FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Xu, HY Yang, YJ Tang, XR Sabatine, M Wiviott, S AF Xu, Haiyan Yang, YueJin Tang, Xinran Sabatine, Marc Wiviott, Stephen TI ACUTE MYOCARDIAL INFARCTION CARE ACROSS THREE LEVELS OF HOSPITALS IN CHINA: A REPORT FROM THE CHINA ACUTE MYOCARDIAL INFARCTION REGISTRY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Fuwai Hosp, Beijing, Peoples R China. TIMI Study Grp, Boston, MA USA. NR 0 TC 0 Z9 1 U1 2 U2 2 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 MAR 17 PY 2015 VL 65 IS 10 SU S MA 1175-068 BP A137 EP A137 DI 10.1016/S0735-1097(15)60137-1 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328800138 ER PT J AU Young, M Kennedy, K Yeh, R AF Young, Michael Kennedy, Kevin Yeh, Robert TI NATIONAL UTILIZATION PATTERNS OF TRANSCATHETER AORTIC VALVE REPLACEMENT SHORTLY AFTER DEVICE APPROVAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT Scientific Session of the American-College-of-Cardiology (ACC) CY MAR 14-16, 2015 CL San Diego, CA SP Amer Coll Cardiol C1 Vanderbilt Univ, Med Ctr, Nashville, TN USA. Massachusetts Gen Hosp, Boston, MA 02114 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2015 VL 65 IS 10 SU S MA 1261-348 BP A2030 EP A2030 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL0ND UT WOS:000375328802352 ER PT J AU Elder, GA Sosa, MAG De Gasperi, R Stone, JR Dickstein, DL Haghighi, F Hof, PR Ahlers, ST AF Elder, Gregory A. Sosa, Miguel A. Gama De Gasperi, Rita Stone, James Radford Dickstein, Dara L. Haghighi, Fatemeh Hof, Patrick R. Ahlers, Stephen T. TI Vascular and inflammatory factors in the pathophysiology of blast-induced brain injury SO FRONTIERS IN NEUROLOGY LA English DT Review DE animal models; blast; inflammation; traumatic brain injury; vascular pathology ID CENTRAL-NERVOUS-SYSTEM; POSTTRAUMATIC-STRESS-DISORDER; CHRONIC TRAUMATIC ENCEPHALOPATHY; MISSILE EXTREMITY IMPACT; PRESSURE WAVE INJURIES; TIME-DEPENDENT CHANGES; NON-PENETRATIVE BLAST; SHOCK-WAVE; RAT MODEL; INDUCED NEUROTRAUMA AB Blast-related traumatic brain injury (TBI) has received much recent attention because of its frequency in the conflicts in Iraq and Afghanistan. This renewed interest has led to a rapid expansion of clinical and animal studies related to blast. In humans, high-level blast exposure is associated with a prominent hemorrhagic component. In animal models, blast exerts a variety of effects on the nervous system including vascular and inflammatory effects that can be seen with even low-level blast exposures which produce minimal or no neuronal pathology. Acutely, blast exposure in animals causes prominent vasospasm and decreased cerebral blood flow along with blood-brain barrier breakdown and increased vascular permeability. Besides direct effects on the central nervous system, evidence supports a role fora thoracically mediated effect of blast; whereby, pressure waves transmitted through the systemic circulation damage the brain. Chronically, a vascular pathology has been observed that is associated with alterations of the vascular extracellular matrix. Sustained microglial and astroglial reactions occur after blast exposure. Markers of a central and peripheral inflammatory response are found for sustained periods after blast injury and include elevation of inflammatory cytokines and other inflammatory mediators. At low levels of blast exposure, a microvascular pathology has been observed in the presence of an otherwise normal brain parenchyma, suggesting that the vasculature may be selectively vulnerable to blast injury. Chronic immune activation in brain following vascular injury may lead to neurobehavioral changes in the absence of direct neuronal pathology. Strategies aimed at preventing or reversing vascular damage or modulating the immune response may improve the chronic neuropsychiatric symptoms associated with blast-related TBI. C1 [Elder, Gregory A.] James J Peters Dept Vet Affairs Med Ctr, Neurol Serv, Bronx, NY 10468 USA. [Elder, Gregory A.; Sosa, Miguel A. Gama; De Gasperi, Rita; Haghighi, Fatemeh] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Elder, Gregory A.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Elder, Gregory A.; Sosa, Miguel A. Gama; De Gasperi, Rita; Dickstein, Dara L.; Haghighi, Fatemeh; Hof, Patrick R.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Sosa, Miguel A. Gama; De Gasperi, Rita; Haghighi, Fatemeh] James J Peters Dept Vet Affairs Med Ctr, Res & Dev Serv, Bronx, NY 10468 USA. [Stone, James Radford] Univ Virginia, Dept Radiol & Med Imaging, Charlottesville, VA USA. [Stone, James Radford] Univ Virginia, Dept Neurosurg, Charlottesville, VA USA. [Dickstein, Dara L.; Haghighi, Fatemeh; Hof, Patrick R.] Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA. [Dickstein, Dara L.; Hof, Patrick R.] Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Care, New York, NY 10029 USA. [Ahlers, Stephen T.] Naval Med Res Ctr, Dept Neurotrauma, Operat & Undersea Med Directorate, Silver Spring, MD USA. RP Elder, GA (reprint author), James J Peters Dept Vet Affairs Med Ctr, Neurol Serv, 3E16,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM gregory.elder@va.gov FU Department of Veterans Affairs; Veterans Health Administration; Rehabilitation Research and Development Service [1I01RX000179-01, 1I01RX000996-01] FX The authors have received research support from the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service Awards 1I01RX000179-01 and 1I01RX000996-01. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government. STA is a military service member (or employe of the U.S. Government). This work was prepared as part of his official duties. Title 17 U.S.C. 105 provides that copyright protection under this title is not available for any work of the United States Government. Title 17 U.S.C. 101 defines a U.S. Government work as a work prepared by a military service member or employe of the U.S. Government as part of that person's official duties. NR 147 TC 9 Z9 10 U1 3 U2 7 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-2295 J9 FRONT NEUROL JI Front. Neurol. PD MAR 16 PY 2015 VL 6 AR UNSP 48 DI 10.3389/fneur.2015.00048 PG 22 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CU8CX UT WOS:000363769900001 PM 25852632 ER PT J AU Ross, JM Coxe, S Schuster, RM Rojas, A Gonzalez, R AF Ross, J. Megan Coxe, Stefany Schuster, Randi M. Rojas, Angelica Gonzalez, Raul TI The moderating effects of cannabis use and decision making on the relationship between conduct disorder and risky sexual behavior SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article DE Conduct disorder; Risky sexual behavior; Cannabis; Decision making ID LIFE-COURSE-PERSISTENT; VENTROMEDIAL PREFRONTAL CORTEX; LIMITED ANTISOCIAL PATHWAYS; ADOLESCENT SUBSTANCE USE; YOUNG-ADULTS; UNITED-STATES; CHILDHOOD PREDICTORS; TAKING BEHAVIOR; GAMBLING TASK; MARIJUANA USE AB Risky sexual behavior (RSB) is a current public health concern affecting adolescents and young adults. Conduct disorder, cannabis use, and decision-making (DM) ability are interrelated constructs that are relevant to RSB; however, there is little research on the association of DM and RSB. Participants were 79 cannabis users assessed through self-report measures of RSB and mental health and a timeline follow-back procedure for substance use. DM ability was assessed via the Iowa Gambling Task. We found that more conduct disorder symptoms accounted for unique variance in measures of overall RSB and an earlier initiation of oral sex, even when taking into account DM and cannabis use. Amount of cannabis use and DM ability moderated the relationships between number of conduct disorder symptoms and number of oral sex partners and age of initiation for vaginal sex. An increase in conduct disorder symptoms was associated with more oral sex partners when DM was poor and fewer partners when DM was better; however, this relationship was only present at higher levels of cannabis use. Furthermore, when DM was poor, more conduct disorder symptoms predicted a younger age of initiation of vaginal sex, with the age decreasing as amount of cannabis use increased. Determining how DM influences RSB may assist in the identification of novel treatment approaches to reduce engagement in RSB. C1 [Ross, J. Megan; Coxe, Stefany; Rojas, Angelica; Gonzalez, Raul] Florida Int Univ, Dept Psychol, Ctr Children & Families, Miami, FL 33199 USA. [Schuster, Randi M.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, Boston, MA 02114 USA. RP Ross, JM (reprint author), Florida Int Univ, Ctr Children & Families, 11200 SW 8th St,AHC1 Rm 140, Miami, FL 33199 USA. EM jmross@fiu.edu FU National Institute on Drug Abuse [K23 DA023560, R01 DA031176, R01 DA033156] FX This work was supported by the National Institute on Drug Abuse [grant number K23 DA023560], [grant number R01 DA031176], [grant number R01 DA033156] (PI: R. Gonzalez). NR 76 TC 1 Z9 1 U1 4 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1380-3395 EI 1744-411X J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD MAR 16 PY 2015 VL 37 IS 3 BP 303 EP 315 DI 10.1080/13803395.2015.1010489 PG 13 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA CI7FV UT WOS:000354929200007 PM 25832553 ER PT J AU Gard, T Taquet, M Dixit, R Holzel, BK Dickerson, BC Lazar, SW AF Gard, Tim Taquet, Maxime Dixit, Rohan Hoelzel, Britta K. Dickerson, Bradford C. Lazar, Sara W. TI Greater widespread functional connectivity of the caudate in older adults who practice kripalu yoga and vipassana meditation than in controls SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE caudate; functional connectivity; graph theory; degree centrality; yoga; mindfulness meditation; aging; basal ganglia-thalamocortical circuits ID STRESS REDUCTION PROGRAM; BRAIN GABA LEVELS; BASAL GANGLIA; INDIVIDUAL-DIFFERENCES; NETWORK CONNECTIVITY; TERM MEDITATION; WORKING-MEMORY; RESTING STATE; MINDFULNESS; CIRCUITS AB There has been a growing interest in understanding how contemplative practices affect brain functional organization. However, most studies have restricted their exploration to predefined networks. Furthermore, scientific comparisons of different contemplative traditions are largely lacking. Here we explored differences in whole brain resting state functional connectivity between experienced yoga practitioners, experienced meditators, and matched controls. Analyses were repeated in an independent sample of experienced meditators and matched controls. Analyses utilizing Network Based Statistics (Zalesky et al., 2010) revealed difference components for yoga practitioners > controls and meditators > controls in which the right caudate was a central node. Follow up analyses revealed that yoga practitioners and meditators had significantly greater degree centrality in the caudate than controls. This greater degree centrality was not driven by single connections but by greater connectivity between the caudate and numerous brain regions. Findings of greater caudate connectivity in meditators than in controls was replicated in an independent dataset. These findings suggest that yoga and meditation practitioners have stronger functional connectivity within basal ganglia cortico-thalamic feedback loops than non practitioners. Although we could not provide evidence for its mechanistic role, this greater connectivity might be related to the often reported effects of meditation and yoga on behavioral flexibility, mental health, and well-being. C1 [Gard, Tim; Hoelzel, Britta K.; Dickerson, Bradford C.; Lazar, Sara W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Gard, Tim] Univ Giessen, Bender Inst Neuroimaging, D-35390 Giessen, Germany. [Gard, Tim] Maastricht Univ, Fac Psychol & Neurosci, NL-6200 MD Maastricht, Netherlands. [Taquet, Maxime] Catholic Univ Louvain, Inst Informat & Commun Elect, Louvain La Neuve, Belgium. [Taquet, Maxime] Catholic Univ Louvain, Inst Appl Math, Louvain La Neuve, Belgium. [Dixit, Rohan] BrainBot, San Francisco, CA USA. [Hoelzel, Britta K.] Tech Univ Munich, Klinikum Rechts Isar, Dept Neuroradiol, D-80290 Munich, Germany. RP Gard, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. EM tgard@nmr.mgh.harvard.edu RI Lazar, Sara/G-3809-2012 OI Lazar, Sara/0000-0003-1126-8363 FU NIH [R21AT003673, K01AT00694, R01AT006344]; Kripalu Institute for Extraordinary Living; Shared Instrumentation Grants [1S10RR023401, S10RR019307, 1S10RR023043] FX This study was funded by NIH award R21AT003673, K01AT00694, and R01AT006344, and awards from the Kripalu Institute for Extraordinary Living, Sarah Hancock, and Jeff Walker. The project was made possible by the resources provided by Shared Instrumentation Grants 1S10RR023401, S10RR019307, and 1S10RR023043. We also would like to thank all participants for their contribution. NR 72 TC 2 Z9 2 U1 6 U2 33 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD MAR 16 PY 2015 VL 9 AR UNSP 137 DI 10.3339/fnhum.2015.DD137 PG 12 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA CF3XJ UT WOS:000352482100001 PM 25852521 ER PT J AU Pereira, RC Juppner, H Gales, B Salusky, IB Wesseling-Perry, K AF Pereira, Renata C. Jueppner, Harald Gales, Barbara Salusky, Isidro B. Wesseling-Perry, Katherine TI Osteocytic Protein Expression Response to Doxercalciferol Therapy in Pediatric Dialysis Patients SO PLOS ONE LA English DT Article ID GROWTH-FACTOR 23; DENTIN MATRIX PROTEIN-1; CHRONIC KIDNEY-DISEASE; C-TERMINAL FRAGMENT; PARATHYROID-HORMONE; SECONDARY HYPERPARATHYROIDISM; PHOSPHATE HOMEOSTASIS; RENAL OSTEODYSTROPHY; BREAST-CARCINOMA; GENE-EXPRESSION AB Background Osteocytic protein expression is dysregulated in CKD and is affected by changes in mineral metabolism; however the effects of active vitamin D sterol therapy on osteocyte protein expression in advanced CKD is unknown. Methods Eleven pediatric patients with end stage kidney disease underwent bone biopsy, were treated for 8 months with doxercalciferol, and then underwent a second bone biopsy. Bone expression of fibroblast growth factor 23 (FGF23), dentin matrix protein 1 (DMP1), and sclerostin were determined by immunohistochemistry and quantified by Ariol Scanning. Western blot analysis and qRT-PCR was performed on bone abstracts of a subset of study subjects to determine the nature (i.e. size) of FGF23 and DMP1 in bone before and after therapy. Results As assessed by immunohistochemistry, bone FGF23, DMP1 and sclerostin protein all increased with therapy. In the case of FGF23, this increase was due to an increase in the full-length molecule without the appearance of FGF23 fragments. DMP1 was present primarily in its full-length formin healthy controls while 57kDa and 37kDa fragments of DMP1 were apparent in bone of dialysis patients at baseline and the 57 kDa appeared to decrease with therapy. Conclusion Marked changes in osteocytic protein expression accompany doxercalciferol therapy, potentially impacting bone mineralization and the skeletal response to PTH. The effects of these bone changes on long-term outcomes remain to be determined. C1 [Pereira, Renata C.; Gales, Barbara; Salusky, Isidro B.; Wesseling-Perry, Katherine] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA USA. RP Wesseling-Perry, K (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. EM kwesseling@mednet.ucla.edu FU USPHS [DK-67563, DK-35423, DK-080984, PO-1DK11794]; CTSI [UL1 TR-000124]; Casey Lee Ball Foundation FX This work was supported in part by USPHS grants DK-67563, DK-35423, DK-080984, PO-1DK11794, and CTSI grant UL1 TR-000124 and funds from the Casey Lee Ball Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 6 Z9 6 U1 2 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 16 PY 2015 VL 10 IS 3 AR e0120856 DI 10.1371/journal.pone.0120856 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CD6EY UT WOS:000351183500195 PM 25774916 ER PT J AU Kim, DK Lee, J Kim, SR Choi, DS Yoon, YJ Kim, JH Go, G Nhung, D Hong, K Jang, SC Kim, SH Park, KS Kim, OY Park, HT Seo, JH Aikawa, E Baj-Krzyworzeka, M van Balkom, BWM Belting, M Blanc, L Bond, V Bongiovanni, A Borras, FE Buee, L Buzas, EI Cheng, L Clayton, A Cocucci, E Dela Cruz, CS Desiderio, DM Di Vizio, D Ekstrom, K Falcon-Perez, JM Gardiner, C Giebel, B Greening, DW Gross, JC Gupta, D Hendrix, A Hill, AF Hill, MM Hoen, EN Hwang, DW Inal, J Jagannadham, MV Jayachandran, M Jee, YK Jorgensen, M Kim, KP Kim, YK Kislinger, T Lasser, C Lee, DS Lee, H van Leeuwen, J Lener, T Liu, ML Lotvall, J Marcilla, A Mathivanan, S Moller, A Morhayim, J Mullier, F Nazarenko, I Nieuwland, R Nunes, DN Pang, K Park, J Patel, T Pocsfalvi, G del Portillo, H Putz, U Ramirez, MI Rodrigues, ML Roh, TY Royo, F Sahoo, S Schiffelers, R Sharma, S Siljander, P Simpson, RJ Soekmadji, C Stahl, P Stensballe, A Stepien, E Tahara, H Trummer, A Valadi, H Vella, LJ Wai, SN Witwer, K Yanez-Mo, M Youn, H Zeidler, R Gho, YS AF Kim, Dae-Kyum Lee, Jaewook Kim, Sae Rom Choi, Dong-Sic Yoon, Yae Jin Kim, Ji Hyun Go, Gyeongyun Nhung, Dinh Hong, Kahye Jang, Su Chul Kim, Si-Hyun Park, Kyong-Su Kim, Oh Youn Park, Hyun Taek Seo, Ji Hye Aikawa, Elena Baj-Krzyworzeka, Monika van Balkom, Bas W. M. Belting, Mattias Blanc, Lionel Bond, Vincent Bongiovanni, Antonella Borras, Francesc E. Buee, Luc Buzas, Edit I. Cheng, Lesley Clayton, Aled Cocucci, Emanuele Dela Cruz, Charles S. Desiderio, Dominic M. Di Vizio, Dolores Ekstrom, Karin Falcon-Perez, Juan M. Gardiner, Chris Giebel, Bernd Greening, David W. Gross, Julia Christina Gupta, Dwijendra Hendrix, An Hill, Andrew F. Hill, Michelle M. Hoen, Esther Nolte-'t Hwang, Do Won Inal, Jameel Jagannadham, Medicharla V. Jayachandran, Muthuvel Jee, Young-Koo Jorgensen, Malene Kim, Kwang Pyo Kim, Yoon-Keun Kislinger, Thomas Lasser, Cecilia Lee, Dong Soo Lee, Hakmo van Leeuwen, Johannes Lener, Thomas Liu, Ming-Lin Lotvall, Jan Marcilla, Antonio Mathivanan, Suresh Moeller, Andreas Morhayim, Jess Mullier, Francois Nazarenko, Irina Nieuwland, Rienk Nunes, Diana N. Pang, Ken Park, Jaesung Patel, Tushar Pocsfalvi, Gabriella del Portillo, Hernando Putz, Ulrich Ramirez, Marcel I. Rodrigues, Marcio L. Roh, Tae-Young Royo, Felix Sahoo, Susmita Schiffelers, Raymond Sharma, Shivani Siljander, Pia Simpson, Richard J. Soekmadji, Carolina Stahl, Philip Stensballe, Allan Stepien, Ewa Tahara, Hidetoshi Trummer, Arne Valadi, Hadi Vella, Laura J. Wai, Sun Nyunt Witwer, Kenneth Yanez-Mo, Maria Youn, Hyewon Zeidler, Reinhard Gho, Yong Song TI EVpedia: a community web portal for extracellular vesicles research SO BIOINFORMATICS LA English DT Article ID MEMBRANE-VESICLES; PROTEOMIC ANALYSIS; EXOSOMES; MICROPARTICLES; CANCER; CELLS; DELIVERY; PLASMA; PROSTASOMES; EXPRESSION AB Motivation: Extracellular vesicles (EVs) are spherical bilayered proteolipids, harboring various bioactive molecules. Due to the complexity of the vesicular nomenclatures and components, online searches for EV-related publications and vesicular components are currently challenging. Results: We present an improved version of EVpedia, a public database for EVs research. This community web portal contains a database of publications and vesicular components, identification of orthologous vesicular components, bioinformatic tools and a personalized function. EVpedia includes 6879 publications, 172 080 vesicular components from 263 high-throughput datasets, and has been accessed more than 65 000 times from more than 750 cities. In addition, about 350 members from 73 international research groups have participated in developing EVpedia. This free web-based database might serve as a useful resource to stimulate the emerging field of EV research. C1 [Kim, Dae-Kyum; Lee, Jaewook; Kim, Sae Rom; Choi, Dong-Sic; Kim, Ji Hyun; Go, Gyeongyun; Nhung, Dinh; Hong, Kahye; Jang, Su Chul; Kim, Si-Hyun; Park, Kyong-Su; Kim, Oh Youn; Park, Hyun Taek; Seo, Ji Hye; Roh, Tae-Young; Gho, Yong Song] Pohang Univ Sci & Technol, Dept Life Sci, Pohang, South Korea. [Yoon, Yae Jin; Roh, Tae-Young] Pohang Univ Sci & Technol, Div Integrat Biosci & Biotechnol, Pohang, South Korea. [Aikawa, Elena] Harvard Univ, Sch Med, Brigham & Womens Hosp, Cardiovasc Med, Boston, MA USA. [Baj-Krzyworzeka, Monika] Jagiellonian Univ, Coll Med, Polish Amer Inst Paediat, Dept Clin Immunol, Krakow, Poland. [van Balkom, Bas W. M.] Univ Med Ctr Utrecht, Dept Hypertens & Nephrol, Utrecht, Netherlands. [Belting, Mattias] Lund Univ, Dept Clin Sci, Sect Oncol, Lund, Sweden. [Blanc, Lionel] Feinstein Inst Med Res, Manhasset, NY USA. [Bond, Vincent] Morehouse Sch Med, Dept Microbiol Biochem & Immunol, Atlanta, GA 30310 USA. [Bongiovanni, Antonella] CNR, Inst Biomed & Mol Immunol IBIM, Palermo, Italy. [Borras, Francesc E.] Germans Trias & Pujol Univ Hosp, Germans Trias & Pujol Res Inst, Innovat Vesicles & Cells Applicat Therapy, Badalona, Spain. [Buee, Luc] INSERM, JEAN PIERRE Aubert Res Ctr, UMR837, F-59045 Lille, France. [Buzas, Edit I.] Semmelweis Univ, Dept Genet Cell & Immunobiol, H-1085 Budapest, Hungary. [Cheng, Lesley; Hill, Andrew F.] Univ Melbourne, Dept Biochem & Mol Biol, Mol Sci & Biotechnol Inst BIO21, Melbourne, Vic, Australia. [Clayton, Aled] Cardiff Univ, Sch Med, Velindre Canc Ctr, Inst Canc & Genet, Cardiff CF10 3AX, S Glam, Wales. [Cocucci, Emanuele] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Cocucci, Emanuele] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Dela Cruz, Charles S.] Yale Univ, Sch Med, Dept Internal Med, Sect Pulm Crit Care & Sleep Med, New Haven, CT 06510 USA. [Desiderio, Dominic M.] Univ Tennessee, Hlth Sci Ctr, Coll Med, Dept Neurol, Memphis, TN USA. [Di Vizio, Dolores] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Canc Biol Program, Los Angeles, CA 90048 USA. [Ekstrom, Karin] Univ Gothenburg, Inst Clin Sci, Dept Biomat, Sahlgrenska Acad, Gothenburg, Sweden. [Ekstrom, Karin] BIOMATCELL VINN Excellence Ctr Biomat & Cell Ther, Gothenburg, Sweden. [Falcon-Perez, Juan M.; Royo, Felix] IKERBASQUE Res Fdn, Metabol Unit, CIC BioGUNE, Derio, Bizkaia, Spain. [Gardiner, Chris] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Oxford, England. [Giebel, Bernd] Univ Duisburg Essen, Univ Hosp Essen, Inst Transfus Med, Essen, Germany. [Greening, David W.; Mathivanan, Suresh; Simpson, Richard J.] La Trobe Univ, La Trobe Inst Mol Sci LIMS, Melbourne, Vic, Australia. [Gross, Julia Christina] German Canc Res Ctr, Div Signaling & Funct Genom, Heidelberg, Germany. [Gupta, Dwijendra] Jai Prakash Univ, Chapra, Bihar, India. [Hendrix, An] Ghent Univ Hosp, Dept Radiat Oncol & Expt Canc Res, Lab Expt Canc Res, Ghent, Belgium. [Hill, Michelle M.] Univ Queensland, Translat Res Inst, Diamantina Inst, Brisbane, Qld, Australia. [Hoen, Esther Nolte-'t] Univ Utrecht, Fac Vet Med, Dept Biochem & Cell Biol, Utrecht, Netherlands. [Hwang, Do Won; Lee, Dong Soo; Youn, Hyewon] Seoul Natl Univ, Coll Med, Dept Nucl Med, Seoul, South Korea. [Inal, Jameel] London Metropolitan Univ, Fac Life Sci & Comp, Cellular & Mol Immunol Res Ctr, London, England. [Jagannadham, Medicharla V.] CSIR, Ctr Cellular & Mol Biol, Hyderabad, Andhra Pradesh, India. [Jayachandran, Muthuvel] Mayo Clin, Dept Physiol & Biomed Engn, Rochester, MN USA. [Jee, Young-Koo] Dankook Univ, Coll Med, Dept Internal Med, Cheonan, South Korea. [Jorgensen, Malene] Aalborg Univ Hosp, Dept Clin Immunol, Aalborg, Denmark. [Kim, Kwang Pyo] Kyung Hee Univ, Dept Appl Chem, Yongin, South Korea. [Kim, Yoon-Keun] Ewha Womans Univ, Med Ctr, Seoul, South Korea. [Kislinger, Thomas] Ontario Canc Inst, Toronto, ON M4X 1K9, Canada. [Lasser, Cecilia; Lotvall, Jan] Univ Gothenburg, Sahlgrenska Acad, Krefting Res Ctr, Gothenburg, Sweden. [Lee, Hakmo] Seoul Natl Univ Hosp, Biomed Res Inst, Seoul 110744, South Korea. [van Leeuwen, Johannes; Morhayim, Jess] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands. [Lener, Thomas] Paracelsus Med Univ, Univ Hosp Salzburg, Dept Blood Grp Serol & Transfus Med, Salzburg, Austria. [Lener, Thomas] Paracelsus Med Univ, Spinal Cord Injury & Tissue Regenerat Ctr Salzbur, Salzburg, Austria. [Liu, Ming-Lin] Univ Penn, Dept Dermatol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Liu, Ming-Lin] Temple Univ, Sch Med, Dept Med, Philadelphia, PA 19122 USA. [Marcilla, Antonio] Univ Valencia, Dept Biol Celular & Parasitol, Area Parasitol, Valencia, Spain. [Moeller, Andreas] QIMR Berghofer Med Res Inst, Tumour Microenvironm Lab, Herston, Qld, Australia. [Mullier, Francois] Catholic Univ Louvain, Hematol Lab, Namur Thrombosis & Hemostasis Ctr, NARILIS,CHU Dinant Godinne UCL Namur, Louvain, Belgium. [Mullier, Francois] Univ Namur, Dept Pharm, NARILIS, Namur Thrombosis & Hemostasis Ctr, Naumr, Belgium. [Nazarenko, Irina] Med Ctr Univ Freiburg, Inst Environm Hlth Sci, Freiburg, Germany. [Nazarenko, Irina] Med Ctr Univ Freiburg, Hosp Infect Control, Freiburg, Germany. [Nieuwland, Rienk] Univ Amsterdam, Acad Med Ctr, Dept Clin Chem, NL-1105 AZ Amsterdam, Netherlands. [Nunes, Diana N.] AC Camargo Canc Ctr, Lab Med Genom, Sao Paulo, Brazil. [Pang, Ken] Walter & Eliza Hall Inst Med Res, Inflammat Div, Parkville, Vic, Australia. [Pang, Ken] Univ Melbourne, Dept Paediat, Parkville, Vic 3052, Australia. [Park, Jaesung] Pohang Univ Sci & Technol, Dept Mech Engn, Pohang, South Korea. [Patel, Tushar] Mayo Clin, Dept Transplantat & Canc Biol, Jacksonville, FL 32224 USA. [Pocsfalvi, Gabriella] Natl Res Council Italy, Mass Spectrometry & Prote, Inst Biosci & Bior, Naples, Italy. [del Portillo, Hernando] Barcelona Ctr Int Hlth Res, ICREA, Barcelona, Spain. [Putz, Ulrich] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Melbourne, Vic, Australia. [Ramirez, Marcel I.] Fundacao Oswaldo Cruz, Lab Mol Biol Parasites & Vectors, Rio De Janeiro, Brazil. [Rodrigues, Marcio L.] Univ Fed Rio de Janeiro, Paulo Goes Microbiol Inst, Rio De Janeiro, Brazil. [Rodrigues, Marcio L.] Fundacao Oswaldo Cruz, Ctr Technol Dev Hlth CDTS, Rio De Janeiro, Brazil. [Sahoo, Susmita] Icahn Sch Med Mt Sinai, Cardiovasc Res Inst, New York, NY 10029 USA. [Schiffelers, Raymond] Univ Med Ctr Utrecht, Dept Clin Chem & Hematol, Utrecht, Netherlands. [Sharma, Shivani] Univ Calif Los Angeles, Calif Nanosyst Inst, Los Angeles, CA USA. [Siljander, Pia] Univ Helsinki, Dept Biosci, Div Biochem & Biotechnol, Helsinki, Finland. [Soekmadji, Carolina] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Australian Prostate Canc Res Ctr Queensland, Brisbane, Qld 4001, Australia. [Stahl, Philip] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. [Stensballe, Allan] Aalborg Univ, Dept Hlth Sci & Technol, Aalborg, Denmark. [Stepien, Ewa] Jagiellonian Univ, Dept Med Phys, Krakow, Poland. [Tahara, Hidetoshi] Hiroshima Univ, Grad Sch Biomed Sci, Dept Cellular & Mol Biol, Hiroshima, Japan. [Trummer, Arne] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, Hannover, Germany. [Valadi, Hadi] Univ Gothenburg, Sahlgrenska Acad, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden. [Vella, Laura J.] Austin Hosp, Ludwig Inst Canc Res Melbourne, Heidelberg, Vic 3084, Australia. [Wai, Sun Nyunt] Umea Univ, Dept Mol Biol, Umea, Sweden. [Witwer, Kenneth] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD USA. [Yanez-Mo, Maria] Inst Invest Sanitaria Princesa, Hosp Santa Cristina, Unidad Invest, Madrid, Spain. [Zeidler, Reinhard] Univ Munich, Dept Otorhinolaryngol, Helmholtz Zentrum Munchen, Munich, Germany. [Zeidler, Reinhard] Univ Munich, Res Grp Gene Vectors, Helmholtz Zentrum Munchen, Munich, Germany. RP Gho, YS (reprint author), Pohang Univ Sci & Technol, Dept Life Sci, Pohang, South Korea. EM ysgho@postech.ac.kr RI Inal, Jameel/G-2995-2010; Nazarenko, Irina/E-5714-2010; Witwer, Kenneth/G-1626-2013; Rodrigues, Marcio/J-3727-2013; BUEE, Luc/B-3126-2010; Hill, Andrew/B-4527-2009; Hill, Michelle M/G-4417-2010; Mathivanan, Suresh/D-2045-2009; Trummer, Arne/J-5203-2015; Nunes, Diana/A-7867-2010; marcilla, antonio/F-9996-2010; Moller, Andreas/O-1063-2015; patel, tushar/J-3976-2013; Royo, Felix/A-7198-2015; Greening, David/E-9138-2016; Falcon-Perez, Juan/F-5920-2011 OI Blanc, Lionel/0000-0002-0185-6260; Stepien, Ewa/0000-0003-3589-1715; Vella, Laura/0000-0002-1869-6291; Gardiner, Chris/0000-0002-2318-0062; Mullier, Francois/0000-0001-6947-6099; Jang, Su Chul/0000-0003-3326-1007; Siljander, Pia/0000-0003-2326-5821; Inal, Jameel/0000-0002-7200-0363; Lotvall, Jan/0000-0001-9195-9249; Jee, Young-Koo/0000-0001-5800-8038; Pocsfalvi, Gabriella/0000-0001-6065-3853; Yanez-Mo, Maria/0000-0001-7484-2866; bongiovanni, antonella/0000-0002-0307-4043; Choi, Dong-Sic/0000-0002-2516-5616; Youn, Hyewon/0000-0003-1006-2689; Falcon-Perez, Juan M/0000-0003-3133-0670; Ekstrom, Karin/0000-0001-7808-4572; BORRAS, FRANCESC E./0000-0003-4038-1912; Witwer, Kenneth/0000-0003-1664-4233; Rodrigues, Marcio/0000-0002-6081-3439; BUEE, Luc/0000-0002-6261-4230; Hill, Andrew/0000-0001-5581-2354; Hill, Michelle M/0000-0003-1134-0951; Mathivanan, Suresh/0000-0002-7290-5795; marcilla, antonio/0000-0003-0004-0531; patel, tushar/0000-0001-7021-9532; Royo, Felix/0000-0001-9769-4165; FU National Research Foundation of Korea (NRF) grant - Korea government (MSIP) [2014-023004]; Ministry of Health and Welfare grant - Korea government [A120273]; KRIBB Research Initiative Program; National Junior Research Fellowship [2014-048579]; BK21 PLUS program - Ministry of Education, Science and Technology, Republic of Korea [10Z20130012243] FX This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) [No. 2014-023004], the Ministry of Health and Welfare grant funded by the Korea government [No. A120273] and a grant from KRIBB Research Initiative Program. D.-K. K is supported by a National Junior Research Fellowship [No. 2014-048579] and Y. J. Y by BK21 PLUS program [10Z20130012243] funded by Ministry of Education, Science and Technology, Republic of Korea. NR 49 TC 41 Z9 42 U1 10 U2 39 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 MAR 15 PY 2015 VL 31 IS 6 BP 933 EP 939 DI 10.1093/bioinformatics/btu741 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 CF0XW UT WOS:000352268900018 PM 25388151 ER PT J AU Volz, MS Suarez-Contreras, V Portilla, ALS Fregni, F AF Volz, Magdalena Sarah Suarez-Contreras, Vanessa Portilla, Andrea L. Santos Fregni, Felipe TI Mental imagery-induced attention modulates pain perception and cortical excitability SO BMC NEUROSCIENCE LA English DT Article DE Pain; Attention; Mental imagery; Pain catastrophizing; Cortical excitability ID TRANSCRANIAL MAGNETIC STIMULATION; PHANTOM LIMB PAIN; MOTOR CORTEX DISINHIBITION; NEUROPATHIC PAIN; PURDUE PEGBOARD; INTRACORTICAL INHIBITION; EVOKED-POTENTIALS; MYOFASCIAL PAIN; NORMATIVE DATA; SILENT PERIOD AB Background: Mental imagery is a powerful method of altering brain activity and behavioral outcomes, such as performance of cognition and motor skills. Further, attention and distraction can modulate pain-related neuronal networks and the perception of pain. This exploratory study examined the effects of mental imagery-induced attention on pressure pain threshold and cortical plasticity using transcranial magnetic stimulation (TMS). This blinded, randomized, and parallel-design trial comprised 30 healthy right-handed male subjects. Exploratory statistical analyses were performed using ANOVA and t-tests for pain and TMS assessments. Pearson's correlation was used to analyze the association between changes in pain threshold and cortical excitability. Results: In the analysis of pain outcomes, there was no significant interaction effect on pain between group versus time. In an exploratory analysis, we only observed a significant effect of group for the targeted left hand (ANOVA with pain threshold as the dependent variable and time and group as independent variables). Although there was only a within-group effect of mental imagery on pain, further analyses showed a significant positive correlation of changes in pain threshold and cortical excitability (motor-evoked potentials via TMS). Conclusions: Mental imagery has a minor effect on pain modulation in healthy subjects. Its effects appear to differ compared with chronic pain, leading to a small decrease in pain threshold. Assessments of cortical excitability confirmed that these effects are related to the modulation of pain-related cortical circuits. These exploratory findings suggest that neuronal plasticity is influenced by pain and that the mental imagery effects on pain depend on the state of central sensitization. C1 [Volz, Magdalena Sarah; Suarez-Contreras, Vanessa; Portilla, Andrea L. Santos; Fregni, Felipe] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil,Lab Neuromodulat, Boston, MA 02114 USA. [Volz, Magdalena Sarah; Suarez-Contreras, Vanessa; Portilla, Andrea L. Santos; Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Volz, Magdalena Sarah] Charite, D-13353 Berlin, Germany. [Fregni, Felipe] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA USA. RP Fregni, F (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil,Lab Neuromodulat, 125 Nashua St 727, Boston, MA 02114 USA. EM fregni.felipe@mgh.harvard.edu FU NIH [1R21DK81773-1A1] FX This study was also supported by a NIH grant 1R21DK81773-1A1. NR 59 TC 3 Z9 3 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2202 J9 BMC NEUROSCI JI BMC Neurosci. PD MAR 15 PY 2015 VL 16 AR 15 DI 10.1186/s12868-015-0146-6 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CF0UE UT WOS:000352258900001 PM 25887060 ER PT J AU Chen, EJ Sowalsky, AG Gao, S Cai, CM Voznesensky, O Schaefer, R Loda, M True, LD Ye, HH Troncoso, P Lis, RL Kantoff, PW Montgomery, RB Nelson, PS Bubley, GJ Balk, SP Taplin, ME AF Chen, Eddy J. Sowalsky, Adam G. Gao, Shuai Cai, Changmeng Voznesensky, Olga Schaefer, Rachel Loda, Massimo True, Lawrence D. Ye, Huihui Troncoso, Patricia Lis, Rosina L. Kantoff, Philip W. Montgomery, Robert B. Nelson, Peter S. Bubley, Glenn J. Balk, Steven P. Taplin, Mary-Ellen TI Abiraterone Treatment in Castration-Resistant Prostate Cancer Selects for Progesterone Responsive Mutant Androgen Receptors SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-GROWTH; CELL-LINE; MUTATION; BICALUTAMIDE; PROGRESSION; EXPRESSION; STEROIDOGENESIS; TESTOSTERONE; DUTASTERIDE; INHIBITORS AB Purpose: The CYP17A1 inhibitor abiraterone markedly reduces androgen precursors and is thereby effective in castration-resistant prostate cancer (CRPC). However, abiraterone increases progesterone, which can activate certain mutant androgen receptors (AR) identified previously in flutamide-resistant tumors. Therefore, we sought to determine if CYP17A1 inhibitor treatment selects for progesterone-activated mutant ARs. Experimental Design: AR was examined by targeted sequencing in metastatic tumor biopsies from 18 patients with CRPC who were progressing on a CYP17A1 inhibitor (17 on abiraterone, 1 on ketoconazole), alone or in combination with dutasteride, and by whole-exome sequencing in residual tumor in one patient treated with neoadjuvant leuprolide plus abiraterone. Results: The progesterone-activated T878A-mutant AR was present at high allele frequency in 3 of the 18 CRPC cases. It was also present in one focus of resistant tumor in the neoadjuvant-treated patient, but not in a second clonally related resistant focus that instead had lost one copy of PTEN and both copies of CHD1. The T878A mutation appeared to be less common in the subset of patients with CRPC treated with abiraterone plus dutasteride, and transfection studies showed that dutasteride was a more potent direct antagonist of the T878A versus the wild-type AR. Conclusions: These findings indicate that selection for tumor cells expressing progesterone-activated mutant ARs is a mechanism of resistance to CYP17A1 inhibition. (C) 2014 AACR. C1 [Chen, Eddy J.; Sowalsky, Adam G.; Gao, Shuai; Cai, Changmeng; Voznesensky, Olga; Schaefer, Rachel; Ye, Huihui; Bubley, Glenn J.; Balk, Steven P.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Loda, Massimo; Lis, Rosina L.; Kantoff, Philip W.; Taplin, Mary-Ellen] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [True, Lawrence D.; Montgomery, Robert B.; Nelson, Peter S.] Univ Washington, Seattle, WA 98195 USA. [Troncoso, Patricia] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Nelson, Peter S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Balk, SP (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02115 USA. EM sbalk@bidmc.harvard.edu; mary_taplin@dfci.harvard.edu RI Sowalsky, Adam/K-1485-2013; OI Sowalsky, Adam/0000-0003-2760-1853; Cai, Changmeng/0000-0002-8701-2586 FU NIH [P01 CA163227, K99 CA166507, SPORE P50 CA090381, SPORE P50 CA097186, T32 CA081156]; Department of Defense Prostate Cancer Research Program [W81XWH 13 1 0267, W81XWH 11 1 0295, W81XWH 10 1 0590, W81XWH 08-1-0414, W81XWH-07-1-0443]; DF/HCC Mazzone Award; Prostate Cancer Foundation; Ortho Biotech Oncology Research and Development (unit of Cougar Biotechnology, now Janssen Research Development) FX This work was supported by grants from the NIH (P01 CA163227, K99 CA166507, Dana-Farber/Harvard Cancer Center SPORE P50 CA090381, Pacific Northwest Prostate Cancer SPORE P50 CA097186, and T32 CA081156), the Department of Defense Prostate Cancer Research Program (W81XWH 13 1 0267, W81XWH 11 1 0295, W81XWH 10 1 0590, W81XWH 08-1-0414, and W81XWH-07-1-0443), a DF/HCC Mazzone Award, and by generous support through Challenge Awards from the Prostate Cancer Foundation. The abiraterone clinical trials were supported by Ortho Biotech Oncology Research and Development (unit of Cougar Biotechnology, now Janssen Research & Development). NR 31 TC 43 Z9 43 U1 3 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 15 PY 2015 VL 21 IS 6 BP 1273 EP 1280 DI 10.1158/1078-0432.CCR-14-1220 PG 8 WC Oncology SC Oncology GA CE8DJ UT WOS:000352071200007 PM 25320358 ER PT J AU Heidari, P Deng, F Esfahani, SA Leece, AK Shoup, TM Vasdev, N Mahmood, U AF Heidari, Pedram Deng, Francis Esfahani, Shadi A. Leece, Alicia K. Shoup, Timothy M. Vasdev, Neil Mahmood, Umar TI Pharmacodynamic Imaging Guides Dosing of a Selective Estrogen Receptor Degrader SO CLINICAL CANCER RESEARCH LA English DT Article ID ADVANCED BREAST-CANCER; POSITRON-EMISSION-TOMOGRAPHY; POSTMENOPAUSAL WOMEN; ENDOCRINE THERAPY; PHASE-II; ANTIESTROGEN ICI-182780; AROMATASE INHIBITORS; HORMONE SENSITIVITY; PRECLINICAL MODEL; DOUBLE-BLIND AB Purpose: Estrogen receptor (ER) targeting is key in management of receptor-positive breast cancer. Currently, there are no methods to optimize anti-ER therapy dosing. This study assesses the use of 16 alpha-F-18-fluoroestradiol (F-18-FES) PET for fulvestrant dose optimization in a preclinical ER+ breast cancer model. Experimental Design: In vitro, F-18-FES retention was compared with ER alpha protein expression (ELISA) and ESR1 mRNA transcription (qPCR) in MCF7 cells (ER+) after treatment with different fulvestrant doses. MCF7 xenografts were grown in ovariectomized nude mice and assigned to vehicle, low-(0.05 mg), medium-(0.5 mg), or high-dose (5 mg) fulvestrant treatment groups (5-7 per group). Two and 3 days after fulvestrant treatment, PET/CT was performed using F-18-FES and F-18-FDG, respectively. ER expression was assessed by immunohistochemistry, ELISA, and qPCR on xenografts. Tumor proliferation was assessed using Ki67 immunohistochemistry. Results: In vitro, we observed a parallel graded reduction in F-18-FES uptake and ER expression with increased fulvestrant doses, despite enhancement of ER mRNA transcription. In xenografts, ER expression significantly decreased with increased fulvestrant dose, despite similar mRNA expression and Ki67 staining among the treatment groups. We observed a significant dose-dependent reduction of F-18-FES PET mean standardized uptake value (SUVmean) with fulvestrant treatment but no significant difference among the treatment groups in F-18-FDG PET SUVmean. Conclusions: We demonstrated that F-18-FES uptake mirrors the dose-dependent changes in functional ER expression with fulvestrant resulting in ER degradation and/or blockade; these precede changes in tumor metabolism and proliferation. Quantitative F-18-FES PET may be useful for tracking early efficacy of ER blockade/degradation and guiding ER-targeted therapy dosing in patients with breast cancer. (C)2015 AACR. C1 [Heidari, Pedram; Deng, Francis; Esfahani, Shadi A.; Leece, Alicia K.; Mahmood, Umar] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Deng, Francis] Washington Univ, Sch Med, St Louis, MO USA. [Shoup, Timothy M.; Vasdev, Neil] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. EM umahmood@mgh.harvard.edu OI Deng, Francis/0000-0003-3117-5076 FU Society for Nuclear Medicine and Molecular Imaging; Washington University School of Medicine Dean's Fellowship; [U01CA084301]; [P50CA127003] FX This work was supported by U01CA084301 and P50CA127003. F. Deng supported by a Bradley-Alavi Student Fellowship from the Society for Nuclear Medicine and Molecular Imaging and a Washington University School of Medicine Dean's Fellowship. NR 39 TC 8 Z9 8 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 MAR 15 PY 2015 VL 21 IS 6 BP 1340 EP 1347 DI 10.1158/1078-0432.CCR-14-1178 PG 8 WC Oncology SC Oncology GA CE8DJ UT WOS:000352071200015 PM 25609068 ER PT J AU Li, YY Hanna, GJ Laga, AC Haddad, RI Lorch, JH Hammerman, PS AF Li, Yvonne Y. Hanna, Glenn J. Laga, Alvaro C. Haddad, Robert I. Lorch, Jochen H. Hammerman, Peter S. TI Genomic Analysis of Metastatic Cutaneous Squamous Cell Carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID ORGAN-TRANSPLANT RECIPIENTS; GROWTH-FACTOR-RECEPTOR; COPY-NUMBER ALTERATION; NF-KAPPA-B; RAS MUTATIONS; SKIN-CANCER; LUNG ADENOCARCINOMA; SOMATIC MUTATIONS; CARD11 MUTATIONS; POINT MUTATIONS AB Purpose: A rare 5% of cutaneous squamous cell carcinomas (cSCC) metastasize, lack FDA-approved therapies, and carry a poor prognosis. Our aim was to identify recurrent genomic alterations in this little-studied population of metastatic cSCCs. Experimental Design: We performed targeted sequencing of 504 cancer-associated genes on lymph node metastases in 29 patients with cSCC and identified mutations and somatic copy-number alterations associated with metastatic cSCC. We determined significantly mutated, deleted, and amplified genes and associated genomic alterations with clinical variables. Results: The cSCC genome is heterogeneous with widely varying numbers of genomic alterations and does not appear to be associated with human papillomavirus. We found previously identified recurrently altered genes (TP53, CDKN2A, NOTCH1/2) but also a wide spectrum of oncogenic mutations affecting RAS/RTK/PI3K, squamous differentiation, cell cycle, and chromatin remodeling pathway genes. Specific mutations in known oncogenic drivers and pathways were correlated with inferior patient outcomes. Our results suggest potential therapeutic targets in metastatic cSCC, including PIK3CA, FGFR3, BRAF, and EGFR, similar to those reported in SCCs of the lung and head and neck, suggesting that clinical trials could be developed to accrue patients with SCCs from multiple sites of origin. Conclusions: We have genomically characterized a rare cohort of 29 metastatic cSCCs and identified a diverse array of oncogenic alterations that can guide future studies of this disease. (C) 2015 AACR. C1 [Li, Yvonne Y.; Haddad, Robert I.; Lorch, Jochen H.; Hammerman, Peter S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Li, Yvonne Y.] Broad Inst, Cambridge, MA USA. [Hanna, Glenn J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Laga, Alvaro C.