncology GA 230WJ UT WOS:000325373700054 PM 23901000 ER PT J AU Dimitrov, SD Lu, D Naetar, N Hu, YD Pathania, S Kanellopoulou, C Livingston, DM AF Dimitrov, Stoil D. Lu, David Naetar, Nana Hu, Yiduo Pathania, Shailja Kanellopoulou, Chryssa Livingston, David M. TI Physiological modulation of endogenous BRCA1 p220 abundance suppresses DNA damage during the cell cycle SO GENES & DEVELOPMENT LA English DT Article DE BRCA1; miR-545; DNA damage; cell cycle; G0/G1 ID SPORADIC BREAST-CANCER; HOMOLOGOUS RECOMBINATION; TUMOR SUPPRESSION; GENE-EXPRESSION; OVARIAN-CANCER; MESSENGER-RNA; END RESECTION; NUCLEAR PHOSPHOPROTEIN; CHECKPOINT ACTIVATION; PROMOTER METHYLATION AB Endogenous BRCA1 p220 expression peaks in S and G2 when it is activated, and the protein participates in certain key DNA damage responses. In contrast, its expression is markedly reduced in G0/G1. While variations in transcription represent a significant part of p220 expression control, there is at least one other relevant process. We found that a microRNA, miR-545, that is expressed throughout the cell cycle down-modulates endogenous p220 mRNA and protein abundance directly in both G0/G1 and S/G2. When miR-545 function was inhibited by a specific antagomir, endogenous p220 expression increased in G0/G1, and aberrant p220-associated DNA damage responses and de novo DNA strand breaks accumulated. Analogous results were observed upon inhibition of miR-545 function in S/G2. Both sets of antagomir effects were mimicked by infecting cells with a p220 cDNA-encoding adenoviral vector. Thus, strand breaks were a product of p220 overexpression, and their prevention by miR-545 depends on its modulation of p220 expression. Breaks were also dependent on aberrant, overexpressed p220-driven recruitment of RAD51 to either spontaneously arising or mutagen-based DNA damage sites. Hence, when its level is not physiologically maintained, endogenous p220 aberrantly directs at least one DNA repair protein, RAD51, to damage sites, where their action contributes to the development of de novo DNA damage. Thus, like its loss, a surfeit of endogenous p220 function represents a threat to genome integrity. C1 [Dimitrov, Stoil D.; Lu, David; Naetar, Nana; Hu, Yiduo; Pathania, Shailja; Kanellopoulou, Chryssa; Livingston, David M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Dimitrov, Stoil D.; Lu, David; Naetar, Nana; Hu, Yiduo; Pathania, Shailja; Kanellopoulou, Chryssa; Livingston, David M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. RP Livingston, DM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM david_livingston@dfci.harvard.edu FU Breast Cancer SPORE grant; National Cancer Institute [5 P01CA80111]; Breast Cancer Research Foundation; Susan G. Komen Foundation for the Cure [SAC110022]; National Institutes of Health Training grant [5T32CA00938-30] FX We thank Ronny Drapkin, Daniel Silver, Jean Feunteun, Todd Golub, and members of the Livingston laboratory for insightful discussions and suggestions. We are grateful to Serena Landini for technical advice and help. We thank Asako Sakaue-Sawano and Atsushi Miyawaki (RIKEN) for the mAG1-hGem-expressing and mKO2-hCdt1-expressing vectors, and Dipanjan Chowdhury for graciously sharing results prior to publication. This work was supported by funds from the Breast Cancer SPORE grant to Dana-Farber/Harvard Cancer Center (to S.D.D. and D.M.L.) and grants from the National Cancer Institute (5 P01CA80111), the Breast Cancer Research Foundation, and the Susan G. Komen Foundation for the Cure (SAC110022) (to D.M.L.). Generous support for this work was also provided by the National Institutes of Health Training grant (5T32CA00938-30) (to S.D.D.). NR 89 TC 11 Z9 11 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD OCT 15 PY 2013 VL 27 IS 20 BP 2274 EP 2291 DI 10.1101/gad.225045.113 PG 18 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 238GP UT WOS:000325932500009 PM 24142877 ER PT J AU Shahian, DM Jacobs, JP Edwards, FH Brennan, JM Dokholyan, RS Prager, RL Wright, CD Peterson, ED McDonald, DE Grover, FL AF Shahian, David M. Jacobs, Jeffrey P. Edwards, Fred H. Brennan, J. Matthew Dokholyan, Rachel S. Prager, Richard L. Wright, Cameron D. Peterson, Eric D. McDonald, Donna E. Grover, Frederick L. TI The Society of Thoracic Surgeons National Database SO HEART LA English DT Article ID ADULT CARDIAC-SURGERY; CONGENITAL HEART-SURGERY; BYPASS-GRAFTING SURGERY; PERCUTANEOUS CORONARY INTERVENTION; RISK-ADJUSTMENT MODEL; LONG-TERM SURVIVAL; STS DATABASE; LUNG-CANCER; REVASCULARIZATION STRATEGIES; ADMINISTRATIVE DATABASES AB Aims The Society of Thoracic Surgeons (STS) National Database collects detailed clinical information on patients undergoing adult cardiac, paediatric and congenital cardiac, and general thoracic surgical operations. These data are used to support risk-adjusted, nationally benchmarked performance assessment and feedback; voluntary public reporting; quality improvement initiatives; guideline development; appropriateness determination; shared decision making; research using cross-sectional and longitudinal registry linkages; comparative effectiveness studies; government collaborations including postmarket surveillance; regulatory compliance and reimbursement strategies. Interventions All database participants receive feedback reports which they may voluntarily share with their hospitals or payers, or publicly report. STS analyses are regularly used as the basis for local, regional and national quality improvement efforts. Population More than 90% of adult cardiac programmes in the USA participate, as do the majority of paediatric cardiac programmes, and general thoracic participation continues to increase. Since the inception of the Database in 1989, more than 5 million patient records have been submitted. Baseline data Each of the three subspecialty databases includes several hundred variables that characterise patient demographics, diagnosis, medical history, clinical risk factors and urgency of presentation, operative details and postoperative course including adverse outcomes. Data capture Data are entered by trained data abstractors and by the care team, using detailed data specifications for each element. Data quality Quality and consistency checks assure accurate and complete data, missing data are rare, and audits are performed annually of selected participant sites. Endpoints All major outcomes are reported including complications, status at discharge and mortality. Data access Applications for STS Database participants to use aggregate national data for research are available at http://www.sts.org/quality-research-patient-safety/research/publications-and-research/access-data-sts-national-database. C1 [Shahian, David M.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Shahian, David M.] Harvard Univ, Sch Med, Ctr Qual & Safety, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Jacobs, Jeffrey P.] Univ S Florida, All Childrens Hosp, Johns Hopkins Childrens Heart Surg, St Petersburg, FL 33701 USA. [Jacobs, Jeffrey P.] All Childrens Hosp, Johns Hopkins Childrens Heart Surg, Tampa, FL USA. [Jacobs, Jeffrey P.] All Childrens Hosp, Johns Hopkins Childrens Heart Surg, Orlando, FL USA. [Jacobs, Jeffrey P.] Florida Hosp Children, St Petersburg, FL USA. [Jacobs, Jeffrey P.] Florida Hosp Children, Tampa, FL USA. [Jacobs, Jeffrey P.] Florida Hosp Children, Orlando, FL USA. [Edwards, Fred H.] Univ Florida Coll Med Jacksonville, Shands Jacksonville, Jacksonville, FL USA. [Brennan, J. Matthew; Dokholyan, Rachel S.; Peterson, Eric D.] Duke Univ Med Ctr, DCRI, Durham, NC USA. [Prager, Richard L.] Univ Michigan Hlth Syst, Dept Cardiac Surg, Ann Arbor, MI USA. [Wright, Cameron D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Surg, Boston, MA USA. [McDonald, Donna E.] Soc Thorac Surg, Chicago, IL USA. [Grover, Frederick L.] Univ Colorado Denver, Sch Med, Dept Surg, Aurora, CO USA. RP Shahian, DM (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org NR 69 TC 43 Z9 45 U1 0 U2 10 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 EI 1468-201X J9 HEART JI Heart PD OCT 15 PY 2013 VL 99 IS 20 BP 1494 EP 1501 DI 10.1136/heartjnl-2012-303456 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 221FV UT WOS:000324644200006 PM 23335498 ER PT J AU Brandauer, J Vienberg, SG Andersen, MA Ringholm, S Risis, S Larsen, PS Kristensen, JM Frosig, C Leick, L Fentz, J Jorgensen, S Kiens, B Wojtaszewski, JFP Richter, EA Zierath, JR Goodyear, LJ Pilegaard, H Treebak, JT AF Brandauer, Josef Vienberg, Sara G. Andersen, Marianne A. Ringholm, Stine Risis, Steve Larsen, Per S. Kristensen, Jonas M. Frosig, Christian Leick, Lotte Fentz, Joachim Jorgensen, Sebastian Kiens, Bente Wojtaszewski, Jorgen F. P. Richter, Erik A. Zierath, Juleen R. Goodyear, Laurie J. Pilegaard, Henriette Treebak, Jonas T. TI AMP-activated protein kinase regulates nicotinamide phosphoribosyl transferase expression in skeletal muscle SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID CALORIE RESTRICTION; SACCHAROMYCES-CEREVISIAE; GLUCOSE-HOMEOSTASIS; INSULIN SENSITIVITY; LIFE-SPAN; SIRT1; PGC-1-ALPHA; METABOLISM; EXERCISE; METFORMIN AB Deacetylases such as sirtuins (SIRTs) convert NAD to nicotinamide (NAM). Nicotinamide phosphoribosyl transferase (Nampt) is the rate-limiting enzyme in the NAD salvage pathway responsible for converting NAM to NAD to maintain cellular redox state. Activation of AMP-activated protein kinase (AMPK) increases SIRT activity by elevating NAD levels. As NAM directly inhibits SIRTs, increased Nampt activation or expression could be a metabolic stress response. Evidence suggests that AMPK regulates Nampt mRNA content, but whether repeated AMPK activation is necessary for increasing Nampt protein levels is unknown. To this end, we assessed whether exercise training- or 5-amino-1--d-ribofuranosyl-imidazole-4-carboxamide (AICAR)-mediated increases in skeletal muscle Nampt abundance are AMPK dependent. One-legged knee-extensor exercise training in humans increased Nampt protein by 16% (P < 0.05) in the trained, but not the untrained leg. Moreover, increases in Nampt mRNA following acute exercise or AICAR treatment (P < 0.05 for both) were maintained in mouse skeletal muscle lacking a functional AMPK 2 subunit. Nampt protein was reduced in skeletal muscle of sedentary AMPK 2 kinase dead (KD), but 6.5 weeks of endurance exercise training increased skeletal muscle Nampt protein to a similar extent in both wild-type (WT) (24%) and AMPK 2 KD (18%) mice. In contrast, 4 weeks of daily AICAR treatment increased Nampt protein in skeletal muscle in WT mice (27%), but this effect did not occur in AMPK 2 KD mice. In conclusion, functional 2-containing AMPK heterotrimers are required for elevation of skeletal muscle Nampt protein, but not mRNA induction. These findings suggest AMPK plays a post-translational role in the regulation of skeletal muscle Nampt protein abundance, and further indicate that the regulation of cellular energy charge and nutrient sensing is mechanistically related. C1 [Brandauer, Josef; Vienberg, Sara G.; Andersen, Marianne A.; Risis, Steve; Larsen, Per S.; Zierath, Juleen R.; Treebak, Jonas T.] Univ Copenhagen, Novo Nordisk Fdn, Ctr Basic Metab Res, Sect Integrat Physiol, DK-2200 Copenhagen, Denmark. [Brandauer, Josef] Gettysburg Coll, Dept Hlth Sci, Gettysburg, PA 17325 USA. [Brandauer, Josef; Goodyear, Laurie J.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Metab Sect, Boston, MA 02115 USA. [Ringholm, Stine; Leick, Lotte; Pilegaard, Henriette] Univ Copenhagen, August Krogh Ctr, Dept Biol, DK-2200 Copenhagen, Denmark. [Kristensen, Jonas M.; Frosig, Christian; Fentz, Joachim; Jorgensen, Sebastian; Kiens, Bente; Wojtaszewski, Jorgen F. P.; Richter, Erik A.] Univ Copenhagen, August Krogh Ctr, Dept Nutr Exercise & Sports, Sect Mol Physiol, DK-2200 Copenhagen, Denmark. [Zierath, Juleen R.] Karolinska Inst, Dept Mol Med, Sect Integrat Physiol, Stockholm, Sweden. [Zierath, Juleen R.] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden. RP Treebak, JT (reprint author), Univ Copenhagen, NNF Ctr Basic Metab Res, Blegdamsvej 3B,6-6-28, DK-2200 Copenhagen, Denmark. EM jttreebak@sund.ku.dk RI Pilegaard, Henriette/M-2315-2014; Wojtaszewski, Jorgen /P-6583-2014; Frosig, Christian/A-3750-2015; Fentz, Joachim/B-1973-2015; Treebak, Jonas/B-4521-2017; OI Pilegaard, Henriette/0000-0002-1071-0327; Wojtaszewski, Jorgen /0000-0001-9785-6830; Frosig, Christian/0000-0001-9302-9328; Fentz, Joachim/0000-0002-9334-1298; Treebak, Jonas/0000-0003-1488-7012; Agerholm Andersen, Marianne/0000-0001-8687-1031; Zierath, Juleen/0000-0001-6891-7497 FU Novo Nordisk Foundation Center for Basic Metabolic Research; Novo Nordisk Foundation; Danish Agency for Science, Technology and Innovation; Gettysburg College; Danish National Research Foundation [504-14, 02-512-555]; Research and Technological Development Projects [QLG1-CT-2001-01488]; European Commission; Media and Grants Secretariat of the Danish Ministry of Culture; Danish Diabetes Association; Danish Medical Research Council; Lundbeck Foundation; European Commission FP6 Integrated Project Exgenesis [LSHM-CT-2004-005272]; Danish Natural Science Research Council FX Support for this project was provided by the Novo Nordisk Foundation Center for Basic Metabolic Research and the Novo Nordisk Foundation to Jonas T. Treebak. Jonas T. Treebak was supported by a postdoctoral fellowship from The Danish Agency for Science, Technology and Innovation. Josef Brandauer was supported by a Research and Professional Development Grant by Gettysburg College. J. F. P. Wojtaszewski was supported by a Hallas Moller fellowship from the Novo Nordisk Foundation.; The human training study was supported by grants from the Danish National Research Foundation (no. 504-14), a Research and Technological Development Projects (QLG1-CT-2001-01488) grant funded by the European Commission, by the Media and Grants Secretariat of the Danish Ministry of Culture, by the Danish Diabetes Association, by the Novo Nordisk Foundation, and by the Danish Medical Research Council.; Experiments in PGC-1 alpha KO mice were supported by the Lundbeck Foundation, the Novo Nordisk Foundation and a grant from the European Commission FP6 Integrated Project Exgenesis (Ref. LSHM-CT-2004-005272). Support was also provided by the Danish National Research Foundation (grant no. 02-512-555) to the Centre of Inflammation and Metabolism.; Studies in AMPK alpha 2 KO mice were funded by the Danish National Research Foundation (#504-14), the Danish Diabetes Association, the Danish Medical Research Council, the Danish Natural Science Research Council, the Novo Nordisk Foundation and by an integrated project (contract LSHM-CT-2004-005272) funded by the European Commission. NR 53 TC 22 Z9 22 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 EI 1469-7793 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD OCT 15 PY 2013 VL 591 IS 20 BP 5207 EP 5220 DI 10.1113/jphysiol.2013.259515 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 238VX UT WOS:000325980700027 PM 23918774 ER PT J AU Wills, LP Beeson, GC Trager, RE Lindsey, CC Beeson, CC Peterson, YK Schnellmann, RG AF Wills, Lauren P. Beeson, Gyda C. Trager, Richard E. Lindsey, Christopher C. Beeson, Craig C. Peterson, Yuri K. Schnellmann, Rick G. TI High-throughput respirometric assay identifies predictive toxicophore of mitochondrial injury SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Mitochondria; Toxicophore; Renal proximal tubule cells; LOPAC; ChemBridge; Seahorse Biosciences Extracellular Flux ID OXYGEN-SENSITIVE PROBES; IN-VITRO; PERMEABILITY TRANSITION; TOXICITY; CELLS; DRUGS; MECHANISMS; APOPTOSIS; CULTURE; TARGETS AB Many environmental chemicals and drugs negatively affect human health through deleterious effects on mitochondrial function. Currently there is no chemical library of mitochondrial toxicants, and no reliable methods for predicting mitochondrial toxicity. We hypothesized that discrete toxicophores defined by distinct chemical entities can identify previously unidentified mitochondrial toxicants. We used a respirometric assay to screen 1760 compounds (5 mu M) from the LOPAC and ChemBridge DIVERSet libraries. Thirty-one of the assayed compounds decreased uncoupled respiration, a stress test for mitochondrial dysfunction, prior to a decrease in cell viability and reduced the oxygen consumption rate in isolated mitochondria. The mitochondrial toxicants were grouped by chemical similarity and two clusters containing four compounds each were identified. Cheminformatic analysis of one of the clusters identified previously uncharacterized mitochondrial toxicants from the ChemBridge DIVERSet This approach will enable the identification of mitochondrial toxicants and advance the prediction of mitochondrial toxicity for both drug discovery and risk assessment. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved. C1 [Beeson, Gyda C.; Trager, Richard E.; Lindsey, Christopher C.; Peterson, Yuri K.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. [Wills, Lauren P.; Beeson, Craig C.] MitoHealth Inc, Charleston, SC 29403 USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM schnell@musc.edu FU NCRR NIH HHS [S10 RR027122]; NIEHS NIH HHS [R43 ES019378, R44 ES019378]; NIGMS NIH HHS [R01 GM084147, R43 GM097770] NR 44 TC 5 Z9 5 U1 1 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD OCT 15 PY 2013 VL 272 IS 2 BP 490 EP 502 DI 10.1016/j.taap.2013.06.014 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 237XS UT WOS:000325905500025 PM 23811330 ER PT J AU Chavarro, JE Kenfield, SA Stampfer, MJ Loda, M Campos, H Sesso, HD Ma, J AF Chavarro, Jorge E. Kenfield, Stacey A. Stampfer, Meir J. Loda, Massimo Campos, Hannia Sesso, Howard D. Ma, Jing TI Blood Levels of Saturated and Monounsaturated Fatty Acids as Markers of De Novo Lipogenesis and Risk of Prostate Cancer SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE biomarkers; epidemiology; fatty acids; nutrition; prostate cancer ID C-REACTIVE PROTEIN; BODY-MASS INDEX; ADIPOSE-TISSUE; WHOLE-BLOOD; PLASMA; SYNTHASE; INHIBITION; APOPTOSIS; CELLS; EXPRESSION AB De novo lipogenesis has been implicated in prostate carcinogenesis, and blood levels of specific saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) could reflect activity of this pathway. We used gas chromatography to measure blood SFA and MUFA levels in prediagnostic samples from 476 incident prostate cancer cases (19821995) in the Physicians Health Study and an equal number of controls matched on age and smoking status. Five tagging polymorphisms in the fatty acid synthase (FASN) gene (rs1127678, rs6502051, rs4246444, rs12949488, and rs8066956) were related to blood SFA and MUFA levels. Conditional logistic regression was used to estimate the rate ratios, with 95 confidence intervals, of prostate cancer across quintiles of blood fatty acid levels. The polymorphisms rs6502051 and rs4246444 were associated with lower levels of 14:1n-5, 16:1n-7, and 18:1n-9. Blood levels of 16:1n-7 were associated with higher prostate cancer incidence, with rate ratios for men in increasing quintiles of 1.00, 1.40, 1.35, 1.44, and 1.97 (95 confidence interval: 1.273.06; P-trend 0.003). Furthermore, 16:1n-7 levels were positively related to incidence of high-grade (Gleason score 7) tumors (rate ratio(Q5Q1) 3.92; 95 confidence interval: 1.728.94) but not low-grade tumors (rate ratio(Q5Q1) 1.51; 95 confidence interval: 0.872.62) (P-heterogeneity 0.02). Higher activity of enzymes involved in de novo lipogenesis, as reflected in blood levels of 16:1n-7, could be involved in the development of high-grade prostate cancer. C1 [Chavarro, Jorge E.; Stampfer, Meir J.; Campos, Hannia] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chavarro, Jorge E.; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chavarro, Jorge E.; Stampfer, Meir J.; Ma, Jing] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Div Network Med,Dept Med, Boston, MA 02115 USA. [Kenfield, Stacey A.] Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94143 USA. [Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sesso, Howard D.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med,Dept Med, Boston, MA 02115 USA. RP Chavarro, JE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM jchavarr@hsph.harvard.edu FU US Department of Defense [W81XWH-11-1-0529]; National Institutes of Health [CA42182, CA58684, CA90598, CA141298, CA97193, CA34944, CA40360, CA131945, P50CA90381, 1U54CA155626-01, P30DK046200, HL26490, HL34595] FX This work was supported by grant W81XWH-11-1-0529 from the US Department of Defense and grants CA42182, CA58684, CA90598, CA141298, CA97193, CA34944, CA40360, CA131945, P50CA90381, 1U54CA155626-01, P30DK046200, HL26490, and HL34595 from the National Institutes of Health. NR 39 TC 9 Z9 9 U1 0 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 15 PY 2013 VL 178 IS 8 BP 1246 EP 1255 DI 10.1093/aje/kwt136 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 235YK UT WOS:000325759000010 PM 23989197 ER PT J AU Reginato, E Mroz, P Chung, H Kawakubo, M Wolf, P Hamblin, MR AF Reginato, E. Mroz, P. Chung, H. Kawakubo, M. Wolf, P. Hamblin, M. R. TI Photodynamic therapy plus regulatory T-cell depletion produces immunity against a mouse tumour that expresses a self-antigen SO BRITISH JOURNAL OF CANCER LA English DT Article DE photodynamic therapy; regulatory T cells; TGF beta; CT26 tumour; anti-tumour immunity ID LOW-DOSE CYCLOPHOSPHAMIDE; GROWTH-FACTOR-BETA; TGF-BETA; ANTITUMOR IMMUNITY; MURINE TUMOR; HUMAN CANCER; INDUCTION; IMMUNOTHERAPY; AUTOIMMUNITY; LYMPHOCYTES AB Background: Photodynamic therapy (PDT) can lead to development of antigen-specific immune response and PDT-mediated immunity can be potentiated by T regulatory cell (Treg) depletion. We investigated whether the combination of PDT with cyclophosphamide (CY) could foster immunity against wild-type tumours expressing self-antigen (gp70). Methods: Mice with CT26 tumours were treated with PDT alone or in combination with low-dose CY. T regulatory cell numbers and transforming growth factor-beta (TGF-beta) levels were measured at several time points after treatment. Mice cured by PDT+CY were rechallenged with CT26 and monitored for long-term survival. Results: Photodynamic therapy+CY led to complete tumour regression and long-term survival in 90% of treated mice while the absolute numbers of Treg decreased after PDT+CY and the TGF-beta levels were reduced to a level comparable to naive mice. Sixty-five percent of the mice treated with PDT+CY that survived over 90 days tumour free rejected the rechallenge with the same tumour when a second dose of CY was administered before rechallenge but not without. Conclusion: Administration of CY before PDT led to depletion of Treg and potentiated PDT-mediated immunity, leading to long-term survival and development of memory immunity that was only uncovered by second Treg depletion. C1 [Reginato, E.; Mroz, P.; Chung, H.; Kawakubo, M.; Hamblin, M. R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Reginato, E.; Wolf, P.] Med Univ Graz, Dept Dermatol, A-8036 Graz, Austria. [Mroz, P.; Chung, H.; Hamblin, M. R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Mroz, P.] Northwestern Univ, Dept Pathol, Chicago, IL 60611 USA. [Hamblin, M. R.] Harvard Mit Div Hlth Sci & Technol, Boston, 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 [AI050875]; Medical University of Graz, Graz, Austria FX Research in the Hamblin laboratory is supported by US NIH grant AI050875. ER was supported by the PhD program of the Medical University of Graz, Graz, Austria. NR 47 TC 17 Z9 18 U1 2 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD OCT 15 PY 2013 VL 109 IS 8 BP 2167 EP 2174 DI 10.1038/bjc.2013.580 PG 8 WC Oncology SC Oncology GA 236KN UT WOS:000325795000017 PM 24064977 ER PT J AU Jorgenson, TC Zhong, WX Oberley, TD AF Jorgenson, Tonia C. Zhong, Weixiong Oberley, Terry D. TI Redox Imbalance and Biochemical Changes in Cancer SO CANCER RESEARCH LA English DT Article ID MOLECULAR-MECHANISMS; S-GLUTATHIONYLATION; OXIDATIVE STRESS; THIOREDOXIN; ACTIVATION; CELLS; NRF2; SUMOYLATION; METHYLATION; LEUKEMIA AB For this article, we explore a hypothesis involving the possible role of reduction/oxidation (redox) state in cancer. We hypothesize that many modifications in cellular macromolecules, observed in cancer progression, may be caused by redox imbalance. Recent biochemical data suggest that human prostate cancer cell lines show a redox imbalance (oxidizing) compared with benign primary prostate epithelial cells; the degree of oxidation varied with aggressive behavior of each cell line. Our recent data suggest that human breast cancer tissues show a redox imbalance (reducing) compared with benign adjacent breast tissues. Accumulating data summarized in this article suggest that redox imbalance may regulate gene expression and alter protein stability by posttranslational modifications, in turn modulating existing cellular programs. Despite significant improvements in cancer therapeutics, resistance occurs, and redox imbalance may play a role in this process. Studies show that some cancer therapeutic agents increase generation of reactive oxygen/nitrogen species and antioxidant enzymes, which may alter total antioxidant capacity, cause cellular adaptation, and result in reduced effectiveness of treatment modalities. Approaches involving modulations of intra-and extracellular redox states, in combination with other therapies, may lead to new treatment options, especially for patients who are resistant to standard treatments. Cancer Res; 73(20); 6118-23. (C) 2013 AACR. C1 [Jorgenson, Tonia C.; Zhong, Weixiong; Oberley, Terry D.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Inst Med Res, Dept Pathol & Lab Med, Madison, WI 53705 USA. [Zhong, Weixiong; Oberley, Terry D.] William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Madison, WI 53705 USA. RP Jorgenson, TC (reprint author), Univ Wisconsin, Wisconsin Inst Med Res, 1111 Highland Ave, Madison, WI 53705 USA. EM tjorgenson@wisc.edu FU Department of Pathology and Laboratory Medicine, University of Wisconsin; NCI UW Carbone Comprehensive Cancer Center (NIH) [P30 CA014520]; NIH [RO1CA139844, RO1CA139843, RO1CA073599] FX This work was supported in part by funds from the Department of Pathology and Laboratory Medicine, University of Wisconsin, NCI UW Carbone Comprehensive Cancer Center (NIH grant P30 CA014520), NIH grants RO1CA139844, RO1CA139843, RO1CA073599 (TDO-CoI), and resources and facilities at the William S. Middleton Memorial Veterans Hospital (Madison, WI). Tonia C. Jorgenson is supported in part by PF-13-286-01-TBE from the American Cancer Society. NR 30 TC 26 Z9 27 U1 0 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 2013 VL 73 IS 20 BP 6118 EP 6123 DI 10.1158/0008-5472.CAN-13-1117 PG 6 WC Oncology SC Oncology GA 236KV UT WOS:000325796100004 PM 23878188 ER PT J AU Kaelin, W Livingston, D Loda, M Vousden, K Mihich, E AF Kaelin, William Livingston, David Loda, Massimo Vousden, Karen Mihich, Enrico TI Twenty-fifth Annual Pezcoller Symposium: Metabolism and Tumorigenesis SO CANCER RESEARCH LA English DT Editorial Material ID DIFFERENTIATION; PROMOTE; GROWTH; CELLS AB Choking cancer via inhibition of metabolic enzymes essential for tumor but dispensable in normal tissues was discussed as was the altered metabolism in cancer cells related to: tumor suppressor protein (pVHL) function, the histone acetylation dependence upon glucose, the epigenomic reprogramming of acetyl CoA synthesis, the plasticity of aging mechanisms, and the metabolism orchestration in macrophage polarization. The p53 and p73 pathways role in metabolic adaptation, the effects on growth of AMP-dependent kinase, the growth regulation by the mTOR pathways, and the bioenergetics requirements of cancer cells were also discussed. A novel computational model of personalized metabolic changes in cancer was outlined with applications in patients with breast cancer. Imaging metabolic characteristics of tumors by MRI and C-13-nuclear magnetic resonance was described. The cancer metabolism regulation related to O-linked beta-N-acetylglucosame was described. DNA hypermethylation and impaired hematopoietic differentiation in AML after isocitrate dehydrogenase 1/2 mutation and 2-hydroxyglutarate increases were outlined. Cancer Res; 73(20); 6124-7. (C) 2013 AACR. C1 [Kaelin, William; Livingston, David; Loda, Massimo; Mihich, Enrico] Dana Farber Canc Inst, Boston, MA 02115 USA. [Loda, Massimo] Harvard Univ, Sch Med, Boston, MA USA. [Vousden, Karen] Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland. RP Mihich, E (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM enrico_mihich@dfci.harvard.edu NR 14 TC 0 Z9 0 U1 1 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 2013 VL 73 IS 20 BP 6124 EP 6127 DI 10.1158/0008-5472.CAN-13-2445 PG 4 WC Oncology SC Oncology GA 236KV UT WOS:000325796100005 PM 24097824 ER PT J AU Pfaffle, HN Wang, M Gheorghiu, L Ferraiolo, N Greninger, P Borgmann, K Settleman, J Benes, CH Sequist, LV Zou, L Willers, H AF Pfaeffle, Heike N. Wang, Meng Gheorghiu, Liliana Ferraiolo, Natalie Greninger, Patricia Borgmann, Kerstin Settleman, Jeffrey Benes, Cyril H. Sequist, Lecia V. Zou, Lee Willers, Henning TI EGFR-Activating Mutations Correlate with a Fanconi Anemia-like Cellular Phenotype That Includes PARP Inhibitor Sensitivity SO CANCER RESEARCH LA English DT Article ID CROSS-LINK REPAIR; GROWTH-FACTOR RECEPTOR; HOMOLOGOUS RECOMBINATION REPAIR; DOUBLE-STRAND BREAKS; DNA-REPAIR; LUNG-CANCER; POLY(ADP-RIBOSE) POLYMERASE; IONIZING-RADIATION; TUMOR-CELLS; NSCLC CELLS AB In patients with lung cancer whose tumors harbor activating mutations in the EGF receptor (EGFR), increased responses to platinum-based chemotherapies are seen compared with wild-type cancers. However, the mechanisms underlying this association have remained elusive. Here, we describe a cellular phenotype of cross-linker sensitivity in a subset of EGFR-mutant lung cancer cell lines that is reminiscent of the defects seen in cells impaired in the Fanconi anemia pathway, including a pronounced G(2)-M cell-cycle arrest and chromosomal radial formation. We identified a defect downstream of FANCD2 at the level of recruitment of FAN1 nuclease and DNA interstrand cross-link (ICL) unhooking. The effect of EGFR mutation was epistatic with FANCD2. Consistent with the known role of FANCD2 in promoting RAD51 foci formation and homologous recombination repair (HRR), EGFR-mutant cells also exhibited an impaired RAD51 foci response to ICLs, but not to DNA double-strand breaks. EGFR kinase inhibition affected RAD51 foci formation neither in EGFR-mutant nor wild-type cells. In contrast, EGFR depletion or overexpression of mutant EGFR in wild-type cells suppressed RAD51 foci, suggesting an EGFR kinase-independent regulation of DNA repair. Interestingly, EGFR-mutant cells treated with the PARP inhibitor olaparib also displayed decreased FAN1 foci induction, coupled with a putative block in a late HRR step. As a result, EGFR-mutant lung cancer cells exhibited olaparib sensitivity in vitro and in vivo. Our findings provide insight into the mechanisms of cisplatin and PARP inhibitor sensitivity of EGFR-mutant cells, yielding potential therapeutic opportunities for further treatment individualization in this genetically defined subset of lung cancer. Cancer Res; 73(20); 6254-63. (C) 2013 AACR. C1 [Pfaeffle, Heike N.; Wang, Meng; Gheorghiu, Liliana; Ferraiolo, Natalie; Willers, Henning] Harvard Univ, Lab Cellular & Mol Radiat Oncol, Dept Radiat Oncol, Sch Med,Massachusetts Gen Hosp, Charlestown, MA USA. [Sequist, Lecia V.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Greninger, Patricia; Settleman, Jeffrey; Benes, Cyril H.; Zou, Lee] Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Res, Charlestown, MA USA. [Settleman, Jeffrey] Genentech Inc, Res Oncol, San Francisco, CA 94080 USA. [Pfaeffle, Heike N.] Univ Munich, Dept Pharmaceut Biol, Munich, Germany. [Borgmann, Kerstin] Univ Hamburg, Ctr Oncol, Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany. RP Willers, H (reprint author), Massachusetts Gen Hosp, Cox 3,55 Fruit St, Boston, MA 02114 USA. EM hwillers@partners.org FU Dana-Farber/Harvard Cancer Center SPORE in Lung Cancer, NCI [P50 CA090578]; Department of Defense [W81XWH-06-1-0309]; UK Wellcome Trust [086357]; Massachusetts General Hospital, Proton Therapy Research and Treatment Center [C06 CA059267] FX This work was supported by the Dana-Farber/Harvard Cancer Center SPORE in Lung Cancer, NCI P50 CA090578 (J. Settleman, L. Zou, and H. Willers), Department of Defense W81XWH-06-1-0309 (H. Willers), the UK Wellcome Trust 086357 (C.H. Benes and J. Settleman), and the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center (L. Zou, L.V. Sequist, and H. Willers). NR 49 TC 11 Z9 11 U1 2 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 2013 VL 73 IS 20 BP 6254 EP 6263 DI 10.1158/0008-5472.CAN-13-0044 PG 10 WC Oncology SC Oncology GA 236KV UT WOS:000325796100017 PM 23966292 ER PT J AU Abazeed, ME Adams, DJ Hurov, KE Tamayo, P Creighton, CJ Sonkin, D Giacomelli, AO Du, C Fries, DF Wong, KK Mesirov, JP Loeffler, JS Schreiber, SL Hammerman, PS Meyerson, M AF Abazeed, Mohamed E. Adams, Drew J. Hurov, Kristen E. Tamayo, Pablo Creighton, Chad J. Sonkin, Dmitriy Giacomelli, Andrew O. Du, Charles Fries, Daniel F. Wong, Kwok-Kin Mesirov, Jill P. Loeffler, Jay S. Schreiber, Stuart L. Hammerman, Peter S. Meyerson, Matthew TI Integrative Radiogenomic Profiling of Squamous Cell Lung Cancer SO CANCER RESEARCH LA English DT Article ID ANTIOXIDANT RESPONSE ELEMENTS; GENE-EXPRESSION; RADIATION SENSITIVITY; CONNECTIVITY MAP; NRF2; CARCINOMA; KINASE; P53; RESISTANCE; INHIBITORS AB Radiotherapy is one of the mainstays of anticancer treatment, but the relationship between the radiosensitivity of cancer cells and their genomic characteristics is still not well defined. Here, we report the development of a high-throughput platform for measuring radiation survival in vitro and its validation in comparison with conventional clonogenic radiation survival analysis. We combined results from this high-throughput assay with genomic parameters in cell lines from squamous cell lung carcinoma, which is standardly treated by radiotherapy, to identify parameters that predict radiation sensitivity. We showed that activation of NFE2L2, a frequent event in lung squamous cancers, confers radiation resistance. An expression-based, in silico screen nominated inhibitors of phosphoinositide 3-kinase (PI3K) as NFE2L2 antagonists. We showed that the selective PI3K inhibitor, NVP-BKM120, both decreased NRF2 protein levels and sensitized NFE2L2 or KEAP1-mutant cells to radiation. We then combined results from this high-throughput assay with single-sample gene set enrichment analysis of gene expression data. The resulting analysis identified pathways implicated in cell survival, genotoxic stress, detoxification, and innate and adaptive immunity as key correlates of radiation sensitivity. The integrative and high-throughput methods shown here for large-scale profiling of radiation survival and genomic features of solid-tumor-derived cell lines should facilitate tumor radiogenomics and the discovery of genotype-selective radiation sensitizers and protective agents. Cancer Res; 73(20); 6289-98. (C) 2013 AACR. C1 [Abazeed, Mohamed E.] Harvard Univ, Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Giacomelli, Andrew O.] Harvard Univ, Div Med Sci, Boston, MA 02115 USA. [Loeffler, Jay S.] Harvard Univ, Sch Med, Dept Radiat Therapy, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Fries, Daniel F.; Wong, Kwok-Kin; Hammerman, Peter S.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Wong, Kwok-Kin] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA. [Meyerson, Matthew] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Adams, Drew J.; Schreiber, Stuart L.] Chem Biol Program, Cambridge, MA USA. [Schreiber, Stuart L.] Howard Hughes Med Inst, Cambridge, MA USA. [Adams, Drew J.; Tamayo, Pablo; Mesirov, Jill P.; Schreiber, Stuart L.; Hammerman, Peter S.; Meyerson, Matthew] Broad Inst MIT & Harvard, Cambridge, MA USA. [Hurov, Kristen E.; Sonkin, Dmitriy] Novartis Inst Biomed Res, Cambridge, MA USA. [Schreiber, Stuart L.] Dept Chem & Chem Biol, Cambridge, MA USA. [Du, Charles; Schreiber, Stuart L.] Harvard Univ, Cambridge, MA 02138 USA. [Creighton, Chad J.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dana Bldg,Room 1540,44 Binney St,1523A, Boston, MA 02215 USA. EM phammerman@partners.org; matthew_meyerson@dfci.harvard.edu OI Sonkin, Dmitriy/0000-0002-1649-0652; wong, kwok kin/0000-0001-6323-235X FU NIH [5T32CA009382-30, RC2 CA138399-01]; Harvard Radiation Oncology Program; NCI [RO1 CA109038]; Stephen D. and Alice Cutler Investigator Fund; National Institute of General Medical Sciences [GM38627]; [K08 CA163677] FX M.E. Abazeed was supported by NIH training grant 5T32CA009382-30 and by funding from the Harvard Radiation Oncology Program. M. Meyerson was supported by NCI RO1 CA109038. P.S. Hammerman was supported by the Stephen D. and Alice Cutler Investigator Fund and by K08 CA163677. The experiments described in Supplementary Fig. S3 were supported in part by NIH RC2 CA138399-01 (S.L. Schreiber). National Institute of General Medical Sciences provided partial support (GM38627; S.L. Schreiber). NR 50 TC 27 Z9 28 U1 1 U2 15 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 2013 VL 73 IS 20 BP 6289 EP 6298 DI 10.1158/0008-5472.CAN-13-1616 PG 10 WC Oncology SC Oncology GA 236KV UT WOS:000325796100020 PM 23980093 ER PT J AU Hyder, JA Barbara, DW AF Hyder, Joseph A. Barbara, David W. TI Letter by Hyder and Barbara Regarding Article, "Perioperative Dexmedetomidine Improves Outcomes of Cardiac Surgery" SO CIRCULATION LA English DT Letter C1 [Hyder, Joseph A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. [Barbara, David W.] Mayo Clin, Coll Med, Dept Anesthesiol, Rochester, MN USA. RP Hyder, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 2 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 OCT 15 PY 2013 VL 128 IS 16 BP E336 EP E336 DI 10.1161/CIRCULATIONAHA.113.003733 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 235AP UT WOS:000325686800005 PM 24126328 ER PT J AU Potash, J Anderson, KC AF Potash, Jesse Anderson, Kenneth C. TI Announcing the AACR Cancer Progress Report 2013 SO CLINICAL CANCER RESEARCH LA English DT Editorial Material C1 [Potash, Jesse; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Potash, J (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2013 VL 19 IS 20 BP 5545 EP 5545 DI 10.1158/1078-0432.CCR-13-2431 PG 1 WC Oncology SC Oncology GA 236LH UT WOS:000325797600001 PM 24130218 ER PT J AU Metzger, O Winer, EP Krop, I AF Metzger-Filho, Otto Winer, Eric P. Krop, Ian TI Pertuzumab: Optimizing HER2 Blockade SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; METASTATIC BREAST-CANCER; TRASTUZUMAB; DOMAIN; ACTIVATION; ERBB3/HER3; DOCETAXEL; MECHANISM; SURVIVAL; THERAPY AB Pertuzumab has been approved by the U.S. Food and Drug Administration for use in combination with trastuzumab and docetaxel for the first-line treatment of patients with advanced HER2-positive (HER2(+)) breast cancer. Pertuzumab is a recombinant humanized monoclonal antibody that binds to the extracellular dimerization domain II of HER2 and inhibits heterodimerization of HER2 with other HER family members, including EGF receptor (EGFR), HER3, and HER4. The HER2-HER3 heterodimer is a robust activator of phosphoinositide 3-kinase (PI3K) pathway signaling and functions as the most transforming and mitogenic of the receptor complexes formed by the HER family of proteins; thus, blockade of HER2-HER3 likely represents the most relevant action of pertuzumab. In the seminal phase III study, patients with HER2(+) metastatic breast cancer were randomized to receive trastuzumab and docetaxel, with or without pertuzumab: Addition of pertuzumab significantly prolonged progression-free survival with an increase of 6.1 months (12.4 vs. 18.5 months, respectively). In a subsequent analysis with 30 months of median follow-up, pertuzumab conferred a 34% reduction in the risk of mortality. Here, we review the mechanism of action of pertuzumab, the rationale for combining it with trastuzumab/pertuzumab, clinical data, and future directions for this work. (C) 2013 AACR. C1 [Metzger-Filho, Otto; Winer, Eric P.; Krop, Ian] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Metzger, O (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Yawkey 1238, Boston, MA 02115 USA. EM otto_metzger@dfci.harvard.edu FU Susan G. Komen for the Cure; ACT NOW Fund FX This work was supported in part by Susan G. Komen for the Cure (to E. P. Winer, I. Krop) and the ACT NOW Fund (to E. P. Winer). NR 21 TC 15 Z9 16 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2013 VL 19 IS 20 BP 5552 EP 5556 DI 10.1158/1078-0432.CCR-13-0518 PG 5 WC Oncology SC Oncology GA 236LH UT WOS:000325797600004 PM 23942091 ER PT J AU de Haart, SJ van de Donk, NWCJ Minnema, MC Huang, JH Aarts-Riemens, T Bovenschen, N Yuan, HP Groen, RWJ McMillin, DW Jakubikova, J Lokhorst, HM Martens, AC Mitsiades, CS Mutis, T AF de Haart, Sanne J. van de Donk, Niels W. C. J. Minnema, Monique C. Huang, Julie H. Aarts-Riemens, Tineke Bovenschen, Niels Yuan, Huipin Groen, Richard W. J. McMillin, Douglas W. Jakubikova, Jana Lokhorst, Henk M. Martens, Anton C. Mitsiades, Constantine S. Mutis, Tuna TI Accessory Cells of the Microenvironment Protect Multiple Myeloma from T-Cell Cytotoxicity through Cell Adhesion-Mediated Immune Resistance SO CLINICAL CANCER RESEARCH LA English DT Article ID MINOR HISTOCOMPATIBILITY ANTIGEN; BONE-MARROW MICROENVIRONMENT; DRUG-RESISTANCE; ADOPTIVE IMMUNOTHERAPY; TUMOR MICROENVIRONMENT; DOWN-REGULATION; DEATH; DISEASE; CONTRIBUTOR; INTEGRINS AB Purpose: Cellular immunotherapy frequently fails to induce sustained remissions in patients with multiple myeloma, indicating the ability of multiple myeloma cells to evade cellular immunity. Toward a better understanding and effective therapeutic modulation of multiple myeloma immune evasion mechanisms, we here investigated the role of the tumor microenvironment in rendering multiple myeloma cells resistant to the cytotoxic machinery of T cells. Experimental Design: Using a compartment-specific, bioluminescence imaging-based assay system, we measured the lysis of luciferase-transduced multiple myeloma cells by CD4(+) or CD8(+) CTLs in the presence versus absence of adherent accessory cells of the bone marrow microenvironment. We simultaneously determined the level of CTL activation by measuring the granzyme B release in culture supernatants. Results: Bone marrow stromal cells from patients with multiple myeloma and healthy individuals, as well as vascular endothelial cells, significantly inhibited the lysis of multiple myeloma cells in a cell-cell contact-dependent manner and without substantial T-cell suppression, thus showing the induction of a cell adhesion-mediated immune resistance (CAM-IR) against CTL lysis. Further analyses revealed that adhesion to accessory cells downregulated Fas and upregulated the caspase-3 inhibitor survivin in multiple myeloma cells. Reconstitution of Fas expression with bortezomib enhanced the CTL-mediated lysis of multiple myeloma cells. Repressing survivin with the small-molecule YM155 synergized with CTLs and abrogated CAM-IR in vitro and in vivo. Conclusion: These results reveal the cell adhesion-mediated induction of apoptosis resistance as a novel immune escape mechanism and provide a rationale to improve the efficacy of cellular therapies by pharmacologic modulation of CAM-IR. (C) 2013 AACR. C1 [de Haart, Sanne J.; Huang, Julie H.; Aarts-Riemens, Tineke; Mutis, Tuna] Univ Med Ctr Utrecht, Dept Clin Chem & Hematol, NL-3584 CX Utrecht, Netherlands. [van de Donk, Niels W. C. J.; Minnema, Monique C.; Lokhorst, Henk M.] Univ Med Ctr Utrecht, Dept Hematol, NL-3584 CX Utrecht, Netherlands. [Bovenschen, Niels] Univ Med Ctr Utrecht, Dept Pathol, NL-3584 CX Utrecht, Netherlands. [Groen, Richard W. J.; Martens, Anton C.] Univ Med Ctr Utrecht, Dept Cell Biol, NL-3584 CX Utrecht, Netherlands. [Martens, Anton C.] Univ Med Ctr Utrecht, Dept Immunol, NL-3584 CX Utrecht, Netherlands. [Yuan, Huipin] Xpand Biotechnol BV, Bilthoven, Netherlands. [van de Donk, Niels W. C. J.; Groen, Richard W. J.; McMillin, Douglas W.; Jakubikova, Jana; Mitsiades, Constantine S.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Mutis, T (reprint author), Univ Med Ctr Utrecht, Dept Clin Chem & Hematol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. EM tmutis@umcutrecht.nl OI Groen, Richard/0000-0002-5010-4604 FU Dutch Cancer Society; NIH FX This work was supported by the Dutch Cancer Society (to N.W.C.J. van de Donk) and the NIH (to C. S. Mitsiades). NR 41 TC 16 Z9 16 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2013 VL 19 IS 20 BP 5591 EP 5601 DI 10.1158/1078-0432.CCR-12-3676 PG 11 WC Oncology SC Oncology GA 236LH UT WOS:000325797600009 PM 24004671 ER PT J AU Warren, RS Atreya, CE Niedzwiecki, D Weinberg, VK Donner, DB Mayer, RJ Goldberg, RM Compton, CC Zuraek, MB Ye, C Saltz, LB Bertagnolli, MM AF Warren, Robert S. Atreya, Chloe E. Niedzwiecki, Donna Weinberg, Vivian K. Donner, David B. Mayer, Robert J. Goldberg, Richard M. Compton, Carolyn C. Zuraek, Marlene B. Ye, Cynthia Saltz, Leonard B. Bertagnolli, Monica M. TI Association of TP53 Mutational Status and Gender with Survival after Adjuvant Treatment for Stage III Colon Cancer: Results of CALGB 89803 SO CLINICAL CANCER RESEARCH LA English DT Article ID ZINC-BINDING DOMAIN; LONG-TERM SURVIVAL; COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; POOR SURVIVAL; P53 MUTATIONS; BREAST-CANCER; TUMOR SITE; FLUOROURACIL; LEUCOVORIN AB Purpose: The TP53 tumor suppressor is frequently mutated in colon cancer, but the influence of such mutations on survival remains controversial. We investigated whether mutations in the DNA-binding domain of TP53 are associated with survival in stage III colon cancer. Experimental Design: The impact of TP53 genotype was prospectively evaluated in Cancer and Leukemia Group B 89803, a trial that randomized stage III colon cancer patients to receive adjuvant 5-fluorouracil/leucovorin (5FU/LV) or 5FU/LV with irinotecan (IFL). Results: TP53 mutations were identified in 274 of 607 cases. The presence of any TP53 mutation did not predict disease-free survival (DFS) or overall survival with either adjuvant regimen when men and women were considered together or as separate groups. However, outcome differences among women became apparent when tumor TP53 genotype was stratified as wild-type versus zinc-or non-zinc-binding mutations in the TP53 DNA-binding domain. DFS at 5 years was 0.59, 0.52, and 0.78 for women with TP53 wild-type tumors, and tumors with zinc-or non-zinc-binding mutations, respectively. Survival at 5 years for these same women was 0.72, 0.59, and 0.90, respectively. No differences in survival by TP53 genotype were observed in men. Conclusions: The presence of any TP53 mutation within the DNA-binding domain did not predict survival in stage III colon cancer. However, TP53 genotype was predictive of survival in women following adjuvant therapy. Future colon cancer therapeutic trials, with inclusion of correlative molecular markers, should be designed to permit evaluation of survival and/or response to treatment in women separately from men. (C) 2013 AACR. C1 [Warren, Robert S.; Atreya, Chloe E.; Weinberg, Vivian K.; Donner, David B.; Zuraek, Marlene B.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94115 USA. [Niedzwiecki, Donna; Ye, Cynthia] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Alliance Stat & Data Ctr, Durham, NC USA. [Mayer, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bertagnolli, Monica M.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Goldberg, Richard M.] Ohio State Univ, Columbus, OH 43210 USA. [Compton, Carolyn C.] NCI, Bethesda, MD 20892 USA. [Saltz, Leonard B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Warren, RS (reprint author), Univ Calif San Francisco, Dept Surg, Helen Diller Family Comprehens Canc Ctr, 1600 Divisadero St, San Francisco, CA 94115 USA. EM robert.warren@ucsfmedctr.org RI Goldberg , Richard/M-1311-2013; OI Saltz, Leonard/0000-0001-8353-4670 FU NIH [RO184018]; American Cancer Society [11-183-01-TBG]; American Society of Clinical Oncology; Edmund Wattis Littlefield Foundation; Cancer and Leukemia Group B Foundation; Conquer Cancer Foundation of the American Society of Clinical Oncology FX This work is supported by NIH, The American Cancer Society, The American Society of Clinical Oncology, the Edmund Wattis Littlefield Foundation, and the Cancer and Leukemia Group B Foundation. R.S. Warren was supported by a grant from the NIH (RO184018) and by the Edmund Wattis Littlefield Foundation. C.E. Atreya is supported by Postdoctoral Fellowship 11-183-01-TBG from the American Cancer Society and Young Investigator Awards from the Conquer Cancer Foundation of the American Society of Clinical Oncology and the Alliance for Clinical Trials in Oncology. NR 39 TC 10 Z9 10 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2013 VL 19 IS 20 BP 5777 EP 5787 DI 10.1158/1078-0432.CCR-13-0351 PG 11 WC Oncology SC Oncology GA 236LH UT WOS:000325797600026 PM 23983256 ER PT J AU Akbareian, SE Nagy, N Steiger, CE Mably, JD Miller, SA Hotta, R Molnar, D Goldstein, AM AF Akbareian, Sophia E. Nagy, Nandor Steiger, Casey E. Mably, John D. Miller, Sarah A. Hotta, Ryo Molnar, David Goldstein, Allan M. TI Enteric neural crest-derived cells promote their migration by modifying their microenvironment through tenascin-C production SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Enteric nervous system; Extracellular matrix; Neural crest cells; Tenascin-C; Hirschsprung disease ID PRESUMPTIVE AGANGLIONIC BOWEL; TYROSINE KINASE RET; NERVOUS-SYSTEM; CHORIOALLANTOIC MEMBRANE; EXTRACELLULAR-MATRIX; NEURITE OUTGROWTH; MESSENGER-RNA; CHICK-EMBRYO; GUT; EXPRESSION AB The enteric nervous system (ENS) is derived from vagal and sacral neural crest cells that migrate, proliferate, and differentiate into enteric neurons and glia within the gut wall. The mechanisms regulating enteric neural crest-derived cell (ENCC) migration are poorly characterized despite the importance of this process in gut formation and function. Characterization of genes involved in ENCC migration is essential to understand ENS development and could provide targets for treatment of human ENS disorders. We identified the extracellular matrix glycoprotein tenascin-C (TNC) as an important regulator of ENCC development. We find TNC dynamically expressed during avian gut development. It is absent from the cecal region just prior to ENCC arrival, but becomes strongly expressed around ENCCs as they enter the ceca and hindgut In aganglionic hindguts, 'INC expression is strong throughout the outer mesenchyme, but is absent from the submucosal region, supporting the presence of both ENCC-dependent and independent expression within the gut wall. Using rat-chick coelomic grafts, neural tube cultures, and gut explants, we show that ENCCs produce TNC and that this ECM protein promotes their migration. Interestingly, only vagal neural crest-derived ENCCs express TNC, whereas sacral neural crest-derived cells do not. These results demonstrate that vagal crest-derived ENCCs actively modify their microenvironment through TNC expression and thereby help to regulate their own migration. (C) 2013 Elsevier Inc. All rights reserved. C1 [Akbareian, Sophia E.; Steiger, Casey E.; Miller, Sarah A.; Hotta, Ryo; Goldstein, Allan M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA 02114 USA. [Nagy, Nandor; Molnar, David] Semmelweis Univ, Fac Med, Dept Human Morphol & Dev Biol, H-1094 Budapest, Hungary. [Mably, John D.] Harvard Univ, Childrens Hosp Boston, Sch Med, Dept Pediat, Boston, MA 02114 USA. [Mably, John D.] Harvard Univ, Childrens Hosp Boston, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Goldstein, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Warren 1153, Boston, MA 02114 USA. EM agoldstein@partners.org FU NIH-NIDDK [R01 DK080914]; Bolyai Fellowship [Tamop-4.2.2/B-10/1 -2010-2013]; Uehara Memorial Foundation FX AMG is supported by NIH-NIDDK R01 DK080914. NN is supported by a Bolyai Fellowship and Tamop-4.2.2/B-10/1 -2010-2013. RH is supported by a grant from the Uehara Memorial Foundation. Antibodies for TNC, Fibronectin, Laminin, N-cadherin, and 8F3 were obtained from the Developmental Studies Hybridoma Bank, developed under the auspices of the NICHD and maintained by The University of Iowa. NR 57 TC 15 Z9 15 U1 0 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD OCT 15 PY 2013 VL 382 IS 2 BP 446 EP 456 DI 10.1016/j.ydbio.2013.08.006 PG 11 WC Developmental Biology SC Developmental Biology GA 234UW UT WOS:000325670800007 PM 23958436 ER PT J AU Bailey, JNC Sobrin, L Pericak-Vance, MA Haines, JL Hammond, CJ Wiggs, JL AF Bailey, Jessica N. Cooke Sobrin, Lucia Pericak-Vance, Margaret A. Haines, Jonathan L. Hammond, Christopher J. Wiggs, Janey L. TI Advances in the genomics of common eye diseases SO HUMAN MOLECULAR GENETICS LA English DT Review ID AGE-RELATED MACULOPATHY; OPEN-ANGLE GLAUCOMA; COMPLEMENT FACTOR-H; PROLIFERATIVE DIABETIC-RETINOPATHY; CENTRAL CORNEAL THICKNESS; HIGH-GRADE MYOPIA; BEAVER DAM EYE; OXIDASE-LIKE 1; MACULAR DEGENERATION; WIDE ASSOCIATION AB Genome-wide association studies (GWAS) and other genomic technologies have accelerated the discovery of genes and genomic regions contributing to common human ocular disorders with complex inheritance. Age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma and myopia account for the majority of visual impairment worldwide. Over 19 genes and/or genomic regions have been associated with AMD. Current investigations are assessing the clinical utility of risk score panels and therapies targeting disease-specific pathways. DR is the leading cause of blindness in the United States and globally is a major cause of vision loss. Genomic investigations have identified molecular pathways associated with DR in animal models which could suggest novel therapeutic targets. Three types of glaucoma, primary-open-angle glaucoma (POAG), angle-closure glaucoma and exfoliation syndrome (XFS) glaucoma, are common age-related conditions. Five genomic regions have been associated with POAG, three with angle-closure glaucoma and one with XFS. Myopia causes substantial ocular morbidity throughout the world. Recent large GWAS have identified 20 associated loci for this condition. In this report, we present a comprehensive overview of the genes and genomic regions contributing to disease susceptibility for these common blinding ocular disorders and discuss the next steps toward translation to effective gene-based screening tests and novel therapies targeting the molecular events contributing to disease. C1 [Bailey, Jessica N. Cooke; Haines, Jonathan L.] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN USA. [Sobrin, Lucia; Wiggs, Janey L.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Pericak-Vance, Margaret A.] Univ Miami, Miller Sch Med, Hussman Inst Human Genom, Miami, FL 33136 USA. [Hammond, Christopher J.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England. RP Wiggs, JL (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM janey_wiggs@meei.harvard.edu OI Hammond, Christopher/0000-0002-3227-2620 FU NIH/NEI [EY022302, EY012118, EY021453, EY022305, EY020928] FX The authors acknowledge funding support from NIH/NEI grants EY022302 (L.S.), EY012118 (M.A.P.-V.), EY021453 (J.L.H.), EY022305 (J.L.W.), EY020928 (J.L.W.). NR 93 TC 23 Z9 23 U1 1 U2 29 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 15 PY 2013 VL 22 SI 1 BP R59 EP R65 DI 10.1093/hmg/ddt396 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 230LH UT WOS:000325340500010 ER PT J AU Pore, D Parameswaran, N Matsui, K Stone, MB Saotome, I McClatchey, AI Veatch, SL Gupta, N AF Pore, Debasis Parameswaran, Neetha Matsui, Ken Stone, Matthew B. Saotome, Ichiko McClatchey, Andrea I. Veatch, Sarah L. Gupta, Neetu TI Ezrin Tunes the Magnitude of Humoral Immunity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL ANTIGEN RECEPTOR; LIPID RAFTS REVEALS; ACTIVATED B-CELLS; MHC CLASS-II; ERM PROTEINS; LYMPHOCYTE-ACTIVATION; FATE DECISION; ORGANIZATION; EXPRESSION; MICE AB Ezrin is a member of the ezrin-radixin-moesin family of membrane-actin cytoskeleton cross-linkers that participate in a variety of cellular processes. In B cells, phosphorylation of ezrin at different sites regulates multiple processes, such as lipid raft coalescence, BCR diffusion, microclustering, and endosomal JNK activation. In this study, we generated mice with conditional deletion of ezrin in the B cell lineage to investigate the physiological significance of ezrin's function in Ag receptor-mediated B cell activation and humoral immunity. B cell development, as well as the proportion and numbers of major B cell subsets in peripheral lymphoid organs, was unaffected by the loss of ezrin. Using superresolution imaging methods, we show that, in the absence of ezrin, BCRs respond to Ag binding by accumulating into larger and more stable signaling microclusters. Loss of ezrin led to delayed BCR capping and accelerated lipid raft coalescence. Although proximal signaling proteins showed stronger activation in the absence of ezrin, components of the distal BCR signaling pathways displayed distinct effects. Ezrin deficiency resulted in increased B cell proliferation and differentiation into Ab-secreting cells ex vivo and stronger T cell-independent and -dependent responses to Ag in vivo. Overall, our data demonstrate that ezrin regulates amplification of BCR signals and tunes the strength of B cell activation and humoral immunity. C1 [Pore, Debasis; Parameswaran, Neetha; Matsui, Ken; Gupta, Neetu] Cleveland Clin, Lerner Res Inst, Dept Immunol, Cleveland, OH 44195 USA. [Stone, Matthew B.; Veatch, Sarah L.] Univ Michigan, Dept Biophys, Ann Arbor, MI 48109 USA. [Saotome, Ichiko; McClatchey, Andrea I.] Massachusetts Gen Hosp, Ctr Canc, Dept Pathol, Charlestown, MA 02129 USA. [Saotome, Ichiko; McClatchey, Andrea I.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Gupta, N (reprint author), Cleveland Clin, Lerner Res Inst, Dept Immunol, 9500 Euclid Ave,NE40, Cleveland, OH 44195 USA. EM guptan@ccf.org RI Veatch, Sarah/G-9512-2016 OI Veatch, Sarah/0000-0002-9317-2308 FU National Institute of Allergy and Infectious Diseases [AI081743]; National Institute of Diabetes and Digestive and Kidney Diseases [DK068242]; Cancer Research Institute; National Institute of General Medical Sciences [GM087810] FX This work was supported by Grant AI081743 from the National Institute of Allergy and Infectious Diseases, Grant DK068242 from the National Institute of Diabetes and Digestive and Kidney Diseases, an Investigator Award from the Cancer Research Institute (to N.G.), and Grant GM087810 from the National Institute of General Medical Sciences (to S.L.V.). NR 54 TC 8 Z9 8 U1 0 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2013 VL 191 IS 8 BP 4048 EP 4058 DI 10.4049/jimmunol.1301315 PG 11 WC Immunology SC Immunology GA 232IT UT WOS:000325487700011 PM 24043890 ER PT J AU Chen, HW King, K Tu, J Sanchez, M Luster, AD Shresta, S AF Chen, Hui-Wen King, Kevin Tu, Jui Sanchez, Marisa Luster, Andrew D. Shresta, Sujan TI The Roles of IRF-3 and IRF-7 in Innate Antiviral Immunity against Dengue Virus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERFERON RESPONSE; INFECTION; MICE; REPLICATION; TRAFFICKING; MACROPHAGES; RESISTANCE; SURVIVAL; CXCR3 AB We investigated the roles of IFN regulatory factor (IRF)-3 and IRF-7 in innate antiviral immunity against dengue virus (DENV). Double-deficient Irf-3(-/-)7(-/-) mice infected with the DENV2 strain S221 possessed 1,000-150,000 fold higher levels of viral RNA than wild-type and single-deficient mice 24 h postinfection (hpi); however, they remained resistant to lethal infection. IFN-alpha/beta was induced similarly in wild-type and Irf-3(-/-) mice post-DENV infection, whereas in the Irf-7(-/-) and Irf-3(-/-)7(-/-) mice, significantly low levels of IFN-alpha/beta expression was observed within 24 hpi. IFN-stimulated gene induction was also delayed in Irf-3(-/-)7(-/-) mice relative to wild-type and single-deficient mice. In particular, Cxcl10 and Ifn alpha 2 were rapidly induced independently of both IRF-3 and IRF-7 in the Irf-3(-/-)7(-/-) mice with DENV infection. Higher levels of serum IFN-gamma, IL-6, CXCL10, IL-8, IL-12 p70, and TNF were also observed in Irf-3(-/-)7(-/-) mice 24 hpi, at which time point viral titers peaked and started to be cleared. Ab-mediated blockade experiments revealed that IFN-gamma, CXCL10, and CXCR3 function to restrict DENV replication in Irf-3(-/-)7(-/-) mice. Additionally, the IFN-stimulated genes Cxcl10, Ifit1, Ifit3, and Mx2 can be induced via an IRF-3- and IRF-7-independent pathway that does not involve IFN-gamma signaling for protection against DENV. Collectively, these results demonstrate that IRF-3 and IRF-7 are redundant, albeit IRF-7 plays a more important role than IRF-3 in inducing the initial IFN-alpha/beta response; only the combined actions of IRF-3 and IRF-7 are necessary for efficient control of early DENV infection; and the late, IRF-3- and IRF-7-independent pathway contributes to anti-DENV immunity. C1 [Chen, Hui-Wen; King, Kevin; Tu, Jui; Sanchez, Marisa; Shresta, Sujan] Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA. [Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol, Boston, MA 02115 USA. RP Shresta, S (reprint author), Jolla Inst Allergy & Immunol, Div Vaccine Discovery, 9420 Athena Circle, La Jolla, CA 92037 USA. EM sujan@liai.org OI CHEN, HUI-WEN/0000-0002-0595-3420 FU National Institutes of Health from the Southeast Regional Center of Excellence for Emerging Infections and Biodefense [U01 AI082185, U54 AI057157]; National Institute of Allergy and Infectious Diseases [HHSN272200900042C] FX This work was supported by National Institutes of Health Grants U01 AI082185 and U54 AI057157 from the Southeast Regional Center of Excellence for Emerging Infections and Biodefense and National Institute of Allergy and Infectious Diseases Contract HHSN272200900042C. NR 25 TC 27 Z9 30 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2013 VL 191 IS 8 BP 4194 EP 4201 DI 10.4049/jimmunol.1300799 PG 8 WC Immunology SC Immunology GA 232IT UT WOS:000325487700026 PM 24043884 ER PT J AU Yeung, MY McGrath, MM Nakayama, M Shimizu, T Boenisch, O Magee, CN Abdoli, R Akiba, H Ueno, T Turka, LA Najafian, N AF Yeung, Melissa Y. McGrath, Martina M. Nakayama, Masafumi Shimizu, Tetsunosuke Boenisch, Olaf Magee, Ciara N. Abdoli, Rozita Akiba, Hisaya Ueno, Takuya Turka, Laurence A. Najafian, Nader TI Interruption of Dendritic Cell-Mediated TIM-4 Signaling Induces Regulatory T Cells and Promotes Skin Allograft Survival SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IN-VIVO; APOPTOTIC CELLS; TGF-BETA; PHOSPHATIDYLSERINE RECEPTOR; TOLERANCE; ANTIGEN; DIFFERENTIATION; IMMUNOGLOBULIN; AUTOIMMUNITY; HOMEOSTASIS AB Dendritic cells (DCs) are the central architects of the immune response, inducing inflammatory or tolerogenic immunity, dependent on their activation status. As such, DCs are highly attractive therapeutic targets and may hold the potential to control detrimental immune responses. TIM-4, expressed on APCs, has complex functions in vivo, acting both as a costimulatory molecule and a phosphatidylserine receptor. The effect of TIM-4 costimulation on T cell activation remains unclear. In this study, we demonstrate that Ab blockade of DC-expressed TIM-4 leads to increased induction of induced regulatory T cells (iTregs) from naive CD4(+) T cells, both in vitro and in vivo. iTreg induction occurs through suppression of IL-4/STAT6/Gata3-induced Th2 differentiation. In addition, blockade of TIM-4 on previously activated DCs still leads to increased iTreg induction. iTregs induced under TIM-4 blockade have equivalent potency to control and, upon adoptive transfer, significantly prolong skin allograft survival in vivo. In RAG(-/-) recipients of skin allografts adoptively transferred with CD4(+) T cells, we show that TIM-4 blockade in vivo is associated with a 3-fold prolongation in allograft survival. Furthermore, in this mouse model of skin transplantation, increased induction of allospecific iTregs and a reduction in T effector responses were observed, with decreased Th1 and Th2 responses. This enhanced allograft survival and protolerogenic skewing of the alloresponse is critically dependent on conversion of naive CD4(+) to Tregs in vivo. Collectively, these studies identify blockade of DC-expressed TIM-4 as a novel strategy that holds the capacity to induce regulatory immunity in vivo. C1 [Yeung, Melissa Y.; McGrath, Martina M.; Shimizu, Tetsunosuke; Boenisch, Olaf; Magee, Ciara N.; Abdoli, Rozita; Ueno, Takuya; Najafian, Nader] Harvard Univ, Sch Med, Transplantat Res Ctr, Brigham & Womens Hosp,Renal Div, Boston, MA 02115 USA. [Nakayama, Masafumi] Tohoku Univ, Dept Immunobiol, Inst Dev Aging & Canc, Sendai, Miyagi 9808575, Japan. [Akiba, Hisaya] Juntendo Univ, Sch Med, Dept Immunol, Tokyo 1338421, Japan. [Turka, Laurence A.] Harvard Univ, Sch Med, Transplantat Biol Res Ctr, Dept Surg,Massachusetts Gen Hosp, Boston, MA 02129 USA. [Najafian, Nader] Cleveland Clin Florida, Dept Nephrol, Weston, FL 33331 USA. RP Najafian, N (reprint author), Harvard Univ, Sch Med, Transplantat Res Ctr, Brigham & Womens Hosp, 221 Longwood Ave, Boston, MA 02115 USA. EM nnajafian@rics.bwh.harvard.edu FU National Kidney Foundation; American Heart Association; National Institutes of Health [R01AI037691-17A1, R56AI089777-01A1, R56 AI101150-0141] FX This work was supported by a postdoctoral fellowship from the National Kidney Foundation (to M.Y.Y.), a fellow-to-faculty transition grant from the American Heart Association (to M.Y.Y.), and National Institutes of Health Grants R01AI037691-17A1 (to L.A.T.) and R56AI089777-01A1 and R56 AI101150-0141 (to N.N.). NR 44 TC 12 Z9 14 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2013 VL 191 IS 8 BP 4447 EP 4455 DI 10.4049/jimmunol.1300992 PG 9 WC Immunology SC Immunology GA 232IT UT WOS:000325487700052 PM 24038092 ER PT J AU Yancy, CW Jessup, M Bozkurt, B Butler, J Casey, DE Drazner, MH Fonarow, GC Geraci, SA Horwich, T Januzzi, JL Johnson, MR Kasper, EK Levy, WC Masoudi, FA McBride, PE McMurray, JJV Mitchell, JE Peterson, PN Riegel, B Sam, F Stevenson, LW Tang, WHW Tsai, EJ Wilkoff, BL Anderson, JL Jacobs, AK Halperin, JL Albert, NM Bozkurt, B Brindis, RG Creager, MA Curtis, LH DeMets, D Guyton, RA Hochman, JS Kovacs, RJ Kushner, FG Ohman, EM Pressler, SJ Sellke, FW Shen, WK Stevenson, WG Yancy, CW AF Yancy, Clyde W. Jessup, Mariell Bozkurt, Biykem Butler, Javed Casey, Donald E., Jr. Drazner, Mark H. Fonarow, Gregg C. Geraci, Stephen A. Horwich, Tamara Januzzi, James L. Johnson, Maryl R. Kasper, Edward K. Levy, Wayne C. Masoudi, Frederick A. McBride, Patrick E. McMurray, John J. V. Mitchell, Judith E. Peterson, Pamela N. Riegel, Barbara Sam, Flora Stevenson, Lynne W. Tang, W. H. Wilson Tsai, Emily J. Wilkoff, Bruce L. Anderson, Jeffrey L. Jacobs, Alice K. Halperin, Jonathan L. Albert, Nancy M. Bozkurt, Biykem Brindis, Ralph G. Creager, Mark A. Curtis, Lesley H. DeMets, David Guyton, Robert A. Hochman, Judith S. Kovacs, Richard J. Kushner, Frederick G. Ohman, E. Magnus Pressler, Susan J. Sellke, Frank W. Shen, Win-Kuang Stevenson, William G. Yancy, Clyde W. TI 2013 ACCF/AHA Guideline for the Management of Heart Failure: Executive Summary SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE ACCF/AHA Practice Guidelines; cardio-renal physiology/pathophysiology; congestive heart failure; CV surgery: transplantation, ventricular assistance, cardiomyopathy; epidemiology; health policy and outcome research; heart failure; other heart failure ID LEFT-VENTRICULAR DYSFUNCTION; BRAIN NATRIURETIC PEPTIDE; ASSOCIATION TASK-FORCE; RANDOMIZED CONTROLLED-TRIAL; CARDIAC-RESYNCHRONIZATION THERAPY; CONVERTING-ENZYME-INHIBITORS; MECHANICAL CIRCULATORY SUPPORT; ACUTE MYOCARDIAL-INFARCTION; POSITIVE AIRWAY PRESSURE; PLACEBO-CONTROLLED TRIAL C1 [Yancy, Clyde W.] Northwestern Univ, Div Cardiol, Evanston, IL 60208 USA. [Jessup, Mariell] Univ Penn, Philadelphia, PA 19104 USA. [Butler, Javed] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Casey, Donald E., Jr.] Clin Integrated Phys Network, NYU Langone Med Ctr, New York, NY USA. [Drazner, Mark H.] Univ Texas, Southwestern Med Ctr, Dallas, TX USA. [Fonarow, Gregg C.; Horwich, Tamara] Univ Calif Los Angeles, Cardiomyopathy Ctr, Los Angeles, CA USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Geraci, Stephen A.] E Tennessee State Univ, Quillen Coll Med, Johnson City, TN 37614 USA. [Januzzi, James L.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Januzzi, James L.] Massachusetts Gen Hosp, Cardiac Intens Care Unit, Boston, MA 02114 USA. [Johnson, Maryl R.] Univ Wisconsin, Madison, WI 53706 USA. [Kasper, Edward K.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Levy, Wayne C.] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Masoudi, Frederick A.] Univ Colorado, Div Cardiol, Denver, CO 80202 USA. [McBride, Patrick E.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. [McMurray, John J. V.] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Glasgow G12 8QQ, Lanark, Scotland. [Mitchell, Judith E.] Suny Downstate Med Ctr, Heart Failure Ctr, Brooklyn, NY USA. [Peterson, Pamela N.] Univ Colorado, Denver Hlth Med Ctr, Div Cardiol, Boulder, CO 80309 USA. [Riegel, Barbara] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Sam, Flora] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Div Cardiol,Cardiomyopathy Program, Boston, MA 02215 USA. [Stevenson, Lynne W.] Brigham & Womens Hosp, Cardiovasc Div, Cardiomyopathy & Heart Failure Program, Boston, MA 02115 USA. [Tang, W. H. Wilson] Cleveland Clin Fdn, Cleveland, OH USA. [Tsai, Emily J.] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [Wilkoff, Bruce L.] Cleveland Clin, Cleveland, OH USA. RP Yancy, CW (reprint author), Northwestern Univ, Div Cardiol, Evanston, IL 60208 USA. NR 380 TC 82 Z9 85 U1 1 U2 21 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 OCT 15 PY 2013 VL 62 IS 16 BP 1495 EP 1539 DI 10.1016/j.jacc.2013.05.020 PG 45 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 231NZ UT WOS:000325425100022 ER PT J AU Yarchoan, M Louneva, N Xie, SX Swenson, FJ Hu, W Soares, H Trojanowski, JQ Lee, VMY Kling, MA Shaw, LM Chen-Plotkin, A Wolk, DA Arnold, SE AF Yarchoan, Mark Louneva, Natalia Xie, Sharon X. Swenson, Frank J. Hu, William Soares, Holly Trojanowski, John Q. Lee, Virginia M. -Y. Kling, Mitchel A. Shaw, Leslie M. Chen-Plotkin, Alice Wolk, David A. Arnold, Steven E. TI Association of plasma C-reactive protein levels with the diagnosis of Alzheimer's disease SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE Alzheimer disease; Mild cognitive impairment; C-reactive protein; Inflammation; Biological markers; Apolipoprotein E ID COGNITIVE FUNCTION; INFLAMMATION; RISK; DEMENTIA; MARKER; HEALTH; CRP AB C-reactive protein (CRP) participates in the systemic response to inflammation. Previous studies report inconsistent findings regarding the relationship between plasma CRP and Alzheimer's disease (AD). We measured plasma CRP in 203 subjects with AD, 58 subjects with mild cognitive impairment (MCI) and 117 normal aging subjects and administered annual Mini-Mental State Examinations (MMSE) during a 3-year follow-up period to investigate CRP's relationship with diagnosis and progression of cognitive decline. Adjusted for age, sex, and education, subjects with AD had significantly lower levels of plasma CRP than subjects with MCI and normal aging. However, there was no significant association between plasma CRP at baseline and subsequent cognitive decline as assessed by longitudinal changes in MMSE score. Our results support previous reports of reduced levels of plasma CRP in AD and indicate its potential utility as a biomarker for the diagnosis of AD. (C) 2013 Elsevier B.V. All rights reserved. C1 [Yarchoan, Mark] Univ Penn, Dept Internal Med, Philadelphia, PA 19104 USA. [Louneva, Natalia; Arnold, Steven E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Xie, Sharon X.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Swenson, Frank J.] Pfizer Diagnost, PharmaTX Precis Med, Groton, CT USA. [Hu, William] Emory Univ, Emory Alzheimers Dis Res Ctr, Atlanta, GA 30322 USA. [Soares, Holly] Pfizer Global Res & Dev, Groton, CT USA. [Trojanowski, John Q.; Lee, Virginia M. -Y.] Univ Penn, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. [Kling, Mitchel A.] Philadelphia VA Med Ctr, Behav Hlth Serv, Philadelphia, PA USA. [Shaw, Leslie M.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. [Chen-Plotkin, Alice; Wolk, David A.; Arnold, Steven E.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. RP Arnold, SE (reprint author), 3615 Chestnut St, Philadelphia, PA 19104 USA. EM steven.arnold@uphs.upenn.edu OI Kling, Mitchel/0000-0002-2232-1409 FU National Institutes of Health [AG10124]; Penn-Pfizer Research Alliance at the University of Pennsylvania; Marian S. Ware Alzheimer's Program; Allen H. and Selma W. Berkman Charitable Trust FX This study has been supported by the National Institutes of Health (grant no. AG10124), the Penn-Pfizer Research Alliance at the University of Pennsylvania, the Marian S. Ware Alzheimer's Program, and the Allen H. and Selma W. Berkman Charitable Trust. We thank Xiaoyan Han, M.S., for her help with the statistical programming of the mixed-effects model analysis. NR 16 TC 12 Z9 12 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X EI 1878-5883 J9 J NEUROL SCI JI J. Neurol. Sci. PD OCT 15 PY 2013 VL 333 IS 1-2 BP 9 EP 12 DI 10.1016/j.jns.2013.05.028 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 235SN UT WOS:000325741100003 PM 23978419 ER PT J AU Johnson, N Johnson, SF Yao, W Li, YC Choi, YE Bernhardy, AJ Wang, YF Capelletti, M Sarosiek, KA Moreau, LA Chowdhury, D Wickramanayake, A Harrell, MI Liu, JF D'Andrea, AD Miron, A Swisher, EM Shapiro, GI AF Johnson, Neil Johnson, Shawn F. Yao, Wei Li, Yu-Chen Choi, Young-Eun Bernhardy, Andrea J. Wang, Yifan Capelletti, Marzia Sarosiek, Kristopher A. Moreau, Lisa A. Chowdhury, Dipanjan Wickramanayake, Anneka Harrell, Maria I. Liu, Joyce F. D'Andrea, Alan D. Miron, Alexander Swisher, Elizabeth M. Shapiro, Geoffrey I. TI Stabilization of mutant BRCA1 protein confers PARP inhibitor and platinum resistance SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE homologous recombination; cancer therapy ID POLY(ADP-RIBOSE) POLYMERASE; HOMOLOGOUS RECOMBINATION; OVARIAN CARCINOMAS; TUMOR SUPPRESSION; BREAST CANCERS; 53BP1; CELLS; MUTATIONS; REPAIR; CHEMOTHERAPY AB Breast Cancer Type 1 Susceptibility Protein (BRCA1)-deficient cells have compromised DNA repair and are sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. Despite initial responses, the development of resistance limits clinical efficacy. Mutations in the BRCA C-terminal (BRCT) domain of BRCA1 frequently create protein products unable to fold that are subject to protease-mediated degradation. Here, we show HSP90-mediated stabilization of a BRCT domain mutant BRCA1 protein under PARP inhibitor selection pressure. The stabilized mutant BRCA1 protein interacted with PALB2-BRCA2-RAD51, was essential for RAD51 focus formation, and conferred PARP inhibitor as well as cisplatin resistance. Treatment of resistant cells with the HSP90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin reduced mutant BRCA1 protein levels and restored their sensitivity to PARP inhibition. Resistant cells also acquired a TP53BP1 mutation that facilitated DNA end resection in the absence of a BRCA1 protein capable of binding CtIP. Finally, concomitant increased mutant BRCA1 and decreased 53BP1 protein expression occur in clinical samples of BRCA1-mutated recurrent ovarian carcinomas that have developed resistance to platinum. These results provide evidence for a two-event mechanism by which BRCA1-mutant tumors acquire anticancer therapy resistance. C1 [Johnson, Neil; Johnson, Shawn F.; Yao, Wei; Li, Yu-Chen; Capelletti, Marzia; Sarosiek, Kristopher A.; Liu, Joyce F.; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Choi, Young-Eun; Moreau, Lisa A.; Chowdhury, Dipanjan; D'Andrea, Alan D.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Miron, Alexander] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Miron, Alexander] Harvard Univ, Sch Med, Boston, MA USA. [Johnson, Neil; Liu, Joyce F.; Shapiro, Geoffrey I.] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Johnson, Neil; Moreau, Lisa A.; Liu, Joyce F.; D'Andrea, Alan D.; Shapiro, Geoffrey I.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Bernhardy, Andrea J.; Wang, Yifan] Fox Chase Canc Ctr, Dev Therapeut Program, Philadelphia, PA 19111 USA. [Moreau, Lisa A.; D'Andrea, Alan D.] Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. [Wickramanayake, Anneka; Harrell, Maria I.; Swisher, Elizabeth M.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Wickramanayake, Anneka; Harrell, Maria I.; Swisher, Elizabeth M.] Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Johnson, N (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM neil.johnson@fccc.edu; geoffrey_shapiro@dfci.harvard.edu FU Clovis; AstraZeneca; US National Institutes of Health [R01 CA090687, P50 CA089393, P50 CA090578, P50 CA83636, P30 CA006927, R01 CA142698]; Susan G. Komen Investigator Initiated Research Grant [12223953]; Susan G. Komen Career Catalyst Award [CCR12226280]; Wendy Feuer Ovarian Cancer Research Fund; American Cancer Society [RSG-12-079-01] FX Rucaparib and olaparib were supplied by Clovis and AstraZeneca, respectively. This work was supported by US National Institutes of Health Grants R01 CA090687 (to G. I. S.), P50 CA089393 [Dana-Farber/Harvard Cancer Center (DF/HCC) Specialized Program of Research Excellence (SPORE) in Breast Cancer (to G. I. S.)], P50 CA090578 [DF/HCC SPORE in Lung Cancer (to G. I. S.)], P50 CA83636 [Pacific Ovarian Cancer Research Consortium SPORE in Ovarian Cancer (to E. M. S.)], P30 CA006927 [Fox Chase Cancer Center Developmental New Investigator Funds (to N.J.)], and R01 CA142698 (to D. C.); Susan G. Komen Investigator Initiated Research Grant 12223953 (to G. I. S.); Susan G. Komen Career Catalyst Award CCR12226280 (to N.J.); the Wendy Feuer Ovarian Cancer Research Fund (to E. M. S.); and American Cancer Society Research Scholar Grant RSG-12-079-01 (to D. C.). NR 24 TC 36 Z9 36 U1 3 U2 31 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 OCT 15 PY 2013 VL 110 IS 42 BP 17041 EP 17046 DI 10.1073/pnas.1305170110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 234HT UT WOS:000325634200073 PM 24085845 ER PT J AU Chen, CH Fiecas, M Gutierrez, ED Panizzon, MS Eyler, LT Vuoksimaa, E Thompson, WK Fennema-Notestine, C Hagler, DJ Jernigan, TL Neale, MC Franz, CE Lyons, MJ Fischl, B Tsuang, MT Dale, AM Kremen, WS AF Chen, Chi-Hua Fiecas, Mark Gutierrez, E. D. Panizzon, Matthew S. Eyler, Lisa T. Vuoksimaa, Eero Thompson, Wesley K. Fennema-Notestine, Christine Hagler, Donald J., Jr. Jernigan, Terry L. Neale, Michael C. Franz, Carol E. Lyons, Michael J. Fischl, Bruce Tsuang, Ming T. Dale, Anders M. Kremen, William S. TI Genetic topography of brain morphology SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genetics; MRI; regionalization ID SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; CORTICAL SURFACE; COORDINATE SYSTEM; AREA IDENTITY; NEOCORTEX; REGIONALIZATION; SPECIFICATION; THICKNESS; PAX6 AB Animal data show that cortical development is initially patterned by genetic gradients largely along three orthogonal axes. We previously reported differences in genetic influences on cortical surface area along an anterior-posterior axis using neuroimaging data of adult human twins. Here, we demonstrate differences in genetic influences on cortical thickness along a dorsal-ventral axis in the same cohort. The phenomenon of orthogonal gradations in cortical organization evident in different structural and functional properties may originate from genetic gradients. Another emerging theme of cortical patterning is that patterns of genetic influences recapitulate the spatial topography of the cortex within hemispheres. The genetic patterning of both cortical thickness and surface area corresponds to cortical functional specializations. Intriguingly, in contrast to broad similarities in genetic patterning, two sets of analyses distinguish cortical thickness and surface area genetically. First, genetic contributions to cortical thickness and surface area are largely distinct; there is very little genetic correlation (i.e., shared genetic influences) between them. Second, organizing principles among genetically defined regions differ between thickness and surface area. Examining the structure of the genetic similarity matrix among clusters revealed that, whereas surface area clusters showed great genetic proximity with clusters from the same lobe, thickness clusters appear to have close genetic relatedness with clusters that have similar maturational timing. The discrepancies are in line with evidence that the two traits follow different mechanisms in neurodevelopment. Our findings highlight the complexity of genetic influences on cortical morphology and provide a glimpse into emerging principles of genetic organization of the cortex. C1 [Chen, Chi-Hua; Fiecas, Mark; Panizzon, Matthew S.; Eyler, Lisa T.; Vuoksimaa, Eero; Thompson, Wesley K.; Fennema-Notestine, Christine; Jernigan, Terry L.; Franz, Carol E.; Tsuang, Ming T.; Kremen, William S.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Gutierrez, E. D.; Jernigan, Terry L.] Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA. [Fennema-Notestine, Christine; Hagler, Donald J., Jr.; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Chen, Chi-Hua; Fiecas, Mark; Panizzon, Matthew S.; Vuoksimaa, Eero; Franz, Carol E.; Tsuang, Ming T.; Kremen, William S.] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA. [Tsuang, Ming T.] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA. [Kremen, William S.] Vet Affairs San Diego Healthcare Syst, Ctr Excellence Stress & Mental Hlth, La Jolla, CA 92161 USA. [Eyler, Lisa T.] Vet Affairs San Diego Healthcare Syst, Vet Integrated Serv Network 22, Mental Illness Res Educ & Clin Ctr, La Jolla, CA 92161 USA. [Lyons, Michael J.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23220 USA. [Neale, Michael C.] Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA 23220 USA. [Fischl, Bruce] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Fischl, Bruce] Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lyons, Michael J.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Vuoksimaa, Eero] Univ Helsinki, Dept Publ Hlth, FI-00014 Helsinki, Finland. [Fischl, Bruce] MIT Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. RP Chen, CH (reprint author), Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. EM chc101@ucsd.edu OI Lyons, Michael/0000-0001-6516-9219; Fennema-Notestine, Christine/0000-0002-6527-6361 FU National Institute on Aging [AG022381, AG018386, AG018384, AG022982, AG031224]; National Institute on Drug Abuse [DA029475]; National Institute of Neurological Disorders and Stroke [NS056883]; Academy of Finland [257075]; US Department of Veterans Affairs FX This work was funded by National Institute on Aging Grants AG022381, AG018386, AG018384, AG022982, and AG031224; National Institute on Drug Abuse Grant DA029475; National Institute of Neurological Disorders and Stroke Grant NS056883; and Academy of Finland Grant 257075 (to E. V.). The US Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. NR 51 TC 50 Z9 50 U1 2 U2 14 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 OCT 15 PY 2013 VL 110 IS 42 BP 17089 EP 17094 DI 10.1073/pnas.1308091110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 234HT UT WOS:000325634200081 PM 24082094 ER PT J AU Satpute, AB Wager, TD Cohen-Adad, J Bianciardi, M Choi, JK Buhle, JT Wald, LL Barrett, LF AF Satpute, Ajay B. Wager, Tor D. Cohen-Adad, Julien Bianciardi, Marta Choi, Ji-Kyung Buhle, Jason T. Wald, Lawrence L. Barrett, Lisa Feldman TI Identification of discrete functional subregions of the human periaqueductal gray SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE brain stem; neuroimaging; emotion; high-resolution ID HUMAN BRAIN; PEPTIDERGIC ORGANIZATION; EMOTION; PAIN; STATE; FMRI; METAANALYSIS; CIRCUITS; TESLA; FIELD AB The midbrain periaqueductal gray (PAG) region is organized into distinct subregions that coordinate survival-related responses during threat and stress [Bandler R, Keay KA, Floyd N, Price J (2000) Brain Res 53 (1):95-104]. To examine PAG function in humans, researchers have relied primarily on functional MRI (fMRI), but technological and methodological limitations have prevented researchers from localizing responses to different PAG subregions. We used high-field strength (7-T) fMRI techniques to image the PAG at high resolution (0.75 mm isotropic), which was critical for dissociating the PAG from the greater signal variability in the aqueduct. Activation while participants were exposed to emotionally aversive images segregated into subregions of the PAG along both dorsal/ventral and rostral/caudal axes. In the rostral PAG, activity was localized to lateral and dorsomedial subregions. In caudal PAG, activity was localized to the ventrolateral region. This shifting pattern of activity from dorsal to ventral PAG along the rostrocaudal axis mirrors structural and functional neurobiological observations in nonhuman animals. Activity in lateral and ventrolateral subregions also grouped with distinct emotional experiences (e. g., anger and sadness) in a factor analysis, suggesting that each subregion participates in distinct functional circuitry. This study establishes the use of high-field strength fMRI as a promising technique for revealing the functional architecture of the PAG. The techniques developed here also may be extended to investigate the functional roles of other brainstem nuclei. C1 [Satpute, Ajay B.; Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Wager, Tor D.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA. [Cohen-Adad, Julien] Ecole Polytech, Dept Elect Engn, Montreal, PQ H3T 1J4, Canada. [Bianciardi, Marta; Choi, Ji-Kyung; Wald, Lawrence L.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Barrett, Lisa Feldman] Massachusetts Gen Hosp, Dept Psychiat, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Buhle, Jason T.] Columbia Univ, Dept Psychol, New York, NY 10027 USA. RP Satpute, AB (reprint author), Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. EM a.satpute@neu.edu RI Wald, Lawrence/D-4151-2009; OI Satpute, Ajay/0000-0003-0227-0816 FU National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health (NIH); NIH Shared Instrumentation Grant Program [S10RR023043, S10RR019307, S10RR023401]; NIH [DP1OD003312]; Army Research Institute [W5J9CQ-11-C-0046]; National Institute of Mental Health [2R01MH076136, R21MH082308] FX We thank Jochen Weber for assistance with figures. This research was 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, P41EB015896, a P41 Regional Resource supported by the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health (NIH). This work involved the use of instrumentation supported by the NIH Shared Instrumentation Grant Program Grants S10RR023043, S10RR019307, and S10RR023401. This work also was funded by NIH Director's Pioneer Award DP1OD003312 (to L. F. B.), Army Research Institute Contract W5J9CQ-11-C-0046 (to L. F. B.), and by National Institute of Mental Health Grants 2R01MH076136 and R21MH082308 (both to T. D. W.). The views, opinion, and/or findings contained in this article are solely those of the authors and should not be construed as an official Department of the Army or Department of Defense position, policy, or decision. NR 44 TC 30 Z9 30 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 OCT 15 PY 2013 VL 110 IS 42 BP 17101 EP 17106 DI 10.1073/pnas.1306095110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 234HT UT WOS:000325634200083 PM 24082116 ER PT J AU Brecher, SM Novak-Weekley, SM Nagy, E AF Brecher, Stephen M. Novak-Weekley, Susan M. Nagy, Elisabeth TI Laboratory Diagnosis of Clostridium difficile Infections: There Is Light at the End of the Colon SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE Clostridium difficile; laboratory design of C. difficile; Brecher guidelines ID REAL-TIME PCR; ILLUMIGENE C.-DIFFICILE; ENZYME-IMMUNOASSAY; GLUTAMATE-DEHYDROGENASE; CLINICAL MICROBIOLOGY; CYTOTOXICITY ASSAY; EUROPEAN-SOCIETY; 2-STEP ALGORITHM; TOXIN; TESTS AB Single molecular or multistep assays (glutamate dehydrogenase, toxin A/B, +/- molecular) are recommended for the diagnosis of CDI in patients with clinically significant diarrhea. Rapid and accurate tests can improve resource allocations and improve patient care. Enzyme immunoassay (EIA) for toxins A/B is too insensitive for use as a stand-alone assay. This guideline will examine the use of molecular tests and multitest algorithms for the diagnosis of Clostridium difficile infection (CDI). These new tests, alone or in a multistep algorithm consisting of >1 assay, are more expensive than the older EIA assays; however, rapid and accurate testing can save money overall by initiating appropriate treatment and infection control protocols sooner and by possibly reducing length of hospital stay. We recommend testing only unformed stool in patients with clinically significant diarrhea by a molecular method or by a 2- to 3-step algorithm. C1 [Brecher, Stephen M.] VA Boston Healthcare Syst, Pathol & Lab Med, West Roxbury, MA 02132 USA. [Brecher, Stephen M.] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Nagy, Elisabeth] Univ Szeged, Inst Clin Microbiol, Szeged, Hungary. RP Brecher, SM (reprint author), VA Boston Healthcare Syst, Pathol & Lab Med, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM stephen.brecher@va.gov NR 55 TC 34 Z9 35 U1 0 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 15 PY 2013 VL 57 IS 8 BP 1175 EP 1181 DI 10.1093/cid/cit424 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 228EJ UT WOS:000325168100021 PM 23788237 ER PT J AU Pallin, DJ Camargo, CA AF Pallin, Daniel J. Camargo, Carlos A., Jr. TI Use of Cephalexin Plus Trimethoprim/Sulfamethoxazole vs Cephalexin Alone for Treatment of Uncomplicated Cellulitis Reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 [Pallin, Daniel J.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Pallin, DJ (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St,Neville House 304-D, Boston, MA 02115 USA. EM dpallin@partners.org RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 NR 3 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 15 PY 2013 VL 57 IS 8 BP 1217 EP 1218 DI 10.1093/cid/cit450 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 228EJ UT WOS:000325168100032 PM 23821732 ER PT J AU Buikema, JW Mady, AS Mittal, NV Atmanli, A Caron, L Doevendans, PA Sluijter, JPG Domian, IJ AF Buikema, Jan Willem Mady, Ahmed S. Mittal, Nikhil V. Atmanli, Ayhan Caron, Leslie Doevendans, Pieter A. Sluijter, Joost P. G. Domian, Ibrahim J. TI Wnt/beta-catenin signaling directs the regional expansion of first and second heart field-derived ventricular cardiomyocytes SO DEVELOPMENT LA English DT Article DE Cardiac development; Cardiomyocyte differentiation; Cardiomyocyte proliferation; First heart field; Gsk3 inhibitor; Wnt/beta-catenin; Mouse ID EMBRYONIC STEM-CELLS; SMALL-MOLECULE INHIBITORS; CARDIAC PROGENITOR CELLS; BETA-CATENIN; CARDIOVASCULAR PROGENITORS; MAMMALIAN HEART; SELF-RENEWAL; PATHWAY; DIFFERENTIATION; MOUSE AB In mammals, cardiac development proceeds from the formation of the linear heart tube, through complex looping and septation, all the while increasing in mass to provide the oxygen delivery demands of embryonic growth. The developing heart must orchestrate regional differences in cardiomyocyte proliferation to control cardiac morphogenesis. During ventricular wall formation, the compact myocardium proliferates more vigorously than the trabecular myocardium, but the mechanisms controlling such regional differences among cardiomyocyte populations are not understood. Control of definitive cardiomyocyte proliferation is of great importance for application to regenerative cell-based therapies. We have used murine and human pluripotent stem cell systems to demonstrate that, during in vitro cellular differentiation, early ventricular cardiac myocytes display a robust proliferative response to beta-cateninmediated signaling and conversely accelerate differentiation in response to inhibition of this pathway. Using gain-and loss-of-function murine genetic models, we show that beta-catenin controls ventricular myocyte proliferation during development and the perinatal period. We further demonstrate that the differential activation of the Wnt/beta-catenin signaling pathway accounts for the observed differences in the proliferation rates of the compact versus the trabecular myocardium during normal cardiac development. Collectively, these results provide a mechanistic explanation for the differences in localized proliferation rates of cardiac myocytes and point to a practical method for the generation of the large numbers of stem cell-derived cardiac myocytes necessary for clinical applications. C1 [Buikema, Jan Willem; Mady, Ahmed S.; Mittal, Nikhil V.; Atmanli, Ayhan; Domian, Ibrahim J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Buikema, Jan Willem; Mady, Ahmed S.; Mittal, Nikhil V.; Domian, Ibrahim J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Buikema, Jan Willem; Doevendans, Pieter A.; Sluijter, Joost P. G.] Univ Med Ctr Utrecht, Dept Cardiol, NL-3584 CX Utrecht, Netherlands. [Caron, Leslie] Genea FSHD, Sydney, NSW 2000, Australia. [Domian, Ibrahim J.] Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA. RP Domian, IJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charles River Plaza CPZN 3200,185 Cambridge St, Boston, MA 02114 USA. EM idomian@partners.org FU National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) [U01HL10040801, 1K08 HL091209]; Dutch Ministry of Economic Affairs, Agriculture and Innovation; Dutch Heart Foundation FX This work was supported by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) [U01HL10040801 and NIH/NHLBI 1K08 HL091209]; by project P1.04 SMARTCARE of the BioMedical Materials institute, co- funded by the Dutch Ministry of Economic Affairs, Agriculture and Innovation; and by the Dutch Heart Foundation. Deposited in PMC for release after 12 months. NR 74 TC 13 Z9 14 U1 3 U2 14 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD OCT 15 PY 2013 VL 140 IS 20 BP 4165 EP + DI 10.1242/dev.099325 PG 22 WC Developmental Biology SC Developmental Biology GA 227ZC UT WOS:000325153200006 PM 24026118 ER PT J AU Henrich, TJ Gandhi, RT AF Henrich, Timothy J. Gandhi, Rajesh T. TI Early Treatment and HIV-1 Reservoirs: A Stitch in Time? SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE HIV; antiretroviral therapy; HIV reservoirs; HIV persistence; gut-associated-lymphoid-tissue ID T-CELL SUBSETS; ANTIRETROVIRAL THERAPY; IMMUNE ACTIVATION; INFECTION; MEMORY; QUANTIFICATION; ESTABLISHMENT; PERSISTENCE; DEPLETION; DRIVEN C1 [Henrich, Timothy J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Henrich, Timothy J.; Gandhi, Rajesh T.] Harvard Univ, Sch Med, Boston, MA USA. [Gandhi, Rajesh T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Gandhi, RT (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM rgandhi@partners.org FU National Institutes of Health (NIH) [R01 AI066992-04A1, NIH G08LM008830-01, NIH U01 AI 694722]; National Institutes of Health (NIH), Harvard University Center for AIDS Research [NIH 2P30 AI060354-06]; NIH [1K23AI098480-01]; Foundation for AIDS Research (amfAR) [108466-52-RGRL]; Harvard University Center for AIDS Research [NIH P30 AI060354] FX This work was supported by the National Institutes of Health (NIH) (R01 AI066992-04A1 to R.T.G.) and NIH G08LM008830-01 (to R.T.G.) and by grants to the AIDS Clinical Trials Group (NIH U01 AI 694722) and the Harvard University Center for AIDS Research (NIH 2P30 AI060354-06) (to R.T.G.). T.J.H. is supported by the NIH (1K23AI098480-01), the Foundation for AIDS Research (amfAR) (108466-52-RGRL), and the Harvard University Center for AIDS Research (NIH P30 AI060354). NR 33 TC 5 Z9 6 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 15 PY 2013 VL 208 IS 8 BP 1189 EP 1193 DI 10.1093/infdis/jit307 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 223TJ UT WOS:000324832800001 PM 23852126 ER PT J AU Yukl, SA Shergill, AK Ho, T Killian, M Girling, V Epling, L Li, PL Wong, LK Crouch, P Deeks, SG Havlir, DV McQuaid, K Sinclair, E Wong, JK AF Yukl, Steven A. Shergill, Amandeep K. Ho, Terence Killian, Maudi Girling, Valerie Epling, Lorrie Li, Peilin Wong, Lisa K. Crouch, Pierre Deeks, Steven G. Havlir, Diane V. McQuaid, Kenneth Sinclair, Elizabeth Wong, Joseph K. TI The Distribution of HIV DNA and RNA in Cell Subsets Differs in Gut and Blood of HIV-Positive Patients on ART: Implications for Viral Persistence SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE HIV; HIV-1; ART; persistence; reservoir; CD4(+) T cell; gut; intestine; ileum; rectum ID ACTIVE ANTIRETROVIRAL THERAPY; CD4(+) T-CELLS; VIRUS TYPE-1 RNA; LYMPHOID-TISSUE; IN-VIVO; PERIPHERAL-BLOOD; CENTRAL MEMORY; INFECTION; PLASMA; RESERVOIR AB Even with optimal antiretroviral therapy, human immunodeficiency virus (HIV) persists in plasma, blood cells, and tissues. To develop new therapies, it is essential to know what cell types harbor residual HIV. We measured levels of HIV DNA, RNA, and RNA/DNA ratios in sorted subsets of CD4(+) T cells (CCR7(+), transitional memory, and effector memory) and non-CD4(+) T leukocytes from blood, ileum, and rectum of 8 ART-suppressed HIV-positive subjects. Levels of HIV DNA/million cells in CCR7(+) and effector memory cells were higher in the ileum than blood. When normalized by cell frequencies, most HIV DNA and RNA in the blood were found in CCR7(+) cells, whereas in both gut sites, most HIV DNA and RNA were found in effector memory cells. HIV DNA and RNA were observed in non-CD4(+) T leukocytes at low levels, particularly in gut tissues. Compared to the blood, the ileum had higher levels of HIV DNA and RNA in both CD4(+) T cells and non-CD4(+) T leukocytes, whereas the rectum had higher HIV DNA levels in both cell types but lower RNA levels in CD4(+) T cells. Future studies should determine whether different mechanisms allow HIV to persist in these distinct reservoirs, and the degree to which different therapies can affect each reservoir. C1 [Yukl, Steven A.; Shergill, Amandeep K.; Li, Peilin; Crouch, Pierre; McQuaid, Kenneth; Wong, Joseph K.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Yukl, Steven A.; Shergill, Amandeep K.; Ho, Terence; Killian, Maudi; Girling, Valerie; Epling, Lorrie; Li, Peilin; Crouch, Pierre; Deeks, Steven G.; Havlir, Diane V.; McQuaid, Kenneth; Sinclair, Elizabeth; Wong, Joseph K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ho, Terence; Killian, Maudi; Girling, Valerie; Epling, Lorrie; Deeks, Steven G.; Havlir, Diane V.; Sinclair, Elizabeth] San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA. [Wong, Lisa K.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. RP Yukl, SA (reprint author), San Francisco VA Med Ctr, 4150 Clement St,111W3, San Francisco, CA 94121 USA. EM steven.yukl@ucsf.edu FU US Department of Veterans Affairs [1 IK2 CX000520-01, I01 BX000192]; UCSF-Gladstone Center for AIDS Research (CFAR) [P30-AI027763]; National Institute of Allergy and Infectious Diseases at the National Institutes of Health [R56AI091573, K24 AI069994, U19AI096109] FX This work was supported by the US Department of Veterans Affairs (1 IK2 CX000520-01 [to S. Y.], I01 BX000192 [to J. W.]); the UCSF-Gladstone Center for AIDS Research (CFAR) (P30-AI027763 [to S. Y.]); and the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (R56AI091573 [J. W., S. Y., A. S., D. H.], K24 AI069994 [to S. D.], U19AI096109 [to S. D., J. W.]). NR 43 TC 42 Z9 42 U1 1 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 15 PY 2013 VL 208 IS 8 BP 1212 EP 1220 DI 10.1093/infdis/jit308 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 223TJ UT WOS:000324832800004 PM 23852128 ER PT J AU Koehler, RN Alter, G Tovanabutra, S Saathoff, E Arroyo, MA Walsh, AM Sanders-Buell, EE Maboko, L Hoelscher, M Robb, ML Michael, NL McCutchan, FE Kim, JH Kijak, GH AF Koehler, Rebecca N. Alter, Galit Tovanabutra, Sodsai Saathoff, Elmar Arroyo, Miguel A. Walsh, Anne M. Sanders-Buell, Eric E. Maboko, Leonard Hoelscher, Michael Robb, Merlin L. Michael, Nelson L. McCutchan, Francine E. Kim, Jerome H. Kijak, Gustavo H. TI Natural Killer Cell-Mediated Innate Sieve Effect on HIV-1: The Impact of KIR/HLA Polymorphism on HIV-1 Subtype-Specific Acquisition in East Africa SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE HIV-1; innate immunity; KIR; HLA; sieve effect; subtypes; East Africa ID HLA; DIVERSITY; INDIVIDUALS; TANZANIA; COMPLEX; MBEYA AB Here we explore the association between killer cell immunoglobulin-like receptor (KIR)/HLA and human immunodeficiency virus type 1 (HIV-1) acquisition with different viral subtypes circulating in East Africa. In the prospective Cohort Development (CODE) cohort (Mbeya, Tanzania), carriers of KIR3DS1 and its putative ligand (HLA-A or HLA-B Bw4-80Ile alleles) showed increased HIV-1 acquisition risk (odds ratio [OR] = 3.46; 95% confidence interval [CI], 1.12-10.63; P =. 04) and a trend for enrichment for subtype A and A-containing recombinants (78% vs 46%; OR = 4.05; 95% CI,.91-28.30; P = .09) at the expense of subtype C (11% vs 43%; OR = 0.17; 95% CI,.01-.97; P = .08). In vitro, only natural killer cells from KIR3DS1(+)/HLA-Bw4-80Ile (+) healthy donors showed a 2-fold increased capacity to inhibit replication of subtype C vs subtype A viruses (P = .01). These findings suggest the presence of an innate sieve effect and may inform HIV-1 vaccine development. C1 [Koehler, Rebecca N.; Tovanabutra, Sodsai; Arroyo, Miguel A.; Walsh, Anne M.; Sanders-Buell, Eric E.; Robb, Merlin L.; Michael, Nelson L.; McCutchan, Francine E.; Kim, Jerome H.; Kijak, Gustavo H.] US Mil HIV Res Program, Rockville, MD USA. [Koehler, Rebecca N.; Tovanabutra, Sodsai; Walsh, Anne M.; Sanders-Buell, Eric E.; Robb, Merlin L.; McCutchan, Francine E.; Kijak, Gustavo H.] Henry M Jackson Fdn, Rockville, MD USA. [Alter, Galit] Harvard Univ, Ragon Inst, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Alter, Galit] MIT, Boston, MA USA. [Saathoff, Elmar; Hoelscher, Michael] Univ Munich, Dept Infect Dis & Trop Med, D-81377 Munich, Germany. [Arroyo, Miguel A.; Michael, Nelson L.; Kim, Jerome H.] Walter Reed Army Inst Res, Div Retrovirol, Rockville, MD USA. [Maboko, Leonard; Hoelscher, Michael] NIMR Mbeya Med Res Programme, Mbeya, Tanzania. RP Kijak, GH (reprint author), Walter Reed Army Inst Res, US Mil HIV Res Program, Henry M Jackson Fdn, 503 Robert Grant Ave,Rm 2N27, Silver Spring, MD 20910 USA. EM gkijak@hivresearch.org RI Hoelscher, Michael/D-3436-2012; OI Arroyo, Miguel/0000-0001-7416-8867 FU Henry M. Jackson Foundation for the Advancement of Military Medicine; US Department of Defense (DOD); National Institute for Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH) [Y01 AI2642-12]; DOD; NIAID/NIH FX This work was supported through a cooperative agreement between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the US Department of Defense (DOD), by the National Institute for Allergy and Infectious Diseases (NIAID), and National Institutes of Health (NIH; grant Y01 AI2642-12). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The US Military HIV Research Program is jointly planned and funded by the DOD and NIAID/NIH by an interagency agreement. This manuscript was approved for publication by the Walter Reed Army Institute of Research. The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the US Army or DOD or the NIH. NR 15 TC 4 Z9 4 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 15 PY 2013 VL 208 IS 8 BP 1250 EP 1254 DI 10.1093/infdis/jit349 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 223TJ UT WOS:000324832800008 PM 23922366 ER PT J AU Je, Y Jeon, JY Giovannucci, EL Meyerhardt, JA AF Je, Youjin Jeon, Justin Y. Giovannucci, Edward L. Meyerhardt, Jeffrey A. TI Association between physical activity and mortality in colorectal cancer: A meta-analysis of prospective cohort studies SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE physical activity; exercise; colon; rectum; cancer; mortality ID III COLON-CANCER; BODY-MASS INDEX; INSULIN SENSITIVITY; STAGE-II; SURVIVAL; IMPACT; INTERVENTION; RECURRENCE; DIAGNOSIS; LEVEL AB Several prospective cohort studies have examined the association between prediagnosis and/or postdiagnosis physical activity (PA) on colorectal cancer outcomes and reported conflicting results. To quantitatively assess this association, we have conducted a meta-analysis of prospective studies. Databases and reference lists of relevant studies were searched using MEDLINE and EMBASE up to January 2013. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models. For this meta-analysis, a total of seven prospective cohort studies were included. The analysis included 5,299 patients for prediagnosis PA and 6,348 patients for postdiagnosis PA, followed up over a period ranging from 3.8 to 11.9 years. The analyses showed that patients who participated in any amount of PA before diagnosis had a RR of 0.75 (95% CI: 0.65-0.87, p < 0.001) for colorectal cancer-specific mortality compared to patients who did not participate in any PA. Those who participated in high PA before diagnosis (vs. low PA) had a RR of 0.70 (95% CI: 0.56-0.87, p = 0.002). Similarly, patients who participated in any PA after diagnosis had a RR of 0.74 (95% CI: 0.58-0.95, p = 0.02) for colorectal cancer-specific mortality compared to patients who did not participate in any PA. Those who participated in high PA after diagnosis (vs. low PA) had a RR of 0.65 (95% CI: 0.47-0.92, p = 0.01). Similar inverse associations of prediagnosis or postdiagnosis PA were found for all-cause mortality. In conclusion, both prediagnosis and postdiagnosis PA were associated with reduced colorectal cancer-specific mortality and all-cause mortality. What's new? Everyone knows exercise is good for you, and it's been shown that physical activity reduces the risk of developing colorectal cancer. A new study investigated what impact exercise has on colorectal cancer outcomes. The authors included a large sample size from seven prospective cohort studies and compared levels of physical activity before and after diagnosis with mortality from all causes after diagnosis with colorectal cancer. They found that physical activity, undertaken either before or after diagnosis, reduces colon cancer mortality. C1 [Je, Youjin] Kyung Hee Univ, Dept Food & Nutr, Seoul, South Korea. [Jeon, Justin Y.] Yonsei Univ, Dept Sport & Leisure Studies, Seoul 120749, South Korea. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Meyerhardt, Jeffrey A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Jeon, JY (reprint author), Yonsei Univ, Dept Sport & Leisure Studies, 50 Yonsei Ro, Seoul 120749, South Korea. EM jjeon@yonsei.ac.kr FU National Research Foundation of Korea (NRF) [2011-0004892] FX Grant sponsor: National Research Foundation of Korea (NRF); Grant number: 2011-0004892 NR 27 TC 50 Z9 50 U1 2 U2 49 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD OCT 15 PY 2013 VL 133 IS 8 BP 1905 EP 1913 DI 10.1002/ijc.28208 PG 9 WC Oncology SC Oncology GA 198FW UT WOS:000322908600017 PM 23580314 ER PT J AU Setsompop, K Kimmlingen, R Eberlein, E Witzel, T Cohen-Adad, J McNab, JA Keil, B Tisdall, MD Hoecht, P Dietz, P Cauley, SF Tountcheva, V Matschl, V Lenz, VH Heberlein, K Potthast, A Thein, H Van Horn, J Toga, A Schmitt, F Lehne, D Rosen, BR Wedeen, V Wald, LL AF Setsompop, K. Kimmlingen, R. Eberlein, E. Witzel, T. Cohen-Adad, J. McNab, J. A. Keil, B. Tisdall, M. D. Hoecht, P. Dietz, P. Cauley, S. F. Tountcheva, V. Matschl, V. Lenz, V. H. Heberlein, K. Potthast, A. Thein, H. Van Horn, J. Toga, A. Schmitt, F. Lehne, D. Rosen, B. R. Wedeen, V. Wald, L. L. TI Pushing the limits of in vivo diffusion MRI for the Human Connectome Project SO NEUROIMAGE LA English DT Article DE MRI; Structural connectivity; Diffusion imaging; Gradient hardware; HARDI; DSI ID FIBER ORIENTATION DISTRIBUTIONS; Q-BALL RECONSTRUCTION; TO-NOISE RATIO; HUMAN BRAIN; 7 TESLA; SPHERICAL DECONVOLUTION; B-1(+) INHOMOGENEITY; MAGNETIC-FIELDS; RF EXCITATION; 8 CHANNELS AB Perhaps more than any other "-omics" endeavor, the accuracy and level of detail obtained from mapping the major connection pathways in the living human brain with diffusion MRI depend on the capabilities of the imaging technology used. The current tools are remarkable; allowing the formation of an "image" of the water diffusion probability distribution in regions of complex crossing fibers at each of half a million voxels in the brain. Nonetheless our ability to map the connection pathways is limited by the image sensitivity and resolution, and also the contrast and resolution in encoding of the diffusion probability distribution. The goal of our Human Connectome Project (HCP) is to address these limiting factors by re-engineering the scanner from the ground up to optimize the high b-value, high angular resolution diffusion imaging needed for sensitive and accurate mapping of the brain's structural connections. Our efforts were directed based on the relative contributions of each scanner component. The gradient subsection was a major focus since gradient amplitude is central to determining the diffusion contrast, the amount of T-2 signal loss, and the blurring of the water PDF over the course of the diffusion time. By implementing a novel 4-port drive geometry and optimizing size and linearity for the brain, we demonstrate a whole-body sized scanner with G(max) = 300 mT/m on each axis capable of the sustained duty cycle needed for diffusion imaging. The system is capable of slewing the gradient at a rate of 200 T/m/s as needed for the EPI image encoding. In order to enhance the efficiency of the diffusion sequence we implemented a FOV shifting approach to Simultaneous MultiSlice (SMS) EPI capable of unaliasing 3 slices excited simultaneously with a modest g-factor penalty allowing us to diffusion encode whole brain volumes with low TR and TE. Finally we combine the multi-slice approach with a compressive sampling reconstruction to sufficiently undersample q-space to achieve a DSI scan in less than 5 mm. To augment this accelerated imaging approach we developed a 64-channel, tight-fitting brain array coil and show its performance benefit compared to a commercial 32-channel coil at all locations in the brain for these accelerated acquisitions. The technical challenges of developing the over-all system are discussed as well as results from SNR comparisons, ODF metrics and fiber tracking comparisons. The ultra-high gradients yielded substantial and immediate gains in the sensitivity through reduction of TE and improved signal detection and increased efficiency of the DSI or HARDI acquisition, accuracy and resolution of diffusion tractography, as defined by identification of known structure and fiber crossing. Published by Elsevier Inc. C1 [Setsompop, K.; Witzel, T.; Cohen-Adad, J.; McNab, J. A.; Keil, B.; Tisdall, M. D.; Cauley, S. F.; Tountcheva, V.; Rosen, B. R.; Wedeen, V.; Wald, L. L.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,AA Martinos Ctr Biomed Ima, Boston, MA 02115 USA. [Kimmlingen, R.; Eberlein, E.; Hoecht, P.; Dietz, P.; Matschl, V.; Lenz, V. H.; Potthast, A.; Thein, H.; Schmitt, F.; Lehne, D.] Siemens Healthcare, Erlangen, Germany. [Heberlein, K.] Siemens Healthcare, Boston, MA USA. [Van Horn, J.; Toga, A.] Univ Calif Los Angeles, Dept Neurol, Lab Neuro Imaging, Los Angeles, CA 90024 USA. RP Wald, LL (reprint author), MGH AA Martinos Imaging Ctr, Bldg 149 13th St Rm 2301, Charlestown, MA 02129 USA. EM wald@nmr.mgh.harvard.edu RI Setsompop, Kawin/P-1464-2014; Wald, Lawrence/D-4151-2009; Keil, Boris/P-1411-2014; Cauley, Stephen/P-1386-2014; Witzel, Thomas/P-1402-2014 OI Setsompop, Kawin/0000-0003-0455-7634; FU National Institutes of Health [P41EB015896]; NIH Blueprint Initiative for Neuroscience Research grant [U01MH093765]; NIH NIBIB grant [K99/R00EB012107] FX This work acknowledges funding from the National Institutes of Health, NIH Blueprint Initiative for Neuroscience Research grant U01MH093765, National Institutes of Health grant P41EB015896, and NIH NIBIB grant K99/R00EB012107. NR 77 TC 86 Z9 87 U1 3 U2 50 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 15 PY 2013 VL 80 BP 220 EP 233 DI 10.1016/j.neuroimage.2013.05.078 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 191MB UT WOS:000322416000017 PM 23707579 ER PT J AU McNab, JA Edlow, BL Witzel, T Huang, SY Bhat, H Heberlein, K Feiweier, T Liu, KC Keil, B Cohen-Adad, J Tisdall, MD Folkerth, RD Kinney, HC Wald, LL AF McNab, Jennifer A. Edlow, Brian L. Witzel, Thomas Huang, Susie Y. Bhat, Himanshu Heberlein, Keith Feiweier, Thorsten Liu, Kecheng Keil, Boris Cohen-Adad, Julien Tisdall, M. Dylan Folkerth, Rebecca D. Kinney, Hannah C. Wald, Lawrence L. TI The Human Connectome Project and beyond: Initial applications of 300 mT/m gradients SO NEUROIMAGE LA English DT Article DE Human connectome; Diffusion MRI; Tractography; Traumatic coma; Consciousness; Axon diameter; Corpus callosum; In vivo; Postmortem ID AMYOTROPHIC-LATERAL-SCLEROSIS; THALAMIC INTRALAMINAR NUCLEI; AXON DIAMETER DISTRIBUTION; ASCENDING AROUSAL SYSTEM; PLACEBO-CONTROLLED TRIAL; TRAUMATIC BRAIN-INJURY; CORPUS-CALLOSUM; DIFFUSION MRI; HEAD-INJURY; RETICULAR-FORMATION AB The engineering of a 3 T human MRI scanner equipped with 300 mT/m gradients - the strongest gradients ever built for an in vivo human MRI scanner - was a major component of the NIH Blueprint Human Connectome Project (HCP). This effort was motivated by the HCP's goal of mapping, as completely as possible, the macroscopic structural connections of the in vivo healthy, adult human brain using diffusion tractography. Yet, the 300 mT/m gradient system is well suited to many additional types of diffusion measurements. Here, we present three initial applications of the 300 mT/m gradients that fall outside the immediate scope of the HCP. These include: 1) diffusion tractography to study the anatomy of consciousness and the mechanisms of brain recovery following traumatic coma; 2) q-space measurements of axon diameter distributions in the in vivo human brain and 3) postmortem diffusion tractography as an adjunct to standard histopathological analysis. We show that the improved sensitivity and diffusion-resolution provided by the gradients are rapidly enabling human applications of techniques that were previously possible only for in vitro and animal models on small-bore scanners, thereby creating novel opportunities to map the microstructure of the human brain in health and disease. (C) 2013 Elsevier Inc. All rights reserved. C1 [McNab, Jennifer A.] Stanford Univ, RM Lucas Ctr Imaging, Dept Radiol, Stanford, CA 94305 USA. [Edlow, Brian L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Edlow, Brian L.; Witzel, Thomas; Huang, Susie Y.; Keil, Boris; Tisdall, M. Dylan; Wald, Lawrence L.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Bhat, Himanshu; Heberlein, Keith; Liu, Kecheng] Siemens Med Solut USA Inc, Alpharetta, GA USA. [Feiweier, Thorsten] Siemens AG, Healthcare Sect, Erlangen, Germany. [Cohen-Adad, Julien] Ecole Polytech, Dept Elect Engn, Montreal, PQ H3C 3A7, Canada. [Folkerth, Rebecca D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Folkerth, Rebecca D.; Kinney, Hannah C.] Harvard Univ, Sch Med, Dept Pathol, Childrens Hosp Boston, Boston, MA 02115 USA. RP McNab, JA (reprint author), Stanford Univ, RM Lucas Ctr Imaging, Dept Radiol, Stanford, CA 94305 USA. EM mcnabj@stanford.edu RI Keil, Boris/P-1411-2014; Witzel, Thomas/P-1402-2014; Wald, Lawrence/D-4151-2009 FU CIHR Fellowship; NIH Blueprint for Neuroscience Research Grant [U01MH093765]; NIH [NCRR P41RR14075, NIBIB RO1 EB006847, NINDS R25NS065743]; Center for Integration of Medicine and Innovative Technology (Boston, MA) FX This work was funded by: a CIHR Fellowship and an NIH Blueprint for Neuroscience Research Grant: U01MH093765, as well as NIH funding from NCRR P41RR14075, NIBIB RO1 EB006847 and NINDS R25NS065743 and the Center for Integration of Medicine and Innovative Technology (Boston, MA). We are grateful to the patient who volunteered for this study and whose recovery from traumatic coma continues to inspire this work. Thank you to Louis Vinke for assistance with processing postmortem brain specimens. Thank you to Emi Takahashi and Guangping Dai for assistance with acquisition of brainstem-diencephalon postmortem data acquired on the small-bore scanner. NR 78 TC 61 Z9 62 U1 4 U2 47 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 15 PY 2013 VL 80 BP 234 EP 245 DI 10.1016/j.neuroimage.2013.05.074 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 191MB UT WOS:000322416000018 PM 23711537 ER PT J AU Hyle, EP Sax, PE Walensky, RP AF Hyle, Emily P. Sax, Paul E. Walensky, Rochelle P. TI Potential Savings by Reduced CD4 Monitoring in Stable Patients With HIV Receiving Antiretroviral Therapy SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Hyle, Emily P.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Sax, Paul E.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. RP Hyle, EP (reprint author), Massachusetts Gen Hosp, Med Practice Evaluat Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM ehyle@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU NIAID NIH HHS [R37 AI042006, R37 AI42006, T32 AI007433]; PHS HHS [T32 A1007433] NR 5 TC 17 Z9 17 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD OCT 14 PY 2013 VL 173 IS 18 BP 1746 EP 1748 DI 10.1001/jamainternmed.2013.9329 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 268TO UT WOS:000328193600019 PM 23978894 ER PT J AU Seabury, SA Chandra, A Jena, AB AF Seabury, Seth A. Chandra, Amitabh Jena, Anupam B. TI Trends in the Earnings of Male and Female Health Care Professionals in the United States, 1987 to 2010 SO JAMA INTERNAL MEDICINE LA English DT Letter ID PHYSICIANS C1 [Seabury, Seth A.] Univ So Calif, Dept Emergency Med, Los Angeles, CA USA. [Seabury, Seth A.] Univ So Calif, Leonard D Schaeffer Ctr Hlth Policy & Econ, Los Angeles, CA USA. [Chandra, Amitabh] Harvard Univ, Harvard Kennedy Sch Govt, Cambridge, MA 02138 USA. [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM jena@hcp.med.harvard.edu FU NIA NIH HHS [P01 AG19783-02] NR 6 TC 22 Z9 22 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD OCT 14 PY 2013 VL 173 IS 18 BP 1748 EP 1750 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 268TO UT WOS:000328193600021 PM 23999898 ER PT J AU Caverly, TJ Prochazka, AV Stickrath, C AF Caverly, Tanner J. Prochazka, Allan V. Stickrath, Chad TI Do Physicians Have an Obligation to Disclose the Uncertainty About Harms or Just the Harms? Reply SO JAMA INTERNAL MEDICINE LA English DT Letter ID COMPUTED-TOMOGRAPHY; RADIATION-EXPOSURE; CT SCANS; CHILDHOOD; RISK C1 [Caverly, Tanner J.; Prochazka, Allan V.; Stickrath, Chad] Univ Colorado, Div Gen Internal Med, Dept Med, Aurora, CO 80042 USA. [Caverly, Tanner J.; Prochazka, Allan V.; Stickrath, Chad] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Caverly, TJ (reprint author), Univ Colorado, Univ Phys Inc, Div Gen Internal Med, Dept Med,Sch Med, 13199 E Montview Blvd,3rd Floor,Ste 300, Aurora, CO 80042 USA. EM Tanner.Caverly@gmail.com FU PHS HHS [T32HP1006] NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD OCT 14 PY 2013 VL 173 IS 18 BP 1752 EP 1752 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 268TO UT WOS:000328193600024 PM 24126773 ER PT J AU Singh, H Sittig, DF AF Singh, Hardeep Sittig, Dean F. TI Toward Electronic Medical Record Alerts That Consume Less Physician Time Reply SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Singh, Hardeep] Baylor Coll Med, Dept Med, Houston VA Hlth Serv Res & Dev HSR&D, Ctr Excellence,Michael E DeBakey Vet Affairs Med, Houston, TX 77030 USA. [Singh, Hardeep] Sect Hlth Serv Res, Houston, TX USA. [Sittig, Dean F.] Univ Texas Houston, Sch Biomed Informat, Houston, TX USA. [Sittig, Dean F.] Univ Texas Houston, Mem Hermann Ctr Healthcare Qual & Safety, Houston, TX USA. RP Singh, H (reprint author), VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD OCT 14 PY 2013 VL 173 IS 18 BP 1756 EP 1756 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 268TO UT WOS:000328193600031 PM 24126782 ER PT J AU Rochet, N Kahn, RS Niemierko, A Delaney, TF Russell, AH AF Rochet, Nathalie Kahn, Rachel S. Niemierko, Andrzej Delaney, Thomas F. Russell, Anthony H. TI Consolidation whole abdomen irradiation following adjuvant carboplatin-paclitaxel based chemotherapy for advanced uterine epithelial cancer: feasibility, toxicity and outcomes SO RADIATION ONCOLOGY LA English DT Article DE Whole abdomen irradiation; Advanced endometrial cancer; Chemotherapy; Radiotherapy ID GYNECOLOGIC-ONCOLOGY-GROUP; ABDOMINOPELVIC RADIATION-THERAPY; IV ENDOMETRIAL CARCINOMA; ADVANCED OVARIAN-CANCER; ABDOMINAL IRRADIATION; STAGE-III; HIGH-RISK; WEEKLY CISPLATIN; PHASE-I; RADIOTHERAPY AB Background: To evaluate feasibility and preliminary outcomes associated with sequential whole abdomen irradiation (WAI) as consolidative treatment following comprehensive surgery and systemic chemotherapy for advanced endometrial cancer. Methods: We conducted a retrospective analysis of patients treated at our institution from 2000 to 2011. Inclusion criteria were stage III-IV endometrial cancer patients with histological proof of one or more sites of extra-uterine abdomen-confined disease, treated with WAI as part of multimodal therapy. Endpoints were feasibility, acute toxicity, late effects, recurrence-free survival (RFS) and overall survival (OS). Twenty patients were identified. Chemotherapy consisted of 3 to 6 cycles of a platinum-paclitaxel regimen in 18 patients. WAI was delivered using conventional technique to a median total dose of 27.5 Gy. Results: No grade 4 toxicities occurred during chemotherapy or radiotherapy. No radiation dose reduction was necessary. Three patients developed small bowel obstruction, all in the context of recurrent intraperitoneal disease. Kaplan-Meier estimates and 95% confidence intervals for RFS and OS at one year were 63% (38-80%) and 83% (56-94%) and at 3 years 57% (33-76%) and 62% (34-81%), respectively. On univariate Cox analysis, stage IVB and serous papillary (SP) histology were found to be statistically significantly (at the p = 0.05 level) associated with worse RFS and OS. The peritoneal cavity was the most frequent site of initial failure. Conclusions: Consolidative WAI following chemotherapy is feasible and can be performed without interruption with manageable acute and late toxicity. Patients with endometrioid adenocarcinoma, especially stage FIGO III, had favorable outcomes possibly meriting prospective evaluation of the addition of WAI following chemotherapy in selected patients. Patients with SP do poorly and do not routinely benefit from this approach. C1 [Rochet, Nathalie; Niemierko, Andrzej; Delaney, Thomas F.; Russell, Anthony H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Rochet, Nathalie] Heidelberg Univ, Dept Radiat Oncol, D-69120 Heidelberg, Germany. [Kahn, Rachel S.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Rochet, Nathalie] CHU Vaudois, Univ Lausanne Hosp, Dept Radiat Oncol, CH-1011 Lausanne, Switzerland. RP Rochet, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,COX3, Boston, MA 02114 USA. EM Nathalie.Rochet@chuv.ch FU German Society of Radiation Oncology (DEGRO) FX Actual or potential conflicts of interest do not exist. All authors declare that there are no conflicts of interest. NR is financially supported by a scholarship from the German Society of Radiation Oncology (DEGRO) for this project. This study has been presented as a poster during ASTRO's 2012 Annual Meeting in Boston (Abstract #2617). NR 25 TC 1 Z9 1 U1 2 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-717X J9 RADIAT ONCOL JI Radiat. Oncol. PD OCT 14 PY 2013 VL 8 AR 236 DI 10.1186/1748-717X-8-236 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 262JT UT WOS:000327731700001 PM 24125168 ER PT J AU Timmerman, LA Holton, T Yuneva, M Louie, RJ Padro, M Daemen, A Hu, M Chan, DA Ethier, SP van 't Veer, LJ Polyak, K McCormick, F Gray, JW AF Timmerman, Luika A. Holton, Thomas Yuneva, Mariia Louie, Raymond J. Padro, Merce Daemen, Anneleen Hu, Min Chan, Denise A. Ethier, Stephen P. van 't Veer, Laura J. Polyak, Kornelia McCormick, Frank Gray, Joe W. TI Glutamine Sensitivity Analysis Identifies the xCT Antiporter as a Common Triple-Negative Breast Tumor Therapeutic Target SO CANCER CELL LA English DT Article ID CANCER CELL-LINES; X(C)(-) CYSTINE/GLUTAMATE ANTIPORTER; AEROBIC GLYCOLYSIS; L-ASPARAGINASE; DNA-DAMAGE; IN-VITRO; GROWTH; METABOLISM; CYSTINE; GLUTATHIONE AB A handful of tumor-derived cell lines form the mainstay of cancer therapeutic development, yielding drugs with an impact typically measured as months to disease progression. To develop more effective breast cancer therapeutics and more readily understand their clinical impact, we constructed a functional metabolic portrait of 46 independently derived breast cell lines. Our analysis of glutamine uptake and dependence identified a subset of triple-negative samples that are glutamine auxotrophs. Ambient glutamine indirectly supports environmental cystine acquisition via the xCT antiporter, which is expressed on one-third of triple-negative tumors in vivo. xCT inhibition with the clinically approved anti-inflammatory sulfasalazine decreases tumor growth, revealing a therapeutic target in breast tumors of poorest prognosis and a lead compound for rapid, effective drug development. C1 [Timmerman, Luika A.; Louie, Raymond J.; Padro, Merce; Daemen, Anneleen; Chan, Denise A.; van 't Veer, Laura J.; McCormick, Frank] Univ Calif San Francisco, UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94115 USA. [Daemen, Anneleen; van 't Veer, Laura J.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94115 USA. [Louie, Raymond J.; Padro, Merce; Chan, Denise A.] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94115 USA. [Holton, Thomas] San Francisco State Univ, Sch Engn, San Francisco, CA 94115 USA. [Hu, Min] Novartis Inst BioMed Res China, Pudong New Area, Shanghai 201203, Peoples R China. [Yuneva, Mariia] MRC Natl Inst Med Res, Div Physiol & Metab, London NW7 1AA, England. [Ethier, Stephen P.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Polyak, Kornelia] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Gray, Joe W.] Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97239 USA. RP Timmerman, LA (reprint author), Univ Calif San Francisco, UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94115 USA. EM timmerma@cc.ucsf.edu FU National Institutes of Health, National Cancer Institute; Bay Area Breast Cancer SPORE [P50 CA 58207]; Prospect Creek Foundation; Durra Family Fund; Mount Zion Health Fund; Supporting Foundation of the Jewish Community Federation; [U54 CA 112970] FX We thank the UCSF/Gladstone Genome Core for microarray dataset generation; T. Cowan, Stanford Biochemical Genetics Laboratory for HPLC amino acid analysis; R. Higashi, CREAM, University of Louisville, for mass spectrometry; the UCSF Preclinical Therapeutics Core for xenografts; and D. Albertson, T. Tlsty, J. Korkola, and W. Kin law for valuable manuscript critiques. Support was provided by the National Institutes of Health, National Cancer Institute, Bay Area Breast Cancer SPORE (P50 CA 58207), grant U54 CA 112970, the Prospect Creek Foundation, the Durra Family Fund, the Mount Zion Health Fund, and a Supporting Foundation of the Jewish Community Federation. NR 59 TC 78 Z9 79 U1 2 U2 22 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD OCT 14 PY 2013 VL 24 IS 4 BP 450 EP 465 DI 10.1016/j.ccr.2013.08.020 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 241WD UT WOS:000326198500008 PM 24094812 ER PT J AU Turner, EH AF Turner, Erick H. TI How to access and process FDA drug approval packages for use in research SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID CLINICAL-TRIALS; PUBLICATION; INFORMATION; DOCUMENTS; REVIEWS C1 [Turner, Erick H.] Portland VA Med Ctr, Behav Hlth & Neurosci Div, Portland, OR USA. [Turner, Erick H.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Turner, Erick H.] Oregon Hlth & Sci Univ, Dept Pharmacol, Portland, OR 97201 USA. [Turner, Erick H.] Oregon Hlth & Sci Univ, Ctr Eth Hlth Care, Portland, OR 97201 USA. RP Turner, EH (reprint author), Portland VA Med Ctr, Behav Hlth & Neurosci Div, Portland, OR USA. EM turnere@ohsu.edu RI Turner, Erick/A-4848-2008 OI Turner, Erick/0000-0002-3522-3357 NR 25 TC 15 Z9 15 U1 2 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD OCT 14 PY 2013 VL 347 AR f5992 DI 10.1136/bmj.f5992 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 238VR UT WOS:000325980100001 PM 24126858 ER PT J AU Tikkanen, AU Opotowsky, AR Bhatt, AB Landzberg, MJ Rhodes, J AF Tikkanen, Ana Ubeda Opotowsky, Alexander R. Bhatt, Ami B. Landzberg, Michael J. Rhodes, Jonathan TI Physical activity is associated with improved aerobic exercise capacity over time in adults with congenital heart disease SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE Congenital heart disease; Adults; Exercise capacity and physical activity ID QUALITY-OF-LIFE; SOCIETAL DATABASE COMMITTEE; ALL-CAUSE MORTALITY; CARDIAC REHABILITATION; CONSENSUS DEFINITIONS; FONTAN OPERATION; TRIAL; LONG; HOSPITALIZATIONS; EXPERIENCE AB Background: Impaired exercise capacity is common in adults with congenital heart disease (ACHD). This impairment is progressive and is associatedwith increasedmorbidity andmortality. We studied the influence of the frequency of at least moderately strenuous physical activity (PhysAct) on changes in exercise capacity of ACHD patients over time. Methods: We studied ACHD patients >= 21 years old who had repeated maximal (RER >= 1.09) cardiopulmonary exercise tests within 6 to 24 months. On the basis of data extracted from each patient's clinical records, PhysAct frequency was classified as (1) Low: minimal PhysAct, (2) Occasional: moderate PhysAct <2 times/week, or (3) Frequent: moderate PhysAct >= 2 times/week. Results: PhysAct frequency could be classified for 146 patients. Those who participated in frequent exercise tended to have improved pVO(2) (Delta pVO(2) = + 1.63 +/- 2.67 ml/kg/min) compared to those who had low or occasional activity frequency (Delta pVO(2) = + 0.06 +/- 2.13 ml/kg/min, p = 0.003) over a median follow-up of 13.2 months. This differencewas independent of baseline clinical characteristics, time between tests, medication changes, orweight change. Thosewho engaged in frequent PhysActweremore likely to have an increase of pVO(2) of = 1SD between tests as compared with sedentary patients (multivariable OR = 7.4, 95% CI 1.5-35.7). Aerobic exercise capacity also increased for patients who increased activity frequency from baseline to follow-up; 27.3% of those who increased their frequency of moderately strenuous physical activity had a clinically significant (at least+ 1SD) increase in pVO2 compared to only 11% of thosewhomaintained or decreased activity frequency. Conclusions: ACHD patients who engage in frequent physical activity tend to have improved exercise capacity over time. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Tikkanen, Ana Ubeda; Opotowsky, Alexander R.; Landzberg, Michael J.; Rhodes, Jonathan] Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Opotowsky, Alexander R.; Landzberg, Michael J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Bhatt, Ami B.] Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. RP Tikkanen, AU (reprint author), Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM anaubedatikkanen@yahoo.es FU Fundacion Alfonso Martin Escudero; National Institutes of Health [5-T32-HL07604-25]; Dunlevie Fund FX This work was supported by Fundacion Alfonso Martin Escudero (AUT), National Institutes of Health 5-T32-HL07604-25 (ARO) and the Dunlevie Fund (ARO/MJL). NR 35 TC 10 Z9 10 U1 0 U2 15 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD OCT 12 PY 2013 VL 168 IS 5 BP 4685 EP 4691 DI 10.1016/j.ijcard.2013.07.177 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 242EI UT WOS:000326219800022 ER PT J AU Ferreira, E Porter, RM Wehling, N O'Sullivan, RP Liu, FJ Boskey, A Estok, DM Harris, MB Vrahas, MS Evans, CH Wells, JW AF Ferreira, Elisabeth Porter, Ryan M. Wehling, Nathalie O'Sullivan, Regina P. Liu, Fangjun Boskey, Adele Estok, Daniel M. Harris, Mitchell B. Vrahas, Mark S. Evans, Christopher H. Wells, James W. TI Inflammatory Cytokines Induce a Unique Mineralizing Phenotype in Mesenchymal Stem Cells Derived from Human Bone Marrow SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NECROSIS-FACTOR-ALPHA; NONSPECIFIC ALKALINE-PHOSPHATASE; INORGANIC PYROPHOSPHATE; OSTEOBLASTS; DIFFERENTIATION; CALCIFICATION; CARTILAGE; MODEL; INTERLEUKIN-1-BETA; EXPRESSION AB Bone marrow contains mesenchymal stem cells (MSCs) that can differentiate along multiple mesenchymal lineages. In this capacity they are thought to be important in the intrinsic turnover and repair of connective tissues while also serving as a basis for tissue engineering and regenerative medicine. However, little is known of the biological responses of human MSCs to inflammatory conditions. When cultured with IL-1 beta, marrow-derived MSCs from 8 of 10 human subjects deposited copious hydroxyapatite, in which authenticity was confirmed by Fourier transform infrared spectroscopy. Transmission electron microscopy revealed the production of fine needles of hydroxyapatite in conjunction with matrix vesicles. Alkaline phosphatase activity did not increase in response to inflammatory mediators, but PPi production fell, reflecting lower ectonucleotide pyrophosphatase activity in cells and matrix vesicles. Because PPi is the major physiological inhibitor of mineralization, its decline generated permissive conditions for hydroxyapatite formation. This is in contrast to MSCs treated with dexamethasone, where PPi levels did not fall and mineralization was fuelled by a large and rapid increase in alkaline phosphatase activity. Bone sialoprotein was the only osteoblast marker strongly induced by IL-1 beta; thus these cells do not become osteoblasts despite depositing abundant mineral. RT-PCR did not detect transcripts indicative of alternative mesenchymal lineages, including chondrocytes, myoblasts, adipocytes, ligament, tendon, or vascular smooth muscle cells. IL-1 beta phosphorylated multiple MAPKs and activated nuclear factor-kappa B (NF-kappa B). Certain inhibitors of MAPK and PI3K, but not NF-kappa B, prevented mineralization. The findings are of importance to soft tissue mineralization, tissue engineering, and regenerative medicine. C1 [Ferreira, Elisabeth; Porter, Ryan M.; O'Sullivan, Regina P.; Liu, Fangjun; Evans, Christopher H.; Wells, James W.] Beth Israel Deaconess Med Ctr, Ctr Adv Orthopaed Studies, Boston, MA 02215 USA. [Ferreira, Elisabeth; Porter, Ryan M.; Vrahas, Mark S.; Evans, Christopher H.; Wells, James W.] AO Fdn, Collaborat Res Ctr, CH-7270 Davos, Switzerland. [Wehling, Nathalie] Asklepios Stadtklin, Dept Surg, D-83646 Bad Tolz, Germany. [Boskey, Adele] Hosp Special Surg, New York, NY 10021 USA. [Estok, Daniel M.; Harris, Mitchell B.] Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Vrahas, Mark S.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Evans, CH (reprint author), Beth Israel Deaconess Med Ctr, Ctr Adv Orthopaed Studies, RN-115,330 Brookline Ave, Boston, MA 02215 USA. EM cevans@bidmc.harvard.edu RI Wells, James/C-7480-2011; OI Wells, James/0000-0002-9618-6940; Boskey, Adele/0000-0002-6181-2219 FU National Institutes of Health [AR050243]; AO Foundation [S-10-72F]; GENDEF FX This work was supported, in whole or in part, by National Institutes of Health Grant AR050243 (NIAMS). This work was also supported by AO Foundation Grants S-10-72F and GENDEF. NR 36 TC 22 Z9 23 U1 2 U2 10 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 OCT 11 PY 2013 VL 288 IS 41 BP 29494 EP 29505 DI 10.1074/jbc.M113.471268 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 302OT UT WOS:000330615300026 PM 23970554 ER PT J AU Kang, HS Lee, S Lee, SA Park, JK AF Kang, Hong Suk Lee, Seungwoo Lee, Sol-Ah Park, Jung-Ki TI Multi-Level Micro/Nanotexturing by Three-Dimensionally Controlled Photofluidization and its Use in Plasmonic Applications SO ADVANCED MATERIALS LA English DT Article DE micro; nanotexturing; azobenzene; photofluidization; holography; plasmonics ID SURFACE-RELIEF GRATINGS; AZOBENZENE MATERIALS; POLYMER-FILMS; LITHOGRAPHY; ARRAYS; ILLUMINATION C1 [Kang, Hong Suk; Park, Jung-Ki] Korea Adv Inst Sci & Technol, Grad Sch EEWS, Taejon 305701, South Korea. [Lee, Seungwoo] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02215 USA. [Lee, Seungwoo] Harvard Univ, Wyss Inst Biol Inspired Engn, Harvard Med Sch, Boston, MA 02215 USA. [Lee, Seungwoo; Lee, Sol-Ah; Park, Jung-Ki] Korea Adv Inst Sci & Technol, Dept Chem & Biomol Engn, Taejon 305701, South Korea. RP Lee, S (reprint author), Harvard Univ, Dana Farber Canc Inst, Boston, MA 02215 USA. EM seungwoo.lee@wyss.harvard.edu; jungpark@kaist.ac.kr RI Park, Jung-Ki/C-1966-2011; Lee, Seungwoo/E-9350-2012 FU Basic Science Research Program through the National Research Foundation of Korea (NRF); Ministry of Education, Science and Technology [NRF-2012R1A1A2042558]; WCU program (EEWS) at KAIST [R-31-2008-000-1005-0] FX H. S. K and S. L. equally contributed to this work. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (code# NRF-2012R1A1A2042558), and WCU program (EEWS) at KAIST (code# R-31-2008-000-1005-0). NR 34 TC 17 Z9 17 U1 4 U2 43 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 0935-9648 EI 1521-4095 J9 ADV MATER JI Adv. Mater. PD OCT 11 PY 2013 VL 25 IS 38 BP 5490 EP 5497 DI 10.1002/adma.201301715 PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 262RY UT WOS:000327756500011 PM 23857634 ER PT J AU Grecco, LAC Duarte, NDC de Mendonca, ME Pasini, H Lima, VLCD Franco, RC de Oliveira, LVF de Carvalho, PDC Correa, JCF Collange, NZ Sampaio, LMM Galli, M Fregni, F Oliveira, CS AF Collange Grecco, Luanda Andre Carvalho Duarte, Natalia de Almeida de Mendonca, Mariana Emerenciano Pasini, Hugo Costa de Carvalho Lima, Vania Lucia Franco, Renata Calhes Franco de Oliveira, Luis Vicente Camilo de Carvalho, Paulo de Tarso Ferrari Correa, Joao Carlos Collange, Nelci Zanon Malosa Sampaio, Luciana Maria Galli, Manuela Fregni, Felipe Oliveira, Claudia Santos TI Effect of transcranial direct current stimulation combined with gait and mobility training on functionality in children with cerebral palsy: study protocol for a double-blind randomized controlled clinical trial SO BMC PEDIATRICS LA English DT Article DE Cerebral palsy; Child; Physiotherapy; Cerebral cortex; Electrical stimulation ID BODY-WEIGHT SUPPORT; GROSS MOTOR FUNCTION; 6-MINUTE WALK TEST; MAGNETIC STIMULATION; OVERGROUND WALKING; PHYSICAL-ACTIVITY; AEROBIC EXERCISE; REHABILITATION; SYSTEM; WII AB Background: The project proposes three innovative intervention techniques (treadmill training, mobility training with virtual reality and transcranial direct current stimulation that can be safely administered to children with cerebral palsy. The combination of transcranial stimulation and physical therapy resources will provide the training of a specific task with multiple rhythmic repetitions of the phases of the gait cycle, providing rich sensory stimuli with a modified excitability threshold of the primary motor cortex to enhance local synaptic efficacy and potentiate motor learning. Methods/design: A prospective, double-blind, randomized, controlled, analytical, clinical trial will be carried out. Eligible participants will be children with cerebral palsy classified on levels I, II and III of the Gross Motor Function Classification System between four and ten years of age. The participants will be randomly allocated to four groups: 1) gait training on a treadmill with placebo transcranial stimulation; 2) gait training on a treadmill with active transcranial stimulation; 3) mobility training with virtual reality and placebo transcranial stimulation; 4) mobility training with virtual reality and active transcranial stimulation. Transcranial direct current stimulation will be applied with the anodal electrode positioned in the region of the dominant hemisphere over C3, corresponding to the primary motor cortex, and the cathode positioned in the supraorbital region contralateral to the anode. A 1 mA current will be applied for 20 minutes. Treadmill training and mobility training with virtual reality will be performed in 30-minute sessions five times a week for two weeks (total of 10 sessions). Evaluations will be performed on four occasions: one week prior to the intervention; one week following the intervention; one month after the end of the intervention; and 3 months after the end of the intervention. The evaluations will involve three-dimensional gait analysis, analysis of cortex excitability (motor threshold and motor evoked potential), Six-Minute Walk Test, Timed Up-and-Go Test, Pediatric Evaluation Disability Inventory, Gross Motor Function Measure, Berg Balance Scale, stabilometry, maximum respiratory pressure and an effort test. Discussion: This paper offers a detailed description of a prospective, double-blind, randomized, controlled, analytical, clinical trial aimed at demonstrating the effect combining transcranial stimulation with treadmill and mobility training on functionality and primary cortex excitability in children with Cerebral Palsy classified on Gross Motor Function Classification System levels I, II and III. The results will be published and will contribute to evidence regarding the use of treadmill training on this population. C1 [Collange Grecco, Luanda Andre; Carvalho Duarte, Natalia de Almeida; Pasini, Hugo; Franco, Renata Calhes; Franco de Oliveira, Luis Vicente; Camilo de Carvalho, Paulo de Tarso; Ferrari Correa, Joao Carlos; Malosa Sampaio, Luciana Maria; Oliveira, Claudia Santos] Univ Nove Julho UNINOVE, Masters & Doctoral Programs Rehabil Sci, Sao Paulo, Brazil. [de Mendonca, Mariana Emerenciano] Univ Sao Paulo, Inst Psychol, Doctoral Program, Sao Paulo, Brazil. [Costa de Carvalho Lima, Vania Lucia] Univ Fed Sao Paulo, Masters & Doctoral Programs Commun Disordes Speec, Sao Paulo, Brazil. [Collange, Nelci Zanon] Univ Sao Paulo, Sao Paulo, Brazil. [Collange, Nelci Zanon] Fed Pediat Neurosurg Ctr CENEPE, Sao Paulo, Brazil. [Galli, Manuela] Politecn Milan, Dipartimento Bioingn, I-20133 Milan, Italy. [Fregni, Felipe] Spaulding Rehabil Hosp, Lab Neuromodulat, Boston, MA USA. [Fregni, Felipe] Spaulding Rehabil Hosp, Ctr Clin Res Learning, Dept Phys Med & Rehabil, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Grecco, LAC (reprint author), Univ Nove Julho UNINOVE, Masters & Doctoral Programs Rehabil Sci, Sao Paulo, Brazil. EM luandacollange@hotmail.com RI Oliveira, Luis/K-8838-2013; Oliveira, Claudia/H-2328-2013; Sampaio, Luciana Maria/H-9429-2016; Grecco , Luanda/N-5075-2015; Duarte, Natalia/K-5260-2016; Moura, Renata/R-5974-2016; de Carvalho, Paulo de Tarso/G-5333-2011 OI Oliveira, Luis/0000-0002-3852-9415; Sampaio, Luciana Maria/0000-0002-0110-7710; Duarte, Natalia/0000-0003-1486-1330; Moura, Renata/0000-0002-4727-2375; de Carvalho, Paulo de Tarso/0000-0001-9624-4103 FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) FX This protocol study received funding from the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq). NR 82 TC 10 Z9 11 U1 1 U2 27 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2431 J9 BMC PEDIATR JI BMC Pediatr. PD OCT 11 PY 2013 VL 13 AR 168 DI 10.1186/1471-2431-13-168 PG 11 WC Pediatrics SC Pediatrics GA 258YJ UT WOS:000327494300001 PM 24112817 ER PT J AU Shuvaev, VV Han, JY Tliba, S Arguiri, E Christofidou-Solomidou, M Ramirez, SH Dykstra, H Persidsky, Y Atochin, DN Huang, PL Muzykantov, VR AF Shuvaev, Vladimir V. Han, Jingyan Tliba, Samira Arguiri, Evguenia Christofidou-Solomidou, Melpo Ramirez, Servio H. Dykstra, Holly Persidsky, Yuri Atochin, Dmitriy N. Huang, Paul L. Muzykantov, Vladimir R. TI Anti-Inflammatory Effect of Targeted Delivery of SOD to Endothelium: Mechanism, Synergism with NO Donors and Protective Effects In Vitro and In Vivo SO PLOS ONE LA English DT Article ID NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; ALLEVIATES OXIDATIVE STRESS; CELL-ADHESION MOLECULE-1; OXIDASE-DERIVED ROS; SUPEROXIDE-DISMUTASE; NITRIC-OXIDE; INDUCED APOPTOSIS; CATALASE; ACTIVATION AB Pro-inflammatory activation of vascular endothelium is implicated in pathogenesis of severe conditions including stroke, infarction and sepsis. We have recently reported that superoxide dismutase (SOD) conjugated with antibodies (Ab/SOD) that provide targeted delivery into endothelial endosomes mitigates inflammatory endothelial activation by cytokines and agonists of Toll-like receptors (TLR). The goal of this study was to appraise potential utility and define the mechanism of this effect. Ab/SOD, but not non-targeted SOD injected in mice alleviated endotoxin-induced leukocyte adhesion in the cerebral vasculature and protected brain from ischemia-reperfusion injury. Transfection of endothelial cells with SOD, but not catalase inhibited NF kappa B signaling and expression of Vascular Cell Adhesion Molecule-1 induced by both cytokines and TLR agonists. These results affirmed that Ab/SOD-quenched superoxide anion produced by endothelial cells in response to proinflammatory agents mediates NF kappa B activation. Furthermore, Ab/SOD potentiates anti-inflammatory effect of NO donors in endothelial cells in vitro, as well as in the endotoxin-challenged mice. These results demonstrate the central role of intracellular superoxide as a mediator of pro-inflammatory activation of endothelium and support the notion of utility of targeted interception of this signaling pathway for management of acute vascular inflammation. C1 [Shuvaev, Vladimir V.; Han, Jingyan; Tliba, Samira; Muzykantov, Vladimir R.] