FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kim, BM You, MH Chen, CH Suh, J Tanzi, RE Lee, TH AF Kim, Byeong Mo You, Mi-Hyeon Chen, Chun-Hau Suh, Jaehong Tanzi, Rudolph E. Lee, Tae Ho TI Inhibition of death-associated protein kinase 1 attenuates the phosphorylation and amyloidogenic processing of amyloid precursor protein SO HUMAN MOLECULAR GENETICS LA English DT Article ID A-BETA PEPTIDES; ALZHEIMERS-DISEASE; DAP-KINASE; NEURONAL DIFFERENTIATION; TRANSGENIC MICE; ISOMERASE PIN1; CELL-DEATH; SECRETASE CLEAVAGE; CYTOPLASMIC DOMAIN; OXIDATIVE STRESS AB Extracellular deposition of amyloid-beta (A beta) peptide, a metabolite of sequential cleavage of amyloid precursor protein (APP), is a critical step in the pathogenesis of Alzheimer's disease (AD). While death-associated protein kinase 1 (DAPK1) is highly expressed in AD brains and its genetic variants are linked to AD risk, little is known about the impact of DAPK1 on APP metabolism and A beta generation. In this study, we demonstrated a novel effect of DAPK1 in the regulation of APP processing using cell culture and mouse models. DAPK1, but not its kinase deficient mutant (K42A), significantly increased human A beta secretion in neuronal cell culture models. Moreover, knockdown of DAPK1 expression or inhibition of DAPK1 catalytic activity significantly decreased A beta secretion. Furthermore, DAPK1, but not K42A, triggered Thr668 phosphorylation of APP, which may initiate and facilitate amyloidogenic APP processing leading to the generation of A beta. In Tg2576 APPswe-overexpressing mice, knockout of DAPK1 shifted APP processing toward non-amyloidogenic pathway and decreased A beta generation. Finally, in AD brains, elevated DAPK1 levels showed co-relation with the increase of APP phosphorylation. Combined together, these results suggest that DAPK1 promotes the phosphorylation and amyloidogenic processing of APP, and that may serve a potential therapeutic target for AD. C1 [Kim, Byeong Mo; You, Mi-Hyeon; Lee, Tae Ho] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, Div Gerontol, Boston, MA 02215 USA. [Kim, Byeong Mo] Yonsei Univ, Coll Med, Severance Integrat Res Inst Cerebral & Cardiovasc, Seoul 120752, South Korea. [Chen, Chun-Hau] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. [Suh, Jaehong; Tanzi, Rudolph E.] Harvard Med Sch, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit,Dept Neurol, Boston, MA 02129 USA. RP Lee, TH (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. EM tlee3@bidmc.harvard.edu FU Korea Healthcare technology R&D Project, Ministry for Health & Welfare Affairs, Republic of Korea [HI08C2149]; Yonsei University College of Medicine [2014-32-0048]; NIH [R00AG033104]; Alzheimer's Association [NIRG-12-258863]; American Federation for Aging Research; Massachusetts Alzheimer's Disease Research Center [P50AG005134] FX This work was supported by a grant of the Korea Healthcare technology R&D Project, Ministry for Health & Welfare Affairs, Republic of Korea (No. HI08C2149) and by a faculty research grant of Yonsei University College of Medicine for 2014 (No. 2014-32-0048) to B.M.K. and NIH grant (R00AG033104), the Alzheimer's Association (NIRG-12-258863), the American Federation for Aging Research, and the Massachusetts Alzheimer's Disease Research Center (P50AG005134) to T.H.L. NR 78 TC 0 Z9 0 U1 3 U2 3 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 JUN 15 PY 2016 VL 25 IS 12 BP 2498 EP 2513 DI 10.1093/hmg/ddw114 PG 16 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA EJ2TA UT WOS:000393062900010 PM 27094130 ER PT J AU Garanto, A Chung, DC Duijkers, L Corral-Serrano, JC Messchaert, M Xiao, R Bennett, J Vandenberghe, LH Collin, RWJ AF Garanto, Alejandro Chung, Daniel C. Duijkers, Lonneke Corral-Serrano, Julio C. Messchaert, Muriel Xiao, Ru Bennett, Jean Vandenberghe, Luk H. Collin, Rob W. J. TI In vitro and in vivo rescue of aberrant splicing in CEP290-associated LCA by antisense oligonucleotide delivery SO HUMAN MOLECULAR GENETICS LA English DT Article ID LEBER CONGENITAL AMAUROSIS; RETINAL GENE-THERAPY; ADENOASSOCIATED VIRUS; RPE65 MUTATIONS; AAV VECTORS; CEP290; MODEL; BLINDNESS; MEMBRANE; PHOTORECEPTORS AB Leber congenital amaurosis (LCA) is a severe disorder resulting in visual impairment usually starting in the first year of life. The most frequent genetic cause of LCA is an intronic mutation in CEP290 (c.2991+1655A>G) that creates a cryptic splice donor site resulting in the insertion of a pseudoexon (exon X) into CEP290 mRNA. Previously, we showed that naked antisense oligonucleotides (AONs) effectively restored normal CEP290 splicing in patient-derived lymphoblastoid cells. We here explore the therapeutic potential of naked and adeno-associated virus (AAV)-packaged AONs in vitro and in vivo. In both cases, AON delivery fully restored CEP290 pre-mRNA splicing, significantly increased CEP290 protein levels and rescued a ciliary phenotype present in patient-derived fibroblast cells. Moreover, administration of naked and AAV-packaged AONs to the retina of a humanized mutant Cep290 mouse model, carrying the intronic mutation, showed a statistically significant reduction of exon X-containing Cep290 transcripts, without compromising the retinal structure. Together, our data highlight the tremendous therapeutic prospective of AONs for the treatment of not only CEP290-associated LCA but potentially many other subtypes of retinal dystrophy caused by splicing mutations. C1 [Garanto, Alejandro; Duijkers, Lonneke; Corral-Serrano, Julio C.; Messchaert, Muriel; Collin, Rob W. J.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 GA Nijmegen, Netherlands. [Garanto, Alejandro; Messchaert, Muriel; Collin, Rob W. J.] Radboud Univ Nijmegen, Med Ctr, Donders Ctr Neurosci, NL-6525 GA Nijmegen, Netherlands. [Chung, Daniel C.; Bennett, Jean] Univ Penn, Sch Med, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA. [Chung, Daniel C.; Bennett, Jean] Univ Penn, Sch Med, Scheie Eye Inst, Ctr Adv Retinal & Ophthalm Therapeut, Philadelphia, PA 19104 USA. [Corral-Serrano, Julio C.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, NL-6525 GA Nijmegen, Netherlands. [Xiao, Ru; Vandenberghe, Luk H.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Grousbeck Gene Therapy Ctr,Dept Ophthalmol, Boston, MA 02114 USA. RP Collin, RWJ (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Human Genet 855, Geert Grootepl Zuid 10, NL-6525 GA Nijmegen, Netherlands. EM rob.collin@radboudumc.nl FU Netherlands Organisation for Scientific Research (NWO) [VENI 916.10.096]; Foundation Fighting Blindness (FFB) USA [TA-GT-0912-0582-RAD]; FP7-PEOPLE-ITN programme EyeTN, Brussels, Belgium [317472]; JANIVO stichting; Stichting August F. Deutman Researchfonds Oogheelkunde; Rotterdamse Vereniging Blindenbelangen; Algemene Nederlandse Vereniging ter Voorkoming van Blindheid; Gelderse Blindenstichting; Stichting Winckel-Sweep; Stichting Nederlands Oogheelkundig Onderzoek; FFB [C-GT-09130627-UPA02]; NIH [DP1-OD008267]; Curing Kids Fund, FFB [TA-GT-0611-0571]; Grousbeck Family Foundation FX This work is financially supported by the Netherlands Organisation for Scientific Research (NWO) (VENI 916.10.096), the Foundation Fighting Blindness (FFB) USA (TA-GT-0912-0582-RAD), FP7-PEOPLE-2012-ITN programme EyeTN, Brussels, Belgium (agreement no.: 317472), the JANIVO stichting, the Stichting August F. Deutman Researchfonds Oogheelkunde, the Rotterdamse Vereniging Blindenbelangen, the Algemene Nederlandse Vereniging ter Voorkoming van Blindheid, the Gelderse Blindenstichting, the Stichting Winckel-Sweep and the Stichting Nederlands Oogheelkundig Onderzoek (all to R.W.J.C.), FFB (C-GT-09130627-UPA02) to J.B., the NIH (DP1-OD008267) to J.B. and L.H.V., the Curing Kids Fund, FFB (TA-GT-0611-0571) and the Grousbeck Family Foundation (all to L.H.V.). NR 53 TC 2 Z9 2 U1 0 U2 0 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 JUN 15 PY 2016 VL 25 IS 12 BP 2552 EP 2563 DI 10.1093/hmg/ddw118 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA EJ2TA UT WOS:000393062900014 PM 27106101 ER PT J AU Ora, H Wada, M Salat, D Kansaku, K AF Ora, Hiroki Wada, Makoto Salat, David Kansaku, Kenji TI Arm crossing updates brain functional connectivity of the left posterior parietal cortex SO SCIENTIFIC REPORTS LA English DT Article ID RESTING HUMAN BRAIN; EVENT-RELATED FMRI; MULTISENSORY REPRESENTATION; COMPONENT ANALYSIS; PREMOTOR CORTEX; DEFAULT NETWORK; SYSTEM; ORGANIZATION; INTEGRATION; MOVEMENTS AB The unusual configuration of body parts can cause illusions. For example, when tactile stimuli are delivered to crossed arms a reversal of subjective temporal ordering occurs. Our group has previously demonstrated that arm crossing without sensory stimuli causes activity changes in the left posterior parietal cortex (PPC) and an assessment of tactile temporal order judgments (TOJs) revealed a positive association between activity in this area, especially the left intraparietal sulcus (IPS), and the degree of the crossed-hand illusion. Thus, the present study investigated how the IPS actively relates to other cortical areas under arms-crossed and -uncrossed conditions by analyzing the functional connectivity of the IPS. Regions showing connectivity with the IPS overlapped with regions within the default mode network (DMN) but the IPS also showed connectivity with other brain areas, including the frontoparietal control network (FPCN). The right middle/inferior frontal gyrus (MFG/IFG), which is included in the FPCN, showed greater connectivity in the arms-crossed condition than in the arms-uncrossed condition. These findings suggest that there is state-dependent connectivity during arm crossing, and that the left IPS may play an important role during the spatio-temporal updating of arm positions. C1 [Ora, Hiroki; Wada, Makoto; Kansaku, Kenji] Natl Rehabil Ctr Persons Disabil, Res Inst, Dept Rehabil Brain Funct, Syst Neurosci Sect, Tokorozawa, Saitama 3598555, Japan. [Ora, Hiroki; Kansaku, Kenji] Univ Electrocommun, Brain Sci Inspired Life Support Res Ctr, Chofu, Tokyo 1820021, Japan. [Ora, Hiroki] Tokyo Inst Technol, Dept Computat Intelligence & Syst Sci, Yokohama, Kanagawa 2268503, Japan. [Salat, David] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Kansaku, K (reprint author), Natl Rehabil Ctr Persons Disabil, Res Inst, Dept Rehabil Brain Funct, Syst Neurosci Sect, Tokorozawa, Saitama 3598555, Japan.; Kansaku, K (reprint author), Univ Electrocommun, Brain Sci Inspired Life Support Res Ctr, Chofu, Tokyo 1820021, Japan. EM kansaku-kenji@rehab.go.jp RI Ora, Hiroki/B-2407-2008 OI Ora, Hiroki/0000-0001-8393-8982 FU MEXT/JSPS grant [21650062, 23300151, 15H03126, 15H05880, 16K13113]; MHLW/AMED grant (BMI); MEXT/AMED-SRPBS grant FX This study was partly supported by MEXT/JSPS grants (#21650062, #23300151, 15H03126, 15H05880 and 16K13113), a MHLW/AMED grant (BMI), and a MEXT/AMED-SRPBS grant. We thank Dr. K. Takano for his help, and Drs. Y. Nakajima and F. Eto for their encouragement throughout the study. NR 56 TC 0 Z9 0 U1 0 U2 0 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 JUN 15 PY 2016 VL 6 AR 28105 DI 10.1038/srep28105 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DX7ZM UT WOS:000384607900001 PM 27302746 ER PT J AU Wang, C Shelton, K Ortiz, VE AF Wang, Connie Shelton, Kenneth Ortiz, Vilma E. TI How Rescue Echocardiography Changed the Intraoperative Management of an Obese Patient with Refractory Hypotension? SO A & A CASE REPORTS LA English DT Article ID PERIOPERATIVE TRANSESOPHAGEAL ECHOCARDIOGRAPHY; INSUFFLATION; GUIDELINES; SURGERY AB The value of perioperative echocardiography as a rescue tool to complement the clinical assessment of patients who develop hemodynamic instability during noncardiac surgery is becoming increasingly recognized. Several studies have demonstrated the utility of echocardiography in establishing a diagnosis during clinical emergencies. We present the case of an obese patient with refractory hypotension during laparoscopic gynecologic surgery in which rescue transesophageal echocardiography was pivotal in elucidating a diagnosis and changing the course of management. C1 [Wang, Connie; Shelton, Kenneth; Ortiz, Vilma E.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. RP Wang, C (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM cwang12186@gmail.com NR 11 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2325-7237 J9 A A CASE REP JI A A Case Rep. PD JUN 15 PY 2016 VL 6 IS 12 BP 391 EP 393 DI 10.1213/XAA.0000000000000358 PG 3 WC Anesthesiology SC Anesthesiology GA DS1ZJ UT WOS:000380502100007 PM 27301054 ER PT J AU Deaton, AM Gomez-Rodriguez, M Mieczkowski, J Tolstorukov, MY Kundu, S Sadreyev, RI Jansen, LET Kingston, RE AF Deaton, Aimee M. Gomez-Rodriguez, Mariluz Mieczkowski, Jakub Tolstorukov, Michael Y. Kundu, Sharmistha Sadreyev, Ruslan I. Jansen, Lars E. T. Kingston, Robert E. TI Enhancer regions show high histone H3.3 turnover that changes during differentiation SO ELIFE LA English DT Article ID EMBRYONIC STEM-CELLS; CENP-A NUCLEOSOMES; VARIANT H3.3; TRANSCRIPTION FACTORS; ACTIVE TRANSCRIPTION; REGULATORY REGIONS; RNA-SEQ; IN-VIVO; CHROMATIN; DNA AB The organization of DNA into chromatin is dynamic; nucleosomes are frequently displaced to facilitate the ability of regulatory proteins to access specific DNA elements. To gain insight into nucleosome dynamics, and to follow how dynamics change during differentiation, we used a technique called time-ChIP to quantitatively assess histone H3.3 turnover genome-wide during differentiation of mouse ESCs. We found that, without prior assumptions, high turnover could be used to identify regions involved in gene regulation. High turnover was seen at enhancers, as observed previously, with particularly high turnover at super-enhancers. In contrast, regions associated with the repressive Polycomb-Group showed low turnover in ESCs. Turnover correlated with DNA accessibility. Upon differentiation, numerous changes in H3.3 turnover rates were observed, the majority of which occurred at enhancers. Thus, time-ChIP measurement of histone turnover shows that active enhancers are unusually dynamic in ESCs and changes in highly dynamic nucleosomes predominate at enhancers during differentiation. C1 [Deaton, Aimee M.; Mieczkowski, Jakub; Tolstorukov, Michael Y.; Kundu, Sharmistha; Sadreyev, Ruslan I.; Kingston, Robert E.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Deaton, Aimee M.; Mieczkowski, Jakub; Kundu, Sharmistha; Kingston, Robert E.] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA. [Gomez-Rodriguez, Mariluz; Jansen, Lars E. T.] Inst Gulbenkian Ciencias, Lab Epigenet Mech, Oeiras, Portugal. [Tolstorukov, Michael Y.] Harvard Med Sch, Dept Med, Boston, MA USA. [Sadreyev, Ruslan I.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sadreyev, Ruslan I.] Harvard Med Sch, Boston, MA USA. [Deaton, Aimee M.] Amgen Inc, Cambridge, MA USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.; Kingston, RE (reprint author), Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.; Jansen, LET (reprint author), Inst Gulbenkian Ciencias, Lab Epigenet Mech, Oeiras, Portugal. EM ljansen@igc.gulbenkian.pt; kingston@molbio.mgh.harvard.edu OI Jansen, Lars/0000-0002-2158-0345; Mieczkowski, Jakub/0000-0002-2091-012X FU National Institutes of Health [NIH R01 GM48405]; Fundacao para a Ciencia e a Tecnologia [BIA-PRO/100537/2008, SFRH/BD/33567/2008]; European Molecular Biology Organization [1818]; European Research Council [ERC-2013-CoG-615638] FX National Institutes of Health Grant reference number Author NIH R01 GM48405 Robert E Kingston; Fundacao para a Ciencia e a Tecnologia BIA-PRO/100537/2008 Lars ET Jansen; Fundacao para a Ciencia e a Tecnologia SFRH/BD/33567/2008 Mariluz Gomez-Rodriguez; European Molecular Biology Organization installation grant 1818 Lars ET Jansen; European Research Council ERC-2013-CoG-615638 Lars ET Jansen; The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. NR 46 TC 1 Z9 1 U1 2 U2 5 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD JUN 15 PY 2016 VL 5 AR e15316 DI 10.7554/eLife.15316 PG 24 WC Biology SC Life Sciences & Biomedicine - Other Topics GA DS6RO UT WOS:000380910200001 ER PT J AU Martin, J Tilling, K Hubbard, L Stergiakouli, E Thapar, A Smith, GD O'Donovan, MC Zammit, S AF Martin, Joanna Tilling, Kate Hubbard, Leon Stergiakouli, Evie Thapar, Anita Smith, George Davey O'Donovan, Michael C. Zammit, Stanley TI Association of Genetic Risk for Schizophrenia With Nonparticipation Over Time in a Population-Based Cohort Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Avon Longitudinal Study of Parents and Children; attrition bias; cohort studies; genetic risk; longitudinal studies; schizophrenia; study nonparticipation ID PSYCHIATRIC-DISORDERS; ADULT SCHIZOPHRENIA; SELECTION BIAS; ATTRITION; INSIGHTS; BEHAVIOR; LOCI AB Progress has recently been made in understanding the genetic basis of schizophrenia and other psychiatric disorders. Longitudinal studies are complicated by participant dropout, which could be related to the presence of psychiatric problems and associated genetic risk. We tested whether common genetic variants implicated in schizophrenia were associated with study nonparticipation among 7,867 children and 7,850 mothers from the Avon Longitudinal Study of Parents and Children (ALSPAC; 1991-2007), a longitudinal population cohort study. Higher polygenic risk scores for schizophrenia were consistently associated with noncompletion of questionnaires by study mothers and children and nonattendance at data collection throughout childhood and adolescence (ages 1-15 years). These associations persisted after adjustment for other potential correlates of nonparticipation. Results suggest that persons at higher genetic risk for schizophrenia are likely to be underrepresented in cohort studies, which will underestimate risk of this and related psychiatric, cognitive, and behavioral phenotypes in the population. Statistical power to detect associations with these phenotypes will be reduced, while analyses of schizophrenia-related phenotypes as outcomes may be biased by the nonrandom missingness of these phenotypes, even if multiple imputation is used. Similarly, in complete-case analyses, collider bias may affect associations between genetic risk and other factors associated with missingness. C1 [Martin, Joanna; Hubbard, Leon; Thapar, Anita; O'Donovan, Michael C.; Zammit, Stanley] Cardiff Univ, Sch Med, Ctr Neuropsychiatr Genet & Genom, MRC,Inst Psychol Med & Clin Neurosci, Hadyn Ellis Bldg,Maindy Rd, Cardiff CF24 4HQ, S Glam, Wales. [Martin, Joanna] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Martin, Joanna] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Tilling, Kate; Stergiakouli, Evie; Smith, George Davey; Zammit, Stanley] Univ Bristol, MRC, Integrat Epidemiol Unit, Bristol, Avon, England. RP Martin, J (reprint author), Cardiff Univ, Sch Med, Ctr Neuropsychiatr Genet & Genom, MRC,Inst Psychol Med & Clin Neurosci, Hadyn Ellis Bldg,Maindy Rd, Cardiff CF24 4HQ, S Glam, Wales. EM martinjm1@cardiff.ac.uk RI Davey Smith, George/A-7407-2013; OI Davey Smith, George/0000-0002-1407-8314; Thapar, Anita/0000-0002-3689-737X; Stergiakouli, Evangelia/0000-0003-3586-0927; Tilling, Kate/0000-0002-1010-8926 FU Wellcome Trust [092731, 106047]; Medical Research Council (MRC) [MR/M006727/1] FX This work was supported by the Wellcome Trust (grants 092731 and 106047) and the Medical Research Council (MRC) (including MRC grant MR/M006727/1). The University of Bristol also provides core support for the Avon Longitudinal Study of Parents and Children (ALSPAC). NR 24 TC 5 Z9 5 U1 5 U2 10 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 JUN 15 PY 2016 VL 183 IS 12 BP 1149 EP 1158 DI 10.1093/aje/kww009 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DR2IQ UT WOS:000379728600011 PM 27188935 ER PT J AU Wagner, J Paulson, JN Wang, X Bhattacharjee, B Bravo, HC AF Wagner, Justin Paulson, Joseph N. Wang, Xiao Bhattacharjee, Bobby Bravo, Hector Corrada TI Privacy-preserving microbiome analysis using secure computation SO BIOINFORMATICS LA English DT Article AB Motivation: Developing targeted therapeutics and identifying biomarkers relies on large amounts of research participant data. Beyond human DNA, scientists now investigate the DNA of micro-organisms inhabiting the human body. Recent work shows that an individual's collection of microbial DNA consistently identifies that person and could be used to link a real-world identity to a sensitive attribute in a research dataset. Unfortunately, the current suite of DNA-specific privacy-preserving analysis tools does not meet the requirements for microbiome sequencing studies. Results: To address privacy concerns around microbiome sequencing, we implement metagenomic analyses using secure computation. Our implementation allows comparative analysis over combined data without revealing the feature counts for any individual sample. We focus on three analyses and perform an evaluation on datasets currently used by the microbiome research community. We use our implementation to simulate sharing data between four policy-domains. Additionally, we describe an application of our implementation for patients to combine data that allows drug developers to query against and compensate patients for the analysis. C1 [Wagner, Justin; Paulson, Joseph N.; Bravo, Hector Corrada] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA. [Wang, Xiao; Bhattacharjee, Bobby] Univ Maryland, Dept Comp Sci, Maryland Cybersecur Ctr, College Pk, MD 20742 USA. [Paulson, Joseph N.] Harvard TH Chan Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA USA. [Paulson, Joseph N.] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Bravo, HC (reprint author), Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA. EM hcorrada@umiacs.umd.edu FU National Institutes of Health [R01HG005220, R01GM114267]; US National Science Foundation Graduate Research Fellowship [DGE0750616]; US National Science Foundation [1111599, 1314857, 0964541] FX This work was partially supported by the National Institutes of Health [R01HG005220 and R01GM114267 to H.C.B. and J.W.]; the US National Science Foundation Graduate Research Fellowship [DGE0750616 to J.N.P.]; and the US National Science Foundation [1111599 to X.W., 1314857 to X.W., 0964541 to B.B.]. NR 26 TC 0 Z9 0 U1 3 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 EI 1460-2059 J9 BIOINFORMATICS JI Bioinformatics PD JUN 15 PY 2016 VL 32 IS 12 BP 1873 EP 1879 DI 10.1093/bioinformatics/btw073 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA DR2KV UT WOS:000379734300058 PM 26873931 ER PT J AU Tokhtaeva, E Sun, HY Deiss-Yehiely, N Wen, Y Soni, PN Gabrielli, NM Marcus, EA Ridge, KM Sachs, G Vazquez-Levin, M Sznajder, JI Vagin, O Dada, LA AF Tokhtaeva, Elmira Sun, Haying Deiss-Yehiely, Nimrod Wen, Yi Soni, Pritin N. Gabrielli, Nieves M. Marcus, Elizabeth A. Ridge, Karen M. Sachs, George Vazquez-Levin, Monica Sznajder, Jacob I. Vagin, Olga Dada, Laura A. TI The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell-cell trans-dimerization of Na, K-ATPase beta(1) subunits SO JOURNAL OF CELL SCIENCE LA English DT Article DE Na; K-ATPase; Epithelium; Epithelial cell adhesion molecule; Cell-cell interaction; Cell adhesion; O-glycosylation; FXYD5 ID ALVEOLAR EPITHELIAL-CELLS; PULMONARY-EDEMA CLEARANCE; LUNG LIQUID CLEARANCE; E-CADHERIN EXPRESSION; BREAST-CANCER CELLS; DYSADHERIN EXPRESSION; PLASMA-MEMBRANE; TIGHT JUNCTIONS; DOWN-REGULATION; NA+/K+-ATPASE AB FXYD5 (also known as dysadherin), a regulatory subunit of the Na, K-ATPase, impairs intercellular adhesion by a poorly understood mechanism. Here, we determined whether FXYD5 disrupts the trans-dimerization of Na, K-ATPase molecules located in neighboring cells. Mutagenesis of the Na, K-ATPase beta(1) subunit identified four conserved residues, including Y199, that are crucial for the intercellular Na, K-ATPase trans-dimerization and adhesion. Modulation of expression of FXYD5 or of the beta(1) subunit with intact or mutated beta(1)-beta(1) binding sites demonstrated that the anti-adhesive effect of FXYD5 depends on the presence of Y199 in the beta(1) subunit. Immunodetection of the plasma membrane FXYD5 was prevented by the presence of O-glycans. Partial FXYD5 deglycosylation enabled antibody binding and showed that the protein level and the degree of O-glycosylation were greater in cancer than in normal cells. FXYD5- induced impairment of adhesion was abolished by both genetic and pharmacological inhibition of FXYD5 O-glycosylation. Therefore, the extracellular O-glycosylated domain of FXYD5 impairs adhesion by interfering with intercellular beta(1)-beta(1) interactions, suggesting that the ratio between FXYD5 and alpha(1)-beta(1) heterodimer determines whether the Na, K-ATPase acts as a positive or negative regulator of intercellular adhesion. C1 [Tokhtaeva, Elmira; Wen, Yi; Sachs, George; Vagin, Olga] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. [Tokhtaeva, Elmira; Wen, Yi; Marcus, Elizabeth A.; Sachs, George; Vagin, Olga] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Sun, Haying; Deiss-Yehiely, Nimrod; Soni, Pritin N.; Gabrielli, Nieves M.; Ridge, Karen M.; Sznajder, Jacob I.; Dada, Laura A.] Northwestern Univ, Feinberg Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60611 USA. [Gabrielli, Nieves M.; Vazquez-Levin, Monica] Consejo Nacl Invest Cient & Tecn, Inst Biol & Med Expt, FIBYME, C1418ADN, Buenos Aires, DF, Argentina. [Marcus, Elizabeth A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. RP Dada, LA (reprint author), Northwestern Univ, Feinberg Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60611 USA. EM lauradada@northwestern.edu FU National Institutes of Health [R37-HL48129, HL071643, HL113350, USVA 2I01BX001006, DK105156-01, PICT_SU1072, K08DK100661]; UCLA Children's Discovery and Innovation Institute FX This work was supported, in part, by the National Institutes of Health [grant numbers R37-HL48129 to J.I.S., HL071643 to J.I.S., K.M.R. and L.A.D., HL113350 to L.A.D. and O.V., USVA 2I01BX001006 to G.S., DK105156-01 to G.S., PICT_SU1072 to M.V.-L., K08DK100661 to E.A.M.]; and the UCLA Children's Discovery and Innovation Institute (to E.A.M.). Deposited in PMC for release after 12 months. NR 65 TC 0 Z9 0 U1 4 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 EI 1477-9137 J9 J CELL SCI JI J. Cell Sci. PD JUN 15 PY 2016 VL 129 IS 12 BP 2394 EP 2406 DI 10.1242/jcs.186148 PG 13 WC Cell Biology SC Cell Biology GA DQ8YV UT WOS:000379498500011 PM 27142834 ER PT J AU Kaji, I Akiba, Y Konno, K Watanabe, M Kimura, S Iwanaga, T Kuri, A Iwamoto, K Kuwahara, A Kaunitz, JD AF Kaji, Izumi Akiba, Yasutada Konno, Kohtarou Watanabe, Masahiko Kimura, Shunsuke Iwanaga, Toshihiko Kuri, Ayaka Iwamoto, Ken-ichi Kuwahara, Atsukazu Kaunitz, Jonathan D. TI Neural FFA3 activation inversely regulates anion secretion evoked by nicotinic ACh receptor activation in rat proximal colon SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID CHAIN FATTY-ACIDS; PROTEIN-COUPLED RECEPTOR; CHOLINE-ACETYLTRANSFERASE; ENTERIC NEURONS; GASTROINTESTINAL-TRACT; DISTAL COLON; IN-VITRO; EXPRESSION; ILEUM; TRANSPORT AB The proximal colonic mucosa is constantly exposed to high concentrations of microbially-produced short-chain fatty acids (SCFAs). Although luminal SCFAs evoke electrogenic anion secretion and smooth muscle contractility via neural and non-neural cholinergic pathways in the colon, the involvement of the SCFA receptor free fatty acid receptor (FFA)3, one of the free fatty acid receptor family members, has not been clarified. We investigated the contribution of FFA3 to cholinergic-mediated secretory responses in rat proximal colon. FFA3 was immunolocalized to enteroendocrine cells and to the enteric neural plexuses. Most FFA3-immunoreactive nerve fibres and nerve endings were cholinergic, colocalized with protein gene product (PGP)9.5, the vesicular ACh transporter, and the high-affinity choline transporter CHT1. In Ussing chambered mucosa-submucosa preparations (including the submucosal plexus) of rat proximal colon, carbachol (CCh)-induced Cl- secretion was decreased by TTX, hexamethonium, and the serosal FFA3 agonists acetate or propionate, although not by an inactive analogue 3-chloropropionate. Serosal application of a selective FFA3 agonist (N-[2-methylphenyl]-[4-furan-3-yl]-2-methyl-5-oxo-1,4,5,6,7,8-hexahydro-quinoline-3-carboxamide; MQC) dose-dependently suppressed the response to CCh but not to forskolin, with an IC50 of 13m. Pretreatment with MQC inhibited nicotine-evoked but not bethanechol-evoked secretion. The inhibitory effect of MQC was reversed by pretreatment with pertussis toxin, indicating that FFA3 acts via the G(i/o) pathway. Luminal propionate induced Cl- secretion via the cholinergic pathway, which was reduced by MQC, as well as by TTX, hexamethonium or removal of the submucosal plexus. These results suggest that the SCFA-FFA3 pathway has a novel anti-secretory function in that it inhibits cholinergic neural reflexes in the enteric nervous system. C1 [Akiba, Yasutada; Kaunitz, Jonathan D.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Kaji, Izumi; Akiba, Yasutada; Kaunitz, Jonathan D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Kaji, Izumi; Akiba, Yasutada; Kaunitz, Jonathan D.] Brentwood Biomed Res Inst, Los Angeles, CA USA. [Konno, Kohtarou; Watanabe, Masahiko; Kimura, Shunsuke; Iwanaga, Toshihiko] Hokkaido Univ, Grad Sch Med, Dept Anat, Sapporo, Hokkaido, Japan. [Kuri, Ayaka; Iwamoto, Ken-ichi; Kuwahara, Atsukazu] Univ Shizuoka, Grad Sch Integrated Pharmaceut & Nutr Sci, Shizuoka, Japan. RP Kaunitz, JD (reprint author), West Los Angeles VA Med Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu RI Kimura, Shunsuke/D-7093-2012; WATANABE, Masahiko/A-4055-2012 OI Kimura, Shunsuke/0000-0001-9408-2884; FU Department of Veterans Affairs Merit Review Award; NIH [R01 DK54221]; Comprehensive Brain Science Network (CBSN) in Japan FX This work was supported by a Department of Veterans Affairs Merit Review Award and NIH R01 DK54221. Antibody production was supported by a project of Comprehensive Brain Science Network (CBSN) in Japan. NR 53 TC 1 Z9 1 U1 4 U2 5 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 JUN 15 PY 2016 VL 594 IS 12 BP 3339 EP 3352 DI 10.1113/JP271441 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA DQ4PC UT WOS:000379184800017 PM 26854275 ER PT J AU Minami, Y Hou, JB Xing, L Jia, HB Hu, SN Vergallo, R Soeda, T Lee, H Zhang, SS Yu, B Jang, IK AF Minami, Yoshiyasu Hou, Jingbo Xing, Lei Jia, Haibo Hu, Sining Vergallo, Rocco Soeda, Tsunenari Lee, Hang Zhang, Shaosong Yu, Bo Jang, Ik-Kyung TI Serial Optical Coherence Tomography and Intravascular Ultrasound Analysis of Gender Difference in Changes of Plaque Phenotype in Response to Lipid-Lowering Therapy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID THIN-CAP FIBROATHEROMA; CORONARY-HEART-DISEASE; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; HUMAN ATHEROSCLEROSIS; VASA VASORUM; WOMEN; NEOVASCULARIZATION; MEN; METAANALYSIS AB Although the clinical benefit of statins have been demonstrated in both genders, gender differences in the response to statin therapy on plaque morphologic changes have not been reported. A total of 66 nonculprit plaques from 46 patients who had serial image acquisition at baseline, 6 months, and 12 months by both optical coherence tomography and intravascular ultrasound (IVUS) were included. Patients were treated with atorvastatin 60 mg (AT60) or 20 mg (AT20). The baseline characteristics were similar between women (n = 16) and men (n = 30) except for age (59.3 +/- 6.8 vs 52.5 +/- 10.6 years, p = 0.027) and smoking status (12.5% vs 70.0%, p <0.001). The change in fibrous cap thickness (FCT) at 12 months was significant in both groups (108.8 +/- 87.4 mu m, p <0.001, 91.3 +/- 70.1 mu m, p <0.001, respectively) without significant difference between the groups (p = 0.437). The percent change in mean lipid arc at 6 months was significantly, greater in women than that in men (- 12.8 +/- 18.8% vs - 1.56 +/- 21.8%, p = 0.040). In women, the percent change of FCT in the AT20 group was similar to that in the AT60 group (182.5 +/- 199.5% vs 192.9 +/- 149.7%, p = 0.886). However, in men, the percent change of FCT in the AT20 group was significantly smaller than that in the AT60 group (92.2 +/- 90.5% vs 225.9 +/- 104.3%, p <0.001). No significant change in percent atheroma volume by IVUS was seen at 12 months in both women and men. In conclusion, statin therapy was effective in both genders for plaque stabilization at 12-month follow-up. High-intensity statin therapy may be particularly important in men. (C) 2016 Elsevier Inc. All rights reserved. C1 [Minami, Yoshiyasu; Xing, Lei; Vergallo, Rocco; Soeda, Tsunenari; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Hou, Jingbo; Jia, Haibo; Hu, Sining; Zhang, Shaosong; Yu, Bo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA. [Hou, Jingbo; Jia, Haibo; Hu, Sining; Zhang, Shaosong; Yu, Bo] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China. [Lee, Hang] Chinese Minist Educ, Key Lab Myocardial Ischemia, Harbin, Peoples R China. [Jang, Ik-Kyung] Kyung Hee Univ, Div Cardiol, Seoul, South Korea. RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.; Yu, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA.; Yu, B (reprint author), Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China.; Jang, IK (reprint author), Kyung Hee Univ, Div Cardiol, Seoul, South Korea. EM yubodr@163.com; ijang@mgh.harvard.edu FU National Natural Science Foundation of China, Beijing, China [81330033] FX Dr. Jang's research was supported by "Mr. and Mrs. Michael and Kathryn Park" and by "Mrs. and Mr. Gill and Allan Gray." Dr. Yu has received research grants from the National Natural Science Foundation of China (81330033), Beijing, China. The other authors have no conflicts of interest to disclose. NR 26 TC 0 Z9 0 U1 1 U2 1 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 JUN 15 PY 2016 VL 117 IS 12 BP 1890 EP 1895 DI 10.1016/j.amjcard.2016.03.038 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DP8OY UT WOS:000378758700005 PM 27138187 ER PT J AU Pirl, WF Lennes, IT AF Pirl, William F. Lennes, Inga T. TI Quality of psychosocial services in cancer centers: Today and tomorrow SO CANCER LA English DT Editorial Material AB Data from Zebrack et al's survey of 57 cancer centers in the United States and Canada have led the authors to conclude that cancers centers are performing moderately well in communicating the importance of psychosocial care, identifying patient psychosocial needs, and referring patients to services. This editorial focuses on areas that need further work and places the data in the context of the process of changing practice to improve the quality of care.See also pages 1937-45. C1 [Pirl, William F.] Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, 55 Fruit St, Boston, MA 02114 USA. [Lennes, Inga T.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, 55 Fruit St, Boston, MA 02114 USA. RP Pirl, WF (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, 55 Fruit St, Boston, MA 02114 USA. EM wpirl@partners.org NR 5 TC 0 Z9 0 U1 2 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 JUN 15 PY 2016 VL 122 IS 12 BP 1807 EP 1808 DI 10.1002/cncr.30018 PG 2 WC Oncology SC Oncology GA DP3NR UT WOS:000378402100006 PM 27070658 ER PT J AU Matulonis, UA Harter, P Gourley, C Friedlander, M Vergote, I Rustin, G Scott, C Meier, W Shapira-Frommer, R Safra, T Matei, D Fielding, A Spencer, S Parry, D Grinsted, L Ledermann, JA AF Matulonis, Ursula A. Harter, Philipp Gourley, Charlie Friedlander, Michael Vergote, Ignace Rustin, Gordon Scott, Clare Meier, Werner Shapira-Frommer, Ronnie Safra, Tamar Matei, Daniela Fielding, Anitra Spencer, Stuart Parry, David Grinsted, Lynda Ledermann, Jonathan A. TI Olaparib maintenance therapy in patients with platinum-sensitive, relapsed serous ovarian cancer and a BRCA mutation: Overall survival adjusted for postprogression poly(adenosine diphosphate ribose) polymerase inhibitor therapy SO CANCER LA English DT Article DE BRCA mutation; olaparib; ovarian cancer; overall survival; poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor ID TRIALS AB BACKGROUNDMaintenance treatment with the oral poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor olaparib (Lynparza) in Study 19 (study number, D0810C00019; ClinicalTrials.gov identifier, NCT00753545) significantly improved progression-free survival in comparison with a placebo for patients with platinum-sensitive, relapsed serous ovarian cancer with a BRCA1/2 mutation (BRCAm), but an interim analysis revealed no statistically significant overall survival (OS) benefit. However, 23% of the patients receiving the placebo switched to a PARP inhibitor after progression. To investigate whether this had a confounding effect on OS, this article reports an exploratory post hoc analysis that excluded all patients from sites where 1 or more placebo patients received postprogression PARP inhibitor treatment. METHODSIn Study 19, 136 of the 265 patients receiving olaparib or a placebo had a BRCAm. Sixteen patients treated at 11 of the 82 investigational sites received a PARP inhibitor after progression; these sites were excluded from this analysis, and 97 BRCAm patients at 50 sites were included. OS was assessed with a Cox proportional hazards model analogous to the primary study analysis. A supporting rank-preserving structural failure time (RPSFT) model analysis was undertaken for all 136 BRCAm patients. RESULTSThe OS hazard ratio (HR) was 0.52 (95% confidence interval [CI], 0.28-0.97) for the 97 BRCAm patients, whereas for the interim OS analysis with all 136 BRCAm patients, it was 0.73 (95% CI, 0.45-1.17). The supportive RPSFT analysis HR was approximately 0.66. CONCLUSIONSThe numerical improvement in the OS HR suggests that in Study 19, postprogression PARP inhibitor treatment had a confounding influence on the interim OS analysis for BRCAm patients. There is a degree of uncertainty due to the small sample size and the lack of data maturity. Cancer 2016;122:1844-52. (c) 2016 American Cancer Society. Maintenance therapy with olaparib, a poly(adenosine diphosphate ribose) polymerase inhibitor, in patients with platinum-sensitive, relapsed serous ovarian cancer and a BRCA mutation significantly improves progression-free survival in comparison with a placebo, according to an interim analysis. However, BRCA mutation carriers receiving a placebo who switch to a poly(adenosine diphosphate ribose) polymerase inhibitor after disease progression are suggested by a post hoc analysis to have a confounding influence on the interim overall survival analysis. C1 [Matulonis, Ursula A.] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. [Harter, Philipp] Kliniken Essen Mitte, Essen, Germany. [Gourley, Charlie] Univ Edinburgh, Edinburgh Canc Res UK Ctr, Edinburgh, Midlothian, Scotland. [Friedlander, Michael] Prince Wales Hosp, Randwick, NSW 2031, Australia. [Vergote, Ignace] Univ Leuven, Leuven, Belgium. [Rustin, Gordon] Mt Vernon Hosp, Northwood HA6 2RN, Middx, England. [Scott, Clare] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Meier, Werner] Evangel Hosp, Dusseldorf, Germany. [Shapira-Frommer, Ronnie] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. [Safra, Tamar] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. [Matei, Daniela] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Fielding, Anitra; Spencer, Stuart; Parry, David; Grinsted, Lynda] AstraZeneca, Macclesfield, Cheshire, England. [Ledermann, Jonathan A.] UCL, London, England. RP Matulonis, UA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM ursula_matulonis@dfci.harvard.edu FU AstraZeneca FX This study was sponsored by AstraZeneca. NR 16 TC 6 Z9 6 U1 2 U2 2 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 JUN 15 PY 2016 VL 122 IS 12 BP 1844 EP 1852 DI 10.1002/cncr.29995 PG 9 WC Oncology SC Oncology GA DP3NR UT WOS:000378402100011 PM 27062051 ER PT J AU Lu, FK Calligaris, D Olubiyi, OI Norton, I Yang, WL Santagata, S Xie, XS Golby, AJ Agar, NYR AF Lu, Fa-Ke Calligaris, David Olubiyi, Olutayo I. Norton, Isaiah Yang, Wenlong Santagata, Sandro Xie, X. Sunney Golby, Alexandra J. Agar, Nathalie Y. R. TI Label-Free Neurosurgical Pathology with Stimulated Raman Imaging SO CANCER RESEARCH LA English DT Article ID SCATTERING MICROSCOPY; IN-VIVO; COHERENCE TOMOGRAPHY; CELL-SURVIVAL; TISSUE; GLIOMA; GLIOBLASTOMA; ABNORMALITIES; SENSITIVITY; RESECTION AB The goal of brain tumor surgery is to maximize tumor removal without injuring critical brain structures. Achieving this goal is challenging as it can be difficult to distinguish tumor from nontumor tissue. While standard histopathology provides information that could assist tumor delineation, it cannot be performed iteratively during surgery as freezing, sectioning, and staining of the tissue require too much time. Stimulated Raman scattering (SRS) microscopy is a powerful label-free chemical imaging technology that enables rapid mapping of lipids and proteins within a fresh specimen. This information can be rendered into pathology-like images. Although this approach has been used to assess the density of glioma cells in murine orthotopic xenografts models and human brain tumors, tissue heterogeneity in clinical brain tumors has not yet been fully evaluated with SRS imaging. Here we profile 41 specimens resected from 12 patients with a range of brain tumors. By evaluating large-scale stimulated Raman imaging data and correlating this data with current clinical gold standard of histopathology for 4,422 fields of view, we capture many essential diagnostic hallmarks for glioma classification. Notably, in fresh tumor samples, we observe additional features, not seen by conventional methods, including extensive lipid droplets within glioma cells, collagen deposition in gliosarcoma, and irregularity and disruption of myelinated fibers in areas infiltrated by oligodendroglioma cells. The data are freely available in a public resource to foster diagnostic training and to permit additional interrogation. Our work establishes the methodology and provides a significant collection of reference images for label-free neurosurgical pathology. (C) 2016 AACR. C1 [Lu, Fa-Ke; Calligaris, David; Olubiyi, Olutayo I.; Norton, Isaiah; Golby, Alexandra J.; Agar, Nathalie Y. R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. [Lu, Fa-Ke; Yang, Wenlong; Xie, X. Sunney] Harvard Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Santagata, Sandro] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. [Santagata, Sandro; Agar, Nathalie Y. R.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Golby, Alexandra J.; Agar, Nathalie Y. R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Biol, Boston, MA USA. RP Agar, NYR (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, 221 Longwood Ave,BLI-137, Boston, MA 02115 USA. EM ssantagata@bics.bwh.harvard.edu; xie@chemistry.harvard.edu; agolby@bwh.harvard.edu; Nathalie_Agar@dfci.harvard.edu OI OLUBIYI, OLUTAYO/0000-0002-2803-3686 FU Harvard Catalyst; Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH) [UL1 TR001102]; Harvard University; NIH Director's New Innovator Award [1DP2OD007383-01]; National Center for Image Guided Therapy grant [P41RR019703]; NIH Pathway to Independence K99/R00 Award [1K99EB020749-1] FX Grant Support; This work was funded by Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH Award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic healthcare centers (A.J. Golby, X.S. Xie, N.Y.R. Agar), NIH Director's New Innovator Award (1DP2OD007383-01 to N.Y.R. Agar), the National Center for Image Guided Therapy grant P41RR019703 (A.J. Golby, N.Y.R. Agar.), and NIH Pathway to Independence K99/R00 Award (1K99EB020749-1 to F.-K. Lu). NR 50 TC 2 Z9 2 U1 6 U2 22 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 JUN 15 PY 2016 VL 76 IS 12 BP 3451 EP 3462 DI 10.1158/0008-5472.CAN-16-0270 PG 12 WC Oncology SC Oncology GA DO8VN UT WOS:000378063200004 PM 27197198 ER PT J AU Guerrant, W Kota, S Troutman, S Mandati, V Fallahi, M Stemmer-Rachamimov, A Kissil, JL AF Guerrant, William Kota, Smitha Troutman, Scott Mandati, Vinay Fallahi, Mohammad Stemmer-Rachamimov, Anat Kissil, Joseph L. TI YAP Mediates Tumorigenesis in Neurofibromatosis Type 2 by Promoting Cell Survival and Proliferation through a COX-2-EGFR Signaling Axis SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; PROSTAGLANDIN E-2; TUMOR-SUPPRESSOR; VESTIBULAR SCHWANNOMA; HIPPO PATHWAY; IN-VIVO; GENE-EXPRESSION; ADENOMA GROWTH; CANCER CELLS; ACTIVATION AB The Hippo-YAP pathway has emerged as a major driver of tumorigenesis in many human cancers. YAP is a transcriptional coactivator and while details of YAP regulation are quickly emerging, it remains unknown what downstream targets are critical for the oncogenic functions of YAP. To determine the mechanisms involved and to identify disease-relevant targets, we examined the role of YAP in neurofibromatosis type 2 (NF2) using cell and animal models. We found that YAP function is required for NF2-null Schwann cell survival, proliferation, and tumor growth in vivo. Moreover, YAP promotes transcription of several targets including PTGS2, which codes for COX-2, a key enzyme in prostaglandin biosynthesis, and AREG, which codes for the EGFR ligand, amphiregulin. Both AREG and prostaglandin E-2 converge to activate signaling through EGFR. Importantly, treatment with the COX-2 inhibitor celecoxib significantly inhibited the growth of NF2-null Schwann cells and tumor growth in a mouse model of NF2. (C) 2016 AACR. C1 [Guerrant, William; Kota, Smitha; Troutman, Scott; Mandati, Vinay; Kissil, Joseph L.] Scripps Res Inst, Dept Canc Biol, Jupiter, FL USA. [Fallahi, Mohammad] Scripps Res Inst, Informat Core, Jupiter, FL USA. [Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kissil, JL (reprint author), Scripps Res Inst, 130 Scripps Way, Jupiter, FL 33458 USA. EM jkissil@scripps.edu FU NIH [NS077952, CA124495] FX Grant Support; This work was supported by the NIH (NS077952 and CA124495 to J.L. Kissil). NR 52 TC 1 Z9 1 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 2016 VL 76 IS 12 BP 3507 EP 3519 DI 10.1158/0008-5472.CAN-15-1144 PG 13 WC Oncology SC Oncology GA DO8VN UT WOS:000378063200009 PM 27216189 ER PT J AU Evans, TM Bhattacharya, A Shi, Y Qi, WB Block, TJ Chaudhuri, A Chaudhuri, AR Hawker, K Van Remmen, H AF Evans, Teresa M. Bhattacharya, Arunabh Shi, Yun Qi, Wenbo Block, Travis J. Chaudhuri, Asish Chaudhuri, Alakananda Ray Hawker, Kara Van Remmen, Holly TI Moderate modulation of disease in the G93A model of ALS by the compound 2-(2-hydroxypheny1)-benzoxazole (HBX) SO NEUROSCIENCE LETTERS LA English DT Article DE Amyotrophic lateral sclerosis; Mouse model; Protein aggregation; Denervation; Treatment; Chelation ID AMYOTROPHIC-LATERAL-SCLEROSIS; MUTANT SUPEROXIDE-DISMUTASE; MOTOR-NEURON DISEASE; CONGO-RED; LIPID-PEROXIDATION; OXIDATIVE STRESS; PROTEIN; MICE; AGGREGATION; SOD1 AB Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurological disease characterized by degeneration and death of motor neurons. Aberrant protein aggregation and oxidative stress are implicated in the etiology of ALS; thus preventing propagation of early aggregation events and oxidative damage could be an effective therapy. We tested the effect of dietary supplementation (initiated 40 days of age) with 2-(2-hydroxyphenyl)-benzoxazole (HBX), a compound with metal chelator and anti-aggregation properties, on disease onset, progression and lifespan in the G93A mouse model of ALS. Tests were not sufficiently powerful to detect any change to survival distribution of mice treated with HBX. However, the disease onset was delayed and max lifespan was increased in the treatment group. Additionally, disease progression was moderated as shown by reduced neuromuscular denervation measured by repetitive nerve stimulation. F-2-isoprostanes, a marker of oxidative damage, are elevated in skeletal muscle from G93A mice at onset and this increase is prevented in HBX fed G93A mice. Furthermore, HBX treatment reduced mutant SOD1 protein aggregation in whole spinal cord of G93A mice at disease onset. Overall, our data suggests that HBX may be able to improve the degenerative symptoms of ALS through the prevention of oxidative damage and protein aggregation. Further studies are needed to uncover the mechanistic effects of HBX in ameliorating ALS pathology. (C) 2016 Published by Elsevier Ireland Ltd. C1 [Evans, Teresa M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Bhattacharya, Arunabh] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular Biol, San Antonio, TX 78229 USA. [Bhattacharya, Arunabh] Univ Texas Hlth Sci Ctr San Antonio, Dept Biol Struct, San Antonio, TX 78229 USA. [Shi, Yun; Qi, Wenbo] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Block, Travis J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, San Antonio, TX 78229 USA. [Chaudhuri, Asish] UT Southwestern, Dept Biochem, Dallas, TX USA. [Chaudhuri, Alakananda Ray; Hawker, Kara] Univ Incarnate Word, Dept Chem, San Antonio, TX USA. [Van Remmen, Holly] Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA. [Van Remmen, Holly] Oklahoma City VA Med Ctr, Oklahoma City, OK USA. RP Van Remmen, H (reprint author), Oklahoma Med Res Fdn, Aging & Metab Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM Holly-VanRemmen@omrf.org FU Veterans Administration Merit Review FX This work was supported by a Veterans Administration Merit Review grant to HVR. We acknowledge the support of Drs. Randy Strong and Elizabeth Fernandez with the Interventions Testing Program at UT Health Science Center San Antonio for their help in the HBX formulation and diet preparation. Additionally, we wish to acknowledge Vivian Diaz and the San Antonio Nathan Shock Center for the housing and survival studies. NR 41 TC 1 Z9 1 U1 1 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 EI 1872-7972 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUN 15 PY 2016 VL 624 BP 1 EP 7 DI 10.1016/j.neulet.2016.04.035 PG 7 WC Neurosciences SC Neurosciences & Neurology GA DP3YV UT WOS:000378433200001 PM 27138280 ER PT J AU Patel, MB Jackson, JC Morandi, A Girard, TD Hughes, CG Thompson, JL Kiehl, AL Elstad, MR Wasserstein, ML Goodman, RB Beckham, JC Chandrasekhar, R Dittus, RS Ely, EW Pandharipande, PP AF Patel, Mayur B. Jackson, James C. Morandi, Alessandro Girard, Timothy D. Hughes, Christopher G. Thompson, Jennifer L. Kiehl, Amy L. Elstad, Mark R. Wasserstein, Mitzi L. Goodman, Richard B. Beckham, Jean C. Chandrasekhar, Rameela Dittus, Robert S. Ely, E. Wesley Pandharipande, Pratik P. TI Incidence and Risk Factors for Intensive Care Unit-related Post-traumatic Stress Disorder in Veterans and Civilians SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE post-traumatic stress disorder; intensive care unit; veterans ID LIFE EVENTS QUESTIONNAIRE; ACUTE LUNG INJURY; QUALITY-OF-LIFE; CRITICAL ILLNESS; PROSPECTIVE COHORT; CARDIAC-SURGERY; CRITICALLY-ILL; ICU TREATMENT; SEPTIC SHOCK; DSM-IV AB Rationale: The incidence and risk factors of post-traumatic stress disorder (PTSD) related to the intensive care unit (ICU) experience have not been reported in a mixed veteran and civilian cohort. Objectives: To describe the incidence and risk factors for ICU related PTSD in veterans and civilians. Methods: This is a prospective, observational, multicenter cohort enrolling adult survivors of critical illness after respiratory failure and/or shock from three Veterans Affairs and one civilian hospital. After classifying those with/without preexisting PTSD (i.e., PTSD before hospitalisation), we then assessed all subjects for ICU-related PTSD at 3 and 12 months post hospitalization. Measurements and Main Results: Of 255 survivors, 181 and 160 subjects were assessed for ICU-related PTSD at 3- and 12-month follow-up, respectively. A high probability of ICU-related PTSD was found in up to 10% of patients at either follow-up time point, whether assessed by PTSD Checklist Event-Specific Version (score 50) or item mapping using the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV). In the multivariable regression, preexisting PTSD was independently associated with ICU-related PTSD at both 3 and 12 months (P < 0.001), as was preexisting depression (P < 0.03), but veteran status was not a consistent independent risk factor for ICU-related PTSD (3-month P = 0.01, 12-month P = 0.48). Conclusions: This study found around 1 in 10 ICU survivors experienced ICU-related PTSD (i.e., PTSD anchored to their critical illness) in the year after hospitalization. Preexisting PTSD and depression were strongly associated with ICU-related PTSD. C1 [Patel, Mayur B.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville VA Med Ctr, Surg Serv, Nashville, TN USA. [Patel, Mayur B.] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Hlth Serv Res,Dept Surg, Div Trauma & Surg Crit Care,Vanderbilt Brain Inst, Nashville, TN USA. [Patel, Mayur B.] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Hlth Serv Res, Sect Surg Sci,Vanderbilt Brain Inst,Dept Neurosur, Nashville, TN USA. [Jackson, James C.; Girard, Timothy D.; Dittus, Robert S.; Ely, E. Wesley] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville VA Med Ctr, Geriatr Res Educ & Clin Ctr, Nashville, TN USA. [Jackson, James C.; Girard, Timothy D.; Kiehl, Amy L.; Ely, E. Wesley] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Hlth Serv Res, Div Allergy Pulm & Crit Care Med,Dept Med, Nashville, TN USA. [Jackson, James C.] Vanderbilt Univ, Med Ctr, Dept Psychiat, Nashville, TN USA. [Morandi, Alessandro] Hosp Ancelle, Dept Rehabil & Aged Care Unit, Cremona, Italy. [Morandi, Alessandro] Geriatr Res Grp, Brescia, Italy. [Hughes, Christopher G.; Pandharipande, Pratik P.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville VA Med Ctr, Anesthesia Serv, Nashville, TN USA. [Hughes, Christopher G.; Pandharipande, Pratik P.] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Hlth Serv Res, Div Crit Care,Dept Anesthesiol, Nashville, TN USA. [Thompson, Jennifer L.; Chandrasekhar, Rameela] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA. [Elstad, Mark R.; Wasserstein, Mitzi L.] US Dept Vet Affairs, VA Salt Lake City Hlth Care Syst, George E Wahlen Dept Vet Affairs Med Ctr, Salt Lake City, UT USA. [Elstad, Mark R.] Univ Utah, Sch Med, Dept Internal Med, Div Pulm & Crit Care Med, Salt Lake City, UT USA. [Goodman, Richard B.] US Dept Vet Affairs, VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. [Goodman, Richard B.] Univ Washington, Sch Med, Dept Internal Med, Div Pulm & Crit Care Med, Seattle, WA USA. [Beckham, Jean C.] US Dept Vet Affairs, Med Ctr, Durham Vet Affairs Med Ctr, Vet Affairs Mid Atlantic Mental Illness Res Educ, Durham, NC USA. [Beckham, Jean C.] Duke Univ, Med Ctr, Dept Psychiat, Div Behav Med, Durham, NC 27710 USA. [Dittus, Robert S.] Vanderbilt Univ, Med Ctr, Ctr Hlth Serv Res, Div Gen Internal Med & Publ Hlth, Nashville, TN USA. [Dittus, Robert S.] Vanderbilt Univ, Med Ctr, Dept Med, Ctr Hlth Serv Res, Nashville, TN USA. RP Patel, MB (reprint author), 1211 21st Ave South,404 Med Arts Bldg, Nashville, TN 37212 USA. EM mayur.b.patel@vanderbilt.edu OI Patel, Mayur/0000-0001-5230-0871; Girard, Timothy/0000-0002-9833-4871 FU NCATS NIH HHS [UL1 TR000445]; NHLBI NIH HHS [R01 HL111111]; NIA NIH HHS [K23 AG031322, K23 AG034257, R01 AG027472, R01 AG035117] NR 58 TC 4 Z9 4 U1 1 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUN 15 PY 2016 VL 193 IS 12 BP 1373 EP 1381 DI 10.1164/rccm.201506-1158OC PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO8FF UT WOS:000378017300013 PM 26735627 ER PT J AU Marcus, EA Tokhtaeva, E Turdikulova, S Capri, J Whitelegge, JP Scott, DR Sachs, G Berditchevski, F Vagin, O AF Marcus, Elizabeth A. Tokhtaeva, Elmira Turdikulova, Shahlo Capri, Joseph Whitelegge, Julian P. Scott, David R. Sachs, George Berditchevski, Fedor Vagin, Olga TI Septin oligomerization regulates persistent expression of ErbB2/HER2 in gastric cancer cells SO BIOCHEMICAL JOURNAL LA English DT Article DE endocytosis; ErbB2; gastric cancer; lysosomal degradation; septin; ubiquitylation ID E3 UBIQUITIN LIGASE; ENDOCYTIC DOWN-REGULATION; MAMMALIAN SEPTIN; STIMULATES INTERNALIZATION; PROTEASOMAL ACTIVITY; HELICOBACTER-PYLORI; TYROSINE KINASES; BARRIER FUNCTION; PLASMA-MEMBRANE; ERBB RECEPTORS AB Septins are a family of cytoskeletal GTP-binding proteins that assemble into membrane-associated hetero-oligomers and organize scaffolds for recruitment of cytosolic proteins or stabilization of membrane proteins. Septins have been implicated in a diverse range of cancers, including gastric cancer, but the underlying mechanisms remain unclear. The hypothesis tested here is that septins contribute to cancer by stabilizing the receptor tyrosine kinase ErbB2, an important target for cancer treatment. Septins and ErbB2 were highly over-expressed in gastric cancer cells. Immunoprecipitation followed by MS analysis identified ErbB2 as a septin-interacting protein. Knockdown of septin-2 or cell exposure to forchlorfenuron (FCF), a well-established inhibitor of septin oligomerization, decreased surface and total levels of ErbB2. These treatments had no effect on epidermal growth factor receptor (EGFR), emphasizing the specificity and functionality of the septin-ErbB2 interaction. The level of ubiquitylated ErbB2 at the plasma membrane was elevated in cells treated with FCF, which was accompanied by a decrease in co-localization of ErbB2 with septins at the membrane. Cathepsin B inhibitor, but not bafilomycin or lactacystin, prevented FCF-induced decrease in total ErbB2 by increasing accumulation of ubiquitylated ErbB2 in lysosomes. Therefore, septins protect ErbB2 from ubiquitylation, endocytosis and lysosomal degradation. The FCF-induced degradation pathway is distinct from and additive with the degradation induced by inhibiting ErbB2 chaperone Hsp90. These results identify septins as novel regulators of ErbB2 expression that contribute to the remarkable stabilization of the receptor at the plasma membrane of cancer cells and may provide a basis for the development of new ErbB2-targeting anti-cancer therapies. C1 [Marcus, Elizabeth A.] Univ Calif Los Angeles, DGSOM, Dept Pediat, Los Angeles, CA 90095 USA. [Marcus, Elizabeth A.; Tokhtaeva, Elmira; Scott, David R.; Sachs, George; Vagin, Olga] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. [Tokhtaeva, Elmira; Scott, David R.; Sachs, George; Vagin, Olga] Univ Calif Los Angeles, Dept Physiol, DGSOM, Los Angeles, CA 90095 USA. [Turdikulova, Shahlo] Uzbek Acad Sci, Ctr High Technol, Tashkent 700174, Uzbekistan. [Capri, Joseph; Whitelegge, Julian P.] Univ Calif Los Angeles, NPI Semel Inst, Pasarow Mass Spectrometry Lab, Los Angeles, CA 90024 USA. [Sachs, George] Univ Calif Los Angeles, DGSOM, Dept Med, Los Angeles, CA 90024 USA. [Berditchevski, Fedor] Univ Birmingham, Sch Canc Sci, Birmingham B15 2TT, W Midlands, England. RP Vagin, O (reprint author), VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA.; Vagin, O (reprint author), Univ Calif Los Angeles, Dept Physiol, DGSOM, Los Angeles, CA 90095 USA. EM olgav@ucla.edu OI Turdikulova, Shahlo/0000-0003-0764-2332 FU NIH [K08DK100661, 1R01DK105156-01, R01HL113350]; UCLA Children's Discovery and Innovation Institute (CDI); United States Veteran Administration (USVA) [2I01BX001006] FX This work was supported by the NIH [grant number K08DK100661 (to E.A.M.)]; the UCLA Children's Discovery and Innovation Institute (CDI) (to E.A.M.); the United States Veteran Administration (USVA) [grant number 2I01BX001006 (to G.S.)]; the NIH [grant number 1R01DK105156-01 (to G.S.)]; and the NIH [grant number R01HL113350 (to O.V.)]. NR 86 TC 1 Z9 1 U1 2 U2 2 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD JUN 15 PY 2016 VL 473 BP 1703 EP 1718 DI 10.1042/BCJ20160203 PN 12 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DO7WC UT WOS:000377992700005 PM 27048593 ER PT J AU Dolly, SO Wagner, AJ Bendell, JC Kindler, HL Krug, LM Seiwert, TY Zauderer, MG Lolkema, MP Apt, D Yeh, RF Fredrickson, JO Spoerke, JM Koeppen, H Ware, JA Lauchle, JO Burris, HA de Bono, JS AF Dolly, Saoirse O. Wagner, Andrew J. Bendell, Johanna C. Kindler, Hedy L. Krug, Lee M. Seiwert, Tanguy Y. Zauderer, Marjorie G. Lolkema, Martijn P. Apt, Doris Yeh, Ru-Fang Fredrickson, Jill O. Spoerke, Jill M. Koeppen, Hartmut Ware, Joseph A. Lauchle, Jennifer O. Burris, Howard A., III de Bono, Johann S. TI Phase I Study of Apitolisib (GDC-0980), Dual Phosphatidylinositol-3-Kinase and Mammalian Target of Rapamycin Kinase Inhibitor, in Patients with Advanced Solid Tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID MALIGNANT PLEURAL MESOTHELIOMA; PI3K PATHWAY; PI3K/MTOR INHIBITOR; PROSTATE-CANCER; CLINICAL-TRIALS; SMALL-MOLECULE; HIGH-FREQUENCY; PIK3CA GENE; NECK-CANCER; MUTATIONS AB Purpose: This first-in-human phase I trial assessed the safety, tolerability, and preliminary antitumor activity of apitolisib (GDC-0980), a dual inhibitor of class I PI3K, and mTOR kinases. Experimental Design: Once-daily oral apitolisib was administered to patients with solid tumors for days 1 to 21 or 1 to 28 of 28-day cycles. Pharmacokinetic and pharmacodynamic parameters were assessed. Results: Overall, 120 patients were treated at doses between 2 and 70 mg. The commonest >= G3 toxicities related to apitolisib at the recommended phase 2 dose (RP2D) at 40 mg once daily included hyperglycemia (18%), rash (14%), liver dysfunction (12%), diarrhea (10%), pneumonitis (8%), mucosal inflammation (6%), and fatigue (4%). Dose-limiting toxicities (1 patient each) were G4 fasting hyperglycemia at 40 mg (21/28 schedule) and G3 maculopapular rash and G3 fasting hyperglycemia at 70 mg (21/28 schedule). The pharmacokinetic profile was dose-proportional. Phosphorylated serine-473 AKT levels were suppressed by >= 90% in platelet-rich plasma within 4 hours at the MTD (50 mg). Pharmacodynamic decreases in fluorodeoxyglucose positron emission tomography uptake of > 25% occurred in 66% (21/32) of patients dosed at 40 mg once daily. Evidence of single-agent activity included 10 RECIST partial responses (PR; confirmed for peritoneal mesothelioma, PIK3CA mutant headand-neck cancer, and three pleural mesotheliomas). Conclusions: Apitolisib exhibited dose-proportional pharmacokinetics with target modulation at doses >= 16 mg. TheRP2Dwas 40 mg once-daily 28/28 schedule; severe on-target toxicities were apparent at >= 40 mg, particularly pneumonitis. Apitolisib was reasonably tolerated at 30 mg, the selected dose for pleural mesothelioma patients given limited respiratory reserve. Modest but durable antitumor activity was demonstrated. (C) 2016 AACR. C1 [Dolly, Saoirse O.; Lolkema, Martijn P.; de Bono, Johann S.] Royal Marsden NHS Fdn Trust, Inst Canc Res, Downs Rd, Sutton SM2 5NG, Surrey, England. [Wagner, Andrew J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, 44 Binney St, Boston, MA 02115 USA. [Wagner, Andrew J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Bendell, Johanna C.; Burris, Howard A., III] Sarah Cannon Res Inst Tennessee Oncol, Nashville, TN USA. [Kindler, Hedy L.; Seiwert, Tanguy Y.] Univ Chicago, Hematol Oncol Sect, Gastrointestinal Oncol & Mesothelioma Programs, Chicago, IL 60637 USA. [Krug, Lee M.; Zauderer, Marjorie G.] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, New York, NY USA. [Lolkema, Martijn P.] Erasmus MC, Rotterdam Canc Inst, Dept Med Oncol, Rotterdam, Netherlands. [Apt, Doris; Yeh, Ru-Fang; Fredrickson, Jill O.; Spoerke, Jill M.; Koeppen, Hartmut; Ware, Joseph A.; Lauchle, Jennifer O.] Genentech Inc, San Francisco, CA 94080 USA. RP de Bono, JS (reprint author), Royal Marsden NHS Fdn Trust, Inst Canc Res, Downs Rd, Sutton SM2 5NG, Surrey, England. EM johann.de-bono@icr.ac.uk FU Genentech, Inc.; Experimental Cancer Medicine Center; National Institute for Health Research Biomedical Research Center; NCI, Cancer Research UK; Medical Research Council FX This study was supported by Genentech, Inc. The Royal Marsden and Institute of Cancer Research Drug Development Unit is supported by an Experimental Cancer Medicine Center grant and the National Institute for Health Research Biomedical Research Center grant. Authors have received funding from the NCI, Cancer Research UK, and the Medical Research Council. NR 46 TC 4 Z9 4 U1 1 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 JUN 15 PY 2016 VL 22 IS 12 BP 2874 EP 2884 DI 10.1158/1078-0432.CCR-15-2225 PG 11 WC Oncology SC Oncology GA DO7JO UT WOS:000377958800008 PM 26787751 ER PT J AU Curry, WT Gorrepati, R Piesche, M Sasada, T Agarwalla, P Jones, PS Gerstner, ER Golby, AJ Batchelor, TT Wen, PY Mihm, MC Dranoff, G AF Curry, William T., Jr. Gorrepati, Ramana Piesche, Matthias Sasada, Tetsuro Agarwalla, Pankaj Jones, Pamela S. Gerstner, Elizabeth R. Golby, Alexandra J. Batchelor, Tracy T. Wen, Patrick Y. Mihm, Martin C. Dranoff, Glenn TI Vaccination with Irradiated Autologous Tumor Cells Mixed with Irradiated GM-K562 Cells Stimulates Antitumor Immunity and T Lymphocyte Activation in Patients with Recurrent Malignant Glioma SO CLINICAL CANCER RESEARCH LA English DT Article ID NEWLY-DIAGNOSED GLIOBLASTOMA; GM-CSF; SUPPRESSOR-CELLS; IMMUNOTHERAPY; MELANOMA; BLOCKADE; SURVIVAL; CANCER; TRIAL; BEVACIZUMAB AB Purpose: Recurrent malignant glioma carries a dismal prognosis, and novel therapies are needed. We examined the feasibility and safety of vaccination with irradiated autologous glioma cells mixed with irradiated GM-K562 cells in patients undergoing craniotomy for recurrent malignant glioma. Experimental Design: We initiated a phase I study examining the safety of 2 doses of GM-K562 cells mixed with autologous cells. Primary endpoints were feasibility and safety. Feasibility was defined as the ability for 60% of enrolled subjects to initiate vaccination. Dose-limiting toxicity was assessed via a 3+3 dose-escalation format, examining irradiated tumor cells mixed with 5 x 106 GM-K562 cells or 1 x 107 GM-K562 cells. Eligibility required a priori indication for resection of a recurrent high-grade glioma. We measured biological activity by measuring delayed type hypersensitivity (DTH) responses, humoral immunity against tumor-associated antigens, and T-lymphocyte activation. Results: Eleven patients were enrolled. Sufficient numbers of autologous tumor cells were harvested in 10 patients, all of whom went on to receive vaccine. There were no dose-limiting toxicities. Vaccination strengthened DTH responses to irradiated autologous tumor cells in most patients, and vigorous humoral responses to tumor-associated angiogenic cytokines were seen as well. T-lymphocyte activation was seen with significantly increased expression of CTLA-4, PD-1, 4-1BB, and OX40 by CD4(+) cells and PD-1 and 4-1BB by CD8(+) cells. Activation was coupled with vaccine-associated increase in the frequency of regulatory CD4(+) T lymphocytes. Conclusions: Vaccination with irradiated autologous tumor cells mixed with GM-K562 cells is feasible, well tolerated, and active in patients with recurrent malignant glioma. (C) 2016 AACR. C1 [Curry, William T., Jr.; Gorrepati, Ramana; Agarwalla, Pankaj; Jones, Pamela S.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Curry, William T., Jr.; Gerstner, Elizabeth R.; Batchelor, Tracy T.] Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Y9E, Boston, MA 02114 USA. [Curry, William T., Jr.; Gerstner, Elizabeth R.; Golby, Alexandra J.; Batchelor, Tracy T.; Wen, Patrick Y.; Mihm, Martin C.; Dranoff, Glenn] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Piesche, Matthias; Dranoff, Glenn] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Sasada, Tetsuro; Dranoff, Glenn] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Golby, Alexandra J.] Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St, Boston, MA 02115 USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Div Neurooncol, Boston, MA 02115 USA. [Mihm, Martin C.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Piesche, Matthias] Aarhus Univ, Dept Biomed, Aarhus, Denmark. RP Curry, WT (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Y9E, Boston, MA 02114 USA. EM wcurry@mgh.harvard.edu FU Harold Amos Faculty Development Program of the Robert Wood Johnson Foundation FX W. Curry, MD, was partially supported by a grant from the Harold Amos Faculty Development Program of the Robert Wood Johnson Foundation. NR 42 TC 3 Z9 3 U1 2 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2016 VL 22 IS 12 BP 2885 EP 2896 DI 10.1158/1078-0432.CCR-15-2163 PG 12 WC Oncology SC Oncology GA DO7JO UT WOS:000377958800009 PM 26873960 ER PT J AU Chau, NG Li, YY Jo, VY Rabinowits, G Lorch, JH Tishler, RB Margalit, DN Schoenfeld, JD Annino, DJ Goguen, LA Thomas, T Becker, H Haddad, T Krane, JF Lindeman, NI Shapiro, GI Haddad, RI Hammerman, PS AF Chau, Nicole G. Li, Yvonne Y. Jo, Vickie Y. Rabinowits, Guilherme Lorch, Jochen H. Tishler, Roy B. Margalit, Danielle N. Schoenfeld, Jonathan D. Annino, Don J. Goguen, Laura A. Thomas, Tom Becker, Hailey Haddad, Tyler Krane, Jeffrey F. Lindeman, Neal I. Shapiro, Geoffrey I. Haddad, Robert I. Hammerman, Peter S. TI Incorporation of Next-Generation Sequencing into Routine Clinical Care to Direct Treatment of Head and Neck Squamous Cell Carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID PLATINUM-BASED THERAPY; HUMAN-PAPILLOMAVIRUS; OPEN-LABEL; GENOMIC CHARACTERIZATION; OROPHARYNGEAL CANCER; HIGH-FREQUENCY; TUMOR SAMPLES; LUNG-CANCER; PHASE-II; MUTATIONS AB Purpose: The clinical impact of next-generation sequencing (NGS) in patients with head and neck squamous cell carcinoma (HNSCC) has not been described. We aimed to evaluate the clinical impact of NGS in the routine care of patients with HNSCC and to correlate genomic alterations with clinical outcomes. Experimental Design: Single-center study examining targeted NGS platform used to sequence tumor DNA obtained from 213 HNSCC patients evaluated in outpatient head and neck oncology clinic between August 2011 and December 2014. We correlated tumor genomic profiling results with clinical outcomes. Results: PI3K/RTK pathway activation occurred frequently [activating PIK3CA mutation or amplification (13%), PTEN inactivation (3%), RAS activation (6%), EGFR or ERBB2 activation (9%)]. Alterations in pathways affecting cell-cycle regulation [CCND1 amplification (9%), CDKN2A inactivation (17%), BRCA2 inactivation (2%)] and squamous differentiation NOTCH1 inactivation (8%) andEP300 inactivation (6%)] were identified. PIK3CA amplification (n = 43), not PIK3CA mutation, was associated with significantly poorer progression-free survival (P = 0.0006). Oncogenic RAS mutations (n = 13) were associated with significantly poorer progression-free survival (P = 0.0001) and lower overall survival (P = 0.003). Eight patients with advanced, treatment-refractory HNSCC enrolled on clinical trials matched to tumor profiling results, and 50% achieved a partial response. Conclusions: Incorporation of NGS clinical assays into the routine care of patients with HNSCC is feasible and may readily facilitate enrollment into clinical trials of targeted therapy with a higher likelihood of success. Data can be utilized for discovery of genomic biomarkers of outcome. PIK3CA amplification and RAS mutations were frequently identified and associated with poorer prognosis in this cohort. (C) 2016 AACR. C1 [Chau, Nicole G.; Li, Yvonne Y.; Rabinowits, Guilherme; Lorch, Jochen H.; Becker, Hailey; Haddad, Tyler; Shapiro, Geoffrey I.; Haddad, Robert I.; Hammerman, Peter S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. [Jo, Vickie Y.; Krane, Jeffrey F.; Lindeman, Neal I.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. [Tishler, Roy B.; Margalit, Danielle N.; Schoenfeld, Jonathan D.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02215 USA. [Annino, Don J.; Goguen, Laura A.; Thomas, Tom] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Otolaryngol, Boston, MA 02215 USA. RP Haddad, RI (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.; Hammerman, PS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.; Hammerman, PS (reprint author), Harvard Univ, Sch Med, 450 Brookline Ave, Boston, MA 02215 USA. EM Robert_Haddad@dfci.harvard.edu; Peter_Hammerman@dfci.harvard.edu NR 32 TC 8 Z9 8 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2016 VL 22 IS 12 BP 2939 EP 2949 DI 10.1158/1078-0432.CCR-15-2314 PG 11 WC Oncology SC Oncology GA DO7JO UT WOS:000377958800014 PM 26763254 ER PT J AU Incio, J Tam, J Rahbari, NN Suboj, P McManus, DT Chin, SM Vardam, TD Batista, A Babykutty, S Jung, K Khachatryan, A Hato, T Ligibel, JA Krop, IE Puchner, SB Schlett, CL Hoffmman, U Ancukiewicz, M Shibuya, M Carmeliet, P Soares, R Duda, DG Jain, RK Fukumura, D AF Incio, Joao Tam, Josh Rahbari, Nuh N. Suboj, Priya McManus, Dan T. Chin, Shan M. Vardam, Trupti D. Batista, Ana Babykutty, Suboj Jung, Keehoon Khachatryan, Anna Hato, Tai Ligibel, Jennifer A. Krop, Ian E. Puchner, Stefan B. Schlett, Christopher L. Hoffmman, Udo Ancukiewicz, Marek Shibuya, Masabumi Carmeliet, Peter Soares, Raquel Duda, Dan G. Jain, Rakesh K. Fukumura, Dai TI PIGF/VEGFR-1 Signaling Promotes Macrophage Polarization and Accelerated Tumor Progression in Obesity SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ADIPOSE-TISSUE DEVELOPMENT; BODY-MASS INDEX; PANCREATIC-CANCER; BREAST-CANCER; FACTOR RECEPTOR-1; METASTASIS FORMATION; BONE-MARROW; IN-VIVO; ANGIOGENESIS AB Purpose: Obesity promotes pancreatic and breast cancer progression via mechanisms that are poorly understood. Although obesity is associated with increased systemic levels of placental growth factor (PlGF), the role of PlGF in obesity-induced tumor progression is not known. PlGF and its receptor VEGFR-1 have been shown to modulate tumor angiogenesis and promote tumor-associated macrophage (TAM) recruitment and activity. Here, we hypothesized that increased activity of PlGF/VEGFR-1 signaling mediates obesity-induced tumor progression by augmenting tumor angiogenesis and TAM recruitment/activity. Experimental Design: We established diet-induced obese mouse models of wild-type C57BL/6, VEGFR-1 tyrosine kinase (TK)-null, or PlGF-null mice, and evaluated the role of PlGF/VEGFR-1 signaling in pancreatic and breast cancer mouse models and in human samples. Results: We found that obesity increased TAM infiltration, tumor growth, and metastasis in pancreatic cancers, without affecting vessel density. Ablation of VEGFR-1 signaling prevented obesity-induced tumor progression and shifted the tumor immune environment toward an antitumor phenotype. Similar findings were observed in a breast cancer model. Obesity was associated with increased systemic PlGF, but not VEGF-A or VEGF-B, in pancreatic and breast cancer patients and in various mouse models of these cancers. Ablation of PlGF phenocopied the effects of VEGFR-1-TK deletion on tumors in obese mice. PlGF/VEGFR-1-TK deletion prevented weight gain in mice fed a high-fat diet, but exacerbated hyperinsulinemia. Addition of metformin not only normalized insulin levels but also enhanced antitumor immunity. Conclusions: Targeting PlGF/VEGFR-1 signaling reprograms the tumor immune microenvironment and inhibits obesityinduced acceleration of tumor progression. (C) 2016 AACR. C1 [Incio, Joao; Tam, Josh; Rahbari, Nuh N.; Suboj, Priya; McManus, Dan T.; Chin, Shan M.; Vardam, Trupti D.; Batista, Ana; Babykutty, Suboj; Jung, Keehoon; Khachatryan, Anna; Hato, Tai; Ancukiewicz, Marek; Duda, Dan G.; Jain, Rakesh K.; Fukumura, Dai] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Labs,Dept Radiat Oncol, Boston, MA USA. [Incio, Joao; Soares, Raquel] Univ Porto, Fac Med, Metab Nutr & Endocrinol Grp, I3S,Inst Innovat & Res Heath,Biochem Dept, Rua Campo Alegre 823, P-4100 Oporto, Portugal. [Incio, Joao] Hosp Sao Joao, Dept Internal Med, Oporto, Portugal. [Tam, Josh] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Rahbari, Nuh N.] Tech Univ Dresden, Dept Surg, Dresden, Germany. [Suboj, Priya] St Xaviers Coll, Dept Bot & Biotechnol, Trivandrum, Kerala, India. [McManus, Dan T.] Univ Massachusetts, Boston, MA 02125 USA. [Vardam, Trupti D.] Mayo Clin, Coll Med, Scottsdale, AZ USA. [Babykutty, Suboj] Mar Ivanios Coll, Dept Zool, Trivandrum, Kerala, India. [Hato, Tai] Keio Univ, Sch Med, Dept Surg, Tokyo 160, Japan. [Ligibel, Jennifer A.; Krop, Ian E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ligibel, Jennifer A.; Krop, Ian E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Puchner, Stefan B.; Schlett, Christopher L.; Hoffmman, Udo] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Puchner, Stefan B.] Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, Vienna, Austria. [Schlett, Christopher L.] Univ Heidelberg Hosp, Dept Diagnost & Intervent Radiol, Heidelberg, Germany. [Ancukiewicz, Marek] PAREXEL Int, Billerica, MA USA. [Shibuya, Masabumi] Jobu Univ, Inst Physiol & Med, Gunma, Japan. [Carmeliet, Peter] Katholieke Univ Leuven, Dept Oncol, Vesalius Res Ctr, Lab Angiogenesis & Neurovasc Link, Leuven, Belgium. [Carmeliet, Peter] VIB, Leuven, Belgium. RP Jain, RK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Labs,Dept Radiat Oncol, Boston, MA USA.; Fukumura, D (reprint author), Massachusetts Gen Hosp, 100 Blossom St,Cox 736, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu; dai@steele.mgh.harvard.edu FU NIH [R35-CA197743, CA080124, CA085140, CA096915, CA115767, CA126642]; Lustgarten Foundation; U.S. Department of Defense Breast Cancer Research Innovator Award [W81XWH-10-1-0016]; Warshaw Institute for Pancreatic Cancer Research; Foundation for Science and Technology FX This study was supported in part by the NIH (http://nih.gov/; R35-CA197743, CA080124, CA085140, CA096915, CA115767, CA126642 to R. K. Jain and D. Fukumura), the Lustgarten Foundation (http://www.lustgarten.org/; research grant to R. K. Jain), the U.S. Department of Defense Breast Cancer Research Innovator Award W81XWH-10-1-0016 (research grant to R. K. Jain), the Warshaw Institute for Pancreatic Cancer Research (http://www.massgeneral.org/warshawinstitute/about/; research grant to D. Fukumura), and the Foundation for Science and Technology (http://www.fct.pt/; Portugal, POPH/FSE funding program, fellowship and research grant to J. Incio). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 8 Z9 8 U1 14 U2 19 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 JUN 15 PY 2016 VL 22 IS 12 BP 2993 EP 3004 DI 10.1158/1078-0432.CCR-15-1839 PG 12 WC Oncology SC Oncology GA DO7JO UT WOS:000377958800019 PM 26861455 ER PT J AU Holzel, BK Brunsch, V Gard, T Greve, DN Koch, K Sorg, C Lazar, SW Milad, MR AF Hoelzel, Britta K. Brunsch, Vincent Gard, Tim Greve, Douglas N. Koch, Kathrin Sorg, Christian Lazar, Sara W. Milad, Mohammed R. TI Mindfulness-Based Stress Reduction, Fear Conditioning, and The Uncinate Fasciculus: A Pilot Study SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE LA English DT Article DE mindfulness; meditation; fear conditioning; fear extinction; diffusion tensor imaging; uncinate fasciculus; neuroplasticity ID VENTROMEDIAL PREFRONTAL CORTEX; RANDOMIZED CONTROLLED-TRIAL; MEDITATION PRACTITIONERS; EXTINCTION MEMORY; EMOTION REGULATION; ANXIETY DISORDER; TRAIT ANXIETY; AMYGDALA; RECONSOLIDATION; CONNECTIVITY AB Mindfulness has been suggested to impact emotional learning, but research on these processes is scarce. The classical fear conditioning/extinction/extinction retention paradigm is a well-known method for assessing emotional learning. The present study tested the impact of mindfulness training on fear conditioning and extinction memory and further investigated whether changes in white matter fiber tracts might support such changes. The uncinate fasciculus (UNC) was of particular interest in the context of emotional learning. In this pilot study, 46 healthy participants were quasi-randomized to a Mindfulness-Based Stress Reduction (MBSR, N = 23) or waitlist control (N = 23) group and underwent a two-day fear conditioning, extinction learning, and extinction memory protocol before and after the course or control period. Skin conductance response (SCR) data served to measure the physiological response during conditioning and extinction memory phases. Diffusion tensor imaging (DTI) data were analyzed with probabilistic tractography and analyzed for changes of fractional anisotropy in the UNC. During conditioning, participants were able to maintain a differential response to conditioned vs. not conditioned stimuli following the MBSR course (i.e., higher sensitivity to the conditioned stimuli), while controls dropped the response. Extinction memory results were not interpretable due to baseline differences. MBSR participants showed a significant increase in fractional anisotropy in the UNC, while controls did not (group by time interaction missed significance). Pre-post changes in UNC were correlated with changes in the response to the conditioned stimuli. The findings suggest effects of mindfulness practice on the maintenance of sensitivity of emotional responses and suggest underlying neural plasticity. C1 [Hoelzel, Britta K.; Koch, Kathrin; Sorg, Christian] Tech Univ Munich, Dept Neuroradiol, Klinikum Rechts Isar, D-80290 Munich, Germany. [Hoelzel, Britta K.; Brunsch, Vincent; Gard, Tim; Greve, Douglas N.; Lazar, Sara W.; Milad, Mohammed R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. [Gard, Tim] Univ Zurich Hosp, Inst Complementary & Integrat Med, CH-8091 Zurich, Switzerland. [Gard, Tim] Univ Zurich, Zurich, Switzerland. [Gard, Tim] Univ Zurich, Inst Biomed Engn, TNU, Zurich, Switzerland. [Gard, Tim] ETH, Swiss Fed Inst Technol, Zurich, Switzerland. RP Holzel, BK (reprint author), Tech Univ Munich, Dept Neuroradiol, Klinikum Rechts Isar, D-80290 Munich, Germany.; Holzel, BK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. EM britta.hoelzel@tum.de RI Lazar, Sara/G-3809-2012 OI Lazar, Sara/0000-0003-1126-8363 FU Templeton Positive Neuroscience Award; Mind and Life Varela Award; Kusala Foundation, Berlin; Laura Bassi-Preis from the Technical University of Munich; NlIl award [R01AT006344]; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health; NTH Shared Instrumentation Grant Program; High-End Instrumentation Grant Program; [S10RR023401]; [S10RR023043] FX This work was supported by a Templeton Positive Neuroscience Award to BKH and MRM, a Mind and Life Varela Award to BKH, funding by the Kusala Foundation, Berlin to BKH, a Laura Bassi-Preis from the Technical University of Munich to BKH, and NlIl award R01AT006344 to SWL. This research was carried out at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41 EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. This work also involved the use of instrumentation supported by the NTH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; specifically, grant number(s) S10RR023401, and S10RR023043. NR 70 TC 0 Z9 0 U1 10 U2 21 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5153 J9 FRONT BEHAV NEUROSCI JI Front. Behav. Neurosci. PD JUN 15 PY 2016 VL 10 AR 124 DI 10.3389/fnbeh.2016.00124 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA DO4MV UT WOS:000377758100001 PM 27378875 ER PT J AU Calabrese, SK Magnus, M Mayer, KH Krakower, DS Eldahan, AI Hawkins, LAG Hansen, NB Kershaw, TS Underhill, K Betancourt, JR Dovidio, JF AF Calabrese, Sarah K. Magnus, Manya Mayer, Kenneth H. Krakower, Douglas S. Eldahan, Adam I. Hawkins, Lauren A. Gaston Hansen, Nathan B. Kershaw, Trace S. Underhill, Kristen Betancourt, Joseph R. Dovidio, John F. TI Putting PrEP into Practice: Lessons Learned from Early-Adopting US Providers' Firsthand Experiences Providing HIV Pre-Exposure Prophylaxis and Associated Care SO PLOS ONE LA English DT Article ID UNITED-STATES; ATTITUDES; KNOWLEDGE; WILLINGNESS; ADULTS; RISK; SEX AB Optimizing access to HIV pre-exposure prophylaxis (PrEP), an evidence-based HIV prevention resource, requires expanding healthcare providers' adoption of PrEP into clinical practice. This qualitative study explored PrEP providers' firsthand experiences relative to six commonly-cited barriers to prescription-financial coverage, implementation logistics, eligibility determination, adherence concerns, side effects, and anticipated behavior change (risk compensation)-as well as their recommendations for training PrEP-inexperienced providers. U.S.-based PrEP providers were recruited via direct outreach and referral from colleagues and other participants (2014-2015). One-on-one interviews were conducted in person or by phone, transcribed, and analyzed. The sample (n = 18) primarily practiced in the Northeastern (67%) or Southern (22%) U.S. Nearly all (94%) were medical doctors (MDs), most of whom self-identified as infectious disease specialists. Prior experience prescribing PrEP ranged from 2 to 325 patients. Overall, providers reported favorable experiences with PrEP implementation and indicated that commonly anticipated problems were minimal or manageable. PrEP was covered via insurance or other programs for most patients; however, pre-authorization requirements, laboratory/service provision costs, and high deductibles sometimes presented challenges. Various models of PrEP care and coordination with other providers were utilized, with several providers highlighting the value of clinical staff support. Eligibility was determined through joint decision-making with patients; CDC guidelines were commonly referenced but not considered absolute. Patient adherence was variable, with particularly strong adherence noted among patients who had actively sought PrEP (self-referred). Providers observed minimal adverse effects or increases in risk behavior. However, they identified several barriers with respect to accessing and engaging PrEP candidates. Providers offered a wide range of suggestions regarding content, strategy, and logistics surrounding PrEP training, highlighting sexual history-taking and sexual minority competence as areas to prioritize. These insights from early-adopting PrEP providers may facilitate adoption of PrEP into clinical practice by PrEP-inexperienced providers, thereby improving access for individuals at risk for HIV. C1 [Calabrese, Sarah K.; Eldahan, Adam I.; Hawkins, Lauren A. Gaston; Kershaw, Trace S.; Dovidio, John F.] Yale Univ, Dept Chron Dis Epidemiol, Sch Publ Hlth, New Haven, CT USA. [Calabrese, Sarah K.; Hansen, Nathan B.; Kershaw, Trace S.; Underhill, Kristen; Dovidio, John F.] Yale Univ, Ctr Interdisciplinary Res AIDS, New Haven, CT USA. [Magnus, Manya] George Washington Univ, Milken Inst Sch Publ Hlth, Dept Epidemiol & Biostat, Washington, DC USA. [Mayer, Kenneth H.; Krakower, Douglas S.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Mayer, Kenneth H.; Krakower, Douglas S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Hansen, Nathan B.] Univ Georgia, Dept Hlth Promot & Behav, Coll Publ Hlth, Athens, GA 30602 USA. [Underhill, Kristen] Yale Univ, Sch Law, New Haven, CT 06520 USA. [Betancourt, Joseph R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dispar Solut Ctr, Boston, MA USA. [Dovidio, John F.] Yale Univ, Dept Psychol, New Haven, CT USA. RP Calabrese, SK (reprint author), Yale Univ, Dept Chron Dis Epidemiol, Sch Publ Hlth, New Haven, CT USA.; Calabrese, SK (reprint author), Yale Univ, Ctr Interdisciplinary Res AIDS, New Haven, CT USA. EM sarah.calabrese@yale.edu FU National Institute of Mental Health (NIMH) [K01-MH103080, K01-MH093273, K23-MH098795]; Yale University Center for Interdisciplinary Research on AIDS [P30-MH062294]; Harvard University Center for AIDS Research [P30-AI060354]; National Institutes of Health FX Funding and resources for this research were provided by the National Institute of Mental Health (NIMH; www.nimh.nih.gov) via Award Number K01-MH103080 (SKC) and the Yale University Center for Interdisciplinary Research on AIDS (P30-MH062294). The efforts of SKC, KU, and DSK were supported by the NIMH via Award Numbers K01-MH103080 (SKC), K01-MH093273 (KU), and K23-MH098795 (DSK). Additional support was provided through the Harvard University Center for AIDS Research (P30-AI060354), funded by the National Institutes of Health (http://www.nih.gov). The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH or 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 23 TC 0 Z9 0 U1 4 U2 8 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 JUN 15 PY 2016 VL 11 IS 6 AR e0157324 DI 10.1371/journal.pone.0157324 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DO5LO UT WOS:000377824800047 PM 27304883 ER PT J AU Huik, K Avi, R Pauskar, M Kallas, E Jogeda, EL Karki, T Ruutel, K Talu, A Abel-Ollo, K Uuskula, A Carrillo, A Ahuja, SK He, WJ Lutsar, I AF Huik, Kristi Avi, Radko Pauskar, Merit Kallas, Eveli Jogeda, Ene-Ly Karki, Tonis Ruutel, Kristi Talu, Ave Abel-Ollo, Katri Uuskula, Anneli Carrillo, Andrew Ahuja, Sunil K. He, Weijing Lutsar, Irja TI A CCL5 Haplotype Is Associated with Low Seropositivity Rate of HCV Infection in People Who Inject Drugs SO PLOS ONE LA English DT Article ID HEPATITIS-C VIRUS; RANTES GENE VARIANTS; CD4(+) T-CELLS; CHEMOKINES; EXPRESSION; IL28B; LIVER; TRANSMISSION; POLYMORPHISM; LYMPHOCYTES AB Objective The role of CC chemokine receptor 5 (CCR5) and its ligand CCL5 on the pathogenesis of HIV infection has been well studied but not for HCV infection. Here, we investigated whether CCL5 haplotypes influence HIV and HCV seropositivity among 373 Caucasian people who inject drugs (PWID) from Estonia. Methods Study included 373 PWID; 56% were HIV seropositive, 44% HCV seropositive and 47% coinfected. Four CCL5 haplotypes (A-D) were derived from three CCL5 polymorphisms (rs2107538/rs2280788/rs2280789) typed by Taqman allelic discrimination assays. The data of CCR5 haplotypes were used from our previous study. The association between CCL5 haplotypes with HIV and/or HCV seropositivity was determined using logistic regression analysis. Results Possessing CCL5 haplotype D (defined by rs2107538A/rs2280788G/rs2280789C) decreased the odds of HCV seropositivity compared to those not possessing it (OR = 0.19; 95% CI 0.09-0.40), which remained significant after adjustment to co-variates (OR = 0.08; 95% CI 0.02-0.29). An association of this haplotype with HIV seropositivity was not found. In step-wise logistic regression with backward elimination CCL5 haplotype D and CCR5 HHG*1 had reduced odds for HCV seropositivity (OR = 0.28 95% CI 0.09-0.92; OR = 0.23 95% CI 0.08-0.68, respectively) compared to those who did not possess these haplotypes, respectively. Conclusions Our results suggest that among PWID CCL5 haplotype D and CCR5 HHG*1 independently protects against HCV. Our findings highlight the importance of CCL5 genetic variability and CCL5-CCR5 axis on the susceptibility to HCV. C1 [Huik, Kristi; Avi, Radko; Pauskar, Merit; Kallas, Eveli; Jogeda, Ene-Ly; Karki, Tonis; Lutsar, Irja] Univ Tartu, Inst Biomed & Translat Med, Dept Microbiol, EE-50411 Tartu, Estonia. [Ruutel, Kristi; Abel-Ollo, Katri] Natl Inst Hlth Dev, EE-11619 Tallinn, Estonia. [Talu, Ave; Uuskula, Anneli] Univ Tartu, Inst Family Med & Publ Hlth, EE-50411 Tartu, Estonia. [Carrillo, Andrew; Ahuja, Sunil K.; He, Weijing] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Carrillo, Andrew; Ahuja, Sunil K.; He, Weijing] South Texas Vet Hlth Care Syst, Vet Adm Ctr Personalized Med, San Antonio, TX 78229 USA. RP Huik, K (reprint author), Univ Tartu, Inst Biomed & Translat Med, Dept Microbiol, EE-50411 Tartu, Estonia. EM kristi.huik@ut.ee FU European Union through the European Regional Development Fund; Basic Financing; Target Financing [SF0180004s12]; Institutional research funding of Estonian Ministry of Education and Research [IUT34-24, IUT34-17]; European Commission - project Expanding Network for Comprehensive and Coordinated Action on HIV/AIDS prevention among IDUs and Bridging Population [2005305]; Global Fund; Tuberculosis and Malaria Program "Scaling up the response to HIV in Estonia"; National HIV/AIDS Strategy; US Civilian Research Development Foundation [ESX0-2722-TA-06]; US National Institutes of Health; National Institute on Drug Abuse [R01DA03574]; Archimedes Foundation and Norwegian Financial Mechanism/EEA [EE0016]; Veterans Affairs (VA) Center for AIDS and HIV Infection and VA Center for Personalized Medicine of the South Texas Veterans Health Care System; National Institutes of Health MERIT grant [R37AI046326]; Doris Duke Distinguished Clinical Scientist Award; VA MERIT award; Elizabeth Glaser Pediatric AIDS Foundation; Burroughs Welcome Clinical Scientist Award in Translational Research; Senior Scholar Award from the Max and Minnie Tomerlin Voelcker Fund FX Study was supported by: European Union through the European Regional Development Fund; Basic Financing and the Target Financing (SF0180004s12) and Institutional research funding (IUT34-24, IUT34-17) of Estonian Ministry of Education and Research; European Commission funded project Expanding Network for Comprehensive and Coordinated Action on HIV/AIDS prevention among IDUs and Bridging Population Nr. 2005305 (ENCAP); Global Fund to Fight HIV, Tuberculosis and Malaria Program "Scaling up the response to HIV in Estonia" for 2003-2007; National HIV/AIDS Strategy for 2006-2015; US Civilian Research Development Foundation (grant ESX0-2722-TA-06); US National Institutes of Health, National Institute on Drug Abuse (grant R01DA03574); the Archimedes Foundation and Norwegian Financial Mechanism/EEA (grant EE0016); the Veterans Affairs (VA) Center for AIDS and HIV Infection and VA Center for Personalized Medicine of the South Texas Veterans Health Care System, a National Institutes of Health MERIT grant (R37AI046326), and the Doris Duke Distinguished Clinical Scientist Award to S.K.A. S.K.A. is also supported by a VA MERIT award, the Elizabeth Glaser Pediatric AIDS Foundation, the Burroughs Welcome Clinical Scientist Award in Translational Research and the Senior Scholar Award from the Max and Minnie Tomerlin Voelcker Fund. NR 35 TC 0 Z9 0 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 15 PY 2016 VL 11 IS 6 AR e0156850 DI 10.1371/journal.pone.0156850 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DO5LO UT WOS:000377824800026 PM 27304910 ER PT J AU Lo, AS Mao, XM Mukherjee, EM Ellebrecht, CT Yu, XC Posner, MR Payne, AS Cavacini, LA AF Lo, Agnes S. Mao, Xuming Mukherjee, Eric M. Ellebrecht, Christoph T. Yu, Xiaocong Posner, Marshall R. Payne, Aimee S. Cavacini, Lisa A. TI Pathogenicity and Epitope Characteristics Do Not Differ in IgG Subclass-Switched Anti-Desmoglein 3 IgG1 and IgG4 Autoantibodies in Pemphigus Vulgaris SO PLOS ONE LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; SWAPPED MOLECULES; TARGET; INHIBITION; EXPRESSION; FOLIACEUS; DISEASE; BINDING; REGION; DOMAIN AB Pemphigus vulgaris (PV) is characterized by IgG1 and IgG4 autoantibodies to desmoglein (Dsg) 3, causing suprabasal blistering of skin and mucous membranes. IgG4 is the dominant autoantibody subclass in PV and correlates with disease activity, whereas IgG1 can be associated with remittent disease. It is unknown if switching the same variable region between IgG4 and IgG1 directly impacts pathogenicity. Here, we tested whether three pathogenic PV monoclonal antibodies (mAbs) from three different patients demonstrate differences in antigen affinity, epitope specificity, or pathogenicity when expressed as IgG1 or IgG4. F706 anti-Dsg3 IgG4 and F779 anti-Dsg3 IgG1, previously isolated as heterohybridomas, and Px43, a monovalent anti-Dsg3/Dsg1 IgG antibody isolated by phage display, were subcloned to obtain paired sets of IgG1 and IgG4 mAbs. Using ELISA and cell surface staining assays, F706 and F779 demonstrated similar antigen binding affinities of IgG1 and IgG4, whereas Px43 showed 3- to 8-fold higher affinity of IgG4 versus IgG1 by ELISA, but identical binding affinities to human skin, perhaps due to targeting of a quaternary epitope best displayed in tissues. All 3 mAb pairs targeted the same extracellular cadherin (EC) domain on Dsg3, caused Dsg3 internalization in primary human keratinocytes, and caused suprabasal blisters in human skin at comparable doses. We conclude that switching IgG1 and IgG4 subclasses of pathogenic PV mAbs does not directly affect their antigen binding or pathogenic properties. C1 [Lo, Agnes S.; Yu, Xiaocong; Posner, Marshall R.; Cavacini, Lisa A.] Dana Farber Canc Inst, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. [Lo, Agnes S.; Yu, Xiaocong; Posner, Marshall R.; Cavacini, Lisa A.] Harvard Univ, Sch Med, Boston, MA USA. [Mao, Xuming; Mukherjee, Eric M.; Ellebrecht, Christoph T.; Payne, Aimee S.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Cavacini, Lisa A.] MassBiologics, 460 Walk Hill St, Boston, MA USA. [Posner, Marshall R.] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. RP Cavacini, LA (reprint author), Dana Farber Canc Inst, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA.; Cavacini, LA (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Cavacini, LA (reprint author), MassBiologics, 460 Walk Hill St, Boston, MA USA. EM lisa.cavacini@umassmed.edu FU Dana-Farber Cancer Institute Friends Head and Neck Cancer Research Award; NIAMS/NIH [AR057001, AR064220, P30-AR057217, T32-AR007465, F30-AR065870]; Dermatology Foundation; DFG [EL711/1-1] FX This work was funded by Dana-Farber Cancer Institute Friends Head and Neck Cancer Research Award (ASL and LAC); in part by NIAMS/NIH grants AR057001, AR064220, P30-AR057217 (ASP) and T32-AR007465, F30-AR065870 (EMM); the Dermatology Foundation (XM); and DFG grant EL711/1-1 (CTE). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; We thank Drs. Sosthene Essono, Martin Jadus and Richard Junghans for reviewing this manuscript, and Mark Duval for his assistance with antibody purification and ELISAs. This work was funded by Dana-Farber Cancer Institute Friends Head and Neck Cancer Research Award (ASL and LAC); in part by NIAMS/NIH grants AR057001, AR064220, P30-AR057217 (ASP) and T32-AR007465, F30-AR065870 (EMM); the Dermatology Foundation (XM); and DFG grant EL711/1-1 (CTE). NR 33 TC 0 Z9 0 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 15 PY 2016 VL 11 IS 6 AR e0156800 DI 10.1371/journal.pone.0156800 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DO5LO UT WOS:000377824800023 PM 27304671 ER PT J AU Yassour, M Vatanen, T Siljander, H Hamalainen, AM Harkonen, T Ryhanen, SJ Franzosa, EA Vlamakis, H Huttenhower, C Gevers, D Lander, ES Knip, M Xavier, RJ AF Yassour, Moran Vatanen, Tommi Siljander, Heli Hamalainen, Anu-Maaria Harkonen, Taina Ryhanen, Samppa J. Franzosa, Eric A. Vlamakis, Hera Huttenhower, Curtis Gevers, Dirk Lander, Eric S. Knip, Mikael Xavier, Ramnik J. CA DIABIMMUNE Study Grp TI Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID INTESTINAL MICROBIOME; METABOLIC DYSFUNCTION; OBESITY; DISEASE; HEALTH; LIFE; CONSEQUENCES; RESPONSES; DYNAMICS; ECOLOGY AB The gut microbial community is dynamic during the first 3 years of life, before stabilizing to an adult-like state. However, little is known about the impact of environmental factors on the developing human gut microbiome. We report a longitudinal study of the gut microbiome based on DNA sequence analysis of monthly stool samples and clinical information from 39 children, about half of whom received multiple courses of antibiotics during the first 3 years of life. Whereas the gut microbiome of most children born by vaginal delivery was dominated by Bacteroides species, the four children born by cesarean section and about 20% of vaginally born children lacked Bacteroides in the first 6 to 18 months of life. Longitudinal sampling, coupled with whole-genome shotgun sequencing, allowed detection of strain-level variation as well as the abundance of antibiotic resistance genes. The microbiota of antibiotic-treated children was less diverse in terms of both bacterial species and strains, with some species often dominated by single strains. In addition, we observed short-term composition changes between consecutive samples from children treated with antibiotics. Antibiotic resistance genes carried on microbial chromosomes showed a peak in abundance after antibiotic treatment followed by a sharp decline, whereas some genes carried on mobile elements persisted longer after antibiotic therapy ended. Our results highlight the value of high-density longitudinal sampling studies with high-resolution strain profiling for studying the establishment and response to perturbation of the infant gut microbiome. C1 [Yassour, Moran; Vatanen, Tommi; Vlamakis, Hera; Huttenhower, Curtis; Gevers, Dirk; Lander, Eric S.; Xavier, Ramnik J.] MIT, Broad Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Yassour, Moran; Vatanen, Tommi; Vlamakis, Hera; Huttenhower, Curtis; Gevers, Dirk; Lander, Eric S.; Xavier, Ramnik J.] Harvard Univ, Cambridge, MA 02142 USA. [Yassour, Moran; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Yassour, Moran; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Vatanen, Tommi] Aalto Univ, Sch Sci, Dept Comp Sci, Espoo 02150, Finland. [Siljander, Heli; Harkonen, Taina; Ryhanen, Samppa J.; Knip, Mikael] Univ Helsinki, Childrens Hosp, Stenbackinkatu 11, FIN-00290 Helsinki, Finland. [Siljander, Heli; Harkonen, Taina; Ryhanen, Samppa J.; Knip, Mikael] Helsinki Univ Hosp, Helsinki 00290, Finland. [Siljander, Heli; Harkonen, Taina; Ryhanen, Samppa J.; Knip, Mikael] Univ Helsinki, Res Programs Unit, Diabet & Obes, FIN-00290 Helsinki, Finland. [Siljander, Heli; Knip, Mikael] Tampere Univ Hosp, Dept Pediat, Tampere 33521, Finland. [Hamalainen, Anu-Maaria] Helsinki Univ Hosp, Jorvi Hosp, Dept Pediat, Espoo 02740, Finland. [Franzosa, Eric A.; Huttenhower, Curtis] MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Lander, Eric S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA. [Lander, Eric S.] Folkhalsan Res Ctr, Helsinki 00290, Finland. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Xavier, Ramnik J.] MIT, Ctr Microbiome Informat & Therapeut, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Gevers, Dirk] Janssen Res & Dev, Janssen Human Microbiome Inst, Cambridge, MA 02142 USA. RP Xavier, RJ (reprint author), MIT, Broad Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Xavier, RJ (reprint author), Harvard Univ, Cambridge, MA 02142 USA.; Xavier, RJ (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.; Xavier, RJ (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA.; Xavier, RJ (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.; Xavier, RJ (reprint author), Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA.; Xavier, RJ (reprint author), MIT, Ctr Microbiome Informat & Therapeut, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM xavier@molbio.mgh.harvard.edu OI Ryhanen, Samppa/0000-0003-4431-643X FU Klarman Family Foundation; National Human Genome Research Institute [2U54HG003067-10]; European Union [202063]; Academy of Finland Centre of Excellence in Molecular Systems Immunology and Physiology Research grant [250114]; JDRF; NIH [U54 DK102557, R01 DK092405, P30 DK043351]; Leona M. and Harry B. Helmsley Charitable Trust; Crohn's and Colitis Foundation of America FX M.Y. was supported by the Klarman Family Foundation. E.S.L. was supported by National Human Genome Research Institute grant 2U54HG003067-10. The DIABIMMUNE study (M.K.) was supported by the European Union Seventh Framework Programme FP7/2007-2013 under grant agreement no. 202063 and the Academy of Finland Centre of Excellence in Molecular Systems Immunology and Physiology Research grant decision number 250114, 2012-2017. R.J.X. was supported by funding from JDRF; NIH grants U54 DK102557, R01 DK092405, and P30 DK043351; the Leona M. and Harry B. Helmsley Charitable Trust; and the Crohn's and Colitis Foundation of America. NR 60 TC 27 Z9 28 U1 22 U2 46 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JUN 15 PY 2016 VL 8 IS 343 AR 343ra81 DI 10.1126/scitranslmed.aad0917 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA DO9FP UT WOS:000378090500002 PM 27306663 ER PT J AU Wurster, JI Saavedra, JT Gilmore, MS AF Wurster, Jenna I. Saavedra, Jose T. Gilmore, Michael S. TI Impact of Antibiotic Use on the Evolution of Enterococcus faecium SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material DE Enterococcus faecium; antibiotic; resistance; evolution; microbiome; VRE ID INTESTINAL COLONIZATION; FAECALIS; RESISTANCE; SUSCEPTIBILITY; VIRULENCE; STRAINS C1 [Wurster, Jenna I.; Saavedra, Jose T.; Gilmore, Michael S.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Gilmore, Michael S.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02114 USA. [Wurster, Jenna I.; Saavedra, Jose T.; Gilmore, Michael S.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Gilmore, MS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA.; Gilmore, MS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02114 USA. EM michael_gilmore@meei.harvard.edu OI Wurster, Jenna/0000-0002-3452-2531 FU NIAID NIH HHS [P01 AI083214, R01 AI072360, R01 AI108710] NR 25 TC 2 Z9 2 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 15 PY 2016 VL 213 IS 12 BP 1862 EP 1865 DI 10.1093/infdis/jiv598 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DO0BL UT WOS:000377444300002 PM 26671888 ER PT J AU Gilden, D White, T Boyer, PJ Galetta, KM Hedley-Whyte, ET Frank, M Holmes, D Nagel, MA AF Gilden, Don White, Teresa Boyer, Philip J. Galetta, Kristin M. Hedley-Whyte, E. Tessa Frank, Meredith Holmes, Dawn Nagel, Maria A. TI Varicella Zoster Virus Infection in Granulomatous Arteritis of the Aorta SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE VZV; granulomatous arteritis; granulomatous aortitis ID GIANT-CELL ARTERITIS; TAKAYASU ARTERITIS; TEMPORAL ARTERIES; DNA; CLASSIFICATION; VASCULOPATHY; REACTIVATION; INVOLVEMENT; CRITERIA; GANGLIA AB Granulomatous arteritis characterizes the pathology of giant cell arteritis, granulomatous aortitis, and intracerebral varicella zoster virus (VZV) vasculopathy. Because intracerebral VZV vasculopathy and giant cell arteritis are strongly associated with productive VZV infection in cerebral and temporal arteries, respectively, we evaluated human aortas for VZV antigen and VZV DNA. Using 3 different anti-VZV antibodies, we identified VZV antigen in 11 of 11 aortas with pathologically verified granulomatous arteritis, in 1 of 1 cases of nongranulomatous arteritis, and in 5 of 18 control aortas (28%) obtained at autopsy. The presence of VZV antigen in granulomatous aortitis was highly significant (P = .0001) as compared to control aortas, in which VZV antigen was never associated with pathology, indicating subclinical reactivation. VZV DNA was found in most aortas containing VZV antigen. The frequent clinical, radiological, and pathological aortic involvement in patients with giant cell arteritis correlates with the significant detection of VZV in granulomatous aortitis. C1 [Gilden, Don; White, Teresa; Nagel, Maria A.] Univ Colorado, Sch Med, Dept Neurol, B-182,12700 E 19th Ave,Rm 5014, Aurora, CO 80045 USA. [Gilden, Don] Univ Colorado, Sch Med, Dept Immunol & Microbiol, Aurora, CO 80045 USA. [Frank, Meredith; Holmes, Dawn] Dept Environm Hlth, Off Med Examiner, Denver, CO USA. [Boyer, Philip J.] E Carolina Univ, Dept Pathol, Greenville, NC USA. [Galetta, Kristin M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Galetta, Kristin M.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Hedley-Whyte, E. Tessa] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Gilden, D (reprint author), Univ Colorado, Sch Med, Dept Neurol, B-182,12700 E 19th Ave,Rm 5014, Aurora, CO 80045 USA. EM don.gilden@ucdenver.edu FU National Institutes of Health [AG032958] FX This work was supported by the National Institutes of Health (grant AG032958 to D. G. and M. A. N.). NR 23 TC 2 Z9 2 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 15 PY 2016 VL 213 IS 12 BP 1866 EP 1871 DI 10.1093/infdis/jiw101 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DO0BL UT WOS:000377444300003 PM 27037084 ER PT J AU Sun, LM Hinrichs, H AF Sun, Limin Hinrichs, Hermann TI Moving average template subtraction to remove stimulation artefacts in EEGs and LFPs recorded during deep brain stimulation SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE DBS artefact removal; Moving Average Subtraction; Resampling ID TREATMENT-RESISTANT DEPRESSION; VISUAL-EVOKED POTENTIALS; PARKINSONS-DISEASE; SUBTHALAMIC NUCLEUS; STIMULUS ARTIFACT; PSYCHIATRIC-DISORDERS AB Background: Deep brain stimulation (DBS) is a well established therapy to treat movement disorders such as Parkinson's disease. More recently it has also been discussed as a therapy for certain psychiatric diseases. However, during active DBS the recordings of local field potentials (LFP) and the electroencephalogram (EEG) can be corrupted by substantial spike-type artefacts which need to be removed before any analysis. New method: Here, we present a new method that we term 'Moving Average Subtraction' (MAS) that removes DBS artefacts by subtracting adaptive DBS artefact templates from the artefact contaminated data. In particular we have developed a resampling technique which is more efficient than upsampling for a precise reconstruction of the artefact shape without the need to oversample the EEGs. Results: By applying this method we can derive undistorted signals even in case of the low sampling frequencies that are usual in clinical recordings. We applied the new technique to 12 data sets recorded at the surface and in various brain structures [subthalamic nucleus (STN), pedunculo pontine nucleus (PPN), Globus pallidus internus (GPi)] with 7 patients. Our results demonstrate the suppression of artefact related activity at the basic and harmonic frequencies of DBS. Comparison with existing method(s): The new technique outperforms the non-adaptive template subtraction technique for the removal of high frequency artefact residuals without producing the spectral dips that occur with notch filter approaches. Conclusions: The new technique facilitates the analysis of higher frequency bands (Gamma activity) in LFPs and EEGs recorded during active DBS. (C) 2016 Elsevier B.V. All rights reserved. C1 [Sun, Limin] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. [Sun, Limin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Cambridge, MA 02129 USA. [Hinrichs, Hermann] Otto Von Guericke Univ, Dept Neurol, Leipziger Str 44, D-39120 Magdeburg, Germany. [Hinrichs, Hermann] LIN, Brenneckestr 6, D-39118 Magdeburg, Germany. [Hinrichs, Hermann] DZNE, Leipziger Str 44, D-39120 Magdeburg, Germany. [Hinrichs, Hermann] Forsch Campus STIMULATE, Sandtorstr 23, D-39106 Magdeburg, Germany. [Hinrichs, Hermann] CBBS, Leipziger Str 44, D-39120 Magdeburg, Germany. RP Hinrichs, H (reprint author), Otto Von Guericke Univ, Dept Neurol, Leipziger Str 44, D-39120 Magdeburg, Germany. EM Hermann.Hinrichs@med.ovgu.de FU BMBF 'Forschungscampus STIMULATE', TP 'Instrumente' [03FO16102A]; DFG [SFB 779, TP A11] FX This project was supported by; (i) BMBF 'Forschungscampus STIMULATE', TP 'Instrumente', 03FO16102A,; (ii) DFG SFB 779, TP A11. NR 32 TC 0 Z9 0 U1 8 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 EI 1872-678X J9 J NEUROSCI METH JI J. Neurosci. Methods PD JUN 15 PY 2016 VL 266 BP 126 EP 136 DI 10.1016/j.jneumeth.2016.03.020 PG 11 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DN8GJ UT WOS:000377316900012 PM 27039973 ER PT J AU Graham, ZA Collier, L Peng, YZ Saez, JC Bauman, WA Qin, WP Cardozo, CP AF Graham, Zachary A. Collier, Lauren Peng, Yuanzhen Saez, Juan C. Bauman, William A. Qin, Weiping Cardozo, Christopher P. TI A Soluble Activin Receptor IIB Fails to Prevent Muscle Atrophy in a Mouse Model of Spinal Cord Injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE inflammation; metabolism; neural injury; spinal cord injury ID BONE-MINERAL DENSITY; MYOSTATIN INHIBITION; BODY-COMPOSITION; GENE-EXPRESSION; GROWING RATS; FIBER-TYPE; MICE; MASS; TRANSECTION; STIMULATION AB Myostatin (MST) is a potent regulator of muscle growth and size. Spinal cord injury (SCI) results in marked atrophy of muscle below the level of injury. Currently, there is no effective pharmaceutical treatment available to prevent sublesional muscle atrophy post-SCI. To determine whether inhibition of MST with a soluble activin IIB receptor (RAP-031) prevents sublesional SCI-induced muscle atrophy, mice were randomly assigned to the following groups: Sham-SCI; SCI+Vehicle group (SCI-VEH); and SCI+RAP-031 (SCI-RAP-031). SCI was induced by complete transection at thoracic level 10. Animals were euthanized at 56 days post-surgery. RAP-031 reduced, but did not prevent, body weight loss post-SCI. RAP-031 increased total lean tissue mass compared to SCI-VEH (14.8%). RAP-031 increased forelimb muscle mass post-SCI by 38% and 19% for biceps and triceps, respectively (p < 0.001). There were no differences in hindlimb muscle weights between the RAP-031 and SCI-VEH groups. In the gastrocnemius, messenger RNA (mRNA) expression was elevated for interleukin (IL)-6 (8-fold), IL-1 beta (3-fold), and tumor necrosis factor alpha (8-fold) in the SCI-VEH, compared to the Sham group. Muscle RING finger protein 1 mRNA was 2-fold greater in the RAP-031 group, compared to Sham-SCI. RAP-031 did not influence cytokine expression. Bone mineral density of the distal femur and proximal tibia were decreased post-SCI (-26% and -28%, respectively) and were not altered by RAP-031. In conclusion, MST inhibition increased supralesional muscle mass, but did not prevent sublesional muscle or bone loss, or the inflammation in paralyzed muscle. C1 [Graham, Zachary A.; Collier, Lauren; Peng, Yuanzhen; Bauman, William A.; Qin, Weiping; Cardozo, Christopher P.] James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. [Bauman, William A.; Cardozo, Christopher P.] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA. [Saez, Juan C.] Pontificia Univ Catolica Chile, Dept Physiol, Alameda 340, Santiago, Chile. [Saez, Juan C.] Ctr Interdisciplinario Neurociencias Valparais, Valparaiso, Chile. [Graham, Zachary A.; Bauman, William A.; Qin, Weiping; Cardozo, Christopher P.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Bauman, William A.; Cardozo, Christopher P.] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. [Cardozo, Christopher P.] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. RP Cardozo, CP (reprint author), James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM christopher.cardozo@mssm.edu FU Department of Veterans Affairs Rehabilitation Research and Development Service [B9212C]; James J. Peters VA Medical Center; Fondecyt [1111033]; Chilean Science Millennium Institute [P09-022-F] FX This work was supported by the Department of Veterans Affairs Rehabilitation Research and Development Service (B9212C), the James J. Peters VA Medical Center, and a Fondecyt project 1111033 (to J.C.S.), Chilean Science Millennium Institute (P09-022-F; to J.C.S.). The authors are grateful to Scott Pearsall and Ravi Kumar for their comments regarding study design and critical reading of the manuscript. RAP-031 was a generous gift from Acceleron Pharma (Cambridge MA). NR 47 TC 1 Z9 1 U1 3 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JUN 15 PY 2016 VL 33 IS 12 BP 1128 EP 1135 DI 10.1089/neu.2015.4058 PG 8 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA DN9WT UT WOS:000377432100003 PM 26529111 ER PT J AU Roussos, P Giakoumaki, SG Zouraraki, C Fullard, JF Karagiorga, VE Tsapakis, EM Petraki, Z Siever, LJ Lencz, T Malhotra, A Spanaki, C Bitsios, P AF Roussos, Panos Giakoumaki, Stella G. Zouraraki, Chrysoula Fullard, John F. Karagiorga, Vasiliki-Eirini Tsapakis, Eva-Maria Petraki, Zoe Siever, Larry J. Lencz, Todd Malhotra, Anil Spanaki, Cleanthe Bitsios, Panos TI The Relationship of Common Risk Variants and Polygenic Risk for Schizophrenia to Sensorimotor Gating SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Baseline startle; Endophenotypes; eQTL; GWAS; Heritability; Prepulse inhibition ID ACOUSTIC STARTLE RESPONSE; GENOME-WIDE ASSOCIATION; PREPULSE INHIBITION; VAL(158)MET POLYMORPHISM; HEALTHY-VOLUNTEERS; REFLEX; HERITABILITY; MODULATION; CONSORTIUM; DEFICITS AB BACKGROUND: Prepulse inhibition (PPI) of the startle reflex has been suggested as a candidate endophenotype for schizophrenia research, as it shows high heritability and has been found deficient in schizophrenia spectrum disorders. The objectives of the study were to 1) identify common genetic variants associated with baseline startle and PPI; 2) estimate the single nucleotide polymorphism heritability; and 3) examine the relationship of polygenic score for schizophrenia with baseline startle and PPI. METHODS: A cohort of healthy young male subjects (n = 1493) originating from the Learning on Genetics of Schizophrenia Spectrum project was assessed for baseline startle and PPI. The most recent genome-wide association study in schizophrenia from the Psychiatric Genomics Consortium 2 was used to calculate polygenic scores. RESULTS: Eleven loci showed suggestive association (p < 10(-6)) with baseline startle and PPI in the discovery cohort. Additional genotyping in a replication cohort identified genome-wide significant association at two loci (rs61810702 and rs4718984). These loci were co-localized with expression quantitative trait loci associated with gene expression of nerve growth factor (NGF) and calneuron 1 (CALN1) genes. Estimation of the genetic and environmental contributions to baseline startle and PPI showed a substantial single nucleotide polymorphism heritability for 120-ms PPI stimuli. Increased polygenic risk score for schizophrenia was associated with reduced PPI. CONCLUSIONS: Common genetic variation has an important role in the etiology of schizophrenia and PPI impairments. Overall, these data support the idea that PPI is a valid endophenotype that can be used to explore the genetic architecture of schizophrenia. C1 [Roussos, Panos] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Roussos, Panos; Fullard, John F.; Karagiorga, Vasiliki-Eirini; Siever, Larry J.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Roussos, Panos] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, New York, NY 10029 USA. [Roussos, Panos; Fullard, John F.; Karagiorga, Vasiliki-Eirini] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Roussos, Panos; Siever, Larry J.] Mental Illness Res Educ & Clin Ctr, James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Giakoumaki, Stella G.; Zouraraki, Chrysoula] Univ Crete, Dept Psychol, Rethimnon, Greece. [Tsapakis, Eva-Maria] Aghios Charalambos Mental Hlth Ctr, Iraklion, Greece. [Petraki, Zoe; Spanaki, Cleanthe] Univ Crete, Fac Med, Dept Neurol, Iraklion, Crete, Greece. [Lencz, Todd; Malhotra, Anil] Zucker Hillside Hosp, Div Psychiat Res, Glen Oaks, NY USA. [Lencz, Todd; Malhotra, Anil] Fenstein Inst Med Res, Ctr Psychiat Neurosci, Manhasset, NY USA. [Lencz, Todd; Malhotra, Anil] Hofstra Univ, Sch Med, Dept Psychiat, Hempstead, NY 11550 USA. [Lencz, Todd; Malhotra, Anil] Hofstra Univ, Sch Med, Dept Mol Med, Hempstead, NY 11550 USA. [Bitsios, Panos] Univ Crete, Fac Med, Dept Psychiat, Iraklion, Crete, Greece. RP Roussos, P (reprint author), Icahn Sch Med, Friedman Brain Inst, Inst Multiscale Biol, Dept Psychiat,Dept Genet & Genom Sci, 1470 Madison Ave, New York, NY USA. EM panagiotis.roussos@mssm.edu RI Roussos, Panos/J-7090-2013; Lencz, Todd/J-3418-2014 OI Roussos, Panos/0000-0002-4640-6239; Lencz, Todd/0000-0001-8586-338X FU Veterans Affairs Merit Grant [BX002395]; Brain Behavior Research Foundation; American Psychiatric Association-Merck & Co. Early Academic Career Research Award; Friedman Brain Institute at Icahn School of Medicine at Mount Sinai; Icahn Institute for Genomics and Multiscale Biology at Icahn School of Medicine at Mount Sinai FX We acknowledge funding support from Veterans Affairs Merit Grant Nos. BX002395 (to PR), the Brain Behavior Research Foundation (to PR), the American Psychiatric Association-Merck & Co. Early Academic Career Research Award (to PR), the Friedman Brain Institute at Icahn School of Medicine at Mount Sinai, and the Icahn Institute for Genomics and Multiscale Biology at Icahn School of Medicine at Mount Sinai. This work was supported in part through the computational resources and staff expertise provided by the Department of Scientific Computing at the Icahn School of Medicine at Mount Sinai. NR 59 TC 5 Z9 5 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 15 PY 2016 VL 79 IS 12 BP 988 EP 996 DI 10.1016/j.biopsych.2015.06.019 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DN0ZV UT WOS:000376796500009 PM 26212897 ER PT J AU Barch, DM Gotlib, IH Bilder, RM Pine, DS Smoller, JW Brown, CH Huggins, W Hamilton, C Haim, A Farber, GK AF Barch, Deanna M. Gotlib, Ian H. Bilder, Robert M. Pine, Daniel S. Smoller, Jordan W. Brown, C. Hendricks Huggins, Wayne Hamilton, Carol Haim, Adam Farber, Gregory K. TI Common Measures for National Institute of Mental Health Funded Research SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID DIFFICULTIES QUESTIONNAIRE SDQ; LIFE EVENTS QUESTIONNAIRE; SELF-REPORT VERSION; PSYCHOMETRIC PROPERTIES; HIPPOCAMPAL VOLUMES; PHENX MEASURES; CDE PROJECT; HIGH-RISK; STRENGTHS; PSYCHOSIS C1 [Barch, Deanna M.] Washington Univ, Dept Psychol, Box 1125,One Brookings Dr, St Louis, MO 63130 USA. [Barch, Deanna M.] Washington Univ, Dept Psychiat, Box 1125,One Brookings Dr, St Louis, MO 63130 USA. [Barch, Deanna M.] Washington Univ, Dept Radiol, Box 1125,One Brookings Dr, St Louis, MO 63130 USA. [Gotlib, Ian H.] Stanford Univ, Dept Psychol, Stanford, CA USA. [Bilder, Robert M.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Bilder, Robert M.] Univ Calif Los Angeles, Dept Biobehav Sci & Psychol, Los Angeles, CA USA. [Pine, Daniel S.] NIMH, Intramural Res Program, Bethesda, MD 20892 USA. [Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Smoller, Jordan W.] Broad Inst, Stanley Ctr Psychiat Res, Boston, MA USA. [Brown, C. Hendricks] Northwestern Univ, Dept Psychiat, Chicago, IL 60611 USA. [Huggins, Wayne; Hamilton, Carol] RTI Int, Durham, NC USA. [Haim, Adam] NIMH, Off Clin Res, Bethesda, MD 20892 USA. [Farber, Gregory K.] NIMH, Off Technol Dev & Coordinat, Bethesda, MD 20892 USA. RP Barch, DM (reprint author), Washington Univ, Dept Psychol, Box 1125,One Brookings Dr, St Louis, MO 63130 USA.; Barch, DM (reprint author), Washington Univ, Dept Psychiat, Box 1125,One Brookings Dr, St Louis, MO 63130 USA.; Barch, DM (reprint author), Washington Univ, Dept Radiol, Box 1125,One Brookings Dr, St Louis, MO 63130 USA. EM dbarch@wustl.edu OI Brown, C Hendricks/0000-0002-0294-2419 FU NHGRI NIH HHS [U41 HG007050]; NICHD NIH HHS [U54 HD087011]; NIMH NIH HHS [K24 MH094614, R01 MH040859, R01 MH074849, R01 MH084840, R01 MH090786, R01 MH098454, R01 MH101478, R01 MH101495, U54 MH091657, R01 MH066031] NR 41 TC 0 Z9 0 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 15 PY 2016 VL 79 IS 12 BP E91 EP E96 DI 10.1016/j.biopsych.2015.07.006 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DN0ZV UT WOS:000376796500001 PM 26903402 ER PT J AU Atochin, DN Chernysheva, GA Smolyakova, VI Osipenko, AN Logvinov, SV Zhdankina, AA Sysolyatin, SV Kryukov, YA Anfinogenova, Y Plotnikova, TM Plotnikov, MB AF Atochin, Dmitriy N. Chernysheva, Galina A. Smolyakova, Vera I. Osipenko, Anton N. Logvinov, Sergey V. Zhdankina, Anna A. Sysolyatin, Sergey V. Kryukov, Yuri A. Anfinogenova, Yana Plotnikova, Tatiana M. Plotnikov, Mark B. TI Neuroprotective effects of p-tyrosol after the global cerebral ischemia in rats SO PHYTOMEDICINE LA English DT Article DE p-tyrosol; Pentoxifylline; Global cerebral ischemia; Antioxidant effect; Neuroprotective effect ID OLIVE OIL; REPERFUSION; ANTIOXIDANT; STROKE; CELLS; INHIBITION; SURVIVAL; INJURY; DEATH AB Background: Salidroside is a biologically active compound derived from Rhodiola rosea L. Studies showed that salidroside after i.v. injection is extensively metabolized to p-tyrosol and only trace amounts of salidroside are found in the brain tissue. Objective: The aim of the study was to investigate the neuroprotective effects of p-tyrosol in the global cerebral ischemia-reperfusion (GCI) model. Study design: A total of 103 Wistar rats were assigned to groups of sham-operated (n = 10), control (n = 42), p-tyrosol-treated (n = 36), and pentoxifylline-treated (n = 15) animals. The rats of control, p-tyrosol-treated, and pentoxifylline-treated groups received intravenously 0.9% NaCl solution, 2% solution of p-tyrosol in doses of 5 mg/kg, 10 mg/kg, and 20 mg/kg, and pentoxifylline in a dose of 100 mg/kg, respectively, daily for 5 days. Rats were examined at days 1, 3, and 5 after GCI. After evaluation of neurological deficit, animals were euthanized for morphological and biochemical characterization. Methods: Rats of control, p-tyrosol-treated, and pentoxifylline-treated groups were exposed to three-vessel model of GCI. Neurological deficit, numeric density of neurons in hippocampal CA1 region, and percentage of neurons with focal and total chromatolysis were studied. Biochemical study assessed contents of conjugated dienes and fluorescent products in brain homogenate. Results: In control group, only 50.0% of rats survived by day 5 after the GCI; 38.1% of survived animals had severe neurologic deficit. In brain tissue of PTX-treated rats, the levels of diene conjugates and fluorescent products were 79% and 73%, respectivley, at day 5 compared with control. Differences in diene conjugates were statistically significant compared with control. The survival rate of animals treated with 20 mg/kg p-tyrosol was 82.3% at day 5 after GCI. In p-tyrosol-treated GCI rats, the numeric density of neurons in the hippocampal CA1 region was higher by 31% compared with control. The percentage of neurons with focal and total chromatolysis decreased by 27% and 43%, respectively. At day 5 after GCI, the levels of conjugated dienes and fluorescent products were significantly lower (by 37% and 45%, respectively) in group of animals treated with 20 mg/kg p-tyrosol compared with control. Moderate neuroprotective effects of 5 mg/kg p-tyrosol administration were documented only at day 5 after GCI. In case of 10 mg/kg p-tyrosol administration, neuroprotection was documented sooner: at day 1 or 3 after GCI. However, administration of 5 and 10 mg/kg p-tyrosol did not affect animal survival. Conclusion: Course administration of intravenous p-tyrosol in a dose of 20 mg/kg increased survival, reduced neurological deficit after GCI, attenuated neuronal damage in the hippocampus, and attenuated lipid peroxidation in brain tissue in animals subject to GCI with reperfusion. (C) 2016 Elsevier GmbH. All rights reserved. C1 [Atochin, Dmitriy N.] Harvard Univ, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Sch Med, Charlestown, MA USA. [Atochin, Dmitriy N.] Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Sch Med, Charlestown, MA USA. [Chernysheva, Galina A.; Smolyakova, Vera I.; Plotnikov, Mark B.] Fed State Budgetary Sci Inst, ED Goldberg Inst Pharmacol & Regenerat Med, 3 Lenin St, Tomsk 634028, Russia. [Osipenko, Anton N.; Logvinov, Sergey V.; Zhdankina, Anna A.; Plotnikova, Tatiana M.] Siberian State Med Univ, 2 Moscowsky Trakt, Tomsk 634050, Russia. [Sysolyatin, Sergey V.; Kryukov, Yuri A.] Russian Acad Sci, Siberian Branch, Inst Problems Chem & Energet Technol, 1 Socialisticheskaya St, Biisk, Russia. [Anfinogenova, Yana] Fed State Budgetary Sci Inst, Cardiol Res Inst, 111a Kievskaya St, Tomsk 634012, Russia. [Anfinogenova, Yana] Tomsk Polytech Univ, RASA Ctr Tomsk, 30 Lenin St, Tomsk 634050, Russia. RP Plotnikov, MB (reprint author), Fed State Budgetary Sci Inst, ED Goldberg Inst Pharmacol & Regenerat Med, 3 Lenin St, Tomsk 634028, Russia. EM mbp2001@mail.ru RI Atochin, Dmitriy/Q-3150-2016; Plotnikov, Mark/P-8957-2016; Sysolyatin, Sergey/H-9688-2014; Anfinogenova, Yana/E-7458-2014; OI Sysolyatin, Sergey/0000-0002-1405-171X; Anfinogenova, Yana/0000-0003-1106-0730; Plotnikova, Tatiana/0000-0003-4223-6639 NR 37 TC 0 Z9 0 U1 5 U2 9 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0944-7113 EI 1618-095X J9 PHYTOMEDICINE JI Phytomedicine PD JUN 15 PY 2016 VL 23 IS 7 BP 784 EP 792 DI 10.1016/j.phymed.2016.03.015 PG 9 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA DM7IM UT WOS:000376533500012 PM 27180226 ER PT J AU Mukerji, SS Eichler, FS AF Mukerji, Shibani S. Eichler, Florian S. TI Teaching NeuroImages: Vanishing white matter ovarioleukodystrophy SO NEUROLOGY LA English DT Editorial Material C1 [Mukerji, Shibani S.; Eichler, Florian S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. [Eichler, Florian S.] Massachusetts Gen Hosp, Ctr Rare Neurol Dis, Boston, MA 02114 USA. RP Mukerji, SS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM smukerji@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JUN 14 PY 2016 VL 86 IS 24 BP E248 EP E248 DI 10.1212/WNL.0000000000002764 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA DP8AT UT WOS:000378721000002 PM 27298454 ER PT J AU Ghosh, S Dutta, M Ray, K Fujita, D Bandyopadhyay, A AF Ghosh, Subrata Dutta, Mrinal Ray, Kanad Fujita, Daisuke Bandyopadhyay, Anirban TI A simultaneous one pot synthesis of two fractal structures via swapping two fractal reaction kinetic states SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS LA English DT Article ID CASCADE REACTIONS; MODEL; DENDRIMERS; ENERGY; CATALYSIS; MEMBRANES; DELIVERY; DESIGN AB We introduce a new class of fractal reaction kinetics wherein two or more distinct fractal structures are synthesized as parts of a singular cascade reaction in a single chemical beaker. Two examples: sphere <-> spiral & triangle <-> square fractals, grow 10(6) orders from a single dendrimer (8 nm) to the visible scale. C1 [Ghosh, Subrata; Fujita, Daisuke; Bandyopadhyay, Anirban] Natl Inst Mat Sci, Adv Key Technol Div, 1-2-1 Sengen, Tsukuba, Ibaraki 3050047, Japan. [Ghosh, Subrata] Harvard Univ, Sch Med, Mass Gen Hosp, Mass Gen Inst Neurodegenerat Dis, Boston, MA 02129 USA. [Ghosh, Subrata; Ray, Kanad] Amity Univ, Jaipur, Rajasthan, India. [Dutta, Mrinal] Int Ctr Mat & Nanoarchitectron MANA, 1-1 Namiki, Tsukuba, Ibaraki 3050044, Japan. RP Ghosh, S; Bandyopadhyay, A (reprint author), Natl Inst Mat Sci, Adv Key Technol Div, 1-2-1 Sengen, Tsukuba, Ibaraki 3050047, Japan.; Ghosh, S (reprint author), Harvard Univ, Sch Med, Mass Gen Hosp, Mass Gen Inst Neurodegenerat Dis, Boston, MA 02129 USA.; Ghosh, S (reprint author), Amity Univ, Jaipur, Rajasthan, India. EM ocsgin@gmail.com; anirban.bandyo@gmail.com NR 50 TC 0 Z9 0 U1 1 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9076 EI 1463-9084 J9 PHYS CHEM CHEM PHYS JI Phys. Chem. Chem. Phys. PD JUN 14 PY 2016 VL 18 IS 22 BP 14772 EP 14775 DI 10.1039/c6cp00447d PG 4 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA DP1TY UT WOS:000378273500002 PM 27166589 ER PT J AU Daley, GQ Hyun, I Apperley, JF Barker, RA Benvenisty, N Bredenoord, AL Breuer, CK Caulfield, T Cedars, MI Frey-Vasconcells, J Heslop, HE Jin, Y Lee, RT McCabe, C Munsie, M Murry, CE Piantadosi, S Rao, M Rooke, HM Sipp, D Studer, L Sugarman, J Takahashi, M Zimmerman, M Kimmelman, J AF Daley, George Q. Hyun, Insoo Apperley, Jane F. Barker, Roger A. Benvenisty, Nissim Bredenoord, Annelien L. Breuer, Christopher K. Caulfield, Timothy Cedars, Marcelle I. Frey-Vasconcells, Joyce Heslop, Helen E. Jin, Ying Lee, Richard T. McCabe, Christopher Munsie, Megan Murry, Charles E. Piantadosi, Steven Rao, Mahendra Rooke, Heather M. Sipp, Douglas Studer, Lorenz Sugarman, Jeremy Takahashi, Masayo Zimmerman, Mark Kimmelman, Jonathan TI Setting Global Standards for Stem Cell Research and Clinical Translation: The 2016 ISSCR Guidelines SO STEM CELL REPORTS LA English DT Editorial Material AB The International Society for Stem Cell Research (ISSCR) presents its 2016 Guidelines for Stem Cell Research and Clinical Translation (ISSCR, 2016). The 2016 guidelines reflect the revision and extension of two past sets of guidelines (ISSCR, 2006; ISSCR, 2008) to address new and emerging areas of stem cell discovery and application and evolving ethical, social, and policy challenges. These guidelines provide an integrated set of principles and best practices to drive progress in basic, translational, and clinical research. The guidelines demand rigor, oversight, and transparency in all aspects of practice, providing confidence to practitioners and public alike that stem cell science can proceed efficiently and remain responsive to public and patient interests. Here, we highlight key elements and recommendations in the guidelines and summarize the recommendations and deliberations behind them. C1 [Daley, George Q.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hyun, Insoo] Case Western Reserve Univ, Dept Bioeth, Sch Med, Cleveland, OH 44106 USA. [Apperley, Jane F.] Hammersmith Hosp, Univ London Imperial Coll Sci Technol & Med, Ctr Hematol, Du Cane Rd, London W12 0NN, England. [Barker, Roger A.] John Geest Ctr Brain Repair, Dept Clin Neurosci, Cambridge CB2 0PY, England. [Benvenisty, Nissim] Hebrew Univ Jerusalem, Azrieli Ctr Stem Cells & Genet Res, Dept Genet, IL-91904 Jerusalem, Israel. [Bredenoord, Annelien L.] Univ Med Ctr Utrecht, Julius Ctr, Dept Med Humanities, POB 85500, NL-3508 GA Utrecht, Netherlands. [Breuer, Christopher K.] Nationwide Childrens Hosp, Ctr Cardiovasc Res, Columbus, OH 43215 USA. [Caulfield, Timothy] Univ Alberta, Hlth Law Inst, Edmonton, AB T6G 2H5, Canada. [Cedars, Marcelle I.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94158 USA. [Frey-Vasconcells, Joyce] Frey Vasconcells Consulting, Sykesville, MD 21784 USA. [Heslop, Helen E.] Houston Methodist Hosp, Ctr Cell & Gene Therapy, Baylor Coll Med, Houston, TX 77030 USA. [Heslop, Helen E.] Texas Childrens Hosp, Houston, TX 77030 USA. [Jin, Ying] Chinese Acad Sci, Inst Hlth Sci, Shandong Jiaotong Univ, Sch Med,Shanghai Inst Biol Sci, Shanghai 200025, Peoples R China. [Lee, Richard T.] Harvard Univ, Harvard Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [McCabe, Christopher] Univ Alberta, Dept Emergency Med, Edmonton, AB T6G 2B7, Canada. [Munsie, Megan] Univ Melbourne, Dept Anat & Neurosci, Educat Eth Law & Community Awareness Unit, Stem Cells Australia, Melbourne, Vic 3010, Australia. [Murry, Charles E.] Univ Washington, Dept Pathol, Inst Stem Cell & Regenerat Med, Ctr Cardiovasc Biol, Seattle, WA 98109 USA. [Murry, Charles E.] Univ Washington, Dept Bioengn, Inst Stem Cell & Regenerat Med, Ctr Cardiovasc Biol, Seattle, WA 98109 USA. [Murry, Charles E.] Univ Washington, Dept Med Cardiol, Inst Stem Cell & Regenerat Med, Ctr Cardiovasc Biol, Seattle, WA 98109 USA. [Piantadosi, Steven] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. [Rao, Mahendra] New York Stem Cell Fdn Res Inst, New York, NY 10023 USA. [Rao, Mahendra] Q Therapeut, Salt Lake City, UT 84108 USA. [Rooke, Heather M.] Int Soc Stem Cell Res, Skokie, IL 60077 USA. [Sipp, Douglas] RIKEN, Ctr Dev Biol, Kobe, Hyogo 6500047, Japan. [Sipp, Douglas] Keio Univ, Sch Med, Tokyo 1608582, Japan. [Studer, Lorenz] Mem Sloan Kettering Canc Ctr, Ctr Stem Cell Biol, New York, NY 10065 USA. [Sugarman, Jeremy] Johns Hopkins Berman Inst Bioeth, Baltimore, MD 21205 USA. [Takahashi, Masayo] RIKEN, Ctr Dev Biol, Kobe, Hyogo 6500047, Japan. [Zimmerman, Mark] ViaCyte, San Diego, CA 92121 USA. [Kimmelman, Jonathan] McGill Univ, Biomed Eth Unit, Montreal, PQ H3A 1X1, Canada. RP Daley, GQ (reprint author), Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.; Daley, GQ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.; Kimmelman, J (reprint author), McGill Univ, Biomed Eth Unit, Montreal, PQ H3A 1X1, Canada. EM george.daley@childrens.harvard.edu; jonathan.kimmelman@mcgill.ca OI Munsie, Megan/0000-0003-3588-8321 FU Department of Health [RP-PG-0707-10101]; Medical Research Council [MC_PC_12009]; NHLBI NIH HHS [R01 HL098228, R01 HL128602, R01 HL128847] NR 19 TC 11 Z9 11 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2213-6711 J9 STEM CELL REP JI Stem Cell Rep. PD JUN 14 PY 2016 VL 6 IS 6 BP 787 EP 797 DI 10.1016/j.stemcr.2016.05.001 PG 11 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA DO8KQ UT WOS:000378032600002 PM 27185282 ER PT J AU Mercier, FE Sykes, DB Scadden, DT AF Mercier, Francois E. Sykes, David B. Scadden, David T. TI Single Targeted Exon Mutation Creates a True Congenic Mouse for Competitive Hematopoietic Stem Cell Transplantation: The C57BL/6-CD45.1(STEM) Mouse SO STEM CELL REPORTS LA English DT Article ID CD45 AB Defining the molecular regulators of hematopoietic stem and progenitor cells (HSPCs) requires in vivo functional analyses. Competitive bone marrow transplants (BMTs) compare control and test HSPCs to demonstrate the functional role of a genetic change or chemical perturbation. Competitive BMT is enabled by antibodies that specifically recognize hematopoietic cells from congenic mouse strains due to variants of the cell surface protein CD45, designated CD45.1 and CD45.2. The current congenic competitor strain, B6.SJL-Ptprc(a) Pepc(b)/BoyJ (CD45.1), has a substantial inherent disadvantage in competition against the C57BL/6 (CD45.2) strain, confounding experimental interpretation. Despite backcrossing, the congenic interval over which the B6.SJL-Ptprc(a) Pepc(b)/BoyJ strain differs is almost 40Mb encoding similar to 300 genes. Here, we demonstrate that a single amino acid change determines the CD45.1 epitope. Further, we report on the single targeted exon mutant (STEM) mouse strain, CD45.1(STEM), which is functionally equivalent to CD45.2 cells in competitive BMT. This strain will permit the precise definition of functional roles for candidate genes using in vivo HSPC assays. C1 [Mercier, Francois E.; Sykes, David B.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA. [Mercier, Francois E.; Sykes, David B.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Canc, 185 Cambridge St, Boston, MA 02114 USA. [Mercier, Francois E.; Sykes, David B.; Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Mercier, FE; Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA.; Mercier, FE; Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Canc, 185 Cambridge St, Boston, MA 02114 USA.; Mercier, FE; Scadden, DT (reprint author), Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM fmercier@mgh.harvard.edu; dscadden@mgh.harvard.edu FU Canadian Institutes of Health Research; American Society of Hematology; Leukemia and Lymphoma Foundation; Alex's Lemonade Stand Foundation; Gerald and Darlene Jordan Chair in Medicine at Harvard University; Harvard Stem Cell Institute (HSCI) FX We would like to thank Youmna Kfoury, Jonathan Hoggatt, Jacqueline Bachand, Cam Dung Le, Katrina Maxcy, and Alexa Carver. We would like to thank the staff of ingenious Targeting Laboratories, especially AnnMarie Degruccio and Anne Schirmer. David Tan provided the mouse graphic in Figure 1. Brian D. Sykes created the ribbon structure in Figure 2A. Jiantao Shi helped with the statistical analysis. We would also like to thank the Harvard Stem Cell Institute (HSCI) for the Seed Grant that provided funds for the generation of this mouse strain as well as members of the CRM/HSCI Flow Cytometry Core. F.E.M. was supported by a Clinician-Scientist training award from the Canadian Institutes of Health Research. D.B.S. was supported by the American Society of Hematology, the Leukemia and Lymphoma Foundation, and Alex's Lemonade Stand Foundation. D.T.S. was supported by the Gerald and Darlene Jordan Chair in Medicine at Harvard University. NR 7 TC 4 Z9 4 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2213-6711 J9 STEM CELL REP JI Stem Cell Rep. PD JUN 14 PY 2016 VL 6 IS 6 BP 985 EP 992 DI 10.1016/j.stemcr.2016.04.010 PG 8 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA DO8KQ UT WOS:000378032600018 PM 27185283 ER PT J AU Ansaloni, L Pisano, M Coccolini, F Peitzmann, AB Fingerhut, A Catena, F Agresta, F Allegri, A Bailey, I Balogh, ZJ Bendinelli, C Biffl, W Bonavina, L Borzellino, G Brunetti, F Burlew, CC Camapanelli, G Campanile, FC Ceresoli, M Chiara, O Civil, I Coimbra, R De Moya, M Di Saverio, S Fraga, GP Gupta, S Kashuk, J Kelly, MD Koka, V Jeekel, H Latifi, R Leppaniemi, A Maier, RV Marzi, I Moore, F Piazzalunga, D Sakakushev, B Sartelli, M Scalea, T Stahel, PF Taviloglu, K Tugnoli, G Uraneus, S Velmahos, GC Wani, I Weber, DG Viale, P Sugrue, M Ivatury, R Kluger, Y Gurusamy, KS Moore, EE AF Ansaloni, L. Pisano, M. Coccolini, F. Peitzmann, A. B. Fingerhut, A. Catena, F. Agresta, F. Allegri, A. Bailey, I. Balogh, Z. J. Bendinelli, C. Biffl, W. Bonavina, L. Borzellino, G. Brunetti, F. Burlew, C. C. Camapanelli, G. Campanile, F. C. Ceresoli, M. Chiara, O. Civil, I. Coimbra, R. De Moya, M. Di Saverio, S. Fraga, G. P. Gupta, S. Kashuk, J. Kelly, M. D. Koka, V. Jeekel, H. Latifi, R. Leppaniemi, A. Maier, R. V. Marzi, I. Moore, F. Piazzalunga, D. Sakakushev, B. Sartelli, M. Scalea, T. Stahel, P. F. Taviloglu, K. Tugnoli, G. Uraneus, S. Velmahos, G. C. Wani, I. Weber, D. G. Viale, P. Sugrue, M. Ivatury, R. Kluger, Y. Gurusamy, K. S. Moore, E. E. TI 2016 WSES guidelines on acute calculous cholecystitis SO WORLD JOURNAL OF EMERGENCY SURGERY LA English DT Review DE Acute calcolous cholecystitis; Diagnosis; Cholecystectomy; Biliary tree stones; Surgical risk; Gallbladder percutaneous drainage; Endoscopic ultrasound; Magnetic resonance; Antibiotic; Abdominal infections ID BILE-DUCT STONES; DELAYED LAPAROSCOPIC CHOLECYSTECTOMY; RANDOMIZED CLINICAL-TRIAL; COMPLICATED INTRAABDOMINAL INFECTIONS; PATIENTS PERCUTANEOUS CHOLECYSTOSTOMY; UNCOMPLICATED SYMPTOMATIC GALLSTONES; POPULATION-BASED ANALYSIS; ACUTE ABDOMINAL-PAIN; HIGH-RISK PATIENTS; ELDERLY-PATIENTS AB Acute calculus cholecystitis is a very common disease with several area of uncertainty. The World Society of Emergency Surgery developed extensive guidelines in order to cover grey areas. The diagnostic criteria, the antimicrobial therapy, the evaluation of associated common bile duct stones, the identification of "high risk" patients, the surgical timing, the type of surgery, and the alternatives to surgery are discussed. Moreover the algorithm is proposed: as soon as diagnosis is made and after the evaluation of choledocholitiasis risk, laparoscopic cholecystectomy should be offered to all patients exception of those with high risk of morbidity or mortality. These Guidelines must be considered as an adjunctive tool for decision but they are not substitute of the clinical judgement for the individual patient. C1 [Ansaloni, L.; Pisano, M.; Coccolini, F.; Allegri, A.; Ceresoli, M.; Piazzalunga, D.] Papa Giovanni XXIII Hosp, Gen Surg 1, Piazza OMS 1, I-24127 Bergamo, Italy. [Peitzmann, A. B.] Univ Pittsburgh, Sch Med, Dept Surg, UPMC, Pittsburgh, PA USA. [Fingerhut, A.] Med Univ Graz, Dept Surg Res, Graz, Austria. [Catena, F.] Univ Hosp Parma, Dept Emergency & Trauma Surg, Parma, Italy. [Agresta, F.] Adria Civil Hosp, Dept Gen Surg, Adria, RO, Italy. [Bailey, I.] Southampton Univ Hosp, Southampton, Hants, England. [Balogh, Z. J.; Bendinelli, C.] John Hunter Hosp, Dept Traumatol, Newcastle, NSW, Australia. [Balogh, Z. J.; Bendinelli, C.] Univ Newcastle, Newcastle, NSW 2300, Australia. [Biffl, W.] Univ Hawaii, Sch Med, Queens Med Ctr, Acute Care Surg, Honolulu, HI 96822 USA. [Bonavina, L.] Univ Milan, Sch Med, IRCCS Policlin San Donato, Dept Surg, Milan, Italy. [Borzellino, G.] Univ Verona, I-37100 Verona, Italy. [Brunetti, F.] Univ Paris Est UPEC, Henri Mondor Hosp, AP HP, Unit Digest Hepatopancreatobiliary Surg & Liver T, Creteil, France. [Burlew, C. C.] Univ Colorado, Sch Med, Denver Hlth Med Ctr, Surg Intens Care Unit,Dept Surg, Denver, CO 80202 USA. [Camapanelli, G.] Insubria Univ, Gen Surg Day Surg Ist Clin St Ambrogio, Milan, Italy. [Campanile, F. C.] Osped San Giovanni Decollato Andosilla, Civita Castellana, Italy. [Chiara, O.] Osped Niguarda Ca Granda, Ctr Trauma, Emergency Dept, Milan, Italy. [Civil, I.] Auckland City Hosp, Dept Surg, Auckland, New Zealand. [Coimbra, R.] Univ Calif San Diego Hlth Sci, Div Trauma Surg Crit Care Burns & Acute Care Surg, San Diego, CA USA. [De Moya, M.] Harvard Univ, Cambridge, MA 02138 USA. [Di Saverio, S.; Tugnoli, G.] Maggiore Hosp, Ctr Trauma, Gen Emergency & Trauma Surg, Bologna, Italy. [Fraga, G. P.] Univ Estadual Campinas, Div Trauma Surg, Campinas, SP, Brazil. [Gupta, S.] Govt Med Coll, Dept Surg, Chandigarh, India. [Kashuk, J.] Tel Aviv Univ, Sackler Sch Med, Assia Med Grp, IL-69978 Tel Aviv, Israel. [Kelly, M. D.] Canberra Hosp, Acute Surg Unit, Canberra, ACT, Australia. [Koka, V.] Mozyr City Hosp, Dept Surg, Mozyr, Belarus, Byelarus. [Jeekel, H.] Erasmus MC, Rotterdam, Netherlands. [Latifi, R.] Univ Arizona, Tucson, AZ USA. [Leppaniemi, A.] Meilahti Hosp, Helsinki, Finland. [Maier, R. V.] Univ Washington, Harborview Med Ctr, Dept Surg, Seattle, WA 98104 USA. [Marzi, I.] Goethe Univ Frankfurt, Univ Hosp, Dept Trauma Hand & Reconstruct Surg, D-60054 Frankfurt, Germany. [Moore, F.] Univ Florida, Dept Surg, Gainesville, FL USA. [Sakakushev, B.] St George Med Univ, Univ Hosp, Gen Surg Clin 1, Plovdiv, Bulgaria. [Sartelli, M.] Macerata Hosp, Dept Surg, Macerata, Italy. [Scalea, T.] Univ Maryland, Sch Med, Crit Care Serv, Ctr Shock Trauma, Baltimore, MD 21201 USA. [Stahel, P. F.] Denver Hlth Med Ctr, Denver, CO USA. [Taviloglu, K.; Moore, E. E.] Taviloglu Proctol Ctr, Istanbul, Turkey. [Uraneus, S.] Med Univ Graz, Dept Surg, Graz, Austria. [Velmahos, G. C.] Massachusetts Gen Hosp, Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Wani, I.] DHS, Srinagar, Kashmir, India. [Weber, D. G.] Trauma & Gen Surg & Univ Western Australia, Royal Perth Hosp, Perth, WA, Australia. [Viale, P.] Univ Bologna, S Orsola Malpighi Alma Mater Studiorum, Teaching Hosp, Infect Dis Unit, Bologna, Italy. [Sugrue, M.] Letterkenny Univ Hosp, Donegal, Ireland. [Sugrue, M.] Donegal Clin Res Acad, Donegal, Ireland. [Ivatury, R.] Virginia Commonwealth Univ, Richmond, VA USA. [Kluger, Y.] Div Gen Surg, Rambam Hlth Care Campus, Haifa, Israel. [Gurusamy, K. S.] UCL, Royal Free Campus, London, England. RP Pisano, M (reprint author), Papa Giovanni XXIII Hosp, Gen Surg 1, Piazza OMS 1, I-24127 Bergamo, Italy. EM lansaloni@asst-pg23.it; mpisano@asst-pg23.it; aiace63@gmail.com RI Campanile, Fabio Cesare/G-2831-2012; OI Campanile, Fabio Cesare/0000-0003-3830-634X; Civil, Ian/0000-0002-1371-1114 NR 168 TC 4 Z9 4 U1 12 U2 18 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 JUN 14 PY 2016 VL 11 AR 25 DI 10.1186/s13017-016-0082-5 PG 23 WC Emergency Medicine; Surgery SC Emergency Medicine; Surgery GA DP3HY UT WOS:000378385100001 PM 27307785 ER PT J AU Goto, T Yoshida, K Tsugawa, Y Filbin, MR Camargo, CA Hasegawa, K AF Goto, Tadahiro Yoshida, Kazuki Tsugawa, Yusuke Filbin, Michael R. Camargo, Carlos A., Jr. Hasegawa, Kohei TI Mortality trends in US adults with septic shock, 2005-2011: a serial cross-sectional analysis of nationally-representative data SO BMC INFECTIOUS DISEASES LA English DT Article DE Septic shock; Mortality trends; Vasopressor; Pneumonia; Urinary tract infection; Intra abdominal infection ID SURVIVING SEPSIS CAMPAIGN; CRITICALLY-ILL PATIENTS; INTENSIVE-CARE UNITS; ADMINISTRATIVE DATA; RANDOMIZED-TRIAL; STATES; OUTCOMES; IMPROVEMENT; POPULATION; INFECTION AB Background: We aimed to investigate mortality trends in hospitalized patients with septic shock in the US. To achieve this objective, we tested hypothesis that mortality decreased in patients identified by the code of septic shock while mortality did not change in those with septic shock identified by vasopressor use. Methods: We conducted a serial cross-sectional analysis using Nationwide Inpatient Sample database from 2005 through 2011. First, we identified all adult patients aged >= 18 years hospitalized for septic shock by the following criteria: 1) primary ICD-9 diagnosis of infection plus procedure code for vasopressor use, 2) primary ICD-9 diagnosis of infection plus septic shock in non-primary field, and 3) primary ICD-9 diagnosis of septic shock. Second, we stratified all identified patients by record of vasopressor use. The outcome of interest was year-to-year changes in the in-hospital all-cause mortality. Results: From 2005 to 2011, we identified 109,812 weighted hospitalizations with septic shock. Overall, there was a significant downward trend in in-hospital mortality (from 46 % in 2005 to 42 % in 2011; P-trend = 0.003); the adjusted mortality also decreased significantly (OR for comparison of 2005 with 2011, 0.98; 95 % CI, 0.96-1.00; P < 0.001). In stratified analysis, the mortality trend was not significant in the subgroup with vasopressor use (from 42 % in 2005 to 40 % in 2011; P-trend = 0.57); similarly, the adjusted mortality did not change significantly (OR, 1.01; 95 % CI, 0.97-1.05; P = 0.62). By contrast, there was a downward trend in mortality in the subgroup without vasopressor use (from 47 % in 2005 to 43 % in 2011; P-trend = 0.002); likewise, the adjusted mortality decreased significantly (OR, 0.97; 95 % CI, 0.95-0.99; P = 0.002) Conclusions: From 2005 to 2011, we found a modest decrease in in-hospital mortality among patients identified with septic shock. However, in the subgroup with vasopressor use, we found no significant change in mortality. Our data challenge the conventional wisdom that mortality in this population has improved during the last decade. C1 [Goto, Tadahiro] Univ Fukui Hosp, Dept Emergency Med, Fukui, Japan. [Goto, Tadahiro; Filbin, Michael R.; Camargo, Carlos A., Jr.; Hasegawa, Kohei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Yoshida, Kazuki; Camargo, Carlos A., Jr.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Tsugawa, Yusuke] Harvard Univ, Harvard Interfac Initiat Hlth Policy, Boston, MA USA. RP Goto, T (reprint author), Univ Fukui Hosp, Dept Emergency Med, Fukui, Japan.; Goto, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. EM tgoto1@mgh.harvard.edu OI Yoshida, Kazuki/0000-0002-2030-3549 FU Japan Student Services Organization; Harvard School of Public Health (Pfizer); Harvard School of Public Health (Takeda); Harvard School of Public Health (Bayer); Harvard School of Public Health (PhRMA); Harvard University; Honjo International Scholarship Foundation (Tokyo, Japan) FX Dr. Yoshida receives tuition support jointly from Japan Student Services Organization and Harvard School of Public Health (partially supported by training grants from Pfizer, Takeda, Bayer and PhRMA). Dr. Tsugawa is funded by Harvard University and Honjo International Scholarship Foundation (Tokyo, Japan). This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. NR 42 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD JUN 14 PY 2016 VL 16 AR 294 DI 10.1186/s12879-016-1620-1 PG 8 WC Infectious Diseases SC Infectious Diseases GA DO7GM UT WOS:000377950400002 PM 27301657 ER PT J AU Kennedy, BK Lamming, DW AF Kennedy, Brian K. Lamming, Dudley W. TI The Mechanistic Target of Rapamycin: The Grand ConducTOR of Metabolism and Aging SO CELL METABOLISM LA English DT Review ID MTOR COMPLEX 2; TUBEROUS SCLEROSIS COMPLEX; GLYCOGEN-SYNTHASE ACTIVITY; MESSENGER-RNA TRANSLATION; WHOLE-BODY METABOLISM; MAMMALIAN LIFE-SPAN; SKELETAL-MUSCLE; ADIPOSE-TISSUE; RAG GTPASES; GLUCOSE-HOMEOSTASIS AB Since the discovery that rapamycin, a small molecule inhibitor of the protein kinase mTOR (mechanistic target of rapamycin), can extend the lifespan of model organisms including mice, interest in understanding the physiological role and molecular targets of this pathway has surged. While mTOR was already well known as a regulator of growth and protein translation, it is now clear that mTOR functions as a central coordinator of organismal metabolism in response to both environmental and hormonal signals. This review discusses recent developments in our understanding of how mTOR signaling is regulated by nutrients and the role of the mTOR signaling pathway in key metabolic tissues. Finally, we discuss the molecular basis for the negative metabolic side effects associated with rapamycin treatment, which may serve as barriers to the adoption of rapamycin or similar compounds for the treatment of diseases of aging and metabolism. C1 [Kennedy, Brian K.] Buck Inst Res Aging, Novato, CA 94945 USA. [Lamming, Dudley W.] Univ Wisconsin, Dept Med, Madison, WI 53705 USA. [Lamming, Dudley W.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Lamming, DW (reprint author), Univ Wisconsin, Dept Med, Madison, WI 53705 USA.; Lamming, DW (reprint author), William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. EM dlamming@medicine.wisc.edu FU NIH [R56 AG050441]; K99/R00 Pathway to Independence Award [R00 AG041765]; Wisconsin Partnership Program; Glenn Foundation Award for Research in the Biological Mechanisms of Aging; UW-Madison School of Medicine and Public Health; UW-Madison Department of Medicine; American Federation for Aging Research; Delos Pharmaceuticals FX We thank the reviewers for their thoughtful commentary and critiques. This work was supported in part by NIH grant R56 AG050441 to B.K.K. and a K99/R00 Pathway to Independence Award to D.W.L. (R00 AG041765). D.W.L. is supported in part by a New Investigator Program Award from the Wisconsin Partnership Program, a Glenn Foundation Award for Research in the Biological Mechanisms of Aging, and startup funds from the UW-Madison School of Medicine and Public Health and the UW-Madison Department of Medicine. This review was prepared while D.W.L. was an AFAR Research Grant recipient from the American Federation for Aging Research. This work was supported using facilities and resources from the William S. Middleton Memorial Veterans Hospital. This work does not represent the views of the Department of Veterans Affairs or the United States Government. B.K.K. is the Board Chair of Mount Tam Pharmaceuticals, which seeks to develop novel therapeutics to treat autoimmune diseases by modifying the mTOR pathway. D.W.L has received funding from, and is a scientific advisory board member of, Delos Pharmaceuticals, which seeks to develop novel, selective mTOR inhibitors for the treatment of various diseases. NR 171 TC 17 Z9 18 U1 7 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD JUN 14 PY 2016 VL 23 IS 6 BP 990 EP 1003 DI 10.1016/j.cmet.2016.05.009 PG 14 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA DO7ZA UT WOS:000378000600012 PM 27304501 ER PT J AU Legarda, D Justus, SJ Ang, RL Rikhi, N Li, WJ Moran, TM Zhang, JK Mizoguchi, E Zelic, M Kelliher, MA Blander, M Ting, AT AF Legarda, Diana Justus, Scott J. Ang, Rosalind L. Rikhi, Nimisha Li, Wenjing Moran, Thomas M. Zhang, Jianke Mizoguchi, Emiko Zelic, Matija Kelliher, Michelle A. Blander, Magarian Ting, Adrian T. TI CYLD Proteolysis Protects Macrophages from TNF-Mediated Auto-necroptosis Induced by LPS and Licensed by Type I IFN SO CELL REPORTS LA English DT Article ID MIXED LINEAGE KINASE; RECEPTOR-INTERACTING PROTEIN; DOMAIN-LIKE PROTEIN; NECROTIC CELL-DEATH; TOLL-LIKE RECEPTORS; KAPPA-B ACTIVATION; PROGRAMMED NECROSIS; REGULATORY FACTOR-3; APOPTOSIS; CASPASE-8 AB Tumor necrosis factor (TNF) induces necroptosis, a RIPK3/MLKL-dependent form of inflammatory cell death. In response to infection by Gram-negative bacteria, multiple receptors on macrophages, including TLR4, TNF, and type I IFN receptors, are concurrently activated, but it is unclear how they crosstalk to regulate necroptosis. We report that TLR4 activates CASPASE-8 to cleave and remove the deubiquitinase cylindromatosis (CYLD) in a TRIF-and RIPK1-dependent manner to disable necroptosis in macrophages. Inhibiting CASPASE-8 leads to CYLD-dependent necroptosis caused by the TNF produced in response to TLR4 ligation. While lipopolysaccharides (LPS)-induced necroptosis was abrogated in Tnf(-/-) macrophages, a soluble TNF antagonist was not able to do so in Tnf(+/+) macrophages, indicating that necroptosis occurs in a cellautonomous manner. Surprisingly, TNF-mediated auto-necroptosis of macrophages requires type I IFN, which primes the expression of key necroptosis- signaling molecules, including TNFR2 and MLKL. Thus, the TNF necroptosis pathway is regulated by both negative and positive crosstalk. C1 [Legarda, Diana; Justus, Scott J.; Ang, Rosalind L.; Rikhi, Nimisha; Moran, Thomas M.; Blander, Magarian; Ting, Adrian T.] Icahn Sch Med Mt Sinai, Inst Immunol, New York, NY 10029 USA. [Justus, Scott J.; Blander, Magarian; Ting, Adrian T.] Icahn Sch Med Mt Sinai, Grad Sch Biol Sci, New York, NY 10029 USA. [Li, Wenjing; Moran, Thomas M.; Blander, Magarian] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA. [Li, Wenjing; Moran, Thomas M.] Icahn Sch Med Mt Sinai, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA. [Zhang, Jianke] Thomas Jefferson Univ, Dept Microbiol & Immunol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. [Mizoguchi, Emiko] Massachusetts Gen Hosp, Dept Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Zelic, Matija; Kelliher, Michelle A.] Univ Massachusetts, Sch Med, Dept Mol Cell & Canc Biol, Worcester, MA 01605 USA. [Blander, Magarian; Ting, Adrian T.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Dept Med, New York, NY 10029 USA. RP Ting, AT (reprint author), Icahn Sch Med Mt Sinai, Inst Immunol, New York, NY 10029 USA.; Ting, AT (reprint author), Icahn Sch Med Mt Sinai, Grad Sch Biol Sci, New York, NY 10029 USA.; Ting, AT (reprint author), Icahn Sch Med Mt Sinai, Tisch Canc Inst, Dept Med, New York, NY 10029 USA. EM adrian.ting@mssm.edu FU NIH [AI052417, AI104521, DK072201, DK080070, AI095245, AI075118]; National Institute of Allergy and Infectious Diseases (NIAID) [HHSN272201000054C]; Crohn's and Colitis Foundation of America [253097]; Crohn's and Colitis Foundation of America; Public Health Service Institutional Research Training Award [AI07647]; Helmsley Trust fellowship; Broad Medical Foundation; Burroughs Wellcome Trust Fund; Leukemia and Lymphoma Society; Irma-Hirschl Trust Fund; Monique Weill-Caulier Charitable Trust Fund; NIAID T32 Cross-Disciplinary Training Program in Transplant Research [AI78892] FX We thank Dr. Shizuo Akira, Dr. Douglas Green, Dr. Shao-Cong Sun, and Dr. Adolfo Garcia-Sastre for providing mice and femurs/tibia, Dr. Nicolas Barnich for providing AIEC strain LF82, and Dr. Kate Fitzgerald for providing J2 virus. We would also like to thank Dr. Marie Anne O'Donnell for helpful discussions. This work was supported by NIH grants AI052417, AI104521, DK072201 (A.T.T.), DK080070 (E.M.), AI095245, DK072201 (J.M.B.), AI075118 (M.A.K.), and National Institute of Allergy and Infectious Diseases (NIAID) contract HHSN272201000054C (T.M.M). This work is also supported by a Senior Research Award 253097 from the Crohn's and Colitis Foundation of America (A.T.T.). D.L. is a recipient of a Career Development Award from the Crohn's and Colitis Foundation of America. S.J.J. is supported in part by a Public Health Service Institutional Research Training Award (AI07647) and a Helmsley Trust fellowship. E.M. is supported by a grant from the Broad Medical Foundation (E.M.). J.M.B. is supported by the Burroughs Wellcome Trust Fund, the Leukemia and Lymphoma Society, and the Irma-Hirschl and Monique Weill-Caulier Charitable Trust Funds. R.L.A. is supported by a NIAID T32 Cross-Disciplinary Training Program in Transplant Research (AI78892). NR 67 TC 8 Z9 8 U1 2 U2 3 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 JUN 14 PY 2016 VL 15 IS 11 BP 2449 EP 2461 DI 10.1016/j.celrep.2016.05.032 PG 13 WC Cell Biology SC Cell Biology GA DO4TG UT WOS:000377776400014 PM 27264187 ER PT J AU Kais, Z Rondinelli, B Holmes, A O'Leary, C Kozono, D D'Andrea, AD Ceccaldi, R AF Kais, Zeina Rondinelli, Beatrice Holmes, Amie O'Leary, Colin Kozono, David D'Andrea, Alan D. Ceccaldi, Raphael TI FANCD2 Maintains Fork Stability in BRCA1/2-Deficient Tumors and Promotes Alternative End-Joining DNA Repair SO CELL REPORTS LA English DT Article ID STALLED REPLICATION FORKS; CROSS-LINK REPAIR; FANCONI-ANEMIA PATHWAY; CHROMOSOMAL TRANSLOCATION FORMATION; CLASS-SWITCH RECOMBINATION; DOUBLE-STRAND BREAKS; HOMOLOGOUS-RECOMBINATION; POLYMERASE THETA; MONOUBIQUITINATED FANCD2; GENOMIC INSTABILITY AB BRCA1/2 proteins function in homologous recombination (HR)-mediated DNA repair and cooperate with Fanconi anemia (FA) proteins to maintain genomic integrity through replication fork stabilization. Loss of BRCA1/2 proteins results in DNA repair deficiency and replicative stress, leading to genomic instability and enhanced sensitivity to DNA-damaging agents. Recent studies have shown that BRCA1/2deficient tumors upregulate Polq-mediated alternative end-joining (alt-EJ) repair as a survival mechanism. Whether other mechanisms maintain genomic integrity upon loss of BRCA1/2 proteins is currently unknown. Here we show that BRCA1/2-deficient tumors also upregulate FANCD2 activity. FANCD2 is required for fork protection and fork restart in BRCA1/2-deficient tumors. Moreover, FANCD2 promotes Polq recruitment at sites of damage and altEJ repair. Finally, loss of FANCD2 in BRCA1/2-deficient tumors enhances cell death. These results reveal a synthetic lethal relationship between FANCD2 and BRCA1/2, and they identify FANCD2 as a central player orchestrating DNA repair pathway choice at the replication fork. C1 [Kais, Zeina; Rondinelli, Beatrice; Holmes, Amie; O'Leary, Colin; Kozono, David; D'Andrea, Alan D.; Ceccaldi, Raphael] Harvard Univ, Dana Farber Canc Inst, Dept Radiat Oncol, Sch Med, Boston, MA 02215 USA. [D'Andrea, Alan D.] Dana Farber Canc Inst, Ctr DNA Damage & Repair, Boston, MA 02215 USA. RP D'Andrea, AD; Ceccaldi, R (reprint author), Harvard Univ, Dana Farber Canc Inst, Dept Radiat Oncol, Sch Med, Boston, MA 02215 USA.; D'Andrea, AD (reprint author), Dana Farber Canc Inst, Ctr DNA Damage & Repair, Boston, MA 02215 USA. EM alan_dandrea@dfci.harvard.edu; raphael_ceccaldi@dfci.harvard.edu FU Ovarian Cancer Research Fellowship (OCRF) Ann Shreiber Mentored Investigator Award; Italian Association for Cancer Research (AIRC) Fellowship; Claudia Adams Barr Program award; Stand Up To Cancer (SU2C) - Ovarian Cancer Research Fund-Ovarian Cancer National Alliance-National Ovarian Cancer Coalition Dream Team Translational Research Grant [SU2C-AACR-DT16-15]; American Association for Cancer Research; NIH [R01DK43889, R37HL052725]; Breast Cancer Research Foundation; Fanconi Anemia Research Fund FX We would like to thank R. Drapkin, A. de Fazio, D. Chowdhury, P.A. Konstantinopoulos, K. Strickland, and T. Taniguchi for providing ovarian cell lines; L. Moreau for chromosomal breakage analysis; K.W. O'Connor, K.W. Mouw, and P. Sarangi for critical reading of the manuscript; S.V. Cardenas and K.W. O'Connor for early contributions to the project; and J.B. Lazaro and C. Clairmont for assistance on DNA fiber analysis. We thank A. Constantinou and G. Lossaint for providing the doxycycline-inducible pTripZ shFANCD2 construct and M. Cohn for providing the Poz-N-FANCD2 construct. Z.K. is the recipient of the Ovarian Cancer Research Fellowship (OCRF) Ann Shreiber Mentored Investigator Award and B.R. is a recipient of the Italian Association for Cancer Research (AIRC) Fellowship for Abroad. This research was supported by a Claudia Adams Barr Program award (to R.C.) and a Stand Up To Cancer (SU2C) - Ovarian Cancer Research Fund-Ovarian Cancer National Alliance-National Ovarian Cancer Coalition Dream Team Translational Research Grant (SU2C-AACR-DT16-15). SU2C is a program of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the scientific partner of SU2C. This work also was supported by grants from the NIH (R01DK43889 and R37HL052725), the Breast Cancer Research Foundation, and the Fanconi Anemia Research Fund (to A.D.D.). NR 77 TC 5 Z9 5 U1 3 U2 8 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 JUN 14 PY 2016 VL 15 IS 11 BP 2488 EP 2499 DI 10.1016/j.celrep.2016.05.031 PG 12 WC Cell Biology SC Cell Biology GA DO4TG UT WOS:000377776400017 PM 27264184 ER PT J AU Capellera-Garcia, S Pulecio, J Dhulipala, K Siva, K Rayon-Estrada, V Singbrant, S Sommarin, MNE Walkley, CR Soneji, S Karlsson, G Raya, A Sankaran, VG Flygare, J AF Capellera-Garcia, Sandra Pulecio, Julian Dhulipala, Kishori Siva, Kavitha Rayon-Estrada, Violeta Singbrant, Sofie Sommarin, Mikael N. E. Walkley, Carl R. Soneji, Shamit Karlsson, Goran Raya, Angel Sankaran, Vijay G. Flygare, Johan TI Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion SO CELL REPORTS LA English DT Article ID PRIMITIVE ERYTHROPOIESIS; BETA-GLOBIN; ERYTHROID-DIFFERENTIATION; MOUSE FIBROBLASTS; GENE-EXPRESSION; STEM-CELLS; INDUCTION; VISUALIZATION; PROGENITORS; GENERATION AB Erythroid cell commitment and differentiation proceed through activation of a lineage-restricted transcriptional network orchestrated by a group of well characterized genes. However, the minimal set of factors necessary for instructing red blood cell (RBC) development remains undefined. We employed a screen for transcription factors allowing direct lineage reprograming from fibroblasts to induced erythroid progenitors/precursors (iEPs). We show that Gata1, Tal1, Lmo2, and c-Myc (GTLM) can rapidly convert murine and human fibroblasts directly to iEPs. The transcriptional signature of murine iEPs resembled mainly that of primitive erythroid progenitors in the yolk sac, whereas addition of Klf1 or Myb to the GTLM cocktail resulted in iEPs with a more adult-type globin expression pattern. Our results demonstrate that direct lineage conversion is a suitable platform for defining and studying the core factors inducing the different waves of erythroid development. C1 [Capellera-Garcia, Sandra; Dhulipala, Kishori; Siva, Kavitha; Singbrant, Sofie; Flygare, Johan] Lund Univ, Dept Mol Med & Gene Therapy, Lund Stem Cell Ctr, S-22184 Lund, Sweden. [Pulecio, Julian; Raya, Angel] Ctr Regenerat Med Barcelona, Barcelona Biomed Res Pk,Doctor Aiguader 88, Barcelona 08003, Spain. [Rayon-Estrada, Violeta] Rockefeller Univ, New York, NY 10065 USA. [Sommarin, Mikael N. E.; Soneji, Shamit; Karlsson, Goran] Lund Univ, Div Mol Hematol, Lund Stem Cell Ctr, BMC B12, S-22184 Lund, Sweden. [Walkley, Carl R.] Univ Melbourne, St Vincents Hosp, St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. [Walkley, Carl R.] Univ Melbourne, St Vincents Hosp, Dept Med, Fitzroy, Vic 3065, Australia. [Raya, Angel] Catalan Inst Res & Adv Studies, Barcelona 08010, Spain. [Raya, Angel] Biomed Res Networking Ctr Bioengn Biomat & Nanome, Madrid 28029, Spain. [Sankaran, Vijay G.] Harvard Univ, Sch Med, Div Hematol Oncol, Boston Childrens Hosp, Boston, MA 02115 USA. [Sankaran, Vijay G.] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Sankaran, Vijay G.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA 02142 USA. RP Flygare, J (reprint author), Lund Univ, Dept Mol Med & Gene Therapy, Lund Stem Cell Ctr, S-22184 Lund, Sweden. EM johan.flygare@med.lu.se OI Walkley, Carl/0000-0002-4784-9031; Raya, Angel/0000-0003-2189-9775 FU Ragnar Soderberg Foundation; Swedish Research Council; Stiftelsen Olle Engkvist Byggmastare; Swedish Foundation for Strategic Research; Ake Wiberg's Foundation; Marie Curie integration grant; MINECO [SAF2012-33526]; ISCIII - FEDER [RETICS RD12/0019/0019, RD12/0019/0034]; Fundacio Marato de TV3 [121430]; AGAUR [2014-SGR-1460, 2014-SGR-1570]; Juan de la Cierva postdoctoral fellowship [JCI-2012-15293] FX We thank Evelyn Wang and Gregory Hyde (Whitehead Institute, Cambridge, MA) for cloning and Harvey Lodish (Whitehead Institute) for providing many of the plasmids used for generating the retroviral library. We thank Jacob Ulirsch (Broad Institute of MIT and Harvard) for early contributions to the global gene expression analysis. We thank Roger Ronn (Department of Molecular Medicine and Gene Therapy) for input on the manuscript and Zhi Ma (Lund Stem Cell Center) for flow cytometry assistance. This work was supported by the Ragnar Soderberg Foundation (to J.F.); the Swedish Research Council (to J.F.); Stiftelsen Olle Engkvist Byggmastare (to J.F.); the Swedish Foundation for Strategic Research (to J.F.); Ake Wiberg's Foundation (to J.F.); a Marie Curie integration grant (to J.F.); and grants from MINECO (SAF2012-33526) (to A.R.), ISCIII - FEDER (RETICS RD12/0019/0019, RD12/0019/0034) (to A.R.), Fundacio Marato de TV3 (121430) (to A.R.), and AGAUR (2014-SGR-1460, 2014-SGR-1570) (to A.R.). J.P. was partially supported by a Juan de la Cierva postdoctoral fellowship (JCI-2012-15293). NR 45 TC 5 Z9 5 U1 0 U2 2 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 JUN 14 PY 2016 VL 15 IS 11 BP 2550 EP 2562 DI 10.1016/j.celrep.2016.05.027 PG 13 WC Cell Biology SC Cell Biology GA DO4TG UT WOS:000377776400022 PM 27264182 ER PT J AU Maron, BA AF Maron, Bradley A. TI Independence Day Separating Right Ventricular Function From Pulmonary Arterial Hypertension in Systemic Sclerosis SO CIRCULATION LA English DT Editorial Material DE Editorials; pulmonary hypertension; right ventricle; scleroderma ID SCLERODERMA; PRESSURE; SURVIVAL; THERAPY C1 [Maron, Bradley A.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. [Maron, Bradley A.] Harvard Univ, Sch Med, Boston, MA USA. [Maron, Bradley A.] Boston VA Healthcare Syst, Dept Cardiol, Boston, MA USA. RP Maron, BA (reprint author), 77 Ave Louis Pasteur,NRB Room 0630-N, Boston, MA 02115 USA. EM bmaron@partners.org FU American Heart Association-American Stroke Association; NHLBI NIH HHS [K08 HL111207] NR 20 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JUN 14 PY 2016 VL 133 IS 24 BP 2345 EP 2347 DI 10.1161/CIRCULATIONAHA.116.023237 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DO8PI UT WOS:000378045100007 PM 27169738 ER PT J AU Wang, CCL Hess, CN Hiatt, WR Goldfine, AB AF Wang, Cecilia C. Low Hess, Connie N. Hiatt, William R. Goldfine, Allison B. TI Clinical Update: Cardiovascular Disease in Diabetes Mellitus Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes Mellitus - Mechanisms, Management, and Clinical Considerations SO CIRCULATION LA English DT Review DE cardiovascular diseases; diabetes mellitus; drugs; heart failure; trials ID VASCULAR SMOOTH-MUSCLE; RANDOMIZED CONTROLLED-TRIAL; CORONARY-ARTERY-DISEASE; C-REACTIVE PROTEIN; PLACEBO-CONTROLLED TRIAL; BLOOD-PRESSURE CONTROL; NF-KAPPA-B; HIGH-DENSITY-LIPOPROTEIN; VENTRICULAR SYSTOLIC DYSFUNCTION; PRESERVED EJECTION FRACTION AB Cardiovascular disease remains the principal cause of death and disability among patients with diabetes mellitus. Diabetes mellitus exacerbates mechanisms underlying atherosclerosis and heart failure. Unfortunately, these mechanisms are not adequately modulated by therapeutic strategies focusing solely on optimal glycemic control with currently available drugs or approaches. In the setting of multifactorial risk reduction with statins and other lipid-lowering agents, antihypertensive therapies, and antihyperglycemic treatment strategies, cardiovascular complication rates are falling, yet remain higher for patients with diabetes mellitus than for those without. This review considers the mechanisms, history, controversies, new pharmacological agents, and recent evidence for current guidelines for cardiovascular management in the patient with diabetes mellitus to support evidence-based care in the patient with diabetes mellitus and heart disease outside of the acute care setting. C1 [Wang, Cecilia C. Low] Univ Colorado, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Aurora, CO USA. [Wang, Cecilia C. Low; Hess, Connie N.; Hiatt, William R.] CPC Clin Res, Aurora, CO USA. [Hess, Connie N.; Hiatt, William R.] Univ Colorado, Sch Med, Dept Med, Div Cardiol, Aurora, CO USA. [Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Goldfine, Allison B.] Harvard Univ, Sch Med, 1 Joslin Pl, Boston, MA 02215 USA. RP Goldfine, AB (reprint author), Harvard Univ, Sch Med, 1 Joslin Pl, Boston, MA 02215 USA.; Goldfine, AB (reprint author), Joslin Diabet Ctr, Sect Clin Res, 1 Joslin Pl, Boston, MA 02215 USA. EM allison.goldfine@joslin.harvard.edu FU AstraZeneca; Bayer; GSK; Janssen; National Institutes of Health; American Diabetes Association; Cleveland Clinic - Ethicon; Covidien FX Dr Hiatt receives grant support from the AstraZeneca, Bayer, GSK, and Janssen, and he serves as a consultant for Kowa. Dr Goldfine receives grant support from the National Institutes of Health, the American Diabetes Association, and Cleveland Clinic sponsored by Ethicon and Covidien. She receives supplies from Amneal Pharmaceuticals, Novo Nordisk, Lifescan, a Division of Johnson and Johnson, and Nestle, Inc. She is a site investigator for Xoma and Diasome, and institutional consultant to Kowa. The other authors report no conflicts. NR 504 TC 6 Z9 6 U1 14 U2 24 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JUN 14 PY 2016 VL 133 IS 24 BP 2459 EP 2502 DI 10.1161/CIRCULATIONAHA.116.022194 PG 44 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DO8PI UT WOS:000378045100018 ER PT J AU Isselbacher, EM Cardenas, CLL Lindsay, ME AF Isselbacher, Eric M. Cardenas, Christian Lacks Lino Lindsay, Mark E. TI Hereditary Influence in Thoracic Aortic Aneurysm and Dissection SO CIRCULATION LA English DT Article DE aorta; aortic disease; Marfan syndrome ID SMOOTH-MUSCLE-CELLS; TRANSFORMING-GROWTH-FACTOR; EHLERS-DANLOS-SYNDROME; SHPRINTZEN-GOLDBERG SYNDROME; OF-FUNCTION MUTATIONS; FACTOR RECEPTOR-BETA; MARFAN-SYNDROME; TGF-BETA; ANGIOTENSIN-II; INTERNATIONAL REGISTRY AB Thoracic aortic aneurysm is a potentially life-threatening condition in that it places patients at risk for aortic dissection or rupture. However, our modern understanding of the pathogenesis of thoracic aortic aneurysm is quite limited. A genetic predisposition to thoracic aortic aneurysm has been established, and gene discovery in affected families has identified several major categories of gene alterations. The first involves mutations in genes encoding various components of the transforming growth factor beta (TGF-beta) signaling cascade (FBN1, TGFBR1, TGFBR2, TGFB2, TGFB3, SMAD2, SMAD3 and SKI), and these conditions are known collectively as the TGF-beta vasculopathies. The second set of genes encode components of the smooth muscle contractile apparatus (ACTA2, MYH11, MYLK, and PRKG1), a group called the smooth muscle contraction vasculopathies. Mechanistic hypotheses based on these discoveries have shaped rational therapies, some of which are under clinical evaluation. This review discusses published data on genes involved in thoracic aortic aneurysm and attempts to explain divergent hypotheses of aneurysm origin. C1 [Isselbacher, Eric M.; Cardenas, Christian Lacks Lino; Lindsay, Mark E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Thorac Aort Ctr, Boston, MA USA. [Lindsay, Mark E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Genet Program, Boston, MA USA. [Cardenas, Christian Lacks Lino; Lindsay, Mark E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. [Isselbacher, Eric M.; Cardenas, Christian Lacks Lino; Lindsay, Mark E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Lindsay, Mark E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Lindsay, Mark E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Cardiol Div,Dept Pediat, Boston, MA USA. RP Lindsay, ME (reprint author), Harvard Univ, Sch Med, Med, Richard B Simches Res Bldg,Room 3224, Boston, MA 02114 USA. EM Lindsay.Mark@mgh.harvard.edu OI lino cardenas, christian/0000-0001-5491-4375 FU National Institutes of Health [HL130113]; American Heart Association [14GRNT18420018]; Toomey Fund for Aortic Dissection Research; Fredman Fellowship FX M.E.L. is supported by a grant from the National Institutes of Health (HL130113), a Grant-in-Aid from the American Heart Association (14GRNT18420018), and by the Toomey Fund for Aortic Dissection Research and the Fredman Fellowship. NR 116 TC 3 Z9 4 U1 7 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JUN 14 PY 2016 VL 133 IS 24 BP 2516 EP 2528 DI 10.1161/CIRCULATIONAHA.116.009762 PG 13 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DO8PI UT WOS:000378045100020 PM 27297344 ER PT J AU Kressin, NR Chapman, SE Magnani, JW AF Kressin, Nancy R. Chapman, Sheila E. Magnani, Jared W. TI A Tale of Two Patients Patient-Centered Approaches to Adherence as a Gateway to Reducing Disparities SO CIRCULATION LA English DT Article DE adherence; disparities, healthcare; ethnicity; patient-centered care; social determinants of health; socioeconomic status; treatment ID MEDICATION ADHERENCE; HEALTH-CARE; RACIAL DISPARITIES; ETHNIC DISPARITIES; HEART-ASSOCIATION; NATIONAL-HEALTH; UNITED-STATES; RISK-FACTORS; HYPERTENSION; MORTALITY AB The disparate effects of social determinants of health on cardiovascular health status and health care have been extensively documented by epidemiology. Yet, very little attention has been paid to how understanding and addressing social determinants of health might improve the quality of clinical interactions, especially by improving patients' adherence to recommended therapies. We present a case and suggested approach to illustrate how cardiovascular clinicians can use patient-centered approaches to identify and address social determinants of health barriers to adherence and reduce the impact of unconscious clinician biases. We propose that cardiovascular clinicians (1) recognize that patients may have different belief systems about illnesses' cause and treatment, which may influence their actions, and not assume they share one's experiences or explanatory model; (2) Endeavor to understand the individual patient before you; (3) based on that understanding, tailor your approach to that individual. We suggest a previously-developed mnemonic for an approach to RESPECT the patient: First, show Respect; then elicit patients' understandings of their illness by asking about their Explanatory model. Ask about the patient's Social context, share Power in the interaction, show Empathy, ask about Concerns or fears, and work to develop Trust by building the relationship over time. We provide additional clinical resources to support these efforts, including lay descriptions of cardiovascular conditions, challenges to adherence, and suggested strategies to address them. C1 [Kressin, Nancy R.] VA Boston Healthcare Syst, Jamaica Plain, MA USA. [Kressin, Nancy R.; Chapman, Sheila E.] Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Kressin, Nancy R.; Chapman, Sheila E.] Boston Med Ctr, Boston, MA USA. [Magnani, Jared W.] Univ Pittsburgh, UPMC Heart & Vasc Inst, Div Cardiol, Dept Med, Pittsburgh, PA 15260 USA. RP Kressin, NR (reprint author), Gen Internal Med Sect, 801 Massachusetts Ave, Boston, MA 02118 USA. EM Nkressin@bu.edu FU Department of Veterans Affairs, Health Services Research & Development Service [RCS 02-066-1]; National Institutes of Health [1U01HL105342-01]; Doris Duke Charitable Foundation [2015084] FX Dr Kressin was supported in part by a Senior Research Career Scientist award from the Department of Veterans Affairs, Health Services Research & Development Service (RCS 02-066-1) and a National Institutes of Health grant (1U01HL105342-01, NR Kressin, PI). Dr Magnani is supported by Grant 2015084 from the Doris Duke Charitable Foundation. NR 74 TC 0 Z9 0 U1 5 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JUN 14 PY 2016 VL 133 IS 24 BP 2583 EP 2592 DI 10.1161/CIRCULATIONAHA.116.015361 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DO8PI UT WOS:000378045100028 PM 27297350 ER PT J AU Azadi, M Nia, HT Gauci, SJ Ortiz, C Fosang, AJ Grodzinsky, AJ AF Azadi, Mojtaba Nia, Hadi Tavakoli Gauci, Stephanie J. Ortiz, Christine Fosang, Amanda J. Grodzinsky, Alan J. TI Wide bandwidth nanomechanical assessment of murine cartilage reveals protection of aggrecan knock-in mice from joint-overuse SO JOURNAL OF BIOMECHANICS LA English DT Article ID DYNAMIC-MECHANICAL PROPERTIES; ATOMIC-FORCE MICROSCOPY; AFM-BASED RHEOLOGY; ARTICULAR-CARTILAGE; MOUSE MODELS; ANIMAL-MODEL; OSTEOARTHRITIS; COMPRESSION; NANOSCALE AB Aggrecan loss in human and animal cartilage precedes clinical symptoms of osteoarthritis, suggesting that aggrecan loss is an initiating step in cartilage pathology. Characterizing early stages of cartilage degeneration caused by aging and overuse is important in the search for therapeutics. In this study, atomic force microscopy (AFM)-based force-displacement micromechanics, AFM-based wide bandwidth nanomechanics (nanodynamic), and histologic assessments were used to study changes in distal femur cartilage of wildtype mice and mice in which the aggrecan interglobular domain was mutated to make the cartilage aggrecanase-resistant. Half the animals were subjected to voluntary running-wheel exercise of varying durations. Wildtype mice at three selected age groups were compared. While histological assessment was not sensitive enough to capture any statistically significant changes in these relatively young populations of mice, micromechanical assessment captured changes in the quasi-equilibrium structural-elastic behavior of the cartilage matrix. Additionally, nanodynamic assessment captured changes in the fluid-solid poroelastic behavior and the high frequency stiffness of the tissue, which proved to be the most sensitive assessment of changes in cartilage associated with aging and joint overuse. In wildtype mice, aging caused softening of the cartilage tissue at the microscale and at the nanoscale. Softening with increased animal age was found at high loading rates (frequencies), suggesting an increase in hydraulic permeability, with implications for loss of function pertinent to running and impact-injury. Running caused substantial changes in fluid-solid interactions in aggrecanase-resistant mice, suggestive of tissue degradation. However, higher nanodynamic stiffness magnitude and lower hydraulic permeability was observed in running aggrecanase-resistant mice compared to running wildtype controls at the same age, thereby suggesting protection from joint-overuse. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Azadi, Mojtaba] San Francisco State Univ, Coll Sci & Engn, Sch Engn, San Francisco, CA 94132 USA. [Ortiz, Christine] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. [Nia, Hadi Tavakoli] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02139 USA. [Gauci, Stephanie J.; Fosang, Amanda J.] Univ Melbourne, Dept Pediat, Parkville, Vic 3052, Australia. [Gauci, Stephanie J.; Fosang, Amanda J.] Murdoch Childrens Res Inst, Parkville, Vic, Australia. [Azadi, Mojtaba; Grodzinsky, Alan J.] MIT, Ctr Biomed Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Azadi, Mojtaba; Grodzinsky, Alan J.] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Grodzinsky, Alan J.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. RP Azadi, M (reprint author), San Francisco State Univ, Coll Sci & Engn, Sch Engn, San Francisco, CA 94132 USA.; Azadi, M (reprint author), MIT, Ctr Biomed Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Azadi, M (reprint author), MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM Azadi@sfsu.edu OI Fosang, Amanda /0000-0002-5523-5427 FU Arthritis Australia; U.S. National Institute of Health (NIH) [AR060331]; National Science Foundation [DEB-0908187] FX The authors are grateful for the support of the Arthritis Australia and the U.S. National Institute of Health (NIH Grant AR060331) and National Science Foundation funding (DEB-0908187). Use of equipment in the Institute for Soldier Nano technologies and Center for Materials Science and Engineering at MIT is gratefully acknowledged. NR 30 TC 1 Z9 1 U1 5 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 EI 1873-2380 J9 J BIOMECH JI J. Biomech. PD JUN 14 PY 2016 VL 49 IS 9 BP 1634 EP 1640 DI 10.1016/j.jbiomech.2016.03.055 PG 7 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA DO4DE UT WOS:000377731200030 PM 27086115 ER PT J AU Dimitriou, D Tsai, TY Park, KK Hosseini, A Kwon, YM Rubash, HE Li, GA AF Dimitriou, Dimitris Tsai, Tsung-Yuan Park, Kwan Kyu Hosseini, Ali Kwon, Young-Min Rubash, Harry E. Li, Guoan TI Weight-bearing condyle motion of the knee before and after cruciate-retaining TKA: In-vivo surgical transepicondylar axis and geometric center axis analyses SO JOURNAL OF BIOMECHANICS LA English DT Article DE In-vivo kinematics; Soft tissue balancing; Gap balance; Geometric center axis (GCA); Surgical transepicondylar axis (sTEA); Total knee arthroplasty (TKA) ID JOINT LINE-POSITION; LIGAMENT DEFICIENCY; FEMORAL COMPONENT; STANCE PHASE; ARTHROPLASTY; FLEXION; KINEMATICS; GAP; ANTERIOR; REPLACEMENT AB An equal knee joint height during flexion and extension is of critical importance in optimizing soft-tissue balancing following total knee arthroplasty (TKA). However, there is a paucity of data regarding the in-vivo knee joint height behavior. This study evaluated in-vivo heights and anterior-posterior (AP) translations of the medial and lateral femoral condyles before and after a cruciate-retaining (CR)-TKA using two flexion axes: surgical transepicondylar axis (sTEA) and geometric center axis (GCA). Eleven osteoarthritis (OA) knee patients were studied during a weight-bearing single leg lunge, using a validated dual fluoroscopic imaging system (DFIS) based tracking technique. Eight healthy subjects were recruited as controls. The results demonstrated that following TKA, the medial and lateral femoral condyle heights were not equal at mid-flexion (15-45 degrees, medial condyle lower then lateral by 2.4 mm at least, p < 0.01), although the knees were well-balanced at 0 degrees and 90 degrees. While the femoral condyle heights increased from the pre-operative values (> 2 mm increase on average, p < 0.05), they were similar to the intact knees except that the medial sTEA was lower than the intact medial condyle between 0 and 90. At deep flexion (> 90 degrees), both condyles were significantly higher ( > 2 mm, p < 0.01) than the healthy knees. Anterior femoral translation of the TKA knee was more pronounce at mid-flexion, whereas limited posterior translation was found at deep flexion. These data suggest that a well-balanced knee intra-operatively might not necessarily result in mid-flexion and deep flexion balance during functional weight-bearing motion, implying mid-flexion instability and deep flexion tightness of the knee. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Dimitriou, Dimitris; Tsai, Tsung-Yuan; Park, Kwan Kyu; Hosseini, Ali; Kwon, Young-Min; Rubash, Harry E.; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02114 USA. [Park, Kwan Kyu] Yonsei Univ, Coll Med, Dept Orthoped Surg, Seoul 120749, South Korea. RP Li, GA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA.; Li, GA (reprint author), Harvard Univ, Sch Med, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@mgh.Harvard.edu OI Dimitriou, Dimitris/0000-0002-9558-7080 NR 35 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 EI 1873-2380 J9 J BIOMECH JI J. Biomech. PD JUN 14 PY 2016 VL 49 IS 9 BP 1891 EP 1898 DI 10.1016/j.jbiomech.2016.04.033 PG 8 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA DO4DE UT WOS:000377731200065 PM 27166758 ER PT J AU Nelson, CM Dewald, JPA Murray, WM AF Nelson, Christa M. Dewald, Julius P. A. Murray, Wendy M. TI In vivo measurements of biceps brachii and triceps brachii fascicle lengths using extended field-of-view ultrasound SO JOURNAL OF BIOMECHANICS LA English DT Article DE Muscle architecture; Fascicle length; Ultrasonography; Upper extremity ID MUSCLE ARCHITECTURE; SKELETAL-MUSCLE; ULTRASONOGRAPHY; RELIABILITY; VALIDITY; US AB Muscle fascicle lengths are commonly measured in vivo using static 2D ultrasound. However, static ultrasound is best suited for muscles with shorter, pennate fascicles, in which entire fascicles can be viewed in one static image. An informal review of data from cadaver dissections suggests that over 60% of muscles in the upper and lower limbs have optimal lengths longer than the field-of-view of standard ultrasound transducers. Extended field-of-view ultrasound (EFOV) has been validated for measurement of fascicle lengths, but has yet to be implemented in the upper extremity in humans. In this study, EFOV ultrasound was used to measure the lengths of fascicles sampled from the anterior portion of the biceps brachii (long head) and the distal half of the triceps brachii (lateral head). Data were collected from both limbs of eleven healthy subjects in three elbow postures under passive conditions. Image analysis was completed via Image J. Fascicle length measurements were highly reliable, with intra-class correlations ranging from .92 to .95 for biceps and .81-.92 for triceps (p < .001). Systematic, significant differences in measured lengths, consistent with muscle function, were observed between elbow positions. In vivo measurements for both muscles in this study were within the range of cadaver data. This work establishes the feasibility and reliability of EFOV ultrasound for measurement of the long fascicles of muscles in the upper limb. Published by Elsevier Ltd. C1 [Nelson, Christa M.; Dewald, Julius P. A.; Murray, Wendy M.] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA. [Dewald, Julius P. A.; Murray, Wendy M.] Northwestern Univ, Dept Phys Med & Rehabil, Feinberg Sch Med, Chicago, IL 60611 USA. [Nelson, Christa M.; Dewald, Julius P. A.; Murray, Wendy M.] Northwestern Univ, Dept Phys Therapy & Human Movement Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [Murray, Wendy M.] Rehabil Inst Chicago, Sensory Motor Performance Program, 345 E Super St, Chicago, IL 60611 USA. [Murray, Wendy M.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. RP Murray, WM (reprint author), Rehabil Inst Chicago, Sensory Motor Performance Program, 345 E Super St, Chicago, IL 60611 USA. EM w-murray@northwestern.edu RI Murray, Wendy/D-1520-2009; Murray, Wendy/B-7629-2009 OI Murray, Wendy/0000-0002-7547-621X; FU American Heart Association [14PRE20240022]; Northwestern University; NIH-NIBIB [T32EB009406]; NIH R01 [1R01HD084009-01A1]; Northwestern University Department of Physical Therapy and Human Movement Sciences; Searle Funds of the Chicago Community Trust FX We would like to acknowledge funding from the American Heart Association (#14PRE20240022), Northwestern University terminal year fellowship, NIH-NIBIB (#T32EB009406), NIH R01 to Drs. Dewald and Murray (#1R01HD084009-01A1), Northwestern University Department of Physical Therapy and Human Movement Sciences, and the Searle Funds of the Chicago Community Trust. We would also like to acknowledge Ana Maria Acosta for her help with development of the experimental GUI, and Paul Krueger and Vikram Darbhe for their assistance during experiments. NR 26 TC 0 Z9 0 U1 5 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 EI 1873-2380 J9 J BIOMECH JI J. Biomech. PD JUN 14 PY 2016 VL 49 IS 9 BP 1948 EP 1952 DI 10.1016/j.jbiomech.2016.03.040 PG 5 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA DO4DE UT WOS:000377731200073 PM 27083062 ER PT J AU Lagerweij, T Hiddingh, L Biesmans, D Crommentuijn, MHW Cloos, J Li, XN Kogiso, M Tannous, BA Vandertop, WP Noske, DP Kaspers, GJL Wurdinger, T Hulleman, E AF Lagerweij, Tonny Hiddingh, Lotte Biesmans, Dennis Crommentuijn, Matheus H. W. Cloos, Jacqueline Li, Xiao-Nan Kogiso, Mari Tannous, Bakhos A. Vandertop, W. Peter Noske, David P. Kaspers, Gertjan J. L. Wurdinger, Tom Hulleman, Esther TI A chemical screen for medulloblastoma identifies quercetin as a putative radiosensitizer SO ONCOTARGET LA English DT Article DE medulloblastoma; quercetin; radiosensitizer; small molecule; screen ID NERVOUS-SYSTEM TUMORS; IN-VIVO; PEDIATRIC MEDULLOBLASTOMA; FLAVONOID QUERCETIN; BRAIN IRRADIATION; YOUNG-CHILDREN; POTENTIAL ROLE; GLIOMA-CELLS; CANCER CELLS; WHOLE-BRAIN AB Treatment of medulloblastoma in children fails in approximately 30% of patients, and is often accompanied by severe late sequelae. Therefore, more effective drugs are needed that spare normal tissue and diminish long-term side effects. Since radiotherapy plays a pivotal role in the treatment of medulloblastoma, we set out to identify novel drugs that could potentiate the effect of ionizing radiation. Thereto, a small molecule library, consisting of 960 chemical compounds, was screened for its ability to sensitize towards irradiation. This small molecule screen identified the flavonoid quercetin as a novel radiosensitizer for the medulloblastoma cell lines DAOY, D283-med, and, to a lesser extent, D458-med at low micromolar concentrations and irradiation doses used in fractionated radiation schemes. Quercetin did not affect the proliferation of neural precursor cells or normal human fibroblasts. Importantly, in vivo experiments confirmed the radiosensitizing properties of quercetin. Administration of this flavonoid at the time of irradiation significantly prolonged survival in orthotopically xenografted mice. Together, these findings indicate that quercetin is a potent radiosensitizer for medulloblastoma cells that may be a promising lead for the treatment of medulloblastoma in patients. C1 [Lagerweij, Tonny; Hiddingh, Lotte; Biesmans, Dennis; Cloos, Jacqueline; Kaspers, Gertjan J. L.; Hulleman, Esther] Vrije Univ Amsterdam Med Ctr, Dept Pediat Oncol Hematol, Amsterdam, Netherlands. [Lagerweij, Tonny; Hiddingh, Lotte; Vandertop, W. Peter; Noske, David P.; Wurdinger, Tom; Hulleman, Esther] Vrije Univ Amsterdam Med Ctr, Dept Neurosurg, Amsterdam, Netherlands. [Lagerweij, Tonny; Hiddingh, Lotte; Biesmans, Dennis; Crommentuijn, Matheus H. W.; Noske, David P.; Wurdinger, Tom; Hulleman, Esther] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Neurooncol, Res Grp, Amsterdam, Netherlands. [Li, Xiao-Nan; Kogiso, Mari] Baylor Coll Med, Texas Childrens Canc Ctr, Dept Pediat, Houston, TX 77030 USA. [Tannous, Bakhos A.; Wurdinger, Tom] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. [Tannous, Bakhos A.; Wurdinger, Tom] Harvard Univ, Sch Med, Boston, MA USA. RP Hulleman, E (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Pediat Oncol Hematol, Amsterdam, Netherlands.; Hulleman, E (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Neurosurg, Amsterdam, Netherlands.; Hulleman, E (reprint author), Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Neurooncol, Res Grp, Amsterdam, Netherlands. EM e.hulleman@vumc.nl OI Lagerweij, Tonny/0000-0003-1043-7452; Intveld, Linda/0000-0003-0036-734X; Crommentuijn, Matheus/0000-0001-8217-5370 FU Stichting KiKa-Foundation Children Cancer-free FX This study was supported by Stichting KiKa-Foundation Children Cancer-free (EH, TW). NR 63 TC 1 Z9 1 U1 0 U2 1 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JUN 14 PY 2016 VL 7 IS 24 BP 35776 EP 35788 DI 10.18632/oncotarget.7980 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DO4MJ UT WOS:000377756800023 PM 26967057 ER PT J AU Miller, MB Bi, WL Ramkissoon, LA Kang, YJ Abedalthagafi, M Knoff, DS Agarwalla, PK Wen, PY Reardon, DA Alexander, BM Laws, ER Dunn, IF Beroukhim, R Ligon, KL Ramkissoon, SH AF Miller, Michael B. Bi, Wenya Linda Ramkissoon, Lori A. Kang, Yun Jee Abedalthagafi, Malak Knoff, David S. Agarwalla, Pankaj K. Wen, Patrick Y. Reardon, David A. Alexander, Brian M. Laws, Edward R., Jr. Dunn, Ian F. Beroukhim, Rameen Ligon, Keith L. Ramkissoon, Shakti H. TI MAPK activation and HRAS mutation identified in pituitary spindle cell oncocytoma SO ONCOTARGET LA English DT Article DE spindle cell oncocytoma; pituitary; MAPK; HRAS; genomics ID COMPARATIVE GENOMIC HYBRIDIZATION; MULTIPLE ENDOCRINE NEOPLASIA; DNA-SEQUENCING DATA; SOMATIC MUTATIONS; PROSTATE-CANCER; GENE-MUTATIONS; RAS MUTATIONS; H-RAS; ADENOHYPOPHYSIS; ADENOMAS AB Pituitary spindle cell oncocytoma (SCO) is an uncommon primary pituitary neoplasm that presents with mass effect on adjacent neurovascular structures, similar to non-hormone-producing pituitary adenomas. To determine the molecular etiology of SCO, we performed exome sequencing on four SCO cases, with matched normal controls, to assess somatic mutations and copy number alterations. Our analysis revealed a low mutation rate and a copy-neutral profile, consistent with the low-grade nature of this tumor. However, we identified a co-occurring somatic HRAS (p.Q61R) activating point mutation and MEN1 frameshift mutation (p.L117fs) present in a primary and recurrent tumor from one patient. Other SCOs demonstrated mutations in SND1 and FAT1, which are associated with MAPK pathway activation. Immunohistochemistry across the SCO cohort demonstrated robust MAPK activity in all cases (n=4), as evidenced by strong phospho-ERK staining, while phospho-AKT levels suggested only basal levels of PI3K pathway activation. Taken together, this identifies the MAPK signaling pathway as a novel therapeutic target for spindle cell oncocytoma, which may offer a powerful adjunct for aggressive tumors refractory to surgical resection. C1 [Miller, Michael B.; Abedalthagafi, Malak; Ligon, Keith L.; Ramkissoon, Shakti H.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Bi, Wenya Linda; Laws, Edward R., Jr.; Dunn, Ian F.] Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St, Boston, MA 02115 USA. [Bi, Wenya Linda; Agarwalla, Pankaj K.; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Ramkissoon, Lori A.; Kang, Yun Jee; Knoff, David S.; Wen, Patrick Y.; Reardon, David A.; Beroukhim, Rameen; Ligon, Keith L.; Ramkissoon, Shakti H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Agarwalla, Pankaj K.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Alexander, Brian M.] Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. [Alexander, Brian M.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Beroukhim, Rameen; Ligon, Keith L.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Ligon, Keith L.; Ramkissoon, Shakti H.] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. [Bi, Wenya Linda; Wen, Patrick Y.; Reardon, David A.; Alexander, Brian M.; Laws, Edward R., Jr.; Dunn, Ian F.; Beroukhim, Rameen; Ligon, Keith L.; Ramkissoon, Shakti H.] Harvard Univ, Sch Med, Boston, MA USA. RP Ligon, KL; Ramkissoon, SH (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.; Ligon, KL; Ramkissoon, SH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.; Ligon, KL (reprint author), Broad Inst MIT & Harvard, Cambridge, MA USA.; Ligon, KL; Ramkissoon, SH (reprint author), Boston Childrens Hosp, Dept Pathol, Boston, MA USA.; Ligon, KL; Ramkissoon, SH (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM keith_ligon@dfci.harvard.edu; sramkissoon@partners.org OI Knoff, David/0000-0001-6233-2893 FU NINDS [K08NS087118] FX This work is supported by NINDS K08NS087118 (SHR) award. NR 55 TC 1 Z9 1 U1 0 U2 0 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JUN 14 PY 2016 VL 7 IS 24 BP 37054 EP 37063 DI 10.18632/oncotarget.9244 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DO4MJ UT WOS:000377756800120 PM 27175596 ER PT J AU Lustberg, T Bailey, M Thwaites, DI Miller, A Carolan, M Holloway, L Velazquez, ER Hoebers, F Dekker, A AF Lustberg, Tim Bailey, Michael Thwaites, David I. Miller, Alexis Carolan, Martin Holloway, Lois Velazquez, Emmanuel Rios Hoebers, Frank Dekker, Andre TI Implementation of a rapid learning platform: Predicting 2-year survival in laryngeal carcinoma patients in a clinical setting SO ONCOTARGET LA English DT Article DE larynx; survival prediction; rapid learning; model validation ID SQUAMOUS-CELL CARCINOMA; RADIATION-THERAPY; EXTERNAL VALIDATION; CANCER-PATIENTS; NECK-CANCER; RADIOTHERAPY; TRIALS; CARE; PARTICIPATION; CHEMOTHERAPY AB Background and Purpose To improve quality and personalization of oncology health care, decision aid tools are needed to advise physicians and patients. The aim of this work is to demonstrate the clinical relevance of a survival prediction model as a first step to multi institutional rapid learning and compare this to a clinical trial dataset. Materials and Methods Data extraction and mining tools were used to collect uncurated input parameters from Illawarra Cancer Care Centre's (clinical cohort) oncology information system. Prognosis categories previously established from the Maastricht Radiation Oncology (training cohort) dataset, were applied to the clinical cohort and the radiotherapy only arm of the RTOG-9111 (trial cohort). Results Data mining identified 125 laryngeal carcinoma patients, ending up with 52 patients in the clinical cohort who were eligible to be evaluated by the model to predict 2-year survival and 177 for the trial cohort. The model was able to classify patients and predict survival in the clinical cohort, but for the trial cohort it failed to do so. Conclusions The technical infrastructure and model is able to support the prognosis prediction of laryngeal carcinoma patients in a clinical cohort. The model does not perform well for the highly selective patient population in the trial cohort. C1 [Lustberg, Tim; Hoebers, Frank; Dekker, Andre] Maastricht Univ Med Ctr, GROW Sch Oncol & Dev Biol, Dept Radiat Oncol MAASTRO, Maastricht, Netherlands. [Bailey, Michael; Miller, Alexis; Carolan, Martin] Illawarra Shoalhaven Local Hlth Dist, Illawarra Canc Care Ctr, Wollongong, NSW, Australia. [Bailey, Michael; Miller, Alexis] Univ Wollongong, Ctr Oncol Informat, Wollongong, NSW, Australia. [Thwaites, David I.; Holloway, Lois] Univ Sydney, Sch Phys, Inst Med Phys, Sydney, NSW 2006, Australia. [Bailey, Michael; Carolan, Martin] Illawarra Hlth & Med Res Inst, Wollongong, NSW, Australia. [Bailey, Michael; Carolan, Martin; Holloway, Lois] Univ Wollongong, Ctr Med Radiat Phys, Wollongong, NSW, Australia. [Holloway, Lois] Univ New S Wales, South Western Clin Sch, Sydney, NSW, Australia. [Holloway, Lois] Ingham Inst, Liverpool, Australia. [Holloway, Lois] Liverpool Canc Therapy Ctr, Liverpool, Australia. [Holloway, Lois] Macarthur Canc Therapy Ctr, Liverpool, Australia. [Velazquez, Emmanuel Rios] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RP Lustberg, T (reprint author), Maastricht Univ Med Ctr, GROW Sch Oncol & Dev Biol, Dept Radiat Oncol MAASTRO, Maastricht, Netherlands. EM tim.lustberg@maastro.nl FU Illawarra Cancer Care Centre FX We would like to thank the NRG/RTOG for making the data of the RTOG-91-11 trial available; and the Illawarra Cancer Care Centre for funding Tim Lustberg's visit to Australia, within the NSW/University of Sydney data mining collaborative network project. NR 29 TC 0 Z9 0 U1 1 U2 1 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JUN 14 PY 2016 VL 7 IS 24 BP 37288 EP 37296 DI 10.18632/oncotarget.8755 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DO4MJ UT WOS:000377756800138 PM 27095578 ER PT J AU Li, H Wang, SY Kong, R Ding, WG Lee, FH Parker, Z Kim, E Learn, GH Hahn, P Policicchio, B Brocca-Cofano, E Deleage, C Hao, XP Chuang, GY Gorman, J Gardner, M Lewis, MG Hatziioannou, T Santra, S Apetrei, C Pandrea, I Alam, SM Liao, HX Shen, XY Tomaras, GD Farzan, M Chertova, E Keele, BF Estes, JD Lifson, JD Doms, RW Montefiori, DC Haynes, BF Sodroski, JG Kwong, PD Hahn, BH Shaw, GM AF Li, Hui Wang, Shuyi Kong, Rui Ding, Wenge Lee, Fang-Hua Parker, Zahra Kim, Eunlim Learn, Gerald H. Hahn, Paul Policicchio, Ben Brocca-Cofano, Egidio Deleage, Claire Hao, Xingpei Chuang, Gwo-Yu Gorman, Jason Gardner, Matthew Lewis, Mark G. Hatziioannou, Theodora Santra, Sampa Apetrei, Cristian Pandrea, Ivona Alam, S. Munir Liao, Hua-Xin Shen, Xiaoying Tomaras, Georgia D. Farzan, Michael Chertova, Elena Keele, Brandon F. Estes, Jacob D. Lifson, Jeffrey D. Doms, Robert W. Montefiori, David C. Haynes, Barton F. Sodroski, Joseph G. Kwong, Peter D. Hahn, Beatrice H. Shaw, George M. TI Envelope residue 375 substitutions in simian-human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HIV/AIDS; SHIV; CD4; HIV-1 envelope ID BROADLY NEUTRALIZING ANTIBODIES; GP120 INNER DOMAIN; INFECTIOUS MOLECULAR CLONES; HIV-1 ENVELOPE; IN-VIVO; CONFORMATIONAL TRANSITIONS; QUATERNARY INTERACTIONS; CD4-BOUND CONFORMATION; SUBOPTIMAL NUCLEOTIDES; CHALLENGE STOCKS AB Most simian-human immunodeficiency viruses (SHIVs) bearing envelope (Env) glycoproteins from primary HIV-1 strains fail to infect rhesus macaques (RMs). We hypothesized that inefficient Env binding to rhesus CD4 (rhCD4) limits virus entry and replication and could be enhanced by substituting naturally occurring simian immunodeficiency virus Env residues at position 375, which resides at a critical location in the CD4-binding pocket and is under strong positive evolutionary pressure across the broad spectrum of primate lentiviruses. SHIVs containing primary or transmitted/founder HIV-1 subtype A, B, C, or D Envs with genotypic variants at residue 375 were constructed and analyzed in vitro and in vivo. Bulky hydrophobic or basic amino acids substituted for serine-375 enhanced Env affinity for rhCD4, virus entry into cells bearing rhCD4, and virus replication in primary rhCD4 T cells without appreciably affecting antigenicity or antibody-mediated neutralization sensitivity. Twenty-four RMs inoculated with subtype A, B, C, or D SHIVs all became productively infected with different Env375 variants-S, M, Y, H, W, or F-that were differentially selected in different Env backbones. Notably, SHIVs replicated persistently at titers comparable to HIV-1 in humans and elicited autologous neutralizing antibody responses typical of HIV-1. Seven animals succumbed to AIDS. These findings identify Env-rhCD4 binding as a critical determinant for productive SHIV infection in RMs and validate a novel and generalizable strategy for constructing SHIVs with Env glycoproteins of interest, including those that in humans elicit broadly neutralizing antibodies or bind particular Ig germ-line B-cell receptors. C1 [Li, Hui; Wang, Shuyi; Kong, Rui; Ding, Wenge; Lee, Fang-Hua; Parker, Zahra; Kim, Eunlim; Learn, Gerald H.; Hahn, Paul; Hahn, Beatrice H.; Shaw, George M.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Policicchio, Ben; Brocca-Cofano, Egidio; Apetrei, Cristian; Pandrea, Ivona] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA 15261 USA. [Deleage, Claire; Hao, Xingpei; Chertova, Elena; Keele, Brandon F.; Estes, Jacob D.; Lifson, Jeffrey D.; Kwong, Peter D.] Frederick Natl Lab, Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick, MD 21702 USA. [Chuang, Gwo-Yu; Gorman, Jason] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Gardner, Matthew; Farzan, Michael] Scripps Res Inst, Dept Infect Dis, Jupiter, FL 33458 USA. [Lewis, Mark G.] Bioqual Inc, Rockville, MD 20852 USA. [Hatziioannou, Theodora] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. [Santra, Sampa] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA. [Alam, S. Munir; Liao, Hua-Xin; Shen, Xiaoying; Tomaras, Georgia D.; Montefiori, David C.; Haynes, Barton F.] Duke Univ, Dept Med, Durham, NC 27710 USA. [Doms, Robert W.] Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA. [Sodroski, Joseph G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02215 USA. RP Hahn, BH; Shaw, GM (reprint author), Univ Penn, Dept Med, Philadelphia, PA 19104 USA. EM bhahn@upenn.edu; shawg@upenn.edu FU Bill & Melinda Gates Foundation [OPP37874, OPP1145046]; NIH Grants [AI100645, AI088564, AI094604, AI087383, AI078788, AI045008, HHSN261200800001E] FX We thank C. Xu, T. He, T. Dunsmore, G. H. Richter, K. Raehtz, J. Roser, R. Fast, K. Oswald, R. Shoemaker, J. Bess, and A. Meyer for technical assistance. This project was funded in part by Bill & Melinda Gates Foundation Grants OPP37874 and OPP1145046; and NIH Grants AI100645, AI088564, AI094604, AI087383, AI078788, AI045008, and HHSN261200800001E. NR 117 TC 12 Z9 12 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 14 PY 2016 VL 113 IS 24 BP E3413 EP E3422 DI 10.1073/pnas.1606636113 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DO7FW UT WOS:000377948800015 PM 27247400 ER PT J AU Li, K Laird, AR Price, LR Mckay, DR Blangero, J Glahn, DC Fox, PT AF Li, Karl Laird, Angela R. Price, Larry R. McKay, D. Reese Blangero, John Glahn, David C. Fox, Peter T. TI Progressive Bidirectional Age-Related Changes in Default Mode Network Effective Connectivity across Six Decades SO FRONTIERS IN AGING NEUROSCIENCE LA English DT Article DE default mode network (DMN); structural equation modeling (SEM); meta-analytic connectivity modeling; functional connectivity (FC); normal aging ID STATE FUNCTIONAL CONNECTIVITY; EARLY ALZHEIMERS-DISEASE; CONSCIOUS RESTING STATE; HUMAN BRAIN; STRUCTURAL CONNECTIVITY; MOTION CORRECTION; HEMISPHERIC-ASYMMETRY; AMYLOID DEPOSITION; GRANGER CAUSALITY; OLDER-ADULTS AB The default mode network (DMN) is a set of regions that is tonically engaged during the resting state and exhibits task-related deactivation that is readily reproducible across a wide range of paradigms and modalities. The DMN has been implicated in numerous disorders of cognition and, in particular, in disorders exhibiting age-related cognitive decline. Despite these observations, investigations of the DMN in normal aging are scant. Here, we used blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) acquired during rest to investigate age-related changes in functional connectivity of the DMN in 120 healthy normal volunteers comprising six, 20-subject, decade cohorts (from 20-29 to 70-79). Structural equation modeling (SEM) was used to assess age related changes in inter-regional connectivity within the DMN. SEM was applied both using a previously published, meta-analytically derived, node-and-edge model, and using exploratory modeling searching for connections that optimized model fit improvement. Although the two models were highly similar (only 3 of 13 paths differed), the sample demonstrated significantly better fit with the exploratory model. For this reason, the exploratory model was used to assess age-related changes across the decade cohorts. Progressive, highly significant changes in path weights were found in 8 (of 13) paths: four rising, and four falling (most changes were significant by the third or fourth decade). In all cases, rising paths and falling paths projected in pairs onto the same nodes, suggesting compensatory increases associated with age-related decreases. This study demonstrates that age-related changes in DMN physiology (inter-regional connectivity) are bidirectional, progressive, of early onset and part of normal aging. C1 [Li, Karl; Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Laird, Angela R.] Florida Int Univ, Dept Phys, Miami, FL 33199 USA. [Price, Larry R.] Texas State Univ, Dept Math, San Marcos, TX USA. [Price, Larry R.] Texas State Univ, Coll Educ, San Marcos, TX USA. [McKay, D. Reese; Glahn, David C.] Yale Univ, Dept Psychiat, Sch Med, New Haven, CT 06520 USA. [McKay, D. Reese; Glahn, David C.] Hartford Hosp, Olin Neuropsychiat Res Ctr, Inst Living, Hartford, CT 06115 USA. [Blangero, John] Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Genom Comp Ctr, Edinburg, TX USA. [Fox, Peter T.] South Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX USA. [Fox, Peter T.] Shenzhen Univ, Sch Med, Neuroimaging Lab, Shenzhen, Guangdong, Peoples R China. RP Fox, PT (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA.; Fox, PT (reprint author), South Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX USA.; Fox, PT (reprint author), Shenzhen Univ, Sch Med, Neuroimaging Lab, Shenzhen, Guangdong, Peoples R China. EM fox@uthscsa.edu FU National Institutes of Health [5R01MH074457-09]; NIH [1R01MH078111-01]; Genetics of Brain Structure, and Function study FX This was supported by the National Institutes of Health grant 5R01MH074457-09, Meta-Analysis in Human Brain Mapping. The data was provided for by NIH grant 1R01MH078111-01, the Genetics of Brain Structure, and Function study. Special thanks to Crystal Franklin for help in data pre-processing and Mary Woosley for help in providing demographic information for the data used. NR 112 TC 0 Z9 0 U1 4 U2 6 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1663-4365 J9 FRONT AGING NEUROSCI JI Front. Aging Neurosci. PD JUN 14 PY 2016 VL 8 AR 137 DI 10.3389/fnagi.2016.00137 PG 16 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA DO2AQ UT WOS:000377582100001 PM 27378909 ER PT J AU Bonaca, MP Bhatt, DL Storey, RF Steg, G Cohen, M Kuder, J Goodrich, E Nicolau, JC Parkhomenko, A Lopez-Sendon, J Dellborg, M Dalby, A Spinar, J Aylward, P Corbalan, R Abola, MTB Jensen, EC Held, P Braunwald, E Sabatine, MS AF Bonaca, Marc P. Bhatt, Deepak L. Storey, Robert F. Steg, Gabriel Cohen, Marc Kuder, Julia Goodrich, Erica Nicolau, Jose C. Parkhomenko, Alexander Lopez-Sendon, Jose Dellborg, Mikael Dalby, Anthony Spinar, Jindrich Aylward, Philip Corbalan, Ramon Abola, Maria Teresa B. Jensen, Eva C. Held, Peter Braunwald, Eugene Sabatine, Marc S. TI Ticagrelor for Prevention of Ischemic Events After Myocardial Infarction in Patients With Peripheral Artery Disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE acute limb ischemia; major adverse cardiovascular events; major adverse limb events; peripheral arterial disease; ticagrelor ID INTEGRATED DISCRIMINATION; TRA2-DEGREES-P-TIMI 50; NET RECLASSIFICATION; CHARISMA TRIAL; HEART-ATTACK; RISK; ATHEROTHROMBOSIS; OUTPATIENTS; STROKE; THROMBOLYSIS AB BACKGROUND Peripheral artery disease (PAD) is associated with heightened ischemic and bleeding risk in patients with prior myocardial infarction (MI). OBJECTIVES This study evaluated the efficacy and safety of ticagrelor on major cardiovascular (CV) events and major adverse limb events in patients with PAD and a prior MI. METHODS PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction 54) randomized 21,162 patients with prior MI (1 to 3 years) to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo, all on a background of low-dose aspirin. History of PAD was obtained at baseline. Occurrences of major adverse cardiovascular events (MACE) (defined as CV death, MI, or stroke) and major adverse limb events (MALE) (defined as acute limb ischemia or peripheral revascularization for ischemia) were recorded in follow-up. RESULTS A total of 1,143 patients (5%) had known PAD. In the placebo arm, those with PAD (n = 404) had higher rates of MACE at 3 years than those without (n = 6,663; 19.3% vs. 8.4%; p < 0.001), which persisted after adjusting for baseline differences (adjusted hazard ratio: 1.60; 95% confidence interval: 1.20 to 2.13; p = 0.0013), and higher rates of acute limb ischemia (1.0% vs. 0.1%) and peripheral revascularization procedures (9.15% vs. 0.46%). Whereas the relative risk reduction in MACE with ticagrelor was consistent, regardless of PAD, patients with PAD had a greater absolute risk reduction of 4.1% (number needed to treat: 25) due to their higher absolute risk. The absolute excess of TIMI major bleeding was 0.12% (number needed to harm: 834). The 60-mg dose had particularly favorable outcomes for CV and all-cause mortality. Ticagrelor (pooled doses) reduced the risk of MALE (hazard ratio: 0.65; 95% confidence interval: 0.44 to 0.95; p = 0.026). CONCLUSIONS Among stable patients with prior MI, those with concomitant PAD have heightened ischemic risk. In these patients, ticagrelor reduced MACE, with a large absolute risk reduction, and MALE. (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS-TIMI 54]; NCT01225562) (C) 2016 by the American College of Cardiology Foundation. C1 [Bonaca, Marc P.; Bhatt, Deepak L.; Kuder, Julia; Goodrich, Erica; Braunwald, Eugene; Sabatine, Marc S.] Brigham & Womens Hosp, Heart & Vasc Ctr, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. [Storey, Robert F.] Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, S Yorkshire, England. [Steg, Gabriel] Univ Paris Diderot, French Alliance Cardiovasc Trials, Paris, France. [Cohen, Marc] Icahn Sch Med Mt Sinai, Newark Beth Israel Med Ctr, Div Cardiovasc, New York, NY 10029 USA. [Nicolau, Jose C.] Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, Brazil. [Parkhomenko, Alexander] Ukranian Strazhesko Inst Cardiol, Kiev, Ukraine. [Lopez-Sendon, Jose] Hosp Univ La Paz, Inst Invest La Paz, Madrid, Spain. [Dellborg, Mikael] Univ Gothenburg, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden. [Dalby, Anthony] Life Fourways Hosp, Randburg, South Africa. [Spinar, Jindrich] Univ Hosp, Brno, Czech Republic. [Aylward, Philip] Flinders Med Ctr, Div Med, Cardiac Serv, Bedford Pk, SA, Australia. [Aylward, Philip] Flinders Med Ctr, Div Med, Crit Care Serv, Bedford Pk, SA, Australia. [Corbalan, Ramon] Pontificia Univ Catolica Chile, Div Cardiovasc, Alameda 340, Santiago, Chile. [Abola, Maria Teresa B.] Univ Philippines, Coll Med, Philippine Heart Ctr, Manila, Philippines. [Jensen, Eva C.; Held, Peter] AstraZeneca R&D, Molndal, Sweden. RP Bonaca, MP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM mbonaca@partners.org RI Nicolau, Jose/E-1487-2012 FU AstraZeneca; Merck; Bayer; Roche Diagnostics; Amarin; Bristol-Myers Squibb; Eisai; Ethicon; Forest Laboratories; Ischemix; Medtronic; Pfizer; Roche; Sanofi; Medicines Company; Aspen; PlaqueTec; Correvio; Medscape; Thermo Fisher Scientific; Servier; Janssen; Maquet; malpractice attorneys; Bristol-Myers Squibb/Pfizer; Boehringer Ingelheim; Lilly; Edwards Lifesciences; Amgen; GlaxoSmithKline; Novartis; Lilly/Daiichi-Sankyo; DiscoveryHealth; Daiichi-Sankyo; Population Health Research Institute; Brigham; Women's Hospital from Abbott Laboratories; Critical Diagnostics; Gilead; Intarcia; Poxel; Takeda FX The TIMI Study Group has received significant research grant support from AstraZeneca. Dr. Bonaca has received consulting fees from AstraZeneca, Merck, Bayer, and Roche Diagnostics. Dr. Bhatt has served on the advisory board of Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; has served on the Board of Directors of Boston VA Research Institute, and the Society of Cardiovascular Patient Care; is chair of the American Heart Association Quality Oversight Committee; has served on the data monitoring committees of Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and the Population Health Research Institute; has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), and WebMD (CME steering committees); has served as deputy editor of Clinical Cardiology; has served as vice-chair of the NCDR-ACTION Registry Steering Committee; has served as the chair of the VA CART Research and Publications Committee; has received research funding from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi, and The Medicines Company; has received royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald's Heart Disease); is a site coinvestigator for Biotronik, Boston Scientific, and St. Jude Medical; is a trustee of the American College of Cardiology; and has performed unfunded research for FlowCo, PLx Pharma, and Takeda. Dr. Storey has received grants, personal fees, and travel support from AstraZeneca; and has received personal/consultancy fees from Aspen, PlaqueTec, Correvio, The Medicines Company, Medscape, and Thermo Fisher Scientific. Dr. Steg has received research grants from Merck, Sanofi, and Servier; and has served as a consultant or speaker for Amarin, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, CSL Behring, Daiichi-Sankyo-Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Sanofi, Servier, and The Medicines Company. Dr. Cohen has received grants and personal fees from AstraZeneca during the conduct of the study; outside of this study he has received personal fees from Merck, Janssen, Maquet, malpractice attorneys, Merck, Bristol-Myers Squibb/Pfizer, Boehringer Ingelheim, and Lilly; and has received grants from Janssen and Edwards Lifesciences. Dr. Nicolau has received speaker/consulting honoraria and/or research grant support from Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Merck, Novartis, Pfizer, and Sanofi. Dr. Lopez-Sendon has received research grants from AstraZeneca, Lilly/Daiichi-Sankyo, GlaxoSmithKline, Pfizer, Novartis, and Servier; and has received honoraria from AstraZeneca, Lilly/Daiichi-Sankyo, Merck, and Sanofi. Dr.; Dalby has received personal fees from AstraZeneca during the conduct of the study; and has received personal fees from Aspen, Bayer, Boehringer Ingelheim, DiscoveryHealth, Lilly, Novartis, Pfizer, Sanofi, and Servier outside of the submitted work. Dr. Aylward has received a research grant, has received honoraria for speaking, and served on the advisory board of AstraZeneca. Dr. Abola has received grants and modest personal/speaker fees from and served on the local advisory board for AstraZeneca during the conduct of the study; as an investigator in other ticagrelor trials has received modest personal fees as a member of the advisory board of and as a speaker for Pfizer; has received modest personal fees as speaker for Bayer, Boehringer Ingelheim, and Daiichi-Sankyo; and has received modest investigator fees from Bayer, Boehringer Ingelheim, Daiichi-Sankyo, and Population Health Research Institute. Dr. Jensen is an employee of AstraZeneca. Dr. Held is an employee and stockholder of AstraZeneca. Dr. Braunwald has received institutional grant support from AstraZeneca. Dr. Sabatine has received research grant support through Brigham and Women's Hospital from Abbott Laboratories, Amgen, AstraZeneca, Critical Diagnostics, Daiichi-Sankyo, Eisai, Gilead, GlaxoSmithKline, Intarcia, Merck, Novartis, Poxel, Roche Diagnostics, Sanofi, and Takeda; and has served as a consultant for Alnylam, Amgen, AstraZeneca, Cubist, CVS Caremark, Intarcia, and Merck (all <=$10,000/year). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 19 TC 11 Z9 11 U1 3 U2 9 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 JUN 14 PY 2016 VL 67 IS 23 BP 2719 EP 2728 DI 10.1016/j.jacc.2016.03.524 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DN7RF UT WOS:000377274300003 PM 27046162 ER PT J AU Bhatt, DL Bonaca, MP Bansilal, S Angiolillo, DJ Cohen, M Storey, RF Im, K Murphy, SA Held, P Braunwald, E Sabatine, MS Steg, PG AF Bhatt, Deepak L. Bonaca, Marc P. Bansilal, Sameer Angiolillo, Dominick J. Cohen, Marc Storey, Robert F. Im, Kyungah Murphy, Sabina A. Held, Peter Braunwald, Eugene Sabatine, Marc S. Steg, Ph. Gabriel TI Reduction in Ischemic Events With Ticagrelor in Diabetic Patients With Prior Myocardial Infarction in PEGASUS-TIMI 54 SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE acute coronary syndrome; dual antiplatelet therapy; myocardial infarction; platelets ID ACUTE CORONARY SYNDROMES; OPTIMIZING ANTIPLATELET THERAPY; PLATELET-FUNCTION PROFILES; ARTERY-DISEASE; CARDIOVASCULAR EVENTS; SECONDARY PREVENTION; CLOPIDOGREL; MELLITUS; TRIAL; INHIBITION AB BACKGROUND Patients with diabetes appear to be at elevated risk of atherothrombotic events. OBJECTIVES The purpose of this study was to determine the effect of antiplatelet therapy with ticagrelor on recurrent ischemic events in patients with diabetes and prior myocardial infarction (MI). METHODS We examined the subgroups of patients with diabetes (n = 6,806) and without diabetes (n = 14,355) from PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction 54), in which 21,162 patients with a history of MI 1 to 3 years prior and with additional risk factors were randomized to ticagrelor (90 or 60 mg twice daily) or placebo. Patients were followed for a median of 33 months. The primary efficacy endpoint was major adverse cardiovascular events (MACE) (cardiovascular death, MI, stroke) and the primary safety endpoint was TIMI (Thrombolysis In Myocardial Infarction) major bleeding. RESULTS The relative risk reduction in MACE with ticagrelor was consistent for the pooled doses versus placebo in patients with diabetes (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.72 to 0.99; p = 0.035) and without diabetes (HR: 0.84; 95% CI: 0.74 to 0.96; p = 0.013; p interaction = 0.99). As patients with diabetes were at higher risk of MACE, the absolute risk reduction tended to be greater in patients with versus without diabetes (1.5% vs. 1.1%, with corresponding 3-year number needed to treat of 67 vs. 91). In patients with diabetes requiring pharmacological therapy (n = 5,960), the absolute risk reduction was 1.9% with a 3-year number needed to treat of 53. Additionally, in patients with diabetes, ticagrelor reduced cardiovascular death by 22% and coronary heart disease death by 34%. Similar to patients without diabetes, there was increased TIMI major bleeding in patients with diabetes (HR: 2.56; 95% CI: 1.52 to 4.33; p = 0.0004). CONCLUSIONS In patients with diabetes with prior MI, adding ticagrelor to aspirin significantly reduces the risk of recurrent ischemic events, including cardiovascular and coronary heart disease death. (C) 2016 by the American College of Cardiology Foundation. C1 [Bhatt, Deepak L.; Bonaca, Marc P.; Im, Kyungah; Murphy, Sabina A.; Braunwald, Eugene; Sabatine, Marc S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Heart & Vasc Ctr, Boston, MA 02115 USA. [Bansilal, Sameer] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Angiolillo, Dominick J.] Univ Florida, Jacksonville, FL USA. [Cohen, Marc] Rutgers New Jersey Med Sch, Newark Beth Israel Med Ctr, Div Cardiovasc, Newark, NJ USA. [Storey, Robert F.] Univ Sheffield, Sheffield, S Yorkshire, England. [Held, Peter] AstraZeneca R&D, Molndal, Sweden. [Steg, Ph. Gabriel] Univ Paris Diderot, Sorbonne Paris Cite, Hop Bichat, AP HP,Dept Hospitalouniv Fibrosis,Inflammat,REmod, Paris, France. [Steg, Ph. Gabriel] French Alliance Cardiovasc Clin Trials, INSERM, U1148, Paris, France. RP Bhatt, DL (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA. EM dlbhattmd@post.harvard.edu FU AstraZeneca; Amarin; Bristol-Myers Squibb; Eisai; Ethicon; Forest Laboratories; Ischemix; Medtronic; Pfizer; Roche; Sanofi; Medicines Company; Merck; Bayer; Roche Diagnostics; Eli Lilly; Daiichi-Sankyo; Abbott Vascular; PLx Pharma; GlaxoSmithKline; Janssen Pharmaceuticals, Inc.; Osprey Medical, Inc.; Novartis; CSL Behring; Gilead; Aspen; Correvio; PlaqueTec; Thermo Fisher Scientific; Brigham and Women's Hospital from AstraZeneca; Brigham and Women's Hospital from Abbott Laboratories; Amgen; Critical Diagnostics; Intarcia; Poxel; Takeda; Alnylam; CVS Caremark; Servier; Boehringer Ingelheim; Lilly; Janssen; Regeneron FX PEGASUS-TIMI 54 was funded by AstraZeneca. The TIMI Study Group has received significant research grant support from AstraZeneca. Dr. Bhatt has served on the advisory board of Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; has served on the Board of Directors of Boston VA Research Institute, and the Society of Cardiovascular Patient Care; is chair of the American Heart Association Quality Oversight Committee; has served on the data monitoring committees of Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and the Population Health Research Institute; has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), and WebMD (CME steering committees); has served as deputy editor of Clinical Cardiology; has served as vice-chair of the NCDR-ACTION Registry Steering Committee; has served as the chair of the VA CART Research and Publications Committee; has received research funding from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi, and The Medicines Company; has received royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald's Heart Disease); is a site coinvestigator for Biotronik, Boston Scientific, and St. Jude Medical; is a trustee of the American College of Cardiology; and has performed unfunded research for FlowCo, PLx Pharma, and Takeda. Dr. Bonaca has received consulting fees from AstraZeneca, Merck, Bayer, and Roche Diagnostics. Dr. Bansilal has received consulting fees and a research grant from AstraZeneca. Dr. Angiolillo has received consulting fees or honoraria from Sanofi, Eli Lilly, Daiichi-Sankyo, The Medicines Company, AstraZeneca, Merck, Abbott Vascular, and PLx Pharma; has participated in review activities from CeloNova, Johnson & Johnson, and St. Jude Medical; and has received institutional payments for grants from GlaxoSmithKline, Eli Lilly, Daiichi-Sankyo, The Medicines Company, AstraZeneca, Janssen Pharmaceuticals, Inc., Osprey Medical, Inc., Novartis, CSL Behring, and Gilead. Dr. Cohen is on the Speakers Bureau of and is an advisory board consultant for AstraZeneca. Dr. Storey has received consultancy fees from AstraZeneca, Aspen, Correvio, PlaqueTec, Thermo Fisher Scientific, and The Medicines Company; has received honoraria from AstraZeneca and Medscape; and has received travel support from AstraZeneca. Dr. Held is an employee of AstraZeneca. Dr. Braunwald has received research grant support through Brigham and Women's Hospital from AstraZeneca, Daiichi-Sankyo, GlaxoSmithKline, Merck, Sanofi, and Novartis; and has served as a consultant for The Medicines Company, Sanofi, and Theravance (all <=$10,000/year). Dr.; Sabatine has received research grant support through Brigham and Women's Hospital from Abbott Laboratories, Amgen, AstraZeneca, Critical Diagnostics, Daiichi-Sankyo, Eisai, Gilead, GlaxoSmithKline, Intarcia, Merck, Novartis, Poxel, Roche Diagnostics, Sanofi, and Takeda; and has received consultancy fees from Alnylam, AstraZeneca, CVS Caremark, and Merck. Dr. Steg has received significant research grants from Sanofi, Merck, and Servier; has received other personal fees and nonfinancial support from AstraZeneca, Sanofi, and Servier; and has received personal fees from Amarin, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Daiichi-Sankyo, Lilly, Merck, Janssen, Novartis, Medtronic, Pfizer, Regeneron, Roche, The Medicines Company, and GlaxoSmithKline. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 25 TC 9 Z9 9 U1 0 U2 3 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 JUN 14 PY 2016 VL 67 IS 23 BP 2732 EP 2740 DI 10.1016/j.jacc.2016.03.529 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DN7RF UT WOS:000377274300005 PM 27046160 ER PT J AU Isselbacher, EM AF Isselbacher, Eric M. TI The Natural History of Thoracic Aortic Disease So Much Left to Learn SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE aortic dissection; bicuspid aortic valve; Marfan syndrome; thoracic aortic aneurysm ID MARFAN-SYNDROME; DISSECTION; VALVES; DILATATION; PREDICTOR; DIAMETER; CM C1 [Isselbacher, Eric M.] Massachusetts Gen Hosp, Thorac Aort Ctr, 55 Fruit St,YAW 5800, Boston, MA 02114 USA. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,YAW 5800, Boston, MA 02114 USA. [Isselbacher, Eric M.] Harvard Univ, Sch Med, Boston, MA USA. RP Isselbacher, EM (reprint author), Massachusetts Gen Hosp, Thorac Aort Ctr, 55 Fruit St,YAW 5800, Boston, MA 02114 USA. EM eisselbacher@mgh.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN 14 PY 2016 VL 67 IS 23 BP 2755 EP 2757 DI 10.1016/j.jacc.2016.04.007 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DN7RF UT WOS:000377274300008 PM 27282896 ER PT J AU Machiela, MJ Zhou, WY Karlins, E Sampson, JN Freedman, ND Yang, Q Hicks, B Dagnall, C Hautman, C Jacobs, KB Abnet, CC Aldrich, MC Amos, C Amundadottir, LT Arslan, AA Beane-Freeman, LE Berndt, SI Black, A Blot, WJ Bock, CH Bracci, PM Brinton, LA Bueno-De-Mesquita, HB Burdett, L Buring, JE Butler, MA Canzian, F Carreon, T Chaffee, KG Chang, IS Chatterjee, N Chen, C Chen, C Chen, KX Chung, CC Cook, LS Bou, MC Cullen, M Davis, FG De Vivo, I Ding, T Doherty, J Duell, EJ Epstein, CG Fan, JH Figueroa, JD Fraumeni, JF Friedenreich, CM Fuchs, CS Gallinger, S Gao, YT Gapstur, SM Garcia-Closas, M Gaudet, MM Gaziano, JM Giles, GG Gillanders, EM Giovannucci, EL Goldin, L Goldstein, AM Haiman, CA Hallmans, G Hankinson, SE Harris, CC Henriksson, R Holly, EA Hong, YC Hoover, RN Hsiung, CA Hu, N Hu, W Hunter, DJ Hutchinson, A Jenab, M Johansen, C Khaw, KT Kim, HN Kim, YH Kim, YT Klein, AP Klein, R Koh, WP Kolonel, LN Kooperberg, C Kraft, P Krogh, V Kurtz, RC LaCroix, A Lan, Q Landi, MT Le Marchand, L Li, DH Liang, XL Liao, LM Lin, DX Liu, JJ Lissowska, J Lu, LG Magliocco, AM Malats, N Matsuo, K McNeill, LH McWilliams, RR Melin, BS Mirabello, L Moore, L Olson, SH Orlow, I Park, JY Patino-Garcia, A Peplonska, B Peters, U Petersen, GM Pooler, L Prescott, J Prokunina-Olsson, L Purdue, MP Qiao, YL Rajaraman, P Real, FX Riboli, E Risch, HA Rodriguez-Santiago, B Ruder, AM Savage, SA Schumacher, F Schwartz, AG Schwartz, KL Seow, A Setiawan, VW Severi, G Shen, H Sheng, X Shin, MH Shu, XO Silverman, DT Spitz, MR Stevens, VL Stolzenberg-Solomon, R Stram, D Tang, ZZ Taylor, PR Teras, LR Tobias, GS Van den Berg, D Visvanathan, K Wacholder, S Wang, JC Wang, ZM Wentzensen, N Wheeler, W White, E Wiencke, JK Wolpin, BM Wong, MP Wu, C Wu, TC Wu, XF Wu, YL Wunder, JS Xia, L Yang, HP Yang, PC Yu, K Zanetti, KA Zeleniuch-Jacquotte, A Zheng, W Zhou, B Ziegler, RG Perez-Jurado, LA Caporaso, NE Rothman, N Tucker, M Dean, MC Yeager, M Chanock, SJ AF Machiela, Mitchell J. Zhou, Weiyin Karlins, Eric Sampson, Joshua N. Freedman, Neal D. Yang, Qi Hicks, Belynda Dagnall, Casey Hautman, Christopher Jacobs, Kevin B. Abnet, Christian C. Aldrich, Melinda C. Amos, Christopher Amundadottir, Laufey T. Arslan, Alan A. Beane-Freeman, Laura E. Berndt, Sonja I. Black, Amanda Blot, William J. Bock, Cathryn H. Bracci, Paige M. Brinton, Louise A. Bueno-de-Mesquita, H. Bas Burdett, Laurie Buring, Julie E. Butler, Mary A. Canzian, Federico Carreon, Tania Chaffee, Kari G. Chang, I-Shou Chatterjee, Nilanjan Chen, Chu Chen, Constance Chen, Kexin Chung, Charles C. Cook, Linda S. Bou, Marta Crous Cullen, Michael Davis, Faith G. De Vivo, Immaculata Ding, Ti Doherty, Jennifer Duell, Eric J. Epstein, Caroline G. Fan, Jin-Hu Figueroa, Jonine D. Fraumeni, Joseph F. Friedenreich, Christine M. Fuchs, Charles S. Gallinger, Steven Gao, Yu-Tang Gapstur, Susan M. Garcia-Closas, Montserrat Gaudet, Mia M. Gaziano, J. Michael Giles, Graham G. Gillanders, Elizabeth M. Giovannucci, Edward L. Goldin, Lynn Goldstein, Alisa M. Haiman, Christopher A. Hallmans, Goran Hankinson, Susan E. Harris, Curtis C. Henriksson, Roger Holly, Elizabeth A. Hong, Yun-Chul Hoover, Robert N. Hsiung, Chao A. Hu, Nan Hu, Wei Hunter, David J. Hutchinson, Amy Jenab, Mazda Johansen, Christoffer Khaw, Kay-Tee Kim, Hee Nam Kim, Yeul Hong Kim, Young Tae Klein, Alison P. Klein, Robert Koh, Woon-Puay Kolonel, Laurence N. Kooperberg, Charles Kraft, Peter Krogh, Vittorio Kurtz, Robert C. LaCroix, Andrea Lan, Qing Landi, Maria Teresa Le Marchand, Loic Li, Donghui Liang, Xiaolin Liao, Linda M. Lin, Dongxin Liu, Jianjun Lissowska, Jolanta Lu, Lingeng Magliocco, Anthony M. Malats, Nuria Matsuo, Keitaro McNeill, Lorna H. McWilliams, Robert R. Melin, Beatrice S. Mirabello, Lisa Moore, Lee Olson, Sara H. Orlow, Irene Park, Jae Yong Patino-Garcia, Ana Peplonska, Beata Peters, Ulrike Petersen, Gloria M. Pooler, Loreall Prescott, Jennifer Prokunina-Olsson, Ludmila Purdue, Mark P. Qiao, You-Lin Rajaraman, Preetha Real, Francisco X. Riboli, Elio Risch, Harvey A. Rodriguez-Santiago, Benjamin Ruder, Avima M. Savage, Sharon A. Schumacher, Fredrick Schwartz, Ann G. Schwartz, Kendra L. Seow, Adeline Setiawan, Veronica Wendy Severi, Gianluca Shen, Hongbing Sheng, Xin Shin, Min-Ho Shu, Xiao-Ou Silverman, Debra T. Spitz, Margaret R. Stevens, Victoria L. Stolzenberg-Solomon, Rachael Stram, Daniel Tang, Ze-Zhong Taylor, Philip R. Teras, Lauren R. Tobias, Geoffrey S. Van den Berg, David Visvanathan, Kala Wacholder, Sholom Wang, Jiu-Cun Wang, Zhaoming Wentzensen, Nicolas Wheeler, William White, Emily Wiencke, John K. Wolpin, Brian M. Wong, Maria Pik Wu, Chen Wu, Tangchun Wu, Xifeng Wu, Yi-Long Wunder, Jay S. Xia, Lucy Yang, Hannah P. Yang, Pan-Chyr Yu, Kai Zanetti, Krista A. Zeleniuch-Jacquotte, Anne Zheng, Wei Zhou, Baosen Ziegler, Regina G. Perez-Jurado, Luis A. Caporaso, Neil E. Rothman, Nathaniel Tucker, Margaret Dean, Michael C. Yeager, Meredith Chanock, Stephen J. TI Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome SO NATURE COMMUNICATIONS LA English DT Article ID DETECTABLE CLONAL MOSAICISM; SOMATIC MOSAICISM; HUMAN GENOME; CANCER; BLOOD; METHYLATION; CELLS; HEMATOPOIESIS; ANEUPLOIDIES; MUTATION AB To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases. C1 [Machiela, Mitchell J.; Zhou, Weiyin; Karlins, Eric; Sampson, Joshua N.; Freedman, Neal D.; Yang, Qi; Hicks, Belynda; Dagnall, Casey; Hautman, Christopher; Abnet, Christian C.; Amundadottir, Laufey T.; Beane-Freeman, Laura E.; Berndt, Sonja I.; Black, Amanda; Brinton, Louise A.; Burdett, Laurie; Chatterjee, Nilanjan; Chung, Charles C.; Cullen, Michael; Epstein, Caroline G.; Figueroa, Jonine D.; Fraumeni, Joseph F.; Goldin, Lynn; Goldstein, Alisa M.; Hoover, Robert N.; Hu, Nan; Hu, Wei; Hutchinson, Amy; Lan, Qing; Landi, Maria Teresa; Liao, Linda M.; Mirabello, Lisa; Moore, Lee; Prokunina-Olsson, Ludmila; Purdue, Mark P.; Rajaraman, Preetha; Savage, Sharon A.; Seow, Adeline; Silverman, Debra T.; Stolzenberg-Solomon, Rachael; Taylor, Philip R.; Tobias, Geoffrey S.; Wacholder, Sholom; Wang, Zhaoming; Wentzensen, Nicolas; Yang, Hannah P.; Yu, Kai; Ziegler, Regina G.; Caporaso, Neil E.; Rothman, Nathaniel; Tucker, Margaret; Dean, Michael C.; Yeager, Meredith; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Zhou, Weiyin; Karlins, Eric; Yang, Qi; Hicks, Belynda; Dagnall, Casey; Hautman, Christopher; Jacobs, Kevin B.; Burdett, Laurie; Chung, Charles C.; Cullen, Michael; Hutchinson, Amy; Wang, Zhaoming; Yeager, Meredith] Leidos Biomed Res Inc, Div Canc Epidemiol & Genet, Natl Canc Inst, Canc Genom Res Lab, Bethesda, MD 20892 USA. [Jacobs, Kevin B.] Bioinformed LLC, Gaithersburg, MD 20877 USA. [Aldrich, Melinda C.] Vanderbilt Univ, Sch Med, Dept Thorac Surg, Nashville, TN 37232 USA. [Aldrich, Melinda C.; Blot, William J.; Zheng, Wei] Vanderbilt Univ, Med Ctr, Vanderbilt Epidemiol Ctr, Dept Med,Div Epidemiol, Nashville, TN 37232 USA. [Amos, Christopher] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA. [Arslan, Alan A.] NYU, Sch Med, Dept Obstet & Gynecol, New York, NY 10016 USA. [Arslan, Alan A.] NYU, Sch Med, Dept Environm Med, New York, NY 10016 USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Inst Canc, New York, NY 10016 USA. [Blot, William J.] Int Epidemiol Inst, Rockville, MD 20850 USA. [Bock, Cathryn H.; Schwartz, Ann G.] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI 48201 USA. [Bock, Cathryn H.; Schwartz, Ann G.] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI 48201 USA. [Bracci, Paige M.; Holly, Elizabeth A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis DCD, Bilthoven 3721, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ Med Ctr, Dept Gastroenterol & Hepatol, NL-3584 CX Utrecht, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London SW7 2AZ, England. [Bueno-de-Mesquita, H. Bas] Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur 50603, Malaysia. [Buring, Julie E.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Butler, Mary A.; Carreon, Tania; Ruder, Avima M.] NIOSH, Ctr Dis Control & Prevent, Cincinnati, OH 45226 USA. [Canzian, Federico] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany. [Chaffee, Kari G.; Petersen, Gloria M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Chang, I-Shou] Natl Hlth Res Inst, Natl Inst Canc Res, Zhunan 35053, Taiwan. [Chen, Chu; Kooperberg, Charles; LaCroix, Andrea; Peters, Ulrike; White, Emily] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Chen, Constance; Bou, Marta Crous; De Vivo, Immaculata; Hunter, David J.; Kraft, Peter; Prescott, Jennifer] Harvard Univ, Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA. [Chen, Kexin] Tianjin Med Univ, Canc Inst & Hosp, Dept Epidemiol & Biostat, Tianjin 300040, Peoples R China. [Cook, Linda S.] Univ New Mexico, Albuquerque, NM 87131 USA. [Bou, Marta Crous; De Vivo, Immaculata; Fuchs, Charles S.; Giovannucci, Edward L.; Hankinson, Susan E.; Hunter, David J.; Prescott, Jennifer; Wolpin, Brian M.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Bou, Marta Crous; De Vivo, Immaculata; Fuchs, Charles S.; Giovannucci, Edward L.; Hankinson, Susan E.; Hunter, David J.; Prescott, Jennifer; Wolpin, Brian M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Davis, Faith G.] Univ Alberta, Sch Publ Hlth, Dept Publ Hlth Sci, Edmonton, AB T6G 2R3, Canada. [Ding, Ti; Tang, Ze-Zhong] Shanxi Canc Hosp, Taiyuan 030013, Shanxi, Peoples R China. [Doherty, Jennifer] Dartmouth Coll, Geisel Sch Med, Lebanon, NH 03755 USA. [Duell, Eric J.] Catalan Inst Oncol ICO IDIBELL, Bellvitge Biomed Res Inst, Canc Epidemiol Res Program, Unit Nutr & Canc, Barcelona 08908, Spain. Shanghai Canc Inst, Shanghai 200032, Peoples R China. [Friedenreich, Christine M.] Alberta Hlth Serv, Canc Control Alberta, Dept Populat Hlth Res, Calgary, AB T2N 2T9, Canada. [Fuchs, Charles S.; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Gallinger, Steven] Samuel Lunenfeld Res Inst, Fred A Litwin Ctr Canc Genet, Toronto, ON M5G 1X5, Canada. [Gao, Yu-Tang] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst,Dept Epidemiol, Shanghai 200032, Peoples R China. [Gapstur, Susan M.; Gaudet, Mia M.; Stevens, Victoria L.; Teras, Lauren R.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA. [Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England. [Garcia-Closas, Montserrat] Inst Canc Res, Breakthrough Breast Canc Ctr, Sutton SM2 5NG, Surrey, England. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Gaziano, J. Michael] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Gaziano, J. Michael] Vet Affairs Boston Healthcare Syst, VA Cooperat Studies Programs, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02130 USA. [Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Canc Epidemiol Ctr, Canc Council Victoria, Melbourne, Vic 3010, Australia. [Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia. [Gillanders, Elizabeth M.; Zanetti, Krista A.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Haiman, Christopher A.; Schumacher, Fredrick; Setiawan, Veronica Wendy; Stram, Daniel; Van den Berg, David] Univ So Calif, Keck Sch Med, Dept Prevent Med, Div Biostat, Los Angeles, CA 90033 USA. [Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med Nutr Res, S-90187 Umea, Sweden. [Hankinson, Susan E.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA. [Harris, Curtis C.] NCI, Ctr Canc Res, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. [Henriksson, Roger; Melin, Beatrice S.] Umea Univ, Dept Radiat Sci Oncol, S-90187 Umea, Sweden. [Hong, Yun-Chul] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 151742, South Korea. [Hsiung, Chao A.] Natl Hlth Res Inst, Inst Populat Hlth Sci, Zhunan 35053, Taiwan. [Hunter, David J.] Harvard & MIT, Broad Inst, Cambridge, MA 02142 USA. [Jenab, Mazda] WHO, IARC, F-69372 Lyon, France. [Johansen, Christoffer] Rigshosp, Finsen Ctr, Oncol, DK-2100 Copenhagen, Denmark. [Johansen, Christoffer] Danish Canc Soc, Res Ctr, Unit Survivorship Res, DK-2100 Copenhagen, Denmark. [Khaw, Kay-Tee] Univ Cambridge, Sch Clin Med, Cambridge CB2 1TN, England. [Kim, Hee Nam] Chonnam Natl Univ, Ctr Creat Biomed Scientists, Gwangju 500757, South Korea. [Kim, Yeul Hong] Korea Univ, Anam Hosp, Coll Med, Dept Internal Med,Div Oncol Hematol, Seoul 151742, South Korea. [Kim, Young Tae] Seoul Natl Univ, Coll Med, Canc Res Inst, Dept Thorac & Cardiovasc Surg, Seoul 03080, South Korea. [Klein, Alison P.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA. [Klein, Robert] Mem Sloan Kettering Canc Ctr, Program Canc Biol & Genet, New York, NY 10065 USA. [Koh, Woon-Puay] Duke NUS Grad Med Sch, Singapore 169857, Singapore. [Koh, Woon-Puay; Seow, Adeline] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 119077, Singapore. [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96813 USA. [Krogh, Vittorio] Fdn IRCCS Ist Nazl Tumori, I-20133 Milan, Italy. [Kurtz, Robert C.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA. [Li, Donghui] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Liang, Xiaolin; Olson, Sara H.; Orlow, Irene] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Lin, Dongxin; Wu, Chen] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Etiol & Carcinogenesis, Beijing 100730, Peoples R China. [Lin, Dongxin; Wu, Chen] Peking Union Med Coll, Beijing 100730, Peoples R China. [Lin, Dongxin; Wu, Chen] Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing 100730, Peoples R China. [Liu, Jianjun] Genome Inst Singapore, Dept Human Genet, Singapore 138672, Singapore. [Liu, Jianjun] Anhui Med Univ, Sch Life Sci, Hefei 230032, Peoples R China. [Lissowska, Jolanta] Maria Sklodowska Curie Canc Ctr & Inst Oncol, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland. [Lu, Lingeng; Risch, Harvey A.] Yale Univ, Sch Publ Hlth, New Haven, CT 06510 USA. [Magliocco, Anthony M.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Malats, Nuria; Real, Francisco X.] Spanish Natl Canc Res Ctr CNIO, Madrid 28029, Spain. [Matsuo, Keitaro] Aichi Canc Ctr, Res Inst, Div Mol Med, Nagoya, Aichi 4648681, Japan. [McNeill, Lorna H.] Univ Texas MD Anderson Canc Ctr, Duncan Family Inst, Dept Hlth Dispar Res, Div OVP Canc Prevent & Populat Sci, Houston, TX 77030 USA. [McNeill, Lorna H.] Univ Texas MD Anderson Canc Ctr, Duncan Family Inst, Ctr Community Engaged Translat Res, Houston, TX 77030 USA. [McWilliams, Robert R.] Mayo Clin, Dept Oncol, Rochester, MN 55905 USA. [Park, Jae Yong] Kyungpook Natl Univ, Med Ctr, Lung Canc Ctr, Daegu 101, South Korea. [Patino-Garcia, Ana] Univ Navarra, Univ Navarra Clin, Navarra Inst Hlth Res, IdiSNA,Dept Pediat, E-31080 Pamplona, Spain. [Peplonska, Beata] Nofer Inst Occupat Med, PL-91348 Lodz, Poland. [Pooler, Loreall; Sheng, Xin; Xia, Lucy] Univ So Calif, Los Angeles, CA 90007 USA. [Qiao, You-Lin] Chinese Acad Med Sci, Canc Inst Hosp, Dept Epidemiol, Beijing 100730, Peoples R China. [Real, Francisco X.; Rodriguez-Santiago, Benjamin; Perez-Jurado, Luis A.] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona 08002, Spain. [Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Div Epidemiol & Biostat, London SW7 2AZ, England. [Rodriguez-Santiago, Benjamin; Perez-Jurado, Luis A.] Ctr Invest Biomed Red Enfermedades Raras CIBERER, Barcelona 28029, Spain. [Rodriguez-Santiago, Benjamin] QGenomics, Quantitat Genom Med Lab, Barcelona 08003, Spain. [Schwartz, Kendra L.] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI 48201 USA. [Schwartz, Kendra L.] Wayne State Univ, Sch Med, Dept Family Med & Publ Hlth Sci, Detroit, MI 48201 USA. [Severi, Gianluca] Human Genet Fdn HuGeF, I-10126 Turin, Italy. [Shen, Hongbing] Nanjing Med Univ, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing 210029, Jiangsu, Peoples R China. [Shen, Hongbing] Nanjing Med Univ, Sch Publ Hlth, Dept Epidemiol, Nanjing 210029, Jiangsu, Peoples R China. [Shin, Min-Ho] Chonnam Natl Univ, Sch Med, Dept Prevent Med, Gwanju 501746, South Korea. [Shu, Xiao-Ou] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Dept Med, Nashville, TN 37232 USA. [Spitz, Margaret R.] Baylor Coll Med, Houston, TX 77030 USA. [Visvanathan, Kala] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. [Wang, Jiu-Cun] Fudan Univ, Sch Life Sci, Key Lab Contemporary Anthropol, Minist Educ, Shanghai 200433, Peoples R China. [Wang, Jiu-Cun] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China. [Wheeler, William] Informat Management Serv Inc, Calverton, MD 20904 USA. [Wiencke, John K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Wong, Maria Pik] Univ Hong Kong, Li Ka Shing Fac Med, Dept Pathol, Hong Kong, Hong Kong, Peoples R China. [Wu, Tangchun] Huazhong Univ Sci & Technol, Sch Publ Hlth, Inst Occupat Med, Wuhan 430400, Peoples R China. [Wu, Tangchun] Huazhong Univ Sci & Technol, Sch Publ Hlth, Key Lab Environm & Hlth, Minist Educ, Wuhan 430400, Peoples R China. [Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Wu, Yi-Long] Guangdong Gen Hosp, Guangdong Lung Canc Inst, Guangzhou 515200, Guangdong, Peoples R China. [Wu, Yi-Long] Guangdong Acad Med Sci, Guangzhou 515200, Guangdong, Peoples R China. [Wunder, Jay S.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. [Yang, Pan-Chyr] Natl Taiwan Univ, Coll Med, Dept Internal Med, Taipei 10617, Taiwan. [Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Populat Hlth, New York, NY 10016 USA. [Zhou, Baosen] China Med Univ, Sch Publ Hlth, Dept Epidemiol, Shenyang 110001, Peoples R China. RP Chanock, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM chanocks@mail.nih.gov RI Krogh, Vittorio/K-2628-2016; Abnet, Christian/C-4111-2015; Tobias, Geoffrey/M-4135-2016; Qiao, You-Lin/B-4139-2012; Zheng, Wei/O-3351-2013; Beane Freeman, Laura/C-4468-2015 OI Krogh, Vittorio/0000-0003-0122-8624; Abnet, Christian/0000-0002-3008-7843; Tobias, Geoffrey/0000-0002-2878-8253; Qiao, You-Lin/0000-0001-6380-0871; Zheng, Wei/0000-0003-1226-070X; Beane Freeman, Laura/0000-0003-1294-4124 FU Broad Center for Genotyping and Analysis [U01HG04424]; Cancer Prevention Study-II (American Cancer Society); Center for Inherited Disease Research [U01HG004438, HHSN268200782096C]; Endometrial cancer [ROl CA 134958]; Fred Hutchinson Cancer Research Center (funds from the Fred Hutchinson Cancer Research Center and National Institute of Health) [R35 CA 39779, RO1 CA 75977, R03 CA 80636, NO1 HD 2 3166, KO5 CA 92002, CA 105212, RO1 CA87538]; Fudan Lung Cancer Study Ministry of Health [201002007]; Ministry of Science and Technology [2011BAIO9B00]; National S&T Major Special Project [2011ZX09102-010-01]; China National High-Tech Research and Development Program [2012AA02A517, 2012AA02A518]; National Science Foundation of China [30890034]; National Basic Research Program [2012CB944600]; Scientific and Technological Support Plans from Jiangsu Province [BE2010715]; Genes and Environment in Lung Cancer, Singapore Study (National Medical Research Council Singapore) [NMRC/0897/2004, NMRC/1075/2006]; Agency for Science, Technology and Research (A*STAR) of Singapore; National Research Program on Genomic Medicine in Taiwan [DOH98-TD-G-111-015]; National Research Program for Biopharmaceuticals in Taiwan [DOH 100-TD-PB-111TM013]; National Science Council, Taiwan [NSC 100-2319-B-400-001]; Guangdong Study (Foundation of Guangdong Science and Technology Department [2006B60101010, 2007A032000002, 2011A030400010]; Guangzhou Science and Information Technology Bureau [2011Y2-00014]; Chinese Lung Cancer Research Foundation; National Natural Science Foundation of China [81101549]; Natural Science Foundation of Guangdong Province [S2011010000792]; Hong Kong Study (General Research Fund of Research Grant Council, Hong Kong) [781511M]; Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH; Intramural Research Program of the NIH, National Library of Medicine; Intramural Research Program of the National Institute for Occupational Safety and Health; Ministry of Health, Labor, and Welfare for Research on Applying Health Technology; National Cancer Center Research and Development Fund; NCI [R01-CA121210]; Korea Health Technology R&D Project (Korea Health Industry Development Institute (KHIDI); Ministry of Health & Welfare, Republic of Korea [HI14C0066]; Ministry of Health [201002007]; Melanoma [NCI R29CA70334, R01CA100264, P50CA093459]; National Research Foundation of Korea (NRF); Korea government (MSIP) [NRF-2014R1A2A2A05003665]; NLCS (China National High-Tech Research and Development Program Grant [2009AA022705]; Priority Academic Program Development of Jiangsu Higher Education Institution; National Key Basic Research Program Grant [2011CB503805]; Nurses' Health Study [P01 CA87969, ROl CA49449]; Yunnan Lung Cancer Study (Intramural program of U.S. National Institutes of Health; National Cancer Institute; NIH/NCI [K07 CA 172294]; Women's Health Initiative (National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services) [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; Tianjin Cancer Institute and Hospital, National Foundation for Cancer Research US; [U01 CA164973]; [U01 CA098758] FX Some individuals, studies, and centers received individual support as follows: Broad Center for Genotyping and Analysis (U01HG04424); Cancer Prevention Study-II (American Cancer Society); Center for Inherited Disease Research (U01HG004438, HHSN268200782096C); Endometrial cancer (ROl CA 134958); Fred Hutchinson Cancer Research Center (funds from the Fred Hutchinson Cancer Research Center and National Institute of Health grants (R35 CA 39779, RO1 CA 75977, R03 CA 80636, NO1 HD 2 3166, KO5 CA 92002, CA 105212 and RO1 CA87538)); Fudan Lung Cancer Study (Ministry of Health (201002007); Ministry of Science and Technology (2011BAIO9B00); National S&T Major Special Project (2011ZX09102-010-01); China National High-Tech Research and Development Program (2012AA02A517, 2012AA02A518); National Science Foundation of China (30890034); National Basic Research Program (2012CB944600); Scientific and Technological Support Plans from Jiangsu Province (BE2010715)); Gene-Environment Association Studies (Coordinating Center:U01 HG004446, Manuscript preparation: P01-GM099568); Genes and Environment in Lung Cancer, Singapore Study (National Medical Research Council Singapore grant (NMRC/0897/2004, NMRC/1075/2006); Agency for Science, Technology and Research (A*STAR) of Singapore); Genetic Epidemiological Study of Lung Adenocarcinoma (National Research Program on Genomic Medicine in Taiwan (DOH98-TD-G-111-015); National Research Program for Biopharmaceuticals in Taiwan (DOH 100-TD-PB-111TM013); National Science Council, Taiwan (NSC 100-2319-B-400-001)); Guangdong Study (Foundation of Guangdong Science and Technology Department (2006B60101010, 2007A032000002, 2011A030400010); Guangzhou Science and Information Technology Bureau (2011Y2-00014); Chinese Lung Cancer Research Foundation; National Natural Science Foundation of China (81101549); Natural Science Foundation of Guangdong Province (S2011010000792)); Hong Kong Study (General Research Fund of Research Grant Council, Hong Kong (781511M)); Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH; Intramural Research Program of the NIH, National Library of Medicine; Intramural Research Program of the National Institute for Occupational Safety and Health; Japanese Female Lung Cancer Collaborative Study (Grants-in-Aid from the Ministry of Health, Labor, and Welfare for Research on Applying Health Technology and for the 3rd-term Comprehensive 10-year Strategy for Cancer Control; National Cancer Center Research and Development Fund; Grant-in-Aid for Scientific Research on Priority Areas and on Innovative Area from the Ministry of Education, Science, Sports, Culture and Technology of Japan; NCI (R01-CA121210)); Korea Health Technology R&D Project (Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C0066)); Lung cancer (ZO1CP010200); Lung health (U01HG004738); Ministry of Health (201002007); Ministry of Science and Technology (2011BAIO9B00); Melanoma (NCI R29CA70334, R01CA100264, P50CA093459); Multiethnic Cohort Study (Infrastructure grant (U01 CA164973) and U01 CA098758); National Research Foundation of Korea (NRF) (funded by the Korea government (MSIP) (NRF-2014R1A2A2A05003665)); NLCS (China National High-Tech Research and Development Program Grant (2009AA022705); Priority Academic Program Development of Jiangsu Higher Education Institution; National Key Basic Research Program Grant (2011CB503805)); Nurses' Health Study (P01 CA87969, ROl CA49449); Nurses' Health Study II (UM1 CA176726, ROl 6; 7262); OpPancreatic cancer (Mayo Clinic SPORE in Pancreatic Cancer: P50CA102701); Prostate cancer (U01HG004726, NCI: CA63464, CA54281, CA1326792, RC2 CA148085); Shanghai Women's Health Cohort Study (National Institutes of Health (R37 CA70867); National Cancer Institute intramural research program; NCI Intramural Research Program contract (NO2 CP1101066)); Shenyang Lung Cancer Study (National Nature Science Foundation of China (81102194); Liaoning Provincial Department of Education (LS2010168); China Medical Board (00726)); Singapore Chinese Health Study (NIH grants: NCI ROl CA55069, R35 CA53890, ROl CA80205, and ROl CA144034); South Korea Multi-Center Lung Cancer Study (National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (2011-0016106); National R&D Program for Cancer Control, Ministry of Health &Welfare, Republic of Korea (0720550-2); (A010250)); Tianjin Lung Cancer Study (Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT); China (IRT1076), Tianjin Cancer Institute and Hospital, National Foundation for Cancer Research US); University of Texas MD Anderson Cancer Center (institutional support for the Center for Translational and Public Health Genomics (NIH grant P50 CA 91846)); Women's Health Initiative (National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C); Wuhan lung cancer study (National Key Basic Research and Development Program (2011CB503800)) and Yunnan Lung Cancer Study (Intramural program of U.S. National Institutes of Health; National Cancer Institute). Melinda C. Aldrich was supported by NIH/NCI grant K07 CA 172294. We would like to thank the participants and staff of the NHS and NHSII cohorts for their valuable contributions as well as the following state registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. This study was approved by the Connecticut Department of Public Health (DPH) Human Investigations Committee. Certain data used in this publication were obtained from the DPH. The authors assume full responsibility for the analyses and interpretation of these data. The Women's Health Initiative would like to acknowledge the following individuals for their participation: Program Office: (National Heart, Lung, and Blood Institute, Bethesda, Maryland) Jacques Rossouw, Shari Ludlam, Dale Burwen, Joan McGowan, Leslie Ford, and Nancy Geller; Clinical Coordinating Center: (Fred Hutchinson Cancer Research Center, Seattle, WA) Garnet Anderson, Ross Prentice, Andrea LaCroix, and Charles Kooperberg; Investigators and Academic Centers: (Brigham and Women's Hospital, Harvard Medical School, Boston, MA) JoAnn E. Manson; (MedStar Health Research Institute/Howard University, Washington, DC) Barbara V. Howard; (Stanford Prevention Research Center, Stanford, CA). Marcia L. Stefanick; (The Ohio State University, Columbus, OH) Rebecca Jackson; (University of Arizona, Tucson/Phoenix, AZ) Cynthia A. Thomson; (University at Buffalo, Buffalo, NY) Jean Wactawski-Wende; (University of Florida, Gainesville/Jacksonville, FL) Marian Limacher; (University of Iowa, Iowa City/Davenport, IA) Robert Wallace; (University of Pittsburgh, Pittsburgh, PA) Lewis Kuller; (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker.; Women's Health Initiative Memory Study: (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker. NR 40 TC 0 Z9 0 U1 13 U2 19 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 JUN 13 PY 2016 VL 7 AR 118431 DI 10.1038/ncomms118431 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DP3IY UT WOS:000378387800001 ER PT J AU Paolella, BR Stiles, CD AF Paolella, Brenton R. Stiles, Charles D. TI Gliomas "Dope Up'' for Growth SO CANCER CELL LA English DT Editorial Material ID STEM-CELLS; DOPAMINE; NEUROGENESIS; BRAIN; DRUGS AB An emerging body of data highlights trophic functions of neurotransmitters on proliferation and differentiation of normal neural progenitors. In this issue of Cancer Cell, Dolma et al. document pro-survival functions of a neurotransmitter receptor in glioma progenitor cells, with practical overtones for therapy. C1 [Paolella, Brenton R.; Stiles, Charles D.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. RP Stiles, CD (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. EM charles_stiles@dfci.harvard.edu FU NCI NIH HHS [F32 CA180653] NR 9 TC 0 Z9 0 U1 3 U2 4 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 JUN 13 PY 2016 VL 29 IS 6 BP 778 EP 780 DI 10.1016/j.ccell.2016.05.010 PG 4 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DO7AB UT WOS:000377933500005 PM 27300432 ER PT J AU Groner, AC Cato, L de Tribolet-Hardy, J Bernasocchi, T Janouskova, H Melchers, D Houtman, R Cato, ACB Tschopp, P Gu, L Corsinotti, A Zhong, Q Fankhauser, C Fritz, C Poyet, C Wagner, U Guo, T Aebersold, R Garraway, LA Wild, PJ Theurillat, JP Brown, M AF Groner, Anna C. Cato, Laura de Tribolet-Hardy, Jonas Bernasocchi, Tiziano Janouskova, Hana Melchers, Diana Houtman, Rene Cato, Andrew C. B. Tschopp, Patrick Gu, Lei Corsinotti, Andrea Zhong, Qing Fankhauser, Christian Fritz, Christine Poyet, Cedric Wagner, Ulrich Guo, Tiannan Aebersold, Ruedi Garraway, Levi A. Wild, Peter J. Theurillat, Jean-Philippe Brown, Myles TI TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer SO CANCER CELL LA English DT Article ID ANDROGEN-RECEPTOR GENE; MUTATIONAL LANDSCAPE; NUCLEAR RECEPTORS; BREAST-CANCER; SPOP; EXPRESSION; PROGRESSION; COACTIVATOR; GROWTH; PHOSPHORYLATION AB Androgen receptor (AR) signaling is a key driver of prostate cancer (PC). While androgen-deprivation therapy is transiently effective in advanced disease, tumors often progress to a lethal castration-resistant state (CRPC). We show that recurrent PC-driver mutations in speckle-type POZ protein (SPOP) stabilize the TRIM24 protein, which promotes proliferation under low androgen conditions. TRIM24 augments AR signaling, and AR and TRIM24 co-activated genes are significantly upregulated in CRPC. Expression of TRIM24 protein increases from primary PC to CRPC, and both TRIM24 protein levels and the AR/TRIM24 gene signature predict disease recurrence. Analyses in CRPC cells reveal that the TRIM24 bromodomain and the AR-interacting motif are essential to support proliferation. These data provide a rationale for therapeutic TRIM24 targeting in SPOP mutant and CRPC patients. C1 [Groner, Anna C.; Cato, Laura; de Tribolet-Hardy, Jonas; Garraway, Levi A.; Brown, Myles] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. [Groner, Anna C.; Cato, Laura; de Tribolet-Hardy, Jonas; Brown, Myles] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Funct Canc Epigenet, 44 Binney St, Boston, MA 02115 USA. [Bernasocchi, Tiziano; Janouskova, Hana; Theurillat, Jean-Philippe] Inst Oncol Res, CH-6500 Bellinzona, Switzerland. [Melchers, Diana; Houtman, Rene] PamGene Int, NL-5211 HH Den Bosch, Netherlands. [Cato, Andrew C. B.] Karlsruhe Inst Technol, Inst Toxicol & Genet, D-76344 Eggenstein Leopoldshafen, Germany. [Tschopp, Patrick] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA. [Gu, Lei] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Newborn Med, Boston, MA 02215 USA. [Gu, Lei] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. [Corsinotti, Andrea] Univ Edinburgh, Sch Biol Sci, Inst Stem Cell Res, MRC Ctr Regenerat Med, Edinburgh EH16 4UU, Midlothian, Scotland. [Corsinotti, Andrea] Univ Tsukuba, Fac Med, Dept Anat & Embryol, Lab Anim Resource Ctr, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan. [Zhong, Qing; Fankhauser, Christian; Fritz, Christine; Wagner, Ulrich; Wild, Peter J.] Univ Zurich Hosp, Inst Surg Pathol, CH-8091 Zurich, Switzerland. [Fankhauser, Christian; Poyet, Cedric] Univ Zurich Hosp, Dept Urol, CH-8091 Zurich, Switzerland. [Guo, Tiannan; Aebersold, Ruedi] ETH, Inst Mol Syst Biol, Dept Biol, CH-8093 Zurich, Switzerland. [Aebersold, Ruedi] Univ Zurich, Fac Sci, CH-8057 Zurich, Switzerland. [Garraway, Levi A.; Theurillat, Jean-Philippe] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Theurillat, Jean-Philippe] Univ Lausanne, CHU Vaudois, CH-1011 Lausanne, Switzerland. RP Brown, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.; Brown, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Funct Canc Epigenet, 44 Binney St, Boston, MA 02115 USA.; Theurillat, JP (reprint author), Inst Oncol Res, CH-6500 Bellinzona, Switzerland.; Theurillat, JP (reprint author), Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.; Theurillat, JP (reprint author), Univ Lausanne, CHU Vaudois, CH-1011 Lausanne, Switzerland. EM jeanp_theurillat@ior.iosi.ch; myles_brown@dfci.harvard.edu RI Cato, Andrew/H-2071-2013; OI Cato, Andrew/0000-0001-8508-3834; Zhong, Qing/0000-0002-5340-301X FU Advanced Postdoc. Mobility fellowship from the Swiss National Science Foundation [P300P3_151145]; NRSA [T32 CA009172-39]; Swiss National Science Foundation [PP00P3_150645]; Swiss Cancer League [KSL-3654-02-2015]; HFSP Long-term Fellowship; Deutsche Krebshilfe [110237]; Promedica foundation; SystemX.ch grant (PhosphoNet PPM) from Swiss initiative in systems biology; NIH [P50 CA090381-13, 5P01 CA163227]; DF/HCC SPORE in Prostate Cancer; Novartis FX We acknowledge Kexin Xu, Fugen Li, Jin Zhao, Jennifer Spangle, and Nancy Hynes for fruitful advice, assistance, and discussion. We thank Andre Fitsche and Martina Storz for excellent histology assistance. We also thank Quang-De Nguyen and Amy Saur Conway for carrying out the orthotopic in vivo studies. A.C.G. is funded by an Advanced Postdoc. Mobility fellowship from the Swiss National Science Foundation (P300P3_151145) and an NRSA Institutional Training Grant (T32 CA009172-39). J.P.T. is funded by a Swiss National Science Foundation Professorship (PP00P3_150645) and a grant from the Swiss Cancer League (KSL-3654-02-2015). P.T. is supported by an HFSP Long-term Fellowship. A.C.B.C. is funded by Deutsche Krebshilfe 110237. Q.Z. is supported by a Promedica foundation grant to Holger Moch. P.J.W. is funded by a SystemX.ch grant (PhosphoNet PPM) from the Swiss initiative in systems biology. L.C. is funded by NIH P50 CA090381-13 (DF/HCC SPORE). M.B. is funded by NIH 5P01 CA163227 and the DF/HCC SPORE in Prostate Cancer. D.M. and R.H. are employees of PamGene International BV. L.A.G. is a consultant for Foundation Medicine, Novartis, Boehringer Ingelheim; and equity holder in Foundation Medicine. He receives sponsored research support from Novartis. M.B. is a consultant for GTx, Novartis, and SV Life Sciences. He receives sponsored research support from Novartis. NR 58 TC 7 Z9 7 U1 12 U2 18 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 JUN 13 PY 2016 VL 29 IS 6 BP 846 EP 858 DI 10.1016/j.ccell.2016.04.012 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DO7AB UT WOS:000377933500011 PM 27238081 ER PT J AU Alshikho, MJ Noureldine, SI Talas, JM Nasimian, A Zazou, S Mobaed, B Nasser, M AF Alshikho, Mohamad J. Noureldine, Salem I. Talas, Joud M. Nasimian, Antoine Zazou, Safi Mobaed, Bashir Nasser, Mahmoud TI Zollinger-Ellison Syndrome Associated with von Recklinghausen Disease: Case Report and Literature Review SO AMERICAN JOURNAL OF CASE REPORTS LA English DT Review DE Gastrinoma; Neurofibromatosis 1; Zollinger-Ellison Syndrome ID NEUROFIBROMATOSIS TYPE-I; NEUROENDOCRINE TUMORS; CUTANEOUS NEUROFIBROMATOSIS; VONRECKLINGHAUSENS DISEASE; CARCINOID-TUMOR; GASTRINOMAS; MANAGEMENT; DUODENUM; LOCALIZATION; DIAGNOSIS AB Objective: Rare co-existance of disease or pathology Background: Pancreatic endocrine tumors (PETs) are rare and can occur as part of neurofibromatosis type 1 (NF1). Gastrinomas are functional PETs that are rarely associated with NF1. Only two cases of their occurrence have been reported in the literature. Case Report: A 28-year-old woman was admitted for further evaluation of epigastric soreness, heartburn, nausea, vomiting, diarrhea, and a significant weight loss. Physical examination was remarkable for cutaneous findings (axillary freckling and multiple cafe-au-lait spots) as well as neurofibromas (dermal, plexiform). A diagnosis of NF1 was confirmed. Esophagogastroduodenoscopy (EGD) revealed multiple ulcers in the duodenum and the upper jejunum. A fasting gastrin level exceeded ten times the normal limit. An abdominal multi-slice 128 computed tomography (CT) scan revealed an oval mass of 26 mm in diameter adjacent to the second segment of the duodenum. The patient was examined carefully to rule out multiple endocrine neoplasia type 1 (MEN1). Surgical resection was performed and a gastrinoma, causing Zollinger-Ellison syndrome (ZES), was diagnosed by histological examinations of the extirpated mass. The serum gastrin level decreased to normal limits shortly after surgery. Continuous follow-up revealed that the symptoms and the EGD findings completely resolved without recurrences. Conclusions: Although NF1 has common skeletal, visual, neurological, and cardiovascular complications, it also has a rare association with duodenal or pancreatic gastrinomas. Vigilance for this possible association is important to promote timely and careful management to help eliminate serious and potentially life-threatening complications. C1 [Alshikho, Mohamad J.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. [Noureldine, Salem I.] Johns Hopkins Univ, Dept Otolaryngol Head & Neck Surg, Baltimore, MD USA. [Talas, Joud M.] Aleppo Univ, Dept Dermatol, Aleppo, Syria. [Nasimian, Antoine] Aleppo Univ, Dept Radiol, Aleppo, Syria. [Zazou, Safi] Aleppo Univ, Dept Gen Internal Med, Aleppo, Syria. [Mobaed, Bashir; Nasser, Mahmoud] Aleppo Univ, Dept Gastroenterol, Aleppo, Syria. RP Alshikho, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. EM malshikho@mgh.harvard.edu NR 27 TC 0 Z9 0 U1 0 U2 2 PU INT SCIENTIFIC LITERATURE, INC PI SMITHTOWN PA 361 FOREST LANE, SMITHTOWN, NY 11787 USA SN 1941-5923 J9 AM J CASE REP JI Am. J. Case Rep. PD JUN 13 PY 2016 VL 17 BP 398 EP 405 AR 898472 DI 10.12659/AJCR.898472 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DO1TK UT WOS:000377561800001 PM 27292293 ER PT J AU Lammer, J Bosiers, M Deloose, K Schmidt, A Zeller, T Wolf, F Lansink, W Sauguet, A Vermassen, F Lauwers, G Scheinert, D Popma, JJ McGreevy, R Rapoza, R Schwartz, LB Jaff, MR AF Lammer, Johannes Bosiers, Marc Deloose, Koen Schmidt, Andrej Zeller, Thomas Wolf, Florian Lansink, Wouter Sauguet, Antoine Vermassen, Frank Lauwers, Geert Scheinert, Dierk Popma, Jeffrey J. McGreevy, Robert Rapoza, Richard Schwartz, Lewis B. Jaff, Michael R. TI Bioresorbable Everolimus-Eluting Vascular Scaffold for Patients With Peripheral Artery Disease (ESPRIT I) 2-Year Clinical and Imaging Results SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE bioresorbable vascular scaffold; drug-eluting stent(s); femoropopliteal artery; peripheral artery disease; poly-L-lactide ID SUPERFICIAL FEMORAL-ARTERY; NITINOL STENT IMPLANTATION; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; RESILIENT RANDOMIZED-TRIAL; BALLOON ANGIOPLASTY; CORONARY-ARTERIES; COATED BALLOON; FOLLOW-UP; LESIONS; PACLITAXEL AB OBJECTIVES This is the first-in-human study of a drug-eluting bioresorbable vascular scaffold (BVS) for treatment of peripheral artery disease (PAD) involving the external iliac artery (EIA) and superficial femoral artery (SFA). BACKGROUND Drug-eluting BVS has shown promise in coronary arteries. METHODS The ESPRIT BVS system is a device-drug combination consisting of an everolimus-eluting poly-L-lactide scaffold. Safety and performance were evaluated in 35 subjects with symptomatic claudication. RESULTS Lesions were located in the SFA (88.6%) and EIA (11.4%). Mean lesion length was 35.7 +/- 16.0 mm. The study device was successfully deployed in 100% of cases, without recoil. Procedure-related minor complications were observed in 3 patients (groin hematoma, dissection). Within 2 years there was 1 unrelated death, but no patients in this cohort had an amputation. At 1 and 2 years, the binary restenosis rates were 12.1% and 16.1%, respectively, and target lesion revascularization was performed in 3 of 34 patients (8.8%) and 4 of 32 patients (11.8%), respectively. The ankle brachial index 0.75 +/- 0.14 improved from pre-procedure to 0.96 +/- 0.16 at 2 years' follow-up. At 2 years, 71.0% of the patients were Rutherford-Becker 0, and 93.5% achieved a maximum walking distance of 1,500 feet. CONCLUSIONS The safety of the ESPRIT BVS was demonstrated with no procedure or device-related deaths or amputations within 2 years. The low occurrence of revascularizations was consistent with duplex-ultrasonography showing sustained patency at 2-years. (A Clinical Evaluation of the Abbott Vascular ESPRIT BVS [Bioresorbable Vascular Scaffold] System [ESPRIT I]; NCT01468974) (C) 2016 by the American College of Cardiology Foundation. C1 [Lammer, Johannes; Wolf, Florian] Med Univ Vienna, Cardiovasc & Intervent Radiol Dept, Vienna, Austria. [Bosiers, Marc] Sint Blasius Hosp, Dept Vasc Surg, Dendermonde, Belgium. [Deloose, Koen; Scheinert, Dierk] Univ Leipzig, Dept Intervent Angiol, D-04109 Leipzig, Germany. [Schmidt, Andrej; Zeller, Thomas] Univ Herzzentrum Freiburg Bad Krozingen, Dept Angiol, Bad Krozingen, Germany. [Lansink, Wouter; Lauwers, Geert] Oost Limburg Ziekenhuis, Vaatctr, Genk, Belgium. [Sauguet, Antoine] Clin Pasteur, Dept Gen Intervent Cardiol, Toulouse, France. [Vermassen, Frank] Ghent Univ Hosp, Dept Vasc Surg, Ghent, Belgium. [Popma, Jeffrey J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [McGreevy, Robert; Rapoza, Richard; Schwartz, Lewis B.] Abbott Vasc, Santa Clara, CA USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ultrasound Core Lab, Boston, MA 02114 USA. RP Lammer, J (reprint author), Med Univ Vienna, Waehringer Guertel 18, A-1090 Vienna, Austria. EM jlammer@gmx.at FU Abbott Vascular FX The study was supported and monitored by Abbott Vascular. Drs. Lammer, Bosiers, Zeller, Scheinert, and Vermassen are members of Abbott Vascular scientific advisory board. Dr. Lammer received honorarium as principal investigator of the ESPRIT I study. Dr. Schmidt consults for Abbott Vascular. Dr. Popma has received grants from Abbott Vascular. Drs. McGreevy and Rapoza are employees of Abbott Vascular. Dr. Schwartz is a former employee of Abbott Vascular. Dr. Jaff is a uncompensated advisor to Abbott Vascular; a board member of VIVA Physicians; and an equity shareholder in PQ Bypass. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 27 TC 3 Z9 3 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 EI 1876-7605 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD JUN 13 PY 2016 VL 9 IS 11 BP 1178 EP 1187 DI 10.1016/j.jcin.2016.02.051 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DN9SF UT WOS:000377419700019 PM 27282601 ER PT J AU Pan, JB Liu, S Farkas, M Consugar, M Zack, DJ Kozak, I Arevalo, JF Pierce, E Qian, J Al Kahtani, E AF Pan, Jianbo Liu, Sheng Farkas, Michael Consugar, Mark Zack, Donald J. Kozak, Igor Arevalo, J. Fernando Pierce, Eric Qian, Jiang Al Kahtani, Eman TI Serum molecular signature for proliferative diabetic retinopathy in Saudi patients with type 2 diabetes SO MOLECULAR VISION LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RNA-SEQ EXPERIMENTS; RISK-FACTORS; CARDIOVASCULAR-DISEASE; CONNECTIVITY MAP; VEGF RECEPTORS; EYE DISEASE; EXPRESSION; BIOMARKERS; GENE AB Purpose: The risk of vision loss from proliferative diabetic retinopathy (PDR) can be reduced with timely detection and treatment. We aimed to identify serum molecular signatures that might help in the early detection of PDR in patients with diabetes. Methods: A total of 40 patients with diabetes were recruited at King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia, 20 with extensive PDR and 20 with mild non-proliferative diabetic retinopathy (NPDR). The two groups were matched in age, gender, and known duration of diabetes. We examined the whole genome transcriptome of blood samples from the patients using RNA sequencing. We built a model using a support vector machine (SVM) approach to identify gene combinations that can classify the two groups. Results: Differentially expressed genes were calculated from a total of 25,500 genes. Six genes (CCDC144NL, DYX1C1, KCNH3, LOC100506476, LOC285847, and ZNF80) were selected from the top 26 differentially expressed genes, and a combinatorial molecular signature was built based on the expression of the six genes. The mean area under receiver operating characteristic (ROC) curve was 0.978 in the cross validation. The corresponding sensitivity and specificity were 91.7% and 91.5%, respectively. Conclusions: Our preliminary study defined a combinatorial molecular signature that may be useful as a potential biomarker for early detection of proliferative diabetic retinopathy in patients with diabetes. A larger-scale study with an independent cohort of samples is necessary to validate and expand these findings. C1 [Pan, Jianbo; Liu, Sheng; Zack, Donald J.; Arevalo, J. Fernando; Qian, Jiang] Johns Hopkins Sch Med, Dept Ophthalmol, Baltimore, MD USA. [Farkas, Michael; Consugar, Mark; Pierce, Eric] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Genom Inst, Boston, MA USA. [Farkas, Michael; Consugar, Mark; Pierce, Eric] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat,Dept Opht, Boston, MA USA. [Kozak, Igor; Arevalo, J. Fernando; Al Kahtani, Eman] King Khalid Eye Specialist Hosp, Vitreoretina Div, Riyadh 11462, Saudi Arabia. [Qian, Jiang] Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Al Kahtani, E (reprint author), King Khalid Eye Specialist Hosp, Vitreoretina Div, Riyadh 11462, Saudi Arabia. EM ekahtani@kkesh.med.sa FU KKESH hospital [KKESHJHU01-02] FX The study was supported by a grant from KKESH hospital (KKESHJHU01-02). We thank Dr. Zhen Zhang for the discussion. The authors declare that there are no conflicts of interest. Jiang Qian, Ph.D. (jiang.qian@jhmi.edu) and Eman Al Kahtani, MD (ekahtani@kkesh.med.sa) are co-corresponding authors on this manuscript. NR 39 TC 0 Z9 0 U1 0 U2 0 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD JUN 11 PY 2016 VL 22 BP 636 EP 645 PG 10 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA DO6YY UT WOS:000377930600001 PM 27307695 ER PT J AU Singh, JA Schleck, C Harmsen, S Lewallen, D AF Singh, Jasvinder A. Schleck, Cathy Harmsen, Scott Lewallen, David TI Clinically important improvement thresholds for Harris Hip Score and its ability to predict revision risk after primary total hip arthroplasty SO BMC MUSCULOSKELETAL DISORDERS LA English DT Article DE Harris Hip Score; Total Hip Arthroplasty; Responsiveness; Discriminant ability; Predictability; Clinically important improvement; Minimal clinically important improvement; MCII; Minimal clinically important difference; MCID ID RESPONSIVENESS; REPLACEMENT; TRIALS; KNEE; PAIN; OSTEOARTHRITIS; FRACTURES; MORTALITY; ARTHRITIS; TRENDS AB Background: Some aspects of validity are missing for the Harris Hip Score (HHS). Our objective was to examine the clinically meaningful change thresholds, responsiveness and the predictive ability of the HHS questionnaire. Methods: We included a cohort of patients who underwent primary total hip arthroplasty (THA) and responded to the HHS preoperatively and at 2- or 5-year post-THA (change score) to examine the clinically meaningful change thresholds (Minimal clinically important improvement, MCII; and moderate improvement), responsiveness (effect size (ES) and standardized response mean (SRM)) based on pre- to post-operative change and the predictive ability of change score or absolute postoperative score at 2- and 5-years post-THA for future revision. Results: Two thousand six hundred sixty-seven patients with a mean age of 64 years completed baseline HHS; 1036 completed both baseline and 2-year HHS and 669 both baseline and 5-year HHS. MCII and moderate improvement thresholds ranged 15.9-18 points and 39.6-40.1 points, respectively. ES was 3.12 and 3.02 at 2- and 5-years; respective SRM was 2.73 and 2.52. There were 3195 hips with HHS scores at 2-years and 2699 hips with HHS scores at 5-years (regardless of the completion of baseline HHS; absolute postoperative scores). Compared to patients with absolute HHS scores of 81-100 (score range, 0-100), patients with scores <55 at 2- and 5-years had higher hazards (95 % confidence interval) of subsequent revision, 4.34 (2.14, 7.95; p < 0.001) and 3.08 (1.45, 5.84; p = 0.002), respectively. Compared to HHS score improvement of >50 points from preoperative to 2-years post-THA, lack of improvement/worsening or 1-20 point improvement were associated with increased hazards of revision, 18.10 (1.41, 234.83; p = 0.02); and 6.21 (0.81, 60.73; p = 0.10), respectively. Conclusions: HHS is a valid measure of THA outcomes and is responsive to change. Both absolute HHS postoperative scores and HHS score change postoperatively are predictive of revision risk post-primary THA. We defined MCID and moderate improvement thresholds for HHS in this study. C1 [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham VA Med Ctr, Med Serv, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Orthoped Surg, Rochester, MN USA. [Schleck, Cathy; Harmsen, Scott] Mayo Clin, Sch Med, Dept Biostat, Rochester, MN USA. [Singh, Jasvinder A.; Lewallen, David] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Birmingham VA Med Ctr, Med Serv, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA.; Singh, JA (reprint author), Mayo Clin, Sch Med, Dept Orthoped Surg, Rochester, MN USA.; Singh, JA (reprint author), Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA.; Singh, JA (reprint author), Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com FU Department of Orthopedic Surgery at Mayo Clinic FX The funding source, Department of Orthopedic Surgery at Mayo Clinic, played no role in protocol development, study conduct, interpretation of results, or the decision to submit the manuscript for publication. NR 27 TC 3 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2474 J9 BMC MUSCULOSKEL DIS JI BMC Musculoskelet. Disord. PD JUN 10 PY 2016 VL 17 AR 256 DI 10.1186/s12891-016-1106-8 PG 8 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA DP0TN UT WOS:000378202600001 PM 27286675 ER PT J AU Wareham, LK Begg, R Jesse, HE van Beilen, JWA Ali, S Svistunenko, D McLean, S Hellingwerf, KJ Sanguinetti, G Poole, RK AF Wareham, Lauren K. Begg, Ronald Jesse, Helen E. van Beilen, Johan W. A. Ali, Salar Svistunenko, Dimitri McLean, Samantha Hellingwerf, Klaas J. Sanguinetti, Guido Poole, Robert K. TI Carbon Monoxide Gas Is Not Inert, but Global, in Its Consequences for Bacterial Gene Expression, Iron Acquisition, and Antibiotic Resistance SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID UPTAKE REGULATION PROTEIN; BD QUINOL OXIDASE; ESCHERICHIA-COLI; ELECTRON-TRANSPORT; NITRIC-OXIDE; IN-VIVO; ANTIMICROBIAL AGENTS; REGULATORY PROTEINS; OXYGEN-AFFINITY; CYDAB OPERON AB Aims: Carbon monoxide is a respiratory poison and gaseous signaling molecule. Although CO-releasing molecules (CORMs) deliver CO with temporal and spatial specificity in mammals, and are proven antimicrobial agents, we do not understand the modes of CO toxicity. Our aim was to explore the impact of CO gas per se, without intervention of CORMs, on bacterial physiology and gene expression. Results: We used tightly controlled chemostat conditions and integrated transcriptomic datasets with statistical modeling to reveal the global effects of CO. CO is known to inhibit bacterial respiration, and we found expression of genes encoding energy-transducing pathways to be significantly affected via the global regulators, Fnr, Arc, and PdhR. Aerobically, ArcA-the response regulator-is transiently phosphorylated and pyruvate accumulates, mimicking anaerobiosis. Genes implicated in iron acquisition, and the metabolism of sulfur amino acids and arginine, are all perturbed. The global iron-related changes, confirmed by modulation of activity of the transcription factor Fur, may underlie enhanced siderophore excretion, diminished intracellular iron pools, and the sensitivity of CO-challenged bacteria to metal chelators. Although CO gas (unlike H2S and NO) offers little protection from antibiotics, a ruthenium CORM is a potent adjuvant of antibiotic activity. Innovation: This is the first detailed exploration of global bacterial responses to CO, revealing unexpected targets with implications for employing CORMs therapeutically. Conclusion: This work reveals the complexity of bacterial responses to CO and provides a basis for understanding the impacts of CO from CORMs, heme oxygenase activity, or environmental sources. C1 [Wareham, Lauren K.; Jesse, Helen E.; Ali, Salar; McLean, Samantha; Poole, Robert K.] Univ Sheffield, Dept Mol Biol & Biotechnol, Sheffield S10 2TN, S Yorkshire, England. [Begg, Ronald; Sanguinetti, Guido] Univ Edinburgh, Sch Informat, Edinburgh, Midlothian, Scotland. [van Beilen, Johan W. A.; Hellingwerf, Klaas J.] Univ Amsterdam, Mol Microbial Physiol, Swammerdam Inst Life Sci, Amsterdam, Netherlands. [Svistunenko, Dimitri] Univ Essex, Biomed EPR Facil, Sch Biol Sci, Colchester CO4 3SQ, Essex, England. [Wareham, Lauren K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [McLean, Samantha] Nottingham Trent Univ, Sch Sci & Technol, Nottingham, England. RP Poole, RK (reprint author), Univ Sheffield, Dept Mol Biol & Biotechnol, Sheffield S10 2TN, S Yorkshire, England. EM r.poole@sheffield.ac.uk OI Svistunenko, Dimitri/0000-0001-8060-2738 FU Biotechnology and Biological Sciences Research Council (UK, BBSRC); Kurdistan Regional Government (KRG, Iraq); European Research Council [MLCS306999] FX This work was supported, in part, by the Biotechnology and Biological Sciences Research Council (UK, BBSRC) and the Kurdistan Regional Government (KRG, Iraq). G.S. acknowledges support from the European Research Council under grant MLCS306999. NR 75 TC 1 Z9 1 U1 13 U2 28 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JUN 10 PY 2016 VL 24 IS 17 BP 1013 EP 1028 DI 10.1089/ars.2015.6501 PG 16 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA DO8PO UT WOS:000378045800004 PM 26907100 ER PT J AU Schwartz, KR Fredricks, K Al Tawil, Z Kandler, T Odenyo, SA Imbamba, J Nelson, BD Burke, TF AF Schwartz, Kevin R. Fredricks, Karla Al Tawil, Zaid Kandler, Taylor Odenyo, Stella A. Imbamba, Javan Nelson, Brett D. Burke, Thomas F. TI An innovative safe anesthesia and analgesia package for emergency pediatric procedures and surgeries when no anesthetist is available SO INTERNATIONAL JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE Ketamine; Pediatric analgesia; Anesthesia; Low-income; Resource-limited; Sub-Saharan Africa; Non-anesthetist ID DEVELOPING-COUNTRIES; ADVERSE EVENTS; SEDATION; KETAMINE; CHILDREN; SETTINGS; SERVICES; AFRICA AB Background: Adequate pain control through sedation and anesthesia for emergency procedures is a crucial aspect of pediatric emergency care. Resources for administering such anesthesia are extremely limited in many low-income settings. Methods: Non-anesthetist providers in Western Kenya were trained in the use of a ketamine-based sedation and anesthesia package for non-anesthetists, Every Second Matters for Mothers and Babies-Ketamine T (ESM-Ketamine). Data on use and safety of this package for emergent and urgent pediatric procedures was collected. Providers were surveyed as to what they would have done for similar procedures if the ESM-Ketamine package were unavailable. Results: Ninety procedures were completed for 77 pediatric patients utilizing the ESM-Ketamine package. Of these, 29 (32.2 %) cases were orthopedic reductions, 19 (21.1 %) were incision and drainage, and 19 (21.1 %) were debridement and irrigation of burns. Remaining cases included cesarean section, repair of perineal tear, foreign body removal, arthrocentesis, laceration repair, exploratory laparotomy, excision of mass, paracentesis, and circumcision. There were no serious adverse events in any of the cases, 17 % experienced minor adverse events including hypersalivation, hallucinations, or brief, self-resolving, oxygen desaturations. Providers were surveyed for 80 of the 90 cases as to what they would have done in the absence of the ESM-Ketamine package: in 26 cases (32.5 %), they reported they would proceed with the procedure without any anesthesia or analgesia; in 15 (18.75 %), they reported they would significantly delay the procedure while waiting for an anesthetist; in 13 (16.25 %), they reported they would attempt referral to another facility; and in 26 (32.5 %), they reported they would try using an alternate form of analgesia, primarily acetaminophen, ibuprofen, diclofenac, and/or diazepam. All surveyed providers reported they would use the ESM-Ketamine package again in similar cases. Conclusions: The ESM-Ketamine package, through the use of a simplified protocol and checklist, allows for safe analgesia and anesthesia in children by non-anesthetists in a resource-limited setting for selected emergent and urgent procedures. This package addresses a significant gap in the availability of anesthesia services in low-income settings that would otherwise result in significant delays to procedures or proceeding with painful procedures with inadequate analgesia. C1 [Schwartz, Kevin R.; Fredricks, Karla; Al Tawil, Zaid; Kandler, Taylor; Nelson, Brett D.; Burke, Thomas F.] Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, 125 Nashua St,Suite 910, Boston, MA 02114 USA. [Schwartz, Kevin R.; Nelson, Brett D.; Burke, Thomas F.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Odenyo, Stella A.; Imbamba, Javan] Sagam Community Hosp, African Inst Hlth Transformat, Luanda, Kenya. RP Schwartz, KR (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, 125 Nashua St,Suite 910, Boston, MA 02114 USA.; Schwartz, KR (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM krschwartz@mgh.harvard.edu OI Nelson, Brett/0000-0002-5049-1798 NR 22 TC 1 Z9 1 U1 1 U2 14 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 1865-1372 EI 1865-1380 J9 INT J EMERG MED JI Int. J. Emergency Medicine PD JUN 10 PY 2016 VL 9 AR 16 DI 10.1186/s12245-016-0113-8 PG 7 WC Emergency Medicine SC Emergency Medicine GA DO7EF UT WOS:000377944500001 PM 27286891 ER PT J AU Tagscherer, KE Fassl, A Sinkovic, T Richter, J Schecher, S Macher-Goeppinger, S Roth, W AF Tagscherer, Katrin E. Fassl, Anne Sinkovic, Tabea Richter, Jutta Schecher, Sabrina Macher-Goeppinger, Stephan Roth, Wilfried TI MicroRNA-210 induces apoptosis in colorectal cancer via induction of reactive oxygen SO CANCER CELL INTERNATIONAL LA English DT Article DE miR-210; Colorectal carcinoma; ROS; Bim; Apoptosis ID CELL LUNG-CANCER; BREAST-CANCER; OXIDATIVE STRESS; CASPASE-2 ACTIVATION; PROGNOSTIC-FACTOR; STEM-CELLS; HYPOXIA; EXPRESSION; MIR-210; BCL-2 AB Background: Deregulation of miRNA-210 is a common event in several types of cancer. However, increased expression levels in the cancer tissue have been associated with both poor and good prognosis of patients. Similarly, the function of miR-210 with regard to cell growth and apoptosis is still controversial. Methods: Overexpression of miR-210 was performed in HCT116, SW480 and SW707 colorectal cancer (CRC) cell lines. Functional effects of a modulated miR-210 expression were analyzed with regard to proliferation, clonogenicity, cell cycle distribution, reactive oxygen species (ROS) generation, and apoptosis. Furthermore, quantitative real time (RT)-PCR and immunoblot analyses were performed to investigate signaling pathways affected by miR-210. Results: We show that in CRC cells miR-210 inhibits clonogenicity and proliferation which was accompanied by an accumulation of cells in the G2/M phase of the cell cycle. Additionally, overexpression of miR-210 results in an increase of ROS generation. Moreover, miR-210 mediated the induction of apoptosis which was associated with an upregulation of pro-apoptotic Bim expression and enhanced processing of Caspase 2. Importantly, inhibition of ROS generation rescued cells from miR-210-induced apoptosis. Conclusions: Taken together, miR-210 induces apoptosis in CRC cells via a ROS-dependent mechanism. C1 [Tagscherer, Katrin E.; Richter, Jutta; Schecher, Sabrina; Macher-Goeppinger, Stephan; Roth, Wilfried] Univ Med Ctr Mainz, Inst Pathol, Langenbeckstr 1, D-55131 Mainz, Germany. [Tagscherer, Katrin E.; Fassl, Anne; Sinkovic, Tabea; Richter, Jutta; Schecher, Sabrina; Macher-Goeppinger, Stephan; Roth, Wilfried] German Canc Res Ctr, Mol Tumor Pathol, D-69120 Heidelberg, Germany. [Tagscherer, Katrin E.; Fassl, Anne; Sinkovic, Tabea; Richter, Jutta; Schecher, Sabrina; Macher-Goeppinger, Stephan; Roth, Wilfried] Heidelberg Univ, Inst Pathol, D-69120 Heidelberg, Germany. [Fassl, Anne] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Fassl, Anne] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA. RP Tagscherer, KE (reprint author), Univ Med Ctr Mainz, Inst Pathol, Langenbeckstr 1, D-55131 Mainz, Germany.; Tagscherer, KE (reprint author), German Canc Res Ctr, Mol Tumor Pathol, D-69120 Heidelberg, Germany.; Tagscherer, KE (reprint author), Heidelberg Univ, Inst Pathol, D-69120 Heidelberg, Germany. EM Katrin.Tagscherer@unimedizin-mainz.de FU German Research Foundation (DFG) [RO2270/6-1] FX We thank Stefan Herzig (DKFZ, Heidelberg) for kindly providing recombinant adenoviruses, and Martina Keith for excellent technical assistance. We further thank all laboratory members for helpful suggestions and discussions. This study was supported by the German Research Foundation (DFG; #RO2270/6-1). NR 73 TC 3 Z9 3 U1 5 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2867 J9 CANCER CELL INT JI Cancer Cell Int. PD JUN 10 PY 2016 VL 16 AR 42 DI 10.1186/s12935-016-0321-6 PG 12 WC Oncology SC Oncology GA DO1KT UT WOS:000377537600001 PM 27293381 ER PT J AU Chatzipanagiotou, S Ioannidis, A Trikka-Graphakos, E Charalampaki, N Sereti, C Piccinini, R Higgins, AM Buranda, T Durvasula, R Hoogesteijn, AL Tegos, GP Rivas, AL AF Chatzipanagiotou, S. Ioannidis, A. Trikka-Graphakos, E. Charalampaki, N. Sereti, C. Piccinini, R. Higgins, A. M. Buranda, T. Durvasula, R. Hoogesteijn, A. L. Tegos, G. P. Rivas, Ariel L. TI Detecting the Hidden Properties of Immunological Data and Predicting the Mortality Risks of Infectious Syndromes SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE complexity; immunomicrobial interactions; sepsis; immunosuppression; pattern recognition; visual ID PERSONALIZED MEDICINE; SYSTEMS BIOLOGY; SEPSIS; COMPLEXITY; CHALLENGES; EMERGENCE; SCIENCE; DISEASE; FUTURE; IMMUNOSUPPRESSION AB Background: To extract more information, the properties of infectious disease data, including hidden relationships, could be considered. Here, blood leukocyte data were explored to elucidate whether hidden information, if uncovered, could forecast mortality. Methods: Three sets of individuals (n = 132) were investigated, from whom blood leukocyte profiles and microbial tests were conducted (i) cross-sectional analyses performed at admission (before bacteriological tests were completed) from two groups of hospital patients, randomly selected at different time periods, who met septic criteria [confirmed infection and at least three systemic inflammatory response syndrome (SIRS) criteria] but lacked chronic conditions (study I, n = 36; and study II, n = 69); (ii) a similar group, tested over 3 days (n = 7); and (iii) non-infected, SIRS-negative individuals, tested once (n = 20). The data were analyzed by (i) a method that creates complex data combinations, which, based on graphic patterns, partitions the data into subsets and (ii) an approach that does not partition the data. Admission data from SIRS+/infection+ patients were related to 30-day, in-hospital mortality. Results: The non-partitioning approach was not informative: in both study I and study II, the leukocyte data intervals of non-survivors and survivors overlapped. In contrast, the combinatorial method distinguished two subsets that, later, showed twofold (or larger) differences in mortality. While the two subsets did not differ in gender, age, microbial species, or antimicrobial resistance, they revealed different immune profiles. Non-infected, SIRS-negative individuals did not express the high mortality profile. Longitudinal data from septic patients displayed the pattern associated with the highest mortality within the first 24 h post-admission. Suggesting inflammation coexisted with immunosuppression, one high-mortality sub-subset displayed high neutrophil/ lymphocyte ratio values and low lymphocyte percents. A second high-mortality subset showed monocyte-mediated deficiencies. Numerous within- and between-subset comparisons revealed statistically significantly different immune profiles. Conclusion: While the analysis of non-partitioned data can result in information loss, complex (combinatorial) data structures can uncover hidden patterns, which guide data partitioning into subsets that differ in mortality rates and immune profiles. Such information can facilitate diagnostics, monitoring of disease dynamics, and evaluation of subset-specific, patient-specific therapies. C1 [Chatzipanagiotou, S.] Univ Athens, Sch Med, Aeginit Hosp, Dept Biopathol & Clin Microbiol, Athens 11528, Greece. [Ioannidis, A.] Univ Peloponnese, Fac Human Movement & Qual Life Sci, Dept Nursing, Sparta, Greece. [Trikka-Graphakos, E.; Charalampaki, N.; Sereti, C.] Thriasio Gen Hosp, Dept Clin Microbiol, Magoula, Greece. [Piccinini, R.] Univ Milan, Dept Vet Sci & Publ Hlth, Milan, Italy. [Higgins, A. M.; Durvasula, R.; Rivas, Ariel L.] Univ New Mexico, Sch Med, Div Infect Dis, Ctr Global Hlth, Albuquerque, NM 87131 USA. [Buranda, T.] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA. [Hoogesteijn, A. L.] CINVESTAV, Dept Human Ecol, Unidad Merida, Mexico City, DF, Mexico. [Tegos, G. P.] Torrey Pines Inst Mol Studies, Port St Lucie, FL USA. [Tegos, G. P.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Tegos, G. P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Rivas, AL (reprint author), Univ New Mexico, Sch Med, Div Infect Dis, Ctr Global Hlth, Albuquerque, NM 87131 USA. EM alrivas@unm.edu NR 69 TC 0 Z9 0 U1 1 U2 1 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PD JUN 10 PY 2016 VL 7 AR 217 DI 10.3389/fimmu.2016.00217 PG 14 WC Immunology SC Immunology GA DO1BH UT WOS:000377512800001 PM 27375617 ER PT J AU Szaflarski, JP Lee, S Allendorfer, JB Gaston, TE Knowlton, RC Pati, S Ver Hoef, LW Deutsch, G AF Szaflarski, Jerzy P. Lee, Seongtaek Allendorfer, Jane B. Gaston, Tyler E. Knowlton, Robert C. Pati, Sandipan Ver Hoef, Lawrence W. Deutsch, Georg TI White Matter Abnormalities in Patients with Treatment-Resistant Genetic Generalized Epilepsies SO MEDICAL SCIENCE MONITOR LA English DT Article DE Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Epilepsy, Absence; Myoclonic Epilepsy, Juvenile ID JUVENILE MYOCLONIC EPILEPSY; TEMPORAL-LOBE EPILEPSY; LANGUAGE LATERALIZATION; FUNCTIONAL CONNECTIVITY; EPILEPTIFORM DISCHARGES; STRUCTURAL-CHANGES; WAVE DISCHARGE; SEIZURES; NETWORK; EEG AB Background: Genetic generalized epilepsies (GGEs) are associated with microstructural brain abnormalities that can be evaluated with diffusion tensor imaging (DTI). Available studies on GGEs have conflicting results. Our primary goal was to compare the white matter structure in a cohort of patients with video/EEG-confirmed GGEs to healthy controls (HCs). Our secondary goal was to assess the potential effect of age at GGE onset on the white matter structure. Material/Methods: A convenience sample of 23 patients with well-characterized treatment-resistant GGEs (13 female) was compared to 23 HCs. All participants received MRI at 3T. DTI indices, including fractional anisotropy (FA) and mean diffusivity (MD), were compared between groups using Tract-Based Spatial Statistics (TBSS). Results: After controlling for differences between groups, abnormalities in DTI parameters were observed in patients with GGEs, including decreases in functional anisotropy (FA) in the hemispheric (left>right) and brain stem white matter. The examination of the effect of age at GGE onset on the white matter integrity revealed a significant negative correlation in the left parietal white matter region FA (R=-0.504; p=0.017); similar trends were observed in the white matter underlying left motor cortex (R=-0.357; p=0.103) and left posterior limb of the internal capsule (R=-0.319; p=0.148). Conclusions: Our study confirms the presence of widespread white matter abnormalities in patients with GGEs and provides evidence that the age at GGE onset may have an important effect on white matter integrity. C1 [Szaflarski, Jerzy P.; Allendorfer, Jane B.; Gaston, Tyler E.; Knowlton, Robert C.; Pati, Sandipan; Ver Hoef, Lawrence W.] Univ Alabama Birmingham, Dept Neurol, UAB Stn, Birmingham, AL 35294 USA. [Szaflarski, Jerzy P.] Univ Alabama Birmingham, Dept Neurobiol, Birmingham, AL USA. [Szaflarski, Jerzy P.; Lee, Seongtaek] Univ Alabama Birmingham, Dept Biomed Engn, Birmingham, AL 35294 USA. [Gaston, Tyler E.; Ver Hoef, Lawrence W.] Birmingham VAMC, Dept Neurol, Birmingham, AL USA. [Knowlton, Robert C.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Deutsch, Georg] Univ Alabama Birmingham, Dept Radiol, Birmingham, AL USA. RP Szaflarski, JP (reprint author), Univ Alabama Birmingham, Dept Neurol, UAB Stn, Birmingham, AL 35294 USA.; Szaflarski, JP (reprint author), Univ Alabama Birmingham, Dept Neurobiol, Birmingham, AL USA.; Szaflarski, JP (reprint author), Univ Alabama Birmingham, Dept Biomed Engn, Birmingham, AL 35294 USA. EM szaflaj@uab.edu OI Lee, Seongtaek/0000-0001-8954-6103 NR 53 TC 1 Z9 1 U1 2 U2 4 PU INT SCIENTIFIC LITERATURE, INC PI SMITHTOWN PA 361 FOREST LANE, SMITHTOWN, NY 11787 USA SN 1643-3750 J9 MED SCI MONITOR JI Med. Sci. Monitor PD JUN 10 PY 2016 VL 22 BP 1966 EP 1975 DI 10.12659/MSM.897002 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DO2RY UT WOS:000377628900001 PM 27283395 ER PT J AU Mullane, SA Werner, L Rosenberg, J Signoretti, S Callea, M Choueiri, TK Freeman, GJ Bellmunt, J AF Mullane, Stephanie A. Werner, Lillian Rosenberg, Jonathan Signoretti, Sabina Callea, Marcella Choueiri, Toni K. Freeman, Gordon J. Bellmunt, Joaquim TI Correlation of Apobec Mrna Expression with overall Survival and pd-l1 Expression in Urothelial Carcinoma SO SCIENTIFIC REPORTS LA English DT Article ID INVASIVE BLADDER-CANCER; RENAL-CELL CARCINOMA; MUTATIONAL SIGNATURES; GENOMIC INSTABILITY; CYTIDINE DEAMINASES; BREAST-CANCER; DNA; BLOCKADE; HIV-1; HYPERMUTATION AB Metastatic urothelial carcinoma (mUC) has a very high mutational rate and is associated with an APOBEC mutation signature. We examined the correlation of APOBEC expression with overall survival (OS) and PD-L1 expression in a cohort of 73 mUC patients. mRNA expression of APOBEC3 family of genes (A3A, A3B, A3C, A3F_a, A3F_b, A3G, A3H) was measured using Nanostring. PD-L1 expression, evaluated by immunohistochemistry, on tumor infiltrating mononuclear cells (TIMCs) and tumor cells was scored from 0 to 4, with 2-4 being positive. Wilcoxon's non-parametric tests assessed the association of APOBEC and PD-L1. The Cox regression model assessed the association of APOBEC with OS. All APOBEC genes were expressed in mUC. Increased A3A, A3D, and A3H expression associates with PD-L1 positive TIMCs (p = 0.0009, 0.009, 0.06). Decreased A3B expression was marginally associated with PD-L1 positive TIMCs expression (p = 0.05). Increased A3F_a and A3F_b expression was associated with increased expression of PD-L1 on tumor cells (p = 0.05). Increased expression of A3D and A3H was associated with longer OS (p = 0.0009). Specific APOBEC genes have different effects on mUC in terms of survival and PD-L1 expression. A3D and A3H may have the most important role in mUC as they are associated with OS and PD-L1 TIMC expression. C1 [Mullane, Stephanie A.; Werner, Lillian; Signoretti, Sabina; Choueiri, Toni K.; Bellmunt, Joaquim] Brigham & Womens Hosp, Dana Farber Canc Inst, Bladder Canc Ctr, 75 Francis St, Boston, MA 02115 USA. [Werner, Lillian] Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02115 USA. [Rosenberg, Jonathan] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Signoretti, Sabina; Callea, Marcella] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Signoretti, Sabina; Choueiri, Toni K.; Freeman, Gordon J.; Bellmunt, Joaquim] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Choueiri, Toni K.; Freeman, Gordon J.; Bellmunt, Joaquim] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bellmunt, Joaquim] Univ Hosp Mar IMIM, Barcelona, Spain. RP Bellmunt, J (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Bladder Canc Ctr, 75 Francis St, Boston, MA 02115 USA.; Bellmunt, J (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.; Bellmunt, J (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.; Bellmunt, J (reprint author), Univ Hosp Mar IMIM, Barcelona, Spain. EM joaquim_bellmunt@dfci.harvard.edu FU Spanish Health Ministry Grant "Fondo de Investigacion Sanitaria" [FIS PI10/02112]; Retired Professional Fire Fighters Cancer Fund; Whole Foods Golf Classic for bladder cancer research in memoriam of Christopher Snell; Friends of Dana-Farber; Pla Director d'Oncologia de Catalunya (XBTC); [RTICC 06/0020/19] FX This work has been supported by FIS PI10/02112 (microRNAS) (Spanish Health Ministry Grant "Fondo de Investigacion Sanitaria") and RTICC 06/0020/19 grants. Fundacio Cellex (Barcelona) provided a generous donation to the Group of Molecular Therapeutics and Biomarkers, Hospital del Mar. The Tumor Bank of the Department of Pathology of Hospital del Mar (RD09/0076/0036) and the Xarxa de Bancs de Tumors sponsored by Pla Director d'Oncologia de Catalunya (XBTC) provided tissue samples. This study was also possible thanks to a grant from Friends of Dana-Farber, the Retired Professional Fire Fighters Cancer Fund, and the generous support of Whole Foods Golf Classic for bladder cancer research in memoriam of Christopher Snell. Also a private donation in the memory of Rich Beaudoin. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 5 Z9 5 U1 0 U2 1 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 JUN 10 PY 2016 VL 6 AR 27702 DI 10.1038/srep27702 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DO3OM UT WOS:000377690900001 PM 27283319 ER PT J AU Press, OW Li, HL Schoder, H Straus, DJ Moskowitz, CH LeBlanc, M Rimsza, LM Bartlett, NL Evens, AM Mittra, ES LaCasce, AS Sweetenham, JW Barr, PM Fanale, MA Knopp, MV Noy, A Hsi, ED Cook, JR Lechowicz, MJ Gascoyne, RD Leonard, JP Kahl, BS Cheson, BD Fisher, RI Friedberg, JW AF Press, Oliver W. Li, Hongli Schoder, Heiko Straus, David J. Moskowitz, Craig H. LeBlanc, Michael Rimsza, Lisa M. Bartlett, Nancy L. Evens, Andrew M. Mittra, Erik S. LaCasce, Ann S. Sweetenham, John W. Barr, Paul M. Fanale, Michelle A. Knopp, Michael V. Noy, Ariela Hsi, Eric D. Cook, James R. Lechowicz, Mary Jo Gascoyne, Randy D. Leonard, John P. Kahl, Brad S. Cheson, Bruce D. Fisher, Richard I. Friedberg, Jonathan W. TI US Intergroup Trial of Response-Adapted Therapy for Stage III to IV Hodgkin Lymphoma Using Early Interim Fluorodeoxyglucose-Positron Emission Tomography Imaging: Southwest Oncology Group S0816 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INTERNATIONAL PROGNOSTIC SCORE; CLINICAL-TRIALS; FDG-PET; ABVD; CHEMOTHERAPY; SURVIVAL; BEACOPP; DISEASE; RADIOTHERAPY; INTENSITY AB Purpose Four US National Clinical Trials Network components (Southwest Oncology Group, Cancer and Leukemia Group B/Alliance, Eastern Cooperative Oncology Group, and the AIDS Malignancy Consortium) conducted a phase II Intergroup clinical trial that used early interim fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to determine the utility of response-adapted therapy for stage III to IV classic Hodgkin lymphoma. Patients and Methods The Southwest Oncology Group S0816 (Fludeoxyglucose F 18-PET/CT Imaging and Combination Chemotherapy With or Without Additional Chemotherapy and G-CSF in Treating Patients With Stage III or Stage IV Hodgkin Lymphoma) trial enrolled 358 HIV-negative patients between July 1, 2009, and December 2, 2012. A PET scan was performed after two initial cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and was labeled PET2. PET2-negative patients (Deauville score 1 to 3) received an additional four cycles of ABVD, whereas PET2-positive patients (Deauville score 4 to 5) were switched to escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) for six cycles. Among 336 eligible and evaluable patients, the median age was 32 years (range, 18 to 60 years), with 52% stage III, 48% stage IV, 49% International Prognostic Score 0 to 2, and 51% score 3 to 7. Results Three hundred thirty-six of the enrolled patients were evaluable. Central review of the interim PET2 scan was performed in 331 evaluable patients, with 271 (82%) PET2-negative and 60 (18%) PET2-positive. Of 60 eligible PET2-positive patients, 49 switched to eBEACOPP as planned and 11 declined. With a median follow-up of 39.7 months, the Kaplan-Meier estimate for 2-year overall survival was 98% (95% CI, 95% to 99%), and the 2-year estimate for progression-free survival (PFS) was 79% (95% CI, 74% to 83%). The 2-year estimate for PFS in the subset of patients who were PET2-positive after two cycles of ABVD was 64% (95% CI, 50% to 75%). Both nonhematologic and hematologic toxicities were greater in the eBEACOPP arm than in the continued ABVD arm. Conclusion Response-adapted therapy based on interim PET imaging after two cycles of ABVD seems promising with a 2-year PFS of 64% for PET2-positive patients, which is much higher than the expected 2-year PFS of 15% to 30%. C1 [Press, Oliver W.; Li, Hongli; LeBlanc, Michael] Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D3-190, Seattle, WA 98109 USA. [Press, Oliver W.] Univ Washington, Seattle, WA 98195 USA. [Schoder, Heiko; Straus, David J.; Moskowitz, Craig H.; Noy, Ariela] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Leonard, John P.] Weill Cornell Med Coll, New York, NY USA. [Leonard, John P.] New York Presbyterian Hosp, New York, NY USA. [Barr, Paul M.; Friedberg, Jonathan W.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Rimsza, Lisa M.] Univ Arizona, Tucson, AZ USA. [Bartlett, Nancy L.; Kahl, Brad S.] Washington Univ, Sch Med, St Louis, MO USA. [Evens, Andrew M.] Tufts Med Ctr, Boston, MA USA. [LaCasce, Ann S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mittra, Erik S.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Sweetenham, John W.] Huntsman Canc Hosp, Salt Lake City, UT USA. [Fanale, Michelle A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Knopp, Michael V.] Ohio State Univ, Columbus, OH 43210 USA. [Hsi, Eric D.] Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA. [Cook, James R.] Cleveland Clin, Cleveland, OH 44106 USA. [Lechowicz, Mary Jo] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Cheson, Bruce D.] Georgetown Univ Hosp, Washington, DC 20007 USA. [Fisher, Richard I.] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. RP Press, OW (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D3-190, Seattle, WA 98109 USA. EM press@u.washington.edu FU Public Health Service, Department of Health and Human Services, National Cancer Institute (NCI), National Clinical Trials Network [CA180888, CA180819, CA180821, CA180820, CA180799, CA180816, CA180801, CA180835, CA180858, CA180846, CA180818, CA180828, CA180826, CA180834]; NCI Community Oncology Research Program [CA189830, CA189971, CA189808, CA189854, CA189821, CA189848, CA189858, CA189860, CA189872, CA189856]; National Institutes of Health (NIH)-NCI [CA31946]; NIH American Recovery and Reinvestment [3U10CA032102-30S1]; NCI AIDS Malignancy Clinical Trials Consortium [CA121947]; David and Patricia Giuliani Family Foundation; Lymphoma Foundation; Adam Spector Fund for Hodgkin's Research; Ernest and Jeanette Dicker Charitable Foundation FX Supported in part by Grants No. CA180888, CA180819, CA180821, CA180820, CA180799, CA180816, CA180801, CA180835, CA180858, CA180801, CA180846, CA180835, CA180818, CA180828, CA180826, and CA180834 from the Public Health Service, Department of Health and Human Services, National Cancer Institute (NCI), National Clinical Trials Network; by Grants No. CA189830, CA189971, CA189808, CA189854, CA189821, CA189848, CA189858, CA189860, CA189872, and CA189856 from the NCI Community Oncology Research Program; by Grant No. CA31946 from the National Institutes of Health (NIH)-NCI; by Grant No. 3U10CA032102-30S1 from the NIH American Recovery and Reinvestment Act of 2009 for the interim FDG-PET imaging; by Grant No. CA121947 from the NCI AIDS Malignancy Clinical Trials Consortium; and by the David and Patricia Giuliani Family Foundation (O.W.P.), The Lymphoma Foundation (D.J.S.), the Adam Spector Fund for Hodgkin's Research (D.J.S.), and the Ernest and Jeanette Dicker Charitable Foundation (D.J.S.). NR 28 TC 25 Z9 25 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 JUN 10 PY 2016 VL 34 IS 17 BP 2020 EP + DI 10.1200/JCO.2015.63.1119 PG 10 WC Oncology SC Oncology GA DN9DC UT WOS:000377378400010 PM 27069074 ER PT J AU Jakubowiak, A Offidani, M Pegourie, B De La Rubia, J Garderet, L Laribi, K Bosi, A Marasca, R Laubach, J Mohrbacher, A Carella, AM Singhal, AK Tsao, LC Lynch, M Bleickardt, E Jou, YM Robbins, M Palumbo, A AF Jakubowiak, Andrzej Offidani, Massimo Pegourie, Brigitte De La Rubia, Javier Garderet, Laurent Laribi, Kamel Bosi, Alberto Marasca, Roberto Laubach, Jacob Mohrbacher, Ann Carella, Angelo Michele Singhal, Anil K. Tsao, L. Claire Lynch, Mark Bleickardt, Eric Jou, Ying-Ming Robbins, Michael Palumbo, Antonio TI Randomized phase 2 study: elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM SO BLOOD LA English DT Article ID REFRACTORY MULTIPLE-MYELOMA; MONOCLONAL-ANTIBODY; DEXAMETHASONE; BORTEZOMIB; COMBINATION; TRIAL; LENALIDOMIDE; CYTOTOXICITY; THERAPY; FUTURE AB In this proof-of-concept, open-label, phase 2 study, patients with relapsed/refractory multiple myeloma (RRMM) received elotuzumab with bortezomib and dexamethasone (EBd) or bortezomib and dexamethasone (Bd) until disease progression/unacceptable toxicity. Primary endpoint was progression-free survival (PFS); secondary/exploratory endpoints included overall response rate (ORR) and overall survival (OS). Two-sided 0.30 significance level was specified (80% power, 103 events) to detect hazard ratio (HR) of 0.69. Efficacy and safety analyses were performed on all randomized patients and all treated patients, respectively. Of 152 randomized patients (77 EBd, 75 Bd), 150 were treated (75 EBd, 75 Bd). PFSwasgreater with EBd vs Bd (HR, 0.72; 70% confidence interval [CI], 0.59-0.88; stratified log-rank P = .09); median PFS was longer with EBd (9.7 months) vs Bd (6.9 months). In an updated analysis, EBd-treated patients homozygous for the high-affinity Fc gamma RIIIa allele had median PFS of 22.3 months vs 9.8 months in EBd-treated patients homozygous for the low-affinity allele. ORR was 66% (EBd) vs 63% (Bd). Very good partial response or better occurred in 36% of patients (EBd) vs 27% (Bd). Early OS results, based on 40 deaths, revealed an HR of 0.61 (70% CI, 0.43-0.85). To date, 60 deaths have occurred (28 EBd, 32 Bd). No additional clinically significant adverse events occurred with EBd vs Bd. Grade 1/2 infusion reaction rate was low (5% EBd) and mitigated with premedication. In patients with RRMM, elotuzumab, an immunostimulatory antibody, appears to provide clinical benefit without added clinically significant toxicity when combined with Bd vs Bd alone. Registered to ClinicalTrials.gov as NCT01478048. C1 [Jakubowiak, Andrzej] Univ Chicago, Med Ctr, Sect Hematol Oncol, Myeloma Program, Chicago, IL 60637 USA. [Offidani, Massimo] Azienda Osped Univ Osped Riuniti Ancona, Clin Ematol, Ancona, Italy. [Pegourie, Brigitte] Ctr Hosp Univ Grenoble, Hop Albert Michallon, Grenoble, France. [De La Rubia, Javier] Hosp Univ Doctor Peset, Valencia, Spain. [De La Rubia, Javier] Univ Catolica San Vicente Martir, Valencia, Spain. [Garderet, Laurent] Hop St Antoine, Serv Hematol, F-75571 Paris, France. [Laribi, Kamel] Ctr Hosp, Dept Hematol, Le Mans, France. [Bosi, Alberto] Azienda Osped Univ Careggi, Dept Hematol, Florence, Italy. [Marasca, Roberto] Azienda Osped Univ Policlin Modena, Dept Hematol, Modena, Italy. [Laubach, Jacob] Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02115 USA. [Mohrbacher, Ann] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Div Hematol, Los Angeles, CA 90033 USA. [Carella, Angelo Michele] Ist Sci Studio & Cura Tumori, Ist Ricovero & Cura Carattere Sci San Martino, Hematol Unit, Genoa, Italy. [Singhal, Anil K.; Tsao, L. Claire] AbbVie Biotherapeut Inc, Stat, Redwood City, CA USA. [Lynch, Mark; Bleickardt, Eric] Bristol Myers Squibb Co, Oncol Clin Dev, 5 Res Pkwy, Wallingford, CT 06492 USA. [Jou, Ying-Ming] Bristol Myers Squibb Co, Global Biometr Sci, Hopewell, NJ USA. [Robbins, Michael] Bristol Myers Squibb Co, Exploratory Clin & Translat Res Oncol, Princeton, NJ USA. [Palumbo, Antonio] Univ Turin, Azienda Osped Univ Citta Salute & Sci Torino, Myeloma Unit, Div Hematol, Turin, Italy. RP Jakubowiak, A (reprint author), Univ Chicago, Med Ctr, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA. EM ajakubowiak@medicine.bsd.uchicago.edu RI Marasca, Roberto/I-8072-2013 OI Marasca, Roberto/0000-0002-6431-6878 FU Bristol-Myers Squibb FX This work was funded by Bristol-Myers Squibb. NR 25 TC 20 Z9 20 U1 3 U2 6 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 JUN 9 PY 2016 VL 127 IS 23 BP 2833 EP 2840 DI 10.1182/blood-2016-01-694604 PG 8 WC Hematology SC Hematology GA DP2QW UT WOS:000378335900014 PM 27091875 ER PT J AU Malarkey, CS Gustafson, CE Saifee, JF Torres, RM Churchill, MEA Janoff, EN AF Malarkey, Christopher S. Gustafson, Claire E. Saifee, Jessica F. Torres, Raul M. Churchill, Mair E. A. Janoff, Edward N. TI Mechanism of Mitochondrial Transcription Factor A Attenuation of CpG-Induced Antibody Production SO PLOS ONE LA English DT Article ID PLASMACYTOID DENDRITIC CELLS; HIGH BINDING-AFFINITY; NF-KAPPA-B; INFLAMMATORY RESPONSES; BACTERIAL-DNA; CIRCULAR-DICHROISM; NUCLEIC-ACIDS; FACTOR-I; ACTIVATION; PROTEIN AB Mitochondrial transcription factor A (TFAM) had previously been shown to act as a damage associated molecular pattern with the ability to enhance CpG-A phosphorothioate oligodeoxynucleotide (ODN)-mediated stimulation of IFN alpha production from human plasmacytoid dendritic cells. Examination of the mechanism by which TFAM might influence CpG ODN mediated innate immune responses revealed that TFAM binds directly, tightly and selectively to the structurally related CpG-A, -B, and -C ODN. TFAM also modulated the ability of the CpG-B or -C to stimulate the production of antibodies from human B cells. TFAM showed a dose-dependent modulation of CpG-B, and -C -induced antibody production from human B cells in vitro, with enhancement of high dose and inhibition of low doses of CpG stimulation. This effect was linked to the ability of TFAM to directly inhibit the binding of CpG ODNs to B cells, in a manner consistent with the relative binding affinities of TFAM for the ODNs. These data suggest that TFAM alters the free concentration of the CpG available to stimulate B cells by sequestering this ODN in a TFAM-CpG complex. Thus, TFAM has the potential to decrease the pathogenic consequences of exposure to natural CpG-like hypomethylated DNA in vivo, as well as such as that found in traumatic injury, infection, autoimmune disease and during pregnancy. C1 [Malarkey, Christopher S.; Saifee, Jessica F.; Churchill, Mair E. A.] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO 80045 USA. [Malarkey, Christopher S.; Saifee, Jessica F.; Churchill, Mair E. A.] Univ Colorado, Sch Med, Program Struct Biol & Biochem, Aurora, CO 80045 USA. [Gustafson, Claire E.; Janoff, Edward N.] Univ Colorado, Sch Med, Mucosal & Vaccine Res Program Colorado MAVRC, Dept Med, Aurora, CO 80045 USA. [Gustafson, Claire E.; Janoff, Edward N.] Univ Colorado, Sch Med, Program Immunol, Aurora, CO 80045 USA. [Gustafson, Claire E.; Janoff, Edward N.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. [Torres, Raul M.] Univ Colorado, Sch Med, Dept Immunol & Microbiol, Aurora, CO 80045 USA. [Malarkey, Christopher S.] Regis Univ, Sch Pharm, Dept Pharmaceut Sci, 3333 Regis Blvd,H-28, Denver, CO 80221 USA. [Gustafson, Claire E.] Stanford Univ, Dept Med, Palo Alto, CA 94304 USA. [Saifee, Jessica F.] 33 Dover Rd, Wellesley, MA 02482 USA. RP Churchill, MEA (reprint author), Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO 80045 USA. EM Mair.Churchill@ucdenver.edu FU University of Colorado Cancer Center Support Grant [P30CA046934]; Veterans Affairs Research Service; Mucosal and Vaccine Research Program Colorado (MAVRC); University of Colorado Cancer Center [P30CA046934]; National Institutes of Health [T32AI052066, R01AI108479, R01GM111902]; American Heart Association [13POST16330009, 11GRNT7380064]; Gerber Foundation FX The University of Colorado Cancer Center Support Grant (P30CA046934) partially supported the usage of core facilities. National Institutes of Health [T32AI052066 to C.E.G., R01AI108479 to E.N.J., R01GM111902 to M.E.A.C.]; American Heart Association [13POST16330009 to C.S.M., 11GRNT7380064 to M.E.A.C.]; Gerber Foundation [to C.E.G.].; We appreciate the ongoing support of the Veterans Affairs Research Service and the Mucosal and Vaccine Research Program Colorado (MAVRC). The University of Colorado Cancer Center Support Grant (P30CA046934) partially supported the usage of core facilities. This work was supported by the National Institutes of Health [T32AI052066 to C.E.G., R01AI108479 to E.N.J., R01GM111902 to M.E.A.C.]; American Heart Association [13POST16330009 to C.S.M., 11GRNT7380064 to M.E.A.C.]; Gerber Foundation [to C.E.G.]. NR 58 TC 0 Z9 0 U1 3 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 9 PY 2016 VL 11 IS 6 AR e0157157 DI 10.1371/journal.pone.0157157 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DO1TW UT WOS:000377563000098 PM 27280778 ER PT J AU Owens, EA Hyun, H Dost, TL Lee, JH Park, G Pham, DH Park, MH Choi, HS Henary, M AF Owens, Eric A. Hyun, Hoon Dost, Tyler L. Lee, Jeong Heon Park, GwangLi Pham, Dang Huan Park, Min Ho Choi, Hak Soo Henary, Maged TI Near-Infrared Illumination of Native Tissues for Image-Guided Surgery SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID FLUOROPHORES; GLAND; TIME; FLUORESCENCE; PERFUSION; AGENTS; TUMORS AB Our initial efforts to prepare tissue-specific near infrared (NIR) fluorescent compounds generated successful correlation between physicochemical, properties and global uptake in major organs after systemic circulation and biodistribution. Herein, we focus on the effects on biodistribution based on modulating electronic influencing moieties from donating to withdrawing moieties at both the heterocyclic site and through meso-substitution of pentamethine cyanine fluorophores. These selected modifications harnessed innate biodistribution pathways through the structure-inherent targeting, resulting in effective imaging of the adrenal glands, pituitary gland, lymph nodes, pancreas, and thyroid and salivary glands. These native-tissue contrast agents will arm surgeons with a powerful and versatile arsenal for intraoperative NIR imaging in real time. C1 [Owens, Eric A.; Dost, Tyler L.; Henary, Maged] Georgia State Univ, Ctr Diagnost & Therapeut, Ctr Biotechnol & Drug Design, Dept Chem,Petit Sci Ctr, 100 Piedmont Ave SE, Atlanta, GA 30303 USA. [Hyun, Hoon; Lee, Jeong Heon; Park, GwangLi; Choi, Hak Soo] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Gordon Ctr Med Imaging, Boston, MA 02114 USA. [Hyun, Hoon; Lee, Jeong Heon; Park, GwangLi; Choi, Hak Soo] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hyun, Hoon; Pham, Dang Huan] Chonnam Natl Univ, Sch Med, Dept Biomed Sci, Gwangju 501746, South Korea. [Hyun, Hoon; Pham, Dang Huan] Chonnam Natl Univ, Sch Med, Dept Surg, Gwangju 501746, South Korea. RP Henary, M (reprint author), Georgia State Univ, Ctr Diagnost & Therapeut, Ctr Biotechnol & Drug Design, Dept Chem,Petit Sci Ctr, 100 Piedmont Ave SE, Atlanta, GA 30303 USA.; Choi, HS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Gordon Ctr Med Imaging, Boston, MA 02114 USA.; Choi, HS (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM hchoi12@mgh.harvard.edu; mhenary1@gsu.edu FU Georgia State University; Brains and Behavior Grant; Health Innovation Grant; Georgia Research Alliance Grant; NIH/NIBIB grant [R01-EB-011523]; Center for Diagnostics and Therapeutics (CDT); Chonnam National University FX This study was supported by a Georgia State University dissertation grant to E.A.O. M.H. wishes to thank the Brains and Behavior Grant, the Health Innovation Grant and the Georgia Research Alliance Grant for their financial support. H.S.C. thanks the NIH/NIBIB grant #R01-EB-011523 for their support. E.A.O. was supported through a predoctoral fellowship from the Center for Diagnostics and Therapeutics (CDT). H.H. was financially supported by Chonnam National University (2015). Thank you Andrew Levitz and Nicholas Bruschi for helping with the synthesis. NR 27 TC 0 Z9 0 U1 6 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD JUN 9 PY 2016 VL 59 IS 11 BP 5311 EP 5323 DI 10.1021/acs.jmedchem.6b00038 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA DO5SG UT WOS:000377842500013 PM 27100476 ER PT J AU Montesi, SB Nance, JW Harris, RS Mark, EJ AF Montesi, Sydney B. Nance, John W. Harris, R. Scott Mark, Eugene J. TI Case 17-2016: A 60-Year-Old Woman with Increasing Dyspnea SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CENTERED INTERSTITIAL FIBROSIS; SURGICAL LUNG BIOPSIES; BRONCHIOLITIS OBLITERANS; FOLLICULAR BRONCHIOLITIS; RHEUMATOID-ARTHRITIS; ALPHA-1-ANTITRYPSIN DEFICIENCY; CONSTRICTIVE BRONCHIOLITIS; DISEASE; INVOLVEMENT; AIRWAYS C1 [Montesi, Sydney B.; Harris, R. Scott] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Nance, John W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Montesi, Sydney B.; Harris, R. Scott] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Nance, John W.