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Haddad, Robert I.; Lorch, Jochen H.; Hammerman, Peter S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Haddad, Robert I.; Lorch, Jochen H.; Hammerman, Peter S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Hammerman, PS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Jochen_Lorch@dfci.harvard.edu; Peter_Hammerman@dfci.harvard.edu FU NCI [K08 CA163677]; Friends of Dana Farber Grant FX P.S. Hammerman is supported by NCI K08 CA163677. J.H. Lorch is supported by a Friends of Dana Farber Grant. NR 65 TC 27 Z9 27 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 15 PY 2015 VL 21 IS 6 BP 1447 EP 1456 DI 10.1158/1078-0432.CCR-14-1773 PG 10 WC Oncology SC Oncology GA CE8DJ UT WOS:000352071200026 PM 25589618 ER PT J AU Rodrigues, LU Rider, L Nieto, C Romero, L Karimpour-Fard, A Loda, M Lucia, MS Wu, M Shi, LH Cimic, A Sirintrapun, SJ Nolley, R Pac, C Chen, HT Peehl, DM Xu, JF Liu, WN Costello, JC Cramer, SD AF Rodrigues, Lindsey Ulkus Rider, Leah Nieto, Cera Romero, Lina Karimpour-Fard, Anis Loda, Massimo Lucia, M. Scott Wu, Min Shi, Lihong Cimic, Adela Sirintrapun, S. Joseph Nolley, Rosalie Pac, Colton Chen, Haitao Peehl, Donna M. Xu, Jianfeng Liu, Wennuan Costello, James C. Cramer, Scott D. TI Coordinate Loss of MAP3K7 and CHD1 Promotes Aggressive Prostate Cancer SO CANCER RESEARCH LA English DT Article ID MEDIATED CELL-ADHESION; I-KAPPA-B; MESENCHYMAL TRANSITION; E-CADHERIN; PSA RECURRENCE; KINASE TAK1; EXPRESSION; CARCINOMA; PATHWAY; NEUROENDOCRINE AB Prostate cancer subtypes are poorly defined and functional validation of drivers of ETS rearrangement-negative prostate cancer has not been conducted. Here, we identified an ETS- subtype of aggressive prostate cancer (ERG-MAP3K7(dcl)CHD1(dcl)) and used a novel developmental model and a cell line xenograft model to show that cosuppression of MAP3K7 and CHD1 expression promotes aggressive disease. Analyses of publicly available prostate cancer datasets revealed that MAP3K7 and CHD1 were significantly codeleted in 10% to 20% of localized tumors and combined loss correlated with poor disease-free survival. To evaluate the functional impact of dual MAP3K7-CHD1 loss, we suppressed Map3k7 and/or Chd1 expression in mouse prostate epithelial progenitor/stem cells (PrP/SC) and performed tissue recombination experiments in vivo. Dual shMap3k7-shChd1 PrP/SC recombinants displayed massive glandular atypia with regions of prostatic intraepithelial neoplasia and carcinoma apparent. Combined Map3k7-Chd1 suppression greatly disrupted normal prostatic lineage differentiation; dual recombinants displayed significant androgen receptor loss, increased neuroendocrine differentiation, and increased neural differentiation. Clinical samples with dual MAP3K7-CHD1 loss also displayed neuroendocrine and neural characteristics. In addition, dual Map3k7-Chd1 suppression promoted E-cadherin loss and mucin production in recombinants. MAP3K7 and CHD1 protein loss also correlated with Gleason grade and E-cadherin loss in clinical samples. To further validate the phenotype observed in the PrP/SC model, we suppressed MAP3K7 and/or CHD1 expression in LNCaP prostate cancer cells. Dual shMAP3K7-shCHD1 LNCaP xenografts displayed increased tumor growth and decreased survival compared with shControl, shMAP3K7, and shCHD1 xenografts. Collectively, these data identify coordinate loss of MAP3K7 and CHD1 as a unique driver of aggressive prostate cancer development. C1 [Rodrigues, Lindsey Ulkus; Rider, Leah; Nieto, Cera; Romero, Lina; Karimpour-Fard, Anis; Wu, Min; Pac, Colton; Costello, James C.; Cramer, Scott D.] Univ Colorado, Dept Pharmacol, Aurora, CO 80045 USA. [Rodrigues, Lindsey Ulkus; Shi, Lihong] Wake Forest Univ, Dept Canc Biol, Winston Salem, NC 27109 USA. [Loda, Massimo] Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Lucia, M. Scott] Univ Colorado, Dept Pathol, Aurora, CO 80045 USA. [Cimic, Adela; Sirintrapun, S. Joseph] Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol, Winston Salem, NC 27103 USA. [Nolley, Rosalie; Peehl, Donna M.] Stanford Univ, Sch Med, Dept Urol, Stanford, CA 94305 USA. [Chen, Haitao] Fudan Univ, Ctr Genet Epidemiol, Shanghai 200433, Peoples R China. [Xu, Jianfeng; Liu, Wennuan] Wake Forest Univ, Ctr Canc Genom, Winston Salem, NC 27109 USA. [Xu, Jianfeng; Liu, Wennuan] Wake Forest Univ, Ctr Genom & Personalized Med Res, Winston Salem, NC 27109 USA. RP Cramer, SD (reprint author), Univ Colorado, Anschutz Med Campus,12801 East 17th Ave, Aurora, CO 80045 USA. EM scott.cramer@ucdenver.edu FU [R01 CA129418]; [W81XWH-12-10188] FX This study was supported by grant numbers R01 CA129418; W81XWH-12-10188. NR 49 TC 15 Z9 15 U1 0 U2 4 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 MAR 15 PY 2015 VL 75 IS 6 BP 1021 EP 1034 DI 10.1158/0008-5472.CAN-14-1596 PG 14 WC Oncology SC Oncology GA CE6IZ UT WOS:000351941400012 PM 25770290 ER PT J AU Spurgeon, ME Cheng, JW Bronson, RT Lambert, PF DeCaprio, JA AF Spurgeon, Megan E. Cheng, Jingwei Bronson, Roderick T. Lambert, Paul F. DeCaprio, James A. TI Tumorigenic Activity of Merkel Cell Polyomavirus T Antigens Expressed in the Stratified Epithelium of Mice SO CANCER RESEARCH LA English DT Article ID PAPILLOMAVIRUS TYPE-16 E7; TRANSGENIC MICE; MOUSE MODEL; GENE; CARCINOMAS; IDENTIFICATION; SKIN; CARCINOGENESIS; REPLICATION; PROGRESSION AB Merkel cell polyomavirus (MCPyV) is frequently associated with Merkel cell carcinoma (MCC), a highly aggressive neuroendocrine skin cancer. Most MCC tumors contain integrated copies of the viral genome with persistent expression of the MCPyV large T (LT) and small T (ST) antigen. MCPyV isolated from MCC typically contains wild-type ST but truncated forms of LT that retain the N-terminus but delete the C-terminus and render LT incapable of supporting virus replication. To determine the oncogenic activity of MCC tumor-derived T antigens in vivo, a conditional, tissue-specific mouse model was developed. Keratin 14-mediated Cre recombinase expression induced expression of MCPyV T antigens in stratified squamous epithelial cells and Merkel cells of the skin epidermis. Mice expressing MCPyV T antigens developed hyperplasia, hyperkeratosis, and acanthosis of the skin with additional abnormalities in whisker pads, footpads, and eyes. Nearly half of the mice also developed cutaneous papillomas. Evidence for neoplastic progression within stratified epithelia included increased cellular proliferation, unscheduled DNA synthesis, increased E2F-responsive genes levels, disrupted differentiation, and presence of a DNA damage response. These results indicate that MCPyV T antigens are tumorigenic in vivo, consistent with their suspected etiologic role in human cancer. C1 [Spurgeon, Megan E.; Lambert, Paul F.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Oncol, McArdle Lab Canc Res, Madison, WI USA. [Cheng, Jingwei; DeCaprio, James A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Cheng, Jingwei; DeCaprio, James A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Cheng, Jingwei; DeCaprio, James A.] Harvard Univ, Sch Med, Boston, MA USA. [Bronson, Roderick T.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM james_decaprio@dfci.harvard.edu FU U.S. Public Health Service [R01 CA63113, R01 CA173023, P01 CA050661, P01 CA022443]; University of Wisconsin Investigative Dermatology Training Program [T32AR055893]; National Institute of Allergy and Infectious Diseases T32 Training Program [AI078985] FX This work was supported in part by U.S. Public Health Service grants R01 CA63113, R01 CA173023, and P01 CA050661 (J.A. DeCaprio) and P01 CA022443 (P.F. Lambert). M.E. Spurgeon was supported by the University of Wisconsin Investigative Dermatology Training Program T32AR055893 and the National Institute of Allergy and Infectious Diseases T32 Training Program AI078985. NR 47 TC 12 Z9 12 U1 1 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2015 VL 75 IS 6 BP 1068 EP 1079 DI 10.1158/0008-5472.CAN-14-2425 PG 12 WC Oncology SC Oncology GA CE6IZ UT WOS:000351941400016 PM 25596282 ER PT J AU Arvold, ND Catalano, PJ AF Arvold, Nils D. Catalano, Paul J. TI Local Therapies for Brain Metastases, Competing Risks, and Overall Survival SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID CELL LUNG-CANCER; STEREOTACTIC RADIOSURGERY; RADIATION-THERAPY; ONCOLOGY-GROUP; PHASE-III; SURGICAL RESECTION; RADIOTHERAPY; TRIAL; FAILURE C1 [Arvold, Nils D.] Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Catalano, Paul J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. [Catalano, Paul J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Arvold, ND (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM narvold@partners.org NR 17 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 2015 VL 91 IS 4 BP 718 EP 720 DI 10.1016/j.ijrobp.2014.12.003 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CE3NN UT WOS:000351733500009 PM 25752383 ER PT J AU Chandra, RA Miller, CL Skolny, MN Warren, LEG Horick, N Jammallo, LS Sadek, BT Shenouda, MN O'Toole, J Specht, MC Taghian, AG AF Chandra, Ravi A. Miller, Cynthia L. Skolny, Melissa N. Warren, Laura E. G. Horick, Nora Jammallo, Lauren S. Sadek, Betro T. Shenouda, Mina N. O'Toole, Jean Specht, Michelle C. Taghian, Alphonse G. TI Radiation Therapy Risk Factors for Development of Lymphedema in Patients Treated With Regional Lymph Node Irradiation for Breast Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID PREMENOPAUSAL WOMEN; RADIOTHERAPY; CHEMOTHERAPY AB Purpose: We previously evaluated the risk of breast cancer-related lymphedema (LE) with the addition of regional lymph node irradiation (RLNR) and found an increased risk when RLNR is used. Here we analyze the association of technical radiation therapy (RT) factors in RLNR patients with the risk of LE development. Methods and Materials: From 2005 to 2012, we prospectively screened 1476 women for LE who underwent surgery for breast cancer. Among 1507 breasts treated, 172 received RLNR and had complete technical data for analysis. RLNR was delivered as supraclavicular (SC) irradiation (69% [118 of 172 patients]) or SC plus posterior axillary boost (PAB) (31% [54 of 172]). Bilateral arm volume measurements were performed pre-and postoperatively. Patients' RT plans were analyzed for SC field lateral border (relative to the humeral head), total dose to SC, RT fraction size, beam energy, and type of tangent (normal vs wide). Cox proportional hazards models were used to analyze associated risk factors for LE. Results: Median postoperative follow-up was 29.3 months (range: 4.9-74.1 months). The 2-year cumulative incidence of LE was 22% (95% confidence interval [CI]: 15%-32%) for SC and 20% (95% CI: 11%-37%) for SC plus PAB (SC+PAB). None of the analyzed variables was significantly associated with LE risk (extent of humeral head: P=.74 for <1/3 vs >2/3, PZ. 41 for 1/3 to 2/3 vs >2/3; P=.40 for fraction size of 1.8 Gy vs 2.0 Gy; P=. 57 for beam energy 6 MV vs 10 MV; P=. 74 for tangent type wide vs regular; P=. 66 for SC vs SC+PAB). Only pretreatment body mass index (hazard ratio [HR]: 1.09; 95% CI: 1.04-1.15, P=. 0007) and the use of axillary lymph node dissection (HR: 7.08, 95% CI: 0.98-51.40, P=. 05) were associated with risk of subsequent LE development. Conclusions: Of the RT parameters tested, none was associated with an increased risk of LE development. This study underscores the need for future work investigating alternative RLNR risk factors for LE. (C) 2015 Elsevier Inc. All rights reserved. C1 [Chandra, Ravi A.; Warren, Laura E. G.] Harvard Radiat Oncol Program, Boston, MA USA. [Miller, Cynthia L.] Harvard Univ, Sch Med, Boston, MA USA. [Skolny, Melissa N.; Jammallo, Lauren S.; Sadek, Betro T.; Shenouda, Mina N.; Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Horick, Nora] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [O'Toole, Jean] Massachusetts Gen Hosp, Dept Phys & Occupat Therapy, Boston, MA 02114 USA. [Specht, Michelle C.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. RP Taghian, AG (reprint author), 100 Blossom St, Boston, MA 02114 USA. EM ataghian@partners.org RI Sadek, Betro/I-7734-2013 OI Sadek, Betro/0000-0003-0119-7207 FU National Cancer Institute [R01CA139118, P50CA089393]; Adele McKinnon Research Fund for Breast Cancer-Related Lymphedema FX The study described was supported by Award Number R01CA139118 (AGT), Award Number P50CA089393 (AGT) from the National Cancer Institute and the Adele McKinnon Research Fund for Breast Cancer-Related Lymphedema. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 14 TC 9 Z9 9 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 2015 VL 91 IS 4 BP 760 EP 764 DI 10.1016/j.ijrobp.2014.12.029 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CE3NN UT WOS:000351733500015 PM 25752389 ER PT J AU Chen, AB AF Chen, Aileen B. TI Fate of Manuscripts Rejected From the Red Journal In Reply SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Letter ID DEFINITIVE PRIMARY THERAPY; CELL LUNG-CANCER C1 Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Chen, AB (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. OI Chen, Aileen/0000-0002-5385-3360 NR 2 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 2015 VL 91 IS 4 BP 880 EP 881 DI 10.1016/j.ijrobp.2014.12.015 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CE3NN UT WOS:000351733500034 PM 25752408 ER PT J AU De Luca, G van't Hof, AWJ Gibson, CM Cutlip, D Zeymer, U Noc, M Maioli, M Zorman, S Gabriel, HM Emre, A Rakowski, T Gyongyosi, M Huber, K Bellandi, F Dudek, D AF De Luca, Giuseppe van't Hof, Arnoud W. J. Gibson, C. Michael Cutlip, Donald Zeymer, Uwe Noc, Marko Maioli, Mauro Zorman, Simona Gabriel, H. Mesquita Emre, Ayse Rakowski, Tomasz Gyongyosi, Maryann Huber, Kurt Bellandi, Francesco Dudek, Dariusz CA EGYPT Cooperation TI Impact of Time from Symptom Onset to Drug Administration on Outcome in Patients Undergoing Glycoprotein IIb-IIIa Facilitated Primary Angioplasty (from the EGYPT Cooperation) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ELEVATION MYOCARDIAL-INFARCTION; PERCUTANEOUS CORONARY INTERVENTION; RANDOMIZED-TRIALS; DATA METAANALYSIS; STEMI PATIENTS; TO-TREATMENT; REPERFUSION; SIZE; INHIBITORS; MORTALITY AB Contrasting data have been so far reported on facilitation with glycoprotein Jib-IIIa inhibitors (GpIIbIIIa) in patients who underwent primary percutaneous coronary intervention. However, it has been demonstrated a time-dependent composition of coronary thrombus in ST-segment elevation myocardial infarction, with more platelets in the first hours. Subsequently, the benefits of early administration of GpIIbIIIa may be affected by the time from symptoms onset to GpIIbIIIa, that therefore is the am of this study. Our population is represented by 814 patients who underwent GpIIbIIIa facilitated primary angioplasty included in the Early glycoprotein lib-IIIa inhibitors in primary angioplasty database. Patients were divided according to quartiles of time from symptom onset to GpIIbIIIa administration (565 minutes; 65 to 100 minutes; 101 to 178 minutes; and >178 minutes). Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Time from symptoms onset to GpIIbIIIa was linearly associated with hypertension, diabetes, hypercholesterolemia, and previous myocardial infarction but inversely associated with smoking. Abciximab was more often administrated later from symptoms onset. Time from symptoms onset to GpIIbIIIa was significantly associated with the rate of preprocedural recanalization (thrombolysis in myocardial infarction [TIMI] 2 to 3; p <0.001), postprocedural TIM! 3 flow (p <0.001), the rate of complete ST-segment resolution (p <0.001), and the rate of myocardial blush grade 2 to 3 (p <0.001) and inversely associated with the occurrence of distal embolization (p <0.001). Follow-up data were collected at a median (twenty-fifth to seventy-fifth) of 360 (30 to 1,095) days. A total of 52 patients had died. Time to GpIIbIIIa had a significant impact on mortality (hazard ratio [95% confidence interval] 1.46 [1.11 to 1.92], p = 0.007) that was confirmed after correction for baseline confounding factors (adjusted hazard ratio [95% confidence interval] 1.41 [1.02 to 2.21], p = 0.042). In conclusion, this study showed that in patients who underwent primary angioplasty with upstream GpIIbIIIa, time from symptoms onset to GpIIbIIIa strongly impacts on preprocedural recanalization, distal embolization, myocardial perfusion, and long-term survival. (C) 2015 Elsevier Inc. All rights reserved. C1 [De Luca, Giuseppe] Eastern Piedmont Univ, Maggiore della Carita Hosp, Div Cardiol, Novara, Italy. [van't Hof, Arnoud W. J.] Hosp Weezenlanden, Div Cardiol, Zwolle, Netherlands. [Gibson, C. Michael] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Cutlip, Donald] Beth Israel Deaconess Med Ctr, Intervent Cardiol Sect, Boston, MA 02215 USA. [Zeymer, Uwe] Herzzentrum Ludwigshafen, Div Cardiol, Ludwigshafen, Germany. [Noc, Marko; Zorman, Simona] Univ Med Ctr, Ctr Intens Internal Med, Ljubljana, Slovenia. [Maioli, Mauro; Bellandi, Francesco] Prato Hosp, Prato, Italy. [Gabriel, H. Mesquita] Hosp Santa Maria, Div Cardiol, Lisbon, Portugal. [Emre, Ayse] Siyami Ersek Thorac & Cardiovasc Surg Ctr, Istanbul, Turkey. [Rakowski, Tomasz; Dudek, Dariusz] Jagiellonian Univ, Inst Cardiol, Dept Cardiol 2, Krakow, Poland. [Gyongyosi, Maryann] Med Univ Vienna, Dept Cardiol, Vienna, Austria. [Huber, Kurt] Wilhelminenspital Stadt Wien, Dept Med Cardiol & Emergency Med 3, Vienna, Austria. RP De Luca, G (reprint author), Eastern Piedmont Univ, Maggiore della Carita Hosp, Div Cardiol, Novara, Italy. EM giuseppe.deluca@maggioreosp.novara.it NR 30 TC 4 Z9 4 U1 2 U2 4 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 MAR 15 PY 2015 VL 115 IS 6 BP 711 EP 715 DI 10.1016/j.amjcard.2014.12.030 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE0GO UT WOS:000351482700002 PM 25655867 ER PT J AU Gao, L Park, SJ Jang, Y Lee, S Tian, JW Minami, Y Jia, HB Ong, D Soeda, T Vergallo, R Lee, H Yu, B Uemura, S Jang, IK AF Gao, Lei Park, Seung-Jung Jang, Yangsoo Lee, Stephen Tian, Jinwei Minami, Yoshiyasu Jia, Haibo Ong, Daniel Soeda, Tsunenari Vergallo, Rocco Lee, Hang Yu, Bo Uemura, Shiro Jang, Ik-Kyung TI Optical Coherence Tomographic Evaluation of the Effect of Cigarette Smoking on Vascular Healing After Sirolimus-Eluting Stent Implantation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ENDOTHELIAL PROGENITOR CELLS; ANGIOGENESIS; THROMBOSIS AB Cigarette smoking is known to be deleterious to patients with coronary artery disease; however, the effect of smoking on vascular responses after coronary drug-eluting stent implantation is unknown. We sought to examine vascular response after sirolimus-eluting stent implantation in patients with ongoing smoking using optical coherence tomography, compared with former smokers and nonsmokers. We identified 181 sirolimus-eluting stents in 140 subjects who underwent follow-up optical coherence tomography imaging. Subjects were divided into 3 groups: current smokers (n = 28), former smokers (n = 35), and nonsmokers (n = 77). Stent strut coverage, neointimal characteristics, and strut malapposition were evaluated. The incidence of uncovered stent struts was significantly higher in nonsmokers compared with current smokers (13.3 +/- 13.3% vs 6.7 +/- 8.3%; p = 0.001). On qualitative evaluation of neointimal morphology, the prevalence of heterogeneous neointima was higher in current smokers (71.9%) than in former smokers (36.0%) or nonsmokers (10.1%) (p = 0.004 and p <0.001, respectively). There was no difference in the incidence of malapposition among the 3 groups. Multivariate modeling showed that current smoking was negatively associated with the presence of uncovered struts (odds ratio 0.33; 95% confidence interval 0.14 to 0.79; p = 0.013) and positively associated with the presence of heterogeneous neointima (odds ratio 9.47; 95% confidence interval 3.79 to 23.72; p <0.001). In conclusion, the incidence of strut coverage was higher in current smokers compared with nonsmokers. However, the pattern of neointima was more heterogeneous in current smokers. (C) 2015 Elsevier Inc. All rights reserved. C1 [Gao, Lei; Tian, Jinwei; Minami, Yoshiyasu; Jia, Haibo; Ong, Daniel; Soeda, Tsunenari; Vergallo, Rocco; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02138 USA. [Lee, Hang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA. [Park, Seung-Jung] Univ Ulsan, Coll Med, Asan Med Ctr, Div Cardiol, Seoul, South Korea. [Jang, Yangsoo] Yonsei Univ, Coll Med, Severance Cardiovasc Hosp, Div Cardiol, Seoul, South Korea. [Lee, Stephen] Univ Hong Kong, Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China. [Tian, Jinwei; Jia, Haibo; Yu, Bo] Harbin Med Univ, Chinese Minist Educ, Key Lab Myocardial Ischemia, Dept Cardiol,Affiliated Hosp 2, Harbin, Peoples R China. [Soeda, Tsunenari; Uemura, Shiro] Nara Med Univ, Dept Med 1, Nara, Japan. [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 02138 USA. EM ijang@mgh.harvard.edu FU St. Jude Medical, Westford, MA, USA; Boston Scientific Corp., Marlborough, MA, USA; Dr. John Nam OCT fellowship grant; Michael A. Park grant; National Natural Science Foundation of China, Beijing, P.R.China [81300201, 81200076, 30871064]; China Postdoctoral Science Foundation, Beijing, P.R.China [2013M531074]; Heilongjiang Postdoctoral Science Foundation, Haerbin, Heilongjiang, P.R.China [LBH-Z12180]; Italian Society of Cardiology Award FX Dr. Jang reports receiving a research grant and honorarium from St. Jude Medical, Westford, MA, USA and research grant from Boston Scientific Corp., Marlborough, MA, USA. This study was supported by the Dr. John Nam OCT fellowship grant and "Michael A. Park grant." Dr. Tian has received a grant from the National Natural Science Foundation of China, Beijing, P.R.China (81300201), a grant from China Postdoctoral Science Foundation, Beijing, P.R.China (2013M531074), and a grant from Heilongjiang Postdoctoral Science Foundation, Haerbin, Heilongjiang, P.R.China (LBH-Z12180). Dr. Jia received a grant from the National Natural Science Foundation of China, Beijing, P.R.China (81200076). Dr. Vergallo was funded in part by the 2013 Italian Society of Cardiology Award for Research Abroad. Dr. Yu received a grant from the National Natural Science Foundation of China, Beijing, P.R.China (30871064). NR 21 TC 1 Z9 1 U1 0 U2 0 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 MAR 15 PY 2015 VL 115 IS 6 BP 751 EP 757 DI 10.1016/j.amjcard.2014.12.038 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE0GO UT WOS:000351482700008 PM 25620038 ER PT J AU Khan, SS Campia, U Chioncel, O Zannad, F Rossignol, P Maggioni, AP Swedberg, K Konstam, MA Senni, M Nodari, S Vaduganathan, M Subacius, H Butler, J Gheorghiade, M AF Khan, Sadiya S. Campia, Umberto Chioncel, Ovidiu Zannad, Faiez Rossignol, Patrick Maggioni, Aldo P. Swedberg, Karl Konstam, Marvin A. Senni, Michele Nodari, Savina Vaduganathan, Muthiah Subacius, Haris Butler, Javed Gheorghiade, Mihai CA EVEREST Trial Investigators TI Changes in Serum Potassium Levels During Hospitalization in Patients With Worsening Heart Failure and Reduced Ejection Fraction (from the EVEREST Trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; RENAL-FUNCTION; DOUBLE-BLIND; HYPERKALEMIA; TOLVAPTAN; MORTALITY; PLACEBO; MILD; ANTAGONIST; RATIONALE AB Both hyperkalemia and hypokalemia may be related to heart failure (HF) therapy and are associated with adverse outcomes. Abnormalities in serum potassium levels in hospitalized patients with HF and reduced ejection fraction (EF) have not been previously investigated. A post hoc analysis was performed in 1,907 hospitalized patients with worsening HF and reduced EF in the placebo arm of the Efficacy of Vasopressin Antagonism in HF Outcome Study with Tolvaptan (EVEREST) trial. Serum potassium was measured at randomization and at discharge or day 7. The co-primary end points were all-cause mortality (ACM) and cardiovascular mortality or the first HF hospitalization (CVM + HFH). The association between inhospital change in potassium levels and time to outcomes was evaluated using multivariate Cox regression models. Study participants had a mean age of 65.6 +/- 12.0 years and were on optimal guideline-directed medical therapies, including beta blockers (77%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (85%), and aldosterone antagonists (55%). Baseline potassium concentration was 4.3 +/- 0.6 mEq/l, and hyperkalemia or hypokalemia was seen in 6.5% of the participants. On average, serum potassium level increased by 0.21 +/- 0.66 mEq/l, p < 0.0001, during hospitalization. Inhospital potassium change was not associated with either the primary or the secondary end point over a median follow-up of 9.9 months. In conclusion, in patients with reduced EF hospitalized for worsening HF, serum potassium abnormalities are common at baseline (within 48 hours of admission) and potassium levels increase during hospitalization, despite aggressive diuretic therapy. However, they are not associated with all-cause or CVM or HFH. Inhospital changes in potassium may limit the implementation of evidence-based therapies such as mineralocorticoid receptor antagonists. (C) 2015 Elsevier Inc. All rights reserved. C1 [Khan, Sadiya S.; Subacius, Haris] Northwestern Univ, Dept Med, Div Cardiol, Feinberg Sch Med, Chicago, IL 60611 USA. [Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Campia, Umberto] MedStar Heart Inst, Washington, DC USA. [Campia, Umberto] MedStar Cardiovasc Res Network, Washington, DC USA. [Chioncel, Ovidiu] Inst Boli Cardiovasc CC Iliescu, Cardiol 1, Bucharest, Romania. [Zannad, Faiez; Rossignol, Patrick] Univ Lorraine, INSERM, Ctr Invest Clin, Nancy, France. [Zannad, Faiez; Rossignol, Patrick] CHU Nancy, Nancy, France. [Maggioni, Aldo P.] ANMCO Res Ctr, Florence, Italy. [Swedberg, Karl] Univ Gothenburg, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden. [Konstam, Marvin A.] Tufts Med Ctr, Ctr Cardiovasc, Boston, MA USA. [Senni, Michele] Osped Papa Giovanni XXIII, Cardiovasc Dept, Bergamo, Italy. [Nodari, Savina] Univ Brescia, Dept Cardiol, Brescia, Italy. [Vaduganathan, Muthiah] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Butler, Javed] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu OI chioncel, ovidiu/0000-0002-3197-3628; Maggioni, Aldo Pietro/0000-0003-2764-6779 FU Otsuka Inc. (Rockville, Maryland) FX Otsuka Inc. (Rockville, Maryland) provided financial and material support for the EVEREST trial. Database management was performed by the sponsor. NR 21 TC 8 Z9 9 U1 0 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 15 PY 2015 VL 115 IS 6 BP 790 EP 796 DI 10.1016/j.amjcard.2014.12.045 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE0GO UT WOS:000351482700014 PM 25728846 ER PT J AU Yancey, DM Guichard, JL Ahmed, MI Zhou, LF Murphy, MP Johnson, MS Benavides, GA Collawn, J Darley-Usmar, V Dell'Italia, LJ AF Yancey, Danielle M. Guichard, Jason L. Ahmed, Mustafa I. Zhou, Lufang Murphy, Michael P. Johnson, Michelle S. Benavides, Gloria A. Collawn, James Darley-Usmar, Victor Dell'Italia, Louis J. TI Cardiomyocyte mitochondrial oxidative stress and cytoskeletal breakdown in the heart with a primary volume overload SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE heart failure; mitochondria; cardiomyocyte ID ISOLATED MITRAL REGURGITATION; MICE LACKING DESMIN; HYPERTROPHIED MYOCARDIUM; CONTRACTILE DYSFUNCTION; EXTRACELLULAR-MATRIX; CARDIAC DYSFUNCTION; SKELETAL MYOPATHY; XANTHINE-OXIDASE; FAILURE; BIOENERGETICS AB Left ventricular (LV) volume overload (VO) results in cardiomyocyte oxidative stress and mitochondrial dysfunction. Because mitochondria are both a source and target of ROS, we hypothesized that the mitochondrially targeted antioxidant mitoubiquinone (MitoQ) will improve cardiomyocyte damage and LV dysfunction in VO. Isolated cardiomyocytes from Sprague-Dawley rats were exposed to stretch in vitro and VO of aortocaval fistula (ACF) in vivo. ACF rats were treated with and without MitoQ. Isolated cardiomyocytes were analyzed after 3 h of cyclical stretch or 8 wk of ACF with MitoSox red or 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate to measure ROS and with tetramethylrhodamine to measure mitochondrial membrane potential. Transmission electron microscopy and immunohistochemistry were used for cardiomyocyte structural assessment. In vitro cyclical stretch and 8-wk ACF resulted in increased cardiomyocyte mitochondrial ROS production and decreased mitochondrial membrane potential, which were significantly improved by MitoQ. ACF had extensive loss of desmin and beta(2)-tubulin that was paralleled by mitochondrial disorganization, loss of cristae, swelling, and clustering identified by mitochondria complex IV staining and transmission electron microscopy. MitoQ improved mitochondrial structural damage and attenuated desmin loss/degradation evidenced by immunohistochemistry and protein expression. However, LV dilatation and fractional shortening were unaffected by MitoQ treatment in 8-wk ACF. In conclusion, although MitoQ did not affect LV dilatation or function in ACF, these experiments suggest a connection of cardiomyocyte mitochondria-derived ROS production with cytoskeletal disruption and mitochondrial damage in the VO of ACF. C1 [Dell'Italia, Louis J.] Dept Vet Affairs Med Ctr, Birmingham, AL USA. [Yancey, Danielle M.; Guichard, Jason L.; Ahmed, Mustafa I.; Zhou, Lufang; Dell'Italia, Louis J.] Univ Alabama Birmingham, UAB Comprehens Cardiovasc Ctr, Birmingham, AL USA. [Yancey, Danielle M.; Guichard, Jason L.; Ahmed, Mustafa I.; Zhou, Lufang; Dell'Italia, Louis J.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Johnson, Michelle S.; Benavides, Gloria A.; Darley-Usmar, Victor] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Johnson, Michelle S.; Benavides, Gloria A.; Darley-Usmar, Victor] Univ Alabama Birmingham, UAB Ctr Free Radical Biol, Birmingham, AL USA. [Murphy, Michael P.] MRC, Mitochondrial Biol Unit, Cambridge, England. [Collawn, James] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL USA. RP Dell'Italia, LJ (reprint author), Birmingham Vet Affairs Med Ctr, 700 S 19th St, Birmingham, AL 35294 USA. EM louis.dellitalia@va.gov FU American Heart Association Predoctoral Fellowship [13PRE14560035]; National Heart, Lung, and Blood Institute Training Grant [5-T32-HL-072757, R01-HL-54816] FX This work was supported by American Heart Association Predoctoral Fellowship 13PRE14560035 (to D. M. Yancey) and National Heart, Lung, and Blood Institute Training Grant 5-T32-HL-072757 (to J. L. Guichard) and Grant R01-HL-54816 (to L. J. Dell'Italia). NR 47 TC 12 Z9 12 U1 0 U2 12 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAR 15 PY 2015 VL 308 IS 6 BP H651 EP H663 DI 10.1152/ajpheart.00638.2014 PG 13 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA CD3OU UT WOS:000350988900009 PM 25599572 ER PT J AU Branson, RD Hess, DR AF Branson, Richard D. Hess, Dean R. TI Lost in Translation: Failure of Tracheal Tube Modifications to Impact Ventilator-associated Pneumonia SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID ENDOTRACHEAL-TUBE C1 [Branson, Richard D.] Univ Cincinnati, Cincinnati, OH 45220 USA. [Hess, Dean R.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Hess, Dean R.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. RP Branson, RD (reprint author), Univ Cincinnati, Cincinnati, OH 45220 USA. NR 16 TC 4 Z9 4 U1 0 U2 1 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 MAR 15 PY 2015 VL 191 IS 6 BP 606 EP 608 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CD7FW UT WOS:000351257200002 PM 25767919 ER PT J AU Mylonakis, E Clancy, CJ Ostrosky-Zeichner, L Garey, KW Alangaden, GJ Vazquez, JA Groeger, JS Judson, MA Vinagre, YM Heard, SO Zervou, FN Zacharioudakis, IM Kontoyiannis, DP Pappas, PG AF Mylonakis, Eleftherios Clancy, Cornelius J. Ostrosky-Zeichner, Luis Garey, Kevin W. Alangaden, George J. Vazquez, Jose A. Groeger, Jeffrey S. Judson, Marc A. Vinagre, Yuka-Marie Heard, Stephen O. Zervou, Fainareti N. Zacharioudakis, Ioannis M. Kontoyiannis, Dimitrios P. Pappas, Peter G. TI T2 Magnetic Resonance Assay for the Rapid Diagnosis of Candidemia in Whole Blood: A Clinical Trial SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE T2 magnetic resonance; T2MR; Candida; fungal infections; clinical trial ID INVASIVE CANDIDIASIS; ECHINOCANDIN RESISTANCE; OPPORTUNISTIC YEAST; ANTIFUNGAL THERAPY; FUNGAL-INFECTIONS; RISK-FACTORS; CULTURE; MANAGEMENT; TIME; FLUCONAZOLE AB Background. Microbiologic cultures, the current gold standard diagnostic method for invasive Candida infections, have low specificity and take up to 2-5 days to grow. We present the results of the first extensive multicenter clinical trial of a new nanodiagnostic approach, T2 magnetic resonance (T2MR), for diagnosis of candidemia. Methods. Blood specimens were collected from 1801 hospitalized patients who had a blood culture ordered for routine standard of care; 250 of them were manually supplemented with concentrations from <1 to 100 colonyforming units (CFUs)/mL for 5 different Candida species. Results. T2MR demonstrated an overall specificity per assay of 99.4% (95% confidence interval [CI], 99.1%-99.6%) with a mean time to negative result of 4.2 +/- 0.9 hours. Subanalysis yielded a specificity of 98.9% (95% CI, 98.3%-99.4%) for Candida albicans/Candida tropicalis, 99.3% (95% CI, 98.7%-99.6%) for Candida parapsilosis, and 99.9% (95% CI, 99.7%-100.0%) for Candida krusei/Candida glabrata. The overall sensitivity was found to be 91.1% (95% CI, 86.9%-94.2%) with a mean time of 4.4 +/- 1.0 hours for detection and species identification. The subgroup analysis showed a sensitivity of 92.3% (95% CI, 85.4%-96.6%) for C. albicans/C. tropicalis, 94.2% (95% CI, 84.1%-98.8%) for C. parapsilosis, and 88.1% (95% CI, 80.2%-93.7%) for C. krusei/C. glabrata. The limit of detection was 1 CFU/mL for C. tropicalis and C. krusei, 2 CFU/mL for C. albicans and C. glabrata, and 3 CFU/mL for C. parapsilosis. The negative predictive value was estimated to range from 99.5% to 99.0% in a study population with 5% and 10% prevalence of candidemia, respectively. Conclusions. T2MR is the first fully automated technology that directly analyzes whole blood specimens to identify species without the need for prior isolation of Candida species, and represents a breakthrough shift into a new era of molecular diagnostics. C1 [Mylonakis, Eleftherios; Zervou, Fainareti N.; Zacharioudakis, Ioannis M.] Brown Univ, Rhode Isl Hosp, Div Infect Dis, Warren Alpert Med Sch, Providence, RI 02903 USA. [Clancy, Cornelius J.] Univ Pittsburgh, Vet Affairs Pittsburgh Healthcare Syst, Div Infect Dis, Pittsburgh, PA 15260 USA. [Ostrosky-Zeichner, Luis] Univ Texas Med Sch Houston, Div Infect Dis, Houston, TX USA. [Ostrosky-Zeichner, Luis] Mem Hermann Texas Med Ctr, Houston, TX USA. [Garey, Kevin W.] Univ Houston, Coll Pharm, Houston, TX 77004 USA. [Alangaden, George J.] Henry Ford Hlth Syst, Div Infect Dis, Detroit, MI USA. [Vazquez, Jose A.] Georgia Regents Univ, Med Coll Georgia, Dept Med, Augusta, GA USA. [Groeger, Jeffrey S.] Mem Sloan Kettering Canc Ctr, Urgent Care Serv, New York, NY 10021 USA. [Judson, Marc A.] Albany Med Coll, Div Pulm & Crit Care Med, New York, NY USA. [Vinagre, Yuka-Marie] St Vincent Hosp, Dept Crit Care Med, Worcester, MA 01604 USA. [Heard, Stephen O.] UMass Mem Med Ctr, Dept Anesthesiol, Worcester, MA USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Dept Infect Dis Infect Control & Employee Hlth, Houston, TX 77030 USA. [Pappas, Peter G.] Univ Alabama, Div Infect Dis, Birmingham, W Midlands, England. RP Mylonakis, E (reprint author), Brown Univ, Rhode Isl Hosp, Div Infect Dis, Warren Alpert Med Sch, 593 Eddy St,3rd Floor,Ste 328-330, Providence, RI 02903 USA. EM emylonakis@lifespan.org OI Garey, Kevin/0000-0003-2063-7503 FU T2 Biosystems FX This work was supported by T2 Biosystems. NR 39 TC 60 Z9 60 U1 2 U2 13 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 15 PY 2015 VL 60 IS 6 BP 892 EP 899 DI 10.1093/cid/ciu959 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CD4KP UT WOS:000351051600012 PM 25586686 ER PT J AU Walensky, RP Auerbach, JD AF Walensky, Rochelle P. Auerbach, Judith D. CA Off AIDS Res Advisory Council TI Focusing National Institutes of Health HIV/AIDS Research for Maximum Population Impact SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material DE HIV; AIDS; research; National Institutes of Health (NIH) ID HIV; CARE; PREVENTION; INFECTION AB Progress in advancing research on the pathophysiology, prevention, treatment, and impact of human immunodeficiency virus (HIV) is threatened by the decaying purchasing power of National Institutes of Health (NIH) dollars. A working group of the NIH Office of AIDS Research Advisory Council was charged by the NIH Director with developing a focused and concise blueprint to guide the use of limited funding over the next few years. Science priorities outlined by the working group and reported here are intended to maximally address individuals, groups, and settings most affected by the epidemic, and to redress shortcomings in realizing population-level HIV prevention, treatment, and eradication goals. Optimizing these priorities requires that traditional silos-defined by topic focus and by scientific discipline-be dissolved and that structural issues affecting the pipeline of new investigators and the ability of the Office of AIDS Research to fulfill its role of steward of the NIH HIV/AIDS research program be directly addressed. C1 [Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Dept Med, Boston, MA 02114 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Walensky, Rochelle P.