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA. [Shuvaev, Vladimir V.; Han, Jingyan; Tliba, Samira; Muzykantov, Vladimir R.] Univ Penn, Inst Translat Med & Therapeut, Ctr Translat Targeted Therapeut & Nanomed, Philadelphia, PA 19104 USA. [Arguiri, Evguenia; Christofidou-Solomidou, Melpo] Univ Penn, Dept Med, Pulm Allergy & Crit Care Div, Philadelphia, PA 19104 USA. [Ramirez, Servio H.; Dykstra, Holly; Persidsky, Yuri] Temple Univ, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19122 USA. [Atochin, Dmitriy N.; Huang, Paul L.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Atochin, Dmitriy N.; Huang, Paul L.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Atochin, Dmitriy N.; Huang, Paul L.] Harvard Univ, Sch Med, Boston, MA USA. RP Muzykantov, VR (reprint author), Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA. EM muzykant@mail.med.upenn.edu RI Ramirez, Servio/F-8277-2014; Shuvaev, Vladimir/O-1719-2014; Atochin, Dmitriy/Q-3150-2016 FU National Institutes of Health [RO1 HL073940] FX This work was supported by the National Institutes of Health [Grant RO1 HL073940] (to V.R.M.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 12 Z9 13 U1 2 U2 12 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 OCT 11 PY 2013 VL 8 IS 10 AR e77002 DI 10.1371/journal.pone.0077002 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 236SL UT WOS:000325819400093 PM 24146950 ER PT J AU Yousuf, MA Zhou, XH Mukherjee, S Chintakuntlawar, AV Lee, JY Ramke, M Chodosh, J Rajaiya, J AF Yousuf, Mohammad A. Zhou, Xiaohong Mukherjee, Santanu Chintakuntlawar, Ashish V. Lee, Jeong Yoon Ramke, Mirja Chodosh, James Rajaiya, Jaya TI Caveolin-1 Associated Adenovirus Entry into Human Corneal Cells SO PLOS ONE LA English DT Article ID MOUTH-DISEASE VIRUS; MEDIATED ENDOCYTOSIS; LIPID RAFTS; CD46-UTILIZING ADENOVIRUSES; MEMBRANE CHOLESTEROL; ALPHA(V) INTEGRINS; TYPE-19 INFECTION; GENE FAMILY; EARLY STEPS; HOST-CELLS AB The cellular entry of viruses represents a critical area of study, not only for viral tropism, but also because viral entry dictates the nature of the immune response elicited upon infection. Epidemic keratoconjunctivitis (EKC), caused by viruses within human adenovirus species D (HAdV-D), is a severe, ocular surface infection associated with corneal inflammation. Clathrin-mediated endocytosis has previously been shown to play a critical role in entry of other HAdV species into many host cell types. However, HAdV-D endocytosis into corneal cells has not been extensively studied. Herein, we show an essential role for cholesterol rich, lipid raft microdomains and caveolin-1, in the entry of HAdV-D37 into primary human corneal fibroblasts. Cholesterol depletion using methyl-beta-cyclodextrin (M beta CD) profoundly reduced viral infection. When replenished with soluble cholesterol, the effect of M beta CD was reversed, allowing productive viral infection. HAdV-D37 DNA was identified in caveolin-1 rich endosomal fractions after infection. Src kinase activity was also increased in caveolin-1 rich endosomal fractions after infection, and Src phosphorylation and CXCL1 induction were both decreased in caveolin-1-/-mice corneas compared to wild type mice. siRNA knock down of caveolin-1 in corneal cells reduced chemokine induction upon viral infection, and caveolin-1-/-mouse corneas showed reduced cellular entry of HAdV-D37. As a control, HAdV-C2, a non-corneal pathogen, appeared to utilize the caveolar pathway for entry into A549 cells, but failed to infect corneal cells entirely, indicating virus and cell specific tropism. Immuno-electron microscopy confirmed the presence of caveolin-1 in HAdV-D37-containing vesicles during the earliest stages of viral entry. Collectively, these experiments indicate for the first time that HAdV-D37 uses a lipid raft mediated caveolin-1 associated pathway for entry into corneal cells, and connects the processes of viral entry with downstream proinflammatory cell signaling. C1 [Yousuf, Mohammad A.; Zhou, Xiaohong; Mukherjee, Santanu; Chintakuntlawar, Ashish V.; Lee, Jeong Yoon; Ramke, Mirja; Chodosh, James; Rajaiya, Jaya] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Rajaiya, J (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. EM jaya_rajaiya@meei.harvard.edu FU national Institutes of Health (NIH) [EY013124, EY021558, EY014104]; Research to Prevent Blindness Senior Scientific Investigator Award; Falk Foundation; Massachusetts Lions Eye Research Fund FX This work was supported by national Institutes of Health (NIH) grants EY013124, EY021558, and EY014104, a Research to Prevent Blindness Senior Scientific Investigator Award (JC), the Falk Foundation, and the Massachusetts Lions Eye Research Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 99 TC 10 Z9 11 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 OCT 11 PY 2013 VL 8 IS 10 AR UNSP e77462 DI 10.1371/journal.pone.0077462 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 236SL UT WOS:000325819400119 PM 24147000 ER PT J AU Dickerson, BC Wolk, DA AF Dickerson, Bradford C. Wolk, David A. CA Alzheimers Dis Neuroimaging Initia TI Biomarker-based prediction of progression in MCI: comparison of AD signature and hippocampal volume with spinal fluid amyloid-beta and tau SO FRONTIERS IN AGING NEUROSCIENCE LA English DT Article DE Alzheimer's disease; MRI; biomarkers; mild cognitive impairment; CSF biomarkers ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; CSF BIOMARKERS; CEREBROSPINAL-FLUID; CORTICAL SIGNATURE; PROSPECTIVE COHORT; MRI; DEMENTIA; ASSOCIATION; DIAGNOSIS AB Objective: New diagnostic criteria for mild cognitive impairment (MCI) due to Alzheimers disease (AD) have been developed using biomarkers aiming to establish whether the clinical syndrome is likely due to underlying AD. We investigated the utility of magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers in predicting progression from amnesic MCI to dementia, testing the hypotheses that (1) markers of amyloid and neurodegeneration provide distinct and complementary prognostic information over different time intervals, and that (2) evidence of neurodegeneration in amyloid-negative MCI individuals would be useful prognostically. Methods: Data were obtained from the ADNI-1 (Alzheimers Disease Neuroimaging Initiative Phase 1) database on all individuals with a baseline diagnosis of MCI, baseline MRI and CSF data, and at least one follow-up visit. MRI data were processed using a published set of a priori regions of interest to derive a measure known as the AD signature, as well as hippocampal volume. The CSF biomarkers amyloid-beta, total tau, and phospho tau were also examined. We performed logistic regression analyses to identify the best baseline biomarker predictors of progression to dementia over 1 or 3 years, and Cox regression models to test the utility of these markers for predicting time-to-dementia. Results: For prediction of dementia in MCI, the AD signature cortical thickness biomarker performed better than hippocampal volume. Although CSF tau measures were better than CSF amyloid-beta at predicting dementia within 1 year, the AD signature was better than all CSF measures at prediction over this relatively short-term interval. CSF amyloid-beta was superior to tau and AD signature at predicting dementia over 3 years. When CSF amyloid-beta was dichotomized using previously published cutoff values and treated as a categorical variable, a multivariate stepwise Cox regression model indicated that both the AD signature MRI marker and the categorical CSF amyloid-beta marker were useful in predicting time-to-event diagnosis of AD dementia. Conclusion: In amnesic MCI, short-term (1 year) prognosis of progression to dementia relates strongly to baseline markers of neurodegeneration, with the AD signature MRI biomarker of cortical thickness performing the best among MRI and CSF markers studied here. Longer-term (3 year) prognosis in these individuals was better predicted by a marker indicative of brain amyloid. Prediction of time-to-event in a survival model was predicted by the combination of these biomarkers. These results provide further support for emerging models of the temporal relationship of pathophysiologic events in AD and demonstrate the utility of these biomarkers at the prodromal stage of the illness. C1 [Dickerson, Bradford C.] Massachusetts Gen Hosp, Frontotemporal Dementia Unit, Boston, MA 02129 USA. [Dickerson, Bradford C.] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02129 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Wolk, David A.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Wolk, David A.] Univ Penn, Alzheimers Dis Core Ctr, Philadelphia, PA 19104 USA. [Wolk, David A.] Univ Penn, Penn Memory Ctr, Philadelphia, PA 19104 USA. RP Dickerson, BC (reprint author), Massachusetts Gen Hosp, Frontotemporal Dementia Unit, 149 13th St,Suite 2691, Boston, MA 02129 USA. EM bradd@nmr.mgh.harvard.edu FU Alzheimer's Disease Neuroimaging Initiative (ADNI; National Institutes of Health) [U01 AG024904]; 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; NIH [P30 AG010129, K01 AG030514]; Dana Foundation; NIA [P50-AG005134, P30AG010124]; Alzheimer's Association FX Data collection and sharing for this project was funded by the Alzheimers 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 Alzheimers Disease Cooperative Study at the University of California, 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. This research was also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation. This analysis was also supported by grants from the NIA P50-AG005134, P30AG010124, and the Alzheimers Association. We thank Michael Brickhouse for his assistance in data management and analysis. NR 31 TC 31 Z9 33 U1 2 U2 26 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1663-4365 J9 FRONT AGING NEUROSCI JI Front. Aging Neurosci. PD OCT 11 PY 2013 VL 5 AR UNSP 55 DI 10.3389/fnagi.2013.00055 PG 9 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 232WY UT WOS:000325526400001 PM 24130528 ER PT J AU Bauer, DE Kamran, SC Lessard, S Xu, J Fujiwara, Y Lin, C Shao, Z Canver, MC Smith, EC Pinello, L Sabo, PJ Vierstra, J Voit, RA Yuan, GC Porteus, MH Stamatoyannopoulos, JA Lettre, G Orkin, SH AF Bauer, Daniel E. Kamran, Sophia C. Lessard, Samuel Xu, Jian Fujiwara, Yuko Lin, Carrie Shao, Zhen Canver, Matthew C. Smith, Elenoe C. Pinello, Luca Sabo, Peter J. Vierstra, Jeff Voit, Richard A. Yuan, Guo-Cheng Porteus, Matthew H. Stamatoyannopoulos, John A. Lettre, Guillaume Orkin, Stuart H. TI An Erythroid Enhancer of BCL11A Subject to Genetic Variation Determines Fetal Hemoglobin Level SO SCIENCE LA English DT Article ID GENOME-WIDE ASSOCIATION; SICKLE-CELL-DISEASE; HAPLOTYPE FUSION PCR; LYMPHOID DEVELOPMENT; COMMON DISEASE; GLOBIN; DNA; DISSECTION; EXPRESSION; DYNAMICS AB Genome-wide association studies (GWASs) have ascertained numerous trait-associated common genetic variants, frequently localized to regulatory DNA. We found that common genetic variation at BCL11A associated with fetal hemoglobin (HbF) level lies in noncoding sequences decorated by an erythroid enhancer chromatin signature. Fine-mapping uncovers a motif-disrupting common variant associated with reduced transcription factor (TF) binding, modestly diminished BCL11A expression, and elevated HbF. The surrounding sequences function in vivo as a developmental stage-specific, lineage-restricted enhancer. Genome engineering reveals the enhancer is required in erythroid but not B-lymphoid cells for BCL11A expression. These findings illustrate how GWASs may expose functional variants of modest impact within causal elements essential for appropriate gene expression. We propose the GWAS-marked BCL11A enhancer represents an attractive target for therapeutic genome engineering for the beta-hemoglobinopathies. C1 [Bauer, Daniel E.; Xu, Jian; Fujiwara, Yuko; Lin, Carrie; Shao, Zhen; Smith, Elenoe C.; Orkin, Stuart H.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Bauer, Daniel E.; Orkin, Stuart H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Bauer, Daniel E.; Kamran, Sophia C.; Xu, Jian; Canver, Matthew C.; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kamran, Sophia C.; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Lessard, Samuel; Lettre, Guillaume] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Lessard, Samuel; Lettre, Guillaume] Univ Montreal, Montreal, PQ H1T 1C8, Canada. [Pinello, Luca; Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Sabo, Peter J.; Vierstra, Jeff; Stamatoyannopoulos, John A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Sabo, Peter J.; Vierstra, Jeff; Stamatoyannopoulos, John A.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Voit, Richard A.; Porteus, Matthew H.] Stanford Univ, Dept Pediat, Palo Alto, CA 94304 USA. [Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu OI Kamran, Sophia/0000-0001-9283-6515 FU Doris Duke Charitable Foundation [2009089]; Canadian Institute of Health Research [123382]; Amon Carter Foundation; Hyundai Hope on Wheels; NIH [U54HG004594, U54HG007010, R01HL032259, P01HL032262, P30DK049216]; Lucille Packard Foundation; National Institute of Diabetes and Digestive and Kidney Diseases Career Development [K08DK093705] FX We thank A. Woo, A. Cantor, M. Kowalczyk, S. Burns, J. Wright, J. Snow, J. Trowbridge, and members of the Orkin laboratory-particularly C. Peng, P. Das, G. Guo, M. Kerenyi, and E. Baena-for discussions. C. Guo and F. Alt provided the pre-B cell line; A. He and W. Pu provided the pWHERE lacZ reporter construct; C. Currie and M. Nguyen provided technical assistance; D. Bates and T. Kutyavin provided expertise with sequence analysis; R. Sandstrom provided help with data management; G. Losyev and J. Daley provided aid with flow cytometry; and J. Desimini provided graphical assistance. L. Yan at EpigenDx (Hopkinton, Massachusetts) conducted the custom pyrosequencing reactions. This work was funded by grants from the Doris Duke Charitable Foundation (2009089) and Canadian Institute of Health Research (123382) to G. L.; Amon Carter Foundation, Hyundai Hope on Wheels, NIH, Lucille Packard Foundation to M. H. P.; NIH grants U54HG004594 and U54HG007010 to J. A. S.; and NIH R01HL032259, P01HL032262, and P30DK049216 (Center of Excellence in Molecular Hematology) to S. H. O. D. E. B. is supported by National Institute of Diabetes and Digestive and Kidney Diseases Career Development Award K08DK093705. D. E. B., J. X., and S. H. O. are inventors on a patent application related to this work, filed by Boston Children's Hospital. The CSSCD samples with DNA and associated phenotype information are available from the National Heart, Lung, and Blood Institute to researchers that have appropriate institutional review board approval to use the materials. NR 37 TC 161 Z9 163 U1 9 U2 50 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD OCT 11 PY 2013 VL 342 IS 6155 BP 253 EP 257 DI 10.1126/science.1242088 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 232EV UT WOS:000325475200047 PM 24115442 ER PT J AU Haddad, RI AF Haddad, Robert I. TI How to Incorporate New Tyrosine Kinase Inhibitors in the Treatment of Patients With Medullary Thyroid Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CABOZANTINIB; TRIAL C1 [Haddad, Robert I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Haddad, Robert I.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Haddad, RI (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 9 TC 3 Z9 4 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 10 PY 2013 VL 31 IS 29 BP 3618 EP 3620 DI 10.1200/JCO.2013.51.5098 PG 3 WC Oncology SC Oncology GA 301NT UT WOS:000330539700004 PM 24002516 ER PT J AU Elisei, R Schlumberger, MJ Muller, SP Schoffski, P Brose, MS Shah, MH Licitra, L Jarzab, B Medvedev, V Kreissl, MC Niederle, B Cohen, EEW Wirth, LJ Ali, H Hessel, C Yaron, Y Ball, D Nelkin, B Sherman, SI AF Elisei, Rossella Schlumberger, Martin J. Mueller, Stefan P. Schoffski, Patrick Brose, Marcia S. Shah, Manisha H. Licitra, Lisa Jarzab, Barbara Medvedev, Viktor Kreissl, Michael C. Niederle, Bruno Cohen, Ezra E. W. Wirth, Lori J. Ali, Haythem Hessel, Colin Yaron, Yifah Ball, Douglas Nelkin, Barry Sherman, Steven I. TI Cabozantinib in Progressive Medullary Thyroid Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CARCINOEMBRYONIC ANTIGEN LEVELS; ENDOTHELIAL GROWTH-FACTOR; RET PROTOONCOGENE; PHASE-II; SOMATIC MUTATIONS; SERUM CALCITONIN; KINASE INHIBITOR; DOUBLING-TIMES; FOLLOW-UP; CARCINOMA AB Purpose Cabozantinib, a tyrosine kinase inhibitor (TKI) of hepatocyte growth factor receptor (MET), vascular endothelial growth factor receptor 2, and rearranged during transfection (RET), demonstrated clinical activity in patients with medullary thyroid cancer (MTC) in phase I. Patients and Methods We conducted a double-blind, phase III trial comparing cabozantinib with placebo in 330 patients with documented radiographic progression of metastatic MTC. Patients were randomly assigned (2: 1) to cabozantinib (140 mg per day) or placebo. The primary end point was progression-free survival (PFS). Additional outcome measures included tumor response rate, overall survival, and safety. Results The estimated median PFS was 11.2 months for cabozantinib versus 4.0 months for placebo (hazard ratio, 0.28; 95% CI, 0.19 to 0.40; P < .001). Prolonged PFS with cabozantinib was observed across all subgroups including by age, prior TKI treatment, and RET mutation status (hereditary or sporadic). Response rate was 28% for cabozantinib and 0% for placebo; responses were seen regardless of RET mutation status. Kaplan-Meier estimates of patients alive and progression-free at 1 year are 47.3% for cabozantinib and 7.2% for placebo. Common cabozantinib-associated adverse events included diarrhea, palmar-plantar erythrodysesthesia, decreased weight and appetite, nausea, and fatigue and resulted in dose reductions in 79% and holds in 65% of patients. Adverse events led to treatment discontinuation in 16% of cabozantinib-treated patients and in 8% of placebo-treated patients. Conclusion Cabozantinib (140 mg per day) achieved a statistically significant improvement of PFS in patients with progressive metastatic MTC and represents an important new treatment option for patients with this rare disease. This dose of cabozantinib was associated with significant but manageable toxicity. C1 [Elisei, Rossella] Univ Pisa, I-56124 Pisa, Italy. [Licitra, Lisa] Ist Nazl Tumori, Fdn Ist Ricovero & Cura Carattere Sci, I-20133 Milan, Italy. [Schlumberger, Martin J.] Univ Paris 11, Inst Gustave Roussy, Villejuif, France. [Mueller, Stefan P.] Univ Klinikum Essen, Essen, Germany. [Kreissl, Michael C.] Univ Klinikum Wurzburg, Wurzburg, Germany. [Schoffski, Patrick] Katholieke Univ Leuven Hosp, Louvain, Belgium. [Brose, Marcia S.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Shah, Manisha H.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Jarzab, Barbara] Inst Marii Sklodowskiej Curie Oddzial Gliwicach, Ctr Onkol, Gliwice, Poland. [Medvedev, Viktor] Russian Acad Med Sci, Med Radiol Res Ctr, Obninsk, Russia. [Niederle, Bruno] Med Univ Wien, Vienna, Austria. [Cohen, Ezra E. W.] Univ Chicago, Chicago, IL 60637 USA. [Wirth, Lori J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ali, Haythem] Henry Ford Hlth Syst, Detroit, MI USA. [Hessel, Colin; Yaron, Yifah] Exelixis, San Francisco, CA USA. [Ball, Douglas; Nelkin, Barry] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Sherman, Steven I.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Elisei, R (reprint author), Univ Pisa, Dept Endocrinol, Via Paradisa 2, I-56124 Pisa, Italy. EM rossella.elisei@med.unipi.it RI Licitra, Lisa/C-6271-2017; OI Licitra, Lisa/0000-0003-0623-4118; Sherman, Steven/0000-0002-3079-5153; Niederle, Bruno/0000-0001-8107-4068 FU Exelixis; Eisai; Bayer; Douglas Ball FX Rossella Elisei, Exelixis; Martin J. Schlumberger, Exelixis; Marcia S. Brose, Exelixis; Manisha H. Shah, Exelixis, Eisai, Bayer; Viktor Medvedev, Exelixis; Douglas Ball, Exelixis NR 37 TC 234 Z9 243 U1 1 U2 26 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 10 PY 2013 VL 31 IS 29 BP 3639 EP + DI 10.1200/JCO.2012.48.4659 PG 9 WC Oncology SC Oncology GA 301NT UT WOS:000330539700008 PM 24002501 ER PT J AU San-Miguel, JF Richardson, PG Gunther, A Sezer, O Siegel, D Blade, J LeBlanc, R Sutherland, H Sopala, M Mishra, KK Mu, S Bourquelot, PM Mateos, MV Anderson, KC AF San-Miguel, Jesus F. Richardson, Paul G. Guenther, Andreas Sezer, Orhan Siegel, David Blade, Joan LeBlanc, Richard Sutherland, Heather Sopala, Monika Mishra, Kaushal K. Mu, Song Bourquelot, Priscille M. Victoria Mateos, Maria Anderson, Kenneth C. TI Phase Ib Study of Panobinostat and Bortezomib in Relapsed or Relapsed and Refractory Multiple Myeloma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LENALIDOMIDE PLUS DEXAMETHASONE; INHIBITOR PANOBINOSTAT; DEACETYLASE INHIBITORS; WORKING GROUP; SINGLE-AGENT; COMBINATION; PREDNISONE; PROTEASOME; MELPHALAN; CRITERIA AB Purpose Despite advancements, prognosis for patients with relapsed/refractory multiple myeloma (MM) is poor, and novel therapies are needed. Panobinostat is a potent deacetylase inhibitor that elicits synergistic effects on MM cells in combination with bortezomib. This phase Ib study sought to determine the maximum-tolerated dose (MTD) of panobinostat plus bortezomib in patients with relapsed or relapsed and refractory MM. Patients and Methods In the dose-escalation phase (n = 47), panobinostat was administered orally thrice weekly every week in combination with bortezomib (21-day cycles). After MTD determination, patients were evaluated in an expansion phase (n = 15) that incorporated a 1-week treatment holiday of panobinostat, with dexamethasone added in cycle 2. Additional assessments included safety, pharmacokinetics, and efficacy per International Myeloma Working Group criteria. Results The MTD was established at panobinostat 20 mg plus bortezomib 1.3 mg/m(2). Grade 3 or 4 adverse events (AEs) included thrombocytopenia (85.1%), neutropenia (63.8%), and asthenia (29.8%) in the escalation phase, and thrombocytopenia (66.7%), neutropenia (46.7%), and fatigue (20.0%) in the expansion phase. At MTD in the escalation phase, eight patients (47.1%) discontinued therapy as a result of AEs, whereas five patients (33.3%) discontinued treatment in the expansion phase. Expansion phase patients demonstrated greater median treatment duration. Overall response rate (ORR) was 73.3% in the expansion phase and 52.9% at the escalation phase MTD. Among bortezomib-refractory patients, the ORR was 26.3%, and 42.1% of patients had minimal response. Conclusion The MTD of panobinostat plus bortezomib was determined and demonstrated activity in patients with relapsed or relapsed/refractory MM, including bortezomib-refractory patients. A phase II/III clinical trial program (Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma [PANORAMA]) has been initiated. C1 [San-Miguel, Jesus F.; Victoria Mateos, Maria] Univ Salamanca, Spanish Natl Res Council, Inst Bil Mol Barcelona, Inst Invest Biomed Salamanca,Hosp Univ Salamanca, E-37008 Salamanca, Spain. [Blade, Joan] Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain. [Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Siegel, David] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Mishra, Kaushal K.; Mu, Song] Novartis Pharmaceut, E Hanover, NJ USA. [Guenther, Andreas] Univ Kiel, Kiel, Germany. [Sezer, Orhan] Charite, D-13353 Berlin, Germany. [LeBlanc, Richard] Hop Maison Neuve Rosemont, Montreal, PQ H1T 2M4, Canada. [Sutherland, Heather] Vancouver Gen Hosp, Vancouver, BC, Canada. [Sopala, Monika; Bourquelot, Priscille M.] Novartis Pharma AG, Basel, Switzerland. RP San-Miguel, JF (reprint author), Hosp Univ Salamanca, Paseo San Vicente 58-182, Salamanca 37007, Spain. EM sanmigiz@usal.es OI Sopala, Monika/0000-0001-9587-7953; SAN MIGUEL, JESUS/0000-0002-9183-4857 FU Novartis; Janssen-Ortho FX Andreas Gunther, Novartis; Orhan Sezer, Janssen-Ortho, Novartis; Joan Blade, Janssen-Ortho NR 35 TC 72 Z9 73 U1 0 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 10 PY 2013 VL 31 IS 29 BP 3696 EP + DI 10.1200/JCO.2012.46.7068 PG 15 WC Oncology SC Oncology GA 301NT UT WOS:000330539700018 PM 24019544 ER PT J AU Di Saverio, S Coccolini, F Galati, M Smerieri, N Biffl, WL Ansaloni, L Tugnoli, G Velmahos, GC Sartelli, M Bendinelli, C Fraga, GP Kelly, MD Moore, FA Mandala, V Mandala, S Masetti, M Jovine, E Pinna, AD Peitzman, AB Leppaniemi, A Sugarbaker, PH Van Goor, H Moore, EE Jeekel, J Catena, F AF Di Saverio, Salomone Coccolini, Federico Galati, Marica Smerieri, Nazareno Biffl, Walter L. Ansaloni, Luca Tugnoli, Gregorio Velmahos, George C. Sartelli, Massimo Bendinelli, Cino Fraga, Gustavo Pereira Kelly, Michael D. Moore, Frederick A. Mandala, Vincenzo Mandala, Stefano Masetti, Michele Jovine, Elio Pinna, Antonio D. Peitzman, Andrew B. Leppaniemi, Ari Sugarbaker, Paul H. Van Goor, Harry Moore, Ernest E. Jeekel, Johannes Catena, Fausto TI Bologna guidelines for diagnosis and management of adhesive small bowel obstruction (ASBO): 2013 update of the evidence-based guidelines from the world society of emergency surgery ASBO working group SO WORLD JOURNAL OF EMERGENCY SURGERY LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; UNSUCCESSFUL CONSERVATIVE TREATMENT; POSTOPERATIVE ABDOMINAL ADHESIONS; SOLUBLE CONTRAST-MEDIUM; LAPAROSCOPIC ADHESIOLYSIS; BIORESORBABLE MEMBRANE; INTESTINAL-OBSTRUCTION; CLINICAL-TRIAL; ANIMAL-MODEL; HELICAL CT AB Background: In 2013 Guidelines on diagnosis and management of ASBO have been revised and updated by the WSES Working Group on ASBO to develop current evidence-based algorithms and focus indications and safety of conservative treatment, timing of surgery and indications for laparoscopy. Recommendations: In absence of signs of strangulation and history of persistent vomiting or combined CT-scan signs (free fluid, mesenteric edema, small-bowel feces sign, devascularization) patients with partial ASBO can be managed safely with NOM and tube decompression should be attempted. These patients are good candidates for Water-Soluble-Contrast-Medium (WSCM) with both diagnostic and therapeutic purposes. The radiologic appearance of WSCM in the colon within 24 hours from administration predicts resolution. WSCM maybe administered either orally or via NGT both immediately at admission or after failed conservative treatment for 48 hours. The use of WSCM is safe and reduces need for surgery, time to resolution and hospital stay. NOM, in absence of signs of strangulation or peritonitis, can be prolonged up to 72 hours. After 72 hours of NOM without resolution, surgery is recommended. Patients treated non-operatively have shorter hospital stay, but higher recurrence rate and shorter time to readmission, although the risk of new surgically treated episodes of ASBO is unchanged. Risk factors for recurrences are age <40 years and matted adhesions. WSCM does not decrease recurrence rates or recurrences needing surgery. Open surgery is often used for strangulating ASBO as well as after failed conservative management. In selected patients and with appropriate skills, laparoscopic approach is advisable using open access technique. Access in left upper quadrant or left flank is the safest and only completely obstructing adhesions should be identified and lysed with cold scissors. Laparoscopic adhesiolysis should be attempted preferably if first episode of SBO and/or anticipated single band. A low threshold for open conversion should be maintained. Peritoneal adhesions should be prevented. Hyaluronic acid-carboxycellulose membrane and icodextrin decrease incidence of adhesions. Icodextrin may reduce the risk of re-obstruction. HA cannot reduce need of surgery. Adhesions quantification and scoring maybe useful for achieving standardized assessment of adhesions severity and for further research in diagnosis and treatment of ASBO. C1 [Di Saverio, Salomone; Galati, Marica; Smerieri, Nazareno; Tugnoli, Gregorio; Masetti, Michele; Jovine, Elio] Maggiore Hosp Trauma Ctr, Emergency & Trauma Surg Unit, Dept Emergency, Bologna, Italy. [Di Saverio, Salomone; Galati, Marica; Smerieri, Nazareno; Tugnoli, Gregorio; Masetti, Michele; Jovine, Elio] Maggiore Hosp Trauma Ctr, Emergency & Trauma Surg Unit, Dept Surg, Bologna, Italy. [Pinna, Antonio D.; Catena, Fausto] S Orsola Malpighi Univ Hosp, Dept Gen & Multivisceral Transplant Surg, Emergency Surg Unit, Bologna, Italy. [Kelly, Michael D.] NHS Trust, Frenchay Hosp, Dept Surg, Upper GI Unit, Bristol, Avon, England. [Biffl, Walter L.; Moore, Ernest E.] Univ Colorado Hlth Sci Denver, Denver Hlth Med Ctr, Denver Hlth, Dept Surg, Denver, CO 80204 USA. [Coccolini, Federico; Ansaloni, Luca] Osped Riuniti Bergamo, I-24100 Bergamo, Italy. [Mandala, Vincenzo; Mandala, Stefano] Associated Hosp Villa Sofia Cervello, Dept Gen & Emergency Surg, Palermo, Italy. [Velmahos, George C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. [Sartelli, Massimo] Macerata Hosp, Dept Surg, I-62100 Macerata, Italy. [Sugarbaker, Paul H.] Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA. [Van Goor, Harry] Radboud Univ Nijmegen, Med Ctr, Dept Surg, NL-6525 ED Nijmegen, Netherlands. [Moore, Frederick A.] Univ Florida, Dept Surg, Gainesville, FL 32610 USA. [Jeekel, Johannes] Erasmus MC, Dept Surg, Rotterdam, Netherlands. [Bendinelli, Cino] John Hunter Hosp, Dept Surg, Newcastle, NSW 2310, Australia. [Bendinelli, Cino] Univ Newcastle, Locke Bag Hunter Reg Maile Ctr 1, Newcastle, NSW 2310, Australia. [Catena, Fausto] Maggiore Hosp Parma, Dept Emergency & Trauma Surg, Parma, Italy. [Leppaniemi, Ari] Univ Helsinki, Meilahti Hosp, Dept Abdominal Surg, FIN-00029 Helsinki, Hus, Finland. [Peitzman, Andrew B.] Univ Pittsburgh Phys, Div Gen Surg, Pittsburgh, PA 15213 USA. [Fraga, Gustavo Pereira] Univ Estadual Campinas, Div Trauma Surg, Campinas, SP, Brazil. RP Catena, F (reprint author), S Orsola Malpighi Univ Hosp, Dept Gen & Multivisceral Transplant Surg, Emergency Surg Unit, Bologna, Italy. EM faustocatena@gmail.com RI Goor, H./H-8035-2014; OI Ansaloni, Luca/0000-0001-6427-0307; Di Saverio, Salomone/0000-0001-5685-5022 NR 102 TC 30 Z9 31 U1 3 U2 22 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1749-7922 J9 WORLD J EMERG SURG JI World J. Emerg. Surg. PD OCT 10 PY 2013 VL 8 AR 42 DI 10.1186/1749-7922-8-42 PG 14 WC Emergency Medicine; Surgery SC Emergency Medicine; Surgery GA 262FY UT WOS:000327720900001 PM 24112637 ER PT J AU Kulkarni-Datar, K Orsulic, S Foster, R Rueda, BR AF Kulkarni-Datar, Kashmira Orsulic, Sandra Foster, Rosemary Rueda, Bo R. TI Ovarian tumor initiating cell populations persist following paclitaxel and carboplatin chemotherapy treatment in vivo SO CANCER LETTERS LA English DT Article DE Ovarian cancer tumor initiating cells; Sca-1 cells; CD133 cells ID CANCER STEM-CELLS; GYNECOLOGIC-ONCOLOGY-GROUP; CISPLATIN TREATMENT; PROSTATE-CANCER; CARCINOMA; SURVIVAL; CD133; CHEMORESISTANCE; RESISTANCE; EXPRESSION AB Development of recurrent platinum resistant disease following chemotherapy presents a challenge in managing ovarian cancer. Using tumors derived from genetically defined mouse ovarian cancer cells, we investigated the stem cell properties of residual cells post-chemotherapy. Utilizing CD133 and Sca-1 as markers of candidate tumor initiating cells (TIC), we determined that the relative levels of CD133(+) and sca-1(+) cells were unaltered following chemotherapy. CD133(+) and Sca-1(+) cells exhibited increased stem cell-related gene expression, were enriched in G(0)/G(1)-early S phase and exhibited increased tumor initiating capacity, giving rise to heterogeneous tumors. Our findings suggest that residual TICs may contribute to recurrent disease. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Kulkarni-Datar, Kashmira; Foster, Rosemary; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Kulkarni-Datar, Kashmira; Foster, Rosemary; Rueda, Bo R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Orsulic, Sandra] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Rueda, BR (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Vincent Obstet & Gynecol, Boston, MA 02114 USA. EM brueda@partners.org FU Advanced Medical Research Foundation; Vincent Memorial Research Funds FX This research was funded in part by grants from the Advanced Medical Research Foundation (BRR) and the Vincent Memorial Research Funds (BRR). NR 63 TC 7 Z9 7 U1 0 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 EI 1872-7980 J9 CANCER LETT JI Cancer Lett. PD OCT 10 PY 2013 VL 339 IS 2 BP 237 EP 246 DI 10.1016/j.canlet.2013.06.014 PG 10 WC Oncology SC Oncology GA 229YO UT WOS:000325304000010 PM 23791886 ER PT J AU Andrews, JR Lawn, SD Dowdy, DW Walensky, RP AF Andrews, Jason R. Lawn, Stephen D. Dowdy, David W. Walensky, Rochelle P. TI Challenges in Evaluating the Cost-effectiveness of New Diagnostic Tests for HIV-Associated Tuberculosis SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE tuberculosis; HIV; diagnostics; cost-effectiveness; health policy ID NEGATIVE PULMONARY TUBERCULOSIS; ANTIRETROVIRAL THERAPY; SOUTH-AFRICA; HEALTH IMPACT; CARE; POINT; LIPOARABINOMANNAN; CULTURE; ADULTS; URINE AB With an emerging array of rapid diagnostic tests for tuberculosis, cost-effectiveness analyses are needed to inform scale-up in various populations and settings. Human immunodeficiency virus (HIV)-associated tuberculosis poses unique challenges in estimating and interpreting the cost-effectiveness of novel diagnostic tools. First, gains in sensitivity and specificity do not directly correlate with impact on clinical outcomes. Second, the cost-effectiveness of implementing tuberculosis diagnostics in HIV-infected populations is heavily influenced by downstream costs of HIV care. As a result, tuberculosis diagnostics may appear less cost-effective in this population than among HIV-uninfected individuals, raising important ethical and policy questions about the design and interpretation of cost-effectiveness analyses in this setting. Third, conventional cost-effectiveness benchmarks may be inadequate for making decisions about whether to adopt new diagnostics. If we are to appropriately deploy novel diagnostics for tuberculosis to people living with HIV in resource-constrained settings, these challenges in measuring cost-effectiveness must be more widely recognized and addressed. C1 [Andrews, Jason R.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Andrews, Jason R.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Dept Med, Boston, MA 02114 USA. [Lawn, Stephen D.] Univ Cape Town, Fac Hlth Sci, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, ZA-7700 Rondebosch, South Africa. [Lawn, Stephen D.] Univ London London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Clin Res, London WC1E 7HT, England. [Dowdy, David W.] Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Dowdy, David W.] Johns Hopkins Univ, Ctr TB Res, Baltimore, MD USA. RP Andrews, JR (reprint author), Massachusetts Gen Hosp, Med Practice Evaluat Ctr, 9th Floor,50 Staniford St, Boston, MA 02114 USA. EM jandrews6@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X; Andrews, Jason/0000-0002-5967-251X FU National Institute of Allergy and Infectious Diseases [R01 AI093269, R01 AI058736, T32AI007433]; Harvard Global Health Institute; Wellcome Trust, London, UK FX This work was supported by the National Institute of Allergy and Infectious Diseases (grant numbers R01 AI093269, R01 AI058736, and T32AI007433) and the Harvard Global Health Institute. S. D. L. is funded by the Wellcome Trust, London, UK. NR 46 TC 7 Z9 7 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 10 PY 2013 VL 57 IS 7 BP 1021 EP 1026 DI 10.1093/cid/cit412 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 239LX UT WOS:000326027400015 PM 23788239 ER PT J AU Goodson, JM Tavares, M Wang, XS Niederman, R Cugini, M Hasturk, H Barake, R Alsmadi, O Al-Mutawa, S Ariga, J Soparkar, P Behbehani, J Behbehani, K AF Goodson, J. Max Tavares, Mary Wang, Xiaoshan Niederman, Richard Cugini, Maryann Hasturk, Hatice Barake, Roula Alsmadi, Osama Al-Mutawa, Sabiha Ariga, Jitendra Soparkar, Pramod Behbehani, Jawad Behbehani, Kazem TI Obesity and Dental Decay: Inference on the Role of Dietary Sugar SO PLOS ONE LA English DT Article ID NUTRITIONAL-STATUS; KUWAITI CHILDREN; US CHILDREN; CARIES; ASSOCIATION; SCHOOLCHILDREN; ADOLESCENTS; OVERWEIGHT; RATES AB Objective: To evaluate the relationship of children's obesity and dental decay. Methods: We measured parameters related to obesity and dental decay in 8,275 4th and 5th grade Kuwaiti children (average age=11.36 years) in a cross-sectional study. First to determine body weight, height, age for computation of BMI. Second, to determine numbers of teeth, numbers of fillings and numbers of untreated decayed teeth to determine extent and severity of dental disease. From these measurements, we computed measures of dental decay in children from four body weight categories; obese, overweight, normal healthy weight and underweight children. Results: The percentage of children with decayed or filled teeth varied inversely with the body weight category. The percentage of decayed or filled teeth decreased from 15.61% (n=193) in underweight children, to 13.03% (n=4,094) in normal healthy weight children, to 9.73% (n=1,786) in overweight children to 7.87% (n=2,202) in obese children. Differences between all groups were statistically significant. Male children in this population had more dental decay than female children but the reduction of tooth decay as a function of BMI was greater in male children. Conclusions: The finding of an inverse obesity-dental decay relationship contradicts the obesity-sugar and the obesity-dental decay relationship hypotheses. Sugar is well recognized as necessary and sufficient for dental decay. Sugar is also hypothesized to be a leading co-factor in obesity. If the later hypothesis is true, one would expect dental decay to increase with obesity. This was not found. The reasons for this inverse relationship are not currently clear. C1 [Goodson, J. Max; Tavares, Mary; Wang, Xiaoshan; Niederman, Richard; Cugini, Maryann; Hasturk, Hatice; Soparkar, Pramod] Forsyth Inst, Cambridge, MA USA. [Barake, Roula] Dasman Diabet Inst, Nutr Serv, Kuwait, Kuwait. [Alsmadi, Osama; Behbehani, Kazem] Dasman Diabet Inst, Kuwait, Kuwait. [Al-Mutawa, Sabiha] Minist Hlth, Kuwait, Kuwait. [Ariga, Jitendra] Minist Hlth, Sch Oral Hlth Program, Kuwait, Kuwait. [Behbehani, Jawad] Kuwait Univ, Fac Dent, Kuwait, Kuwait. RP Goodson, JM (reprint author), Forsyth Inst, Cambridge, MA USA. EM mgoodson@forsyth.org RI Wang, Xiaoshan/D-6292-2014 OI Wang, Xiaoshan/0000-0002-6760-5456 FU Dasman Institute, Kuwait FX This work was funded by the Dasman Institute, Kuwait. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 20 TC 6 Z9 6 U1 2 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 10 PY 2013 VL 8 IS 10 AR e74461 DI 10.1371/journal.pone.0074461 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 236QM UT WOS:000325814200001 PM 24130667 ER PT J AU Elmariah, SB Lerner, EA AF Elmariah, Sarina B. Lerner, Ethan A. TI The Missing Link between Itch and Inflammation in Atopic Dermatitis SO CELL LA English DT Editorial Material ID THYMIC STROMAL LYMPHOPOIETIN; SKIN; MICE AB Atopic dermatitis is a common skin disease with high morbidity and is associated with severe itch and chronic skin inflammation. In this issue of Cell, Wilson et al. demonstrate that epithelial cells communicate directly with cutaneous sensory neurons via a cytokine to induce itch. C1 [Elmariah, Sarina B.; Lerner, Ethan A.] Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. [Elmariah, Sarina B.; Lerner, Ethan A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Elmariah, SB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. EM sbelmariah@partners.org FU NIAMS NIH HHS [R01AR057744, R01 AR057744] NR 11 TC 7 Z9 7 U1 0 U2 25 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD OCT 10 PY 2013 VL 155 IS 2 BP 267 EP 269 DI 10.1016/j.cell.2013.09.038 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 235LH UT WOS:000325719800002 PM 24120126 ER PT J AU Israelsen, WJ Dayton, TL Davidson, SM Fiske, BP Hosios, AM Bellinger, G Li, J Yu, YM Sasaki, M Horner, JW Burga, LN Xie, JX Jurczak, MJ DePinho, RA Clish, CB Jacks, T Kibbey, RG Wulf, GM Di Vizio, D Mills, GB Cantley, LC Vander Heiden, MG AF Israelsen, William J. Dayton, Talya L. Davidson, Shawn M. Fiske, Brian P. Hosios, Aaron M. Bellinger, Gary Li, Jie Yu, Yimin Sasaki, Mika Horner, James W. Burga, Laura N. Xie, Jianxin Jurczak, Michael J. DePinho, Ronald A. Clish, Clary B. Jacks, Tyler Kibbey, Richard G. Wulf, Gerburg M. Di Vizio, Dolores Mills, Gordon B. Cantley, Lewis C. Vander Heiden, Matthew G. TI PKM2 Isoform-Specific Deletion Reveals a Differential Requirement for Pyruvate Kinase in Tumor Cells SO CELL LA English DT Article ID GENE-TRANSCRIPTION; HNRNP PROTEINS; M2 ISOFORM; CANCER; GROWTH; METABOLISM; PROMOTES; ACTIVATION; MICE; PHOSPHORYLATION AB The pyruvate kinase M2 isoform (PKM2) is expressed in cancer and plays a role in regulating anabolic metabolism. To determine whether PKM2 is required for tumor formation or growth, we generated mice with a conditional allele that abolishes PKM2 expression without disrupting PKM1 expression. PKM2 deletion accelerated mammary tumor formation in a Brca1-loss-driven model of breast cancer. PKM2 null tumors displayed heterogeneous PKM1 expression, with PKM1 found in nonproliferating tumor cells and no detectable pyruvate kinase expression in proliferating cells. This suggests that PKM2 is not necessary for tumor cell proliferation and implies that the inactive state of PKM2 is associated with the proliferating cell population within tumors, whereas nonproliferating tumor cells require active pyruvate kinase. Consistent with these findings, variable PKM2 expression and heterozygous PKM2 mutations are found in human tumors. These data suggest that regulation of PKM2 activity supports the different metabolic requirements of proliferating and nonproliferating tumor cells. C1 [Israelsen, William J.; Dayton, Talya L.; Davidson, Shawn M.; Fiske, Brian P.; Hosios, Aaron M.; Bellinger, Gary; Yu, Yimin; Jacks, Tyler; Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Li, Jie; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. [Sasaki, Mika; Burga, Laura N.; Wulf, Gerburg M.; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Dept Med, Boston, MA 02115 USA. [Horner, James W.; DePinho, Ronald A.; Vander Heiden, Matthew G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Xie, Jianxin] Cell Signaling Technol, Danvers, MA 01923 USA. [Jurczak, Michael J.; Kibbey, Richard G.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Clish, Clary B.] Broad Inst, Cambridge, MA 02142 USA. [Kibbey, Richard G.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. [Di Vizio, Dolores] Cedars Sinai Med Ctr, Div Canc Biol & Therapeut, Los Angeles, CA 90048 USA. [Di Vizio, Dolores] Boston Childrens Hosp, Urol Dis Res Ctr, Boston, MA 02115 USA. [Di Vizio, Dolores] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Vander Heiden, MG (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM mvh@mit.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIH [R01CA168653, 5P01CA117969, P30CA147882, 5P30CA14051, 5K08CA136983, DK059635, R01DK092606, R00CA131472, R01GM056203]; ADA grant [7-12-BS-09]; Belfer Foundation; Smith Family Foundation; Burroughs Wellcome Fund; Damon Runyon Cancer Research Foundation; Stern family FX We thank Chu-Xia Deng for sharing the BRCA1 mouse model; Luigi Terracciano and Luigi Tornillo for providing the multitissue TMA; and Cynthia Clower, Sarah-Maria Fendt, Andrea J. Howell, Vivian M. Liu, Sophia Lunt, Katherine R. Mattaini, Benjamin A. Olenchock, and Kerry Pierce for technical assistance. Eric L. Bell provided advice and reagents. Denise G. Crowley, Michael Brown, and Kathleen S. Cormier assisted with histology. This work was supported, in part, by NIH grants R01CA168653, 5P01CA117969, P30CA147882, 5P30CA14051, 5K08CA136983, DK059635, R01DK092606, R00CA131472, and R01GM056203 and ADA grant 7-12-BS-09. R.A.D. and J.W.H. acknowledge support from the Belfer Foundation. M.G.V.H. acknowledges additional support from the Smith Family Foundation, the Burroughs Wellcome Fund, the Damon Runyon Cancer Research Foundation, and the Stern family. C.B.C. is a shareholder in Agios Pharmaceuticals. M.G.V.H. is a shareholder and Scientific Advisory Board member at Agios Pharmaceuticals. L.C.C. owns equity in and receives compensation from Agios Pharmaceuticals and serves on the Board of Directors and Scientific Advisory Board. NR 43 TC 109 Z9 113 U1 4 U2 58 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD OCT 10 PY 2013 VL 155 IS 2 BP 397 EP 409 DI 10.1016/j.cell.2013.09.025 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 235LH UT WOS:000325719800016 PM 24120138 ER PT J AU Brennan, CW Verhaak, RGW McKenna, A Campos, B Noushmehr, H Salama, SR Zheng, SY Chakravarty, D Sanborn, JZ Berman, SH Beroukhim, R Bernard, B Wu, CJ Genovese, G Shmulevich, I Barnholtz-Sloan, J Zou, LH Vegesna, R Shukla, SA Ciriello, G Yung, WK Zhang, W Sougnez, C Mikkelsen, T Aldape, K Bigner, DD Van Meir, EG Prados, M Sloan, A Black, KL Eschbacher, J Finocchiaro, G Friedman, W Andrews, DW Guha, A Iacocca, M O'Neill, BP Foltz, G Myers, J Weisenberger, DJ Penny, R Kucherlapati, R Perou, CM Hayes, DN Gibbs, R Marra, M Mills, GB Lander, E Spellman, P Wilson, R Sander, C Weinstein, J Meyerson, M Gabriel, S Laird, PW Haussler, D Getz, G Chin, L AF Brennan, Cameron W. Verhaak, Roel G. W. McKenna, Aaron Campos, Benito Noushmehr, Houtan Salama, Sofie R. Zheng, Siyuan Chakravarty, Debyani Sanborn, J. Zachary Berman, Samuel H. Beroukhim, Rameen Bernard, Brady Wu, Chang-Jiun Genovese, Giannicola Shmulevich, Ilya Barnholtz-Sloan, Jill Zou, Lihua Vegesna, Rahulsimham Shukla, Sachet A. Ciriello, Giovanni Yung, W. K. Zhang, Wei Sougnez, Carrie Mikkelsen, Tom Aldape, Kenneth Bigner, Darell D. Van Meir, Erwin G. Prados, Michael Sloan, Andrew Black, Keith L. Eschbacher, Jennifer Finocchiaro, Gaetano Friedman, William Andrews, David W. Guha, Abhijit Iacocca, Mary O'Neill, Brian P. Foltz, Greg Myers, Jerome Weisenberger, Daniel J. Penny, Robert Kucherlapati, Raju Perou, Charles M. Hayes, D. Neil Gibbs, Richard Marra, Marco Mills, Gordon B. Lander, Eric Spellman, Paul Wilson, Richard Sander, Chris Weinstein, John Meyerson, Matthew Gabriel, Stacey Laird, Peter W. Haussler, David Getz, Gad Chin, Lynda CA TCGA Res Network TI The Somatic Genomic Landscape of Glioblastoma SO CELL LA English DT Article ID COPY-NUMBER ALTERATION; DRIVER MUTATIONS; HUMAN CANCERS; GRADE GLIOMA; TUMORS; EGFR; EXPRESSION; MELANOMA; PATHWAYS; SURVIVAL AB We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer. C1 [Brennan, Cameron W.; Chakravarty, Debyani; Berman, Samuel H.] Mem Sloan Kettering Canc Ctr, Brain Tumor Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Brennan, Cameron W.] Weill Cornell Med Ctr, Dept Neurol Surg, Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10065 USA. [Verhaak, Roel G. W.; Zheng, Siyuan; Vegesna, Rahulsimham; Weinstein, John] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [McKenna, Aaron; Beroukhim, Rameen; Zou, Lihua; Sougnez, Carrie; Lander, Eric; Meyerson, Matthew; Gabriel, Stacey; Getz, Gad; Chin, Lynda] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA 02142 USA. [Campos, Benito; Beroukhim, Rameen; Shukla, Sachet A.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Campos, Benito] Univ Heidelberg Hosp, Dept Neurosurg, Div Expt Neurosurg, D-69120 Heidelberg, Germany. [Noushmehr, Houtan; Weisenberger, Daniel J.; Laird, Peter W.] Univ So Calif, Keck Sch Med, Univ Southern Calif Epigenome Ctr, Los Angeles, CA 90033 USA. [Noushmehr, Houtan] Univ Sao Paulo, Fac Med Ribeirao Preto, Ctr Integrat Syst Biol, Dept Genet, BR-14049900 Sao Paulo, Brazil. [Salama, Sofie R.; Sanborn, J. Zachary; Haussler, David] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA. [Salama, Sofie R.; Sanborn, J. Zachary; Haussler, David] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA. [Bernard, Brady; Shmulevich, Ilya] Inst Syst Biol, Seattle, WA 98109 USA. [Verhaak, Roel G. W.; Wu, Chang-Jiun; Genovese, Giannicola; Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. [Barnholtz-Sloan, Jill] Case Western Reserve Univ, Sch Med, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. [Ciriello, Giovanni; Sander, Chris] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA. [Yung, W. K.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Zhang, Wei; Aldape, Kenneth] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Mikkelsen, Tom] Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA. [Mikkelsen, Tom] Henry Ford Hosp, Dept Neurosurg, Detroit, MI 48202 USA. [Bigner, Darell D.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Van Meir, Erwin G.] Emory Univ, Winship Canc Inst, Dept Neurosurg, Atlanta, GA 30322 USA. [Van Meir, Erwin G.] Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Van Meir, Erwin G.] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Prados, Michael] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. [Sloan, Andrew] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Dept Neurosurg, Cleveland, OH 44106 USA. [Black, Keith L.] Cedars Sinai Med Ctr, Dept Neurosurg, Los Angeles, CA 90048 USA. [Eschbacher, Jennifer] St Josephs Hosp, Dept Pathol, Phoenix, AZ 85013 USA. [Finocchiaro, Gaetano] Ist Neurol Besta, Dept Neurooncol, I-20133 Milan, Italy. [Friedman, William] Univ Florida, Dept Neurosurg, Gainesville, FL 32610 USA. [Andrews, David W.] Thomas Jefferson Univ, Dept Neurol Surg, Philadelphia, PA 19107 USA. [Guha, Abhijit] Toronto Western Hosp, Dept Neurosurg, Toronto, ON M5T 2S8, Canada. [Iacocca, Mary] Helen F Graham Canc Ctr, Christiana Care, Dept Pathol, Newark, DE 19713 USA. [O'Neill, Brian P.] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA. [O'Neill, Brian P.] Mayo Clin, Ctr Canc, Rochester, MN 55905 USA. [Foltz, Greg] Swedish Neurosci Inst, Ivy Brain Tumor Ctr, Seattle, WA 98122 USA. [Myers, Jerome] Penrose St Francis Hlth Serv, Dept Pathol, Colorado Springs, CO 80907 USA. [Penny, Robert] Int Genom Consortium, Phoenix, AZ 85004 USA. [Kucherlapati, Raju] Brigham & Womens Hosp, Boston, MA 02215 USA. [Kucherlapati, Raju] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Perou, Charles M.; Hayes, D. Neil] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Gibbs, Richard] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Marra, Marco] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada. [Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. [Spellman, Paul] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA. [Wilson, Richard] Washington Univ, Genome Inst, St Louis, MO 63110 USA. [Haussler, David] Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA. RP Brennan, CW (reprint author), Mem Sloan Kettering Canc Ctr, Brain Tumor Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. EM cbrennan@mskcc.org; lchin@mdanderson.org RI Schumacher, Steven/E-9821-2013; Noushmehr, Houtan/C-9692-2013; Tang, Macy/B-9798-2014; Laird, Peter/G-8683-2012; Jacobsen, Anders/K-1081-2013; Lee, Semin/S-2629-2016; Marra, Marco/B-5987-2008; Miller, Ryan/B-9365-2008; OI Schumacher, Steven/0000-0002-6819-5647; Noushmehr, Houtan/0000-0003-4051-8114; Jacobsen, Anders/0000-0001-6847-4980; Lee, Semin/0000-0002-9015-6046; Miller, Ryan/0000-0002-0096-8762; Van Meir, Erwin G./0000-0003-2444-7707; Chakravarty, Debyani/0000-0001-8629-5732; Brennan, Cameron/0000-0003-4064-8891; Lash, Alex/0000-0003-3787-1590; Pot, David/0000-0002-1480-9826; Fuller, Gregory/0000-0001-9447-2647; Perou, Charles/0000-0001-9827-2247; Gehlenborg, Nils/0000-0003-0327-8297 FU USA National Institutes of Health [U24CA143883, U24CA143858, U24C A143840, U24CA143799, U24CA143835, U24CA143845, U24CA143882, U24 CA143867, U24CA143866]; [U24CA143848]; [U24CA144025]; [U24CA143843]; [U54HG003067]; [U54HG003079]; [U54HG003273]; [U24CA126543]; [U24CA12 6544]; [U24CA126546]; [U24CA126551]; [U24CA126554]; [U24CA126561]; [U24CA 126563]; [U24CA143731] FX The TCGA research network contributed collectively to this study. Biospecimens were provided by the Tissue Source Sites and processed by the Biospecimen Core Resource. Data generation and analyses were performed by the Genome Sequencing Centers, Cancer Genome Characterization Centers, and Genome Data Analysis Centers. All data were released through the Data Coordinating Center. Project activities were coordinated by NCI and NHGRI Project Teams. This work was supported by the following grants from the USA National Institutes of Health: U24CA143883, U24CA143858, U24C A143840, U24CA143799, U24CA143835, U24CA143845, U24CA143882, U24 CA143867, U24CA143866, U24CA143848, U24CA144025, U24CA143843, U54HG003067, U54HG003079, U54HG003273, U24CA126543, U24CA12 6544, U24CA126546, U24CA126551, U24CA126554, U24CA126561, U24CA 126563, and U24CA143731. NR 50 TC 710 Z9 725 U1 31 U2 161 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD OCT 10 PY 2013 VL 155 IS 2 BP 462 EP 477 DI 10.1016/j.cell.2013.09.034 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 235LH UT WOS:000325719800021 PM 24120142 ER PT J AU Avivar-Valderas, A Bobrovnikova-Marjon, E Diehl, JA Bardeesy, N Debnath, J Aguirre-Ghiso, JA AF Avivar-Valderas, A. Bobrovnikova-Marjon, E. Diehl, J. Alan Bardeesy, N. Debnath, J. Aguirre-Ghiso, J. A. TI Regulation of autophagy during ECM detachment is linked to a selective inhibition of mTORC1 by PERK SO ONCOGENE LA English DT Article DE anoikis; breast cancer; unfolded protein response ID ACTIVATED PROTEIN-KINASE; EXTRACELLULAR-MATRIX DETACHMENT; ENDOPLASMIC-RETICULUM KINASE; ANOIKIS RESISTANCE; UPSTREAM KINASE; CELL-GROWTH; STRESS; PHOSPHORYLATION; SUPPRESSION; SURVIVAL AB Adhesion to the extracellular matrix (ECM) is critical for epithelial tissue homeostasis and function. ECM detachment induces metabolic stress and programmed cell death via anoikis. ECM-detached mammary epithelial cells are able to rapidly activate autophagy allowing for survival and an opportunity for re-attachment. However, the mechanisms controlling detachment-induced autophagy remain unclear. Here we uncover that the kinase PERK rapidly promotes autophagy in ECM-detached cells by activating AMP-activated protein kinase (AMPK), resulting in downstream inhibition of mTORC1-p70(S6K) signaling. LKB1 and TSC2, but not TSC1, are required for PERK-mediated inhibition of mammalian target of rapamycinin MCF10A cells and mouse embryo fibroblast cells. Importantly, this pathway shows fast kinetics, is transcription-independent and is exclusively activated during ECM detachment, but not by canonical endoplasmic reticulum stressors. Moreover, enforced PERK or AMPK activation upregulates autophagy and causes luminal filling during acinar morphogenesis by perpetuating a population of surviving autophagic luminal cells that resist anoikis. Hence, we identify a novel pathway in which suspension-activated PERK promotes the activation of LKB1, AMPK and TSC2, leading to the rapid induction of detachment-induced autophagy. We propose that increased autophagy, secondary to persistent PERK and LKB1-AMPK signaling, can robustly protect cells from anoikis and promote luminal filling during early carcinoma progression. C1 [Avivar-Valderas, A.; Aguirre-Ghiso, J. A.] Mt Sinai Sch Med, Tisch Canc Inst, Black Family Stem Cell Inst, Dept Med, New York, NY 10029 USA. [Avivar-Valderas, A.; Aguirre-Ghiso, J. A.] Mt Sinai Sch Med, Tisch Canc Inst, Black Family Stem Cell Inst, Dept Otolaryngol, New York, NY 10029 USA. [Bobrovnikova-Marjon, E.; Diehl, J. Alan] Univ Penn, Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA. [Bobrovnikova-Marjon, E.; Diehl, J. Alan] Univ Penn, Sch Med, Abramson Canc Res Inst, Philadelphia, PA 19104 USA. [Bardeesy, N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Debnath, J.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA. [Debnath, J.] Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. RP Aguirre-Ghiso, JA (reprint author), Mt Sinai Sch Med, Tisch Canc Inst, Black Family Stem Cell Inst, Dept Med, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM julio.aguirre-ghiso@mssm.edu OI Aguirre-Ghiso, Julio/0000-0002-6694-6507 FU NIH-NCI shared resources [5R24CA095823-04]; NSF Major Research Instrumentation grant [DBI-9724504]; NIH [1 S10RR0 9145-01, RO1 CA126792, CA126792-S1, P01 CA104838]; Samuel Waxman Cancer Research Foundation Tumor Dormancy Program; NIH/National Cancer Institute [CA109182, CA163131]; NIEHS [ES017146]; NYSTEM; Leukemia and Lymphoma Scholar FX Confocal laser scanning microscopy was performed at the MSSM-Microscopy Shared Resources Facility, supported with funding from NIH-NCI shared resources grant (5R24CA095823-04), NSF Major Research Instrumentation grant (DBI-9724504) and NIH shared instrumentation grant (1 S10RR0 9145-01). This work is supported by grants from the Samuel Waxman Cancer Research Foundation Tumor Dormancy Program, NIH/National Cancer Institute (CA109182, CA163131), NIEHS (ES017146) and NYSTEM to J. A. A-G, NIH RO1 CA126792, CA126792-S1 (ARRA) to JD, and P01 CA104838 and a Leukemia and Lymphoma Scholar award to JAD. NR 39 TC 38 Z9 38 U1 2 U2 13 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 OCT 10 PY 2013 VL 32 IS 41 BP 4932 EP 4940 DI 10.1038/onc.2012.512 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 235KQ UT WOS:000325717800009 PM 23160380 ER PT J AU Ghoshal, G Chi, LP Barabasi, AL AF Ghoshal, Gourab Chi, Liping Barabasi, Albert-Laszlo TI Uncovering the role of elementary processes in network evolution SO SCIENTIFIC REPORTS LA English DT Article ID GROWING RANDOM NETWORKS; COMPLEX NETWORKS; DEGREE DISTRIBUTIONS; EVOLVING NETWORKS; ROBUSTNESS; INTERNET; GRAPHS; WEB AB The growth and evolution of networks has elicited considerable interest from the scientific community and a number of mechanistic models have been proposed to explain their observed degree distributions. Various microscopic processes have been incorporated in these models, among them, node and edge addition, vertex fitness and the deletion of nodes and edges. The existing models, however, focus on specific combinations of these processes and parameterize them in a way that makes it difficult to elucidate the role of the individual elementary mechanisms. We therefore formulated and solved a model that incorporates the minimal processes governing network evolution. Some contribute to growth such as the formation of connections between existing pair of vertices, while others capture deletion; the removal of a node with its corresponding edges, or the removal of an edge between a pair of vertices. We distinguish between these elementary mechanisms, identifying their specific role on network evolution. C1 [Ghoshal, Gourab; Chi, Liping; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Dept Phys Biol & Comp Sci, Boston, MA 02115 USA. [Ghoshal, Gourab; Barabasi, Albert-Laszlo] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Ghoshal, Gourab; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Chi, Liping] Cent China Normal Univ, Inst Particle Phys, Complex Sci Res Ctr, Wuhan 430079, Peoples R China. RP Ghoshal, G (reprint author), Harvard Univ, Dept Earth & Planetary Sci, 20 Oxford St, Cambridge, MA 02138 USA. EM gghoshal@fas.harvard.edu FU Network Science Collaborative Technology Alliance; US Army Research Laboratory [W911NF-09-2-0053]; Defense Advanced Research Projects Agency [11645021]; Defense Threat Reduction Agency [WMD BRBAA07-J-2-0035] FX We thank C. Song for valuable discussions. This work was supported by the Network Science Collaborative Technology Alliance sponsored by the US Army Research Laboratory under Agreement Number W911NF-09-2-0053; the Defense Advanced Research Projects Agency under Agreement Number 11645021; the Defense Threat Reduction Agency award WMD BRBAA07-J-2-0035; and the generous support of Lockheed Martin. NR 51 TC 8 Z9 10 U1 0 U2 33 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD OCT 10 PY 2013 VL 3 AR 2920 DI 10.1038/srep02920 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 232DH UT WOS:000325469500007 PM 24108146 ER PT J AU Hormoz, S AF Hormoz, Sahand TI Amino acid composition of proteins reduces deleterious impact of mutations SO SCIENTIFIC REPORTS LA English DT Article ID GENETIC-CODE; ESCHERICHIA-COLI; SEQUENCES; EVOLUTION; MODELS; THERMODYNAMICS; POTENTIALS; STABILITY; DESIGN AB The evolutionary origin of amino acid occurrence frequencies in proteins (composition) is not yet fully understood. We suggest that protein composition works alongside the genetic code to minimize impact of mutations on protein structure. First, we propose a novel method for estimating thermodynamic stability of proteins whose sequence is constrained to a fixed composition. Second, we quantify the average deleterious impact of substituting one amino acid with another. Natural proteome compositions are special in at least two ways: 1) Natural compositions do not generate more stable proteins than the average random composition, however, they result in proteins that are less susceptible to damage from mutations. 2) Natural proteome compositions that result in more stable proteins (i.e. those of thermophiles) are also tuned to have a higher tolerance for mutations. This is consistent with the observation that environmental factors selecting for more stable proteins also enhance the deleterious impact of mutations. C1 [Hormoz, Sahand] Univ Calif Santa Barbara, Kavli Inst Theoret Phys, Santa Barbara, CA 93106 USA. [Hormoz, Sahand] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Hormoz, Sahand] Harvard Univ, Kavli Inst Bionano Sci & Technol, Cambridge, MA 02138 USA. [Hormoz, Sahand] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Hormoz, S (reprint author), Univ Calif Santa Barbara, Kavli Inst Theoret Phys, Kohn Hall, Santa Barbara, CA 93106 USA. EM hormoz@kitp.ucsb.edu FU National Science Foundation [NSF PHY11-25915] FX The author is thankful to Michael P. Brenner for stimulating discussions and critical reading of the manuscript, and Eugene Shakhnovich for helpful suggestions. This research was supported in part by the National Science Foundation under Grant No. NSF PHY11-25915. NR 46 TC 13 Z9 13 U1 0 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD OCT 10 PY 2013 VL 3 AR 2919 DI 10.1038/srep02919 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 232DH UT WOS:000325469500006 PM 24108121 ER PT J AU Katz, IT Bassett, IV Wright, AA AF Katz, Ingrid T. Bassett, Ingrid V. Wright, Alexi A. TI PEPFAR in Transition - Implications for HIV Care in South Africa SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material AB With the U.S. government halving the budget for the President's Emergency Plan for AIDS Relief in South Africa by 2017, the country is transitioning to full ownership of its HIV program. Will the move jeopardize the health of 1.7 million South Africans being treated for HIV? This summer marked the 10th anniversary of the creation of the President's Emergency Plan for AIDS Relief (PEPFAR), widely considered the most ambitious and successful global public health program since smallpox eradication. Over the past decade, PEPFAR has funded HIV-AIDS treatment for more than 5 million people in resource-limited settings in sub-Saharan Africa. Now, the U.S. government has reached a turning point in its emergency response and has decided to reduce funding to many of these countries, including South Africa, recipient of the most PEPFAR dollars. In August 2012, the U.S. government announced it would cut South Africa's PEPFAR budget ... C1 [Katz, Ingrid T.] Massachusetts Gen Hosp, Div Womens Hlth, Brigham & Womens Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Katz, Ingrid T.; Bassett, Ingrid V.; Wright, Alexi A.] Harvard Univ, Sch Med, Boston, MA USA. [Bassett, Ingrid V.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Bassett, Ingrid V.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Bassett, Ingrid V.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Wright, Alexi A.] Dana Farber Canc Ctr, Boston, MA USA. RP Katz, IT (reprint author), Massachusetts Gen Hosp, Div Womens Hlth, Brigham & Womens Hosp, Ctr Global Hlth, Boston, MA 02114 USA. FU NIMH NIH HHS [K23 MH097667, R01 MH090326] NR 5 TC 18 Z9 18 U1 0 U2 22 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 10 PY 2013 VL 369 IS 15 BP 1385 EP 1387 DI 10.1056/NEJMp1310982 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 231QE UT WOS:000325431500002 PM 24106930 ER PT J AU Ruschitzka, F Abraham, WT Singh, JP Bax, JJ Borer, JS Brugada, J Dickstein, K Ford, I Gorcsan, J Gras, D Krum, H Sogaard, P Holzmeister, J AF Ruschitzka, Frank Abraham, William T. Singh, Jagmeet P. Bax, Jeroen J. Borer, Jeffrey S. Brugada, Josep Dickstein, Kenneth Ford, Ian Gorcsan, John Gras, Daniel Krum, Henry Sogaard, Peter Holzmeister, Johannes CA EchoCRT Study Grp TI Cardiac-Resynchronization Therapy in Heart Failure with a Narrow QRS Complex SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LEFT-VENTRICULAR DYSSYNCHRONY; LONG-TERM SURVIVAL; MECHANICAL DYSSYNCHRONY; RADIAL STRAIN; TRIAL; ECHOCARDIOGRAPHY; DEFIBRILLATOR; PREVALENCE; ASYNCHRONY; REDUCTION AB BackgroundCardiac-resynchronization therapy (CRT) reduces morbidity and mortality in chronic systolic heart failure with a wide QRS complex. Mechanical dyssynchrony also occurs in patients with a narrow QRS complex, which suggests the potential usefulness of CRT in such patients. MethodsWe conducted a randomized trial involving 115 centers to evaluate the effect of CRT in patients with New York Heart Association class III or IV heart failure, a left ventricular ejection fraction of 35% or less, a QRS duration of less than 130 msec, and echocardiographic evidence of left ventricular dyssynchrony. All patients underwent device implantation and were randomly assigned to have CRT capability turned on or off. The primary efficacy outcome was the composite of death from any cause or first hospitalization for worsening heart failure. ResultsOn March 13, 2013, the study was stopped for futility on the recommendation of the data and safety monitoring board. At study closure, the 809 patients who had undergone randomization had been followed for a mean of 19.4 months. The primary outcome occurred in 116 of 404 patients in the CRT group, as compared with 102 of 405 in the control group (28.7% vs. 25.2%; hazard ratio, 1.20; 95% confidence interval [CI], 0.92 to 1.57; P=0.15). There were 45 deaths in the CRT group and 26 in the control group (11.1% vs. 6.4%; hazard ratio, 1.81; 95% CI, 1.11 to 2.93; P=0.02). ConclusionsIn patients with systolic heart failure and a QRS duration of less than 130 msec, CRT does not reduce the rate of death or hospitalization for heart failure and may increase mortality. (Funded by Biotronik and GE Healthcare; EchoCRT ClinicalTrials.gov number, NCT00683696.) In a randomized trial, patients with heart failure and a QRS duration of less than 130 msec were assigned to cardiac-resynchronization therapy (CRT) or no CRT. There were no significant differences in rates of death from any cause or hospitalization for heart failure. Despite recent advances, heart failure remains a common cause of death and morbidity. According to current guidelines, cardiac-resynchronization therapy (CRT) is indicated for patients receiving stable medical therapy recommended by current guidelines who have moderate-to-severe heart failure, a left ventricular ejection fraction of 35% or less, and a QRS duration of 120 msec or more as assessed electrocardiographically.(1) However, many patients with heart failure have a QRS duration of less than 120 msec,(2) and it is currently not recommended that they receive CRT. Up to 50% of these patients show echocardiographic evidence of ventricular dyssynchrony(3),(4) and hence might benefit ... C1 [Ruschitzka, Frank; Holzmeister, Johannes] Univ Zurich Hosp, Clin Cardiol, CH-8091 Zurich, Switzerland. [Abraham, William T.] Ohio State Univ, Med Ctr, Div Cardiovascular Med, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. [Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA USA. [Bax, Jeroen J.] Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands. [Borer, Jeffrey S.] State Univ New York Downstate Coll Med, Div Cardiovasc Med, New York, NY USA. [Borer, Jeffrey S.] State Univ New York Downstate Coll Med, Howard Gilman & Ron Inst, New York, NY USA. [Borer, Jeffrey S.] State Univ New York Downstate Coll Med, Jean Schiavone Inst, New York, NY USA. [Brugada, Josep] Univ Barcelona, Dept Cardiol, Thorax Inst, Hosp Clin, Barcelona, Spain. [Dickstein, Kenneth] Univ Bergen, Stavanger Univ Hosp, Stavanger, Norway. [Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland. [Gorcsan, John] Univ Pittsburgh, Pittsburgh, PA USA. [Gras, Daniel] Nouvelles Clin Nantaises, Nantes, France. [Krum, Henry] Monash Ctr Cardiovasc Res & Educ Therapeut, Melbourne, Vic, Australia. [Sogaard, Peter] Aalborg Univ, Aalborg, Denmark. RP Holzmeister, J (reprint author), Univ Zurich Hosp, Clin Cardiol, Raemistr 100, CH-8091 Zurich, Switzerland. EM johannes.holzmeister@usz.ch; johannes.holzmeister@usz.ch RI Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; BRUGADA, JOSEP/0000-0002-5662-8302; Ng, G. Andre/0000-0001-5965-0671 FU Biotronik; GE Healthcare FX Supported by Biotronik and GE Healthcare. NR 32 TC 201 Z9 207 U1 5 U2 33 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 10 PY 2013 VL 369 IS 15 BP 1395 EP 1405 DI 10.1056/NEJMoa1306687 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 231QE UT WOS:000325431500007 PM 23998714 ER PT J AU Heller, HM Wu, CC Pierce, VM Kradin, RL AF Heller, Howard M. Wu, Carol C. Pierce, Virginia M. Kradin, Richard L. TI Case 31-2013: A 29-Year-Old Man with Abdominal Pain, Fever, and Weight Loss SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; GASTROINTESTINAL HISTOPLASMOSIS; AIDS; DIAGNOSIS AB A 29-year-old man was seen in an outpatient clinic because of abdominal pain, fever, and weight loss. Testing for HIV antibodies was positive, and the CD4 T-lymphocyte count was 10 per cubic millimeter. Chest imaging revealed tiny nodules in both lungs. Presentation of CaseDr. Nosheen Reza (Medicine): A 29-year-old man was seen in an outpatient clinic affiliated with this hospital because of abdominal pain, fever, and weight loss. The patient was reportedly well until unintentional weight loss occurred approximately 6 weeks before presentation. Three weeks before presentation, upper abdominal pain developed that the patient rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. The pain radiated to his throat, increased after eating and drinking, and did not diminish with ibuprofen. At the outpatient clinic, the patient reported nausea, occasional vomiting, decreased food ... C1 [Heller, Howard M.] MIT, Dept Med, Cambridge, MA 02139 USA. [Heller, Howard M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Wu, Carol C.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Pierce, Virginia M.; Kradin, Richard L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Heller, Howard M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Wu, Carol C.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Pierce, Virginia M.; Kradin, Richard L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Heller, HM (reprint author), MIT, Dept Med, 77 Massachusetts Ave, Cambridge, MA 02139 USA. NR 14 TC 2 Z9 2 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 10 PY 2013 VL 369 IS 15 BP 1453 EP 1461 DI 10.1056/NEJMcpc1304165 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 231QE UT WOS:000325431500014 PM 24106939 ER PT J AU Haghani, M Shabani, M Moazzami, K AF Haghani, M. Shabani, M. Moazzami, K. TI MATERNAL MOBILE PHONE EXPOSURE ADVERSELY AFFECTS THE ELECTROPHYSIOLOGICAL PROPERTIES OF PURKINJE NEURONS IN RAT OFFSPRING SO NEUROSCIENCE LA English DT Article DE mobile phone exposure; pregnancy; neural excitability; Purkinje cells; offspring ID FREQUENCY ELECTROMAGNETIC-FIELDS; WI-FI SIGNAL; CELLULAR PHONES; PYRAMIDAL NEURONS; 900 MHZ; RECEPTOR ACTIVATION; MEMORY TASK; HUMAN SLEEP; IN-UTERO; RADIATION AB Electromagnetic field (EMF) radiations emitted from mobile phones may cause structural damage to neurons. With the increased usage of mobile phones worldwide, concerns about their possible effects on the nervous system are rising. In the present study, we aimed to elucidate the possible effects of prenatal EMF exposure on the cerebellum of offspring Wistar rats. Rats in the EMF group were exposed to 900-MHz pulse-EMF irradiation for 6 h per day during all gestation period. Ten offspring per each group were evaluated for behavioral and electrophysiological evaluations. Cerebellum-related behavioral dysfunctions were analyzed using motor learning and cerebellum-dependent functional tasks (Accelerated Rotarod, Hanging and Open field tests). Whole-cell patch clamp recordings were used for electrophysiological evaluations. The results of the present study failed to show any behavioral abnormalities in rats exposed to chronic EMF radiation. However, whole-cell patch clamp recordings revealed decreased neuronal excitability of Purkinje cells in rats exposed to EMF. The most prominent changes included afterhyperpolarization amplitude, spike frequency, half width and first spike latency. In conclusion, the results of the present study show that prenatal EMF exposure results in altered electrophysiological properties of Purkinje neurons. However, these changes may not be severe enough to alter the cerebellum-dependent functional tasks. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Haghani, M.] Shiraz Univ Med Sci, Dept Physiol, Shiraz, Iran. [Shabani, M.] Kerman Univ Med Sci, Kerman Neurosci Res Ctr, Kerman 7619813159, Iran. [Moazzami, K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02129 USA. RP Shabani, M (reprint author), Kerman Univ Med Sci, Kerman Neurosci Res Ctr, Dept Neurosci, Kerman 7619813159, Iran. EM haghani55@yahoo.com; shabani@kmu.ac.ir; kasra.moazzami@gmail.com NR 39 TC 14 Z9 15 U1 1 U2 31 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD OCT 10 PY 2013 VL 250 BP 588 EP 598 DI 10.1016/j.neuroscience.2013.07.049 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 223YC UT WOS:000324847400053 PM 23906636 ER PT J AU Holsen, LM Lancaster, K Klibanski, A Whitfield-Gabrieli, S Cherkerzian, S Buka, S Goldstein, JM AF Holsen, L. M. Lancaster, K. Klibanski, A. Whitfield-Gabrieli, S. Cherkerzian, S. Buka, S. Goldstein, J. M. TI HPA-AXIS HORMONE MODULATION OF STRESS RESPONSE CIRCUITRY ACTIVITY IN WOMEN WITH REMITTED MAJOR DEPRESSION SO NEUROSCIENCE LA English DT Article DE depression; stress; HPA-axis; sex differences; fMRI ID PITUITARY-ADRENAL AXIS; URINARY FREE CORTISOL; PSYCHOLOGICAL STRESS; PSYCHOSOCIAL STRESS; GLUCOSE-METABOLISM; NEURAL RESPONSE; MOOD DISORDERS; NERVOUS-SYSTEM; ACTIVATION; AMYGDALA AB Decades of clinical and basic research indicate significant links between altered hypothalamic pituitary adrenal (HPA)-axis hormone dynamics and major depressive disorder (MDD). Recent neuroimaging studies of MDD highlight abnormalities in stress response circuitry regions which play a role in the regulation of the HPA-axes. However, there is a dearth of research examining these systems in parallel, especially as related to potential trait characteristics. The current study addresses this gap by investigating neural responses to a mild visual stress challenge with real-time assessment of adrenal hormones in women with MDD in remission and controls. Fifteen women with recurrent MDD in remission (rMDD) and 15 healthy control women were scanned on a 3T Siemens MR scanner while viewing neutral and negative (stress-evoking) stimuli. Blood samples were obtained before, during, and after scanning for the measurement of HPA-axis hormone levels. Compared to controls, rMDD women demonstrated higher anxiety ratings, increased cortisol levels, and hyperactivation in the amygdala and hippocampus, p < 0.05, family-wise error (FWE)-corrected in response to the stress challenge. Among rMDD women, amygdala activation was negatively related to cortisol changes and positively associated with the duration of remission. Findings presented here provide evidence for differential effects of altered HPA-axis hormone dynamics on hyperactivity in stress response circuitry regions elicited by a well-validated stress paradigm in women with recurrent MDD in remission. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Holsen, L. M.; Lancaster, K.; Cherkerzian, S.; Goldstein, J. M.] Brigham & Womens Hosp, Dept Med, Div Womens Hlth, Boston, MA 02120 USA. [Holsen, L. M.; Goldstein, J. M.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02120 USA. [Holsen, L. M.; Klibanski, A.; Goldstein, J. M.] Harvard Univ, Sch Med, Boston, MA USA. [Klibanski, A.] Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA. [Whitfield-Gabrieli, S.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Whitfield-Gabrieli, S.; Goldstein, J. M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Charlestown, MA USA. [Whitfield-Gabrieli, S.; Goldstein, J. M.] MIT, Charlestown, MA USA. [Buka, S.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. RP Goldstein, JM (reprint author), Brigham & Womens Hosp, OBC, 3rd Floor,1620 Tremont St, Boston, MA 02120 USA. EM jill_goldstein@hms.harvard.edu RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 FU National Institutes of Health Office for Research on Women's Health and Mental Health (ORWH-NIMH) [P50 MH082679]; NIMH [K01 MH091222]; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (NIH) [UL1 RR025758] FX This work was supported by the National Institutes of Health Office for Research on Women's Health and Mental Health (ORWH-NIMH) P50 MH082679 (Goldstein, P.I.). L.M.H. was also funded by NIMH K01 MH091222. The research was conducted with support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (NIH #UL1 RR025758). We thank Jenn Watch, M.Ed. and Anne Remington for help with project management, Harlyn Aizley, M.Ed. for clinical interviewing, and Jo-Ann Donatelli, Ph.D. for her contributions to diagnostic review with Dr. Goldstein. The authors also thank Stuart Tobet, Ph.D. and Robert Handa, Ph.D. for their collaborative work with the Goldstein Lab (on P50 MH082679) regarding the impact of hormones on stress response circuitry and mood and anxiety. NR 61 TC 21 Z9 23 U1 7 U2 26 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD OCT 10 PY 2013 VL 250 BP 733 EP 742 DI 10.1016/j.neuroscience.2013.07.042 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 223YC UT WOS:000324847400064 PM 23891965 ER PT J AU Daniels, KM Zavin, A Allsup, K Joseph, J Arena, R Lazzari, AA Schulze, PC Lecker, SH Brown, J Forman, DE AF Daniels, Karla M. Zavin, Alexandra Allsup, Kelly Joseph, Jacob Arena, Ross Lazzari, Antonio A. Schulze, P. Christian Lecker, Stewart H. Brown, Jonathan Forman, Daniel E. TI Serum adiponectin in non-cachectic heart failure patients SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Adiponectin; Heart failure; Dual-energy X-ray absorptiometry ID MORTALITY C1 [Daniels, Karla M.; Joseph, Jacob; Brown, Jonathan; Forman, Daniel E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Zavin, Alexandra; Allsup, Kelly; Joseph, Jacob; Lazzari, Antonio A.; Forman, Daniel E.] VA Boston Healthcare Syst, Boston, MA USA. [Arena, Ross] Univ New Mexico, Albuquerque, NM 87131 USA. [Lazzari, Antonio A.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Schulze, P. Christian] Columbia Univ, Med Ctr, New York, NY 10027 USA. [Lecker, Stewart H.] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Lecker, Stewart H.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Forman, DE (reprint author), Brigham & Womens Hosp, Boston, MA 02115 USA. EM deforman@partners.org RI Arena, Ross/A-3141-2008 OI Arena, Ross/0000-0002-6675-1996 FU NHLBI NIH HHS [R01 HL114813] NR 8 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD OCT 9 PY 2013 VL 168 IS 4 BP 4363 EP 4364 DI 10.1016/j.ijcard.2013.05.059 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 242EG UT WOS:000326219600224 PM 23739548 ER PT J AU Hawn, MT Graham, LA Richman, JS Itani, KMF Henderson, WG Maddox, TM AF Hawn, Mary T. Graham, Laura A. Richman, Joshua S. Itani, Kamal M. F. Henderson, William G. Maddox, Thomas M. TI Risk of Major Adverse Cardiac Events Following Noncardiac Surgery in Patients With Coronary Stents SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DRUG-ELUTING STENTS; RANDOMIZED CLINICAL-TRIALS; LATE THROMBOSIS; BARE-METAL; ANTIPLATELET THERAPY; INTERVENTION; IMPLANTATION; DISCONTINUATION; MANAGEMENT; REGISTRY AB IMPORTANCE Guidelines recommend delaying noncardiac surgery in patients after coronary stent procedures for 1 year after drug-eluting stents (DES) and for 6 weeks after bare metal stents (BMS). The evidence underlying these recommendations is limited and conflicting. OBJECTIVE To determine risk factors for adverse cardiac events in patients undergoing noncardiac surgery following coronary stent implantation. DESIGN, SETTING, AND PARTICIPANTS A national, retrospective cohort study of 41 989 Veterans Affairs (VA) and non-VA operations occurring in the 24 months after a coronary stent implantation between 2000 and 2010. Nonlinear generalized additive models examined the association between timing of surgery and stent type with major adverse cardiac events (MACE) adjusting for patient, surgery, and cardiac risk factors. A nested case-control study assessed the association between perioperative antiplatelet cessation and MACE. MAIN OUTCOMES AND MEASURES A composite 30-day MACE rate of all-cause mortality, myocardial infarction, and cardiac revascularization. RESULTS Within 24 months of 124 844 coronary stent implantations (47.6% DES, 52.4% BMS), 28 029 patients (22.5%; 95% CI, 22.2%-22.7%) underwent noncardiac operations resulting in 1980 MACE (4.7%; 95% CI, 4.5%-4.9%). Time between stent and surgery was associated with MACE (<6 weeks, 11.6%; 6 weeks to <6 months, 6.4%; 6-12 months, 4.2%; >12-24 months, 3.5%; P<.001). MACE rate by stent type was 5.1% for BMS and 4.3% for DES (P<.001). After adjustment, the 3 factors most strongly associated with MACE were nonelective surgical admission (adjusted odds ratio [AOR], 4.77; 95% CI, 4.07-5.59), history of myocardial infarction in the 6 months preceding surgery (AOR, 2.63; 95% CI, 2.32-2.98), and revised cardiac risk index greater than 2 (AOR, 2.13; 95% CI, 1.85-2.44). Of the 12 variables in the model, timing of surgery ranked fifth in explanatory importance measured by partial effects analysis. Stent type ranked last, and DES was not significantly associated with MACE (AOR, 0.91; 95% CI, 0.83-1.01). After both BMS and DES placement, the risk of MACE was stable at 6 months. A case-control analysis of 284 matched pairs found no association between antiplatelet cessation and MACE (OR, 0.86; 95% CI, 0.57-1.29). CONCLUSIONS AND RELEVANCE Among patients undergoing noncardiac surgery within 2 years of coronary stent placement, MACE were associated with emergency surgery and advanced cardiac disease but not stent type or timing of surgery beyond 6 months after stent implantation. Guideline emphasis on stent type and surgical timing for both DES and BMS should be reevaluated. C1 [Hawn, Mary T.; Graham, Laura A.; Richman, Joshua S.] Birmingham Vet Adm Hosp, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Hawn, Mary T.; Richman, Joshua S.] Univ Alabama Birmingham, Dept Surg, Sect Gastrointestinal Surg, Birmingham, AL 35294 USA. [Itani, Kamal M. F.] Boston Univ, Dept Surg, VA Boston Hlth Care Syst, Boston, MA 02215 USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. [Henderson, William G.] Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. [Henderson, William G.] Colorado Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO USA. [Maddox, Thomas M.] VA Eastern Colorado Hlth Care Syst, Denver, CO USA. [Maddox, Thomas M.] Univ Colorado, Denver, CO 80202 USA. RP Hawn, MT (reprint author), Univ Alabama Birmingham, Dept Surg, Sect Gastrointestinal Surg, 1922 7th Ave S,KB 428, Birmingham, AL 35294 USA. EM mhawn@uab.edu FU VA Health Services Research & Development grant [IIR 09-347]; VA Career Development Awards FX This study is supported by a VA Health Services Research & Development grant (No. IIR 09-347). In addition, Drs Maddox and Richman are supported by VA Career Development Awards. NR 28 TC 92 Z9 93 U1 3 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 9 PY 2013 VL 310 IS 14 BP 1462 EP 1472 DI 10.1001/jama.2013.278787 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 230PK UT WOS:000325354100022 PM 24101118 ER PT J AU Bekelman, JE Epstein, AJ Emanuel, EJ AF Bekelman, Justin E. Epstein, Andrew J. Emanuel, Ezekiel J. TI Single- vs Multiple-Fraction Radiotherapy for Bone Metastases From Prostate Cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Bekelman, Justin E.] Univ Penn, Perelman Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Epstein, Andrew J.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Emanuel, Ezekiel J.] Univ Penn, Perelman Sch Med, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. RP Bekelman, JE (reprint author), Univ Penn, Perelman Sch Med, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM bekelman@uphs.upenn.edu FU NCI NIH HHS [K07 CA163616, K07-CA163616] NR 6 TC 24 Z9 24 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 9 PY 2013 VL 310 IS 14 BP 1501 EP 1502 DI 10.1001/jama.2013.277081 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 230PK UT WOS:000325354100027 PM 24104375 ER PT J AU Froberg, JE Yang, L Lee, JT AF Froberg, John E. Yang, Lin Lee, Jeannie T. TI Guided by RNAs: X-Inactivation as a Model for lncRNA Function SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE long non-coding RNA; X-inactivation; polycomb complexes ID LONG NONCODING RNAS; ES CELL-DIFFERENTIATION; BREAST-CANCER CELLS; POLYCOMB GROUP GENE; XIST RNA; ANTISENSE TRANSCRIPTION; CHROMOSOME INACTIVATION; CHROMATIN-STRUCTURE; TSIX TRANSCRIPTION; ANGELMAN SYNDROME AB The recent revolution in sequencing technology has helped to reveal a large transcriptome of long non-coding RNAs (lncRNAs). A major challenge in the years to come is to determine what biological functions, if any, they serve. Although the purpose of these transcripts is largely unknown at present, existing examples suggest that lncRNAs play roles in a wide variety of biological processes. Exemplary cases are lncRNAs within the X-inactivation center. Indeed, lncRNAs dominate control of random X-chromosome inactivation (XCI). The RNA-based regulatory mechanisms of XCI include recruitment of chromatin modifiers, formation of RNA-based subnuclear compartments, and regulation of transcription by antisense transcription. XCI and lncRNAs now also appear to be very relevant in the development and progression of cancer. This perspective focuses on new insights into lncRNA-dependent regulation of XCI, which we believe serve as paradigms for understanding lncRNA function more generally. (c) 2013 Elsevier Ltd. All rights reserved. C1 [Lee, Jeannie T.] Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Howard Hughes Med Inst, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu FU NIGMS NIH HHS [R01 GM090278, R37 GM058839] NR 100 TC 44 Z9 47 U1 3 U2 55 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD OCT 9 PY 2013 VL 425 IS 19 BP 3698 EP 3706 DI 10.1016/j.jmb.2013.06.031 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226MP UT WOS:000325040800010 PM 23816838 ER PT J AU Atassi, N Yerramilli-Rao, P Szymonifka, J Yu, H Kearney, M Grasso, D Deng, J Levine-Weinberg, M Shapiro, J Lee, A Joseph, L Macklin, EA Cudkowicz, ME AF Atassi, Nazem Yerramilli-Rao, Padmaja Szymonifka, Jackie Yu, Hong Kearney, Marianne Grasso, Daniela Deng, Jing Levine-Weinberg, Mark Shapiro, Jordan Lee, Alexandra Joseph, Lucia Macklin, Eric A. Cudkowicz, Merit E. TI Analysis of start-up, retention, and adherence in ALS clinical trials SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; COOPERATIVE-ONCOLOGY-GROUP; PREVENTION TRIALS; RECRUITMENT; DISEASE; COSTS; CHALLENGES; DEMENTIA; MG/DAY; IMPACT AB Objective: To investigate predictors of trial start-up times, high attrition, and poor protocol adherence in amyotrophic lateral sclerosis (ALS) trials. Methods: Retrospective analysis of start-up times, retention, and protocol adherence was performed on 5 clinical studies conducted by the Northeast ALS Consortium and 50 ALS clinical trials identified by PubMed search. Predictors of start-up times were estimated by accelerated failure time models with random effects. Predictors of retention and protocol deviations were estimated by mixed-model logistic regression. Results: Median times for contract execution and institutional review board (IRB) approval were 105 days and 125 days, respectively. Contract execution was faster at sites with more ongoing trials (p = 0.005), and more full-time (p = 0.006) and experienced (p < 0.001) coordinators. IRB approval was faster at sites with more ongoing trials (p = 0.010) and larger ALS clinics (p = 0.038). Site activation after IRB approval was faster at sites with more full-time (p = 0.038) and experienced (p < 0.001) coordinators. Twenty-two percent of surviving participants withdrew before completing the trial. Better participant functional score at baseline was an independent predictor of trial completion (odds ratio 1.29, p = 0.002) and fewer protocol deviations (odds ratio 0.86, p = 0.030). Conclusion: Delays in IRB review contribute the most to prolonged trial start-up times, and these timelines are faster in sites with more experienced staff. Strategies to improve protocol adherence and participants' retention may include enrolling people at early disease stages. C1 [Atassi, Nazem; Yerramilli-Rao, Padmaja; Yu, Hong; Kearney, Marianne; Grasso, Daniela; Deng, Jing; Levine-Weinberg, Mark; Shapiro, Jordan; Lee, Alexandra; Joseph, Lucia; Cudkowicz, Merit E.] Massachusetts Gen Hosp, Neurol Clin Res Inst, Dept Neurol, Boston, MA 02114 USA. [Szymonifka, Jackie; Macklin, Eric A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Atassi, Nazem; Yerramilli-Rao, Padmaja; Macklin, Eric A.; Cudkowicz, Merit E.] Harvard Univ, Sch Med, Boston, MA USA. RP Atassi, N (reprint author), Massachusetts Gen Hosp, Neurol Clin Res Inst, Dept Neurol, Boston, MA 02114 USA. EM na.tassi@partners.org FU Muscular Dystrophy Association (MDA); American Academy of Neurology (AAN); MGH ALS Research Fund; National Institute of Neurological Disorders and Stroke [U01-NS049640, U01-NS049640-04S1] FX Supported by institutional funding. This work was conducted with support from the Muscular Dystrophy Association (MDA) Clinical Research Training Grant, research fellowship from the American Academy of Neurology (AAN), the MGH ALS Research Fund, and the National Institute of Neurological Disorders and Stroke U01-NS049640 and U01-NS049640-04S1. NR 27 TC 3 Z9 3 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD OCT 8 PY 2013 VL 81 IS 15 BP 1350 EP 1355 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA AA0EQ UT WOS:000330768600015 PM 24005339 ER PT J AU Skalnikova, HK Navarro, R Marsala, S Hrabakova, R Vodicka, P Gadher, SJ Kovarova, H Marsala, M AF Skalnikova, Helena Kupcova Navarro, Roman Marsala, Silvia Hrabakova, Rita Vodicka, Petr Gadher, Suresh Jivan Kovarova, Hana Marsala, Martin TI Signaling proteins in spinal parenchyma and dorsal root ganglion in rat with spinal injury-induced spasticity SO JOURNAL OF PROTEOMICS LA English DT Article DE Spinal cord trauma; Spasticity; Hyper-reflexia; Proteomic profiling; Dorsal root ganglia; Spinal gray matter ID COLONY-STIMULATING FACTOR; CORD-INJURY; NEUROPATHIC PAIN; MECHANICAL ALLODYNIA; MULTIPLE-SCLEROSIS; PROTEOMIC ANALYSIS; DOWN-REGULATION; NERVOUS-SYSTEM; KINASE; EXPRESSION AB Development of progressive muscle spasticity resulting from spinal traumatic injury can be mediated by loss of local segmental inhibition and/or by an increased sensory afferent drive with resulting exacerbated a-motoneuron activity. To identify potential contributions of neuroactive substances in the development of such spasticity state, we employed a well-defined spinal injury-evoked spasticity rat model. Signaling molecules were analyzed in the spinal parenchyma below the level of spinal injury and in the corresponding dorsal root ganglion cells using Kinex (TM) antibody microarrays. The results uncovered the involvement of angiogenesis and neurodegeneration pathways together with direct cross-talk mediated by several hub proteins with SH-2 domains. At 2 and 5 weeks after transection, up-regulation of several proteins including CaMKIV, RON alpha and PKC delta as well as MAPK3/ERK1 phosphorylation was observed in the spinal ventral horns. Our results indicate that these signaling molecules and their neuronal effector systems cannot only play an important role in the initiation but also in the maintenance of spasticity states after spinal trauma. The exclusivity of specific protein changes observed in lumbar spinal parenchyma but not in dorsal root ganglia indicates that new treatment strategies should primarily target specific spinal segments to prevent or attenuate spasticity states. Biological significance Development of progressive muscle spasticity and rigidity represents a serious complication associated with spinal ischemic or traumatic injury. Signaling proteins, including their phosphorylation status, were analyzed in the spinal parenchyma below the level of spinal injury and in the corresponding dorsal root ganglion cells in a rat model of spinal injury using Kinex (TM) antibody microarrays. The results uncovered direct protein interaction mediated cross-talk between angiogenesis and neurodegeneration pathways, which may significantly contribute to the healing process in the damaged region. Importantly, we identified several target proteins exclusively observed in the spinal lumbar ventral horns, where such proteins may not only play an important role in the initiation but also in the maintenance of spasticity states after spinal trauma. Hence, potential new treatment strategies such as gene silencing or drug treatment should primarily target spinal parenchymal sites at and around the injury epicenter and most likely employ intrathecal or targeted spinal segment-specific vector or drug delivery. We believe that this work will stimulate future translational research, ultimately leading to the improvement of quality of life of patients with spinal traumatic injury. (C) 2013 Elsevier B.V. All rights reserved. C1 [Skalnikova, Helena Kupcova; Hrabakova, Rita; Kovarova, Hana] Acad Sci Czech Republic, Inst Anim Physiol & Genet, Lab Biochem & Mol Biol Germ Cells, Vvi, Libechov, Czech Republic. [Navarro, Roman; Marsala, Silvia; Marsala, Martin] Univ Calif San Diego, Dept Anesthesiol, San Diego, CA 92103 USA. [Vodicka, Petr] Acad Sci Czech Republic, Inst Anim Physiol & Genet, Lab Cell Regenerat & Plast, Vvi, Libechov, Czech Republic. [Vodicka, Petr] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Gadher, Suresh Jivan] Life Technol, Frederick, MD USA. [Marsala, Martin] Slovak Acad Sci, Inst Neurobiol, Kosice 04001, Slovakia. RP Kovarova, H (reprint author), Acad Sci Czech Republic, Inst Anim Physiol & Genet, Lab Biochem & Mol Biol Germ Cells, Vvi, Libechov, Czech Republic. EM kovarova@iapg.cas.cz RI Hrabakova, Rita/G-7136-2014; Kupcova Skalnikova, Helena/G-7138-2014; Kovarova, Hana/G-7135-2014; Vodicka, Petr/C-3845-2009 OI Vodicka, Petr/0000-0002-6605-9158 FU MEYS [ME10044]; NIH [NS051644]; TACR [TA01011466]; Institutional Research Concept [RV067985904]; Operational Program Research and Development for Innovations [CZ.1.05/2.1.00/03.0124] FX This work was supported in part by MEYS (ME10044; H.K.), NIH (NS051644; M.M.), TACR (TA01011466; HK), and Institutional Research Concept RV067985904 (IAPG, AS CR, v.v.i). Infrastructural part of this project was supported from the Operational Program Research and Development for Innovations (CZ.1.05/2.1.00/03.0124). NR 73 TC 7 Z9 7 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-3919 EI 1876-7737 J9 J PROTEOMICS JI J. Proteomics PD OCT 8 PY 2013 VL 91 BP 41 EP 57 DI 10.1016/j.jprot.2013.06.028 PG 17 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 264UH UT WOS:000327906000004 ER PT J AU Leyton, PA Beppu, H Pappas, A Martyn, TM Derwall, M Baron, DM Galdos, R Bloch, DB Bloch, KD AF Leyton, Patricio A. Beppu, Hideyuki Pappas, Alexandra Martyn, Trejeeve M. Derwall, Matthias Baron, David M. Galdos, Rita Bloch, Donald B. Bloch, Kenneth D. TI Deletion of the Sequence Encoding the Tail Domain of the Bone Morphogenetic Protein type 2 Receptor Reveals a Bone Morphogenetic Protein 7-Specific Gain of Function SO PLOS ONE LA English DT Article ID PRIMARY PULMONARY-HYPERTENSION; II RECEPTOR; ARTERIAL-HYPERTENSION; INCREASED SUSCEPTIBILITY; SIGNAL-TRANSDUCTION; MICE; BMPR2; MUTATIONS; GENERATION; CLONING AB The bone morphogenetic protein (BMP) type II receptor (BMPR2) has a long cytoplasmic tail domain whose function is incompletely elucidated. Mutations in the tail domain of BMPR2 are found in familial cases of pulmonary arterial hypertension. To investigate the role of the tail domain of BMPR2 in BMP signaling, we generated a mouse carrying a Bmpr2 allele encoding a non-sense mediated decay-resistant mutant receptor lacking the tail domain of Bmpr2. We found that homozygous mutant mice died during gastrulation, whereas heterozygous mice grew normally without developing pulmonary arterial hypertension. Using pulmonary artery smooth muscle cells (PaSMC) from heterozygous mice, we determined that the mutant receptor was expressed and retained its ability to transduce BMP signaling. Heterozygous PaSMCs exhibited a BMP7-specific gain of function, which was transduced via the mutant receptor. Using siRNA knockdown and cells from conditional knockout mice to selectively deplete BMP receptors, we observed that the tail domain of Bmpr2 inhibits Alk2-mediated BMP7 signaling. These findings suggest that the tail domain of Bmpr2 is essential for normal embryogenesis and inhibits Alk2-mediated BMP7 signaling in PaSMCs. C1 [Leyton, Patricio A.; Beppu, Hideyuki; Pappas, Alexandra; Martyn, Trejeeve M.; Derwall, Matthias; Baron, David M.; Bloch, Donald B.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. [Leyton, Patricio A.; Beppu, Hideyuki; Pappas, Alexandra; Martyn, Trejeeve M.; Derwall, Matthias; Baron, David M.; Galdos, Rita; Bloch, Donald B.; Bloch, Kenneth D.] Harvard Univ, Sch Med, Boston, MA USA. [Beppu, Hideyuki] Toyama Univ, Grad Sch Med & Pharmaceut Sci, Dept Clin Lab & Mol Pathol, Toyama 930, Japan. [Derwall, Matthias] Rhein Westfal TH Aachen, Uniklin Aachen, Dept Anesthesiol, Aachen, North Rhine Wes, Germany. [Baron, David M.] Med Univ Vienna, Dept Anesthesia Gen Intens Care & Pain Management, Vienna, Austria. [Galdos, Rita; Bloch, Donald B.] Massachusetts Gen Hosp, Dept Med, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Bloch, Kenneth D.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Leyton, PA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. EM pleyton@partners.org FU National Institutes of Health Heart, Lung and Blood Institute [HL074352]; Deutsche Forschungsgemeinschaft [DE-1685-1/1] FX Funding came from National Institutes of Health Heart, Lung and Blood Institute HL074352, http://www.nhlbi.nih.gov, DE-1685-1/1, Deutsche Forschungsgemeinschaft, http://www.dfg.de/en/. The funders had no role in study design, data collection and analysis, decisio to publish, or preparation of the manuscript. NR 33 TC 8 Z9 8 U1 2 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 OCT 8 PY 2013 VL 8 IS 10 AR e76947 DI 10.1371/journal.pone.0076947 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 233FK UT WOS:000325552200087 PM 24116187 ER PT J AU Martin, ME Bhatnagar, S George, MD Paster, BJ Canfield, DR Eisen, JA Solnick, JV AF Martin, Miriam E. Bhatnagar, Srijak George, Michael D. Paster, Bruce J. Canfield, Don R. Eisen, Jonathan A. Solnick, Jay V. TI The Impact of Helicobacter pylori Infection on the Gastric Microbiota of the Rhesus Macaque SO PLOS ONE LA English DT Article ID 16S RIBOSOMAL-RNA; BACTERIAL MICROBIOTA; MAXIMUM-LIKELIHOOD; SPIRAL BACTERIA; GUT MICROBIOTA; MONKEYS; HEILMANNII; DIVERSITY; HEALTH; IDENTIFICATION AB Helicobacter pylori colonization is highly prevalent among humans and causes significant gastric disease in a subset of those infected. When present, this bacterium dominates the gastric microbiota of humans and induces antimicrobial responses in the host. Since the microbial context of H. pylori colonization influences the disease outcome in a mouse model, we sought to assess the impact of H. pylori challenge upon the pre-existing gastric microbial community members in the rhesus macaque model. Deep sequencing of the bacterial 16S rRNA gene identified a community profile of 221 phylotypes that was distinct from that of the rhesus macaque distal gut and mouth, although there were taxa in common. High proportions of both H. pylori and H. suis were observed in the post-challenge libraries, but at a given time, only one Helicobacter species was dominant. However, the relative abundance of non-Helicobacter taxa was not significantly different before and after challenge with H. pylori. These results suggest that while different gastric species may show competitive exclusion in the gastric niche, the rhesus gastric microbial community is largely stable despite immune and physiological changes due to H. pylori infection. C1 [Martin, Miriam E.; Solnick, Jay V.] Univ Calif Davis, Dept Med, Davis, CA 95616 USA. [Martin, Miriam E.; Bhatnagar, Srijak; George, Michael D.; Eisen, Jonathan A.; Solnick, Jay V.] Univ Calif Davis, Dept Microbiol & Immunol, Davis, CA 95616 USA. [Bhatnagar, Srijak; Eisen, Jonathan A.] Univ Calif Davis, Dept Ecol & Evolut, Davis, CA 95616 USA. [Bhatnagar, Srijak] Univ Calif Davis, Microbiol Grad Grp, Davis, CA 95616 USA. [Canfield, Don R.; Solnick, Jay V.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. [Paster, Bruce J.] Forsyth Inst, Cambridge, MA USA. RP Solnick, JV (reprint author), Univ Calif Davis, Dept Med, Davis, CA 95616 USA. EM jvsolnick@ucdavis.edu OI Bhatnagar, Srijak/0000-0003-0240-2655; Eisen, Jonathan A./0000-0002-0159-2197; Solnick, Jay/0000-0002-7435-8393 FU National Institutes of Health [R21 AI080788, R21 DE020025] FX Funding was provided by grants from the National Institutes of Health to JVS (R21 AI080788) and to MDG (R21 DE020025). http://www.nih.gov/. The sponsors of this research had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 12 Z9 13 U1 1 U2 18 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 8 PY 2013 VL 8 IS 10 AR e76375 DI 10.1371/journal.pone.0076375 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 233FK UT WOS:000325552200052 PM 24116104 ER PT J AU Shioda, T Rosenthal, NF Coser, KR Suto, M Phatak, M Medvedovic, M Carey, VJ Isselbacher, KJ AF Shioda, Toshi Rosenthal, Noel F. Coser, Kathryn R. Suto, Mizuki Phatak, Mukta Medvedovic, Mario Carey, Vincent J. Isselbacher, Kurt J. TI Expressomal approach for comprehensive analysis and visualization of ligand sensitivities of xenoestrogen responsive genes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ENDOCRINE-DISRUPTING CHEMICALS; BREAST-CANCER CELLS; ESTROGEN-RECEPTOR-ALPHA; PUBLIC-HEALTH; EXPOSURE; PHYTOESTROGENS; PRINCIPLES; STATEMENT; SOCIETY; DISEASE AB Although biological effects of endocrine disrupting chemicals (EDCs) are often observed at unexpectedly low doses with occasional nonmonotonic dose-response characteristics, transcriptome-wide profiles of sensitivities or dose-dependent behaviors of the EDC responsive genes have remained unexplored. Here, we describe expressome analysis for the comprehensive examination of dose-dependent gene responses and its applications to characterize estrogen responsive genes in MCF-7 cells. Transcriptomes of MCF-7 cells exposed to varying concentrations of representative natural and xenobiotic estrogens for 48 h were determined by microarray and used for computational calculation of interpolated approximations of estimated transcriptomes for 300 doses uniformly distributed in log space for each chemical. The entire collection of these estimated transcriptomes, designated as the expressome, has provided unique opportunities to profile chemical-specific distributions of ligand sensitivities for large numbers of estrogen responsive genes, revealing that at low concentrations estrogens generally tended to suppress rather than to activate transcription. Gene ontology analysis demonstrated distinct functional enrichment between high-and low-sensitivity estrogen responsive genes, supporting the notion that a single EDC chemical can cause qualitatively distinct biological responses at different doses. Expressomal heatmap visualization of dose-dependent induction of Bisphenol A inducible genes showed a weak gene activation peak at a very low concentration range (ca. 0.1 nM) in addition to the main, strong gene activation peak at and above 100 nM. Thus, expressome analysis is a powerful approach to understanding the EDC dose-dependent dynamic changes in gene expression at the transcriptomal level, providing important information on the overall profiles of ligand sensitivities and nonmonotonic responses. C1 [Shioda, Toshi; Rosenthal, Noel F.; Coser, Kathryn R.; Suto, Mizuki; Isselbacher, Kurt J.] Massachusetts Gen Hosp, Mol Profiling Lab, Ctr Canc Res, Charlestown, MA 02129 USA. [Shioda, Toshi; Carey, Vincent J.; Isselbacher, Kurt J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Phatak, Mukta; Medvedovic, Mario] Univ Cincinnati, Coll Med, Lab Stat Genom & Syst Biol, Dept Environm Hlth, Cincinnati, OH 45267 USA. [Carey, Vincent J.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. RP Shioda, T (reprint author), Massachusetts Gen Hosp, Mol Profiling Lab, Ctr Canc Res, Charlestown, MA 02129 USA. EM tshioda@partners.org; kisselbacher@partners.org FU Susan G. Komen for Cure Grants [FAS0703860, KG090515]; NIH [U41-HG004059, R01-HL086601] FX This study was supported by Susan G. Komen for Cure Grants FAS0703860 and KG090515 (to T.S.) and NIH Grants U41-HG004059 and R01-HL086601 (to V.J.C.). NR 29 TC 8 Z9 8 U1 0 U2 14 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 OCT 8 PY 2013 VL 110 IS 41 BP 16508 EP 16513 DI 10.1073/pnas.1315929110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 231ED UT WOS:000325395600056 PM 24062438 ER PT J AU Raitt, MH AF Raitt, Merritt H. TI Inappropriate Implantable Defibrillator Shocks SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE beta-blockers; carvedilol; defibrillator; heart failure; inappropriate therapy ID CARDIAC-RESYNCHRONIZATION THERAPY; HEART-FAILURE; CARDIOVERTER-DEFIBRILLATORS; BETA-BLOCKERS; CARVEDILOL; METOPROLOL; METAANALYSIS; PREVENTION; OUTCOMES; TRIAL C1 [Raitt, Merritt H.] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Div Cardiol, Portland, OR 97201 USA. [Raitt, Merritt H.] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97201 USA. RP Raitt, MH (reprint author), Portland VA Med Ctr, P-3 CARD,3710 SW US Vet Rd, Portland, OR 97239 USA. EM merritt.raitt@va.gov NR 14 TC 2 Z9 2 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 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 8 PY 2013 VL 62 IS 15 BP 1351 EP 1352 DI 10.1016/j.jacc.2013.05.055 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 225ZY UT WOS:000325005000008 PM 23770170 ER PT J AU Zhang, JH Palevsky, PM Chertow, GM Hartigan, J O'Connor, TZ Guarino, P Zhou, BQ AF Zhang, Jane H. Palevsky, Paul M. Chertow, Glenn M. Hartigan, John O'Connor, Theresa Z. Guarino, Peter Zhou, Bingqing TI Piecewise Analysis of Patient Survival after Onset of AKI SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE-RENAL-FAILURE; CRITICALLY-ILL PATIENTS; MORTALITY; EPIDEMIOLOGY; INTENSITY; OUTCOMES; THERAPY; SUPPORT; TRIAL; POINT AB Background and objectivesAKI affects approximately 2%-7% of hospitalized patients and >35% of critically ill patients. Survival after AKI may be described as having an acute phase (including an initial hyperacute component) followed by a convalescent phase, which may itself have early and late components.Design, setting, participants, & measurementsData from the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network (ATN) study was used to model mortality risk among patients with dialysis-requiring AKI. This study assumed that the mortality hazard can be described by a piecewise log-linear function with change points. Using an average likelihood method, the authors tested for the number of change points in a piecewise log-linear hazard model. The maximum likelihood approach to locate the change point(s) was then adopted, and associated parameters and standard errors were estimated.ResultsThere were 1124 ATN participants with follow-up to 1 year. The mortality hazard of AKI decreased over time with inflections in the rate of decrease at days 4, 42, and 148, with the sharpest change at day 42. The daily rate of decline in the log of the hazard for death was 0.220 over the first 4 days, 0.046 between day 4 and day 42, 0.017 between day 42 and day 148, and 0.003 between day 148 and day 365.ConclusionsThere appear to be two major phases of mortality risk after AKI: an early phase extending over the first 6 weeks and a late phase from 6 weeks to 1 year. Within the first 42 days, this can be further divided into hyperacute (days 1-4) and acute (days 4-42) phases. After 42 days, there appear to be early (days 42-148) and late (after day 148) convalescent phases. These findings may help to inform the design of AKI clinical trials and assist critical care physicians in prognostic stratification. C1 [Zhang, Jane H.; O'Connor, Theresa Z.; Guarino, Peter; Zhou, Bingqing] Vet Affairs Connecticut Hlth Care Syst, Cooperat Studies Program Coordinating Ctr, West Haven, CT 06516 USA. [Palevsky, Paul M.] Vet Affairs Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Chertow, Glenn M.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Hartigan, John] Yale Univ, Dept Stat, New Haven, CT USA. [Zhou, Bingqing] Yale Univ, Sch Publ Hlth, Div Biostat, New Haven, CT USA. RP Zhang, JH (reprint author), Vet Affairs Connecticut Hlth Care Syst, Cooperat Studies Program Coordinating Ctr, 950 Campbell Ave, West Haven, CT 06516 USA. EM Jane.Zhang@va.gov OI Palevsky, Paul/0000-0002-7334-5400 FU Department of Veterans Affairs Office of Research and Development; National Institute of Diabetes and Digestive and Kidney Diseases [Y1-DK-3508-01] FX This study was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development and by the National Institute of Diabetes and Digestive and Kidney Diseases (interagency agreement Y1-DK-3508-01). NR 19 TC 4 Z9 4 U1 0 U2 1 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 OCT 7 PY 2013 VL 8 IS 10 BP 1679 EP 1684 DI 10.2215/CJN.07250712 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 229MA UT WOS:000325268200008 PM 23813558 ER PT J AU Kim, J Lee, S Jeong, Y Kim, JK Jung, YM Merenda, F Salathe, RP Shin, JS Oh, K AF Kim, Jongki Lee, Sungrae Jeong, Yoonseob Kim, Jun-Ki Jung, Yongmin Merenda, Fabrice Salathe, Rene-Paul Shin, Jeon-Soo Oh, Kyunghwan TI Crossed fiber optic Bessel beams for curvilinear optofluidic transport of dielectric particles SO OPTICS EXPRESS LA English DT Article ID WAVE-GUIDES; LIGHT-BEAM; TWEEZERS; TRAP; GENERATION; MICROMANIPULATION; MANIPULATION; PROPAGATION; AIR AB Due to its unique non-diffracting and self-reconstructing nature, Bessel beams have been successfully adopted to trap multiple particles along the beam's axial direction. However, prior bulk-optic based Bessel beams have a fundamental form-factor limitation for in situ, in-vitro, and in-vivo applications. Here we present a novel implementation of Fourier optics along a single strand of hybrid optical fiber in a monolithic manner that can generate pseudo Bessel beam arrays in two-dimensional space. We successfully demonstrate unique optofluidic transport of the trapped dielectric particles along a curvilinear optical route by multiplexing the fiber optic pseudo Bessel beams. The proposed technique can form a new building block to realize reconfigurable optofluidic transportation of particulates that can break the limitations of both prior bulk-optic Bessel beam generation techniques and conventional microfluidic channels. (C) 2013 Optical Society of America C1 [Kim, Jongki; Lee, Sungrae; Jeong, Yoonseob; Oh, Kyunghwan] Yonsei Univ, Dept Phys, Coll Sci, Seoul 120749, South Korea. [Kim, Jun-Ki] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Jung, Yongmin] Univ Southampton Highfield, Optoelect Res Ctr, Southampton SO17 1BJ, Hants, England. [Merenda, Fabrice; Salathe, Rene-Paul] Ecole Polytech Fed Lausanne, Adv Photon Lab, CH-1015 Lausanne, Switzerland. [Shin, Jeon-Soo] Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Dept Microbiol, Seoul 120752, South Korea. RP Oh, K (reprint author), Yonsei Univ, Dept Phys, Coll Sci, Seoul 120749, South Korea. EM koh@yonsei.ac.kr FU Brain Korea 21Project; NRF of Korea; Korea government (MEST) [2011-00181613, 2012M3A7B4049800]; Seoul RBD Program [PA110081] FX This work was supported in part by the Brain Korea 21Project, in part by the NRF of Korea and a grant funded by the Korea government (MEST) (2011-00181613, 2012M3A7B4049800), in part by the Seoul R&BD Program (PA110081) NR 35 TC 3 Z9 3 U1 0 U2 16 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD OCT 7 PY 2013 VL 21 IS 20 BP 23021 EP 23029 DI 10.1364/OE.21.023021 PG 9 WC Optics SC Optics GA 233EU UT WOS:000325549800002 PM 24104217 ER PT J AU Sung, YJ Gupta, R AF Sung, Yongjin Gupta, Rajiv TI X-ray phase tomography of a moving object SO OPTICS EXPRESS LA English DT Article ID OPTICAL DIFFRACTION TOMOGRAPHY; DARK-FIELD; MICROTOMOGRAPHY; INTERFEROMETRY; REGULARIZATION; SCATTERING; RETRIEVAL AB We propose an algorithm for tomographic reconstruction of the refractive index map of an object translated across a fan-shaped X-ray beam. We adopt a forward image model valid under the non-paraxial condition, and use a unique mapping of the acquired projection images to reduce the computational cost. Even though the imaging setup affords only a limited angular coverage, our algorithm provides accurate refractive index values by employing the positivity and piecewise-smoothness constraints. (C) 2013 Optical Society of America C1 [Sung, Yongjin] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Sung, Yongjin; Gupta, Rajiv] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Sung, Yongjin; Gupta, Rajiv] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sung, YJ (reprint author), MIT, Dept Mech Engn, Cambridge, MA 02139 USA. EM yongjin.sung@gmail.com FU Department of Homeland Security's Science and Technology Directorate [HSHQDC-11-C-0083]; National Research Foundation of Singapore through the Singapore-MIT Alliance for Research and Technology Centre; DARPA AXiS [N66001-11-4204, 1300217190] FX This work was supported by the Department of Homeland Security's Science and Technology Directorate through contract HSHQDC-11-C-0083, the National Research Foundation of Singapore through the Singapore-MIT Alliance for Research and Technology Centre, and the DARPA AXiS program (Grant No. N66001-11-4204, P.R. No. 1300217190). The authors thank Prof. George Barbastathis and Dr. Niyom Lue for useful discussion. NR 39 TC 0 Z9 0 U1 2 U2 5 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD OCT 7 PY 2013 VL 21 IS 20 BP 23671 EP 23678 DI 10.1364/OE.21.023671 PG 8 WC Optics SC Optics GA 233EU UT WOS:000325549800064 PM 24104279 ER PT J AU Landry, G Seco, J Gaudreault, M Verhaegen, F AF Landry, Guillaume Seco, Joao Gaudreault, Mathieu Verhaegen, Frank TI Deriving effective atomic numbers from DECT based on a parameterization of the ratio of high and low linear attenuation coefficients SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID ENERGY COMPUTED-TOMOGRAPHY; X-RAY CT; DENSITY; SCANNER; TISSUES; RECONSTRUCTION; SIMULATION; RADIATION; MODELS; SINGLE AB Dual energy computed tomography (DECT) can provide simultaneous estimation of relative electron density rho(e) and effective atomic number Z(eff). The ability to obtain these quantities (rho(e), Z(eff)) has been shown to benefit selected radiotherapy applications where tissue characterization is required. The conventional analysis method (spectral method) relies on knowledge of the CT scanner photon spectra which may be difficult to obtain accurately. Furthermore an approximate empirical attenuation correction of the photon spectrum through the patient is necessary. We present an alternative approach based on a parameterization of the measured ratio of low and high kVp linear attenuation coefficients for deriving Z(eff) which does not require the estimation of the CT scanner spectra. In a first approach, the tissue substitute method (TSM), the Rutherford parameterization of the linear attenuation coefficients was employed to derive a relation between Z(eff) and the ratio of the linear attenuation coefficients measured at the low and high kVp of the CT scanner. A phantom containing 16 tissue mimicking inserts was scanned with a dual source DECT scanner at 80 and 140 kVp. The data from the 16 inserts phantom was used to obtain model parameters for the relation between Z(eff) and mu vertical bar(80kVp)(140kVp). The accuracy of the method was evaluated with a second phantom containing 4 tissue mimicking inserts. The TSM was compared to a more complex approach, the reference tissue method (RTM), which requires the derivation of stoichiometric fit parameters. These were derived from the 16 inserts phantom scans and used to calculate CT numbers at 80 and 140 kVp for a set of tabulated reference human tissues. Model parameters for the parameterization of mu vertical bar(80kVp)(140 kVp) were estimated for this reference tissue dataset and compared to the results of the TSM. Residuals on Z(eff) for the reference tissue dataset for both TSM and RTM were compared to those obtained from the spectral method. The tissue substitutes were well fitted by the TSM with R-2 = 0.9930. Residuals on Z(eff) for the phantoms were similar between the TSM and spectral methods for Z(eff) < 8 while they were improved by the TSM for higher Z(eff). The RTM fitted the reference tissue dataset well with R-2 = 0.9999. Comparing the Z(eff) extracted from TSM and the more complex RTM to the known values from the reference tissue dataset yielded errors of up to 0.3 and 0.15 units of Z(eff) respectively. The parameterization approach yielded standard deviations which were up to 0.3 units of Z(eff) higher than those observed with the spectral method for Z(eff) around 7.5. Procedures for the DECT estimation of Z(eff) removing the need for estimates of the CT scanner spectra have been presented. Both the TSM and the more complex RTM performed better than the spectral method. The RTM yielded the best results for the reference human tissue dataset reducing errors from up to 0.3 to 0.15 units of Z(eff) compared to the simpler TSM. Both TSM and RTM are simpler to implement than the spectral method which requires estimates of the CT scanner spectra. C1 [Landry, Guillaume; Gaudreault, Mathieu; Verhaegen, Frank] MUMC, Dept Radiat Oncol MAASTRO, GROW Sch Oncol & Dev Biol, NL-6201 BN Maastricht, Netherlands. [Seco, Joao] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Seco, Joao] Harvard Univ, Sch Med, Boston, MA USA. [Gaudreault, Mathieu] CHU Quebec, Dept Radiooncol, Quebec City, PQ, Canada. [Gaudreault, Mathieu] CHU Quebec, Ctr Rech, Quebec City, PQ, Canada. [Gaudreault, Mathieu] Univ Laval, Dept Phys Genie Phys & Opt, Quebec City, PQ, Canada. [Gaudreault, Mathieu] Univ Laval, Ctr Rech Cancerol, Quebec City, PQ, Canada. [Verhaegen, Frank] McGill Univ, Dept Oncol, Med Phys Unit, Montreal, PQ, Canada. RP Landry, G (reprint author), MUMC, Dept Radiat Oncol MAASTRO, GROW Sch Oncol & Dev Biol, NL-6201 BN Maastricht, Netherlands. EM frank.verhaegen@maastro.nl FU O'Brien Foundation FX Dr Joachim E Wildberger is acknowledged for providing access to the DECT scanner. We thank Dr Bernhard Schmidt from Siemens Medical for providing information on the operation of the DECT scanner. Frank P Eschbach and Jasper P Jansen are acknowledged for adapting scripts to analyze the Gammex 467 phantom measurements. We acknowledge Gammex RMI and Vladimir Varchena of CIRS for divulging phantom compositions. GL would like to acknowledge the O'Brien Foundation for funding. Patrick V Granton is acknowledged for commenting on the paper. NR 23 TC 17 Z9 19 U1 1 U2 13 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD OCT 7 PY 2013 VL 58 IS 19 BP 6851 EP 6866 DI 10.1088/0031-9155/58/19/6851 PG 16 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 220HN UT WOS:000324573600015 PM 24025623 ER PT J AU van de Water, S Kraan, AC Breedveld, S Schillemans, W Teguh, DN Kooy, HM Madden, TM Heijmen, BJM Hoogeman, MS AF van de Water, S. Kraan, A. C. Breedveld, S. Schillemans, W. Teguh, D. N. Kooy, H. M. Madden, T. M. Heijmen, B. J. M. Hoogeman, M. S. TI Improved efficiency of multi-criteria IMPT treatment planning using iterative resampling of randomly placed pencil beams SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID MODULATED PROTON THERAPY; ROBOTIC RADIOSURGERY; OPTIMIZATION; UNCERTAINTIES; RADIOTHERAPY; CANCER; PLANS AB This study investigates whether 'pencil beam resampling', i.e. iterative selection and weight optimization of randomly placed pencil beams (PBs), reduces optimization time and improves plan quality for multi-criteria optimization in intensity-modulated proton therapy, compared with traditional modes in which PBs are distributed over a regular grid. Resampling consisted of repeatedly performing: (1) random selection of candidate PBs from a very fine grid, (2) inverse multi-criteria optimization, and (3) exclusion of low-weight PBs. The newly selected candidate PBs were added to the PBs in the existing solution, causing the solution to improve with each iteration. Resampling and traditional regular grid planning were implemented into our in-house developed multi-criteria treatment planning system 'Erasmus iCycle'. The system optimizes objectives successively according to their priorities as defined in the so-called 'wish-list'. For five head-and-neck cancer patients and two PB widths (3 and 6 mm sigma at 230 MeV), treatment plans were generated using: (1) resampling, (2) anisotropic regular grids and (3) isotropic regular grids, while using varying sample sizes (resampling) or grid spacings (regular grid). We assessed differences in optimization time (for comparable plan quality) and in plan quality parameters (for comparable optimization time). Resampling reduced optimization time by a factor of 2.8 and 5.6 on average (7.8 and 17.0 at maximum) compared with the use of anisotropic and isotropic grids, respectively. Doses to organs-at-risk were generally reduced when using resampling, with median dose reductions ranging from 0.0 to 3.0Gy (maximum: 14.3Gy, relative: 0%-42%) compared with anisotropic grids and from -0.3 to 2.6 Gy (maximum: 11.4 Gy, relative: -4%-19%) compared with isotropic grids. Resampling was especially effective when using thin PBs (3 mm sigma). Resampling plans contained on average fewer PBs, energy layers and protons than anisotropic grid plans and more energy layers and protons than isotropic grid plans. In conclusion, resampling resulted in improved plan quality and in considerable optimization time reduction compared with traditional regular grid planning. C1 [van de Water, S.; Kraan, A. C.; Breedveld, S.; Schillemans, W.; Teguh, D. N.; Heijmen, B. J. M.; Hoogeman, M. S.] Erasmus MC Daniel den Hoed Canc Ctr, Dept Radiat Oncol, NL-3075 EA Rotterdam, Netherlands. [Kooy, H. M.; Madden, T. M.] Massachusetts Gen Hosp, Dept Radiat Oncol, FH Burr Proton Therapy Ctr, Boston, MA 02114 USA. [Kooy, H. M.; Madden, T. M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP van de Water, S (reprint author), Erasmus MC Daniel den Hoed Canc Ctr, Dept Radiat Oncol, Groene Hilledijk 301, NL-3075 EA Rotterdam, Netherlands. EM s.vandewater@erasmusmc.nl NR 18 TC 7 Z9 7 U1 0 U2 5 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD OCT 7 PY 2013 VL 58 IS 19 BP 6969 EP 6983 DI 10.1088/0031-9155/58/19/6969 PG 15 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 220HN UT WOS:000324573600022 PM 24029721 ER PT J AU Cervantes, TM Bassett, EK Tseng, A Kimura, A Roscioli, N Randolph, MA Vacanti, JP Hadlock, TA Gupta, R Pomerantseva, I Sundback, CA AF Cervantes, Thomas M. Bassett, Erik K. Tseng, Alan Kimura, Anya Roscioli, Nick Randolph, Mark A. Vacanti, Joseph P. Hadlock, Theresa A. Gupta, Rajiv Pomerantseva, Irina Sundback, Cathryn A. TI Design of composite scaffolds and three-dimensional shape analysis for tissue-engineered ear SO JOURNAL OF THE ROYAL SOCIETY INTERFACE LA English DT Article DE tissue engineering; ear reconstruction; three-dimensional shape analysis; bending moment ID AURICULAR RECONSTRUCTION; IN-VITRO; CARTILAGE; MODEL; AURICLE AB Engineered cartilage is a promising option for auricular reconstruction. We have previously demonstrated that a titanium wire framework within a composite collagen ear-shaped scaffold helped to maintain the gross dimensions of the engineered ear after implantation, resisting the deformation forces encountered during neocartilage maturation and wound healing. The ear geometry was redesigned to achieve a more accurate aesthetic result when implanted subcutaneously in a nude rat model. A non-invasive method was developed to assess size and shape changes of the engineered ear in three dimensions. Computer models of the titanium framework were obtained from CT scans before and after implantation. Several parameters were measured including the overall length, width and depth, the minimum intrahelical distance and overall curvature values for each beam section within the framework. Local curvature values were measured to gain understanding of the bending forces experienced by the framework structure in situ. Length and width changed by less than 2%, whereas the depth decreased by approximately 8% and the minimum intrahelical distance changed by approximately 12%. Overall curvature changes identified regions most susceptible to deformation. Eighty-nine per cent of local curvature measurements experienced a bending moment less than 50 mu N-m owing to deformation forces during implantation. These quantitative shape analysis results have identified opportunities to improve shape fidelity of engineered ear constructs. C1 [Cervantes, Thomas M.; Bassett, Erik K.; Tseng, Alan; Kimura, Anya; Vacanti, Joseph P.; Pomerantseva, Irina; Sundback, Cathryn A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Randolph, Mark A.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. [Gupta, Rajiv] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Roscioli, Nick] Kensey Nash Corp, Exton, PA USA. [Randolph, Mark A.; Vacanti, Joseph P.; Hadlock, Theresa A.; Pomerantseva, Irina; Sundback, Cathryn A.] Harvard Univ, Sch Med, Boston, MA USA. [Hadlock, Theresa A.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM jvacanti@partners.org FU Armed Forces Institute of Regenerative Medicine award [W81XWH-08-2-0034] FX This research was sponsored in part by the Armed Forces Institute of Regenerative Medicine award number W81XWH-08-2-0034. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. NR 26 TC 5 Z9 7 U1 1 U2 9 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 1742-5689 EI 1742-5662 J9 J R SOC INTERFACE JI J. R. Soc. Interface PD OCT 6 PY 2013 VL 10 IS 87 AR 20130413 DI 10.1098/rsif.2013.0413 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 298BG UT WOS:000330298300006 PM 23904585 ER PT J AU Lee, DY Wauquier, F Eid, AA Roman, LJ Ghosh-Choudhury, G Khazim, K Block, K Gorin, Y AF Lee, Doug-Yoon Wauquier, Fabien Eid, Assaad A. Roman, Linda J. Ghosh-Choudhury, Goutam Khazim, Khaled Block, Karen Gorin, Yves TI Nox4 NADPH Oxidase Mediates Peroxynitrite-dependent Uncoupling of Endothelial Nitric-oxide Synthase and Fibronectin Expression in Response to Angiotensin II ROLE OF MITOCHONDRIAL REACTIVE OXYGEN SPECIES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Angiotensin II; Extracellular Matrix Proteins; Kidney; Nitric-oxide Synthase; Nox; Oxidative Stress ID RAT MESANGIAL CELLS; EXPERIMENTAL DIABETIC-NEPHROPATHY; NAD(P)H OXIDASE; MOLECULAR-MECHANISMS; GLOMERULAR INJURY; RECEPTOR BLOCKADE; VASCULAR-DISEASE; REDOX CONTROL; UP-REGULATION; SUPEROXIDE AB Activation of glomerular mesangial cells (MCs) by angiotensin II (Ang II) leads to extracellular matrix accumulation. Here, we demonstrate that, in MCs, Ang II induces endothelial nitric-oxide synthase (eNOS) uncoupling with enhanced generation of reactive oxygen species (ROS) and decreased production of NO. Ang II promotes a rapid increase in 3-nitrotyrosine formation, and uric acid attenuates Ang II-induced decrease in NO bioavailability, demonstrating that peroxynitrite mediates the effects of Ang II on eNOS dysfunction. Ang II rapidly up-regulates Nox4 protein. Inhibition of Nox4 abolishes the increase in ROS and peroxynitrite generation as well as eNOS uncoupling triggered by Ang II, indicating that Nox4 is upstream of eNOS. This pathway contributes to Ang II-mediated fibronectin accumulation in MCs. Ang II also elicits an increase in mitochondrial abundance of Nox4 protein, and the oxidase contributes to ROS production in mitochondria. Overexpression of mitochondrial manganese superoxide dismutase prevents the stimulatory effects of Ang II on mitochondrial ROS production, loss of NO availability, and MC fibronectin accumulation, whereas manganese superoxide dismutase depletion increases mitochondrial ROS, NO deficiency, and fibronectin synthesis basally and in cells exposed to Ang II. This work provides the first evidence that uncoupled eNOS is responsible for Ang II-induced MC fibronectin accumulation and identifies Nox4 and mitochondrial ROS as mediators of eNOS dysfunction. These data shed light on molecular processes underlying the oxidative signaling cascade engaged by Ang II and identify potential targets for intervention to prevent renal fibrosis. C1 [Lee, Doug-Yoon; Wauquier, Fabien; Eid, Assaad A.; Ghosh-Choudhury, Goutam; Khazim, Khaled; Block, Karen; Gorin, Yves] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Roman, Linda J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Ghosh-Choudhury, Goutam] Vet Adm Res & Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. [Ghosh-Choudhury, Goutam; Block, Karen] South Texas Vet Hlth Care Syst, Audie Leon Murphy Mem Hosp Div, San Antonio, TX 78229 USA. RP Gorin, Y (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Nephrol MC 7882, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM gorin@uthscsa.edu FU National Institutes of Health [RO1 DK 079996, RO1 CA 131272, RO1 DK 50190]; Juvenile Diabetes Research Foundation Multiproject Grant; Juvenile Diabetes Research Foundation Advanced Research Fellowship Grant; Veterans Administration Merit Awards; Veterans Administration Senior Research Career Scientist Award FX This work was supported, in whole or in part, by National Institutes of Health Grants RO1 DK 079996 (to Y. G.), RO1 CA 131272 (to K. B.), and RO1 DK 50190 (to G. G. C.). This work was also supported in part by a Juvenile Diabetes Research Foundation Multiproject Grant (to Y. G. and K. B.), a Juvenile Diabetes Research Foundation Advanced Research Fellowship Grant (to A. A. E.), and Veterans Administration Merit Awards (to K. B. and G. G. C.).; Recipient of Veterans Administration Senior Research Career Scientist Award. NR 78 TC 44 Z9 45 U1 4 U2 14 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 OCT 4 PY 2013 VL 288 IS 40 BP 28668 EP 28686 DI 10.1074/jbc.M113.470971 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 298BL UT WOS:000330298800022 PM 23940049 ER PT J AU Armata, IA Balaj, L Kuster, JK Zhang, X Tsai, SL Armatas, AA Multhaupt-Buell, TJ Soberman, R Breakefield, XO Ichinose, H Sharma, N AF Armata, Ioanna A. Balaj, Leonora Kuster, John K. Zhang, Xuan Tsai, Shelun Armatas, Andreas A. Multhaupt-Buell, Trisha J. Soberman, Roy Breakefield, Xandra O. Ichinose, Hiroshi Sharma, Nutan TI Dopa-Responsive Dystonia: Functional Analysis of Single Nucleotide Substitutions within the 5 ' Untranslated GCH1 Region SO PLOS ONE LA English DT Article ID GTP CYCLOHYDROLASE-I; HEREDITARY PROGRESSIVE DYSTONIA; MARKED DIURNAL FLUCTUATION; TRANSLATION INITIATION; GENE-EXPRESSION; MUTATION; TETRAHYDROBIOPTERIN; METABOLISM; MECHANISMS; DISORDERS AB Background: Mutations in the GCH1 gene are associated with childhood onset, dopa-responsive dystonia (DRD). Correct diagnosis of DRD is crucial, given the potential for complete recovery once treated with L-dopa. The majority of DRD associated mutations lie within the coding region of the GCH1 gene, but three additional single nucleotide sequence substitutions have been reported within the 5' untranslated (5'UTR) region of the mRNA. The biologic significance of these 5' UTR GCH1 sequence substitutions has not been analyzed. Methodology/Principal Findings: Luciferase reporter assays, quantitative real time PCR and RNA decay assays, combined with bioinformatics, revealed a pathogenic 5' UTR GCH1 substitution. The +142C>T single nucleotide 5' UTR substitution that segregates with affected status in DRD patients, substantially attenuates translation without altering RNA expression levels or stability. The +142C>T substitution disrupts translation most likely by creating an upstream initiation start codon (uAUG) and an upstream open reading frame (uORF). Conclusions/Significance: This is the first GCH1 regulatory substitution reported to act at a post-transcriptional level, increasing the list of genetic diseases caused by abnormal translation and reaffirming the importance of investigating potential regulatory substitutions in genetic diseases. C1 [Armata, Ioanna A.; Balaj, Leonora; Kuster, John K.; Zhang, Xuan; Tsai, Shelun; Multhaupt-Buell, Trisha J.; Breakefield, Xandra O.; Sharma, Nutan] Massachusetts Gen Hosp, Dept Neurogenet, Boston, MA 02114 USA. [Armata, Ioanna A.; Balaj, Leonora; Kuster, John K.; Zhang, Xuan; Tsai, Shelun; Multhaupt-Buell, Trisha J.; Breakefield, Xandra O.; Sharma, Nutan] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Armatas, Andreas A.] Univ Patras, Dept Biol, Rion, Greece. [Soberman, Roy] Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. [Ichinose, Hiroshi] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Yokohama, Kanagawa 227, Japan. RP Armata, IA (reprint author), Massachusetts Gen Hosp, Dept Neurogenet, Boston, MA 02114 USA. EM ionarm999@gmail.com RI Ichinose, Hiroshi/D-8986-2015 OI Ichinose, Hiroshi/0000-0001-6008-6860 FU NIH/NINDS [5P50NS037409] FX This work was supported by NIH/NINDS 5P50NS037409 (XOB and NS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 0 Z9 1 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 4 PY 2013 VL 8 IS 10 AR e76975 DI 10.1371/journal.pone.0076975 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 232JF UT WOS:000325489100159 PM 24124602 ER PT J AU Ballandras-Colas, A Naraharisetty, H Li, X Serrao, E Engelman, A AF Ballandras-Colas, Allison Naraharisetty, Hema Li, Xiang Serrao, Erik Engelman, Alan TI Biochemical Characterization of Novel Retroviral Integrase Proteins SO PLOS ONE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1 DNA INTEGRATION; DERMAL SARCOMA-VIRUS; STRAND TRANSFER; NUCLEOTIDE-SEQUENCE; TARGET SITES; MECHANISM; CONSTRUCTION; REPLICATION; INHIBITION AB Integrase is an essential retroviral enzyme, catalyzing the stable integration of reverse transcribed DNA into cellular DNA. Several aspects of the integration mechanism, including the length of host DNA sequence duplication flanking the integrated provirus, which can be from 4 to 6 bp, and the nucleotide preferences at the site of integration, are thought to cluster among the different retroviral genera. To date only the spumavirus prototype foamy virus integrase has provided diffractable crystals of integrase-DNA complexes, revealing unprecedented details on the molecular mechanisms of DNA integration. Here, we characterize five previously unstudied integrase proteins, including those derived from the alpharetrovirus lymphoproliferative disease virus (LPDV), betaretroviruses Jaagsiekte sheep retrovirus (JSRV), and mouse mammary tumor virus (MMTV), epsilonretrovirus walleye dermal sarcoma virus (WDSV), and gammaretrovirus reticuloendotheliosis virus strain A (Rev-A) to identify potential novel structural biology candidates. Integrase expressed in bacterial cells was analyzed for solubility, stability during purification, and, once purified, 3' processing and DNA strand transfer activities in vitro. We show that while we were unable to extract or purify accountable amounts of WDSV, JRSV, or LPDV integrase, purified MMTV and Rev-A integrase each preferentially support the concerted integration of two viral DNA ends into target DNA. The sequencing of concerted Rev-A integration products indicates high fidelity cleavage of target DNA strands separated by 5 bp during integration, which contrasts with the 4 bp duplication generated by a separate gammaretrovirus, the Moloney murine leukemia virus (MLV). By comparing Rev-A in vitro integration sites to those generated by MLV in cells, we concordantly conclude that the spacing of target DNA cleavage is more evolutionarily flexible than are the target DNA base contacts made by integrase during integration. Given their desirable concerted DNA integration profiles, Rev-A and MMTV integrase proteins have been earmarked for structural biology studies. C1 [Engelman, Alan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Engelman, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu FU US National Institutes of Health [R01 AI070042, T32 AI007245] FX This work was supported by US National Institutes of Health grants R01 AI070042 and T32 AI007245. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 9 Z9 10 U1 0 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 OCT 4 PY 2013 VL 8 IS 10 AR e76638 DI 10.1371/journal.pone.0076638 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 232JF UT WOS:000325489100138 PM 24124581 ER PT J AU Kloverpris, HN Jackson, A Handley, A Hayes, P Gilmour, J Riddell, L Chen, FB Atkins, M Boffito, M Walker, BD Ackland, J Sullivan, M Goulder, P AF Kloverpris, Henrik N. Jackson, Akil Handley, Amanda Hayes, Peter Gilmour, Jill Riddell, Lynn Chen, Fabian Atkins, Mark Boffito, Marta Walker, Bruce D. Ackland, Jim Sullivan, Mark Goulder, Philip TI Non-Immunogenicity of Overlapping Gag Peptides Pulsed on Autologous Cells after Vaccination of HIV Infected Individuals SO PLOS ONE LA English DT Article ID IMMUNODEFICIENCY VIRUS SIVMAC239; T-CELLS; CLINICAL-TRIALS; DENDRITIC CELLS; CANDIDATE VACCINE; HEALTHY-ADULTS; PHASE-1 SAFETY; DNA VACCINE; RESPONSES; IMMUNITY AB Background: HIV Gag-specific CD4+ and CD8+ T-cell responses are important for HIV immune control. Pulsing overlapping Gag peptides on autologous lymphocytes (OPAL) has proven immunogenic and effective in reducing viral loads in multiple pigtail macaque studies, warranting clinical evaluation. Methodology: We performed a phase I, single centre, placebo-controlled, double-blinded and dose-escalating study to evaluate the safety and preliminary immunogenicity of a novel therapeutic vaccine approach 'OPAL-HIV-Gag(c)'. This vaccine is comprised of 120 15mer peptides, overlapping by 11 amino acids, spanning the HIV Gag C clade sequence proteome, pulsed on white blood cells enriched from whole blood using a closed system, followed by intravenous reinfusion. Patients with undetectable HIV viral loads (<50 copies/ml plasma) on HAART received four administrations at week 0, 4, 8 and 12, and were followed up for 12 weeks post-treatment. Twenty-three people were enrolled in four groups: 12 mg (n = 6), 24 mg (n = 7), 48 mg (n = 2) or matching placebo (n = 8) with 18 immunologically evaluable. T-cell immunogenicity was assessed by IFN gamma ELIspot and intracellular cytokine staining (ICS). Results: The OPAL-HIV-Gag(c) peptides were antigenic in vitro in 17/17 subjects. After vaccination with OPAL-HIV-Gag(c), 1/6 subjects at 12 mg and 1/6 subjects at 24 mg dose groups had a 2- and 3-fold increase in ELIspot magnitudes from baseline, respectively, of Gag-specific CD8+ T-cells at week 14, compared to 0/6 subjects in the placebo group. No Gag-specific CD4+ T-cell responses or overall change in Rev, Nef, Tat and CMV specific responses were detected. Marked, transient and self-limiting lymphopenia was observed immediately post-vaccination (4 hours) in OPAL-HIV-Gag(c) but not in placebo recipients, with median fall from 1.72 to 0.67 million lymphocytes/mL for active groups (P<0.001), compared to post-placebo from 1.70 to 1.56 lymphocytes/ml (P = 0.16). Conclusion/Significance: Despite strong immunogenicity observed in several Macaca nemestrina studies using this approach, OPAL-HIV-Gag(c) was not significantly immunogenic in humans and improved methods of generating high-frequency Gag-specific T-cell responses are required. C1 [Kloverpris, Henrik N.; Goulder, Philip] Univ Oxford, Dept Paediat, Oxford, England. [Jackson, Akil; Boffito, Marta] Chelsea & Westminster Hosp, St Stephens AIDS Trust St Stephens Ctr, London, England. [Handley, Amanda; Sullivan, Mark] Med Dev, Melbourne, Vic, Australia. [Hayes, Peter; Gilmour, Jill; Atkins, Mark] Univ London Imperial Coll Sci Technol & Med, IAVI Human Immunol Lab, London, England. [Riddell, Lynn] Northhamptonshire Healthcare Natl Hlth Serv Trust, Northhampton Gen Hosp, Dept Genitourinary Med, Cliftonville, Northhampton, England. [Chen, Fabian] Royal Berkshire Hosp, Dept Sexual Hlth, Reading RG1 5AN, Berks, England. [Kloverpris, Henrik N.] Univ Kwazulu Natal, Nelson R Mandela Sch Med, KwaZulu Natal Res Inst TB & HIV K RITH, Durban, KwaZulu Natal, South Africa. [Kloverpris, Henrik N.] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark. [Walker, Bruce D.; Goulder, Philip] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Ackland, Jim] Global Biosolut, Craigeburn, Vic, Australia. RP Kloverpris, HN (reprint author), Univ Oxford, Dept Paediat, Oxford, England. EM henrik.kloverpris@k-rith.org FU Phillip T; Susan M Ragon Foundation FX The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funding for this project was provided by the Phillip T and Susan M Ragon Foundation. Medicines Development was a study Sponsor, as defined in the US Code of Federal Regulations, Title 21, Chapter I, Subchapter D, Subpart D, Part 312.50. NR 44 TC 0 Z9 0 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 4 PY 2013 VL 8 IS 10 AR e74389 DI 10.1371/journal.pone.0074389 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 232JF UT WOS:000325489100008 PM 24124451 ER PT J AU Lin, G Field, JJ Yu, JC Ken, R Neuberg, D Nathan, DG Linden, J AF Lin, Gene Field, Joshua J. Yu, Jennifer C. Ken, Ruey Neuberg, Donna Nathan, David G. Linden, Joel TI NF-kappa B Is Activated in CD4(+) iNKT Cells by Sickle Cell Disease and Mediates Rapid Induction of Adenosine A(2A) Receptors SO PLOS ONE LA English DT Article ID KILLER T-CELLS; ISCHEMIA-REPERFUSION INJURY; IFN-GAMMA PRODUCTION; NKT CELLS; INVARIANT NKT; VASCULAR INFLAMMATION; MURINE; MICE; VASOOCCLUSION; LOCALIZATION AB Reperfusion injury following tissue ischemia occurs as a consequence of vaso-occlusion that is initiated by activation of invariant natural killer T (iNKT) cells. Sickle cell disease (SDC) results in widely disseminated microvascular ischemia and reperfusion injury as a result of vaso-occlusion by rigid and adhesive sickle red blood cells. In mice, iNKT cell activation requires NF-kappa B signaling and can be inhibited by the activation of anti-inflammatory adenosine A(2A) receptors (A(2A)Rs). Human iNKT cells are divided into subsets of CD4+ and CD4- cells. In this study we found that human CD4+ iNKT cells, but not CD4- cells undergo rapid NF-kappa B activation (phosphorylation of NF-kappa B on p65) and induction of A(2A)Rs (detected with a monoclonal antibody 7F6-G5-A2) during SCD painful vaso-occlusive crises. These findings indicate that SCD primarily activates the CD4+ subset of iNKT cells. Activation of NF-kappa B and induction of A(2A)Rs is concordant, i.e. only CD4+ iNKT cells with activated NF-kappa B expressed high levels of A(2A)Rs. iNKT cells that are not activated during pVOC express low levels of A(2A)R immunoreactivity. These finding suggest that A(2A)R transcription may be induced in CD4+ iNKT cells as a result of NFkB activation in SCD. In order to test this hypothesis further we examined cultured human iNKT cells. In cultured cells, blockade of NF-kappa B with Bay 11-7082 or IKK inhibitor VII prevented rapid induction of A(2A)R mRNA and protein upon iNKT activation. In conclusion, NF-kappa B-mediated induction of A(2A)Rs in iNKT cells may serve as a counter-regulatory mechanism to limit the extent and duration of inflammatory immune responses. As activated iNKT cells express high levels of A(2A)Rs following their activation, they may become highly sensitive to inhibition by A(2A)R agonists. C1 [Lin, Gene; Yu, Jennifer C.; Ken, Ruey; Linden, Joel] La Jolla Inst Allergy & Immunol, Div Inflammat Biol, La Jolla, CA USA. [Field, Joshua J.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Neuberg, Donna; Nathan, David G.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Linden, J (reprint author), La Jolla Inst Allergy & Immunol, Div Inflammat Biol, La Jolla, CA USA. EM jlinden@liai.org RI Linden, Joel/J-9259-2014 OI Linden, Joel/0000-0002-0689-1647 FU National Institutes of Health [RC2 HL101367, R34 HL108757, R01HL095704] FX Supported by grants RC2 HL101367, R34 HL108757 and R01HL095704 from the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 13 Z9 13 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 OCT 4 PY 2013 VL 8 IS 10 AR e74664 DI 10.1371/journal.pone.0074664 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 232JF UT WOS:000325489100010 PM 24124453 ER PT J AU Wang, HY Meyer, CA Fei, T Wang, G Zhang, F Liu, XS AF Wang, Haiyun Meyer, Clifford A. Fei, Teng Wang, Gang Zhang, Fan Liu, X. Shirley TI A systematic approach identifies FOXA1 as a key factor in the loss of epithelial traits during the epithelial-to-mesenchymal transition in lung cancer SO BMC GENOMICS LA English DT Article DE The epithelial-to-mesenchymal transition; Lung cancer; ChIP-Seq; FOXA1 ID TUMOR-METASTASIS; E-CADHERIN; TRANSCRIPTION FACTORS; CELLS; GENE; DIFFERENTIATION; REGULATOR; RECEPTOR; POLARITY; GENOME AB Background: The epithelial-to-mesenchymal transition is an important mechanism in cancer metastasis. Although transcription factors including SNAIL, SLUG, and TWIST1 regulate the epithelial-to-mesenchymal transition, other unknown transcription factors could also be involved. Identification of the full complement of transcription factors is essential for a more complete understanding of gene regulation in this process. Chromatin immunoprecipitation-sequencing (ChIP-Seq) technologies have been used to detect genome-wide binding of transcription factors; here, we developed a systematic approach to integrate existing ChIP-Seq and transcriptome data. We scanned multiple transcription factors to investigate their functional impact on the epithelial-to-mesenchymal transition in the human A549 lung adenocarcinoma cell line. Results: Among the transcription factors tested, impact scores identified the forkhead box protein A1 (FOXA1) as the most significant transcription factor in the epithelial-to-mesenchymal transition. FOXA1 physically associates with the promoters of its predicted target genes. Several critical epithelial-to-mesenchymal transition effectors involved in cellular adhesion and cellular communication were identified in the regulatory network of FOXA1, including FOXA2, FGA, FGB, FGG, and FGL1. The implication of FOXA1 in the epithelial-to-mesenchymal transition via its regulatory network indicates that FOXA1 may play an important role in the initiation of lung cancer metastasis. Conclusions: We identified FOXA1 as a potentially important transcription factor and negative regulator in the initial stages of lung cancer metastasis. FOXA1 may modulate the epithelial-to-mesenchymal transition via its transcriptional regulatory network. Further, this study demonstrates how ChIP-Seq and expression data could be integrated to delineate the impact of transcription factors on a specific biological process. C1 [Wang, Haiyun] Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China. [Wang, Haiyun; Meyer, Clifford A.; Fei, Teng; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Wang, Haiyun; Meyer, Clifford A.; Fei, Teng; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Wang, Haiyun] Tongji Univ, Adv Inst Translat Med, Shanghai 200092, Peoples R China. [Fei, Teng] Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02215 USA. [Fei, Teng] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Wang, Gang; Zhang, Fan] Tongji Univ, Sch Life Sci & Technol, Shanghai Pulm Hosp, Clin Translat Res Ctr, Shanghai 200092, Peoples R China. RP Wang, HY (reprint author), Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China. EM wanghaiyun@tongji.edu.cn; fzhang@tongji.edu.cn RI Fei, Teng/G-5324-2015 OI Fei, Teng/0000-0001-5707-0673 FU National Natural Science Foundation of China [31100912, 31329003]; National Institutes of Health [HG4069] FX This work was supported by National Natural Science Foundation of China (31100912); National Natural Science Foundation of China (31329003); and National Institutes of Health (HG4069). NR 33 TC 9 Z9 10 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD OCT 4 PY 2013 VL 14 AR 680 DI 10.1186/1471-2164-14-680 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 241NQ UT WOS:000326174300002 PM 24093963 ER PT J AU Widge, A AF Widge, Alik TI NextGen Speaks SO SCIENCE LA English DT Letter C1 [Widge, Alik] Massachusetts Gen Hosp, Dept Psychiat, Div Neurotherapeut, Charlestown, MA 02129 USA. [Widge, Alik] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. RP Widge, A (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Div Neurotherapeut, Charlestown, MA 02129 USA. EM awidge@mit.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 4 PY 2013 VL 342 IS 6154 BP 37 EP 37 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 227PP UT WOS:000325126100020 ER PT J AU Khurana, E Fu, Y Colonna, V Mu, XJ Kang, HM Lappalainen, T Sboner, A Lochovsky, L Chen, JM Harmanci, A Das, J Abyzov, A Balasubramanian, S Beal, K Chakravarty, D Challis, D Chen, Y Clarke, D Clarke, L Cunningham, F Evani, US Flicek, P Fragoza, R Garrison, E Gibbs, R Guemues, ZH Herrero, J Kitabayashi, N Kong, Y Lage, K Liluashvili, V Lipkin, SM MacArthur, DG Marth, G Muzny, D Pers, TH Ritchie, GRS Rosenfeld, JA Sisu, C Wei, XM Wilson, M Xue, YL Yu, FL Dermitzakis, ET Yu, HY Rubin, MA Tyler-Smith, C Gerstein, M AF Khurana, Ekta Fu, Yao Colonna, Vincenza Mu, Xinmeng Jasmine Kang, Hyun Min Lappalainen, Tuuli Sboner, Andrea Lochovsky, Lucas Chen, Jieming Harmanci, Arif Das, Jishnu Abyzov, Alexej Balasubramanian, Suganthi Beal, Kathryn Chakravarty, Dimple Challis, Daniel Chen, Yuan Clarke, Declan Clarke, Laura Cunningham, Fiona Evani, Uday S. Flicek, Paul Fragoza, Robert Garrison, Erik Gibbs, Richard Guemues, Zeynep H. Herrero, Javier Kitabayashi, Naoki Kong, Yong Lage, Kasper Liluashvili, Vaja Lipkin, Steven M. MacArthur, Daniel G. Marth, Gabor Muzny, Donna Pers, Tune H. Ritchie, Graham R. S. Rosenfeld, Jeffrey A. Sisu, Cristina Wei, Xiaomu Wilson, Michael Xue, Yali Yu, Fuli Dermitzakis, Emmanouil T. Yu, Haiyuan Rubin, Mark A. Tyler-Smith, Chris Gerstein, Mark CA 1000 Genomes Project Consortium TI Integrative Annotation of Variants from 1092 Humans: Application to Cancer Genomics SO SCIENCE LA English DT Article ID TERT PROMOTER MUTATIONS; NATURAL-SELECTION; PROSTATE-CANCER; POSITIVE SELECTION; GENETIC-VARIATION; HUMAN-EVOLUTION; COPY NUMBER; ELEMENTS; NETWORK; DISEASE AB Interpreting variants, especially noncoding ones, in the increasing number of personal genomes is challenging. We used patterns of polymorphisms in functionally annotated regions in 1092 humans to identify deleterious variants; then we experimentally validated candidates. We analyzed both coding and noncoding regions, with the former corroborating the latter. We found regions particularly sensitive to mutations ("ultrasensitive") and variants that are disruptive because of mechanistic effects on transcription-factor binding (that is, "motif-breakers"). We also found variants in regions with higher network centrality tend to be deleterious. Insertions and deletions followed a similar pattern to single-nucleotide variants, with some notable exceptions (e. g., certain deletions and enhancers). On the basis of these patterns, we developed a computational tool (FunSeq), whose application to similar to 90 cancer genomes reveals nearly a hundred candidate noncoding drivers. C1 [Khurana, Ekta; Fu, Yao; Mu, Xinmeng Jasmine; Lochovsky, Lucas; Chen, Jieming; Harmanci, Arif; Abyzov, Alexej; Balasubramanian, Suganthi; Sisu, Cristina; Wilson, Michael; Gerstein, Mark] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA. [Khurana, Ekta; Harmanci, Arif; Abyzov, Alexej; Balasubramanian, Suganthi; Kong, Yong; Sisu, Cristina; Gerstein, Mark] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. [Colonna, Vincenza; Chen, Yuan; Xue, Yali; Tyler-Smith, Chris] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Colonna, Vincenza] CNR, Inst Genet & Biophys, I-80131 Naples, Italy. [Kang, Hyun Min] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Lappalainen, Tuuli; Dermitzakis, Emmanouil T.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Lappalainen, Tuuli; Dermitzakis, Emmanouil T.] Univ Geneva, iGE3, CH-1211 Geneva, Switzerland. [Lappalainen, Tuuli; Dermitzakis, Emmanouil T.] Swiss Inst Bioinformat, CH-1211 Geneva, Switzerland. [Sboner, Andrea; Chakravarty, Dimple; Kitabayashi, Naoki; Rubin, Mark A.] Weill Cornell Med Coll, Inst Precis Med, New York, NY 10065 USA. [Sboner, Andrea; Chakravarty, Dimple; Kitabayashi, Naoki; Rubin, Mark A.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA. New York Presbyterian Hosp, New York, NY 10065 USA. [Sboner, Andrea; Guemues, Zeynep H.; Liluashvili, Vaja] Weill Cornell Med Coll, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10021 USA. [Chen, Jieming] Yale Univ, Integrated Grad Program Phys & Engn Biol, New Haven, CT 06520 USA. [Das, Jishnu; Yu, Haiyuan] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA. [Das, Jishnu; Fragoza, Robert; Wei, Xiaomu; Yu, Haiyuan] Cornell Univ, Inst Cell & Mol Biol, Ithaca, NY 14853 USA. [Beal, Kathryn; Clarke, Laura; Cunningham, Fiona; Flicek, Paul; Herrero, Javier; Ritchie, Graham R. S.] European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England. [Challis, Daniel; Evani, Uday S.; Gibbs, Richard; Muzny, Donna; Yu, Fuli] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Clarke, Declan] Yale Univ, Dept Chem, New Haven, CT 06520 USA. [Fragoza, Robert] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. [Garrison, Erik; Marth, Gabor] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. [Guemues, Zeynep H.; Liluashvili, Vaja] Weill Cornell Med ical Coll, Dept Physiol & Biophys, New York, NY 10065 USA. [Kong, Yong] Yale Univ, Keck Biotechnol Resource Lab, New Haven, CT 06511 USA. [Lage, Kasper] Massachusetts Gen Hosp, MassGeneral Hosp Children, Pediat Surg Res Labs, Boston, MA 02114 USA. [Lage, Kasper; MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Lage, Kasper] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lage, Kasper; Pers, Tune H.] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Lage, Kasper] Univ Copenhagen, Ctr Prot Res, Copenhagen, Denmark. [Lipkin, Steven M.; Wei, Xiaomu] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA. [MacArthur, Daniel G.] Broad Inst Harvard & Massachusetts Inst Technol M, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Pers, Tune H.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Pers, Tune H.] Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA. [Pers, Tune H.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Rosenfeld, Jeffrey A.] Rutgers New Jersey Med Sch, Dept Med, Newark, NJ 07101 USA. [Rosenfeld, Jeffrey A.] Rutgers State Univ, IST High Performance & Res Comp, Newark, NJ 07101 USA. [Rosenfeld, Jeffrey A.] Amer Museum Nat Hist, Sackler Inst Comparat Genom, New York, NY 10024 USA. [Wilson, Michael] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. [Gerstein, Mark] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA. RP Tyler-Smith, C (reprint author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England. EM cts@sanger.ac.uk; mark.gerstein@yale.edu RI Abyzov, Alexej/M-4284-2013; Sboner, Andrea/C-6487-2008; Altshuler, David/A-4476-2009; Ye, Kai/B-3640-2012; Chakravarty, Dimple/N-3325-2014; Das, Jishnu/C-6924-2015; Browning, Brian/A-1178-2010; Li, Yingrui/K-1064-2015; Angius, Andrea/P-9549-2015; Mu, Xinmeng/P-2562-2016; Colonna, Vincenza/H-2021-2014; OI Sboner, Andrea/0000-0001-6915-3070; Altshuler, David/0000-0002-7250-4107; Chakravarty, Dimple/0000-0002-8588-8461; Das, Jishnu/0000-0002-5747-064X; Browning, Brian/0000-0001-6454-6633; Angius, Andrea/0000-0003-2596-6461; Mu, Xinmeng/0000-0002-8079-0828; Streeter, Ian/0000-0003-4024-3552; Angius, Andrea/0000-0001-9372-1162; Kulesha, Eugene/0000-0002-4285-6232; Colonna, Vincenza/0000-0002-3966-0474; Kim, Kicheol/0000-0003-3667-9900; Walter, Klaudia/0000-0003-4448-0301; Herrero, Javier/0000-0001-7313-717X; Rubin, Mark/0000-0002-8321-9950; Clarke, Laura/0000-0002-5989-6898; Cooper, David N./0000-0002-8943-8484; Flicek, Paul/0000-0002-3897-7955; McLaren, William/0000-0001-6218-1116; Keane, Thomas/0000-0001-7532-6898; Ritchie, Graham/0000-0002-6456-9736; Radhakrishnan, Rajesh/0000-0001-7170-699X; Sisu, Cristina/0000-0001-9371-0797; Abyzov, Alexej/0000-0001-5405-6729; Leinonen, Rasko/0000-0002-2639-7187; Rodriguez-Flores, Juan L/0000-0002-0394-8062; Lappalainen, Tuuli/0000-0002-7746-8109; Chen, Jieming/0000-0003-3767-9486; Sebat, Jonathan/0000-0002-9087-526X; Kong, Yong/0000-0002-2881-5274; Fuchsberger, Christian/0000-0002-5918-8947 FU Danish Council for Independent Research Medical Sciences; European Molecular Biology Laboratory; Wellcome Trust [WT085532, WT095908]; Wellcome-Trust Sanger Institute [098051]; National Cancer Institute (NCI) [R01CA152057]; Early Detection Research Network NCI [U01 CA111275]; Prostate Cancer Foundation [HG005718, HG007000]; National Human Genome Research Institute [R01HG4719, U01HG6513]; National Institute of General Medical Sciences [GM104424] FX We thank G. Boysen and C. O'Reilly for help with SNV experimental validation, K. Yip for target-gene identification, and Z. Liu for Web site design. T. H. P. is supported by the Danish Council for Independent Research Medical Sciences (FSS). Funding at the European Bioinformatics Institute is provided by European Molecular Biology Laboratory and the Wellcome Trust (WT085532 and WT095908). C.T.-S. acknowledges grant 098051 from the Wellcome-Trust Sanger Institute. Funding for the Institute for Precision Medicine (Weill Cornell Medical College/New York Presbyterian) is provided by National Cancer Institute (NCI) grant R01CA152057 (A. S., M. G., and M. A. R.) and Early Detection Research Network NCI U01 CA111275 (M. A. R.). M. A. R. also thanks the Prostate Cancer Foundation. M. G. also acknowledges grants HG005718 and HG007000. G. M. acknowledges National Human Genome Research Institute grants R01HG4719 and U01HG6513. H.Y. and S. M. L. are supported by NCI grant CA167824, National Institute of General Medical Sciences grant GM104424, and a Clinical and Translational Science Center Pilot Award and Cornell Seed Grant for intercampus collaborations. H. M. K., T. L., A. S., L. L., J.C., A. H., and J.D. contributed equally. NR 48 TC 140 Z9 146 U1 7 U2 66 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD OCT 4 PY 2013 VL 342 IS 6154 BP 84 EP + AR 1235587 DI 10.1126/science.1235587 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 227PP UT WOS:000325126100049 PM 24092746 ER PT J AU Wang, DS Song, CM Barabasi, AL AF Wang, Dashun Song, Chaoming Barabasi, Albert-Laszlo TI Quantifying Long-Term Scientific Impact SO SCIENCE LA English DT Article ID CITATION; NETWORKS; JOURNALS; SCIENCE; INDEX AB The lack of predictability of citation-based measures frequently used to gauge impact, from impact factors to short-term citations, raises a fundamental question: Is there long-term predictability in citation patterns? Here, we derive a mechanistic model for the citation dynamics of individual papers, allowing us to collapse the citation histories of papers from different journals and disciplines into a single curve, indicating that all papers tend to follow the same universal temporal pattern. The observed patterns not only help us uncover basic mechanisms that govern scientific impact but also offer reliable measures of influence that may have potential policy implications. C1 [Wang, Dashun; Song, Chaoming; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Biol, Dept Phys, Ctr Complex Network Res, Boston, MA 02115 USA. [Wang, Dashun; Song, Chaoming; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Comp Sci, Boston, MA 02115 USA. [Wang, Dashun] IBM Thomas J Watson Res Ctr, Yorktown Hts, NY 10598 USA. [Song, Chaoming] Univ Miami, Dept Phys, Coral Gables, FL 33124 USA. [Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Cent European Univ, Ctr Network Sci, Budapest, Hungary. RP Barabasi, AL (reprint author), Northeastern Univ, Dept Biol, Dept Phys, Ctr Complex Network Res, Boston, MA 02115 USA. EM alb@neu.edu FU Lockheed Martin Corporation [SRA 11.18.11]; Network Science Collaborative Technology Alliance; U.S. Army Research Laboratory [W911NF-09-2-0053]; Defense Advanced Research Projects Agency [11645021]; Future and Emerging Technologies Project [317 532]; European Commission FX The authors thank P. Azoulay, C. Hidalgo, J. Loscalzo, D. Pedreschi, B. Uzzi, M. Vidal, and members of Center for Complex Network Research for insightful discussions and the anonymous referee for suggesting the lognormal model, which led to the analytical prediction of the citation threshold for preferential attachment. The PR data set is available upon request through American Physical Society. Supported by Lockheed Martin Corporation (SRA 11.18.11), the Network Science Collaborative Technology Alliance is sponsored by the U.S. Army Research Laboratory under agreement W911NF-09-2-0053, Defense Advanced Research Projects Agency under agreement 11645021, and the Future and Emerging Technologies Project 317 532 "Multiplex" financed by the European Commission. NR 30 TC 115 Z9 119 U1 16 U2 154 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 4 PY 2013 VL 342 IS 6154 BP 127 EP 132 DI 10.1126/science.1237825 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 227PP UT WOS:000325126100061 PM 24092745 ER PT J AU Liu, XH Ide, JL Norton, I Marchionni, MA Ebling, MC Wang, LY Davis, E Sauvageot, CM Kesari, S Kellersberger, KA Easterling, ML Santagata, S Stuart, DD Alberta, J Agar, JN Stiles, CD Agar, NYR AF Liu, Xiaohui Ide, Jennifer L. Norton, Isaiah Marchionni, Mark A. Ebling, Maritza C. Wang, Lan Y. Davis, Erin Sauvageot, Claire M. Kesari, Santosh Kellersberger, Katherine A. Easterling, Michael L. Santagata, Sandro Stuart, Darrin D. Alberta, John Agar, Jeffrey N. Stiles, Charles D. Agar, Nathalie Y. R. TI Molecular imaging of drug transit through the blood-brain barrier with MALDI mass spectrometry imaging SO SCIENTIFIC REPORTS LA English DT Article ID GROWTH-FACTOR RECEPTOR; TISSUE-SECTIONS; ERLOTINIB; PATHWAY; CELL; AUTORADIOGRAPHY; INHIBITOR; DISCOVERY; CANCER; OPTIMIZATION AB Drug transit through the blood-brain barrier (BBB) is essential for therapeutic responses in malignant glioma. Conventional methods for assessment of BBB penetrance require synthesis of isotopically labeled drug derivatives. Here, we report a new methodology using matrix assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) to visualize drug penetration in brain tissue without molecular labeling. In studies summarized here, we first validate heme as a simple and robust MALDI MSI marker for the lumen of blood vessels in the brain. We go on to provide three examples of how MALDI MSI can provide chemical and biological insights into BBB penetrance and metabolism of small molecule signal transduction inhibitors in the brain - insights that would be difficult or impossible to extract by use of radiolabeled compounds. C1 [Liu, Xiaohui; Ide, Jennifer L.; Norton, Isaiah; Ebling, Maritza C.; Agar, Nathalie Y. R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. [Marchionni, Mark A.; Wang, Lan Y.; Davis, Erin; Sauvageot, Claire M.; Alberta, John; Stiles, Charles D.; Agar, Nathalie Y. R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Kesari, Santosh] Univ Calif San Diego, La Jolla, CA 92093 USA. [Kellersberger, Katherine A.; Easterling, Michael L.] Bruker Daltonics Inc, Billerica, MA USA. [Santagata, Sandro] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Stuart, Darrin D.] Novartis Inst BioMed Res, Emeryville, CA USA. [Agar, Jeffrey N.] Brandeis Univ, Waltham, MA USA. [Agar, Nathalie Y. R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Agar, NYR (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. EM Charles_Stiles@dfci.harvard.edu; Nathalie_Agar@dfci.harvard.edu RI Kesari, Santosh/E-8461-2013 FU US National Institute of Health (NIH) [1DP2OD007383-01]; NIH-NCI [P01 CA142536]; Pediatric Low Grade Astrocytoma Program at Dana-Farber Cancer Institute; Brain Science Foundation; Daniel E. Ponton fund for the Neurosciences at BWH; Dana-Farber/Novartis Program in Drug Discovery; Amyotrophic Lateral Sclerosis Association [1856] FX This work was funded in part by US National Institute of Health (NIH) Director's New Innovator Award (1DP2OD007383-01 to N.Y.R.A.), and the NIH-NCI (P01 CA142536 to C. D. S. and N.Y.R.A.). The work received support from the Pediatric Low Grade Astrocytoma Program at Dana-Farber Cancer Institute, the Brain Science Foundation and the Daniel E. Ponton fund for the Neurosciences at BWH and the Dana-Farber/Novartis Program in Drug Discovery. J.N.A. received support from the Amyotrophic Lateral Sclerosis Association grant number 1856. We thank Daniel Feldman for his assistance with the tandem MS experiments. NR 38 TC 36 Z9 37 U1 4 U2 38 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD OCT 4 PY 2013 VL 3 AR 2859 DI 10.1038/srep02859 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 228UH UT WOS:000325216000006 PM 24091529 ER PT J AU Brumbaugh, J Hochedlinger, K AF Brumbaugh, Justin Hochedlinger, Konrad TI Removing Reprogramming Roadblocks: Mbd3 Depletion Allows Deterministic iPSC Generation SO CELL STEM CELL LA English DT Editorial Material ID PLURIPOTENT STEM-CELLS; SOMATIC-CELLS AB Transcription factor-induced pluripotency is extremely inefficient and assumed to be stochastic. In a recent Nature publication, Rais et al. show that depletion of the methyl-binding protein 3 yields reprogramming efficiencies of up to 100% within days, suggesting that elimination of a single gene suffices to render reprogramming a deterministic process. C1 [Brumbaugh, Justin; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Brumbaugh, Justin; Hochedlinger, Konrad] Ctr Regenerat Med, Boston, MA 02114 USA. [Brumbaugh, Justin; Hochedlinger, Konrad] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Hochedlinger, Konrad] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Hochedlinger, Konrad] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Hochedlinger, K (reprint author), Massachusetts Gen Hosp, Ctr Canc, 185 Cambridge St, Boston, MA 02114 USA. EM khochedlinger@helix.mgh.harvard.edu NR 9 TC 5 Z9 6 U1 0 U2 9 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 OCT 3 PY 2013 VL 13 IS 4 BP 379 EP 381 DI 10.1016/j.stem.2013.09.012 PG 3 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 287VT UT WOS:000329571100005 PM 24094318 ER PT J AU Doulatov, S Vo, LT Chou, SS Kim, PG Arora, N Li, H Hadland, BK Bernstein, ID Collins, JJ Zon, LI Daley, GQ AF Doulatov, Sergei Vo, Linda T. Chou, Stephanie S. Kim, Peter G. Arora, Natasha Li, Hu Hadland, Brandon K. Bernstein, Irwin D. Collins, James J. Zon, Leonard I. Daley, George Q. TI Induction of Multipotential Hematopoietic Progenitors from Human Pluripotent Stem Cells via Respecification of Lineage-Restricted Precursors SO CELL STEM CELL LA English DT Article ID RED-BLOOD-CELLS; IN-VIVO; DIFFERENTIATION CULTURES; REPOPULATING ABILITY; AORTIC ENDOTHELIUM; GENERATION; EXPRESSION; MACROPHAGES; TRANSFUSION; ENGRAFTMENT AB Human pluripotent stem cells (hPSCs) represent a promising source of patient-specific cells for disease modeling, drug screens, and cellular therapies. However, the inability to derive engraftable human hematopoietic stem and progenitor cells (HSPCs) has limited their characterization to in vitro assays. We report a strategy to respecify lineage-restricted CD34(+)CD45(+) myeloid precursors derived from hPSCs into multilineage progenitors that can be expanded in vitro and engrafted in vivo. HOXA9, ERG, and RORA conferred self-renewal and multilineage potential in vitro and maintained primitive CD34(+)CD38(-) cells. Screening cells via transplantation revealed that two additional factors, SOX4 and MYB, conferred engraftment. Progenitors specified with all five factors gave rise to reproducible short-term engraftment with myeloid and erythroid lineages. Erythroid precursors underwent hemoglobin switching in vivo, silencing embryonic and activating adult globin expression. Our combinatorial screening approach establishes a strategy for obtaining transcription-factor-mediated engraftment of blood progenitors from human pluripotent cells. C1 [Doulatov, Sergei; Vo, Linda T.; Chou, Stephanie S.; Kim, Peter G.; Arora, Natasha; Daley, George Q.] Childrens Hosp, Howard Hughes Med Inst, Stem Cell Transplantat Program, Div Pediat Hematol Oncol,Manton Ctr Orphan Dis Re, Boston, MA 02115 USA. [Doulatov, Sergei; Vo, Linda T.; Chou, Stephanie S.; Kim, Peter G.; Arora, Natasha; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Doulatov, Sergei; Vo, Linda T.; Chou, Stephanie S.; Kim, Peter G.; Arora, Natasha; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Doulatov, Sergei; Vo, Linda T.; Chou, Stephanie S.; Kim, Peter G.; Arora, Natasha; Zon, Leonard I.; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Li, Hu; Collins, James J.] Boston Univ, Howard Hughes Med Inst, Dept Biomed Engn, Boston, MA 02215 USA. [Li, Hu; Collins, James J.] Boston Univ, Ctr BioDynam, Boston, MA 02215 USA. [Li, Hu; Collins, James J.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Hadland, Brandon K.; Bernstein, Irwin D.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Hadland, Brandon K.; Bernstein, Irwin D.] Univ Washington, Dept Pediat, Seattle, WA 98105 USA. [Zon, Leonard I.] Childrens Hosp, Howard Hughes Med Inst, Div Pediat Hematol Oncol, Stem Cell Program, Boston, MA 02115 USA. [Zon, Leonard I.; Daley, George Q.] Broad Inst, Cambridge, MA 02141 USA. RP Daley, GQ (reprint author), Childrens Hosp, Howard Hughes Med Inst, Stem Cell Transplantat Program, Div Pediat Hematol Oncol,Manton Ctr Orphan Dis Re, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu FU US National Institute of Diabetes and Digestive and Kidney Diseases [R24-DK092760]; National Heart, Lung, Blood Institute Progenitor Cell Biology Consortium [UO1-HL100001]; Alex's Lemonade Stand; Doris Duke Medical Foundation; Helen Hay Whitney Foundation; NSF FX The authors would like to thank Thorsten Schlaeger and the BCH ESC core, Ronald Mathieu from the flow cytometry core, and Norman Gerry from the Coriell Genotyping and Microarray Center for assistance. Andrea Ditadi and Gordon Keller provided reagents and advice. Band3 antibody was a gift from the Narla Mohandas lab. This work is supported by grants from the US National Institute of Diabetes and Digestive and Kidney Diseases (R24-DK092760) and the National Heart, Lung, Blood Institute Progenitor Cell Biology Consortium (UO1-HL100001); Alex's Lemonade Stand; and the Doris Duke Medical Foundation. G. Q. D. is an associate member of the Broad Institute and an investigator of the Howard Hughes Medical Institute and the Manton Center for Orphan Disease Research. S. D. is supported by a fellowship from the Helen Hay Whitney Foundation. L. T. V. is supported by the NSF Graduate Research Fellowship. NR 47 TC 72 Z9 72 U1 4 U2 20 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 OCT 3 PY 2013 VL 13 IS 4 BP 459 EP 470 DI 10.1016/j.stem.2013.09.002 PG 12 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 287VT UT WOS:000329571100014 PM 24094326 ER PT J AU Liu, JC Guan, X Ryan, JA Rivera, AG Mock, C Agarwal, V Letai, A Lerou, PH Lahav, G AF Liu, Julia C. Guan, Xiao Ryan, Jeremy A. Rivera, Ana G. Mock, Caroline Agarwal, Vishesh Letai, Anthony Lerou, Paul H. Lahav, Galit TI High Mitochondrial Priming Sensitizes hESCs to DNA-Damage-Induced Apoptosis SO CELL STEM CELL LA English DT Article ID EMBRYONIC STEM-CELLS; BCL-2 FAMILY; SELF-RENEWAL; IN-VIVO; P53; DIFFERENTIATION; PUMA; ACTIVATION; EXPRESSION; RADIATION AB Human embryonic stem cells (hESCs) are highly sensitive to DNA damage and have low survival ability relative to differentiated cells. We investigated the source of this difference by comparing damage response pathways in hESCs and differentiated cells. We found that hESCs undergo more rapid p53-dependent apoptosis after DNA damage than differentiated cells do. However, p53 localization and function are similar between hESCs and differentiated cells, suggesting that p53 alone cannot explain the difference in sensitivity. Instead, we show that mitochondrial readiness for apoptosis, known as mitochondrial priming, differs between hESCs and differentiated cells. Specifically, the balance between proapoptotic and antiapoptotic proteins is shifted closer to the apoptotic threshold in hESCs than in differentiated cells. Altering this balance in differentiated cells increases their sensitivity and results in cell death, suggesting that manipulation of mitochondrial priming could potentially alter the sensitivity of other stem cells, including cancer stem cells. C1 [Liu, Julia C.; Rivera, Ana G.; Mock, Caroline; Lahav, Galit] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Letai, Anthony] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Guan, Xiao; Agarwal, Vishesh; Lerou, Paul H.] Brigham & Womens Hosp, Dept Pediat Newborn Med, Boston, MA 02115 USA. [Guan, Xiao; Agarwal, Vishesh; Lerou, Paul H.] Brigham & Womens Hosp, Div Genet, Dept Med, Boston, MA 02115 USA. [Ryan, Jeremy A.; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Lerou, Paul H.] Boston Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. [Lerou, Paul H.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Lerou, PH (reprint author), Brigham & Womens Hosp, Dept Pediat Newborn Med, 75 Francis St, Boston, MA 02115 USA. EM plerou@partners.org; galit@hms.harvard.edu OI Mock, Charles/0000-0002-0564-568X FU Molecular Biophysics Training Grant [NIH/NIGMS T32008313]; National Science Foundation; Harvard College Program for Research in Science and Engineering; FAS Center for Systems Biology; Charles H. Hood Foundation; NIH/NICHD [HD061981] FX We thank R. Agami for the p53shRNA construct; G. Daley for the CHB8 cell line; D. Melton for the HUES9 cell line; Y. Xu for the HUES9 p53-/- cell line; A. Baccei, B. Gorman, and K. Karhohs for assistance with IF imaging and analysis; J. Moore and J. Stewart-Ornstein for assistance with flow cytometry and analysis; J. Reyes for assistance with illustration; and E. Batchelor and all members of our laboratory for comments and discussions. J. C. L. was supported by the Molecular Biophysics Training Grant (NIH/NIGMS T32008313) and the National Science Foundation Graduate Research Fellowship. A. G. R. was supported by the Harvard College Program for Research in Science and Engineering and the FAS Center for Systems Biology. P. H. L. was supported by the Charles H. Hood Foundation and NIH/NICHD HD061981. NR 33 TC 41 Z9 43 U1 2 U2 5 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 OCT 3 PY 2013 VL 13 IS 4 BP 483 EP 491 DI 10.1016/j.stem.2013.07.018 PG 9 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 287VT UT WOS:000329571100016 PM 23954752 ER PT J AU Guo, GJ Luc, S Marco, E Lin, TW Peng, C Kerenyi, MA Beyaz, S Kim, W Xu, J Das, PP Neff, T Zou, KY Yuan, GC Orkin, SH AF Guo, Guoji Luc, Sidinh Marco, Eugenio Lin, Ta-Wei Peng, Cong Kerenyi, Marc A. Beyaz, Semir Kim, Woojin Xu, Jian Das, Partha Pratim Neff, Tobias Zou, Keyong Yuan, Guo-Cheng Orkin, Stuart H. TI Mapping Cellular Hierarchy by Single-Cell Analysis of the Cell Surface Repertoire SO CELL STEM CELL LA English DT Article ID HEMATOPOIETIC STEM-CELLS; GENE-EXPRESSION ANALYSIS; ACUTE MYELOID-LEUKEMIA; MOUSE BONE-MARROW; MESSENGER-RNA-SEQ; TRANSCRIPTION FACTOR; PROGENITOR CELLS; IDENTIFICATION; GATA-1; LINEAGES AB Stem cell differentiation pathways are most often studied at the population level, whereas critical decisions are executed at the level of single cells. We have established a highly multiplexed, quantitative PCR assay to profile in an unbiased manner a panel of all commonly used cell surface markers (280 genes) from individual cells. With this method, we analyzed over 1,500 single cells throughout the mouse hematopoietic system and illustrate its utility for revealing important biological insights. The comprehensive single cell data set permits mapping of the mouse hematopoietic stem cell differentiation hierarchy by computational lineage progression analysis. Further profiling of 180 intracellular regulators enabled construction of a genetic network to assign the earliest differentiation event during hematopoietic lineage specification. Analysis of acute myeloid leukemia elicited by MLL-AF9 uncovered a distinct cellular hierarchy containing two independent self-renewing lineages with different clonal activities. The strategy has broad applicability in other cellular systems. C1 [Guo, Guoji; Luc, Sidinh; Peng, Cong; Kerenyi, Marc A.; Beyaz, Semir; Kim, Woojin; Xu, Jian; Das, Partha Pratim; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Guo, Guoji; Luc, Sidinh; Peng, Cong; Kerenyi, Marc A.; Beyaz, Semir; Kim, Woojin; Xu, Jian; Das, Partha Pratim; Orkin, Stuart H.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Marco, Eugenio; Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Lin, Ta-Wei] Childrens Hosp, Mol Genet Core Facil, Boston, MA 02115 USA. [Neff, Tobias] Univ Colorado, Pediat Hematol Oncol BMT, Aurora, CO 80045 USA. [Zou, Keyong] Boston Open Labs, Cambridge, MA 02138 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu OI Neff, Tobias/0000-0002-0188-8393; Beyaz, Semir/0000-0003-4730-4012 FU National Institutes of Health; Harvard Stem Cell Institute FX We thank H. Skaletsky from Whitehead Institute for extensive help on the multiplexed primer design; Y. Fujiwara, E. Baena, O. Yilmaz, M. Nguyen, X. Han, V. Bragt, D. Linn, and J. Buchman for help with different parts of the sample preparations; and H. Huang, Z. Li, D. Scadden, H. Xie, and H. Hock for insightful discussions on the project. This work was supported by funding from the National Institutes of Health and the Harvard Stem Cell Institute (S. H. O). S. H. O. is an investigator of the Howard Hughes Medical Institute. NR 41 TC 86 Z9 87 U1 0 U2 19 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 OCT 3 PY 2013 VL 13 IS 4 BP 492 EP 505 DI 10.1016/j.stem.2013.07.017 PG 14 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 287VT UT WOS:000329571100017 PM 24035353 ER PT J AU Lassus, J Gayat, E Mueller, C Peacock, WF Spinar, J Harjola, VP van Kimmenade, R Pathak, A Mueller, T diSomma, S Metra, M Pascual-Figal, D Laribi, S Logeart, D Nouira, S Sato, N Potocki, M Parenica, J Collet, C Cohen-Solal, A Januzzi, JL Mebazaa, A AF Lassus, Johan Gayat, Etienne Mueller, Christian Peacock, W. Frank Spinar, Jindrich Harjola, Veli-Pekka van Kimmenade, Roland Pathak, Atul Mueller, Thomas diSomma, Salvatore Metra, Marco Pascual-Figal, Domingo Laribi, Said Logeart, Damien Nouira, Semir Sato, Naoki Potocki, Michael Parenica, Jiri Collet, Corinne Cohen-Solal, Alain Januzzi, James L., Jr. Mebazaa, Alexandre CA GREAT-Network TI Incremental value of biomarkers to clinical variables for mortality prediction in acutely decompensated heart failure: The Multinational Observational Cohort on Acute Heart Failure (MOCA) study SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE ADHF; Mortality; Risk prediction; Biomarkers; Reclassification ID IN-HOSPITAL MORTALITY; NATRIURETIC PEPTIDE; RISK STRATIFICATION; RENAL-FUNCTION; ROC CURVE; NT-PROBNP; DIAGNOSIS; RECLASSIFICATION; GUIDELINES; PROGNOSIS AB Aim: This study aims to evaluate the incremental value of plasma biomarkers to traditional clinical variables for risk stratification of 30-day and one-year mortality in acutely decompensated heart failure (ADHF). Methods and results: Through an international collaborative network, individual patient data on 5306 patients hospitalized for ADHF were collected. The all-cause mortality rate was 11.7% at 30 days and 32.9% at one year. The clinical prediction model (age, gender, blood pressure on admission, estimated glomerular filtration rate <60mL/min/1.73 m(2), sodium and hemoglobin levels, and heart rate) had a c-statistic of 0.74 for 30-day mortality and 0.73 for one-year mortality. Several biomarkers measured at presentation improved risk stratification when added to the clinical model. At 30 days, the net reclassification improvement (NRI) was 28.7% for mid-regional adrenomedullin (MR-proADM; p<0.001) and 25.5% for soluble (s) ST2 (p<.001). At one year, sST2 (NRI 10.3%), MR-proADM (NRI 9.1%), amino-terminal pro-B-type natriuretic peptide (NT-proBNP; NRI 9.1%), mid-regional proatrial natriuretic peptide (MR-proANP; NRI 7.4%), B-type natriuretic peptide (NRI 5.5%) and C-reactive protein (CRP; NRI 5.3%) reclassified patients with ADHF (p<0.05 for all). CRP also markedly improved risk stratification of patients with ADHF as a dual biomarker combination with MR-proADM (NRI 36.8% [p<0.001] for death at 30 days) or with sST2 (NRI 20.3%; [p<0.001] for one-year mortality). Conclusion: In this study, biomarkers provided incremental value for risk stratification of ADHF patients. Biomarkers such as sST2, MR-proADM, natriuretic peptides and CRP, reflecting different pathophysiologic pathways, add prognostic value to clinical risk factors for predicting both short-term and one-year mortality in ADHF. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Lassus, Johan; Harjola, Veli-Pekka] Univ Helsinki, Cent Hosp, Div Emergency Care, FIN-00014 Helsinki, Finland. [Lassus, Johan; Harjola, Veli-Pekka] Univ Helsinki, Cent Hosp, Dept Med, FIN-00014 Helsinki, Finland. [Lassus, Johan; Laribi, Said; Logeart, Damien; Collet, Corinne; Cohen-Solal, Alain; Mebazaa, Alexandre] Lariboisiere Univ Hosp, INSERM UMR 942, Paris, France. [Gayat, Etienne; Mebazaa, Alexandre] Lariboisiere Univ Hosp, AP HP, Dept Anesthesiol & Crit Care Med, Mobile Care Unit, Paris, France. [Gayat, Etienne] St Louis Univ Hosp, INSERM UMR 717, Paris, France. [Mueller, Christian; Potocki, Michael] Univ Basel Hosp, Dept Internal Med, CH-4031 Basel, Switzerland. [Peacock, W. Frank] Baylor Coll Med, Houston, TX 77030 USA. [Spinar, Jindrich; Parenica, Jiri] Univ Hosp Brno, Dept Internal Med & Cardiol, Brno, Czech Republic. [Spinar, Jindrich; Parenica, Jiri] Masaryk Univ, Fac Med, Brno, Czech Republic. [van Kimmenade, Roland] Univ Med Ctr Utrecht, Dept Cardiol, Utrecht, Netherlands. [Pathak, Atul] Toulouse Univ Hosp, Dept Cardiol, Toulouse, France. [Mueller, Thomas] Konventhosp Barmherzige Brueder, Dept Lab Med, Linz, Austria. [diSomma, Salvatore] Univ Roma La Sapienza, St Andrea Hosp, Emergency Dept, I-00185 Rome, Italy. [Metra, Marco] Univ Brescia, Dept Expt & Appl Med, Brescia, Italy. [Pascual-Figal, Domingo] Virgen Arrixaca Hosp, Serv Cardiol, Murcia, Spain. [Pascual-Figal, Domingo] Univ Murcia, Dept Med, Murcia, Spain. [Pascual-Figal, Domingo] Univ Murcia, Fac Med, Murcia, Spain. [Laribi, Said] Lariboisiere Univ Hosp, AP HP, Dept Emergency Med, Paris, France. [Logeart, Damien; Cohen-Solal, Alain] Lariboisiere Univ Hosp, AP HP, Dept Cardiol, Paris, France. [Nouira, Semir] Fattouma Bourguiba Univ Hosp, Emergency Dept, Monastir, Tunisia. [Nouira, Semir] Fattouma Bourguiba Univ Hosp, Res Unit UR06SP21, Monastir, Tunisia. [Sato, Naoki] Nippon Med Sch, Musashi Kosugi Hosp, Tokyo 113, Japan. [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Mebazaa, A (reprint author), Hop Lariboisiere, Dept Anesthesie Reanimat, 2 Rue Ambroise Pare, F-75475 Paris 10, France. EM Alexandre.Mebazaaa@lrb.aphp.fr RI Laribi, Said/D-5229-2014; Harjola, Veli-Pekka/G-9229-2015; Kimmenade, R.R.J./L-4432-2015; Laribi, said/S-3693-2016; OI Metra, Marco/0000-0001-6691-8568; Nouira, Semir/0000-0002-0137-5491; Samuel, Jane-Lise/0000-0002-7346-2404; Pascual Figal, Domingo A./0000-0002-4993-9540 FU Roche Diagnostics; Siemens Diagnostics; Critical Diagnostics; Thermo-Fisher Diagnostics; Abbott; Alere; Baxter; Brahms; Novartis; Medicine's Company; Lily FX JL speaker's honoraria from Abbott, consultant fees from Roche Diagnostics; JLJ grants from Roche Diagnostics, Siemens Diagnostics, Critical Diagnostics, Thermo-Fisher Diagnostics, consultant fees from Roche Diagnostics, Critical Diagnostics; V-PH consultant fees from Roche Diagnostics; WFP research grants from Abbott, Alere, Baxter, Brahms, Novartis, The Medicine's Company; consultant fees from Abbott, Alere, Lily, The Medicine's Company, speaker's honoraria from Abbott, Alere; ownership interest in Comprehensive Research Associates LLC, Vital Sensors, Emergencies in Medicine LLC, DP-F grants from Roche Diagnostics; CM research support and speaker's honoraria from BRAHMS, Alere, Abbott, and Critical Diagnostics; TM speaker's honoraria Abbott Diagnostics, B. R. A. H. M. S AG, and Roche Diagnostics, SdS consultant fees for Alere and Thermo-Fisher Diagnostics; AM speaker's honoraria from Alere, BRAHMS, Edwards, Orion, Bayer. NR 31 TC 56 Z9 58 U1 0 U2 19 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD OCT 3 PY 2013 VL 168 IS 3 BP 2186 EP 2194 DI 10.1016/j.ijcard.2013.01.228 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 241RF UT WOS:000326184400077 PM 23538053 ER PT J AU Ezekowitz, JA Bakal, JA Westerhout, CM Giugliano, RP White, H Keltai, M Prabhakaran, D Tricoci, P de Werf, FV Califf, RM Newby, LK Armstrong, PW AF Ezekowitz, Justin A. Bakal, Jeffrey A. Westerhout, Cynthia M. Giugliano, Robert P. White, Harvey Keltai, Matyas Prabhakaran, Dorairaj Tricoci, Pierluigi de Werf, Frans Van Califf, Robert M. Newby, L. Kristin Armstrong, Paul W. TI The relationship between meteorological conditions and index acute coronary events in a global clinical trial SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE Acute coronary syndromes; Climate; Temperature ID ACUTE MYOCARDIAL-INFARCTION; DAILY WEATHER CONDITIONS; TEMPERATURE; MORTALITY; ISCHEMIA; REGISTRY; PROJECT; DEATH; HEAT; RISK AB Background: Considerable uncertainty exists concerning the interaction between climate and human health. We explored this issue by evaluating the relationship between meteorological events and acute coronary syndrome (ACS) events. Methods: 9406 patients in 29 countries at 440 Early versus Delayed, Provisional Eptifibatide in Acute Coronary Syndromes (EARLY ACS) clinical trial sites were linked to a weather station by location. Temperature, barometric pressure, precipitation, wind speed and combined temperature and relative humidity were normalized by location for the 37 days prior to the index ACS event that precipitated study enrollment. A meteorological event was defined as a change in any weather metric that was expected to occur in less than 10% of the exposure intervals: four separate 48-hour intervals within the seven days prior to an ACS event (T1, day of event and-1 day; T2, -2 to -3 days; T3, -4 to -5 days; and T4, -6 to -7 days). Results are reported as ratio of observed to expected events for the meteorological parameter. Results: There were 10% more drops in temperature observed in T4 (95% CI: 3-17%), and more increases in temperature observed during T1 (4%; 95% CI-2-9%). An excess number of wind speed increases (9%; 95% CI 2-16%) and relative humidity increases (6%; 95% CI 0.1-14%) occurred during T4. Additionally, female patients in this cohort presented less often than male patients following drops in average temperature. Conclusions: Using a new method for integrating meteorological data into a clinical trial dataset, we identified associations between changes in weather conditions and the likelihood of an ACS event. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Ezekowitz, Justin A.] Univ Alberta, Dept Med, Div Cardiol, Edmonton, AB, Canada. [Ezekowitz, Justin A.] Mazankowski Alberta Heart Inst, Edmonton, AB, Canada. [Bakal, Jeffrey A.; Westerhout, Cynthia M.; Armstrong, Paul W.] Univ Alberta, Edmonton, AB, Canada. [Giugliano, Robert P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [White, Harvey] Auckland City Hosp, Auckland, New Zealand. [Keltai, Matyas] Semmelweis Univ, Hungarian Inst Cardiol, H-1085 Budapest, Hungary. [Prabhakaran, Dorairaj] Ctr Chron Dis Control, New Delhi, India. [Tricoci, Pierluigi; Califf, Robert M.; Newby, L. Kristin] Duke Clin Res Inst, Durham, NC USA. RP Ezekowitz, JA (reprint author), 2C2 Walter Mackenzie Hlth Sci Cntr,8440-112 St, Edmonton, AB T6G 2B7, Canada. EM jae2@ualberta.ca RI Ezekowitz, Justin/C-4579-2013; OI Ezekowitz, Justin/0000-0002-2724-4086; Van de Werf, Frans/0000-0001-9479-7767; Prabhakaran, Dorairaj/0000-0002-3172-834X FU Schering Plough FX Funding: Schering Plough provided the funding for the EARLY ACS trial, however they had no role associated with this current study. NR 21 TC 3 Z9 3 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD OCT 3 PY 2013 VL 168 IS 3 BP 2315 EP 2321 DI 10.1016/j.ijcard.2013.01.061 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 241RF UT WOS:000326184400096 PM 23416014 ER PT J AU Castro, ML Barbosa, MM Barbosa, JAA de Almeida, FR Esteves, WAD Tan, TC Nunes, MCP AF Castro, Marildes L. Barbosa, Marcia M. Barbosa, Jose Augusto A. de Almeida, Fernanda Rodrigues Esteves, William Antonio de Magalhaes Tan, Timothy C. Nunes, Maria Carmo P. TI Value of right ventricular strain in predicting functional capacity in patients with mitral stenosis SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Mitral stenosis; Right ventricular function; Right ventricular strain; Functional capacity ID HEART-DISEASE; ECHOCARDIOGRAPHY C1 [Castro, Marildes L.; de Almeida, Fernanda Rodrigues; Esteves, William Antonio de Magalhaes; Nunes, Maria Carmo P.] Univ Fed Minas Gerais, Sch Med, Postgrad Program Infect Dis & Trop Med, Belo Horizonte, MG, Brazil. [Barbosa, Marcia M.; Barbosa, Jose Augusto A.] Hosp Socor, Ecoctr, Belo Horizonte, MG, Brazil. [Tan, Timothy C.; Nunes, Maria Carmo P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA. RP Nunes, MCP (reprint author), Univ Fed Minas Gerais, Dept Clin Med, Av Prof Alfredo Balena 190, BR-30130100 Belo Horizonte, MG, Brazil. EM mcarmo@waymail.com.br NR 16 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD OCT 3 PY 2013 VL 168 IS 3 BP 2927 EP 2930 DI 10.1016/j.ijcard.2013.03.181 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 241RF UT WOS:000326184400210 PM 23651817 ER PT J AU Chen, C Xu, JM Huang, F AF Chen, Chan Xu, Junmei Huang, Feng TI Recent players in the field of acute myocardial infarction biomarkers: Circulating cell-free DNA or microRNAs? SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Acute myocardial infarction; Biomarkers; Cell-free DNA; Circulating microRNAs ID PROGNOSTIC MARKER; CHEST-PAIN C1 [Chen, Chan; Xu, Junmei] Cent S Univ, Dept Anesthesiol, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China. [Chen, Chan; Xu, Junmei] Cent S Univ, Anesthesiol Res Inst, Changsha 410011, Hunan, Peoples R China. [Chen, Chan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Huang, Feng] Cent S Univ, Dept Cardiol, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China. RP Xu, JM (reprint author), Cent S Univ, Dept Anesthesiol, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China. EM doctorjmxu@gmail.com NR 16 TC 4 Z9 4 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD OCT 3 PY 2013 VL 168 IS 3 BP 2956 EP 2957 DI 10.1016/j.ijcard.2013.03.118 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 241RF UT WOS:000326184400224 PM 23602868 ER PT J AU Abtahian, F Yonetsu, T Vergallo, R Jia, HB Kato, K Tian, JW Hu, SN McNulty, I Jang, IK AF Abtahian, Farhad Yonetsu, Taishi Vergallo, Rocco Jia, Haibo Kato, Koji Tian, Jinwei Hu, Sining McNulty, Iris Jang, Ik-Kyung TI Ticagrelor immediately prior to stenting is associated with smaller residual thrombus in patients with acute coronary syndrome SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Percutaneous coronary intervention; Platelet; P2Y12; Optical coherence tomography ID MYOCARDIAL-INFARCTION; INTERVENTION; CLOPIDOGREL; IMPACT; TRIAL C1 [Abtahian, Farhad; Yonetsu, Taishi; Vergallo, Rocco; Jia, Haibo; Kato, Koji; Tian, Jinwei; Hu, Sining; McNulty, Iris; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Jia, Haibo; Tian, Jinwei; Hu, Sining] Harbin Med Univ, Dept Cardiol, Affiliated Hosp 2, Key Lab Myocardial Ischemia,Chinese Minist Educ, Harbin, Peoples R China. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM ijang@partners.org NR 10 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD OCT 3 PY 2013 VL 168 IS 3 BP 3099 EP 3101 DI 10.1016/j.ijcard.2013.04.076 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 241RF UT WOS:000326184400299 PM 23642594 ER PT J AU Poultney, CS Goldberg, AP Drapeau, E Kou, Y Harony-Nicolas, H Kajiwara, Y De Rubeis, S Durand, S Stevens, C Rehnstrom, K Palotie, A Daly, MJ Ma'ayan, A Fromer, M Buxbaum, JD AF Poultney, Christopher S. Goldberg, Arthur P. Drapeau, Elodie Kou, Yan Harony-Nicolas, Hala Kajiwara, Yuji De Rubeis, Silvia Durand, Simon Stevens, Christine Rehnstroem, Karola Palotie, Aarno Daly, Mark J. Ma'ayan, Avi Fromer, Menachem Buxbaum, Joseph D. TI Identification of Small Exonic CNV from Whole-Exome Sequence Data and Application to Autism Spectrum Disorder SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID COPY-NUMBER VARIATION; DE-NOVO MUTATIONS; HUMAN GENOME; GENE; TOOL; REVEALS; DISCOVERY; NETWORK; 17P13.1; MAP AB Copy number variation (CNV) is an important determinant of human diversity and plays important roles in susceptibility to disease. Most studies of CNV carried out to date have made use of chromosome microarray and have had a lower size limit for detection of about 30 kilobases (kb). With the emergence of whole-exome sequencing studies, we asked whether such data could be used to reliably call rare exonic CNV in the size range of 1-30 kilobases (kb), making use of the eXome Hidden Markov Model (XHMM) program. By using both transmission information and validation by molecular methods, we confirmed that small CNV encompassing as few as three exons can be reliably called from whole-exome data. We applied this approach to an autism case-control sample (n = 811, mean per-target read depth = 161) and observed a significant increase in the burden of rare (MAF <= 1%) 1-30 kb CNV, 1-30 kb deletions, and 1-10 kb deletions in ASD. CNV in the 1-30 kb range frequently hit just a single gene, and we were therefore able to carry out enrichment and pathway analyses, where we observed enrichment for disruption of genes in cytoskeletal and autophagy pathways in ASD. In summary, our results showed that XHMM provided an effective means to assess small exonic CNV from whole-exome data, indicated that rare 1-30 kb exonic deletions could contribute to risk in up to 7% of individuals with ASD, and implicated a candidate pathway in developmental delay syndromes. C1 [Poultney, Christopher S.; Goldberg, Arthur P.; Drapeau, Elodie; Kou, Yan; Harony-Nicolas, Hala; Kajiwara, Yuji; De Rubeis, Silvia; Durand, Simon; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [Poultney, Christopher S.; Goldberg, Arthur P.; Drapeau, Elodie; Harony-Nicolas, Hala; Kajiwara, Yuji; De Rubeis, Silvia; Durand, Simon; Fromer, Menachem; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Goldberg, Arthur P.; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA. [Kou, Yan; Ma'ayan, Avi] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [Kou, Yan; Ma'ayan, Avi] Icahn Sch Med Mt Sinai, Syst Biol Ctr New York, New York, NY 10029 USA. [Stevens, Christine; Palotie, Aarno; Daly, Mark J.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Rehnstroem, Karola; Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00290 Helsinki, Finland. [Rehnstroem, Karola] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Fromer, Menachem; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Neurosci, Dept Genet & Genom Sci, New York, NY 10029 USA. [Fromer, Menachem; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. RP Buxbaum, JD (reprint author), Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. EM joseph.buxbaum@mssm.edu RI De Rubeis, Silvia/E-9852-2013; OI De Rubeis, Silvia/0000-0001-9383-6883; Buxbaum, Joseph/0000-0001-8898-8313 FU National Institute of Mental Health, National Institutes of Health [MH089025, MH097849, MH100233]; Seaver Foundation FX This work was supported by the National Institute of Mental Health, National Institutes of Health (grants MH089025, MH097849, and MH100233 to J.D.B.) and the Seaver Foundation. C.S.P. is a Seaver Fellow and A.P.G. is a Seaver Fellow. NR 47 TC 54 Z9 56 U1 0 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT 3 PY 2013 VL 93 IS 4 BP 607 EP 619 DI 10.1016/j.ajhg.2013.09.001 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 243GT UT WOS:000326305600003 PM 24094742 ER PT J AU Austin-Tse, C Halbritter, J Zariwala, MA Gilberti, RM Gee, HY Hellman, N Pathak, N Liu, Y Panizzi, JR Patel-King, RS Tritschler, D Bower, R O'Toole, E Porath, JD Hurd, TW Chaki, M Diaz, KA Kohl, S Lovric, S Hwang, DY Braun, DA Schueler, M Airik, R Otto, EA Leigh, MW Noone, PG Carson, JL Davis, SD Pittman, JE Ferkol, TW Atkinson, JJ Olivier, KN Sagel, SD Dell, SD Rosenfeld, M Milla, CE Loges, NT Omran, H Porter, ME King, SM Knowles, MR Drummond, IA Hildebrandt, F AF Austin-Tse, Christina Halbritter, Jan Zariwala, Maimoona A. Gilberti, Renee M. Gee, Heon Yung Hellman, Nathan Pathak, Narendra Liu, Yan Panizzi, Jennifer R. Patel-King, Ramila S. Tritschler, Douglas Bower, Raqual O'Toole, Eileen Porath, Jonathan D. Hurd, Toby W. Chaki, Moumita Diaz, Katrina A. Kohl, Stefan Lovric, Svjetlana Hwang, Daw-Yang Braun, Daniela A. Schueler, Markus Airik, Rannar Otto, Edgar A. Leigh, Margaret W. Noone, Peadar G. Carson, Johnny L. Davis, Stephanie D. Pittman, Jessica E. Ferkol, Thomas W. Atkinson, Jeffry J. Olivier, Kenneth N. Sagel, Scott D. Dell, Sharon D. Rosenfeld, Margaret Milla, Carlos E. Loges, Niki T. Omran, Heymut Porter, Mary E. King, Stephen M. Knowles, Michael R. Drummond, Iain A. Hildebrandt, Friedhelm TI Zebrafish Ciliopathy Screen Plus Human Mutational Analysis Identifies C21orf59 and CCDC65 Defects as Causing Primary Ciliary Dyskinesia SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DYNEIN REGULATORY COMPLEX; OUTER ARM DYNEIN; CHLAMYDOMONAS-REINHARDTII; PROTEOMIC ANALYSIS; MOTILE CILIA; SCHMIDTEA-MEDITERRANEA; KARTAGENER-SYNDROME; FLAGELLAR MOTILITY; SEQUENCE-ANALYSIS; DISEASE GENES AB Primary ciliary dyskinesia (PCD) is caused when defects of motile cilia lead to chronic airway infections, male infertility, and situs abnormalities. Multiple causative PCD mutations account for only 65% of cases, suggesting that many genes essential for cilia function remain to be discovered. By using zebrafish morpholino knockdown of PCD candidate genes as an in vivo screening platform, we identified c21orf59, ccdc65, and c15orf26 as critical for cilia motility. c21orf59 and c15orf26 knockdown in zebrafish and planaria blocked outer dynein arm assembly, and ccdc65 knockdown altered cilia beat pattern. Biochemical analysis in Chlamydomonas revealed that the C21orf59 ortholog FBB18 is a flagellar matrix protein that accumulates specifically when cilia motility is impaired. The Chlamydomonas ida6 mutant identifies CCDC65/FAP250 as an essential component of the nexin-dynein regulatory complex. Analysis of 295 individuals with PCD identified recessive truncating mutations of C21orf59 in four families and CCDC65 in two families. Similar to findings in zebrafish and planaria, mutations in C21orf59 caused loss of both outer and inner dynein arm components. Our results characterize two genes associated with PCD-causing mutations and elucidate two distinct mechanisms critical for motile cilia function: dynein arm assembly for C21orf59 and assembly of the nexin-dynein regulatory complex for CCDC65. C1 [Austin-Tse, Christina; Hellman, Nathan; Pathak, Narendra; Liu, Yan; Panizzi, Jennifer R.; Drummond, Iain A.] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA 02129 USA. [Austin-Tse, Christina; Drummond, Iain A.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Nephrol,Dept Genet, Boston, MA 02115 USA. [Halbritter, Jan; Gee, Heon Yung; Porath, Jonathan D.; Kohl, Stefan; Lovric, Svjetlana; Hwang, Daw-Yang; Braun, Daniela A.; Schueler, Markus; Airik, Rannar; Hildebrandt, Friedhelm] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Zariwala, Maimoona A.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. [Gilberti, Renee M.; Patel-King, Ramila S.; King, Stephen M.] Univ Connecticut, Ctr Hlth, Dept Mol Microbial & Struct Biol, Farmington, CT 06030 USA. [Tritschler, Douglas; Bower, Raqual; Porter, Mary E.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. [O'Toole, Eileen] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder Lab Electron Microscopy Cells 3D, Boulder, CO 80309 USA. [Hurd, Toby W.; Chaki, Moumita; Diaz, Katrina A.; Otto, Edgar A.] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. [Leigh, Margaret W.; Noone, Peadar G.; Carson, Johnny L.; Davis, Stephanie D.; Pittman, Jessica E.] Univ N Carolina, Sch Med, Dept Pediat, Chapel Hill, NC 27599 USA. [Ferkol, Thomas W.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Atkinson, Jeffry J.] Washington Univ, Sch Med, Div Pulm & Crit Care, St Louis, MO 63110 USA. [Olivier, Kenneth N.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Sagel, Scott D.] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO 80045 USA. [Dell, Sharon D.] Univ Toronto, Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada. [Rosenfeld, Margaret] Childrens Hosp, Seattle, WA 98105 USA. [Rosenfeld, Margaret] Univ Washington, Seattle, WA 98105 USA. [Milla, Carlos E.] Stanford Univ, Dept Pediat, Stanford, CA 94304 USA. [Loges, Niki T.; Omran, Heymut] Univ Childrens Hosp Muenster, Dept Gen Pediat, D-48149 Munster, Germany. [Knowles, Michael R.] Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC 27599 USA. [Hildebrandt, Friedhelm] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Drummond, IA (reprint author), Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA 02129 USA. EM idrummond@partners.org; friedhelm.hildebrandt@childrens.harvard.edu OI Austin-Tse, Christina/0000-0001-6492-6716; Otto, Edgar/0000-0002-2387-9973 FU National Institutes of Health; Howard Hughes Medical Institute; Deutsche Forschungsgemeinschaft; IZKF Muenster; European Community FX We are grateful to all PCD subjects and family members for their participation and thank the US PCD Foundation and to the investigators and the coordinators of the "Genetic Disorders of Mucociliary Clearance Consortium." We are also grateful to the funding agencies that supported this work; these include the National Institutes of Health, the Howard Hughes Medical Institute, the Deutsche Forschungsgemeinschaft, the IZKF Muenster, and the European Community's Seventh Framework Programme. Detailed acknowledgements can be found in the Supplemental Data. NR 71 TC 47 Z9 54 U1 0 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT 3 PY 2013 VL 93 IS 4 BP 672 EP 686 DI 10.1016/j.ajhg.2013.08.015 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 243GT UT WOS:000326305600009 PM 24094744 ER PT J AU Richardson, PG Schlossman, RL Alsina, M Weber, DM Coutre, SE Gasparetto, C Mukhopadhyay, S Ondovik, MS Khan, M Paley, CS Lonial, S AF Richardson, Paul G. Schlossman, Robert L. Alsina, Melissa Weber, Donna M. Coutre, Steven E. Gasparetto, Cristina Mukhopadhyay, Sutapa Ondovik, Michael S. Khan, Mahmudul Paley, Carole S. Lonial, Sagar TI PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma SO BLOOD LA English DT Article ID LENALIDOMIDE PLUS DEXAMETHASONE; DIAGNOSED MULTIPLE-MYELOMA; WORKING GROUP; THERAPY; MULTICENTER; CRITERIA; PHASE-2; LBH589 AB Panobinostat is an oral pan-deacetylase inhibitor that synergizes with bortezomib to inhibit both the aggresome and proteasome pathways in preclinical studies. PANORAMA 2 is a phase 2 trial of panobinostat in combination with bortezomib and dexamethasone to treat patients with relapsed and bortezomib-refractory multiple myeloma (with >= 2 prior lines of therapy, including an immunomodulatory drug, and patients who had progressed on or within 60 days of the last bortezomib-based therapy). Fifty-five heavily pretreated patients were enrolled (median, 4 prior regimens, including a median of 2 prior bortezomib-containing regimens). The overall response rate was 34.5% (1 near-complete response and 18 partial responses). An additional 10 patients achieved minimal response, for a clinical benefit rate of 52.7%. Median exposure and progression-free survival were 4.6 and 5.4 months, respectively. In patients who achieved a response, median time to response was 1.4 months, and median duration of response was 6.0 months. Common grade 3/4 adverse events, regardless of study drug relationship, included thrombocytopenia (63.6%), fatigue (20.0%), and diarrhea (20.0%). Only 1 patient had grade 3 peripheral neuropathy. Panobinostat, when combined with bortezomib and dexamethasone, can recapture responses in heavily pretreated, bortezomib-refractory multiple myeloma patients. C1 [Richardson, Paul G.; Schlossman, Robert L.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02215 USA. [Alsina, Melissa] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Weber, Donna M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Coutre, Steven E.] Stanford Canc Ctr, Palo Alto, CA USA. [Coutre, Steven E.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Gasparetto, Cristina] Duke Univ, Med Ctr, Durham, NC USA. [Mukhopadhyay, Sutapa; Ondovik, Michael S.; Khan, Mahmudul; Paley, Carole S.] Novartis Pharmaceut, E Hanover, NJ USA. [Lonial, Sagar] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. RP Richardson, PG (reprint author), Harvard Univ, Dana Farber Canc Inst, 450 Brookline Ave,Mailstop Dana 1B02, Boston, MA 02215 USA. EM paul_richardson@dfci.harvard.edu FU Novartis Pharmaceuticals Corporation; Novartis FX This study was supported in part by research funding for clinical studies and medical editorial assistance from Novartis Pharmaceuticals Corporation and Novartis research funding (D.M.W.). NR 25 TC 105 Z9 106 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD OCT 3 PY 2013 VL 122 IS 14 BP 2331 EP 2337 DI 10.1182/blood-2013-01-481325 PG 7 WC Hematology SC Hematology GA 240ER UT WOS:000326078200016 PM 23950178 ER PT J AU Vlachos, A Farrar, JE Atsidaftos, E Muir, E Narla, A Markello, TC Singh, SA Landowski, M Gazda, HT Blanc, L Liu, JM Ellis, SR Arceci, RJ Ebert, BL Bodine, DM Lipton, JM AF Vlachos, Adrianna Farrar, Jason E. Atsidaftos, Eva Muir, Ellen Narla, Anupama Markello, Thomas C. Singh, Sharon A. Landowski, Michael Gazda, Hanna T. Blanc, Lionel Liu, Johnson M. Ellis, Steven R. Arceci, Robert J. Ebert, Benjamin L. Bodine, David M. Lipton, Jeffrey M. TI Diminutive somatic deletions in the 5q region lead to a phenotype atypical of classical 5q-syndrome SO BLOOD LA English DT Article ID DIAMOND-BLACKFAN ANEMIA; PROTEIN GENE DELETIONS; IDENTIFICATION; LENALIDOMIDE AB Classical 5q- syndrome is an acquired macrocytic anemia of the elderly. Similar to Diamond Blackfan anemia (DBA), an inherited red cell aplasia, the bone marrow is characterized by a paucity of erythroid precursors. RPS14 deletions in combination with other deletions in the region have been implicated as causative of the 5q- syndrome phenotype. We asked whether smaller, less easily detectable deletions could account for a syndrome with a modified phenotype. We employed single-nucleotide polymorphism array genotyping to identify small deletions in patients diagnosed with DBA and other anemias lacking molecular diagnoses. Diminutive mosaic deletions involving RPS14 were identified in a 5-year-old patient with nonclassical DBA and in a 17-year-old patient with myelodysplastic syndrome. Patients with nonclassical DBA and other hypoproliferative anemias may have somatically acquired 5q deletions with RPS14 haploinsufficiency not identified by fluorescence in situ hybridization or cytogenetic testing, thus refining the spectrum of disorders with 5q- deletions. C1 [Vlachos, Adrianna; Singh, Sharon A.; Blanc, Lionel; Liu, Johnson M.; Lipton, Jeffrey M.] Steven & Alexandra Cohen Childrens Med Ctr New Yo, New Hyde Pk, NY 11040 USA. [Vlachos, Adrianna; Atsidaftos, Eva; Muir, Ellen; Singh, Sharon A.; Blanc, Lionel; Liu, Johnson M.; Lipton, Jeffrey M.] Feinstein Inst Med Res, Manhasset, NY USA. [Farrar, Jason E.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Narla, Anupama; Ebert, Benjamin L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Narla, Anupama; Gazda, Hanna T.; Ebert, Benjamin L.] Harvard Univ, Sch Med, Boston, MA USA. [Narla, Anupama; Ebert, Benjamin L.] Brigham & Womens Hosp, Dept Hematol, Boston, MA 02115 USA. [Markello, Thomas C.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Landowski, Michael; Gazda, Hanna T.] Childrens Hosp Boston, Div Genet, Manton Ctr Orphan Dis Res, Boston, MA USA. [Landowski, Michael; Gazda, Hanna T.] Childrens Hosp Boston, Program Genom, Manton Ctr Orphan Dis Res, Boston, MA USA. [Ellis, Steven R.] Univ Louisville, Louisville, KY 40292 USA. [Arceci, Robert J.] Johns Hopkins Univ, Baltimore, MD USA. [Bodine, David M.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Vlachos, A (reprint author), Steven & Alexandra Cohen Childrens Med Ctr New Yo, 269-01 76th Ave, New Hyde Pk, NY 11040 USA. EM avlachos@nshs.edu OI Farrar, Jason/0000-0003-2148-5839; Blanc, Lionel/0000-0002-0185-6260 FU Diamond Blackfan Anemia Foundation; Pediatric Cancer Foundation; Arkansas Biosciences Institute; Feinstein Institute for Medical Research General Clinical Research Center [M01 RR018535]; Centers for Disease Control-sponsored Diamond Blackfan Anemia Surveillance and Awareness Program; National Institutes of Health [R01-HL079571, R01-HL107558, R109-MOHLKE, K02-HL111156, K08-HL092224]; National Human Genome Research Institute Intramural funds; St. Baldrick's Foundation Scholar Career Development Award; St. Baldrick's Consortium on Pediatric Myelodysplastic Syndrome FX This work was supported in part by grants from the Diamond Blackfan Anemia Foundation (H. T. G., D. M. B., A. V., E. M.), the Pediatric Cancer Foundation (J.M. Lipton), the Arkansas Biosciences Institute (J.E.F.), The Feinstein Institute for Medical Research General Clinical Research Center (M01 RR018535; A. V., J.M. Lipton), the Centers for Disease Control-sponsored Diamond Blackfan Anemia Surveillance and Awareness Program (A. V., E. M.), and the National Institutes of Health (R01-HL079571 [A. V., E. A., J.M. Lipton], R01-HL107558 [H. T. G.], R109-MOHLKE [A. V., E. A., J.M. Lipton], K02-HL111156 [H. T. G.], K08-HL092224 [J.E.F.], and National Human Genome Research Institute Intramural funds [D. M. B.]), St. Baldrick's Foundation Scholar Career Development Award (S. A. S.), and St. Baldrick's Consortium on Pediatric Myelodysplastic Syndrome (J.M. Liu). NR 16 TC 6 Z9 6 U1 0 U2 2 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 OCT 3 PY 2013 VL 122 IS 14 BP 2487 EP 2490 DI 10.1182/blood-2013-06-509935 PG 4 WC Hematology SC Hematology GA 240ER UT WOS:000326078200032 PM 23943650 ER PT J AU Levy, O Zhao, WA Mortensen, LJ LeBlanc, S Tsang, K Fu, MY Phillips, JA Sagar, V Anandakumaran, P Ngai, J Cui, CH Eimon, P Angel, M Lin, CP Yanik, MF Karp, JM AF Levy, Oren Zhao, Weian Mortensen, Luke J. LeBlanc, Sarah Tsang, Kyle Fu, Moyu Phillips, Joseph A. Sagar, Vinay Anandakumaran, Priya Ngai, Jessica Cui, Cheryl H. Eimon, Peter Angel, Matthew Lin, Charles P. Yanik, Mehmet Fatih Karp, Jeffrey M. TI mRNA-engineered mesenchymal stem cells for targeted delivery of interleukin-10 to sites of inflammation SO BLOOD LA English DT Article ID VERSUS-HOST-DISEASE; BONE-MARROW; STROMAL CELLS; IN-VIVO; MYOCARDIAL-INFARCTION; THERAPEUTIC-EFFICACY; ADHESION MOLECULE-1; MICE; ENGRAFTMENT; TRANSPLANTATION AB Mesenchymal stem cells (MSCs) are promising candidates for cell-based therapy to treat several diseases and are compelling to consider as vehicles for delivery of biological agents. However, MSCs appear to act through a seemingly limited "hit-and-run" mode to quickly exert their therapeutic impact, mediated by several mechanisms, including a potent immunomodulatory secretome. Furthermore, MSC immunomodulatory properties are highly variable and the secretome composition following infusion is uncertain. To determine whether a transiently controlled antiinflammatory MSC secretome could be achieved at target sites of inflammation, we harnessed mRNA transfection to generate MSCs that simultaneously express functional rolling machinery (P-selectin glycoprotein ligand-1 [PSGL-1] and Sialyl-Lewis(x) [SLeX]) to rapidly target inflamed tissues and that express the potent immunosuppressive cytokine interleukin-10 (IL-10), which is not inherently produced by MSCs. Indeed, triple-transfectedPSGL-1/SLeX/IL-10 MSCs transiently increased levels of IL-10 in the inflamed ear and showed a superior antiinflammatory effect in vivo, significantly reducing local inflammation following systemic administration. This was dependent on rapid localization of MSCs to the inflamed site. Overall, this study demonstrates that despite the rapid clearance of MSCs in vivo, engineered MSCs can be harnessed via a "hit-and-run" action for the targeted delivery of potent immunomodulatory factors to treat distant sites of inflammation. C1 [Levy, Oren; Zhao, Weian; LeBlanc, Sarah; Tsang, Kyle; Fu, Moyu; Sagar, Vinay; Anandakumaran, Priya; Ngai, Jessica; Cui, Cheryl H.; Karp, Jeffrey M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Biomed Engn,Dept Med,Ctr Regenerat Therapeut, Cambridge, MA 02139 USA. [Levy, Oren; Zhao, Weian; LeBlanc, Sarah; Tsang, Kyle; Fu, Moyu; Sagar, Vinay; Anandakumaran, Priya; Ngai, Jessica; Cui, Cheryl H.; Karp, Jeffrey M.] Harvard Stem Cell Inst, Cambridge, MA USA. [Levy, Oren; Zhao, Weian; LeBlanc, Sarah; Tsang, Kyle; Fu, Moyu; Sagar, Vinay; Anandakumaran, Priya; Ngai, Jessica; Cui, Cheryl H.; Karp, Jeffrey M.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA USA. [Mortensen, Luke J.; Phillips, Joseph A.; Lin, Charles P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02139 USA. [Mortensen, Luke J.; Phillips, Joseph A.; Lin, Charles P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Cambridge, MA 02139 USA. [Eimon, Peter; Angel, Matthew; Yanik, Mehmet Fatih] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Yanik, Mehmet Fatih] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. RP Karp, JM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02139 USA. EM yanik@mit.edu; jeffkarp.bwh@gmail.com FU NIH, Heart, Lung and Blood Institute [HL095722]; American Heart Association [0970178N]; Prostate Cancer Foundation FX This work was supported by NIH, Heart, Lung and Blood Institute grant HL095722 to J.M.K, and by the American Heart Association grant 0970178N to J.M.K. This work was also supported by a Prostate Cancer Foundation Challenge Award to J.M.K. NR 51 TC 49 Z9 50 U1 1 U2 22 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 OCT 3 PY 2013 VL 122 IS 14 BP E23 EP E32 DI 10.1182/blood-2013-04-495119 PG 10 WC Hematology SC Hematology GA 240ER UT WOS:000326078200002 PM 23980067 ER PT J AU Scirica, BM Bhatt, DL Braunwald, E Steg, PG Davidson, J Hirshberg, B Ohman, P Frederich, R Wiviott, SD Hoffman, EB Cavender, MA Udell, JA Desai, NR Mosenzon, O McGuire, DK Ray, KK Leiter, LA Raz, I Braunwald, E Bhatt, DL Scirica, BM Udell, JA Cavender, MA Desai, N Abrahamsen, T Grossman, M Morin, S Im, K Hoffman, E Gabovitch, D Pricken, A Mosenzon, O Buskila, A Ohman, P Hirshberg, B Stahre, C Price, D Billing-Clason, S Sabel, K Monyak, J Sjostrand, M Wei, C Lu, J Miller, E Raichlen, J Fitt, S Frederich, R Iqbal, N Donovan, M Davidson, JA Steg, PG Aguilar-Salinas, C Alvarsson, M Amerena, J Ardissino, D Averkov, O Avogaro, A Barnett, A Bretzel, R Chiang, CE Codoceo, V Corbalan, R Dalby, A Darius, H Deerochanawong, C Dellborg, M Eliaschewitz, F Garcia-Castillo, A Gomis, R Henry, P Hoekstra, J Jermendy, G Kastelein, J Keech, A Kiss, R Krempf, M Laakso, M Leiter, L Leitersdorf, E Lewis, B Litwak, L Lopez-Sendon, J Ma, R McGuire, D Medina, F Moses, R Nicolau, JC Opolski, G Ophuis, TO Paolasso, E Ray, KK Ruda, M Kumar, KMP Shestakova, M Sheu, WHH Smahelova, A Bhupathiraju, BSR Spinar, J Sritata, P Strojeck, K Villena-Chavez, JE Jia, WP Huo, Y Wiviott, SD Lowe, C Awtry, E Berger, C Desai, AS Gelfand, E Leeman, D Link, M Ruberg, F Vita, J Rost, N Silverman, S Greenberger, NJ Lerch, MM Gersh, B Nesto, R Del Prato, S Tuomilehto, J Kelsey, S Alvarisqueta, A Cuadrado, J Rista, L Hermida, S Baccaro, C Luquez, C Lagrutta, M Maffei, L Bartolacci, I Montana, O Cutuli, H Berli, M Lorenzatti, A Frechtel, G La Greca, R Fretes, O Diaz, M Papini, NR Farias, E Issa, C Elbert, A Lehman, R Arya, M Singh, B Colquhoun, D Jayasinghe, R de Looze, F Blombery, P Ward, G Szto, G Abhayaratna, W Borges, J Russo, L Felicio, J Santos, F Guimaraes, F Castro, ML Rossi, P Armaganijan, D Leaes, P Bandeira, F Franken, M Rassi, N Rea, R Zanella, M Amodeo, C Cesar, L Betti, R Chacra, A Schmid, H Bell, A Syan, G Zadra, R Conter, H Dumas, R Borts, D Dattani, I Poirier, P Cha, J Dzongowski, P Labonte, R St Pierre, B Gaudet, D Kouz, S Lamy, A Tishler, S Chehayeb, R Bedard, J Hramiak, I Teitelbaum, I Fortin, C Woo, V Conway, J Mehta, P Robinson, S Sussex, B Chiasson, J Muirhead, N Bose, S Ouellet, A Yale, J Bhargava, R Lau, D Tobe, S Perron, P Sigalas, J Bilodeau, L Tytus, R Achyuthan, G Pearce, M Steele, A Bailey, G Ma, P St-Maurice, F Rupka, D Houlden, R Bailey, A Rewa, G Sohal, P Ting, R Prieto, J Rodriguez, M Godoy, G Larenas, G Pincetti, C Cobos, L Saavedra, V Varleta, P Lucero, F Kuzmanic, O Acevedo, M Aguirre, M Florenzano, F Ma, J Bao, Y Jiang, M Xu, W Shi, Y Zheng, M Li, Y Dong, Y Zhao, W Sun, M Lei, M Wang, J Pistek, Z Rihacek, I Kucera, D Brada, M Naplava, R 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CA Savor-Timi Steering Comm Investig TI Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIALS; INCRETIN-BASED THERAPIES; BLOOD-GLUCOSE CONTROL; VASCULAR OUTCOMES; CLINICAL-TRIAL; HEART-FAILURE; ALL-CAUSE; METAANALYSIS; EVENTS; DEATH AB BackgroundThe cardiovascular safety and efficacy of many current antihyperglycemic agents, including saxagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, are unclear. MethodsWe randomly assigned 16,492 patients with type 2 diabetes who had a history of, or were at risk for, cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years. Physicians were permitted to adjust other medications, including antihyperglycemic agents. The primary end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. ResultsA primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group (7.3% and 7.2%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio with saxagliptin, 1.00; 95% confidence interval [CI], 0.89 to 1.12; P=0.99 for superiority; P<0.001 for noninferiority); the results were similar in the on-treatment analysis (hazard ratio, 1.03; 95% CI, 0.91 to 1.17). The major secondary end point of a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or heart failure occurred in 1059 patients in the saxagliptin group and in 1034 patients in the placebo group (12.8% and 12.4%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio, 1.02; 95% CI, 0.94 to 1.11; P=0.66). More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure (3.5% vs. 2.8%; hazard ratio, 1.27; 95% CI, 1.07 to 1.51; P=0.007). Rates of adjudicated cases of acute and chronic pancreatitis were similar in the two groups (acute pancreatitis, 0.3% in the saxagliptin group and 0.2% in the placebo group; chronic pancreatitis, <0.1% and 0.1% in the two groups, respectively). ConclusionsDPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events, though the rate of hospitalization for heart failure was increased. Although saxagliptin improves glycemic control, other approaches are necessary to reduce cardiovascular risk in patients with diabetes. C1 [Bhatt, Deepak L.] VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA. 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[Sosale, A.] DIACON Hosp & Res Ctr, Bangalore, Karnataka, India. [Shamanna, P.] Bangalore Clinisearch, Bangalore, Karnataka, India. [Srikanta, S.] Jnana Sanjeevini Med Ctr, Bangalore, Karnataka, India. [Shah, S.] Diabet Act Ctr, Bombay, Maharashtra, India. [Srinivas, A.] Vikram Hosp Private Ltd, Mysore, Karnataka, India. [Kumar, K. M. Prasanna] Bangalore Diabet Hosp Bengaluru, Bangalore, Karnataka, India. [Banker, D.] Bankers Heart Inst, Vadodara, India. [Shah, P.] Gujarat Endocrine Ctr, Ahmadabad, Gujarat, India. [Sharda, A.] Endocrinol & Diabet Ctr, Bangalore, Karnataka, India. [Makkar, B.] Diabet & Obes Ctr, New Delhi, India. [Desai, N.] Namana Med Ctr, Bangalore, Karnataka, India. [Rais, N.] Chowpatty Med Ctr, Bombay, Maharashtra, India. [Mardikar, H.] Spandan Heart Inst, Nagpur, Maharashtra, India. [Mishra, A.] Fortis Flt Lt Rajan Dhall Hosp, New Delhi, India. [Bhupati, S.] CARE Hosp, Hyderabad, Andhra Pradesh, India. [Menon, J.] Mar Augustine Golden Jubilee Hosp, Mookkannur, Kerala, India. [Sathe, S.] Dr Shireesh Sathe Clin, Pune, Maharashtra, India. [Gupta, R.] Fortis Escorts Hosp, Jaipur, Rajasthan, India. [Sharma, V.] NHIAI Heart Fdn, New Delhi, India. [Darawsha, M.] Diabet & Lipid Dept Linn MC, Haifa, Israel. [Herskovits, T.] Western Galillee Hosp Diabet Inst, Nahariyya, Israel. [Hamoud, S.] Rambam Med Ctr Internal Med Haifa, Haifa, Israel. [Nikolsky, E.] Rambam Hlth Care Campus Dept Cardiol, Haifa, Israel. [Raz, Itamar] Hadassah Ein Karem MC Diabet Unit, Jerusalem, Israel. [Adawi, F.] Ziv Med Ctr, Endocrinol Unit, Safed, Israel. [Zimlichman, R.] Tel Aviv Community Ctr, Tel Aviv, Israel. [Tsalihin, D.] Ben Yair Community Clin Beer Sheva, Beer Sheva, Israel. [Wainstein, J.] Wolfson Med Ctr, Diabet Unit, Holon, Israel. [Klainman, E.] Gefen Cardiac Hlth Ctr, Giv'atayim, Israel. [Mosseri, M.] Meir Med Ctr, Div Cardiol, Kefar Sava, Israel. [Yerushalmi, Y.] Clalit Tel Aviv Diabet Clin, Tel Aviv, Israel. [Karnieli, E.] Rambam Med Ctr, Inst Endocrinol, Haifa, Israel. [Knobler, H.] Kaplan Med Ctr Metabol Unit, Rehovot, Israel. [Zimlichman, R.] Wolfson Med Ctr Med & Hypertens, Holon, Israel. [Benchetrit, S.] Meir MC Blood Pressure & Nephrol, Kefar Sava, Israel. [Tsur, A.] Clalit Hlth Serv Diabet Clin, Jerusalem, Israel. [Yagil, Y.] Barzilai Med Ctr Nephrol, Ashqelon, Israel. [Lewis, Basil] Lady Davis Carmel Med Ctr, Haifa, Israel. [Atar, S.] Western Galilee Hosp Cardiol, Nahriya, Israel. [Beberashvili, I.] Assaf Harofeh Med Ctr Nephrol, Beer Yaagov, Israel. [Fuchs, S.] Beilinson Med Ctr, Dept Internal Med, Petah Tiqwa, Israel. [Stern, N.] Sourasky Med Ctr, Metabol Unit, Tel Aviv, Israel. [Pollak, A.] Hadassah Med Org, Inst Heart, Jerusalem, Israel. [Chajek-Shaul, T.] Hadassah Hosp Mt Scopus Internal Med, Jerusalem, Israel. [Rozenman, Y.] Wolfson Med Ctr Heart Inst, Holon, Israel. [Biton, A.] Clalit Clin Dimona, Dimona, Israel. [Ardissino, Diego] AOU, Parma, Italy. [Bramucci, E.] OP San Matteo, Pavia, Italy. [Fiscella, A.] AO Cannizzaro, Catania, Italy. [Grassia, V.] POS Maria delle Grazie, Pozzuoli, Italy. [Piatti, P.] Ist Ricovero & Cura Carattere Sci, Milan, Italy. [Piatti, P.] Univ Osped San Raffaele, Milan, Italy. [De Cosmo, S.] Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy. [Di Lorenzo, L.] Osped San Rocco, Sessa Aurunca, Italy. [Merlini, P.] Osped Niguarda Ca Granda, Milan, Italy. [Mannucci, E.] AOU Careggi, Florence, Italy. [Frontoni, S.] Osped Fatebenefratelli, Rome, Italy. [Trevisan, R.] Osped Riuniti Bergamo, I-24100 Bergamo, Italy. [Zenari, L.] Osped Sacro Cuore Don Calabria, Negrar, Italy. [Avogaro, Angelo] AO Padova, Padua, Italy. [Lambiase, C.] Osped Amico Gaetano Fucito, Mercato San Severino, Italy. [Salvioni, A.] Osped Cardiol Monzino, Milan, Italy. [Silvestri, O.] AO Cardarelli, Naples, Italy. [Ambrosio, G.] Osped Santa Maria Terni, Terni, Italy. [Di Bartolo, P.] AUSL Ravenna, Ravenna, Italy. [Fattore, L.] PO San Giuseppe, S Maria Capua Vetere, Italy. [Presbitero, P.] Ist Clin Humanitas, Rozzano, Italy. [Calabrese, M.] AUSL 4, Prato, Italy. [Evola, R.] Osped San Vincenzo USL 5, Taormina, Italy. [Alcocer Gamba, M.] Inst Corazon Queretaro, Queretaro, Mexico. [de los Rios Ibarra, M. Odin] Ctr Desarrollo Med & Asistencia Med Especializada, Culiacan, Mexico. [Cardona Munoz, E.] ICLE SC, Guadalajara, Jalisco, Mexico. [Reyes Sanchez, D.] Cardioprevent SC, Durango, Mexico. [Hernandez Herrera, C.] Ctr Desarrollo Med & Asistencia Med Especializada, Monclova, Mexico. [Perez Rios, J.] Oaxaca Site Management Org, Oaxaca De Juarez, Mexico. [Bayram Llamas, E.] Fdn Cardiovasc Aguascalientes AC, Aguascalientes, Mexico. [Llamas Esperon, G.] Hosp Cardiol Aguascalientes, Aguascalientes, Mexico. [Garcia Cantu, E.] Cardiolink Clin Trials SC, Monterrey, Mexico. Hosp Gen Durango, Durango, Mexico. [Gonzalez Gonzalez, J.] Hosp Univ Dr Jose Eleuterio Gonzalez, Monterrey, Mexico. [Rivera Martinez, G.] Hosp Gen Tijuana, Tijuana, Mexico. [Padilla Padilla, F.] Consultorios Tarascos, Guadalajara, Jalisco, Mexico. [Melendez Mier, G.] Ctr Invest Med Mexico MENTRIALS SA de CV, Mexico City, DF, Mexico. [Herrera Marmolejo, D.] Torre Med Prov, Guadalajara, Jalisco, Mexico. [Garza Ruiz, J.] Internal Med Clin Trials, Monterrey, Mexico. [Caracas Portilla, N.] Hosp Angeles Lindavista, Mexico City, DF, Mexico. [Lopez Rosas, E.] Ctr Especialidades Med Estado Veracruz CEMEV, Xalapa, Veracruz, Mexico. [Aguilar-Salinas, Carlos] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, Mexico. [Mendez Machado, G.] Med Este, Xalapa, Veracruz, Mexico. [Chevaile Ramos, J.] Hosp Cent Dr Ignacio Morones Prieto, San Luis Potosi, Mexico. [Rodriguez Briones, I.] Cardioarritmias & Invest SC, San Luis Potosi, Mexico. [van Hessen, M. W. J.] Groene Hart Ziekenhuis Locatie Bleuland, Gouda, Netherlands. [Strikwerda, S.] Amphia Ziekenhuis Locatie Molengracht, Breda, Netherlands. Bethesda Ziekenhuis, Hoogeveen, Netherlands. [Kooy, A.] Bethesda Diabet Res Ctr, Hoogeveen, Netherlands. [Ronner, E.] Reinier de Graaf Gasthuis, Delft, Netherlands. [Nierop, P. R.] St Franciscus Gasthuis, Rotterdam, Netherlands. [Remmen, J. J.] Canisius Wilhelmina Ziekenhuis, Nijmegen, Netherlands. [Groenemeijer, B. E.] Gelre Ziekenhuizen Loc Lukas Ziekenhuis, Apeldoorn, Netherlands. [Hamer, B. J. B.] Meander Med Ctr, Amersfoort, Netherlands. [Basart, D. C. G.] Vasc Onderzoeksctr Hoorn BV, Hoorn, Netherlands. [van Lennep, H. W. O. Roeters] Admiraal Ruyterziekenhuis, Goes, Netherlands. [Nieuwdorp, M.] AMC, Amsterdam, Netherlands. [van Dijk, M. P. M.] Julius Ctr UMCU, Utrecht, Netherlands. [Kentgens, S.] Andromed Eindhoven, Eindhoven, Netherlands. [van Kempen, W. W.] Andromed Rotterdam, Rotterdam, Netherlands. [Hoogendijk, J.] Andromed Oost, Velp, Netherlands. [Spiering, W.] UMCU, Utrecht, Netherlands. [Voors-Pette, C.] Andromed Noord, Groningen, Netherlands. [Kose, V.] Andromed Breda, Breda, Netherlands. [de Waard, D. E. P.] Antonius Ziekenhuis, Sneek, Netherlands. [Gonkel, F.] Saxenburgh Grp Ropcke Zweers Ziekenhuis, Hardenberg, Netherlands. [Kaasjager, H. A. H.] Rijnstate Ziekenhuis, Arnhem, Netherlands. [Lingan, G. M. Rojas] Andromed Zoetermeer, Eindhoven, Netherlands. [Agous, I.] Andromed Leiden, Leiderdorp, Netherlands. [Kruik, H. J.] Ziekenhuis Grp Twente Lokatie Almelo, Almelo, Netherlands. [Imholz, B. P. M.] Tweesteden Ziekenhuis, Waalwijk, Netherlands. [Pieterse, M.] Stichting Cardiol Amsterdam, Amsterdam, Netherlands. [Manrique, H.] Ctr Expertos Diabet Obesidad & Nutr, Lima, Peru. [Medina, Felix] Clin Med Cayetano Heredia, Lima, Peru. [Villena, J.] Hosp Nacl Cayetano Heredia, Lima, Peru. [Leon, L.; Heredia, J.] Clin Anglo Am, Lima, Peru. [Kundert, K.] Ctr Invest Ricardo Palma, Lima, Peru. [Minchola, J.] Clin San Gabriel, Lima, Peru. [Pinto, M.] Clin Oftalmolaser, Lima, Peru. [Rodriguez, A.] Hosp Nacl Alberto Sabogal Sologuren, Callao, Peru. [Guerreros, C.] Clin Int, Lima, Peru. [Berrospi, P.] Clin El Golf, Lima, Peru. [Zubiate, C.] METABOLICARE, Lima, Peru. [Allemant, A.] Hosp Nacl Hipolito Unanue, Lima, Peru. [Arbanil, H.] Hosp Nacl Dos de Mayo, Lima, Peru. [Ponciano, W.] Clin San Borja, Lima, Peru. [Calderon, J.] Clin Novocardio, Lima, Peru. [Lisson, R.] Hosp Nacl Edgardo Rebagliati Martins, Lima, Peru. [Segura, L.] Inst Med Miraflores, Lima, Peru. [Sidorowicz-Bialynicka, A.] Synexus SCM, Wroclaw, Poland. [Sciborski, R.] Zespol Opieki Zdrowotnej Olawie SPZOZ, Olawa, Poland. [Fares, I.] NZOZ Medicus, Naklo Nad Notecia, Poland. [Mader, P.] NZOZ Praktyka Dentystyczno Internistyczna, Kamieniec Zabkowicki, Poland. [Skierkowska, J.] NZOZ JUDYTA, Skierniewice, Poland. [Stasinska, T.] NZOZ Regionalna Poradnia Diabetol, Wroclaw, Poland. [Pomiecko, W.] Samodzielny Niepubl ZOZ Mazur Med, Mragowo, Poland. [Skorski, M.] SPZOZ Lecznej Szpital Powiatowy, Leczna, Poland. [Krzyzagorska, E.] Praktyka Lekarska Ewa Krzyzagorska, Poznan, Poland. [Polaszewska-Muszynska, M.] Bydgoskie Ctr Diabetol & Endokrynol SPZOZ, Bydgoszcz, Poland. [Sowinski, D.] Wroclawiu SP ZOZ, Wojewodzki Zespol Specjalistycznej Opieki Zdrowot, Wroclaw, Poland. [Strojek, K.] Wojewodzka Przychodnia Chorych Cukrzyce, Zabrze, Poland. [Rosinska-Migda, J.] NZOZ Mig Med, Wabrzezno, Poland. [Romanczuk, P.] NZOZ Gdanska Poradnia Cukrzycowa, Gdansk, Poland. [Golebiowski, G.] Szpital Specjalisty Sw Wojciecha Adalberta SP ZOZ, Gdansk, Poland. [Kubica, J.] NZOZ MEDICUS Jacek Kubica, Bydgoszcz, Poland. [Mazurek, T.] I Katedra & Klin Kardiol Akad Med, Warsaw, Poland. [Wojnowski, L.] Lecznice Citomed, Torun, Poland. [Pasternak, D.] NZOZ Ctr Zdrowia & Profilaktyki Dabie, Krakow, Poland. [Stachlewski, P.] NZOZ Eskulap, Koluszki, Poland. [Trzepla, E.] Ctr Med Warszawskiego Uniwersytetu Med, Warsaw, Poland. [Bogdanowicz, G.] PS ZOZ Wojewodzkie Ctr Med, Opole, Poland. [Uzunow, A.] Przychodnia Med Rodzinnej Nowy Fordon, Bydgoszcz, Poland. [Potakowska, I.] Zespol Poradni Zdrowie NZOZ, Sieradz, Poland. [Miszczyszyn, Z.] Prywatny Specjalisty Gabinet Lekarski, Przemysl, Poland. [Waszyrowski, T.] Wojewodzka Stacja Ratownictwa Med Lodzi SPZOZ, Lodz, Poland. [Smolenskaya, O.] Hosp 14 Ural State Med Acad Ekat, Ekaterinburg, Russia. [Lukyanov, Y.] State Med Univ Na Pavlov, St Petersburg, Russia. [Vorokhobina, N.] Chair Endocrinol Med Postgrad Acad, St Petersburg, Russia. [Khalimov, Y.] Endocrinol NII Med Postgrad Acad, St Petersburg, Russia. [Orlikova, O.] Res Inst Cardiol Saratov, Saratov, Russia. [Rebrov, A.] SGMU Na Razumovsky Saratov, Saratov, Russia. [Kukharchuk, V.] Atherosclerosis Problems Dept Cardiocomplex, Moscow, Russia. [Boldueva, S.] Cardiol Clin Mechnikov Med Acad, St Petersburg, Russia. [Arkhipov, M.] MO Novaya Ural State Med Acad Ekat, Ekaterinburg, Russia. [Zhelninova, T.] Out Patient Dep Almazov Fed Ctr, St Petersburg, Russia. [Pavlysh, E.] Out Patient Dept 25, St Petersburg, Russia. [Antsiferov, M.] Moscow Endocrinol Dispensary, Moscow, Russia. [Panov, A.] Cardiol Dep Almazov Fed Ctr, St Petersburg, Russia. [Pavlova, M.] MMA Na Sechenov IM, Moscow, Russia. [Shustov, S.] Mil Med Acad Na Kirov, St Petersburg, Russia. [Demchenko, E.] Rehabil Lab Almazov Fed Ctr, St Petersburg, Russia. [Galyavich, A.] KGMU Kazan, Kazan, Russia. [Malakhina, E.] Ctr New Med Technol Novosibirsk, Novosibirsk, Russia. [Semenova, O.] Alexandrovskaya City Hosp, St Petersburg, Russia. [Kobalava, Z.] City Clin Hosp 64, Moscow, Russia. [Shestakova, Marina] Inst Diabet Sci Ctr Endocri, Moscow, Russia. [Kotova, S.] Chair Endocrinol Mechnikov Med Acad, St Petersburg, Russia. [Gavrisheva, I.] OOO AVA Peter, St Petersburg, Russia. [Oschepkova, E.] Arterial Hypertens Dept Cardiocomplex, Moscow, Russia. [Karpov, Y.] Angiol Dept Cardiocomplex, Moscow, Russia. [Sidorenko, B.] Cent Clin Hosp, Moscow, Russia. [Kislyak, O.] City Clin Hosp 79, Moscow, Russia. [Ametov, A.] Chair Endocrinol RMAPO, Moscow, Russia. [Dreval, A.] Moscow Res Clin Inst Na Vladimirsky, Moscow, Russia. [Grineva, E.] Endocrinol Inst Almazov Fed Ctr, St Petersburg, Russia. [Mkrtumyan, A.] MGMSU, Moscow, Russia. [Tyurina, T.] Leningrad Reg Cardiol Dispensary, St Petersburg, Russia. [Sazonova, O.] Novosibirsk State Med Univ, Novosibirsk, Russia. [Ranjith, N.] Dr Nash Ranjith Res Ctr, Durban, South Africa. [Burgess, L.] TREAD Res Tygerberg Hosp, Parow, South Africa. [Nortje, H.] Unit B1 N1 City Mews, Cape Town, South Africa. [Distiller, L.] Ctr Diabet & Endocrinol, Johannesburg, South Africa. [Mitha, I.] Worthwhile Clin Trials Lakeview Hosp, Benoni, South Africa. [Moore, R.] 14 Medigate Med Ctr, Umhlanga Rocks, South Africa. [Conradie, M.] Tygerberg Hosp, Endocrine Unit, Parow, South Africa. [Horak, A.] Vincent Pallotti Hosp, Pinelands, South Africa. [Pillay, S.] Dr SR Pillay Practice, Ottawa, Verulam, South Africa. [Wellmann, H.] Helderberg Diabat & Med Ctr, Cape Town, South Africa. [Berg, E.] Dr EC Van den Berg Practice Zuid Afrikaans Hosp, Pretoria, South Africa. [Pillai, P.] Drs Chetty & Pillai Med Ctr, Phoenix, South Africa. [Padayachee, T.] Aliwal Shoal Med Ctr, Umkomaas, South Africa. [Corbett, C.] Panorama Mediclin, Cape Town, South Africa. [Makan, H.] Seva Sadan, Lenasia, South Africa. [Wing, J.] Charlotte Maxeke Johannesburg Acad Hosp, Johannesburg, South Africa. [Vawda, Z.] Dr ZFA Vawdas Practice, Durban, South Africa. [Ebrahim, I.] Unitas Hosp, Centurion, South Africa. [Dalby, A.] Milpark Hosp, Johannesburg, South Africa. [Mitha, E.] Newgate Ctr, Johannesburg, South Africa. [Bhorat, A.] Soweto Clin Trial Ctr, Soweto, South Africa. [Cruz Fernandez, J.] Hosp Univ Virgen Macarena, Seville, Spain. [Munoz, C.] Hosp Gen Jerez de la Frontera, Jerez De La Frontera Cad, Spain. [Bruguera Cortada, J.] Hosp del Mar, Barcelona, Spain. [Castro Conde, A.] Hosp Cantoblanco La Paz, Madrid, Spain. [Calvo, C.] Hosp Univ Santiago, Santiago De Compostela, Spain. [Gil Extremera, B.] Hosp Clin San Cecilio, Granada, Spain. [Delgado, E.] Hosp Univ Cent Asturias, Oviedo, Spain. [Masmiquel, L.] Hosp Son Llatzer, Palma de Mallorca, Spain. [Garcia Puig, J.] Hosp Univ La Paz, Madrid, Spain. [de Teresa Parreno, L.] Clin Mediterranea Neurociencias, Alicante, Spain. [Mauricio, D.] Hosp Arnau Vilanova, Lerida, Spain. [Redon, J.] Hosp Clin Univ Valencia, Valencia, Spain. [Brito, M.] Hosp Univ Puerta Hierro Majadahonda, Majadahonda Madrid, Spain. [Lopez, C.] Ctr Salud El Cristo, Oviedo, Spain. [Segura de la Morera, J.] Hosp Univ Doce de Octubre, Madrid, Spain. [Linderfalk, C.] Redeby Eksjo, Eksjo, Sweden. [Larnefeldt, H.] Rattvikshalsan, Rattvik, Sweden. [Olsson, A.] Sthlm Heart Ctr, Stockholm, Sweden. [Lonneborg, L.; Albin, J.] Sorakers Vardcent, Soraker, Sweden. [Ekelund, M.] Hbg Lasarett, Helsingborg, Sweden. [Samad, B.] Danderyd, Stockholm, Sweden. [Borgencrantz, B.] Capio Lakargrp AB Orebro, Orebro, Sweden. [Nilsson, J.] Skanes Univ Sjukhus Malmo, Malmo, Sweden. [Berglund, O.] Alidhem Umea, Umea, Sweden. [Svensson, M.] SU SS Gbg, Gothenburg, Sweden. [Mooe, T.] Ostersunds Sjukhus, Ostersund, Sweden. [Alvarsson, Michael] KS Solna, Stockholm, Sweden. [Curiac, D.] Me3and Gbg, Stockholm, Sweden. [Angesjo, E.] Bramhults VC, Bramhult, Sweden. [Lannemyr, O.] Lanssjukhuset Ryhov, Jonkoping, Sweden. [Dellborg, Mikael] SU Ostra Gbg, Gothenburg, Sweden. [Chiang, C.] Taipei Vet Gen Hosp, Taipei, Taiwan. [Sheu, W.] Taichung Vet Gen Hosp, Taichung, Taiwan. [Chen, J.] Chang Gung Med Fdn Kaohsiung Branch, Kaohsiung, Taiwan. [Tien, K.] Chi Mei Med Ctr, Tainan, Taiwan. [Ueng, K.] Chung Shan Med Univ Hosp, Taichung 40201, Taiwan. [Lai, W.] Kaohsiung Med Univ Hosp, Kaohsiung, Taiwan. [Yin, W.] Cheng Hsin Gen Hosp, Taipei, Taiwan. [Hung, Y.] Tri Serv Gen Hosp, Taipei, Taiwan. [Shyu, K.] Shin Kong Wu Ho Su Mem Hosp, Taipei, Taiwan. [Hou, J.] Mackay Mem Hosp, Taipei, Taiwan. [Lam, H.] Kaohsiung Vet Gen Hosp, Kaohsiung, Taiwan. [Laothavorn, P.; Benjasuratwong, Y.] Phramongkutklao Hosp, Bangkok, Thailand. [Sritata, Piyamitr] Ramathibodi Hosp, Bangkok, Thailand. [Kuanprasert, S.] MaharajNakornChiangMai Hosp, Chiangmai, Thailand. [Deerochanawong, Chaicharn] Rajavithi Hosp, Bangkok, Thailand. [Khovidhunkit, W.] King Chulalongkorn Mem Hosp, Bangkok, Thailand. [Chotinaiwattarakul, C.; Nitiyanant, W.] Siriraj Hosp, Bangkok, Thailand. [Mamanasiri, S.] Ratchaburi Hosp, Ratchaburi, Thailand. [Suraamornkul, S.] Vajira Hosp, Bangkok, Thailand. [Pratipanawatr, T.] Srinagarind Hosp, Khon Kaen, Thailand. [Pieters, R.] Estuary View Med Ctr, Whitstable, England. [Strang, C.] Mortimer Surg, Mortimer Reading, England. [Bodalia, B.] Gables Med Ctr, Coventry, W Midlands, England. [Middleton, A.] Fowey River Practice, Fowey, England. [Hall, T.] Knowle House Surg, Plymouth, Devon, England. [Chapman, G.] Sunbury Hlth Ctr, Sunbury On Thames, England. [Calvert, J.] Waterloo Med Ctr, Blackpool, England. [Reed, R.] Westongrove Res Ctr Aston Clinton Surg, Aston Clinton Aylesbur, England. [Tam, D.] Circle Practice, Kenton, England. [Butcher, G.] Ecclesfield Grp Practice, Sheffield, S Yorkshire, England. [Jones, N.] St Chads Surg, Bath, Avon, England. [Takhar, A.] Wansford & Kings Cliffe Practice, Wansford Peterborough, England. [Turner, W.] Burbage Surg, Burbage Leicester, England. [McNally, D.] Ormeau Hlth Ctr, Belfast, Antrim, North Ireland. [Corey, O.] Ave Surg, Warminister, England. [Chapman, J.] Widcombe Surg, Bath, Avon, England. [Mohr, S.] Porch Surg, Bath, Avon, England. [Edwards, S.] Elm Tree Surg, Swindon, Wilts, England. [Ocampo, A.] Future Care Solut LLC, Miami, FL USA. [Kandath, D.] Saratoga Clin Res LLC, Saratoga Springs, NY USA. [Aude, Y.] Valley Heart Consultants, Mcallen, TX USA. [Ervin, W.] InterMed PA, Portland, ME USA. [Savin, V.] Kansas City VA Med Ctr, Kansas City, MO USA. [Anderson, R.] VA Nebraska Western Iowa Healthcare Syst, Omaha, NE USA. [Littlefield, R.] Palmetto Res Ctr LLC, Spartanburg, SC USA. [Oberoi, M.] Cent Jersey Med Res Ctr, Elizabeth, NJ USA. [Yazdani, S.] Virginia Cardiovasc Associates, Manassas, VA USA. [Mangoo-Karim, R.] Gamma Clin Res Inst, Mission, TX USA. [Walder, J.] Black Hills Cardiovasc Res, Rapid City, SD USA. [Gogia, H.] Cardiol Consultants Orange Cty Med Grp Inc, Anaheim, CA USA. [Chandrashekhar, Y.] VA Med Ctr, Minneapolis, MN USA. [Boccalandro, F.] Permian Res Fdn, Odessa, TX USA. [Rogers, W., Jr.] Univ Alabama Birmingham, Med Ctr, Birmingham, AL 35294 USA. [Bilazarian, S.] Pentucket Med Associates, Haverhill, MA USA. [Zieve, F.] McGuire VA Med Ctr, Richmond, VA USA. [Siage, Y.] Deaconess Clin Inc, Evansville, IN USA. [O'Connor, T.] Am Hlth Network Indiana LLC, Greenfield, IN USA. [Mudaliar, S.] VA San Diego Healthcare Syst, San Diego, CA USA. [Nikas, A.] Hlth Texas Res Inst, San Antonio, TX USA. [Giusti, R.] Clin Res Cent Florida, Winter Haven, FL USA. [Glover, R.] Heartland Res Associates LLC, Newton, KS USA. [Chilka, S.] Midland Clin Res Ctr, Midland, TX USA. [French, W.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst Harbor, Torrance, CA 90509 USA. [Roth, E.] Sterling Res Grp Ltd, Cincinnati, OH USA. [Singh, N.] Atlanta Heart Specialists LLC, Cumming, GA USA. [Christofferson, R.] North Ohio Res Ltd, Elyria, OH USA. [Stich, M.] Westside Ctr Clin Res, Jacksonville, FL USA. [Dagogo-Jack, S.] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA. [Allison, J., III] Three Rivers Med Associates, Columbia, SC USA. [Zengotita, G. Arroyo] Jardines Loiza, Georgina Arroyo Zengotita Med Familia, Loiza, PR USA. [Ison, R.] Community Hlth Care Inc, Canal Fulton, OH USA. [Iteld, B.] Louisiana Heart Ctr, Slidell, LA USA. [Sulistio, M.; Raskin, P.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Gonzalez, E.] Eastside Clin Res Associates Inc, Los Angeles, CA USA. [Gorman, T.] Great Lakes Med Res, Westfield, NY USA. [Hage-Korban, E.] Kore CV Res, Jackson, TN USA. [Reddy, R.] T&R Clin PA, Ft Worth, TX USA. [Byars, W.] Mt View Clin Res, Greer, SC USA. [Antonishen, M.] Northern Michigan Reg Hosp, Petoskey, MI USA. [Benjamin, S.] Universal Res Grp, Tacoma, WA USA. [First, B.] Ritchken & First MDs, San Diego, CA USA. [Rosado, J.] Florida Heart & Vasc Ctr, Leesburg, FL USA. [Bruschetta, H.] Humberto Rafael Bruschetta, Kingsville, TX USA. [Mehta, P.; Poling, T.] Heartland Res Associates LLC, Wichita, KS USA. [Rosendorff, C.] James J Peters VA Med Ctr, Bronx, NY USA. [Saba, F.] Profess Hlth Care Pinellas Inc, St Petersburg, FL USA. [Willis, J.] San Gabriel Clin Res, Georgetown, TX USA. [Adams, K.] Baptist Heart Specialists, Jacksonville, FL USA. [Vazquez, E. Camilo] Cent Res Clin Puerto Rico, Aguas Buenas, PR USA. [Ellison, H.] Rockdale Med Res Associates, Conyers, GA USA. [Kahn, B.] Overlea Personal Phys, Baltimore, MD USA. [Kereiakes, D.] Christ Hosp, Carl & Edyth Lindner Ctr Res & Educ, Cincinnati, OH 45219 USA. [Powell, S.] PMG Res Bristol, Bristol, TN USA. [Smith, K.] Burke Primary Care, Morganton, NC USA. [Varma, S.] Boice Willis Clin PA, Rocky Mount, NC USA. [Whittier, F.] Clin Res Ltd, Canton, OH USA. [Casanova, R.] South East Med Ctr, Oakland Pk, FL USA. [Isserman, S.] Clin Trials Am Inc, Hickory, NC USA. [Kaye, W.] Metab Res Inst Inc, W Palm Beach, FL USA. [McGuinn, W., II] North Ohio Res Ltd, Sandusky, OH USA. [Bartkowiak, A., Jr.] Blair Med Associates PA, Altoona, PA USA. [Dworkin, L.] Rhode Isl Hosp, Providence, RI USA. [Podlecki, D.] Longmont Med Res Network, Longmont, CO USA. [Popovtzer, M.] Southern Arizona VA Healthcare Syst, Tucson, AZ USA. [Aronoff, S.] Res Inst Dallas PA, Dallas, TX USA. [Ballantyne, C.] Baylor Coll Med, Houston, TX 77030 USA. [Mora, A., III] Southwest Clin, San Antonio, TX USA. [Pitts, T.] Diverse Clin Res Ctr Chicago LLC, Chicago, IL USA. [Reinhardt, S.] Cent Bucks Cardiol, Doylestown, PA USA. [Soucie, G.] Blackfoot Med Ctr, Blackfoot, ID USA. [Wainwright, W.] Baptist Heart Specialists, Jacksonville Beach, FL USA. [Henson, B.] Essentia Inst Rural Hlth, Duluth, MN USA. [Sklaver, N.] Med Specialists Associated, Dallas, TX USA. [Arakaki, R.] Univ Hawaii, Diabet & Endocrinol, Honolulu, HI 96822 USA. [Brown, J.] Internal Med Associates Grand Isl PC, Grand Isl, NE USA. [Chalavarya, G.] Florida Cardiol Grp, Hudson, FL USA. [Dixon, T.] Northport Vet Affairs Med Ctr, Northport, NY USA. [Kutner, M.] Suncoast Res Grp LLC, Miami, FL USA. [Perlman, R.] Associated Cardiovasc Consultants, Voorhess, NJ USA. [Raisinghani, A.] Univ Calif San Diego, Med Ctr, 225 Dickinson St, San Diego, CA 92103 USA. [Salacata, A.] Endeavor Med Res, Alpena, MI USA. [Awasty, V.] Harrison Community Res Ctr, Cadiz, OH USA. [Elinoff, V.] Reg Clin Res Inc, Endwell, NY USA. [George, W.] Cadillac Clin Res LLC, Cadillac, MI USA. [LaRochelle-Gryseels, A.] Sharon Reg Phys Serv, Hermitage, PA USA. [Mercado, A.] Stewart Med Grp, Alhambra, CA USA. [Miller, G.] Clin Res Works, Bristol, CT USA. [Qureshi, M.] Michigan Heart PC, Ypsilanti, MI USA. [Steljes, A.] Steljes Cardiol PC, Henderson, NV USA. [Wefald, F.] Clin Trials Am Inc, Smithfield, NC USA. [Wilson, J.] PMG Res Winston Salem, Winston Salem, NC USA. [Chinn, J.] VA Southern Nevada Hlth Care Syst, N Las Vegas, NV USA. [Chuang, Rita B.] Clin Res Advantage Inc, Henderson, NV USA. [Comulada-Rivera, A.] Inst Endocrinol Diabet & Metab, Bayamon, PR USA. [Hartman, I.] Discovery Clin Trials, Arlington, TX USA. [Narayan, P.] Clin Res Inst Northern Virginia, Burke, VA USA. [Pacheco, T.] North Ohio Res Ltd, Lorain, OH USA. [Weiss, R.] Cent Maine Med Ctr, Lewiston, ME USA. [Beavins, J.] Am Hlth Network Indiana LLC, Franklin, IN USA. [Creevy, J.] Intercoastal Med Grp, Sarasota, FL USA. [Hamroff, G.] NYU Hudson Valley Cardiol, Cortlandt Manor, NY USA. [Hodson, R.] Oregon Clin Gateway, Providence Heart Clin, Portland, OR USA. [Kosinski, E.] Connecticut Clin Res LLC, Bridgeport, CT USA. [Krichmar, P.] Res Phys Network Alliance, Pembroke Pines, FL USA. [Patel, R.] Lycoming Internal Med Inc, Jersey Shore, PA USA. [Schneider, R.] Holy Cross Med Grp, Coral Springs, FL USA. [Shapiro, J.] Philadelphia Hlth Associates Adult Med PC, Philadelphia, PA USA. [Sharp, D.] Clin Res Advantage Inc Internal Med Phys PC, Omaha, NE USA. [Speer, J.] Clin Res Advantage Colorado Springs Hlth Partners, Colorado Springs, CO USA. [Stegemoller, R.] Am Hlth Network Indiana LLC, Avon, IN USA. [Waxman, F.] GSA Med Res, Deerfield Beach, FL USA. [Chang, F. Young] Pasco Cardiol Ctr, Hudson, FL USA. [Braun, E.] Midtown Med Ctr, Tampa, FL USA. [Eder, F.] United Med Associates, Binghamton, NY USA. [Minor, S.] Austin Heart PLLC, San Marcos, TX USA. [Albert, M.] Acadia Clin Res LLC, Bangor, ME USA. [Diaczok, B.] St Joseph Mercy Oakland, Pontiac, MI USA. [Gastman, I.] Waterford Med Associates PC, Waterford, MI USA. [Gupta, V.] Borgess Res Inst Borgess Cardiovasc Res, Kalamazoo, MI USA. [Longshaw, K.] Texas Hlth Phys Grp, Dallas, TX USA. [Gonzalez-Campoy, J. M.] MNCOME Fdn, Eagan, MN USA. [Raikhel, M.] Torrance Clin Res, Lomita, CA USA. [Thomas, J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Wood, K.] Belleville Family Med Associates Ltd, Belleville, IL USA. [Diab, I.] Paramount Med Res & Consulting LLC, Middleburg Hts, OH USA. [Furda, J.] Minneapolis Heart Inst, Baxter, MN USA. [Gelernt, M.] Cardiovasc Associates Delaware Valley PA, Elmer, NJ USA. [Halter, M.] Ilumina Clin Associates, Tyrone, PA USA. [House, B.] Am Hlth Network Indiana LLC, Fishers, IN USA. [Kaster, S.] Wenatchee Valley Med Ctr, Wenatchee, WA USA. [Raad, G.] PMG Res Charlotte, Charlotte, NC USA. [Stamatin, R.] Remedica LLC, Rochester, MI USA. [Barker, B.] Delaware Smith Clin, Delaware, OH USA. [Blonder, R.] Colorado Hlth Med Grp, Colorado Springs, CO USA. [Calderon, R. Burgos] RCMI Clin Res Ctr, Rio Piedras, PR USA. [Carrol, A.] Ctr Thyroid Dis & Endocrinol, Beachwood, OH USA. [Comerota, A.] Jobst Vasc Ctr, Toledo, OH USA. [Feinglos, M.] Duke Univ, Med Ctr, Durham, NC USA. [Henderson, D.] Cardiol Res Associates, Daytona Beach, FL USA. [Kastelic, R.] Ilumina Clin Associates, Johnstown, PA USA. [Talano, J.] Southwest Florida Res LLC, Naples, FL USA. [Lee, P. Ver] EMMC Northeast Cardiol Associates, Bangor, ME USA. [Brosseau, J.] Altru Hlth Syst, Grand Forks, ND USA. [Clark, W.] Oregon Hlth & Sci Univ, Oregon Stroke Ctr, Portland, OR 97201 USA. [Cohen, E.] Metab Res Inst, Boynton Beach, FL USA. [Fialkow, J.] Cardiovasc Res Ctr South Florida, Miami, FL USA. [Horton, K.] IMED Healthcare Associated PLLC, San Antonio, TX USA. [Kozman, H.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [McGill, J.] Washington Univ, St Louis, MO USA. [Mihills, C.] Southlake Clin Trials, Southlake, TX USA. [Poonawala, R.] Family Practice Ctr South, Austin, TX USA. [Shore, K.] Med Clin North Texas, Plano, TX USA. [Tejada, L.] St Lukes Hosp & Hlth Network, Bethlehem, PA USA. [Torres, R.] Caribbean Clin Trials Corp, San Juan, PR USA. [Wright, W.] Esse Hlth Cardiol Consultants, St Louis, MO USA. [Calatayud, G.] Del Rosario Med Ctr Inc, Huntington Pk, CA USA. [Chandna, H.] Victoria Heart & Vasc Ctr, Victoria, TX USA. [Drozdiak, R.] Ilumina Clin Associates, Clymer, PA USA. [Fink, R.] Diabet & Endocrine Associates, La Mesa, CA USA. [Gill, R.] Virginia Commonwealth Univ, Richmond, VA USA. [Glandt, M.] Bronx Lebanon Hosp Ctr, Bronx, NY 10456 USA. [Hack, T.] Primary Care Cardiol Res Inc, Ayer, MA USA. [Kay, J.] Clin Res Advantage Inc, Ridge Family Practice, Council Bluffs, IA USA. [Mansouri, V.] St Thomas Res Inst, Nashville, TN USA. [McKnight, T.] Prairie Fields Family Med PC, Fremont, NE USA. [Mostel, E.] Palm Beach Gardens Res Ctr LLC, Palm Beach Gardens, FL USA. [Schmidt, L.] Genova Clin Res, Tucson, AZ USA. [Seide, H.] Daytona Heart Grp, Daytona Beach, FL USA. [Sonel, E.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Taylor, R.] North Mem Heart & Vasc Inst, Robbinsdale, MN USA. [Velasquez, M.] George Washington Univ, Med Faculty Associates, Washington, DC USA. [Bretton, E.] Albuquerque Clin Trials Inc, Albuquerque, NM USA. [Feldman, R.] MediQuest Res Grp Inc, Munroe Reg Med Ctr, Ocala, FL USA. [Hartman, A.] Virginia Res Ctr LLC, Midlothian, VA USA. [Hershon, K.] North Shore Diabet & Endocrine Associates, New Hyde Pk, NY USA. [Martin, E.] Martin Diagnost Clin, Tomball, TX USA. [Mohiuddin, F.] Apollo Med Res LTD, Niles, IL USA. [Naygandhi, Y.] Northwest Med Care PA, Houston, TX USA. [Riske, T.] Hayden Lake Family Phys, Hayden Lake, ID USA. [Schima, S.] Creighton Univ, Cardiac Ctr, Omaha, NE 68178 USA. [Uzoaga, E. R.] Oxford Clin Res LLC, Houston, TX USA. [Ward, H.] Clin Res Works LLC, Southington, CT USA. [Weinstock, R.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Williams, T.] Texas Hlth Phys Grp, Irving, TX USA. [Altschuller, A.] Hawthorn Med Associates, N Dartmouth, MA USA. [Aoki, T.] Aoki Diabet Res Inst, Sacramento, CA USA. [Blumenthal, S.] Zablocki VAMC, Milwaukee, WI USA. [Cash, A.] Ilumina Clin Associates, Indiana, PA USA. [Gutmann, J.] Deaconess Clin Inc, Evansville, IN USA. [Hagan, M.] Montana Hlth Res Inst Inc, Billings, MT USA. [Kabour, A.] Cardiovasc Res Ctr LLC, Toledo, OH USA. [Markus, T.] Dayton Heart Ctr, Dayton, OH USA. [McKenzie, W.] M&O Clin Res LLC, Ft Lauderdale, FL USA. [Moursi, M.] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. [Mystkowski, P.] Hope Heart Inst, Bellevue, WA USA. [Ovalle, F.] Univ Alabama Birmingham, Birmingham, AL USA. [Perkins, R.] Texas Hlth Phys Grp, Grapevine, TX USA. [Popeil, L.] Magnolia Res Grp Inc, Ocala, FL USA. [Saniuk, R.] Bellevue Family Practice PC, Clin Res Advantage Inc, Bellevue, NE USA. [Sierra, Y.] Med Interna, Toa Baja, PR USA. [Alvarado, O.] Med Grp Texas, Ft Worth, TX USA. [Anderson, J.] Integris Cardiovasc Phys LLC, Oklahoma City, OK USA. [Bajaj, M.] Baylor Coll Med, Houston, TX 77030 USA. [Blank, R.] Presbyterian Novant Heart & Wellness, Southern Peidmont Primary Care, Monroe, NC USA. [Chu, A.] Amarillo Heart Clin Res Inst Inc, Amarillo, TX USA. [Levinsky, L.] CPL Associates LLC, Buffalo, NY USA. [Levy, P.] Phoenix Endocrinol Clin Ltd, Phoenix, AZ USA. [Osborne, J.] State Heart Cardiol, Grapevine, TX USA. [Pavon, H.] Internal Med Kidney & Hypertens Ctr, Norfolk, VA USA. [Sanderlin, D.] Lone Star Clin Res, Houston, TX USA. [Schaer, G.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Zarich, S.] Bridgeport Hosp, Bridgeport, CT USA. [Atassi, K.] Northwest Indiana Cardiovasc Phys PC, Valparaiso, IN USA. [Bayron, C.] Intervent Cardiac Consultants PLC, Trinity, FL USA. [Casagrande, M.] West Houston Area Clin Trial Consultants LLC, Houston, TX USA. [Das, D.] St Vincent Heart Clin Arkansas, Little Rock, AR USA. [Gimness, M.] Clin Res Cent Florida, Plant City, FL USA. [Handel, F.] Schuster Cardiol Associates Inc, Kettering, OH USA. [Kinstrey, T.] Family Med Clin, Shreveport, LA USA. [Leu, S.] Baptist Heart Specialists, Jacksonville, FL USA. [Osei, K.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Nouel, J. Soba] Jose M Soba Med Gen, Juncos, PR USA. [Soltani, Z.] LSU Hlth Sci Ctr, Dept Internal Med, Sect Nephrol & Hypertens, Kenner, LA USA. [Sussman, H.] Icon Clin Trials, Pembroke Pines, FL USA. [Chiu, K.] City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA. [Duda, R., Jr.] Oklahoma Heart Inst, Tulsa, OK USA. [Farnsworth, K.] Northern Indiana Res Alliance, Ft Wayne, IN USA. [Lano, M.] Ridgeview Res, Chaska, MN USA. [Lee, F.] Guthrie Clin Ltd, Sayre, PA USA. [Lee, F.] Robert Packer Hosp, Sayre, PA USA. [Levin, P.] MODEL Clin Res, Baltimore, MD USA. [Pratt, S.] West Coast Res LLC, San Ramon, CA USA. [Richwine, R.] Hlth Phys Grp, Ft Worth, TX USA. [Ruiz-Rivera, L.] Endocrine Lipid Diabet Res Inst, Ponce, PR USA. [Turner, J.] Cardiac Wellness Consultants SC, Chicago, IL USA. [Wood, J.] Texas Hlth Phys Grp, Richardson, TX USA. [Colon, Carlos Benitez] Dr Carlos Benitez Colon Med Interna, San Juan, PR USA. [Demattia, J.] JVC Family Med, Houston, TX USA. [Desai, V.] Charles River Med Associates, Natick, MA USA. [Fitz-Patrick, D.] East West Med Res Inst, Honolulu, HI USA. [Goral, S.] Univ Penn, Philadelphia, PA 19104 USA. [Odhav, A.] West Houston Area Clin Trial Consultants LLC, Houston, TX USA. [Prentiss, A.] Prentiss Family Med, Colleyville, TX USA. [Ruff, C.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Wu, W.] Cent Cardiovasc Res Fdn, San Antonio, TX USA. [Wyne, K.] Methodist Hosp, Res Inst, 6535 Fannin, Houston, TX 77030 USA. [Applegate, R.] Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. [Cabral, J.] Cleveland Clin Florida, Weston, FL USA. [Kotha, P.] Purushotham & Akther Kotha MD Inc, La Mesa, CA USA. [Ortega, P.] Cent Florida Primary Care, Winter Pk, FL USA. [Simmons, D.] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA. EM dlbhattmd@post.harvard.edu RI Ma, Ronald/C-2788-2009; Delgado, Elias/B-2634-2013; Kubica, Jacek/D-6906-2014; Arkhipov, Mikhail/Q-2316-2015; Lerch, Markus M./E-2206-2016; Colquhoun, David/F-9078-2013; Mauricio, Didac/B-7951-2009; De Cosmo, Salvatore/J-7420-2016; Del Prato, Stefano/K-3405-2016; Muirhead, Norman/G-3337-2011; Miller, Elzbieta/S-9249-2016; Kobalava, Zhanna/S-3842-2016; Svacina, Stepan/C-1962-2017; Gutmann, Jochen/A-5103-2009; OI Ma, Ronald/0000-0002-1227-803X; Delgado, Elias/0000-0001-6114-9712; Lerch, Markus M./0000-0002-9643-8263; Mauricio, Didac/0000-0002-2868-0250; De Cosmo, Salvatore/0000-0001-8787-8286; Del Prato, Stefano/0000-0002-5388-0270; Svacina, Stepan/0000-0002-0894-4116; Ametov, A.S./0000-0002-7936-7619; Oschepkova, Elena/0000-0003-4534-9890; Gutmann, Jochen/0000-0002-1394-9202; Mazurek, Tomasz/0000-0002-3693-8741 FU AstraZeneca; Bristol-Myers Squibb FX Funded by AstraZeneca and Bristol-Myers Squibb NR 35 TC 866 Z9 904 U1 41 U2 184 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 OCT 3 PY 2013 VL 369 IS 14 BP 1317 EP 1326 DI 10.1056/NEJMoa1307684 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 227KI UT WOS:000325111200009 PM 23992601 ER PT J AU Kapoor, R Johnson, RA AF Kapoor, Roger Johnson, Richard A. TI Porphyria Cutanea Tarda and Hypertrichosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material AB A 54-year-old woman with hepatitis C infection presented with excess hair on her face, which she had had since the age of 25 years, and new erosions on her hands. Several ulcerations, milia, and thickened skin were noted on the dorsal aspect of her hands. A 54-year-old woman who had had hepatitis C infection for 12 years presented with excess hair on her face, which she had had since the age of 25 years, and new erosions on her hands. On physical examination, several ulcerations, milia, and thickened skin were noted on the dorsal aspect of both hands (Panel A). Excess hair growth (hypertrichosis) was noted in the temporal and malar facial areas (Panel B). Laboratory studies revealed an elevated level of 24-hour urinary porphyrin of 707 g (851 nmol; normal, <30 g [36 nmol]). Porphyria cutanea tarda refers to a group of anomalies in ... C1 [Kapoor, Roger] Beloit Hlth Syst, Beloit, WI USA. [Johnson, Richard A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kapoor, R (reprint author), Beloit Hlth Syst, Beloit, WI USA. EM rogerkapoor@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 3 PY 2013 VL 369 IS 14 BP 1356 EP 1356 DI 10.1056/NEJMicm1010902 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 227KI UT WOS:000325111200013 PM 24088095 ER PT J AU Greene, MF AF Greene, Michael F. TI Delivering Twins SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RETROSPECTIVE COHORT; PERINATAL DEATH; BIRTHS; RISK AB The rate of twin births in the United States has risen 76% from 1980 through 2009-2011. The rate of rise was particularly steep from the early 1990s through the early 2000s and seems to have reached a plateau of approximately 33.2 twin births per 1000 deliveries in the period from 2009 through 2011.(1) The incidence of naturally occurring twin pregnancy rises with increasing maternal age, and the age of women having babies in the United States has risen steadily from 20% of all births among women 30 years of age or older in 1980 to more than 35% for the ... C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Greene, MF (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 3 PY 2013 VL 369 IS 14 BP 1365 EP 1366 DI 10.1056/NEJMe1310744 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 227KI UT WOS:000325111200015 PM 24088097 ER PT J AU Korboe, AA Carney, J AF Korboe, Akosua A. Carney, Julia TI Mental Health and the Global Agenda SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Korboe, Akosua A.] Univ Rochester Sch Med & Dent, Rochester, NY USA. [Carney, Julia] Massachusetts Gen Hosp, Boston, MA USA. RP Korboe, AA (reprint author), Univ Rochester Sch Med & Dent, Rochester, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 3 PY 2013 VL 369 IS 14 BP 1380 EP 1380 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 227KI UT WOS:000325111200030 PM 24088112 ER PT J AU Ortega, F Counter, SA Buchanan, LH Parra, AMC Collaguaso, MA Jacobs, AB AF Ortega, Fernando Counter, S. Allen Buchanan, Leo H. Coronel Parra, Angelica Maria Angela Collaguaso, Maria Jacobs, Anthony B. TI TRACKING BLOOD LEAD AND ZINC PROTOPORPHYRIN LEVELS IN ANDEAN ADULTS WORKING IN A LEAD CONTAMINATED ENVIRONMENT SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID BREAST-MILK; COMET ASSAY; DNA-DAMAGE; EXPOSURE; WORKERS; CHILDREN; PERFORMANCE AB The purpose of this study was to investigate current blood lead (PbB) and zinc protoporphyrin (ZPP) levels in adults presently living in environmentally Pb-contaminated Andean communities, and to compare the findings with the PbB and ZPP levels of Pb-exposed adult cohorts from the same study area tested between 1996 and 2007. Blood samples from 39 adults were measured for PbB and ZPP concentrations. The current mean PbB level (22.7 g/dl) was significantly lower than the mean (37.9 g/dl) of the initial 1996 cohort. PbB levels for the 1997, 1998, 2003, and 2006 cohorts were also significantly lower than the levels for the 1996 group. Elevated ZPP/heme ratios of 103.3, 128.4, and 134.2 mol/mol were not significantly different for the 2006, 2007, and 2012 groups, indicating chronic Pb exposure. While ZPP levels of Andean Ecuadorian Pb-glazing workers have remained elevated, PbB levels declined. Lead exposure of the workers needs to be continually monitored. C1 [Ortega, Fernando] Colegio Ciencias Salud, Escuela Med, Escuela Salud Publ,Inst Arts & Sci GAIAS, Colegio Artes Liberales & Galapagos, Quito, Ecuador. [Ortega, Fernando] Univ San Francisco Quito, Quito, Ecuador. [Counter, S. Allen] Harvard Univ, Sch Med, Biol Labs, Dept Neurol, Cambridge, MA 02138 USA. [Counter, S. Allen] Massachusetts Gen Hosp, Dept Neurophysiol, Boston, MA 02114 USA. [Buchanan, Leo H.] Univ Massachusetts, Sch Med, Eunice Kennedy Shriver Ctr, Dept Pediat, Waltham, MA USA. [Buchanan, Leo H.] Harvard Univ, Hlth Serv, Dept Otolaryngol, Cambridge, MA 02138 USA. [Coronel Parra, Angelica Maria; Angela Collaguaso, Maria] Subctr Salud, Pujili, Cotopaxi, Ecuador. [Jacobs, Anthony B.] Harvard Biol Labs, Cambridge, MA USA. RP Counter, SA (reprint author), Harvard Univ, Sch Med, Biol Labs, Dept Neurol, 16 Divin Ave, Cambridge, MA 02138 USA. EM allen_counter@harvard.edu FU National Institutes of Health (NIH) [P30 HD04147] FX LHB is supported in part by National Institutes of Health (NIH) grant P30 HD04147. NR 37 TC 7 Z9 7 U1 1 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 EI 1087-2620 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD OCT 2 PY 2013 VL 76 IS 19 BP 1111 EP 1120 DI 10.1080/15287394.2013.840708 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 256FE UT WOS:000327294300003 PM 24274152 ER PT J AU Samur, MK Shah, PK Wang, XJ Minvielle, S Magrangeas, F Avet-Loiseau, H Munshi, NC Li, C AF Samur, Mehmet K. Shah, Parantu K. Wang, Xujun Minvielle, Stephane Magrangeas, Florence Avet-Loiseau, Herve Munshi, Nikhil C. Li, Cheng TI The shaping and functional consequences of the dosage effect landscape in multiple myeloma SO BMC GENOMICS LA English DT Article DE Copy number alteration; Dosage effect; Multiple myeloma; Hyperdiploid; Integrative genomics ID GENE-EXPRESSION; COPY-NUMBER; INTEGRATIVE ANALYSIS; ANALYSIS REVEALS; CANCER; ANEUPLOIDY; SURVIVAL; LEUKEMIA; IDENTIFICATION; TUMORIGENESIS AB Background: Multiple myeloma (MM) is a malignant proliferation of plasma B cells. Based on recurrent aneuploidy such as copy number alterations (CNAs), myeloma is divided into two subtypes with different CNA patterns and patient survival outcomes. How aneuploidy events arise, and whether they contribute to cancer cell evolution are actively studied. The large amount of transcriptomic changes resultant of CNAs (dosage effect) pose big challenges for identifying functional consequences of CNAs in myeloma in terms of specific driver genes and pathways. In this study, we hypothesize that gene-wise dosage effect varies as a result from complex regulatory networks that translate the impact of CNAs to gene expression, and studying this variation can provide insights into functional effects of CNAs. Results: We propose gene-wise dosage effect score and genome-wide karyotype plot as tools to measure and visualize concordant copy number and expression changes across cancer samples. We find that dosage effect in myeloma is widespread yet variable, and it is correlated with gene expression level and CNA frequencies in different chromosomes. Our analysis suggests that despite the enrichment of differentially expressed genes between hyperdiploid MM and non-hyperdiploid MM in the trisomy chromosomes, the chromosomal proportion of dosage sensitive genes is higher in the non-trisomy chromosomes. Dosage-sensitive genes are enriched by genes with protein translation and localization functions, and dosage resistant genes are enriched by apoptosis genes. These results point to future studies on differential dosage sensitivity and resistance of pro-and anti-proliferation pathways and their variation across patients as therapeutic targets and prognosis markers. Conclusions: Our findings support the hypothesis that recurrent CNAs in myeloma are selected by their functional consequences. The novel dosage effect score defined in this work will facilitate integration of copy number and expression data for identifying driver genes in cancer genomics studies. The accompanying R code is available at http://www.canevolve.org/dosageEffect/. C1 [Samur, Mehmet K.; Shah, Parantu K.; Li, Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Samur, Mehmet K.; Shah, Parantu K.; Li, Cheng] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Samur, Mehmet K.] Akdeniz Univ, Dept Biostat & Med Informat, TR-07058 Antalya, Turkey. [Wang, Xujun] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. [Minvielle, Stephane; Magrangeas, Florence; Avet-Loiseau, Herve] Univ Nantes, INSERM, CNRS 6299, UMR892, Nantes, France. [Minvielle, Stephane; Magrangeas, Florence; Avet-Loiseau, Herve] CHU Nantes, Unite Mixte Genom Canc, F-44035 Nantes 01, France. [Munshi, Nikhil C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02215 USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM Nikhil_Munshi@dfci.harvard.edu; lch3000@gmail.com RI Magrangeas, Florence/L-3080-2015; Minvielle, Stephane/K-8251-2015 FU NIH [R01 GM077122]; National Basic Research Program of China (973 Program) [2010CB944904]; Claudia Adams Barr Program in Innovative Basic Cancer Research; Multiple Myeloma Career Development award; National Institutes of Health [RO1-124929, PO1-155258, P50-100007, PO1-78378]; Dept. of Veterans Affairs Merit Review Awards; French National Research Agency [R08079NS] FX Grant support are from NIH R01 GM077122 (C Li), National Basic Research Program of China (973 Program; No. 2010CB944904) (X Wang), and Claudia Adams Barr Program in Innovative Basic Cancer Research and the Multiple Myeloma Career Development award (PK Shah). This work is also supported in part by grants from the National Institutes of Health Grants RO1-124929, PO1-155258, P50-100007 and PO1-78378 to NC Munshi and C Li and from the Dept. of Veterans Affairs Merit Review Awards to NC Munshi. S Minvielle and F Magrangeas were supported by French National Research Agency, Grant R08079NS. NR 43 TC 6 Z9 6 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD OCT 2 PY 2013 VL 14 AR 672 DI 10.1186/1471-2164-14-672 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 241NJ UT WOS:000326173600001 PM 24088394 ER PT J AU Zhang, JM Fang, SNC Mittleman, MA Christiani, DC Cavallari, JM AF Zhang, Jinming Fang, Shona C. Mittleman, Murray A. Christiani, David C. Cavallari, Jennifer M. TI Secondhand tobacco smoke exposure and heart rate variability and inflammation among non-smoking construction workers: a repeated measures study SO ENVIRONMENTAL HEALTH LA English DT Article DE Secondhand smoke; Tobacco; Autonomic nervous system; Heart rate variability; Inflammatory marker ID PARTICULATE AIR-POLLUTION; SUDDEN CARDIAC DEATH; CARDIOVASCULAR-DISEASE; CIGARETTE-SMOKING; PASSIVE SMOKING; NEVER-SMOKERS; UNITED-STATES; POPULATION; PARTICLES; COHORT AB Background: Although it has been well recognized that exposure to secondhand tobacco smoke (SHS) is associated with cardiovascular mortality, the mechanisms and time course by which SHS exposure may lead to cardiovascular effects are still being explored. Methods: Non-smoking workers were recruited from a local union and monitored inside a union hall while exposed to SHS over approximately 6 hours. Participants were fitted with a continuous electrocardiographic monitor upon enrollment which was removed at the end of a 24-hr monitoring period. A repeated measures study design was used where resting ECGs and blood samples were taken from individuals before SHS exposure (baseline), immediately following SHS exposure (post) and the morning following SHS exposure (next-morning). Inflammatory markers, including high sensitivity C-reactive protein (CRP) and white blood cell count (WBC) were analyzed. Heart rate variability (HRV) was analyzed from the ECG recordings in time (SDNN, rMSSD) and frequency (LF, HF) domain parameters over 5-minute periods. SHS exposure was quantified using a personal fine particulate matter (PM2.5) monitor. Linear mixed effects regression models were used to examine within-person changes in inflammatory and HRV parameters across the 3 time periods. Exposure-response relationships with PM2.5 were examined using mixed effects models. All models were adjusted for age, BMI and circadian variation. Results: A total of 32 male non-smokers were monitored between June 2010 and June 2012. The mean PM2.5 from SHS exposure was 132 mu g/m(3). Immediately following SHS exposure, a 100 mu g/m(3) increase in PM2.5 was associated with declines in HRV (7.8% [ standard error (SE) = 3%] SDNN, 8.0% (SE = 3.9%) rMSSD, 17.2% (SE = 6.3%) LF, 29.0% (SE = 10.1%) HF) and increases in WBC count 0.42 (SE = 0.14) k/mu l. Eighteen hours following SHS exposure, a 100 mu g/m(3) increase in PM2.5 was associated with 24.2% higher CRP levels. Conclusions: Our study suggest that short-term SHS exposure is associated with significantly lower HRV and higher levels of inflammatory markers. Exposure-associated declines in HRV were observed immediately following exposure while higher levels of CRP were not observed until 18 hours following exposure. Cardiovascular autonomic and inflammation responses may contribute to the pathophysiologic pathways that link SHS exposure with adverse cardiovascular outcomes. C1 [Zhang, Jinming; Fang, Shona C.; Christiani, David C.; Cavallari, Jennifer M.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Cavallari, Jennifer M.] Univ Connecticut Hlth Ctr, Div Occupat & Environm Med, Farmington, CT USA. [Mittleman, Murray A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Mittleman, Murray A.; Christiani, David C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Cardiovasc Epidemiol Res Unit, Sch Med, Boston, MA 02215 USA. [Fang, Shona C.] New England Res Inst Inc, Watertown, MA USA. RP Cavallari, JM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. EM CAVALLARI@uchc.edu FU Flight Attendants Medical Research Institute Young Clinical Scientist Award; NIEHS [ES009860, ES00002, T32 ES 07069] FX The study is supported by the Flight Attendants Medical Research Institute Young Clinical Scientist Award and NIEHS ES009860, ES00002, T32 ES 07069. The authors would like to thank Angela Fan, Cali Chang, Li Su, Mike Wang, Rachel Grashow, Rihong Zai and the International Brotherhood of Boilermakers, Local 29, Quincy MA, USA. NR 38 TC 5 Z9 5 U1 1 U2 18 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-069X J9 ENVIRON HEALTH-GLOB JI Environ. Health PD OCT 2 PY 2013 VL 12 AR 83 DI 10.1186/1476-069X-12-83 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 242YX UT WOS:000326284000001 PM 24083379 ER PT J AU Desikan, RS Thompson, WK Holland, D Hess, CP Brewer, JB Zetterberg, H Blennow, K Andreassen, OA McEvoy, LK Hyman, BT Dale, AM AF Desikan, Rahul S. Thompson, Wesley K. Holland, Dominic Hess, Christopher P. Brewer, James B. Zetterberg, Henrik Blennow, Kaj Andreassen, Ole A. McEvoy, Linda K. Hyman, Bradley T. Dale, Anders M. CA Alzheimer's Dis Neuroimaging Initi TI Heart fatty acid binding protein and A beta-associated Alzheimer's neurodegeneration SO MOLECULAR NEURODEGENERATION LA English DT Article DE Alzheimer's disease; Fatty acids; Lipids; Amyloid; Tau; Brain atrophy ID CEREBROSPINAL-FLUID; CHOLESTEROL LEVEL; CEREBRAL-CORTEX; MOUSE MODEL; STATIN USE; DISEASE; PLASMA; DEMENTIA; BRAIN; OVEREXPRESSION AB Background: Epidemiological and molecular findings suggest a relationship between Alzheimer's disease (AD) and dyslipidemia, although the nature of this association is not well understood. Results: Using linear mixed effects models, we investigated the relationship between CSF levels of heart fatty acid binding protein (HFABP), a lipid binding protein involved with fatty acid metabolism and lipid transport, amyloid beta (A beta), phospho-tau, and longitudinal MRI-based measures of brain atrophy among 295 non-demented and demented older individuals. Across all participants, we found a significant association of CSF HFABP with longitudinal atrophy of the entorhinal cortex and other AD-vulnerable neuroanatomic regions. However, we found that the relationship between CSF HABP and brain atrophy was significant only among those with low CSF A beta(1-42) and occurred irrespective of phospho-tau(181p) status. Conclusions: Our findings indicate that A beta associated volume loss occurs in the presence of elevated HFABP irrespective of phospho-tau. This implicates a potentially important role for fatty acid binding proteins in Alzheimer's disease neurodegeneration. C1 [Desikan, Rahul S.; Brewer, James B.; McEvoy, Linda K.; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92037 USA. [Thompson, Wesley K.; Andreassen, Ole A.; Dale, Anders M.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92037 USA. [Holland, Dominic; Brewer, James B.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92037 USA. [Hess, Christopher P.] Univ Calif San Diego, Neuroradiol Sect, Dept Radiol & Biomed Imaging, San Francisco, CA 92093 USA. [Zetterberg, Henrik; Blennow, Kaj] Goteburg Univ, Sahlgrenska Acad, Clin Neurochem Lab, S-40530 Molndal, Sweden. [Zetterberg, Henrik] UCL Inst Neurol, London WC1N 3BG, England. [Andreassen, Ole A.] Univ Oslo, Inst Clin Med, Oslo, Norway. [Andreassen, Ole A.] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway. [Hyman, Bradley T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Desikan, RS (reprint author), Univ Calif San Diego, Dept Radiol, 8950 Villa La Jolla Dr,Suite C101, La Jolla, CA 92037 USA. EM rdesikan@ucsd.edu FU National Institutes of Health [R01AG031224, K01AG029218, K02 NS067427, T32 EB005970]; Research Council of Norway [183782/V50]; South East Norway Health Authority [2010-074]; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; 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; NIH [P30 AG010129, K01 AG030514] FX This research was supported by grants from the National Institutes of Health (R01AG031224; K01AG029218; K02 NS067427; T32 EB005970), the Research Council of Norway (183782/V50) and the South East Norway Health Authority (2010-074). Data collection and sharing for this project was 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:; 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 California, Los Angeles. This research was also supported by NIH grants P30 AG010129 and K01 AG030514. NR 39 TC 10 Z9 10 U1 0 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-1326 J9 MOL NEURODEGENER JI Mol. Neurodegener. PD OCT 2 PY 2013 VL 8 AR 39 DI 10.1186/1750-1326-8-39 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 237JK UT WOS:000325865500001 PM 24088526 ER PT J AU Walton, E Geisler, D Hass, J Liu, JY Turner, J Yendiki, A Smolka, MN Ho, BC Manoach, DS Gollub, RL Roessner, V Calhoun, VD Ehrlich, S AF Walton, Esther Geisler, Daniel Hass, Johanna Liu, Jingyu Turner, Jessica Yendiki, Anastasia Smolka, Michael N. Ho, Beng-Choon Manoach, Dara S. Gollub, Randy L. Roessner, Veit Calhoun, Vince D. Ehrlich, Stefan TI The Impact of Genome-Wide Supported Schizophrenia Risk Variants in the Neurogranin Gene on Brain Structure and Function SO PLOS ONE LA English DT Article ID DORSOLATERAL PREFRONTAL CORTEX; WORKING-MEMORY PERFORMANCE; LONG-TERM POTENTIATION; ENCODING NEUROGRANIN; CEREBRAL-CORTEX; FLIP-FLOP; ASSOCIATION; DYSFUNCTION; FMRI; METAANALYSIS AB The neural mechanisms underlying genetic risk for schizophrenia, a highly heritable psychiatric condition, are still under investigation. New schizophrenia risk genes discovered through genome-wide association studies (GWAS), such as neurogranin (NRGN), can be used to identify these mechanisms. In this study we examined the association of two common NRGN risk single nucleotide polymorphisms (SNPs) with functional and structural brain-based intermediate phenotypes for schizophrenia. We obtained structural, functional MRI and genotype data of 92 schizophrenia patients and 114 healthy volunteers from the multisite Mind Clinical Imaging Consortium study. Two schizophrenia-associated NRGN SNPs (rs12807809 and rs12541) were tested for association with working memory-elicited dorsolateral prefrontal cortex (DLPFC) activity and surface-wide cortical thickness. NRGN rs12541 risk allele homozygotes (TT) displayed increased working memory-related activity in several brain regions, including the left DLPFC, left insula, left somatosensory cortex and the cingulate cortex, when compared to non-risk allele carriers. NRGN rs12807809 non-risk allele (C) carriers showed reduced cortical gray matter thickness compared to risk allele homozygotes (TT) in an area comprising the right pericalcarine gyrus, the right cuneus, and the right lingual gyrus. Our study highlights the effects of schizophrenia risk variants in the NRGN gene on functional and structural brain-based intermediate phenotypes for schizophrenia. These results support recent GWAS findings and further implicate NRGN in the pathophysiology of schizophrenia by suggesting that genetic NRGN risk variants contribute to subtle changes in neural functioning and anatomy that can be quantified with neuroimaging methods. C1 [Walton, Esther; Geisler, Daniel; Hass, Johanna; Roessner, Veit; Ehrlich, Stefan] Tech Univ Dresden, Dept Child & Adolescent Psychiat, Univ Hosp Carl Gustav Carus, Dresden, Germany. [Liu, Jingyu; Turner, Jessica; Calhoun, Vince D.] MIND Res Network, Albuquerque, NM USA. [Liu, Jingyu; Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Yendiki, Anastasia; Manoach, Dara S.; Gollub, Randy L.; Ehrlich, Stefan] Massachusetts Gen Hosp, MGH MIT HMS Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Smolka, Michael N.] Tech Univ Dresden, Dept Psychiat & Psychotherapy, Dresden, Germany. [Smolka, Michael N.] Tech Univ Dresden, Neuroimaging Ctr, Dept Psychol, Dresden, Germany. [Ho, Beng-Choon] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Manoach, Dara S.; Gollub, Randy L.; Ehrlich, Stefan] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Ehrlich, S (reprint author), Tech Univ Dresden, Dept Child & Adolescent Psychiat, Univ Hosp Carl Gustav Carus, Dresden, Germany. EM transden.lab@uniklinikum-dresden.de RI Ho, Beng-Choon/D-6959-2011; Smolka, Michael/B-4865-2011; Turner, Jessica/H-7282-2015; OI Ho, Beng-Choon/0000-0003-3976-1555; Smolka, Michael/0000-0001-5398-5569; Turner, Jessica/0000-0003-0076-8434; Ehrlich, Stefan/0000-0003-2132-4445; Gollub, Randy L./0000-0002-9434-4044; Walton, Esther/0000-0002-0935-2200; Liu, Jingyu/0000-0002-1724-7523 FU National Institutes of Health (NIH/NCRR) [P41RR14075]; Department of Energy [DE-FG02-99ER62764]; Mind Research Network, Morphometry BIRN [1U24, RR021382A]; Function BIRN [U24RR021992]; NIH.NCRR [MO1 RR025758-01]; NIMH [1RC1MH089257, 2 R01MH067720]; NIH/NIBIB [K99/R00]; Deutsche Forschungsgemeinschaft; NARSAD Young Investigator Grant; Friedrich-Ebert Stiftung; [EB008129] FX This work was supported by the National Institutes of Health (NIH/NCRR P41RR14075), Department of Energy (DE-FG02-99ER62764), Mind Research Network, Morphometry BIRN (1U24, RR021382A), Function BIRN (U24RR021992-01, NIH.NCRR MO1 RR025758-01, NIMH 1RC1MH089257 to VDC), 2 R01MH067720 (DSM), NIH/NIBIB K99/R00 Pathway to Independence award EB008129 (AY), the Deutsche Forschungsgemeinschaft (research fellowship to SE), the NARSAD Young Investigator Grant (to SE) and the Friedrich-Ebert Stiftung (stipend to EW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 70 TC 9 Z9 9 U1 1 U2 20 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 OCT 2 PY 2013 VL 8 IS 10 AR e76815 DI 10.1371/journal.pone.0076815 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 231RG UT WOS:000325434500086 PM 24098564 ER PT J AU Day, ML Delgutte, B AF Day, Mitchell L. Delgutte, Bertrand TI Decoding Sound Source Location and Separation Using Neural Population Activity Patterns SO JOURNAL OF NEUROSCIENCE LA English DT Article ID INTERAURAL TIME DIFFERENCES; INFERIOR COLLICULUS; LOCALIZATION ACUITY; CORTICAL-NEURONS; CUES; CAT; SENSITIVITY; AZIMUTH; MODEL; CODE AB The strategies by which the central nervous system decodes the properties of sensory stimuli, such as sound source location, from the responses of a population of neurons are a matter of debate. We show, using the average firing rates of neurons in the inferior colliculus (IC) of awake rabbits, that prevailing decoding models of sound localization (summed population activity and the population vector) fail to localize sources accurately due to heterogeneity in azimuth tuning across the population. In contrast, a maximum-likelihood decoder operating on the pattern of activity across the population of neurons in one IC accurately localized sound sources in the contralateral hemifield, consistent with lesion studies, and did so with a precision consistent with rabbit psychophysical performance. The pattern decoder also predicts behavior in response to incongruent localization cues consistent with the long-standing "duplex" theory of sound localization. We further show that the pattern decoder accurately distinguishes two concurrent, spatially separated sources from a single source, consistent with human behavior. Decoder detection of small amounts of source separation directly in front is due to neural sensitivity to the interaural decorrelation of sound, at both low and high frequencies. The distinct patterns of IC activity between single and separated sound sources thereby provide a neural correlate for the ability to segregate and localize sources in everyday, multisource environments. C1 [Day, Mitchell L.; Delgutte, Bertrand] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. [Day, Mitchell L.; Delgutte, Bertrand] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Delgutte, Bertrand] MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Day, ML (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. EM day@meei.harvard.edu OI Day, Mitchell/0000-0002-2754-234X; , /0000-0003-1349-9608 FU National Institute on Deafness and Other Communication Disorders [R01 DC002258, P30 DC005209] FX This work was supported by National Institute on Deafness and Other Communication Disorders grants R01 DC002258 and P30 DC005209. We thank Ross Williamson, Ken Hancock, and Dan Polley for a critical reading of an earlier version of this manuscript. NR 41 TC 14 Z9 14 U1 0 U2 14 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 2 PY 2013 VL 33 IS 40 BP 15837 EP 15847 DI 10.1523/JNEUROSCI.2034-13.2013 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 229RA UT WOS:000325283600018 PM 24089491 ER PT J AU Lai, PS Thompson, BT AF Lai, Peggy S. Thompson, B. Taylor TI Why Activated Protein C Was Not Successful in Severe Sepsis and Septic Shock: Are We Still Tilting at Windmills? SO CURRENT INFECTIOUS DISEASE REPORTS LA English DT Article DE Sepsis; Septic shock; Systemic inflammatory response syndrome; Drotrecogin alfa activated; Protein C ID RANDOMIZED CONTROLLED-TRIAL; PROPENSITY-MATCHED ANALYSIS; PULMONARY-ARTERY CATHETERS; INTENSIVE-CARE UNITS; CLINICAL EFFECTIVENESS; OUTCOMES; PROGRAM; ADULTS; METAANALYSIS; MANAGEMENT AB Drotrecogin alpha activated (DAA), trade name Xigris, is a recombinant human protein C that has been the subject of controversy since 2001, when it became the first biologic agent approved for the treatment of severe sepsis and septic shock. The PROWESS trial showed a 6.1 % absolute reduction in 28-day mortality, although these findings were not replicated in later trials, ultimately leading to the withdrawal of DAA in 2011. Observational trials, however, have consistently shown a mortality benefit with the use of DAA, leading to the following questions: Did DAA truly fail and, if so, why? While these questions may never be definitively answered on the basis of available evidence, several factors may explain the conflicting results. In clinical practice, DAA may have been preferentially given to subjects more likely to survive. Contemporary treatments, including early antibiotic administration and volume resuscitation, may have mitigated the inflammatory processes leading to disordered coagulation and microvascular thrombosis and, thus, reduced or abolished the therapeutic opportunity for DAA. Later randomized clinical trials of DAA focused on the clinical phenotype of refractory shock, largely due to a strong efficacy signal in this subset from PROWESS; however, this clinical phenotype may not be tightly linked, at least after contemporary early resuscitation strategies, to the mechanistic phenotype of dysregulated coagulation that may have been a better target for DAA. Future trials of biologic therapies in severe sepsis and septic shock should use a combination of clinical phenotype and biomarkers to identify responsive populations that may benefit from such therapies. C1 [Lai, Peggy S.; Thompson, B. Taylor] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Thompson, BT (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Bulfinch Suite 148,55 Fruit St, Boston, MA 02114 USA. EM tthompson1@partners.org OI Lai, Peggy/0000-0001-9501-8606 FU NHLBI FX Taylor Thompson has been a board member for Astra Zeneca; has been a consultant for Sirius Genetics, Immunetrics, and Lilly; and has received grant funding from NHLBI. NR 40 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3847 EI 1534-3146 J9 CURR INFECT DIS REP JI Curr. Infect. Dis. Rep. PD OCT PY 2013 VL 15 IS 5 BP 407 EP 412 DI 10.1007/s11908-013-0358-9 PG 6 WC Infectious Diseases SC Infectious Diseases GA AK2YT UT WOS:000338287200009 PM 23925482 ER PT J AU Jeon, HJ Hong, JP Fava, M Mischoulon, D Nyer, M Inamori, A Sohn, JH Seong, S Cho, MJ AF Jeon, Hong Jin Hong, Jin-Pyo Fava, Maurizio Mischoulon, David Nyer, Maren Inamori, Aya Sohn, Jee Hoon Seong, Sujeong Cho, Maeng Je TI Childhood parental death and lifetime suicide attempt of the opposite-gender offspring in a nationwide community sample of Korea SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Meeting Abstract C1 [Jeon, Hong Jin] Sungkyunkwan Univ, Depress Ctr, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Hong, Jin-Pyo] Univ Ulsan, Dept Psychiat, Asan Med Ctr, Coll Med, Seoul, South Korea. [Fava, Maurizio; Mischoulon, David; Nyer, Maren; Inamori, Aya] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. [Sohn, Jee Hoon; Seong, Sujeong; Cho, Maeng Je] Seoul Natl Univ, Coll Med, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1041-6102 EI 1741-203X J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PD OCT PY 2013 VL 25 SU 1 MA PS02-133 BP S180 EP S180 PG 1 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA AJ5UB UT WOS:000337753100409 ER PT J AU Sano, M Egelko, S Donohue, M Paparello, S Sun, CK Aisen, P Ferris, S Kaye, J Hayes, T Mundt, J AF Sano, Mary Egelko, Susan Donohue, Michael Paparello, Silvia Sun, Chung-Kai Aisen, Paul Ferris, Steven Kaye, Jeffrey Hayes, Tamara Mundt, James TI Satisfaction of elderly research participants with home-based clinical trial participation SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Meeting Abstract C1 [Sano, Mary; Egelko, Susan] Mt Sinai Sch Med, New York, NY USA. [Sano, Mary; Egelko, Susan] James J Peters VAMC, New York, NY USA. [Donohue, Michael; Paparello, Silvia; Sun, Chung-Kai; Aisen, Paul] Univ Calif San Diego, San Diego, CA 92103 USA. [Ferris, Steven] NYU Langone Med Ctr ADC, New York, NY USA. [Kaye, Jeffrey; Hayes, Tamara] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Mundt, James] Ctr Psychol Res Training & Consultat, Little Rock, AR USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1041-6102 EI 1741-203X J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PD OCT PY 2013 VL 25 SU 1 MA PS01-106 BP S109 EP S110 PG 2 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA AJ5UB UT WOS:000337753100247 ER PT J AU Shea, PL Spaeder, MC Sayal, P Jacobs, BR Stockwell, DC AF Shea, Paul L. Spaeder, Michael C. Sayal, Puneet Jacobs, Brian R. Stockwell, David C. TI Hypoglycemia Adverse Events in PICUs and Cardiac ICUs: Differentiating Preventable and Nonpreventable Events SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Article DE adverse events; hypoglycemia; insulin; patient safety; pediatrics; PICU; trigger ID CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; MEDICATION-RELATED HARM; FOCUSED TRIGGER TOOL; INSULIN THERAPY; NEONATAL HYPOGLYCEMIA; GLUCOSE VARIABILITY; INCREASED MORTALITY; DRUG EVENTS; CHILDREN AB Objectives: To describe the use of an adverse event detection system to identify, characterize, and categorize preventable versus nonpreventable hypoglycemia AEs in PICUs and cardiac ICUs. Design: Retrospective observational study. Setting: PICU and cardiac ICU of a tertiary pediatric hospital. Subjects: All hypoglycemia triggers generated over a 3-year period. Interventions: All hypoglycemia triggers generated via an electronic health record-driven surveillance system were investigated to determine if they represented a true adverse event and if that event was preventable or nonpreventable. Clinical and demographic variables were analyzed to identify characteristics of patients who developed a preventable or nonpreventable hypoglycemia adverse event. Measurements and Main Results: There were 197 hypoglycemia adverse events in 90 patients. Thirty percent of the adverse events in the PICU and 36% of the adverse events in the cardiac ICU were characterized as preventable. Of the adverse events, 118 (59.9%) necessitated an intravenous dextrose bolus. No adverse events were associated with reporting of symptoms of hypoglycemia including apnea, altered mental status, or seizures. Events were more likely to be preventable (p < 0.001) if the patient was receiving only parenteral sources of nutrition (intravenous fluids or total parenteral nutrition). Controlling for weekends and holidays, adverse events associated with sole parenteral nutrition source had an increased odds ratio of 9.5 (95% confidence interval: 2.8-31.9) of being preventable. Stratifying by ICU, cardiac ICU events occurring on a weekend or holiday were more likely to be preventable (p = 0.001). Stratifying by unit and controlling for parenteral nutrition source, adverse events in the cardiac ICU occurring on weekends or holidays had an increased odds ratio of 11.6 (95% confidence interval: 2.7-50.2) of being preventable. Conclusions: Preventable hypoglycemia adverse events are associated with patients receiving sole parenteral sources of nutrition in both the PICU and cardiac ICU. In the cardiac ICU, there is an association between weekend and holiday time periods and the development of preventable hypoglycemia adverse events. C1 [Shea, Paul L.] St Christophers Hosp Children, Dept Pediat, Sect Crit Care, Philadelphia, PA 19133 USA. [Shea, Paul L.] Drexel Univ, Coll Med, Dept Pediat, Philadelphia, PA 19104 USA. [Spaeder, Michael C.; Jacobs, Brian R.; Stockwell, David C.] Childrens Natl Med Ctr, Dept Crit Care Med, Washington, DC 20010 USA. [Spaeder, Michael C.; Jacobs, Brian R.; Stockwell, David C.] George Washington Univ, Sch Med, Dept Pediat, Washington, DC 20052 USA. [Sayal, Puneet] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Shea, PL (reprint author), St Christophers Hosp Children, Dept Pediat, Sect Crit Care, Philadelphia, PA 19133 USA. EM paul.shea@tenethealth.com FU Cerner Corporation, Kansas City, MO; Cerner Corporation FX Dr. Stockwell received a research grant from the Cerner Corporation, Kansas City, MO. Drs. Stockwell, Shea, Spaeder, Sayal, Jacobs, and Stockwell received funding from the Cerner Corporation. NR 37 TC 1 Z9 1 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1529-7535 EI 1947-3893 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD OCT PY 2013 VL 14 IS 8 BP 741 EP 746 DI 10.1097/PCC.0b013e3182975f0f PG 6 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA AI0EF UT WOS:000336518300007 PM 23863820 ER PT J AU Rajagopal, J Mou, HM AF Rajagopal, Jayaraj Mou, Hongmei TI IPS CELLS FOR CF AIRWAYS DISEASE SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract ID GFP-CFTR; DEGRADATION; MATURATION; EPITHELIUM C1 [Rajagopal, Jayaraj; Mou, Hongmei] Massachusetts Gen Hosp, Ctr Regenerat Pulmonol, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-6863 EI 1099-0496 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD OCT PY 2013 VL 48 SU 36 BP 106 EP 107 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA AF0FB UT WOS:000334387200006 ER PT J AU Vinarsky, V Chu, K Lam, A Wain, J Kim, JK Yun, SH Tearney, G Rajagopal, J AF Vinarsky, Vladimir Chu, Kengueh Lam, Adam Wain, John Kim, Jun Ki Yun, Seok-Hyun Tearney, Guillermo Rajagopal, Jayaraj TI HUMANIZED MICE FOR CF AIRWAYS RESEARCH SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract ID EPITHELIUM C1 [Vinarsky, Vladimir; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Vinarsky, Vladimir; Lam, Adam; Wain, John] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Chu, Kengueh; Kim, Jun Ki; Yun, Seok-Hyun; Tearney, Guillermo] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Rajagopal, Jayaraj] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-6863 EI 1099-0496 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD OCT PY 2013 VL 48 SU 36 BP 107 EP 109 PG 3 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA AF0FB UT WOS:000334387200007 ER PT J AU Madan, J Hibberd, PL AF Madan, Juliette Hibberd, Patricia L. TI THE GASTROINTESTINAL AND RESPIRATORY MICROBIOME IN CF: POTENTIAL INTERACTIONS SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract ID CYSTIC-FIBROSIS; GUT MICROBIOTA; RESPONSES; INFANTS; DISEASE C1 [Madan, Juliette] Dartmouth Hitchcock Med Ctr, Div Neonatol, Lebanon, NH 03766 USA. [Hibberd, Patricia L.] Massachusetts Gen Hosp, Dept Pediat, Div Global Hlth, Boston, MA 02114 USA. NR 19 TC 0 Z9 0 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-6863 EI 1099-0496 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD OCT PY 2013 VL 48 SU 36 BP 127 EP 128 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA AF0FB UT WOS:000334387200020 ER PT J AU Moskowitz, SM AF Moskowitz, Samuel M. TI COLISTIN RESISTANCE: AN EMERGING THREAT TO A LAST LINE THERAPY SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract ID CYSTIC-FIBROSIS PATIENTS; PSEUDOMONAS-AERUGINOSA; POLYMYXIN RESISTANCE; PEPTIDES; SYSTEM C1 [Moskowitz, Samuel M.] Massachusetts Gen Hosp, Cyst Fibrosis Ctr, Boston, MA 02114 USA. [Moskowitz, Samuel M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Moskowitz, Samuel M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-6863 EI 1099-0496 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD OCT PY 2013 VL 48 SU 36 BP 180 EP 181 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA AF0FB UT WOS:000334387200061 ER PT J AU Nippins, M AF Nippins, Matthew TI AIRWAY CLEARANCE AND PHYSICAL ACTIVITY: THE PERFECT HARMONY SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract ID CYSTIC-FIBROSIS; EXERCISE C1 [Nippins, Matthew] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-6863 EI 1099-0496 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD OCT PY 2013 VL 48 SU 36 BP 202 EP 203 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA AF0FB UT WOS:000334387200077 ER PT J AU Birket, S Chu, KK Li, Y Houser, GH Mazur, M Schuster, BS Hanes, J Tearney, GJ Rowe, SM AF Birket, S. Chu, K. K. Li, Y. Houser, G. H. Mazur, M. Schuster, B. S. Hanes, J. Tearney, G. J. Rowe, S. M. TI THE RELATIONSHIP BETWEEN PERICILIARY LIQUID HYDRATION AND MUCUS TRANSPORT IS AFFECTED BY BICARBONATE TRANSPORT SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Birket, S.; Li, Y.; Houser, G. H.; Mazur, M.; Rowe, S. M.] Univ Alabama Birmingham, Birmingham, AL USA. [Chu, K. K.; Tearney, G. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schuster, B. S.; Hanes, J.] Johns Hopkins, 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 8755-6863 EI 1099-0496 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD OCT PY 2013 VL 48 SU 36 BP 235 EP 236 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA AF0FB UT WOS:000334387200165 ER PT J AU Wilsterman, E Chu, KK Li, Y Diephuis, B Birket, S Schuster, BS Hanes, J Rowe, SM Tearney, GJ AF Wilsterman, E. Chu, K. K. Li, Y. Diephuis, B. Birket, S. Schuster, B. S. Hanes, J. Rowe, S. M. Tearney, G. J. TI RHEOLOGICAL VALIDATION OF PARTICLETRACKING MICRO-OPTICAL COHERENCE TOMOGRAPHY SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Wilsterman, E.; Chu, K. K.; Diephuis, B.; Tearney, G. J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Li, Y.; Birket, S.; Rowe, S. M.] Univ Alabama Birmingham, Birmingham, AL USA. [Schuster, B. S.; Hanes, J.] 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 8755-6863 EI 1099-0496 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD OCT PY 2013 VL 48 SU 36 BP 301 EP 302 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA AF0FB UT WOS:000334387200347 ER PT J AU Nick, JA Chmiel, J Forssen, A Hamblett, NM Moskowitz, SM Saiman, L Nichols, D AF Nick, J. A. Chmiel, J. Forssen, A. Hamblett, N. M. Moskowitz, S. M. Saiman, L. Nichols, D. TI AZITHROMYCIN APPEARS TO INHIBIT INHALED TOBRAMYCIN BUT NOT AZTREONAM WHEN TARGETING P-AERUGINOSA, IN THE CF AIRWAY SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Nick, J. A.; Forssen, A.; Nichols, D.] Natl Jewish Hlth, Denver, CO USA. [Chmiel, J.] Case Med Ctr, Cleveland, OH USA. [Hamblett, N. M.] Seattle Childrens Res Inst, TDN Coordinating Ctr, Seattle, WA USA. [Moskowitz, S. M.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Saiman, L.] Columbia Univ, Med Ctr, New York, NY 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 8755-6863 EI 1099-0496 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD OCT PY 2013 VL 48 SU 36 BP 305 EP 305 PG 1 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA AF0FB UT WOS:000334387200357 ER PT J AU Madan, J Li, J Koestler, D Moulton, L Hibberd, P Filkins, LM Morrison, H Guill, MF O'Toole, GA AF Madan, J. Li, J. Koestler, D. Moulton, L. Hibberd, P. Filkins, L. M. Morrison, H. Guill, M. F. O'Toole, G. A. TI THE DEVELOPING GUT AND RESPIRATORY TRACT MICROBIOME IN INFANTS WITH CF SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Madan, J.; Moulton, L.; Guill, M. F.] Dartmouth Hitchcock Med Ctr, Dept Pediat, Lebanon, NH 03766 USA. [Li, J.; Koestler, D.] Geisel Sch Med Dartmouth, Translat Genom Reserach Inst, Hanover, NH USA. [Filkins, L. M.; O'Toole, G. A.] Dartmouth Hitchcock Med Ctr, Dept Microbiol & Immunol, Lebanon, NH 03766 USA. [Morrison, H.] Marine Biol Lab, Josephine Bay Paul Ctr, Woods Hole, MA 02543 USA. [Hibberd, P.] Massachusetts Gen Hosp, Dept Pediat, Div Global Hlth, Boston, MA 02114 USA. RI Koestler, Devin /D-7902-2015 OI Koestler, Devin /0000-0002-0598-0146 NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-6863 EI 1099-0496 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD OCT PY 2013 VL 48 SU 36 BP 308 EP 309 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA AF0FB UT WOS:000334387200366 ER PT J AU Gutu, A Xavier, DE Sgambati, N Strasbourger, P Gales, AC Moskowitz, SM AF Gutu, A. Xavier, D. E. Sgambati, N. Strasbourger, P. Gales, A. C. Moskowitz, S. M. TI ENHANCED POLYMYXIN RESISTANCE OF PSEUDOMONAS AERUGINOSA ASSOCIATED WITH MUTATIONS IN A PHOSPHATE TRANSPORT SYSTEM SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Gutu, A.; Sgambati, N.; Moskowitz, S. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Xavier, D. E.; Gales, A. C.] Univ Fed Sao Paulo, Div Infect Dis, Lab Alerta, Sao Paulo, Brazil. [Strasbourger, P.] Univ Washington, Seattle, WA 98195 USA. [Moskowitz, S. M.] Harvard Univ, Sch Med, Boston, MA USA. RI Gales, Ana/C-8280-2013 OI Gales, Ana/0000-0003-0913-768X 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 8755-6863 EI 1099-0496 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD OCT PY 2013 VL 48 SU 36 BP 309 EP 309 PG 1 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA AF0FB UT WOS:000334387200368 ER PT J AU Havasi, V Clines, GA Stalvey, MS AF Havasi, V Clines, G. A. Stalvey, M. S. TI REDUCED BONE DENSITY IN G551D-CFTR MICE: A NOVEL MODEL TO STUDY EFFECTS OF CFTR ON BONE METABOLISM SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Havasi, V; Clines, G. A.; Stalvey, M. S.] Univ Alabama Birmingham, Birmingham, AL USA. [Clines, G. A.] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL 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 8755-6863 EI 1099-0496 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD OCT PY 2013 VL 48 SU 36 BP 419 EP 420 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA AF0FB UT WOS:000334387200658 ER PT J AU Tennis, P Johannes, C Camargo, CA Sturmer, T Lanes, S Brown, J Andrews, E Davis, K Schatz, M AF Tennis, Patricia Johannes, Catherine Camargo, C. A., Jr. Stuermer, Til Lanes, Stephan Brown, Jeff Andrews, Elizabeth Davis, Kourtney Schatz, Michael TI Feasibility of Ruling out Small Treatment-Associated Increase in Asthma Mortality Risk SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Tennis, Patricia; Johannes, Catherine; Andrews, Elizabeth] RTI Hlth Solut, Res Triangle Pk, NC USA. [Camargo, C. A., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stuermer, Til] Univ N Carolina, Chapel Hill, NC USA. [Lanes, Stephan] United BioSource Corp, Lexington, MA USA. [Brown, Jeff] Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Davis, Kourtney] GlaxoSmithKline R&D, Res Triangle Pk, NC USA. [Schatz, Michael] So Calif Permanente Med Grp, San Diego, CA 92120 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2013 VL 22 SU 1 SI SI MA 64 BP 34 EP 35 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AF7EJ UT WOS:000334876100065 ER PT J AU Bateman, BT Bykov, K Schneeweiss, S Gagne, J Polinski, JM Franklin, JM Fischer, MA Choudhry, NK Rassen, JA AF Bateman, Brian T. Bykov, Katsiaryna Schneeweiss, Sebastian Gagne, Joshua Polinski, Jennifer M. Franklin, Jessica M. Fischer, Michael A. Choudhry, Niteesh K. Rassen, Jeremy A. TI Type of Stress Ulcer Prophylaxis and the Risk of Nosocomial Pneumonia in Cardiac Surgical Patients SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Bateman, Brian T.; Bykov, Katsiaryna; Schneeweiss, Sebastian; Gagne, Joshua; Polinski, Jennifer M.; Franklin, Jessica M.; Fischer, Michael A.; Choudhry, Niteesh K.; Rassen, Jeremy A.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Bateman, Brian T.; Bykov, Katsiaryna; Schneeweiss, Sebastian; Gagne, Joshua; Polinski, Jennifer M.; Franklin, Jessica M.; Fischer, Michael A.; Choudhry, Niteesh K.; Rassen, Jeremy A.] Harvard Univ, Sch Med, Boston, MA USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RI Schneeweiss, Sebastian/C-2125-2013 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2013 VL 22 SU 1 SI SI MA 66 BP 35 EP 36 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AF7EJ UT WOS:000334876100067 ER PT J AU Soriano, LC Bateman, BT Rodriguez, LAG Hernandez-Diaz, S AF Cea Soriano, Lucia Bateman, Brian T. Garcia Rodriguez, Luis A. Hernandez-Diaz, Sonia TI Hypertension and Patterns of Prescription of Antihypertensive Medications during Pregnancy Using THIN Database SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Cea Soriano, Lucia; Garcia Rodriguez, Luis A.] Spanish Ctr Pharmacoepidemiol Res CEIFE, Madrid, Spain. [Cea Soriano, Lucia; Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Bateman, Brian T.] Harvard Univ, Div Pharmacoepidemiol & Pharmacoecon, Dept Anesthesia Crit Care & Pain Med,Sch Med, Brigham & Womens Hosp,Massachusetts Gen Hosp, Boston, MA 02115 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2013 VL 22 SU 1 SI SI MA 301 BP 145 EP 146 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AF7EJ UT WOS:000334876100280 ER PT J AU Bateman, BT Huybrechts, KF Hernandez-Diaz, S Liu, J Avorn, J AF Bateman, Brian T. Huybrechts, Krista F. Hernandez-Diaz, Sonia Liu, Jun Avorn, Jerry TI Methylergonovine Maleate and the Risk of Myocardial Ischemia and Infarction SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Bateman, Brian T.; Huybrechts, Krista F.; Liu, Jun; Avorn, Jerry] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Bateman, Brian T.; Huybrechts, Krista F.; Liu, Jun; Avorn, Jerry] Harvard Univ, Sch Med, Boston, MA USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2013 VL 22 SU 1 SI SI MA 399 BP 195 EP 195 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AF7EJ UT WOS:000334876100376 ER PT J AU Yenikomshian, MA LaCasce, AS Skarin, AT Trahey, A Guignard, A Haguinet, FF Karner, PE Duh, MS AF Yenikomshian, Mihran A. LaCasce, Ann S. Skarin, Arthur T. Trahey, Alex Guignard, Adrienne Haguinet, Francois F. Karner, Paul E. Duh, Mei S. TI The Epidemiology of Herpes Zoster (HZ) and Its Complications in Medicare Cancer Patients SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Yenikomshian, Mihran A.; Trahey, Alex; Karner, Paul E.; Duh, Mei S.] Anal Grp, Boston, MA USA. [LaCasce, Ann S.; Skarin, Arthur T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Guignard, Adrienne; Haguinet, Francois F.] GlaxoSmithKline Biol, Wavre, Belgium. 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2013 VL 22 SU 1 SI SI MA 551 BP 271 EP 271 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AF7EJ UT WOS:000334876101119 ER PT J AU Johannes, CB McQuay, LJ Tennis, P Camargo, CA Schatz, M Midkiff, KD Lanes, S DiSantostefano, R Davis, KJ AF Johannes, Catherine B. McQuay, Lisa J. Tennis, Patricia Camargo, Carlos A., Jr. Schatz, Michael Midkiff, Kirk D. Lanes, Stephan DiSantostefano, Rachael Davis, Kourtney J. TI Characteristics of Initiators of Asthma Maintenance Medications in 10 Health Care Populations SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Johannes, Catherine B.] RTI Hlth Solut, Epidemiol, Waltham, MA USA. [McQuay, Lisa J.; Tennis, Patricia; Midkiff, Kirk D.] RTI Hlth Solut, Epidemiol, Res Triangle Pk, NC USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schatz, Michael] So Calif Permanente Med Grp, San Diego, CA 92120 USA. [Lanes, Stephan] United BioSource Corp, Lexington, MA USA. [DiSantostefano, Rachael; Davis, Kourtney J.] GlaxoSmithKline R&D, Res Triangle Pk, NC 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2013 VL 22 SU 1 SI SI MA 555 BP 273 EP 274 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AF7EJ UT WOS:000334876101123 ER PT J AU Linsky, A Simon, SR Bokhour, B AF Linsky, Amy Simon, Steven R. Bokhour, Barbara TI Clinical Provider Perceptions of Intentional Medication Discontinuation SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Linsky, Amy; Simon, Steven R.] VA Boston Healthcare Syst, Gen Internal Med, Boston, MA USA. [Linsky, Amy; Simon, Steven R.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Linsky, Amy; Simon, Steven R.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Linsky, Amy; Simon, Steven R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bokhour, Barbara] ENRM Vet Affairs Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Bokhour, Barbara] Boston Univ, Sch Publ Hlth, Boston, MA 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2013 VL 22 SU 1 SI SI MA 911 BP 456 EP 457 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AF7EJ UT WOS:000334876102029 ER PT J AU Linsky, A Volk, L Maniam, N Simon, SR AF Linsky, Amy Volk, Lynn Maniam, Nivethietha Simon, Steven R. TI Effect of Computerized Clinical Decision Support on Appropriate Laboratory Monitoring of Medications SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Linsky, Amy; Simon, Steven R.] VA Boston Healthcare Syst, Gen Internal Med, Boston, MA USA. [Linsky, Amy; Simon, Steven R.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Linsky, Amy; Simon, Steven R.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Linsky, Amy; Simon, Steven R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Volk, Lynn; Maniam, Nivethietha] Partners Healthcare Syst, Boston, MA 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2013 VL 22 SU 1 SI SI MA 960 BP 480 EP 481 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AF7EJ UT WOS:000334876102072 ER PT J AU Munoz, JL Bliss, SA Greco, SJ Ramkissoon, SH Ligon, KL Rameshwar, P AF Munoz, Jessian L. Bliss, Sarah A. Greco, Steven J. Ramkissoon, Shakti H. Ligon, Keith L. Rameshwar, Pranela TI Delivery of Functional Anti-miR-9 by Mesenchymal Stem Cell-derived Exosomes to Glioblastoma Multiforme Cells Conferred Chemosensitivity SO MOLECULAR THERAPY-NUCLEIC ACIDS LA English DT Article ID BREAST-CANCER; GLIOMA; CHEMORESISTANCE; ACTIVATION; EXPRESSION; MICRORNAS; ABCB1 AB Glioblastoma multiforme (GBM), the most common and lethal tumor of the adult brain, generally shows chemo-and radioresistance. MicroRNAs (miRs) regulate physiological processes, such as resistance of GBM cells to temozolomide (TMZ). Although miRs are attractive targets for cancer therapeutics, the effectiveness of this approach requires targeted delivery. Mesenchymal stem cells (MSCs) can migrate to the sites of cancers, including GBM. We report on an increase in miR-9 in TMZ-resistant GBM cells. miR-9 was involved in the expression of the drug efflux transporter, P-glycoprotein. To block miR-9, methods were developed with Cy5-tagged anti-miR-9. Dye-transfer studies indicated intracellular communication between GBM cells and MSCs. This occurred by gap junctional intercellular communication and the release of microvesicles. In both cases, anti-miR-9 was transferred from MSCs to GBM cells. However, the major form of transfer occurred with the microvesicles. The delivery of anti-miR-9 to the resistant GBM cells reversed the expression of the multidrug transporter and sensitized the GBM cells to TMZ, as shown by increased cell death and caspase activity. The data showed a potential role for MSCs in the functional delivery of synthetic anti-miR-9 to reverse the chemoresistance of GBM cells. C1 [Munoz, Jessian L.; Bliss, Sarah A.] Rutgers State Univ, Sch Biomed Sci, Newark, NJ 07102 USA. [Munoz, Jessian L.; Bliss, Sarah A.; Greco, Steven J.; Rameshwar, Pranela] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. [Ramkissoon, Shakti H.; Ligon, Keith L.] Boston Childrens Hosp, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. [Ramkissoon, Shakti H.; Ligon, Keith L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Rameshwar, P (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Rutgers Biomed Hlth Sci, 185 South Orange Ave,MSB E-585, Newark, NJ 07103 USA. EM rameshwa@njms.rutgers.edu NR 27 TC 70 Z9 74 U1 6 U2 24 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2162-2531 J9 MOL THER-NUCL ACIDS JI Mol. Ther.-Nucl. Acids PD OCT PY 2013 VL 2 AR e126 DI 10.1038/mtna.2013.60 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AC4CQ UT WOS:000332468600002 PM 24084846 ER PT J AU Roetker, NS Page, CD Yonker, JA Chang, V Roan, CL Herd, P Hauser, TS Hauser, RM Atwood, CS AF Roetker, Nicholas S. Page, C. David Yonker, James A. Chang, Vicky Roan, Carol L. Herd, Pamela Hauser, Taissa S. Hauser, Robert M. Atwood, Craig S. TI Assessment of Genetic and Nongenetic Interactions for the Prediction of Depressive Symptomatology: An Analysis of the Wisconsin Longitudinal Study Using Machine Learning Algorithms SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID NATIONAL COMORBIDITY SURVEY; SEROTONIN TRANSPORTER GENE; GENOME-WIDE ASSOCIATION; STRESSFUL LIFE EVENTS; HORMONE-RECEPTOR GENE; MAJOR DEPRESSION; ADULT DEPRESSION; ENVIRONMENT INTERACTIONS; CHILDHOOD MALTREATMENT; TREATMENT RESPONSE AB Objectives. We examined depression within a multidimensional framework consisting of genetic, environmental, and sociobehavioral factors and, using machine learning algorithms, explored interactions among these factors that might better explain the etiology of depressive symptoms. Methods. We measured current depressive symptoms using the Center for Epidemiologic Studies Depression Scale (n = 6378 participants in the Wisconsin Longitudinal Study). Genetic factors were 78 single nucleotide polymorphisms (SNPs); environmental factors-13 stressful life events (SLEs), plus a composite proportion of SLEs index; and sociobehavioral factors-18 personality, intelligence, and other health or behavioral measures. We performed traditional SNP associations via logistic regression likelihood ratio testing and explored interactions with support vector machines and Bayesian networks. Results. After correction for multiple testing, we found no significant single genotypic associations with depressive symptoms. Machine learning algorithms showed no evidence of interactions. Naive Bayes produced the best models in both subsets and included only environmental and sociobehavioral factors. Conclusions. We found no single or interactive associations with genetic factors and depressive symptoms. Various environmental and sociobehavioral factors were more predictive of depressive symptoms, yet their impacts were independent of one another. A genome-wide analysis of genetic alterations using machine learning methodologies will provide a framework for identifying genetic-environmental-sociobehavioral interactions in depressive symptoms. C1 [Roetker, Nicholas S.; Yonker, James A.; Chang, Vicky; Roan, Carol L.; Herd, Pamela; Hauser, Taissa S.; Hauser, Robert M.] Univ Wisconsin Madison, Dept Sociol, Madison, WI 53715 USA. [Herd, Pamela] Univ Wisconsin Madison, La Follete Sch Publ Affairs, Madison, WI USA. [Page, C. David] Univ Wisconsin Madison, Dept Biostat & Med Informat, Madison, WI USA. [Atwood, Craig S.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Atwood, Craig S.] Univ Wisconsin Madison Sch Med & Publ Hlth, Dept Med, Madison, WI 53705 USA. RP Atwood, CS (reprint author), Univ Wisconsin Madison Sch Med & Publ Hlth, William S Middleton Mem Vet Hosp GRECC 11G, 2500 Overlook Terrace, Madison, WI 53705 USA. EM csa@medicine.wisc.edu RI Yonker, James/J-6561-2014 OI Yonker, James/0000-0002-9483-8511 FU National Institute on Aging [AG-9775, AG-21079, AG-033285]; Vilas Estate Trust; National Science Foundation; Spencer Foundation; Graduate School of the University of Wisconsin-Madison FX This research used data from the Wisconsin Longitudinal Study (WLS) of the University of Wisconsin-Madison. Since 1991, the WLS has been supported principally by the National Institute on Aging (AG-9775, AG-21079, and AG-033285), with additional support from the Vilas Estate Trust, the National Science Foundation, the Spencer Foundation, and the Graduate School of the University of Wisconsin-Madison. A public use file of data from the Wisconsin Longitudinal Study is available from the WLS, University of Wisconsin-Madison, 1180 Observatory Drive, Madison, WI 53706, and at http://www.ssc.wisc.edu/wlsresearch/data. This material is the result of work supported with resources at the William S. Middleton Memorial Veterans Hospital, Madison, WI. NR 82 TC 1 Z9 1 U1 2 U2 9 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2013 VL 103 SU 1 BP 136 EP 144 DI 10.2105/AJPH.2012.301141 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA4NC UT WOS:000331071600021 ER PT J AU Shea, S Kothari, D Teresi, JA Kong, J Eimicke, JP Lantigua, RA Palmas, W Weinstock, RS AF Shea, Steven Kothari, Dhruva Teresi, Jeanne A. Kong, Jian Eimicke, Joseph P. Lantigua, Rafael A. Palmas, Walter Weinstock, Ruth S. TI Social Impact Analysis of the Effects of a Telemedicine Intervention to Improve Diabetes Outcomes in an Ethnically Diverse, Medically Underserved Population: Findings From the IDEATel Study SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID COLUMBIA-UNIVERSITY INFORMATICS; RANDOMIZED CONTROLLED-TRIALS; BLOOD-PRESSURE; CARE; EDUCATION; MODEL; CHOLESTEROL; MANAGEMENT; MELLITUS; PROJECT AB Objectives. We examined the social impact of the telemedicine intervention effects in lower-and higher-socioeconomic status (SES) participants in the Informatics for Diabetes Education and Telemedicine (IDEATel) study. Methods. We conducted a randomized controlled trial comparing telemedicine case management with usual care, with blinded outcome evaluation, in 1665 Medicare recipients with diabetes, aged 55 years or older, residing in federally designated medically underserved areas of New York State. The primary trial endpoints were hemoglobin A1c (HbA1c), low-density lipoprotein cholesterol, and systolic blood pressure levels. Results. HbA1c was higher in lower-income participants at the baseline examination. However, we found no evidence that the intervention increased disparities. A significant moderator effect was seen for HbA1c (P = .004) and systolic blood pressure (P = .023), with the lowest-income group showing greater intervention effects. Conclusions. Lower-SES participants in the IDEATel study benefited at least as much as higher-SES participants from telemedicine nurse case management for diabetes. Tailoring the intensity of the intervention based on clinical need may have led to greater improvements among those not at goal for diabetes control, a group that also had lower income, thereby avoiding the potential for an innovative intervention to widen socioeconomic disparities. C1 [Shea, Steven; Lantigua, Rafael A.; Palmas, Walter] Columbia Univ, Dept Med, New York, NY USA. [Kothari, Dhruva] Columbia Univ Coll Phys & Surg, New York, NY USA. [Teresi, Jeanne A.; Kong, Jian; Eimicke, Joseph P.] Hebrew Home Riverdale, Div Res, Bronx, NY USA. [Teresi, Jeanne A.] Columbia Univ, Morris W Stroud III Ctr Studies Qual Life, New York, NY USA. [Weinstock, Ruth S.] SUNY Upstate Med Univ, Joslin Diabet Ctr, Syracuse, NY 13210 USA. [Weinstock, Ruth S.] SUNY Upstate Med Univ, Div Endocrinol Diabet & Metab, Syracuse, NY 13210 USA. RP Shea, S (reprint author), Div Gen Med, 630 W 168th St, New York, NY 10032 USA. EM ss35@columbia.edu FU Centers for Medicare and Medicaid Services [95-C-90998]; National Institute on Minority Health and Health Disparities [P60-MD000206] FX This project was supported by the Centers for Medicare and Medicaid Services (cooperative agreement 95-C-90998) and by the National Institute on Minority Health and Health Disparities (grant P60-MD000206). NR 25 TC 6 Z9 6 U1 0 U2 9 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2013 VL 103 IS 10 BP 1888 EP 1894 DI 10.2105/AJPH.2012.300909 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA3PK UT WOS:000331004600045 PM 23488491 ER PT J AU Blosnich, JR Brown, GR Shipherd, JC Kauth, M Piegari, RI Bossarte, RM AF Blosnich, John R. Brown, George R. Shipherd, Jillian C. Kauth, Michael Piegari, Rebecca I. Bossarte, Robert M. TI Prevalence of Gender Identity Disorder and Suicide Risk Among Transgender Veterans Utilizing Veterans Health Administration Care SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CROSS-SEX HORMONES; TRANSSEXUALISM; IDEATION; BEHAVIORS; MORTALITY AB Objectives. We estimated the prevalence and incidence of gender identity disorder (GID) diagnoses among veterans in the Veterans Health Administration (VHA) health care system and examined suicide risk among veterans with a GID diagnosis. Methods. We examined VHA electronic medical records from 2000 through 2011 for 2 official ICD-9 diagnosis codes that indicate transgender status. We generated annual period prevalence estimates and calculated incidence using the prevalence of GID at 2000 as the baseline year. We cross-referenced GID cases with available data (2009-2011) of suicide-related events among all VHA users to examine suicide risk. Results. GID prevalence in the VHA is higher (22.9/100 000 persons) than are previous estimates of GID in the general US population (4.3/100 000 persons). The rate of suicide-related events among GID-diagnosed VHA veterans was more than 20 times higher than were rates for the general VHA population. Conclusions. The prevalence of GID diagnosis nearly doubled over 10 years among VHA veterans. Research is needed to examine suicide risk among transgender veterans and how their VHA utilization may be enhanced by new VA initiatives on transgender care. C1 [Blosnich, John R.] Univ Rochester, Dept Psychiat, Rochester, NY USA. [Brown, George R.] VA Off Hlth Equ 10A6, Washington, DC USA. [Shipherd, Jillian C.] VA Boston Healthcare Syst, Boston, MA USA. [Kauth, Michael] Michael E DeBakey VA Med Ctr, Educ & Clin Ctr, VA South Cent Mental Illness Res, Houston, TX USA. [Piegari, Rebecca I.; Bossarte, Robert M.] Ctr Excellence Suicide Prevent, Dept Vet Affairs VISN 2, Canandaigua, NY 14424 USA. RP Blosnich, JR (reprint author), Ctr Excellence Suicide Prevent, Dept Vet Affairs VISN 2, 400 Ft Hill Ave, Canandaigua, NY 14424 USA. EM john_blosnich@urmc.rochester.edu FU Department of Veterans Affairs VISN-2 Center of Excellence for Suicide Prevention; National Institute of Mental Health [5T32MH02006112] FX This work was partially supported by the Department of Veterans Affairs VISN-2 Center of Excellence for Suicide Prevention and by a postdoctoral fellowship in an Institutional National Research Service Award from the National Institute of Mental Health (award 5T32MH02006112 to J.R.B.). NR 47 TC 43 Z9 43 U1 0 U2 16 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2013 VL 103 IS 10 BP E27 EP E32 DI 10.2105/AJPH.2013.301507 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA3PK UT WOS:000331004600013 PM 23947310 ER PT J AU Hirsch, JA Donovan, WD Nicola, GN Barr, RM Schaefer, PW Silva, E AF Hirsch, J. A. Donovan, W. D. Nicola, G. N. Barr, R. M. Schaefer, P. W. Silva, E., III TI Alphabet Soup: Our Government "In-Action" SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Editorial Material ID RUC C1 [Hirsch, J. A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Program, Boston, MA 02114 USA. [Donovan, W. D.] Norwich Diagnost Imaging Associates, Norwich, CT USA. [Nicola, G. N.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Barr, R. M.] Mecklenburg Radiol Associates, Charlotte, NC USA. [Schaefer, P. W.] Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. [Silva, E., III] Univ Texas San Antonio, South Texas Radiol Grp, San Antonio, TX USA. RP Hirsch, JA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroendovasc Program, Boston, MA 02114 USA. EM Hirsch@snisonline.org OI Barr, Robert/0000-0002-9214-9448 NR 13 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD OCT PY 2013 VL 34 IS 10 BP 1887 EP 1889 DI 10.3174/ajnr.A3672 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 301NQ UT WOS:000330539400008 PM 23811971 ER PT J AU Barakos, J Sperling, R Salloway, S Jack, C Gass, A Fiebach, JB Tampieri, D Melancon, D Miaux, Y Rippon, G Black, R Lu, Y Brashear, HR Arrighi, HM Morris, KA Grundman, M AF Barakos, J. Sperling, R. Salloway, S. Jack, C. Gass, A. Fiebach, J. B. Tampieri, D. Melancon, D. Miaux, Y. Rippon, G. Black, R. Lu, Y. Brashear, H. R. Arrighi, H. M. Morris, K. A. Grundman, M. TI MR Imaging Features of Amyloid-Related Imaging Abnormalities SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID ANGIOPATHY-RELATED INFLAMMATION; ALZHEIMERS-DISEASE; BRAIN; BETA; BAPINEUZUMAB; TRIALS AB BACKGROUND AND PURPOSE: AD is one of the few leading causes of death without a disease-modifying drug; however, hopeful agents are in various phases of development. MR imaging abnormalities, collectively referred to as amyloid-related imaging abnormalities, have been reported for several agents that target cerebral A beta burden. ARIA includes ARIA-E, parenchymal or sulcal hyperintensities on FLAIR indicative of parenchymal edema or sulcal effusions, and ARIA-H, hypointense regions on gradient recalled-echo/T2* indicative of hemosiderin deposition. This report describes imaging characteristics of ARIA-E and ARIA-H identified during studies of bapineuzumab, a humanized monoclonal antibody against A beta. MATERIALS AND METHODS: Two neuroradiologists with knowledge of imaging changes reflective of ARIA reviewed MR imaging scans from 210 bapineuzumab-treated patients derived from 3 phase 2 studies. Each central reader interpreted the studies independently, and discrepancies were resolved by consensus. The inter-reader kappa was 0.76, with 94% agreement between neuroradiologists regarding the presence or absence of ARIA-E in individual patients. RESULTS: Thirty-six patients were identified with incident ARIA-E (17.1%, 36/210) and 26 with incident ARIA-H (12.4%, 26/210); of those with incident ARIA-H, 24 had incident microhemorrhages and 2 had incident large superficial hemosiderin deposits. CONCLUSIONS: In 49% of cases of ARIA-E, there was the associated appearance of ARIA-H. In treated patients without ARIA-E, the risk for incident blood products was 4%. This association between ARIA-E and ARIA-H may suggest a common pathophysiologic mechanism. Familiarity with ARIA should permit radiologists and clinicians to recognize and communicate ARIA findings more reliably for optimal patient management. C1 [Barakos, J.] Calif Pacific Med Ctr, San Francisco, CA 94115 USA. [Barakos, J.; Miaux, Y.] Synarc, Newark, CA USA. [Sperling, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Brigham & Womens Hosp, Boston, MA USA. [Salloway, S.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Jack, C.] Mayo Clin, Rochester, MN USA. [Gass, A.] Heidelberg Univ, Univ Hosp Mannheim, Mannheim, Germany. [Fiebach, J. B.] Charite, Ctr Stroke Res, Berlin, Germany. [Tampieri, D.; Melancon, D.] NeuroRx Res, Montreal, PQ, Canada. [Rippon, G.; Black, R.] Pfizer Inc, Collegeville, PA USA. [Brashear, H. R.; Arrighi, H. M.; Morris, K. A.; Grundman, M.] Janssen Alzheimer Immunotherapy Res & Dev LLC, San Francisco, CA USA. [Grundman, M.] Global Partners Inc, Cambridge, MA USA. RP Barakos, J (reprint author), Calif Pacific Med Ctr, 2333 Buchanan St, San Francisco, CA 94115 USA. EM barakosmd@gmail.com RI Jack, Clifford/F-2508-2010; OI Jack, Clifford/0000-0001-7916-622X; Fiebach, Jochen B./0000-0002-7936-6958 FU Janssen Alzheimer Immunotherapy Research & Development, LLC; Pfizer Inc.; Pfizer Inc; Janssen Alzheimer Immunotherapy Research & Development, LLC. FX This work was supported by Janssen Alzheimer Immunotherapy Research & Development, LLC, and Pfizer Inc. Michael Grundman was a paid consultant to Janssen Alzheimer Immunotherapy Research & Development, LLC, in the development of this article. Editorial support was provided by Lisette T. Arnaud, PhD, at Phase Five Communications Inc and was funded by Pfizer Inc and Janssen Alzheimer Immunotherapy Research & Development, LLC. NR 21 TC 10 Z9 10 U1 1 U2 5 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD OCT PY 2013 VL 34 IS 10 BP 1958 EP 1965 DI 10.3174/ajnr.A3500 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 301NQ UT WOS:000330539400020 PM 23578674 ER PT J AU Leslie-Mazwi, TM Heddier, M Nordmeyer, H Stauder, M Velasco, A Mosimann, PJ Chapot, R AF Leslie-Mazwi, T. M. Heddier, M. Nordmeyer, H. Stauder, M. Velasco, A. Mosimann, P. J. Chapot, R. TI Stent Retriever Use for Retrieval of Displaced Microcoils: A Consecutive Case Series SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID GUGLIELMI DETACHABLE COILS; ANEURYSMS AB Coil displacement during endovascular coiling procedures may require coil retrieval in the context of flow limitation or thromboembolic risk. No standard recommended method of coil retrieval exists. We present a consecutive series of 14 patients with displaced coil during aneurysm coiling in whom the complication was effectively managed with the use of a stent retriever system. Two illustrative cases from the 14 are described, and technical notes are detailed regarding use of the technique. The use of stent retrievers presents a simple, safe, and effective choice for removal of prolapsed coils during aneurysm coiling. C1 [Leslie-Mazwi, T. M.; Heddier, M.; Nordmeyer, H.; Stauder, M.; Velasco, A.; Mosimann, P. J.; Chapot, R.] Alfried Krupp Hosp, Dept Intervent Neuroradiol, Essen, Germany. [Leslie-Mazwi, T. M.] Massachusetts Gen Hosp, Dept Intervent Neuroradiol Endovasc Neurosurg, Boston, MA 02114 USA. [Mosimann, P. J.] CHU Vaudois, Dept Radiol & Neuroradiol, CH-1011 Lausanne, Switzerland. Univ Lausanne, Lausanne, Switzerland. RP Chapot, R (reprint author), Dept Intracranial Endovasc Therapy, Alfried Krupp Str 21, D-45131 Essen, Germany. EM rene.chapot@krupp-krankenhaus.de NR 15 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD OCT PY 2013 VL 34 IS 10 BP 1996 EP 1999 DI 10.3174/ajnr.A3552 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 301NQ UT WOS:000330539400027 PM 23764724 ER PT J AU Elmi, A Hedgire, SS Covarrubias, D Abtahi, SM Hahn, PF Harisinghani, M AF Elmi, A. Hedgire, S. S. Covarrubias, D. Abtahi, S. M. Hahn, P. F. Harisinghani, M. TI Apparent diffusion coefficient as a non-invasive predictor of treatment response and recurrence in locally advanced rectal cancer SO CLINICAL RADIOLOGY LA English DT Article ID WEIGHTED MRI; RADIOTHERAPY; CHEMORADIATION; MANAGEMENT; THERAPY; VALUES AB AIM: To evaluate the role of pretreatment apparent diffusion coefficient (ADC) as a predictor of treatment response and local recurrence in patients with locally advanced rectal cancer who underwent neoadjuvant therapy. MATERIALS AND METHODS: Forty-nine patients who underwent preoperative diffusion-weighted magnetic resonance imaging (MRI) followed by neoadjuvant chemoradiation and surgery were enrolled in the study. The mean tumour ADC was measured independently from multiple, non-overlapping regions of interest (ROIs) to cover the entire tumour area on a single section by two radiologists and patients were followed postoperatively for a median of 16.4 months. Diagnostic accuracy of ADC for predicting treatment response and recurrence was evaluated using the area under the receiver-operating characteristic (ROC) curve, sensitivity, specificity, and predictive values. Univariate and multivariate analyses including clinical tumour (cT) staging, carcinoembryonic antigen (CEA) level, lymph-node involvement, tumour grade, surgical margin, vascular involvement, and ADC were performed with respect to recurrence. Interobserver agreement of ADC values was assessed. RESULTS: Twenty patients showed response to neoadjuvant therapy and recurrence was noted in 17 patients. Low pretreatment ADC, MRI findings of cT4 staging, and node involvement were significantly related to poor treatment response. Sensitivity and specificity of ADC = 0.833 x 10(-3) mm(2)/s for prediction of treatment response was 75 and 48% for reader 1 and 65 and 52% for reader 2, respectively. Univariate and multivariate analyses identified pretreatment tumour ADC as the only predictive factor for recurrence. Sensitivity and specificity of ADC = 0.833 x 10(-3) mm(2)/s for prediction of recurrence was 86 and 77% for reader 1 and 80 and 69% for reader 2, respectively. Interobserver agreement for measuring ADC was good with a kappa value of 0.70. CONCLUSION: Pretreatment rectal tumour ADC values may be an early biomarker for predicting treatment response and local recurrence in patients who underwent neoadjuvant chemoradiation. (C) 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. C1 [Elmi, A.; Hedgire, S. S.; Covarrubias, D.; Abtahi, S. M.; Hahn, P. F.; Harisinghani, M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA USA. RP Elmi, A (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM aelmi@partners.org NR 26 TC 19 Z9 19 U1 0 U2 9 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0009-9260 EI 1365-229X J9 CLIN RADIOL JI Clin. Radiol. PD OCT PY 2013 VL 68 IS 10 BP E524 EP E531 DI 10.1016/j.crad.2013.05.094 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AA5UV UT WOS:000331166000002 PM 23830776 ER PT J AU Ioannou, GN Scott, JD Yang, Y Green, P Beste, LA AF Ioannou, George N. Scott, John D. Yang, Yin Green, Pamela Beste, Lauren A. TI Antiviral Treatment for Hepatitis C Virus in HIV/HCV Co-infected Patients SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Ioannou, George N.; Yang, Yin; Green, Pamela; Beste, Lauren A.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Ioannou, George N.; Scott, John D.] Univ Washington, Seattle, WA 98195 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 37 BP 225A EP 225A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252201037 ER PT J AU Patel, SJ Luther, J King, KR Bohr, S Scichilone, J Garber, J Peng, LF Chung, RT Yarmush, ML AF Patel, Suraj J. Luther, Jay King, Kevin R. Bohr, Stefan Scichilone, John Garber, John Peng, Lee F. Chung, Raymond T. Yarmush, Martin L. TI Hepatic Gap Junction Inhibition Limits Liver Injury and Inflammation in Non-alcoholic Steatohepatitis (NASH) SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Patel, Suraj J.; Luther, Jay; King, Kevin R.; Bohr, Stefan; Scichilone, John; Garber, John; Peng, Lee F.; Chung, Raymond T.; Yarmush, Martin L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Patel, Suraj J.; Bohr, Stefan; Scichilone, John; Yarmush, Martin L.] Shriners Burns Hosp, 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 50 BP 232A EP 232A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252201050 ER PT J AU Hammond, SP Ho, VT Ukomadu, C Baden, LR Marty, FM AF Hammond, Sarah P. Ho, Vincent T. Ukomadu, Chinweike Baden, Lindsey R. Marty, Francisco M. TI Hepatitis B Virus (HBV) Reverse Seroconversion after Allogeneic Hematopoietic Stem Cell Transplantation the Impact of Post-Transplant Vaccination SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Hammond, Sarah P.; Baden, Lindsey R.; Marty, Francisco M.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Hammond, Sarah P.; Ho, Vincent T.; Baden, Lindsey R.; Marty, Francisco M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ukomadu, Chinweike] Brigham & Womens Hosp, Div Gastroenterol, 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 192 BP 303A EP 304A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252201192 ER PT J AU Zhu, CL Hong, J Zhao, L Chusri, P Jilg, N Fusco, DN Schaefer, EA Brisac, C Chevaliez, S Wambua, D Peng, LF Lin, WY Chung, RT AF Zhu, Chuanlong Hong, Jian Zhao, Lei Chusri, Pattranuch Jilg, Nikolaus Fusco, Dahlene N. Schaefer, Esperance A. Brisac, Cynthia Chevaliez, Stephane Wambua, Daniel Peng, Lee F. Lin, Wenyu Chung, Raymond T. TI EFTUD2 regulates hepatitis C virus replication through the RIG-I/MDA5 pathway SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Zhu, Chuanlong; Hong, Jian; Zhao, Lei; Chusri, Pattranuch; Jilg, Nikolaus; Fusco, Dahlene N.; Schaefer, Esperance A.; Brisac, Cynthia; Chevaliez, Stephane; Wambua, Daniel; Peng, Lee F.; Lin, Wenyu; Chung, Raymond T.] Harvard Univ, Gastrointestinal Unit, Massachusetts Gen Hosp, Sch Med, 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 197 BP 306A EP 306A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252201197 ER PT J AU Curry, MP Forns, X Chung, RT Terrault, N Brown, RS Fenkel, JM Gordon, FD O'Leary, JG Kuo, A Schiano, TD Everson, GT Schiff, ER Befeler, A McHutchison, JG Symonds, WT Denning, JM McNair, L Arterburn, S Moonka, D Gane, EJ Afdhal, NH AF Curry, Michael P. Forns, Xavier Chung, Raymond T. Terrault, Norah Brown, Robert S. Fenkel, Jonathan M. Gordon, Fredric D. O'Leary, Jacqueline G. Kuo, Alexander Schiano, Thomas D. Everson, Gregory T. Schiff, Eugene R. Befeler, Alex McHutchison, John G. Symonds, William T. Denning, Jill M. McNair, Lindsay Arterburn, Sarah Moonka, Dilip Gane, Edward J. Afdhal, Nezam H. TI Pretransplant Sofosbuvir and Ribavirin to Prevent Recurrence of HCV Infection after Liver Transplantation SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Curry, Michael P.; Afdhal, Nezam H.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Forns, Xavier] Hosp Clin Barcelona, Liver Unit, Barcelona, Spain. [Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Terrault, Norah] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Brown, Robert S.] Columbia Univ, New York, NY USA. [Fenkel, Jonathan M.] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Gordon, Fredric D.] Lahey Clin Fdn, Burlington, MA USA. [O'Leary, Jacqueline G.] Baylor Univ, Med Ctr, Dallas, TX USA. [Kuo, Alexander] Univ Calif San Diego, La Jolla, CA 92093 USA. [Schiano, Thomas D.] Mt Sinai Sch Med, New York, NY USA. [Everson, Gregory T.] Univ Colorado, Denver, CO 80202 USA. [Schiff, Eugene R.] Univ Miami, Miami, FL USA. [Befeler, Alex] St Louis Univ, St Louis, MO 63103 USA. [McHutchison, John G.; Symonds, William T.; Denning, Jill M.; McNair, Lindsay; Arterburn, Sarah] Gilead Sci Inc, Foster City, CA 94404 USA. [Moonka, Dilip] Henry Ford Hlth Syst, Detroit, MI USA. [Gane, Edward J.] Auckland City Hosp, Auckland, New Zealand. NR 0 TC 32 Z9 32 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2013 VL 58 SU 1 SI SI MA 213 BP 314A EP 315A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252201213 ER PT J AU Hong, J Yuan, YF Wang, JP Liao, Y Zou, RH Zhu, CL Li, BK Liang, Y Huang, PZ Lin, WY Dai, JL Chung, RT AF Hong, Jian Yuan, Yunfei Wang, Jianping Liao, Yadi Zou, Ruhai Zhu, Chuanlong Li, Binkui Liang, Yi Huang, Pinzhu Lin, Wenyu Dai, Jia Le Chung, Raymond T. TI SYK(L) and its splicing variant SYK(S) exert opposing roles in hepatocellular carcinoma SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Hong, Jian; Yuan, Yunfei; Liao, Yadi; Zou, Ruhai; Li, Binkui; Liang, Yi; Huang, Pinzhu] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510275, Guangdong, Peoples R China. [Hong, Jian; Zhu, Chuanlong; Lin, Wenyu; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Wang, Jianping] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Surg, Guangzhou 510275, Guangdong, Peoples R China. [Dai, Jia Le] Univ Texas MD Anderson Canc Ctr, Div Pharm, Houston, TX 77030 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 234 BP 324A EP 325A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252201234 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 Macrophage Immunoregulatory Galectin-9 Production is increased by Contact with Hepatitis C Virus-infected Hepatocytes and Differentiation SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC 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 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 235 BP 325A EP 325A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252201235 ER PT J AU Lin, WY Zhu, CL Hong, J Zhao, L Xu, QK Chusri, P Jilg, N Fusco, DN Schaefer, EA Brisac, C Peng, LF Chung, RT AF Lin, Wenyu Zhu, Chuanlong Hong, Jian Zhao, Lei Xu, Qikai Chusri, Pattranuch Jilg, Nikolaus Fusco, Dahlene N. Schaefer, Esperance A. Brisac, Cynthia Peng, Lee F. Chung, Raymond T. TI The anti-HCV gene SART1 regulates IFN stimulated genes through nonclassical mechanisms SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Lin, Wenyu; Zhu, Chuanlong; Hong, Jian; Zhao, Lei; Chusri, Pattranuch; Jilg, Nikolaus; Fusco, Dahlene N.; Schaefer, Esperance A.; Brisac, Cynthia; Peng, Lee F.; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Xu, Qikai] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Genet, Boston, MA 02115 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 240 BP 327A EP 328A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252201240 ER PT J AU Koch, DG Battenhouse, H Durkalski, V Lee, WM Liou, IW Fix, OK Ganger, D Fontana, RJ Schilsky, ML McGuire, BM Chung, RT Reddy, R Stravitz, RT Han, SHB AF Koch, David G. Battenhouse, Holly Durkalski, Valerie Lee, William M. Liou, Iris W. Fix, Oren K. Ganger, Daniel Fontana, Robert J. Schilsky, Michael L. McGuire, Brendan M. Chung, Raymond T. Reddy, Rajender Stravitz, R. Todd Han, Steven-Huy B. TI The Natural History of Severe Acute Liver Injury (ALI) SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Koch, David G.] Med Univ S Carolina, Div Gastroenterol & Hepatol, Charleston, SC 29425 USA. [Battenhouse, Holly; Durkalski, Valerie] Med Univ S Carolina, Charleston, SC 29425 USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Liou, Iris W.] Univ Washington, Seattle, WA 98195 USA. [Fix, Oren K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ganger, Daniel] Northwestern Univ, Sch Med, Chicago, IL USA. [Fontana, Robert J.] Univ Michigan, Med Ctr, New Haven, CT USA. [Schilsky, Michael L.] Yale Univ, Sch Med, New Haven, CT USA. [McGuire, Brendan M.] Univ Alabama Birmingham, Birmingham, AL USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Reddy, Rajender] Univ Penn, Philadelphia, PA 19104 USA. [Stravitz, R. Todd] Virginia Commonwealth Univ, Richmond, VA USA. [Han, Steven-Huy B.] Univ Calif Los Angeles, Los Angeles, CA 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 307 BP 358A EP 359A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252201307 ER PT J AU Alvarez, NN Machaidze, Z Schuetz, C Ndishabandi, D Alessandrini, A Sachs, D Buhler, LH Markmann, J Yeh, H AF Alvarez, Nalu Navarro Machaidze, Zurab Schuetz, Christian Ndishabandi, Dorothy Alessandrini, Alessandro Sachs, David Buhler, Leo H. Markmann, James Yeh, Heidi TI Neutrophilia and High IL-6 Levels are Associated with Impaired Survival and Liver Regeneration SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Alvarez, Nalu Navarro; Machaidze, Zurab; Schuetz, Christian; Ndishabandi, Dorothy; Alessandrini, Alessandro; Sachs, David; Markmann, James; Yeh, Heidi] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Alvarez, Nalu Navarro; Machaidze, Zurab; Sachs, David] Massachusetts Gen Hosp, TBRC, Boston, MA 02114 USA. [Buhler, Leo H.] Univ Geneva, Geneva, Switzerland. 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 311 BP 361A EP 361A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252201311 ER PT J AU Izamis, ML Keravnou, C Christofides, D Averkiou, MA AF Izamis, Maria-Louisa Keravnou, Christina Christofides, Damianos Averkiou, Michalakis A. TI Quantification of liver perfusion is a sensitive approach to non-invasive evaluation of donor liver viability SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Izamis, Maria-Louisa; Keravnou, Christina; Christofides, Damianos; Averkiou, Michalakis A.] Univ Cyprus, Nicosia, Cyprus. [Izamis, Maria-Louisa] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Averkiou, Michalakis A.] Univ Washington, Seattle, WA 98195 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 332 BP 371A EP 371A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252201332 ER PT J AU Chaturantabut, S Cutting, CC Goessling, W North, TE AF Chaturantabut, Saireudee Cutting, Claire C. Goessling, Wolfram North, Trista E. TI The novel membrane estrogen receptor GPER positively regulates liver growth during development SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Chaturantabut, Saireudee] Harvard Univ, MCB, Cambridge, MA 02138 USA. [Cutting, Claire C.; Goessling, Wolfram] Brigham & Womens Hosp, Boston, MA 02115 USA. [North, Trista E.] PaBeth Israel 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 538 BP 465A EP 465A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252202142 ER PT J AU Mellinger, J Pencina, KM Massaro, JM Hoffmann, U Seshadri, S Fox, CS O'Donnell, CJ Speliotes, EK AF Mellinger, Jessica Pencina, Karol M. Massaro, Joseph M. Hoffmann, Udo Seshadri, Sudha Fox, Caroline S. O'Donnell, Christopher J. Speliotes, Elizabeth K. TI Nonalcoholic Fatty Liver Disease Associates with Cardiovascular Disease Outcomes: The Framingham Heart Study SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Mellinger, Jessica; Speliotes, Elizabeth K.] Univ Michigan, Ann Arbor, MI 48109 USA. [Pencina, Karol M.] Boston Univ, Stat & Consulting Unit, Boston, MA 02215 USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA USA. [Seshadri, Sudha] Boston Univ, Boston, MA 02215 USA. [Seshadri, Sudha; Fox, Caroline S.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Framingham, MA USA. [Speliotes, Elizabeth K.] Univ Michigan Hosp, Ann Arbor, MI 48109 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 579 BP 484A EP 485A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252202183 ER PT J AU Bril, F Lomonaco, R Orsak, B Chang, Z Ortiz-Lopez, C Hecht, J Tio, F Cusi, K AF Bril, Fernando Lomonaco, Romina Orsak, Beverly Chang, Zhi Ortiz-Lopez, Carolina Hecht, Joan Tio, Fermin Cusi, Kenneth TI Role of plasma FGF21 as a biomarker for nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Bril, Fernando; Lomonaco, Romina; Cusi, Kenneth] Univ Florida, Gainesville, FL USA. [Orsak, Beverly; Chang, Zhi; Ortiz-Lopez, Carolina; Hecht, Joan; Tio, Fermin; Cusi, Kenneth] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Hecht, Joan; Tio, Fermin] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 3 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2013 VL 58 SU 1 SI SI MA 585 BP 487A EP 487A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252202189 ER PT J AU Bril, F Lomonaco, R Orsak, B Hecht, J Ortiz-Lopez, C Hardies, J Tio, F Cusi, K AF Bril, Fernando Lomonaco, Romina Orsak, Beverly Hecht, Joan Ortiz-Lopez, Carolina Hardies, Jean Tio, Fermin Cusi, Kenneth TI Predictors of response after extended pioglitazone treatment in patients with prediabetes or T2DM and nonalcoholic steatohepatitis (NASH) SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Bril, Fernando; Lomonaco, Romina; Hardies, Jean; Cusi, Kenneth] Univ Florida, Gainesville, FL USA. [Orsak, Beverly; Hecht, Joan; Ortiz-Lopez, Carolina; Tio, Fermin; Cusi, Kenneth] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Hecht, Joan; Tio, Fermin] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 639 BP 513A EP 514A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252202243 ER PT J AU Khalili, M Sanyal, AJ Cloonan, YK Ghany, MG Kim, WR Chung, RT Terrault, N Brunt, EM Lau, D Lisker-Melman, M Lok, AS AF Khalili, Mandana Sanyal, Arun J. Cloonan, Yona K. Ghany, Marc G. Kim, W. Ray Chung, Raymond T. Terrault, Norah Brunt, Elizabeth M. Lau, Daryl Lisker-Melman, Mauricio Lok, Anna S. TI Factors associated with diabetes and prediabetes in HBV-infected patients residing in North America: Results from the Adult Cohort Study of the NIDDK-Sponsored Hepatitis B Research Network (HBRN) SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Khalili, Mandana; Terrault, Norah] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Sanyal, Arun J.] Virginia Commonwealth Univ, Richmond, VA USA. [Cloonan, Yona K.] Univ Pittsburgh, Pittsburgh, PA USA. [Ghany, Marc G.] NIH, Bethesda, MD 20892 USA. [Kim, W. Ray] Mayo Clin, Bethesda, MD USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brunt, Elizabeth M.; Lisker-Melman, Mauricio] Washington Univ, St Louis, MO USA. [Lau, Daryl] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 638 BP 513A EP 513A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252202242 ER PT J AU Bril, F Lomonaco, R Orsak, B Subbarayan, S Kadiyala, S Ortiz-Lopez, C Webb, A Cusi, K AF Bril, Fernando Lomonaco, Romina Orsak, Beverly Subbarayan, Sreevidya Kadiyala, Sushma Ortiz-Lopez, Carolina Webb, Amy Cusi, Kenneth TI Is there a link between hypothyroidism and nonalcoholic fatty liver disease? SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Bril, Fernando; Lomonaco, Romina; Subbarayan, Sreevidya; Kadiyala, Sushma; Cusi, Kenneth] Univ Florida, Gainesville, FL USA. [Orsak, Beverly; Ortiz-Lopez, Carolina; Webb, Amy; Cusi, Kenneth] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Webb, Amy] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 656 BP 521A EP 522A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252202260 ER PT J AU Bril, F Lomonaco, R Orsak, B Ortiz-Lopez, C Biernacki, D Klaczak, A Chang, Z Hardies, J Cusi, K AF Bril, Fernando Lomonaco, Romina Orsak, Beverly Ortiz-Lopez, Carolina Biernacki, Diane Klaczak, Ashley Chang, Zhi Hardies, Jean Cusi, Kenneth TI Vitamin D deficiency and development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Bril, Fernando; Lomonaco, Romina; Biernacki, Diane; Klaczak, Ashley; Cusi, Kenneth] Univ Florida, Gainesville, FL USA. [Orsak, Beverly; Ortiz-Lopez, Carolina; Chang, Zhi; Hardies, Jean; Cusi, Kenneth] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Biernacki, Diane] Malcom Randall Vet Adm Med Ctr, Gainesville, FL USA. [Hardies, Jean] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 2 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 657 BP 522A EP 522A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252202261 ER PT J AU Bettermann, K Mehta, AK Lederer, E Ernst, C Kessler, SM Chen, XT Hoshida, Y Bardeesy, N Fuchs, BC Tanabe, KK Muller, H Svendova, V Schimek, MG Mach, M Speicher, MR Mahajan, V Stumptner, C Thueringer, A Stojakovic, T Longerich, T Schirmacher, P Magin, TM Strnad, P Fuchs, CD Trauner, M Spilka, R Kiemer, AK Teufel, A Maass, T Moriggl, R Campbell, JS Thorgeirsson, SS Stauffer, J Karin, M Llovet, JM Zatloukal, K Lackner, C Hayback, J AF Bettermann, Kira Mehta, Anita Kuldeep Lederer, Eva Ernst, Christina Kessler, Sonja M. Chen, Xintong Hoshida, Yujin Bardeesy, Nabeel Fuchs, Bryan C. Tanabe, Kenneth K. Mueller, Heimo Svendova, Vendula Schimek, Michael G. Mach, Monika Speicher, Michael R. Mahajan, Vineet Stumptner, Cornelia Thueringer, Andrea Stojakovic, Tatjana Longerich, Thomas Schirmacher, Peter Magin, Thomas M. Strnad, Pavel Fuchs, Claudia D. Trauner, Michael Spilka, Rita Kiemer, Alexandra K. Teufel, Andreas Maass, Thorsten Moriggl, Richard Campbell, Jean S. Thorgeirsson, Snorri S. Stauffer, Jim Karin, Michael Llovet, Josep M. Zatloukal, Kurt Lackner, Carolin Haybaeck, Johannes TI Steatohepatitits-associated Hepatocellular Carcinoma: Evidence of a Keratinopathy SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Bettermann, Kira; Mehta, Anita Kuldeep; Lederer, Eva; Ernst, Christina; Kessler, Sonja M.; Mueller, Heimo; Mahajan, Vineet; Stumptner, Cornelia; Thueringer, Andrea; Zatloukal, Kurt; Lackner, Carolin; Haybaeck, Johannes] Med Univ Graz, Inst Pathol, Graz, Austria. [Kessler, Sonja M.; Kiemer, Alexandra K.] Univ Saarland, Dept Pharm, Saarbrucken, Germany. [Chen, Xintong; Hoshida, Yujin; Llovet, Josep M.] Icahn Sch Med Mt Sinai, Div Liver Dis, Tisch Canc Inst, Liver Canc Program, New York, NY USA. [Bardeesy, Nabeel; Fuchs, Bryan C.; Tanabe, Kenneth K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc Res, Boston, MA USA. [Svendova, Vendula; Schimek, Michael G.] Med Univ Graz, Inst Med Informat Stat & Documentat, Graz, Austria. [Mach, Monika; Speicher, Michael R.] Med Univ Graz, Inst Human Genet, Graz, Austria. [Stojakovic, Tatjana] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria. [Longerich, Thomas; Schirmacher, Peter] Univ Heidelberg Hosp, Inst Pathol, Heidelberg, Germany. [Magin, Thomas M.] Univ Leipzig, Translat Ctr Regenerat Med Leipzig, D-04109 Leipzig, Germany. [Strnad, Pavel] Univ Hosp RWTH Aachen, Dept Internal Med 3, Aachen, Germany. [Fuchs, Claudia D.; Trauner, Michael] Med Univ Vienna, Dept Internal Med 3, Div Gastroenterol & Hepatol, Vienna, Austria. [Spilka, Rita] Gen Hosp Zams, Pathol Lab, Zams, Austria. [Teufel, Andreas; Maass, Thorsten] Univ Clin Regensburg, Clin & Polyclin Internal Med 1, Regensburg, Germany. [Moriggl, Richard] Ludwig Boltzmann Inst Canc Res LBI CR, Vienna, Austria. [Campbell, Jean S.] Univ Washington, Dept Med Pathol, Seattle, WA 98195 USA. [Thorgeirsson, Snorri S.] NCI, Lab Expt Carcinogenesis, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Cologne, Inst Genet, Cologne, Germany. [Stauffer, Jim] NCI, Mouse Canc Genet Program, Genet Modifiers Tumorigenesis Sect, Ctr Canc Res, Frederick, MD 21701 USA. [Karin, Michael] Univ Calif San Diego, Sch Med, Dept Pharmacol, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA. [Llovet, Josep M.] Hosp Clin Barcelona, Inst Invest Biomed, CIBERehd,Liver Unit, Hepatocellular Carcinoma Translat Res Lab,Barcelo, Barcelona, Spain. RI Kiemer, Alexandra/I-9300-2012 OI Kiemer, Alexandra/0000-0002-7224-9900 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 702 BP 543A EP 543A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252202306 ER PT J AU Luther, J Scichilone, J Garber, J Khalili, H Peng, LF Chevaliez, S Chung, RT Patel, SJ AF Luther, Jay Scichilone, John Garber, John Khalili, Hamed Peng, Lee F. Chevaliez, Stephane Chung, Raymond T. Patel, Suraj J. TI Crosstalk between the liver and intestine contributes to NASH pathogenesis SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Luther, Jay; Garber, John; Khalili, Hamed; Peng, Lee F.; Chevaliez, Stephane; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Scichilone, John; Patel, Suraj J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Scichilone, John; Patel, Suraj J.] Shriners Hosp Crippled Children, 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 732 BP 556A EP 556A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252202336 ER PT J AU Schippers, M Post, E Cetintas, A Reker-Smit, C Malo, MS Hodin, RA Millan, JL Beljaars, L Poelstra, K AF Schippers, Marlies Post, Eduard Cetintas, Aysegul Reker-Smit, Catharina Malo, Madhu S. Hodin, Richard A. Millan, Jose L. Beljaars, Leonie Poelstra, Klaas TI Intrahepatic alkaline phosphatase attenuates LPS-mediated effects during liver fibrosis SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Schippers, Marlies; Post, Eduard; Cetintas, Aysegul; Reker-Smit, Catharina; Beljaars, Leonie; Poelstra, Klaas] Univ Groningen, Dept Pharmacokinet Toxicol & Targeting, Groningen, Netherlands. [Malo, Madhu S.; Hodin, Richard A.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Millan, Jose L.] Sanford Childrens Hlth Res Ctr, Sanford Burnham Med Res Inst, La Jolla, 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 783 BP 579A EP 579A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252202387 ER PT J AU Chang, MF Dominitz, JA Ioannou, GN Forsberg, CW Boyko, EJ Sporleder, JL Smith, NL AF Chang, Michael F. Dominitz, Jason A. Ioannou, George N. Forsberg, Christopher W. Boyko, Edward J. Sporleder, Jennifer L. Smith, Nicholas L. TI Elevated prevalence of hepatitis B chronic infection and exposure in users of United States Veterans Medical Centers SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Chang, Michael F.] OHSU PVAMC, Portland, OR USA. [Chang, Michael F.] Portland VA Med Ctr, Northwest Hepatitis Resource Ctr C, Portland, OR USA. [Dominitz, Jason A.; Ioannou, George N.] VA Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle, WA USA. [Dominitz, Jason A.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Sporleder, Jennifer L.] VA Puget Sound Hlth Care Syst, Northwest Hepatitis Resource Ctr C, Seattle, WA USA. [Forsberg, Christopher W.; Sporleder, Jennifer L.; Smith, Nicholas L.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [Boyko, Edward J.; Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 876 BP 623A EP 624A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252203044 ER PT J AU Hammond, SP Ho, VT Ukomadu, C Baden, LR Marty, FM AF Hammond, Sarah P. Ho, Vincent T. Ukomadu, Chinweike Baden, Lindsey R. Marty, Francisco M. TI Resolution of Hepatitis B Virus (HBV) Infection is Common after Antiviral Therapy in Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Recipients who Develop Reverse Seroconversion SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Hammond, Sarah P.; Baden, Lindsey R.; Marty, Francisco M.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Hammond, Sarah P.; Ho, Vincent T.; Baden, Lindsey R.; Marty, Francisco M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ukomadu, Chinweike] Brigham & Womens Hosp, Div Gastroenterol, 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 882 BP 626A EP 627A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252203050 ER PT J AU Wu, Y Johnson, KB Lopez, J Zheng, H Roccaro, G Muiru, A Ufere, N Kattan, O Chung, RT AF Wu, Ying Johnson, Kara B. Lopez, Joanna Zheng, Hui Roccaro, Giorgio Muiru, Anthony Ufere, Nneka Kattan, Omar Chung, Raymond T. TI Poor Adherence to AASLD Guidelines for Chronic Hepatitis B Management in a Large Academic Medical Center SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Wu, Ying; Johnson, Kara B.; Lopez, Joanna; Zheng, Hui; Roccaro, Giorgio; Muiru, Anthony; Ufere, Nneka; Kattan, Omar; Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Johnson, Kara B.] Harvard Univ, Sch Med, 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 902 BP 636A EP 636A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252203070 ER PT J AU Mangia, A Kugelmas, M Everson, GT Hinestrosa, F Ma, J McNally, J Brainard, DM Symonds, WT McHutchison, JG Gane, EJ Shafran, SD Chung, RT Lawitz, E AF Mangia, Alessandra Kugelmas, Marcelo Everson, Gregory T. Hinestrosa, Federico Ma, Julie McNally, John Brainard, Diana M. Symonds, William T. McHutchison, John G. Gane, Edward J. Shafran, Stephen D. Chung, Raymond T. Lawitz, Eric TI Virologic Response Rates to Sofosbuvir-Containing Regimens Are Similar in Patients With and Without Traditional Negative Predictive Factors: A Retrospective Analysis of Phase 3 Data SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Mangia, Alessandra] IRCCS Osped Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy. [Kugelmas, Marcelo] South Denver Gastroenterol, Englewood, CA USA. [Everson, Gregory T.] Univ Colorado, Aurora, CO USA. [Hinestrosa, Federico] Orlando Immunol Ctr, Orlando, FL USA. [Ma, Julie; McNally, John; Brainard, Diana M.; Symonds, William T.; McHutchison, John G.] Gilead Sci Inc, Foster City, CA 94404 USA. [Gane, Edward J.] Auckland City Hosp, Auckland, New Zealand. [Shafran, Stephen D.] Univ Alberta Hosp, Edmonton, AB T6G 2B7, Canada. [Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lawitz, Eric] Texas Liver Inst, San Antonio, TX USA. NR 0 TC 6 Z9 6 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 1115 BP 752A EP 753A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252203281 ER PT J AU Vagefi, PA Dodge, JL Feng, S Roberts, JP AF Vagefi, Parsia A. Dodge, Jennifer L. Feng, Sandy Roberts, John P. TI Regional Importer or Exporter? Multiple Listings as Insight into the Geographic Inequity Facing Liver Transplant Candidates SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Vagefi, Parsia A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Dodge, Jennifer L.; Feng, Sandy; Roberts, John P.] Univ Calif San Francisco, San Francisco, CA 94143 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 1136 BP 764A EP 764A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252203302 ER PT J AU Kohn, R Kratz, JR Markmann, J Vagefi, PA AF Kohn, Rachel Kratz, Johannes R. Markmann, James Vagefi, Parsia A. TI The "exported" liver transplant candidate: A reflection of geographic inequity in liver allocation SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Kohn, Rachel; Kratz, Johannes R.; Markmann, James; Vagefi, Parsia A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 1157 BP 774A EP 775A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252203323 ER PT J AU Basu, P Shah, NJ Rahman, MA Siriki, R Farhat, S AF Basu, Patrick Shah, Niraj J. Rahman, Md A. Siriki, Ravi Farhat, Sakina TI Restless Leg Syndrome (RLS) is associated with Hepatic Encephalopathy (HE) in decompensated cirrhosis. A clinical pilot study SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Basu, Patrick; Farhat, Sakina] Columbia Univ, Sch Phys & Surg, Forest Hills, NY USA. [Basu, Patrick; Rahman, Md A.; Siriki, Ravi] NSLIJHS Hofstra North Shore LIJ Sch Med, New York, NY USA. [Shah, Niraj J.] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2013 VL 58 SU 1 SI SI MA 1355 BP 867A EP 867A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252204138 ER PT J AU Tartaglione, E Derleth, M Yu, L Ioannou, GN AF Tartaglione, Erica Derleth, Mark Yu, Lei Ioannou, George N. TI Can computerized brain training games be used to identify early cognitive impairment in cirrhosis? SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Tartaglione, Erica; Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Derleth, Mark; Yu, Lei; Ioannou, George N.] Univ Washington, Seattle, WA 98195 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 1391 BP 884A EP 884A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252204174 ER PT J AU King, LY Johnson, KB Zheng, H Wei, L Gudewicz, T Tokunbo, A Ufere, N Tanabe, K Fuchs, BC Chung, RT AF King, Lindsay Y. Johnson, Kara B. Zheng, Hui Wei, Lan Gudewicz, Thomas Tokunbo, Ajayi Ufere, Nneka Tanabe, Kenneth Fuchs, Bryan C. Chung, Raymond T. TI A Polymorphism in the EGF Gene Independently Predicts Hepatic Outcomes in HCV-Related Cirrhosis SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [King, Lindsay Y.; Johnson, Kara B.; Ufere, Nneka; Chung, Raymond T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Johnson, Kara B.] Harvard Univ, Sch Med, Boston, MA USA. [Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Wei, Lan; Gudewicz, Thomas; Tanabe, Kenneth; Fuchs, Bryan C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tokunbo, Ajayi] Salem Hosp, 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 1430 BP 902A EP 902A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252204213 ER PT J AU Schaefer, EA Meixiong, J Motola, D Deik, A Fusco, DN Lin, C Jilg, N Chevaliez, S Brisac, C Chusri, P Lin, WY Clish, CB Musunuru, K Cowan, CA Chung, RT Peng, LF AF Schaefer, Esperance A. Meixiong, James Motola, Daniel Deik, Amy Fusco, Dahlene N. Lin, Carol Jilg, Nikolaus Chevaliez, Stephane Brisac, Cynthia Chusri, Pattranuch Lin, Wenyu Clish, Clary B. Musunuru, Kiran Cowan, Chad A. Chung, Raymond T. Peng, Lee F. TI Loss of apolipoprotein B100 decreases viral infectivity and depletes cholesterol from HCV virions SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Schaefer, Esperance A.; Motola, Daniel; Fusco, Dahlene N.; Jilg, Nikolaus; Chevaliez, Stephane; Brisac, Cynthia; Chusri, Pattranuch; Lin, Wenyu; Chung, Raymond T.; Peng, Lee F.] Massachusetts Gen Hosp, Med GI Unit, Boston, MA 02114 USA. [Deik, Amy; Clish, Clary B.] Broad Inst, Boston, MA USA. [Musunuru, Kiran; Cowan, Chad A.] Harvard Stem Cell Inst, Boston, MA USA. [Meixiong, James; Lin, Carol] Harvard Univ, Boston, MA 02115 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 1487 BP 929A EP 929A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252204270 ER PT J AU Chevaliez, S Brisac, C Schaefer, EA Wambua, D Jilg, N Luther, J Chusri, P Zablocki, L Lin, WY Peng, LF Fusco, DN Chung, RT AF Chevaliez, Stephane Brisac, Cynthia Schaefer, Esperance A. Wambua, Daniel Jilg, Nikolaus Luther, Jay Chusri, Pattranuch Zablocki, Laurent Lin, Wenyu Peng, Lee F. Fusco, Dahlene N. Chung, Raymond T. TI Role of the PDIP1 protein in the IFN response during hepatitis C virus infection: impact of PPAR nuclear receptors SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Chevaliez, Stephane; Brisac, Cynthia; Schaefer, Esperance A.; Wambua, Daniel; Jilg, Nikolaus; Luther, Jay; Chusri, Pattranuch; Zablocki, Laurent; Lin, Wenyu; Peng, Lee F.; Fusco, Dahlene N.; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Chevaliez, Stephane] Univ Hosp Henri Mondor, Creteil, France. [Chevaliez, Stephane] Univ Hosp Henri Mondor, INSERM U955, 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 1490 BP 930A EP 930A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252204273 ER PT J AU Peng, LF Meixiong, J Deik, A Schaefer, EA Jilg, N Chusri, P Brisac, C Chevaliez, S Zhu, CL Luther, J Wambua, D Fusco, DN Lin, WY Clish, CB Chung, RT AF Peng, Lee F. Meixiong, James Deik, Amy Schaefer, Esperance A. Jilg, Nikolaus Chusri, Pattranuch Brisac, Cynthia Chevaliez, Stephane Zhu, Chuanlong Luther, Jay Wambua, Daniel Fusco, Dahlene N. Lin, Wenyu Clish, Clary B. Chung, Raymond T. TI HMG-CoA Reductase Inhibition Alters the Lipidome and Infectious Properties of HCV Virus Particles SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Peng, Lee F.; Meixiong, James; Schaefer, Esperance A.; Jilg, Nikolaus; Chusri, Pattranuch; Brisac, Cynthia; Chevaliez, Stephane; Zhu, Chuanlong; Luther, Jay; Wambua, Daniel; Fusco, Dahlene N.; Lin, Wenyu; Chung, Raymond T.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. [Deik, Amy; Clish, Clary B.] Broad Inst, Cambridge, 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 1503 BP 936A EP 936A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252204286 ER PT J AU Zator, ZA Somsouk, M Zheng, H King, LY Lin, WY Hunt, PW Deeks, SG Chung, RT AF Zator, Zachary A. Somsouk, Ma Zheng, Hui King, Lindsay Y. Lin, Wenyu Hunt, Peter W. Deeks, Steven G. Chung, Raymond T. TI HIV infection is associated with elevated markers of hepatocyte apoptosis: a possible mechanism for accelerated HCV liver disease progression SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Zator, Zachary A.; Zheng, Hui] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Somsouk, Ma] UCSF, San Francisco, CA USA. [King, Lindsay Y.; Lin, Wenyu; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Hunt, Peter W.; Deeks, Steven G.] Univ Calif San Francisco, San Francisco, CA 94143 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 1529 BP 948A EP 948A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252204312 ER PT J AU Jilg, N Hatoum, IJ Greenawalt, DM Lin, WY Kaplan, LM Chung, RT AF Jilg, Nikolaus Hatoum, Ida J. Greenawalt, Danielle M. Lin, Wenyu Kaplan, Lee M. Chung, Raymond T. TI IL28B genotype is not associated with differential gene expression in a large cohort of patients without known HCV infection SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Jilg, Nikolaus; Hatoum, Ida J.; Lin, Wenyu; Kaplan, Lee M.; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, GI Unit, Boston, MA 02114 USA. [Hatoum, Ida J.; Kaplan, Lee M.] Massachusetts Gen Hosp, Obes Metab & Nutr Inst, Boston, MA 02114 USA. [Greenawalt, Danielle M.] Merck Res Labs, Boston, MA 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 1593 BP 976A EP 976A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252204376 ER PT J AU Berry, K Ioannou, GN AF Berry, Kristin Ioannou, George N. TI The association between transjugular intrahepatic portosystemic shunt and survival SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Berry, Kristin; Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Ioannou, George N.] Univ Washington, Seattle, WA 98195 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 1634 BP 996A EP 996A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252204417 ER PT J AU Tarlow, B Naugler, WE Orloff, SL Haft, A Grompe, M AF Tarlow, Branden Naugler, Willscott E. Orloff, Susan L. Haft, Annelise Grompe, Markus TI Repopulation of mouse liver with human hepatocytes from core biopsies: a new approach to modeling human liver diseases SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Tarlow, Branden; Naugler, Willscott E.; Haft, Annelise; Grompe, Markus] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Orloff, Susan L.] Portland VA Med Ctr, Portland, OR 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 1664 BP 1010A EP 1010A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252205014 ER PT J AU Watanabe, T Tokumoto, Y Hirooka, M Abe, M Onji, M Chung, RT Hiasa, Y AF Watanabe, Takao Tokumoto, Yoshio Hirooka, Masashi Abe, Masanori Onji, Morikazu Chung, Raymond T. Hiasa, Yoichi TI Protein kinase R modulates c-Fos and c-Jun signaling to promote proliferation of hepatocellular carcinoma with hepatitis C virus infection SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Watanabe, Takao; Tokumoto, Yoshio; Hirooka, Masashi; Abe, Masanori; Onji, Morikazu; Hiasa, Yoichi] Ehime Univ, Grad Sch Med, Dept Gastroenterol & Metabol, Toon, Japan. [Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 1822 BP 1082A EP 1082A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252205172 ER PT J AU Chen, YC Huang, YH Reiberger, T Huang, PG Lauwers, GY Zhu, AX Jain, RK Duda, DG AF Chen, Yunching Huang, Yuhui Reiberger, Thomas Huang, Peigen Lauwers, Gregory Y. Zhu, Andrew X. Jain, Rakesh K. Duda, Dan G. TI Differential effects of sorafenib on liver and hepatocellular carcinoma fibrosis mediated by SDF1 alpha/CXCR4 axis and Gr-1+myeloid cell infiltration SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Chen, Yunching; Huang, Yuhui; Reiberger, Thomas; Huang, Peigen; Jain, Rakesh K.; Duda, Dan G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Zhu, Andrew X.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 1839 BP 1089A EP 1090A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252205189 ER PT J AU Basu, P Shah, NJ Siriki, R Rahman, MA Farhat, S AF Basu, Patrick Shah, Niraj J. Siriki, Ravi Rahman, Md A. Farhat, Sakina TI Romiplostim's Effect to Optimize SVR with Telaprevir, Ribavirin, And Peg Interferon-alfa 2a in Thrombocytopenic Cirrhotics with Chronic Hepatitis C. A Placebo Controlled Prospective Clinical Trial: RESTRAINT C Trial SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Basu, Patrick; Farhat, Sakina] Columbia Univ Sch Phys & Surg, New York, NY USA. [Basu, Patrick; Siriki, Ravi; Rahman, Md A.] NSLIJHS Hofstra North Shore LIJ Sch Med, New York, NY USA. [Shah, Niraj J.] Mt Sinai, Icahn Sch Med, James J Peters VA Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2013 VL 58 SU 1 SI SI MA 1886 BP 1117A EP 1117A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252205236 ER PT J AU Saxena, V Yee, HS Catalli, L Wayne, EM Chua, J Monto, A Terrault, N AF Saxena, Varun Yee, Helen S. Catalli, Lisa Wayne, Elizabeth M. Chua, Joshua Monto, Alexander Terrault, Norah TI Protease-Inhibitor (PI) Triple Therapy (TT) in Mildly Decompensated Cirrhotics: Predictors of Treatment Discontinuation, Worsening Decompensation and Sustained Virologic Response SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Saxena, Varun; Yee, Helen S.; Catalli, Lisa; Wayne, Elizabeth M.; Monto, Alexander; Terrault, Norah] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Yee, Helen S.; Chua, Joshua; Monto, Alexander] San Francisco VA Med Ctr, San Francisco, CA 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 1969 BP 1161A EP 1161A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252205319 ER PT J AU Jang, JY Kim, SJ Cho, EK Jeong, SW Lee, YN Lee, SH Kim, SG Cha, SW Kim, YS Cho, YD Kim, HS Kim, BS Lin, WY Chung, RT AF Jang, Jae Young Kim, Seong-Jun Cho, Eun Kyung Jeong, Soung Won Lee, Yun Nah Lee, Sae Hwan Kim, Sang Gyune Cha, Sang-Woo Kim, Young Seok Cho, Young Deok Kim, Hong Soo Kim, Boo Sung Lin, Wenyu Chung, Raymond T. TI Hepatitis C virus infection elevates TRAIL-DR4/DR5-induced apoptosis via caspase-8 activation SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Jang, Jae Young; Cho, Eun Kyung; Jeong, Soung Won; Cha, Sang-Woo; Cho, Young Deok; Kim, Boo Sung] Soonchunhyang Univ, Inst Digest Res, Ctr Digest Dis, Dept Internal Med,Coll Med, Seoul, South Korea. [Lee, Sae Hwan; Kim, Hong Soo] Soonchunhyang Univ, Dept Internal Med, Coll Med, Cheonan, South Korea. [Lee, Yun Nah; Kim, Sang Gyune; Kim, Young Seok] Soonchunhyang Univ, Dept Internal Med, Coll Med, Puchon, South Korea. [Kim, Seong-Jun] Univ Calif San Diego, Dept Med, Div Infect Dis, San Diego, CA 92103 USA. [Lin, Wenyu; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 2008 BP 1180A EP 1180A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252205358 ER PT J AU Ojiro, K Kikuchi, M Park, JJ Bunchorntavakul, C Jones, LM Valiga, ME Kaplan, DE Nunes, F Reddy, R Chang, KM AF Ojiro, Keisuke Kikuchi, Masahiro Park, Jang-June Bunchorntavakul, Chalermrat Jones, Lisa M. Valiga, Mary E. Kaplan, David E. Nunes, Frederick Reddy, Rajender Chang, Kyong-Mi TI IL28B genotype defines differential immune costimulatory receptor expression in acute hepatitis C SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Ojiro, Keisuke; Kikuchi, Masahiro; Park, Jang-June; Bunchorntavakul, Chalermrat; Jones, Lisa M.; Valiga, Mary E.; Kaplan, David E.; Nunes, Frederick; Reddy, Rajender; Chang, Kyong-Mi] Univ Penn, Philadelphia, PA 19104 USA. [Ojiro, Keisuke; Kikuchi, Masahiro; Park, Jang-June; Valiga, Mary E.; Kaplan, David E.; Chang, Kyong-Mi] Philadelphia VA Med Ctr, Philadelphia, PA 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 2024 BP 1187A EP 1187A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252205374 ER PT J AU Beste, LA Ioannou, GN Yang, Y Chang, MF Ross, D Dominitz, JA AF Beste, Lauren A. Ioannou, George N. Yang, Yin Chang, Michael F. Ross, David Dominitz, Jason A. TI Improvement in use of hepatocellular carcinoma surveillance by a primary-care oriented computerized clinical reminder SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Beste, Lauren A.] VA Puget Sound Hlth Care Syst, Primary Care, Seattle, WA USA. [Beste, Lauren A.; Ioannou, George N.; Dominitz, Jason A.] Univ Washington, Seattle, WA 98195 USA. [Ioannou, George N.; Dominitz, Jason A.] VA Puget Sound Hlth Care Syst, Gastroenterol, Seattle, WA USA. [Chang, Michael F.] Portland VA Med Ctr, Hepatol, Portland, OR USA. [Ross, David] VA Cent Off, HIV Hepatitis C & Publ Hlth Pathogens Program, Washington, DC USA. [Chang, Michael F.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Yang, Yin] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 2037 BP 1193A EP 1193A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252205387 ER PT J AU Johnson, KB Campbell, EJ Chi, H Zheng, H King, LY Wu, Y deLemos, A Hurairah, A Corey, KE Richter, JM Chung, RT AF Johnson, Kara B. Campbell, Emily J. Chi, Heng Zheng, Hui King, Lindsay Y. Wu, Ying deLemos, Andrew Hurairah, Abu Corey, Kathleen E. Richter, James M. Chung, Raymond T. TI Diuretic Use is the Most Important Factor that Predicts Hospital Admissions in an Ambulatory Cirrhosis Cohort SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Johnson, Kara B.] Harvard Univ, Sch Med, Boston, MA USA. [Johnson, Kara B.; Campbell, Emily J.; King, Lindsay Y.; Wu, Ying; deLemos, Andrew; Corey, Kathleen E.; Richter, James M.; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. [Chi, Heng] Erasmus MC Med Ctr Rotterdam, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands. [Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Hurairah, Abu] Mt Auburn Hosp, Dept Med, 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 2038 BP 1193A EP 1194A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252205388 ER PT J AU Beste, LA Harp, BK Blais, RK Zickmund, S AF Beste, Lauren A. Harp, Bonnie K. Blais, Rebecca K. Zickmund, Susan TI "They Gotta Want to Live More Than They Want to Die": Primary Care Attitudes and Beliefs about Cirrhosis SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Beste, Lauren A.] VA Puget Sound Hlth Care Syst, Primary Care, Seattle, WA USA. [Harp, Bonnie K.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Blais, Rebecca K.] VA Puget Sound Hlth Care Syst, Mental Hlth, Seattle, WA USA. [Beste, Lauren A.] Univ Washington, Seattle, WA 98195 USA. [Zickmund, Susan] VA Pittsburgh Hlth Care Syst, Hlth Serv Res & Dev, Pittsburgh, PA USA. [Zickmund, Susan] Univ Pittsburgh, Dept Med & Clin & Translat Sci, Pittsburgh, PA 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 2061 BP 1204A EP 1205A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252206013 ER PT J AU King, LY Khalili, H Huang, E Chung, RT Chan, AT AF King, Lindsay Y. Khalili, Hamed Huang, Edward Chung, Raymond T. Chan, Andrew T. TI Statins Are Associated With a Reduced Risk of Liver Cancer: Data from a Large US Prospective Cohort Study SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC 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] Good Samaritan Hosp, San Jose, CA 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 2085 BP 1216A EP 1217A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252206037 ER PT J AU Fox, RK Marcus, S Merchante, N Kikuchi, L Minguez, B Vispo, E Harris, M Badshah, MB Jain, MK Page, EE Kaplan, DE Nelson, M Barrero, P Pineda, JA Brau, N AF Fox, Rena K. Marcus, Sonja Merchante, Nicolas Kikuchi, Luciana Minguez, Beatriz Vispo, Eugenia Harris, Marianne Badshah, Maaz B. Jain, Mamta K. Page, Emma E. Kaplan, David E. Nelson, Mark Barrero, Pablo Pineda, Juan A. Brau, Norbert TI Impact of Screening on Staging and Survival of Hepatocellular Carcinoma (HCC) in HIV/HCV-Coinfected Patients SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Fox, Rena K.] Univ Calif San Francicso, San Francisco, CA USA. [Marcus, Sonja; Badshah, Maaz B.; Brau, Norbert] Bronx VA Med Ctr, Bronx, NY USA. [Merchante, Nicolas; Pineda, Juan A.] Hosp Univ Valme, Seville, Spain. [Kikuchi, Luciana] Univ Sao Paulo, Sao Paulo, Brazil. [Minguez, Beatriz] Hosp Univ Vall dHebron, Barcelona, Spain. [Vispo, Eugenia; Barrero, Pablo] Hosp Carlos III, Madrid, Spain. [Harris, Marianne] St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. [Harris, Marianne] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Jain, Mamta K.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Page, Emma E.; Nelson, Mark] Chelsea & Westminster Hosp, London, England. [Page, Emma E.; Nelson, Mark] Univ London Imperial Coll Sci Technol & Med, London, England. [Kaplan, David E.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Kaplan, David E.] Univ Penn, Philadelphia, PA 19104 USA. [Brau, Norbert] Mt Sinai Sch Med, New York, NY USA. RI Minguez, Beatriz/N-4456-2014 OI Minguez, Beatriz/0000-0002-7276-9666 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 2125 BP 1236A EP 1236A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252206077 ER PT J AU Marks, KM Page, EE Merchante, N Kikuchi, LO Minguez, B Vispo, E Harris, M Badshah, MB Jain, MK Marcus, S Kaplan, DE Nelson, M Barrero, P Pineda, JA Brau, N AF Marks, Kristen M. Page, Emma E. Merchante, Nicolas Kikuchi, Luciana O. Minguez, Beatriz Vispo, Eugenia Harris, Marianne Badshah, Maaz B. Jain, Mamta K. Marcus, Sonja Kaplan, David E. Nelson, Mark Barrero, Pablo Pineda, Juan A. Brau, Norbert TI Trends of Hepatocellular Carcinoma (HCC) in HIV-Infected Patients over Time, 1995-2013 SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Marks, Kristen M.] Weill Cornell Coll Med, New York, NY USA. [Badshah, Maaz B.; Marcus, Sonja; Brau, Norbert] Bronx VA Med Ctr, Bronx, NY USA. [Merchante, Nicolas; Pineda, Juan A.] Hosp Univ Valme, Seville, Spain. [Harris, Marianne] St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. [Harris, Marianne] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Kikuchi, Luciana O.] Univ Sao Paulo, Sao Paulo, Brazil. [Minguez, Beatriz] Hosp Univ Vall dHebron, Barcelona, Spain. [Vispo, Eugenia; Barrero, Pablo] Hosp Carlos III, Madrid, Spain. [Jain, Mamta K.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Nelson, Mark] Chelsea & Westminster Hosp, London, England. [Nelson, Mark] Univ London Imperial Coll Sci Technol & Med, London, England. [Kaplan, David E.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Kaplan, David E.] Univ Penn, Philadelphia, PA 19104 USA. [Brau, Norbert] Mt Sinai Sch Med, New York, NY USA. RI Minguez, Beatriz/N-4456-2014 OI Minguez, Beatriz/0000-0002-7276-9666 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 2151 BP 1249A EP 1249A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252206103 ER PT J AU Ioannou, GN Bryson, C Weiss, NS Boyko, EJ AF Ioannou, George N. Bryson, Christopher Weiss, Noel S. Boyko, Edward J. TI Antiretroviral medications, lipodystrophy and cirrhosis in HIV-infected patients SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Ioannou, George N.; Bryson, Christopher; Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Ioannou, George N.; Bryson, Christopher; Weiss, Noel S.; Boyko, Edward J.] Univ Washington, Seattle, WA 98195 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 2216 BP 1279A EP 1280A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252206168 ER PT J AU Yu, L Morishima, C Ioannou, GN AF Yu, Lei Morishima, Chihiro Ioannou, George N. TI Dietary cholesterol intake is associated with death and liver transplantation in chronic hepatitis C virus infection: Analysis of extended follow-up data from the HALT-C trial SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Yu, Lei; Morishima, Chihiro; Ioannou, George N.] Univ Washington, Seattle, WA 98195 USA. [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 2219 BP 1281A EP 1281A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252206171 ER PT J AU Dieperink, E Fuller, B Ho, SB Thuras, P McMaken, K Shira, K Lenox, R Wasil, MM Isenhart, C Morgan, TR Hauser, P AF Dieperink, Eric Fuller, Bret Ho, Samuel B. Thuras, Paul McMaken, Kelly Shira, Kern Lenox, Rebecca Wasil, Michelene M. Isenhart, Carl Morgan, Timothy R. Hauser, Peter TI Association of self-reported change in alcohol use behavior with changes in percent carbohydrate deficient transferring (%CDT), ethyl glucuronide (EtG) and ethyl sulfate (EtS) levels in Veterans with Hepatitis C SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Ho, Samuel B.; Wasil, Michelene M.] VA San Diego Healthcare Syst, San Diego, CA USA. [Fuller, Bret; Lenox, Rebecca] Portland VA Med Ctr, Portland, OR USA. [Dieperink, Eric; Thuras, Paul; McMaken, Kelly; Isenhart, Carl] Minneapolis VA Med Ctr, Minneapolis, MN USA. [Shira, Kern; Morgan, Timothy R.; Hauser, Peter] Long Beach VA Med Ctr, Long Beach, CA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2013 VL 58 SU 1 SI SI MA 2229 BP 1286A EP 1286A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252206181 ER PT J AU Onofrey, S Aneja, J Haney, GA Nagami, EH DeMaria, A Bowen, MJ Cocoros, N McGovern, BH Church, DR Kim, AY AF Onofrey, Shauna Aneja, Jasneet Haney, Gillian A. Nagami, Ellen H. DeMaria, Alfred Bowen, Melinda J. Cocoros, Noelle McGovern, Barbara H. Church, Daniel R. Kim, Arthur Y. TI Acute HCV in Massachusetts: Evidence of Systematic Underreporting to CDC SO HEPATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting and Postgraduate Course of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2013 CL Washington, DC SP Amer Assoc Study Liver Dis C1 [Onofrey, Shauna; Haney, Gillian A.; DeMaria, Alfred; Cocoros, Noelle; Church, Daniel R.] Massachusetts Dept Publ Hlth, Jamaica Plain, MA USA. [Aneja, Jasneet; Kim, Arthur Y.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Kim, Arthur Y.] Harvard Univ, Sch Med, Boston, MA USA. [Nagami, Ellen H.; DeMaria, Alfred] Harvard Ctr AIDS Res, Boston, MA USA. [Nagami, Ellen H.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Bowen, Melinda J.] Univ Massachusetts Correct Healthcare, Worcester, MA USA. [McGovern, Barbara H.] Tufts Med Sch, Boston, MA USA. [McGovern, Barbara H.] Abbvie Pharmaceut, N Chicago, IL 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 PD OCT PY 2013 VL 58 SU 1 SI SI MA 2270 BP 1306A EP 1306A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 297JR UT WOS:000330252206222 ER PT J AU Nambudiri, VE Bigby, ME AF Nambudiri, Vinod E. Bigby, Michael E. TI Risk of Malignant Disease and Biologic Response Modifiers Fact, Fiction, and Future Concerns SO JAMA DERMATOLOGY LA English DT Editorial Material ID TUMOR-NECROSIS-FACTOR; RHEUMATOID-ARTHRITIS; CANCER C1 [Nambudiri, Vinod E.; Bigby, Michael E.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Nambudiri, Vinod E.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Bigby, Michael E.] Beth Israel Deaconess Med Ctr, Dept Dermatol, Boston, MA 02215 USA. RP Nambudiri, VE (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 55 Fruit St,Bartlett Hall,Sixth Floor, Boston, MA 02114 USA. EM vnambudiri@partners.org NR 7 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD OCT PY 2013 VL 149 IS 10 BP 1221 EP 1223 DI 10.1001/jamadermatol.2013.5738 PG 3 WC Dermatology SC Dermatology GA AA3DT UT WOS:000330973800023 PM 23986262 ER PT J AU Chapman, LW Hsiao, JL Sarantopoulos, P Chiu, MW AF Chapman, Lance W. Hsiao, Jennifer L. Sarantopoulos, Peter Chiu, Melvin W. TI Reddish-Brown Nodules and Papules in an Elderly Man Progressive nodular histiocytosis SO JAMA DERMATOLOGY LA English DT Editorial Material C1 [Chapman, Lance W.; Hsiao, Jennifer L.; Chiu, Melvin W.] Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Los Angeles, CA 90095 USA. [Sarantopoulos, Peter] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Chiu, Melvin W.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Dermatol, Los Angeles, CA USA. RP Chiu, MW (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, 200 UCLA Med Plaza,Ste 450, Los Angeles, CA 90095 USA. EM mchiu@mednet.ucla.edu NR 9 TC 0 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD OCT PY 2013 VL 149 IS 10 BP 1229 EP 1230 DI 10.1001/jamadermatol.2013.4040 PG 2 WC Dermatology SC Dermatology GA AA3DT UT WOS:000330973800025 PM 23945611 ER PT J AU Munier, S Rolland, T Diot, C Jacob, Y Naffakh, N AF Munier, Sandie Rolland, Thomas Diot, Cedric Jacob, Yves Naffakh, Nadia TI Exploration of Binary Virus-Host Interactions Using an Infectious Protein Complementation Assay SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID INFLUENZA-A VIRUS; POLYMERASE COMPLEX; NUCLEAR IMPORT; MESSENGER-RNAS; NEUTRALIZING ANTIBODIES; LIFE-CYCLE; REPLICATION; SUBUNIT; H1N1; PB2 AB A precise mapping of pathogen-host interactions is essential for comprehensive understanding of the processes of infection and pathogenesis. The most frequently used techniques for interactomics are the yeast two-hybrid binary methodologies, which do not recapitulate the pathogen life cycle, and the tandem affinity purification mass spectrometry co-complex methodologies, which cannot distinguish direct from indirect interactions. New technologies are thus needed to improve the mapping of pathogen-host interactions. In the current study, we detected binary interactions between influenza A virus polymerase and host proteins during the course of an actual viral infection, using a new strategy based on trans-complementation of the Gluc1 and Gluc2 fragments of Gaussia princeps luciferase. Infectious recombinant influenza viruses that encode a Gluc1-tagged polymerase subunit were engineered to infect cultured cells transiently expressing a selected set of Gluc2-tagged cellular proteins involved in nucleocytoplasmic trafficking pathways. A random set and a literature-curated set of Gluc2-tagged cellular proteins were tested in parallel. Our assay allowed the sensitive and accurate recovery of previously described interactions, and it revealed 30% of positive, novel viral-host protein-protein interactions within the exploratory set. In addition to cellular proteins involved in the nuclear import pathway, components of the nuclear pore complex such as NUP62 and mRNA export factors such as NXF1, RMB15B, and DDX19B were identified for the first time as interactors of the viral polymerase. Gene silencing experiments further showed that NUP62 is required for efficient viral replication. Our findings give new insights regarding the subversion of host nucleocytoplasmic trafficking pathways by influenza A viruses. They also demonstrate the potential of our infectious protein complementation assay for high-throughput exploration of influenza virus interactomics in infected cells. With more infectious reverse genetics systems becoming available, this strategy should be widely applicable to numerous pathogens. C1 [Munier, Sandie; Diot, Cedric; Jacob, Yves; Naffakh, Nadia] Inst Pasteur, Unite Genet Mol Virus ARN, Dept Virol, F-75015 Paris, France. [Munier, Sandie; Diot, Cedric; Jacob, Yves; Naffakh, Nadia] CNRS, UMR3569, F-75015 Paris, France. [Munier, Sandie; Diot, Cedric; Jacob, Yves; Naffakh, Nadia] Univ Paris Diderot, Sorbonne Paris Cite, Unite Genet Mol Virus ARN, EA302, F-75015 Paris, France. [Rolland, Thomas; Jacob, Yves] Dana Farber Canc Inst, CCSB, Boston, MA 02215 USA. [Rolland, Thomas; Jacob, Yves] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Rolland, Thomas; Jacob, Yves] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Naffakh, N (reprint author), Inst Pasteur, Unite Genet Mol Virus ARN, Dept Virol, F-75015 Paris, France. EM yves_jacob@DFCI.HARVARD.edu; nadia.naffakh@pasteur.fr RI Munier, Sandie/F-6826-2016; OI Munier, Sandie/0000-0001-7819-128X; Naffakh, Nadia/0000-0002-0424-0277 FU Institut Pasteur (DARRI) [2010-790294]; European Commission [259751, 278433]; National Human Genome Research Institute [U01-HG001715, R01-HG006061] FX This work was funded by the Institut Pasteur (DARRI Project 2010-790294) and by the European Commission funded FP7 projects FLUPHARM (Grant Agreement No. 259751) and PREDEMICS (Grant Agreement No. 278433). Thomas Rolland was supported by Grant Nos. U01-HG001715 and R01-HG006061 from the National Human Genome Research Institute. NR 54 TC 16 Z9 16 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2013 VL 12 IS 10 BP 2845 EP 2855 DI 10.1074/mcp.M113.028688 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 301MS UT WOS:000330537000014 PM 23816991 ER PT J AU Heuer, HW Mirsky, JB Kong, EL Dickerson, BC Miller, BL Kramer, JH Boxer, AL AF Heuer, Hilary W. Mirsky, Jacob B. Kong, Erwin L. Dickerson, Bradford C. Miller, Bruce L. Kramer, Joel H. Boxer, Adam L. TI Antisaccade task reflects cortical involvement in mild cognitive impairment SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; EXECUTIVE FUNCTION; EYE-MOVEMENTS; DEMENTIA; SCHIZOPHRENIA; INDIVIDUALS; DEGENERATION; PERFORMANCE; COMMUNITY; DECLINE AB Objective: The aims of this study were to examine executive dysfunction using an antisaccade (AS) task in normal elderly (NE) and patients with mild cognitive impairment (MCI) and Alzheimer disease (AD) as well as to evaluate the relationship between AS performance and cortical thinning within AD-associated regions. Methods: We recorded eye movements in 182 subjects (NE: 118; MCI: 36; AD: 28) during an AS task. We also performed neuropsychological measures of executive function for comparison. Brain MRI scans were collected on most subjects, and cortical thickness was determined in 9 regions known to exhibit atrophy in AD dementia ("AD signature"). We investigated the relationships between AS and neuropsychological performance, as well as possible correlations between AS performance and cortical thickness. Results: AS performance in MCI resembled that in NE; subjects with AD were impaired relative to both MCI and NE. In all subjects, AS performance correlated with neuropsychological measures of executive function, even after controlling for disease severity. In the subjects with MCI but not in NE, cortical thickness in frontoparietal AD signature regions correlated with AS performance. Conclusions: The AS task is a useful measure of executive function across the AD spectrum. In MCI, AS performance may reflect disease burden within cortical brain regions involved in oculomotor control; however, AS impairments in NE may have etiologies other than incipient AD. C1 [Heuer, Hilary W.; Mirsky, Jacob B.; Kong, Erwin L.; Miller, Bruce L.; Kramer, Joel H.; Boxer, Adam L.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Frontotemporal Disorders Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Heuer, HW (reprint author), Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA. EM hheuer@memory.ucsf.edu FU NIH [R01AG031278, R01AG038791, R01AG032289]; Hellman Family Foundation; John Douglas French Foundation; Silicon Valley Foundation; Tau Research Consortium; Larry L. Hillblom Foundation; NIH National Institute on Aging [P01AG019724, P50AG023501] FX Supported in part by NIH grants R01AG031278 and R01AG038791 to Dr. Boxer, as well as the Hellman Family Foundation, the John Douglas French Foundation, the Silicon Valley Foundation, and the Tau Research Consortium. Dr. Kramer was supported by NIH grant R01AG032289 and the Larry L. Hillblom Foundation. Dr. Dickerson's contribution was supported in part by AGP50-AG005134 and the Alzheimer's Association. The project described was supported by grant numbers P01AG019724 and P50AG023501 from NIH National Institute on Aging. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institute on Aging or the NIH. NR 31 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD OCT 1 PY 2013 VL 81 IS 14 BP 1235 EP 1243 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AA0EN UT WOS:000330768200013 PM 23986300 ER PT J AU Quesnel, AM Moonis, G Appel, J O'Malley, JT Curtin, HD McKenna, MJ AF Quesnel, Alicia Marie Moonis, Gul Appel, Jason O'Malley, Jennifer T. Curtin, Hugh D. McKenna, Michael J. TI IN RESPONSE TO LETTER TO THE EDITOR: "CORRELATION OF COMPUTED TOMOGRAPHY WITH HISTOPATHOLOGY IN OTOSLCEROSIS", QUESNEL ET AL. OTOL NEUROTOL 2013; 34(1):22-8 SO OTOLOGY & NEUROTOLOGY LA English DT Letter ID SPIRAL LIGAMENT; OTOSCLEROSIS C1 [Quesnel, Alicia Marie; O'Malley, Jennifer T.; McKenna, Michael J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Quesnel, Alicia Marie; O'Malley, Jennifer T.; McKenna, Michael J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Moonis, Gul; Appel, Jason; Curtin, Hugh D.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Moonis, Gul] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. RP Quesnel, AM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD OCT PY 2013 VL 34 IS 8 BP 1546 EP 1547 PG 3 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 301HO UT WOS:000330523600037 PM 24026031 ER PT J AU Basu, S Andrews, J AF Basu, Sanjay Andrews, Jason TI Complexity in Mathematical Models of Public Health Policies: A Guide for Consumers of Models SO PLOS MEDICINE LA English DT Review ID TRANSMISSION MODEL; CHOLERA EPIDEMIC; HIV PREVENTION; INFECTION; HAITI; COMPUTATION; INFERENCE; SELECTION; DYNAMICS; STRATEGY C1 [Basu, Sanjay] Stanford Univ, Prevent Res Ctr, Stanford, CA 94305 USA. [Basu, Sanjay] Stanford Univ, Ctr Hlth Policy Primary Care & Outcomes Res, Stanford, CA 94305 USA. [Basu, Sanjay] Stanford Univ, Ctr Poverty & Inequal, Stanford, CA 94305 USA. [Basu, Sanjay] London Sch Hyg & Trop Med, Dept Publ Hlth & Policy, London WC1, England. [Andrews, Jason] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Andrews, Jason] Harvard Univ, Sch Med, Boston, MA USA. RP Basu, S (reprint author), Stanford Univ, Prevent Res Ctr, Stanford, CA 94305 USA. EM basus@stanford.edu RI Barley, Kamal/F-9579-2011; OI Barley, Kamal/0000-0003-1874-9813; Andrews, Jason/0000-0002-5967-251X NR 29 TC 19 Z9 19 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD OCT PY 2013 VL 10 IS 10 AR e1001540 DI 10.1371/journal.pmed.1001540 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 299BU UT WOS:000330370600020 PM 24204214 ER PT J AU Matthews, LT Kaida, A Kanters, S Byakwagamd, H Mocello, AR Muzoora, C Kembabazi, A Haberer, JE Martin, JN Bangsberg, DR Hunt, PW AF Matthews, Lynn T. Kaida, Angela Kanters, Steven Byakwagamd, Helen Mocello, A. Rain Muzoora, Conrad Kembabazi, Annet Haberer, Jessica E. Martin, Jeffrey N. Bangsberg, David R. Hunt, Peter W. TI HIV-infected women on antiretroviral treatment have increased mortality during pregnant and postpartum periods SO AIDS LA English DT Article DE Africa; antiretroviral therapy; HIV; immune reconstitution; maternal health; maternal mortality; mortality; postpartum; pregnancy; women ID MATERNAL MORTALITY; SOUTH-AFRICA; REPRODUCTIVE INTENTIONS; POSITIVE WOMEN; FOLLOW-UP; THERAPY; UGANDA; CHILD; PREVENTION; ZIMBABWE AB Objective: To assess the impact of pregnancy on mortality among HIV-infected Ugandan women initiating ART. Design: Prospective cohort study. Methods: HIV-infected women initiating ART in the Uganda AIDS Rural Treatment Outcomes study were assessed quarterly for self-reported pregnancy. The association between pregnancy and postpartum ('pregnancy-related') follow-up periods and mortality was assessed with Cox proportional hazards models adjusted for age, CD4 cell count, plasma HIV-1 RNA levels, and ART duration. Results: Three hundred and fifty-four women with median age 33 years (IQR: 27-37) and CD4 142 cells/ml (IQR: 82-213) were followed for a median of 4.0 years (IQR: 2.5-4.8) after ART initiation, with 3 and 7% loss-to-follow-up at years 1 and 5. One hundred and nine women experienced pregnancy. Five deaths occurred during pregnancy-related follow-up and 16 during nonpregnancy-related follow-up, for crude mortality rates during the first year after ART initiation of 12.57/100 PYs and 3.53/100 PYs (rate ratio 3.56, 95% CI: 0.97-11.07). In adjusted models, the impact of pregnancy-related follow-up on mortality was highest at ART initiation (aHR: 21.48, 95% CI: 3.73-123.51), decreasing to 13.44 (95% CI 3.28-55.11) after 4 months, 8.28 (95% CI 2.38-28.88) after 8 months, 5.18 (95% CI: 1.36-19.71) after 1 year, and 1.25 (95% CI: 0.10-15.58) after 2 years on ART. Four of five maternal deaths occurred postpartum. Conclusion: Pregnancy and the postpartum period were associated with increased mortality in HIV-infected women initiating ART, particularly during early ART. Contraception proximate to ART initiation, earlier ART initiation, and careful monitoring during the postpartum period may reduce maternal mortality in this setting. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Matthews, Lynn T.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Div Infect Dis, Boston, MA 02114 USA. [Matthews, Lynn T.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Kaida, Angela] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Byakwagamd, Helen; Mocello, A. Rain; Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Kanters, Steven] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada. [Byakwagamd, Helen; Muzoora, Conrad; Kembabazi, Annet; Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Haberer, Jessica E.] Massachusetts Gen Hosp, Ctr Global Hlth, Dept Med, Boston, MA 02114 USA. [Martin, Jeffrey N.; Hunt, Peter W.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Matthews, LT (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM ltmatthews@partners.org FU Sullivan Family Foundation; Doris Duke Clinical Scientist Development Award [2008047]; [MH54907]; [AI100765]; [HD069194]; [NIAID P30 027763]; [NIMH 095655]; [087228]; [NIMH 87227] FX This project was supported by R01 (Bangsberg MH54907), R56 (Hunt AI100765), R21 (Kaida HD069194), NIAID P30 027763 funds, and The Sullivan Family Foundation. Lynn Matthews and Jessica Haberer are supported by K23 awards (NIMH 095655 and 087228). David Bangsberg is supported by a K24 award (NIMH 87227). Peter Hunt is supported by Doris Duke Clinical Scientist Development Award (2008047). The content of this manuscript is the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 45 TC 8 Z9 8 U1 0 U2 4 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 OCT PY 2013 VL 27 SU 1 BP S105 EP S112 DI 10.1097/QAD.0000000000000040 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 298UD UT WOS:000330349100012 PM 24088676 ER PT J AU Ajayi, T Richter, J Campbell, E Namias, J AF Ajayi, Tokunbo Richter, James Campbell, Emily Namias, Joshua TI Quality of Colonoscopy Prep in Inpatients versus Outpatients at a Community-based Hospital SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Ajayi, Tokunbo; Namias, Joshua] Salem Hosp, Salem, MA USA. [Richter, James; Campbell, Emily] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 1991 BP S605 EP S605 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178102321 ER PT J AU Alishahi, Y Kundrotas, L AF Alishahi, Yasmin Kundrotas, Leon TI A Retrospective Review of the Clinical Impact of Hydrogen Breath Testing for Small Bowel Bacterial Overgrowth in South Texas Veterans Health Care System SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Alishahi, Yasmin] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Kundrotas, Leon] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 1643 BP S493 EP S493 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178101795 ER PT J AU Anderson, J Goel, G Cohen, H Leung, F AF Anderson, Joshua Goel, Gati Cohen, Hartley Leung, Felix TI Water Infusion Distension during Colonoscopy Is a Safe Alternative Technique to Facilitate Polypectomy in a "Difficult Location" SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Anderson, Joshua; Goel, Gati; Cohen, Hartley; Leung, Felix] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 1484 BP S440 EP S440 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178101636 ER PT J AU Basu, P Shah, N Siriki, R Rahaman, M Farhat, S AF Basu, Patrick Shah, Niraj Siriki, Ravi Rahaman, Md Farhat, S. TI Romiplostim's Effect to Optimize SVR with Telaprevir, Ribavirin, and PEG Interferon-alfa 2a in Thrombocytopenic Cirrhotics with Chronic Hepatitis C: A Placebo-controlled Prospective Clinical Trial: RESTRAINT C Trial SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Basu, Patrick; Farhat, S.] Columbia Sch Physicians & Surg, New York, NY USA. [Siriki, Ravi; Rahaman, Md] NSLIJHS Hofstra N Shore LIJ Sch Med, New York, NY USA. [Shah, Niraj] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 506 BP S150 EP S150 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178100506 ER PT J AU Basu, P Shah, N Siriki, R Rahaman, M Farhat, S AF Basu, Patrick Shah, Niraj Siriki, Ravi Rahaman, Md Farhat, S. TI Telaprevir with Adjusted Dose of Ribavirin in Naive CHC-G1: Efficacy and Treatment in CHC in Hemodialysis Population TARGET C Trial: A Placebo Randomized Control Clinical Trial SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Basu, Patrick; Farhat, S.] Columbia Sch Phys & Surg, New York, NY USA. [Siriki, Ravi; Rahaman, Md] NSLIJHS Hofstra N Shore LIJ Sch Med, New York, NY USA. [Shah, Niraj] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 513 BP S152 EP S152 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178100513 ER PT J AU Basu, P Shah, N Siriki, R Rahaman, M Farhat, S AF Basu, Patrick Shah, Niraj Siriki, Ravi Rahaman, Md Farhat, S. TI Curcumin, Antioxidant, and Pioglitazone Therapy with Inclusion of Vitamin E In Non-Alcoholic Fatty Liver Disease: A Randomized, Open-label, Placebo-controlled Clinical Prospective Trial (CAPTIVE) SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Basu, Patrick; Farhat, S.] Columbia Sch Phys & Surg, New York, NY USA. [Siriki, Ravi; Rahaman, Md] NSLIJHS Hofstra North Shore LIJ Sch Med, New York, NY USA. [Shah, Niraj] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 505 BP S149 EP S150 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178100505 ER PT J AU Basu, P Shah, N Rahaman, M Siriki, R Farhat, S AF Basu, Patrick Shah, Niraj Rahaman, Md Siriki, Ravi Farhat, S. TI Prevalence of Small Bowel Bacterial Overgrowth (SIBO) in Decompensated Cirrhosis with Portal Hypertension: A Clinical Pilot Study SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Basu, Patrick; Farhat, S.] Columbia Sch Phys & Surg, New York, NY USA. [Rahaman, Md; Siriki, Ravi] NSLIJHS Hofstra North Shore LIJ Sch Med, New York, NY USA. [Shah, Niraj] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 486 BP S144 EP S145 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178100486 ER PT J AU Basu, P Shah, N Farhat, S Siriki, R Rahaman, M AF Basu, Patrick Shah, Niraj Farhat, S. Siriki, Ravi Rahaman, Md TI Restless Leg Syndrome (RLS) is Associated with Hepatic Encephalopathy (HE) in Decompensated Cirrhosis: A Clinical Pilot Study SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Basu, Patrick; Farhat, S.] Columbia Sch Phys & Surg, New York, NY USA. [Siriki, Ravi; Rahaman, Md] NSLIJHS Hofstra North Shore LIJ Sch Med, New York, NY USA. [Shah, Niraj] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 485 BP S144 EP S144 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178100485 ER PT J AU Basu, P Shah, N Siriki, R Rahaman, M Farhat, S AF Basu, Patrick Shah, Niraj Siriki, Ravi Rahaman, Md Farhat, S. TI Effect of N Acetylcysteine (NAC) in Hypoxia-Induced Liver Injury (HILI): A Randomized Placebo Control Clinical Trial SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Basu, Patrick; Farhat, S.] Columbia Sch Phys & Surg, New York, NY USA. [Siriki, Ravi; Rahaman, Md] NSLIJHS Hofstra North Shore LIJ Sch Med, New York, NY USA. [Shah, Niraj] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 484 BP S144 EP S144 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178100484 ER PT J AU Basu, P Shah, N Rahaman, MD Siriki, R Farhat, S AF Basu, Patrick Shah, Niraj Rahaman, M. D. Siriki, Ravi Farhat, S. TI Rifabutin, Omeprazole, Alinia, and Doxycycline Therapy for Prior Treatment Failure Helicobacter pylori Population: A Randomized, Open-Label Clinical Pilot Study ROAD Trial SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Basu, Patrick; Farhat, S.] Columbia Sch Phys & Surg, New York, NY USA. [Rahaman, M. D.; Siriki, Ravi] NSLIJHS Hofstra North Shore LIJ Sch Med, New York, NY USA. [Shah, Niraj] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, New York, NY USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 157 BP S49 EP S49 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178100158 ER PT J AU Basu, P Shah, N Siriki, R Rahaman, MD Farhat, S AF Basu, Patrick Shah, Niraj Siriki, Ravi Rahaman, M. D. Farhat, S. TI Latent Eosinophilic Esophagitis (LEOE) Is a Unraveled Novel Clinical Entity: A Randomized, Open Clinical Pilot Study SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Basu, Patrick; Farhat, S.] Columbia Sch Phys & Surg, New York, NY USA. [Siriki, Ravi; Rahaman, M. D.] NSLIJHS Hofstra North Shore LIJ Sch Med, New York, NY USA. [Shah, Niraj] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 68 BP S23 EP S24 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178100069 ER PT J AU Blackshear, L Aranda-Michel, E Wolfsen, H Wallace, M Tearney, G AF Blackshear, Leslie Aranda-Michel, Edgar Wolfsen, Herbert Wallace, Michael Tearney, Gary TI Volumetric Laser Endomicroscopy (VLE): An OFDI Case Study of Barrett's Esophagus with Dysplasia SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Blackshear, Leslie; Aranda-Michel, Edgar; Wolfsen, Herbert; Wallace, Michael] Mayo Clin Florida, Jacksonville, FL USA. [Tearney, Gary] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 3 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 2163 BP S656 EP S656 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178102489 ER PT J AU Chen, XH Lu, L Xu, H Sears, P Kelly, C AF Chen, Xinhua Lu, Lei Xu, Hua Sears, Pam Kelly, Ciaran TI Steroid Therapy Exacerbates Clostridium difficile Infection in a Mouse Model SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Chen, Xinhua; Lu, Lei; Xu, Hua; Kelly, Ciaran] Harvard Univ, Sch Med, BIDMC, Div Gastroenterol, Boston, MA USA. [Sears, Pam] Optimer Pharmaceut Inc, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 1820 BP S549 EP S549 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178102151 ER PT J AU Clifford, D McAuliffe, M Stephens, K Major, E Fox, I Milch, C Sankoh, S Provenzale, J Lev, M Freedland, E Berger, J Parikh, A AF Clifford, David McAuliffe, Megan Stephens, Kristin Major, Eugene Fox, Irving Milch, Catherine Sankoh, Serap Provenzale, James Lev, Michael Freedland, Eric Berger, Joseph Parikh, Asit TI Risk Assessment and Minimization for Progressive Multifocal Leukoencephalopathy (PML RAMP): A Program to Assess for Potential Early Signs and Symptoms of PML during Clinical Development of Vedolizumab SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Clifford, David] Washington Univ, Sch Med, St Louis, MO USA. [McAuliffe, Megan; Stephens, Kristin; Fox, Irving; Sankoh, Serap; Freedland, Eric] Millennium Pharmaceut Inc, Cambridge, MA USA. [Major, Eugene] NINDS, NIH, Bethesda, MD 20892 USA. [Milch, Catherine; Provenzale, James] Duke Univ, Med Ctr, Durham, NC USA. [Lev, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Berger, Joseph] Univ Kentucky, Lexington, KY USA. [Parikh, Asit] Takeda Pharmaceut Int Inc, Deerfield, IL USA. NR 0 TC 3 Z9 3 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 1673 BP S502 EP S502 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178102007 ER PT J AU Hotte, C Vela, M AF Hotte, Charles Vela, Marcelo TI Body Mass Index (BMI) and Percent Fat Are Not Associated with Increased Reflux in a Veteran Hospital Review SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Hotte, Charles] Baylor Coll Med, Houston, TX 77030 USA. [Vela, Marcelo] Michael E Debakey Vet Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 38 BP S14 EP S14 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178100039 ER PT J AU Ihunnah, C Khoruts, A Fischer, M Afzali, A Aroniadis, O Barto, A Borody, T Brandt, L Giovanelli, A Gordon, S Hohmann, E Kao, DN Kao, J McQuillen, D Mellow, M Rank, K Ray, A Schwartz, M Singh, N Stollman, N Surawicz, C Suskind, D Vindigni, S Youngster, I Kelly, C AF Ihunnah, Chioma Khoruts, Alexander Fischer, Monika Afzali, Anita Aroniadis, Olga Barto, Amy Borody, Thomas Brandt, Lawrence Giovanelli, Andrea Gordon, Shelley Hohmann, Elizabeth Kao, Dina Kao, John McQuillen, Daniel Mellow, Mark Rank, Kevin Ray, Arnab Schwartz, Margot Singh, Namita Stollman, Neil Surawicz, Christina Suskind, David Vindigni, Stephen Youngster, Ilan Kelly, Colleen TI Fecal Microbiota Transplantation (FMT) for Treatment of Clostridium difficile Infection (CDI) in Immunocompromised Patients SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Ihunnah, Chioma; Kelly, Colleen] Brown Alpert Med Sch, Providence, RI USA. [Hohmann, Elizabeth; Youngster, Ilan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fischer, Monika] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Kao, John] Univ Michigan, Ann Arbor, MI 48109 USA. [Singh, Namita; Suskind, David] Seattle Childrens Hosp, Seattle, WA USA. [Aroniadis, Olga; Brandt, Lawrence] Montefiore Med Ctr, Bronx, NY 10467 USA. [Mellow, Mark] INTEGRIS Baptist Med Ctr, Oklahoma City, OK USA. [Ray, Arnab] Ochsner Clin Fdn, New Orleans, LA USA. [Barto, Amy; McQuillen, Daniel] Lahey Clin Med Ctr, Burlington, MA 01803 USA. [Khoruts, Alexander; Rank, Kevin] Univ Minnesota, Minneapolis, MN USA. [Giovanelli, Andrea; Stollman, Neil] Northern Calif Gastroenterol Consultants Inc, Oakland, CA USA. [Gordon, Shelley] Calif Pacific Med Ctr, San Francisco, CA USA. [Kao, Dina] Univ Alberta, Edmonton, AB, Canada. [Schwartz, Margot] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Borody, Thomas] Ctr Digest Dis, Sydney, NSW, Australia. [Afzali, Anita; Surawicz, Christina; Vindigni, Stephen] Univ Washington, Sch Med, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 611 BP S179 EP S180 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178100611 ER PT J AU Kaung, A Chak, E Cohen, H Ohning, G Leung, F AF Kaung, Aung Chak, Eric Cohen, Hartley Ohning, Gordon Leung, Felix TI Water Exchange Colonoscopy without Air Insufflation May Facilitate Terminal Ileum Intubation SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Kaung, Aung; Cohen, Hartley; Ohning, Gordon; Leung, Felix] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. [Chak, Eric] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 1483 BP S439 EP S440 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178101635 ER PT J AU Konijeti, G Khalili, H Ananthakrishnan, A Higuchi, L Fuchs, C Richter, J Chan, A AF Konijeti, Gauree Khalili, Hamed Ananthakrishnan, Ashwin Higuchi, Leslie Fuchs, Charles Richter, James Chan, Andrew TI Does Parental Age Influence the Risk of Inflammatory Bowel Disease in Offspring? SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Konijeti, Gauree; Khalili, Hamed; Ananthakrishnan, Ashwin; Richter, James; Chan, Andrew] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Higuchi, Leslie] Childrens Hosp, Div Gastroenterol & Nutr, Boston, MA 02115 USA. [Fuchs, Charles] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 1814 BP S547 EP S547 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178102146 ER PT J AU Konijeti, G Sauk, J Shrime, M Ananthakrishnan, A AF Konijeti, Gauree Sauk, Jenny Shrime, Mark Ananthakrishnan, Ashwin TI Cost-effectiveness of Competing Strategies for Recurrent Clostridium difficile Infection ACG/AstraZeneca Fellow Award SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Konijeti, Gauree; Sauk, Jenny; Ananthakrishnan, Ashwin] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Shrime, Mark] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 1579 BP S473 EP S473 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178101731 ER PT J AU Korant, A Shaik, M Saha, S Gay, G Saha, S AF Korant, Alpesh Shaik, Mohammed Saha, Supriya Gay, Greer Saha, Sukamal TI Tumor Size Predicts Long-Term Survival in Colon Cancer Patients: Analysis of National Cancer Database (NCDB) SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Korant, Alpesh; Saha, Sukamal] McLaren Flint Med Ctr, Flint, MI USA. [Shaik, Mohammed] Hurley Med Ctr, Flint, MI USA. [Saha, Supriya] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gay, Greer] Amer Coll Surg Commiss Canc, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 550 BP S162 EP S162 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178100550 ER PT J AU Kovacs, T Jensen, D Ohning, G Ghassemi, K Dulai, G Machicado, G Jutabha, R AF Kovacs, Thomas Jensen, Dennis Ohning, Gordon Ghassemi, Kevin Dulai, Gareth Machicado, Gustavo Jutabha, Rome TI A Prospective Study of Patients with Bleeding Mallory Weiss Tears: Does Portal Hypertension Matter? SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Ghassemi, Kevin; Jutabha, Rome] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Dulai, Gareth] CURE DDRC GI Hemostasis Res Unit, Los Angeles, CA USA. [Ohning, Gordon] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Kovacs, Thomas; Jensen, Dennis; Machicado, Gustavo] Univ Calif Los Angeles, Div Digest Dis, Los Angeles, CA USA. [Kovacs, Thomas; Jensen, Dennis; Machicado, Gustavo] VA WLA Med Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 2029 BP S615 EP S615 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178102357 ER PT J AU Lopez, J Konijeti, G Nguyen, D Sauk, J Yajnik, V Ananthakrishnan, A AF Lopez, Joanna Konijeti, Gauree Nguyen, Deanna Sauk, Jenny Yajnik, Vijay Ananthakrishnan, Ashwin TI Natural History of Crohn's Disease Following Permanent Ileostomy: Implications for Endoscopic Surveillance SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Lopez, Joanna; Konijeti, Gauree; Nguyen, Deanna; Sauk, Jenny; Yajnik, Vijay; Ananthakrishnan, Ashwin] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 1695 BP S510 EP S510 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178102029 ER PT J AU Mahmood, S Campbell, E Richter, J AF Mahmood, Syed Campbell, Emily Richter, James TI Non-bleeding Indications for Inpatient Colonoscopy SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Mahmood, Syed] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Campbell, Emily; Richter, James] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 2041 BP S619 EP S619 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178102369 ER PT J AU Mahmood, S Campbell, E Richter, J AF Mahmood, Syed Campbell, Emily Richter, James TI Frequency and Cost of Repeating Inpatient Colonoscopy Secondary to Suboptimal Bowel Preparation SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Mahmood, Syed] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Campbell, Emily; Richter, James] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 1970 BP S599 EP S599 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178102300 ER PT J AU Mahmood, S Campbell, E Richter, J AF Mahmood, Syed Campbell, Emily Richter, James TI Mid-afternoon versus Evening Start Time for Polyethylene Glycol Preparation in Hospitalized Patients Undergoing Next Day Colonoscopy SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Mahmood, Syed] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Campbell, Emily; Richter, James] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 1928 BP S583 EP S584 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178102258 ER PT J AU McPhaul, C Sonnenberg, A Genta, R AF McPhaul, Christopher Sonnenberg, Amnon Genta, Robert TI Low Prevalence of Colon Polyps in Patients with Diarrhea and Microscopic Colitis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Genta, Robert] Miraca Life Sci Res Inst, GI Pathol, Irving, TX USA. [McPhaul, Christopher] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR USA. [Sonnenberg, Amnon] OHSU, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 558 BP S164 EP S164 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178100558 ER PT J AU Mehrzad, R Leung, J Alejos, A Hundal, N Katz, A Yuan, Q Hesterberg, P Shreffler, W AF Mehrzad, Raman Leung, John Alejos, Alexandra Hundal, Navneet Katz, Aubrey Yuan, Qian Hesterberg, Paul Shreffler, Wayne TI Serial Diagnostic EGDs Used to Identify Food Trigger(s) in Eosinophilic Esophagitis Are Safe SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Mehrzad, Raman; Leung, John; Alejos, Alexandra; Hesterberg, Paul; Shreffler, Wayne] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA USA. [Hundal, Navneet; Katz, Aubrey; Yuan, Qian] Harvard Univ, Sch Med, Massachusetts Gen Hosp Children, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 65 BP S23 EP S23 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178100066 ER PT J AU Nguyen, K Jacobs, J Cao, WW Chak, E Cohen, H Leung, F AF Nguyen, Ken Jacobs, Jonathan Cao, Weiwei Chak, Eric Cohen, Hartley Leung, Felix TI Water Exchange Colonoscopy for Evaluation of Severe Ulcerative Colitis: A Case Series SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Cohen, Hartley; Leung, Felix] VA Greater Los Angeles Healthcare Syst, Div Gastroenterol, Los Angeles, CA USA. [Nguyen, Ken] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. [Jacobs, Jonathan; Cao, Weiwei; Chak, Eric] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 1405 BP S416 EP S417 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178101557 ER PT J AU Raza, MQ Trang, T Qureshi, W AF Raza, Mohammad Qasim Trang, Tony Qureshi, Waqar TI Colo-colonic Intussusception Presenting as Intermittent Testicular Pain SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Raza, Mohammad Qasim; Qureshi, Waqar] Baylor Coll Med, Houston, TX 77030 USA. [Trang, Tony] VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 1324 BP S394 EP S394 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178101476 ER PT J AU Scoville, E Konijeti, G Yajnik, V Nguyen, D Sauk, J Ananthakrishnan, A AF Scoville, Elizabeth Konijeti, Gauree Yajnik, Vijay Nguyen, Deanna Sauk, Jenny Ananthakrishnan, Ashwin TI Preventability of Venous Thromboembolism in Patients with Inflammatory Bowel Disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Scoville, Elizabeth; Konijeti, Gauree; Yajnik, Vijay; Nguyen, Deanna; Sauk, Jenny; Ananthakrishnan, Ashwin] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 1700 BP S511 EP S512 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178102034 ER PT J AU Sharma, A Smith, D AF Sharma, Anurag Smith, David TI Autoimmune Hemolytic Anemia: A Part of the Hematological Spectrum of Celiac Disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Sharma, Anurag] Mt Sinai Sch Med, St Josephs Reg Med Ctr Program, Paterson, NJ USA. [Smith, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Hematol & Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 954 BP S285 EP S285 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178101106 ER PT J AU Sonnenberg, A Byrd-Clark, D AF Sonnenberg, Amnon Byrd-Clark, Danita TI US Hospitalizations for Colorectal Cancer: 1970-2010 SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Sonnenberg, Amnon] Portland VA Med Ctr, GI P3, Portland, OR USA. [Byrd-Clark, Danita] Social & Sci Syst, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 557 BP S164 EP S164 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178100557 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Time Trends of US Hospitalization for Esophageal Disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 13 BP S5 EP S5 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178100014 ER PT J AU Taydas, E Malik, M Russell, S Latt, N Gurakar, A AF Taydas, Eren Malik, Mohammad Russell, Stuart Latt, Nyan Gurakar, Ahmet TI The Role of Coronary Artery Calcium Score and Age in Early Identification of Occult Coronary Artery Disease among Patients Undergoing Liver Transplant Work-up for End-stage Liver Disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Taydas, Eren] MedStar Franklin Sq Med Ctr, Baltimore, MD USA. [Malik, Mohammad; Russell, Stuart; Gurakar, Ahmet] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Latt, Nyan] W Los Angeles Vet Affairs Med Ctr, Dept Gastroenterol & Hepatol, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 500 BP S148 EP S148 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178100500 ER PT J AU Wang, MH Fiocchi, C Zhu, XF Ripke, S Kamboh, I Rebert, N Duerr, R Achkar, JP AF Wang, Ming-Hsi Fiocchi, Claudio Zhu, Xiaofeng Ripke, Stephan Kamboh, Ilyas Rebert, Nancy Duerr, Richard Achkar, Jean-Paul TI Novel Gene-Gene and Gene-Environment Interactions in Ulcerative Colitis ACG IBD Research Award SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 78th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 11-16, 2013 CL San Diego, CA SP Amer Coll Gastroenterol C1 [Wang, Ming-Hsi; Fiocchi, Claudio; Rebert, Nancy; Achkar, Jean-Paul] Cleveland Clin, Inst Digest Dis, Cleveland, OH 44106 USA. [Zhu, Xiaofeng] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Ripke, Stephan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kamboh, Ilyas; Duerr, Richard] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 1690 BP S508 EP S508 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178102024 ER PT J AU Maust, DT Oslin, DW Thase, ME AF Maust, Donovan T. Oslin, David W. Thase, Michael E. TI Going Beyond Antidepressant Monotherapy for Incomplete Response in Nonpsychotic Late-Life Depression: A Critical Review SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Review DE Antidepressant; augmentation; depression; pharmacotherapy ID TREATMENT-RESISTANT DEPRESSION; RECURRENT MAJOR DEPRESSION; LITHIUM AUGMENTATION; GERIATRIC DEPRESSION; PRIMARY-CARE; REFRACTORY DEPRESSION; UNIPOLAR DEPRESSION; ELDERLY-PATIENTS; CONTROLLED-TRIAL; OLDER PATIENTS AB Many older adults with major depressive disorder (MDD) do not respond to antidepressant monotherapy. Although there are evidence-based treatment options to support treatment beyond monotherapy for adults, the evidence for such strategies, specifically in late-life MDD, is relatively scarce. This review examines the published data describing strategies for antidepressant augmentation or acceleration studied specifically in older adults, including lithium, stimulants, and second-generation antipsychotics. In addition, the authors suggest strategies for future research, such as study of specific agents, refining understanding of the impact of medical or cognitive comorbidity in late-life depression, and comparative effectiveness to examine methods already used in clinical practice. C1 [Maust, Donovan T.; Oslin, David W.; Thase, Michael E.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Oslin, David W.; Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Oslin, David W.; Thase, Michael E.] VISN 4 Mental Illness Res Educ & Clin Ctr MIREC, Philadelphia, PA USA. [Thase, Michael E.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. RP Maust, DT (reprint author), Univ Penn, Sect Geriatr Psychiat, 3615 Chestnut St, Philadelphia, PA 19104 USA. EM Donovan.Maust@uphs.upenn.edu FU NIMH [R25-MH060490] FX Dr. Maust is supported through the NIMH-funded Clinical Research Scholars Program (R25-MH060490) of the Department of Psychiatry, University of Pennsylvania, Perelman School of Medicine. NR 58 TC 10 Z9 10 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD OCT PY 2013 VL 21 IS 10 BP 973 EP 986 DI 10.1016/j.jagp.2013.01.030 PG 14 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 298YZ UT WOS:000330362300007 PM 23567381 ER PT J AU Liang, WY Chang, WC Hsu, CY Arnason, T Berger, D Hawkins, AT Sylla, P Lauwers, GY AF Liang, Wen-Yih Chang, Wei-Chin Hsu, Chih-Yi Arnason, Thomas Berger, David Hawkins, Alexander T. Sylla, Patricia Lauwers, Gregory Y. TI Retrospective Evaluation of Elastic Stain in the Assessment of Serosal Invasion of pT3N0 Colorectal Cancers SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE colorectal cancer; elastic stain; elastic lamina invasion; peritoneal involvement; CK7 ID COLON-CANCER; PERITONEAL INVOLVEMENT; 7TH EDITION; HIGH-RISK; CARCINOMA; CLASSIFICATION; CATEGORIZATION; SURVIVAL; OUTCOMES; LAMINA AB Peritoneal involvement is an important adverse prognostic factor in colorectal cancer (CRC) and determines a shift in the pathologic tumor node metastasis stage. Because peritoneal involvement is difficult to identify, use of special stains highlighting the peritoneal elastic lamina and mesothelial surface has been proposed. This study aims to determine whether use of elastic stain or CK7 immunohistochemistry on a single tissue section can refine the level of tumor invasion and determine whether restaging based on this assessment has prognostic significance in pT3N0 CRCs. Elastic stains were applied to 1 block per case from 244 consecutively resected pT3N0M0 CRCs. CK7 was evaluated in a 169-case subset. The elastic lamina was identified in only 101 cases (41%). Of those, 60 cases (24.6%) displayed elastic lamina invasion (ELI). This finding was associated with significantly worse (P < 0.001) disease-free survival (DFS) (5-y DFS = 60%) and significantly worse (P = 0.01) overall survival (OS) (5-y OS = 66.7%) compared with patients with no ELI (5-y DFS = 87.8%, OS = 92.7%) and those for whom no elastic lamina was identified (5-y DFS= 82.5%, OS = 86.0%). CK7 staining highlighted mesothelial cells in only 27 of 169 cases tested and helped demonstrate serosal invasion in only 5 cases (3%). In summary, the use of a single elastic stain is a useful and inexpensive method to demonstrate peritoneal involvement by tumor and should be considered for routine use in all pT3N0 CRCs. As tumors with ELI have an adverse prognosis, we propose that they should be upstaged compared with pT3N0 tumors without ELI. C1 [Liang, Wen-Yih; Chang, Wei-Chin; Hsu, Chih-Yi] Taipei Vet Gen Hosp, Dept Pathol & Lab Med, Taipei 112, Taiwan. [Liang, Wen-Yih; Chang, Wei-Chin; Hsu, Chih-Yi] Natl Yang Ming Univ, Dept Pathol, Sch Med, Taipei, Taiwan. [Liang, Wen-Yih; Arnason, Thomas; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. [Berger, David; Hawkins, Alexander T.; Sylla, Patricia] Massachusetts Gen Hosp, Dept Surg, Div Gastrointestinal Surg, Boston, MA 02114 USA. [Berger, David; Hawkins, Alexander T.; Sylla, Patricia] Harvard Univ, Sch Med, Boston, MA USA. RP Liang, WY (reprint author), Taipei Vet Gen Hosp, Dept Pathol, 201,Sec 2,Shi Pai Rd, Taipei 112, Taiwan. EM wyliang@vghtpe.gov.tw FU Royal College of Physicians and Surgeons of Canada (Detweiler Traveling Fellowship); Dalhousie University (McLoughlin Scholarship); NIH NHLBI T32 Harvard/Longwood Vascular Surgery Training Program [HL007734] FX T.A.'s fellowship funding was provided through scholarships from the Royal College of Physicians and Surgeons of Canada (Detweiler Traveling Fellowship) and Dalhousie University (McLoughlin Scholarship). Dr Hawkins is supported by the NIH NHLBI T32 (HL007734) Harvard/Longwood Vascular Surgery Training Program. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 20 TC 8 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 2013 VL 37 IS 10 BP 1565 EP 1570 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 299YB UT WOS:000330430500010 PM 23774172 ER PT J AU Mason, EF Sadow, PM Wagner, AJ Remillard, SP Flood, TA Belanger, EC Hornick, JL Barletta, JA AF Mason, Emily F. Sadow, Peter M. Wagner, Andrew J. Remillard, Stephen P. Flood, Trevor A. Belanger, Eric C. Hornick, Jason L. Barletta, Justine A. TI Identification of Succinate Dehydrogenase-deficient Bladder Paragangliomas SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE bladder paragangliomas; succinate dehydrogenase; immunohistochemistry ID GASTROINTESTINAL STROMAL TUMORS; CARNEY-STRATAKIS-SYNDROME; RENAL-CELL CARCINOMA; SDHD GENE-MUTATIONS; GERM-LINE MUTATIONS; COMPLEX-II GENE; MALIGNANT PHEOCHROMOCYTOMAS; FAMILIAL PHEOCHROMOCYTOMA; CLINICAL-IMPLICATIONS; PULMONARY CHONDROMA AB A significant number of patients with paragangliomas harbor germline mutations in one of the succinate dehydrogenase (SDH) genes (SDHA, B, C, or D). Tumors with mutations in SDH genes can be identified using immunohistochemistry. Loss of SDHB staining is seen in tumors with a mutation in any one of the SDH genes, whereas loss of both SDHB and SDHA expression is seen only in the context of an SDHA mutation. Identifying an SDH-deficient tumor can be prognostically significant, as tumors with SDHB mutations are more likely to pursue a malignant course. Although the rate of SDH deficiency in paragangliomas in general is known to be approximately 30%, there are only rare reports of SDH-deficient bladder paragangliomas. Therefore, the aim of this study was to determine the rate of SDH deficiency in bladder paragangliomas. Eleven cases of bladder paragangliomas were identified. Hematoxylin and eosin-stained slides of all tumors were reviewed, and immunohistochemical analysis for SDHB and SDHA was performed. For cases with loss of SDHA expression by immunohistochemistry, mutation analysis of the SDHA gene was performed. Loss of SDHB staining was seen in 3 (27%) cases (2 with loss of SDHB only, 1 with loss of SDHB and SDHA). Patients with SDH-deficient tumors were younger than those with tumors with intact SDH expression (mean age at presentation 39 y and 58 y, respectively). Of the 2 patients with SDHB-deficient and SDHA-intact tumors, one was found to have a germline SDHB mutation, and the other had a family history of a malignant paraganglioma. Both patients developed metastatic disease. The one patient with a tumor that was deficient for both SDHB and SDHA had no family history of paragangliomas and no evidence of metastatic disease. Sequencing of this tumor revealed a deleterious heterozygous single-base pair substitution in exon 10 of SDHA (c. 1340 A > G; p.His447Arg) in both the tumor and normal tissue, indicative of a germline SDHA mutation, and a deleterious singlebase pair substitution in exon 5 of SDHA (c. 484 A > T; p.Arg162*) in 1 allele of the tumor only. No patients with intact SDH expression had a family history of paragangliomas; 1 had a synchronous paraganglioma, but none developed metastatic disease. A significant subset of bladder paragangliomas is SDH deficient. It is essential to identify SDH-deficient tumors, as the presence of an SDH mutation has prognostic implications and is important in guiding genetic counseling. C1 [Mason, Emily F.; Hornick, Jason L.; Barletta, Justine A.] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Sadow, Peter M.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wagner, Andrew J.; Remillard, Stephen P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Flood, Trevor A.; Belanger, Eric C.] Ottawa Hosp, Dept Pathol, Ottawa, ON, Canada. RP Barletta, JA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM jbarletta@partners.org OI Flood, Trevor/0000-0002-5227-2708 NR 36 TC 3 Z9 3 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 2013 VL 37 IS 10 BP 1612 EP 1618 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 299YB UT WOS:000330430500016 PM 23797725 ER PT J AU Wanderer, JP Anderson-Dam, J AF Wanderer, Jonathan P. Anderson-Dam, John TI ANESTHESIA INFORMATION MANAGEMENT SYSTEM RECORDS AND OPERATIVE NOTES: A COMPARISON OF ESTIMATED BLOOD LOSS SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Technology-in-Anesthesia (STA) CY JAN 09-12, 2013 CL Scottsdale, AZ SP Soc Technol Anesthesia, Int Anesthesia Res Soc, Soc Cardiovascular Anesthesiologists, Soc Pediat Anesthesia, Soc Ambulatory Anesthesia, Int Soc Anaesthet Pharmacol, Anesthesia Patient Safety Fdn, Soc Crit Care Anesthesiologists, Soc Obstet Anesthesia & Perinatol C1 [Wanderer, Jonathan P.] Vanderbilt Univ, Dept Anesthesia, Nashville, TN 37235 USA. [Anderson-Dam, John] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD OCT PY 2013 VL 117 SU 1 BP 72 EP 73 PG 2 WC Anesthesiology SC Anesthesiology GA 300CZ UT WOS:000330443300037 ER PT J AU Yuki, K Bu, WM Xi, J Shimaoka, M Eckenhoff, R AF Yuki, Koichi Bu, Weiming Xi, Jin Shimaoka, Motomu Eckenhoff, Roderic TI Propofol Shares the Binding Site with Isoflurane and Sevoflurane on Leukocyte Function-Associated Antigen-1 SO ANESTHESIA AND ANALGESIA LA English DT Article ID HUMAN SERUM-ALBUMIN; GENERAL-ANESTHETICS; I-DOMAIN; INTEGRIN LFA-1; CARDIOPULMONARY BYPASS; INFLAMMATORY RESPONSE; CRYSTAL-STRUCTURES; RECEPTOR FUNCTION; GABA(A) RECEPTOR; STRUCTURAL BASIS AB BACKGROUND: We previously demonstrated that propofol interacted with the leukocyte adhesion molecule leukocyte function-associated antigen-1 (LFA-1) and inhibited the production of interleukin-2 via LFA-1 in a dependent manner. However, the binding site(s) of propofol on LFA-1 remains unknown. METHODS: First, the inhibition of LFA-1's ligand binding by propofol was confirmed in an enzyme-linked immunosorbent assay (ELISA) ELISA-type assay. The binding site of propofol on LFA-1 was probed with a photolabeling experiment using a photoactivatable propofol analog called azi-propofol-m. The adducted residues of LFA-1 by this compound were determined using liquid chromatography-mass spectrometry. In addition, the binding of propofol to the ligand-binding domain of LFA-1 was examined using 1-aminoanthracene (1-AMA) displacement assay. Furthermore, the binding site(s) of 1-AMA and propofol on LFA-1 was studied using the docking program GLIDE. RESULTS: We demonstrated that propofol impaired the binding of LFA-1 to its ligand intercellular adhesion molecule-1. The photolabeling experiment demonstrated that the adducted residues were localized in the allosteric cavity of the ligand-binding domain of LFA-1 called "lovastatin site." The shift of fluorescence spectra was observed when 1-AMA was coincubated with the low-affinity conformer of LFA-1 ligand-binding domain (wild-type [WT] alpha L I domain), not with the high-affinity conformer, suggesting that 1-AMA bound only to WT alpha L I domain. In the 1-AMA displacement assay, propofol decreased 1-AMA fluorescence signal (at 520 nm), suggesting that propofol competed with 1-AMA and bound to the WT alpha L I domain. The docking simulation demonstrated that both 1-AMA and propofol bound to the lovastatin site, which agreed with the photolabeling experiment. CONCLUSIONS: We demonstrated that propofol bound to the lovastatin site in LFA-1. Previously we showed that the volatile anesthetics isoflurane and sevoflurane bound to this site. Taken together, the lovastatin site is an example of the common binding sites for anesthetics currently used clinically. C1 [Yuki, Koichi; Shimaoka, Motomu] Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Yuki, Koichi; Shimaoka, Motomu] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Yuki, Koichi; Shimaoka, Motomu] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. [Bu, Weiming; Xi, Jin; Eckenhoff, Roderic] Univ Penn, Dept Anesthesiol & Crit Care, Perelman Sch Med, Philadelphia, PA 19104 USA. [Shimaoka, Motomu] Mie Univ, Dept Mol Pathobiol & Cell Adhes Biol, Grad Sch Med, Tsu, Mie 514, Japan. RP Yuki, K (reprint author), Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, 300 Longwood Ave, Boston, MA 02115 USA. EM yuki.koichi@gmail.com FU National Institutes of Health (NIH) [P01GM55876, K08GM101345]; CHMC Anesthesia Foundation FX Funding: This work is in part supported by National Institutes of Health (NIH) grants P01GM55876 (RE), K08GM101345 (KY), and CHMC Anesthesia Foundation (KY). NR 55 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD OCT PY 2013 VL 117 IS 4 BP 803 EP 811 DI 10.1213/ANE.0b013e3182a00ae0 PG 9 WC Anesthesiology SC Anesthesiology GA 299ZU UT WOS:000330435000009 PM 23960033 ER PT J AU Bauer, ME Bateman, BT Bauer, ST Shanks, AM Mhyre, JM AF Bauer, Melissa E. Bateman, Brian T. Bauer, Samuel T. Shanks, Amy M. Mhyre, Jill M. TI Maternal Sepsis Mortality and Morbidity During Hospitalization for Delivery: Temporal Trends and Independent Associations for Severe Sepsis SO ANESTHESIA AND ANALGESIA LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; UNITED-STATES; SEPTIC SHOCK; MULTIPLE PREGNANCIES; CESAREAN DELIVERY; EPIDEMIOLOGY; INFECTIONS; CARE; NETHERLANDS; GUIDELINES AB BACKGROUND: Sepsis is currently the leading cause of direct maternal death in the United Kingdom. In this study, we aimed to determine frequency, temporal trends, and independent associations for severe sepsis during hospitalization for delivery in the United States. METHODS: Data were obtained from the Nationwide Inpatient Sample for the years 1998 through 2008. The presence of severe sepsis was identified by the appropriate International Classification of Diseases, Ninth Revision, Clinical Modification codes. Logistic regression analysis was used to assess temporal trends for sepsis, severe sepsis, and sepsis-related death and also to identify independent associations of severe sepsis. RESULTS: Of an estimated 44,999,260 hospitalizations for delivery, sepsis complicated 1: 3333 (95% confidence interval [CI], 1: 3151-1: 3540) deliveries, severe sepsis complicated 1: 10,823 (95% CI, 1: 10,000-1: 11,792) deliveries, and sepsis-related death complicated 1: 105,263 (95% CI, 1: 83,333-1: 131,579) deliveries. While the overall frequency of sepsis was stable (P = 0.95), the risk of severe sepsis and sepsis-related death increased during the study period, (P < 0.001) and (P = 0.02), respectively. Independent associations for severe sepsis, with an adjusted odds ratio and lower bound 95% CI higher than 3, include congestive heart failure, chronic liver disease, chronic renal disease, systemic lupus erythematous, and rescue cerclage placement. CONCLUSIONS: Maternal severe sepsis and sepsis-related deaths are increasing in the United States. Severe sepsis often occurs in the absence of a recognized risk factor and underscores the need for developing systems of care that increase sensitivity for disease detection across the entire population. Physicians should enhance surveillance in patients with congestive heart failure, chronic liver disease, chronic renal disease, and systemic lupus erythematous and institute early treatment when signs of sepsis are emerging. C1 [Bauer, Melissa E.; Mhyre, Jill M.] Univ Michigan Hlth Syst, Dept Anesthesiol, Div Obstet Anesthesia, Ann Arbor, MI 48109 USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Bateman, Brian T.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Bateman, Brian T.] Harvard Univ, Sch Med, Boston, MA USA. [Bauer, Samuel T.] Oakland Univ, William Beaumont Sch Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, Royal Oak, MI USA. Univ Michigan Hlth Syst, Dept Anesthesiol, Ann Arbor, MI 48109 USA. RP Bauer, ME (reprint author), Univ Michigan Hlth Syst, Dept Anesthesiol, Neurosci Hosp L3622, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM mbalun@med.umich.edu FU University of Michigan Department of Anesthesiology FX Funding: This study was funded by University of Michigan Department of Anesthesiology. NR 30 TC 29 Z9 30 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD OCT PY 2013 VL 117 IS 4 BP 944 EP 950 DI 10.1213/ANE.0b013e3182a009c3 PG 7 WC Anesthesiology SC Anesthesiology GA 299ZU UT WOS:000330435000024 PM 24023020 ER PT J AU Gordon, CR Swanson, EW Susarla, SM Coon, D Rada, E Al Rakan, M Santiago, GF Shores, JT Bonawitz, SC Fishman, EK Murphy, R Armand, M Liacouras, P Grant, GT Brandacher, G Lee, WPA AF Gordon, Chad R. Swanson, Edward W. Susarla, Srinivas M. Coon, Devin Rada, Erin Al Rakan, Mohammed Santiago, Gabriel F. Shores, Jaimie T. Bonawitz, Steven C. Fishman, Elliot K. Murphy, Ryan Armand, Mehran Liacouras, Peter Grant, Gerald T. Brandacher, Gerald Lee, Wei-Ping Andrew TI Overcoming Cross-Gender Differences and Challenges in Le Fort-Based, Craniomaxillofacial Transplantation With Enhanced Computer-Assisted Technology SO ANNALS OF PLASTIC SURGERY LA English DT Article; Proceedings Paper CT 3rd Biennial Meeting of the American-Society-for-Reconstructive-Transplantation CY NOV, 2012 CL Chicago, IL SP Amer Soc Reconstruct Transplantat DE face transplant; craniomaxillofacial; vascularized composite allotransplantation (VCA); sex; cross-gender; intraoperative cutting guide ID DONOR GENDER; ALLOTRANSPLANTATION; CYTOMEGALOVIRUS; RECOMMENDATIONS; SURVIVAL; PROTOCOL; MODEL; FACE AB Background: Sex-specific anthropometrics, skin texture/adnexae mismatch, and social apprehension have prevented cross-gender facial transplantation from evolving. However, the scarce donor pool and extreme waitlist times are currently suboptimal. Our objective was to (1) perform and assess cadaveric facial transplantation for each sex-mismatched scenario using virtual planning with cutting guide fabrication and (2) review the advantages/disadvantages of cross-gender facial transplantation. Methods: Cross-gender facial transplantation feasibility was evaluated through 2 mock, double-jaw, Le Fort-based cadaveric allotransplants, including female donor-to-male recipient and male donor-to-female recipient. Hybrid facial-skeletal relationships were investigated using cephalometric measurements, including sellion-nasion-A point and sellion-nasion-B point angles, and lower-anterior-facial-height to total-anterior-facial-height ratio. Donor and recipient cutting guides were designed with virtual planning based on our team's experience in swine dissections and used to optimize the results. Results: Skeletal proportions and facial-aesthetic harmony of the transplants (n = 2) were found to be equivalent to all reported experimental/clinical sex-matched cases by using custom guides and Mimics technology. Cephalometric measurements relative to Eastman Normal Values are shown. Conclusions: On the basis of our results, we believe that cross-gender facial transplantation can offer equivalent, anatomical skeletal outcomes to those of sex-matched pairs using preoperative planning and custom guides for execution. Lack of literature discussion of cross-gender facial transplantation highlights the general stigmata encompassing the subject. We hypothesize that concerns over sex-specific anthropometrics, skin texture/adnexae disparity, and increased immunological resistance have prevented full acceptance thus far. Advantages include an increased donor pool with expedited reconstruction, as well as size-matched donors. C1 [Gordon, Chad R.; Swanson, Edward W.; Susarla, Srinivas M.; Coon, Devin; Rada, Erin; Al Rakan, Mohammed; Santiago, Gabriel F.; Shores, Jaimie T.; Bonawitz, Steven C.; Brandacher, Gerald; Lee, Wei-Ping Andrew] Johns Hopkins Univ, Sch Med, Johns Hopkins Hosp, Dept Plast & Reconstruct Surg, Baltimore, MD 21287 USA. [Susarla, Srinivas M.] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Fishman, Elliot K.] Johns Hopkins Univ, Sch Med, Johns Hopkins Hosp, Dept Radiol, Baltimore, MD 21287 USA. [Murphy, Ryan; Armand, Mehran] Johns Hopkins Univ, Appl Phys Lab, Laurel, MD USA. [Liacouras, Peter; Grant, Gerald T.] Walter Reed Natl Mil Med Ctr, Med Applicat Ctr 3D, Dept Radiol, Bethesda, MD USA. RP Gordon, CR (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Hosp, Dept Plast & Reconstruct Surg, JHOC 8161,601 N Caroline St, Baltimore, MD 21287 USA. EM cgordon@jhmi.edu RI Brandacher, Gerald/L-7540-2016; OI Murphy, Ryan/0000-0003-3065-7700; fishman, elliot/0000-0002-2567-1658; Susarla, Srinivas/0000-0003-0155-8260 FU NCATS NIH HHS [UL1 TR000424, UL1TR000424-06] NR 15 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 EI 1536-3708 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD OCT PY 2013 VL 71 IS 4 BP 421 EP 428 DI 10.1097/SAP.0b013e3182a0df45 PG 8 WC Surgery SC Surgery GA 300GX UT WOS:000330453500023 PM 24025655 ER PT J AU Conrad, MF Kang, J Mukhopadhyay, S Patel, VI LaMuraglia, GM Cambria, RP AF Conrad, Mark F. Kang, Jeanwan Mukhopadhyay, Shankha Patel, Virendra I. LaMuraglia, Glenn M. Cambria, Richard P. TI A Risk Prediction Model for Determining Appropriateness of CEA in Patients with Asymptomatic Carotid Artery Stenosis SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 133rd Annual Meeting of the American-Surgical-Association (ASA) CY APR 04-06, 2013 CL Indianapolis, IN SP Amer Surg Assoc DE asymptomatic carotid; carotid artery; carotid endarterectomy; risk prediction; stroke ID STROKE PREVENTION; VASCULAR-SURGERY; ENDARTERECTOMY; TRIAL; OCTOGENARIANS; METAANALYSIS; MANAGEMENT; SURVIVAL; EFFICACY; OUTCOMES AB Objective: The benefit of carotid endarterectomy (CEA) overmedical therapy in patients with asymptomatic carotid artery stenosis is predicated upon a life expectancy of at least 5 years after the procedure. The goal of this study was to create a scoring system for prediction of 5-year survival after CEA that can be used to triage patients with ACAS. Methods: All patients who underwent CEA for severe asymptomatic carotid stenosis from 1989 to 2005 were identified. Long-term survival was determined by a review of hospital records and the social security death index. Because all patients had at least 5-year follow-up, a logistic regression of predictors of survival at 5 years was performed and the odds ratios associated with particular significant comorbidities were used to create a scoring system to predict survival. The scoring system was then validated within the cohort using the Hosmer-Lemeshow Test and a derivation/validation receiver operating characteristic (ROC) curve. Results: There were 2004 CEA performed in 1791 patients. The average follow-upwas 130 +/- 49 months. The clinical profile of the cohort data included 84% hypertension, 56% coronary artery disease (CAD), 24% diabetes, and 71% on statins. The 30-day stroke rate was 1.1% and the death rate was 0.7%. The actual 5-year survival was 73%. Logistic regression yielded the following predictors of mortality: age (by decade) (odds ratio [OR] = 1.8, P < 0.0001), CAD(OR = 1.5, P = 0.0007), chronic obstructive pulmonary disease (OR = 2.5; P < 0.0001), diabetes (OR = 1.7, P < 0.0001), neck radiation (OR = 2.6, P = 0.005), no statin (OR = 2.1, P < 0.0001), and creatinine more than 1.5 (OR = 2.6, P < 0.0001). These variables were then assigned a hierarchal point scoring system in accordance with the OR value. The 5-year survival based on the scoring system was as follows: 0 to 5 points = 92.5%, 6 to 8 points = 83.6%, 9 to 11 points = 63.7%, 12 to 14 points = 46.5%, and more than 15 points = 33.8%. The Hosmer-Lemeshow test validated the scoring system (P = 0.26) and there was no difference in the ROC curves (C statistic = 0.74 vs 0.73). Conclusions: This validated scoring system can be a useful tool for determining which patients are likely to benefit most from CEA based on the probability of long-term survival. Given that the 5-year survival of patients in the medical arm of the asymptomatic CEA trials was 60% to 70%, it is reasonable to conclude that patients who score 0 to 8 points are excellent candidates for CEA whereas most patients with >= 12 points should be managed with medical therapy alone. C1 [Conrad, Mark F.; Kang, Jeanwan; Mukhopadhyay, Shankha; Patel, Virendra I.; LaMuraglia, Glenn M.; Cambria, Richard P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Conrad, MF (reprint author), Massachusetts Gen Hosp, 55 Fruit St,WAC 440, Boston, MA 02114 USA. EM mconrad@partners.org NR 31 TC 8 Z9 8 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD OCT PY 2013 VL 258 IS 4 BP 534 EP 540 DI 10.1097/SLA.0b013e3182a5007b PG 7 WC Surgery SC Surgery GA 300LB UT WOS:000330464300003 PM 23979268 ER PT J AU Creutzberg, CL Kitchener, HC Birrer, MJ Landoni, F Lu, KH Powell, M Aghajanian, C Edmondson, R Goodfellow, PJ Quinn, M Salvesen, HB Thomas, G AF Creutzberg, Carien L. Kitchener, Henry C. Birrer, Michael J. Landoni, Fabio Lu, Karen H. Powell, Melanie Aghajanian, Carol Edmondson, Richard Goodfellow, Paul J. Quinn, Michael Salvesen, Helga B. Thomas, Gillian CA Second GCIG Endometrial Canc TI Gynecologic Cancer InterGroup (GCIG) Endometrial Cancer Clinical Trials Planning Meeting Taking Endometrial Cancer Trials Into the Translational Era SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Endometrial cancer; Randomised trials; Clinical trials planning meeting; International collaboration; Gynecological Cancer Intergroup ID OVARIAN-CANCER; ONCOLOGY-GROUP; CHEMOTHERAPY; RADIOTHERAPY; CARCINOMA; METAANALYSIS AB Objective: The second Gynecologic Cancer InterGroup (GCIG) Endometrial Cancer Clinical Trials Planning Meeting was held on December 1, 2012, and included international multidisciplinary representatives of the 24 member groups. The aims were to review recent advances in molecular pathology of endometrial cancer, focusing on molecular-based therapy, and to identify key hypotheses and issues to be addressed through international collaborative clinical trials. Methods: Reviews and summaries of current knowledge were presented followed by parallel working group sessions for surgery, adjuvant and systemic therapy, and translational research. Plenary discussions were held to integrate translational and clinical issues, and a final discussion session to agree on key trial concepts. Results and Conclusions: Proposals to take forward on the following trials were agreed: (1) lymphadenectomy to direct adjuvant treatment in women with high-risk endometrial cancer, including a sentinel node substudy; (2) conservative therapy for low-risk endometrial cancers in morbidly obese women with high surgical risks and for fertility-sparing treatment in premenopausal patients; (3) adjuvant therapy for women with early-stage carcinosarcoma. A proposal was made that a GCIG Early Phase Consortium be developed to serve as an international platform for rapid assessment of biomarkers. C1 [Creutzberg, Carien L.; Second GCIG Endometrial Canc] Leiden Univ, Med Ctr, Dept Clin Oncol, NL-2300 RC Leiden, Netherlands. [Kitchener, Henry C.] Univ Manchester, Inst Canc Sci, Manchester M13 9PL, Lancs, England. [Birrer, Michael J.] Harvard Univ, Sch Med, Div Hematol & Oncol, Boston, MA USA. [Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Landoni, Fabio] European Inst Oncol, Div Gynaecol, Milan, Italy. [Lu, Karen H.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. [Powell, Melanie] Barts Hlth NHS Trust, Dept Clin Oncol, London, England. [Aghajanian, Carol] Mem Sloan Kettering Canc Ctr, Dept Med Oncol, New York, NY 10021 USA. [Edmondson, Richard] Newcastle Univ, Dept Gynaecol, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Edmondson, Richard] Northern Inst Canc Res, Newcastle Upon Tyne, Tyne & Wear, England. [Goodfellow, Paul J.] Ohio State Univ, Coll Med, Dept Obstet & Gynecol, Columbus, OH 43210 USA. [Quinn, Michael] Royal Womens Hosp, Dept Gynaecol Oncol, Melbourne, Vic, Australia. [Quinn, Michael] Univ Melbourne, Dept Obstet & Gynaecol, Melbourne, Vic 3010, Australia. [Salvesen, Helga B.] Haukeland Hosp, Dept Obstet & Gynecol, Bergen, Norway. [Salvesen, Helga B.] Univ Bergen, Dept Clin Med, N-5020 Bergen, Norway. [Thomas, Gillian] Sunnybrook Canc Ctr, Dept Radiat Oncol, Toronto, ON, Canada. RP Creutzberg, CL (reprint author), Leiden Univ, Med Ctr, Dept Clin Oncol, Postzone K1-P,Albinusdreef 2,POB 9600, NL-2300 RC Leiden, Netherlands. EM c.l.creutzberg@lumc.nl RI Miller, David/H-4604-2011; Mahner, Sven/F-3560-2014; Piovano, Elisa/J-6846-2016; Lorusso, Domenica/K-6523-2016; salvesen, Helga/C-1187-2017; OI Quinn, Michael/0000-0003-0694-3870; Miller, David/0000-0002-8215-5887; Piovano, Elisa/0000-0002-5629-703X; Lorusso, Domenica/0000-0003-0981-0598; salvesen, Helga/0000-0002-4438-8831; Glasspool, Rosalind/0000-0002-5000-1680 FU Gynecological Cancer InterGroup; National Cancer Institute, USA; Leiden University Fund-van Walsum; Nucletron BV FX The GCIG Endometrial Cancer Clinical Trials Planning meeting was funded by unrestricted grants from the Gynecological Cancer InterGroup (www.gcig.igcs.org); the National Cancer Institute, USA; Leiden University Fund-van Walsum; and Nucletron BV. NR 21 TC 3 Z9 3 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X EI 1525-1438 J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD OCT PY 2013 VL 23 IS 8 BP 1528 EP 1534 DI 10.1097/IGC.0b013e3182a26edb PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 299CY UT WOS:000330373900030 PM 24257568 ER PT J AU Chan, J Brady, M Penson, R Monk, B Boente, M Walker, J Davidson, S DiSilvestro, P O'Malley, D Morgan, M Pearl, M De Geest, K Michael, H AF Chan, J. Brady, M. Penson, R. Monk, B. Boente, M. Walker, J. Davidson, S. DiSilvestro, P. O'Malley, D. Morgan, M. Pearl, M. De Geest, K. Michael, H. TI PHASE III TRIAL OF EVERY-3-WEEKS PACLITAXEL VS. DOSE DENSE WEEKLY PACLITAXEL WITH CARBOPLATIN plus /- BEVACIZUMAB IN EPITHELIAL OVARIAN, PERITONEAL, FALLOPIAN TUBE CANCER: GOG 262 (NCT01167712) SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Meeting Abstract C1 [Chan, J.] UCSF Helen Diller Family Comprehens Canc Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, San Francisco, CA USA. [Brady, M.] Stat & Data Ctr, Gynecol Oncol Grp, Buffalo, NY USA. [Penson, R.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Monk, B.] Creighton Univ, Sch Med, Dept Obstet & Gynecol, Phoenix, AZ USA. [Boente, M.] Metrominnesota CCOP, Dept Hematol Oncol, Edina, MN USA. [Walker, J.] Univ Oklahoma, Dept Obstet & Gynecol, Norman, OK 73019 USA. [Davidson, S.] Univ Colorado, Ctr Canc, Anschutz Ctr Adv Med Fitzsimons, Dept Obstet & Gynecol, Aurora, CO USA. [DiSilvestro, P.] Brown Univ, Women & Infants Hosp, Dept Obstet & Gynecol, Providence, RI USA. [O'Malley, D.] Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. [Morgan, M.] Fox Chase Canc Ctr, Dept Surg Oncol, Gynecol Oncol Sect, Philadelphia, PA 19111 USA. [Pearl, M.] Stony Brook Univ Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Stony Brook, NY USA. [De Geest, K.] Univ Iowa, Dept Obstet & Gynecol, Iowa City, IA 52242 USA. [Michael, H.] Indiana Univ, Ctr Canc, Clarian North Med Ctr, Dept Pathol, Carmel, IN USA. RI OMalley, David/E-3789-2011 NR 0 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X EI 1525-1438 J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD OCT PY 2013 VL 23 IS 8 SU 1 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 299EW UT WOS:000330379500008 ER PT J AU Kristeleit, R Burris, H LoRusso, P Patel, M Giordano, H Isaacson, J Borrow, J Allen, A Jaw-Tsai, S Shapiro, G AF Kristeleit, R. Burris, H., III LoRusso, P. Patel, M. Giordano, H. Isaacson, J. Borrow, J. Allen, A. Jaw-Tsai, S. Shapiro, G. TI PHASE 1 STUDY OF CONTINUOUS ORAL RUCAPARIB: ANALYSIS OF PATIENT SUBGROUP WITH OVARIAN/PERITONEAL CANCER SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Meeting Abstract C1 [Kristeleit, R.] UCL, Inst Canc, London, England. [Burris, H., III] Sarah Cannon Res Inst, Nashville, TN USA. [LoRusso, P.] Karmanos Canc Inst, Detroit, MI USA. [Patel, M.] Florida Canc Specialists, Sarah Cannon Res Inst, Sarasota, FL USA. [Giordano, H.; Borrow, J.; Allen, A.; Jaw-Tsai, S.] Clovis Oncol Inc, San Francisco, CA USA. [Isaacson, J.] Clovis Oncol Inc, Boulder, CO USA. [Shapiro, G.] Dana Farber Canc Inst, Ctr Early Drug Dev, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X EI 1525-1438 J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD OCT PY 2013 VL 23 IS 8 SU 1 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 299EW UT WOS:000330379501235 ER PT J AU Minion, L Tewari, KS Chan, JK Penson, RT Cohn, DE Monk, BJ AF Minion, L. Tewari, K. S. Chan, J. K. Penson, R. T. Cohn, D. E. Monk, B. J. TI A TRIAL-BASED ECONOMIC ASSESSMENT OF BEVACIZUAMB AND CHEMOTHERAPY VERSUS CHEMOTHERAPY ALONE FOR ADVANCED CERVICAL CANCER: COST-EFFECTIVE ANALYSIS OF GYNECOLOGIC ONCOLOGY GROUP (GOG) PROTOCOL 240 SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Meeting Abstract C1 [Minion, L.] St Josephs Hosp, Phoenix, AZ USA. [Tewari, K. S.] Univ Calif Irvine, Med Ctr, Div Gynecol Oncol, Orange, CA USA. [Chan, J. K.] Univ Calif San Francisco, Div Gynecol Oncol, San Francisco, CA 94143 USA. [Penson, R. T.] Massachusetts Gen Hosp, Dept Med Hematol & Oncol, Boston, MA 02114 USA. [Cohn, D. E.] Ohio State Univ, Div Gynecol Oncol, Columbus, OH 43210 USA. [Monk, B. J.] Creighton Univ, Sch Med, Div Gynecol Oncol, Phoenix, AZ USA. [Monk, B. J.] Univ Arizona, Ctr Canc, St Josephs Hosp, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X EI 1525-1438 J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD OCT PY 2013 VL 23 IS 8 SU 1 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 299EW UT WOS:000330379500209 ER PT J AU Philpott, S Rizzuto, I Fraser, L Manchanda, R Hadwin, R Burnell, M Mackay, S Skates, S Menon, U Jacobs, I Rosenthal, A AF Philpott, S. Rizzuto, I. Fraser, L. Manchanda, R. Hadwin, R. Burnell, M. Mackay, S. Skates, S. Menon, U. Jacobs, I. Rosenthal, A. TI DETECTION OF NON-OVARIAN CANCERS ON PHASE 2 OF THE UK FAMILIAL OVARIAN CANCER SCREENING STUDY (UKFOCSS) SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Meeting Abstract C1 [Philpott, S.; Rizzuto, I.; Fraser, L.; Manchanda, R.; Hadwin, R.; Burnell, M.; Mackay, S.; Menon, U.] UCL, London, England. [Skates, S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Skates, S.] Harvard Univ, Sch Med, Boston, MA USA. [Jacobs, I.] Univ Manchester, Manchester, Lancs, England. [Rosenthal, A.] Queen Mary Univ London, Barts & London Sch Med & Dent, London, England. NR 0 TC 0 Z9 0 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X EI 1525-1438 J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD OCT PY 2013 VL 23 IS 8 SU 1 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 299EW UT WOS:000330379501264 ER PT J AU Kanyago, S Riding, DM Mutakooha, E de la O, AL Siedner, MJ AF Kanyago, Samuel Riding, David M. Mutakooha, Elichum de la O, Alcides Lopez Siedner, Mark J. TI Shang Ring Versus Forceps-Guided Adult Male Circumcision: A Randomized, Controlled Effectiveness Study in Southwestern Uganda SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV/AIDS; Uganda; sub-Saharan Africa; adult male circumcision; HIV prevention; acceptability; feasibility ID HIV PREVENTION; TRIAL; MEN; INTERVENTION; DEVICE; RAKAI AB Adult male circumcision (AMC) reduces HIV transmission, but uptake is limited in part by current surgical methods. We randomized HIV-uninfected men (n = 138) to receive Shang Ring (SR)- or forceps-guided AMC from a locally trained surgeon. In as-treated analyses, more SR procedures were completed within 10 minutes (79% versus 0%, P < 0.01) and more subjects reported high satisfaction (77% versus 58%, P = 0.03). Healing time and pain scores were similar, though minor complication rates were higher in SR subjects (56% versus 24%, P < 0.01). SR circumcision is a rapid and acceptable method of AMC and should be further evaluated to increase uptake of AMC. C1 [Kanyago, Samuel; Mutakooha, Elichum; de la O, Alcides Lopez; Siedner, Mark J.] Mbarara Univ Sci & Technol, Fac Med, Dept Surg, Mbarara, Uganda. [Kanyago, Samuel] Good Shepherd Hosp, Siteki, Swaziland. [Riding, David M.] North West Deanery, Manchester, Lancs, England. [Riding, David M.] Mbarara Reg Referral Hosp, Mbarara, Uganda. [Siedner, Mark J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Global Hlth, Boston, MA USA. RP Kanyago, S (reprint author), Good Shepherd Hosp, 3 Km,Siteki Maphungwane Rd, Siteki, Swaziland. EM kanyagosamuel@gmail.com FU Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University [R24 TW007988]; NIH [T32 AI007433] FX M.J.S. received salary support from the Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University (R24 TW007988), and NIH (T32 AI007433). NR 15 TC 6 Z9 12 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD OCT 1 PY 2013 VL 64 IS 2 BP 130 EP 133 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 300GP UT WOS:000330452700008 PM 23599013 ER PT J AU Kanyago, S Riding, DM Siedner, MJ AF Kanyago, Samuel Riding, David M. Siedner, Mark J. TI Authors' Reply: Proper Surgical Training and Grading of Complications for Shang Ring Circumcision Are Necessary SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter C1 [Kanyago, Samuel] Mbarara Univ Sci & Technol, Fac Med, Dept Surg, Mbarara, Uganda. [Kanyago, Samuel] Good Shepherd Hosp, Dept Surg, Siteki, Swaziland. [Riding, David M.] North West Deanery, Manchester, Lancs, England. [Siedner, Mark J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Siedner, Mark J.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Siedner, Mark J.] Harvard Univ, Sch Med, Boston, MA USA. RP Kanyago, S (reprint author), Mbarara Univ Sci & Technol, Fac Med, Dept Surg, Mbarara, Uganda. FU FIC NIH HHS [R24 TW007988]; NIAID NIH HHS [T32 AI007433]; NIMH NIH HHS [K23 MH099916] NR 4 TC 0 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD OCT 1 PY 2013 VL 64 IS 2 BP E12 EP E12 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 300GP UT WOS:000330452700002 PM 24043119 ER PT J AU Mackay, DD Huesmann, GR Wu, RI Stone, JR Pless, ML AF Mackay, Devin D. Huesmann, Graham R. Wu, Roseann I. Stone, James R. Pless, Misha L. TI Giant Cell Arteritis Causing Symmetric Bilateral Posterior Circulation Infarcts SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article DE giant cell arteritis; stroke; posterior circulation; temporal arteritis ID VERTEBRAL ARTERY; ISCHEMIC COMPLICATIONS; TEMPORAL ARTERITIS; OCCLUSION; DIAGNOSIS; DISEASE AB An 82-year-old woman presented with bilateral, symmetric posterior circulation infarctions secondary to giant cell arteritis (GCA). Her atypical clinical presentation included a lack of headache and fever, but she exhibited signs of systemic illness including generalized weakness, cachexia, apathy, and anemia. Laboratory testing revealed a markedly elevated erythrocyte sedimentation rate, but only a borderline elevated C-reactive protein. Head and neck vascular imaging demonstrated a pattern of vertebral arterial narrowing consistent with GCA-a diagnosis confirmed by temporal artery biopsy. Her unusual symptomatic, laboratory, and imaging presentation highlights the importance of considering GCA in the differential diagnosis of unusual bilateral stroke syndromes, where early treatment decreases morbid outcomes. C1 [Mackay, Devin D.; Huesmann, Graham R.; Pless, Misha L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 01945 USA. [Wu, Roseann I.; Stone, James R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 01945 USA. [Pless, Misha L.] Harvard Univ, Sch Med, Boston, MA USA. RP Pless, ML (reprint author), Massachusetts Gen Hosp, Dept Neurol, 15 Parkman St, Boston, MA 01945 USA. EM Pless.Misha@mgh.harvard.edu NR 12 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 EI 1536-7355 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD OCT PY 2013 VL 19 IS 7 BP 393 EP 396 DI 10.1097/RHU.0b013e3182a6ffc1 PG 4 WC Rheumatology SC Rheumatology GA 300KF UT WOS:000330462100008 PM 24048110 ER PT J AU Fostvedt, S Bruinsma, WE Neuhaus, V Stone, JH Mudgal, CS AF Fostvedt, Sigrid Bruinsma, Wendy E. Neuhaus, Valentin Stone, John H. Mudgal, Chaitanya S. TI Manifestations and Treatment of the Hand in Adult Congenital Erythropoietic Porphyria SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article DE congenital erythropoietic porphyria; finger; PIP arthrodesis; Gunther disease ID RADIOLOGICAL FEATURES; GUNTHERS-DISEASE; MANAGEMENT AB Congenital erythropoietic porphyria (CEP) is a rare enzymatic disorder of heme metabolism, leading to the accumulation of porphyrins in the skin and subdermal structures. We present the case of a 34-year-old, right-hand-dominant, male patient with CEP. The patient had developed a chronic open subluxation of the left index finger proximal interphalangeal joint due to skin necrosis. We successfully treated the patient with proximal interphalangeal arthrodesis. This case demonstrates that childhood-onset CEP can also manifest in the adult hand. Considering the patient's age, the destructive nature of the disease, and the poor quality of function in older patients with childhood CEP, surgical intervention was necessary to avoid further digital length loss. Although the treatment described in this case report is not uncommon, we found it essential to present this case because the clinical presentation of CEP is rare. C1 [Fostvedt, Sigrid; Bruinsma, Wendy E.; Neuhaus, Valentin; Mudgal, Chaitanya S.] Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. [Stone, John H.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Mudgal, CS (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM cmudgal@partners.org OI Neuhaus, Valentin/0000-0003-4012-5628 FU Gottfried und Julia Bangerter-Rhyner-Stiftung, Switzerland, for Scientific Research FX No relevant benefits in any form have been received or will be received related directly or indirectly to the subject of this article. V.N. is currently receiving a grant from the Gottfried und Julia Bangerter-Rhyner-Stiftung, Switzerland, for Scientific Research. NR 10 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 EI 1536-7355 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD OCT PY 2013 VL 19 IS 7 BP 402 EP 404 DI 10.1097/RHU.0b013e3182a70073 PG 3 WC Rheumatology SC Rheumatology GA 300KF UT WOS:000330462100011 PM 24048109 ER PT J AU Nichols, CR Roth, B Albers, P Einhorn, LH Foster, R Daneshmand, S Jewett, M Warde, P Sweeney, CJ Beard, C Powles, T Tyldesley, S So, A Porter, C Olgac, S Fizazi, K Hayes-Lattin, B Grimison, P Toner, G Cathomas, R Bokemeyer, C Kollmannsberger, C AF Nichols, Craig R. Roth, Bruce Albers, Peter Einhorn, Lawrence H. Foster, Richard Daneshmand, Siamak Jewett, Michael Warde, Padraig Sweeney, Christopher J. Beard, Clair Powles, Tom Tyldesley, Scott So, Alan Porter, Christopher Olgac, Semra Fizazi, Karim Hayes-Lattin, Brandon Grimison, Peter Toner, Guy Cathomas, Richard Bokemeyer, Carsten Kollmannsberger, Christian TI Active Surveillance Is the Preferred Approach to Clinical Stage I Testicular Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID GERM-CELL TUMORS; LYMPH-NODE DISSECTION; SEMINOMA; RISK; MANAGEMENT; SURVIVORS; TESTIS; TRIAL C1 [Nichols, Craig R.; Porter, Christopher; Olgac, Semra] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Roth, Bruce] Washington Univ, Sch Med, St Louis, MO USA. [Albers, Peter] Univ Dusseldorf, Univ Hosp Heinrich Heine, Dusseldorf, Germany. [Einhorn, Lawrence H.; Foster, Richard] Indiana Univ Sch Med, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46202 USA. [Daneshmand, Siamak] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Jewett, Michael; Warde, Padraig] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. [Sweeney, Christopher J.; Beard, Clair] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Powles, Tom] Queen Mary Univ London, St Bartholomews Hosp, Barts Canc Inst, London, England. [Tyldesley, Scott; So, Alan; Kollmannsberger, Christian] Univ British Columbia, Vancouver Canc Ctr, British Columbia Canc Agcy, Vancouver, BC V5Z 1M9, Canada. [Fizazi, Karim] Univ Paris 11, Inst Gustave Roussy, Paris, France. [Hayes-Lattin, Brandon] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Grimison, Peter] Univ Sydney, Sydney Canc Ctr, Royal Prince Alfred Hosp, Sydney, NSW 2006, Australia. [Toner, Guy] Univ Melbourne, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Cathomas, Richard] Kantonsspital Graubuenden, Chur, Switzerland. [Bokemeyer, Carsten] Univ Hamburg, Univ Med Ctr Eppendorf, Hamburg, Germany. RP Nichols, CR (reprint author), Virginia Mason Med Ctr, Seattle, WA 98101 USA. OI Daneshmand, Siamak/0000-0001-6224-9598; Toner, Guy/0000-0001-9873-3592 NR 27 TC 52 Z9 52 U1 1 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2013 VL 31 IS 28 BP 3490 EP 3493 DI 10.1200/JCO.2012.47.6010 PG 4 WC Oncology SC Oncology GA 301NM UT WOS:000330539000006 PM 24002502 ER PT J AU Cespedes, EM McDonald, J Haines, J Bottino, CJ Schmidt, ME Taveras, EM AF Cespedes, Elizabeth M. McDonald, Julia Haines, Jess Bottino, Clement J. Schmidt, Marie Evans Taveras, Elsie M. TI Obesity-related Behaviors of US- and Non-US-born Parents and Children in Low-income Households SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE childhood obesity; behavior; immigrant families; routines; home environment ID RANDOMIZED CONTROLLED-TRIAL; PRESCHOOL-AGED CHILDREN; BODY-MASS INDEX; SLEEP DURATION; WEIGHT STATUS; YOUNG-CHILDREN; UNITED-STATES; SCREENING QUESTIONNAIRE; IMMIGRANT CHILDREN; PHYSICAL-ACTIVITY AB Objective: To examine differences in obesity-related behaviors by parental US-born status among low-income, minority families participating in Healthy Habits, Happy Homes, an intervention trial to improve household routines for childhood obesity prevention. Evidence suggests lower obesity risk among adult immigrants, but research is inconclusive regarding the influence of having a non-US-born parent on childhood obesity. Method: We sampled 57 US-born and 64 non-US-born families of children aged 2 to 5.9 years living in the Boston area. At baseline, parents reported their own screen time, physical activity, diet, and sleep as well as their children's behaviors. We used linear and logistic regression to examine the association of parental US-born status with obesity-related behaviors. Results: Mean (SD) body mass index z score was 0.94 (1.16), and it did not differ between the groups. After adjusting for parental education and child race/ethnicity, children of non-US-born (vs US-born) parents had later bedtimes (0.81 hours later; 95% confidence interval [CI], 0.37-1.25) and wake-up times (0.56 hours later; 95% CI, 0.16-0.95) and engaged in less active play (0.15 fewer hr/d; 95% CI, -0.28 to -0.01). Non-US-born (vs US-born) parents had less screen exposure. Conclusion: In this cross-section of low-income, urban families, having a parent born outside the United States was associated with a profile of risk and protective behavior; adjustment for education and race/ethnicity removed the protective associations of parental nativity with child behavior. Obesity-related differences in behaviors and home environments should be considered when designing interventions targeting low-income communities with a high proportion of non-US-born participants. C1 [Cespedes, Elizabeth M.; McDonald, Julia; Taveras, Elsie M.] Harvard Univ, Sch Med, Dept Populat Med, Obes Prevent Program, Boston, MA USA. [Cespedes, Elizabeth M.; McDonald, Julia; Taveras, Elsie M.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Cespedes, Elizabeth M.; Taveras, Elsie M.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Cespedes, Elizabeth M.; Taveras, Elsie M.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Haines, Jess] Univ Guelph, Dept Family Relat & Appl Nutr, Guelph, ON N1G 2W1, Canada. [Bottino, Clement J.; Schmidt, Marie Evans] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Taveras, Elsie M.] MassGen Hosp Children, Div Gen Pediat, Boston, MA USA. RP Cespedes, EM (reprint author), Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM emc611@mail.harvard.edu OI Cespedes Feliciano, Elizabeth/0000-0003-1192-4017 FU Centers for Disease Control and Prevention's National Center for Chronic Disease Prevention and Health Promotion (Prevention Research Centers) [1U48DP00194] FX Supported by the Centers for Disease Control and Prevention's National Center for Chronic Disease Prevention and Health Promotion (Prevention Research Centers Grants, 1U48DP00194). NR 48 TC 2 Z9 2 U1 5 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X EI 1536-7312 J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD OCT PY 2013 VL 34 IS 8 BP 541 EP 548 PG 8 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 298XZ UT WOS:000330359300002 PM 24131876 ER PT J AU Nillni, YI Nosen, E Williams, PA Tracy, M Coffey, SF Galea, S AF Nillni, Yael I. Nosen, Elizabeth Williams, Patrick A. Tracy, Melissa Coffey, Scott F. Galea, Sandro TI Unique and Related Predictors of Major Depressive Disorder, Posttraumatic Stress Disorder, and Their Comorbidity After Hurricane Katrina SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Posttraumatic stress disorder; major depressive disorder; comorbidity; disasters ID MENTAL-HEALTH PROBLEMS; DISASTER VICTIMS; NATURAL DISASTER; PSYCHIATRIC-DISORDERS; PREVALENCE; PTSD; POPULATION; SYMPTOMS; ANDREW; PHQ-9 AB The current study examined demographic and psychosocial factors that predict major depressive disorder (MDD) and comorbid MDD/posttraumatic stress disorder (MDD/PTSD) diagnostic status after Hurricane Katrina, one of the deadliest and costliest hurricanes in the history of the United States. This study expanded on the findings published in the article by Galea, Tracy, Norris, and Coffey (J Trauma Stress 21: 357-368, 2008), which examined the same predictors for PTSD, to better understand related and unique predictors of MDD, PTSD, and MDD/PTSD comorbidity. A total of 810 individuals representative of adult residents living in the 23 southern-most counties of Mississippi before Hurricane Katrina were interviewed. Ongoing hurricane-related stressors, low social support, and hurricane-related financial loss were common predictors of MDD, PTSD, and MDD/PTSD, whereas educational and marital status emerged as unique predictors of MDD. Implications for postdisaster relief efforts that address the risk for both MDD and PTSD are discussed. C1 [Nillni, Yael I.; Nosen, Elizabeth; Williams, Patrick A.; Coffey, Scott F.] Univ Mississippi, Med Ctr, Jackson, MS USA. [Nillni, Yael I.] Univ Vermont, Burlington, VT 05405 USA. [Nosen, Elizabeth] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Tracy, Melissa; Galea, Sandro] Columbia Univ, New York, NY USA. RP Nillni, YI (reprint author), Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, 150 South Huntington Ave 116B-3, Boston, MA 02130 USA. EM yael.nillni2@va.gov RI Kilic, Cengiz/I-9145-2013 FU National Institutes of Health [MH 078152] FX This study was supported by grant MH 078152 from the National Institutes of Health. NR 35 TC 10 Z9 10 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD OCT PY 2013 VL 201 IS 10 BP 841 EP 847 DI 10.1097/NMD.0b013e3182a430a0 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 299DR UT WOS:000330375900002 PM 24080670 ER PT J AU Knouse, LE Traeger, L O'Cleirigh, C Safren, SA AF Knouse, Laura E. Traeger, Lara O'Cleirigh, Conall Safren, Steven A. TI Adult Attention Deficit Hyperactivity Disorder Symptoms and Five-Factor Model Traits in a Clinical Sample A Structural Equation Modeling Approach SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Attention deficit hyperactivity disorder; ADHD; personality; five-factor model; NEO-FFI; neuroticism; conscientiousness ID COVARIANCE STRUCTURE-ANALYSIS; DEFICIT/HYPERACTIVITY DISORDER; PERSONALITY-TRAITS; DISEASE PROGRESSION; EXECUTIVE FUNCTIONS; ADHD SYMPTOMS; PROFILES; THERAPY; HIV AB Relationships among attention deficit hyperactivity disorder (ADHD) symptoms and adult personality traits have not been examined in larger clinically diagnosed samples. We collected multisource ADHD symptom and self-report NEO Five-Factor Inventory (Costa and McCrae [Odessa, FL: Psychological Assessment Resources, Inc, 1992) data from 117 adults with ADHD and tested symptom-trait associations using structural equation modeling. The final model fit the data. Inattention was positively associated with neuroticism and negatively associated with conscientiousness. On the basis of ADHD expression in adulthood, hyperactivity and impulsivity were estimated as separate constructs and showed differential relationships to extraversion and agreeableness. A significant positive relationship between hyperactivity and conscientiousness arose in the context of other pathways. ADHD symptoms are reliably associated with personality traits, suggesting a complex interplay across development that warrants prospective study into adulthood. C1 [Safren, Steven A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Safren, SA (reprint author), Massachusetts Gen Hosp, One Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ssafren@partners.org FU NIH [5R01MH69812, 1R03MH60940] FX This research was supported by NIH Grants 5R01MH69812 and 1R03MH60940 to Steven A. Safren. NR 45 TC 4 Z9 4 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD OCT PY 2013 VL 201 IS 10 BP 848 EP 854 DI 10.1097/NMD.0b013e3182a5bf33 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 299DR UT WOS:000330375900003 PM 24080671 ER PT J AU Lewis-Fernandez, R Raggio, GA Gorritz, M Duan, N Marcus, S Cabassa, LJ Humensky, J Becker, AE Alarcon, RD Oquendo, MA Hansen, H Like, RC Weiss, M Desai, PN Jacobsen, FM Foulks, EF Primm, A Lu, F Kopelowicz, A Hinton, L Hinton, DE AF Lewis-Fernandez, Roberto Raggio, Greer A. Gorritz, Magdaliz Duan, Naihua Marcus, Sue Cabassa, Leopoldo J. Humensky, Jennifer Becker, Anne E. Alarcon, Renato D. Oquendo, Maria A. Hansen, Helena Like, Robert C. Weiss, Mitchell Desai, Prakash N. Jacobsen, Frederick M. Foulks, Edward F. Primm, Annelle Lu, Francis Kopelowicz, Alex Hinton, Ladson Hinton, Devon E. TI GAP-REACH A Checklist to Assess Comprehensive Reporting of Race, Ethnicity, and Culture in Psychiatric Publications SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Race; ethnicity; culture; checklist; psychiatric literature ID RANDOMIZED CONTROLLED-TRIALS; SOCIOECONOMIC-STATUS; CONSORT STATEMENT; CLINICAL-TRIALS; SOCIAL-CLASS; QUALITY; HEALTH; RACE/ETHNICITY; POPULATIONS; ARTICLES AB Growing awareness of health and health care disparities highlights the importance of including information about race, ethnicity, and culture (REC) in health research. Reporting of REC factors in research publications, however, is notoriously imprecise and unsystematic. This article describes the development of a checklist to assess the comprehensiveness and the applicability of REC factor reporting in psychiatric research publications. The 16-itemGAP-REACH (c) checklist was developed through a rigorous process of expert consensus, empirical content analysis in a sample of publications (N = 1205), and interrater reliability (IRR) assessment (N = 30). The items assess each section in the conventional structure of a health research article. Data from the assessment may be considered on an item-by-item basis or as a total score ranging from 0% to 100%. The final checklist has excellent IRR (kappa = 0.91). The GAP-REACH may be used by multiple research stakeholders to assess the scope of REC reporting in a research article. C1 [Lewis-Fernandez, Roberto; Duan, Naihua; Marcus, Sue; Cabassa, Leopoldo J.; Humensky, Jennifer; Oquendo, Maria A.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. [Lewis-Fernandez, Roberto; Gorritz, Magdaliz; Duan, Naihua; Marcus, Sue; Cabassa, Leopoldo J.; Humensky, Jennifer; Oquendo, Maria A.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Raggio, Greer A.] Drexel Univ, Dept Psychol, Philadelphia, PA 19104 USA. [Duan, Naihua; Marcus, Sue] Columbia Univ, Dept Biostat, Mailman Sch Publ Hlth, New York, NY 10027 USA. [Cabassa, Leopoldo J.] Columbia Univ, Sch Social Work, New York, NY 10027 USA. [Becker, Anne E.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Alarcon, Renato D.] Mayo Clin, Coll Med, Dept Psychiat & Psychol, Rochester, MN USA. [Hansen, Helena] NYU, Dept Psychiat, New York, NY 10016 USA. [Hansen, Helena] NYU, Dept Anthropol, New York, NY 10003 USA. [Like, Robert C.] UMDNJY Robert Wood Johnson Med Sch, Dept Family Med & Community Hlth, New Brunswick, NJ USA. [Weiss, Mitchell] Swiss Trop Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland. [Weiss, Mitchell] Univ Basel, CH-4003 Basel, Switzerland. [Desai, Prakash N.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Jacobsen, Frederick M.] George Washington Univ, Dept Psychiat & Behav Sci, Washington, DC USA. [Foulks, Edward F.] Tulane Univ, Dept Psychiat, New Orleans, LA 70118 USA. [Primm, Annelle] Amer Psychiat Assoc, Arlington, VA USA. Johns HopkinsMed Sch, Dept Psychiat, Baltimore, MD USA. [Lu, Francis; Hinton, Ladson] Univ Calif Davis, Dept Psychiat, Davis, CA 95616 USA. [Kopelowicz, Alex] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Hinton, Devon E.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Lewis-Fernandez, R (reprint author), New York State Psychiat Inst & Hosp, Unit 69,1051 Riverside Dr, New York, NY 10032 USA. EM rlewis@nyspi.columbia.edu OI kopelowicz, alex/0000-0002-1728-4105 FU National Institute of Mental Health [R21 MH066388, R34 MH073087, R01 MH077226]; Brain and Behavior Research Foundation; New York State Psychiatric Institute FX This study was supported by grants R21 MH066388, R34 MH073087, and R01 MH077226 from the National Institute of Mental Health and a grant award from the Brain and Behavior Research Foundation to Dr. Lewis-Fernandez and institutional funds from the New York State Psychiatric Institute. NR 49 TC 6 Z9 7 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD OCT PY 2013 VL 201 IS 10 BP 860 EP 871 DI 10.1097/NMD.0b013e3182a5c184 PG 12 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 299DR UT WOS:000330375900005 PM 24080673 ER PT J AU Jacobsen, HB Caban-Martinez, A Onyebeke, LC Sorensen, G Dennerlein, JT Reme, SE AF Jacobsen, Henrik Borsting Caban-Martinez, Alberto Onyebeke, Lynn C. Sorensen, Glorian Dennerlein, Jack T. Reme, Silje Endresen TI Construction Workers Struggle With a High Prevalence of Mental Distress, and This Is Associated With Their Pain and Injuries SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID LOW-BACK-PAIN; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; NATIONAL-COMORBIDITY-SURVEY; UNITED-STATES; OLDER CONSTRUCTION; RISK-FACTORS; PSYCHOLOGICAL DISTRESS; PSYCHIATRIC-DISORDERS; SCREENING SCALES; AGING WORKFORCE AB Objectives: We aimed to investigate how mental distress was associated with pain and injuries in a convenience sample of construction workers. Methods: A cross-sectional, mental health assessment was conducted in a convenience sample of construction workers (N = 172). A subsample participated in a clinical interview (n = 10). We used a cutoff (1.50 or greater) on Hopkins Symptom Checklist-25 to determine substantial mental distress and determined associations with pain and injury outcomes. Results: The prevalence of substantial mental distress was 16% in the workers. This was supported by follow-up clinical interviews where 9 of 10 workers fulfilled the criteria for a mental disorder. Substantial mental distress was associated with both injury rate and self-reported pain. Conclusion: This pilot study strongly suggests the need for rigorous studies on construction worker mental health and how it affects their work and well-being. C1 [Jacobsen, Henrik Borsting; Caban-Martinez, Alberto; Onyebeke, Lynn C.; Sorensen, Glorian; Dennerlein, Jack T.; Reme, Silje Endresen] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Dennerlein, Jack T.] Northeastern Univ, Boston, MA 02115 USA. [Sorensen, Glorian] Dana Farber Canc Inst, Boston, MA 02115 USA. [Reme, Silje Endresen] Uni Hlth, Uni Res, Bergen, Norway. [Jacobsen, Henrik Borsting] Norwegian Univ Sci & Technol, N-7034 Trondheim, Norway. RP Jacobsen, HB (reprint author), NTNU, Fac Med, Dept Publ Hlth, MTFS, POB 8905, N-7491 Trondheim, Norway. EM henrik.b.jacobsen@ntnu.no OI Dennerlein, Jack/0000-0001-7703-643X; Caban-Martinez, Alberto/0000-0002-5960-1308 FU National Institute for Occupational Safety and Health [U19 OH008861]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [T32 AR055885] FX This work was supported by a grant from the National Institute for Occupational Safety and Health (U19 OH008861) for the Harvard School of Public Health Center for Work, Health and Well-being, and a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant T32 AR055885) to the Clinical Orthopedic and Musculoskeletal Education and Training Program at Brigham and Women's Hospital, Harvard Medical School and Harvard School of Public Health, and the Liberty Mutual Harvard School of Public Health Program for Occupational Safety and Health. NR 42 TC 6 Z9 6 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD OCT PY 2013 VL 55 IS 10 BP 1197 EP 1204 DI 10.1097/JOM.0b013e31829c76b3 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 300FC UT WOS:000330448800011 PM 24064778 ER PT J AU Mejaddam, AY Birkhan, OA Sideris, AC Van der Wilden, GM Imam, AM Hwabejire, JO Chang, YC Velmahos, GC Fagenholz, PJ Yeh, DD de Moya, MA King, DR AF Mejaddam, Ali Y. Birkhan, Oscar A. Sideris, Antonis C. Van der Wilden, Gwendolyn M. Imam, Ayesha M. Hwabejire, John O. Chang, Yuchiao Velmahos, George C. Fagenholz, Peter J. Yeh, Daniel D. de Moya, Marc A. King, David Richard TI Real-time heart rate entropy predicts the need for lifesaving interventions in trauma activation patients SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Entropy; combat; triage; complexity; variability ID DIMINISHED PHYSIOLOGICAL RESERVE; RATE-VARIABILITY; PERIOD VARIABILITY; HEMORRHAGIC-SHOCK; RATE COMPLEXITY; MORTALITY; TRIAGE; INDICATOR AB BACKGROUND: Heart rate complexity (HRC), commonly described as a "new vital sign," has shown promise in predicting injury severity, but its use in clinical practice has been precluded by the absence of real-time data. This study was conducted to evaluate the utility of real-time, automated, instantaneous, hand-held heart rate entropy analysis in predicting the need for lifesaving interventions (LSIs). We hypothesized that real-time HRC would predict LSIs. METHODS: Prospective enrollment of patients who met criteria for trauma team activation was conducted at a Level I trauma center (September 2011 to February 2012). A novel, hand-held, portable device was used to measure HRC (by sample entropy) and time-domain heart rate variability continuously in real time for 2 hours after the moment of presentation. Electric impedance cardiography was used to determine cardiac output. Patients who received an LSI were compared with patients without any intervention (non-LSI). Multivariable analysis was performed to control for differences between the groups. RESULTS: Of 82 patients enrolled, 21 (26%) received 67 LSIs within 24 hours of hospital arrival. Initial systolic blood pressure was similar in both groups. LSI patients had a lower Glasgow Coma Scale (GCS) score (9.2 [5.1] vs. 14.9 [0.2], p < 0.0001). The mean (SD) HRC value on presentation was 0.8 (0.6) in the LSI group compared with 1.5 (0.6) in the non-LSI group (p G 0.0001). With the use of logistic regression, initial HRC was the only significant predictor of LSI. A cutoff value for HRC of 1.1 yields sensitivity, specificity, negative predictive value, and positive predictive value of 86%, 74%, 94%, and 53%, respectively, with an accuracy of 77% for predicting an LSI. CONCLUSION: Decreased HRC on hospital arrival is an independent predictor of the need for LSI in trauma activation patients. Real-time HRC may be a useful adjunct to standard vital signs monitoring and predicts LSIs. Copyright (C) 2013 by Lippincott Williams & Wilkins C1 [King, David Richard] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02141 USA. Harvard Univ, Sch Med, Boston, MA USA. RP King, DR (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02141 USA. EM Dking3@partners.org OI King, David/0000-0003-1028-1478 NR 29 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD OCT PY 2013 VL 75 IS 4 BP 607 EP 612 DI 10.1097/TA.0b013e31829bb991 PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 300IK UT WOS:000330457400010 PM 24064873 ER PT J AU Scott, NS AF Scott, Nandita S. TI Hypertensive pregnancy, menopausal symptoms, and heart disease: a motley crew of characters SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID CARDIOVASCULAR-DISEASE; PREECLAMPSIA; WOMEN; ASSOCIATION; RISK; DYSFUNCTION; HISTORY; UPDATE; AGE C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Scott, NS (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD OCT PY 2013 VL 20 IS 10 BP 993 EP 994 DI 10.1097/gme.0b013e3182a34c12 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 300LC UT WOS:000330464400002 PM 23982112 ER PT J AU Darney, BG Snowden, JM Cheng, YW Jacob, L Nicholson, JM Kaimal, A Dublin, S Getahun, D Caughey, AB AF Darney, Blair G. Snowden, Jonathan M. Cheng, Yvonne W. Jacob, Lorie Nicholson, James M. Kaimal, Anjali Dublin, Sascha Getahun, Darios Caughey, Aaron B. TI Elective Induction of Labor at Term Compared With Expectant Management Maternal and Neonatal Outcomes SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID CESAREAN DELIVERY; NULLIPAROUS WOMEN; GESTATIONAL-AGE; UNITED-STATES; RISK; COHORT; PROGRESSION; PREGNANCY AB OBJECTIVE: To test the association of elective induction of labor at term compared with expectant management and maternal and neonatal outcomes. METHODS: This was a retrospective cohort study of all deliveries without prior cesarean delivery in California in 2006 using linked hospital discharge and vital statistics data. We compared elective induction at each term gestational age (37-40 weeks) as defined by The Joint Commission with expectant management in vertex, non-anomalous, singleton deliveries. We used multivariable logistic regression to test the association of elective induction and cesarean delivery, operative vaginal delivery, maternal third- or fourth-degree lacerations, perinatal death, neonatal intensive care unit admission, respiratory distress, shoulder dystocia, hyperbilirubinemia, and macrosomia (birth weight greater than 4,000 g) at each gestational week, stratified by parity. RESULTS: The cesarean delivery rate was 16%, perinatal mortality was 0.2%, and neonatal intensive care unit admission was 6.2% (N=362,154). The odds of cesarean delivery were lower among women with elective induction compared with expectant management across all gestational ages and parity (37 weeks [odds ratio (OR) 0.44, 95% confidence interval (CI) 0.34-0.57], 38 weeks [OR 0.43, 95% CI 0.38-0.50], 39 weeks [OR 0.46, 95% CI 0.41-0.52], 40 weeks [OR 0.57, CI 0.50-0.65]). Elective induction was not associated with increased odds of severe lacerations, operative vaginal delivery, perinatal death, neonatal intensive care unit admission, respiratory distress, shoulder dystocia, or macrosomia at any term gestational age. Elective induction was associated with increased odds of hyperbilirubinemia at 37 and 38 weeks of gestation and shoulder dystocia at 39 weeks of gestation. CONCLUSION: Elective induction of labor is associated with decreased odds of cesarean delivery when compared with expectant management. C1 Oregon Hlth & Sci Univ, Portland, OR 97239 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Penn State Univ, Coll Med, Hershey, PA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Grp Hlth Res Inst, Seattle, WA USA. Kaiser Permanente So Calif, Pasadena, CA 91101 USA. RP Darney, BG (reprint author), Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Dept Med Informat & Clin Epidemiol, Mail Code L-466,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM darneyb@ohsu.edu FU Agency for Healthcare Research and Quality T32 postdoctoral award [HS017582]; National Institute on Aging [K23AG028954]; Health Resources and Services Administration/Maternal and Child Health [R40MC25694-01-00]; University of California, San Francisco Women's Reproductive Health Research Career Development Award, National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development [K12 HD001262] FX Dr. Darney was supported by an Agency for Healthcare Research and Quality T32 postdoctoral award (HS017582). Dr Dublin was supported by National Institute on Aging grant K23AG028954. Drs. Caughey and Snowden were supported by a Health Resources and Services Administration/Maternal and Child Health grant R40MC25694-01-00. Dr. Cheng is supported by the University of California, San Francisco Women's Reproductive Health Research Career Development Award, National Institutes of Health, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12 HD001262). NR 31 TC 44 Z9 44 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 2013 VL 122 IS 4 BP 761 EP 769 DI 10.1097/AOG.0b013e3182a6a4d0 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 300EJ UT WOS:000330446900006 PM 24084532 ER PT J AU Shanechi, MM Chemali, JJ Liberman, M Solt, K Brown, EN AF Shanechi, Maryam M. Chemali, Jessica J. Liberman, Max Solt, Ken Brown, Emery N. TI A Brain-Machine Interface for Control of Medically-Induced Coma SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID CLOSED-LOOP CONTROL; MODEL-PREDICTIVE CONTROL; DELIVERY-SYSTEM CLADS(TM); QUANTITATIVE EEG ANALYSIS; BISPECTRAL INDEX; BURST-SUPPRESSION; PERFORMANCE ASSESSMENT; PROPOFOL ANESTHESIA; FEEDBACK-CONTROL; GENERAL-ANESTHESIA AB Medically-induced coma is a drug-induced state of profound brain inactivation and unconsciousness used to treat refractory intracranial hypertension and to manage treatment-resistant epilepsy. The state of coma is achieved by continually monitoring the patient's brain activity with an electroencephalogram (EEG) and manually titrating the anesthetic infusion rate to maintain a specified level of burst suppression, an EEG marker of profound brain inactivation in which bursts of electrical activity alternate with periods of quiescence or suppression. The medical coma is often required for several days. A more rational approach would be to implement a brain-machine interface (BMI) that monitors the EEG and adjusts the anesthetic infusion rate in real time to maintain the specified target level of burst suppression. We used a stochastic control framework to develop a BMI to control medically-induced coma in a rodent model. The BMI controlled an EEG-guided closed-loop infusion of the anesthetic propofol to maintain precisely specified dynamic target levels of burst suppression. We used as the control signal the burst suppression probability (BSP), the brain's instantaneous probability of being in the suppressed state. We characterized the EEG response to propofol using a two-dimensional linear compartment model and estimated the model parameters specific to each animal prior to initiating control. We derived a recursive Bayesian binary filter algorithm to compute the BSP from the EEG and controllers using a linear-quadratic-regulator and a model-predictive control strategy. Both controllers used the estimated BSP as feedback. The BMI accurately controlled burst suppression in individual rodents across dynamic target trajectories, and enabled prompt transitions between target levels while avoiding both undershoot and overshoot. The median performance error for the BMI was 3.6%, the median bias was -1.4% and the overall posterior probability of reliable control was 1 (95% Bayesian credibility interval of [0.87, 1.0]). A BMI can maintain reliable and accurate real-time control of medically-induced coma in a rodent model suggesting this strategy could be applied in patient care. C1 [Shanechi, Maryam M.] Cornell Univ, Sch Elect & Comp Engn, Ithaca, NY 14850 USA. [Shanechi, Maryam M.] Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA. [Chemali, Jessica J.; Liberman, Max; Solt, Ken; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Brown, Emery N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Shanechi, MM (reprint author), Cornell Univ, Sch Elect & Comp Engn, Ithaca, NY 14850 USA. EM shanechi@cornell.edu; enb@neurostat.mit.edu OI Solt, Ken/0000-0001-5328-2062 FU National Institutes of Health, Bethesda, Maryland [DP1-OD003646, R01 GM104948, NIH K08-GM094394]; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts FX Support was provided by NIH Director's Pioneer Award DP1-OD003646 and NIH Director's Transformative Award R01 GM104948 (to ENB) and NIH K08-GM094394 (to KS) from the National Institutes of Health, Bethesda, Maryland, and by the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 63 TC 12 Z9 12 U1 3 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD OCT PY 2013 VL 9 IS 10 AR e1003284 DI 10.1371/journal.pcbi.1003284 PG 17 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 298WN UT WOS:000330355300041 PM 24204231 ER PT J AU Davis, LK Yu, DM Keenan, CL Gamazon, ER Konkashbaev, AI Derks, EM Neale, BM Yang, J Lee, SH Evans, P Barr, CL Bellodi, L Benarroch, F Berrio, GB Bienvenu, OJ Bloch, MH Blom, RM Bruun, RD Budman, CL Camarena, B Campbell, D Cappi, C Silgado, JCC Cath, DC Cavallini, MC Chavira, DA Chouinard, S Conti, DV Cook, EH Coric, V Cullen, BA Deforce, D Delorme, R Dion, Y Edlund, CK Egberts, K Falkai, P Fernandez, TV Gallagher, PJ Garrido, H Geller, D Girard, SL Grabe, HJ Grados, MA Greenberg, BD Gross-Tsur, V Haddad, S Heiman, GA Hemmings, SMJ Hounie, AG Illmann, C Jankovic, J Jenike, MA Kennedy, JL King, RA Kremeyer, B Kurlan, R Lanzagorta, N Leboyer, M Leckman, JF Lennertz, L Liu, C Lochner, C Lowe, TL Macciardi, F McCracken, JT McGrath, LM Restrepo, SCM Moessner, R Morgan, J Muller, H Murphy, DL Naarden, AL Ochoa, WC Ophoff, RA Osiecki, L Pakstis, AJ Pato, MT Pato, CN Piacentini, J Pittenger, C Pollak, Y Rauch, SL Renner, TJ Reus, VI Richter, MA Riddle, MA Robertson, MM Romero, R Rosario, MC Rosenberg, D Rouleau, GA Ruhrmann, S Ruiz-Linares, A Sampaio, AS Samuels, J Sandor, P Sheppard, B Singer, HS Smit, JH Stein, DJ Strengman, E Tischfield, JA Duarte, AVV Vallada, H Van Nieuwerburgh, F Veenstra-VanderWeele, J Walitza, S Wang, Y Wendland, JR Westenberg, HGM Shugart, YY Miguel, EC McMahon, W Wagner, M Nicolini, H Posthuma, D Hanna, GL Heutink, P Denys, D Arnold, PD Oostra, BA Nestadt, G Freimer, NB Pauls, DL Wray, NR Stewart, SE Mathews, CA Knowles, JA Cox, NJ Scharf, JM AF Davis, Lea K. Yu, Dongmei Keenan, Clare L. Gamazon, Eric R. Konkashbaev, Anuar I. Derks, Eske M. Neale, Benjamin M. Yang, Jian Lee, S. Hong Evans, Patrick Barr, Cathy L. Bellodi, Laura Benarroch, Fortu Berrio, Gabriel Bedoya Bienvenu, Oscar J. Bloch, Michael H. Blom, Rianne M. Bruun, Ruth D. Budman, Cathy L. Camarena, Beatriz Campbell, Desmond Cappi, Carolina Silgado, Julio C. Cardona Cath, Danielle C. Cavallini, Maria C. Chavira, Denise A. Chouinard, Sylvain Conti, David V. Cook, Edwin H. Coric, Vladimir Cullen, Bernadette A. Deforce, Dieter Delorme, Richard Dion, Yves Edlund, Christopher K. Egberts, Karin Falkai, Peter Fernandez, Thomas V. Gallagher, Patience J. Garrido, Helena Geller, Daniel Girard, Simon L. Grabe, Hans J. Grados, Marco A. Greenberg, Benjamin D. Gross-Tsur, Varda Haddad, Stephen Heiman, Gary A. Hemmings, Sian M. J. Hounie, Ana G. Illmann, Cornelia Jankovic, Joseph Jenike, Michael A. Kennedy, James L. King, Robert A. Kremeyer, Barbara Kurlan, Roger Lanzagorta, Nuria Leboyer, Marion Leckman, James F. Lennertz, Leonhard Liu, Chunyu Lochner, Christine Lowe, Thomas L. Macciardi, Fabio McCracken, James T. McGrath, Lauren M. Restrepo, Sandra C. Mesa Moessner, Rainald Morgan, Jubel Muller, Heike Murphy, Dennis L. Naarden, Allan L. Ochoa, William Cornejo Ophoff, Roel A. Osiecki, Lisa Pakstis, Andrew J. Pato, Michele T. Pato, Carlos N. Piacentini, John Pittenger, Christopher Pollak, Yehuda Rauch, Scott L. Renner, Tobias J. Reus, Victor I. Richter, Margaret A. Riddle, Mark A. Robertson, Mary M. Romero, Roxana Rosario, Maria C. Rosenberg, David Rouleau, Guy A. Ruhrmann, Stephan Ruiz-Linares, Andres Sampaio, Aline S. Samuels, Jack Sandor, Paul Sheppard, Brooke Singer, Harvey S. Smit, Jan H. Stein, Dan J. Strengman, E. Tischfield, Jay A. Duarte, Ana V. Valencia Vallada, Homero Van Nieuwerburgh, Filip Veenstra-VanderWeele, Jeremy Walitza, Susanne Wang, Ying Wendland, Jens R. Westenberg, Herman G. M. Shugart, Yin Yao Miguel, Euripedes C. McMahon, William Wagner, Michael Nicolini, Humberto Posthuma, Danielle Hanna, Gregory L. Heutink, Peter Denys, Damiaan Arnold, Paul D. Oostra, Ben A. Nestadt, Gerald Freimer, Nelson B. Pauls, David L. Wray, Naomi R. Stewart, S. Evelyn Mathews, Carol A. Knowles, James A. Cox, Nancy J. Scharf, Jeremiah M. TI Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture SO PLOS GENETICS LA English DT Article ID MISSING HERITABILITY; TIC DISORDERS; NEUROPSYCHIATRIC DISORDERS; COMPLEX DISEASES; COMMON SNPS; GILLES; FAMILY; BRAIN; EXPRESSION; AUTISM AB The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures. C1 [Davis, Lea K.; Gamazon, Eric R.; Konkashbaev, Anuar I.; Evans, Patrick; Cox, Nancy J.] Univ Chicago, Dept Med, Med Genet Sect, Chicago, IL 60637 USA. [Yu, Dongmei; Haddad, Stephen; Illmann, Cornelia; McGrath, Lauren M.; Osiecki, Lisa; Pauls, David L.; Scharf, Jeremiah M.] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat,Sch Med, Psychiat & Neurodev Genet Unit,Ctr Human Genet Re, Boston, MA USA. [Yu, Dongmei; Neale, Benjamin M.; Scharf, Jeremiah M.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Keenan, Clare L.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Keenan, Clare L.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Derks, Eske M.; Blom, Rianne M.; Denys, Damiaan] Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands. [Neale, Benjamin M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Yang, Jian] Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia. [Yang, Jian; Lee, S. Hong; Wray, Naomi R.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia. [Barr, Cathy L.] Univ Hlth Network, Toronto Western Res Inst, Toronto, ON, Canada. [Barr, Cathy L.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Bellodi, Laura] Univ Vita Salute San Raffaele, Milan, Italy. [Benarroch, Fortu] Hadassah Hebrew Univ Med Ctr, Herman Dana Div Child & Adolescent Psychiat, Jerusalem, Israel. [Berrio, Gabriel Bedoya; Silgado, Julio C. Cardona; Restrepo, Sandra C. Mesa; Ochoa, William Cornejo; Duarte, Ana V. Valencia] Univ Pontificia Bolivariana, Univ Antioquia, Medellin, Colombia. [Bienvenu, Oscar J.; Cullen, Bernadette A.; Gallagher, Patience J.; Grados, Marco A.; Riddle, Mark A.; Samuels, Jack; Wang, Ying; Nestadt, Gerald] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Bloch, Michael H.; Coric, Vladimir] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Bloch, Michael H.; Fernandez, Thomas V.] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. [Bruun, Ruth D.] North Shore Long Isl Jewish Med Ctr, Manhasset, NY USA. [Bruun, Ruth D.] NYU Med Ctr, New York, NY 10016 USA. [Budman, Cathy L.] North Shore Long Isl Jewish Hlth Syst, Manhasset, NY USA. [Budman, Cathy L.] Hofstra Univ, Sch Med, Hempstead, NY 11550 USA. [Camarena, Beatriz] Inst Nacl Psiquiatria Ramon de la Fuente Muniz, Mexico City, DF, Mexico. [Campbell, Desmond; Kremeyer, Barbara; Muller, Heike; Robertson, Mary M.; Ruiz-Linares, Andres] UCL, London, England. [Campbell, Desmond] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China. [Cappi, Carolina; Vallada, Homero; Miguel, Euripedes C.] Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. [Cath, Danielle C.; Smit, Jan H.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands. [Cath, Danielle C.] Univ Utrecht, Dept Clin & Hlth Psychol, Utrecht, Netherlands. [Cath, Danielle C.] Altrecht Acad Anxiety Ctr, Utrecht, Netherlands. [Cavallini, Maria C.] Univ Milan, Osped San Raffaele, I-20127 Milan, Italy. [Chavira, Denise A.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Chavira, Denise A.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Chouinard, Sylvain; Girard, Simon L.] Univ Montreal, Montreal, PQ, Canada. [Conti, David V.; Edlund, Christopher K.] Univ Calif Los Angeles, Keck Sch Med, Div Biostat, Dept Preventat Med, Los Angeles, CA USA. [Cook, Edwin H.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60612 USA. [Deforce, Dieter; Van Nieuwerburgh, Filip] Univ Ghent, Lab Pharmaceut Biotechnol, B-9000 Ghent, Belgium. [Delorme, Richard] Inst Pasteur, Paris, France. [Delorme, Richard; Leboyer, Marion] French Natl Sci Fdn, Fondat Fondamental, Creteil, France. [Delorme, Richard; Leboyer, Marion] Hop Robert Debre, AP HP, Dept Child & Adolescent Psychiat, F-75019 Paris, France. [Dion, Yves] Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada. [Egberts, Karin; Renner, Tobias J.] Univ Wurzburg, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-97070 Wurzburg, Germany. [Falkai, Peter] Univ Munich, Dept Psychiat & Psychotherapy, Munich, Germany. [Fernandez, Thomas V.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp,OCD Program, Boston, MA 02115 USA. [Grabe, Hans J.] Univ Med Greifswald, Helios Hosp Stralsund, Dept Psychiat & Psychotherapy, Greifswald, Germany. [Garrido, Helena; Greenberg, Benjamin D.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [Geller, Daniel; Gross-Tsur, Varda; Pollak, Yehuda] Shaare Zedek Med Ctr, Neuropediatr Unit, Jerusalem, Israel. [Heiman, Gary A.; Tischfield, Jay A.] Rutgers State Univ, Dept Genet, Human Genet Inst New Jersey, Piscataway, NJ USA. [Hemmings, Sian M. J.] Univ Stellenbosch, Dept Psychiat, ZA-7600 Stellenbosch, South Africa. [Hounie, Ana G.; Sampaio, Aline S.] Univ Sao Paulo, Fac Med, Dept Psychiat, BR-05508 Sao Paulo, Brazil. [Jankovic, Joseph] Baylor Coll Med, Dept Neurol, Parkinsons Dis Ctr, Houston, TX 77030 USA. [Jankovic, Joseph] Baylor Coll Med, Dept Neurol, Movement Disorders Clin, Houston, TX 77030 USA. [Jenike, Michael A.; Stewart, S. Evelyn] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Kennedy, James L.] Ctr Addict & Mental Hlth, Neurogenet Sect, Toronto, ON, Canada. [Kennedy, James L.; Richter, Margaret A.; Arnold, Paul D.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [King, Robert A.] Yale Univ, Sch Med, Dept Genet, Yale Child Study Ctr, New Haven, CT 06510 USA. [Kurlan, Roger] Overlook Hosp, Atlantic Neurosci Inst, Summit, NJ USA. [Lanzagorta, Nuria] Carracci Med Grp, Mexico City, DF, Mexico. [Leboyer, Marion] Inst Mondor Rech Biomed, Creteil, France. [Leckman, James F.] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. [Lennertz, Leonhard; Moessner, Rainald; Wagner, Michael] Univ Bonn, Dept Psychiat & Psychotherapy, Bonn, Germany. [Liu, Chunyu] Univ Illinois, Dept Psychiat, Inst Human Genet, Chicago, IL 60612 USA. [Lochner, Christine] Univ Stellenbosch, Dept Psychiat, MRC Unit Anxiety & Stress Disorders, ZA-7600 Stellenbosch, South Africa. [Lowe, Thomas L.; Reus, Victor I.; Sheppard, Brooke; Mathews, Carol A.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Macciardi, Fabio; McCracken, James T.] UCI, Sch Med, Dept Psychiat & Human Behav, Irvine, CA USA. [Morgan, Jubel] Univ Utah, Salt Lake City, UT USA. [Murphy, Dennis L.; Wendland, Jens R.] NIMH Intramural Res Program, Clin Sci Lab, Bethesda, MD USA. [Naarden, Allan L.] Med City Dallas Hosp, Dept Clin Res, Dallas, TX USA. [Ophoff, Roel A.] Univ Med Ctr, Rudolf Magnus Inst Neurosci, Dept Psychiat, Utrecht, Netherlands. [Ophoff, Roel A.; Freimer, Nelson B.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Ctr Neurobehav Genet, Los Angeles, CA 90024 USA. [Pakstis, Andrew J.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Pato, Michele T.; Pato, Carlos N.; Knowles, James A.] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. [Piacentini, John] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Pittenger, Christopher] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Pittenger, Christopher] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Pittenger, Christopher] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. [Rauch, Scott L.] Partners Psychiat & McLean Hosp, Boston, MA USA. [Richter, Margaret A.] Sunnybrook Hlth Sci Ctr, Frederick W Thompson Anxiety Disorders Ctr, Toronto, ON M4N 3M5, Canada. [Robertson, Mary M.] St George Hosp, London, England. [Robertson, Mary M.] Sch Med, London, England. [Romero, Roxana] Hosp Nacl Ninos Dr Carlos Saenz Herrera, San Jose, Costa Rica. [Rosario, Maria C.] Univ Fed Sao Paulo, Dept Psychiat, Child & Adolescent Psychiat Unit UPIA, Sao Paulo, Brazil. [Rosenberg, David] Wayne State Univ, Dept Psychiat & Behav Neurosci, Detroit, MI 48207 USA. [Rosenberg, David] Detroit Med Ctr, Detroit, MI USA. [Rouleau, Guy A.] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. [Ruhrmann, Stephan] Univ Cologne, Dept Psychiat & Psychotherapy, D-50931 Cologne, Germany. [Sampaio, Aline S.] Univ Fed Bahia, Univ Hlth Care Serv SMURB, Salvador, BA, Brazil. [Sandor, Paul] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Sandor, Paul] Univ Hlth Network, Toronto Western Res Inst, Toronto, ON, Canada. [Sandor, Paul] Youthdale Treatment Ctr, Toronto, ON, Canada. [Singer, Harvey S.] Johns Hopkins Univ Sch Med, Baltimore, MD USA. [Stein, Dan J.] Univ Cape Town, ZA-7925 Cape Town, South Africa. [Strengman, E.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Veenstra-VanderWeele, Jeremy] Vanderbilt Univ, Kennedy Ctr Res Human Dev, Dept Psychiat, Nashville, TN 37235 USA. [Veenstra-VanderWeele, Jeremy] Vanderbilt Univ, Kennedy Ctr Res Human Dev, Dept Pediat & Pharmacol, Nashville, TN 37235 USA. [Veenstra-VanderWeele, Jeremy] Vanderbilt Univ, Inst Brain, Nashville, TN 37235 USA. [Walitza, Susanne] Univ Zurich, Dept Child & Adolescent Psychiat, Zurich, Switzerland. [Walitza, Susanne] Univ Wurzburg, Dept Child & Adolescent Psychiat, D-97070 Wurzburg, Germany. [Westenberg, Herman G. M.] Univ Amsterdam, Acad Med Ctr, Ctr Psychiat, NL-1105 BC Amsterdam, Netherlands. [Westenberg, Herman G. M.; Denys, Damiaan] Inst Royal Netherlands Acad Arts & Sci NIN KNAW, Netherlands Inst Neurosci, Amsterdam, Netherlands. [Shugart, Yin Yao] NIMH Intramural Res Program, Unit Stat Genom, Bethesda, MD USA. [McMahon, William] Univ Utah, Dept Psychiat, Salt Lake City, UT USA. [Nicolini, Humberto] Natl Inst Genom Med SAP, Carracci Med Grp, Mexico City, DF, Mexico. [Posthuma, Danielle] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Funct Genom, Amsterdam, Netherlands. [Posthuma, Danielle] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. [Posthuma, Danielle] Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands. [Hanna, Gregory L.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Heutink, Peter] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Sect Med Genom, Amsterdam, Netherlands. [Heutink, Peter] German Ctr Neurodegenerat Dis, Tubingen, Germany. [Arnold, Paul D.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada. [Oostra, Ben A.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. [Stewart, S. Evelyn] Univ British Columbia, British Columbia Mental Hlth & Addict Res Inst, Vancouver, BC V5Z 1M9, Canada. [Scharf, Jeremiah M.] Brigham & Womens Hosp, Div Cognit & Behav Neurol, Boston, MA 02115 USA. [Scharf, Jeremiah M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Davis, LK (reprint author), Univ Chicago, Dept Med, Med Genet Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM lea.k.davis@gmail.com; jscharf@partners.org RI Renner, Tobias/I-2120-2013; Lee, Sang Hong/A-2569-2011; Wray, Naomi/C-8639-2015; Macciardi, Fabio/N-3768-2014; Wagner, Michael/E-2325-2011; Van Nieuwerburgh, Filip/H-9697-2015; reus, victor/I-7923-2015; Yang, Jian/A-5852-2010; Stein, Dan/A-1752-2008; Derks, Eske/A-1652-2017; Veenstra-VanderWeele, Jeremy/K-1935-2015; Vallada, Homero/D-1333-2014 OI Hemmings, Sian/0000-0001-8461-1017; Gamazon, Eric/0000-0003-4204-8734; Lanzagorta, Nuria/0000-0001-6769-6813; Campbell, Desmond/0000-0003-1085-714X; Nicolini, Humberto/0000-0003-2494-0067; Hanna, Gregory/0000-0002-0742-6990; Samuels, Jack/0000-0002-6715-7905; Walitza, Susanne/0000-0002-8161-8683; Barr, Cathy/0000-0003-0361-0106; Fernandez, Thomas V/0000-0003-0830-022X; Tischfield, Jay/0000-0003-3217-8287; Lee, Sang Hong/0000-0001-9701-2718; Wray, Naomi/0000-0001-7421-3357; Macciardi, Fabio/0000-0003-0537-4266; Wagner, Michael/0000-0003-2589-6440; Van Nieuwerburgh, Filip/0000-0001-8815-5485; reus, victor/0000-0002-8193-5697; Yang, Jian/0000-0003-2001-2474; Stein, Dan/0000-0001-7218-7810; Derks, Eske/0000-0002-6292-6883; Veenstra-VanderWeele, Jeremy/0000-0002-6349-1076; Vallada, Homero/0000-0001-5123-8295 FU Judah Foundation; NIH [NS40024, NS16648, MH079489, MH073250, NS037484, 1R01MH079487-01A1, K20 MH01065, R01 MH58376, MH085057, MH079494, HHSN268200782096C]; Tourette Syndrome Association International Consortium for Genetics (TSAICG); New Jersey Center for Tourette Syndrome and Associated Disorders; NIMH [R01MH092293]; Obsessive Compulsive Foundation; Ontario Mental Health Foundation; Tourette Syndrome Association; American Academy of Child and Adolescent Psychiatry (AACAP); Anxiety Disorders Association of America (ADAA); University of British Columbia; Michael Smith Foundation; American Recovery and Re-investment Act (ARRA) [NS40024-07S1, NS16648-29S1]; Australian Research Council [FT0991360, DE130100614]; Australian National Health and Medical Research Council [1047956, 1052684]; German Research Foundation [DFG GR 1912/1-1]; NIH Genes, Environment and Health Initiative [GEI] [U01 HG004422]; Gene Environment Association Studies (GENEVA) under GEI; NIH GEI [U01HG004438]; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; [R01 MH090937]; [P50MH094267] FX This work was supported by a grant from the Judah Foundation, NIH grant NS40024 to DLP/JMS and the Tourette Syndrome Association International Consortium for Genetics (TSAICG), NIH grant NS16648, MH079489, and MH073250 to DLP, NIH grant NS037484 to NBF, NIH grant 1R01MH079487-01A1 to JTM, New Jersey Center for Tourette Syndrome and Associated Disorders and NIMH (R01MH092293) to GAH/RAK/JAT, NIH grant K20 MH01065 and R01 MH58376 and a grant from the Obsessive Compulsive Foundation to GLH, Ontario Mental Health Foundation grant to PR and JLK, and a grant from the Tourette Syndrome Association and NIH grant MH085057 to JMS, MH079494 to JAK and the OCD Collaborative Genetics Association Study which supported the imputation, by an American Academy of Child and Adolescent Psychiatry (AACAP) Early Investigator Research Grant, an Anxiety Disorders Association of America (ADAA) Junior Investigator Research Grant, the University of British Columbia and a Michael Smith Foundation Clinical Research Scholar Award to SES, and American Recovery and Re-investment Act (ARRA) awards NS40024-07S1 to DLP/JMS and NS16648-29S1 to DLP. Additional support for analysis was provided by R01 MH090937 and P50MH094267 awarded to NJC. Support was also provided by the Australian Research Council FT0991360 (NRW), DE130100614 (SHL) and the Australian National Health and Medical Research Council: 1047956 (NRW), 1052684 (JY), and the German Research Foundation (DFG GR 1912/1-1) to HJG and to PF, SR, MW. Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative [GEI] (U01 HG004422). SAGE is one of the genome-wide association studies funded as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of datasets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (COGA; U10 AA008401), the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01 CA089392), and the Family Study of Cocaine Dependence (FSCD; R01 DA013423), and R01-MH-50214 (GN). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01HG004438), the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the NIH contract "High throughput genotyping for studying the genetic contributions to human disease" (HHSN268200782096C). The datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/projects/gap/cgibin/study.cgi?study_id=phs00 0092.v1.p1 through dbGaP accession number phs000092.v1.p. None of the funding agencies for this project (NINDS, NIMH, the Tourette Syndrome Association and the Judah Foundation) had any influence or played any role in a) the design or conduct of the study; b) management, analysis or interpretation of the data; c) preparation, review or approval of the manuscript. NR 61 TC 74 Z9 74 U1 5 U2 37 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2013 VL 9 IS 10 AR e1003864 DI 10.1371/journal.pgen.1003864 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 299AR UT WOS:000330367200041 PM 24204291 ER PT J AU Pinto, RM Dragileva, E Kirby, A Lloret, A Lopez, E St Claire, J Panigrahi, GB Hou, CX Holloway, K Gillis, T Guide, JR Cohen, PE Li, GM Pearson, CE Daly, MJ Wheeler, VC AF Pinto, Ricardo Mouro Dragileva, Ella Kirby, Andrew Lloret, Alejandro Lopez, Edith St Claire, Jason Panigrahi, Gagan B. Hou, Caixia Holloway, Kim Gillis, Tammy Guide, Jolene R. Cohen, Paula E. Li, Guo-Min Pearson, Christopher E. Daly, Mark J. Wheeler, Vanessa C. TI Mismatch Repair Genes Mlh1 and Mlh3 Modify CAG Instability in Huntington's Disease Mice: Genome-Wide and Candidate Approaches SO PLOS GENETICS LA English DT Article ID TRINUCLEOTIDE REPEAT INSTABILITY; KNOCK-IN MICE; AGE-OF-ONSET; DNA-REPAIR; SACCHAROMYCES-CEREVISIAE; SOMATIC EXPANSION; MOUSE MODEL; QUANTITATIVE TRAITS; FUNCTIONAL-ANALYSIS; PROTEIN EXPRESSION AB The Huntington's disease gene (HTT) CAG repeat mutation undergoes somatic expansion that correlates with pathogenesis. Modifiers of somatic expansion may therefore provide routes for therapies targeting the underlying mutation, an approach that is likely applicable to other trinucleotide repeat diseases. Huntington's disease Hdh(Q111) mice exhibit higher levels of somatic HTT CAG expansion on a C57BL/6 genetic background (B6.Hdh(Q111)) than on a 129 background (129.Hdh(Q111)). Linkage mapping in (B6x129).Hdh(Q111) F2 intercross animals identified a single quantitative trait locus underlying the strain-specific difference in expansion in the striatum, implicating mismatch repair (MMR) gene Mlh1 as the most likely candidate modifier. Crossing B6.Hdh(Q111) mice onto an Mlh1 null background demonstrated that Mlh1 is essential for somatic CAG expansions and that it is an enhancer of nuclear huntingtin accumulation in striatal neurons. Hdh(Q111) somatic expansion was also abolished in mice deficient in the Mlh3 gene, implicating MutL gamma (MLH1-MLH3) complex as a key driver of somatic expansion. Strikingly, Mlh1 and Mlh3 genes encoding MMR effector proteins were as critical to somatic expansion as Msh2 and Msh3 genes encoding DNA mismatch recognition complex MutS beta (MSH2-MSH3). The Mlh1 locus is highly polymorphic between B6 and 129 strains. While we were unable to detect any difference in base-base mismatch or short slipped-repeat repair activity between B6 and 129 MLH1 variants, repair efficiency was MLH1 dose-dependent. MLH1 mRNA and protein levels were significantly decreased in 129 mice compared to B6 mice, consistent with a dose-sensitive MLH1-dependent DNA repair mechanism underlying the somatic expansion difference between these strains. Together, these data identify Mlh1 and Mlh3 as novel critical genetic modifiers of HTT CAG instability, point to Mlh1 genetic variation as the likely source of the instability difference in B6 and 129 strains and suggest that MLH1 protein levels play an important role in driving of the efficiency of somatic expansions. C1 [Pinto, Ricardo Mouro; Dragileva, Ella; Lloret, Alejandro; Lopez, Edith; St Claire, Jason; Gillis, Tammy; Guide, Jolene R.; Wheeler, Vanessa C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kirby, Andrew; Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Kirby, Andrew; Daly, Mark J.] MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. [Kirby, Andrew; Daly, Mark J.] Harvard, Cambridge, MA USA. [Panigrahi, Gagan B.; Pearson, Christopher E.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada. [Panigrahi, Gagan B.; Pearson, Christopher E.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Hou, Caixia; Li, Guo-Min] Univ Kentucky, Grad Ctr Toxicol, Coll Med, Lexington, KY 40536 USA. [Hou, Caixia; Li, Guo-Min] Univ Kentucky, Coll Med, Markey Canc Ctr, Lexington, KY 40536 USA. [Holloway, Kim; Cohen, Paula E.] Cornell Univ, Dept Biomed Sci, Ithaca, NY USA. RP Pinto, RM (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM wheeler@chgr.mgh.harvard.edu RI Li, Guo-Min/I-5016-2014; OI Li, Guo-Min/0000-0002-9842-4578 FU National Institutes of Health [NS049206, GM089684]; Huntington's Society of Canada; Hereditary disease foundation FX This work was supported by the National Institutes of Health [NS049206 to VCW; GM089684 to GML], the Huntington's Society of Canada (www.huntingtonsociety.ca) [VCW] and a Hereditary disease foundation (www.hdfoundation.org) postdoctoral fellowship [KH]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 97 TC 31 Z9 31 U1 0 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2013 VL 9 IS 10 AR e1003930 DI 10.1371/journal.pgen.1003930 PG 19 WC Genetics & Heredity SC Genetics & Heredity GA 299AR UT WOS:000330367200083 PM 24204323 ER PT J AU Sakurai, D Zhao, J Deng, Y Kelly, JA Brown, EE Harley, JB Bae, SC Alarcon-Riqueime, ME Edberg, JC Kimberly, RP Ramsey-Goldman, R Petri, MA Reveille, JD Vila, LM Alarcon, GS Kaufman, KM Vyse, TJ Jacob, CO Gaffney, PM Sivils, KM James, JA Kamen, DL Gilkeson, GS Niewold, TB Merrill, JT Scofield, RH Criswell, LA Stevens, AM Boackle, SA Kim, JH Choi, J Pons-Estel, BA Freedman, BI Anaya, JM Martin, J Yu, CY Chang, DM Song, YW Langefeld, CD Chen, WL Grossman, JM Cantor, RM Hahn, BH Tsao, BP AF Sakurai, Daisuke Zhao, Jian Deng, Yun Kelly, Jennifer A. Brown, Elizabeth E. Harley, John B. Bae, Sang-Cheol Alarcon-Riqueime, Marta E. Edberg, Jeffrey C. Kimberly, Robert P. Ramsey-Goldman, Rosalind Petri, Michelle A. Reveille, John D. Vila, Luis M. Alarcon, Graciela S. Kaufman, Kenneth M. Vyse, Timothy J. Jacob, Chaim O. Gaffney, Patrick M. Sivils, Kathy Moser James, Judith A. Kamen, Diane L. Gilkeson, Gary S. Niewold, Timothy B. Merrill, Joan T. Scofield, R. Hal Criswell, Lindsey A. Stevens, Anne M. Boackle, Susan A. Kim, Jae-Hoon Choi, Jiyoung Pons-Estel, Bernardo A. Freedman, Barry I. Anaya, Juan-Manuel Martin, Javier Yu, C. Yung Chang, Deh-Ming Song, Yeong Wook Langefeld, Carl D. Chen, Weiling Grossman, Jennifer M. Cantor, Rita M. Hahn, Bevra H. Tsao, Betty P. CA BIOLUPUS & GENLES networks Argentine Collaborative Grp TI Preferential Binding to Elk-1 by SLE-Associated IL10 Risk Allele Upregulates IL10 Expression SO PLOS GENETICS LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENOME-WIDE ASSOCIATION; INFLAMMATORY-BOWEL-DISEASE; HUMAN B-LYMPHOCYTES; CELL-DERIVED IL-10; RHEUMATOID-ARTHRITIS; SUSCEPTIBILITY LOCI; AUTOIMMUNE-DISEASE; INTERLEUKIN-10 PRODUCTION; 1ST-DEGREE RELATIVES AB Immunoregulatory cytokine interleukin-10 (IL-10) is elevated in sera from patients with systemic lupus erythematosus (SLE) correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s) and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA) (P = 2.7x10(-8), OR = 1.30), but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively), and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G) allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1) detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele upregulates IL10 expression and confers increased risk for SLE in European Americans. C1 [Sakurai, Daisuke; Zhao, Jian; Deng, Yun; Chen, Weiling; Grossman, Jennifer M.; Hahn, Bevra H.; Tsao, Betty P.] Univ Calif Los Angeles, David Geffen Sch Med, Div Rheumatol, Los Angeles, CA 90095 USA. [Kelly, Jennifer A.; Alarcon-Riqueime, Marta E.; Gaffney, Patrick M.; Sivils, Kathy Moser; James, Judith A.; Scofield, R. Hal] Oklahoma Med Res Fdn, Arthritis & Clin Immunol Program, Oklahoma City, OK 73104 USA. [Brown, Elizabeth E.; Edberg, Jeffrey C.; Kimberly, Robert P.; Alarcon, Graciela S.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Brown, Elizabeth E.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Harley, John B.; Kaufman, Kenneth M.] Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA. [Harley, John B.; Kaufman, Kenneth M.] Cincinnati Childrens Hosp Med Ctr, Ctr Autoimmune Genom & Etiol, Cincinnati, OH 45229 USA. [Harley, John B.; Kaufman, Kenneth M.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Bae, Sang-Cheol; Kim, Jae-Hoon; Choi, Jiyoung] Hanyang Univ, Hosp Rheumat Dis, Dept Rheumatol, Seoul 133791, South Korea. [Alarcon-Riqueime, Marta E.] Univ Granada Junta Andalucia, Pfizer, GENYO, Ctr Genom & Invest Oncol, Granada, Spain. [Ramsey-Goldman, Rosalind] Northwestern Univ, Feinberg Sch Med, Div Rheumatol, Chicago, IL 60611 USA. [Petri, Michelle A.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Reveille, John D.] Univ Texas Houston, Hlth Sci Ctr, Dept Internal Med, Houston, TX 77225 USA. [Vila, Luis M.] Univ Puerto Rico, Dept Med, San Juan, PR 00936 USA. [Vyse, Timothy J.] Kings Coll London, Div Genet, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Div Mol Med, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Div Immunol, London WC2R 2LS, England. [Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [James, Judith A.; Scofield, R. Hal] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Kamen, Diane L.; Gilkeson, Gary S.] Med Univ S Carolina, Dept Med, Div Rheumatol, Charleston, SC 29425 USA. [Niewold, Timothy B.] Mayo Clin, Div Rheumatol, Rochester, MN USA. [Niewold, Timothy B.] Mayo Clin, Dept Immunol, Rochester, MN USA. [Merrill, Joan T.] Oklahoma Med Res Fdn, Clin Pharmacol Program, Oklahoma City, OK 73104 USA. [Scofield, R. Hal] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Criswell, Lindsey A.] Univ Calif San Francisco, Rosalind Russell Med Res Ctr Arthritis, Dept Med, San Francisco, CA 94143 USA. [Stevens, Anne M.] Univ Washington, Dept Pediat, Div Rheumatol, Seattle, WA 98195 USA. [Stevens, Anne M.] Seattle Childrens Res Inst, Ctr Immun & Immunotherapies, Seattle, WA USA. [Boackle, Susan A.] Univ Colorado, Sch Med, Div Rheumatol, Aurora, CO USA. [Pons-Estel, Bernardo A.] Sanatorio Parque, Dept Med, Rosario, Argentina. [Freedman, Barry I.] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. [Anaya, Juan-Manuel] Univ Rosario, Ctr Autoimmune Dis Res, Bogota, Colombia. [Martin, Javier] CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada, Spain. [Yu, C. Yung] Nationwide Childrens Hosp, Ctr Mol & Human Genet, Res Inst, Columbus, OH USA. [Yu, C. Yung] Ohio State Univ, Columbus, OH 43210 USA. [Chang, Deh-Ming] Natl Def Med Ctr, Taipei, Taiwan. [Song, Yeong Wook] Seoul Natl Univ, Div Rheumatol, Seoul, South Korea. [Langefeld, Carl D.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Cantor, Rita M.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA. RP Sakurai, D (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Rheumatol, Los Angeles, CA 90095 USA. EM btsao@mednet.ucla.edu RI Martin, Javier/B-8141-2008; Yu, Chack-Yung/E-4360-2011; Anaya, Juan-Manuel/J-1960-2016; OI Kimberly, Robert/0000-0002-5330-3086; Niewold, Timothy/0000-0003-3532-6660; Anaya, Juan-Manuel/0000-0002-6444-1249; Catoggio, Luis Jose/0000-0002-4047-4863; Universidad del Rosario, Biblioteca/0000-0003-3491-9392; Silva, Berta/0000-0001-6579-5068 FU US National Institutes of Health [R01AR043814, P30AR48311, R01CA141700, RC1AR058621, P01AI083194, P01AR049084, R01AR33062, K24AR002138, P602AR30692, UL1RR025741, R01AR43727, P01AR052915, U01AI090909]; Lupus Research Institute; Alliance for Lupus Research grants; U.S. Department of Defense [PR094002]; US Department of Veterans Affairs; Arthritis National Research Foundation; Charles Barkley Research Award; Ministry for Health and Welfare, Republic of Korea [A120404]; Swedish Research Council of Medicine; Arthritis Research UK; Arthritis Foundation; National Center for Advancing Translational Sciences (NCATS) [UL1RR025014-02, UL1TR000165, UL1RR025005]; National Center for Research Resources (NCRR) component of the National Institutes of Health (NIH); Kirkland Scholar Award; Federico Wilhelm Agricola Foundation; Wake Forest University Health Sciences Center for Public Health Genomics; MKE/KEIT [10035615]; UCLA Clinical and Translational Science Institute (CTSI) [UL1RR033176, UL1TR000124]; US NIH [R01AR057172, R01AI063274, RC2AR058959, R01AR043274, P30AR053483, P30GM103510, U19AI082714, U01AI101934, P60AR049459, UL1RR029882, K08AI083790, L30AI071651, UL1RR024999, P60AR053308, UL1TR000004, R01AR051545-01A2, R21AI070304, 1R01AR054459] FX Support for this work was provided by the US National Institutes of Health grants: R01AR043814 (BPT), P30AR48311 (EEB), R01CA141700 and RC1AR058621 (MEAR), P01AI083194 (JBH KMS RPK LAC TJV MEAR COJ BPT PMG), P01AR049084 (RPK JBH EEB JCE RRG LMV MAP), R01AR33062 (RPK), K24AR002138, P602AR30692 and UL1RR025741 (RRG), R01AR43727 (MAP), P01AR052915 and U01AI090909 (JDR), R01AR057172 (COJ), R01AI063274 and RC2AR058959 (PMG), R01AR043274 (KMS), P30AR053483, P30GM103510, U19AI082714 and U01AI101934 (JAJ), P60AR049459 and UL1RR029882 (GSG DLK), K08AI083790, L30AI071651 and UL1RR024999 (TBN), P60AR053308 and UL1TR000004 (LAC), R01AR051545-01A2 (AMS), R21AI070304 (SAB), and 1R01AR054459 (CYY). Additional support was provided by the Lupus Research Institute grant (BPT); the Alliance for Lupus Research grants (BPT YD KMS TBN LAC COJ); the U.S. Department of Defense PR094002 and the US Department of Veterans Affairs Merit Award (JBH); the Arthritis National Research Foundation Eng Tan Scholar Award (TBN JZ); Charles Barkley Research Award (EEB); the Korea Healthcare Technology R&D Project, Ministry for Health and Welfare, Republic of Korea (A120404; SCB); funding from the Swedish Research Council of Medicine (MEAR); the Arthritis Research UK (TJV); the Arthritis Foundation (AMS PMG); Clinical and Translational Science Grant Number UL1RR025014-02 (AMS), UL1TR000165 (JCE) and UL1RR025005 (MAP) from the National Center for Advancing Translational Sciences (NCATS) and National Center for Research Resources (NCRR) component of the National Institutes of Health (NIH); Kirkland Scholar Award (LAC); the Federico Wilhelm Agricola Foundation Research grant (BAPE); Wake Forest University Health Sciences Center for Public Health Genomics (CDL); the Korean Research and Development Program of MKE/KEIT (10035615; YWS); and UCLA Clinical and Translational Science Institute (CTSI) grants: UL1RR033176 and UL1TR000124. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 89 TC 13 Z9 13 U1 321 U2 327 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2013 VL 9 IS 10 AR e1003870 DI 10.1371/journal.pgen.1003870 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 299AR UT WOS:000330367200046 PM 24130510 ER PT J AU Soukas, AA Carr, CE Ruvkun, G AF Soukas, Alexander A. Carr, Christopher E. Ruvkun, Gary TI Genetic Regulation of Caenorhabditis elegans Lysosome Related Organelle Function SO PLOS GENETICS LA English DT Article ID C. ELEGANS; FAT STORAGE; LIFE-SPAN; LIPID DROPLETS; BIOGENESIS; SEROTONIN; MECHANISMS; KYNURENINE; MUTANTS; METABOLISM AB Lysosomes are membrane-bound organelles that contain acid hydrolases that degrade cellular proteins, lipids, nucleic acids, and oligosaccharides, and are important for cellular maintenance and protection against age-related decline. Lysosome related organelles (LROs) are specialized lysosomes found in organisms from humans to worms, and share many of the features of classic lysosomes. Defective LROs are associated with human immune disorders and neurological disease. Caenorhabditis elegans LROs are the site of concentration of vital dyes such as Nile red as well as age-associated autofluorescence. Even though certain short-lived mutants have high LRO Nile red and high autofluorescence, and other long-lived mutants have low LRO Nile red and low autofluorescence, these two biologies are distinct. We identified a genetic pathway that modulates aging-related LRO phenotypes via serotonin signaling and the gene kat-1, which encodes a mitochondrial ketothiolase. Regulation of LRO phenotypes by serotonin and kat-1 in turn depend on the proton-coupled, transmembrane transporter SKAT-1. skat-1 loss of function mutations strongly suppress the high LRO Nile red accumulation phenotype of kat-1 mutation. Using a systems approach, we further analyzed the role of 571 genes in LRO biology. These results highlight a gene network that modulates LRO biology in a manner dependent upon the conserved protein kinase TOR complex 2. The results implicate new genetic pathways involved in LRO biology, aging related physiology, and potentially human diseases of the LRO. C1 [Soukas, Alexander A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Soukas, Alexander A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Carr, Christopher E.; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Carr, Christopher E.] MIT, Dept Earth & Interplanetary Sci, Cambridge, MA 02139 USA. [Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Soukas, AA (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM asoukas@chgr.mgh.harvard.edu; ruvkun@molbio.mgh.harvard.edu OI Carr, Christopher/0000-0002-7946-5622 FU NIH/NIDDK [K08DK087941, R01DK070147]; New Scholar in Aging Award from the Ellison Medical Foundation; NIH Office of Research Infrastructure Programs [P40 OD010440] FX This work was supported by grants from the NIH/NIDDK (K08DK087941 to AAS and R01DK070147 to GR) and a New Scholar in Aging Award from the Ellison Medical Foundation (to AAS). Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 6 Z9 9 U1 1 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2013 VL 9 IS 10 AR e1003908 DI 10.1371/journal.pgen.1003908 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 299AR UT WOS:000330367200072 PM 24204312 ER PT J AU Hatano, H Yukl, SA Ferre, AL Graf, EH Somsouk, M Sinclair, E Abdel-Mohsen, M Liegler, T Harvill, K Hoh, R Palmer, S Bacchetti, P Hunt, PW Martin, JN McCune, JM Tracy, RP Busch, MP O'Doherty, U Shacklett, BL Wong, JK Deeks, SG AF Hatano, Hiroyu Yukl, Steven A. Ferre, April L. Graf, Erin H. Somsouk, Ma Sinclair, Elizabeth Abdel-Mohsen, Mohamed Liegler, Teri Harvill, Kara Hoh, Rebecca Palmer, Sarah Bacchetti, Peter Hunt, Peter W. Martin, Jeffrey N. McCune, Joseph M. Tracy, Russell P. Busch, Michael P. O'Doherty, Una Shacklett, Barbara L. Wong, Joseph K. Deeks, Steven G. TI Prospective Antiretroviral Treatment of Asymptomatic, HIV-1 Infected Controllers SO PLOS PATHOGENS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL-ACTIVATION; POLYMERASE-CHAIN-REACTION; HIV-1 ELITE CONTROLLERS; BLOOD MONONUCLEAR-CELLS; LOW-LEVEL VIREMIA; RALTEGRAVIR INTENSIFICATION; IMMUNE ACTIVATION; RECTAL MUCOSA; TYPE-1 RNA AB The study of HIV-infected "controllers'' who are able to maintain low levels of plasma HIV RNA in the absence of antiretroviral therapy (ART) may provide insights for HIV cure and vaccine strategies. Despite maintaining very low levels of plasma viremia, controllers have elevated immune activation and accelerated atherosclerosis. However, the degree to which low-level replication contributes to these phenomena is not known. Sixteen asymptomatic controllers were prospectively treated with ART for 24 weeks. Controllers had a statistically significant decrease in ultrasensitive plasma and rectal HIV RNA levels with ART. Markers of T cell activation/dysfunction in blood and gut mucosa also decreased substantially with ART. Similar reductions were observed in the subset of "elite'' controllers with pre-ART plasma HIV RNA levels below conventional assays (<40 copies/mL). These data confirm that HIV replication persists in controllers and contributes to a chronic inflammatory state. ART should be considered for these individuals (ClinicalTrials.gov NCT01025427). C1 [Hatano, Hiroyu; Yukl, Steven A.; Somsouk, Ma; Sinclair, Elizabeth; Abdel-Mohsen, Mohamed; Liegler, Teri; Harvill, Kara; Hoh, Rebecca; Hunt, Peter W.; McCune, Joseph M.; Wong, Joseph K.; Deeks, Steven G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Yukl, Steven A.; Wong, Joseph K.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Ferre, April L.; Shacklett, Barbara L.] Univ Calif Davis, Sch Med, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. [Graf, Erin H.; O'Doherty, Una] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. [Palmer, Sarah] Karolinska Inst, Solna, Sweden. [Palmer, Sarah] Swedish Inst Infect Dis Control, Solna, Sweden. [Palmer, Sarah] Westmead Millennium Inst, Ctr Virus Res, Westmead, NSW, Australia. [Palmer, Sarah] Univ Sydney, Westmead, NSW 2145, Australia. [Bacchetti, Peter; Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Tracy, Russell P.] Univ Vermont, Dept Pathol, Colchester, VT USA. [Tracy, Russell P.] Univ Vermont, Dept Biochem, Colchester, VT USA. [Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA USA. [Busch, Michael P.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. RP Hatano, H (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. EM hhatano@php.ucsf.edu RI Shacklett, Barbara/A-7288-2009 OI Shacklett, Barbara/0000-0002-7067-732X FU National Institute of Allergy and Infectious Diseases [R01 AI087145, K23 AI075985, K24 AI069994, R56 AI091573, R01 NS051132, R01 AI057020]; National Cancer Institute [K23 CA157929]; Delaney AIDS Research Enterprise (DARE) [U19 AI0961090]; California HIV/AIDS Research Program [ID08-SF-004]; American Foundation for AIDS Research [106710-40-RGRL, 107170-44-RGRL, 108073-50-RGRL]; UCSF/Gladstone Institute of Virology & Immunology CFAR [P30 AI027763]; UCSF Clinical and Translational Research Institute Clinical Research Center [UL1 RR024131]; Center for AIDS Prevention Studies [P30 MH62246]; CFAR Network of Integrated Systems [R24 AI067039]; U.S. Department of Veterans Affairs [1 IK2 CX000520-01, 5101BX001048] FX This work was supported by grants from the National Institute of Allergy and Infectious Diseases (R01 AI087145, K23 AI075985, K24 AI069994, R56 AI091573, R01 NS051132, R01 AI057020), the National Cancer Institute (K23 CA157929), the Delaney AIDS Research Enterprise (DARE; U19 AI0961090), California HIV/AIDS Research Program (ID08-SF-004), the American Foundation for AIDS Research (106710-40-RGRL, 107170-44-RGRL, and 108073-50-RGRL), the UCSF/Gladstone Institute of Virology & Immunology CFAR (P30 AI027763), the UCSF Clinical and Translational Research Institute Clinical Research Center (UL1 RR024131), the Center for AIDS Prevention Studies (P30 MH62246), the CFAR Network of Integrated Systems (R24 AI067039), and the U.S. Department of Veterans Affairs (1 IK2 CX000520-01, 5101BX001048). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 67 TC 35 Z9 35 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD OCT PY 2013 VL 9 IS 10 AR e1003691 DI 10.1371/journal.ppat.1003691 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 299GJ UT WOS:000330383800060 PM 24130489 ER PT J AU Lucas-Hourani, M Dauzonne, D Jorda, P Cousin, G Lupan, A Helynck, O Caignard, G Janvier, G Andre-Leroux, G Khiar, S Escriou, N Despres, P Jacob, Y Munier-Lehmann, H Tangy, F Vidalain, PO AF Lucas-Hourani, Marianne Dauzonne, Daniel Jorda, Pierre Cousin, Gaelle Lupan, Alexandru Helynck, Olivier Caignard, Gregory Janvier, Genevieve Andre-Leroux, Gwenaelle Khiar, Samira Escriou, Nicolas Despres, Philippe Jacob, Yves Munier-Lehmann, Helene Tangy, Frederic Vidalain, Pierre-Olivier TI Inhibition of Pyrimidine Biosynthesis Pathway Suppresses Viral Growth through Innate Immunity SO PLOS PATHOGENS LA English DT Article ID IMMUNOSUPPRESSIVE AGENT LEFLUNOMIDE; TOLL-LIKE RECEPTORS; VIRUS-INFECTION; GENE INDUCTION; RNA VIRUSES; DIHYDROOROTATE DEHYDROGENASE; ANTIVIRAL ACTIVITY; MYCOPHENOLIC-ACID; IN-VITRO; IRF-1 AB Searching for stimulators of the innate antiviral response is an appealing approach to develop novel therapeutics against viral infections. Here, we established a cell-based reporter assay to identify compounds stimulating expression of interferon-inducible antiviral genes. DD264 was selected out of 41,353 compounds for both its immuno-stimulatory and antiviral properties. While searching for its mode of action, we identified DD264 as an inhibitor of pyrimidine biosynthesis pathway. This metabolic pathway was recently identified as a prime target of broad-spectrum antiviral molecules, but our data unraveled a yet unsuspected link with innate immunity. Indeed, we showed that DD264 or brequinar, a well-known inhibitor of pyrimidine biosynthesis pathway, both enhanced the expression of antiviral genes in human cells. Furthermore, antiviral activity of DD264 or brequinar was found strictly dependent on cellular gene transcription, nuclear export machinery, and required IRF1 transcription factor. In conclusion, the antiviral property of pyrimidine biosynthesis inhibitors is not a direct consequence of pyrimidine deprivation on the virus machinery, but rather involves the induction of cellular immune response. C1 [Lucas-Hourani, Marianne; Caignard, Gregory; Janvier, Genevieve; Khiar, Samira; Escriou, Nicolas; Tangy, Frederic; Vidalain, Pierre-Olivier] Inst Pasteur, Unite Genom Virale & Vaccinat, Paris, France. [Lucas-Hourani, Marianne; Caignard, Gregory; Janvier, Genevieve; Khiar, Samira; Escriou, Nicolas; Jacob, Yves; Tangy, Frederic; Vidalain, Pierre-Olivier] CNRS, UMR3569, Paris, France. [Dauzonne, Daniel; Jorda, Pierre; Cousin, Gaelle] Inst Curie, Ctr Rech, Paris, France. [Dauzonne, Daniel; Jorda, Pierre; Cousin, Gaelle] CNRS, UMR176, Paris, France. [Lupan, Alexandru; Helynck, Olivier; Munier-Lehmann, Helene] Inst Pasteur, Unite Chim & Biocatalyse, Paris, France. [Lupan, Alexandru; Helynck, Olivier; Munier-Lehmann, Helene] CNRS, UMR3523, Paris, France. [Andre-Leroux, Gwenaelle] Inst Pasteur, Unite Biochim Struct, Paris, France. [Andre-Leroux, Gwenaelle] CNRS, UMR 3528, Paris, France. [Despres, Philippe] Inst Pasteur, Unite Interact Mol Flavivirus Hotes, Paris, France. [Jacob, Yves] Inst Pasteur, Unite Genet Mol Virus ARN, Paris, France. [Jacob, Yves] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. [Jacob, Yves] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Lucas-Hourani, M (reprint author), Inst Pasteur, Unite Genom Virale & Vaccinat, Paris, France. EM helene.munier-lehmann@pasteur.fr; frederic.tangy@pasteur.fr; pierre-olivier.vidalain@pasteur.fr RI Lupan, Alexandru/A-3142-2012; Escriou, Nicolas/A-2392-2016 OI Lupan, Alexandru/0000-0002-9353-7629; Escriou, Nicolas/0000-0002-1224-6839 FU Institut Pasteur; Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante Et de la Recherche Medicale (INSERM); Institut Carnot - Pasteur Maladies Infectieuses (Programme STING); Institut Carnot - Pasteur Maladies Infectieuses (HML); Agence Nationale pour la Recherche (ANR-RPIB, Programme STING 2.0); "Conseil Regional d'Ile-de-France'' (Chemical Library Project) [I 06-222/R, I 09-1739/R]; project ArbOAS (ANR) [2010-INTB-1601-02] FX This work was supported by the Institut Pasteur (www.pasteur.fr), the Centre National de la Recherche Scientifique (CNRS; www.cnrs.fr), the Institut National de la Sante Et de la Recherche Medicale (INSERM; www.inserm.fr), the Institut Carnot - Pasteur Maladies Infectieuses (Programme STING to POV and HML), the Agence Nationale pour la Recherche (ANR-RPIB, Programme STING 2.0 to POV), and the "Conseil Regional d'Ile-de-France'' (Chemical Library Project, grants no I 06-222/R and I 09-1739/R to HML). The work on CHIKV/Ren was supported by the project ArbOAS (ANR grant 2010-INTB-1601-02). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 72 TC 18 Z9 19 U1 1 U2 21 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD OCT PY 2013 VL 9 IS 10 AR e1003678 DI 10.1371/journal.ppat.1003678 PG 18 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 299GJ UT WOS:000330383800048 PM 24098125 ER PT J AU Matreyek, KA Yucel, SS Li, X Engelman, A AF Matreyek, Kenneth A. Yuecel, Sara S. Li, Xiang Engelman, Alan TI Nucleoporin NUP153 Phenylalanine-Glycine Motifs Engage a Common Binding Pocket within the HIV-1 Capsid Protein to Mediate Lentiviral Infectivity SO PLOS PATHOGENS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NUCLEAR-PORE COMPLEX; AMINO-TERMINAL DOMAIN; PREINTEGRATION COMPLEX; REVERSE TRANSCRIPTION; NONDIVIDING CELLS; TRIM5-ALPHA RESTRICTION; RETROTRANSPOSON TF1; TYPE-1 INFECTION; IMPORT PATHWAYS AB Lentiviruses can infect non-dividing cells, and various cellular transport proteins provide crucial functions for lentiviral nuclear entry and integration. We previously showed that the viral capsid (CA) protein mediated the dependency on cellular nucleoporin (NUP) 153 during HIV-1 infection, and now demonstrate a direct interaction between the CA N-terminal domain and the phenylalanine-glycine (FG)-repeat enriched NUP153 C-terminal domain (NUP153(C)). NUP153(C) fused to the effector domains of the rhesus Trim5 alpha restriction factor (Trim-NUP153(C)) potently restricted HIV-1, providing an intracellular readout for the NUP153(C)-CA interaction during retroviral infection. Primate lentiviruses and equine infectious anemia virus (EIAV) bound NUP153(C) under these conditions, results that correlated with direct binding between purified proteins in vitro. These binding phenotypes moreover correlated with the requirement for endogenous NUP153 protein during virus infection. Mutagenesis experiments concordantly identified NUP153(C) and CA residues important for binding and lentiviral infectivity. Different FG motifs within NUP153(C) mediated binding to HIV-1 versus EIAV capsids. HIV-1 CA binding mapped to residues that line the common alpha helix 3/4 hydrophobic pocket that also mediates binding to the small molecule PF-3450074 (PF74) inhibitor and cleavage and polyadenylation specific factor 6 (CPSF6) protein, with Asn57 (Asp58 in EIAV) playing a particularly important role. PF74 and CPSF6 accordingly each competed with NUP153(C) for binding to the HIV-1 CA pocket, and significantly higher concentrations of PF74 were needed to inhibit HIV-1 infection in the face of Trim-NUP153(C) expression or NUP153 knockdown. Correlation between CA mutant viral cell cycle and NUP153 dependencies moreover indicates that the NUP153(C)-CA interaction underlies the ability of HIV-1 to infect non-dividing cells. Our results highlight similar mechanisms of binding for disparate host factors to the same region of HIV-1 CA during viral ingress. We conclude that a subset of lentiviral CA proteins directly engage FG-motifs present on NUP153 to affect viral nuclear import. C1 [Matreyek, Kenneth A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Matreyek, KA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu OI Matreyek, Kenneth/0000-0001-9149-551X FU US National Institutes of Health [AI052014] FX US National Institutes of Health grant AI052014 provided the funding to support this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 90 TC 55 Z9 57 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD OCT PY 2013 VL 9 IS 10 AR e1003693 DI 10.1371/journal.ppat.1003693 PG 21 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 299GJ UT WOS:000330383800062 PM 24130490 ER PT J AU Mehra, A Zahra, A Thompson, V Sirisaengtaksin, N Wells, A Porto, M Koster, S Penberthy, K Kubota, Y Dricot, A Rogan, D Vidal, M Hill, DE Bean, AJ Philips, JA AF Mehra, Alka Zahra, Aleena Thompson, Victor Sirisaengtaksin, Natalie Wells, Ashley Porto, Maura Koester, Stefan Penberthy, Kristen Kubota, Yoshihisha Dricot, Amelie Rogan, Daniel Vidal, Marc Hill, David E. Bean, Andrew J. Philips, Jennifer A. TI Mycobacterium tuberculosis Type VII Secreted Effector EsxH Targets Host ESCRT to Impair Trafficking SO PLOS PATHOGENS LA English DT Article ID RECEPTOR DOWN-REGULATION; NF-KAPPA-B; PHAGOSOME MATURATION; COMPLEX-FORMATION; EGF RECEPTOR; LIPOAMIDE DEHYDROGENASE; HRS PROTEIN; BOVIS BCG; FAMILY; SYSTEM AB Mycobacterium tuberculosis (Mtb) disrupts anti-microbial pathways of macrophages, cells that normally kill bacteria. Over 40 years ago, D'Arcy Hart showed that Mtb avoids delivery to lysosomes, but the molecular mechanisms that allow Mtb to elude lysosomal degradation are poorly understood. Specialized secretion systems are often used by bacterial pathogens to translocate effectors that target the host, and Mtb encodes type VII secretion systems (TSSSs) that enable mycobacteria to secrete proteins across their complex cell envelope; however, their cellular targets are unknown. Here, we describe a systematic strategy to identify bacterial virulence factors by looking for interactions between the Mtb secretome and host proteins using a high throughput, high stringency, yeast two-hybrid (Y2H) platform. Using this approach we identified an interaction between EsxH, which is secreted by the Esx-3 TSSS, and human hepatocyte growth factor-regulated tyrosine kinase substrate (Hgs/Hrs), a component of the endosomal sorting complex required for transport (ESCRT). ESCRT has a well-described role in directing proteins destined for lysosomal degradation into intraluminal vesicles (ILVs) of multivesicular bodies (MVBs), ensuring degradation of the sorted cargo upon MVB-lysosome fusion. Here, we show that ESCRT is required to deliver Mtb to the lysosome and to restrict intracellular bacterial growth. Further, EsxH, in complex with EsxG, disrupts ESCRT function and impairs phagosome maturation. Thus, we demonstrate a role for a TSSS and the host ESCRT machinery in one of the central features of tuberculosis pathogenesis. C1 [Mehra, Alka; Zahra, Aleena; Thompson, Victor; Wells, Ashley; Porto, Maura; Koester, Stefan; Penberthy, Kristen; Rogan, Daniel; Philips, Jennifer A.] NYU, Sch Med, Dept Med, Dept Pathol,Div Infect Dis, New York, NY 10012 USA. [Mehra, Alka; Zahra, Aleena; Thompson, Victor; Wells, Ashley; Porto, Maura; Koester, Stefan; Penberthy, Kristen; Rogan, Daniel; Philips, Jennifer A.] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA. [Sirisaengtaksin, Natalie; Kubota, Yoshihisha; Bean, Andrew J.] Univ Texas Hlth Sci Ctr Houston, Dept Neurobiol & Anat, Houston, TX 77030 USA. [Sirisaengtaksin, Natalie; Kubota, Yoshihisha; Bean, Andrew J.] Univ Texas Hlth Sci Ctr Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA. [Dricot, Amelie; Vidal, Marc; Hill, David E.] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. [Dricot, Amelie; Vidal, Marc; Hill, David E.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Dricot, Amelie; Vidal, Marc; Hill, David E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Bean, Andrew J.] Univ Texas MD Anderson Canc Ctr, Div Pediat, Houston, TX 77030 USA. RP Mehra, A (reprint author), NYU, Sch Med, Dept Med, Dept Pathol,Div Infect Dis, New York, NY 10012 USA. EM Jennifer.Philips@nyumc.org OI Sirisaengtaksin, Natalie/0000-0002-8791-722X; Penberthy, Kristen/0000-0003-3178-0524 FU NIH/NIAID [AI087682]; Doris Duke Charitable Foundation; Infectious Disease Society of America (IDSA); Michael Saperstein Medical Scholars Research Fund; NIH [HG004233, HG001715]; Ellison Foundation (Boston, MA); Institute Sponsored Research funds from the Dana-Farber Cancer Institute Strategic Initiative; DEH Potts Memorial Foundation; American Society of Microbiology; IDSA FX This work was supported by grants from the NIH/NIAID (AI087682), the Doris Duke Charitable Foundation, the Infectious Disease Society of America (IDSA), and the Michael Saperstein Medical Scholars Research Fund to JAP. It was supported by NIH (HG004233 and HG001715), Ellison Foundation (Boston, MA), and Institute Sponsored Research funds from the Dana-Farber Cancer Institute Strategic Initiative to MV and DEH Potts Memorial Foundation provided support to AM, IDSA provided support to MP, and the American Society of Microbiology supported AZ. http://www.ddcf.org http://www.idsociety.org/Index.aspx http://www.ellisonfoundation.org http://www.asm.org http://www.dana-farber.org Pott's and Michael Saperstein Fund: URL not available. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript NR 67 TC 33 Z9 35 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD OCT PY 2013 VL 9 IS 10 AR e1003734 DI 10.1371/journal.ppat.1003734 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 299GJ UT WOS:000330383800092 PM 24204276 ER PT J AU Rollman, BL Huffman, JC AF Rollman, Bruce L. Huffman, Jeff C. TI Treating Anxiety in the Presence of Medical Comorbidity: Calmly Moving Forward SO PSYCHOSOMATIC MEDICINE LA English DT Editorial Material DE chronic medical conditions; depression; anxiety; collaborative care; interventions ID RANDOMIZED CONTROLLED-TRIAL; COLLABORATIVE CARE; DEPRESSION; DISORDERS; QUALITY AB Patients with chronic medical conditions (CMCs) and a comorbid anxiety or mood disorder tend to report more symptoms and experience poorer treatment outcomes compared with those without mental health comorbidity. Although the benefits to be derived from treating depression in patients with CMCs have begun to be quantified, particularly among those with cardiovascular disease, our understanding of the benefits of treating anxiety in patients with CMCs is far less developed. Improving care for patients with CMCs is one of the major challenges facing medicine today because patients with multiple chronic diseases account for most health care costs. Emerging evidence indicates that integrated or "blended" collaborative care strategies that treat both the psychiatric and physical conditions together tend to produce greater improvements in mood symptoms and control of CMCs compared with programs that target the psychiatric condition alone. We review a new report, published in this issue of Psychosomatic Medicine, from the National Institutes of Mental Health-funded multisite Coordinated Anxiety Learning and Management trial, that shines new attention on anxiety disorders and medical comorbidity. We place their findings in context with these new blended care models that are potentially more powerful, scalable, cost-effective, and readily delivered through existing CMC programs. C1 [Rollman, Bruce L.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. [Huffman, Jeff C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Psychiat & Med, Boston, MA USA. RP Rollman, BL (reprint author), Univ Pittsburgh, Sch Med, Div Gen Internal Med, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. FU NHLBI NIH HHS [R01 HL114016, 1R01HL113272]; NIMH NIH HHS [R01 MH093501] NR 15 TC 3 Z9 3 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD OCT PY 2013 VL 75 IS 8 BP 710 EP 712 DI 10.1097/PSY.0000000000000011 PG 3 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 300MZ UT WOS:000330469300001 PM 24096773 ER PT J AU Feldt, B Dion, GR Weitzel, EK McMains, KC AF Feldt, Brent Dion, Gregory R. Weitzel, Erik K. McMains, Kevin C. TI Acute Sinusitis SO SOUTHERN MEDICAL JOURNAL LA English DT Review DE acute sinusitis; bacterial sinusitis; nasal airway obstruction; purulent rhinorrhea; sinusitis ID ACUTE BACTERIAL RHINOSINUSITIS; ANTIMICROBIAL THERAPY; CONTROLLED TRIAL; DOUBLE-BLIND; ADULTS; METAANALYSIS; ANTIBIOTICS; AMOXICILLIN; DIAGNOSIS; RHINITIS AB Sinusitis is a common patient complaint that carries with it a large economic burden. It is one of the most common reasons patients visit their primary care physician. Acute bacterial rhinosinusitis (ABRS) can be distinguished from other forms of rhinosinusitis based on symptom duration of <4 weeks in a patient with purulent rhinorrhea associated with facial pain or pressure. Native upper aerodigestive tract bacteria are the most common etiologic agents. Treatment of ABRS is targeted primarily at symptom improvement. Amoxicillin can be used based on the clinical scenario and patient comorbidities. Computed tomographic scans are reserved for complicated presentations or when there is concern for intracranial extension or other complications. A systematic approach to ABRS will allow for improved patient quality of life and a decreased overall economic burden of this common entity. C1 Wilford Hall Ambulatory Surg Ctr, San Antonio, TX USA. Brooke Army Med Ctr, San Antonio Mil Med Ctr, Ft Sam Houston, TX 78234 USA. Audie L Murphy Mem Vet Adm Med Ctr, South Texas Vet Hlth Care, San Antonio, TX 78284 USA. RP Dion, GR (reprint author), ATTN MCHE SDT Oto, Dept Otolaryngol, 3551 Roger Brooke Dr, Ft Sam Houston, TX 78234 USA. EM greg.r.dion@us.army.mil NR 32 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 EI 1541-8243 J9 SOUTH MED J JI South.Med.J. PD OCT PY 2013 VL 106 IS 10 BP 577 EP 581 DI 10.1097/SMJ.0000000000000002 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 298UK UT WOS:000330349800007 PM 24096952 ER PT J AU Reisenbichler, ES Lester, SC Richardson, AL Dillon, DA Ly, A Brock, JE AF Reisenbichler, Emily S. Lester, Susan C. Richardson, Andrea L. Dillon, Deborah A. Ly, Amy Brock, Jane E. TI lnterobserver Concordance in Implementing the 2010 ASCO/CAP Recommendations for Reporting ER in Breast Carcinomas A Demonstration of the Difficulties of Consistently Reporting Low Levels of ER Expression by Manual Quantification SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Estrogen receptor; Immunohistochemistry; Concordance; Breast carcinoma ID ESTROGEN-RECEPTOR STATUS; LIGAND-BINDING ASSAY; PROGESTERONE-RECEPTOR; PREDICTING RESPONSE; CANCER; IMMUNOHISTOCHEMISTRY; TAMOXIFEN; SURVIVAL; THERAPY; RECURRENCE AB Objectives: Endocrine therapy reduces recurrence risk by 30% to 50% in estrogen receptor (ER) positive breast cancer. The ER-positive threshold recommended by the American Society of Clinical Oncology/College of American Pathologists is 1% based on studies using the ER-6F11 antibody. ER-SP1 antibody has a higher sensitivity and is more widely used. Methods: We report interobserver concordance manually measuring ER in 264 breast cancers using ER-SP1 and 1D5 and 2 scoring methods (H-score and Allred score). Results: With both antibodies, 3% to 4% of cases have a low level of ER expression (1%-10%), more than previously reported (<1%). We find a high level of paired observer concordance with both antibodies and scoring methods (K = 0.892-0.943) with no significant difference with method of scoring. Despite excellent concordance, positive/negative discordance was almost 5% among 3 observers using either antibody, an underappreciated clinically significant rate. Conclusions: Discordance overwhelmingly reflected differing opinions recording the proportion of tumor cells positive with low levels of expression (<10% staining; 12/13 cases). C1 [Reisenbichler, Emily S.; Lester, Susan C.; Richardson, Andrea L.; Dillon, Deborah A.; Brock, Jane E.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ly, Amy] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reisenbichler, ES (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, MCN C-3321,1161 21st Ave S, Nashville, TN 37232 USA. EM Emily.s.reisenbiehler@vanderbilt.edu NR 20 TC 11 Z9 12 U1 0 U2 1 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD OCT PY 2013 VL 140 IS 4 BP 487 EP 494 DI 10.1309/AJCP1RF9FUIZRDPI PG 8 WC Pathology SC Pathology GA 295EQ UT WOS:000330099800004 PM 24045544 ER PT J AU Muehlschlegel, S Kursun, O Topcuoglu, MA Fok, J Singhal, AB AF Muehlschlegel, Susanne Kursun, Oguzhan Topcuoglu, Mehmet A. Fok, Joshua Singhal, Aneesh B. TI Differentiating Reversible Cerebral Vasoconstriction Syndrome With Subarachnoid Hemorrhage From Other Causes of Subarachnoid Hemorrhage SO JAMA NEUROLOGY LA English DT Article ID INTRACRANIAL ANEURYSMS; CLINICAL PRESENTATION; ANGIOGRAPHY; VASOSPASM; RISK; MANAGEMENT; HEADACHE; TIME AB IMPORTANCE Reversible cerebral vasoconstriction syndrome (RCVS) is a clinical-angiographic syndrome characterized by recurrent thunderclap headaches and reversible segmental multifocal cerebral artery narrowing. More than 30% of patients with RCVS develop subarachnoid hemorrhage (SAH). Patients with RCVS with SAH (RCVS-SAH) are often misdiagnosed as having potentially ominous conditions such as aneurysmal SAH (aSAH) or cryptogenic "angiogram-negative" SAH (cSAH) owing to overlapping clinical and imaging features. OBJECTIVE To identify predictors that can distinguish RCVS-SAH from aSAH and cSAH at the time of clinical presentation. DESIGN Retrospective analysis of 3 patient cohorts: patients with RCVS (1998-2009), patients with aSAH (1995-2003), and patients with cSAH (1995-2003). SETTING Academic hospital and tertiary referral center. PARTICIPANTS Consecutive patients with RCVS-SAH (n = 38), aSAH (n = 515), or cSAH (n = 93) whose conditions were diagnosed using standard criteria. MAIN OUTCOMES AND MEASURES Multivariate logistic regression analysis was used to identify predictors that differentiate RCVS-SAH from aSAH and cSAH. RESULTS Predictors differentiating RCVS-SAH from aSAH were younger age, chronic headache disorder, prior depression, prior chronic obstructive pulmonary disease, lower Hunt-Hess grade, lower Fisher SAH group, higher number of affected arteries, and the presence of bilateral arterial narrowing. Predictors differentiating RCVS-SAH from cSAH were younger age, female sex, prior hypertension, chronic headache disorder, lower Hunt-Hess grade, lower Fisher SAH group, and the presence of bilateral arterial narrowing. CONCLUSION AND RELEVANCE We identified important clinical and imaging differences between RCVS-SAH, aSAH, and cSAH that may be useful for improving diagnostic accuracy, clinical management, and resource utilization. C1 [Muehlschlegel, Susanne] Univ Massachusetts, Sch Med, Dept Neurol, Div Neurocrit Care, Worcester, MA USA. [Muehlschlegel, Susanne] Univ Massachusetts, Sch Med, Dept Anesthesia Crit Care, Worcester, MA USA. [Muehlschlegel, Susanne] Univ Massachusetts, Sch Med, Dept Surg, Worcester, MA USA. [Kursun, Oguzhan; Singhal, Aneesh B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv, Boston, MA 02114 USA. [Topcuoglu, Mehmet A.] Hacettepe Univ, Dept Neurol, Ankara, Turkey. [Fok, Joshua] Chinese Univ Hong Kong, Dept Neurol, Hong Kong, Hong Kong, Peoples R China. RP Singhal, AB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv, ACC-729-C,55 Fruit St, Boston, MA 02114 USA. EM asinghal@partners.org FU American Heart Association [09SDG2030022]; Worcester Research Foundation; University of Massachusetts Medical School FX This work was funded in part by the American Heart Association (grant 09SDG2030022 to Dr Muehlschlegel), the Worcester Research Foundation, and the University of Massachusetts Medical School (Faculty Scholar Award to Dr Muehlschlegel). NR 27 TC 8 Z9 9 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD OCT PY 2013 VL 70 IS 10 BP 1254 EP 1260 DI 10.1001/jamaneurol.2013.3484 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 295KG UT WOS:000330114400008 PM 23939614 ER PT J AU van der Wilden, GM Velmahos, GC Joseph, DK Jacobs, L DeBusk, G Adams, CA Gross, R Burkott, B Agarwal, S Maung, AA Johnson, DC Gates, J Kelly, E Michaud, Y Charash, WE Winchell, RJ Desjardins, SE Rosenblatt, MS Gupta, S Gaeta, M Chang, YC de Moya, MA AF van der Wilden, Gwendolyn M. Velmahos, George C. Joseph, D'Andrea K. Jacobs, Lenworth DeBusk, George Adams, Charles A. Gross, Ronald Burkott, Barbara Agarwal, Suresh Maung, Adrian A. Johnson, Dirk C. Gates, Jonathan Kelly, Edward Michaud, Yvonne Charash, William E. Winchell, Robert J. Desjardins, Steven E. Rosenblatt, Michael S. Gupta, Sanjay Gaeta, Miguel Chang, Yuchiao de Moya, Marc A. TI Successful Nonoperative Management of the Most Severe Blunt Renal Injuries A Multicenter Study of the Research Consortium of New England Centers for Trauma SO JAMA SURGERY LA English DT Article ID URINARY EXTRAVASATION; CONSERVATIVE MANAGEMENT; LACERATIONS; KIDNEY; COMPLICATIONS; RECONECT; OUTCOMES; SPLEEN; LIVER AB IMPORTANCE Severe renal injuries after blunt trauma cause diagnostic and therapeutic challenges for the treating clinicians. The need for an operative vs a nonoperative approach is debated. OBJECTIVE To determine the rate, causes, predictors, and consequences of failure of nonoperative management (NOM) in grade IV and grade V blunt renal injuries (BRIs). DESIGN Retrospective case series. SETTING Twelve level I and II trauma centers in New England. PARTICIPANTS A total of 206 adult patients with a grade IV or V BRI who were admitted between January 1, 2000, and December 31, 2011. MAIN OUTCOMES AND MEASURES Failure of NOM, defined as the need for a delayed operation or death due to renal-related complications during NOM. RESULTS Of 206 patients, 52 (25.2%) were operated on immediately, and 154 (74.8%) were managed nonoperatively (with the assistance of angiographic embolization for 25 patients). Nonoperative management failed for 12 of the 154 patients (7.8%) and was related to kidney injury in 10 (6.5%). None of these 10 patients had complications because of the delay in BRI management. The mean (SD) time from admission to failure was 17.6 (27.4) hours (median time, 7.5 hours; range, 4.5-102 hours), and the cause was hemodynamic instability in 10 of the 12 patients (83.3%). Multivariate analysis identified 2 independent predictors of NOM failure: older than 55 years of age and a road traffic crash as the mechanism of injury. When both risk factors were present, NOM failure occurred for 27.3% of the patients; when both were absent, there were no NOM failures. Of the 142 patients successfully managed nonoperatively, 46 (32.4%) developed renal-related complications, including hematuria (24 patients), urinoma (15 patients), urinary tract infection (8 patients), renal failure (7 patients), and abscess (2 patients). These patients were managed successfully with no loss of renal units (ie, kidneys). The renal salvage rate was 76.2% for the entire population and 90.3% among patients selected for NOM. CONCLUSIONS AND RELEVANCE Hemodynamically stable patients with a grade IV or V BRI were safely managed nonoperatively. Nonoperative management failed for only 6.5% of patients owing to renal-related injuries, and three-fourths of the entire population retained their kidneys. C1 [van der Wilden, Gwendolyn M.; Velmahos, George C.; de Moya, Marc A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [van der Wilden, Gwendolyn M.; Velmahos, George C.; Gates, Jonathan; Kelly, Edward; Michaud, Yvonne; de Moya, Marc A.] Harvard Univ, Sch Med, Boston, MA USA. [Joseph, D'Andrea K.; Jacobs, Lenworth] Univ Connecticut, Hartford Hosp, Dept Surg, Hartford, CT 06112 USA. [DeBusk, George; Adams, Charles A.] Brown Univ, Rhode Isl Hosp, Dept Surg, Providence, RI 02903 USA. [DeBusk, George; Adams, Charles A.] Brown Univ, Providence, RI 02912 USA. [Gross, Ronald; Burkott, Barbara] Baystate Med Ctr, Dept Surg, Springfield, MA 01107 USA. [Agarwal, Suresh] Boston Med Ctr, Dept Surg, Boston, MA USA. [Agarwal, Suresh] Boston Univ, Boston, MA 02215 USA. [Maung, Adrian A.; Johnson, Dirk C.] Yale New Haven Med Ctr, Dept Surg, New Haven, CT 06504 USA. [Maung, Adrian A.; Johnson, Dirk C.] Yale Univ, Sch Med, New Haven, CT USA. [Gates, Jonathan; Kelly, Edward; Michaud, Yvonne] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Charash, William E.] Univ Vermont, Coll Med, Dept Surg, Burlington, VT USA. [Winchell, Robert J.; Desjardins, Steven E.] Maine Med Ctr, Dept Surg, Portland, ME 04102 USA. [Rosenblatt, Michael S.] Lahey Clin Fdn, Dept Surg, Burlington, MA USA. [Gupta, Sanjay] Southern New Hampshire Med Ctr, Dept Surg, Nashua, NH USA. [Gaeta, Miguel] Elliot Hosp, Dept Surg, Manchester, NH USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Dept Surg, 165 Cambridge St,Ste 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 39 TC 12 Z9 13 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD OCT PY 2013 VL 148 IS 10 BP 924 EP 931 DI 10.1001/jamasurg.2013.2747 PG 8 WC Surgery SC Surgery GA 295KL UT WOS:000330114900005 PM 23945834 ER PT J AU Hwabejire, JO Kaafarani, HMA Imam, AM Solis, CV Verge, J Sullivan, NM DeMoya, MA Alam, HB Velmahos, GC AF Hwabejire, John O. Kaafarani, Haytham M. A. Imam, Ayesha M. Solis, Carolina V. Verge, Justin Sullivan, Nancy M. DeMoya, Marc A. Alam, Hasan B. Velmahos, George C. TI Excessively Long Hospital Stays After Trauma Are Not Related to the Severity of Illness Let's Aim to the Right Target! SO JAMA SURGERY LA English DT Article ID CORONARY-BYPASS SURGERY; LENGTH-OF-STAY; ADVERSE EVENTS; CARE; VARIABILITY; COST; RISK AB IMPORTANCE Reduction in length of hospital stay is a veritable target in reducing the overall costs of health care. However, many existing approaches are flawed because the assumptions of what cause excessive length of stay are incorrect; we methodically identified the right targets in this study. OBJECTIVE To identify the causes of excessively prolonged hospitalization (ExProH) in trauma patients. DESIGN The trauma registry, billing databases, and medical records of trauma admissions were reviewed. Excessively prolonged hospitalization was defined by the standard method used by insurers, which is a hospital stay that exceeds the Diagnosis Related Group-based trim point. The causes of ExProH were explored in a unique potentially avoidable days database, used by our hospital's case managers to track discharge delays. SETTING Level I academic trauma center. PARTICIPANTS Adult trauma patients admitted between January 1, 2006, and December 31, 2010. MAIN OUTCOMES AND MEASURES Excessively prolonged hospitalization and hospital cost. RESULTS Of 3237 patients, 155 (5%) had ExProH. The patients with ExProH compared with non-ExProH patients were older (mean [SD] age, 53 [21] vs 47 [22] years, respectively; P = .001), were more likely to have blunt trauma (92% vs 84%, respectively; P = .03), were more likely to be self-payers (16% vs 11%, respectively; P = .02) or covered by Medicare/Medicaid (41% vs 30%, respectively; P = .002), were more likely to be discharged to post-acute care facilities than home (65% vs 35%, respectively; P < .001), and had higher hospitalization cost (mean, $54 646 vs $18 444, respectively; P < .001). Both groups had similar Injury Severity Scores, Revised Trauma Scores, baseline comorbidities, and in-hospital complication rates. Independent predictors of mortality were discharge to a rehabilitation facility (odds ratio = 4.66; 95% CI, 2.71-8.00; P < .001) or other post-acute care facility (odds ratio = 5.04; 95% CI, 2.52-10.05; P < .001) as well as insurance type that was Medicare/Medicaid (odds ratio = 1.70; 95% CI, 1.06-2.72; P = .03) or self-pay (odds ratio = 2.43; 95% CI, 1.35-4.37; P = .003). The reasons for discharge delays were clinical in only 20% of the cases. The remaining discharges were excessively delayed because of difficulties in rehabilitation facility placement (47%), in-hospital operational delays (26%), or payer-related issues (7%). CONCLUSIONS AND RELEVANCE System-related issues, not severity of illness, prolong hospital stay excessively. Cost-reduction efforts should target operational bottlenecks between acute and postacute care. C1 [Hwabejire, John O.; Kaafarani, Haytham M. A.; Imam, Ayesha M.; Solis, Carolina V.; Verge, Justin; DeMoya, Marc A.; Alam, Hasan B.; Velmahos, George C.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Hwabejire, John O.; Kaafarani, Haytham M. A.; Imam, Ayesha M.; Solis, Carolina V.; Verge, Justin; Sullivan, Nancy M.; DeMoya, Marc A.; Alam, Hasan B.; Velmahos, George C.] Harvard Univ, Sch Med, Boston, MA USA. [Sullivan, Nancy M.] Massachusetts Gen Hosp, Case Management Dept, Boston, MA 02114 USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Ste 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 20 TC 13 Z9 13 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD OCT PY 2013 VL 148 IS 10 BP 956 EP 961 DI 10.1001/jamasurg.2013.2148 PG 6 WC Surgery SC Surgery GA 295KL UT WOS:000330114900010 PM 23965602 ER PT J AU Ravicz, ME Rosowski, JJ AF Ravicz, Michael E. Rosowski, John J. TI Middle-ear velocity transfer function, cochlear input immittance, and middle-ear efficiency in chinchilla SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID EXTERNAL-EAR; STAPES VELOCITY; DIFFUSE FIELD; IMPEDANCE; ADMITTANCE; PRESSURE; GERBIL; CAT; TRANSMISSION; MOTION AB The transfer function H-V between stapes velocity V-S and sound pressure near the tympanic membrane P-TM is a descriptor of sound transmission through the middle ear (ME). The ME power transmission efficiency (MEE), the ratio of sound power entering the cochlea to power entering the middle ear, was computed from H-V measured in seven chinchilla ears and previously reported measurements of ME input admittance Y-TM and ME pressure gain G(MEP) [Ravicz and Rosowski, J. Acoust. Soc. Am. 132, 2437-2454 (2012); J. Acoust. Soc. Am. 133, 2208-2223 (2013)] in the same ears. The ME was open, and a pressure sensor was inserted into the cochlear vestibule for most measurements. The cochlear input admittance Y-C computed from H-V and G(MEP) is controlled by a combination of mass and resistance and is consistent with a minimum-phase system up to 27 kHz. The real part Re{Y-C}, which relates cochlear sound power to inner-ear sound pressure, decreased gradually with frequency up to 25 kHz and more rapidly above that. MEE was about 0.5 between 0.1 and 8 kHz, higher than previous estimates in this species, and decreased sharply at higher frequencies. (C) 2013 Acoustical Society of America. C1 [Ravicz, Michael E.; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Ravicz, Michael E.; Rosowski, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Rosowski, John J.] MA Inst Technol, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Ravicz, ME (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM mike_ravicz@meei.harvard.edu FU NIDCD FX We thank Michael Slama for helpful discussions, Melissa McKinnon for animal surgery and assistance with experiments, and the staff of the Eaton-Peabody Laboratory for technical support. Supported by NIDCD. NR 39 TC 6 Z9 6 U1 0 U2 4 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD OCT PY 2013 VL 134 IS 4 BP 2852 EP 2865 DI 10.1121/1.4818745 PG 14 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 295MH UT WOS:000330119700040 PM 24116422 ER PT J AU Louapre, C Govindarajan, ST Gianni, C Cohen-Adad, J Tobyne, SM Kinkel, RP Mainero, C AF Louapre, C. Govindarajan, S. T. Gianni, C. Cohen-Adad, J. Tobyne, S. M. Kinkel, R. P. Mainero, C. TI Intracortical laminar pathology in the motor cortex is associated with proximal underlying white matter injury in multiple sclerosis: a multimodal 7 T and 3 T MRI study SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 29th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis / 18th Annual Conference of Rehabilitation in MS CY OCT 02-05, 2013 CL Copenhagen, DENMARK SP European Comm Treatment & Res Multiple Sclerosis C1 [Louapre, C.; Govindarajan, S. T.; Gianni, C.; Mainero, C.