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Mark, Eugene J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Montesi, SB (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.; Montesi, SB (reprint author), Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. NR 32 TC 0 Z9 0 U1 1 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 9 PY 2016 VL 374 IS 23 BP 2269 EP 2279 DI 10.1056/NEJMcpc1516452 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA DO6VB UT WOS:000377920500011 PM 27276565 ER PT J AU Greene, MF Drazen, JM AF Greene, Michael F. Drazen, Jeffrey M. TI A New Label for Mifepristone SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MISOPROSTOL C1 [Greene, Michael F.; Drazen, Jeffrey M.] 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 5 TC 1 Z9 1 U1 2 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 9 PY 2016 VL 374 IS 23 BP 2281 EP 2282 DI 10.1056/NEJMe1604462 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DO6VB UT WOS:000377920500012 PM 27276566 ER PT J AU Sequist, LV Soria, JC Camidge, DR AF Sequist, Lecia V. Soria, Jean-Charles Camidge, D. Ross TI Update to Rociletinib Data with the RECIST Confirmed Response Rate SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Sequist, Lecia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Soria, Jean-Charles] Inst Gustave Roussy, Villejuif, France. [Camidge, D. Ross] Univ Colorado, Ctr Canc, Aurora, CO USA. RP Sequist, LV (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM lvsequist@partners.org NR 4 TC 9 Z9 9 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 9 PY 2016 VL 374 IS 23 BP 2296 EP 2297 DI 10.1056/NEJMc1602688 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DO6VB UT WOS:000377920500027 PM 27195670 ER PT J AU Cheng, H Liu, P Ohlson, C Xu, E Symonds, L Isabella, A Muller, WJ Lin, NU Krop, IE Roberts, TM Winer, EP Arteaga, CL Zhao, JJ AF Cheng, H. Liu, P. Ohlson, C. Xu, E. Symonds, L. Isabella, A. Muller, W. J. Lin, N. U. Krop, I. E. Roberts, T. M. Winer, E. P. Arteaga, C. L. Zhao, J. J. TI PIK3CA(H1047R)- and Her2-initiated mammary tumors escape PI3K dependency by compensatory activation of MEK-ERK signaling SO ONCOGENE LA English DT Article ID HUMAN BREAST-CANCER; PIK3CA MUTATIONS; TRASTUZUMAB RESISTANCE; ADJUVANT CHEMOTHERAPY; METABOLIC-REGULATION; UP-REGULATION; INHIBITION; EXPRESSION; PATHWAY; IMPACT AB Human breast cancers that have HER2 amplification/overexpression frequently carry PIK3CA mutations, and are often associated with a worse prognosis. However, the role of PIK3CA mutations in the initiation and maintenance of these breast cancers remains elusive. In the present study, we generated a compound mouse model that genetically mimics HER2-positive breast cancer with coexisting PIK3CA(H1047R). Induction of PIK3CA(H1047R) expression in mouse mammary glands with constitutive expression of activated Her2/Neu resulted in accelerated mammary tumorigenesis with enhanced metastatic potential. Interestingly, inducible expression of mutant PIK3CA resulted in a robust activation of phosphatidylinositol-3-kinase (PI3K)/AKT signaling but attenuation of Her2/Her3 signaling, and this can be reversed by deinduction of PIK3CA(H1047R) expression. Strikingly, although these Her2(+) PIK3CA(H1047R) initiated primary mammary tumors are refractory to HER2-targeted therapy, all tumors responded to inactivation of the oncogenic PIK3CA(H1047R), a situation closely mimicking the use of a highly effective inhibitor specifically targeting the mutant PIK3CA/p110a. Notably, these tumors eventually resumed growth, and a fraction of them escaped PI3K dependence by compensatory ERK activation, which can be blocked by combined inhibition of Her2 and MEK. Together, these results suggest that PIK3CA-specific inhibition as a monotherapy followed by combination therapy targeting MAPK and HER2 in a timely manner may be an effective treatment approach against HER2-positive cancers with coexisting PIK3CA-activating mutations. C1 [Cheng, H.] Dalian Med Univ, Hosp 2, Inst Canc, Dalian 116023, Peoples R China. [Cheng, H.; Liu, P.; Ohlson, C.; Xu, E.; Symonds, L.; Isabella, A.; Roberts, T. M.; Zhao, J. J.] Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave Smith 936, Boston, MA 02215 USA. [Muller, W. J.] McGill Univ, Goodman Canc Res Ctr, Dept Biochem, Montreal, PQ, Canada. [Lin, N. U.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Krop, I. E.; Winer, E. P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Arteaga, C. L.] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA. RP Cheng, H (reprint author), Dalian Med Univ, Hosp 2, Inst Canc, Dalian 116023, Peoples R China.; Zhao, JJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave Smith 936, Boston, MA 02215 USA. EM hailingcheng_dmu@163.com; jean_zhao@dfci.harvard.edu FU Susan G. Komen Breast Cancer Foundation [CCR12225834]; Susan G. Komen Breast Cancer Foundation; Breast Cancer Research Foundation; ACS [CRP-07-234-06-COUN]; NIH [CA187918, CA172461-01, 1P50CA168504] FX We thank Dr Roderick Bronson and the Dana-Farber/Harvard Cancer Center Rodent Histoplathology Core for histopathological analyses. We thank L. Chodosh (University of Pennsylvania School of Medicine) for providing MMTVrtTAmice. This work was supported by the Susan G. Komen Breast Cancer Foundation CCR12225834 (HC), Susan G. Komen Breast Cancer Foundation (IEK), Breast Cancer Research Foundation (NUL, EPW and JJZ), ACS grant CRP-07-234-06-COUN (CLA), NIH grants CA187918 (TMR and JJZ), CA172461-01 (JJZ) and 1P50CA168504 (TMR, IEK, EPW, NUL and JJZ). NR 36 TC 2 Z9 2 U1 1 U2 2 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 JUN 9 PY 2016 VL 35 IS 23 BP 2961 EP 2970 DI 10.1038/onc.2015.377 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA DO0NB UT WOS:000377474500002 PM 26640141 ER PT J AU Ghiassian, SD Menche, J Chasman, DI Giulianini, F Wang, RS Ricchiuto, P Aikawa, M Iwata, H Muller, C Zeller, T Sharma, A Wild, P Lackner, K Singh, S Ridker, PM Blankenberg, S Barabasi, AL Loscalzo, J AF Ghiassian, Susan Dina Menche, Jorg Chasman, Daniel I. Giulianini, Franco Wang, Ruisheng Ricchiuto, Piero Aikawa, Masanori Iwata, Hiroshi Mueller, Christian Zeller, Tania Sharma, Amitabh Wild, Philipp Lackner, Karl Singh, Sasha Ridker, Paul M. Blankenberg, Stefan Barabasi, Albert-Laszlo Loscalzo, Joseph TI Endophenotype Network Models: Common Core of Complex Diseases SO SCIENTIFIC REPORTS LA English DT Article ID PROTEIN-INTERACTION NETWORK; MACROPHAGE POLARIZATION; DENSITY-LIPOPROTEIN; MASS-SPECTROMETRY; CAROTID-ARTERY; CASPASE 7; INFLAMMATION; ATHEROSCLEROSIS; MECHANISMS; THROMBOSIS AB Historically, human diseases have been differentiated and categorized based on the organ system in which they primarily manifest. Recently, an alternative view is emerging that emphasizes that different diseases often have common underlying mechanisms and shared intermediate pathophenotypes, or endo(pheno)types. Within this framework, a specific disease's expression is a consequence of the interplay between the relevant endophenotypes and their local, organ-based environment. Important examples of such endophenotypes are inflammation, fibrosis, and thrombosis and their essential roles in many developing diseases. In this study, we construct endophenotype network models and explore their relation to different diseases in general and to cardiovascular diseases in particular. We identify the local neighborhoods (module) within the interconnected map of molecular components, i.e., the subnetworks of the human interactome that represent the inflammasome, thrombosome, and fibrosome. We find that these neighborhoods are highly overlapping and significantly enriched with disease-associated genes. In particular they are also enriched with differentially expressed genes linked to cardiovascular disease (risk). Finally, using proteomic data, we explore how macrophage activation contributes to our understanding of inflammatory processes and responses. The results of our analysis show that inflammatory responses initiate from within the cross-talk of the three identified endophenotypic modules. C1 [Ghiassian, Susan Dina; Menche, Jorg; Sharma, Amitabh; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Networks Res, Boston, MA 02115 USA. [Ghiassian, Susan Dina; Menche, Jorg; Sharma, Amitabh; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Ghiassian, Susan Dina; Menche, Jorg; Sharma, Amitabh; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Menche, Jorg; Barabasi, Albert-Laszlo] Budapest Univ Technol & Econ, Dept Theoret Phys, Budapest, Hungary. [Chasman, Daniel I.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. [Chasman, Daniel I.; Ridker, Paul M.] Harvard Univ, Sch Med, Boston, MA USA. [Giulianini, Franco] Brigham & Womens Hosp, Informaton Syst, 75 Francis St, Boston, MA 02115 USA. [Wang, Ruisheng; Loscalzo, Joseph] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA USA. [Ricchiuto, Piero; Aikawa, Masanori; Iwata, Hiroshi; Singh, Sasha] Harvard Univ, Sch Med, Ctr Interdisciplinary Cardiovasc Sci, Brigham & Womens Hosp, Boston, MA USA. [Mueller, Christian; Zeller, Tania; Blankenberg, Stefan] Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany. [Mueller, Christian; Zeller, Tania; Wild, Philipp; Lackner, Karl; Blankenberg, Stefan] German Ctr Cardiovasc Res DZHK, Partner Site Hamburg Lubeck Kiel, Hamburg, Germany. [Sharma, Amitabh; Barabasi, Albert-Laszlo] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp,Channing Div Network Med, Boston, MA USA. [Wild, Philipp] Univ Med Ctr Mainz, Dept Med 2, Prevent Cardiol & Prevent Med, Mainz, Germany. [Wild, Philipp] Univ Med Ctr Mainz, Ctr Thrombosis & Hemostasis, Clin Epidemiol, Mainz, Germany. [Lackner, Karl] Univ Med Ctr Mainz, Inst Clin Chem & Lab Med, Mainz, Germany. [Barabasi, Albert-Laszlo] Cent European Univ, Ctr Network Sci, Budapest, Hungary. RP Loscalzo, J (reprint author), Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA USA. EM jloscalzo@partners.org RI Menche, Jorg/G-3994-2015 OI Menche, Jorg/0000-0002-1583-6404 FU NIH [HL61795, HL048743, HL108630, HL119145, 1P50HG4233]; Kowa Company, Ltd. FX This work was supported by NIH grants: HL61795, HL048743, HL108630 (MAPGen), and HL119145 (to JL), 1P50HG4233 (CEGS) (to ALB), and a research grant from Kowa Company, Ltd. (to MA). We would like to thank E. Guney, M. Saltolini, Stephanie C. Tribuna, M. Kitsak, A. Karma, Ramy Arnaout, for their help and suggestions. NR 65 TC 3 Z9 3 U1 2 U2 5 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 JUN 9 PY 2016 VL 6 AR 27414 DI 10.1038/srep27414 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DN8OS UT WOS:000377339100001 PM 27278246 ER PT J AU Bashan, A Gibson, TE Friedman, J Carey, VJ Weiss, ST Hohmann, EL Liu, YY AF Bashan, Amir Gibson, Travis E. Friedman, Jonathan Carey, Vincent J. Weiss, Scott T. Hohmann, Elizabeth L. Liu, Yang-Yu TI Universality of human microbial dynamics SO NATURE LA English DT Article ID HUMAN GUT MICROBIOME; DIVERSITY; TRANSPLANTATION; ENTEROTYPES; DISEASE; MODELS; HEALTH AB Human-associated microbial communities have a crucial role in determining our health and well-being(1,2), and this has led to the continuing development of microbiome-based therapies(3) such as faecal microbiota transplantation(4,5). These microbial communities are very complex, dynamic(6) and highly personalized ecosystems(3,7), exhibiting a high degree of inter-individual variability in both species assemblages(8) and abundance profiles(9). It is not known whether the underlying ecological dynamics of these communities, which can be parameterized by growth rates, and intra-and inter-species interactions in population dynamics models(10), are largely host-independent (that is, universal) or host-specific. If the inter-individual variability reflects host-specific dynamics due to differences in host lifestyle(11), physiology(12) or genetics(13), then generic microbiome manipulations may have unintended consequences, rendering them ineffective or even detrimental. Alternatively, microbial ecosystems of different subjects may exhibit universal dynamics, with the inter-individual variability mainly originating from differences in the sets of colonizing species(7,14). Here we develop a new computational method to characterize human microbial dynamics. By applying this method to cross-sectional data from two large-scale metagenomic studiesthe Human Microbiome Project(9,15) and the Student Microbiome Project(16)-we show that gut and mouth microbiomes display pronounced universal dynamics, whereas communities associated with certain skin sites are probably shaped by differences in the host environment. Notably, the universality of gut microbial dynamics is not observed in subjects with recurrent Clostridium difficile infection(17) but is observed in the same set of subjects after faecal microbiota transplantation. These results fundamentally improve our understanding of the processes that shape human microbial ecosystems, and pave the way to designing general microbiomebased therapies(18). C1 [Bashan, Amir; Gibson, Travis E.; Carey, Vincent J.; Weiss, Scott T.; Liu, Yang-Yu] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Bashan, Amir; Gibson, Travis E.; Carey, Vincent J.; Weiss, Scott T.; Hohmann, Elizabeth L.; Liu, Yang-Yu] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Friedman, Jonathan] MIT, Dept Phys, Phys Living Syst, Cambridge, MA 02139 USA. [Hohmann, Elizabeth L.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02115 USA. [Liu, Yang-Yu] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Liu, YY (reprint author), Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.; Liu, YY (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.; Liu, YY (reprint author), Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. EM yyl@channing.harvard.edu FU John Templeton Foundation [51977]; National Institutes of Health [R01 HL091528] FX We thank E. K. Silverman, G. Weinstock, C. Huttenhower, R. Knight, G. Ackermann, D. Del Vecchio, D. Lauffenburger, G. Abu-Ali, J. Sordillo, M. McGeachie, and J. Gore for discussions. Special thanks to A.-L. Barabasi and J. Loscalzo for careful reading of the manuscript. This work was partially supported by the John Templeton Foundation (award number 51977) and National Institutes of Health (R01 HL091528). NR 38 TC 9 Z9 9 U1 29 U2 78 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JUN 9 PY 2016 VL 534 IS 7606 BP 259 EP + DI 10.1038/nature18301 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DO0NH UT WOS:000377475100043 PM 27279224 ER PT J AU Peters, C Nigim, F Chiocca, EA Rabkin, SD AF Peters, Cole Nigim, Fares Chiocca, E. Antonio Rabkin, Samuel D. TI Oncolytic viruses on the cusp of success?: proceedings of the 9th International Conference on Oncolytic Virus Therapeutics SO MOLECULAR THERAPY-ONCOLYTICS LA English DT Editorial Material ID CANCER; METASTASES; EXPRESSION; THERAPY AB Boston, Massachusetts, was the site of the 9th International Conference on Oncolytic Virus Therapeutics held 13-16 June 2015. An overarching theme of the meeting was the continued development of combinatorial treatment regimens to bolster the therapeutic potential of oncolytic viruses (OVs). Several talks focused on combining OVs with immune checkpoint inhibitors in a wide array of tumors, signaling an experimental and thematic shift toward driving immune activation to clear a tumor versus relying on direct viral oncolysis. An important aspect of the meeting was the variety of ongoing OV clinical trials. Topics ranged from basic virology to clinical trials and from academic research to intellectual property and biotechnology. There was much excitement due to the US Food and Drug Administration's recent consideration of talimogene laherparepvec (T-VEC) for the treatment of advanced melanoma (T-VEC was approved in October, following the conference). Here, we summarize the meeting's primary themes, which reflect the current state of the field. C1 [Peters, Cole; Nigim, Fares; Chiocca, E. Antonio; Rabkin, Samuel D.] Harvard Med Sch, Dept Neurosurg, Boston, MA 02215 USA. [Peters, Cole; Nigim, Fares; Rabkin, Samuel D.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Peters, Cole; Rabkin, Samuel D.] Harvard Med Sch, Program Virol, Boston, MA 02115 USA. [Chiocca, E. Antonio] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. RP Rabkin, SD (reprint author), Harvard Med Sch, Dept Neurosurg, Boston, MA 02215 USA.; Rabkin, SD (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.; Rabkin, SD (reprint author), Harvard Med Sch, Program Virol, Boston, MA 02115 USA. EM rabkin@mgh.harvard.edu NR 14 TC 2 Z9 2 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2372-7705 J9 Mol Ther-Oncolytics JI Mol. Ther.-Oncolytics PD JUN 8 PY 2016 VL 3 AR UNSP 16016 DI 10.1038/mto.2016.16 PG 4 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA EE2US UT WOS:000389441000001 ER PT J AU Kharasch, SJ McBride, DR Saitz, R Myers, WP AF Kharasch, Sigmund J. McBride, David R. Saitz, Richard Myers, Ward P. TI Drinking to toxicity: college students referred for emergency medical evaluation SO ADDICTION SCIENCE & CLINICAL PRACTICE LA English DT Article ID BINGE-DRINKING; ALCOHOL; HEALTH; CONSEQUENCES; PREVALENCE; POLICIES; TRENDS AB Background: In 2009, a university adopted a policy of emergency department transport of students appearing intoxicated on campus. The objective was to describe the change in ED referrals after policy initiation and describe a group of students at risk for acute alcohol-related morbidity. Methods: A retrospective cohort of university students during academic years 2007-2011 (September-June) transported to local ED's was evaluated. Data were compared 2 years prior to initiation of the policy and 3 years after and included total number of ED transports and blood or breath alcohol level. Results: 971 Students were transported to local ED's. The mean number of yearly transports 2 years prior to policy initiation was 131 and 3 years after was 236 (56 % increase, p < 0.01). 92 % had a blood or breath alcohol level obtained. The mean alcohol level was 193 mg/dL. Twenty percent of students had alcohol levels greater than 250 mg/dL. Conclusions: Adoption of a university alcohol policy was followed by a significant increase in ED transports of intoxicated students. College students identified as intoxicated frequently drank to toxicity. C1 [Kharasch, Sigmund J.] Harvard Univ, Massachusetts Gen Hosp, Div Pediat Emergency Med, Sch Med, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. [McBride, David R.] Univ Maryland, Div Student Affairs, Campus Dr,Bldg 140, College Pk, MD 20742 USA. [Saitz, Richard] Boston Univ, Dept Community Hlth Sci, Sch Publ Hlth, 801 Massachusetts Ave,4th Floor, Boston, MA 02118 USA. [Myers, Ward P.] Boston Univ, Dept Emergency Med, Boston Med Ctr, Sch Med, One Boston Med Ctr Pl, Boston, MA 02118 USA. RP Kharasch, SJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Pediat Emergency Med, Sch Med, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM skharasch@partners.org NR 32 TC 1 Z9 1 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1940-0640 J9 ADDICT SCI CLIN PRAC JI Addict. Sci. Clin. Pract. PD JUN 8 PY 2016 VL 11 AR 11 DI 10.1186/s13722-016-0059-4 PG 5 WC Substance Abuse SC Substance Abuse GA DP0AX UT WOS:000378151100001 PM 27277284 ER PT J AU Pop, M Paulson, JN Chakraborty, S Astrovskaya, I Lindsay, BR Li, S Bravo, HC Harro, C Parkhill, J Walker, AW Walker, RI Sack, DA Stine, OC AF Pop, Mihai Paulson, Joseph N. Chakraborty, Subhra Astrovskaya, Irina Lindsay, Brianna R. Li, Shan Bravo, Hector Corrada Harro, Clayton Parkhill, Julian Walker, Alan W. Walker, Richard I. Sack, David A. Stine, O. Colin TI Individual-specific changes in the human gut microbiota after challenge with enterotoxigenic Escherichia coli and subsequent ciprofloxacin treatment SO BMC GENOMICS LA English DT Article DE Diarrhea; Enterotoxigenic Escherichia coli; 16S rRNA gene survey; Microbiota; Antibiotic treatment ID HUMAN INTESTINAL MICROBIOTA; LONG-TERM IMPACTS; IMMUNE-SYSTEM; DIARRHEA; MUTUALISM; COUNTRIES; RESPONSES; BACTERIA; DISEASE; CULTURE AB Background: Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea in inhabitants from low-income countries and in visitors to these countries. The impact of the human intestinal microbiota on the initiation and progression of ETEC diarrhea is not yet well understood. Results: We used 16S rRNA (ribosomal RNA) gene sequencing to study changes in the fecal microbiota of 12 volunteers during a human challenge study with ETEC (H10407) and subsequent treatment with ciprofloxacin. Five subjects developed severe diarrhea and seven experienced few or no symptoms. Diarrheal symptoms were associated with high concentrations of fecal E. coli as measured by quantitative culture, quantitative PCR, and normalized number of 16S rRNA gene sequences. Large changes in other members of the microbiota varied greatly from individual to individual, whether or not diarrhea occurred. Nonetheless the variation within an individual was small compared to variation between individuals. Ciprofloxacin treatment reorganized microbiota populations; however, the original structure was largely restored at one and three month follow-up visits. Conclusion: Symptomatic ETEC infections, but not asymptomatic infections, were associated with high fecal concentrations of E. coli. Both infection and ciprofloxacin treatment caused variable changes in other bacteria that generally reverted to baseline levels after three months. C1 [Pop, Mihai; Paulson, Joseph N.; Astrovskaya, Irina; Bravo, Hector Corrada] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA. [Pop, Mihai; Bravo, Hector Corrada] Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA. [Paulson, Joseph N.] Univ Maryland, Grad Program Appl Math & Sci Computat, College Pk, MD 20742 USA. [Paulson, Joseph N.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Paulson, Joseph N.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Chakraborty, Subhra; Harro, Clayton; Sack, David A.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Lindsay, Brianna R.; Li, Shan; Stine, O. Colin] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Lindsay, Brianna R.] Merck & Co Inc, N Wales, PA USA. [Parkhill, Julian; Walker, Alan W.] Wellcome Trust Sanger Inst, Pathogen Genom Grp, Hinxton, Cambs, England. [Walker, Alan W.] Univ Aberdeen, Rowett Inst Nutr & Hlth, Microbiol Grp, Aberdeen, Scotland. [Walker, Richard I.] PATH, Washington, DC USA. RP Stine, OC (reprint author), Univ Maryland, Sch Med, Baltimore, MD 21201 USA. EM ostin001@umaryland.edu OI Walker, Alan/0000-0001-5099-8495 FU NIH [R01-AI-100947, R21-GM-107683]; NSF [DGE750616]; Bill and Melinda Gates Foundation [42917]; Wellcome Trust [098051]; Rowett Institute of Nutrition and Health, University of Aberdeen; Scottish Government Rural and Environmental Science and Analysis Service (RESAS) FX IA, JNP, and MP were partly supported by the NIH, grants R01-AI-100947 to MP, and R21-GM-107683 to Matthias Chung, subcontract to MP. JNP was partly supported by an NSF graduate fellowship number DGE750616. IA, JNP, BRL, OCS and MP were supported in part by the Bill and Melinda Gates Foundation, award number 42917 to OCS. JP and AWW received core funding support from The Wellcome Trust (grant number 098051). AWW, and the Rowett Institute of Nutrition and Health, University of Aberdeen, receive core funding support from the Scottish Government Rural and Environmental Science and Analysis Service (RESAS). NR 47 TC 0 Z9 0 U1 1 U2 5 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 JUN 8 PY 2016 VL 17 AR 440 DI 10.1186/s12864-016-2777-0 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA DO1WC UT WOS:000377569600001 PM 27277524 ER PT J AU Grubbs, V Vittighoff, E Grimes, B Johansen, KL AF Grubbs, Vanessa Vittighoff, Eric Grimes, Barbara Johansen, Kirsten L. TI Mortality and illicit drug dependence among hemodialysis patients in the United States: a retrospective cohort analysis SO BMC NEPHROLOGY LA English DT Article DE Illicit drug use; Hemodialysis; Mortality ID STAGE RENAL-DISEASE; SUBSTANCE-ABUSE; TRANSPLANTATION; DIALYSIS; KIDNEY AB Background: Illicit drug use is common and known to cause and exacerbate a wide spectrum of kidney disease, often leading to end-stage renal disease (ESRD), but little is known about its prevalence or associated mortality among incident hemodialysis patients. Methods: This study is a retrospective cohort analysis using data obtained from the United States Renal Data System. We assembled a cohort of 511,821 incident hemodialysis patients age 20 years and older who initiated hemodialysis between January 1, 2006 and December 31, 2010. Illicit drug dependence was defined by comorbidity on the ESRD Medical Evidence Report (Form CMS-2728). We performed survival analysis to examine the association of drug dependence with overall mortality and mortality due to diagnoses that can be associated with intravenous drug use (drug-sensitive diagnoses) in the first year after initiating hemodialysis. Results: Drug dependence was recorded for 1.5 % (n = 7,461). Drug dependence was independently associated with a 1.3-fold and 2.5-fold higher hazard of overall mortality and mortality due to a potentially drug-sensitive diagnosis [adjusted hazard ratio (AHR) 1.34 (1.27-1.41) and 2.54 (2.05-3.14), p < 0.001, respectively]. This association varied significantly by age (p(interaction) < 0.001), with a 9-fold higher hazard of mortality due to a potentially drug-sensitive diagnosis among the youngest patients with drug dependence [AHR 9.21 (5.15-16.44), p < 0.001]. Conclusion: Illicit drug dependence is a burden within the ESRD program and is strongly associated with premature mortality, particularly among younger patients. Targeted intervention is needed to help reduce this burden. C1 [Grubbs, Vanessa; Johansen, Kirsten L.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Grubbs, Vanessa] San Francisco Gen Hosp, Div Nephrol, 1001 Potrero Ave,Bldg 100,Room 342, San Francisco, CA 94110 USA. [Vittighoff, Eric; Grimes, Barbara] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] San Francisco Vet Adm Med Ctr, Div Nephrol, San Francisco, CA USA. RP Grubbs, V (reprint author), Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA.; Grubbs, V (reprint author), San Francisco Gen Hosp, Div Nephrol, 1001 Potrero Ave,Bldg 100,Room 342, San Francisco, CA 94110 USA. EM vanessa.grubbs@ucsf.edu FU National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) [1K23DK093710-01A1, N01-DK-7-0005, 1K24DK085153]; Harold Amos Medical Faculty Development Program of the Robert Wood Johnson Foundation FX VG was supported by grant 1K23DK093710-01A1 from the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) and by the Harold Amos Medical Faculty Development Program of the Robert Wood Johnson Foundation. KLJ was supported by contract N01-DK-7-0005 and grant 1K24DK085153 from NIDDK. NR 17 TC 0 Z9 0 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2369 J9 BMC NEPHROL JI BMC Nephrol. PD JUN 8 PY 2016 VL 17 AR 56 DI 10.1186/s12882-016-0271-1 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA DO2DH UT WOS:000377589400001 PM 27278934 ER PT J AU Di Maio, R Barrett, PJ Hoffman, EK Barrett, CW Zharikov, A Borah, A Hu, XP Mccoy, J Chu, CT Burton, EA Hastings, TG Greenamyre, JT AF Di Maio, Roberto Barrett, Paul J. Hoffman, Eric K. Barrett, Caitlyn W. Zharikov, Alevtina Borah, Anupom Hu, Xiaoping Mccoy, Jennifer Chu, Charleen T. Burton, Edward A. Hastings, Teresa G. Greenamyre, J. Timothy TI alpha-Synuclein binds to TOM20 and inhibits mitochondrial protein import in Parkinson's disease SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID MAMMALIAN-CELLS; RECEPTOR TOM20; COMPLEX-I; NEURONS; OVEREXPRESSION; NEURODEGENERATION; STABILIZATION; TRANSLOCATION; INCREASES; MEMBRANES AB alpha-Synuclein accumulation and mitochondrial dysfunction have both been strongly implicated in the pathogenesis of Parkinson's disease (PD), and the two appear to be related. Mitochondrial dysfunction leads to accumulation and oligomerization of alpha-synuclein, and increased levels of alpha-synuclein cause mitochondrial impairment, but the basis for this bidirectional interaction remains obscure. We now report that certain posttranslationally modified species of alpha-synuclein bind with high affinity to the TOM20 (translocase of the outer membrane 20) presequence receptor of the mitochondrial protein import machinery. This binding prevented the interaction of TOM20 with its co-receptor, TOM22, and impaired mitochondrial protein import. Consequently, there were deficient mitochondrial respiration, enhanced production of reactive oxygen species, and loss of mitochondrial membrane potential. Examination of postmortem brain tissue from PD patients revealed an aberrant alpha-synuclein-TOM20 interaction in nigrostriatal dopaminergic neurons that was associated with loss of imported mitochondrial proteins, thereby confirming this pathogenic process in the human disease. Modest knockdown of endogenous alpha-synuclein was sufficient to maintain mitochondrial protein import in an in vivo model of PD. Furthermore, in in vitro systems, overexpression of TOM20 or a mitochondrial targeting signal peptide had beneficial effects and preserved mitochondrial protein import. This study characterizes a pathogenic mechanism in PD, identifies toxic species of wildtype alpha-synuclein, and reveals potential new therapeutic strategies for neuroprotection. C1 [Di Maio, Roberto; Barrett, Paul J.; Hoffman, Eric K.; Barrett, Caitlyn W.; Zharikov, Alevtina; Borah, Anupom; Hu, Xiaoping; Mccoy, Jennifer; Chu, Charleen T.; Burton, Edward A.; Hastings, Teresa G.; Greenamyre, J. Timothy] Univ Pittsburgh, Pittsburgh Inst Neurodegenerat Dis, Pittsburgh, PA 15213 USA. [Di Maio, Roberto; Barrett, Paul J.; Hoffman, Eric K.; Barrett, Caitlyn W.; Zharikov, Alevtina; Hu, Xiaoping; Mccoy, Jennifer; Burton, Edward A.; Hastings, Teresa G.; Greenamyre, J. Timothy] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Di Maio, Roberto] Ri MED Fdn, Palermo, Italy. [Zharikov, Alevtina; Burton, Edward A.; Greenamyre, J. Timothy] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. [Borah, Anupom] Assam Univ, Dept Life Sci & Bioinformat, Silchar 788011, India. [Chu, Charleen T.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. RP Greenamyre, JT (reprint author), Univ Pittsburgh, Pittsburgh Inst Neurodegenerat Dis, Pittsburgh, PA 15213 USA.; Greenamyre, JT (reprint author), Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA.; Greenamyre, JT (reprint author), VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. EM jgreena@pitt.edu OI Burton, Edward/0000-0002-8072-4636 FU DSF Charitable Foundation; Ri.MED Foundation; Consolidated Anti-Aging Foundation; NIH [NS095387, NS059806, ES022644, ES020718, ES020327, NS065789, AG026389, P50AG005133]; U.S. Department of Veterans Affairs [1I01BX000548]; Blechman Foundation; American Parkinson Disease Association; Department of Biotechnology, Government of India FX This work was supported by research grants from the DSF Charitable Foundation, the Ri.MED Foundation, the Consolidated Anti-Aging Foundation, NIH (NS095387, NS059806, ES022644, ES020718, ES020327, NS065789, AG026389, and P50AG005133), the U.S. Department of Veterans Affairs (1I01BX000548), the Blechman Foundation, the American Parkinson Disease Association, and the Department of Biotechnology, Government of India. NR 41 TC 15 Z9 15 U1 4 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JUN 8 PY 2016 VL 8 IS 342 AR 342ra78 DI 10.1126/scitranslmed.aaf3634 PG 14 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA DO0BG UT WOS:000377443800002 PM 27280685 ER PT J AU Sager, HB Dutta, P Dahlman, JE Hulsmans, M Courties, G Sun, Y Heidt, T Vinegoni, C Borodovsky, A Fitzgerald, K Wojtkiewicz, GR Iwamoto, Y Tricot, B Khan, OF Kauffman, KJ Xing, YP Shaw, TE Libby, P Langer, R Weissleder, R Swirski, FK Anderson, DG Nahrendorf, M AF Sager, Hendrik B. Dutta, Partha Dahlman, James E. Hulsmans, Maarten Courties, Gabriel Sun, Yuan Heidt, Timo Vinegoni, Claudio Borodovsky, Anna Fitzgerald, Kevin Wojtkiewicz, Gregory R. Iwamoto, Yoshiko Tricot, Benoit Khan, Omar F. Kauffman, Kevin J. Xing, Yiping Shaw, Taylor E. Libby, Peter Langer, Robert Weissleder, Ralph Swirski, Filip K. Anderson, Daniel G. Nahrendorf, Matthias TI RNAi targeting multiple cell adhesion molecules reduces immune cell recruitment and vascular inflammation after myocardial infarction SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID ATHEROSCLEROTIC LESIONS; SIRNA DELIVERY; P-SELECTIN; LEUKOCYTE RECRUITMENT; THERAPEUTIC SIRNA; DEFICIENT MICE; IN-VIVO; MONOCYTE; DISEASE; ENDOTHELIUM AB Myocardial infarction (MI) leads to a systemic surge of vascular inflammation in mice and humans, resulting in secondary ischemic complications and high mortality. We show that, in ApoE(-/-) mice with coronary ligation, increased sympathetic tone up-regulates not only hematopoietic leukocyte production but also plaque endothelial expression of adhesion molecules. To counteract the resulting arterial leukocyte recruitment, we developed nanoparticle-based RNA interference (RNAi) that effectively silences five key adhesion molecules. Simultaneously encapsulating small interfering RNA (siRNA)-targeting intercellular cell adhesion molecules 1 and 2 (Icam1 and Icam2), vascular cell adhesion molecule 1 (Vcam1), and E-and P-selectins (Sele and Selp) into polymeric endothelial-avid nanoparticles reduced post-MI neutrophil and monocyte recruitment into atherosclerotic lesions and decreased matrix-degrading plaque protease activity. Five-gene combination RNAi also curtailed leukocyte recruitment to ischemic myocardium. Therefore, targeted multigene silencing may prevent complications after acute MI. C1 [Sager, Hendrik B.; Dutta, Partha; Hulsmans, Maarten; Courties, Gabriel; Sun, Yuan; Heidt, Timo; Vinegoni, Claudio; Wojtkiewicz, Gregory R.; Iwamoto, Yoshiko; Tricot, Benoit; Weissleder, Ralph; Swirski, Filip K.; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Sager, Hendrik B.; Dutta, Partha; Hulsmans, Maarten; Courties, Gabriel; Sun, Yuan; Heidt, Timo; Vinegoni, Claudio; Wojtkiewicz, Gregory R.; Iwamoto, Yoshiko; Tricot, Benoit; Weissleder, Ralph; Swirski, Filip K.; Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Dahlman, James E.; Xing, Yiping; Shaw, Taylor E.; Langer, Robert; Anderson, Daniel G.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Dahlman, James E.; Khan, Omar F.; Kauffman, Kevin J.; Xing, Yiping; Shaw, Taylor E.; Langer, Robert; Anderson, Daniel G.] MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Dahlman, James E.; Langer, Robert; Anderson, Daniel G.] MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Borodovsky, Anna; Fitzgerald, Kevin] Alnylam Pharmaceut, Cambridge, MA 02142 USA. [Kauffman, Kevin J.; Langer, Robert; Anderson, Daniel G.] MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Libby, Peter] Brigham & Womens Hosp, Dept Med, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Nahrendorf, Matthias] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Sager, HB; Nahrendorf, M (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.; Sager, HB; Nahrendorf, M (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA.; Nahrendorf, M (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM hendrik.sager@tum.de; mnahrendorf@mgh.harvard.edu FU NIH [HL114477, HL117829, HL096576, K99-HL121076]; MGH Research Scholar Award; Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH) [UL1 TR001102]; Deutsche Forschungsgemeinschaft [SA1668/2-1, HE-6382/1-1] FX This work was funded by grants from the NIH (HL114477, HL117829, HL096576, and K99-HL121076), the MGH Research Scholar Award, and Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH Award UL1 TR001102). H.B.S. and T.H. were funded by Deutsche Forschungsgemeinschaft (SA1668/2-1 and HE-6382/1-1). NR 50 TC 9 Z9 9 U1 9 U2 15 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JUN 8 PY 2016 VL 8 IS 342 AR 342ra80 DI 10.1126/scitranslmed.aaf1435 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA DO0BG UT WOS:000377443800004 PM 27280687 ER PT J AU Diaz-Ochoa, VE Lam, D Lee, CS Klaus, S Behnsen, J Liu, JZ Chim, N Nuccio, SP Rathi, SG Mastroianni, JR Edwards, RA Jacobo, CM Cerasi, M Battistoni, A Ouellette, AJ Goulding, CW Chazin, WJ Skaar, EP Raffatellu, M AF Diaz-Ochoa, Vladimir E. Lam, Diana Lee, Carlin S. Klaus, Suzi Behnsen, Judith Liu, Janet Z. Chim, Nicholas Nuccio, Sean-Paul Rathi, Subodh G. Mastroianni, Jennifer R. Edwards, Robert A. Jacobo, Christina M. Cerasi, Mauro Battistoni, Andrea Ouellette, Andre J. Goulding, Celia W. Chazin, Walter J. Skaar, Eric P. Raffatellu, Manuela TI Salmonella Mitigates Oxidative Stress and Thrives in the Inflamed Gut by Evading Calprotectin-Mediated Manganese Sequestration SO CELL HOST & MICROBE LA English DT Article ID ENTERICA SEROVAR TYPHIMURIUM; INNATE IMMUNE-RESPONSE; IRON TRANSPORT-SYSTEM; HOST-DEFENSE PROTEIN; SUPEROXIDE-DISMUTASE; INTESTINAL MICROBIOTA; ESCHERICHIA-COLI; FULL VIRULENCE; BACTERIAL; INFLAMMATION AB Neutrophils hinder bacterial growth by a variety of antimicrobial mechanisms, including the production of reactive oxygen species and the secretion of proteins that sequester nutrients essential to microbes. A major player in this process is calprotectin, a host protein that exerts antimicrobial activity by chelating zinc and manganese. Here we show that the intestinal pathogen Salmonella enterica serovar Typhimurium uses specialized metal transporters to evade calprotectin sequestration of manganese, allowing the bacteria to outcompete commensals and thrive in the inflamed gut. The pathogen's ability to acquire manganese in turn promotes function of SodA and KatN, enzymes that use the metal as a cofactor to detoxify reactive oxygen species. This manganese-dependent SodA activity allows the bacteria to evade neutrophil killing mediated by calprotectin and reactive oxygen species. Thus, manganese acquisition enables S. Typhimurium to overcome host antimicrobial defenses and support its competitive growth in the intestine. C1 [Diaz-Ochoa, Vladimir E.; Lam, Diana; Lee, Carlin S.; Klaus, Suzi; Behnsen, Judith; Liu, Janet Z.; Nuccio, Sean-Paul; Jacobo, Christina M.; Raffatellu, Manuela] Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA. [Diaz-Ochoa, Vladimir E.; Lam, Diana; Lee, Carlin S.; Klaus, Suzi; Behnsen, Judith; Liu, Janet Z.; Nuccio, Sean-Paul; Jacobo, Christina M.; Raffatellu, Manuela] Univ Calif Irvine, Inst Immunol, Irvine, CA 92697 USA. [Chim, Nicholas; Goulding, Celia W.] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA. [Goulding, Celia W.] Univ Calif Irvine, Dept Pharmaceut Sci, Irvine, CA 92697 USA. [Rathi, Subodh G.; Chazin, Walter J.] Vanderbilt Univ, Dept Biochem & Chem, Nashville, TN 37232 USA. [Mastroianni, Jennifer R.; Ouellette, Andre J.] Univ So Calif, Dept Pathol & Lab Med, Los Angeles, CA 90089 USA. [Edwards, Robert A.] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92697 USA. [Cerasi, Mauro; Battistoni, Andrea] Univ Roma Tor Vergata, Dept Biol, I-00173 Rome, Italy. [Skaar, Eric P.] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA. [Skaar, Eric P.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA. RP Raffatellu, M (reprint author), Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA.; Raffatellu, M (reprint author), Univ Calif Irvine, Inst Immunol, Irvine, CA 92697 USA. EM manuelar@uci.edu OI Nuccio, Sean-Paul/0000-0002-9683-9278; Battistoni, Andrea/0000-0003-4085-7917; Raffatellu, Manuela/0000-0001-6487-4215 FU Public Health Service Grants (PHSGs) [AI83663, AI101784, AI105374, AI114625, DK058057]; Burroughs Wellcome Fund; National Institutes of Health (NIH) Minority Biomedical Research Support Initiative for Maximizing Student Development grant [GM055246]; NIH [T32 AI60573]; PHSG [AI101171]; Office of Medical Research, Department of Veterans Affairs [BX002482]; PHSGs [AI099687, AI095208] FX We thank Russell Gerards for help with ICP-MS. M.R.'s lab is supported by Public Health Service Grants (PHSGs) AI83663, AI101784, AI105374, AI114625, and DK058057. M.R. holds an Investigator in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund. Other M.R. lab support: V.E.D.-O. by National Institutes of Health (NIH) Minority Biomedical Research Support Initiative for Maximizing Student Development grant GM055246 and a University of California, Irvine, President's Dissertation Year Award; S.K. by an American Heart Association (AHA) predoctoral fellowship; J.Z.L. by NIH grant T32 AI60573 and an AHA predoctoral fellowship; J.B. by an AHA postdoctoral fellowship. E.P.S.'s and W.J.C.'s labs are supported by PHSG AI101171. E.P.S. holds a Merit Review Grant (BX002482) from the Office of Medical Research, Department of Veterans Affairs. C.W.G.'s lab is supported by PHSGs AI099687 and AI095208. NR 66 TC 4 Z9 4 U1 5 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 EI 1934-6069 J9 CELL HOST MICROBE JI Cell Host Microbe PD JUN 8 PY 2016 VL 19 IS 6 BP 814 EP 825 DI 10.1016/j.chom.2016.05.005 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA DO0CM UT WOS:000377447000012 PM 27281571 ER PT J AU Nairn, BL Lonergan, ZR Wang, JF Braymer, JJ Zhang, YF Calcutt, MW Lisher, JP Gilston, BA Chazin, WJ de Crecy-Lagard, V Giedroc, DP Skaar, EP AF Nairn, Brittany L. Lonergan, Zachery R. Wang, Jiefei Braymer, Joseph J. Zhang, Yaofang Calcutt, M. Wade Lisher, John P. Gilston, Benjamin A. Chazin, Walter J. de Crecy-Lagard, Valerie Giedroc, David P. Skaar, Eric P. TI The Response of Acinetobacter baumannii to Zinc Starvation SO CELL HOST & MICROBE LA English DT Article ID METAL HOMEOSTASIS; ESCHERICHIA-COLI; BACILLUS-SUBTILIS; COG0523 FAMILY; HISTIDINE; PROTEIN; INHIBITION; ACTIVATION; INSIGHTS; GTPASE AB Zinc (Zn) is an essential metal that vertebrates sequester from pathogens to protect against infection. Investigating the opportunistic pathogen Acinetobacter baumannii's response to Zn starvation, we identified a putative Zn metallochaperone, ZigA, which binds Zn and is required for bacterial growth under Zn-limiting conditions and for disseminated infection in mice. ZigA is encoded adjacent to the histidine (His) utilization (Hut) system. The His ammonialyase HutH binds Zn very tightly only in the presence of high His and makes Zn bioavailable through His catabolism. The released Zn enables A. baumannii to combat host-imposed Zn starvation. These results demonstrate that A. baumannii employs several mechanisms to ensure bioavailability of Zn during infection, with ZigA functioning predominately during Zn starvation, but HutH operating in both Zn-deplete and -replete conditions to mobilize a labile His-Zn pool. C1 [Nairn, Brittany L.; Lonergan, Zachery R.; Skaar, Eric P.] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA. [Wang, Jiefei; Braymer, Joseph J.; Lisher, John P.; Giedroc, David P.] Indiana Univ, Dept Chem, Bloomington, IN 47405 USA. [Zhang, Yaofang; Calcutt, M. Wade] Vanderbilt Univ, Sch Med, Mass Spectrometry Res Ctr, Nashville, TN 37232 USA. [Gilston, Benjamin A.; Chazin, Walter J.] Vanderbilt Univ, Sch Med, Struct Biol Ctr, Nashville, TN 37232 USA. [Zhang, Yaofang; Calcutt, M. Wade; Chazin, Walter J.] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA. [Chazin, Walter J.] Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA. [de Crecy-Lagard, Valerie] Univ Florida, Dept Microbiol & Cell Sci, Gainesville, FL 32611 USA. [Skaar, Eric P.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37232 USA. RP Skaar, EP (reprint author), Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA.; Giedroc, DP (reprint author), Indiana Univ, Dept Chem, Bloomington, IN 47405 USA.; Skaar, EP (reprint author), US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37232 USA. EM giedroc@indiana.edu; eric.skaar@vanderbilt.edu FU NIH [R01 AI1091771, R01 AI101171, R01 GM042569, R01 GM70641]; NIAID [F32 AI108192]; Childhood Infection Research Program [T32 AI095202]; Training Program in Environmental Toxicology [T32 ES007028] FX Work presented in this manuscript was supported by grants R01 AI1091771, R01 AI101171, and R01 GM042569 from the NIH. B.L.N. was supported by grant F32 AI108192 from the NIAID and the Childhood Infection Research Program T32 AI095202. Z.R.L. is supported by the Training Program in Environmental Toxicology T32 ES007028. V.d.C.-L. is supported by the grant R01 GM70641 from the NIH. The content of this article does not necessarily represent the views of the NIH or NIAID and is solely the responsibility of the authors. NR 39 TC 5 Z9 5 U1 3 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 EI 1934-6069 J9 CELL HOST MICROBE JI Cell Host Microbe PD JUN 8 PY 2016 VL 19 IS 6 BP 826 EP 836 DI 10.1016/j.chom.2016.05.007 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA DO0CM UT WOS:000377447000013 PM 27281572 ER PT J AU Khan, S Hashmi, JA Mamashli, F Bharadwaj, HM Ganesan, S Michmizos, KP Kitzbichler, MG Zetino, M Garel, KLA Hamalainen, MS Kenet, T AF Khan, Sheraz Hashmi, Javeria A. Mamashli, Fahimeh Bharadwaj, Hari M. Ganesan, Santosh Michmizos, Konstantinos P. Kitzbichler, Manfred G. Zetino, Manuel Garel, Keri-Lee A. Hamalainen, Matti S. Kenet, Tal TI Altered Onset Response Dynamics in Somatosensory Processing in Autism Spectrum Disorder SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE autism spectrum disorders (ASD); magnetoencephalography (MEG); somatosensory cortex; feedforward; feedback; tactile sensing; cortical connectivity; biomarker ID SPACE SEPARATION METHOD; HIGH-FUNCTIONING AUTISM; RESTING-STATE NETWORKS; SURFACE-BASED ANALYSIS; BRAIN CONNECTIVITY; EVOKED-RESPONSES; CORTICAL SURFACE; COORDINATE SYSTEM; EEG-DATA; CORTEX AB Abnormalities in cortical connectivity and evoked responses have been extensively documented in autism spectrum disorder (ASD). However, specific signatures of these cortical abnormalities remain elusive, with data pointing toward abnormal patterns of both increased and reduced response amplitudes and functional connectivity. We have previously proposed, using magnetoencephalography (MEG) data, that apparent inconsistencies in prior studies could be reconciled if functional connectivity in ASD was reduced in the feedback (top-down) direction, but increased in the feedforward (bottom-up) direction. Here, we continue this line of investigation by assessing abnormalities restricted to the onset, feedforward inputs driven, component of the response to vibrotactile stimuli in somatosensory cortex in ASD. Using a novel method that measures the spatio-temporal divergence of cortical activation, we found that relative to typically developing participants, the ASD group was characterized by an increase in the initial onset component of the cortical response, and a faster spread of local activity. Given the early time window, the results could be interpreted as increased thalamocortical feedforward connectivity in ASD, and offer a plausible mechanism for the previously observed increased response variability in ASD, as well as for the commonly observed behaviorally measured tactile processing abnormalities associated with the disorder. C1 [Khan, Sheraz; Hashmi, Javeria A.; Mamashli, Fahimeh; Bharadwaj, Hari M.; Ganesan, Santosh; Kitzbichler, Manfred G.; Zetino, Manuel; Garel, Keri-Lee A.; Kenet, Tal] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Khan, Sheraz; Hashmi, Javeria A.; Mamashli, Fahimeh; Bharadwaj, Hari M.; Ganesan, Santosh; Kitzbichler, Manfred G.; Zetino, Manuel; Garel, Keri-Lee A.; Hamalainen, Matti S.; Kenet, Tal] MGH MIT Harvard, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Khan, Sheraz; Hashmi, Javeria A.; Mamashli, Fahimeh; Bharadwaj, Hari M.; Kitzbichler, Manfred G.; Hamalainen, Matti S.; Kenet, Tal] Harvard Univ, Sch Med, Boston, MA USA. [Khan, Sheraz] MIT, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Michmizos, Konstantinos P.] Rutgers State Univ, Dept Comp Sci, Piscataway, NJ USA. [Hamalainen, Matti S.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Hamalainen, Matti S.] Aalto Univ, Sch Sci, Dept Neurosci & Biomed Engn, Espoo, Finland. [Hashmi, Javeria A.] Dalhousie Univ, Dept Anesthesia, Halifax, NS, Canada. [Kitzbichler, Manfred G.] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge, England. RP Kenet, T (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.; Kenet, T (reprint author), MGH MIT Harvard, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA.; Kenet, T (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM tal@nmr.mgh.harvard.edu FU Nancy Lurie Marks Family Foundation; Autism Speaks; Simons Foundation [SFARI 239395]; National Institute of Child Health and Development [R01HD073254]; National Center for Research Resources [P41EB015896]; National Institute for Biomedical Imaging and Bioengineering [5R01EB009048]; Cognitive Rhythms Collaborative: A Discovery Network [NFS 1042134] FX This work was supported by grants from the Nancy Lurie Marks Family Foundation (TK, SK, MK), Autism Speaks (TK), The Simons Foundation (SFARI 239395, TK), The National Institute of Child Health and Development (R01HD073254, TK), The National Center for Research Resources (P41EB015896, MH), National Institute for Biomedical Imaging and Bioengineering (5R01EB009048, MH), and the Cognitive Rhythms Collaborative: A Discovery Network (NFS 1042134, MH). NR 66 TC 1 Z9 1 U1 4 U2 5 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PD JUN 8 PY 2016 VL 10 AR 255 DI 10.3389/fnins.2016.00255 PG 10 WC Neurosciences SC Neurosciences & Neurology GA DN7HM UT WOS:000377245900001 PM 27375417 ER PT J AU Myung, W Han, CE Fava, M Mischoulon, D Papakostas, GI Heo, JY Kim, KW Kim, ST Kim, DJH Kim, DK Seo, SW Seong, JK Jeon, HJ AF Myung, W. Han, C. E. Fava, M. Mischoulon, D. Papakostas, G. I. Heo, J-Y Kim, K. W. Kim, S. T. Kim, D. J. H. Kim, D. K. Seo, S. W. Seong, J-K Jeon, H. J. TI Reduced frontal-subcortical white matter connectivity in association with suicidal ideation in major depressive disorder SO TRANSLATIONAL PSYCHIATRY LA English DT Article ID HUMAN CEREBRAL-CORTEX; SMALL-WORLD NETWORKS; PREFRONTAL CORTEX; BIPOLAR DISORDER; COMMUNITY SAMPLE; MOOD DISORDERS; BRAIN NETWORKS; IMPULSIVITY; BEHAVIOR; RISK AB Major depressive disorder (MDD) and suicidal behavior have been associated with structural and functional changes in the brain. However, little is known regarding alterations of brain networks in MDD patients with suicidal ideation. We investigated whether or not MDD patients with suicidal ideation have different topological organizations of white matter networks compared with MDD patients without suicidal ideation. Participants consisted of 24 patients with MDD and suicidal ideation, 25 age- and gender-matched MDD patients without suicidal ideation and 31 healthy subjects. A network-based statistics (NBS) and a graph theoretical analysis were performed to assess differences in the inter-regional connectivity. Diffusion tensor imaging (DTI) was performed to assess topological changes according to suicidal ideation in MDD patients. The Scale for Suicide Ideation (SSI) and the Korean version of the Barrett Impulsiveness Scale (BIS) were used to assess the severity of suicidal ideation and impulsivity, respectively. Reduced structural connectivity in a characterized subnetwork was found in patients with MDD and suicidal ideation by utilizing NBS analysis. The subnetwork included the regions of the frontosubcortical circuits and the regions involved in executive function in the left hemisphere (rostral middle frontal, pallidum, superior parietal, frontal pole, caudate, putamen and thalamus). The graph theoretical analysis demonstrated that network measures of the left rostral middle frontal had a significant positive correlation with severity of SSI (r = 0.59, P = 0.02) and BIS (r = 0.59, P = 0.01). The total edge strength that was significantly associated with suicidal ideation did not differ between MDD patients without suicidal ideation and healthy subjects. Our findings suggest that the reduced frontosubcortical circuit of structural connectivity, which includes regions associated with executive function and impulsivity, appears to have a role in the emergence of suicidal ideation in MDD patients. C1 [Myung, W.; Heo, J-Y; Kim, D. J. H.; Kim, D. K.; Jeon, H. J.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, Seoul, South Korea. [Han, C. E.; Seong, J-K] Korea Univ, Inst Hlth Sci, Dept Biomed Engn, Seoul, South Korea. [Han, C. E.] Korea Univ, Dept Elect & Informat Engn, Sejong, South Korea. [Fava, M.; Mischoulon, D.; Papakostas, G. I.; Jeon, H. J.] Harvard Med Sch, Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA USA. [Kim, S. T.] Sungkyunkwan Univ, Med, Samsung Med Ctr, Dept Radiol, Seoul, South Korea. [Seo, S. W.] Sungkyunkwan Univ, Samsung Med Ctr, Sch Med, Dept Neurol, Seoul, South Korea. [Jeon, H. J.] Sungkyunkwan Univ, Samsung Adv Inst Hlth Sci & Technol, Dept Clin Res Design & Evaluat, Dept Hlth Sci & Technol,Dept Med Device Managemen, Seoul, South Korea. RP Jeon, HJ (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, Seoul, South Korea.; Jeon, HJ (reprint author), Sungkyunkwan Univ, Samsung Adv Inst Hlth Sci & Technol, Dept Med Device Management & Res, Dept Hlth Sci & Technol, 145 Anam Ro, Seoul, South Korea.; Jeon, HJ (reprint author), Sungkyunkwan Univ, Samsung Adv Inst Hlth Sci & Technol, Dept Clin Res Design & Evaluat, 145 Anam Ro, Seoul, South Korea.; Seong, JK (reprint author), Korea Univ, Dept Biomed Engn, 145 Anam Ro, Seoul 136701, South Korea. EM jkseong@korea.ac.kr; jeonhj@skku.edu FU Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2011-0013064]; Original Technology Research Program for Brain Science through the National Research Foundation of Korea (NRF) - Ministry of Science ICT and Future Planning [2015M3C7A1029034]; Institute for Information and communications Technology Promotion (IITP) grant - Korea government (MSIP) [B0132-15-1003]; Samsung Medical Center Clinical Research Development Program (CRDP) Medical Center Clinical Research Development Program [SMO1131461]; National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [MSIP-2011-0013064, MSIP-2010-0028631, MSIP-2013-004157, MSIP-2014-R1A1A1008173] FX This research was mainly supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. 2011-0013064; PI, Hong Jin Jeon). This research was partially supported by the Original Technology Research Program for Brain Science through the National Research Foundation of Korea (NRF) funded by the Ministry of Science ICT and Future Planning (2015M3C7A1029034 to J-KS). This work was also supported by Institute for Information and communications Technology Promotion (IITP) grant funded by the Korea government (MSIP; No. B0132-15-1003, the development of skin adhesive patches for the monitoring and prediction of mental disorders), the Samsung Medical Center Clinical Research Development Program (CRDP) Medical Center Clinical Research Development Program Grant SMO1131461 and National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (MSIP-2011-0013064 to HJJ, MSIP-2010-0028631, MSIP-2013-004157, MSIP-2014-R1A1A1008173 to CEH). NR 82 TC 2 Z9 2 U1 5 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD JUN 7 PY 2016 VL 6 AR e835 DI 10.1038/tp.2016.110 PG 8 WC Psychiatry SC Psychiatry GA DW1QE UT WOS:000383416900007 PM 27271861 ER PT J AU Lemke, JR Geider, K Helbig, KL Heyne, HO Schutz, H Hentschel, J Courage, C Depienne, C Nava, C Heron, D Moller, RS Hjalgrim, H Lal, D Neubauer, BA Nurnberg, P Thiele, H Kurlemann, G Arnold, GL Bhambhani, V Bartholdi, D Pedurupillay, CRJ Misceo, D Frengen, E Stromme, P Dlugos, DJ Doherty, ES Bijlsma, EK Ruivenkamp, CA Hoffer, MJV Goldstein, A Rajan, DS Narayanan, V Ramsey, K Belnap, N Schrauwen, I Richholt, R Koeleman, BPC Sa, J Mendonca, C de Kovel, CGF Weckhuysen, S Hardies, K De Jonghe, P De Meirleir, L Milh, M Badens, C Lebrun, M Busa, T Francannet, C Piton, A Riesch, E Biskup, S Vogt, H Dorn, T Helbig, I Michaud, JL Laube, B Syrbe, S AF Lemke, Johannes R. Geider, Kirsten Helbig, Katherine L. Heyne, Henrike O. Schutz, Hannah Hentschel, Julia Courage, Carolina Depienne, Christel Nava, Caroline Heron, Delphine Moller, Rikke S. Hjalgrim, Helle Lal, Dennis Neubauer, Bernd A. Nurnberg, Peter Thiele, Holger Kurlemann, Gerhard Arnold, Georgianne L. Bhambhani, Vikas Bartholdi, Deborah Pedurupillay, Christeen Ramane J. Misceo, Doriana Frengen, Eirik Stromme, Petter Dlugos, Dennis J. Doherty, Emily S. Bijlsma, Emilia K. Ruivenkamp, Claudia A. Hoffer, Mariette J. V. Goldstein, Amy Rajan, Deepa S. Narayanan, Vinodh Ramsey, Keri Belnap, Newell Schrauwen, Isabelle Richholt, Ryan Koeleman, Bobby P. C. Sa, Joaquim Mendonca, Carla de Kovel, Carolien G. F. Weckhuysen, Sarah Hardies, Katia De Jonghe, Peter De Meirleir, Linda Milh, Mathieu Badens, Catherine Lebrun, Marine Busa, Tiffany Francannet, Christine Piton, Amelie Riesch, Erik Biskup, Saskia Vogt, Heinrich Dorn, Thomas Helbig, Ingo Michaud, Jacques L. Laube, Bodo Syrbe, Steffen TI Delineating the GRIN1 phenotypic spectrum: A distinct genetic NMDA receptor encephalopathy SO NEUROLOGY LA English DT Article ID DE-NOVO MUTATIONS; INTELLECTUAL DISABILITY; FOCAL EPILEPSY; DISORDERS; DIVERSITY; SUBUNITS; DISEASES; APHASIA; BINDING AB Objective:To determine the phenotypic spectrum caused by mutations in GRIN1 encoding the NMDA receptor subunit GluN1 and to investigate their underlying functional pathophysiology.Methods:We collected molecular and clinical data from several diagnostic and research cohorts. Functional consequences of GRIN1 mutations were investigated in Xenopus laevis oocytes.Results:We identified heterozygous de novo GRIN1 mutations in 14 individuals and reviewed the phenotypes of all 9 previously reported patients. These 23 individuals presented with a distinct phenotype of profound developmental delay, severe intellectual disability with absent speech, muscular hypotonia, hyperkinetic movement disorder, oculogyric crises, cortical blindness, generalized cerebral atrophy, and epilepsy. Mutations cluster within transmembrane segments and result in loss of channel function of varying severity with a dominant-negative effect. In addition, we describe 2 homozygous GRIN1 mutations (1 missense, 1 truncation), each segregating with severe neurodevelopmental phenotypes in consanguineous families.Conclusions:De novo GRIN1 mutations are associated with severe intellectual disability with cortical visual impairment as well as oculomotor and movement disorders being discriminating phenotypic features. Loss of NMDA receptor function appears to be the underlying disease mechanism. The identification of both heterozygous and homozygous mutations blurs the borders of dominant and recessive inheritance of GRIN1-associated disorders. C1 [Lemke, Johannes R.; Heyne, Henrike O.; Hentschel, Julia] Univ Leipzig Hosp & Clin, Inst Human Genet, Leipzig, Germany. [Heyne, Henrike O.] Univ Leipzig Hosp & Clin, Integrated Res & Treatment Ctr IFB Adipos Dis, Leipzig, Germany. [Geider, Kirsten; Schutz, Hannah; Laube, Bodo] Tech Univ Darmstadt, Dept Neurophysiol & Neurosensory Syst, Darmstadt, Germany. [Helbig, Katherine L.] Ambry Genet, Div Clin Genom, Aliso Viejo, CA USA. [Courage, Carolina] Inselspital Bern, Univ Childrens Hosp, Div Human Genet, Bern, Switzerland. [Courage, Carolina] Folkhalsan Inst Genet, Helsinki, Finland. [Depienne, Christel; Nava, Caroline; Weckhuysen, Sarah] Hop La Pitie Salpetriere, AP HP, INSERM, Paris, France. [Depienne, Christel; Nava, Caroline; Heron, Delphine] Univ Paris 06, Hop La Pitie Salpetriere, AP HP,U1127,CNRS,UMR 7225, Sorbonne Univ,Inst Cerveau & Moelle Epiniere ICM, Paris, France. [Depienne, Christel; Nava, Caroline; Heron, Delphine] Hop La Pitie Salpetriere, AP HP, Dept Genet, Paris, France. [Weckhuysen, Sarah] Hop La Pitie Salpetriere, AP HP, Ctr Reference Epilepsies Rares, Epilepsy Unit, Paris, France. [Moller, Rikke S.; Hjalgrim, Helle] Danish Epilepsy Ctr, Dianalund, Denmark. [Moller, Rikke S.; Hjalgrim, Helle] Univ Southern Denmark, Inst Reg Hlth Serv, Odense, Denmark. [Lal, Dennis; Nurnberg, Peter; Thiele, Holger] Univ Cologne, Cologne Ctr Genom CCG, Cologne, Germany. [Nurnberg, Peter] Univ Cologne, Ctr Mol Med Cologne CMMC, Cologne, Germany. [Lal, Dennis] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Lal, Dennis] Harvard Univ, Sch Med, Boston, MA USA. [Lal, Dennis] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Lal, Dennis] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Neubauer, Bernd A.] Univ Med Ctr Giessen & Marburg, Dept Neuropediat, Giessen, Germany. [Kurlemann, Gerhard] Univ Med Ctr Munster, Dept Neuropediat, Munster, Germany. [Arnold, Georgianne L.] Univ Pittsburgh, Sch Med, Childrens Hosp Pittsburgh, Div Med Genet,Dept Pediat, Pittsburgh, PA 15260 USA. [Goldstein, Amy; Rajan, Deepa S.] Childrens Hosp Pittsburgh, Div Child Neurol, Pittsburgh, PA 15213 USA. [Bhambhani, Vikas] Childrens Hosp & Clin Minnesota, Dept Med Genet, Minneapolis, MN USA. [Bartholdi, Deborah] Klinikum Stuttgart, Inst Clin Genet, Stuttgart, Germany. [Pedurupillay, Christeen Ramane J.; Misceo, Doriana; Frengen, Eirik] Oslo Univ Hosp, Dept Med Genet, Oslo, Norway. [Stromme, Petter] Oslo Univ Hosp, Dept Clin Neurosci Children, Women & Childrens Div, Oslo, Norway. Univ Oslo, N-0316 Oslo, Norway. [Dlugos, Dennis J.; Helbig, Ingo] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Doherty, Emily S.] Carilion Clin Childrens Hosp, Clin Genet Sect, Roanoke, VA USA. [Bijlsma, Emilia K.; Ruivenkamp, Claudia A.; Hoffer, Mariette J. V.] Leiden Univ, Med Ctr, Dept Clin Genet, NL-2300 RA Leiden, Netherlands. [Narayanan, Vinodh; Ramsey, Keri; Belnap, Newell; Schrauwen, Isabelle; Richholt, Ryan] Translat Genom Res Inst TGen, Ctr Rare Childhood Disorders, Phoenix, AZ USA. [Koeleman, Bobby P. C.; de Kovel, Carolien G. F.] UMCU, Dept Med Genet, Utrecht, Netherlands. [Sa, Joaquim; Mendonca, Carla] Ctr Hosp Algarve, Faro, Portugal. [Weckhuysen, Sarah; Hardies, Katia; De Jonghe, Peter] Univ Antwerp VIB, Dept Mol Genet, Neurogenet Grp, B-2610 Antwerp, Belgium. [Weckhuysen, Sarah; Hardies, Katia; De Jonghe, Peter] Univ Antwerp, Inst Born Bunge, Neurogenet Lab, Antwerp, Belgium. [Weckhuysen, Sarah; De Jonghe, Peter] Univ Antwerp Hosp, Div Neurol, Antwerp, Belgium. [De Meirleir, Linda] Vrije Univ Brussel, Univ Hosp, Dept Paediat Neurol, Brussels, Belgium. [Milh, Mathieu] Aix Marseille Univ, Hop Enfants La Timone, INSERM, GMGF UMR S 910, Marseille, France. [Badens, Catherine] Hop Enfants La Timone, APHM, Dept Genet Med, Marseille, France. [Busa, Tiffany] Hop Enfants La Timone, Dept Genet Med, Marseille, France. [Lebrun, Marine] CHU Hop Nord, Genet Clin, Chromosom & Mol, St Pirest En Jarez, France. [Francannet, Christine] Ctr Hosp Univ Clermont Ferrand, Serv Genet Med, Clermont Ferrand, France. [Piton, Amelie] Univ Strasbourg, Dept Med Translat & Neurogenet, IGBMC, CNRS UMR 7104,INSERM U964, Illkirch Graffenstaden, France. [Piton, Amelie] Hop Univ Strasbourg, Lab Diagnost Genet, Strasbourg, France. [Riesch, Erik; Biskup, Saskia] CeGaT GmbH, Tubingen, Germany. [Riesch, Erik; Vogt, Heinrich; Dorn, Thomas] Swiss Epilepsy Ctr, Zurich, Switzerland. [Helbig, Ingo] Univ Med Ctr Schleswig Holstein, Dept Neuropediat, Kiel Campus, Kiel, Germany. [Michaud, Jacques L.] Univ Montreal, Ctr Hosp Univ St Justine, Ctr Rech, Montreal, PQ H3C 3J7, Canada. [Michaud, Jacques L.] Univ Montreal, Dept Pediat, Montreal, PQ H3C 3J7, Canada. [Michaud, Jacques L.] Univ Montreal, Dept Neurosci, Montreal, PQ H3C 3J7, Canada. [Syrbe, Steffen] Univ Heidelberg Hosp, Dept Gen Paediat, Div Child Neurol & Inherited Metab Dis, Ctr Paediat & Adolescent Med, Heidelberg, Germany. RP Lemke, JR (reprint author), Univ Leipzig Hosp & Clin, Inst Human Genet, Leipzig, Germany. EM johannes.lemke@medizin.uni-leipzig.de RI Badens, Catherine/J-8727-2016; piton, amelie/F-1201-2013; OI Badens, Catherine/0000-0001-9024-310X; piton, amelie/0000-0003-0408-7468; Narayanan, Vinodh/0000-0002-0658-3847 FU EuroEPINOMICS-RES network within the Eurocores framework of the European Science Foundation (ESF) [32EP30_136042/1, G.A.136.11.N, FWO/ESF-ECRP]; German Federal Ministry for Education and Research (BMBF) [IonNeurONet: 01 GM1105A, FKZ: 01EO1501]; University of Kiel; German Research Foundation within the EuroEPINOMICS framework of the European Science Foundation [HE5415/3-1]; German Research Foundation (DFG) [HE5415/5-1, HE 5415/6-1]; German Ministry for Education and Research [01DH12033, MAR 10/012]; German chapter of the International League against Epilepsy (DGfE); popgen 2.0 network (P2N) through the German Ministry for Education and Research [01EY1103]; International Coordination Action (ICA) [G0E8614N]; Centre National de Genotypage (CNG, Evry, France) FX Johannes R. Lemke (32EP30_136042/1) and Peter De Jonghe (G.A.136.11.N and FWO/ESF-ECRP) received financial support within the EuroEPINOMICS-RES network (www.euroepinomics.org) within the Eurocores framework of the European Science Foundation (ESF). Saskia Biskup and Henrike Heyne received financial support from the German Federal Ministry for Education and Research (BMBF IonNeurONet: 01 GM1105A and FKZ: 01EO1501). Katia Hardies is a PhD fellow of the Institute for Science and Technology (IWT) Flanders. Ingo Helbig was supported by intramural funds of the University of Kiel, by a grant from the German Research Foundation (HE5415/3-1) within the EuroEPINOMICS framework of the European Science Foundation, and additional grants of the German Research Foundation (DFG, HE5415/5-1, HE 5415/6-1), German Ministry for Education and Research (01DH12033, MAR 10/012), and grant by the German chapter of the International League against Epilepsy (DGfE). The project also received infrastructural support through the Institute of Clinical Molecular Biology in Kiel, supported in part by DFG Cluster of Excellence "Inflammation at Interfaces" and "Future Ocean." The project was also supported by the popgen 2.0 network (P2N) through a grant from the German Ministry for Education and Research (01EY1103) and by the International Coordination Action (ICA) grant G0E8614N. Christel Depienne, Caroline Nava, and Delphine Heron received financial support for exome analyses by the Centre National de Genotypage (CNG, Evry, France). NR 23 TC 5 Z9 5 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JUN 7 PY 2016 VL 86 IS 23 BP 2171 EP 2178 DI 10.1212/WNL.0000000000002740 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DP3TB UT WOS:000378417100015 PM 27164704 ER PT J AU Laganiere, S Boes, AD Fox, MD AF Laganiere, Simon Boes, Aaron D. Fox, Michael D. TI Network localization of hemichorea-hemiballismus SO NEUROLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; MOVEMENT-DISORDERS; BASAL GANGLIA; FUNCTIONAL CONNECTIVITY; BRAIN; DISEASE; STROKE; LESION; INFARCTION; CIRCUITS AB Objective:To determine whether neuroanatomically heterogeneous strokes causing hemichorea-hemiballismus localize to a common functional network.Methods:We identified 29 cases of lesion-induced hemichorea-hemiballismus from the literature and mapped each lesion volume onto a reference brain. Using a recently validated technique termed lesion network mapping, we tested whether these lesions belonged to the same functional network. To accomplish this, the network of brain regions functionally connected to each lesion was identified using a connectome dataset from healthy participants. Network maps were overlapped to identify any region functionally connected to our set of lesions. Specificity was evaluated using a case-control design; control cohorts included a group of similar lesions randomized to different brain locations and a second group of lesions causing a separate movement disorder, asterixis. Reproducibility was evaluated using an independent cohort of 10 additional hemichorea-hemiballismus cases.Results:Lesions showed heterogeneity in anatomical location, consistent with prior reports. However, at least 90% of these lesions showed network overlap in the posterolateral putamen. This result was specific to lesions causing hemichorea-hemiballismus and reproducible in an independent cohort. The putaminal overlap site was itself connected to a broader motor network that predicted the distribution of lesions causing hemichorea-hemiballismus.Conclusions:Strokes causing hemichorea-hemiballismus, while anatomically heterogeneous, localize to a common functional network. Specifically, lesions occur in regions functionally connected to the posterolateral putamen, a region previously implicated in hyperkinetic movement disorders. Lesion network mapping may be useful in identifying the neuroanatomical substrates of heterogeneous lesion-based disorders. C1 [Laganiere, Simon; Boes, Aaron D.; Fox, Michael D.] Harvard Univ, Sch Med, Dept Neurol, Berenson Allen Ctr Noninvas Brain Stimulat,Div Co, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Boes, Aaron D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Neurol, Boston, MA USA. [Fox, Michael D.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Fox, Michael D.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Laganiere, S; Fox, MD (reprint author), Harvard Univ, Sch Med, Dept Neurol, Berenson Allen Ctr Noninvas Brain Stimulat,Div Co, Boston, MA 02115 USA.; Fox, MD (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA.; Fox, MD (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. EM slaganie@bidmc.harvard.edu; foxmdphd@gmail.com FU Sidney R. Baer Jr. research foundation; NIH/National Institute of Neurological Disorders and Stroke [5R25NS065743-05]; NIH [K23NS083741]; Dystonia Medical Research Foundation; National Parkinson Foundation; NIH; National Center for Research Resources: Harvard Clinical and Translational Science Center [UL1 RR025758] FX S.E.L. was supported by a fellowship grant from the Sidney R. Baer Jr. research foundation. A.D.B. was supported by NIH/National Institute of Neurological Disorders and Stroke grant 5R25NS065743-05. M.D.F. was supported by NIH grant K23NS083741, by the Dystonia Medical Research Foundation and by the National Parkinson Foundation. Work on this study was also supported by grants from the NIH and National Center for Research Resources: Harvard Clinical and Translational Science Center (UL1 RR025758). NR 37 TC 1 Z9 1 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JUN 7 PY 2016 VL 86 IS 23 BP 2187 EP 2195 DI 10.1212/WNL.0000000000002741 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA DP3TB UT WOS:000378417100017 PM 27170566 ER PT J AU Suarez, ER Chang, DK Sun, JS Sui, JH Freeman, GJ Signoretti, S Zhu, Q Marasco, WA AF Suarez, Eloah Rabello Chang, De-Kuan Sun, Jiusong Sui, Jianhua Freeman, Gordon J. Signoretti, Sabina Zhu, Quan Marasco, Wayne A. TI Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model SO ONCOTARGET LA English DT Article DE immune checkpoint inhibitor; T cell exhaustion; chimeric antigen receptor; carbonic anhydrase IX; interleukin-21 ID CARBONIC-ANHYDRASE IX; ADOPTIVE IMMUNOTHERAPY; IN-VIVO; CANCER-IMMUNOTHERAPY; 4-1BB COSTIMULATION; BLOCKADE; THERAPY; TUMORS; SAFETY; LEADS AB Advances in the treatment of metastatic clear cell renal cell carcinoma (ccRCC) have led to improved progression-free survival of many patients; however the therapies are toxic, rarely achieve durable long-term complete responses and are not curative. Herein we used a single bicistronic lentiviral vector to develop a new combination immunotherapy that consists of human anti-carbonic anhydrase IX (CAIX)-targeted chimeric antigen receptor (CAR) T cells engineered to secrete human anti-programmed death ligand 1 (PD-L1) antibodies at the tumor site. The local antibody delivery led to marked immune checkpoint blockade. Tumor growth diminished 5 times and tumor weight reduced 50-80% when compared with the anti-CAIX CAR T cells alone in a humanized mice model of ccRCC. The expression of PD-L1 and Ki67 in the tumors decreased and an increase in granzyme B levels was found in CAR T cells. The anti-PD-L1 IgG1 isotype, which is capable of mediating ADCC, was also able to recruit human NK cells to the tumor site in vivo. These armed second-generation CAR T cells empowered to secrete human anti-PD-L1 antibodies in the ccRCC milieu to combat T cell exhaustion is an innovation in this field that should provide renewed potential for CAR T cell immunotherapy of solid tumors where limited efficacy is currently seen. C1 [Suarez, Eloah Rabello; Chang, De-Kuan; Sun, Jiusong; Zhu, Quan; Marasco, Wayne A.] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA. [Suarez, Eloah Rabello; Chang, De-Kuan; Sun, Jiusong; Freeman, Gordon J.; Zhu, Quan; Marasco, Wayne A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Suarez, Eloah Rabello] Fac Med ABC, Dept Biochem, Av Principe Gales, Santo Andre, SP, Brazil. [Sui, Jianhua] Natl Inst Biol Sci, ZGC Life Sci Pk, Beijing, Peoples R China. [Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Signoretti, Sabina] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Marasco, WA (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA.; Marasco, WA (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA USA. EM wayne_marasco@dfci.harvard.edu RI Suarez, Eloah/C-9225-2012; OI SUI, JIANHUA/0000-0002-1272-9662 FU National Foundation for Cancer Research (NFCR, USA); Sao Paulo Research Foundation (FAPESP, Brazil) FX This research was supported by the National Foundation for Cancer Research (NFCR, USA). A research abroad scholarship was granted by Sao Paulo Research Foundation (FAPESP, Brazil) to Eloah R. Suarez. NR 47 TC 1 Z9 2 U1 4 U2 13 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JUN 7 PY 2016 VL 7 IS 23 BP 34341 EP 34355 DI 10.18632/oncotarget.9114 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DO4KS UT WOS:000377752100063 PM 27145284 ER PT J AU Chen, XL Chen, YH Wiggs, JL Pasquale, LR Sun, XH Fan, BJ AF Chen, Xueli Chen, Yuhong Wiggs, Janey L. Pasquale, Louis R. Sun, Xinghuai Fan, Bao Jian TI Association of Matrix Metalloproteinase-9 (MMP9) Variants with Primary Angle Closure and Primary Angle Closure Glaucoma SO PLOS ONE LA English DT Article ID SINGLE NUCLEOTIDE POLYMORPHISMS; MATRIX METALLOPROTEASE-9 GENE; RISK ALLELE; POPULATION; SUSCEPTIBILITY; PREVALENCE; WORLDWIDE; LINKAGE; CHINA AB Shorter axial length observed in patients with primary angle closure glaucoma (PACG) might be due to altered matrix metalloproteinase-9 (MMP9) activity resulting in ECM remodeling during eye growth and development. This study aimed to evaluate common variants in MMP9 for association with PACG. Six tag SNPs of MMP9 were genotyped in a Chinese sample of 1,030 cases, including 572 PACG and 458 primary angle closure (PAC), and 499 controls. None of 6 SNPs were significantly associated with overall PAC/PACG (P > 0.07) or with PAC/PACG subgroups (P-c > 0.18). Meta-analysis of two non-Chinese studies revealed significant association between rs17576 and PACG (ORs = 0.56, P < 0.0001); however, meta-analysis of our dataset with 4 Chinese datasets did not replicate this association (ORs = 1.23, P = 0.29). Prior significant association for rs3918249 in one Caucasian study (OR = 0.63, P = 0.006) was not replicated in meta-analysis of 3 Chinese studies including this study (ORs = 0.91, P = 0.13). Significant heterogeneity between non-Chinese and Chinese datasets precluded overall meta-analysis for rs17576 and rs3918249 (Q = 0.001 and 0.04 respectively). rs17577 was nominally associated with PACG in one Caucasian study (OR = 1.71, P = 0.02), but not in 3 Chinese studies including our study (ORs = 1.20, P = 0.07). Overall meta-analysis revealed nominal association for rs17577 and PAC/PACG (ORs = 1.26, P-c = 0.05). Meta-analysis did not show significant association between the other SNPs and PAC/PACG (P > 0.47). The largest association study to date did not find significant association between MMP9 and PAC/PACG in Chinese; meta-analysis with other Chinese datasets did not produce significant association. In most instances combination with non-Chinese datasets was not possible except for one variant showing nominally significant association. More work is needed to define the role of MMP9 variants in PACG. C1 [Chen, Xueli; Chen, Yuhong; Sun, Xinghuai] Fudan Univ, Shanghai Med Coll, Eye & Ear Nose Throat Hosp, Dept Ophthalmol & Vis Sci, Shanghai 200433, Peoples R China. [Chen, Xueli; Wiggs, Janey L.; Pasquale, Louis R.; Fan, Bao Jian] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Pasquale, Louis R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Sun, Xinghuai] Fudan Univ, State Key Lab Med Neurobiol, Inst Brain Sci, Shanghai 200433, Peoples R China. [Sun, Xinghuai] Fudan Univ, Collaborat Innovat Ctr Brain Sci, Shanghai 200433, Peoples R China. [Sun, Xinghuai] Fudan Univ, Key Lab Myopia, Minist Hlth, Shanghai 200433, Peoples R China. [Sun, Xinghuai] Fudan Univ, Shanghai Key Lab Visual Impairment & Restorat, Shanghai 200433, Peoples R China. RP Sun, XH (reprint author), Fudan Univ, Shanghai Med Coll, Eye & Ear Nose Throat Hosp, Dept Ophthalmol & Vis Sci, Shanghai 200433, Peoples R China.; Fan, BJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA.; Sun, XH (reprint author), Fudan Univ, State Key Lab Med Neurobiol, Inst Brain Sci, Shanghai 200433, Peoples R China.; Sun, XH (reprint author), Fudan Univ, Collaborat Innovat Ctr Brain Sci, Shanghai 200433, Peoples R China.; Sun, XH (reprint author), Fudan Univ, Key Lab Myopia, Minist Hlth, Shanghai 200433, Peoples R China.; Sun, XH (reprint author), Fudan Univ, Shanghai Key Lab Visual Impairment & Restorat, Shanghai 200433, Peoples R China. EM xhsun@shmu.edu.cn; baojian_fan@meei.harvard.edu FU Funds for International Cooperation and Exchange of the National Natural Science Foundation of China [81020108017]; National Natural Science Foundation of China [81570887]; Harvard Medical School Ophthalmology Distinguished Scholar Award FX This work was supported in part by the Funds for International Cooperation and Exchange of the National Natural Science Foundation of China (81020108017) (XS) and National Natural Science Foundation of China (81570887) (YC). A Harvard Medical School Ophthalmology Distinguished Scholar Award supports LRP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 1 Z9 1 U1 2 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 7 PY 2016 VL 11 IS 6 AR e0157093 DI 10.1371/journal.pone.0157093 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DO1TC UT WOS:000377561000063 PM 27272641 ER PT J AU Ly, DP Seabury, SA Jena, AB AF Ly, Dan P. Seabury, Seth A. Jena, Anupam B. TI Differences in incomes of physicians in the United States by race and sex: observational study SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID HEALTH-CARE PROFESSIONALS; GENDER-DIFFERENCES; EARNINGS; TRENDS; GAP AB OBJECTIVES To estimate differences in annual income of physicians in the United States by race and sex adjusted for characteristics of physicians and practices. DESIGN Cross sectional survey study. SETTING Nationally representative samples of US physicians. PARTICIPANTS The 2000-13 American Community Survey (ACS) included 43 213 white male, 1698 black male, 15 164 white female, and 1252 black female physicians. The 2000-08 Center for Studying Health System Change (HSC) physician surveys included 12 843 white male, 518 black male, 3880 white female, and 342 black female physicians. MAIN OUTCOME MEASURES Annual income adjusted for age, hours worked, time period, and state of residence (from ACS data). Income was adjusted for age, specialty, hours worked, time period, years in practice, practice type, and percentage of revenue from Medicare/Medicaid (from HSC physician surveys). RESULTS White male physicians had a higher median annual income than black male physicians, whereas race was not consistently associated with median income among female physicians. For example, in 2010-13 in the ACS, white male physicians had an adjusted median annual income of $253 042 (95% confidence interval $248 670 to $257 413) compared with $188 230 ($170 844 to $205 616) for black male physicians (difference $64 812; P<0.001). White female physicians had an adjusted median annual income of $163 234 ($159 912 to 166 557) compared with $152 784 ($137 927 to $167 641) for black female physicians (difference $10 450; P=0.17). $100 000 is currently equivalent to about 69 pound 000 ((sic)89 000). Patterns were unaffected by adjustment for specialty and characteristics of practice in the HSC physician surveys. CONCLUSIONS White male physicians earn substantially more than black male physicians, after adjustment for characteristics of physicians and practices, while white and black female physicians earn similar incomes to each other, but significantly less than their male counterparts. Whether these differences reflect disparities in job opportunities is important to determine. C1 [Ly, Dan P.; Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. [Seabury, Seth A.] Univ So Calif, Dept Emergency Med, 635 Downey Way,VPD Suite 210, Los Angeles, CA 90089 USA. [Seabury, Seth A.] Univ So Calif, Leonard D Schaeffer Ctr Hlth Policy & Econ, 635 Downey Way,VPD Suite 210, Los Angeles, CA 90089 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Jena, Anupam B.] Natl Bur Econ Res, Cambridge, MA 02138 USA. RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.; Jena, AB (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.; Jena, AB (reprint author), Natl Bur Econ Res, Cambridge, MA 02138 USA. EM jena@hcp.med.harvard.edu FU Office of the Director, National Institutes of Health (NIH) [1DP5OD017897-01] FX ABJ had support from the Office of the Director, National Institutes of Health (NIH Early Independence Award, Grant 1DP5OD017897-01) for the submitted work. The research conducted was independent of any involvement from the sponsors of the study. Study sponsors were not involved in study design, data interpretation, writing, or the decision to submit the article for publication. NR 24 TC 1 Z9 1 U1 1 U2 2 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 JUN 7 PY 2016 VL 353 AR i2923 DI 10.1136/bmj.i2923 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DO5YH UT WOS:000377858600002 PM 27268490 ER PT J AU Wang, YB Breedveld, S Heijmen, B Petit, SF AF Wang, Yibing Breedveld, Sebastiaan Heijmen, Ben Petit, Steven F. TI Evaluation of plan quality assurance models for prostate cancer patients based on fully automatically generated Pareto-optimal treatment plans SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE knowledge based automated planning; overlap volume histogram (OVII); plan quality assurance; prostate radiotherapy IMRT/VMAT; dose volume histogram (DVH) prediction ID INTENSITY-MODULATED RADIOTHERAPY; RADIATION-THERAPY; AT-RISK; ARC THERAPY; IMRT PLANS; OPTIMIZATION; PREDICTION AB IMRT planning with commercial Treatment Planning Systems (TPSs) is a trial-and-error process. Consequently, the quality of treatment plans may not be consistent among patients, planners and institutions. Recently, different plan quality assurance (QA) models have been proposed, that could flag and guide improvement of suboptimal treatment plans. However, the performance of these models was validated using plans that were created using the conventional trail-and-error treatment planning process. Consequently, it is challenging to assess and compare quantitatively the accuracy of different treatment planning QA models. Therefore, we created a golden standard dataset of consistently planned Pareto-optimal IMRT plans for 115 prostate patients. Next, the dataset was used to assess the performance of a treatment planning QA model that uses the overlap volume histogram (OVH). 115 prostate IMRT plans were fully automatically planned using our in-house developed TPS Erasmus-iCycle. An existing OVH model was trained on the plans of 58 of the patients. Next it was applied to predict DVHs of the rectum, bladder and anus of the remaining 57 patients. The predictions were compared with the achieved values of the golden standard plans for the rectum D-mean, V-65, and V-75, and D-mean of the anus and the bladder. For the rectum, the prediction errors (predicted-achieved) were only -0.2 +/- 0.9 Gy ( mean +/- 1 SD) for Dmean, - 1.0 +/- 1.6% for V-65, and - 0.4 +/- 1.1% for V-75. For D-mean of the anus and the bladder, the prediction error was 0.1 +/- 1.6 Gy and 4.8 +/- 4.1 Gy, respectively. Increasing the training cohort to 114 patients only led to minor improvements. A dataset of consistently planned Pareto-optimal prostate IMRT plans was generated. This dataset can be used to train new, and validate and compare existing treatment planning QA models, and has been made publicly available. The OVH model was highly accurate in predicting rectum and anus DVHs. For the bladder, larger prediction errors were observed. C1 [Wang, Yibing; Breedveld, Sebastiaan; Heijmen, Ben; Petit, Steven F.] Erasmus MC Canc Inst, Dept Radiat Oncol, Rotterdam, Netherlands. [Petit, Steven F.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Petit, Steven F.] Harvard Univ, Sch Med, Boston, MA USA. RP Wang, YB (reprint author), Erasmus MC Canc Inst, Dept Radiat Oncol, Rotterdam, Netherlands. EM y.wang.1@erasmusmc.nl FU Elekta AB, Stockholm, Sweden; Dutch Cancer Society (KWF) [EMCR 2014-6667] FX This work is in part funded by an research grant of Elekta AB, Stockholm, Sweden. SP acknowledges financial support from the Dutch Cancer Society (KWF EMCR 2014-6667). Erasmus MC Cancer Institute also has a research collaboration with Accuray Inc., Sunnyvale, USA. NR 25 TC 1 Z9 1 U1 1 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JUN 7 PY 2016 VL 61 IS 11 BP 4268 EP 4282 DI 10.1088/0031-9155/61/11/4268 PG 15 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA DN9VB UT WOS:000377427700024 PM 27203748 ER PT J AU Kashima, R Roy, S Ascano, M Martinez-Cerdeno, V Ariza-Torres, J Kim, S Louie, J Lu, Y Leyton, P Bloch, KD Kornberg, TB Hagerman, PJ Hagerman, R Lagna, G Hata, A AF Kashima, Risa Roy, Sougata Ascano, Manuel Martinez-Cerdeno, Veronica Ariza-Torres, Jeanelle Kim, Sunghwan Louie, Justin Lu, Yao Leyton, Patricio Bloch, Kenneth D. Kornberg, Thomas B. Hagerman, Paul J. Hagerman, Randi Lagna, Giorgio Hata, Akiko TI Augmented noncanonical BMP type II receptor signaling mediates the synaptic abnormality of fragile X syndrome SO SCIENCE SIGNALING LA English DT Article ID MENTAL-RETARDATION PROTEIN; FMR1 KNOCKOUT MICE; MESSENGER-RNAS; DENDRITIC SPINES; WISHFUL-THINKING; TRANSLATING POLYRIBOSOMES; NERVOUS-SYSTEM; LIM KINASES; DROSOPHILA; BINDING AB Epigenetic silencing of fragile X mental retardation 1 (FMR1) causes fragile X syndrome (FXS), a common inherited form of intellectual disability and autism. FXS correlates with abnormal synapse and dendritic spine development, but the molecular link between the absence of the FMR1 product FMRP, an RNA binding protein, and the neuropathology is unclear. We found that the messenger RNA encoding bone morphogenetic protein type II receptor (BMPR2) is a target of FMRP. Depletion of FMRP increased BMPR2 abundance, especially that of the full-length isoform that bound and activated LIM domain kinase 1 (LIMK1), a component of the noncanonical BMP signal transduction pathway that stimulates actin reorganization to promote neurite outgrowth and synapse formation. Heterozygosity for BMPR2 rescued the morphological abnormalities in neurons both in Drosophila and in mouse models of FXS, as did the postnatal pharmacological inhibition of LIMK1 activity. Compared with postmortem prefrontal cortex tissue from healthy subjects, the amount of full-length BMPR2 and of a marker of LIMK1 activity was increased in this brain region from FXS patients. These findings suggest that increased BMPR2 signal transduction is linked to FXS and that the BMPR2-LIMK1 pathway is a putative therapeutic target in patients with FXS and possibly other forms of autism. C1 [Kashima, Risa; Roy, Sougata; Kim, Sunghwan; Louie, Justin; Lu, Yao; Kornberg, Thomas B.; Lagna, Giorgio; Hata, Akiko] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Ascano, Manuel] Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA. [Martinez-Cerdeno, Veronica; Ariza-Torres, Jeanelle] Univ Calif Davis, Inst Pediat Regenerat Med, Dept Pathol, Davis, CA 95817 USA. [Martinez-Cerdeno, Veronica; Hagerman, Randi] Univ Calif Davis, MIND Med Invest Neurodev Disorders Inst, Davis, CA 95817 USA. [Leyton, Patricio; Bloch, Kenneth D.] Massachusetts Gen Hosp, Anesthesia & Crit Care, Boston, MA 02114 USA. [Hagerman, Paul J.] Univ Calif Davis, Dept Biochem & Mol Med, Davis, CA 95817 USA. RP Hata, A (reprint author), Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. EM akiko.hata@ucsf.edu FU Japan Society for the Promotion of Science; NIH [HL093154, HL108317, HD040661]; Foundation LeDucq FX R.K. is a recipient of a fellowship from Japan Society for the Promotion of Science. This work was supported by grants from the NIH (HL093154 and HL108317) and Foundation LeDucq to A.H., and from the NIH (HD040661) to P.J.H. NR 77 TC 3 Z9 3 U1 1 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1945-0877 EI 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD JUN 7 PY 2016 VL 9 IS 431 AR ra58 DI 10.1126/scisignal.aaf6060 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DO0AN UT WOS:000377441900002 PM 27273096 ER PT J AU Reuben, A Tillman, H Fontana, RJ Davern, T McGuire, B Stravitz, RT Durkalski, V Larson, AM Liou, I Fix, O Schilsky, M McCashland, T Hay, JE Murray, N Shaikh, OS Ganger, D Zaman, A Han, SB Chung, RT Smith, A Brown, R Crippin, J Harrison, ME Koch, D Munoz, S Reddy, KR Rossaro, L Satyanarayana, R Hassanein, T Hanje, AJ Olson, J Subramanian, R Karvellas, C Hameed, B Sherker, AH Robuck, P Lee, WM AF Reuben, Adrian Tillman, Holly Fontana, Robert J. Davern, Timothy McGuire, Brendan Stravitz, R. Todd Durkalski, Valerie Larson, Anne M. Liou, Iris Fix, Oren Schilsky, Michael McCashland, Timothy Hay, J. Eileen Murray, Natalie Shaikh, Obaid S. Ganger, Daniel Zaman, Atif Han, Steven B. Chung, Raymond T. Smith, Alastair Brown, Robert Crippin, Jeffrey Harrison, M. Edwyn Koch, David Munoz, Santiago Reddy, K. Rajender Rossaro, Lorenzo Satyanarayana, Raj Hassanein, Tarek Hanje, A. James Olson, Jody Subramanian, Ram Karvellas, Constantine Hameed, Bilal Sherker, Averell H. Robuck, Patricia Lee, William M. TI Outcomes in Adults With Acute Liver Failure Between 1998 and 2013 An Observational Cohort Study SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID RETROSPECTIVE COHORT; INTENSIVE-CARE; CLINICAL-TRIAL; UNITED-STATES; ENCEPHALOPATHY; COMPLICATIONS; MULTICENTER AB Background: Acute liver failure (ALF) is a rare syndrome of severe, rapid-onset hepatic dysfunction-without prior advanced liver disease-that is associated with high morbidity and mortality. Intensive care and liver transplantation provide support and rescue, respectively. Objective: To determine whether changes in causes, disease severity, treatment, or 21-day outcomes have occurred in recent years among adult patients with ALF referred to U.S. tertiary care centers. Design: Prospective observational cohort study. (ClinicalTrials.gov: NCT00518440) Setting: 31 liver disease and transplant centers in the United States. Patients: Consecutively enrolled patients-without prior advanced liver disease-with ALF (n = 2070). Measurements: Clinical features, treatment, and 21-day outcomes were compared over time annually for trends and were also stratified into two 8-year periods (1998 to 2005 and 2006 to 2013). Results: Overall clinical characteristics, disease severity, and distribution of causes remained similar throughout the study period. The 21-day survival rates increased between the two 8-year periods (overall, 67.1% vs. 75.3%; transplant-free survival [TFS], 45.1% vs. 56.2%; posttransplantation survival, 88.3% vs. 96.3% [P < 0.010 for each]). Reductions in red blood cell infusions (44.3% vs. 27.6%), plasma infusions (65.2% vs. 47.1%), mechanical ventilation (65.7% vs. 56.1%), and vasopressors (34.9% vs. 27.8%) were observed, as well as increased use of N-acetylcysteine (48.9% vs. 69.3% overall; 15.8% vs. 49.4% [P < 0.001] in patients with ALF not due to acetaminophen toxicity). When examined longitudinally, overall survival and TFS increased throughout the 16-year period. Limitations: The duration of enrollment, the number of patients enrolled, and possibly the approaches to care varied among participating sites. The results may not be generalizable beyond such specialized centers. Conclusion: Although characteristics and severity of ALF changed little over 16 years, overall survival and TFS improved significantly. The effects of specific changes in intensive care practice on survival warrant further study. C1 [Lee, William M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Baylor Univ, Med Ctr, Dallas, TX USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Washington, Seattle, WA 98195 USA. Washington Univ, St Louis, MO USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Calif Pacific Med Ctr, San Francisco, CA USA. Univ Nebraska, Omaha, NE 68182 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Columbia Univ, Med Ctr, New York, NY USA. Mayo Clin, Rochester, MN USA. Univ Pittsburgh, Pittsburgh, PA USA. Northwestern Univ, Chicago, IL 60611 USA. Oregon Hlth & Sci Univ, Portland, OR USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Michigan, Ann Arbor, MI 48109 USA. Yale Univ, New Haven, CT USA. Univ Alabama Birmingham, Birmingham, AL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Duke Univ, Durham, NC USA. Mayo Clin, Scottsdale, AZ USA. Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. Univ Penn, Philadelphia, PA 19104 USA. Virginia Commonwealth Univ, Richmond, VA USA. Univ Calif Davis, Davis, CA 95616 USA. Mayo Clin, Jacksonville, FL 32224 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Emory Univ, Atlanta, GA 30322 USA. Univ Alberta, Edmonton, AB, Canada. NIDDK, Bethesda, MD 20892 USA. RP Lee, WM (reprint author), Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. EM william.lee@utsouthwestern.edu OI Karvellas, Constantine/0000-0002-1555-1089 FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [DK-U-01-58369] FX By the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (DK-U-01-58369). NR 19 TC 6 Z9 6 U1 1 U2 6 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 JUN 7 PY 2016 VL 164 IS 11 BP 724 EP + DI 10.7326/M15-2211 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA DO1AI UT WOS:000377510100004 PM 27043883 ER PT J AU Waks, JW Sitlani, CM Soliman, EZ Kabir, M Ghafoori, E Biggs, ML Henrikson, CA Sotoodehnia, N Biering-Sorensen, T Agarwal, SK Siscovick, DS Post, WS Solomon, SD Buxton, AE Josephson, ME Tereshchenko, LG AF Waks, Jonathan W. Sitlani, Colleen M. Soliman, Elsayed Z. Kabir, Muammar Ghafoori, Elyar Biggs, Mary L. Henrikson, Charles A. Sotoodehnia, Nona Biering-Sorensen, Tor Agarwal, Sunil K. Siscovick, David S. Post, Wendy S. Solomon, Scott D. Buxton, Alfred E. Josephson, Mark E. Tereshchenko, Larisa G. TI Global Electric Heterogeneity Risk Score for Prediction of Sudden Cardiac Death in the General Population The Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health (CHS) Studies SO CIRCULATION LA English DT Article DE death, sudden, cardiac; electrocardiography; electrophysiology; risk assessment ID CORONARY-ARTERY-DISEASE; INCIDENT HEART-FAILURE; VENTRICULAR GRADIENT; ATRIAL-FIBRILLATION; OLDER-ADULTS; MYOCARDIAL-INFARCTION; STROKE; ASSOCIATION; ELECTROGRAM; EXPERIENCE AB Background-Asymptomatic individuals account for the majority of sudden cardiac deaths (SCDs). Development of effective, low-cost, and noninvasive SCD risk stratification tools is necessary. Methods and Results-Participants from the Atherosclerosis Risk in Communities study and Cardiovascular Health Study (n= 20 177; age, 59.3+/-10.1 years; age range, 44-100 years; 56% female; 77% white) were followed up for 14.0 years (median). Five ECG markers of global electric heterogeneity (GEH; sum absolute QRST integral, spatial QRST angle, spatial ventricular gradient [SVG] magnitude, SVG elevation, and SVG azimuth) were measured on standard 12-lead ECGs. Cox proportional hazards and competing risks models evaluated associations between GEH electrocardiographic parameters and SCD. An SCD competing risks score was derived from demographics, comorbidities, and GEH parameters. SCD incidence was 1.86 per 1000 person-years. After multivariable adjustment, baseline GEH parameters and large increases in GEH parameters over time were independently associated with SCD. Final SCD risk scores included age, sex, race, diabetes mellitus, hypertension, coronary heart disease, stroke, and GEH parameters as continuous variables. When GEH parameters were added to clinical/demographic factors, the C statistic increased from 0.777 to 0.790 (P= 0.008), the risk score classified 10-year SCD risk as high (> 5%) in 7.2% of participants, 10% of SCD victims were appropriately reclassified into a high-risk category, and only 1.4% of SCD victims were inappropriately reclassified from high to intermediate risk. The net reclassification index was 18.3%. Conclusions-Abnormal electrophysiological substrate quantified by GEH parameters is independently associated with SCD in the general population. The addition of GEH parameters to clinical characteristics improves SCD risk prediction. C1 [Waks, Jonathan W.; Buxton, Alfred E.; Josephson, Mark E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiovasc Med, Boston, MA 02215 USA. [Sitlani, Colleen M.; Biggs, Mary L.; Sotoodehnia, Nona; Siscovick, David S.] Univ Washington, Div Cardiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Sitlani, Colleen M.; Biggs, Mary L.; Sotoodehnia, Nona; Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Biggs, Mary L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Soliman, Elsayed Z.] Wake Forest Sch Med, Epidemiol Cardiol Res Ctr, Div Publ Hlth Sci, Winston Salem, NC USA. [Soliman, Elsayed Z.] Wake Forest Sch Med, Dept Med, Cardiol Sect, Winston Salem, NC USA. [Kabir, Muammar; Ghafoori, Elyar; Henrikson, Charles A.; Tereshchenko, Larisa G.] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, 3181 SW Sam Jackson Pk Rd,UHN62, Portland, OR 97239 USA. [Biering-Sorensen, Tor; Solomon, Scott D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Agarwal, Sunil K.] Johns Hopkins Sch Publ Hlth, Dept Epidemiol, Internal Med, Baltimore, MD USA. [Agarwal, Sunil K.] Johns Hopkins Sch Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Siscovick, David S.] New York Acad Med, New York, NY USA. [Post, Wendy S.; Tereshchenko, Larisa G.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. RP Tereshchenko, LG (reprint author), Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, 3181 SW Sam Jackson Pk Rd,UHN62, Portland, OR 97239 USA. EM tereshch@ohsu.edu OI Tereshchenko, Larisa/0000-0002-6976-1313; Biering-Sorensen, Tor/0000-0003-4209-2778 FU National Heart, Lung, and Blood Institute [HHSN-268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN2682011-00010C, HHSN268201100011C]; National Institute of Neurological Disorders and Stroke; National Institute on Aging [R01AG023629]; The National Heart, Lung, and Blood Institute [HHSN268201100012C, HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, U01HL080295]; [1R01HL118277]; [R01HL116747]; [R01HL111089] FX The ARIC Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN-268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN2682011-00010C, HHSN268201100011C, HHSN268201100012C). CHS is supported by National Heart, Lung, and Blood Institute contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and grant U01HL080295, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by R01AG023629 from the National Institute on Aging. A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. This work was supported by 1R01HL118277 (Dr Tereshchenko), R01HL116747 (Dr Sotoodehnia), and R01HL111089 (Dr Sotoodehnia). NR 51 TC 2 Z9 2 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JUN 7 PY 2016 VL 133 IS 23 BP 2222 EP + DI 10.1161/CIRCULATIONAHA.116.021306 PG 50 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DN9ZT UT WOS:000377439900005 PM 27081116 ER PT J AU Wasfy, MM Baggish, AL AF Wasfy, Meagan M. Baggish, Aaron L. TI Exercise Dose in Clinical Practice SO CIRCULATION LA English DT Review DE exercise; hypertension; lipids; mortality ID CORONARY-HEART-DISEASE; RANDOMIZED-CONTROLLED-TRIALS; TIME PHYSICAL-ACTIVITY; ALL-CAUSE MORTALITY; DENSITY-LIPOPROTEIN-CHOLESTEROL; LIFE-STYLE INTERVENTION; HARVARD ALUMNI HEALTH; CARDIAC TROPONIN-T; BLOOD-PRESSURE; LEISURE-TIME AB There is wide variability in the physical activity patterns of the patients in contemporary clinical cardiovascular practice. This review is designed to address the impact of exercise dose on key cardiovascular risk factors and on mortality. We begin by examining the body of literature that supports a dose-response relationship between exercise and cardiovascular disease risk factors, including plasma lipids, hypertension, diabetes mellitus, and obesity. We next explore the relationship between exercise dose and mortality by reviewing the relevant epidemiological literature underlying current physical activity guideline recommendations. We then expand this discussion to critically examine recent data pertaining to the impact of exercise dose at the lowest and highest ends of the spectrum. Finally, we provide a framework for how the key concepts of exercise dose can be integrated into clinical practice. C1 [Wasfy, Meagan M.; Baggish, Aaron L.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Yawkey Ste 5B,55 Fruit St, Boston, MA 02114 USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, Yawkey Ste 5B,55 Fruit St, Boston, MA 02114 USA. EM abaggish@partners.org FU American College of Cardiology (American College of Cardiology/Merck Fellowship); National Institutes of Health [RO1 DA029141, RO1 HL117037, RO1 HL125869] FX Dr Wasfy is supported by research grant funding from the American College of Cardiology (American College of Cardiology/Merck Fellowship). Dr Baggish is supported by research grants from the National Institutes of Health (RO1 DA029141, RO1 HL117037, RO1 HL125869) NR 141 TC 2 Z9 2 U1 10 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JUN 7 PY 2016 VL 133 IS 23 BP 2297 EP 2313 DI 10.1161/CIRCULATIONAHA.116.018093 PG 17 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DN9ZT UT WOS:000377439900012 PM 27267537 ER PT J AU Santhanakrishnan, R Wang, N Larson, MG Magnani, JW McManus, DD Lubitz, SA Ellinor, PT Cheng, S Vasan, RS Lee, DS Wang, TJ Levy, D Benjamin, EJ Ho, JE AF Santhanakrishnan, Rajalakshmi Wang, Na Larson, Martin G. Magnani, Jared W. McManus, David D. Lubitz, Steven A. Ellinor, Patrick T. Cheng, Susan Vasan, Ramachandran S. Lee, Douglas S. Wang, Thomas J. Levy, Daniel Benjamin, Emelia J. Ho, Jennifer E. TI Response to Letter Regarding Article, "Atrial Fibrillation Begets Heart Failure and Vice Versa: Temporal Associations and Differences in Preserved Versus Reduced Ejection Fraction" SO CIRCULATION LA English DT Letter ID COMMUNITY C1 [Santhanakrishnan, Rajalakshmi; Magnani, Jared W.] Boston Univ, Sch Med, Dept Med, Cardiovasc Med Sect, Boston, MA 02118 USA. [Wang, Na] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiol, Boston, MA 02125 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. [Cheng, Susan; Levy, Daniel] NHLBI, Framingham, MA USA. [Cheng, Susan; Levy, Daniel] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA. [Lee, Douglas S.] Univ Toronto, Inst Clin Evaluat Sci, Toronto, ON M5S 1A1, Canada. [Lee, Douglas S.] Univ Toronto, Toronto Gen Hosp, Toronto, ON M5S 1A1, Canada. [Wang, Thomas J.] Vanderbilt Univ, Dept Med, Div Cardiovasc Med, 221 Kirkland Hall, Nashville, TN 37235 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Ho, Jennifer E.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Santhanakrishnan, R (reprint author), Boston Univ, Sch Med, Dept Med, Cardiovasc Med Sect, Boston, MA 02118 USA. OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [K23 HL116780] NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JUN 7 PY 2016 VL 133 IS 23 BP E692 EP E693 DI 10.1161/CIRCULATIONAHA.116.022835 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DN9ZT UT WOS:000377439900003 PM 27267541 ER PT J AU Song, ZR Colla, CH AF Song, Zirui Colla, Carrie H. TI Specialty-Based Global Payment A New Phase in Payment Reform SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID ONCOLOGY CARE; MEDICARE; SYSTEMS; CANCER; MODEL C1 [Song, Zirui] Massachusetts Gen Hosp, Dept Med, 55 Fruit St,Gray Bigelow 730, Boston, MA 02114 USA. [Song, Zirui] Harvard Univ, Sch Med, Boston, MA USA. [Colla, Carrie H.] Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH USA. [Colla, Carrie H.] Geisel Sch Med Dartmouth, Hanover, NH USA. RP Song, ZR (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St,Gray Bigelow 730, Boston, MA 02114 USA. EM zirui_song@post.harvard.edu FU NCATS NIH HHS [KL2 TR001088, KL2TR001088, UL1 TR001086]; NIA NIH HHS [F30 AG039175] NR 8 TC 0 Z9 0 U1 2 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 JUN 7 PY 2016 VL 315 IS 21 BP 2271 EP 2272 DI 10.1001/jama.2016.4318 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DN6KO UT WOS:000377183100011 PM 27111885 ER PT J AU Lim, SY Lu, N Oza, A Fisher, M Rai, SK Menendez, ME Choi, HK AF Lim, Sian Yik Lu, Na Oza, Amar Fisher, Mark Rai, Sharan K. Menendez, Mariano E. Choi, Hyon K. TI Trends in Gout and Rheumatoid Arthritis Hospitalizations in the United States, 1993-2011 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID HEALTH C1 [Lim, Sian Yik; Lu, Na; Oza, Amar; Fisher, Mark; Choi, Hyon K.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, 55 Fruit St,Bulfinch 165, Boston, MA 02114 USA. [Rai, Sharan K.] Arthrit Res Canada, Vancouver, BC, Canada. [Menendez, Mariano E.] Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St,Bulfinch 165, Boston, MA 02114 USA. RP Choi, HK (reprint author), Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, 55 Fruit St,Bulfinch 165, Boston, MA 02114 USA. EM hchoi@partners.org FU NIAMS NIH HHS [R01 AR065944, R01AR065944] NR 6 TC 4 Z9 4 U1 1 U2 1 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 JUN 7 PY 2016 VL 315 IS 21 BP 2345 EP 2347 DI 10.1001/jama.2016.3517 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA DN6KO UT WOS:000377183100025 PM 27272587 ER PT J AU Quill, TE Back, AL Block, SD AF Quill, Timothy E. Back, Anthony L. Block, Susan D. TI Responding to a Request for Physician-Assisted Death Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Quill, Timothy E.] Univ Rochester, Med Ctr, 601 Elmwood Ave,POB 687,Room G-7824, Rochester, NY 14642 USA. [Back, Anthony L.] Univ Washington, Seattle, WA 98195 USA. [Block, Susan D.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Quill, TE (reprint author), Univ Rochester, Med Ctr, Palliat Care Program, 601 Elmwood Ave,POB 687,Room G-7824, Rochester, NY 14642 USA. EM timothy_quill@urmc.rochester.edu NR 5 TC 0 Z9 0 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 7 PY 2016 VL 315 IS 21 BP 2352 EP 2352 DI 10.1001/jama.2016.4045 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DN6KO UT WOS:000377183100035 PM 27272597 ER PT J AU Khera, AV Won, HH Peloso, GM Lawson, KS Bartz, TM Deng, X van Leeuwen, EM Natarajan, P Emdin, CA Bick, AG Morrison, AC Brody, JA Gupta, N Nomura, A Kessler, T Duga, S Bis, JC van Duijn, CM Cupples, LA Psaty, B Rader, DJ Danesh, J Schunkert, H McPherson, R Farrall, M Watkins, H Lander, E Wilson, JG Correa, A Boerwinkle, E Merlini, PA Ardissino, D Saleheen, D Gabriel, S Kathiresan, S AF Khera, Amit V. Won, Hong-Hee Peloso, Gina M. Lawson, Kim S. Bartz, Traci M. Deng, Xuan van Leeuwen, Elisabeth M. Natarajan, Pradeep Emdin, Connor A. Bick, Alexander G. Morrison, Alanna C. Brody, Jennifer A. Gupta, Namrata Nomura, Akihiro Kessler, Thorsten Duga, Stefano Bis, Joshua C. van Duijn, Cornelia M. Cupples, L. Adrienne Psaty, Bruce Rader, Daniel J. Danesh, John Schunkert, Heribert McPherson, Ruth Farrall, Martin Watkins, Hugh Lander, Eric Wilson, James G. Correa, Adolfo Boerwinkle, Eric Merlini, Piera Angelica Ardissino, Diego Saleheen, Danish Gabriel, Stacey Kathiresan, Sekar TI Diagnostic Yield and Clinical Utility of Sequencing Familial Hypercholesterolemia Genes in Patients With Severe Hypercholesterolemia SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE coronary artery disease; gene sequencing; genetics; low-density lipoprotein cholesterol ID MUTATION DETECTION RATE; CORONARY-HEART-DISEASE; AUTOSOMAL-DOMINANT HYPERCHOLESTEROLEMIA; MYOCARDIAL-INFARCTION; RANDOMIZED-TRIALS; ASSOCIATION; POPULATION; RISK; PARTICIPANTS; METAANALYSIS AB BACKGROUND Approximately 7% of American adults have severe hypercholesterolemia (untreated low-density lipoprotein [LDL] cholesterol >= 190 mg/dl), which may be due to familial hypercholesterolemia (FH). Lifelong LDL cholesterol elevations in FH mutation carriers may confer coronary artery disease (CAD) risk beyond that captured by a single LDL cholesterol measurement. OBJECTIVES This study assessed the prevalence of an FH mutation among those with severe hypercholesterolemia and determined whether CAD risk varies according to mutation status beyond the observed LDL cholesterol level. METHODS Three genes causative for FH (LDLR, APOB, and PCSK9) were sequenced in 26,025 participants from 7 case-control studies (5,540 CAD case subjects, 8,577 CAD-free control subjects) and 5 prospective cohort studies (11,908 participants). FH mutations included loss-of-function variants in LDLR, missense mutations in LDLR predicted to be damaging, and variants linked to FH in ClinVar, a clinical genetics database. RESULTS Among 20,485 CAD-free control and prospective cohort participants, 1,386 (6.7%) had LDL cholesterol >= 190 mg/dl; of these, only 24 (1.7%) carried an FH mutation. Within any stratum of observed LDL cholesterol, risk of CAD was higher among FH mutation carriers than noncarriers. Compared with a reference group with LDL cholesterol <130 mg/dl and no mutation, participants with LDL cholesterol >= 190 mg/dl and no FH mutation had a 6-fold higher risk for CAD (odds ratio: 6.0; 95% confidence interval: 5.2 to 6.9), whereas those with both LDL cholesterol >= 190 mg/dl and an FH mutation demonstrated a 22-fold increased risk (odds ratio: 22.3; 95% confidence interval: 10.7 to 53.2). In an analysis of participants with serial lipid measurements over many years, FH mutation carriers had higher cumulative exposure to LDL cholesterol than noncarriers. CONCLUSIONS Among participants with LDL cholesterol >= 190 mg/dl, gene sequencing identified an FH mutation in <2%. However, for any observed LDL cholesterol, FH mutation carriers had substantially increased risk for CAD. (C) 2016 by the American College of Cardiology Foundation. C1 [Khera, Amit V.; Natarajan, Pradeep; Kathiresan, Sekar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Cardiovasc Res Ctr, Boston, MA USA. [Khera, Amit V.; Natarajan, Pradeep; Kathiresan, Sekar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Khera, Amit V.; Peloso, Gina M.; Natarajan, Pradeep; Emdin, Connor A.; Bick, Alexander G.; Gupta, Namrata; Nomura, Akihiro; Lander, Eric; Gabriel, Stacey; Kathiresan, Sekar] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Won, Hong-Hee] Sungkyunkwan Univ, Samsung Med Ctr, Samsung Adv Inst Hlth Sci & Technol, Seoul, South Korea. [Peloso, Gina M.; Deng, Xuan; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Lawson, Kim S.; Morrison, Alanna C.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA. [Lawson, Kim S.; Morrison, Alanna C.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA. [Bartz, Traci M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [van Leeuwen, Elisabeth M.; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Brody, Jennifer A.; Bis, Joshua C.; Psaty, Bruce] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Nomura, Akihiro] Kanazawa Univ, Grad Sch Med Sci, Div Cardiovasc Med, Kanazawa, Ishikawa, Japan. [Kessler, Thorsten; Schunkert, Heribert] Tech Univ Munich, Deutsch Herzzentrum Munchen, Deutsch Zentrum Herz Kreislauf Forsch, D-80290 Munich, Germany. [Kessler, Thorsten; Schunkert, Heribert] Munich Heart Alliance, Munich, Germany. [Duga, Stefano] Humanitas Univ, Dept Biomed Sci, Milan, Italy. [Duga, Stefano] Humanitas Clin & Res Ctr, Milan, Italy. [Psaty, Bruce] Univ Washington, Dept Med, Seattle, WA USA. [Psaty, Bruce] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Rader, Daniel J.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. [Danesh, John] Univ Cambridge, Publ Hlth & Primary Care, Cambridge, England. [Danesh, John] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England. [Danesh, John] Univ Cambridge, Natl Inst Hlth Res Blood & Transplant Res Unit Do, Dept Publ Hlth & Primary Care, Cambridge, England. [McPherson, Ruth] Univ Ottawa, Inst Heart, Ottawa, ON, Canada. [Farrall, Martin; Watkins, Hugh] Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England. [Farrall, Martin; Watkins, Hugh] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS USA. [Correa, Adolfo] Univ Mississippi, Med Ctr, Dept Med, Jackson Heart Study, Jackson, MS USA. [Merlini, Piera Angelica] Osped Niguarda Ca Granda, Milan, Italy. [Ardissino, Diego] Univ Parma, Azienda Osped Univ Parma, Div Cardiol, I-43100 Parma, Italy. [Ardissino, Diego] ASTC Assoc Trombosi Cardiol, Pavia, Italy. [Saleheen, Danish] Univ Penn, Perelman Sch Med, Biostat & Epidemiol, Philadelphia, PA 19104 USA. RP Kathiresan, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Cardiovasc Res Ctr, Boston, MA USA.; Kathiresan, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. EM skathiresan1@mgh.harvard.edu OI Watkins, Hugh/0000-0002-5287-9016 FU British Heart Foundation [RG/13/13/30194]; U.K. Medical Research Council [MR/L003120/1]; Wellcome Trust; EU Framework 6-Bloodomics Integrated Project; Pfizer; Novartis; Merck; U.K. National Institute for Health Research Cambridge Biomedical Research Centre; European Research Council [268834]; European Commission Framework Programme 7 [HEALTH-F2-2012-279233]; National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C]; National Institute on Minority Health and Health Disparities; German Federal Ministry of Education and Research (BMBF); European Union [261123]; Fondation Leducq (CADgenomics: Understanding Coronary Artery Disease Genes) [12CVD02]; Deutsche Forschungsgemeinschaft cluster of excellence "Inflammation at Interfaces"; National Institutes of Health through the American Recovery and Reinvestment Act [5RC2HL102419]; NHLBI [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, HHSN268201200036C, HHSN268200800007C]; Boston University [N01-HC-25195]; Affymetrix, Inc. [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; National Institute on Aging [R01AG023629]; Programma di ricerca Regione-Universita Area 1-Strategic Programmes-Regione Emilia-Romagna; American College of Cardiology/Merck Fellowship award; Amarin Corporation; National Heart, Lung, and Blood Institute award [K01HL125751]; Deutsches Zentrum fur Herz-Kreislauf-Forschung rotation grant; Zoll LifeCor; Johnson Johnson; Aegerion Pharmaceuticals; Alnylam Pharmaceuticals; Eli Lilly and Company; Sanofi; AstraZeneca; Boehringer Ingelheim; Bayer; Daiichi-Sankyo; GlaxoSmithKline; Boston Scientific; Bristol-Myers Squibb; Menarini Group; National Institutes of Health; Massachusetts General Hospital; Donovan Family Foundation; Bayer Healthcare; Regeneron Pharmaceuticals; Leerink Partners; Noble Insights; Quest Diagnostics; Genomics PLC; [SFB 1123]; [RFPS-2007-3-644382]; [RC2 HL103010]; [RC2 HL102923]; [RC2 HL102924]; [5U54HG003067]; [R01 HL127564]; [N01HC55222]; [N01HC85079]; [N01HC85080]; [N01HC85081]; [N01HC85082]; [N01HC85083]; [N01HC85086]; [U01HL080295]; [R01HL087652]; [R01HL105756]; [R01HL103612]; [R01HL120393] FX Field work, genotyping, and standard clinical chemistry assays in PROMIS were principally supported by grants awarded to the University of Cambridge from the British Heart Foundation, U.K. Medical Research Council, Wellcome Trust, EU Framework 6-funded Bloodomics Integrated Project, Pfizer, Novartis, and Merck. Additional support for PROMIS was provided by the U.K. Medical Research Council (MR/L003120/1), British Heart Foundation (RG/13/13/30194), U.K. National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council (268834), and European Commission Framework Programme 7 (HEALTH-F2-2012-279233). The Jackson Heart Study is supported by contracts HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, and HHSN268201300050C from the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute on Minority Health and Health Disparities. The Munich Study is supported by the German Federal Ministry of Education and Research (BMBF) in the context of the e:Med program (e:AtheroSysMed) and the FP7 European Union project CVgenes@target (261123). Additional grants were received from the Fondation Leducq (CADgenomics: Understanding Coronary Artery Disease Genes, 12CVD02). This study was also supported through the Deutsche Forschungsgemeinschaft cluster of excellence "Inflammation at Interfaces" and SFB 1123. Funding support for "Building on GWAS for NHLBI-diseases: the U.S. CHARGE Consortium" was provided by the National Institutes of Health through the American Recovery and Reinvestment Act of 2009 (5RC2HL102419). Data for "Building on GWAS for NHLBI-diseases: the U.S. CHARGE Consortium" were provided by Eric Boerwinkle on behalf of the Atherosclerosis Risk in Communities (ARIC) Study, L. Adrienne Cupples, principal investigator for the Framingham Heart Study (FHS), and Bruce Psaty, principal investigator for the Cardiovascular Health Study (CHS). Sequencing was performed at the Baylor Genome Center (U54 HG003273). The ARIC Study is conducted as a collaborative study supported by NHLBI contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). The FHS is conducted and supported by the NHLBI in collaboration with Boston University (contract No. N01-HC-25195), and its contract with Affymetrix, Inc., for genome-wide genotyping services (contract N02-HL-6-4278), for quality control by FHS investigators using genotypes in the SNP Health Association Resource (SHARe) project. A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. This CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and NHLBI grants U01HL080295, R01HL087652, R01HL105756, R01HL103612, and R01HL120393, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided through R01AG023629 from the National Institute on Aging. A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The Italian Atherosclerosis, Thrombosis, and Vascular Biology (ATVB) Study was supported by a grant from RFPS-2007-3-644382 and Programma di ricerca Regione-Universita 2010-2012 Area 1-Strategic Programmes-Regione Emilia-Romagna.; Funding for the exome-sequencing project (ESP) was provided by RC2 HL103010 (HeartGO), RC2 HL102923 (LungGO), and RC2 HL102924 (WHISP). Exome sequencing was performed through RC2 HL102925 (BroadGO) and RC2 HL102926 (SeattleGO). Exome sequencing in ATVB, PROCARDIS, Ottawa, PROMIS, Munich Study, and the Jackson Heart Study was supported by 5U54HG003067 (to Drs. Lander and Gabriel). The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the NHLBI; the National Institutes of Health; or the U.S. Department of Health and Human Services. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Khera is supported by an American College of Cardiology/Merck Fellowship award and has received consulting fees from Merck and Amarin Corporation. Dr. Peloso is supported by National Heart, Lung, and Blood Institute award K01HL125751. Dr. Kessler is supported by a Deutsches Zentrum fur Herz-Kreislauf-Forschung rotation grant. Dr. Psaty has served on a data safety and monitoring board for a clinical trial funded by Zoll LifeCor; and on a steering committee for the Yale Open Data Access project, funded by Johnson & Johnson. Dr. Rader has received consulting fees from Aegerion Pharmaceuticals, Alnylam Pharmaceuticals, Eli Lilly and Company, Pfizer, Sanofi, and Novartis; is an inventor on a patent related to lomitapide that is owned by the University of Pennsylvania and licensed to Aegerion Pharmaceuticals; and is a cofounder of Vascular Strategies and Staten Biotechnology. Dr. Ardissino has received speaker fees from AstraZeneca, Boehringer Ingelheim, Johnson & Johnson, Bayer, Daiichi-Sankyo, GlaxoSmithKline, Eli Lilly and Company, Boston Scientific, Bristol-Myers Squibb, Menarini Group, Novartis, and Sanofi; and research grants from GlaxoSmithKline, Eli Lilly and Company, Pfizer, and Novartis. Dr. Saleheen has received grants from Pfizer and the National Institutes of Health. Dr. Kathiresan is supported by a research scholar award from the Massachusetts General Hospital, the Donovan Family Foundation, and R01 HL127564; has received grants from Bayer Healthcare, Aegerion Pharmaceuticals, and Regeneron Pharmaceuticals; consulting fees from Merck, Novartis, Sanofi, AstraZeneca, Alnylam Pharmaceuticals, Leerink Partners, Noble Insights, Quest Diagnostics, Genomics PLC, and Eli Lilly and Company; and holds equity in San Therapeutics and Catabasis Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Khera, Won, and Peloso contributed equally to this work. NR 44 TC 38 Z9 38 U1 6 U2 9 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 JUN 7 PY 2016 VL 67 IS 22 BP 2578 EP 2589 DI 10.1016/j.jacc.2016.03.520 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DN7QF UT WOS:000377271300003 PM 27050191 ER PT J AU Pagidipati, NJ Hemal, K Coles, A Mark, DB Dolor, RJ Pellikka, PA Hoffmann, U Litwin, SE Udelson, J Daubert, MA Shah, SH Martinez, B Lee, KL Douglas, PS AF Pagidipati, Neha J. Hemal, Kshipra Coles, Adrian Mark, Daniel B. Dolor, Rowena J. Pellikka, Patricia A. Hoffmann, Udo Litwin, Sheldon E. Udelson, James Daubert, Melissa A. Shah, Svati H. Martinez, Beth Lee, Kerry L. Douglas, Pamela S. TI Sex Differences in Functional and CT Angiography Testing in Patients With Suspected Coronary Artery Disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE coronary artery disease; imaging; noninvasive testing; prognosis; risk stratification ID COMPUTED-TOMOGRAPHY ANGIOGRAPHY; SYNDROME EVALUATION WISE; ISCHEMIC-HEART-DISEASE; CARDIAC SYNDROME-X; CLINICAL CHARACTERISTICS; GENDER-DIFFERENCES; PROGNOSTIC VALUE; CHEST-PAIN; FOLLOW-UP; DIAGNOSIS AB BACKGROUND Although risk stratification is an important goal of cardiac noninvasive tests (NITs), few contemporary data exist on the prognostic value of different NITs according to patient sex. OBJECTIVES The goal of this study was to compare the results and prognostic information derived from anatomic versus stress testing in stable men and women with suspected coronary artery disease. METHODS In 8,966 patients tested at randomization (4,500 to computed tomography angiography [CTA], 52% female; 4,466 to stress testing, 53% female), we assessed the relationship between sex and NIT results and between sex and a composite of death, myocardial infarction, or unstable angina hospitalization. RESULTS In women, a positive CTA (>= 70% stenosis) was less likely than a positive stress test result (8% vs. 12%; adjusted odds ratio: 0.67). Compared with negative test results, a positive CTA was more strongly associated with subsequent clinical events than a positive stress test result (CTA-adjusted hazard ratio of 5.86 vs. stress-adjusted hazard ratio of 2.27; adjusted p = 0.028). Men were more likely to have a positive CTA than a positive stress test result (16% vs. 14%; adjusted odds ratio: 1.23). Compared with negative test results, a positive CTA was less strongly associated with subsequent clinical events than a positive stress test result in men, although this difference was not statistically significant (adjusted p = 0.168). Negative CTA and stress test results were equally likely to predict an event in both sexes. A significant interaction between sex, NIT type, and test result (p = 0.01) suggests that sex and NIT type jointly influence the relationship between test result and clinical events. CONCLUSIONS The prognostic value of an NIT result varies according to test type and patient sex. Women seem to derive more prognostic information from a CTA, whereas men tend to derive similar prognostic value from both test types. (C) 2016 by the American College of Cardiology Foundation. C1 [Pagidipati, Neha J.; Hemal, Kshipra; Coles, Adrian; Mark, Daniel B.; Dolor, Rowena J.; Daubert, Melissa A.; Shah, Svati H.; Martinez, Beth; Lee, Kerry L.; Douglas, Pamela S.] Duke Univ, Sch Med, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. [Dolor, Rowena J.; Shah, Svati H.] Duke Univ, Sch Med, Dept Med, Durham, NC 27715 USA. [Pellikka, Patricia A.] Mayo Clin, Rochester, MN USA. [Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Litwin, Sheldon E.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Udelson, James] Tufts Univ, Sch Med, Tufts Med Ctr, Boston, MA 02111 USA. RP Pagidipati, NJ (reprint author), Duke Univ, Sch Med, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM neha.pagidipati@dm.duke.edu FU National Heart, Lung, and Blood Institute [R01HL098237, R01HL098236, R01HL98305, R01HL098235]; Medtronic; CardioDx; St. Jude Medical; Eli Lilly; Bristol-Myers Squibb; Gilead Sciences; AGA Medical; Merck; Oxygen Biotherapeutics; AstraZeneca; Siemens Healthcare; HeartFlow FX From the aDuke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina; bDepartment of Medicine, Duke University School of Medicine, Durham, North Carolina; cMayo Clinic, Rochester, Minnesota; dMassachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; eDepartment of Medicine, Medical University of South Carolina, Charleston, South Carolina; and the fTufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts. This project was supported by grants from the National Heart, Lung, and Blood Institute (R01HL098237, R01HL098236, R01HL98305, and R01HL098235). This paper does not necessarily represent the official views of the National Heart, Lung, and Blood Institute. Dr. Mark has received personal fees from Medtronic, CardioDx, and St. Jude Medical; and grant support from Eli Lilly, Bristol-Myers Squibb, Gilead Sciences, AGA Medical, Merck, Oxygen Biotherapeutics, and AstraZeneca. Dr. Hoffmann has received grant support from Siemens Healthcare and HeartFlow. Dr. Douglas has received grant support from HeartFlow; and serves on a Data and Safety Monitoring Board for GE Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 21 TC 6 Z9 6 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN 7 PY 2016 VL 67 IS 22 BP 2607 EP 2616 DI 10.1016/j.jacc.2016.03.523 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DN7QF UT WOS:000377271300007 PM 27058908 ER PT J AU Yang, DR Wong, WP AF Yang, Darren Wong, Wesley P. TI Small but Mighty: Nanoparticles Probe Cellular Signaling Pathways SO DEVELOPMENTAL CELL LA English DT Editorial Material ID NOTCH; FORCE; ACTIVATION AB Mechanical forces play key roles in regulating cellular pathways but are challenging to study using standard biological approaches. In a recent issue of Cell, Seo et al. (2016) present a platform for in vivo single-molecule manipulation, using magnetoplasmonic nanoparticles capable of imaging, localizing, and force-loading receptor proteins at high spatiotemporal resolution. C1 [Yang, Darren; Wong, Wesley P.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Yang, Darren; Wong, Wesley P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Wong, Wesley P.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. RP Wong, WP (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.; Wong, WP (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.; Wong, WP (reprint author), Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. EM wesley.wong@childrens.harvard.edu FU NIGMS NIH HHS [R21 GM107907] NR 10 TC 1 Z9 1 U1 2 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 EI 1878-1551 J9 DEV CELL JI Dev. Cell PD JUN 6 PY 2016 VL 37 IS 5 BP 397 EP 398 DI 10.1016/j.devcel.2016.05.021 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA DN9OC UT WOS:000377408100006 PM 27270039 ER PT J AU Wang, ZW Young, MRI AF Wang, Zhewu Young, M. Rita I. TI PTSD, a Disorder with an Immunological Component SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE cytokines; immune regulation; inflammation; plasma; post-traumatic stress disorder ID POSTTRAUMATIC-STRESS-DISORDER; T-LYMPHOCYTE FUNCTION; QUALITY-OF-LIFE; EXOGENOUS SEROTONIN; GENE-EXPRESSION; CYTOKINE LEVELS; VETERANS; IMMUNE; BRAIN; INTERLEUKIN-6 AB Post-traumatic stress disorder (PTSD) has been associated with an inflammatory state. However, few studies have addressed the mechanisms underlying this immune imbalance that favors inflammation or how this imbalance contributes to PTSD. Whether the immune imbalance influences responsiveness or unresponsiveness of patients to PTSD treatments is currently not known. This review brings forward an immune emphasis to a mental health disorder that is unprecedented in its prevalence among combat Veterans of the ongoing conflicts in Iraq and Afghanistan and which also afflicts civilians who have undergone extreme traumatic experiences, such as following natural disasters, serious accidents, or assaults. Included is an overview of the correlative associations in human subjects between PTSD and inflammation and studies in animal models of PTSD, demonstrating causal contributions of inflammation and immune dysregulation to PTSD-like behavior following stress exposure. C1 [Wang, Zhewu] Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. [Wang, Zhewu] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Young, M. Rita I.] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA. [Young, M. Rita I.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. RP Young, MRI (reprint author), Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA.; Young, MRI (reprint author), Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. EM rita.young@va.gov FU Clinical Sciences Research and Development Program of the Department of Veterans Affairs [I01 CX000851, 1 I01 CX000487] FX This work was supported by the Clinical Sciences Research and Development Program of the Department of Veterans Affairs (Merit Review grants I01 CX000851 to MY and 1 I01 CX000487 to ZW). NR 66 TC 1 Z9 1 U1 8 U2 11 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PD JUN 6 PY 2016 VL 7 AR 219 DI 10.3389/fimmu.2016.00219 PG 6 WC Immunology SC Immunology GA DN4TX UT WOS:000377061200002 PM 27375619 ER PT J AU Weng, LD Song, W Jacobs, DJ Elliott, GD AF Weng, Lindong Song, Wei Jacobs, Donald J. Elliott, Gloria D. TI Molecular insights into water vapor absorption by aqueous lithium bromide and lithium bromide/sodium formate solutions SO APPLIED THERMAL ENGINEERING LA English DT Article DE Lithium bromide; Sodium formate; Liquid desiccant; Absorption refrigeration; Molecular dynamics simulation ID OF-THE-ART; THERMODYNAMIC PROPERTIES; LIQUID/VAPOR INTERFACE; DYNAMICS; SIMULATIONS; SYSTEMS; TEMPERATURE; PRESSURES; ABSORBENT; DENSITIES AB Aqueous lithium bromide (LiBr) solutions are commonly-employed as liquid desiccants, largely due to their low water vapor pressure at concentrations suitable for applications such as absorption refrigeration. However, LiBr-based desiccants have drawbacks such as corrosivity, crystallization at high concentrations, and high energy inputs to regenerate the absorbent. It was recently shown that adding formate salts (e.g., NaCOOH) into the LiBr + H2O mixture could mitigate disadvantages while maintaining most advantages, but these experimental findings were unable to elucidate the driving forces at the molecular level. Detailed knowledge of the molecular interactions that underpin absorption phenomenon in both traditional and newly developed ternary working fluids (e.g., LiBr + NaCOOH + H2O) is still incomplete. The present molecular modeling study of water vapor absorption by LiBr and LiBr + NaCOOH investigated the water vapor absorption kinetics, enabling the analysis of ionic clustering and hydrogen-bonding characteristics. Molecular simulations of LiBr + H2O compositions demonstrated that increasing the LiBr concentration enhances the absorption rate while decreasing the liquid-vapor interfacial thickness of the LiBr + H2O layer. The most interesting finding was the strong interaction between Li+ and COOH- which may enable the ternary mixture to accommodate more water molecules as a result of Li+-COOH- clustering compared to compositions containing only LiBr and H2O. Despite an increase in water vapor absorption capacity it was found that adding NaCOOH decreased the water vapor absorption rate. Elucidating the molecular origin that affects the performance of liquid desiccants upon addition of formate salts is a first step toward the rational design of new working fluids for liquid desiccant-related applications. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Weng, Lindong; Elliott, Gloria D.] Univ N Carolina, Dept Mech Engn & Engn Sci, Charlotte, NC 28223 USA. [Song, Wei; Jacobs, Donald J.] Univ N Carolina, Dept Phys & Opt Sci, Charlotte, NC 28223 USA. [Weng, Lindong] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02129 USA. [Song, Wei] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. RP Elliott, GD (reprint author), Univ N Carolina, Dept Mech Engn & Engn Sci, Charlotte, NC 28223 USA. EM gdelliot@uncc.edu RI Weng, Lindong/A-6041-2017 OI Weng, Lindong/0000-0003-4811-6531 NR 23 TC 0 Z9 0 U1 6 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-4311 J9 APPL THERM ENG JI Appl. Therm. Eng. PD JUN 5 PY 2016 VL 102 BP 125 EP 133 DI 10.1016/j.applthermaleng.2016.03.153 PG 9 WC Thermodynamics; Energy & Fuels; Engineering, Mechanical; Mechanics SC Thermodynamics; Energy & Fuels; Engineering; Mechanics GA DQ5UJ UT WOS:000379270300014 ER PT J AU Saadatpour, A Albert, R AF Saadatpour, Assieh Albert, Reka TI A comparative study of qualitative and quantitative dynamic models of biological regulatory networks SO EPJ NONLINEAR BIOMEDICAL PHYSICS LA English DT Article DE Dynamic models; Boolean models; Piecewise affine differential equations models; Hill-type models; Network motifs; Biological regulatory networks ID GRANULAR LYMPHOCYTE LEUKEMIA; PIECEWISE-LINEAR MODELS; DIFFERENTIAL-EQUATIONS; BOOLEAN NETWORKS; SACCHAROMYCES-CEREVISIAE; NEGATIVE FEEDBACK; GENETIC-CONTROL; SIMULATION; CIRCUITS; LOGIC AB Background: Mathematical modeling of biological regulatory networks provides valuable insights into the structural and dynamical properties of the underlying systems. While dynamic models based on differential equations provide quantitative information on the biological systems, qualitative models that rely on the logical interactions among the components provide coarse-grained descriptions useful for systems whose mechanistic underpinnings remain incompletely understood. The middle ground class of piecewise affine differential equation models was proven informative for systems with partial knowledge of kinetic parameters. Methods: In this work we provide a comparison of the dynamic characteristics of these three approaches applied on several biological regulatory network motifs. Specifically, we compare the attractors and state transitions in asynchronous Boolean, piecewise affine and Hill-type continuous models. Results: Our study shows that while the fixed points of asynchronous Boolean models are observed in continuous Hill-type and piecewise affine models, these models may exhibit different attractors under certain conditions. Conclusions: Overall, qualitative models are suitable for systems with limited knowledge of quantitative information. On the other hand, when practical, using quantitative models can provide detailed information about additional real-valued attractors not present in the qualitative models. C1 [Saadatpour, Assieh; Albert, Reka] Penn State Univ, Dept Phys, 104 Davey Lab, University Pk, PA 16802 USA. [Albert, Reka] Penn State Univ, Dept Biol, 104 Davey Lab, University Pk, PA 16802 USA. [Saadatpour, Assieh] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Saadatpour, Assieh] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. RP Albert, R (reprint author), Penn State Univ, Dept Phys, 104 Davey Lab, University Pk, PA 16802 USA.; Albert, R (reprint author), Penn State Univ, Dept Biol, 104 Davey Lab, University Pk, PA 16802 USA. EM rza1@psu.edu RI Albert, Reka/E-2195-2011 OI Albert, Reka/0000-0002-9485-0828 NR 72 TC 2 Z9 2 U1 0 U2 5 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 2195-0008 J9 EPJ NONLINEAR BIOMED JI EPJ Nonlinear Biomed. Phys. PD JUN 4 PY 2016 VL 4 AR 5 DI 10.1140/epjnbp/s40366-016-0031-y PG 13 WC Biophysics SC Biophysics GA DN4XI UT WOS:000377070100001 ER PT J AU Xing, FX Prince, JL Landman, BA AF Xing, Fangxu Prince, Jerry L. Landman, Bennett A. TI Investigation of Bias in Continuous Medical Image Label Fusion SO PLOS ONE LA English DT Article ID SEGMENTATION; VALIDATION; ALGORITHMS AB Image labeling is essential for analyzing morphometric features in medical imaging data. Labels can be obtained by either human interaction or automated segmentation algorithms, both of which suffer from errors. The Simultaneous Truth and Performance Level Estimation (STAPLE) algorithm for both discrete-valued and continuous-valued labels has been proposed to find the consensus fusion while simultaneously estimating rater performance. In this paper, we first show that the previously reported continuous STAPLE in which bias and variance are used to represent rater performance yields a maximum likelihood solution in which bias is indeterminate. We then analyze the major cause of the deficiency and evaluate two classes of auxiliary bias estimation processes, one that estimates the bias as part of the algorithm initialization and the other that uses a maximum a posteriori criterion with a priori probabilities on the rater bias. We compare the efficacy of six methods, three variants from each class, in simulations and through empirical human rater experiments. We comment on their properties, identify deficient methods, and propose effective methods as solution. C1 [Xing, Fangxu] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Prince, Jerry L.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. [Prince, Jerry L.; Landman, Bennett A.] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA. [Landman, Bennett A.] Vanderbilt Univ, Dept Elect Engn, Nashville, TN 37235 USA. RP Xing, FX (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM fxing1@mgh.harvard.edu FU National Institute of Neurological Disorders and Stroke [1R01NS056307, 1R21NS064534] FX This project was supported by National Institute of Neurological Disorders and Stroke grants 1R01NS056307 and 1R21NS064534 (http://www.ninds.nih.gov/). The author who received the funding is BL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 0 Z9 0 U1 2 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 JUN 3 PY 2016 VL 11 IS 6 AR e0155862 DI 10.1371/journal.pone.0155862 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DN8ZV UT WOS:000377369700023 PM 27258158 ER PT J AU Miller, K Cortes, J Hurvitz, SA Krop, IE Tripathy, D Verma, S Riahi, K Reynolds, JG Wickham, TJ Molnar, I Yardley, DA AF Miller, Kathy Cortes, Javier Hurvitz, Sara A. Krop, Ian E. Tripathy, Debu Verma, Sunil Riahi, Kaveh Reynolds, Joseph G. Wickham, Thomas J. Molnar, Istvan Yardley, Denise A. TI HERMIONE: a randomized Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician's choice plus trastuzumab in patients with previously treated, anthracycline-naive, HER2-positive, locally advanced/metastatic breast cancer SO BMC CANCER LA English DT Article DE Advanced/metastatic breast cancer; Antibody-conjugate; Doxorubicin; Cardiotoxicity; HERMIONE; Human epidermal growth factor receptor 2/HER2/Erb2; HER2-targeted liposomal doxorubicin; Immunoliposome; MM302; Trastuzumab ID PEGYLATED LIPOSOMAL DOXORUBICIN; INTERNATIONAL CONSENSUS GUIDELINES; III TRIAL; OBSERVATIONAL TRIAL; SURVIVAL ANALYSIS; THERAPY; CARDIOTOXICITY; DOCETAXEL; PROGRESSION; PERTUZUMAB AB Background: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is a particularly aggressive form of the disease, and ultimately progresses in patients with metastases on standard therapies. Anthracyclines, such as doxorubicin, are an effective treatment for HER2-positive breast cancer, particularly when administered in combination with trastuzumab - however, doxorubicin-related cardiotoxicity has limited its use. Many patients are therefore never treated with anthracyclines, even upon disease progression, despite the potential for benefit. MM-302 is a novel, HER2-targeted antibody-liposomal doxorubicin conjugate that specifically targets HER2overexpressing cells. Preclinical and Phase 1 data suggest that MM-302, as a monotherapy or in combination with trastuzumab, could be effective for managing previously treated, anthracycline-naive, HER2-positive breast cancer, without the cardiotoxicity observed with free doxorubicin formulations. Methods/Design: HERMIONE is an open-label, multicenter, randomized (1: 1) Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician's choice (gemcitabine, capecitabine, or vinorelbine) plus trastuzumab planned to enroll 250 anthracycline-naive patients with locally advanced/metastatic HER2-positive breast cancer. Key inclusion criteria are: previous treatment with trastuzumab (with or without pertuzumab) in any setting; refractory or intolerant to pertuzumab (refractory to pertuzumab defined as progression in the locally advanced or metastatic setting, or disease recurrence during or within 12 months of completing pertuzumab-containing neoadjuvant and/or adjuvant therapy); and disease progression on, or intolerant to, ado-trastuzumab emtansine for locally advanced or metastatic disease. The trial is currently being conducted at sites in the USA, Canada, and Western Europe. Treatment will be administered in 21-day cycles, and will be continued until disease progression or unacceptable toxicity. The primary endpoint is independently assessed progression-free survival (PFS). Tumor response will be assessed every 6 weeks, and defined according to RECIST v1.1. Secondary endpoints include investigator-assessed PFS, overall survival (OS), OS rates at 6 months and 1 year, objective response rates, safety and tolerability, quality of life, and the pharmacokinetic profile of MM-302 plus trastuzumab. Discussion: The HERMIONE study will evaluate the efficacy and safety of MM-302 plus trastuzumab in patients with refractory HER2-positive advanced/metastatic breast cancer for whom there are no standard of care therapies with a proven survival advantage. C1 [Miller, Kathy] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. [Cortes, Javier] VHIO, Barcelona, Spain. [Cortes, Javier] Ramony Cajal Univ Hosp, Madrid, Spain. [Hurvitz, Sara A.] Univ Calif Los Angeles, Los Angeles, CA USA. [Krop, Ian E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tripathy, Debu] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Verma, Sunil] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Riahi, Kaveh; Reynolds, Joseph G.; Wickham, Thomas J.; Molnar, Istvan] Merrimack Pharmaceut Inc, 1 Kendall Sq,Suite B7201, Cambridge, MA 02139 USA. [Yardley, Denise A.] Sarah Cannon Res Inst, Nashville, TN USA. [Yardley, Denise A.] Tennessee Oncol PLLC, Nashville, TN USA. RP Reynolds, JG (reprint author), Merrimack Pharmaceut Inc, 1 Kendall Sq,Suite B7201, Cambridge, MA 02139 USA. EM jreynolds@merrimackpharma.com FU Merrimack Pharmaceuticals FX This study is commercially funded by Merrimack Pharmaceuticals. NR 51 TC 3 Z9 3 U1 3 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD JUN 3 PY 2016 VL 16 AR 352 DI 10.1186/s12885-016-2385-z PG 11 WC Oncology SC Oncology GA DN3LW UT WOS:000376964700001 PM 27259714 ER PT J AU Zhao, X Papadopoulos, A Ibusuki, S Bichara, DA Saris, DB Malda, J Anseth, KS Gill, TJ Randolph, MA AF Zhao, Xing Papadopoulos, Anestis Ibusuki, Shinichi Bichara, David A. Saris, Daniel B. Malda, Jos Anseth, Kristi S. Gill, Thomas J. Randolph, Mark A. TI Articular cartilage generation applying PEG-LA-DM/PEGDM copolymer hydrogels SO BMC MUSCULOSKELETAL DISORDERS LA English DT Article DE Cartilage regeneration; Articular cartilage; PEG hydrogel; PEGDM hydrogel ID AUTOLOGOUS CHONDROCYTE IMPLANTATION; EXTRACELLULAR-MATRIX PRODUCTION; TISSUE-ENGINEERED CARTILAGE; ENCAPSULATED CHONDROCYTES; POLY(ETHYLENE GLYCOL); ADHESIVE STRENGTH; FOLLOW-UP; IN-VITRO; REPAIR; OUTCOMES AB Background: Injuries to the human native cartilage tissue are particularly problematic because cartilage has little to no ability to heal or regenerate itself. Employing a tissue engineering strategy that combines suitable cell sources and biomimetic hydrogels could be a promising alternative to achieve cartilage regeneration. However, the weak mechanical properties may be the major drawback to use fully degradable hydrogels. Besides, most of the fully degradable hydrogels degrade too fast to permit enough extracellular matrix (ECM) production for neocartilage formation. In this study, we demonstrated the feasibility of neocartilage regeneration using swine articular chondrocytes photoencapsualted into poly (ethylene glycol) dimethacrylate (PEGDM) copolymer hydrogels composed of different degradation profiles: degradable (PEG-LA-DM) and nondegradable (PEGDM) macromers in molar ratios of 50/50, 60/40, 70/30, 80/20, and 90/10. Methods: Articular chondrocytes were isolated enzymatically from juvenile Yorkshire swine cartilage. 6 x 10(7) cells cells were added to each milliliter of macromer/photoinitiator (12959) solution. Nonpolymerized gel containing the cells (100 mu L) was placed in cylindrical molds (4.5 mm diameter x 6.5 mm in height). The macromer/photoinitiator/chondrocyte solutions were polymerized using ultraviolet (365 nm) light at 10 mW/cm(2) for 10 mins. Also, an articular cartilaginous ring model was used to examine the capacity of the engineered cartilage to integrate with native cartilage. Samples in the pilot study were collected at 6 weeks. Samples in the long-term experimental groups (60/40 and 70/30) were implanted into nude mice subcutaneously and harvested at 6, 12 and 18 weeks. Additionally, cylindrical constructs that were not implanted used as time zero controls. All of the harvested specimens were examined grossly and analyzed histologically and biochemically. Results: Histologically, the neocartilage formed in the photochemically crosslinked gels resembled native articular cartilage with chondrocytes in lacunae and surrounded by new ECM. Increases in total DNA, glycosaminoglycan, and hydroxyproline were observed over the time periods studied. The neocartilage integrated with existing native cartilag. Conclusions: Articular cartilage generation was achieved using swine articular chondrocytes photoencapsulated in copolymer PEGDM hydrogels, and the neocartilage tissue had the ability to integrate with existing adjacent native cartilage. C1 [Zhao, Xing; Papadopoulos, Anestis; Ibusuki, Shinichi; Bichara, David A.; Gill, Thomas J.; Randolph, Mark A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. [Zhao, Xing; Bichara, David A.; Randolph, Mark A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, WACC 435,15 Parkman St, Boston, MA 02114 USA. [Zhao, Xing; Saris, Daniel B.; Malda, Jos] Univ Med Ctr Utrecht, Dept Orthopaed, Utrecht, Netherlands. [Saris, Daniel B.] Univ Twente, MIRA Inst Biotechnol & Tech Med, POB 217, NL-7500 AE Enschede, Netherlands. [Malda, Jos] Univ Utrecht, Fac Vet Med, Dept Equine Sci, Utrecht, Netherlands. [Anseth, Kristi S.] Univ Colorado, Dept Chem & Biol Engn, Boulder, CO 80309 USA. RP Randolph, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA.; Randolph, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, WACC 435,15 Parkman St, Boston, MA 02114 USA. EM MARANDOLPH@mgh.harvard.edu FU National Institutes of Health [R01DE12998]; Plastic Surgery Educational Foundation FX The authors would like to thank Mitun Ranka for supporting in preparation and implantation of the constructs and Arthur Foubert for his great assistance during harvesting the donor animal tissues. This work was supported by grants from the National Institutes of Health (R01DE12998) and Plastic Surgery Educational Foundation. NR 46 TC 1 Z9 1 U1 11 U2 21 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2474 J9 BMC MUSCULOSKEL DIS JI BMC Musculoskelet. Disord. PD JUN 3 PY 2016 VL 17 AR 245 DI 10.1186/s12891-016-1100-1 PG 10 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA DN7IL UT WOS:000377248600001 PM 27255078 ER PT J AU Bucci, V Tzen, B Li, N Simmons, M Tanoue, T Bogart, E Deng, LX Yeliseyev, V Delaney, ML Liu, Q Olle, B Stein, RR Honda, K Bry, L Gerber, GK AF Bucci, Vanni Tzen, Belinda Li, Ning Simmons, Matt Tanoue, Takeshi Bogart, Elijah Deng, Luxue Yeliseyev, Vladimir Delaney, Mary L. Liu, Qing Olle, Bernat Stein, Richard R. Honda, Kenya Bry, Lynn Gerber, Georg K. TI MDSINE: Microbial Dynamical Systems INference Engine for microbiome time-series analyses SO GENOME BIOLOGY LA English DT Article ID HUMAN GUT MICROBIOME; INTESTINAL BACTERIA; ESCHERICHIA-COLI; GENE; BIOSYNTHESIS; MENAQUINONE; EXPRESSION; STRAIN; LASSO; ACID AB Predicting dynamics of host-microbial ecosystems is crucial for the rational design of bacteriotherapies. We present MDSINE, a suite of algorithms for inferring dynamical systems models from microbiome time-series data and predicting temporal behaviors. Using simulated data, we demonstrate that MDSINE significantly outperforms the existing inference method. We then show MDSINE's utility on two new gnotobiotic mice datasets, investigating infection with Clostridium difficile and an immune-modulatory probiotic. Using these datasets, we demonstrate new capabilities, including accurate forecasting of microbial dynamics, prediction of stable sub-communities that inhibit pathogen growth, and identification of bacteria most crucial to community integrity in response to perturbations. C1 [Bucci, Vanni; Simmons, Matt] Univ Massachusetts Dartmouth, Dept Biol, Program Biotechnol & Biomed Engn, 285 Old Westport Rd, N Dartmouth, MA 02747 USA. [Tzen, Belinda; Li, Ning; Bogart, Elijah; Deng, Luxue; Yeliseyev, Vladimir; Delaney, Mary L.; Liu, Qing; Bry, Lynn; Gerber, Georg K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Massachusetts Host Microbiome Ctr,Dept Pathol, 221 Longwood Ave, Boston, MA 02115 USA. [Tanoue, Takeshi; Honda, Kenya] RIKEN Ctr Integrat Med Sci IMS, Yokohama, Kanagawa 2300045, Japan. [Olle, Bernat] Vedanta Biosc, 501 Boylston St,Suite 6102, Boston, MA 02116 USA. [Stein, Richard R.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02215 USA. RP Bucci, V (reprint author), Univ Massachusetts Dartmouth, Dept Biol, Program Biotechnol & Biomed Engn, 285 Old Westport Rd, N Dartmouth, MA 02747 USA.; Gerber, GK (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Massachusetts Host Microbiome Ctr,Dept Pathol, 221 Longwood Ave, Boston, MA 02115 USA. EM vanni.bucci@umassd.edu; ggerber@bwh.harvard.edu FU Defense Advanced Projects Agency Biological Robustness in Complex Settings program (DARPA BRICS) [HR0011-15-C-0094]; Harvard Digestive Diseases Center [P30DK034854]; National Heart, Lung and Blood Institute [2T32HL007627-31]; National Institute of Allergy and Infectious Disease [R15-AI112985-01A1]; National Science Foundation [1458347]; Brigham and Women's Hospital Department of Pathology FX This work was supported by the Defense Advanced Projects Agency Biological Robustness in Complex Settings program (DARPA BRICS award HR0011-15-C-0094) and grants from the Harvard Digestive Diseases Center (Pilot and Feasibility Grant to GKG and Core Grant to LB, under NIH Grant P30DK034854), the National Heart, Lung and Blood Institute (grant 2T32HL007627-31 supporting EB), the National Institute of Allergy and Infectious Disease (grant R15-AI112985-01A1 supporting VB), and the National Science Foundation (grant 1458347 supporting VB). GKG also acknowledges support from the Brigham and Women's Hospital Department of Pathology. NR 55 TC 2 Z9 3 U1 6 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PD JUN 3 PY 2016 VL 17 AR 121 DI 10.1186/s13059-016-0980-6 PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA DN7TL UT WOS:000377281800003 PM 27259475 ER PT J AU Gallegos, LL Ng, MR Sowa, ME Selfors, LM White, A Zervantonakis, IK Singh, P Dhakal, S Harper, JW Brugge, JS AF Gallegos, Lisa Leon Ng, Mei Rosa Sowa, Mathew E. Selfors, Laura M. White, Anne Zervantonakis, Ioannis K. Singh, Pragya Dhakal, Sabin Harper, J. Wade Brugge, Joan S. TI A protein interaction map for cell-cell adhesion regulators identifies DUSP23 as a novel phosphatase for beta-catenin SO SCIENTIFIC REPORTS LA English DT Article ID E-CADHERIN; ADHERENS JUNCTIONS; TYROSINE PHOSPHORYLATION; ALPHA-CATENIN; MIGRATION; CYTOSKELETON; EXPRESSION; MOLECULES; VINCULIN; KINASES AB Cell-cell adhesion is central to morphogenesis and maintenance of epithelial cell state. We previously identified 27 candidate cell-cell adhesion regulatory proteins (CCARPs) whose down-regulation disrupts epithelial cell-cell adhesion during collective migration. Using a protein interaction mapping strategy, we found that 18 CCARPs link to core components of adherens junctions or desmosomes. We further mapped linkages between the CCARPs and other known cell-cell adhesion proteins, including hits from recent screens uncovering novel components of E-cadherin adhesions. Mechanistic studies of one novel CCARP which links to multiple cell-cell adhesion proteins, the phosphatase DUSP23, revealed that it promotes dephosphorylation of beta-catenin at Tyr 142 and enhances the interaction between alpha-and beta-catenin. DUSP23 knockdown specifically diminished adhesion to E-cadherin without altering adhesion to fibronectin matrix proteins. Furthermore, DUSP23 knockdown produced "zipper-like" cell-cell adhesions, caused defects in transmission of polarization cues, and reduced coordination during collective migration. Thus, this study identifies multiple novel connections between proteins that regulate cell-cell interactions and provides evidence for a previously unrecognized role for DUSP23 in regulating E-cadherin adherens junctions through promoting the dephosphorylation of beta-catenin. C1 [Gallegos, Lisa Leon; Ng, Mei Rosa; Sowa, Mathew E.; Selfors, Laura M.; White, Anne; Zervantonakis, Ioannis K.; Singh, Pragya; Dhakal, Sabin; Harper, J. Wade; Brugge, Joan S.] Harvard Univ, Sch Med, Cell Biol, Boston, MA USA. [Ng, Mei Rosa] Massachusetts Gen Hosp, Radiat Oncol, Boston, MA 02114 USA. [Sowa, Mathew E.] Warp Drive Bio LLC, Cambridge, MA USA. RP Brugge, JS (reprint author), Harvard Univ, Sch Med, Cell Biol, Boston, MA USA. EM joan_brugge@hms.harvard.edu FU Susan G. Komen for the Cure Foundation [SAC130057, KG111465]; Cell Migration Consortium/National Institutes of Health [GM064346]; National Institutes of Health [AG011085] FX We thank Jennifer Waters, Talley Lambert, and Lauren Alvarenga at the Nikon Imaging Center at Harvard Medical School for microscopy study support; Marc Vidal and the hOrfeome database for clones; Kaylene Simpson for identifying the genes with the dissociator phenotype and for helpful discussions; Ghassan Mouneimne, Marcin Iwanicki, Jon Coloff and other members of the Brugge laboratory for training and helpful discussions; Eric Bennett, Sebastian Hayes, John Lydeard, and other members of the Harper laboratory for mass spectrometry support; Chueh-Ling Kuo for equipment training, and Angie Martinez Gakidis for editing the manuscript. HEK293 cells stably expressing Fc-E-cadherin were a generous gift from Jonathan Higgins. These studies were supported by grants from the Susan G. Komen for the Cure Foundation to JSB (SAC130057) and LLG (KG111465), the Cell Migration Consortium/National Institutes of Health (GM064346) to JSB, and National Institutes of Health (AG011085) to JWH. NR 44 TC 0 Z9 0 U1 4 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JUN 3 PY 2016 VL 6 AR 27114 DI 10.1038/srep27114 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DN3YH UT WOS:000376999700002 PM 27255161 ER PT J AU Zanoni, I Tan, YH Di Gioia, M Broggi, A Ruan, JB Shi, JJ Donado, CA Shao, F Wu, H Springstead, JR Kagan, JC AF Zanoni, Ivan Tan, Yunhao Di Gioia, Marco Broggi, Achille Ruan, Jianbin Shi, Jianjin Donado, Carlos A. Shao, Feng Wu, Hao Springstead, James R. Kagan, Jonathan C. TI An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells SO SCIENCE LA English DT Article ID INFLAMMATORY CASPASES; OXIDIZED PHOSPHOLIPIDS; IMMUNE-SYSTEM; DANGER; ACTIVATION; PROTECTS; FAMILY; DEATH; LPS AB Dendritic cells (DCs) use pattern recognition receptors to detect microorganisms and activate protective immunity. These cells and receptors are thought to operate in an all-or-nothing manner, existing in an immunologically active or inactive state. Here, we report that encounters with microbial products and self-encoded oxidized phospholipids (oxPAPC) induce an enhanced DC activation state, which we call "hyperactive." Hyperactive DCs induce potent adaptive immune responses and are elicited by caspase-11, an enzyme that binds oxPAPC and bacterial lipopolysaccharide (LPS). oxPAPC and LPS bind caspase-11 via distinct domains and elicit different inflammasome-dependent activities. Both lipids induce caspase-11-dependent interleukin-1 release, but only LPS induces pyroptosis. The cells and receptors of the innate immune system can therefore achieve different activation states, which may permit context-dependent responses to infection. C1 [Zanoni, Ivan; Tan, Yunhao; Di Gioia, Marco; Broggi, Achille; Donado, Carlos A.; Kagan, Jonathan C.] Harvard Univ, Sch Med, Boston, MA USA. [Zanoni, Ivan; Tan, Yunhao; Di Gioia, Marco; Broggi, Achille; Donado, Carlos A.; Kagan, Jonathan C.] Boston Childrens Hosp, Div Gastroenterol, Boston, MA USA. [Zanoni, Ivan] Univ Milano Bicocca, Dept Biotechnol & Biosci, Milan, Italy. [Zanoni, Ivan] Humanitas Clin & Res Ctr, Unit Cell Signalling & Innate Immun, Milan, Italy. [Springstead, James R.] Western Michigan Univ, Dept Chem & Paper Engn, Kalamazoo, MI 49008 USA. [Shi, Jianjin; Shao, Feng] Natl Inst Biol Sci, Beijing 102206, Peoples R China. [Ruan, Jianbin; Wu, Hao] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Wu, Hao] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. RP Kagan, JC (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Kagan, JC (reprint author), Boston Childrens Hosp, Div Gastroenterol, Boston, MA USA. EM jonathan.kagan@childrens.harvard.edu RI Tan, Yunhao/K-7442-2016; OI Tan, Yunhao/0000-0002-5516-4980; Shi, Jianjin/0000-0001-8048-5180 FU NIH [AI093589, AI072955, P30 DK34854, 1R15HL121770-01A1, 1R01AI121066-01A1]; Burroughs Wellcome Fund; Harvard Digestive Diseases Center [P30 DK34854]; Cariplo Foundation; Jane Coffin Childs Fund FX We thank members of the Kagan laboratory for helpful discussions. The results reported in this manuscript are tabulated in the main paper and in the supplementary materials. J.C.K. and Boston Children's Hospital have filed an international patent application (PCT/US2016/012994) that relates to the adjuvant activity of oxPAPC. J.C.K. is supported by NIH grants AI093589, AI072955, and P30 DK34854 and a gift from Mead Johnson & Company. J.C.K. holds an Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund. I.Z. is supported by NIH grant 1R01AI121066-01A1, Harvard Digestive Diseases Center grant P30 DK34854, and the Cariplo Foundation. Y.T. is supported by a fellowship of the Jane Coffin Childs Fund (Merck Fellow). J.S. is supported by NIH grant 1R15HL121770-01A1. J.S. and F.S. performed the experiments in Fig. 3D but were not involved in the experimental design or interpretation of data. NR 23 TC 14 Z9 15 U1 8 U2 18 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 JUN 3 PY 2016 VL 352 IS 6290 BP 1232 EP 1236 DI 10.1126/science.aaf3036 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DN4NY UT WOS:000377045700046 PM 27103670 ER PT J AU Liu, TC Gurram, B Baldridge, MT Head, R Lam, V Luo, CW Cao, YM Simpson, P Hayward, M Holtz, ML Bousounis, P Noe, J Lerner, D Cabrera, J Biank, V Stephens, M Huttenhower, C McGovern, DPB Xavier, RJ Stappenbeck, TS Salzman, NH AF Liu, Ta-Chiang Gurram, Bhaskar Baldridge, Megan T. Head, Richard Vy Lam Luo, Chengwei Cao, Yumei Simpson, Pippa Hayward, Michael Holtz, Mary L. Bousounis, Pavlos Noe, Joshua Lerner, Diana Cabrera, Jose Biank, Vincent Stephens, Michael Huttenhower, Curtis McGovern, Dermot P. B. Xavier, Ramnik J. Stappenbeck, Thaddeus S. Salzman, Nita H. TI Paneth cell defects in Crohn's disease patients promote dysbiosis SO JCI INSIGHT LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; INTESTINAL INFLAMMATION; FECAL MICROBIOTA; GUT MICROBIOME; GENE ATG16L1; ER STRESS; ONSET; PHENOTYPES; DIVERSITY; MOUSE AB BACKGROUND. Paneth cell dysfunction has been implicated in a subset of Crohn's disease (CD) patients. We previously stratified clinical outcomes of CD patients by using Paneth cell phenotypes, which we defined by the intracellular distribution of antimicrobial proteins. Animal studies suggest that Paneth cells shape the intestinal microbiome. However, it is unclear whether Paneth cell phenotypes alter the microbiome complexity in CD subjects. Therefore, we analyzed the correlation of Paneth cell phenotypes with mucosal microbiome composition and ileal RNA expression in pediatric CD and noninflammatory bowel disease (non-IBD) patients. METHODS. Pediatric CD (n = 44) and non-IBD (n = 62) patients aged 4 to 18 were recruited prior to routine endoscopic biopsy. Ileal mucosal samples were analyzed for Paneth cell phenotypes, mucosal microbiome composition, and RNA transcriptome. RESULTS. The prevalence of abnormal Paneth cells was higher in pediatric versus adult CD cohorts. For pediatric CD patients, those with abnormal Paneth cells showed significant changes in their ileal mucosal microbiome, highlighted by reduced protective microbes and enriched proinflammatory microbes. Ileal transcriptome profiles showed reduced transcripts for genes that control oxidative phosphorylation in CD patients with abnormal Paneth cells. These transcriptional changes in turn were correlated with specific microbiome alterations. In non-IBD patients, a subset contained abnormal Paneth cells. However, this subset was not associated with alterations in the microbiome or host transcriptome. CONCLUSION. Paneth cell abnormalities in human subjects are associated with mucosal dysbiosis in the context of CD, and these changes are associated with alterations in oxidative phosphorylation, potentially in a feedback loop. C1 [Liu, Ta-Chiang; Baldridge, Megan T.; Stappenbeck, Thaddeus S.] Washington Univ, Dept Pathol & Immunol, St Louis, MO USA. [Gurram, Bhaskar; Vy Lam; Hayward, Michael; Holtz, Mary L.; Bousounis, Pavlos; Noe, Joshua; Lerner, Diana; Cabrera, Jose; Biank, Vincent; Stephens, Michael; Salzman, Nita H.] Med Coll Wisconsin, Dept Pediat, Div Gastroenterol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. [Head, Richard] Washington Univ, Genome Technol Access Ctr, St Louis, MO USA. [Luo, Chengwei; Huttenhower, Curtis; Xavier, Ramnik J.