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Auerbach, Judith D.] Univ Calif San Francisco, Sch Med, Div Med, Ctr AIDS Prevent Studies, San Francisco, CA USA. RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Div Infect Dis, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM rwalensky@partners.org FU NIMH NIH HHS [P30 MH062246] NR 15 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 15 PY 2015 VL 60 IS 6 BP 937 EP 940 DI 10.1093/cid/ciu942 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CD4KP UT WOS:000351051600020 PM 25422391 ER PT J AU Pandit, MM Inscho, EW Zhang, SL Seki, T Rohatgi, R Gusella, L Kishore, B Kohan, DE AF Pandit, Meghana M. Inscho, Edward W. Zhang, Shali Seki, Tsugio Rohatgi, Rajeev Gusella, Luca Kishore, Bellamkonda Kohan, Donald E. TI Flow regulation of endothelin-1 production in the inner medullary collecting duct SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE collecting duct; endothelin; flow; purinergic ID POLYCYSTIC KIDNEY-DISEASE; EPITHELIAL NA+ CHANNEL; ESSENTIAL-HYPERTENSION; URINARY ENDOTHELIN-1; SODIUM RETENTION; PRINCIPAL CELLS; TRPC3 CHANNELS; BLOOD-PRESSURE; PRIMARY CILIUM; SHEAR-STRESS AB Collecting duct-derived endothelin (ET)-1 is an autocrine inhibitor of Na+ and water reabsorption; its deficiency causes hypertension and water retention. Extracellular fluid volume expansion increases collecting duct ET-1, thereby promoting natriuresis and diuresis; however, how this coupling between volume expansion and collecting duct ET-1 occurs is incompletely understood. One possibility is that volume expansion increases tubular fluid flow. To investigate this, cultured IMCD3 cells were subjected to static or flow conditions. Exposure to a shear stress of 2 dyn/cm(2) for 2 h increased ET-1 mRNA content by similar to 2.3-fold. Absence of perfusate Ca2+, chelation of intracellular Ca2+, or inhibition of Ca2+ signaling (calmodulin, Ca2+/calmodulin-dependent kinase, calcineurin, PKC, or phospholipase C) prevented the flow response. Evaluation of possible flow-activated Ca2+ entry pathways revealed no role for transient receptor potential (TRP)C3, TRPC6, and TRPV4; however, cells with TRPP2 (polycystin-2) knockdown had no ET-1 flow response. Flow increased intracellular Ca2+ was blunted in TRPP2 knockdown cells. Nonspecific blockade of P2 receptors, as well as specific inhibition of P2X(7) and P2Y(2) receptors, prevented the ET-1 flow response. The ET-1 flow response was not affected by inhibition of either epithelial Na+ channels or the mitochondrial Na+/Ca2+ exchanger. Taken together, these findings provide evidence that in IMCD3 cells, flow, via polycystin-2 and P2 receptors, engages Ca2+ dependent signaling pathways that stimulate ET-1 synthesis. C1 [Pandit, Meghana M.; Kishore, Bellamkonda; Kohan, Donald E.] Univ Utah, Hlth Sci Ctr, Div Nephrol, Salt Lake City, UT 84132 USA. [Pandit, Meghana M.; Kohan, Donald E.] Dept Pharmaceut & Pharmaceut Chem, Salt Lake City, UT USA. [Inscho, Edward W.; Zhang, Shali] Univ Alabama Birmingham, Birmingham, AL USA. [Seki, Tsugio] Calif Northstate Univ, Dept Med Educ, Elk Grove, CA USA. [Rohatgi, Rajeev; Gusella, Luca] James J Peter Vet Affairs Med Ctr, Dept Med, Bronx, NY USA. [Rohatgi, Rajeev; Gusella, Luca] Icahn Sch Med Mt Sinai, Dept Med & Pediat, New York, NY 10029 USA. [Kishore, Bellamkonda; Kohan, Donald E.] Salt Lake Vet Affairs Med Ctr, Salt Lake City, UT USA. RP Kohan, DE (reprint author), Univ Utah, Hlth Sci Ctr, Div Nephrol, 1900 E 30 N, Salt Lake City, UT 84132 USA. EM donald.kohan@hsc.utah.edu OI Kishore, Bellamkonda/0000-0001-8232-9827 FU National Institutes of Health (NIH) [P01-HL-095499]; Veterans Affairs Merit Reviews; NIH [DK-044628, HL-098135] FX This work was supported in part by National Institutes of Health (NIH) Grants P01-HL-095499 (to D. E. Kohan and E. W. Inscho), Veterans Affairs Merit Reviews (to R. Rohatgi and to B. Kishore), and NIH Grants DK-044628 and HL-098135 (to E. W. Inscho). NR 57 TC 7 Z9 7 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAR 15 PY 2015 VL 308 IS 6 BP F541 EP F552 DI 10.1152/ajprenal.00456.2014 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA CD4NT UT WOS:000351060800004 PM 25587122 ER PT J AU Oreskovic, NM Perrin, JM Robinson, AI Locascio, JJ Blossom, J Chen, ML Winickoff, JP Field, AE Green, C Goodman, E AF Oreskovic, Nicolas M. Perrin, James M. Robinson, Alyssa I. Locascio, Joseph J. Blossom, Jeff Chen, Minghua L. Winickoff, Jonathan P. Field, Alison E. Green, Chloe Goodman, Elizabeth TI Adolescents' use of the built environment for physical activity SO BMC PUBLIC HEALTH LA English DT Article DE Physical activity; Built environment; Accelerometer; Adolescents; Global positioning system; Geographic information systems ID AMERICAN-HEART-ASSOCIATION; ACCELEROMETER DATA; SPORTS-MEDICINE; PUBLIC-HEALTH; PEACH PROJECT; CHILDREN; OBESITY; GPS; RECOMMENDATION; OVERWEIGHT AB Background: Physical activity is a health-enhancing behavior, but few adolescents achieve the recommended levels of moderate-to-vigorous physical activity. Understanding how adolescents use different built environment spaces for physical activity and activity varies by location could help in designing effective interventions to promote moderate-to-vigorous physical activity. The objective of this study was to describe the locations where adolescents engage in physical activity and compare traditional intensity-based measures with continuous activity when describing built environment use patterns among adolescents. Methods: Eighty adolescents aged 11-14 years recruited from community health and recreation centers. Adolescents wore accelerometers (Actigraph GT3X) and global positioning system receivers (QStarz BT-Q1000XT) for two separate weeks to record their physical activity levels and locations. Accelerometer data provided a continuous measure of physical activity and intensity-based measures (sedentary time, moderate-to-vigorous physical activity). Physical activity was mapped by land-use classification (home, school, park, playground, streets & sidewalks, other) using geographic information systems and this location-based activity was assessed for both continuous and intensity-based physical activity derived from mixed-effects models which accounted for repeated measures and clustering effects within person, date, school, and town. Results: Mean daily moderate-to-vigorous physical activity was 22 minutes, mean sedentary time was 134 minutes. Moderate-to-vigorous physical activity occurred in bouts lasting up to 15 minutes. Compared to being at home, being at school, on the streets and sidewalks, in parks, and playgrounds were all associated with greater odds of being in moderate-to-vigorous physical activity and achieving higher overall activity levels. Playground use was associated with the highest physical activity level (beta = 172 activity counts per minute, SE = 4, p < 0.0001) and greatest odds of being in moderate-to-vigorous physical activity (odds ratio 8.3, 95% confidence interval 4.8-14.2). Conclusion: Adolescents were more likely to engage in physical activity, and achieved their highest physical activity levels, when using built environments located outdoors. Novel objective methods for determining physical activity can provide insight into adolescents' spatial physical activity patterns, which could help guide physical activity interventions. Promoting zoning and health policies that encourage the design and regular use of outdoor spaces may offer another promising opportunity for increasing adolescent physical activity. C1 [Oreskovic, Nicolas M.; Perrin, James M.; Robinson, Alyssa I.; Locascio, Joseph J.; Chen, Minghua L.; Winickoff, Jonathan P.; Goodman, Elizabeth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Oreskovic, Nicolas M.; Perrin, James M.; Locascio, Joseph J.; Chen, Minghua L.; Winickoff, Jonathan P.; Field, Alison E.; Goodman, Elizabeth] Harvard Univ, Sch Med, Boston, MA USA. [Blossom, Jeff; Green, Chloe] Harvard Ctr Geog Anal, Boston, MA USA. [Field, Alison E.] Boston Childrens Hosp, Boston, MA USA. RP Oreskovic, NM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM noreskovic@mgh.harvard.edu FU National Institutes of Health [K23HL103841, P30DK46200] FX The authors gratefully thank Daniel A. Rodriguez, PhD, of University of North Carolina at Chapel Hill for his helpful input on study design and insightful comments on the manuscript. Dr. Oreskovic had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. This study was funded by National Institutes of Health grants K23HL103841 and P30DK46200. NR 27 TC 10 Z9 10 U1 6 U2 32 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD MAR 15 PY 2015 VL 15 AR 251 DI 10.1186/s12889-015-1596-6 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CD7JK UT WOS:000351266400001 PM 25880654 ER PT J AU Hamstra, DA Bae, K Hanks, G Hu, C Shipley, WU Pan, CC Roach, M Lawton, CA Sandler, HM AF Hamstra, Daniel A. Bae, Kyounghwa Hanks, Gerald Hu, Chen Shipley, William U. Pan, Charlie C. Roach, Mack, III Lawton, Colleen A. Sandler, Howard M. TI Impact of Biochemical Failure Classification on Clinical Outcome: A Secondary Analysis of Radiation Therapy Oncology Group 9202 and 9413 SO CANCER LA English DT Article; Proceedings Paper CT 1st Palliative Care in Oncology Symposium CY OCT, 2014 CL Boston, MA DE prostate-specific antigen; prostate-specific antigen failure; radiotherapy ID PROSTATE-SPECIFIC ANTIGEN; ADJUVANT ANDROGEN DEPRIVATION; EXTERNAL-BEAM RADIOTHERAPY; CANCER-SPECIFIC MORTALITY; PHASE-III TRIAL; DOUBLING TIME; COMPETING RISK; MEN; SURVIVAL; INTERVAL AB BACKGROUNDBiochemical failure (BF) after radiation therapy is defined on the basis of a rising prostate-specific antigen (PSA) level (A1 failure) or any event that prompts the initiation of salvage androgen-deprivation therapy without PSA failure (A2). It was hypothesized that A2 failure may have a different prognosis. METHODSData for 2799 eligible patients from Radiation Therapy Oncology Group (RTOG) 9202 and RTOG 9413 were analyzed. BF was defined according to the 1997 American Society for Therapeutic Radiology and Oncology consensus definition as A1 for PSA failure or as A2 for the start of salvage hormone therapy before 3 consecutive PSA rises. RESULTSRates of all-cause mortality (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.5-2.0; P<.0001) and distant metastasis (DM; HR, 1.6; 95% CI, 1.3-2.0; P<.0001) were greater with A2 failure. The 5-year overall survival (OS) rates were 88.2% and 74.6% for A1 and A2, respectively (P<.0001), and the DM rates were 15.7% and 29.0%, respectively (P<.0001). The DM rate was greater at 5 years for A2 patients with DM as the first sign of failure versus patients with other A2 failures (87.3% vs 11.7%, P<.001), and this also correlated with worse OS at 5 years: 81.1% for A2 failure without DM and 52.8% with DM (P<.001). After the removal of patients with DM, the difference between A1 and A2 BF persisted for OS (P=.002) but not for DM (P=.16) CONCLUSIONSThese results suggest that patients with rising PSA levels alone have less risk than those with A2 failures; although DM was the largest contributor of adverse risk to A2 failure, it did not account for all excess risk in A2 failure. Cancer 2015;121:844-852. (c) 2014 American Cancer Society. After radiation therapy, biochemical failure is defined on the basis of either rising prostate-specific antigen levels or the initiation of salvage androgen ablation for other reasons. Patients started on salvage androgen therapy without meeting the criteria for rising prostate-specific antigen levels may have worse clinical outcomes; as such, those with rising prostate-specific antigen levels only may actually represent a more favorable group of patients. C1 [Hamstra, Daniel A.] Univ Michigan, Med Ctr, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. [Bae, Kyounghwa; Hu, Chen] Ctr Stat, Radiat Therapy Oncol Grp, Philadelphia, PA USA. [Hanks, Gerald] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Shipley, William U.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pan, Charlie C.] Bellin Canc Ctr, Green Bay, WI USA. [Roach, Mack, III] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Lawton, Colleen A.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Sandler, Howard M.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. EM dhamm@umich.edu FU Radiation Therapy Oncology Group grant from the National Cancer Institute [U10 CA21661]; Community Clinical Oncology Program grant from the National Cancer Institute [U10 CA37422]; NRG grant from the National Cancer Institute [U10 CA180822]; National Cancer Institute [U10 CA32115] FX This project was supported by Radiation Therapy Oncology Group grant U10 CA21661, Community Clinical Oncology Program grant U10 CA37422, NRG grant U10 CA180822, and statistical grant U10 CA32115 from the National Cancer Institute. NR 26 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD MAR 15 PY 2015 VL 121 IS 6 BP 844 EP 852 DI 10.1002/cncr.29146 PG 9 WC Oncology SC Oncology GA CD0HF UT WOS:000350750700008 PM 25410885 ER PT J AU Jabbour, EJ Garcia-Manero, G Strati, P Mishra, A Al Ali, NH Padron, E Lancet, J Kadia, T Daver, N O'Brien, S Steensma, DP Sekeres, MA Gore, SD Dezern, A Roboz, GJ List, AF Kantarjian, HM Komrokji, RS AF Jabbour, Elias J. Garcia-Manero, Guillermo Strati, Paolo Mishra, Asmita Al Ali, Najla H. Padron, Eric Lancet, Jeffrey Kadia, Tapan Daver, Naval O'Brien, Susan Steensma, David P. Sekeres, Mikkael A. Gore, Steven D. Dezern, Amy Roboz, Gail J. List, Alan F. Kantarjian, Hagop M. Komrokji, Rami S. TI Outcome of Patients With Low-Risk and Intermediate-1-Risk Myelodysplastic Syndrome After Hypomethylating Agent Failure SO CANCER LA English DT Article; Proceedings Paper CT 1st Palliative Care in Oncology Symposium CY OCT, 2014 CL Boston, MA DE myelodysplastic syndrome; low-risk; hypomethylating agent failure; survival ID AZACITIDINE TREATMENT FAILURE; PROGNOSTIC SCORING SYSTEM; PHASE-III; DECITABINE; LEUKEMIA; PROPOSAL; THERAPY AB BACKGROUNDThe hypomethylating agents (HMAs) azacitidine and decitabine are most commonly used to treat patients with higher-risk myelodysplastic syndromes (MDS). To the authors' knowledge, the prognosis of patients with low-risk and intermediate-1-risk MDS by the International Prognostic Scoring System (IPSS) after HMA failure has not been explored comprehensively. METHODSThe clinical characteristics and treatment outcome of 438 patients with low-risk and intermediate-1-risk MDS who were treated with HMAs were retrospectively analyzed. RESULTSUsing the International Working Group response criteria, the overall objective response to HMA was 35% with a median of 6 cycles of HMA administered, and the median response duration was 7 months. Only 7% of patients had disease that transformed into acute myeloid leukemia while receiving therapy. Of the 290 patients who were evaluable at the time of HMA failure, 77% remained in the lower-risk disease categories. On multivariate analysis, baseline neutropenia, intermediate-risk and poor-risk baseline karyotype, and lack of response to HMA were found to be independently associated with a higher risk of disease progression. With a median follow-up of 16 months, the median transformation-free survival and overall survival (OS) after HMA failure were 15 months and 17 months, respectively. On multivariate analysis, only The University of Texas MD Anderson Global Scoring System was found to be independently predictive of outcome, with patients with higher-risk categories having poor transformation-free survival (hazards ratio [HR], 1.5; P=.003) and OS (HR, 1.8; P=.002). The administration of salvage therapy was independently associated with better OS only (HR, 0.8; P=.01). CONCLUSIONSOutcomes of patients with lower-risk MDS after HMA failure are poor and the treatment of these patients remains an unmet medical need. OS is a reasonable primary endpoint for clinical studies targeting this population. Cancer 2015;121:876-882. (c) 2014 American Cancer Society. The outcomes of patients with lower-risk myelodysplastic syndromes after treatment failure with hypomethylating agents are poor, with a median survival of 17 months reported. Overall survival is a reasonable primary endpoint for clinical studies targeting this patient population. C1 [Jabbour, Elias J.; Garcia-Manero, Guillermo; Strati, Paolo; Kadia, Tapan; Daver, Naval; O'Brien, Susan; Kantarjian, Hagop M.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Mishra, Asmita; Padron, Eric; Lancet, Jeffrey; List, Alan F.; Komrokji, Rami S.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Med Oncol, Tampa, FL 33612 USA. [Al Ali, Najla H.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Malignant Hematol, Tampa, FL 33612 USA. [Steensma, David P.] Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02115 USA. [Sekeres, Mikkael A.] Cleveland Clin, Dept Hematol & Oncol, Cleveland, OH 44106 USA. [Gore, Steven D.] Yale Univ, Sch Med, Dept Hematol, New Haven, CT USA. [Dezern, Amy] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. [Roboz, Gail J.] Cornell Univ, Dept Hematol, New York, NY 10021 USA. EM ggarciam@mdanderson.org FU MDS Clinical Research Consortium sponsored by the Aplastic Anemia and MDS International Foundation; Edward P. Evans Foundation; University of Texas MD Anderson Cancer Center [CA016672]; Fundacion Ramon Areces (Madrid, Spain) FX Supported in part by the following grants: the MDS Clinical Research Consortium sponsored by the Aplastic Anemia and MDS International Foundation (made possible by funding from the Edward P. Evans Foundation); The University of Texas MD Anderson Cancer Center Support Grant CA016672; the Fundacion Ramon Areces (Madrid, Spain); and generous philanthropic contributions to The University of Texas MD Anderson Cancer Center Moon Shots Program. NR 21 TC 13 Z9 13 U1 0 U2 7 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 MAR 15 PY 2015 VL 121 IS 6 BP 876 EP 882 DI 10.1002/cncr.29145 PG 7 WC Oncology SC Oncology GA CD0HF UT WOS:000350750700012 PM 25410759 ER PT J AU El-Jawahri, AR Traeger, LN Kuzmuk, K Eusebio, JR Vandusen, HB Shin, JA Keenan, T Gallagher, ER Greer, JA Pirl, WF Jackson, VA Ballen, KK Spitzer, TR Graubert, TA McAfee, SL Dey, BR Chen, YBA Temel, JS AF El-Jawahri, Areej R. Traeger, Lara N. Kuzmuk, Kailyn Eusebio, Justin R. Vandusen, Harry B. Shin, Jennifer A. Keenan, Tanya Gallagher, Emily R. Greer, Joseph A. Pirl, William F. Jackson, Vicki A. Ballen, Karen K. Spitzer, Thomas R. Graubert, Timothy A. McAfee, Steven L. Dey, Bimalangshu R. Chen, Yi-Bin A. Temel, Jennifer S. TI Quality of Life and Mood of Patients and Family Caregivers During Hospitalization for Hematopoietic Stem Cell Transplantation SO CANCER LA English DT Article; Proceedings Paper CT 1st Palliative Care in Oncology Symposium CY OCT, 2014 CL Boston, MA DE quality of life (QOL); depression; mood; family caregivers; stem cell transplantation ID BONE-MARROW-TRANSPLANTATION; CANCER-PATIENTS; DEPRESSION; LEUKEMIA; IMPACT; CARE; AGE AB BACKGROUNDWe conducted a study to investigate the impact of hospitalization for hematopoietic stem cell transplantation (HCT) on the quality of life (QOL) and mood of patients and family caregivers (FC). METHODSWe conducted a longitudinal study of patients who were hospitalized for HCT and their FC. We assessed QOL (using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation) and mood (using the Hospital Anxiety and Depression Scale) at baseline (6 days before HCT), day +1, and day +8 of HCT. We administered the Medical Outcomes Study Health Survey Short Form-36 to examine FC QOL (Physical Component Scale and Mental Component Scale). To identify predictors of changes in QOL, we used multivariable linear mixed models. RESULTSWe enrolled 97% of eligible patients undergoing autologous (30 patients), myeloablative (30 patients), or reduced intensity (30 patients) allogeneic HCT. Patients' QOL markedly declined (mean Functional Assessment of Cancer Therapy-Bone Marrow Transplantation score, 109.6 to 96.0; P<.0001) throughout hospitalization. The percentage of patients with depression (Hospital Anxiety and Depression Scale-Depression score of >7) more than doubled from baseline to day +8 (15.6% to 37.8%; P<.0001), whereas the percentage of patients with anxiety remained stable (22.2%; P=.8). These results remained consistent when data were stratified by HCT type. Baseline depression (, -2.24; F, 42.2 [P<.0001]) and anxiety (, -0.63; F, 4.4 [P =.03]) were found to independently predict worse QOL throughout hospitalization. FC QOL declined during the patient's hospitalization (physical component scale: 83.1 to 79.6 [P =.03] and mental component scale: 71.6 to 67.4 [P =.04]). CONCLUSIONSPatients undergoing HCT reported a steep deterioration in QOL and substantially worsening depression during hospitalization. Baseline anxiety and depression predicted worse QOL during hospitalization, underscoring the importance of assessing pre-HCT psychiatric morbidity. Cancer 2015;121:951-959. (c) 2014 American Cancer Society. Patients undergoing hematopoietic stem cell transplantation reported a steep deterioration in quality of life and substantially worsening depression during hospitalization. Baseline anxiety and depression were found to predict worse quality of life during hospitalization, underscoring the importance of assessing psychiatric morbidity prior to hematopoietic stem cell transplantation. C1 [El-Jawahri, Areej R.; Shin, Jennifer A.; Keenan, Tanya; Gallagher, Emily R.; Ballen, Karen K.; Spitzer, Thomas R.; Graubert, Timothy A.; McAfee, Steven L.; Dey, Bimalangshu R.; Chen, Yi-Bin A.; Temel, Jennifer S.] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. [Traeger, Lara N.; Kuzmuk, Kailyn; Eusebio, Justin R.; Vandusen, Harry B.; Greer, Joseph A.; Pirl, William F.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Jackson, Vicki A.] Massachusetts Gen Hosp, Div Palliat Care, Boston, MA 02114 USA. EM ael-jawahri@partners.org OI Graubert, Timothy/0000-0002-7710-1171 FU Massachusetts General Hospital Cancer Center; National Institutes of Health [K24CA181253] FX Supported by funds from the Massachusetts General Hospital Cancer Center and National Institutes of Health grant K24CA181253 (to Dr. Temel). NR 27 TC 15 Z9 15 U1 0 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 MAR 15 PY 2015 VL 121 IS 6 BP 951 EP 959 DI 10.1002/cncr.29149 PG 9 WC Oncology SC Oncology GA CD0HF UT WOS:000350750700021 PM 25469752 ER PT J AU Passeri, JJ Elmariah, S Xu, K Inglessis, I Baker, JN Alu, M Kodali, S Leon, MB Svensson, LG Pibarot, P Fearon, WF Kirtane, AJ Vlahakes, GJ Palacios, IF Douglas, PS AF Passeri, Jonathan J. Elmariah, Sammy Xu, Ke Inglessis, Ignacio Baker, Joshua N. Alu, Maria Kodali, Susheel Leon, Martin B. Svensson, Lars G. Pibarot, Philippe Fearon, William F. Kirtane, Ajay J. Vlahakes, Gus J. Palacios, Igor F. Douglas, Pamela S. CA PARTNER Investigators TI Transcatheter aortic valve replacement and standard therapy in inoperable patients with aortic stenosis and low EF SO HEART LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; LOW EJECTION FRACTION; HIGH-RISK PATIENTS; BALLOON VALVULOPLASTY; CARDIAC-SURGERY; ECHOCARDIOGRAPHY; RECOMMENDATIONS; IMPLANTATION; MORTALITY; SURVIVAL AB Objectives The aims of this study were to evaluate the effect of left ventricular (LV) dysfunction on clinical outcomes after transcatheter aortic valve replacement (TAVR) and standard therapy for severe aortic stenosis (AS) and to assess LV ejection fraction (LVEF) recovery and its impact on subsequent clinical outcomes. Methods Cohort B of the Placement of AoRtic TraNscathetER Valves trial randomised 342 inoperable patients with severe AS to TAVR or standard therapy. We defined LV dysfunction as an LVEF < 50% and LVEF improvement as an absolute increase in LVEF >= 10% at 30 days. Results Baseline LV dysfunction did not affect survival after TAVR but was associated with increased cardiac mortality at 1 year with standard therapy (59.3% vs 45.8% with normal LVEF; HR=1.71 (95% CI 1.08 to 2.71); p= 0.02). In those with LV dysfunction, LVEF improvement occurred in 48.7% and 30.4% of TAVR and standard therapy patients, respectively (p= 0.08), and was independently predicted by relative wall thickness and receipt of TAVR. LVEF improvement with standard therapy portended reduced all-cause mortality at 1 year (28.6% vs 65.6% without LVEF improvement; HR=0.32 (95% CI 0.11 to 0.93); p=0.03) but not at 2 years. Conclusions In inoperable patients with severe AS, mild-to-moderate LV dysfunction is associated with higher cardiac mortality with standard therapy but not TAVR. A subset of patients undergoing standard therapy with LV dysfunction demonstrates LVEF improvement and favourable 1-year but not 2-year survival. TAVR improves survival and should be considered the standard of care for inoperable patients with AS and LVEF > 20%. C1 [Passeri, Jonathan J.; Elmariah, Sammy; Inglessis, Ignacio; Palacios, Igor F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA USA. [Elmariah, Sammy] Harvard Univ, Clin Res Inst, Boston, MA 02115 USA. [Xu, Ke; Alu, Maria; Kodali, Susheel; Leon, Martin B.; Kirtane, Ajay J.] Columbia Univ, Med Ctr, New York Presbyterian Hosp, Cardiovasc Res Fdn, New York, NY USA. [Baker, Joshua N.; Vlahakes, Gus J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiac Surg, Boston, MA USA. [Svensson, Lars G.] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA. [Pibarot, Philippe] Univ Laval, Quebec Heart & Lung Inst, Quebec City, PQ, Canada. [Fearon, William F.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Douglas, Pamela S.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. RP Passeri, JJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St,YAW 5700, Boston, MA 02114 USA. EM jpasseri@mgh.harvard.edu; selmariah@mgh.harvard.edu FU Edwards Lifesciences; American Heart Association [14 FTF20440012] FX The PARTNER Trial was supported by Edwards Lifesciences, and the protocol was designed collaboratively by the Steering Committee and Sponsor. This work was, in part, supported by the American Heart Association (14 FTF20440012 to SE). NR 33 TC 8 Z9 8 U1 2 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 EI 1468-201X J9 HEART JI Heart PD MAR 15 PY 2015 VL 101 IS 6 BP 463 EP 471 DI 10.1136/heartjnl-2014-306737 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CC4UY UT WOS:000350350800012 PM 25586156 ER PT J AU Sachs, GS Greenberg, WM Starace, A Lu, K Ruth, A Laszlovszky, I Nemeth, G Durgam, S AF Sachs, Gary S. Greenberg, William M. Starace, Anju Lu, Kaifeng Ruth, Adam Laszlovszky, Istvan Nemeth, Gyoergy Durgam, Suresh TI Cariprazine in the treatment of acute mania in bipolar trial I disorder: A double-blind, placebo-controlled, Phase III SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Cariprazine; Bipolar disorder; Mania; Antipsychotic; Dopamine D-3 receptors; Remission ID DOPAMINE D-3 RECEPTOR; ANTIPSYCHOTIC-DRUGS; RATING-SCALE; ANTIMANIC TREATMENTS; AFFINITY; SCHIZOPHRENIA; METAANALYSIS; ANTAGONISTS; DEPRESSION; VALIDITY AB Background: This Phase III, randomized, double-blind, placebo-controlled study investigated the efficacy and tolerability of flexibly-dosed cariprazine in patients with acute manic or mixed episodes associated with bipolar I disorder. Methods: Patients were randomized to 3 weeks of double-blind treatment with cariprazine 3-12 mg/day (n=158) or placebo (n=154). The primary efficacy parameter was change from baseline to Week 3 in Young Mania Rating Scale (YMRS) total score. The secondary efficacy parameter was change from baseline to Week 3 in Clinical Global Impressions-Severity (CGI-S) score. Results: Mean change from baseline to Week 3 in YMRS total score was significantly greater for patients receiving cariprazine 3-12 mg/day versus placebo (P=0.0004). Significant differences between groups in YMRS total score mean change were observed by Day 4 (first postbaseline assessment) and maintained throughout double-blind treatment (all assessments, P < 0.01). Cariprazine also demonstrated statistically significant superiority over placebo on YMRS response (>= 50% improvement: cariprazine, 58.9%; placebo, 44.1%; P=0.0097) and remission (YMRS total score < 12: cariprazine, 51.9%; placebo, 34.9%; P=0.0025) and mean change in CGI-S (P=0.0027) score and Positive and Negative Syndrome Scale (PANSS) (P=0.0035) total score. The most common cariprazine-related (>= 10% and twice placebo) treatment emergent adverse events (TEAEs) were akathisia, extrapyramiclal disorder, tremor, dyspepsia, and vomiting. Mean change from baseline in metabolic parameters were generally small and similar between groups. Limitations: Lack of active comparator arm; short duration of study. Conclusion: In this study, cariprazine 3-12 mg/day was effective and generally well tolerated in the treatment of manic and mixed episodes associated with bipolar l disorder. (C)2014 The Authors. Published by Elsevier B.V. C1 [Sachs, Gary S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greenberg, William M.; Starace, Anju; Lu, Kaifeng] Forest Res Inst, Jersey City, NJ USA. [Ruth, Adam] Prescott Med Commun Grp, Chicago, IL USA. [Laszlovszky, Istvan; Nemeth, Gyoergy] Gedeon Richter Plc, Budapest, Hungary. RP Sachs, GS (reprint author), Massachusetts Gen Hosp, 15 Parkman St, Boston, MA 02114 USA. EM sachsg@aol.com FU Forest Laboratories, Inc.; Actavis Plc (New York, New York); Gedeon Richter Plc (Budapest, Hungary) FX This study was supported by funding from Forest Laboratories, Inc., a subsidiary of Actavis Plc (New York, New York), and Gedeon Richter Plc (Budapest, Hungary). Forest Laboratories, Inc. and Gedeon Richter Plc were involved in the study design, collection (via contracted clinical investigator sites), analysis, and interpretation of data, and the decision to present these results. NR 37 TC 21 Z9 23 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAR 15 PY 2015 VL 174 BP 296 EP 302 DI 10.1016/j.jad.2014.11.018 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CC0CY UT WOS:000350003800041 PM 25532076 ER PT J AU Pietrzak, RH Tsai, J Armour, C Mota, N Harpaz-Rotem, I Southwick, SM AF Pietrzak, Robert H. Tsai, Jack Armour, Cherie Mota, Natalie Harpaz-Rotem, Ilan Southwick, Steven M. TI Functional significance of a novel 7-factor model of DSM-5 PTSD symptoms: Results from the National Health and Resilience in Veterans Study SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Posttraumatic stress disorder; Veterans; Trauma; Symptomatology; Functioning ID POSTTRAUMATIC-STRESS-DISORDER; QUALITY-OF-LIFE; DEPRESSION; ANXIETY AB Background: While post:traumatic stress disorder (PTSD) symptoms in the recently published Diagnostic. and Statistical Manual of Mental Disorders, Filth Edition (DSM-5) are clustered into four factors, emerging confirmatory factor analytic studies suggest that this disorder is best characterized by seven symptom clusters, including re-experiencing, avoidance, negative affect, anhedonia, externalizing behaviors, and anxious and dysphoric arousal symptoms. To date, however, data are lacking regarding the relation between this novel model of DSM-5 PTSD symptoms and measures of clinical significance in this population (e.g., functioning). Methods: Using data from the National Health and Resilience in Veterans Study (NHRVS), a contemporary, nationally representative sample of 1484 U.S. veterans, we evaluated clinical and functional Correlates of a novel 7-factor model of DSM-5 PTSD symptoms. Results: Differential patterns of associations were observed between DSM-5 PTSD symptom clusters, and psychiatric comorbidities, suicidal ideation, hostility, and functioning and quality of life. Anhedonia symptoms, in particular, were strongly related to current depression, as well as reduced mental Functioning and quality of life. Externalizing behaviors were most strongly related to hostility, supporting the convergent validity of this construct. Limitations: Cross-sectional design and employment of self-report measures. Conclusions: These results suggest that a more refined 7-factor model of DSM-5 PTSD symptoms may provide greater specificity in understanding associations with comorbid psychopathology, suicidal ideation, and functioning and quality of life in US. veterans. They further suggest that prevention and treatment efforts that target distinct aspects of the PTSD phenotype may be more effective in mitigating key clinical and functional outcomes in this population. Published by Elsevier B.V. C1 [Pietrzak, Robert H.; Harpaz-Rotem, Ilan; Southwick, Steven M.] US Dept Vet Affairs, Natl Ctr Posttraumut Stress Disorder, Clin Neurosci Div, VA Connecticut Healthcare Syst, West Haven, CT USA. [Pietrzak, Robert H.; Tsai, Jack; Mota, Natalie; Harpaz-Rotem, Ilan; Southwick, Steven M.] Yale Univ, Dept Psychiat, West Haven, CT 06516 USA. [Tsai, Jack] US Dept Vet Affairs, New England Mental Illness Res Educ & Clin Ctr, West Haven, CT USA. [Armour, Cherie] Univ Ulster, Psychol Res Inst, Coleraine BT52 1SA, Londonderry, North Ireland. RP Pietrzak, RH (reprint author), Yale Univ, Dept Psychiat, 950 Campbell Ave 151E, West Haven, CT 06516 USA. EM robert.pietrzak@yale.edu OI Armour, Cherie/0000-0001-7649-3874 FU U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder FX The National Health and Resilience in Veterans Study (NHRVS) and preparation of this report was supported by the U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder and a private donation. NR 22 TC 19 Z9 19 U1 2 U2 24 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAR 15 PY 2015 VL 174 BP 522 EP 526 DI 10.1016/j.jad.2014.12.007 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CC0CY UT WOS:000350003800071 PM 25556669 ER PT J AU Cadoni, S Falt, P Gallittu, P Liggi, M Mura, D Smajstrla, V Erriu, M Leung, FW AF Cadoni, S. Falt, P. Gallittu, P. Liggi, M. Mura, D. Smajstrla, V. Erriu, M. Leung, F. W. TI COMPARISON OF METHODS FOR LUMINAL DISTENTION FOR ON-DEMAND SEDATION COLONOSCOPY: AIR INSUFFLATION, CARBON DIOXIDE AND WATER-AIDED COLONOSCOPY: A 2-CENTER RANDOMIZED CONTROLLED TRIAL SO DIGESTIVE AND LIVER DISEASE LA English DT Meeting Abstract C1 [Cadoni, S.; Gallittu, P.; Liggi, M.; Mura, D.] S Barbara Hosp, Digest Endoscopy Unit, Iglesias, CI, Italy. [Falt, P.; Smajstrla, V.] Vitkovice Hosp, Ctr Digest Dis, Ostrava, Czech Republic. [Erriu, M.] Univ Cagliari, Dept Surg Sci, Cagliari, Italy. [Leung, F. W.] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Los Angeles, CA 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 1590-8658 EI 1878-3562 J9 DIGEST LIVER DIS JI Dig. Liver Dis. PD MAR 15 PY 2015 VL 47 SU 2 MA OC.02.2 BP E75 EP E76 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V46MS UT WOS:000209888900018 ER PT J AU Shimada, YJ Scirica, BM AF Shimada, Yuichi J. Scirica, Benjamin M. TI Long-Term Management and Unmet Needs After an Acute Coronary Syndrome Event SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; T-WAVE ALTERNANS; DUAL ANTIPLATELET THERAPY; ASSOCIATION TASK-FORCE; HEART-RATE-VARIABILITY; SUDDEN CARDIAC DEATH; DRUG-ELUTING STENT; CARDIOVERTER-DEFIBRILLATOR; BAROREFLEX SENSITIVITY; PRACTICE GUIDELINES C1 [Shimada, Yuichi J.; Scirica, Benjamin M.] Brigham & Womens Hosp, Cardiovasc Div, Boston, MA 02115 USA. [Scirica, Benjamin M.] Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div, Boston, MA 02115 USA. RP Scirica, BM (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div, 350 Longwood Ave, Boston, MA 02115 USA. EM bscirica@partners.org OI Shimada, Yuichi/0000-0002-3494-307X FU AstraZeneca LP FX Publication of this article was supported by funding from AstraZeneca LP. NR 33 TC 1 Z9 1 U1 0 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 MAR 14 PY 2015 VL 115 IS 5 SU S BP 37 EP 43 DI 10.1016/j.amjcard.2015.01.005 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE0HY UT WOS:000351486300005 PM 25728972 ER PT J AU Valenza, G Garcia, RG Citi, L Scilingo, EP Tomaz, CA Barbieri, R AF Valenza, Gaetano Garcia, Ronald G. Citi, Luca Scilingo, Enzo P. Tomaz, Carlos A. Barbieri, Riccardo TI Nonlinear digital signal processing in mental health: characterization of major depression using instantaneous entropy measures of heartbeat dynamics SO FRONTIERS IN PHYSIOLOGY LA English DT Article DE nonlinear; heart rate variability; instantaneous entropy; point process; Wiener-Volterra series; Laguerre expansion ID RATE-VARIABILITY; DISORDERS; MECHANISMS; COMPLEXITY; ILLNESS; STATES; SCALE AB Nonlinear digital signal processing methods that address system complexity have provided useful computational tools for helping in the diagnosis and treatment of a wide range of pathologies. More specifically, nonlinear measures have been successful in characterizing patients with mental disorders such as Major Depression (MD). In this study, we propose the use of instantaneous measures of entropy, namely the inhomogeneous point-process approximate entropy (ipApEn) and the inhomogeneous point-process sample entropy (ipSampEn), to describe a novel characterization of MD patients undergoing affective elicitation. Because these measures are built within a nonlinear point-process model, they allow for the assessment of complexity in cardiovascular dynamics at each moment in time. Heartbeat dynamics were characterized from 48 healthy controls and 48 patients with MD while emotionally elicited through either neutral or arousing audiovisual stimuli. Experimental results coming from the arousing tasks show that ipApEn measures are able to instantaneously track heartbeat complexity as well as discern between healthy subjects and MD patients. Conversely, standard heart rate variability (HRV) analysis performed in both time and frequency domains did not show any statistical significance. We conclude that measures of entropy based on nonlinear point-process models might contribute to devising useful computational tools for care in mental health. C1 [Valenza, Gaetano; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Valenza, Gaetano] MIT, Cambridge, MA 02139 USA. [Valenza, Gaetano; Scilingo, Enzo P.] Univ Pisa, Dept Informat Engn, Res Ctr E Piaggio, Pisa, Italy. [Garcia, Ronald G.] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Garcia, Ronald G.] Univ Santander, Masira Res Inst, Sch Med, Dept Psychiat, Bucaramanga, Colombia. [Citi, Luca] Univ Essex, Sch Comp Sci & Elect Engn, Colchester CO4 3SQ, Essex, England. [Tomaz, Carlos A.] Univ Brasilia, Lab Neurosci & Behav, Brasilia, DF, Brazil. RP Barbieri, R (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, Crit Care, 55 Fruit St,Jackson 4, Boston, MA 02114 USA. EM barbieri@neurostat.mit.edu OI Barbieri, Riccardo/0000-0001-9381-3833; Garcia, Ronald Gerardo/0000-0002-8325-9944; Scilingo, Enzo Pasquale/0000-0003-2588-4917; Valenza, Gaetano/0000-0001-6574-1879 FU Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; European Union [601165]; Colombian Institute for the Development of Science and Technology "Colciencias" [6566-408-20391] FX This study received partial funding from the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA, from the European Union Seventh Framework Programme FP7/2007-2013 under Grant No. 601165 of the project "WEARHAP," and from the Colombian Institute for the Development of Science and Technology "Colciencias" (Project No. 6566-408-20391). NR 36 TC 3 Z9 3 U1 2 U2 6 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-042X J9 FRONT PHYSIOL JI Front. Physiol. PD MAR 13 PY 2015 VL 6 AR 74 DI 10.3389/fphys.2015.00074 PG 8 WC Physiology SC Physiology GA CG0DG UT WOS:000352936200001 PM 25821435 ER PT J AU Choi, YE Park, E AF Choi, Young Eun Park, Eunmi TI Ferulic acid in combination with PARP inhibitor sensitizes breast cancer cells as chemotherapeutic strategy SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Ferulic acid; ABT-888; Breast cancer cells; Homologous-recombination repair ID MAMMALIAN-CELLS; REPAIR; CISPLATIN; MICE AB Homologous-recombination (HR)-dependent repair defective cells are hypersensitive to poly (ADPribose) polymerase (PARP) inhibitors. Combinations of defective HR pathway and PARP inhibitors have been an effective chemotherapeutic modality. We previously showed that knockdown of the WD40-repeat containing protein, Uafl, causes an HR repair defect in mouse embryo fibroblast cells and therefore, increases sensitivity to PARP inhibitor, ABT-888. Similarly, here, we show that ferulic acid reduces HR repair, inhibits RAD 51 foci formation, and accumulates gamma-H2AX in breast cancer cells. Moreover, ferulic acid, when combined with ABT-888, renders breast cancer cells become hypersensitive to ABT-888. Our study indicates that ferulic acid in combination with ABT-888 treatment may serve as an effective combination chemotherapeutic agent as a natural bioactive compound. (C) 2015 Elsevier Inc. All rights reserved. C1 [Choi, Young Eun] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Park, Eunmi] Hannam Univ, Sch Life Sci & Nanotechnol, Dept Food & Nutr, Taejon 305811, South Korea. RP Park, E (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM eunmi_park@hnu.kr NR 18 TC 7 Z9 8 U1 3 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 13 PY 2015 VL 458 IS 3 BP 520 EP 524 DI 10.1016/j.bbrc.2015.01.147 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CE2QD UT WOS:000351659200012 PM 25677620 ER PT J AU Cai, Y Hirata, A Nakayama, S VanderLaan, PA Levantini, E Yamamoto, M Hirai, H Wong, KK Costa, DB Watanabe, H Kobayashi, SS AF Cai, Yi Hirata, Ayako Nakayama, Sohei VanderLaan, Paul A. Levantini, Elena Yamamoto, Mihoko Hirai, Hideyo Wong, Kwok-Kin Costa, Daniel B. Watanabe, Hideo Kobayashi, Susumu S. TI CCAAT/Enhancer Binding Protein beta Is Dispensable for Development of Lung Adenocarcinoma SO PLOS ONE LA English DT Article ID EPITHELIAL-CELL PROLIFERATION; C/EBP-BETA; TRANSCRIPTION FACTORS; DIFFERENTIAL EXPRESSION; DOWN-REGULATION; CANCER-THERAPY; MAMMARY-GLAND; IN-VIVO; ALPHA; FAMILY AB Lung cancer is the leading cause of cancer death worldwide. Although disruption of normal proliferation and differentiation is a vital component of tumorigenesis, the mechanisms of this process in lung cancer are still unclear. A transcription factor, C/EBP beta is a critical regulator of proliferation and/or differentiation in multiple tissues. In lung, C/EBP beta is expressed in alveolar pneumocytes and bronchial epithelial cells; however, its roles on normal lung homeostasis and lung cancer development have not been well described. Here we investigated whether C/EBP beta is required for normal lung development and whether its aberrant expression and/or activity contribute to lung tumorigenesis. We showed that C/EBP beta was expressed in both human normal pneumocytes and lung adenocarcinoma cell lines. We found that overall lung architecture was maintained in Cebpb knockout mice. Neither overexpression of nuclear C/EBP beta nor suppression of CEBPB expression had significant effects on cell proliferation. C/EBP beta expression and activity remained unchanged upon EGF stimulation. Furthermore, deletion of Cebpb had no impact on lung tumor burden in a lung specific, conditional mutant EGFR lung cancer mouse model. Analyses of data from The Cancer Genome Atlas (TCGA) revealed that expression, promoter methylation, or copy number of CEBPB was not significantly altered in human lung adenocarcinoma. Taken together, our data suggest that C/EBP beta is dispensable for development of lung adenocarcinoma. C1 [Cai, Yi; Hirata, Ayako; Nakayama, Sohei; Levantini, Elena; Yamamoto, Mihoko; Costa, Daniel B.; Kobayashi, Susumu S.] Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. [VanderLaan, Paul A.] Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Levantini, Elena] CNR, Natl Res Council, Inst Biomed Technol, I-56100 Pisa, Italy. [Hirata, Ayako; Hirai, Hideyo] Kyoto Univ Hosp, Dept Transfus Med & Cell Therapy, Kyoto 606, Japan. [Wong, Kwok-Kin; Watanabe, Hideo] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Watanabe, Hideo] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA USA. [Kobayashi, Susumu S.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Watanabe, H (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM hideo_watanabe@dfci.harvard.edu; skobayas@bidmc.harvard.edu OI Costa, Daniel/0000-0002-0689-395X FU National Institution of Health [R00CA126026, R01CA169259]; Harvard Stem Cell Institute [DP-0110-12-00]; Lung Cancer Foundation of America-International Association; American Cancer Society [RSG-13-047, RSG-11-186]; Bonnie J. Addario Lung Cancer Foundation FX Funding: This work was supported by National Institution of Health grants (R00CA126026 and R01CA169259 to S. S. K.); Harvard Stem Cell Institute (DP-0110-12-00); an Lung Cancer Foundation of America-International Association to Study Lung Cancer grant (D. B. C.); an American Cancer Society grant (RSG-13-047 to S. S. K. and RSG-11-186 to D. B. C.); and Bonnie J. Addario Lung Cancer Foundation grant (S. N.