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Cohen-Adad, J.] Ecole Polytech, Montreal, PQ H3C 3A7, Canada. [Tobyne, S. M.] Massachusetts Gen Hosp, Charlestown, MA USA. [Kinkel, R. P.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD OCT PY 2013 VL 19 IS 11 SU S BP 8 EP 8 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 276LI UT WOS:000328751400002 ER PT J AU Bove, R Musallam, A Healy, BC Radhavan, K Glanz, BI Weiner, H De Jager, PL Miller, KK Chitnis, T AF Bove, R. Musallam, A. Healy, B. C. Radhavan, K. Glanz, B. I. Weiner, H. De Jager, P. L. Miller, K. K. Chitnis, T. TI Testosterone is associated with worse disease severity in men with early relapsing onset multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 29th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis / 18th Annual Conference of Rehabilitation in MS CY OCT 02-05, 2013 CL Copenhagen, DENMARK SP European Comm Treatment & Res Multiple Sclerosis C1 [Bove, R.; Musallam, A.; Healy, B. C.; Radhavan, K.; Glanz, B. I.; Weiner, H.; De Jager, P. L.; Chitnis, T.] Partners Multiple Sclerosis Ctr, Brookline, MA USA. [Miller, K. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD OCT PY 2013 VL 19 IS 11 SU S BP 110 EP 110 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 276LI UT WOS:000328751401074 ER PT J AU Tobyne, S Klawiter, E Boratyn, D Govindarajan, ST Sepulcre, J Buckner, R Kinkel, RP Rosen, B Mainero, C AF Tobyne, S. Klawiter, E. Boratyn, D. Govindarajan, S. T. Sepulcre, J. Buckner, R. Kinkel, R. P. Rosen, B. Mainero, C. TI Local and distant functional connectivity changes vary based on functional network in multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 29th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis / 18th Annual Conference of Rehabilitation in MS CY OCT 02-05, 2013 CL Copenhagen, DENMARK SP European Comm Treatment & Res Multiple Sclerosis C1 [Tobyne, S.; Klawiter, E.; Boratyn, D.; Govindarajan, S. T.; Sepulcre, J.; Rosen, B.; Mainero, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Buckner, R.] Harvard Univ, Cambridge, MA 02138 USA. [Kinkel, R. P.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD OCT PY 2013 VL 19 IS 11 SU S BP 174 EP 174 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 276LI UT WOS:000328751401205 ER PT J AU Vassilev, Z Li, L Falcone, G Wallander, MA Jick, S Bromley, S AF Vassilev, Z. Li, L. Falcone, G. Wallander, M. -A. Jick, S. Bromley, S. TI Mortality and risk factors for death in patients with multiple sclerosis in a large population-based cohort SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 29th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis / 18th Annual Conference of Rehabilitation in MS CY OCT 02-05, 2013 CL Copenhagen, DENMARK SP European Comm Treatment & Res Multiple Sclerosis C1 [Vassilev, Z.] Bayer Healthcare Pharmaceut, Montville, NJ USA. [Li, L.; Jick, S.] Boston Univ, Sch Publ Hlth, Lexington, MA USA. [Falcone, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Falcone, G.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Wallander, M. -A.] Bayer AB, Solna, Sweden. [Wallander, M. -A.] Uppsala Univ, Solna, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD OCT PY 2013 VL 19 IS 11 SU S BP 343 EP 344 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 276LI UT WOS:000328751402210 ER PT J AU Bove, R Musallam, A Healy, BC Soltany, P Messina, S Glanz, BI Kivisakk, P Weiner, H De Jager, PL Miller, KK Chitnis, T AF Bove, R. Musallam, A. Healy, B. C. Soltany, P. Messina, S. Glanz, B. I. Kivisakk, P. Weiner, H. De Jager, P. L. Miller, K. K. Chitnis, T. TI Adiposity markers are associated with disease severity in early relapsing remitting multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 29th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis / 18th Annual Conference of Rehabilitation in MS CY OCT 02-05, 2013 CL Copenhagen, DENMARK SP European Comm Treatment & Res Multiple Sclerosis C1 [Bove, R.; Musallam, A.; Healy, B. C.; Glanz, B. I.; Weiner, H.; De Jager, P. L.; Chitnis, T.] Partners Multiple Sclerosis Ctr, Brookline, MA USA. [Soltany, P.; Kivisakk, P.] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. [Messina, S.] Univ Catania, Catania, Italy. [Miller, K. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD OCT PY 2013 VL 19 IS 11 SU S BP 404 EP 405 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 276LI UT WOS:000328751402336 ER PT J AU Mainero, C Govindarajan, ST Cohen-Adad, J Louapre, C Gianni', C Nielsen, AS Kinkel, RP AF Mainero, C. Govindarajan, S. T. Cohen-Adad, J. Louapre, C. Gianni', C. Nielsen, A. S. Kinkel, R. P. TI A gradient in intracortical laminar pathology in multiple sclerosis: an in vivo study at 7 Tesla MRI SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 29th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis / 18th Annual Conference of Rehabilitation in MS CY OCT 02-05, 2013 CL Copenhagen, DENMARK SP European Comm Treatment & Res Multiple Sclerosis C1 [Mainero, C.; Govindarajan, S. T.; Louapre, C.; Gianni', C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Cohen-Adad, J.] Ecole Polytech, Montreal, PQ H3C 3A7, Canada. [Nielsen, A. S.] Oregon Med Ctr, Portland, ME USA. [Kinkel, R. P.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD OCT PY 2013 VL 19 IS 11 SU S BP 429 EP 429 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 276LI UT WOS:000328751402383 ER PT J AU Mrejen, S Sarraf, D Mukkamala, K Freund, KB AF Mrejen, Sarah Sarraf, David Mukkamala, Krishna Freund, K. Bailey TI MULTIMODAL IMAGING OF PIGMENT EPITHELIAL DETACHMENT A Guide to Evaluation SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Review DE retinal pigment epithelial detachment; age-related macular degeneration; drusenoid pigment epithelial detachment; serous pigment epithelial detachment; vascularized pigment epithelial detachment; retinal angiomatous proliferation; polypoidal choroidal vasculopathy; multimodal imaging; central serous chorioretinopathy ID CENTRAL SEROUS CHORIORETINOPATHY; OPTICAL COHERENCE TOMOGRAPHY; RETINAL ANGIOMATOUS PROLIFERATION; POLYPOIDAL CHOROIDAL VASCULOPATHY; INDOCYANINE-GREEN VIDEOANGIOGRAPHY; COMBINED INTRAVITREAL RANIBIZUMAB; SCANNING LASER OPHTHALMOSCOPE; GROWTH-FACTOR THERAPY; TERM-FOLLOW-UP; MACULAR DEGENERATION AB Purpose: To describe the spectrum of pigment epithelial detachments (PEDs) occurring mainly in age-related macular degeneration and central serous chorioretinopathy and also in other inflammatory, neoplastic and iatrogenic, retinal, and systemic disorders. Methods: Pigment epithelial detachments are divided into drusenoid, serous, vascularized, or mixed categories. Results: The clinical presentation, classification, and natural history of PEDs are reviewed as illustrated with multimodal imaging combining traditional and novel imaging techniques, including fluorescein angiography, indocyanine green angiography, fundus autofluorescence, and spectral domain optical coherence tomography. Most PEDs occur because of pathophysiologic mechanisms taking place below the retinal pigment epithelium that are difficult to identify with conventional imaging modalities. Enhanced depth imaging optical coherence tomography and indocyanine green angiography allow a better analysis of the subretinal pigment epithelium compartment. Conclusion: The differentiation between various kinds of PEDs is essential because each PED type is a distinct entity that has a specific pathogenesis, natural history, prognosis, and optimal treatment strategy. C1 [Mrejen, Sarah; Mukkamala, Krishna; Freund, K. Bailey] Vitreous Retina Macula Consultants New York, New York, NY 10022 USA. [Mrejen, Sarah; Mukkamala, Krishna; Freund, K. Bailey] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY 10021 USA. [Sarraf, David] Univ Calif Los Angeles, Jules Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA 90024 USA. [Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. RP Freund, KB (reprint author), Vitreous Retina Macula Consultants New York, 460 Pk Ave,Fifth Floor, New York, NY 10022 USA. EM kbfnyf@aol.com FU Macula Foundation, Inc. FX Supported in part by the Macula Foundation, Inc. NR 151 TC 24 Z9 26 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD OCT PY 2013 VL 33 IS 9 BP 1735 EP 1762 PG 28 WC Ophthalmology SC Ophthalmology GA 297DL UT WOS:000330235500002 PM 23873168 ER PT J AU Schneider, EW Elner, SG van Kuijk, FJ Goldberg, N Lieberman, RM Eliott, D Johnson, MW AF Schneider, Eric W. Elner, Susan G. van Kuijk, Frederik J. Goldberg, Naomi Lieberman, Ronni M. Eliott, Dean Johnson, Mark W. TI CHRONIC RETINAL NECROSIS Cytomegalovirus Necrotizing Retinitis Associated With Panretinal Vasculopathy in Non-HIV Patients SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE cytomegalovirus retinitis; acute retinal necrosis; progressive outer retinal necrosis; infectious retinitis; retinal vasculitis; posterior uveitis; neovascularization ID CELL-MEDIATED-IMMUNITY; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CHAIN-REACTION ANALYSIS; DIABETES-MELLITUS; STROMAL KERATITIS; VIRUS RETINITIS; AIDS; INFECTION; COUNTS; DIAGNOSIS AB Purpose: To characterize a unique cytomegalovirus (CMV)-associated retinopathy in patients with limited immune dysfunction. Methods: Retrospective observational case series. CMV was confirmed as the pathogenic agent via polymerase chain reaction analysis of aqueous or vitreous humor samples or via immunohistochemical analysis of retinal biopsy specimens. Results: Five non-HIV patients with granular necrotizing retinitis, vitritis, and severe occlusive vasculopathy were identified. Patient histories all suggested a basis for limited immune dysfunction including advanced age (n = 4), diabetes mellitus (n = 4), and noncytotoxic immunotherapy (n = 3). Diagnosis of CMV retinitis was delayed in all cases and patients received either no antiviral therapy (n = 2) or incorrect antiviral therapy (n = 3) for presumed herpes simplex/varicella zoster-related acute retinal necrosis. Retinitis subsequently regressed in all cases with introduction of systemic ganciclovir/valganciclovir (n = 5) and/or intravitreal foscarnet (n = 2). Four of five patients developed neovascularization because of extensive retinal ischemia. Conclusion: The clinical expression of CMV-associated retinopathy is strongly related to immune status. In patients with limited immune dysfunction, a mixed clinical picture of intraocular inflammation with panretinal occlusive vasculopathy, more characteristic of acute retinal necrosis, and peripheral slowly progressive granular retinitis, more characteristic of classic CMV retinitis, is observed. Recognition of this atypical clinical presentation, which the authors term chronic retinal necrosis, should prompt molecular testing for CMV to determine the appropriate antiviral therapy. Consideration should also be given to prophylactic panretinal photocoagulation in such eyes, given the high risk of neovascular complications. C1 [Schneider, Eric W.; Elner, Susan G.; Johnson, Mark W.] Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. [van Kuijk, Frederik J.] Univ Minnesota, Dept Ophthalmol, Minneapolis, MN 55455 USA. [Goldberg, Naomi; Lieberman, Ronni M.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA. [Eliott, Dean] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Johnson, MW (reprint author), Univ Michigan Hosp, WK Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, 1000 Wall St, Ann Arbor, MI 48105 USA. EM markwj@umich.edu FU Research to Prevent Blindness FX Supported by Research to Prevent Blindness Unrestricted Grant (E.V.K.). NR 35 TC 11 Z9 11 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD OCT PY 2013 VL 33 IS 9 BP 1791 EP 1799 PG 9 WC Ophthalmology SC Ophthalmology GA 297DL UT WOS:000330235500006 PM 23584702 ER PT J AU Rudolph, JW Foldy, EG Robinson, T Kendall, S Taylor, SS Simon, R AF Rudolph, Jenny W. Foldy, Erica Gabrielle Robinson, Traci Kendall, Sandy Taylor, Steven S. Simon, Robert TI Helping Without Harming The Instructor's Feedback Dilemma in Debriefing-A Case Study SO SIMULATION IN HEALTHCARE-JOURNAL OF THE SOCIETY FOR SIMULATION IN HEALTHCARE LA English DT Article DE Feedback; Debriefing; Faculty development; Debriefing the debriefer; Inter-professional education ID MEDICAL-EDUCATION; PATIENT SAFETY; PERFORMANCE; FAULTLINES; CONFLICT; BEHAVIOR; IMPACT; THREAT; TEAMS; WORK AB Introduction: Simulation instructors often feel caught in a task-versus-relationship dilemma. They must offer clear feedback on learners' task performance without damaging their relationship with those learners, especially in formative simulation settings. Mastering the skills to resolve this dilemma is crucial for simulation faculty development. Methods: We conducted a case study of a debriefer stuck in this task-versus-relationship dilemma. Data: The "2-column case" captures debriefing dialogue and instructor's thoughts and feelings or the "subjective experience." Analysis: The "learning pathways grid" guides a peer group of faculty in a step-by-step, retrospective analysis of the debriefing. The method uses vivid language to highlight the debriefer's dilemmas and how to surmount them. Results: The instructor's initial approach to managing the task-versus-relationship dilemma included (1) assuming that honest critiques will damage learners, (2) using vague descriptions of learner actions paired with guess-what-I-am-thinking questions, and (3) creating a context she worried would leave learners feeling neither safe nor clear how they could improve. This case study analysis identified things the instructor could do to be more effective including (1) making generous inferences about the learners' qualities, (2) normalizing the challenges posed by the simulation, (3) assuming there are different understandings of what it means to be a team. Conclusions: There are key assumptions and ways of interacting that help instructors resolve the task-versus-relationship dilemma. The instructor can then provide honest feedback in a rigorous yet empathic way to help sustain good or improve suboptimal performance in the future. C1 [Rudolph, Jenny W.; Simon, Robert] Ctr Med Simulat, Boston, MA USA. [Rudolph, Jenny W.; Simon, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rudolph, Jenny W.; Simon, Robert] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Foldy, Erica Gabrielle] NYU, Wagner Sch Publ Serv, New York, NY 10003 USA. [Robinson, Traci] Alberta Childrens Prov Gen Hosp, Calgary, AB, Canada. [Kendall, Sandy] Wellesley Coll, Wellesley, MA 02181 USA. [Taylor, Steven S.] Worcester Polytech Inst, Sch Business, Worcester, MA USA. RP Rudolph, JW (reprint author), 100 1st Ave,Suite 400, Boston, MA 02129 USA. EM JWRudolph@partners.org NR 97 TC 16 Z9 16 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-2332 EI 1559-713X J9 SIMUL HEALTHC JI Simul. Healthc. PD OCT PY 2013 VL 8 IS 5 BP 304 EP 316 DI 10.1097/SIH.0b013e318294854e PG 13 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 298EY UT WOS:000330308100003 PM 24084647 ER PT J AU Weinberg, I Jaff, MR AF Weinberg, Ido Jaff, Michael R. TI Inferior Vena Cava Filters Truth or Dare? SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material DE Editorials; deep vein thrombosis; inferior vena cava filter; pulmonary embolism; retrieval ID DEEP-VEIN THROMBOSIS; VENOUS THROMBOEMBOLISM; PULMONARY-EMBOLISM; MANAGEMENT; COMPLICATIONS; REMOVAL; RISK C1 [Weinberg, Ido; Jaff, Michael R.] Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA. RP Weinberg, I (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GB 852, Boston, MA 02114 USA. EM iweinberg@partners.org NR 18 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7640 EI 1941-7632 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD OCT PY 2013 VL 6 IS 5 BP 498 EP 500 DI 10.1161/CIRCINTERVENTIONS.113.000818 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 292SQ UT WOS:000329923100006 PM 24129933 ER PT J AU Armand, P Oki, Y Neuberg, DS Faham, M Cummings, C Klinger, M Weng, L Bhattar, S LaCasce, AS Jacobsen, ED Davids, MS Jacobson, C Fisher, DC Brown, JR Fowler, NH Rodriguez, MA Wallace, MJ Neelapu, SS Rodig, S Younes, A Freedman, AS AF Armand, Philippe Oki, Yasuhiro Neuberg, Donna S. Faham, Malek Cummings, Craig Klinger, Mark Weng, Li Bhattar, Sangeetha LaCasce, Ann S. Jacobsen, Eric D. Davids, Matthew S. Jacobson, Caron Fisher, David C. Brown, Jennifer R. Fowler, Nathan H. Rodriguez, M. Alma Wallace, Michael J. Neelapu, Sattva S. Rodig, Scott Younes, Anas Freedman, Arnold S. TI Detection of circulating tumour DNA in patients with aggressive B-cell non-Hodgkin lymphoma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE minimal residual disease; sequences; lymphomas ID RESIDUAL DISEASE DETECTION C1 [Armand, Philippe; Bhattar, Sangeetha; LaCasce, Ann S.; Jacobsen, Eric D.; Davids, Matthew S.; Jacobson, Caron; Fisher, David C.; Brown, Jennifer R.; Freedman, Arnold S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Oki, Yasuhiro; Fowler, Nathan H.; Rodriguez, M. Alma; Neelapu, Sattva S.; Younes, Anas] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA. [Neuberg, Donna S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Faham, Malek; Cummings, Craig; Klinger, Mark; Weng, Li] Sequenta Inc, San Francisco, CA USA. [Wallace, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA. [Rodig, Scott] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Armand, P (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM parmand@partners.org NR 8 TC 16 Z9 17 U1 3 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2013 VL 163 IS 1 BP 123 EP 126 DI 10.1111/bjh.12439 PG 4 WC Hematology SC Hematology GA 216YQ UT WOS:000324323300016 PM 23795711 ER PT J AU Pezzolesi, MG Krolewski, AS AF Pezzolesi, Marcus G. Krolewski, Andrzej S. TI Diabetic Nephropathy: Is ESRD Its Only Heritable Phenotype? SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID RENAL-FUNCTION DECLINE; RISK; MICROALBUMINURIA; GENES C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM Andrzej.Krolewski@joslin.harvard.edu NR 13 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 2013 VL 24 IS 10 BP 1505 EP 1507 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 277JN UT WOS:000328815000002 PM 24029425 ER PT J AU Sandholm, N McKnight, AJ Salem, RM Brennan, EP Forsblom, C Harjutsalo, V Makinen, VP McKay, GJ Sadlier, DM Williams, WW Martin, F Panduru, NM Tarnow, L Tuomilehto, J Tryggvason, K Zerbini, G Comeau, ME Langefeld, CD Godson, C Hirschhorn, JN Maxwell, AP Florez, JC Groop, PH AF Sandholm, Niina McKnight, Amy Jayne Salem, Rany M. Brennan, Eoin P. Forsblom, Carol Harjutsalo, Valma Makinen, Ville-Petteri McKay, Gareth J. Sadlier, Denise M. Williams, Winfred W. Martin, Finian Panduru, Nicolae Mircea Tarnow, Lise Tuomilehto, Jaakko Tryggvason, Karl Zerbini, Gianpaolo Comeau, Mary E. Langefeld, Carl D. Godson, Catherine Hirschhorn, Joel N. Maxwell, Alexander P. Florez, Jose C. Groop, Per-Henrik CA FIND Consortium FinnDiane Study Grp GENIE Consortium TI Chromosome 2q31.1 Associates with ESRD in Women with Type 1 Diabetes SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; GENE-EXPRESSION; SLIT DIAPHRAGM; CANCER-CELLS; NEPHROPATHY; KIDNEY; COMPLICATIONS; INHIBITION; PROTEINS; PROMOTER C1 [Sandholm, Niina; Forsblom, Carol; Harjutsalo, Valma; Makinen, Ville-Petteri; Groop, Per-Henrik] Folkhalsan Res Ctr, Folkhalsan Inst Genet, Helsinki, Finland. [Sandholm, Niina; Forsblom, Carol; Harjutsalo, Valma; Makinen, Ville-Petteri; Groop, Per-Henrik] Univ Helsinki, Cent Hosp, Dept Med, Div Nephrol, FIN-00014 Helsinki, Finland. [Sandholm, Niina] Aalto Univ, Dept Biomed Engn & Computat Sci, Espoo, Finland. [McKnight, Amy Jayne; McKay, Gareth J.; Maxwell, Alexander P.] Queens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland. [Salem, Rany M.; Hirschhorn, Joel N.; Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Salem, Rany M.; Hirschhorn, Joel N.] Childrens Hosp, Dept Endocrinol, Endocrine Res Unit, Boston, MA 02115 USA. [Salem, Rany M.; Williams, Winfred W.; Hirschhorn, Joel N.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Brennan, Eoin P.; Sadlier, Denise M.; Martin, Finian; Godson, Catherine] Univ Coll Dublin, Sch Med & Med Sci, Conway Inst, Diabet Res Ctr, Dublin 2, Ireland. [Brennan, Eoin P.; Sadlier, Denise M.; Martin, Finian; Godson, Catherine] Mater Misericordiae Univ Hosp, Dublin 7, Ireland. [Harjutsalo, Valma; Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland. [Makinen, Ville-Petteri] Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA USA. [Williams, Winfred W.; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Panduru, Nicolae Mircea] Carol Davila Univ Med & Pharm, Clin Dept 2, Bucharest, Romania. [Tarnow, Lise] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark. [Tarnow, Lise] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Tuomilehto, Jaakko] South Ostrobothnia Cent Hosp, Seinajoki, Finland. [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria. [Tuomilehto, Jaakko] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia. [Tryggvason, Karl] Karolinska Inst, Dept Med Biochem & Biophys, Div Matrix Biol, Stockholm, Sweden. [Zerbini, Gianpaolo] Ist Sci San Raffaele, Div Metab & Cardiovasc Sci, Complicat Diabet Unit, I-20132 Milan, Italy. [Comeau, Mary E.; Langefeld, Carl D.] Wake Forest Sch Med, Ctr Publ Hlth Genom, Dept Biostat, Winston Salem, NC USA. [Maxwell, Alexander P.] Belfast City Hosp, Reg Nephrol Unit, Belfast BT9 7AD, Antrim, North Ireland. [Groop, Per-Henrik] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia. RP Groop, PH (reprint author), Univ Helsinki, Cent Hosp, Biomedicum Helsinki, Div Nephrol,Dept Med, Haartmaninkatu 8,POB 63, FIN-00014 Helsinki, Finland. EM per-henrik.groop@helsinki.fi OI McKnight, Amy Jayne/0000-0002-7482-709X; Makinen, Ville-Petteri/0000-0002-7262-2656; Maxwell, Alexander P./0000-0002-6110-7253 FU Eli Lilly; Roche FX J.C.F. has received consulting honoraria from Novartis, Lilly, and Pfizer. P.H.G. has received lecture honoraria from Abbott, Boehringer Ingelheim, Cebix, Eli Lilly, Genzyme, Novartis, Novo Nordisk, and MSD and research grants from Eli Lilly and Roche. P.H.G. is also an advisory board member of Boehringer Ingelheim and Novartis. NR 28 TC 20 Z9 21 U1 1 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 2013 VL 24 IS 10 BP 1537 EP 1543 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 277JN UT WOS:000328815000008 PM 24029427 ER PT J AU Wen, LS Kosowsky, JM Gurrola, ER Camargo, CA AF Wen, Leana S. Kosowsky, Joshua M. Gurrola, Edith R. Camargo, Carlos A., Jr. TI The provision of diagnosis at emergency department discharge: a pilot study SO EMERGENCY MEDICINE JOURNAL LA English DT Article ID UNSCHEDULED RETURNS; URBAN AB Objectives Understanding the cause of patients' symptoms usually involves identification of a pathological diagnosis. Anecdotal reports suggest that emergency department (ED) providers do not prioritise giving pathological diagnoses, and often reiterate the patient's symptom as the discharge 'diagnosis'. Our pilot study sought to identify the proportion of patients at a large teaching hospital who receive a symptomatic versus pathological diagnosis at ED discharge. Methods We performed a chart review of all adult patients who were discharged from an urban ED in the USA, with an 88 000 annual visit volume. All charts of patients presenting with the three most common ED chief complaints (chest pain, abdominal pain and headache) were reviewed by two reviewers. Charts were coded as either symptomatic or pathological diagnosis based on the discharge diagnosis provided by the attending physician. Those with discrepant coding by the two reviewers were subject to review by a third adjudicator. Results 797 charts met the inclusion criteria. Five charts (0.6%) were coded differently by the two reviewers; a discussion with the third reviewer resulted in consensus in all cases. For patients presenting with chest pain, abdominal pain and headache, the proportion that received a pathological ED discharge diagnosis were 17%, 43% and 41%, respectively. Conclusions According to our pilot study, most patients are discharged from the ED without a pathological diagnosis that explains the likely cause of their symptoms. Future studies will investigate whether this finding is consistent across institutions, and whether provision of a pathological diagnosis affects clinical outcomes and patient satisfaction. C1 [Wen, Leana S.] Brigham & Womens Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. [Kosowsky, Joshua M.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Gurrola, Edith R.] Univ Arizona, Dept Emergency Med, Phoenix, AZ USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Wen, LS (reprint author), Brigham & Womens Hosp, Massachusetts Gen Hosp, Dept Emergency Med, Neville House,75 Francis St, Boston, MA 02115 USA. EM wen.leana@gmail.com OI Wen, Leana/0000-0003-0259-0537 FU Massachusetts American College of Emergency Physicians; Department of Emergency Medicine at Brigham & Women's Hospital FX This project is being funded by grants from the Massachusetts American College of Emergency Physicians and Department of Emergency Medicine at Brigham & Women's Hospital. NR 10 TC 1 Z9 1 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1472-0205 EI 1472-0213 J9 EMERG MED J JI Emerg. Med. J. PD OCT PY 2013 VL 30 IS 10 BP 801 EP 803 DI 10.1136/emermed-2012-201749 PG 3 WC Emergency Medicine SC Emergency Medicine GA 267XI UT WOS:000328131300007 PM 23100316 ER PT J AU Juillerat, P Wasan, SK Fowler, SA Friedman, S Pabby, VK Coukas, JA Barto, AE Pellish, R Germansky, KA Cheifetz, AS Korzenik, JR Farraye, FA Yajnik, V AF Juillerat, Pascal Wasan, Sharmeel K. Fowler, Sharyle A. Friedman, Sonia Pabby, Vikas K. Coukas, Jennifer A. Barto, Amy E. Pellish, Randall Germansky, Katharine A. Cheifetz, Adam S. Korzenik, Joshua R. Farraye, Francis A. Yajnik, Vijay TI Efficacy and Safety of Natalizumab in Crohn's Disease Patients Treated at 6 Boston Academic Hospitals SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE Crohn's disease; inflammatory bowel disease; natalizumab; safety; efficacy; clinical practice ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; REMISSION; ANTIBODY; THERAPY; TRIAL; INDEX; RISK AB Background:Despite trials demonstrating its efficacy, many physicians harbor concerns regarding the use of natalizumab in the treatment of patients with refractory Crohn's disease (CD). The purpose of this study was to perform a descriptive analysis of a series of CD patients not currently enrolled in a clinical trial. Methods: A retrospective case review of patients treated with natalizumab at 6 sites in Massachusetts: Boston Medical Center, Beth Israel Deaconess Medical Center, Brigham & Women's Hospital, Lahey Clinic, Massachusetts General Hospital, and UMass Medical Center. Results: Data on 69 CD patients on natalizumab were collected. At the start of treatment, patients' disease duration was 12 years. A high proportion of patients were women (68%), presented with perianal disease (65%) and upper gastrointestinal tract involvement (14%). Prior nonbiologic therapies were steroids (96%), thiopurines (94%), antibiotics (74%), methotrexate (58%), and at least two anti-tumor necrosis factor agent failures (81%). Sixty-nine percent (44 of 64 patients) with available medical evaluation had a partial or complete clinical response. Loss of response was 13% after an average of 1 year of treatment. Adverse events were infusion reactions, headaches, fever, and infections. No case of progressive multifocal leukoencephalopathy was observed. Conclusions: In our clinical experience outside the context of a clinical trial, natalizumab is largely reserved for CD patients with extensive ileocolonic disease who have failed conventional immunosuppressants and of at least 2 anti-tumor necrosis factor agents. This drug is, however, well tolerated and offers significant clinical improvement for more than a year in one-third of these difficult-to-treat CD patients. C1 [Juillerat, Pascal; Fowler, Sharyle A.; Korzenik, Joshua R.; Yajnik, Vijay] Massachusetts Gen Hosp, Dept Gastroenterol & Hepatol, MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. [Juillerat, Pascal; Fowler, Sharyle A.; Korzenik, Joshua R.; Yajnik, Vijay] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Juillerat, Pascal] Univ Bern, Inselspital, Univ Hosp Bern, Div Gastroenterol,Clin Visceral Surg & Med, CH-3010 Bern, Switzerland. [Wasan, Sharmeel K.; Coukas, Jennifer A.; Farraye, Francis A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Friedman, Sonia; Pabby, Vikas K.; Korzenik, Joshua R.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Barto, Amy E.] Lahey Clin Fdn, Burlington, MA USA. [Pellish, Randall] Univ Massachusetts, Worcester, MA 01605 USA. [Germansky, Katharine A.; Cheifetz, Adam S.] Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. RP Juillerat, P (reprint author), Massachusetts Gen Hosp, Dept Gastroenterol & Hepatol, MGH Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM pascal_juillerat@post.harvard.edu FU Swiss National Science Foundation (SNF) [PBLAP3-124341] FX Supported by the Swiss National Science Foundation (SNF) Grant PBLAP3-124341. NR 19 TC 12 Z9 12 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD OCT PY 2013 VL 19 IS 11 BP 2457 EP 2463 DI 10.1097/MIB.0b013e3182a32a0d PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 284XE UT WOS:000329354500024 PM 23962896 ER PT J AU Sevc, J Goldberg, D van Gorp, S Leerink, M Juhas, S Juhasova, J Marsala, S Hruska-Plochan, M Hefferan, MP Motlik, J Rypacek, F Machova, L Kakinohana, O Santucci, C Johe, K Lukacova, N Yamada, K Bui, JD Marsala, M AF Sevc, Juraj Goldberg, Danielle van Gorp, Sebastiaan Leerink, Marjolein Juhas, Stefan Juhasova, Jana Marsala, Silvia Hruska-Plochan, Marian Hefferan, Michael P. Motlik, Jan Rypacek, Frantisek Machova, Ludka Kakinohana, Osamu Santucci, Camila Johe, Karl Lukacova, Nadezda Yamada, Kazuhiko Bui, Jack D. Marsala, Martin TI Effective long-term immunosuppression in rats by subcutaneously implanted sustained-release tacrolimus pellet: Effect on spinally grafted human neural precursor survival SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Immunosuppression; Xenograft; Human neural precursors; Spinal grafting; Sprague-Dawley rat; T-lymphocyte; Tacrolimus pellet ID STEM-CELLS; MYCOPHENOLATE-MOFETIL; ORGAN-TRANSPLANTATION; PARKINSONS-DISEASE; FK506; MODEL; PHARMACOKINETICS; PHARMACODYNAMICS; NEPHROTOXICITY; DIFFERENTIATION AB Achievement of effective, safe and long-term immunosuppression represents one of the challenges in experimental allogeneic and xenogeneic cell and organ transplantation. The goal of the present study was to develop a reliable, long-term immunosuppression protocol in Sprague-Dawley (SD) rats by: 1) comparing the pharmacokinetics of four different subcutaneously delivered/implanted tacrolimus (TAC) formulations, including: i) caster oil/saline solution, ii) unilamellar or multilamellar liposomes, iii) biodegradable microspheres, and iv) biodegradable 3-month lasting pellets; and 2) defining the survival and immune response in animals receiving spinal injections of human neural precursors at 6 weeks to 3 months after cell grafting. In animals implanted with TAC pellets (3.4 mg/kg/day), a stable 3-month lasting plasma concentration of TAC averaging 19.1 +/- 4.9 ng/ml was measured. Analysis of grafted cell survival in SOD + or spinal trauma-injured SD rats immunosuppressed with 3-month lasting TAC pellets (3.4-5.1 mg/kg/day) showed the consistent presence of implanted human neurons with minimal or no local T-cell infiltration. These data demonstrate that the use of TAC pellets can represent an effective, long-lasting immunosuppressive drug delivery system that is safe, simple to implement and is associated with a long-term human neural precursor survival after grafting into the spinal cord of SOD+ or spinal trauma-injured SD rats. Published by Elsevier Inc. C1 [Sevc, Juraj; Goldberg, Danielle; Leerink, Marjolein; Marsala, Silvia; Hruska-Plochan, Marian; Kakinohana, Osamu; Santucci, Camila; Marsala, Martin] UCSD, Dept Anesthesiol, Neuroregenerat Lab, La Jolla, CA 92037 USA. [Sevc, Juraj] Safarik Univ, Fac Sci, Inst Biol & Ecol, Kosice 04001, Slovakia. [van Gorp, Sebastiaan] Maastricht Univ, Med Ctr, Dept Anesthesiol, NL-6202 AZ Maastricht, Netherlands. [Juhas, Stefan; Juhasova, Jana; Hruska-Plochan, Marian; Motlik, Jan] Acad Sci Czech Republic, Inst Anim Physiol & Genet, Libechov 27721, Czech Republic. [Hruska-Plochan, Marian] Charles Univ Prague, Fac Sci, Dept Cell Biol, Prague, Czech Republic. [Rypacek, Frantisek; Machova, Ludka] Acad Sci Czech Republic, Inst Macromol Chem, Prague 16206 6, Czech Republic. [Hefferan, Michael P.; Johe, Karl] Neuralstem Inc, Rockville, MD 20850 USA. [Lukacova, Nadezda] Slovak Acad Sci, Inst Neurobiol, Kosice 04001, Slovakia. [Yamada, Kazuhiko] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Bui, Jack D.] UCSD, Dept Pathol, La Jolla, CA 92037 USA. RP Marsala, M (reprint author), UCSD, Sanford Consortium Regenerat Med, Dept Anesthesiol, Neuroregenerat Lab, 2880 Torrey Pines Scen Dr, La Jolla, CA 92037 USA. EM mmarsala@ucsd.edu RI Juhasova, Jana/G-7144-2014; Rypacek, Frantisek/G-7872-2014; Motlik, Jan/G-7148-2014; Juhas, Stefan/G-7141-2014; Hruska-Plochan, Marian/I-3982-2014 OI Juhasova, Jana/0000-0001-7022-6812; Juhas, Stefan/0000-0002-2866-0727; FU CIRM; Neuralstem Inc.; ITMS [26220220127]; [TA01011466]; [CZ.1.05./2.1.00/03.0124]; [RVO: 67985904]; [APVV-0314-06] FX This study was funded by CIRM and by Neuralstem Inc. (M.M.), TA01011466, CZ.1.05./2.1.00/03.0124 and RVO: 67985904 (S.J., J.J., J.M.), ITMS 26220220127 (Research & Development Operational Programme, ERDF) and APVV-0314-06 (N.L). No relationship with Astellas Pharma exists for any of the authors. NR 41 TC 9 Z9 9 U1 1 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 2013 VL 248 BP 85 EP 99 DI 10.1016/j.expneurol.2013.05.017 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 261SJ UT WOS:000327684600009 PM 23748136 ER PT J AU Leonardis, RL Duvvuri, U Mehta, D AF Leonardis, Rachel L. Duvvuri, Umamaheswar Mehta, Deepak TI Transoral Robotic-Assisted Lingual Tonsillectomy in the Pediatric Population SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID OBSTRUCTIVE SLEEP-APNEA; SURGERY; HEAD; NECK; OTOLARYNGOLOGY; SAFETY AB IMPORTANCE Since technologic advances allow the use of robotic assistance in various surgical interventions performed to treat pediatric otolaryngology patients, the feasibility and outcomes of potential procedures must be assessed. OBJECTIVE To assess the feasibility and outcomes of robotic-assisted lingual tonsillectomy in the pediatric population. DESIGN, SETTING, AND PARTICIPANTS Retrospective medical record review in a tertiary care children's hospital of 16 pediatric patients who underwent robotic-assisted lingual tonsillectomy from March 1, 2011, through December 31, 2012. INTERVENTION All patients underwent robotic-assisted lingual tonsillectomy using the da Vinci Surgical System (Intuitive Surgical, Inc) at the Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center. MAIN OUTCOMES AND MEASURES Demographic data, comorbidities, robot docking time, operative time, estimated blood loss, and postoperative course, including complications in the immediate and longer-term postoperative period, were collected and analyzed. RESULTS All patients successfully underwent lingual tonsillectomy using the da Vinci Surgical System. Endotracheal intubation was performed in all patients and did not interfere with visualization of the oropharynx. Optimal retraction allowed visualization of pertinent structures and maximized transoral access. A significant learning curve from the first 5 surgical cases to subsequent cases with respect to robot docking time was observed (9 vs 3 minutes, respectively; P < .05). Operative time, estimated blood loss, and postoperative complication profiles are within the expected and acceptable limitations for performing lingual tonsillectomy in the pediatric population. CONCLUSIONS AND RELEVANCE Technologic advances have allowed miniaturization of robotic instrumentation and have expanded the scope of surgical options for the pediatric airway. Robotic-assisted lingual tonsillectomy is well tolerated and can be performed in the pediatric population with excellent success. It should be considered a feasible option for implementation at an institution-based level. C1 [Leonardis, Rachel L.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Duvvuri, Umamaheswar] Univ Pittsburgh, Vet Affairs Pittsburgh Hlth Syst, Med Ctr, Inst Eye & Ear,Dept Otolaryngol, Pittsburgh, PA 15213 USA. [Mehta, Deepak] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Dept Otolaryngol, Pittsburgh, PA 15213 USA. RP Duvvuri, U (reprint author), Univ Pittsburgh, Vet Affairs Pittsburgh Hlth Syst, Med Ctr, Inst Eye & Ear,Dept Otolaryngol, 203 Lothrop St,Ste 300, Pittsburgh, PA 15213 USA. EM duvvuriu@upmc.edu NR 15 TC 8 Z9 8 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6181 EI 2168-619X J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD OCT PY 2013 VL 139 IS 10 BP 1032 EP 1036 DI 10.1001/jamaoto.2013.4924 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 279DU UT WOS:000328941400007 PM 24135744 ER PT J AU Putman, MS Yu, EW Lee, H Neer, RM Schindler, E Taylor, AP Cheston, E Bouxsein, ML Finkelstein, JS AF Putman, Melissa S. Yu, Elaine W. Lee, Hang Neer, Robert M. Schindler, Elizabeth Taylor, Alexander P. Cheston, Emily Bouxsein, Mary L. Finkelstein, Joel S. TI Differences in Skeletal Microarchitecture and Strength in African-American and White Women SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE HR-PQCT; BONE MICROARCHITECTURE; MICRO-FINITE ELEMENT ANALYSIS; AFRICAN-AMERICAN; WHITE ID QUANTITATIVE COMPUTED-TOMOGRAPHY; BONE-MINERAL DENSITY; FINITE-ELEMENT-ANALYSIS; VIVO HR-PQCT; DISTAL RADIUS; CORTICAL BONE; PROXIMAL FEMUR; FRACTURE RISK; POSTMENOPAUSAL WOMEN; ETHNIC VARIATION AB African-American women have a lower risk of fracture than white women, and this difference is only partially explained by differences in dual-energy X-ray absorptiometry (DXA) areal bone mineral density (aBMD). Little is known about racial differences in skeletal microarchitecture and the consequences for bone strength. To evaluate potential factors underlying this racial difference in fracture rates, we used high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess cortical and trabecular bone microarchitecture and estimate bone strength using micro-finite element analysis (mu FEA) in African-American (n=100) and white (n=173) women participating in the Study of Women's Health Across the Nation (SWAN). African-American women had larger and denser bones than whites, with greater total area, aBMD, and total volumetric BMD (vBMD) at the radius and tibia metaphysis (p<0.05 for all). African-Americans had greater trabecular vBMD at the radius, but higher cortical vBMD at the tibia. Cortical microarchitecture tended to show the most pronounced racial differences, with higher cortical area, thickness, and volumes in African-Americans at both skeletal sites (p<0.05 for all), and lower cortical porosity in African-Americans at the tibia (p<0.05). African-American women also had greater estimated bone stiffness and failure load at both the radius and tibia. Differences in skeletal microarchitecture and estimated stiffness and failure load persisted even after adjustment for DXA aBMD. The densitometric and microarchitectural predictors of failure load at the radius and tibia were the same in African-American and white women. In conclusion, differences in bone microarchitecture and density contribute to greater estimated bone strength in African-Americans and probably explain, at least in part, the lower fracture risk of African-American women. (c) 2013 American Society for Bone and Mineral Research. C1 [Putman, Melissa S.; Yu, Elaine W.; Neer, Robert M.; Schindler, Elizabeth; Taylor, Alexander P.; Cheston, Emily; Bouxsein, Mary L.; Finkelstein, Joel S.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Putman, Melissa S.; Yu, Elaine W.; Neer, Robert M.; Schindler, Elizabeth; Taylor, Alexander P.; Cheston, Emily; Bouxsein, Mary L.; Finkelstein, Joel S.] Harvard Univ, Sch Med, Boston, MA USA. [Putman, Melissa S.] Boston Childrens Hosp, Div Endocrine, Boston, MA USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Putman, MS (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,THR 1051, Boston, MA 02114 USA. EM msputman@partners.org FU National Institutes of Health (NIH); DHHS through the National Institute on Aging (NIA); National Institute of Nursing Research (NINR); NIH Office of Research on Women's Health (ORWH) [NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495]; NCRR Shared Equipment Grant [1S10RR023405-01] FX The Study of Women's Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR) and the NIH Office of Research on Women's Health (ORWH) (NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495). The HR-pQCT measurements were made possible by an NCRR Shared Equipment Grant (1S10RR023405-01). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIA, NINR, ORWH, or the NIH. NR 39 TC 18 Z9 18 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2013 VL 28 IS 10 BP 2177 EP 2185 DI 10.1002/jbmr.1953 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 282EM UT WOS:000329153100013 PM 23572415 ER PT J AU Catassi, C Bai, JC Bonaz, B Bouma, G Calabro, A Carroccio, A Castillejo, G Ciacci, C Cristofori, F Dolinsek, J Francavilla, R Elli, L Green, P Holtmeier, W Koehler, P Koletzko, S Meinhold, C Sanders, D Schumann, M Schuppan, D Ullrich, R Vecsei, A Volta, U Zevallos, V Sapone, A Fasano, A AF Catassi, Carlo Bai, Julio C. Bonaz, Bruno Bouma, Gerd Calabro, Antonio Carroccio, Antonio Castillejo, Gemma Ciacci, Carolina Cristofori, Fernanda Dolinsek, Jernej Francavilla, Ruggiero Elli, Luca Green, Peter Holtmeier, Wolfgang Koehler, Peter Koletzko, Sibylle Meinhold, Christof Sanders, David Schumann, Michael Schuppan, Detlef Ullrich, Reiner Vecsei, Andreas Volta, Umberto Zevallos, Victor Sapone, Anna Fasano, Alessio TI Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders SO NUTRIENTS LA English DT Review DE gluten sensitivity; celiac disease; wheat allergy; gluten-related disorders; gluten-free diet ID AUTISM SPECTRUM DISORDERS; CONTROLLED-TRIAL; FREE DIET; DISEASE; CHILDREN; BLIND; WHEAT; PREVALENCE; CHALLENGE; SYMPTOMS AB Non Celiac Gluten sensitivity (NCGS) was originally described in the 1980s and recently a re-discovered disorder characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected with either celiac disease (CD) or wheat allergy (WA). Although NCGS frequency is still unclear, epidemiological data have been generated that can help establishing the magnitude of the problem. Clinical studies further defined the identity of NCGS and its implications in human disease. An overlap between the irritable bowel syndrome (IBS) and NCGS has been detected, requiring even more stringent diagnostic criteria. Several studies suggested a relationship between NCGS and neuropsychiatric disorders, particularly autism and schizophrenia. The first case reports of NCGS in children have been described. Lack of biomarkers is still a major limitation of clinical studies, making it difficult to differentiate NCGS from other gluten related disorders. Recent studies raised the possibility that, beside gluten, wheat amylase-trypsin inhibitors and low-fermentable, poorly-absorbed, short-chain carbohydrates can contribute to symptoms (at least those related to IBS) experienced by NCGS patients. In this paper we report the major advances and current trends on NCGS. C1 [Catassi, Carlo] Univ Politecn Marche, Dept Pediat, I-60121 Ancona, Italy. [Bai, Julio C.] Hosp Gastroenterol Dr Carlos Bonorino Udaondo, Dept Med, RA-1264 Buenos Aires, DF, Argentina. [Bonaz, Bruno] CHU Grenoble, Dept Gastroenterol & Liver Dis, F-38043 Grenoble, France. [Bouma, Gerd] Vrije Univ Med Ctr, Dept Gastroenterol & Hepatol, NL-1081 HV Amsterdam, Netherlands. [Calabro, Antonio] Univ Florence, Dept Expt & Clin Biomed Sci, Gastroenterol Unit, I-50134 Florence, Italy. [Carroccio, Antonio] Giovanni Paolo II Hosp, Dept Internal Med, Sciacca, AG, Italy. [Carroccio, Antonio] Univ Palermo, I-92019 Sciacca, Italy. [Castillejo, Gemma] Univ Rovira & Virgili, Hosp Univ St Joan de Reus, Pediat Gastroenterol Unit, Tarragona 43204, Spain. [Ciacci, Carolina] Univ Salerno, Dept Med & Surg, I-84081 Salerno, Italy. [Cristofori, Fernanda; Francavilla, Ruggiero] Univ Bari, Interdisciplinary Dept Med, I-70124 Bari, Italy. [Dolinsek, Jernej] Univ Med Ctr Maribor, Dept Pediat, Gastroenterol Unit, Maribor 2000, Slovenia. [Elli, Luca] Ctr Prevenz & Diagnosi Malattia Celiaca Fdn IRCCS, I-20122 Milan, Italy. [Green, Peter] Columbia Univ Med Ctr, Dept Med, Celiac Dis Ctr, New York, NY 10032 USA. [Holtmeier, Wolfgang] Hosp Porz Rhein, Div Gastroenterol & Internal Med, D-51149 Cologne, Germany. [Koehler, Peter] Leibniz Inst, German Res Ctr Food Chem, D-85354 Freising Weihenstephan, Germany. [Koletzko, Sibylle] Univ Munich Med Ctr, Dr von Hauner Childrens Hosp, Div Pediat Gastroenterol & Hepatol, D-80337 Munich, Germany. [Meinhold, Christof] Practice Nutr Therapy Meinhold & Team, D-50674 Cologne, Germany. [Sanders, David] Royal Hallamshire Hosp, Dept Gastroenterol & Hepatol, Sheffield S10 2JF, S Yorkshire, England. [Sanders, David] Univ Sheffield Med Sch, Sheffield S10 2JF, S Yorkshire, England. [Schumann, Michael; Ullrich, Reiner] Charite, Dept Gastroenterol Rheumatol & Infectiol, D-10203 Berlin, Germany. [Schuppan, Detlef; Zevallos, Victor] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Med 1, D-55131 Mainz, Germany. [Schuppan, Detlef] Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. [Schuppan, Detlef] Beth Israel Deaconess Med Ctr, Celiac Ctr, Boston, MA 02215 USA. [Schuppan, Detlef] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Vecsei, Andreas] St Anna Childrens Hosp, A-1090 Vienna, Austria. [Volta, Umberto] Univ Bologna, Dept Med & Surg Sci, I-40138 Bologna, Italy. [Sapone, Anna] Univ Naples 2, Dept Gastroenterol, I-80136 Naples, Italy. [Fasano, Alessio] MassGen Hosp Children, Boston, MA 02129 USA. RP Fasano, A (reprint author), MassGen Hosp Children, Boston, MA 02129 USA. EM catassi@tin.it; jbai@intramed.net; bbonaz@chu-grenoble.fr; g.bouma@vumc.nl; a.calabro@dfc.unifi.it; acarroccio@hotmail.com; gcv@tinet.cat; cciacci@unisa.it; fernandacristofori@gmail.com; jernej.dolinsek@ukc-mb.si; rfrancavilla@gmail.com; lucelli@yahoo.com; pg11@columbia.edu; w.holtmeier@khporz.de; peter.koehler@tum.de; sybille.koletzko@med.uni-muenchen.de; praxis@christof-meinhold.de; david.sanders@sth.nhs.uk; michael.schumann@charite.de; dschuppa@bidmc.harvard.edu; reiner.ullrich@charite.de; andreas.vecsei@stanna.at; uvolt@yahoo.com; zevallos@uni-mainz.de; annasapone@yahoo.it; afasano@partners.org RI ciacci, carolina/A-2594-2012; bouma, gerd/E-2520-2013; Carroccio, Antonio/K-4484-2016; Schumann, Michael/K-6426-2013; OI ciacci, carolina/0000-0002-7426-1145; Carroccio, Antonio/0000-0001-8913-7916; Schumann, Michael/0000-0001-6391-9979; Volta, Umberto/0000-0003-3405-3808; Francavilla, Ruggiero/0000-0002-4603-974X; Elli, Luca/0000-0002-0873-0759 FU Schar; Menarini Diagnostics FX Carlo Catassi received consulting fees from Schar and Menarini Diagnostics. Luca Elli and Anna Sapone received consulting fees from Schar. Peter Green is a member of the scientific advisory board of Alvine Pharmaceuticals and Alba Therapeutics. Alessio Fasano owns stock in Alba Therapeutics. The other authors declared no conflict of interest. NR 40 TC 153 Z9 157 U1 15 U2 150 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6643 J9 NUTRIENTS JI Nutrients PD OCT PY 2013 VL 5 IS 10 BP 3839 EP 3853 DI 10.3390/nu5103839 PG 15 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 274TA UT WOS:000328627900003 PM 24077239 ER PT J AU Azzam, PN Gopalan, PR AF Azzam, Pierre N. Gopalan, Priya R. TI A 44-Year-Old Man with Agitation after Stroke SO PSYCHIATRIC ANNALS LA English DT Editorial Material ID SUBARACHNOID HEMORRHAGE; BRAIN-INJURY; AMNESIA; IMPAIRMENT; LESIONS; MEMORY; VOLUME C1 [Azzam, Pierre N.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. [Azzam, Pierre N.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Gopalan, Priya R.] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA. RP Azzam, PN (reprint author), VA Med Ctr West, Roxbury Campus,GD 110,1400 VFW Pkwy, Boston, MA 02132 USA. EM pierre.azzam@va.gov NR 17 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 EI 1938-2456 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD OCT PY 2013 VL 43 IS 10 BP 470 EP 472 DI 10.3928/00485713-20131003-09 PG 3 WC Psychiatry SC Psychiatry GA 282SG UT WOS:000329192600009 ER PT J AU West, JS Price, M Gros, KS Ruggiero, KJ AF West, Jenny S. Price, Matthew Gros, Kirstin Stauffacher Ruggiero, Kenneth J. TI Community Support as a Moderator of Postdisaster Mental Health Symptoms in Urban and Nonurban Communities SO DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS LA English DT Article DE community support; urban nonurban; PTSD; depression ID SOCIAL SUPPORT; NATURAL DISASTER; HURRICANE IKE; PSYCHOLOGICAL DISTRESS; VIOLENT CRIME; STRESS; INTERVENTION; PTSD; ADULTS; CONSERVATION AB Objective We examined the association between disaster exposure, community support, and mental health outcomes in urban and nonurban participants of Galveston and Chambers counties after Hurricane Ike. The moderating effect of community support was evaluated as a protective factor relative to postdisaster mental health. Methods A representative population-based sample of 157 urban and 714 nonurban adults were interviewed 12 to 17 months after the hurricane about their mental health functioning, disaster exposure, and perceptions of community support. Results A series of multiple regressions demonstrated that disaster exposure was associated with mental health outcomes for both groups. The strength of the association varied across population samples.Community support moderated the association between interpersonal effects of the disaster and posttraumatic stress disorder (PTSD) and depression outcomes in nonurban participants and the association between property damage and PTSD in urban participants. Conclusions Community support played a larger role in reducing PTSD and depression symptoms associated with the interpersonal effects of a disaster in the nonurban sample only. Communities may play a more beneficial role in the recovery process in nonurban areas that have elevated levels of injury or death attributed to a disaster. C1 [West, Jenny S.; Price, Matthew; Gros, Kirstin Stauffacher; Ruggiero, Kenneth J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Price, Matthew; Gros, Kirstin Stauffacher; Ruggiero, Kenneth J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [West, Jenny S.] Univ Calif Irvine, Irvine, CA USA. RP Ruggiero, KJ (reprint author), Med Univ S Carolina, Natl Crime Victims Ctr, 67 President St, Charleston, SC 29425 USA. EM prima@musc.edu FU National Institutes of Mental Health [R34MH77149]; [T32MH018869] FX This study is supported by the National Institutes of Mental Health Grant R34MH77149 (Dr Ruggiero). Dr. Price is supported by T32MH018869. NR 34 TC 2 Z9 2 U1 2 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1935-7893 EI 1938-744X J9 DISASTER MED PUBLIC JI Dis. Med. Public Health Prep. PD OCT PY 2013 VL 7 IS 5 BP 443 EP 451 DI 10.1017/dmp.2013.74 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 273PC UT WOS:000328546700003 PM 24274123 ER PT J AU Yoo, JW Kim, S Seol, H Kim, SJ Yang, JM Ryu, WS Min, TJ Choi, JB Kwon, M Nakagawa, S AF Yoo, Ji Won Kim, Sulgi Seol, Haesun Kim, Sun Jung Yang, Janet Miyoung Ryu, Woo Sang Min, Too Jae Choi, Jong Bum Kwon, Minkyung Nakagawa, Shunichi TI Effects of an internal medicine floor interdisciplinary team on hospital and clinical outcomes of seniors with acute medical illness SO GERIATRICS & GERONTOLOGY INTERNATIONAL LA English DT Article DE clinical education; geriatric assessment; hospital medicine; interdisciplinary team; quality improvement ID CONFUSION ASSESSMENT METHOD; LENGTH-OF-STAY; PROSPECTIVE-PAYMENT; DELIRIUM; GERIATRICS; RELIABILITY; RESIDENTS; TRENDS; RISK; CARE AB AimTo examine whether an internal medicine interdisciplinary floor team enhances the hospital and clinical outcomes for seniors with acute medical illness. MethodsSeniors admitted to medical floor teaching services of a USA teaching hospital were recruited and allocated to the interdisciplinary (ITD; n=236) and usual care teams (n=248). Compared with the usual care team, the interdisciplinary team physicians carried out daily geriatric assessment and management, and led the interdisciplinary team meeting designed for improving interprofessional collaboration. ResultsAfter controlling for patient and physician characteristics, the mean hospital length of stay in the ITD team (6.1 days; 95% CI 5.2-7.7 days) was 0.7 days shorter than that in the usual care team (6.8 days; 95% CI 5.7-8.3 days; P=0.008). There was no significant difference in delirium and 30-day hospital readmission between care groups. ConclusionsNotwithstanding partly positive associations, the results from the present study suggest that interdisciplinary team-based care is, at best, associated with enhancing the clinical and hospital outcomes for seniors with acute medical illness. Geriatr Gerontol Int 2013; 13: 942-948. C1 [Yoo, Ji Won] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. [Yoo, Ji Won] Univ Michigan, Sch Med, Inst Gerontol, Ann Arbor, MI 48109 USA. [Yang, Janet Miyoung] St Joseph Mercy, Dept Internal Med, Ann Arbor, MI USA. [Kim, Sulgi] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Seol, Haesun] VNA Hlth Ctr, Federally Qualified Hlth Ctr, Bensenville, IL USA. [Nakagawa, Shunichi] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY USA. [Nakagawa, Shunichi] James J Peters Vet Affairs Med Ctr, GRECC, Bronx, NY USA. [Yoo, Ji Won] Korea Univ, Coll Med, Dept Internal Med, Seoul 136705, South Korea. [Ryu, Woo Sang; Min, Too Jae] Korea Univ, Coll Med, Ctr Clin Educ, Seoul 136705, South Korea. [Kim, Sun Jung] Yonsei Univ, Sch Publ Hlth, Seoul 120749, South Korea. [Choi, Jong Bum; Kwon, Minkyung] Yonsei Univ, Coll Med, Ctr Clin Educ, Seoul, South Korea. RP Yoo, JW (reprint author), Univ Michigan, Sch Med, Dept Internal Med, 300 North Ingalls Bldg,Room 932, Ann Arbor, MI 48109 USA. EM yoojiw@trinity-health.org RI Kwon, Minkyung/H-3787-2012 OI Kwon, Minkyung/0000-0003-2437-7606 FU Junior Researcher Seed Grant (American Geriatrics Society); Excellence for Graduate Medical Education Grant (Ministry of Education, Science and Technology, Republic of Korea) FX This study was funded by a Junior Researcher Seed Grant (American Geriatrics Society) and an Excellence for Graduate Medical Education Grant (Ministry of Education, Science and Technology, Republic of Korea). NR 31 TC 2 Z9 2 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1444-1586 EI 1447-0594 J9 GERIATR GERONTOL INT JI Geriatr. Gerontol. Int. PD OCT PY 2013 VL 13 IS 4 BP 942 EP 948 DI 10.1111/ggi.12035 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 271LE UT WOS:000328392600016 PM 23441847 ER PT J AU Nogueira, RG Bayrlee, A Hirsch, JA Yoo, AJ Copen, WA AF Nogueira, Raul G. Bayrlee, Ahmad Hirsch, Joshua A. Yoo, Albert J. Copen, William A. TI Dynamic Contrast-Enhanced MRA at 1.5 T for Detection of Arteriovenous Shunting Before and After Onyx Embolization of Cerebral Arteriovenous Malformations SO JOURNAL OF NEUROIMAGING LA English DT Article DE Cerebral arteriovenous malformation; Onyx; MRI; TRICKS ID MAGNETIC-RESONANCE ANGIOGRAPHY AB BACKGROUNDConventional non-invasive angiographic techniques for evaluating cerebral Arteriovenous Malformations (cAVMs) after embolization treatment are limited by their inability to acquire time-resolved images. We describe the use of dynamic contrast-enhanced magnetic resonance angiography (MRA) in the evaluation of residual arteriovenous shunting in cAVMs following Onyx embolization. METHODSSix subjects who underwent multimodal MR imaging including dynamic MRA after different stages of endovascular treatment with Onyx were included. Each MRA was assessed for the presence of residual arteriovenous shunting. The results were compared with digital subtraction angiography (DSA). RESULTSMean age was 41 years (range, 25-63) and the mean maximum AVM diameter was 5.3 cm (range, 4.7-6.0). Fourteen dynamic MRA were performed using a 1.5 T scanner. Arteriovenous shunting was detected in thirteen of fourteen patients by both dynamic MRA and DSA, with complete agreement between the two techniques. The only MRA without detectable residual arteriovenous shunting was for a subject who had complete treatment with no residual cAVM as confirmed by the DSA images. CONCLUSIONSDynamic contrast-enhanced MRA is a promising non-invasive modality in identifying residual arteriovenous shunting after different stages of AVM embolization, achieving 100% agreement in this small study. Embolization with Onyx caused no significant image artifact. C1 [Nogueira, Raul G.; Bayrlee, Ahmad] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Hirsch, Joshua A.; Yoo, Albert J.; Copen, William A.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Nogueira, Raul G.] Emory Univ, Sch Med, Dept Neurol, Marcus Stroke & Neurosci Ctr,Grady Mem Hosp, Atlanta, GA 30322 USA. [Nogueira, Raul G.] Emory Univ, Sch Med, Dept Neurosurg, Marcus Stroke & Neurosci Ctr,Grady Mem Hosp, Atlanta, GA 30322 USA. [Nogueira, Raul G.] Emory Univ, Sch Med, Dept Radiol, Marcus Stroke & Neurosci Ctr,Grady Mem Hosp, Atlanta, GA 30322 USA. RP Nogueira, RG (reprint author), Emory Fac Off Bldg,80 Jesse Hill Dr SE,Room 398, Atlanta, GA 30303 USA. EM rnoguei@emory.edu FU Penumbra, Inc. FX RGN is a member of the Scientific Advisory Boards (SAB) for Concentric Medical Inc., ev3 Neurovascular Inc., CoAxia Inc., Rapid Medical, Inc., and Neurointervention, Inc. AJY receives a research grant support from Penumbra, Inc. NR 9 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1051-2284 EI 1552-6569 J9 J NEUROIMAGING JI J. Neuroimaging PD OCT PY 2013 VL 23 IS 4 BP 514 EP 517 DI 10.1111/j.1552-6569.2012.00780.x PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 269XM UT WOS:000328277200009 PM 23317169 ER PT J AU Matreyek, KA Engelman, A AF Matreyek, Kenneth A. Engelman, Alan TI Viral and Cellular Requirements for the Nuclear Entry of Retroviral Preintegration Nucleoprotein Complexes SO VIRUSES-BASEL LA English DT Review DE HIV; lentivirus; nuclear import; nuclear pore complex; capsid; TNPO3; CPSF6; NUP153; NUP358 ID IMMUNODEFICIENCY-VIRUS TYPE-1; MURINE LEUKEMIA-VIRUS; CENTRAL DNA FLAP; REVERSE TRANSCRIPTION COMPLEXES; HIV-1 MATRIX PROTEIN; INTEGRATION IN-VIVO; C-TERMINAL DOMAIN; PORE COMPLEX; NONDIVIDING CELLS; CAPSID PROTEIN AB Retroviruses integrate their reverse transcribed genomes into host cell chromosomes as an obligate step in virus replication. The nuclear envelope separates the chromosomes from the cell cytoplasm during interphase, and different retroviral groups deal with this physical barrier in different ways. Gammaretroviruses are dependent on the passage of target cells through mitosis, where they are believed to access chromosomes when the nuclear envelope dissolves for cell division. Contrastingly, lentiviruses such as HIV-1 infect non-dividing cells, and are believed to enter the nucleus by passing through the nuclear pore complex. While numerous virally encoded elements have been proposed to be involved in HIV-1 nuclear import, recent evidence has highlighted the importance of HIV-1 capsid. Furthermore, capsid was found to be responsible for the viral requirement of various nuclear transport proteins, including transportin 3 and nucleoporins NUP153 and NUP358, during infection. In this review, we describe our current understanding of retroviral nuclear import, with emphasis on recent developments on the role of the HIV-1 capsid protein. C1 [Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM matreyek@fas.harvard.edu; alan_engelman@dfci.harvard.edu OI Matreyek, Kenneth/0000-0001-9149-551X FU NIH [AI052014, GM082251] FX Research in the authors' laboratory is supported by NIH grants AI052014 and GM082251. NR 189 TC 40 Z9 40 U1 0 U2 12 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD OCT PY 2013 VL 5 IS 10 BP 2483 EP 2511 DI 10.3390/v5102483 PG 29 WC Virology SC Virology GA 274SL UT WOS:000328626400009 PM 24103892 ER PT J AU Wang, J Boutin, KG Abdulhadi, O Personnat, LD Shazly, T Langer, R Channick, CL Borenstein, JT AF Wang, Jane Boutin, Kyle G. Abdulhadi, Omar Personnat, Lyndia D. Shazly, Tarek Langer, Robert Channick, Colleen L. Borenstein, Jeffrey T. TI Fully Biodegradable Airway Stents Using Amino Alcohol-Based Poly(ester amide) Elastomers SO ADVANCED HEALTHCARE MATERIALS LA English DT Article DE airway stents; biodegradable; elastomer; implant; polymer ID TISSUE-ENGINEERING SCAFFOLDS; TRACHEOBRONCHIAL STENT; OBSTRUCTION; TECHNOLOGY; STENOSIS; OUTCOMES; POLYMER; DISEASE; CULTURE AB Airway stents are often used to maintain patency of the tracheal and bronchial passages in patients suffering from central airway obstruction caused by malignant tumors, scarring, and injury. Like most conventional medical implants, they are designed to perform their functions for a limited period of time, after which surgical removal is often required. Two primary types of airway stents are in general use, metal mesh devices and elastomeric tubes; both are constructed using permanent materials, and must be removed when no longer needed, leading to potential complications. This paper describes the development of process technologies for bioresorbable prototype elastomeric airway stents that would dissolve completely after a predetermined period of time or by an enzymatic triggering mechanism. These airway stents are constructed from biodegradable elastomers with high mechanical strength, flexibility and optical transparency. This work combines microfabrication technology with bioresorbable polymers, with the ultimate goal of a fully biodegradable airway stent ultimately capable of improving patient safety and treatment outcomes. C1 [Wang, Jane; Boutin, Kyle G.; Personnat, Lyndia D.; Borenstein, Jeffrey T.] Ctr Biomed Engn, Charles Stark Draper Lab, Cambridge, MA 02139 USA. [Wang, Jane; Langer, Robert] MIT, David H Koch Inst, Cambridge, MA 02139 USA. [Abdulhadi, Omar; Shazly, Tarek] Univ S Carolina, Columbia, SC USA. [Channick, Colleen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Borenstein, JT (reprint author), Ctr Biomed Engn, Charles Stark Draper Lab, Mail Stop 32,555 Technol Sq, Cambridge, MA 02139 USA. EM jborenstein@draper.com FU Draper Laboratory; Center of Integration of Medicine and Innovative Technology [US Army DAMD17-02-2-0006] FX Funding for this work, provided by Draper Laboratory and by the Center of Integration of Medicine and Innovative Technology, Contract Number US Army DAMD17-02-2-0006, is gratefully acknowledged. We are indebted to G. C. Engelmayr, C.J. Bettinger, L. E. Freed, J. Hsiao, M. E. Kolewe and H. S. Park for many useful discussions and assistance with the instrumentation and polymer synthesis. NR 34 TC 7 Z9 8 U1 3 U2 30 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2192-2640 EI 2192-2659 J9 ADV HEALTHC MATER JI Adv. Healthc. Mater. PD OCT PY 2013 VL 2 IS 10 BP 1329 EP 1336 DI 10.1002/adhm.201200348 PG 8 WC Engineering, Biomedical; Nanoscience & Nanotechnology; Materials Science, Biomaterials SC Engineering; Science & Technology - Other Topics; Materials Science GA 264RY UT WOS:000327899400005 PM 23526787 ER PT J AU Namba, T Tian, F Chu, KK Hwang, SY Yoon, KW Byun, S Hiraki, M Mandinova, A Lee, SW AF Namba, Takushi Tian, Fang Chu, Kiki Hwang, So-Young Yoon, Kyoung Wan Byun, Sanguine Hiraki, Masatsugu Mandinova, Anna Lee, Sam W. TI CDIP1-BAP31 Complex Transduces Apoptotic Signals from Endoplasmic Reticulum to Mitochondria under Endoplasmic Reticulum Stress SO CELL REPORTS LA English DT Article ID UNFOLDED PROTEIN RESPONSE; CELL-DEATH; BAP31 COMPLEX; BAX; BCL-2; PROCASPASE-8; IRE1-ALPHA; NETWORK AB Resolved endoplasmic reticulum (ER) stress response is essential for intracellular homeostatic balance, but unsettled ER stress can lead to apoptosis. Here, we show that a proapoptotic p53 target, CDIP1, acts as a key signal transducer of ER-stress-mediated apoptosis. We identify B-cell-receptor-associated protein 31 (BAP31) as an interacting partner of CDIP1. Upon ER stress, CDIP1 is induced and enhances an association with BAP31 at the ER membrane. We also show that CDIP1 binding to BAP31 is required for BAP31 cleavage upon ER stress and for BAP31-Bcl-2 association. The recruitment of Bcl-2 to the BAP31-CDIP1 complex, as well as CDIP1-dependent truncated Bid (tBid) and caspase-8 activation, contributes to BAX oligomerization. Genetic knockout of CDIP1 in mice leads to impaired response to ER-stress-mediated apoptosis. Altogether, our data demonstrate that the CDIP1/BAP31-mediated regulation of mitochondrial apoptosis pathway represents a mechanism for establishing an ER-mitochondrial crosstalk for ER-stress-mediated apoptosis signaling. C1 [Namba, Takushi; Tian, Fang; Chu, Kiki; Hwang, So-Young; Yoon, Kyoung Wan; Byun, Sanguine; Hiraki, Masatsugu; Mandinova, Anna; Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Mandinova, Anna; Lee, Sam W.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. RP Lee, SW (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM swlee@partners.org FU National Institutes of Health [CA142805, CA080058, CA127247]; Japan Society for the Promotion of Science; AACR-Bristol-Myers Squibb Oncology Scholar-in-Training grant; Korean Government Research Foundation [KRF-2008-357-E00023] FX LC-MS/MS analysis was performed by the Taplin Biological Mass Spectrometry Facility of Harvard Medical School. We thank S. Aaronson for helpful advice and suggestions during the project. This work was partially supported by National Institutes of Health grants CA142805, CA080058, and CA127247. T.N. was supported by a fellowship for research abroad from Japan Society for the Promotion of Science and is a recipient of an AACR-Bristol-Myers Squibb Oncology Scholar-in-Training grant. S.-Y.H. was supported by the Korean Government Research Foundation (KRF-2008-357-E00023). NR 25 TC 20 Z9 22 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD OCT PY 2013 VL 5 IS 2 BP 331 EP 339 DI 10.1016/j.celrep.2013.09.020 PG 9 WC Cell Biology SC Cell Biology GA 269SU UT WOS:000328263000006 PM 24139803 ER PT J AU Huang, YY Nagata, K Tedford, CE McCarthy, T Hamblin, MR AF Huang, Ying-Ying Nagata, Kazuya Tedford, Clark E. McCarthy, Thomas Hamblin, Michael R. TI Low-level laser therapy (LLLT) reduces oxidative stress in primary cortical neurons in vitro SO JOURNAL OF BIOPHOTONICS LA English DT Article ID TRAUMATIC BRAIN-INJURY; NEAR-INFRARED LIGHT; TERM NEUROLOGICAL DEFICITS; RAT-LIVER MITOCHONDRIA; BIPHASIC DOSE-RESPONSE; CYTOCHROME-C-OXIDASE; HELIUM-NEON LASER; DIFFERENT WAVELENGTHS; DOPAMINERGIC-NEURONS; COGNITIVE DEFICITS C1 [Huang, Ying-Ying; Nagata, Kazuya; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Huang, Ying-Ying; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Huang, Ying-Ying] Guangxi Med Univ, Dept Pathol, Nanning, Guangxi, Peoples R China. [Nagata, Kazuya] Univ Tokyo, Grad Sch Med, Tokyo 1138654, Japan. [Tedford, Clark E.; McCarthy, Thomas] PhotoThera Inc, Carlsbad, CA USA. [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, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU Photothera Inc; NIH [R01AI050875]; Center for Integration of Medicine and Innovative Technology [DAMD17-02-2-0006]; CDMRP Program in TBI [W81XWH-09-1-0514]; Air Force Office of Scientific Research [FA9950-04-1-0079] FX This work was supported by sponsored research funding from Photothera Inc and by NIH grant R01AI050875, Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006), CDMRP Program in TBI (W81XWH-09-1-0514) and Air Force Office of Scientific Research (FA9950-04-1-0079) NR 80 TC 26 Z9 27 U1 0 U2 7 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1864-063X EI 1864-0648 J9 J BIOPHOTONICS JI J. Biophotonics PD OCT PY 2013 VL 6 IS 10 SI SI BP 829 EP 838 PG 10 WC Biochemical Research Methods; Biophysics; Optics SC Biochemistry & Molecular Biology; Biophysics; Optics GA 264NL UT WOS:000327884800009 PM 23281261 ER PT J AU Sperandio, FF Giudice, FS Correa, L Pinto, DS Hamblin, MR de Sousa, SCOM AF Sperandio, Felipe F. Giudice, Fernanda S. Correa, Luciana Pinto, Decio S., Jr. Hamblin, Michael R. de Sousa, Suzana C. O. M. TI Low-level laser therapy can produce increased aggressiveness of dysplastic and oral cancer cell lines by modulation of Akt/mTOR signaling pathway SO JOURNAL OF BIOPHOTONICS LA English DT Article ID IN-VITRO; TYROSINE KINASE; IRRADIATION; HEAD; INHIBITION; PROLIFERATION; MUCOSITIS; MECHANISM; MELANOMA; PROTEIN C1 [Sperandio, Felipe F.; Giudice, Fernanda S.; Correa, Luciana; Pinto, Decio S., Jr.; de Sousa, Suzana C. O. M.] Univ Sao Paulo, Sch Dent, Dept Oral Pathol, BR-05508000 Sao Paulo, Brazil. [Sperandio, Felipe F.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Sperandio, Felipe F.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Sperandio, FF (reprint author), Univ Sao Paulo, Sch Dent, Dept Oral Pathol, 2227 Prof Lineu Prestes Av,Cidade Univ, BR-05508000 Sao Paulo, Brazil. EM sperandio@usp.br RI Correa, Luciana/H-3875-2012; Sousa, Suzana/H-6154-2012; OI Hamblin, Michael/0000-0001-6431-4605 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2009/08452-2, 2009/16183-1]; US NIH [R01AI050875] FX Contract grant sponsor: Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - Grant numbers: 2009/08452-2 and 2009/16183-1. MR Hamblin was supported by US NIH grant R01AI050875. NR 55 TC 17 Z9 17 U1 1 U2 5 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1864-063X EI 1864-0648 J9 J BIOPHOTONICS JI J. Biophotonics PD OCT PY 2013 VL 6 IS 10 SI SI BP 839 EP 847 PG 9 WC Biochemical Research Methods; Biophysics; Optics SC Biochemistry & Molecular Biology; Biophysics; Optics GA 264NL UT WOS:000327884800010 PM 23554211 ER PT J AU Keuthen, NJ Fama, J Altenburger, EM Allen, A Raff, A Pauls, D AF Keuthen, Nancy J. Fama, Jeanne Altenburger, Erin M. Allen, Amanda Raff, Anna Pauls, David TI Family environment in adolescent trichotillomania SO JOURNAL OF OBSESSIVE-COMPULSIVE AND RELATED DISORDERS LA English DT Article DE Trichotillomania; Hair pulling; Family environment ID OBSESSIVE-COMPULSIVE DISORDER; EXPRESSED EMOTION; CHILDREN; ANXIETY; PSYCHOPATHOLOGY; DEPRESSION AB We examined family environment variables and parenting stress in a cohort of adolescents with trichotillomania (TTM; N=49), their parents (N=55) and matched control adolescents (N=23) and their parents (N=23). TTM youth vs. controls endorsed significantly more expression of anger, aggression and conflict in their families and less family support on the Family Relationship Index (FRI) of the Family Environment Scale (FES). Pulling distress but not severity was correlated with these variables. Greater pulling severity, distress or both were correlated with impairment on the cohesion subscale of the FES and the task accomplishment and affective expression subscales of the Family Assessment Measure (FAM). Mothers of TTM youth vs. controls endorsed more anxiety, depression and anger, plus more total parenting stress and problems in their offspring on the Stress Index for Parents of Adolescents (SIPA). On the FES, mothers of TTM youth vs. controls reported less emphasis on intellectual and cultural orientation and less organization in the family. TTM youth and their mothers were discordant in their ratings of several family environment variables. These findings warrant further study and merit attention when designing treatment interventions for adolescents with TTM. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Keuthen, Nancy J.; Fama, Jeanne; Altenburger, Erin M.; Pauls, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Allen, Amanda] Boston Univ, Sch Social Work, Boston, MA 02215 USA. [Raff, Anna] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Keuthen, NJ (reprint author), Massachusetts Gen Hosp, Trichotillomania Clin, Simches Res Bldg,Fl 2,185 Cambridge St, Boston, MA 02114 USA. EM nkeuthen@partners.org FU Greater Kansas City Foundation FX This research was financially supported by a grant from the Greater Kansas City Foundation. We would like to express our gratitude to Liz Loerke, Nicole Dacuyan and Brianne Campbell for their assistance with data collection and input. We would also like to express our thanks to Lisa Osiecki for her assistance with database management and to Irina Kasarskis for support with statistical analysis. NR 32 TC 1 Z9 1 U1 6 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2211-3649 J9 J OBSESS-COMPULS REL JI J. Obsessive-Compuls. Relat. Disord. PD OCT PY 2013 VL 2 IS 4 BP 366 EP 374 DI 10.1016/j.jocrd.2013.07.001 PG 9 WC Psychiatry SC Psychiatry GA 269JR UT WOS:000328238100002 ER PT J AU Wamsley, MA Julian, KA O'Sullivan, P McCance-Katz, EF Batki, SL Satre, DD Satterfield, J AF Wamsley, Maria A. Julian, Katherine A. O'Sullivan, Patricia McCance-Katz, Elinore F. Batki, Steven L. Satre, Derek D. Satterfield, Jason TI Team-Based Learning Exercise Efficiently Teaches Brief Intervention Skills to Medicine Residents SO SUBSTANCE ABUSE LA English DT Article DE Curriculum development and evaluation; graduate medical education; substance use; team-based learning ID PATIENTS ALCOHOL-USE; PRIMARY-CARE; SUBSTANCE-ABUSE; TREATMENT SBIRT; DRUG-USE; IMPACT; CURRICULUM; EDUCATION; PERFORMANCE; SETTINGS AB Background: Evaluations of substance use screening and brief intervention (SBI) curricula typically focus on learner attitudes and knowledge, although effects on clinical skills are of greater interest and utility. Moreover, these curricula often require large amounts of training time and teaching resources. This study examined whether a 3-hour SBI curriculum for internal medicine residents utilizing a team-based learning (TBL) format is effective for SBI skills as measured by a standardized patient (SP) assessment. Methods: A waitlist-controlled design was employed. Results: Twenty-four postgraduate year 2 (PGY-2) and PGY-3 residents participated in a SP assessment prior to the TBL session (waitlist control group) and 32 participated in a SP assessment after the TBL session (intervention group). The intervention residents demonstrated better brief intervention skills than waitlist control residents, but there were no differences between the groups in screening and assessment skills. Residents receiving the TBL curriculum prior to the SP assessment reported increased confidence in all SBI skills. Conclusion: Findings indicate that a brief educational intervention can improve brief intervention skills. However, more intensive education may be needed to improve substance use screening and assessment. C1 [Wamsley, Maria A.; Julian, Katherine A.; O'Sullivan, Patricia; Satterfield, Jason] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [McCance-Katz, Elinore F.; Batki, Steven L.; Satre, Derek D.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Batki, Steven L.] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. [Satre, Derek D.] Kaiser Permanente, Div Res, San Francisco, CA USA. RP Wamsley, MA (reprint author), Univ Calif San Francisco, Div Gen Internal Med, 1545 Divisadero St,Room 322,Campus Box 0320, San Francisco, CA 94143 USA. EM maria.wamsley@ucsf.edu RI Herring, Anna/L-7859-2014 FU SAMHSA [U79T1020295] FX This research was funded by SAMHSA grant U79T1020295 awarded to Dr. Satterfield. NR 41 TC 4 Z9 4 U1 1 U2 8 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. PD OCT 1 PY 2013 VL 34 IS 4 BP 344 EP 349 DI 10.1080/08897077.2013.787958 PG 6 WC Substance Abuse SC Substance Abuse GA 269LB UT WOS:000328241700003 PM 24159904 ER PT J AU Wakeman, SE Baggett, MV Pham-Kanter, G Campbell, EG AF Wakeman, Sarah E. Baggett, Meridale V. Pham-Kanter, Genevieve Campbell, Eric G. TI Internal Medicine Residents' Training in Substance Use Disorders: A Survey of the Quality of Instruction and Residents' Self-Perceived Preparedness to Diagnose and Treat Addiction SO SUBSTANCE ABUSE LA English DT Article DE Addiction; medical education; preparedness; residency training; substance use disorder ID PRIMARY-CARE; DRUG-USERS; PREVALENCE; PHYSICIANS; ALCOHOL; BUPRENORPHINE; DISCHARGE; ADVICE; ABUSE AB Background: Resident physicians are the direct care providers for many patients with addiction. This study assesses residents' self-perceived preparedness to diagnose and treat addiction, measures residents' perceptions of the quality of addictions instruction, and evaluates basic knowledge of addictions. Methods: A survey was e-mailed to 184 internal medicine residents at Massachusetts General Hospital in May 2012. Results: Responses were obtained from 55% of residents. Residents estimated that 26% of inpatients they cared for met criteria for a substance use disorder (SUD). Twenty-five percent of residents felt unprepared to diagnose and 62% felt unprepared to treat addiction. Only 13% felt very prepared to diagnose addiction. No residents felt very prepared to treat addiction. Preparedness to diagnose or treat addiction did not differ significantly across postgraduate year (PGY) level. Fifty-five percent rated the overall instruction in addictions as poor or fair. Seventy-two percent of residents rated the quality of addictions training as poor or fair in the outpatient clinical setting, and 56% in the inpatient setting. No resident answered all 6 knowledge questions correctly. Slightly more than half correctly identified the mechanism of buprenorphine and 19% correctly answered a question about naltrexone. Nine percent of residents responded that someone had expressed concern about the respondent's substance use. Conclusions: Despite providing care for a substantial population with addiction, the majority of internal medicine residents in this study feel unprepared to treat SUDs. More than half rate the quality of addictions instruction as fair or poor. Structured and comprehensive addictions curriculum and faculty development are needed to address the deficiencies of the current training system. C1 [Wakeman, Sarah E.; Baggett, Meridale V.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Wakeman, Sarah E.; Campbell, Eric G.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Pham-Kanter, Genevieve; Campbell, Eric G.] Mongan Inst Hlth Policy, Boston, MA USA. [Pham-Kanter, Genevieve] Harvard Univ, Edmond J Safra Ctr Eth, Cambridge, MA 02138 USA. [Pham-Kanter, Genevieve] Univ Colorado, Colorado Sch Publ Hlth, Dept Hlth Syst Management & Policy, Denver, CO 80202 USA. RP Wakeman, SE (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRB 740, Boston, MA 02114 USA. EM swakeman@partners.org OI Pham-Kanter, Genevieve/0000-0002-3044-7829 NR 18 TC 17 Z9 17 U1 1 U2 8 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. PD OCT 1 PY 2013 VL 34 IS 4 BP 363 EP 370 DI 10.1080/08897077.2013.797540 PG 8 WC Substance Abuse SC Substance Abuse GA 269LB UT WOS:000328241700006 PM 24159907 ER PT J AU Drucker, A Arnason, T Yan, SR Aljawad, M Thompson, K Huang, WY AF Drucker, Arik Arnason, Thomas Yan, Sen Rong Aljawad, Mohammed Thompson, Kara Huang, Weei-Yuarn TI Ephrin B2 Receptor and Microsatellite Status in Lymph Node-Positive Colon Cancer Survival SO TRANSLATIONAL ONCOLOGY LA English DT Article ID COLORECTAL-CANCER; ADJUVANT THERAPY; COST-EFFECTIVENESS; TISSUE MICROARRAY; CETUXIMAB; EPHB2; CHEMOTHERAPY; EXPRESSION; INTEGRINS; ADHESION AB BACKGROUND: Ephrin B2 receptor (EphB2) is a target of the canonical wnt pathway implicated in colorectal carcinogenesis, and its down-regulation may be associated with adverse prognosis. We evaluated its prognostic value in resected colon cancer stratified by microsatellite status and other clinicopathologic characteristics. METHODS: We identified all cases of resected stage III colon cancer from 1995 to 2009 managed in the Capital Health district of Nova Scotia. Tissue microarrays were constructed and immunohistochemistry (IHC) for tumor EphB2 staining assigned into quartiles. Microsatellite status was evaluated by IHC for MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2). Microsatellite stable tumors were defined as both MLH1/MSH2 (+/+); tumors staining otherwise were classified with microsatellite instability (MSI-H). Primary and secondary outcomes were disease-free survival (DFS) and overall survival (OS), respectively. RESULTS: We identified 159 cases with sufficient tissue for microarray analysis having a median follow-up of 3.47 years (range, 0.14-14). Median age was 61, 52% were male, 40% had an event, and 29% died. MSI-H was present in 18 (13%). Univariate analysis of EphB2 expression on DFS and OS showed a hazard ratio (HR) of 2.00 (P = .01) and 2.14 (P = .03), respectively. Multivariate analysis of EphB2 expression on DFS and OS showed an HR of 2.24 and 2.23, respectively, with tumor IHC <= 50%. CONCLUSIONS: In this cohort, decreased EphB2 expression was an independent prognostic factor for recurrence and death and may have prognostic relevance in tumors with MSI-H. However, this would require prospective validation in a larger study. C1 [Drucker, Arik; Arnason, Thomas; Thompson, Kara; Huang, Weei-Yuarn] Dalhousie Univ, Capital Hlth, Halifax, NS B3H 1V8, Canada. [Drucker, Arik] Dalhousie Univ, Dept Med, Div Med Oncol, Halifax, NS B3H 1V8, Canada. [Arnason, Thomas; Huang, Weei-Yuarn] Dalhousie Univ, Dept Pathol & Lab Med, Halifax, NS B3H 1V8, Canada. [Arnason, Thomas] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Arnason, Thomas] Harvard Univ, Sch Med, Boston, MA USA. [Yan, Sen Rong] Dr Everett Chalmers Hosp, Fredericton, NB, Canada. [Aljawad, Mohammed] Univ Western Ontario, London Hlth Sci Ctr, London, ON, Canada. [Aljawad, Mohammed] Univ Western Ontario, Div Gastroenterol, London, ON, Canada. [Thompson, Kara] Dalhousie Univ, Res Methods Unit, Halifax, NS B3H 1V8, Canada. [Thompson, Kara] Dalhousie Univ, Dept Med, Halifax, NS B3H 1V8, Canada. RP Huang, WY (reprint author), Dalhousie Univ, Capital Hlth, 5788 Univ Ave, Halifax, NS B3H 1V8, Canada. EM huangw@cdha.nshealth.ca FU Capital Health Category 3 Competitive Research grant; Department of Pathology and Laboratory Medicine, Halifax; Queen Elizabeth II Health Sciences Centre, Halifax; Nova Scotia FX This study was funded by the Capital Health Category 3 Competitive Research grant and the Department of Pathology and Laboratory Medicine, Queen Elizabeth II Health Sciences Centre, both in Halifax, Nova Scotia. None of the authors have any financial or other conflicts of interest to disclose. NR 28 TC 0 Z9 0 U1 0 U2 0 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1944-7124 EI 1936-5233 J9 TRANSL ONCOL JI Transl. Oncol. PD OCT PY 2013 VL 6 IS 5 BP 520 EP 527 DI 10.1593/tlo.13385 PG 8 WC Oncology SC Oncology GA 271AQ UT WOS:000328362800003 PM 24151532 ER PT J AU Engineer, DR Burney, BO Hayes, TG Garcia, JM AF Engineer, Diana R. Burney, Basil O. Hayes, Teresa G. Garcia, Jose M. TI Exposure to ACEI/ARB and beta-Blockers Is Associated with Improved Survival and Decreased Tumor Progression and Hospitalizations in Patients with Advanced Colon Cancer SO TRANSLATIONAL ONCOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; HEART-FAILURE; CELLS; ANGIOGENESIS; PROPRANOLOL; INHIBITION; EXPRESSION; RECEPTOR; MODEL; PROLIFERATION AB BACKGROUND: Advanced colon cancer is associated with weight loss and decreased survival. Studies suggest that angiotensin and beta-adrenergic blockade decrease colon cancer progression and ameliorate weight loss. This study aims to determine whether exposure to beta-adrenoceptor blockers (BBs), angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) is associated with decreased mortality, tumor progression, number of hospitalizations, or weight loss in colorectal cancer. METHODS: Retrospective chart review included patients with advanced colorectal cancer. Survival, stage, hospitalization, cancer progression, cancer treatment, and body weight history were collected. RESULTS: Two hundred sixty-two of 425 new stage III to IV colorectal cancer cases reviewed met the study criteria. Those exposed to ACEI/ARB, BB, or both were more likely to have diabetes, hypertension, and stage III colorectal cancer. Adjusting for age, presence of hypertension and diabetes, and stage, ACEI/ARB + BB exposure was associated with decreased mortality compared to unexposed individuals [hazard ratio (HR) = 0.5, confidence interval (CI) = 0.29-0.85; Cox regression, P =.01]. Fewer total and cancer-related hospitalizations and decreased cancer progression in the ACEI/ARB + BB group versus the unexposed group (HR = 0.59, CI = 0.36-0.99, P =.047) were seen. Exposure did not affect weight changes; furthermore, body weight changes from both prediagnosis and at diagnosis to 6, 12, 18, and 24 months postdiagnosis predicted survival. CONCLUSIONS: We have observed an association between exposure to a combination of ACEI/ ARB + BB and increased survival, decreased hospitalizations, and decreased tumor progression in advanced colorectal cancer. Future studies will be needed to replicate these results and generalize them to broader populations. Determination of causality will require a randomized controlled trial. C1 [Engineer, Diana R.; Burney, Basil O.; Garcia, Jose M.] Michael E DeBakey VA Med Ctr, Div Diabet Endocrinol & Metab, Ctr Translat Res Inflammatory Dis, Houston, TX USA. [Engineer, Diana R.; Garcia, Jose M.] Baylor Coll Med, Houston, TX 77030 USA. [Engineer, Diana R.] St Lukes Episcopal Hosp, Houston, TX 77030 USA. [Hayes, Teresa G.] Baylor Coll Med, Div Hematol & Oncol, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Garcia, Jose M.] Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA. RP Garcia, JM (reprint author), Baylor Coll Med, Div Endocrinol Diabet & Metab, Michael E DeBakey Vet Affairs Med Ctr, Rm 210,Bldg 109,2002 Holcombe Blvd, Houston, TX 77030 USA. EM jgarcia1@bcm.edu FU Veterans Affairs Medical Center (Houston, TX); Department of Veterans Affairs (MERIT awards) [BX000507, CX000174]; National Institutes of Health [AG040583] FX This material is based on the work supported by the Michael E. DeBakey Veterans Affairs Medical Center (Houston, TX), Department of Veterans Affairs (MERIT awards BX000507 and CX000174), and the National Institutes of Health (AG040583) to J.M.G. The authors report no conflicts of interest. NR 32 TC 17 Z9 18 U1 0 U2 2 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1944-7124 EI 1936-5233 J9 TRANSL ONCOL JI Transl. Oncol. PD OCT PY 2013 VL 6 IS 5 BP 539 EP 545 DI 10.1593/tlo.13346 PG 7 WC Oncology SC Oncology GA 271AQ UT WOS:000328362800005 PM 24151534 ER PT J AU Fishman, JA AF Fishman, Jay A. TI Opportunistic Infections-Coming to the Limits of Immunosuppression? SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID ORGAN-TRANSPLANT RECIPIENTS; HEPATITIS-C-VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; MUSCULOSKELETAL TISSUE DONORS; TRANSMITTED VIRAL-INFECTIONS; CYTOMEGALOVIRUS DISEASE; LIVER-TRANSPLANTATION; HETEROLOGOUS IMMUNITY; LUNG TRANSPLANTATION; BLOOD-DONORS AB Possible etiologies of infection in the solid organ recipient are diverse, ranging from common bacterial and viral pathogens to opportunistic pathogens that cause invasive disease only in immunocompromised hosts. The recognition of infectious syndromes in this population is limited by alterations in the clinical manifestations by immunosuppression. The risk of serious infections in the organ transplant patient is determined by the interaction between the patients' recent and distant epidemiological exposures and all factors that contribute to the patient's net state of immune suppression. This risk is altered by antimicrobial prophylaxis and changes in immunosuppressive therapies. In addition to the direct effects of infection, opportunistic infections, and the microbiome may adversely shape the host immune responses with diminished graft and patient survivals. Antimicrobial therapies are more complex than in the normal host with a significant incidence of drug toxicity and a propensity for drug interactions with the immunosuppressive agents used to maintain graft function. Rapid and specific microbiologic diagnosis is essential. Newer microbiologic assays have improved the diagnosis and management of opportunistic infections. These tools coupled with assays that assess immune responses to infection and to graft antigens may allow optimization of management for graft recipients in the future. C1 Harvard Univ, Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, Infect Dis Div,MGH Transplantat Ctr,Med Sch, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, Infect Dis Div,MGH Transplantat Ctr,Med Sch, Boston, MA 02114 USA. EM jfishman@partners.org NR 52 TC 10 Z9 10 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD OCT PY 2013 VL 3 IS 10 AR a015669 DI 10.1101/cshperspect.a015669 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 269XK UT WOS:000328277000004 PM 24086067 ER PT J AU Vashishta, R Soler, ZM Nguyen, SA Schlosser, RJ AF Vashishta, Rishi Soler, Zachary M. Nguyen, Shaun A. Schlosser, Rodney J. TI A systematic review and meta-analysis of asthma outcomes following endoscopic sinus surgery for chronic rhinosinusitis SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE asthma; chronic rhinosinusitis; endoscopic sinus surgery; ESS; FESS ID ALLERGEN-INDUCED RHINITIS; ASPIRIN TRIAD PATIENTS; NASAL POLYPS; INTRANASAL CORTICOSTEROIDS; BRONCHIAL RESPONSIVENESS; TISSUE EOSINOPHILIA; SURGICAL-TREATMENT; MESSENGER-RNA; MILD ASTHMA; PROVOCATION AB BackgroundPatients suffering from both chronic rhinosinusitis (CRS) and asthma demonstrate improved asthma outcomes when upper airway inflammation is controlled with medications. It is unclear if similar benefits exist when the upper airway is treated surgically. This study presents a systematic review and meta-analysis to assess the effects of endoscopic sinus surgery (ESS) on asthma outcomes. MethodsOvid MEDLINE and the Cochrane databases were searched to identify studies examining asthma outcomes in patients with CRS following ESS. Included studies involved a cohort of at least 5 patients and reported at least 1 postoperative asthma outcome. ResultsTwenty-two studies involving a total of 891 patients were identified. Mean follow-up across all studies was 26.4 months. Patients reported improved overall asthma control in 76.1% (95% confidence interval [CI], 71.9% to 80.3%) of cases. The frequency of asthma attacks decreased in 84.8% (95% CI, 76.6% to 93.0%) of patients and the number of hospitalizations decreased in 64.4% (95% CI, 53.3% to 75.6%). Decreased use of oral corticosteroids was seen in 72.8% (95% CI, 67.5% to 78.1%) of patients; inhaled corticosteroid use decreased in 28.5% (95% CI, 22.6% to 34.5%) and bronchodilator use decreased in 36.3% (95% CI, 28.9% to 43.7%) of patients. Mean improvement in predicted forced expiratory volume at 1 second (FEV1) was 1.62%, but was not statistically significant (p = 0.877). ConclusionESS in patients with concomitant bronchial asthma improves clinical asthma outcome measures, but not lung function testing. Difficulty conducting controlled clinical trials of ESS limits the strength of conclusions which can be reached. C1 [Vashishta, Rishi; Soler, Zachary M.; Nguyen, Shaun A.; Schlosser, Rodney J.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, Dept Surg Otolaryngol, Charleston, SC USA. RP Schlosser, RJ (reprint author), Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA. EM schlossr@musc.edu FU Merit Award from the Clinical Sciences Research and Development program of the Department of Veterans Affairs at the Ralph H. Johnson VA Medical Center, Charleston, SC FX Funding sources for the study: Merit Award from the Clinical Sciences Research and Development program of the Department of Veterans Affairs at the Ralph H. Johnson VA Medical Center, Charleston, SC. NR 42 TC 24 Z9 25 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 EI 2042-6984 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD OCT PY 2013 VL 3 IS 10 BP 788 EP 794 DI 10.1002/alr.21182 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 269EG UT WOS:000328223500003 PM 23818462 ER PT J AU Evertts, AG Manning, AL Wang, X Dyson, NJ Garcia, BA Coller, HA AF Evertts, Adam G. Manning, Amity L. Wang, Xin Dyson, Nicholas J. Garcia, Benjamin A. Coller, Hilary A. TI H4K20 methylation regulates quiescence and chromatin compaction SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID HISTONE METHYLTRANSFERASE SET8; CELL-CYCLE PROGRESSION; CONSTITUTIVE HETEROCHROMATIN; GENE-EXPRESSION; S-PHASE; MUSCLE DIFFERENTIATION; MOUSE DEVELOPMENT; POTENTIAL ROLE; DNA-DAMAGE; STEM-CELLS AB The transition between proliferation and quiescence is frequently associated with changes in gene expression, extent of chromatin compaction, and histone modifications, but whether changes in chromatin state actually regulate cell cycle exit with quiescence is unclear. We find that primary human fibroblasts induced into quiescence exhibit tighter chromatin compaction. Mass spectrometry analysis of histone modifications reveals that H4K20me2 and H4K20me3 increase in quiescence and other histone modifications are present at similar levels in proliferating and quiescent cells. Analysis of cells in S, G(2)/M, and G(1) phases shows that H4K20me1 increases after S phase and is converted to H4K20me2 and H4K20me3 in quiescence. Knockdown of the enzyme that creates H4K20me3 results in an increased fraction of cells in S phase, a defect in exiting the cell cycle, and decreased chromatin compaction. Overexpression of Suv4-20h1, the enzyme that creates H4K20me2 from H4K20me1, results in G(2) arrest, consistent with a role for H4K20me1 in mitosis. The results suggest that the same lysine on H4K20 may, in its different methylation states, facilitate mitotic functions in M phase and promote chromatin compaction and cell cycle exit in quiescent cells. C1 [Evertts, Adam G.; Wang, Xin] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. [Manning, Amity L.; Dyson, Nicholas J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp Canc Ctr, Charlestown, MA 02129 USA. [Garcia, Benjamin A.] Univ Penn, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. [Coller, Hilary A.] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. [Coller, Hilary A.] David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. RP Coller, HA (reprint author), Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. EM hcoller@ucla.edu FU American Cancer Society; National Institutes of Health [R01 CA155202]; National Science Foundation Early Faculty CAREER award; National Science Foundation [CBET-0941143]; Office of the Director, National Institutes of Health [DP2OD007447]; National Institute of General Medical Sciences Center of Excellence Grant [P50 GM071508]; Cancer Institute of New Jersey; New Jersey Commission on Cancer Research; National Cancer Institute [1RC1 CA147961-01]; Johnson & Johnson Foundation; National Institutes of Health/National Institute of General Medical Sciences [1R01 GM081686, 1R01 GM086465] FX We thank Eric Neeley (Novus Biologicals) for providing reagents and all of the members of the Coller and Garcia laboratories for helpful discussions. A. L. M. is supported in part by an American Cancer Society Postdoctoral Fellowship. A. L. M. and N.J.D. are supported by National Institutes of Health Grant R01 CA155202. B. A. G. is supported by a National Science Foundation Early Faculty CAREER award, National Science Foundation Grant CBET-0941143, and a grant supported by Award DP2OD007447 from the Office of the Director, National Institutes of Health. H. A. C. is supported by National Institute of General Medical Sciences Center of Excellence Grant P50 GM071508, the Cancer Institute of New Jersey, the New Jersey Commission on Cancer Research, National Cancer Institute 1RC1 CA147961-01, a Focused Funding Grant from the Johnson & Johnson Foundation, and National Institutes of Health/National Institute of General Medical Sciences Grants 1R01 GM081686 and 1R01 GM086465. H. A. C. was a Milton E. Cassel Scholar of the Rita Allen Foundation. NR 72 TC 23 Z9 23 U1 2 U2 16 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD OCT 1 PY 2013 VL 24 IS 19 BP 3025 EP 3037 DI 10.1091/mbc.E12-07-0529 PG 13 WC Cell Biology SC Cell Biology GA 267UH UT WOS:000328123200003 PM 23924899 ER PT J AU Khaleghi, M Lu, WN Dobrev, I Cheng, JT Furlong, C Rosowski, JJ AF Khaleghi, Morteza Lu, Weina Dobrev, Ivo Cheng, Jeffrey Tao Furlong, Cosme Rosowski, John J. TI Digital holographic measurements of shape and three-dimensional sound-induced displacements of tympanic membrane SO OPTICAL ENGINEERING LA English DT Article DE digital holography; middle-ear mechanics; shape and three-dimensional displacement measurements; sound-induced response; thin-shell theory; tympanic membrane ID SURFACE; MOTION AB Acoustically induced vibrations of the tympanic membrane (TM) play a primary role in the hearing process, in that these motions are the initial mechanical response of the ear to airborne sound. Characterization of the shape and three-dimensional (3-D) displacement patterns of the TM is a crucial step to a better understanding of the complicated mechanics of sound reception by the ear. Sound-induced 3-D displacements of the TM are estimated from shape and one-dimensional displacements measured in cadaveric chinchillas using a lensless dual-wavelength digital holography system (DWDHS). The DWDHS consists of laser delivery, optical head, and computing platform subsystems. Shape measurements are performed in double-exposure mode with the use of two wavelengths of a tunable laser, while nanometer-scale displacements are measured along a single sensitivity direction with a constant wavelength. Taking into consideration the geometrical and dimensional constrains imposed by the anatomy of the TM, we combine principles of thin-shell theory together with displacement measurements along a single sensitivity vector and TM surface shape to extract the three principal components of displacement in the full-field-of-view. We test, validate, and identify limitations of this approach via the application of finite element method to artificial geometries. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. C1 [Khaleghi, Morteza; Lu, Weina; Dobrev, Ivo; Furlong, Cosme] Worcester Polytech Inst, Ctr Holog Studies & Laser MicromechaTron, Worcester, MA 01609 USA. [Khaleghi, Morteza; Lu, Weina; Dobrev, Ivo; Furlong, Cosme] Worcester Polytech Inst, Dept Mech Engn, Worcester, MA 01609 USA. [Cheng, Jeffrey Tao; Furlong, Cosme; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Cheng, Jeffrey Tao; Furlong, Cosme; Rosowski, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Khaleghi, M (reprint author), Worcester Polytech Inst, Ctr Holog Studies & Laser MicromechaTron, Worcester, MA 01609 USA. EM mkm@wpi.edu FU National Institute on Deafness and Other Communication Disorders; Mass Eye Ear Infirmary; Worcester Polytechnic Institute, Mechanical Engineering Department FX This work was supported by the National Institute on Deafness and Other Communication Disorders, the Mass Eye & Ear Infirmary, and the Worcester Polytechnic Institute, Mechanical Engineering Department. We would also like to acknowledge the support of all of the members of the Center for Holographic Studies and Laser micro-mechaTronics laboratories and particularly of Peter Hefti and Ellery Harrington. NR 30 TC 15 Z9 15 U1 0 U2 5 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 0091-3286 EI 1560-2303 J9 OPT ENG JI Opt. Eng. PD OCT PY 2013 VL 52 IS 10 AR 101916 DI 10.1117/1.OE.52.10.101916 PG 11 WC Optics SC Optics GA 269PR UT WOS:000328254600021 PM 24790255 ER PT J AU Maia, Q Grandner, MA Findley, J Gurubhagavatula, I AF Maia, Querino Grandner, Michael A. Findley, James Gurubhagavatula, Indira TI Short and long sleep duration and risk of drowsy driving and the role of subjective sleep insufficiency SO ACCIDENT ANALYSIS AND PREVENTION LA English DT Article DE Sleep; Driving; Accidents; Sleep duration; Insufficient sleep; Epidemiology ID MOTOR-VEHICLE CRASH; METAANALYSIS; PERFORMANCE; DEPRIVATION; ADULTS; STATES; APNEA AB Experimental sleep restriction increases sleepiness and impairs driving performance. However, it is unclear whether short sleep duration in the general population is associated with drowsy driving. The goal of the present study was to evaluate whether individuals in the general population who obtained sleep of 6 h or less are more likely to report drowsy driving, and evaluate the role of perceived sleep sufficiency. Data exploring whether subgroups of short sleepers (those who report the most or least unmet sleep need) show different risk profiles for drowsy driving are limited. From the 2009 Behavioral Risk Factor Surveillance System (N = 31,522), we obtained the following self-reported data: (1) sleep duration (<= 5, 6, 7, 8, 9, or >= 10h/night); (2) number of days/week of perceived insufficient sleep; (3) among drivers, yes/no response to: "During the past 30 days, have you ever nodded off or fallen asleep, even just for a brief moment, while driving?" (4) demographics, physical/mental health. Using 7 h/night as reference, logistic regression analyses evaluated whether self-reported sleep duration was associated with drowsy driving. Overall, 3.6% reported drowsy driving. Self-identified short-sleepers reported drowsy driving more often, and long sleepers, less often. Among those who perceived sleep as always insufficient, drowsy driving was reported more often when sleep duration was <= 5 h, 6 h, or >= 10 h. Among those who perceived sleep as always sufficient, drowsy driving was reported more often among <= 5 h and 6 h sleepers. Overall, drowsy driving was common, particularly in self-identified short-sleepers as a whole, as well as subgroups based on sleep insufficiency. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Maia, Querino; Grandner, Michael A.; Findley, James; Gurubhagavatula, Indira] Univ Penn, Ctr Sleep & Circadian Neurobiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Grandner, Michael A.; Findley, James] Univ Penn, Dept Psychiat, Behav Sleep Med Program, Philadelphia, PA 19104 USA. [Gurubhagavatula, Indira] Philadelphia VA Med Ctr, Pulm Crit Care Sleep Sect, Philadelphia, PA USA. RP Grandner, MA (reprint author), Univ Penn, Ctr Sleep & Circadian Neurobiol, 3624 Market St,Suite 205, Philadelphia, PA 19104 USA. EM grandner@upenn.edu FU NCRR NIH HHS [UL1 RR024134, UL1RR024134]; NHLBI NIH HHS [K23 HL110216, K23HL110216]; NIEHS NIH HHS [R21 ES022931, R21ES022931]; NIOSH CDC HHS [R01 OH009149, R01OH009149] NR 23 TC 16 Z9 16 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0001-4575 EI 1879-2057 J9 ACCIDENT ANAL PREV JI Accid. Anal. Prev. PD OCT PY 2013 VL 59 BP 618 EP 622 DI 10.1016/j.aap.2013.07.028 PG 5 WC Ergonomics; Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary; Transportation SC Engineering; Public, Environmental & Occupational Health; Social Sciences - Other Topics; Transportation GA 261SX UT WOS:000327686000071 PM 23973762 ER PT J AU Sano, M Egelko, S Donohue, M Ferris, S Kaye, J Hayes, TL Mundt, JC Sun, CK Paparello, S Aisen, PS AF Sano, Mary Egelko, Susan Donohue, Michael Ferris, Steven Kaye, Jeffrey Hayes, Tamara L. Mundt, James C. Sun, Chung-Kai Paparello, Silvia Aisen, Paul S. CA Alzheimer Disease Cooperative TI Developing Dementia Prevention Trials Baseline Report of the Home-Based Assessment Study SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE Alzheimer disease; clinical trials; in-home assessment; prevention studies ID INSTRUMENT PROJECT; CLINICAL-TRIALS AB This report describes the baseline experience of the multicenter, Home-Based Assessment study, designed to develop methods for dementia prevention trials using novel technologies for test administration and data collection. Nondemented individuals of 75 years of age or more were recruited and evaluated in-person using established clinical trial outcomes of cognition and function, and randomized to one of 3 assessment methodologies: (1) mail-in questionnaire/live telephone interviews [mail-in/phone (MIP)]; (2) automated telephone with interactive voice recognition; and (3) internet-based computer Kiosk. Brief versions of cognitive and noncognitive outcomes were adapted to each methodology and administered at baseline and repeatedly over a 4-year period. Efficiency measures assessed the time from screening to baseline, and staff time required for each methodology. A total of 713 individuals signed consent and were screened; 640 met eligibility and were randomized to one of 3 assessment arms; and 581 completed baseline. Dropout, time from screening to baseline, and total staff time were highest among those assigned to internet-based computer Kiosk. However, efficiency measures were driven by nonrecurring start-up activities suggesting that differences may be mitigated over a long trial. Performance among Home-Based Assessment instruments collected through different technologies will be compared with established outcomes over this 4-year study. C1 [Sano, Mary; Egelko, Susan] Mt Sinai Sch Med, New York, NY USA. [Ferris, Steven] NYU, Langone Med Ctr, New York, NY USA. [Sano, Mary; Egelko, Susan] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Donohue, Michael; Sun, Chung-Kai; Paparello, Silvia; Aisen, Paul S.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Kaye, Jeffrey; Hayes, Tamara L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kaye, Jeffrey] Portland VA Med Ctr, Portland, OR USA. [Mundt, James C.] Ctr Psychol Consultat, Madison, WI USA. [Mundt, James C.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. RP Sano, M (reprint author), James J Peters VA Med Ctr, 130 Kingsbridge Rd,Code 151 Room 1F01, Bronx, NY 10468 USA. EM mary.sano@mssm.edu OI Kaye, Jeffrey/0000-0002-9971-3478; Ferris, Steven/0000-0001-8641-6223 FU NIA [U01AG10483, P50AG005138, P30AG008051, P30AG024978, P30AG08017]; Intel Corporation FX Supported by the following NIA Grants: U01AG10483, P50AG005138, P30AG008051, and P30AG024978. Development of the Kiosk and MedTracker was supported in part by Grants from NIA (P30AG024978; P30AG08017) and Intel Corporation. NR 18 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 EI 1546-4156 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD OCT-DEC PY 2013 VL 27 IS 4 BP 356 EP 362 DI 10.1097/WAD.0b013e3182769c05 PG 7 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 262NR UT WOS:000327742800010 PM 23151596 ER PT J AU Torchiana, DF Colton, DG Rao, SK Lenz, SK Meyer, GS Ferris, TG AF Torchiana, David F. Colton, Deborah G. Rao, Sandhya K. Lenz, Sarah K. Meyer, Gregg S. Ferris, Timothy G. TI INNOVATION PROFILE Massachusetts General Physicians Organization's Quality Incentive Program Produces Encouraging Results SO HEALTH AFFAIRS LA English DT Article ID OF-CARE; HEALTH-CARE; PERFORMANCE; PAY; DECISION; SUPPORT AB Physicians are increasingly becoming salaried employees of hospitals or large physician groups. Yet few published reports have evaluated provider-driven quality incentive programs for salaried physicians. In 2006 the Massachusetts General Physicians Organization began a quality incentive program for its salaried physicians. Eligible physicians were given performance targets for three quality measures every six months. The incentive payments could be as much as 2 percent of a physician's annual income. Over thirteen six-month terms, the program used 130 different quality measures. Although quality-of-care improvements and cost reductions were difficult to calculate, anecdotal evidence points to multiple successes. For example, the program helped physicians meet many federal health information technology meaningful-use criteria and produced $15.5 million in incentive payments. The program also facilitated the adoption of an electronic health record, improved hand hygiene compliance, increased efficiency in radiology and the cancer center, and decreased emergency department use. The program demonstrated that even small incentives tied to carefully structured metrics, priority setting, and clear communication can help change salaried physicians' behavior in ways that improve the quality and safety of health care and ease the physicians' sense of administrative burden. C1 [Torchiana, David F.; Colton, Deborah G.; Rao, Sandhya K.; Ferris, Timothy G.] MGPO, Boston, MA USA. [Torchiana, David F.; Rao, Sandhya K.; Ferris, Timothy G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lenz, Sarah K.] MGPO, Phys Incent Programs, Boston, MA USA. [Meyer, Gregg S.] Dartmouth Hitchcock Med Ctr, Hanover, NH USA. RP Torchiana, DF (reprint author), MGPO, Boston, MA USA. EM dcolton@partners.org NR 23 TC 9 Z9 9 U1 0 U2 3 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD OCT PY 2013 VL 32 IS 10 BP 1748 EP 1756 DI 10.1377/hlthaff.2013.0377 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 250GG UT WOS:000326837900009 PM 24101064 ER PT J AU Herring, AA Johnson, B Ginde, AA Camargo, CA Feng, L Alter, HJ Hsia, R AF Herring, Andrew A. Johnson, Brian Ginde, Adit A. Camargo, Carlos A. Feng, Lin Alter, Harrison J. Hsia, Renee TI High-Intensity Emergency Department Visits Increased In California, 2002-09 SO HEALTH AFFAIRS LA English DT Article ID UNITED-STATES; CARE-UNIT; ADMISSIONS; TRENDS; IMPACT AB Increasing use of the emergency department (ED) is well documented, but little is known about the type and severity of ED visits or their distribution across safety-net and non-safety-net hospitals. We examined the rates of high-intensity ED visits-characterized by their use of advanced imaging, consultations with specialists, the evaluation of multiple systems, and highly complex medical decision making-by patients with a severe, potentially life-threatening illness in California from 2002 through 2009. Total annual ED visits increased by 25 percent, from 9.0 million to 11.3 million, but high-intensity ED visits nearly doubled, increasing 87 percent from 778,000 to 1.5 million per year. The percentage of ED visits with high-intensity care increased from 9 percent to 13 percent (a relative increase of 44 percent). Annual ED admissions increased by 39 percent overall; most of this increase was attributable to high-intensity ED admissions, which increased by 88 percent. Safety-net EDs experienced an increase in high-intensity visits of 157 percent, compared to an increase of 61 percent at non-safety-net EDs. These findings suggest a trend toward intensification of ED care, particularly at safety-net hospitals, whose patients may have limited access to care outside the ED. C1 [Herring, Andrew A.; Johnson, Brian; Alter, Harrison J.] Alameda Hlth Syst, Highland Hosp, Oakland, CA USA. [Ginde, Adit A.] Univ Colorado, Dept Emergency Med, Sch Med, Aurora, CO USA. [Camargo, Carlos A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Camargo, Carlos A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Feng, Lin] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA USA. [Alter, Harrison J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hsia, Renee] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. RP Herring, AA (reprint author), Alameda Hlth Syst, Highland Hosp, Oakland, CA USA. EM aherring@alamedahealthsystem.org RI bebarta, vikhyat/K-3476-2015; Siry, Bonnie/D-7189-2017 FU National Center for Research Resources, National Institutes of Health [KL2 RR024130]; Robert Wood Johnson Foundation Physician Faculty Scholars FX The research reported here was supported by Grant No. KL2 RR024130 from the National Center for Research Resources, National Institutes of Health, to the Clinical and Translational Science Institute at the University of California, San Francisco, and by the Robert Wood Johnson Foundation Physician Faculty Scholars. The article's contents are solely the responsibility of the authors and do not necessarily represent the official views of any of the funding agencies. NR 39 TC 3 Z9 3 U1 0 U2 2 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD OCT PY 2013 VL 32 IS 10 BP 1811 EP 1819 DI 10.1377/hlthaff.2013.0397 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 250GG UT WOS:000326837900018 PM 24101073 ER PT J AU Anderson, EC Dryman, MT Worthington, J Hoge, EA Fischer, LE Pollack, MH Barrett, LF Simon, NM AF Anderson, Eric C. Dryman, M. Taylor Worthington, John Hoge, Elizabeth A. Fischer, Laura E. Pollack, Mark H. Barrett, Lisa Feldman Simon, Naomi M. TI Smiles may go unseen in generalized social anxiety disorder: Evidence from binocular rivalry for reduced visual consciousness of positive facial expressions SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Visual perception; Motivation and emotion; Psychological disorder's; Affective disorders; Neuroses and anxiety disorders ID THREATENING FACES; PERCEPTION; PHOBIA; BIAS; IMPACT AB Research has demonstrated increased attention to negative social cues and reduced attention to positive social cues in generalized social anxiety disorder (GSAD), but little is known about whether GSAD also involves differences in lower levels of visual processing. This study explored visual experience in GSAD compared to participants with generalized anxiety disorder (GAD) and healthy controls using binocular rivalry. Participants were presented with dissimilar images to each eye, and the two images competed for perceptual dominance. Consistent with the hypothesis that GSAD involves a reduced visual salience for positive social cues, we found that smiling faces were dominant for significantly shorter durations in GSAD compared to GAD and controls. Contrasting with our hypothesis of greater visual salience of negative social cues, we found no difference in negative stimuli salience. These findings are consistent with the broader view that a perceiver's affective state directly influences the content of visual consciousness. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Anderson, Eric C.; Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Dryman, M. Taylor; Worthington, John; Hoge, Elizabeth A.; Fischer, Laura E.; Barrett, Lisa Feldman; Simon, Naomi M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. [Pollack, Mark H.] Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. RP Simon, NM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM NSIMON@partners.org RI Hoge, Elizabeth/H-5879-2012; OI Hoge, Elizabeth/0000-0002-5513-2292; Anderson, Eric/0000-0002-4215-6308 NR 42 TC 6 Z9 6 U1 2 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 EI 1873-7897 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD OCT PY 2013 VL 27 IS 7 BP 619 EP 626 DI 10.1016/j.janxdis.2013.07.004 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 261ST UT WOS:000327685600001 PM 24064330 ER PT J AU White, S Acierno, R Ruggiero, KJ Koenen, KC Kilpatrick, DG Galea, S Gelernter, J Williamson, V McMichael, O Vladimirov, VI Amstadter, AB AF White, Simone Acierno, Ron Ruggiero, Kenneth J. Koenen, Karestan C. Kilpatrick, Dean G. Galea, Sandro Gelernter, Joel Williamson, Vernell McMichael, Omari Vladimirov, Vladimir I. Amstadter, Ananda B. TI Association of CRHR1 variants and posttraumatic stress symptoms in hurricane exposed adults SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Posttraumatic stress disorder; CRHR1; HPA axis; Disasters; Trauma ID POPULATION GROUP ASSIGNMENT; DISORDER SYMPTOMS; COMBAT VETERANS; TRAUMATIC EVENT; RECEPTOR GENE; GENOTYPE DATA; RISK; TWIN; DEPRESSION; MARKERS AB Posttraumatic stress disorder (PTSD) is a moderately heritable anxiety disorder that may develop after exposure to trauma. However, only few genetic variants that relate to PTSD have been studied. This study examined the relationship between 12 single nucleotide polymorphisms (SNPs) in the corticotropin-releasing hormone receptor 1 gene (CRHR1) and post-disaster PTSD symptoms and diagnosis in adults exposed to 2004 Florida hurricanes. CRHR1 regulates the hypothalamic-pituitary-adrenal (HPA) axis; dysregulation of the HPA axis is characteristic of stress phenotypes. Final analyses were conducted in the European-American (EA) subsample (n = 564) due to population stratification. After correction for multiple testing, rs12938031 and rs4792887 remained associated with post-hurricane PTSD symptoms. Additionally, rs12938031 was associated with post-hurricane diagnosis of PTSD. This study is the first to examine CRHR1 in relation to PTSD in adults, and provides evidence for the importance of CRHR1 variation in the etiology of PTSD. Although results are preliminary and require replication, they justify follow-up efforts to characterize how this gene relates to PTSD. (C) 2013 Elsevier Ltd. All rights reserved. C1 [White, Simone; Williamson, Vernell; McMichael, Omari; Vladimirov, Vladimir I.; Amstadter, Ananda B.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA. [Acierno, Ron; Ruggiero, Kenneth J.; Kilpatrick, Dean G.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Acierno, Ron; Ruggiero, Kenneth J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Koenen, Karestan C.; Galea, Sandro] Columbia Univ, Dept Epidemiol, New York, NY USA. [Gelernter, Joel] Yale Univ, Sch Med, Div Human Genet Psychiat, New Haven, CT USA. RP Amstadter, AB (reprint author), Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, 800 E Leigh St,Biotech 1,POB 980126, Richmond, VA 23298 USA. EM slw257@cornell.edu; abamstadter@vcu.edu FU NIAAA NIH HHS [R01 AA020179]; NIGMS NIH HHS [R25 GM089614]; NIMH NIH HHS [R21 MH074469]; PHS HHS [NIGMS 089614, NIMH 05220] NR 47 TC 14 Z9 15 U1 3 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 EI 1873-7897 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD OCT PY 2013 VL 27 IS 7 BP 678 EP 683 DI 10.1016/j.janxdis.2013.08.003 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 261ST UT WOS:000327685600008 PM 24077033 ER PT J AU Gutner, CA Nillni, YI Suvak, M Wiltsey-Stirman, S Resick, PA AF Gutner, Cassidy A. Nillni, Yael I. Suvak, Michael Wiltsey-Stirman, Shannon Resick, Patricia A. TI Longitudinal course of anxiety sensitivity and PTSD symptoms in cognitive-behavioral therapies for PTSD SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Anxiety sensitivity; Posttraumatic stress disorder; Treatment; Cognitive therapy ID POSTTRAUMATIC-STRESS-DISORDER; PROCESSING THERAPY; PANIC-ATTACKS; FEMALE VICTIMS; DIMENSIONS; EXPOSURE; PREVENTION; PREDICTION; CLUSTERS; VIOLENCE AB Anxiety sensitivity (AS) has been conceptualized as trait-like vulnerability and maintenance factor for PTSD. Although recent literature has demonstrated its malleability during treatment, few have examined its influence on and effect from PTSD treatment. Using multilevel regression analyses we examined: (a) changes in AS during treatment and (b) whether pre-treatment AS predicted PTSD treatment response, in sample of female victims of interpersonal trauma receiving one of three treatments (cognitive processing therapy, cognitive processing therapy-cognitive, and written accounts). Participants exhibited reductions in total ASI scores from pre- to post-treatment. Growth curve modeling revealed slightly different trajectories of PTSD symptoms as a function of pre-treatment AS, and overall decreases in PTSD symptoms during treatment were not associated with pretreatment AS. Pretreatment AS dimensions impacted PTSD total scores and symptoms clusters differentially. Clinical and theoretical implications for these results are discussed. Published by Elsevier Ltd. C1 [Gutner, Cassidy A.; Nillni, Yael I.; Suvak, Michael; Wiltsey-Stirman, Shannon; Resick, Patricia A.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Gutner, Cassidy A.; Nillni, Yael I.; Wiltsey-Stirman, Shannon; Resick, Patricia A.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div, Boston, MA USA. [Suvak, Michael] Suffolk Univ, Dept Psychol, Boston, MA 02108 USA. RP Gutner, CA (reprint author), VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div, Boston, MA USA. EM cassidy.gutner@va.gov OI Gutner, Cassidy A./0000-0002-9406-6638; Wiltsey Stirman, Shannon/0000-0001-9917-5078 FU NIMH NIH HHS [R01 MH051509, T32 MH019836, T32MH019836-15A2, 1 R01-MH51509] NR 41 TC 3 Z9 3 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 EI 1873-7897 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD OCT PY 2013 VL 27 IS 7 BP 728 EP 734 DI 10.1016/j.janxdis.2013.09.010 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 261ST UT WOS:000327685600014 PM 24176804 ER PT J AU MacDonald, DE Rapuano, BE Vyas, P Lane, JM Meyers, K Wright, T AF MacDonald, Daniel E. Rapuano, Bruce E. Vyas, Parth Lane, Joseph M. Meyers, Kathleen Wright, Timothy TI Heat and Radiofrequency Plasma Glow Discharge Pretreatment of a Titanium Alloy Promote Bone Formation and Osseointegration SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE DENTAL IMPLANT; FIBRONECTIN; OSTEOBLAST; CELL DIFFERENTIATION; BONE MINERALIZATION; OSSEOINTEGRATION ID OXIDE NET CHARGE; OSTEOBLAST ADHESION; DENTAL IMPLANTS; CELL-ADHESION; SURFACE; FIBRONECTIN; TOPOGRAPHY; SITES; DIFFERENTIATION; INTEGRATION AB Orthopedic and dental implants manifest increased failure rates when inserted into low density bone. We determined whether chemical pretreatments of a titanium alloy implant material stimulated new bone formation to increase osseointegration in vivo in trabecular bone using a rat model. Titanium alloy rods were untreated or pretreated with heat (600 degrees C) or radiofrequency plasma glow discharge (RFGD). The rods were then coated with the extracellular matrix protein fibronectin (1nM) or left uncoated and surgically implanted into the rat femoral medullary cavity. Animals were euthanized 3 or 6 weeks later, and femurs were removed for analysis. The number of trabeculae in contact with the implant surface, surface contact between trabeculae and the implant, and the length and area of bone attached to the implant were measured by histomorphometry. Implant shear strength was measured by a pull-out test. Both pretreatments and fibronectin enhanced the number of trabeculae bonding with the implant and trabeculae-to-implant surface contact, with greater effects of fibronectin observed with pretreated compared to untreated implants. RFGD pretreatment modestly increased implant shear strength, which was highly correlated (r(2)=0.87-0.99) with measures of trabecular bonding for untreated and RFGD-pretreated implants. In contrast, heat pretreatment increased shear strength 3-5-fold for both uncoated and fibronectin-coated implants at 3 and 6 weeks, suggesting a more rapid increase in implant-femur bonding compared to the other groups. In summary, our findings suggest that the heat and RFGD pretreatments can promote the osseointegration of a titanium alloy implant material. J. Cell. Biochem. 114: 2363-2374, 2013. (c) 2013 Wiley Periodicals, Inc. C1 [MacDonald, Daniel E.; Rapuano, Bruce E.; Vyas, Parth; Lane, Joseph M.; Meyers, Kathleen; Wright, Timothy] Cornell Univ, Weill Med Coll, Hosp Special Surg, New York, NY 10021 USA. [MacDonald, Daniel E.] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [MacDonald, Daniel E.] Columbia Univ, Langmuir Ctr Colloids & Interfaces, New York, NY 10027 USA. RP MacDonald, DE (reprint author), Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA. EM dem14@columbia.edu FU National Center for Research Resources, NIH [C06-RR12538-01] FX The sponsor did not have any role in the study design; the collection, analysis and interpretation of data; the writing of the report; or the decision to submit the article for publication. This material also resulted from work supported with resources and the use of facilities at the James J. Peters VA Medical Center, Bronx, New York. This investigation was also conducted at the HSS research facility constructed with support of Grant C06-RR12538-01 from the National Center for Research Resources, NIH. We thank Dr. Hannes Schniepp for the AFM surface analyses, Dr. Stephen Doty, and Tony Labissiere for technical assistance with the SEM analyses, Dr. Adele Boskey and Lyudmila Spevak for assistance with FTIR, and Kyle Hackshaw, Carrie Guan, and Jenny Lee for help with preparation of the alloy implants. NR 50 TC 4 Z9 4 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-2312 EI 1097-4644 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD OCT PY 2013 VL 114 IS 10 BP 2363 EP 2374 DI 10.1002/jcb.24585 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 263NP UT WOS:000327815600017 PM 23649564 ER PT J AU Kacmarek, RM Villar, J AF Kacmarek, R. M. Villar, J. TI Management of refractory hypoxemia in ARDS SO MINERVA ANESTESIOLOGICA LA English DT Article DE Respiratory distress syndrome, adult; Respiration, artificial; Patient positioning ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; ACUTE LUNG INJURY; RANDOMIZED CONTROLLED-TRIAL; INHALED NITRIC-OXIDE; EXTRACORPOREAL MEMBRANE-OXYGENATION; FREQUENCY OSCILLATORY VENTILATION; SEVERE PULMONARY-HYPERTENSION; 2009 INFLUENZA A(H1N1); RECRUITMENT MANEUVERS AB Severe hypoxemia is the hallmark of ARDS. However, unmanageable refractory hypoxemia fortunately is a rare occurrence in patients with ARDS and an infrequent cause of death in ARDS. However, in some patients, in spite of the application of lung protective ventilation with moderate to high levels of end-expiratory pressure (PEEP), refractory hypoxemia remains unresolved. When refractory hypoxemia persists, we first recommend the use of lung recruitment maneuvers and a decremental PEEP trial, if this does not resolve the refractory hypoxemia prone positioning should be attempted. The use of aerosolized pulmonary vasodilators can be used to buy time when these approaches fail as the patient is transitioned to extracorporeal membrane oxygenation. We also find that there is now sufficient evidence to recommend against the use of high frequency oscillation in the management of refractory hypoxemia. C1 [Kacmarek, R. M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Kacmarek, R. M.] Harvard Univ, Dept Anesthesia, Boston, MA 02115 USA. [Villar, J.] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, J.] Hosp Univ Dr Negrin, Res Unit, Las Palmas Gran Canaria, Spain. [Villar, J.] St Michaels Hosp, Keenan Res Ctr, Toronto, ON M5B 1W8, Canada. [Villar, J.] St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. EM rkacmarek@partners.org FU Instituto de Salud Carlos III, Spain [PI10/0393] FX The present study was supported in part by and Instituto de Salud Carlos III, Spain (PI10/0393). NR 43 TC 11 Z9 13 U1 0 U2 6 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0375-9393 EI 1827-1596 J9 MINERVA ANESTESIOL JI Minerva Anestesiol. PD OCT PY 2013 VL 79 IS 10 BP 1173 EP 1179 PG 7 WC Anesthesiology; Critical Care Medicine SC Anesthesiology; General & Internal Medicine GA 263KS UT WOS:000327808100013 PM 23857446 ER PT J AU Boissel, L Betancur-Boissel, M Lu, WQ Krause, DS Van Etten, RA Wels, WS Klingemann, H AF Boissel, Laurent Betancur-Boissel, Monica Lu, Weiquan Krause, Daniela S. Van Etten, Richard A. Wels, Winfried S. Klingemann, Hans TI Retargeting NK-92 cells by means of CD19-and CD20-specific chimeric antigen receptors compares favorably with antibody-dependent cellular cytotoxicity SO ONCOIMMUNOLOGY LA English DT Article DE CAR; lentiviral vector; lymphoid malignancies; NK cells; NK-92 ID NATURAL-KILLER-CELLS; EX-VIVO EXPANSION; LINE NK-92; NK CELLS; STEM-CELLS; CANCER; LYMPHOMA; IMMUNOTHERAPY; LEUKEMIA; DIFFERENTIATION AB Multiple natural killer (NK) cell-based anticancer therapies are currently under development. Here, we compare the efficiency of genetically modified NK-92 cells expressing chimeric antigen receptors (CARs) at killing NK cell-resistant B-lymphoid leukemia cells to the antibody-dependent cell-mediated cytotoxicity (ADCC) of NK-92 cells expressing a high affinity variant of the IgG Fc receptor (FcRIII). First, we compared in vitro the abilities of NK-92 cells expressing CD20-targeting CARs to kill primary chronic lymphocytic leukemia (CLL) cells derived from 9 patients with active, untreated disease to the cytotoxicity of NK-92 cells expressing FcRIII combined with either of the anti-CD20 monoclonal antibodies (mAbs) rituximab or ofatumumab. We found that CAR-expressing NK-92 cells effectively kill NK cell-resistant primary CLL cells and that such a cytotoxic response is significantly stronger than that resulting from ADCC. For studying CAR-expressing NK cell-based immunotherapy in vivo, we established xenograft mouse models of residual leukemia using the human BCR-ABL1(+) cell lines SUP-B15 (CD19(+)CD20(-)) and TMD-5 (CD19(+)CD20(+)), two acute lymphoblastic leukemia (ALL) lines that are resistant to parental NK-92 cells. Intravenous injection of NK-92 cells expressing CD19-targeting CARs eliminated SUP-B15 cells, whereas they had no such effect on TMD-5 cells. However, the intrafemoral injection of NK-92 cells expressing CD19-targeting CAR resulted in the depletion of TMD-5 cells from the bone marrow environment. Comparative studies in which NK-92 cells expressing either CD19- or CD20-targeting CARs were directly injected into subcutaneous CD19(+)CD20(+) Daudi lymphoma xenografts revealed that CD20-targeting CAR is superior to its CD19-specific counterpart in controlling local tumor growth. In summary, we show here that CAR-expressing NK-92 cells can be functionally superior to ADCC (as mediated by anti-CD20 mAbs) in the elimination of primary CLL cells. Moreover, we provide data demonstrating that the systemic administration of CAR-expressing NK-92 cells can control lymphoblastic leukemia in immunocompromised mice. Our results also suggest that the direct injection of CAR-expressing NK-92 cells to neoplastic lesions could be an effective treatment modality against lymphoma. C1 [Boissel, Laurent; Betancur-Boissel, Monica; Lu, Weiquan; Van Etten, Richard A.; Klingemann, Hans] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA USA. [Lu, Weiquan; Van Etten, Richard A.; Klingemann, Hans] Tufts Med Ctr, Div Hematol Oncol, Boston, MA USA. [Krause, Daniela S.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Krause, Daniela S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Wels, Winfried S.] Chemotherapeut Forschungsinst Georg Speyer Haus, Frankfurt, Germany. RP Klingemann, H (reprint author), Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA USA. EM hans.klingemann@tufts.edu FU National Institutes of Health [R01 CA090576, R01 HL093981, K08 CA138916] FX The authors thank the staff at Flow Cytometry and Small Animal Services Core Facilities of the Tufts Medical Center Cancer Center for assistance. This work was supported by grants from the National Institutes of Health (R01 CA090576 to R. A. V., R01 HL093981 to H. K. and R. A. V., and K08 CA138916 to D.S.K.) NR 33 TC 39 Z9 42 U1 1 U2 10 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 EI 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD OCT 1 PY 2013 VL 2 IS 10 AR e26527 DI 10.4161/onci.26527 PG 8 WC Oncology; Immunology SC Oncology; Immunology GA 262LO UT WOS:000327737000002 PM 24404423 ER PT J AU Cooper, ZA Frederick, DT Juneja, VR Sullivan, RJ Lawrence, DP Piris, A Sharpe, AH Fisher, DE Flaherty, KT Wargo, JA AF Cooper, Zachary A. Frederick, Dennie T. Juneja, Vikram R. Sullivan, Ryan J. Lawrence, Donald P. Piris, Adriano Sharpe, Arlene H. Fisher, David E. Flaherty, Keith T. Wargo, Jennifer A. TI BRAF inhibition is associated with increased clonality in tumor-infiltrating lymphocytes SO ONCOIMMUNOLOGY LA English DT Article DE BRAF; T cells; TILs; melanoma; vemurafenib ID RAF INHIBITION; METASTATIC MELANOMA; ACQUIRED-RESISTANCE; MUTATIONS; MEK; BRAF(V600E); VEMURAFENIB; CANCER; MICROENVIRONMENT; RECOGNITION AB There have been significant advances with regard to BRAF-targeted therapies against metastatic melanoma. However, the majority of patients receiving BRAF inhibitors (BRAFi) manifest disease progression within a year. We have recently shown that melanoma patients treated with BRAFi exhibit an increase in melanoma-associated antigens and in CD8+ tumor-infiltrating lymphocytes in response to therapy. To characterize such a T-cell infiltrate, we analyzed the complementarity-determining region 3 (CDR3) of rearranged T-cell receptor (TCR) chain-coding genes in tumor biopsies obtained before the initiation of BRAFi and 10-14 d later. We observed an increase in the clonality of tumor-infiltrating lymphocytes in 7 of 8 patients receiving BRAFi, with a statistically significant 21% aggregate increase in clonality. Over 80% of individual T-cell clones detected after initiation of BRAFi treatment were new clones. Interestingly, the comparison of tumor infiltrates with clinical responses revealed that patients who had a high proportion of pre-existing dominant clones after the administration of BRAFi responded better to therapy than patients who had a low proportion of such pre-existing dominant clones following BRAFi. These data suggest that although the inhibition of BRAF in melanoma patients results in tumor infiltration by new lymphocytes, the response to treatment appears to be related to the presence of a pre-existing population of tumor-infiltrating T-cell clones. C1 [Cooper, Zachary A.; Wargo, Jennifer A.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Cooper, Zachary A.; Wargo, Jennifer A.] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. [Frederick, Dennie T.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Juneja, Vikram R.; Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA USA. [Juneja, Vikram R.] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Sullivan, Ryan J.; Lawrence, Donald P.; Flaherty, Keith T.] Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. [Sullivan, Ryan J.; Lawrence, Donald P.; Piris, Adriano; Fisher, David E.; Flaherty, Keith T.] Harvard Univ, Sch Med, Boston, MA USA. [Piris, Adriano] Massachusetts Gen Hosp, Div Dermatopathol, Boston, MA 02114 USA. [Fisher, David E.] Massachusetts Gen Hosp, Div Dermatol, Boston, MA 02114 USA. RP Wargo, JA (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. EM jwargo@mdanderson.org OI Cooper, Zachary/0000-0003-1059-0940 FU NCI NIH HHS [P01 CA163222]; NIAMS NIH HHS [R01 AR043369] NR 32 TC 38 Z9 39 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 EI 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD OCT 1 PY 2013 VL 2 IS 10 AR UNSP e26615 DI 10.4161/onci.26615 PG 7 WC Oncology; Immunology SC Oncology; Immunology GA 262LO UT WOS:000327737000028 PM 24251082 ER PT J AU Duraiswamy, J Freeman, G Coukos, G AF Duraiswamy, Jaikumar Freeman, Gordon Coukos, George TI Replenish the source within Rescuing tumor-infiltrating lymphocytes by double checkpoint blockade SO ONCOIMMUNOLOGY LA English DT Editorial Material DE CTLA4; PD-1; regulatory T cells; tumor-infiltrating lymphocytes; vaccine ID T-CELLS; OVARIAN-CANCER; REGULATORY T; MELANOMA; PD-1 AB We have recently reported that the PD-1 and CTLA4 signaling pathways are active in both effector and regulatory T cells, causing profound immune dysfunctions in the tumor microenvironment. In line with this notion, the dual blockade of PD-1- and CTLA4-conveyed signals may exert robust therapeutic effects. Here, we discuss the mechanisms possibly underlying such a synergic interaction. C1 [Duraiswamy, Jaikumar; Coukos, George] Univ Penn, Perelman Sch Med, Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA. [Freeman, Gordon] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Coukos, George] Univ Lausanne Hosp, Dept Oncol, Lausanne, Switzerland. [Coukos, George] Univ Lausanne Hosp, Ludwig Ctr Canc Res, Lausanne, Switzerland. RP Coukos, G (reprint author), Univ Penn, Perelman Sch Med, Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA. EM gcks@mail.med.upenn.edu FU NCI NIH HHS [P50 CA083638]; NIAID NIH HHS [P01 AI056299] NR 10 TC 4 Z9 4 U1 1 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 EI 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD OCT 1 PY 2013 VL 2 IS 10 AR e25912 DI 10.4161/onci.25912 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA 262LO UT WOS:000327737000012 PM 24404420 ER PT J AU Lin, DT Lin, AC AF Lin, Derrick T. Lin, Alice C. TI Surgical Treatment of Traumatic Injuries of the Cranial Base SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Skull base trauma; Craniofacial trauma; Skull base fractures; Basilar skull fractures; Surgical treatment of skull fractures; CSF leak ID CEREBROSPINAL-FLUID RHINORRHEA; ANTIBIOTIC-PROPHYLAXIS; ENDOSCOPIC REPAIR; MANAGEMENT; FRACTURES; FISTULAS; LEAKS; DIAGNOSIS; EXPERIENCE AB Skull-base fractures involve one or more of the bones that constitute the cranial base; the cribriform plate. the orbital plate of the frontal bone, sphenoid bone, occipital bone, and petrous or temporal bone. Although the fractures only require reduction and reconstruction when the skull base is severely comminuted or altered, even small fractures are associated with traumatic shear forces which create tears in the meninges and thus predispose to cerebrospinal fluid leaks. This article explores the preoperative, intraoperative, and postoperative management of skull-base fractures, which most commonly involves resolution of the cerebrospinal fluid leak and the prevention of future leaks or meningoencephaloceles. C1 [Lin, Derrick T.; Lin, Alice C.] Harvard Univ, Massachusetts Eye & Ear Infirm, Massachusetts Gen Hosp, Div Head & Neck Oncol,Med Sch, Boston, MA 02114 USA. RP Lin, DT (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Massachusetts Gen Hosp, Div Head & Neck Oncol,Med Sch, 243 Charles St, Boston, MA 02114 USA. EM Derrick_Lin@meei.harvard.edu NR 34 TC 3 Z9 5 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0030-6665 EI 1557-8259 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD OCT PY 2013 VL 46 IS 5 BP 749 EP + DI 10.1016/j.otc.2013.06.008 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA 264UB UT WOS:000327905400004 PM 24138735 ER PT J AU Garrido, MM Idler, EL Leventhal, H Carr, D AF Garrido, Melissa M. Idler, Ellen L. Leventhal, Howard Carr, Deborah TI Pathways From Religion to Advance Care Planning: Beliefs About Control Over Length of Life and End-of-Life Values SO GERONTOLOGIST LA English DT Article DE Advance directive; living wills; durable power of attorney for healthcare ID TREATMENT PREFERENCES; DECISION-MAKING; RACIAL-DIFFERENCES; CANCER-PATIENTS; DIRECTIVES; HEALTH; DEATH; PHYSICIANS; RESIDENTS; ATTITUDES AB Purpose of the Study: To evaluate the extent to which religious affiliation and self-identified religious importance affect advance care planning (ACP) via beliefs about control over life length and end-of-life values. Design and Methods: Three hundred and five adults aged 55 and older from diverse racial and socioeconomic groups seeking outpatient care in New Jersey were surveyed. Measures included discussion of end-of-life preferences; living will (LW) completion; durable power of attorney for healthcare (DPAHC) appointment; religious affiliation; importance of religion; and beliefs about who/what controls life length, end-of-life values, health status, and sociodemographics. Results: Of the sample, 68.9% had an informal discussion and 46.2% both discussed their preferences and did formal ACP (LW and/or DPAHC). Conservative Protestants and those placing great importance on religion/spirituality had a lower likelihood of ACP. These associations were largely accounted for by beliefs about God's controlling life length and values for using all available treatments. Implications: Beliefs and values about control account for relationships between religiosity and ACP. Beliefs and some values differ by religious affiliation. As such, congregations may be one nonclinical setting in which ACP discussions could be held, as individuals with similar attitudes toward the end of life could discuss their treatment preferences with those who share their views. C1 [Garrido, Melissa M.] GRECC, James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Garrido, Melissa M.] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY USA. [Idler, Ellen L.] Emory Univ, Dept Sociol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Idler, Ellen L.] Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Leventhal, Howard] Rutgers State Univ, Dept Psychol, New Brunswick, NJ 08903 USA. [Leventhal, Howard] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, New Brunswick, NJ 08903 USA. [Carr, Deborah] Rutgers State Univ, Dept Sociol, New Brunswick, NJ 08903 USA. [Carr, Deborah] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, New Brunswick, NJ 08903 USA. RP Garrido, MM (reprint author), GRECC, James J Peters VA Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM melissa.garrido@mssm.edu FU NIA NIH HHS [AG023958]; NIMH NIH HHS [T32 MH16242-29] NR 38 TC 11 Z9 11 U1 4 U2 22 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2013 VL 53 IS 5 BP 801 EP 816 DI 10.1093/geront/gns128 PG 16 WC Gerontology SC Geriatrics & Gerontology GA 258DL UT WOS:000327439300010 PM 23161430 ER PT J AU Bradley, KA Chavez, LJ Lapham, GT Williams, EC Achtmeyer, CE Rubinsky, AD Hawkins, EJ Saitz, R Kivlahan, DR AF Bradley, Katharine A. Chavez, Laura J. Lapham, Gwendolyn T. Williams, Emily C. Achtmeyer, Carol E. Rubinsky, Anna D. Hawkins, Eric J. Saitz, Richard Kivlahan, Daniel R. TI When Quality Indicators Undermine Quality: Bias in a Quality Indicator of Follow-Up for Alcohol Misuse SO PSYCHIATRIC SERVICES LA English DT Article ID SERVICES-TASK-FORCE; PRIMARY-CARE; HEALTH-CARE; PREVENTIVE-SERVICES; MENTAL-HEALTH; PERFORMANCE-MEASURES; MEANINGFUL USE; INTERVENTIONS; ACCOUNTABILITY; IMPROVEMENT AB Objective: Valid quality indicators are needed to monitor and encourage identification and management of mental health and substance use conditions (behavioral conditions). Because behavioral conditions are frequently underidentified, quality indicators often evaluate the proportion of patients who screen positive for a condition who also have appropriate follow-up care documented. However, these "positive-screen-based" quality indicators of follow-up for behavioral conditions could be biased by differences in the denominator due to differential screening quality ("denominator bias") and could reward identification of fewer patients with the behavioral conditions of interest. This study evaluated denominator bias in the performance of Veterans Health Administration (VHA) networks on a quality indicator of follow-up for alcohol misuse that used the number of patients with positive alcohol screens as the denominator. Methods: Two quality indicators of follow-up for alcohol misuse-a positive-screen-based quality indicator and a population-based quality indicator-were compared among 21 VHA networks by review of 219,119 medical records. Results: Results for the two quality indicators were inconsistent. For example, two networks performed similarly on the quality indicators (64.7% and 65.4% follow-up) even though one network identified and documented follow-up for almost twice as many patients (5,411 and 2,899 per 100,000 eligible, respectively). Networks that performed better on the positive-screen-based quality indicator identified fewer patients with alcohol misuse than networks that performed better on the population-based quality indicator (mean 4.1% versus 7.4%, respectively). Conclusions: A positive-screen-based quality indicator of follow-up for alcohol misuse preferentially rewarded networks that identified fewer patients with alcohol misuse. C1 [Bradley, Katharine A.; Lapham, Gwendolyn T.] Grp Hlth Res Inst, Seattle, WA 98101 USA. [Chavez, Laura J.; Williams, Emily C.; Achtmeyer, Carol E.; Rubinsky, Anna D.; Kivlahan, Daniel R.] Vet Affairs VA Hlth Serv Res & Dev, Northwest Ctr Excellence, Seattle, WA USA. [Chavez, Laura J.; Williams, Emily C.] Univ Washington, Dept Hlth Serv, Sch Publ Hlth, Seattle, WA 98195 USA. [Hawkins, Eric J.