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Cao, Yumei; Simpson, Pippa] Med Coll Wisconsin, Dept Pediat, Div Quantitat Hlth Serv, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. [Huttenhower, Curtis] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [McGovern, Dermot P. B.] Cedars Sinai Med Ctr, F Widjaja Fdn Inflammatory Bowel & Immunobiol Res, Los Angeles, CA 90048 USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Salzman, NH (reprint author), 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.; Stappenbeck, TS (reprint author), 660 South Euclid Ave,Campus Box 8118, St Louis, MO 63110 USA. EM stappenb@pathology.wustl.edu; nsalzman@mcw.edu FU NIDDK NIH HHS [P30 DK043351] NR 62 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA SN 2379-3708 J9 JCI INSIGHT JI JCI Insight PD JUN 2 PY 2016 VL 1 IS 8 AR e86907 DI 10.1172/jci.insight.86907 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA EB1LB UT WOS:000387112100010 PM 27699268 ER PT J AU Madariaga, MLL Spencer, PJ Shanmugarajah, K Crisalli, KA Chang, DC Markmann, JF Elias, N Cosimi, AB Sachs, DH Kawai, T AF Madariaga, Maria Lucia L. Spencer, Philip J. Shanmugarajah, Kumaran Crisalli, Kerry A. Chang, David C. Markmann, James F. Elias, Nahel Cosimi, A. Benedict Sachs, David H. Kawai, Tatsuo TI Effect of tolerance versus chronic immunosuppression protocols on the quality of life of kidney transplant recipients SO JCI INSIGHT LA English DT Article ID HEMATOPOIETIC-CELL TRANSPLANTATION; STAGE RENAL-DISEASE; SUBCLINICAL NONCOMPLIANCE; BONE-MARROW; THERAPY; CONSEQUENCES; CHIMERISM; OUTCOMES; DRUGS; GRAFT AB BACKGROUND. Kidney transplant patients on tolerance protocols avoid the morbidity associated with the use of conventional chronic immunosuppressive regimens. However, the impact of tolerance versus conventional regimens on the quality of life (QOL) of kidney transplant patients is unknown. METHODS. Five patients who achieved long-term immunosuppression-free renal allograft survival after combined kidney and bone marrow transplantation (tolerant group) were compared with thirty-two comparable kidney transplant recipients on conventional immunosuppression (conventional group). QOL was compared with 16 conventional recipients using the Kidney Disease Quality of Life Short Form 36 (KDQOL SF-36) and the Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSD-59R). RESULTS. Patients in the tolerant group required significantly less treatment after transplant for hypertension and no medications for diabetes (P < 0.01). There was no incidence of diabetes, dyslipidemia, or malignancies in the tolerant group, while these were observed in 12.5%, 40.6%, and 11.8% of the conventional group, respectively. Tolerant patients experienced better overall health (P < 0.01) and scored higher on kidney transplant-targeted scales and healthy survey scales than patients in the conventional group according to the KDQOL SF-36 (P < 0.05). Tolerant patients were less likely to experience depression, dyspnea, excessive appetite/thirst, flatulence, hearing loss, itching, joint pain, lack of energy, muscle cramps, and lack of libido than conventional patients according to the MTSOSD-59R (P < 0.05). CONCLUSION. Kidney transplant recipients who achieved tolerance experience significantly fewer incidences of complications, improved QOL, and fewer comorbid symptoms compared with patients on conventional immunosuppression. These results support the expanded use of tolerance protocols in kidney transplantation. C1 [Madariaga, Maria Lucia L.; Spencer, Philip J.; Shanmugarajah, Kumaran; Crisalli, Kerry A.; Chang, David C.; Markmann, James F.; Elias, Nahel; Cosimi, A. Benedict; Sachs, David H.; Kawai, Tatsuo] Massachusetts Gen Hosp, Dept Surg, Ctr Transplantat Sci, Boston, MA 02114 USA. RP Madariaga, MLL (reprint author), Massachusetts Gen Hosp, GRB 4-425,55 Fruit St, Boston, MA 02114 USA. EM mmadariaga@partners.org NR 24 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA SN 2379-3708 J9 JCI INSIGHT JI JCI Insight PD JUN 2 PY 2016 VL 1 IS 8 AR e87019 DI 10.1172/jci.insight.87019 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA EB1LB UT WOS:000387112100013 ER PT J AU Schrag, D AF Schrag, Deborah TI Reimbursing Wisely? CMS's Trial of Medicare Part B Drug Payment Reform SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Schrag, D (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 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 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 2 PY 2016 VL 374 IS 22 BP 2101 EP 2105 DI 10.1056/NEJMp1603735 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA EB2RP UT WOS:000387209900001 PM 27248616 ER PT J AU Hsu, J AF Hsu, John TI The ACA and Risk Pools - Insurer Losses in the Setting of Noncompliant Plans SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Hsu, John] Massachusetts Gen Hosp, Mongan Inst Hlth Policy Ctr, Boston, MA 02114 USA. [Hsu, John] Harvard Med Sch, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Hsu, J (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy Ctr, Boston, MA 02114 USA.; Hsu, J (reprint author), Harvard Med Sch, Dept Hlth Care Policy, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 2 PY 2016 VL 374 IS 22 BP 2105 EP 2107 DI 10.1056/NEJMp1602981 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA EB2RP UT WOS:000387209900002 PM 27248617 ER PT J AU Fiore, LD Lavori, PW AF Fiore, Louis D. Lavori, Philip W. TI Integrating Randomized Comparative Effectiveness Research with Patient Care SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID CLINICAL-TRIAL; INFORMED-CONSENT; POINT; ATTITUDES C1 [Fiore, Louis D.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Dept Vet Affairs, VA Cooperat Studies Program, Boston, MA USA. [Lavori, Philip W.] Stanford Univ, Sch Med, Dept Biomed Data Sci, Stanford, CA 94305 USA. RP Lavori, PW (reprint author), Stanford Univ, Dept Hlth Res & Policy, HRP Redwood Bldg,259 Campus Dr, Stanford, CA 94305 USA. EM lavori@stanford.edu NR 10 TC 6 Z9 6 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 2 PY 2016 VL 374 IS 22 BP 2152 EP 2158 DI 10.1056/NEJMra1510057 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA EB2RP UT WOS:000387209900008 PM 27248620 ER PT J AU Roberts, AW Davids, MS Seymour, JF AF Roberts, Andrew W. Davids, Matthew S. Seymour, John F. TI New Agents to Treat Chronic Lymphocytic Leukemia REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Roberts, Andrew W.] Royal Melbourne Hosp, Parkville, Vic, Australia. [Davids, Matthew S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Seymour, John F.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. RP Roberts, AW (reprint author), Royal Melbourne Hosp, Parkville, Vic, Australia. EM andrew.roberts@mh.org.au RI Roberts, Andrew/C-6736-2012 OI Roberts, Andrew/0000-0002-7341-5720 NR 2 TC 0 Z9 0 U1 2 U2 3 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 JUN 2 PY 2016 VL 374 IS 22 BP 2186 EP 2187 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA EB2RP UT WOS:000387209900023 PM 27248631 ER PT J AU Walter, JE Armanios, M AF Walter, Jolan E. Armanios, Mary TI Case 41-2015: A Boy with Immune and Liver Abnormalities REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID DYSKERATOSIS-CONGENITA; TELOMERES; MUTATIONS C1 [Walter, Jolan E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Armanios, Mary] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. RP Walter, JE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 2 PY 2016 VL 374 IS 22 BP 2193 EP 2193 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA EB2RP UT WOS:000387209900035 PM 27248644 ER PT J AU Goldenberg, RL Thorsten, VR Althabe, F Saleem, S Garces, A Carlo, WA Pasha, O Chomba, E Goudar, S Esamai, F Krebs, NF Derman, RJ Liechty, EA Patel, A Hibberd, PL Buekens, PM Koso-Thomas, M Miodovnik, M Jobe, AH Wallace, DD Belizan, JM McClure, EM AF Goldenberg, Robert L. Thorsten, Vanessa R. Althabe, Fernando Saleem, Sarah Garces, Ana Carlo, Waldemar A. Pasha, Omrana Chomba, Elwyn Goudar, Shivaprasad Esamai, Fabian Krebs, Nancy F. Derman, Richard J. Liechty, Edward A. Patel, Archana Hibberd, Patricia L. Buekens, Pierre M. Koso-Thomas, Marion Miodovnik, Menachem Jobe, Alan H. Wallace, Dennis D. Belizan, Jose M. McClure, Elizabeth M. TI The global network antenatal corticosteroids trial: impact on stillbirth SO REPRODUCTIVE HEALTH LA English DT Article ID MIDDLE-INCOME COUNTRIES; PRETERM BIRTH; NEONATAL DEATH; RISK; MULTICOUNTRY; PREGNANCY; WOMEN AB Background: Antenatal corticosteroids are commonly used to reduce neonatal mortality, but most research to date has been in high-resource settings and few studies have evaluated its impact on stillbirth. In the Antenatal Corticosteroids Trial (ACT), a multi-country trial to assess impact of a multi-faceted intervention including antenatal corticosteroids to reduce neonatal mortality associated with preterm birth, we found an overall increase in 28-day neonatal mortality and stillbirth associated with the intervention. Methods: The ACT was a cluster-randomized trial conducted in 102 clusters across 7 research sites in 6 countries (India [ 2 sites], Pakistan, Zambia, Kenya, Guatemala and Argentina), comparing an intervention to train birth attendants at all levels of the health system to identify women at risk of preterm birth, administer corticosteroids and refer women at risk. Because of inadequate gestational age dating, the <5th percentile birth weight was used as a proxy for preterm birth. A pre-specified secondary outcome of the trial was stillbirth. Results: After adjusting for the pre-trial imbalance in stillbirth rates, the ACT intervention was associated with a non-significant increased risk of stillbirth (aRR 1.08, 95 % CI, 0.99-1.17, p-0.073). Additionally, the stillbirth rate was higher in the term births (1.20 95 % CI 1.06-1.37, 0.004) and among those with signs of maceration (RR 1.18 (1.04-1.35), p = 0.013) in the intervention vs. control clusters. Differences in obstetric care favored the control clusters and maternal infection was likely more common in the intervention clusters. Conclusions: In this pragmatic trial, limited data were available to identify the causes of the increase in stillbirths in the intervention clusters. A higher rate of stillbirth in the intervention clusters prior to the trial, differences in obstetric care and an increase in maternal infection are potential explanations for the observed increase in stillbirths in the intervention clusters during the trial. C1 [Goldenberg, Robert L.; Saleem, Sarah] Columbia Univ, New York, NY USA. [Thorsten, Vanessa R.; Wallace, Dennis D.; McClure, Elizabeth M.] RTI Int, Durham, NC USA. [Althabe, Fernando; Belizan, Jose M.] IECS, Buenos Aires, DF, Argentina. [Saleem, Sarah; Pasha, Omrana] Aga Khan Univ, Karachi, Pakistan. [Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA. [Chomba, Elwyn] Univ Teaching Hosp, Lusaka, Zambia. [Goudar, Shivaprasad] KLE Univ JN Med Coll, Belgaum, India. [Esamai, Fabian] Moi Univ, Eldoret, Kenya. [Krebs, Nancy F.] Univ Colorado, Sch Med, Denver, CO USA. [Derman, Richard J.] Christiana Care, Newark, DE USA. [Liechty, Edward A.] Indiana Univ, Indianapolis, IN 46204 USA. [Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India. [Hibberd, Patricia L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Buekens, Pierre M.] Tulane Sch Publ Hlth & Trop Med, New Orleans, LA USA. [Koso-Thomas, Marion; Miodovnik, Menachem] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Jobe, Alan H.] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Goldenberg, Robert L.] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. RP Goldenberg, RL (reprint author), Columbia Univ, New York, NY USA.; Goldenberg, RL (reprint author), Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. EM rlg@columbia.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01 HD058322, U01 HD040477, U01 HD043464, U01 HD040657, U01 HD042372, U01 HD040607, U01 HD058326, U01 HD040636]; Bill and Melinda Gates Foundation FX This trial was funded through grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (U01 HD058322, U01 HD040477, U01 HD043464, U01 HD040657, U01 HD042372, U01 HD040607, U01 HD058326, U01 HD040636). Additional support was also provided by the Bill and Melinda Gates Foundation (FA, KK, JMB) NR 13 TC 0 Z9 0 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4755 J9 REPROD HEALTH JI Reprod. Health PD JUN 2 PY 2016 VL 13 AR 68 DI 10.1186/s12978-016-0174-4 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DP6OU UT WOS:000378617300001 PM 27255082 ER PT J AU Emile, JF Abla, O Fraitag, S Horne, A Haroche, J Donadieu, J Requena-Caballero, L Jordan, MB Abdel-Wahab, O Allen, CE Charlotte, F Diamond, EL Egeler, RM Fischer, A Herrera, JG Henter, JI Janku, F Merad, M Picarsic, J Rodriguez-Galindo, C Rollins, BJ Tazi, A Vassallo, R Weiss, LM AF Emile, Jean-Francois Abla, Oussama Fraitag, Sylvie Horne, Annacarin Haroche, Julien Donadieu, Jean Requena-Caballero, Luis Jordan, Michael B. Abdel-Wahab, Omar Allen, Carl E. Charlotte, Frederic Diamond, Eli L. Egeler, R. Maarten Fischer, Alain Gil Herrera, Juana Henter, Jan-Inge Janku, Filip Merad, Miriam Picarsic, Jennifer Rodriguez-Galindo, Carlos Rollins, Barret J. Tazi, Abdellatif Vassallo, Robert Weiss, Lawrence M. CA Histiocyte Soc TI Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages SO BLOOD LA English DT Review ID ERDHEIM-CHESTER-DISEASE; ROSAI-DORFMAN-DISEASE; CENTRAL-NERVOUS-SYSTEM; OF-THE-LITERATURE; HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; BRAF(V600E) MUTATION; ACTIVATION SYNDROME; MASSIVE LYMPHADENOPATHY; IGG4-RELATED DISEASE; SINUS HISTIOCYTOSIS AB The histiocytoses are rare disorders characterized by the accumulation of macrophage, dendritic cell, or monocyte-derived cells in various tissues and organs of children and adults. More than 100 different subtypes have been described, with a wide range of clinical manifestations, presentations, and histologies. Since the first classification in 1987, a number of new findings regarding the cellular origins, molecular pathology, and clinical features of histiocytic disorders have been identified. We propose herein a revision of the classification of histiocytoses based on histology, phenotype, molecular alterations, and clinical and imaging characteristics. This revised classification system consists of 5 groups of diseases: (1) Langerhans-related, (2) cutaneous and mucocutaneous, and (3) malignanthistiocytoses as well as (4) Rosai-Dorfman disease and (5) hemophagocytic lymphohistiocytosis and macrophage activation syndrome. Herein, we provide guidelines and recommendations for diagnoses of these disorders. C1 [Emile, Jean-Francois; Donadieu, Jean] Paris Saclay Univ, Univ Versailles, Res Unit EA4340, Boulogne, France. [Emile, Jean-Francois] Hop Ambroise Pare, AP HP, Dept Pathol, F-92104 Boulogne, France. [Abla, Oussama; Egeler, R. Maarten] Univ Toronto, Hosp Sick Children, Dept Pediat, Div Hematol Oncol, Toronto, ON M5G 1X8, Canada. [Fraitag, Sylvie] Hop Necker Enfants Malad, Dept Pathol, Paris, France. [Horne, Annacarin] Karolinska Inst, Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Stockholm, Sweden. [Haroche, Julien] Hop La Pitie Salpetriere, AP HP, Inst E3M, Dept Internal Med, Paris, France. [Haroche, Julien] Hop La Pitie Salpetriere, AP HP, Inst E3M, French Reference Ctr Rare Autoimmune & System Dis, Paris, France. [Haroche, Julien; Charlotte, Frederic] Univ Paris 06, Paris, France. [Donadieu, Jean] Trousseau Hosp, AP HP, Pediat Hematol, Paris, France. [Requena-Caballero, Luis] Univ Autonoma Madrid, Fdn Jimenez Diaz, Madrid, Spain. [Jordan, Michael B.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA. [Jordan, Michael B.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Abdel-Wahab, Omar] Mem Sloan Kettering Canc Ctr, Leukemia Serv, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA. [Allen, Carl E.] Texas Childrens Canc Ctr, Feigin Ctr, Houston, TX USA. [Charlotte, Frederic] Hop La Pitie Salpetriere, Dept Pathol, Paris, France. [Diamond, Eli L.] Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10021 USA. [Fischer, Alain] Hop Necker Enfants Malad, AP HP, Paris, France. [Fischer, Alain] Univ Paris 05, Sorbonne Paris Cite, Inst Imagine, Paris, France. [Gil Herrera, Juana] Hosp Gen Univ, Div Clin Immunol, Madrid, Spain. [Gil Herrera, Juana] Hlth Res Inst Gregorio Maranon, Madrid, Spain. [Henter, Jan-Inge] Karolinska Inst, Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Stockholm, Sweden. [Janku, Filip] Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Phase Clin Trials Program 1, Houston, TX 77030 USA. [Merad, Miriam] Mt Sinai Sch Med, New York, NY USA. [Picarsic, Jennifer] Univ Pittsburgh, Childrens Hosp Pittsburgh, Sch Med, Dept Pathol,Med Ctr, Pittsburgh, PA USA. [Rodriguez-Galindo, Carlos] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rollins, Barret J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Rollins, Barret J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Tazi, Abdellatif] Hop St Louis, Div Pulm, Paris, France. [Vassallo, Robert] Mayo Clin, Coll Med, Div Pulm & Crit Care Med, Rochester, MN USA. [Weiss, Lawrence M.] Clarient Pathol Serv, Aliso Viejo, CA USA. RP Emile, JF (reprint author), Hop Ambroise Pare, EA4340, 9 Ave Ch de Gaulle, F-92104 Boulogne, France.; Emile, JF (reprint author), Hop Ambroise Pare, Dept Pathol, 9 Ave Ch de Gaulle, F-92104 Boulogne, France. EM jean-francois.emile@uvsq.fr FU Roche; Fondo de Investigacion Sanitaria (FIS); GSK; BioTheranostics; Genentech FX J.-F.E. received honoraria from Roche and GlaxoSmithKline (GSK). J.H. received grants from Roche. C.E.A. was an unpaid consultant to Novimmune. J.G.H. received grants from Fondo de Investigacion Sanitaria (FIS). R.V. received grants from GSK. L.M.W. received fees from BioTheranostics and Genentech. The remaining authors declare no competing financial interests. NR 98 TC 16 Z9 16 U1 5 U2 5 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 JUN 2 PY 2016 VL 127 IS 22 BP 2672 EP 2681 DI 10.1182/blood-2016-01690636 PG 10 WC Hematology SC Hematology GA DP2QS UT WOS:000378335400009 PM 26966089 ER PT J AU Richardson, PG Zimmerman, TM Hofmeister, CC Talpaz, M Chanan-Khan, AA Kaufman, JL Laubach, JP Chauhan, D Jakubowiak, AJ Reich, S Trikha, M Anderson, KC AF Richardson, Paul G. Zimmerman, Todd M. Hofmeister, Craig C. Talpaz, Moshe Chanan-Khan, Asher A. Kaufman, Jonathan L. Laubach, Jacob P. Chauhan, Dharminder Jakubowiak, Andrzej J. Reich, Steven Trikha, Mohit Anderson, Kenneth C. TI Phase 1 study of marizomib in relapsed or relapsed and refractory multiple myeloma: NPI-0052-101 Part 1 SO BLOOD LA English DT Article ID ORAL PROTEASOME INHIBITOR; VIVO SYNERGISTIC CYTOTOXICITY; BORTEZOMIB RESISTANCE; DOSE DEXAMETHASONE; TREATMENT OPTIONS; MOLECULAR-BASIS; CARFILZOMIB; THERAPY; LENALIDOMIDE; COMBINATION AB Marizomib (MRZ) is a novel, irreversible proteasome inhibitor in clinical development for the treatment of relapsed or relapsed and refractory multiple myeloma (RRMM). MRZ inhibits the 3 proteolytic activities of the 20S proteasome with specificity distinct from bortezomib and carfilzomib. Study NPI-0052-101 Part 1 enrolled relapsed or RRMM patients into an open-label, dose-escalation design to determine the maximum tolerated dose and recommended phase 2 dose (RP2D) of MRZ administered intravenously on 2 different schedules: schedule A (0.025-0.7mg/m(2) once weekly on days 1, 8, and 15 of 4-week cycles) and schedule B (0.15-0.6 mg/m(2) twice weekly on days 1, 4, 8, and 11 of 3-week cycles; concomitant dexamethasone was allowed with schedule B). Patients had received an average of 4.9 and 7.3 prior treatment regimens (schedules A and B, respectively). MRZ schedule A was administered to 32 patients, and theRP2D was established as 0.7mg/m(2) infused over 10 minutes. Schedule B was administered to 36 patients, and the RP2D was determined to be 0.5 mg/m(2) infused over 2 hours. The most common (>20% of patients) related adverse events were fatigue, headache, nausea, diarrhea, dizziness, and vomiting. Six patients achieved clinical benefit responses (defined as minimal response or better), including 5 partial responses (1 patient on schedule A and 4 on schedule B; 3 of these 4 patients received concomitant dexamethasone). MRZ was generally well tolerated, and results suggest activity in previously treated RRMM patients. Combination studies using pomalidomide and dexamethasone are now underway. The trial was registered at www.clinicaltrials.gov as #NCT00461045. C1 [Richardson, Paul G.; Laubach, Jacob P.; Chauhan, Dharminder; Anderson, Kenneth C.] Dana Farber Canc Inst, 450 Brookline Ave,Mayer 232, Boston, MA 02215 USA. [Zimmerman, Todd M.; Jakubowiak, Andrzej J.] Univ Chicago, Sch Med, Chicago, IL 60637 USA. [Hofmeister, Craig C.] Ohio State Univ, Columbus, OH 43210 USA. [Talpaz, Moshe] Univ Michigan, Ann Arbor, MI 48109 USA. [Chanan-Khan, Asher A.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Kaufman, Jonathan L.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Reich, Steven; Trikha, Mohit] Triphase Accelerator, San Diego, CA USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Mayer 232, Boston, MA 02215 USA. EM paul_richardson@dfci.harvard.edu RI Hofmeister, Craig/E-3256-2011 OI Hofmeister, Craig/0000-0003-4816-1607 FU Celgene Corporation; Merck Co.; Novartis Pharmaceuticals; Onyx Pharmaceuticals; Millenium (The Takeda Oncology Company); Triphase Accelerator Corp. FX K.C.A. is on the advisory boards of Bristol-Myers Squibb Pharmaceuticals, Celgene Corporation, Gilead Pharmaceuticals, and Millenium (The Takeda Oncology Company) and is the scientific founder of Acetylon Pharmaceutcials and OncoPep, Inc. D.C. is a consultant for Triphase Accelerator Corp. A.J.J. is a consultant for and on the advisory boards of Amgen Inc., Bristol-Myers Squibb Pharmaceuticals, Celgene Corporation, Janssen Pharmaceuticals, Karyopharm Therapeutics Inc., Millenium (The Takeda Oncology Company), SkylineDx, and Sanofi-Aventis Pharmaceuticals. J.L.K. is a member of the Data Monitoring Committee for Incyte Corporation and Pharmacyclics, is a consultant for Onyx Pharmaceuticals and Millenium (The Takeda Oncology Company), and receives research funding from Celgene Corporation, Merck & Co., Novartis Pharmaceuticals, and Onyx Pharmaceuticals. J.P.L. receives research funding from the Celgene Corporation, Millenium (The Takeda Oncology Company), Novartis Pharmaceuticals, and Onyx Pharmaceuticals and is a consultant for Novartis Pharmaceuticals. S.R. received payment from Triphase Accelerator Corp. P.G.R. serves on advisory committes of and receives research funding from Celgene Corporation and Millenium (The Takeda Oncology Company). M. Trikha is employed by and received payment from the Triphase Accelerator Corp. The remaining authors declare no competing financial interests. NR 44 TC 5 Z9 5 U1 6 U2 9 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 JUN 2 PY 2016 VL 127 IS 22 BP 2693 EP 2700 DI 10.1182/blood-2015-12686378 PG 8 WC Hematology SC Hematology GA DP2QS UT WOS:000378335400011 PM 27009059 ER PT J AU Radonovich, LJ Bessesen, MT Cummings, DA Eagan, A Gaydos, C Gibert, C Gorse, GJ Nyquist, AC Reich, NG Rodrigues-Barradas, M Savor-Price, C Shaffer, RE Simberkoff, MS Perl, TM AF Radonovich, Lewis J., Jr. Bessesen, Mary T. Cummings, Derek A. Eagan, Aaron Gaydos, Charlotte Gibert, Cynthia Gorse, Geoffrey J. Nyquist, Ann-Christine Reich, Nicholas G. Rodrigues-Barradas, Maria Savor-Price, Connie Shaffer, Ronald E. Simberkoff, Michael S. Perl, Trish M. TI The Respiratory Protection Effectiveness Clinical Trial (ResPECT): a cluster-randomized comparison of respirator and medical mask effectiveness against respiratory infections in healthcare personnel SO BMC INFECTIOUS DISEASES LA English DT Article DE Respirators; Masks; Healthcare personnel; Influenza; Respiratory infections ID NOSE-THROAT SWABS; N95 RESPIRATORS; SURGICAL MASK; NASOPHARYNGEAL ASPIRATE; FACE MASKS; NASAL SWAB; WORKERS; INFLUENZA; TRANSMISSION; PERFORMANCE AB Background: Although N95 filtering facepiece respirators and medical masks are commonly used for protection against respiratory infections in healthcare settings, more clinical evidence is needed to understand the optimal settings and exposure circumstances for healthcare personnel to use these devices. A lack of clinically germane research has led to equivocal, and occasionally conflicting, healthcare respiratory protection recommendations from public health organizations, professional societies, and experts. Methods: The Respiratory Protection Effectiveness Clinical Trial (ResPECT) is a prospective comparison of respiratory protective equipment to be conducted at multiple U.S. study sites. Healthcare personnel who work in outpatient settings will be cluster-randomized to wear N95 respirators or medical masks for protection against infections during respiratory virus season. Outcome measures will include laboratory-confirmed viral respiratory infections, acute respiratory illness, and influenza-like illness. Participant exposures to patients, coworkers, and others with symptoms and signs of respiratory infection, both within and beyond the workplace, will be recorded in daily diaries. Adherence to study protocols will be monitored by the study team. Discussion: ResPECT is designed to better understand the extent to which N95s and MMs reduce clinical illness among healthcare personnel. A fully successful study would produce clinically relevant results that help clinician-leaders make reasoned decisions about protection of healthcare personnel against occupationally acquired respiratory infections and prevention of spread within healthcare systems. C1 [Radonovich, Lewis J., Jr.; Eagan, Aaron] US Dept Vet Affairs, Natl Ctr Occupat Hlth & Infect Control, 1601 SW Archer Rd,Mailstop 151E, Gainesville, FL 32608 USA. [Bessesen, Mary T.] Vet Affairs Eastern Colorado Healthcare Syst, Denver, CO USA. [Gaydos, Charlotte; Perl, Trish M.] Johns Hopkins Sch Med, Baltimore, MD USA. [Gibert, Cynthia] Vet Affairs Med Ctr, 50 Irving St NW, Washington, DC 20422 USA. [Gibert, Cynthia] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. [Gorse, Geoffrey J.] Vet Affairs St Louis Healthcare Syst, St Louis, MO USA. [Gorse, Geoffrey J.] St Louis Univ, Sch Med, St Louis, MO 63103 USA. [Nyquist, Ann-Christine] Childrens Hosp Colorado, Aurora, CO USA. [Reich, Nicholas G.] Univ Massachusetts, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. [Rodrigues-Barradas, Maria] Michael E DeBakey VAMC, Houston, TX USA. [Rodrigues-Barradas, Maria] Baylor Coll Med, Houston, TX 77030 USA. [Savor-Price, Connie] Denver Hlth, Denver, CO USA. [Shaffer, Ronald E.] NIOSH, Natl Personal Protect Technol Lab, Pittsburgh, PA USA. [Simberkoff, Michael S.] Vet Affairs New York Harbor Healthcare Syst, New York, NY USA. [Bessesen, Mary T.; Nyquist, Ann-Christine; Savor-Price, Connie] Univ Colorado, Sch Med, Denver, CO 80202 USA. [Cummings, Derek A.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Cummings, Derek A.] Univ Florida, Gainesville, FL USA. RP Radonovich, LJ (reprint author), US Dept Vet Affairs, Natl Ctr Occupat Hlth & Infect Control, 1601 SW Archer Rd,Mailstop 151E, Gainesville, FL 32608 USA. EM lewis.radonovich@va.gov FU U.S. Department of Veterans Affairs (Veterans Health Administration); U.S. Department of Health and Human Services (Centers for Disease Control and Prevention); U.S. Department of Health and Human Services (National Institute for Occupational Safety and Health); U.S. Department of Health and Human Services (Biomedical Advanced Research and Development Authority) FX We wish to thank the members of the ResPECT Team (complete list to be provided prior to publication). ResPECT is jointly funded by the U.S. Department of Veterans Affairs (Veterans Health Administration) and the U.S. Department of Health and Human Services (Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, and the Biomedical Advanced Research and Development Authority). NR 49 TC 0 Z9 0 U1 3 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD JUN 2 PY 2016 VL 16 AR 243 DI 10.1186/s12879-016-1494-2 PG 10 WC Infectious Diseases SC Infectious Diseases GA DO7EA UT WOS:000377944000001 PM 27255755 ER PT J AU Green, RC Goddard, KAB Jarvik, GP Amendola, LM Appelbaum, PS Berg, JS Bernhardt, BA Biesecker, LG Biswas, S Blout, CL Bowling, KM Brothers, KB Burke, W Caga-anan, CF Chinnaiyan, AM Chung, WK Clayton, EW Cooper, GM East, K Evans, JP Fullerton, SM Garraway, LA Garrett, JR Gray, SW Henderson, GE Hindorff, LA Holm, IA Lewis, MH Hutter, CM Janne, PA Joffe, S Kaufman, D Knoppers, BM Koenig, BA Krantz, ID Manolio, TA McCullough, L McEwen, J McGuire, A Muzny, D Myers, RM Nickerson, DA Ou, J Parsons, DW Petersen, GM Plon, SE Rehm, HL Roberts, JS Robinson, D Salama, JS Scollon, S Sharp, RR Shirts, B Spinner, NB Tabor, HK Tarczy-Hornoch, P Veenstra, DL Wagle, N Weck, K Wilfond, BS Wilhelmsen, K Wolf, SM Wynn, J Yu, JH AF Green, Robert C. Goddard, Katrina A. B. Jarvik, Gail P. Amendola, Laura M. Appelbaum, Paul S. Berg, Jonathan S. Bernhardt, Barbara A. Biesecker, Leslie G. Biswas, Sawona Blout, Carrie L. Bowling, Kevin M. Brothers, Kyle B. Burke, Wylie Caga-anan, Charlisse F. Chinnaiyan, Arul M. Chung, Wendy K. Clayton, Ellen W. Cooper, Gregory M. East, Kelly Evans, James P. Fullerton, Stephanie M. Garraway, Levi A. Garrett, Jeremy R. Gray, Stacy W. Henderson, Gail E. Hindorff, Lucia A. Holm, Ingrid A. Lewis, Michelle Huckaby Hutter, Carolyn M. Janne, Pasi A. Joffe, Steven Kaufman, David Knoppers, Bartha M. Koenig, Barbara A. Krantz, Ian D. Manolio, Teri A. McCullough, Laurence McEwen, Jean McGuire, Amy Muzny, Donna Myers, Richard M. Nickerson, Deborah A. Ou, Jeffrey Parsons, Donald W. Petersen, Gloria M. Plon, Sharon E. Rehm, Heidi L. Roberts, J. Scott Robinson, Dan Salama, Joseph S. Scollon, Sarah Sharp, Richard R. Shirts, Brian Spinner, Nancy B. Tabor, Holly K. Tarczy-Hornoch, Peter Veenstra, David L. Wagle, Nikhil Weck, Karen Wilfond, Benjamin S. Wilhelmsen, Kirk Wolf, Susan M. Wynn, Julia Yu, Joon-Ho CA CSER Consortium TI Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID OBTAINING INFORMED-CONSENT; GENETIC RESEARCH FINDINGS; ELECTRONIC HEALTH RECORD; INCIDENTAL-FINDINGS; WHOLE-EXOME; MEDSEQ PROJECT; RESEARCH PARTICIPANTS; ACMG RECOMMENDATIONS; BEHAVIORAL ECONOMICS; PERCEIVED UTILITY AB Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstreamcosts of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine. C1 [Green, Robert C.; Blout, Carrie L.] Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA. [Green, Robert C.; Garraway, Levi A.; Rehm, Heidi L.; Wagle, Nikhil] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Green, Robert C.; Gray, Stacy W.; Holm, Ingrid A.; Janne, Pasi A.; Rehm, Heidi L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Green, Robert C.; Rehm, Heidi L.] Partners Personalized Med, Boston, MA 02139 USA. [Goddard, Katrina A. B.] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR 97227 USA. [Jarvik, Gail P.; Nickerson, Deborah A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Jarvik, Gail P.; Amendola, Laura M.; Burke, Wylie; Ou, Jeffrey; Salama, Joseph S.; Tarczy-Hornoch, Peter] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Jarvik, Gail P.; Amendola, Laura M.; Burke, Wylie; Ou, Jeffrey; Salama, Joseph S.] Univ Washington, Clin Sequencing Exploratory Res Coordinating Ctr, Seattle, WA 98195 USA. [Appelbaum, Paul S.] Columbia Univ, Med Ctr, Dept Psychiat, New York, NY 10032 USA. [Appelbaum, Paul S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Berg, Jonathan S.; Evans, James P.; Weck, Karen; Wilhelmsen, Kirk] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Bernhardt, Barbara A.; Biswas, Sawona; Krantz, Ian D.; Spinner, Nancy B.] Univ Penn, Perelman Sch Med, Dept Med, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA. [Biesecker, Leslie G.] NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA. [Biswas, Sawona; Krantz, Ian D.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Bowling, Kevin M.; Cooper, Gregory M.; East, Kelly; Myers, Richard M.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA. [Brothers, Kyle B.] Univ Louisville, Dept Pediat, Louisville, KY 40202 USA. [Burke, Wylie; Fullerton, Stephanie M.] Univ Washington, Dept Med, Dept Bioeth & Humanities, Seattle, WA 98195 USA. [Caga-anan, Charlisse F.] NCI, NIH, Bethesda, MD 20892 USA. [Chinnaiyan, Arul M.; Robinson, Dan] Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA. [Chinnaiyan, Arul M.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Chinnaiyan, Arul M.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Chinnaiyan, Arul M.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. [Chinnaiyan, Arul M.] Howard Hughes Med Inst, Ann Arbor, MI 48109 USA. [Chung, Wendy K.; Wynn, Julia] Columbia Univ, Dept Pediat, New York, NY 10029 USA. [Chung, Wendy K.] Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA. [Clayton, Ellen W.] Vanderbilt Univ, Ctr Biomed Eth & Soc, Nashville, TN 37203 USA. [Garraway, Levi A.; Wagle, Nikhil] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Garraway, Levi A.; Wagle, Nikhil] Dana Farber Canc Inst, Ctr Canc Precis Med, Boston, MA 02115 USA. [Garraway, Levi A.; Wagle, Nikhil] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Garrett, Jeremy R.] Childrens Mercy Hosp, Childrens Mercy Bioeth Ctr, Kansas City, MO 64108 USA. [Garrett, Jeremy R.] Univ Missouri, Dept Pediat, Kansas City, MO 64110 USA. [Garrett, Jeremy R.] Univ Missouri, Dept Philosophy, Kansas City, MO 64110 USA. [Gray, Stacy W.; Janne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Henderson, Gail E.] Univ N Carolina, Sch Med, Dept Social Med, Chapel Hill, NC 27599 USA. [Hindorff, Lucia A.; Hutter, Carolyn M.; Manolio, Teri A.] NHGRI, Div Genom Med, NIH, Bethesda, MD 20892 USA. [Holm, Ingrid A.] Boston Childrens Hosp, Div Genet & Genom, Boston, MA 02115 USA. [Holm, Ingrid A.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Lewis, Michelle Huckaby] Johns Hopkins, Berman Inst Bioeth, Baltimore, MD 21205 USA. [Joffe, Steven; McGuire, Amy] Univ Penn, Sch Med, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Kaufman, David; McEwen, Jean] NHGRI, Div Genom & Soc, NIH, Bethesda, MD 20892 USA. [Knoppers, Bartha M.] McGill Univ, Dept Human Genet, Fac Med, Ctr Genom & Policy, Montreal, PQ H3A 1B1, Canada. [Koenig, Barbara A.] Univ Calif San Francisco, Inst Hlth & Aging, San Francisco, CA 94118 USA. [McCullough, Laurence; McGuire, Amy] Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA. [Muzny, Donna] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Parsons, Donald W.; Plon, Sharon E.] Baylor Coll Med, Houston, TX 77030 USA. [Parsons, Donald W.; Plon, Sharon E.] Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Petersen, Gloria M.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Rehm, Heidi L.] Partners HealthCare, Mol Med Lab, Cambridge, MA 02139 USA. [Roberts, J. Scott] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. [Scollon, Sarah] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Sharp, Richard R.] Mayo Clin, Coll Med, Biomed Eth Res Program, Rochester, MN 55905 USA. [Shirts, Brian] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Spinner, Nancy B.] Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Tabor, Holly K.; Wilfond, Benjamin S.; Yu, Joon-Ho] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Tabor, Holly K.; Wilfond, Benjamin S.] Univ Washington, Seattle Childrens Res Inst, Seattle, WA 98195 USA. [Tarczy-Hornoch, Peter] Univ Washington, Seattle, WA 98105 USA. [Veenstra, David L.] Univ Washington, Dept Pharm, Seattle, WA 98195 USA. [Weck, Karen] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. [Wolf, Susan M.] Univ Minnesota, Sch Med, Sch Law, Minneapolis, MN 55455 USA. [Wolf, Susan M.] Univ Minnesota, Consortium Law & Values Hlth Environm & Life Sci, Minneapolis, MN 55455 USA. RP Green, RC (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA.; Green, RC (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.; Green, RC (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.; Green, RC (reprint author), Partners Personalized Med, Boston, MA 02139 USA. EM rcgreen@genetics.med.harvard.edu OI Tarczy-Hornoch, Peter/0000-0003-1047-179X; Lebo, Matthew/0000-0002-9733-5207; Seifert, Bryce/0000-0001-7970-3611 FU NHGRI; [U01HG0006546]; [U01HG006485]; [U01HG006500]; [U01HG006492]; [UM1HG007301]; [UM1HG007292]; [UM1HG006508]; [U01HG006487]; [U01HG006507]; [U01HG007307]; [U01HG006379]; [U41HG006834]; [U54HG003273]; [R21HG006596]; [P20HG007243]; [P50HG007257]; [R01HG006600]; [R01HG004500]; [R01CA154517]; [R01HG006618]; [R21HG006594]; [R01HG006615]; [R21HG006612]; [5R21HG006613]; [R01HG007063]; [HG008685]; [UL1TR000423]; [UA01AG047109]; [K99HG007076] FX The authors thank Julia Fekecs of the National Human Genome Research Institute (NHGRI) for her technical assistance with Figure 1. The authors would like to thank all of the Clinical Sequencing Exploratory Research (CSER) participants for their involvement in this research. The authors also thank the members of their CSER advisory panel: Katrina Armstrong, MD; Rex L. Chisholm, PhD; Mildred K. Cho, PhD; Chanita H. Halbert, PhD; Elaine Lyon, PhD; Kenneth Offit, MD; Dan Roden, MD; Pamela Sankar, PhD; and Alan Williamson, PhD. The research described in this report was funded by grants U01HG0006546, U01HG006485, U01HG006500, U01HG006492, UM1HG007301, UM1HG007292, UM1HG006508, U01HG006487, U01HG006507, U01HG007307, U01HG006379, U41HG006834, U54HG003273, R21HG006596, P20HG007243, R01HG006600, P50HG007257, R01HG006600, R01HG004500, R01CA154517, R01HG006618, R21HG006594, R01HG006615, R21HG006612, 5R21HG006613, R01HG007063, HG008685, UL1TR000423, UA01AG047109, and K99HG007076. ClinSeq is supported by the NHGRI Intramural Research Program. C.F.C.-A., L.A.H., C.M.H., D.K., T.A.M., and J.M. are members of the NIH CSER staff team, responsible for management of the CSER program. NR 109 TC 12 Z9 12 U1 4 U2 10 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 JUN 2 PY 2016 VL 98 IS 6 BP 1051 EP 1066 DI 10.1016/j.ajhg.2016.04.011 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA DN7US UT WOS:000377286000001 PM 27181682 ER PT J AU Amendola, LM Jarvik, GP Leo, MC McLaughlin, HM Akkari, Y Amaral, MD Berg, JS Biswas, S Bowling, KM Conlin, LK Cooper, GM Dorschner, MO Dulik, MC Ghazani, AA Ghosh, R Green, RC Hart, R Horton, C Johnston, JJ Lebo, MS Milosavljevic, A Ou, J Pak, CM Patel, RY Punj, S Richards, CS Salama, J Strande, NT Yang, YP Plon, SE Biesecker, LG Rehm, HL AF Amendola, Laura M. Jarvik, Gail P. Leo, Michael C. McLaughlin, Heather M. Akkari, Yassmine Amaral, Michelle D. Berg, Jonathan S. Biswas, Sawona Bowling, Kevin M. Conlin, Laura K. Cooper, Greg M. Dorschner, Michael O. Dulik, Matthew C. Ghazani, Arezou A. Ghosh, Rajarshi Green, Robert C. Hart, Ragan Horton, Carrie Johnston, Jennifer J. Lebo, Matthew S. Milosavljevic, Aleksandar Ou, Jeffrey Pak, Christine M. Patel, Ronak Y. Punj, Sumit Richards, Carolyn Sue Salama, Joseph Strande, Natasha T. Yang, Yaping Plon, Sharon E. Biesecker, Leslie G. Rehm, Heidi L. TI Performance of ACMG-AMP Variant-Interpretation Guidelines among Nine Laboratories in the Clinical Sequencing Exploratory Research Consortium SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SPASTIC PARAPLEGIA; GENE; MUTATION; RECOMMENDATIONS; PHENOTYPE; STANDARDS; TESTS; SPG7 AB Evaluating the pathogenicity of a variant is challenging given the plethora of types of genetic evidence that laboratories consider. Deciding how to weigh each type of evidence is difficult, and standards have been needed. In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published guidelines for the assessment of variants in genes associated with Mendelian diseases. Nine molecular diagnostic laboratories involved in the Clinical Sequencing Exploratory Research (CSER) consortium piloted these guidelines on 99 variants spanning all categories (pathogenic, likely pathogenic, uncertain significance, likely benign, and benign). Nine variants were distributed to all laboratories, and the remaining 90 were evaluated by three laboratories. The laboratories classified each variant by using both the laboratory's own method and the ACMG-AMP criteria. The agreement between the two methods used within laboratories was high (K-alpha = 0.91) with 79% concordance. However, there was only 34% concordance for either classification system across laboratories. After consensus discussions and detailed review of the ACMG=AMP criteria, concordance increased to 71%. Causes of initial discordance in ACMG-AMP classifications were identified, and recommendations on clarification and increased specification of the ACMG-AMP criteria were made. In summary, although an initial pilot of the ACMG-AMP guidelines did not lead to increased concordance in variant interpretation, comparing variant interpretations to identify differences and having a common framework to facilitate resolution of those differences were beneficial for improving agreement, allowing iterative movement toward increased reporting consistency for variants in genes associated with monogenic disease. C1 [Amendola, Laura M.; Jarvik, Gail P.; Hart, Ragan; Ou, Jeffrey; Salama, Joseph] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Leo, Michael C.] Kaiser Permanente, Ctr Hlth Res, Portland, OR 97227 USA. [McLaughlin, Heather M.; Green, Robert C.; Lebo, Matthew S.; Rehm, Heidi L.] Partners HealthCare Personalized Med, Mol Med Lab, Cambridge, MA 02139 USA. [Akkari, Yassmine; Pak, Christine M.; Punj, Sumit; Richards, Carolyn Sue] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA. [Amaral, Michelle D.; Bowling, Kevin M.; Cooper, Greg M.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA. [Berg, Jonathan S.; Strande, Natasha T.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Biswas, Sawona; Conlin, Laura K.] Childrens Hosp Philadelphia, Dept Pediat, Div Human Genet, Philadelphia, PA 19104 USA. [Dorschner, Michael O.] Univ Washington, Dept Pathol, Ctr Precis Diagnost, Seattle, WA 98195 USA. [Dulik, Matthew C.] Childrens Hosp Philadelphia, Dept Pathol & LaboratoryMedicine, Philadelphia, PA 19104 USA. [Ghazani, Arezou A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Ghosh, Rajarshi; Milosavljevic, Aleksandar; Patel, Ronak Y.; Yang, Yaping; Plon, Sharon E.] Baylor Coll Med, Houston, TX 77030 USA. [Green, Robert C.; Lebo, Matthew S.; Rehm, Heidi L.] Brigham & Womens Hosp, Cambridge, MA 02115 USA. [Green, Robert C.; Lebo, Matthew S.; Rehm, Heidi L.] Harvard Univ, Sch Med, Cambridge, MA 02115 USA. [Horton, Carrie] Ambry Genet, Clin Diagnost, Aliso Viejo, CA 92656 USA. [Johnston, Jennifer J.; Biesecker, Leslie G.] NHGRI, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Green, Robert C.; Rehm, Heidi L.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. RP Jarvik, GP (reprint author), Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA.; Rehm, HL (reprint author), Partners HealthCare Personalized Med, Mol Med Lab, Cambridge, MA 02139 USA.; Rehm, HL (reprint author), Brigham & Womens Hosp, Cambridge, MA 02115 USA.; Rehm, HL (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02115 USA.; Rehm, HL (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM pair@u.washington.edu; hrehm@partners.org OI Strande, Natasha/0000-0001-5148-9772; Lebo, Matthew/0000-0002-9733-5207 FU National Human Genome Research Institute (NHGRI); National Cancer Institute [UO1HG0006546, U01HG006485, U01HG006500, U01HG006492, UM1HG007301, UM1HG007292, UM1HG006508, U01HG006487, U01HG006507, U01HG007307, U41HG006834]; NIH NHGRI; The National Cancer Institute [R21HG006596, P50HG007257, R01HG006600, R01HG004500, R01CA154517, R01HG006618, R21HG006594-01, R01HG006615-01, R21HG006612, 5R21HG006613-02] FX This work was funded by the National Human Genome Research Institute (NHGRI) and National Cancer Institute (UO1HG0006546, U01HG006485, U01HG006500, U01HG006492, UM1HG007301, UM1HG007292, UM1HG006508, U01HG006487, U01HG006507, U01HG007307, U41HG006834, R21HG006596, R01HG006600, P50HG007257, R01HG006600, R01HG004500, R01CA154517, R01HG006618, R21HG006594-01, R01HG006615-01, R21HG006612, and 5R21HG006613-02) and additional support from the participating laboratories. This research was supported in part by the Intramural Research Program of the NIH NHGRI. We thank the following individuals for contributing to variant assessment at the sites: Hana Zouk, PhD; Steven M. Harrison, PhD; Jillian G. Buchan, PhD; Jessica Booker, PhD; Jim Evans, MD, PhD, Kate Foreman, MS; Gloria Haskell, PhD; Kristy Lee, MS; Julianne O'Daniel, MS; Bradford Powell, MD, PhD; Bryce Seifert, PhD; and Karen Weck, MD. NR 26 TC 26 Z9 26 U1 0 U2 2 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 JUN 2 PY 2016 VL 98 IS 6 BP 1067 EP 1076 DI 10.1016/j.ajhg.2016.03.024 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA DN7US UT WOS:000377286000002 PM 27181684 ER PT J AU Chalermrujinanant, C Michowski, W Sittithumcharee, G Esashi, F Jirawatnotai, S AF Chalermrujinanant, C. Michowski, W. Sittithumcharee, G. Esashi, F. Jirawatnotai, S. TI Cyclin D1 promotes BRCA2-Rad51 interaction by restricting cyclin A/B-dependent BRCA2 phosphorylation SO ONCOGENE LA English DT Article ID STRAND BREAK REPAIR; DNA-END RESECTION; HOMOLOGY-DIRECTED REPAIR; MANTLE CELL LYMPHOMA; GENOMIC STABILITY; DAMAGE REPAIR; CANCER; PROTEIN; GENE; RECOMBINATION AB BRCA2 has an important role in the maintenance of genome stability by interacting with RAD51 recombinase through its C-terminal domain. This interaction is abrogated by cyclin A-CDK2-mediated phosphorylation of BRCA2 at serine 3291 (Ser3291). Recently, we showed that cyclin D1 facilitates RAD51 recruitment to BRCA2-containing DNA repair foci, and that downregulation of cyclin D1 leads to inefficient homologous-mediated DNA repair. Here, we demonstrate that cyclin D1, via amino acids 20-90, interacts with the C-terminal domain of BRCA2, and that this interaction is increased in response to DNA damage. Interestingly, CDK4-cyclin D1 does not phosphorylate Ser3291. Instead, cyclin D1 bars cyclin A from the C-terminus of BRCA2, prevents cyclin A-CDK2-dependent Ser3291 phosphorylation and facilitates RAD51 binding to the C-terminal domain of BRCA2. These findings indicate that the interplay between cyclin D1 and other cyclins such as cyclin A regulates DNA integrity through RAD51 interaction with the BRCA2 C-terminal domain. C1 [Chalermrujinanant, C.; Sittithumcharee, G.; Jirawatnotai, S.] Mahidol Univ, Siriraj Hosp, Fac Med, Lab Syst Pharmacol,Dept Pharmacol, 2 Prannok Rd,12th Floor Srisawarin Bldg, Bangkok 10700, Thailand. [Michowski, W.; Jirawatnotai, S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Esashi, F.] Univ Oxford, Sir William Dunn Sch Pathol, S Parks Rd, Oxford OX1 3RE, England. [Jirawatnotai, S.] Mahidol Univ, Inst Mol Biosci, Bangkok 10700, Thailand. RP Jirawatnotai, S (reprint author), Mahidol Univ, Siriraj Hosp, Fac Med, Lab Syst Pharmacol,Dept Pharmacol, 2 Prannok Rd,12th Floor Srisawarin Bldg, Bangkok 10700, Thailand. EM siwanon.jir@mahidol.ac.th OI Esashi, Fumiko/0000-0003-0902-2364 FU Thailand Research Fund [RSA5580018]; Siriraj Research Fund, Faculty of Medicine Siriraj Hospital, Mahidol University; Advanced Research on Pharmacology Fund, Siriraj Foundation [D003421]; Chalermphrakiat Grant, Faculty of Medicine Siriraj Hospital, Mahidol University FX We thank Dr Piotr Sicinski, Dana-Farber Cancer Institute, in whose laboratory this work was initiated. This study was supported by Thailand Research Fund RSA5580018, Siriraj Research Fund, Faculty of Medicine Siriraj Hospital, Mahidol University, and the Advanced Research on Pharmacology Fund, Siriraj Foundation D003421. SJ was supported by the Chalermphrakiat Grant, Faculty of Medicine Siriraj Hospital, Mahidol University. NR 60 TC 2 Z9 2 U1 4 U2 8 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 JUN 2 PY 2016 VL 35 IS 22 BP 2815 EP 2823 DI 10.1038/onc.2015.354 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA DO0MT UT WOS:000377473700001 PM 26387543 ER PT J AU Sosulski, A Horn, H Zhang, LH Coletti, C Vathipadiekal, V Castro, CM Birrer, MJ Nagano, O Saya, H Lage, K Donahoe, PK Pepin, D AF Sosulski, Amanda Horn, Heiko Zhang, Lihua Coletti, Caroline Vathipadiekal, Vinod Castro, Cesar M. Birrer, Michael J. Nagano, Osamu Saya, Hideyuki Lage, Kasper Donahoe, Patricia K. Pepin, David TI CD44 Splice Variant v8-10 as a Marker of Serous Ovarian Cancer Prognosis SO PLOS ONE LA English DT Article ID MULLERIAN-INHIBITING SUBSTANCE; TUMOR-CELL MIGRATION; FAVORABLE PROGNOSIS; ADHESION MOLECULE; E-CADHERIN; EXPRESSION; CLEAVAGE; SPECTRUM; RESISTANCE; MECHANISM AB CD44 is a transmembrane hyaluronic acid receptor gene that encodes over 100 different tissue-specific protein isoforms. The most ubiquitous, CD44 standard, has been used as a cancer stem cell marker in ovarian and other cancers. Expression of the epithelial CD44 variant containing exons v8-10 (CD44v8-10) has been associated with more chemoresistant and metastatic tumors in gastrointestinal and breast cancers, but its role in ovarian cancer is unknown; we therefore investigated its use as a prognostic marker in this disease. The gene expression profiles of 254 tumor samples from The Cancer Genome Atlas RNAseqV2 were analyzed for the presence of CD44 isoforms. A trend for longer survival was observed in patients with high expression of CD44 isoforms that include exons v8-10. Immunohistochemical (IHC) analysis of tumors for presence of CD44v8-10 was performed on an independent cohort of 210 patients with high-grade serous ovarian cancer using a tumor tissue microarray. Patient stratification based on software analysis of staining revealed a statistically significant increase in survival in patients with the highest levels of transmembrane protein expression (top 10 or 20%) compared to those with the lowest expression (bottom 10 and 20%) (p = 0.0181, p = 0.0262 respectively). Expression of CD44v8-10 in primary ovarian cancer cell lines was correlated with a predominantly epithelial phenotype characterized by high expression of epithelial markers and low expression of mesenchymal markers by qPCR, Western blot, and IHC. Conversely, detection of proteolytically cleaved and soluble extracellular domain of CD44v8-10 in patient ascites samples was correlated with significantly worse prognosis (p<0.05). Therefore, presence of transmembrane CD44v8-10 on the surface of primary tumor cells may be a marker of a highly epithelial tumor with better prognosis while enzymatic cleavage of CD44v8-10, as detected by presence of the soluble extracellular domain in ascites fluid, may be indicative of a more metastatic disease and worse prognosis. C1 [Sosulski, Amanda; Horn, Heiko; Zhang, Lihua; Coletti, Caroline; Lage, Kasper; Donahoe, Patricia K.; Pepin, David] Massachusetts Gen Hosp, Dept Surg, Pediat Surg Res Labs, Boston, MA 02114 USA. [Sosulski, Amanda; Zhang, Lihua; Coletti, Caroline; Donahoe, Patricia K.; Pepin, David] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Horn, Heiko; Lage, Kasper; Donahoe, Patricia K.; Pepin, David] Broad Inst, Cambridge, MA USA. [Vathipadiekal, Vinod; Castro, Cesar M.; Birrer, Michael J.] Massachusetts Gen Hosp, Dept Med, Gynecol Oncol, Boston, MA 02114 USA. [Vathipadiekal, Vinod; Castro, Cesar M.; Birrer, Michael J.] Harvard Univ, Sch Med, Boston, MA USA. [Nagano, Osamu; Saya, Hideyuki] Keio Univ, Sch Med, Inst Adv Med Res, Div Gene Regulat,Shinjuku Ku, 35 Shinanomachi, Tokyo, Japan. [Nagano, Osamu; Saya, Hideyuki] Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol CREST, Tokyo, Japan. RP Pepin, D (reprint author), Massachusetts Gen Hosp, Dept Surg, Pediat Surg Res Labs, Boston, MA 02114 USA.; Pepin, D (reprint author), Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.; Pepin, D (reprint author), Broad Inst, Cambridge, MA USA. EM dpepin@mgh.harvard.edu RI Nagano, Osamu/J-5874-2013; OI Nagano, Osamu/0000-0002-7630-142X; Horn, Heiko/0000-0003-4898-0557 NR 33 TC 3 Z9 3 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 2 PY 2016 VL 11 IS 6 AR e0156595 DI 10.1371/journal.pone.0156595 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DN6XB UT WOS:000377218700040 PM 27253518 ER PT J AU Storsve, AB Fjell, AM Yendiki, A Walhovd, KB AF Storsve, Andreas B. Fjell, Anders M. Yendiki, Anastasia Walhovd, Kristine B. TI Longitudinal Changes in White Matter Tract Integrity across the Adult Lifespan and Its Relation to Cortical Thinning SO PLOS ONE LA English DT Article ID AGE-RELATED DIFFERENCES; HUMAN CEREBRAL-CORTEX; SURFACE-BASED ANALYSIS; HUMAN BRAIN; OLDER-ADULTS; ALZHEIMERS-DISEASE; COORDINATE SYSTEM; MRI DATA; IN-VIVO; THICKNESS AB A causal link between decreases in white matter (WM) integrity and cortical degeneration is assumed, but there is scarce knowledge on the relationship between these changes across the adult human lifespan. We investigated changes in thickness throughout the cortical mantle and WM tract integrity derived from T1 and diffusion weighted magnetic resonance imaging (MRI) scans in 201 healthy adults aged 23-87 years over a mean interval of 3.6 years. Fractional anisotropy (FA), mean (MD), radial (RD) and axial (AD) diffusivity changes were calculated for forceps minor and major and eight major white matter tracts in each hemisphere by use of a novel automated longitudinal tractography constrained by underlying anatomy (TRACULA) approach. We hypothesized that increasing MD and decreasing FA across tracts would relate to cortical thinning, with some anatomical specificity. WM integrity decreased across tracts non-uniformly, with mean annual percentage decreases ranging from 0.20 in the Inferior Longitudinal Fasciculus to 0.65 in the Superior Longitudinal Fasciculus. For most tracts, greater MD increases and FA decreases related to more cortical thinning, in areas in part overlapping with but also outside the projected tract endings. The findings indicate a combination of global and tract-specific relationships between WM integrity and cortical thinning. C1 [Storsve, Andreas B.; Fjell, Anders M.; Walhovd, Kristine B.] Univ Oslo, Dept Psychol, Res Grp Lifespan Changes Brain & Cognit, N-0373 Oslo, Norway. [Fjell, Anders M.; Walhovd, Kristine B.] Oslo Univ Hosp, Unit Neuropsychol, Dept Phys Med & Rehabil, N-0424 Oslo, Norway. [Yendiki, Anastasia] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Yendiki, Anastasia] Harvard Univ, Sch Med, Boston, MA USA. RP Storsve, AB (reprint author), Univ Oslo, Dept Psychol, Res Grp Lifespan Changes Brain & Cognit, N-0373 Oslo, Norway. EM a.b.storsve@psykologi.uio.no FU Department of Psychology, University of Oslo; Norwegian Research Council; European Research Council [313440, 283634]; US-Norway Fulbright Foundation; National Institute for Biomedical Imaging and Bioengineering [R00-EB008129, R01-EB006758]; National Institutes of Health Blueprint for Neuroscience Research [5U01-MH093765]; National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health [P41EB015896]; NIH Shared Instrumentation Grants [S10RR023401, S10RR019307, S10RR019254, S10RR023043] FX This work was supported by the Department of Psychology, University of Oslo (A.B.S., K.B.W.), the Norwegian Research Council (to K.B.W., A.M.F.), the European Research Council's Starting Grant scheme (Grant 313440 to K.B.W. and Grant 283634 to A.M.F.), the US-Norway Fulbright Foundation (to A.B.S.), the National Institute for Biomedical Imaging and Bioengineering (R00-EB008129, R01-EB006758) (to A.Y.) and the National Institutes of Health Blueprint for Neuroscience Research (5U01-MH093765) (to A.Y.), part of the multi-institutional Human Connectome Project. Additional resources were provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health (to A.Y.). This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grants S10RR023401, S10RR019307, S10RR019254, S10RR023043. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 89 TC 1 Z9 1 U1 1 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 JUN 2 PY 2016 VL 11 IS 6 AR e0156770 DI 10.1371/journal.pone.0156770 PG 21 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DN6XB UT WOS:000377218700057 PM 27253393 ER PT J AU Sutherland, MT Riedel, MC Flannery, JS Yanes, JA Fox, PT Stein, EA Laird, AR AF Sutherland, Matthew T. Riedel, Michael C. Flannery, Jessica S. Yanes, Julio A. Fox, Peter T. Stein, Elliot A. Laird, Angela R. TI Chronic cigarette smoking is linked with structural alterations in brain regions showing acute nicotinic drug-induced functional modulations SO BEHAVIORAL AND BRAIN FUNCTIONS LA English DT Article DE Cigarettes; Nicotine; Addiction; Gray matter; Morphometry; Insula; Mediodorsal thalamus; Ventromedial prefrontal cortex; Cerebellum ID GRAY-MATTER VOLUME; INTRINSIC CONNECTIVITY NETWORKS; VOXEL-BASED MORPHOMETRY; YOUNG-ADULT SMOKERS; NEUROIMAGING DATA; DECISION-MAKING; METAANALYTIC CONNECTIVITY; ACETYLCHOLINE-RECEPTORS; COGNITIVE-PROCESSES; CORTICAL THICKNESS AB Background: Whereas acute nicotine administration alters brain function which may, in turn, contribute to enhanced attention and performance, chronic cigarette smoking is linked with regional brain atrophy and poorer cognition. However, results from structural magnetic resonance imaging (MRI) studies comparing smokers versus nonsmokers have been inconsistent and measures of gray matter possess limited ability to inform functional relations or behavioral implications. The purpose of this study was to address these interpretational challenges through metaanalytic techniques in the service of clarifying the impact of chronic smoking on gray matter integrity and more fully contextualizing such structural alterations. Methods: We first conducted a coordinate-based meta-analysis of structural MRI studies to identify consistent structural alterations associated with chronic smoking. Subsequently, we conducted two additional meta-analytic assessments to enhance insight into potential functional and behavioral relations. Specifically, we performed a multimodal meta-analytic assessment to test the structural-functional hypothesis that smoking-related structural alterations overlapped those same regions showing acute nicotinic drug-induced functional modulations. Finally, we employed database driven tools to identify pairs of structurally impacted regions that were also functionally related via meta-analytic connectivity modeling, and then delineated behavioral phenomena associated with such functional interactions via behavioral decoding. Results: Across studies, smoking was associated with convergent structural decreases in the left insula, right cerebellum, parahippocampus, multiple prefrontal cortex (PFC) regions, and the thalamus. Indicating a structural-functional relation, we observed that smoking-related gray matter decreases overlapped with the acute functional effects of nicotinic agonist administration in the left insula, ventromedial PFC, and mediodorsal thalamus. Suggesting structural-behavioral implications, we observed that the left insula's task-based, functional interactions with multiple other structurally impacted regions were linked with pain perception, the right cerebellum's interactions with other regions were associated with overt body movements, interactions between the parahippocampus and thalamus were linked with memory processes, and interactions between medial PFC regions were associated with face processing. Conclusions: Collectively, these findings emphasize brain regions (e.g., ventromedial PFC, insula, thalamus) critically linked with cigarette smoking, suggest neuroimaging paradigms warranting additional consideration among smokers (e.g., pain processing), and highlight regions in need of further elucidation in addiction (e.g., cerebellum). C1 [Sutherland, Matthew T.; Riedel, Michael C.; Flannery, Jessica S.] Florida Int Univ, Dept Psychol, AHC 4,RM 312,11200 SW 8th St, Miami, FL 33199 USA. [Riedel, Michael C.; Laird, Angela R.] Florida Int Univ, Dept Phys, Miami, FL 33199 USA. [Yanes, Julio A.] Auburn Univ, Dept Psychol, Auburn, AL 36849 USA. [Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Fox, Peter T.] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China. [Stein, Elliot A.] NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH DHHS, Baltimore, MD USA. RP Sutherland, MT (reprint author), Florida Int Univ, Dept Psychol, AHC 4,RM 312,11200 SW 8th St, Miami, FL 33199 USA. EM masuther@fiu.edu OI Sutherland, Matthew/0000-0002-6091-4037 FU National Institute on Drug Abuse of the NIH [K01-DA037819]; National Institute of Mental Health of the NIH [R01-MH074457, R56-MH097870]; Intramural Research Program of the National Institute on Drug Abuse FX This work was supported by the National Institute on Drug Abuse (K01-DA037819, MTS) and the National Institute of Mental Health (R01-MH074457 and R56-MH097870, ARL and PTF) of the NIH. EAS is supported by the Intramural Research Program of the National Institute on Drug Abuse. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 112 TC 1 Z9 1 U1 3 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-9081 J9 BEHAV BRAIN FUNCT JI Behav. Brain Funct. PD JUN 2 PY 2016 VL 12 AR 16 DI 10.1186/s12993-016-0100-5 PG 15 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA DN4TV UT WOS:000377061000001 PM 27251183 ER PT J AU Lu, FL Liu, YT Inoue, A Suzuki, T Zhao, KJ Zhang, Y AF Lu, Falong Liu, Yuting Inoue, Azusa Suzuki, Tsukasa Zhao, Keji Zhang, Yi TI Establishing Chromatin Regulatory Landscape during Mouse Preimplantation Development SO CELL LA English DT Article ID MASTER TRANSCRIPTION FACTORS; TO-ZYGOTIC TRANSITION; GENE-EXPRESSION; HYPERSENSITIVE SITES; DNA LANDSCAPES; CELL FATE; GENOME; ACCESSIBILITY; EMBRYO; DYNAMICS AB How the chromatin regulatory landscape in the inner cell mass cells is established from differentially packaged sperm and egg genomes during preimplantation development is unknown. Here, we develop a low-input DNase I sequencing (liDNase-seq) method that allows us to generate maps of DNase I-hypersensitive site (DHS) of mouse preimplantation embryos from 1-cell to morula stage. The DHS landscape is progressively established with a drastic increase at the 8-cell stage. Paternal chromatin accessibility is quickly reprogrammed after fertilization to the level similar to maternal chromatin, while imprinted genes exhibit allelic accessibility bias. We demonstrate that transcription factor Nfya contributes to zygotic genome activation and DHS formation at the 2-cell stage and that Oct4 contributes to the DHSs gained at the 8-cell stage. Our study reveals the dynamic chromatin regulatory landscape during early development and identifies key transcription factors important for DHS establishment in mammalian embryos. C1 [Lu, Falong; Liu, Yuting; Inoue, Azusa; Suzuki, Tsukasa; Zhang, Yi] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Lu, Falong; Liu, Yuting; Inoue, Azusa; Suzuki, Tsukasa; Zhang, Yi] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Lu, Falong; Liu, Yuting; Inoue, Azusa; Suzuki, Tsukasa; Zhang, Yi] Boston Childrens Hosp, Div Hematol Oncol, Dept Pediat, Boston, MA 02115 USA. [Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Zhang, Yi] Harvard Stem Cell Inst, WAB 149G,200 Longwood Ave, Boston, MA 02115 USA. [Zhao, Keji] NHLBI, Syst Biol Ctr, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Zhang, Y (reprint author), Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA.; Zhang, Y (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.; Zhang, Y (reprint author), Boston Childrens Hosp, Div Hematol Oncol, Dept Pediat, Boston, MA 02115 USA.; Zhang, Y (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.; Zhang, Y (reprint author), Harvard Stem Cell Inst, WAB 149G,200 Longwood Ave, Boston, MA 02115 USA. EM yzhang@genetics.med.harvard.edu RI Lu, Falong/Q-3013-2016 FU HHMI; Charles A. King Trust FX We thank Dr. Shinpei Yamaguchi for helpful discussion and Dr. Luis Tuesta for critical reading of the manuscript. This project is supported by HHMI. F.L. is supported by a Charles A. King Trust Postdoctoral Research Fellowship. Y.Z. is an investigator of the Howard Hughes Medical Institute. NR 41 TC 9 Z9 9 U1 14 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 JUN 2 PY 2016 VL 165 IS 6 BP 1375 EP 1388 DI 10.1016/j.cell.2016.05.050 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DN4NV UT WOS:000377045400012 PM 27259149 ER PT J AU Jadhav, U Nalapareddy, K Saxena, M O'Neill, NK Pinello, L Yuan, GC Orkin, SH Shivdasani, RA AF Jadhav, Unmesh Nalapareddy, Kodandaramireddy Saxena, Madhurima O'Neill, Nicholas K. Pinello, Luca Yuan, Guo-Cheng Orkin, Stuart H. Shivdasani, Ramesh A. TI Acquired Tissue-Specific Promoter Bivalency Is a Basis for PRC2 Necessity in Adult Cells SO CELL LA English DT Article ID HISTONE METHYLTRANSFERASE ACTIVITY; EMBRYONIC STEM-CELLS; GENOME-WIDE MAPS; CHROMATIN SIGNATURES; EPIGENOMIC LANDSCAPES; GROUND-STATE; SELF-RENEWAL; CHIP-SEQ; LINEAGE; GENE AB Bivalent promoters in embryonic stem cells (ESCs) carry methylation marks on two lysine residues, K4 and K27, in histone3 (H3). K4me2/3 is generally considered to promote transcription, and Polycomb Repressive Complex 2 (PRC2) places K27me3, which is erased at lineage-restricted genes when ESCs differentiate in culture. Molecular defects in various PRC2 null adult tissues lack a unifying explanation. We found that epigenomes in adult mouse intestine and other self-renewing tissues show fewer and distinct bivalent promoters compared to ESCs. Groups of tissue-specific genes that carry bivalent marks are repressed, despite the presence of promoter H3K4me2/3. These are the predominant genes de-repressed in PRC2-deficient adult cells, where aberrant expression is proportional to the H3K4me2/3 levels observed at their promoters in wild-type cells. Thus, in adult animals, PRC2 specifically represses genes with acquired, tissue-restricted promoter bivalency. These findings provide new insights into specificity in chromatin-based gene regulation. C1 [Jadhav, Unmesh; Nalapareddy, Kodandaramireddy; Saxena, Madhurima; O'Neill, Nicholas K.; Shivdasani, Ramesh A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Jadhav, Unmesh; Nalapareddy, Kodandaramireddy; Saxena, Madhurima; O'Neill, Nicholas K.; Shivdasani, Ramesh A.] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. [Jadhav, Unmesh; Nalapareddy, Kodandaramireddy; Saxena, Madhurima; Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Jadhav, Unmesh; Nalapareddy, Kodandaramireddy; Saxena, Madhurima; Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Pinello, Luca; Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Pinello, Luca; Yuan, Guo-Cheng] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Yuan, Guo-Cheng; Orkin, Stuart H.; Shivdasani, Ramesh A.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Orkin, Stuart H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Orkin, Stuart H.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Orkin, Stuart H.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.; Shivdasani, RA (reprint author), Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA.; Shivdasani, RA (reprint author), Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA.; Shivdasani, RA (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA.; Shivdasani, RA (reprint author), Harvard Stem Cell Inst, Cambridge, MA 02138 USA. EM ramesh_shivdasani@dfci.harvard.edu OI Nalapareddy, Kodandaramireddy/0000-0003-3290-5114 FU Intestinal Stem Cell Consortium of the NIDDK [U01DK103152]; NIAID; DFCI-Novartis Drug Discovery Program; NIH [R01DK081113, R01HG005085, F32DK103453, K99HG008399, P50CA127003] FX This work was supported by the Intestinal Stem Cell Consortium (U01DK103152) of the NIDDK and NIAID; the DFCI-Novartis Drug Discovery Program; NIH awards R01DK081113 (R.A.S.), R01HG005085 (G.-C.Y.), F32DK103453 (U.J.), K99HG008399 (L.P.), and P50CA127003; and gifts from the Lind family. We thank Sylvie Robine for Villin-CreER-T2 mice; and Gary Struhl, Jian Xu, Myles Brown, HoMan Chan, Veronica Saenz-Vash, and Huili Zhai for valuable discussions. NR 49 TC 5 Z9 5 U1 8 U2 17 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 JUN 2 PY 2016 VL 165 IS 6 BP 1389 EP 1400 DI 10.1016/j.cell.2016.04.031 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DN4NV UT WOS:000377045400013 PM 27212235 ER PT J AU Kugel, S Sebastian, C Fitamant, J Ross, KN Saha, SK Jain, E Gladden, A Arora, KS Kato, Y Rivera, MN Ramaswamy, S Sadreyev, RI Goren, A Deshpande, V Bardeesy, N Mostoslavsky, R AF Kugel, Sita Sebastian, Carlos Fitamant, Julien Ross, Kenneth N. Saha, Supriya K. Jain, Esha Gladden, Adrianne Arora, Kshitij S. Kato, Yasutaka Rivera, Miguel N. Ramaswamy, Sridhar Sadreyev, Ruslan I. Goren, Alon Deshpande, Vikram Bardeesy, Nabeel Mostoslavsky, Raul TI SIRT6 Suppresses Pancreatic Cancer through Control of Lin28b SO CELL LA English DT Article ID HISTONE DEACETYLASE SIRT6; MESSENGER-RNA; DUCTAL ADENOCARCINOMA; STEM-CELLS; LET-7; EXPRESSION; MICRORNA; PROGRESSION; LIN-28; GENES AB Chromatin remodeling proteins are frequently dysregulated in human cancer, yet little is known about how they control tumorigenesis. Here, we uncover an epigenetic program mediated by the NAD(+)-dependent histone deacetylase Sirtuin 6 (SIRT6) that is critical for suppression of pancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies. SIRT6 inactivation accelerates PDAC progression and metastasis via upregulation of Lin28b, a negative regulator of the let-7 microRNA. SIRT6 loss results in histone hyperacetylation at the Lin28b promoter, Myc recruitment, and pronounced induction of Lin28b and downstream let-7 target genes, HMGA2, IGF2BP1, and IGF2BP3. This epigenetic program defines a distinct subset with a poor prognosis, representing 30%-40% of human PDAC, characterized by reduced SIRT6 expression and an exquisite dependence on Lin28b for tumor growth. Thus, we identify SIRT6 as an important PDAC tumor suppressor and uncover the Lin28b pathway as a potential therapeutic target in a molecularly defined PDAC subset. C1 [Kugel, Sita; Sebastian, Carlos; Fitamant, Julien; Ross, Kenneth N.; Saha, Supriya K.; Arora, Kshitij S.; Kato, Yasutaka; Rivera, Miguel N.; Ramaswamy, Sridhar; Deshpande, Vikram; Bardeesy, Nabeel; Mostoslavsky, Raul] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Kugel, Sita; Sebastian, Carlos; Fitamant, Julien; Ross, Kenneth N.; Saha, Supriya K.; Jain, Esha; Ramaswamy, Sridhar; Bardeesy, Nabeel; Mostoslavsky, Raul] Harvard Univ, Sch Med, MGH Ctr Regenerat Med, Boston, MA 02114 USA. [Gladden, Adrianne; Goren, Alon] Broad Inst Harvard & MIT, BTL, Cambridge, MA 02142 USA. [Sadreyev, Ruslan I.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Sadreyev, Ruslan I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mostoslavsky, Raul] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. RP Mostoslavsky, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA.; Mostoslavsky, R (reprint author), Harvard Univ, Sch Med, MGH Ctr Regenerat Med, Boston, MA 02114 USA.; Mostoslavsky, R (reprint author), Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. EM rmostoslavsky@mgh.harvard.edu FU NIH [CA175727-01, R21CA198109-01, P50CA1270003, P01 CA117969-07, R01 CA133557-05]; National Pancreas Foundation; Linda J. Verville Cancer Research Foundation; Canadian Institutes of Health Research; NCI Mentored Clinical Scientist Research Career Development Award [1K08CA194268-01]; DF/HCC GI SPORE Career Development Project Award [P50CA127003]; Department of Defense; Broad Institute SPARC (Scientific Projects to Accelerate Research and Collaboration) program FX We thank Richard Gregory for the pBabe let-7g 7S21L mutant construct and members of the R.M. and N.B. labs for invaluable discussions and advise. We also thank Cyril Benes for all the human pancreatic cancer lines. This work was supported in part by NIH grants CA175727-01, R21CA198109-01 (to R.M.), P50CA1270003, P01 CA117969-07, and R01 CA133557-05, the National Pancreas Foundation (to R.M.), and the Linda J. Verville Cancer Research Foundation (to N.B.). R.M. is a Kristine and Bob Higgins MGH Research Scholar, a Warshaw Institute Fellow, a Howard Goodman Awardee, and the recipient of the Glenn Award for Research in Biological Mechanisms of Aging. N.B. holds the Gallagher Endowed Chair in Gastrointestinal Cancer Research. N.B. is a member of the Andrew Warshaw Institute for Pancreatic Cancer Research. S.K. is the recipient of a Canadian Institutes of Health Research postdoctoral fellowship. S.K.S. is supported by a NCI Mentored Clinical Scientist Research Career Development Award (1K08CA194268-01) and a DF/HCC GI SPORE Career Development Project Award (P50CA127003). C.S. is supported by the Visionary Postdoctoral Fellowship from the Department of Defense. A.G. is the recipient of the Broad Institute SPARC (Scientific Projects to Accelerate Research and Collaboration) program. NR 50 TC 7 Z9 7 U1 10 U2 21 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 JUN 2 PY 2016 VL 165 IS 6 BP 1401 EP 1415 DI 10.1016/j.cell.2016.04.033 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DN4NV UT WOS:000377045400014 PM 27180906 ER PT J AU Ulirsch, JC Nandakumar, SK Wang, L Giani, FC Zhang, XL Rogov, P Melnikov, A McDonel, P Do, R Mikkelsen, TS Sankaran, VG AF Ulirsch, Jacob C. Nandakumar, Satish K. Wang, Li Giani, Felix C. Zhang, Xiaolan Rogov, Peter Melnikov, Alexandre McDonel, Patrick Do, Ron Mikkelsen, Tarjei S. Sankaran, Vijay G. TI Systematic Functional Dissection of Common Genetic Variation Affecting Red Blood Cell Traits SO CELL LA English DT Article ID DIAMOND-BLACKFAN ANEMIA; GENOME-WIDE ASSOCIATION; IN-VIVO; TERMINAL ERYTHROPOIESIS; SIDEROBLASTIC ANEMIA; MAMMALIAN ENHANCERS; HUMAN HEMATOPOIESIS; NONCODING VARIANTS; DNA-SEQUENCE; EXPRESSION AB Genome-wide association studies (GWAS) have successfully identified thousands of associations between common genetic variants and human disease phenotypes, but the majority of these variants are non-coding, often requiring genetic fine-mapping, epigenomic profiling, and individual reporter assays to delineate potential causal variants. We employ a massively parallel reporter assay (MPRA) to simultaneously screen 2,756 variants in strong linkage disequilibrium with 75 sentinel variants associated with red blood cell traits. We show that this assay identifies elements with endogenous erythroid regulatory activity. Across 23 sentinel variants, we conservatively identified 32 MPRA functional variants (MFVs). We used targeted genome editing to demonstrate endogenous enhancer activity across 3 MFVs that predominantly affect the transcription of SMIM1, RBM38, and CD164. Functional follow-up of RBM38 delineates a key role for this gene in the alternative splicing program occurring during terminal erythropoiesis. Finally, we provide evidence for how common GWAS-nominated variants can disrupt cell-type-specific transcriptional regulatory pathways. C1 [Ulirsch, Jacob C.; Nandakumar, Satish K.; Giani, Felix C.; Sankaran, Vijay G.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Div Hematol Oncol, Boston, MA 02115 USA. [Ulirsch, Jacob C.; Nandakumar, Satish K.; Giani, Felix C.; Sankaran, Vijay G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. [Ulirsch, Jacob C.; Nandakumar, Satish K.; Wang, Li; Giani, Felix C.; Zhang, Xiaolan; Rogov, Peter; Melnikov, Alexandre; McDonel, Patrick; Mikkelsen, Tarjei S.; Sankaran, Vijay G.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Giani, Felix C.] Charite, D-10117 Berlin, Germany. [Do, Ron] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Do, Ron] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA. [Mikkelsen, Tarjei S.; Sankaran, Vijay G.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Sankaran, VG (reprint author), Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Div Hematol Oncol, Boston, MA 02115 USA.; Sankaran, VG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA.; Sankaran, VG (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.; Sankaran, VG (reprint author), Harvard Stem Cell Inst, Cambridge, MA 02138 USA. EM sankaran@broadinstitute.org FU Broad Institute/Boston Children's Hospital collaborative grant; National Institutes of Health [R01 DK103794, R21 HL120791, R01 HG006785] FX We would like to thank members of the Sankaran Lab and numerous colleagues for valuable comments and discussions. This work was supported by a Broad Institute/Boston Children's Hospital collaborative grant and by the National Institutes of Health grants R01 DK103794, R21 HL120791 (to V.G.S.), and R01 HG006785 (to T.S.M.). NR 56 TC 16 Z9 16 U1 6 U2 17 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 JUN 2 PY 2016 VL 165 IS 6 BP 1530 EP 1545 DI 10.1016/j.cell.2016.04.048 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DN4NV UT WOS:000377045400024 PM 27259154 ER PT J AU Rowe, RG Mandelbaum, J Zon, LI Daley, GQ AF Rowe, R. Grant Mandelbaum, Joseph Zon, Leonard I. Daley, George Q. TI Engineering Hematopoietic Stem Cells: Lessons from Development SO CELL STEM CELL LA English DT Review ID GENOME-WIDE ASSOCIATION; VERSUS-HOST-DISEASE; DEFINITIVE HEMATOPOIESIS; YOLK-SAC; SELF-RENEWAL; BONE-MARROW; ADULT HEMATOPOIESIS; CAENORHABDITIS-ELEGANS; MYELOID PROGENITORS; PERIVASCULAR NICHE AB Cell engineering has brought us tantalizingly close to the goal of deriving patient-specific hematopoietic stem cells (HSCs). While directed differentiation and transcription factor-mediated conversion strategies have generated progenitor cells with multilineage potential, to date, therapy-grade engineered HSCs remain elusive due to insufficient long-term self-renewal and inadequate differentiated progeny functionality. A cross-species approach involving zebrafish and mammalian systems offers complementary methodologies to improve understanding of native HSCs. Here, we discuss the role of conserved developmental timing processes in vertebrate hematopoiesis, highlighting how identification and manipulation of stage-specific factors that specify HSC developmental state must be harnessed to engineer HSCs for therapy. C1 [Rowe, R. Grant; Mandelbaum, Joseph; Zon, Leonard I.; Daley, George Q.] Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Rowe, R. Grant; Mandelbaum, Joseph; Zon, Leonard I.; Daley, George Q.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Zon, Leonard I.; Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Zon, Leonard I.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Zon, Leonard I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zon, Leonard I.; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Daley, George Q.] Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA.; Daley, GQ (reprint author), Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.; Daley, GQ (reprint author), Howard Hughes Med Inst, Boston, MA 02115 USA.; Daley, GQ (reprint author), Harvard Stem Cell Inst, Cambridge, MA 02138 USA.; Daley, GQ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.; Daley, GQ (reprint author), Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.; Daley, GQ (reprint author), Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu FU NHLBI NIH HHS [T32 HL007574, U01 HL100001]; NIDDK NIH HHS [R24 DK092760]; NIGMS NIH HHS [R01 GM107536] NR 120 TC 4 Z9 4 U1 9 U2 15 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 JUN 2 PY 2016 VL 18 IS 6 BP 707 EP 720 DI 10.1016/j.stem.2016.05.016 PG 14 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA DN4WK UT WOS:000377067700009 PM 27257760 ER PT J AU Etchegaray, JP Mostoslavsky, R AF Etchegaray, Jean-Pierre Mostoslavsky, Raul TI Interplay between Metabolism and Epigenetics: A Nuclear Adaptation to Environmental Changes SO MOLECULAR CELL LA English DT Review ID REV-ERB-ALPHA; RNA-POLYMERASE-II; HISTONE DEACETYLASE SIRT6; EMBRYONIC STEM-CELLS; O-GLCNAC TRANSFERASE; CONTROLLING MITOCHONDRIAL BIOGENESIS; S-ADENOSYLMETHIONINE SYNTHETASE; CIRCADIAN GENE-EXPRESSION; ACUTE MYELOID-LEUKEMIA; VITAMIN-C AB The physiological identity of every cell is maintained by highly specific transcriptional networks that establish a coherent molecular program that is in tune with nutritional conditions. The regulation of cell-specific transcriptional networks is accomplished by an epigenetic program via chromatin-modifying enzymes, whose activity is directly dependent on metabolites such as acetyl-coenzyme A, S-adenosylmethionine, and NAD+, among others. Therefore, these nuclear activities are directly influenced by the nutritional status of the cell. In addition to nutritional availability, this highly collaborative program between epigenetic dynamics and metabolism is further interconnected with other environmental cues provided by the day-night cycles imposed by circadian rhythms. Herein, we review molecular pathways and their metabolites associated with epigenetic adaptations modulated by histone- and DNA-modifying enzymes and their responsiveness to the environment in the context of health and disease. C1 [Etchegaray, Jean-Pierre; Mostoslavsky, Raul] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Etchegaray, Jean-Pierre; Mostoslavsky, Raul] Harvard Univ, Sch Med, MGH Ctr Regenerat Med, Boston, MA 02114 USA. [Mostoslavsky, Raul] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. RP Mostoslavsky, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA.; Mostoslavsky, R (reprint author), Harvard Univ, Sch Med, MGH Ctr Regenerat Med, Boston, MA 02114 USA.; Mostoslavsky, R (reprint author), Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. EM rmostoslavsky@mgh.harvard.edu FU NIH [CA175727-01, R21CA198109-01, 1R21ES025638-01]; National Pancreas Foundation; Glenn Award for Research in Biological Mechanisms of Aging FX We thank the R.M. lab for critically reading the manuscript, and especially Sam Linder for helpful discussions. Work in the R.M. laboratory is supported in part by NIH grants CA175727-01, R21CA198109-01, and 1R21ES025638-01 and by The National Pancreas Foundation (to R.M.). R.M. is a Kristine and Bob Higgins MGH Research Scholar, a Warshaw Institute Fellow, and the recipient of the Glenn Award for Research in Biological Mechanisms of Aging. NR 210 TC 8 Z9 8 U1 13 U2 35 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD JUN 2 PY 2016 VL 62 IS 5 BP 695 EP 711 DI 10.1016/j.molcel.2016.05.029 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DN4PK UT WOS:000377049500008 PM 27259202 ER PT J AU Nik-Zainal, S Davies, H Staaf, J Ramakrishna, M Dominik, Zou, XQ Martincorena, I Alexandrov, LB Martin, S Wedge, DC Van Loo, P Ju, YS Smid, M Brinkman, AB Morganella, S Aure, MR Lingjaerde, OC Langerod, A Ringner, M Ahn, SM Boyault, S Brock, JE Broeks, A Butler, A Desmedt, C Dirix, L Dronov, S Fatima, A Foekens, JA Gerstung, M Hooijer, GKJ Jang, SJ Jones, DR Kim, HY King, TA Krishnamurthy, S Lee, HJ Lee, JY Li, YL McLaren, S Menzies, A Mustonen, V O'Meara, S Pauporte, I Pivot, X Purdie, CA Raine, K Ramakrishnan, K Rodriguez-Gonzalez, FG Romieu, G Sieuwerts, AM Simpson, PT Shepherd, R Stebbings, L Stefansson, OA Teague, J Tommasi, S Treilleux, I Van den Eynden, GG Vermeulen, P Vincent-Salomon, A Yates, L Caldas, C van't Veer, L Tutt, A Knappskog, S Tan, BKT Jonkers, J Borg, A Ueno, NT Sotiriou, C Viari, A Futreal, PA Campbell, PJ Span, PN Van Laere, S Lakhani, SR Eyfjord, JE Thompson, AM Birney, E Stunnenberg, HG Van De Vijver, MJ Martens, JWM Borresen-Dale, AL Richardson, AL Kong, G Thomas, G Stratton, MR AF Nik-Zainal, Serena Davies, Helen Staaf, Johan Ramakrishna, Manasa Glodzik, Dominik Zou, Xueqing Martincorena, Inigo Alexandrov, Ludmil B. Martin, Sancha Wedge, David C. Van Loo, Peter Ju, Young Seok Smid, Marcel Brinkman, Arie B. Morganella, Sandro Aure, Miriam R. Lingjaerde, Ole Christian Langerod, Anita Ringner, Markus Ahn, Sung-Min Boyault, Sandrine Brock, Jane E. Broeks, Annegien Butler, Adam Desmedt, Christine Dirix, Luc Dronov, Serge Fatima, Aquila Foekens, John A. Gerstung, Moritz Hooijer, Gerrit K. J. Jang, Se Jin Jones, David R. Kim, Hyung-Yong King, Tari A. Krishnamurthy, Savitri Lee, Hee Jin Lee, Jeong-Yeon Li, Yilong McLaren, Stuart Menzies, Andrew Mustonen, Ville O'Meara, Sarah Pauporte, Iris Pivot, Xavier Purdie, Colin A. Raine, Keiran Ramakrishnan, Kamna Rodriguez-Gonzalez, F. German Romieu, Gilles Sieuwerts, Anieta M. Simpson, Peter T. Shepherd, Rebecca Stebbings, Lucy Stefansson, Olafur A. Teague, Jon Tommasi, Stefania Treilleux, Isabelle Van den Eynden, Gert G. Vermeulen, Peter Vincent-Salomon, Anne Yates, Lucy Caldas, Carlos van't Veer, Laura Tutt, Andrew Knappskog, Stian Tan, Benita Kiat Tee Jonkers, Jos Borg, Ake Ueno, Naoto T. Sotiriou, Christos Viari, Alain Futreal, P. Andrew Campbell, Peter J. Span, Paul N. Van Laere, Steven Lakhani, Sunil R. Eyfjord, Jorunn E. Thompson, Alastair M. Birney, Ewan Stunnenberg, Hendrik G. van de Vijver, Marc J. Martens, John W. M. Borresen-Dale, Anne-Lise Richardson, Andrea L. Kong, Gu Thomas, Gilles Stratton, Michael R. TI Landscape of somatic mutations in 560 breast cancer whole-genome sequences SO NATURE LA English DT Article ID TERT PROMOTER MUTATIONS; INVERTED REPEATS; GENE FUSIONS; COPY NUMBER; DNA-REPAIR; TUMORS; SIGNATURES; CARCINOMAS; DISCOVERY; HETEROZYGOSITY AB We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer. C1 [Nik-Zainal, Serena; Davies, Helen; Ramakrishna, Manasa; Glodzik, Dominik; Zou, Xueqing; Martincorena, Inigo; Alexandrov, Ludmil B.; Martin, Sancha; Wedge, David C.; Van Loo, Peter; Ju, Young Seok; Butler, Adam; Dronov, Serge; Gerstung, Moritz; Jones, David R.; Li, Yilong; McLaren, Stuart; Menzies, Andrew; Mustonen, Ville; O'Meara, Sarah; Raine, Keiran; Ramakrishnan, Kamna; Shepherd, Rebecca; Stebbings, Lucy; Teague, Jon; Yates, Lucy; Futreal, P. Andrew; Campbell, Peter J.; Stratton, Michael R.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Nik-Zainal, Serena] Cambridge Univ Hosp NHS Fdn Trust, East Anglian Med Genet Serv, Cambridge CB2 9NB, England. [Staaf, Johan; Ringner, Markus; Borg, Ake] Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22381 Lund, Sweden. [Alexandrov, Ludmil B.] Los Alamos Natl Lab, Theoret Biol & Biophys T6, POB 1663, Los Alamos, NM 87545 USA. [Alexandrov, Ludmil B.] Los Alamos Natl Lab, Ctr Nonlinear Studies, POB 1663, Los Alamos, NM 87545 USA. [Van Loo, Peter] Katholieke Univ Leuven, Dept Human Genet, B-3000 Leuven, Belgium. [Smid, Marcel; Foekens, John A.; Rodriguez-Gonzalez, F. German; Sieuwerts, Anieta M.; Martens, John W. M.] Erasmus Univ, Med Ctr, Erasmus MC Canc Inst, Dept Med Oncol, NL-3015 CN Rotterdam, Netherlands. [Smid, Marcel; Foekens, John A.; Rodriguez-Gonzalez, F. German; Sieuwerts, Anieta M.; Martens, John W. M.] Erasmus Univ, Med Ctr, Canc Genom Netherlands, NL-3015 CN Rotterdam, Netherlands. [Brinkman, Arie B.; Stunnenberg, Hendrik G.] Radboud Univ Nijmegen, Fac Sci, Dept Mol Biol, NL-6525 GA Nijmegen, Netherlands. [Morganella, Sandro; Birney, Ewan] European Bioinformat Inst, European Mol Biol Lab, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England. [Aure, Miriam R.; Langerod, Anita; Borresen-Dale, Anne-Lise] Norwegian Radium Hosp, Oslo Univ Hosp, Inst Canc Res, Dept Canc Genet, N-0310 Oslo, Norway. [Aure, Miriam R.; Lingjaerde, Ole Christian; Langerod, Anita; Borresen-Dale, Anne-Lise] Univ Oslo, Inst Clin Med, KG Jebsen Ctr Breast Canc Res, N-0310 Oslo, Norway. [Lingjaerde, Ole Christian] Univ Oslo, Dept Comp Sci, Oslo, Norway. [Ahn, Sung-Min] Gachon Univ, Gil Med Ctr, Gachon Inst Genome Med & Sci, Inchon, South Korea. [Boyault, Sandrine] Ctr Leon Berard, Translat Res Lab, 28 Rue Laennec, F-69373 Lyon 08, France. [Brock, Jane E.; Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Broeks, Annegien; van't Veer, Laura; Jonkers, Jos] Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands. [Desmedt, Christine; Sotiriou, Christos] Univ Libre Bruxelles, Inst Jules Bordet, Breast Canc Translat Res Lab, Bd Waterloo 121, B-1000 Brussels, Belgium. [Dirix, Luc; Van den Eynden, Gert G.; Vermeulen, Peter; Van Laere, Steven] Univ Antwerp, Fac Med & Hlth Sci, Oncol Res Ctr, Translat Canc Res Unit, B-2020 Antwerp, Belgium. [Fatima, Aquila; Richardson, Andrea L.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Hooijer, Gerrit K. J.; van de Vijver, Marc J.] Univ Amsterdam, Acad Med Ctr, Dept Pathol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. [Jang, Se Jin; Lee, Hee Jin] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Ulsan 680749, South Korea. [Kim, Hyung-Yong; Kong, Gu] Hanyang Univ, Coll Med, Dept Pathol, Seoul 133791, South Korea. [King, Tari A.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. [Krishnamurthy, Savitri; Ueno, Naoto T.] Univ Texas MD Anderson Canc Ctr, Morgan Welch Inflammatory Breast Canc Res Program, 1515 Holcombe Boulevard, Houston, TX 77030 USA. [Lee, Jeong-Yeon] Hanyang Univ, IBBR, Seoul 133791, South Korea. [Pauporte, Iris] Natl Canc Inst, Div Res, Dept Clin Res, 52 Ave Morizet, F-92513 Boulogne, France. [Pivot, Xavier] Univ Hosp Minjoz, INSERM UMR 1098, Bd Fleming, F-25000 Besancon, France. [Purdie, Colin A.; Thompson, Alastair M.] Ninewells Hosp & Med Sch, Dept Pathol, Dundee DD1 9SY, Scotland. [Romieu, Gilles] ICM Inst Reg Canc, Oncol Senol, Montpellier, France. [Simpson, Peter T.; Lakhani, Sunil R.] Univ Queensland, UQ Ctr Clin Res, Brisbane, Qld 4029, Australia. [Simpson, Peter T.; Lakhani, Sunil R.] Univ Queensland, Sch Med, Brisbane, Qld 4029, Australia. [Stefansson, Olafur A.; Eyfjord, Jorunn E.] Univ Iceland, Fac Med, Canc Res Lab, IS-101 Reykjavik, Iceland. [Tommasi, Stefania] IRCCS Ist Tumori Giovanni Paolo II, Bari, Italy. [Treilleux, Isabelle] Ctr Leon Berard, Dept Pathol, 28 Rue Laennec, F-69373 Lyon 08, France. [Van den Eynden, Gert G.; Vermeulen, Peter] GZA Hosp Sint Augustinus, Dept Pathol, Antwerp, Belgium. [Vincent-Salomon, Anne] Paris Sci Lettres Univ, Inst Curie, Dept Pathol, 26 Rue Ulm, F-75248 Paris 05, France. [Vincent-Salomon, Anne] INSERM U934, 26 Rue Ulm, F-75248 Paris 05, France. [Caldas, Carlos] Univ Cambridge, Li Ka Shing Ctr, Canc Res UK Cambridge Inst, Robinson Way, Cambridge CB2 0RE, England. [Tutt, Andrew] Kings Coll London, Breast Canc Now Res Unit, London SE1 9RT, England. [Tutt, Andrew] Inst Canc Res, Breast Canc Now Toby Robins Res Ctr, London SW3 6JB, England. [Knappskog, Stian] Univ Bergen, Dept Clin Sci, N-5020 Bergen, Norway. [Knappskog, Stian] Haukeland Hosp, Dept Oncol, N-5021 Bergen, Norway. [Tan, Benita Kiat Tee] Natl Canc Ctr Singapore, 11 Hosp Dr, Singapore 169610, Singapore. [Tan, Benita Kiat Tee] Singapore Gen Hosp, Outram Rd, Singapore 169608, Singapore. [Viari, Alain] INRIA Grenoble Rhone Alpes, Equipe Erable, 655 Ave Europe, F-38330 Montbonnot St Martin, France. [Viari, Alain; Thomas, Gilles] Ctr Leon Berard, Synergie Lyon Canc, 28 Rue Laennec, F-69373 Lyon 08, France. [Futreal, P. Andrew] UT MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77230 USA. [Span, Paul N.] Radboud Univ Nijmegen, Med Ctr, Dept Radiat Oncol, Dept Lab Med, NL-6525 GA Nijmegen, Netherlands. [Lakhani, Sunil R.] Royal Brisbane & Womens Hosp, Pathol Queensland, Brisbane, Qld 4029, Australia. [Thompson, Alastair M.] Univ Texas MD Anderson Canc Ctr, Dept Breast Surg Oncol, 1400 Pressler St, Houston, TX 77030 USA. RP Nik-Zainal, S; Stratton, MR (reprint author), Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.; Nik-Zainal, S (reprint author), Cambridge Univ Hosp NHS Fdn Trust, East Anglian Med Genet Serv, Cambridge CB2 9NB, England.; Kong, G (reprint author), Hanyang Univ, Coll Med, Dept Pathol, Seoul 133791, South Korea.; Viari, A (reprint author), INRIA Grenoble Rhone Alpes, Equipe Erable, 655 Ave Europe, F-38330 Montbonnot St Martin, France.; Viari, A (reprint author), Ctr Leon Berard, Synergie Lyon Canc, 28 Rue Laennec, F-69373 Lyon 08, France. EM snz@sanger.ac.uk; Alain.Viari@inria.fr; gkong@hanyang.ac.kr; mrs@sanger.ac.uk RI Span, Paul/G-4710-2012; Simpson, Peter/F-1225-2010; Ringner, Markus/G-3641-2011; OI Ahn, Sung-Min/0000-0002-5031-1929; Tommasi, Stefania/0000-0002-2157-2978; Span, Paul/0000-0002-1930-6638; Simpson, Peter/0000-0002-4816-8289; Ringner, Markus/0000-0001-5469-8940; Ramakrishnan, Kamna/0000-0002-2507-4722; Caldas, Carlos/0000-0003-3547-1489; Knappskog, Stian/0000-0002-4153-1655; Ju, Young Seok/0000-0002-5514-4189; Wedge, David/0000-0002-7572-3196; Alexandrov, Ludmil/0000-0003-3596-4515; Desmedt, Christine/0000-0002-5223-5579; Martin, Sancha/0000-0001-6213-5259 FU ICGC Breast Cancer Working group by the Breast Cancer Somatic Genetics Study (BASIS), a European research project - European Community's Seventh Framework Programme [242006]; Triple Negative project - Wellcome Trust [077012/Z/05/Z]; HER2+ project - Institut National du Cancer (INCa) in France [226-2009, 02-2011, 41-2012, 144-2008, 06-2012]; Korean Health Technology R& D Project, Ministry of Health and Welfare, Republic of Korea [A111218-SC01]; BASIS; ICGC breast cancer projects; CRUK; University of Dundee; Chief Scientist Office; Breast Cancer Campaign; Wellcome Trust [WT100183MA]; Los Alamos National Laboratory; Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer [NIH/NCI 5 P50 CA168504-02]; EU-FP7-SUPPRESSTEM project; Cancer Genomics Netherlands through a grant from the Netherlands Organisation of Scientific research (NWO); EU-FP7-DDR response project; Breast Cancer Research Foundation; EMBL; FNRS (Fonds National de la Recherche Scientifique); Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Republic Korea [NRF 2011-0030105]; National Research Foundation of Korea (NRF) - Korean government [NRF 2015R1A2A1A10052578]; ERC Advanced grant [322737]; US Department of Energy National Nuclear Security Administration [DE-AC52-06NA25396]; National Nuclear Security Administration of the United States Department of Energy FX This work has been funded through the ICGC Breast Cancer Working group by the Breast Cancer Somatic Genetics Study (BASIS), a European research project funded by the European Community's Seventh Framework Programme (FP7/2010-2014) under the grant agreement number 242006; the Triple Negative project funded by the Wellcome Trust (grant reference 077012/Z/05/Z) and the HER2+ project funded by Institut National du Cancer (INCa) in France (grant numbers 226-2009, 02-2011, 41-2012, 144-2008, 06-2012). The ICGC Asian Breast Cancer Project was funded through a grant of the Korean Health Technology R& D Project, Ministry of Health and Welfare, Republic of Korea (A111218-SC01). Personally funded by grants above: F.G.R.-G., S.M., K.R., S.M. were funded by BASIS. Recruitment was performed under the auspices of the ICGC breast cancer projects run by the UK, France and Korea. For contributions towards instruments, specimens and collections: Tayside Tissue Bank (funded by CRUK, University of Dundee, Chief Scientist Office & Breast Cancer Campaign), Asan Bio-Resource Center of the Korea Biobank Network, Seoul, South Korea, OSBREAC consortium, The Icelandic Centre for Research (RANNIS), The Swedish Cancer Society and the Swedish Research Council, and Fondation Jean Dausset-Centre d'Etudes du polymorphisme humain. Icelandic Cancer Registry, The Brisbane Breast Bank (The University of Queensland, The Royal Brisbane and Women's Hospital and QIMR Berghofer), Breast Cancer Tissue and Data Bank at KCL and NIHR Biomedical Research Centre at Guy's and St Thomas's Hospitals. Breakthrough Breast Cancer and Cancer Research UK Experimental Cancer Medicine Centre at KCL. For pathology review: The Mouse Genome Project and Department of Pathology, Cambridge University Hospitals NHS Foundation Trust for microscopes. A. Richardson, A. Ehinger, A. Vincent-Salomon, C. Van Deurzen, C. Purdie, D. Larsimont, D. Giri, D. Grabau, E. Provenzano, G. MacGrogan, G. Van den Eynden, I. Treilleux, J. E. Brock, J. Jacquemier, J. Reis-Filho, L. Arnould, L. Jones, M. van de Vijver, O. Garred, R. Salgado, S. Pinder, S. R. Lakhani, T. Sauer, V. Barbashina. Illumina UK Ltd for input on optimization of sequencing throughout this project. Wellcome Trust Sanger Institute Sequencing Core Facility, Core IT Facility and Cancer Genome Project Core IT team and Cancer Genome Project Core Laboratory team for general support. Personal funding: S.N.-Z. is a Wellcome Beit Fellow and personally funded by a Wellcome Trust Intermediate Fellowship (WT100183MA). L.B.A. is supported through a J. Robert Oppenheimer Fellowship at Los Alamos National Laboratory. A.L.R. is partially supported by the Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer (NIH/NCI 5 P50 CA168504-02). D.G. was supported by the EU-FP7-SUPPRESSTEM project. A. S. was supported by Cancer Genomics Netherlands through a grant from the Netherlands Organisation of Scientific research (NWO). M.S. was supported by the EU-FP7-DDR response project. C.S. and C.D. are supported by a grant from the Breast Cancer Research Foundation. E.B. was funded by EMBL. C.S. is funded by FNRS (Fonds National de la Recherche Scientifique). S. J. J. is supported by Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Republic Korea (NRF 2011-0030105). G.K. is supported by National Research Foundation of Korea (NRF) grants funded by the Korean government (NRF 2015R1A2A1A10052578). J.F. received funding from an ERC Advanced grant (no. 322737).; For general contribution and administrative support: Fondation Synergie Lyon Cancer in France. J. G. Jonasson, Department of Pathology, University Hospital & Faculty of Medicine, University of Iceland. K. Ferguson, Tissue Bank Manager, Brisbane Breast Bank and The Breast Unit, The Royal Brisbane and Women's Hospital, Brisbane, Australia. The Oslo Breast Cancer Consortium of Norway (OSBREAC). Angelo Paradiso, IRCCS Istituto Tumori "Giovanni Paolo II", Bari Italy. A. Vines for administratively supporting to identifying the samples, organizing the bank, and sending out the samples. M. Schlooz-Vries, J. Tol, H. van Laarhoven, F. Sweep, P. Bult in Nijmegen for contributions in Nijmegen. This research used resources provided by the Los Alamos National Laboratory Institutional Computing Program, which is supported by the US Department of Energy National Nuclear Security Administration under contract no. DE-AC52-06NA25396. Research performed at Los Alamos National Laboratory was carried out under the auspices of the National Nuclear Security Administration of the United States Department of Energy. N. Miller (in memoriam) for her contribution in setting up the clinical database. Finally, we would like to acknowledge all members of the ICGC Breast Cancer Working Group and ICGC Asian Breast Cancer Project. NR 57 TC 69 Z9 69 U1 35 U2 59 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JUN 2 PY 2016 VL 534 IS 7605 BP 47 EP + DI 10.1038/nature17676 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DN3LB UT WOS:000376962300031 PM 27135926 ER PT J AU Mertins, P Mani, DR Ruggles, KV Gillette, MA Clauser, KR Wang, P Wang, XL Qiao, JW Cao, S Petralia, F Kawaler, E Mundt, F Krug, K Tu, ZD Lei, JT Gatza, ML Wilkerson, M Perou, CM Yellapantula, V Huang, KL Lin, CW McLellan, MD Yan, P Davies, SR Townsend, RR Skates, SJ Wang, J Zhang, B Kinsinger, CR Mesri, M Rodriguez, H Ding, L Paulovich, AG Fenyo, D Ellis, MJ Carr, SA AF Mertins, Philipp Mani, D. R. Ruggles, Kelly V. Gillette, Michael A. Clauser, Karl R. Wang, Pei Wang, Xianlong Qiao, Jana W. Cao, Song Petralia, Francesca Kawaler, Emily Mundt, Filip Krug, Karsten Tu, Zhidong Lei, Jonathan T. Gatza, Michael L. Wilkerson, Matthew Perou, Charles M. Yellapantula, Venkata Huang, Kuan-lin Lin, Chenwei McLellan, Michael D. Yan, Ping Davies, Sherri R. Townsend, R. Reid Skates, Steven J. Wang, Jing Zhang, Bing Kinsinger, Christopher R. Mesri, Mehdi Rodriguez, Henry Ding, Li Paulovich, Amanda G. Fenyo, David Ellis, Matthew J. Carr, Steven A. CA NCI CPTAC TI Proteogenomics connects somatic mutations to signalling in breast cancer SO NATURE LA English DT Article ID ONCOGENIC PIK3CA MUTATIONS; GENE-EXPRESSION SIGNATURES; MOLECULAR PORTRAITS; TUMORS; RECEPTOR; PATHWAYS; PHOSPHORYLATION; HETEROGENEITY; SUBTYPES; REVEALS AB Somatic mutations have been extensively characterized in breast cancer, but the effects of these genetic alterations on the proteomic landscape remain poorly understood. Here we describe quantitative mass-spectrometry-based proteomic and phosphoproteomic analyses of 105 genomically annotated breast cancers, of which 77 provided high-quality data. Integrated analyses provided insights into the somatic cancer genome including the consequences of chromosomal loss, such as the 5q deletion characteristic of basal-like breast cancer. Interrogation of the 5q trans-effects against the Library of Integrated Network-based Cellular Signatures, connected loss of CETN3 and SKP1 to elevated expression of epidermal growth factor receptor (EGFR), and SKP1 loss also to increased SRC tyrosine kinase. Global proteomic data confirmed a stromal-enriched group of proteins in addition to basal and luminal clusters, and pathway analysis of the phosphoproteome identified a G-protein-coupled receptor cluster that was not readily identified at the mRNA level. In addition to ERBB2, other amplicon-associated highly phosphorylated kinases were identified, including CDK12, PAK1, PTK2, RIPK2 and TLK2. We demonstrate that proteogenomic analysis of breast cancer elucidates the functional consequences of somatic mutations, narrows candidate nominations for driver genes within large deletions and amplified regions, and identifies therapeutic targets. C1 [Mertins, Philipp; Mani, D. R.; Gillette, Michael A.; Clauser, Karl R.; Qiao, Jana W.; Mundt, Filip; Krug, Karsten; Carr, Steven A.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Ruggles, Kelly V.; Kawaler, Emily; Fenyo, David] NYU, Langone Med Ctr, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA. [Gillette, Michael A.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Wang, Pei; Petralia, Francesca; Tu, Zhidong] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA. [Wang, Xianlong; Lin, Chenwei; Yan, Ping; Paulovich, Amanda G.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Cao, Song; Yellapantula, Venkata; Huang, Kuan-lin; McLellan, Michael D.; Ding, Li] Washington Univ, Sch Med, Siteman Canc Ctr, Dept Med,McDonnell Genome Inst, St Louis, MO 63108 USA. [Mundt, Filip] Karolinska Inst, Dept Oncol Pathol, S-17176 Stockholm, Sweden. [Lei, Jonathan T.; Ellis, Matthew J.] Baylor Coll Med, Dan L Duncan Comprehens Canc Ctr, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA. [Lei, Jonathan T.; Ellis, Matthew J.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Lei, Jonathan T.; Ellis, Matthew J.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Gatza, Michael L.; Wilkerson, Matthew; Perou, Charles M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA. [Davies, Sherri R.; Townsend, R. Reid] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Skates, Steven J.] Massachusetts Gen Hosp, Ctr Canc, Biostat Ctr, Boston, MA 02114 USA. [Wang, Jing; Zhang, Bing] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37232 USA. [Wang, Jing; Zhang, Bing] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37232 USA. [Kinsinger, Christopher R.; Mesri, Mehdi; Rodriguez, Henry] NCI, NIH, Bethesda, MD 20892 USA. RP Mertins, P; Carr, SA (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.; Ellis, MJ (reprint author), Baylor Coll Med, Dan L Duncan Comprehens Canc Ctr, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.; Ellis, MJ (reprint author), Baylor Coll Med, Dept Med, Houston, TX 77030 USA.; Ellis, MJ (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. EM pmertins@broadinstitute.org; Matthew.Ellis@bcm.edu; scarr@broad.mit.edu OI Lei, Jonathan/0000-0002-0209-8051; Yellapantula, Venkata/0000-0001-9848-3263; Fenyo, David/0000-0001-5049-3825; Ruggles, Kelly/0000-0002-0152-0863 FU National Cancer Institute (NCI) [U24CA160034, U24CA160036, U24CA160019, U24CA159988, U24CA160035]; CPRIT grant [RR140033]; Leidos contract [13XS068]; National Cancer Institute (NCI) CPTAC award [U24CA160035]; NCI Cancer Center Support Grant [P30 CA91842]; NIH/NCRR Washington University-ICTS [UL1 RR024992]; Susan G. Komen for the Cure [KG 090422]; Swedish Research Council [Dnr 2014-323]; [SUB-R01GM108711] FX This work was supported by National Cancer Institute (NCI) CPTAC awards U24CA160034 (Broad Institute; Fred Hutchinson Cancer Research Center), U24CA160036 (Johns Hopkins University), U24CA160019 (Pacific Northwest National Laboratory), U24CA159988 (Vanderbilt University), U24CA160035 (Washington University, St. Louis; University of North Carolina, Chapel Hill). P.W. and F.P. were also supported by SUB-R01GM108711 and MJE by CPRIT grant RR140033. M.J.E. is also a McNair Foundation Scholar. D.F. was supported by Leidos contract 13XS068. Primary genomics data for this study were generated by The Cancer Genome Atlas pilot project established by the NCI and the National Human Genome Research Institute. Resequencing of select samples conducted in this study was supported by National Cancer Institute (NCI) CPTAC award U24CA160035. Information about TCGA and the investigators and institutions that constitute the TCGA research network can be found at http://cancergenome.nih.gov/. We also acknowledge the expert assistance of J. Snider, P. Erdmann-Gilmore and R. Connors for the preparation of the tumour tissues for solubilization. We thank the Alvin J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, for the use of the Tissue Procurement Core, which provided accessioning, histologic processing and review for the TCGA samples included in this study. The Siteman Cancer Center is supported in part by an NCI Cancer Center Support Grant #P30 CA91842 (see more at http://www.siteman.wustl.edu/ContentPage.aspx?id=243#sthash.mEU0QuXx.dpu f). We also thank the HAMLET Core at The Washington University in St. Louis for providing breast cancer xenograft tumors. The HAMLET Core was supported in part by grants from NIH/NCRR Washington University-ICTS (UL1 RR024992) and Susan G. Komen for the Cure (KG 090422). F.M. was also supported by The Swedish Research Council (Dnr 2014-323). We also thank A. Subramanian, C. Flynn and J. Asiedu at the Broad Institute for their guidance and assistance in accessing LINCS to run a large number of enrichment queries. NR 41 TC 45 Z9 46 U1 24 U2 45 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JUN 2 PY 2016 VL 534 IS 7605 BP 55 EP + DI 10.1038/nature18003 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DN3LB UT WOS:000376962300032 PM 27251275 ER PT J AU Jia, Y Yun, CH Park, E Rcan, DE Manuia, M Juarez, J Xu, CX Rhee, K Chen, T Zhang, HK Palakurthi, S Jang, JB Lelais, G DiDonato, M Bursulaya, B Michellys, PY Epple, R Marsilje, TH McNeill, M Lu, WS Harris, J Bender, S Wong, KK Janne, PA Eck, MJ AF Jia, Yong Yun, Cai-Hong Park, Eunyoung Rcan, Dalia E. Manuia, Mari Juarez, Jose Xu, Chunxiao Rhee, Kevin Chen, Ting Zhang, Haikuo Palakurthi, Sangeetha Jang, Jaebong Lelais, Gerald DiDonato, Michael Bursulaya, Badry Michellys, Pierre-Yves Epple, Robert Marsilje, Thomas H. McNeill, Matthew Lu, Wenshuo Harris, Jennifer Bender, Steven Wong, Kwok-Kin Janne, Pasi A. Eck, Michael J. TI Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors SO NATURE LA English DT Article ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; EGFR KINASE; TARGETED THERAPIES; MUTATIONS; GEFITINIB; AZD9291; T790M; DIMERIZATION; SENSITIVITY AB The epidermal growth factor receptor (EGFR)-directed tyrosine kinase inhibitors (TKIs) gefitinib, erlotinib and afatinib are approved treatments for non-small cell lung cancers harbouring activating mutations in the EGFR kinase(1,2), but resistance arises rapidly, most frequently owing to the secondary T790M mutation within the ATP site of the receptor(3,4). Recently developed mutant-selective irreversible inhibitors are highly active against the T790M mutant(5,6), but their efficacy can be compromised by acquired mutation of C797, the cysteine residue with which they form a key covalent bond(7). All current EGFR TKIs target the ATP-site of the kinase, highlighting the need for therapeutic agents with alternative mechanisms of action. Here we describe the rational discovery of EAI045, an allosteric inhibitor that targets selected drug-resistant EGFR mutants but spares the wild-type receptor. The crystal structure shows that the compound binds an allosteric site created by the displacement of the regulatory C-helix in an inactive conformation of the kinase. The compound inhibits L858R/T790M-mutant EGFR with low-nanomolar potency in biochemical assays. However, as a single agent it is not effective in blocking EGFR-driven proliferation in cells owing to differential potency on the two subunits of the dimeric receptor, which interact in an asymmetric manner in the active state(8). We observe marked synergy of EAI045 with cetuximab, an antibody therapeutic that blocks EGFR dimerization(9,10), rendering the kinase uniformly susceptible to the allosteric agent. EAI045 in combination with cetuximab is effective in mouse models of lung cancer driven by EGFR(L858R/T790M) and by EGFR(L858R/T790M/C797S), a mutant that is resistant to all currently available EGFR TKIs. More generally, our findings illustrate the utility of purposefully targeting allosteric sites to obtain mutant-selective inhibitors. C1 [Jia, Yong; Manuia, Mari; Juarez, Jose; Lelais, Gerald; DiDonato, Michael; Bursulaya, Badry; Michellys, Pierre-Yves; Epple, Robert; Marsilje, Thomas H.; McNeill, Matthew; Lu, Wenshuo; Harris, Jennifer; Bender, Steven] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA. [Yun, Cai-Hong; Park, Eunyoung; Jang, Jaebong; Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Yun, Cai-Hong; Park, Eunyoung; Jang, Jaebong; Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Rcan, Dalia E.; Xu, Chunxiao; Rhee, Kevin; Chen, Ting; Zhang, Haikuo; Wong, Kwok-Kin; Janne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA. [Palakurthi, Sangeetha; Wong, Kwok-Kin; Janne, Pasi A.] Dana Farber Canc Inst, Belfer Ctr Appl Canc Sci, Boston, MA 02215 USA. [Yun, Cai-Hong] Peking Univ, Inst Syst Biomed, Beijing 100191, Peoples R China. [Yun, Cai-Hong] Peking Univ, Hlth Sci Ctr, Dept Biophys, Beijing 100191, Peoples R China. RP Eck, MJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.; Eck, MJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM eck@crystal.harvard.edu FU NIH [CA116020, CA154303, CA120964, CA135257]; Gross-Loh Family Fund for Lung Cancer Research FX This work was supported in part by NIH grants CA116020 ( M. J. E.), CA154303 ( M. J. E., K.- K. W. and P. A. J.), CA120964 ( K.- K. W.) and CA135257 ( P. A. J.), and by the Gross-Loh Family Fund for Lung Cancer Research ( K.- K. W.). We thank N. Gray for helpful comments on the manuscript. NR 32 TC 21 Z9 21 U1 22 U2 41 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JUN 2 PY 2016 VL 534 IS 7605 BP 129 EP + DI 10.1038/nature17960 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DN3LB UT WOS:000376962300048 PM 27251290 ER PT J AU Tickell, KD Lokken, EM Schaafsma, TT Goldberg, J Lannon, SMR AF Tickell, Kirkby D. Lokken, Erica M. Schaafsma, Torin T. Goldberg, Jack Lannon, Sophia M. R. TI Lower respiratory tract disorder hospitalizations among children born via elective early-term delivery SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Asthma; bronchiolitis; bronchitis; gestational age; pneumonia ID FETAL LUNG MATURITY; LATE-PRETERM; NEONATAL OUTCOMES; CHILDHOOD ASTHMA; BIRTH; PREGNANCY; ADMISSION; RISK AB Objective: We evaluated the hypothesis that elective early-term delivery increases the risk of childhood lower respiratory tract disorder hospitalization.Methods: Children born via early-term elective inductions were compared to full- or late-term elective inductions in a retrospective cohort study using Washington State birth certificate and hospital discharge data. Outcomes were the odds of lower respiratory disorder hospitalization before age five and cause specific odds ratios for asthma, bronchiolitis, bronchitis, and pneumonia. In addition, a subgroup analysis excluding infants with perinatal complications was conducted.Results: Electively induced early-term children were at significantly increased risk of hospitalization before age five for lower respiratory disorders compared to similar full- or late-term children (adjusted OR: 1.31, 95% CI: 1.11-1.55). Bronchiolitis was the only cause-specific outcome with a statistically significant increase in odds of hospitalization, though comparable increases were found for the less common diagnoses of asthma (adjusted OR: 1.39, 95% CI: 0.93-2.08) and pneumonia (adjusted OR: 1.27, 95% CI: 0.99-1.64). Excluding infants with perinatal complications did not alter the results.Conclusions: There was an association between electively induced early-term delivery and hospitalization for lower respiratory tract disorders before age five. This reinforces policies discouraging elective early-term delivery. C1 [Tickell, Kirkby D.; Lokken, Erica M.; Schaafsma, Torin T.; Goldberg, Jack] Univ Washington, Dept Epidemiol, Box 357236, Seattle, WA 98195 USA. [Goldberg, Jack] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Lannon, Sophia M. R.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. RP Tickell, KD (reprint author), Univ Washington, Dept Epidemiol, Box 357236, Seattle, WA 98195 USA. EM kirkbt@uw.edu NR 19 TC 1 Z9 1 U1 0 U2 14 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD JUN 2 PY 2016 VL 29 IS 11 BP 1871 EP 1876 DI 10.3109/14767058.2015.1066774 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DI5CN UT WOS:000373515800033 PM 26302650 ER PT J AU Wooten, D Guehl, N Yokell, D Shoup, T Zubcevik, N Zafonte, R Johnson, K El Fakhri, G Normandin, M AF Wooten, D. Guehl, N. Yokell, D. Shoup, T. Zubcevik, N. Zafonte, R. Johnson, K. El Fakhri, G. Normandin, M. TI PHARMACOKINETIC EVALUATION OF THE TAU RADIOTRACER [18F]T807 WITH ARTERIAL KINETIC ANALYSIS SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Wooten, D.; Guehl, N.; Yokell, D.; Shoup, T.; El Fakhri, G.; Normandin, M.] Massachusetts Gen Hosp, CAMIS Radiol, Boston, MA 02114 USA. [Wooten, D.; Guehl, N.; Yokell, D.; Shoup, T.; Johnson, K.; El Fakhri, G.; Normandin, M.] Harvard Med Sch, Boston, MA USA. [Zubcevik, N.; Zafonte, R.] Spaulding Rehabil Hosp, Phys Med & Rehabil, Boston, MA USA. [Johnson, K.] Massachusetts Gen Hosp, Radiol, Boston, MA 02114 USA. FU [R01MH068376]; [R01MH095809]; [T32EB013180] FX R01MH068376, R01MH095809, T32EB013180Figure 1: [18F]T807 arterial kinetics. ( Top) %PPF and (Bottom) [18F]T807 arterial time course. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 65 BP 18 EP 19 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300027 ER PT J AU Ayata, C AF Ayata, C. TI Supply-demand mismatch transients trigger spreading depolarizations within penumbral hot-zones SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Ayata, C.] Massachusetts Gen Hosp, Neurol & Radiol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 112 BP 52 EP 52 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300060 ER PT J AU Guehl, N Wooten, W El Fakhri, G Alpert, N Normandin, M AF Guehl, N. Wooten, W. El Fakhri, G. Alpert, N. Normandin, M. TI MEASUREMENT OF DOPAMINE RELEASE WITH PET/FMRI SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Guehl, N.; Wooten, W.; El Fakhri, G.; Alpert, N.; Normandin, M.] Harvard Med Sch, Massachusetts Gen Hosp, Radiol, Boston, MA USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 149 BP 74 EP 75 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300086 ER PT J AU Wey, H Hooker, J Placzek, M Rosen, B Mandeville, J AF Wey, H. Hooker, J. Placzek, M. Rosen, B. Mandeville, J. TI SIMULTANEOUS PET/MRI MEASUREMENTS OF HEMODYNAMIC RESPONSE TO mu-OPIOID RECEPTOR OCCUPANCY SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Wey, H.; Hooker, J.; Placzek, M.; Rosen, B.; Mandeville, J.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 173 BP 90 EP 91 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300103 ER PT J AU Linfante, I Walker, GR Starosciak, AK Dabus, G Yoo, AJ Britz, GW Abou-Chebl, A Castonguay, AC Alvarez, A Gupta, R Mueller-Kronast, N English, JD Malisch, TW Xavier, A Rai, AT Froehler, MT Nguyen, TN Novakovic, R Nogueira, RG Zaidat, OO AF Linfante, I. Walker, G. R. Starosciak, A. K. Dabus, G. Yoo, A. J. Britz, G. W. Abou-Chebl, A. Castonguay, A. C. Alvarez, A. Gupta, R. Mueller-Kronast, N. English, J. D. Malisch, T. W. Xavier, A. Rai, A. T. Froehler, M. T. Nguyen, T. N. Novakovic, R. Nogueira, R. G. Zaidat, O. O. TI PREDICTORS OF MORTALITY IN ACUTE ISCHEMIC STROKE INTERVENTION: ANALYSIS OF THE NASA REGISTRY SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Linfante, I.; Dabus, G.; Alvarez, A.; English, J. D.; Malisch, T. W.; Xavier, A.; Rai, A. T.; Froehler, M. T.; Nguyen, T. N.; Novakovic, R.; Zaidat, O. O.] Baptist Hlth South Florida, Miami Cardiac & Vasc Inst, Miami, FL USA. [Walker, G. R.; Xavier, A.] Baptist Hlth South Florida, Ctr Res & Grants, Miami, FL USA. [Starosciak, A. K.; Rai, A. T.] Baptist Hlth South Florida, Neurosci Ctr, Miami, FL USA. [Yoo, A. J.; Froehler, M. T.] Massachusetts Gen Hosp, Radiol Div Diagnost & Intervent Neuroradiol, Boston, MA 02114 USA. [Britz, G. W.; Nguyen, T. N.] Methodist Neurol Inst, Neurosurg, Houston, TX USA. [Abou-Chebl, A.; Novakovic, R.] Baptist Hlth Louisville, Neurol, Louisville, KY USA. [Castonguay, A. C.; Zaidat, O. O.] Froedtert Hosp, Med Coll Wisconsin, Neurol, Milwaukee, WI USA. [Gupta, R.; Nogueira, R. G.] Emory Univ, Sch Med, Neurol, Atlanta, GA USA. [Mueller-Kronast, N.] Delray Med Ctr, Neurol, Delray Beach, FL USA. Calif Pacific Med Ctr, Neurointervent Serv, San Francisco, CA USA. Alexian Bros Med Ctr, Elk Grove Village, IL USA. Wayne State Univ, Sch Med, Neurol, Detroit, MI USA. West Virginia Univ Hosp, Radiol, Morgantown, WV USA. Vanderbilt Univ, Med Ctr, Neurol Neurosurg & Radiol, Nashville, TN USA. Boston Med Ctr, Neurol Neurosurg & Radiol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 180 BP 95 EP 96 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300108 ER PT J AU Normandin, MD Wooten, DW Goer, F Beltzer, M Vitaliano, G Brennan, B Brooks, N Crowley, D Alpert, NM El Fakhri, G Pizzagalli, DA AF Normandin, M. D. Wooten, D. W. Goer, F. Beltzer, M. Vitaliano, G. Brennan, B. Brooks, N. Crowley, D. Alpert, N. M. El Fakhri, G. Pizzagalli, D. A. TI DECREASED DOPAMINE TRANSPORTER EXPRESSION IN MAJOR DEPRESSIVE DISORDER MEASURED WITH [11C]ALTROPANE PET SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Normandin, M. D.; Wooten, D. W.; Alpert, N. M.; El Fakhri, G.] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. [Normandin, M. D.; Wooten, D. W.; Alpert, N. M.; El Fakhri, G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Normandin, M. D.; Wooten, D. W.; Alpert, N. M.; El Fakhri, G.] Harvard Med Sch, Boston, MA USA. [Goer, F.; Beltzer, M.; Brooks, N.; Crowley, D.; Pizzagalli, D. A.] McLean Hosp, Ctr Depress Anxiety & Stress Res, 115 Mill St, Belmont, MA 02178 USA. [Vitaliano, G.; Pizzagalli, D. A.] McLean Hosp, McLean Imaging Ctr, 115 Mill St, Belmont, MA 02178 USA. [Vitaliano, G.; Brennan, B.; Pizzagalli, D. A.] Harvard Med Sch, Belmont, MA USA. [Brennan, B.] McLean Hosp, Biol Psychiat Lab, 115 Mill St, Belmont, MA 02178 USA. FU [R01MH068376]; [R01MH095809]; [T32EB013180] FX Research Support: R01MH068376, R01MH095809, T32EB013180 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 220 BP 126 EP 126 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300138 ER PT J AU Sander, CY Hooker, JM Catana, C Rosen, BR Mandeville, JB AF Sander, C. Y. Hooker, J. M. Catana, C. Rosen, B. R. Mandeville, J. B. TI ASSESSING RECEPTOR DESENSITIZATION AND INTERNALIZATION PARAMETERS WITH SIMULTANEOUS PET/FMRI SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Sander, C. Y.; Hooker, J. M.; Catana, C.; Rosen, B. R.; Mandeville, J. B.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 231 BP 130 EP 131 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300143 ER PT J AU Sakadzic, S AF Sakadzic, S. TI Imaging the cerebral microcirculation and oxygenationIMAGING THE CEREBRAL MICROCIRCULATION AND OXYGENATION SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Sakadzic, S.] Massachusetts Gen Hosp, Martinos Ctr Opt Div, Charlestown, MA USA. [Sakadzic, S.] Harvard Med Sch, Charlestown, MA USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 243 BP 137 EP 138 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300151 ER PT J AU Dehaes, M Cheng, H Ferradal, S Buckley, E Lin, P Vyas, R Hagan, K Wigmore, D McDavitt, E Fenoglio, A Boas, DA Soul, J Franceschini, MA Newburger, JW Grant, PE AF Dehaes, M. Cheng, H. Ferradal, S. Buckley, E. Lin, P. Vyas, R. Hagan, K. Wigmore, D. McDavitt, E. Fenoglio, A. Boas, D. A. Soul, J. Franceschini, M. A. Newburger, J. W. Grant, P. E. TI PERIOPERATIVE CEREBRAL HEMODYNAMICS AND METABOLISM IN NEONATES WITH SINGLE-VENTRICLE PHYSIOLOGY SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Dehaes, M.; Ferradal, S.; Vyas, R.; Hagan, K.; Fenoglio, A.; Grant, P. E.] Harvard Med Sch, Boston Childrens Hosp, Med, Boston, MA USA. [Cheng, H.; Wigmore, D.; McDavitt, E.; Newburger, J. W.] Harvard Med Sch, Boston Childrens Hosp, Cardiol, Boston, MA USA. [Buckley, E.; Lin, P.; Boas, D. A.; Franceschini, M. A.] Harvard Med Sch, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Radiol, Charlestown, MA USA. [Soul, J.] Harvard Med Sch, Boston Childrens Hosp, Neurol, Boston, MA USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 281 BP 162 EP 163 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300178 ER PT J AU Lin, P Sutin, J Cornelissen, L Chen, K Grant, P Berde, C Franceschini, M AF Lin, P. Sutin, J. Cornelissen, L. Chen, K. Grant, P. Berde, C. Franceschini, M. TI INTRAOPERATIVE MEASURES OF CEREBRAL PERFUSION AND OXYGEN CONSUMPTION IN ANAESTHETIZED INFANTS USING DIFFUSE CORRELATION SPECTROSCOPY AND NEAR-INFRARED SPECTROSCOPY SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract ID ANESTHESIA C1 [Lin, P.; Sutin, J.; Franceschini, M.] Harvard Med Sch, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Cornelissen, L.; Chen, K.; Berde, C.] Harvard Med Sch, Boston Children Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA. [Grant, P.] Harvard Med Sch, Boston Children Hosp, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 371 BP 237 EP 237 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300258 ER PT J AU Lin, P Hagan, K Vyas, R Warf, B Grant, P Franceschini, M AF Lin, P. Hagan, K. Vyas, R. Warf, B. Grant, P. Franceschini, M. TI BEDSIDE MEASURES OF CEREBRAL BLOOD FLOW AND OXYGEN CONSUMPTION CHANGES IN NEWBORNS WITH HYDROCEPHALUS TREATED BY ENDOSCOPIC THIRD VENTRICULOSTOMY COMBINED WITH CHOROID PLEXUS CAUTERIZATION SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract ID HEMODYNAMICS C1 [Lin, P.; Hagan, K.; Franceschini, M.] Harvard Med Sch, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Vyas, R.; Grant, P.] Harvard Med Sch, Boston Children Hosp, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA USA. [Warf, B.] Harvard Med Sch, Boston Children Hosp, Dept Neurosurg, Boston, MA USA. [Warf, B.] Harvard Med Sch, Boston Children Hosp, Dept Global Hlth & Social Med, Boston, MA USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 372 BP 238 EP 238 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300259 ER PT J AU Buckley, E Miller, B Golinski, JM Sadeghian, H McAllister, LM Ayata, C Meehan, WP Franceschini, MA Whalen, MJ AF Buckley, E. Miller, B. Golinski, J. M. Sadeghian, H. McAllister, L. M. Ayata, C. Meehan, W. P. Franceschini, M. A. Whalen, M. J. TI DECREASED CEREBRAL BLOOD FLOW IS ASSOCIATED WITH WORSE COGNITIVE OUTCOME AFTER REPETITIVE CONCUSSIONS IN MICE SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Buckley, E.] Georgia Inst Technol, Biomed Engn, Atlanta, GA 30332 USA. [Miller, B.; Sadeghian, H.; Ayata, C.; Franceschini, M. A.] Massachusetts Gen Hosp, Radiol, Boston, MA 02114 USA. [Golinski, J. M.; McAllister, L. M.; Whalen, M. J.] Massachusetts Gen Hosp, Pediat, Boston, MA 02114 USA. [Meehan, W. P.] Boston Childrens Hosp, Sports Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 377 BP 242 EP 243 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300264 ER PT J AU Shindo, A Maki, T Mandeville, ET Itoh, K Ling, AC Itoh, N Borlongan, M Holder, JC Chuang, TT McNeish, JD Tomimoto, H Lok, J Lo, EH Arai, KEN AF Shindo, A. Maki, T. Mandeville, E. T. Itoh, K. Ling, A. C. Itoh, N. Borlongan, M. Holder, J. C. Chuang, T. T. McNeish, J. D. Tomimoto, H. Lok, J. Lo, E. H. Arai, K. E. N. TI ASTROCYTE-DERIVED PENTRAXIN 3 SUPPORTS BLOOD-BRAIN BARRIER INTEGRITY SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Shindo, A.; Maki, T.; Mandeville, E. T.; Itoh, K.; Ling, A. C.; Itoh, N.; Borlongan, M.; Lo, E. H.; Arai, K. E. N.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA USA. [Shindo, A.; Maki, T.; Mandeville, E. T.; Itoh, K.; Ling, A. C.; Itoh, N.; Borlongan, M.; Lo, E. H.; Arai, K. E. N.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA USA. [Shindo, A.; Maki, T.; Mandeville, E. T.; Itoh, K.; Ling, A. C.; Itoh, N.; Borlongan, M.; Lok, J.; Lo, E. H.; Arai, K. E. N.] Harvard Med Sch, Charlestown, MA USA. [Holder, J. C.; Chuang, T. T.; McNeish, J. D.] GlaxoSmithKline, Dept Vasc Biol, Harlow, Essex, England. [Tomimoto, H.] Mie Univ, Grad Sch Med, Dept Neurol, Tsu, Mie, Japan. [Lok, J.] Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 401 BP 267 EP 267 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300288 ER PT J AU Miyamoto, N Maki, T Hayakawa, K Lo, EH Arai, K Urabe, T AF Miyamoto, N. Maki, T. Hayakawa, K. Lo, E. H. Arai, K. Urabe, T. TI EDARAVONE PROTECTS CEREBRAL WHITE MATTER AGAINST CHRONIC HYPOXIC STRESS THROUGH ENHANCING OLIGODENDROGENESIS SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Miyamoto, N.; Urabe, T.] Juntendo Univ, Urayasu Hosp, Neurol, Urayasu, Japan. [Maki, T.; Hayakawa, K.; Lo, E. H.; Arai, K.] Massachusetts Gen Hosp, Radiol, Charlestown, MA USA. [Maki, T.; Hayakawa, K.; Lo, E. H.; Arai, K.] Harvard Med Sch, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 453 BP 313 EP 313 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300340 ER PT J AU Xing, C Wu, L Leung, W Lok, J Lo, EH AF Xing, C. Wu, L. Leung, W. Lok, J. Lo, E. H. TI EFFECTS OF LIPOCALIN-2 IN THE REGULATION OF GLIAL ACTIVATION AND ANGIOGENESIS SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Xing, C.; Wu, L.; Leung, W.; Lok, J.; Lo, E. H.] Massachusetts Gen Hosp, Radiol & Neurol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 464 BP 322 EP 322 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300351 ER PT J AU Sharma, H Nozari, A Muresanu, D Moessler, H Lafuente, J Sharma, A AF Sharma, H. Nozari, A. Muresanu, D. Moessler, H. Lafuente, J. Sharma, A. TI NANOPARTICLES FROM METALS EXACERBATE CARDIAC ARREST INDUCED BRAIN PATHOLOGY. NEUROPROTECTIVE EFFECTS OF CEREBROLYSIN SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Sharma, H.] Uppsala Univ Hsopital, Surg Sci Anesthesiol Intens Care Med, Uppsala, Sweden. [Nozari, A.] Massachusetts Gen Hosp, Anesthesiol & Intens Care Med, Boston, MA 02114 USA. [Muresanu, D.] Univ Med & Pharm, Clin Neurosci, Cluj Napoca, Romania. [Moessler, H.] Ever Neuro Pharma, Drug Dev & Discovery, Oberburgau, Austria. [Lafuente, J.] Univ Basque Country, Neurosci, Bilbao, Spain. [Sharma, A.] Uppsala Univ, Univ Hosp, Surg Sci Anesthesiol & Intens Care Med, Uppsala, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 476 BP 332 EP 333 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300363 ER PT J AU Oka, F Chen, SP Hoffmann, U Lee, JH Hopson, KP Yuzawa, I Qin, T Ayata, C AF Oka, F. Chen, S. P. Hoffmann, U. Lee, J. H. Hopson, K. P. Yuzawa, I. Qin, T. Ayata, C. TI SPREADING INJURY DEPOLARIZATIONS AND THE INTERFACE BETWEEN SUBARACHNOID HEMORRHAGE AND CEREBRAL ISCHEMIA SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Oka, F.; Chen, S. P.; Hoffmann, U.; Lee, J. H.; Hopson, K. P.; Yuzawa, I.; Qin, T.] Massachusetts Gen Hosp, Radiol, Charlestown, MA USA. [Ayata, C.] Massachusetts Gen Hosp, Radiol & Neurol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 504 BP 360 EP 361 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300391 ER PT J AU Oka, F Atalay, YB Qin, T Ayata, C AF Oka, F. Atalay, Y. B. Qin, T. Ayata, C. TI COGNITIVE DYSFUNCTION IN A PRE-CHIASMATIC CISTERN BLOOD INJECTION MODEL OF ANEURYSMAL SUBARACHNOID HEMORRHAGE IN MICE SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Oka, F.; Atalay, Y. B.; Qin, T.] Massachusetts Gen Hosp, Radiol, Charlestown, MA USA. [Ayata, C.] Massachusetts Gen Hosp, Radiol & Neurol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 505 BP 361 EP 361 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300392 ER PT J AU Wang, H Boas, D Akkin, T AF Wang, H. Boas, D. Akkin, T. TI RECONSTRUCTION OF DEPTH-RESOLVED FIBER ORIENTATIONS IN THE BRAIN WITH POLARIZATION SENSITIVE OPTICAL COHERENCE TOMOGRAPHY SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Wang, H.; Boas, D.] Harvard Med Sch, Massachusetts Gen Hosp, Radiol, Charlestown, MA USA. [Akkin, T.] Univ Minnesota, Biomed Engn, Minneapolis, MN USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 533 BP 388 EP 389 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300420 ER PT J AU Yaseen, MA Sakadzic, S Wu, W Fu, B Boas, DA AF Yaseen, M. A. Sakadzic, S. Wu, W. Fu, B. Boas, D. A. TI ASSESSING THE SIGNIFICANCE OF MULTIPLE ENZYME-BOUND FORMULATIONS OF CEREBRAL NADH RESOLVED BY IN VIVO 2-PHOTON LIFETIME MICROSCOPY SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Yaseen, M. A.; Sakadzic, S.; Wu, W.; Fu, B.; Boas, D. A.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 534 BP 390 EP 390 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300421 ER PT J AU Carp, SA Boas, DA Evans, KC Chen, ST Selb, J AF Carp, S. A. Boas, D. A. Evans, K. C. Chen, S. -T. Selb, J. TI IMPROVED ACCURACY OF DIFFUSE CORRELATION SPECTROSCOPY BRAIN PERFUSION MEASUREMENTS USING MULTI-DISTANCE MEASUREMENTS IN CONJUNCTION WITH A MONTE CARLO LIGHT TRANSPORT MODEL SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Carp, S. A.; Boas, D. A.; Chen, S. -T.; Selb, J.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Evans, K. C.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 536 BP 392 EP 393 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300423 ER PT J AU Atochin, D Zaitsev, S Carnemolla, R Muzykantov, V Huang, PL AF Atochin, D. Zaitsev, S. Carnemolla, R. Muzykantov, V. Huang, P. L. TI TARGETING RECOMBINANT THROMBOMODULIN FUSION PROTEIN TO RED BLOOD CELLS PROTECTS AGAINST STROKE SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Atochin, D.; Huang, P. L.] Massachusetts Gen Hosp, Dept Med Cardiol, Cardiovasc Res Ctr, Charlestown, MA USA. [Zaitsev, S.; Carnemolla, R.; Muzykantov, V.] Univ Penn, Dept Pharmacol, Ctr Targeted Therapeut & Translat Nanomed ITMAT C, Translat Res Ctr, Philadelphia, PA 19104 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 586 BP 440 EP 441 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300473 ER PT J AU Buckley, E Patel, SD Miller, BF Franceschini, MA Vannucci, SJ AF Buckley, E. Patel, S. D. Miller, B. F. Franceschini, M. A. Vannucci, S. J. TI IN VIVO MONITORING OF CEREBRAL HEMODYNAMICS IN THE IMMATURE RAT: EFFECTS OF HYPOXIA-ISCHEMIA AND HYPOTHERMIA SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Buckley, E.] Georgia Inst Technol, Biomed Engn, Atlanta, GA 30332 USA. [Patel, S. D.; Vannucci, S. J.] Weill Cornell Med Sch, Pediat Newborn Med, New York, NY USA. [Miller, B. F.; Franceschini, M. A.] Massachusetts Gen Hosp, Radiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 590 BP 444 EP 445 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300477 ER PT J AU Oka, F Lee, JH Yuzawa, I Bornstadt, DV Qin, T Eikermann-Haerter, K Joutel, A Ayata, C AF Oka, F. Lee, J. H. Yuzawa, I. Bornstadt, D. V. Qin, T. Eikermann-Haerter, K. Joutel, A. Ayata, C. TI CADASIL MUTATIONS INCREASE STROKE VULNERABILITY SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Oka, F.; Lee, J. H.; Yuzawa, I.; Bornstadt, D. V.; Qin, T.; Eikermann-Haerter, K.] Massachusetts Gen Hosp, Radiol, Charlestown, MA USA. [Joutel, A.] INSERM, Med, Paris, France. [Joutel, A.] Univ Paris Diderot, Paris, France. [Ayata, C.] Massachusetts Gen Hosp, Radiol & Neurol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 615 BP 468 EP 468 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956300502 ER PT J AU von Bornstadt, D Houben, M Seidel, J Zheng, Y Dilekoz, E Qin, T Sandow, N Sreekanth, K Eikermann-Haerter, K Endres, M Boas, D Moskowitz, MA Lo, EH Dreier, JP Woitzik, J Sakadzic, S Ayata, C AF von Bornstaedt, D. Houben, M. Seidel, J. Zheng, Y. Dilekoz, E. Qin, T. Sandow, N. Sreekanth, K. Eikermann-Haerter, K. Endres, M. Boas, D. Moskowitz, M. A. Lo, E. H. Dreier, J. P. Woitzik, J. Sakadzic, S. Ayata, C. TI SUPPLY-DEMAND MISMATCH TRANSIENTS TRIGGER PERI-INFARCT DEPOLARIZATIONS IN ISCHEMIC PENUMBRA SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract ID SPREADING DEPOLARIZATIONS; STROKE C1 [von Bornstaedt, D.; Houben, M.; Ayata, C.] Harvard Med Sch, Massachusetts Gen Hosp, Neurol & Radiol, Boston, MA USA. [von Bornstaedt, D.] Charite, Berlin, Germany. [Houben, M.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Seidel, J.; Zheng, Y.; Qin, T.; Eikermann-Haerter, K.; Moskowitz, M. A.; Lo, E. H.] Harvard Med Sch, Massachusetts Gen Hosp, Radiol, Boston, MA USA. [Dilekoz, E.] Harvard Med Sch, Massachusetts Gen Hosp, Radiol & Pharmacol, Boston, MA USA. [Dilekoz, E.] Gazi Univ, Fac Med, Ankara, Turkey. [Sandow, N.; Woitzik, J.] Charite, Neurosurg, Berlin, Germany. [Sreekanth, K.; Boas, D.; Sakadzic, S.] Harvard Med Sch, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Endres, M.; Dreier, J. P.] Charite, Neurol, Berlin, Germany. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 706 BP 545 EP 546 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956301080 ER PT J AU Maki, T Maeda, M Uemura, M Lo, E Terasaki, Y Liang, A Shindo, A Takahashi, R Ihara, M Arai, K AF Maki, T. Maeda, M. Uemura, M. Lo, E. Terasaki, Y. Liang, A. Shindo, A. Takahashi, R. Ihara, M. Arai, K. TI PERICYTES INTERACT WITH OLIGODENDROCYTE PRECURSOR CELLS IN PERIVASCULAR REGION IN CEREBRAL WHITE MATTER SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Maki, T.; Lo, E.; Terasaki, Y.; Liang, A.; Shindo, A.; Arai, K.] Massachusetts Gen Hosp, Neurol & Radiol, Charlestown, MA USA. [Maeda, M.] Inst Biomed Res & Innovat, Regenerat Med, Kobe, Hyogo, Japan. [Uemura, M.; Takahashi, R.] Kyoto Univ, Neurol, Kyoto, Japan. [Ihara, M.] Natl Cerebral & Cardiovasc Ctr, Stroke & Cerebrovasc Dis, Osaka, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 745 BP 582 EP 582 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956301119 ER PT J AU Wooten, D Mandeville, J Hooker, J El Fakhri, G Alpert, N Normandin, M AF Wooten, D. Mandeville, J. Hooker, J. El Fakhri, G. Alpert, N. Normandin, M. TI DOPAMINE D1 LIGANDS SCH23390 AND NNC112 EXHIBIT PARTIAL AGONISTIC PROPERTIES AS MEASURED IN VIVO SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Wooten, D.; El Fakhri, G.; Alpert, N.; Normandin, M.] Harvard Med Sch, Massachusetts Gen Hosp, CAMIS Radiol, Boston, MA USA. [Mandeville, J.; Hooker, J.] Harvard Med Sch, Massachusetts Gen Hosp, Martinos Ctr, Boston, MA USA. FU [NIH-R01MH100350]; [NIH-R21NS072148]; [NIH-T32EB013180] FX NIH-R01MH100350, NIH-R21NS072148, NIH-T32EB013180 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 835 BP 668 EP 669 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956301209 ER PT J AU Normandin, MD Wooten, DW Zhang, X Ebrahimi, B Huang, C Atassi, N Johnson, KA Zubcevik, N Zafonte, RD El Fakhri, G AF Normandin, M. D. Wooten, D. W. Zhang, X. Ebrahimi, B. Huang, C. Atassi, N. Johnson, K. A. Zubcevik, N. Zafonte, R. D. El Fakhri, G. TI [18F]T807 PET AND DIFFUSION TENSOR IMAGING REVEAL ASSOCIATION BETWEEN TAU PATHOLOGY AND NEURONAL FIBER INTEGRITY IN TRAUMATIC BRAIN INJURY SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Normandin, M. D.; Wooten, D. W.; Zhang, X.; Ebrahimi, B.; Huang, C.; El Fakhri, G.] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Boston, MA USA. [Normandin, M. D.; Wooten, D. W.; Zhang, X.; Ebrahimi, B.; Huang, C.; Johnson, K. A.; El Fakhri, G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Normandin, M. D.; Wooten, D. W.; Zhang, X.; Ebrahimi, B.; Huang, C.; Atassi, N.; Johnson, K. A.; Zubcevik, N.; Zafonte, R. D.; El Fakhri, G.] Harvard Med Sch, Boston, MA USA. [Atassi, N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Zubcevik, N.; Zafonte, R. D.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 865 BP 694 EP 695 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956301239 ER PT J AU Kisler, K Rege, SV Nelson, AR Ramanathan, A Ahuja, A Tsai, PS Boas, DA Sakadzic, S Zlokovic, BZ AF Kisler, K. Rege, S. V. Nelson, A. R. Ramanathan, A. Ahuja, A. Tsai, P. S. Boas, D. A. Sakadzic, S. Zlokovic, B. Z. TI PERICYTE REGULATION OF NEUROVASCULAR COUPLING AND OXYGEN SUPPLY TO THE BRAIN SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract ID BLOOD-FLOW; DISEASE; BARRIER; HEALTH C1 [Kisler, K.; Rege, S. V.; Nelson, A. R.; Ramanathan, A.; Ahuja, A.; Zlokovic, B. Z.] Univ Southern Calif, Dept Physiol & Biophys, Los Angeles, CA USA. [Kisler, K.; Rege, S. V.; Nelson, A. R.; Ramanathan, A.; Ahuja, A.; Zlokovic, B. Z.] Univ Southern Calif, Zilkha Neurogenet Insitute, Los Angeles, CA USA. [Tsai, P. S.] Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA. [Boas, D. A.; Sakadzic, S.] Massachusetts Gen Hosp, Dept Radiol, Opt Div, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Boas, D. A.; Sakadzic, S.] Harvard Med Sch, Charlestown, MA USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 885 BP 710 EP 710 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956301259 ER PT J AU Sakadzic, S Vinogradov, SA Boas, DA AF Sakadzic, S. Vinogradov, S. A. Boas, D. A. TI FACILITATING THE ADOPTION OF OXYGEN PARTIAL PRESSURE IMAGING WITH TWO-PHOTON MICROSCOPY SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Sakadzic, S.; Boas, D. A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Opt Div, Charlestown, MA 02129 USA. [Sakadzic, S.; Boas, D. A.] Harvard Med Sch, Charlestown, MA 02129 USA. [Vinogradov, S. A.] Univ Penn, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 906 BP 727 EP 728 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956301280 ER PT J AU Selb, J Sutin, J Lin, PI Bechek, SC Boas, DA Franceschini, MA Rosenthal, ES AF Selb, J. Sutin, J. Lin, P. I. Bechek, S. C. Boas, D. A. Franceschini, M. A. Rosenthal, E. S. TI FEASIBILITY OF DIFFUSE CORRELATION SPECTROSCOPY FOR PROLONGED MONITORING OF CEREBRAL AUTOREGULATION DURING NEUROCRITICAL CARE SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Selb, J.; Sutin, J.; Lin, P. I.; Boas, D. A.; Franceschini, M. A.] Massachusetts Gen Hosp, Radiol, Charlestown, MA USA. [Bechek, S. C.; Rosenthal, E. S.] Massachusetts Gen Hosp, Neurol, Charlestown, MA USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 908 BP 728 EP 729 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956301282 ER PT J AU Wu, O Mott, K Villien, M Copen, WA Westover, MB Edlow, BL Januzzi, JL Giacino, JT Schaefer, PW Greer, DM Rosenthal, ES AF Wu, O. Mott, K. Villien, M. Copen, W. A. Westover, M. B. Edlow, B. L. Januzzi, J. L. Giacino, J. T. Schaefer, P. W. Greer, D. M. Rosenthal, E. S. TI PRELIMINARY FINDINGS OF DIFFUSION KURTOSIS IMAGING IN COMATOSE CARDIAC ARREST PATIENTS SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Wu, O.; Mott, K.; Villien, M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Copen, W. A.; Schaefer, P. W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Westover, M. B.; Edlow, B. L.; Rosenthal, E. S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Januzzi, J. L.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Giacino, J. T.] Spaulding Rehabil Hosp, Dept Psychiat, Charlestown, MA USA. [Greer, D. M.] Yale Sch Med, Dept Neurol, New Haven, CT USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 918 BP 737 EP 738 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956301292 ER PT J AU Suh, JY Jung, H Cho, HJ Kim, YR Kim, JK Cho, G AF Suh, J. Y. Jung, H. Cho, H. J. Kim, Y. R. Kim, J. K. Cho, G. TI BLOOD VOLUME MEASUREMENTS BY DUAL T1 AND T2 MRI ACQUISITIONS WITH SINGLE T2 AGENT IN ACUTE ISCHEMIC RAT BRAIN SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Suh, J. Y.; Cho, G.] Korea Basic Sci Inst, Magnet Resonance, Cheongju, South Korea. [Jung, H.; Cho, H. J.] Ulsan Natl Inst Sci & Technol, Nanobiosci & Chem Engn, Ulsan, South Korea. [Kim, Y. R.] Massachusetts Gen Hosp, Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Kim, J. K.] Univ Ulsan, Coll Med, Asan Med Ctr, Radiol, Seoul, South Korea. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 940 BP 753 EP 754 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956301314 ER PT J AU Liu, P Chen, YI Wu, J AF Liu, P. Chen, Y. I. Wu, J. TI MONITOR GENE THERAPY IN VIVO USING TARGET-GUIDED MRI: A PRECLINICAL PLATFORM SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract C1 [Liu, P.; Chen, Y. I.] Massachusetts Gen Hosp, Radiol, Charlestown, MA USA. [Wu, J.] Florida Atlantic Univ, Biomed Sci, Boca Raton, FL 33431 USA. FU Boston Area Diabetes Endocrinology Research Center [P30DK05752114, DA029889, EB013768]; NIH [S10RR025563] FX Supported by the Boston Area Diabetes Endocrinology Research Center [P30DK05752114 (J Avruch)], DA029889 and EB013768 (PKL). TheMRI system was funded in part by NIH (S10RR025563) to the Martinos Center for Biomedical Imaging, MGH. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 SU 1 MA 989 BP 790 EP 791 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA EL9QY UT WOS:000394956301363 ER PT J AU Mul, JD la Fleur, SE AF Mul, Joram D. la Fleur, Susanne E. TI Nutritional and behavioral regulators of choice behavior SO CURRENT OPINION IN BEHAVIORAL SCIENCES LA English DT Review ID HIGH-SUGAR DIET; HIGH-FAT DIET; D-2/3 RECEPTOR AVAILABILITY; NUCLEUS-ACCUMBENS; DOPAMINE RELEASE; NEUROPEPTIDE-Y; FEEDING-BEHAVIOR; ENERGY-INTAKE; C-FOS; GALANIN AB Added sugar, often consumed in the form of sweetened beverages, is currently labeled as a big evil that increases our risk to develop obesity, cardiovascular diseases, and diabetes. Only a few decades ago, however, saturated fat received a similar negative label. Instead of singling out one of these factors we here explore how fat and sugar intake interact, thus influencing brain function and behavior. We first review current literature on how free choice during simultaneous fat and sugar consumption increases subsequent overeating and thus the risk of obesity. Next we propose neural mechanisms how simultaneous access to both fat and sugar could promote cross-sentizisation and increase total caloric intake. On the basis of our current knowledge we hypothesize that independent drinking of sugar, before or concurrent with fat intake, enhances subsequent fat-intake and total caloric intake by altering dopamine, opioid, and NPY signaling within a neural circuitry comprising of the central amygdala, the ventral tegmental area, and the nucleus accumbens. C1 [Mul, Joram D.] Harvard Med Sch, Sect Integrat Physiol & Metab, Joslin Diabet Ctr, Boston, MA USA. [la Fleur, Susanne E.] Univ Amsterdam, Acad Med Ctr, Dept Endocrinol & Metab, Amsterdam, Netherlands. RP la Fleur, SE (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Endocrinol & Metab, Amsterdam, Netherlands. EM s.e.lafleur@amc.uva.nl NR 54 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-1546 EI 2352-1554 J9 CURR OPIN BEHAV SCI JI Curr. Opin. Behav. Sci. PD JUN PY 2016 VL 9 BP 61 EP 65 DI 10.1016/j.cobeha.2016.01.009 PG 5 WC Behavioral Sciences SC Behavioral Sciences GA EM4ZV UT WOS:000395322600010 ER PT J AU Mansh, M Arron, ST AF Mansh, Matthew Arron, Sarah T. TI Indoor tanning and melanoma: are gay and bisexual men more at risk? SO MELANOMA MANAGEMENT LA English DT Editorial Material DE epidemiology; gay and bisexual; indoor tanning; melanoma; public health; sexual minority; skin cancer ID METAANALYSIS C1 [Mansh, Matthew] Calif Pacific Med Ctr, Dept Internal Med, San Francisco, CA 94115 USA. [Arron, Sarah T.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Arron, Sarah T.] San Francisco VA Med Ctr, Dermatol Serv, San Francisco, CA 94121 USA. RP Arron, ST (reprint author), Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.; Arron, ST (reprint author), San Francisco VA Med Ctr, Dermatol Serv, San Francisco, CA 94121 USA. EM sarah.arron@ucsf.edu NR 20 TC 0 Z9 0 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 2045-0885 EI 2045-0893 J9 MELANOMA MANAG JI Melanoma Manag. PD JUN PY 2016 VL 3 IS 2 BP 89 EP 92 DI 10.2217/mmt-2015-0002 PG 4 WC Oncology SC Oncology GA EK0SG UT WOS:000393636800002 ER PT J AU Ben-Ami, E Schachter, J AF Ben-Ami, Eytan Schachter, Jacob TI Adjuvant treatment for stage III melanoma in the era of targeted medicine and immunotherapy SO MELANOMA MANAGEMENT LA English DT Review DE adjuvant treatment for melanoma; anti CTLA-4; anti PD-1; MAPK pathway inhibitors ID HIGH-RISK MELANOMA; RANDOMIZED CONTROLLED-TRIAL; OPEN-LABEL; DOSE INTERFERON-ALPHA-2B; METASTATIC MELANOMA; UNTREATED MELANOMA; CUTANEOUS MELANOMA; MALIGNANT-MELANOMA; PHASE-II; PEGYLATED INTERFERON-ALPHA-2B AB The accelerated development in the treatment of metastatic melanoma, both in molecular targeted therapy and immunotherapy, is already starting to impact on adjuvant therapy in stage III melanoma. Following the approval of ipilimumab for adjuvant therapy in melanoma, clinical trials assessing other checkpoint modulators and MAPK pathway inhibitors as adjuvant treatments for melanoma are currently ongoing. As results from these trials mature in the next few years, a change in the landscape of adjuvant treatment for melanoma is expected, resulting in new challenges in treatment decisions such as optimizing patients selection through predictive and prognostic biomarkers, and management of treatment related adverse events, in particular immune related toxicities. C1 [Ben-Ami, Eytan; Schachter, Jacob] Chaim Sheba Med Ctr, Ella Lemelbaum Inst Melanoma, Div Oncol, Tel Hashomer, Israel. [Ben-Ami, Eytan] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. RP Ben-Ami, E (reprint author), Chaim Sheba Med Ctr, Ella Lemelbaum Inst Melanoma, Div Oncol, Tel Hashomer, Israel.; Ben-Ami, E (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. EM Eytan_BenAmi@dfci.harvard.edu NR 81 TC 0 Z9 0 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 2045-0885 EI 2045-0893 J9 MELANOMA MANAG JI Melanoma Manag. PD JUN PY 2016 VL 3 IS 2 BP 137 EP 147 DI 10.2217/mmt-2016-0002 PG 11 WC Oncology SC Oncology GA EK0SG UT WOS:000393636800008 ER PT J AU Young, J Chen, J Miller, M Yin, D Moon, J Alegre, ML Chong, A AF Young, J. Chen, J. Miller, M. Yin, D. Moon, J. Alegre, M. -L. Chong, A. TI Tracking of Endogenous Graft-Reactive Tregs Reveals Their Peripheral Enrichment During Transplantation Tolerance. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Young, J.; Chen, J.; Miller, M.; Yin, D.; Alegre, M. -L.; Chong, A.] Univ Chicago, Surg & Med, Chicago, IL 60637 USA. [Moon, J.] Massachusetts Gen Hosp, Immunol & Inflammatory Dis, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA 85 BP 235 EP 235 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373902085 ER PT J AU Markmann, J Guinan, E Geissler, E Cole, G Germana, S Kim, J Sawitzki, B AF Markmann, J. Guinan, E. Geissler, E. Cole, G. Germana, S. Kim, J. Sawitzki, B. TI Initial Experience with Donor Specific Tregs in Kidney Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Markmann, J.; Germana, S.; Kim, J.] Massachusetts Gen Hosp, Ctr Transplantat Sci, Boston, MA 02114 USA. [Guinan, E.; Cole, G.] Dana Farber Canc Ctr, Hematol Oncol, Boston, MA USA. [Geissler, E.] Univ Klinikum Regensburg, Surg, Regensburg, Germany. [Sawitzki, B.] Charite, Inst Med Immunol, Berlin, Germany. 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA 191 BP 271 EP 271 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373902192 ER PT J AU Wilkinson, JR Spindler, M Wood, SM Marcus, SC Weintraub, D Morley, JF Stineman, MG Duda, JE AF Wilkinson, Jayne R. Spindler, Meredith Wood, Stephanie M. Marcus, Steven C. Weintraub, Daniel Morley, James F. Stineman, Margaret G. Duda, John E. TI High patient satisfaction with telehealth in Parkinson disease A randomized controlled study SO NEUROLOGY-CLINICAL PRACTICE LA English DT Article ID RATING-SCALE; HEALTH-CARE; TELEMEDICINE; COMMUNICATION; TRIAL AB Background: Parkinson disease (PD) is a complex neurodegenerative disorder that benefits from specialty care. Telehealth is an innovative resource that can enhance access to this care within a patient-centered framework. Research suggests that telehealth can lead to increased patient satisfaction, equal or better clinical outcomes, and cost savings, but these outcomes have not been well-studied in PD. Methods: We conducted a dual active-arm 12-month randomized controlled trial to assess patient satisfaction, clinical outcomes, travel burden, and health care utilization in PD using video telehealth for follow-up care with specialty providers. Telehealth visits took place either at a facility nearer to the patient (satellite clinic arm) or in the patient's home (home arm). Each control group received usual in-person care. Patient satisfaction, assessed by quantitative questionnaires, was the primary outcome. Results: Eighty-six men were enrolled (home arm: 18 active, 18 control; satellite clinic arm: 26 active, 24 control) with a mean age of 73 years (range 42-87). There were no differences in baseline characteristics between the active group and the controls in each arm (p. 0.05). A significant difference in overall patient satisfaction was not found; however, high levels of patient satisfaction were found in all groups. Greater satisfaction for the telehealth modality was found in assessments of convenience and accessibility/distance. Clinical outcomes were similar between groups, travel burden was reduced using telehealth, and health care utilization was largely similar in both groups. Conclusions: As the need for PD subspecialty care increases, innovative patient-centered solutions to overcoming barriers to access, such as video telehealth, will be invaluable to patients and may provide high patient satisfaction. C1 [Wilkinson, Jayne R.; Spindler, Meredith; Wood, Stephanie M.; Weintraub, Daniel; Morley, James F.; Duda, John E.] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr PADRECC, Philadelphia, PA 19104 USA. [Wilkinson, Jayne R.; Spindler, Meredith; Weintraub, Daniel; Morley, James F.; Duda, John E.] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Stineman, Margaret G.] Univ Penn, Dept Phys Med Rehabil, Perelman Sch Med, Philadelphia, PA 19104 USA. [Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Wilkinson, JR (reprint author), Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr PADRECC, Philadelphia, PA 19104 USA.; Wilkinson, JR (reprint author), Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. EM jayne.wilkinson@va.gov FU VA grant - Center for the Evaluation of the Patient-Aligned Care Team (CEPACT) based out of the Philadelphia VAMC FX Funding was provided by a VA grant issued by the Center for the Evaluation of the Patient-Aligned Care Team (CEPACT) based out of the Philadelphia VAMC. NR 22 TC 3 Z9 3 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0402 EI 2163-0933 J9 NEUROL-CLIN PRACT JI Neurol.-Clin. Pract. PD JUN PY 2016 VL 6 IS 3 BP 241 EP 251 DI 10.1212/CPJ.0000000000000252 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA EJ3FY UT WOS:000393099200014 ER PT J AU Ma, R Li, T Cao, M Si, Y Wu, X Zhao, L Yao, Z Zhang, Y Fang, S Deng, R Novakovic, VA Bi, Y Kou, J Yu, B Yang, S Wang, J Zhou, J Shi, J AF Ma, R. Li, T. Cao, M. Si, Y. Wu, X. Zhao, L. Yao, Z. Zhang, Y. Fang, S. Deng, R. Novakovic, V. A. Bi, Y. Kou, J. Yu, B. Yang, S. Wang, J. Zhou, J. Shi, J. TI Extracellular DNA traps released by acute promyelocytic leukemia cells through autophagy SO CELL DEATH & DISEASE LA English DT Article ID CANCER-ASSOCIATED THROMBOSIS; TRANS-RETINOIC ACID; PHOSPHATIDYLSERINE EXPOSURE; NET FORMATION; ALPHA; RESISTANCE; DISEASE; DEATH; DIFFERENTIATION; INDUCTION AB Acute promyelocytic leukemia (APL) cells exhibit disrupted regulation of cell death and differentiation, and therefore the fate of these leukemic cells is unclear. Here, we provide the first evidence that a small percentage of APL cells undergo a novel cell death pathway by releasing extracellular DNA traps (ETs) in untreated patients. Both APL and NB4 cells stimulated with APL serum had nuclear budding of vesicles filled with chromatin that leaked to the extracellular space when nuclear and cell membranes ruptured. Using immunofluorescence, we found that NB4 cells undergoing ETosis extruded lattice-like structures with a DNA-histone backbone. During all-trans retinoic acid (ATRA)-induced cell differentiation, a subset of NB4 cells underwent ETosis at days 1 and 3 of treatment. The levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were significantly elevated at 3 days, and combined treatment with TNF-alpha and IL-6 stimulated NB4 cells to release ETs. Furthermore, inhibition of autophagy by pharmacological inhibitors or by small interfering RNA against Atg7 attenuated LC3 autophagy formation and significantly decreased ET generation. Our results identify a previously unrecognized mechanism for death in promyelocytes and suggest that ATRA may accelerate ET release through increased cytokines and autophagosome formation. Targeting this cellular death pathway in addition to conventional chemotherapy may provide new therapeutic modalities for APL. C1 [Ma, R.; Li, T.; Cao, M.; Si, Y.; Wu, X.; Zhao, L.; Yao, Z.; Zhang, Y.; Deng, R.; Zhou, J.; Shi, J.] Harbin Med Univ, Hosp 1, Dept Hematol, Harbin 150001, Peoples R China. [Ma, R.; Li, T.; Cao, M.; Si, Y.; Fang, S.; Yu, B.; Yang, S.] Minist Educ, Key Lab Myocardial Ischemia, Harbin, Heilongjiang Pr, Peoples R China. [Novakovic, V. A.] VA Boston Healthcare Syst, Brigham & Womens Hosp, Dept Res, Boston, MA USA. [Novakovic, V. A.; Shi, J.] Harvard Med Sch, Boston, MA USA. [Bi, Y.] Harbin Med Univ, Hosp 1, Dept Cardiol, Harbin, Peoples R China. [Kou, J.] Harbin Med Univ, Hosp 2, Dept Cardiol, Harbin, Peoples R China. [Wang, J.] Harbin Med Univ, Hosp 2, Dept Hematol, Harbin, Peoples R China. [Shi, J.] VA Boston Healthcare Syst, Brigham & Womens Hosp, Dept Surg, Boston, MA USA. RP Zhou, J; Shi, J (reprint author), Harbin Med Univ, Hosp 1, Dept Hematol, Harbin 150001, Peoples R China.; Yang, S; Wang, J (reprint author), Harbin Med Univ, Hosp 2, Dept Med, Harbin 150086, Peoples R China. EM shufen_yang@126.com; wang_jing_huaxy@163.com; jin_zhouxy@163.com; shi73661@gmail.com FU National Science Foundation of China [81270588, 81470301]; Graduate Innovation Fund of Harbin Medical University [YJSCX2014-02HYD] FX We thank Yanming Xue for the sample collection, and Shouchen Zhang, Yueming Chi, Lei Gao, Jiangtian Tian, Ji Li and Hulun Li for excellent technical assistance. We thank James O'Kelly (Los Angeles, CA, USA) for providing NB4 cells. This work was supported by grants from the National Science Foundation of China (81270588, 81470301) and Graduate Innovation Fund of Harbin Medical University (YJSCX2014-02HYD). NR 55 TC 2 Z9 2 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD JUN PY 2016 VL 7 AR e2283 DI 10.1038/cddis.2016.186 PG 12 WC Cell Biology SC Cell Biology GA EH5LE UT WOS:000391813800021 PM 27362801 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI Magic Tales and Fairy Tale Magic: From Ancient Egypt to the Italian Renaissance SO JOURNAL OF AMERICAN FOLKLORE LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER FOLKLORE SOC PI ARLINGTON PA 4350 NORTH FAIRFAX DR, STE 640, ARLINGTON, VA 22203 USA SN 0021-8715 EI 1535-1882 J9 J AM FOLKLORE JI J. Am. Folk. PD SUM PY 2016 VL 129 IS 513 BP 352 EP 353 PG 4 WC Folklore SC Arts & Humanities - Other Topics GA EG0ZG UT WOS:000390760500009 ER PT J AU Aoyama, A Tonsho, M Smith, RN Colvin, R Dehnadi, A Madsen, J Cosimi, A Benichou, G Kawai, T Allan, J AF Aoyama, A. Tonsho, M. Smith, R. -N. Colvin, R. Dehnadi, A. Madsen, J. Cosimi, A. Benichou, G. Kawai, T. Allan, J. TI Non-Human Primate Lung Allograft Survival Is Prolonged by IL-6 Inhibition and ATG Treatment Possibly Through Expansion of Peripheral Regulatory T Cells. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Aoyama, A.; Tonsho, M.; Smith, R. -N.; Colvin, R.; Dehnadi, A.; Madsen, J.; Cosimi, A.; Benichou, G.; Kawai, T.; Allan, J.] Massachusetts Gen Hosp, Ctr Transplantat Sci, Surg, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA 2 BP 205 EP 205 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373902002 ER PT J AU Patel, M Mohebali, J Sally, M Groat, T Vagefi, P Chang, D Malinoski, D AF Patel, M. Mohebali, J. Sally, M. Groat, T. Vagefi, P. Chang, D. Malinoski, D. TI Deceased Organ Donor Management: Does Hospital Volume Matter? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Patel, M.; Mohebali, J.; Vagefi, P.; Chang, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sally, M.; Groat, T.; Malinoski, D.] Portland VA Med Ctr, Portland, OR USA. [Sally, M.; Groat, T.; Malinoski, D.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA 22 BP 212 EP 212 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373902022 ER PT J AU Amundsen, B Sise, M Lin, M Deirawan, H Heher, E Kimball, B Markmann, J Elias, N AF Amundsen, B. Sise, M. Lin, M. Deirawan, H. Heher, E. Kimball, B. Markmann, J. Elias, N. TI Utilization of HCV-Positive Donors' Kidneys: Potential Benefits in the Era of Direct Acting Antiviral (DAA) Therapy. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Amundsen, B.; Sise, M.; Deirawan, H.; Heher, E.; Kimball, B.; Markmann, J.; Elias, N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lin, M.] Brigham & Womens Hosp, 75 Francis St, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA 75 BP 231 EP 231 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373902075 ER PT J AU Cravedi, P Purroy, C Madsen, J Fairchild, R Tanaka, T Baldwin, W Alessandrini, A Heeger, P AF Cravedi, P. Purroy, C. Madsen, J. Fairchild, R. Tanaka, T. Baldwin, W., III Alessandrini, A. Heeger, P. TI Erythropoietin (EPO) Mediates Spontaneous Kidney Transplant Tolerance in Mice. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Cravedi, P.; Purroy, C.; Heeger, P.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Madsen, J.; Alessandrini, A.] Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Madsen, J.; Alessandrini, A.] Harvard Med Sch, Boston, MA USA. [Fairchild, R.; Tanaka, T.; Baldwin, W., III] Cleveland Clin Fdn, Dept Immunol 3, 9500 Euclid Ave, Cleveland, OH 44195 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA 83 BP 234 EP 234 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373902083 ER PT J AU AlFadil, S Kim, MJ Lozano, MI Oh, B Lee, W Brandacher, G Serworld, T Raimondi, G AF AlFadil, S. Kim, M. -J. Lozano, M. Iglesias Oh, B. Lee, W. Brandacher, G. Serworld, T. Raimondi, G. TI Engineering a "Hybrid Thymus" to Promote Transplant Tolerance. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [AlFadil, S.; Lozano, M. Iglesias; Oh, B.; Lee, W.; Brandacher, G.; Raimondi, G.] Johns Hopkins Med Inst, Plast & Recnstruct Surg, Baltimore, MD 21205 USA. [Kim, M. -J.; Serworld, T.] Joslin Diabet Ctr, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA 88 BP 235 EP 236 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373902088 ER PT J AU Chatterjee, D Moore, C Gao, B Clerkin, K See, S Shaked, D Rogers, K Nunez, S Veras, Y Addonizio, L Givertz, M Naka, Y Mancini, D Vasilescu, R Marboe, C Restaino, S Madsen, J Zorn, E AF Chatterjee, D. Moore, C. Gao, B. Clerkin, K. See, S. Shaked, D. Rogers, K. Nunez, S. Veras, Y. Addonizio, L. Givertz, M. Naka, Y. Mancini, D. Vasilescu, R. Marboe, C. Restaino, S. Madsen, J. Zorn, E. TI Prevalence of Polyreactive Innate-Like B Cells Among GraftInfiltrating B Cells in Human Cardiac Allograft Vasculopathy SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Chatterjee, D.; Clerkin, K.; See, S.; Shaked, D.; Rogers, K.; Nunez, S.; Veras, Y.; Addonizio, L.; Naka, Y.; Mancini, D.; Restaino, S.; Zorn, E.] Columbia Univ, Med Ctr, Med, New York, NY USA. [Moore, C.; Madsen, J.