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 0 Z9 0 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 13 PY 2015 VL 10 IS 3 AR e0120647 DI 10.1371/journal.pone.0120647 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CD7NO UT WOS:000351277500132 PM 25767874 ER PT J AU Weber, GF Chousterman, BG He, S Fenn, AM Nairz, M Anzai, A Brenner, T Uhle, F Iwamoto, Y Robbins, CS Noiret, L Maier, SL Zonnchen, T Rahbari, NN Scholch, S Ameln, AKV Chavakis, T Weitz, J Hofer, S Weigand, MA Nahrendorf, M Weissleder, R Swirski, FK AF Weber, Georg F. Chousterman, Benjamin G. He, Shun Fenn, Ashley M. Nairz, Manfred Anzai, Atsushi Brenner, Thorsten Uhle, Florian Iwamoto, Yoshiko Robbins, Clinton S. Noiret, Lorette Maier, Sarah L. Zoennchen, Tina Rahbari, Nuh N. Schoelch, Sebastian Ameln, Anne Klotzsche-von Chavakis, Triantafyllos Weitz, Juergen Hofer, Stefan Weigand, Markus A. Nahrendorf, Matthias Weissleder, Ralph Swirski, Filip K. TI Interleukin-3 amplifies acute inflammation and is a potential therapeutic target in sepsis SO SCIENCE LA English DT Article ID B-CELLS PROTECT; UNITED-STATES; SEPTIC SHOCK; IN-VITRO; IMMUNOSUPPRESSION; FAILURE; BIOLOGY; TRIAL; CSF AB Sepsis is a frequently fatal condition characterized by an uncontrolled and harmful host reaction to microbial infection. Despite the prevalence and severity of sepsis, we lack a fundamental grasp of its pathophysiology. Here we report that the cytokine interleukin-3 (IL-3) potentiates inflammation in sepsis. Using a mouse model of abdominal sepsis, we showed that innate response activator B cells produce IL-3, which induces myelopoiesis of Ly-6C(high) monocytes and neutrophils and fuels a cytokine storm. IL-3 deficiency protects mice against sepsis. In humans with sepsis, high plasma IL-3 levels are associated with high mortality even after adjusting for prognostic indicators. This study deepens our understanding of immune activation, identifies IL-3 as an orchestrator of emergency myelopoiesis, and reveals a new therapeutic target for treating sepsis. C1 [Weber, Georg F.; Chousterman, Benjamin G.; He, Shun; Fenn, Ashley M.; Nairz, Manfred; Anzai, Atsushi; Iwamoto, Yoshiko; Robbins, Clinton S.; Noiret, Lorette; Nahrendorf, Matthias; Weissleder, Ralph; Swirski, Filip K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02163 USA. [Weber, Georg F.; Maier, Sarah L.; Zoennchen, Tina; Rahbari, Nuh N.; Schoelch, Sebastian; Weitz, Juergen] Tech Univ Dresden, Dept Visceral Thorac & Vasc Surg, D-01062 Dresden, Germany. [Brenner, Thorsten; Uhle, Florian; Hofer, Stefan; Weigand, Markus A.] Heidelberg Univ, Dept Anesthesiol, Heidelberg, Germany. [Ameln, Anne Klotzsche-von; Chavakis, Triantafyllos] Tech Univ Dresden, Dept Clin Pathobiochem, D-01062 Dresden, Germany. [Ameln, Anne Klotzsche-von; Chavakis, Triantafyllos] Tech Univ Dresden, Inst Clin Chem & Lab Med, D-01062 Dresden, Germany. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Weber, GF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02163 USA. EM georg.weber@uniklinikum-dresden.de; fswirski@mgh.harvard.edu RI He, Shun/K-7448-2014; OI Scholch, Sebastian/0000-0003-0012-3177 FU NIH [5R01HL095612, R56-AI104695]; Massachusetts General Hospital Howard M. Goodman Fellowship; German Research Foundation [WE4892/1-2, WE4892/3-1]; Societe Francaise d'Anesthesie-Reanimation (SFAR); Institut Servier; Fondation Groupe Pasteur Mutualite; Fulbright Scholarships (Monahan Foundation); Fulbright Scholarships (Harvard French Scholarship Fund); Erwin Schrodinger Fellowship of the Austrian Science Fund FWF [J3486-B13] FX We thank M. Greene for secretarial assistance, M. Waring and A. Chicoine for sorting cells, and K. Joyes for editing the manuscript. The data presented in this manuscript are tabulated in the main paper and in the supplementary materials. The General Hospital Corporation has filed a patent application (61/973,458) with the U.S. Patent and Trademark Office entitled "Agents and Methods for Diagnosing and Treating Sepsis," which names F.K.S. and G.F.W. as inventors. Il3-/- mice are available from Riken, Japan, under a materials transfer agreement. This work was supported by NIH grants 5R01HL095612 and R56-AI104695 and the Massachusetts General Hospital Howard M. Goodman Fellowship (F.K.S.). G.F.W. was supported by the German Research Foundation (WE4892/1-2 and 3-1). B.G.C. was supported by the Societe Francaise d'Anesthesie-Reanimation (SFAR), Institut Servier, Fondation Groupe Pasteur Mutualite, and Fulbright Scholarships (Monahan Foundation and Harvard French Scholarship Fund). M.N. was supported by an Erwin Schrodinger Fellowship of the Austrian Science Fund FWF (J3486-B13). The authors declare no conflicts of interest. NR 32 TC 39 Z9 40 U1 10 U2 49 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 MAR 13 PY 2015 VL 347 IS 6227 BP 1260 EP 1265 DI 10.1126/science.aaa4268 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CD1GZ UT WOS:000350824300041 PM 25766237 ER PT J AU Wigley, F Friday, RP Shepard, JAO Nazarian, RM AF Wigley, Fredrick Friday, Robert P. Shepard, Jo-Anne O. Nazarian, Rosalynn M. TI Case 8-2015: A 68-Year-Old Man with Multiple Myeloma, Skin Tightness, Arthralgias, and Edema SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NEPHROGENIC SYSTEMIC FIBROSIS; RENAL-FAILURE; SCLEROMYXEDEMA; SCLERODERMA; SCLEROSIS; ANTIBODIES; DISORDERS; MUCINOSIS; PATIENT; DISEASE C1 [Wigley, Fredrick] Johns Hopkins Univ, Sch Med, Dept Med, Johns Hopkins Hosp, Baltimore, MD 21205 USA. [Wigley, Fredrick] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Friday, Robert P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Shepard, Jo-Anne O.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Nazarian, Rosalynn M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Friday, Robert P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Shepard, Jo-Anne O.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Nazarian, Rosalynn M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wigley, F (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Johns Hopkins Hosp, Baltimore, MD 21205 USA. FU Eiger Biopharmaceuticals; Actelion Pharmaceuticals; MedImmune; Novartis; United Therapeutics; CSL Behring; Sanofi Aventis; Hoffmann-La Roche FX Dr. Wigley reports receiving consulting fees from Eiger Bio-pharmaceuticals and grant support from Actelion Pharmaceuticals, MedImmune, Novartis, United Therapeutics, CSL Behring, Sanofi Aventis, and Hoffmann-La Roche; and Dr. Shepard, receiving consulting fees for providing expert testimony in a legal case regarding thoracic imaging. No other potential conflict of interest relevant to this article was reported. NR 27 TC 1 Z9 1 U1 1 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 12 PY 2015 VL 372 IS 11 BP 1056 EP 1067 DI 10.1056/NEJMcpc1409840 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA CD0XK UT WOS:000350797300012 PM 25760359 ER PT J AU Papavasileiou, E Lobo, AM AF Papavasileiou, Evangelia Lobo, Ann-Marie TI Birdshot chorioretinopathy in a male patient with facioscapulohumeral muscular dystrophy SO JOURNAL OF OPHTHALMIC INFLAMMATION AND INFECTION LA English DT Article DE Birdshot chorioretinopathy; Facioscapulohumeral muscular dystrophy ID COATS-DISEASE; RETINOCHOROIDOPATHY; ASSOCIATION AB Background: We report a case of birdshot chorioretinopathy (BSCR) in a patient with facioscapulohumeral muscular dystrophy (FSHD). A 40-year-old male with history of facioscapulohumeral muscular dystrophy with significant facial diplegia and lagophthalmos presents for an evaluation of bilateral choroiditis with vasculitis and optic disc edema. Clinical examination included fundus and autofluorescence photographs, fluorescein angiography, and optical coherence tomography. To our knowledge, this patient represents the first reported case of birdshot chorioretinopathy with facioscapulohumeral muscular dystrophy. Patients with FSHD can present with ocular findings and should be screened with dilated fundus examinations for retinal vascular changes and posterior uveitis. C1 [Papavasileiou, Evangelia; Lobo, Ann-Marie] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02163 USA. [Lobo, Ann-Marie] Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. RP Lobo, AM (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02163 USA. EM Ann-Marie_Lobo@meei.harvard.edu NR 23 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1869-5760 J9 J OPHTHALMIC INFLAMM JI J. Ophthalmic Inflamm. Infect. PD MAR 12 PY 2015 VL 5 AR 7 DI 10.1186/s12348-014-0030-z PG 4 WC Ophthalmology SC Ophthalmology GA CZ2JW UT WOS:000366932400001 PM 25861398 ER PT J AU Sarantopoulos, S Ritz, J AF Sarantopoulos, Stefanie Ritz, Jerome TI Aberrant B-cell homeostasis in chronic GVHD SO BLOOD LA English DT Article ID VERSUS-HOST-DISEASE; CD4(+) T-CELLS; HISTOCOMPATIBILITY ANTIGEN DBY; SYSTEMIC-LUPUS-ERYTHEMATOSUS; REGULATORY B10 CELLS; BRONCHIOLITIS OBLITERANS; ACTIVATING FACTOR; TRANSPLANTATION; BAFF; MEMORY AB Recent studies have compelled further interest in the potential pathological role of B cells in chronic graft-versus-host disease (cGVHD). In patients with cGVHD, B cells are activated and primed for survival viaB-cell activating factor and B-cell receptor-associated pathways. Understanding the signaling pathways that drive immune pathology in cGVHD will facilitate the development of new strategies to selectively target aberrantly activated B cells and restore normal B-cell homeostasis after allogeneic stem cell transplantation. C1 [Sarantopoulos, Stefanie] Duke Univ, Dept Med, Duke Canc Inst, Div Cell Therapy & Hematol Malignancies, Durham, NC USA. [Ritz, Jerome] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Sarantopoulos, S (reprint author), Duke Canc Inst, Div Cell Therapy & Hematol Malignancies, Box 3961 Jones Bldg,Room 152, Durham, NC 27710 USA. EM stefanie.sarantopoulos@duke.edu; jerome_ritz@dfci.harvard.edu OI Ritz, Jerome/0000-0001-5526-4669 FU National Institutes of Health, National Heart, Lung, and Blood Institute [K08HL107756]; National Cancer Institute [P01CA142106] FX This work was supported by grants from the National Institutes of Health, National Heart, Lung, and Blood Institute (K08HL107756) and National Cancer Institute (P01CA142106). NR 67 TC 23 Z9 24 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAR 12 PY 2015 VL 125 IS 11 BP 1703 EP 1707 DI 10.1182/blood-2014-12-567834 PG 5 WC Hematology SC Hematology GA CI3BF UT WOS:000354621700008 PM 25645355 ER PT J AU Chen, SD Sanjana, NE Zheng, KJ Shalem, O Lee, K Shi, X Scott, DA Song, J Pan, JQ Weissleder, R Lee, H Zhang, F Sharp, PA AF Chen, Sidi Sanjana, Neville E. Zheng, Kaijie Shalem, Ophir Lee, Kyungheon Shi, Xi Scott, David A. Song, Jun Pan, Jen Q. Weissleder, Ralph Lee, Hakho Zhang, Feng Sharp, Phillip A. TI Genome-wide CRISPR Screen in a Mouse Model of Tumor Growth and Metastasis SO CELL LA English DT Article ID IN-VIVO; BREAST-CANCER; HUMAN-CELLS; DNA; IMMUNITY; RNA; PROVIDES; SYSTEMS; COMPLEX; CAS9 AB Genetic screens are powerful tools for identifying genes responsible for diverse phenotypes. Here we describe a genome-wide CRISPR/Cas9-mediated loss-of-function screen in tumor growth and metastasis. We mutagenized a non-metastatic mouse cancer cell line using a genome-scale library with 67,405 single-guide RNAs (sgRNAs). The mutant cell pool rapidly generates metastases when transplanted into immunocompromised mice. Enriched sgRNAs in lung metastases and late-stage primary tumors were found to target a small set of genes, suggesting that specific loss-of-function mutations drive tumor growth and metastasis. Individual sgRNAs and a small pool of 624 sgRNAs targeting the top-scoring genes from the primary screen dramatically accelerate metastasis. In all of these experiments, the effect of mutations on primary tumor growth positively correlates with the development of metastases. Our study demonstrates Cas9-based screening as a robust method to systematically assay gene phenotypes in cancer evolution in vivo. C1 [Chen, Sidi; Sharp, Phillip A.] David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Chen, Sidi; Sharp, Phillip A.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Chen, Sidi; Sanjana, Neville E.; Zheng, Kaijie; Shalem, Ophir; Shi, Xi; Scott, David A.; Pan, Jen Q.; Zhang, Feng] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Sanjana, Neville E.; Zheng, Kaijie; Shalem, Ophir; Shi, Xi; Scott, David A.; Pan, Jen Q.; Zhang, Feng] Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Sanjana, Neville E.; Zhang, Feng] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Sanjana, Neville E.; Zhang, Feng] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Sanjana, Neville E.; Zhang, Feng] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Lee, Kyungheon; Song, Jun; Weissleder, Ralph; Lee, Hakho] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Zhang, F (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM zhang@broadinstitute.org; sharppa@mit.edu RI Lee, Kyungheon/E-3863-2013; OI Sanjana, Neville/0000-0002-1504-0027 FU United States Public Health Service from the NIH [R01-CA133404]; MIT-Harvard Center for Cancer Nanotechnology Excellence from the National Cancer Institute [U54 CA151884]; Skolkovo Foundation; Koch Institute from the National Cancer Institute [P30-CA14051]; NIH through NIMH [5DP1-MH100706]; NIDDK [5R01-DK097768]; National Science Foundation; Keck foundation; New York Stem Cell foundation; Damon Runyon foundation; Searle Scholars foundation; Merkin foundation; Vallee foundation; Bob Metcalfe; Dale Frey Award for Breakthrough Scientists; Simons Center for the Social Brain Postdoctoral Fellowship; NIH NHGRI [K99-HG008171]; NIH [U54 CA151884]; NSF; Department of Defense [OCRP W81XWH-14-1-0279] FX We thank R. Weinberg and R. Kerbel for critically reading the manuscript; the entire P.A.S. lab and F.Z. lab, L. Cong, T. Kelly, X. Ni, M. Nobel, J. Boehm, A. Tsherniak, S. Levine, M. Cornwall-Brady, S. Malstrom, M. Jennings, E. Vasile, C. Whittaker, K. Cormier, R. Bronson, and colleagues at the Koch Institute, Broad Institute, McGovern Institute, and Department of Biology for technical assistance and/or discussion; the Swanson Biotechnology Center for technical support (Genomics, Animal Imaging and Preclinical Testing, Bioinformatics and Computing, Microscopy, Flow Cytometry, Microscopy, and Histology, in particular). This work is supported by grants to P.A.S., including a United States Public Health Service grant R01-CA133404 from the NIH, an MIT-Harvard Center for Cancer Nanotechnology Excellence Grant U54 CA151884 from the National Cancer Institute, a generous gift from the Marie D. and Pierre Casimir-Lambert Fund, an SkTech/MIT Initiative Grant from the Skolkovo Foundation, and the Koch Institute Support (core) grant P30-CA14051 from the National Cancer Institute. F.Z. is supported by the NIH through NIMH grant 5DP1-MH100706) and NIDDK grant 5R01-DK097768; a Waterman Award from the National Science Foundation; the Keck, New York Stem Cell, Damon Runyon, Searle Scholars, Merkin, and Vallee foundations; and Bob Metcalfe. F.Z. is a New York Stem Cell Foundation Robertson Investigator. S. C. is a Damon Runyon Cancer Research Fellow (DRG-2117-12) and also supported by the Dale Frey Award for Breakthrough Scientists. N.E.S. is supported by a Simons Center for the Social Brain Postdoctoral Fellowship and NIH NHGRI award K99-HG008171. O.S. is a fellow of the Klarman Cell Observatory. R.W. is supported by NIH grant U54 CA151884. D. A. S. is supported by a NSF Graduate Research Fellowship. H.L. is supported by Department of Defense grant OCRP W81XWH-14-1-0279. CRISPR reagents (plasmids and libraries) are available to the academic community through Addgene. F.Z. is a co-founder of Editas Medicine and a scientific advisor for Editas Medicine and Horizon Discovery. NR 51 TC 107 Z9 122 U1 35 U2 168 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 MAR 12 PY 2015 VL 160 IS 6 BP 1246 EP 1260 DI 10.1016/j.cell.2015.02.038 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CE6MT UT WOS:000351951800022 PM 25748654 ER PT J AU Nazha, B Salloum, RH Fahed, AC Nabulsi, M AF Nazha, Bassel Salloum, Rony H. Fahed, Akl C. Nabulsi, Mona TI Students' Perceptions of Peer-Organized Extra-Curricular Research Course during Medical School: A Qualitative Study SO PLOS ONE LA English DT Article ID ASSOCIATION; EDUCATION AB Early integration of research education into medical curricula is crucial for evidence-based practice. Yet, many medical students are graduating with no research experience due to the lack of such integration in their medical school programs. The purpose of this study was to explore the impact of a peer-organized, extra-curricular research methodology course on the attitudes of medical students towards research and future academic careers. Twenty one medical students who participated in a peer-organized research course were enrolled in three focus group discussions to explore their experiences, perceptions and attitudes towards research after the course. Discussions were conducted using a semi-structured interview guide, and were transcribed and thematically analyzed for major and minor themes identification. Our findings indicate that students' perceptions of research changed after the course from being difficult initially to becoming possible. Participants felt that their research skills and critical thinking were enhanced and that they would develop research proposals and abstracts successfully. Students praised the peer-assisted teaching approach as being successful in enhancing the learning environment and filling the curricular gap. In conclusion, peer-organized extra-curricular research courses may be a useful option to promote research interest and skills of medical students when gaps in research education in medical curricula exist. C1 [Nazha, Bassel] NorthShore LIJ Staten Isl Univ Hosp, Dept Internal Med, Staten Isl, NY USA. [Salloum, Rony H.] Cleveland Clin, Dept Neurosci, Lerner Res Inst, Cleveland, OH 44106 USA. [Fahed, Akl C.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Nabulsi, Mona] Amer Univ Beirut, Dept Pediat & Adolescent Med, Fac Med, Beirut, Lebanon. RP Nabulsi, M (reprint author), Amer Univ Beirut, Dept Pediat & Adolescent Med, Fac Med, Beirut, Lebanon. EM bnazha@nshs.edu; mn04@aub.edu.lb NR 16 TC 0 Z9 0 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 12 PY 2015 VL 10 IS 3 AR e0119375 DI 10.1371/journal.pone.0119375 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CD7ND UT WOS:000351276300025 PM 25764441 ER PT J AU Ebina, W Rossi, DJ AF Ebina, Wataru Rossi, Derrick J. TI Transcription factor-mediated reprogramming toward hematopoietic stem cells SO EMBO JOURNAL LA English DT Review DE cell fate conversion; hematopoietic stem cells; induced reprogramming; transcription factors ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; ADULT-MOUSE HEMATOPOIESIS; GROUND-STATE PLURIPOTENCY; REGULATES SELF-RENEWAL; MODIFIED MESSENGER-RNA; HUMAN FIBROBLASTS; PROGENITOR CELLS; DEFINED FACTORS; IN-VIVO AB De novo generation of human hematopoietic stem cells (HSCs) from renewable cell types has been a long sought-after but elusive goal in regenerative medicine. Paralleling efforts to guide pluripotent stem cell differentiation by manipulating developmental cues, substantial progress has been made recently toward HSC generation via combinatorial transcription factor (TF)-mediated fate conversion, a paradigm established by Yamanaka's induction of pluripotency in somatic cells by mere four TFs. This review will integrate the recently reported strategies to directly convert a variety of starting cell types toward HSCs in the context of hematopoietic transcriptional regulation and discuss how these findings could be further developed toward the ultimate generation of therapeutic human HSCs. C1 [Ebina, Wataru; Rossi, Derrick J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Ebina, Wataru; Rossi, Derrick J.] Boston Childrens Hosp, Div Hematol Oncol, Program Cellular & Mol Med, Boston, MA USA. [Rossi, Derrick J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Rossi, Derrick J.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Rossi, DJ (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM Derrick.Rossi@childrens.harvard.edu NR 215 TC 12 Z9 12 U1 5 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD MAR 12 PY 2015 VL 34 IS 6 BP 694 EP 709 DI 10.15252/embj.201490804 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CD2BE UT WOS:000350877800003 PM 25712209 ER PT J AU Org, T Duan, D Ferrari, R Montel-Hagen, A Van Handel, B Kerenyi, MA Sasidharan, R Rubbi, L Fujiwara, Y Pellegrini, M Orkin, SH Kurdistani, SK Mikkola, HKA AF Org, Tonis Duan, Dan Ferrari, Roberto Montel-Hagen, Amelie Van Handel, Ben Kerenyi, Marc A. Sasidharan, Rajkumar Rubbi, Liudmilla Fujiwara, Yuko Pellegrini, Matteo Orkin, Stuart H. Kurdistani, Siavash K. Mikkola, Hanna K. A. TI Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence SO EMBO JOURNAL LA English DT Article DE cardiac specification; enhancer; hematopoiesis; mesoderm diversification; transcriptional regulation ID STEM-CELL DIFFERENTIATION; TRANSCRIPTION FACTORS; AORTIC ENDOTHELIUM; GENE-EXPRESSION; MOUSE EMBRYO; HEMOGENIC ENDOTHELIUM; TAL1 FUNCTION; YOLK-SAC; RNA-SEQ; GENOME AB Scl/Tal1 confers hemogenic competence and prevents ectopic cardiomyogenesis in embryonic endothelium by unknown mechanisms. We discovered that Scl binds to hematopoietic and cardiac enhancers that become epigenetically primed in multipotent cardiovascular mesoderm, to regulate the divergence of hematopoietic and cardiac lineages. Scl does not act as a pioneer factor but rather exploits a pre-established epigenetic landscape. As the blood lineage emerges, Scl binding and active epigenetic modifications are sustained in hematopoietic enhancers, whereas cardiac enhancers are decommissioned by removal of active epigenetic marks. Our data suggest that, rather than recruiting corepressors to enhancers, Scl prevents ectopic cardiogenesis by occupying enhancers that cardiac factors, such as Gata4 and Hand1, use for gene activation. Although hematopoietic Gata factors bind with Scl to both activated and repressed genes, they are dispensable for cardiac repression, but necessary for activating genes that enable hematopoietic stem/progenitor cell development. These results suggest that a unique subset of enhancers in lineage-specific genes that are accessible for regulators of opposing fates during the time of the fate decision provide a platform where the divergence of mutually exclusive fates is orchestrated. C1 [Org, Tonis; Duan, Dan; Montel-Hagen, Amelie; Van Handel, Ben; Sasidharan, Rajkumar; Rubbi, Liudmilla; Pellegrini, Matteo; Mikkola, Hanna K. A.] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. [Ferrari, Roberto; Kurdistani, Siavash K.] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90024 USA. [Ferrari, Roberto; Kurdistani, Siavash K.; Mikkola, Hanna K. A.] Univ Calif Los Angeles, Eli & Edythe Broad Stem Cell Res Ctr, Los Angeles, CA USA. [Kerenyi, Marc A.; Fujiwara, Yuko; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Kerenyi, Marc A.; Fujiwara, Yuko; Orkin, Stuart H.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Div Hematol Oncol,Childrens Hosp Boston,Harvard S, Boston, MA 02115 USA. RP Mikkola, HKA (reprint author), Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. EM hmikkola@mcdb.ucla.edu RI Org, Tonis/E-8596-2010; OI Org, Tonis/0000-0003-3071-2183; Kurdistani, Siavash/0000-0003-3295-3511 FU California Institute for Regenerative Medicine (CIRM) New Faculty Award [RN1-00557]; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA Research Award; American Heart Association [14GRNT20480340]; Leukemia Lymphoma Society Scholar Award [20103778]; Leukemia Lymphoma Society postdoctoral fellowship [57537-13]; European Union through the European Social Fund [MJD284]; government of P.R.C through the State Scholarship Fund [2011624028]; HFSP; American Society of Hematology; NIH/NHLBI [T32 HL69766]; [P30DK049216] FX The authors thank the Broad Stem Cell Research Center (BSCRC) Flow Cytometry Core for FACS sorting and BSCRC Sequencing core for next-generation sequencing. This work was funded by the California Institute for Regenerative Medicine (CIRM) New Faculty Award (RN1-00557), the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA Research Award, American Heart Association (#14GRNT20480340), and Leukemia Lymphoma Society Scholar Award to HKAM (20103778). TO was supported by Leukemia Lymphoma Society postdoctoral fellowship (57537-13) and by the European Union through the European Social Fund (Mobilitas Grant No. MJD284). DD was supported by the government of P.R.C through the State Scholarship Fund (File No. 2011624028). AMH was supported by a fellowship from HFSP and American Society of Hematology. BVH was supported by the NIH/NHLBI T32 HL69766. Contributions of YF and SHO were supported by P30DK049216. NR 89 TC 15 Z9 15 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD MAR 12 PY 2015 VL 34 IS 6 BP 759 EP 777 DI 10.15252/embj.201490542 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CD2BE UT WOS:000350877800007 PM 25564442 ER PT J AU Genovese, G Jaiswal, S Ebert, BL McCarroll, SA AF Genovese, Giulio Jaiswal, Siddhartha Ebert, Benjamin L. McCarroll, Steven A. TI Clonal Hematopoiesis and Blood-Cancer Risk REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Genovese, Giulio] Broad Inst, Cambridge, MA 02142 USA. [Jaiswal, Siddhartha] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ebert, Benjamin L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [McCarroll, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. RP Genovese, G (reprint author), Broad Inst, Cambridge, MA 02142 USA. EM mccarroll@genetics.med.harvard.edu NR 4 TC 10 Z9 10 U1 2 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 12 PY 2015 VL 372 IS 11 BP 1071 EP 1072 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CD0XK UT WOS:000350797300015 PM 25760361 ER PT J AU Nunez, JK Lee, ASY Engelman, A Doudna, JA AF Nunez, James K. Lee, Amy S. Y. Engelman, Alan Doudna, Jennifer A. TI Integrase-mediated spacer acquisition during CRISPR-Cas adaptive immunity SO NATURE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SHORT PALINDROMIC REPEATS; TOPOISOMERASE-I MUTANTS; DNA STRAND TRANSFER; ESCHERICHIA-COLI; ACQUIRED-RESISTANCE; BACTERIAL IMMUNITY; GYRASE GENES; SEQUENCE; SYSTEM AB Bacteria and archaea insert spacer sequences acquired from foreign DNAs into CRISPR loci to generate immunological memory. The Escherichia coli Cas1-Cas2 complex mediates spacer acquisition in vivo, but the molecular mechanism of this process is unknown. Here we show that the purified Cas1-Cas2 complex integrates oligonucleotide DNA substrates into acceptor DNA to yield products similar to those generated by retroviral integrases and transposases. Cas1 is the catalytic subunit and Cas2 substantially increases integration activity. Protospacer DNA with free 3'-OH ends and supercoiled target DNA are required, and integration occurs preferentially at the ends of CRISPR repeats and at sequences adjacent to cruciform structures abutting AT-rich regions, similar to the CRISPR leader sequence. Our results demonstrate the Cas1-Cas2 complex to be the minimal machinery that catalyses spacer DNA acquisition and explain the significance of CRISPR repeats in providing sequence and structural specificity for Cas1-Cas2-mediated adaptive immunity. C1 [Nunez, James K.; Lee, Amy S. Y.; Doudna, Jennifer A.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Lee, Amy S. Y.; Doudna, Jennifer A.] Univ Calif Berkeley, Ctr RNA Syst Biol, Berkeley, CA 94720 USA. [Engelman, Alan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Engelman, Alan] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Doudna, Jennifer A.] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA. [Doudna, Jennifer A.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. [Doudna, Jennifer A.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA. RP Doudna, JA (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA. EM doudna@berkeley.edu FU US National Science Foundation [1244557]; NIH [AI070042]; NIH S10 Instrumentation Grants [S10RR029668, S10RR027303]; US National Science Foundation Graduate Research Fellowship; UC Berkeley Chancellor's Graduate Fellowship; American Cancer Society [PF-14-108-01-RMC] FX We are grateful to M. Chung, P. J. Kranzusch and A.V. Wright for technical assistance and members of the Doudna laboratory and J. Cate for discussions. This project was funded by US National Science Foundation grant no. 1244557 to J.A.D. and by NIH grant AI070042 to A.E. This work used the Vincent J. Coates Genomics Sequencing Laboratory at UC Berkeley, supported by NIH S10 Instrumentation Grants S10RR029668 and S10RR027303. J.K.N. is supported by a US National Science Foundation Graduate Research Fellowship and a UC Berkeley Chancellor's Graduate Fellowship. A.S.Y.L. is supported as an American Cancer Society Postdoctoral Fellow (PF-14-108-01-RMC). J.A.D. is an Investigator of the Howard Hughes Medical Institute and a member of the Center for RNA Systems Biology. NR 49 TC 66 Z9 69 U1 8 U2 68 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 MAR 12 PY 2015 VL 519 IS 7542 BP 193 EP + DI 10.1038/nature14237 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CD0NH UT WOS:000350770500030 PM 25707795 ER PT J AU Zhu, W Dotson, AL Libal, NL Lapato, AS Bodhankar, S Offner, H Alkayed, NJ AF Zhu, W. Dotson, A. L. Libal, N. L. Lapato, A. S. Bodhankar, S. Offner, H. Alkayed, N. J. TI RECOMBINANT T-CELL RECEPTOR LIGAND RTL1000 LIMITS INFLAMMATION AND DECREASES INFARCT SIZE AFTER EXPERIMENTAL ISCHEMIC STROKE IN MIDDLE-AGED MICE SO NEUROSCIENCE LA English DT Article DE ischemic stroke; immunotherapy; recombinant T-cell receptor ligand; HLA-DR2 transgenic mice ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; RECOMMENDATIONS; LYMPHOCYTES AB We have previously demonstrated that recombinant T-cell receptor ligand 1000 (RTL1000) reduces infarct size and improves long-term functional recovery after experimental stroke in young transgenic mice expressing human leukocyte antigen DR2 (DR2-Tg). In this study, we determined the effect of RTL1000 on infarct size in 12-month-old middle-aged DR2-Tg mice, and investigated its mechanism of action. Twelve-month-old male DR2-Tg mice underwent 60 min of intraluminal reversible middle cerebral artery occlusion (MCAO). Vehicle or RTL1000 was injected 4, 24, 48 and 72 h after MCAO. Cortical, striatal and total hemispheric infarcts were measured 96 h after stroke. Spleen and brain tissues were collected 96 h after stroke for immunological analysis. Our data showed that RTL1000 significantly reduced infarct size 96 h after MCAO in middle-aged male DR2-Tg mice. RTL1000 decreased the number of activated monocytes/microglia cells (CD11b(+)CD45(hi)) and CD3(+) T cells in the ischemic hemisphere. RTL1000 also reduced the percentage of total T cells and inflammatory neutrophils in the spleen. These findings suggest that RTL1000 protects against ischemic stroke in middle-aged male mice by limiting post-ischemic inflammation. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Zhu, W.; Libal, N. L.; Offner, H.; Alkayed, N. J.] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. [Alkayed, N. J.] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97239 USA. [Dotson, A. L.; Lapato, A. S.; Bodhankar, S.; Offner, H.; Alkayed, N. J.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Dotson, A. L.; Lapato, A. S.; Bodhankar, S.; Offner, H.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Alkayed, NJ (reprint author), Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. EM alkayedn@ohsu.edu OI Lapato, Andrew/0000-0002-4931-7370 FU NIH [NS076013 (STTR)]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development FX This work was supported by NIH Grants #NS076013 (STTR) and by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. NR 30 TC 2 Z9 2 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD MAR 12 PY 2015 VL 288 BP 112 EP 119 DI 10.1016/j.neuroscience.2014.12.037 PG 8 WC Neurosciences SC Neurosciences & Neurology GA CA2TD UT WOS:000348759600011 PM 25556831 ER PT J AU Slama, MCC Delgutte, B AF Slama, Michael C. C. Delgutte, Bertrand TI Neural Coding of Sound Envelope in Reverberant Environments SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amplitude modulation; envelope; inferior colliculus; reverberation; single-unit; unanesthetized rabbit ID AMPLITUDE-MODULATED TONES; VENTRAL COCHLEAR NUCLEUS; SUPERIOR OLIVARY COMPLEX; AUDITORY-NERVE FIBERS; SMALL-ROOM ACOUSTICS; INFERIOR COLLICULUS; SPEECH-INTELLIGIBILITY; INTERAURAL CORRELATION; UNANESTHETIZED RABBIT; LATERAL LEMNISCUS AB Speech reception depends critically on temporal modulations in the amplitude envelope of the speech signal. Reverberation encountered in everyday environments can substantially attenuate these modulations. To assess the effect of reverberation on the neural coding of amplitude envelope, we recorded from single units in the inferior colliculus (IC) of unanesthetized rabbit using sinusoidally amplitude modulated (AM) broadband noise stimuli presented in simulated anechoic and reverberant environments. Although reverberation degraded both rate and temporal coding of AM in IC neurons, in most neurons, the degradation in temporal coding was smaller than the AM attenuation in the stimulus. This compensation could largely be accounted for by the compressive shape of the modulation input-output function (MIOF), which describes the nonlinear transformation of modulation depth from acoustic stimuli into neural responses. Additionally, in a subset of neurons, the temporal coding of AM was better for reverberant stimuli than for anechoic stimuli having the same modulation depth at the ear. Using hybrid anechoic stimuli that selectively possess certain properties of reverberant sounds, we show that this reverberant advantage is not caused by envelope distortion, static interaural decorrelation, or spectral coloration. Overall, our results suggest that the auditory system may possess dual mechanisms that make the coding of amplitude envelope relatively robust in reverberation: one general mechanism operating for all stimuli with small modulation depths, and another mechanism dependent on very specific properties of reverberant stimuli, possibly the periodic fluctuations in interaural correlation at the modulation frequency. C1 [Slama, Michael C. C.; Delgutte, Bertrand] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. [Delgutte, Bertrand] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Slama, Michael C. C.; Delgutte, Bertrand] MIT, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. RP Delgutte, B (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. EM Bertrand_Delgutte@meei.harvard.edu OI , /0000-0003-1349-9608 FU National Institutes of Health [R01 DC002258, P30 DC0005209]; Paul and Daisy Soros Fellowship for New Americans FX This work was supported by National Institutes of Health Grants R01 DC002258 and P30 DC0005209, and the Paul and Daisy Soros Fellowship for New Americans. We thank Sasha Devore, Ken Hancock, Melissa McKinnon, Chris Scarpino, Ishmael Stefanov-Wagner, Shig Kuwada, and Rachel Slama for technical assistance, and Barbara Shinn-Cunningham, Michale Fee, and Luke Shaheen for valuable comments on the manuscript. NR 71 TC 4 Z9 4 U1 1 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 11 PY 2015 VL 35 IS 10 BP 4452 EP 4468 DI 10.1523/JNEUROSCI.3615-14.2015 PG 17 WC Neurosciences SC Neurosciences & Neurology GA CE9YP UT WOS:000352199900029 PM 25762687 ER PT J AU Howie, LJ Peppercorn, JM AF Howie, Lynn J. Peppercorn, Jeffrey M. TI Polls and Policy: Signals or Substance SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CANCER CARE; UNITED-STATES; MEDICARE; COST; EXPERIENCE; ATTITUDES; VIEWS C1 [Howie, Lynn J.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Peppercorn, Jeffrey M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Howie, LJ (reprint author), Duke Univ, Med Ctr, Durham, NC 27710 USA. NR 17 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 10 PY 2015 VL 33 IS 8 BP 819 EP + DI 10.1200/JCO.2014.59.8524 PG 4 WC Oncology SC Oncology GA CK2QI UT WOS:000356055600005 PM 25624434 ER PT J AU Overmoyer, B AF Overmoyer, Beth TI Treatment With Adjuvant Endocrine Therapy for Early-Stage Breast Cancer: Is It Forever? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; ESTROGEN-RECEPTOR; DISTANT RECURRENCE; GENE-EXPRESSION; POSTMENOPAUSAL WOMEN; TAMOXIFEN THERAPY; LYMPH-NODES; PAM50 RISK; FOLLOW-UP; LETROZOLE AB A 64-year-old healthy postmenopausal woman with an intact uterus had been diagnosed with mammo-graphically detected invasive ductal carcinoma of the right breast at the age of 59 years. She underwent breast-conservation surgery, with an excisional biopsy and sentinel lymph node sampling revealing a 1.2-cm Bloom-Richardson grade 2 invasive ductal carcinoma with negative surgical margins and one negative sentinel lymph node. Immunohistochemical testing showed that the tumor was estrogen receptor positive (strong intensity, > 95%) and progesterone receptor positive (strong intensity, 90%) but negative for human epidermal growth factor receptor 2 overexpression. The Oncotype DX(Genomic Health, Redwood City, CA) recurrence score was 13, associated with a 10-year risk of distant recurrence equaling 8% with 5 years of tamoxifen adjuvant treatment. On the basis of this result, she declined chemotherapy and received hypofractionated whole-breast irradiation in 16 fractions without a boost, receiving 42.5 Gy of radiation to the breast. At the time of her diagnosis, baseline bone density demonstrated osteopenia, with a T-score average of -1.5 for the lumbar spine and a T-score average of -1.9 for the left hip. The patient was concerned about the risk of osteoporosis associated with aromatase inhibitors and therefore chose to receive tamoxifen alone as adjuvant endocrine therapy. Serial bone-mineral density evaluation over the subsequent years has shown stable T scores (lumbar spine, -1.3; hip, -1.7). She has tolerated tamoxifen well for 5 years, without experiencing menopausal symptoms or vaginal bleeding. She is requesting an opinion on whether she should receive extended endocrine therapy for an additional 5 years. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Overmoyer, B (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. FU Genentech FX Research Funding: Genentech NR 38 TC 3 Z9 3 U1 0 U2 4 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 MAR 10 PY 2015 VL 33 IS 8 BP 823 EP + DI 10.1200/JCO.2014.58.2361 PG 7 WC Oncology SC Oncology GA CK2QI UT WOS:000356055600007 PM 25624431 ER PT J AU Ezoe, Y Anada, T Yamazaki, H Handa, T Kobayashi, K Takahashi, T Suzuki, O AF Ezoe, Yushi Anada, Takahisa Yamazaki, Hajime Handa, Takuto Kobayashi, Kazuhito Takahashi, Tetsu Suzuki, Osamu TI Characterization of partially hydrolyzed OCP crystals deposited in a gelatin matrix as a scaffold for bone tissue engineering SO JOURNAL OF NANOPARTICLE RESEARCH LA English DT Article DE Octacalcium phosphate; Gelatin; Hydrolysis; Hydroxyapatite; Osteoblasts; Tissue engineering; Nano-biochemistry ID OCTACALCIUM PHOSPHATE; CALCIUM PHOSPHATES; HYDROXYAPATITE; REGENERATION; AMELOGENINS; ADSORPTION; COMPOSITE; CHEMISTRY; SIZE AB The present study was designed to investigate how hydrolysis of octacalcium phosphate (OCP) into hydroxyapatite is affected by the presence of gelatin (Gel) molecules and how osteoblastic cells respond to the resultant OCP hydrolyzate/Gel composites as the hydrolysis advances. OCP was prepared from a solution containing calcium and phosphate ions and Gel molecules, having a composition to produce a 40 wt% OCP as a final co-precipitate as the OCP/Gel. The precipitate was further incubated up to 40 h to advance the hydrolysis of OCP. These precipitates were processed to mold OCP/Gel sponges through lyophilization and dehydrothermal treatment. Chemical analysis, X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, and selected area electron diffraction revealed that the hydrolysis of OCP/Gel composite in hot water advanced in a time-dependent manner and faster than hydrolysis of OCP alone. The effect of Gel on the OCP hydrolysis was further examined in the presence of distinct concentrations of Gel molecules in hot water, showing that the Gel enhanced the hydrolysis as the concentration increased. Proliferation and differentiation of mouse bone marrow stromal ST-2 cells on the hydrolyzed OCP/Gel composites were compatible with Gel sponge alone after 21 days of culture, suggesting that these composites could be a candidate as a scaffold in bone tissue engineering. C1 [Ezoe, Yushi; Handa, Takuto; Kobayashi, Kazuhito; Takahashi, Tetsu] Tohoku Univ, Grad Sch Dent, Div Oral & Maxillofacial Surg, Aoba Ku, Sendai, Miyagi 9808575, Japan. [Ezoe, Yushi; Anada, Takahisa; Handa, Takuto; Kobayashi, Kazuhito; Suzuki, Osamu] Tohoku Univ, Grad Sch Dent, Div Craniofacial Funct Engn, Aoba Ku, Sendai, Miyagi 9808575, Japan. [Yamazaki, Hajime] Forsyth Inst, Dept Appl Oral Sci, Ctr Biomineralizat, Cambridge, MA 02142 USA. [Handa, Takuto] Yokushukai Dent Clin, Yachichuo, Yamagata 9993512, Japan. RP Suzuki, O (reprint author), Tohoku Univ, Grad Sch Dent, Div Craniofacial Funct Engn, Aoba Ku, 4-1 Seiryo Machi, Sendai, Miyagi 9808575, Japan. EM suzuki-o@m.tohoku.ac.jp FU Ministry of Education, Science, Sports, and Culture of Japan [23106010, 25670829, 26670846, 26282133, 26293417] FX This study was supported in part by Grants-in-aid (23106010, 25670829, 26670846, 26282133 and 26293417) from the Ministry of Education, Science, Sports, and Culture of Japan. NR 33 TC 2 Z9 2 U1 2 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1388-0764 EI 1572-896X J9 J NANOPART RES JI J. Nanopart. Res. PD MAR 10 PY 2015 VL 17 IS 3 AR 127 DI 10.1007/s11051-015-2864-1 PG 10 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA CI8IU UT WOS:000355016800003 ER PT J AU Du, ZM Abedalthagafi, M Aizer, AA McHenry, AR Sun, HH Bray, MA Viramontes, O Machaidze, R Brastianos, PK Reardon, DA Dunn, IF Freeman, GJ Ligon, KL Carpenter, AE Alexander, BM Agar, NY Rodig, SJ Bradshaw, EM Santagata, S AF Du, Ziming Abedalthagafi, Malak Aizer, Ayal A. McHenry, Allison R. Sun, Heather H. Bray, Mark-Anthony Viramontes, Omar Machaidze, Revaz Brastianos, Priscilla K. Reardon, David A. Dunn, Ian F. Freeman, Gordon J. Ligon, Keith L. Carpenter, Anne E. Alexander, Brian M. Agar, Nathalie Y. Rodig, Scott J. Bradshaw, Elizabeth M. Santagata, Sandro TI Increased expression of the immune modulatory molecule PD-L1 (CD274) in anaplastic meningioma SO ONCOTARGET LA English DT Article DE meningioma; PD-L1; RNAscope; immunotherapy ID MALIGNANT MENINGIOMAS; SPORADIC MENINGIOMAS; CANCER-IMMUNOTHERAPY; BRAIN-TUMORS; NF2 GENE; MUTATIONS; BLOCKADE; MELANOMA; SAFETY; PROGRESSION AB There are no effective medical treatments for WHO grade III (anaplastic) meningioma. Patients with this high-grade malignancy have a median survival of less than two years. Therapeutics that modulate the mechanisms that inhibit local immune responses in the tumor microenvironment are showing significant and durable clinical responses in patients with treatment refractory high-grade tumors. We examined the immune infiltrate of 291 meningiomas including WHO grade I-III meningiomas using immunohistochemistry and we examined the expression of PD-L1 mRNA by RNAscope in situ hybridization and PD-L1 protein by immunohistochemistry. In meningioma, the tumor infiltrating lymphocytes are predominantly T cells. In anaplastic meningioma, there is a sharp decrease in the number of T cells, including the numbers of CD4+ and CD8+ T cells and cells expressing PD-1 and there is also an increase in the number of FOXP3 expressing immunoregulatory (Treg) cells. PD-L1 expression is increased in anaplastic meningioma - both mRNA and protein. Using patient derived meningioma cell, we confirm that PD-L1 is expressed in meningioma cells themselves, and not solely in infiltrating immune cells. This work indicates that high-grade meningioma harbor an immunosuppressive tumor microenviroment and that increased Treg cells and elevated PD-L1 may contribute to the aggressive phenotype of these tumors. C1 [Du, Ziming; Abedalthagafi, Malak; Sun, Heather H.; Machaidze, Revaz; Ligon, Keith L.; Rodig, Scott J.; Santagata, Sandro] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Du, Ziming; Abedalthagafi, Malak; Aizer, Ayal A.; McHenry, Allison R.; Sun, Heather H.; Viramontes, Omar; Machaidze, Revaz; Brastianos, Priscilla K.; Reardon, David A.; Dunn, Ian F.; Freeman, Gordon J.; Ligon, Keith L.; Alexander, Brian M.; Agar, Nathalie Y.; Rodig, Scott J.; Bradshaw, Elizabeth M.; Santagata, Sandro] Harvard Univ, Sch Med, Boston, MA USA. [Aizer, Ayal A.; Alexander, Brian M.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [McHenry, Allison R.; Bradshaw, Elizabeth M.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Bray, Mark-Anthony; Carpenter, Anne E.] Broad Inst MIT & Harvard, Imaging Platform, Cambridge, MA USA. [Viramontes, Omar; Machaidze, Revaz; Dunn, Ian F.; Agar, Nathalie Y.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Brastianos, Priscilla K.; Reardon, David A.; Freeman, Gordon J.; Ligon, Keith L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Brastianos, Priscilla K.] Massachusetts Gen Hosp, Dept Neurooncol, Boston, MA 02114 USA. [Santagata, Sandro] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Santagata, S (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM ssantagata@partners.org FU National Institutes of Health [RO1 GM089652]; Center for Immune Oncology at the Dana Farber Cancer Institute; Brain Science Foundation; Jared Branfman Sunflowers for Life Fund for Pediatric Brain and Spinal Cancer Research; V Foundation; King Abdulaziz City for Science and Technology (KACST), Saudi Arabia FX The authors would like to thank members of the Santagata, Bradshaw and Agar labs for helpful discussions. The authors would like to thank Chungdak Namgyal for TMA construction and Terri Woo, Teri Bowman and the BWH/DFCI Specialized Histopathology Core for assistance with some of the immunohistochemistry staining. We thank Yuko G. Miki for guidance with cell culturing. We thank Dr. Mariano Viapiano and the Cooperative Human Tissue Network for tissue distributions for generating certain cell lines. We thank William G. Richards, Kristen K. Gill and the BWH tissue bank for access to frozen tissue samples as well as the BWH Division of Neuropathology under the leadership of Dr. Rebecca Folkerth for sample procurement. M.A.B. and A.E.C. were funded by National Institutes of Health RO1 GM089652 and H.H.S. and S.J.R. were supported by the Center for Immune Oncology at the Dana Farber Cancer Institute. This study was supported by Brain Science Foundation (S.S), the Jared Branfman Sunflowers for Life Fund for Pediatric Brain and Spinal Cancer Research (S.S), the V Foundation (S.S), King Abdulaziz City for Science and Technology (KACST), Saudi Arabia (M.A.) and National Institutes of Health RO1 GM089652 (A,E,C). NR 48 TC 19 Z9 20 U1 0 U2 3 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD MAR 10 PY 2015 VL 6 IS 7 BP 4704 EP 4716 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CF8FR UT WOS:000352792000013 PM 25609200 ER PT J AU Golestanirad, L Das, S Schweizer, TA Graham, SJ AF Golestanirad, Laleh Das, Sunit Schweizer, Tom A. Graham, Simon J. TI A preliminary fMRI study of a novel self-paced written fluency task: observation of left-hemispheric activation, and increased frontal activation in late vs. early task phases SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE fMRI; language; verbal fluency; phonemic fluency; tablet; writing ID OVERT VERBAL FLUENCY; EVENT-RELATED FMRI; SEMANTIC FLUENCY; FUNCTIONAL MRI; LANGUAGE DOMINANCE; LESION LOCALIZATION; BRAIN ACTIVATION; PRECENTRAL GYRUS; WORD GENERATION; NORMATIVE DATA AB Neuropsychological tests of verbal fluency are very widely used to characterize impaired cognitive function. For clinical neuroscience studies and potential medical applications, measuring the brain activity that underlies such tests with functional magnetic resonance imaging (fMRI) is of significant interest-but a challenging proposition because overt speech can cause signal artifacts, which tend to worsen as the duration of speech tasks becomes longer. In a novel approach, we present the group brain activity of 12 subjects who performed a self-paced written version of phonemic fluency using fM RI-compatible tablet technology that recorded responses and provided task-related feedback on a projection screen display, over long-duration task blocks (60s). As predicted, we observed robust activation in the left anterior inferior and medial frontal gyri, consistent with previously reported results of verbal fluency tasks which established the role of these areas in strategic word retrieval. In addition, the number of words produced in the late phase (last 30s) of written phonemic fluency was significantly less (p < 0.05) than the number produced in the early phase (first 30s). Activation during the late phase vs. the early phase was also assessed from the first 20s and last 20s of task performance, which eliminated the possibility that the sluggish hemodynamic response from the early phase would affect the activation estimates of the late phase. The last 20s produced greater activation maps covering extended areas in bilateral precuneus, cuneus, middle temporal gyrus, insula, middle frontal gyrus and cingulate gyrus. Among these areas, greater activation was observed in the bilateral middle frontal gyrus (Brodmann area BA 9) and cingulate gyrus (BA 24, 32) likely as part of the initiation, maintenance, and shifting of attentional resources. Consistent with previous pertinent fMRI literature involving overt and covert verbal responses, these findings highlight the promise and practicality of fMRI of written phonemic fluency. C1 [Golestanirad, Laleh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. [Das, Sunit; Schweizer, Tom A.] St Michaels Hosp, Keenan Res Inst, Toronto, ON M5B 1W8, Canada. [Graham, Simon J.] Sunnybrook Hlth Sci Ctr, Sunnybrook Res Inst, Toronto, ON M4N 3M5, Canada. RP Golestanirad, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Biomed Imaging, Bldg 75,Room 2-109,13th St,Third Av, Boston, MA 02129 USA. EM lgolestanirad@mgh.harvard.edu FU Canadian Cancer Society [701770] FX The authors would like to thank Mr. Fred Tam for his assistance in experiment setup and data collection. This research was made possible by a grant awarded by the Canadian Cancer Society, Grant #701770. NR 81 TC 3 Z9 4 U1 4 U2 8 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD MAR 10 PY 2015 VL 9 AR UNSP 113 DI 10.3389/fnhum.2015.00113 PG 14 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA CF3WK UT WOS:000352479500002 PM 25805984 ER PT J AU Barrett, TW Shanmugam, NR Selvam, AP Kazmierczak, SC Prasad, S AF Barrett, Thomas W. Shanmugam, Nandhinee Radha Selvam, Anjan Panneer Kazmierczak, Steven C. Prasad, Shalini TI Novel Nanomonitor ultra-sensitive detection of troponin T SO CLINICA CHIMICA ACTA LA English DT Article DE Point-of-care; Nanotechnology; Troponin T; Functional sensitivity ID CARDIAC TROPONIN; MYOCARDIAL-INFARCTION; ASSAYS; DIAGNOSTICS; POPULATION; PREDICTION; DISEASE AB Background: Troponin is the preferred biomarker for diagnosing myocardial infarction. Point of care devices have not matched the sensitivity of laboratory-based methods for measuring troponin. The Nanomonitor is a novel point-of-care device that uses the change in electrical impedance that occurs when a biomarker binds to its antibody, which is then correlated to the concentration of the target biomarker. Methods: Performance characteristics of the Nanomonitor were evaluated and compared to a standard laboratory-based method. Results: The limit of detection of the Nanomonior for troponin T was 0.0088 ng/l. Total imprecission was 238% and 0.85% at troponin T concentrations of 73 ng/l and 1800 ng/l. The functional sensitivity (10% coeffecient of variation) was 0329 ng/l. The linear regression had a slope of 0.996 (95% confidence interval, 0.991, 1.002), r = 1.00, and an intercept of 15.88 ng/l (95% confidence interval, -68.39 ng/l, 100.15 ng/l). The mean difference between the assays was -7.54 ng/l, determined by Bland-Altman analysis. Conclusion: The Nanomonitor preliminary results have favorable performance characteristics for detecting troponin Tin patient blood, provide results in 15 min, and are portable. More research is needed. (C) 2015 Elsevier B.V. All rights reserved. C1 [Barrett, Thomas W.] Portland VA Med Ctr, Portland, OR USA. [Shanmugam, Nandhinee Radha; Selvam, Anjan Panneer; Prasad, Shalini] Oregon Hlth & Sci Univ, Div Hosp Med, Portland, OR 97201 USA. [Kazmierczak, Steven C.] Univ Texas Dallas, Dept Bioengn, Richardson, TX 75080 USA. Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. RP Prasad, S (reprint author), Univ Texas Dallas, Dept Bioengn, 800 W Campbell Rd,EC 39, Richardson, TX 75080 USA. EM Shalini.Prasad@utdallas.edu RI Radha Shanmugam, Nandhinee/D-1896-2017 OI Radha Shanmugam, Nandhinee/0000-0002-8572-7801 FU National Center for Research Resources (NCRR) [UL1 RR024140] FX This work was presented, in part, in poster form at the Materials Research Society Conference, April 24, 2014, San Francisco, California, "Rapid and Sensitive Detection of Nano-fluidically Trapped Protein Biomarkers". Oregon Nanoscience and Microtechnologies Institute, and Oregon Clinical and Translational Research Institute (OCTRI), grant number UL1 RR024140 from the National Center for Research Resources (NCRR) and the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH), and the Cecil and Ida Green Endowment in Systems Biology at University of Texas at Dallas. NR 25 TC 5 Z9 5 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 EI 1873-3492 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD MAR 10 PY 2015 VL 442 BP 96 EP 101 DI 10.1016/j.cca.2015.01.013 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA CE7TY UT WOS:000352045900019 PM 25619774 ER PT J AU Nowacki, M Nazarewski, L Pokrywczynska, M Kloskowski, T Tyloch, D Pietkun, K Jundzill, A Rasmus, M Warda, K Gagat, M Grzanka, A Bodnar, M Marszalek, A Krawczyk, M Habib, SL Drewa, T AF Nowacki, Maciej Nazarewski, Lukasz Pokrywczynska, Marta Kloskowski, Tomasz Tyloch, Dominik Pietkun, Katarzyna Jundzill, Arkadiusz Rasmus, Marta Warda, Karolina Gagat, Maciej Grzanka, Alina Bodnar, Magdalena Marszalek, Andrzej Krawczyk, Marek Habib, Samy L. Drewa, Tomasz TI Long-Term Influence of Bone Marrow-Derived Mesenchymal Stem Cells on Liver Ischemia-Reperfusion Injury in a Rat Model SO ANNALS OF TRANSPLANTATION LA English DT Article DE Mesenchymal Stromal Cells; Reperfusion Injury; Tissue Engineering ID HEPATIC ISCHEMIA/REPERFUSION INJURY; WARM ISCHEMIA; ANIMAL-MODELS; MURINE MODEL; TRANSPLANTATION; APOPTOSIS; PROTECTS; THERAPY; SURGERY; INNATE AB Background: The aim of this study was to evaluate the long-term usefulness of intraportal injection of the bone marrow-derived mesenchymal stem cells (BM-MSCs) in limitation of experimentally induced ischemia-reperfusion injury (IRI) in a rat model. Material/Methods: Twenty Wistar rats were divided into 3 groups: donor group (n=5), study group (n=10), and control group (n=5). IRI was performed using a modified hanging-weight system after left portal triad occlusion in study group animals. Isolated autologous BM-MSCs were labeled with fluorochrome PKH-26 then intraportally injected into the rats in the study group. Control group animals were intraportally injected with 1 ml of PBS. Follow-up was 3 months, after which animals were sacrificed for histopathological examination. Migration of BM-MSCs into different organs was examined. Results: H&E staining of liver tissue sections from "time zero" biopsies did not show many irregularities in structural or histological construction compared to liver sections from the control group. However, a small amount of centrilobular hepatocyte necrosis and coagulative necrosis with neutrophil infiltration areas was observed in liver sections of the study group. The migration assay of BM-MSCs labeled with PKH-26 showed the highest positive BM-MSCs staining (6%) in the spleen, while few positively stained cells were found (2%) in liver sections. No BM-MSCs were detected in brain, kidney, or lung tissues. Conclusions: These results suggest that intraportal bone marrow-derived mesenchymal stem cell injection is safe and cells do not migrate chaotically to other organs after targeted implementation. C1 [Nowacki, Maciej; Pokrywczynska, Marta; Kloskowski, Tomasz; Tyloch, Dominik; Pietkun, Katarzyna; Jundzill, Arkadiusz; Rasmus, Marta; Warda, Karolina; Drewa, Tomasz] Nicolaus Copernicus Univ Torun, Coll Med Bydgoszcz, Dept Tissue Engn, Chair Regenerat Med, Bydgoszcz, Poland. [Nazarewski, Lukasz; Krawczyk, Marek] Med Univ Warsaw, Dept Gen Transplant & Liver Surg, Warsaw, Poland. [Gagat, Maciej; Grzanka, Alina] Nicolaus Copernicus Univ Torun, Coll Med Bydgoszcz, Dept Histol & Embryol, Bydgoszcz, Poland. [Bodnar, Magdalena; Marszalek, Andrzej] Nicolaus Copernicus Univ Torun, Coll Med Bydgoszcz, Dept Clin Pathomorphol, Bydgoszcz, Poland. [Marszalek, Andrzej] Poznan Univ Med Sci, Dept Oncol Pathol, Poznan, Poland. [Marszalek, Andrzej] Greater Poland Oncol Ctr, Poznan, Poland. [Habib, Samy L.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Habib, Samy L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Drewa, Tomasz] Nicolaus Copernicus Hosp, Dept Gen & Oncol Urol, Torun, Poland. RP Kloskowski, T (reprint author), Nicolaus Copernicus Univ Torun, Coll Med Bydgoszcz, Dept Tissue Engn, Chair Regenerat Med, Bydgoszcz, Poland. EM tomaszkloskowski@op.pl RI Kloskowski, Tomasz/D-4353-2014; Bodnar, Magdalena/D-6131-2014; Gagat, Maciej/D-5356-2014; Grzanka, Alina/D-9941-2014; Pietkun , Katarzyna/Q-6718-2016 OI Kloskowski, Tomasz/0000-0001-5599-9315; Bodnar, Magdalena/0000-0003-3748-1058; Gagat, Maciej/0000-0002-5445-8821; FU Nicolaus Copernicus University [112, 266] FX This work was supported by research task within framework of the statutory activities no. 112 and 266 from Nicolaus Copernicus University NR 47 TC 3 Z9 3 U1 1 U2 5 PU INT SCIENTIFIC LITERATURE, INC PI SMITHTOWN PA 361 FOREST LANE, SMITHTOWN, NY 11787 USA SN 1425-9524 J9 ANN TRANSPL JI Ann. Transpl. PD MAR 10 PY 2015 VL 20 BP 132 EP 140 DI 10.12659/AOT.892364 PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA CE0DV UT WOS:000351475600001 PM 25754665 ER PT J AU Rabinstein, AA Anderson, CD AF Rabinstein, Alejandro A. Anderson, Christopher D. TI Time is brain also counts for ICH SO NEUROLOGY LA English DT Editorial Material ID ACUTE INTRACEREBRAL HEMORRHAGE; HEMATOMA GROWTH; DETERMINANT; OUTCOMES C1 [Rabinstein, Alejandro A.] Mayo Clin, Dept Neurol, Rochester, MN 55902 USA. [Anderson, Christopher D.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Rabinstein, AA (reprint author), Mayo Clin, Dept Neurol, Rochester, MN 55902 USA. EM rabinstein.alejandro@mayo.edu OI Anderson, Christopher/0000-0002-0053-2002 FU NINDS NIH HHS [K23 NS086873-01] 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD MAR 10 PY 2015 VL 84 IS 10 BP 970 EP 971 DI 10.1212/WNL.0000000000001349 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA CD9YR UT WOS:000351458100007 PM 25663224 ER PT J AU Beecham, GW Dickson, DW Scott, WK Martin, ER Schellenberg, G Nuytemans, K Larson, EB Buxbaum, JD Trojanowski, JQ Van Deerlin, VM Hurtig, HI Mash, DC Beach, TG Troncoso, JC Pletnikova, O Frosch, MP Ghetti, B Foroud, TM Honig, LS Marder, K Vonsattel, JP Goldman, SM Vinters, HV Ross, OA Wszolek, ZK Wang, LY Dykxhoorn, DM Pericak-Vance, MA Montine, TJ Leverenz, JB Dawson, TM Vance, JM AF Beecham, Gary W. Dickson, Dennis W. Scott, William K. Martin, Eden R. Schellenberg, Gerard Nuytemans, Karen Larson, Eric B. Buxbaum, Joseph D. Trojanowski, John Q. Van Deerlin, Vivianna M. Hurtig, Howard I. Mash, Deborah C. Beach, Thomas G. Troncoso, Juan C. Pletnikova, Olga Frosch, Matthew P. Ghetti, Bernardino Foroud, Tatiana M. Honig, Lawrence S. Marder, Karen Vonsattel, Jean Paul Goldman, Samuel M. Vinters, Harry V. Ross, Owen A. Wszolek, Zbigniew K. Wang, Liyong Dykxhoorn, Derek M. Pericak-Vance, Margaret A. Montine, Thomas J. Leverenz, James B. Dawson, Ted M. Vance, Jeffery M. TI PARK10 is a major locus for sporadic neuropathologically confirmed Parkinson disease SO NEUROLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; CLINICAL-DIAGNOSIS; GENETIC-VARIATION; ONSET; IDENTIFICATION; METAANALYSIS; ACCURACY; RISK; PREDICTION; IMPUTATION AB Objective: To minimize pathologic heterogeneity in genetic studies of Parkinson disease (PD), the Autopsy-Confirmed Parkinson Disease Genetics Consortium conducted a genome-wide association study using both patients with neuropathologically confirmed PD and controls. Methods: Four hundred eighty-four cases and 1,145 controls met neuropathologic diagnostic criteria, were genotyped, and then imputed to 3,922,209 variants for genome-wide association study analysis. Results: A small region on chromosome 1 was strongly associated with PD (rs10788972; p = 6.23 x 10(-8)). The association peak lies within and very close to the maximum linkage peaks of 2 prior positive linkage studies defining the PARK10 locus. We demonstrate that rs10788972 is in strong linkage disequilibrium with rs914722, the single nucleotide polymorphism defining the PARK10 haplotype previously shown to be significantly associated with age at onset in PD. The region containing the PARK10 locus was significantly reduced from 10.6 megabases to 100 kilobases and contains 4 known genes: TCEANC2, TMEM59, miR-4781, and LDLRAD1. Conclusions: We confirm the association of a PARK10 haplotype with the risk of developing idiopathic PD. Furthermore, we significantly reduce the size of the PARK10 region. None of the candidate genes in the new PARK10 region have been previously implicated in the biology of PD, suggesting new areas of potential research. This study strongly suggests that reducing pathologic heterogeneity may enhance the application of genetic association studies to PD. C1 [Beecham, Gary W.; Scott, William K.; Martin, Eden R.; Nuytemans, Karen; Wang, Liyong; Dykxhoorn, Derek M.; Pericak-Vance, Margaret A.; Vance, Jeffery M.] Miami Univ, Miller Sch Med, John P Hussman Inst Human Genom, Oxford, OH 45056 USA. [Mash, Deborah C.] Miami Univ, Miller Sch Med, Univ Miami Brain Endowment Bank, Oxford, OH 45056 USA. [Dickson, Dennis W.; Ross, Owen A.] Mayo Clin Florida, Dept Neurosci, Jacksonville, FL USA. [Wszolek, Zbigniew K.] Mayo Clin Florida, Dept Neurol, Jacksonville, FL USA. [Schellenberg, Gerard; Trojanowski, John Q.; Van Deerlin, Vivianna M.; Hurtig, Howard I.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA USA. [Larson, Eric B.] Grp Hlth Res Inst, Seattle, WA USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Beach, Thomas G.] Arizona Alzheimers Consortium, Phoenix, AZ USA. [Beach, Thomas G.] Sun Hlth Res Inst, Sun City, AZ USA. [Troncoso, Juan C.; Pletnikova, Olga] Johns Hopkins Univ, Sch Med, Dept Pathol, Div Neuropathol, Baltimore, MD 21205 USA. [Dawson, Ted M.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Dawson, Ted M.] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, Kubik Lab Neuropathol, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. [Ghetti, Bernardino] Indiana Univ Sch Med, Indiana Alzheimer Dis Ctr, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA. [Foroud, Tatiana M.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Honig, Lawrence S.; Marder, Karen] Columbia Univ, Gertrude H Sergievsky Ctr, Dept Neurol, New York, NY 10027 USA. [Marder, Karen] Columbia Univ, Gertrude H Sergievsky Ctr, Dept Psychiat, New York, NY 10027 USA. Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA. [Vonsattel, Jean Paul] Taub Inst Res Alzheimers Dis & Aging Brain, Dept Pathol & Cell Biol, New York, NY USA. [Goldman, Samuel M.] Parkinsons Inst, Sunnyvale, CA USA. [Vinters, Harry V.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med Neuropathol, Los Angeles, CA 90024 USA. [Vinters, Harry V.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. [Montine, Thomas J.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Seattle, WA USA. [Leverenz, James B.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Vance, JM (reprint author), Miami Univ, Miller Sch Med, John P Hussman Inst Human Genom, Oxford, OH 45056 USA. EM jvance@med.miami.edu OI Buxbaum, Joseph/0000-0001-8898-8313 FU NIH; JPB Foundation; NIH, National Institute on Aging (NIH-NIA) [ADGC U01 AG032984, RC2 AG036528, NACC U01 AG016976, NCRAD U24 AG021886, NIA LOAD U24 AG026395, U24 AG026390]; Banner Sun Health Research Institute [P30 AG019610]; Boston University [P30 AG013846, U01 AG10483, R01 CA129769, R01 MH080295, R01 AG017173, R01 AG025259, R01AG33193]; Columbia University [P01 AG007232, P50 AG008702, R37 AG015473]; Duke University [P30 AG028377, AG05128]; Emory University [AG025688]; Group Health Research Institute [UO1 AG06781, UO1 HG004610]; Indiana University [P30 AG10133]; Johns Hopkins University [P50 AG005146, R01 AG020688]; Massachusetts General Hospital [P50 AG005134]; Mayo Clinic [P50 AG016574]; Mount Sinai School of Medicine [P50 AG005138, P01 AG002219]; New York University [P30 AG08051, MO1RR00096, UL1 RR029893, 5R01AG012101, 5R01AG022374, 5R01AG013616, 1RC2AG036502, 1R01AG035137]; Northwestern University [P30 AG013854]; Oregon Health & Science University [P30 AG008017, R01 AG026916]; Rush University [P30 AG010161, R01 AG019085, R01 AG15819, R01 AG17917, R01 AG30146]; TGen [R01 NS059873]; University of Alabama at Birmingham [P50 AG016582, UL1RR02777]; University of Arizona [R01 AG031581]; University of California, Davis [P30 AG010129]; University of California, Irvine [P50 AG016573, P50 AG016575, P50 AG016576, P50 AG016577]; University of California, Los Angeles [P50 AG016570]; University of California, San Diego [P50 AG005131]; University of California, San Francisco [P50 AG023501, P01 AG019724]; University of Kentucky [P30 AG028383, AG05144]; University of Michigan [P50 AG008671]; University of Pennsylvania [P30 AG010124]; University of Pittsburgh [P50 AG005133, AG030653]; University of Southern California [P50 AG005142]; University of Texas Southwestern [P30 AG012300]; University of Miami [R01 AG027944, AG010491, AG027944, AG021547, AG019757]; University of Washington [P50 AG005136]; Vanderbilt University [R01 AG019085]; Washington University [P50 AG005681, P01 AG03991]; National Institute of Neurological Disorders and Stroke [NS39764]; NIMH [MH60451]; GlaxoSmithKline; Kronos Science; NIA [AG034504]; Banner Alzheimer's Foundation; Alzheimer's Institute; Medical Research Council; state of Arizona; Medical Research Council, NHS trusts; Newcastle University; Higher Education Funding Council for England [HEFCE]; Alzheimer's Research Trust [ART]; BRACE; North Bristol NHS Trust Research and Innovation Department; DeNDRoN; Stichting MS Research; Brain Net Europe; Hersenstichting Nederland Breinbrekend Werk; International Parkinson Fonds; Internationale Stiching Alzheimer Onderzoek; Institut de Neuropatologia; Servei Anatomia Patologica; Universitat de Barcelona; Abbott; AstraZeneca AB; Bayer Schering Pharma AG; Bristol-Myers Squibb; Eisai Global Clinical Development; Elan Corporation; Genentech; GE Healthcare; Innogenetics; Johnson Johnson; Eli Lilly and Co.; Medpace, Inc.; Merck and Co., Inc.; Novartis AG; Pfizer Inc.; F. Hoffmann-La Roche; Schering-Plough; Synarc, Inc.; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Dana Foundation; National Institute of Biomedical Imaging and Bioengineering; NIA grants [U01 AG024904, RC2 AG036535, K01 AG030514]; Alzheimer's Association [IIRG-08-89720, IIRG-0514147]; US Department of Veterans Affairs Administration, Office of Research and Development, Biomedical Laboratory Research Program; Wellcome Trust; Howard Hughes Medical Institute; Canadian Institute of Health Research; [P50 NS072187]; [P50 NS053488]; [U24 NS072026]; [NS38377]; [AG06781]; [AG005136]; [NS062684]; [P50 AG16570]; [R01NS37167]; [P30AG10133]; [U24AG021886]; [P50 NS038372]; [NS039764]; [NS071674] FX Primary funding was by the NIH. A complete description of the Alzheimer Disease Genetics Consortium funding is below. This project was supported by the following: P50 NS072187, P50 AG016574 (D.W.D., O.A.R., Z.K.W.); P50 NS053488 (J.Q.T., V.M.V., H.I.H.); U24 NS072026 (T.G.B.); NS38377 and the JPB Foundation (T.M.D., J.C.T., O.P.); AG06781, AG005136, and NS062684 (T.J.M.); P50 AG16570 (H.V.V.); P01 AG007232 (L.S.H.); AG005136 and NS062684 (J.B.L.); R01NS37167, P30AG10133, and U24AG021886 (T.F., B.G.); P50 AG005134 and P50 NS038372 (M.P.F.); NS039764 and NS071674 (G.W.B., W.K.S., E.R.M., L.W., K.N., D.M.D., J.M.V.). The Alzheimer Disease Genetics Consortium was supported by the NIH, National Institute on Aging (NIH-NIA), which supported this work through the following grants: ADGC, U01 AG032984, RC2 AG036528; NACC, U01 AG016976; NCRAD, U24 AG021886; NIA LOAD, U24 AG026395, U24 AG026390; Banner Sun Health Research Institute, P30 AG019610; Boston University, P30 AG013846, U01 AG10483, R01 CA129769, R01 MH080295, R01 AG017173, R01 AG025259, R01AG33193; Columbia University, P50 AG008702, R37 AG015473, P01 AG007232; Duke University, P30 AG028377, AG05128; Emory University, AG025688; Group Health Research Institute, UO1 AG06781, UO1 HG004610; Indiana University, P30 AG10133; Johns Hopkins University, P50 AG005146, R01 AG020688; Massachusetts General Hospital, P50 AG005134; Mayo Clinic, P50 AG016574; Mount Sinai School of Medicine, P50 AG005138, P01 AG002219; New York University, P30 AG08051, MO1RR00096, UL1 RR029893, 5R01AG012101, 5R01AG022374, 5R01AG013616, 1RC2AG036502, 1R01AG035137; Northwestern University, P30 AG013854; Oregon Health & Science University, P30 AG008017, R01 AG026916; Rush University, P30 AG010161, R01 AG019085, R01 AG15819, R01 AG17917, R01 AG30146; TGen, R01 NS059873; University of Alabama at Birmingham, P50 AG016582, UL1RR02777; University of Arizona, R01 AG031581; University of California, Davis, P30 AG010129; University of California, Irvine, P50 AG016573, P50, P50 AG016575, P50 AG016576, P50 AG016577; University of California, Los Angeles, P50 AG016570; University of California, San Diego, P50 AG005131; University of California, San Francisco, P50 AG023501, P01 AG019724; University of Kentucky, P30 AG028383, AG05144; University of Michigan, P50 AG008671; University of Pennsylvania, P30 AG010124; University of Pittsburgh, P50 AG005133, AG030653; University of Southern California, P50 AG005142; University of Texas Southwestern, P30 AG012300; University of Miami, R01 AG027944, AG010491, AG027944, AG021547, AG019757; University of Washington, P50 AG005136; Vanderbilt University, R01 AG019085; and Washington University, P50 AG005681, P01 AG03991. The Kathleen Price Bryan Brain Bank at Duke University Medical Center is funded by National Institute of Neurological Disorders and Stroke grant NS39764, NIMH MH60451 and by GlaxoSmithKline. Genotyping of the TGEN2 cohort was supported by Kronos Science. The TGen series was also funded by NIA grant AG034504 to A.J.M., The Banner Alzheimer's Foundation, The Johnnie B. Byrd, Sr.; , Alzheimer's Institute, the Medical Research Council, and the state of Arizona and also includes samples from the following sites: Newcastle Brain Tissue Resource (funding via the Medical Research Council, local NHS trusts, and Newcastle University), MRC London Brain Bank for Neurodegenerative Diseases (funding via the Medical Research Council), South West Dementia Brain Bank (funding via numerous sources including the Higher Education Funding Council for England [HEFCE], Alzheimer's Research Trust [ART], BRACE, as well as North Bristol NHS Trust Research and Innovation Department and DeNDRoN), The Netherlands Brain Bank (funding via numerous sources including Stichting MS Research, Brain Net Europe, Hersenstichting Nederland Breinbrekend Werk, International Parkinson Fonds, Internationale Stiching Alzheimer Onderzoek), Institut de Neuropatologia, Servei Anatomia Patologica, Universitat de Barcelona. ADNI funding for ADNI is through the Northern California Institute for Research and Education by grants from Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson & Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc., F. Hoffmann-La Roche, Schering-Plough, Synarc, Inc., Alzheimer's Association, Alzheimer's Drug Discovery Foundation, the Dana Foundation, and by the National Institute of Biomedical Imaging and Bioengineering and NIA grants U01 AG024904, RC2 AG036535, and K01 AG030514. The authors thank Drs. D. Stephen Snyder and Marilyn Miller from NIA who are ex officio ADGC members. Support was also from the Alzheimer's Association (LAF, IIRG-08-89720; MP-V, IIRG-0514147) and the US Department of Veterans Affairs Administration, Office of Research and Development, Biomedical Laboratory Research Program. P.S.G.-H. is supported by Wellcome Trust, Howard Hughes Medical Institute, and the Canadian Institute of Health Research. NR 27 TC 13 Z9 13 U1 0 U2 3 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 MAR 10 PY 2015 VL 84 IS 10 BP 972 EP 980 DI 10.1212/WNL.0000000000001332 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CD9YR UT WOS:000351458100008 PM 25663231 ER PT J AU Ciaranello, AL Myer, L Kelly, K Christensen, S Daskilewicz, K Doherty, K Bekker, LG Hou, T Wood, R Francke, JA Wools-Kaloustian, K Freedberg, KA Walensky, RP AF Ciaranello, Andrea L. Myer, Landon Kelly, Kathleen Christensen, Sarah Daskilewicz, Kristen Doherty, Katie Bekker, Linda-Gail Hou, Taige Wood, Robin Francke, Jordan A. Wools-Kaloustian, Kara Freedberg, Kenneth A. Walensky, Rochelle P. TI Point-of-Care CD4 Testing to Inform Selection of Antiretroviral Medications in South African Antenatal Clinics: A Cost-Effectiveness Analysis SO PLOS ONE LA English DT Article ID TO-CHILD TRANSMISSION; RESOURCE-LIMITED SETTINGS; SINGLE-DOSE NEVIRAPINE; HIV-INFECTED CHILDREN; CAPE-TOWN; RANDOMIZED-TRIAL; PREGNANT-WOMEN; PILOT PROGRAM; COTE-DIVOIRE; THERAPY AB Background Many prevention of mother-to-child HIV transmission (PMTCT) programs currently prioritize antiretroviral therapy (ART) for women with advanced HIV. Point-of-care (POC) CD4 assays may expedite the selection of three-drug ART instead of zidovudine, but are costlier than traditional laboratory assays. Methods We used validated models of HIV infection to simulate pregnant, HIV-infected women (mean age 26 years, gestational age 26 weeks) in a general antenatal clinic in South Africa, and their infants. We examined two strategies for CD4 testing after HIV diagnosis: laboratory (test rate: 96%, result-return rate: 87%, cost: $14) and POC (test rate: 99%, result-return rate: 95%, cost: $26). We modeled South African PMTCT guidelines during the study period (WHO "Option A"): antenatal zidovudine (CD4 <= 350/mu L) or ART (CD4 > 350/mu L). Outcomes included MTCT risk at weaning (age 6 months), maternal and pediatric life expectancy (LE), maternal and pediatric lifetime healthcare costs (2013 USD), and cost-effectiveness ($/life-year saved). Results In the base case, laboratory led to projected MTCT risks of 5.7%, undiscounted pediatric LE of 53.2 years, and undiscounted PMTCT plus pediatric lifetime costs of $1,070/infant. POC led to lower modeled MTCT risk (5.3%), greater pediatric LE (53.4 years) and lower PMTCT plus pediatric lifetime costs ($1,040/infant). Maternal outcomes following laboratory were similar to POC (LE: 21.2 years; lifetime costs: $23,860/person). Compared to laboratory, POC improved clinical outcomes and reduced healthcare costs. Conclusions In antenatal clinics implementing Option A, the higher initial cost of a one-time POC CD4 assay will be offset by cost-savings from prevention of pediatric HIV infection. C1 [Ciaranello, Andrea L.; Freedberg, Kenneth A.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Kelly, Kathleen; Christensen, Sarah; Doherty, Katie; Hou, Taige; Francke, Jordan A.; Freedberg, Kenneth A.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Gen Med, Boston, MA 02114 USA. [Ciaranello, Andrea L.; Hou, Taige; Freedberg, Kenneth A.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Myer, Landon; Daskilewicz, Kristen] Univ Cape Town, Sch Publ Hlth & Family Med, Div Epidemiol & Biostat, ZA-7925 Cape Town, South Africa. [Bekker, Linda-Gail; Wood, Robin] Univ Cape Town, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa. [Wools-Kaloustian, Kara] Indiana Univ Sch Med, Dept Med, Div Infect Dis, Indianapolis, IN 46202 USA. [Freedberg, Kenneth A.; Walensky, Rochelle P.] Harvard Univ, Ctr AIDS Res, Boston, MA 02115 USA. [Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Ciaranello, AL (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. EM aciaranello@partners.org; rwalensky@partners.org FU March of Dimes Foundation; National Institutes of Health (NIAID) [K01 AI078754, R01 AI058736, R01 AI093269]; East African IeDEA Consortium [U01 AI069911]; IMPAACT network [U01 AI068632]; Massachusetts General Hospital Executive Committee on Research; Elizabeth Glaser Pediatric AIDS Foundation; National Institute of Allergy and Infectious Diseases (NIAID); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [N01-DK-9-001/HHSN267200800001C]; National Cancer Institute; National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) [UM1AI068632, UM1AI068616]; National Institute of Mental Health (NIMH) FX This work was supported by the March of Dimes Foundation (ALC, LM, KK, SC, K. Daskilewicz, K. Doherty, LGB, TH), National Institutes of Health (NIAID) (K01 AI078754 (ALC), R01 AI058736 ((KK, K. Doherty, TH, KAF, RPW), R01 AI093269 (KAF, RPW), East African IeDEA Consortium U01 AI069911, starand IMPAACT network U01 AI068632star star (KK, SC, K. Doherty, TH, KAF, RW)), the Massachusetts General Hospital Executive Committee on Research (ALC), and the Elizabeth Glaser Pediatric AIDS Foundation (ALC, LM). Point-of-care CD4 measurement devices for use in the pilot evaluation were donated by Alere Healthcare. The funders and the suppliers of CD4 measurement devices had no role in study design, interpretation of results, or decision to publish. starOverall support for the IeDEA network is provided by the National Institute of Allergy and Infectious Diseases (NIAID), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Cancer Institute. star starOverall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under Award Numbers UM1AI068632 (IMPAACT LOC), UM1AI068616 (IMPAACT SDMC), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Support of the sites was provided by the National Institute of Allergy and Infectious Diseases (NIAID) and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9-001/HHSN267200800001C). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 83 TC 7 Z9 7 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 10 PY 2015 VL 10 IS 3 AR UNSP e0117751 DI 10.1371/journal.pone.0117751 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CD7MX UT WOS:000351275700017 PM 25756498 ER PT J AU Sim, K Sum, MY Navedo, D AF Sim, Kang Sum, Min Yi Navedo, Deborah TI Use of narratives to enhance learning of research ethics in residents and researchers SO BMC MEDICAL EDUCATION LA English DT Article DE Narratives; Research ethics; Engagement; Motivation; Reflective learning ID MEDICINE; MODEL AB Background: Past didactic pedagogy on biomedical research ethics and informed consent in our program had resulted in passive memorization of information and disengaged learning within psychiatry residents and clinical researchers. The question is how do we better motivate and engage learners within the session. Thus, we incorporated narratives into the learning environment and hypothesised that the use of narratives in the teaching of biomedical research ethics and informed consent would be associated with greater engagement, motivation, understanding, reflective learning and effectiveness of the teaching session. Methods: The narratives were chosen from the history of research ethics and the humanities literature related to human subject research. Learners were asked to provide post-session feedback through an anonymised questionnaire on their learning session. An outcomes logic model was used for assessment with focus on immediate outcomes such as engagement, motivation, understanding and reflective learning. Results: Overall, 70.5% (N = 273) of the learners responded to the questionnaire. Amongst the respondents, 92.6% (N = 253) of the participants ranked use of narratives as most helpful in appreciating the historical context of research ethics and informed consent in research. The majority felt engaged (89.8%, N = 245), more motivated to learn (77.5%, N = 212) and better equipped (86.4%, N = 236) about the subject matter. Better appreciation of the learning topic, engagement, motivation to learn, equipping were strongly correlated with the promotion of reflective learning, effectiveness of teaching, promotion of critical thinking and overall positive rating of the teaching session on research ethics (all p < 0.001). Multivariate analyses found that the use of narratives was associated with higher overall rating of the teaching session (p = 0.003) and promotion of critical thinking (p = 0.02). Conclusion: Results revealed that the use of narratives could enhance engagement, appreciation of biomedical research ethics and informed consent, and address underlying motivational factors behind learning and understanding of research ethics. C1 [Sim, Kang] Inst Mental Hlth, Dept Gen Psychiat, Singapore 539747, Singapore. [Sim, Kang; Sum, Min Yi] Inst Mental Hlth, Div Res, Singapore 539747, Singapore. [Navedo, Deborah] Massachusetts Gen Hosp, Inst Hlth Profess, Charlestown Navy Yard, Hlth Profess Educ Program,Ctr Interprofess Studie, Boston, MA 02129 USA. RP Sim, K (reprint author), Inst Mental Hlth, Dept Gen Psychiat, 10 Buangkok View, Singapore 539747, Singapore. EM kang_sim@imh.com.sg NR 22 TC 0 Z9 0 U1 2 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6920 J9 BMC MED EDUC JI BMC Med. Educ. PD MAR 10 PY 2015 VL 15 AR 41 DI 10.1186/s12909-015-0329-y PG 7 WC Education & Educational Research; Education, Scientific Disciplines SC Education & Educational Research GA CD4EB UT WOS:000351034300003 PM 25890045 ER PT J AU Platzer, B Elpek, KG Cremasco, V Baker, K Stout, MM Schultz, C Dehlink, E Shade, KTC Anthony, RM Blumberg, RS Turley, SJ Fiebiger, E AF Platzer, Barbara Elpek, Kutlu G. Cremasco, Viviana Baker, Kristi Stout, Madeleine M. Schultz, Cornelia Dehlink, Eleonora Shade, Kai-Ting C. Anthony, Robert M. Blumberg, Richard S. Turley, Shannon J. Fiebiger, Edda TI IgE/Fc epsilon RI-Mediated Antigen Cross-Presentation by Dendritic Cells Enhances Anti-Tumor Immune Responses SO CELL REPORTS LA English DT Article ID NEONATAL FC-RECEPTOR; IN-VIVO; PROTECTIVE IMMUNITY; IMMUNOGLOBULIN-E; CANCER; IMMUNOTHERAPY; CD8(+); TUMORS; INTERNALIZATION; EXPRESSION AB Epidemiologic studies discovered an inverse association between immunoglobulin E (IgE)-mediated allergies and cancer, implying tumor-protective properties of IgE. However, the underlying immunologic mechanisms remain poorly understood. Antigen cross-presentation by dendritic cells (DCs) is of key importance for anti-tumor immunity because it induces the generation of cytotoxic CD8(+) T lymphocytes (CTLs) with specificity for tumor antigens. We demonstrate that DCs use IgE and Fc epsilon RI, the high-affinity IgE receptor, for cross-presentation and priming of CTLs in response to free soluble antigen at low doses. Importantly, IgE/Fc epsilon RI-mediated cross-presentation is a distinct receptor-mediated pathway because it does not require MyD88 signals or IL-12 induction in DCs. Using passive immunization with tumor antigen-specific IgE and DC-based vaccination experiments, we demonstrate that IgE-mediated cross-presentation significantly improves anti-tumor immunity and induces memory responses in vivo. Our findings suggest a cellular mechanism for the tumor-protective features of IgE and expand the known physiological functions of this immunoglobulin. C1 [Platzer, Barbara; Stout, Madeleine M.; Schultz, Cornelia; Dehlink, Eleonora; Fiebiger, Edda] Harvard Univ, Sch Med, Div Gastroenterol & Nutr, Boston Childrens Hosp, Boston, MA 02115 USA. [Platzer, Barbara; Stout, Madeleine M.; Schultz, Cornelia; Dehlink, Eleonora; Fiebiger, Edda] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Elpek, Kutlu G.; Cremasco, Viviana; Turley, Shannon J.] Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. [Elpek, Kutlu G.; Cremasco, Viviana; Turley, Shannon J.] Dana Farber Canc Inst, AIDS, Boston, MA 02115 USA. [Baker, Kristi; Blumberg, Richard S.] Harvard Univ, Sch Med, Div Gastroenterol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Baker, Kristi; Blumberg, Richard S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Shade, Kai-Ting C.; Anthony, Robert M.] Harvard Univ, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp,Med Sch, Boston, MA 02129 USA. RP Fiebiger, E (reprint author), Harvard Univ, Sch Med, Div Gastroenterol & Nutr, Boston Childrens Hosp, Boston, MA 02115 USA. EM edda.fiebiger@childrens.harvard.edu FU NIH [K01DK093597, DK53056, 5R01 DK074500-08, 2P01AI045757-15, R21 CA182598-01, T32 CA 070083-15, AI075037]; Claudia Adams Barr Award for Innovative Cancer Research; Canadian Institutes of Health Research; Cancer Research Institute fellowship; APART Fellowship of the Austrian Academy of Sciences; Austrian Marshall Plan Foundation; Industriellenvereinigung Kaernten; HDDC [P30DK034854] FX We thank Dr. R. Massol, Dr. N. Anandasabapathy, B. Nelms, and S. Schopoff for suggestions and technical assistance. We also thank the Leusen laboratory for reagents. This work was supported by the NIH (K01DK093597 to B.P.; DK53056 to R.S.B.; 5R01 DK074500-08, 2P01AI045757-15, and R21 CA182598-01 to S.J.T.; T32 CA 070083-15 to V.C.; and AI075037 to E.F.). Further support was provided by the Claudia Adams Barr Award for Innovative Cancer Research (to S.J.T.) and the Canadian Institutes of Health Research (to K.B.). V.C. was supported by a Cancer Research Institute fellowship, E.D. was supported by an APART Fellowship of the Austrian Academy of Sciences, and C.S. was supported by the Austrian Marshall Plan Foundation and the Industriellenvereinigung Kaernten. This work was also supported by HDDC grant P30DK034854 and by an unrestricted gift from the Mead Johnson Nutrition Company to the Division of Gastroenterology and Nutrition, Boston Children's Hospital (to E.F.). NR 37 TC 7 Z9 7 U1 1 U2 5 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 MAR 10 PY 2015 VL 10 IS 9 BP 1487 EP 1495 DI 10.1016/j.celrep.2015.02.015 PG 9 WC Cell Biology SC Cell Biology GA CD0DJ UT WOS:000350740300007 ER PT J AU Medeiros, K O'Connor, M Baicu, CF Fitzgibbons, T Shaw, P Tighe, DA Zile, MR Aurigemma, GP AF Medeiros, Keith O'Connor, Mark Baicu, Catalin F. Fitzgibbons, Timothy Shaw, Peter Tighe, Dennis A. Zile, Michael R. Aurigemma, Gerard P. TI Response to Letters Regarding Article, "Systolic and Diastolic Mechanics in Stress Cardiomyopathy" SO CIRCULATION LA English DT Letter C1 [Medeiros, Keith; O'Connor, Mark; Fitzgibbons, Timothy; Tighe, Dennis A.; Aurigemma, Gerard P.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA 01655 USA. [Baicu, Catalin F.; Zile, Michael R.] Med Univ S Carolina, Dept Med, Div Cardiol, Charleston, SC 29425 USA. [Baicu, Catalin F.; Zile, Michael R.] Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. [Shaw, Peter] Univ Virginia, Sch Med, Dept Med, Div Cardiovasc Med, Charlottesville, VA 22908 USA. RP Medeiros, K (reprint author), Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA 01655 USA. OI Fitzgibbons, Timothy/0000-0003-0229-034X NR 3 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD MAR 10 PY 2015 VL 131 IS 10 BP E372 EP E372 DI 10.1161/CIRCULATIONAHA.114.012819 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CD0NR UT WOS:000350771700005 PM 25753351 ER PT J AU Addisu, F Wondafrash, M Chemali, Z Dejene, T Tesfaye, M AF Addisu, Fikir Wondafrash, Mekitie Chemali, Zeina Dejene, Tariku Tesfaye, Markos TI Length of stay of psychiatric admissions in a general hospital in Ethiopia: a retrospective study SO INTERNATIONAL JOURNAL OF MENTAL HEALTH SYSTEMS LA English DT Article DE Psychiatric admission; Mental illness; Psychiatric care; Length of hospital stay; Sub-Saharan Africa; Ethiopia ID GLOBAL MENTAL-HEALTH; CARE; PATTERNS; COHORT; COMMUNITY; CONSEQUENCES; COMORBIDITY; DISORDER; BALANCE; SERVICE AB Background: In sub-Saharan Africa, the number of psychiatric beds per population is disproportionately low. Moreover, there is a lack of data regarding the patterns of psychiatric admissions and the factors leading to long psychiatric hospitalization in this region. This study aimed to investigate the average length of stay (LOS) and the factors associated with prolonged hospitalizations. Methods: A ten-year retrospective chart review of patients admitted to the psychiatric facility of Jimma University Specialized Hospital in southwest Ethiopia was conducted. The medical charts of 846 admissions spanning the period from January 2001 to December 2010 were reviewed. LOS greater than 21 days was considered as a cut-off point for lengthier stay. Bivariate and multivariable logistic regression analyses were conducted to identify factors independently associated with LOS. Results: The most common discharge diagnoses were schizophrenia and other psychotic disorders (27.6%), and bipolar disorder (23.4%). A global clinical rating taken on discharge showed 90.3% improved outcome. The median (25th, 75th percentiles) LOS was 22 (15, 36) days. Patients with major depressive disorder [aOR = 0.51 (0.32 - 0.81)] and brief psychotic disorder [aOR = 0.52 (0.33 - 0.84)] were less likely than patients with schizophrenia and other psychotic disorders to have long hospital stays. Presence of extrapyramidal side-effects and out of pocket expenditures predicted LOS. Conclusions: Patients with psychoses and bipolar disorder have lengthier hospital stays burdening the cost of care of psychiatric treatment in a general hospital setting. Our findings call for identifying those cases quickly, attending to their needs with evidence-based efficient treatment and for improving and developing an aftercare system such that the utilization of acute inpatient beds, already a scarce resource, could achieve higher efficiency. C1 [Addisu, Fikir; Tesfaye, Markos] Jimma Univ, Dept Psychiat, Jimma, Ethiopia. [Wondafrash, Mekitie] Jimma Univ, Dept Populat & Family Hlth, Jimma, Ethiopia. [Chemali, Zeina] Massachusetts Gen Hosp, Dept Psychiat & Neurol, Boston, MA 02114 USA. [Dejene, Tariku] Jimma Univ, Dept Epidemiol, Jimma, Ethiopia. [Tesfaye, Markos] Univ Munich, Ctr Int Hlth, Munich, Germany. RP Tesfaye, M (reprint author), Jimma Univ, Dept Psychiat, Jimma, Ethiopia. EM tesmarkos@yahoo.com OI Tesfaye, Markos/0000-0002-3351-701X FU Jimma University FX The study was funded by Jimma University. The authors would like to thank the staff of Jimma University Specialized Hospital for their support during data collection. We are grateful to Mr. Yohannes Dibaba for additional support in the statistical analysis of our data. NR 36 TC 1 Z9 1 U1 2 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1752-4458 J9 INT J MENT HEALTH SY JI Int. J. Ment. Health Syst. PD MAR 10 PY 2015 VL 9 AR 13 DI 10.1186/s13033-015-0006-x PG 9 WC Psychiatry SC Psychiatry GA CD3DF UT WOS:000350957300002 PM 25780386 ER PT J AU Ganda, OP AF Ganda, Om P. TI Deciphering Cholesterol Treatment Guidelines A Clinician's Perspective SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 Harvard Univ, Med Sch, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Ganda, OP (reprint author), Harvard Univ, Med Sch, Joslin Diabet Ctr, 1 Joslin Pl,Ste 242, Boston, MA 02215 USA. EM om.ganda@joslin.harvard.edu FU NIDDK NIH HHS [P30 DK036836, DK036836] NR 6 TC 5 Z9 5 U1 0 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 MAR 10 PY 2015 VL 313 IS 10 BP 1009 EP 1010 DI 10.1001/jama.2015.216 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CC8UE UT WOS:000350643100011 PM 25756432 ER PT J AU Holmes, DR Brennan, JM Rumsfeld, JS Dai, D O'Brien, SM Vemulapalli, S Edwards, FH Carroll, J Shahian, D Grover, F Tuzcu, EM Peterson, ED Brindis, RG Mack, MJ AF Holmes, David R., Jr. Brennan, J. Matthew Rumsfeld, John S. Dai, David O'Brien, Sean M. Vemulapalli, Sreekanth Edwards, Fred H. Carroll, John Shahian, David Grover, Fred Tuzcu, E. Murat Peterson, Eric D. Brindis, Ralph G. Mack, Michael J. CA STS ACC TVT Registry TI Clinical Outcomes at 1 Year Following Transcatheter Aortic Valve Replacement SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HIGH-RISK PATIENTS; ACADEMIC RESEARCH CONSORTIUM; END-POINT DEFINITIONS; EDWARDS SAPIEN; CONSENSUS DOCUMENT; PREDICT OUTCOMES; COMPETING RISK; EUROSCORE II; IMPLANTATION; REGISTRY AB IMPORTANCE Introducing new medical devices into routine practice raises concerns because patients and outcomesmay differ from those in randomized trials. OBJECTIVE To update the previous report of 30-day outcomes and present 1-year outcomes following transcatheter aortic valve replacement (TAVR) in the United States. DESIGN, SETTING, AND PARTICIPANTS Data from the Society of Thoracic Surgeons/American College of Cardiology (STS/ACC) Transcatheter Valve Therapies Registry were linked with patient-specific Centers for Medicare & Medicaid Services (CMS) administrative claims data. At 299 US hospitals, 12 182 patients linked with CMS data underwent TAVR procedures performed from November 2011 through June 30, 2013, and the end of the follow-up period was June 30, 2014. EXPOSURE Transcatheter aortic valve replacement. MAIN OUTCOMES AND MEASURES One-year outcomes including mortality, stroke, and rehospitalization were evaluated using multivariate modeling. RESULTS The median age of patients was 84 years and 52% were women, with a median STS Predicted Risk of Operative Mortality (STS PROM) score of 7.1%. Following the TAVR procedure, 59.8% were discharged to home and the 30-day mortality was 7.0% (95% CI, 6.5%-7.4%) (n = 847 deaths). In the first year after TAVR, patients were alive and out of the hospital for a median of 353 days (interquartile range, 312-359 days); 24.4%(n = 2074) of survivors were rehospitalized once and 12.5%(n = 1525) were rehospitalized twice. By 1 year, the overall mortality rate was 23.7%(95% CI, 22.8%-24.5%) (n = 2450 deaths), the stroke rate was 4.1%(95% CI, 3.7%-4.5%) (n = 455 stroke events), and the rate of the composite outcome of mortality and stroke was 26.0%(25.1%-26.8%) (n = 2719 events). Characteristics significantly associated with 1-year mortality included advanced age (hazard ratio [HR] for >= 95 vs <75 years, 1.61 [95% CI, 1.24-2.09]; HR for 85-94 years vs <75 years, 1.35 [95% CI, 1.18-1.55]; and HR for 75-84 years vs < 75 years, 1.23 [95% CI, 1.08-1.41]), male sex (HR, 1.21; 95% CI, 1.12-1.31), end-stage renal disease (HR, 1.66; 95% CI, 1.41-1.95), severe chronic obstructive pulmonary disease (HR, 1.39; 95% CI, 1.25-1.55), nontransfemoral access (HR, 1.37; 95% CI, 1.27-1.48), STS PROM score greater than 15% vs less than 8%(HR, 1.82; 95% CI, 1.60-2.06), and preoperative atrial fibrillation/flutter (HR, 1.37; 95% CI, 1.27-1.48). Compared with men, women had a higher risk of stroke (HR, 1.40; 95% CI, 1.15-1.71). CONCLUSIONS AND RELEVANCE Among patients undergoing TAVR in US clinical practice, at 1-year follow-up, overall mortality was 23.7%, the stroke rate was 4.1%, and the rate of the composite outcome of death and stroke was 26.0%. These findings should be helpful in discussions with patients undergoing TAVR. C1 [Holmes, David R., Jr.] Mayo Clin, Rochester, MN 55905 USA. [Brennan, J. Matthew; Dai, David; O'Brien, Sean M.; Vemulapalli, Sreekanth] Duke Clin Res Inst, Durham, NC USA. [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Edwards, Fred H.] Univ Florida, Jacksonville, FL USA. [Carroll, John; Grover, Fred] Univ Colorado, Denver, CO 80202 USA. [Shahian, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tuzcu, E. Murat] Cleveland Clin, Cleveland, OH 44106 USA. [Peterson, Eric D.] Duke Univ, Med Ctr, Durham, NC USA. [Brindis, Ralph G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mack, Michael J.] Baylor Scott & White Hlth, Plano, TX USA. RP Holmes, DR (reprint author), Mayo Clin, 200 First St SW, Rochester, MN 55905 USA. EM holmes.david@mayo.edu FU American College of Cardiology Foundation's National Cardiovascular Data Registry; Society of Thoracic Surgeons FX The STS/ACC TVT Registry is an initiative of the Society of Thoracic Surgeons and the American College of Cardiology Foundation. This research was supported by the American College of Cardiology Foundation's National Cardiovascular Data Registry and the Society of Thoracic Surgeons. NR 33 TC 88 Z9 88 U1 1 U2 5 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 MAR 10 PY 2015 VL 313 IS 10 BP 1019 EP 1028 DI 10.1001/jama.2015.1474 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CC8UE UT WOS:000350643100017 PM 25756438 ER PT J AU Patel, MR Conte, MS Cutlip, DE Dib, N Geraghty, P Gray, W Hiatt, WR Ho, M Ikeda, K Ikeno, F Jaff, MR Jones, WS Kawahara, M Lookstein, RA Mehran, R Misra, S Norgren, L Olin, JW Povsic, TJ Rosenfield, K Rundback, J Shamoun, F Tcheng, J Tsai, TT Suzuki, Y Vranckx, P Wiechmann, BN White, CJ Yokoi, H Krucoff, MW AF Patel, Manesh R. Conte, Michael S. Cutlip, Donald E. Dib, Nabil Geraghty, Patrick Gray, William Hiatt, William R. Ho, Mami Ikeda, Koji Ikeno, Fumiaki Jaff, Michael R. Jones, W. Schuyler Kawahara, Masayuki Lookstein, Robert A. Mehran, Roxana Misra, Sanjay Norgren, Lars Olin, Jeffrey W. Povsic, Thomas J. Rosenfield, Kenneth Rundback, John Shamoun, Fadi Tcheng, James Tsai, Thomas T. Suzuki, Yuka Vranckx, Pascal Wiechmann, Bret N. White, Christopher J. Yokoi, Hiroyoshi Krucoff, Mitchell W. TI Evaluation and Treatment of Patients With Lower Extremity Peripheral Artery Disease Consensus Definitions From Peripheral Academic Research Consortium (PARC) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review DE amputation; foot; intermittent claudication; leg; myocardial infarction; stroke ID PERCUTANEOUS CORONARY INTERVENTION; AORTIC-VALVE IMPLANTATION; INTER-SOCIETY CONSENSUS; END-POINT DEFINITIONS; STENT THROMBOSIS; STANDARDIZED DEFINITIONS; CLINICAL-OUTCOMES; HEART-ASSOCIATION; LIMB ISCHEMIA; TASK-FORCE AB The lack of consistent definitions and nomenclature across clinical trials of novel devices, drugs, or biologics poses a significant barrier to accrual of knowledge in and across peripheral artery disease therapies and technologies. Recognizing this problem, the Peripheral Academic Research Consortium, together with the U.S. Food and Drug Administration and the Japanese Pharmaceuticals and Medical Devices Agency, has developed a series of pragmatic consensus definitions for patients being treated for peripheral artery disease affecting the lower extremities. These consensus definitions include the clinical presentation, anatomic depiction, interventional outcomes, surrogate imaging and physiological follow-up, and clinical outcomes of patients with lower-extremity peripheral artery disease. Consistent application of these definitions in clinical trials evaluating novel revascularization technologies should result in more efficient regulatory evaluation and best practice guidelines to inform clinical decisions in patients with lower extremity peripheral artery disease. (C) 2015 by the American College of Cardiology Foundation. C1 [Patel, Manesh R.; Povsic, Thomas J.; Tcheng, James; Krucoff, Mitchell W.] Duke Univ, Duke Clin Res Inst, Durham, NC 27710 USA. [Conte, Michael S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Cutlip, Donald E.] Harvard Clin Res Inst, Boston, MA USA. [Cutlip, Donald E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Dib, Nabil] Univ Calif San Diego, San Diego, CA 92103 USA. [Geraghty, Patrick] Washington Univ, Sch Med, St Louis, MO USA. [Gray, William] Cardiovasc Res Fdn, New York, NY USA. [Gray, William] Columbia Univ, Med Ctr, New York, NY USA. [Hiatt, William R.] Univ Colorado, Sch Med, Aurora, CO USA. [Hiatt, William R.] CPC Clin Res, Aurora, CO USA. [Ho, Mami; Kawahara, Masayuki] Pharmaceut & Med Devices Agcy, Office Med Devices 1, Tokyo, Japan. [Ikeda, Koji] Tohoku Univ Hosp, Sendai, Miyagi, Japan. [Ikeno, Fumiaki] Stanford Univ, Palo Alto, CA 94304 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, VasCore, Boston, MA 02114 USA. [Lookstein, Robert A.; Mehran, Roxana; Olin, Jeffrey W.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Misra, Sanjay] Mayo Clin, Rochester, MN USA. [Norgren, Lars] Univ Hosp, Orebro, Sweden. [Rosenfield, Kenneth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rundback, John] Holy Name Med Ctr, Teaneck, NJ USA. [Shamoun, Fadi] Mayo Clin Arizona, Phoenix, AZ USA. [Tsai, Thomas T.] Univ Colorado, Kaiser Permanente Colorado Inst Hlth Res, Denver, CO 80202 USA. [Suzuki, Yuka] Pharmaceut & Med Devices Agcy, Off Med Devices 2, Tokyo, Japan. [Vranckx, Pascal] Cardialysis, Rotterdam, Netherlands. [Wiechmann, Bret N.] Vasc & Intervent Phys, Gainesville, FL USA. [White, Christopher J.] Ochsner Med Ctr, New Orleans, LA USA. [Yokoi, Hiroyoshi] Kokura Mem Hosp, Kitakyuku, Japan. RP Patel, MR (reprint author), Duke Univ, Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27710 USA. EM manesh.patel@duke.edu RI White, Christopher/J-6686-2012 OI White, Christopher/0000-0001-8618-7539 FU Johnson & Johnson Pharmaceutical Research and Development; AstraZeneca; National Heart, Lung, and Blood Institute; Agency for Healthcare Research and Quality; Maquet; Medtronic; Boston Scientific; Abbott Vascular; STENTYS; Celonova; Cordis; Abbott; WL Gore; Mercator; Medicines Company; Cardiovascular Systems Incorporated; CPC Clinical Research; Bayer Healthcare; National Institutes of Health; CSI; DNAVEC; GlaxoSmithKline; Kyushu University; Pluristem; ReNeuron; American Heart Association; Bristol-Myers Squibb; Bristol-Myers Squibb/Sanofi; Lilly/Daiichi Sankyo; Regado Biosciences; Baxter Healthcare; Food and Drug Administration; Cordis Corporation; Bard Peripheral Vascular FX Grants were provided from the industry sponsors and representative listed to the International Society for Cardiovascular Translational Research and the Duke Clinical Research Institute to cover the costs of travel, lodging, and the meeting expenses for academic attendees to the meetings in Silver Spring, Maryland. Dr. Patel has received research grants from Johnson & Johnson Pharmaceutical Research and Development, AstraZeneca, the National Heart, Lung, and Blood Institute, Agency for Healthcare Research and Quality, and Maquet; and has served on the advisory board and/or as a consultant to Bayer Healthcare, Janssen, and Genzyme. Dr. Conte has served as a member of the steering committee for AstraZeneca; and has served as a consultant/advisory board member for Cook Medical and Medtronic. Dr. Dib is the Medical Director of CSI. Dr. Cutlip has received research grants or contracts from Medtronic, Boston Scientific, Abbott Vascular, STENTYS, and Celonova. Dr. Geraghty has served as a consultant and trial principal investigator for Bard/Lutonix; has served as an advisory board member for Bard/Lutonix and Boston Scientific; was on the trial steering committee for Covidien; and has served as a speaker and trial principal investigator for Cook Medical. Dr. Gray has received consultant fees from Cordis, Medtronic, Abbott, Boston Scientific, and WL Gore; and research support from Cordis, Medtronic, Abbott, WL Gore, Mercator, The Medicines Company, and Cardiovascular Systems Incorporated. Dr. Hiatt has received grant support from CPC Clinical Research (a nonprofit affiliate of the University of Colorado), AstraZeneca, Bayer Healthcare, the National Institutes of Health, CSI, DNAVEC, GlaxoSmithKline, Kyushu University, Pluristem, ReNeuron, and Rigel. Dr. Jaff was a noncompensated advisor to Abbott Vascular, Boston Scientific, Cordis Corporation, Covidien Vascular, and Medtronic Vascular; has served as a board member for VIVA Physicians, a 501(c) 3 not-for-profit education and research organization; and has equity investment in Embolitech, Hotspur, Icon Interventional, PQ Bypass, and Vascular Therapies. Dr. Jones has received research grants from the American Heart Association, AstraZeneca, Boston Scientific, and Bristol-Myers Squibb; and has served as an advisory board member for AstraZeneca. Dr. Lookstein has served as a consultant to Boston Scientific, Bayer Healthcare, and Cordis Corporation. Dr. Mehran has received institutional research grant support from The Medicines Company, Bristol-Myers Squibb/Sanofi, Lilly/Daiichi Sankyo, Regado Biosciences, and STENTYS; has served as a consultant to Abbott Vascular, AstraZeneca, Boston Scientific, Covidien, CSL Behring, Janssen (Johnson & Johnson), Maya Medical, and Merck; has served on the advisory board of Covidien, Janssen Pharmaceuticals, Merck, Sanofi, and Endothelix, Inc.; and has equity/is a shareholder in Endothelix, Inc. Dr. Misra was the Chair for the Data Safety and Monitoring Board for the FLEXSTENT study sponsored by CORDIS (modest grant); and received research grants from the National Institute of Health. Dr. Norgren was a steering committee member/consultant for Otsuka Pharma, AnGes, AstraZeneca, and Novartis. Dr.; Olin was on the member steering committee clinical trial on placental stem cells for claudication and medical advisory board for PAD related studies for Pluristem; was on the international steering committee for EUCLID trial and was the site investigator for EUCLID trial for AztraZeneca; was on the steering committee TRA2P trial for Vorapaxar and the medical advisory board for Vorapaxor clinical trials for PAD for Merck; and was on the medical advisory and safety board for Tyrosine Kinase Inhibitors and Cardiovascular Risk for Novartis. Dr. Rundback has served on the clinical events committee for Biotronik and St. Jude; has served as a principal investigator for Covidien and Symbionix; has served as a course director for CSI; and has served as a consultant for Covidien, CSI, Sil Vascular, and Intact Vascular. Dr. Povsic was supported by research grants and received advisory fees from Baxter Healthcare; and has served on the data safety monitoring board of Pluristem, Inc. Dr. Tcheng has served on the advisory board of Philips Medical Systems and Cardiovascular Systems, Inc.; and has received research grants from the Food and Drug Administration. Dr. White has served on the research/advisory board of St. Jude and Neovasc; and has served as the steering committee chair for NCDR CathPVI, as the executive committee co-chair for the BEST trial, and as a member of the steering committee for EUCLID (AstraZeneca). Dr. Wiechmann has served on the advisory boards of Boston Scientific and Bard Peripheral Vascular; has received research funding from The Medicines Company; has served as a consultant to Cordis Corporation, Terumo Medical, and Bard Peripheral Vascular; has received clinical trial support from Cordis Corporation, and Bard Peripheral Vascular; and has an equity interest in PQ Bypass. Dr. Krucoff has received modest consulting fees from Medtronic, CSI, Covidien, Abbott Vascular, and Boston Scientific; and has received significant grant funding from Medtronic, CSI, and Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Dr. Michael H. Criqui, MD, MPH, has served as Guest Editor for this paper. NR 33 TC 27 Z9 28 U1 0 U2 7 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 MAR 10 PY 2015 VL 65 IS 9 BP 931 EP 941 DI 10.1016/j.jacc.2014.12.036 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CC3AO UT WOS:000350216700011 PM 25744011 ER PT J AU Webb, AR Heller, HT Benson, CB Lahav, A AF Webb, Alexandra R. Heller, Howard T. Benson, Carol B. Lahav, Amir TI Mother's voice and heartbeat sounds elicit auditory plasticity in the human brain before full gestation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE auditory; brain; mother's voice; heartbeat; preterm newborns ID NEONATAL INTENSIVE-CARE; LOW-BIRTH-WEIGHT; BIOLOGICAL MATERNAL SOUNDS; CORPUS-CALLOSUM SIZE; PRETERM INFANTS; PREMATURE-INFANTS; SENSORY DEPRIVATION; SPEECH-PERCEPTION; CRITICAL PERIOD; NEWBORN BRAIN AB Brain development is largely shaped by early sensory experience. However, it is currently unknown whether, how early, and to what extent the newborn's brain is shaped by exposure to maternal sounds when the brain is most sensitive to early life programming. The present study examined this question in 40 infants born extremely prematurely (between 25- and 32-wk gestation) in the first month of life. Newborns were randomized to receive auditory enrichment in the form of audio recordings of maternal sounds (including their mother's voice and heartbeat) or routine exposure to hospital environmental noise. The groups were otherwise medically and demographically comparable. Cranial ultrasonography measurements were obtained at 30 +/- 3 d of life. Results show that newborns exposed to maternal sounds had a significantly larger auditory cortex (AC) bilaterally compared with control newborns receiving standard care. The magnitude of the right and left AC thickness was significantly correlated with gestational age but not with the duration of sound exposure. Measurements of head circumference and the widths of the frontal horn (FH) and the corpus callosum (CC) were not significantly different between the two groups. This study provides evidence for experience-dependent plasticity in the primary AC before the brain has reached full-term maturation. Our results demonstrate that despite the immaturity of the auditory pathways, the AC is more adaptive to maternal sounds than environmental noise. Further studies are needed to better understand the neural processes underlying this early brain plasticity and its functional implications for future hearing and language development. C1 [Webb, Alexandra R.; Lahav, Amir] Brigham & Womens Hosp, Dept Pediat Newborn Med, Boston, MA 02115 USA. [Heller, Howard T.; Benson, Carol B.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Lahav, Amir] Harvard Univ, Sch Med, Dept Pediat, MassGen Hosp Children, Boston, MA 02115 USA. RP Lahav, A (reprint author), Brigham & Womens Hosp, Dept Pediat Newborn Med, 75 Francis St, Boston, MA 02115 USA. EM amir@hms.harvard.edu FU Charles H. Hood Foundation; Peter and Elizabeth C. Tower Foundation; Little Giraffe Foundation; Gerber Foundation; Hailey's Hope Foundation FX We thank the families and babies who participated in this study; Anna Alkozei and Katie Rand for their kind assistance in early stages of this work; and Peter Forbes for statistical consultation. This study was supported in part by grants made to A.L. from the Charles H. Hood Foundation, the Peter and Elizabeth C. Tower Foundation, Little Giraffe Foundation, Gerber Foundation, and Hailey's Hope Foundation. NR 103 TC 9 Z9 10 U1 4 U2 24 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 MAR 10 PY 2015 VL 112 IS 10 BP 3152 EP 3157 DI 10.1073/pnas.1414924112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CC8VK UT WOS:000350646500063 PM 25713382 ER PT J AU Lin, CW Chang, LC Tseng, GC Kirkwood, CM Sibille, EL Sweet, RA AF Lin, Chien-Wei Chang, Lun-Ching Tseng, George C. Kirkwood, Caitlin M. Sibille, Etienne L. Sweet, Robert A. TI VSNL1 co-expression networks in aging include calcium signaling, synaptic plasticity, and Alzheimer's disease pathways SO FRONTIERS IN PSYCHIATRY LA English DT Article DE visinin-like 1; visinin-like protein 1; Alzheimer disease; co-expression networks; calcium signaling; synaptic plasticity ID VISININ-LIKE PROTEINS; AMYLOID-BETA-PEPTIDE; COGNITIVE DECLINE; GENE-EXPRESSION; HUMAN BRAIN; SENSOR; CORTEX; TRANSCRIPTOME; DISORDERS; DISCOVERY AB The visinin-like 1 (VSNL1) gene encodes visinin-like protein 1, a peripheral biomarker for Alzheimer disease (AD). Little is known, however, about normal VSNL1 expression in brain and the biologic networks in which it participates. Frontal cortex gray matter obtained from 209 subjects without neurodegenerative or psychiatric illness, ranging in age from 16 to 91, was processed on Affymetrix GeneChip 1.1 ST and Human SNP Array 6.0. VSNL1 expression was unaffected by age and sex, and not significantly associated with SNPs in cis or trans. VSNL1 was significantly co-expressed with genes in pathways for calcium signaling, AD, long-term potentiation, long-term depression, and trafficking of AMPA receptors. The association with AD was driven, in part, by correlation with amyloid precursor protein (APP) expression. These findings provide an unbiased link between VSNL1 and molecular mechanisms of AD, including pathways implicated in synaptic pathology in AD. Whether APP may drive increased VSNL1 expression, VSNL1 drives increased APP expression, or both are downstream of common pathogenic regulators will need to be evaluated in model systems. C1 [Lin, Chien-Wei; Chang, Lun-Ching; Tseng, George C.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15213 USA. [Kirkwood, Caitlin M.; Sibille, Etienne L.; Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. [Sibille, Etienne L.] Univ Toronto, Dept Psychiat, Campbell Family Mental Hlth Res Inst, CAMH, Toronto, ON, Canada. [Sibille, Etienne L.] Univ Toronto, Dept Pharmacol &Toxicol, Campbell Family Mental Hlth Res Inst, CAMH, Toronto, ON, Canada. [Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA USA. RP Sweet, RA (reprint author), Univ Pittsburgh, Dept Psychiat, Biomed Sci Tower,Room W-1645,3811 OHara St, Pittsburgh, PA 15213 USA. EM sweetra@upmc.edu FU BLRD VA [I01 BX000452]; NIA NIH HHS [F31 AG044070, P50 AG005133, R01 AG027224]; NIMH NIH HHS [K02 MH084060, R01 MH071533, R01 MH093723, R21 MH094862] NR 50 TC 3 Z9 4 U1 2 U2 4 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-0640 J9 FRONT PSYCHIATRY JI Front. Psychiatry PD MAR 9 PY 2015 VL 6 AR 30 DI 10.3389/fpsyt.2015.00030 PG 9 WC Psychiatry SC Psychiatry GA CV4BA UT WOS:000364209200001 PM 25806004 ER PT J AU Dirkmann, D Groeben, H Farhan, H Stahl, DL Eikermann, M AF Dirkmann, Daniel Groeben, Harald Farhan, Hassan Stahl, David L. Eikermann, Matthias TI Effects of parecoxib on analgesia benefit and blood loss following open prostatectomy: a multicentre randomized trial SO BMC ANESTHESIOLOGY LA English DT Article DE Analgesics non-opioids; Parecoxib; Analgesics opioids; Morphine; Pain; Postoperative pain ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; POSTOPERATIVE PAIN MANAGEMENT; ADVERSE EVENTS; INHIBITORS PARECOXIB; DOUBLE-BLIND; SURGERY; VALDECOXIB; MORPHINE; SODIUM; ACETAMINOPHEN AB Background: This multi-centre, prospective, randomized, double-blind, placebo-controlled study was designed to test the hypotheses that parecoxib improves patients' postoperative analgesia without increasing surgical blood loss following radical open prostatectomy. Methods: 105 patients (64 +/- 7 years old) were randomized to receive either parecoxib or placebo with concurrent morphine patient controlled analgesia. Cumulative opioid consumption (primary objective) and the overall benefit of analgesia score (OBAS), the modified brief pain inventory short form (m-BPI-sf), the opioid-related symptom distress scale (OR-SDS), and perioperative blood loss (secondary objectives) were assessed. Results: In each group 48 patients received the study medication for 48 hours postoperatively. Parecoxib significantly reduced cumulative opioid consumption by 24% (43 +/- 24.1 mg versus 57 +/- 28 mg, mean +/- SD, p=0.02), translating into improved benefit of analgesia (OBAS: 2(0/4) versus 3(1/5.25), p=0.01), pain severity (m-BPI-sf: 1(1/2) versus 2(2/3), p < 0.01) and pain interference (m-BPI-sf: 1(0/1) versus 1(1/3), p=0.001), as well as reduced opioid-related side effects (OR-SDS score: 0.3(0.075/0.51) versus 0.4(0.2/0.83), p=0.03). Blood loss was significantly higher at 24 hours following surgery in the parecoxib group (4.3 g.dL(-1) (3.6/4.9) versus (3.2 g.dL(-1) (2.4/4.95), p=0.02). Conclusions: Following major abdominal surgery, parecoxib significantly improves patients' perceived analgesia. Parecoxib may however increase perioperative blood loss. Further trials are needed to evaluate the effects of selective cyclooxygenase-2 inhibitors on blood loss. C1 [Dirkmann, Daniel; Eikermann, Matthias] Univ Duisburg Essen, Univ Klinikum Essen, Klin Anesthesiol & Intensivmed, D-45144 Essen, Germany. [Groeben, Harald] Kliniken Essen Mitte, Klin Anesthesiol Intensivmed & Schmerztherapie, D-45136 Essen, Germany. [Farhan, Hassan; Stahl, David L.; Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Dirkmann, D (reprint author), Univ Duisburg Essen, Univ Klinikum Essen, Klin Anesthesiol & Intensivmed, Hufelandstr 55, D-45144 Essen, Germany. EM Daniel.Dirkmann@uk-essen.de RI Stahl, David/E-8015-2015 FU Pfizer, Germany FX The study was funded by Pfizer, Germany. NR 42 TC 8 Z9 8 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2253 J9 BMC ANESTHESIOL JI BMC Anesthesiol. PD MAR 9 PY 2015 VL 15 AR 31 DI 10.1186/s12871-015-0015-y PG 9 WC Anesthesiology SC Anesthesiology GA CD3EF UT WOS:000350960000001 PM 25767411 ER PT J AU Sharpe, HJ Pau, G Dijkgraaf, GJ Basset-Seguin, N Modrusan, Z Januario, T Tsui, V Durham, AB Dlugosz, AA Haverty, PM Bourgon, R Tang, JY Sarin, KY Dirix, L Fisher, DC Rudin, CM Sofen, H Migden, MR Yauch, RL de Sauvage, FJ AF Sharpe, Hayley J. Pau, Gregoire Dijkgraaf, Gerrit J. Basset-Seguin, Nicole Modrusan, Zora Januario, Thomas Tsui, Vickie Durham, Alison B. Dlugosz, Andrzej A. Haverty, Peter M. Bourgon, Richard Tang, Jean Y. Sarin, Kavita Y. Dirix, Luc Fisher, David C. Rudin, Charles M. Sofen, Howard Migden, Michael R. Yauch, Robert L. de Sauvage, Frederic J. TI Genomic Analysis of Smoothened Inhibitor Resistance in Basal Cell Carcinoma SO CANCER CELL LA English DT Article ID HEDGEHOG PATHWAY INHIBITOR; PROTEIN-COUPLED RECEPTOR; MUTATIONAL LANDSCAPE; ACQUIRED-RESISTANCE; SONIC HEDGEHOG; HUMAN HOMOLOG; CANCER; MEDULLOBLASTOMA; VISMODEGIB; ACTIVATION AB Smoothened (SMO) inhibitors are under clinical investigation for the treatment of several cancers. Vismodegib is approved for the treatment of locally advanced and metastatic basal cell carcinoma (BCC). Most BCC patients experience significant clinical benefit on vismodegib, but some develop resistance. Genomic analysis of tumor biopsies revealed that vismodegib resistance is associated with Hedgehog (Hh) pathway reactivation, predominantly through mutation of the drug target SMO and to a lesser extent through concurrent copy number changes in SUFU and GLI2. SMO mutations either directly impaired drug binding or activated SMO to varying levels. Furthermore, we found evidence for intra-tumor heterogeneity, suggesting that a combination of therapies targeting components at multiple levels of the Hh pathway is required to overcome resistance. C1 [Sharpe, Hayley J.; Dijkgraaf, Gerrit J.; Januario, Thomas; Yauch, Robert L.; de Sauvage, Frederic J.] Genentech Inc, Dept Mol Oncol, San Francisco, CA 94080 USA. [Pau, Gregoire; Haverty, Peter M.; Bourgon, Richard] Genentech Inc, Dept Bioinformat & Computat Biol, San Francisco, CA 94080 USA. [Modrusan, Zora] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA. [Tsui, Vickie] Genentech Inc, Dept Discovery Chem, San Francisco, CA 94080 USA. [Basset-Seguin, Nicole] Paris 7 Hop St Louis, F-75010 Paris, France. [Durham, Alison B.; Dlugosz, Andrzej A.] Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA. [Tang, Jean Y.; Sarin, Kavita Y.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Dirix, Luc] Univ Antwerp, Univ Antwerp Hosp, Sint Augustinus Canc Ctr, B-2610 Antwerp, Belgium. [Fisher, David C.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Rudin, Charles M.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Sofen, Howard] Univ Calif Los Angeles, Sch Med, Dept Med Dermatol, Los Angeles, CA 90095 USA. [Migden, Michael R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP de Sauvage, FJ (reprint author), Genentech Inc, Dept Mol Oncol, San Francisco, CA 94080 USA. EM sauvage@gene.com OI Rudin, Charles/0000-0001-5204-3465 FU NCI NIH HHS [P30 CA046592, R01 CA087837] NR 49 TC 47 Z9 49 U1 2 U2 11 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 MAR 9 PY 2015 VL 27 IS 3 BP 327 EP 341 DI 10.1016/j.ccell.2015.02.001 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CD3KL UT WOS:000350977200006 PM 25759019 ER PT J AU Wilson, FH Johannessen, CM Piccioni, F Tamayo, P Kim, JW Van Allen, EM Corsello, SM Capelletti, M Calles, A Butaney, M Sharifnia, T Gabriel, SB Mesirov, JP Hahn, WC Engelman, JA Meyerson, M Root, DE Janne, PA Garraway, LA AF Wilson, Frederick H. Johannessen, Cory M. Piccioni, Federica Tamayo, Pablo Kim, Jong Wook Van Allen, Eliezer M. Corsello, Steven M. Capelletti, Marzia Calles, Antonio Butaney, Mohit Sharifnia, Tanaz Gabriel, Stacey B. Mesirov, Jill P. Hahn, William C. Engelman, Jeffrey A. Meyerson, Matthew Root, David E. Jaenne, Pasi A. Garraway, Levi A. TI A Functional Landscape of Resistance to ALK Inhibition in Lung Cancer SO CANCER CELL LA English DT Article ID HUMAN BREAST-CANCER; EGF RECEPTOR; CRIZOTINIB RESISTANCE; ACQUIRED-RESISTANCE; KINASE INHIBITORS; TARGETED THERAPY; ACTIVATION; CELLS; EML4-ALK; EXPRESSION AB We conducted a large-scale functional genetic study to characterize mechanisms of resistance to ALK inhibition in ALK-dependent lung cancer cells. We identify members of known resistance pathways and additional putative resistance drivers. Among the latter were members of the P2Y purinergic receptor family of G-protein-coupled receptors (P2Y1, P2Y2, and P2Y6). P2Y receptors mediated resistance in part through a protein-kinase-C (PKC)-dependent mechanism. Moreover, PKC activation alone was sufficient to confer resistance to ALK inhibitors, whereas combined ALK and PKC inhibition restored sensitivity. We observed enrichment of gene signatures associated with several resistance drivers (including P2Y receptors) in crizotinib-resistant ALK-rearranged lung tumors compared to treatment-naive controls, supporting a role for these identified mechanisms in clinical ALK inhibitor resistance. C1 [Wilson, Frederick H.; Kim, Jong Wook; Van Allen, Eliezer M.; Corsello, Steven M.; Capelletti, Marzia; Calles, Antonio; Butaney, Mohit; Sharifnia, Tanaz; Hahn, William C.; Meyerson, Matthew; Jaenne, Pasi A.; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Wilson, Frederick H.; Johannessen, Cory M.; Piccioni, Federica; Tamayo, Pablo; Kim, Jong Wook; Van Allen, Eliezer M.; Corsello, Steven M.; Sharifnia, Tanaz; Gabriel, Stacey B.; Mesirov, Jill P.; Hahn, William C.; Meyerson, Matthew; Root, David E.; Garraway, Levi A.