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. [Saitz, Richard] Boston Univ, Dept Gen Internal Med, Boston, MA 02215 USA. RP Bradley, KA (reprint author), Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM bradley.k@ghc.org FU Substance Use Disorders Quality Enhancement Research Initiative from VA Health Services Research and Development [SUB98-000]; National Institute on Alcohol Abuse and Alcoholism [NIAAA R21 AA020894-01A1]; Group Health Research Institute FX This study was supported by the Substance Use Disorders Quality Enhancement Research Initiative SUB98-000 from VA Health Services Research and Development, by grant NIAAA R21 AA020894-01A1 from the National Institute on Alcohol Abuse and Alcoholism, and by the Group Health Research Institute. Funders had no role in the conduct or reporting of research. Data were provided via a data use agreement with the VA OABI (formerly the VA Office of Quality and Performance), which had no role in design or analyses but reviewed the manuscript before submission to ensure accurate use and reporting of data. NR 51 TC 9 Z9 9 U1 4 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD OCT PY 2013 VL 64 IS 10 BP 1018 EP 1025 DI 10.1176/appi.ps.201200449 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 255ZH UT WOS:000327278200022 PM 23852137 ER PT J AU Stirman, SW Calloway, A Toder, K Miller, CJ DeVito, AK Meisel, SN Xhezo, R Evans, AC Beck, AT Crits-Christoph, P AF Stirman, Shannon Wiltsey Calloway, Amber Toder, Katherine Miller, Christopher J. DeVito, Andrea K. Meisel, Samuel N. Xhezo, Regina Evans, Arthur C. Beck, Aaron T. Crits-Christoph, Paul TI Community Mental Health Provider Modifications to Cognitive Therapy: Implications for Sustainability SO PSYCHIATRIC SERVICES LA English DT Article ID PSYCHOLOGICAL TREATMENTS; BEHAVIORAL THERAPY; DISSEMINATION; SYSTEM AB Objective: This study identified modifications to an evidence-based psychosocial treatment (cognitive therapy) within a community mental health system after clinicians had received intensive training and consultation. Methods: A coding system, consisting of four types of contextual modifications, 12 types of content-related-modifications, seven levels at which modifications can occur, and a code for changes to training or evaluation processes, was applied to data from interviews with 27 clinicians who treat adult consumers within a mental health system. Results: Nine of 12 content modifications were endorsed, and four (tailoring, integration into other therapeutic approaches, loosening structure, and drift) accounted for 65% of all modifications identified. Contextual modifications were rarely endorsed by clinicians in this sample. Modifications typically occurred at the client or clinician level. Conclusions: Clinicians in community mental health settings made several modifications to an evidence-based practice (EBP), often in an effort to improve the fit of the intervention to the client's needs or to the clinician's therapeutic style. These findings have implications for implementation and sustainability of EBPs in community settings, client-level outcomes, and training and consultation. C1 [Stirman, Shannon Wiltsey] VA Boston Healthcare Syst, Vet Affairs VA Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. [Stirman, Shannon Wiltsey; DeVito, Andrea K.; Meisel, Samuel N.] Boston Univ, Dept Psychiat, Boston, MA 02130 USA. [Calloway, Amber] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. [Toder, Katherine; Beck, Aaron T.; Crits-Christoph, Paul] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Miller, Christopher J.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA 02130 USA. RP Stirman, SW (reprint author), VA Boston Healthcare Syst, Vet Affairs VA Natl Ctr PTSD, Womens Hlth Sci Div, 150 S Huntington Ave 116B3, Boston, MA 02130 USA. EM sws@bu.edu FU National Institute of Mental Health (NIMH) [R00 MH01800, R25 MH080916-01A2] FX The preparation of this report was supported through grant R00 MH01800 from the National Institute of Mental Health (NIMH). While the study was being conducted, Dr. Wiltsey Stirman was receiving training from the Implementation Research Institute at the George Warren Brown School of Social Work, Washington University in St. Louis, which is funded through NIMH award R25 MH080916-01A2 and the Department of Veterans Affairs, Health Services Research and Development Service, Quality Enhancement Research Initiative. The authors are grateful to the providers who participated in the interviews and the agencies that participated in the adult outpatient training program. J. Bryce McLaulin, M.D., and Matthew Hurford, M.D., and the program's mentors and consultants also played important roles in facilitating this research. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIMH, the National Institutes of Health, or the Department of Veterans Affairs. NR 11 TC 9 Z9 9 U1 1 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD OCT PY 2013 VL 64 IS 10 BP 1056 EP 1059 DI 10.1176/appi.ps.201200456 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 255ZH UT WOS:000327278200029 ER PT J AU Ostergaard, SD AF Ostergaard, Soren Dinesen TI The Evidence-Based Guide to Antidepressant Medications SO PSYCHIATRIC SERVICES LA English DT Book Review C1 [Ostergaard, Soren Dinesen] Aalborg Psychiat Hosp, Unit Psychiat Res, Aalborg, Denmark. [Ostergaard, Soren Dinesen] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Ostergaard, SD (reprint author), Aalborg Psychiat Hosp, Unit Psychiat Res, Aalborg, Denmark. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD OCT PY 2013 VL 64 IS 10 BP E3 EP E3 PG 1 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 255ZH UT WOS:000327278200003 ER PT J AU Gradl, G Jupiter, JB AF Gradl, G. Jupiter, J. B. TI Current Concepts Review - Fractures of the Shaft of the Humerus SO ACTA CHIRURGIAE ORTHOPAEDICAE ET TRAUMATOLOGIAE CECHOSLOVACA LA English DT Review ID SHOULDER ARTHROPLASTY; DIAPHYSEAL FRACTURES; PLATE FIXATION; COMPRESSION PLATE; FUNCTIONAL BRACE; ANTEGRADE; COMPLICATIONS; EPIDEMIOLOGY; NONUNIONS; NAIL AB Fractures of the shaft of the humerus are common injuries. Historically, the treatment of choice has been functional bracing. Recent technical advances such as angular stable plate and nail constructs lead to a shift in the treatment algorithm for this type of fracture. Surgical treatment is recommended in high grade open fractures, multilevel injury, polytrauma patients, nerve and serious vascular injuries, pathological fractures, and delayed or nonunions. This article aims to describe the published scientific data and current treatment modalities most suitable for each type of fracture. C1 [Gradl, G.] Univ Aachen, Med Ctr, Dept Trauma & Reconstruct Surg, D-52074 Aachen, Germany. [Jupiter, J. B.] Massachussetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA USA. RP Gradl, G (reprint author), Univ Aachen, Med Ctr, Dept Trauma & Reconstruct Surg, Pauwelsstr 30, D-52074 Aachen, Germany. EM ggradl@ukaachen.de NR 34 TC 0 Z9 0 U1 2 U2 9 PU GALEN SRO PI PRAGUE 5 PA NA BELIDLE 34, PRAGUE 5, 150 00, CZECH REPUBLIC SN 0001-5415 J9 ACTA CHIR ORTHOP TR JI Acta Chir. Orthop. Traumatol. Cechoslov. PD OCT PY 2013 VL 80 IS 5 BP 321 EP 327 PG 7 WC Orthopedics SC Orthopedics GA 250JH UT WOS:000326848600002 PM 25105672 ER PT J AU Hosoya, Y Ando, S Otani, H Yukinari, T Miyazaki, M Garcia-Godoy, F AF Hosoya, Yumiko Ando, Susumu Otani, Hedeji Yukinari, Tetsubiro Miyazaki, Masashi Garcia-Godoy, Franklin TI Ability of Barrier Coat S-PRG coating to arrest artificial enamel lesions in primary teeth SO AMERICAN JOURNAL OF DENTISTRY LA English DT Article ID ELASTIC-MODULUS; NANO-HARDNESS; CANINE DENTIN; FLUORIDE; FILLER; DEMINERALIZATION; REMINERALIZATION; PREVENTION; CARIES; LEVEL AB Purpose: To evaluate the effects of a surface pre-reacted glass-ionomer (S-PRO) filled coating material to arrest artificial enamel lesions in primary teeth. Methods: Buccal and lingual enamel was demineralized in 0.1 M lactic acid buffer solution (pH 4.75) for 5 days and then divided in the PRO-applied and non-PRG areas. Proximal surfaces were used as a control area without demineralization and coating application. Teeth were divided into three groups (n= 4) according to the 1-week immersion in different solutions: Group 1 (distilled water), Group 2 (demineralizing solution) and Group 3 (artificial saliva). Hardness and Young's modulus by nano-indentation test, and elemental contents and ultrastructure by SEM/EDX analysis were obtained. Data were statistically analyzed using ANOVA and Fisher's PLSD at alpha= 0.05. Results: Only for the non-PRG area in Group 1, the hardness and Young's modulus of the demineralized surface enamel were significantly lower than those of the enamel 30-60 mu m beneath the surface. Demineralized enamel of non-PRG and PRO-applied areas showed similar SEM views. Only for the non-PRO area in Group 2 and control area in Group 3, the Ca/P of the surface enamel was significantly higher than that of the enamel 5-10 mu m beneath the surface. There was no significant difference of the Ca/P among the measuring points from the surface to 10 mu m depth of enamel for the PRG applied area in Group 2. C1 [Hosoya, Yumiko] Nagasaki Univ, Grad Sch Biomed Sci, Course Med & Dent Sci, Dept Pediat Dent,Unit Translat Med, Nagasaki 8528588, Japan. [Ando, Susumu; Miyazaki, Masashi] Nihon Univ, Sch Dent, Dept Operat Dent, Tokyo 101, Japan. [Otani, Hedeji] Otani Dent Clin, Nayoro, Hokkaido, Japan. [Yukinari, Tetsubiro] Yukinari Pediat & Orthodont Dent Clin, Nagasaki, Japan. [Garcia-Godoy, Franklin] Univ Tennessee, Biosci Res Ctr, Coll Dent, Memphis, TN USA. [Garcia-Godoy, Franklin] Forsyth Ctr, Cambridge, MA USA. RP Hosoya, Y (reprint author), Nagasaki Univ, Grad Sch Biomed Sci, Course Med & Dent Sci, Dept Pediat Dent,Unit Translat Med, 1-7-1 Sakamoto, Nagasaki 8528588, Japan. EM hosoya@nagasaki-u.ac.jp NR 19 TC 1 Z9 2 U1 1 U2 4 PU MOSHER & LINDER, INC PI WESTON PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA SN 0894-8275 J9 AM J DENT JI Am. J. Dent. PD OCT PY 2013 VL 26 IS 5 BP 286 EP 290 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 251CP UT WOS:000326905700010 PM 24479282 ER PT J AU Brumpton, B Leivseth, L Romundstad, PR Langhammer, A Chen, Y Camargo, CA Mai, XM AF Brumpton, Ben Michael Leivseth, Linda Romundstad, Pal Richard Langhammer, Arnulf Chen, Yue Camargo, Carlos Arturo, Jr. Mai, Xiao-Mei TI The joint association of anxiety, depression and obesity with incident asthma in adults: the HUNT Study SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Body mass index; epidemiology; interaction; psychological distress ID MENTAL-DISORDERS; PSYCHOSOCIAL FACTORS; GENERAL-POPULATION; HOSPITAL ANXIETY; HEALTH SURVEY; COHORT; RISK; SYMPTOMS; STRESS; METAANALYSIS AB Background Anxiety or depression symptoms may increase the risk of developing asthma, and their interaction with obesity is not known. We aimed to assess the association of anxiety or depression symptoms and the joint association of these symptoms and obesity with incident asthma. Methods We conducted a prospective cohort study of 23 599 adults who were 19-55 years old and free from asthma at baseline in the Norwegian Nord-Tr circle divide ndelag Health Study. The Hospital Anxiety and Depression Scale was used to measure anxiety or depression symptoms. Obesity was defined as a body mass index epsilon 30.0 kg/m(2). Incident asthma was self-reported new cases of asthma during the 11-year follow-up. Results Having anxiety or depression symptoms was associated with incident asthma [odds ratio (OR) 1.39, 95% confidence interval (CI) 1.09-1.78). Obese participants with anxiety or depression symptoms had a substantially higher risk of incident asthma (OR 2.93, 95% CI 2.20-3.91) than any other group (non-obese participants without anxiety or depression symptoms [reference], non-obese participants with anxiety or depression symptoms (OR 1.20, 95% CI 1.00-1.45) and obese participants without anxiety or depression symptoms (OR 1.47, 95% CI 1.19-1.82)]. The relative excess risk for incident asthma due to interaction between anxiety or depression symptoms and obesity was 1.26 (95% CI 0.39-2.12). Conclusions This study suggests that having anxiety or depression symptoms contributes to the development of asthma in adults. The risk of asthma may be further increased by the interaction between anxiety or depression symptoms and obesity. C1 [Brumpton, Ben Michael; Leivseth, Linda; Romundstad, Pal Richard; Langhammer, Arnulf; Mai, Xiao-Mei] Norwegian Univ Sci & Technol, Fac Med, Dept Publ Hlth & Gen Practice, N-7034 Trondheim, Norway. [Chen, Yue] Univ Ottawa, Fac Med, Dept Epidemiol & Community Med, Ottawa, ON, Canada. [Camargo, Carlos Arturo, Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Brumpton, B (reprint author), NTNU, Fak Med, Inst Samfunnsmed, MTFS, Postboks 8905, N-7491 Trondheim, Norway. EM ben.brumpton@ntnu.no RI Osborne, Nicholas/N-4915-2015; OI Osborne, Nicholas/0000-0002-6700-2284; Romundstad, Pal Richard/0000-0003-2061-4336 FU Research Council of Norway [201895/V50]; Faculty of Medicine at the Norwegian University of Science and Technology FX This study was supported by the Research Council of Norway (project no. 201895/V50) and the Faculty of Medicine at the Norwegian University of Science and Technology. NR 48 TC 8 Z9 8 U1 2 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 EI 1464-3685 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD OCT PY 2013 VL 42 IS 5 BP 1455 EP 1463 DI 10.1093/ije/dyt151 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 248TI UT WOS:000326726000037 PM 24008330 ER PT J AU Kendler, DL Borges, JLC Fielding, RA Itabashi, A Krueger, D Mulligan, K Camargos, BM Sabowitz, B Wu, CH Yu, EW Shepherd, J AF Kendler, David L. Borges, Joao L. C. Fielding, Roger A. Itabashi, Akira Krueger, Diane Mulligan, Kathleen Camargos, Bruno M. Sabowitz, Brian Wu, Chih-Hsing Yu, Elaine W. Shepherd, John TI The Official Positions of the International Society for Clinical Densitometry: Indications of Use and Reporting of DXA for Body Composition SO JOURNAL OF CLINICAL DENSITOMETRY LA English DT Article DE Body composition; DXA; obesity; sarcopenia ID X-RAY ABSORPTIOMETRY; BONE-MINERAL DENSITY; PLACEBO-CONTROLLED TRIAL; VISCERAL ADIPOSE-TISSUE; GASTRIC BYPASS-SURGERY; HIV-INFECTED PATIENTS; OBESE OLDER-ADULTS; TRANSCRIPTASE INHIBITOR THERAPY; HORMONE-RELEASING FACTOR; PLUS DUAL NUCLEOSIDES AB The technique of body composition by dual-energy X-ray absorptiometry (DXA) has been used for several years in the research environment. Its ability to accurately, and precisely measure lean, fat, and mineral composition in various body compartments has been well validated. Furthermore, the technique is widely available to clinical patients on existing DXA instruments throughout the world through the use of specific software packages and scanning algorithms. There have been few clear statements regarding the clinical indications for body composition measurement in patients outside the research setting. This is in part because of the lack of specific documented interventions that would be affected by body composition test results, beyond usual clinical advice. We have examined a few of the most common, specific scenarios (HIV therapy, sarcopenia, bariatric surgery, obesity) and proposed indications for body composition assessment. We have also discussed contraindications to body composition testing. C1 [Kendler, David L.] Univ British Columbia, Vancouver, BC V5Z 4E1, Canada. [Borges, Joao L. C.] Univ Catolica Brasilia, Brasilia, DF, Brazil. [Fielding, Roger A.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Exercise Physiol & Sarcopenia Lab, Boston, MA 02111 USA. [Krueger, Diane] Univ Wisconsin, Madison, WI USA. [Mulligan, Kathleen; Shepherd, John] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Camargos, Bruno M.] Hosp Mater Dei, Belo Horizonte, MG, Brazil. [Wu, Chih-Hsing] Natl Cheng Kung Univ Hosp, Dept Family Med, Tainan 70428, Taiwan. [Yu, Elaine W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Kendler, DL (reprint author), Univ British Columbia, 150-943 W Broadway, Vancouver, BC V5Z 4E1, Canada. EM davidkendler@gmail.com OI Camargos, Bruno/0000-0002-3132-6455; Kendler, David/0000-0001-7679-3965 FU US Department of Agriculture [58-1950-0-014] FX The contribution by RAF is partially supported by the US Department of Agriculture under agreement no. 58-1950-0-014. Any opinions, findings, conclusion, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the US Department of Agriculture. NR 139 TC 18 Z9 18 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1094-6950 EI 1559-0747 J9 J CLIN DENSITOM JI J. Clin. Densitom. PD OCT-DEC PY 2013 VL 16 IS 4 BP 496 EP 507 DI 10.1016/j.jocd.2013.08.020 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 250KK UT WOS:000326851500019 PM 24090645 ER PT J AU Petak, S Barbu, CG Yu, EW Fielding, R Mulligan, K Sabowitz, B Wu, CH Shepherd, JA AF Petak, Steven Barbu, Carmen G. Yu, Elaine W. Fielding, Roger Mulligan, Kathleen Sabowitz, Brian Wu, Chih-Hsing Shepherd, John A. TI The Official Positions of the International Society for Clinical Densitometry: Body Composition Analysis Reporting SO JOURNAL OF CLINICAL DENSITOMETRY LA English DT Article DE Adipose mass; body composition; bone mineral density; lean mass; whole body ID ENERGY X-RAY; CARDIOVASCULAR RISK-FACTORS; SKELETAL-MUSCLE MASS; FAT-FREE MASS; ADIPOSE-TISSUE; LEAN MASS; VISCERAL FAT; ALTERNATIVE DEFINITIONS; CARDIOMETABOLIC RISK; WAIST CIRCUMFERENCE AB Dual-energy x-ray absorptiometry (DXA) measurements of body composition increasingly are used in the evaluation of clinical disorders, but there has been little guidance on how to effectively report these measures. Uniformity in reporting of body composition measures will aid in the diagnosis of clinical disorders such as obesity, sarcopenia, and lipodystrophy. At the 2013 International Society for Clinical Densitometry Position Development Conference on body composition, the reporting section recommended that all DXA body composition reports should contain parameters of body mass index, bone mineral density, BMC, total mass, total lean mass, total fat mass, and percent fat mass The inclusion of additional measures of adiposity and lean mass are optional, including visceral adipose tissue, appendicular lean mass index, android/gynoid percent fat ratio, trunk to leg fat mass ratio, lean mass index, and fat mass index. Within the United States, we recommend the use of the National Health and Nutrition Examination Survey 1999-2004 body composition dataset as an age-, gender-, and race-specific reference and to calibrate BMC in 4-compartment models. Z-scores and percentiles of body composition measures may be useful for clinical interpretation if methods are used to adjust for non-normality. In particular, DXA body composition measures may be useful for risk-stratification of obese and sarcopenia patients, but there needs to be validation of thresholds to define obesity and sarcopenia. To summarize, these guidelines provide evidence-based standards for the reporting and clinical application of DXA-based measures of body, composition. C1 [Petak, Steven] Houston Methodist Hosp, Dept Med, Houston, TX 77030 USA. [Barbu, Carmen G.] Carol Davila Univ, Elias Hosp, Dept Endocrinol, Bucharest, Romania. [Yu, Elaine W.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Fielding, Roger] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Exercise Physiol & Sarcopenia Lab, Boston, MA 02111 USA. [Mulligan, Kathleen; Shepherd, John A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Sabowitz, Brian] Univ Texas Hlth Sci Ctr San Antonio, Dept Endocrinol Diabet & Metab, San Antonio, TX 78229 USA. [Wu, Chih-Hsing] Natl Cheng Kung Univ Hosp, Dept Family Med, Tainan 70428, Taiwan. RP Petak, S (reprint author), Houston Methodist Hosp, Dept Med, Smith Tower Suite 1001, Houston, TX 77030 USA. EM spetak@petak.com FU US Department of Agriculture [58-1950-0-014] FX RF was supported by the US Department of Agriculture, agreement No. 58-1950-0-014. Any opinions, findings, conclusion, or recommendations expressed in this publication are those of the author and do not necessarily reflect the view of the US Department of Agriculture. We appreciate the comments received from representatives of instrument manufacturers, including Kevin Wilson, Tom Kelly, Tom Sanchez, and David Ergun. NR 91 TC 23 Z9 23 U1 3 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1094-6950 EI 1559-0747 J9 J CLIN DENSITOM JI J. Clin. Densitom. PD OCT-DEC PY 2013 VL 16 IS 4 BP 508 EP 519 DI 10.1016/j.jocd.2013.08.018 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 250KK UT WOS:000326851500020 PM 24183640 ER PT J AU Chapman, S Dobrovolskai, M Farahani, K Goodwin, A Joshi, A Lee, H Meade, T Pomper, M Ptak, K Rao, JH Singh, R Sridhar, S Stern, S Wang, A Weaver, JB Woloschak, G Yang, L AF Chapman, Sandra Dobrovolskai, Marina Farahani, Keyvan Goodwin, Andrew Joshi, Amit Lee, Hakho Meade, Thomas Pomper, Martin Ptak, Krzysztof Rao, Jianghong Singh, Ravi Sridhar, Srinivas Stern, Stephan Wang, Andrew Weaver, John B. Woloschak, Gayle Yang, Lily TI Nanoparticles for cancer imaging: The good, the bad, and the promise SO NANO TODAY LA English DT Article DE Nanonnedicine; Cancer; Imaging; Detection; Screening ID PARTICLES; CLEARANCE; MOLECULES AB Recent advances in molecular imaging and nanotechnology are providing new opportunities for biomedical imaging with great promise for the development of novel imaging agents. The unique optical, magnetic, and chemical properties of materials at the scale of nanometers allow the creation of imaging probes with better contrast enhancement, increased sensitivity, controlled biodistribution, better spatial and temporal information, multi-functionality and multi-modal imaging across MRI, PET, SPECT, and ultrasound. These features could ultimately translate to clinical advantages such as earlier detection, real time assessment of disease progression and personalized medicine. However, several years of investigation into the application of these materials to cancer research has revealed challenges that have delayed the successful application of these agents to the field of biomedical imaging. Understanding these challenges is critical to take full advantage of the benefits offered by nano-sized imaging agents. Therefore, this article presents the lessons learned and challenges encountered by a group of leading researchers in this field, and suggests ways forward to develop nanoparticle probes for cancer imaging. Published by Elsevier Ltd. C1 [Chapman, Sandra] NCI, Off Canc Nanotechnol Res, Ctr Strateg Sci Initiat, NIH, Bethesda, MD 20892 USA. [Dobrovolskai, Marina; Stern, Stephan] SAIC Frederick Inc, Nanotechnol Characterizat Lab, Adv Technol Res Facil, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Farahani, Keyvan] NCI, Image Guided Intervent Branch, Canc Imaging Program, Rockville, MD 20852 USA. [Goodwin, Andrew] Univ Colorado Boulder, Dept Chem & Biol Engn, Boulder, CO 80303 USA. [Joshi, Amit] Baylor Coll Med, Dept Radiol, TBMM Grad Program, Houston, TX 77030 USA. [Joshi, Amit] Baylor Coll Med, Dept Mol Physiol & Biophys, TBMM Grad Program, Houston, TX 77030 USA. [Lee, Hakho] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Meade, Thomas] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA. [Meade, Thomas] Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA. [Meade, Thomas] Northwestern Univ, Dept Radiol, Evanston, IL 60208 USA. [Pomper, Martin] Johns Hopkins Med Sch, Baltimore, MD 21287 USA. [Ptak, Krzysztof] NCI, Off Canc Ctr, Off Director, NIH, Bethesda, MD 20892 USA. [Rao, Jianghong] Stanford Univ, Mol Imaging Program Stanford, Dept Radiol, Stanford, CA 94305 USA. [Singh, Ravi] Wake Forest Sch Med, Dept Canc Biol, Winston Salem, NC 27157 USA. [Sridhar, Srinivas] Northeastern Univ, Nanomedicine Sci & Technol Ctr, Boston, MA 02115 USA. [Sridhar, Srinivas] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Wang, Andrew] Univ N Carolina, Dept Radiat Oncol, Carolina Ctr Nanotechnol Excellence, Chapel Hill, NC 27599 USA. [Weaver, John B.] Dartmouth Coll, Geisel Sch Med, Dept Radiol, Hanover, NH 03755 USA. [Woloschak, Gayle] Northwestern Univ, Dept Radiat Oncol, Robert E Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Woloschak, Gayle] Northwestern Univ, Dept Radiol, Robert E Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Woloschak, Gayle] Northwestern Univ, Dept Cell & Mol Biol, Robert E Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Yang, Lily] Emory Univ Sch Med, Dept Surg, Atlanta, GA 30322 USA. RP Chapman, S (reprint author), NCI, Off Canc Nanotechnol Res, Ctr Strateg Sci Initiat, NIH, Bethesda, MD 20892 USA. EM chapmansandra.e@gmail.com; jrao@stanford.edu; s.sridhar@neu.edu; g-woloschak@northwestern.edu RI Chapman, Sandra/I-8889-2014; Nanotechnology Characterization Lab, NCL/K-8454-2012; Singh, Ravi/A-5740-2011; Woloschak, Gayle/A-3799-2017; OI Chapman, Sandra/0000-0002-9202-336X; Singh, Ravi/0000-0003-0750-1804; Woloschak, Gayle/0000-0001-9209-8954; Wang, Andrew/0000-0002-9781-4494 FU CCR NIH HHS [HHSN261200800001C]; NCI NIH HHS [R01 CA178748, HHSN261200800001E, R00 CA154006] NR 16 TC 37 Z9 37 U1 6 U2 70 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1748-0132 EI 1878-044X J9 NANO TODAY JI Nano Today PD OCT PY 2013 VL 8 IS 5 BP 454 EP 460 DI 10.1016/j.nantod.2013.06.001 PG 7 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 252HK UT WOS:000326995500005 PM 25419228 ER PT J AU Benacerraf, B AF Benacerraf, Beryl TI The use of obstetrical ultrasound in the obese gravida SO SEMINARS IN PERINATOLOGY LA English DT Review DE Ultrasound; Obesity; Fetal anomalies; Ultrasound technique ID MATERNAL OBESITY; OVERWEIGHT; VISUALIZATION; SONOGRAPHY; WOMEN AB Obesity is an epidemic in the United States, especially among the pregnant population. Obesity is responsible for an increase in fetal anomalies and adverse outcome of both mother and fetus. Due to difficulty in penetrating to the depth of the uterus, the ultrasound image in obese patients is inadequate, fuzzy, and high in artifacts. Hence, obese patients often require multiple scans as well as special scanning techniques just to get borderline image quality. These techniques and the data regarding quality and frequency of scans for the obese pregnant population are discussed in this paper. (C) 2013 Elsevier Inc. All rights reserved. C1 [Benacerraf, Beryl] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Benacerraf, Beryl] Brigham & Womens Hosp, Dept OB GYN, Boston, MA 02115 USA. [Benacerraf, Beryl] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept OBGYN, Boston, MA USA. RP Benacerraf, B (reprint author), 1 Brookline Pl, Brookline, MA 02445 USA. EM bbsono@aol.com NR 11 TC 5 Z9 5 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0146-0005 EI 1558-075X J9 SEMIN PERINATOL JI Semin. Perinatol. PD OCT PY 2013 VL 37 IS 5 BP 345 EP 347 DI 10.1053/j.semperi.2013.06.012 PG 3 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 251FG UT WOS:000326912600013 PM 24176158 ER PT J AU Mananga, ES AF Mananga, Eugene Stephane TI Applications of Floquet-Magnus expansion, average Hamiltonian theory and Fer expansion to study interactions in solid state NMR when irradiated with the magic-echo sequence SO SOLID STATE NUCLEAR MAGNETIC RESONANCE LA English DT Article DE Solid-state NMR; Floquet-Magnus expansion; Fer expansion; Average Hamiltonian theory; Magic-echo sequence; NMR interactions ID QUADRUPOLAR NUCLEI; SAMPLE ROTATION; SPIN SYSTEMS; SPECTROSCOPY; RESONANCE; SIMULATION; DYNAMICS; I=1 AB This work presents the possibility of applying the Floquet-Magnus expansion and the For expansion approaches to the most useful interactions known in solid-state nuclear magnetic resonance using the magic-echo scheme. The results of the effective Hamiltonians of these theories and average Hamiltonian theory are presented. (C) 2013 Elsevier Inc. All rights reserved. C1 [Mananga, Eugene Stephane] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Mananga, Eugene Stephane] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging Phys, Dept Radiol, Boston, MA 02114 USA. RP Mananga, ES (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM emananga@pet.mgh.harvard.edu FU National Institute of Health (NIH) [R01-HL110241, T32 EB013180] FX E.S. Mananga acknowledges assistance from Harvard University, Harvard Medical School, Massachusetts General Hospital, and the National Institute of Health (NIH), under Grants R01-HL110241 and T32 EB013180. The contents of this paper are solely the responsibility of the author and do not represent the official views of NIH. NR 43 TC 8 Z9 8 U1 0 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0926-2040 EI 1527-3326 J9 SOLID STATE NUCL MAG JI Solid State Nucl. Magn. Reson. PD OCT-NOV PY 2013 VL 55-56 BP 54 EP 62 DI 10.1016/j.ssnmr.2013.08.002 PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical; Physics, Condensed Matter; Spectroscopy SC Chemistry; Physics; Spectroscopy GA 254AQ UT WOS:000327132700006 PM 24034855 ER PT J AU Mananga, ES AF Mananga, Eugene Stephane TI Criteria to average out the chemical shift anisotropy in solid-state NMR when irradiated with BABA I, BABA II, and C7 radiofrequency pulse sequences SO SOLID STATE NUCLEAR MAGNETIC RESONANCE LA English DT Article DE Solid-state NMR; Floquet-Magnus expansion; CSA; BABA pulse sequence; C7 pulse sequence ID ANGLE-SPINNING NMR; NUCLEAR-MAGNETIC-RESONANCE; ROTATING SOLIDS; QUANTUM NMR; DISTANCE MEASUREMENTS; SPECTROSCOPY; SIMULATION AB Floquet-Magnus expansion is used to study the effect of chemical shift anisotropy in solid-state NMR of rotating solids. The chemical shift interaction is irradiated with two types of radiofrequency pulse sequences: BABA and C7. The criteria for the chemical shift anisotropy to be averaged out in each rotor period are obtained. (C) 2013 Elsevier Inc. All rights reserved. C1 [Mananga, Eugene Stephane] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Mananga, Eugene Stephane] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging Phys, Dept Radiol, Boston, MA 02114 USA. RP Mananga, ES (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM emananga@pet.mgh.harvard.edu FU National Institute of Health (NIH) [R01-HL110241, T32 EB013180] FX E.S. Mananga acknowledges assistance from Massachusetts General Hospital, Harvard Medical School, and the National Institute of Health (NIH), under Grants R01-HL110241 and T32 EB013180. The contents of this paper are solely the responsibility of the authors and do not represent the official views of NIH. NR 34 TC 6 Z9 6 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0926-2040 EI 1527-3326 J9 SOLID STATE NUCL MAG JI Solid State Nucl. Magn. Reson. PD OCT-NOV PY 2013 VL 55-56 BP 63 EP 72 DI 10.1016/j.ssnmr.2013.08.003 PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical; Physics, Condensed Matter; Spectroscopy SC Chemistry; Physics; Spectroscopy GA 254AQ UT WOS:000327132700007 ER PT J AU Cayabyab, MJ Qin, LZ Kashino, SS Izzo, A Campos-Neto, A AF Cayabyab, Mark J. Qin, Lizeng Kashino, Suely S. Izzo, Angelo Campos-Neto, Antonio TI An unbiased peptide-wide discovery approach to select Mycobacterium tuberculosis antigens that target CD8+T cell response during infection SO VACCINE LA English DT Article DE Tuberculosis; CD8 associated antigen; MT0401; Immunogenicity ID CD8(+) T-CELLS; RECOMBINANT ADENOVIRAL VECTORS; IN-VIVO; GAMMA; GENE; VACCINATION; VIRUS; PROTECTION; INDUCTION; PRIMATES AB Accruing data strongly support the possible role of CD8+ T cells in immunity against tuberculosis (TB). Multivalent vaccines against Mycobacterium tuberculosis (Mtb) that incorporate CD8+ T cell antigens with those that elicit CD4+ T cells are therefore highly desirable. To screen for potential CD8+ T cell antigens that are produced by Mtb during infection, we isolated pathogen-derived peptides that bound to MHC Class I molecules expressed in adherent splenocytes obtained from Mtb-infected mice. Mass spectroscopy analysis revealed the following four nonamer peptides that had 100% homology with Mtb proteins: DGYVGAPAH (MT_0401), TTMPLFAD (MT_1164), RSGAATPVR (MT_2160.1) and LAAVVGVVL (MT_0078). The gene MT_0401 codes the protein 5'-phosphoribosylglycinamide transformylase 2 and the other three genes code for hypothetical proteins with unknown function. The NCBI/Blast analysis showed that among the four peptides DGYVGAPAH had the highest maximum alignment score and lowest E value (number of alignments expected by chance). Therefore, we assessed whether MT_0401 expressed in two genetic vaccine formulations was capable of stimulating CD8+ T cell response that is specific to DGYVGAPAH peptide. When mice were immunized with a recombinant plasmid DNA and an E1/E3-deleted Adenovirus 5 expressing MT0401 protein, using both homologous and heterologous prime-boost protocols, they developed strong DGYVGAPAH-specific CD8+ T cell response as well as antibody and CD4+ specific T cell response to the full length MT0401 protein. Equally important was the observation that mice infected with Mtb developed DGYVGAPAH-specific CD8+ T cell responses in both spleen and lungs. These results demonstrate that Mtb antigens that are processed and presented via MHC Class I machinery can be readily identified by the described approach and may be useful candidate antigens to stimulate specific CD8+ T cell responses in vaccine development programs. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Cayabyab, Mark J.; Campos-Neto, Antonio] Forsyth Inst, Global Infect Dis Res Ctr, Cambridge, MA 02142 USA. [Cayabyab, Mark J.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Izzo, Angelo] Colorado State Univ, Dept Pathol & Immunol, Mycobacteria Res Labs, Ft Collins, CO 80523 USA. [Qin, Lizeng] Novartis Corp, Cambridge, MA USA. [Kashino, Suely S.] Adolpho Lutz Inst, Sao Paulo, Brazil. RP Campos-Neto, A (reprint author), Forsyth Inst, Global Infect Dis Res Ctr, 245 1st St, Cambridge, MA 02142 USA. EM acampos@forsyth.org RI Izzo, Angelo/F-1229-2017 OI Izzo, Angelo/0000-0003-3208-2330 FU National Institutes of Health [R01AI076425]; Harvard University Center for AIDS Research FX This work was supported by a grant from the National Institutes of Health to A.C-N (R01AI076425). MC was supported in part by the Harvard University Center for AIDS Research. NR 33 TC 2 Z9 4 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD OCT 1 PY 2013 VL 31 IS 42 BP 4834 EP 4840 DI 10.1016/j.vaccine.2013.07.077 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 249IY UT WOS:000326772100025 PM 23933335 ER PT J AU Jung, M Lin, L Viswanath, K AF Jung, Minsoo Lin, Leesa Viswanath, K. TI Associations between health communication behaviors, neighborhood social capital, vaccine knowledge, and parents' H1N1 vaccination of their children SO VACCINE LA English DT Article DE H1N1; Vaccination; Child; Social determinants; Health communication; Social capital ID INFLUENZA VACCINATION; RISK PERCEPTION; TEACHERS; INEQUALITIES; POPULATION; PREDICTORS; MONOVALENT; STUDENTS; BELIEFS; CANCER AB During the H1N1 pandemic in 2009-10, the vaccination behavior of parents played a critical role in preventing and containing the spread of the disease and the subsequent health outcomes among children. Several studies have examined the relationship between parents' health communication behaviors and vaccinations for children in general. Little is known, however, about the link between parents' health communication behaviors and the vaccination of their children against the H1N1 virus, and their level of vaccine-related knowledge. We drew on a national survey among parents with at least one child less than 18 years of age (n = 639) to investigate Parents' H1N1-related health communication behaviors including sources of information, media exposure, information-seeking behaviors, H1N1-related knowledge, and neighborhood social capital, as well as the H1N1 vaccination rates of their children. Findings showed that there is a significant association between the degree at which parents obtained H1N1 vaccination for their children and health communication variables: watching the national television news and actively seeking H1N1 information. And this association was moderated by the extent of the parents' H1N1-related knowledge. In addition, the parents' degree of neighborhood social capital mediated the association between H1N1 knowledge of the parents and H1N1 vaccination acceptance for their children. We found, compared to those with a low-level of neighborhood social capital, parents who have a high-level of neighborhood social capital are more likely to vaccinate their children. These findings suggest that it is necessary to design a strategic health communication campaign segmented by parent health communication behaviors. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Jung, Minsoo; Lin, Leesa; Viswanath, K.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. [Jung, Minsoo] Dongduk Womens Univ, Dept Hlth Sci, Seoul, South Korea. [Lin, Leesa; Viswanath, K.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. RP Jung, M (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 450 Brookline Ave,LW 601, Boston, MA 02215 USA. EM minsoo_jung@dfci.harvard.edu OI Jung, Minsoo/0000-0003-3317-6507 FU Harvard School of Public Health Preparedness and Emergency Response Center (Harvard PERRC), CDC [5PO1TP000307-05] FX This project was funded by the Harvard School of Public Health Preparedness and Emergency Response Center (Harvard PERRC) - Linking Assessment and Measurement to Performance in PHEP Systems (LAMPS), CDC grant number: 5PO1TP000307-05. The content of this publication as well as the views and discussions expressed in this paper are solely those of the authors and do not necessarily represent the views of any partner organizations, the CDC or the U.S. Department of Health and Human Services nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government. NR 37 TC 15 Z9 15 U1 1 U2 24 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 OCT 1 PY 2013 VL 31 IS 42 BP 4860 EP 4866 DI 10.1016/j.vaccine.2013.07.068 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 249IY UT WOS:000326772100029 PM 23954379 ER PT J AU Robinson, TN Wu, DS Pointer, L Dunn, CL Cleveland, JC Moss, M AF Robinson, Thomas N. Wu, Daniel S. Pointer, Lauren Dunn, Christina L. Cleveland, Joseph C., Jr. Moss, Marc TI Simple frailty score predicts postoperative complications across surgical specialties SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Geriatric surgery; Preoperative risk assessment; Surgical morbidity ID OLDER-ADULTS; NONCARDIAC SURGERY; ELDERLY-PATIENTS; CO-MORBIDITY; CARE; MORTALITY; RISK; POPULATION; VALIDATION; SEVERITY AB BACKGROUND: Our purpose was to determine the relationship between preoperative frailty and the occurrence of postoperative complications after colorectal and cardiac operations. METHODS: Patients 65 years or older undergoing elective colorectal or cardiac surgery were enrolled. Seven baseline frailty traits were measured preoperatively: Katz score less than or equal to 5, Timed Up and Go test greater than or equal to 15 seconds, Charlson Index greater than or equal to 3, anemia less than 35%, Mini-Cog score less than or equal to 3, albumin less than 3.4 g/dL, and 1 or more falls within 6 months. Patients were categorized by the number of positive traits as follows: non-frail: 0 to 1 traits, prefrail: 2 to 3 traits, and frail: 4 or more traits. RESULTS: Two hundred one subjects (age 74 +/- 6 years) were studied. Preoperative frailty was associated with increased postoperative complications after colorectal (nonfrail: 21%, prefrail: 40%, frail: 58%; P = .016) and cardiac operations (nonfrail: 17%, prefrail: 28%, frail: 56%; P < .001). This finding in both groups was independent of advancing age. Frail individuals in both groups had longer hospital stays and higher 30-day readmission rates. Receiver operating characteristic curves examining frailty's ability to forecast complications were colorectal (.702, P = .004) and cardiac (. 711, P < .001). CONCLUSIONS: A simple preoperative frailty score defines older adults at higher risk for postoperative complications across surgical specialties. Published by Elsevier Inc. C1 [Robinson, Thomas N.; Wu, Daniel S.; Dunn, Christina L.; Cleveland, Joseph C., Jr.] Univ Colorado Denver Sch Med, Dept Surg, Aurora, CO 80045 USA. [Moss, Marc] Univ Colorado Denver Sch Med, Dept Med, Aurora, CO 80045 USA. [Robinson, Thomas N.; Wu, Daniel S.; Cleveland, Joseph C., Jr.] Denver Vet Affairs Med Ctr, Dept Surg, Denver, CO USA. [Pointer, Lauren] Denver Vet Affairs Med Ctr, Dept Biostat, Denver, CO USA. RP Robinson, TN (reprint author), Univ Colorado Denver Sch Med, Dept Surg, 12631 East 17th Ave,MS C313, Aurora, CO 80045 USA. EM thomas.robinson@ucdenver.edu FU Paul B. Beeson Award [NIA K23AG034632]; Dennis W. Jahnigen Award; American Geriatrics Society; National Institutes of Health [K24-HL-089223] FX Supported by the Paul B. Beeson Award (NIA K23AG034632 [TNR]), Dennis W. Jahnigen Award, American Geriatrics Society (TNR) and National Institutes of Health (K24-HL-089223 [MM]). NR 26 TC 76 Z9 76 U1 3 U2 11 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD OCT PY 2013 VL 206 IS 4 BP 544 EP 550 DI 10.1016/j.amjsurg.2013.03.012 PG 7 WC Surgery SC Surgery GA 246BF UT WOS:000326510500016 PM 23880071 ER PT J AU An, HM Tan, YL Shi, J Wang, ZR Li, J Wang, YC Kosten, TR Zhou, DF Yang, FD Zhang, XY AF An, Hui-Mei Tan, Yun-Long Shi, Jing Wang, Zhi-Ren Li, Jia Wang, Yue-Chan Kosten, Thomas R. Zhou, Dong Feng Yang, Fu-De Zhang, Xiang-Yang TI Extract of Ginkgo biloba is equivalent to vitamin E in attenuating and preventing vacuous chewing movements in a rat model of tardive dyskinesia SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE animal model; antioxidant; extract of Ginkgo biloba; free radical; rat; tardive dyskinesia; vacuous chewing movements; vitamin E ID INDUCED OROFACIAL DYSKINESIA; PLACEBO-CONTROLLED TRIAL; LONG-TERM TREATMENT; DOUBLE-BLIND; JAW MOVEMENTS; POSSIBLE INVOLVEMENT; ANIMAL-MODELS; SUPEROXIDE-DISMUTASE; PARKINSONIAN TREMOR; OXIDATIVE STRESS AB Free radical-mediated abnormalities may contribute toward the pathogenesis of tardive dyskinesia (TD). Many studies have reported the protective antioxidant and free radical-scavenging activities of extract of Ginkgo biloba (EGb761) against free radical-induced cell damage and dysfunction. This study aimed to compare the efficacy of EGb761 with that of vitamin E for the prevention and treatment of TD in a rat model. We carried out two studies. First, rats were injected with haloperidol (2 mg/kg intraperitoneally) daily for 5 weeks. EGb761 (50mg/kg/day) or vitamin E (20mg/kg/day) were then administered for another 5 weeks, and their effects on vacuous chewing movements (VCMs) were compared. Second, we compared 10 weeks of haloperidol alone with 10 weeks of haloperidol plus EGb761 or vitamin E. The administration of haloperidol led to a progressive increase in VCMs, which peaked at week 5. In study one, EGb761 and vitamin E, administered by an oral gavage for 5 weeks during withdrawal from chronic haloperidol treatment, decreased VCMs significantly, showing 83.8 and 91.0% reduction, respectively, compared with the haloperidol-alone group. In study two, the concomitant administration of EGb761 and vitamin E led to significantly fewer VCMs, by 64.4 and 73.9%, respectively, compared with the haloperidol-alone group. There was no significant difference in either study between EGb761 and vitamin E treatment. EGb761 shows promise for the prevention and treatment of TD in a rat model with a magnitude that was similar to that of vitamin E. (C) 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [An, Hui-Mei; Tan, Yun-Long; Shi, Jing; Wang, Zhi-Ren; Li, Jia; Wang, Yue-Chan; Yang, Fu-De; Zhang, Xiang-Yang] Peking Univ, Beijing Huilongguan Hosp, Psychiat Res Ctr, Beijing 100871, Peoples R China. [Zhou, Dong Feng] Peking Univ, Inst Mental Hlth, Beijing 100871, Peoples R China. [Kosten, Thomas R.; Zhang, Xiang-Yang] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Kosten, Thomas R.; Zhang, Xiang-Yang] Michael E DeBakey VA Med Ctr, Houston, TX USA. RP Zhang, XY (reprint author), VA Med Ctr, Res Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. EM xyzhang@bcm.edu FU National Natural Science Foundation of China [30770782, 81071086]; Stanley Medical Research Institute [03T-459, 05T-726]; United States National Institute of Health [K05-DA0454, P50-DA18827, U01-MH79639] FX This work was supported by grants from the National Natural Science Foundation of China (30770782, 81071086), the Stanley Medical Research Institute (03T-459 and 05T-726), and the United States National Institute of Health K05-DA0454, P50-DA18827 and U01-MH79639. NR 71 TC 3 Z9 3 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 EI 1473-5849 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD OCT PY 2013 VL 24 IS 7 BP 610 EP 616 DI 10.1097/FBP.0b013e3283656d87 PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 251YP UT WOS:000326971200008 PM 23994817 ER PT J AU Johnson, GJ Leis, LA Slater, BCS Bach, RR AF Johnson, Gerhard J. Leis, Linda A. Slater, Billie C. S. Bach, Ronald R. TI Elevated platelet count, C-reactive protein and thromboxane analog-induced platelet aggregation in patients with Gulf War veterans' illnesses: evidence of a chronic inflammatory state? SO BLOOD COAGULATION & FIBRINOLYSIS LA English DT Article DE C-reactive protein; Gulf War illness; platelet aggregation; platelet secretion; thromboxane A(2) ID CHRONIC-FATIGUE-SYNDROME; THROMBOCYTOSIS; DYSFUNCTION; ACTIVATION; LINK AB A previous study of Gulf War veteran's illnesses (GWVI) observed evidence of platelet activation in a majority of patients with GWVI. To further characterize platelet function, we studied 43 patients (40 men) with GWVI (GWVI+) and 21 veterans who served concurrently in the Gulf War but who lacked criteria for GWVI (GWVI-). All participants were free of infection and known inflammatory diseases. Studies performed included platelet count, immature platelet fraction (IPF), plasma thrombopoietin (TPO), C-reactive protein (CRP), platelet aggregation and ATP secretion in response to six agonists, and spontaneous aggregation. Platelet counts and CRP were significantly elevated in GWVI+ compared to GWVI- patients without elevation in IPF or TPO. Platelet aggregation did not differ between GWVI+ and GWVI- patients except for spontaneous aggregation that was significantly greater in GWVI+ patients. Platelet ATP secretion was similar in the two groups, except the response to 50mol/l thrombin receptor agonist peptide 6 (TRAP 6) was significantly greater in GWVI+ patients. When platelet aggregation was analyzed in relation to CRP, the response to 0.5mol/l U46619 was significantly greater in patients whose CRP was at least 2g/ml. Therefore, GWVI+ patients had elevated platelet counts, spontaneous aggregation, TRAP 6-induced secretion, and CRP, but no impairment of platelet function. The increased platelet counts and U46619-induced aggregation appear to be consequences of an underlying inflammatory state in GWVI. (C) 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Johnson, Gerhard J.; Leis, Linda A.; Slater, Billie C. S.; Bach, Ronald R.] VA Healthcare Syst, Minneapolis, MN 55417 USA. [Johnson, Gerhard J.; Leis, Linda A.; Slater, Billie C. S.; Bach, Ronald R.] Univ Minnesota, Minneapolis, MN USA. [Leis, Linda A.; Slater, Billie C. S.; Bach, Ronald R.] Univ Minnesota, US Dept Vet Affairs, Res Serv, Minneapolis, MN USA. [Johnson, Gerhard J.] Univ Minnesota, Dept Med, Div Hematol Oncol & Transplant, Minneapolis, MN 55455 USA. RP Johnson, GJ (reprint author), VA Healthcare Syst, Hematol Oncol 111E,1 Vet Dr, Minneapolis, MN 55417 USA. EM johns337@umn.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development; US Department of Defense, Gulf War Illness Research Programs FX Source of support for the work: This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and by the US Department of Defense, Gulf War Illness Research Programs. NR 25 TC 5 Z9 5 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-5235 EI 1473-5733 J9 BLOOD COAGUL FIBRIN JI Blood Coagul. Fibrinolysis PD OCT PY 2013 VL 24 IS 7 BP 736 EP 741 DI 10.1097/MBC.0b013e328362627f PG 6 WC Hematology SC Hematology GA 247EM UT WOS:000326598300011 PM 23751609 ER PT J AU Singh, H AF Singh, Hardeep TI Diagnostic errors: moving beyond 'no respect' and getting ready for prime time SO BMJ QUALITY & SAFETY LA English DT Editorial Material DE Accreditation; Adverse events; epidemiology and detection; Ambulatory care ID PRIMARY-CARE; INFORMATION-TECHNOLOGY; MISSED OPPORTUNITIES; MALPRACTICE CLAIMS; CANCER DIAGNOSIS; PATIENT-SAFETY; SETTINGS; MEDICINE; AUTOPSY; RECORDS C1 [Singh, Hardeep] Baylor Coll Med, Houston VA HSR&D Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, VA Med Ctr, Houston, TX 77030 USA. [Singh, Hardeep] Baylor Coll Med, VA Med Ctr, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. RP Singh, H (reprint author), Baylor Coll Med, Houston VA HSR&D Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, VA Med Ctr, 152 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.edu FU AHRQ HHS [R18HS017820, R13 HS019252, R13 HS19252-01, R18 HS017820]; NCI NIH HHS [K23 CA125585, K23CA125585] NR 39 TC 9 Z9 9 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD OCT PY 2013 VL 22 IS 10 BP 789 EP 792 DI 10.1136/bmjqs-2013-002387 PG 4 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 247XU UT WOS:000326659100001 PM 24048615 ER PT J AU Hariri, LP Mino-Kenudson, M Applegate, MB Mark, EJ Tearney, GJ Lanuti, M Channick, CL Chee, A Suter, MJ AF Hariri, Lida P. Mino-Kenudson, Mari Applegate, Matthew B. Mark, Eugene J. Tearney, Guillermo J. Lanuti, Michael Channick, Colleen L. Chee, Alex Suter, Melissa J. TI Toward the Guidance of Transbronchial Biopsy Identifying Pulmonary Nodules With Optical Coherence Tomography SO CHEST LA English DT Article ID GUIDELINES 2ND EDITION; LUNG-CANCER; IN-VIVO; BARRETTS-ESOPHAGUS; BRONCHIAL LESIONS; NEEDLE; DIAGNOSIS; BRONCHOSCOPY; MICROSCOPY; METAANALYSIS AB Background: Solitary pulmonary nodules (SPNs) frequently require transbronchial needle aspiration (TBNA) or biopsy to determine malignant potential, but have variable diagnostic yields. Confirming needle placement within SPNs during TBNA could significantly increase diagnostic yield. Optical coherence tomography (OCT) provides nondestructive, high-resolution, microstructural imaging with potential to distinguish SPN from parenchyma. We have developed needle-based OCT probes compatible with TBNA. Before OCT can play any significant role in guiding clinical TBNA, OCT interpretation criteria for differentiating SPN from lung parenchyma must be developed and validated. Methods: OCT of SPN and parenchyma was performed on 111 ex vivo resection specimens. OCT criteria for parenchyma and SPN were developed and validated in a blinded assessment. Six blinded readers (two pulmonologists, two pathologists, and two OCT experts) were trained on imaging criteria in a 15-min training session prior to interpreting the validation data set. Results: OCT of lung parenchyma displayed evenly spaced signal-void alveolar spaces, signal-intense backreflections at tissue-air interfaces, or both. SPNs lacked both of these imaging features. Independent validation of OCT criteria by the six blinded readers demonstrated sensitivity and specificity of 95.4% and 98.2%, respectively. Conclusions: We have developed and validated OCT criteria for lung parenchyma and SPN with sensitivity and specificity. 95% in this ex vivo study. We anticipate that OCT could be a useful complementary imaging modality to confirm needle placement during TBNA to potentially increase diagnostic yield. C1 [Hariri, Lida P.; Mino-Kenudson, Mari; Mark, Eugene J.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Applegate, Matthew B.; Channick, Colleen L.; Chee, Alex; Suter, Melissa J.] Massachusetts Gen Hosp, Dept Pulm, Boston, MA 02114 USA. [Applegate, Matthew B.; Channick, Colleen L.; Chee, Alex; Suter, Melissa J.] Massachusetts Gen Hosp, Crit Care Unit, Boston, MA 02114 USA. [Hariri, Lida P.; Applegate, Matthew B.; Tearney, Guillermo J.; Chee, Alex; Suter, Melissa J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Lanuti, Michael] Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. [Hariri, Lida P.; Mino-Kenudson, Mari; Mark, Eugene J.; Tearney, Guillermo J.; Lanuti, Michael; Channick, Colleen L.; Suter, Melissa J.] Harvard Univ, Sch Med, Boston, MA USA. [Tearney, Guillermo J.] Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. RP Suter, MJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Warren Bldg,Room 407, Boston, MA 02114 USA. EM msuter@partners.org FU National Institutes of Heath [R00CA134920, R01CA167827, P41EB01593]; American Lung Association [RG-194681-N] FX This work was funded in part by the National Institutes of Heath [Grants R00CA134920, R01CA167827, P41EB01593] and the American Lung Association [Grant RG-194681-N]. NR 47 TC 10 Z9 10 U1 0 U2 12 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 EI 1931-3543 J9 CHEST JI Chest PD OCT PY 2013 VL 144 IS 4 BP 1261 EP 1268 DI 10.1378/chest.13-0534 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 241JJ UT WOS:000326162600031 PM 23828441 ER PT J AU Daniel, S Soleymani, T Garvey, WT AF Daniel, Sunil Soleymani, Taraneh Garvey, W. Timothy TI A complications-based clinical staging of obesity to guide treatment modality and intensity SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Review DE cardiometabolic disease; complications; obesity; treatment algorithm; weight loss ID BODY-MASS INDEX; OBSTRUCTIVE SLEEP-APNEA; QUALITY-OF-LIFE; POLYCYSTIC-OVARY-SYNDROME; FATTY LIVER-DISEASE; BINGE-EATING DISORDER; CONTROLLED-RELEASE PHENTERMINE/TOPIRAMATE; GASTROESOPHAGEAL-REFLUX DISEASE; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL AB Purpose of reviewThe current medical model for obesity management is BMI-centric because BMI is the predominant measure used to gauge disease severity, as well as indications for various treatment modalities. Recent advancements in therapy and understanding of the relationship between BMI and obesity-related complications call for a re-examination of this approach.Recent findingsAdvancements in treatment, including the recent approval of two new weight loss medications in the USA, have enabled development of new medical models for management of obesity. On the basis of accumulating data demonstrating the benefits of weight loss regarding multiple obesity-related complications (e.g., diabetes prevention, type 2 diabetes mellitus, cardiovascular disease risk, nonalcoholic steatohepatitis, sleep apnea), a complications-centric model is proposed that employs weight loss as a tool to treat and prevent obesity comorbidities. This model assures that the aggressiveness of therapy is commensurate with disease severity, and that therapy is directed at those obese patients who will benefit most from weight loss therapy. The treatment algorithm is comprehensive in addressing complications and quantitative when possible in the staging of risk or disease severity.SummaryA complications-centric approach to obesity management identifies patients who will benefit most from weight loss, and optimizes patient outcomes, benefit/risk ratio, and the cost-effectiveness of interventions. C1 [Daniel, Sunil] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, MA USA. RP Daniel, S (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, Webb 232,1720 2nd Ave South, Birmingham, AL 35294 USA. EM sunild@uab.edu FU Department of Veterans Affairs; National Institutes of Health [DK-038765, DK-083562]; UAB Diabetes Research Center [P60-DK079626]; Merck; Amylin; Weight Watchers FX This work was supported by the Merit Review program of the Department of Veterans Affairs, the National Institutes of Health (DK-038765 and DK-083562), and the UAB Diabetes Research Center (P60-DK079626).; W.T.G. is a speaker for Merck, Amylin, and Liposcience. He is on the advisory boards of Daiichi-Sankyo, Vivus, Alkermes, Eisai, Liposcience, Tethys Bioscience, and Janssen. He receives research support from Merck, Amylin, and Weight Watchers. S. D. is a speaker for Vivus. T. S. is a speaker for Vivus. NR 130 TC 11 Z9 11 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X EI 1752-2978 J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD OCT PY 2013 VL 20 IS 5 BP 377 EP 388 DI 10.1097/01.med.0000433067.01671.f5 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 247BG UT WOS:000326587900003 PM 23974764 ER PT J AU Nichols, JJ Willcox, MDP Bron, AJ Belmonte, C Ciolino, JB Craig, JP Dogru, M Foulks, GN Jones, L Nelson, JD Nichols, KK Purslow, C Schaumberg, DA Stapleton, F Sullivan, DA AF Nichols, Jason J. Willcox, Mark D. P. Bron, Anthony J. Belmonte, Carlos Ciolino, Joseph B. Craig, Jennifer P. Dogru, Murat Foulks, Gary N. Jones, Lyndon Nelson, J. Daniel Nichols, Kelly K. Purslow, Christine Schaumberg, Debra A. Stapleton, Fiona Sullivan, David A. CA TFOS Int Workshop Contact Lens TI The TFOS International Workshop on Contact Lens Discomfort: Executive Summary SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Editorial Material DE contact lenses; dry eye; discomfort; dryness; discontinuation C1 [Nichols, Jason J.; Nichols, Kelly K.] Univ Houston, Coll Optometry, Ocular Surface Inst, Houston, TX 77204 USA. [Willcox, Mark D. P.; Stapleton, Fiona] Univ New S Wales, Sch Optometry & Vis Sci, Sydney, NSW, Australia. [Bron, Anthony J.] Univ Oxford, Nuffield Lab Ophthalmol, Oxford OX2 6AW, England. [Belmonte, Carlos] Univ Miguel Hernandez, Inst Neurociencias, CSIC, Alicante, Spain. [Belmonte, Carlos] Fdn Invest Oftalmol, Inst Fernandez Vega, Oviedo, Spain. [Ciolino, Joseph B.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Craig, Jennifer P.] Univ Auckland, Dept Ophthalmol, Auckland 1, New Zealand. [Dogru, Murat] Ichikawa Hosp, Tokyo Dent Coll, Tokyo, Japan. [Foulks, Gary N.] Univ Louisville, Dept Ophthalmol & Visual Sci, Kentucky Lions Eye Ctr, Louisville, KY 40292 USA. [Jones, Lyndon] Univ Waterloo, Sch Optometry & Vis Sci, Ctr Contact Lens Res, Waterloo, ON N2L 3G1, Canada. [Nelson, J. Daniel] Hlth Partners Med Grp, Minneapolis, MN USA. [Purslow, Christine] Univ Plymouth, Peninsula Allied Hlth Ctr, Plymouth PL4 8AA, Devon, England. [Schaumberg, Debra A.] Univ Utah, Sch Med, Dept Ophthalmol & Visual Sci, Moran Ctr Translat Med,John A Moran Eye Ctr, Salt Lake City, UT USA. [Sullivan, David A.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Massachusetts Eye & Ear, Boston, MA USA. RP Nichols, JJ (reprint author), Univ Houston, Coll Optometry, Ocular Surface Inst, 505 J Davis Armistead Bldg,4901 Calhoun Rd, Houston, TX 77204 USA. EM jnichols@optometry.uh.edu OI Golebiowski, Blanka/0000-0002-9348-6470; Nichols, Jason/0000-0003-1519-7734 NR 0 TC 27 Z9 27 U1 2 U2 9 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2013 VL 54 IS 11 SI SI BP 7 EP 13 DI 10.1167/iovs.13-13212 PG 7 WC Ophthalmology SC Ophthalmology GA 247KW UT WOS:000326617300002 ER PT J AU Stapleton, F Marfurt, C Golebiowski, B Rosenblatt, M Bereiter, D Begley, C Dartt, D Gallar, J Belmonte, C Hamrah, P Willcox, M AF Stapleton, Fiona Marfurt, Carl Golebiowski, Blanka Rosenblatt, Mark Bereiter, David Begley, Carolyn Dartt, Darlene Gallar, Juana Belmonte, Carlos Hamrah, Pedram Willcox, Mark CA TFOS Int Workshop Contact Lens TI The TFOS International Workshop on Contact Lens Discomfort: Report of the Subcommittee on Neurobiology SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT 7th International Conference on the Tear Film and Ocular Surface-Basic Science and Clinical Relevance (TFOS) CY SEP 18-21, 2013 CL Taormina, ITALY DE contact lens; dry eye; discomfort; neurobiology ID NERVE GROWTH-FACTOR; IN-SITU KERATOMILEUSIS; SPINAL TRIGEMINAL NUCLEUS; NONCONTACT CORNEAL AESTHESIOMETER; PLATELET-ACTIVATING-FACTOR; FOS-LIKE IMMUNOREACTIVITY; VIVO CONFOCAL MICROSCOPY; DRY EYE SYMPTOMS; POLYMORPHONUCLEAR LEUKOCYTE RESPONSE; PHOTOREFRACTIVE KERATECTOMY PAIN AB This report characterizes the neurobiology of the ocular surface and highlights relevant mechanisms that may underpin contact lens-related discomfort. While there is limited evidence for the mechanisms involved in contact lens-related discomfort, neurobiological mechanisms in dry eye disease, the inflammatory pathway, the effect of hyperosmolarity on ocular surface nociceptors, and subsequent sensory processing of ocular pain and discomfort have been at least partly elucidated and are presented herein to provide insight in this new arena. The stimulus to the ocular surface from a contact lens is likely to be complex and multifactorial, including components of osmolarity, solution effects, desiccation, thermal effects, inflammation, friction, and mechanical stimulation. Sensory input will arise from stimulation of the lid margin, palpebral and bulbar conjunctiva, and the cornea. C1 [Stapleton, Fiona; Golebiowski, Blanka; Willcox, Mark] Univ New S Wales, Sch Optometry & Vis Sci, Sydney, NSW 2052, Australia. [Marfurt, Carl] Indiana Univ Sch Med Northwest, Gary, IN USA. [Rosenblatt, Mark] Cornell Univ, Weill Cornell Med Coll, Ithaca, NY USA. [Bereiter, David] Univ Minnesota, Sch Dent, Minneapolis, MN 55455 USA. [Begley, Carolyn] Indiana Univ, Sch Optometry, Bloomington, IN USA. [Dartt, Darlene] Harvard Univ, Sch Med, Schepens Eye Res Inst, Massachusetts Eye & Ear, Boston, MA USA. [Gallar, Juana; Belmonte, Carlos] Univ Miguel Hernandez, Inst Neurociencias Alicante, CSIC, Alicante, Spain. [Hamrah, Pedram] Massachusetts Eye & Ear Infirm, Stoneham, MA USA. RP Willcox, M (reprint author), Univ New S Wales, Sch Optometry & Vis Sci, Sydney, NSW 2052, Australia. EM mdpwillcox@gmail.com RI Gallar, Juana/B-4563-2011; OI Gallar, Juana/0000-0002-3559-3649; Golebiowski, Blanka/0000-0002-9348-6470 NR 401 TC 20 Z9 20 U1 0 U2 16 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2013 VL 54 IS 11 SI SI BP 71 EP 97 DI 10.1167/iovs.13-13226 PG 27 WC Ophthalmology SC Ophthalmology GA 247KW UT WOS:000326617300006 ER PT J AU Papas, EB Ciolino, JB Jacobs, D Miller, WS Pult, H Sahin, A Srinivasan, S Tauber, J Wolffsohn, JS Nelson, JD AF Papas, Eric B. Ciolino, Joseph B. Jacobs, Deborah Miller, William S. Pult, Heiko Sahin, Afsun Srinivasan, Sruthi Tauber, Joseph Wolffsohn, James S. Nelson, J. Daniel CA TFOS Int Workshop Contact Lens TI The TFOS International Workshop on Contact Lens Discomfort: Report of the Management and Therapy Subcommittee SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT 7th International Conference on the Tear Film and Ocular Surface-Basic Science and Clinical Relevance (TFOS) CY SEP 18-21, 2013 CL Taormina, ITALY DE contact; dry eyes; tears; discomfort ID MEIBOMIAN GLAND DYSFUNCTION; SILICONE-HYDROGEL LENSES; DRY EYE SYNDROME; QUALITY-OF-LIFE; TOPICAL CYCLOSPORINE 0.05-PERCENT; CONJUNCTIVAL IMPRESSION CYTOLOGY; CONTROLLED ADVERSE ENVIRONMENT; OPHTHALMIC SOLUTION 1-PERCENT; PATIENT-RELATED FACTORS; OCULAR SURFACE DISEASE C1 [Papas, Eric B.] Brien Holden Vis Inst, Sydney, NSW, Australia. [Papas, Eric B.] Vis CRC, Sydney, NSW, Australia. [Papas, Eric B.] Univ New S Wales, Sch Optometry & Vis Sci, Sydney, NSW, Australia. [Ciolino, Joseph B.; Jacobs, Deborah] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Jacobs, Deborah] Boston Fdn Sight, Needham, MA USA. [Miller, William S.] Univ Houston, Coll Optometry, Dept Clin Sci, Ocular Surface Inst, Houston, TX USA. [Pult, Heiko] Dr Heiko Pult Optometry & Vis Res, Weinheim, Germany. [Pult, Heiko] Cardiff Univ, Sch Optometry & Vis Sci, Cardiff, S Glam, Wales. [Sahin, Afsun] Eskisehir Osmangazi Univ, Sch Med, Dept Ophthalmol, Eskisehir, Turkey. [Srinivasan, Sruthi] Univ Waterloo, Sch Optometry & Vis Sci, Ctr Contact Lens Res, Waterloo, ON N2L 3G1, Canada. [Tauber, Joseph] Tauber Eye Ctr, Kansas City, MO USA. [Wolffsohn, James S.] Aston Univ, Ophthalm Res Grp, Birmingham B4 7ET, W Midlands, England. [Nelson, J. Daniel] HealthPartners Med Grp, Minneapolis, MN 55440 USA. RP Nelson, JD (reprint author), HealthPartners Med Grp, Mail Stop 21110R,POB 1309, Minneapolis, MN 55440 USA. EM j.d.nelson@healthpartners.com RI Pult, Heiko/I-3596-2015 OI Pult, Heiko/0000-0003-4371-8007 NR 278 TC 11 Z9 11 U1 1 U2 12 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2013 VL 54 IS 11 SI SI BP 183 EP 203 DI 10.1167/iovs.13-13166 PG 21 WC Ophthalmology SC Ophthalmology GA 247KW UT WOS:000326617300010 ER PT J AU Parissi, M Karanis, G Randjelovic, S Germundsson, J Poletti, E Ruggeri, A Utheim, TP Lagali, N AF Parissi, Marlen Karanis, Georgios Randjelovic, Stefan Germundsson, Johan Poletti, Enea Ruggeri, Alfredo Utheim, Tor Paaske Lagali, Neil TI Standardized Baseline Human Corneal Subbasal Nerve Density for Clinical Investigations With Laser-Scanning in Vivo Confocal Microscopy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE subbasal nerve; imaging; confocal microscopy ID STEM-CELL DEFICIENCY; FLUORESCENCE MICROSCOPY; DIABETIC-NEUROPATHY; INNERVATION; PLEXUS; IMAGES; SENSITIVITY; TORTUOSITY; DYSTROPHY AB PURPOSE. We established a baseline value for central corneal subbasal nerve density in a large, healthy cohort. METHODS. A total of 106 healthy volunteers (207 eyes) underwent full ophthalmic examination, including laser-scanning in vivo confocal microscopy (IVCM) of the central cornea. Images of the corneal subbasal nerve plexus were acquired and analyzed based on defined criteria. Nerve tracing was performed by two human observers and by a fully automated method. Subbasal nerve density was stratified by eye, observer, tracing method, calculation method, and age group. Association of nerve density with age was examined by linear regression and population distribution was examined by nonlinear regression. RESULTS. We analyzed 892 distinct, high quality images of the subbasal nerve plexus (mean, 4.3 images/eye) from 207 eyes. An overall mean central subbasal nerve density of 19 mm/mm(2) was found in 106 subjects aged 15 to 88 years, independent of eye, sex, or nerve tracing method, while the SD was a consistent 4 to 5 mm/mm2. Subbasal nerve density followed a normal Gaussian distribution, and correlated negatively with age, with a mean decline of 0.25% to 0.30% per year, independent of eye, observer, or nerve tracing method. Moreover, the use of automated tracing techniques and randomized sampling may improve the speed and reproducibility of subbasal nerve density assessment for clinical applications. CONCLUSIONS. A baseline human corneal subbasal nerve density has been determined by laser-scanning IVCM using rigorous methods. The methods and results could aid in the future assessment of corneal nerves in various patient populations. C1 [Parissi, Marlen; Utheim, Tor Paaske] Oslo Univ Hosp, Dept Med Biochem, Oslo, Norway. [Parissi, Marlen; Randjelovic, Stefan; Utheim, Tor Paaske] Norwegian Dry Eye Clin, Oslo, Norway. [Karanis, Georgios; Germundsson, Johan; Lagali, Neil] Linkoping Univ, Dept Clin & Expt Med, S-58183 Linkoping, Sweden. [Poletti, Enea; Ruggeri, Alfredo] Univ Padua, Dept Informat Engn, Padua, Italy. [Utheim, Tor Paaske] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA USA. RP Lagali, N (reprint author), Linkoping Univ, Fac Hlth Sci, Dept Clin & Expt Med Ophthalmol, S-58183 Linkoping, Sweden. EM neil.lagali@liu.se OI Lagali, Neil/0000-0003-1079-4361 FU Cronqvist Foundation; Swedish Research Council; Princess Margaretas Foundation for the Visually Impaired; Norwegian Research Council FX Supported by the Cronqvist Foundation, the Swedish Research Council, and Princess Margaretas Foundation for the Visually Impaired (NL), and funding from the Norwegian Research Council (MP). The authors alone are responsible for the content and writing of the paper. NR 38 TC 15 Z9 15 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2013 VL 54 IS 10 BP 7091 EP 7102 DI 10.1167/iovs.13-12999 PG 12 WC Ophthalmology SC Ophthalmology GA 246VI UT WOS:000326567700074 PM 24084094 ER PT J AU Tabach, Y Golan, T Hernandez-Hernandez, A Messer, AR Fukuda, T Kouznetsova, A Liu, JG Lilienthal, I Levy, C Ruvkun, G AF Tabach, Yuval Golan, Tamar Hernandez-Hernandez, Abrahan Messer, Arielle R. Fukuda, Tomoyuki Kouznetsova, Anna Liu, Jian-Guo Lilienthal, Ingrid Levy, Carmit Ruvkun, Gary TI Human disease locus discovery and mapping to molecular pathways through phylogenetic profiling SO MOLECULAR SYSTEMS BIOLOGY LA English DT Article ID RBP-J; FUNCTIONAL-RELATIONSHIPS; PROTEIN INTERACTIONS; GENE-EXPRESSION; COMPLEX; EVOLUTION; MELANOMA; ONCOGENE; CANCER; CILIA AB Genes with common profiles of the presence and absence in disparate genomes tend to function in the same pathway. By mapping all human genes into about 1000 clusters of genes with similar patterns of conservation across eukaryotic phylogeny, we determined that sets of genes associated with particular diseases have similar phylogenetic profiles. By focusing on those human phylogenetic gene clusters that significantly overlap some of the thousands of human gene sets defined by their coexpression or annotation to pathways or other molecular attributes, we reveal the evolutionary map that connects molecular pathways and human diseases. The other genes in the phylogenetic clusters enriched for particular known disease genes or molecular pathways identify candidate genes for roles in those same disorders and pathways. Focusing on proteins coevolved with the microphthalmia-associated transcription factor (MITF), we identified the Notch pathway suppressor of hairless (RBP-Jk/SuH) transcription factor, and showed that RBP-Jk functions as an MITF cofactor. C1 [Tabach, Yuval; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Tabach, Yuval; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Golan, Tamar; Messer, Arielle R.; Levy, Carmit] Tel Aviv Univ, Sackler Fac Med, Dept Human Genet & Biochem, IL-69978 Tel Aviv, Israel. [Hernandez-Hernandez, Abrahan; Fukuda, Tomoyuki; Kouznetsova, Anna; Liu, Jian-Guo; Lilienthal, Ingrid] Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden. RP Tabach, Y (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM tabach@molbio.mgh.harvard.edu; carmitlevy@post.tau.ac.il; ruvkun@molbio.mgh.harvard.edu FU NIH [R01GM44619]; Israeli Centers for Research Excellence (I-CORE); Israel Cancer Association (ICA), Israel Cancer Research Fund (ICRF); USIsrael Binational Science Fund (BSF); Fritz Thyssen Stiftung, Marie Curie Career Integration Grants (CIG); German Cancer Research Center (DKFZ) FX We thank Jonathan Urbach, Sunil Wadhwa, and the Ruvkun laboratory members for the comments and suggestions that have been helpful to improve the manuscript. YTand GR supported by NIH R01GM44619. CL thanks Meenhard Herlyn and Levi Garraway forsupplying melanoma short-term cultures. TG and CL supported by grants from the Israeli Centers for Research Excellence (I-CORE), Israel Cancer Association (ICA), Israel Cancer Research Fund (ICRF), USIsrael Binational Science Fund (BSF), Fritz Thyssen Stiftung, Marie Curie Career Integration Grants (CIG), German Cancer Research Center (DKFZ). NR 59 TC 9 Z9 9 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PD OCT PY 2013 VL 9 AR UNSP 692 DI 10.1038/msb.2013.50 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 248VR UT WOS:000326733900003 PM 24084807 ER PT J AU Cheng, CS Rai, K Garber, M Hollinger, A Robbins, D Anderson, S Macbeth, A Tzou, A Carneiro, MO Raychowdhury, R Russ, C Hacohen, N Gershenwald, JE Lennon, N Nusbaum, C Chin, L Regev, A Amit, I AF Cheng, Christine S. Rai, Kunal Garber, Manuel Hollinger, Andrew Robbins, Dana Anderson, Scott Macbeth, Alyssa Tzou, Austin Carneiro, Mauricio O. Raychowdhury, Raktima Russ, Carsten Hacohen, Nir Gershenwald, Jeffrey E. Lennon, Niall Nusbaum, Chad Chin, Lynda Regev, Aviv Amit, Ido TI Semiconductor-based DNA sequencing of histone modification states SO NATURE COMMUNICATIONS LA English DT Article ID EMBRYONIC STEM-CELLS; LIMITED NUMBERS; CHIP-SEQ; CANCER; INFLAMMATION; REGULATORS; SIGNATURE; POLYCOMB; ENCODE AB The recent development of a semiconductor-based, non-optical DNA sequencing technology promises scalable, low-cost and rapid sequence data production. The technology has previously been applied mainly to genomic sequencing and targeted re-sequencing. Here we demonstrate the utility of Ion Torrent semiconductor-based sequencing for sensitive, efficient and rapid chromatin immunoprecipitation followed by sequencing (ChIP-seq) through the application of sample preparation methods that are optimized for ChIP-seq on the Ion Torrent platform. We leverage this method for epigenetic profiling of tumour tissues. C1 [Cheng, Christine S.; Garber, Manuel; Hollinger, Andrew; Robbins, Dana; Anderson, Scott; Macbeth, Alyssa; Tzou, Austin; Carneiro, Mauricio O.; Raychowdhury, Raktima; Russ, Carsten; Hacohen, Nir; Lennon, Niall; Nusbaum, Chad; Regev, Aviv; Amit, Ido] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Rai, Kunal; Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. [Garber, Manuel] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Hacohen, Nir] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Gershenwald, Jeffrey E.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Regev, Aviv] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02142 USA. [Amit, Ido] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. RP Chin, L (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. EM lchin@mdanderson.org; aregev@broadinstitute.org; ido.amit@weizmann.ac.il FU Human Frontiers Science Program Career Development Award; ISF Bikura Institutional Research Grant Program; ERC starting Grant [309788]; NHGRI [1P50HG006193-01, U54HG003067]; NIH Pioneer Award [DP1OD003958-01]; Klarman Cell Observatory; NCI [R01 CA93947, U01 CA1411508]; NIH [P50 CA093459]; NIH Ruth L. Kirschstein National Research Service awards for individual Postdoctoral Fellowships FX We thank R. Satija and S. Schwartz for helpful discussions. We thank J. Bochicchio for project management, A. Wysoker for the development of the data transfer pipeline and the Broad's Genomics Platform for sequencing. We also thank T. L. Calderone for preparing and sending the melanoma tumours. We thank L. Gaffney for production of the graphical abstract. This work was supported by the Human Frontiers Science Program Career Development Award (I. A.), the ISF Bikura Institutional Research Grant Program (I. A.), ERC starting Grant 309788 (I. A.), NHGRI (1P50HG006193-01 to I. A. and A. R.), NIH Pioneer Award (DP1OD003958-01 to A. R.), Klarman Cell Observatory (A. R.), NCI (R01 CA93947 to L. C.), NCI (U01 CA1411508 to L. C.), NHGRI (U54HG003067 to C. R.), NIH (P50 CA093459 to J. G.) and NIH Ruth L. Kirschstein National Research Service awards for individual Postdoctoral Fellowships (C.S.C.). NR 30 TC 5 Z9 5 U1 1 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD OCT PY 2013 VL 4 AR 2672 DI 10.1038/ncomms3672 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 245OP UT WOS:000326473500004 PM 24157732 ER PT J AU Sethi, DK Gordo, S Schubert, DA Wucherpfennig, KW AF Sethi, Dhruv K. Gordo, Susana Schubert, David A. Wucherpfennig, Kai W. TI Crossreactivity of a human autoimmune TCR is dominated by a single TCR loop SO NATURE COMMUNICATIONS LA English DT Article ID T-CELL-RECEPTOR; MYELIN BASIC-PROTEIN; MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-II MOLECULE; MULTIPLE-SCLEROSIS; PEPTIDE-MHC; STRUCTURAL BASIS; SELF-PEPTIDE; CRYSTAL-STRUCTURE; RECOGNITION AB Self-reactive CD4 T cells are thought to have a central role in the pathogenesis of many chronic inflammatory human diseases. Microbial peptides can activate self-reactive T cells, but the structural basis for such crossreactivity is not well understood. The Hy.1B11 T cell receptor (TCR) originates from a patient with multiple sclerosis and recognizes the self-antigen myelin basic protein. Here we report the structural mechanism of TCR crossreactivity with two distinct peptides from human pathogens. The structures show that a single TCR residue (CDR3 alpha F95) makes the majority of contacts with the self-peptide and both microbial peptides (66.7-80.6%) due to a highly tilted TCR-binding topology on the peptide-MHC surface. Further, a neighbouring residue located on the same TCR loop (CDR3 alpha E98) forms an energetically critical interaction with the MHC molecule. These data show how binding by a self-reactive TCR favors crossreactivity between self and microbial antigens. C1 [Sethi, Dhruv K.; Gordo, Susana; Schubert, David A.; Wucherpfennig, Kai W.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM kai_wucherpfennig@dfci.harvard.edu FU NIH [PO1 AI045757, RO1 AI064177]; National Multiple Sclerosis Society; Cancer Research Institute; National Center for Research Resources [5P41RR015301-10]; National Institute of General Medical Sciences from the National Institutes of Health [8P41 GM103403-10]; U.S. DOE [DE-AC02-06CH11357] FX This work was supported by grants from the NIH (PO1 AI045757 and RO1 AI064177 to K. W. W.) and postdoctoral fellowships from the National Multiple Sclerosis Society (to D. K. S. and S. G.) and the Cancer Research Institute (to D. A. S.). Diffraction data were collected at the Advanced Photon Source using beamlines allocated to the Northeastern Collaborative Access Team. These beamlines are supported by grants from the National Center for Research Resources (5P41RR015301-10) and the National Institute of General Medical Sciences (8P41 GM103403-10) from the National Institutes of Health. Use of the Advanced Photon Source, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the U.S. DOE under Contract No. DE-AC02-06CH11357. NR 58 TC 9 Z9 9 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD OCT PY 2013 VL 4 AR 2623 DI 10.1038/ncomms3623 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 245OE UT WOS:000326472200012 PM 24136005 ER PT J AU Koch, R Demant, M Guntsch, A Cicholas, A Aung, T Venkataramani, V Diering, N Wenzel, D Chapuy, B Trumper, L Wulf, G AF Koch, R. Demant, M. Guentsch, A. Cicholas, A. Aung, T. Venkataramani, V. Diering, N. Wenzel, D. Chapuy, B. Truemper, L. Wulf, G. TI Exosome mediated Wnt-Signaling augments side population in diffuse large B-cell lymphomas SO ONKOLOGIE LA English DT Meeting Abstract C1 [Koch, R.; Demant, M.; Guentsch, A.; Cicholas, A.; Aung, T.; Venkataramani, V.; Diering, N.; Truemper, L.; Wulf, G.] Univ Med, Gottingen, Germany. [Wenzel, D.] Max Planck Inst Biophys Chem, D-37077 Gottingen, Germany. [Chapuy, B.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-584X EI 1423-0240 J9 ONKOLOGIE JI Onkologie PD OCT PY 2013 VL 36 SU 7 BP 134 EP 134 PG 1 GA 244BA UT WOS:000326360900325 ER PT J AU Koch, R Cicholas, A Aung, T Demant, M Venkataramani, V Chapuy, B Trumper, L Wulf, G AF Koch, R. Cicholas, A. Aung, T. Demant, M. Venkataramani, V. Chapuy, B. Truemper, L. Wulf, G. TI SFRP4 inhibits proliferation of DLBCL by antagonizing wnt-signaling SO ONKOLOGIE LA English DT Meeting Abstract C1 [Koch, R.; Cicholas, A.; Aung, T.; Demant, M.; Venkataramani, V.; Truemper, L.; Wulf, G.] Univ Med, Gottingen, Germany. [Chapuy, B.] Dana Farber Canc Inst, 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 0378-584X EI 1423-0240 J9 ONKOLOGIE JI Onkologie PD OCT PY 2013 VL 36 SU 7 BP 134 EP 135 PG 2 GA 244BA UT WOS:000326360900326 ER PT J AU Reichardt, P Demetri, G Kang, YK Blay, JY Joensuu, H Maki, RG Rutkowski, P Hohenberger, P Gelderblom, H Leahy, MG von Mehren, M Schoffski, P Blackstein, ME Le Cesne, A Badalamenti, G Xu, J Nishida, T Kuss, I Casali, PG AF Reichardt, P. Demetri, G. Kang, Y-K Blay, J-Y Joensuu, H. Maki, R. G. Rutkowski, P. Hohenberger, P. Gelderblom, H. Leahy, M. G. von Mehren, M. Schoffski, P. Blackstein, M. E. Le Cesne, A. Badalamenti, G. Xu, J. Nishida, T. Kuss, I Casali, P. G. TI Mutational analysis of plasma DNA from patients (pts) in the phase III GRID study of regorafenib vs placebo in tyrosine kinase inhibitor (TKI)-refractory GIST: Correlating genotype with clinical outcomes SO ONKOLOGIE LA English DT Meeting Abstract C1 [Reichardt, P.] Helios Klinikum Berlin Buch, Klin Interdisziplinare Onkol, Berlin, Germany. [Demetri, G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kang, Y-K] Asan Med Ctr, Seoul, South Korea. [Blay, J-Y] Ctr Leon Berard, F-69373 Lyon, France. [Joensuu, H.] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Maki, R. G.] Mt Sinai Sch Med, New York, NY USA. [Rutkowski, P.] Maria Sklodowska Curie Mem Canc Ctr & Inst, Warsaw, Poland. [Hohenberger, P.] Univ Mannheim, Med Ctr, D-68131 Mannheim, Germany. [Gelderblom, H.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Leahy, M. G.] Christie NHS Trust Fdn, Manchester, Lancs, England. [von Mehren, M.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Schoffski, P.] Univ Ziekenhuis Gasthuisberg, Louvain, Belgium. [Blackstein, M. E.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Le Cesne, A.] Inst Gustav Roussy, Villejuif, France. [Badalamenti, G.] Univ Palermo, Palermo, Italy. [Xu, J.] Acad Mil Med Sci, Affiliated Hosp, Beijing, Peoples R China. [Nishida, T.] Osaka Police Hosp, Osaka, Japan. [Kuss, I] Bayer HealthCare, Berlin, Germany. [Casali, P. G.] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 0 Z9 0 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-584X EI 1423-0240 J9 ONKOLOGIE JI Onkologie PD OCT PY 2013 VL 36 SU 7 BP 179 EP 180 PG 2 GA 244BA UT WOS:000326360900445 ER PT J AU Bauer, S Joensuu, H Casali, P Reichardt, P Kang, YK Blay, JY Rutkowski, P Gelderblom, H Hohenberger, P Leahy, M von Mehren, M Badalamenti, G Blackstein, M Le Cesne, A Schoffski, P Maki, RG Xu, J Nishida, T Kappeler, C Kuss, I Demetri, GD AF Bauer, S. Joensuu, H. Casali, P. Reichardt, P. Kang, Y-K Blay, J-Y Rutkowski, P. Gelderblom, H. Hohenberger, P. Leahy, M. von Mehren, M. Badalamenti, G. Blackstein, M. Le Cesne, A. Schoffski, P. Maki, R. G. Xu, J. Nishida, T. Kappeler, C. Kuss, I Demetri, G. D. TI Results from a phase III trial (GRID) evaluating regorafenib in metastatic gastrointestinal stromal tumour (GIST): Subgroup analysis of outcomes based on pretreatment characteristics SO ONKOLOGIE LA English DT Meeting Abstract C1 [Bauer, S.] Univ Klinikum Essen, Essen, Germany. [Joensuu, H.] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Casali, P.] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Reichardt, P.] Helios Klinikum Berlin Buch, Berlin, Germany. [Kang, Y-K] Asan Med Ctr, Seoul, South Korea. [Blay, J-Y] Ctr Leon Berard, F-69373 Lyon, France. [Rutkowski, P.] Maria Sklodowska Curie Mem Canc Ctr & Inst, Warsaw, Poland. [Gelderblom, H.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Hohenberger, P.] Univ Mannheim, Med Ctr, D-68131 Mannheim, Germany. [Leahy, M.] Christie NHS Trust Fdn, Manchester, Lancs, England. [von Mehren, M.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Badalamenti, G.] Univ Palermo, Palermo, Italy. [Blackstein, M.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Le Cesne, A.] Inst Gustav Roussy, Villejuif, France. [Schoffski, P.] Univ Ziekenhuis Gasthuisberg, Louvain, Belgium. [Maki, R. G.] Mt Sinai Sch Med, New York, NY USA. [Xu, J.] Acad Mil Med Sci, Affiliated Hosp, Beijing, Peoples R China. [Nishida, T.] Osaka Police Hosp, Osaka, Japan. [Kappeler, C.; Kuss, I] Bayer HealthCare, Berlin, Germany. [Demetri, G. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 0 Z9 0 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-584X EI 1423-0240 J9 ONKOLOGIE JI Onkologie PD OCT PY 2013 VL 36 SU 7 BP 180 EP 181 PG 2 GA 244BA UT WOS:000326360900446 ER PT J AU Koch, R Aung, T Vogel, D Menck, K Venkataramani, V Mohring, S Chapuy, B Trumper, L Wulf, G AF Koch, R. Aung, T. Vogel, D. Menck, K. Venkataramani, V. Mohring, S. Chapuy, B. Truemper, L. Wulf, G. TI Association of Exosome Secretion and Drug Resistance in Diffuse Large B-cell Lymphomas SO ONKOLOGIE LA English DT Meeting Abstract C1 [Koch, R.; Aung, T.; Vogel, D.; Menck, K.; Venkataramani, V.; Mohring, S.; Truemper, L.; Wulf, G.] UMG, Gottingen, Germany. [Chapuy, B.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-584X EI 1423-0240 J9 ONKOLOGIE JI Onkologie PD OCT PY 2013 VL 36 SU 7 BP 199 EP 199 PG 1 GA 244BA UT WOS:000326360900494 ER PT J AU Fan, F Tonon, G Bashari, HM Vallet, S Antonini, E Goldschmidt, H Schulze-Bergkamen, H Opferman, J Settler, M Anderson, KC Jager, D Podar, K AF Fan, F. Tonon, G. Bashari, H. M. Vallet, S. Antonini, E. Goldschmidt, H. Schulze-Bergkamen, H. Opferman, J. Settler, M. Anderson, K. C. Jaeger, D. Podar, K. TI Targeting Mcl-1 for multiple myeloma (MM) therapy: Drug-induced generation of Mcl-1 fragment Mcl-1128-350 triggers MM cell death via c-Jun upregulation SO ONKOLOGIE LA English DT Meeting Abstract C1 [Fan, F.; Bashari, H. M.; Vallet, S.; Goldschmidt, H.; Schulze-Bergkamen, H.; Jaeger, D.; Podar, K.] Heidelberg Univ, Natl Ctr Tumor Dis NCT, Heidelberg, Germany. [Fan, F.; Bashari, H. M.; Vallet, S.; Schulze-Bergkamen, H.; Jaeger, D.; Podar, K.] German Canc Res Ctr, Heidelberg, Germany. [Tonon, G.; Antonini, E.] Ist Sci San Raffaele, Div Mol Oncol, Funct Genom Canc Unit, I-20132 Milan, Italy. [Goldschmidt, H.] Heidelberg Univ, German Canc Res Ctr DKFZ, Heidelberg, Germany. [Goldschmidt, H.] Heidelberg Univ, Dept Hematol & Oncol, Heidelberg, Germany. [Opferman, J.] St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA. [Settler, M.; Anderson, K. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-584X EI 1423-0240 J9 ONKOLOGIE JI Onkologie PD OCT PY 2013 VL 36 SU 7 BP 213 EP 213 PG 1 GA 244BA UT WOS:000326360900532 ER PT J AU Niemeyer, E Kamoun, WS Han, HS Huang, Y Bhaumik, J Chen, Y Gillisen, M Martin, JD Roberge, S Lanning, RM Cui, J Munn, LL Nocera, DG Padera, T Fukumura, D Jain, RK Bawendi, MG Dunst, J Duda, DG AF Niemeyer, E. Kamoun, W. S. Han, H. -S. Huang, Y. Bhaumik, J. Chen, Y. Gillisen, M. Martin, J. D. Roberge, S. Lanning, R. M. Cui, J. Munn, L. L. Nocera, D. G. Padera, T. Fukumura, D. Jain, R. K. Bawendi, M. G. Dunst, J. Duda, D. G. TI Multiphoton microscopy and in-situ labeling techniques allow detection of endogenous hematopoetic stem cells and measurement of functional parameters in the stem cell niche SO ONKOLOGIE LA English DT Meeting Abstract C1 [Niemeyer, E.; Dunst, J.] Med Univ Lubeck, Klin Strahlentherapie, D-23538 Lubeck, Germany. [Niemeyer, E.; Kamoun, W. S.; Huang, Y.; Bhaumik, J.; Chen, Y.; Gillisen, M.; Martin, J. D.; Roberge, S.; Lanning, R. M.; Munn, L. L.; Padera, T.; Fukumura, D.; Jain, R. K.; Duda, D. G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Niemeyer, E.; Kamoun, W. S.; Huang, Y.; Bhaumik, J.; Chen, Y.; Gillisen, M.; Martin, J. D.; Roberge, S.; Lanning, R. M.; Munn, L. L.; Padera, T.; Fukumura, D.; Jain, R. K.; Duda, D. G.] Harvard Univ, Sch Med, Boston, MA USA. [Han, H. -S.; Cui, J.; Nocera, D. G.; Bawendi, M. G.] MIT, Dept Chem, Cambridge, MA 02139 USA. RI Munn, Lance/L-3950-2016; Dunst, Juergen/D-2138-2010 OI Munn, Lance/0000-0003-0698-7232; NR 0 TC 0 Z9 0 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-584X EI 1423-0240 J9 ONKOLOGIE JI Onkologie PD OCT PY 2013 VL 36 SU 7 BP 229 EP 230 PG 2 GA 244BA UT WOS:000326360900577 ER PT J AU Garza, JLB Eijckelhof, BHW Huysmans, MA Catalano, PJ Katz, JN Johnson, PW van Dieen, JH van der Beek, AJ Dennerlein, JT AF Garza, Jennifer L. Bruno Eijckelhof, Belinda H. W. Huysmans, Maaike A. Catalano, Paul J. Katz, Jeffrey N. Johnson, Peter W. van Dieen, Jaap H. van der Beek, Allard J. Dennerlein, Jack T. TI The effect of over-commitment and reward on trapezius muscle activity and shoulder, head, neck, and torso postures during computer use in the field SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE psychosocial; VDT; MSDs; exposure assessment; office ergonomics ID UPPER-LIMB SYMPTOMS; MUSCULOSKELETAL SYMPTOMS; OCCUPATIONAL-HEALTH; OFFICE WORKERS; RISK-FACTORS; DISORDERS; EXPOSURE; PATHOPHYSIOLOGY; INTERVENTIONS; VARIABILITY AB Background Because of reported associations of psychosocial factors and computer related musculoskeletal symptoms, we investigated the effects of a workplace psychosocial factor, reward, in the presence of over-commitment, on trapezius muscle activity and shoulder, head, neck, and torso postures during computer use. Methods We measured 120 office workers across four groups (lowest/highest reward/over-commitment), performing their own computer work at their own workstations over a 2-hr period. Results Median trapezius muscle activity (P=0.04) and median neck flexion (P=0.03) were largest for participants reporting simultaneously low reward and high over-commitment. No differences were observed for other muscle activities or postures. Conclusions These data suggest that the interaction of reward and over-commitment can affect upper extremity muscle activity and postures during computer use in the real work environment. This finding aligns with the hypothesized biomechanical pathway connecting workplace psychosocial factors and musculoskeletal symptoms of the neck and shoulder. Am. J. Ind. Med. 56:1190-1200, 2013. (c) 2013 Wiley Periodicals, Inc. C1 [Garza, Jennifer L. Bruno; Katz, Jeffrey N.; Dennerlein, Jack T.] Harvard Univ, Dept Environm Hlth, Boston, MA 02115 USA. [Eijckelhof, Belinda H. W.; Huysmans, Maaike A.; van der Beek, Allard J.] Vrije Univ Amsterdam, Med Ctr, Dept Publ & Occupat Hlth, Amsterdam, Netherlands. [Eijckelhof, Belinda H. W.; Huysmans, Maaike A.; van Dieen, Jaap H.; van der Beek, Allard J.; Dennerlein, Jack T.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [Eijckelhof, Belinda H. W.; Huysmans, Maaike A.; van der Beek, Allard J.] TNO VU VUmc, Body Work Res Ctr Phys Act Work & Hlth, Amsterdam, Netherlands. [Catalano, Paul J.] Harvard Univ, Cambridge, MA 02138 USA. [Catalano, Paul J.] Dana Farber Canc Inst Boston, Boston, MA USA. [Katz, Jeffrey N.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Katz, Jeffrey N.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Katz, Jeffrey N.] Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Johnson, Peter W.] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. [van Dieen, Jaap H.] Vrije Univ Amsterdam, Fac Human Movement Sci, Res Inst MOVE, Amsterdam, Netherlands. [Dennerlein, Jack T.] Northeastern Univ, Dept Phys Therapy, Boston, MA 02115 USA. RP Dennerlein, JT (reprint author), Northeastern Univ, 6 Robinson Hall Off 308F,360 Huntington Ave, Boston, MA 02115 USA. EM j.dennerlein@neu.edu RI Johnson, Peter/C-3046-2011; OI Johnson, Peter/0000-0001-5583-5919; Dennerlein, Jack/0000-0001-7703-643X; van Dieen, Jaap/0000-0002-7719-5585 FU CDC/NIOSH [RO1-0H-08781] FX This study was funded in part by Grant sponsor: CDC/NIOSH; Grant number: RO1-0H-08781 (PI: Dennerlein). The authors would like to thank Sachin Raina, Patrik Rynell, and Birgette Blatter for their contributions to the design, data collection, and analysis for this study. The authors would like to thank Paul Landsbergis for his assistance and suggestions regarding the definition of over-commitment and the different ways in which over-commitment may affect biomechanical loading. NR 39 TC 8 Z9 8 U1 1 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0271-3586 EI 1097-0274 J9 AM J IND MED JI Am. J. Ind. Med. PD OCT PY 2013 VL 56 IS 10 BP 1190 EP 1200 DI 10.1002/ajim.22192 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 210JT UT WOS:000323829200008 ER PT J AU Mohammad-Taheri, Z Nadji, SA Raisi, F Mohammadi, F Bahadori, M Mark, EJ AF Mohammad-Taheri, Zohreh Nadji, Seyed Alireza Raisi, Farshid Mohammadi, Forouzan Bahadori, Moslem Mark, Eugene Jerome TI No association between simian virus 40 and diffuse malignant mesothelioma of the pleura in Iranian patients: A molecular and epidemiologic case-control study of 60 patients SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE mesothelioma malignant; PCR; simian virus 40; etiology ID LARGE T-ANTIGEN; SV40; DNA; EXPRESSION; CANCER; CELLS; PATHOGENESIS; SEQUENCES; ASBESTOS; VACCINE AB Background Diffuse malignant mesothelioma (DMM) is increasing in incidence on a worldwide basis and is linked to exposure to asbestos. Simian virus 40 (SV40), a DNA virus, was introduced inadvertently to human populations through contaminated polio vaccine during the years 1956-1963. It has been associated with various types of malignancy in animal experiments. There have been suggestions that SV40 might play a role in the pathogenesis of DMM. Objective To evaluate the association between SV40 and DMM in Iranian patients. Method In a case-control study between the years 2007-2008, isolated DNA from 60 paraffin blocks of patients with DMM and 60 controls was assessed to detect three human polyomaviruses (JCV, BKV, and SV40) using three different sets of primers by multiplex nested PCR analysis. We related the patients with diffuse malignant mesotheioma to possible sites of exposure to asbestos. Results None of the DMMs nor any patient in the control group had SV40 genome on polymerase chain reaction (PCR). All of the cases were SV40 T antigen negative. Conclusion This study suggests that DMM is independent of SV40 infection in Iran. Am. J. Ind. Med. 56:1221-1225, 2013. (c) 2013 Wiley Periodicals, Inc. C1 [Mohammad-Taheri, Zohreh; Nadji, Seyed Alireza] Shahid Beheshti Univ Med Sci, Natl Res Inst TB & Lung Dis, Virol Res Ctr, Tehran, Iran. [Raisi, Farshid] Shahid Beheshti Univ Med Sci, Dept Pathol & Lab Med, Masih Daneshvari Hosp, NRITLD, Tehran, Iran. [Mohammadi, Forouzan] Shahid Beheshti Univ Med Sci, Chron Resp Dis Res Ctr, Natl Res Inst TB & Lung Dis, Tehran, Iran. [Bahadori, Moslem] Shahid Beheshti Univ Med Sci, Clin TB & Epidemiol Res Ctr, Natl Res Inst TB & Lung Dis, Tehran, Iran. [Mark, Eugene Jerome] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Mohammad-Taheri, Z (reprint author), Daneshvary Hosp, NRITLD, Tehran, Iran. EM zohrehmt@yahoo.com RI Nadji, Seyed Alireza/C-4172-2016; OI Nadji, Seyed Alireza/0000-0002-8823-384X; Bahadori, Moslem/0000-0001-7050-6320 NR 31 TC 2 Z9 2 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0271-3586 EI 1097-0274 J9 AM J IND MED JI Am. J. Ind. Med. PD OCT PY 2013 VL 56 IS 10 BP 1221 EP 1225 DI 10.1002/ajim.22160 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 210JT UT WOS:000323829200011 PM 23828611 ER PT J AU Ryan, ET AF Ryan, Edward T. TI Eyes on the Prize: Lessons from the Cholera Wars for Modern Scientists, Physicians, and Public Health Officials SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Editorial Material C1 [Ryan, Edward T.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM etryan@partners.org NR 0 TC 1 Z9 1 U1 0 U2 5 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD OCT PY 2013 VL 89 IS 4 BP 610 EP 614 DI 10.4269/ajtmh.13-0173 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 240UB UT WOS:000326122100002 PM 24106185 ER PT J AU Oh, S Go, GW Choi, NJ Oh, S Kim, Y AF Oh, Sangnarn Go, Gwang-woong Choi, Nag-Jin Oh, Sejong Kim, Younghoon TI Possible Involvement of Mycoplasma hominis in Inhibiting the Formation of Biofilms by Uropathogenic Escherichia coli (UPEC) SO BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY LA English DT Article DE biofilm formation; Mycoplasma hominis; uropathogenic Escherichia coli; whole transcriptome analysis ID URINARY-TRACT-INFECTIONS; CELLS; EXOPOLYSACCHARIDE; COMMUNITIES; EXPRESSION; VIRULENCE; STRAINS; O157-H7; INDOLE; CFT073 AB Here we examined the involvement of Mycoplasma hominis in the formation of biofilms by uropathogenic Escherichia coli (UPEC) strain CFT073. Initially, we thought that M. hominis does not affect the fitness of UPEC, including the growth and production of signaling molecules, such as autoinducer-2 and indole. We found, however, that the presence of M. hominis significantly decreased the degree of biofilm formation by UPEC CFT073 (approximately a 60% reduction for 10(5) ccu/mL of M. hominis as compared with UPEC alone). We also found that it had a slight effect in inhibiting the attachment and cytotoxicity of UPEC CFT073. These findings are specific to these UPEC strains rather than to enterohemorrhagic E. coli (EHEC) strains, found in normal intestinal flora. In addition, we performed whole-transcriptome profiling and quantitative realtime polymerase chain reaction (qRT-PCR) analysis. This indicated that the PhoPQ system and the anti-termination protein (encoded by ybcQ) were involved in the reduction of biofilm formation by M. hominis (corroborated by qRT-PCR). Furthermore, our results indicate that M. hominis raises the degree of transcription of toxin genes, including hha and pasT. Hence, we suggest a possible role of M. hominis in affecting the formation of biofilms by UPEC in the urinary tract. C1 [Oh, Sangnarn] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Go, Gwang-woong] Yale Univ, Sch Med, Cardiovasc Res Ctr, New Haven, CT 06511 USA. [Choi, Nag-Jin; Kim, Younghoon] Chonbuk Natl Univ, Dept Anim Sci, Jeonju 561756, South Korea. [Choi, Nag-Jin; Kim, Younghoon] Chonbuk Natl Univ, Inst Rare Earth Biol Applicat, Jeonju 561756, South Korea. [Oh, Sejong] Chonnam Natl Univ, Inst Agr Sci & Technol, Div Anim Sci, Kwangju 500757, South Korea. RP Kim, Y (reprint author), Chonbuk Natl Univ, Dept Anim Sci, Jeonju 561756, South Korea. EM ykeys2584@jbnu.ac.kr FU Cooperative Research Program for Agriculture Science and Technology Development, Rural Development Administration, Republic of Korea [PJ007963] FX We are grateful to Dr. Harry L. Mobley (University of Michigan Medical School) and to Dr. Indal Park (Kosin University College of Medicine) for providing us with the UPEC CFT073 and M. hominis PG21 strains respectively. This work was supported by the Cooperative Research Program for Agriculture Science and Technology Development, Rural Development Administration, Republic of Korea (project no. PJ007963). NR 29 TC 0 Z9 0 U1 0 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0916-8451 EI 1347-6947 J9 BIOSCI BIOTECH BIOCH JI Biosci. Biotechnol. Biochem. PD OCT PY 2013 VL 77 IS 10 BP 2025 EP 2029 DI 10.1271/bbb.130320 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry, Applied; Food Science & Technology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry; Food Science & Technology GA 245TK UT WOS:000326486500008 PM 24096662 ER PT J AU Frankel, HL Kaplan, LJ AF Frankel, Heidi L. Kaplan, Lewis J. TI In brief SO CURRENT PROBLEMS IN SURGERY LA English DT Editorial Material C1 [Frankel, Heidi L.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Kaplan, Lewis J.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Kaplan, Lewis J.] Yale Univ, Sch Med, Sect Trauma Surg Crit Care & Surg Emergencies, New Haven, CT USA. RP Frankel, HL (reprint author), Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0011-3840 EI 1535-6337 J9 CURR PROB SURG JI Curr. Probl. Surg. PD OCT PY 2013 VL 50 IS 10 BP 414 EP 417 DI 10.1067/j.cpsurg.2013.07.002 PG 4 WC Surgery SC Surgery GA 245QQ UT WOS:000326479300002 ER PT J AU Tinti, MS Gracias, VH Kaplan, LJ AF Tinti, Meridith S. Gracias, Vincente H. Kaplan, Lewis J. TI Adjuncts to ventilation part II: Monitoring, fluid management, bundles, and positioning SO CURRENT PROBLEMS IN SURGERY LA English DT Review ID RESPIRATORY-DISTRESS-SYNDROME; RANDOMIZED CONTROLLED-TRIAL; CENTRAL VENOUS CATHETER; ACUTE LUNG INJURY; COMPARTMENT SYNDROME; PULMONARY-ARTERY; FAILURE; PNEUMONIA; THERAPY C1 [Tinti, Meridith S.] UMDNJ Robert Wood Johnson Med Sch, New Brunswick, NJ USA. [Tinti, Meridith S.; Gracias, Vincente H.] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. [Gracias, Vincente H.] UMDNJ Robert Wood Johnson Med Sch, Div Trauma & Acute Care Surg, New Brunswick, NJ USA. [Gracias, Vincente H.] Univ Illinois, Chicago, IL 60680 USA. [Gracias, Vincente H.] Univ Penn, Surg ICU, Philadelphia, PA 19104 USA. [Kaplan, Lewis J.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Kaplan, Lewis J.] Yale Univ, Sch Med, Sect Trauma Surg Crit Care & Surg Emergencies, New Haven, CT USA. RP Tinti, MS (reprint author), UMDNJ Robert Wood Johnson Med Sch, New Brunswick, NJ USA. NR 22 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0011-3840 EI 1535-6337 J9 CURR PROB SURG JI Curr. Probl. Surg. PD OCT PY 2013 VL 50 IS 10 BP 433 EP 437 DI 10.1067/j.cpsurg.2013.08.006 PG 5 WC Surgery SC Surgery GA 245QQ UT WOS:000326479300004 PM 24156840 ER PT J AU Maung, AA Kaplan, LJ AF Maung, Adrian A. Kaplan, Lewis J. TI Waveform analysis during mechanical ventilation SO CURRENT PROBLEMS IN SURGERY LA English DT Review ID RECRUITMENT; PRESSURE C1 [Maung, Adrian A.; Kaplan, Lewis J.] Yale Univ, Sch Med, Sect Trauma Surg Crit Care & Surg Emergencies, New Haven, CT 06520 USA. [Maung, Adrian A.] Univ Maryland, R Adams Cowley Shock Trauma Ctr, College Pk, MD 20742 USA. [Kaplan, Lewis J.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Maung, AA (reprint author), Yale Univ, Sch Med, Sect Trauma Surg Crit Care & Surg Emergencies, New Haven, CT 06520 USA. NR 10 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0011-3840 EI 1535-6337 J9 CURR PROB SURG JI Curr. Probl. Surg. PD OCT PY 2013 VL 50 IS 10 BP 438 EP 446 DI 10.1067/j.cpsurg.2013.08.007 PG 9 WC Surgery SC Surgery GA 245QQ UT WOS:000326479300005 PM 24156841 ER PT J AU Jung, HS Kaplan, LJ Park, PK AF Jung, Hee Soo Kaplan, Lewis J. Park, Pauline K. TI Reviewing the studies of the National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network: Outcomes and clinical findings SO CURRENT PROBLEMS IN SURGERY LA English DT Review ID GAMMA-LINOLENIC ACID; MECHANICALLY VENTILATED PATIENTS; RANDOMIZED CONTROLLED-TRIAL; ACUTE MYOCARDIAL-INFARCTION; PULMONARY-ARTERY CATHETERS; CRITICALLY-ILL PATIENTS; EICOSAPENTAENOIC ACID; CALORIC-INTAKE; SURGICAL PATIENTS; AIRWAY PRESSURE C1 [Jung, Hee Soo] Univ Wisconsin Madison, Madison, WI USA. [Kaplan, Lewis J.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Kaplan, Lewis J.] Yale Univ, Sch Med, Sect Trauma Surg Crit Care & Surg Emergencies, New Haven, CT USA. [Park, Pauline K.] Univ Michigan, Dept Surg, Sect Gen Surg, Ann Arbor, MI 48109 USA. RP Jung, HS (reprint author), Univ Wisconsin Madison, Madison, WI USA. NR 56 TC 0 Z9 0 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0011-3840 EI 1535-6337 J9 CURR PROB SURG JI Curr. Probl. Surg. PD OCT PY 2013 VL 50 IS 10 BP 451 EP 462 DI 10.1067/j.cpsurg.2013.08.009 PG 12 WC Surgery SC Surgery GA 245QQ UT WOS:000326479300007 PM 24156843 ER PT J AU Kaplan, LJ Toevs, CC AF Kaplan, Lewis J. Toevs, Christine C. TI Weaning from mechanical ventilation SO CURRENT PROBLEMS IN SURGERY LA English DT Review ID SPONTANEOUS-BREATHING TRIAL; EXTUBATION FAILURE; INDEX; METAANALYSIS; LIBERATION; SEDATION; PROTOCOL; PREDICT; TRAUMA C1 [Kaplan, Lewis J.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Kaplan, Lewis J.] Yale Univ, Sch Med, Sect Trauma Surg Crit Care & Surg Emergencies, New Haven, CT USA. [Toevs, Christine C.] E Carolina Univ, Sch Med, Greenville, NC 27858 USA. RP Kaplan, LJ (reprint author), Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 22 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0011-3840 EI 1535-6337 J9 CURR PROB SURG JI Curr. Probl. Surg. PD OCT PY 2013 VL 50 IS 10 BP 489 EP 494 DI 10.1067/j.cpsurg.2013.08.014 PG 6 WC Surgery SC Surgery GA 245QQ UT WOS:000326479300012 PM 24156848 ER PT J AU Loftis, JM Hauser, P AF Loftis, Jennifer M. Hauser, Peter TI Pain and Opioid Use in Chronic Liver Disease: Optimal Treatment Must Address the Mental Health Care Needs of the Patient SO DIGESTIVE DISEASES AND SCIENCES LA English DT Editorial Material ID SUBSTANCE USE DISORDERS; CHRONIC HEPATITIS-C; PSYCHIATRIC-DISORDERS; DEPRESSED-PATIENTS; VETERANS; INFECTION C1 [Loftis, Jennifer M.] Portland VA Med Ctr, Res & Dev Serv, Portland, OR 97239 USA. [Loftis, Jennifer M.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. [Hauser, Peter] VISN 22 Network Off, Long Beach, CA 90802 USA. RP Hauser, P (reprint author), VISN 22 Network Off, 300 Oceangate,Suite 700, Long Beach, CA 90802 USA. EM Peter.Hauser2@va.gov FU BLRD VA [I01 BX002061]; NIDA NIH HHS [P50 DA018165] NR 21 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 2013 VL 58 IS 10 BP 2753 EP 2755 DI 10.1007/s10620-013-2809-4 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 223BO UT WOS:000324778900044 PM 23959213 ER PT J AU Sonnenberg, A Genta, RM AF Sonnenberg, Amnon Genta, Robert M. TI Lymphocytic and Collagenous Colitis: Epidemiologic Differences and Similarities SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Adenomatous polyps; Collagenous colitis; Geographic distribution; Epidemiology; Lymphocytic colitis; Microscopic colitis ID MICROSCOPIC COLITIS; DISORDERS; DISEASE AB Background It is unknown whether the subtypes of microscopic colitis (MC) represent distinct nosologic entities or related presentations of the same disease. Our aim was to search for epidemiologic differences among its various histopathologic subtypes. Methods In a computerized database of 789,568 colon pathology reports, we compared the characteristics of 8,745 MC patients with those of the remaining population. Results MC was diagnosed as three distinct histopathologic subtypes: lymphocytic colitis (LC) in 51 %, collagenous colitis (CC) in 43 %, and incomplete colitis (IC) in 6 % of patients. Only 0.65 % was simultaneously diagnosed with more than one subtype of MC. The prevalence of all three subtypes showed an age-dependent rise, with the average age (SD) being 63.3 (14.3) years in LC, 66.4 (12.1) years in CC, and 67.3 (12.7) years in IC (p < 0.0001). There was a striking female predominance in all three subtypes, the female fraction being 72 % in LC, 82 % in CC, and 79 % in IC (p < 0.0001). All three subtypes showed similar geographic distributions among different US states. They were similarly associated with diarrhea and weight loss, the odds ratios for all MC being 45.92 (43.35-48.63) and 5.12 (4.68-5.60), respectively, compared to control patients without MC. All three subtypes also harbored significantly less colonic adenomas, the overall odds ratio being 0.11 (0.10-0.12). Conclusion MC comes in three distinct histopathologic entities, which show striking similarities of their general epidemiologic features. The slight differences in their demographic characteristics could point at varying sets of environmental influences that affect the occurrence of subtypes. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Dept Gastroenterol, Portland, OR 97239 USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Genta, Robert M.] Miraca Life Sci, Irving, TX USA. [Genta, Robert M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Genta, Robert M.] Dallas VA Med Ctr, Dallas, TX USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, Dept Gastroenterol, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu FU Takeda Pharmaceuticals FX Amnon Sonnenberg was supported by a grant from Takeda Pharmaceuticals. No funding was obtained for this study. NR 14 TC 11 Z9 11 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 2013 VL 58 IS 10 BP 2970 EP 2975 DI 10.1007/s10620-013-2718-6 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 223BO UT WOS:000324778900010 PM 23709158 ER PT J AU Schafer, CM Campbell, NG Cai, GQ Yu, F Makarov, V Yoon, S Daly, MJ Gibbs, RA Schellenberg, GD Devlin, B Sutcliffe, JS Buxbaum, JD Roeder, K AF Schafer, Chad M. Campbell, Nicholas G. Cai, Guiqing Yu, Fei Makarov, Vladimir Yoon, Seungtai Daly, Mark J. Gibbs, Richard A. Schellenberg, Gerard D. Devlin, Bernie Sutcliffe, James S. Buxbaum, Joseph D. Roeder, Kathryn TI Whole exome sequencing reveals minimal differences between cell line and whole blood derived DNA SO GENOMICS LA English DT Article DE Graphical diagnostics; Lymphoblastoid cell line; Mosaicism; Sequence variant call; Strand bias; Somatic mutation ID DE-NOVO MUTATIONS; COPY NUMBER; GENOME; DISORDERS; FRAMEWORK; NETWORK; RATES AB Two common sources of DNA for whole exome sequencing (WES) are whole blood (WB) and immortalized lymphoblastoid cell line (LCL). However, it is possible that LCLs have a substantially higher rate of mutation than WB, causing concern for their use in sequencing studies. We compared results from paired WB and LCL DNA samples for 16 subjects, using LCLs of low passage number (<5). Using a standard analysis pipeline we detected a large number of discordant genotype calls (approximately 50 per subject) that we segregated into categories of "confidence" based on read-level quality metrics. From these categories and validation by Sanger sequencing, we estimate that the vast majority of the candidate differences were false positives and that our categories were effective in predicting valid sequence differences, including LCLs with putative mosaicism for the non-reference allele (3-4 per exome). These results validate the use of DNA from LCLs of low passage number for exome sequencing. (C) 2013 Elsevier Inc. All rights reserved. C1 [Schafer, Chad M.; Yu, Fei; Roeder, Kathryn] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. [Campbell, Nicholas G.; Sutcliffe, James S.] Vanderbilt Univ, Vanderbilt Brain Inst, Dept Mol Physiol & Biophys, Nashville, IN 37232 USA. [Cai, Guiqing; Makarov, Vladimir; Yoon, Seungtai; Buxbaum, Joseph D.] Mt Sinai, Seaver Autism Ctr Res & Treatment, Icahn Sch Med, New York, NY 10029 USA. [Cai, Guiqing; Makarov, Vladimir; Yoon, Seungtai; Buxbaum, Joseph D.] Mt Sinai, Dept Psychiat, Icahn Sch Med, New York, NY 10029 USA. [Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Dept Med, Boston, MA 02114 USA. [Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Daly, Mark J.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Schellenberg, Gerard D.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Buxbaum, Joseph D.] Mt Sinai, Dept Genet & Genom Sci, Icahn Sch Med, New York, NY 10029 USA. [Buxbaum, Joseph D.] Mt Sinai, Friedman Brain Inst, Icahn Sch Med, New York, NY 10029 USA. [Roeder, Kathryn] Carnegie Mellon Univ, Ray & Stephanie Lane Ctr Computat Biol, Pittsburgh, PA 15213 USA. [Campbell, Nicholas G.; Sutcliffe, James S.] Vanderbilt Univ, Vanderbilt Brain Inst, Dept Psychiatiy, Nashville, TN 37232 USA. RP Roeder, K (reprint author), Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. EM roeder@stat.cmu.edu RI Sutcliffe, James/C-1348-2012; OI Sutcliffe, James/0000-0001-5200-6007; Buxbaum, Joseph/0000-0001-8898-8313 FU ARRA Autism Sequencing Consortium [R01MH089208, R01MH089025, R01MH089004, R01MH089175, R01 MH089482]; NIH [RO1 MH057881, R01 MH061009]; Seaver Foundation; NIH NCRR [UL1 RR024975]; Vanderbilt Kennedy Center for Research on Human Development [P30 HD015052] FX This work was directly supported by the ARRA Autism Sequencing Consortium grants (R01MH089208, R01MH089025-J.D.B., R01MH089004, R01MH089175 and R01 MH089482-J.S.S.), and supported in part by NIH grants RO1 MH057881 (B.D.) and R01 MH061009 (J.S.S.). J.D.B. is supported by the Seaver Foundation. We thank T. Lehner, A. Felsenfeld and P. Bender for their support and contribution to the project. We acknowledge the assistance of M. Potter, A. McGrew and G. Crockett without whom these studies would not be possible, and the Center for Human Genetics Research resources: Computational Genomics Core, Genetic Studies Ascertainment Core and DNA Resources Core, supported in part by NIH NCRR grant UL1 RR024975, and the Vanderbilt Kennedy Center for Research on Human Development (P30 HD015052). We acknowledge the clinicians and organizations that contributed to samples used in this study and particularly the support of families and clinicians of the Icahn School of Medicine at Mount Sinai and Vanderbilt University. M.J.D., R.A.G., G.D.S., B.D., J.S.S., J.D.B. and K.R., are lead investigators in the Autism Sequencing Consortium (ASC). NR 15 TC 4 Z9 4 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD OCT PY 2013 VL 102 IS 4 BP 270 EP 277 DI 10.1016/j.ygeno.2013.05.005 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 244YE UT WOS:000326425300013 PM 23743231 ER PT J AU Vegh, EM Sood, N Singh, JP AF Vegh, Eszter M. Sood, Nitesh Singh, Jagmeet P. TI The Role of Ablation of the Atrioventricular Junction in Patients with Heart Failure and Atrial Fibrillation SO HEART FAILURE CLINICS LA English DT Article DE AV junction ablation; Cardiac resynchronization therapy; Therapy refractory atrial fibrillation ID CARDIAC RESYNCHRONIZATION THERAPY; VENTRICULAR SYSTOLIC DYSFUNCTION; RADIOFREQUENCY CATHETER ABLATION; AV NODAL ABLATION; TACHYCARDIA-INDUCED CARDIOMYOPATHY; CARDIOVERTER-DEFIBRILLATOR SHOCKS; LONG-TERM SURVIVAL; RHYTHM CONTROL; INTRAMURAL DYSSYNCHRONY; MYOCARDIAL-INFARCTION AB Ablation of the atrioventricular junction (AVJ) is a technically easy procedure that is safe and has a high success rate as an intervention for effective ventricular rate control in patients in symptomatic atrial fibrillation. AVJ ablation has been reported to improve quality of life, left ventricular ejection fraction, and exercise duration in these patients and minimize the incidence of inappropriate shocks. Because right ventricular pacing after AVJ ablation may result in decrease in left ventricular function and worsening of heart failure symptoms, there is increasing evidence to support the effectiveness of cardiac resynchronization therapy in atrial fibrillation populations. C1 [Vegh, Eszter M.; Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Sood, Nitesh] Tufts Univ, Lahey Clin, Div Cardiol, Burlington, MA 01805 USA. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, 55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org FU Biotronik; Boston Scientific; Medtronic; Sorin Group; St. Jude Medical FX EMV and NS have no disclosures. JPS: Lectures, consulting and research grants from Biotronik, Boston Scientific, Medtronic, Sorin Group, and St. Jude Medical. NR 78 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7136 J9 HEART FAIL CLIN JI Heart Fail. Clin. PD OCT PY 2013 VL 9 IS 4 BP 489 EP + DI 10.1016/j.hfc.2013.07.003 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 241XS UT WOS:000326202600013 PM 24054481 ER PT J AU Wagner, AJ AF Wagner, Andrew J. TI Sarcoma Preface SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Wagner, AJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM andrew_wagner@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2013 VL 27 IS 5 BP XI EP XII DI 10.1016/j.hoc.2013.08.001 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 244CL UT WOS:000326364600001 PM 24093177 ER PT J AU Barnett, CM Corless, CL Heinrich, MC AF Barnett, Christine M. Corless, Christopher L. Heinrich, Michael C. TI Gastrointestinal Stromal Tumors Molecular Markers and Genetic Subtypes SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE GIST; KIT; PDGFRA; RTK-wild-type; SDH ID SUCCINATE-DEHYDROGENASE SUBUNIT; RECEPTOR TYROSINE KINASE; OF-FUNCTION MUTATIONS; C-KIT; PDGFRA MUTATIONS; SDHA MUTATIONS; INTERSTITIAL-CELLS; CARNEY-STRATAKIS; STRUCTURAL BASIS; BRAF MUTATIONS AB Mutation-activated signaling from the KIT and PDGFRA kinases has been successfully targeted in gastrointestinal stromal tumors (GISTs), with subtle differences between the mutations serving to refine prognosis and more precisely tailor therapy. There is a growing understanding of the molecular drivers of GISTs lacking mutations in KIT or PDGFRA, so called wild-type GISTs, further aiding in management decisions. This article provides an overview of all the known molecular subtypes of GIST and provides information about clinical correlates, treatment, and prognosis depending on the subtype. C1 [Barnett, Christine M.] Oregon Hlth & Sci Univ, OHSU Knight Canc Inst, Div Hematol Oncol, Portland VA Med Ctr, Portland, OR 97239 USA. [Corless, Christopher L.] Oregon Hlth & Sci Univ, OHSU Knight Canc Inst, Dept Pathol, Portland, OR 97239 USA. [Heinrich, Michael C.] Oregon Hlth & Sci Univ, OHSU Knight Canc Inst, Div Hematol Oncol, Portland VA Med Ctr,Dept Med, Portland, OR 97239 USA. [Heinrich, Michael C.] Oregon Hlth & Sci Univ, OHSU Knight Canc Inst, Div Hematol Oncol, Dept Cell & Dev Biol,Portland VA Med Ctr, Portland, OR 97239 USA. RP Heinrich, MC (reprint author), Oregon Hlth & Sci Univ, OHSU Knight Canc Inst, Div Hematol Oncol, Dept Cell & Dev Biol,Portland VA Med Ctr, R&D-19 3710,US Vet Hosp Rd, Portland, OR 97239 USA. EM heinrich@ohsu.edu FU Novartis; Pfizer; Bayer; Ariad; MolecularMD; AROG; Imclone FX None (C.M. Barnett); honoraria from Novartis; consulting fees from Novartis and Pfizer; research support from Novartis, Pfizer, and Bayer (C.L. Corless); honoraria from Onyx; consulting fees from Novartis, Pfizer, Ariad, MolecularMD; research support from Novartis, Pfizer, AROG, Ariad, Imclone; equity interest: MolecularMD (M.C. Heinrich). NR 78 TC 13 Z9 13 U1 1 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2013 VL 27 IS 5 BP 871 EP 888 DI 10.1016/j.hoc.2013.07.003 PG 18 WC Oncology; Hematology SC Oncology; Hematology GA 244CL UT WOS:000326364600002 PM 24093165 ER PT J AU Gronchi, A Raut, CP AF Gronchi, Alessandro Raut, Chandrajit P. TI Treatment of Localized Sarcomas SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Sarcoma; GIST; Surgery; Radiation therapy; Chemotherapy; Tyrosine kinase inhibitors; Survival; Outcome ID SOFT-TISSUE SARCOMAS; GASTROINTESTINAL STROMAL TUMORS; RADIATION-ASSOCIATED ANGIOSARCOMA; ISOLATED LIMB PERFUSION; LONG-TERM OUTCOMES; SINGLE INSTITUTION; PROGNOSTIC-FACTORS; RETROPERITONEAL SARCOMAS; PREOPERATIVE RADIATION; ADJUVANT CHEMOTHERAPY AB Surgery remains the only potentially curative therapy in the management of localized adult soft tissue sarcomas and gastrointestinal stromal tumors. There are over 50 different unique histologic types of soft tissue sarcomas, With different patterns of recurrence and prognosis. Surgical principles and sensitivity to locoregional and systemic treatments vary considerably based on the histologic type and anatomic location, as discussed in detail in this review. C1 [Gronchi, Alessandro] Fdn IRCCS Ist Nazl Tumori, Dept Surg, Sarcoma Serv, I-20133 Milan, Italy. [Raut, Chandrajit P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Surg,Brigham & Womens Hosp,Ctr Sarcoma & Bon, Boston, MA 02115 USA. RP Raut, CP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Surg,Brigham & Womens Hosp,Ctr Sarcoma & Bon, 75 Francis St, Boston, MA 02115 USA. EM craut@partners.org OI Gronchi, Alessandro/0000-0002-4703-3534 NR 62 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2013 VL 27 IS 5 BP 921 EP 938 DI 10.1016/j.hoc.2013.07.006 PG 18 WC Oncology; Hematology SC Oncology; Hematology GA 244CL UT WOS:000326364600005 PM 24093168 ER PT J AU Serrano, C George, S AF Serrano, Cesar George, Suzanne TI Leiomyosarcoma SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Leiomyosarcoma; Chemotherapy; Targeted therapy; Prognostic factors; Uterine leiomyosarcoma ID SOFT-TISSUE SARCOMAS; PHASE-II TRIAL; GYNECOLOGIC-ONCOLOGY-GROUP; INFERIOR VENA-CAVA; GEMCITABINE PLUS DOCETAXEL; FIXED-DOSE-RATE; UTERINE-SARCOMAS; PROGNOSTIC-FACTORS; EUROPEAN ORGANIZATION; RADIATION-THERAPY AB This article presents an overview of the current literature about the biology, pathology, and the clinical management of leiomyosarcoma. In addition, the article emphasizes and discusses the current systemic treatment options available for patients with leiomyosarcoma, which range from cytotoxic chemotherapy to target therapies. Particular leiomyosarcoma subtypes, such as uterine leiomyosarcoma and inferior vena cava leiomyosarcoma, are discussed separately. C1 [Serrano, Cesar] Brigham & Womens Hosp, Fletcher Lab, Dept Pathol, Boston, MA 02115 USA. [Serrano, Cesar; George, Suzanne] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02215 USA. RP George, S (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM sgeorge2@partners.org FU Spanish Society of Medical Oncology; Driscoll Family Leiomyosarcoma Research Fund FX Spanish Society of Medical Oncology (SEOM) Translational Award (C. Serrano); Driscoll Family Leiomyosarcoma Research Fund (S. George). NR 101 TC 13 Z9 15 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2013 VL 27 IS 5 BP 957 EP 974 DI 10.1016/j.hoc.2013.07.002 PG 18 WC Oncology; Hematology SC Oncology; Hematology GA 244CL UT WOS:000326364600007 PM 24093170 ER PT J AU Cote, GM Choy, E AF Cote, Gregory M. Choy, Edwin TI Update in Treatment and Targets in Ewing Sarcoma SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Ewing sarcoma; Chemotherapy; Oncology; Treatment; Tumor ID CHILDRENS-ONCOLOGY-GROUP; PRIMITIVE NEUROECTODERMAL TUMOR; GROUP PHASE-II; MONOCLONAL-ANTIBODY; CANCER GROUP; NEOADJUVANT CHEMOTHERAPY; STANDARD CHEMOTHERAPY; TRANSCRIPTION FACTOR; MULTIMODAL THERAPY; RECURRENT SARCOMAS AB The improvement in outcome for patients with localized and metastatic Ewing sarcoma since the development of cytotoxic chemotherapy remains one of the most profound advances in oncology and one of the proudest achievements of sarcoma researchers. Identification of molecular targets for new treatments has become an intense area within Ewing sarcoma research. The development of improved preclinical Ewing sarcoma models and advanced molecular techniques will build on knowledge of EWS/FLI1 function, EWS/FLI1 transcription targets, and the other critical driver events in these tumors. C1 [Cote, Gregory M.; Choy, Edwin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. RP Choy, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, 32 Fruit St, Boston, MA 02114 USA. EM echoy@partners.org OI Cote, Gregory/0000-0003-0181-886X NR 58 TC 2 Z9 2 U1 0 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2013 VL 27 IS 5 BP 1007 EP 1019 DI 10.1016/j.hoc.2013.07.001 PG 13 WC Oncology; Hematology SC Oncology; Hematology GA 244CL UT WOS:000326364600010 PM 24093173 ER PT J AU Galka, A Wong, KKF Stephani, U Ozaki, T Siniatchkin, M AF Galka, Andreas Wong, Kevin K. F. Stephani, Ulrich Ozaki, Tohru Siniatchkin, Michael TI BLIND SIGNAL SEPARATION OF MIXTURES OF CHAOTIC PROCESSES: A COMPARISON BETWEEN INDEPENDENT COMPONENT ANALYSIS AND STATE SPACE MODELING SO INTERNATIONAL JOURNAL OF BIFURCATION AND CHAOS LA English DT Article DE Blind signal separation; independent component analysis; state space modeling ID NONSTATIONARY TIME-SERIES; LEAST-SQUARES ESTIMATION; MAXIMUM-LIKELIHOOD; DYNAMIC FACTOR; EEG; DECOMPOSITION; ALGORITHM; SYSTEMS; DECONVOLUTION; INFORMATION AB We perform a systematic comparison between different algorithms for solving the Blind Signal Separation problem. In particular, we compare five well-known algorithms for Independent Component Analysis (ICA) with a recently proposed algorithm based on linear state space modeling (IC-LSS). The comparison is based on simulated mixtures of six source signals, five of which are generated by nonlinear deterministic processes evolving on chaotic attractors. The quality of the reconstructed sources is quantified by two measures, one based on a distance measure implemented by a Frobenius norm, and one based on residual mutual information. We find that the IC-LSS modeling algorithm offers several advantages over the ICA algorithms: it succeeds in unmixing Gaussian sources, on short time series it performs, on average, better than static ICA algorithms, it does not try to remove coincidental dependencies resulting from finite data set size, and it shows the potential to reconstruct the sources even in the case of noninvertible mixing. As expected, for the case of non-Gaussian sources, invertible mixing and sufficient time series length, the ICA algorithms typically outperform IC-LSS modeling. C1 [Galka, Andreas; Stephani, Ulrich] Univ Kiel, Dept Neuropediat, D-24098 Kiel, Germany. [Galka, Andreas] Univ Kiel, Inst Expt & Appl Phys, D-24098 Kiel, Germany. [Wong, Kevin K. F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ozaki, Tohru] Tohoku Univ, Aoba Ku, Sendai, Miyagi 9808576, Japan. [Siniatchkin, Michael] Goethe Univ Frankfurt, Dept Psychiat Psychosomat Med & Psychotherapy, D-60528 Frankfurt, Germany. RP Galka, A (reprint author), Univ Kiel, Dept Neuropediat, D-24098 Kiel, Germany. RI Wong, Kin Foon Kevin/C-7896-2014; Stephani, Ulrich/D-1004-2010 FU German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) [Sonderforschungsbereich SFB 855] FX The work of A. Galka was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) through Sonderforschungsbereich SFB 855 "Biomagnetic Sensing". NR 70 TC 2 Z9 2 U1 1 U2 11 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0218-1274 EI 1793-6551 J9 INT J BIFURCAT CHAOS JI Int. J. Bifurcation Chaos PD OCT PY 2013 VL 23 IS 10 AR 1350165 DI 10.1142/S0218127413501654 PG 24 WC Mathematics, Interdisciplinary Applications; Multidisciplinary Sciences SC Mathematics; Science & Technology - Other Topics GA 245MT UT WOS:000326468500003 ER PT J AU Abbasi, SA Ertel, A Shah, RV Dandekar, V Chung, J Bhat, G Desai, AA Kwong, RY Farzaneh-Far, A AF Abbasi, Siddique A. Ertel, Andrew Shah, Ravi V. Dandekar, Vineet Chung, Jaehoon Bhat, Geetha Desai, Ankit A. Kwong, Raymond Y. Farzaneh-Far, Afshin TI Impact of cardiovascular magnetic resonance on management and clinical decision-making in heart failure patients SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article ID NONINVASIVE DETECTION; DISEASE; CARDIOMYOPATHY; DYSFUNCTION; INFARCTION; TRIAL AB Background: Cardiovascular magnetic resonance (CMR) can provide important diagnostic and prognostic information in patients with heart failure. However, in the current health care environment, use of a new imaging modality like CMR requires evidence for direct additive impact on clinical management. We sought to evaluate the impact of CMR on clinical management and diagnosis in patients with heart failure. Methods: We prospectively studied 150 consecutive patients with heart failure and an ejection fraction <= 50% referred for CMR. Definitions for "significant clinical impact" of CMR were pre-defined and collected directly from medical records and/or from patients. Categories of significant clinical impact included: new diagnosis, medication change, hospital admission/discharge, as well as performance or avoidance of invasive procedures (angiography, revascularization, device therapy or biopsy). Results: Overall, CMR had a significant clinical impact in 65% of patients. This included an entirely new diagnosis in 30% of cases and a change in management in 52%. CMR results directly led to angiography in 9% and to the performance of percutaneous coronary intervention in 7%. In a multivariable model that included clinical and imaging parameters, presence of late gadolinium enhancement (LGE) was the only independent predictor of "significant clinical impact" (OR 6.72, 95% CI 2.56-17.60, p=0.0001). Conclusions: CMR made a significant additive clinical impact on management, decision-making and diagnosis in 65% of heart failure patients. This additive impact was seen despite universal use of prior echocardiography in this patient group. The presence of LGE was the best independent predictor of significant clinical impact following CMR. C1 [Abbasi, Siddique A.; Shah, Ravi V.; Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Abbasi, Siddique A.; Shah, Ravi V.] Harvard Univ, Sch Med, Boston, MA USA. [Abbasi, Siddique A.; Ertel, Andrew; Dandekar, Vineet; Chung, Jaehoon; Bhat, Geetha; Desai, Ankit A.; Farzaneh-Far, Afshin] Univ Illinois, Dept Med, Sect Cardiol, Chicago, IL 60612 USA. [Shah, Ravi V.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Bhat, Geetha] Advocate Christ Med Ctr, Ctr Heart Transplant & Assist Devices, Oak Lawn, IL USA. [Farzaneh-Far, Afshin] Univ Illinois, Dept Radiol, Chicago, IL 60612 USA. RP Farzaneh-Far, A (reprint author), Univ Illinois, Dept Med, Sect Cardiol, 840 South Wood St M-C 715,Suite 920 S, Chicago, IL 60612 USA. EM afshin@uic.edu OI Abbasi, Siddique/0000-0002-9601-7565 NR 23 TC 17 Z9 17 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1097-6647 EI 1532-429X J9 J CARDIOVASC MAGN R JI J. Cardiov. Magn. Reson. PD OCT 1 PY 2013 VL 15 AR 89 DI 10.1186/1532-429X-15-89 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 245LX UT WOS:000326466300002 PM 24083836 ER PT J AU Walcott, BP Boehm, KM Stapleton, CJ Mehta, BP Nahed, BV Ogilvy, CS AF Walcott, Brian P. Boehm, Kevin M. Stapleton, Christopher J. Mehta, Brijesh P. Nahed, Brian V. Ogilvy, Christopher S. TI Retrievable stent thrombectomy in the treatment of acute ischemic stroke: Analysis of a revolutionizing treatment technique SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Review DE Endovascular; Ischemia; Neurosurgery; Solitaire; Stent; Stroke; Trevo ID TISSUE-PLASMINOGEN-ACTIVATOR; CEREBRAL-ARTERY OCCLUSION; SINGLE-CENTER EXPERIENCE; RT-PA STROKE; MECHANICAL THROMBECTOMY; ANTERIOR CIRCULATION; FLOW RESTORATION; PENUMBRA SYSTEM; SOLITAIRE STENT; MERCI RETRIEVER AB Acute ischemic stroke resulting from intracranial vessel occlusion is associated with high morbidity and mortality. The mainstays of therapy are fibrinolytics and mechanical thrombectomy in properly selected patients. A new Food and Drug Administration-approved technology to perform thrombectomy, retrievable stenting, may provide superior revascularization rates and improved patient outcomes. We analyzed the cumulative human experience reported for the Trevo Pro Retrieval System (Stryker, Kalamazoo, MI, USA) and the Solitaire FR Revascularization Device (ev3, Irvine, CA, USA) as the definitive treatment for acute ischemic stroke. A literature search was undertaken to identify studies using the retrievable stents published up to September 2012. Nineteen studies identified a total of 576 patients treated with either the Trevo (n = 221) or Solitaire (n = 355) devices. Pooled data analysis identified median baseline National Institutes of Health Stroke Scale scores of 18.5 +/- 0.289 (standard error of the mean) and 17.9 +/- 0.610, and time to recanalization of 53.9 +/- 23.6 minutes and 59.0 +/- 8.0 minutes for the Trevo and Solitaire groups, respectively. Recanalization was variably defined by individual studies, most commonly achieving at least a thrombolysis in cerebral infarction score of 2a-3 or a thrombolysis in myocardial infarction score of 2-3. Revascularization (83%, 82%), mortality (31%, 14%), hemorrhage (8%, 6%), device complications (5%, 6%), and good patient outcomes (51%, 47%) were found with the Trevo and Solitaire devices, respectively. Preliminary analysis reveals excellent clinical outcomes for retrievable stent technology. This may be attributable to both high rates of revascularization with a relatively short time to perfusion restoration. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Walcott, Brian P.; Boehm, Kevin M.; Stapleton, Christopher J.; Nahed, Brian V.; Ogilvy, Christopher S.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Walcott, Brian P.; Boehm, Kevin M.; Stapleton, Christopher J.; Mehta, Brijesh P.; Nahed, Brian V.; Ogilvy, Christopher S.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Boehm, Kevin M.] Yale Univ, New Haven, CT USA. [Mehta, Brijesh P.] Massachusetts Gen Hosp, Dept Intervent Neuroradiol, Boston, MA 02114 USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu FU NINDS NIH HHS [R25 NS065743] NR 38 TC 11 Z9 11 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD OCT PY 2013 VL 20 IS 10 BP 1346 EP 1349 DI 10.1016/j.jocn.2013.03.015 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 244XC UT WOS:000326422500003 PM 23938012 ER PT J AU Freeman, MP Walker, R Laughren, TP Miller, KK Fava, M AF Freeman, Marlene P. Walker, Rosemary Laughren, Thomas P. Miller, Karen K. Fava, Maurizio TI Female Reproductive Life Cycle and Hormones: Methodology to Improve Clinical Trials SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID PREMENSTRUAL-SYNDROME; MENOPAUSAL STATUS; SEX-DIFFERENCES; DEPRESSION; WOMEN; DISORDERS; ESTRADIOL; EFFICACY; STEROIDS; HISTORY C1 [Freeman, Marlene P.] Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Boston, MA 02114 USA. [Walker, Rosemary] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Laughren, Thomas P.] Massachusetts Gen Hosp, Clin Trials Network & Inst, Boston, MA 02114 USA. [Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Freeman, MP (reprint author), Massachusetts Gen Hosp, Ctr Womens Hlth, Simches Res Bldg,Fl 2,185 Cambridge St, Boston, MA 02114 USA. EM mfreeman@partners.org FU NIMH NIH HHS [R34 MH099315] NR 31 TC 1 Z9 1 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 2013 VL 74 IS 10 BP 1018 EP 1021 DI 10.4088/JCP.13com08742 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 243KU UT WOS:000326316100011 PM 24229755 ER PT J AU Fonarow, GC Liang, L Smith, EE Reeves, MJ Saver, JL Xian, Y Hernandez, AF Peterson, ED Schwamm, LH AF Fonarow, Gregg C. Liang, Li Smith, Eric E. Reeves, Mathew J. Saver, Jeffrey L. Xian, Ying Hernandez, Adrian F. Peterson, Eric D. Schwamm, Lee H. CA GWTG-Stroke Steering Comm Investi TI Comparison of Performance Achievement Award Recognition With Primary Stroke Center Certification for Acute Ischemic Stroke Care SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE acute stroke; measures registry; Primary Stroke Center certification ID AMERICAN-HEART-ASSOCIATION; QUALITY-OF-CARE; GUIDELINES-STROKE; CARDIOVASCULAR-RADIOLOGY; ATTACK; RECOMMENDATIONS; ESTABLISHMENT; OUTCOMES; PROGRAM; DISEASE AB Background-Hospital certification and recognition programs represent 2 independent but commonly used systems to distinguish hospitals, yet they have not been directly compared. This study assessed acute ischemic stroke quality of care measure conformity by hospitals receiving Primary Stroke Center (PSC) certification and those receiving the American Heart Association's Get With The Guidelines-Stroke (GWTG-Stroke) Performance Achievement Award (PAA) recognition. Methods and Results-The patient and hospital characteristics as well as performance/quality measures for acute ischemic stroke from 1356 hospitals participating in the GWTG-Stroke Program 2010-2012 were compared. Hospitals were classified as PAA+/PSC+ (hospitals n=410, patients n=169 302), PAA+/PSC- (n=415, n=129 454), PAA-/PSC+ (n=88, n=26 386), and PAA-/PSC- (n=443, n=75 565). A comprehensive set of stroke measures were compared with adjustment for patient and hospital characteristics. Patient characteristics were similar by PAA and PSC status but PAA-/PSC- hospitals were more likely to be smaller and nonteaching. Measure conformity was highest for PAA+/PSC+ and PAA+/PSC- hospitals, intermediate for PAA-/PSC+ hospitals, and lowest for PAA-/PSC- hospitals (all-or-none care measure 91.2%, 91.2%, 84.3%, and 76.9%, respectively). After adjustment for patient and hospital characteristics, PAA+/PSC+, PAA+/PSC-, and PAA-/PSC+ hospitals had 3.15 (95% CIs 2.86 to 3.47); 3.23 (2.93 to 3.56) and 1.72 (1.47 to 2.00), higher odds for providing all indicated stroke performance measures to patients compared with PAA-/PSC- hospitals. Conclusions-While both PSC certification and GWTG-Stroke PAA recognition identified hospitals providing higher conformity with care measures for patients hospitalized with acute ischemic stroke, PAA recognition was a more robust identifier of hospitals with better performance. C1 [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, Div Neurol, Los Angeles, CA USA. [Liang, Li; Xian, Ying; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Ctr, Durham, NC USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB, Canada. [Reeves, Mathew J.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Div Neurol, Boston, MA 02114 USA. RP Fonarow, GC (reprint author), Univ Calif Los Angeles, Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, 10833 LeConte Ave,Room 47-123 CHS, Los Angeles, CA 90095 USA. EM gfonarow@mednet.ucla.edu RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 FU Boeringher-Ingelheim; Merck; Bristol-Myers Squib/Sanofi Pharmaceutical Partnership; Janssen Pharmaceutical Companies of Johnson Johnson; American Heart Association Pharmaceutical Roundtable FX The Get With The Guidelines-Stroke (GWTG-Stroke) program is provided by the American Heart Association/American Stroke Association. GWTG-Stroke has been funded in the past through support from Boeringher-Ingelheim, Merck, Bristol-Myers Squib/Sanofi Pharmaceutical Partnership, Janssen Pharmaceutical Companies of Johnson & Johnson and the American Heart Association Pharmaceutical Roundtable. The industry sponsors did not participate in the design, analysis, manuscript preparation, review, or approval of this manuscript. NR 27 TC 11 Z9 11 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD OCT PY 2013 VL 2 IS 5 AR UNSP e000451 DI 10.1161/JAHA.113.000451 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243UL UT WOS:000326343200014 PM 24125846 ER PT J AU Lubitz, SA Moser, C Sullivan, L Rienstra, M Fontes, JD Villalon, ML Pai, M McManus, DD Schnabel, RB Magnani, JW Yin, XY Levy, D Pencina, MJ Larson, MG Ellinor, PT Benjamin, EJ AF Lubitz, Steven A. Moser, Carlee Sullivan, Lisa Rienstra, Michiel Fontes, Joao D. Villalon, Mark L. Pai, Manju McManus, David D. Schnabel, Renate B. Magnani, Jared W. Yin, Xiaoyan Levy, Daniel Pencina, Michael J. Larson, Martin G. Ellinor, Patrick T. Benjamin, Emelia J. TI Atrial Fibrillation Patterns and Risks of Subsequent Stroke, Heart Failure, or Death in the Community SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE atrial fibrillation; heart failure; mortality; pattern; risk; stroke ID FOLLOW-UP; PROGRESSION; MANAGEMENT; INTERMITTENT; DIAGNOSIS; PROGNOSIS; SURVIVAL; FEATURES; OUTCOMES; COHORT AB Background-Atrial fibrillation (AF) patterns and their relations with long-term prognosis are uncertain, partly because pattern definitions are challenging to implement in longitudinal data sets. We developed a novel AF classification algorithm and examined AF patterns and outcomes in the community. Methods and Results-We characterized AF patterns between 1980 and 2005 among Framingham Heart Study participants who survived >= 1 year after diagnosis. We classified participants based on their pattern within the first 2 years after detection as having AF without recurrence, recurrent AF, or sustained AF. We examined associations between AF patterns and 10-year survival using proportional hazards regression. Among 612 individuals with AF, mean age was 72.5 +/- 10.8 years, and 53% were men. Of these, 478 participants had >= 2 electrocardiograms (median, 3; limits 2 to 23) within 2 years after initial AF and were classified as having AF without 2-year recurrence (n=63, 10%), recurrent AF (n=162, 26%) or sustained AF (n=207, 34%), although some (n=46, 8%) were indeterminate. Of 432 classified participants, 363 died, 75 had strokes, and 110 were diagnosed with heart failure during the next 10 years. Relative to individuals without AF recurrence, the multivariable-adjusted mortality was higher among people with recurrent AF (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.26 to 3.29) and sustained AF (HR, 2.36; 95% CI, 1.49 to 3.75). Conclusions-In our community-based AF sample, only 10% had AF without early-term (2-year) recurrence. Compared with individuals without 2-year AF recurrences, the 10-year prognosis was worse for individuals with either sustained or recurrent AF. Our proposed AF classification algorithm may be applicable in longitudinal datas ets. C1 [Lubitz, Steven A.; Rienstra, Michiel; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Moser, Carlee; Sullivan, Lisa; Pencina, Michael J.; Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Fontes, Joao D.; Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. [Villalon, Mark L.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Rienstra, Michiel] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Fontes, Joao D.; Schnabel, Renate B.; Magnani, Jared W.; Yin, Xiaoyan; Levy, Daniel; Pencina, Michael J.; Larson, Martin G.; Benjamin, Emelia J.] Boston Univ, Framingham, MA USA. [Fontes, Joao D.; Schnabel, Renate B.; Magnani, Jared W.; Yin, Xiaoyan; Levy, Daniel; Pencina, Michael J.; Larson, Martin G.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Pai, Manju] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA. [McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [McManus, David D.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Schnabel, Renate B.] Univ Heart Ctr Hamburg Eppendorf, Dept Gen & Intervent Cardiol, Hamburg, Germany. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD USA. RP Lubitz, SA (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM slubitz@partners.org OI Larson, Martin/0000-0002-9631-1254; Sullivan, Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336; Rienstra, Michiel/0000-0002-2581-070X FU Evans Center for Interdisciplinary Biomedical Research ARC on Atrial Fibrillation at Boston University; AHA [13EIA14220013]; [N01-HC 25195]; [6R01-NS 17950]; [1RC1HL101056]; [1R01HL102214]; [1R01AG028321]; [1RO1HL092577]; [5R21DA027021]; [1RO1HL104156]; [1K24HL105780]; [1K23HL114724]; [U01HL105268]; [KL2RR031981]; [12FTF11350014]; [09FTF2190028] FX This work was funded by N01-HC 25195, 6R01-NS 17950, grants to Dr Benjamin (1RC1HL101056; 1R01HL102214, 1R01AG028321), Drs Benjamin and Ellinor (1RO1HL092577), Dr Ellinor (5R21DA027021, 1RO1HL104156, 1K24HL105780), Dr Lubitz (1K23HL114724), and Dr McManus (U01HL105268, KL2RR031981), and in part by the Evans Center for Interdisciplinary Biomedical Research ARC on Atrial Fibrillation at Boston University (http://www.bumc.bu.edu/evanscenteribr/). Dr Lubitz (12FTF11350014), Dr Magnani (09FTF2190028), and Dr Ellinor (13EIA14220013) were supported by AHA awards. NR 28 TC 9 Z9 9 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD OCT PY 2013 VL 2 IS 5 AR UNSP e000126 DI 10.1161/JAHA.113.000126 PG 18 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243UL UT WOS:000326343200024 PM 24002369 ER PT J AU McCabe, JM Armstrong, EJ Ku, I Kulkarni, A Hoffmayer, KS Bhave, PD Waldo, SW Hsue, P Stein, JC Marcus, GM Kinlay, S Ganz, P AF McCabe, James M. Armstrong, Ehrin J. Ku, Ivy Kulkarni, Ameya Hoffmayer, Kurt S. Bhave, Prashant D. Waldo, Stephen W. Hsue, Priscilla Stein, John C. Marcus, Gregory M. Kinlay, Scott Ganz, Peter TI Physician Accuracy in Interpreting Potential ST-Segment Elevation Myocardial Infarction Electrocardiograms SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE electrocardiogram; myocardial infarction; quality; telemedicine ID DOOR-TO-BALLOON; PERCUTANEOUS CORONARY INTERVENTION; CATHETERIZATION LABORATORY ACTIVATION; CARDIAC-CATHETERIZATION; 12-LEAD ELECTROCARDIOGRAM; EMERGENCY-DEPARTMENT; WIRELESS TECHNOLOGY; TIME; RECOMMENDATIONS; CARDIOLOGIST AB Background-With adoption of telemedicine, physicians are increasingly asked to diagnose ST-segment elevation myocardial infarctions (STEMIs) based on electrocardiograms (ECGs) with minimal associated clinical information. We sought to determine physicians' diagnostic agreement and accuracy when interpreting potential STEMI ECGs. Methods and Results-A cross-sectional survey was performed consisting of 36 deidentified ECGs that had previously resulted in putative STEMI diagnoses. Emergency physicians, cardiologists, and interventional cardiologists participated in the survey. For each ECG, physicians were asked, "based on the ECG above, is there a blocked coronary artery present causing a STEMI?" The reference standard for ascertaining the STEMI diagnosis was subsequent emergent coronary arteriography. Responses were analyzed with generalized estimating equations to account for nested and repeated measures. One hundred twenty-four physicians interpreted a total of 4392 ECGs. Among all physicians, interreader agreement (kappa) for ECG interpretation was 0.33, reflecting poor agreement. The sensitivity to identify "true" STEMIs was 65% (95% CI: 63 to 67) and the specificity was 79% (95% CI: 77 to 81). There was a 6% increase in the odds of accurate ECG interpretation for every 5 years of experience since medical school graduation (OR 1.06, 95% CI: 1.02 to 1.10, P=0.01). After adjusting for experience, there was no significant difference in the odds of accurate interpretation by specialty-Emergency Medicine (reference), General Cardiology (AOR 0.97, 95% CI: 0.79 to 1.2, P=0.80), or Interventional Cardiology physicians (AOR 1.24, 95% CI: 0.93 to 1.7, P=0.15). Conclusions-There is significant physician disagreement in interpreting ECGs with features concerning for STEMI. Such ECGs lack the necessary sensitivity and specificity to act as a suitable "stand-alone" diagnostic test. C1 [McCabe, James M.] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Armstrong, Ehrin J.] Univ Colorado, Div Cardiol, Denver, CO 80202 USA. [Armstrong, Ehrin J.] VA Colorado Healthcare Syst, Denver, CO USA. [Ku, Ivy] Kaiser Permanente, Dept Cardiol, San Francisco, CA USA. [Kulkarni, Ameya] Kaiser Permanante Mid Atlant Med Grp, Div Cardiol, Washington, DC USA. [Hoffmayer, Kurt S.] Univ Wisconsin, Div Cardiol, Madison, WI 53706 USA. [Bhave, Prashant D.] Univ Iowa, Div Cardiol, Iowa City, IA USA. [Waldo, Stephen W.] Massachusetts Gen Hosp, Div Cardiovasc Med, Boston, MA 02114 USA. [Hsue, Priscilla; Ganz, Peter] Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94143 USA. [Marcus, Gregory M.] Univ Calif San Francisco, Div Electrophysiol, San Francisco, CA 94143 USA. [Stein, John C.] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. [Hsue, Priscilla; Ganz, Peter] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Kinlay, Scott] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA USA. [Kinlay, Scott] VA Boston Healthcare Syst, Div Cardiovasc, Boston, MA USA. RP McCabe, JM (reprint author), 1959 NE Pacific St,Box 356422, Seattle, WA 98195 USA. EM mccabe@aya.yale.edu NR 28 TC 6 Z9 6 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD OCT PY 2013 VL 2 IS 5 AR UNSP e000268 DI 10.1161/JAHA.113.000268 PG 47 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243UL UT WOS:000326343200027 PM 24096575 ER PT J AU Kilpatrick, DG Resnick, HS Milanak, ME Miller, MW Keyes, KM Friedman, MJ AF Kilpatrick, Dean G. Resnick, Heidi S. Milanak, Melissa E. Miller, Mark W. Keyes, Katherine M. Friedman, Matthew J. TI National Estimates of Exposure to Traumatic Events and PTSD Prevalence Using DSM-IV and DSM-5 Criteria SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; COMORBIDITY SURVEY REPLICATION; WOMEN; SYMPTOMS; COLLEGE; SAMPLE AB Prevalence of posttraumatic stress disorder (PTSD) defined according to the American Psychiatric Association's Diagnostic and Statistical Manual fifth edition (DSM-5; 2013) and fourth edition (DSM-IV; 1994) was compared in a national sample of U.S. adults (N = 2,953) recruited from an online panel. Exposure to traumatic events, PTSD symptoms, and functional impairment were assessed online using a highly structured, self-administered survey. Traumatic event exposure using DSM-5 criteria was high (89.7%), and exposure to multiple traumatic event types was the norm. PTSD caseness was determined using Same Event (i.e., all symptom criteria met to the same event type) and Composite Event (i.e., symptom criteria met to a combination of event types) definitions. Lifetime, past-12-month, and past 6-month PTSD prevalence using the Same Event definition for DSM-5 was 8.3%, 4.7%, and 3.8% respectively. All 6 DSM-5 prevalence estimates were slightly lower than their DSM-IV counterparts, although only 2 of these differences were statistically significant. DSM-5 PTSD prevalence was higher among women than among men, and prevalence increased with greater traumatic event exposure. Major reasons individuals met DSM-IV criteria, but not DSM-5 criteria were the exclusion of nonaccidental, nonviolent deaths from Criterion A, and the new requirement of at least 1 active avoidance symptom. C1 [Kilpatrick, Dean G.; Resnick, Heidi S.; Milanak, Melissa E.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Miller, Mark W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Miller, Mark W.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Keyes, Katherine M.] Columbia Univ, Dept Epidemiol, New York, NY USA. [Friedman, Matthew J.] Geisel Sch Med Dartmouth, Hanover, NH USA. [Friedman, Matthew J.] Natl Ctr PTSD, White River Jct, VT USA. RP Kilpatrick, DG (reprint author), 67 President St,South Bldg,Suite 200, Charleston, SC 29425 USA. EM kilpatdg@musc.edu RI Miller, Mark/G-7322-2011 OI Miller, Mark/0000-0001-6393-8563 FU CSRD VA [I01 CX000431]; NCATS NIH HHS [UL1 TR000062]; NCRR NIH HHS [UL1 RR029882]; NIDA NIH HHS [R01 DA023099]; NIMH NIH HHS [T32 MH018869] NR 28 TC 105 Z9 105 U1 11 U2 43 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2013 VL 26 IS 5 BP 537 EP 547 DI 10.1002/jts.21848 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 242ZF UT WOS:000326284900002 PM 24151000 ER PT J AU Harb, GC Phelps, AJ Forbes, D Ross, RJ Gehrman, PR Cook, JM AF Harb, Gerlinde C. Phelps, Andrea J. Forbes, David Ross, Richard J. Gehrman, Philip R. Cook, Joan M. TI A Critical Review of the Evidence Base of Imagery Rehearsal for Posttraumatic Nightmares: Pointing the Way for Future Research SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIALS; SEXUAL ASSAULT SURVIVORS; STRESS-DISORDER; CONSORT STATEMENT; CLINICAL-TRIALS; PTSD; VETERANS; INSOMNIA; QUALITY AB In this article, the authors provide information on key characteristics of imagery rehearsal treatment protocols and examine the quality of reporting of randomized controlled and uncontrolled trials of imagery rehearsal for treating posttraumatic nightmares. Using a reliable and valid scale, two independent psychologists rated 16 trials. Most reports provided insufficient information on a range of variables including the definition of treatment delivery (e.g., therapist supervision, treatment fidelity), description of the participant sample, data analysis (e.g., determination of sample size), and treatment assignment (e.g., randomization procedures). Low methodological quality and poor reporting can lead to inflation of estimates of treatment effects and inadequately substantiated conclusions, such as inflated effect sizes in meta-analytic studies. Numerous imagery rehearsal protocols exist, but in some cases are given different names and tested in pilot studies, slowing progression in the field. Randomized controlled trials of imagery rehearsal with credible comparison conditions, examination of predictors of dropout and outcome, as well as dismantling studies of imagery rehearsal treatment components are needed. C1 [Harb, Gerlinde C.; Ross, Richard J.; Gehrman, Philip R.] Philadelphia VA Med Ctr, Behav Hlth Serv, Philadelphia, PA USA. [Phelps, Andrea J.; Forbes, David] Univ Melbourne, Australian Ctr Posttraumat Mental Hlth, Dept Psychiat, Melbourne, Vic, Australia. [Ross, Richard J.; Gehrman, Philip R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Cook, Joan M.] Yale Univ, Sch Med, Dept Psychiat, West Haven, CT 06516 USA. [Cook, Joan M.] Natl Ctr PTSD, West Haven, CT USA. RP Cook, JM (reprint author), Yale Univ, Sch Med, Dept Psychiat, NEPEC 182,950 Campbell Ave, West Haven, CT 06516 USA. EM Joan.Cook@yale.edu NR 46 TC 6 Z9 6 U1 3 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2013 VL 26 IS 5 BP 570 EP 579 DI 10.1002/jts.21854 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 242ZF UT WOS:000326284900008 PM 24114887 ER PT J AU Kachadourian, LK Taft, CT Holowka, DW Woodward, H Marx, BP Burns, A AF Kachadourian, Lorig K. Taft, Casey T. Holowka, Darren W. Woodward, Halley Marx, Brian P. Burns, Anthony TI Maladaptive Dependency Schemas, Posttraumatic Stress Hyperarousal Symptoms, and Intimate Partner Aggression Perpetration SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID PSYCHOMETRIC PROPERTIES; DISORDER SYMPTOMS; DOMESTIC VIOLENCE; QUESTIONNAIRE; BATTERERS; VETERANS; VALIDITY; FORCES; SCALE; PTSD AB This study examined the associations between maladaptive dependency-related schemas, posttraumatic stress disorder (PTSD) hyperarousal symptoms, and intimate-partner psychological and physical aggression in a sample of court-referred men (N = 174) participating in a domestic-abuser-intervention program. The men were largely African American; average age was 33.5years. The extent to which hyperarousal symptoms moderated the association between dependency schemas and aggression was also examined. Maladaptive dependency-related schemas were positively associated with severe psychological, and mild and severe physical aggression perpetration. Hyperarousal symptoms were positively associated with mild and severe psychological aggression, and mild physical aggression perpetration. Multiple regression analyses showed a significant interaction for mild physical aggression: For those with high levels of hyperarousal symptoms, greater endorsement of maladaptive dependency schemas was associated with the perpetration of aggression (B = 0.98, p = .001). For those with low levels of hyperarousal symptoms, there was no association between dependency schemas and aggression (B = 0.04, ns). These findings suggest that focusing on problematic dependency and PTSD-hyperarousal symptoms in domestic-abuser-intervention programs may be helpful, and that examining related variables as possible moderators between dependency schemas and intimate aggression would be a fruitful area for future research. C1 [Kachadourian, Lorig K.; Taft, Casey T.; Holowka, Darren W.; Marx, Brian P.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Kachadourian, Lorig K.; Taft, Casey T.; Holowka, Darren W.; Marx, Brian P.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Woodward, Halley] Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. [Burns, Anthony] Common Purpose Inc, Boston, MA USA. RP Kachadourian, LK (reprint author), VA Connecticut Healthcare Syst 116B 2, Natl Ctr PTSD, 950 Campbell Ave, West Haven, CT 06516 USA. EM lorig.kachadourian@va.gov NR 43 TC 0 Z9 0 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2013 VL 26 IS 5 BP 580 EP 587 DI 10.1002/jts.21850 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 242ZF UT WOS:000326284900009 PM 24030885 ER PT J AU Dekel, S Ein-Dor, T Gordon, KM Rosen, JB Bonanno, GA AF Dekel, Sharon Ein-Dor, Tsachi Gordon, Kathleen M. Rosen, Jeffrey B. Bonanno, George A. TI Cortisol and PTSD Symptoms Among Male and Female High-Exposure 9/11 Survivors SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; METAANALYSIS; RESPONSES; GENDER; ADULTS AB Only a few studies have examined cortisol response to trauma-related stressors in relation to posttraumatic stress disorder (PTSD). We followed a sample of high-exposure survivors of the attacks on September 11, 2001 (9/11; 32 men and 29 women) and examined their cortisol response after recalling the escape from the attack, 7 and 18 months post-9/11. PTSD symptoms and saliva cortisol levels were assessed before and after trauma recollection. Hierarchical regression analyses revealed that PTSD symptoms and male sex predicted increased cortisol response following recollections. For men, elevated cortisol was associated with greater severity of reexperiencing symptoms (p < .001) and lower severity of avoidance symptoms (p < .001). For women, recall-induced cortisol was minimal and unrelated to PTSD symptoms (p = .164 and p = .331, respectively). These findings suggest that augmented cortisol response to trauma-related stressors may be evident in men reporting symptoms of PTSD. Thus, as cortisol abnormalities related to PTSD symptoms appear sex-specific, future research on mechanisms of sex differences in response to trauma is warranted. C1 [Dekel, Sharon] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Dekel, Sharon] Harvard Univ, Sch Med, Charlestown, MA USA. [Dekel, Sharon] Tel Aviv Univ, Bob Shapell Sch Social Work, IL-69978 Tel Aviv, Israel. [Ein-Dor, Tsachi] Interdisciplinary Ctr IDC, Sch Psychol, Herzliyya, Israel. [Gordon, Kathleen M.; Rosen, Jeffrey B.] Univ Delaware, Dept Psychol, Newark, DE USA. [Bonanno, George A.] Columbia Univ Teachers Coll, New York, NY 10027 USA. RP Dekel, S (reprint author), Massachusetts Gen Hosp East, PTSD Res Lab, 120 2nd Ave, Charlestown, MA 02129 USA. EM sharon.dekel@gmail.com NR 18 TC 10 Z9 12 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2013 VL 26 IS 5 BP 621 EP 625 DI 10.1002/jts.21839 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 242ZF UT WOS:000326284900014 PM 24030869 ER PT J AU Sledge, J Graham, WA Westmoreland, S Sejdic, E Miller, A Hoggatt, A Nesathurai, S AF Sledge, J. Graham, W. Andrew Westmoreland, S. Sejdic, E. Miller, A. Hoggatt, A. Nesathurai, S. TI Spinal cord injury models in non human primates: Are lesions created by sharp instruments relevant to human injuries? SO MEDICAL HYPOTHESES LA English DT Letter ID MACACA-FASCICULARIS; MONKEY; CAT AB The worldwide incidence of traumatic spinal cord injury (SCI) is approximated at 180,000 new cases per year. Experiments using nonhuman primates (NHP) are often used to replicate the human condition in order to advance the understanding of SCI and to assist in the development of new treatments. Experimental spinal cord lesions in NHP have been created by a number of methods including blunt trauma, epidural balloons, circumferential cuffs, and dropping a precision weight over the spinal cord. As well, experimental lesions have been created with sharp instruments after opening the dura mater. However, spinal cord lesions that are created with a sharp instrument in NHP experiments may not replicate the clinical and pathological features of human spinal cord injury. Researchers should recognize the challenges associated with making clinical inferences in human SCIs based on NHP experiments that created experimental lesions with a sharp surgical instrument. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Sledge, J.] Lafayette Bone & Joint Clin, Lafayette, LA USA. [Graham, W. Andrew; Nesathurai, S.] McMaster Univ, Div Phys Med & Rehabil, Hamilton, ON L8S 4K1, Canada. [Graham, W. Andrew] St Josephs Healthcare, Hamilton, ON, Canada. [Westmoreland, S.; Sejdic, E.] Univ Pittsburgh, Dept Elect & Comp Engn, Pittsburgh, PA USA. [Miller, A.; Hoggatt, A.] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. [Nesathurai, S.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA USA. [Graham, W. Andrew; Nesathurai, S.] Hamilton Hlth Sci, Dept Phys Med & Rehabil, Hamilton, ON, Canada. RP Graham, WA (reprint author), McMaster Univ, Dept Med, Div Phys Med & Rehabil, 1280 Main St West, Hamilton, ON L8S 4K1, Canada. EM grahaman@hhsc.ca OI Sejdic, Ervin/0000-0003-4987-8298 NR 18 TC 3 Z9 4 U1 0 U2 8 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 EI 1532-2777 J9 MED HYPOTHESES JI Med. Hypotheses PD OCT PY 2013 VL 81 IS 4 BP 747 EP 748 DI 10.1016/j.mehy.2013.07.040 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 243ZO UT WOS:000326357100050 PM 23948598 ER PT J AU Ageta-Ishihara, N Miyata, T Ohshima, C Watanabe, M Sato, Y Hamamura, Y Higashiyama, T Mazitschek, R Bito, H Kinoshita, M AF Ageta-Ishihara, Natsumi Miyata, Takaki Ohshima, Chika Watanabe, Masahiko Sato, Yoshikatsu Hamamura, Yuki Higashiyama, Tetsuya Mazitschek, Ralph Bito, Haruhiko Kinoshita, Makoto TI Septins promote dendrite and axon development by negatively regulating microtubule stability via HDAC6-mediated deacetylation SO NATURE COMMUNICATIONS LA English DT Article ID BINDING PROTEIN; MAMMALIAN SEPTINS; NEUROTRANSMITTER RELEASE; CAENORHABDITIS-ELEGANS; FLUORESCENT PROTEIN; MOUSE MODEL; HDAC6; TUBULIN; NEURONS; GROWTH AB Neurite growth requires two guanine nucleotide-binding protein polymers of tubulins and septins. However, whether and how those cytoskeletal systems are coordinated was unknown. Here we show that the acute knockdown or knockout of the pivotal septin subunit SEPT7 from cerebrocortical neurons impairs their interhemispheric and cerebrospinal axon projections and dendritogenesis in perinatal mice, when the microtubules are severely hyperacetylated. The resulting hyperstabilization and growth retardation of microtubules are demonstrated in vitro. The phenotypic similarity between SEPT7 depletion and the pharmacological inhibition of a-tubulin deacetylase HDAC6 reveals that HDAC6 requires SEPT7 not for its enzymatic activity, but to associate with acetylated a-tubulin. These and other findings indicate that septins provide a physical scaffold for HDAC6 to achieve efficient microtubule deacetylation, thereby negatively regulating microtubule stability to an optimal level for neuritogenesis. Our findings shed light on the mechanisms underlying the HDAC6-mediated coupling of the two ubiquitous cytoskeletal systems during neural development. C1 [Ageta-Ishihara, Natsumi; Ohshima, Chika; Hamamura, Yuki; Kinoshita, Makoto] Nagoya Univ, Grad Sch Sci, Div Biol Sci, Nagoya, Aichi 4648602, Japan. [Miyata, Takaki] Nagoya Univ, Grad Sch Med, Dept Anat & Cell Biol, Nagoya, Aichi 4668550, Japan. [Watanabe, Masahiko] Hokkaido Univ, Grad Sch Med, Dept Anat, Sapporo, Hokkaido 0608638, Japan. [Sato, Yoshikatsu; Higashiyama, Tetsuya] Nagoya Univ, Inst Transformat Bio Mol, Nagoya, Aichi 4648602, Japan. [Mazitschek, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Mazitschek, Ralph] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Bito, Haruhiko] Univ Tokyo, Grad Sch Med, Dept Neurochem, Tokyo 1130033, Japan. RP Kinoshita, M (reprint author), Nagoya Univ, Grad Sch Sci, Div Biol Sci, Nagoya, Aichi 4648602, Japan. EM kinoshita.makoto@c.mbox.nagoya-u.ac.jp RI Bito, Haruhiko/A-8635-2008; Sato, Yoshikatsu/I-6129-2014; MIYATA, TAKAKI/I-7066-2014 FU Comprehensive Brain Science Network; Ministry of Education, Science, Sports and Culture of Japan; Takeda Science Foundation; Astellas Foundation; Suzuken Memorial Foundation; Narishige Neuroscience Research Foundation; NIH [P50A086355] FX We thank M. Masaoka and Y. Enomoto (Nagoya University), respectively for the technical help in in utero electroporation and FACS analysis, T-P. Yao and Y-S. Gao (Duke University) for HDAC6 antibody, E. T. Spiliotis (Drexel University) for polyglutamylated tubulin antibody, Y. Kiyosue (RIKEN CDB) for GFP-EB1 plasmid, M. Yoshida (RIKEN) for HDAC6-HA plasmid, and R. Y. Tsien (University of California, San Diego) for mCherry cDNA. A part of the microscopic analysis was done at Nagoya University Advanced Live Imaging Center funded by Japan Advanced Plant Science Network. This work was supported in part by Grant-in-Aid for Scientific Research (B) (to M. K.), Grant-in-Aid for Young Investigator (B) (to N.A.-I.), Grants-in-Aid for Scientific Research on Innovative Areas 'Synapse Neurocircuit Pathology' and 'Micro Psychopathology' (to M. K.), 'Cross-talk between moving cells and microenvironment as a basis of emerging order in multicellular system' (to T. M.), Technical Supports for Fluorescent Probes and Imaging and for Antibody Production from Comprehensive Brain Science Network (to N.A.-I., M. W., H. B., M. K.), each from the Ministry of Education, Science, Sports and Culture of Japan, and by the research grants from Takeda Science Foundation, Astellas Foundation, Suzuken Memorial Foundation, Narishige Neuroscience Research Foundation (to N.A.-I.), and NIH grant P50A086355 (to R. M.). NR 55 TC 24 Z9 25 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD OCT PY 2013 VL 4 AR 2532 DI 10.1038/ncomms3532 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 245MO UT WOS:000326468000002 PM 24113571 ER PT J AU Ahveninen, J Huang, S Nummenmaa, A Belliveau, JW Hung, AY Jaaskelainen, IP Rauschecker, JP Rossi, S Tiitinen, H Raij, T AF Ahveninen, Jyrki Huang, Samantha Nummenmaa, Aapo Belliveau, John W. Hung, An-Yi Jaaskelainen, Iiro P. Rauschecker, Josef P. Rossi, Stephanie Tiitinen, Hannu Raij, Tommi TI Evidence for distinct human auditory cortex regions for sound location versus identity processing SO NATURE COMMUNICATIONS LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; HUMAN BRAIN; CEREBRAL CONNECTIONS; HEMISPHERIC LESIONS; FUNCTIONAL IMPACT; PARIETAL CORTEX; TEMPORAL-LOBE; LOCALIZATION; SPEECH AB Neurophysiological animal models suggest that anterior auditory cortex (AC) areas process sound identity information, whereas posterior ACs specialize in sound location processing. In humans, inconsistent neuroimaging results and insufficient causal evidence have challenged the existence of such parallel AC organization. Here we transiently inhibit bilateral anterior or posterior AC areas using MRI-guided paired-pulse transcranial magnetic stimulation (TMS) while subjects listen to Reference/Probe sound pairs and perform either sound location or identity discrimination tasks. The targeting of TMS pulses, delivered 55-145 ms after Probes, is confirmed with individual-level cortical electric-field estimates. Our data show that TMS to posterior AC regions delays reaction times (RT) significantly more during sound location than identity discrimination, whereas TMS to anterior AC regions delays RTs significantly more during sound identity than location discrimination. This double dissociation provides direct causal support for parallel processing of sound identity features in anterior AC and sound location in posterior AC. C1 [Ahveninen, Jyrki; Huang, Samantha; Nummenmaa, Aapo; Belliveau, John W.; Hung, An-Yi; Rossi, Stephanie; Raij, Tommi] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Belliveau, John W.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Jaaskelainen, Iiro P.; Tiitinen, Hannu] Aalto Univ, Sch Sci, Dept Biomed Engn & Computat Sci BECS, FIN-00076 Espoo, Aalto, Finland. [Rauschecker, Josef P.] Georgetown Univ, Med Ctr, Dept Neurosci, Lab Integrat Neurosci & Cognit, Washington, DC 20057 USA. RP Ahveninen, J (reprint author), Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Bldg 149,13th St, Charlestown, MA 02129 USA. EM jyrki@nmr.mgh.harvard.edu RI Jaaskelainen, Iiro/C-7392-2012 OI Jaaskelainen, Iiro/0000-0001-6001-6950 FU National Institutes of Health (NIH) [R21DC010060, R01MH083744, R01HD040712, R01NS037462, R01NS048279, K99EB015445]; NIH/National Institute of Biomedical Imaging and Bioengineering (NIBIB) [P41EB015896]; Center for Functional Neuroimaging Techniques, CFNT; NIH Shared Instrumentation Grant S10-RR024694; Harvard Clinical and Translational Science Center [NCRR-NIH UL1 RR025758, NCRR-NIH UL1 TR000170]; Academy Of Finland [130412]; NIH [R56NS052494]; National Science Foundation [PIRE-OISE-0730255] FX We thank Mary O'Hara, Nancy Shearer, Chinmayi Tengshe and Lawrence White, as well as Drs Wei- Tang Chang, Sharon Furtak, Matti Ha "ma "la "inen and Norbert Kopc. o. This research was supported by the National Institutes of Health (NIH) Grants R21DC010060, R01MH083744, R01HD040712, R01NS037462, R01NS048279 and K99EB015445. The research environment was supported by the NIH/National Institute of Biomedical Imaging and Bioengineering (NIBIB) Grant P41EB015896 (Center for Functional Neuroimaging Techniques, CFNT), NIH Shared Instrumentation Grant S10-RR024694, and the Harvard Clinical and Translational Science Center (Harvard Catalyst; NCRR-NIH UL1 RR025758; NCRR-NIH UL1 TR000170). I. P. J. was supported by the Academy Of Finland Grant 130412, and J. P. R was supported by the NIH Grant R56NS052494 and by the National Science Foundation Grant NSF PIRE-OISE-0730255. The content is solely the responsibility of the authors and does not necessarily represent NR 60 TC 22 Z9 22 U1 2 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD OCT PY 2013 VL 4 AR 2585 DI 10.1038/ncomms3585 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 245NM UT WOS:000326470400029 PM 24121634 ER PT J AU Chauhan, VP Martin, JD Liu, H Lacorre, DA Jain, SR Kozin, SV Stylianopoulos, T Mousa, AS Han, XX Adstamongkonkul, P Popovic, Z Huang, PG Bawendi, MG Boucher, Y Jain, RK AF Chauhan, Vikash P. Martin, John D. Liu, Hao Lacorre, Delphine A. Jain, Saloni R. Kozin, Sergey V. Stylianopoulos, Triantafyllos Mousa, Ahmed S. Han, Xiaoxing Adstamongkonkul, Pichet Popovic, Zoran Huang, Peigen Bawendi, Moungi G. Boucher, Yves Jain, Rakesh K. TI Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels SO NATURE COMMUNICATIONS LA English DT Article ID II TYPE-2 RECEPTOR; GROWTH-FACTOR-BETA; INTERSTITIAL FLUID PRESSURE; PANCREATIC STELLATE CELLS; BREAST-CANCER; SOLID STRESS; TGF-BETA; GENE-EXPRESSION; AORTIC-ANEURYSM; MOUSE MODEL AB Cancer and stromal cells actively exert physical forces (solid stress) to compress tumour blood vessels, thus reducing vascular perfusion. Tumour interstitial matrix also contributes to solid stress, with hyaluronan implicated as the primary matrix molecule responsible for vessel compression because of its swelling behaviour. Here we show, unexpectedly, that hyaluronan compresses vessels only in collagen-rich tumours, suggesting that collagen and hyaluronan together are critical targets for decompressing tumour vessels. We demonstrate that the angiotensin inhibitor losartan reduces stromal collagen and hyaluronan production, associated with decreased expression of profibrotic signals TGF-beta 1, CCN2 and ET-1, downstream of angiotensin-II-receptor-1 inhibition. Consequently, losartan reduces solid stress in tumours resulting in increased vascular perfusion. Through this physical mechanism, losartan improves drug and oxygen delivery to tumours, thereby potentiating chemotherapy and reducing hypoxia in breast and pancreatic cancer models. Thus, angiotensin inhibitors - inexpensive drugs with decades of safe use - could be rapidly repurposed as cancer therapeutics. C1 [Chauhan, Vikash P.; Martin, John D.; Liu, Hao; Lacorre, Delphine A.; Jain, Saloni R.; Kozin, Sergey V.; Stylianopoulos, Triantafyllos; Mousa, Ahmed S.; Han, Xiaoxing; Adstamongkonkul, Pichet; Huang, Peigen; Boucher, Yves; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Chauhan, Vikash P.; Martin, John D.; Liu, Hao; Lacorre, Delphine A.; Jain, Saloni R.; Kozin, Sergey V.; Stylianopoulos, Triantafyllos; Mousa, Ahmed S.; Han, Xiaoxing; Adstamongkonkul, Pichet; Huang, Peigen; Boucher, Yves; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chauhan, Vikash P.; Adstamongkonkul, Pichet] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Martin, John D.; Jain, Saloni R.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Liu, Hao] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA. [Stylianopoulos, Triantafyllos] Univ Cyprus, Dept Mech & Mfg Engn, CY-1678 Nicosia, Cyprus. [Popovic, Zoran; Bawendi, Moungi G.] MIT, Dept Chem, Cambridge, MA 02139 USA. 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 RI Martin, John/L-6892-2016; OI Martin, John/0000-0002-9828-8203; Stylianopoulos, Triantafyllos/0000-0002-3093-1696 FU U.S. National Cancer Institute [P01-CA080124, R01-CA126642, R01-CA085140, R01-CA115767, R01-CA098706]; U.S. Department of Defense Breast Cancer Research Program Innovator Award [W81XWH-10-1-0016]; Dana-Farber Harvard Cancer Center/MIT Koch Institute Bridge Project grant from the Lustgarten Foundation; Ruth L. Kirschstein NRSA Post-doctoral Fellowship from the NIH [T32-CA073479] FX We thank Julia Kahn, Sylvie Roberge, Christina Koppel, Carolyn Smith and Eve Smith for technical assistance. We also thank Drs Dan G. Duda, Jeffrey Clark and Pieter Timmermans for helpful discussions, and Dr Nabeel Bardeesy for providing us with AK4.4 cells. This research was primarily supported by the U.S. National Cancer Institute Grants P01-CA080124, R01-CA126642, R01-CA085140, R01-CA115767 and R01-CA098706, and by the U.S. Department of Defense Breast Cancer Research Program Innovator Award W81XWH-10-1-0016. Additional support was provided by a Dana-Farber Harvard Cancer Center/MIT Koch Institute Bridge Project grant from the Lustgarten Foundation. V.P.C. is supported by a Ruth L. Kirschstein NRSA Post-doctoral Fellowship from the NIH, T32-CA073479. NR 63 TC 123 Z9 124 U1 8 U2 68 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD OCT PY 2013 VL 4 AR 2516 DI 10.1038/ncomms3516 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 245MK UT WOS:000326467600001 PM 24084631 ER PT J AU Sander, JD Ramirez, CL Linder, SJ Pattanayak, V Shoresh, N Ku, MC Foden, JA Reyon, D Bernstein, BE Liu, DR Joung, JK AF Sander, Jeffry D. Ramirez, Cherie L. Linder, Samantha J. Pattanayak, Vikram Shoresh, Noam Ku, Manching Foden, Jennifer A. Reyon, Deepak Bernstein, Bradley E. Liu, David R. Joung, J. Keith TI In silico abstraction of zinc finger nuclease cleavage profiles reveals an expanded landscape of off-target sites SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENOME; CELLS; CAS9 AB Gene-editing nucleases enable targeted modification of DNA sequences in living cells, thereby facilitating efficient knockout and precise editing of endogenous loci. Engineered nucleases also have the potential to introduce mutations at off-target sites of action. Such unintended alterations can confound interpretation of experiments and can have implications for development of therapeutic applications. Recently, two improved methods for identifying the off-target effects of zinc finger nucleases (ZFNs) were described-one using an in vitro cleavage site selection method and the other exploiting the insertion of integration-defective lentiviruses into nuclease-induced double-stranded DNA breaks. However, application of these two methods to a ZFN pair targeted to the human CCR5 gene led to identification of largely non-overlapping off-target sites, raising the possibility that additional off-target sites might exist. Here, we show that in silico abstraction of ZFN cleavage profiles obtained from in vitro cleavage site selections can greatly enhance the ability to identify potential off-target sites in human cells. Our improved method should enable more comprehensive profiling of ZFN specificities. C1 [Sander, Jeffry D.; Ramirez, Cherie L.; Linder, Samantha J.; Ku, Manching; Foden, Jennifer A.; Reyon, Deepak; Bernstein, Bradley E.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA 02129 USA. [Sander, Jeffry D.; Ramirez, Cherie L.; Linder, Samantha J.; Foden, Jennifer A.; Reyon, Deepak; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA. [Sander, Jeffry D.; Ku, Manching; Reyon, Deepak; Bernstein, Bradley E.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ramirez, Cherie L.; Joung, J. Keith] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA. [Pattanayak, Vikram; Liu, David R.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 01238 USA. [Shoresh, Noam; Bernstein, Bradley E.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Bernstein, Bradley E.; Liu, David R.] Howard Hughes Med Inst, Chevy Chase, MD 02815 USA. RP Sander, JD (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA 02129 USA. EM jsander@alumni.iastate.edu FU National Institutes of Health (NIH) [DP1 GM105378, NIH P50 HG005550]; Defense Advanced Research Projects Agency (DARPA) [W911NF-11-2-0056]; Jim and Ann Orr Massachusetts General Hospital (MGH) Research Scholar Award; NIH [DP1 GM105378, T32 CA009216]; National Science Foundation Graduate Research Fellowship; Ford Foundation Predoctoral Fellowship; National Science Foundation (NSF) [DBI-0923827]; DARPA [HR0011-11-2-0003, N66001-12-C-4207]; Howard Hughes Medical Institute; National Institute of General Medical Sciences [T32GM007753]; National Human Genome Research Institute [U54 HG004570] FX National Institutes of Health (NIH) Director's Pioneer Award [DP1 GM105378], [NIH P50 HG005550] and Defense Advanced Research Projects Agency (DARPA) [W911NF-11-2-0056 to J.K.J.]; The Jim and Ann Orr Massachusetts General Hospital (MGH) Research Scholar Award (to J.K.J.); [NIH T32 CA009216 to J.D.S.]; National Science Foundation Graduate Research Fellowship and a Ford Foundation Predoctoral Fellowship (to C. L. R.); National Science Foundation (NSF) ward [DBI-0923827 to D. R.]; [DARPA HR0011-11-2-0003, DARPA N66001-12-C-4207] and the Howard Hughes Medical Institute (to V. P. and D. R. L.); Award number [T32GM007753 to V. P.] from the National Institute of General Medical Sciences. National Human Genome Research Institute Grant [U54 HG004570 to N.S., M. K., B. E. B.]. Funding for open access charge: NIH [DP1 GM105378]. NR 14 TC 26 Z9 27 U1 1 U2 10 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. PD OCT PY 2013 VL 41 IS 19 AR e181 DI 10.1093/nar/gkt716 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 239SC UT WOS:000326044700004 PM 23945932 ER PT J AU Chi, AS AF Chi, Andrew S. TI Is There a Role for Bevacizumab in the Treatment of Glioblastoma? SO ONCOLOGIST LA English DT Editorial Material C1 [Chi, Andrew S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Chi, AS (reprint author), 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM chi.andrew@mgh.harvard.edu NR 10 TC 3 Z9 3 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 PD OCT PY 2013 VL 18 IS 10 BP 1080 EP 1082 DI 10.1634/theoncologist.2013-0296 PG 3 WC Oncology SC Oncology GA 243NK UT WOS:000326322900003 PM 24056893 ER PT J AU Tucker, RP Judah, MR O'Keefe, VM Mills, AC Lechner, WV Davidson, CL Grant, DM Wingate, LR AF Tucker, Raymond P. Judah, Matt R. O'Keefe, Victoria M. Mills, Adam C. Lechner, William V. Davidson, Collin L. Grant, DeMond M. Wingate, LaRicka R. TI Humor styles impact the relationship between symptoms of social anxiety and depression SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE Humor styles; Humor; Social anxiety; Depression; Dysphoria ID SUICIDAL IDEATION; PHOBIA; RISK; DISORDER; ADULTS; COMORBIDITY; LONELINESS; VALIDATION; PREDICTORS; MODEL AB Recent research suggests that examining humor styles may contribute to our understanding of clinical problems, such as risk and resiliency. The goal of the current study was to examine whether humor styles moderate the association between social anxiety and depressive symptoms in an unselected sample. Three-hundred and six participants (66% female) at a large Southern US university completed self-report measures of humor styles and symptoms of social anxiety and depression. Regression analyses suggested that affiliative and self-defeating humor styles individually moderated the relationship between social anxiety and depressive symptoms. Clinical implications regarding the monitoring of humor use as a means of understanding the maintenance of depressive symptoms among socially anxious individuals are discussed. (C) 2013 Published by Elsevier Ltd. C1 [Tucker, Raymond P.; Judah, Matt R.; O'Keefe, Victoria M.; Mills, Adam C.; Lechner, William V.; Grant, DeMond M.; Wingate, LaRicka R.] Oklahoma State Univ, Stillwater, OK 74078 USA. [Davidson, Collin L.] Denver VA Med Ctr, VA VISN MIRECC 19, Denver, CO USA. RP Wingate, LR (reprint author), Oklahoma State Univ, Dept Psychol, 116 North Murray Hall, Stillwater, OK 74078 USA. EM laricka.wingate@okstate.edu OI Grant, DeMond/0000-0002-5231-6563 NR 35 TC 3 Z9 4 U1 1 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD OCT PY 2013 VL 55 IS 7 BP 823 EP 827 DI 10.1016/j.paid.2013.07.008 PG 5 WC Psychology, Social SC Psychology GA 214SL UT WOS:000324156000018 ER PT J AU Logue, MW Solovieff, N Leussis, MP Wolf, EJ Melista, E Baldwin, C Koenen, KC Petryshen, TL Miller, MW AF Logue, Mark W. Solovieff, Nadia Leussis, Melanie P. Wolf, Erika J. Melista, Efthymia Baldwin, Clinton Koenen, Karestan C. Petryshen, Tracey L. Miller, Mark W. TI The ankyrin-3 gene is associated with posttraumatic stress disorder and externalizing comorbidity SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE ANK3; Posttraumatic stress disorder; Externalizing; Genetic association; Candidate gene ID GENOME-WIDE ASSOCIATION; LONGITUDINAL DATA-ANALYSIS; MULTILOCUS GENOTYPE DATA; BIPOLAR-DISORDER; ANK3; SCHIZOPHRENIA; INDIVIDUALS; INFERENCE; VARIANTS; BRAIN AB Background: The ankyrin 3 gene (ANK3) produces the ankyrin G protein that plays an integral role in regulating neuronal activity. Previous studies have linked ANK3 to bipolar disorder and schizophrenia. A recent mouse study suggests that ANK3 may regulate behavioral disinhibition and stress reactivity. This led us to hypothesize that ANK3 might also be associated with stress-related psychopathology such as posttraumatic stress disorder (PTSD), as well as disorders of the externalizing spectrum such as antisocial personality disorder and substance-related disorders that are etiologically linked to impulsivity and temperamental disinhibition. Methods: We examined the possibility of association between ANK3 SNPs and both PTSD and externalizing (defined by a factor score representing a composite of adult antisociality and substance abuse) in a cohort of white non-Hispanic combat veterans and their intimate partners (n = 554). Initially, we focused on rs9804190-a SNP previously reported to be associated With bipolar disorder, schizophrenia, and ankyrin G expression in brain. Then we examined 358 additional ANK3 SNPs utilizing a multiple-testing correction. Results: rs9804190 was associated with both externalizing and PTSD (p = 0.028 and p = 0.042 respectively). Analysis of other ANK3 SNPs identified several that were more strongly associated with either trait. The most significant association with externalizing was observed at rs1049862 (p = 0.00040, p(corrected) = 0.60). The most significant association with PTSD (p = 0.00060, p(corrected) = 0.045) was found with three SNPs in complete linkage disequilibrium (LD)-rs28932171, rs11599164, and rs17208576. Conclusions: These findings support a role of ANK3 in risk of stress-related and externalizing disorders, beyond its previous associations with bipolar disorder and schizophrenia. Published by Elsevier Ltd. C1 [Logue, Mark W.; Melista, Efthymia; Baldwin, Clinton] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Logue, Mark W.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Solovieff, Nadia; Leussis, Melanie P.; Petryshen, Tracey L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Solovieff, Nadia; Leussis, Melanie P.; Petryshen, Tracey L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Solovieff, Nadia; Petryshen, Tracey L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Solovieff, Nadia; Leussis, Melanie P.; Petryshen, Tracey L.] Broad Inst Harvard & Massachusetts Inst Technol, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Wolf, Erika J.; Miller, Mark W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Leussis, Melanie P.] Emmanuel Coll, Dept Psychol, Boston, MA USA. [Wolf, Erika J.; Miller, Mark W.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Koenen, Karestan C.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. RP Miller, MW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B 2, 150 South Huntington Ave, Boston, MA 02130 USA. EM petryshen@chgr.mgh.harvard.edu; mark.miller5@va.gov RI Miller, Mark/G-7322-2011; Koenen, Karestan/K-5402-2014; OI Miller, Mark/0000-0001-6393-8563; Koenen, Karestan/0000-0003-3293-4281; Wolf, Erika/0000-0003-2666-2435 FU Department of Veterans Affairs, the Stanley National Institute of Mental Health FX Funding was provided by the Department of Veterans Affairs, the Stanley National Institute of Mental Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 14 Z9 15 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD OCT PY 2013 VL 38 IS 10 BP 2249 EP 2257 DI 10.1016/j.psyneuen.2013.04.013 PG 9 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 242BZ UT WOS:000326213700031 PM 23796624 ER PT J AU Hess, DR AF Hess, Dean R. TI Science and Evidence: Separating Fact from Fiction SO RESPIRATORY CARE LA English DT Article DE clinical practice guideline; evidence-base medicine; meta-analysis; systematic review ID RESPIRATORY-DISTRESS-SYNDROME; CLINICAL-PRACTICE GUIDELINES; ACUTE LUNG INJURY; RANDOMIZED CONTROLLED-TRIAL; HIGH-FREQUENCY OSCILLATION; EVIDENCE-BASED MEDICINE; CONVENTIONAL MECHANICAL VENTILATION; AIR-FLOW LIMITATION; LOWER TIDAL VOLUMES; NONINVASIVE VENTILATION AB Evidence-based medicine (EBM) is the integration of individual clinical expertise with the best available research evidence from systematic research and the patient's values and expectations. A hierarchy of evidence can be used to assess the strength upon which clinical decisions are made. The efficient approach to finding the best evidence is to identify systematic reviews or evidence-based clinical practice guidelines. Respiratory therapies that evidence supports include noninvasive ventilation for appropriately selected patients, lung-protective ventilation, and ventilator discontinuation protocols. Evidence does not support use of weaning parameters, albuterol for ARDS, and high frequency oscillatory ventilation for adults. Therapy with equivocal evidence includes airway clearance, selection of an aerosol delivery device, and PEEP for ARDS. Although all tenets of EBM are not universally accepted, the principles of EBM nonetheless provide a valuable approach to respiratory care practice. C1 [Hess, Dean R.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Hess, Dean R.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 73 TC 1 Z9 1 U1 0 U2 5 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 EI 1943-3654 J9 RESP CARE JI Respir. Care PD OCT PY 2013 VL 58 IS 10 BP 1649 EP 1661 DI 10.4187/respcare.02591 PG 13 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 245RH UT WOS:000326481000012 PM 24064624 ER PT J AU Fernandez, JF Restrepo, MI AF Fernandez, Juan Felipe Restrepo, Marcos I. TI Too Passive to Prevent Ventilator-Associated Pneumonia SO RESPIRATORY CARE LA English DT Editorial Material ID SUBGLOTTIC SECRETION DRAINAGE; CARE SAFETY NETWORK; ENDOTRACHEAL-TUBES; METAANALYSIS; CUFF C1 [Fernandez, Juan Felipe; Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm Dis & Crit Care, San Antonio, TX 78229 USA. [Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. [Restrepo, Marcos I.] Evidence Based Res Disseminat & Implementat Ctr, San Antonio, TX USA. RP Restrepo, MI (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Pulm Dis & Crit Care, 7400 Merton Minter St,MC 111E, San Antonio, TX 78229 USA. EM Restrepom@uthscsa.edu RI Restrepo, Marcos/H-4442-2014 FU NHLBI NIH HHS [K23 HL096054] NR 13 TC 0 Z9 0 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 EI 1943-3654 J9 RESP CARE JI Respir. Care PD OCT PY 2013 VL 58 IS 10 BP 1704 EP 1706 DI 10.4187/respcare.02803 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 245RH UT WOS:000326481000017 PM 24064628 ER PT J AU Kim, HG Tan, L Weisberg, EL Liu, FY Canning, P Choi, HG Ezell, SA Wu, H Zhao, Z Wang, JH Mandinova, A Griffin, JD Bullock, AN Liu, QS Lee, SW Gray, NS AF Kim, Hyung-Gu Tan, Li Weisberg, Ellen L. Liu, Feiyang Canning, Peter Choi, Hwan Geun Ezell, Scott A. Wu, Hong Zhao, Zheng Wang, Jinhua Mandinova, Anna Griffin, James D. Bullock, Alex N. Liu, Qingsong Lee, Sam W. Gray, Nathanael S. TI Discovery of a Potent and Selective DDR1 Receptor Tyrosine Kinase Inhibitor SO ACS CHEMICAL BIOLOGY LA English DT Article ID DISCOIDIN DOMAIN RECEPTOR-1; SOMATIC MUTATIONS; ABL INHIBITORS; ACTIVATION; EXPRESSION; GENES; OVEREXPRESSION; DASATINIB; CARCINOMA; NILOTINIB AB The DDR1 receptor tyrosine kinase is activated by matrix collagens and has been implicated in numerous cellular functions such as proliferation, differentiation, adhesion, migration, and invasion. Here we report the discovery of a potent and selective DDR1 inhibitor, DDR1-IN-1, and present the 2.2 angstrom DDR1 co-crystal structure. DDR1-IN-1 binds to DDR1 in the 'DFG-out' conformation and inhibits DDR1 autophosphorylation in cells at submicromolar concentrations with good selectivity as assessed against a panel of 451 kinases measured using the KinomeScan technology. We identified a mutation in the hinge region of DDR1, G707A, that confers >20-fold resistance to the ability of DDR1-IN-1 to inhibit DDR1 autophosphorylation and can be used to establish what pharmacology is DDR1-dependent. A combinatorial screen of DDR1-IN-1 with a library of annotated kinase inhibitors revealed that inhibitors of PI3K and mTOR such as GSK2126458 potentiate the antiproliferative activity of DDR1-IN-1 in colorectal cancer cell lines. DDR1-IN-1 provides a useful pharmacological probe for DDR1-dependent signal transduction. C1 [Kim, Hyung-Gu; Ezell, Scott A.; Mandinova, Anna; Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Kim, Hyung-Gu; Ezell, Scott A.; Mandinova, Anna; Lee, Sam W.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Tan, Li; Weisberg, Ellen L.; Liu, Feiyang; Choi, Hwan Geun; Wu, Hong; Wang, Jinhua; Griffin, James D.; Liu, Qingsong; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Tan, Li; Wang, Jinhua; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Liu, Feiyang; Wu, Hong; Zhao, Zheng; Liu, Qingsong] Chinese Acad Sci, High Field Magnet Lab, Hefei 230031, Anhui, Peoples R China. [Canning, Peter; Bullock, Alex N.] Univ Oxford, Struct Genom Consortium, Oxford OX3 7DQ, England. RP Liu, QS (reprint author), Chinese Acad Sci, High Field Magnet Lab, POB 1110, Hefei 230031, Anhui, Peoples R China. EM Qsliu97@hmfl.ac.cn; swlee@partners.org; nathanael_gray@dfci.harvard.edu OI Canning, Peter/0000-0001-9678-4169; liu, qing song/0000-0002-7829-2547 FU National Institutes of Health [U54 HG006097, CA154303]; Chinese Academy of Sciences; NIH; MGH; AbbVie; Boehringer Ingelheim; Canada Foundation for Innovation; Canadian Institutes for Health Research; Genome Canada; GlaxoSmithKline; Janssen; Lilly Canada; Novartis Research Foundation; Ontario Ministry of Economic Development and Innovation; Pfizer; Takeda; Wellcome Trust [092809/Z/10/Z] FX We thank National Institutes of Health (U54 HG006097 and CA154303) for support of L.T., H.G.C., J.W., Q.L., and N.S.G. and the Chinese Academy of Sciences for training grant in support of F.L. and W.H.; H.-G.K, S.A.E., and S.W.L. were supported by NIH grants and MGH Interim funds. The SGC is a registered charity (number 1097737) that receives funds from AbbVie, Boehringer Ingelheim, the Canada Foundation for Innovation, the Canadian Institutes for Health Research, Genome Canada, GlaxoSmithKline, Janssen, Lilly Canada, the Novartis Research Foundation, the Ontario Ministry of Economic Development and Innovation, Pfizer, Takeda, and the Wellcome Trust [092809/Z/10/Z] NR 21 TC 32 Z9 35 U1 2 U2 36 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 EI 1554-8937 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD OCT PY 2013 VL 8 IS 10 BP 2145 EP 2150 DI 10.1021/cb400430t PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 240TU UT WOS:000326121400007 PM 23899692 ER PT J AU Grant, SS Kawate, T Nag, PP Silvis, MR Gordon, K Stanley, SA Kazyanskaya, E Nietupski, R Golas, A Fitzgerald, M Cho, S Franzblau, SG Hung, DT AF Grant, Sarah Schmidt Kawate, Tomohiko Nag, Partha P. Silvis, Melanie R. Gordon, Katherine Stanley, Sarah A. Kazyanskaya, Edward Nietupski, Raymond Golas, Aaron Fitzgerald, Michael Cho, Sanghyun Franzblau, Scott G. Hung, Deborah T. TI Identification of Novel Inhibitors of Nonreplicating Mycobacterium tuberculosis Using a Carbon Starvation Model SO ACS CHEMICAL BIOLOGY LA English DT Article ID IN-VITRO; STRINGENT RESPONSE; TUBERCLE-BACILLI; ATP HOMEOSTASIS; MURINE MODEL; PERSISTENCE; DORMANT; GROWTH; DIARYLQUINOLINES; METABOLISM AB During Mycobacterium tuberculosis infection, a population of bacteria is thought to exist in a nonreplicating state, refractory to antibiotics, which may contribute to the need for prolonged antibiotic therapy. The identification of inhibitors of the nonreplicating state provides tools that can be used to probe this hypothesis and the physiology of this state. The development of such inhibitors also has the potential to shorten the duration of antibiotic therapy required. Here we describe the development of a novel nonreplicating assay amenable to high-throughput chemical screening coupled with secondary assays that use carbon starvation as the in vitro model. Together these assays identify compounds with activity against replicating and nonreplicating M. tuberculosis as well as compounds that inhibit the transition from nonreplicating to replicating stages of growth. Using these assays we successfully screened over 300,000 compounds and identified 786 inhibitors of nonreplicating M. tuberculosis In order to understand the relationship among different nonreplicating models, we tested 52 of these molecules in a hypoxia model, and four different chemical scaffolds in a stochastic persister model, and a streptomycin-dependent model. We found that compounds display varying levels of activity in different models for the nonreplicating state, suggesting important differences in bacterial physiology between models. Therefore, chemical tools identified in this assay may be useful for determining the relevance of different nonreplicating in vitro models to in vivo M. tuberculosis infection. Given our current limited understanding, molecules that are active across multiple models may represent more promising candidates for further development. C1 [Grant, Sarah Schmidt; Kawate, Tomohiko; Nag, Partha P.; Silvis, Melanie R.; Gordon, Katherine; Stanley, Sarah A.; Kazyanskaya, Edward; Nietupski, Raymond; Golas, Aaron; Fitzgerald, Michael; Hung, Deborah T.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Grant, Sarah Schmidt] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Grant, Sarah Schmidt; Kawate, Tomohiko; Stanley, Sarah A.; Hung, Deborah T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Grant, Sarah Schmidt; Kawate, Tomohiko; Stanley, Sarah A.; Hung, Deborah T.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Grant, Sarah Schmidt; Kawate, Tomohiko; Stanley, Sarah A.; Hung, Deborah T.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Cho, Sanghyun; Franzblau, Scott G.] Univ Illinois, Coll Pharm, Inst TB Res, Chicago, IL 60621 USA. RP Hung, DT (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM hung@molbio.mgh.harvard.edu OI Franzblau, Scott/0000-0002-8698-0243; Silvis, Melanie/0000-0002-0732-9744 FU National Institutes of Health [K08AI085033, R03MH087444]; Bill and Melinda Gates Foundation; National Institutes of Health Molecular Libraries Production Centers Network (MLPCN) FX We thank J. Bittker, C. Mulrooney, and the Broad Institute Chemical Biology platform for technical assistance and data management; R. Goldman, B. Laughon, T. Parker, the NIAID and TAACF/SRI for providing the 1113 compound set; Lucille White and SRSBSC for completing the primary starvation screen and secondary logarithmic screen against the 324,545 MLSMR library; J. Gomez for helpful discussion and advice throughout the project; A. Campos-Neto for the M. tuberculosis 18b strain. S.S.G. gratefully acknowledges the National Institutes of Health K08AI085033 for funding. This work was supported through funding from the Bill and Melinda Gates Foundation to D.T.H., National Institutes of Health R03MH087444 to D.T.H., and by the National Institutes of Health Molecular Libraries Production Centers Network (MLPCN; www.mli.nih.gov), which funded primary screening of a 324,545-compound library against M. tuberculosis strain H37Rv at SRI. NR 50 TC 18 Z9 18 U1 2 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 EI 1554-8937 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD OCT PY 2013 VL 8 IS 10 BP 2224 EP 2234 DI 10.1021/cb4004817 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 240TU UT WOS:000326121400017 PM 23898841 ER PT J AU Flynn, JM O'Leary, MN Zambataro, CA Academia, EC Presley, MP Garrett, BJ Zykovich, A Mooney, SD Strong, R Rosen, CJ Kapahi, P Nelson, MD Kennedy, BK Melov, S AF Flynn, James M. O'Leary, Monique N. Zambataro, Christopher A. Academia, Emmeline C. Presley, Michael P. Garrett, Brittany J. Zykovich, Artem Mooney, Sean D. Strong, Randy Rosen, Clifford J. Kapahi, Pankaj Nelson, Michael D. Kennedy, Brian K. Melov, Simon TI Late-life rapamycin treatment reverses age-related heart dysfunction SO AGING CELL LA English DT Article DE RNA-seq; rapamycin; aging; strain echocardiography; RAD; hypertrophy; mTOR ID CARDIAC-HYPERTROPHY; PRESSURE-OVERLOAD; MAMMALIAN TARGET; MTOR INHIBITION; SPAN; BETA; RAD; DIFFERENTIATION; PERFORMANCE; MODULATION AB Summary Rapamycin has been shown to extend lifespan in numerous model organisms including mice, with the most dramatic longevity effects reported in females. However, little is known about the functional ramifications of this longevity-enhancing paradigm in mammalian tissues. We treated 24-month-old female C57BL/6J mice with rapamycin for 3 months and determined health outcomes via a variety of noninvasive measures of cardiovascular, skeletal, and metabolic health for individual mice. We determined that while rapamycin has mild transient metabolic effects, there are significant benefits to late-life cardiovascular function with a reversal or attenuation of age-related changes in the heart. RNA-seq analysis of cardiac tissue after treatment indicated inflammatory, metabolic, and antihypertrophic expression changes in cardiac tissue as potential mechanisms mediating the functional improvement. Rapamycin treatment also resulted in beneficial behavioral, skeletal, and motor changes in these mice compared with those fed a control diet. From these findings, we propose that late-life rapamycin therapy not only extends the lifespan of mammals, but also confers functional benefits to a number of tissues and mechanistically implicates an improvement in contractile function and antihypertrophic signaling in the aged heart with a reduction in age-related inflammation. C1 [Flynn, James M.; O'Leary, Monique N.; Zambataro, Christopher A.; Academia, Emmeline C.; Presley, Michael P.; Garrett, Brittany J.; Zykovich, Artem; Mooney, Sean D.; Kapahi, Pankaj; Kennedy, Brian K.; Melov, Simon] Buck Inst Res Aging, Novato, CA 94945 USA. [Strong, Randy] UTHSC, South Texas Vet Hlth Care Syst, Dept Pharmacol, San Antonio, TX 78229 USA. [Strong, Randy] UTHSC, South Texas Vet Hlth Care Syst, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Rosen, Clifford J.] Maine Med Ctr, Res Inst, Ctr Clin & Translat Res, Scarborough, ME 04074 USA. [Nelson, Michael D.] Cedars Sinai Med Ctr, Inst Heart, Los Angeles, CA 90048 USA. RP Melov, S (reprint author), Buck Inst Res Aging, 8001 Redwood Blvd, Novato, CA 94945 USA. EM smelov@buckinstitute.org FU Larry L. Hillblom Foundation [2007 2/F]; Ellison Medical Foundation; Glenn Foundation for Medical Research; Investigator Initiated Studies Program [39326, 50196]; [PO1 AG025901]; [RO1 AG033373]; [1U01-AG022307]; [T32AG000266] FX Funding support for this research was generously provided by the following grants; PO1 AG025901(SM), RO1 AG033373 (BKK), 1U01-AG022307 (RS), T32AG000266 (Buck Institute), and partial support from the Larry L. Hillblom Foundation Network grant (2007 2/F), the Ellison Medical Foundation (BKK), and the Glenn Foundation for Medical Research (SM and JF). This research was also supported in part by grants from Merck to SM (Investigator Initiated Studies Program, # 39326, and #50196). NR 45 TC 75 Z9 77 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 EI 1474-9726 J9 AGING CELL JI Aging Cell PD OCT PY 2013 VL 12 IS 5 BP 851 EP 862 DI 10.1111/acel.12109 PG 12 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 217RA UT WOS:000324376300013 PM 23734717 ER PT J AU Stein, NR Schorr, Y Krantz, L Dickstein, BD Solomon, Z Horesh, D Litz, BT AF Stein, Nathan R. Schorr, Yonit Krantz, Lillian Dickstein, Benjamin D. Solomon, Zahava Horesh, Danny Litz, Brett T. TI The Differential Impact of Terrorism on Two Israeli Communities SO AMERICAN JOURNAL OF ORTHOPSYCHIATRY LA English DT Article DE Israeli communities; terrorism; exposure to terror; stress-related symptoms; posttraumatic stress disorder; depression; dose-response relationship; rocket attacks; kibbutz; moshav ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH SYMPTOMS; PSYCHOMETRIC PROPERTIES; REPRESENTATIVE SAMPLE; EXPOSURE; TRAUMA; CHECKLIST; ARABS; PTSD; RISK AB The authors evaluated 2 cohorts of individuals from different Israeli communities (Sderot and Otef Aza) that are repeatedly subjected to potentially lethal missile attacks. Although both communities border the Gaza Strip and face similar levels of threat, the authors hypothesized that the Sderot cohort would endorse higher rates of stress-related symptoms because it has fewer mitigating economic and psychosocial resources. The authors further hypothesized that there would be a significant relationship between exposure to terror and psychopathology regardless of community context. To test these predictions, the authors compared the levels of exposure to terror, posttraumatic stress disorder (PTSD), and depression in representative samples of adults from the 2 communities (n=298 and n=152, respectively). Residents of Sderot had a much higher rate of probable PTSD (35.2% vs. 6.6%), and community context was the most important predictor of PTSD and depression. The study also revealed a significant relationship between exposure and psychopathology, but for Sderot residents only. The conclusion is that researchers, mental health workers, and policy makers should pay attention to the influence of community characteristics, such as the availability of resources, the general sense of support, and the level of solidarity, on the mental health response to exposure to terror. C1 [Solomon, Zahava; Horesh, Danny] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. RP Stein, NR (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave 116B-4, Boston, MA 02130 USA. EM nathan.stein@va.gov OI Horesh, Danny/0000-0003-3574-4301 FU National Institute of Mental Health [R21 MH074501] FX This research was supported by Grant R21 MH074501 from the National Institute of Mental Health awarded to Brett Litz. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institute of Mental Health. NR 29 TC 2 Z9 2 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-9432 EI 1939-0025 J9 AM J ORTHOPSYCHIAT JI Am. J. Orthopsychiatr. PD OCT PY 2013 VL 83 IS 4 BP 528 EP 535 DI 10.1111/ajop.12044 PG 8 WC Psychiatry; Social Work SC Psychiatry; Social Work GA 241OP UT WOS:000326176900009 PM 24164524 ER PT J AU Adrianto, I Dozmorov, MG Wiley, GB Ice, JA Li, H Kelly, JA Rasmussen, A Stone, DU Anaya, JM Segal, BM Rhodus, NL Radfar, L Harley, JB James, JA Montgomery, CG Scofield, RH Gaffney, PM Wren, JD Sivils, KL Lessard, CJ AF Adrianto, Indra Dozmorov, Mikhail G. Wiley, Graham B. Ice, John A. Li, He Kelly, Jennifer A. Rasmussen, Astrid Stone, Donald U. Anaya, Juan-Manuel Segal, Barbara M. Rhodus, Nelson L. Radfar, Lida Harley, John B. James, Judith A. Montgomery, Courtney G. Scofield, R. Hal Gaffney, Patrick M. Wren, Jonathan D. Sivils, Kathy L. Lessard, Christopher J. TI RNA-Sequencing Identifies Novel Differentially Expressed Coding and Non-Coding Transcripts In Sjogren's Syndrome SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Adrianto, Indra; Dozmorov, Mikhail G.; Wiley, Graham B.; Ice, John A.; Kelly, Jennifer A.; Rasmussen, Astrid; Montgomery, Courtney G.; Gaffney, Patrick M.; Wren, Jonathan D.; Sivils, Kathy L.; Lessard, Christopher J.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Li, He; Stone, Donald U.; Radfar, Lida; James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Anaya, Juan-Manuel] Univ Rosario, Sch Med & Hlth Sci, Bogota, Colombia. [Segal, Barbara M.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Rhodus, Nelson L.] Univ Minnesota, Minneapolis, MN USA. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [James, Judith A.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Scofield, R. Hal] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RI Anaya, Juan-Manuel/J-1960-2016 OI Anaya, Juan-Manuel/0000-0002-6444-1249 NR 0 TC 1 Z9 1 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 1489 BP S632 EP S633 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359203467 ER PT J AU Anyanwu, CO Fiorentino, D Chung, L Wang, YL Propert, KJ Werth, VP AF Anyanwu, Cynthia O. Fiorentino, David Chung, Lorinda Wang, Yanli Propert, Kathleen J. Werth, Victoria P. TI Validation Of The Cutaneous Dermatomyositis Disease Area and Severity Index: Characterizing Severity and Assessing Responsiveness To Clinical Change SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Anyanwu, Cynthia O.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Fiorentino, David] Stanford Univ, Sch Med, Redwood City, CA USA. [Chung, Lorinda] Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. [Wang, Yanli; Propert, Kathleen J.] Univ Penn, Philadelphia, PA 19104 USA. [Werth, Victoria P.] Univ Penn, Sch Med, Philadelphia, PA 19104 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 1935 BP S824 EP S824 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359204393 ER PT J AU Aquino-Beaton, C Persselin, JE Weinreb, A Fang, MA Singh, JA Duffy, E Elashoff, D Khanna, P Khanna, D AF Aquino-Beaton, Cleopatra Persselin, Jay E. Weinreb, Ari Fang, Meika A. Singh, Jasvinder A. Duffy, Erin Elashoff, David Khanna, Puja Khanna, Dinesh TI Impact Of Educational Attainment On Health-Related Quality Of Life and Healthcare Utilization Among Veterans With Gout SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Aquino-Beaton, Cleopatra; Persselin, Jay E.; Weinreb, Ari; Fang, Meika A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Singh, Jasvinder A.] Univ Alabama, Tuscaloosa, AL USA. [Duffy, Erin] Univ Calif Los Angeles, Los Angeles, CA USA. [Elashoff, David] Univ Calif Los Angeles, Dept Med Stat Core, Los Angeles, CA USA. [Khanna, Puja] Ann Arbor VA, Ann Arbor, MI USA. [Khanna, Dinesh] Univ Michigan, Med Ctr, Ann Arbor, MI 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 1984 BP S846 EP S846 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359204442 ER PT J AU Arvikar, SL Strle, K Collier, DS Fisher, MC Kawai, T Scher, JU Steere, AC AF Arvikar, Sheila L. Strle, Klemen Collier, Deborah S. Fisher, Mark C. Kawai, Toshihisa Scher, Jose U. Steere, Allen C. TI Association Of High Serum Interleukin-23 Levels With Porphyromonas Gingivalis Antibodies In Patients With Early Rheumatoid Arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Arvikar, Sheila L.; Strle, Klemen; Collier, Deborah S.; Fisher, Mark C.; Steere, Allen C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kawai, Toshihisa] Forsyth Inst, Cambridge, MA USA. [Scher, Jose U.] NYU, Hosp Joint Dis, New York, NY 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2409 BP S1029 EP S1029 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359205354 ER PT J AU Barker, AM Battistone, MJ Beck, JP Butler, J Grotzke, M Huhtala, TA Cannella, AC Daikh, DI Fang, MA Lazzari, AA Roldan, P Von Feldt, JM Cannon, GW AF Barker, Andrea M. Battistone, Michael J. Beck, J. Peter Butler, Jorie Grotzke, Marissa Huhtala, Timothy A. Cannella, Amy C. Daikh, David I. Fang, Meika A. Lazzari, Antonio A. Roldan, Pedro Von Feldt, Joan Marie Cannon, Grant W. TI Objective Assessment Of Musculoskeletal Physical Examination Skills During Continuing Education Programs For Primary Care Providers Adds Significant Information Not Obtained Through Self-Assessment SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Barker, Andrea M.; Battistone, Michael J.; Beck, J. Peter; Butler, Jorie; Grotzke, Marissa; Huhtala, Timothy A.; Cannon, Grant W.] Salt Lake City VA, Salt Lake City, UT USA. [Barker, Andrea M.; Battistone, Michael J.; Beck, J. Peter; Grotzke, Marissa; Huhtala, Timothy A.; Cannon, Grant W.] Univ Utah, Salt Lake City, UT USA. [Cannella, Amy C.] Omaha Vet Affairs Hosp, Omaha, NE USA. [Cannella, Amy C.] Univ Nebraska Med Ctr, Omaha, NE USA. [Daikh, David I.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Fang, Meika A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Lazzari, Antonio A.] Boston VA Med Ctr, Boston, MA USA. [Roldan, Pedro] Leesburg VA CBOC, Leesburg, FL USA. [Von Feldt, Joan Marie] Univ Penn Philadelphia VAMC, Philadelphia, PA USA. RI Beck, James Peter/F-9407-2015 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2817 BP S1206 EP S1207 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359206246 ER PT J AU Battistone, MJ Barker, AM Beck, JP Grotzke, M Huhtala, TA Butler, J Cannella, AC Daikh, DI Fang, MA Lazzari, AA Roldan, P Von Feldt, JM Cannon, GW AF Battistone, Michael J. Barker, Andrea M. Beck, J. Peter Grotzke, Marissa Huhtala, Timothy A. Butler, Jorie Cannella, Amy C. Daikh, David I. Fang, Meika A. Lazzari, Antonio A. Roldan, Pedro Von Feldt, Joan Marie Cannon, Grant W. TI Retrospective Self-Assessment Of Pre-Course Competency: A Useful Tool For Musculoskeletal Curriculum Assessment In a Multi-Center, Interprofessional Cohort. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Battistone, Michael J.; Barker, Andrea M.; Beck, J. Peter; Grotzke, Marissa; Huhtala, Timothy A.; Butler, Jorie; Cannon, Grant W.] Salt Lake City VA, Salt Lake City, UT USA. [Battistone, Michael J.; Barker, Andrea M.; Beck, J. Peter; Grotzke, Marissa; Huhtala, Timothy A.; Cannon, Grant W.] Univ Utah, Salt Lake City, UT USA. [Cannella, Amy C.] Omaha Vet Affairs Hosp, Omaha, NE USA. [Cannella, Amy C.] Univ Nebraska, Med Ctr, Omaha, NE USA. [Daikh, David I.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Fang, Meika A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Lazzari, Antonio A.] Boston VA Med Ctr, Boston, MA USA. [Roldan, Pedro] Leesburg VA CBOC, Leesburg, FL USA. [Von Feldt, Joan Marie] Univ Penn, Philadelphia, PA 19104 USA. [Von Feldt, Joan Marie] Philadelphia VAMC, Philadelphia, PA USA. RI Beck, James Peter/F-9407-2015 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 972 BP S415 EP S415 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359202476 ER PT J AU Bharat, A Singh, JA Khanna, P Aquino-Beaton, C Persselin, JE Duffy, E Elashoff, D Khanna, D AF Bharat, Aseem Singh, Jasvinder A. Khanna, Puja Aquino-Beaton, Cleopatra Persselin, Jay E. Duffy, Erin Elashoff, David Khanna, Dinesh TI Racial/Ethnicity Differences In Health-Related Quality Of Life (HRQOL), Functional Ability and Health Care Utilization In Gout Patients SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Bharat, Aseem] Univ Alabama Birmingham, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama, Tuscaloosa, AL USA. [Khanna, Puja] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [Aquino-Beaton, Cleopatra; Persselin, Jay E.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Duffy, Erin] Univ Calif Los Angeles, Los Angeles, CA USA. [Elashoff, David] Univ Calif Los Angeles, Dept Med, Stat Core, Los Angeles, CA 90024 USA. [Khanna, Dinesh] 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 1996 BP S851 EP S852 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359204454 ER PT J AU Brown, LE Frits, MA Iannaccone, CK Weinblatt, ME Shadick, NA Liao, KP AF Brown, Lindsay E. Frits, Michelle A. Iannaccone, Christine K. Weinblatt, Michael E. Shadick, Nancy A. Liao, Katherine P. TI Clinical Characteristics of Rheumatoid Arthritis Patients with Secondary Sjogren's Syndrome and Association with Joint Damage SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Brown, Lindsay E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Frits, Michelle A.; Iannaccone, Christine K.; Weinblatt, Michael E.; Shadick, Nancy A.; Liao, Katherine P.] 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2883 BP S1236 EP S1237 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359206310 ER PT J AU Cannon, GW DuVall, SL Hayden, CL Caplan, L Curtis, JR Michaud, K Mikuls, TR Reimold, AM Collier, DH Joseph, G Harrison, DJ Sauer, BC AF Cannon, Grant W. DuVall, Scott L. Hayden, Candace L. Caplan, Liron Curtis, Jeffrey R. Michaud, Kaleb Mikuls, Ted R. Reimold, Andreas M. Collier, David H. Joseph, George Harrison, David J. Sauer, Brian C. TI US Veterans With Rheumatoid Arthritis Who Switch Among Tumor Necrosis Factor Blocking Agents Have No Additional Clinical Benefit With The Change In Therapy and Incur Higher Costs SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Cannon, Grant W.] Salt Lake City VA, Salt Lake City, UT USA. [Cannon, Grant W.] Univ Utah, Salt Lake City, UT USA. [DuVall, Scott L.; Hayden, Candace L.] VA Salt Lake City Hlth Care Syst, Salt Lake City, UT USA. [DuVall, Scott L.; Hayden, Candace L.] Univ Utah, Sch Med, Salt Lake City, UT USA. [Caplan, Liron] Denver Vet Affairs Med Ctr, Denver, CO USA. [Curtis, Jeffrey R.] Univ Alabama Birmingham, Birmingham, AL USA. [Michaud, Kaleb] Natl Data Bank Rheumat Dis, Omaha, NE USA. [Michaud, Kaleb; Mikuls, Ted R.] Univ Nebraska Med Ctr, Omaha, NE USA. [Mikuls, Ted R.] Omaha VA, Omaha, NE USA. [Reimold, Andreas M.] Dallas VA, Dallas, TX USA. [Reimold, Andreas M.] Univ Texas Southwestern, Dallas, TX USA. [Collier, David H.; Joseph, George; Harrison, David J.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Sauer, Brian C.] George E Wahlen Vet Affairs Med Ctr, Salt Lake City, UT 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 427 BP S184 EP S185 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359201426 ER PT J AU Carruthers, M Topazian, M Khosroshahi, A Witzig, T Oakley, J Hart, P Kelly, L Bergstrom, L Chari, S Stone, J AF Carruthers, Mollie Topazian, Mark Khosroshahi, Arezou Witzig, Thomas Oakley, Judith Hart, Philip Kelly, Lauren Bergstrom, Lori Chari, Suresh Stone, John TI Rituximab For The Treatment Of IgG4-Related Disease: A Prospective Clinical Trial SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Carruthers, Mollie; Oakley, Judith; Kelly, Lauren] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Topazian, Mark] Mayo Clin, Rochester, MA USA. [Khosroshahi, Arezou] Emory Univ, Sch Med, Atlanta, GA USA. [Witzig, Thomas; Hart, Philip; Bergstrom, Lori; Chari, Suresh] Mayo Clin, Rochester, MN USA. [Stone, John] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2649 BP S1128 EP S1129 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359206078 ER PT J AU Carruthers, M Mattoo, H Wallace, ZS Mahajan, V Pillai, S Stone, JH AF Carruthers, Mollie Mattoo, Hamid Wallace, Zachary S. Mahajan, Vinay Pillai, Shiv Stone, John H. TI IgG4+Plasmablasts Are A Novel Biomarker In IgG4-Related Disease. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Carruthers, Mollie; Wallace, Zachary S.; Pillai, Shiv; Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mattoo, Hamid; Mahajan, Vinay] Harvard Univ, Massachusetts Gen Hosp, 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 784 BP S332 EP S332 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359202289 ER PT J AU Criscione-Schreiber, LG Bolster, MB Jonas, BL Sloane, R Hawley, J O'Rourke, KS AF Criscione-Schreiber, Lisa G. Bolster, Marcy B. Jonas, Beth L. Sloane, Richard Hawley, Jeffrey O'Rourke, Kenneth S. TI Expert Panel Consensus On Content Of a Rheumatology Objective Structured Clinical Examination SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Criscione-Schreiber, Lisa G.; Sloane, Richard] Duke Univ Hlth Syst, Durham, NC USA. [Bolster, Marcy B.] Massachussetts Gen Hosp, Boston, MA USA. [Jonas, Beth L.] Univ N Carolina, Chapel Hill, NC USA. [Hawley, Jeffrey] Duke Univ, Sch Nursing, Durham, NC USA. [O'Rourke, Kenneth S.] Wake Forest Sch Med, Winston Salem, NC 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2813 BP S1204 EP S1205 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359206242 ER PT J AU Daikh, DI Battistone, MJ Barker, AM Avins, AL Grotzke, M Fang, MA Lazzari, AA Cannella, AC Roldan, P Von Feldt, JM Cannon, GW AF Daikh, David I. Battistone, Michael J. Barker, Andrea M. Avins, Andy L. Grotzke, Marissa Fang, Meika A. Lazzari, Antonio A. Cannella, Amy C. Roldan, Pedro Von Feldt, Joan Marie Cannon, Grant W. TI Inter-Professional Training Programs For Primary Care Providers Can Successfully Educate Practitioners With Dramatically Different Educational and Training Background Through a Common Mini-Residency Training Program. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Daikh, David I.] San Francisco VA Med Ctr, San Francisco, CA USA. [Daikh, David I.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Battistone, Michael J.; Barker, Andrea M.; Grotzke, Marissa; Cannon, Grant W.] Salt Lake City VA, Salt Lake City, UT USA. [Battistone, Michael J.; Barker, Andrea M.; Grotzke, Marissa; Cannon, Grant W.] Univ Utah, Salt Lake City, UT USA. [Avins, Andy L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Fang, Meika A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Lazzari, Antonio A.] Boston VA Med Ctr, Boston, MA USA. [Cannella, Amy C.] Omaha Vet Affairs Hosp, Omaha, NE USA. [Cannella, Amy C.] Univ Nebraska, Med Ctr, Omaha, NE USA. [Roldan, Pedro] Leesburg VA CBOC, Leesburg, FL USA. [Von Feldt, Joan Marie] Univ Penn, Philadelphia, PA 19104 USA. [Von Feldt, Joan Marie] Philadelphia VAMC, Philadelphia, PA 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 978 BP S417 EP S418 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359202482 ER PT J AU Davis, LA Luong, P Bobba, S Dischinger, H Quinzanos, I Caplan, L AF Davis, Lisa A. Phat Luong Bobba, Sushmitha Dischinger, Hannah Quinzanos, Itziar Caplan, Liron TI Acceptability Of Various Technology-Based Communication Modalities In a Rheumatology Clinic SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Davis, Lisa A.] Denver Hlth & Hosp Author, Denver, CO USA. [Phat Luong; Bobba, Sushmitha; Dischinger, Hannah; Caplan, Liron] Denver Vet Affairs Med Ctr, Denver, CO USA. [Quinzanos, Itziar] Univ Colorado, Sch Med, 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 1907 BP S812 EP S813 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359204366 ER PT J AU Della Torre, E Krause, D Deshpande, V Mahajan, V Mattoo, H Pillai, S Stone, J AF Della Torre, Emanuel Krause, Donald Deshpande, Vikram Mahajan, Vinay Mattoo, Hamid Pillai, Shiv Stone, John TI IgG4-Related Midline Destructive Lesion: Expanding The Spectrum Of Organ Involvement In IgG4-Related Disease SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Della Torre, Emanuel; Deshpande, Vikram; Pillai, Shiv] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Krause, Donald] St Josephs Hosp, Bangor, ME USA. [Mahajan, Vinay; Mattoo, Hamid; Stone, John] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2023 BP S863 EP S863 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359204481 ER PT J AU Ding, YN Hsu, HC Li, J Yang, PA Wu, Q Zajac, AJ Mountz, JD AF Ding, Yanna Hsu, Hui-Chen Li, Jun Yang, PingAr Wu, Qi Zajac, Allan J. Mountz, John D. TI IL-21 Inhibited Follicular Regulatory T Cells To Promote Autoreactive Germinal Center Development In Autoimmune BXD2 Mice SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Ding, Yanna; Li, Jun; Yang, PingAr; Wu, Qi; Zajac, Allan J.; Mountz, John D.] Univ Alabama Birmingham, Birmingham, AL USA. [Hsu, Hui-Chen] Birmingham VA Med Ctr, Birmingham, AL 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2713 BP S1159 EP S1159 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359206143 ER PT J AU Grammatikos, AP Ghosh, D Kyttaris, VC AF Grammatikos, Alexandros P. Ghosh, Debjani Kyttaris, Vasileios C. TI Spleen Tyrosine Kinase (Syk) Regulates Systemic Lupus Erythematosus T Cell Signaling SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Grammatikos, Alexandros P.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Ghosh, Debjani] E Carolina Univ, Brody Sch Med, Greenville, NC USA. [Kyttaris, Vasileios C.] Harvard Univ, Sch Med, BIDMC, Boston, MA 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2701 BP S1154 EP S1154 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359206131 ER PT J AU Hedrich, CM Crispin, JC Rauen, T Ioannidis, C Koga, T Rodriguez, NR Apostolidis, SA Kyttaris, VC Tsokos, GC AF Hedrich, Christian M. Crispin, Jose C. Rauen, Thomas Ioannidis, Christina Koga, Tomohiro Rodriguez, Noe Rodriguez Apostolidis, Sokratis A. Kyttaris, Vasileios C. Tsokos, George C. TI cAMP Responsive Element Modulator (CREM) alpha Governs CD8 Expression and Contributes to the Generation of CD3(+) CD4(-)CD8(-) T Cells in Lupus SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Hedrich, Christian M.; Crispin, Jose C.; Rauen, Thomas; Ioannidis, Christina; Rodriguez, Noe Rodriguez; Kyttaris, Vasileios C.; Tsokos, George C.] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [Koga, Tomohiro; Apostolidis, Sokratis A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2724 BP S1163 EP S1163 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359206153 ER PT J AU Henderson, LA Frugoni, F Hopkins, G de Boer, H Pai, SY Lee, YN Walter, JE Hazen, MM Notarangelo, LD AF Henderson, Lauren A. Frugoni, Francesco Hopkins, Gregory de Boer, Helen Pai, Sung-Yun Lee, Yu Nee Walter, Jolan E. Hazen, Melissa M. Notarangelo, Luigi D. TI Expanding The Spectrum Of Recombination Activating Gene-1 Deficiency To Include Early Onset Autoimmunity SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Henderson, Lauren A.; Frugoni, Francesco; Hopkins, Gregory; de Boer, Helen; Lee, Yu Nee; Hazen, Melissa M.; Notarangelo, Luigi D.] Boston Childrens Hosp, Boston, MA USA. [Pai, Sung-Yun] Dana Farber Canc Inst, Boston, MA 02115 USA. [Walter, Jolan E.] Massachusetts Gen Hosp Children, Boston, MA USA. RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2195 BP S935 EP S936 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359205143 ER PT J AU Hill, E Higgs, JB Sky, K Sit, M Collamer, AN AF Hill, Erica Higgs, Jay B. Sky, Karen Sit, Michelle Collamer, Angelique N. TI Does Starting Allopurinol Prolong Acute Treated Gout? SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Hill, Erica; Higgs, Jay B.] San Antonio Mil Med Ctr, Ft Sam Houston, TX USA. [Sky, Karen] Alaska VA Healthcare Syst, US Dept Vet Affairs, Anchorage, AK USA. [Sit, Michelle] David Grant Med Ctr, Travis AFB, CA USA. [Collamer, Angelique N.] Langley AFB Hosp, Langley AFB, VA 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 1722 BP S730 EP S730 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359204182 ER PT J AU Hirsh, JM Davis, LA Quinzanos, I Keniston, A Caplan, L AF Hirsh, Joel M. Davis, Lisa A. Quinzanos, Itziar Keniston, Angela Caplan, Liron TI Health Literacy Predicts Discrepancies Between Traditional Written Rheumatoid Arthritis Patient Assessments and Verbally-Administered Assessments SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Hirsh, Joel M.; Keniston, Angela] Denver Hlth, Denver, CO USA. [Hirsh, Joel M.; Keniston, Angela] Hosp Author, Denver, CO USA. [Davis, Lisa A.; Quinzanos, Itziar] Univ Colorado, Sch Med, Aurora, CO USA. [Caplan, Liron] Denver Vet Affairs Med Ctr, 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 1031 BP S439 EP S440 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359203017 ER PT J AU Ichinose, K Ushigusa, T Koga, T Tsokos, GC Kawakami, A AF Ichinose, Kunihiro Ushigusa, Takeshi Koga, Tomohiro Tsokos, George C. Kawakami, Atsushi TI Role of Calcium/Calmodulin Kinase IV On Podocyte Function in Lupus Nephritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Ichinose, Kunihiro] Nagasaki Univ, Grad Sch Biomed Sci, Dept Immunol & Rheumatol, Unit Translat Med, Nagasaki 852, Japan. [Ushigusa, Takeshi; Kawakami, Atsushi] Nagasaki Univ, Grad Sch Biomed Sci, Nagasaki 852, Japan. [Koga, Tomohiro] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Tsokos, George C.] Harvard Univ, Sch Med, BIDMC, 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 888 BP S381 EP S381 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359202393 ER PT J AU Kay, J Bossaller, L Schmidt-Lauber, C Abujudeh, HH Vladimer, G Latz, E Fitzgerald, KA Marshak-Rothstein, A Gravallese, EM AF Kay, Jonathan Bossaller, Lukas Schmidt-Lauber, Christian Abujudeh, Hani H. Vladimer, Gregory Latz, Eicke Fitzgerald, Katherine A. Marshak-Rothstein, Ann Gravallese, Ellen M. TI Gadolinium-Based Compounds Induce NLRP3-Dependent IL-1 beta Production and Peritoneal Inflammation. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Kay, Jonathan] UMass Mem Med Ctr, Worcester, MA USA. [Kay, Jonathan; Bossaller, Lukas; Schmidt-Lauber, Christian; Vladimer, Gregory; Latz, Eicke; Fitzgerald, Katherine A.; Marshak-Rothstein, Ann; Gravallese, Ellen M.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Abujudeh, Hani H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Abujudeh, Hani H.] Harvard Univ, Sch Med, Boston, MA USA. RI Latz, Eicke/H-3951-2014 OI Latz, Eicke/0000-0003-1488-5666 NR 0 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2904 BP S1246 EP S1246 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359206331 ER PT J AU Khanna, D Gladue, H Fitzgerald, JD Channick, RN Chung, L Distler, O Furst, D Hachulla, E Humbert, M Langleben, D Mathai, SC Saggar, R Visovatti, SH McLaughlin, V AF Khanna, Dinesh Gladue, Heather Fitzgerald, John D. Channick, Richard N. Chung, Lorinda Distler, Oliver Furst, Daniel Hachulla, Eric Humbert, Marc Langleben, David Mathai, Stephen C. Saggar, Rajeev Visovatti, Scott H. McLaughlin, Vallerie TI Recommendations For Screening and Detection Of Connective-Tissue Disease Associated Pulmonary Arterial Hypertension SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Khanna, Dinesh] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [Gladue, Heather; Visovatti, Scott H.; McLaughlin, Vallerie] Univ Michigan, Ann Arbor, MI 48109 USA. [Fitzgerald, John D.] Univ Calif Los Angeles, Sch Med Rehab 32 59, Los Angeles, CA USA. [Channick, Richard N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chung, Lorinda] Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. [Distler, Oliver] Univ Zurich Hosp, Dept Rheumatol, CH-8091 Zurich, Switzerland. [Furst, Daniel] Univ Calif Los Angeles, Los Angeles, CA USA. [Hachulla, Eric] Claude Huriez Univ Hosp, Lille, France. [Humbert, Marc] Ctr Chirurg Marie Lannelongue, Le Plessis Robinson, France. [Langleben, David] McGill Univ, Montreal, PQ, Canada. [Mathai, Stephen C.] Johns Hopkins Univ, Baltimore, MD USA. [Saggar, Rajeev] St Josephs Hosp, Phoenix, AZ 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2579 BP S1100 EP S1101 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359206012 ER PT J AU Khanna, P Aquino-Beaton, C Singh, JA Duffy, E Elashoff, D Khanna, D AF Khanna, Puja Aquino-Beaton, Cleopatra Singh, Jasvinder A. Duffy, Erin Elashoff, David Khanna, Dinesh TI Predictors Of Outcomes In Tophaceous Gout-Results From a Prospective Cohort At The Veterans Affairs SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Khanna, Puja] Ann Arbor VA, Ann Arbor, MI USA. [Aquino-Beaton, Cleopatra] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Singh, Jasvinder A.] Univ Alabama, Tuscaloosa, AL USA. [Duffy, Erin] Univ Calif Los Angeles, Los Angeles, CA USA. [Elashoff, David] Univ Calif Los Angeles, Dept Med, Stat Core, Los Angeles, CA 90024 USA. [Khanna, Dinesh] Univ Michigan, Med Ctr, Div Rheumatol, Ann Arbor, MI 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2005 BP S856 EP S856 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359204463 ER PT J AU Khanna, P Aquino-Beaton, C Singh, JA Duffy, E Elashoff, D Khanna, D AF Khanna, Puja Aquino-Beaton, Cleopatra Singh, Jasvinder A. Duffy, Erin Elashoff, David Khanna, Dinesh TI Performance Of Gout Impact Scale Of The Gout Assessment Questionnaire In a Longitudinal Observational Study Of Patients With Gout SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Khanna, Puja] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [Aquino-Beaton, Cleopatra] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Singh, Jasvinder A.] Univ Alabama, Tuscaloosa, AL USA. [Duffy, Erin] Univ Calif Los Angeles, Los Angeles, CA USA. [Elashoff, David] Univ Calif Los Angeles, Dept Med, Stat Core, Los Angeles, CA 90024 USA. [Khanna, Dinesh] Univ Michigan, Div Rheumatol, 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 1994 BP S850 EP S851 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359204452 ER PT J AU Kim, SC Schneeweiss, S Glynn, RJ Doherty, M Goldfine, A Solomon, DH AF Kim, Seoyoung C. Schneeweiss, Sebastian Glynn, Robert J. Doherty, Michael Goldfine, Allison Solomon, Daniel H. TI Dipeptidyl Peptidase-4 Inhibitors In Type 2 Diabetes May Reduce The Risk Of Autoimmune Diseases SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Kim, Seoyoung C.; Schneeweiss, Sebastian; Glynn, Robert J.; Doherty, Michael] Brigham & Womens Hosp, Boston, MA 02115 USA. [Goldfine, Allison] Joslin Diabet Ctr, Boston, MA 02215 USA. [Solomon, Daniel H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol,Div Pharmacoepidemiol, Boston, MA 02115 USA. RI Schneeweiss, Sebastian/C-2125-2013 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2658 BP S1133 EP S1133 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359206088 ER PT J AU Kohler, MJ Rempell, J Seton, M AF Kohler, Minna J. Rempell, Joshua Seton, Margaret TI Medical Student Perceptions Of Point-Of-Care Ultrasound In Musculoskeletal Education. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Kohler, Minna J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Rempell, Joshua; Seton, Margaret] 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 974 BP S416 EP S416 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359202478 ER PT J AU Kohler, MJ Rastalsky, N Fraenkel, L AF Kohler, Minna J. Rastalsky, Naina Fraenkel, Liana TI Variable Imaging Characteristics Identified By Point-Of-Care Ultrasound For Greater Trochanteric Pain Syndrome SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Kohler, Minna J.; Rastalsky, Naina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Fraenkel, Liana] Yale Univ, Sch Med, Vet Affairs Connecticut Healthcare Syst, New Haven, CT 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 231 BP S94 EP S95 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359201230 ER PT J AU Koristka, S Cartellieri, M Arndt, C Feldmann, A Michalk, I Bippes, CC Berndt, N Hermsdorf, A Stamova, S Kurien, BT Scofield, RH Farris, AD James, JA Bartsch, H Bachmann, M AF Koristka, Stefanie Cartellieri, Marc Arndt, Claudia Feldmann, Anja Michalk, Irene Bippes, Claudia C. Berndt, Nicole Hermsdorf, Anne Stamova, Slava Kurien, Biji T. Scofield, Robert Hal Farris, A. Darise James, Judith A. Bartsch, Holger Bachmann, Michael TI Bispecific Antibodies For Redirection Of Human Regulatory T Cells To Surface-Inducible Autoantigen La/SS-B SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Koristka, Stefanie; Cartellieri, Marc; Arndt, Claudia; Feldmann, Anja; Michalk, Irene; Bippes, Claudia C.; Berndt, Nicole; Hermsdorf, Anne; Stamova, Slava; Bartsch, Holger; Bachmann, Michael] Carl Gustav Carus TU Dresden, Dresden, Germany. [Kurien, Biji T.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Scofield, Robert Hal] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Oklahoma City, OK 73104 USA. [Scofield, Robert Hal] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Scofield, Robert Hal] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Farris, A. Darise] Oklahoma Med Res Foun, Oklahoma City, OK USA. [James, Judith A.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. RI Bachmann, Michael/E-8850-2010; Feldmann, Anja/D-7843-2014 OI Bachmann, Michael/0000-0002-8029-5755; Feldmann, Anja/0000-0001-5099-2448 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 1641 BP S696 EP S696 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359204105 ER PT J AU Lee, P Sykes, D Ameri, S Kalaitzidis, D Nigrovic, PA Cardona, A AF Lee, Pui Sykes, David Ameri, Sarah Kalaitzidis, Demetrios Nigrovic, Peter A. Cardona, Astrid TI Distinct Pathways Of Ly6C(hi) Monocyte Development Identified By a Novel Dual-Reporter Murine Myeloid Progenitor Cell Line SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Lee, Pui; Nigrovic, Peter A.] Boston Childrens Hosp, Boston, MA USA. [Sykes, David; Kalaitzidis, Demetrios] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ameri, Sarah] Brigham & Womens Hosp, Boston, MA 02115 USA. [Cardona, Astrid] Univ Texas San Antonio, San Antonio, 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 1142 BP S485 EP S485 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359203128 ER PT J AU Li, H Hsu, HC Wu, Q Li, J Yang, PA Fu, YX Mountz, JD AF Li, Hao Hsu, Hui-Chen Wu, Qi Li, Jun Yang, PingAr Fu, Yang-Xin Mountz, John D. TI Follicular Entry Of Lymphotoxin-Expressing B Cells Via Type I Interferon Disrupts Marginal Zone Barrier Integrity and Exacerbates Systemic Autoimmunity SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Li, Hao; Wu, Qi; Li, Jun; Yang, PingAr; Mountz, John D.] Univ Alabama Birmingham, Birmingham, AL USA. [Hsu, Hui-Chen] Birmingham VA Med Ctr, Birmingham, AL USA. [Fu, Yang-Xin] Univ Chicago, Chicago, IL 60637 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 37 BP S15 EP S16 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359201037 ER PT J AU Li, H Ice, JA Kelly, JA Adrianto, I Glenn, SB Hefner, KS Vista, EG Stone, DU Gopalakrishnan, R Houston, GD Lewis, DM Rohrer, M Hughes, P Harley, JB Montgomery, CG Chodosh, J Lessard, JA Anaya, JM Segal, BM Rhodus, NL Radfar, L Scofield, RH Lessard, CJ Sivils, KL AF Li, He Ice, John A. Kelly, Jennifer A. Adrianto, Indra Glenn, Stuart B. Hefner, Kimberly S. Vista, Evan G. Stone, Donald U. Gopalakrishnan, Raj Houston, Glen D. Lewis, David M. Rohrer, Michael Hughes, Pamela Harley, John B. Montgomery, Courtney G. Chodosh, James Lessard, James A. Anaya, Juan-Manuel Segal, Barbara M. Rhodus, Nelson L. Radfar, Lida Scofield, R. Hal Lessard, Christopher J. Sivils, Kathy L. TI Identification Of a Sjogren's Syndrome-Associated Variant That Influences OAS1 Isoform Switching SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Li, He; Stone, Donald U.; Houston, Glen D.; Lewis, David M.; Lessard, Christopher J.] Univ Oklahoma Hlth Sci Ctr, Oklahoma City, OK USA. [Ice, John A.; Kelly, Jennifer A.; Adrianto, Indra; Glenn, Stuart B.; Montgomery, Courtney G.; Scofield, R. Hal; Sivils, Kathy L.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Hefner, Kimberly S.] Hefner Eye Care & Opt Ctr, Oklahoma City, OK USA. [Vista, Evan G.] Univ Santo Tomas, Taguig City, Philippines. [Gopalakrishnan, Raj; Rohrer, Michael; Hughes, Pamela; Rhodus, Nelson L.] Univ Minnesota, Minneapolis, MN USA. [Harley, John B.] US Dept Vet Affairs Med Ctr, Cincinnati, OH USA. [Chodosh, James] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Lessard, James A.] Valley Bone & Joint Clin, Grand Forks, ND USA. [Anaya, Juan-Manuel] Univ Rosario, Sch Med & Hlth Sci, Bogota, Colombia. [Segal, Barbara M.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. RI Anaya, Juan-Manuel/J-1960-2016 OI Anaya, Juan-Manuel/0000-0002-6444-1249 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2772 BP S1185 EP S1186 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359206201 ER PT J AU Li, J Hsu, HC Yang, PA Wu, Q Luo, B Rowse, AL Spalding, DM Mobley, JA Bridges, SL Mountz, JD AF Li, Jun Hsu, Hui-Chen Yang, PingAr Wu, Qi Luo, Bao Rowse, Amber L. Spalding, David M. Mobley, James A. Bridges, S. Louis, Jr. Mountz, John D. TI Reshaping Inflammatory Macrophage Development and Functions by a Monosaccharide Analogue In Rheumatoid Arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Li, Jun; Yang, PingAr; Wu, Qi; Luo, Bao; Rowse, Amber L.; Spalding, David M.; Mobley, James A.; Bridges, S. Louis, Jr.; Mountz, John D.] Univ Alabama Birmingham, Birmingham, AL USA. [Hsu, Hui-Chen] Birmingham VA Med Ctr, Birmingham, AL 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2745 BP S1171 EP S1172 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359206174 ER PT J AU Liu, ML Bashir, M Sharma, M Xu, HH Williams, K Anyanwu, CO Okawa, J Werth, VP AF Liu, Ming-Lin Bashir, Muhammad Sharma, Meena Xu, Honghui Williams, Kevin Anyanwu, Cynthia O. Okawa, Joyce Werth, Victoria P. TI Novel Proinflammatory Microvesicles That Carry LL-37 In Patients With Cutaneous Lupus SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Liu, Ming-Lin; Sharma, Meena] Univ Penn, Philadelphia, PA 19104 USA. [Bashir, Muhammad; Xu, Honghui; Okawa, Joyce] Philadelphia VA Hosp, Philadelphia, PA USA. [Williams, Kevin] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [Anyanwu, Cynthia O.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Werth, Victoria P.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 1860 BP S793 EP S793 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359204319 ER PT J AU Michalk, I Berndt, N Bippes, CC Bartsch, H Koristka, S Arndt, C Feldmann, A Kurien, BT Scofield, RH Farris, AD James, JA Cartellieri, M Bachmann, M AF Michalk, Irene Berndt, Nicole Bippes, Claudia C. Bartsch, Holger Koristka, Stefanie Arndt, Claudia Feldmann, Anja Kurien, Biji T. Scofield, Robert Hal Farris, A. Darise James, Judith A. Cartellieri, Marc Bachmann, Michael TI Redox Dependent Conformational Changes Of The Autoantigen La Are Responsible For Its Shuttling, Translocation and a Pathophysiological Role Of Anti-La Autoantibodies SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Michalk, Irene; Berndt, Nicole; Bippes, Claudia C.; Bartsch, Holger; Koristka, Stefanie; Arndt, Claudia; Feldmann, Anja; Cartellieri, Marc; Bachmann, Michael] Carl Gustav Carus TU Dresden, Dresden, Germany. [Kurien, Biji T.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Scofield, Robert Hal] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Oklahoma City, OK 73104 USA. [Scofield, Robert Hal] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Scofield, Robert Hal] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Farris, A. Darise] Oklahoma Med Res Foun, Oklahoma City, OK USA. [James, Judith A.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. RI Bachmann, Michael/E-8850-2010; Feldmann, Anja/D-7843-2014 OI Bachmann, Michael/0000-0002-8029-5755; Feldmann, Anja/0000-0001-5099-2448 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 923 BP S396 EP S396 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359202428 ER PT J AU Miloslavsky, E Sullivan, A Richards, J McSparron, JI Roberts, D Puig, A AF Miloslavsky, Eli Sullivan, Amy Richards, Jeremy McSparron, Jakob I. Roberts, David Puig, Alberto TI The Resident-Fellow Interaction: Limiting Barriers and Maximizing Learning SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Miloslavsky, Eli] Massachusetts Gen Hopsital, Boston, MA USA. [Sullivan, Amy; Richards, Jeremy; Roberts, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [McSparron, Jakob I.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Puig, Alberto] 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2814 BP S1205 EP S1205 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359206243 ER PT J AU Miloslavsky, E Specks, U Merkel, PA Seo, P Spiera, RF Langford, CA Hoffman, GS Kallenberg, CGM St Clair, EW Tchao, N Ding, L Ikle, D Jepson, B Brunetta, P Stone, JH AF Miloslavsky, Eli Specks, Ulrich Merkel, Peter A. Seo, Philip Spiera, Robert F. Langford, Carol A. Hoffman, Gary S. Kallenberg, Cees G. M. St Clair, E. William Tchao, Nadia Ding, Linna Ikle, David Jepson, Brett Brunetta, Paul Stone, John H. TI Retreatment With Rituximab In The Rituximab In ANCA-Associated Vasculitis (RAVE) Trial SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Miloslavsky, Eli] Massachusetts Gen Hopsital, Boston, MA USA. [Specks, Ulrich] Mayo Clin, Rochester, MN USA. [Merkel, Peter A.] Univ Penn, Philadelphia, PA 19104 USA. [Merkel, Peter A.] VA Med Ctr, Philadelphia, PA USA. [Seo, Philip] Johns Hopkins Vasculitis Ctr, Baltimore, MD USA. [Spiera, Robert F.] Hosp Special Surg, New York, NY 10021 USA. [Langford, Carol A.] Cleveland Clin, Cleveland, OH 44106 USA. [Hoffman, Gary S.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Kallenberg, Cees G. M.] Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [St Clair, E. William] Duke Unvers Med Ctr, Durham, NC USA. [Tchao, Nadia] Immune Tolerance Network, Bethesda, MD USA. [Ding, Linna] NIAID, Bethesda, MD 20892 USA. [Ikle, David; Jepson, Brett] Rho, Chapel Hill, NC USA. [Brunetta, Paul] Genentech Inc, So San Francisco, CA USA. [Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2782 BP S1190 EP S1190 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359206211 ER PT J AU Miloslavsky, E Specks, U Merkel, PA Seo, P Spiera, RF Langford, CA Hoffman, GS Kallenberg, CGM St Clair, EW Tchao, N Ding, LN Ikle, D Jepson, B Brunetta, P Stone, JH AF Miloslavsky, Eli Specks, Ulrich Merkel, Peter A. Seo, Philip Spiera, Robert F. Langford, Carol A. Hoffman, Gary S. Kallenberg, Cees G. M. St Clair, E. William Tchao, Nadia Ding, Linna Ikle, David Jepson, Brett Brunetta, Paul Stone, John H. TI Efficacy Of Glucocorticoids To Treat Limited Flares In ANCA-Associated Vasculitis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Miloslavsky, Eli] Massachusetts Gen Hopsital, Boston, MA USA. [Specks, Ulrich] Mayo Clin, Rochester, MN USA. [Merkel, Peter A.] Univ Penn, Philadelphia, PA 19104 USA. [Seo, Philip] Johns Hopkins Vasculitis Ctr, Baltimore, MD USA. [Spiera, Robert F.] Hosp Special Surg, New York, NY 10021 USA. [Langford, Carol A.] Cleveland Clin, Cleveland, OH 44106 USA. [Hoffman, Gary S.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Kallenberg, Cees G. M.] Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [St Clair, E. William] Duke Univ, Med Ctr, Durham, NC USA. [Tchao, Nadia] Immune Tolerance Network, Bethesda, MD USA. [Ding, Linna] NIAID, Bethesda, MD 20892 USA. [Ikle, David; Jepson, Brett] Rho, Chapel Hill, NC USA. [Brunetta, Paul] Genentech Inc, So San Francisco, CA USA. [Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 747 BP S315 EP S316 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359202252 ER PT J AU Miloslavsky, E Specks, U Merkel, PA Seo, P Spiera, RF Langford, CA Hoffman, GS Kallenberg, CGM St Clair, EW Tchao, N Ding, LN Ikle, D Jepson, B Brunetta, P Stone, JH AF Miloslavsky, Eli Specks, Ulrich Merkel, Peter A. Seo, Philip Spiera, Robert F. Langford, Carol A. Hoffman, Gary S. Kallenberg, Cees G. M. St Clair, E. William Tchao, Nadia Ding, Linna Ikle, David Jepson, Brett Brunetta, Paul Stone, John H. TI Safety Of Remission Induction With Rituximab Versus Cyclosphosphamide In Patients 65 and Older With Severe ANCA-Associated Vasculitis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Miloslavsky, Eli; Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Specks, Ulrich] Mayo Clin, Rochester, MN USA. [Merkel, Peter A.] Univ Penn, Philadelphia, PA 19104 USA. [Merkel, Peter A.] VA Med Ctr, Philadelphia, PA USA. [Seo, Philip] Johns Hopkins Vasculitis Ctr, Baltimore, MD USA. [Spiera, Robert F.] Hosp Special Surg, New York, NY 10021 USA. [Langford, Carol A.] Cleveland Clin, Cleveland, OH 44106 USA. [Hoffman, Gary S.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Kallenberg, Cees G. M.] Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [St Clair, E. William] Duke Univ, Med Ctr, Durham, NC USA. [Tchao, Nadia] Immune Tolerance Network, Bethesda, MD USA. [Ding, Linna] NIAID, Bethesda, MD 20892 USA. [Ikle, David; Jepson, Brett] Rho, Chapel Hill, NC USA. [Brunetta, Paul] Genentech Inc, So San Francisco, CA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 742 BP S313 EP S313 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359202247 ER PT J AU Ritter, SY Greenblatt, MB Tsang, K Hu, DZ Wright, J Aliprantis, AO AF Ritter, Susan Y. Greenblatt, Matthew B. Tsang, Kelly Hu, Dorothy Z. Wright, John Aliprantis, Antonios O. TI Spontaneous Osteoarthritis In Mice By Genetic Deletion Of Nfatc1 and Nfatc2 SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Ritter, Susan Y.; Greenblatt, Matthew B.; Tsang, Kelly; Wright, John; Aliprantis, Antonios O.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hu, Dorothy Z.] 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2733 BP S1166 EP S1167 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359206162 ER PT J AU Ruth, NM Kral, MC Nowling, TK Slan, S Passo, MH Gilkeson, GS AF Ruth, Natasha M. Kral, Mary C. Nowling, Tamara K. Slan, Stephanie Passo, Murray H. Gilkeson, Gary S. TI The Usefulness Of Traditional Neurocognitive Testing and N-Methyl-D-Aspartate Receptor Antibodies In Pediatric Lupus Patients SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Ruth, Natasha M.; Kral, Mary C.; Nowling, Tamara K.; Slan, Stephanie; Passo, Murray H.; Gilkeson, Gary S.] Med Univ S Carolina, Charleston, SC 29425 USA. [Nowling, Tamara K.] Ralph H Johnson VA Med Ctr, Charleston, SC 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 1261 BP S533 EP S533 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359203244 ER PT J AU Sato, S Williams, S Karam, E Zhang, X AF Sato, Shuzo Williams, Sarah Karam, Eva Zhang, Xian TI Fli-1 Regulates Immune Cell Infiltration Through Affecting Local Chemokine Expression and IL-6 Expression In The Kidney Of Lupus Prone Mice SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Sato, Shuzo; Karam, Eva; Zhang, Xian] Med Univ S Carolina, Charleston, SC 29425 USA. [Williams, Sarah; Zhang, Xian] Ralph H Johnson VA Med Ctr, Charleston, SC 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 558 BP S242 EP S242 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359202070 ER PT J AU Schmajuk, G Yazdany, J Miao, YH Daikh, DI Steinman, M AF Schmajuk, Gabriela Yazdany, Jinoos Miao, Yinghui Daikh, David I. Steinman, Michael TI Folic Acid Prescription Among Older Adult Methotrexate Initiators Is Poor SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Schmajuk, Gabriela] UCSF San Francisco VA Med Ctr, San Francisco, CA USA. [Yazdany, Jinoos; Daikh, David I.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Miao, Yinghui; Steinman, Michael] San Francisco VA Med Ctr, San Francisco, CA 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 1711 BP S725 EP S725 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359204171 ER PT J AU Singh, JA Bharat, A Khanna, P Aquino-Beaton, C Persselin, JE Duffy, E Elashoff, D Khanna, D AF Singh, Jasvinder A. Bharat, Aseem Khanna, Puja Aquino-Beaton, Cleopatra Persselin, Jay E. Duffy, Erin Elashoff, David Khanna, Dinesh TI Health Care Utilization In Gout Patients: A Prospective Multicenter Cohort Study SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Singh, Jasvinder A.] Univ Alabama, Tuscaloosa, AL USA. [Bharat, Aseem] Univ Alabama Birmingham, Birmingham, AL USA. [Khanna, Puja] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [Aquino-Beaton, Cleopatra; Persselin, Jay E.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Duffy, Erin] Univ Calif Los Angeles, Los Angeles, CA USA. [Elashoff, David] Univ Calif Los Angeles, Dept Med, Stat Core, Los Angeles, CA 90024 USA. [Khanna, Dinesh] 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 1997 BP S852 EP S853 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359204455 ER PT J AU Unizony, S Stone, J Keroack, B AF Unizony, Sebastian Stone, John Keroack, Brian TI Long-Term Use Of Tocilizumab For The Treatment Of Giant Cell Arteritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Unizony, Sebastian; Stone, John] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Keroack, Brian] Tufts Univ, Sch Med, Maine Med Ctr, Maine, ME 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 1685 BP S713 EP S713 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359204147 ER PT J AU Vina, ER Utset, TO Hannon, MJ Roberts, N Masi, CM Kwoh, CK AF Vina, Ernest R. Utset, Tammy O. Hannon, Michael J. Roberts, Nicole Masi, Christopher M. Kwoh, C. Kent TI Racial Differences In Systemic Lupus Erythematosus Patients' Treatment Preferences: A Two-Site Study SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Vina, Ernest R.; Kwoh, C. Kent] Univ Pittsburgh, Pittsburgh, PA USA. [Vina, Ernest R.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Utset, Tammy O.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Hannon, Michael J.; Roberts, Nicole] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Masi, Christopher M.] NorthShore Univ Hlth Syst, Evanston, IL 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 1069 BP S456 EP S457 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359203055 ER PT J AU Wallace, ZS Mahajan, V Carruthers, M Mattoo, H Pillai, S Stone, JH AF Wallace, Zachary S. Mahajan, Vinay Carruthers, Mollie Mattoo, Hamid Pillai, Shiv Stone, John H. TI Elevated IgG4+Plasmablasts In Patients With Active, Untreated IgG4-Related Disease SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Wallace, Zachary S.; Carruthers, Mollie; Pillai, Shiv; Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mahajan, Vinay; Mattoo, Hamid] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2024 BP S863 EP S864 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359204482 ER PT J AU Wallace, ZS Deshpande, V Stone, JH AF Wallace, Zachary S. Deshpande, Vikram Stone, John H. TI Ophthalmic Manifestations Of IgG4-Related Disease: A Single-Center Experience. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Wallace, Zachary S.; Deshpande, Vikram; Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 785 BP S332 EP S333 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359202290 ER PT J AU Werth, VP Khamashta, MA Illei, GG Yoo, S Wang, LW Greth, W AF Werth, Victoria P. Khamashta, Munther A. Illei, Gabor G. Yoo, Stephen Wang, Liangwei Greth, Warren TI Smoking Is Associated With More Severe Skin Disease In Subjects With Moderate To Severe Systemic Lupus Erythematosus (SLE) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Werth, Victoria P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Khamashta, Munther A.] Kings Coll London, Sch Med, Rayne Inst, Lupus Res Unit, London, England. [Illei, Gabor G.; Yoo, Stephen; Wang, Liangwei; Greth, Warren] MedImmune LLC, Gaithersburg, MD 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2512 BP S1072 EP S1073 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359205457 ER PT J AU Werth, VP Fiorentino, D Cohen, SB Fivenson, D Hansen, C Zoog, S Arnold, G Wang, C Boedigheimer, M Welcher, A Chung, J Sullivan, B Martin, DA AF Werth, Victoria P. Fiorentino, David Cohen, Stanley B. Fivenson, David Hansen, Chris Zoog, Steve Arnold, Greg Wang, Christine Boedigheimer, Michael Welcher, Andrew Chung, James Sullivan, Barbara Martin, David A. TI A Phase I Single-Dose Crossover Study To Evaluate The Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Efficacy Of AMG 811 (anti-IFN-gamma) In Subjects With Discoid Lupus Erythematosus SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Werth, Victoria P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Fiorentino, David] Stanford Univ, Sch Med, Redwood City, CA USA. [Cohen, Stanley B.] Metroplex Clin Res Ctr, Dallas, TX USA. [Fivenson, David] Dermatology PLLC, MD, Ann Arbor, MI USA. [Hansen, Chris] Univ Utah, Sch Med, Salt Lake City, UT USA. [Zoog, Steve; Arnold, Greg; Wang, Christine; Boedigheimer, Michael; Welcher, Andrew; Chung, James; Sullivan, Barbara] Amgen Inc, Thousand Oaks, CA USA. [Martin, David A.] Amgen Inc, Seattle, WA USA. NR 0 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 1608 BP S682 EP S683 PG 2 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359204072 ER PT J AU Yang, WH Bloch, EG Berenson, DF Galdos, RL Arora, P Wu, CN Bloch, DB AF Yang, Wei-Hong Bloch, Emily G. Berenson, Daniel F. Galdos, Rita L. Arora, Pankaj Wu, Connie Bloch, Donald B. TI The Use Of "Autoantigenomics" To Rapidly Identify Targets Of Human Autoantibodies SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 158 BP S63 EP S63 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359201157 ER PT J AU Young, K Benissan-Messan, D Duryee, MJ Anderson, D Caplan, L Davis, LA Sayles, H Hunter, CD Klassen, LW O'Dell, JR Mikuls, TR Thiele, GM AF Young, Kathleen Benissan-Messan, Dathe Duryee, Michael J. Anderson, Daniel Caplan, Liron Davis, Lisa A. Sayles, Harlan Hunter, Carlos D. Klassen, Lynell W. O'Dell, James R. Mikuls, Ted R. Thiele, Geoffrey M. TI Antibody To Malondialdehyde-Acetaldehyde Adducts (MAA) Is a Biomarker Of Inflammation and Is Correlated With The Disease Activity In Rheumatoid SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Young, Kathleen; Benissan-Messan, Dathe; Duryee, Michael J.; Anderson, Daniel; Sayles, Harlan; Hunter, Carlos D.; Klassen, Lynell W.; O'Dell, James R.; Mikuls, Ted R.; Thiele, Geoffrey M.] Univ Nebraska Med Ctr, Omaha, NE USA. [Caplan, Liron] Denver Vet Affairs Med Ctr, Denver, CO USA. [Davis, Lisa A.] Denver Hlth & Hosp Author, Denver, CO USA. [Klassen, Lynell W.; Thiele, Geoffrey M.] Omaha VA Med Ctr, Omaha, NE USA. [Mikuls, Ted R.] Omaha VA, Omaha, NE 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2262 BP S962 EP S962 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359205209 ER PT J AU Zhao, J Giles, BM Taylor, RL Yette, GA Lough, KM Abraham, LJ Wu, H Gaffney, PM Kelly, JA Kaufman, KM Harley, JB Langefeld, CD Brown, EE Edberg, JC Kimberly, RP Ulgiati, D Tsao, BP Boackle, SA AF Zhao, Jian Giles, Brendan M. Taylor, Rhonda L. Yette, Gabriel A. Lough, Kara M. Abraham, Lawrence J. Wu, Hui Gaffney, Patrick M. Kelly, Jennifer A. Kaufman, Kenneth M. Harley, John B. Langefeld, Carl D. Brown, Elizabeth E. Edberg, Jeffrey C. Kimberly, Robert P. Ulgiati, Daniela Tsao, Betty P. Boackle, Susan A. TI An Intronic CR2 Polymorphism Associated With Systemic Lupus Erythematosus Alters CTCF Binding and CR1 Expression SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 77th Annual Meeting of the American-College-of-Rheumatology / 48th Annual Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 25-30, 2013 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Zhao, Jian; Wu, Hui; Tsao, Betty P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Giles, Brendan M.; Yette, Gabriel A.; Lough, Kara M.; Boackle, Susan A.] Univ Colorado, Sch Med, Aurora, CO USA. [Taylor, Rhonda L.; Abraham, Lawrence J.; Ulgiati, Daniela] Univ Western Australia, Perth, WA 6009, Australia. [Gaffney, Patrick M.; Kelly, Jennifer A.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Kaufman, Kenneth M.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Kaufman, Kenneth M.] Univ Cincinnati, Cincinnati, OH USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Langefeld, Carl D.] Wake Forest Sch Med, Winston Salem, NC USA. [Brown, Elizabeth E.; Kimberly, Robert P.] Univ Alabama Birmingham, Birmingham, AL USA. [Edberg, Jeffrey C.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 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 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2013 VL 65 SU 10 SI SI MA 2703 BP S1155 EP S1155 PG 1 WC Rheumatology SC Rheumatology GA 230RF UT WOS:000325359206133 ER PT J AU Caplan, D Michaud, J Hufford, R AF Caplan, David Michaud, Jennifer Hufford, Rebecca TI Dissociations and associations of performance in syntactic comprehension in aphasia and their implications for the nature of aphasic deficits SO BRAIN AND LANGUAGE LA English DT Article DE Aphasia; Syntactic comprehension; Task effects; Deficits ID SPOKEN-LANGUAGE COMPREHENSION; MOVING-WINDOW TECHNIQUE; SENTENCE COMPREHENSION; BROCAS APHASIA; CAPACITY THEORY; WORKING-MEMORY; STROKE APHASIA; EYE-MOVEMENTS; MODEL; DETERMINANTS AB Sixty-one pwa were tested on syntactic comprehension in three tasks: sentence-picture matching, sentence-picture matching with auditory moving window presentation, and object manipulation. There were significant correlations of performances on sentences across tasks. First factors on which all sentence types loaded in unrotated factor analyses accounted for most of the variance in each task. Dissociations in performance between sentence types that differed minimally in their syntactic structures were not consistent across tasks. These results replicate previous results with smaller samples and provide important validation of basic aspects of aphasic performance in this area of language processing. They point to the role of a reduction in processing resources and of the interaction of task demands and parsing and interpretive abilities in the genesis of patient performance. (C) 2013 Elsevier Inc. All rights reserved. C1 [Caplan, David; Michaud, Jennifer; Hufford, Rebecca] Massachusetts Gen Hosp, Neuropsychol Lab, Dept Neurol, Boston, MA 02114 USA. RP Caplan, D (reprint author), Neuropsychol Lab, 175 Cambridge St,Suite 340,Fruit St, Boston, MA 02114 USA. EM dcaplan@partners.org FU NIDCD [DC00942] FX This research was supported by NIDCD Grant DC00942 to David Caplan. NR 58 TC 13 Z9 13 U1 6 U2 27 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X EI 1090-2155 J9 BRAIN LANG JI Brain Lang. PD OCT PY 2013 VL 127 IS 1 BP 21 EP 33 DI 10.1016/j.bandl.2013.07.007 PG 13 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 242BV UT WOS:000326213300004 PM 24061104 ER PT J AU Yoshizawa, JM Schafer, CA Schafer, JJ Farrell, JJ Paster, BJ Wong, DTW AF Yoshizawa, Janice M. Schafer, Christopher A. Schafer, Jason J. Farrell, James J. Paster, Bruce J. Wong, David T. W. TI Salivary Biomarkers: Toward Future Clinical and Diagnostic Utilities SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID MICROBE IDENTIFICATION MICROARRAY; SQUAMOUS-CELL CARCINOMA; ORAL-CANCER DETECTION; PANCREATIC-CANCER; BACTERIAL DIVERSITY; PROMOTER HYPERMETHYLATION; REFRACTORY PERIODONTITIS; STREPTOCOCCUS-MUTANS; HEALTHY-INDIVIDUALS; FLUID SPECIMENS AB The pursuit of timely, cost-effective, accurate, and noninvasive diagnostic methodologies is an endeavor of urgency among clinicians and scientists alike. Detecting pathologies at their earliest stages can significantly affect patient discomfort, prognosis, therapeutic intervention, survival rates, and recurrence. Diagnosis and monitoring often require painful invasive procedures such as biopsies and repeated blood draws, adding undue stress to an already unpleasant experience. The discovery of saliva-based microbial, immunologic, and molecular biomarkers offers unique opportunities to bypass these measures by utilizing oral fluids to evaluate the condition of both healthy and diseased individuals. Here we discuss saliva and its significance as a source of indicators for local, systemic, and infectious disorders. We highlight contemporary innovations and explore recent discoveries that deem saliva a mediator of the body's physiological condition. Additionally, we examine the current state of salivary diagnostics and its associated technologies, future aspirations, and potential as the preferred route of disease detection, monitoring, and prognosis. C1 [Yoshizawa, Janice M.; Schafer, Christopher A.; Wong, David T. W.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. [Yoshizawa, Janice M.; Schafer, Christopher A.; Wong, David T. W.] Ctr Oral Head & Neck Oncol Res, Los Angeles, CA 90024 USA. [Schafer, Jason J.] Thomas Jefferson Univ, Jefferson Sch Pharm, Dept Pharm Practice, Philadelphia, PA 19107 USA. [Farrell, James J.] Yale Univ, Sch Med, Yale Ctr Pancreat Dis & Endoscop Oncol, New Haven, CT USA. [Paster, Bruce J.] Forsyth Inst, Cambridge, MA USA. [Paster, Bruce J.] Harvard Univ, Sch Dent Med, Dept Oral Biol Med, Boston, MA 02115 USA. RP Wong, DTW (reprint author), Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. EM dtww@ucla.edu FU NIDCR NIH HHS [T90 DE022734] NR 120 TC 45 Z9 47 U1 4 U2 53 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0893-8512 EI 1098-6618 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD OCT PY 2013 VL 26 IS 4 BP 781 EP 791 DI 10.1128/CMR.00021-13 PG 11 WC Microbiology SC Microbiology GA 229NF UT WOS:000325272500006 PM 24092855 ER PT J AU Rahman, M Baimbridge, C Davis, BR Barzilay, JI Basile, JN Henriquez, MA Huml, A Kopyt, N Louis, GT Pressel, SL Rosendorr, C Sastrasinh, S Stanford, C AF Rahman, Mahboob Baimbridge, Charles Davis, Barry R. Barzilay, Joshua I. Basile, Jan N. Henriquez, Mario A. Huml, Anne Kopyt, Nelson Louis, Gail T. Pressel, Sara L. Rosendorr, Clive Sastrasinh, Sithiporn Stanford, Carol CA ALLHAT Collaborative Res Grp TI Pravastatin and cardiovascular outcomes stratified by baseline eGFR in the lipid-lowering component of ALLHAT SO CLINICAL NEPHROLOGY LA English DT Article DE hyperlipidemia; kidney disease; cardiovascular outcomes; chronic renal failure ID CHRONIC KIDNEY-DISEASE; CHRONIC RENAL-INSUFFICIENCY; GLOMERULAR-FILTRATION-RATE; ATTACK TRIAL ALLHAT; USUAL CARE; EVENTS; HEART; ATORVASTATIN; HEMODIALYSIS; CHOLESTEROL AB Background/Aims: The role of statins in preventing cardiovascular outcomes in patients with chronic kidney disease (CKD) is unclear. This paper compares cardiovascular outcomes with pravastatin vs. usual care, stratified by baseline estimated glomerular filtration rate (eGFR). Methods: Post-hoc analyses of a prospective randomized open-label clinical trial; 10,151 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (lipid-lowering component) were randomized to pravastatin 40 mg/day or usual care. Mean follow-up was 4.8 years. Results: Through Year 6, total cholesterol declined in pravastatin (-20.7%) and usual-care groups (-11.2%). Use of statin therapy in the pravastatin group was 89.8% (Year 2) and 87.0% (Year 6). Usual-care group statin use increased from 8.2% (Year 2) to 23.5% (Year 6). By primary intention-to-treat analyses, no significant differences were seen between groups for coronary heart disease (CHD), total mortality or combined cardiovascular disease; findings were consistent across eGFR strata. In exploratory "as-treated" analyses (patients actually using pravastatin vs. not using), pravastatin therapy was associated with lower mortality (HR = 0.76 (0.68 - 0.85), p < 0.001) and lower CHID (HR = 0.84 (0.73 - 0.97), p = 0.01), but not combined cardiovascular disease (HR = 0.95 (0.88 - 1.04), p = 0.30). Total cholesterol reduction of 10 mg/dL from baseline to Year 2 was associated with 5% lower CHD risk. Conclusions: In hypertensive patients with moderate dyslipidemia, pravastatin was not superior to usual care in preventing total mortality or CHD independent of baseline eGFR level. However, exploratory "as-treated" analyses suggest improved mortality and CHD risk in participants using pravastatin, and decreased CHD events associated with achieved reduction in total cholesterol. Potential benefit from statin therapy may depend on degree of reduction achieved in total and LDL-cholesterol and adherence to therapy. C1 [Rahman, Mahboob; Huml, Anne] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Louis Stokes Cleveland Vet Affairs Med Ctr, Cleveland, OH 44106 USA. [Baimbridge, Charles; Davis, Barry R.; Pressel, Sara L.] Univ Texas Houston, Sch Publ Hlth, Houston, TX 77030 USA. [Barzilay, Joshua I.] Kaiser Permanente Georgia, Tucker, GA USA. [Basile, Jan N.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Henriquez, Mario A.] Bronx Nephrol Hypertens, Bronx, NY USA. [Kopyt, Nelson] Lehigh Valley Hosp, Allentown, PA USA. [Louis, Gail T.] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA 70118 USA. [Rosendorr, Clive] Mt Sinai Sch Med, New York, NY USA. [Rosendorr, Clive] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Sastrasinh, Sithiporn] Vet Affairs New Jersey Hlth Care Syst, E Orange, NJ USA. [Stanford, Carol] Univ Missouri, Sch Med, Kansas City, MO 64108 USA. RP Pressel, SL (reprint author), Univ Texas Houston, Sch Publ Hlth, Coordinating Ctr Clin Trials, 1200 Herman Pressler St,Suite W908, Houston, TX 77030 USA. EM Sara.L.Pressel@uth.tmc.edu FU National Heart, Lung, and Blood Institute [NO1-HC-35130]; Pfizer FX This study was supported by contract NO1-HC-35130 with the National Heart, Lung, and Blood Institute. The ALLHAT investigators acknowledge contributions of study medications supplied by Pfizer (amlodipine and doxazosin), AstraZeneca (atenolol and lisinopril) and Bristol-Myers Squibb (pravastatin), and financial support provided by Pfizer. NR 23 TC 2 Z9 2 U1 0 U2 4 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD OCT PY 2013 VL 80 IS 4 BP 235 EP 248 DI 10.5414/CN107922 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA 241YS UT WOS:000326205200001 PM 23816477 ER PT J AU Kang, RW Mahony, GT Harris, TC Dines, JS AF Kang, Richard W. Mahony, Gregory T. Harris, Thomas C. Dines, Joshua S. TI Posterior Instability Caused by Batter's Shoulder SO CLINICS IN SPORTS MEDICINE LA English DT Article DE Posterior instability; Posterior labral repair; Batter's shoulder; Shoulder injury ID SUBLUXATION; BASEBALL; LESION; REPAIR AB The lead shoulder of a batter's swing can undergo tremendous forces, especially when a pitch is missed. Repetitive loads on the shoulder in this setting can lead to posterior instability also known as batter's shoulder. This article reviews the pathomechanics, clinical presentation, imaging, treatment options, and initial clinical results of batter's shoulder. C1 [Kang, Richard W.; Mahony, Gregory T.; Dines, Joshua S.] Hosp Special Surg, Dept Sports Med & Shoulder Surg, New York, NY 10021 USA. [Harris, Thomas C.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Kang, RW (reprint author), Hosp Special Surg, Dept Sports Med & Shoulder Surg, 535 E 70th St, New York, NY 10021 USA. EM rwkang.md@gmail.com NR 13 TC 2 Z9 2 U1 2 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-5919 EI 1556-228X J9 CLIN SPORT MED JI Clin. Sports Med. PD OCT PY 2013 VL 32 IS 4 BP 797 EP + DI 10.1016/j.csm.2013.07.012 PG 7 WC Sport Sciences SC Sport Sciences GA 243GW UT WOS:000326305900014 PM 24079435 ER PT J AU Gwathmey, FW Warner, JJP AF Gwathmey, F. Winston, Jr. Warner, Jon J. P. TI Management of the Athlete with a Failed Shoulder Instability Procedure SO CLINICS IN SPORTS MEDICINE LA English DT Article DE Shoulder instability; Recurrence; Athlete; Bankart; Latarjet ID ARTHROSCOPIC BANKART REPAIR; GLENOID BONE LOSS; ANTERIOR GLENOHUMERAL INSTABILITY; HILL-SACHS LESION; 6-YEAR FOLLOW-UP; LATARJET PROCEDURE; SUTURE-ANCHOR; RISK-FACTORS; SURGICAL-TREATMENT; EXTERNAL ROTATION AB Athletes often expose their shoulders to significant forces and stresses and treatment of recurrent shoulder instability in this population is challenging. Recurrence after surgical shoulder stabilization in an athlete warrants a systematic approach to the diagnosis and treatment, The surgeon must develop a dear understanding of the etiology of the failure and take the necessary steps during the management algorithm to prevent a subsequent recurrence. When planning revision surgical stabilization, the surgeon must analyze and address risk factors for recurrence, which include younger age, contact/collision sports, higher level of competition, capsular laxity, glenoid bone loss, and engaging Hill-Sachs deformities. The surgeon must provide the athlete with the surgery that provides the best chance to return to sport and the lowest risk of recurrent instability. While revision arthroscopic Bankart repair may be appropriate in some cases in which there is minimal glenoid bone loss and robust labral and capsular tissue is available, an open procedure such as a Latarjet may be indicated for athletes at high risk for recurrence. C1 [Gwathmey, F. Winston, Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Warner, Jon J. P.] Harvard Univ, Sch Med, MGH Shoulder Serv, Boston Shoulder Inst,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Warner, JJP (reprint author), Harvard Univ, Sch Med, MGH Shoulder Serv, Boston Shoulder Inst,Massachusetts Gen Hosp, 55 Fruit St,Suite 3200, Boston, MA 02114 USA. EM jwarner@partners.org NR 127 TC 2 Z9 2 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-5919 EI 1556-228X J9 CLIN SPORT MED JI Clin. Sports Med. PD OCT PY 2013 VL 32 IS 4 BP 833 EP + DI 10.1016/j.csm.2013.07.016 PG 33 WC Sport Sciences SC Sport Sciences GA 243GW UT WOS:000326305900018 PM 24079439 ER PT J AU Grottkau, BE Cai, XX Wang, J Yang, XM Lin, YF AF Grottkau, Brian E. Cai, Xiaoxiao Wang, Jing Yang, Xingmei Lin, Yunfeng TI Polymeric Nanoparticles for a Drug Delivery System SO CURRENT DRUG METABOLISM LA English DT Article DE Polymeric nanoparticles; PHA; PLGA ID PEG-PLGA NANOPARTICLES; IN-VITRO EVALUATION; BIODEGRADABLE NANOPARTICLES; TARGETED NANOMEDICINES; VIVO EVALUATION; MODEL PROTEIN; MICROSPHERES; TISSUE; POLYHYDROXYALKANOATES; BIOCOMPATIBILITY AB In recent years, nanotechnology research has made great strides in the area of pharmacy, especially for drug delivery systems. Polymeric nanoparticles provide significant stability in anti-neoplastic drug research and have demonstrated the ability to solve the problems of therapeutic efficacy and diagnostic sensitivity. In this review, we describe the specific advantages of polymeric nanoparticles and their applications for a drug delivery system. The latest research on PHA-based polymeric nanoparticles and PLGA is also discussed. C1 [Grottkau, Brian E.] Harvard Univ, Sch Med, MassGen Hosp Children, Dept Orthopaed Surg, Boston, MA USA. [Grottkau, Brian E.] Harvard Univ, Sch Med, Pediat Orthopaed Lab Tissue Engn & Regenerat Med, Boston, MA USA. [Cai, Xiaoxiao; Yang, Xingmei; Lin, Yunfeng] Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610041, Peoples R China. [Wang, Jing] Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Dept Stomatol, Shanghai 200092, Peoples R China. RP Lin, YF (reprint author), Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, 14,3rd Sec,Ren Min Nan Rd, Chengdu 610041, Peoples R China. EM yunfenglin@scu.edu.cn RI Lin, Yunfeng/M-5438-2013; Lin, Yunfeng/H-3393-2011; OI Lin, Yunfeng/0000-0003-1224-6561; Lin, Yunfeng/0000-0003-1224-6561; Cai, Xiaoxiao/0000-0002-5654-7414 FU National Natural Science Foundation of China [81071273, 31170929, 81201211]; Foundation for the Author of National Excellent Doctoral Dissertation of China [FANEDD 200977]; Doctoral Fund of Ministry of Education of China [20110181120071] FX This work was funded by National Natural Science Foundation of China (81071273, 31170929, 81201211), Foundation for the Author of National Excellent Doctoral Dissertation of China (FANEDD 200977), Doctoral Fund of Ministry of Education of China (20110181120071). NR 50 TC 12 Z9 12 U1 10 U2 61 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2002 EI 1875-5453 J9 CURR DRUG METAB JI Curr. Drug Metab. PD OCT PY 2013 VL 14 IS 8 SI SI BP 840 EP 846 PG 7 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 241LR UT WOS:000326168900004 PM 24016112 ER PT J AU Uygun, BE Yarmush, ML AF Uygun, Basak E. Yarmush, Martin L. TI Engineered liver for transplantation SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID PLURIPOTENT STEM-CELLS; HEPATOCYTE TRANSPLANTATION; EXTRACELLULAR-MATRIX; REGENERATIVE MEDICINE; STEM/PROGENITOR CELLS; DECELLULARIZED MATRIX; UNITED-STATES; FETAL LIVER; TISSUE; SCAFFOLDS AB Orthotopic liver transplantation is the only definitive treatment for end stage liver failure and the shortage of donor organs severely limits the number of patients receiving transplants. Liver tissue engineering aims to address the donor liver shortage by creating functional tissue constructs to replace a damaged or failing liver. Despite decades of work, various bottoms-up, synthetic biomaterials approaches have failed to produce a functional construct suitable for transplantation. Recently, a new strategy has emerged using whole organ scaffolds as a vehicle for tissue engineering. This technique involves preparation of these organ scaffolds via perfusion decellularization with the resulting scaffold retaining the circulatory network of the native organ. This important phenomenon allows for the construct to be repopulated with cells and to be connected to the blood torrent upon transplantation. This opinion paper presents the current advances and discusses the challenges of creating fully functional transplantable liver grafts with this whole liver engineering approach. C1 [Uygun, Basak E.; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. [Uygun, Basak E.; Yarmush, Martin L.] Shriners Hosp Children Boston, Boston, MA 02114 USA. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. RP Yarmush, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org RI Uygun, Basak/I-1792-2012 OI Uygun, Basak/0000-0002-2600-7900 FU NIDDK NIH HHS [K99 DK088962, R00 DK088962, R01 DK084053] NR 66 TC 12 Z9 13 U1 3 U2 41 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 EI 1879-0429 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD OCT PY 2013 VL 24 IS 5 BP 893 EP 899 DI 10.1016/j.copbio.2013.05.008 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 241BP UT WOS:000326141700011 PM 23791465 ER PT J AU Tegos, GP Hamblin, MR AF Tegos, George P. Hamblin, Michael R. TI Disruptive innovations: new anti-infectives in the age of resistance SO CURRENT OPINION IN PHARMACOLOGY LA English DT Editorial Material C1 [Tegos, George P.] Univ New Mexico, Ctr Mol Discovery, Albuquerque, NM 87131 USA. [Tegos, George P.] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA. [Tegos, George P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tegos, George P.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Tegos, GP (reprint author), Univ New Mexico, Ctr Mol Discovery, Albuquerque, NM 87131 USA. EM gtegos@salud.unm.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [R01 AI050875, R01AI050875] NR 12 TC 8 Z9 9 U1 2 U2 19 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 EI 1471-4973 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD OCT PY 2013 VL 13 IS 5 BP 673 EP 677 DI 10.1016/j.coph.2013.08.012 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 241BD UT WOS:000326140500001 PM 24012294 ER PT J AU Bologa, CG Ursu, O Oprea, TI Melancon, CE Tegos, GP AF Bologa, Cristian G. Ursu, Oleg Oprea, Tudor I. Melancon, Charles E., III Tegos, George P. TI Emerging trends in the discovery of natural product antibacterials SO CURRENT OPINION IN PHARMACOLOGY LA English DT Article ID I POLYKETIDE SYNTHASES; ESCHERICHIA-COLI; GENE CLUSTERS; BIOSYNTHESIS; RESISTANCE; STREPTOMYCES; ANTIBIOTICS; BACTERIAL; INHIBITION; DIVERSITY AB This article highlights current trends and advances in exploiting natural sources for the deployment of novel and potent anti-infective countermeasures. The key challenge is to therapeutically target bacterial pathogens that exhibit a variety of puzzling and evolutionarily complex resistance mechanisms. Special emphasis is given to the strengths, weaknesses, and opportunities in the natural product antibacterial drug discovery arena, and to emerging applications driven by advances in bioinformatics, chemical biology, and synthetic biology in concert with exploiting bacterial phenotypes. These efforts have identified a critical mass of natural product antibacterial lead compounds and discovery technologies with high probability of successful implementation against emerging bacterial pathogens. C1 [Bologa, Cristian G.; Ursu, Oleg; Oprea, Tudor I.; Tegos, George P.] Univ New Mexico, Ctr Mol Discovery, Albuquerque, NM 87131 USA. [Bologa, Cristian G.; Ursu, Oleg; Oprea, Tudor I.] Univ New Mexico, Hlth Sci Ctr, Dept Internal Med, Translat Informat Div, Albuquerque, NM 87131 USA. [Oprea, Tudor I.] Univ Gothenburg, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden. [Oprea, Tudor I.] Tech Univ Denmark, Ctr Biol Sequence Anal, Dept Syst Biol, DK-2800 Lyngby, Denmark. [Melancon, Charles E., III] Univ New Mexico, Dept Chem & Biol Chem, Albuquerque, NM 87131 USA. [Melancon, Charles E., III] Univ New Mexico, Dept Biol, Albuquerque, NM 87131 USA. [Tegos, George P.] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA. [Tegos, George P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tegos, George P.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Melancon, CE (reprint author), Univ New Mexico, Dept Chem & Biol Chem, Albuquerque, NM 87131 USA. EM gtegos@salud.unm.edu RI Oprea, Tudor/A-5746-2011; Luan, Gan/B-3211-2015; Bologa, Cristian/A-7952-2010 OI Oprea, Tudor/0000-0002-6195-6976; Bologa, Cristian/0000-0003-2232-4244 FU NIH [5U54MH084690-02]; DTRA [HDTRA1-13-C-0005]; NCRR [5P20RR016480-12]; NIGMS [8P20GM103451-12] FX Work in the authors' laboratories was supported by the NIH (grant 5U54MH084690-02 to GPT), DTRA (contract number HDTRA1-13-C-0005 to GPT), NCRR (5P20RR016480-12 to CGB) and NIGMS (8P20GM103451-12 to CGB) NR 49 TC 14 Z9 14 U1 4 U2 45 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 EI 1471-4973 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD OCT PY 2013 VL 13 IS 5 BP 678 EP 687 DI 10.1016/j.coph.2013.07.002 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 241BD UT WOS:000326140500002 PM 23890825 ER PT J AU Yin, R Dai, TH Avci, P Jorge, AES de Melo, WCMA Vecchio, D Huang, YY Gupta, A Hamblin, MR AF Yin, Rui Dai, Tianhong Avci, Pinar Serafim Jorge, Ana Elisa de Melo, Wanessa C. M. A. Vecchio, Daniela Huang, Ying-Ying Gupta, Asheesh Hamblin, Michael R. TI Light based anti-infectives: ultraviolet C irradiation, photodynamic therapy, blue light, and beyond SO CURRENT OPINION IN PHARMACOLOGY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; DELTA-AMINOLEVULINIC-ACID; GRAM-NEGATIVE BACTERIA; DERMATOPHYTE TRICHOPHYTON-RUBRUM; EXPERIMENTAL PERIODONTAL-DISEASE; ANTIMICROBIAL CHEMOTHERAPY PACT; HELICOBACTER-PYLORI INFECTION; CRUZI TRYPOMASTIGOTE FORMS; LOW ENVIRONMENTAL-IMPACT; MYCOBACTERIUM-BOVIS BCG AB Owing to the worldwide increase in antibiotic resistance, researchers are investigating alternative anti-infective strategies to which it is supposed microorganisms will be unable to develop resistance. Prominent among these strategies, is a group of approaches which rely on light to deliver the killing blow. As is well known, ultraviolet light, particularly UVC (200-280 nm), is germicidal, but it has not been much developed as an anti-infective approach until recently, when it was realized that the possible adverse effects to host tissue were relatively minor compared to its high activity in killing pathogens. Photodynamic therapy is the combination of non-toxic photosensitizing dyes with harmless visible light that together produce abundant destructive reactive oxygen species (ROS). Certain cationic dyes or photosensitizers have good specificity for binding to microbial cells while sparing host mammalian cells and can be used for treating many localized infections, both superficial and even deep-seated by using fiber optic delivered light. Many microbial cells are highly sensitive to killing by blue light (400-470 nm) due to accumulation of naturally occurring photosensitizers such as porphyrins and flavins. Near infrared light has also been shown to have antimicrobial effects against certain species. Clinical applications of these technologies include skin, dental, wound, stomach, nasal, toenail and other infections which are amenable to effective light delivery. C1 [Yin, Rui; Dai, Tianhong; Avci, Pinar; Serafim Jorge, Ana Elisa; de Melo, Wanessa C. M. A.; Vecchio, Daniela; Huang, Ying-Ying; Gupta, Asheesh; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Yin, Rui; Dai, Tianhong; Avci, Pinar; Vecchio, Daniela; Huang, Ying-Ying; Gupta, Asheesh; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Yin, Rui] Third Mil Med Univ, Southwest Hosp, Dept Dermatol, Chongqing, Peoples R China. [Avci, Pinar] Semmelweis Univ, Sch Med, Dept Dermatol Dermatooncol & Venerol, H-1085 Budapest, Hungary. [Serafim Jorge, Ana Elisa] Univ Sao Paulo, EESC FMRP IQSC, Programa Posgrad Interunidades Bioengn, Sao Carlos, SP, Brazil. [Serafim Jorge, Ana Elisa] Univ Sao Paulo, Inst Fis Sao Carlos, Ctr Pesquisa Opt & Foton, Sao Carlos, SP, Brazil. [de Melo, Wanessa C. M. A.] Univ Sao Paulo, Sao Carlos, SP, Brazil. [Huang, Ying-Ying] Guangxi Med Univ, Dept Pathol, Nanning, Guangxi, Peoples R China. [Gupta, Asheesh] Def Inst Physiol & Allied Sci, Delhi, India. [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 RI Sao Carlos Institute of Physics, IFSC/USP/M-2664-2016; OI Hamblin, Michael/0000-0001-6431-4605 FU US NIH [R01AI050875]; National Natural Science Foundation of China [81172495]; Airlift Research Foundation Extremity Trauma Research Grant [109421]; CAPES (Coordination for the Improvement of Higher Level Personnel) from Brazil; Department of Science and Technology, Government of India [2010-11] FX Research in the Hamblin laboratory is supported by US NIH grant R01AI050875. Rui Yin was supported in part by National Natural Science Foundation of China (No. 81172495) in this work. Tianhong Dai was supported by an Airlift Research Foundation Extremity Trauma Research Grant (No. 109421). Ana Jorge and Wanessa de Melo were supported by CAPES (Coordination for the Improvement of Higher Level Personnel) from Brazil. Asheesh Gupta was supported by BOYSCAST Fellowship 2010-11, Department of Science and Technology, Government of India. NR 283 TC 34 Z9 35 U1 3 U2 57 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 EI 1471-4973 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD OCT PY 2013 VL 13 IS 5 BP 731 EP 762 DI 10.1016/j.coph.2013.08.009 PG 32 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 241BD UT WOS:000326140500008 PM 24060701 ER PT J AU Metra, M Ponikowski, P Cotter, G Davison, BA Felker, GM Filippatos, G Greenberg, BH Hua, TA Severin, T Unemori, E Voors, AA Teerlink, JR AF Metra, Marco Ponikowski, Piotr Cotter, Gad Davison, Beth A. Felker, G. Michael Filippatos, Gerasimos Greenberg, Barry H. Hua, Tsushung A. Severin, Thomas Unemori, Elaine Voors, Adriaan A. Teerlink, John R. TI Effects of serelaxin in subgroups of patients with acute heart failure: results from RELAX-AHF SO EUROPEAN HEART JOURNAL LA English DT Article DE Acute heart failure; Serelaxin; Mortality; Subgroups ID NATRIURETIC PEPTIDE; CLINICAL-TRIALS; OUTCOMES; HOSPITALIZATION; ANTAGONIST; PROGRAM; STATE AB Aim Patients hospitalized for acute heart failure (AHF) differ with respect of many clinical characteristics which may influence their prognosis and response to treatment. We have assessed possible differences in the effects of serelaxin on dyspnoea relief, 60 Day outcomes and 180 Day mortality across patient subgroups in the RELAX-AHF trial. Methods and results Subgroups were based on pre-specified covariates (age, sex, race, geographic region, estimated glomerular filtration rate, time from presentation to randomization, baseline systolic blood pressure, history of diabetes, atrial fibrillation, ischaemic heart disease, cardiac devices, i.v. nitrates at randomization). Other covariates which may modify the efficacy of AHF treatment were also analysed. Subgroup analyses did not show any difference in the effects of serelaxin vs. placebo on dyspnoea relief or on the incidence of cardiovascular death or rehospitalizations for heart failure or renal failure at 60 days. Nominally significant interactions between some patient subgroups and the effects of serelaxin on 180 days cardiovascular and all-cause mortality were noted but should be interpreted cautiously due to the number of comparisons and the low incidence of deaths in the subgroups at lower risk. Conclusion The effects of serelaxin vs. placebo appeared to be similar across subgroups of patients in RELAX-AHF. C1 [Metra, Marco] Univ Brescia, Dept Med & Surg Specialties, Brescia, Italy. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Cotter, Gad; Davison, Beth A.] Momentum Res Inc, Durham, NC USA. [Felker, G. Michael] Duke Univ, Sch Med, Duke Heart Ctr, Durham, NC USA. [Filippatos, Gerasimos] Athens Univ Hosp, Athens, Greece. [Greenberg, Barry H.] Univ Calif San Diego, San Diego, CA 92103 USA. [Hua, Tsushung A.] Novartis Pharmaceut, E Hanover, NJ USA. [Severin, Thomas] Novartis Pharma AG, Basel, Switzerland. [Unemori, Elaine] Corthera Inc, San Carlos, CA USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Metra, M (reprint author), Spedali Civil Brescia, Piazza Spedali Civili 1, I-25123 Brescia, Italy. EM metramarco@libero.it RI Lainscak, Mitja/F-3237-2015; Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Metra, Marco/0000-0001-6691-8568; Davison, Beth/0000-0003-2374-6449 FU Corthera, Inc.; Novartis Pharma AG, Basel, Switzerland FX The RELAX-AHF trial was supported by Corthera, Inc., a member of the Novartis group of companies. Graham Allcock of CircleScience provided editorial assistance, which was funded by Novartis Pharma AG, Basel, Switzerland. NR 29 TC 27 Z9 29 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD OCT PY 2013 VL 34 IS 40 BP 3128 EP 3136 DI 10.1093/eurheartj/eht371 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243BX UT WOS:000326292600012 PM 23999454 ER PT J AU Drubach, LA Palmer, EL Stamoulis, C Jenkins, KJ Marshall, AC Cao, X Lee, EY AF Drubach, L. A. Palmer, E. L. Stamoulis, C. Jenkins, K. J. Marshall, A. C. Cao, X. Lee, E. Y. TI Correlation of the Findings of Quantitative 99mTc MAA Lung Scintigraphy and Cardiac Catheterization in pediatric patients with Pulmonary Vein Stenosis SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract CT Annual Congress of the European-Association-of-Nuclear-Medicine (EANM) CY OCT 19-23, 2013 CL Lyon, FRANCE SP European Assoc Nucl Med C1 [Drubach, L. A.; Stamoulis, C.; Jenkins, K. J.; Marshall, A. C.; Cao, X.; Lee, E. Y.] Boston Childrens Hosp, Boston, MA USA. [Palmer, E. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 EI 1619-7089 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD OCT PY 2013 VL 40 SU 2 BP S165 EP S165 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 237FG UT WOS:000325853400217 ER PT J AU McQuaid, SJ Kijewski, MF Moore, SC Park, M Sitek, A Gualtieri, E Perkins, A Daube-Witherspoon, M Karp, JS AF McQuaid, S. J. Kijewski, M. F. Moore, S. C. Park, M. Sitek, A. Gualtieri, E. Perkins, A. Daube-Witherspoon, M. Karp, J. S. TI Estimating Cardiac Kinetic Parameters Using Dynamic Time-of-Flight PET SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract CT Annual Congress of the European-Association-of-Nuclear-Medicine (EANM) CY OCT 19-23, 2013 CL Lyon, FRANCE SP European Assoc Nucl Med C1 [McQuaid, S. J.] Royal Surrey Cty Hosp, Guildford, Surrey, England. [Kijewski, M. F.; Moore, S. C.; Park, M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kijewski, M. F.; Moore, S. C.; Park, M.; Sitek, A.] Harvard Univ, Sch Med, Boston, MA USA. 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TI Visualization of brown adipose tissue recruitment in human adults by means of dynamic and static [F-18]FDG PET/CT-imaging SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract CT Annual Congress of the European-Association-of-Nuclear-Medicine (EANM) CY OCT 19-23, 2013 CL Lyon, FRANCE SP European Assoc Nucl Med C1 [van der Lans, A.; Lichtenbelt, W. van Marken; Hoeks, J.; Vosselmans, M.; Hansen, J.; Jorgensen, J.; Schrauwen, P.] Univ Maastricht, Maastricht, Netherlands. [Vijgen, G.; Visser, M.; Brans, B.] Univ Maastricht, Med Ctr, Maastricht, Netherlands. [Wu, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wu, J.] Harvard Univ, Sch Med, Boston, MA USA. [Mottaghy, F.] Univ Hosp RWTH Aachen, Aachen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 EI 1619-7089 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. 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