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Gao, B.] Jilin Univ, Hosp 1, Changchun, Peoples R China. [Givertz, M.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Vasilescu, R.; Marboe, C.] Columbia Univ, Med Ctr, Pathol & Cell Biol, New York, NY 10027 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA 170 BP 263 EP 263 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373902170 ER PT J AU Amundsen, B Deirawan, H Kim, J Markmann, J AF Amundsen, B. Deirawan, H. Kim, J. Markmann, J. TI Expansion of Regulatory B-Cells and Their Potential Role in Transplantation Tolerance SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Amundsen, B.; Deirawan, H.; Kim, J.; Markmann, J.] 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA 181 BP 267 EP 268 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373902181 ER PT J AU Kawai, T Chen, YB Sykes, M Benedict, C Tolkoff-Rubin, N Day, B McAfee, S Ballen, K David, S Spitzer, T AF Kawai, T. Chen, Y. -B. Sykes, M. Benedict, C. Tolkoff-Rubin, N. Day, B. McAfee, S. Ballen, K. David, S. Spitzer, T. TI HLA Identical or Haploidentical Combined Kidney and Bone Marrow Transplantation for Multiple Myeloma with End-Stage Renal Failure SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Kawai, T.; Chen, Y. -B.; Benedict, C.; Tolkoff-Rubin, N.; Day, B.; McAfee, S.; David, S.; Spitzer, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sykes, M.] Columbia Univ, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA 187 BP 270 EP 270 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373902188 ER PT J AU Savage, T Dewolf, S Obradovic, A Lau, S Zuber, J Turka, L Shen, Y Sykes, M AF Savage, T. Dewolf, S. Obradovic, A. Lau, S. Zuber, J. Turka, L. Shen, Y. Sykes, M. TI Clonal Expansion of Donor-Specific Tregs Following Combined Kidney and Bone Marrow Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Savage, T.; Dewolf, S.; Obradovic, A.; Lau, S.; Zuber, J.; Shen, Y.; Sykes, M.] Columbia Univ, New York, NY USA. [Turka, L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Turka, L.] Immune Tolerance Network, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA 189 BP 270 EP 271 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373902190 ER PT J AU Oh, N Yang, C Tonsho, M Ndishabandi, D Russell, P Colvin, R Madsen, J Alessandrini, A AF Oh, N. Yang, C. Tonsho, M. Ndishabandi, D. Russell, P. Colvin, R. Madsen, J. Alessandrini, A. TI Distinct Phenotype and Function of Plasmacytoid Dendritic Cells from Kidney Allografts in Tolerant Recipients. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Oh, N.; Yang, C.; Tonsho, M.; Ndishabandi, D.; Russell, P.; Colvin, R.; Madsen, J.; Alessandrini, A.] Massachusetts Gen Hosp, Ctr Transplantat Sci, Boston, MA 02114 USA. [Oh, N.; Yang, C.; Tonsho, M.; Ndishabandi, D.; Russell, P.; Madsen, J.; Alessandrini, A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Yang, C.; Ndishabandi, D.; Colvin, R.] Massachusetts Gen Hosp, Dept Pathol, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA 205 BP 275 EP 275 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373902206 ER PT J AU Charlton, M Yoshida, E Bouliere, M Flamm, S Muir, A Fried, M Terrault, N Arterburn, S Yun, C Pang, P Osinusi, A Spellman, J Natha, M Brainard, D McHutchison, J Manns, M Afdhal, N AF Charlton, M. Yoshida, E. Bouliere, M. Flamm, S. Muir, A. Fried, M. Terrault, N. Arterburn, S. Yun, C. Pang, P. Osinusi, A. Spellman, J. Natha, M. Brainard, D. McHutchison, J. Manns, M. Afdhal, N. TI High Efficacy of Ledipasvir/Sofosbuvir with Ribavirin in HCV Genotype-1 Infected Patients with Decompensated Liver Disease: Analysis by MELD Score from the SOLAR-1 and SOLAR-2 Trials. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Charlton, M.] Intermt Med Ctr, Salt Lake City, UT USA. [Yoshida, E.] Vancouver Gen Hosp, Vancouver, BC, Canada. [Bouliere, M.] Hop St Joseph, Marseilles, France. [Flamm, S.] Northwestern Univ, Chicago, IL 60611 USA. [Muir, A.] Duke Univ, Durham, NC 27706 USA. [Fried, M.] Univ N Carolina, Chapel Hill, NC USA. [Terrault, N.] UCSF, Sf, CA USA. [Arterburn, S.; Yun, C.; Pang, P.; Osinusi, A.; Spellman, J.; Natha, M.; Brainard, D.; McHutchison, J.] Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA. [Manns, M.] Hannover Med Sch, Hannover, Germany. [Afdhal, N.] BIDMC, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA 265 BP 297 EP 297 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373902266 ER PT J AU Kim, J Stott, R Deirawan, H Kojima, L Washburn, L Zhao, G Yeh, H Markmann, J AF Kim, J. Stott, R. Deirawan, H. Kojima, L. Washburn, L. Zhao, G. Yeh, H. Markmann, J. TI Ageing as a Barrier to Transplant Tolerance. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Kim, J.; Stott, R.; Deirawan, H.; Kojima, L.; Washburn, L.; Zhao, G.; Yeh, H.; Markmann, J.] Harvard Med, Massachusetts Gen Hosp, Surg Transplant, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA 293 BP 307 EP 307 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373902294 ER PT J AU Kotton, C AF Kotton, C. TI Assessing Return of CMV Specific Cellular Immunity Using the T-SPOT. CMV Soon After Kidney Transplant with Thymoglobulin. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Kotton, C.] Massachusetts Gen Hosp, Infect Dis, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA 308 BP 311 EP 311 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373902309 ER PT J AU Schuetz, C Lee, K Kojima, L Washburn, L Liu, L Liu, WH Kim, J Markmann, J AF Schuetz, C. Lee, K. Kojima, L. Washburn, L. Liu, L. Liu, W. -H. Kim, J. Markmann, J. TI NK Cells Are Required in B-Cell Dependent, Antibody Mediated Islet Transplant Tolerance. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Schuetz, C.; Lee, K.; Kojima, L.; Washburn, L.; Liu, L.; Liu, W. -H.; Kim, J.; Markmann, J.] Massachusetts Gen Hosp, Dept Surg, Transplant Surg Div, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA 372 BP 334 EP 334 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373902377 ER PT J AU Deirawan, H Kojima, L Washburn, L Markmann, J Kim, J AF Deirawan, H. Kojima, L. Washburn, L. Markmann, J. Kim, J. TI TGFb in Regulatory B Cells-Dependent Tolerance. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Deirawan, H.; Kojima, L.; Washburn, L.; Markmann, J.; Kim, J.] Massachusetts Gen Hosp, Surg, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA 376 BP 335 EP 336 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373902381 ER PT J AU Rosales, I DeFazio, M Foreman, R Sachs, D Cetrulo, C Leonard, D Colvin, R AF Rosales, I. DeFazio, M. Foreman, R. Sachs, D. Cetrulo, C. Leonard, D. Colvin, R. TI Systematic Pathological Component Scores for Skin-Containing Vascularized Composite Allografts. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Rosales, I.; Foreman, R.; Colvin, R.] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. [DeFazio, M.; Sachs, D.; Cetrulo, C.; Leonard, D.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Plast & Reconstruct Surg, Boston, MA 02114 USA. [Leonard, D.] Countess Chester Hosp, Plast & Reconstruct Surg, Chester, Cheshire, England. 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA 381 BP 337 EP 337 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373902386 ER PT J AU Mihali, A Karreci, E Kurdi, A Riella, L Kawano, Y Fan, H Singh, P Ghobrial, I Nathan, C Lin, G Azzi, J AF Mihali, A. Karreci, E. Kurdi, A. Riella, L. Kawano, Y. Fan, H. Singh, P. Ghobrial, I. Nathan, C. Lin, G. Azzi, J. TI Designing and Synthesizing a Novel Highly Selective Immunoproteasome Inhibitor That Promotes Long Term Heart Allograft Acceptance While Reducing Plasma Cells and Donor Specific Antibodies. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Mihali, A.; Karreci, E.; Riella, L.; Azzi, J.] Harvard Med Sch, Transplantat Res Ctr, Boston, MA USA. [Fan, H.; Singh, P.; Nathan, C.; Lin, G.] Weill Cornell Med, Dept Microbiol & Immunol, New York, NY USA. [Kurdi, A.; Kawano, Y.; Ghobrial, I.] Dana Farber Canc Inst, Dept Med Oncol, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA 469 BP 367 EP 367 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373902474 ER PT J AU Tonsho, M Benichou, G Yu, R Boskovic, S Colvin, R Farkash, E Smith, RN Allan, J Cosimi, A Kawai, T Madsen, J AF Tonsho, M. Benichou, G. Yu, R. Boskovic, S. Colvin, R. Farkash, E. Smith, R. -N. Allan, J. Cosimi, A. Kawai, T. Madsen, J. TI Delayed Induction of Mixed Chimerism Permits Kidney-Induced Cardiac Allograft Tolerance to be Applied to Recipients of Cadaveric Organs. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Tonsho, M.; Benichou, G.; Yu, R.; Boskovic, S.; Colvin, R.; Allan, J.; Cosimi, A.; Kawai, T.; Madsen, J.] Massachusetts Gen Hosp, Dept Surg, Ctr Transplantat Sci, Boston, MA 02114 USA. [Colvin, R.; Farkash, E.; Smith, R. -N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kawai, T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Allan, J.; Madsen, J.] Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA 478 BP 370 EP 370 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373902483 ER PT J AU Braza, M Lameijer, M Perez-Medina, C Reiner, T Nahrendorf, M Fayad, Z Duivenvoorden, R Ochando, J Mulder, W AF Braza, M. Lameijer, M. Perez-Medina, C. Reiner, T. Nahrendorf, M. Fayad, Z. Duivenvoorden, R. Ochando, J. Mulder, W. TI Rapamycin Nanotherapy Delays Heart Transplant Rejection. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Braza, M.; Lameijer, M.; Perez-Medina, C.; Fayad, Z.; Duivenvoorden, R.; Mulder, W.] Icahn Sch Med Mt Sinai, Translat & Mol Imaging Inst, New York, NY 10029 USA. [Ochando, J.] Icahn Sch Med Mt Sinai, Oncol Sci, New York, NY 10029 USA. [Reiner, T.] Mem Sloan Kettering Canc Ctr, Radiol, 1275 York Ave, New York, NY 10021 USA. [Nahrendorf, M.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Nahrendorf, M.] Harvard Med Sch, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA 538 BP 391 EP 392 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373902543 ER PT J AU Adam, B Rosales, I Oura, T Smith, R Cosimi, A Kawai, T Colvin, R Mengel, M AF Adam, B. Rosales, I. Oura, T. Smith, R. Cosimi, A. Kawai, T. Colvin, R. Mengel, M. TI Molecular Diagnosis of Antibody-Mediated Rejection in Routine Formalin-Fixed Paraffin-Embedded Nonhuman Primate Renal Allograft Biopsies SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Adam, B.; Mengel, M.] Univ Alberta, Edmonton, AB, Canada. [Rosales, I.; Oura, T.; Smith, R.; Cosimi, A.; Kawai, T.; Colvin, R.] Harvard Med Sch, Boston, MA USA. [Rosales, I.; Oura, T.; Smith, R.; Cosimi, A.; Kawai, T.; Colvin, R.; Mengel, M.] 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA A16 BP 409 EP 410 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373903016 ER PT J AU Hotta, K Oura, T Cosimi, B Kawai, T AF Hotta, K. Oura, T. Cosimi, B. Kawai, T. TI The Property of Modulatory T Cells Generated by Mixed Lymphocyte Culture with CD154 Blockade SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Hotta, K.; Oura, T.; Cosimi, B.; Kawai, T.] Massachusetts Gen Hosp, Ctr Transplantat Sci, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA A27 BP 413 EP 413 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373903027 ER PT J AU Sremac, M Saraya, A Clemente, O Penson, M Chavan, S Chronos, N Schuetz, C Lei, J Markmann, J Brauns, T Poznansky, M AF Sremac, M. Saraya, A. Clemente, O. Penson, M. Chavan, S. Chronos, N. Schuetz, C. Lei, J. Markmann, J. Brauns, T. Poznansky, M. TI CXCL12 as Innovative Immune Isolating Chemokine for Microencapsulated Allo and Xeno-Transplantation in NHPs SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Sremac, M.; Saraya, A.; Clemente, O.; Penson, M.; Brauns, T.; Poznansky, M.] Massachusetts Gen Hosp, Infect Dis VIC, Boston, MA 02114 USA. [Schuetz, C.; Lei, J.; Markmann, J.] Massachusetts Gen Hosp, Div Transplantat, Boston, MA 02114 USA. [Chavan, S.; Chronos, N.] VICapsys Inc, Athens, GA 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA A28 BP 413 EP 413 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373903028 ER PT J AU Yu, R Tonsho, M Spencer, P Bernard-Stoecklin, S Benichou, G Madsen, J AF Yu, R. Tonsho, M. Spencer, P. Bernard-Stoecklin, S. Benichou, G. Madsen, J. TI Characterization of T Regulatory Type 1 (Tr1) Cells in Naive and Transplanted Non-Human Primates SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Yu, R.; Tonsho, M.; Spencer, P.; Bernard-Stoecklin, S.; Benichou, G.; Madsen, J.] Massachusetts Gen Hosp, Ctr Transplantat Sci, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA A32 BP 414 EP 414 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373903032 ER PT J AU Schol, I Drijkoningen, T Choy, G Liu, R Tanrikut, C Holzer, P Ko, D Cetrulo, C AF Schol, I. Drijkoningen, T. Choy, G. Liu, R. Tanrikut, C. Holzer, P. Ko, D. Cetrulo, C. TI Planning Genitourinary Vascularized Composite Allotransplantation: A Pre-Operative Imaging Protocol SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Schol, I.; Drijkoningen, T.; Choy, G.; Liu, R.; Tanrikut, C.; Holzer, P.; Ko, D.; Cetrulo, C.] 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA A87 BP 430 EP 430 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373903086 ER PT J AU Xu, Y Navarro-Alvarez, N Dong, J Markmann, J Yeh, H AF Xu, Y. Navarro-Alvarez, N. Dong, J. Markmann, J. Yeh, H. TI Cytokine Storm in Acute Post-Hepatectmy Phase Associates with Liver Injury and Impaired Liver Regeneration. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Xu, Y.; Navarro-Alvarez, N.; Markmann, J.; Yeh, H.] Massachusetts Gen Hosp, Transplantat Div, Boston, MA 02114 USA. [Xu, Y.; Dong, J.] Chinese Peoples Liberat Army Gen Hosp, Dept Hepatobiliary Surg, Beijing, Peoples R China. 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA A203 BP 469 EP 469 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373903201 ER PT J AU Bassi, R Niewczas, M Biancone, L Bussolino, S Lin, A Chandraker, A Fiorina, P AF Bassi, R. Niewczas, M. Biancone, L. Bussolino, S. Lin, A. Chandraker, A. Fiorina, P. TI Metabolomic Profiling of Individuals with Failing Kidney Allograft. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Bassi, R.; Fiorina, P.] Boston Childrens Hosp, Nephrol, Boston, MA USA. [Bassi, R.; Fiorina, P.] IRCCS San Raffaele Hosp, Transplant Med, Milan, Italy. [Niewczas, M.] Joslin Diabet Ctr, Genet & Epidemiol, Boston, MA 02215 USA. [Lin, A.] Brigham & Womens Hosp, Radiol, 75 Francis St, Boston, MA 02115 USA. [Biancone, L.; Bussolino, S.] San Giovanni Battista Hosp, Nephrol & Transplantat, Turin, Italy. [Chandraker, A.] Brigham & Womens Hosp, Transplantat Res Ctr, 75 Francis St, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA A229 BP 478 EP 479 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373903227 ER PT J AU Babiker-Mohamed, M Marino, J Crosby, P Benichou, G AF Babiker-Mohamed, M. Marino, J. Crosby, P. Benichou, G. TI Activation of Alloreactive T Cells by Allogeneic Exosomes and Cells Cross-Dressed with Allogeneic MHC Molecules. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 Massachusetts Gen Hosp, Dept Surg, Ctr Transplantat Sci, Boston, MA 02114 USA. Harvard Med Sch, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA B3 BP 502 EP 502 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373903305 ER PT J AU Marino, J Paster, J Crosby, P Uehara, M Mordecai, S Abdi, R Tocco, G Benichou, G AF Marino, J. Paster, J. Crosby, P. Uehara, M. Mordecai, S. Abdi, R. Tocco, G. Benichou, G. TI Direct Alloimmunity Is Driven by Recipient APCs Displaying Donor MHC Molecules. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Marino, J.; Paster, J.; Crosby, P.; Mordecai, S.; Tocco, G.; Benichou, G.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Transplantat Sci, Surg Dept, Boston, MA USA. [Uehara, M.; Abdi, R.] Brigham & Womens Hosp, Dept Med, Div Renal, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA B13 BP 505 EP 505 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373903315 ER PT J AU Yang, C Farkash, E Ndishabandi, D White, R Jiang, B Aljabban, I Russell, P Madsen, J Colvin, R Alessandrini, A AF Yang, C. Farkash, E. Ndishabandi, D. White, R. Jiang, B. Aljabban, I. Russell, P. Madsen, J. Colvin, R. Alessandrini, A. TI Treg-Rich Organized Lymphoid Structures (TOLS) in Spontaneously Accepted Mouse Kidney Allografts SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Yang, C.; Ndishabandi, D.; White, R.; Jiang, B.; Aljabban, I.; Russell, P.; Madsen, J.; Colvin, R.; Alessandrini, A.] Massachusetts Gen Hosp, Dept Pathol, Dept Surg, Ctr Transplantat Sci, Boston, MA 02114 USA. [Farkash, E.] Univ Michigan, Sch Med, Ann Arbor, MI 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA B34 BP 511 EP 512 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373903336 ER PT J AU Adler, J Markmann, J Chang, D Yeh, H AF Adler, J. Markmann, J. Chang, D. Yeh, H. TI Neighborhood Socioeconomic Characteristics Influence Access to Kidney Transplantation Independently of Individual Socioeconomic Status SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Adler, J.; Markmann, J.; Chang, D.; Yeh, H.] Massachusetts Gen Hosp, Surg, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA B49 BP 515 EP 516 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373903351 ER PT J AU Bababekov, Y Fong, Z Adler, J Yeh, H Chang, D Pomposelli, J AF Bababekov, Y. Fong, Z. Adler, J. Yeh, H. Chang, D. Pomposelli, J. TI Assessment of Transplant Health Literacy of Liver Transplant Candidates and Their Caregivers SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Bababekov, Y.; Fong, Z.; Adler, J.; Yeh, H.; Chang, D.] Harvard Med Sch, Massachusetts Gen Hosp, Surg, Boston, MA USA. [Fong, Z.; Chang, D.] Harvard Med Sch, Massachusetts Gen Hosp, Codman Ctr Clin Effectivness Surg, Boston, MA USA. [Pomposelli, J.] Lahey Hosp & Med Ctr, Transplantat, Burlington, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA B57 BP 518 EP 518 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373903359 ER PT J AU Li, Y Verkouw, K Tabtabai, S Barrios, R Gill, R Koo, J Marboe, C Rodriguez, E Tan, C De Marco, T Estep, J Hanna, M Maurer, M Patel, J Selby, V Semigran, M Stone, J AF Li, Y. Verkouw, K. Tabtabai, S. Barrios, R. Gill, R. Koo, J. Marboe, C. Rodriguez, E. Tan, C. De Marco, T. Estep, J. Hanna, M. Maurer, M. Patel, J. Selby, V. Semigran, M. Stone, J. TI Using Gastrointestinal Biopsy to Predict Outcome in Patients Evaluated for Cardiac Transplantation for Amyloidosis: A Report from the International Consortium on Cardiac Amyloidosis Transplantation (iCCAT). SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Li, Y.; Verkouw, K.; Tabtabai, S.; Semigran, M.; Stone, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Barrios, R.; Estep, J.] Methodist Hosp, 6535 Fannin, Houston, TX 77030 USA. [Gill, R.; De Marco, T.; Selby, V.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Koo, J.; Patel, J.] Cedars Sinai Heart Inst, Los Angeles, CA USA. [Marboe, C.; Maurer, M.] Columbia Univ, Med Ctr, New York, NY USA. [Rodriguez, E.; Tan, C.; Hanna, M.] Cleveland Clin, Cleveland, OH 44106 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA B166 BP 555 EP 556 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373904051 ER PT J AU Pouch, S Lease, E Bogdanovich, T Ho, D Miller, R Estabrook, M Babu, T Kotton, C Shaver, C Thomas, L Aslam, S McCarty, T Garcia-Diaz, J Doucette, K Kirkby, S van Duin, D AF Pouch, S. Lease, E. Bogdanovich, T. Ho, D. Miller, R. Estabrook, M. Babu, T. Kotton, C. Shaver, C. Thomas, L. Aslam, S. McCarty, T. Garcia-Diaz, J. Doucette, K. Kirkby, S. van Duin, D. TI Susceptibility Patterns of Pre-Transplant Pseudomonas and Post-Lung Transplant Outcomes in Patients with Cystic Fibrosis. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Pouch, S.] Ohio State Univ, Columbus, OH 43210 USA. [Lease, E.] Univ Washington, Seattle, WA 98195 USA. [Bogdanovich, T.] Univ Pittsburgh, Pittsburgh, PA USA. [Ho, D.] Stanford Univ, Stanford, CA 94305 USA. [Miller, R.] Univ Iowa, Iowa City, IA USA. [Estabrook, M.] Washington Univ, St Louis, MO USA. [Babu, T.; Kotton, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shaver, C.; Thomas, L.] Vanderbilt Univ, Nashville, TN 37235 USA. [Aslam, S.] Univ Calif San Diego, San Diego, CA 92103 USA. [McCarty, T.] Univ Alabama, Birmingham, AB, Canada. [Garcia-Diaz, J.] Ochsner Clin Fdn, New Orleans, LA USA. [Doucette, K.] Univ Alberta, Edmonton, AB, Canada. [Kirkby, S.] Nationwide Childrens Hosp, Columbus, OH USA. [van Duin, D.] Univ N Carolina, Chapel Hill, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA B283 BP 593 EP 593 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373904166 ER PT J AU Michel, S Madariaga, M LaMuraglia, G Colvin, R Farkash, E Allan, J Sachs, D Yamada, K Madsen, J AF Michel, S. Madariaga, M. LaMuraglia, G., II Colvin, R. Farkash, E. Allan, J. Sachs, D. Yamada, K. Madsen, J. TI The Effects of Brain Death and Ischemia on Tolerance Induction Are Organ-Specific. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Michel, S.; Madariaga, M.; LaMuraglia, G., II; Allan, J.; Sachs, D.; Yamada, K.; Madsen, J.] Massachusetts Gen Hosp, Ctr Transplantat Sci, Boston, MA 02114 USA. [Michel, S.; Madariaga, M.; LaMuraglia, G., II; Colvin, R.; Farkash, E.; Allan, J.; Sachs, D.; Yamada, K.; Madsen, J.] Harvard Med Sch, Boston, MA USA. [Michel, S.] Ludwig Maximilians Univ Munchen, Dept Cardiac Surg, Munich, Germany. [Colvin, R.; Farkash, E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Allan, J.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. [Madsen, J.] Massachusetts Gen Hosp, Div Cardiac Surg, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA C132 BP 644 EP 644 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373904320 ER PT J AU Zhong, Z Ko, D Wang, Y Ye, Q AF Zhong, Z. Ko, D. Wang, Y. Ye, Q. TI Hypothermic Machine Perfusion Ameliorates Vasospasm and Edema of Podocytes and Renal Tubular Epithelial Cells Through Upregulating Expression of Kruppel-Like Factors 2 SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Zhong, Z.; Wang, Y.; Ye, Q.] Wuhan Univ, Inst Hepatobiliary Dis, Zhongnan Hosp, Wuhan, Hubei, Peoples R China. [Ko, D.] Harvard Med Sch, Dept Urol, Massachusetts Gen 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA C180 BP 659 EP 659 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373904368 ER PT J AU Huh, K Tonsho, M Spencer, P Paster, J Wu, X Hanekamp, I Kawai, T Smith, R Cosimi, A Dehnadi, A Benichou, G Colvin, R Madsen, J AF Huh, K. Tonsho, M. Spencer, P. Paster, J. Wu, X. Hanekamp, I. Kawai, T. Smith, R. Cosimi, A. Dehnadi, A. Benichou, G. Colvin, R. Madsen, J. TI Delaying the Induction of Mixed Chimerism Until Two Months After NHP Heart and Kidney Cotransplantation Results in Long Term Survival. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Huh, K.; Tonsho, M.; Spencer, P.; Paster, J.; Wu, X.; Hanekamp, I.; Kawai, T.; Cosimi, A.; Dehnadi, A.; Benichou, G.; Colvin, R.; Madsen, J.] Massachusetts Gen Hosp, Dept Surg, Ctr Transplantat Sci, Boston, MA 02114 USA. [Smith, R.; Colvin, R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kawai, T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Madsen, J.] Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA D62 BP 718 EP 718 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373905142 ER PT J AU Hotta, K Oura, T Crisalli, K Sachs, D Cosim, B Kawai, T AF Hotta, K. Oura, T. Crisalli, K. Sachs, D. Cosim, B. Kawai, T. TI Immune Tolerance Monitoring in Renal Allograft Tolerance Induced by Transient Mixed Chimerism in Nonhuman Primates and Humans. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Hotta, K.; Oura, T.; Crisalli, K.; Sachs, D.; Cosim, B.; Kawai, T.] Massachusetts Gen Hosp, Ctr Transplantat Sci, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA D88 BP 726 EP 726 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373905168 ER PT J AU Oura, T Hotta, K Crisalli, K Cosimi, B Kawai, T AF Oura, T. Hotta, K. Crisalli, K. Cosimi, B. Kawai, T. TI IL-10 Expression of In Vitro Activated B Cells as A Biomarker for B Cell Tolerance. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Oura, T.; Hotta, K.; Crisalli, K.; Cosimi, B.; Kawai, T.] Massachusetts Gen Hosp, Ctr Transplantat Sci, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA D89 BP 726 EP 727 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373905169 ER PT J AU Bruinsma, B Avruch, J Sridharan, G Weeder, P Karimian, N Markmann, J Uygun, K Yeh, H AF Bruinsma, B. Avruch, J. Sridharan, G. Weeder, P. Karimian, N. Markmann, J. Uygun, K. Yeh, H. TI Metabolic Recovery and Ex Vivo Simulation of Early Liver Reperfusion. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Bruinsma, B.; Sridharan, G.; Weeder, P.; Karimian, N.; Uygun, K.] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [Avruch, J.; Markmann, J.; Yeh, H.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA D120 BP 737 EP 737 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373905200 ER PT J AU Adler, J Bababekov, Y Markmann, J Chang, D Yeh, H AF Adler, J. Bababekov, Y. Markmann, J. Chang, D. Yeh, H. TI Pediatric Kidney Transplantation and Mortality: Distance to Transplant Center Matters. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Adler, J.; Bababekov, Y.; Markmann, J.; Chang, D.; Yeh, H.] Massachusetts Gen Hosp, Surg, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA D158 BP 750 EP 750 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373905238 ER PT J AU Aljabban, I Jiang, B Yang, C Ndishabandi, D White, R Russell, P Madsen, J Colvin, R Alessandrini, A AF Aljabban, I. Jiang, B. Yang, C. Ndishabandi, D. White, R. Russell, P. Madsen, J. Colvin, R. Alessandrini, A. TI Accepted Mouse Kidney Allografts Are Characterized by Widespread Nitrosylation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY JUN 11-15, 2016 CL Boston, MA C1 [Aljabban, I.; Jiang, B.; Yang, C.; Ndishabandi, D.; White, R.; Russell, P.; Madsen, J.; Colvin, R.; Alessandrini, A.] Massachusetts Gen Hosp, Dept Pathol, Ctr Transplantat Sci, Dept Surg, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 SU 3 SI SI MA D303 BP 795 EP 795 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DW1AB UT WOS:000383373905383 ER PT J AU Kopacz, MS Feldstein, BD Asekoff, CA Kaprow, MS Smith-Coggins, R Connery, AL AF Kopacz, Marek S. Feldstein, Bruce D. Asekoff, Cecille Allman Kaprow, Maurice S. Smith-Coggins, Rebecca Connery, April L. TI A preliminary study examining chaplains' support for veterans at the end of life SO INTERNATIONAL JOURNAL OF PALLIATIVE NURSING LA English DT Article DE Chaplains; Veterans; End of Life AB This descriptive study examines the involvement of professional chaplains in addressing loss of dignity, inconsequential life or not having a legacy, fear of burdensomeness, and fear of pain in veterans at the end of life. A convenience sample of Jewish chaplains responded to an online survey gauging their involvement in these areas. Results are presented descriptively. Most respondents stated either rarely (<= 1 x month) or sometimes (>= 1 x month) encountering veterans with end-of-life issues. Respondents reported varying degrees of involvement in supporting veterans at the end of life with respect to the aforementioned areas. As research into the end-of-life care needs of veterans continues to develop, recognising chaplains as a source of both spiritual and psychosocial support can serve as an opportunity for better meeting the needs of this population. C1 [Kopacz, Marek S.; Connery, April L.] US Dept Vet Affairs, Canandaigua, NY 14424 USA. [Feldstein, Bruce D.] Stanford Med, Stanford, CA USA. [Asekoff, Cecille Allman; Kaprow, Maurice S.] Neshama Assoc Jewish Chaplains, Paramus, NJ USA. [Smith-Coggins, Rebecca] Stanford Univ, Emergency Med, Stanford, CA 94305 USA. RP Kopacz, MS (reprint author), US Dept Vet Affairs, Canandaigua, NY 14424 USA. EM marek.kopacz@va.gov NR 13 TC 1 Z9 1 U1 0 U2 0 PU MARK ALLEN GROUP PI LONDON PA ST JUDES CHURCH, DULWICH RD, LONDON, SE24 0PB, ENGLAND SN 1357-6321 J9 INT J PALLIAT NURS JI Int. J. Palliat. Nurs. PD JUN PY 2016 VL 22 IS 6 BP 300 EP 302 PG 3 WC Nursing SC Nursing GA EE1CQ UT WOS:000389318800007 PM 27349849 ER PT J AU Stange, JP Kleiman, EM Sylvia, LG Magalhaes, PVD Berk, M Nierenberg, AA Deckersbach, T AF Stange, Jonathan P. Kleiman, Evan M. Sylvia, Louisa G. Magalhaes, Pedro Vieira da Silva Berk, Michael Nierenberg, Andrew A. Deckersbach, Thilo TI SPECIFIC MOOD SYMPTOMS CONFER RISK FOR SUBSEQUENT SUICIDAL IDEATION IN BIPOLAR DISORDER WITH AND WITHOUT SUICIDE ATTEMPT HISTORY: MULTI-WAVE DATA FROM STEP-BD SO DEPRESSION AND ANXIETY LA English DT Article DE bipolar disorder; depression; mood disorders; suicide/self-harm; cognition ID ECOLOGICAL MOMENTARY ASSESSMENT; TREATMENT ENHANCEMENT PROGRAM; PREVALENCE; DEPRESSION; BEHAVIOR; SLEEP AB Background: Little is known about specific mood symptoms that may confer risk for suicidal ideation (SI) among patients with bipolar disorder (BD). We evaluated prospectively whether particular symptoms of depression and mania precede the onset or worsening of SI, among adults with or without a history of a suicide attempt. Methods: We examined prospective data from a large (N = 2,741) cohort of patients participating in the Systematic Treatment Enhancement Program for BD (STEP-BD). We evaluated history of suicide attempts at baseline, and symptoms of depression and mania at baseline and follow-up visits. Hierarchical linear modeling tested whether specific mood symptoms predicted subsequent levels of SI, and whether the strength of the associations differed based on suicide attempt history, after accounting for the influence of other mood symptoms and current SI. Results: Beyond overall current depression and mania symptom severity, baseline SI, and illness characteristics, several mood symptoms, including guilt, reduced self-esteem, psychomotor retardation and agitation, increases in appetite, and distractibility predicted more severe levels of subsequent SI. Problems with concentration, distraction, sleep loss and decreased need for sleep predicted subsequent SI more strongly among individuals with a suicide attempt history. Conclusions: Several specific mood symptoms may confer risk for the onset or worsening of SI among treatment-seeking patients with BD. Individuals with a previous suicide attempt may be at greater risk in part due to greater reactivity to certain mood symptoms in the form of SI. However, overall, effect sizes were small, suggesting the need to identify additional proximal predictors of SI. Depression and Anxiety 33:464-472, 2016. (C) 2016 Wiley Periodicals, Inc. C1 [Stange, Jonathan P.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. [Kleiman, Evan M.] Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. [Sylvia, Louisa G.; Nierenberg, Andrew A.; Deckersbach, Thilo] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sylvia, Louisa G.; Nierenberg, Andrew A.; Deckersbach, Thilo] Harvard Med Sch, Boston, MA USA. [Magalhaes, Pedro Vieira da Silva] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Natl Inst Translat Med, Porto Alegre, RS, Brazil. [Berk, Michael] Deakin Univ, Barwon Hlth, Sch Med, IMPACT Strateg Res Ctr, Geelong, Vic, Australia. [Berk, Michael] Univ Melbourne, Dept Psychiat, Natl Ctr Excellence Youth Mental Hlth, Orygen, Parkville, Vic, Australia. [Berk, Michael] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic, Australia. RP Deckersbach, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bipolar Clin, 50 Staniford St,5th Floor, Boston, MA 02114 USA.; Deckersbach, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Res Program, 50 Staniford St,5th Floor, Boston, MA 02114 USA. EM tdeckersbach@partners.org FU National Institute of Mental Health [N01MH80001] FX Contract grant sponsor: National Institute of Mental Health (Gary Sachs); Contract grant number: N01MH80001. NR 43 TC 1 Z9 1 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JUN PY 2016 VL 33 IS 6 BP 464 EP 472 DI 10.1002/da.22464 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA DW5SW UT WOS:000383708200002 PM 26756163 ER PT J AU Beristianos, MH Maguen, S Neylan, TC Byers, AL AF Beristianos, Matthew H. Maguen, Shira Neylan, Thomas C. Byers, Amy L. TI TRAUMA EXPOSURE AND RISK OF SUICIDAL IDEATION AMONG ETHNICALLY DIVERSE ADULTS SO DEPRESSION AND ANXIETY LA English DT Article DE trauma exposure; suicidal ideation; race/ethnicity; posttraumatic stress disorder; major depressive disorder; child maltreatment ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL COMORBIDITY SURVEY; SURVEY REPLICATION; PREVALENCE; EVENTS; SAMPLE; CHILD; EPIDEMIOLOGY; PREDICTORS; COMMUNITY AB Background: Little is known about the association between trauma exposure and suicidal ideation across racial/ethnic groups. Our study aim was to determine the association between trauma exposure and suicidal ideation in a nationally representative ethnically diverse sample of adults. Methods: This study included 14,866 White, Hispanic, Black, and Asian participants 18 years and older involved in the Collaborate Psychiatric Epidemiology Surveys (2001-2003), comprised of three nationally representative studies (NCS-R, NSAL, and NLAAS). Lifetime history of suicidal ideation as assessed in the World Health Organization'sWorld Mental Health Survey Initiative version of the Composite International Diagnostic Interview (WMH-CIDI). Results: Of the 81% respondents who reported being exposed to trauma as assessed in the WMH-CIDI, 12.1% endorsed lifetime suicidal ideation. Additionally, of the 19% who did not report trauma, 1.1% endorsed lifetime suicidal ideation. Fully adjusted, multivariable logistic regression models revealed two traumas consistently associated with significantly higher odds for suicidal ideation across all four racial groups examined: Assaultive/interpersonal violence and child maltreatment. Asians, in particular, had the highest likelihood for suicidal ideation in both trauma categories, with a near threefold increased odds for assaultive/interpersonal violence exposure (OR: 2.56; 95% CI: 1.71-3.83) and nearly ninefold increased odds for child maltreatment exposure (OR: 8.43; 95% CI: 4.91-14.49). Discussion: : Suicidal ideation in racially/ethnically diverse American adults is strongly associated with assaultive/interpersonal violence and child maltreatment, independent of PTSD, MDD, and substance use. These findings highlight the need for monitoring of suicidal behavior following assaultive/interpersonal trauma and child maltreatment, regardless of the presence of a psychiatric disorder. Depression and Anxiety 33:495-501, 2016. (C) 2016 Wiley Periodicals, Inc. C1 [Beristianos, Matthew H.; Maguen, Shira; Neylan, Thomas C.; Byers, Amy L.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Beristianos, Matthew H.; Maguen, Shira; Neylan, Thomas C.; Byers, Amy L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Beristianos, Matthew H.] Alliant Int Univ, San Francisco, CA USA. RP Beristianos, MH (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco VA Med Ctr, 4150 Clement St 116H, San Francisco, CA 94121 USA. EM matthew.beristianos@va.gov FU National Institutes of Health; National Institute on Minority Health and Health Disparities; Northern California Institute for Research and Education; San Francisco Veterans Affairs Medical Center; National Institute of Mental Health [U01-MH60220, U01-MH57716, U01-MH062209, U01-MH62207]; National Institute of Drug Abuse [R01-DA12058-05]; Office of Behavioral and Social Sciences Research at the National Institute of Health; University of Michigan; Office of Behavioral and Social Sciences Research at the National Institutes of Health; Substance Abuse and Mental Health Services Agency; Latino Research Program Project [P01-MH059876] FX Contract grant sponsor: National Institutes of Health, National Institute on Minority Health and Health Disparities (to A.L.B); contract grant sponsor: Northern California Institute for Research and Education and with resources from the San Francisco Veterans Affairs Medical Center (to M.H.B.); contract grant sponsor: National Institute of Mental Health; contract grant number: U01-MH60220; contract grant sponsor: National Institute of Drug Abuse; contract grant number: R01-DA12058-05; contract grant sponsor: National Institute of Mental Health; contract grant number: U01-MH57716; contract grant sponsor: Office of Behavioral and Social Sciences Research at the National Institute of Health, and the University of Michigan; contract grant sponsor: National Institute of Mental Health; contract grant number: U01-MH062209 and U01-MH62207; contract grant sponsor: Office of Behavioral and Social Sciences Research at the National Institutes of Health, the Substance Abuse and Mental Health Services Agency, and the Latino Research Program Project; contract grant number: P01-MH059876. NR 31 TC 1 Z9 1 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JUN PY 2016 VL 33 IS 6 BP 495 EP 501 DI 10.1002/da.22485 PG 7 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA DW5SW UT WOS:000383708200005 PM 26992150 ER PT J AU Betz, ME Miller, M Barber, C Beaty, B Miller, I Camargo, CA Boudreaux, ED AF Betz, Marian E. Miller, Matthew Barber, Catherine Beaty, Brenda Miller, Ivan Camargo, Carlos A., Jr. Boudreaux, Edwin D. TI LETHAL MEANS ACCESS AND ASSESSMENT AMONG SUICIDAL EMERGENCY DEPARTMENT PATIENTS SO DEPRESSION AND ANXIETY LA English DT Article DE suicide/self-harm; treatment; assessment/diagnosis; clinical trials; depression; epidemiology ID UNITED-STATES; MEANS RESTRICTION; YOUTH SUICIDE; PREVENTION; RISK; POPULATION; PROVIDERS; FIREARMS; SAFETY; INTERVENTIONS AB Background: Reducing access to lethal means (especially firearms) might prevent suicide, but counseling of at-risk individuals about this strategy may not be routine. Among emergency department (ED) patients with suicidal ideation or attempts (SI/SA), we sought to describe home firearm access and examine ED provider assessment of access to lethal means. Methods: This secondary analysis used data from the Emergency Department Safety Assessment and Follow-up Evaluation, a three-phase, eight-center study of adult ED patients with SI/SA (2010-2013). Research staff surveyed participants about suicide-related factors (including home firearms) and later reviewed the ED chart (including documented assessment of lethal means access). Results: Among 1,358 patients with SI/SA, 11% (95% CI: 10-13%) reported >= 1 firearm at home; rates varied across sites (range: 6-26%) but not over time. On chart review, 50% (95% CI: 47-52%) of patients had documentation of lethal means access assessment. Frequency of documented assessment increased over study phases (40-60%, P <.001) but was not associated with state firearm ownership rates. Among the 337 (25%, 95% CI: 23-27%) patients discharged to home, 55% (95% CI: 49-60%) had no documentation of lethal means assessment; of these, 13% (95% CI: 8-19%; n = 24) actually had >= 1 firearm at home. Among all those reporting >= 1 home firearm to study staff, only half (50%, 95% CI: 42-59%) had provider documentation of assessment of lethal means access. Conclusions: Among these ED patients with SI/SA, many did not have documented assessment of home access to lethal means, including patients who were discharged home and had >= 1 firearm at home. Depression and Anxiety 33: 502-511, 2016. (C) 2016 Wiley Periodicals, Inc. C1 [Betz, Marian E.] Univ Colorado, Sch Med, Dept Emergency Med, 12401 E 17th Ave B-215, Aurora, CO 80045 USA. [Miller, Matthew; Barber, Catherine] Harvard Sch Publ Hlth, Harvard Injury Control Res Ctr, Boston, MA USA. [Beaty, Brenda] Univ Colorado Anschutz Med Campus, Adult & Child Ctr Hlth Outcomes Res & Delivery Sc, Aurora, CO USA. [Miller, Ivan] Butler Hosp, Providence, RI 02906 USA. [Camargo, Carlos A., Jr.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA 01655 USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. RP Betz, ME (reprint author), Univ Colorado, Sch Med, Dept Emergency Med, 12401 E 17th Ave B-215, Aurora, CO 80045 USA. EM marian.betz@ucdenver.edu FU National Institute of Mental Health, Paul Beeson Career Development Award [U01MH088278]; National Institute on Aging; AFAR; John A. Hartford Foundation; Atlantic Philanthropies [K23AG043123]; Joyce Foundation [14-36094] FX Contract grant sponsor: National Institute of Mental Health, Paul Beeson Career Development Award; Contract grant number: U01MH088278; Contract grant sponsor: National Institute on Aging; AFAR; John A. Hartford Foundation; and Atlantic Philanthropies; Contract grant number: K23AG043123; Contract grant sponsor: Joyce Foundation; Contract grant number: 14-36094. NR 35 TC 2 Z9 2 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JUN PY 2016 VL 33 IS 6 BP 502 EP 511 DI 10.1002/da.22486 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA DW5SW UT WOS:000383708200006 PM 26989850 ER PT J AU Bryan, CJ Clemans, TA Hernandez, AM Mintz, J Peterson, AL Yarvis, JS Resick, PA AF Bryan, Craig J. Clemans, Tracy A. Hernandez, Ann Marie Mintz, Jim Peterson, Alan L. Yarvis, Jeffrey S. Resick, Patricia A. CA The Strong Star Consortium TI EVALUATING POTENTIAL IATROGENIC SUICIDE RISK IN TRAUMA-FOCUSED GROUP COGNITIVE BEHAVIORAL THERAPY FOR THE TREATMENT OF PTSD IN ACTIVE DUTY MILITARY PERSONNEL SO DEPRESSION AND ANXIETY LA English DT Article DE suicidal ideation; PTSD; depression; adverse effects; psychotherapy ID POSTTRAUMATIC-STRESS-DISORDER; SERVICEMEMBERS ARMY STARRS; IV MENTAL-DISORDERS; PROCESSING THERAPY; IDEATION; PREVALENCE; RESILIENCE; VETERANS; EXPOSURE; SOLDIERS AB Objective: To determine whether group cognitive processing therapy-cognitive only version (CPT-C) is associated with iatrogenic suicide risk in a sample of active duty US Army personnel diagnosed with posttraumatic stress disorder (PTSD). Possible iatrogenic effects considered include the incidence and severity of suicide ideation, worsening of preexisting suicide ideation, incidence of new-onset suicide ideation, and incidence of suicide attempts among soldiers receiving group CPT-C. Comparison with group present-centered therapy (PCT) was made to contextualize findings. Method: One hundred eight soldiers (100 men, eight women) diagnosed with PTSD were randomized to receive either group CPT-C or group PCT. PTSD diagnosis was confirmed via structured clinician interview. Suicide ideation, depression severity, and PTSD severity were assessed at pretreatment, weekly during treatment, and 2 weeks, 6 months, and 12 months posttreatment. Results: Rates of suicide ideation significantly decreased across both treatments. Among soldiers with pretreatment suicide ideation, severity of suicide ideation significantly decreased across both treatments and was maintained for up to 12 months posttreatment. Exacerbation of preexisting suicide ideation was uncommon in both treatments. New-onset suicide ideation was rare and similar across both treatments (<16%). There were no suicide attempts during treatment or follow-up in either group. Change in depression symptoms predicted change in suicide risk. Conclusions: Suicide-related outcomes were similar across both treatments and primarily associated with comorbid depression. Suicide-related outcomes in group CPT-C were rare and comparable to patterns observed in an active, nontrauma-focused therapy, even among soldiers who entered treatment with suicide ideation. Clinical Trials.gov Identifier: NCT01286415, https://clinicaltrials.gov/ct2/show/NCT01286415. Depression and Anxiety 33:549-557, 2016. (C) 2015 Wiley Periodicals, Inc. C1 [Bryan, Craig J.] Natl Ctr Vet Studies, 260 S Cent Campus Dr,Room 205, Salt Lake City, UT 84112 USA. [Bryan, Craig J.] Univ Utah, Dept Psychol, Salt Lake City, UT 84112 USA. [Clemans, Tracy A.] Natl Ctr Vet Studies, Salt Lake City, UT USA. [Hernandez, Ann Marie; Mintz, Jim; Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Peterson, Alan L.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Peterson, Alan L.] Univ Texas San Antonio, Dept Psychol, San Antonio, TX USA. [Yarvis, Jeffrey S.] Carl R Darnall Army Med Ctr, Dept Behav Hlth, Ft Hood, TX USA. [Resick, Patricia A.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. RP Bryan, CJ (reprint author), Natl Ctr Vet Studies, 260 S Cent Campus Dr,Room 205, Salt Lake City, UT 84112 USA. EM craig.bryan@utah.edu FU US Department of Defense; Military Suicide Research Consortium (MSRC) FX Contract grant sponsor: US Department of Defense; Contract grant sponsor: Military Suicide Research Consortium (MSRC). NR 39 TC 4 Z9 4 U1 5 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JUN PY 2016 VL 33 IS 6 BP 549 EP 557 DI 10.1002/da.22456 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA DW5SW UT WOS:000383708200011 PM 26636426 ER PT J AU Rosenberg, SM Ruddy, KJ Tamimi, RM Gelber, S Schapira, L Come, S Borges, VF Larsen, B Garber, JE Partridge, AH AF Rosenberg, Shoshana M. Ruddy, Kathryn J. Tamimi, Rulla M. Gelber, Shari Schapira, Lidia Come, Steven Borges, Virginia F. Larsen, Bryce Garber, Judy E. Partridge, Ann H. TI BRCA1 and BRCA2 Mutation Testing in Young Women With Breast Cancer SO JAMA ONCOLOGY LA English DT Article ID CONTRALATERAL PROPHYLACTIC MASTECTOMY; IMPACT; PERCEPTIONS; DIAGNOSIS; KNOWLEDGE AB IMPORTANCE BRCA testing is recommended for young women diagnosed as having breast cancer, but little is known about decisions surrounding testing and how results may influence treatment decisions in young patients. OBJECTIVES To describe the use of BRCA testing and to evaluate how concerns about genetic risk and use of genetic information affect subsequent treatment decisions in young women with breast cancer. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional analysis of data collected following the opening of the study to accrual from October 10, 2006, through December 31, 2014, as part of the Helping Ourselves, Helping Others: Young Women's Breast Cancer Study, an ongoing prospective cohort study. Study participants included 897 women aged 40 years and younger at breast cancer diagnosis from 11 academic and community medical centers. MAIN OUTCOMES AND MEASURES Frequency and trends in the use of BRCA testing and how genetic information is used to make treatment decisions among women who test positive vs negative for a BRCA mutation. RESULTS A total of 780 (87.0%) of 897 women reported BRCA testing by 1 year after breast cancer diagnosis (mean age at diagnosis, 35.3 vs 36.9 years for untested women; P < .001), with the frequency of testing increasing among women diagnosed from August 1, 2006, through December 31, 2013. Of 39 women who were diagnosed as having breast cancer in 2006, 30 (76.9%) reported testing. In 2007, a slightly lower percentage of women (87 of 124 [70.2%]) reported testing; however, the proportion tested increased each subsequent year, with 141 (96.6%) of 146 and 123 (95.3%) of 129 women diagnosed as having breast cancer in 2012 and 2013, respectively, reporting BRCA testing (P <.001). Among untested women, 37 (31.6%) of 117 did not report discussion of the possibility that they might have a mutation with a physician and/or genetic counselor, and 43 (36.8%) of 117 were thinking of testing in the future. A total of 248 (29.8%) of 831 women said that knowledge or concern about genetic risk influenced treatment decisions; among these women, 76 (86.4%) of 88 mutation carriers and 82 (51.2%) of 160 noncarriers chose bilateral mastectomy (P < .001). Fewer women reported that systemic treatment decisions were influenced by genetic risk concern. CONCLUSIONS AND RELEVANCE Rates of BRCA1 and BRCA2 mutation testing are increasing in young women with breast cancer. Given that knowledge and concern about genetic risk influence surgical decisions and may affect systemic therapy trial eligibility, all young women with breast cancer should be counseled and offered genetic testing, consistent with the National Comprehensive Cancer Network guidelines. C1 [Rosenberg, Shoshana M.; Larsen, Bryce; Garber, Judy E.; Partridge, Ann H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ruddy, Kathryn J.] Mayo Clin, Deparment Oncol, Rochester, MN USA. [Tamimi, Rulla M.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Gelber, Shari] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Schapira, Lidia] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Come, Steven] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Borges, Virginia F.] Univ Colorado, Ctr Canc, Div Med Oncol, Denver, CO 80202 USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM ahpartridge@partners.org FU Susan G. Komen for the Cure [SAC100008]; National Institutes of Health [R25 CA057711] FX This study was funded by grant SAC100008 from the Susan G. Komen for the Cure (Dr Partridge), grant R25 CA057711 from the National Institutes of Health (Dr Rosenberg), and The Pink Agenda (Dr Rosenberg). NR 21 TC 7 Z9 7 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD JUN PY 2016 VL 2 IS 6 BP 730 EP 736 DI 10.1001/jamaoncol.2015.5941 PG 7 WC Oncology SC Oncology GA DW5RE UT WOS:000383703600007 PM 26867710 ER PT J AU Cao, Y Nishihara, R Wu, KN Wang, ML Ogino, S Willett, WC Spiegelman, D Fuchs, CS Giovannucci, EL Chan, AT AF Cao, Yin Nishihara, Reiko Wu, Kana Wang, Molin Ogino, Shuji Willett, Walter C. Spiegelman, Donna Fuchs, Charles S. Giovannucci, Edward L. Chan, Andrew T. TI Population-wide Impact of Long-term Use of Aspirin and the Risk for Cancer SO JAMA ONCOLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RANDOMIZED CONTROLLED-TRIALS; NATIONAL DEATH INDEX; COLORECTAL-CANCER; PROSTATE-CANCER; FOLLOW-UP; HEALTH-PROFESSIONALS; PROSPECTIVE COHORT; CHRONIC DISEASE; BREAST-CANCER AB IMPORTANCE The US Preventive Services Task Force recently recommended the use of aspirin to prevent colorectal cancer and cardiovascular disease among many US adults. However, the association of aspirin use with the risk for other cancer types and the potential population-wide effect of aspirin use on cancer, particularly within the context of screening, remain uncertain. OBJECTIVES To examine the potential benefits of aspirin use for overall and subtype-specific cancer prevention at a range of doses and durations of use and to estimate the absolute benefit of aspirin in the context of screening. DESIGN, SETTING, AND PARTICIPANTS Two large US prospective cohort studies, the Nurses' Health Study (1980-2010) and Health Professionals Follow-up Study (1986-2012), followed up 135 965 health care professionals (88 084 women and 47 881 men, respectively) who reported on aspirin use biennially. The women were aged 30 to 55 years at enrollment in 1976; the men, aged 40 to 75 years in 1986. Final follow-up was completed on June 30, 2012, for the Nurses' Health Study cohort and January 31, 2010, for the Health Professionals Follow-up Study cohort, and data were accessed from September 15, 2014, to December 17, 2015. MAIN OUTCOMES AND MEASURES Relative risks (RRs) for incident cancers and population-attributable risk (PAR). RESULTS Among the 88 084 women and 47 881 men who underwent follow-up for as long as 32 years, 20 414 cancers among women and 7571 cancers among men were documented. Compared with nonregular use, regular aspirin use was associated with a lower risk for overall cancer (RR, 0.97; 95% CI, 0.94-0.99), which was primarily owing to a lower incidence of gastrointestinal tract cancers (RR, 0.85; 95% CI, 0.80-0.91), especially colorectal cancers (RR, 0.81; 95% CI, 0.75-0.88). The benefit of aspirin on gastrointestinal tract cancers appeared evident with the use of at least 0.5 to 1.5 standard aspirin tablets per week; the minimum duration of regular use associated with a lower risk was 6 years. Among individuals older than 50 years, regular aspirin use could prevent 33 colorectal cancers per 100 000 person-years (PAR, 17.0%) among those who had not undergone a lower endoscopy and 18 colorectal cancers per 100 000 person-years (PAR, 8.5%) among those who had. Regular aspirin use was not associated with the risk for breast, advanced prostate, or lung cancer. CONCLUSIONS AND RELEVANCE Long-term aspirin use was associated with a modest but significantly reduced risk for overall cancer, especially gastrointestinal tract tumors. Regular aspirin use may prevent a substantial proportion of colorectal cancers and complement the benefits of screening. C1 [Cao, Yin; Nishihara, Reiko; Wu, Kana; Willett, Walter C.; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Cao, Yin; Chan, Andrew T.] Massachusetts Gen Hosp, Harvard Med Sch, Clin & Translat Epidemiol Unit, Boston, MA USA. [Cao, Yin; Chan, Andrew T.] Massachusetts Gen Hosp, Harvard Med Sch, Div Gastroenterol, Boston, MA USA. [Nishihara, Reiko; Wang, Molin; Ogino, Shuji; Willett, Walter C.; Spiegelman, Donna; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Nishihara, Reiko; Wang, Molin] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Nishihara, Reiko; Ogino, Shuji; Fuchs, Charles S.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Ogino, Shuji] Brigham & Womens Hosp, Harvard Med Sch, Dept Pathol, Boston, MA USA. [Willett, Walter C.; Fuchs, Charles S.; Giovannucci, Edward L.; Chan, Andrew T.] Brigham & Womens Hosp, Harvard Med Sch, Channing Div Network Med, Boston, MA USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, 55 Fruit St, Boston, MA 02114 USA. EM achan@mgh.harvard.edu FU National Institutes of Health [P01 CA87969, UM1 CA186107, UM1 CA167552, R01 CA137178, R01 CA151993, R35 CA197735, K24 DK098311, K07 CA190673] FX This study was supported by grants P01 CA87969, UM1 CA186107, UM1 CA167552, R01 CA137178, R01 CA151993, R35 CA197735, K24 DK098311, and K07 CA190673 from the National Institutes of Health. NR 49 TC 19 Z9 22 U1 4 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD JUN PY 2016 VL 2 IS 6 BP 762 EP 769 DI 10.1001/jamaoncol.2015.6396 PG 8 WC Oncology SC Oncology GA DW5RE UT WOS:000383703600012 PM 26940135 ER PT J AU Oxnard, GR Wilcox, KH Gonen, M Polotsky, M Hirsch, BR Schwartz, LH AF Oxnard, Geoffrey R. Wilcox, Katharine H. Gonen, Mithat Polotsky, Mikhael Hirsch, Bradford R. Schwartz, Lawrence H. TI Response Rate as a Regulatory End Point in Single-Arm Studies of Advanced Solid Tumors SO JAMA ONCOLOGY LA English DT Article ID CELL LUNG-CANCER; BREAKTHROUGH THERAPY DESIGNATION; II CLINICAL-TRIALS; DRUG DEVELOPMENT; MELANOMA; PROGRESSION; INHIBITION; RESISTANCE; ONCOLOGY; PROGRAMS AB IMPORTANCE Objective response rate (ORR) is an increasingly important end point for accelerated development of highly active anticancer therapies, yet its relationship to regulatory approval is not well characterized. OBJECTIVE To identify circumstances in which a high ORR is associated with regulatory approval, and therefore might be an appropriate end point for definitive single-arm studies of anticancer therapies. DATA SOURCE A database of all oncology clinical trials registered at clinicaltrials. gov between October 1, 2007, and September 30, 2010. STUDY SELECTION Trials of palliative systemic therapies for 4 measurable solid tumor types, limited to those with trial arms of at least 20 patients reporting ORR per Response Evaluation Criteria in Solid Tumors (RECIST). DATA EXTRACTION AND SYNTHESIS A systematic search was used to identify the reported ORR for each eligible treatment arm that had been presented publicly. MAIN OUTCOMES AND MEASURES For each treatment regimen, defined as a single-agent or unique combination of agents for 1 cancer type, the mean ORR and the maximum ORR statistically exceeded were calculated, and their association with regulatory approval was studied. A regimen was considered approved for a specific cancer type if it had received regulatory approval in any country for treatment of advanced cancer of that type. RESULTS From 1800 trials, 874 eligible trial arms in 578 eligible trials were identified; 542 arms had ORR data available for 294 regimens. Maximum ORR and mean ORR were significantly associated with regulatory approval (tau = 0.27, P <.001; tau = 0.12, P = .01); this relationship was stronger for single-agent therapies (tau = 0.49; tau = 0.41) than for combination regimens (tau = 0.28; tau = 0.17). Evaluation of ORR thresholds between 20% and 60% as potential trial end points demonstrated that ORR statistically exceeding 30% with a single agent had 98% specificity and 89% positive predictive value for identifying regimens achieving regulatory approval. CONCLUSIONS AND RELEVANCE For single-agent regimens, high ORR was associated with regulatory approval; this relationship was less strong for combination regimens. Our data suggest that high ORR (eg, statistically exceeding an ORR of 30%) is an appropriate end point for single-arm trials aiming to demonstrate breakthrough activity of a single-agent anticancer therapy. C1 [Oxnard, Geoffrey R.; Wilcox, Katharine H.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Gonen, Mithat] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY USA. [Polotsky, Mikhael; Schwartz, Lawrence H.] Columbia Univ Coll Phys & Surg, Dept Radiol, New York Presbyterian Hosp, New York, NY 10032 USA. [Hirsch, Bradford R.] Duke Canc Inst, Duke Canc Care Res Program, Dallas, TX USA. RP Schwartz, LH (reprint author), Columbia Univ Coll Phys & Surg, Dept Radiol, 180 Ft Washington Ave,Ste 320, New York, NY 10032 USA. EM lschwartz@columbia.edu FU Stading-Younger Cancer Research Foundation; National Cancer Institute of the National Institutes of Health [U01-CA140207] FX This research was supported in part by the Stading-Younger Cancer Research Foundation and the National Cancer Institute of the National Institutes of Health (U01-CA140207). NR 28 TC 2 Z9 2 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD JUN PY 2016 VL 2 IS 6 BP 772 EP 779 DI 10.1001/jamaoncol.2015.6315 PG 8 WC Oncology SC Oncology GA DW5RE UT WOS:000383703600014 PM 26914340 ER PT J AU Sanders, JL Arnold, AM Hirsch, CH Thielke, SM Kim, D Mukamal, KJ Kizer, JR Ix, JH Kaplan, RC Kritchevsky, SB Newman, AB AF Sanders, Jason L. Arnold, Alice M. Hirsch, Calvin H. Thielke, Stephen M. Kim, Dae Mukamal, Kenneth J. Kizer, Jorge R. Ix, Joachim H. Kaplan, Robert C. Kritchevsky, Stephen B. Newman, Anne B. TI Effects of Disease Burden and Functional Adaptation on Morbidity and Mortality on Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE adaptation; function; morbidity; frailty; longevity ID CARDIOVASCULAR HEALTH; ASSOCIATION; DEPRESSION; DISABILITY; LIFE AB OBJECTIVES: To ascertain whether older adults with extensive disease but relative vigor (adapters) shorten the period at the end of life in which they live with morbidity (compress morbidity). DESIGN: Prospective, community-based cohort study in four U.S. cities. SETTING: Cardiovascular Health Study. PARTICIPANTS: Individuals aged 65 and older. MEASUREMENTS: Participants were categorized into three groups according to extent of disease (assessed non-invasively), vigor, and frailty (expected agers (n = 3,528, extent of disease similar to vigor and frailty-reference group), adapters (n = 882, higher disease but vigorous), and prematurely frail (n = 855, lower disease but frail)) and compared according to years of able life (YAL), years of self-reported healthy life (YHL), and mortality using multivariable regression and survival analysis. RESULTS: After adjustment, adapters had 0.97 (95% confidence interval (CI) = 0.60-1.33) more YAL and 0.54 (95% CI = 0.19-0.90) more YHL than expected agers, and those who were prematurely frail had -0.99 (95% CI = -1.36 to -0.62) fewer YAL and -0.53 (95% CI = -0.89 to -0.17) fewer YHL than expected agers. Adapters had 0.9 more and prematurely frail had 1.5 fewer years of total life than expected agers (P<.001). Adapters spent 55% of their remaining life able and healthy, those who were prematurely frail spent 37%, and of expected agers spent 47% (P<.001). CONCLUSION: Despite similar levels of disease burden, older adults who were more vigorous appeared to compress morbidity and live longer. Older adults with higher frailty lengthened morbidity and had greater mortality. Adaptive factors may compress morbidity and decrease mortality. C1 [Sanders, Jason L.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA. [Arnold, Alice M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Hirsch, Calvin H.] Univ Calif Davis, Dept Med, Sacramento, CA 95817 USA. [Thielke, Stephen M.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Thielke, Stephen M.] Puget Sound VA Med Ctr, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Kim, Dae; Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Kizer, Jorge R.] Yeshiva Univ, Dept Med, Bronx, NY USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Kaplan, Robert C.] Yeshiva Univ, Dept Epidemiol & Populat Hlth, Bronx, NY USA. [Kritchevsky, Stephen B.] Wake Forest Sch Med, Dept Med, Winston Salem, NC USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP Sanders, JL (reprint author), BWH Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. EM jsanders2@partners.org FU National Heart, Lung, and Blood Institute [HHSN 268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC 85082, N01HC85083, N01HC85086, U01HL080295]; National Institute on Aging [R01AG023629] FX This research was supported by Contracts HHSN 268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC 85082, N01HC85083, and N01HC85086 and Grant U01HL080295 from the National Heart, Lung, and Blood Institute with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by R01AG023629 from the National Institute on Aging. A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. NR 23 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUN PY 2016 VL 64 IS 6 BP 1242 EP 1249 DI 10.1111/jgs.14163 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DW3MY UT WOS:000383546900011 PM 27321602 ER PT J AU Cho, J Copeland, LA Stock, EM Zeber, JE Restrepo, MI MacCarthy, AA Ory, MG Smith, PA Stevens, AB AF Cho, Jinmyoung Copeland, Laurel A. Stock, Eileen M. Zeber, John E. Restrepo, Marcos I. MacCarthy, Andrea A. Ory, Marcia G. Smith, Paul A. Stevens, Alan B. TI Protective and Risk Factors for 5-Year Survival in the Oldest Veterans: Data from the Veterans Health Administration SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE health services; oldest; survival; veterans ID POSTTRAUMATIC-STRESS-DISORDER; MILITARY SERVICE; BLOOD-PRESSURE; MORTALITY; CARE; ADULTS; AFFAIRS; IMPACT; LIFE; SCHIZOPHRENIA AB OBJECTIVES: To characterize physical and mental diseases and use of healthcare services and identify factors associated with mortality in the oldest individuals using the Veterans Health Administration (VHA). DESIGN: Retrospective study with 5-year survival follow-up. SETTING: VHA, system-wide. PARTICIPANTS: Veterans using the VHA aged 80 and older as of October 2008 (N = 721,588: n = 665,249 aged 80-89, n = 56,118 aged 90-99, n = 221 aged 100-115). MEASUREMENTS: Demographic characteristics, physical and mental diseases, healthcare services, and 5-year survival were measured. RESULTS: Accelerated failure time models identified protective and risk factors associated with mortality according to age group. During 5 years of follow-up, 44% of participants died (survival rate: 59% aged 80-89, 32% aged 90-99, 15% aged >= 100). In the multivariable model, protective effects for veterans aged 80-99 were female sex, minority race or ethnicity, being married, having certain physical and mental diagnoses (hypertension, cataract, dyslipidemia, posttraumatic stress disorder, bipolar disorder), having urgent care visits, having invasive surgery, and having few (1-3) prescriptions. Risk factors were lower VHA priority status, physical and mental conditions (diabetes mellitus, anemia, congestive heart failure, dementia, anxiety, depression, smoking, substance abuse disorder), hospital admission, and nursing home care. For those aged 100 and older, being married, smoking, hospital admission, nursing home care, invasive surgery, and prescription use were significant risk factors; only emergency department (ED) use was protective. CONCLUSION: Although the data are limited to VHA care (thus missing Medicare services), this study shows that many veterans served by the VHA live to advanced old age despite multiple chronic conditions. Further study is needed to determine whether a comprehensive, coordinated care system like VHA is associated with greater longevity for very old persons. C1 [Cho, Jinmyoung; Copeland, Laurel A.; Stock, Eileen M.; Zeber, John E.; Smith, Paul A.; Stevens, Alan B.] Baylor Scott & White Hlth, MS 01-501,2401 S 31st St, Temple, TX 76508 USA. [Cho, Jinmyoung; Copeland, Laurel A.; Stock, Eileen M.; Zeber, John E.; Ory, Marcia G.; Stevens, Alan B.] Texas A&M Hlth Sci Ctr, College Stn, TX USA. [Copeland, Laurel A.; Stock, Eileen M.; Zeber, John E.] Cent Texas Vet Hlth Care Syst, Temple, TX USA. [Restrepo, Marcos I.] Univ Texas San Antonio, Hlth Sci Ctr, San Antonio, TX USA. [Restrepo, Marcos I.; MacCarthy, Andrea A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Cho, J (reprint author), Baylor Scott & White Hlth, MS 01-501,2401 S 31st St, Temple, TX 76508 USA. EM jinmyoung.cho@bswhealth.org OI Copeland, Laurel/0000-0002-9478-0209 FU VHA [HX-09-335]; National Institute of Mental Health; Scott White Research; VA Office of Rural Health; Henry M. Jackson Foundation for the Advancement of Military Medicine; Wounded Warrior Project; Walmart Foundation; May & Stanley Smith Charitable Trust; Robert R. McCormick Foundation; Onward Veterans and Schultz Family Foundation; Bob Woodruff Foundation; Phil Marge Odeen; Rumsfeld Foundation; National Heart, Lung, and Blood Institute [K23HL096054] FX Laurel Copeland: unpaid Governing Board member representing Baylor Scott & White in the Health Care Systems Research Network (formerly HMO Research Network); grant funding from the VHA including HX-09-335, National Institute of Mental Health, Scott & White Research, VA Office of Rural Health, the Henry M. Jackson Foundation for the Advancement of Military Medicine (with Wounded Warrior Project, Walmart Foundation, May & Stanley Smith Charitable Trust, Robert R. McCormick Foundation, Onward Veterans and Schultz Family Foundation, Bob Woodruff Foundation, Phil & Marge Odeen, and the Rumsfeld Foundation). John Zeber: Health Services Research and Development Service merit grant on infectious disease (PI), Mental Health Research Network (coinvestigator), Astra-Zeneca drug safety study (PI, pending); board (unpaid): Academy health behavioral interest group advisory board, World Journal of Psychiatry editorial board. Marcos Restrepo's time is partially protected by Award K23HL096054 from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute; National Institutes of Health; or Department of Veterans Affairs. NR 49 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUN PY 2016 VL 64 IS 6 BP 1250 EP 1257 DI 10.1111/jgs.14161 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DW3MY UT WOS:000383546900012 PM 27321603 ER PT J AU Cagle, JG McClymont, KM Thai, JN Smith, AK AF Cagle, John G. McClymont, Keelan M. Thai, Julie N. Smith, Alexander K. TI "If You Don't Know, All of a Sudden, They're Gone": Caregiver Perspectives About Prognostic Communication for Disabled Elderly Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE informal caregivers; communication; prognosis; life expectancy; uncertainty; hope; older adults ID LATE-LIFE DISABILITY; OF-LIFE; DISCUSSING PROGNOSIS; OLDER-ADULTS; FAMILY CAREGIVERS; END; PREFERENCES; PERCEPTIONS; DEATH; CARE AB OBJECTIVES: To describe preferences and experiences of caregivers of disabled older adults regarding being included in patient-clinician discussions about life expectancy. DESIGN: Qualitative interview study. SETTING: Caregivers were recruited from a Program of All-Inclusive Care for the Elderly (PACE), caregiver support groups and an advertisement on a nationwide caregiver advocacy group website. PARTICIPANTS: Active and bereaved caregivers whose primary language was either English or Cantonese who had provided care within the last 5 years to a disabled adult aged 65 and older (N = 42, 79% female, 60% white, average age 54). MEASUREMENTS: Semistructured telephone interviews were conducted with caregivers who were asked about experiences and preferences related to clinician communication about life expectancy, including preferences for and attitudes toward being included in discussions about life expectancy, how such information should be delivered, and how clinicians should address concerns about uncertainty and hope. Responses were analyzed qualitatively using constant comparison until thematic saturation was reached. RESULTS: Twenty-six percent of caregivers had been involved in a conversation with a clinician about life expectancy, even though 79% expressed a preference to have such a discussion. According to caregivers, clinician concerns about taking away hope or the uncertainty of prognostic information should not deter them from bringing up the topic of life expectancy. Thematic analysis suggested several approaches that may facilitate prognosis communication: establishing a relationship with the care-giver and care recipient; delivering the prognosis in clear, plain language; and responding to emotion with empathy. CONCLUSION: Caregivers reported a preference for being included in conversations about a care recipient's life expectancy. C1 [Cagle, John G.] Univ Maryland, Baltimore, MD 21201 USA. [McClymont, Keelan M.; Thai, Julie N.; Smith, Alexander K.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [McClymont, Keelan M.; Smith, Alexander K.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Cagle, JG (reprint author), 525 West Redwood St,3W13, Baltimore, MD 21201 USA. EM jcagle@ssw.umaryland.edu FU National Institute on Aging (NIA) [5T32AG000212]; National Palliative Care Research Center; NIA [K23 040772]; American Federation for Aging Research FX Dr. Cagle's efforts were supported by the National Institute on Aging (NIA) (5T32AG000212) and a Junior Faculty Career Development Award from the National Palliative Care Research Center. Dr. Smith was supported by the NIA (K23 040772) and the American Federation for Aging Research. NR 27 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUN PY 2016 VL 64 IS 6 BP 1299 EP 1306 DI 10.1111/jgs.14137 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DW3MY UT WOS:000383546900019 PM 27321609 ER PT J AU Srikumaran, U Hannan, C Higgins, LD Warner, JJP AF Srikumaran, Uma Hannan, Casey Higgins, Laurence D. Warner, Jon J. P. TI Value and Health Care Policy Ramifications of Rotator Cuff Repair SO Techniques in Orthopaedics LA English DT Article DE rotator cuff tears; rotator cuff repair; value; costs ID ARTHROSCOPIC SINGLE-ROW; SUTURE ANCHOR TECHNIQUE; MODIFIED MASON-ALLEN; TRANSOSSEOUS SUTURE; BIOMECHANICAL EVALUATION; TEARS; TENDON; INTEGRITY; FIXATION; SUPRASPINATUS AB The societal burden of rotator cuff disease continues to increase with the aging of our population. Rotator cuff repairs have also become increasingly common over the last 2 decades. In our current cost conscious health care environment it is imperative to understand the value delivered to patients by various interventions. Value is most often equated with outcomes relative to the costs associated with care. To determine the value of different interventions, a thorough understanding of how to measure and interpret patient outcomes is crucial. In addition, calculating costs can be complex and physicians are often unaware of the costs related to their own decisions. Despite the complexities of measuring value, its benefits include heightened transparency in health care delivery, aligning stakeholders, and avoiding the trap of focussing solely on cost reductions, which may endanger effective treatment modalities. C1 [Srikumaran, Uma; Hannan, Casey] Johns Hopkins Univ, Dept Orthopaed Surg, Baltimore, MD USA. [Higgins, Laurence D.] Brigham & Womens Hosp, Dept Orthoped Surg, Sports Med & Shoulder Serv, 75 Francis St, Boston, MA 02115 USA. [Warner, Jon J. P.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Shoulder Serv, Boston, MA 02114 USA. RP Warner, JJP (reprint author), 55 Fruit St YAW 3G, Boston, MA 02114 USA. EM jwarner@mgh.harvard.edu NR 62 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-9698 EI 2333-0600 J9 TECH ORTHOP JI Tech. Orthop. PD JUN PY 2016 VL 31 IS 2 BP 120 EP 126 DI 10.1097/BTO.0000000000000177 PG 7 WC Orthopedics SC Orthopedics GA ED6ZQ UT WOS:000389005900011 ER PT J AU Orlando, G Law, PJ Palin, K Tuupanen, S Gylfe, A Hanninen, UA Cajuso, T Tanskanen, T Kondelin, J Kaasinen, E Sarin, AP Kaprio, J Eriksson, JG Rissanen, H Knekt, P Pukkala, E Jousilahti, P Salomaa, V Ripatti, S Palotie, A Jarvinen, H Renkonen-Sinisalo, L Lepisto, A Bohm, J Mecklin, JP Al-Tassan, NA Palles, C Martin, L Barclay, E Tenesa, A Farrington, S Timofeeva, MN Meyer, BF Wakil, SM Campbell, H Smith, CG Idziaszczyk, S Maughan, TS Kaplan, R Kerr, R Kerr, D Buchanan, DD Win, AK Hopper, J Jenkins, M Lindor, NM Newcomb, PA Gallinger, S Conti, D Schumacher, F Casey, G Taipale, J Cheadle, JP Dunlop, MG Tomlinson, IP Aaltonen, LA Houlston, RS AF Orlando, Giulia Law, Philip J. Palin, Kimmo Tuupanen, Sari Gylfe, Alexandra Hanninen, Ulrika A. Cajuso, Tatiana Tanskanen, Tomas Kondelin, Johanna Kaasinen, Eevi Sarin, Antti-Pekka Kaprio, Jaakko Eriksson, Johan G. Rissanen, Harri Knekt, Paul Pukkala, Eero Jousilahti, Pekka Salomaa, Veikko Ripatti, Samuli Palotie, Aarno Jarvinen, Heikki Renkonen-Sinisalo, Laura Lepisto, Anna Bohm, Jan Mecklin, Jukka-Pekka Al-Tassan, Nada A. Palles, Claire Martin, Lynn Barclay, Ella Tenesa, Albert Farrington, Susan Timofeeva, Maria N. Meyer, Brian F. Wakil, Salma M. Campbell, Harry Smith, Christopher G. Idziaszczyk, Shelley Maughan, Timothy S. Kaplan, Richard Kerr, Rachel Kerr, David Buchanan, Daniel D. Win, Aung Ko Hopper, John Jenkins, Mark Lindor, Noralane M. Newcomb, Polly A. Gallinger, Steve Conti, David Schumacher, Fred Casey, Graham Taipale, Jussi Cheadle, Jeremy P. Dunlop, Malcolm G. Tomlinson, Ian P. Aaltonen, Lauri A. Houlston, Richard S. TI Variation at 2q35 (PNKD and TMBIM1) influences colorectal cancer risk and identifies a pleiotropic effect with inflammatory bowel disease SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; INTESTINAL INFLAMMATION; FUNCTIONAL VARIATION; CROHNS-DISEASE; COHORT PROFILE; BIRTH COHORT; METAANALYSIS; IMPUTATION; VARIANTS AB To identify new risk loci for colorectal cancer (CRC), we conducted a meta-analysis of seven genome-wide association studies (GWAS) with independent replication, totalling 13 656 CRC cases and 21 667 controls of European ancestry. The combined analysis identified a new risk association for CRC at 2q35 marked by rs992157 (P = 3.15 x 10(-8), odds ratio = 1.10, 95% confidence interval = 1.06-1.13), which is intronic to PNKD (paroxysmal non-kinesigenic dyskinesia) and TMBIM1 (transmembrane BAX inhibitor motif containing 1). Intriguingly this susceptibility single-nucleotide polymorphism (SNP) is in strong linkage disequilibrium (r(2) = 0.90, D' = 0.96) with the previously discovered GWAS SNP rs2382817 for inflammatory bowel disease (IBD). Following on from this observation we examined for pleiotropy, or shared genetic susceptibility, between CRC and the 200 established IBD risk loci, identifying an additional 11 significant associations (false discovery rate [FDR]) < 0.05). Our findings provide further insight into the biological basis of inherited genetic susceptibility to CRC, and identify risk factors that may influence the development of both CRC and IBD. C1 [Orlando, Giulia; Law, Philip J.; Houlston, Richard S.] Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England. [Palin, Kimmo; Tuupanen, Sari; Gylfe, Alexandra; Hanninen, Ulrika A.; Cajuso, Tatiana; Tanskanen, Tomas; Kondelin, Johanna; Kaasinen, Eevi; Taipale, Jussi; Aaltonen, Lauri A.] Univ Helsinki, Genome Scale Biol Res Program, Res Programs Unit, FIN-00014 Helsinki, Finland. [Palin, Kimmo; Tuupanen, Sari; Gylfe, Alexandra; Hanninen, Ulrika A.; Cajuso, Tatiana; Tanskanen, Tomas; Kondelin, Johanna; Kaasinen, Eevi; Taipale, Jussi; Aaltonen, Lauri A.] Univ Helsinki, Dept Med & Clin Genet, Medicum, FIN-00014 Helsinki, Finland. [Sarin, Antti-Pekka; Kaprio, Jaakko; Ripatti, Samuli; Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland, FIN-00014 Helsinki, Finland. [Kaprio, Jaakko; Rissanen, Harri; Knekt, Paul; Jousilahti, Pekka; Salomaa, Veikko] Natl Inst Hlth & Welf, Helsinki 00271, Finland. [Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki 00250, Finland. [Eriksson, Johan G.] Univ Helsinki, Unit Gen Practice & Primary Hlth Care, FIN-00014 Helsinki, Finland. [Eriksson, Johan G.] Helsinki Univ Hosp, Helsinki 00014, Finland. [Pukkala, Eero] Finnish Canc Registry, Inst Stat & Epidemiol Canc Res, Helsinki 00130, Finland. [Pukkala, Eero] Univ Tampere, Sch Hlth Sci, Tampere 33014, Finland. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Palotie, Aarno] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Jarvinen, Heikki] Univ Helsinki, Cent Hosp, Hosp Dist Helsinki & Uusimaa, Dept Surg, Helsinki 00029, Finland. [Renkonen-Sinisalo, Laura; Lepisto, Anna] Helsinki Univ Hosp, Abdominal Ctr, Dept Surg, Helsinki 00029, Finland. [Bohm, Jan] Cent Finland Cent Hosp, Dept Pathol, Jyvaskyla 40620, Finland. [Mecklin, Jukka-Pekka] Univ Eastern Finland, Jyvaskyla Cent Hosp, Dept Surg, Jyvaskyla 40620, Finland. [Al-Tassan, Nada A.; Meyer, Brian F.; Wakil, Salma M.] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 12713, Saudi Arabia. [Palles, Claire; Martin, Lynn; Barclay, Ella; Tomlinson, Ian P.] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Palles, Claire; Martin, Lynn; Barclay, Ella; Tomlinson, Ian P.] NIHR Comprehens Biomed Res Ctr, Oxford OX3 7BN, England. [Tenesa, Albert; Farrington, Susan; Timofeeva, Maria N.; Dunlop, Malcolm G.] Univ Edinburgh, Colon Canc Genet Grp, Edinburgh EH4 2XU, Midlothian, Scotland. [Tenesa, Albert; Farrington, Susan; Timofeeva, Maria N.; Dunlop, Malcolm G.] Western Gen Hosp, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland. [Tenesa, Albert] Univ Edinburgh, Roslin Inst, Roslin EH25 9RG, Midlothian, Scotland. [Campbell, Harry] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland. [Smith, Christopher G.; Idziaszczyk, Shelley; Cheadle, Jeremy P.] Cardiff Univ, Sch Med, Inst Canc & Genet, Cardiff CF14 4XN, S Glam, Wales. [Maughan, Timothy S.] Univ Oxford, CRUK MRC Oxford Inst Radiat Oncol, Oxford OX3 7DQ, England. [Kaplan, Richard] MRC Clin Trials Unit, Aviat House, London WC2B 6NH, England. [Kerr, Rachel] Univ Oxford, Churchill Hosp, Oxford Canc Ctr, Dept Oncol, Oxford OX3 7LE, England. [Kerr, David] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Lab Sci, Oxford OX3 7LE, England. [Buchanan, Daniel D.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Colorectal Oncogen Grp, Melbourne, Vic 3010, Australia. [Buchanan, Daniel D.; Win, Aung Ko; Hopper, John; Jenkins, Mark] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia. [Lindor, Noralane M.] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ 85259 USA. [Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98109 USA. [Gallinger, Steve] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Conti, David; Schumacher, Fred; Casey, Graham] Univ Southern Calif, Dept Prevent Med, Los Angeles, CA 90033 USA. [Taipale, Jussi] Karolinska Inst, SciLife Ctr, Dept Biosci & Nutr, SE-14183 Stockholm, Sweden. RP Houlston, RS (reprint author), Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England. EM richard.houlston@icr.ac.uk RI Gallinger, Steven/E-4575-2013; Dunlop, Malcolm/F-1973-2011; OI Dunlop, Malcolm/0000-0002-3033-5851; Kaprio, Jaakko/0000-0002-3716-2455; Houlston, Richard/0000-0002-5268-0242 FU Academy of Finland [Finnish Center of Excellence] [250345]; Jane and Aatos Erkko Foundation; Finnish Cancer Society; European Research Council [ERC] [268648]; Sigrid Juselius Foundation; SYSCOL; Nordic Information for Action eScience Center (NIASC); Nordic Center of Excellence - NordForsk [62721]; Kuopio University Hospital [B1401]; Academy of Finland [271642, 263164, 100499, 205585, 265240, 263278]; Ministry of Education and Culture, Finland; Finnish Academy [139635]; ENGAGE-European Network for Genetic and Genomic Epidemiology [201413]; National Institute of Alcohol Abuse and Alcoholism [AA-12502, AA-00145, K02AA018755]; Cancer Research UK [C1298/A8362, C348/A12076]; National Cancer Research Network; NHS via the Biological Research Centre of the National Institute for Health Research at the Royal Marsden Hospital NHS Trust; Oxford Comprehensive Biomedical Research Centre; EU FP7 CHIBCHA; European Union [258236]; FP7 collaborative project SYSCOL; COST Action in the UK [BM1206]; Cancer Research UK; Medical Research Council; National Institute of Health Research Cancer Research Network; Bobby Moore Fund from Cancer Research UK; Tenovus; Kidani Trust; Cancer Research Wales; National Institute for Social Care and Health Research Cancer Genetics Biomedical Research Unit; KFSHRC; National Cancer Institute, National Institutes of Health [UM1 CA167551, U01 CA122839, R01 CA143237]; CCFR centre: Australasian Colorectal Cancer Family Registry [U01 CA074778, U01/U24 CA097735]; CCFR centre: USC Consortium Colorectal Cancer Family Registry [U01/U24 CA074799]; CCFR centre: Mayo Clinic Cooperative Familial Registry for Colon Cancer Studies [U01/U24 CA074800]; CCFR centre: Ontario Familial Colorectal Cancer Registry [U01/U24 CA074783]; CCFR centre: Seattle Colorectal Cancer Family Registry [U01/U24 CA074794]; CCFR centre: University of Hawaii Colorectal Cancer Family Registry [U01/U24 CA074806]; Cancer Surveillance System of the Fred Hutchinson Cancer Research Center [N01-CN-67009, N01-PC-35142]; Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute [HHSN2612013000121]; Fred Hutchinson Cancer Research Center; National Cancer Institute's Surveillance, Epidemiology and End Results Program (SEER) [N01-PC-67001, N01-PC-35137, HHSN26120100037C, HHSN261201300009I]; National Cancer Institute's Surveillance, Epidemiology and End Results Program [HHSN261201000035C, HHSN261201000034C]; Centers for Disease Control and Prevention's National Program of Cancer Registries [U58DP003862-01]; COAF: Charity Open Access Fund; [090532/Z/09/Z] FX In Finland, this work was supported by grants from the Academy of Finland [Finnish Center of Excellence Program 2012-2017, 250345], the Jane and Aatos Erkko Foundation, the Finnish Cancer Society [personal grant to K.P.], the European Research Council [ERC; 268648], the Sigrid Juselius Foundation, SYSCOL, the Nordic Information for Action eScience Center (NIASC), the Nordic Center of Excellence financed by NordForsk [project 62721, personal grant to K.P.] and State Research Funding of Kuopio University Hospital [B1401]. We acknowledge the computational resources provided by the ELIXIR node, hosted at the CSC-IT Center for Science, Finland, and funded by the Academy of Finland [grants 271642 and 263164], the Ministry of Education and Culture, Finland. V.S. was supported by the Finnish Academy [grant number 139635]. Sample collection and genotyping in the Finnish Twin Cohort has been supported by the Wellcome Trust Sanger Institute, ENGAGE-European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007 [grant agreement number 201413], the National Institute of Alcohol Abuse and Alcoholism [grants AA-12502 and AA-00145 to Richard J. Rose and K02AA018755 to Danielle M. Dick] and the Academy of Finland [grants 100499, 205585, 265240 and 263278 to J.K.].; At the Institute of Cancer Research, this work was supported by Cancer Research UK [C1298/A8362-Bobby Moore Fund for Cancer Research UK]. Additional support was provided by the National Cancer Research Network and the NHS via the Biological Research Centre of the National Institute for Health Research at the Royal Marsden Hospital NHS Trust. In Edinburgh, the work was supported by Programme Grant funding from Cancer Research UK [C348/A12076]. In Oxford, additional funding was provided by the Oxford Comprehensive Biomedical Research Centre [to C.P. and I.P.M.T.] and the EU FP7 CHIBCHA grant [I.P.M.T.]. Core infrastructure support to the Wellcome Trust Centre for Human Genetics, Oxford was provided by grant [090532/Z/09/Z]. We are grateful to many colleagues within UK Clinical Genetics Departments (for CORGI) and to many collaborators who participated in the VICTOR and QUASAR2 trials. We also thank colleagues from the UK National Cancer Research Network (for NSCCG). Support from the European Union [FP7/207-2013, grant 258236] and FP7 collaborative project SYSCOL and COST Action in the UK is also acknowledged [BM1206]. The COIN and COIN-B trials were funded by Cancer Research UK and the Medical Research Council and were conducted with the support of the National Institute of Health Research Cancer Research Network. COIN and COIN-B translational studies were supported by the Bobby Moore Fund from Cancer Research UK, Tenovus, the Kidani Trust, Cancer Research Wales and the National Institute for Social Care and Health Research Cancer Genetics Biomedical Research Unit (2011-2014) [all awarded to J.P.C.]. N.A.A., B.F.M. and S.M.W. were funded and supported by KFSHRC.; The work of the Colon Cancer Family Registry (CCFR) was supported by from the National Cancer Institute [grant UM1 CA167551], National Institutes of Health and through cooperative agreements with the following CCFR centres: Australasian Colorectal Cancer Family Registry [U01 CA074778, U01/U24 CA097735], USC Consortium Colorectal Cancer Family Registry [U01/U24 CA074799], Mayo Clinic Cooperative Familial Registry for Colon Cancer Studies [U01/U24 CA074800], Ontario Familial Colorectal Cancer Registry [U01/U24 CA074783], Seattle Colorectal Cancer Family Registry [U01/U24 CA074794] and University of Hawaii Colorectal Cancer Family Registry [U01/U24 CA074806].; The CCFR Illumina GWAS was supported by funding from the National Cancer Institute, National Institutes of Health [U01 CA122839 and R01 CA143237 to G.C.]. Seattle CCFR research was also supported by the Cancer Surveillance System of the Fred Hutchinson Cancer Research Center [Control Nos. N01-CN-67009 (1996-2003), N01-PC-35142 (2003-2010)] and the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute [Contract No. HHSN2612013000121 (2010-2017)] with additional support from the Fred Hutchinson Cancer Research Center. The collection of cancer incidence data for the State of Hawai'i used in this study was supported by the Hawai'i Department of Health as part of the statewide cancer reporting program mandated by Hawai'i Revised Statutes; the National Cancer Institute's Surveillance, Epidemiology and End Results Program (SEER) awarded to the University of Hawai'i [Control Nos. N01-PC-67001 (1996-2003), N01-PC-35137 (2003-2010), Contract Nos. HHSN26120100037C (2010-2013), HHSN261201300009I (2010-current)]. The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of Hawai'i, Department of Health, the National Cancer Institute, SEER Program or their Contractors and Subcontractors is not intended nor should be inferred. The collection of cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute's Surveillance, Epidemiology and End Results Program [under contract HHSN261201000035C] awarded to the University of Southern California, and [contract HHSN261201000034C] awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement [U58DP003862-01] awarded to the California Department of Public Health. The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of California, Department of Public Health the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors is not intended nor should be inferred. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the CCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the CCFR. Funding to pay the Open Access publication charges for this article was provided by COAF: Charity Open Access Fund. NR 74 TC 0 Z9 0 U1 7 U2 7 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 JUN 1 PY 2016 VL 25 IS 11 BP 2349 EP 2359 DI 10.1093/hmg/ddw087 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA ED0TK UT WOS:000388554700019 PM 27005424 ER PT J AU Staziaki, PV Kim, P Vadvala, HV Ghoshhajra, BB AF Staziaki, Pedro Vinicius Kim, Phillip Vadvala, Harshna V. Ghoshhajra, Brian B. TI Medical Registry Data Collection Efficiency: A Crossover Study Comparing Web-Based Electronic Data Capture and a Standard Spreadsheet SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE electronic data capture; clinical research; translational research; registry; data management ID CLINICAL-RESEARCH; INTERNET; TRIALS AB Background: Electronic medical records and electronic data capture (EDC) have changed data collection in clinical and translational research. However, spreadsheet programs, such as Microsoft Excel, are still used as data repository to record and organize patient data for research. Objective: The objective of this study is to assess the efficiency of EDC as against a standard spreadsheet in regards to time to collect data and data accuracy, measured in number of errors after adjudication. Methods: This was a crossover study comparing the time to collect data in minutes between EDC and a spreadsheet. The EDC tool used was Research Electronic Data Capture (REDCap), whereas the spreadsheet was Microsoft Excel. The data collected was part of a registry of patients who underwent coronary computed tomography angiography in the emergency setting. Two data collectors with the same experience went over the same patients and collected relevant data on a case report form identical to the one used in our Emergency Department (ED) registry. Data collection tool was switched after the patient that represented half the cohort. For this, the patient cohort was exactly 30 days of our ED coronary Computed Tomography Angiography registry and the point of crossover was determined beforehand to be 15 days. We measured the number of patients admitted, and time to collect data. Accuracy was defined as absence of blank fields and errors, and was assessed by comparing data between data collectors and counting every time the data differed. Statistical analysis was made using paired t-test. Results: The study included 61 patients (122 observations) and 55 variables. The crossover occurred after the 30th patient. Mean time to collect data using EDC in minutes was 6.2 +/- 2.3, whereas using Excel was 8.0 +/- 2.0 (P <. 001), a difference of 1.8 minutes between both means (22%). The cohort was evenly distributed with 3 admissions in the first half of the crossover and 4 in the second half. We saw 2 (< 0.1%) continuous variable typos in the spreadsheet that a single data collector made. There were no blank fields. The data collection tools showed no differences in accuracy of data on comparison. Conclusions: Data collection for our registry with an EDC tool was faster than using a spreadsheet, which in turn allowed more efficient follow-up of cases. C1 [Staziaki, Pedro Vinicius; Kim, Phillip; Vadvala, Harshna V.; Ghoshhajra, Brian B.] Harvard Med Sch, Dept Radiol, Massachusetts Gen Hosp, 165 Cambridge St Suite 400, Boston, MA 02114 USA. RP Ghoshhajra, BB (reprint author), Harvard Med Sch, Dept Radiol, Massachusetts Gen Hosp, 165 Cambridge St Suite 400, Boston, MA 02114 USA. EM bghoshhajra@mgh.harvard.edu OI Staziaki, Pedro/0000-0003-3219-3815; Vadvala, Harshna/0000-0002-2067-8201; Ghoshhajra, Brian/0000-0002-3865-3432 NR 15 TC 0 Z9 0 U1 1 U2 1 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PD JUN PY 2016 VL 18 IS 6 AR e141 DI 10.2196/jmir.5576 PG 6 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA EC9WO UT WOS:000388495200022 PM 27277523 ER PT J AU El-Jawahri, A Keenan, T Abel, GA Steensma, DP LeBlanc, TW Chen, YB Hobbs, G Traeger, L Fathi, AT DeAngelo, DJ Wadleigh, M Ballen, KK Amrein, PC Stone, RM Temel, JS AF El-Jawahri, Areej Keenan, Tanya Abel, Gregory A. Steensma, David P. LeBlanc, Thomas W. Chen, Yi-Bin Hobbs, Gabriela Traeger, Lara Fathi, Amir T. DeAngelo, Daniel J. Wadleigh, Martha Ballen, Karen K. Amrein, Philip C. Stone, Richard M. Temel, Jennifer S. TI Potentially avoidable hospital admissions in older patients with acute myeloid leukaemia in the USA: a retrospective analysis SO LANCET HAEMATOLOGY LA English DT Article ID OF-LIFE CARE; READMISSIONS; METAANALYSIS; REHOSPITALIZATIONS; PREFERENCES; POPULATION; CANCER; ADULTS; RATES AB Background Older adults (>= 60 years of age) with acute myeloid leukaemia spend a substantial proportion of their life in hospital after diagnosis. We examined reasons for their hospital admissions and identified potentially avoidable hospital admissions (PAH) in this age group in the USA. Methods In this retrospective analysis, we examined the reasons for hospital admissions in older patients diagnosed with and treated for acute myeloid leukaemia at two tertiary care hospitals in the USA. We included patients receiving intensive induction chemotherapy or non-intensive treatment. We excluded those with acute promyelocytic leukaemia, those seen only for a one-time consultation who received primary treatment elsewhere, and those who received supportive care alone. We identified the eligible cohort using the Dana-Farber Cancer Institute and Massachusetts General Hospital Leukemia Clinical Research Information Systems database. Practising oncologists used a consensus-driven medical record review process to identify the primary reason for each hospital admission and categorise it as potentially avoidable or not avoidable on the basis of an adaptation of Graham's criteria for PAH. We used multivariable logistic regression analyses to identify predictors of PAH. Findings Between May 1, 2005, and Dec 23, 2011, we assessed 1040 hospital admissions (excluding initial admission for diagnosis) in 329 consecutively admitted patients. The most common primary reasons for hospital admissions were: fever or infection (396 [38%]), planned admission for chemotherapy or transplantation (391 [38%]), and uncontrolled symptoms (102 [10%]). We identified 172 (27%) of 649 unplanned hospital admissions as potentially avoidable; among these admissions, 82 (48%) were readmissions because of previous premature hospital discharge, 32 (19%) because of problems that could have been managed in the outpatient setting, and 26 (15%) because of failure of timely outpatient follow-up. In a mixed logistic regression model, higher education (odds ratio 1.43 [95% CI 1.01-2.00]; p=0.04) and receipt of non-intensive induction chemotherapy (1.97 [1.25-3.10]; p= 0.003) were predictors of PAH. Interpretation Although many hospital admissions in older patients with acute myeloid leukaemia are unavoidable and driven by the illness course and its treatment, a substantial proportion are potentially avoidable. Future interventions to reduce PAH in this population are clearly warranted. C1 [El-Jawahri, Areej; Keenan, Tanya; Chen, Yi-Bin; Hobbs, Gabriela; Traeger, Lara; Fathi, Amir T.; Ballen, Karen K.; Amrein, Philip C.; Temel, Jennifer S.] Massachusetts Gen Hosp, Dept Hematol & Oncol, Bone Marrow Transplant Program, Boston, MA 02114 USA. [El-Jawahri, Areej; Keenan, Tanya; Abel, Gregory A.; Steensma, David P.; Chen, Yi-Bin; Hobbs, Gabriela; Traeger, Lara; Fathi, Amir T.; DeAngelo, Daniel J.; Wadleigh, Martha; Ballen, Karen K.; Amrein, Philip C.; Stone, Richard M.; Temel, Jennifer S.] Harvard Med Sch, Boston, MA USA. [Abel, Gregory A.; Steensma, David P.; DeAngelo, Daniel J.; Wadleigh, Martha; Stone, Richard M.] Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. [LeBlanc, Thomas W.] Duke Univ, Med Ctr, Sch Med, Durham, NC 27710 USA. RP El-Jawahri, A (reprint author), Dept Hematol & Oncol, Bone Marrow Transplant Program, Boston, MA 02114 USA. EM ael-jawahri@partners.org FU National Cancer Institute Federal Share Program (JST) [K24 CA 181253]; National Palliative Care Research Center (AE-J); Cambia Health Foundation FX This study is funded by the National Cancer Institute Federal Share Program (JST; K24 CA 181253), the National Palliative Care Research Center (AE-J), and the Cambia Health Foundation (TWL). NR 29 TC 0 Z9 0 U1 2 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2352-3026 J9 LANCET HAEMATOL JI Lancet Haematol. PD JUN PY 2016 VL 3 IS 6 BP E276 EP E283 DI 10.1016/S2352-3026(16)30024-2 PG 8 WC Hematology SC Hematology GA ED7SB UT WOS:000389069100008 PM 27264037 ER PT J AU Sacco, A Fenotti, A Bazzana, S Imberti, L Rossi, G Patterson, CJ Treon, SP Ghobrial, IM Roccaro, AM AF Sacco, Antonio Fenotti, Adriano Bazzana, Stefano Imberti, Luisa Rossi, Giuseppe Patterson, Christopher J. Treon, Steven P. Ghobrial, Irene M. Roccaro, Aldo M. TI Epigenomics in Waldenstrom's macroglobulinaemia SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Article DE Waldenstrom's macroglobulinaemia; Epigenomic; Histone acetylation; microRNAs ID HISTONE DEACETYLASE INHIBITION; B-CELL LYMPHOMAS; MICRORNA EXPRESSION; MULTIPLE-MYELOMA; CANCER; ACETYLATION; THERAPY; LEUKEMIA; DISEASE; GENES AB Epigenomics refers to study of the epigenome, which represents changes in gene expression that are not induced by DNA sequence aberrations. For instance, DNA methylation, histone acetylation and microRNAs may modulate gene expression without altering the gene sequence. Waldenstrom's macroglobulinaemia (WM) is a low-grade B-cell lymphoma, classified as lymphoplasmacytic lymphoma, characterized by the presence of clonal lymphoplasmacytic cells in the bone marrow and serum monoclonal immunoglobulin-M in the circulation. It is a rare disease and, although indolent, it remains incurable with a median overall survival of 5-6 years. Most patients succumb to disease progression. WM cells present with aberrant histone hypoacetylation that may be explained, at least in part, via deregulated microRNAs, thus suggesting the use of histone deacetylase inhibitors or microRNA-based therapies in this disease. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Sacco, Antonio; Imberti, Luisa; Rossi, Giuseppe; Roccaro, Aldo M.] ASST Spedali Civili, CREA Lab, Dept Med Oncol, Ple Spedali Civili 1, I-25121 Brescia, Italy. [Fenotti, Adriano] ASST Spedali Civili, SITRA, Brescia, Italy. [Bazzana, Stefano] ASST Spedali Civili, Coll IPASVI, Brescia, Italy. [Sacco, Antonio; Patterson, Christopher J.; Treon, Steven P.; Ghobrial, Irene M.; Roccaro, Aldo M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Roccaro, AM (reprint author), ASST Spedali Civili, CREA Lab, Dept Med Oncol, Ple Spedali Civili 1, I-25121 Brescia, Italy. EM aldomaria.roccaro@asst-spedalicivili.it NR 34 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-6926 EI 1532-1924 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD JUN PY 2016 VL 29 IS 2 BP 156 EP 160 DI 10.1016/j.beha.2016.08.022 PG 5 WC Hematology SC Hematology GA ED0PN UT WOS:000388544500004 PM 27825461 ER PT J AU Castillo, JJ Hunter, ZR Yang, G Argyropoulos, K Palomba, ML Treon, SP AF Castillo, Jorge J. Hunter, Zachary R. Yang, Guang Argyropoulos, Kimon Palomba, M. Lia Treon, Steven P. TI Future therapeutic options for patients with Waldenstrom macroglobulinemia SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Article DE BTK; BCL2; CD38; CXCR4; MYD88; Waldenstrom ID CHRONIC LYMPHOCYTIC-LEUKEMIA; TYROSINE KINASE BTK; RELAPSED/REFRACTORY MULTIPLE-MYELOMA; ORAL PROTEASOME INHIBITOR; L265P SOMATIC MUTATION; PHASE-1 CLINICAL-TRIAL; END RESULTS DATABASE; MYD88 L265P; ANTITUMOR-ACTIVITY; IN-VIVO AB Waldenstrom macroglobulinemia (WM) is a rare lymphoma characterized by the accumulation of IgM-producing lymphoplasmacytic cells. Although WM patients can experience prolonged remissions, the disease invariably recurs. Therefore, novel treatments associated with higher success rates and lower toxicity profiles are needed. The discovery of recurrent mutations in the MYD88 and CXCR4 genes has unraveled potential therapeutic targets in WM patients. As a result of these findings and based on the design and execution of a prospective clinical trial, the FDA granted approval to ibrutinib, an oral Bruton tyrosine kinase (BTK) inhibitor, to treat patients with symptomatic WM. The present review focuses on potential therapies that could change the landscape of treatment of patients with WM, specifically focusing on inhibitors or antagonists or the proteasome, BTK, CD38, BCL2 and the CXCR4 and MYD88 genes themselves. Novel agents with novel mechanisms of action should be evaluated in the context of carefully designed clinical trials. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Castillo, Jorge J.; Hunter, Zachary R.; Yang, Guang; Treon, Steven P.] Harvard Med Sch, Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, Boston, MA USA. [Argyropoulos, Kimon; Palomba, M. Lia] Mem Sloan Kettering Canc Ctr, Div Hematol & Oncol, 1275 York Ave, New York, NY 10021 USA. RP Castillo, JJ (reprint author), 450 Brookline Ave,Mayer 221, Boston, MA 02215 USA. EM jorgej_castillo@dfci.harvard.edu OI Castillo, Jorge/0000-0001-9490-7532; Hunter, Zachary/0000-0002-1689-1691 FU Abbvie; Gilead; Millennium; Pharmacyclics; Janssen; Onyx FX JJC received honoraria from Alexion, Biogen, Celgene and Otsuka, and research funding from Abbvie, Gilead, Millennium and Pharmacyclics. SPT received research funding and/or honoraria from Gilead, Janssen, Onyx and Pharmacyclics. MLP has received honoraria from Pharmacyclics. NR 78 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-6926 EI 1532-1924 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD JUN PY 2016 VL 29 IS 2 BP 206 EP 215 DI 10.1016/j.beha.2016.08.021 PG 10 WC Hematology SC Hematology GA ED0PN UT WOS:000388544500010 PM 27825467 ER PT J AU Mustapha, JA Diaz-Sandoval, LJ Jaff, MR Adams, G Beasley, R Finton, S McGoff, T Miller, LE Ansari, M Saab, F AF Mustapha, J. A. Diaz-Sandoval, Larry J. Jaff, Michael R. Adams, George Beasley, Robert Finton, Sara McGoff, Theresa Miller, Larry E. Ansari, Mohammad Saab, Fadi TI Ultrasound-Guided Arterial Access: Outcomes Among Patients With Peripheral Artery Disease and Critical Limb Ischemia Undergoing Peripheral Interventions SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Article DE peripheral interventions; peripheral vascular disease; critical limb ischemia; access-site management ID CENTRAL VENOUS CANNULATION; FEMORAL-ARTERY; CLINICAL-TRIAL; PUNCTURE; METAANALYSIS; POPLITEAL; GUIDANCE; RECANALIZATION; COMPLICATIONS; FLUOROSCOPY AB Objective. Arterial cannulation is a vital component of endovascular interventions and often unconventional access approaches are required due to disease complexity. Historically, varying maneuvers have been utilized to obtain arterial access. Lack of consensus exists regarding the safest and most effective method. This study examined the feasibility and immediate outcomes of ultrasound-guided access in traditional and advanced access approaches. Methods. Data were analyzed from a cohort of 407 patients enrolled in the Peripheral RegIstry of Endovascular Clinical OutcoMEs (PRIME). The 407 patients underwent 649 procedures with 896 access sites utilized. Access success, immediate outcomes, complications, and length of hospital stay were analyzed. Results. Mean age was 70 years, and 67% were male. The majority of patients had critical limb ischemia (58%), 39% were Rutherford classification III. Most commonly utilized access sites were common femoral retrograde, common femoral antegrade, posterior tibial, and anterior tibial arteries (34.6%, 33.0%, 12.1%, and 12.1%, respectively). Mean number of attempts was 1.2, 1.2, 1.5, and 1.4, respectively; median time to access was 39, 45, 41, and 59 seconds, respectively; and access success rate was 99.4%, 97.3%, 90.7%, and 92.6%; respectively. Access-site combinations utilized were femoral antegrade (n = 188), femoral retrograde (n = 185), dual femoral/tibio-pedal (n = 130), dual femoral retrograde (n = 44), retrograde tibio-pedal (n = 73), and other (n = 29). Access-related complications were low overall: hematoma (1.2%), bleeding requiring transfusion/intervention (1.7%), pseudoaneurysm (1.7%), arteriovenous fistula (0.3%), aneurysm (0%), compartment syndrome (0%), and death (0%). Conclusion. Utilization of ultrasound-guided arterial access in this complex cohort was shown to be safe and effective regardless of arterial bed and approach. C1 [Mustapha, J. A.; Diaz-Sandoval, Larry J.; Finton, Sara; McGoff, Theresa; Ansari, Mohammad; Saab, Fadi] Metro Hlth Hosp, 5900 Byron Ctr SW,POB 9490, Wyoming, MI 49519 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Adams, George] Univ N Carolina, REX Healthcare, Raleigh, NC USA. [Beasley, Robert] Mt Sinai Med Ctr, Miami, FL USA. [Miller, Larry E.] Miller Sci Consulting Inc, Asheville, NC USA. RP Mustapha, JA (reprint author), Metro Hlth Hosp, 5900 Byron Ctr SW,POB 9490, Wyoming, MI 49519 USA. EM jihad.mustapha@metrogr.org FU Bard Peripheral Vascular; Terumo Interventional Systems; Cardiovascular Systems; Access Closure; Medtronic; Boston Scientific; Spectranetics FX The authors report unrestricted research grants to Metro Health to support the PRIME registry from Bard Peripheral Vascular, Terumo Interventional Systems, Cardiovascular Systems, Access Closure, Medtronic, Boston Scientific, and Spectranetics. NR 22 TC 1 Z9 1 U1 1 U2 1 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1042-3931 EI 1557-2501 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD JUN PY 2016 VL 28 IS 6 BP 259 EP 264 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EC9EN UT WOS:000388447200012 PM 27236010 ER PT J AU Clancy, CJ Meslin, C Badrane, H Cheng, SJ Losada, LC Nierman, WC Vergidis, P Clark, NL Nguyen, MH AF Clancy, Cornelius J. Meslin, Camille Badrane, Hassan Cheng, Shaoji Losada, Liliana C. Nierman, William C. Vergidis, Pascalis Clark, Nathan L. Nguyen, M. Hong TI Candida albicans Transcriptional Profiling Within Biliary Fluid From a Patient With Cholangitis, Before and After Antifungal Treatment and Surgical Drainage SO OPEN FORUM INFECTIOUS DISEASES LA English DT Article DE Candida albicans; cholangitis; fluconazole; RNA-Seq; transcriptional profiling ID DIFFERENTIAL EXPRESSION ANALYSIS; GENE-EXPRESSION; RNA-SEQ; HOST; INFECTION AB We used ribonucleic acid sequencing to profile Candida albicans transcription within biliary fluid from a patient with cholangitis; samples were collected before and after treatment with fluconazole and drainage. Candida albicans transcriptomes at the infection site distinguished treated from untreated cholangitis. After treatment, 1131 C. albicans genes were differentially expressed in biliary fluid. Up-regulated genes were enriched in hyphal growth, cell wall organization, adhesion, oxidation reduction, biofilm, and fatty acid and ergosterol biosynthesis. This is the first study to define Candida global gene expression during deep-seated human infection. Successful treatment of cholangitis induced C. albicans genes involved in fluconazole responses and pathogenesis. C1 [Clancy, Cornelius J.; Badrane, Hassan; Cheng, Shaoji; Vergidis, Pascalis; Nguyen, M. Hong] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Clancy, Cornelius J.] Univ Pittsburgh, Sch Med, Div Infect Dis, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. [Meslin, Camille; Clark, Nathan L.] Univ Pittsburgh, Sch Med, Dept Computat & Syst Biol, Pittsburgh, PA 15260 USA. [Losada, Liliana C.; Nierman, William C.] J Craig Venter Inst, Rockville, MD USA. [Losada, Liliana C.] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Nguyen, MH (reprint author), Univ Pittsburgh, Scaife Hall,Suite 871,3550 Terrace St, Pittsburgh, PA 15261 USA. EM mhn5@pitt.edu NR 15 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 2328-8957 J9 OPEN FORUM INFECT DI JI Open Forum Infect. Dis. PD SUM PY 2016 VL 3 IS 3 DI 10.1093/ofid/ofw120 PG 5 WC Infectious Diseases SC Infectious Diseases GA ED0YZ UT WOS:000388571700016 ER PT J AU Climov, M Medeiros, E Farkash, EA Qiao, JZ Rousseau, CF Dong, SM Zawadzka, A Racki, WJ Al-Musa, A Sachs, DH Randolph, MA Huang, CA Bollenbach, TJ AF Climov, Mihail Medeiros, Erika Farkash, Evan A. Qiao, Jizeng Rousseau, Cecile F. Dong, Shumin Zawadzka, Agatha Racki, Waldemar J. Al-Musa, Ahmad Sachs, David H. Randolph, Mark A. Huang, Christene A. Bollenbach, Thomas J. TI Bioengineered Self-assembled Skin as an Alternative to Skin Grafts SO PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN LA English DT Article ID FULL-THICKNESS BURNS; CLINICAL-APPLICATIONS; IN-VITRO; TISSUE; SUBSTITUTES; EQUIVALENT; AUTOGRAFT; COLLAGEN; WOUNDS; RECONSTRUCTION AB For patients with extensive burns or donor site scarring, the limited availability of autologous and the inevitable rejection of allogeneic skin drive the need for new alternatives. Existing engineered biologic and synthetic skin analogs serve as temporary coverage until sufficient autologous skin is available. Here we report successful engraftment of a self-assembled bilayered skin construct derived from autologous skin punch biopsies in a porcine model. Dermal fibroblasts were stimulated to produce an extracellular matrix and were then seeded with epidermal progenitor cells to generate an epidermis. Autologous constructs were grafted onto partial-and full-thickness wounds. By gross examination and histology, skin construct vascularization and healing were comparable to autologous skin grafts and were superior to an autologous bilayered living cellular construct fabricated with fibroblasts cast in bovine collagen. This is the first demonstration of spontaneous vascularization and permanent engraftment of a self-assembled bilayered bioengineered skin that could supplement existing methods of reconstruction. C1 [Climov, Mihail; Farkash, Evan A.; Al-Musa, Ahmad; Sachs, David H.; Huang, Christene A.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA USA. [Medeiros, Erika; Qiao, Jizeng; Rousseau, Cecile F.; Dong, Shumin; Zawadzka, Agatha; Racki, Waldemar J.; Bollenbach, Thomas J.] Organogenesis Inc, Canton, MA USA. [Farkash, Evan A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Randolph, Mark A.] Massachusetts Gen Hosp, Plast Surg Res Lab, Boston, MA 02114 USA. RP Bollenbach, TJ (reprint author), 85 Dan Rd, Canton, MA 02021 USA.; Huang, CA (reprint author), 13th St CNY149-9019 TBRC, Boston, MA 02129 USA. EM cahuang@mgh.harvard.edu; tbollenb@gmail.com NR 37 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2169-7574 J9 PRS-GLOB OPEN JI PRS-GLOB. OPEN PD JUN PY 2016 VL 4 IS 6 AR e731 DI 10.1097/GOX.0000000000000723 PG 10 WC Surgery SC Surgery GA EC7ZG UT WOS:000388359100006 PM 27482479 ER PT J AU Anton, A Ratarasarn, K AF Anton, Andreea Ratarasarn, Kavita TI Pulmonary Function Testing and Role of Pulmonary Rehabilitation in the Elderly Population with Pulmonary Diseases SO CURRENT GERIATRICS REPORTS LA English DT Article DE Geriatric; Elderly; Pulmonary function; Respiratory function; Pulmonary rehabilitation; Physical activity; Quality of life ID RANDOMIZED CONTROLLED-TRIAL; OLDER-ADULTS; RESPIRATORY REHABILITATION; EXERCISE CAPACITY; LUNG-FUNCTION; COPD; ASTHMA; MORTALITY; DIAGNOSIS; WORKSHOP AB With an aging population worldwide, the incidence and prevalence of certain pulmonary conditions such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are increasing. Pulmonary function tests (PFTs) are helpful tools to confirm pulmonary disorders. However, in the elderly population, age-associated changes in PFTs increase the risk for over diagnosis of obstructive lung disease. Therefore, an individualized approach to diagnosis of pulmonary disorders is essential for optimal management. For patients with established pulmonary disorders, pulmonary rehabilitation is a valuable but underutilized therapeutic intervention which has been shown to improve patient's quality of life, exercise tolerance, and overall prognosis. Recent evidence confirms that benefits of pulmonary rehabilitation are similar between the elderly and younger populations. C1 [Anton, Andreea; Ratarasarn, Kavita] US Dept Vet Affairs, Zablocki VAMC, 5000 W Natl Ave, Milwaukee, WI 53295 USA. [Anton, Andreea; Ratarasarn, Kavita] Med Coll Wisconsin, Div Pulm Crit Care & Sleep Med, 9200 W Wisconsin Ave, Milwaukee, WI 53266 USA. RP Anton, A (reprint author), US Dept Vet Affairs, Zablocki VAMC, 5000 W Natl Ave, Milwaukee, WI 53295 USA.; Anton, A (reprint author), Med Coll Wisconsin, Div Pulm Crit Care & Sleep Med, 9200 W Wisconsin Ave, Milwaukee, WI 53266 USA. EM aturcu@mcw.edu NR 56 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 2196-7865 J9 CURR GERIATR REP JI Curr. Geriatr. Rep. PD JUN PY 2016 VL 5 IS 2 BP 117 EP 123 DI 10.1007/s13670-016-0164-y PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA EC1JR UT WOS:000387861200008 ER PT J AU Salerno, L Makris, N Pallanti, S AF Salerno, L. Makris, N. Pallanti, S. TI Sleep disorders in adult ADHD: a key feature SO JOURNAL OF PSYCHOPATHOLOGY-GIORNALE DI PSICOPATOLOGIA LA English DT Article DE ADHD; Attention deficit disorder; Sleep disorders ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; CHILDHOOD; METHYLPHENIDATE; ASSOCIATION; DEPRESSION; SYMPTOMS; CHILDREN; ONSET AB Objectives Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric disorder affecting individuals across the life span, and the relationship between ADHD and sleep poses several challenges in clinical practice. As ADHD symptoms overlap with those of sleep disorders, the aim of this paper is to summarise the state of art regarding the relationship between these conditions, in order to provide suggestions for future research and key elements to take into account during the diagnostic assessment of ADHD as well its clinical management. Methods We performed a PubMed search for articles published from 2005 to 2016, using the following key words: attention deficit disorder, ADHD, sleep disorders. The literature search was conducted in March 2016. Only articles written in English and providing data on adult population were considered. Results We found 773 articles matching keywords. Applying the above-mentioned exclusion criteria, only 30 resulted pertinent to our aim. Other articles from other databases were selected according to their importance, and then further filtered according to their capability in answering our research objectives. A total of 35 articles allowed us to identify the most frequently reported sleep disorders in adult ADHD, the potential neurobiological substrates at the basis of the similarities in symptomatology and the most important implications for clinical and research settings. Conclusions A poor sleep can worsen ADHD symptomatology, resulting in an increasing risk for accidents and health problems. An increased risk for depression has also been documented. Because of the overlapping symptomatology, the presence of a sleep disorder should be adequately screened during ADHD assessment and during the clinical management of the disorder. The similarities between symptoms of ADHD and those of a sleep disorder suggest certain basic disturbances in a potential common circuitry that require further exploration. The understanding of the causes accounting for the frequent co-occurrence of sleep disorders in people affected by ADHD may help to implement an effective treatment for improving quality of life of these patients. C1 [Salerno, L.] Inst Neurosci, Florence, Italy. [Makris, N.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Ctr Morphometr Anal, Boston, MA USA. [Makris, N.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Ctr Morphometr Anal, Boston, MA USA. [Pallanti, S.] Univ Florence, Dipartimento Neurosci Psicol Area Farmaco & Salut, Florence, Italy. [Pallanti, S.] UC Davis Hlth Syst, Dept Psychiat & Behav Sci, Sacramento, CA USA. [Pallanti, S.] Albert Einstein Coll Med, Dept Psychiat & Behav Sci, New York, NY USA. RP Salerno, L (reprint author), Inst Neurosci, Florence, Italy. EM luanasalerno@alice.it NR 35 TC 0 Z9 0 U1 2 U2 2 PU PACINI EDITORE PI PISA PA VIA DELLA GHERARDESCA-ZONA INDUSTRIALE OSPEDALETTO, 56121 PISA, ITALY SN 1592-1107 EI 2499-6904 J9 J PSYCHOPATHOL-G PSI JI J. Psychopathol.-G. Psicopatol. PD JUN PY 2016 VL 22 IS 2 BP 135 EP 140 PG 6 WC Psychiatry SC Psychiatry GA EC1RI UT WOS:000387884500005 ER PT J AU Sacco, J Baas, W Barnes, MA Luberto, C Talat, R Cotton, S AF Sacco, John Baas, Wesley Barnes, Mary Ann Luberto, Christina Talat, Rehab Cotton, Sian TI The Efficacy of Percutaneous Auricular Neurostimulation for Chemotherapy-Induced Peripheral Neuropathy: A Retrospective Chart Review SO MEDICAL ACUPUNCTURE LA English DT Article DE Auricular Acupuncture; Peripheral Neuropathy; Electroacupuncture ID ACUPUNCTURE; PAIN; STIMULATION; TRIAL; FMRI AB Background: Peripheral neuropathy is a common problem that can occur with chemotherapy treatment, resulting in pain, numbness, and reduced function. One promising, yet understudied, integrative care therapy that might offer pain relief for patients is a percutaneously placed, microchip-controlled pulsed neurotransmitter that provides electrical pulses to specific peripheral nerves in the ear. Objective: The purpose of this study was to examine the efficacy of this therapy for reducing pain and improving function in patients with chemotherapy-induced peripheral neuropathy (CIPN). Materials and Methods: A mixed-method retrospective chart review of patients receiving, from an integrative oncologist, percutaneous auricular neurostimulation (PANS) for CIPN was conducted. Nonparametric tests were used to examine pain scores pre-post treatment. A qualitative content analysis was used to examine pain and functional outcomes associated with treatment in those charts that did not have quantitative pain scores documented. Results: A total of 98 charts were reviewed, of which 58 charts met the study criteria. For the 18 patients that had pre-post pain scores available for quantitative analyses (M-age = 6 3 years; 67% female), pain scores significantly decreased after PANS (M-pre = 8.11 vs. M-post = 3.17; median change -5.0, p < 0.001), regardless of number of treatments (M=4.5; SD=2.5). Fifty-nine percent of patients with qualitative data reported marked improvements and 12.5% reported notable, yet minimal, reductions of pain and numbness following treatment. Conclusions: PANS was associated with significant improvements in both pain and function. Preliminary results suggest that PANS might be a useful nonpharmacologic treatment for patients with CIPN. Further controlled studies, using prospective research designs and active control groups, are warranted. C1 [Sacco, John] OHCare, Cincinnati, OH USA. [Sacco, John] Univ Cincinnati, Coll Med, Dept Med Educ, Cincinnati, OH USA. [Baas, Wesley] Southern Illinois Sch Med, Dept Surg, Div Urol, Springfield, IL USA. [Barnes, Mary Ann] St Elizabeth Hosp, Family Med Residency Program, Edgewood, KY USA. [Luberto, Christina] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. [Talat, Rehab; Cotton, Sian] Univ Cincinnati, Dept Family & Community Med, Div Integrat Med, 231 Albert Sabin Way,ML 0566, Cincinnati, OH 45206 USA. RP Cotton, S (reprint author), Univ Cincinnati, Dept Family & Community Med, Div Integrat Med, 231 Albert Sabin Way,ML 0566, Cincinnati, OH 45206 USA. EM sian.cotton@uc.edu OI Baas, Wesley/0000-0003-2542-8882 NR 15 TC 0 Z9 0 U1 2 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1933-6586 EI 1933-6594 J9 MED ACUPUNCT JI Med. Acupunct. PD JUN PY 2016 VL 28 IS 3 BP 131 EP 136 DI 10.1089/acu.2016.1170 PG 6 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA EB7MF UT WOS:000387571000003 ER PT J AU Yoshimi, N Futamura, T Kakumoto, K Salehi, AM Sellgren, CM Holmen-Larsson, J Jakobssong, J Palssong, E Landen, M Hashimoto, K AF Yoshimi, Noriko Futamura, Takashi Kakumoto, Keiji Salehi, Alireza M. Sellgren, Carl M. Holmen-Larsson, Jessica Jakobssong, Joel Palssong, Erik Landen, Mikael Hashimoto, Kenji TI Blood metabolomics analysis identifies abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism in bipolar disorder SO BBA CLINICAL LA English DT Article DE Bipolar disorder; Pyruvate; N-acetylglutamic acid; beta-alanine; Serine; Arginine ID MITOCHONDRIALLY MEDIATED PLASTICITY; ELECTROPHORESIS MASS-SPECTROMETRY; MAJOR DEPRESSIVE DISORDER; NEUROTROPHIC FACTOR BDNF; CEREBROSPINAL-FLUID; ARGININE METABOLISM; N-ACETYLGLUTAMATE; PRECURSOR PROBDNF; SERUM-LEVELS; D-SERINE AB Background: Bipolar disorder (BD) is a severe and debilitating psychiatric disorder. However, the precise biological basis remains unknown, hampering the search for novel biomarkers. We performed ametabolomics analysis to discover novel peripheral biomarkers for BD. Methods: We quantified serum levels of 116 metabolites inmood-stabilized male BD patients (n = 54) and age-matched male healthy controls (n = 39). Results: After multivariate logistic regression, serum levels of pyruvate, N-acetylglutamic acid, alpha-ketoglutarate, and arginine were significantly higher in BD patients than in healthy controls. Conversely, serum levels of beta-alanine, and serine were significantly lower in BD patients than in healthy controls. Chronic (4-weeks) administration of lithiumor valproic acid to adult male rats did not alter serum levels of pyruvate, N-acetylglutamic acid, beta-alanine, serine, or arginine, but lithium administration significantly increased serum levels of alpha-ketoglutarate. Conclusions: The metabolomics analysis demonstrated altered serum levels of pyruvate, N-acetylglutamic acid, beta-alanine, serine, and arginine in BD patients. General significance: The present findings suggest that abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism play a role in the pathogenesis of BD. (C) 2016 The Authors. Published by Elsevier B.V. C1 [Yoshimi, Noriko; Hashimoto, Kenji] Chiba Univ, Div Clin Neurosci, Ctr Forens Mental Hlth, 1-8-1 Inohana, Chiba 2608670, Japan. [Yoshimi, Noriko; Futamura, Takashi] Otsuka Pharmaceut Co Ltd, New Drug Res Div, Dept CNS Res, Tokushima, Japan. [Kakumoto, Keiji] Otsuka Pharmaceut Co Ltd, Tokushima Res Inst, Tokushima, Japan. [Salehi, Alireza M.] Karolinska Inst, Karolinska Univ Hosp Huddinge, Div Clin Chem, Dept Lab Med, Stockholm, Sweden. [Sellgren, Carl M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Sellgren, Carl M.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Holmen-Larsson, Jessica; Jakobssong, Joel; Palssong, Erik; Landen, Mikael] Univ Gothenburg, Inst Neurosci & Physiol, Sect Psychiat & Neurochem, Gothenburg, Sweden. [Landen, Mikael] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. RP Hashimoto, K (reprint author), Chiba Univ, Div Clin Neurosci, Ctr Forens Mental Hlth, 1-8-1 Inohana, Chiba 2608670, Japan. EM hashimoto@faculty.chiba-u.jp NR 67 TC 4 Z9 4 U1 7 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2214-6474 J9 BBA CLIN JI BBA Clin. PD JUN PY 2016 VL 5 BP 151 EP 158 DI 10.1016/j.bbacli.2016.03.008 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA EA8FA UT WOS:000386869500020 PM 27114925 ER PT J AU Spartano, NL Lyass, A Larson, MG Lewis, GD Vasan, RS AF Spartano, Nicole L. Lyass, Asya Larson, Martin G. Lewis, Gregory D. Vasan, Ramachandran S. TI Submaximal Exercise Systolic Blood Pressure and Heart Rate at 20 Years of Follow-up: Correlates in the Framingham Heart Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE aging; blood pressure; epidemiology; exercise; heart rate; risk factors ID MIDDLE-AGED MEN; ARTERIAL STIFFNESS; YOUNG-ADULTS; CARDIOVASCULAR MORTALITY; PHYSICAL-ACTIVITY; WEIGHT-GAIN; RISK; SMOKING; FITNESS; HYPERTENSION AB Background-Beyond their resting values, exercise responses in blood pressure (BP) and heart rate (HR) may add prognostic information for cardiovascular disease (CVD). In cross-sectional studies, exercise BP and HR responses correlate with CVD risk factors; however, it is unclear which factors influence longitudinal changes in exercise responses over time, which is important for our understanding of the development of CVD. Methods and Results-We assessed BP and HR responses to low-level exercise tests (6-minute Bruce protocol) in 1231 Framingham Offspring participants (55% women) who underwent a routine treadmill test in 1979-1983 (baseline; mean age 39 +/- 8 years) that was repeated in 1998-2001 (follow-up; mean age 58 +/- 8 years). Adjusting for baseline exercise responses, we related the follow-up exercise responses to baseline CVD risk factors and to their changes between examinations. Compared with men, women had greater rise in exercise systolic (S) BP and HR at 20-year follow-up (both P<0.005). Baseline blood lipid levels, resting SBP and HR, and smoking status were associated with greater exercise SBP at follow-up (all P<0.05). Weight gain across examinations was associated with higher exercise SBP and HR at follow-up (both P<0.0001). Smoking cessation was associated with a 53% reduced risk of attaining the highest quartile of exercise SBP (>= 180 mm Hg) at follow-up (P<0.05). Conclusion-An adverse CVD risk factor profile in young adults and its worsening over time were associated with higher SBP and HR responses to low-level exercise in midlife. Maintaining or adopting a healthy risk factor profile may favorably impact the exercise responses over time. C1 [Spartano, Nicole L.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Preventat Med & Epidemiol, Dept Med, Boston, MA 02118 USA. [Spartano, Nicole L.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Dept Med, Boston, MA 02118 USA. [Spartano, Nicole L.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Lyass, Asya; Larson, Martin G.; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Lyass, Asya; Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Lewis, Gregory D.] Harvard Med Sch, Massachusetts Gen Hosp, Div Cardiol, Cambridge, MA USA. [Lewis, Gregory D.] Harvard Med Sch, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA USA. [Lewis, Gregory D.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Vasan, Ramachandran S.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Spartano, NL (reprint author), Boston Univ, Sect Preventat Med & Epidemiol, 801 Massachusetts Ave,Suite 470, Boston, MA 02118 USA. EM spartano@bu.edu FU Framingham Heart Study's National Heart, Lung, and Blood Institute [N01-HC25195, HHSN268201500001I]; National Institutes of Health [R01-AG047645, R01-HL131029, T32-HL07224]; American Heart Association [15GPSGC24800006] FX This study was funded by the Framingham Heart Study's National Heart, Lung, and Blood Institute contract (N01-HC25195, HHSN268201500001I) with additional support from the following National Institutes of Health grants: (R01-AG047645, R01-HL131029, T32-HL07224) and American Heart Association award (15GPSGC24800006). NR 37 TC 0 Z9 0 U1 1 U2 1 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 JUN PY 2016 VL 5 IS 6 AR e002821 DI 10.1161/JAHA.115.002821 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EA6CK UT WOS:000386712700008 ER PT J AU Lofgreen, SJ Ashack, K Burton, KA Dellavalle, RP AF Lofgreen, Seth J. Ashack, Kurt Burton, Kyle A. Dellavalle, Robert P. TI Mobile Device Use in Dermatologic Patient Care SO CURRENT DERMATOLOGY REPORTS LA English DT Article DE Mobile phone patient care; Smartphones; Mobile apps; Applications teledermatology; Telemedicine; Teledermoscopy ID RANDOMIZED-CONTROLLED-TRIAL; FORWARD TELEDERMATOLOGY; HISTORICAL-PERSPECTIVE; EMERGING TECHNIQUES; TELEDERMOSCOPY; NEED; TECHNOLOGIES; SMARTPHONES; PHOTOGRAPHY; DERMOSCOPY AB Rapidly evolving technology, improved mobile device optics, and the uniquely visual nature of dermatology all promote mobile device use in the clinic. This paper examines how dermatologists use mobile device technology in direct patient care. We discuss mobile applications (apps) for both dermatologists and patients, as well as for integration with the electronic health record. Furthermore, we discuss aspects of teledermatology (including teledermoscopy), both from consults from a primary care provider and in using teledermatology to directly connect to the patient. Finally, we address patient perception of mobile devices in the clinic. C1 [Lofgreen, Seth J.] Univ Colorado, Denver Sch Med, Aurora, CO USA. [Ashack, Kurt] Michigan State Univ, Coll Human Med, Grand Rapids, MI USA. [Burton, Kyle A.] Univ Cent Florida, Coll Med, Orlando, FL 32816 USA. [Dellavalle, Robert P.] Univ Colorado, Dept Dermatol, Anschutz Med Campus, Aurora, CO 80045 USA. [Dellavalle, Robert P.] US Dept Vet Affairs, Med Ctr, Dermatol Serv, Eastern Colorado Hlth Care Syst, 1055 Clermont St,Box 165, Denver, CO 80220 USA. [Dellavalle, Robert P.] Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Anschutz Med Campus, Aurora, CO 80045 USA. RP Dellavalle, RP (reprint author), Univ Colorado, Dept Dermatol, Anschutz Med Campus, Aurora, CO 80045 USA.; Dellavalle, RP (reprint author), US Dept Vet Affairs, Med Ctr, Dermatol Serv, Eastern Colorado Hlth Care Syst, 1055 Clermont St,Box 165, Denver, CO 80220 USA.; Dellavalle, RP (reprint author), Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Anschutz Med Campus, Aurora, CO 80045 USA. EM robert.dellavalle@ucdenver.edu NR 39 TC 0 Z9 0 U1 3 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA EI 2162-4933 J9 CURR DERMATOL REP JI Curr. Dermatol. Rep. PD JUN PY 2016 VL 5 IS 2 BP 77 EP 82 DI 10.1007/s13671-016-0132-y PG 6 WC Dermatology SC Dermatology GA EA1ND UT WOS:000386358100002 ER PT J AU Foust-Wright, C Hudson, P Pulliam, S AF Foust-Wright, Caroline Hudson, Patricia Pulliam, Samantha TI Quality Measures for Prolapse Management SO CURRENT OBSTETRICS AND GYNECOLOGY REPORTS LA English DT Article DE Quality measures; Quality metrics; Pelvic organ prolapse; CMS incentives; Outcome measures ID PELVIC ORGAN PROLAPSE; URINARY-TRACT INJURY; FLOOR DISORDERS; OF-LIFE; UNIVERSAL CYSTOSCOPY; GYNECOLOGIC SURGERY; VAGINAL PROLAPSE; INCONTINENCE; OUTCOMES; PATIENT AB Quality measure development has become increasingly important over the past few years, and there have been many attempts to increase the scientific literature on the subject. Measurement of quality is now an integral part of the healthcare system. This review considers recently recommended quality metrics for prolapse management, subdividing these into structural, process, and outcome metrics. The Quality in Prolapse Surgery (QuIPS) project, Choosing Wisely (R) campaign by the American Board of Internal Medicine (ABIM), quality measures proposed by AUGS, and the 2012 joint report from IUGA and International Continence Society (ICS) are included this review. Evaluation of adherence to quality metrics is also discussed. C1 [Foust-Wright, Caroline] Massachusetts Gen Hosp, Dept Obstet & Gynecol, 55 Fruit St, Boston, MA 02114 USA. [Hudson, Patricia] Maine Med Ctr, Dept Obstet & Gynecol, 22 Bramhall St, Portland, ME 04102 USA. [Pulliam, Samantha] Univ N Carolina, Dept Obstet & Gynecol, 3032 Old Clin Bldg,CB 7570, Chapel Hill, NC 27599 USA. RP Pulliam, S (reprint author), Univ N Carolina, Dept Obstet & Gynecol, 3032 Old Clin Bldg,CB 7570, Chapel Hill, NC 27599 USA. EM Samantha_pulliam@med.unc.edu; c.foustwright@gmail.com; phudson@mmc.org NR 39 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 2161-3303 J9 CURR OBSTET GYNECOL JI CURR. OBSTET. GYNECOL. REP. PD JUN PY 2016 VL 5 IS 2 BP 152 EP 157 DI 10.1007/s13669-016-0160-4 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA EA0DD UT WOS:000386254800013 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI SHARING OUR KNOWLEDGE: The Tlingit and Their Coastal Neighbors SO JOURNAL OF THE WEST LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mifflin, Jeffrey] Harvard Sch Business, McLean Hosp, MIT, Boston, MA USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU ABC-CLIO PI SANTA BARBARA PA 130 CREMONA DR, SANTA BARBARA, CA 93117 USA SN 0022-5169 EI 1930-0115 J9 J WEST JI J. West PD SUM PY 2016 VL 55 IS 3 BP 76 EP 78 PG 3 WC History SC History GA EA1BM UT WOS:000386323300011 ER PT J AU Lewandrowski, K AF Lewandrowski, Kent TI Three Wishes for Point-of-Care Testing A Compendium of Unmet Needs From the Perspective of Practitioners in the Field SO POINT OF CARE LA English DT Article DE point-of-care testing; bedside testing; unmet needs; laboratory testing C1 [Lewandrowski, Kent] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lewandrowski, K (reprint author), Massachusetts Gen Hosp, Gray Chem 5, 55 Fruit St, Boston, MA 02114 USA. EM klewandrowski@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1533-029X EI 1533-0303 J9 POINT CARE JI Point Care PD JUN PY 2016 VL 15 IS 2 BP 78 EP 80 DI 10.1097/POC.0000000000000094 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA DZ8NO UT WOS:000386127300004 ER PT J AU Gregory, K AF Gregory, Kim TI Point-of-Care Testing The Future Is Now SO POINT OF CARE LA English DT Article DE vector; research; Office 365; innovation; rapid; tricorder; Star Trek AB Point of care testing needs to continue being the leader in new technologies. Corporate decisions, emerging infectious diseases and software/technology developments all contribute to the prospective agility of the POCT field. C1 [Gregory, Kim] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Gregory, K (reprint author), Massachusetts Gen Hosp, Pathol Serv, 55 Fruit St, Boston, MA 02114 USA. EM kgregory2@partners.org NR 0 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1533-029X EI 1533-0303 J9 POINT CARE JI Point Care PD JUN PY 2016 VL 15 IS 2 BP 89 EP 89 DI 10.1097/POC.0000000000000099 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA DZ8NO UT WOS:000386127300009 ER PT J AU Chang, HJ Kang, HM Ko, E Jun, BH Lee, HY Lee, YS Jeang, DH AF Chang, Hyejin Kang, Homan Ko, Eunbyeol Jun, Bong-Hyun Lee, Ho-Young Lee, Yoon-Sik Jeang, Dae Hong TI PSA Detection with Femtomolar Sensitivity and a Broad Dynamic Range Using SERS Nanoprobes and an Area-Scanning Method SO ACS SENSORS LA English DT Article DE surface-enhanced Raman scattering (SERS); immunoassay; prostate specific antigen (PSA); SERS nanoprobe; area-scanning ID ENHANCED RAMAN-SCATTERING; PROTEIN-DETECTION; IMMUNOASSAY; BIOMARKERS; ANTIGEN; LABELS; ASSAY AB Recently, surface-enhanced Raman scattering (SERS)-based immunoassays (SIA) have drawn much attention as diagnostic tools with large multiplex capacity and high sensitivity. However, several challenges-such as a low reproducibility, a time-consuming read-out process, and limited dynamic range-remain. In this study, we report a reliable and sensitive SIA platform for prostate specific antigen (PSA) detection. Reliability and sensitivity were achieved by two approaches: (1) well-established SERS probes, so-called SERS dots that have high sensitivity (single particle detection) and little particle-to-particle variation in SERS intensity; and (2) a whole area-scanning readout method for rapid and reliable chip analysis rather than point scanning. As a feasibility test, PSA could be detected with high sensitivity (ca. 0.11 pg/mL, 3.4 fM LOD), with a wide dynamic range (0.001-1000 ng/mL). Thus, the developed platform will facilitate development of reliable immunoassays with high sensitivity and a wide dynamic range. C1 [Chang, Hyejin; Ko, Eunbyeol; Jeang, Dae Hong] Seoul Natl Univ, Dept Chem Educ, Seoul 08826, South Korea. [Kang, Homan] Seoul Natl Univ, Interdisciplinary Program Nanosci & Technol, Seoul 08826, South Korea. [Lee, Yoon-Sik] Seoul Natl Univ, Sch Chem & Biol Engn, Seoul 08826, South Korea. [Jun, Bong-Hyun] Konkuk Univ, Dept Biosci & Biotechnol, Seoul 05029, South Korea. [Lee, Ho-Young] Seoul Natl Univ, Bundang Hosp, Dept Nucl Med, Songnam 13620, South Korea. [Kang, Homan] Harvard Med Sch, Dept Radiol, Boston, MA 02129 USA. [Kang, Homan] Massachusetts Gen Hosp, Gordon Ctr Med Imaging, Boston, MA 02129 USA. RP Jeang, DH (reprint author), Seoul Natl Univ, Dept Chem Educ, Seoul 08826, South Korea.; Lee, YS (reprint author), Seoul Natl Univ, Sch Chem & Biol Engn, Seoul 08826, South Korea.; Lee, HY (reprint author), Seoul Natl Univ, Bundang Hosp, Dept Nucl Med, Songnam 13620, South Korea. EM debobkr@gmail.com; yslee@snu.ac.kr; jeongdh@snu.ac.kr FU Pioneer Research Center Program through the National Research Foundation of Korea - Ministry of Science, ICT & Future Planning [2013-006163] FX This research was supported by the Pioneer Research Center Program through the National Research Foundation of Korea, funded by the Ministry of Science, ICT & Future Planning (Grant Number 2013-006163). NR 26 TC 4 Z9 4 U1 10 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 2379-3694 J9 ACS SENSORS JI ACS Sens. PD JUN PY 2016 VL 1 IS 6 BP 645 EP 649 DI 10.1021/acssensors.6b00053 PG 5 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Chemistry; Science & Technology - Other Topics GA DY9OX UT WOS:000385464800004 ER PT J AU Gutierrez, PM Davidson, CL Friese, AH Forster, JE AF Gutierrez, Peter M. Davidson, Collin L. Friese, Ariel H. Forster, Jeri E. TI Physical Activity, Suicide Risk Factors, and Suicidal Ideation in a Veteran Sample SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; HEART-RATE-VARIABILITY; COLLEGE-STUDENTS; SLEEP PROBLEMS; PUBLIC-HEALTH; EXERCISE; BEHAVIOR; DEPRESSION; ADULTS AB The association between current level of suicidal ideation and physical activity was tested in a broad sample of veterans seeking care from the Veterans Health Administration. It was hypothesized that the two variables would be significantly inversely related. It was further hypothesized that the relationship would be mediated by depressive symptoms, disturbed sleep, and a measure of heart rate variability based on existing research regarding physical activity and sleep. Due to the first hypothesis not being supported, the second could not be tested. Post hoc correlation analyses did find associations between physical activity and depressive symptoms, in expected directions, and are discussed. Possible explanations for the negative findings along with recommendations for future research to continue exploring links between suicide risk and physical activity are presented. We conclude by suggesting that physical activity may have promise as a risk reduction intervention and that prospective data are more likely to yield significant results than the cross-sectional methodology employed in the current study. C1 [Gutierrez, Peter M.] Denver VA Med Ctr, Rocky Mt Mental Illness Res Educ & Clin Ctr MIREC, 1055 Clermont St, Denver, CO 80220 USA. [Gutierrez, Peter M.] Univ Colorado, Sch Med, Dept Psychiat, Aurora, CO USA. [Davidson, Collin L.; Friese, Ariel H.; Forster, Jeri E.] Denver VA Med Ctr, Rocky Mt MIRECC, Denver, CO USA. [Forster, Jeri E.] Univ Colorado, Sch Med, Dept Phys Med & Rehabil, Aurora, CO USA. [Forster, Jeri E.] Colorado Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO USA. RP Gutierrez, PM (reprint author), Denver VA Med Ctr, Rocky Mt Mental Illness Res Educ & Clin Ctr MIREC, 1055 Clermont St, Denver, CO 80220 USA. EM peter.gutierrez@va.gov FU Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs FX This material is the result of work supported by the Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs. The expressed views do not necessarily represent those of the Department of Veterans Affairs or the U.S. Government. NR 42 TC 0 Z9 0 U1 8 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0363-0234 EI 1943-278X J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD JUN PY 2016 VL 46 IS 3 BP 284 EP 292 DI 10.1111/sltb.12190 PG 9 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DZ2XK UT WOS:000385705800003 PM 26404757 ER PT J AU Ricklefs, CA Asdigian, NL Kalra, HL Mayer, JA Dellavalle, RP Holman, DM Crane, LA AF Ricklefs, Christine A. Asdigian, Nancy L. Kalra, Heidi L. Mayer, Joni A. Dellavalle, Robert P. Holman, Dawn M. Crane, Lori A. TI Indoor tanning promotions on social media in six US cities #UVTanning #tanning SO TRANSLATIONAL BEHAVIORAL MEDICINE LA English DT Article DE Indoor tanning; Skin cancer; Social media; Advertising ID SKIN-CANCER; UNITED-STATES; MELANOMA; PREVALENCE; FACILITIES; COSTS; ADVERTISEMENTS; MORTALITY; EXPOSURE; BURDEN AB There is no research investigating indoor tanning advertising on social media. We assessed the use of social media to promote indoor tanning. We subscribed to social media platforms in six US cities and content-analyzed promotional messages received. We captured 662 messages on Twitter and Facebook, through salon emails, and in daily deal coupons. Salon postings were most frequent on Twitter and Facebook, with an average of 2-3 postings per week. National chains posted more frequently than local businesses. Forty percent of messages were devoid of tanning content and included photos, jokes, or popular references. Thirty percent mentioned price reductions, and 28 % referenced an upcoming holiday. Sunless tanning (17 %) was promoted more often than ultraviolet tanning (9 %). Tanning salons actively use social media as a strategy for maintaining relationships with customers and offer pricing deals that promote loyalty and high-frequency tanning. C1 [Ricklefs, Christine A.] Univ Colorado, Ctr Canc, Res Informat Shared Resource, Anschutz Med Campus, Aurora, CO USA. [Asdigian, Nancy L.; Crane, Lori A.] Univ Colorado, Dept Community & Behav Hlth, Colorado Sch Publ Hlth, Anschutz Med Campus,13001 E 17th Pl,B119, Aurora, CO 80045 USA. [Kalra, Heidi L.] Chatham Univ, Studies Program, Pittsburgh, PA USA. [Mayer, Joni A.] San Diego State Univ, Grad Sch Publ Hlth, Div Hlth Promot, San Diego, CA 92182 USA. [Dellavalle, Robert P.] Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Anschutz Med Campus, Aurora, CO USA. [Dellavalle, Robert P.] Univ Colorado, Sch Med, Dept Dermatol, Anschutz Med Campus, Aurora, CO USA. [Dellavalle, Robert P.] Dermatol Serv, Aurora, CO USA. [Dellavalle, Robert P.] Eastern Colorado Hlth Care Syst, US Dept Vet Affairs, Denver, CO USA. [Holman, Dawn M.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. RP Crane, LA (reprint author), Univ Colorado, Dept Community & Behav Hlth, Colorado Sch Publ Hlth, Anschutz Med Campus,13001 E 17th Pl,B119, Aurora, CO 80045 USA. EM lori.crane@ucdenver.edu FU Centers for Disease Control and Prevention, Division of Cancer Prevention and Control, Prevention Research Center [U48DP001938-0451] FX This research was supported by the Centers for Disease Control and Prevention, Division of Cancer Prevention and Control, Prevention Research Center grant number U48DP001938-0451 to Lori A. Crane. NR 43 TC 2 Z9 2 U1 4 U2 4 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1869-6716 EI 1613-9860 J9 TRANSL BEHAV MED JI Transl. Behav. Med. PD JUN PY 2016 VL 6 IS 2 BP 260 EP 270 DI 10.1007/s13142-015-0378-0 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DY6TL UT WOS:000385261100012 PM 27356996 ER PT J AU Zaina, F Donzelli, S French, MN Fregni, F AF Zaina, Fabio Donzelli, Sabrina French, Melanie N. Fregni, Felipe TI Ethics in rehabilitation: challenges and opportunities to promote research SO EUROPEAN JOURNAL OF PHYSICAL AND REHABILITATION MEDICINE LA English DT Editorial Material ID IMPACT FACTOR; MEDICINE C1 [Zaina, Fabio; Donzelli, Sabrina] Italian Sci Spine Inst ISICO, Via Roberto Bellarmino 13-1, I-20141 Milan, Italy. [French, Melanie N.; Fregni, Felipe] Spaulding Rehabil Hosp, Spaulding Neuromodulat Ctr, Boston, MA USA. [French, Melanie N.; Fregni, Felipe] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. RP Zaina, F (reprint author), Italian Sci Spine Inst ISICO, Via Roberto Bellarmino 13-1, I-20141 Milan, Italy. EM fabio.zaina@isico.it NR 7 TC 0 Z9 0 U1 0 U2 0 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 1973-9087 EI 1973-9095 J9 EUR J PHYS REHAB MED JI Eur. J. Phys. Rehabil. Med. PD JUN PY 2016 VL 52 IS 3 BP 267 EP 270 PG 4 WC Rehabilitation SC Rehabilitation GA DY2UD UT WOS:000384946700001 PM 27225193 ER PT J AU Schapira, MM Shea, JA Duey, KA Kleiman, C Werner, RM AF Schapira, Marilyn M. Shea, Judy A. Duey, Katia A. Kleiman, Carly Werner, Rachel M. TI The Nursing Home Compare Report Card: Perceptions of Residents and Caregivers Regarding Quality Ratings and Nursing Home Choice SO HEALTH SERVICES RESEARCH LA English DT Article DE Nursing home; public reporting; quality indicators ID INFORMATION; CONSUMERS; DISPARITIES AB Objective. To evaluate the perceived usefulness of publicly reported nursing home quality indicators. Study Setting. Primary data were collected from October 2013 to August 2014 among a convenience sample of persons (or family member) recently admitted or anticipating admission to a nursing home within 75 miles of the city of Philadelphia. Study Design. Structured interviews were conducted to assess the salience of data on the Medicare Nursing Home Compare website, including star ratings, clinical quality measures, and benchmarking of individual nursing home quality with state and national data. Data Collection. Interviews were transcribed verbatim, independently coded by two reviewers, and agreement determined. A thematic analysis of transcripts was undertaken. Principal Findings. Thirty-five interviews were completed. Eighty-three percent (n = 29) were caregivers and 17 percent (n = 6) were residents. Star ratings, clinical quality measures, and benchmarking information were salient to decision making, with preferred formats varying across participants. Participants desired additional information on the source of quality data. Confusion was evident regarding the relationship between domain-specific and overall star quality ratings. Conclusions. The Nursing Home Compare website provides salient content and formats for consumers. Increased awareness of this resource and clarity regarding the definition of measures could further support informed decision making regarding nursing home choice. C1 [Schapira, Marilyn M.; Shea, Judy A.; Duey, Katia A.; Kleiman, Carly; Werner, Rachel M.] Univ Penn, Perelman Sch Med, Div Gen Med, 1110 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. [Schapira, Marilyn M.] VAMC, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Shea, Judy A.; Werner, Rachel M.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Werner, Rachel M.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Schapira, MM (reprint author), Univ Penn, Perelman Sch Med, Div Gen Med, 1110 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM mschap@upenn.edu FU Agency for Healthcare Research and Quality (AHRQ) [R21HS02861]; NIA [K24-AG047908] FX This study was supported by a grant from the Agency for Healthcare Research and Quality (AHRQ) R21HS02861. This study also acknowledges support for Dr. Werner from the NIA (K24-AG047908). There was no requirement from the funder to review work prior to submission. NR 26 TC 1 Z9 1 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 EI 1475-6773 J9 HEALTH SERV RES JI Health Serv. Res. PD JUN PY 2016 VL 51 SU 2 BP 1212 EP 1228 DI 10.1111/1475-6773.12458 PG 17 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DX9UY UT WOS:000384743500004 PM 26867949 ER PT J AU Werner, RM Konetzka, RT Polsky, D AF Werner, Rachel M. Konetzka, R. Tamara Polsky, Daniel TI Changes in Consumer Demand Following Public Reporting of Summary Quality Ratings: An Evaluation in Nursing Homes SO HEALTH SERVICES RESEARCH LA English DT Article DE Quality of care; public reporting; quality measures; nursing home ID REPORT CARDS; PERFORMANCE DATA; OF-CARE; INFORMATION; CHOICE; MARKET AB Objective. Limited consumer use of health care report cards may be due to the large amount of information presented in report cards, which can be difficult to understand. These limitations may be overcome with summary measures. Our objective was to evaluate consumer response to summary measures in the setting of nursing homes. Data Sources/Study Setting. 2005-2010 nursing home Minimum Data Set and Online Survey, Certification and Reporting (OSCAR) datasets. Study Design. In December 2008, Medicare converted its nursing home report card to summary or star ratings. We test whether there was a change in consumer demand for nursing homes related to the nursing home's star rating after the information was released. Principal Findings. The star rating system was associated with a significant change in consumer demand for low-and high-scoring facilities. After the star-based rating system was released, 1-star facilities typically lost 8 percent of their market share and 5-star facilities gained over 6 percent of their market share. Conclusions. The nursing home star rating system significantly affected consumer demand for high-and low-rated nursing homes. These results support the use of summary measures in report cards. C1 [Werner, Rachel M.; Polsky, Daniel] Univ Penn, Perelman Sch Med, Div Gen Internal Med, 1204 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. [Werner, Rachel M.] Philadelphia VAMC, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Werner, Rachel M.; Polsky, Daniel] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Konetzka, R. Tamara] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. RP Werner, RM (reprint author), Univ Penn, Perelman Sch Med, Div Gen Internal Med, 1204 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rwerner@upenn.edu FU Agency for Healthcare Research and Quality [R21-HS021861]; National Institute on Aging [K24-AG047908] FX This research was supported by grant number R21-HS021861 from the Agency for Healthcare Research and Quality. Rachel Werner was supported in part by grant number K24-AG047908 from the National Institute on Aging. We gratefully thank Chris Wirtalla for his help with data management and programming. NR 31 TC 2 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 EI 1475-6773 J9 HEALTH SERV RES JI Health Serv. Res. PD JUN PY 2016 VL 51 SU 2 BP 1291 EP 1309 DI 10.1111/1475-6773.12459 PG 19 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DX9UY UT WOS:000384743500008 PM 26868034 ER PT J AU Pomerleau, M AF Pomerleau, Mimi TI Engaging Front Line Nurses to Examine Evidence for Practice With Integrative Review Methodology SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING LA English DT Meeting Abstract DE integrative review; pacifiers; team based C1 [Pomerleau, Mimi] Massachusetts Gen Hosp, Inst Hlth Profess, Reading, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0884-2175 EI 1552-6909 J9 JOGNN-J OBST GYN NEO JI JOGNN PD JUN PY 2016 VL 45 IS 3 SU S BP S36 EP S36 PG 1 WC Nursing; Obstetrics & Gynecology SC Nursing; Obstetrics & Gynecology GA DY3NH UT WOS:000385000000073 ER PT J AU Ma, D Pierre, EY Jiang, Y Schluchter, MD Setsompop, K Gulani, V Griswold, MA AF Ma, Dan Pierre, Eric Y. Jiang, Yun Schluchter, Mark D. Setsompop, Kawin Gulani, Vikas Griswold, Mark A. TI Music-Based Magnetic Resonance Fingerprinting to Improve Patient Comfort During MRI Examinations SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE magnetic resonance fingerprinting; quantitative imaging; relaxation time; music ID ACOUSTIC NOISE; STEADY-STATE; GRADIENT COILS; HUMAN BRAIN; RECONSTRUCTION; STRATEGIES; EXCITATION; GRAPPA AB Purpose: Unpleasant acoustic noise is a drawback of almost every MRI scan. Instead of reducing acoustic noise to improve patient comfort, we propose a technique for mitigating the noise problem by producing musical sounds directly from the switching magnetic fields while simultaneously quantifying multiple important tissue properties. Theory and Methods: MP3 music files were converted to arbitrary encoding gradients, which were then used with varying flip angles and repetition times in a two-and three-dimensional magnetic resonance fingerprinting (MRF) examination. This new acquisition method, named MRF-Music, was used to quantify T-1, T-2, and proton density maps simultaneously while providing pleasing sounds to the patients. Results: MRF-Music scans improved patient comfort significantly during MRI examinations. The T-1 and T-2 values measured from phantom are in good agreement with those from the standard spin echo measurements. T-1 and T-2 values from the brain scan are also close to previously reported values. Conclusions: MRF-Music sequence provides significant improvement in patient comfort compared with the MRF scan and other fast imaging techniques such as echo planar imaging and turbo spin echo scans. It is also a fast and accurate quantitative method that quantifies multiple relaxation parameters simultaneously. (C) 2015 Wiley Periodicals, Inc. C1 [Ma, Dan; Pierre, Eric Y.; Jiang, Yun; Gulani, Vikas; Griswold, Mark A.] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. [Schluchter, Mark D.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Setsompop, Kawin] Harvard Med Sch, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Boston, MA USA. [Gulani, Vikas; Griswold, Mark A.] Case Western Reserve Univ, Dept Radiol, Cleveland, OH 44106 USA. RP Griswold, MA (reprint author), Case Western Reserve Univ, 11100 Euclid Ave,Bolwell B121, Cleveland, OH 44106 USA. EM mark.griswold@case.edu OI Pierre, Eric/0000-0002-3196-5417 FU National Institutes of Health [1R01-EB016728-01A1, 5R01-EB017219-02]; Siemens Healthcare FX Grant sponsor: National Institutes of Health; Grant number: 1R01-EB016728-01A1 and 5R01-EB017219-02; Grant sponsor: Siemens Healthcare. NR 39 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD JUN PY 2016 VL 75 IS 6 BP 2303 EP 2314 DI 10.1002/mrm.25818 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DY3LS UT WOS:000384994700009 ER PT J AU Martin, A Schiavi, E Eryaman, Y Herraiz, JL Gagoski, B Adalsteinsson, E Wald, LL Guerin, B AF Martin, Adrian Schiavi, Emanuele Eryaman, Yigitcan Herraiz, Joaquin L. Gagoski, Borjan Adalsteinsson, Elfar Wald, Lawrence L. Guerin, Bastien TI Parallel Transmission Pulse Design with Explicit Control for the Specific Absorption Rate in the Presence of Radiofrequency Errors SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE pTx pulse design; SAR control; RF errors; high-field MRI ID LEAST-SQUARES OPTIMIZATION; RF PULSES; CARTESIAN FEEDBACK; SAR REDUCTION; 8 CHANNELS; HIGH-FIELD; LOCAL SAR; BODY MRI; EXCITATION; POWER AB Purpose: A new framework for the design of parallel transmit (pTx) pulses is presented introducing constraints for local and global specific absorption rate (SAR) in the presence of errors in the radiofrequency (RF) transmit chain. Methods: The first step is the design of a pTx RF pulse with explicit constraints for global and local SAR. Then, the worst possible SAR associated with that pulse due to RF transmission errors ("worst-case SAR") is calculated. Finally, this information is used to re-calculate the pulse with lower SAR constraints, iterating this procedure until its worst-case SAR is within safety limits. Results: Analysis of an actual pTx RF transmit chain revealed amplitude errors as high as 8% (20%) and phase errors above 3 degrees (15 degrees) for spokes (spiral) pulses. Simulations show that using the proposed framework, pulses can be designed with controlled "worst-case SAR" in the presence of errors of this magnitude at minor cost of the excitation profile quality. Conclusion: Our worst-case SAR-constrained pTx design strategy yields pulses with local and global SAR within the safety limits even in the presence of RF transmission errors. This strategy is a natural way to incorporate SAR safety factors in the design of pTx pulses. (C) 2015 Wiley Periodicals, Inc. C1 [Martin, Adrian; Schiavi, Emanuele] Univ Rey Juan Carlos, Appl Math, Madrid, Spain. [Martin, Adrian; Adalsteinsson, Elfar] MIT, Elect Engn & Comp Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Eryaman, Yigitcan; Wald, Lawrence L.; Guerin, Bastien] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Eryaman, Yigitcan; Herraiz, Joaquin L.] MIT, Madrid MIT M Vis Consortium RLE, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Gagoski, Borjan] Harvard Med Sch, Boston Childrens Hosp, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA USA. [Adalsteinsson, Elfar] MIT, Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Adalsteinsson, Elfar; Wald, Lawrence L.] MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RP Martin, A (reprint author), Univ Rey Juan Carlos, Dept 2, Calle Tulipan S-N,Despacho 021, Madrid 28933, Spain. EM adrian.martin@urjc.es RI Martin Fernandez, Adrian/H-7802-2015; LOPEZ HERRAIZ, JOAQUIN/E-9234-2010 OI Martin Fernandez, Adrian/0000-0001-7127-0073; LOPEZ HERRAIZ, JOAQUIN/0000-0001-7208-8863 FU Consejeria de Educacion, Juventud y Deporte de la Comunidad de Madrid (Spain) through Madrid-MIT M | Vision Consortium project; Spanish Ministry of Economy and Competitiveness [TEC2012-39095-C03-02]; National Institutes of Health [R01EB006847]; Siemens-MIT CKI Alliance FX Grant sponsor: Consejeria de Educacion, Juventud y Deporte de la Comunidad de Madrid (Spain) through the Madrid-MIT M | Vision Consortium project; Grant sponsor: Spanish Ministry of Economy and Competitiveness; Grant number: Project TEC2012-39095-C03-02; Grant sponsor: National Institutes of Health; Grant number: R01EB006847; Grant sponsor: Siemens-MIT CKI Alliance. NR 45 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD JUN PY 2016 VL 75 IS 6 BP 2493 EP 2504 DI 10.1002/mrm.25820 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DY3LS UT WOS:000384994700029 PM 26147916 ER PT J AU Nierenberg, AA AF Nierenberg, Andrew A. TI The Psychiatrist's Role in Transgender Mental Health SO PSYCHIATRIC ANNALS LA English DT Editorial Material C1 [Nierenberg, Andrew A.] Massachusetts Gen Hosp, MGH Res Inst, Psychiat, Boston, MA 02114 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, MGH Res Inst, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, MGH Res Inst, Training & Educ, Boston, MA 02114 USA. [Nierenberg, Andrew A.] Harvard Med Sch, Psychiat, Boston, MA 02115 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, MGH Res Inst, Psychiat, Boston, MA 02114 USA.; Nierenberg, AA (reprint author), Massachusetts Gen Hosp, MGH Res Inst, Bipolar Clin & Res Program, Boston, MA 02114 USA.; Nierenberg, AA (reprint author), Massachusetts Gen Hosp, MGH Res Inst, Training & Educ, Boston, MA 02114 USA.; Nierenberg, AA (reprint author), Harvard Med Sch, Psychiat, Boston, MA 02115 USA. EM psyann@Healio.com NR 5 TC 0 Z9 0 U1 2 U2 2 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 JUN PY 2016 VL 46 IS 6 BP 324 EP 325 DI 10.3928/00485713-20160426-01 PG 2 WC Psychiatry SC Psychiatry GA DY3VD UT WOS:000385022300001 ER PT J AU Makarov, DV Hu, EYC Walter, D Braithwaite, RS Sherman, S Gold, HT Zhou, XHA Gross, CP Zeliadt, SB AF Makarov, Danil V. Hu, Elaine Y. C. Walter, Dawn Braithwaite, R. Scott Sherman, Scott Gold, Heather T. Zhou, Xiao-Hua Andrew Gross, Cary P. Zeliadt, Steven B. TI Appropriateness of Prostate Cancer Imaging among Veterans in a Delivery System without Incentives for Overutilization SO HEALTH SERVICES RESEARCH LA English DT Article DE Health care organizations and systems; VA health care system; surgery ID HOSPITAL VOLUME; UNITED-STATES; OF-LIFE; CARE; SURGERY; QUALITY; TRENDS; SURVIVAL; STAGE; MEN AB Objective. To determine the frequency of appropriate and inappropriate prostate cancer imaging in an integrated health care system. Data Sources/Study Setting. Veterans Health Administration Central Cancer Registry linked to VA electronic medical records and Medicare claims (2004-2008). Study Design. We performed a retrospective cohort study of VA patients diagnosed with prostate cancer (N = 45,084). Imaging (CT, MRI, bone scan, PET) use was assessed among patients with low-risk disease, for whom guidelines recommend against advanced imaging, and among high-risk patients for whom guidelines recommend it. Principal Findings. We found high rates of inappropriate imaging among men with low-risk prostate cancer (41 percent) and suboptimal rates of appropriate imaging among men with high-risk disease (70 percent). Veterans utilizing Medicare-reimbursed care had higher rates of inappropriate imaging [OR: 1.09 (1.03-1.16)] but not higher rates of appropriate imaging. Veterans treated in middle [OR: 0.51 (0.47-0.56)] and higher [OR: 0.50 (0.46-0.55)] volume medical centers were less likely to undergo inappropriate imaging without compromising appropriate imaging. Conclusions. Our results highlight the overutilization of imaging, even in an integrated health care system without financial incentives encouraging provision of health care services. Paradoxically, imaging remains underutilized among high-risk patients who could potentially benefit from it most. C1 [Makarov, Danil V.] 550 First Ave,VZ30 Sixth Floor,Off 613, New York, NY 10016 USA. [Makarov, Danil V.; Walter, Dawn; Sherman, Scott] VA New York Harbor Healthcare Syst, New York, NY USA. [Makarov, Danil V.] NYU, Robert Wagner Grad Sch Publ Serv, Dept Urol, New York, NY USA. [Makarov, Danil V.] NYU, Robert Wagner Grad Sch Publ Serv, Dept Populat Hlth, New York, NY USA. [Makarov, Danil V.] NYU, Robert Wagner Grad Sch Publ Serv, Inst Canc, New York, NY USA. [Hu, Elaine Y. C.; Zhou, Xiao-Hua Andrew; Zeliadt, Steven B.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Hu, Elaine Y. C.; Zhou, Xiao-Hua Andrew; Zeliadt, Steven B.] Univ Washington, Seattle, WA 98195 USA. [Walter, Dawn] NYU, Dept Urol, New York, NY USA. [Walter, Dawn] NYU, Dept Populat Hlth, New York, NY USA. [Walter, Dawn] NYU, Inst Canc, New York, NY USA. [Braithwaite, R. Scott; Sherman, Scott; Gold, Heather T.] NYU, Inst Canc, Populat Hlth, New York, NY USA. [Gross, Cary P.] Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT USA. [Gross, Cary P.