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Meyerson, Matthew] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA. [Jaenne, Pasi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA. RP Garraway, LA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM levi_garraway@dfci.harvard.edu OI Calles, Antonio/0000-0002-2547-1947 FU Starr Cancer Consortium [I5-A560]; NIH [DP2 0D002750, 5R33CA155554-03, R01 CA136851, T32 CA009172, R01 CA154480, GM074024]; Huber-Foster fellowship; Conquer Cancer Foundation of ASCO Young Investigator Award; AACR-Bristol-Myers Squibb Oncology Fellowship in Clinical Cancer Research [14-40-15-WILS]; Novartis Institute for BioMedical Research; National Human Genome Research Institute (NHGRI) [5U54HG003067-11]; National Cancer Institute (NCI) [U54 CA112962, U01 CA176058]; Melanoma Research Foundation; LINCS program [U54 HG006093]; Novartis; Bayer FX We thank the patients for their participation in this study. We thank Daniel Lam, Mukta Bagul, and Thomas Nieland for technical assistance. We thank Chandra Pedamallu and Akinyemi Ojesina for assistance with processing RNA-seq data, as well as Deborah Farlow and Samira Bahl for assistance in data management. We thank Ami Bhatt, David Barbie, David Takeda, Andrew Aguirre, Yaara Zwang, Rajiv Narayan, and members of the L.A.G. laboratory for helpful discussions. This work was supported by the Starr Cancer Consortium (I5-A560; L.A.G.), the NIH Director's New Innovator Award (DP2 0D002750; L.A.G.), NIH 5R33CA155554-03 (L.A.G.), NIH R01 CA136851 (P.A.J.), NIH grant T32 CA009172 (F.H.W., S.M.C.), the Huber-Foster fellowship (F.H.W.), the Conquer Cancer Foundation of ASCO Young Investigator Award (F.H.W., S.M.C.), the 2014 AACR-Bristol-Myers Squibb Oncology Fellowship in Clinical Cancer Research (grant 14-40-15-WILS; F.H.W.), a grant from the Novartis Institute for BioMedical Research (L.A.G., W.C.H.), the National Human Genome Research Institute (NHGRI; #5U54HG003067-11; S.B.G., L.A.G.), grants from the National Cancer Institute (NCI; U54 CA112962 and U01 CA176058; W.C.H.), a Career Development Award from the Melanoma Research Foundation (C.M.J.), the LINCS program (U54 HG006093), and NIH R01 CA154480 and GM074024 (J.P.M., P.T.).; L.A.G. is a consultant and equity holder in Foundation Medicine. L.A.G. is a consultant to Novartis, Millenium/Takeda, and Boehringer Ingelheim and a recipient of a grant from Novartis. P.A.J. is a consultant/advisory board member for Abbott Laboratories, AstraZeneca, Boehringer Ingelheim, Chugai, Clovis, Genentech, Pfizer, and Sanofi. W.C.H. is a consultant for Novartis and recipient of a grant from Novartis. M.M. receives research support from Bayer and is a consultant and equity holder in Foundation Medicine. J.A.E. is a consultant/advisory board member of Novartis, GSK, Genentech, and AstraZeneca and a recipient of a grant from Novartis. NR 51 TC 39 Z9 40 U1 7 U2 19 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 MAR 9 PY 2015 VL 27 IS 3 BP 397 EP 408 DI 10.1016/j.ccell.2015.02.005 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CD3KL UT WOS:000350977200011 PM 25759024 ER PT J AU Chen, HX Guan, RN Lei, YP Chen, JY Ge, Q Zhang, XS Dou, RX Chen, HY Liu, H Qi, XL Zhou, XD Chen, CY AF Chen, Hongxia Guan, Runnian Lei, Yupeng Chen, Jianyong Ge, Qi Zhang, Xiaoshen Dou, Ruoxu Chen, Hongyuan Liu, Hao Qi, Xiaolong Zhou, Xiaodong Chen, Changyan TI Lymphangiogenesis in Gastric Cancer regulated through Akt/mTOR-VEGF-C/VEGF-D axis SO BMC CANCER LA English DT Article DE Lymphangiogenesis; Gastric cancer; Akt/mTOR; VEGF ID ENDOTHELIAL GROWTH-FACTOR; LYMPH-NODE METASTASIS; FACTOR-C; PHOSPHORYLATED AKT; MAMMALIAN TARGET; DOWN-REGULATION; FACTOR (VEGF)-C; VESSEL DENSITY; KINASE-B; EXPRESSION AB Background: Lymphangiogenesis plays a significant role in metastasis and recurrence of gastric cancer. There is no report yet focusing on the modulation of VEGF pathway and lymphangiogenesis of gastric cancer by targeting Akt/mTOR pathway. This study aims to demonstrate the relationship between Akt/mTOR pathway and VEGF-C/-D in gastric cancer. Methods: We collected surgically resected gastric adenocarcinoma specimens from 55 consented patients. Immunohistochemistry staining of p-Akt, p-mTOR, VEGF-C, VEGF-D were performed and scored by two independent pathologists. The results were presented as staining intensity and positive staining cell rate. We also measured lymphatic vessel density (LVD) by D2-40 staining. Different dosages of p-Akt inhibitor LY294002 (12.5 mu M, 25 mu M, 50 mu M) and p-mTOR inhibitor Rapamycin (25 nM, 50 nM, 100 nM) were given to gastric cancer cell line SGC-7901 in vitro. The inhibition rate of cell growth was tested by MTT at 24 h, 48 h and 72 h, respectively and protein expressions of Akt, p-Akt, mTOR, p-mTOR, VEGF-C and VEGF-D were examined by Western blot. Results: The positive staining rates of p-Akt, p-mTOR, VEGF-C and VEGF-D in 55 gastric cancer clinical specimens were 74.54%, 85.45%, 72.73% and 58.18%. p-Akt and p-mTOR were positively correlated with VEGF-C and VEGF-D (p < 0.01). The LVD increased with incremental tendency of staining intensity of p-Akt, p-mTOR, VEGF-C and VEGF-D. LY294002 or Rapamycin significantly suppressed SGC-7901 cell growth and the inhibition rate was dose and time dependent (p < 0.001). In addition, the protein expression of p-Akt and p-mTOR were positively correlated with that of VEGF-C and VEGF-D (p < 0.05). Conclusions: The level of LVD in gastric cancer specimens was significant higher than that of normal gastric tissue and was positively correlated with p-Akt, p-mTOR, VEGF-C and VEGF-D. Inhibition of p-Akt and p-mTOR, in vitro, decreased tumor cell VEGF-C and VEGF-D significantly. Therefore, we concluded that lymphangiogenesis of gastric cancer might be related to Akt/mTOR-VEGF-C/VEGF-D axis. C1 [Chen, Hongxia; Lei, Yupeng; Ge, Qi; Qi, Xiaolong; Zhou, Xiaodong; Chen, Changyan] Nanchang Univ, Affiliated Hosp 1, Dept Gastroenterol, Nanchang 330006, Peoples R China. [Guan, Runnian] Kaiping Cent Hosp, Dept Gastroenterol, Kaiping 529300, Peoples R China. [Chen, Jianyong] Jiangxi Prov Peoples Hosp, Dept Gastroenterol, Nanchang 330006, Peoples R China. [Zhang, Xiaoshen; Dou, Ruoxu; Liu, Hao; Qi, Xiaolong] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Zhang, Xiaoshen; Dou, Ruoxu; Liu, Hao; Qi, Xiaolong] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Hongyuan] Guangdong Pharmaceut Univ, Sch Basic Course, Dept Pathogen Biol & Immunol, Guangzhou 510060, Guangdong, Peoples R China. [Chen, Changyan] Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA. RP Qi, XL (reprint author), Nanchang Univ, Affiliated Hosp 1, Dept Gastroenterol, 17 Yongwaizheng St, Nanchang 330006, Peoples R China. EM qixiaolongmd@gmail.com; yfyzxd@163.com FU National Science Foundation Grants of China [81160307]; Jiangxi Science & Technology Pillar Program; Science Foundation for Young Scholars of Jiangxi Province [2007GQY1167]; Voyage Project of Jiangxi Province Science and Technology Association FX The study was supported by funding from National Science Foundation Grants of China (No. 81160307); Jiangxi Science & Technology Pillar Program and the Science Foundation for Young Scholars of Jiangxi Province (No. 2007GQY1167); Voyage Project of Jiangxi Province Science and Technology Association. NR 29 TC 8 Z9 10 U1 3 U2 7 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 MAR 7 PY 2015 VL 15 AR 103 DI 10.1186/s12885-015-1109-0 PG 7 WC Oncology SC Oncology GA CD1WJ UT WOS:000350864900001 PM 25884175 ER PT J AU Doolan, PJ Testa, M Sharp, G Bentefour, EH Royle, G Lu, HM AF Doolan, P. J. Testa, M. Sharp, G. Bentefour, E. H. Royle, G. Lu, H-M TI Patient-specific stopping power calibration for proton therapy planning based on single-detector proton radiography SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE proton radiography; proton therapy; treatment planning; stoichiometric; calibration ID MONTE-CARLO SIMULATIONS; VIVO RANGE VERIFICATION; CT-HOUNSFIELD UNITS; HEAVY-ION CT; COMPUTED-TOMOGRAPHY; TISSUE; SYSTEM; PATH; UNCERTAINTIES; PRINCIPLE AB A simple robust optimizer has been developed that can produce patient-specific calibration curves to convert x-ray computed tomography (CT) numbers to relative stopping powers (HU-RSPs) for proton therapy treatment planning. The difference between a digitally reconstructed radiograph water-equivalent path length (DRRWEPL) map through the x-ray CT dataset and a proton radiograph (set as the ground truth) is minimized by optimizing the HU-RSP calibration curve. The function of the optimizer is validated with synthetic datasets that contain no noise and its robustness is shown against CT noise. Application of the procedure is then demonstrated on a plastic and a real tissue phantom, with proton radiographs produced using a single detector. The mean errors using generic/optimized calibration curves between the DRRWEPL map and the proton radiograph were 1.8/0.4% for a plastic phantom and -2.1/-0.2% for a real tissue phantom. It was then demonstrated that these optimized calibration curves offer a better prediction of the water equivalent path length at a therapeutic depth. We believe that these promising results are suggestive that a single proton radiograph could be used to generate a patient-specific calibration curve as part of the current proton treatment planning workflow. C1 [Doolan, P. J.; Royle, G.] UCL, Dept Med Phys & Bioengn, London, England. [Testa, M.; Sharp, G.; Lu, H-M] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Bentefour, E. H.] IBA, B-1348 Louvain, Belgium. RP Doolan, PJ (reprint author), UCL, Dept Med Phys & Bioengn, London, England. EM paul.doolan.09@ucl.ac.uk FU Engineering and Physical Sciences Research Council (UK); Ion Beam Applications (Louvain-La-Neuve, Belgium); NIH/NCI [PO1 CA21239] FX PD was funded by the Engineering and Physical Sciences Research Council (UK) and Ion Beam Applications (Louvain-La-Neuve, Belgium). MT was funded by grant number NIH/NCI PO1 CA21239. We would also like to acknowledge the operators at Massachusetts General Hospital and Savenor's Butchers, who helped in the construction of the real tissue phantom. NR 35 TC 10 Z9 10 U1 1 U2 7 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 MAR 7 PY 2015 VL 60 IS 5 BP 1901 EP 1917 DI 10.1088/0031-9155/60/5/1901 PG 17 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA CB3LZ UT WOS:000349530700012 PM 25668437 ER PT J AU Wulker, C Sitek, A Prevrhal, S AF Wuelker, Christian Sitek, Arkadiusz Prevrhal, Sven TI Time-of-flight PET image reconstruction using origin ensembles SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE positron emission tomography; reconstruction algorithms; Bayesian reconstruction; Markov chain Monte Carlo methods ID SINGLE SCATTER SIMULATION; EMISSION-TOMOGRAPHY; VOLUME ELEMENTS; EM ALGORITHM; LIKELIHOOD; CHAINS; MCMC AB The origin ensemble (OE) algorithm is a novel statistical method for minimummean- square-error (MMSE) reconstruction of emission tomography data. This method allows one to perform reconstruction entirely in the image domain, i.e. without the use of forward and backprojection operations. We have investigated the OE algorithm in the context of list-mode (LM) time-of-flight (TOF) PET reconstruction. In this paper, we provide a general introduction to MMSE reconstruction, and a statistically rigorous derivation of the OE algorithm. We show how to efficiently incorporate TOF information into the reconstruction process, and how to correct for random coincidences and scattered events. To examine the feasibility of LM-TOF MMSE reconstruction with the OE algorithm, we applied MMSE-OE and standard maximum-likelihood expectation-maximization (ML-EM) reconstruction to LM-TOF phantom data with a count number typically registered in clinical PET examinations. We analyzed the convergence behavior of the OE algorithm, and compared reconstruction time and image quality to that of the EM algorithm. In summary, during the reconstruction process, MMSE-OE contrast recovery (CRV) remained approximately the same, while background variability (BV) gradually decreased with an increasing number of OE iterations. The final MMSE-OE images exhibited lower BV and a slightly lower CRV than the corresponding ML-EM images. The reconstruction time of the OE algorithm was approximately 1.3 times longer. At the same time, the OE algorithm can inherently provide a comprehensive statistical characterization of the acquired data. This characterization can be utilized for further data processing, e. g. in kinetic analysis and image registration, making the OE algorithm a promising approach in a variety of applications. C1 [Wuelker, Christian] Heidelberg Univ, Med Fac Mannheim, D-68167 Mannheim, Germany. [Sitek, Arkadiusz] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Prevrhal, Sven] Philips Res Labs Hamburg, Dept Digital Imaging, D-22335 Hamburg, Germany. RP Wulker, C (reprint author), Heidelberg Univ, Med Fac Mannheim, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany. EM christian.wuelker@gmx.de; sarkadiu@gmail.com; sven.prevrhal@philips.com OI Sitek, Arkadiusz/0000-0002-0677-4002 FU NHLBI NIH HHS [R21 HL106474] NR 34 TC 2 Z9 2 U1 0 U2 8 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 MAR 7 PY 2015 VL 60 IS 5 BP 1919 EP 1944 DI 10.1088/0031-9155/60/5/1919 PG 26 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA CB3LZ UT WOS:000349530700013 PM 25668558 ER PT J AU Jovanovic, M Rooney, MS Mertins, P Przybylski, D Chevrier, N Satija, R Rodriguez, EH Fields, AP Schwartz, S Raychowdhury, R Mumbach, MR Eisenhaure, T Rabani, M Gennert, D Lu, DN Delorey, T Weissman, JS Carr, SA Hacohen, N Regev, A AF Jovanovic, Marko Rooney, Michael S. Mertins, Philipp Przybylski, Dariusz Chevrier, Nicolas Satija, Rahul Rodriguez, Edwin H. Fields, Alexander P. Schwartz, Schraga Raychowdhury, Raktima Mumbach, Maxwell R. Eisenhaure, Thomas Rabani, Michal Gennert, Dave Lu, Diana Delorey, Toni Weissman, Jonathan S. Carr, Steven A. Hacohen, Nir Regev, Aviv TI Dynamic profiling of the protein life cycle in response to pathogens SO SCIENCE LA English DT Article ID DENDRITIC CELL ACTIVATION; MESSENGER-RNA; TEMPORAL DYNAMICS; REVEALS; EXPRESSION; TRANSLATION; YEAST; PRINCIPLES; PROTEOMES; ABUNDANCE AB Protein expression is regulated by the production and degradation of messenger RNAs (mRNAs) and proteins, but their specific relationships remain unknown. We combine measurements of protein production and degradation and mRNA dynamics so as to build a quantitative genomic model of the differential regulation of gene expression in lipopolysaccharide-stimulated mouse dendritic cells. Changes in mRNA abundance play a dominant role in determining most dynamic fold changes in protein levels. Conversely, the preexisting proteome of proteins performing basic cellular functions is remodeled primarily through changes in protein production or degradation, accounting for more than half of the absolute change in protein molecules in the cell. Thus, the proteome is regulated by transcriptional induction for newly activated cellular functions and by protein life-cycle changes for remodeling of preexisting functions. C1 [Jovanovic, Marko; Rooney, Michael S.; Mertins, Philipp; Przybylski, Dariusz; Chevrier, Nicolas; Satija, Rahul; Schwartz, Schraga; Raychowdhury, Raktima; Mumbach, Maxwell R.; Eisenhaure, Thomas; Rabani, Michal; Gennert, Dave; Lu, Diana; Delorey, Toni; Carr, Steven A.; Hacohen, Nir; Regev, Aviv] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Rooney, Michael S.] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Chevrier, Nicolas] Harvard Univ, Harvard Fac Arts & Sci, Ctr Syst Biol, Cambridge, MA 02138 USA. [Rodriguez, Edwin H.; Fields, Alexander P.; Weissman, Jonathan S.] Univ Calif San Francisco, Calif Inst Quantitat Biomed Res, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA. [Eisenhaure, Thomas; Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Weissman, Jonathan S.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA. [Hacohen, Nir] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Regev, Aviv] MIT, Dept Biol, Cambridge, MA 02140 USA. [Regev, Aviv] MIT, Dept Biol, HHMI, Cambridge, MA 02140 USA. RP Regev, A (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM nhacohen@mgh.harvard.edu; aregev@broad.mit.edu FU National Human Genome Research Institute Centers of Excellence in Genomics Science [P50 HG006193]; Broad Institute Funds; NIH Pioneer Award; Klarman Cell Observatory; HHMI; Swiss National Science Foundation (SNF); Marie Sklodowska-Curie International Outgoing Fellowships; NIH Training Program in Bioinformatics and Integrative Genomics training grant; Rothschild Fellowship; European Molecular Biology Organization fellowship; Human Frontier Science Program fellowships; Howard Hughes Medical Institute Gilliam Fellowship for Advanced Study FX We thank members of the Regev, Hacohen, and Carr groups, as well as G. Brar, N. Slavov, and E. Airoldi for constant input and discussions. We thank L. Gaffney for help with the figures and K. Lage and A. Kashani for help with some of the analyses. This work was supported by National Human Genome Research Institute Centers of Excellence in Genomics Science P50 HG006193 (A.R, N.H., S.A.C.) and Broad Institute Funds. A.R. was supported by an NIH Pioneer Award, the Klarman Cell Observatory, and HHMI. M.J. was supported by fellowships of the Swiss National Science Foundation for advanced researchers (SNF) and the Marie Sklodowska-Curie International Outgoing Fellowships. M.S.R. was supported by the NIH Training Program in Bioinformatics and Integrative Genomics training grant. S.S. was supported by a Rothschild Fellowship, a European Molecular Biology Organization fellowship, and Human Frontier Science Program fellowships. E.H.R. was supported by the Howard Hughes Medical Institute Gilliam Fellowship for Advanced Study. Data have been deposited in the Gene Expression Omnibus under accession number GSE59793. The original mass spectra, may be downloaded from MassIVE (http://massive.ucsd.edu) using the identifier MSV000078994. The data are accessible at ftp://MSV000078994:a@massive.ucsd.edu. DogmaQuant is distributed under open source (BSD) license. NR 56 TC 58 Z9 58 U1 4 U2 16 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 MAR 6 PY 2015 VL 347 IS 6226 AR 1259038 DI 10.1126/science.1259038 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CC4WB UT WOS:000350354200045 PM 25745177 ER PT J AU Sharma, RK Baehr, W Makino, CL Duda, T AF Sharma, Rameshwar K. Baehr, Wolfgang Makino, Clint L. Duda, Teresa TI Ca2+ and Ca2+-interlocked membrane guanylate cyclase signal modulation of neuronal and cardiovascular signal transduction SO Frontiers in Molecular Neuroscience LA English DT Editorial Material DE cyclic GMP; Ca2+; membrane guanylate cyclase; multiple transduction modes; signal transduction ID GENE-THERAPY; INSIGHTS; ACTIVATION; MUTATIONS; MODELS; GCAP1; SHAPE C1 [Sharma, Rameshwar K.; Duda, Teresa] Salus Univ, Unit Regulatory & Mol Biol, Res Div Biochem & Mol Biol, Elkins Pk, PA 19027 USA. [Baehr, Wolfgang] Univ Utah, Sch Med, Dept Ophthalmol & Visual Sci, Salt Lake City, UT USA. [Makino, Clint L.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Makino, Clint L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sharma, RK (reprint author), Salus Univ, Unit Regulatory & Mol Biol, Res Div Biochem & Mol Biol, Elkins Pk, PA 19027 USA. EM rsharma@salus.edu OI Makino, Clint/0000-0002-6005-9069 NR 16 TC 2 Z9 2 U1 0 U2 2 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5099 J9 FRONT MOL NEUROSCI JI Front. Molec. Neurosci. PD MAR 6 PY 2015 VL 8 AR 7 DI 10.3389/fnmol.2015.00007 PG 2 WC Neurosciences SC Neurosciences & Neurology GA CG6HW UT WOS:000353401400001 PM 25798085 ER PT J AU Jacobo, SMP Kazlauskas, A AF Jacobo, Sarah Melissa P. Kazlauskas, Andrius TI Insulin-like Growth Factor 1 (IGF-1) Stabilizes Nascent Blood Vessels SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR-I RECEPTOR; LYSOPHOSPHATIDIC ACID; ENDOTHELIAL-CELLS; RETINAL NEOVASCULARIZATION; VASCULAR MORPHOGENESIS; DIABETIC-RETINOPATHY; ANGIOGENESIS; ACTIVATION; REGRESSION; MIGRATION AB Here we report that VEGF-A and IGF-1 differ in their ability to stabilize newly formed blood vessels and endothelial cell tubes. Although VEGF-A failed to support an enduring vascular response, IGF-1 stabilized neovessels generated from primary endothelial cells derived from various vascular beds and mouse retinal explants. In these experimental systems, destabilization/regression was driven by lysophosphatidic acid (LPA). Because previous studies have established that Erk antagonizes LPA-mediated regression, we considered whether Erk was an essential component of IGF-dependent stabilization. Indeed, IGF-1 lost its ability to stabilize neovessels when the Erk pathway was inhibited pharmacologically. Furthermore, stabilization was associated with prolonged Erk activity. In the presence of IGF-1, Erk activity persisted longer than in the presence of VEGF or LPA alone. These studies reveal that VEGF and IGF-1 can have distinct inputs in the angiogenic process. In contrast to VEGF, IGF-1 stabilizes neovessels, which is dependent on Erk activity and associated with prolonged activation. C1 [Kazlauskas, Andrius] Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Kazlauskas, A (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02115 USA. EM andrius_kazlauskas@meei.harvard.edu OI Jacobo, Sarah Melissa/0000-0002-1341-7222 FU Knights Templar Eye Foundation Early Career Award FX This work was supported by a Knights Templar Eye Foundation Early Career Award (to S. M. P. J.). NR 53 TC 8 Z9 9 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 6 PY 2015 VL 290 IS 10 BP 6349 EP 6360 DI 10.1074/jbc.M114.634154 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CD0AO UT WOS:000350732500040 PM 25564613 ER PT J AU Abou Hassan, OK Fahed, AC Batrawi, M Arabi, M Refaat, MM DePalma, SR Seidman, JG Seidman, CE Bitar, FF Nemer, GM AF Abou Hassan, Ossama K. Fahed, Akl C. Batrawi, Manal Arabi, Mariam Refaat, Marwan M. DePalma, Steven R. Seidman, J. G. Seidman, Christine E. Bitar, Fadi F. Nemer, Georges M. TI NKX2-5 Mutations in an Inbred Consanguineous Population: Genetic and Phenotypic Diversity SO SCIENTIFIC REPORTS LA English DT Article ID CONGENITAL HEART-DISEASE; CARDIAC CONDUCTION SYSTEM; ATRIAL-FIBRILLATION; TRANSCRIPTION FACTORS; PRESSURE-OVERLOAD; HOMEODOMAIN; ASSOCIATION; DEFECTS; NETWORK; BLOCK AB NKX2-5 mutations are associated with different forms of congenital heart disease. Despite the knowledge gained from molecular and animal studies, genotype-phenotype correlations in humans are limited by the lack of large cohorts and the incomplete assessment of family members. We hypothesized that studying the role of NKX2-5 in inbred populations with homogeneous genetic backgrounds and high consanguinity rates such as Lebanon could help closing this gap. We sequenced NKX2-5 in 188 index CHD cases (25 with ASD). Five variants (three segregated in families) were detected in eleven families including the previously documented p.R25C variant, which was found in seven patients from different families, and in one healthy individual. In 3/5 familial dominant ASD cases, we identified an NKX2-5 mutation. In addition to the heterogeneity of NKX2-5 mutations, a diversity of phenotypes occurred within the families with predominant ASD and AV block. We did in fact identify a large prevalence of Sudden Cardiac Death (SCD) in families with truncating mutations, and two patients with coronary sinus disease. NKX2-5 is thus responsible for dominant familial ASD even in consanguineous populations, and a wide genetic and phenotypic diversity is characteristic of NKX2-5 mutations in the Lebanese population. C1 [Abou Hassan, Ossama K.; Batrawi, Manal; Refaat, Marwan M.; Bitar, Fadi F.; Nemer, Georges M.] Amer Univ Beirut, Dept Biochem & Mol Genet, Beirut, Lebanon. [Fahed, Akl C.; DePalma, Steven R.; Seidman, J. G.; Seidman, Christine E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Fahed, Akl C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Arabi, Mariam; Bitar, Fadi F.] Amer Univ Beirut, Dept Pediat & Adolescent Med, Beirut, Lebanon. [Refaat, Marwan M.] Amer Univ Beirut, Dept Internal Med, Beirut, Lebanon. [Seidman, J. G.] Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Seidman, J. G.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. RP Bitar, FF (reprint author), Amer Univ Beirut, Dept Biochem & Mol Genet, Beirut, Lebanon. EM fadi.bitar@aub.edu.lb; georges.nemer@aub.edu.lb OI Nemer, Georges/0000-0003-2157-5279 FU Dubai Harvard Foundation for Medical Research (DHFMR) FX We thank the families for their contribution to this research. We also thank members of the Congenital Heart Disease Genetic Program (CHDGP) especially Ms. Jane Bou Diab, and Ms. Inaam El-Rassy from the Molecular Core Facility at AUB for their technical assistance. This work is supported by a grant from the Dubai Harvard Foundation for Medical Research (DHFMR). We are also grateful for Dr. Alexander G. Bick for his help with CNV analysis. NR 52 TC 4 Z9 4 U1 0 U2 8 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 MAR 6 PY 2015 VL 5 AR 8848 DI 10.1038/srep08848 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CC6LM UT WOS:000350476400001 PM 25742962 ER PT J AU Schram, AM Campigotto, F Mullally, A Fogerty, A Massarotti, E Neuberg, D Berliner, N AF Schram, Alison M. Campigotto, Federico Mullally, Ann Fogerty, Annemarie Massarotti, Elena Neuberg, Donna Berliner, Nancy TI Marked hyperferritinemia does not predict for HLH in the adult population SO BLOOD LA English DT Article ID SERUM FERRITIN LEVELS; HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; IRON-DEFICIENCY; ANTIPHOSPHOLIPID SYNDROME; CELLULAR-REGULATION; STILLS-DISEASE; DIAGNOSIS; GUIDELINES; OVERLOAD AB Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of uncontrolled immune activation that has gained increasing attention during the last decade. The diagnosis of HLH is based on a constellation of clinical and laboratory abnormalities, including elevated serum ferritin levels. In the pediatric population, marked hyperferritinemia is specific for HLH. To determine what conditions are associated with profoundly elevated ferritin in the adult population, we performed a retrospective analysis in a large academic health care system. We identified 113 patients with serum ferritin levels higher than 50 000 mu g/L. The most frequently observed conditions included renal failure, hepatocellular injury, infections, and hematologic malignancies. Our results suggest that marked hyperferritinemia can be seen in a variety of conditions and is not specific for HLH in adults. C1 [Schram, Alison M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Campigotto, Federico; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Mullally, Ann; Berliner, Nancy] Harvard Univ, Brigham & Womens Hosp, Div Hematol, Dept Med,Med Sch, Boston, MA 02115 USA. [Fogerty, Annemarie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol,Dept Med, Boston, MA USA. [Massarotti, Elena] Harvard Univ, Brigham & Womens Hosp, Dept Med, Div Rheumatol,Med Sch, Boston, MA 02115 USA. RP Berliner, N (reprint author), Brigham & Womens Hosp, Div Hematol, 75 Francis St,Midcampus 3, Boston, MA 02115 USA. EM nberliner@partners.org OI Schram, Alison/0000-0002-6070-2413 NR 30 TC 25 Z9 26 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAR 5 PY 2015 VL 125 IS 10 BP 1548 EP 1552 DI 10.1182/blood-2014-10-602607 PG 5 WC Hematology SC Hematology GA CI3AM UT WOS:000354619800012 PM 25573993 ER PT J AU Dahlem, MA Schmidt, B Bojak, I Boie, S Kneer, F Hadjikhani, N Kurths, J AF Dahlem, Markus A. Schmidt, Bernd Bojak, Ingo Boie, Sebastian Kneer, Frederike Hadjikhani, Nouchine Kurths, Juergen TI Cortical hot spots and labyrinths: why cortical neuromodulation for episodic migraine with aura should be personalized SO FRONTIERS IN COMPUTATIONAL NEUROSCIENCE LA English DT Article DE migraine; reaction-diffusion; spreading depression; gyrification; neuromodulation ID REACTION-DIFFUSION SYSTEMS; SURFACE-BASED ANALYSIS; PRIMARY VISUAL-CORTEX; SPREADING DEPRESSION; CURVED SURFACES; CEREBRAL-CORTEX; INTERSUBJECT VARIABILITY; COORDINATE SYSTEM; EXCITATION WAVES; AUDITORY-CORTEX AB Stimulation protocols for medical devices should be rationally designed. For episodic migraine with aura we outline model-based design strategies toward preventive and acute therapies using stereotactic cortical neuromodulation. To this end, we regard a localized spreading depression (SD) wave segment as a central element in migraine pathophysiology. To describe nucleation and propagation features of the SD wave segment, we define the new concepts of cortical hot spots and labyrinths, respectively. In particular, we firstly focus exclusively on curvature-induced dynamical properties by studying a generic reaction-diffusion model of SD on the folded cortical surface. This surface is described with increasing level of details, including finally personalized simulations using patient's magnetic resonance imaging (MRI) scanner readings. At this stage, the only relevant factor that can modulate nucleation and propagation paths is the Gaussian curvature, which has the advantage of being rather readily accessible by MRI. We conclude with discussing further anatomical factors, such as areal, laminar, and cellular heterogeneity, that in addition to and in relation to Gaussian curvature determine the generalized concept of cortical hot spots and labyrinths as target structures for neuromodulation. Our numerical simulations suggest that these target structures are like fingerprints, they are individual features of each migraine sufferer. The goal in the future will be to provide individualized neural tissue simulations. These simulations should predict the clinical data and therefore can also serve as a test bed for exploring stereotactic cortical neuromodulation. C1 [Dahlem, Markus A.; Schmidt, Bernd; Kurths, Juergen] Humboldt Univ, Dept Phys, D-10115 Berlin, Germany. [Dahlem, Markus A.] Max Planck Inst Phys Komplexer Syst, Dept Biol Phys, Dresden, Germany. [Bojak, Ingo] Univ Reading, Sch Syst Engn, Cybernet Res Grp, Reading, Berks, England. [Boie, Sebastian] Univ Auckland, Dept Math, Auckland 1, New Zealand. [Kneer, Frederike] Tech Univ Berlin, Dept Software Engn & Theoret Comp Sci, Berlin, Germany. [Hadjikhani, Nouchine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Kurths, Juergen] Potsdam Inst Climate Impact Res, Potsdam, Germany. [Kurths, Juergen] Univ Aberdeen, Inst Complex Syst & Math Biol, Aberdeen, Scotland. RP Dahlem, MA (reprint author), Humboldt Univ, AG NLD Cardiovasc Phys, Robert Koch Pl 4, D-10115 Berlin, Germany. EM dahlem@physik.hu-berlin.de RI Bojak, Ingo/E-9759-2010; OI Bojak, Ingo/0000-0003-1765-3502; Hadjikhani, Nouchine/0000-0003-4075-3106; Boie, Sebastian/0000-0001-7993-7901 FU Bun desministerium fur Bildung und Forschung [BMBF 01GQ1109, BMBF 01GQ1001A] FX This work was supported by the Bun desministerium fur Bildung und Forschung (BMBF 01GQ1109 and BMBF 01GQ1001A). NR 84 TC 2 Z9 2 U1 0 U2 7 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5188 J9 FRONT COMPUT NEUROSC JI Front. Comput. Neurosci. PD MAR 5 PY 2015 VL 9 AR UNSP 29 DI 10.3389/fncom.2015.00029 PG 13 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA CF3QA UT WOS:000352462400001 PM 25798103 ER PT J AU Barclay, LA Wales, TE Garner, TP Wachter, F Lee, S Guerra, RM Stewart, ML Braun, CR Bird, GH Gavathiotis, E Engen, JR Walensky, LD AF Barclay, Lauren A. Wales, Thomas E. Garner, Thomas P. Wachter, Franziska Lee, Susan Guerra, Rachel M. Stewart, Michelle L. Braun, Craig R. Bird, Gregory H. Gavathiotis, Evripidis Engen, John R. Walensky, Loren D. TI Inhibition of Pro-Apoptotic BAX by a Noncanonical Interaction Mechanism SO MOLECULAR CELL LA English DT Article ID BCL-2 FAMILY; BIOPHYSICAL CHARACTERIZATION; PROTEIN INTERACTIONS; HYDROGEN-EXCHANGE; MASS-SPECTROMETRY; PROAPOPTOTIC BAX; BH4 DOMAIN; IN-VIVO; ACTIVATION; PEPTIDES AB BCL-2 is a negative regulator of apoptosis implicated in homeostatic and pathologic cell survival. The canonical anti-apoptotic mechanism involves entrapment of activated BAX by a groove on BCL-2, preventing BAX homo-oligomerization and mitochondrial membrane poration. The BCL-2 BH4 domain also confers anti-apoptotic functionality, but the mechanism is unknown. We find that a synthetic a-helical BH4 domain binds to BAX with nanomolar affinity and independently inhibits the conformational activation of BAX. Hydrogen-deuterium exchange mass spectrometry demonstrated that the N-terminal conformational changes in BAX induced by a triggering BIM BH3 helix were suppressed by the BCL-2 BH4 helix. Structural analyses localized the BH4 interaction site to a groove formed by residues of alpha 1, alpha 1-alpha 2 loop, and alpha 2-alpha 3 and alpha 5-alpha 6 hairpins on the BAX surface. These data reveal a previously unappreciated binding site for targeted inhibition of BAX and suggest that the BCL-2 BH4 domain may participate in apoptosis blockade by a noncanonical interaction mechanism. C1 [Barclay, Lauren A.; Wachter, Franziska; Lee, Susan; Guerra, Rachel M.; Stewart, Michelle L.; Braun, Craig R.; Bird, Gregory H.; Walensky, Loren D.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Barclay, Lauren A.; Wachter, Franziska; Lee, Susan; Guerra, Rachel M.; Stewart, Michelle L.; Braun, Craig R.; Bird, Gregory H.; Walensky, Loren D.] Dana Farber Canc Inst, Linde Program Canc Chem Biol, Boston, MA 02215 USA. [Wales, Thomas E.; Engen, John R.] Northeastern Univ, Barnett Inst Chem & Biol Anal, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Garner, Thomas P.; Gavathiotis, Evripidis] Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA. RP Walensky, LD (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. EM loren_walensky@dfci.harvard.edu FU NIH [5R01CA050239, 5R01GM090299, R01GM086507, R01GM101135, R00HL095929]; NSF; Kimmel Scholar Award; Sinsheimer Scholar Award; NYSTAR; [T32GM007306] FX We thank E. Smith for editorial and graphics assistance, and S. Cahill for NMR technical support (Albert Einstein College of Medicine Structural NMR Resource). This work was supported by NIH grants 5R01CA050239 and 5R01GM090299 to L.D.W., NIH grants R01GM086507 and R01GM101135 to J.R.E., an NSF Graduate Research Fellowship to L.A.B., additional support to L.A.B. from T32GM007306, and NIH grant R00HL095929, a Kimmel Scholar Award, and a Sinsheimer Scholar Award to E.G. Additionally, E.G is a member of the New York Structural Biology Center (NYSBC), and the data collected at NYSBC was made possible by a grant from NYSTAR. L.D.W. is a scientific advisory board member and consultant for Aileron Therapeutics. J.R.E. is a consultant for the Waters Corporation. NR 36 TC 22 Z9 23 U1 0 U2 6 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 MAR 5 PY 2015 VL 57 IS 5 BP 873 EP 886 DI 10.1016/j.molcel.2015.01.014 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CE3GO UT WOS:000351714900012 PM 25684204 ER PT J AU McMillan, BJ Schnute, B Ohlenhard, N Zimmerman, B Miles, L Beglova, N Klein, T Blacklow, SC AF McMillan, Brian J. Schnute, Bjoern Ohlenhard, Nadja Zimmerman, Brandon Miles, Laura Beglova, Natalia Klein, Thomas Blacklow, Stephen C. TI A Tail of Two Sites: A Bipartite Mechanism for Recognition of Notch Ligands by Mind Bomb E3 Ligases SO MOLECULAR CELL LA English DT Article ID UBIQUITIN LIGASE; INTRACELLULAR MOTIFS; DROSOPHILA; DELTA; SERRATE; ENDOCYTOSIS; PROTEIN; SYSTEM; DIFFERENTIATION; MORPHOGENESIS AB Mind bomb (Mib) proteins are large, multi-domain E3 ligases that promote ubiquitination of the cytoplasmic tails of Notch ligands. This ubiquitination step marks the ligand proteins for epsin-dependent endocytosis, which is critical for in vivo Notch receptor activation. We present here crystal structures of the substrate recognition domains of Mib1, both in isolation and in complex with peptides derived from Notch ligands. The structures, in combination with biochemical, cellular, and in vivo assays, show that Mib1 contains two independent substrate recognition domains that engage two distinct epitopes from the cytoplasmic tail of the ligand Jagged1, one in the intracellular membrane proximal region and the other near the C terminus. Together, these studies provide insights into the mechanism of ubiquitin transfer by Mind bomb E3 ligases, illuminate a key event in ligand-induced activation of Notch receptors, and identify a potential target for therapeutic modulation of Notch signal transduction in disease. C1 [McMillan, Brian J.; Zimmerman, Brandon; Miles, Laura; Beglova, Natalia; Blacklow, Stephen C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Schnute, Bjoern; Ohlenhard, Nadja; Klein, Thomas] Univ Dusseldorf, D-40225 Dusseldorf, Germany. [Zimmerman, Brandon; Miles, Laura; Blacklow, Stephen C.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Beglova, Natalia] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Blacklow, SC (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM Stephen_Blacklow@hms.harvard.edu FU NIH [P01 CA119070, R01 CA092433]; American Cancer Society fellowship [120246-PF-11-044-01-DMC]; Deutsche Forschungsgemeinschaft (DFG) [KL 1028/3-1]; U.S. DOE [DE-AC02-06CH11357] FX This work was supported in part by NIH grants P01 CA119070 (Subproject 3 to S.C.B.) and R01 CA092433 (to S.C.B.) and by American Cancer Society fellowship 120246-PF-11-044-01-DMC (to B.J.M). The work of T.K., B.S., and N.O. was supported by the Deutsche Forschungsgemeinschaft (DFG) through Sachbeihilfe KL 1028/3-1. X-ray crystallography was performed at the Advanced Photon Source, an Office of Science User Facility supported by the U.S. DOE under Contract No. DE-AC02-06CH11357. SAXS was conducted at the Advanced Light Source (ALS), a national user facility supported by the DOE. We thank Kelly Arnett for helpful discussions and critical review of the manuscript. NR 43 TC 5 Z9 5 U1 0 U2 4 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 MAR 5 PY 2015 VL 57 IS 5 BP 912 EP 924 DI 10.1016/j.molcel.2015.01.019 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CE3GO UT WOS:000351714900015 PM 25747658 ER PT J AU Orkin, SH AF Orkin, Stuart H. TI 2014 William Allan Award: A Hematologist's Pursuit of Hemoglobin Genetics SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Editorial Material ID BETA-GLOBIN GENE; SICKLE-CELL-DISEASE; FETAL-HEMOGLOBIN; DNA; BCL11A; ASSOCIATION; THALASSEMIA; EXPRESSION; MUTATION; LINEAGE C1 [Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston Childrens Hosp,Canc & Blood Disorders Ctr, Boston, MA 02215 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02215 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston Childrens Hosp,Canc & Blood Disorders Ctr, Boston, MA 02215 USA. EM stuart_orkin@dfci.harvard.edu NR 20 TC 0 Z9 0 U1 0 U2 1 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 MAR 5 PY 2015 VL 96 IS 3 BP 354 EP 360 DI 10.1016/j.ajhg.2014.12.007 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA CD0GD UT WOS:000350747800003 PM 25748351 ER PT J AU Palotie, A AF Palotie, Aarno TI 2014 Curt Stern Award Introduction: Mark Daly SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Editorial Material C1 [Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland, FIN-00014 Helsinki, Finland. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Palotie, Aarno] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Palotie, Aarno] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Palotie, Aarno] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Palotie, A (reprint author), Univ Helsinki, Inst Mol Med Finland, FIN-00014 Helsinki, Finland. EM aarno.palotie@helsinki.fi NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR 5 PY 2015 VL 96 IS 3 BP 367 EP 368 DI 10.1016/j.ajhg.2014.12.018 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA CD0GD UT WOS:000350747800006 PM 25748354 ER PT J AU Daly, MJ AF Daly, Mark J. TI 2014 Curt Stern Award: A Tryst with Genetics SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Editorial Material C1 [Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Daly, Mark J.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Daly, Mark J.