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. RP Makarov, DV (reprint author), 550 First Ave,VZ30 Sixth Floor,Off 613, New York, NY 10016 USA.; Makarov, DV (reprint author), NYU, Robert Wagner Grad Sch Publ Serv, Dept Urol, New York, NY USA.; Makarov, DV (reprint author), NYU, Robert Wagner Grad Sch Publ Serv, Dept Populat Hlth, New York, NY USA.; Makarov, DV (reprint author), NYU, Robert Wagner Grad Sch Publ Serv, Inst Canc, New York, NY USA. EM danil.makarov@nyumc.org OI Makarov, Danil/0000-0002-0565-9272; Sherman, Scott/0000-0003-1752-7303 FU United States Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [CDA 11-257/Makarov CDP 12/254/Makarov, IIR 07-235/Zhou]; Louis Feil Charitable Lead Trust; Medtronic; Johnson Johnson; 21st Century Oncology FX The authors acknowledge the following funding sources: United States Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (CDA 11-257/Makarov CDP 12/254/Makarov "Optimizing Imaging Use Among Veterans with Prostate Cancer" and IIR 07-235/Zhou "Modeling of Health Care Costs (MHCC) of Veterans with Chronic Diseases"), and the Louis Feil Charitable Lead Trust. Dr. Makarov is a consultant for Castlight Health, LLC and for the United States Food and Drug Administration; Dr. Gross receives research support from Medtronic, Johnson & Johnson, and 21st Century Oncology. The views expressed in this article are those of the author(s) and do not necessarily represent the views of the Department of Veterans Affairs. NR 61 TC 2 Z9 2 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 EI 1475-6773 J9 HEALTH SERV RES JI Health Serv. Res. PD JUN PY 2016 VL 51 IS 3 BP 1021 EP 1051 DI 10.1111/1475-6773.12395 PG 31 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DX9UN UT WOS:000384741900010 PM 26423687 ER PT J AU Song, MY Hu, FB Spiegelman, D Chan, AT Wu, K Ogino, S Fuchs, CS Willett, WC Giovannucci, EL AF Song, Mingyang Hu, Frank B. Spiegelman, Donna Chan, Andrew T. Wu, Kana Ogino, Shuji Fuchs, Charles S. Willett, Walter C. Giovannucci, Edward L. TI Long-term status and change of body fat distribution, and risk of colorectal cancer: a prospective cohort study SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Body fat distribution; sex difference; postmenopausal hormone therapy ID COLON-CANCER; MASS INDEX; PHYSICAL-ACTIVITY; POSTMENOPAUSAL WOMEN; RECTAL-CANCER; ABDOMINAL ADIPOSITY; WAIST CIRCUMFERENCE; METABOLIC SYNDROME; WEIGHT CHANGE; SEX-HORMONES AB Background: Although obesity has been linked to an increased risk of colorectal cancer (CRC), the risk associated with long-term status or change of body fat distribution has not been fully elucidated. Methods: Using repeated anthropometric assessments in the Nurses' Health Study and Health Professionals Follow-up Study, we prospectively investigated cumulative average waist circumference, hip circumference and waist-to-hip ratio, as well as their 10-year changes over adulthood, in relation to CRC risk over 23-24 years of follow-up. Cox proportional hazards models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI). Results: High waist circumference, hip circumference and waist-to-hip ratio were all associated with a higher CRC risk in men, even after adjusting for body mass index. The association was attenuated to null in women after adjusting for body mass index. Ten-year gain of waist circumference was positively associated with CRC risk in men (P for trend = 0.03), but not in women (P for trend = 0.34). Compared with men maintaining their waist circumference, those gaining waist circumference by = 10 cm were at a higher risk of CRC, with a multivariable-adjusted HR of 1.59 (95% CI, 1.01-2.49). This association appeared to be independent of weight change. Conclusions: Abdominal adiposity, independent of overall obesity, is associated with an increased CRC risk in men but not in women. Our findings also provide the first prospective evidence that waist circumference gain during adulthood may be associated with higher CRC risk in men, thus highlighting the importance of maintaining a healthy waist for CRC prevention. C1 [Song, Mingyang; Hu, Frank B.; Spiegelman, Donna; Wu, Kana; Willett, Walter C.; Giovannucci, Edward L.] Harvard TH ChanSch Publ Hlth, Dept Nutr, Boston, MA USA. [Song, Mingyang; Hu, Frank B.; Spiegelman, Donna; Ogino, Shuji; Willett, Walter C.; Giovannucci, Edward L.] Harvard TH ChanSch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Hu, Frank B.; Chan, Andrew T.; Ogino, Shuji; Fuchs, Charles S.; Willett, Walter C.; Giovannucci, Edward L.] Harvard Med Sch, Channing Div Network Med, Boston, MA USA. [Spiegelman, Donna] Harvard TH ChanSch Publ Hlth, Dept Biostat, Boston, MA USA. [Spiegelman, Donna] Harvard TH ChanSch Publ Hlth, Dept Global Hlth & Populat, Boston, MA USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Ogino, Shuji; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Med Sch, Boston, MA USA. RP Song, MY (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Nutr, 655 Huntington Ave, Boston, MA 02115 USA.; Song, MY (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, 655 Huntington Ave, Boston, MA 02115 USA. EM msong@hsph.harvard.edu FU National Institutes of Health [UM1 CA186107, P01 CA87969, UM1 CA167552, P50 CA127003, R01 CA137178, R01 CA151993, R35 CA197735, K24 DK 098311, K07 CA190673, 1U54CA155626]; Agrusa Fund for Colorectal Cancer Research FX This work was supported by the National Institutes of Health [UM1 CA186107, P01 CA87969, UM1 CA167552, P50 CA127003, R01 CA137178, R01 CA151993, R35 CA197735, K24 DK 098311, K07 CA190673 and 1U54CA155626] and by a grant from the Agrusa Fund for Colorectal Cancer Research. The funders had no role in: design or conduct of the study; collection, management, analysis or interpretation of the data; preparation, review or approval of the manuscript; or the decision to submit the manuscript for publication. NR 51 TC 2 Z9 2 U1 2 U2 2 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 JUN PY 2016 VL 45 IS 3 BP 871 EP 883 DI 10.1093/ije/dyv177 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DX8QG UT WOS:000384653200040 PM 26403814 ER PT J AU Tsai, TY Dimitriou, D Li, JS Kwon, YM AF Tsai, Tsung-Yuan Dimitriou, Dimitris Li, Jing-Sheng Kwon, Young-Min TI Does haptic robot-assisted total hip arthroplasty better restore native acetabular and femoral anatomy? SO INTERNATIONAL JOURNAL OF MEDICAL ROBOTICS AND COMPUTER ASSISTED SURGERY LA English DT Article DE total hip arthroplasty; robot-assisted surgery; component positioning ID COMPUTER NAVIGATION; REPLACEMENT; COMPONENT; CUP; ORIENTATION; PLACEMENT; IMPINGEMENT; MOTION; RANGE; THA AB Background The objective was to evaluate whether total hip arthroplasty (THA) using haptic robot assistance restores hip geometry better than the free-hand technique. Methods Twelve robot-assisted and 14 free-hand unilateral THA patients underwent CT scan for three-dimensional (3D) hip models. The anteversion, inclination and hip joint centre locations of the native and implanted hips in each patient were quantified and compared. Results Significant increase of combined anteversion by 19.1 +/- 11.7 degrees and 23.5 +/- 23.6 degrees and decrease of cup inclination by 16.5 +/- 6.0 degrees and 10.2 +/- 6.8 degrees were observed in the robot-assisted and the free-hand THAs, respectively. Less variation in the difference of the component orientations (max 11.1 vs 18.3 degrees) and the femoral head centre (max 4.5 vs 6.3mm) were found in the robot-assisted group. Conclusion This study demonstrated that neither robot-assisted nor free-hand THAs had fully restored native hip geometry. However, the higher precision of the robot-assisted THA suggested that it has potential utility in restoring the native hip geometry. Copyright (C) 2015 John Wiley & Sons, Ltd. C1 [Tsai, Tsung-Yuan; Dimitriou, Dimitris; Li, Jing-Sheng; Kwon, Young-Min] Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthoped Surg, 55 Fruit St, Boston, MA 02114 USA. RP Kwon, YM (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthoped Surg, 55 Fruit St, Boston, MA 02114 USA. EM ymkwon@mgh.harvard.edu OI Tsai, Tsung-Yuan/0000-0003-1522-2987; Dimitriou, Dimitris/0000-0002-9558-7080 FU MAKO Surgical Corp. FX This work has been partially funded by MAKO Surgical Corp. NR 26 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1478-5951 EI 1478-596X J9 INT J MED ROBOT COMP JI Int. J. Med. Robot. Comput. Assist. Surg. PD JUN PY 2016 VL 12 IS 2 BP 288 EP 295 DI 10.1002/rcs.1663 PG 8 WC Surgery SC Surgery GA DY1FO UT WOS:000384840500014 PM 25906764 ER PT J AU Speier, W Ong, MK Arnold, CW AF Speier, William Ong, Michael K. Arnold, Corey W. TI Using phrases and document metadata to improve topic modeling of clinical reports SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE Topic modeling; LDA; n-grams; Document metadata ID INFORMATION AB Probabilistic topic models provide an unsupervised method for analyzing unstructured text, which have the potential to be integrated into clinical automatic summarization systems. Clinical documents are accompanied by metadata in a patient's medical history and frequently contains multiword concepts that can be valuable for accurately interpreting the included text. While existing methods have attempted to address these problems individually, we present a unified model for free-text clinical documents that integrates contextual patient- and document-level data, and discovers multi-word concepts. In the proposed model, phrases are represented by chained n-grams and a Dirichlet hyper-parameter is weighted by both document-level and patient-level context. This method and three other Latent Dirichlet allocation models were fit to a large collection of clinical reports. Examples of resulting topics demonstrate the results of the new model and the quality of the representations are evaluated using empirical log likelihood. The proposed model was able to create informative prior probabilities based on patient and document information, and captured phrases that represented various clinical concepts. The representation using the proposed model had a significantly higher empirical log likelihood than the compared methods. Integrating document metadata and capturing phrases in clinical text greatly improves the topic representation of clinical documents. The resulting clinically informative topics may effectively serve as the basis for an automatic summarization system for clinical reports. (C) 2016 Elsevier Inc. All rights reserved. C1 [Speier, William; Arnold, Corey W.] Univ Calif Los Angeles, Med Imaging Informat, Los Angeles, CA 90095 USA. [Ong, Michael K.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Ong, Michael K.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Arnold, Corey W.] Univ Calif Los Angeles, Dept Radiol Sci, Los Angeles, CA 90024 USA. [Speier, William] 924 Westwood Blvd Ste 420, Los Angeles, CA 90024 USA. RP Arnold, CW (reprint author), Univ Calif Los Angeles, Med Imaging Informat, Los Angeles, CA 90095 USA. EM speier@ucla.edu; cwarnold@ucla.edu FU National Library of Medicine of the National Institutes of Health [R21LM011937] FX This work was supported by a grant from the National Library of Medicine of the National Institutes of Health under award number R21LM011937 (PI Arnold). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 43 TC 1 Z9 1 U1 2 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 EI 1532-0480 J9 J BIOMED INFORM JI J. Biomed. Inform. PD JUN PY 2016 VL 61 BP 260 EP 266 DI 10.1016/j.jbi.2016.04.005 PG 7 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA DX9HN UT WOS:000384704300026 PM 27109931 ER PT J AU Lindau, ST Abramsohn, EM Carpenter, K Carter, J Faubion, S Feltmate, C Flynn, K Haseotes, D Jeffery, D Jhingran, A Joslin, I Kennedy, V Kushner, D Lynn, M Mumby, P AF Lindau, S. T. Abramsohn, E. M. Carpenter, K. Carter, J. Faubion, S. Feltmate, C. Flynn, K. Haseotes, D. Jeffery, D. Jhingran, A. Joslin, I Kennedy, V Kushner, D. Lynn, M. Mumby, P. TI DEVELOPMENT OF A HARMONIZED MULTI-SITE, PROSPECTIVE RESEARCH REGISTRY TO ACCELERATE EVIDENCE-BASED TREATMENT OF SEXUAL DISORDERS IN WOMEN AND GIRLS WITH CANCER SO JOURNAL OF SEXUAL MEDICINE LA English DT Meeting Abstract C1 [Lindau, S. T.; Abramsohn, E. M.; Joslin, I] Univ Chicago, Chicago, IL 60637 USA. [Carpenter, K.] Ohio State Univ, Columbus, OH 43210 USA. [Carter, J.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Faubion, S.] Mayo Clin, Rochester, MN USA. [Feltmate, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Flynn, K.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Haseotes, D.] Brown Univ, Providence, RI 02912 USA. [Jeffery, D.] US Dept Def, Washington, DC 20305 USA. [Jhingran, A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kennedy, V] Univ Calif Davis, Davis, CA 95616 USA. [Kushner, D.] Univ Wisconsin, Madison, WI 53706 USA. [Lynn, M.; Mumby, P.] Loyola Univ, Med Ctr, New Orleans, LA 70118 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 1743-6095 EI 1743-6109 J9 J SEX MED JI J. Sex. Med. PD JUN PY 2016 VL 13 IS 6 SU S MA 052 BP S261 EP S261 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA DX9SE UT WOS:000384734600050 ER PT J AU Knight, EM Kim, SH Kottwitz, JC Hatami, A Albay, R Suzuki, A Lublin, A Alberini, CM Klein, WL Szabo, P Relkin, NR Ehrlich, M Glabe, CG Gandy, S Steele, JW AF Knight, Elysse M. Kim, Soong Ho Kottwitz, Jessica C. Hatami, Asa Albay, Ricardo Suzuki, Akinobu Lublin, Alex Alberini, Cristina M. Klein, William L. Szabo, Paul Relkin, Norman R. Ehrlich, Michelle Glabe, Charles G. Gandy, Sam Steele, John W. TI Effective anti-Alzheimer A beta therapy involves depletion of specific A beta oligomer subtypes SO NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION LA English DT Article ID HUMAN INTRAVENOUS IMMUNOGLOBULIN; AMYLOID-BETA; MOUSE MODEL; MONOCLONAL-ANTIBODIES; DISEASE BRAIN; IN-VITRO; PEPTIDE; PATHOLOGY; MICE; DYSFUNCTION AB Background: Recent studies have implicated specific assembly subtypes of \-amyloid (A beta) peptide, specifically soluble oligomers (soA beta) as disease-relevant structures that may underlie memory loss in Alzheimer disease. Removing existing soluble and insoluble A beta assemblies is thought to be essential for any attempt at stabilizing brain function and slowing cognitive decline in Alzheimer disease. IV immunoglobulin (IVIg) therapies have been shown to contain naturally occurring polyclonal antibodies that recognize conformational neoepitopes of soluble or insoluble A beta assemblies including soA beta. These naturally occurring polyclonal antibodies have been suggested to underlie the apparent clinical benefits of IVIg. However, direct evidence linking anti-A beta antibodies to the clinical bioactivity of IVIg has been lacking. Methods: Five-month-old female Dutch APP E693Q mice were treated for 3 months with neat IVIg or with IVIg that had been affinity-depleted over immobilized A beta conformers in 1 of 2 assembly states. Memory was assessed in a battery of tests followed by quantification of brain soA beta levels using standard anti-soA beta antibodies. Results: We provide evidence that NU4-type soA beta (NU4-soA beta) assemblies accumulate in the brains of Dutch APP E693Q mice and are associated with defects in memory, even in the absence of insoluble A beta plaques. Memory benefits were associated with depletion from APP E693Q mouse brain of NU4-soA beta and A11-soA beta but not OC-type fibrillar A beta oligomers. Conclusions: We propose that targeting of specific soA beta assembly subtypes may be an important consideration in the therapeutic and/or prophylactic benefit of anti-A beta antibody drugs. C1 [Knight, Elysse M.; Kim, Soong Ho; Kottwitz, Jessica C.; Lublin, Alex; Gandy, Sam; Steele, John W.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Knight, Elysse M.; Kim, Soong Ho; Kottwitz, Jessica C.; Lublin, Alex; Ehrlich, Michelle; Gandy, Sam; Steele, John W.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Ehrlich, Michelle] Icahn Sch Med Mt Sinai, Dept Pediat, New York, NY 10029 USA. [Knight, Elysse M.; Kim, Soong Ho; Kottwitz, Jessica C.; Lublin, Alex; Ehrlich, Michelle; Gandy, Sam; Steele, John W.] Icahn Sch Med Mt Sinai, Alzheimers Dis Res Ctr, New York, NY 10029 USA. [Hatami, Asa; Albay, Ricardo; Glabe, Charles G.] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92717 USA. [Hatami, Asa; Albay, Ricardo; Glabe, Charles G.] KAU, King Fahd Med Res Ctr, Jeddah, Saudi Arabia. [Suzuki, Akinobu] Toyama Univ, Grad Sch Med & Pharmaceut Sci, Fac Med, Dept Biochem, Toyama, Toyama, Japan. [Alberini, Cristina M.] NYU, Ctr Neural Sci, New York, NY 10003 USA. [Klein, William L.] Northwestern Univ, Chicago, IL 60611 USA. [Szabo, Paul; Relkin, Norman R.] Weill Cornell Med Coll, Dept Neurol, New York, NY USA. [Szabo, Paul; Relkin, Norman R.] Weill Cornell Med Coll, Brain Mind Res Inst, New York, NY USA. [Glabe, Charles G.] King Abdulaziz Univ, Fac Sci, Dept Biochem, Jeddah, Saudi Arabia. [Glabe, Charles G.] King Abdulaziz Univ, Expt Biochem Unit, King Fahd Med Res Ctr, Jeddah, Saudi Arabia. [Gandy, Sam] James J Peters VA Med Ctr, Bronx, NY USA. [Steele, John W.] Univ Calif San Diego, Sanford Consortium Regenerat Med, La Jolla, CA 92093 USA. RP Gandy, S (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.; Gandy, S (reprint author), Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA.; Gandy, S (reprint author), Icahn Sch Med Mt Sinai, Alzheimers Dis Res Ctr, New York, NY 10029 USA.; Gandy, S (reprint author), James J Peters VA Med Ctr, Bronx, NY USA. EM Samuel.Gandy@mssm.edu RI Faculty of, Sciences, KAU/E-7305-2017 FU NIA NIH HHS [P01 AG000538]; NIGMS NIH HHS [K12 GM068524]; NIMH NIH HHS [R37 MH065635] NR 40 TC 4 Z9 4 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2332-7812 J9 NEUROL-NEUROIMMUNOL JI Neurol.-Neuroimmunol. Neuroinflammation PD JUN PY 2016 VL 3 IS 3 AR e237 DI 10.1212/NXI.0000000000000237 PG 10 WC Neurosciences SC Neurosciences & Neurology GA DX7OO UT WOS:000384577900019 PM 27218118 ER PT J AU Kim, K Yoo, I Woo, JM Lee, SH Fava, M Mischoulon, D Papakostas, GI Kim, EJ Chung, SH Ha, JH Jeon, HJ AF Kim, Kiwon Yoo, Ikki Woo, Jong-Min Lee, Seung-Hwan Fava, Maurizio Mischoulon, David Papakostas, George I. Kim, Eui-Joong Chung, Seock Hoon Ha, Jee Hyun Jeon, Hong Jin TI Influence of anxiety symptoms on improvement of neurocognitive functions in patients with major depressive disorder: A 12-week, multicenter, randomized trial of tianeptine versus escitalopram, the CAMPION study SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 30th Seoul World Congress of the International-College-of-Neuropsychopharmacology (CINP) CY JUL 03-07, 2016 CL Seoul, SOUTH KOREA SP Int Coll Neuropsychopharmacol C1 [Kim, Kiwon; Yoo, Ikki; Jeon, Hong Jin] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, Seoul, South Korea. [Jeon, Hong Jin] Samsung Adv Inst Hlth Sci & Technol SAIHST, Dept Clin Res Design & Evaluat, Seoul, South Korea. [Jeon, Hong Jin] Samsung Adv Inst Hlth Sci & Technol SAIHST, Dept Med Device Management & Res, Seoul, South Korea. [Fava, Maurizio; Mischoulon, David; Papakostas, George I.; Jeon, Hong Jin] Harvard Med Sch, Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA USA. [Woo, Jong-Min] Inje Univ, Sch Med, Seoul Paik Hosp, Dept Psychiat, Seoul, South Korea. [Lee, Seung-Hwan] Inje Univ, Sch Med, Dept Psychiat, Ilsan Paik Hosp, Ilsan, South Korea. [Kim, Eui-Joong] Eulji Univ, Sch Med, Eulji Gen Hosp, Dept Psychiat, Seoul, South Korea. [Chung, Seock Hoon] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Psychiat, Seoul, South Korea. [Ha, Jee Hyun] Konkuk Univ, Dept Psychiat, Sch Med, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2016 VL 19 SU 1 MA PS89 BP 77 EP 78 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA DW8PI UT WOS:000383917600206 ER PT J AU Kim, J Chang, KA Kim, K Fava, M Mischoulon, D Hong, JP Kim, D Heo, JY Jeon, HJ AF Kim, Jiyeon Chang, Kyung-Ah Kim, Kiwon Fava, Maurizio Mischoulon, David Hong, Jin Pyo Kim, Daniel Heo, Jung-Yoon Jeon, Hong Jin TI Differences in hypochondriasis between Korean and American outpatients with major depressive disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 30th Seoul World Congress of the International-College-of-Neuropsychopharmacology (CINP) CY JUL 03-07, 2016 CL Seoul, SOUTH KOREA SP Int Coll Neuropsychopharmacol C1 Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, Seoul, South Korea. Harvard Med Sch, Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA USA. Sungkyunkwan Univ, Dept Hlth Sci & Technol, Dept Med Device Management & Res, Seoul, South Korea. Sungkyunkwan Univ, Dept Clin Res Design & Evaluat, Samsung Adv Inst Hlth Sci & Technol SAIHST, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2016 VL 19 SU 1 MA PS90 BP 78 EP 78 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA DW8PI UT WOS:000383917600207 ER PT J AU Heo, JY Jeon, HJ Fava, M Mischoulon, D Baer, L Clain, A Doorley, J Pisoni, A Papakostas, GI AF Heo, Jung-Yoon Jeon, Hong Jin Fava, Maurizio Mischoulon, David Baer, Lee Clain, Alisabet Doorley, James Pisoni, Angela Papakostas, George I. TI Efficacy of ziprasidone monotherapy in patients with anxious depression: A 12-week, randomized, double-blind, placebo-controlled, sequential-parallel comparison trial SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 30th Seoul World Congress of the International-College-of-Neuropsychopharmacology (CINP) CY JUL 03-07, 2016 CL Seoul, SOUTH KOREA SP Int Coll Neuropsychopharmacol DE Ziprasidone; Major depressive disorder; Anxious depression; Efficacy; Monotherapy C1 [Heo, Jung-Yoon; Jeon, Hong Jin] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, Seoul, South Korea. [Jeon, Hong Jin; Fava, Maurizio; Mischoulon, David; Baer, Lee; Clain, Alisabet; Doorley, James; Pisoni, Angela; Papakostas, George I.] Harvard Med Sch, Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA USA. [Jeon, Hong Jin] Samsung Adv Inst Hlth Sci & Technol SAIHST, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2016 VL 19 SU 1 MA PS153 BP 102 EP 102 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA DW8PI UT WOS:000383917600269 ER PT J AU Sher, L Grunebaum, MF Sullivan, GM Burke, AK Cooper, TB Mann, JJ Oquendo, MA AF Sher, Leo Grunebaum, Michael F. Sullivan, Gregory M. Burke, Ainsley K. Cooper, Thomas B. Mann, J. John Oquendo, Maria A. TI Association of testosterone levels and future suicide attempts in women with bipolar disorder: A prospective study SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 30th Seoul World Congress of the International-College-of-Neuropsychopharmacology (CINP) CY JUL 03-07, 2016 CL Seoul, SOUTH KOREA SP Int Coll Neuropsychopharmacol C1 [Sher, Leo; Grunebaum, Michael F.; Sullivan, Gregory M.; Burke, Ainsley K.; Cooper, Thomas B.; Mann, J. John; Oquendo, Maria A.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Sher, Leo; Grunebaum, Michael F.; Sullivan, Gregory M.; Burke, Ainsley K.; Cooper, Thomas B.; Mann, J. John; Oquendo, Maria A.] Columbia Univ Coll Phys & Surg, 630 W 168th St, New York, NY 10032 USA. [Sher, Leo] James J Peters Vet Adm Med Ctr, New York, NY USA. [Sher, Leo] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2016 VL 19 SU 1 MA PS278 BP 147 EP 148 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA DW8PI UT WOS:000383917600394 ER PT J AU Yoo, HJ Hong, JP Cho, MJ Fava, M Mischoulon, D Heo, JY Kim, K Jeon, HJ AF Yoo, Hye Jin Hong, Jin Pyo Cho, Maeng Je Fava, Maurizio Mischoulon, David Heo, Jung-Yoon Kim, Kiwon Jeon, Hong Jin TI Lifetime suicidal ideation and attempt in community adults with full major depressive disorder versus only sustained depressed mood SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 30th Seoul World Congress of the International-College-of-Neuropsychopharmacology (CINP) CY JUL 03-07, 2016 CL Seoul, SOUTH KOREA SP Int Coll Neuropsychopharmacol DE Depressed mood; Major depressive disorder; Suicidal ideation; Suicide attempt C1 [Yoo, Hye Jin; Hong, Jin Pyo; Heo, Jung-Yoon; Kim, Kiwon] Sungkyunkwan Univ, Samsung Med Ctr, Dept Psychiat, Depress Ctr,Sch Med, Seoul, South Korea. [Cho, Maeng Je; Jeon, Hong Jin] Seoul Natl Univ, Dept Psychiat & Behav Sci, Coll Med, Seoul, South Korea. [Fava, Maurizio; Mischoulon, David; Jeon, Hong Jin] Harvard Med Sch, Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA USA. [Jeon, Hong Jin] Sungkyunkwan Univ, SAIHST, Dept Med Device Management & Res, Dept Hlth Sci & Technol, Seoul, South Korea. [Jeon, Hong Jin] Sungkyunkwan Univ, SAIHST, Dept Clin Res Design & Evaluat, Seoul, South Korea. EM jeonhj@skku.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2016 VL 19 SU 1 MA PS281 BP 148 EP 149 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA DW8PI UT WOS:000383917600397 ER PT J AU Stanifer, JW Muiru, A Jafar, TH Patel, UD AF Stanifer, John W. Muiru, Anthony Jafar, Tazeen H. Patel, Uptal D. TI Chronic kidney disease in low- and middle-income countries SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE epidemiology; multidisciplinary; noncommunicable diseases; urbanization ID RENAL REPLACEMENT THERAPY; CROSS-SECTIONAL SURVEY; RISK-FACTORS; ADULT-POPULATION; HIGH PREVALENCE; AFRICAN POPULATIONS; PERITONEAL-DIALYSIS; SYSTEMATIC ANALYSIS; GLOBAL BURDEN; ARAB-WORLD AB Most of the global burden of chronic kidney disease (CKD) is occurring in low-and middle-income countries (LMICs). As a result of rapid urbanization in LMICs, a growing number of populations are exposed to numerous environmental toxins, high infectious disease burdens and increasing rates of noncommunicable diseases. For CKD, this portends a high prevalence related to numerous etiologies, and it presents unique challenges. A better understanding of the epidemiology of CKD in LMICs is urgently needed, but this must be coupled with strong public advocacy and broad, collaborative public health efforts that address environmental, communicable, and non-communicable risk factors. C1 [Stanifer, John W.; Patel, Uptal D.] Duke Univ, Dept Med, Div Nephrol, Durham, NC 27705 USA. [Stanifer, John W.; Patel, Uptal D.] Duke Univ, Duke Global Hlth Inst, Durham, NC 27710 USA. [Stanifer, John W.; Patel, Uptal D.] Duke Univ, Duke Clin Res Inst, Durham, NC 27705 USA. [Muiru, Anthony] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Jafar, Tazeen H.] Duke NUS Grad Med Sch, Hlth Serv & Syst Res, Singapore, Singapore. RP Stanifer, JW (reprint author), Duke Univ, Dept Med, Div Nephrol, Durham, NC 27705 USA.; Stanifer, JW (reprint author), Duke Univ, Duke Global Hlth Inst, Durham, NC 27710 USA.; Stanifer, JW (reprint author), Duke Univ, Duke Clin Res Inst, Durham, NC 27705 USA. EM john.stanifer@duke.edu FU American Kidney Fund Clinical Scientist in Nephrology Fellowship; National Institute of Diabetes, Digestive and Kidney Diseases of the National Institutes of Health [R01DK93938, R34DK102166, P30DK096493] FX J.W.S. receives support from the American Kidney Fund Clinical Scientist in Nephrology Fellowship and U.D.P. receives support from the National Institute of Diabetes, Digestive and Kidney Diseases of the National Institutes of Health under Award Numbers R01DK93938, R34DK102166 and P30DK096493. NR 80 TC 5 Z9 5 U1 3 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD JUN PY 2016 VL 31 IS 6 BP 868 EP 874 DI 10.1093/ndt/gfv466 PG 7 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA DT1AG UT WOS:000381213500005 PM 27217391 ER PT J AU Clardy, SM Kohler, RH Vinegoni, C Iwamoto, Y Keliher, EJ Weissleder, R AF Clardy, Susan M. Kohler, Rainer H. Vinegoni, Claudio Iwamoto, Yoshiko Keliher, Edmund J. Weissleder, Ralph TI Two-photon imaging of pancreatic beta cells in real time in vivo SO TECHNOLOGY LA English DT Article DE Glucagon-Like Peptide-1; Pancreatic Beta Cells; Multiphoton Imaging; Diabetes Research; Targeted Labelling ID PEPTIDE-1 RECEPTOR; QUANTIFICATION; MICROSCOPY; MASS; TOOL AB Here we present the first generation of two-photon beta cell specific in vivo imaging probes based on GLP1R targeting peptides. Among the three compounds of potential interest, we found quite unexpectedly that a squarine-rotaxane conjugate ( 2PEx-647) had near ideal in vivo imaging characteristics. C1 [Clardy, Susan M.; Kohler, Rainer H.; Vinegoni, Claudio; Iwamoto, Yoshiko; Keliher, Edmund J.; Weissleder, Ralph] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Med Sch, Dept Syst Biol, 200 Longwood Ave,Alpert 536, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA.; Weissleder, R (reprint author), Harvard Med Sch, Dept Syst Biol, 200 Longwood Ave,Alpert 536, Boston, MA 02115 USA. EM rweissleder@mgh.harvard.edu NR 17 TC 0 Z9 0 U1 1 U2 1 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 2339-5478 EI 2345-7740 J9 TECHNOLOGY JI Technology PD JUN PY 2016 VL 4 IS 2 BP 130 EP 134 DI 10.1142/S2339547816200028 PG 5 WC Engineering, Multidisciplinary SC Engineering GA DX5SY UT WOS:000384443400008 ER PT J AU Eberlein, B Santos, AF Mayorga, C Nopp, A Ferrer, M Rouzaire, P Ebo, D Sabato, V Sanz, ML Pecaric-Petkovic, T Patil, SU Hausmann, OV Shreffler, WG Korosec, P Knol, EF Hoffmann, HJ AF Eberlein, Bernadette Santos, Alexandra F. Mayorga, Cristobalina Nopp, Anna Ferrer, Marta Rouzaire, Paul Ebo, Didier Sabato, Vito Sanz, Maria L. Pecaric-Petkovic, Tatjana Patil, Sarita U. Hausmann, Oliver V. Shreffler, Wayne G. Korosec, Peter Knol, Edward F. Hoffmann, Hans Jurgen TI Basophil activation testing in diagnosis and monitoring of allergic disease - an overview SO ALLERGO JOURNAL LA English DT Article DE basophil granulocyte; CD63; BAT; basophil activation test; allergy diagnosis; allergy monitoring; allergen provocation; challenge testing ID VENOM ALLERGY; THRESHOLD-SENSITIVITY; CHRONIC URTICARIA; FLOW-CYTOMETRY; UP-REGULATION; CD-SENS; IMMUNOTHERAPY; EXPRESSION; CD203C; PREDICTS AB The nature of basophil activation as an ex vivo challenge makes it a multifaceted and promising tool for the allergist. Through the development of flow cytometry, discovery of activation markers such as CD63 and markers identifying basophil granulocytes, the basophil activation test ( BAT) has become a pervasive test. BAT measures basophil response to allergen crosslinking IgE on between 150 and 2,000 basophil granulocytes with remarkable analytical sensitivity in < 0.1 ml fresh blood. Dichotomous activation is assessed as the fraction of reacting basophils. In patients with food-, insect venom-, and drug allergy and patients with chronic urticaria BAT can be part of the diagnostic evaluation in addition to history, skin prick testing, and specific IgE determination. BAT may also be helpful in determining the clinically relevant allergen. Basophil sensitivity may be used to monitor patients on allergen immunotherapy, anti-IgE treatment, or in the natural resolution of allergy. The test may use fewer resources and be more reproducible than oral, sting, nasal or bronchial challenge testing. BAT may be useful before challenge testing as it is less stressful for the patient and avoids severe allergic reactions. It may be useful before challenge testing. An important next step is to standardize BAT and make it available in diagnostic laboratories. This article provides an overview of the practical and technical details as well as the utility of BAT in diagnosis and management of allergic diseases. C1 [Eberlein, Bernadette] Tech Univ Munich, Dept Dermatol & Allergy Biederstein, Munich, Germany. [Santos, Alexandra F.] Kings Coll London, Div Asthma Allergy & Lung Biol, Dept Paediat Allergy, London, England. [Santos, Alexandra F.] MRC, London, England. [Santos, Alexandra F.] Asthma UK Ctr Allerg Mech Asthma, London, England. [Santos, Alexandra F.] Coimbra Univ Hosp, Immunoallergol Dept, Coimbra, Portugal. [Mayorga, Cristobalina] UMA, Res Lab, Malaga, Spain. [Mayorga, Cristobalina] UMA, Allergy Serv, Malaga, Spain. [Nopp, Anna] Karolinska Inst, Dept Med Solna, Immunol & Allergy Unit, Stockholm, Sweden. [Nopp, Anna] Karolinska Univ Hosp, Stockholm, Sweden. [Ferrer, Marta; Sanz, Maria L.] Clin Univ Navarra, Dept Allergy & Clin Immunol, Pamplona, Spain. [Rouzaire, Paul] Univ Hosp, Dept Immunol, Clermont Ferrand, France. [Rouzaire, Paul] Univ Auvergne, ERTICa Res Grp, EA4677, Clermont Ferrand, France. [Ebo, Didier; Sabato, Vito] Univ Antwerp, Dept Immunol Allergol Rheumatol, Antwerp, Belgium. [Ebo, Didier; Sabato, Vito] Univ Antwerp Hosp, Antwerp, Belgium. [Pecaric-Petkovic, Tatjana] 0Adverse Drug Reactions Anal & Consulting ADR AC, Bern, Switzerland. [Patil, Sarita U.; Shreffler, Wayne G.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Patil, Sarita U.; Shreffler, Wayne G.] Harvard Med Sch, Boston, MA USA. [Hausmann, Oliver V.] Univ Bern, Inselspital, Dept Rheumatol Immunol & Allergol, Bern, Switzerland. [Hausmann, Oliver V.] Loewenpraxis, Luzern, Switzerland. [Korosec, Peter] Univ Clin Resp & Allerg Dis Golnik, Lab Clin Immunol & Mol Genet, Golnik, Slovenia. [Knol, Edward F.] Univ Med Ctr Utrecht, Dept Immunol, Utrecht, Netherlands. [Knol, Edward F.] Univ Med Ctr Utrecht, Dept Dermatol Allergol, Utrecht, Netherlands. [Hoffmann, Hans Jurgen] Aarhus Univ, Dept Clin Med, Aarhus, Denmark. [Hoffmann, Hans Jurgen] Aarhus Univ Hosp, Dept Resp Dis & Allergy, Aarhus, Denmark. RP Eberlein, B (reprint author), Tech Univ Munich, Dept Dermatol & Allergy Biederstein, Munich, Germany. EM bernadette.eberlein@tum.de RI EBO, Didier/H-4894-2016; OI EBO, Didier/0000-0003-0672-7529; Ferrer, Marta/0000-0001-8495-1302 NR 39 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0941-8849 EI 2195-6405 J9 ALLERGO J JI Allergo J. PD JUN PY 2016 VL 25 IS 4 BP 26 EP 33 DI 10.1007/s40629-016-0113-5 PG 8 WC Allergy SC Allergy GA DW1YE UT WOS:000383438900009 ER PT J AU Puiu, T Kairys, AE Pauer, L Schmidt-Wilcke, T Ichesco, E Hampson, JP Napadow, V Clauw, DJ Harris, RE AF Puiu, Tudor Kairys, Anson E. Pauer, Lynne Schmidt-Wilcke, Tobias Ichesco, Eric Hampson, Johnson P. Napadow, Vitaly Clauw, Daniel J. Harris, Richard E. TI Association of Alterations in Gray Matter Volume With Reduced Evoked-Pain Connectivity Following Short-Term Administration of Pregabalin in Patients With Fibromyalgia SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID INTRINSIC BRAIN CONNECTIVITY; FUNCTIONAL CONNECTIVITY; CLINICAL PAIN; NETWORK; GABAPENTIN; RELEASE; ANATOMY; HUMANS; CORTEX; SCALE AB Objective. Pregabalin (PGB) is an alpha(2)delta calcium-channel subunit ligand that has previously been shown to reduce chronic pain in multiple conditions. Preclinical studies indicate that PGB may down-regulate brain glutamate release while also inhibiting astrocyte induction of glutamatergic synapse formation, and recent clinical findings support the notion that PGB modulates glutamatergic activity and functional brain connectivity in order to produce analgesia. The present study was undertaken to examine concurrent changes in brain gray matter volume (GMV) or evoked-pain connectivity in humans receiving PGB. Methods. Sixteen female fibromyalgia patients participated in a randomized double-blind 2-period crossover study of PGB versus placebo. Before and after each period, patients underwent high-resolution structural and evoked pressure-pain functional brain imaging. GMV was analyzed using voxel-based morphometry, and functional connectivity during evoked pressure-pain was assessed. Results. PGB administration significantly reduced GMV within the posterior insula bilaterally, whereas there were no significant changes in insular GMV following placebo treatment. GMV reductions in the medial frontal gyrus were also observed when comparing PGB versus placebo treatment, and were associated with reduced clinical pain. These reductions in insular GMV were associated with concomitant reductions in connectivity to the default mode network, which was also associated with reduced clinical pain. Conclusion. Short-term PGB treatment altered brain structure and evoked-pain connectivity, and these decreases were associated with reduced clinical pain. We speculate that these fairly rapid changes in GMV may be related to brain neuroplasticity. It is unknown whether these effects are generalizable to other chronic pain states. C1 [Puiu, Tudor; Kairys, Anson E.; Ichesco, Eric; Hampson, Johnson P.; Clauw, Daniel J.; Harris, Richard E.] Univ Michigan, Ann Arbor, MI 48109 USA. [Kairys, Anson E.] Univ Colorado Denver, Denver, CO USA. [Pauer, Lynne] Pfizer Global Res & Dev, Groton, CT USA. [Schmidt-Wilcke, Tobias] Ruhr Univ Bochum, Bochum, Germany. [Napadow, Vitaly] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Napadow, Vitaly] Harvard Med Sch, Boston, MA USA. RP Ichesco, E (reprint author), Univ Michigan, Dept Anesthesiol, Chron Pain & Fatigue Res Ctr, 24 Frank Lloyd Wright Dr, Ann Arbor, MI 48105 USA. EM eichesco@med.umich.edu FU Pfizer; NIH [R21-MH-103468, P01-AT-006663, R01-AT-007550, R01-AR-064367]; Cerephex; Eli Lilly; Merck; Nuvo; Forest; Cypress Biosciences; Theravance Biopharma; Johnson Johnson; Pierre Fabre; Wyeth; UCB; AstraZeneca; Jazz; Abbott; Iroko; Tonix FX Supported by Pfizer. Dr. Napadow's work was supported by NIH grants R21-MH-103468, P01-AT-006663, R01-AT-007550, and R01-AR-064367.; Ms. Pauer owns stock or stock options in Pfizer. Dr. Clauw has received consulting fees from Cerephex, Eli Lilly, Merck, Nuvo, Forest, Cypress Biosciences, Theravance Biopharma, Johnson & Johnson, Pierre Fabre, Wyeth, UCB, AstraZeneca, Jazz, Abbott, and Iroko (less than $10,000 each) and from Pfizer and Tonix (more than $10,000 each) and grant support from Pfizer, Cerephex, Eli Lilly, Merck, Nuvo, Forest, and Cypress Biosciences. Dr. Harris has received consulting fees (less than $10,000) and grant support from Pfizer. NR 50 TC 1 Z9 1 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD JUN PY 2016 VL 68 IS 6 BP 1511 EP 1521 DI 10.1002/art.39600 PG 11 WC Rheumatology SC Rheumatology GA DW2TB UT WOS:000383493600025 PM 26816332 ER PT J AU Ward, MM Deodhar, A Reveille, JD Caplan, L AF Ward, Michael M. Deodhar, Atul Reveille, John D. Caplan, Liron TI Treatment of patients with nonradiographic axial spondyloarthritis who have negative magnetic resonance imaging results and normal C-reactive protein levels at baseline: comment on the article by Ward et al Reply SO ARTHRITIS & RHEUMATOLOGY LA English DT Letter ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; EFFICACY; SACROILIITIS; ADALIMUMAB C1 [Ward, Michael M.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Deodhar, Atul] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Reveille, John D.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Caplan, Liron] Denver Vet Affairs Med Ctr, Aurora, CO USA. [Caplan, Liron] Univ Colorado, Aurora, CO USA. RP Ward, MM (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 AR041153-04] 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD JUN PY 2016 VL 68 IS 6 BP 1563 EP 1564 DI 10.1002/art.39524 PG 3 WC Rheumatology SC Rheumatology GA DW2TB UT WOS:000383493600033 PM 26636978 ER PT J AU Osazuwa-Peters, N Adjei-Boakye, E Loux, TM Varvares, MA Schootman, M AF Osazuwa-Peters, Nosayaba Adjei-Boakye, Eric Loux, Travis M. Varvares, Mark A. Schootman, Mario TI INSUFFICIENT EVIDENCE TO SUPPORT OR REFUTE THE ASSOCIATION BETWEEN HEAD AND NECK CANCER AND MARIJUANA USE SO JOURNAL OF EVIDENCE-BASED DENTAL PRACTICE LA English DT Editorial Material ID RISK; CARCINOMA; UPDATE C1 [Osazuwa-Peters, Nosayaba] St Louis Univ, Ctr Canc, St Louis, MO 63103 USA. [Osazuwa-Peters, Nosayaba] St Louis Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, St Louis, MO 63103 USA. [Osazuwa-Peters, Nosayaba; Schootman, Mario] St Louis Univ, Dept Epidemiol, Coll Publ Hlth & Social Justice, St Louis, MO 63103 USA. [Adjei-Boakye, Eric] SLU COR, St Louis, MO USA. [Loux, Travis M.] St Louis Univ, Coll Publ Hlth & Social Justice, Dept Biostat, St Louis, MO 63103 USA. [Varvares, Mark A.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA USA. RP Osazuwa-Peters, N (reprint author), St Louis Univ, Ctr Canc, St Louis, MO 63103 USA.; Osazuwa-Peters, N (reprint author), St Louis Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, St Louis, MO 63103 USA.; Osazuwa-Peters, N (reprint author), St Louis Univ, Dept Epidemiol, Coll Publ Hlth & Social Justice, St Louis, MO 63103 USA. EM nosazuwa@slu.edu OI Adjei Boakye, Eric/0000-0001-9163-8103; Loux, Travis/0000-0002-9215-0617 NR 9 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-3382 EI 1532-3390 J9 J EVID-BASED DENT PR JI J. Evid.-Based Dent. Pract. PD JUN PY 2016 VL 16 IS 2 BP 127 EP 129 DI 10.1016/j.jebdp.2016.06.004 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DW0VL UT WOS:000383361000013 PM 27449844 ER PT J AU Breyer, BN Fang, SC Seal, KH Ranganathan, G Marx, BP Keane, TM Rosen, RC AF Breyer, Benjamin N. Fang, Shona C. Seal, Karen H. Ranganathan, Gayatri Marx, Brian P. Keane, Terence M. Rosen, Raymond C. TI Sexual Health in Male and Female Iraq and Afghanistan US War Veterans With and Without PTSD: Findings From the VALOR Cohort SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MILITARY PERSONNEL; WOMEN VETERANS; PRIMARY-CARE; DYSFUNCTION; PREVALENCE; PREDICTORS; DEPLOYMENT; HISTORY; ASSAULT AB We sought to determine whether posttraumatic stress disorder (PTSD) was associated with sexual health in returned warzone-deployed veterans from the recent Iraq and Afghanistan conflicts. We studied 1,581 males and females from the Veterans After-Discharge Longitudinal Registry, a gender-balanced U.S. Department of Veterans Affairs registry of health care-seeking veterans with and without PTSD. Approximately one quarter (25.1%) of males (n = 198) and 12.7% of females (n = 101) had a sexual dysfunction diagnosis and/or prescription treatment for sexual dysfunction. Both genders were more likely to have a sexual dysfunction diagnosis and/or prescription treatment if they had PTSD compared with those without PTSD (male: 27.3% vs. 21.1%, p =.054; female: 14.9% vs. 9.4%, p =.022). Among the 1,557 subjects analyzed here, males with PTSD had similar levels of sexual activity compared to those without PTSD (71.2% vs. 75.4%, p =.22), whereas females with PTSD were less likely to be sexually active compared to females without PTSD (58.7% vs. 72.1%, p <.001). Participants with PTSD were also less likely to report sex-life satisfaction (male: 27.6% vs. 46.0%, p <.001; female: 23.0% vs. 45.7%, p<. 001) compared with those without PTSD. Although PTSD was not associated with sexual dysfunction after adjusting for confounding factors, it was significantly negatively associated with sex-life satisfaction in female veterans with a prevalence ratio of .71, 95% confidence interval [.57,.90]. C1 [Breyer, Benjamin N.] Univ Calif San Francisco, Dept Urol, San Francisco, CA USA. [Fang, Shona C.; Ranganathan, Gayatri; Rosen, Raymond C.] New England Res Inst, Div Epidemiol, 9 Galen St, Watertown, MA 02172 USA. [Seal, Karen H.] Univ Calif San Francisco, Vet Adm Med Ctr, Dept Med, San Francisco, CA USA. [Seal, Karen H.] Univ Calif San Francisco, Vet Adm Med Ctr, Dept Psychiat, San Francisco, CA USA. [Marx, Brian P.; Keane, Terence M.] VA Boston Healthcare Syst, Boston, MA USA. [Marx, Brian P.; Keane, Terence M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Marx, Brian P.; Keane, Terence M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. RP Breyer, BN (reprint author), Univ Calif San Francisco, 400 Parnassus Suite A610, San Francisco, CA 94110 USA. EM Benjamin.breyer@ucsf.edu FU U.S. Department of Defense [W81XWH-08-2-0100, W81XWH-08-2-0102]; NIH/NIDDK [K12DK083021] FX Funding for this research was provided by U.S. Department of Defense grants W81XWH-08-2-0100 and W81XWH-08-2-0102 to Terence M. Keane and Raymond C. Rosen. Benjamin N. Breyer was supported by NIH/NIDDK K12DK083021. NR 29 TC 0 Z9 0 U1 5 U2 5 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 JUN PY 2016 VL 29 IS 3 BP 229 EP 236 DI 10.1002/jts.22097 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DW2MZ UT WOS:000383477800005 PM 27128485 ER PT J AU LeBlanc, NJ Dixon, L Robinaugh, DJ Valentine, SE Bosley, HG Gerber, MW Marques, L AF LeBlanc, Nicole J. Dixon, Louise Robinaugh, Donald J. Valentine, Sarah E. Bosley, Hannah G. Gerber, Monica W. Marques, Luana TI PTSD and Romantic Relationship Satisfaction: Cluster- and Symptom-Level Analyses SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; NETWORK ANALYSIS; METAANALYSIS; DEPRESSION; VETERANS; VALIDITY; QUALITY; ADULTS; MODEL; TIME AB Previous studies have demonstrated bidirectional associations between posttraumatric stress disorder (PTSD) and romantic relationship dissatisfaction. Most of these studies were focused at the level of the disorder, examining the association between relationship dissatisfaction and having a diagnosis of PTSD or the total of PTSD symptoms endorsed. This disorder-level approach is problematic for trauma theorists who posit symptom-level mechanisms for these effects. In the present study, we examined the prospective, bidirectional associations between PTSD symptom clusters (e.g., reexperiencing) and relationship satisfaction using the data from 101 previously studied individuals who had had a recent motor vehicle accident. We also conducted exploratory analyses examining the prospective, bidirectional associations between individual PTSD symptoms and relationship satisfaction. Participants had completed the PTSD Checklist-Civilian Version and the Relationship Assessment Scale at 4, 10, and 16 weeks after the MVA. We performed time-lagged mixed-effects regressions to examine the effect of lagged relationship satisfaction on PTSD clusters and symptoms, and vice versa. No cluster effects were significant after controlling for a false discovery rate. Relationship satisfaction predicted prospective decreases in reliving the trauma (d = 0.42), emotional numbness (d = 0.46), and irritability (d = 0.49). These findings were consistent with the position that relationship satisfaction affects PTSD through symptom-level mechanisms. C1 [LeBlanc, Nicole J.] Harvard Univ, Dept Psychol, 1244 William James Hall,33 Kirkland St, Cambridge, MA 02138 USA. [Dixon, Louise] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA USA. [Robinaugh, Donald J.; Valentine, Sarah E.; Gerber, Monica W.; Marques, Luana] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Robinaugh, Donald J.; Valentine, Sarah E.; Marques, Luana] Harvard Med Sch, Dept Psychiat, Boston, MA USA. [Bosley, Hannah G.] Univ Calif Berkeley, Dept Psychol, 3210 Tolman Hall, Berkeley, CA 94720 USA. RP LeBlanc, NJ (reprint author), Harvard Univ, Dept Psychol, 1244 William James Hall,33 Kirkland St, Cambridge, MA 02138 USA. EM nleblanc@fas.harvard.edu OI Bosley, Hannah/0000-0003-4587-314X FU National Institutes of Health [R36 MH015383, K23 MH096029-01A1] FX For the present study we reanalyzed data collected by Dr. Luana Marques for her doctoral dissertation. The dissertation study was funded in part by a grant from the National Institutes of Health (R36 MH015383) awarded to Dr. Marques. Dr. Marques is currently supported by a grant from the National Institutes of Health (K23 MH096029-01A1). We thank Richard J. McNally and Aaron J. Fisher for their helpful suggestions regarding revisions to this manuscript. NR 38 TC 0 Z9 0 U1 8 U2 8 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 JUN PY 2016 VL 29 IS 3 BP 259 EP 267 DI 10.1002/jts.22100 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DW2MZ UT WOS:000383477800009 PM 27163435 ER PT J AU Muralidharan, A Austern, D Hack, S Vogt, D AF Muralidharan, Anjana Austern, David Hack, Samantha Vogt, Dawne TI Deployment Experiences, Social Support, and Mental Health: Comparison of Black, White, and Hispanic US Veterans Deployed to Afghanistan and Iraq SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; DISCRIMINATION; MILITARY; RACE AB Compared to their White counterparts, Black and Hispanic Vietnam-era, male, combat veterans in the United States have experienced discrimination and increased trauma exposure during deployment and exhibited higher rates of postdeployment mental health disorders. The present study examined differences in deployment experiences and postdeployment mental health among male and female Black, Hispanic, and White veterans deployed in support of Operation Enduring Freedom in Afghanistan and Operation Iraqi Freedom in Iraq. Data were drawn from a national survey of veterans (N = 924) who had returned from deployment within the last 2 years. Ethnoracial minority veterans were compared to White veterans of the same gender on deployment experiences and postdeployment mental health. he majority of comparisons did not show significant differences; however, several small group differences did emerge (. 02 N) bi-frontally from 300 to 500 ms, reflecting enhanced familiarity, 2) relative positivity (4R > 1R and 4R > N) in parietal areas from 500 to 800 ms, reflecting enhanced recollection, and 3) late frontal effects (1R > N) from 1000 to 1800 ms in right frontal areas, reflecting post-retrieval monitoring. ET analysis also revealed significant differences in eye movements across conditions. Exploration of cross-modality relationships suggested associations between memory and executive function measures and the three ERP effects. Executive function measures were associated with several indicators of saccadic eye movements and fixations, which were also associated with all three ERP effects. This novel characterization of face-name recognition memory performance using simultaneous EEG and ET reproduced classic ERP and ET effects, supports the construct validity of the multimodal FN paradigm, and holds promise as an integrative tool to probe brain networks supporting memory and executive functioning. C1 [Mitchell, Meghan B.] Tewksbury Hosp, Dept Publ Hlth, 365 East St, Tewksbury, MA 01876 USA. [Shirk, Steven D.; McLaren, Donald G.] ENRM Bedford Vet Affairs Hosp, Res Serv, Bedford, MA USA. [McLaren, Donald G.; Atri, Alireza] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [McLaren, Donald G.; Atri, Alireza] Harvard Med Sch, Boston, MA USA. [Dodd, Jessica S.] Quinnipiac Univ, North Haven, CT USA. [Ezzati, Ali] Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA. [Ally, Brandon A.] Vanderbilt Univ Sch Med, Dept Neurol, Nashville, TN USA. [Atri, Alireza] Ray Dolby Brain Hlth Ctr, San Francisco, CA USA. [Atri, Alireza] Sutter Hlth, Res Inst, Calif Pacific Med Ctr, San Francisco, CA USA. RP Mitchell, MB (reprint author), Tewksbury Hosp, Dept Publ Hlth, 365 East St, Tewksbury, MA 01876 USA. EM meghanbmitchell@gmail.com OI McLaren, Donald/0000-0002-0566-4610; Ezzati, Ali/0000-0003-1307-4589 FU NIA NIH HHS [F32 AG042228, K23 AG027171] NR 44 TC 0 Z9 0 U1 5 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 EI 1931-7565 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD JUN PY 2016 VL 10 IS 2 BP 408 EP 423 DI 10.1007/s11682-015-9420-6 PG 16 WC Neuroimaging SC Neurosciences & Neurology GA DU7JK UT WOS:000382390000008 PM 26116280 ER PT J AU Mellema, JJ Lindenhovius, ALC Jupiter, JB AF Mellema, Jos J. Lindenhovius, Anneluuk L. C. Jupiter, Jesse B. TI The posttraumatic stiff elbow: an update SO CURRENT REVIEWS IN MUSCULOSKELETAL MEDICINE LA English DT Article DE Posttraumatic; Contracture; Elbow; Release; Stiffness ID REVERSED DYNAMIC SLINGS; HETEROTOPIC OSSIFICATION; RISK-FACTORS; FLEXION CONTRACTURE; SURGICAL-TREATMENT; DISTAL HUMERUS; RADIAL HEAD; DISTRACTION ARTHROPLASTY; OPERATIVE RELEASE; LATERAL APPROACH AB Posttraumatic elbow stiffness is a disabling condition that remains challenging to treat despite improvement of our understanding of the pathogenesis of posttraumatic contractures and new treatment regimens. This review provides an update and overview of the etiology of posttraumatic elbow stiffness, its classification, evaluation, nonoperative and operative treatment, and postoperative management. C1 [Mellema, Jos J.; Jupiter, Jesse B.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthoped Surg, Hand & Upper Extrem Serv,Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. [Lindenhovius, Anneluuk L. C.] Univ Amsterdam, Acad Med Ctr, Dept Orthoped Surg, Meibergdreef 9, NL-1100 DD Amsterdam, Netherlands. RP Jupiter, JB (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthoped Surg, Hand & Upper Extrem Serv,Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM jjupiter1@partners.org NR 116 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1935-973X EI 1935-9748 J9 CURR REV MUSCULOSKE JI Curr. Rev. Musculoskelet. Med. PD JUN PY 2016 VL 9 IS 2 BP 190 EP 198 DI 10.1007/s12178-016-9336-9 PG 9 WC Orthopedics SC Orthopedics GA DT1ZP UT WOS:000381280900012 PM 26984466 ER PT J AU Rossy, WH Oh, LS AF Rossy, William H. Oh, Luke S. TI Pitcher's elbow: medial elbow pain in the overhead-throwing athlete SO CURRENT REVIEWS IN MUSCULOSKELETAL MEDICINE LA English DT Article DE Pitcher's elbow; Ulnar collateral ligament; Valgus instability; Medial elbow pain; Posteromedial impingement; Valgus extension overload syndrome ID ULNAR COLLATERAL LIGAMENT; MUSCLE-SPLITTING APPROACH; LEAGUE BASEBALL PITCHERS; BIOMECHANICAL EVALUATION; DOCKING TECHNIQUE; RECONSTRUCTION; NERVE; PLAYERS; FIXATION; INJURY AB Overhead athletes subject their elbows to significant valgus stresses throughout the throwing cycle. A steady rise in the number of medial-sided elbow injuries over the years has lead to increased awareness regarding the pathophysiology of the "pitcher's elbow." As our understanding of the functional anatomy and throwing biomechanics has become more sophisticated, we have seen a concurrent improvement in the outcomes associated with managing these injuries. Despite this improvement, continued anatomical and biomechanical research is still needed to further optimize outcomes and return to sport. C1 [Rossy, William H.; Oh, Luke S.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Sports Med & Shoulder Serv, 175 Cambridge St, Boston, MA 02114 USA. RP Oh, LS (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Sports Med & Shoulder Serv, 175 Cambridge St, Boston, MA 02114 USA. EM loh@mgh.harvard.edu NR 48 TC 0 Z9 0 U1 7 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1935-973X EI 1935-9748 J9 CURR REV MUSCULOSKE JI Curr. Rev. Musculoskelet. Med. PD JUN PY 2016 VL 9 IS 2 BP 207 EP 214 DI 10.1007/s12178-016-9346-7 PG 8 WC Orthopedics SC Orthopedics GA DT1ZP UT WOS:000381280900014 PM 27260266 ER PT J AU Fedorka, CJ Oh, LS AF Fedorka, Catherine J. Oh, Luke S. TI Posterolateral rotatory instability of the elbow SO CURRENT REVIEWS IN MUSCULOSKELETAL MEDICINE LA English DT Article DE Posterolateral rotatory instability; Lateral ulnar collateral ligament; Elbow; Reconstruction; Repair ID ULNAR COLLATERAL LIGAMENT; SURGICAL RECONSTRUCTION; LATERAL EPICONDYLITIS; FUNCTIONAL-ANATOMY; COMPLEX; STABILIZERS; RECURRENT; OUTCOMES AB Posterolateral rotatory instability of the elbow is often caused by a complex injury to the lateral ulnar collateral ligament complex. This often leads to chronic mechanical symptoms of instability and pain. Surgical repair or reconstruction of the ligament is often required to stabilize the radiocapitellar joint. Multiple techniques have been described in the literature for repair or reconstruction of the lateral ligamentous complex with overall good clinical outcomes. C1 [Fedorka, Catherine J.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthopaed Surg, MGH Shoulder Serv, 55 Fruit St,Yawkey 3G, Boston, MA 02114 USA. [Oh, Luke S.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthopaed Surg, MGH Sports Med & Shoulder Serv, 175 Cambridge St,Suite 400, Boston, MA 02114 USA. RP Oh, LS (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthopaed Surg, MGH Sports Med & Shoulder Serv, 175 Cambridge St,Suite 400, Boston, MA 02114 USA. EM loh@mgh.harvard.edu NR 34 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1935-973X EI 1935-9748 J9 CURR REV MUSCULOSKE JI Curr. Rev. Musculoskelet. Med. PD JUN PY 2016 VL 9 IS 2 BP 240 EP 246 DI 10.1007/s12178-016-9345-8 PG 7 WC Orthopedics SC Orthopedics GA DT1ZP UT WOS:000381280900018 PM 27194295 ER PT J AU Fischer, DB Perez, DL Prasad, S Rigolo, L O'Donnell, L Acar, D Meadows, ME Baslet, G Boes, AD Golby, AJ Dworetzky, BA AF Fischer, David B. Perez, David L. Prasad, Sashank Rigolo, Laura O'Donnell, Lauren Acar, Diler Meadows, Mary-Ellen Baslet, Gaston Boes, Aaron D. Golby, Alexandra J. Dworetzky, Barbara A. TI Right inferior longitudinal fasciculus lesions disrupt visual-emotional integration SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE dissociative disorders; derealization; emotions; visual hypoemotionality ID KLUVER-BUCY-SYNDROME; HUMAN CORPUS-CALLOSUM; DEPERSONALIZATION DISORDER; RIGHT-HEMISPHERE; CAPGRAS DELUSION; SEX-DIFFERENCES; TEMPORAL-LOBE; WHITE-MATTER; HYPOEMOTIONALITY; DISCONNECTION AB The mechanism by which the brain integrates visual and emotional information remains incompletely understood, and can be studied through focal lesions that selectively disrupt this process. To date, three reported cases of visual hypoemotionality, a vision-specific form of derealization, have resulted from lesions of the temporo-occipital junction. We present a fourth case of this rare phenomenon, and investigate the role of the inferior longitudinal fasciculus ( ILF) in the underlying pathophysiology. A 50-year-old right-handed male was found to have a right medial temporal lobe tumor following new-onset seizures. Interstitial laser ablation of the lesion was complicated by a right temporo-parieto-occipital intraparenchymal hemorrhage. The patient subsequently experienced emotional estrangement from visual stimuli. A lesion overlap analysis was conducted to assess involvement of the ILF by this patient's lesion and those of the three previously described cases, and diffusion tensor imaging was acquired in our case to further investigate ILF disruption. All four lesions specifically overlapped with the expected trajectory of the right ILF, and diminished structural integrity of the right ILF was observed in our case. These findings implicate the ILF in visual hypoemotionality, suggesting that the ILF is critical for integrating visual information with its emotional content. C1 [Fischer, David B.] Harvard Med Sch, Boston, MA 02115 USA. [Fischer, David B.; Boes, Aaron D.] Harvard Med Sch, Dept Neurol, Berenson Allen Ctr Noninvas Brain Stimulat, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Perez, David L.; Boes, Aaron D.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Perez, David L.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Perez, David L.; Baslet, Gaston] Harvard Med Sch, Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Prasad, Sashank; Acar, Diler; Meadows, Mary-Ellen; Dworetzky, Barbara A.] Harvard Med Sch, Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Rigolo, Laura; O'Donnell, Lauren; Golby, Alexandra J.] Harvard Med Sch, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. RP Perez, DL (reprint author), Massachusetts Gen Hosp, Dept Neurol, 149 13th St, Charlestown, MA 02129 USA. EM dlperez@partners.org FU Howard Hughes Medical Institute; Parkinson's Disease Foundation; National Institute of Neurological Disorders and Stroke [R25NS065743-05S1]; National Institutes of Health [5 R21 NS070572]; National Center for Image-Guided Therapy [P41EB015898] FX This work was supported by the Howard Hughes Medical Institute to D.B.F.; the Parkinson's Disease Foundation to D.B.F.; the National Institute of Neurological Disorders and Stroke [grant number R25NS065743-05S1 to D.L.P.]; the National Institutes of Health [grant number 5 R21 NS070572 to A.J.G.]; and the National Center for Image-Guided Therapy [grant number P41EB015898 to A.J.G.]. NR 37 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 EI 1749-5024 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD JUN PY 2016 VL 11 IS 6 BP 945 EP 951 DI 10.1093/scan/nsw011 PG 7 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA DT1GO UT WOS:000381229900010 PM 26940563 ER PT J AU Vopat, BG Wong, JE Vorys, GC Golijanin, P Provencher, MT AF Vopat, Bryan G. Wong, Jeffrey E. Vorys, George C. Golijanin, Petar Provencher, Matthew T. TI Bicep Tenodesis Techniques With Rotator Cuff Tears: Fork, Rope, and Open SO TECHNIQUES IN SHOULDER AND ELBOW SURGERY LA English DT Article DE biceps tenodesis; technique; fork; rope ID SUPERIOR LABRUM ANTERIOR; LONG HEAD; BUTTON FIXATION; TENDON; SHOULDER; TENDINOPATHY; LESION AB The long head of the bicep (LHB) brachii tendon is a wellknown pain generator in the shoulder. However, it can be difficult to identify the LHB as the cause of the pain as it commonly is combined with other shoulder conditions. Initial treatment of LHB tendon pathologies is usually nonoperative treatment; however, if this fails the surgical options include tenotomy versus tenodesis. Tenotomies can be done quickly and commonly relieve pain associated with the pathology and requires less postoperative restrictions and rehabilitation compared with tenodesis. Despite these advantages, a tenodesis is recommended in patients less than 40 years of age with high physical activity demands, people who have a concern for cosmetics, and patients involved in workers compensation claims. When looking at the different methods of bicep tenodesis, the literature is lacking with regard to which technique is superior. There are multiple different techniques for LHB tenodesis including arthroscopically or an open manner, either above the bicipital groove or through a subpectoral approach. Future studies should be aimed at which position (proximal or distal) and type of fixation is superior when performing a LHB tenodesis. C1 [Vopat, Bryan G.; Wong, Jeffrey E.; Vorys, George C.; Golijanin, Petar; Provencher, Matthew T.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthopaed, Sports Med Serv, 175 Cambridge St,4th Floor, Boston, MA 02114 USA. RP Provencher, MT (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthopaed, Sports Med Serv, 175 Cambridge St,4th Floor, Boston, MA 02114 USA. EM mtprovencher@partners.org NR 23 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1523-9896 EI 1539-591X J9 TECH SHOULDER ELBOW JI TECH. SHOULDER ELBOW SURG. PD JUN PY 2016 VL 17 IS 2 BP 72 EP 76 DI 10.1097/BTE.0000000000000072 PG 5 WC Orthopedics SC Orthopedics GA DV4CB UT WOS:000382871300005 ER PT J AU Zhang, J Wu, CL AF Zhang, Jing Wu, Chin-Lee TI A study of the new five tiered prostate cancer Gleason grading system in a nationwide population cohort in Sweden SO TRANSLATIONAL CANCER RESEARCH LA English DT Editorial Material C1 [Zhang, Jing] Second Mil Med Univ, Changhai Hosp, Dept Pathol, Shanghai 200433, Peoples R China. [Zhang, Jing; Wu, Chin-Lee] Harvard Med Univ, Massachusetts Gen Hosp, Dept Pathol & Urol, Warren Bldg 105,55 Fruit St, Boston, MA 02114 USA. RP Wu, CL (reprint author), Harvard Med Univ, Massachusetts Gen Hosp, Dept Pathol & Urol, Warren Bldg 105,55 Fruit St, Boston, MA 02114 USA. EM CWU2@MGH.HARVARD.EDU NR 4 TC 0 Z9 0 U1 0 U2 0 PU AME PUBL CO PI SHEUNG WAN PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG 00000, PEOPLES R CHINA SN 2218-676X EI 2219-6803 J9 TRANSL CANCER RES JI Transl. Cancer Res. PD JUN PY 2016 VL 5 IS 3 BP 233 EP 233 DI 10.21037/tcr.2016.06.23 PG 1 WC Oncology SC Oncology GA DU5AP UT WOS:000382224600004 ER PT J AU Mooney-Doyle, K Deatrick, JA AF Mooney-Doyle, Kim Deatrick, Janet A. TI Parenting in the face of childhood life-threatening conditions: The ordinary in the context of the extraordinary SO PALLIATIVE & SUPPORTIVE CARE LA English DT Article DE Palliative care; Pediatric; Parenting; Qualitative description; Life-threatening condition ID PALLIATIVE CARE; BEREAVED SIBLINGS; SERIOUS ILLNESS; CHILDREN; CANCER; FAMILIES; PERSPECTIVES; FRAMEWORK; DISTRESS; OUTCOMES AB Objective: Uncovering what it means to be a parent during the extraordinary time of a child's life-threatening condition (LTC) is important for understanding family goals, decision making, and the work of parenting within this context. Method: Qualitative descriptive methods were employed to describe the everyday experience of parenting both children who have an LTC and their healthy siblings. Results: Some 31 parents of 28 children with an LTC who have healthy siblings participated in our study. Four themes emerged from the data that describe a parental desire to maintain emotional connection with all of their children, how parents use cues from their children to know them better and develop parenting strategies, how parents change as a result of caring for a child with an LTC, and how they strive to decrease suffering for all of their children. Significance of results: The findings of our study have implications for clinical practice, family-focused research, and health policy pertaining to families of children with life threatening conditions. C1 [Mooney-Doyle, Kim] Univ Penn, Sch Nursing, Ctr Global Womens Hlth, Philadelphia, PA 19104 USA. [Mooney-Doyle, Kim; Deatrick, Janet A.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. RP Mooney-Doyle, K (reprint author), Univ Penn, Sch Nursing, 418 Curie Blvd, Philadelphia, PA 19104 USA. EM kemooney@nursing.upenn.edu FU National Institutes of Health/National Institute for Nursing Research Ruth L. Kirschstein National Research Service Award [5F31-NR011533-03]; [T32NR007100] FX The authors acknowledge receipt of the following financial support for the research, authorship, and/or publication of this article. The National Institutes of Health/National Institute for Nursing Research Ruth L. Kirschstein National Research Service Award (5F31-NR011533-03 PI: Mooney-Doyle) supported our study. Dr. Mooney-Doyle is also currently supported by an institutional training grant (T32NR007100 PI: Sommers). NR 40 TC 1 Z9 1 U1 4 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1478-9515 EI 1478-9523 J9 PALLIAT SUPPORT CARE JI Palliat. Support Care PD JUN PY 2016 VL 14 IS 3 BP 187 EP 198 DI 10.1017/S1478951515000905 PG 12 WC Health Policy & Services SC Health Care Sciences & Services GA DT2DF UT WOS:000381290300003 PM 26462446 ER PT J AU Aligeti, S Baig, MR Barrera, FF AF Aligeti, Sabitha Baig, Muhammad R. Barrera, Fernando F. TI Terminal delirium misdiagnosed as major psychiatric disorder: Palliative care in a psychiatric inpatient unit SO PALLIATIVE & SUPPORTIVE CARE LA English DT Article DE Delirium; Terminal delirium; Depression; Dementia; End-of-life care ID DEATH; LIFE AB Background: Delirium is a neuropsychiatric condition characterized by acute change in cognition and disturbance of consciousness. A similar state during the final days of life is termed "terminal delirium." Method: We present three cases with end-stage chronic medical problems without any significant psychiatric history who were admitted to an inpatient psychiatric unit or a locked dementia unit for management of "depression," "dementia," or "psychosis." Conclusions: Early diagnosis of terminal delirium helps prevent patients, family members, and staff from undergoing severe emotional distress and facilitates appropriate end-of-life care. C1 [Baig, Muhammad R.] Audie L Murphy VA Hosp, South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Aligeti, Sabitha] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Barrera, Fernando F.] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, San Antonio, TX 78229 USA. RP Baig, MR (reprint author), Audie L Murphy VA Hosp, South Texas Vet Hlth Care Syst, San Antonio, TX USA.; Baig, MR (reprint author), 7400 Merton Minter, San Antonio, TX 78229 USA. EM raisbaig@hotmail.com NR 15 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 1478-9515 EI 1478-9523 J9 PALLIAT SUPPORT CARE JI Palliat. Support Care PD JUN PY 2016 VL 14 IS 3 BP 307 EP 310 DI 10.1017/S147895151500098X PG 4 WC Health Policy & Services SC Health Care Sciences & Services GA DT2DF UT WOS:000381290300016 PM 26490485 ER PT J AU Walsh, CM Ruoff, L Varbel, J Walker, K Grinberg, LT Boxer, AL Kramer, JH Miller, BL Neylan, TC AF Walsh, Christine M. Ruoff, Leslie Varbel, Jonathan Walker, Kathleen Grinberg, Lea T. Boxer, Adam L. Kramer, Joel H. Miller, Bruce L. Neylan, Thomas C. TI Rest-activity rhythm disruption in progressive supranuclear palsy SO SLEEP MEDICINE LA English DT Article DE Progressive supranuclear palsy; Actigraphy; Sleep; Circadian rhythms ID SLEEP BEHAVIOR DISORDER; RICHARDSON-OLSZEWSKI SYNDROME; PARKINSONS-DISEASE; REM-SLEEP; CIRCADIAN-RHYTHMS; DEMENTIA; SCALE; DEGENERATION; ASSOCIATION; DIAGNOSIS AB Objective/Background: The brainstem is among the first regions affected in progressive supranuclear palsy (PSP) and is part of the sleep/circadian regulation network. In two small studies, blood pressure and core body temperature circadian patterns were disrupted in PSP; however, it is unclear if circadian activity rhythms are also affected. Our objective was to perform circadian analyses of the rest-activity rhythms in PSP and determine the association with increasing disease severity. Patients/Methods: Individuals with a clinical PSP diagnosis (n = 17; nine men) and healthy older adults (n = 17; nine men) were selected for this study. Participants wore actigraphy wristbands and completed sleep diaries for up to 14 consecutive days. Data were analyzed to assess circadian activity strength (amplitude, mesor, f-ratio), phase (acrophase), and circadian stability (intradaily variability, interdaily stability, relative amplitude). Analyses controlled for sleep fragmentation, cognition, and self-reported depression. The association between disease severity using the PSP rating scale and circadian activity rhythm disruption was assessed. Results: Individuals with PSP had significantly lower circadian activity mesor (p <= 0.001), amplitude (<= = 0.001), robustness (f-ratio, p < 0.01), relative amplitude (p <= 0.001), and interdaily stability (p = 0.01), with increased intradaily variability (p < 0.05). CAR remained weaker in PSP after controlling for sleep fragmentation, and again when also controlling for cognitive impairment and depression. Weaker circadian activity (mesor, amplitude, f-ratio, and relative amplitude) was associated with increased disease severity. Conclusions: Circadian activity rhythms are disrupted in individuals with PSP as compared to controls, and worsen with disease severity. This is the first study of its kind to describe circadian activity rhythms in PSP. (C) 2016 Elsevier B.V. All rights reserved. C1 [Walsh, Christine M.; Walker, Kathleen; Grinberg, Lea T.; Boxer, Adam L.; Kramer, Joel H.; Miller, Bruce L.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, 675 Nelson Rising Lane,Suite 190, San Francisco, CA 94158 USA. [Ruoff, Leslie; Varbel, Jonathan; Neylan, Thomas C.] San Francisco VA Med Ctr, Dept Mental Hlth, Stress & Hlth Res Program, 4150 Clement St 116P Bldg 8, San Francisco, CA 94121 USA. [Kramer, Joel H.; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, 401 Parnassus Ave, San Francisco, CA 94143 USA. RP Walsh, CM (reprint author), Memory & Aging Ctr, UCSF MC 1207,675 Nelson Rising Lane,Suite 190, San Francisco, CA 94158 USA. EM christine.walsh@ucsf.edu FU Rainwater Foundation; Hillblom Foundation Network Grant; National Institute on Aging (NIA) [P01 AG019724, RO1 AG038791, U54NS092089, R01 AG032289] FX The authors would like to thank the research coordinators who referred and helped to schedule participants to this study. In particular, we thank Nihar Patel, Jessica Zakrzewski, Nik Block, Aly Caplan, Robert Chen, Ali Dallich, Erwin Kong, Danny Luong, Natanya Russek, Lisa Voltarelli, and Matthew Wynn. This study was financially supported by the Rainwater Foundation (Neylan), Hillblom Foundation Network Grant (Kramer & Miller), National Institute on Aging (NIA) under the following grant numbers: P01 AG019724 (Miller), RO1 AG038791 & U54NS092089 (Boxer), and R01 AG032289 (Kramer). NR 28 TC 1 Z9 1 U1 3 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 EI 1878-5506 J9 SLEEP MED JI Sleep Med. PD JUN PY 2016 VL 22 BP 50 EP 56 DI 10.1016/j.sleep.2016.05.002 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA DU6EI UT WOS:000382306400009 PM 27544836 ER PT J AU Winkelman, JW AF Winkelman, John W. TI Response to Letter to the Editor: "Ferritin deficiency may deteriorate the symptoms of Restless Legs Syndrome" SO SLEEP MEDICINE LA English DT Letter C1 [Winkelman, John W.] Massachusetts Gen Hosp, Dept Psychiat & Neurol, 1 Bowdoin Sq, Boston, MA 02114 USA. RP Winkelman, JW (reprint author), Massachusetts Gen Hosp, Dept Psychiat & Neurol, 1 Bowdoin Sq, Boston, MA 02114 USA. EM JWWINKELMAN@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 EI 1878-5506 J9 SLEEP MED JI Sleep Med. PD JUN PY 2016 VL 22 BP 105 EP 105 DI 10.1016/j.sleep.2015.09.012 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA DU6EI UT WOS:000382306400022 PM 26586594 ER PT J AU Ghoshal, S Fuchs, BC Tanabe, KK AF Ghoshal, Sarani Fuchs, Bryan C. Tanabe, Kenneth K. TI STAT3 is a key transcriptional regulator of cancer stem cell marker CD133 in HCC SO HEPATOBILIARY SURGERY AND NUTRITION LA English DT Editorial Material DE CD133; hepatocellular carcinoma (HCC); signal transducer and activator of transcription factor 3 (STAT3); interleukin-6 (IL-6) ID HEPATOCELLULAR-CARCINOMA; PATHWAY; SIGNAL AB Cancer stem cell (CSC) marker CD133 was found to be upregulated in many cancers including hepatocellular carcinoma (HCC). However, the molecular mechanism of CD133 regulation in the liver tumor microenvironment has remained elusive. In this study Won and colleagues report that interleukin-6 (IL-6) mediated signal transducer and activator of transcription factor 3 (STAT3) signaling and hypoxia enhance the expression of CD133 and promote the progression of HCC. C1 [Ghoshal, Sarani; Fuchs, Bryan C.; Tanabe, Kenneth K.] Harvard Med Sch, Div Surg Oncol, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. RP Tanabe, KK (reprint author), Harvard Med Sch, Div Surg Oncol, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. EM ktanabe@partners.org NR 8 TC 2 Z9 3 U1 1 U2 2 PU AME PUBL CO PI SHEUNG WAN PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG 00000, PEOPLES R CHINA SN 2304-3881 EI 2304-389X J9 HEPATOL SURG NUTR JI HEPATOL. SURG. NUTR. PD JUN PY 2016 VL 5 IS 3 BP 201 EP 203 DI 10.21037/hbsn.2016.03.02 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DT8LI UT WOS:000381741400003 PM 27275460 ER PT J AU Kennedy, S Caldwell, M Bydlon, T Mulvey, C Mueller, J Wilke, L Barry, W Ramanujam, N Geradts, J AF Kennedy, Stephanie Caldwell, Matthew Bydlon, Torre Mulvey, Christine Mueller, Jenna Wilke, Lee Barry, William Ramanujam, Nimmi Geradts, Joseph TI Correlation of breast tissue histology and optical signatures to improve margin assessment techniques SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE breast; margin; scattering; demographics; spectroscopy; histology ID MONTE-CARLO; ADIPOCYTE SIZE; TUMOR MARGINS; INVERSE MODEL; CANCER; SCATTERING; DIAGNOSIS; CELLS; SPECTROSCOPY; VARIABILITY AB Optical spectroscopy is sensitive to morphological composition and has potential applications in intraoperative margin assessment. Here, we evaluate ex vivo breast tissue and corresponding quantified hematoxylin & eosin images to correlate optical scattering signatures to tissue composition stratified by patient characteristics. Adipose sites (213) were characterized by their cell area and density. All other benign and malignant sites (181) were quantified using a grid method to determine composition. The relationships between mean reduced scattering coefficient (), and % adipose, % collagen, % glands, adipocyte cell area, and adipocyte density were investigated. These relationships were further stratified by age, menopausal status, body mass index (BMI), and breast density. We identified a positive correlation between and % collagen and a negative correlation between and age and BMI. Increased collagen corresponded to increased variability. In postmenopausal women, was similar regardless of fibroglandular content. Contributions from collagen and glands to were independent and equivalent in benign sites; glands showed a stronger positive correlation than collagen to in malignant sites. Our data suggest that scattering could differentiate highly scattering malignant from benign tissues in postmenopausal women. The relationship between scattering and tissue composition will support improved scattering models and technologies to enhance intraoperative optical margin assessment. (C) 2016 Society of Photo-Optical Instrumentation Engineers (SPIE) C1 [Kennedy, Stephanie; Caldwell, Matthew; Bydlon, Torre; Mulvey, Christine; Mueller, Jenna; Ramanujam, Nimmi] Duke Univ, TOpS Lab, Dept Biomed Engn, 136 Hudson Hall, Durham, NC 27708 USA. [Wilke, Lee] Univ Wisconsin, Breast Ctr, Dept Surg, 600 Highland Ave, Madison, WI 53792 USA. [Barry, William] Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave,CLS11007, Boston, MA 02215 USA. [Geradts, Joseph] Duke Univ, Med Ctr, Dept Pathol, DUMC3712,200 Trent Dr, Durham, NC 27710 USA. [Geradts, Joseph] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. RP Geradts, J (reprint author), Duke Univ, Med Ctr, Dept Pathol, DUMC3712,200 Trent Dr, Durham, NC 27710 USA.; Geradts, J (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM jgeradts@partners.org FU Department of Defense [W81XWH-05-1-036]; National Institute of Health [1R41CA128160-01]; Duke University's CTSA grant from NCRR/NIH [1 UL1 RR024128-01] FX We would like to thank the Department of Pathology at Duke for providing us access to the H&E slides corresponding to all of the data we have collected. Also, we would like to thank the Duke Comprehensive Cancer Center and the Duke Translational Research Institute for their generous support. The DUMC surgical pathology staff performed the processing of the partial mastectomy specimens. This work was supported by the Department of Defense award W81XWH-05-1-036, National Institute of Health award 1R41CA128160-01, and was supported in part by Duke University's CTSA grant 1 UL1 RR024128-01 from NCRR/NIH. NR 31 TC 0 Z9 0 U1 0 U2 0 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD JUN PY 2016 VL 21 IS 6 AR 066014 DI 10.1117/1.JBO.21.6.066014 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA DU0TL UT WOS:000381917300038 PM 27327487 ER PT J AU Padua, D Vu, JP Germano, PM Pisegna, JR AF Padua, David Vu, John P. Germano, Patrizia M. Pisegna, Joseph R. TI The Role of Neuropeptides in Mouse Models of Colitis SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Pituitary adenylate cyclase-activating polypeptide (PACAP); Vasoactive intestinal polypeptide (VIP); Gastrin; Gastric acid secretion; Gastrointestinal hormones ID VASOACTIVE-INTESTINAL-PEPTIDE; DEXTRAN SULFATE SODIUM; INFLAMMATORY-BOWEL-DISEASE; CYCLASE-ACTIVATING POLYPEPTIDE; ACID-INDUCED COLITIS; EXPERIMENTAL ULCERATIVE COLITIS; INHIBITS CYTOKINE PRODUCTION; EXPERIMENTAL MURINE COLITIS; CD4(+) T-CELLS; CROHNS-DISEASE AB Inflammatory bowel disease (IBD) constitutes an important clinically significant condition that results in morbidity and mortality. IBD can be generally classified into either ulcerative colitis (UC) or Crohn's disease (CD) that differs in the clinical and histopathology. The role of neuropeptides in the pathogenesis of these conditions is becoming increasingly recognized for their importance in modulating the inflammatory state. Animal models provide the greatest insight to better understand the pathophysiology of both disorders which will hopefully allow for improved treatment strategies. This review will provide a better understanding of the role of murine models for studying colitis. C1 [Padua, David; Vu, John P.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Vu, John P.; Germano, Patrizia M.] VA Greater Los Angeles Healthcare Syst, Dept Vet Affairs, Div Pulm, Los Angeles, CA 90073 USA. [Vu, John P.; Germano, Patrizia M.] VA Greater Los Angeles Healthcare Syst, Dept Vet Affairs, Div Crit Care, Los Angeles, CA 90073 USA. [Pisegna, Joseph R.] VA Greater Los Angeles Healthcare Syst, Dept Med, Div Gastroenterol Hepatol & Parenteral Nutr, Los Angeles, CA USA. [Pisegna, Joseph R.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Pisegna, JR (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, Div Gastroenterol Hepatol & Parenteral Nutr, Los Angeles, CA USA.; Pisegna, JR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. EM jpisegna@ucla.edu FU Department of Veterans Affairs RRD [F0873-R]; NIH [DK-41301]; Human Studies CORE through CURE; Digestive Diseases Research Center by NIH [P30DK41301]; NIH NIDDK FX This work received grant support from the Department of Veterans Affairs RR&D Merit Review (JRP), Department of Veterans Affairs RR&D Merit Review F0873-R (PG), NIH DK-41301, Human Studies CORE through CURE, Digestive Diseases Research Center supported by NIH grant P30DK41301, and NIH NIDDK T32 (DP). NR 74 TC 3 Z9 4 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 EI 1559-1166 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD JUN PY 2016 VL 59 IS 2 BP 203 EP 210 DI 10.1007/s12031-015-0688-1 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DS3ZG UT WOS:000380720600004 PM 26646243 ER PT J AU Singh, JA Ramachandran, R AF Singh, Jasvinder A. Ramachandran, Rekha TI Persisting Racial Disparities in Total Shoulder Arthroplasty Utilization and Outcomes SO JOURNAL OF RACIAL AND ETHNIC HEALTH DISPARITIES LA English DT Article DE Race; Total shoulder arthroplasty; TSA; Utilization; Outcomes; Mortality; Hospital stay; Discharge; Time-trends ID PATIENT-PHYSICIAN COMMUNICATION; ELECTIVE JOINT REPLACEMENT; QUALITY-OF-LIFE; KNEE REPLACEMENT; ETHNIC DISPARITIES; UNEQUAL TREATMENT; HIP-REPLACEMENT; UNITED-STATES; HEALTH-CARE; RACE AB Objective The purpose was to study whether racial disparities in total shoulder arthroplasty (TSA) utilization and outcomes have declined over time. Methods We used the US Nationwide Inpatient Sample from 1998 to 2011. We used chi-squared test to compare characteristics, Cochran-Armitage test to compare utilization rates, and Cochran-Armitage test and logistic regression to compare time-trends in outcomes by race. Results From 1998 to 2011, 176,141 Whites and 7694 Blacks underwent TSA. Compared to Whites, Blacks who underwent TSA were younger (69.1 vs. 64.2 years; p < 0.0001), more likely to be female (54.9 vs. 71.0 %; p < 0.0001), and have rheumatoid arthritis or avascular necrosis as the underlying diagnosis (1.7 vs. 3.0% and 1.7 vs. 6.1 %; p < 0.0001 for both) and a Deyo-Charlson index of 2 or higher (8.5 vs. 16.7 %; p < 0.0001). Compared to Whites, Blacks had much lower TSA utilization rate/100,000 in 1998 (2.97 vs. 0.83; p < 0.0001) and in 2011 (12.27 vs. 3.33; p < 0.0001); racial disparities increased from 1998 to 2011 (p < 0.0001). A higher proportion of Blacks than Whites had a hospital stay greater than median in 1998-2000, 62 vs. 51.4 % (p = 0.02), and in 2009-2011, 34.4 vs. 27.3 % (p < 0.0001); disparities did not change over time (p = 0.31). These disparities in utilization were borderline significant in adjusted analyses. There were no racial differences in proportion discharged to inpatient medical facility in 1998-2000, 15.2 vs. 15.0 % (p = 0.95), and in 2009-2011, 12.3 vs. 11.1%(p = 0.37), respectively. Conclusions We found increasing racial disparities in TSA utilization. Some disparities in outcomes exist as well. Patients, surgeons, and policy-makes should be aware of these findings and take action to reduce racial disparities. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.; Ramachandran, Rekha] Univ Alabama Birmingham, Sch Med, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Ramachandran, Rekha] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Dept Orthoped Surg, Coll Med, Rochester, MN USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Birmingham, AL USA.; Singh, JA (reprint author), Univ Alabama Birmingham, Sch Med, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA.; Singh, JA (reprint author), Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA.; Singh, JA (reprint author), Mayo Clin, Dept Orthoped Surg, Coll Med, Rochester, MN USA. EM jasvinder.md@gmail.com NR 44 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 2197-3792 EI 2196-8837 J9 J RACIAL ETHN HEALTH JI J. Racial Ethn. Health Disparities PD JUN PY 2016 VL 3 IS 2 BP 259 EP 266 DI 10.1007/s40615-015-0138-3 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DT5FY UT WOS:000381508200010 PM 27271067 ER PT J AU Graham, SH AF Graham, Steven H. TI Modification of ubiquitin C-terminal hydrolase L1 by reactive lipid species: role in neural regeneration and diseases of aging SO NEURAL REGENERATION RESEARCH LA English DT Article ID UCH-L1; AGGREGATION; NEURONS C1 [Graham, Steven H.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. RP Graham, SH (reprint author), VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. EM Steven.Graham@va.gov FU NIA NIH HHS [P30 AG024827]; NINDS NIH HHS [R01 NS037459]; RRD VA [I01 RX000310] NR 10 TC 0 Z9 0 U1 2 U2 2 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 1673-5374 EI 1876-7958 J9 NEURAL REGEN RES JI Neural Regen. Res. PD JUN PY 2016 VL 11 IS 6 BP 908 EP 909 DI 10.4103/1673-5374.184482 PG 2 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA DS9QU UT WOS:000381119200016 PM 27482212 ER PT J AU Holers, VM Tomlinson, S Kulik, L Atkinson, C Rohrer, B Banda, N Thurman, JM AF Holers, V. Michael Tomlinson, Stephen Kulik, Liudmila Atkinson, Carl Rohrer, Barbel Banda, Nirmal Thurman, Joshua M. TI New therapeutic and diagnostic opportunities for injured tissue-specific targeting of complement inhibitors and imaging modalities SO SEMINARS IN IMMUNOLOGY LA English DT Review DE Therapeutics; Targeting; Natural antibodies; Cell injury; Neoepitopes; Imaging ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; ISCHEMIA-REPERFUSION INJURY; ISCHEMIA/REPERFUSION INJURY; INTESTINAL ISCHEMIA; BINDING-PROTEINS; IN-VIVO; PATHWAY; MEMBRANE; RECEPTOR; INNATE AB Despite substantial opportunity and commercial interest in developing drugs that modulate the complement system in a broad range of non-orphan indications, several obstacles remain to be overcome. Among these issues is the biophysical nature of complement proteins, whose circulating levels are typically very high and whose turnover rates are relatively rapid, especially in the setting of chronic inflammatory conditions. This situation necessitates the use of very high levels of therapeutic compounds in order to achieve both multi-pathway and multiple effector mechanism inhibition. In addition, one must avoid infectious complications or the systemic impairment of the other important physiological functions of complement. Herein we focus on the development of a novel therapeutic strategy based on injured tissue-specific targeting of complement inhibitors using the antigen-combining domains of a small subset of natural IgM antibodies, which as endogenous antibodies specifically recognize sites of local damage across a broad range of tissues and locally activate complement C3, resulting in C3 fragment covalent fixation. Because the use of such recombinant tissue-targeting inhibitors precludes the utility of measuring systemic levels of complement biomarkers or function, since a goal of this targeting strategy is to leave those processes intact and unimpeded, we also briefly describe a new method designed to quantitatively measure using imaging modalities the inhibition of generation of fixed C3 fragments at sites of inflammation/injury. In addition to the ability to determine whether complement activation is locally constrained with the use of inhibitors, there is also a broader application of this imaging approach to inflammatory and autoimmune diseases characterized by local complement activation. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Holers, V. Michael; Kulik, Liudmila; Banda, Nirmal] Univ Colorado, Sch Med, Dept Med & Immunol, Aurora, CO USA. [Tomlinson, Stephen; Rohrer, Barbel] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. [Tomlinson, Stephen; Atkinson, Carl] Med Univ South Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Atkinson, Carl] Med Univ South Carolina, Dept Surg, Transplant Immunobiol Lab, Charleston, SC 29425 USA. [Rohrer, Barbel] Med Univ South Carolina, Dept Ophthalmol, 171 Ashley Ave, Charleston, SC 29425 USA. [Thurman, Joshua M.] Univ Colorado, Sch Med, Dept Med, Aurora, CO USA. RP Holers, VM (reprint author), Univ Colorado, Sch Med, Div Rheumatol, B115,1775 Aurora Court, Aurora, CO 80045 USA. EM Michael.Holers@ucdenver.edu FU National Institutes of Health (NIH) grants [R01 AR051749, R01 DK076690, R01 EY019320, R01 HL091944, P20 GM109040]; KIDNEEDS Foundation; Lupus Research Institute; Department of Veterans Affairs Merit Awards [1I01RX001141, 1BX001218, I01 RX000444]; Research to Prevent Blindness FX This work discussed herein was supported by a National Institutes of Health (NIH) grants R01 AR051749 (VMH), R01 DK076690 (JMT), R01 EY019320 (BR), R01 HL091944 (CA), and P20 GM109040, in addition to a grant from the KIDNEEDS Foundation (JMT), a grant from the Lupus Research Institute (JMT), the Department of Veterans Affairs Merit Awards 1I01RX001141 (ST), 1BX001218 (ST) and I01 RX000444 (BR), and an unrestricted grant to MUSC from Research to Prevent Blindness (BR). NR 63 TC 1 Z9 1 U1 1 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD JUN PY 2016 VL 28 IS 3 BP 260 EP 267 DI 10.1016/j.smim.2016.05.007 PG 8 WC Immunology SC Immunology GA DT9TQ UT WOS:000381845600006 PM 27282113 ER PT J AU Kulkarni, T O'Reilly, P Antony, VB Gaggar, A Thannickal, VJ AF Kulkarni, Tejaswini O'Reilly, Philip Antony, Veena B. Gaggar, Amit Thannickal, Victor J. TI Matrix Remodeling in Pulmonary Fibrosis and Emphysema SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE extracellular matrix; myofibroblasts; transforming growth factor-beta; pulmonary fibrosis; emphysema ID GROWTH-FACTOR-BETA; HUMAN LUNG FIBROBLASTS; ACTIVATES LATENT TGF-BETA-1; TROPOELASTIN MESSENGER-RNA; ALVEOLAR EPITHELIAL-CELLS; SMOKE-INDUCED EMPHYSEMA; POSITIVE FEEDBACK LOOP; EXTRACELLULAR-MATRIX; TGF-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1 AB Pulmonary fibrosis and emphysema are chronic lung diseases characterized by a progressive decline in lung function, resulting in significant morbidity and mortality. A hallmark of these diseases is recurrent or persistent alveolar epithelial injury, typically caused by common environmental exposures such as cigarette smoke. We propose that critical determinants of the outcome of the injury-repair processes that result in fibrosis versus emphysema are mesenchymal cell fate and associated extracellular matrix dynamics. In this review, we explore the concept that regulation of mesenchymal cells under the influence of soluble factors, in particular transforming growth factor-beta 1, and the extracellular matrix determine the divergent tissue remodeling responses seen in pulmonary fibrosis and emphysema. C1 [Kulkarni, Tejaswini; O'Reilly, Philip; Antony, Veena B.; Gaggar, Amit; Thannickal, Victor J.] Univ Alabama Birmingham, Dept Med, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. [Kulkarni, Tejaswini; O'Reilly, Philip; Antony, Veena B.; Gaggar, Amit; Thannickal, Victor J.] Program Protease & Matrix Biol Ctr, Birmingham, AL USA. [Gaggar, Amit; Thannickal, Victor J.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Thannickal, VJ (reprint author), 1900 Univ Blvd,422 THT, Birmingham, AL 35294 USA. EM vjthan@uab.edu FU National Institutes of Health (NIH) [P01 HL114470, R01 AG046210]; NIH [HL102371]; Veteren's Administration grant [I01BX001756] FX This work was supported by National Institutes of Health (NIH) grants P01 HL114470 and R01 AG046210 (V.J.T.), and NIH grant HL102371 and Veteren's Administration grant I01BX001756 (A.G.). NR 116 TC 4 Z9 4 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1044-1549 EI 1535-4989 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JUN 1 PY 2016 VL 54 IS 6 BP 751 EP 760 DI 10.1165/rcmb.2015-0166PS PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA DT7XQ UT WOS:000381702000001 PM 26741177 ER PT J AU Ahluwalia, N Grasberger, PE Mugo, BM Feghali-Bostwick, C Pardo, A Selman, M Lagares, D Tager, AM AF Ahluwalia, Neil Grasberger, Paula E. Mugo, Brian M. Feghali-Bostwick, Carol Pardo, Annie Selman, Moises Lagares, David Tager, Andrew M. TI Fibrogenic Lung Injury Induces Non-Cell-Autonomous Fibroblast Invasion SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE idiopathic pulmonary fibrosis; pathogenesis; fibroblast; invasion; migration ID IDIOPATHIC PULMONARY-FIBROSIS; PROTEIN-COUPLED RECEPTORS; MEDIATED MIGRATION; VASCULAR LEAK; CANCER CELLS; ACID; MYOFIBROBLAST; PROLIFERATION; HYALURONAN; INHIBITION AB Pathologic accumulation of fibroblasts in pulmonary fibrosis appears to depend on their invasion through basement membranes and extracellular matrices. Fibroblasts from the fibrotic lungs of patients with idiopathic pulmonary fibrosis (IPF) have been demonstrated to acquire a phenotype characterized by increased cell-autonomous invasion. Here, we investigated whether fibroblast invasion is further stimulated by soluble mediators induced by lung injury. We found that bronchoalveolar lavage fluids from bleomycin-challenged mice or patients with IPF contain mediators that dramatically increase the matrix invasion of primary lung fibroblasts. Further characterization of this non-cell-autonomous fibroblast invasion suggested that the mediators driving this process are produced locally after lung injury and are preferentially produced by fibrogenic (e.g., bleomycin-induced) rather than nonfibrogenic (e.g., LPS-induced) lung injury. Comparison of invasion and migration induced by a series of fibroblast-active mediators indicated that these two forms of fibroblast movement are directed by distinct sets of stimuli. Finally, knockdown of multiple different membrane receptors, including platelet-derived growth factor receptor-beta, lysophosphatidic acid 1, epidermal growth factor receptor, and fibroblast growth factor receptor 2, mitigated the non-cell-autonomous fibroblast invasion induced by bronchoalveolar lavage from bleomycin-injured mice, suggesting that multiple different mediators drive fibroblast invasion in pulmonary fibrosis. The magnitude of this mediator-driven fibroblast invasion suggests that its inhibition could be a novel therapeutic strategy for pulmonary fibrosis. Further elaboration of the molecular mechanisms that drive non-cell-autonomous fibroblast invasion consequently may provide a rich set of novel drug targets for the treatment of IPF and other fibrotic lung diseases. C1 [Ahluwalia, Neil; Grasberger, Paula E.; Mugo, Brian M.; Lagares, David; Tager, Andrew M.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Ahluwalia, Neil; Grasberger, Paula E.; Mugo, Brian M.; Lagares, David; Tager, Andrew M.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Ahluwalia, Neil; Grasberger, Paula E.; Mugo, Brian M.; Lagares, David; Tager, Andrew M.] Harvard Med Sch, Boston, MA 02114 USA. [Feghali-Bostwick, Carol] Med Univ South Carolina, Div Rheumatol & Immunol, Charleston, SC USA. [Pardo, Annie] Univ Nacl Autonoma Mexico, Mexico City, DF, Mexico. [Selman, Moises] Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico. RP Tager, AM (reprint author), Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA.; Tager, AM (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA.; Tager, AM (reprint author), Harvard Med Sch, Boston, MA 02114 USA. EM amtager@mgh.harvard.edu OI Ahluwalia, Neil/0000-0001-6262-401X FU Boehringer-Ingelheim RNAi Screening Award; National Institutes of Health [T32HL116275, P30AR061271, K24AR060297, R01HL095732, R01HL108975] FX This work was supported by Boehringer-Ingelheim RNAi Screening Award (N.A. and A.M.T.), and by National Institutes of Health grants T32HL116275 (N.A.), P30AR061271 and K24AR060297 (C.F.-B.), and R01HL095732 and R01HL108975 (A.M.T.). NR 47 TC 2 Z9 2 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1044-1549 EI 1535-4989 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JUN 1 PY 2016 VL 54 IS 6 BP 831 EP 842 DI 10.1165/rcmb.2015-0040OC PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA DT7XQ UT WOS:000381702000009 PM 26600305 ER PT J AU Naqvi, M Barth, WH AF Naqvi, Mariam Barth, William H., Jr. TI Emergency Cerclage: Outcomes, Patient Selection, and Operative Considerations SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE emergency cerclage; physical-examination indicated cerclage; emergent cerclage ID EXAM-INDICATED CERCLAGE; PEC INTERNATIONAL COHORT; CERVICAL CERCLAGE; EXPECTANT MANAGEMENT; 2ND TRIMESTER; FETAL MEMBRANES; BED REST; SHIRODKAR CERCLAGE; RESCUE CERCLAGE; WOMEN AB Emergency cerclage refers to a cerclage placed during the second trimester in a woman noted to have painless cervical dilation. Although randomized -controlled trials are limited, observational studies suggest an improvement in neonatal outcomes in selected patients undergoing an emergency cerclage. Labor and chorioamniontis are contraindications for cerclage placement. Advanced dilation (> 3 to 4 cm) and a later gestational age (22 to 24 wk) are associated with poorer outcomes. This chapter reviews the indications, outcomes and perioperative management strategies for cerclage placement in this setting. C1 [Naqvi, Mariam; Barth, William H., Jr.] Harvard Med Sch, Massachusetts Gen Hosp, Div Maternal Fetal Med, Vincent Dept Obstet & Gynecol, Founders 460, Boston, MA USA. RP Naqvi, M (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Div Maternal Fetal Med, Vincent Dept Obstet & Gynecol, Founders 460, Boston, MA USA. EM mnaqvi@partners.org NR 43 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-9201 EI 1532-5520 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD JUN PY 2016 VL 59 IS 2 BP 286 EP 294 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DS6RR UT WOS:000380910500007 PM 27101238 ER PT J AU Guan, XM Xu, MG Millar, SE Bartlett, JD AF Guan, Xiaomu Xu, Mingang Millar, Sarah E. Bartlett, John D. TI Beta-catenin is essential for ameloblast movement during enamel development SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article DE cell-cell attachment; E-cadherin; enamel; migration; beta-catenin ID TRANSCRIPTION FACTOR LEF-1; WNT/BETA-CATENIN; SECRETORY AMELOBLASTS; GENE-EXPRESSION; RAT INCISOR; MOUSE; MICE; WNT; MORPHOGENESIS; ADHESION AB Beta-catenin is a multifunctional protein that plays key roles in cadherin-based cell adherens junctions and in the Wnt signaling pathway. The canonical Wnt/beta-catenin pathway can regulate transcription factors that control cell movement/invasion. We investigated whether beta-catenin regulates ameloblast movement through canonical Wnt signaling. The morphological and physical properties of enamel were assessed in enamel from control and beta-catenin conditional knockout (cKO) mice. Ameloblast-lineage cells (ALC) were used to investigate the potential roles of beta-catenin in cell migration and in E-cadherin expression. Compared with controls, incisors from beta-catenin cKO mice were short, blunt, and where enamel was present, it was soft and malformed. Scanning electron microscopy revealed a dysplastic rod pattern within the enamel of incisors from beta-catenin cKO mice, and Vickers microhardness measurements confirmed that mice with beta-catenin ablated from their enamel organ had enamel that was significantly softer than normal. Amelogenesis was disrupted in the absence of beta-catenin and the ameloblasts did not differentiate properly. We further demonstrated that migration of ALCs was inhibited in vitro and that E-cadherin expression was significantly up-regulated when ALCs were treated with the beta-catenin inhibitor, ICG-001. Beta-catenin ablation causes enamel malformation in mice and this phenotype may occur, in part, by a lack of ameloblast differentiation and/or movement necessary to form the decussating enamel rod structure. C1 [Guan, Xiaomu] Dept Mineralized Tissue Biol, Cambridge, MA USA. [Guan, Xiaomu] Harvard Sch Dent Med, Forsyth Inst, Cambridge, MA USA. [Xu, Mingang; Millar, Sarah E.] Univ Penn, Dept Dermatol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Xu, Mingang; Millar, Sarah E.] Univ Penn, Dept Cell & Dev Biol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Bartlett, John D.] Ohio State Univ, Coll Dent, Div Biosci, Columbus, OH 43210 USA. RP Bartlett, JD (reprint author), Ohio State Univ, Coll Dent, Res Off, 4139 Postle Hall 305 W 12th Ave, Columbus, OH 43210 USA. EM bartlett.196@osu.edu FU National Institute of Dental and Craniofacial Research of the National Institutes of Health [R01DE016276, R01DE024570, R56 DE023100]; National Institutes of Health [1S10RR027553-01] FX The authors thank Dr Toshihiro Sugiyama for his generous gift of ALC cells, Dr Maiko Suzuki for help with the manuscript, and Justine Dobeck for providing mouse incisor sections and for thoughtful discussions. Research reported in this publication was supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health under award numbers R01DE016276 (JDB), R01DE024570 (SEM) and R56 DE023100 (SEM). The Forsyth Institute microCT Core is partly supported by National Institutes of Health grant 1S10RR027553-01. NR 32 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0909-8836 EI 1600-0722 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD JUN PY 2016 VL 124 IS 3 BP 221 EP 227 DI 10.1111/eos.12261 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DS0EI UT WOS:000380267800001 PM 26957367 ER PT J AU Brito-Zeron, P Kostov, B Bosch, X Acar-Denizli, N Ramos-Casals, M Stone, JH AF Brito-Zeron, Pilar Kostov, Belchin Bosch, Xavier Acar-Denizli, Nihan Ramos-Casals, Manuel Stone, John H. TI Therapeutic approach to IgG4-related disease: A systematic review SO MEDICINE LA English DT Review DE autoimmune pancreatitis; glucocorticoids; IgG4; IgG4-related disease; rituximab ID IMMUNOGLOBULIN G4-RELATED DISEASE; TYPE-1 AUTOIMMUNE PANCREATITIS; PRIMARY SCLEROSING CHOLANGITIS; SINGLE-CENTER EXPERIENCE; SERUM IGG4 LEVELS; CLINICAL-FEATURES; TUBULOINTERSTITIAL NEPHRITIS; PATHOLOGICAL CHARACTERISTICS; RETROPERITONEAL FIBROSIS; DIAGNOSTIC-CRITERIA AB To review the reported evidence on the therapeutic management of IgG4-related disease (IgG4-RD) in clinical practice.A systematic search of the literature was conducted. The primary outcome measured was the rate of efficacy of first-line therapeutic approaches. Secondary outcomes measured included the rate of disease relapse, the outcome of untreated patients, the rate of patients without drug therapy at the end of follow-up, the rate of side effects, and mortality. The MOOSE, AHRQ, STROBE, and GRACE recommendations/statements were followed.The results of the systematic search strategy yielded 62 studies that included a total of 3034 patients. Complete information about first-line therapeutic regimens was detailed in 1952 patients, including glucocorticoid-based regimens in 1437 (74%), drug-free regimens in 213 (11%), and other therapies in 38 (2%). No therapy (wait and see management) was reported in 264 (13%) patients. The efficacy of monotherapy with glucocorticoids was specified in 1220 patients, of whom 97% had a therapeutic response. Relapses, however, were reported in 464/1395 (33%) patients despite typically short follow-up periods. Therapeutic efficacy was reported in 219/231 (95%) of relapses treated with glucocorticoids, 56/69 (81%) of those treated with azathioprine, 16/22 (72%) of those treated with other immunosuppressive agents, and in the 9 cases treated with rituximab (100%). In 14 studies, the authors detailed the outcome of 159/246 patients with wait-and-see management; spontaneous improvement or resolution was reported in 68 (43%) cases. Wide heterogeneity was observed with respect to the first-line therapeutic approaches used for the different organ-specific disease subsets, including significant differences in the mean dose of glucocorticoids used.Nearly 70% of reported IgG4-RD patients are treated with oral glucocorticoids in monotherapy. However, the therapeutic management is heavily influenced by geographical, epidemiological, and clinical factors, especially with respect to the predominant organ affected. The frequency of glucocorticoid failure to induce sustained remissions both during and after treatment and the assessment of glucocorticoid toxicity in IgG4-RD require further study. C1 [Brito-Zeron, Pilar] Hosp CIMA Sanitas, Dept Med, Autoimmune Dis Unit, Barcelona, Spain. [Brito-Zeron, Pilar; Ramos-Casals, Manuel] IDIBAPS CELLEX, Sjogren Syndrome Res Grp AGAUR, Lab Autoimmune Dis Josep Font, Barcelona, Spain. [Brito-Zeron, Pilar; Ramos-Casals, Manuel] Hosp Clin Barcelona, Dept Autoimmune Dis, ICMiD, Barcelona, Spain. [Kostov, Belchin] CAPS BE, Barcelona, Spain. [Kostov, Belchin] Inst Invest Biomed August Pi & Sunyer IDIBAPS, Transverse Grp Res Primary Care, Barcelona, Spain. [Bosch, Xavier] Hosp Clin Barcelona, Dept Internal Med, ICMiD, Barcelona, Spain. [Acar-Denizli, Nihan] Mimar Sinan Fine Arts Univ, Fac Sci & Letters, Dept Stat, Istanbul, Turkey. [Ramos-Casals, Manuel] Univ Barcelona, Dept Med, Barcelona, Spain. [Stone, John H.] Harvard Med Sch, Boston, MA USA. [Stone, John H.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Ramos-Casals, M (reprint author), Hosp Clin Barcelona, Serv Malalties Autoimmunes, C Villarroel 170, E-08036 Barcelona, Spain. EM mramos@clinic.ub.es FU Grant Fondo de Investigaciones Sanitarias (MRC) [INT15/00085]; Grant "Ajut per a la Recerca Josep Font" (PBZ, Hospital Clinic-Barcelona) FX Supported by Grants Fondo de Investigaciones Sanitarias (MRC, INT15/00085) and "Ajut per a la Recerca Josep Font" (PBZ, Hospital Clinic-Barcelona 2012). NR 84 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7974 EI 1536-5964 J9 MEDICINE JI Medicine (Baltimore) PD JUN PY 2016 VL 95 IS 26 AR e4002 DI 10.1097/MD.0000000000004002 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA DS1PV UT WOS:000380369300036 PM 27368010 ER PT J AU Padwal, JA Dong, XZ Hirshman, BR Hoi-Sang, U Carter, BS Chen, CC AF Padwal, Jennifer A. Dong, Xuezhi Hirshman, Brian R. Hoi-Sang, U. Carter, Bob S. Chen, Clark C. TI Superior Efficacy of Gross Total Resection in Anaplastic Astrocytoma Patients Relative to Glioblastoma Patients SO WORLD NEUROSURGERY LA English DT Article DE Anaplastic astrocytoma; Brain tumor; Extent of resection; Glioblastoma; Glioma; SEER ID MALIGNANT GLIOMA; IDH2 MUTATIONS; UNITED-STATES; SURVIVAL; TEMOZOLOMIDE; GRADE; OUTCOMES; EXTENT; RADIOTHERAPY; POPULATION AB INTRODUCTION: Because of their relative rarity, anaplastic astrocytomas (AAs) often are grouped with glioblastomas in clinical treatment paradigms. There are reasons, however, to expect that the therapeutic response of AAs may differ from those of glioblastoma. Here, we examined the clinical benefit of gross total resection (GTR) in AA relative to glioblastoma patients. METHODS: Using the Surveillance, Epidemiology and End Results database, we identified 2755 patients with AA and patients with 21,962 glioblastoma between 1999 and 2010. Surgical resection was defined as GTR, subtotal resection (STR), biopsy only, or no resection. Kaplan-Meier curves and multivariate Cox regression were used to assess the association between GTR and survival. RESULTS: The hazard of dying from the AA was reduced in GTR patients by 40% relative to STR patients. This reduction is 59% greater than that observed in glioblastoma where GTR was associated only with a 24% reduction relative to STR (P < 0.0001). The median survival for patients with AA who underwent GTR and subtotal resection were 64 and 24 months, respectively. For glioblastoma patients, the corresponding numbers for median survival were 13 and 9 months, respectively. The survival benefit of GTR in patients with AA was particularly notable in patient age < 50, where the median survival was not reached during the study period. CONCLUSIONS: The Surveillance, Epidemiology and End Results data suggest that survival benefit associated with GTR was greater for patients with AA relative to glioblastoma patients, particularly for patients < age 50. C1 [Padwal, Jennifer A.; Dong, Xuezhi] Univ Calif San Diego, Sch Med, San Diego, CA USA. [Dong, Xuezhi] Massachusetts Gen Hosp, Codman Ctr Clin Effectiveness Surg, Boston, MA USA. [Hirshman, Brian R.; Hoi-Sang, U.; Carter, Bob S.; Chen, Clark C.] Univ Calif San Diego, Div Neurol Surg, San Diego, CA 92103 USA. RP Chen, CC (reprint author), Univ Calif San Diego, Div Neurol Surg, San Diego, CA 92103 USA. EM clarkchen@ucsd.edu NR 39 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1878-8750 EI 1878-8769 J9 WORLD NEUROSURG JI World Neurosurg. PD JUN PY 2016 VL 90 BP 186 EP 193 DI 10.1016/j.wneu.2016.02.078 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA DS1MS UT WOS:000380360500025 PM 26924115 ER PT J AU Rocque, BG AF Rocque, Brandon G. TI Neuroendoscopy for Intraventricular Tumor Resection SO WORLD NEUROSURGERY LA English DT Editorial Material ID CHILDREN C1 [Rocque, Brandon G.] Univ Alabama Birmingham, Childrens Alabama, Dept Neurosurg, Birmingham, AL USA. [Rocque, Brandon G.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Rocque, BG (reprint author), Univ Alabama Birmingham, Childrens Alabama, Dept Neurosurg, Birmingham, AL USA.; Rocque, BG (reprint author), Birmingham VA Med Ctr, Birmingham, AL USA. EM brandon.rocque@childrensal.org FU NCATS NIH HHS [KL2 TR001419, UL1 TR001417] NR 7 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 1878-8750 EI 1878-8769 J9 WORLD NEUROSURG JI World Neurosurg. PD JUN PY 2016 VL 90 BP 619 EP 620 DI 10.1016/j.wneu.2015.12.010 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA DS1MS UT WOS:000380360500080 PM 26721614 ER PT J AU Johnson, CW Johnson, R Steigman, M Odo, C Vijayan, S Tata, DV AF Johnson, Craig W. Johnson, Ronald Steigman, Michael Odo, Chioma Vijayan, Suvendra Tata, Devadatta V. TI Appropriately Targeting Group Interventions for Academic Success Adopting the Clinical Model and PAR Profiles SO EDUCATIONAL RESEARCHER LA English DT Article DE at-risk students; diversity; effect size; evaluation; measurements; performance assessment; postsecondary education; regression analyses; retention; statistics; survey research ID CORONARY-HEART-DISEASE; COLLEGE-STUDENTS; PERFORMANCE; ACHIEVEMENT; ATTRITION; EXPERIENCES; PREDICTORS; RETRIEVAL; MORTALITY; OUTCOMES AB Prevalence of academic risk (PAR) group profiles provide data enabling empirically based group-specialized prescriptions for targeted academic success interventions to increase student retention, completion, and graduation rates, while improving allocation of institutional resources. Postsecondary student attrition engenders student debt, shortages of highly trained professionals, and inadequate workforce diversity. Diagnostic PAR profiles, employing a proactive Diagnosis double right arrow Prescription double right arrow Intervention double right arrow Evaluation Model adapted from clinical medicine, enable empirically targeted, group-specialized, student-success interventions. Two-step cluster analysis of survey responses from 512 students entering first-semester urban health science community college differentiated three PAR-profile groups: (a) traditional, (b) language/education/financially challenged, and (c) older/supporting families/financially challenged. The latter two groups' end-of-first-semester odds of adverse academic status events were, respectively, 1.73 (p = .016) and 2.08 (p = .002) times the traditional group's. PAR profiles enable empirically based group-tailored interventions for increasing student retention, completion, and graduation rates, while improving allocation of institutional resources. C1 [Johnson, Craig W.; Steigman, Michael; Odo, Chioma; Vijayan, Suvendra; Tata, Devadatta V.] Univ Texas Sch Biomed Informat Houston, 7000 Fannin St,Suite 600, Houston, TX 77030 USA. [Johnson, Ronald] Univ Texas Sch Dent Houston, Houston, TX USA. [Steigman, Michael] Massachusetts Gen Hosp, LCS, 55 Fruit St, Boston, MA 02114 USA. [Vijayan, Suvendra] Univ Iowa, Coll Dent, Iowa City, IA 52242 USA. RP Johnson, CW (reprint author), Univ Texas Sch Biomed Informat Houston, 7000 Fannin St,Suite 600, Houston, TX 77030 USA. EM craig.w.johnson@uth.tmc.edu; Ronald.Johnson@uth.tmc.edu; msteigman@mgh.harvard.edu; chioma.m.odo@uth.tmc.edu; suvendrav@gmail.com; Devadatta.V.Tata@uth.tmc.edu FU Texas Higher Education Coordinating Board Minority Health Research and Education Grant Program [1799] FX This project was partially supported by Grant #1799 from the Texas Higher Education Coordinating Board Minority Health Research and Education Grant Program. NR 50 TC 0 Z9 0 U1 3 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0013-189X EI 1935-102X J9 EDUC RESEARCHER JI Educ. Researcher PD JUN-JUL PY 2016 VL 45 IS 5 BP 312 EP 323 DI 10.3102/0013189X16656939 PG 12 WC Education & Educational Research SC Education & Educational Research GA DS1DG UT WOS:000380335400005 ER PT J AU Asselin, PK Avedissian, M Knezevic, S Kornfeld, S Spungen, AM AF Asselin, Pierre K. Avedissian, Manuel Knezevic, Steven Kornfeld, Stephen Spungen, Ann M. TI Training Persons with Spinal Cord Injury to Ambulate Using a Powered Exoskeleton SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Bioengineering; Issue 112; 6MWT; ambulatory device; overground walking; paraplegia; powered exoskeleton; reciprocating gait orthosis; RGO; spinal cord injury ID RECIPROCATING GAIT ORTHOSIS; ELECTRICAL-STIMULATION; PARAPLEGIC LOCOMOTION; WALKING; PERFORMANCE; REHABILITATION; MOBILITY; CLASSIFICATION; PARAWALKER; EXERCISE AB Powered exoskeletons have become available for overground ambulation in persons with paralyses due to spinal cord injury (SCI) who have intact upper extremity function and are able to maintain upright balance using forearm crutches. To ambulate in an exoskeleton, the user must acquire the ability to maintain balance while standing, sitting and appropriate weight shifting with each step. This can be a challenging task for those with deficits in sensation and proprioception in their lower extremities. This manuscript describes screening criteria and a training program developed at the James J. Peters VA Medical Center, Bronx, NY to teach users the skills needed to utilize these devices in institutional, home or community environments. Before training can begin, potential users are screened for appropriate range of motion of the hip, knee and ankle joints. Persons with SCI are at an increased risk of sustaining lower extremity fractures, even with minimal strain or trauma, therefore a bone mineral density assessment is performed to reduce the risk of fracture. Also, as part of screening, a physical examination is performed in order to identify additional health-related contraindications. Once the person has successfully passed all screening requirements, they are cleared to begin the training program. The device is properly adjusted to fit the user. A series of static and dynamic balance tasks are taught and performed by the user before learning to walk. The person is taught to ambulate in various environments ranging from indoor level surfaces to outdoors over uneven or changing surfaces. Once skilled enough to be a candidate for home use with the exoskeleton, the user is then required to designate a companion-walker who will train alongside them. Together, the pair must demonstrate the ability to perform various advanced tasks in order to be permitted to use the exoskeleton in their home/community environment. C1 [Asselin, Pierre K.; Avedissian, Manuel; Knezevic, Steven; Spungen, Ann M.] James J Peters VA Med Ctr, Dept Vet Affairs VA, Rehabil Res & Dev Natl Ctr Excellence Med Consequ, Bronx, NY 10468 USA. [Kornfeld, Stephen] James J Peters VA Med Ctr, Dept Vet Affairs VA, Spinal Cord Injury Serv, Bronx, NY 10468 USA. RP Spungen, AM (reprint author), James J Peters VA Med Ctr, Dept Vet Affairs VA, Rehabil Res & Dev Natl Ctr Excellence Med Consequ, Bronx, NY 10468 USA. EM Ann.Spungen@va.gov FU VA Rehabilitation Research & Development National Center of Excellence for the Medical Consequences of Spinal Cord Injury (VA RRD) [B9212C] FX Support for this work was obtained by the VA Rehabilitation Research & Development National Center of Excellence for the Medical Consequences of Spinal Cord Injury (VA RR&D #B9212C). Two of the four powered exoskeleton devices were used on a loaner basis at no cost from ReWalk Robotics, Inc. (Marlborough, Massachusetts). Additionally a portion of participants obtained Orthopedic shoes which were donated by Aetrex Worldwide Inc. (Teaneck, New Jersey). NR 45 TC 0 Z9 0 U1 13 U2 14 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD JUN PY 2016 IS 112 AR e54071 DI 10.3791/54071 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DS0CX UT WOS:000380264100057 ER PT J AU Hagedorn, EJ Cillis, JL Curley, CR Patch, TC Li, B Blaser, BW Riquelme, R Zon, LI Shah, DI AF Hagedorn, Elliott J. Cillis, Jennifer L. Curley, Caitlyn R. Patch, Taylor C. Li, Brian Blaser, Bradley W. Riquelme, Raquel Zon, Leonard I. Shah, Dhvanit I. TI Generation of Parabiotic Zebrafish Embryos by Surgical Fusion of Developing Blastulae SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Developmental Biology; Issue 112; Parabiosis; Conjoined Embryos; Zebrafish; Hematopoietic Stem Cell; Zebrafish Chimera; Cell-Intrinsic and Cell-Extrinsic Functions ID HEMATOPOIETIC STEM-CELLS; GENE; EXPRESSION; CHIMERAS AB Surgical parabiosis of two animals of different genetic backgrounds creates a unique scenario to study cell-intrinsic versus cell-extrinsic roles for candidate genes of interest, migratory behaviors of cells, and secreted signals in distinct genetic settings. Because parabiotic animals share a common circulation, any blood or blood-borne factor from one animal will be exchanged with its partner and vice versa. Thus, cells and molecular factors derived from one genetic background can be studied in the context of a second genetic background. Parabiosis of adult mice has been used extensively to research aging, cancer, diabetes, obesity, and brain development. More recently, parabiosis of zebrafish embryos has been used to study the developmental biology of hematopoiesis. In contrast to mice, the transparent nature of zebrafish embryos permits the direct visualization of cells in the parabiotic context, making it a uniquely powerful method for investigating fundamental cellular and molecular mechanisms. The utility of this technique, however, is limited by a steep learning curve for generating the parabiotic zebrafish embryos. This protocol provides a step-by-step method on how to surgically fuse the blastulae of two zebrafish embryos of different genetic backgrounds to investigate the role of candidate genes of interest. In addition, the parabiotic zebrafish embryos are tolerant to heat shock, making temporal control of gene expression possible. This method does not require a sophisticated set-up and has broad applications for studying cell migration, fate specification, and differentiation in vivo during embryonic development. C1 [Hagedorn, Elliott J.; Li, Brian; Blaser, Bradley W.; Riquelme, Raquel; Zon, Leonard I.; Shah, Dhvanit I.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Hagedorn, Elliott J.; Li, Brian; Blaser, Bradley W.; Riquelme, Raquel; Zon, Leonard I.; Shah, Dhvanit I.] Harvard Med Sch, Boston, MA 02115 USA. [Cillis, Jennifer L.; Curley, Caitlyn R.; Patch, Taylor C.; Shah, Dhvanit I.] Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. [Zon, Leonard I.; Shah, Dhvanit I.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Zon, Leonard I.; Shah, Dhvanit I.] Broad Inst Massachusetts Inst Technol, Cambridge, MA 02142 USA. [Zon, Leonard I.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Blaser, Bradley W.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02215 USA. RP Shah, DI (reprint author), Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.; Shah, DI (reprint author), Harvard Med Sch, Boston, MA 02115 USA.; Shah, DI (reprint author), Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA.; Shah, DI (reprint author), Harvard Stem Cell Inst, Cambridge, MA 02138 USA.; Shah, DI (reprint author), Broad Inst Massachusetts Inst Technol, Cambridge, MA 02142 USA. EM DSHAH@research.bwh.harvard.edu OI /0000-0001-7321-776X FU American Society of Hematology; Cooley's Anemia Foundation; NIH [K01DK085217, R03DK100672, R01CA103846, P01HL032262, R01HL04880]; Taub Foundation for MDS Research; Harvard Stem Cell Institute; Cancer Research Institute; Conquer Cancer Foundation of ASCO FX We thank Julie R. Perlin for helpful comments on the manuscript. D.I.S. is supported by grants from the American Society of Hematology, the Cooley's Anemia Foundation, and the NIH (K01DK085217 and R03DK100672). E.J.H. is a Howard Hughes Medical Institute Fellow of the Helen Hay Whitney Foundation. B.L. is a Howard Hughes Medical Institute Medical Research Fellow. B.W.B. is supported by an Irvington Fellowship from the Cancer Research Institute and a Young Investigator Award from the Conquer Cancer Foundation of ASCO. L.I.Z. is supported by grants from the NIH (R01CA103846, P01HL032262, and R01HL04880), Taub Foundation for MDS Research, Harvard Stem Cell Institute, and is an investigator of the Howard Hughes Medical Institute. NR 20 TC 1 Z9 1 U1 1 U2 2 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD JUN PY 2016 IS 112 AR e54168 DI 10.3791/54168 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DS0CX UT WOS:000380264100080 ER PT J AU Kim, K Lee, H Hong, S AF Kim, Keumyeon Lee, Haeshin Hong, Seonki TI TAPE: A Biodegradable Hemostatic Glue Inspired by a Ubiquitous Compound in Plants for Surgical Application SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Bioengineering; Issue 112; Surgical glue; Polyphenols; Tannins; PEGs; Hemostasis; Biodegradable ID TANNIC-ACID; TISSUE ADHESIVES; CAPSULES; SEALANTS AB This video describes the simplest protocol for preparing biodegradable surgical glue that has an effective hemostatic ability and greater water-resistant adhesion strength than commercial tissue adhesives. Medical adhesives have attracted great attention as potential alternative tools to sutures and staples due to their convenience in usage with minimal invasiveness. Although there are several protocols for developing tissue adhesives including those commercially available such as fibrin glues and cyanoacrylate-based materials, mostly they require a series of chemical syntheses of organic molecules, or complicated protein-purification methods, in the case of bio-driven materials (i.e., fibrin glue). Also, the development of surgical glues exhibiting high adhesive properties while maintaining biodegradability is still a challenge due to difficulties in achieving good performance in the wet environment of the body. We illustrate a new method to prepare a medical glue, known as TAPE, by the weight-based separation of a water-immiscible supramolecular aggregate formed after a physical mixing of a plant-derived, wet-resistant adhesive molecule, Tannic Acid (TA), and a well-known biopolymer, Poly(Ethylene) glycol (PEG). With our approach, TAPE shows high adhesion strength, which is 2.5-fold more than commercial fibrin glue in the presence of water. Furthermore, TAPE is biodegradable in physiological conditions and can be used as a potent hemostatic glue against tissue bleeding. We expect the widespread use of TAPE in a variety of medical settings and drug delivery applications, such as polymers for muco-adhesion, drug depots, and others. C1 [Kim, Keumyeon; Lee, Haeshin] Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol, Daejeon, South Korea. [Lee, Haeshin; Hong, Seonki] Korea Adv Inst Sci & Technol, Dept Chem, Daejeon, South Korea. [Hong, Seonki] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA USA. RP Lee, H (reprint author), Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol, Daejeon, South Korea.; Lee, H; Hong, S (reprint author), Korea Adv Inst Sci & Technol, Dept Chem, Daejeon, South Korea.; Hong, S (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA USA. EM haeshin@kaist.ac.kr; Hong.Seonki@mgh.harvard.edu RI Lee, Haeshin/C-1720-2011 OI Lee, Haeshin/0000-0003-3961-9727 FU National Research Foundation of South Korea: Mid-career scientist grant [2014002855]; Ministry of Industry, Trade, and Natural Resources: World Premier Material Development Program; Center for Natureinspired Technology (CNiT) in KAIST Institute for NanoCentury (KINC) FX This study was supported by National Research Foundation of South Korea: Mid-career scientist grant (2014002855), and Ministry of Industry, Trade, and Natural Resources: World Premier Material Development Program. This work is also supported by in part by Center for Natureinspired Technology (CNiT) in KAIST Institute for NanoCentury (KINC). NR 30 TC 0 Z9 0 U1 14 U2 14 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD JUN PY 2016 IS 112 AR e53930 DI 10.3791/53930 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DS0CX UT WOS:000380264100030 ER PT J AU Betti, C Vanhoutte, I Coutuer, S De Rycke, R Mishev, K Vuylsteke, M Aesaert, S Rombaut, D Gallardo, R De Smet, F Xu, J Van Lijsebettens, M Van Breusegem, F Inze, D Rousseau, F Schymkowitz, J Russinova, E AF Betti, Camilla Vanhoutte, Isabelle Coutuer, Silvie De Rycke, Riet Mishev, Kiril Vuylsteke, Marnik Aesaert, Stijn Rombaut, Debbie Gallardo, Rodrigo De Smet, Frederik Xu, Jie Van Lijsebettens, Mieke Van Breusegem, Frank Inze, Dirk Rousseau, Frederic Schymkowitz, Joost Russinova, Eugenia TI Sequence-Specific Protein Aggregation Generates Defined Protein Knockdowns in Plants SO PLANT PHYSIOLOGY LA English DT Article ID AMYLOID-LIKE FIBRILS; CELL-DIVISION; BRASSINOSTEROID BIOSYNTHESIS; GSK3-LIKE KINASES; TRANSGENIC PLANTS; BUILDING-BLOCKS; ARABIDOPSIS; MAIZE; GENE; GROWTH AB Protein aggregation is determined by short (5-15 amino acids) aggregation-prone regions (APRs) of the polypeptide sequence that self-associate in a specific manner to form beta-structured inclusions. Here, we demonstrate that the sequence specificity of APRs can be exploited to selectively knock down proteins with different localization and function in plants. Synthetic aggregation-prone peptides derived from the APRs of either the negative regulators of the brassinosteroid (BR) signaling, the glycogen synthase kinase 3/Arabidopsis SHAGGY-like kinases (GSK3/ASKs), or the starch-degrading enzyme alpha-glucan water dikinase were designed. Stable expression of the APRs in Arabidopsis (Arabidopsis thaliana) and maize (Zea mays) induced aggregation of the target proteins, giving rise to plants displaying constitutive BR responses and increased starch content, respectively. Overall, we show that the sequence specificity of APRs can be harnessed to generate aggregation-associated phenotypes in a targeted manner in different subcellular compartments. This study points toward the potential application of induced targeted aggregation as a useful tool to knock down protein functions in plants and, especially, to generate beneficial traits in crops. C1 [Betti, Camilla; Vanhoutte, Isabelle; Coutuer, Silvie; De Rycke, Riet; Mishev, Kiril; Aesaert, Stijn; Rombaut, Debbie; Van Lijsebettens, Mieke; Van Breusegem, Frank; Inze, Dirk; Russinova, Eugenia] VIB, Dept Plant Syst Biol, B-9052 Ghent, Belgium. [Betti, Camilla; Vanhoutte, Isabelle; Coutuer, Silvie; De Rycke, Riet; Mishev, Kiril; Aesaert, Stijn; Rombaut, Debbie; Van Lijsebettens, Mieke; Van Breusegem, Frank; Inze, Dirk; Russinova, Eugenia] Univ Ghent, Dept Plant Biotechnol & Bioinformat, B-9052 Ghent, Belgium. [Gallardo, Rodrigo; De Smet, Frederik; Xu, Jie; Rousseau, Frederic] VIB, SWITCH Lab, B-3000 Leuven, Belgium. [Gallardo, Rodrigo; De Smet, Frederik; Xu, Jie; Rousseau, Frederic; Schymkowitz, Joost] Univ Leuven, Dept Cellular & Mol Med, SWITCH Lab, B-3000 Leuven, Belgium. [Vuylsteke, Marnik] Gnomixx, B-9000 Ghent, Belgium. [Coutuer, Silvie] Bekintex Bekaert NV, B-8000 Brugge, Belgium. [Mishev, Kiril] Bulgarian Acad Sci, Inst Plant Physiol & Genet, BU-1113 Sofia, Bulgaria. [De Smet, Frederik] MIT, Dana Farber Canc Inst, Cambridge, MA 02141 USA. [De Smet, Frederik] MIT, Broad Inst, Cambridge, MA 02141 USA. [Xu, Jie] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med,State Key Lab Oncogenes & Related Genes, Shanghai Inst Digest Dis,Div Gastroenterol & Hepa, Shanghai 200001, Peoples R China. RP Russinova, E (reprint author), VIB, Dept Plant Syst Biol, B-9052 Ghent, Belgium.; Russinova, E (reprint author), Univ Ghent, Dept Plant Biotechnol & Bioinformat, B-9052 Ghent, Belgium.; Rousseau, F (reprint author), VIB, SWITCH Lab, B-3000 Leuven, Belgium.; Rousseau, F; Schymkowitz, J (reprint author), Univ Leuven, Dept Cellular & Mol Med, SWITCH Lab, B-3000 Leuven, Belgium. EM frederic.rousseau@switch.vib-kuleuven.be; joost.schymkowitz@switch.vib-kuleuven.be; eugenia.russinova@psb.vib-ugent.be RI De Smet, Frederik/Q-7808-2016; Rousseau, Frederic/J-9044-2016; OI De Smet, Frederik/0000-0002-6669-3335; Rousseau, Frederic/0000-0002-9189-7399; Gallardo, Rodrigo/0000-0003-1584-3564; Betti, Camilla/0000-0003-3522-6440 FU Agency for Innovation by Science and Technology ("Strategisch Basisonderzoek") [60839]; Ghent University ("Industrieel Onderzoeksfonds") [F2014/IOF-StarrTT261]; Ghent University (Multidisciplinary Research Partnership "Biotechnology for a Sustainable Economy") [01MRB510W]; Research Foundation-Flanders (Joint Project Bulgarian Academy of Sciences) [VS.025.13N]; Interuniversity Attraction Poles Program [IUAP VII/29]; Belgian State, Science Policy Office, University of Leuven; European Research Council under the European Union's Horizon Framework Programme (ERC) [647458] FX This work was supported by grants from the Agency for Innovation by Science and Technology ("Strategisch Basisonderzoek" project no. 60839), Ghent University ("Industrieel Onderzoeksfonds" F2014/IOF-StarrTT261 and Multidisciplinary Research Partnership "Biotechnology for a Sustainable Economy" no. 01MRB510W), the Research Foundation-Flanders (Joint Project Bulgarian Academy of Sciences VS.025.13N), the Interuniversity Attraction Poles Program (IUAP VII/29), initiated by the Belgian State, Science Policy Office, University of Leuven, and the European Research Council under the European Union's Horizon 2020 Framework Programme (ERC Grant agreement 647458). NR 69 TC 1 Z9 1 U1 5 U2 10 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 EI 1532-2548 J9 PLANT PHYSIOL JI Plant Physiol. PD JUN PY 2016 VL 171 IS 2 BP 773 EP 787 DI 10.1104/pp.16.00335 PG 15 WC Plant Sciences SC Plant Sciences GA DS3RA UT WOS:000380699200004 PM 27208282 ER PT J AU Coroller, TP Agrawal, V Narayan, V Hou, Y Grossmann, P Lee, SW Mak, RH Aerts, HJWL AF Coroller, Thibaud P. Agrawal, Vishesh Narayan, Vivek Hou, Ying Grossmann, Patrick Lee, Stephanie W. Mak, Raymond H. Aerts, Hugo J. W. L. TI Radiomic phenotype features predict pathological response in non-small cell lung cancer SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Radiomics; Pathological response; NSCLC; Biomarkers; Quantitative imaging ID RANDOMIZED CONTROLLED-TRIAL; GROSS TUMOR VOLUME; NEOADJUVANT THERAPY; PROGNOSTIC-FACTOR; SURVIVAL MODELS; FDG-PET; CHEMOTHERAPY; TEXTURE; RADIOTHERAPY; VARIABILITY AB Background and purpose: Radiomics can quantify tumor phenotype characteristics non-invasively by applying advanced imaging feature algorithms. In this study we assessed if pre-treatment radiomics data are able to predict pathological response after neoadjuvant chemoradiation in patients with locally advanced non-small cell lung cancer (NSCLC). Materials and Methods: 127 NSCLC patients were included in this study. Fifteen radiomic features selected based on stability and variance were evaluated for its power to predict pathological response. Predictive power was' evaluated using area under the curve (AUC). Conventional imaging features (tumor volume and diameter) were used for comparison. Results: Seven features were predictive for pathologic gross residual disease (AUC > 0.6, p-value < 0.05), and one for pathologic complete response (AUC = 0.63, p-value = 0.01). No conventional imaging features were predictive (range AUC = 0.51-0.59, p-value > 0.05). Tumors that did not respond well to neoadjuvant chemoradiation were more likely to present a rounder shape (spherical disproportionality, AUC = 0.63, p-value = 0.009) and heterogeneous texture (LoG 5 mm 3D - GLCM entropy, AUC = 0.61, p-value = 0.03). Conclusion: We identified predictive radiomic features for pathological response, although no conventional features were significantly predictive. This study demonstrates that radiomics can provide valuable clinical information, and performed better than conventional imaging features. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Coroller, Thibaud P.; Agrawal, Vishesh; Narayan, Vivek; Hou, Ying; Grossmann, Patrick; Lee, Stephanie W.; Mak, Raymond H.; Aerts, Hugo J. W. L.] Harvard Med Sch, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA USA. [Aerts, Hugo J. W. L.] Harvard Med Sch, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiol, Boston, MA USA. RP Coroller, TP (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dana Farber Canc Inst, 450 Brookline Ave,JF518, Boston, MA 02115 USA. EM tcoroller@lroc.harvard.edu RI Aerts, Hugo/P-6350-2015; OI Aerts, Hugo/0000-0002-2122-2003; Coroller, Thibaud/0000-0001-7662-8724 FU National Institutes of Health (NIH-USA) [U24CA194354, U01CA190234]; Kaye Scholar Award; Brigham and Women's Hospital Department of Radiation Oncology Clinical Translational Grant FX Authors acknowledge financial support from the National Institutes of Health (NIH-USA U24CA194354, and NIH-USA U01CA190234). This project was partially funded by the Kaye Scholar Award and the Brigham and Women's Hospital Department of Radiation Oncology Clinical Translational Grant. NR 38 TC 7 Z9 8 U1 4 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD JUN PY 2016 VL 119 IS 3 BP 480 EP 486 DI 10.1016/j.radonc.2016.04.004 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DR7JH UT WOS:000380075400017 PM 27085484 ER PT J AU Rasmussen, DD Johanson, SS Kincaid, CL AF Rasmussen, D. D. Johanson, S. S. Kincaid, C. L. TI MELATONIN TREATMENT DURING ALCOHOL WITHDRAWAL AND PROTRACTED DEPRIVATION REVERSES RAT THYROID HORMONE DYSREGULATION: CORRELATION WITH STARTLE RESPONSE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 25-29, 2016 CL New Orleans, LA SP Res Soc Alcoholism C1 [Rasmussen, D. D.; Johanson, S. S.; Kincaid, C. L.] VA Puget Sound HCS, Mental Hlth Serv, VISN MIRECC 20, Seattle, WA 98108 USA. [Rasmussen, D. D.; Johanson, S. S.; Kincaid, C. L.] Univ Washington, Dept Psychiat, Seattle, WA 98108 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2016 VL 40 SU 1 SI SI MA 078 BP 35A EP 35A PG 1 WC Substance Abuse SC Substance Abuse GA DR3PH UT WOS:000379814601078 ER PT J AU Dou, X Mitsuyama, R Charness, ME AF Dou, X. Mitsuyama, R. Charness, M. E. TI ANKYRIN-G BINDING TO L1 REGULATES L1 SENSITIVITY TO ETHANOL BY INSIDE-OUT SIGNALING SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 25-29, 2016 CL New Orleans, LA SP Res Soc Alcoholism ID CELL-ADHESION MOLECULE; INHIBITION C1 VA Boston Healthcare Syst, West Roxbury, MA 02132 USA. Harvard Med Sch, West Roxbury, MA 02132 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2016 VL 40 SU 1 SI SI MA 570 BP 158A EP 158A PG 1 WC Substance Abuse SC Substance Abuse GA DR3PH UT WOS:000379814601568 ER PT J AU McDonald, J Pennington, DL Lasher, B Yohannes, S Wong, T Bielenberg, J Dack, J Tomlinson, E Hoyman, L Kinzler, A Batki, SL AF McDonald, J. Pennington, D. L. Lasher, B. Yohannes, S. Wong, T. Bielenberg, J. Dack, J. Tomlinson, E. Hoyman, L. Kinzler, A. Batki, S. L. TI AN EXAMINATION OF MEDICAL COMORBIDITIES AND CIGARETTE USE AMONG VETERANS WITH ALCOHOL USE DISORDER AND COMORBID PTSD SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 25-29, 2016 CL New Orleans, LA SP Res Soc Alcoholism C1 Univ Calif San Francisco, San Francisco Vet Adm Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2016 VL 40 SU 1 SI SI MA 581 BP 161A EP 161A PG 1 WC Substance Abuse SC Substance Abuse GA DR3PH UT WOS:000379814601579 ER PT J AU Batki, SL Pennington, DL Lasher, B Yohannes, S McDonald, J Kinzler, A Bielenberg, J Dack, J Tomlinson, E Hoyman, L Herbst, E Wong, T AF Batki, S. L. Pennington, D. L. Lasher, B. Yohannes, S. McDonald, J. Kinzler, A. Bielenberg, J. Dack, J. Tomlinson, E. Hoyman, L. Herbst, E. Wong, T. TI TOPIRAMATE TREATMENT FOR ALCOHOL USE DISORDER IN VETERANS WITH MILD TRAUMATIC BRAIN INJURY: PRELIMINARY RESULTS OF A PILOT CONTROLLED CLINICAL TRIAL SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 25-29, 2016 CL New Orleans, LA SP Res Soc Alcoholism C1 Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA 94121 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2016 VL 40 SU 1 SI SI MA 588 BP 162A EP 162A PG 1 WC Substance Abuse SC Substance Abuse GA DR3PH UT WOS:000379814601586 ER PT J AU Yohannes, S Pennington, DL Lasher, B Wong, T McDonald, J Dack, J Bielenberg, J Hoyman, LC Tomlinson, ES Kinzler, A Herbst, E Batki, SL AF Yohannes, S. Pennington, D. L. Lasher, B. Wong, T. McDonald, J. Dack, J. Bielenberg, J. Hoyman, L. C. Tomlinson, E. S. Kinzler, A. Herbst, E. Batki, S. L. TI EDUCATION PREDICTS ATTENDANCE AND RETENTION IN A RANDOMISED TRIAL OF TOPIRMATE TREATMENT FOR VETERANS WITH AUD AND PTSD SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 25-29, 2016 CL New Orleans, LA SP Res Soc Alcoholism C1 Univ Calif San Francisco, San Francisco Vet Adm Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2016 VL 40 SU 1 SI SI MA 587 BP 162A EP 162A PG 1 WC Substance Abuse SC Substance Abuse GA DR3PH UT WOS:000379814601585 ER PT J AU Pennington, DL Tomlinson, ES Lasher, B Yohannes, S Wong, T McDonald, J Dack, J Bielenberg, J Hoyman, LC Kinzler, A AF Pennington, D. L. Tomlinson, E. S. Lasher, B. Yohannes, S. Wong, T. McDonald, J. Dack, J. Bielenberg, J. Hoyman, L. C. Kinzler, A. TI ASSOCIATIONS OF PTSD, AUD, AND TBI SEVERITY ON COGNITIVE FUNCTION IN VETERANS ENTERING CONTROLLED TRIALS OF TOPIRAMATE TREATMENT SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 25-29, 2016 CL New Orleans, LA SP Res Soc Alcoholism C1 Univ Calif San Francisco, San Francisco Vet Adm Med Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2016 VL 40 SU 1 SI SI MA 589 BP 163A EP 163A PG 1 WC Substance Abuse SC Substance Abuse GA DR3PH UT WOS:000379814601587 ER PT J AU Kinzler, A Pennington, DL Lasher, B Yohannes, S McDonald, J Wong, T Bielenberg, J Dack, J Tomlinson, E Hoyman, L Herbst, E Batki, SL AF Kinzler, A. Pennington, D. L. Lasher, B. Yohannes, S. McDonald, J. Wong, T. Bielenberg, J. Dack, J. Tomlinson, E. Hoyman, L. Herbst, E. Batki, S. L. TI ABSORPTION SUBTYPE OF DISTRESS TOLERANCE PREDICTS DRINKING BEHAVIOR IN VETERANS WITH AUD AND PTSD SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 25-29, 2016 CL New Orleans, LA SP Res Soc Alcoholism C1 Univ Calif San Francisco, San Francisco Vet Adm Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2016 VL 40 SU 1 SI SI MA 611 BP 168A EP 168A PG 1 WC Substance Abuse SC Substance Abuse GA DR3PH UT WOS:000379814601609 ER PT J AU Fallah-Sohy, N Vilsaint, CL Cristello, JV O'Connor, CL Jason, LA Stout, RL Kelly, JF AF Fallah-Sohy, N. Vilsaint, C. L. Cristello, J. V. O'Connor, C. L. Jason, L. A. Stout, R. L. Kelly, J. F. TI CHARACTERIZATION OF ADDICTION RECOVERY COMMUNITY CENTERS IN THE NORTHEASTERN UNITED STATES SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 25-29, 2016 CL New Orleans, LA SP Res Soc Alcoholism C1 [Fallah-Sohy, N.; Vilsaint, C. L.; Cristello, J. V.; O'Connor, C. L.; Jason, L. A.; Stout, R. L.; Kelly, J. F.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2016 VL 40 SU 1 SI SI MA 683 BP 186A EP 186A PG 1 WC Substance Abuse SC Substance Abuse GA DR3PH UT WOS:000379814601681 ER PT J AU Kelly, JF Yeterian, JD Cristello, J Kaminer, Y Kahler, C Timko, C AF Kelly, J. F. Yeterian, J. D. Cristello, J. Kaminer, Y. Kahler, C. Timko, C. TI DEVELOPING AND TESTING TWELVE-STEP FACILITATION FOR ADOLESCENTS WITH SUBSTANCE USE DISORDER: MANUAL DEVELOPMENT AND PRELIMINARY OUTCOMES SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 25-29, 2016 CL New Orleans, LA SP Res Soc Alcoholism C1 [Kelly, J. F.; Yeterian, J. D.; Cristello, J.; Kaminer, Y.; Kahler, C.; Timko, C.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Recovery Res Inst, 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2016 VL 40 SU 1 SI SI MA 682 BP 186A EP 186A PG 1 WC Substance Abuse SC Substance Abuse GA DR3PH UT WOS:000379814601680 ER PT J AU Rasmussen, DD Johanson, SS Burns, JN Kincaid, CL AF Rasmussen, D. D. Johanson, S. S. Burns, J. N. Kincaid, C. L. TI REDUCTION OF alpha 1-AND beta-ADRENERGIC SIGNALING AT THE TIME OF TRAUMATIC STRESS REDUCES SUBSEQUENT DEVELOPMENT OF INCREASED ALCOHOL DRINKING IN RATS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 25-29, 2016 CL New Orleans, LA SP Res Soc Alcoholism C1 VA Puget Sound HCS, Mental Hlth Serv, VISN MIRECC 20, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat, Seattle, WA 98108 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2016 VL 40 SU 1 SI SI MA 729 BP 198A EP 198A PG 1 WC Substance Abuse SC Substance Abuse GA DR3PH UT WOS:000379814601727 ER PT J AU Oot, EN Sawyer, KS Jensen, JE Luhar, RB Oscar-Berman, M Silveri, MM AF Oot, E. N. Sawyer, K. S. Jensen, J. E. Luhar, R. B. Oscar-Berman, M. Silveri, M. M. TI ASSOCIATIONS OF ANTERIOR CINGULATE METABOLITE LEVELS WITH NEUROPSYCHOLOGICAL MEASURES IN ALCOHOLISM: THE ROLE OF GENDER SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 25-29, 2016 CL New Orleans, LA SP Res Soc Alcoholism C1 [Oot, E. N.; Sawyer, K. S.; Jensen, J. E.; Luhar, R. B.; Oscar-Berman, M.; Silveri, M. M.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Oot, E. N.; Sawyer, K. S.; Jensen, J. E.; Luhar, R. B.; Oscar-Berman, M.; Silveri, M. M.] McLean Hosp, McLean Imaging Ctr, Belmont, MA 02478 USA. [Oot, E. N.; Sawyer, K. S.; Jensen, J. E.; Luhar, R. B.; Oscar-Berman, M.; Silveri, M. M.] 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2016 VL 40 SU 1 SI SI MA 800 BP 215A EP 215A PG 1 WC Substance Abuse SC Substance Abuse GA DR3PH UT WOS:000379814601798 ER PT J AU Cristello, JV Vilsaint, CL O'Connor, CL Kelly, NW Kelly, JF AF Cristello, J. V. Vilsaint, C. L. O'Connor, C. L. Kelly, N. W. Kelly, J. F. TI CROSS-VALIDATION OF THE TIMELINE FOLLOWBACK (TLFB; FORM 90) AND WEEKLY SUBSTANCE USE FORM (WSUF) AMONG TREATED ADOLESCENTS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 25-29, 2016 CL New Orleans, LA SP Res Soc Alcoholism C1 [Cristello, J. V.; Vilsaint, C. L.; O'Connor, C. L.; Kelly, N. W.; Kelly, J. F.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Addict Med, 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2016 VL 40 SU 1 SI SI MA 867 BP 232A EP 232A PG 1 WC Substance Abuse SC Substance Abuse GA DR3PH UT WOS:000379814601865 ER PT J AU Vilsaint, CL Kelly, JF Groshkova, T Best, D White, W AF Vilsaint, C. L. Kelly, J. F. Groshkova, T. Best, D. White, W. TI DEVELOPMENT OF A 10 ITEM ASSESSMENT OF ALCOHOL AND DRUG USE DISORDER RECOVERY CAPITAL (ARC-10) USING ITEM RESPONSE THEORY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 25-29, 2016 CL New Orleans, LA SP Res Soc Alcoholism C1 [Vilsaint, C. L.; Kelly, J. F.; Groshkova, T.; Best, D.; White, W.] Harvard Med Sch, 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2016 VL 40 SU 1 SI SI MA 869 BP 233A EP 233A PG 1 WC Substance Abuse SC Substance Abuse GA DR3PH UT WOS:000379814601867 ER PT J AU Bergman, BG Sylvia, EJ Kelly, JF AF Bergman, B. G. Sylvia, E. J. Kelly, J. F. TI THE ASSOCIATION BETWEEN ALCOHOL USE DISORDER AND SOCIAL NETWORK SITE ENGAGEMENT AMONG TREATMENT SEEKING EMERGING ADULTS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 25-29, 2016 CL New Orleans, LA SP Res Soc Alcoholism C1 Harvard Med Sch, Massachusetts Gen Hosp, Recovery Res Inst, 151 Merrimac St, Boston, MA 02114 USA. Addict Recovery Management Serv, 151 Merrimac St, Boston, MA 02114 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2016 VL 40 SU 1 SI SI MA 879 BP 235A EP 235A PG 1 WC Substance Abuse SC Substance Abuse GA DR3PH UT WOS:000379814601877 ER PT J AU Anderson, RI Lopez, MF Becker, HC AF Anderson, R. I. Lopez, M. F. Becker, H. C. TI MODELING STRESS-INDUCED ETHANOL CONSUMPTION IN MICE WITH A HISTORY OF CHRONIC INTERMITTENT ETHANOL EXPOSURE: INVOLVEMENT OF CRF AND DYNORPHIN SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 25-29, 2016 CL New Orleans, LA SP Res Soc Alcoholism C1 [Anderson, R. I.; Lopez, M. F.; Becker, H. C.] Med Univ South Carolina, Charleston, SC 29425 USA. [Anderson, R. I.; Lopez, M. F.; Becker, H. C.] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2016 VL 40 SU 1 SI SI MA 010 BP 250A EP 250A PG 1 WC Substance Abuse SC Substance Abuse GA DR3PH UT WOS:000379814602010 ER PT J AU Bergman, BG Hoeppner, BB Nelson, LM Slaymaker, V Kelly, JF AF Bergman, B. G. Hoeppner, B. B. Nelson, L. M. Slaymaker, V. Kelly, J. F. TI THE EFFECTS OF PROFESSIONAL AND 12-STEP MUTUAL-HELP CONTINUING CARE ON EMERGING ADULT RESIDENTIAL TREATMENT OUTCOMES SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 25-29, 2016 CL New Orleans, LA SP Res Soc Alcoholism C1 Massachusetts Gen Hosp, Recovery Res Inst, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA 02114 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2016 VL 40 SU 1 SI SI MA 076 BP 266A EP 266A PG 1 WC Substance Abuse SC Substance Abuse GA DR3PH UT WOS:000379814602076 ER PT J AU Dou, X Mitsuyama, R Charness, ME AF Dou, X. Mitsuyama, R. Charness, M. E. TI REGULATION OF ETHANOL INHIBITION OF L1 ADHESION BY PHOSPHORYLATION OF THE L1 CYTOPLASMIC DOMAIN SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 25-29, 2016 CL New Orleans, LA SP Res Soc Alcoholism C1 VA Boston Healthcare Syst, West Roxbury, MA 02115 USA. Harvard Med Sch, West Roxbury, 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2016 VL 40 SU 1 SI SI MA 195 BP 297A EP 297A PG 1 WC Substance Abuse SC Substance Abuse GA DR3PH UT WOS:000379814602195 ER PT J AU Kelly, JF Cristello, J Yeterian, JD Kaminer, Y Kahler, CW Timko, C AF Kelly, J. F. Cristello, J. Yeterian, J. D. Kaminer, Y. Kahler, C. W. Timko, C. TI FINDINGS FROM THE FIRST RANDOMIZED CONTROLLED TRIAL OF ADOLESCENT TWELVE-STEP FACILITATION SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 25-29, 2016 CL New Orleans, LA SP Res Soc Alcoholism C1 [Kelly, J. F.; Cristello, J.; Yeterian, J. D.] Mass Gen Hosp, Boston, MA 02114 USA. [Kaminer, Y.] Univ Connecticut, Farmington, CT 06030 USA. [Kahler, C. W.] Brown Univ, Providence, RI 02912 USA. [Timko, C.] Stanford Univ, Menlo Pk, CA 94025 USA. [Timko, C.] VA Menlo Pk, Menlo Pk, CA 94025 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2016 VL 40 SU 1 SI SI MA 237 BP 307A EP 307A PG 1 WC Substance Abuse SC Substance Abuse GA DR3PH UT WOS:000379814602237 ER PT J AU Fallah-Sohy, N AF Fallah-Sohy, N. TI CLNIICAL AND PUBLIC HEALTH UTILITY OF RECOVERY COMMUNITY CENTERS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) CY JUN 25-29, 2016 CL New Orleans, LA SP Res Soc Alcoholism C1 [Fallah-Sohy, N.] Massachusetts Gen Hosp, Ctr Addict Med, 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2016 VL 40 SU 1 SI SI MA 255 BP 312A EP 312A PG 1 WC Substance Abuse SC Substance Abuse GA DR3PH UT WOS:000379814602255 ER PT J AU Jena, AB Blumenthal, DM Stevens, W Chou, JW Ton, TGN Goldman, DP AF Jena, Anupam B. Blumenthal, Daniel M. Stevens, Warren Chou, Jacquelyn W. Ton, Thanh G. N. Goldman, Dana P. TI Value of Improved Lipid Control in Patients at High Risk for Adverse Cardiac Events SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; RANDOMIZED-TRIALS; STATISTICAL LIFE; VASCULAR-DISEASE; LDL CHOLESTEROL; STATIN THERAPY; HEART-DISEASE; METAANALYSIS AB Objectives: Lipid-lowering therapy (LLT) is suboptimally used in patients with hyperlipidemia in the 2 highest statin benefit groups (SBGs), as categorized by the American College of Cardiology and the American Heart Association. This study estimated the social value of reducing low-density lipoprotein cholesterol (LDL-C) levels by 50% for patients in SBGs 1 and 2 who have been treated with standard LLT but have not reached LDL-C goal, as well as the potential value of PCSK9 inhibitors for patients in these groups. Study Design: Simulation model. Methods: We used National Health and Nutrition Examination Surveys (NHANES) and US Census data to project the population of SBGs 1 and 2 in the time period 2015 to 2035. We used insurance claims data to estimate incidence rates of major adverse cardiac events (MACEs), and NHANES with National Vital Statistics data to estimate cardiovascular disease mortality rates. Using established associations between LDL-C and MACE risk, we estimated the value of reducing LDL-C levels by 50%. We incorporated results from a meta-analysis to estimate the value of PSCK9 inhibitors. Results: Among those treated with LLT with LDL-C >70 mg/dL in SBGs 1 and 2, the cumulative value of reducing LDL-C levels by 50% would be $2.9 trillion from 2015 to 2035, resulting primarily from 1.6 million deaths averted. The cumulative value of PCSK9 inhibitors would range from $3.4 trillion to $5.1 trillion (1.9-2.8 million deaths averted), or $12,000 to $17,000 per patient-year of treatment. Conclusions: Lowering LDL-C in high-risk patients with hyperlipidemia has enormous potential social value. For patients in these high-risk groups, PCSK9 inhibitors may have considerable net value depending on the final prices payers ultimately select. C1 [Jena, Anupam B.; Blumenthal, Daniel M.] Harvard Med Sch, Boston, MA USA. [Jena, Anupam B.; Blumenthal, Daniel M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stevens, Warren; Chou, Jacquelyn W.; Ton, Thanh G. N.] Precis Hlth Econ, Oakland, CA USA. [Goldman, Dana P.] Univ Southern Calif, Los Angeles, CA USA. RP Jena, AB (reprint author), Harvard Med Sch, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM Jena@hcp.med.harvard.edu FU Amgen, Thousand Oaks, CA FX Funding for this research was provided by Amgen, Thousand Oaks, CA. NR 43 TC 1 Z9 1 U1 0 U2 2 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JUN PY 2016 VL 22 IS 6 BP E199 EP + PG 23 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DR9VX UT WOS:000380245300003 PM 27355907 ER PT J AU Khullar, D Rao, SK Chaguturu, SK Rajkumar, R AF Khullar, Dhruv Rao, Sandhya K. Chaguturu, Sreekanth K. Rajkumar, Rahul TI The Evolving Role of Subspecialties in Population Health Management and New Healthcare Delivery Models SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Editorial Material ID MEDICAL NEIGHBORHOOD; SAFETY-NET; SPECIALISTS AB New healthcare delivery models, including accountable care organizations (ACOs) and patient-centered medical homes, emphasize a more robust role for primary care. However, it is less clear how the roles and responsibilities of subspecialists should change as we enter a new paradigm of alternative payment models. Health systems seeking to better manage population health and control costs will need a clearer understanding of how best to incorporate subspecialty practitioners: What is a subspecialist's role? How does it vary by subspecialty? How should they be compensated? We argue that subspecialist compensation in ACOs and other new care delivery models should recognize the range of ways in which specialists can provide value to patients across a population-which varies depending on the provider's role in a patient's care. Only by more thoughtfully engaging, equipping, and compensating subspecialty practitioners can we achieve reform's central goal of better population health at a lower cost. C1 [Khullar, Dhruv; Rao, Sandhya K.; Chaguturu, Sreekanth K.] Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. [Chaguturu, Sreekanth K.] Partners HealthCare, Populat Hlth Management, Boston, MA USA. [Rajkumar, Rahul] Ctr Medicare Serv, Washington, DC USA. [Rajkumar, Rahul] Ctr Medicaid Serv, Washington, DC USA. RP Khullar, D (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM dkhullar@partners.org NR 8 TC 0 Z9 0 U1 4 U2 4 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JUN PY 2016 VL 22 IS 6 BP E192 EP E195 PG 4 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DR9VX UT WOS:000380245300001 PM 27355905 ER PT J AU Ljuboja, D Powers, BW Robbins, B Huckman, R Yeshwant, K Jain, SH AF Ljuboja, Damir Powers, Brian W. Robbins, Benjamin Huckman, Robert Yeshwant, Krishna Jain, Sachin H. TI When Doctors Go to Business School: Career Choices of Physician-MBAs SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Editorial Material AB There has been substantial growth in the number of physicians pursing Master of Business Administration (MBA) degrees over the past decade, but there is continuing debate over the utility of these programs and the career outcomes of their graduates. The authors analyzed the clinical and professional activities of a large cohort of physician-MBAs by gathering information on 206 physician graduates from the Harvard Business School MBA program who obtained their degrees between 1941 and 2014. Key outcome measures that were examined include medical specialty, current professional activity, and clinical practice. Chi square tests were used to assess the correlations in the data. Among the careers that were tracked (n = 195), there was significant heterogeneity in current primary employment. The most common sectors were clinical (27.7%), investment banking/finance (27.0%), hospital/provider administration (11.7%), biotech/device/pharmaceutical (10.9%), and entrepreneurship (9.5%). Overall, 84% of physician-MBAs entered residency; approximately half (49.3%) remained clinically active in some capacity and only one-fourth (27.7%) reported clinical medicine as their primary professional role. Among those who pursued residency training, the most common specialties were internal medicine (39.3%), emergency medicine (10.4%), orthopedic surgery (9.2%), and general surgery (8.6%). Physician-MBAs trained in internal medicine were significantly more likely to remain clinically active (63.8% vs 42.4%; P = .01). Clinical activity and primary employment in a clinical role decreased after degree conferment. After completing their education, a majority of physician-MBAs divert their primary professional focus away from clinical activity. These findings reveal new insights into the career outcomes of physician-MBAs. C1 [Ljuboja, Damir; Powers, Brian W.] Harvard Med Sch, Boston, MA USA. [Ljuboja, Damir; Powers, Brian W.; Huckman, Robert] Harvard Sch Business, Boston, MA USA. [Robbins, Benjamin; Yeshwant, Krishna] Google Ventures, Boston, MA USA. [Robbins, Benjamin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Robbins, Benjamin] McLean Hosp, 115 Mill St, Belmont, MA 02178 USA. [Yeshwant, Krishna] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Jain, Sachin H.] CareMore Hlth Syst, 12900 Pk Plaza Dr,Ste 150, Cerritos, CA 90703 USA. [Jain, Sachin H.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. RP Jain, SH (reprint author), CareMore Hlth Syst, 12900 Pk Plaza Dr,Ste 150, Cerritos, CA 90703 USA. EM sachin.jain@caremore.com NR 5 TC 0 Z9 0 U1 3 U2 3 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JUN PY 2016 VL 22 IS 6 BP E196 EP E198 PG 3 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DR9VX UT WOS:000380245300002 PM 27355906 ER PT J AU Melnitchouk, SI Sundt, TM AF Melnitchouk, Serguei I. Sundt, Thoralf M., III TI How would I treat? THE INVITED EXPERTS' OPINION SO EUROINTERVENTION LA English DT Editorial Material C1 [Melnitchouk, Serguei I.; Sundt, Thoralf M., III] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Melnitchouk, SI (reprint author), Cox 630,55 Fruit St, Boston, MA 02114 USA. EM smelnitchouk@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU EUROPA EDITION PI TOULOUSE CEDEX 6 PA 19 ALLEES JEAN JAURES B P 61508, TOULOUSE CEDEX 6, 31015, FRANCE SN 1774-024X EI 1969-6213 J9 EUROINTERVENTION JI EuroIntervention PD JUN PY 2016 VL 12 IS 3 BP 411 EP 411 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DR7MF UT WOS:000380083100026 ER PT J AU Fartaria, MJ Bonnier, G Roche, A Kober, T Meuli, R Rotzinger, D Frackowiak, R Schluep, M Du Pasquier, R Thiran, JP Krueger, G Cuadra, MB Granziera, C AF Fartaria, Mario Joao Bonnier, Guillaume Roche, Alexis Kober, Tobias Meuli, Reto Rotzinger, David Frackowiak, Richard Schluep, Myriam Du Pasquier, Renaud Thiran, Jean-Philippe Krueger, Gunnar Cuadra, Meritxell Bach Granziera, Cristina TI Automated Detection of White Matter and Cortical Lesions in Early Stages of Multiple Sclerosis SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article ID CONSENSUS GUIDELINES; BRAIN MRI; SEGMENTATION; CLASSIFICATION AB Purpose: To develop a method to automatically detect multiple sclerosis (MS) lesions, located both in white matter (WM) and in the cortex, in patients with low disability and early disease stage. Materials and Methods: We developed a lesion detection method, based on the k-nearest neighbor (k-NN) technique, to detect lesions as small as 0.0036 mL. This method uses the image intensity information from up to four different 3D magnetic resonance imaging (MRI) sequences (magnetization-prepared rapid gradient-echo, MPRAGE; magnetization-prepared two inversion-contrast rapid gradient-echo, MP2RAGE; 3D fluid-attenuated inversion recovery, FLAIR; and 3D double-inversion recovery, DIR), acquired on a 3T scanner. To these intensity features we added the information obtained by the spatial coordinates and tissue prior probabilities provided by the International Consortium for Brain Mapping (ICBM). Quantitative assessment was done in 39 early-stage MS patients with a "leave-one-out" cross-validation. Results: The best lesion detection rate (DR) performance in WM was obtained using MP2RAGE, FLAIR, and DIR intensities (77% for lesions >= 0.0036 mL; 85% for lesions >= 0.005 mL). Similar results were obtained excluding the DIR intensity as well as when using only MPRAGE and FLAIR (DR575%, P = 0.5720). However, the combination of FLAIR with DIR and MP2RAGE appeared to be the best for detecting cortical lesions (DR = 62%), compared to the other combination of sequences (P < 0.001). Conclusion: For WM lesion detection, similar results were observed when only conventional clinical sequences (FLAIR, MPRAGE) were used compared to a combination of conventional and "advanced" sequences (MP2RAGE, DIR). Cortical lesion detection increased significantly when "advanced" sequences were used. C1 [Fartaria, Mario Joao; Bonnier, Guillaume; Roche, Alexis; Kober, Tobias; Granziera, Cristina] Siemens Healthcare AG, Adv Clin Imaging Technol HC CMEA BM PI, Lausanne, Switzerland. [Fartaria, Mario Joao; Bonnier, Guillaume; Roche, Alexis; Kober, Tobias; Thiran, Jean-Philippe; Krueger, Gunnar; Cuadra, Meritxell Bach] Ecole Polytech Fed Lausanne, Signal Proc Lab LTS5, Lausanne, Switzerland. [Bonnier, Guillaume; Granziera, Cristina] CHU Vaudois, Dept Clin Neurosci, Lab Rech Neuroimagerie LREN, Lausanne, Switzerland. [Bonnier, Guillaume; Roche, Alexis; Kober, Tobias; Meuli, Reto; Rotzinger, David; Frackowiak, Richard; Schluep, Myriam; Du Pasquier, Renaud; Thiran, Jean-Philippe; Cuadra, Meritxell Bach; Granziera, Cristina] Univ Lausanne UNIL, Lausanne, Switzerland. [Roche, Alexis; Kober, Tobias; Meuli, Reto; Rotzinger, David; Thiran, Jean-Philippe; Cuadra, Meritxell Bach] CHU Vaudois, Dept Radiol, Lausanne, Switzerland. [Frackowiak, Richard; Granziera, Cristina] CHU Vaudois, Dept Clin Neurosci, Lausanne, Switzerland. [Schluep, Myriam; Du Pasquier, Renaud] CHU Vaudois, Dept Clin Neurosci, Neuroimmunol Unit, Neurol, Lausanne, Switzerland. [Krueger, Gunnar] Siemens Med Solut USA Inc, Boston, MA USA. [Cuadra, Meritxell Bach] Ctr Imagerie BioMed CIBM, Signal Proc Core, Lausanne, Switzerland. [Granziera, Cristina] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Chalestown, MA USA. [Granziera, Cristina] Harvard Med Sch, Chalestown, MA USA. RP Fartaria, MJ (reprint author), Siemens Healthcare AG, Adv Clin Imaging Technol HC CMEA BM PI, Lausanne, Switzerland. EM mario.fartaria_de_oliveira@siemens.com; mario.fartaria_de_oliveira@siemens.com RI Du Pasquier, Renaud/O-8588-2016; Centre d'imagerie Biomedicale, CIBM/B-5740-2012; OI Du Pasquier, Renaud/0000-0002-2786-3434; Roche, Alexis/0000-0002-4821-6893; Granziera, Cristina/0000-0002-4917-8761 FU Swiss National Science Foundation [PZ00P3_131914/11]; Swiss Government: Federal Commission for Scholarships for Foreign Students (FCS); Swiss MS Society; Societe Academique Vaudoise; Centre d'Imagerie Bio-Medicale (CIBM) of the University of Lausanne (UNIL); Swiss Federal Institute of Technology Lausanne (EPFL); University of Geneva (UniGe); Centre Hospitalier Universitaire Vaudois (CHUV); Hopitaux Universitaires de Geneve (HUG); Leenaards Foundation; Jeantet Foundation FX Contract grant sponsor: Swiss National Science Foundation; Contract grant number: PZ00P3_131914/11; Contract grant sponsor: Swiss Government: Federal Commission for Scholarships for Foreign Students (FCS); Contract grant sponsor: Swiss MS Society and the Societe Academique Vaudoise; Contract grant sponsor: Centre d'Imagerie Bio-Medicale (CIBM) of the University of Lausanne (UNIL); Contract grant sponsor: Swiss Federal Institute of Technology Lausanne (EPFL); Contract grant sponsor: University of Geneva (UniGe); Contract grant sponsor: Centre Hospitalier Universitaire Vaudois (CHUV); Contract grant sponsor: Hopitaux Universitaires de Geneve (HUG); Contract grant sponsor: Leenaards and the Jeantet Foundations NR 46 TC 2 Z9 2 U1 5 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 EI 1522-2586 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JUN PY 2016 VL 43 IS 6 BP 1445 EP 1454 DI 10.1002/jmri.25095 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DR7FY UT WOS:000380066600020 PM 26606758 ER PT J AU Jalian, HR Levin, Y Wanner, M AF Jalian, H. Ray Levin, Yakir Wanner, Molly TI Physical modalities for treating acne and rosacea SO SEMINARS IN CUTANEOUS MEDICINE AND SURGERY LA English DT Article ID PULSED-DYE-LASER; RANDOMIZED CONTROLLED-TRIAL; INFLAMMATORY FACIAL ACNE; ALUMINUM-GARNET LASER; 1,450-NM DIODE-LASER; ACID CHEMICAL PEELS; SPLIT-FACE TRIAL; ND-YAG LASER; PHOTODYNAMIC THERAPY; GLYCOLIC ACID AB Physical modalities provide an important adjunct to medical treatment of acne and rosacea. In patients who cannot tolerate or fail medical treatments, physical modalities offer an alternative approach. For cases of acne scarring, phymatous changes of rosacea, and rosacea-associated telangiectasia, physical modalities such as laser and light treatments represent the treatment of choice. We will review the use of laser and light treatments, photodynamic therapy, and other physical modalities such as targeted therapies for the treatment of acne and rosacea. (C) 2016 Frontline Medical Communications C1 [Levin, Yakir; Wanner, Molly] Massachusetts Gen Hosp, Harvard Med Sch, Dept Dermatol, Boston, MA 02114 USA. RP Wanner, M (reprint author), 50 Staniford St,Suite 200, Boston, MA 02118 USA. EM mwanner@partners.org NR 74 TC 0 Z9 0 U1 8 U2 8 PU FRONTLINE MEDICAL COMMUNICATIONS PI THE WOODLANDS PA WRIGHTS MEDIA, 2407 TIMBERLOCH PLACE, SUITE B, THE WOODLANDS, TX 77386 USA SN 1085-5629 EI 1558-0768 J9 SEMIN CUTAN MED SURG JI Semin. Cutan. Med. Surg. PD JUN PY 2016 VL 35 IS 2 BP 96 EP 102 DI 10.12788/j.sder.2016.028 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA DR8YC UT WOS:000380183300009 PM 27416315 ER PT J AU Reis, FCG Branquinho, JLO Brandao, BB Guerra, BA Silva, ID Frontini, A Thomou, T Sartini, L Cinti, S Kahn, CR Festuccia, WT Kowaltowski, AJ Mori, MA AF Reis, Felipe C. G. Branquinho, Jessica L. O. Brandao, Bruna B. Guerra, Beatriz A. Silva, Ismael D. Frontini, Andrea Thomou, Thomas Sartini, Loris Cinti, Saverio Kahn, C. Ronald Festuccia, William T. Kowaltowski, Alicia J. Mori, Marcelo A. TI Fat-specific Dicer deficiency accelerates aging and mitigates several effects of dietary restriction in mice SO AGING-US LA English DT Article DE dicer; adipose tissue; aging; dietary restriction; insulin resistance ID ADIPOSE-TISSUE; INSULIN-RESISTANCE; CALORIE RESTRICTION; AMINO-ACIDS; MICRORNA; OBESITY; STRESS; METABOLISM; ADIPOCYTES; EXPRESSION AB Aging increases the risk of type 2 diabetes, and this can be prevented by dietary restriction (DR). We have previously shown that DR inhibits the downregulation of miRNAs and their processing enzymes - mainly Dicer - that occurs with aging in mouse white adipose tissue (WAT). Here we used fat-specific Dicer knockout mice (AdicerKO) to understand the contributions of adipose tissue Dicer to the metabolic effects of aging and DR. Metabolomic data uncovered a clear distinction between the serum metabolite profiles of Lox control and AdicerKO mice, with a notable elevation of branched-chain amino acids (BCAA) in AdicerKO. These profiles were associated with reduced oxidative metabolism and increased lactate in WAT of AdicerKO mice and were accompanied by structural and functional changes in mitochondria, particularly under DR. AdicerKO mice displayed increased mTORC1 activation in WAT and skeletal muscle, where Dicer expression is not affected. This was accompanied by accelerated age-associated insulin resistance and premature mortality. Moreover, DR-induced insulin sensitivity was abrogated in AdicerKO mice. This was reverted by rapamycin injection, demonstrating that insulin resistance in AdicerKO mice is caused by mTORC1 hyperactivation. Our study evidences a DR-modulated role for WAT Dicer in controlling metabolism and insulin resistance. C1 [Reis, Felipe C. G.; Branquinho, Jessica L. O.; Brandao, Bruna B.; Guerra, Beatriz A.; Mori, Marcelo A.] Univ Fed Sao Paulo, Dept Biophys, Escola Paulista Med, Sao Paulo, Brazil. [Silva, Ismael D.] Univ Fed Sao Paulo, Dept Gynecol, Escola Paulista Med, Sao Paulo, Brazil. [Frontini, Andrea] Univ Pavia, Dept Publ Hlth Expt & Forens Med, Pavia, Italy. [Thomou, Thomas; Kahn, C. Ronald] Harvard Med Sch, Sect Integrat Physiol & Metab, Joslin Diabet Ctr, Boston, MA 02215 USA. [Sartini, Loris; Cinti, Saverio] Univ Politecn Marche, Dept Clin & Expt Med, Ancona, Italy. [Festuccia, William T.] Univ Sao Paulo, Inst Ciencias Biomed, Dept Physiol, Sao Paulo, Brazil. [Kowaltowski, Alicia J.] Univ Sao Paulo, Inst Quim, Dept Biochem, Sao Paulo, Brazil. [Mori, Marcelo A.] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, Campinas, SP, Brazil. RP Mori, MA (reprint author), Univ Fed Sao Paulo, Dept Biophys, Escola Paulista Med, Sao Paulo, Brazil.; Mori, MA (reprint author), Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, Campinas, SP, Brazil. EM morima@unicamp.br OI Gomes dos Reis, Felipe/0000-0001-8357-5261; Festuccia, William/0000-0003-4769-0806 FU FAPESP [2010/52557-0, 2015/01316-7, 2011/24109-6]; CNPq; CAPES FX This study was supported by grants of FAPESP (2010/52557-0, 2015/01316-7, and 2011/24109-6), CNPq and CAPES. NR 55 TC 0 Z9 0 U1 3 U2 6 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1945-4589 J9 AGING-US JI Aging-US PD JUN PY 2016 VL 8 IS 6 BP 1201 EP 1222 DI 10.18632/aging.100970 PG 22 WC Cell Biology SC Cell Biology GA DR8VY UT WOS:000380177700007 PM 27241713 ER PT J AU Sawyer, KS Oscar-Berman, M Ruiz, SM Galvez, DA Makris, N Harris, GJ Valera, EM AF Sawyer, Kayle S. Oscar-Berman, Marlene Ruiz, Susan Mosher Galvez, Daniel A. Makris, Nikos Harris, Gordon J. Valera, Eve M. TI Associations Between Cerebellar Subregional Morphometry and Alcoholism History in Men and Women SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol; Magnetic Resonance Imaging; Gender; Cerebellum; Brain; Volume ID ANATOMICALLY SPECIFIED METHOD; FUNCTIONAL TOPOGRAPHY; DEPENDENT PATIENTS; DRINKING HISTORY; LIMB MOVEMENTS; RATING-SCALE; BRAIN; DEFICITS; VOLUME; MRI AB Background: Alcoholism has been linked to deficits in cognitive, behavioral, and emotional functions, and the cerebellum is important for optimal functioning of these abilities. However, little is known about how individual differences such as gender and drinking history might influence regional cerebellar abnormalities. Methods: Volumetric analyses of the cerebellum and its subregions were performed in relation to the interaction of gender and measures of drinking history. Structural magnetic resonance imaging scans of 44 alcoholic individuals (23 men) and 39 nonalcoholic controls (18 men) were obtained. In addition to measuring total cerebellar gray and white matter volumes, we measured 64 individual cerebellar parcellation units, as well as functionally defined a priori regions of interest that have been shown to correspond to functions impaired in alcoholism. Results: Total cerebellar white matter volume was smaller in alcoholic relative to nonalcoholic participants. Moreover, volumes of parcellation units varied with drinking history, showing negative associations between years of heavy drinking and the anterior lobe, the vestibulocerebellar lobe, and the spinocerebellar subdivision. The negative association between anterior volume and years of heavy drinking was driven primarily by alcoholic men. Additionally, we observed larger white and gray matter volumes for alcoholic women than for alcoholic men. Conclusions: The identification of drinking-related abnormalities in cerebellar subregions lays a foundation that can be utilized to inform how cerebro-cerebellar networks are perturbed in this pathological condition. These results also provide estimates of how gender and individual differences in drinking history can predict cerebellar volumes. C1 [Sawyer, Kayle S.; Oscar-Berman, Marlene] Boston Univ, Sch Med, PhD Program Behav Neurosci, Grad Med Sci, Boston, MA 02118 USA. [Sawyer, Kayle S.; Oscar-Berman, Marlene; Ruiz, Susan Mosher] VA Boston Healthcare Syst, Boston, MA USA. [Sawyer, Kayle S.; Oscar-Berman, Marlene; Ruiz, Susan Mosher; Makris, Nikos; Harris, Gordon J.; Valera, Eve M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Boston, MA 02114 USA. [Oscar-Berman, Marlene; Ruiz, Susan Mosher] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Galvez, Daniel A.] Boston Univ, Coll Arts & Sci, Boston, MA 02215 USA. [Makris, Nikos] Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA. [Makris, Nikos] Harvard Med Sch, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA USA. [Harris, Gordon J.] Massachusetts Gen Hosp, Dept Radiol, Radiol Comp Aided Diagnost Lab, Boston, MA USA. [Harris, Gordon J.; Valera, Eve M.] Harvard Med Sch, Dept Radiol, Massachusetts Gen Hosp, Boston, MA USA. RP Sawyer, KS (reprint author), Dept Vet Affairs Healthcare Syst, 150 South Huntington Ave,151A, Boston, MA 02130 USA. EM kslays@bu.edu OI Sawyer, Kayle/0000-0001-7767-5688 FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [R01AA07112, K05AA00219]; U.S. Department of Veterans Affairs Clinical Science Research and Development grant; National Institute of Child Health and Human Development grant [R01HD067744]; Center for Functional Neuroimaging Technologies grant from the National Center for Research Resources [P41RR14075] FX This work was supported by funds from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) grants R01AA07112 and K05AA00219, and by the U.S. Department of Veterans Affairs Clinical Science Research and Development grant to MO-B, by funds from National Institute of Child Health and Human Development grant R01HD067744 to EVM, as well as by the Center for Functional Neuroimaging Technologies grant P41RR14075 from the National Center for Research Resources. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. The authors thank Mary M. Valmas, Diane Merritt, Pooja Parikh, Riya B. Luhar, and Zoe Gravitz for recruitment assistance and neuropsychological testing, EmilyKate McDonough for assistance with the figures, Brianne Campbell for manual labeling, and George Papadimitriou for data processing. The authors declare no conflict of interests. NR 55 TC 0 Z9 0 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2016 VL 40 IS 6 BP 1262 EP 1272 DI 10.1111/acer.13074 PG 11 WC Substance Abuse SC Substance Abuse GA DR3OA UT WOS:000379811300013 PM 27130832 ER PT J AU Levine, AJ Ting, DT Greenbaum, BD AF Levine, Arnold J. Ting, David T. Greenbaum, Benjamin D. TI P53 and the defenses against genome instability caused by transposons and repetitive elements SO BIOESSAYS LA English DT Article DE cancer biology; cancer immunology; endogenous elements; genome stability; innate immunity; repetitive elements; transposons ID TUMOR-SUPPRESSOR PROTEIN; NONCODING RNAS; CANCER-CELLS; SOMATIC RETROTRANSPOSITION; ENDOGENOUS RETROVIRUSES; INTERFERON RESPONSE; METHYLATION CAUSES; DNA METHYLATION; GENE-REGULATION; HUMAN BRAIN AB The recent publication by Wylie et al. is reviewed, demonstrating that the p53 protein regulates the movement of transposons. While this work presents genetic evidence for a piRNA-mediated p53 interaction with transposons in Drosophila and zebrafish, it is herein placed in the context of a decade or so of additional work that demonstrated a role for p53 in regulating transposons and other repetitive elements. The line of thought in those studies began with the observation that transposons damage DNA and p53 regulates DNA damage. The presence of transposon movement can increase the rate of evolution in the germ line and alter genes involved in signal transduction pathways. Transposition can also play an important role in cancers where the p53 gene function is often mutated. This is particularly interesting as recent work has shown that de-repression of repetitive elements in cancer has important consequences for the immune system and tumor microenvironment. C1 [Levine, Arnold J.] Inst Adv Study, Sch Nat Sci, Simons Ctr Syst Biol, Olden Lane, Princeton, NJ 08540 USA. [Levine, Arnold J.] Rutgers Canc Inst New Jersey, New Brunswick, NJ 08903 USA. [Ting, David T.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Ting, David T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Greenbaum, Benjamin D.] Icahn Sch Med Mt Sinai, Dept Med Hematol & Med Oncol & Pathol, Tisch Canc Inst, New York, NY 10029 USA. RP Levine, AJ (reprint author), Inst Adv Study, Sch Nat Sci, Simons Ctr Syst Biol, Olden Lane, Princeton, NJ 08540 USA.; Levine, AJ (reprint author), Rutgers Canc Inst New Jersey, New Brunswick, NJ 08903 USA. EM alevine@ias.edu OI Ting, David/0000-0002-3261-2322 FU NIH [P01CA087497-13, K12CA087723-11A1]; Stand Up to Cancer; V Foundation; Burroughs Wellcome Trust FX The authors would like thank Nina Bhardwaj, Ahmet Denil, John Rinn, and Scott Younger for reading our manuscript and for their helpful comments. We would ike to acknowledge the support of NIH P01CA087497-13 (AJL, BDG), Stand Up to Cancer (DTT, BDG), the V Foundation (DTT, BDG), Burroughs Wellcome Trust (DTT), and NIH K12CA087723-11A1 (DTT). NR 57 TC 3 Z9 3 U1 6 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0265-9247 EI 1521-1878 J9 BIOESSAYS JI Bioessays PD JUN PY 2016 VL 38 IS 6 BP 508 EP 513 DI 10.1002/bies.201600031 PG 6 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA DR6ZC UT WOS:000380048800004 PM 27172878 ER PT J AU Jakubowiak, A Raje, N Vij, R Reece, D Berdeja, J Vesole, D Jagannath, S Cole, C Faham, M Nam, J Stephens, L Severson, E Revethis, A Wolfe, B Rosebeck, S Gurbuxani, S Rosenbaum, C Jasielec, J Dytfeld, D Griffith, K Zimmerman, T AF Jakubowiak, A. Raje, N. Vij, R. Reece, D. Berdeja, J. Vesole, D. Jagannath, S. Cole, C. Faham, M. Nam, J. Stephens, L. Severson, E. Revethis, A. Wolfe, B. Rosebeck, S. Gurbuxani, S. Rosenbaum, C. Jasielec, J. Dytfeld, D. Griffith, K. Zimmerman, T. TI IMPROVED EFFICACY AFTER INCORPORATING AUTOLOGOUS STEM CELL TRANSPLANT (ASCT) INTO KRD TREATMENT WITH CARFILZOMIB (CFZ), LENALIDOMIDE (LEN), AND DEXAMETHASONE (DEX) IN NEWLY DIAGNOSED MULTIPLE MYELOMA SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Jakubowiak, A.; Nam, J.; Stephens, L.; Severson, E.; Revethis, A.; Wolfe, B.; Rosebeck, S.; Gurbuxani, S.; Rosenbaum, C.; Zimmerman, T.] Univ Chicago, Chicago, IL 60637 USA. [Raje, N.] Massachussetts Gen Hosp, Boston, MA USA. [Vij, R.] Washington Univ, St Louis, MO USA. [Reece, D.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Berdeja, J.] Sarah Cannon Res Inst, Nashville, TN USA. [Vesole, D.] John Theurer Canc Ctr, Hackensack, NJ USA. [Jagannath, S.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Cole, C.; Griffith, K.] Univ Michigan, Ann Arbor, MI 48109 USA. [Faham, M.] Adapt Biotechnol, Seattle, WA USA. [Jasielec, J.] Northshore Univ Hlth Syst, Evanston, IL USA. [Dytfeld, D.] NJ Univ Med Sci, Poznan, Poland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA S101 BP 1 EP 2 PG 2 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600003 ER PT J AU McCarthy, PL Palumbo, A Holstein, SA Lauwers-Cances, V Petrucci, MT Richardson, PG Hulin, C Tosi, P Anderson, KC Caillot, D Magarotto, V Moreau, P Marit, G Yu, Z Attal, M AF McCarthy, P. L. Palumbo, A. Holstein, S. A. Lauwers-Cances, V. Petrucci, M. T. Richardson, P. G. Hulin, C. Tosi, P. Anderson, K. C. Caillot, D. Magarotto, V. Moreau, P. Marit, G. Yu, Z. Attal, M. TI A META-ANALYSIS OF OVERALL SURVIVAL IN PATIENTS WITH MULTIPLE MYELOMA TREATED WITH LENALIDOMIDE MAINTENANCE AFTER HIGH-DOSE MELPHALAN AND AUTOLOGOUS STEM CELL TRANSPLANT SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [McCarthy, P. L.] Roswell Pk Canc Inst, Blood & Marrow Transplant Program, Buffalo, NY 14263 USA. [McCarthy, P. L.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Palumbo, A.; Magarotto, V.] Univ Turin, Turin, Italy. [Holstein, S. A.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Lauwers-Cances, V.; Attal, M.] Hop Purpan, Dept Hematol, Toulouse, France. [Lauwers-Cances, V.; Attal, M.] Hop Purpan, Dept Biostat, Toulouse, France. [Petrucci, M. T.] Univ Roma La Sapienza, Rome, Italy. [Richardson, P. G.; Anderson, K. C.] Harvard Med Sch, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA USA. [Hulin, C.] Bordeaux Hosp Univ Ctr CHU, Bordeaux, France. [Tosi, P.] Univ Bologna, Seragnoli Inst Hematol & Med Oncol, Bologna, Italy. [Caillot, D.] Univ Dijon, Ctr Hosp, Dijon, France. [Moreau, P.] Univ Hosp, Hotel Dieu, Nantes, France. [Marit, G.] Ctr Hosp Univ, Bordeaux, France. [Yu, Z.] Celgene Corp, Summit, NJ USA. RI richard, chrystelle/K-8595-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA S103 BP 2 EP 3 PG 2 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600005 ER PT J AU Jabbour, EJ Advani, AS Stelljes, M Stock, W Liedtke, M Goekbuget, N Martinelli, G O'Brien, S Wang, K Wang, T Paccagnella, ML Sleight, B Vandendries, E DeAngelo, DJ Kantarjian, HM AF Jabbour, E. J. Advani, A. S. Stelljes, M. Stock, W. Liedtke, M. Goekbuget, N. Martinelli, G. O'Brien, S. Wang, K. Wang, T. Paccagnella, M. L. Sleight, B. Vandendries, E. DeAngelo, D. J. Kantarjian, H. M. TI EFFICACY AND SAFETY OF INOTUZUMAB OZOGAMICIN IN OLDER PATIENTS WITH RELAPSED/REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA ENROLLED IN THE GLOBAL PHASE 3 RANDOMIZED CONTROLLED INO-VATE TRIAL SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Jabbour, E. J.; Kantarjian, H. M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Advani, A. S.] Cleveland Clin Main Campus, Cleveland, OH USA. [Stelljes, M.] Univ Klinikum Munster, Munster, Germany. [Stock, W.] Univ Chicago, Chicago, IL 60637 USA. [Liedtke, M.] Stanford Canc Inst, Stanford, CA USA. [Goekbuget, N.] Goethe Univ, Frankfurt, Germany. [Martinelli, G.] Univ Bologna, Bologna, Italy. [O'Brien, S.] Univ Calif Irvine, Orange, CA 92668 USA. [Wang, K.] Pfizer Inc, Pearl River, NY USA. [Wang, T.; Paccagnella, M. L.; Sleight, B.] Pfizer Inc, Groton, CT 06340 USA. [Vandendries, E.] Pfizer Inc, Cambridge, MA USA. [DeAngelo, D. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P167 BP 32 EP 32 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600069 ER PT J AU Wang, E Stone, R Tallman, M Thompson, J Ontiveros, E Olson, G Galinsky, I Pond, B Uchida, A Urity, V Xhori, O Macaraeg, M Vusirikala, M Patel, P Walter, R Collins, R AF Wang, E. Stone, R. Tallman, M. Thompson, J. Ontiveros, E. Olson, G. Galinsky, I. Pond, B. Uchida, A. Urity, V. Xhori, O. Macaraeg, M. Vusirikala, M. Patel, P. Walter, R. Collins, R. TI SAFETY STUDY OF CRENOLANIB, A TYPE I FLT3 INHIBITOR, WITH CYTARABINE/DAUNORUBICIN OR CYTARABINE/IDARUBICIN INDUCTION AND HIGH-DOSE CYTARABINE CONSOLIDATION IN NEWLY DIAGNOSED FLT3+AML SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Wang, E.; Thompson, J.; Ontiveros, E.; Olson, G.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Stone, R.; Galinsky, I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tallman, M.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Pond, B.; Vusirikala, M.; Patel, P.; Collins, R.] Univ Texas Southwestern, New York, NY USA. [Uchida, A.; Urity, V.; Xhori, O.; Macaraeg, M.] Arog Pharmaceut Inc, Dallas, TX USA. [Walter, R.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P186 BP 41 EP 41 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600089 ER PT J AU DeAngelo, DJ O'Dwyer, ME Becker, PS Liesveld, JL Bixby, DL Magnani, JL Thackray, HM Jonas, BA AF DeAngelo, D. J. O'Dwyer, M. E. Becker, P. S. Liesveld, J. L. Bixby, D. L. Magnani, J. L. Thackray, H. M. Jonas, B. A. TI RESULTS OF A PHASE I STUDY OF GMI-1271, A NOVEL E-SELECTIN ANTAGONIST IN COMBINATION WITH INDUCTION CHEMOTHERAPY IN RELAPSED/REFRACTORY AML: A NOVEL, WELL-TOLERATED REGIMEN WITH A HIGH REMISSION RATE SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [DeAngelo, D. J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [O'Dwyer, M. E.] Natl Univ Ireland, Dept Haematol, Galway, Ireland. [Becker, P. S.] Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA. [Liesveld, J. L.] Univ Rochester, Med Ctr, Dept Med, Hematol Oncol, Rochester, NY 14627 USA. [Bixby, D. L.] Univ Michigan, Dept Internal Med, Div Hematol & Oncol, Ann Arbor, MI 48109 USA. [Magnani, J. L.; Thackray, H. M.] GlycoMimetics, Rockville, MD USA. [Jonas, B. A.] Univ Calif Davis, Ctr Comprehens Canc, Dept Med, Div Hematol & Oncol, Sacramento, CA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P191 BP 43 EP 44 PG 2 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600094 ER PT J AU Pollyea, DA Di Nardo, C Thirman, M Letai, A Wei, A Jonas, BA Arellano, M Frattini, M Kantarjian, H Chyla, B Zhu, M Potluri, J Humerickhouse, R Mabry, M Konopleva, M Pratz, K AF Pollyea, D. A. Di Nardo, C. Thirman, M. Letai, A. Wei, A. Jonas, B. A. Arellano, M. Frattini, M. Kantarjian, H. Chyla, B. Zhu, M. Potluri, J. Humerickhouse, R. Mabry, M. Konopleva, M. Pratz, K. TI RESULTS OF A PHASE 1B STUDY OF VENETOCLAX PLUS DECITABINE OR AZACITIDINE IN UNTREATED ACUTE MYELOID LEUKEMIA PATIENTS >= 65 YEARS INELIGIBLE FOR STANDARD INDUCTION THERAPY SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Pollyea, D. A.] Univ Colorado, Sch Med, Aurora, England. [Di Nardo, C.; Kantarjian, H.; Konopleva, M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Thirman, M.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Letai, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wei, A.] Alfred Hosp, Melbourne, Vic, Australia. [Wei, A.] Monash Univ, Melbourne, Vic, Australia. [Jonas, B. A.] Univ Calif Davis, Ctr Comprehens Canc, Sacramento, CA USA. [Arellano, M.] Emory Univ, Atlanta, GA 30322 USA. [Frattini, M.] Columbia Univ, Med Ctr, New York, NY USA. [Chyla, B.; Zhu, M.; Potluri, J.; Humerickhouse, R.; Mabry, M.] AbbVie Inc, N Chicago, IL USA. [Pratz, K.] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. NR 0 TC 2 Z9 2 U1 4 U2 5 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P192 BP 44 EP 44 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600095 ER PT J AU Rosenblat, T Heaney, M Jurcic, J Raza, A Harwood, K Djaballah, H Scandura, J Letai, A Frattini, M AF Rosenblat, T. Heaney, M. Jurcic, J. Raza, A. Harwood, K. Djaballah, H. Scandura, J. Letai, A. Frattini, M. TI A PHASE I TRIAL OF A PHARMACODYNAMICALLY-CONCEIVED DECITABINE/THIOGUANINE COMBINATION IN PATIENTS WITH ADVANCED MYELOID MALIGNANCIES SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Rosenblat, T.; Heaney, M.; Jurcic, J.; Raza, A.; Harwood, K.; Frattini, M.] Columbia Univ, Med Ctr, New York, NY USA. [Djaballah, H.] Inst Pasteur Korea, Seoul, South Korea. [Scandura, J.] Weill Cornell Sch Med, New York, NY USA. [Letai, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P193 BP 44 EP 44 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600096 ER PT J AU Pavlasova, G Borsky, M Seda, V Cerna, K Osickova, J Doubek, M Mayer, J Calogero, R Pospisilova, S Davids, M Brown, J Mraz, M AF Pavlasova, G. Borsky, M. Seda, V. Cerna, K. Osickova, J. Doubek, M. Mayer, J. Calogero, R. Pospisilova, S. Davids, M. Brown, J. Mraz, M. TI IBRUTINIB INHIBITS CD20 UP-REGULATION ON CLL B CELLS MEDIATED BY THE CXCR4/SDF-1 AXIS SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Pavlasova, G.; Seda, V.; Cerna, K.; Osickova, J.; Pospisilova, S.; Mraz, M.] CEITEC MU, Mol Med, Brno, Czech Republic. [Pavlasova, G.; Borsky, M.; Seda, V.; Cerna, K.; Osickova, J.; Doubek, M.; Mayer, J.; Pospisilova, S.; Mraz, M.] Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic. [Pavlasova, G.; Borsky, M.; Seda, V.; Cerna, K.; Osickova, J.; Doubek, M.; Mayer, J.; Pospisilova, S.; Mraz, M.] Fac Med MU, Brno, Czech Republic. [Calogero, R.] Univ Turin, Dept Biotechnol & Hlth Sci, Turin, Italy. [Davids, M.; Brown, J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RI Mraz, Marek/E-1774-2012 NR 0 TC 0 Z9 0 U1 2 U2 2 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P200 BP 47 EP 47 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600103 ER PT J AU Roberts, AW Ma, S Brander, D Kipps, TJ Barrientos, JC Davids, MS Anderson, MA Choi, M Tam, C Lash, LL Verdugo, M Kim, SY Zhu, M Seymour, JF AF Roberts, A. W. Ma, S. Brander, D. Kipps, T. J. Barrientos, J. C. Davids, M. S. Anderson, M. A. Choi, M. Tam, C. Lash, L. L. Verdugo, M. Kim, S. Y. Zhu, M. Seymour, J. F. TI IMPACT OF ADDING RITUXIMAB TO VENETOCLAX ON THE RATE, QUALITY, AND DURATION OF RESPONSE IN PATIENTS WITH RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKAEMIA: A CROSS-STUDY MULTIVARIABLE ANALYSIS SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Roberts, A. W.; Anderson, M. A.] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Roberts, A. W.] Walter & Eliza Hall Inst Med Res, Canc & Hematol Div, Melbourne, Vic, Australia. [Ma, S.] Northwestern Univ, Chicago, IL 60611 USA. [Brander, D.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Kipps, T. J.; Choi, M.] Univ Calif San Diego, San Diego, CA 92103 USA. [Barrientos, J. C.] Hofstra Northwell Sch Med, Hempstead, NY USA. [Davids, M. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tam, C.; Seymour, J. F.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Lash, L. L.; Verdugo, M.; Kim, S. Y.; Zhu, M.] AbbVie Inc, N Chicago, IL USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P209 BP 51 EP 52 PG 2 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600112 ER PT J AU Davids, MS Kim, HT Bsat, J Savell, A Francoeur, K Hellman, JM Brander, DM Jacobson, CA Hochberg, EP Takvorian, RW Abramson, JS Fisher, DC Brown, JR AF Davids, M. S. Kim, H. T. Bsat, J. Savell, A. Francoeur, K. Hellman, J. M. Brander, D. M. Jacobson, C. A. Hochberg, E. P. Takvorian, R. W. Abramson, J. S. Fisher, D. C. Brown, J. R. TI PRELIMINARY RESULTS OF A PHASE II STUDY OF IBRUTINIB IN COMBINATION WITH FCR (IFCR) IN PREVIOUSLY UNTREATED, YOUNGER PATIENTS WITH CLL SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Davids, M. S.; Kim, H. T.; Bsat, J.; Savell, A.; Francoeur, K.; Hellman, J. M.; Jacobson, C. A.; Fisher, D. C.; Brown, J. R.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Brander, D. M.] Duke Univ, Med Ctr, Med Oncol, Durham, NC 27706 USA. [Hochberg, E. P.; Takvorian, R. W.; Abramson, J. S.] Massachusetts Gen Hosp, Med Oncol, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P210 BP 52 EP 52 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600113 ER PT J AU Robak, T Jones, J Wach, M Brown, J Menter, A Vandenberghe, E Ysebaert, L Wagner-Johnston, N Polikoff, J Awan, F Badoux, X Coutre, S Spurgeon, S Loscertales, J Xing, G Dubowy, R Flinn, I Owen, C AF Robak, T. Jones, J. Wach, M. Brown, J. Menter, A. Vandenberghe, E. Ysebaert, L. Wagner-Johnston, N. Polikoff, J. Awan, F. Badoux, X. Coutre, S. Spurgeon, S. Loscertales, J. Xing, G. Dubowy, R. Flinn, I. Owen, C. TI UPDATED RESULTS OF A PHASE 3 RANDOMIZED, CONTROLLED STUDY OF IDELALISIB IN COMBINATION WITH OFATUMUMAB FOR PREVIOUSLY TREATED CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Robak, T.] Med Univ Lodz, Lodz, Poland. [Jones, J.; Awan, F.] Ohio State Univ, Columbus, OH 43210 USA. [Wach, M.] Med Univ Lublin, Lublin, Poland. [Brown, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Menter, A.] Kaiser Permanente Med Grp, Denver, CO USA. [Vandenberghe, E.] St James Hosp, Dublin, Ireland. [Ysebaert, L.] Ctr Hosp Univ Purpan, Toulouse, France. [Wagner-Johnston, N.] Johns Hopkins Sch Med, Baltimore, MD USA. [Polikoff, J.] Kaiser Permanente Med Grp, San Diego, CA USA. [Badoux, X.] St George Hosp, Kogarah, NSW, Australia. [Coutre, S.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Spurgeon, S.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Loscertales, J.] Hosp Univ La Princesa, Madrid, Spain. [Xing, G.; Dubowy, R.] Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA. [Flinn, I.] Sarah Cannon Res Inst, Nashville, TN USA. [Flinn, I.; Owen, C.] Alberta Hlth Serv, Calgary, AB, Canada. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P213 BP 53 EP 53 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600116 ER PT J AU Brown, JR Ghia, P Jones, JA Pettitt, AR Sharman, JP Ysebaert, L Kim, Y Newcomb, T Yao, NS Furman, RR Stilgenbauer, S AF Brown, J. R. Ghia, P. Jones, J. A. Pettitt, A. R. Sharman, J. P. Ysebaert, L. Kim, Y. Newcomb, T. Yao, N. S. Furman, R. R. Stilgenbauer, S. TI DISCONTINUATION OF IDELALISIB TREATMENT DUE TO DISEASE PROGRESSION IN PATIENTS WITH RELAPSED AND REFRACTORY CLL: AN EVALUATION OF OUTCOMES SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Brown, J. R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ghia, P.] Univ Vita Salute San Raffaele, Milan, Italy. [Ghia, P.] IRCCS San Raffaele Sci Inst, Milan, Italy. [Jones, J. A.] Ohio State Univ, Columbus, OH 43210 USA. [Pettitt, A. R.] Univ Liverpool, Dept Mol & Clin Canc Med, Liverpool, Merseyside, England. [Sharman, J. P.] Willamette Valley Canc Inst, US Oncol Network, Springfield, OR USA. [Ysebaert, L.] Inst Univ Canc Toulouse Oncopole, Dept Haematol, Toulouse, France. [Kim, Y.; Newcomb, T.; Yao, N. S.] Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA. [Furman, R. R.] Weill Cornell Med Coll, New York, NY USA. [Stilgenbauer, S.] Univ Ulm, Ulm, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P215 BP 54 EP 54 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600118 ER PT J AU Brander, D Roberts, AW Seymour, JF Kipps, TJ Barrientos, JC Davids, MS Anderson, MA Choi, M Tam, C Prine, B Cornejo, C Zhu, M Lash, LL Ma, S AF Brander, D. Roberts, A. W. Seymour, J. F. Kipps, T. J. Barrientos, J. C. Davids, M. S. Anderson, M. A. Choi, M. Tam, C. Prine, B. Cornejo, C. Zhu, M. Lash, L. L. Ma, S. TI DURABLE TREATMENT-FREE REMISSION AND EFFECTIVE RETREATMENT IN PATIENTS WITH RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA WHO ACHIEVED A DEEP RESPONSE WITH VENETOCLAX COMBINED WITH RITUXIMAB SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Brander, D.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Roberts, A. W.; Anderson, M. A.] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Roberts, A. W.; Anderson, M. A.] Eliza Hall Inst Med Res, Canc & Hematol Div, Parkville, Vic, Australia. [Seymour, J. F.; Tam, C.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Kipps, T. J.; Choi, M.] Univ Calif San Diego, San Diego, CA 92103 USA. [Barrientos, J. C.] Hofstra Northwell Sch Med, Hempstead, NY USA. [Davids, M. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Prine, B.; Cornejo, C.; Zhu, M.; Lash, L. L.] AbbVie Inc, N Chicago, IL USA. [Ma, S.] Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 2 Z9 2 U1 2 U2 2 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P223 BP 58 EP 58 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600125 ER PT J AU Davids, MS Gerecitano, J Potluri, J Cerri, E Kim, SY Steinberg, M Verdugo, M Busman, T Enschede, SH Mobasher, M Best, A Desai, M Wierda, WG AF Davids, M. S. Gerecitano, J. Potluri, J. Cerri, E. Kim, S. Y. Steinberg, M. Verdugo, M. Busman, T. Enschede, S. Heitner Mobasher, M. Best, A. Desai, M. Wierda, W. G. TI INTEGRATED SAFETY ANALYSIS OF VENETOCLAX MONOTHERAPY IN CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Davids, M. S.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. [Gerecitano, J.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Potluri, J.; Cerri, E.; Kim, S. Y.; Steinberg, M.; Verdugo, M.; Busman, T.; Enschede, S. Heitner; Best, A.; Desai, M.] AbbVie Inc, N Chicago, IL USA. [Mobasher, M.] Genentech Inc, San Francisco, CA 94080 USA. [Wierda, W. G.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P225 BP 59 EP 59 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600127 ER PT J AU Savona, MR Odenike, O Amrein, P Steensma, D DeZern, A Michaelis, L Faderl, S Oganesian, A Lowder, J Taverna, P Azab, M Garcia-Manero, G AF Savona, M. R. Odenike, O. Amrein, P. Steensma, D. DeZern, A. Michaelis, L. Faderl, S. Oganesian, A. Lowder, J. Taverna, P. Azab, M. Garcia-Manero, G. TI PHASE 1 DOSE-ESCALATION STUDY OF ORAL ASTX727, A COMBINATION OF ORAL DECITABINE WITH A CYTIDINE DEAMINASE INHIBITOR (CDAI) E7727, IN SUBJECTS WITH MYELODYSPLASTIC SYNDROMES (MDS) SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Savona, M. R.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Odenike, O.] Univ Chicago, Chicago, IL 60637 USA. [Amrein, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Steensma, D.] Dana Farber Inst, Boston, MA USA. [DeZern, A.] Johns Hopkins Univ Hosp, Baltimore, MD USA. [Michaelis, L.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Faderl, S.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Oganesian, A.; Lowder, J.; Taverna, P.; Azab, M.] Astex Pharmaceut Inc, Pleasanton, CA USA. [Garcia-Manero, G.] UT MD Anderson Canc Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P253 BP 73 EP 73 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600156 ER PT J AU Avet-Loiseau, H Bahlis, N Chng, WJ Masszi, T Viterbo, L Pour, L Ganly, P Palumbo, A Cavo, M Langer, C Pluta, A Nagler, A Kumar, S Ben-Yehuda, D Rajkumar, SV Miguel, JS Berg, D Lin, J van de Velde, H Badola, S Gao, F Zhange, J Shen, L Li, B Esseltine, DL di Bacco, A Moreau, P Richardson, P AF Avet-Loiseau, H. Bahlis, N. Chng, W. J. Masszi, T. Viterbo, L. Pour, L. Ganly, P. Palumbo, A. Cavo, M. Langer, C. Pluta, A. Nagler, A. Kumar, S. Ben-Yehuda, D. Rajkumar, S. V. Miguel, J. San Berg, D. Lin, J. van de Velde, H. Badola, S. Gao, F. Zhange, J. Shen, L. Li, B. Esseltine, D. L. di Bacco, A. Moreau, P. Richardson, P. TI IMPACT OF CYTOGENETIC RISK STATUS ON EFFICACY AND SAFETY OF IXAZOMIB-LENALIDOMIDE-DEXAMETHASONE (IRD) VS PLACEBO-RD IN RELAPSED/REFRACTORY MULTIPLE MYELOMA PATIENTS IN THE GLOBAL TOURMALINE-MM1 STUDY SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Avet-Loiseau, H.] Univ Canc Ctr Toulouse, Inst Natl Sante, Toulouse, France. [Bahlis, N.] Univ Calgary, Southern Alberta Canc Res Inst, Calgary, AB, Canada. [Chng, W. J.] Natl Univ Canc Inst, Singapore, Singapore. [Masszi, T.] Semmelweis Univ, Dept Internal Med 3, St Laszlo Hosp, St Istvan, Budapest, Hungary. [Viterbo, L.] IPOPFG EPE, Oporto, Portugal. [Pour, L.] Univ Hosp Brno, Brno, Czech Republic. [Ganly, P.] Christchurch Hosp, Dept Haematol, Christchurch, New Zealand. [Palumbo, A.] Univ Torino, Azienda Osped Univ AOU S Giovanni Battista, Div Hematol, Myeloma Unit, Turin, Italy. [Cavo, M.] Univ Bologna, Bologna, Italy. [Langer, C.] Univ Hosp Ulm, Ulm, Germany. [Pluta, A.] Oncol Spec Hosp, Dept Hematol Oncol, Brzozow, Poland. [Nagler, A.] Chaim Sheba Med Ctr, Div Hematol, Tel Hashomer, Israel. [Kumar, S.] Mayo Clin, Rochester, NY USA. [Ben-Yehuda, D.] Kiryat Hadassah, Med Ctr, Jerusalem, Israel. [Rajkumar, S. V.] Mayo Clin, Div Hematol, Rochester, NY USA. [Miguel, J. San] Clin Univ Navarra, CIMA, Pamplona, Spain. [Berg, D.; Lin, J.; van de Velde, H.; Badola, S.; Gao, F.; Zhange, J.; Shen, L.; Li, B.; Esseltine, D. L.; di Bacco, A.] Millennium Pharmaceut Inc, Cambridge, MA USA. [Moreau, P.] Univ Hosp Hotel Dieu, Nantes, France. [Richardson, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI richard, chrystelle/K-8595-2015 NR 0 TC 1 Z9 1 U1 2 U2 3 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P269 BP 80 EP 80 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600172 ER PT J AU Dimopoulos, MA Palumbo, A Weisel, K Richardson, P Mateos, MV Moreau, P Gupta, M Sheng, J Passey, C Sy, O Katz, J Lonial, S AF Dimopoulos, M. A. Palumbo, A. Weisel, K. Richardson, P. Mateos, M. V. Moreau, P. Gupta, M. Sheng, J. Passey, C. Sy, O. Katz, J. Lonial, S. TI ELOTUZUMAB plus LENALIDOMIDE/DEXAMETHASONE IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: ELOQUENT-2 POST-HOC ANALYSIS OF PFS AND TUMOR REGROWTH BY TIME FROM DIAGNOSIS AND PRIOR LINES OF THERAPY SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Dimopoulos, M. A.] Univ Athens, Athens, Greece. [Palumbo, A.] Osped Molinette, AOU San Giovanni Battista Torino, Turin, Italy. [Weisel, K.] Univ Tubingen, Tubingen, Germany. [Richardson, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mateos, M. V.] Complejo Asistencial Univ Salamanca IBSAL, Salamanca, Spain. [Moreau, P.] Univ Hosp, Nantes, France. [Gupta, M.; Sheng, J.; Passey, C.; Sy, O.; Katz, J.] Bristol Myers Squibb, Princeton, NJ USA. [Lonial, S.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. RI richard, chrystelle/K-8595-2015 NR 1 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P280 BP 85 EP 85 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600183 ER PT J AU Palumbo, A Magarotto, V Sonneveld, P Plesner, T Paba-Prada, C Voorhees, P Mellqvist, UH Byrne, C Harmenberg, J Nordstrom, E Zubair, H Richardson, PG AF Palumbo, A. Magarotto, V. Sonneveld, P. Plesner, T. Paba-Prada, C. Voorhees, P. Mellqvist, U. H. Byrne, C. Harmenberg, J. Nordstrom, E. Zubair, H. Richardson, P. G. TI FINAL PHASE 2 STUDY DATA OF MELFLUFEN AND DEXAMETHASONE FOR PATIENTS WITH RELAPSED-REFRACTORY MULTIPLE MYELOMA (RRMM) SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Palumbo, A.; Magarotto, V.] Univ Turin, Dept Oncol, Myeloma Unit, Div Hematol, Turin, Italy. [Sonneveld, P.] Erasmus MC, Rotterdam, Netherlands. [Plesner, T.] Vejle Hosp, Hematol, Vejle, Denmark. [Paba-Prada, C.; Richardson, P. G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Voorhees, P.] Univ N Carolina, Chapel Hill, NC USA. [Mellqvist, U. H.] Sodra Alvsborgs Sjukhus, Boras, Sweden. [Byrne, C.] Oncopeptides AB, Miami, FL USA. [Harmenberg, J.; Zubair, H.] Oncopeptides AB, Stockholm, Sweden. [Nordstrom, E.] Oncopeptides AB, Clin, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P281 BP 85 EP 85 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600184 ER PT J AU Vos, J Tsakmaklis, N Meid, K Castillo, J Brodsky, P Ganz, T Xu, L Yang, G Treon, S Hunter, Z AF Vos, J. Tsakmaklis, N. Meid, K. Castillo, J. Brodsky, P. Ganz, T. Xu, L. Yang, G. Treon, S. Hunter, Z. TI BIOLOGICALLY MEANINGFUL CHANGES IN CYTOKINE AND CHEMOKINE PRODUCTION FOLLOWING IBRUTINIB THERAPY IN WALDENSTROM'S MACROGLOBULINEMIA SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Vos, J.] Sint Antonius Ziekenhuis, Int Med Hematol, Nieuwegein, Netherlands. [Vos, J.] Dana Farber Canc Insitute, Bing Ctr WM, Boston, MA USA. [Tsakmaklis, N.; Meid, K.; Castillo, J.; Brodsky, P.; Xu, L.; Yang, G.; Treon, S.; Hunter, Z.] Dana Farber Canc Inst, Bing Ctr WM, Boston, MA 02115 USA. [Ganz, T.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P312 BP 101 EP 102 PG 2 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600218 ER PT J AU Casulo, C Jacobsen, E Van Eygen, K Holmes, HE Lemmens, JP Allen, K Steelman, L Campbell, V Nevejans, J Pearlberg, J Goy, A AF Casulo, C. Jacobsen, E. Van Eygen, K. Holmes, H. E. Lemmens, J. P. Allen, K. Steelman, L. Campbell, V. Nevejans, J. Pearlberg, J. Goy, A. TI PRELIMINARY SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF DUVELISIB PLUS RITUXIMAB OR OBINUTUZUMAB IN PATIENTS WITH PREVIOUSLY UNTREATED CD20+FOLLICULAR LYMPHOMA SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Casulo, C.] Univ Rochester, Strong Mem Hosp, James P Wilmont Canc Ctr, Rochester, NY 14642 USA. [Jacobsen, E.] Dana Farber Canc Inst, Partners Canc Care, Boston, MA 02115 USA. [Van Eygen, K.] AZ Groeninge, Kortrijk, Belgium. [Holmes, H. E.] Texas Oncol PA, Dallas, TX USA. [Lemmens, J. P.] Med Inst St Augustinus, Antwerp, Belgium. [Allen, K.; Steelman, L.; Campbell, V.; Nevejans, J.; Pearlberg, J.] Infin Pharmaceut Inc, Cambridge, MA USA. [Goy, A.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P319 BP 104 EP 104 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600225 ER PT J AU Herrera, AF Low, L Griffin, G Mei, M Merryman, R Song, J Bedell, V Sun, H Paris, T Stiller, T Alyea, E Brown, J Budde, E Chen, R Chen, YB Chan, WC Cutler, C Davids, M Freeman, A Fisher, D Ho, V Jacobsen, E Jacobson, C Koreth, J LaCasce, A Murata-Collins, J Murata-Collins, J Nademanee, A Nikiforow, S Palmer, J Pihan, G Pillai, R Siddiqi, T Sohani, A Popplewell, L Zain, J Kwak, L Weinstock, D Soiffer, R Antin, J Forman, S Weisenburger, D Rodig, S Kim, Y Krishnan, A Armand, P AF Herrera, A. F. Low, L. Griffin, G. Mei, M. Merryman, R. Song, J. Bedell, V. Sun, H. Paris, T. Stiller, T. Alyea, E. Brown, J. Budde, E. Chen, R. Chen, Y. B. Chan, W. C. Cutler, C. Davids, M. Freeman, A. Fisher, D. Ho, V. Jacobsen, E. Jacobson, C. Koreth, J. LaCasce, A. Murata-Collins, J. Murata-Collins, J. Nademanee, A. Nikiforow, S. Palmer, J. Pihan, G. Pillai, R. Siddiqi, T. Sohani, A. Popplewell, L. Zain, J. Kwak, L. Weinstock, D. Soiffer, R. Antin, J. Forman, S. Weisenburger, D. Rodig, S. Kim, Y. Krishnan, A. Armand, P. TI OUTCOMES AFTER AUTOLOGOUS AND ALLOGENEIC STEM CELL TRANSPLANTATION (SCT) IN DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) PATIENTS WITH MYC/BCL2 CO-EXPRESSION, DOUBLE-HIT LYMPHOMA, OR MYC COPY GAIN SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Herrera, A. F.; Mei, M.; Budde, E.; Chen, R.; Nademanee, A.; Siddiqi, T.; Popplewell, L.; Zain, J.; Kwak, L.; Forman, S.; Krishnan, A.] City Hope Natl Med Ctr, Hematol HCT, Duarte, CA USA. [Low, L.; Song, J.; Bedell, V.; Chan, W. C.; Murata-Collins, J.; Murata-Collins, J.; Pillai, R.; Weisenburger, D.; Kim, Y.] City Hope Natl Med Ctr, Pathol, Duarte, CA USA. [Griffin, G.; Sun, H.; Rodig, S.] Brigham & Womens Hosp, Pathol, 75 Francis St, Boston, MA 02115 USA. [Merryman, R.] Brigham & Womens Hosp, Med, 75 Francis St, Boston, MA 02115 USA. [Paris, T.; Stiller, T.; Palmer, J.] City Hope Natl Med Ctr, Informat Sci, Duarte, CA USA. [Alyea, E.; Brown, J.; Cutler, C.; Davids, M.; Freeman, A.; Fisher, D.; Ho, V.; Jacobsen, E.; Jacobson, C.; Koreth, J.; LaCasce, A.; Nikiforow, S.; Weisenburger, D.; Rodig, S.; Kim, Y.; Armand, P.] Dana Farber Canc Inst, Hematol Malignancies, Boston, MA 02115 USA. [Chen, Y. B.] Massachusetts Gen Hosp, Bone Marrow Transplantat, Boston, MA 02114 USA. [Pihan, G.] Beth Israel Deaconess Med Ctr, Pathol, Boston, MA 02215 USA. [Sohani, A.] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P340 BP 113 EP 114 PG 2 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600246 ER PT J AU Wierda, W Jones, J Furman, R Stephens, D Devereux, S Brown, J Hillmen, P Hamdy, A Fardis, M Tawashi, M Wang, MH Patel, P Mittag, D Krantz, F Rothbaum, W Izumi, R O'Brien, S Byrd, J AF Wierda, W. Jones, J. Furman, R. Stephens, D. Devereux, S. Brown, J. Hillmen, P. Hamdy, A. Fardis, M. Tawashi, M. Wang, M. H. Patel, P. Mittag, D. Krantz, F. Rothbaum, W. Izumi, R. O'Brien, S. Byrd, J. TI ACALABRUTINIB, A SECOND-GENERATION BRUTON TYROSINE KINASE (BTK) INHIBITOR, IN PREVIOUSLY UNTREATED CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Wierda, W.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Jones, J.; Byrd, J.] Ohio State Univ, Columbus, OH 43210 USA. [Furman, R.] Weill Cornell Med Coll, New York, NY USA. [Stephens, D.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Devereux, S.] Coll Hosp, London, England. [Brown, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hillmen, P.] St James Univ Hosp, Leeds, W Yorkshire, England. [Hamdy, A.; Fardis, M.; Tawashi, M.; Wang, M. H.; Patel, P.; Krantz, F.; Rothbaum, W.; Izumi, R.] Acerta Pharma, Redwood City, CA USA. [Mittag, D.] Acerta Pharma, Oss, Netherlands. [O'Brien, S.] Univ Calif Irvine, Irvine, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA S431 BP 151 EP 151 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600337 ER PT J AU Bolli, N Biancon, G Gimondi, S Li, Y Vijitha, S Maura, F Carniti, C Fulciniti, M Szalat, R Anderson, KC Minvielle, S Attal, M Moreau, P Campbell, PC Avet-Loiseau, H Munshi, NC AF Bolli, N. Biancon, G. Gimondi, S. Li, Y. Vijitha, S. Maura, F. Carniti, C. Fulciniti, M. Szalat, R. Anderson, K. C. Minvielle, S. Attal, M. Moreau, P. Campbell, P. C. Avet-Loiseau, H. Munshi, N. C. TI A TARGETED SEQUENCING APPROACH IN MULTIPLE MYELOMA REVEALS A COMPLEX LANDSCAPE OF GENOMIC LESIONS THAT HAS IMPLICATIONS FOR PROGNOSIS SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Bolli, N.; Biancon, G.; Gimondi, S.; Maura, F.] Univ Milan, Milan, Italy. [Li, Y.; Vijitha, S.; Campbell, P. C.] Wellcome Trust Sanger Inst, Cambridge, England. [Carniti, C.] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Fulciniti, M.; Szalat, R.; Anderson, K. C.; Munshi, N. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Minvielle, S.] Univ Nantes, Nantes, France. [Attal, M.; Avet-Loiseau, H.] Inst Univ Canc Toulouse, Toulouse, France. [Moreau, P.] CHU Nantes, Nantes, France. RI richard, chrystelle/K-8595-2015 NR 0 TC 0 Z9 0 U1 1 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA S447 BP 160 EP 160 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600353 ER PT J AU Johnsen, HE Bodker, JS Schmitz, A Falgreen, S Perez-Andres, M Samur, MK Davies, F Pawlyn, C Kaiser, M Johnson, D Bertsch, U Broijl, A van Duin, M Shah, R Kjeldsen, MK Bergkvist, KS Bilgrau, AE Johansen, P El-Galaly, TC Samworth, R Sonneveld, P Goldschmidt, H Morgan, GJ Orfao, A Munshi, N Dybkr, K Bogsted, M AF Johnsen, H. E. Bodker, J. S. Schmitz, A. Falgreen, S. Perez-Andres, M. Samur, M. K. Davies, F. Pawlyn, C. Kaiser, M. Johnson, D. Bertsch, U. Broijl, A. van Duin, M. Shah, R. Kjeldsen, M. K. Bergkvist, K. S. Bilgrau, A. E. Johansen, P. El-Galaly, T. C. Samworth, R. Sonneveld, P. Goldschmidt, H. Morgan, G. J. Orfao, A. Munshi, N. Dybkr, K. Bogsted, M. TI A NEW MULTIPLE MYELOMA CLASSIFICATION SYSTEM THAT CORRELATES TO DISEASE STAGE AND PROGNOSIS - INDICATION OF REVERSIBLE PHENOTYPIC PLASTICITY AS A HALLMARK SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Johnsen, H. E.; Bodker, J. S.; Schmitz, A.; Falgreen, S.; Perez-Andres, M.; Kjeldsen, M. K.; Bergkvist, K. S.; Bilgrau, A. E.; El-Galaly, T. C.; Dybkr, K.; Bogsted, M.] Aalborg Univ Hosp, Dept Haematol, Aalborg, Denmark. [Johnsen, H. E.; El-Galaly, T. C.; Dybkr, K.; Bogsted, M.] Aalborg Univ Hosp, Clin Canc Res Ctr, Aalborg, Denmark. [Johnsen, H. E.; El-Galaly, T. C.; Dybkr, K.; Bogsted, M.] Aalborg Univ, Dept Clin Med, Aalborg, Denmark. [Perez-Andres, M.; Orfao, A.] Univ Salamanca USAL, Dept Med, Canc Res Ctr IBM CC CSIC USAL, Salamanca, Spain. [Perez-Andres, M.; Orfao, A.] Univ Salamanca USAL, Cytometry Serv NUCLEUS, Salamanca, Spain. [Perez-Andres, M.; Orfao, A.] IBSAL, Salamanca, Spain. [Samur, M. K.; Munshi, N.] Harvard Med Sch, LeBow Inst Myeloma Therapeut, Boston, MA 02215 USA. [Samur, M. K.; Munshi, N.] Harvard Med Sch, Jerome Lipper Myeloma Ctr, Dana Farber Canc Inst, Boston, MA 02215 USA. [Davies, F.; Pawlyn, C.; Kaiser, M.; Johnson, D.; Morgan, G. J.] Inst Canc Res, London, England. [Davies, F.; Morgan, G. J.] Univ Arkansas Med Sci, Myeloma Inst, Little Rock, AR 72205 USA. [Bertsch, U.; Goldschmidt, H.] Heidelberg Univ, Dept Internal Med 5, Heidelberg, Germany. [Bertsch, U.; Goldschmidt, H.] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany. [Broijl, A.; van Duin, M.; Sonneveld, P.] Erasmus MC, Dept Hematol, Rotterdam, Netherlands. [Shah, R.; Samworth, R.] Univ Cambridge, Ctr Math Sci, Cambridge, England. [Johansen, P.] Aalborg Univ Hosp, Dept Haematopathol, Aalborg, Denmark. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA S448 BP 160 EP 160 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600354 ER PT J AU Manier, S Huynh, D Salem, K Ebright, R Park, J Glavey, S Shi, J Sacco, A Roccaro, A Snyder, J Brown, L Facon, T Whitesell, L Porco, J Ghobrial, I AF Manier, S. Huynh, D. Salem, K. Ebright, R. Park, J. Glavey, S. Shi, J. Sacco, A. Roccaro, A. Snyder, J. Brown, L. Facon, T. Whitesell, L. Porco, J. Ghobrial, I. TI DEFINING NEW THERAPEUTIC AGENTS THAT TARGET THE ONCOGENIC TRANSLATION PROGRAM IN MULTIPLE MYELOMA SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Manier, S.; Facon, T.] Lille Hosp, Dept Hematol, Lille, France. [Manier, S.] Univ Lille 2, INSERM U1172, Lille, France. [Manier, S.; Huynh, D.; Salem, K.; Ebright, R.; Park, J.; Glavey, S.; Shi, J.; Sacco, A.; Roccaro, A.; Ghobrial, I.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Snyder, J.; Brown, L.; Porco, J.] Boston Univ, Ctr Mol Discovery, Boston, MA 02215 USA. [Whitesell, L.] Whitehead Inst, Cambridge, MA 02142 USA. RI FACON, THIERRY/M-9736-2014 OI FACON, THIERRY/0000-0001-7705-8460 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA S449 BP 161 EP 161 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600355 ER PT J AU DeAngelo, DJ Jabbour, EJ Stelljes, M Liedtke, M Stock, W Goekbuget, N Martinelli, G O'Brien, S Wang, K Wang, T Paccagnella, ML Sleight, B Vandendries, E Advani, AS Kantarjian, HM AF DeAngelo, D. J. Jabbour, E. J. Stelljes, M. Liedtke, M. Stock, W. Goekbuget, N. Martinelli, G. O'Brien, S. Wang, K. Wang, T. Paccagnella, M. L. Sleight, B. Vandendries, E. Advani, A. S. Kantarjian, H. M. TI INOTUZUMAB OZOGAMICIN FOR RELAPSED/REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA IN THE GLOBAL PHASE 3 RANDOMIZED CONTROLLED INO-VATE TRIAL: EFFICACY AND SAFETY BY PRIOR THERAPY SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [DeAngelo, D. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jabbour, E. J.; Kantarjian, H. M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Stelljes, M.] Univ Klinikum mUNSTER, Munster, Germany. [Liedtke, M.] Stanford Canc Ctr, Stanford, CA USA. [Stock, W.] Univ Chicago Med, Chicago, IL USA. [Goekbuget, N.] Univ Hosp Frankfurt, Frankfurt, Germany. [Martinelli, G.] Univ Bologna, Bologna, Italy. [O'Brien, S.] Univ Calif Irvine, Orange, CA 92668 USA. [Wang, K.] Pfizer Inc, Pearl River, NY USA. [Wang, T.; Paccagnella, M. L.; Sleight, B.] Pfizer Inc, Groton, CT 06340 USA. [Vandendries, E.] Pfizer Inc, Cambridge, MA USA. [Advani, A. S.] Cleveland Clin Main Campus, Cleveland, OH USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA S499 BP 184 EP 184 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600405 ER PT J AU Dohner, H Symeonidis, A Sanz, MA Deeren, D Demeter, J Anagnostopoulos, A Esteve, J Fiedler, W Porkka, K Kim, HJ Lee, JH Usuki, K Jung, CW D'Ardia, S Salamero, O Horst, HA Recher, C Rousselot, P Sandhu, I Theunissen, K Thol, F Dohner, K Teleanu, V DeAngelo, DJ Naoe, T Sekeres, MA Belsack, V Ge, M Taube, T Ottmann, OG AF Dohner, H. Symeonidis, A. Sanz, M. A. Deeren, D. Demeter, J. Anagnostopoulos, A. Esteve, J. Fiedler, W. Porkka, K. Kim, H. J. Lee, J. H. Usuki, K. Jung, C. W. D'Ardia, S. Salamero, O. Horst, H. A. Recher, C. Rousselot, P. Sandhu, I. Theunissen, K. Thol, F. Dohner, K. Teleanu, V. DeAngelo, D. J. Naoe, T. Sekeres, M. A. Belsack, V. Ge, M. Taube, T. Ottmann, O. G. TI PHASE III RANDOMIZED TRIAL OF VOLASERTIB PLUS LOW-DOSE CYTARABINE (LDAC) VERSUS PLACEBO PLUS LDAC IN PATIENTS AGED >= 65 YEARS WITH PREVIOUSLY UNTREATED AML, INELIGIBLE FOR INTENSIVE THERAPY SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Dohner, H.; Dohner, K.; Teleanu, V.] Univ Ulm, Ulm, Germany. [Symeonidis, A.] Univ Hosp Patras, Patras, Greece. [Sanz, M. A.] Univ Hosp La Fe, Valencia, Spain. [Deeren, D.] H Hartziekenhuis Roeselare Menen, Roselare, Belgium. [Demeter, J.] Semmelweis Univ, Budapest, Hungary. [Anagnostopoulos, A.] Gen Hosp G Papanikolaou, Thessaloniki, Greece. [Esteve, J.] Hosp Clin Barcelona, Barcelona, Spain. [Fiedler, W.] Univ Klinikum Hamburg Eppendorf, Hamburg, Germany. [Porkka, K.] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Kim, H. J.] Catholic Univ Korea, Seoul St Marys Hosp, Seoul, South Korea. [Lee, J. H.] Asan Med Ctr, Seoul, South Korea. [Usuki, K.] NTT Med Ctr Tokyo, Tokyo, Japan. [Jung, C. W.] Samsung Med Ctr, Seoul, South Korea. [D'Ardia, S.] AO Citta Salute & Sci, Turin, Italy. [Salamero, O.] Hosp Vall d Hebron, Barcelona, Spain. [Horst, H. A.] UKSH Campus Kiel, Kiel, Germany. [Recher, C.] Univ Toulouse 3, IUCT Oncopole, Ctr Hosp Univ Toulouse, Toulouse, France. [Rousselot, P.] Ctr Hosp Andre Mignot, Le Chesnay, France. [Sandhu, I.] Univ Alberta Hosp, Edmonton, AB, Canada. [Theunissen, K.] Jessa Ziekenhuis, Hasselt, Belgium. [Thol, F.] Hannover Med Sch, Hannover, Germany. [DeAngelo, D. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Naoe, T.] Nagoya Med Ctr, Natl Hosp Org, Nagoya, Aichi, Japan. [Sekeres, M. A.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Belsack, V.] SCS Boehringer Ingelheim Comm V, Brussels, Belgium. [Ge, M.] Boehringer Ingelheim Corp, Ridgefield, CT USA. [Taube, T.] Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany. [Ottmann, O. G.] Goethe Univ Frankfurt, Frankfurt, Germany. RI Porkka, Kimmo/O-2323-2016 OI Porkka, Kimmo/0000-0003-4112-5902 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA S501 BP 185 EP 186 PG 2 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600407 ER PT J AU Fathi, A Erba, H Lancet, J Stein, E Ravandi, F Faderl, S Walter, R Advani, A DeAngelo, D Kovacsovics, T Jillella, A Bixby, D Levy, M O'Meara, M Ho, P Stein, A AF Fathi, A. Erba, H. Lancet, J. Stein, E. Ravandi, F. Faderl, S. Walter, R. Advani, A. DeAngelo, D. Kovacsovics, T. Jillella, A. Bixby, D. Levy, M. O'Meara, M. Ho, P. Stein, A. TI SGN-CD33A IN COMBINATION WITH HYPOMETHYLATING AGENTS: A NOVEL, WELL-TOLERATED REGIMEN WITH HIGH REMISSION RATE IN OLDER PATIENTS WITH AML SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Fathi, A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Erba, H.] Univ Alabama Birmingham, Burmingham, AL USA. [Lancet, J.] Moffitt Ctr, Tampa, FL USA. [Stein, E.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Ravandi, F.] MD Anderson Univ Texas Houston, Houston, TX USA. [Faderl, S.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Walter, R.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Advani, A.] Cleveland Clin, Cleveland, OH 44106 USA. [DeAngelo, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kovacsovics, T.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Jillella, A.] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA. [Bixby, D.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Levy, M.] Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. [O'Meara, M.; Ho, P.] Seattle Genet Inc, Bothell, WA USA. [Stein, A.] City Hope Natl Med Ctr, Gehr Family Ctr Leukemia Res, Duarte, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA S503 BP 186 EP 187 PG 2 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600409 ER PT J AU Lancet, J Uy, G Cortes, J Newell, L Lin, T Ritchie, E Strickland, S Stuart, R Hogge, D Solomon, S Stone, R Bixby, D Kolitz, J Schiller, G Wieduwilt, M Rao, A Rubenstein, S Stock, W Foster, M Erba, H Goldberg, S Powell, B Podoltsev, N Atallah, E Warlick, E Yee, K Pagel, J Norkin, M Barta, S Sandhu, I Frankfurt, O Gautier, M Larson, M Seiter, K Levy, M Bergeron, J Berdeja, J Kropf, P Shemanski, L Ryan, D Chiarella, M Paulsen, K Louie, A Medeiros, B AF Lancet, J. Uy, G. Cortes, J. Newell, L. Lin, T. Ritchie, E. Strickland, S. Stuart, R. Hogge, D. Solomon, S. Stone, R. Bixby, D. Kolitz, J. Schiller, G. Wieduwilt, M. Rao, A. Rubenstein, S. Stock, W. Foster, M. Erba, H. Goldberg, S. Powell, B. Podoltsev, N. Atallah, E. Warlick, E. Yee, K. Pagel, J. Norkin, M. Barta, S. Sandhu, I. Frankfurt, O. Gautier, M. Larson, M. Seiter, K. Levy, M. Bergeron, J. Berdeja, J. Kropf, P. Shemanski, L. Ryan, D. Chiarella, M. Paulsen, K. Louie, A. Medeiros, B. TI CPX-351 TREATMENT OF PREVIOUSLY UNTREATED OLDER AML PATIENTS WITH HIGH RISK AML MARKEDLY INCREASES THE RESPONSE RATE OVER 7+3 IN PATIENTS WITH FLT3 MUTATIONS SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Lancet, J.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Uy, G.] Washington Univ, Sch Med, St Louis, MO USA. [Cortes, J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Newell, L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Lin, T.] Univ Kansas, Ctr Canc, Westwood, KS USA. [Ritchie, E.] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA. [Strickland, S.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Stuart, R.] Med Univ S Carolina, Charleston, SC USA. [Hogge, D.] BC Canc Res Ctr, Vancouver, BC, Canada. [Solomon, S.] Northside Hosp, Blood & Marrow Transplant Grp, Atlanta, GA USA. [Stone, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bixby, D.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Kolitz, J.] N Shore Univ Hosp, LIJ Hlth Syst, Lake Success, NY USA. [Schiller, G.] UCLA Med Ctr, Los Angeles, CA USA. [Wieduwilt, M.] Moores UC San Diego Canc Ctr, La Jolla, CA USA. [Rao, A.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Rubenstein, S.] Franciscan St Francis Hlth, Indianapolis, IN USA. [Stock, W.] Univ Chicago, Chicago, IL 60637 USA. [Foster, M.] Univ N Carolina, Chapel Hill, NC USA. [Erba, H.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Goldberg, S.] Hackensack Univ, Med Ctr, John Theuer Canc Ctr, Hackensack, NJ USA. [Powell, B.] Wake Forest Baptist Hlth, Winston Salem, NC USA. [Podoltsev, N.] Yale Univ, Sch Med, New Haven, CT USA. [Atallah, E.] Froedtert, Milwaukee, WI USA. [Atallah, E.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Warlick, E.] Univ Minnesota, Minneapolis, MN USA. [Yee, K.] Princess Margaret Hosp, Toronto, ON, Canada. [Pagel, J.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Norkin, M.] Univ Florida, Coll Med, Gainesville, FL USA. [Barta, S.] Montefiore Med Ctr, 111 E 210th St, Bronx, NY 10467 USA. [Sandhu, I.] Univ Alberta Hosp, Edmonton, AB, Canada. [Frankfurt, O.] Northwestern Univ, Chicago, IL 60611 USA. [Gautier, M.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Larson, M.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Seiter, K.] New York Med Coll, Hawthorne, NY USA. [Levy, M.] Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. [Bergeron, J.] Univ Montreal, Hop Maison Neuve Rosemont, Montreal, PQ, Canada. [Berdeja, J.] Sarah Cannon Res Inst, Nashville, TN USA. [Kropf, P.] Jeanes Hosp, Temple BMT Program, Philadelphia, PA USA. [Shemanski, L.] Canc Res & Biostat, Seattle, WA USA. [Ryan, D.] Univ Rochester, Rochester, NY 14627 USA. [Chiarella, M.; Paulsen, K.; Louie, A.] Celator Pharmaceut, Ewing, NJ USA. [Medeiros, B.] Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA S502 BP 186 EP 186 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600408 ER PT J AU Seymour, JF Dohner, H Schuh, AC Stone, RM Minden, M Weaver, J Songer, S Beach, C Dombret, H AF Seymour, J. F. Doehner, H. Schuh, A. C. Stone, R. M. Minden, M. Weaver, J. Songer, S. Beach, C. Dombret, H. TI AZACITIDINE (AZA) VS CONVENTIONAL CARE REGIMENS (CCR) IN PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML) WITH MYELODYSPLASIA-RELATED CHANGES (MRC) IN AZA-AML-001 PER CENTRAL REVIEW SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Seymour, J. F.] Peter MacCallum Canc Ctr, East Melbourne, Vic, Australia. [Doehner, H.] Univ Ulm Klinikum, Ulm, Germany. [Schuh, A. C.; Minden, M.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Stone, R. M.] Dana Farber Canc Inst, Boston, MA USA. [Weaver, J.; Songer, S.; Beach, C.] Celgene Corp, Summit, NJ USA. [Dombret, H.] Hop St Louis, Inst Univ Hematol, Paris, France. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P573 BP 218 EP 219 PG 2 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600479 ER PT J AU Seymour, JF Dohner, H Stone, RM Gambini, D Dougherty, D Weaver, J Beach, C Dombret, H AF Seymour, J. F. Doehner, H. Stone, R. M. Gambini, D. Dougherty, D. Weaver, J. Beach, C. Dombret, H. TI HOSPITALIZATION FOR TREATMENT-EMERGENT ADVERSE EVENTS (TEAE) IN OLDER (>= 65 YEARS) PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML) WITH > 30% MARROW BLASTS IN THE PHASE 3 AZA-AML-001 STUDY SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Seymour, J. F.] Peter MacCallum Canc Ctr, East Melbourne, Australia. [Doehner, H.] Univ Ulm Klinikum, Ulm, Germany. [Stone, R. M.] Dana Farber Canc Inst, Boston, MA USA. [Gambini, D.; Dougherty, D.; Weaver, J.; Beach, C.] Celgene Corp, Summit, NJ USA. [Dombret, H.] Univ Paris Diderot, Hop St Louis, Inst Univ Hematol, Paris, France. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P576 BP 219 EP 220 PG 2 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600482 ER PT J AU Sorror, M Storer, B Elsawy, M Fathi, A Brunner, A Gerds, A Sekeres, M Mukherjee, S Medeiros, B Shami, P Pena, E Wardyn, S Whitten, J Becker, P McCune, J Lee, S Sandmaier, B Appelbaum, F Estey, E AF Sorror, M. Storer, B. Elsawy, M. Fathi, A. Brunner, A. Gerds, A. Sekeres, M. Mukherjee, S. Medeiros, B. Shami, P. Pena, E. Wardyn, S. Whitten, J. Becker, P. McCune, J. Lee, S. Sandmaier, B. Appelbaum, F. Estey, E. TI RELATIVE BENEFIT FOR INTENSIVE VERSUS NON-INTENSIVE INDUCTION THERAPY FOR PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA (AML) USING A COMPOSITE, AGE-COMORBIDITY-CYTOGENETIC, MODEL SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Sorror, M.; Storer, B.; Elsawy, M.; Wardyn, S.; Whitten, J.; McCune, J.; Lee, S.; Sandmaier, B.; Appelbaum, F.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Sorror, M.; Storer, B.; Becker, P.; McCune, J.; Lee, S.; Sandmaier, B.; Appelbaum, F.; Estey, E.] Univ Washington, Seattle, WA 98195 USA. [Fathi, A.; Brunner, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gerds, A.; Sekeres, M.; Mukherjee, S.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Medeiros, B.] Stanford Univ, Palo Alto, CA 94304 USA. [Shami, P.; Pena, E.] Univ Utah, Salt Lake City, UT USA. [Becker, P.; Estey, E.] Seattle Canc Care Alliance, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA LB580 BP 221 EP 222 PG 2 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600486 ER PT J AU Anderson, MA Roberts, AW Seymour, JF Gerecitano, JF Kahl, BS Kipps, TJ Pagel, JM Puvvada, SD Wierda, WG Gressick, L Zhu, M Dunbar, M Chyla, B Verdugo, M Kim, SY Davids, MS AF Anderson, M. A. Roberts, A. W. Seymour, J. F. Gerecitano, J. F. Kahl, B. S. Kipps, T. J. Pagel, J. M. Puvvada, S. D. Wierda, W. G. Gressick, L. Zhu, M. Dunbar, M. Chyla, B. Verdugo, M. Kim, S. Y. Davids, M. S. TI SAFETY, EFFICACY AND IMMUNE EFFECTS OF VENETOCLAX 400 MG DAILY IN PATIENTS (PTS) WITH RELAPSED CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Anderson, M. A.; Roberts, A. W.] Royal Melbourne Hosp, Dept Clin Haematol & BMT, Parkville, Vic, Australia. [Anderson, M. A.; Roberts, A. W.] Walter & Eliza Hall Inst Med Res, Div Canc & Haematol, Parkville, Vic, Australia. [Anderson, M. A.; Roberts, A. W.; Seymour, J. F.] Univ Melbourne, Victorian Comprehens Canc Ctr, Parkville, Vic, Australia. [Anderson, M. A.; Roberts, A. W.; Seymour, J. F.] Univ Melbourne, Fac Med, Parkville, Vic, Australia. [Gerecitano, J. F.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Gerecitano, J. F.] Weill Cornell Med Coll, New York, NY USA. [Kahl, B. S.] Washington Univ, St Louis, MO USA. [Kipps, T. J.] Univ Calif San Diego, San Diego, CA 92103 USA. [Pagel, J. M.] Swedish Med Ctr, Seattle, WA USA. [Puvvada, S. D.] Univ Arizona, Tucson, AZ USA. [Wierda, W. G.] Univ Texas Austin, Austin, TX 78712 USA. [Gressick, L.; Zhu, M.; Dunbar, M.; Chyla, B.; Verdugo, M.; Kim, S. Y.] AbbVie Inc, N Chicago, IL USA. [Davids, M. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P591 BP 228 EP 228 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600499 ER PT J AU Hillmen, P O'Brien, SM Byrd, JC Coutre, S Brown, JR Barr, PM Barrientos, JC Devereux, S Robak, T Reddy, NM Kipps, TJ Tedeschi, A Cymbalista, F Ghia, P Chang, S Ninomoto, J James, DF Burger, JA AF Hillmen, P. O'Brien, S. M. Byrd, J. C. Coutre, S. Brown, J. R. Barr, P. M. Barrientos, J. C. Devereux, S. Robak, T. Reddy, N. M. Kipps, T. J. Tedeschi, A. Cymbalista, F. Ghia, P. Chang, S. Ninomoto, J. James, D. F. Burger, J. A. TI OUTCOMES WITH SINGLE-AGENT IBRUTINIB BY PRIOR LINE OF THERAPY AND FOLLOWING IBRUTINIB DISCONTINUATION IN PATIENTS WITH CLL: ANALYSES FROM PHASE 3 STUDIES SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Hillmen, P.] St James Inst Oncol, Leeds Teaching Hosp, Leeds, W Yorkshire, England. [O'Brien, S. M.] Univ Calif Irvine, Irvine, CA USA. [Byrd, J. C.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Coutre, S.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Brown, J. R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Barr, P. M.] Univ Rochester, Wilmot Canc Inst, Rochester, NY USA. [Barrientos, J. C.] Hofstra Northwell Sch Med, Hempstead, NY USA. [Devereux, S.] Kings Coll Hosp London, London, England. [Robak, T.] Med Univ Lodz, Lodz, Poland. [Robak, T.] Copernicus Mem Hosp, Lodz, Poland. [Reddy, N. M.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Kipps, T. J.] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA. [Tedeschi, A.] Azienda Osped Niguarda Ca Granda, Milan, Italy. [Cymbalista, F.] Hop Avicenne, Paris, France. [Ghia, P.] Univ Vita Salute San Raffaele, Milan, Italy. [Ghia, P.] IRCCS Ist Sci San Raffaele, Milan, Italy. [Chang, S.; Ninomoto, J.; James, D. F.] Pharmacyclics LLC, Sunnyvale, CA USA. [Burger, J. A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P596 BP 230 EP 230 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600504 ER PT J AU Coutre, S Wierda, W Choi, M Davids, MS Cheson, BD Furman, RR Lamanna, N Barr, PM Eradat, H Halwani, A Heffner, L Chyla, B Zhu, M Potluri, J Verdugo, M Humerickhouse, R Mato, AR Jones, J AF Coutre, S. Wierda, W. Choi, M. Davids, M. S. Cheson, B. D. Furman, R. R. Lamanna, N. Barr, P. M. Eradat, H. Halwani, A. Heffner, L. Chyla, B. Zhu, M. Potluri, J. Verdugo, M. Humerickhouse, R. Mato, A. R. Jones, J. TI VENETOCLAX IS ACTIVE IN CLL PATIENTS WHO HAVE RELAPSED AFTER OR ARE REFRACTORY TO IBRUTINIB OR IDELALISIB SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Coutre, S.] Stanford Univ, Sch Med, Stanford Canc Ctr, Stanford, CA 94305 USA. [Wierda, W.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Choi, M.] UCSD Moores Canc Ctr, San Diego, CA USA. [Davids, M. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cheson, B. D.] Georgetown Univ Hosp, Washington, DC 20007 USA. [Furman, R. R.] Weill Cornell Med, New York, NY USA. [Lamanna, N.] Columbia Univ, Med Ctr, New York, NY USA. [Barr, P. M.] Univ Rochester, Med Ctr, Wilmot Canc Inst, Rochester, NY 14642 USA. [Eradat, H.] Univ Calif Los Angeles, Los Angeles, CA USA. [Halwani, A.] Univ Utah Healthcare, Salt Lake City, UT USA. [Heffner, L.] Emory Univ, Sch Med, Atlanta, GA USA. [Chyla, B.; Zhu, M.; Potluri, J.; Verdugo, M.; Humerickhouse, R.] AbbVie Inc, N Chicago, IL USA. [Mato, A. R.] Univ Penn, Ctr CLL, Philadelphia, PA 19104 USA. [Jones, J.] Ohio State Univ, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P599 BP 231 EP 232 PG 2 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484600507 ER PT J AU Madan, S Atanackovic, D Supko, J Tamang, D Jones, SS Wheeler, C Trede, NS Anderson, L AF Madan, S. Atanackovic, D. Supko, J. Tamang, D. Jones, S. S. Wheeler, C. Trede, N. S. Anderson, L. TI PHASE 1B STUDY OF AN ALTERNATIVE LIQUID FORMULATION OF ACY-1215 (RICOLINOSTAT) IN COMBINATION WITH POMALIDOMIDE AND DEXAMETHASONE IN PATIENTS WITH RELAPSED OR RELAPSEDAND- REFRACTORY MULTIPLE MYELOMA SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Madan, S.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Atanackovic, D.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Supko, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tamang, D.; Jones, S. S.; Wheeler, C.; Trede, N. S.] Acetylon Pharmaceut Inc, Boston, MA USA. [Anderson, L.] Univ Texas Southwestern Med Ctr, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P648 BP 254 EP 254 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484601009 ER PT J AU Dimopoulos, M Trotman, J Tedeschi, A Matous, JV Macdonald, D Tam, C Tournilhac, O Ma, S Oriol, A Heffner, L Shustik, C Garcia-Sanz, R Cornell, RF de Larrea, CF Castillo, JJ Granell, M Kyrtsonis, MC Leblond, V Symeonidis, A Singh, P Li, J Graef, T Bilotti, E Treon, S Buske, C AF Dimopoulos, M. Trotman, J. Tedeschi, A. Matous, J. V. Macdonald, D. Tam, C. Tournilhac, O. Ma, S. Oriol, A. Heffner, L. Shustik, C. Garcia-Sanz, R. Cornell, R. F. Fernandez de Larrea, C. Castillo, J. J. Granell, M. Kyrtsonis, M. C. Leblond, V. Symeonidis, A. Singh, P. Li, J. Graef, T. Bilotti, E. Treon, S. Buske, C. TI SINGLE-AGENT IBRUTINIB IN RITUXIMAB-REFRACTORY PATIENTS WITH WALDENSTROM'S MACROGLOBULINEMIA (WM): UPDATED RESULTS FROM A MULTICENTER, OPEN-LABEL PHASE 3 SUBSTUDY (INNOVATETM) SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Dimopoulos, M.] Univ Athens, Sch Med, Athens 11528, Greece. [Trotman, J.] Univ Sydney, Concord Hosp, Sydney, NSW 2006, Australia. [Tedeschi, A.] Osped Niguarda Ca Granda, Milan, Italy. [Matous, J. V.] Colorado Blood Canc Inst, Denver, CO USA. [Macdonald, D.] Dalhousie Univ, Halifax, NS, Canada. [Tam, C.] Peter MacCallum Canc Ctr, Melbourne, Australia. [Tam, C.] St Vincents Hosp, Melbourne, Australia. [Tournilhac, O.] CHU Clermont Ferrand, Hematol Clin Adulte & Therapie Cellulaire, Clermont Ferrand, France. [Ma, S.] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Oriol, A.] Hosp Badalona Germans Trias & Pujol, Catala Oncol 9Inst, Barcelona, Spain. [Heffner, L.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Shustik, C.] McGill Univ Hlth Ctr, Royal Victoria Hosp, Montreal, PQ, Canada. [Garcia-Sanz, R.] Hosp Univ Salamanca, Salamanca, Spain. [Cornell, R. F.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Fernandez de Larrea, C.] IDIBAPS, Hosp Clin Barcelona, Barcelona, Spain. [Castillo, J. J.; Treon, S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Granell, M.; Leblond, V.] Hosp Sant Pau, Barcelona, Spain. [Kyrtsonis, M. C.] Univ Athens, Athens 11528, Greece. [Leblond, V.] UPMC Univ Paris, Hop Pitie Salpetriere APHP, Paris, France. [Symeonidis, A.] Univ Patras, Medial Sch, Patras, Greece. [Singh, P.; Li, J.; Graef, T.; Bilotti, E.] AbbVie Co, Pharmacyclics LLC, Sunnyvale, CA USA. [Buske, C.] Univ Hosp Ulm, Inst Expt Canc Res, Comprehens Canc Ctr Ulm, INNOVATE TM Study Grp, Ulm, Germany. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P652 BP 256 EP 257 PG 2 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484601013 ER PT J AU Richardson, PG Hofmeister, CC Raje, NS Siegel, DS Lonial, S Laubach, J Efebera, YA Vesole, DH Nooka, AK Rosenblatt, J Zaki, MH Bensmaine, A Herring, J Li, Y Shah, S Chen, MS Anderson, KC AF Richardson, P. G. Hofmeister, C. C. Raje, N. S. Siegel, D. S. Lonial, S. Laubach, J. Efebera, Y. A. Vesole, D. H. Nooka, A. K. Rosenblatt, J. Zaki, M. H. Bensmaine, A. Herring, J. Li, Y. Shah, S. Chen, M. S. Anderson, K. C. TI POMALIDOMIDE, BORTEZOMIB, AND LOW-DOSE DEXAMETHASONE IN PROTEASOME INHIBITOR-EXPOSED AND LENALIDOMIDE-REFRACTORY MYELOMA: RESULTS OF A MULTICENTER, DOSE-ESCALATION, PHASE 1 TRIAL (MM-005) SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Richardson, P. G.; Laubach, J.; Anderson, K. C.] Harvard Med Sch, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA USA. [Hofmeister, C. C.; Efebera, Y. A.] Ohio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA. [Raje, N. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Siegel, D. S.; Vesole, D. H.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Lonial, S.; Nooka, A. K.] Emory Univ, Div BMT, Winship Canc Inst Hematol & Med Oncol, Atlanta, GA 30322 USA. [Rosenblatt, J.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Zaki, M. H.; Bensmaine, A.; Herring, J.; Li, Y.; Shah, S.; Chen, M. S.] Celgene Corp, Summit, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P653 BP 257 EP 257 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484601014 ER PT J AU Leleu, X Masszi, T Bahlis, NJ Viterbo, L Baker, B Gimsing, P Maisnar, V Samoilova, O Rosinol, L Langer, C Song, K Izumi, T Cleeland, C Berg, D Lin, HM Zhu, Y Skacel, T Jhaveri, M Seal, B Moreau, P Richardson, PG AF Leleu, X. Masszi, T. Bahlis, N. J. Viterbo, L. Baker, B. Gimsing, P. Maisnar, V. Samoilova, O. Rosinol, L. Langer, C. Song, K. Izumi, T. Cleeland, C. Berg, D. Lin, H. M. Zhu, Y. Skacel, T. Jhaveri, M. Seal, B. Moreau, P. Richardson, P. G. TI PATIENT-REPORTED QUALITY OF LIFE WITH IXAZOMIB-LENALIDOMIDE-DEXAMETHASONE (IRD) VS PLACEBO-RD IN RELAPSED/REFRACTORY MULTIPLE MYELOMA PATIENTS IN THE GLOBAL, PLACEBO-CONTROLLED TOURMALINE-MM1 STUDY SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Leleu, X.] Hop Huriez, Lille, France. [Masszi, T.] St Laszlo Hosp, Budapest, Hungary. [Masszi, T.] Semmelweis Univ, Dept Internal Med 3, Budapest, Hungary. [Bahlis, N. J.] Univ Calgary, Southern Alberta Canc Res Inst, Calgary, AB, Canada. [Viterbo, L.] EPE, IPOPFG, Oporto, Portugal. [Baker, B.] Palmerston North Hosp, Palmerston North, Manawatu, New Zealand. [Gimsing, P.] Rigshosp, Univ Hosp, Dept Hematol, Copenhagen, Denmark. [Maisnar, V.] Charles Univ Prague, Fac Med Hradec Kralove, Hradec Kralove, Czech Republic. [Samoilova, O.] Nizhnii Novgorod Reg Clin Hosp, Nizhnii Novgorod, Russia. [Rosinol, L.] Univ Barcelona, Barcelona, Spain. [Langer, C.] Univ Hosp Ulm, Ulm, Germany. [Song, K.] Univ British Columbia, Vancouver, BC, Canada. [Izumi, T.] Tochigi Canc Ctr, Utsunomiya, Tochigi, Japan. [Cleeland, C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Berg, D.; Lin, H. M.; Zhu, Y.; Skacel, T.; Jhaveri, M.; Seal, B.] Millennium Pharmaceut Inc, Cambridge, MA USA. [Moreau, P.] Hop Hotel Dieu, Univ Hosp, Nantes, France. [Richardson, P. G.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI richard, chrystelle/K-8595-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA P660 BP 261 EP 261 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484601021 ER PT J AU Engert, A Santoro, A Shipp, M Zinzani, PL Timmerman, J Ansell, S Armand, P Fanale, M Ratanatharathorn, V Kuruvilla, J Cohen, J Collins, G Savage, K Trneny, M Kato, K Farsaci, B Parker, S Rodig, S Younes, A AF Engert, A. Santoro, A. Shipp, M. Zinzani, P. L. Timmerman, J. Ansell, S. Armand, P. Fanale, M. Ratanatharathorn, V. Kuruvilla, J. Cohen, J. Collins, G. Savage, K. Trneny, M. Kato, K. Farsaci, B. Parker, S. Rodig, S. Younes, A. TI CHECKMATE 205: A PHASE 2 STUDY OF NIVOLUMAB IN PATIENTS WITH CLASSICAL HODGKIN LYMPHOMA FOLLOWING AUTOLOGOUS STEM CELL TRANSPLANTATION AND BRENTUXIMAB VEDOTIN SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Engert, A.] Univ Hosp Cologne, Cologne, Germany. [Santoro, A.] Humanitas Univ, Humanitas Canc Ctr, Milan, Italy. [Shipp, M.; Armand, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zinzani, P. L.] Univ Bologna, Inst Hematol, Bologna, Italy. [Timmerman, J.] Calif State Univ Los Angeles, Los Angeles, CA USA. [Ansell, S.] Mayo Clin, Rochester, MN USA. [Fanale, M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ratanatharathorn, V.] Barbara Ann Karmanos Canc Inst, Detroit, MI USA. [Kuruvilla, J.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Kuruvilla, J.] Univ Toronto, Toronto, ON, Canada. [Cohen, J.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Collins, G.] Churchill Hosp, Oxford Canc & Haematol Ctr, Oxford, England. [Savage, K.] British Columbia Canc Agcy Ctr Lymphoid Canc, Vancouver, BC, Canada. [Trneny, M.] Charles Univ Prague, Prague, Czech Republic. [Trneny, M.] Gen Univ Prague, Prague, Czech Republic. [Kato, K.; Farsaci, B.; Parker, S.] Bristol Myers Squibb, Princeton, NJ USA. [Rodig, S.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Rodig, S.] Dana Farber Canc Inst, Ctr Immuno Oncol, Boston, MA 02115 USA. [Younes, A.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA S793 BP 319 EP 319 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484601155 ER PT J AU Moskowitz, C Zinzani, PL Fanale, MA Armand, P Johnson, N Ribrag, V Radford, J von Tresckow, B Tomita, A Shipp, MA Wang, Y Ricart, AD Balakumaran, A Chen, R AF Moskowitz, C. Zinzani, P. L. Fanale, M. A. Armand, P. Johnson, N. Ribrag, V. Radford, J. von Tresckow, B. Tomita, A. Shipp, M. A. Wang, Y. Ricart, A. D. Balakumaran, A. Chen, R. TI MULTICOHORT PHASE 2 STUDY OF PEMBROLIZUMAB FOR RELAPSED/REFRACTORY CLASSICAL HODGKIN LYMPHOMA (R/R CHL): KEYNOTE-087 SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Moskowitz, C.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Zinzani, P. L.] Univ Bologna, Bologna, Italy. [Fanale, M. A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Armand, P.; Shipp, M. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Johnson, N.] Jewish Gen Hosp, Montreal, PQ, Canada. [Ribrag, V.] Inst Gustave Roussy, Villejuif, France. [Radford, J.] Christie Hosp NHS Fdn Trust, Manchester, Lancs, England. [von Tresckow, B.] Uniklin Koln, Cologne, Germany. [Tomita, A.] Fujita Hlth Univ, Sch Med, Toyoake, Aichi, Japan. [Tomita, A.] Nagoya Univ, Toyoake, Aichi, Japan. [Wang, Y.; Ricart, A. D.; Balakumaran, A.] Merck & Co Inc, Kenilworth, NJ USA. [Chen, R.] City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA. NR 0 TC 1 Z9 1 U1 3 U2 3 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA S794 BP 319 EP 319 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484601156 ER PT J AU Zinzani, PL Ribrag, V Moskowitz, CH Michot, JM Kuruvilla, J Balakumaran, A Thompson, S Marinello, P Chlosta, S Shipp, MA Armand, P AF Zinzani, P. L. Ribrag, V. Moskowitz, C. H. Michot, J. M. Kuruvilla, J. Balakumaran, A. Thompson, S. Marinello, P. Chlosta, S. Shipp, M. A. Armand, P. TI PHASE 1B STUDY OF PEMBROLIZUMAB IN PATIENTS WITH RELAPSED/REFRACTORY PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA: KEYNOTE-013 SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Zinzani, P. L.] Univ Bologna, Bologna, Italy. [Ribrag, V.; Michot, J. M.] Inst Gustave Roussy, Villejuif, France. [Moskowitz, C. H.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Kuruvilla, J.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Kuruvilla, J.] Univ Toronto, Toronto, ON, Canada. [Balakumaran, A.; Thompson, S.; Marinello, P.; Chlosta, S.] Merck & Co Inc, Kenilworth, NJ USA. [Shipp, M. A.; Armand, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA S797 BP 320 EP 321 PG 2 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484601159 ER PT J AU Kuhn, MW Song, E Feng, Z Sinha, A Chen, CW Deshpande, AJ Cusan, M Farnoud, NR Koche, R Bradner, JE de Stanchina, E Vassiliou, GS Hoshii, T Armstrong, SA AF Kuehn, M. W. Song, E. Feng, Z. Sinha, A. Chen, C. W. Deshpande, A. J. Cusan, M. Farnoud, N. Rahnamay Koche, R. Bradner, J. E. de Stanchina, E. Vassiliou, G. S. Hoshii, T. Armstrong, S. A. TI TARGETING CHROMATIN REGULATORS INHIBITS LEUKEMOGENIC GENE EXPRESSION IN NPM1 MUTANT LEUKEMIA SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Kuehn, M. W.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Med 3, Mainz, Germany. [Kuehn, M. W.; Song, E.; Feng, Z.; Sinha, A.; Chen, C. W.; Deshpande, A. J.; Cusan, M.; Farnoud, N. Rahnamay; Koche, R.; Hoshii, T.; Armstrong, S. A.] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, 1275 York Ave, New York, NY 10021 USA. [Bradner, J. E.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. [de Stanchina, E.] Mem Sloan Kettering Canc Ctr, Antitumor Assessment Facil, 1275 York Ave, New York, NY 10021 USA. [Vassiliou, G. S.] Wellcome Trust Sanger Inst, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA S803 BP 323 EP 323 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484601165 ER PT J AU Pemmaraju, N Lane, A Sweet, K Stein, A Vasu, S Blum, W Rizzieri, D Wang, E Duvic, M Chen, J Shemesh, S McDonald, P Brooks, C Kantarjian, H Konopleva, M AF Pemmaraju, N. Lane, A. Sweet, K. Stein, A. Vasu, S. Blum, W. Rizzieri, D. Wang, E. Duvic, M. Chen, J. Shemesh, S. McDonald, P. Brooks, C. Kantarjian, H. Konopleva, M. TI RESULTS FROM ONGOING PHASE 2 REGISTRATION STUDY OF SL-401 IN PATIENTS WITH BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM (BPDCN) SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Pemmaraju, N.; Duvic, M.; Kantarjian, H.; Konopleva, M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Lane, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sweet, K.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Stein, A.] City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA. [Vasu, S.; Blum, W.] Ohio State Univ, Columbus, OH 43210 USA. [Rizzieri, D.] Duke Univ, Med Ctr, Durham, NC USA. [Wang, E.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Chen, J.; Shemesh, S.; McDonald, P.; Brooks, C.] Stemline Therapeut Inc, New York, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA S812 BP 327 EP 327 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484601174 ER PT J AU Raje, N Terpos, E Cole, C Bahlis, N Bensinger, W Libby, E Palumbo, A Lonial, S Sandhu, I Arce-Lara, C Jagannath, S Valent, J Rosko, A Reece, D Supko, J Tamang, D Jones, S Wheeler, C Markelewicz, R Richardson, P AF Raje, N. Terpos, E. Cole, C. Bahlis, N. Bensinger, W. Libby, E. Palumbo, A. Lonial, S. Sandhu, I. Arce-Lara, C. Jagannath, S. Valent, J. Rosko, A. Reece, D. Supko, J. Tamang, D. Jones, S. Wheeler, C. Markelewicz, R. Richardson, P. TI RICOLINOSTAT (ACY-1215), THE FIRST SELECTIVE HDAC6 INHIBITOR, COMBINED WITH POMALIDOMIDE AND DEXAMETHASONE SHOWS PROMISING EARLY PHASE 2 RESULTS IN RELAPSED-AND-REFRACTORY MULTIPLE MYELOMA: ACE-MM-102 SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Raje, N.; Supko, J.; Richardson, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Terpos, E.] Univ Athens, Athens, Greece. [Cole, C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Bahlis, N.] Univ Calgary, Calgary, AB, Canada. [Bensinger, W.; Libby, E.] Univ Washington, Seattle, WA 98195 USA. [Palumbo, A.] Univ Turin, Turin, Italy. [Lonial, S.] Emory Univ, Atlanta, GA 30322 USA. [Sandhu, I.] Univ Alberta, Edmonton, AB T6G 2M7, Canada. [Arce-Lara, C.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Jagannath, S.] Mt Sinai Hosp, New York, NY 10029 USA. [Valent, J.] Cleveland Clin, Cleveland, OH 44106 USA. [Rosko, A.] Ohio State Univ, Columbus, OH 43210 USA. [Reece, D.] Univ Toronto, Toronto, ON, Canada. [Tamang, D.; Jones, S.; Wheeler, C.; Markelewicz, R.] Acetylon Pharmaceut Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA S813 BP 328 EP 328 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484601175 ER PT J AU Richardson, P Wong, E Stockerl-Goldstein, K Rosenbaum, C Dhodapkar, M Jou, YM Lynch, M Robbins, M Bleickardt, E Jagannath, S AF Richardson, P. Wong, E. Stockerl-Goldstein, K. Rosenbaum, C. Dhodapkar, M. Jou, Y. M. Lynch, M. Robbins, M. Bleickardt, E. Jagannath, S. TI A PHASE 2, OPEN-LABEL, MULTICENTER STUDY OF ELOTUZUMAB MONOTHERAPY IN PATIENTS WITH HIGH-RISK SMOLDERING MULTIPLE MYELOMA SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Richardson, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wong, E.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Stockerl-Goldstein, K.] Washington Univ, St Louis, MO USA. [Rosenbaum, C.] Univ Chicago Med, Chicago, IL USA. [Dhodapkar, M.] Yale Univ, New Haven, CT USA. [Jou, Y. M.; Lynch, M.; Robbins, M.; Bleickardt, E.] Bristol Myers Squibb Co, Princeton, NJ USA. [Jagannath, S.] Mt Sinai Med Ctr, New York, NY 10029 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA S815 BP 328 EP 329 PG 2 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484601177 ER PT J AU Kantarjian, HM DeAngelo, DJ Advani, AS Liedtke, M Stock, W Goekbuget, N O'Brien, S Martinelli, G Wang, K Wang, T Pacagnella, ML Sleight, B Vandendries, E Stelljes, M AF Kantarjian, H. M. DeAngelo, D. J. Advani, A. S. Liedtke, M. Stock, W. Goekbuget, N. O'Brien, S. Martinelli, G. Wang, K. Wang, T. Pacagnella, M. L. Sleight, B. Vandendries, E. Stelljes, M. TI OOVERALL SURVIVAL IN RELAPSED/REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS RECEIVING INOTUZUMAB OZOGAMICIN VS STANDARD CARE IN THE PHASE 3 INO-VATE STUDY SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Kantarjian, H. M.] Univ Texas Houston, MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. [DeAngelo, D. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Advani, A. S.] Cleveland Clin, Cleveland, OH 44106 USA. [Liedtke, M.] Stanford Comprehens Canc Ctr, Stanford, CA USA. [Stock, W.] Univ Chicago, Chicaago, IL USA. [Goekbuget, N.] Goethe Univ Frankfurt, Frankfurt, Germany. [O'Brien, S.] Univ Calif Irvine, Orange, CA 92668 USA. [Martinelli, G.] Univ Bologna, Inst Seragnoli, Bologna, Italy. [Wang, K.] Pfizer Inc, Pearl River, NY USA. [Wang, T.; Pacagnella, M. L.; Sleight, B.] Pfizer Inc, Groton, CT 06340 USA. [Vandendries, E.] Pfizer Inc, Cambridge, MA USA. [Stelljes, M.] Univ Klinikum Munster, Munster, Germany. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA LB2233 BP 339 EP 339 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484601200 ER PT J AU Dimopoulos, MA Oriol, A Nahi, H Miguel, JS Bahlis, NJ Rabin, N Orlowski, R Komarnicki, M Suzuki, K Plesner, T Samoilova, OS Yoon, SS Yehuda, DB Richardson, PG Goldschmidt, H Reece, D Khokhar, N O'Rourke, L Chiu, C Qin, X Guckert, M Ahmadi, T Moreau, P AF Dimopoulos, M. A. Oriol, A. Nahi, H. Miguel, J. S. Bahlis, N. J. Rabin, N. Orlowski, R. Komarnicki, M. Suzuki, K. Plesner, T. Samoilova, O. S. Yoon, S. S. Yehuda, D. B. Richardson, P. G. Goldschmidt, H. Reece, D. Khokhar, N. O'Rourke, L. Chiu, C. Qin, X. Guckert, M. Ahmadi, T. Moreau, P. TI This abstract is part of the Presidential Symposium AN OPEN-LABEL, RANDOMISED, PHASE 3 STUDY OF DARATUMUMAB, LENALIDOMIDE, AND DEXAMETHASONE (DRD) VERSUS LENALIDOMIDE AND DEXAMETHASONE (RD) IN RELAPSED OR REFRACTORY MULTIPLE MYELOMA (RRMM): POLLUX SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Dimopoulos, M. A.] Univ Athens, Athens, Greece. [Oriol, A.] HGTiP, Inst Catala Oncol, Barcelona, Spain. [Nahi, H.] Karolinska Inst, Stockholm, Sweden. [Nahi, H.] Karolinska Univ Hosp Huddinge, Div Hematol, Dept Med, Stockholm, Sweden. [Miguel, J. S.] Univ Navarra Clin, CIMA, Pamplona, Spain. [Bahlis, N. J.] Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. [Rabin, N.] Univ Coll London Hosp NHS Trust, Dept Haematol, London, England. [Orlowski, R.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX USA. [Komarnicki, M.] Poznan Univ Med Sci, Dept Hematol & Stem Cell Transplantat, Poznan, Poland. [Suzuki, K.] Japanese Red Cross Med Ctr, Dept Hematol, Tokyo, Japan. [Plesner, T.] Vejle Hosp, Vejle, Denmark. [Plesner, T.] Univ Southern Denmark, Vejle, Denmark. [Samoilova, O. S.] Nizhny Novgorod Reg Clin Hosp, Nizhnii Novgorod, Russia. [Yoon, S. S.] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul, South Korea. [Yehuda, D. B.] Hadassah Hebrew Univ Med Ctr, Hematol Dept, Jerusalem, Israel. [Richardson, P. G.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. [Goldschmidt, H.] Univ Hosp Heidelberg, Heidelberg, Germany. [Goldschmidt, H.] German Canc Res Ctr, Heidelberg, Germany. [Reece, D.] Princess Margaret Canc Ctr, CCRU, Toronto, ON, Canada. [Khokhar, N.; O'Rourke, L.; Chiu, C.; Guckert, M.; Ahmadi, T.] Janssen Res & Dev, Spring House, PA USA. [Qin, X.] Janssen Res & Dev, Horsham, PA USA. [Moreau, P.] Univ Hosp Hotel Dieu, Hematol, Nantes, France. RI richard, chrystelle/K-8595-2015 NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA LB2238 BP 342 EP 342 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484601205 ER PT J AU Kernan, N Richardson, P Smith, A Triplett, B Grupp, S Antin, J Lehmann, L Messinger, Y Liang, W Hume, R Hannah, A Soiffer, R AF Kernan, N. Richardson, P. Smith, A. Triplett, B. Grupp, S. Antin, J. Lehmann, L. Messinger, Y. Liang, W. Hume, R. Hannah, A. Soiffer, R. TI EFFICACY AND SAFETY OF DEFIBROTIDE FOR TREATMENT OF HEPATIC VENO-OCCLUSIVE DISEASE/SINUSOIDAL OBSTRUCTION SYNDROME (VOD/SOS) IN ADULT AND PEDIATRIC PATIENTS FOLLOWING CHEMOTHERAPY SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Kernan, N.] Mem Sloan Kettering Canc Ctr, Pediat BMT Serv, 1275 York Ave, New York, NY 10021 USA. [Richardson, P.] Harvard Med Sch, Jerome Lipper Multiple Myeloma Ctr, Div Hematol Malignancy, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA USA. [Smith, A.] Univ Minnesota, Div Pediat Blood & Marrow Transplantat, Minneapolis, MN USA. [Triplett, B.] St Jude Childrens Res Hosp, Bone Marrow Transplantat & Cellular Therapy, 332 N Lauderdale St, Memphis, TN 38105 USA. [Grupp, S.] Childrens Hosp Philadelphia, Pediat Oncol, Philadelphia, PA 19104 USA. [Antin, J.; Soiffer, R.] Harvard Med Sch, Dana Farber Canc Inst, Stem Cell Bone Marrow Transplantat Program, Div Hematol Malignancy,Dept Med Oncol, Boston, MA USA. [Lehmann, L.] Harvard Med Sch, Dana Farber Canc Inst, Ctr Stem Cell Transplantat, Div Hematol Malignancy,Dept Med Oncol, Boston, MA USA. [Messinger, Y.] Childrens Minnesota, Canc & Blood Disorders Program, Minneapolis, MN USA. [Liang, W.; Hume, R.; Hannah, A.] Jazz Pharmaceut, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA E1012 BP 414 EP 414 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484601385 ER PT J AU Carra, G Panuzzo, C Crivellaro, S Torti, D Parvis, G Familiari, U Volante, M Morena, D Lingua, MF Brancaccio, M Guerrasio, A Pandolfi, PP Saglio, G Taulli, R Morotti, A AF Carra, G. Panuzzo, C. Crivellaro, S. Torti, D. Parvis, G. Familiari, U. Volante, M. Morena, D. Lingua, M. F. Brancaccio, M. Guerrasio, A. Pandolfi, P. P. Saglio, G. Taulli, R. Morotti, A. TI INHIBITION OF USP7 INDUCES SELECTIVE CANCER CELL DEATH IN CHRONIC LYMPHOCYTIC LEUKEMIA THROUGH PTEN AND INDEPENDENTLY FROM P53 STATUS SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Carra, G.; Panuzzo, C.; Crivellaro, S.; Guerrasio, A.; Saglio, G.; Morotti, A.] San Luigi Gonzaga Hosp, Dept Clin & Biol Sci, Orbassano, Italy. [Torti, D.; Parvis, G.] San Luigi Gonzaga Hosp, Hematol, Div Internal Med, Orbassano, Italy. [Familiari, U.; Volante, M.] San Luigi Gonzaga Hosp, Div Pathol, Orbassano, Italy. [Volante, M.; Morena, D.; Lingua, M. F.; Taulli, R.] Univ Turin, San Luigi Gonzaga Hosp, Div Pathol, Dept Oncol, Orbassano, Italy. [Brancaccio, M.] Univ Turin, Dept Mol Biotechnol & Hlth Sci, Turin, Italy. [Pandolfi, P. P.] Harvard Med Sch, Canc Genet Program, Beth Israel Deaconess Canc Ctr, Dept Med & Pathol,Beth Israel Deaconess Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA E1024 BP 421 EP 421 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484601401 ER PT J AU Davids, MS Kim, HT Nicotra, A Savell, A Francoeur, K Hellman, JM Miskin, H Sportelli, P Rado, T Bashey, A Stampleman, L Rueter, J Boruchov, A Arnason, JE Jacobson, CA Fisher, DC Brown, JR AF Davids, M. S. Kim, H. T. Nicotra, A. Savell, A. Francoeur, K. Hellman, J. M. Miskin, H. Sportelli, P. Rado, T. Bashey, A. Stampleman, L. Rueter, J. Boruchov, A. Arnason, J. E. Jacobson, C. A. Fisher, D. C. Brown, J. R. TI PRELIMINARY RESULTS OF A PHASE I/IB STUDY OF IBRUTINIB IN COMBINATION WITH TGR-1202 IN PATIENTS WITH RELAPSED/REFRACTORY CLL OR MCL SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Davids, M. S.; Kim, H. T.; Nicotra, A.; Savell, A.; Francoeur, K.; Hellman, J. M.; Jacobson, C. A.; Fisher, D. C.; Brown, J. R.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Miskin, H.; Sportelli, P.] TG Therapeut, New York, NY USA. [Rado, T.] Kadlec Clin Hematol & Oncol, Kennewick, WA USA. [Bashey, A.] Bone Marrow Transplantat Grp Georgia, Atlanta, GA USA. [Stampleman, L.] Pacific Canc Care, Salinas, CA USA. [Rueter, J.] Eastern Maine Med Ctr, Bangor, ME USA. [Boruchov, A.] St Francis Med Ctr, Hartford, CT USA. [Arnason, J. E.] Beth Israel Deaconess Med Ctr, Med Oncol, Boston, MA 02215 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA E1053 BP 433 EP 433 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484601431 ER PT J AU Robak, T Zelenetz, AD Mato, A Jones, JA Pagel, JM Barrientos, JC Brown, JR Montillo, M Dubowy, R Xing, G Li, JJ Kipps, TJ Hillmen, P AF Robak, T. Zelenetz, A. D. Mato, A. Jones, J. A. Pagel, J. M. Barrientos, J. C. Brown, J. R. Montillo, M. Dubowy, R. Xing, G. Li, J. J. Kipps, T. J. Hillmen, P. TI IDELALISIB PLUS AN ANTI-CD20 ANTIBODY IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) WHO ARE HBV CORE ANTIBODY POSITIVE: SIMILAR PATTERNS OF LIVER TEST ABNORMALITIES SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc ID HEPATITIS-B; REACTIVATION; RITUXIMAB C1 [Robak, T.] Med Univ Lodz, Lodz, Poland. [Zelenetz, A. D.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Mato, A.] Hosp Univ Penn, Ctr CLL, 3400 Spruce St, Philadelphia, PA 19104 USA. [Jones, J. A.] Ohio State Univ, Columbus, OH 43210 USA. [Pagel, J. M.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Barrientos, J. C.] Hofstra Northwell Sch Med, Hempstead, NY USA. [Brown, J. R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Montillo, M.] Osped Niguarda Ca Granda, Milan, Italy. [Dubowy, R.; Xing, G.; Li, J. J.] Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA. [Kipps, T. J.] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA. [Hillmen, P.] St James Univ Hosp, Leeds, W Yorkshire, England. NR 4 TC 0 Z9 0 U1 1 U2 2 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA E1063 BP 437 EP 437 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484601440 ER PT J AU Ghia, P Cheson, BD Furman, RR Hallek, M Hillmen, P O'Brien, SM Sharman, JP Dubowy, RL Velasco, B Waldapfel, CC Zelenetz, AD Brown, JR AF Ghia, P. Cheson, B. D. Furman, R. R. Hallek, M. Hillmen, P. O'Brien, S. M. Sharman, J. P. Dubowy, R. L. Velasco, B. Waldapfel, C. C. Zelenetz, A. D. Brown, J. R. TI PATTERNS OF IDELALISIB TREATMENT-EMERGENT LYMPHOCYTOSIS IN PATIENTS WITH CLL OR SLL SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Ghia, P.] Univ Vita Salute San Raffaele, Milan, Italy. [Ghia, P.] IRCCS Inst Sci San Raffaele, Milan, Italy. [Cheson, B. D.] Georgetown Univ Hosp, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Furman, R. R.] New York Presbyterian Weill Cornell Med Ctr, New York, NY USA. [Hallek, M.] Univ Hosp, Dept Internal Med, Cologne, Germany. [Hallek, M.] Univ Hosp, Ctr Integrated Oncol Cologne Bonn, Cologne, Germany. [Hillmen, P.] St James Univ Hosp, Haematol, Leeds, W Yorkshire, England. [O'Brien, S. M.] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Orange, CA 92668 USA. [Sharman, J. P.] US Oncol Network, Willamette Valley Canc Inst, Springfield, OR USA. [Dubowy, R. L.; Velasco, B.; Waldapfel, C. C.] Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA. [Zelenetz, A. D.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Brown, J. R.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA E1067 BP 439 EP 439 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484601444 ER PT J AU Gkotzamanidou, M Terpos, E Munshi, NC Dimopoulos, MA Souliotis, VL AF Gkotzamanidou, M. Terpos, E. Munshi, N. C. Dimopoulos, M. A. Souliotis, V. L. TI DEREGULATION OF MAJOR DNA REPAIR MECHANISMS CORRELATES WITH CLINICAL OUTCOME OF ANTI-MYELOMA THERAPY. THE BENEFICIAL EFFECT OF DNA REPAIR INHIBITION SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Gkotzamanidou, M.; Munshi, N. C.] Harvard Med Sch, Dana Farber Canc Inst, Med Oncol, Boston, MA USA. [Terpos, E.; Dimopoulos, M. A.] Univ Athens, Sch Med, Dept Clin Therapeut, Athens, Greece. [Souliotis, V. L.] Natl Hellen Res Fdn, Biol Med Chem & Biotechnol 3Inst, Athens, Greece. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA E1238 BP 511 EP 511 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484602027 ER PT J AU Kuter, D Cook, G Goldschmidt, H Cella, D Zyczynski, T Davis, C Popov, S Vij, R AF Kuter, D. Cook, G. Goldschmidt, H. Cella, D. Zyczynski, T. Davis, C. Popov, S. Vij, R. TI AN ONGOING MULTINATIONAL OBSERVATIONAL STUDY IN MULTIPLE MYELOMA (PREAMBLE): PRELIMINARY REPORT ON PROGRESSION-FREE SURVIVAL SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Kuter, D.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol, Boston, MA USA. [Cook, G.] Univ Leeds, Sect Expt Haematol, Leeds, W Yorkshire, England. [Goldschmidt, H.] Univ Heidelberg Hosp, Hematol & Oncol, Heidelberg, Germany. [Cella, D.] Northwestern Univ, Dept Med Social Sci, Evanston, IL USA. [Zyczynski, T.] Bristol Myers Squibb Co, Worldwide Hlth Econ & Outcomes Res, Princeton, NJ USA. [Davis, C.; Popov, S.] Parexel, Biostat, St Petersburg, Russia. [Vij, R.] Washington Univ, Sch Med, Div Med Oncol, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA E1261 BP 520 EP 520 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484602050 ER PT J AU Niesvizky, R Richardson, P Gabrail, N Madan, S Yee, A Shain, K Hoffman, J Pagel, J Bensinger, W Nooka, A Agarwal, A Matous, J Raab, MS Terpos, E Bhol, K Tamang, D Jones, SS van Duzer, J Wheeler, C Trede, NS Raje, N AF Niesvizky, R. Richardson, P. Gabrail, N. Madan, S. Yee, A. Shain, K. Hoffman, J. Pagel, J. Bensinger, W. Nooka, A. Agarwal, A. Matous, J. Raab, M. S. Terpos, E. Bhol, K. Tamang, D. Jones, S. S. van Duzer, J. Wheeler, C. Trede, N. S. Raje, N. TI ACY-241, A NOVEL, ORAL TABLET HDAC6 SELECTIVE INHIBITOR COMBINES SAFELY WITH POMALIDOMIDE AND DEXAMETHASONE IN PATIENTS WITH RELAPSED OR RELAPSED AND REFRACTORY MULTIPLE MYELOMA (ACE-MM-200 STUDY) SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Niesvizky, R.] Weill Cornell Med Coll, New York, NY USA. [Richardson, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gabrail, N.] Gabrail Canc Ctr, Canton, OH USA. [Madan, S.] Canc Therapy & Res Ctr S Texas, San Antonio, TX USA. [Yee, A.; Raje, N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shain, K.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Hoffman, J.] Univ Miami, Ctr Canc, Miami, FL USA. [Pagel, J.; Bensinger, W.] Swedish Canc Inst, Seattle, WA USA. [Nooka, A.] Emory Univ, Atlanta, GA 30322 USA. [Agarwal, A.] Univ Arizona, Ctr Canc, Tucson, AZ USA. [Matous, J.] Colorado Blood Canc Inst, Denver, CO USA. [Raab, M. S.] Heidelberg Univ, Heidelberg, Germany. [Terpos, E.] Univ Athens, Athens, Greece. [Bhol, K.; Tamang, D.; Jones, S. S.; van Duzer, J.; Wheeler, C.; Trede, N. S.] Acetylon Pharmaceut Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA E1270 BP 524 EP 525 PG 2 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484602059 ER PT J AU Liu, D Manier, S Laubach, J Van Allen, EM Ghobrial, I AF Liu, D. Manier, S. Laubach, J. Van Allen, E. M. Ghobrial, I. TI TREATMENT OF PRE-MYELOMA STATES: A CLINICAL DECISION ANALYSIS SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Liu, D.] Massachusetts Gen Hosp, Med Oncol, Cambridge, MA USA. [Liu, D.; Manier, S.; Laubach, J.; Van Allen, E. M.; Ghobrial, I.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Liu, D.; Van Allen, E. M.] Broad Inst, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA E1271 BP 525 EP 525 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484602060 ER PT J AU Mateos, MV Masszi, T Grzasko, N Hansson, M Sandhu, I Pour, L Viterbo, L Jackson, S Stoppa, AM Gimsing, P Hamadani, M Borsaru, G Berg, D Lin, J van de Velde, H Richardson, P Moreau, P AF Mateos, M. V. Masszi, T. Grzasko, N. Hansson, M. Sandhu, I. Pour, L. Viterbo, L. Jackson, S. Stoppa, A. M. Gimsing, P. Hamadani, M. Borsaru, G. Berg, D. Lin, J. van de Velde, H. Richardson, P. Moreau, P. TI EFFICACY AND SAFETY OF ORAL IXAZOMIB-LENALIDOMIDE-DEXAMETHASONE (IRD) VS PLACEBO-RD IN RELAPSED/REFRACTORY MULTIPLE MYELOMA PATIENTS: IMPACT OF PRIOR THERAPY IN THE PHASE 3 TOURMALINE-MM1 STUDY SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Mateos, M. V.] Hosp Univ Salamanca, Inst Biosanitario Salamanca IBSAL, Serv Hematol, Salamanca, Spain. [Masszi, T.] St Istvan & St Laszlo Hosp, Dept Med 3, Budapest, Hungary. [Grzasko, N.] Med Univ Lublin, Lublin, Poland. [Grzasko, N.] St Johns Canc Ctr, Lublin, Poland. [Hansson, M.] Lund Univ, Skane Univ Hosp, Lund, Sweden. [Sandhu, I.] Univ Alberta, Edmonton, AB, Canada. [Pour, L.] Univ Hosp Brno, Brno, Czech Republic. [Viterbo, L.] EPE, IPOPFG, Oporto, Portugal. [Jackson, S.] Middlemore Hosp, Auckland, New Zealand. [Stoppa, A. M.] Inst Paoli Calmettes, Marseille, France. [Gimsing, P.] Rigshosp, Univ Hosp, Copenhagen, Denmark. [Hamadani, M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Borsaru, G.] Spitalul Clin Coltea, Bucharest, Romania. [Berg, D.; Lin, J.; van de Velde, H.] Millennium Pharmaceut Inc, Cambridge, MA USA. [Richardson, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Moreau, P.] Univ Hosp Hotel Dieu, Nantes, France. RI richard, chrystelle/K-8595-2015 NR 0 TC 0 Z9 0 U1 2 U2 3 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA E1276 BP 527 EP 527 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484602065 ER PT J AU Moreau, P Dimopoulos, MA Richardson, PG Siegel, D Palumbo, A Cavo, M Corradini, P Weisel, K Delforge, M O'Gorman, P Song, K Sternas, L Biyukov, T Hong, K Herring, J Yu, X Zaki, MH San Miguel, J AF Moreau, P. Dimopoulos, M. A. Richardson, P. G. Siegel, D. Palumbo, A. Cavo, M. Corradini, P. Weisel, K. Delforge, M. O'Gorman, P. Song, K. Sternas, L. Biyukov, T. Hong, K. Herring, J. Yu, X. Zaki, M. H. San Miguel, J. TI MANAGEMENT OF ADVERSE EVENTS IN PATIENTS WITH RELAPSED AND REFRACTORY MULTIPLE MYELOMA TREATED WITH POMALIDOMIDE PLUS LOW-DOSE DEXAMETHASONE: A POOLED SAFETY ANALYSIS OF 3 CLINICAL TRIALS SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Moreau, P.] Univ Hosp Hotel Dieu, Nantes, France. [Dimopoulos, M. A.] Univ Athens, Athens, Greece. [Richardson, P. G.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. [Siegel, D.] John Theurer Canc Ctr, Hackensack, NJ USA. [Palumbo, A.] Univ Turin, Turin, Italy. [Cavo, M.] Univ Bologna, Sch Med, Seragnoli Inst Hematol, Bologna, Italy. [Corradini, P.] Univ Milan, Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Weisel, K.] Univ Hosp Tubingen, Tubingen, Germany. [Delforge, M.] Univ Hosp Leuven, Leuven, Belgium. [O'Gorman, P.] Univ Coll Dublin, Mater Misericordiae Univ Hosp, Dublin, Ireland. [Song, K.] Vancouver Gen Hosp, Vancouver, BC, Canada. [Sternas, L.; Hong, K.; Herring, J.; Yu, X.; Zaki, M. H.] Celgene Corp, Summit, NJ USA. [Biyukov, T.] Celgene Int Sarl, Boudry, Switzerland. [San Miguel, J.] Univ Navarra Clin, CIMA, IDISNA, Pamplona, Spain. RI richard, chrystelle/K-8595-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA E1284 BP 531 EP 531 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484602073 ER PT J AU Palumbo, A Dimopoulos, MA Richardson, PG Siegel, DS Cavo, M Corradini, P Weisel, KC Delforge, M Chen, C Goldschmidt, H Jagannath, S Lockhorst, HM Moreau, P Plesner, T Sternas, L Peluso, T Hong, K Herring, J Yu, X Zaki, MH San Miguel, J AF Palumbo, A. Dimopoulos, M. A. Richardson, P. G. Siegel, D. S. Cavo, M. Corradini, P. Weisel, K. C. Delforge, M. Chen, C. Goldschmidt, H. Jagannath, S. Lockhorst, H. M. Moreau, P. Plesner, T. Sternas, L. Peluso, T. Hong, K. Herring, J. Yu, X. Zaki, M. H. San Miguel, J. TI A POOLED ANALYSIS OF THE IMPACT OF AGE ON OUTCOMES IN PATIENTS WITH REFRACTORY OR RELAPSED AND REFRACTORY MULTIPLE MYELOMA TREATED WITH POMALIDOMIDE plus LOW-DOSE DEXAMETHASONE SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Palumbo, A.] Univ Turino, Turin, Italy. [Dimopoulos, M. A.] Univ Athens, Athens, Greece. [Richardson, P. G.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. [Siegel, D. S.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Cavo, M.] Univ Bologna, Sch Med, Seragnoli Inst Hematol, Bologna, Italy. [Corradini, P.] Univ Milan, Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Weisel, K. C.] Univ Hosp Tuebingen, Tubingen, Germany. [Delforge, M.] Univ Hosp Leuven, Leuven, Belgium. [Chen, C.] Princess Margaret Hosp, Toronto, ON, Canada. [Goldschmidt, H.] Univ Hosp Heidelberg, Heidelberg, Germany. [Goldschmidt, H.] German Canc Res Ctr, Heidelberg, Germany. [Jagannath, S.] Mt Sinai Hosp, New York, NY 10029 USA. [Lockhorst, H. M.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Moreau, P.] Univ Hosp Hotel Dieu, Nantes, France. [Peluso, T.] Univ Southern Denmark, Dept Hematol, Ctr Little Belt, Vejle Hosp, Vejle, Denmark. [Sternas, L.; Hong, K.; Herring, J.; Yu, X.; Zaki, M. H.] Celgene Corp, Summit, NJ USA. [Peluso, T.] Celgene Int Sarl, Boudry, Switzerland. [San Miguel, J.] Univ Navarra Clin, CIMA, IDISNA, Pamplona, Spain. RI richard, chrystelle/K-8595-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA E1295 BP 535 EP 536 PG 2 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484602084 ER PT J AU Hou, J Jin, J Xu, Y Wu, D Ke, X Daobin, Z Lu, J Du, X Chen, X Li, J Liu, J Wang, B Zhang, X Wang, H van de Velde, H Richardson, P Moreau, P AF Hou, J. Jin, J. Xu, Y. Wu, D. Ke, X. Daobin, Z. Lu, J. Du, X. Chen, X. Li, J. Liu, J. Wang, B. Zhang, X. Wang, H. van de Velde, H. Richardson, P. Moreau, P. TI IXAZOMIB PLUS LENALIDOMIDE-DEXAMETHASONE (IRD) VS PLACEBO-RD IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM): CHINA CONTINUATION OF TOURMALINE-MM1 SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Hou, J.] Second Mil Med Univ, ChangZheng Hosp, Dept Hematol, Shanghai, Peoples R China. [Jin, J.] Zhe Jiang Med Univ, Hosp 1, Hangzhou, Zhejiang, Peoples R China. [Xu, Y.] Chinese Acad Med Sci, Inst Hematol, Tianjin, Peoples R China. [Xu, Y.] Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China. [Xu, Y.] Peking Union Med Coll, Tianjin, Peoples R China. [Wu, D.] Soochow Univ, Affiliated Hosp 1, Suzhou, Peoples R China. [Ke, X.] Beijing Med Univ, Affiliated Hosp 3, Beijing, Peoples R China. [Daobin, Z.] Beijing Union Med Coll Hosp, Beijing, Peoples R China. [Lu, J.] Peking Univ Peoples Hosp, Beijing, Peoples R China. [Du, X.] Guangdong Acad Med Sci, Guangdong Gen Hosp, Guangzhou, Guangdong, Peoples R China. [Chen, X.] Fourth Mil Med Univ, Xijing Hosp, Xian, Peoples R China. [Li, J.] Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai, Peoples R China. [Liu, J.] Xiang Ya Med Univ, Hosp 3, Changsha, Hunan, Peoples R China. [Wang, B.; Zhang, X.; Wang, H.; van de Velde, H.] Millennium Pharmaceut Inc, Cambridge, MA USA. [Richardson, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Moreau, P.] Univ Hosp Hotel Dieu, Nantes, France. RI richard, chrystelle/K-8595-2015 NR 0 TC 0 Z9 0 U1 3 U2 4 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA E1305 BP 540 EP 540 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484602094 ER PT J AU Roccaro, A Sacco, A Shi, J Chiarini, M Perilla-Glen, A Manier, S Glavey, S Aljaway, Y Mishima, Y Kawano, Y Moschetta, M Correll, M Imberti, L Rossi, G Freedman, M Improgo, MR Castillo, JJ Treon, S Brown, J Van Allen, E Hide, W Hiller, E Rainville, I Ghobrial, I AF Roccaro, A. Sacco, A. Shi, J. Chiarini, M. Perilla-Glen, A. Manier, S. Glavey, S. Aljaway, Y. Mishima, Y. Kawano, Y. Moschetta, M. Correll, M. Imberti, L. Rossi, G. Freedman, M. Improgo, M. R. Castillo, J. J. Treon, S. Brown, J. Van Allen, E. Hide, W. Hiller, E. Rainville, I. Ghobrial, I. TI EXOME SEQUENCING REVEALS RECURRENT GERMLINE VARIANTS IN PATIENTS WITH FAMILIAL LYMPHOPLASMACYTIC LYMPHOMA SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Roccaro, A.; Rossi, G.] Spedali Civili Brescia, CREA Lab, Hematol, Brescia, Italy. [Sacco, A.; Shi, J.; Perilla-Glen, A.; Manier, S.; Glavey, S.; Aljaway, Y.; Mishima, Y.; Kawano, Y.; Moschetta, M.; Correll, M.; Freedman, M.; Improgo, M. R.; Castillo, J. J.; Treon, S.; Brown, J.; Van Allen, E.; Hide, W.; Hiller, E.; Rainville, I.; Ghobrial, I.] Dana Farber Canc Inst, Med Oncol, Boston, MA USA. [Chiarini, M.; Imberti, L.] Spedali Civili Brescia, CREA Lab, Brescia, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA E1371 BP 567 EP 568 PG 2 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484602159 ER PT J AU Lubberts, B Pereira, NRP Kabrhel, C Kuter, D DiGiovanni, C AF Lubberts, B. Pereira, N. R. Paulino Kabrhel, C. Kuter, D. DiGiovanni, C. TI WHAT IS THE EFFECT OF VENOUS THROMBOEMBOLISM AND POST-THROMBOTIC SYNDROME ON HEALTH-RELATED QUALITY OF LIFE? A SYSTEMATIC REVIEW AND META-ANALYSIS SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Lubberts, B.; Pereira, N. R. Paulino; DiGiovanni, C.] Massachusetts Gen Hosp, Orthopaed Surg, Boston, MA 02114 USA. [Kabrhel, C.] Massachusetts Gen Hosp, Emergency Med, Boston, MA 02114 USA. [Kuter, D.] Massachusetts Gen Hosp, Clin Hematol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA E1444 BP 597 EP 597 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484602234 ER PT J AU Richardson, PG Hungria, V Yoon, SS Beksac, M Dimopoulos, MA Elghandour, A Jedrzejczak, WW Jedrzejczak, WW Nakorn, TN Siritanaratkul, N Schlossman, R Hou, J Moreau, P Lonial, S Lee, JH Einsele, H Binlich, F Sopala, M Roy, A Panneerselvam, A San Miguel, J AF Richardson, P. G. Hungria, V. Yoon, S. S. Beksac, M. Dimopoulos, M. A. Elghandour, A. Jedrzejczak, W. W. Jedrzejczak, W. W. Nakorn, T. N. Siritanaratkul, N. Schlossman, R. Hou, J. Moreau, P. Lonial, S. Lee, J. H. Einsele, H. Binlich, F. Sopala, M. Roy, A. Panneerselvam, A. San Miguel, J. TI PATIENT REPORTED OUTCOMES (PROS) OF MULTIPLE MYELOMA (MM) PATIENTS FROM THE PANORAMA-1 STUDY WHO HAVE RECEIVED AT LEAST TWO PRIOR REGIMENS INCLUDING BORTEZOMIB AND AN IMMUNOMODULATORY AGENT SO HAEMATOLOGICA LA English DT Meeting Abstract CT 21st Congress of the European-Hematology-Association CY JUN 09-12, 2016 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Richardson, P. G.; Schlossman, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hungria, V.] Irmandade Santa Casa Misericordia Sao Paulo, Sao Paulo, Brazil. [Yoon, S. S.] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Beksac, M.] Ankara Univ, Sch Med, Ankara, Turkey. [Dimopoulos, M. A.] Univ Athens, Athens, Greece. [Elghandour, A.] Univ Alexandria, Alexandria, Egypt. [Jedrzejczak, W. W.] Med Univ Warsaw, Warsaw, Poland. [Jedrzejczak, W. W.] Univ Hosp Schleswig Holstein, Dept Med 2, Div Stem Cell Transplantat & Immunotherapy, Kiel, Germany. [Jedrzejczak, W. W.] Univ Kiel, Kiel, Germany. [Nakorn, T. N.] King Chulalongkorn Mem Hosp, Bangkok, Thailand. [Nakorn, T. N.] Chulalongkorn Univ, Bangkok, Thailand. [Siritanaratkul, N.] Siriraj Hosp, Bangkok, Thailand. [Hou, J.] Chang Zheng Hosp, Shanghai, Peoples R China. [Moreau, P.] Univ Hosp Nantes, Nantes, France. [Lonial, S.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Lee, J. H.] Gachon Univ, Dept Internal Med, Gil Hosp, Inchon, South Korea. [Einsele, H.] Univ Wurzburg, Med Klin & Poliklin 2, Wurzburg, Germany. [Binlich, F.] Novartis Pharma SAS, Rueil Malmaison, France. [Sopala, M.] Novartis Pharma AG, Basel, Switzerland. [Roy, A.] Novartis Pharmaceut, E Hanover, NJ USA. [Panneerselvam, A.] Novartis Pharmaceut, Florham Pk, NJ USA. [San Miguel, J.] Clin Univ Navarra, Inst Invest Sanitaria Navarra, Ctr Invest Med Aplicada, Pamplona, Spain. RI richard, chrystelle/K-8595-2015 NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 SU 1 MA PB1957 BP 786 EP 786 PG 1 WC Hematology SC Hematology GA DQ8TS UT WOS:000379484603098 ER PT J AU Doyle, BJ Nuckols, TK AF Doyle, Brian J. Nuckols, Teryl K. TI In Reference to "Patient Financial Responsibility for Observation Care" and "Observation Versus Inpatient Hospitalization: What do Medicare Beneficiaries Pay?" SO JOURNAL OF HOSPITAL MEDICINE LA English DT Letter C1 [Doyle, Brian J.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Doyle, Brian J.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Nuckols, Teryl K.] Cedars Sinai Med Ctr, Dept Med, Div Gen Internal Med, Los Angeles, CA 90048 USA. [Nuckols, Teryl K.] RAND Corp, Santa Monica, CA USA. RP Doyle, BJ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA.; Doyle, BJ (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. OI Doyle, Brian/0000-0003-2782-2306 NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD JUN PY 2016 VL 11 IS 6 BP 457 EP 457 DI 10.1002/jhm.2562 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DR6VW UT WOS:000380040400012 PM 26914288 ER PT J AU Tam, JM Mansour, MK Acharya, M Sokolovska, A Timmons, AK Lacy-Hulbert, A Vyas, JM AF Tam, Jenny M. Mansour, Michael K. Acharya, Mridu Sokolovska, Anna Timmons, Allison K. Lacy-Hulbert, Adam Vyas, Jatin M. TI The Role of Autophagy-Related Proteins in Candida albicans Infections SO PATHOGENS LA English DT Review DE autophagy; LC3-associated phagocytosis (LAP); Candida albicans; Aspergillus fumigatus; LC3; innate immunity; Dectin-1 ID CHRONIC GRANULOMATOUS-DISEASE; ASPERGILLUS-FUMIGATUS PHAGOSOMES; PLASMACYTOID DENDRITIC CELLS; REACTIVE OXYGEN PRODUCTION; TOLL-LIKE RECEPTORS; CHAIN 3 PROTEIN; NONCANONICAL AUTOPHAGY; INFLAMMATORY RESPONSES; DECTIN-1; IMMUNITY AB Autophagy plays an important role in maintaining cell homeostasis by providing nutrients during periods of starvation and removing damaged organelles from the cytoplasm. A marker in the autophagic process is the reversible conjugation of LC3, a membrane scaffolding protein, to double membrane autophagosomes. Recently, a role for LC3 in the elimination of pathogenic bacteria and fungi, including Candida albicans (C. albicans), was demonstrated, but these organisms reside in single membrane phagosomes. This process is distinct from autophagy and is termed LC3-associated phagocytosis (LAP). This review will detail the hallmarks of LAP that distinguish it from classical autophagy and review the role of autophagy proteins in host response to C. albicans and other pathogenic fungi. C1 [Tam, Jenny M.; Mansour, Michael K.; Sokolovska, Anna; Timmons, Allison K.; Vyas, Jatin M.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Acharya, Mridu; Lacy-Hulbert, Adam] Benaroya Res Inst, Program Immunol, Seattle, WA 98101 USA. RP Vyas, JM (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. EM jmtam@mgh.harvard.edu; mkmansour@mgh.harvard.edu; macharya@benaroyaresearch.org; anyasokol@gmail.com; atimmons1@mgh.harvard.edu; adamlh@benaroyaresearch.org; jvyas@mgh.harvard.edu RI Vyas, Jatin/Q-1627-2016 OI Vyas, Jatin/0000-0002-9985-9565 NR 75 TC 0 Z9 0 U1 2 U2 2 PU MDPI AG PI BASEL PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND SN 2076-0817 J9 PATHOGENS JI Pathogens PD JUN PY 2016 VL 5 IS 2 AR 34 DI 10.3390/pathogens5020034 PG 14 WC Microbiology SC Microbiology GA DR6WW UT WOS:000380043000001 ER PT J AU Zerillo, J Schouwenburg, M van Bommel, A Stowell, C Van de Velde, C Tollenaar, R AF Zerillo, J. Schouwenburg, M. van Bommel, A. Stowell, C. Van de Velde, C. Tollenaar, R. TI An international patient-centered outcome measurement set for colorectal cancer SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 18th World Congress of the European-Society-for-Medical-Oncology (ESMO) on Gastrointestinal Cancer CY JUN 29-JUL 02, 2016 CL Barcelona, SPAIN SP European Soc Med Oncol C1 [Zerillo, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schouwenburg, M.; van Bommel, A.; Van de Velde, C.; Tollenaar, R.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Stowell, C.] Int Consortium Hlth Outcomes Measurement, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2016 VL 27 SU 2 MA P-131 BP 38 EP 39 PG 2 WC Oncology SC Oncology GA DR2TG UT WOS:000379756200126 ER PT J AU Manish, S Jaafar, B Lin, S Peter, E Qiao, L Ildiko, C Minori, K Toshihiko, D AF Manish, Shah Jaafar, Bennouna Lin, Shen Peter, Enzinger Qiao, Li Ildiko, Csiki Minori, Koshiji Toshihiko, Doi TI Pembrolizumab for patients with previously treated metastatic adenocarcinoma or squamous cell carcinoma of the esophagus: phase 2 KEYNOTE-180 study SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 18th World Congress of the European-Society-for-Medical-Oncology (ESMO) on Gastrointestinal Cancer CY JUN 29-JUL 02, 2016 CL Barcelona, SPAIN SP European Soc Med Oncol C1 [Manish, Shah] Weill Cornell Med Coll, New York, NY USA. [Manish, Shah] New York Presbyterian Hosp, New York, NY USA. [Jaafar, Bennouna] Inst Cancerol Ouest, Nantes, France. [Lin, Shen] Peking Univ, Canc Hosp & Inst, Beijing, Peoples R China. [Peter, Enzinger] Dana Farber Canc Inst, Boston, MA 02115 USA. [Qiao, Li; Ildiko, Csiki; Minori, Koshiji] Merck & Co Inc, Kenilworth, NJ USA. [Toshihiko, Doi] Natl Canc Ctr Hosp East, Kashiwa, Chiba, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2016 VL 27 SU 2 MA P-279 BP 81 EP 81 PG 1 WC Oncology SC Oncology GA DR2TG UT WOS:000379756200270 ER PT J AU Toshihiko, D Jaafar, B Lin, S Peter, E Wang, RX Ildiko, C Minori, K Manish, S AF Toshihiko, Doi Jaafar, Bennouna Lin, Shen Peter, Enzinger Wang Ruixue Ildiko, Csiki Minori, Koshiji Manish, Shah TI Pembrolizumab versus physician-choice chemotherapy for previously treated patients with advanced/metastatic squamous or adenocarcinoma of the esophagus or Siewert I adenocarcinoma of the esophagogastric junction (EGJ): Randomized, phase 3 KEYNOTE-18 SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 18th World Congress of the European-Society-for-Medical-Oncology (ESMO) on Gastrointestinal Cancer CY JUN 29-JUL 02, 2016 CL Barcelona, SPAIN SP European Soc Med Oncol C1 [Toshihiko, Doi] Natl Canc Ctr Hosp East, Kashiwa, Chiba, Japan. [Jaafar, Bennouna] Inst Cancerol Ouest, Nantes, France. [Lin, Shen] Peking Univ, Canc Hosp & Inst, Beijing, Peoples R China. [Peter, Enzinger] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wang Ruixue] MSD China, Beijing, Peoples R China. [Ildiko, Csiki; Minori, Koshiji] Merck & Co Inc, Kenilworth, NJ USA. [Manish, Shah] Weill Cornell Med Coll, New York, NY USA. [Manish, Shah] New York Presbyterian Hosp, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2016 VL 27 SU 2 MA P-280 BP 81 EP 81 PG 1 WC Oncology SC Oncology GA DR2TG UT WOS:000379756200271 ER PT J AU Andrew, Z Peter, G Masatoshi, K Richard, F Ling, Y Paolo, A Josep, L AF Andrew, Zhu Peter, Galle Masatoshi, Kudo Richard, Finn Ling, Yang Paolo, Abada Josep, Llovet TI A randomized, double-blind, placebo-controlled Phase III study of ramucirumab versus placebo as second-line treatment in patients with hepatocellular carcinoma and elevated baseline alpha-fetoprotein following first-line sorafenib (REACH-2) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 18th World Congress of the European-Society-for-Medical-Oncology (ESMO) on Gastrointestinal Cancer CY JUN 29-JUL 02, 2016 CL Barcelona, SPAIN SP European Soc Med Oncol C1 [Andrew, Zhu] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Peter, Galle] Univ Med Ctr Mainz, Mainz, Germany. [Masatoshi, Kudo] Kinki Univ, Sch Med, Osaka, Japan. [Richard, Finn] Univ Calif Los Angeles, Los Angeles, CA USA. [Ling, Yang] Eli Lilly & Co, Bridgewater, NJ USA. [Paolo, Abada] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Josep, Llovet] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2016 VL 27 SU 2 MA P-285 BP 83 EP 83 PG 1 WC Oncology SC Oncology GA DR2TG UT WOS:000379756200276 ER PT J AU Ryan, DP Murphy, J Mahalingam, D Strickler, J Stein, S Sirard, C Landau, S Bendell, J AF Ryan, D. P. Murphy, J. Mahalingam, D. Strickler, J. Stein, S. Sirard, C. Landau, S. Bendell, J. TI Current results of a phase I study of DKN-01 in combination with paclitaxel (P) in patients (pts) with advanced DKK1+esophageal cancer (EC) or gastro-esophageal junction tumors (GEJ) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 18th World Congress of the European-Society-for-Medical-Oncology (ESMO) on Gastrointestinal Cancer CY JUN 29-JUL 02, 2016 CL Barcelona, SPAIN SP European Soc Med Oncol C1 [Ryan, D. P.; Murphy, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mahalingam, D.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Strickler, J.] Duke Univ, Durham, NC USA. [Stein, S.] Yale Univ, Ctr Canc, New Haven, CT USA. [Sirard, C.] Leap Therapeut, Cambridge, MA USA. [Landau, S.] Hlth Care Ventures, Cambridge, MA USA. [Bendell, J.] Sarah Cannon Res Inst, Nashville, TN USA. [Bendell, J.] Tennessee Oncol, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2016 VL 27 SU 2 MA PD-016 BP 108 EP 108 PG 1 WC Oncology SC Oncology GA DR2TG UT WOS:000379756200359 ER PT J AU Tabernero, J Robert, JM Ohtsu, A Yoshino, T Garcia-Carbonero, R Pastorino, A Peeters, M Winkler, R Makris, L Wahba, M Zaniboni, A Shimada, Y Yamazaki, K Komatsu, Y Hochster, H Lenz, HJ Falcone, A Tran, B Van Cutsem, E AF Tabernero, J. Robert, J. Mayer Ohtsu, A. Yoshino, T. Garcia-Carbonero, R. Pastorino, A. Peeters, M. Winkler, R. Makris, L. Wahba, M. Zaniboni, A. Shimada, Y. Yamazaki, K. Komatsu, Y. Hochster, H. Lenz, H. -J. Falcone, A. Tran, B. Van Cutsem, E. TI RECOURSE trial: impact of adverse events on quality of life and duration of TAS-102 (trifluridine and tipiracil) treatment SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 18th World Congress of the European-Society-for-Medical-Oncology (ESMO) on Gastrointestinal Cancer CY JUN 29-JUL 02, 2016 CL Barcelona, SPAIN SP European Soc Med Oncol C1 [Tabernero, J.] Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, Barcelona, Spain. [Robert, J. Mayer] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ohtsu, A.; Yoshino, T.] Natl Canc Ctr Hosp East, Kashiwa, Chiba, Japan. [Garcia-Carbonero, R.] Hosp Univ 12 Octubre, Madrid, Spain. [Pastorino, A.] IRCCS AOU San Martino IST, Genoa, Italy. [Peeters, M.] Antwerp Univ Hosp, Edegem, Belgium. [Winkler, R.; Wahba, M.] Taiho Oncol Inc, Princeton, NJ USA. [Makris, L.] Stathmi Inc, New Hope, PA USA. [Zaniboni, A.] Fdn Poliambulanza, Brescia, Italy. [Shimada, Y.] Natl Canc Ctr, Chuo Ku, Tokyo, Japan. [Yamazaki, K.] Shizuoka Canc Ctr, Nagaizumi, Shizuoka, Japan. [Komatsu, Y.] Hokkaido Univ Hosp, Dept Canc Ctr, Sapporo, Hokkaido, Japan. [Hochster, H.] Yale Canc Ctr, New Haven, CT USA. [Lenz, H. -J.] USC Norris Comprehens Canc Ctr, Los Angeles, CA USA. [Falcone, A.] Azienda Osped Univ Pisana, Pisa, Italy. [Tran, B.] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Van Cutsem, E.] Univ Hosp Gasthuisberg, Leuven, Belgium. RI Peeters, Marc/C-5525-2013 OI Peeters, Marc/0000-0003-4969-2303 NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2016 VL 27 SU 2 MA PD-025 BP 111 EP 111 PG 1 WC Oncology SC Oncology GA DR2TG UT WOS:000379756200368 ER PT J AU Abrams, T Hess, L Zhu, Y Schelman, W Liepa, A Fuchs, C AF Abrams, T. Hess, L. Zhu, Y. Schelman, W. Liepa, A. Fuchs, C. TI Heterogeneity in the first-line treatment of patients with advanced or metastatic gastric cancer in the US SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 18th World Congress of the European-Society-for-Medical-Oncology (ESMO) on Gastrointestinal Cancer CY JUN 29-JUL 02, 2016 CL Barcelona, SPAIN SP European Soc Med Oncol C1 [Abrams, T.] Dana Farber Canc Inst, Boston, MA USA. [Hess, L.; Zhu, Y.; Schelman, W.; Liepa, A.] Eli Lilly & Co, Indianapolis, IN USA. [Fuchs, C.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2016 VL 27 SU 2 MA PD-034 BP 115 EP 115 PG 1 WC Oncology SC Oncology GA DR2TG UT WOS:000379756200377 ER PT J AU Strosberg, J Wolin, E Chasen, B Kulke, M Bushnell, D Chaplin, M Baum, R Kunz, P Hobday, T Oberg, K Sierra, ML Kwekkeboom, D Ruszniewski, P Krenning, E Hendifar, A AF Strosberg, J. Wolin, E. Chasen, B. Kulke, M. Bushnell, D. Chaplin, M. Baum, R. Kunz, P. Hobday, T. Oberg, K. Sierra, M. Lopera Kwekkeboom, D. Ruszniewski, P. Krenning, E. Hendifar, A. TI NETTER-1 phase III: efficacy and safety results in patients with midgut neuroendocrine tumors treated with 177Lu-dotatate SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 18th World Congress of the European-Society-for-Medical-Oncology (ESMO) on Gastrointestinal Cancer CY JUN 29-JUL 02, 2016 CL Barcelona, SPAIN SP European Soc Med Oncol C1 [Strosberg, J.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Wolin, E.] Cedars Sinai Med Ctr, Samuel Oschin Canc Ctr, Carcinoid Neuroendocrine Tumor Program, Los Angeles, CA 90048 USA. [Chasen, B.] Univ Kentucky, Markey Canc Ctr, Lexington, KY USA. [Kulke, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bushnell, D.] Univ Iowa, Iowa City, IA USA. [Chaplin, M.] Royal Free Hosp, London, England. [Baum, R.] Zent Klin Bad Berka, Bad Berka, Germany. [Kunz, P.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Hobday, T.] Mayo Clin, Coll Med, Rochester, MN USA. [Oberg, K.] Uppsala Univ, Univ Hosp, Uppsala, Sweden. [Sierra, M. Lopera] Adv Accelerator Applicat, New York, NY USA. [Kwekkeboom, D.] Erasmus MC, Rotterdam, Netherlands. [Ruszniewski, P.] Hop Beaujon, Clichy, France. [Krenning, E.] Erasmus MC, Rotterdam, Netherlands. [Hendifar, A.] Cedars Sinai Med Ctr, Samuel Oschin Canc Ctr, Los Angeles, CA 90048 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2016 VL 27 SU 2 MA O-009 BP 121 EP 121 PG 1 WC Oncology SC Oncology GA DR2TG UT WOS:000379756200392 ER PT J AU Tabernero, J van Geel, R Guren, T Yaeger, R Spreafico, A Faris, J Yoshino, T Yamada, Y Tae, WK Bendell, J Schuler, M Lenz, HJ Eskens, F Desai, J Hochster, H Avsar, E Demuth, T Sandor, V Elez, E Schellens, J AF Tabernero, J. van Geel, R. Guren, T. Yaeger, R. Spreafico, A. Faris, J. Yoshino, T. Yamada, Y. Tae, W. Kim Bendell, J. Schuler, M. Lenz, H. -J. Eskens, F. Desai, J. Hochster, H. Avsar, E. Demuth, T. Sandor, V. Elez, E. Schellens, J. TI Combination of encorafenib and cetuximab with or without alpelisib in patients with advanced BRAF-mutant colorectal cancer (BRAFm CRC): phase 2 results SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 18th World Congress of the European-Society-for-Medical-Oncology (ESMO) on Gastrointestinal Cancer CY JUN 29-JUL 02, 2016 CL Barcelona, SPAIN SP European Soc Med Oncol C1 [Tabernero, J.] Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, Barcelona, Spain. [van Geel, R.; Schellens, J.] Netherlands Canc Inst, Amsterdam, Netherlands. [Guren, T.] Oslo Univ Hosp, Oslo, Norway. [Yaeger, R.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Spreafico, A.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Faris, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yoshino, T.] Natl Canc Ctr Hosp East, Kashiwa, Chiba, Japan. [Yamada, Y.] Natl Canc Ctr, Chuo Ku, Tokyo, Japan. [Tae, W. Kim] Univ Ulsan, Coll Med, Asan Med Ctr, Ulsan, South Korea. [Bendell, J.] Sarah Cannon Res Inst, Nashville, TN USA. [Bendell, J.] Tennessee Oncol, Nashville, TN USA. [Schuler, M.] Univ Duisburg Essen, Univ Hosp Essen, West German Canc Ctr, Essen, Germany. [Lenz, H. -J.] USC Norris Comprehens Canc Ctr, Los Angeles, CA USA. [Eskens, F.] Erasmus MC Canc Inst, Rotterdam, Netherlands. [Desai, J.] Royal Melbourne Hosp, Parkville, Vic 3050, Australia. [Desai, J.] Peter MacCallum Canc Ctr, Walter & Eliza Hall Inst, Parkville, Vic, Australia. [Hochster, H.] Yale Canc Ctr, New Haven, CT USA. [Avsar, E.] Novartis Pharmaceut, E Hanover, NJ USA. [Demuth, T.] Novartis Pharma AG, Holzkirchen, Germany. [Sandor, V.] Array BioPharma Inc, Cambridge, MA USA. [Elez, E.] Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Barcelona, Spain. [Elez, E.] Univ Autonoma Barcelona, Inst Oncol VHIO, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2016 VL 27 SU 2 MA O-026 BP 127 EP 128 PG 2 WC Oncology SC Oncology GA DR2TG UT WOS:000379756200408 ER PT J AU Siddharthan, T North, CM Attia, EF Christiani, DC Checkley, W West, TE AF Siddharthan, Trishul North, Crystal M. Attia, Engi F. Christiani, David C. Checkley, William West, T. Eoin TI Global Health Education in Pulmonary and Critical Care Medicine Fellowships SO ANNALS OF THE AMERICAN THORACIC SOCIETY LA English DT Article AB A growing number of pulmonary and critical care medicine fellowship programs in the United States offer global health training opportunities. Formal, integrated global health programs within pulmonary and critical care fellowships are relatively new but are built on principles and ideals of global health that focus on the mutually beneficial exchange of knowledge and social justice. Although core competencies consistent with these overarching themes in global health education have not been formalized for pulmonary and critical care trainees, relevant competency areas include clinical knowledge, international research training, cultural competency, and clinical and research capacity building. Existing global health education in U.S. pulmonary and critical care medicine training programs can generally be classified as one of three different models: integrated global health tracks, global health electives, and additional research years. Successful global health education programs foster partnerships and collaborations with international sites that emphasize bidirectional exchange. This bidirectional exchange includes ongoing, equitable commitments to mutual opportunities for training and professional development, including a focus on the particular knowledge and skill sets critical for addressing the unique priorities of individual countries. However, barriers related to the availability of mentorship, funding, and dedicated time exist to expanding global health education in pulmonary and critical care medicine. The implementation of global health training within pulmonary and critical care medicine programs requires continued optimization, but this training is essential to prepare the next generation of physicians to address the global aspects of respiratory disease and critical illness. C1 [Siddharthan, Trishul; Checkley, William] Johns Hopkins Univ, Johns Hopkins Sch Med, Dept Pulm & Crit Care Med, Baltimore, MD USA. [Siddharthan, Trishul; North, Crystal M.] Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Program Global Dis Epidemiol & Control, Baltimore, MD USA. [North, Crystal M.; Christiani, David C.] NIH, Fogarty Int Ctr, Fogarty Global Hlth Fellowship, Bethesda, MD USA. [North, Crystal M.; Christiani, David C.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA USA. [Attia, Engi F.; West, T. Eoin] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Checkley, William] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA USA. [West, T. Eoin] Univ Washington, Dept Global Hlth, Seattle, WA USA. [West, T. Eoin] Univ Washington, Int Resp & Severe Illness Ctr, Seattle, WA USA. RP Siddharthan, T (reprint author), Dept Pulm & Crit Care Med, 1830 E Monument St,5th Floor, Baltimore, MD 21287 USA. EM tsiddha1@jhmi.edu OI Attia, Engi/0000-0002-5044-9602 FU Fogarty International Center [5R25TW009340, R25TW009337]; Harvard-National Institute of Environmental Health Sciences Center for Environmental Health [P30ES000002]; NHLBI/National Institutes of Health [K99HL096955]; Fogarty International Center/National Cancer Institute/National Institute of Environmental Health Sciences [U01TW010107] FX Supported by Fogarty International Center grants 5R25TW009340 and R25TW009337 (T.S., C.M.N.), the Harvard-National Institute of Environmental Health Sciences Center for Environmental Health grant P30ES000002 (C.M.N., D.C.C.), the NHLBI/National Institutes of Health grant K99HL096955 (W.C.), and Fogarty International Center/National Cancer Institute/National Institute of Environmental Health Sciences grant U01TW010107 (W.C.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the respective institutions or governmental organizations. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1546-3222 EI 2325-6621 J9 ANN AM THORAC SOC JI Ann. Am. Thoracic Society PD JUN PY 2016 VL 13 IS 6 BP 779 EP 783 DI 10.1513/AnnalsATS.201601-028PS PG 5 WC Respiratory System SC Respiratory System GA DR7WD UT WOS:000380109500009 PM 26974557 ER PT J AU Bull, CJ Bonilla, C Holly, JMP Perks, CM Davies, N Haycock, P Yu, OHY Richards, JB Eeles, R Easton, D Kote-Jarai, Z Al Olama, AA Benlloch, S Muir, K Giles, GG MacInnis, RJ Wiklund, F Gronberg, H Haiman, CA Schleutker, J Nordestgaard, BG Travis, RC Neal, D Pashayan, N Khaw, KT Stanford, JL Blot, WJ Thibodeau, S Maier, C Kibel, AS Cybulski, C Cannon-Albright, L Brenner, H Park, J Kaneva, R Batra, J Teixeira, MR Micheal, A Pandha, H Smith, GD Lewis, SJ Martin, RM AF Bull, Caroline J. Bonilla, Carolina Holly, Jeff M. P. Perks, Claire M. Davies, Neil Haycock, Philip Yu, Oriana Hoi Yun Richards, J. Brent Eeles, Rosalind Easton, Doug Kote-Jarai, Zsofia Al Olama, Ali Amin Benlloch, Sara Muir, Kenneth Giles, Graham G. MacInnis, Robert J. Wiklund, Fredrik Gronberg, Henrik Haiman, Christopher A. Schleutker, Johanna Nordestgaard, Borge G. Travis, Ruth C. Neal, David Pashayan, Nora Khaw, Kay-Tee Stanford, Janet L. Blot, William J. Thibodeau, Stephen Maier, Christiane Kibel, Adam S. Cybulski, Cezary Cannon-Albright, Lisa Brenner, Hermann Park, Jong Kaneva, Radka Batra, Jyotsna Teixeira, Manuel R. Micheal, Agnieszka Pandha, Hardev Smith, George Davey Lewis, Sarah J. Martin, Richard M. CA PRACTICAL Consortium TI Blood lipids and prostate cancer: a Mendelian randomization analysis SO CANCER MEDICINE LA English DT Article DE Cholesterol; Mendelian randomization; prostate cancer; statins ID CORONARY-ARTERY-DISEASE; GENETIC-VARIANTS; COMMON VARIANTS; RISK; CHOLESTEROL; STATINS; METAANALYSIS; PREVENTION; SCORES; COHORT AB Genetic risk scores were used as unconfounded instruments for specific lipid traits (Mendelian randomization) to assess whether circulating lipids causally influence prostate cancer risk. Data from 22,249 prostate cancer cases and 22,133 controls from 22 studies within the international PRACTICAL consortium were analyzed. Allele scores based on single nucleotide polymorphisms (SNPs) previously reported to be uniquely associated with each of low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels, were first validated in an independent dataset, and then entered into logistic regression models to estimate the presence (and direction) of any causal effect of each lipid trait on prostate cancer risk. There was weak evidence for an association between the LDL genetic score and cancer grade: the odds ratio (OR) per genetically instrumented standard deviation (SD) in LDL, comparing high- (>= 7 Gleason score) versus low-grade (< 7 Gleason score) cancers was 1.50 (95% CI: 0.92, 2.46; P = 0.11). A genetically instrumented SD increase in TGs was weakly associated with stage: the OR for advanced versus localized cancer per unit increase in genetic risk score was 1.68 (95% CI: 0.95, 3.00; P = 0.08). The rs12916-T variant in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) was inversely associated with prostate cancer (OR: 0.97; 95% CI: 0.94, 1.00; P = 0.03). In conclusion, circulating lipids, instrumented by our genetic risk scores, did not appear to alter prostate cancer risk. We found weak evidence that higher LDL and TG levels increase aggressive prostate cancer risk, and that a variant in HMGCR (that mimics the LDL lowering effect of statin drugs) reduces risk. However, inferences are limited by sample size and evidence of pleiotropy. C1 [Bull, Caroline J.; Bonilla, Carolina; Davies, Neil; Haycock, Philip; Smith, George Davey; Lewis, Sarah J.; Martin, Richard M.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England. [Bull, Caroline J.; Bonilla, Carolina; Davies, Neil; Haycock, Philip; Smith, George Davey; Lewis, Sarah J.] Univ Bristol, Univ Bristol Integrat Epidemiol Unit, MRC, Bristol, Avon, England. [Bull, Caroline J.; Bonilla, Carolina; Holly, Jeff M. P.; Perks, Claire M.; Davies, Neil; Haycock, Philip; Muir, Kenneth; Lewis, Sarah J.; Martin, Richard M.] Univ Bristol, Integrat Canc Epidemiol Programme, Bristol, Avon, England. [Bull, Caroline J.; Holly, Jeff M. P.; Perks, Claire M.] Univ Bristol, Sch Clin Sci North Bristol, IGFs & Metab Endocrinol Grp, Bristol BS10 5NB, Avon, England. [Yu, Oriana Hoi Yun; Richards, J. Brent] McGill Univ, Div Endocrinol Epidemiol Biostat & Occupat Hlth, Dept Med, Montreal, PQ, Canada. [Richards, J. Brent] Kings Coll London, Dept Twin Res, London SE1 7EH, England. [Eeles, Rosalind; Kote-Jarai, Zsofia] Inst Canc Res, Sutton SM2 5NG, Surrey, England. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, London SW3 6JJ, England. [Al Olama, Ali Amin; Benlloch, Sara] Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Lab, Ctr Canc Genet Epidemiol, Worts Causeway, Cambridge, England. [Muir, Kenneth] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England. [Muir, Kenneth] Univ Manchester, Inst Populat Hlth, Manchester M13 9PL, Lancs, England. [Giles, Graham G.; MacInnis, Robert J.] Canc Council Victoria, Canc Epidemiol Ctr, 615 St Kilda Rd, Melbourne, Vic, Australia. [Giles, Graham G.; MacInnis, Robert J.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic 3010, Australia. [Wiklund, Fredrik; Gronberg, Henrik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Schleutker, Johanna] Univ Turku, Dept Med Biochem & Genet, Turku, Finland. [Schleutker, Johanna] Turku Univ Hosp, Dept Med Genet, Tyks Microbiol & Genet, Turku, Finland. [Schleutker, Johanna] Univ Tampere, Inst Biomed Technol BioMediTech, Tampere, Finland. [Schleutker, Johanna] FimLab Labs, Tampere, Finland. [Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev Ringvej 75, DK-2730 Herlev, Denmark. [Travis, Ruth C.] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol, Oxford, England. [Neal, David; Pashayan, Nora] Univ Cambridge, Surg Oncol Urooncol S4, Addenbrookes Hosp, Box 279,Hills Rd, Cambridge, England. [Neal, David; Pashayan, Nora] Canc Res UK Cambridge Res Inst, Li Ka Shing Ctr, Cambridge, England. [Pashayan, Nora] UCL, Dept Appl Hlth Res, 1-19 Torrington Pl, London WC1E 7HB, England. [Khaw, Kay-Tee] Univ Cambridge, Cambridge Inst Publ Hlth, Forvie Site,Robinson Way, Cambridge CB2 0SR, England. [Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. [Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Blot, William J.] Int Epidemiol Inst, 1455 Res Blvd,Suite 550, Rockville, MD 20850 USA. [Thibodeau, Stephen] Mayo Clin, Rochester, MN USA. [Maier, Christiane] Univ Hosp, Dept Urol, Ulm, Germany. [Maier, Christiane] Univ Hosp, Inst Human Genet, Ulm, Germany. [Kibel, Adam S.] Brigham & Womens Hosp, Dana Farber Canc Inst, 45 Francis St ASB II 3, Boston, MA 02115 USA. [Kibel, Adam S.] Washington Univ, St Louis, MO USA. [Cybulski, Cezary] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland. [Cannon-Albright, Lisa] Univ Utah, Sch Med, Dept Med, Div Genet Epidemiol, Salt Lake City, UT USA. [Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Brenner, Hermann] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany. [Brenner, Hermann] Natl Ctr Tumor Dis NCT, Heidelberg, Germany. [Brenner, Hermann] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany. [Park, Jong] H Lee Moffitt Canc Ctr & Res Inst, Div Canc Prevent & Control, Magnolia Dr, Tampa, FL 12902 USA. [Kaneva, Radka] Med Univ Sofia, Mol Med Ctr, 2 Zdrave St, Sofia 1431, Bulgaria. [Kaneva, Radka] Med Univ Sofia, Dept Med Chem & Biochem, 2 Zdrave St, Sofia 1431, Bulgaria. [Batra, Jyotsna] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Australian Prostate Canc Res Ctr Qld, Brisbane, Qld, Australia. [Batra, Jyotsna] Queensland Univ Technol, Sch Biomed Sci, Brisbane, Qld, Australia. [Teixeira, Manuel R.] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal. [Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, Oporto, Portugal. [Micheal, Agnieszka; Pandha, Hardev] Univ Surrey, Surrey GU2 7XH, England. [Martin, Richard M.] Natl Inst Hlth Res, Bristol Nutr Biomed Res Unit, Bristol, Avon, England. RP Martin, RM (reprint author), Univ Bristol, Sch Social & Community Med, Bristol, Avon, England. EM richard.martin@bristol.ac.uk RI Davey Smith, George/A-7407-2013; Brenner, Hermann/B-4627-2017; OI Davey Smith, George/0000-0002-1407-8314; Brenner, Hermann/0000-0002-6129-1572; Bonilla, Carolina/0000-0002-9972-6383; Lewis, Sarah/0000-0003-4311-6890 FU Wellcome Trust [WT083431MA]; Cancer Research UK programme [C18281/A19169]; Medical Research Council; University of Bristol [MC_UU_12013/1-9]; National Institute for Health Research (NIHR); University Hospitals Bristol NHS Foundation Trust; University of Bristol; Canadian Institutes of Health Research; European Commission's Seventh Framework Programme [223175 (HEALTH-F2-2009-223175)]; Cancer Research UK Grants [C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, C16913/A6135]; National Institutes of Health (NIH) Cancer Post-Cancer GWAS initiative grant [1 U19 CA 148537-01]; NIHR FX C. J. B. is funded by the Wellcome Trust 4-year studentship WT083431MA. The Integrative Cancer Epidemiology Programme is supported by Cancer Research UK programme grant C18281/A19169. The MRC IEU is supported by the Medical Research Council and the University of Bristol (MC_UU_12013/1-9). The NIHR Bristol Nutrition Biomedical Research Unit is funded by the National Institute for Health Research (NIHR) and is a partnership between University Hospitals Bristol NHS Foundation Trust and the University of Bristol. The CRUK study and PRACTICAL consortium is supported by the Canadian Institutes of Health Research, European Commission's Seventh Framework Programme grant agreement no. 223175 (HEALTH-F2-2009-223175), Cancer Research UK Grants C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, and C16913/A6135. The National Institutes of Health (NIH) Cancer Post-Cancer GWAS initiative grant no. 1 U19 CA 148537-01 (the GAME-ON initiative) and NIHR support to the Biomedical Research Centre and The Institute of Cancer Research and Royal Marsden NHS Foundation Trust. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 37 TC 2 Z9 2 U1 3 U2 5 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2045-7634 J9 CANCER MED-US JI Cancer Med. PD JUN PY 2016 VL 5 IS 6 BP 1125 EP 1136 DI 10.1002/cam4.695 PG 12 WC Oncology SC Oncology GA DR6ZB UT WOS:000380048700019 PM 26992435 ER PT J AU Paoluzzi, L Hanniford, D Sokolova, E Osman, I Darvishian, F Wang, JH Bradner, JE Hernando, E AF Paoluzzi, Luca Hanniford, Douglas Sokolova, Elena Osman, Iman Darvishian, Farbod Wang, Jinhua Bradner, James E. Hernando, Eva TI BET and BRAF inhibitors act synergistically against BRAF-mutant melanoma SO CANCER MEDICINE LA English DT Article DE BET inhibition; BRAF inhibition; JQ1; Melanoma; Vemurafenib ID METASTATIC MELANOMA; SELECTIVE-INHIBITION; MEDIATED APOPTOSIS; CELL LYMPHOMA; EXPRESSION; TARGET; BRD4; STRESS; MODELS AB Despite major advances in the treatment of metastatic melanoma, treatment failure is still inevitable in most cases. Manipulation of key epigenetic regulators, including inhibition of Bromodomain and extra-terminal domain (BET) family members impairs cell proliferation in vitro and tumor growth in vivo in different cancers, including melanoma. Here, we investigated the effect of combining the BET inhibitor JQ1 with the BRAF inhibitor Vemurafenib in in vitro and in vivo models of BRAF-mutant melanoma. We performed cytotoxicity and apoptosis assays, and a xenograft mouse model to determine the in vitro and in vivo efficacy of JQ1 in combination with Vemurafenib against BRAF-mutant melanoma cell lines. Further, to investigate the molecular mechanisms underlying the effects of combined treatment, we conducted antibody arrays of in vitro drug-treated cell lines and RNA sequencing of drug-treated xenograft tumors. The combination of JQ1 and Vemurafenib acted synergistically in BRAF-mutant cell lines, resulting in marked apoptosis in vitro, with upregulation of proapoptotic proteins. In vivo, combination treatment suppressed tumor growth and significantly improved survival compared to either drug alone. RNA sequencing of tumor tissues revealed almost four thousand genes that were uniquely modulated by the combination, with several anti-apoptotic genes significantly down-regulated. Collectively, our data provide a rationale for combined BET and BRAF inhibition as a novel strategy for the treatment of melanoma. C1 [Paoluzzi, Luca; Wang, Jinhua] NYU, Langone Med Ctr, Inst Canc, 550 First Ave,SML 305, New York, NY 10016 USA. [Paoluzzi, Luca; Hanniford, Douglas; Sokolova, Elena; Osman, Iman; Hernando, Eva] NYU, Sch Med, Dept Pathol, New York, NY USA. [Paoluzzi, Luca; Hanniford, Douglas; Sokolova, Elena; Osman, Iman; Darvishian, Farbod; Wang, Jinhua; Hernando, Eva] NYU, Interdisciplinary Melanoma Cooperat Grp, Inst Canc, Langone Med Ctr, New York, NY USA. [Osman, Iman] NYU, Sch Med, Dept Dermatol, New York, NY USA. [Wang, Jinhua] NYU, Ctr Hlth Informat & Bioinformat, New York, NY USA. [Bradner, James E.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. RP Hernando, E (reprint author), NYU, Langone Med Ctr, Inst Canc, 550 First Ave,SML 305, New York, NY 10016 USA. EM eva.hernando@med.nyu.edu OI Hernando, Eva/0000-0003-1023-0312; Paoluzzi, Luca/0000-0002-2656-5224 FU Laura and Isaac Perlmutter Cancer Center [NIH/NCI P30CA016087]; National Institutes of Health S10 Grant [NIH/ORIP S10OD01058]; Pilot grant of the Melanoma Research Alliance FX The NYU Experimental Pathology Immunohistochemistry Core Laboratory and the Genomics Technology Center are supported in part by the Laura and Isaac Perlmutter Cancer Center Support Grant NIH/NCI P30CA016087" and the National Institutes of Health S10 Grant NIH/ORIP S10OD01058. This work was partially funded by a Pilot grant of the Melanoma Research Alliance. NR 33 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2045-7634 J9 CANCER MED-US JI Cancer Med. PD JUN PY 2016 VL 5 IS 6 BP 1183 EP 1193 DI 10.1002/cam4.667 PG 11 WC Oncology SC Oncology GA DR6ZB UT WOS:000380048700025 PM 27169980 ER PT J AU Shishehbor, MH Aronow, HD Bartholomew, JR Beckman, JA Froehlich, JB Lookstein, R Misra, S Roberts, AC Rosenfield, K Jaff, MR AF Shishehbor, Mehdi H. Aronow, Herbert D. Bartholomew, John R. Beckman, Joshua A. Froehlich, James B. Lookstein, Robert Misra, Sanjay Roberts, Anne C. Rosenfield, Kenneth Jaff, Michael R. TI Vascular Specialist Response to Medicare Evidence Development Coverage Advisory Committee (MEDCAC) Panel on Peripheral Artery Disease of the Lower Extremities SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material ID CRITICAL LIMB ISCHEMIA; NUTRITION EXAMINATION; COST-EFFECTIVENESS; NATIONAL-HEALTH; REVASCULARIZATION; MANAGEMENT; CLAUDICATION; AMPUTATION; EXERCISE; ANGIOPLASTY C1 [Shishehbor, Mehdi H.; Bartholomew, John R.] Cleveland Clin, Cleveland, OH 44195 USA. [Aronow, Herbert D.] Brown Univ, Providence, RI 02912 USA. [Beckman, Joshua A.] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA. [Froehlich, James B.] Univ Michigan, Ann Arbor, MI 48109 USA. [Lookstein, Robert] Mt Sinai, New York, NY USA. [Misra, Sanjay] Mayo Clin, Rochester, MN USA. [Roberts, Anne C.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Rosenfield, Kenneth; Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Shishehbor, MH (reprint author), Cleveland Clin, Inst Heart & Vasc, 9500 Euclid Ave,J3-5, Cleveland, OH 44195 USA. EM shishem@ccf.org OI Beckman, Joshua/0000-0001-8332-8439 NR 33 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 EI 1522-726X J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JUN PY 2016 VL 87 IS 7 BP 1181 EP 1186 DI 10.1002/ccd.26512 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DR6BC UT WOS:000379985100005 PM 27062192 ER PT J AU Plitt, A Ezekowitz, MD De Caterina, R Nordio, F Peterson, N Giugliano, RP AF Plitt, Anna Ezekowitz, Michael D. De Caterina, Raffaele Nordio, Francesco Peterson, Nancy Giugliano, Robert P. CA ENGAGE AF-TIMI 48 Investigators TI Cardioversion of Atrial Fibrillation in ENGAGE AF-TIMI 48 SO CLINICAL CARDIOLOGY LA English DT Article C1 [Plitt, Anna] Sinai Med Ctr, Dept Med, New York, NY USA. [Ezekowitz, Michael D.] Jefferson Med Coll, Dept Cardiovasc Med, Wynnewood, PA USA. [De Caterina, Raffaele] Univ G DAnnunzio, Inst Cardiol, Dept Cardiol, Chieti, Italy. Univ G DAnnunzio, Ctr Excellence Aging, Chieti, Italy. [Nordio, Francesco; Giugliano, Robert P.] Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. [Peterson, Nancy] Daiichi Sankyo Pharma Dev, Dept Clin Dev, Edison, NJ USA. RP Giugliano, RP (reprint author), TIMI Study Grp, 350 Longwood Ave,First Floor Off, Boston, MA 02115 USA. EM rgiugliano@partners.org RI De Caterina, Raffaele/K-3857-2016 OI De Caterina, Raffaele/0000-0003-1637-574X NR 4 TC 6 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 EI 1932-8737 J9 CLIN CARDIOL JI Clin. Cardiol. PD JUN PY 2016 VL 39 IS 6 BP 345 EP 346 DI 10.1002/clc.22537 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DR5DY UT WOS:000379924400005 PM 27028520 ER PT J AU Schulze-Spate, U Dietrich, T Wu, C Wang, K Hasturk, H Dibart, S AF Schulze-Spate, Ulrike Dietrich, Thomas Wu, Christina Wang, Kun Hasturk, Hatice Dibart, Serge TI Systemic vitamin D supplementation and local bone formation after maxillary sinus augmentation - a randomized, double-blind, placebo-controlled clinical investigation SO CLINICAL ORAL IMPLANTS RESEARCH LA English DT Article DE bone biology; bone graft; osteoclast; vitamin D ID BETA-TRICALCIUM PHOSPHATE; HISTOMORPHOMETRIC EVALUATION; OSTEOCLAST DIFFERENTIATION; AUTOGENOUS BONE; DENTAL IMPLANTS; IN-VIVO; DENSITY; CALCIUM; FLOOR; METABOLISM AB Objectives: Maxillary sinus augmentation procedures with bone replacement grafts aimed to increase bone height in the posterior maxilla. During healing, bone particles are partially resorbed and replaced by the patient's own bone. Vitamin D plays an essential role in calcium homeostasis and is critical for bone formation and remodeling. Materials and methods: This randomized, double-blind, placebo -controlled clinical investigation studied whether oral supplementation with vitamin D3 (5000 IU) combined with calcium (600 mg) impacts bone formation and remodeling after maxillary sinus augmentation compared to a placebo medication containing calcium alone (n = 10/group). Bone cores were harvested at the time of implant placement (6 8 months) for histological analysis. Results: Serum 25-hydroxyvitamin D (25-0HD) levels were comparable between both groups at the baseline (P nonsignificant [n.s.l). Vitamin D3 calcium supplementation improved significantly serum 25-OHD levels (placebo vs. vitamin D3+ group: 25-OHD ng/ml: 31.13 +/- 1 7.06 vs. 61.11 +/- 20.42, P <= 0.01); however, no statistically significant difference in bone formation or graft resorption was detected between groups. However, in the vitamin D3 group, a significant association was found between increased vitamin D levels and number of bone-resorbing osteoclasts around graft particles suggesting that local bone remodeling might be more pronounced when serum vitamin D levels were improved (r = 0.92, P <= 0.05). Conclusions: Vitamin D3+ calcium supplementation improves serum vitamin D levels and potentially impacts local bone remodeling on a cellular level. However, no statistically significant difference in bone formation or graft resorption was detected between groups. C1 [Schulze-Spate, Ulrike; Wang, Kun] Columbia Univ, Coll Dent Med, Div Periodont, Sect Oral & Diagnost Sci, New York, NY USA. [Dietrich, Thomas] Univ Birmingham, Dept Oral Surg, Sch Dent, Birmingham, W Midlands, England. [Wu, Christina] Columbia Univ, Dept Med, Div Cardiol, Med Ctr, New York, NY USA. [Hasturk, Hatice] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA USA. [Dibart, Serge] Boston Univ, Dept Periodontol, Goldman Sch Dent Med, Boston, MA 02215 USA. RP Schulze-Spate, U (reprint author), Columbia Univ, Coll Dent Med, 630 W 168th St,PH7E-200B, New York, NY 10032 USA. EM us2141@cumc.columbia.edu OI Dietrich, Thomas/0000-0002-2557-7645 NR 39 TC 3 Z9 3 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0905-7161 EI 1600-0501 J9 CLIN ORAL IMPLAN RES JI Clin. Oral Implant. Res. PD JUN PY 2016 VL 27 IS 6 BP 701 EP 706 DI 10.1111/clr.12641 PG 6 WC Dentistry, Oral Surgery & Medicine; Engineering, Biomedical SC Dentistry, Oral Surgery & Medicine; Engineering GA DR5BE UT WOS:000379917200011 PM 26178580 ER PT J AU Patel, MS Raza, SS Bhakta, A Ewing, T Bukur, M Vagefi, PA Salim, A Malinoski, DJ AF Patel, Madhukar S. Raza, Shariq S. Bhakta, Akash Ewing, Tyler Bukur, Marko Vagefi, Parsia A. Salim, Ali Malinoski, Darren J. TI Patients on state organ donor registries receive similar levels of intensive care compared to those who are not: an opportunity to increase public intent to donate SO CLINICAL TRANSPLANTATION LA English DT Article DE critical care; donor registration; end-of-life decisions; first-person authorization; organ donation ID MOTOR-VEHICLES; ETHNIC-GROUPS; REGISTRATION; CONSENT; KNOWLEDGE; ATTITUDES; EDUCATION; CLERKS; SIGN AB The intent to donate organs is affected by the public perception that patients on state registries receive less aggressive life-saving care in order to allow organ donation to proceed. However, the association between first person authorization to donate organs and the actual care received by eventual organ donors in hospitals is unknown. From August 2010 to April 2011, all eight organ procurement organizations in United Network for Organ Sharing Region 5 prospectively recorded demographic data and organ utilization rates on all donors after neurologic determination of death (DNDDs). Critical care and physiologic parameters were also recorded at referral for imminent neurologic death and prior to authorization for donation to reflect the aggressiveness of provided care. There were 586 DNDDs and 23% were on a state registry. Compared to non-registered DNDDs, those on state registries were older but were noted to have similar critical care parameters at both referral and authorization. Furthermore, there was no significant difference in organs procured per donor or organs transplanted per donor between registered and non-registered DNDDs. Thus, DNDDs who are on state donor registries receive similar levels of intensive care compared to non-registered donors. The association noted in this study may therefore help to dispel a common misperception that decreases the intent to donate. C1 [Patel, Madhukar S.; Raza, Shariq S.; Vagefi, Parsia A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Bhakta, Akash] Western Univ Hlth Sci, Pomona, CA USA. [Ewing, Tyler] Stanford Univ, Dept Anesthesiol, Stanford, CA 94305 USA. [Bukur, Marko] Broward Gen Med Ctr, Dept Trauma & Crit Care, Ft Lauderdale, FL USA. [Salim, Ali] Brigham & Womens Hosp, Div Trauma Burns & Surg Crit Care, 75 Francis St, Boston, MA 02115 USA. [Malinoski, Darren J.] Vet Affairs Portland Hlth Care Syst, Surg Crit Care Sect, Portland, OR USA. [Malinoski, Darren J.] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA. RP Malinoski, DJ (reprint author), Vet Affairs Portland Hlth Care Syst, POB 1034-P3ANES, Portland, OR 97207 USA. EM darren.malinoski@va.gov FU Health Resources and Services Administration [R38OT22183, 234-2005-37011C] FX The authors would like to thank all of the members of the UNOS Region 5 DMG workgroup as well as the donors, recipients, staff, and leadership of the eight OPOs in Region 5: Jennifer Treece (Donor Network of Arizona); Ricardo Elizondo (California Transplant Donor Network); Christopher Good and Tamra Grote (Golden State Donor Services); Scott Bunting and Alisa Suarez (OneLegacy); Jill Stinebring (Lifesharing); Ann Roberson (New Mexico Donor Services); Galyn Schoenstein (Nevada Donor Network); and Craig Myrick and Mike Ingraham (Intermountain Donor Services). This work was supported in part by Health Resources and Services Administration grant R38OT22183 and contract 234-2005-37011C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 19 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0902-0063 EI 1399-0012 J9 CLIN TRANSPLANT JI Clin. Transplant. PD JUN PY 2016 VL 30 IS 6 BP 682 EP 687 DI 10.1111/ctr.12734 PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA DR5PO UT WOS:000379955100005 PM 26992655 ER PT J AU Sinclair, CF Bumpous, JM Haugen, BR Chala, A Meltzer, D Miller, BS Tolley, NS Shin, JJ Woodson, G Randolph, GW AF Sinclair, Catherine F. Bumpous, Jeffrey M. Haugen, Bryan R. Chala, Andres Meltzer, Daniel Miller, Barbra S. Tolley, Neil S. Shin, Jennifer J. Woodson, Gayle Randolph, Gregory W. TI Laryngeal examination in thyroid and parathyroid surgery: An American Head and Neck Society consensus statement SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE thyroidectomy; voice; larynx; recurrent laryngeal nerve; vocal fold paralysis ID ASSESSOR-BLIND EVALUATION; VOCAL CORD EXAMINATION; RADIOLOGIC-DIAGNOSIS; SINGING VOICE; NERVE; FOLD; ULTRASOUND; ULTRASONOGRAPHY; CANCER; EXPERIENCE AB This American Head and Neck Society (AHNS) consensus statement discusses the techniques of laryngeal examination for patients undergoing thyroidectomy and parathyroidectomy. It is intended to help guide all clinicians who diagnose or manage adult patients with thyroid disease for whom surgery is indicated, contemplated, or has been performed. This consensus statement concludes that flexible transnasal laryngoscopy is the optimal laryngeal examination technique, with other techniques including laryngeal ultrasound and stroboscopy being useful in selected scenarios. (C) 2016 Wiley Periodicals, Inc. C1 [Sinclair, Catherine F.] Icahn Sch Med Mt Sinai, Dept Head & Neck Surg, New York, NY 10029 USA. [Bumpous, Jeffrey M.] Univ Louisville, Dept Otolaryngol, Louisville, KY 40292 USA. [Haugen, Bryan R.] Univ Colorado, Sch Med, Aurora, CO USA. [Chala, Andres] Univ Caldas, Manizales, Caldas, Colombia. [Meltzer, Daniel] Mt Sinai, New York, NY USA. [Miller, Barbra S.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Tolley, Neil S.] Imperial Coll London, Dept Surg, London, England. [Shin, Jennifer J.] Harvard, Boston, MA USA. [Woodson, Gayle] Southern Illinois Univ, Sch Med, Dept Otolaryngol, Carbondale, IL USA. [Randolph, Gregory W.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Sinclair, CF (reprint author), Mt Sinai St Lukes Roosevelt Hosp, Dept Head & Neck Surg Otolaryngol, 1111 Amsterdam Ave, New York, NY 10019 USA. EM casinclair@chpnet.org NR 46 TC 2 Z9 2 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1043-3074 EI 1097-0347 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD JUN PY 2016 VL 38 IS 6 BP 811 EP 819 DI 10.1002/hed.24409 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA DR5JS UT WOS:000379939900005 PM 26970554 ER PT J AU Mormino, EC Papp, KV AF Mormino, Elizabeth C. Papp, Kathryn V. TI Cognitive Decline in Preclinical Stage 2 Alzheimer Disease and Implications for Prevention Trials SO JAMA NEUROLOGY LA English DT Editorial Material ID LONGITUDINAL COHORT; NEURODEGENERATION C1 [Mormino, Elizabeth C.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. [Papp, Kathryn V.] Harvard Med Sch, Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, Boston, MA USA. RP Mormino, EC (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, 149 13th St, Charlestown, MA 02129 USA. EM bmormino@nmr.mgh.harvard.edu NR 14 TC 1 Z9 1 U1 4 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD JUN PY 2016 VL 73 IS 6 BP 640 EP 642 DI 10.1001/jamaneurol.2016.0281 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA DQ7WL UT WOS:000379418600011 PM 27064971 ER PT J AU Yokoyama, JS Wang, YP Schork, AJ Thompson, WK Karch, CM Cruchaga, C McEvoy, LK Witoelar, A Chen, CH Holland, D Brewer, JB Franke, A Dillon, WP Wilson, DM Mukherjee, P Hess, CP Miller, Z Bonham, LW Shen, J Rabinovici, GD Rosen, HJ Miller, BL Hyman, BT Schellenberg, GD Karlsen, TH Andreassen, OA Dale, AM Desikan, RS AF Yokoyama, Jennifer S. Wang, Yunpeng Schork, Andrew J. Thompson, Wesley K. Karch, Celeste M. Cruchaga, Carlos McEvoy, Linda K. Witoelar, Aree Chen, Chi-Hua Holland, Dominic Brewer, James B. Franke, Andre Dillon, William P. Wilson, David M. Mukherjee, Pratik Hess, Christopher P. Miller, Zachary Bonham, Luke W. Shen, Jeffrey Rabinovici, Gil D. Rosen, Howard J. Miller, Bruce L. Hyman, Bradley T. Schellenberg, Gerard D. Karlsen, Tom H. Andreassen, Ole A. Dale, Anders M. Desikan, Rahul S. CA Alzheimer's Dis Neuroimaging Initi TI Association Between Genetic Traits for Immune-Mediated Diseases and Alzheimer Disease SO JAMA NEUROLOGY LA English DT Article ID INOSITOL POLYPHOSPHATE MULTIKINASE; GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; COMMON VARIANTS; IDENTIFIES 7; RISK LOCI; METAANALYSIS; INFLAMMATION; COACTIVATOR; PLEIOTROPY AB IMPORTANCE Late-onset Alzheimer disease (AD), the most common form of dementia, places a large burden on families and society. Although epidemiological and clinical evidence suggests a relationship between inflammation and AD, their relationship is not well understood and could have implications for treatment and prevention strategies. OBJECTIVE To determine whether a subset of genes involved with increased risk of inflammation are also associated with increased risk for AD. DESIGN, SETTING, AND PARTICIPANTS In a genetic epidemiology study conducted in July 2015, we systematically investigated genetic overlap between AD (International Genomics of Alzheimer's Project stage 1) and Crohn disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, and psoriasis using summary data from genome-wide association studies at multiple academic clinical research centers. P values and odds ratios from genome-wide association studies of more than 100 000 individuals were from previous comparisons of patients vs respective control cohorts. Diagnosis for each disorder was previously established for the parent study using consensus criteria. MAIN OUTCOMES AND MEASURES The primary outcomewas the pleiotropic (conjunction) false discovery rate P value. Follow-up for candidate variants included neuritic plaque and neurofibrillary tangle pathology; longitudinal Alzheimer's Disease Assessment Scale cognitive subscale scores as a measure of cognitive dysfunction (Alzheimer's Disease Neuroimaging Initiative); and gene expression in AD vs control brains (Gene Expression Omnibus data). RESULTS Eight single-nucleotide polymorphisms (false discovery rate P < .05) were associated with both AD and immune-mediated diseases. Of these, rs2516049 (closest gene HLA-DRB5; conjunction false discovery rate P = .04 for AD and psoriasis, 5.37 x 10(-5) for AD, and 6.03 x 10(-15) for psoriasis) and rs12570088 (closest gene IPMK; conjunction false discovery rate P = .009 for AD and Crohn disease, P = 5.73 x 10(-6) for AD, and 6.57 x 10(-5) for Crohn disease) demonstrated the same direction of allelic effect between AD and the immune-mediated diseases. Both rs2516049 and rs12570088 were significantly associated with neurofibrillary tangle pathology (P = .01352 and.03151, respectively); rs2516049 additionally correlated with longitudinal decline on Alzheimer's Disease Assessment Scale cognitive subscale scores (beta [SE], 0.405 [0.190]; P = .03). Regarding gene expression, HLA-DRA and IPMK transcript expression was significantly altered in AD brains compared with control brains (HLA-DRA: beta [SE], 0.155 [0.024]; P = 1.97 x 10(-10); IPMK: beta [SE], -0.096 [0.013]; P = 7.57 x 10(-13)). CONCLUSIONS AND RELEVANCE Our findings demonstrate genetic overlap between AD and immune-mediated diseases and suggest that immune system processes influence AD pathogenesis and progression. C1 [Yokoyama, Jennifer S.; Miller, Zachary; Bonham, Luke W.; Shen, Jeffrey; Rabinovici, Gil D.; Rosen, Howard J.; Miller, Bruce L.] Univ Calif San Francisco, Dept Neurol, 675 Nelson Rising Ln,Ste 190, San Francisco, CA 94158 USA. [Wang, Yunpeng; Karch, Celeste M.; Cruchaga, Carlos] Washington Univ, Dept Psychiat, St Louis, MO USA. [Wang, Yunpeng; Holland, Dominic; Brewer, James B.; Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Schork, Andrew J.; Dale, Anders M.] Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA. [Thompson, Wesley K.; Dale, Anders M.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [McEvoy, Linda K.; Chen, Chi-Hua; Brewer, James B.; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Witoelar, Aree; Andreassen, Ole A.] Univ Oslo, Inst Clin Med, Norwegian Ctr Mental Disorders Res, Oslo, Norway. [Witoelar, Aree; Andreassen, Ole A.] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway. [Franke, Andre] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany. [Dillon, William P.; Wilson, David M.; Mukherjee, Pratik; Hess, Christopher P.; Desikan, Rahul S.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, Neuroradiol Sect, San Francisco, CA 94143 USA. [Hyman, Bradley T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Schellenberg, Gerard D.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA. [Karlsen, Tom H.] Oslo Univ Hosp, Rikshosp, Div Canc Med Surg & Transplantat, Internal Med Res Inst,Norwegian PSC Res Ctr, Oslo, Norway. [Karlsen, Tom H.] Oslo Univ Hosp, Rikshosp, Div Canc Med Surg & Transplantat, Internal Med Res Inst,KG Jebsen Inflammat Res Ctr, Oslo, Norway. [Karlsen, Tom H.] Univ Bergen, Inst Med, Div Gastroenterol, Bergen, Norway. RP Yokoyama, JS (reprint author), Univ Calif San Francisco, Dept Neurol, 675 Nelson Rising Ln,Ste 190, San Francisco, CA 94158 USA. EM jennifer.yokoyama@ucsf.edu RI Franke, Andre/B-2151-2010 OI Franke, Andre/0000-0003-1530-5811 FU National Institute on Aging [U24 AG21886, U01 AG016976, K01 AG049152, U01AG032984, RC2AG036528, U24-AG041689-01]; National Institutes of Health [AG046374, R01-AG045611, P50-AG023501, RC2DA029475, R01HD061414]; Research Council of Norway, European Union Joint Programme-Neurodegenerative Research [213837, 225989, 223273, 237250]; South-Eastern Norway Health Authority [2013-123]; Norwegian Health Associatio; KG Jebsen Foundation; John Douglas French Alzheimer's Foundation; Susan Marcus Memorial Fund Clinical Research Grant from the Association for Frontotemporal Degeneration; Larry L. Hillblom Foundation [2012-A-015-FEL]; Robert J. Glushko and Pamela Samuelson Foundation FX Data included in this study were obtained from the National Cell Repository for Alzheimer's Disease (supported by grant U24 AG21886 from the National Institute on Aging) and the National Alzheimer's Coordinating Center (supported by grant U01 AG016976 from the National Institute on Aging). This work was supported by grants AG046374 (Dr Andreassen), R01-AG045611 (Dr Rabinovici), P50-AG023501 (Drs B. L. Miller, Rosen, and Rabinovici), RC2DA029475 (Mr Schork), and R01HD061414 (Mr Schork) from the National Institutes of Health; grants 213837, 225989, 223273, and 237250 from the Research Council of Norway, European Union Joint Programme-Neurodegenerative Research (Dr Andreassen); grant 2013-123 from the South-Eastern Norway Health Authority (Dr Andreassen); the Norwegian Health Association (Dr Andreassen); the KG Jebsen Foundation (Dr Andreassen); the John Douglas French Alzheimer's Foundation (Drs B. L. Miller and Rabinovici); grant K01 AG049152 from the National Institute on Aging (Dr Yokoyama); a Susan Marcus Memorial Fund Clinical Research Grant from the Association for Frontotemporal Degeneration (Dr Yokoyama); grant 2012-A-015-FEL from the Larry L. Hillblom Foundation (Dr Yokoyama); and a graduate fellowship from the Robert J. Glushko and Pamela Samuelson Foundation (Mr Schork). The Alzheimer's Disease Genetics Consortium supported the collection of samples used in this study through grants U01AG032984 and RC2AG036528 from the National Institute on Aging (Dr Schellenberg). Data for this study were prepared, archived, and distributed by the National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site at the University of Pennsylvania, supported by grant U24-AG041689-01 from the National Institute on Aging (Dr Schellenberg). The International Genomics of Alzheimer's Disease Project funding sources are described in eAppendix 2 in the Supplement. NR 31 TC 10 Z9 10 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD JUN PY 2016 VL 73 IS 6 BP 691 EP 697 DI 10.1001/jamaneurol.2016.0150 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA DQ7WL UT WOS:000379418600019 PM 27088644 ER PT J AU Banducci, AN Bujarski, SJ Bonn-Miller, MO Patel, A Connolly, KM AF Banducci, Anne N. Bujarski, Sarah J. Bonn-Miller, Marcel O. Patel, Amee Connolly, Kevin M. TI The impact of intolerance of emotional distress and uncertainty on veterans with co-occurring PTSD and substance use disorders SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Distress tolerance; PTSD; Substance use disorders; Intolerance of uncertainty; Veterans ID POSTTRAUMATIC-STRESS-DISORDER; ANXIETY SENSITIVITY; CANNABIS USE; SYMPTOM SEVERITY; SERVICE MEMBERS; TOLERANCE; SCALE; IRAQ; INDIVIDUALS; AFGHANISTAN AB The risk of developing a substance use disorder (SUD) is significantly higher among veterans with post traumatic stress disorder (PTSD). Veterans with this co-occurrence have poorer outcomes than singly diagnosed veterans, which may be related to two risk factors: intolerance uncertainty (IU) and low tolerance of emotional distress (TED). We hypothesized low TED and high IU would independently and interactively relate to heightened PTSD symptomatology and trauma-cue elicited SUD cravings. A sample of 70 veterans (M age = 50; 95% men; 65% Black) with co-occurring PTSD-SUD was recruited. The Posttraumatic Stress Disorder Checklist (PCL), Craving Questionnaire, Distress Tolerance Scale, and Intolerance of Uncertainty Scale were administered. In general, low TED and high IU were significantly correlated with the PCL total and subscale scores. When examined within regression models, low TED was associated with elevated PCL scores and trauma-cue elicited SUD cravings; IU was not. However, there was a significant interaction between IU and TED; veterans with elevated IU and low TED had higher PCL Total, Hyperarousal, and Intrusions scores. This highlights the importance of assessing TED and IU among veterans with co-occurring PTSD-SUD, as these risk factors may not only be prognostic indicators of outcomes, but also treatment targets. Published by Elsevier Ltd. C1 [Banducci, Anne N.; Bujarski, Sarah J.; Patel, Amee; Connolly, Kevin M.] GV Sonny Montgomery Vet Affairs Med Ctr, 1500 E Woodrow Wilson Ave, Jackson, MS 39216 USA. [Banducci, Anne N.; Bujarski, Sarah J.; Patel, Amee; Connolly, Kevin M.] Univ Mississippi, Med Ctr, 2500N State St, Jackson, MS 39216 USA. [Banducci, Anne N.; Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, 795 Willow Rd 152-MPD, Menlo Pk, CA 94025 USA. [Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, 795 Willow Rd 152-MPD, Menlo Pk, CA 94025 USA. [Bonn-Miller, Marcel O.] Philadelphia VA Med Ctr, Ctr Excellence Substance Abuse Treatment & Educ, 3900 Woodland Ave, Philadelphia, PA 19104 USA. [Bonn-Miller, Marcel O.] Univ Penn, Dept Psychiat, Perelman Sch Med, 3440 Market St,Suite 370, Philadelphia, PA 19104 USA. RP Banducci, AN (reprint author), VA Palo Alto Hlth Care Syst, 795 Willow Rd 152-MPD, Menlo Pk, CA 94025 USA. EM anne.banducci@va.gov OI Banducci, Anne N/0000-0003-1213-7998 NR 59 TC 5 Z9 5 U1 6 U2 6 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 JUN PY 2016 VL 41 BP 73 EP 81 DI 10.1016/j.janxdis.2016.03.003 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DR7JS UT WOS:000380076500009 PM 27004450 ER PT J AU Rietman, EA Platig, J Tuszynski, JA Klement, GL AF Rietman, Edward A. Platig, John Tuszynski, Jack A. Klement, Giannoula Lakka TI Thermodynamic measures of cancer: Gibbs free energy and entropy of protein-protein interactions SO JOURNAL OF BIOLOGICAL PHYSICS LA English DT Article DE Cancer; Signaling networks; Gibbs free energy; Entropy; Protein-protein interactions; 5-year survival ID COMPREHENSIVE GENOMIC CHARACTERIZATION; INTERACTION NETWORKS; PATIENT SURVIVABILITY; ROBUSTNESS; COMPLEXITY; DRAFT; LAWS AB Thermodynamics is an important driving factor for chemical processes and for life. Earlier work has shown that each cancer has its own molecular signaling network that supports its life cycle and that different cancers have different thermodynamic entropies characterizing their signaling networks. The respective thermodynamic entropies correlate with 5-year survival for each cancer. We now show that by overlaying mRNA transcription data from a specific tumor type onto a human protein-protein interaction network, we can derive the Gibbs free energy for the specific cancer. The Gibbs free energy correlates with 5-year survival (Pearson correlation of -0.7181, p value of 0.0294). Using an expression relating entropy and Gibbs free energy to enthalpy, we derive an empirical relation for cancer network enthalpy. Combining this with previously published results, we now show a complete set of extensive thermodynamic properties and cancer type with 5-year survival. C1 [Rietman, Edward A.] Univ Massachusetts, Informat & Comp Sci Dept, Amherst, MA 01003 USA. [Platig, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Platig, John] Harvard Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Tuszynski, Jack A.] Univ Alberta, Dept Oncol, Fac Med & Dent, Edmonton, AB T6G 1Z2, Canada. [Tuszynski, Jack A.] Univ Alberta, Dept Phys, Edmonton, AB T6G 2E1, Canada. [Klement, Giannoula Lakka] Tufts Med Ctr, Floating Hosp Children, Pediat Hematol Oncol, Boston, MA 02111 USA. [Klement, Giannoula Lakka] Tufts Univ, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA. [Klement, Giannoula Lakka] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. RP Tuszynski, JA (reprint author), Univ Alberta, Dept Oncol, Fac Med & Dent, Edmonton, AB T6G 1Z2, Canada.; Tuszynski, JA (reprint author), Univ Alberta, Dept Phys, Edmonton, AB T6G 2E1, Canada. EM jtus@phys.ualberta.ca; glakkaklement@tuftsmedicalcenter.org FU Newman Lakka Cancer Foundation; CSTS Healthcare; NSERC; Canadian Breast Cancer Foundation; Allard Foundation; NIH NIGMS [RO1 GM93050]; Campanelli Foundation; Jack in the Beanstalk Foundation; Binational Science Foundation FX EAR was partly funded by the Newman Lakka Cancer Foundation, and CSTS Healthcare. JAT acknowledges funding from NSERC, Canadian Breast Cancer Foundation and the Allard Foundation. GLK was funded by NIH NIGMS RO1 GM93050, and philanthropic funds from Newman Lakka Cancer Foundation, Campanelli Foundation, Jack in the Beanstalk Foundation, and Binational Science Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Heath. NR 41 TC 3 Z9 3 U1 4 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0092-0606 EI 1573-0689 J9 J BIOL PHYS JI J. Biol. Phys. PD JUN PY 2016 VL 42 IS 3 BP 339 EP 350 DI 10.1007/s10867-016-9410-y PG 12 WC Biophysics SC Biophysics GA DR5DF UT WOS:000379922500003 PM 27012959 ER PT J AU Farmer, GW Blosnich, JR Jabson, JM Matthews, DD AF Farmer, Grant W. Blosnich, John R. Jabson, Jennifer M. Matthews, Derrick D. TI Gay Acres: Sexual Orientation Differences in Health Indicators Among Rural and Nonrural Individuals SO JOURNAL OF RURAL HEALTH LA English DT Article DE bisexuality; health disparities; homosexuality; rural health; sexual orientation ID BREAST-CANCER RISK; SUBSTANCE USE; MINORITY WOMEN; MENTAL-HEALTH; UNITED-STATES; BISEXUAL POPULATIONS; SOUTHERN LESBIANS; URBAN DIFFERENCES; CARE UTILIZATION; US STATES AB PurposeGeographic location is a significant factor that influences health status and health disparities. Yet, little is known about the relationship between geographic location and health and health disparities among lesbian, gay, and bisexual (LGB) persons. This study used a US population-based sample to evaluate the associations of sexual orientation with health indicators by rural/nonrural residence. MethodsData were pooled from the 10 states that collected sexual orientation in the 2010 Behavioral Risk Factor Surveillance System surveys. Rural status was defined using metropolitan statistical area, and group differences by sexual orientation were stratified by gender and rural/nonrural status. Chi-square tests for categorical variables were used to assess bivariate relationships. Multivariable logistic regression models stratified by gender and rural/nonrural status were used to assess the association of sexual orientation to health indicators, while adjusting for age, race/ethnicity, education, and partnership status. All analyses were weighted to adjust for the complex sampling design. FindingsSignificant differences between LGB and heterosexual participants emerged for several health indicators, with bisexuals having a greater number of differences than gay men/lesbians. There were fewer differences in health indicators for rural LGB participants compared to heterosexuals than nonrural participants. ConclusionsRural residence appears to influence the pattern of LGB health disparities. Future work is needed to confirm and identify the exact etiology or rural/nonrural differences in LGB health. C1 [Farmer, Grant W.] Washington Univ, Dept Surg, Div Publ Hlth Sci, St Louis, MO USA. [Blosnich, John R.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Blosnich, John R.; Matthews, Derrick D.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA USA. [Jabson, Jennifer M.] Univ Tennessee, Coll Educ Hlth & Human Sci, Dept Publ Hlth, Knoxville, TN USA. RP Blosnich, JR (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Univ Dr C,151C-U,Bldg 30, Pittsburgh, PA 15240 USA. EM John.blosnich@va.gov OI Matthews, Derrick/0000-0002-3579-3608 FU National Cancer Institute [5U54CA155496]; National Institute of Mental Health [T32MH094174]; National Institute on Minority Health and Health Disparities [L60 MD009167]; Department of Veterans Affairs Office of Academic Affiliations [TPP 72-013] FX This research was supported in part by the National Cancer Institute (grant 5U54CA155496), the National Institute of Mental Health (grant T32MH094174), National Institute on Minority Health and Health Disparities (grant L60 MD009167), and a postdoctoral fellowship through the Department of Veterans Affairs Office of Academic Affiliations (TPP 72-013). NR 55 TC 0 Z9 0 U1 3 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0890-765X EI 1748-0361 J9 J RURAL HEALTH JI J. Rural Health PD SUM PY 2016 VL 32 IS 3 BP 321 EP 331 DI 10.1111/jrh.12161 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DR3FX UT WOS:000379789100011 PM 26625172 ER PT J AU Garcia, JA Benboujja, F Beaudette, K Guo, R Boudoux, C Hartnick, CJ AF Garcia, Jordan A. Benboujja, Fouzi Beaudette, Kathy Guo, Rong Boudoux, Caroline Hartnick, Christopher J. TI Using Attenuation Coefficients From Optical Coherence Tomography as Markers of Vocal Fold Maturation SO LARYNGOSCOPE LA English DT Article DE Voice; dysphonia; airway; pediatric ID LAMINA PROPRIA; IN-VIVO; COLLAGEN; TECHNOLOGY; CATHETER; VERSICAN; BENIGN; BIOPSY; AGE AB Objectives/Hypothesis: Optical coherence tomography (OCT) is a promising technology to noninvasively assess vocal fold microanatomy. The goal of this study was to develop a methodology using OCT to identify quantifiable markers of vocal fold development. Study Design: In vivo study. Methods: A two-step process was developed to reproducibly image the midmembranous vocal fold edge of 10 patients younger than 2 years and 10 patients between 11 and 16 years of age using OCT. An image analysis algorithm was implemented to extract OCT-derived A-lines for each patient. These A-lines were divided into three zones according to apparent changes in slope. Relative attenuation coefficients, or tissue-and system-dependent parameters that describe the rate at which optical signal decays, were calculated for each zone. Results: Young patients had distinct relative attenuation coefficients in zone 1 (P < .0001), whereas zones 2 and 3 were indistinct (P = .1129). Older patients had distinct relative attenuation coefficients in zones 1, 2, and 3 (P < .0370). Between age groups, relative attenuation coefficients were different in zones 2 and 3 (P < .0001, P = .0315, respectively) and indistinct in zone 1 (P = .1438). Conclusions: Relative attenuation coefficients can be used as markers of vocal fold development. Differences in relative attenuation coefficients likely represent changes in extracellular matrix structure within the lamina propria and may become useful for guiding treatment of voice disorders in the pediatric population. C1 [Garcia, Jordan A.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA USA. [Benboujja, Fouzi; Beaudette, Kathy; Boudoux, Caroline] Polytech Montreal, Dept Engn Phys, Montreal, PQ, Canada. [Guo, Rong; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM christopher_hartnick@meei.harvard.edu FU Scholars in Medicine Office at Harvard Medical School; Massachusetts Eye and Ear Infirmary FX The lead author of this study was funded in part by the Scholars in Medicine Office at Harvard Medical School. Internal departmental funds at the Massachusetts Eye and Ear Infirmary covered the remaining costs of the study. NR 34 TC 1 Z9 1 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD JUN PY 2016 VL 126 IS 6 BP E218 EP E223 DI 10.1002/lary.25765 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA DR5ZF UT WOS:000379980200002 PM 26525926 ER PT J AU Axon, RN Gebregziabher, M Hunt, KJ Lynch, CP Payne, E Walker, RJ Egede, LE AF Axon, Robert Neal Gebregziabher, Mulugeta Hunt, Kelly J. Lynch, Cheryl P. Payne, Elizabeth Walker, Rebekah J. Egede, Leonard E. TI Comorbid depression is differentially associated with longitudinal medication nonadherence by race/ethnicity in patients with type 2 diabetes SO MEDICINE LA English DT Article DE depression; diabetes; medication adherence; race; ethnicity ID RANDOMIZED CONTROLLED-TRIAL; CORONARY-HEART-DISEASE; QUALITY-OF-LIFE; GLYCEMIC CONTROL; ADHERENCE; MELLITUS; VETERANS; THERAPY; CARE; INTERVENTIONS AB The aim of the study was to examine whether depression impacts medication nonadherence (MNA) over time and determine if race has a differential impact on MNA in patients with type 2 diabetes and comorbid depression.Generalized estimating equations were used with a longitudinal national cohort of 740,197 veterans with type 2 diabetes. MNA was the main outcome defined by <80% medication possession ratio for diabetes medications. The primary independent variable was comorbid depression. Analyses were adjusted for the longitudinal nature of the data and covariates including age, sex, marital status, and rural/urban residence.In adjusted models, MNA was higher in non-Hispanic blacks (NHBs) (odds ratio [OR] 1.58 [95% confidence intervalCI: 1.57, 1.59]), Hispanics (OR 1.34 [95% CI: 1.32, 1.35]), and the other/missing racial/ethnic group (OR 1.37 [95% CI: 1.36, 1.38]) than in non-Hispanic whites (NHWs). In stratified analyses, the odds of MNA associated with depression were highest in NHWs (OR 1.14 [95% CI: 1.12, 1.15]) and were significantly associated in the other 3 minority racial/ethnic groups. MNA was lower in rural than urban NHWs (OR 0.91 [95% CI: 0.90, 0.92]), NHBs (OR 0.92 [95% CI: 0.91, 0.94]), and the other/unknown racial/ethnic group (OR 0.89 [95% CI: 0.88, 0.90]), but higher in rural Hispanic patients (OR 1.12 [95% CI: 1.09, 1.14]).Depression was associated with increased odds of MNA in NHWs, as well as in minority groups, although associations were weaker in minority groups, perhaps as a result of the high baseline levels of MNA in minority groups. There were also differences by race/ethnicity in MNA in rural versus urban subjects. C1 [Axon, Robert Neal; Gebregziabher, Mulugeta; Hunt, Kelly J.; Lynch, Cheryl P.; Payne, Elizabeth; Walker, Rebekah J.; Egede, Leonard E.] Ralph H Johnson Dept Vet Affairs Med Ctr, Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC USA. [Gebregziabher, Mulugeta; Hunt, Kelly J.; Payne, Elizabeth] Med Univ South Carolina, Dept Publ Hlth, Charleston, SC USA. [Lynch, Cheryl P.; Walker, Rebekah J.; Egede, Leonard E.] Med Univ South Carolina, Div Gen Internal Med, Ctr Hlth Dispar Res, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ South Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,MSC 593, Charleston, SC 29425 USA. EM egedel@musc.edu OI Gebregziabher, Mulugeta/0000-0002-4826-481X FU VHA Health Services Research and Development (HSRD) program [IIR-06-219] FX This study was supported by grant #IIR-06-219 funded by the VHA Health Services Research and Development (HSR&D) program. The funding agency did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The manuscript represents the views of the authors and not those of the VA or HSR&D. Drs LEE and MG are the guarantor's of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 40 TC 0 Z9 0 U1 5 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7974 EI 1536-5964 J9 MEDICINE JI Medicine (Baltimore) PD JUN PY 2016 VL 95 IS 25 AR e3983 DI 10.1097/MD.0000000000003983 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA DR1JH UT WOS:000379661300043 PM 27336900 ER PT J AU Kieran, MW Goumnerova, L Manley, P Chi, SN Marcus, K Manzanera, AG Aguilar-Cordova, E DiPatri, AJ Tomita, T Lulla, R Aguilar, LK Goldman, S AF Kieran, Mark W. Goumnerova, Liliana Manley, Peter Chi, Susan N. Marcus, Karen Manzanera, Andrea G. Aguilar-Cordova, Estuardo DiPatri, Arthur J. Tomita, Tadanori Lulla, Rishi Aguilar, Laura K. Goldman, Stewart TI PHASE I STUDY OF GENE MEDIATED CYTOTOXIC IMMUNOTHERAPY WITH AdV-tk AS ADJUVANT TO SURGERY AND RADIATION THERAPY FOR PEDIATRIC MALIGNANT GLIOMA AND RECURRENT EPENDYMOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Kieran, Mark W.; Goumnerova, Liliana; Manley, Peter; Chi, Susan N.; Marcus, Karen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kieran, Mark W.; Goumnerova, Liliana; Manley, Peter; Chi, Susan N.; Marcus, Karen; Aguilar, Laura K.] Boston Childrens Hosp, Boston, MA USA. [Manzanera, Andrea G.; Aguilar-Cordova, Estuardo; Aguilar, Laura K.] Advantagene Inc, Auburndale, MA USA. [DiPatri, Arthur J.; Tomita, Tadanori; Lulla, Rishi; Goldman, Stewart] Lurie Childrens Hosp, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA EPT-14 BP 26 EP 27 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000103 ER PT J AU Bandopadhayay, P Ramkissoon, S Hwang, J Ramkissoon, L Dubuc, A Schumacher, S Janeway, K Pinches, N Malkin, H Sinai, C Manley, P Wright, K Filbin, M Goumnerova, L Alexandrescu, S Harris, M Ligon, A Kieran, M Chi, S Beroukhim, R Ligon, K AF Bandopadhayay, Pratiti Ramkissoon, Shakti Hwang, Jaeho Ramkissoon, Lori Dubuc, Adrian Schumacher, Steven Janeway, Katherine Pinches, Nathan Malkin, Hayley Sinai, Claire Manley, Peter Wright, Karen Filbin, Mariella Goumnerova, Liliana Alexandrescu, Sanda Harris, Marian Ligon, Azra Kieran, Mark Chi, Susan Beroukhim, Rameen Ligon, Keith TI CLINICAL TARGETED EXOME-BASED SEQUENCING IN COMBINATION WITH GENOME WIDE COPY NUMBER PROFILING: A CLIA CERTIFIED APPROACH FOR PRECISION MEDICINE IN 203 PEDIATRIC BRAIN TUMOR PATIENTS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Bandopadhayay, Pratiti; Hwang, Jaeho; Janeway, Katherine; Pinches, Nathan; Malkin, Hayley; Sinai, Claire; Manley, Peter; Wright, Karen; Filbin, Mariella; Goumnerova, Liliana; Kieran, Mark; Chi, Susan] Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA USA. [Bandopadhayay, Pratiti; Schumacher, Steven; Filbin, Mariella; Beroukhim, Rameen; Ligon, Keith] Broad Inst MIT & Harvard, Cambridge, MA USA. [Alexandrescu, Sanda; Harris, Marian] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. [Ramkissoon, Shakti; Hwang, Jaeho; Ramkissoon, Lori; Malkin, Hayley; Sinai, Claire; Ligon, Keith] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ramkissoon, Shakti; Dubuc, Adrian] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Dubuc, Adrian; Ligon, Azra] Brigham & Womens Hosp, Cytogenet Div, Ctr Adv Mol Diagnost, 75 Francis St, Boston, MA 02115 USA. [Goumnerova, Liliana] Boston Childrens Hosp, Dept Neurosurg, Boston, MA USA. [Harris, Marian] Boston Childrens Hosp, Mol Pathol, Boston, MA USA. [Schumacher, Steven; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA EPT-20 BP 28 EP 28 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000109 ER PT J AU Marinoff, A Guo, DJ Ma, C Snuderl, M Wright, K Manley, P Malkin, H Ullrich, N Marcus, K Goumnerova, L London, W Fangusaro, J Kieran, M Chi, SS Bandopadhayay, P AF Marinoff, Amanda Guo, Dongjing Ma, Clement Snuderl, Matija Wright, Karen Manley, Peter Malkin, Hayley Ullrich, Nicole Marcus, Karen Goumnerova, Liliana London, Wendy Fangusaro, Jason Kieran, Mark Chi, Susan Bandopadhayay, Pratiti TI PEDIATRIC EPENDYMOMA: MULTI-INSTITUTIONAL EXPERIENCE REVEALS POOR LONG-TERM OVERALL SURVIVAL DESPITE FAVORABLE FIVE-YEAR OUTCOMES SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Marinoff, Amanda; Guo, Dongjing; Ma, Clement; Snuderl, Matija; Wright, Karen; Manley, Peter; Malkin, Hayley; Ullrich, Nicole; Marcus, Karen; Goumnerova, Liliana; London, Wendy; Kieran, Mark; Chi, Susan; Bandopadhayay, Pratiti] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. [Marinoff, Amanda; Guo, Dongjing; Ma, Clement; Snuderl, Matija; Wright, Karen; Manley, Peter; Malkin, Hayley; Ullrich, Nicole; Marcus, Karen; Goumnerova, Liliana; London, Wendy; Kieran, Mark; Chi, Susan; Bandopadhayay, Pratiti] Harvard Med Sch, Boston, MA USA. [Fangusaro, Jason] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA EPN-14 BP 33 EP 33 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000125 ER PT J AU Hoffman, LM van Zanten, SEMV Colditz, N Baugh, J Chaney, B Lane, A Fuller, C Miles, L Hawkins, C Bartels, U Bouffet, E Goldman, S Leary, S Foreman, NK Packer, R Warren, KE Broniscer, A Kieran, MW Minturn, J Comito, M Broxon, E Shih, CS Khatua, S Chintagumpala, M Carret, AS Hassall, T Ziegler, D Gottardo, N Dholaria, H Lerme, B Kirkendall, J Doughman, R Hoffmann, M Wollman, M O'Keefe, R Benesch, M Gerber, N Bailey, S Solanki, G Massimino, M Biassoni, V Cvrlje, FJ Hulleman, E Drissi, R Nazarian, J Jabado, N von Bueren, AO Pietsch, T Gielen, GH Sturm, D Jones, DT Pfister, S Jones, C Hargrave, D Sanchez, E Bison, B Warmuth-Metz, M Leach, J Jones, B van Vuurden, DG Kramm, CM Fouladi, M AF Hoffman, Lindsey M. van Zanten, Sophie E. M. Veldhuijzen Colditz, Niclas Baugh, Joshua Chaney, Brooklyn Lane, Adam Fuller, Christine Miles, Lili Hawkins, Cynthia Bartels, Ute Bouffet, Eric Goldman, Stewart Leary, Sarah Foreman, Nicholas K. Packer, Roger Warren, Katherine E. Broniscer, Alberto Kieran, Mark W. Minturn, Jane Comito, Melanie Broxon, Emmett Shih, Chie-Schin Khatua, Soumen Chintagumpala, Murali Carret, Anne-Sophie Hassall, Timothy Ziegler, David Gottardo, Nick Dholaria, Hetal Lerme, Brianna Kirkendall, Jenavieve Doughman, Renee Hoffmann, Marion Wollman, Matthew O'Keefe, Rachel Benesch, Martin Gerber, Nicolas Bailey, Simon Solanki, Guirish Massimino, Maura Biassoni, Veronica Cvrlje, Filip Jadrijevic Hulleman, Esther Drissi, Rachid Nazarian, Javad Jabado, Nada von Bueren, Andre Oscar Pietsch, Torsten Gielen, Gerrit H. Sturm, Dominik Jones, David T. Pfister, Stefan Jones, Chris Hargrave, Darren Sanchez, Esther Bison, Brigitte Warmuth-Metz, Monika Leach, James Jones, Blaise van Vuurden, Dannis G. Kramm, Christof M. Fouladi, Maryam TI CLINICAL, RADIOLOGICAL, AND HISTO-GENETIC CHARACTERISTICS OF LONG-TERM SURVIVORS OF DIFFUSE INTRINSIC PONTINE GLIOMA: A COLLABORATIVE REPORT FROM THE INTERNATIONAL AND SIOP-E DIPG REGISTRIES SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Hoffman, Lindsey M.; Baugh, Joshua; Chaney, Brooklyn; Lane, Adam; Fuller, Christine; Miles, Lili; Lerme, Brianna; Kirkendall, Jenavieve; Doughman, Renee; Wollman, Matthew; O'Keefe, Rachel; Drissi, Rachid; Leach, James; Jones, Blaise; Fouladi, Maryam] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [van Zanten, Sophie E. M. Veldhuijzen; Hulleman, Esther; Sanchez, Esther; van Vuurden, Dannis G.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Colditz, Niclas; Hoffmann, Marion; von Bueren, Andre Oscar; Pietsch, Torsten; Gielen, Gerrit H.; Sturm, Dominik; Jones, David T.; Pfister, Stefan; Bison, Brigitte; Warmuth-Metz, Monika; Kramm, Christof M.] Univ Med Ctr Goettingen, Gottingen, Germany. [Hawkins, Cynthia; Bartels, Ute; Bouffet, Eric] Hosp Sick Children, Toronto, ON, Canada. [Goldman, Stewart] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Leary, Sarah] Seattle Childrens Hosp, Seattle, WA USA. [Foreman, Nicholas K.] Childrens Hosp Colorado, Aurora, CO USA. [Packer, Roger; Nazarian, Javad] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Warren, Katherine E.] NCI, NIH, Bethesda, MD 20892 USA. [Broniscer, Alberto] St Jude Childrens Res Hosp, Memphis, TN USA. [Kieran, Mark W.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. [Minturn, Jane] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Comito, Melanie] Penn State Hershey Childrens Hosp, Hummelstown, PA USA. [Broxon, Emmett] Dayton Childrens Hosp, Dayton, OH USA. [Shih, Chie-Schin] Riley Childrens Hosp, Indianapolis, IN USA. [Khatua, Soumen] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Chintagumpala, Murali] Texas Childrens Hosp, Houston, TX 77030 USA. [Carret, Anne-Sophie] CHU St Justine, Montreal, PQ, Canada. [Hassall, Timothy] Lady Cilento Chidlrens Hosp, Brisbane, Qld, Australia. [Ziegler, David] Sydney Childrens Hosp, Sydney, NSW, Australia. [Gottardo, Nick; Dholaria, Hetal] Telethon Kids Inst, Perth, Australia. [Benesch, Martin] Med Univ Graz, Graz, Austria. [Gerber, Nicolas; von Bueren, Andre Oscar] Univ Hosp Geneva, Geneva, Switzerland. [Bailey, Simon] Great North Childrens Hosp, New Castle, England. [Solanki, Guirish] Univ Birmingham, Birmingham, W Midlands, England. [Massimino, Maura; Biassoni, Veronica] Fdn IRCCS Inst Nazl Tumori, Milan, Italy. [Cvrlje, Filip Jadrijevic] Childrens Hosp Zagreb, Zagreb, Croatia. [Jabado, Nada] Montreal Childrens Hosp, Montreal, PQ H3H 1P3, Canada. [Jones, Chris] Inst Canc Res, Sutton, Surrey, England. [Hargrave, Darren] Great Ormond St Hosp Sick Children, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA HG-75 BP 65 EP 66 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000250 ER PT J AU Wright, KD Bandopadhayay, P Gourmnerova, L Chi, SN Manley, P Marcus, K Kannan, G Banerjee, A Becher, O Bendel, A Bowers, D Bredlau, AL Cohen, K Comito, M Elster, JD Etzl, M Fisher, PG Gardner, S Goldman, S Gururangan, S Handler, MH Jabado, N Karajannis, M Khatib, Z Leary, SE MacDonald, TJ Monje, M Nazemi, K Robison, NJ Rubin, J Sandler, ES Snuderl, M Wang, ZJ Sinai, CE Greenspan, L Lawler, K Neuberg, D Filbin, M Segal, R Suva, ML Beroukhim, R Ligon, K Gupta, N Prados, M Kieran, M AF Wright, Karen D. Bandopadhayay, Pratiti Gourmnerova, Liliana Chi, Susan N. Manley, Peter Marcus, Karen Kannan, Geoffrey Banerjee, Anu Becher, Oren Bendel, Anne Bowers, Daniel Bredlau, Amy-Lee Cohen, Kenneth Comito, Melani Elster, Jennifer D. Etzl, Michael Fisher, Paul G. Gardner, Sharon Goldman, Stewart Gururangan, Sridharan Handler, Michael H. Jabado, Nada Karajannis, Matthias Khatib, Ziad Leary, Sarah E. MacDonald, Tobey J. Monje, Michelle Nazemi, Kellie Robison, Nathan J. Rubin, Joshua Sandler, Eric S. Snuderl, Matija Wang, Zhihong Joanne Sinai, Claire E. Greenspan, Lianne Lawler, Kristen Neuberg, Donna Filbin, Mariella Segal, Rosalind Suva, Mario L. Beroukhim, Rameen Ligon, Keith Gupta, Nalin Prados, Michael Kieran, Markw. TI SAFETY AND FEASIBILITY OF A MULTI-INSTITUTIONAL PHASE II TRIAL INCOPORATING BIOPSY AND MOLECULARLY DETERMINED TREATMENT OF CHILDREN AND YOUNG ADULTS WITH NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMAS (DIPG) SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Wright, Karen D.; Bandopadhayay, Pratiti; Gourmnerova, Liliana; Chi, Susan N.; Manley, Peter; Marcus, Karen; Kannan, Geoffrey; Sinai, Claire E.; Greenspan, Lianne; Lawler, Kristen; Neuberg, Donna; Filbin, Mariella; Segal, Rosalind; Suva, Mario L.; Beroukhim, Rameen; Ligon, Keith; Kieran, Markw.] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Bandopadhayay, Pratiti; Filbin, Mariella; Suva, Mario L.; Beroukhim, Rameen; Ligon, Keith] Broad Inst, Cambridge, MA USA. [Banerjee, Anu; Gupta, Nalin; Prados, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Becher, Oren; Gururangan, Sridharan] Duke Univ, Med Ctr, Durham, NC USA. [Bendel, Anne] Childrens Hosp, Minneapolis, MN USA. [Bendel, Anne] Clin Minnesota, Minneapolis, MN USA. [Bowers, Daniel] UT Southwestern Med Ctr, Dallas, TX USA. [Bredlau, Amy-Lee] Med Univ South Carolina, Charleston, SC USA. [Cohen, Kenneth] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Comito, Melani] Penn State Hershey Childrens Hosp, Hershey, PA USA. [Elster, Jennifer D.] Kosair Childrens Hosp, Louisville, KY USA. [Etzl, Michael] Phoenix Childrens Hosp, Phoenix, AZ USA. [Fisher, Paul G.; Monje, Michelle] Lucile Packard Childrens Hosp Stanford, Palo Alto, CA USA. [Gardner, Sharon; Karajannis, Matthias; Snuderl, Matija] NYU, Langone Med Ctr, New York, NY USA. [Goldman, Stewart] Lurie Childrens Hosp, Chicago, IL USA. [Handler, Michael H.] Childrens Hosp Colorado, Aurora, CO USA. [Jabado, Nada] McGill Univ, Ctr Hlth, Montreal Childrens Hosp, Montreal, PQ, Canada. [Khatib, Ziad] Nicklaus Childrens Hosp, Miami, FL USA. [Leary, Sarah E.] Seattle Childrens Hosp, Seattle, WA USA. [MacDonald, Tobey J.] Emory Univ, Sch Med, Childrens Healthcare Atlanta, Atlanta, GA USA. [Nazemi, Kellie] Oregon Hlth Sci Univ Hosp, Portland, OR USA. [Robison, Nathan J.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Rubin, Joshua] Washington Univ, Siteman Canc Ctr, Med Campus, St Louis, MO USA. [Sandler, Eric S.] Nemours Childrens Specialty Care, Jacksonville, FL USA. [Wang, Zhihong Joanne] Wayne State Univ, Childrens Hosp Michigan, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA HG-73 BP 65 EP 65 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000248 ER PT J AU Panditharatna, E Nikbakht, H Mikael, L Li, R Gayden, T Osmand, M Ho, CY Kambhampati, M Hwang, EI Faury, D Siu, A Papillon-Cavanagh, S Bechet, D Ligon, KL Ellezam, B Ingram, WJ Stinson, C Moore, AS Warren, KE Karamchandani, J Packer, RJ Jabado, N Majewski, J Nazarian, J AF Panditharatna, Eshini Nikbakht, Hamid Mikael, Leonie Li, Rui Gayden, Tenzin Osmand, Matthew Ho, Cheng-Ying Kambhampati, Madhuri Hwang, Eugene I. Faury, Damien Siu, Alan Papillon-Cavanagh, Simon Bechet, Denise Ligon, Keith L. Ellezam, Benjamin Ingram, Wendy J. Stinson, Caedyn Moore, Andrew S. Warren, Katherine E. Karamchandani, Jason Packer, Roger J. Jabado, Nada Majewski, Jacek Nazarian, Javad TI SPATIAL AND TEMPORAL HOMOGENEITY OF DRIVER MUTATIONS IN DIFFUSE INTRINSIC PONTINE GLIOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Panditharatna, Eshini; Ho, Cheng-Ying; Kambhampati, Madhuri; Hwang, Eugene I.; Packer, Roger J.; Nazarian, Javad] Childrens Natl Hlth Syst, Washington, DC USA. [Panditharatna, Eshini; Ho, Cheng-Ying; Kambhampati, Madhuri; Siu, Alan; Packer, Roger J.; Nazarian, Javad] George Washington Univ, Washington, DC USA. [Nikbakht, Hamid; Mikael, Leonie; Li, Rui; Gayden, Tenzin; Osmand, Matthew; Faury, Damien; Papillon-Cavanagh, Simon; Bechet, Denise; Karamchandani, Jason; Jabado, Nada; Majewski, Jacek] McGill Univ, Montreal, PQ, Canada. [Ligon, Keith L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ellezam, Benjamin] Univ Montreal, Montreal, PQ, Canada. [Ingram, Wendy J.; Stinson, Caedyn; Moore, Andrew S.] Univ Queensland, Brisbane, Qld, Australia. [Warren, Katherine E.] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA HG-76 BP 66 EP 66 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000251 ER PT J AU Cooney, T League-Pascual, J Lane, A Hoffman, L Bartels, U Bouffet, E Goldman, S Leary, S Foreman, N Packer, R Broniscer, A Kieran, M Minturn, J Comito, M Broxon, E Shih, CS Khatua, S Chintagumpala, M Carret, A Hassall, T Gottardo, N Baugh, J Chaney, B Doughman, R Leach, J Jones, B Fouladi, M Monje, M Warren, K AF Cooney, Tabitha League-Pascual, James Lane, Adam Hoffman, Lindsey Bartels, Ute Bouffet, Eric Goldman, Stewart Leary, Sarah Foreman, Nicholas Packer, Roger Broniscer, Alberto Kieran, Mark Minturn, Jane Comito, Melanie Broxon, Emmett Shih, Chie-Schin Khatua, Soumen Chintagumpala, Murali Carret, Anne Hassall, Tim Gottardo, Nick Baugh, Joshua Chaney, Brooklyn Doughman, Renee Leach, James Jones, Blaise Fouladi, Maryam Monje, Michelle Warren, Kathy TI CONTEMPORARY SURVIVAL ENDPOINTS: AN INTERNATIONAL DIFFUSE INTRINSIC PONTINE GLIOMA REGISTRY STUDY SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Cooney, Tabitha; Monje, Michelle] Stanford Univ, Palo Alto, CA 94304 USA. [League-Pascual, James; Warren, Kathy] NCI, Bethesda, MD 20892 USA. [Lane, Adam; Hoffman, Lindsey; Baugh, Joshua; Chaney, Brooklyn; Doughman, Renee; Leach, James; Jones, Blaise; Fouladi, Maryam] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Bartels, Ute; Bouffet, Eric] Hosp Sick Children, Toronto, ON, Canada. [Goldman, Stewart] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Chintagumpala, Murali] Texas Childrens Hosp, Houston, TX 77030 USA. [Khatua, Soumen] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Shih, Chie-Schin] Riley Hosp Children, Indianapolis, IN USA. [Packer, Roger] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Broniscer, Alberto] St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA. [Comito, Melanie] Penn State Childrens Hosp, Hershey, PA USA. [Minturn, Jane] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Kieran, Mark] Dana Farber Canc Inst, Boston, MA 02115 USA. [Foreman, Nicholas] Childrens Hosp Colorado, Denver, CO USA. [Leary, Sarah] Seattle Childrens, Seattle, WA USA. [Broxon, Emmett] Dayton Childrens Hosp, Dayton, OH USA. [Carret, Anne] CHU St Justine, Montreal, PQ, Canada. [Hassall, Tim] Lady Cilento Childrens Hosp, South Brisbane, Qld, Australia. [Gottardo, Nick] Telethon Kids Inst, Perth, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA HG-109 BP 73 EP 74 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000284 ER PT J AU Filbin, MG Tirosh, I Escalante, LE Venteicher, AS Goumnerova, L Pelton, K Bandopadhayay, P Mount, C Slavc, I Czech, T Gojo, J Lavarino, C Mora, J Monje, M Kieran, MW Ligon, KL Golub, T Regev, A Suva, ML AF Filbin, Mariella G. Tirosh, Itay Escalante, Leah E. Venteicher, Andrew S. Goumnerova, Liliana Pelton, Kristine Bandopadhayay, Pratiti Mount, Christopher Slavc, Irene Czech, Thomas Gojo, Johannes Lavarino, Cinzia Mora, Jaume Monje, Michelle Kieran, Mark W. Ligon, Keith L. Golub, Todd Regev, Aviv Suva, Mario L. TI SINGLE-CELL TRANSCRIPTOME ANALYSIS IN PEDIATRIC HEMISPHERIC AND MIDLINE HIGH-GRADE GLIOMAS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Filbin, Mariella G.; Escalante, Leah E.; Venteicher, Andrew S.; Goumnerova, Liliana; Pelton, Kristine; Bandopadhayay, Pratiti; Kieran, Mark W.; Ligon, Keith L.; Golub, Todd; Suva, Mario L.] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Filbin, Mariella G.; Tirosh, Itay; Escalante, Leah E.; Venteicher, Andrew S.; Bandopadhayay, Pratiti; Golub, Todd; Regev, Aviv; Suva, Mario L.] Broad Inst, Cambridge, MA USA. [Goumnerova, Liliana; Pelton, Kristine; Kieran, Mark W.; Ligon, Keith L.] Boston Childrens Hosp, Boston, MA USA. [Mount, Christopher; Monje, Michelle] Stanford Univ, Palo Alto, CA 94304 USA. [Slavc, Irene; Czech, Thomas; Gojo, Johannes] Med Univ Vienna, Vienna, Austria. [Lavarino, Cinzia; Mora, Jaume] Hosp St Joan de Deu Barcelona, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA HG-110 BP 74 EP 74 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000285 ER PT J AU Green, A Flannery, P DeSisto, J Lemieux, M Ramkissoon, S Jones, K Perry, J Hubbell-Engler, B DeRyckere, D Venkataraman, S Foreman, N Orkin, S Ligon, K Jones, K Graham, D Kung, A Vibhakar, R AF Green, Adam Flannery, Patrick DeSisto, John Lemieux, Madeleine Ramkissoon, Shak Jones, Kristen Perry, Jennifer Hubbell-Engler, Benjamin DeRyckere, Deborah Venkataraman, Sujatha Foreman, Nicholas Orkin, Stuart Ligon, Keith Jones, Ken Graham, Doug Kung, Andrew Vibhakar, Rajeev TI AN EPIGENOMIC SCREEN REVEALS THE CHROMATIN REMODELING PROTEIN BPTF AS A DRIVER OF HIGH-GRADE GLIOMA AND DIFFUSE INTRINSIC PONTINE GLIOMA GROWTH IN VITRO AND IN VIVO SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Green, Adam; Flannery, Patrick; DeSisto, John; Venkataraman, Sujatha; Foreman, Nicholas; Jones, Ken; Vibhakar, Rajeev] Univ Colorado, Sch Med, Aurora, CO USA. [Green, Adam; Foreman, Nicholas; Vibhakar, Rajeev] Childrens Hosp Colorado, Aurora, CO USA. [Lemieux, Madeleine] Bioinfo, Ottawa, ON, Canada. [Ramkissoon, Shak; Jones, Kristen; Perry, Jennifer; Hubbell-Engler, Benjamin; Orkin, Stuart; Ligon, Keith] Dana Farber Canc Inst, Boston, MA 02115 USA. [DeRyckere, Deborah; Graham, Doug] Emory Univ, Atlanta, GA 30322 USA. [Kung, Andrew] Columbia Univ, Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA HG-123 BP 76 EP 76 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000298 ER PT J AU Bergthold, G Bandopadhayay, P Ramkissoon, L Jain, P Wala, J Schumacher, S Ramkissoon, S Varlet, P Pages, M Ducar, M Van Hummelen, P Bowers, D Giannini, C Puget, S Hawkins, C Tabori, U Klekner, A Bognar, L Burger, P Eberhart, C Rodriguez, F Hill, DA Muller, S Haas-Kogan, D Phillips, J Santagata, S Stiles, C Bradner, J Jabado, N Goren, A Grill, J Ligon, A Goumnerova, L Waanders, A Storm, P Kieran, M Resnick, A Ligon, K Beroukhim, R AF Bergthold, Guillaume Bandopadhayay, Pratiti Ramkissoon, Lori Jain, Payal Wala, Jeremiah Schumacher, Steven Ramkissoon, Shakti Varlet, Pascale Pages, Melanie Ducar, Matthew Van Hummelen, Paul Bowers, Daniel Giannini, Caterina Puget, Stephanie Hawkins, Cynthia Tabori, Uri Klekner, Almos Bognar, Laszlo Burger, Peter Eberhart, Charles Rodriguez, Fausto Hill, D. Ashley Muller, Sabine Haas-Kogan, Daphne Phillips, Joanna Santagata, Sandro Stiles, Charles Bradner, James Jabado, Nada Goren, Alon Grill, Jacques Ligon, Azra Goumnerova, Liliana Waanders, Angela Storm, Philip Kieran, Mark Resnick, Adam Ligon, Keith Beroukhim, Rameen TI MYB-QKI REARRANGEMENTS IN ANGIOCENTRIC GLIOMA DRIVE TUMORIGENICITY THROUGH A TRIPARTITE MECHANISM SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Bergthold, Guillaume; Bandopadhayay, Pratiti; Wala, Jeremiah; Schumacher, Steven; Santagata, Sandro; Stiles, Charles; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Bandopadhayay, Pratiti; Kieran, Mark] Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA USA. [Wala, Jeremiah; Schumacher, Steven; Goren, Alon; Beroukhim, Rameen] Broad Inst, Cambridge, MA USA. [Ramkissoon, Lori; Ramkissoon, Shakti; Bradner, James; Ligon, Keith] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Jain, Payal; Storm, Philip; Resnick, Adam] Childrens Hosp Philadelphia, Div Neurosurg, Philadelphia, PA 19104 USA. [Storm, Philip; Resnick, Adam] Univ Penn, Perelman Sch Med, Dept Neurosurg, Philadelphia, PA 19104 USA. [Jain, Payal] Univ Penn, Perelman Sch Med, Gene Therapy & Vaccines Program, Cell & Mol Biol Grad Grp, Philadelphia, PA 19104 USA. [Bergthold, Guillaume; Grill, Jacques] Univ Paris 11, Dept Cancerol Enfant & Adolescent, Villejuif, France. [Bergthold, Guillaume; Grill, Jacques] Univ Paris 11, Gustave Roussy, CNRS, UMR 8203, Villejuif, France. [Ramkissoon, Shakti; Santagata, Sandro; Ligon, Keith] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Varlet, Pascale; Pages, Melanie] Univ Paris 05, Hop St Anne, Lab Neuropathol, Paris, France. [Goumnerova, Liliana] Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St, Boston, MA 02115 USA. [Ducar, Matthew; Van Hummelen, Paul] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Bowers, Daniel] UT Southwestern Med Sch, Div Pediat Hematol Oncol, Dallas, TX USA. [Giannini, Caterina] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Puget, Stephanie] Univ Paris 05, Hop Necker Enfants Malad, Dept Neurochirurg, Paris, France. [Hawkins, Cynthia] Hosp Sick Children, Dept Pathol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. [Tabori, Uri] Hosp Sick Children, Div Hematol Oncol, Toronto, ON, Canada. [Klekner, Almos; Bognar, Laszlo; Burger, Peter] Univ Debrecen, Med & Hlth Sci Ctr, Dept Neurosurg, Debrecen, Hungary. [Eberhart, Charles; Rodriguez, Fausto] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Eberhart, Charles; Rodriguez, Fausto] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. [Eberhart, Charles; Rodriguez, Fausto] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Hill, D. Ashley] Childrens Natl Med Ctr, Brain Tumor Inst, Washington, DC 20010 USA. [Hill, D. Ashley] Childrens Natl Med Ctr, Brain Tumor Inst, Ctr Neurosci & Behav Med, Washington, DC 20010 USA. [Muller, Sabine] Univ Calif San Francisco, Sch Med, Dept Neurol Neurosurg & Pediat, San Francisco, CA USA. [Haas-Kogan, Daphne; Bradner, James] Univ Calif San Francisco, Dept Radiat Oncol, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Phillips, Joanna] Univ Calif San Francisco, Dept Pathol, Div Neuropathol, San Francisco, CA 94140 USA. [Jabado, Nada] McGill Univ, Dept Human Genet, Montreal, PQ, Canada. [Jabado, Nada] McGill Univ, Dept Pediat, Montreal, PQ, Canada. [Ligon, Azra] Brigham & Womens Hosp, Dept Pathol, Ctr Adv Mol Diagnost, Cytogenet Div, 75 Francis St, Boston, MA 02115 USA. [Goumnerova, Liliana] Boston Childrens Hosp, Dept Neurosurg, Boston, MA USA. [Waanders, Angela] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. NR 0 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 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA LG-02 BP 78 EP 78 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000305 ER PT J AU Kieran, MW Sun, Y Pilarz, C Calligaris, D Chadwick, EJ Alberta, JA Ramkissoon, SH Ramkissoon, LA Garcia, VM Wilkinson, K Kane, M Goumnerova, L Chi, SN Manley, P Wright, KD Agar, NY Ligon, KL Beroukhim, R Bandopadhayay, P Kannan, G Segal, RA Garraway, LA Gray, NS Eck, M Stiles, CD Buhrlage, SJ AF Kieran, Mark W. Sun, Yu Pilarz, Catherine Calligaris, David Chadwick, Emily J. Alberta, John A. Ramkissoon, Shakti H. Ramkissoon, Lori A. Garcia, Veronica Matia Wilkinson, Kim Kane, Michael Goumnerova, Liliana Chi, Susan N. Manley, Peter Wright, Karen D. Agar, Nathalie Y. Ligon, Keith L. Beroukhim, Rameen Bandopadhayay, Pratiti Kannan, Geoffrey Segal, Rosalind A. Garraway, Levi A. Gray, Nathanael S. Eck, Michael Stiles, Charles D. Buhrlage, Sara J. TI TYPE II RAF INHIBITORS INHIBIT BRAF MUTATIONS AND TRUNCATED FUSIONS IN PEDIATRIC LOW-GRADE GLIOMAS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Kieran, Mark W.; Sun, Yu; Pilarz, Catherine; Chadwick, Emily J.; Alberta, John A.; Ramkissoon, Shakti H.; Ramkissoon, Lori A.; Garcia, Veronica Matia; Wilkinson, Kim; Kane, Michael; Goumnerova, Liliana; Chi, Susan N.; Manley, Peter; Wright, Karen D.; Agar, Nathalie Y.; Ligon, Keith L.; Beroukhim, Rameen; Bandopadhayay, Pratiti; Kannan, Geoffrey; Segal, Rosalind A.; Garraway, Levi A.; Gray, Nathanael S.; Eck, Michael; Stiles, Charles D.; Buhrlage, Sara J.] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Kieran, Mark W.; Ramkissoon, Shakti H.; Goumnerova, Liliana; Chi, Susan N.; Manley, Peter; Wright, Karen D.; Bandopadhayay, Pratiti; Kannan, Geoffrey] Harvard Med Sch, Boston Childrens Hosp, Boston, MA USA. [Calligaris, David; Agar, Nathalie Y.; Ligon, Keith L.; Beroukhim, Rameen] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA LG-47 BP 89 EP 89 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000350 ER PT J AU Lassaletta, A Mistry, M Arnaldo, A Ryall, S Guerreiro-Stucklin, A Krishnatry, R Ling, CN Honnorat, M Zhukova, N Zapotocky, M McKeown, T Ramaswamy, V Bartels, U Huang, A Jabado, N Cruz, O de Torres, C Cherry, H Packer, R Tatevossian, R Ellison, D Harreld, J Dalton, J Mulcahy-Levy, J Foreman, N Karajannis, M Mueller, S Nicolaides, T Eisenstat, D Carret, AS Kieran, M Ligon, K Jouvet, A Perbert, R Vasiljevic, A Frappaz, D Joly, MO Chambeless, L Thompson, R Rao, AN Chan, A Ng, H Garre, ML Nozza, P Massimino, M Leary, S Crane, C Bouffet, E Hawkins, C Tabori, U AF Lassaletta, Alvaro Mistry, Matthew Arnaldo, Anthony Ryall, Scott Guerreiro-Stucklin, Ana Krishnatry, Rahul Ling, Cino Honnorat, Marion Zhukova, Nataliya Zapotocky, Michal McKeown, Tara Ramaswamy, Vijay Bartels, Ute Huang, Annie Jabado, Nada Cruz, Ofelia de Torres, Carmen Cherry, Ho Packer, Roger Tatevossian, Ruth Ellison, David Harreld, Julie Dalton, Jim Mulcahy-Levy, Jean Foreman, Nicholas Karajannis, Matthias Mueller, Sabine Nicolaides, Theodore Eisenstat, David Carret, Anne-Sophie Kieran, Mark Ligon, Keith Jouvet, Anne Perbert, Romain Vasiljevic, Alex Frappaz, Didier Joly, Marie Odile Chambeless, Lola Thompson, Reid Rao, Amulya Nageswara Chan, Aden Ng, Hk Garre, Maria Luisa Nozza, Paolo Massimino, Maura Leary, Sarah Crane, Courtney Bouffet, Eric Hawkins, Cynthia Tabori, Uri TI INFERIOR OUTCOME AND POOR RESPONSE TO CONVENTIONAL THERAPIES IN PEDIATRIC LOW-GRADE GLIOMAS HARBORING THE BRAF V600E MUTATION SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Lassaletta, Alvaro; Mistry, Matthew; Arnaldo, Anthony; Ryall, Scott; Guerreiro-Stucklin, Ana; Krishnatry, Rahul; Ling, Cino; Honnorat, Marion; Zhukova, Nataliya; Zapotocky, Michal; McKeown, Tara; Ramaswamy, Vijay; Bartels, Ute; Huang, Annie; Jabado, Nada; Bouffet, Eric; Hawkins, Cynthia; Tabori, Uri] Hosp Sick Children, Toronto, ON, Canada. [Cruz, Ofelia; de Torres, Carmen] Hosp St Joan de Deu, Barcelona, Spain. [Cherry, Ho; Packer, Roger] Childrens Hosp Washington, Washington, DC USA. [Tatevossian, Ruth; Ellison, David; Harreld, Julie; Dalton, Jim] St Jude Childrens Res Hosp, Memphis, TN USA. [Mulcahy-Levy, Jean; Foreman, Nicholas] Childrens Hosp Colorado, Aurora, CO USA. [Karajannis, Matthias] Langone Med Ctr, New York, NY USA. [Mueller, Sabine; Nicolaides, Theodore] UCSF Childrens Hosp, San Francisco, CA USA. [Eisenstat, David] Canc Res Inst Northern Alberta, Edmonton, AB, Canada. [Carret, Anne-Sophie] Ctr Hosp Univ St Justine, St Justine, PQ, Canada. [Kieran, Mark; Ligon, Keith] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jouvet, Anne; Perbert, Romain; Vasiljevic, Alex; Frappaz, Didier; Joly, Marie Odile] Hosp Femme Mere Enfant, Lyon, France. [Chambeless, Lola; Thompson, Reid] Vanderbilt Univ, Memphis, TN USA. [Rao, Amulya Nageswara] Mayo Clin, Coll Med, Rochester, MN USA. [Chan, Aden; Ng, Hk] Prince Wales Hosp, Hong Kong, Hong Kong, Peoples R China. [Garre, Maria Luisa; Nozza, Paolo] Ist Giannina Gaslini, Genoa, Italy. [Massimino, Maura] Ist Tumori, Milan, Italy. [Leary, Sarah; Crane, Courtney] Canc & Blood Disorders Ctr, Seattle, WA USA. NR 0 TC 1 Z9 1 U1 3 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA LG-46 BP 89 EP 89 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000349 ER PT J AU Zhukova, N Krishnatry, R Stucklin, ASG Pole, JD Mistry, M Fried, I Ramaswamy, V Bartels, U Huang, A Laperriere, N Dirks, P Nathan, PC Greenberg, M Malkin, D Hawkins, C Bandopadhayay, P Kieran, M Manley, PE Bouffet, E Tabori, U AF Zhukova, Nataliya Krishnatry, Rahul Stucklin, Ana S. Guerreiro Pole, Jason D. Mistry, Matthew Fried, Iris Ramaswamy, Vijay Bartels, Ute Huang, Annie Laperriere, Normand Dirks, Peter Nathan, Paul C. Greenberg, Mark Malkin, David Hawkins, Cynthia Bandopadhayay, Pratiti Kieran, Markw. Manley, Peter E. Bouffet, Eric Tabori, Uri TI CLINICAL AND TREATMENT FACTORS DETERMINING LONG-TERM OUTCOMES FOR ADULT SURVIVORS OF CHILDHOOD LOW-GRADE GLIOMA: A POPULATION-BASED STUDY SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Zhukova, Nataliya; Krishnatry, Rahul; Stucklin, Ana S. Guerreiro; Ramaswamy, Vijay; Bartels, Ute; Huang, Annie; Laperriere, Normand; Nathan, Paul C.; Greenberg, Mark; Malkin, David; Bouffet, Eric; Tabori, Uri] Hosp Sick Children, Div Haematol Oncol, Toronto, ON, Canada. [Zhukova, Nataliya; Krishnatry, Rahul; Mistry, Matthew; Dirks, Peter; Hawkins, Cynthia; Tabori, Uri] Hosp Sick Children, Labatt Brain Tumor Res Ctr, Toronto, ON, Canada. [Laperriere, Normand] Princess Margaret Hosp, Radiat Med, Toronto, ON, Canada. [Malkin, David] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON, Canada. [Pole, Jason D.; Greenberg, Mark] Paediat Oncol Grp Ontario, Toronto, ON, Canada. [Mistry, Matthew] Univ Toronto, Inst Med Sci, Toronto, ON, Canada. [Fried, Iris] Hadassah Med Ctr, Jerusalem, Israel. [Ramaswamy, Vijay; Bartels, Ute; Huang, Annie; Nathan, Paul C.; Bouffet, Eric] Univ Toronto, Dept Paediat, Toronto, ON, Canada. [Dirks, Peter] Hosp Sick Children, Div Neurosurg, Toronto, ON, Canada. [Hawkins, Cynthia] Hosp Sick Children, Div Pathol, Toronto, ON, Canada. [Bandopadhayay, Pratiti; Kieran, Markw.; Manley, Peter E.] Boston Childrens Hosp, Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA USA. [Bandopadhayay, Pratiti] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA LG-66 BP 94 EP 94 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000369 ER PT J AU Warren, K Harreld, J Chamberlain, M Vezina, G Warmuth-Metz, M von Hoff, K Packer, R Brandes, A Reiss, M Goldman, S Fisher, M Poussaint, T Pollack, I Prados, M Wen, P Chang, S Dufour, C Zurakowski, D Kortmann, RD Kieran, M AF Warren, Kathy Harreld, Julie Chamberlain, Marc Vezina, Gilbert Warmuth-Metz, Monika von Hoff, Katja Packer, Roger Brandes, Alba Reiss, Moshe Goldman, Stewart Fisher, Michael Poussaint, Tina Pollack, Ian Prados, Michael Wen, Patrick Chang, Susan Dufour, Christelle Zurakowski, David Kortmann, Rolf-Dieter Kieran, Mark TI RESPONSE ASSESSMENT IN PEDIATRIC NEURO-ONCOLOGY (RAPNO) COMMITTEE GUIDELINES FOR RESPONSE ASSESSMENT IN MEDULLOBLASTOMA AND OTHER LEPTOMENINGEAL SEEDING TUMORS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Warren, Kathy; Kieran, Mark] NCI, Bethesda, MD 20892 USA. [Harreld, Julie] St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA. [Chamberlain, Marc] Seattle Canc Care Alliance, Seattle, WA USA. [Vezina, Gilbert; Packer, Roger] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Warmuth-Metz, Monika] Univ Wurzburg, Wurzburg, Germany. [von Hoff, Katja] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany. [Brandes, Alba] Azienda USL IRCCS Sci Neurol, Bologna, Italy. [Reiss, Moshe] Maria Fareri Childrens Hosp, Valhalla, NY USA. [Goldman, Stewart] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Fisher, Michael] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Poussaint, Tina; Zurakowski, David] Boston Childrens Hosp, Boston, MA USA. [Pollack, Ian] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Prados, Michael; Chang, Susan] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Wen, Patrick] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dufour, Christelle] Inst Gustave Roussy, Villejuif, France. [Kortmann, Rolf-Dieter] Univ Leipzig, Leipzig, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA MB-52 BP 109 EP 109 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000430 ER PT J AU Cohen, K Bandopadhayay, P London, W Chi, S Kieran, M AF Cohen, Kenneth Bandopadhayay, Pratiti London, Wendy Chi, Susan Kieran, Mark TI PILOT STUDY OF A SURGERY AND CHEMOTHERAPY-ONLY APPROACH IN THE UPFRONT THERAPY OF CHLDREN WITH Wnt POSITIVE STANDARD RISK MEDULLOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Cohen, Kenneth] Johns Hopkins Univ SOM, Baltimore, MD USA. [Bandopadhayay, Pratiti; London, Wendy; Chi, Susan; Kieran, Mark] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. NR 0 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 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA MB-66 BP 112 EP 112 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000442 ER PT J AU Peyrl, A Chocholous, M Azizi, A Kieran, M Nysom, K Sterba, J Sabel, M Czech, T Dieckmann, K Haberler, C Schmook, M Leiss, U Slavc, I AF Peyrl, Andreas Chocholous, Monika Azizi, Amedeo Kieran, Mark Nysom, Karsten Sterba, Jaroslav Sabel, Magnus Czech, Thomas Dieckmann, Karin Haberler, Christine Schmook, Maresa Leiss, Ulrike Slavc, Irene TI MEMMAT - A PHASE II STUDY OF METRONOMIC AND TARGETED ANTI-ANGIOGENESIS THERAPY FOR CHILDREN WITH RECURRENT/PROGRESSIVE MEDULLOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Peyrl, Andreas; Chocholous, Monika; Azizi, Amedeo; Czech, Thomas; Dieckmann, Karin; Haberler, Christine; Schmook, Maresa; Leiss, Ulrike; Slavc, Irene] Med Univ Vienna, Vienna, Austria. [Kieran, Mark] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kieran, Mark] Boston Childrens Hosp, Boston, MA USA. [Nysom, Karsten] Univ Rigshosp, Copenhagen, Denmark. [Sterba, Jaroslav] Univ Hosp Brno, Brno, Czech Republic. [Sabel, Magnus] Queen Silvia Childrens Hosp, Gothenburg, Sweden. NR 0 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA MB-70 BP 113 EP 113 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000446 ER PT J AU Hanaford, A Archer, T Price, A Kahlert, U Maciaczyk, J Nikkhah, G Kim, JW Ehrenberger, T Clemons, PA Dancik, V Seashore-Ludlow, B Viswanathan, V Stewart, ML Rees, MG Shamji, A Schreiber, S Fraenkel, E Pomeroy, SL Mesirov, JP Tamayo, P Eberhart, C Raabe, E AF Hanaford, Allison Archer, Tenley Price, Antoinette Kahlert, Ulf Maciaczyk, Jarek Nikkhah, Guido Kim, Jong Wook Ehrenberger, Tobias Clemons, Paul A. Dancik, Vlado Seashore-Ludlow, Brinton Viswanathan, Vasanthi Stewart, Michelle L. Rees, Matthew G. Shamji, Alykhan Schreiber, Stuart Fraenkel, Ernest Pomeroy, Scott L. Mesirov, Jill P. Tamayo, Pablo Eberhart, Charles Raabe, Eric TI DiSCoVERing INNOVATIVE THERAPIES: COMBINING GENETICALLY ACCURATE DISEASE MODELS OF MEDULLOBLASTOMA WITH ADVANCED IN SILICO ANALYSIS TO IDENTIFY NOVEL THERAPEUTIC TARGETS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Hanaford, Allison; Price, Antoinette; Eberhart, Charles; Raabe, Eric] Johns Hopkins Sch Med, Baltimore, MD USA. [Archer, Tenley; Kim, Jong Wook; Ehrenberger, Tobias; Clemons, Paul A.; Dancik, Vlado; Seashore-Ludlow, Brinton; Viswanathan, Vasanthi; Stewart, Michelle L.; Rees, Matthew G.; Shamji, Alykhan; Schreiber, Stuart; Fraenkel, Ernest; Pomeroy, Scott L.; Mesirov, Jill P.; Tamayo, Pablo] Eli & Edythe Broad Inst MIT & Harvard, Cambridge, MA USA. [Archer, Tenley; Pomeroy, Scott L.] Boston Childrens Hosp, Boston, MA USA. [Kahlert, Ulf; Maciaczyk, Jarek] Heinrich Heine Univ Hosp, Dusseldorf, Germany. [Nikkhah, Guido] Univ Hosp Stuttgart, Stuttgart, Germany. [Kim, Jong Wook] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Ehrenberger, Tobias] MIT, Boston, MA USA. [Schreiber, Stuart] Harvard Univ, Cambridge, MA 02138 USA. [Mesirov, Jill P.; Tamayo, Pablo] Univ Calif San Diego, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA MB-103 BP 120 EP 120 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000478 ER PT J AU Chang, A Yock, T Pai, A AF Chang, Andrew Yock, Torunn Pai, Atman TI THE EARLY OUTCOMES OF PROTON THERAPY FOR MEDULLOBLASTOMA ON THE PEDIATRIC PROTON CONSORTIUM REGISTRY SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Chang, Andrew] ProCure Oklahoma City, Oklahoma City, OK USA. [Yock, Torunn] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chang, Andrew; Pai, Atman] Scripps San Diego Proton Therapy Ctr, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA MB-105 BP 121 EP 121 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000480 ER PT J AU Lohkamp, LN Manley, P Kieran, MW Ullrich, N Goumnerova, LC AF Lohkamp, Laura-Nanna Manley, Peter Kieran, Mark W. Ullrich, Nicole Goumnerova, Liliana C. TI THE ROLE OF SURGERY IN NON-NF-ASSOCIATED PEDIATRIC OPTIC PATHWAY GLIOMAS (OPG) - IS THERE A NEW PARADIGM? SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Lohkamp, Laura-Nanna] Charite Uniersitatsmed, Dept Neurosurg Pediat Neurosurg, D-13353 Berlin, Germany. [Manley, Peter; Kieran, Mark W.; Ullrich, Nicole; Goumnerova, Liliana C.] Dana Farber Canc Inst, Dept Pediat Oncol, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Ullrich, Nicole] Boston Childrens Hosp, Dept Neurol, Boston, MA USA. [Lohkamp, Laura-Nanna; Goumnerova, Liliana C.] Boston Childrens Hosp, Dept Neurosurg, Boston, MA USA. Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA NS-26 BP 132 EP 132 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000527 ER PT J AU Boulos, N Kim, J Patay, Z Butch, ER Ayaz, M Snyder, SE Calabrese, C Gilbertson, RJ Wright, KD AF Boulos, Nidal Kim, Jieun Patay, Zoltan Butch, Elizabeth R. Ayaz, Muhammad Snyder, Scott E. Calabrese, Christopher Gilbertson, Richard J. Wright, Karen D. TI DIFFERENTIAL RESPONSES OF MURINE MODELS OF SUPRATENTORIAL EPENDYMOMA TO GEMCITABINE AS MEASURED BY MRI AND PET-CT SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Boulos, Nidal; Kim, Jieun; Patay, Zoltan; Butch, Elizabeth R.; Ayaz, Muhammad; Snyder, Scott E.; Calabrese, Christopher] St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA. [Gilbertson, Richard J.] Cambridge Canc Ctr, Cambridge, England. [Wright, Karen D.] Dana Farber Harvard Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA PCM-01 BP 139 EP 139 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000557 ER PT J AU Boulos, N Dapper, J Patel, Y DeCuypere, M Bianski, B Merchant, T Freeman, B Guy, R Stewart, C Wright, K Gilbertson, R AF Boulos, Nidal Dapper, Jason Patel, Yogesh DeCuypere, Michael Bianski, Brandon Merchant, Thomas Freeman, Burgess Guy, Rodney Stewart, Clinton Wright, Karen Gilbertson, Richard TI ACCURATE PRECLINICAL TRIALS OF NEW EPENDYMOMA THERAPIES SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Boulos, Nidal; Dapper, Jason; Patel, Yogesh; Bianski, Brandon; Merchant, Thomas; Freeman, Burgess; Guy, Rodney; Stewart, Clinton] St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA. [DeCuypere, Michael] Univ Tennessee Hlth Sci, Memphis, TN USA. [Wright, Karen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gilbertson, Richard] CRUK Cambridge Inst, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA PCM-06 BP 140 EP 140 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000562 ER PT J AU AbdelBaki, MS Hanzlik, E Dougherty, M Kieran, M AF AbdelBaki, Mohamed S. Hanzlik, Emily Dougherty, Mary Kieran, Mark TI MULTIDISCIPLINARY PEDIATRIC BRAIN TUMOR CLINICS: THE KEY TO SUCCESSFUL TREATMENT? SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [AbdelBaki, Mohamed S.] Nationwide Childrens Hosp, Columbus, OH USA. [AbdelBaki, Mohamed S.] Ohio State Univ, Columbus, OH 43210 USA. [Hanzlik, Emily; Dougherty, Mary] St Louis Univ, Sch Med, St Louis, MO USA. [Kieran, Mark] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. [Kieran, Mark] Harvard Med Sch, Boston Childrens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA QOS-01 BP 145 EP 145 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000579 ER PT J AU Roddy, E Sear, K Felton, E Tamrazi, B Gauvain, K Torkildson, J Del Buono, B Samuel, D Haas-Kogan, D Chen, J Goldsby, R Banerjee, A Lupo, J Molinaro, A Fullerton, H Mueller, S AF Roddy, Erika Sear, Katherine Felton, Erin Tamrazi, Benita Gauvain, Karen Torkildson, Joseph Del Buono, Benedict Samuel, David Haas-Kogan, Daphne Chen, Josephine Goldsby, Robert Banerjee, Anu Lupo, Janine Molinaro, Annette Fullerton, Heather Mueller, Sabine TI CEREBRAL MICROBLEEDS ARE ASSOCIATED WITH WORSE EXECUTIVE FUNCTION IN PEDIATRIC BRAIN TUMOR SURVIVORS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Roddy, Erika] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Gauvain, Karen] Washington Univ, Dept Pediat, St Louis, MO 63130 USA. [Torkildson, Joseph] Benioff Childrens Hosp Oakland, Oakland, CA USA. [Samuel, David] Valley Childrens Hosp, Dept Pediat, Madera, CA USA. [Haas-Kogan, Daphne] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Sear, Katherine; Felton, Erin; Tamrazi, Benita; Del Buono, Benedict; Chen, Josephine; Goldsby, Robert; Banerjee, Anu; Lupo, Janine; Molinaro, Annette; Fullerton, Heather; Mueller, Sabine] Univ Calif San Francisco, San Francisco, CA 94143 USA. FU NICHD NIH HHS [R01 HD079568] NR 0 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA RO-02 BP 159 EP 159 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000638 PM 27540084 ER PT J AU Yock, TI Goldberg, SI Vatner, RE Gaudet, DE Gallotto, SL Weyman, EA MacDonald, SM Ebb, DH Huang, M Friedmann, AM Jones, RM Tarbell, NJ Kuhlthau, KA AF Yock, Torunn I. Goldberg, Saveli I. Vatner, Ralph E. Gaudet, Dillon E. Gallotto, Sara L. Weyman, Elizabeth A. MacDonald, Shannon M. Ebb, David H. Huang, Mary Friedmann, Allison M. Jones, Robin M. Tarbell, Nancy J. Kuhlthau, Karen A. TI A PROSPECTIVE ASSESSMENT OF HRQOL OUTCOMES IN MEDULLOBLASTOMA PATIENTS TREATED WITH PROTON RADIOTHERAPY (PT) SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Yock, Torunn I.; Goldberg, Saveli I.; Vatner, Ralph E.; Gaudet, Dillon E.; Gallotto, Sara L.; Weyman, Elizabeth A.; MacDonald, Shannon M.; Ebb, David H.; Huang, Mary; Friedmann, Allison M.; Jones, Robin M.; Tarbell, Nancy J.; Kuhlthau, Karen A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA RO-21 BP 163 EP 163 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000657 ER PT J AU Plant, A Koyama, S Dranoff, G Kieran, M Ritz, J AF Plant, Ashley Koyama, Shohei Dranoff, Glenn Kieran, Mark Ritz, Jerome TI IMMUNOPHENOTYPING OF PEDIATRIC BRAIN TUMORS: CORRELATING IMMUNE INFILTRATE WITH HISTOLOGY, MUTATIONAL LOAD, AND SURVIVAL SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 12-15, 2016 CL Liverpool, ENGLAND C1 [Plant, Ashley; Koyama, Shohei; Dranoff, Glenn; Kieran, Mark; Ritz, Jerome] Dana Farber Canc Inst, Boston, MA 02115 USA. [Plant, Ashley; Kieran, Mark] Boston Childrens Hosp, Boston, MA USA. [Dranoff, Glenn] Novartis Inst Biomed Res, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2016 VL 18 SU 3 MA TB-03 BP 169 EP 169 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DR2QM UT WOS:000379749000679 ER PT J AU Baggett, TP Campbell, EG Chang, YC Magid, LM Rigotti, NA AF Baggett, Travis P. Campbell, Eric G. Chang, Yuchiao Magid, Leah M. Rigotti, Nancy A. TI Posttraumatic Stress Symptoms and Their Association With Smoking Outcome Expectancies Among Homeless Smokers in Boston SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID ADDICTION SEVERITY INDEX; SUBSTANCE USE DISORDERS; PTSD CHECKLIST PCL; TRAUMATIC BRAIN-INJURY; LOS-ANGELES-COUNTY; PSYCHOMETRIC PROPERTIES; HEALTH-CARE; CIGARETTE-SMOKING; ADULTS PREVALENCE; SCHIZOPHRENIA AB Introduction: Cigarette smoking and traumatic life experiences are each common among homeless adults, but the prevalence and correlates of posttraumatic stress disorder (PTSD) symptoms among homeless smokers are not known. We assessed symptoms of PTSD and their association with smoking outcome expectancies in a sample of homeless smokers in Boston. Methods: We used time-location sampling to conduct an in-person survey of homeless adult smokers using Boston Health Care for the Homeless Program clinical services. We assessed symptoms of PTSD with the PTSD Checklist-Civilian version and considered scores at least 14 as positive. We used the Smoking Effects Questionnaire to assess positive and negative smoking outcome expectancies. We modeled the associations between PTSD screening status and smoking expectancies using design-adjusted linear regression. Results: Eighty-six percent of eligible individuals participated (N = 306). Sixty-eight percent of participants screened positive for PTSD. Screen-positive respondents were younger (P=.001), more likely to report fair/poor health (P=.01), chronic obstructive pulmonary disease (P=.02), and past-month hallucinations (P=.004), and had greater drug (P<.001) and alcohol (P<.001) use severity and cigarette dependence (P=.002). In analyses controlling for these confounders, PTSD screen-positive participants more strongly endorsed smoking to reduce negative affect (P=.01), smoking for social benefits (P=.002), and smoking for weight control (P=.03). Exploratory analyses suggested that these associations were driven by avoidance/numbing and re-experiencing symptoms. Conclusions: Symptoms of posttraumatic stress are common among homeless smokers and strongly associated with positive smoking outcome expectancies. Tobacco cessation programs for this population should consider screening for PTSD and fostering a trauma-sensitive treatment environment. Implications: In this study of homeless cigarette smokers in Boston, over two-thirds of participants screened positive for PTSD. PTSD screen-positive respondents more strongly endorsed multiple positive smoking outcome expectancies than screen-negative individuals. These findings suggest that the psychological sequelae of trauma may be a pervasive but under-recognized factor impacting the persistence of smoking among homeless people. Tobacco cessation programs for this population should consider screening for PTSD, fostering a trauma-sensitive treatment environment, and incorporating strategies that have shown promise in smokers with PTSD. C1 [Baggett, Travis P.; Chang, Yuchiao; Rigotti, Nancy A.] Massachusetts Gen Hosp, Div Gen Internal Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. [Baggett, Travis P.; Campbell, Eric G.; Chang, Yuchiao; Rigotti, Nancy A.] Harvard Med Sch, Dept Med, Boston, MA USA. [Baggett, Travis P.] Boston Hlth Care Homeless Program, Boston, MA USA. [Campbell, Eric G.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. [Magid, Leah M.] Boston Univ, Coll Hlth & Rehabil Sci, Boston, MA 02215 USA. [Magid, Leah M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Baggett, TP (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM tbaggett@mgh.harvard.edu FU National Institute on Drug Abuse at the National Institutes of Health [K23DA034008] FX This study was funded by the National Institute on Drug Abuse at the National Institutes of Health under award number K23DA034008 to TPB. The funding agency had no role in any aspect of this study. The study content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 56 TC 0 Z9 0 U1 4 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD JUN PY 2016 VL 18 IS 6 BP 1526 EP 1532 DI 10.1093/ntr/ntv238 PG 7 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA DR3TU UT WOS:000379826300019 PM 26508393 ER PT J AU Imran, TF Rahman, I Dikdan, S Shah, R Niazi, OT Thirunahari, N Alhaj, E Klapholz, M Gaziano, M Djousse, L AF Imran, Tasnim F. Rahman, Ifad Dikdan, Sean Shah, Rashesh Niazi, Osama T. Thirunahari, Nandan Alhaj, Eyad Klapholz, Marc Gaziano, Michael Djousse, Luc TI QT Prolongation and Clinical Outcomes in Patients with Takotsubo Cardiomyopathy SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE QT prolongation; stress-induced cardiomyopathy; takotsubo cardiomyopathy; transient left ventricular ballooning syndrome ID APICAL BALLOONING SYNDROME; TAKO-TSUBO CARDIOMYOPATHY; MYOCARDIAL-INFARCTION; ST-SEGMENT; DE-POINTES; ARRHYTHMIAS; FEATURES; INTERVAL AB Background: Takotsubo cardiomyopathy (TCM) has been associated with repolarization abnormalities including QT prolongation and acquired long QT syndrome. However, the association between QT prolongation and clinical outcomes in patients with TCM remains unclear. The aim of this study is to examine the association between QT prolongation and ventricular arrhythmias, cardiogenic shock, and death in patients with TCM. Methods: Forty-six patients with TCM met our inclusion criteria in an ongoing prospective cohort database from 2010 to May 2015. We assigned the patients to a long QT group or a normal QT group, and created a composite outcome consisting of ventricular arrhythmias, cardiogenic shock, or death. Results: The mean age of the participants was 59.7 +/- 16 years, 67% were women, and 63% had hypertension. Median follow-up time was 3.1 years (interquartile range: 2.0-3.8), with a total of 133.8 person-years. The mean left ventricular ejection fraction at diagnosis was 27.2% +/- 1.4%. The mean QTc on diagnosis was 484 ms +/- 10.2 ms for men, and 488 ms +/- 8.6 ms for women. The long QT group had a 4.1-times higher odds of having the composite clinical outcome as compared to the normal QT group (95% confidence interval: 1.1, 16.1, P = 0.04) after adjusting for age and race in logistic regression. Conclusion: Patients with TCM who have a long QT interval or develop acquired long QT syndrome due to TCM may be more likely to be intubated; require vasopressors; and develop shock, ventricular arrhythmias, and death than those with a normal QT interval. C1 [Imran, Tasnim F.; Gaziano, Michael; Djousse, Luc] Harvard Med Sch, Brigham & Womens Hosp, 1620 Tremont St, Boston, MA 02120 USA. [Imran, Tasnim F.; Gaziano, Michael; Djousse, Luc] Harvard Med Sch, VA Boston Healthcare Syst, Boston, MA USA. [Imran, Tasnim F.; Rahman, Ifad; Dikdan, Sean; Shah, Rashesh; Niazi, Osama T.; Thirunahari, Nandan; Alhaj, Eyad; Klapholz, Marc] Univ Med & Dent New Jersey, Newark, NJ USA. RP Imran, TF (reprint author), Harvard Med Sch, Brigham & Womens Hosp, 1620 Tremont St, Boston, MA 02120 USA. EM TFImran@partners.org RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 NR 16 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0147-8389 EI 1540-8159 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD JUN PY 2016 VL 39 IS 6 BP 607 EP 611 DI 10.1111/pace.12864 PG 5 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA DR5GL UT WOS:000379931400013 PM 27062153 ER PT J AU Balekian, DS Linnemann, RW Castro, VM Perlis, R Thadhani, R Camargo, CA AF Balekian, Diana S. Linnemann, Rachel W. Castro, Victor M. Perlis, Roy Thadhani, Ravi Camargo, Carlos A., Jr. TI Pre-birth cohort study of atopic dermatitis and severe bronchiolitis during infancy SO PEDIATRIC ALLERGY AND IMMUNOLOGY LA English DT Article DE asthma; atopic dermatitis; birth season; bronchiolitis; congenital heart disease; eczema; respiratory syncytial virus; risk factors ID RESPIRATORY SYNCYTIAL VIRUS; VITAMIN-D DEFICIENCY; RISK-FACTORS; UNITED-STATES; CHILDREN; ASTHMA; INFECTION; HOSPITALIZATION; MULTICENTER; ECZEMA AB Background: Infants hospitalized for bronchiolitis (i.e. severe bronchiolitis) are at increased risk of childhood asthma. There are many known risk factors for severe bronchiolitis, including cardiac and pulmonary diseases. Less is known about the association between atopic diseases and risk of severe bronchiolitis. We sought to further examine risk factors for severe bronchiolitis, focusing on atopic dermatitis (AD). Methods: We conducted a nested cohort study within the Massachusetts General Hospital Obstetric Maternal Study (MOMS), a prospective cohort of pregnant women enrolled during 1998-2006. Children of mothers enrolled in MOMS were included in the analysis if they received care within our health system (n = 5407). Potential risk factors for bronchiolitis and hospitalization data were extracted from the children's electronic health records; we also examined pregnancy and perinatal risk factors collected from the underlying MOMS data. Results: During the first year of life, 125 infants (2.3%) had severe bronchiolitis. Eighteen of these patients had AD; 11 (61%) were diagnosed with AD prior to bronchiolitis hospitalization. In unadjusted analyses, AD was associated with severe bronchiolitis (chi(2) 14.6; p < 0.001). In multivariable analyses adjusting for nine known risk factors for severe bronchiolitis, including demographics, birth season, disposition at birth, cardiac disease, maternal parity, and delivery mode, AD was associated with increased odds of severe bronchiolitis (odds ratio 2.72, 95% confidence interval 1.60-4.63). Conclusions: Atopic dermatitis is significantly associated with severe bronchiolitis in infancy. The mechanism of the AD-bronchiolitis association is unclear and merits further study; this research may shed light on the pathogenesis of asthma. C1 [Balekian, Diana S.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Balekian, Diana S.; Linnemann, Rachel W.; Thadhani, Ravi; Camargo, Carlos A., Jr.] Harvard Med Sch, Boston, MA USA. [Linnemann, Rachel W.] Massachusetts Gen Hosp, Dept Pediat, Div Pediat Pulmonol, Boston, MA 02114 USA. [Castro, Victor M.] Partners HealthCare Syst, Res Informat Syst & Comp, Boston, MA USA. [Castro, Victor M.] Massachusetts Gen Hosp, Dept Neurol, Comp Sci Lab, Boston, MA 02114 USA. [Perlis, Roy] Massachusetts Gen Hosp, Dept Psychiat, Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA. [Perlis, Roy] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, 125 Nashua St,Suite 920, Boston, MA 920 USA. EM ccamargo@partners.org FU National Institutes of Health [T32 HL116275] FX This work was supported by the National Institutes of Health (Grant T32 HL116275 to D.S.B.). NR 28 TC 2 Z9 2 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0905-6157 EI 1399-3038 J9 PEDIAT ALLERG IMM-UK JI Pediatr. Allergy Immunol. PD JUN PY 2016 VL 27 IS 4 BP 413 EP 418 DI 10.1111/pai.12532 PG 6 WC Allergy; Immunology; Pediatrics SC Allergy; Immunology; Pediatrics GA DR5FC UT WOS:000379927700012 PM 26766307 ER PT J AU Choi, J Shooshtari, P Samocha, KE Daly, MJ Cotsapas, C AF Choi, Jinmyung Shooshtari, Parisa Samocha, Kaitlin E. Daly, Mark J. Cotsapas, Chris TI Network Analysis of Genome-Wide Selective Constraint Reveals a Gene Network Active in Early Fetal Brain Intolerant of Mutation SO PLOS GENETICS LA English DT Article ID AUTISM SPECTRUM DISORDERS; DE-NOVO MUTATIONS; POSITIVE SELECTION; COMPLEX TRAITS; COMMON SNPS; ADAPTATION; FRAMEWORK; PROFILES; INSIGHTS; DISEASE AB Using robust, integrated analysis of multiple genomic datasets, we show that genes depleted for non-synonymous de novo mutations form a subnetwork of 72 members under strong selective constraint. We further show this subnetwork is preferentially expressed in the early development of the human hippocampus and is enriched for genes mutated in neurological Mendelian disorders. We thus conclude that carefully orchestrated developmental processes are under strong constraint in early brain development, and perturbations caused by mutation have adverse outcomes subject to strong purifying selection. Our findings demonstrate that selective forces can act on groups of genes involved in the same process, supporting the notion that purifying selection can act coordinately on multiple genes. Our approach provides a statistically robust, interpretable way to identify the tissues and developmental times where groups of disease genes are active. C1 [Choi, Jinmyung; Shooshtari, Parisa; Cotsapas, Chris] Yale Sch Med, Dept Neurol, New Haven, CT 06510 USA. [Samocha, Kaitlin E.; Daly, Mark J.; Cotsapas, Chris] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Samocha, Kaitlin E.; Daly, Mark J.; Cotsapas, Chris] Harvard Med Sch, Boston, MA 02115 USA. [Samocha, Kaitlin E.; Daly, Mark J.; Cotsapas, Chris] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Samocha, Kaitlin E.; Daly, Mark J.; Cotsapas, Chris] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Samocha, Kaitlin E.] Harvard Med Sch, Program Genet & Genom Biol & Biomed Sci, Boston, MA USA. [Cotsapas, Chris] Yale Sch Med, Dept Genet, New Haven, CT 06510 USA. RP Cotsapas, C (reprint author), Yale Sch Med, Dept Neurol, New Haven, CT 06510 USA.; Cotsapas, C (reprint author), Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.; Cotsapas, C (reprint author), Harvard Med Sch, Boston, MA 02115 USA.; Cotsapas, C (reprint author), Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA.; Cotsapas, C (reprint author), Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.; Cotsapas, C (reprint author), Yale Sch Med, Dept Genet, New Haven, CT 06510 USA. EM cotsapas@broadinstitute.org OI Cotsapas, Chris/0000-0002-7772-5910 NR 36 TC 2 Z9 2 U1 1 U2 1 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 JUN PY 2016 VL 12 IS 6 AR e1006121 DI 10.1371/journal.pgen.1006121 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA DQ6WS UT WOS:000379347100036 PM 27305007 ER PT J AU Roffman, JL Tanner, AS Eryilmaz, H Rodriguez-Thompson, A Silverstein, NJ Ho, NF Nitenson, AZ Chonde, DB Greve, DN Abi-Dargham, A Buckner, RL Manoach, DS Rosen, BR Hooker, JM Catana, C AF Roffman, Joshua L. Tanner, Alexandra S. Eryilmaz, Hamdi Rodriguez-Thompson, Anais Silverstein, Noah J. Ho, New Fei Nitenson, Adam Z. Chonde, Daniel B. Greve, Douglas N. Abi-Dargham, Anissa Buckner, Randy L. Manoach, Dara S. Rosen, Bruce R. Hooker, Jacob M. Catana, Ciprian TI Dopamine D-1 signaling organizes network dynamics underlying working memory SO SCIENCE ADVANCES LA English DT Article ID INTRINSIC FUNCTIONAL CONNECTIVITY; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; D1 RECEPTOR-BINDING; PREFRONTAL CORTEX; CORTICAL SURFACE; HUMAN BRAIN; GRAPHICAL ANALYSIS; COORDINATE SYSTEM; PET AB Local prefrontal dopamine signaling supports working memory by tuning pyramidal neurons to task-relevant stimuli. Enabled by simultaneous positron emission tomography-magnetic resonance imaging (PET-MRI), we determined whether neuromodulatory effects of dopamine scale to the level of cortical networks and coordinate their interplay during working memory. Among network territories, mean cortical D-1 receptor densities differed substantially but were strongly interrelated, suggesting cross-network regulation. Indeed, mean cortical D-1 density predicted working memory-emergent decoupling of the frontoparietal and default networks, which respectively manage task-related and internal stimuli. In contrast, striatal D-1 predicted opposing effects within these two networks but no between-network effects. These findings specifically link cortical dopamine signaling to network crosstalk that redirects cognitive resources to working memory, echoing neuromodulatory effects of D-1 signaling on the level of cortical microcircuits. C1 [Roffman, Joshua L.; Tanner, Alexandra S.; Eryilmaz, Hamdi; Rodriguez-Thompson, Anais; Silverstein, Noah J.; Ho, New Fei; Nitenson, Adam Z.; Buckner, Randy L.; Manoach, Dara S.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St, Boston, MA 02114 USA. [Roffman, Joshua L.; Chonde, Daniel B.; Greve, Douglas N.; Buckner, Randy L.; Manoach, Dara S.; Rosen, Bruce R.; Hooker, Jacob M.; Catana, Ciprian] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. [Abi-Dargham, Anissa] Columbia Univ, Dept Psychiat, Med Ctr, Harkness Pavilion,180 Ft Washington Ave, New York, NY 10032 USA. RP Roffman, JL (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St, Boston, MA 02114 USA.; Roffman, JL (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM jroffman@partners.org FU NCRR NIH HHS [S10 RR017208, S10 RR019933, S10 RR022976, S10 RR023385, S10 RR023401, S10 RR026666]; NIBIB NIH HHS [P41 EB015896, R21 EB018964]; NIMH NIH HHS [K23 MH084059, R01 MH101425]; NINDS NIH HHS [R01 NS083534] NR 58 TC 0 Z9 0 U1 2 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 2375-2548 J9 SCI ADV JI Sci. Adv. PD JUN PY 2016 VL 2 IS 6 AR UNSP e1501672 DI 10.1126/sciadv.1501672 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DR7IS UT WOS:000380073800008 PM 27386561 ER PT J AU Miloslavsky, EM Criscione-Schreiber, LG Jonas, BL O'Rourke, KS McSparron, JI Bolster, MB AF Miloslavsky, Eli M. Criscione-Schreiber, Lisa G. Jonas, Beth L. O'Rourke, Kenneth S. McSparron, Jakob I. Bolster, Marcy B. TI Fellow As Teacher Curriculum: Improving Rheumatology Fellows' Teaching Skills During Inpatient Consultation SO ARTHRITIS CARE & RESEARCH LA English DT Article ID RESIDENTS; PROGRAMS AB Objective. Enhancing rheumatology fellows' teaching skills in the setting of inpatient consultation may have a broad positive impact. Such efforts may improve fellows' clinical skills and overall patient care. Most importantly, effective resident-fellow teaching interactions may not only increase residents' knowledge of rheumatology but may influence their career choice. however, a number of barriers to the resident-fellow teaching interaction have been identified, including fellows' teaching skills. We developed the Fellow As Clinical Teacher (FACT) curriculum in order to enhance fellows' teaching skills during inpatient consultation. Methods. The FACT curriculum was delivered in two 45-minute workshops during the 3-day Winter Symposium of the Carolinas Fellows Collaborative. We evaluated its effect with self-assessment surveys and fellow performance on the objective structured teaching exercise (OSTE) before and after participation in the curriculum. Results. Nineteen fellows from 4 rheumatology training programs participated in the pre- and post-curriculum OSTEs and 18 fellows completed pre- and post-curriculum surveys. OSTE scores improved on 5 of the 8 items assessed, and the total OSTE score improved as well (34.7 versus 29.5; P < 0.01) after the FACT curriculum. Fellows' self assessment of their teaching skills and intent to teach during consultation also increased after participation in the curriculum. Conclusion. The FACT curriculum, focused on teaching during consultation, improved fellows' teaching skills and attitudes toward teaching. Improving and increasing fellow teaching, particularly in the consultation setting, may impact patient care, resident and fellow learning, and teaching skills of future faculty, and could potentially influence residents' career choice. C1 [Miloslavsky, Eli M.; Bolster, Marcy B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Criscione-Schreiber, Lisa G.] Duke Univ, Sch Med, Durham, NC USA. [Jonas, Beth L.] Univ N Carolina, Chapel Hill, NC USA. [Jonas, Beth L.] Thurston Arthrit Res Ctr, Chapel Hill, NC USA. [O'Rourke, Kenneth S.] Wake Forest Sch Med, Winston Salem, NC USA. [McSparron, Jakob I.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Miloslavsky, EM (reprint author), Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, 55 Fruit St,Suite 2C, Boston, MA 02114 USA. EM emiloslavsky@mgh.harvard.edu FU Rheumatology Research Foundation FX Dr. Miloslavsky's work was supported by the Rheumatology Research Foundation Clinician Scholar Educator Award. NR 15 TC 1 Z9 1 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD JUN PY 2016 VL 68 IS 6 BP 877 EP 881 DI 10.1002/acr.22733 PG 5 WC Rheumatology SC Rheumatology GA DR1ON UT WOS:000379674900020 PM 26414763 ER PT J AU Ward, MM Deodhar, A Reveille, JD Caplan, L AF Ward, Michael M. Deodhar, Atul Reveille, John D. Caplan, Liron TI Treatment of patients with nonradiographic axial spondyloarthritis who have negative magnetic resonance imaging results and normal C-reactive protein levels at baseline: comment on the article by Ward et al Reply SO ARTHRITIS CARE & RESEARCH LA English DT Letter ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; EFFICACY; SACROILIITIS; ADALIMUMAB C1 [Ward, Michael M.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Deodhar, Atul] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Reveille, John D.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Caplan, Liron] Denver Vet Affairs Med Ctr, Aurora, CO USA. [Caplan, Liron] Univ Colorado, Aurora, CO USA. RP Ward, MM (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 AR041153-04] 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 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD JUN PY 2016 VL 68 IS 6 BP 886 EP 887 DI 10.1002/acr.22878 PG 3 WC Rheumatology SC Rheumatology GA DR1ON UT WOS:000379674900023 PM 26990665 ER PT J AU Di Meglio, A Freedman, RA Lin, NU Barry, WT Metzger, O Keating, NL King, TA Sertoli, MR Boccardo, F Winer, EP Vaz-Luis, I AF Di Meglio, Antonio Freedman, Rachel A. Lin, Nancy U. Barry, William T. Metzger-Filho, Otto Keating, Nancy L. King, Tari A. Sertoli, Mario Roberto Boccardo, Francesco Winer, Eric P. Vaz-Luis, Ines TI Time trends in incidence rates and survival of newly diagnosed stage IV breast cancer by tumor histology: a population-based analysis SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Metastatic breast cancer; Incidence; Survival; Invasive ductal carcinoma; Invasive lobular carcinoma ID INVASIVE LOBULAR CARCINOMA; METASTATIC BREAST; UNITED-STATES; WOMEN; SUBTYPE; DECADES; PERIOD AB Few contemporary data are available that compare incidence and survival of metastatic breast cancer between ductal and lobular carcinomas. Using the Surveillance, Epidemiology, and End Results-9 registries, we identified 10,639 patients with de novo metastatic breast cancer diagnosed from 1990 to 2011. Annual age-adjusted incidence rates and annual percent changes (APCs) were analyzed. Multivariable Cox regression models were used to investigate the impact of year of diagnosis and histology on overall survival. 9250 (86.9 %) patients had ductal and 1389 (13.1 %) had lobular carcinomas. Metastatic breast cancer incidence increased slightly over time for ductal (APC = +1.7, 95 % confidence interval (CI) = +1.0 to +2.4) and lobular carcinomas (APC = +3.0, 95 % CI = +1.8 to +4.3). Median overall survival was 22 months among the whole cohort. More recent year of diagnosis was associated with better overall survival only for patients with ductal carcinomas (interaction p value = 0.006), with an adjusted hazard ratio of death for every five-year increment in the date of diagnosis of 0.93 (95 % CI = 0.91-0.95) among ductal carcinomas, compared with 1.05 (95 % CI = 0.95-1.10) among lobular carcinomas. Overall survival was longer for lobular versus ductal carcinomas (28 versus 21 months, respectively; adjusted hazard ratio of death = 0.93, 95 % CI = 0.87-0.99), but the magnitude of this effect was attenuated among the cohort restricted to hormone receptor-positive tumors. In this population-based analysis, incidence rates of metastatic breast cancer at presentation increased slightly over time for both histologies, and particularly for lobular tumors. A modest improvement in metastatic breast cancer median overall survival was observed, but was apparently limited to ductal carcinomas. C1 [Di Meglio, Antonio; Freedman, Rachel A.; Lin, Nancy U.; Metzger-Filho, Otto; Winer, Eric P.; Vaz-Luis, Ines] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. [Di Meglio, Antonio; Sertoli, Mario Roberto; Boccardo, Francesco] IRCCS AOU San Martino Univ Hosp, IST Natl Canc Res Inst, Acad Unit Med Oncol, Genoa, Italy. [Barry, William T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02215 USA. [Keating, Nancy L.] Harvard Med Sch, Dept Hlth Care Policy, Boston, MA USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA. [King, Tari A.] Brigham & Womens Hosp, Dept Surg Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. RP Vaz-Luis, I (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM InesV_Luis@dfci.harvard.edu FU Fundacao para a Ciencia e Tecnologia [HMSP-ICS/0004/2011]; Dana-Farber Cancer Institute Friends Grant FX This study used the Surveillance, Epidemiology, and End Results (SEER) database. The interpretation and reporting of these data are the sole responsibility of the authors. We thank Joyce Lii for her programming expertise, and the SEER*Stat Technical Support Team for their help with the incidence data used for the present study. The study was supported by Fundacao para a Ciencia e Tecnologia (HMSP-ICS/0004/2011, Career Development Award) (to Ines Vaz-Luis) and Dana-Farber Cancer Institute Friends Grant (to Ines Vaz-Luis). NR 30 TC 1 Z9 1 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2016 VL 157 IS 3 BP 587 EP 596 DI 10.1007/s10549-016-3845-5 PG 10 WC Oncology SC Oncology GA DQ8XQ UT WOS:000379495400018 PM 27271765 ER PT J AU Kenney, PA Nawaf, CB Mustafa, M Wen, SJ Wszolek, MF Pettaway, CA Ward, JF Davis, JW Pisters, LL AF Kenney, Patrick A. Nawaf, Cayce B. Mustafa, Mahmoud Wen, Sijin Wszolek, Matthew F. Pettaway, Curtis A. Ward, John F. Davis, John W. Pisters, Louis L. TI Robotic-assisted laparoscopic versus open salvage radical prostatectomy following radiotherapy SO CANADIAN JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; radiotherapy; salvage therapy; prostatectomy ID ANDROGEN DEPRIVATION THERAPY; RETROPUBIC PROSTATECTOMY; SINGLE-INSTITUTION; RADIATION-THERAPY; CANCER; OUTCOMES; COMPLICATIONS; FAILURE; EXPERIENCE; MEN AB Introduction: To describe immediate perioperative outcomes of robot-assisted laparoscopic salvage radical prostatectomy for recurrent cancer following radiation therapy, and compare outcomes to a contemporary open surgical cohort. Materials and methods: A total of 39 patients underwent salvage radical prostatectomy with pelvic lymphadenectomy (20 robotic, 19 open) for local recurrence following radiation therapy at a single institution between 2007 and 2011. Intraoperative parameters, postoperative complications, and oncological outcomes, were recorded. Wilcoxon rank sum test and Fisher's exact test were used for comparison of continuous and categorical variables respectively. Mean values of numeric variables are reported with standard deviation. Results: The cohorts were similar with respect to age, ethnicity, and American Society of Anesthesiologists Score classification. Estimated blood loss was lower in the robotic group versus the open group (381.3 mL versus 865.0 mL, p = 0.001). There was no difference in the rate of intraoperative complications, postoperative Clavien >= 3 complications (30% versus 15.7%), anastomotic leak (40% versus 42.1%), or wound infection (0% versus 15.7%) in the robotic and open groups. Mean node yield (10.4 versus 11.8), positive surgical margins (15.0% versus 15.7%), and undetectable prostate-specific antigen rate (78% versus 60%) were also similar between the robotic and open groups. Conclusions: Robotic salvage prostatectomy appears to have no significant difference to the open approach with respect to safety and surgical quality as measured by complications, node yield and surgical margins in this retrospective single-institution series. C1 [Kenney, Patrick A.; Nawaf, Cayce B.] Yale Sch Med, Dept Urol, New Haven, CT USA. [Mustafa, Mahmoud] Najaj Univ, Sch Med, Dept Urol, Nablus, Israel. [Wen, Sijin] West Virginia Univ, Hlth Sci Ctr, Dept Biostat, Morgantown, WV 26506 USA. [Wszolek, Matthew F.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Pettaway, Curtis A.; Ward, John F.; Davis, John W.; Pisters, Louis L.] Univ Texas MD Anderson Canc Ctr, Dept Urol, 1515 Holcombe,Unit 1373, Houston, TX 77030 USA. RP Pisters, LL (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Urol, 1515 Holcombe,Unit 1373, Houston, TX 77030 USA. NR 21 TC 0 Z9 0 U1 2 U2 2 PU CANADIAN J UROLOGY PI ST LAURENT PA 2330 WARD ST, STE 604, ST LAURENT, QUEBEC H4M 2V6, CANADA SN 1195-9479 J9 CAN J UROL JI Can. J. Urol. PD JUN PY 2016 VL 23 IS 3 BP 8272 EP 8278 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA DR0ZO UT WOS:000379635800004 ER PT J AU Sadeghian, H Motiei-Langroudi, R AF Sadeghian, Homa Motiei-Langroudi, Rouzbeh TI Does distracting pain justify performing brain computed tomography in multiple traumas with mild head injury? SO EMERGENCY RADIOLOGY LA English DT Article DE Mild; Brain injury; Trauma; Distracting pain; Computed tomography ID RULE AB Traumatic brain injury (TBI) is a significant health concern classified as mild, moderate, and severe. Although the indications to perform brain computed tomography (CT) are clear in moderate and severe cases, there still exists controversy in mild TBI (mTBI). We designed the study to evaluate the significance of distracting pain in patients with mTBI. The study population included patients with mild traumatic brain injury (GCS a parts per thousand yen13). Moderate and high risk factors including age < 18 months or a parts per thousand yen60 years, moderate to severe or progressive headache, a parts per thousand yen2 episodes of vomiting, loss of consciousness (LOC), post-traumatic amnesia, seizure or prior antiepileptic use, alcohol intoxication, previous neurosurgical procedures, uncontrolled hypertension, anticoagulant use, presence of focal neurologic deficits, deformities in craniofacial region, and penetrating injuries were excluded. The patients were then grouped based on presence (DP+) or absence (DP-) of another organ fracture with severe pain (based on VAS). The primary outcome was any abnormal findings on brain CT scans; 330 patients were enrolled (184 DP+ and 146 DP-). Overall, two DP+ and one DP- patients had mild cerebral edema in brain CT (p > 0.99). No patients had any neurologic symptoms or signs in follow-up. Our results show that in the absence of any other risk factors, distracting pain from other organs (limbs, pelvis, and non-cervical spine) cannot be regarded as a brain CT indication in patients with mild TBI, as it is never associated with significant intracranial lesions. C1 [Sadeghian, Homa] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Neurovasc Res Lab, Charlestown, MA USA. [Motiei-Langroudi, Rouzbeh] Bam Univ Med Sci, Pastor Hosp, Div Neurosurg, Dept Surg, Bam, Iran. RP Motiei-Langroudi, R (reprint author), Bam Univ Med Sci, Pastor Hosp, Div Neurosurg, Dept Surg, Bam, Iran. EM r_motiei@yahoo.com NR 11 TC 0 Z9 1 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1070-3004 EI 1438-1435 J9 EMERG RADIOL JI Emerg. Radiol. PD JUN PY 2016 VL 23 IS 3 BP 241 EP 244 DI 10.1007/s10140-016-1387-0 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DR1BL UT WOS:000379640900006 PM 26931118 ER PT J AU Abel, GA Efficace, F Buckstein, RJ Tinsley, S Jurcic, JG Martins, Y Steensma, DP Watts, CD Raza, A Lee, SJ List, AF Klaassen, RJ AF Abel, Gregory A. Efficace, Fabio Buckstein, Rena J. Tinsley, Sara Jurcic, Joseph G. Martins, Yolanda Steensma, David. P. Watts, Corey D. Raza, Azra Lee, Stephanie J. List, Alan F. Klaassen, Robert J. TI Prospective international validation of the Quality of Life in Myelodysplasia Scale (QUALMS) SO HAEMATOLOGICA LA English DT Article ID TRANSFUSION-DEPENDENT PATIENTS; PATIENT-REPORTED OUTCOMES; PLACEBO-CONTROLLED TRIAL; ACUTE MYELOID-LEUKEMIA; RANDOMIZED PHASE-III; EUROPEAN-ORGANIZATION; POSTTRAUMATIC GROWTH; CELL TRANSPLANTATION; SYMPTOM ASSESSMENT; COLORECTAL-CANCER AB Disease-specific measures of quality of life can improve assessment of disease-related symptoms and psychosocial sequelae. We report on the development and validation of the Quality of Life in Myelodysplasia Scale (QUALMS), a 38-item assessment tool for patients with myelodysplastic syndromes (MDS). In 2014-2015, a multi-center cohort of patients with myelodysplasia completed the QUALMS, as well as the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and the Functional Assessment of Cancer Therapy Anemia Scale (FACT-An); a second administration was undertaken three to six months later. A total of 255 patients from the United States, Canada and Italy participated. Median age was 72 years, 56.1% were men, and the International Prognostic Scoring System distribution was 40.4% low, 42.0% intermediate-1, 13.3% intermediate-2 and 2.3% high. QUALMS scores ranged from 24 to 99 (higher scores are better), with a mean of 67.2 [standard deviation (SD)=15.2]. The measure was internally consistent (alpha=0.92), and moderately correlated with the multi-item QLQ-C30 scales and the FACT-An (r=-0.65 to 0.79; all P<0.001). Patients with hemoglobin of 8 g/dL or under scored lower than those with hemoglobin over 10 g/dL (61.8 vs. 71.1; P<0.001), and transfusion-dependent patients scored lower than transfusion-independent patients (62.4 vs. 69.7; P<0.01). Principal components analysis revealed "physical burden", "benefit-finding", and "emotional burden" subscales. There was good overall test-retest reliability among those with stable hemoglobin (r=0.81), and significant changes for patients hospitalized or with infections between administrations (both P<0.01). These data suggest the QUALMS is a valuable tool for assessing MDS-specific quality of life in the modern treatment era. C1 [Abel, Gregory A.; Martins, Yolanda; Watts, Corey D.] Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Boston, MA 02115 USA. [Abel, Gregory A.; Steensma, David. P.] Dana Farber Canc Inst, Ctr Leukaemia, Dept Med Oncol, Boston, MA 02115 USA. [Efficace, Fabio] Italian Grp Adult Hematol Dis GIMEMA, Ctr Data, Rome, Italy. [Efficace, Fabio] Italian Grp Adult Hematol Dis GIMEMA, Hlth Outcomes Res Unit, Rome, Italy. [Buckstein, Rena J.] Odette Canc & Sunnybrook Hlth Sci Ctr, Dept Med Hematol Oncol, Toronto, ON, Canada. [Tinsley, Sara; List, Alan F.] H Lee Moffitt Canc Ctr & Res Inst, Dept Malignant Hematol, Tampa, FL USA. [Jurcic, Joseph G.; Raza, Azra] Columbia Univ, Dept Med, Div Hematol Oncol, Med Ctr, New York, NY USA. [Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA. [Klaassen, Robert J.] Childrens Hosp Eastern Ontario, Dept Pediat, Ottawa, ON, Canada. RP Abel, GA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Boston, MA 02115 USA.; Abel, GA (reprint author), Dana Farber Canc Inst, Ctr Leukaemia, Dept Med Oncol, Boston, MA 02115 USA. EM gregory_abel@dfci.harvard.edu FU Aplastic Anemia and MDS International Foundation grant; Leukemia and Lymphoma Society Clinical Scholar Award; Canadian Cancer Society [701837] FX We are grateful for funding from an Aplastic Anemia and MDS International Foundation grant, a Leukemia and Lymphoma Society Clinical Scholar Award, and a quality of life Grant of the Canadian Cancer Society in memory of James Tyrell (grant # 701837). NR 40 TC 0 Z9 0 U1 3 U2 4 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 IS 6 BP 781 EP 788 DI 10.3324/haematol.2015.140335 PG 8 WC Hematology SC Hematology GA DQ8OV UT WOS:000379471900034 PM 26944474 ER PT J AU Li, HJ Shi, JH Huang, NJ Pishesha, N Natarajan, A Eng, JC Lodish, HF AF Li, Hojun Shi, Jiahai Huang, Nai-Jia Pishesha, Novalia Natarajan, Anirudh Eng, Jennifer C. Lodish, Harvey F. TI Efficient CRISPR-Cas9 mediated gene disruption in primary erythroid progenitor cells SO HAEMATOLOGICA LA English DT Letter DE hematopoiesis; red cells; genome editing ID ERYTHROPOIESIS; DIFFERENTIATION; INDUCTION; PROTEINS; ANEMIA C1 [Li, Hojun; Shi, Jiahai; Huang, Nai-Jia; Pishesha, Novalia; Natarajan, Anirudh; Eng, Jennifer C.; Lodish, Harvey F.] Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. [Li, Hojun] Harvard Med Sch, Dept Pediat, Boston, MA USA. [Li, Hojun] Boston Childrens Hosp, Div Hematol & Oncol, Boston, MA USA. [Li, Hojun] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Pishesha, Novalia; Lodish, Harvey F.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Pishesha, Novalia; Lodish, Harvey F.] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RP Lodish, HF (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.; Lodish, HF (reprint author), MIT, Dept Biol, Cambridge, MA 02139 USA.; Lodish, HF (reprint author), MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM lodish@wi.mit.edu RI shi, jiahai/D-7650-2013 OI shi, jiahai/0000-0002-6467-8289 FU NHLBI NIH HHS [P01 HL032262, T32 HL007574]; NIDDK NIH HHS [R01 DK068348] NR 15 TC 1 Z9 1 U1 0 U2 5 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 IS 6 BP E216 EP E219 DI 10.3324/haematol.2015.135723 PG 4 WC Hematology SC Hematology GA DQ8OV UT WOS:000379471900001 PM 26969085 ER PT J AU Nazha, A Komrokji, RS Garcia-Manero, G Barnard, J Roboz, GJ Steensma, DP DeZern, AE Zell, K Zimmerman, C Al Ali, N Jabbour, E Greenberg, MD Kantarjian, HM Maciejewski, JP List, AF Sekeres, MA AF Nazha, Aziz Komrokji, Rami S. Garcia-Manero, Guillermo Barnard, John Roboz, Gail J. Steensma, David P. DeZern, Amy E. Zell, Katrina Zimmerman, Cassie Al Ali, Najla Jabbour, Elias Greenberg, Molly D. Kantarjian, Hagop M. Maciejewski, Jaroslaw P. List, Alan F. Sekeres, Mikkael A. CA MDS Clin Res Consortium TI The efficacy of current prognostic models in predicting outcome of patients with myelodysplastic syndromes at the time of hypomethylating agent failure SO HAEMATOLOGICA LA English DT Letter DE MDS; hypomethylating agent; prognostic models ID SCORING SYSTEM; CLASSIFICATION; AZACITIDINE; PROPOSAL C1 [Nazha, Aziz; Zimmerman, Cassie; Maciejewski, Jaroslaw P.; Sekeres, Mikkael A.] Cleveland Clin, Leukemia Program, Cleveland, OH 44106 USA. [Nazha, Aziz; Zimmerman, Cassie; Maciejewski, Jaroslaw P.; Sekeres, Mikkael A.] Cleveland Clin, Dept Translat Hematol & Oncol Res, Cleveland, OH 44106 USA. [Komrokji, Rami S.; Al Ali, Najla; List, Alan F.] H Lee Moffitt Canc Ctr & Res Inst, Dept Malignant Hematol, Tampa, FL USA. [Garcia-Manero, Guillermo; Jabbour, Elias; Kantarjian, Hagop M.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Barnard, John; Zell, Katrina] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA. [Roboz, Gail J.; Greenberg, Molly D.] New York Presbyterian Hosp, Weill Cornell Med Coll, Div Hematol & Oncol, New York, NY USA. [Steensma, David P.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [DeZern, Amy E.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Sekeres, MA (reprint author), Cleveland Clin, Leukemia Program, Cleveland, OH 44106 USA.; Sekeres, MA (reprint author), Cleveland Clin, Dept Translat Hematol & Oncol Res, Cleveland, OH 44106 USA. EM sekerem@ccf.org FU NCI NIH HHS [P30 CA016672] NR 13 TC 2 Z9 2 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2016 VL 101 IS 6 BP E224 EP E227 DI 10.3324/haematol.2015.140962 PG 4 WC Hematology SC Hematology GA DQ8OV UT WOS:000379471900003 PM 26992944 ER PT J AU Villani, V Bohnen, JD Torabi, R Sabbatino, F Chang, DC Ferrone, CR AF Villani, Vincenzo Bohnen, Jordan D. Torabi, Radbeh Sabbatino, Francesco Chang, David C. Ferrone, Cristina R. TI "Idealized" vs. "True" learning curves: the case of laparoscopic liver resection SO HPB LA English DT Article ID HEPATOCELLULAR-CARCINOMA; CANINE MODEL; OUTCOMES; FEASIBILITY; EXPERIENCE AB Background: Learning curves are believed to resemble an "idealized" model, in which continuous improvement occurs until a plateau is reached. We hypothesized that this "idealized" model would not adequately describe the learning process for a complex surgical technique, specifically laparoscopic liver resection (LLR). Methods: We analyzed the first 150 LLRs performed by a surgeon with expertise in hepatobiliary/laparoscopic surgery but with no previous LLR experience. We divided the procedures performed in 5 consecutive groups of 30 procedures, then compared groups in terms of complications, operative time, length of stay, and estimated blood loss. Results: We observed an increase in operative complexity (3.3% major operations in Group 1 vs. 23.3% in Group 5, p = 0.05). Complications decreased from Group 1 to Group 2 (20%-3%), but increased again as more complex procedures were performed (3% in Group 2-13% in Group 5). Similar improvement/regression patterns were observed for operative time and EBL. Discussion: The "true" learning curve for LLR is more appropriately described as alternating periods of improvement and regression until mastery is achieved. Surgeons should understand the true learning curves of procedures they perform, recognizing and mitigating the increased risk they assume by taking on more complex procedures. C1 [Villani, Vincenzo; Bohnen, Jordan D.; Torabi, Radbeh; Sabbatino, Francesco; Chang, David C.; Ferrone, Cristina R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Chang, David C.] Massachusetts Gen Hosp, Codman Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. RP Ferrone, CR (reprint author), 15 Parkman St,Wang 460, Boston, MA 02114 USA. EM CFerrone@partners.org FU Centro per la Comunicazione e la Ricerca of the Collegio Ghislieri of Pavia FX Vincenzo Villani is the recipient of a Research Fellowship from the Centro per la Comunicazione e la Ricerca of the Collegio Ghislieri of Pavia. NR 31 TC 1 Z9 1 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1365-182X EI 1477-2574 J9 HPB JI HPB PD JUN PY 2016 VL 18 IS 6 BP 504 EP 509 DI 10.1016/j.hpb.2016.03.610 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA DR1AN UT WOS:000379638400003 PM 27317954 ER PT J AU Rudmik, L Soler, ZM Hopkins, C Schlosser, RJ Peters, A White, AA Orlandi, RR Fokkens, WJ Douglas, R Smith, TL AF Rudmik, Luke Soler, Zachary M. Hopkins, Claire Schlosser, Rodney J. Peters, Anju White, Andrew A. Orlandi, Richard R. Fokkens, Wytske J. Douglas, Richard Smith, Timothy L. TI Defining appropriateness criteria for endoscopic sinus surgery during management of uncomplicated adult chronic rhinosinusitis: a RAND/UCLA appropriateness study SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE chronic rhinosinusitis; sinusitis; patient selection; maximal medical therapy; appropriateness criteria; RAND; quality of health care; sinus surgery; surgery indications ID REFRACTORY CHRONIC RHINOSINUSITIS; CONTINUED MEDICAL THERAPY; SMALL-AREA VARIATION; COMPUTED-TOMOGRAPHY; UNITED-STATES; GEOGRAPHIC-VARIATION; SYMPTOM OUTCOMES; IMPACT OUTCOMES; NASAL POLYPOSIS; HEALTH-CARE AB BackgroundAppropriate indications for endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) are currently poorly defined. The lack of clear surgical indications for ESS likely contributes to the large geographic variation in surgical rates and contributes to reduced quality of care. The objective of this study was to define appropriateness criteria for ESS during management of adult patients with uncomplicated CRS. MethodsThe RAND/UCLA appropriateness methodology was performed. An international, multidisciplinary panel of 10 experts in CRS was formed and completed 2 rounds of a modified Delphi ranking process along with a face-to-face meeting. ResultsA total of 624 clinical scenarios were ranked, 312 scenarios each for CRS with and CRS without nasal polyps. For adult patients with uncomplicated CRS with nasal polyps, ESS can be appropriately offered when the CT Lund-Mackay score is 1 and there has been a minimum trial of a topical intranasal corticosteroid plus a short-course of systemic corticosteroid with a post-treatment total SNOT-22 score 20. For adult patients with uncomplicated CRS without nasal polyps, ESS can be appropriately offered when the CT Lund-Mackay score is 1 and there has been a minimum trial of a topical intranasal corticosteroid plus either a short-course of a broad spectrum/culture-directed systemic antibiotic or the use of a prolonged course of systemic low-dose anti-inflammatory antibiotic with a post-treatment total SNOT-22 score 20. ConclusionThis study has developed and reported of list of appropriateness criteria to offer ESS as a treatment option during management of uncomplicated adult CRS. The extent or technique of ESS was not addressed in this study and will depend on surgeon and patient factors. Furthermore, these criteria are the minimal threshold to make ESS a treatment option and do not imply that all patients meeting these criteria require surgery. The decision to perform ESS should be made after an informed patient makes a preference-sensitive decision to proceed with surgery. Applying these appropriateness criteria for ESS may optimize patient selection, reduce the incidence of unwarranted surgery, and assist clinicians in providing high-quality, patient-centered care to patients with CRS C1 [Rudmik, Luke] Univ Calgary, Div Otolaryngol Head & Neck Surg, Dept Surg, Calgary, AB, Canada. [Soler, Zachary M.] Med Univ South Carolina, Div Otolaryngol Head & Neck Surg, Div Rhinol & Sinus Surg, Charleston, SC USA. [Hopkins, Claire] Guys & St Thomas NHS Trust, Dept ENT, London, England. [Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Peters, Anju] Northwestern Univ, Div Allergy, Dept Internal Med, Chicago, IL 60611 USA. [White, Andrew A.] Scripps Clin, Div Allergy & Immunol, La Jolla, CA 92037 USA. [Orlandi, Richard R.] Univ Utah, Div Otolaryngol Head & Neck Surg, Salt Lake City, UT USA. [Fokkens, Wytske J.] Acad Med Ctr, Dept Otorhinolaryngol, Amsterdam, Netherlands. [Douglas, Richard] Univ Auckland, Dept Surg, Auckland, New Zealand. [Smith, Timothy L.] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Div Rhinol & Sinus Surg, Oregon Sinus Ctr, Portland, OR 97201 USA. RP Rudmik, L (reprint author), Univ Calgary, Richmond Rd Diagnost & Treatment Ctr, Div Otolaryngol Head & Neck Surg, Dept Surg, 1820 Richmond Rd SW, Calgary, AB T2T 5C7, Canada. EM Lukerudmik@gmail.com NR 71 TC 6 Z9 6 U1 1 U2 1 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 JUN PY 2016 VL 6 IS 6 BP 557 EP 567 DI 10.1002/alr.21769 PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA DR1YL UT WOS:000379700700002 PM 26970538 ER PT J AU Scangas, GA Su, BM Remenschneider, AK Shrime, MG Metson, R AF Scangas, George A. Su, Brooke M. Remenschneider, Aaron K. Shrime, Mark G. Metson, Ralph TI Cost utility analysis of endoscopic sinus surgery for chronic rhinosinusitis SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE chronic sinusitis; health utility; cost effectiveness; endoscopic sinus surgery; disease severity; evidence-based medicine; health care economics; patient reported outcomes; quality of life ID WILLINGNESS-TO-PAY; ADJUSTED LIFE YEAR; ASYMPTOMATIC PRIMARY HYPERPARATHYROIDISM; CLINICAL-PRACTICE GUIDELINE; EXPENDITURE PANEL SURVEY; ECONOMIC-EVALUATION; HEALTH STATES; UNITED-STATES; CARE; COMPLICATIONS AB BackgroundThe purpose of this work was to evaluate the cost-effectiveness of endoscopic sinus surgery (ESS) compared to medical therapy for patients with chronic rhinosinusitis (CRS). MethodsThe study design consisted of a microsimulation Markov decision-tree economic model with a 31-year time horizon. A cohort of 489 patients who underwent ESS for CRS were matched 1 to 1 with a cohort of 489 patients from the national Medical Expenditures Panel Survey database who underwent medical management for CRS. Utility scores were calculated from responses to the EuroQol 5-Dimension instrument in both cohorts. Decision-tree analysis and a subsequent 10-state Markov model utilized published event probabilities as well as primary data from a large multisurgeon prospective outcomes study to calculate long-term costs and utility. The primary outcome measure was incremental cost per quality-adjusted life year (QALY). Multiple sensitivity analyses were performed. ResultsThe incremental cost-effectiveness ratio (ICER) for ESS vs medical therapy alone was $13,851.26 per QALY. The cost effectiveness acceptability curve demonstrated 85.84% and 98.69% certainty that the ESS strategy was the most cost-effective option at willingness-to-pay thresholds of $25,000 and $50,000 per QALY, respectively. ConclusionThis study shows ESS to be a cost-effective intervention compared to medical therapy alone for the management of patients with CRS. C1 [Scangas, George A.; Remenschneider, Aaron K.; Shrime, Mark G.; Metson, Ralph] Harvard Med Sch, Dept Otol & Laryngol, Boston, MA USA. [Scangas, George A.; Remenschneider, Aaron K.; Shrime, Mark G.; Metson, Ralph] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. [Su, Brooke M.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Shrime, Mark G.] Harvard Med Sch, Program Global Surg & Social Change, Boston, MA USA. RP Scangas, GA (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM George_Scangas@meei.harvard.edu FU Board Committee on Quality at Massachusetts Eye and Ear Infirmary FX Board Committee on Quality at Massachusetts Eye and Ear Infirmary. NR 70 TC 3 Z9 3 U1 0 U2 0 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 JUN PY 2016 VL 6 IS 6 BP 582 EP 589 DI 10.1002/alr.21697 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA DR1YL UT WOS:000379700700005 PM 26991813 ER PT J AU Carroll, WW Schlosser, RJ O'Connell, BP Soler, ZM Mulligan, JK AF Carroll, William W. Schlosser, Rodney J. O'Connell, Brendan P. Soler, Zachary M. Mulligan, Jennifer K. TI Vitamin D deficiency is associated with increased human sinonasal fibroblast proliferation in chronic rhinosinusitis with nasal polyps SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE chronic rhinosinusitis; endoscopic sinus surgery; fibroblast; vitamin D; nasal polyps ID DENDRITIC CELLS; MESENCHYMAL TRANSITION; EXPRESSION; MATRIX-METALLOPROTEINASE-9; INFLAMMATION; INDUCTION; SINUSITIS; EXPOSURE; RECEPTOR; ANALOGS AB BackgroundVitamin D3 (VD3) is a steroid hormone with known antiproliferative properties. Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have been shown to be VD3-deficient. Moreover, VD3 deficiency is associated with worse disease in patients with CRSwNP. One cell type thought to play a role in chronic rhinosinusitis (CRS) is the human sinonasal fibroblast (HSNF). The aim of this study was to investigate VD3 deficiency and HSNF proliferation in CRSwNP. MethodsBlood and sinus tissue explants were collected at the time of surgery from patients with CRSwNP (n = 15). Control subjects (n = 12) were undergoing surgery for cerebrospinal fluid leak repair or to remove non-hormone-secreting pituitary tumors. Ex vivo HSNF proliferation was analyzed with flow cytometry using expression of fibroblast-specific protein (FSP) and the proliferation marker Ki67. Plasma levels of 25-hydroxyvitamin D3 (25VD3) were measured by enzyme-linked immunosorbent assay. In vitro analysis of HSNF proliferation after treatment with calcitriol (1,25VD3) was performed using carboxyfluorescein succinimidyl ester (CFSE) and analyzed with flow cytometry. ResultsIn CRSwNP patients there was an inverse correlation between 25VD3 and proliferating HSNFs (p = 0.0135). This correlation was not seen for control patients (p = 0.3869). In vitro analysis showed that HSNFs from patients with CRSwNP had a higher proliferation index at baseline than HSNFs from control patients (p < 0.01). When treated with 1,25VD3, there was a significant decrease in HSNF proliferation index in patients with CRSwNP (p < 0.01), but not control patients. ConclusionVD3 deficiency is associated with increased HSNF proliferation in CRSwNP. Further investigation into how HSNFs and VD3 impact CRSwNP pathophysiology is warranted. C1 [Carroll, William W.; Schlosser, Rodney J.; O'Connell, Brendan P.; Soler, Zachary M.; Mulligan, Jennifer K.] Med Univ South Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC USA. [Schlosser, Rodney J.; Mulligan, Jennifer K.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Mulligan, Jennifer K.] Med Univ South Carolina, Dept Pediat, Charleston, SC USA. RP Mulligan, JK (reprint author), 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA. EM konopa@musc.edu FU American Academy of Otolaryngology-Head and Neck Surgery; Flight Attendant Medical Research Institute [092401, 113039]; Department of Veterans Affairs, Veterans Health Administration, Clinical Sciences Research and Development Merit Award [CSRD 1I01CX000377-01A2] FX American Academy of Otolaryngology-Head and Neck Surgery (to W.W.C.); Flight Attendant Medical Research Institute (092401 to J.K.M.; 113039 to R.J.S.); Department of Veterans Affairs, Veterans Health Administration, Clinical Sciences Research and Development Merit Award (CSRD 1I01CX000377-01A2 to R.J.S.). NR 35 TC 0 Z9 0 U1 1 U2 2 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 JUN PY 2016 VL 6 IS 6 BP 605 EP 610 DI 10.1002/alr.21704 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA DR1YL UT WOS:000379700700008 PM 26750566 ER PT J AU Holbrook, EH Rebeiz, L Schwob, JE AF Holbrook, Eric H. Rebeiz, Lina Schwob, James E. TI Office-based olfactory mucosa biopsies SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Rhinologic-Society (ARS) during the Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery (AAO-HNS) CY SEP 25-26, 2015 CL Dallas, TX SP Amer Rhinol Soc, Amer Acad Otolaryngol Head & Neck Surg DE olfactory epithelium; olfactory fila; humans; immunohistochemistry; S100; intermediate filaments; p75 neurotrophin receptor; olfactory ensheathing cells ID ENSHEATHING CELLS; TRAUMATIC ANOSMIA; SENSORY NEURONS; NERVE REPAIR; STEM-CELLS; EPITHELIUM; TISSUE; ABNORMALITIES; NEUROGENESIS; SELECTIVITY AB BackgroundRequests from researchers for olfactory mucosal biopsies are increasing as a result of advances in the fields of neuroscience and stem cell biology. Published studies report variable rates of success in obtaining true olfactory tissue, often below 50%. In cases where biopsies are not obtained carefully and confirmed through histological techniques, erroneous conclusions are made. Attention to the epithelium alone without submucosal analysis may add to the confusion. A consistent biopsy technique can help rhinologists obtain higher yields of olfactory mucosa. Confirmatory tissue staining analysis assures olfactory mucosa has been obtained, thereby strengthening clinical correlations and scientific conclusions. MethodsBiopsies of the septum within the anterior olfactory cleft were obtained under endoscopic guidance in an office procedure room using topical local anesthetic (lidocaine). After mucosal incision, a small, cupped, biopsy forceps was used to obtain specimens approximately 2 to 3 mm in size. Specimens were sectioned and analyzed with immunohistochemistry for presence of olfactory epithelium and/or olfactory fascicles. ResultsA total of 14 subjects were biopsied in this analysis. Four subjects had biopsies in the operating room (OR). The remaining 10 underwent biopsies in the clinic. All biopsies obtained in the OR revealed evidence of olfactory mucosa. Of the 10 clinic biopsies, 8 (80%) revealed evidence of olfactory mucosa. No complications were encountered. ConclusionHigh yields of olfactory mucosa can be obtained safely in an office-based setting. Technique, including attention to the area of biopsy, and confirmatory analysis are important in assuring presence of olfactory tissue. C1 [Holbrook, Eric H.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA USA. [Holbrook, Eric H.; Rebeiz, Lina; Schwob, James E.] Tufts Univ, Sch Med, Dept Dev Mol & Chem Biol, Boston, MA 02111 USA. RP Holbrook, EH (reprint author), 243 Charles St, Boston, MA 02114 USA. EM eric_holbrook@meei.harvard.edu FU NIDCD NIH HHS [R01 DC010242] NR 36 TC 0 Z9 0 U1 3 U2 3 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 JUN PY 2016 VL 6 IS 6 BP 646 EP 653 DI 10.1002/alr.21711 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA DR1YL UT WOS:000379700700014 PM 26833660 ER PT J AU Campbell, JP Ataer-Cansizoglu, E Bolon-Canedo, V Bozkurt, A Erdogmus, D Kalpathy-Cramer, J Patel, SN Reynolds, JD Horowitz, J Hutcheson, K Shapiro, M Repka, MX Ferrone, P Drenser, K Martinez-Castellanos, MA Ostmo, S Jonas, K Chan, RVP Chiang, MF AF Campbell, J. Peter Ataer-Cansizoglu, Esra Bolon-Canedo, Veronica Bozkurt, Alican Erdogmus, Deniz Kalpathy-Cramer, Jayashree Patel, Samir N. Reynolds, James D. Horowitz, Jason Hutcheson, Kelly Shapiro, Michael Repka, Michael X. Ferrone, Phillip Drenser, Kimberly Ana Martinez-Castellanos, Maria Ostmo, Susan Jonas, Karyn Chan, R. V. Paul Chiang, Michael F. CA Imaging Informatics Rop i-Rop Res TI Expert Diagnosis of Plus Disease in Retinopathy of Prematurity From Computer-Based Image Analysis SO JAMA OPHTHALMOLOGY LA English DT Article ID VASCULAR TORTUOSITY; ACCURACY; FELLOWS; OPHTHALMOLOGY; MULTICENTER; AGREEMENT; STANDARD; ROPTOOL; CARE; ROP AB IMPORTANCE Published definitions of plus disease in retinopathy of prematurity (ROP) reference arterial tortuosity and venous dilation within the posterior pole based on a standard published photograph. One possible explanation for limited interexpert reliability for a diagnosis of plus disease is that experts deviate from the published definitions. OBJECTIVE To identify vascular features used by experts for diagnosis of plus disease through quantitative image analysis. DESIGN, SETTING, AND PARTICIPANTS A computer-based image analysis system (Imaging and Informatics in ROP [i-ROP]) was developed using a set of 77 digital fundus images, and the system was designed to classify images compared with a reference standard diagnosis (RSD). System performance was analyzed as a function of the field of view (circular crops with a radius of 1-6 disc diameters) and vessel subtype (arteries only, veins only, or all vessels). Routine ROP screening was conducted from June 29, 2011, to October 14, 2014, in neonatal intensive care units at 8 academic institutions, with a subset of 73 images independently classified by 11 ROP experts for validation. The RSD was compared with the majority diagnosis of experts. MAIN OUTCOMES AND MEASURES The primary outcome measure was the percentage of accuracy of the i-ROP system classification of plus disease, with the RSD as a function of the field of view and vessel type. Secondary outcome measures included the accuracy of the 11 experts compared with the RSD. RESULTS Accuracy of plus disease diagnosis by the i-ROP computer-based system was highest (95%; 95% CI, 94%-95%) when it incorporated vascular tortuosity from both arteries and veins and with the widest field of view (6-disc diameter radius). Accuracy was 90% or less when using only arterial tortuosity and 85% or less using a 2-to 3-disc diameter view similar to the standard published photograph. Diagnostic accuracy of the i-ROP system (95%) was comparable to that of 11 expert physicians (mean 87%, range 79%-99%). CONCLUSIONS AND RELEVANCE Experts in ROP appear to consider findings from beyond the posterior retina when diagnosing plus disease and consider tortuosity of both arteries and veins, in contrast with published definitions. It is feasible for a computer-based image analysis system to perform comparably with ROP experts, using manually segmented images. C1 [Campbell, J. Peter; Ostmo, Susan; Chiang, Michael F.] Oregon Hlth & Sci Univ, Casey Eye Inst, Dept Ophthalmol, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA. [Ataer-Cansizoglu, Esra; Bozkurt, Alican; Erdogmus, Deniz] Northeastern Univ, Cognit Syst Lab, Boston, MA USA. [Bolon-Canedo, Veronica] Univ A Coruna, Dept Comp Sci, La Coruna, Spain. [Kalpathy-Cramer, Jayashree] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Patel, Samir N.] Weill Cornell Med Coll, Dept Ophthalmol, New York, NY USA. [Reynolds, James D.] SUNY Buffalo, Ross Eye Inst, Dept Ophthalmol, Buffalo, NY USA. [Horowitz, Jason] Columbia Univ, Dept Ophthalmol, New York, NY USA. [Hutcheson, Kelly] Sidra Med & Res Ctr, Dept Ophthalmol, Doha, Qatar. [Shapiro, Michael] Retina Consultants, Chicago, IL USA. [Repka, Michael X.] Johns Hopkins Univ, Sch Med, Wilmer Inst, Baltimore, MD USA. [Ferrone, Phillip] Long Isl Vitreoretinal Consultants, Great Neck, NY USA. [Drenser, Kimberly] Oakland Univ, Associated Retinal Consultants, Royal Oak, MI USA. [Ana Martinez-Castellanos, Maria] Asociac Evitar Ceguera Mexico, Mexico City, DF, Mexico. [Jonas, Karyn; Chan, R. V. Paul] Univ Illinois, Illinois Eye & Ear Infirm, Dept Ophthalmol & Visual Sci, Chicago, IL 60680 USA. [Chiang, Michael F.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. RP Chiang, MF (reprint author), Oregon Hlth & Sci Univ, Casey Eye Inst, Dept Ophthalmol, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA. EM chiangm@ohsu.edu RI Bolon-Canedo, Veronica/A-5573-2015; OI Bolon-Canedo, Veronica/0000-0002-0524-6427; Martinez-Castellanos, Maria/0000-0002-1265-3725; Jonas, Karyn /0000-0001-9038-6979 FU National Institutes of Health [RO1 EY19474, P30 EY010572, R21 EY022387]; Research to Prevent Blindness; St Giles Foundation; iNsight Foundation FX This study was supported by grants RO1 EY19474, P30 EY010572 (Drs Chiang and Campbell), and R21 EY022387 (Drs Erdogmus, Chiang, and Kalpathy-Cramer) from the National Institutes of Health, unrestricted departmental funding from Research to Prevent Blindness (Drs Campbell, Reynolds, Repka, Chan, and Chiang and Mss Patel, Ostmo, and Jonas), the St Giles Foundation (Dr Chan), and the iNsight Foundation (Dr Chan and Ms Jonas). NR 31 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD JUN PY 2016 VL 134 IS 6 BP 651 EP 657 DI 10.1001/jamaophthalmol.2016.0611 PG 7 WC Ophthalmology SC Ophthalmology GA DR0KL UT WOS:000379596300007 PM 27077667 ER PT J AU van Zyl, T Stagner, AM Lee, NG AF van Zyl, Tave Stagner, Anna M. Lee, Nahyoung Grace TI An Atypical Ulcerated Lesion at the Eyelid Margin SO JAMA OPHTHALMOLOGY LA English DT Editorial Material ID HERPES-ZOSTER OPHTHALMICUS C1 [van Zyl, Tave; Stagner, Anna M.; Lee, Nahyoung Grace] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA USA. RP Lee, NG (reprint author), Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol Ophthalm Plast Surg, 243 Charles St, Boston, MA 02114 USA. EM grace_lee@meei.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD JUN PY 2016 VL 134 IS 6 BP 703 EP 704 DI 10.1001/jamaophthalmol.2015.4965 PG 2 WC Ophthalmology SC Ophthalmology GA DR0KL UT WOS:000379596300017 PM 27054657 ER PT J AU Knudson, IM Melcher, JR AF Knudson, Inge M. Melcher, Jennifer R. TI Elevated Acoustic Startle Responses in Humans: Relationship to Reduced Loudness Discomfort Level, but not Self-Report of Hyperacusis SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE acoustic reflex; sound-level tolerance; hyperacusis ID PREPULSE INHIBITION; TINNITUS; SOUND; REFLEX; SCHIZOPHRENIA; HYPERSENSITIVITY; QUESTIONNAIRE; SENSITIZATION; HABITUATION; SENSITIVITY AB Increases in the acoustic startle response (ASR) of animals have been reported following experimental manipulations to induce tinnitus, an auditory disorder defined by phantom perception of sound. The increases in ASR have been proposed to signify the development of hyperacusis, a clinical condition defined by intolerance of normally tolerable sound levels. To test this proposal, the present study compared ASR amplitude to measures of sound-level tolerance (SLT) in humans, the only species in which SLT can be directly assessed. Participants had clinically normal/near-normal hearing thresholds, were free of psychotropic medications, and comprised people with tinnitus and without. ASR was measured as eyeblink-related electromyographic activity in response to a noise pulse presented at a range of levels and in two background conditions (noise and quiet). SLT was measured as loudness discomfort level (LDL), the lowest level of sound deemed uncomfortable, and via a questionnaire on the loudness of sounds in everyday life. Regardless of tinnitus status, ASR amplitude at a given stimulus level increased with decreasing LDL, but showed no relationship to SLT self-reported via the questionnaire. These relationships (or lack thereof) could not be attributed to hearing threshold, age, anxiety, or depression. The results imply that increases in ASR in the animal work signify decreases in LDL specifically and may not correspond to the development of hyperacusis as would be self-reported by a clinic patient. C1 [Knudson, Inge M.; Melcher, Jennifer R.] Harvard Med Sch, Dept Otolaryngol, Boston, MA USA. [Knudson, Inge M.; Melcher, Jennifer R.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. [Melcher, Jennifer R.] Harvard Div Med Sci, Speech & Hearing Biosci & Technol Program, Boston, MA USA. [Knudson, Inge M.; Melcher, Jennifer R.] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. RP Knudson, IM (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. EM inge_knudson@meei.harvard.edu OI Knudson, Inge/0000-0003-2774-8011 FU NIH [R21 DC012407, P30DC005209]; Tinnitus Research Consortium FX The authors thank John J. Guinan and M. Charles Liberman for helpful comments on a previous version of the manuscript. They are grateful for the help of Barbara Norris in preparation of the figures and tables. They thank the study volunteers for their time and effort. The work was supported by NIH R21 DC012407, the Tinnitus Research Consortium, and NIH P30DC005209. NR 34 TC 0 Z9 0 U1 4 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 EI 1438-7573 J9 JARO-J ASSOC RES OTO JI JARO PD JUN PY 2016 VL 17 IS 3 BP 223 EP 235 DI 10.1007/s10162-016-0555-y PG 13 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA DQ9JZ UT WOS:000379527500005 PM 26931342 ER PT J AU Wang, J Lewis, RF AF Wang, Joanne Lewis, Richard F. TI Abnormal Tilt Perception During Centrifugation in Patients with Vestibular Migraine SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE vestibular; migraine; perception; centrifugation; eye movements ID VESTIBULOOCULAR REFLEX; MOTION PERCEPTION; ROTATION; VERTIGO; CUES AB Vestibular migraine (VM), defined as vestibular symptoms caused by migraine mechanisms, is very common but poorly understood. Because dizziness is often provoked in VM patients when the semicircular canals and otolith organs are stimulated concurrently (e.g., tilting the head relative to gravity), we measured tilt perception and eye movements in patients with VM and in migraine and normal control subjects during fixed-radius centrifugation, a paradigm that simultaneously modulates afferent signals from the semicircular canals and otoliths organs. Twenty-four patients (8 in each category) were tested with a motion paradigm that generated an inter-aural centrifugal force of 0.36G, resulting in a 20 degrees tilt of the gravitoinertial force in the roll plane. We found that percepts of roll tilt developed slower in VM patients than in the two control groups, but that eye movement responses, including the shift in the eye's rotational axis, were equivalent in all three groups. These results demonstrate a change in vestibular perception in VM that is unaccompanied by changes in vestibular-mediated eye movements and suggest that either the brain's integration of canal and otolith signals or the dynamics of otolith responses are aberrant in patients with VM. C1 [Wang, Joanne] Case Western Univ, Sch Med, Cleveland, OH USA. [Lewis, Richard F.] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. [Lewis, Richard F.] Harvard Med Sch, Dept Otol & Laryngol, Boston, MA USA. [Lewis, Richard F.] Harvard Med Sch, Dept Neurol, Boston, MA USA. [Lewis, Richard F.] 243 Charles St, Boston, MA 02114 USA. RP Lewis, RF (reprint author), 243 Charles St, Boston, MA 02114 USA. EM Richard_lewis@meei.harvard.edu FU National Institutes of Health [DC012528] FX We thank Dan Merfeld for the comments on the study and Dave Balkwill for technical assistance. This study is supported by the National Institutes of Health grant DC012528 to RFL. NR 25 TC 2 Z9 2 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 EI 1438-7573 J9 JARO-J ASSOC RES OTO JI JARO PD JUN PY 2016 VL 17 IS 3 BP 253 EP 258 DI 10.1007/s10162-016-0559-7 PG 6 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA DQ9JZ UT WOS:000379527500007 PM 26956976 ER PT J AU Ionescu, DF Swee, MB Pavone, KJ Taylor, N Akeju, O Baer, L Nyer, M Cassano, P Mischoulon, D Alpert, JE Brown, EN Nock, MK Fava, M Cusin, C AF Ionescu, Dawn F. Swee, Michaela B. Pavone, Kara J. Taylor, Norman Akeju, Oluwaseun Baer, Lee Nyer, Maren Cassano, Paolo Mischoulon, David Alpert, Jonathan E. Brown, Emery N. Nock, Matthew K. Fava, Maurizio Cusin, Cristina TI Rapid and Sustained Reductions in Current Suicidal Ideation Following Repeated Doses of Intravenous Ketamine: Secondary Analysis of an Open-Label Study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article DE Suicide ID TREATMENT-RESISTANT DEPRESSION; RANDOMIZED CONTROLLED-TRIAL; D-ASPARTATE ANTAGONIST; MAJOR DEPRESSION; IMPLICIT COGNITION; LITHIUM TREATMENT; RATING-SCALE; DISORDER; PREVENTION; INFUSION AB Background: Ketamine rapidly reduces thoughts of suicide in patients with treatment-resistant depression who are at low risk for suicide. However, the extent to which ketamine reduces thoughts of suicide in depressed patients with current suicidal ideation remains unknown. Methods: Between April 2012 and October 2013, 14 outpatients with DSM-IV-diagnosed major depressive disorder were recruited for the presence of current, stable (>= 3 months) suicidal thoughts. They received open-label ketamine infusions over 3 weeks (0.5 mg/kg over 45 minutes for the first 3 infusions; 0.75 mg/kg over 45 minutes for the last 3). In this secondary analysis, the primary outcome measures of suicidal ideation (Columbia-Suicide Severity Rating Scale [C-SSRS] and the Suicide Item of the 28-item Hamilton Depression Rating Scale [HDRS28-SI]) were assessed at 240 minutes postinfusion and for 3 months thereafter in a naturalistic follow-up. Results: Over the course of the infusions (acute treatment phase), 7 of 14 patients (50%) showed remission of suicidal ideation on the C-SSRS Ideation scale (even among patients whose depression did not remit). There was a significant linear decrease in this score over time (P < .001), which approached significance even after controlling for severity of 6-item Hamilton Depression Rating Scale (HDRS6) core depression items (P = .05). Similarly, there were significant decreases in the C-SSRS Intensity (P < .01) and HDRS28-SI (P < .001) scores during the acute treatment phase. Two of the 7 patients who achieved remission during the acute treatment phase (29%) maintained their remission throughout a 3-month naturalistic follow-up. Conclusions: In this preliminary study, repeated doses of open-label ketamine rapidly and robustly decreased suicidal ideation in pharmacologically treated outpatients with treatment-resistant depression with stable suicidal thoughts; this decrease was maintained for at least 3 months following the final ketamine infusion in 2 patients. (C) Copyright 2016 Physicians Postgraduate Press, Inc. C1 [Ionescu, Dawn F.; Swee, Michaela B.; Pavone, Kara J.; Baer, Lee; Nyer, Maren; Cassano, Paolo; Mischoulon, David; Alpert, Jonathan E.; Fava, Maurizio; Cusin, Cristina] Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. [Pavone, Kara J.; Taylor, Norman; Akeju, Oluwaseun; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Akeju, Oluwaseun] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Ionescu, Dawn F.; Taylor, Norman; Baer, Lee; Nyer, Maren; Cassano, Paolo; Mischoulon, David; Alpert, Jonathan E.; Brown, Emery N.; Nock, Matthew K.; Fava, Maurizio; Cusin, Cristina] Harvard Med Sch, Boston, MA USA. RP Ionescu, DF (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM dionescu@partners.org RI Ionescu, Dawn/K-5675-2015 FU Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts; Harvard Clinical and Translational Science Center, from the National Center for Advancing Translational Science [8UL1TR000170-05] FX Funds from the Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts. Grant no. 8UL1TR000170-05, Harvard Clinical and Translational Science Center, from the National Center for Advancing Translational Science. NR 37 TC 3 Z9 3 U1 6 U2 9 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 JUN PY 2016 VL 77 IS 6 BP E719 EP E725 DI 10.4088/JCP.15m10056 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DQ6GM UT WOS:000379302500005 PM 27232360 ER PT J AU Perlis, ML Grandner, MA Brown, GK Basner, M Chakravorty, S Morales, KH Gehrman, PR Chaudhary, NS Thase, ME Dinges, DF AF Perlis, Michael L. Grandner, Michael A. Brown, Gregory K. Basner, Mathias Chakravorty, Subhajit Morales, Knashawn H. Gehrman, Philip R. Chaudhary, Ninad S. Thase, Michael E. Dinges, David F. TI Nocturnal Wakefulness as a Previously Unrecognized Risk Factor for Suicide SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article DE Sleep Disorders; Suicide ID SLEEP PROBLEMS; TIME; MILITARY; INSOMNIA; BEHAVIOR; ADULTS; PHASE AB Objective: Suicide is a major public health problem and the 10th leading cause of death in the United States. The identification of modifiable risk factors is essential for reducing the prevalence of suicide. Recently, it has been shown that insomnia and nightmares significantly increase the risk for suicidal ideation, attempted suicide, and death by suicide. While both forms of sleep disturbance may independently confer risk, and potentially be modifiable risk factors, it is also possible that simply being awake at night represents a specific vulnerability for suicide. The present analysis evaluates the frequency of completed suicide per hour while taking into account the percentage of individuals awake at each hour. Methods: Archival analyses were conducted estimating the time of fatal injury using the National Violent Death Reporting System for 2003-2010 and the proportion of the American population awake per hour across the 24-hour day using the American Time Use Survey. Results: The mean +/- SD incident rate from 06:00-23:59 was 2.2% +/- 0.7%, while the mean +/- SD incident rate from 00:00-05:59 was 10.3% +/- 4.9%. The maximum incident rate was from 02:00-02:59 (16.3%). Hour-by-hour observed values differed from those that would be expected by chance (P < .001), and when 6-hour blocks were examined, the observed frequency at night was 3.6 times higher than would be expected by chance (P < .001). Conclusions: Being awake at night confers greater risk for suicide than being awake at other times of the day, suggesting that disturbances of sleep or circadian neurobiology may potentiate suicide risk. (C) Copyright 2016 Physicians Postgraduate Press, Inc. C1 [Perlis, Michael L.; Grandner, Michael A.; Chakravorty, Subhajit; Gehrman, Philip R.; Chaudhary, Ninad S.] Univ Penn, Dept Psychiat, Perelman Sch Med, Behav Sleep Med Program, Philadelphia, PA 19104 USA. [Perlis, Michael L.; Grandner, Michael A.; Basner, Mathias; Chakravorty, Subhajit; Gehrman, Philip R.; Dinges, David F.] Univ Penn, Perelman Sch Med, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA. [Perlis, Michael L.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Brown, Gregory K.] Univ Penn, Dept Psychiat, Perelman Sch Med, Ctr Prevent Suicide, Philadelphia, PA 19104 USA. [Basner, Mathias; Dinges, David F.] Univ Penn, Dept Psychiat, Perelman Sch Med, Div Sleep & Chronobiol,Unit Expt Psychiat, Philadelphia, PA 19104 USA. [Chakravorty, Subhajit] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. [Morales, Knashawn H.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Chaudhary, Ninad S.] Washington Univ, Populat Hlth Sci Program, St Louis, MO USA. [Thase, Michael E.] Univ Penn, Dept Psychiat, Perelman Sch Med, Mood & Anxiety Disorders Treatment & Res Program, Philadelphia, PA 19104 USA. [Grandner, Michael A.] Univ Arizona, Dept Psychiat, Tucson, AZ USA. [Chaudhary, Ninad S.] Univ Alabama Birmingham, Sch Med, Dept Emergency Med, Birmingham, AL USA. [Chaudhary, Ninad S.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. RP Perlis, ML (reprint author), Univ Penn, Dept Psychiat, Behav Sleep Med Program, 3535 Market St,Ste 670, Philadelphia, PA 19104 USA. EM mperlis@upenn.edu FU National Institute on Aging [R01AG041783]; National Center for Complementary and Alternative Medicine [R01AT003332]; National Institute of Mental Health [R01MH077900, R01MH086572, R21MH103963, R01MH082794]; National Institute of Environmental Health Services [R21ES022931]; National Heart, Lung, and Blood Institute [K23HL110216]; National Institute of Nursing Research [R01NR004281]; National Space Biomedical Research Institute through the National Aeronautics and Space Administration [NCC 9-58]; US Department of Veterans Affairs [IK2CX000855] FX The study had no direct support by grant funding. Partial salary support was provided by the National Institute on Aging grant R01AG041783 (Drs Perlis and Morales); National Center for Complementary and Alternative Medicine grant R01AT003332 (Drs Perlis and Morales); National Institute of Mental Health grant R01MH077900 (Drs Perlis and Morales), R01MH086572 (Dr Brown), R21MH103963 (Dr Gehrman), and R01MH082794 (Dr Thase); National Institute of Environmental Health Services grant R21ES022931 (Dr Grandner); National Heart, Lung, and Blood Institute grant K23HL110216 (Dr Grandner); National Institute of Nursing Research grant R01NR004281 (Dr Dinges); National Space Biomedical Research Institute grant NCC 9-58 through the National Aeronautics and Space Administration (Dr Basner); and US Department of Veterans Affairs grant IK2CX000855 (Dr Chakravorty). NR 27 TC 0 Z9 0 U1 2 U2 2 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 JUN PY 2016 VL 77 IS 6 BP E726 EP E733 DI 10.4088/JCP.15m10131 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DQ6GM UT WOS:000379302500006 PM 27337421 ER PT J AU Frodermann, V van Duijn, J van Puijvelde, GHM van Santbrink, PJ Lagraauw, HM de Vries, MR Quax, PHA Bot, I Foks, AC de Jager, SCA Kuiper, J AF Frodermann, V. van Duijn, J. van Puijvelde, G. H. M. van Santbrink, P. J. Lagraauw, H. M. de Vries, M. R. Quax, P. H. A. Bot, I. Foks, A. C. de Jager, S. C. A. Kuiper, J. TI Heat-killed Staphylococcus aureus reduces atherosclerosis by inducing anti-inflammatory macrophages SO JOURNAL OF INTERNAL MEDICINE LA English DT Article DE atherosclerosis; immunology; inflammation; macrophages; Staphylococcus aureus ID TOLL-LIKE RECEPTOR-2; REGULATORY T-CELLS; NITRIC-OXIDE; PHOSPHATIDYLINOSITOL-3 KINASE; PORPHYROMONAS-GINGIVALIS; APOPTOTIC CELLS; GENE-TRANSFER; IFN-GAMMA; ACTIVATION; INTERLEUKIN-10 AB Background. Staphylococcus aureus cell wall components can induce IL-10 responses by immune cells, which may be atheroprotective. Therefore, in this study, we investigated whether heat-killed S. aureus (HK-SA) could inhibit the development of atherosclerosis. Methods. Atherosclerosis-susceptible LDL receptor-deficient mice were administered intraperitoneal HK-SA twice weekly and fed a Western-type diet for 6 weeks. Results. HK-SA administration resulted in a 1.6-fold increase in IL-10 production by peritoneal macrophages and splenocytes, and a 12-fold increase in serum IL-10 levels. Moreover, aortic plaque ICAM-1, VCAM-1 and CCL2 expression levels were significantly downregulated by on average 40%. HK-SA-treated mice had reduced numbers of inflammatory Ly-6C(hi) monocytes as well as Th1 and Th17 cells in the circulation and spleen, respectively. Attenuated leucocyte recruitment resulted in a significant inhibition of macrophage and T cell infiltration in atherosclerotic plaques, culminating in a significant 34% reduction in the development of atherosclerosis. To determine the effects of intraperitoneal HK-SA treatment, we stimulated macrophages with HK-SA in vitro. This resulted in a significant toll-like receptor 2 (TLR2)-dependent increase in IL-10, arginase-1, iNOS, TNF-alpha, PD-L1, CCL22 and indoleamine 2,3-dioxygenase expression. It was found that phosphoinositide 3-kinase crucially determined the balance of pro-and anti-inflammatory gene expression. The HK-SA-induced macrophage phenotype resembled M2b-like immunoregulatory macrophages. Conclusions. We have shown that HK-SA treatment induces strong anti-inflammatory IL-10 responses by macrophages, which are largely dependent on TLR2 and PI3K, and protects against the development of atherosclerosis. Commensalism with S. aureus could thus reduce cardiovascular events. C1 [Frodermann, V.; van Duijn, J.; van Puijvelde, G. H. M.; van Santbrink, P. J.; Lagraauw, H. M.; Bot, I.; Foks, A. C.; de Jager, S. C. A.; Kuiper, J.] Leiden Univ, Leiden Acad Ctr Drug Res, Div Biopharmaceut, Einsteinweg 55, NL-2333 CC Leiden, Netherlands. [de Vries, M. R.; Quax, P. H. A.] Leiden Univ, Med Ctr, Dept Surg, NL-2333 CC Leiden, Netherlands. [de Vries, M. R.; Quax, P. H. A.] Leiden Univ, Med Ctr, Einthoven Lab Expt Vasc Med, NL-2333 CC Leiden, Netherlands. [de Jager, S. C. A.] Univ Med Ctr Utrecht, Lab Expt Cardiol, Utrecht, Netherlands. [de Jager, S. C. A.] Univ Med Ctr Utrecht, Lab Translat Immunol, Utrecht, Netherlands. [Frodermann, V.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Frodermann, V.] Harvard Med Sch, Boston, MA USA. RP Kuiper, J (reprint author), Leiden Univ, Leiden Acad Ctr Drug Res, Div Biopharmaceut, Einsteinweg 55, NL-2333 CC Leiden, Netherlands.; Frodermann, V (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.; Frodermann, V (reprint author), Harvard Med Sch, Boston, MA USA. EM vfrodermann@mgh.harvard.edu; j.kuiper@lacdr.leidenuniv.nl OI Quax, Paul/0000-0002-6853-5760 FU Netherlands CardioVascular Research Initiative; Dutch Heart Foundation [2009B093, 2007T039, 2010B244]; Dutch Federation of University Medical Centres; Netherlands Organisation for Health Research and Development; KNAW\Royal Netherlands Academy of Arts and Sciences [CVON2011-19] FX This work was supported by the Netherlands CardioVascular Research Initiative, the Dutch Heart Foundation (grant numbers 2009B093 to VF, 2007T039 to GHMvP and 2010B244 to HML), the Dutch Federation of University Medical Centres, the Netherlands Organisation for Health Research and Development and the KNAW vertical bar Royal Netherlands Academy of Arts and Sciences for the GENIUS project 'Generating the best evidence-based pharmaceutical targets for atherosclerosis' (grant number CVON2011-19). NR 50 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0954-6820 EI 1365-2796 J9 J INTERN MED JI J. Intern. Med. PD JUN PY 2016 VL 279 IS 6 BP 592 EP 605 DI 10.1111/joim.12484 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA DQ9GG UT WOS:000379517800009 PM 26914137 ER PT J AU Nagahashi, M Yamada, A Miyazaki, H Allegood, JC Tsuchida, J Aoyagi, T Huang, WC Terracina, KP Adams, BJ Rashid, OM Milstien, S Wakai, T Spiegel, S Takabe, K AF Nagahashi, Masayuki Yamada, Akimitsu Miyazaki, Hiroshi Allegood, Jeremy C. Tsuchida, Junko Aoyagi, Tomoyoshi Huang, Wei-Ching Terracina, Krista P. Adams, Barbara J. Rashid, Omar M. Milstien, Sheldon Wakai, Toshifumi Spiegel, Sarah Takabe, Kazuaki TI Interstitial Fluid Sphingosine-1-Phosphate in Murine Mammary Gland and Cancer and Human Breast Tissue and Cancer Determined by Novel Methods SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE Cancer; Endothelial cells; Interstitial fluid; Mass spectrometry; Sphingolipids; Sphingosine-1-phosphate ID SPHINGOSINE KINASE 1; PROTEASOMAL-DEGRADATION; POOR SURVIVAL; FTY720; 1-PHOSPHATE; PROGRESSION; CELLS; INFLAMMATION; METASTASIS; COLITIS AB The tumor microenvironment is a determining factor for cancer biology and progression. Sphingosine-1-phosphate (S1P), produced by sphingosine kinases (SphKs), is a bioactive lipid mediator that regulates processes important for cancer progression. Despite its critical roles, the levels of S1P in interstitial fluid (IF), an important component of the tumor microenvironment, have never previously been measured due to a lack of efficient methods for collecting and quantifying IF. The purpose of this study is to clarify the levels of S1P in the IF from murine mammary glands and its tumors utilizing our novel methods. We developed an improved centrifugation method to collect IF. Sphingolipids in IF, blood, and tissue samples were measured by mass spectrometry. In mice with a deletion of SphK1, but not SphK2, levels of S1P in IF from the mammary glands were greatly attenuated. Levels of S1P in IF from mammary tumors were reduced when tumor growth was suppressed by oral administration of FTY720/fingolimod. Importantly, sphingosine, dihydro-sphingosine, and S1P levels, but not dihydro-S1P, were significantly higher in human breast tumor tissue IF than in the normal breast tissue IF. To our knowledge, this is the first reported S1P IF measurement in murine normal mammary glands and mammary tumors, as well as in human patients with breast cancer. S1P tumor IF measurement illuminates new aspects of the role of S1P in the tumor microenvironment. C1 [Nagahashi, Masayuki; Yamada, Akimitsu; Aoyagi, Tomoyoshi; Huang, Wei-Ching; Terracina, Krista P.; Adams, Barbara J.; Takabe, Kazuaki] Virginia Commonwealth Univ, Sch Med, Dept Surg, Div Surg Oncol, POB 980011,West Hosp 7-402,1200 East Broad St, Richmond, VA 23298 USA. [Nagahashi, Masayuki; Yamada, Akimitsu; Aoyagi, Tomoyoshi; Huang, Wei-Ching; Terracina, Krista P.; Adams, Barbara J.; Takabe, Kazuaki] Massey Canc Ctr, POB 980011,West Hosp 7-402,1200 East Broad St, Richmond, VA 23298 USA. [Nagahashi, Masayuki; Yamada, Akimitsu; Allegood, Jeremy C.; Aoyagi, Tomoyoshi; Huang, Wei-Ching; Terracina, Krista P.; Adams, Barbara J.; Milstien, Sheldon; Spiegel, Sarah; Takabe, Kazuaki] Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, POB 980011,West Hosp 7-402,1200 East Marshall St, Richmond, VA 23298 USA. [Nagahashi, Masayuki; Yamada, Akimitsu; Allegood, Jeremy C.; Aoyagi, Tomoyoshi; Huang, Wei-Ching; Terracina, Krista P.; Adams, Barbara J.; Milstien, Sheldon; Spiegel, Sarah; Takabe, Kazuaki] Massey Canc Ctr, POB 980011,West Hosp 7-402,1200 East Marshall St, Richmond, VA 23298 USA. [Nagahashi, Masayuki; Tsuchida, Junko; Wakai, Toshifumi] Niigata Univ, Grad Sch Med & Dent Sci, Div Digest & Gen Surg, Chuo Ku, 1-757 Asahimachi Dori, Niigata, Niigata 9518510, Japan. [Miyazaki, Hiroshi] Kojin Hosp, Gen Internal Med Sect, 1-710 Shikenya, Nagoya, Aichi 4638530, Japan. [Rashid, Omar M.] Holy Cross Hosp, Michael & Dianne Bienes Comprehens Canc Ctr, 4725 North Fed Highway, Ft Lauderdale, FL 33308 USA. [Rashid, Omar M.] Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. [Rashid, Omar M.] Univ Miami, Miller Sch Med, 1600 NW10th Ave, Miami, FL 33136 USA. [Takabe, Kazuaki] Roswell Pk Canc Inst, Breast Surg, Elm & Carlton St, Buffalo, NY 14263 USA. RP Nagahashi, M; Takabe, K (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Surg, Div Surg Oncol, POB 980011,West Hosp 7-402,1200 East Broad St, Richmond, VA 23298 USA.; Nagahashi, M; Takabe, K (reprint author), Massey Canc Ctr, POB 980011,West Hosp 7-402,1200 East Broad St, Richmond, VA 23298 USA.; Nagahashi, M; Takabe, K (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, POB 980011,West Hosp 7-402,1200 East Marshall St, Richmond, VA 23298 USA.; Nagahashi, M; Takabe, K (reprint author), Massey Canc Ctr, POB 980011,West Hosp 7-402,1200 East Marshall St, Richmond, VA 23298 USA.; Nagahashi, M (reprint author), Niigata Univ, Grad Sch Med & Dent Sci, Div Digest & Gen Surg, Chuo Ku, 1-757 Asahimachi Dori, Niigata, Niigata 9518510, Japan.; Takabe, K (reprint author), Roswell Pk Canc Inst, Breast Surg, Elm & Carlton St, Buffalo, NY 14263 USA. EM mnagahashi@med.niigata-u.ac.jp; kazutakabe@gmail.com FU Japan Society for the Promotion of Science (JSPS) [15H05676, 15 K15471]; Uehara Memorial Foundation; Nakayama Cancer Research Institute; Takeda Science Foundation; Tsukada Medical Foundation; JSPS [16 K19888]; NIH/NCI [R01CA160688, R01CA61774]; Susan G. Komen Investigator Initiated Research Grant [IIR12222224]; DoD BCRP program [W81XWH-14-1-0086]; [T32CA085159] FX MN was a Japan Society for the Promotion of Science Postdoctoral Fellow. MN is supported by the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research Grant Number 15H05676 and 15 K15471, the Uehara Memorial Foundation, Nakayama Cancer Research Institute, Takeda Science Foundation, and Tsukada Medical Foundation. JT is supported by the JSPS Grant-in-Aid for Scientific Research Grant Number 16 K19888. KT is supported by NIH/NCI grant R01CA160688 and Susan G. Komen Investigator Initiated Research Grant IIR12222224. SS is supported by NIH/NCI grant R01CA61774 and in part by the DoD BCRP program under award number W81XWH-14-1-0086. KPT is supported by T32CA085159. NR 40 TC 0 Z9 0 U1 2 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 EI 1573-7039 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD JUN PY 2016 VL 21 IS 1-2 BP 9 EP 17 DI 10.1007/s10911-016-9354-7 PG 9 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA DQ6PJ UT WOS:000379327000002 PM 27194029 ER PT J AU Kauth, MR Shipherd, JC AF Kauth, Michael R. Shipherd, Jillian C. TI Transforming a System: Improving Patient-Centered Care for Sexual and Gender Minority Veterans SO LGBT HEALTH LA English DT Editorial Material DE LGBT; organizational change; patient-centered care; training; veterans ID TRANSGENDER VETERANS; MENTAL-HEALTH C1 [Kauth, Michael R.; Shipherd, Jillian C.] Vet Hlth Adm, LGBT Program, Off Patient Care Serv, Washington, DC USA. [Kauth, Michael R.] VA South Cent Mental Illness Res Educ & Clin Ctr, Houston, TX USA. [Kauth, Michael R.] VA South Cent MIRECC, Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd,ATTN VA152, Houston, TX 77030 USA. [Kauth, Michael R.] Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Shipherd, Jillian C.] Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Shipherd, Jillian C.] VA Boston Healthcare Syst, Mental Hlth, Boston, MA USA. [Shipherd, Jillian C.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP Kauth, MR (reprint author), VA South Cent MIRECC, Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd,ATTN VA152, Houston, TX 77030 USA. EM michael.kauth@va.gov NR 18 TC 2 Z9 2 U1 3 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2325-8292 EI 2325-8306 J9 LGBT HEALTH JI LGBT Health PD JUN PY 2016 VL 3 IS 3 BP 177 EP 179 DI 10.1089/lgbt.2016.0047 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DR1KM UT WOS:000379664400001 PM 27135527 ER PT J AU Caska-Wallace, CM Katon, JG Lehavot, K McGinn, MM Simpson, TL AF Caska-Wallace, Catherine M. Katon, Jodie G. Lehavot, Keren McGinn, Meghan M. Simpson, Tracy L. TI Posttraumatic Stress Disorder Symptom Severity and Relationship Functioning Among Partnered Heterosexual and Lesbian Women Veterans SO LGBT HEALTH LA English DT Article DE military; partner support; PTSD; relationship satisfaction; sexual orientation; women Veterans ID SOCIAL SUPPORT; MENTAL-HEALTH; RELATIONSHIP QUALITY; FAMILY ADJUSTMENT; VIETNAM VETERANS; PTSD; GAY; COUPLES; IRAQ; AFGHANISTAN AB Purpose: Few studies have examined associations of posttraumatic stress disorder (PTSD) and relationship satisfaction among women Veterans, and no research has explored these factors in lesbian women Veterans, a large subgroup that may have unique concerns. This study examined the link between PTSD and relationship satisfaction in partnered heterosexual and lesbian women Veterans and evaluated potential moderation by sexual orientation, partner support, and conflict. Methods: Women Veterans (heterosexual n=260; lesbian n=128) were recruited nationally to complete a cross-sectional online survey. Multiple linear regression models were used to evaluate moderation, using two- and three-way interactions. Results: Partner support moderated the association between PTSD symptoms and relationship satisfaction to a different degree for heterosexual and lesbian women Veterans, playing a more prominent role in this association for lesbian women. Specifically, for lesbians with low partner support, as PTSD symptoms worsened, relationship satisfaction decreased at a steeper rate than for heterosexual women with low partner support. On the other hand, for lesbians with high partner support, as PTSD symptoms worsened, relationship satisfaction decreased less sharply than for heterosexual women with high partner support. Degree of conflict was highly correlated with relationship satisfaction and also appeared to moderate these relations differently by sexual orientation. Conclusion: These findings suggest that women Veterans with PTSD experience impairments in their romantic relationships, which vary by sexual orientation, partner support, and conflict. Partner support and conflict may be important targets in assessment and therapy for women Veterans with PTSD, and especially so for sexual minorities. C1 [Caska-Wallace, Catherine M.; McGinn, Meghan M.] VA Puget Sound Hlth Care Syst, Mental Hlth Serv, 1660 S Columbian Way 116MHC, Seattle, WA 98108 USA. [Caska-Wallace, Catherine M.; Lehavot, Keren; McGinn, Meghan M.; Simpson, Tracy L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Katon, Jodie G.; Lehavot, Keren] VA Puget Sound Hlth Care Syst, HSR&D, Seattle, WA USA. [Katon, Jodie G.; Lehavot, Keren] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Katon, Jodie G.] Womens Hlth Serv, US Dept Vet Affairs VA, Off Patient Care Serv, Washington, DC USA. [Lehavot, Keren; Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, MIRECC, Seattle, WA USA. [Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, CESATE, Seattle, WA USA. RP Caska-Wallace, CM (reprint author), VA Puget Sound Hlth Care Syst, Mental Hlth Serv, 1660 S Columbian Way 116MHC, Seattle, WA 98108 USA. EM catherine.wallace@va.gov FU VISN-20 Mental Illness Research, Education, and Clinical Center (MIRECC); VA CSR&D Career Development Award [IK2 CX000867] FX This research was supported by a research grant to K. Lehavot and T. Simpson from the VISN-20 Mental Illness Research, Education, and Clinical Center (MIRECC). Dr. Lehavot's effort was supported by a VA CSR&D Career Development Award (IK2 CX000867). This material is the result of work supported by resources from the VA Puget Sound Health Care System, Seattle, Washington. The views expressed in this article are those of the authors and do not represent the views of the Department of Veterans Affairs or the United States government. NR 34 TC 0 Z9 0 U1 5 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2325-8292 EI 2325-8306 J9 LGBT HEALTH JI LGBT Health PD JUN PY 2016 VL 3 IS 3 BP 186 EP 192 DI 10.1089/lgbt.2015.0097 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DR1KM UT WOS:000379664400004 PM 26895547 ER PT J AU Biello, KB Oldenburg, CE Rosenberger, J Mayer, KH Novak, D Mimiaga, MJ AF Biello, Katie B. Oldenburg, Catherine E. Rosenberger, Joshua Mayer, Kenneth H. Novak, David Mimiaga, Matthew J. TI Is Involvement in Sex Work Associated with Engagement in HIV-Related Medical Care in Latin American Men Who Have Sex with Men? Results of a Large, Multinational Internet Survey SO LGBT HEALTH LA English DT Article DE HIV; Latin America; medical care; medication adherence; men who have sex with men (MSM); transactional sex ID CHI MINH CITY; ANTIRETROVIRAL THERAPY; TRANSACTIONAL SEX; STIGMA; SERVICES; INFECTION; HEALTH; RISK; EPIDEMIOLOGY; PREVENTION AB Men who have sex with men (MSM) who engage in transactional sex are at increased HIV risk, and face complex barriers to care seeking. Among 2,035 men recruited through an MSM social/sexual networking website in Latin America and who reported being HIV-infected, 186 (9.1%) reported being paid for sex with another man in the past year. Engagement in transactional sex was associated with decreased odds of receiving medical care for HIV (AOR=0.57, 95% CI=0.37-0.85). No significant differences were seen in being on antiretroviral therapy (ART) or ART adherence once in care. Interventions in this population should focus on reducing barriers to engagement in care. C1 [Biello, Katie B.; Oldenburg, Catherine E.; Mimiaga, Matthew J.] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Biello, Katie B.; Mayer, Kenneth H.; Mimiaga, Matthew J.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Rosenberger, Joshua] George Mason Univ, Dept Global & Community Hlth, Fairfax, VA 22030 USA. [Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Mayer, Kenneth H.] Harvard Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA USA. [Novak, David] Online Buddies Inc, OLB Res Inst, Cambridge, MA USA. [Mimiaga, Matthew J.] Harvard Med Sch, Dept Psychiat, Boston, MA USA. [Mimiaga, Matthew J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Biello, KB (reprint author), Fenway Inst, 1340 Boylston St, Boston, MA 02215 USA. EM kbiello@fenwayhealth.org FU National Institute of Allergy and Infectious Diseases [T32AI007535]; National Institute on Drug Abuse [T32DA0131911] FX CEO was supported by National Institute of Allergy and Infectious Diseases T32AI007535 (PI: Seage) and National Institute on Drug Abuse T32DA0131911 (PI: Flanigan). NR 25 TC 0 Z9 0 U1 4 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2325-8292 EI 2325-8306 J9 LGBT HEALTH JI LGBT Health PD JUN PY 2016 VL 3 IS 3 BP 233 EP 237 DI 10.1089/lgbt.2015.0006 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DR1KM UT WOS:000379664400011 PM 26789395 ER PT J AU Kaunitz, AM Bryant, A AF Kaunitz, Andrew M. Bryant, Allison TI Clinical trials of new treatments for menopausal conditions: paying attention to race SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID VASOMOTOR SYMPTOMS; THERAPY C1 [Kaunitz, Andrew M.] Univ Florida, Coll Med Jacksonville, Dept Obstet & Gynecol, Jacksonville, FL 32218 USA. [Bryant, Allison] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Kaunitz, AM (reprint author), Univ Florida, Coll Med Jacksonville, Dept Obstet & Gynecol, Jacksonville, FL 32218 USA. NR 12 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JUN PY 2016 VL 23 IS 6 BP 589 EP 590 DI 10.1097/GME.0000000000000637 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DQ7EU UT WOS:000379370500003 PM 27070806 ER EF