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Daly, Mark J.] Univ Helsinki, Inst Mol Med Finland, FIN-00014 Helsinki, Finland. RP Daly, MJ (reprint author), Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. EM mjdaly@atgu.mgh.harvard.edu NR 0 TC 1 Z9 1 U1 0 U2 1 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 MAR 5 PY 2015 VL 96 IS 3 BP 369 EP 371 DI 10.1016/j.ajhg.2014.12.028 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA CD0GD UT WOS:000350747800007 PM 25748355 ER PT J AU Machiela, MJ Zhou, WY Sampson, JN Dean, MC Jacobs, KB Black, A Brinton, LA Chang, IS Chen, C Chen, C Chen, KX Cook, LS Bou, MC De Vivo, I Doherty, J Friedenreich, CM Gaudet, MM Haiman, CA Hankinson, SE Hartge, P Henderson, BE Hong, YC Hosgood, HD Hsiung, CA Hu, W Hunter, DJ Jessop, L Kim, HN Kim, YH Kim, YT Klein, R Kraft, P Lan, Q Lin, DX Liu, JJ Le Marchand, L Liang, XL Lissowska, J Lu, LG Magliocco, AM Matsuo, K Olson, SH Orlow, I Park, JY Pooler, L Prescott, J Rastogi, R Risch, HA Schumacher, F Seow, A Setiawan, VW Shen, HB Sheng, X Shin, MH Shu, XO VanDen Berg, D Wang, JC Wentzensen, N Wong, MP Wu, C Wu, TC Wu, YL Xia, L Yang, HP Yang, PC Zheng, W Zhou, BS Abnet, CC Albanes, D Aldrich, MC Amos, C Amundadottir, LT Berndt, SI Blot, WJ Bock, CH Bracci, PM Burdett, L Buring, JE Butler, MA Carreon, T Chatterjee, N Chung, CC Cook, MB Cullen, M Davis, FG Ding, T Duell, EJ Epstein, CG Fan, JH Figueroa, JD Fraumeni, JF Freedman, ND Fuchs, CS Gao, YT Gapstur, SM Patino-Garcia, A Garcia-Closas, M Gaziano, JM Giles, GG Gillanders, EM Giovannucci, EL Goldin, L Goldstein, AM Greene, MH Hallmans, G Harris, CC Henriksson, R Holly, EA Hoover, RN Hu, N Hutchinson, A Jenab, M Johansen, C Khaw, KT Koh, WP Kolonel, LN Kooperberg, C Krogh, V Kurtz, RC LaCroix, A Landgren, A Landi, MT Li, DH Liao, LM Malats, N McGlynn, KA McNeill, LH McWilliams, RR Melin, BS Mirabello, L Peplonska, B Peters, U Petersen, GM Prokunina-Olsson, L Purdue, M Qiao, YL Rabe, KG Rajaraman, P Real, FX Riboli, E Rodriguez-Santiago, B Rothman, N Ruder, AM Savage, SA Schwartz, AG Schwartz, KL Sesso, HD Severi, G Silverman, DT Spitz, MR Stevens, VL Stolzenberg-Solomon, R Stram, D Tang, ZZ Taylor, PR Teras, LR Tobias, GS Viswanathan, K Wacholder, S Wang, ZM Weinstein, SJ Wheeler, W White, E Wiencke, JK Wolpin, BM Wu, XF Wunder, JS Yu, K Zanetti, KA Zeleniuch-Jacquotte, A Ziegler, RG De Andrade, M Barnes, KC Beaty, TH Bierut, LJ Desch, KC Doheny, KF Feenstra, B Ginsburg, D Heit, JA Kang, JH Laurie, CA Li, JZ Lowe, WL Marazita, ML Melbye, M Mirel, DB Murray, JC Nelson, SC Pasquale, LR Rice, K Wiggs, JL Wise, A Tucker, M Perez-Jurado, LA Laurie, CC Caporaso, NE Yeager, M Chanock, SJ AF Machiela, Mitchell J. Zhou, Weiyin Sampson, Joshua N. Dean, Michael C. Jacobs, Kevin B. Black, Amanda Brinton, Louise A. Chang, I-Shou Chen, Chu Chen, Constance Chen, Kexin Cook, Linda S. Bou, Marta Crous De Vivo, Immaculata Doherty, Jennifer Friedenreich, Christine M. Gaudet, Mia M. Haiman, Christopher A. Hankinson, Susan E. Hartge, Patricia Henderson, Brian E. Hong, Yun-Chul Hosgood, H. Dean, III Hsiung, Chao A. Hu, Wei Hunter, David J. Jessop, Lea Kim, Hee Nam Kim, Yeul Hong Kim, Young Tae Klein, Robert Kraft, Peter Lan, Qing Lin, Dongxin Liu, Jianjun Le Marchand, Loic Liang, Xiaolin Lissowska, Jolanta Lu, Lingeng Magliocco, Anthony M. Matsuo, Keitaro Olson, Sara H. Orlow, Irene Park, Jae Yong Pooler, Loreall Prescott, Jennifer Rastogi, Radhai Risch, Harvey A. Schumacher, Fredrick Seow, Adeline Setiawan, Veronica Wendy Shen, Hongbing Sheng, Xin Shin, Min-Ho Shu, Xiao-Ou VanDen Berg, David Wang, Jiu-Cun Wentzensen, Nicolas Wong, Maria Pik Wu, Chen Wu, Tangchun Wu, Yi-Long Xia, Lucy Yang, Hannah P. Yang, Pan-Chyr Zheng, Wei Zhou, Baosen Abnet, Christian C. Albanes, Demetrius Aldrich, Melinda C. Amos, Christopher Amundadottir, Laufey T. Berndt, Sonja I. Blot, William J. Bock, Cathryn H. Bracci, Paige M. Burdett, Laurie Buring, Julie E. Butler, Mary A. Carreon, Tania Chatterjee, Nilanjan Chung, Charles C. Cook, Michael B. Cullen, Michael Davis, Faith G. Ding, Ti Duell, Eric J. Epstein, Caroline G. Fan, Jin-Hu Figueroa, Jonine D. Fraumeni, Joseph F., Jr. Freedman, Neal D. Fuchs, Charles S. Gao, Yu-Tang Gapstur, Susan M. Patino-Garcia, Ana Garcia-Closas, Montserrat Gaziano, J. Michael Giles, Graham G. Gillanders, Elizabeth M. Giovannucci, Edward L. Goldin, Lynn Goldstein, Alisa M. Greene, Mark H. Hallmans, Goran Harris, Curtis C. Henriksson, Roger Holly, Elizabeth A. Hoover, Robert N. Hu, Nan Hutchinson, Amy Jenab, Mazda Johansen, Christoffer Khaw, Kay-Tee Koh, Woon-Puay Kolonel, Laurence N. Kooperberg, Charles Krogh, Vittorio Kurtz, Robert C. LaCroix, Andrea Landgren, Annelie Landi, Maria Teresa Li, Donghui Liao, Linda M. Malats, Nuria McGlynn, Katherine A. McNeill, Lorna H. McWilliams, Robert R. Melin, Beatrice S. Mirabello, Lisa Peplonska, Beata Peters, Ulrike Petersen, Gloria M. Prokunina-Olsson, Ludmila Purdue, Mark Qiao, You-Lin Rabe, Kari G. Rajaraman, Preetha Real, Francisco X. Riboli, Elio Rodriguez-Santiago, Benjamin Rothman, Nathaniel Ruder, Avima M. Savage, Sharon A. Schwartz, Ann G. Schwartz, Kendra L. Sesso, Howard D. Severi, Gianluca 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. Viswanathan, Kala Wacholder, Sholom Wang, Zhaoming Weinstein, Stephanie J. Wheeler, William White, Emily Wiencke, John K. Wolpin, Brian M. Wu, Xifeng Wunder, Jay S. Yu, Kai Zanetti, Krista A. Zeleniuch-Jacquotte, Anne Ziegler, Regina G. De Andrade, Mariza Barnes, Kathleen C. Beaty, Terri H. Bierut, Laura J. Desch, Karl C. Doheny, Kimberly F. Feenstra, Bjarke Ginsburg, David Heit, John A. Kang, Jae H. Laurie, Cecilia A. Li, Jun Z. Lowe, William L. Marazita, Mary L. Melbye, Mads Mirel, Daniel B. Murray, Jeffrey C. Nelson, Sarah C. Pasquale, Louis R. Rice, Kenneth Wiggs, Janey L. Wise, Anastasia Tucker, Margaret Perez-Jurado, Luis A. Laurie, Cathy C. Caporaso, Neil E. Yeager, Meredith Chanock, Stephen J. TI Characterization of Large Structural Genetic Mosaicism in Human Autosomes SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DETECTABLE CLONAL MOSAICISM; COPY-NUMBER-VARIATION; SOMATIC MOSAICISM; MAFFUCCI SYNDROME; OLLIER DISEASE; HUMAN GENOME; MUTATIONS; CANCER; CELLS; IDENTIFICATION AB Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population. C1 [Machiela, Mitchell J.; Zhou, Weiyin; Sampson, Joshua N.; Black, Amanda; Brinton, Louise A.; Hartge, Patricia; Hosgood, H. Dean, III; Hu, Wei; Jessop, Lea; Lan, Qing; Wentzensen, Nicolas; Yang, Hannah P.; Abnet, Christian C.; Albanes, Demetrius; Amundadottir, Laufey T.; Berndt, Sonja I.; Burdett, Laurie; Chatterjee, Nilanjan; Chung, Charles C.; Cook, Michael B.; Cullen, Michael; Epstein, Caroline G.; Figueroa, Jonine D.; Fraumeni, Joseph F., Jr.; Freedman, Neal D.; Goldin, Lynn; Goldstein, Alisa M.; Greene, Mark H.; Hoover, Robert N.; Hu, Nan; Hutchinson, Amy; Landgren, Annelie; Landi, Maria Teresa; Liao, Linda M.; McGlynn, Katherine A.; Mirabello, Lisa; Prokunina-Olsson, Ludmila; Purdue, Mark; Rajaraman, Preetha; Rothman, Nathaniel; Savage, Sharon A.; Silverman, Debra T.; Stolzenberg-Solomon, Rachael; Taylor, Philip R.; Tobias, Geoffrey S.; Wacholder, Sholom; Wang, Zhaoming; Weinstein, Stephanie J.; Yu, Kai; Ziegler, Regina G.; Tucker, Margaret; Caporaso, Neil E.; Yeager, Meredith; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Zhou, Weiyin; Jacobs, Kevin B.; Burdett, Laurie; Chung, Charles C.; Cullen, Michael; Hutchinson, Amy; Wang, Zhaoming; Yeager, Meredith] NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, NIH,Leidos Biomed Res Inc, Bethesda, MD 20892 USA. [Dean, Michael C.] NCI, Expt Immunol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Jacobs, Kevin B.] BioInformed LLC, Gaithersburg, MD 20877 USA. [Chang, I-Shou] Natl Inst Canc Res, Natl Hlth Res Inst, 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; Hankinson, Susan E.; Hunter, David J.; Prescott, Jennifer; Fuchs, Charles S.; Giovannucci, Edward L.; Wolpin, Brian M.; Kang, Jae H.; Pasquale, Louis R.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Bou, Marta Crous; De Vivo, Immaculata; Hankinson, Susan E.; Hunter, David J.; Prescott, Jennifer; Fuchs, Charles S.; Gaziano, J. Michael; Giovannucci, Edward L.; Wolpin, Brian M.; Kang, Jae H.; Pasquale, Louis R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Doherty, Jennifer] Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA. [Friedenreich, Christine M.] Alberta Hlth Serv, CancerControl Alberta, Dept Populat Hlth Res, Calgary, AB T2N 2T9, Canada. [Gaudet, Mia M.; Gapstur, Susan M.; Stevens, Victoria L.; Teras, Lauren R.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA. [Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Setiawan, Veronica Wendy; VanDen Berg, David; Stram, Daniel] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Hankinson, Susan E.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA. [Hong, Yun-Chul] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 151742, South Korea. [Hosgood, H. Dean, III] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Hsiung, Chao A.] Inst Populat Hlth Sci, Natl Hlth Res Inst, Zhunan 35053, Taiwan. [Hunter, David J.; Mirel, Daniel B.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Kim, Hee Nam] Chonnam Natl Univ, Ctr Creat Biomed Scientists, Kwangju 500757, South Korea. [Kim, Yeul Hong] Korea Univ, Anam Hosp, Coll Med, Div Oncol Hematol,Dept Internal Med, Seoul 151742, South Korea. [Kim, Young Tae] Seoul Natl Univ, Coll Med, Dept Thorac & Cardiovasc Surg, Canc Res Inst, Seoul 151742, South Korea. [Klein, Robert] Mem Sloan Kettering Canc Ctr, Program Canc Biol & Genet, 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. [Le Marchand, Loic; Kolonel, Laurence N.] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96813 USA. [Liang, Xiaolin; Olson, Sara H.; Orlow, Irene; Rastogi, Radhai] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. [Lissowska, Jolanta] Maria Sklodowska Curie Canc Ctr, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, PL-02781 Warsaw, Poland. [Lu, Lingeng; Risch, Harvey A.] Yale Univ, Sch Publ Hlth, New Haven, CT 06510 USA. [Magliocco, Anthony M.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Matsuo, Keitaro] Kyushu Univ, Fac Med Sci, Dept Prevent Med, Fukuoka 8190395, Japan. [Park, Jae Yong] Kyungpook Natl Univ, Med Ctr, Lung Canc Ctr, Daegu 101, South Korea. [Pooler, Loreall; Sheng, Xin; Xia, Lucy] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90007 USA. [Seow, Adeline; Koh, Woon-Puay] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 119077, Singapore. [Shen, Hongbing] Nanjing Med Univ, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing 210029, Jiangsu, Peoples R China. [Shen, Hongbing] Nanjing Med Univ, Minist Educ, Key Lab Modern Toxicol, 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, Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37232 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. [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, Minist Educ, Key Lab Environm & Hlth, Wuhan 430400, Peoples R China. [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. [Yang, Pan-Chyr] Natl Taiwan Univ, Dept Internal Med, Coll Med, Taipei 10617, Taiwan. [Zheng, Wei; Aldrich, Melinda C.; Blot, William J.] Vanderbilt Univ, Med Ctr, Vanderbilt Epidemiol Ctr, Div Epidemiol,Dept Med, Nashville, TN 37232 USA. [Zhou, Baosen] China Med Univ, Sch Publ Hlth, Dept Epidemiol, Shenyang 110001, Peoples R China. [Aldrich, Melinda C.] Vanderbilt Univ, Sch Med, Dept Thorac Surg, Nashville, TN 37232 USA. [Amos, Christopher] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Div Canc Prevent & Populat Sci, Houston, TX 77030 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. [Buring, Julie E.; Sesso, Howard D.] 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. [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. [Duell, Eric J.] Catalan Inst Oncol, Bellvitge Biomed Res Inst, Canc Epidemiol Res Program, Unit Nutr Environm & Canc, Barcelona 08908, Spain. [Fan, Jin-Hu] Shanghai Canc Inst, Shanghai 200032, Peoples R China. [Fuchs, Charles S.; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Gao, Yu-Tang] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Epidemiol,Shanghai Canc Inst, Shanghai 200032, Peoples R China. [Patino-Garcia, Ana] Univ Navarra, Univ Navarra Clin, Dept Pediat, E-31080 Pamplona, Spain. [Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, London SM2 5NG, Surrey, England. [Garcia-Closas, Montserrat] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London 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] Vet Affairs Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02130 USA. [Gaziano, J. Michael] Vet Affairs Boston Healthcare Syst, Cooperat Studies Programs, Boston, MA 02130 USA. [Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Canc Council Victoria, Canc Epidemiol Ctr, 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, NIH, Bethesda, MD 20892 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med, Nutr Res Unit, S-90187 Umea, Sweden. [Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Henriksson, Roger; Melin, Beatrice S.] Umea Univ, Dept Radiat Sci, Dept Oncol, S-90187 Umea, Sweden. [Jenab, Mazda] Int Agcy Res Canc, F-69372 Lyon, France. [Johansen, Christoffer] Rigshosp, Finsen Ctr, Dept 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. [Koh, Woon-Puay] Duke NUS Grad Med Sch, Singapore 169857, Singapore. [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. [Malats, Nuria; Real, Francisco X.] Spanish Natl Canc Res Ctr, Madrid 28029, Spain. [McNeill, Lorna H.] Univ Texas MD Anderson Canc Ctr, Dept Hlth Dispar Res, Div OVP Canc Prevent & Populat Sci, Houston, TX 77030 USA. [McNeill, Lorna H.] Univ Texas MD Anderson Canc Ctr, Ctr Community Engaged Translat Res, Duncan Family Inst, Houston, TX 77030 USA. [McWilliams, Robert R.] Mayo Clin, Dept Oncol, Rochester, MN 55905 USA. [Peplonska, Beata] Nofer Inst Occupat Med, PL-91348 Lodz, Poland. [Petersen, Gloria M.; Rabe, Kari G.; De Andrade, Mariza] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Qiao, You-Lin] Chinese Acad Med Sci, Inst Canc, 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 08003, 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, Barcelona 08003, 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, I-10126 Turin, Italy. [Spitz, Margaret R.] Baylor Coll Med, Houston, TX 77030 USA. [Viswanathan, Kala; Beaty, Terri H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. [Wheeler, William] Informat Management Serv Inc, Calverton, MD 20904 USA. [Wiencke, John K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Wunder, Jay S.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. [Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Populat Hlth, New York, NY 10016 USA. [Zeleniuch-Jacquotte, Anne] NYU, Perlmutter Canc Inst, New York, NY 10016 USA. [Barnes, Kathleen C.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. [Bierut, Laura J.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Desch, Karl C.] Univ Michigan, Dept Pediat & Communicable Dis, CS Mott Childrens Hosp, Ann Arbor, MI 48109 USA. [Doheny, Kimberly F.] Johns Hopkins Univ, Inst Med Genet, Sch Med, Ctr Inherited Dis Res, Baltimore, MD 21218 USA. [Feenstra, Bjarke; Melbye, Mads] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Ginsburg, David] Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA. [Ginsburg, David] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Heit, John A.] Mayo Clin, Dept Internal Med, Rochester, MN 55905 USA. [Laurie, Cecilia A.; Nelson, Sarah C.; Rice, Kenneth; Laurie, Cathy C.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Li, Jun Z.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Lowe, William L.] Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Evanston, IL 60208 USA. [Marazita, Mary L.] Univ Pittsburgh, Sch Dent Med, Dept Oral Biol, Ctr Craniofacial & Dent Genet, Pittsburgh, PA 15260 USA. [Marazita, Mary L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15260 USA. [Melbye, Mads] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Pasquale, Louis R.; Wiggs, Janey L.] Harvard Univ, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Wise, Anastasia] NHGRI, Off Populat Genom, NIH, Bethesda, MD 20892 USA. [Perez-Jurado, Luis A.] Hosp del Mar, Res Inst, Barcelona 08003, Spain. RP Chanock, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM chanocks@mail.nih.gov RI Hsiung, Chao Agnes/E-3994-2010; Garcia-Closas, Montserrat /F-3871-2015; Chang, I-Shou/D-2084-2010; Brinton, Louise/G-7486-2015; Freedman, Neal/B-9741-2015; Abnet, Christian/C-4111-2015; Malats, Nuria/H-7041-2015; Patino-Garcia, Ana/I-4299-2012; Perez Jurado, Luis Alberto/M-7706-2015; Real Arribas, Francisco/H-5275-2015; Cook, Michael/A-5641-2009; U-ID, Kyushu/C-5291-2016; Savage, Sharon/B-9747-2015; Krogh, Vittorio/K-2628-2016; Tobias, Geoffrey/M-4135-2016; Qiao, You-Lin/B-4139-2012; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Freedman, Neal/0000-0003-0074-1098; Abnet, Christian/0000-0002-3008-7843; Malats, Nuria/0000-0003-2538-3784; Real Arribas, Francisco/0000-0001-9501-498X; Cook, Michael/0000-0002-0533-7302; Savage, Sharon/0000-0001-6006-0740; Krogh, Vittorio/0000-0003-0122-8624; Tobias, Geoffrey/0000-0002-2878-8253; Qiao, You-Lin/0000-0001-6380-0871; Nelson, Sarah/0000-0002-2109-6465; Rodriguez-Santiago, Benjamin/0000-0003-1167-3852; YANG, PAN-CHYR/0000-0001-6330-6048; Prokunina-Olsson, Ludmila/0000-0002-9622-2091; Liao, Linda/0000-0002-1923-5294; Machiela, Mitchell/0000-0001-6538-9705; Orlow, Irene/0000-0001-6234-6961; Giles, Graham/0000-0003-4946-9099; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303; Matsuo, Keitaro/0000-0003-1761-6314 FU Medical Research Council [G0401527, G1000143]; NCI NIH HHS [R25 CA174664, K05 CA154337, K07 CA172294, P01 CA087969, P30 CA008748, P30 CA016672, P30 CA023108, R01 CA092447, R01 CA124908, UM1 CA182934]; NEI NIH HHS [P30 EY014104, R01 EY015473, R01 EY022305]; NHLBI NIH HHS [R01 HL039693, R01 HL112642]; NIDCR NIH HHS [R01 DE014899, R01 DE016148] NR 35 TC 14 Z9 14 U1 2 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR 5 PY 2015 VL 96 IS 3 BP 487 EP 497 DI 10.1016/j.ajhg.2015.01.011 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA CD0GD UT WOS:000350747800022 PM 25748358 ER PT J AU Kfoury, Y Scadden, DT AF Kfoury, Youmna Scadden, David T. TI Mesenchymal Cell Contributions to the Stem Cell Niche SO CELL STEM CELL LA English DT Review ID HUMAN-BONE-MARROW; GROWTH-FACTOR RECEPTOR; HEMATOPOIETIC MICRO-ENVIRONMENT; THERAPY POSITION STATEMENT; COLONY-FORMING CELLS; LONG-TERM CULTURE; STROMAL CELLS; PROGENITOR CELLS; IN-VIVO; RADIATION SENSITIVITY AB Mesenchymal stromal cells (MSCs) are heterogeneous and primitive cells discovered first in the bone marrow (BM). They have putative roles in maintaining tissue homeostasis and are increasingly recognized as components of stem cell niches, which are best defined in the blood. The absence of in vivo MSC markers has limited our ability to track their behavior in vivo and draw comparisons with in vitro observations. Here we review the historical background of BM-MSCs, advances made in their prospective isolation, their developmental origin and contribution to maintaining subsets of hematopoietic cells, and how mesenchymal cells contribute to other stem cell niches. C1 [Kfoury, Youmna; Scadden, David T.] Harvard Univ, Ctr Regenerat Med, Boston, MA 02114 USA. [Kfoury, Youmna; Scadden, David T.] Harvard Univ, MGH Canc Ctr, Massachusetts Gen Hosp, Dept Stem Cell & Regenerat Biol, Boston, MA 02114 USA. [Kfoury, Youmna; Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02114 USA. RP Scadden, DT (reprint author), Harvard Univ, Ctr Regenerat Med, Boston, MA 02114 USA. EM david_scadden@harvard.edu FU National Institutes of Health [U01H100402, R01EB014703, R01HL044851]; Aplastic Anemia and MDS International foundation; Dubai Harvard foundation FX D.T.S. is Gerald and Darlene Jordan Professor of Medicine and was supported by the National Institutes of Health (U01H100402, R01EB014703, and R01HL044851). Y.K. is a recipient of the Aplastic Anemia and MDS International foundation research grant and a former recipient of the Dubai Harvard foundation for medical research post-doctoral fellowship. NR 140 TC 56 Z9 59 U1 10 U2 55 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 MAR 5 PY 2015 VL 16 IS 3 BP 239 EP 253 DI 10.1016/j.stem.2015.02.019 PG 15 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA CD0GC UT WOS:000350747700007 PM 25748931 ER PT J AU Hallett, PJ Deleidi, M Astradsson, A Smith, GA Cooper, O Osborn, TM Sundberg, M Moore, MA Perez-Torres, E Brownell, AL Schumacher, JM Spealman, RD Isacson, O AF Hallett, Penelope J. Deleidi, Michela Astradsson, Arnar Smith, Gaynor A. Cooper, Oliver Osborn, Teresia M. Sundberg, Maria Moore, Michele A. Perez-Torres, Eduardo Brownell, Anna-Liisa Schumacher, James M. Spealman, Roger D. Isacson, Ole TI Successful Function of Autologous iPSC-Derived Dopamine Neurons following Transplantation in a Non-Human Primate Model of Parkinson's Disease SO CELL STEM CELL LA English DT Article ID PLURIPOTENT STEM-CELLS; RAT MODEL; VENTRAL MESENCEPHALON; NEURAL CELLS; C-11 CFT; IN-VIVO; BRAIN; DIFFERENTIATION; DEFICIENT; SYMPTOMS AB Autologous transplantation of patient-specific induced pluripotent stem cell (iPSC)-derived neurons is a potential clinical approach for treatment of neurological disease. Preclinical demonstration of long-term efficacy, feasibility, and safety of iPSC-derived dopamine neurons in non-human primate models will be an important step in clinical development of cell therapy. Here, we analyzed cynomolgus monkey (CM) iPSC-derived midbrain dopamine neurons for up to 2 years following autologous transplantation in a Parkinson's disease (PD) model. In one animal, with the most successful protocol, we found that unilateral engraftment of CM-iPSCs could provide a gradual onset of functional motor improvement contralateral to the side of dopamine neuron transplantation, and increased motor activity, without a need for immunosuppression. Postmortem analyses demonstrated robust survival of midbrain-like dopaminergic neurons and extensive outgrowth into the transplanted putamen. Our proof of concept findings support further development of autologous iPSC-derived cell transplantation for treatment of PD. C1 [Hallett, Penelope J.; Deleidi, Michela; Astradsson, Arnar; Smith, Gaynor A.; Cooper, Oliver; Osborn, Teresia M.; Sundberg, Maria; Moore, Michele A.; Perez-Torres, Eduardo; Brownell, Anna-Liisa; Schumacher, James M.; Spealman, Roger D.; Isacson, Ole] McLean Hosp, Neuroregenerat Res Inst, Belmont, MA 02478 USA. [Hallett, Penelope J.; Deleidi, Michela; Astradsson, Arnar; Smith, Gaynor A.; Cooper, Oliver; Osborn, Teresia M.; Sundberg, Maria; Moore, Michele A.; Perez-Torres, Eduardo; Brownell, Anna-Liisa; Schumacher, James M.; Spealman, Roger D.; Isacson, Ole] Harvard Univ, Sch Med, Belmont, MA 02478 USA. [Moore, Michele A.; Spealman, Roger D.] Harvard Univ, Sch Med, New England Primate Res Ctr, Southborough, MA 01772 USA. [Brownell, Anna-Liisa] Massachusetts Gen Hosp, MGH HST Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Brownell, Anna-Liisa] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Isacson, Ole] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Isacson, O (reprint author), McLean Hosp, Neuroregenerat Res Inst, Belmont, MA 02478 USA. EM isacson@hms.harvard.edu OI Cooper, Oliver/0000-0001-6567-7491; Hallett, Penelope/0000-0002-8858-9096 FU Harvard Stem Cell Institute Miller Consortium; Udall Parkinson's Disease Center of Excellence [P50 NS39793]; Department of Defense [WX81XWH-11-1-0069]; Orchard Foundation; Poul Hansen Family; Consolidated Anti-Aging Foundation; Harold and Ronna Cooper Family; National Center for Research Resources [RR00168]; Office of Research Infrastructure Programs [OD011103] FX We thank the veterinary and research staff, including Dr. Leah Makaron, Dr. Angela Carville, Dr. Andrew Miller, Matthew Beck, Jack McDowell, Melissa Hayes, Jonathan Beagan, Zachary Schneider-Lynch, Sayantan Deb, and Alex Casler, at the New England Primate Research Center and the Neuroregeneration Research Institute for excellent veterinary and technical assistance. This study was supported by the Harvard Stem Cell Institute Miller Consortium for the Development of Nervous System Therapies and the Udall Parkinson's Disease Center of Excellence grant P50 NS39793, Department of Defense WX81XWH-11-1-0069, Orchard Foundation, Poul Hansen Family, Consolidated Anti-Aging Foundation and Harold and Ronna Cooper Family (to O.I.), National Center for Research Resources RR00168, and the Office of Research Infrastructure Programs OD011103 (to R.D.S.). NR 28 TC 45 Z9 48 U1 4 U2 43 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 MAR 5 PY 2015 VL 16 IS 3 BP 269 EP 274 DI 10.1016/j.stem.2015.01.018 PG 6 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA CD0GC UT WOS:000350747700009 PM 25732245 ER PT J AU Ewald, CY Landis, JN Abate, JP Murphy, CT Blackwell, TK AF Ewald, Collin Y. Landis, Jess N. Abate, Jess Porter Murphy, Coleen T. Blackwell, T. Keith TI Dauer-independent insulin/IGF-1-signalling implicates collagen remodelling in longevity SO NATURE LA English DT Article ID ELEGANS LIFE-SPAN; NEMATODE CAENORHABDITIS-ELEGANS; LARGE GENE LISTS; C-ELEGANS; STRESS-RESPONSE; REGULATES LONGEVITY; PROLINE CATABOLISM; MESSENGER-RNA; EXPRESSION; DAF-2 AB Interventions that delay ageing mobilize mechanisms that protect and repair cellular components(1-3), but it is unknown how these interventions might slow the functional decline of extracellular matrices(4,5), which are also damaged during ageing(6,7). Reduced insulin/I GF-1 signalling (HIS) extends lifespan across the evolutionary spectrum, and in juvenile Caenorhabditis elegans also allows the transcription factor DAF-16/FOX0 to induce development into dauer, a diapause that withstands harsh conditions(1,2). It has been suggested that rIIS delays C. elegans ageing through activation of dauer-related processes during adulthood(2,8,9), but some HIS conditions confer robust lifespan extension unaccompanied by any dauer-like traits(1,10,11). Here we show that HIS can promote C. elegans longevity through a program that is genetically distinct from the dauer pathway, and requires the Nrf (NF-E2-related factor) orthologue SKN-1 acting in parallel to DAF-16. SKN-1 is inhibited by IIS and has been broadly implicated in longevity(12-14), but is rendered dispensable for HIS lifespan extension by even mild activity of dauer-related processes. When IIS is decreased under conditions that do not induce dauer traits, SKN-1 most prominently increases expression of collagens and other extracellular matrix genes. Diverse genetic, nutritional, and pharmacological pro-longevity interventions delay an age-related decline in collagen expression. These collagens mediate adulthood extracellular matrix remodelling, and are needed for ageing to be delayed by interventions that do not involve dauer traits. By genetically delineating a dauer-independent HIS ageing pathway, our results show that IIS controls a broad set of protective mechanisms during C. elegans adulthood, and may facilitate elucidation of processes of general importance for longevity. The importance of collagen production in diverse anti-ageing interventions implies that extracellular matrix remodelling is a generally essential signature of longevity assurance, and that agents promoting extracellular matrix youthfulness may have systemic benefit. C1 [Ewald, Collin Y.; Abate, Jess Porter; Blackwell, T. Keith] Joslin Diabet Ctr, Boston, MA 02215 USA. [Ewald, Collin Y.; Abate, Jess Porter; Blackwell, T. Keith] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Ewald, Collin Y.; Abate, Jess Porter; Blackwell, T. Keith] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA. [Landis, Jess N.; Murphy, Coleen T.] Princeton Univ, Dept Mol Biol, Lewis Sigler Inst Integrat Genom, Carl Icahn Lab 148, Princeton, NJ 08544 USA. RP Blackwell, TK (reprint author), Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02215 USA. EM ctmurphy@princeton.edu; keith.blackwell@joslin.harvard.edu RI Ewald, Collin/K-6303-2015 OI Ewald, Collin/0000-0003-1166-4171 FU National Institutes of Health Office of Research Infrastructure Programs [P40 OD010440]; National Institutes of Health [GM062891, 5T32DK007260]; Diabetes Research Center award [P30DK036836]; National Science Foundation; Swiss National Science Foundation [PBSKP3_140135] FX We thank C. Kenyon,S. Mitani, and J. Shim for strains, P. Sengupta fordauer pheromone, C. Obieglo, L. Moronetti, M. Bland,and K. Patel for assistance,and J. Apfeld, E. Greer, C. Kenyon, W. Mair, and Blackwell laboratory members for discussions or comments on the manuscript. Some strains were provided by the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health Office of Research Infrastructure Programs (P40 OD010440). The work was supported by funding from the National Institutes of Health to T.K.B. (GM062891), C.T.M. (New Innovator), and J.P.A. (5T32DK007260), a Diabetes Research Center award to the Joslin Diabetes Center (P30DK036836), and fellowships from the National Science Foundation to J.N.L., and the Swiss National Science Foundation (PBSKP3_140135) to C.Y.E. NR 93 TC 37 Z9 37 U1 4 U2 55 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 MAR 5 PY 2015 VL 519 IS 7541 BP 97 EP U212 DI 10.1038/nature14021 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CC4EQ UT WOS:000350304000043 PM 25517099 ER PT J AU Moore, HCF Unger, JM Phillips, KA Boyle, F Hitre, E Porter, D Francis, PA Goldstein, LJ Gomez, HL Vallejos, CS Partridge, AH Dakhil, SR Garcia, AA Gralow, J Lombard, JM Forbes, JF Martino, S Barlow, WE Fabian, CJ Minasian, L Meyskens, FL Gelber, RD Hortobagyi, GN Albain, KS AF Moore, Halle C. F. Unger, Joseph M. Phillips, Kelly-Anne Boyle, Frances Hitre, Erika Porter, David Francis, Prudence A. Goldstein, Lori J. Gomez, Henry L. Vallejos, Carlos S. Partridge, Ann H. Dakhil, Shaker R. Garcia, Agustin A. Gralow, Julie Lombard, Janine M. Forbes, John F. Martino, Silvana Barlow, William E. Fabian, Carol J. Minasian, Lori Meyskens, Frank L., Jr. Gelber, Richard D. Hortobagyi, Gabriel N. Albain, Kathy S. CA POEMS S0230 Investigators TI Goserelin for Ovarian Protection during Breast-Cancer Adjuvant Chemotherapy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED-CONTROLLED-TRIAL; FERTILITY PRESERVATION; HORMONE AGONISTS; SUPPRESSION; AMENORRHEA; WOMEN; TRIPTORELIN; PREVENTION AB BACKGROUND Ovarian failure is a common toxic effect of chemotherapy. Studies of the use of gonadotropin-releasing hormone (GnRH) agonists to protect ovarian function have shown mixed results and lack data on pregnancy outcomes. METHODS We randomly assigned 257 premenopausal women with operable hormone-receptor-negative breast cancer to receive standard chemotherapy with the GnRH agonist goserelin (goserelin group) or standard chemotherapy without goserelin (chemotherapy-alone group). The primary study end point was the rate of ovarian failure at 2 years, with ovarian failure defined as the absence of menses in the preceding 6 months and levels of follicle-stimulating hormone (FSH) in the postmenopausal range. Rates were compared with the use of conditional logistic regression. Secondary end points included pregnancy outcomes and disease-free and overall survival. RESULTS At baseline, 218 patients were eligible and could be evaluated. Among 135 with complete primary end-point data, the ovarian failure rate was 8% in the goserelin group and 22% in the chemotherapy-alone group (odds ratio, 0.30; 95% confidence interval, 0.09 to 0.97; two-sided P = 0.04). Owing to missing primary end-point data, sensitivity analyses were performed, and the results were consistent with the main findings. Missing data did not differ according to treatment group or according to the stratification factors of age and planned chemotherapy regimen. Among the 218 patients who could be evaluated, pregnancy occurred in more women in the goserelin group than in the chemotherapy-alone group (21% vs. 11%, P = 0.03); women in the goserelin group also had improved disease-free survival (P = 0.04) and overall survival (P = 0.05). CONCLUSIONS Although missing data weaken interpretation of the findings, administration of goserelin with chemotherapy appeared to protect against ovarian failure, reducing the risk of early menopause and improving prospects for fertility. (Funded by the National Cancer Institute and others; POEMS/S0230 ClinicalTrials.gov number, NCT00068601.) C1 [Moore, Halle C. F.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Unger, Joseph M.; Barlow, William E.] Fred Hutchinson Canc Res Ctr, SWOG Canc Res Grp Stat Ctr, Seattle, WA 98104 USA. [Gralow, Julie] Seattle Canc Care Alliance, Seattle, WA USA. [Gralow, Julie] Univ Washington, Seattle, WA 98195 USA. [Phillips, Kelly-Anne; Francis, Prudence A.] Univ Melbourne, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Phillips, Kelly-Anne; Francis, Prudence A.; Forbes, John F.] New Zealand Breast Canc Trials Grp ANZBCTG, Newcastle, NSW, Australia. [Boyle, Frances; Lombard, Janine M.; Forbes, John F.] Calvary Mater Hosp, Newcastle, NSW, Australia. [Boyle, Frances] Univ Sydney, Sydney, NSW 2006, Australia. [Phillips, Kelly-Anne; Francis, Prudence A.] IBCSG, Bern, Switzerland. [Hitre, Erika] Natl Inst Oncol, Budapest, Hungary. [Porter, David] Auckland Reg Canc & Blood Serv, Auckland, New Zealand. [Goldstein, Lori J.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Gomez, Henry L.] Inst Enfermedades Neoplas, Lima, Peru. [Vallejos, Carlos S.] Oncosalud SAC, Lima, Peru. [Partridge, Ann H.; Gelber, Richard D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gelber, Richard D.] IBCSG Stat Ctr, Boston, MA USA. [Dakhil, Shaker R.] Wichita Community Clin Oncol Program, Wichita, KS USA. [Fabian, Carol J.] Univ Kansas, Westwood, KS USA. [Garcia, Agustin A.] Univ So Calif, Norris Canc Ctr, Los Angeles, CA USA. [Martino, Silvana] Angeles Clin, Santa Monica, CA USA. [Martino, Silvana] Res Inst, Santa Monica, CA USA. [Meyskens, Frank L., Jr.] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Orange, CA 92668 USA. [Minasian, Lori] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Hortobagyi, Gabriel N.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Albain, Kathy S.] Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. RP Moore, HCF (reprint author), Cleveland Clin Fdn, Taussig Canc Inst, R35,9500 Euclid Ave, Cleveland, OH 44195 USA. EM mooreh1@ccf.org OI Gomez, Henry/0000-0003-2660-1843; Phillips, Kelly-Anne/0000-0002-0475-1771 FU National Cancer Institute FX Funded by the National Cancer Institute and others; POEMS/S0230 ClinicalTrials.gov number, NCT00068601. NR 23 TC 102 Z9 108 U1 3 U2 30 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 MAR 5 PY 2015 VL 372 IS 10 BP 923 EP 932 DI 10.1056/NEJMoa1413204 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CC4EU UT WOS:000350304500008 PM 25738668 ER PT J AU Simmons, LH Iyasere, CA Hamilton, KL AF Simmons, Leigh H. Iyasere, Christiana A. Hamilton, Kathleen L. TI Case 38-2014: A Man with Sore Throat, Hoarseness, Fatigue, and Dyspnea REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Simmons, Leigh H.; Iyasere, Christiana A.; Hamilton, Kathleen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Simmons, LH (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 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 MAR 5 PY 2015 VL 372 IS 10 BP 982 EP 982 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CC4EU UT WOS:000350304500025 PM 25738684 ER PT J AU Lyons, KD Hull, JG Kaufman, PA Li, ZZ Seville, JL Ahles, TA Kornblith, AB Hegel, MT AF Lyons, Kathleen D. Hull, Jay G. Kaufman, Peter A. Li, Zhongze Seville, Janette L. Ahles, Tim A. Kornblith, Alice B. Hegel, Mark T. TI Development and Initial Evaluation of a Telephone-Delivered, Behavioral Activation, and Problem-Solving Treatment Program to Address Functional Goals of Breast Cancer Survivors SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article DE survivorship; occupational therapy; rehabilitation ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; PARTICIPATION RESTRICTIONS; PHYSICAL PERFORMANCE; RADIATION-THERAPY; DEPRESSION; SCALE; INTERVENTION; METAANALYSIS; RELIABILITY AB The purpose of this research was to develop and pilot test an intervention to optimize functional recovery for breast cancer survivors. Over two studies, 31 women enrolled in a goal-setting program via telephone. All eligible women enrolled (37% of those screened) and 66% completed all study activities. Completers were highly satisfied with the intervention, using it to address, on average, four different challenging activities. The longitudinal analysis showed a main effect of time for overall quality of life (F(5, 43.1) = 5.1, p = 0.001) and improvements in active coping (F (3, 31.7) = 4.9, p = 0.007), planning (F (3, 36.0) = 4.1, p = 0.01), reframing (F (3, 29.3) = 8.5, p < 0.001), and decreases in self-blame (F (3,31.6) = 4.3, p = 0.01). The intervention is feasible and warrants further study to determine its efficacy in fostering recovery and maximizing activity engagement after cancer treatment. C1 [Lyons, Kathleen D.; Kaufman, Peter A.; Seville, Janette L.; Hegel, Mark T.] Dartmouth Coll, Geisel Sch Med Dartmouth, Hanover, NH 03755 USA. [Lyons, Kathleen D.; Hegel, Mark T.] Norris Cotton Canc Ctr, Canc Control Program, Lebanon, NH USA. [Hull, Jay G.] Dartmouth Coll, Dartmouth Grad Studies, Hanover, NH 03755 USA. [Kaufman, Peter A.] Norris Cotton Canc Ctr, Mol Therapeut Program, Lebanon, NH USA. [Li, Zhongze] Norris Cotton Canc Ctr, Biostat Shared Resource, Lebanon, NH USA. [Ahles, Tim A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Kornblith, Alice B.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lyons, KD (reprint author), Dartmouth Hitchcock Med Ctr, Psychiat Dept 7750, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM kathleen.d.lyons@dartmouth.edu FU Alliance for Clinical Trials in Oncology Foundation [70804]; National Cancer Institute [R21 CA140849-01]; Mentored Research Scholar Grant in Applied and Clinical Research from the American Cancer Society [MRSG-12-113-01-CPPB] FX These studies were funded by grants to Dr. Hegel from the Cancer and Leukemia Group B Foundation (now the Alliance for Clinical Trials in Oncology Foundation; #70804; Study 1) and the National Cancer Institute (1 R21 CA140849-01; Study 2). The first author was supported by a Mentored Research Scholar Grant in Applied and Clinical Research, MRSG-12-113-01-CPPB from the American Cancer Society. NR 29 TC 2 Z9 2 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0734-7332 EI 1540-7586 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PD MAR 4 PY 2015 VL 33 IS 2 BP 199 EP 218 DI 10.1080/07347332.2014.1002659 PG 20 WC Psychology, Social SC Psychology GA CG6NC UT WOS:000353417400006 PM 25668509 ER PT J AU Yao, YW Cui, XT Al-Ramahi, I Sun, XL Li, B Hou, JP Difiglia, M Palacino, J Wu, ZY Ma, LX Botas, J Lu, BX AF Yao, Yuwei Cui, Xiaotian Al-Ramahi, Ismael Sun, Xiaoli Li, Bo Hou, Jiapeng Difiglia, Marian Palacino, James Wu, Zhi-Ying Ma, Lixiang Botas, Juan Lu, Boxun TI A striatal-enriched intronic GPCR modulates huntingtin levels and toxicity SO ELIFE LA English DT Article ID DEPENDENT PROTEIN-KINASE; LONG NONCODING RNAS; MUTANT-HUNTINGTIN; CYCLIC-AMP; HUMAN BRAIN; DISEASE; CAMP; NEURONS; EPAC; MICE AB Huntington's disease (HD) represents an important model for neurodegenerative disorders and proteinopathies. It is mainly caused by cytotoxicity of the mutant huntingtin protein (Htt) with an expanded polyQ stretch. While Htt is ubiquitously expressed, HD is characterized by selective neurodegeneration of the striatum. Here we report a striatal-enriched orphan G proteincoupled receptor(GPCR) Gpr52 as a stabilizer of Htt in vitro and in vivo. Gpr52 modulates Htt via cAMP-dependent but PKA independent mechanisms. Gpr52 is located within an intron of Rabgap1l, which exhibits epistatic effects on Gpr52-mediated modulation of Htt levels by inhibiting its substrate Rab39B, which co-localizes with Htt and translocates Htt to the endoplasmic reticulum. Finally, reducing Gpr52 suppresses HD phenotypes in both patient iPS-derived neurons and in vivo Drosophila HD models. Thus, our discovery reveals modulation of Htt levels by a striatal-enriched GPCR via its GPCR function, providing insights into the selective neurodegeneration and potential treatment strategies. C1 [Yao, Yuwei; Cui, Xiaotian; Sun, Xiaoli; Li, Bo; Hou, Jiapeng; Lu, Boxun] Fudan Univ, Sch Life Sci, Dept Biophys, State Key Lab Genet Engn, Shanghai 200433, Peoples R China. [Yao, Yuwei; Cui, Xiaotian; Sun, Xiaoli; Lu, Boxun] Collaborat Innovat Ctr Brain Sci, Shanghai, Peoples R China. [Al-Ramahi, Ismael; Botas, Juan] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Difiglia, Marian] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Boston, MA 02114 USA. [Palacino, James] Novartis Inst Biomed Res, Dev Mol Pathways, Cambridge, MA USA. [Wu, Zhi-Ying] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Neurol, Hangzhou 310003, Zhejiang, Peoples R China. [Wu, Zhi-Ying] Zhejiang Univ, Affiliated Hosp 2, Res Ctr Neurol, Sch Med, Hangzhou 310003, Zhejiang, Peoples R China. [Ma, Lixiang] Fudan Univ, Shanghai Med Coll, Dept Anat Histol & Embryol, Shanghai 200433, Peoples R China. RP Wu, ZY (reprint author), Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Neurol, Hangzhou 310003, Zhejiang, Peoples R China. EM zhiyingwu@zju.edu.cn; lxma@fudan.edu.cn; jbotas@bcm.edu; luboxun@fudan.edu.cn RI Al-Ramahi, Ismael/B-4000-2017 OI Al-Ramahi, Ismael/0000-0002-1275-1114 FU National Natural Science Foundation of China (NSFC) [31371421, 31422024, 81271259, 12ZR1403100]; Ministry of Science and Technology of the People's Republic of China [2014AA02502]; Science and Technology Commission of Shanghai Municipality [13PJ1400600]; National Institutes of Health (NIH) [NS42179] FX National Natural Science Foundation of China (NSFC) 31371421 Yuwei Yao, Xiaotian Cui, Xiaoli Sun, Bo Li, Jiapeng Hou, Boxun Lu; National Natural Science Foundation of China (NSFC) 31422024 Yuwei Yao, Xiaotian Cui, Xiaoli Sun, Bo Li, Jiapeng Hou, Boxun Lu; Ministry of Science and Technology of the People's Republic of China 2014AA02502 Yuwei Yao, Xiaotian Cui, Xiaoli Sun, Boxun Lu; Science and Technology Commission of Shanghai Municipality 13PJ1400600 Boxun Lu; National Natural Science Foundation of China (NSFC) 81271259 Lixiang Ma; National Natural Science Foundation of China (NSFC) 12ZR1403100 Lixiang Ma; National Institutes of Health (NIH) NS42179 Ismael Al-Ramahi, Juan Botas NR 46 TC 5 Z9 5 U1 7 U2 16 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD MAR 4 PY 2015 VL 4 AR e05449 DI 10.7554/eLife.05449 PG 19 WC Biology SC Life Sciences & Biomedicine - Other Topics GA CE5IC UT WOS:000351863800001 ER PT J AU Menkes-Caspi, N Yamin, HG Kellner, V Spires-Jones, TL Cohen, D Stern, EA AF Menkes-Caspi, Noa Yamin, Hagar G. Kellner, Vered Spires-Jones, Tara L. Cohen, Dana Stern, Edward A. TI Pathological Tau Disrupts Ongoing Network Activity SO NEURON LA English DT Article ID RTG4510 MOUSE MODEL; NEURONS IN-VIVO; PYRAMIDAL CELLS; TAUOPATHY; INHIBITION; CORTEX; NEURODEGENERATION; OSCILLATION; VARIABILITY; INTEGRATION AB Pathological tau leads to dementia and neurodegeneration in tauopathies, including Alzheimer's disease. It has been shown to disrupt cellular and synaptic functions, yet its effects on the function of the intact neocortical network remain unknown. Using in vivo intracellular and extracellular recordings, we measured ongoing activity of neocortical pyramidal cells during various arousal states in the rTg4510 mouse model of tauopathy, prior to significant cell death, when only a fraction of the neurons show pathological tau. In transgenic mice, membrane potential oscillations are slower during slow-wave sleep and under anesthesia. Intracellular recordings revealed that these changes are due to longer Down states and state transitions of membrane potentials. Firing rates of transgenic neurons are reduced, and firing patterns within Up states are altered, with longer latencies and inter-spike intervals. By changing the activity patterns of a subpopulation of affected neurons, pathological tau reduces the activity of the neocortical network. C1 [Menkes-Caspi, Noa; Yamin, Hagar G.; Kellner, Vered; Cohen, Dana; Stern, Edward A.] Bar Ilan Univ, Gonda Brain Res Ctr, IL-52900 Ramat Gan, Israel. [Spires-Jones, Tara L.] Univ Edinburgh, Ctr Cognit & Neural Syst, Edinburgh EH8 9XD, Midlothian, Scotland. [Spires-Jones, Tara L.] Univ Edinburgh, Euan MacDonald Ctr Motorneurone Dis Res, Edinburgh EH8 9XD, Midlothian, Scotland. [Stern, Edward A.] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP Stern, EA (reprint author), Bar Ilan Univ, Gonda Brain Res Ctr, IL-52900 Ramat Gan, Israel. EM sterned@mail.biu.ac.il FU Alzheimer's Research UK FX We are grateful to Dr. Jada Lewis for granting permission to use the rTg4510 mice; and to Professor George Carlson and Ms. Rose Pitstick for kindly providing them. We thank Dr. Peter Davies for kindly providing PHF1 and Alz50 antibodies, and Dr. Shih-Chieh Lin for kindly providing the MATLAB code for construction of a two-dimensional state space. We thank Professors Bradley T. Hyman and Israel Nelken for critical reading of the manuscript. Funding for this work was provided by Alzheimer's Research UK (T.S.-J.). NR 29 TC 14 Z9 14 U1 3 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD MAR 4 PY 2015 VL 85 IS 5 BP 959 EP 966 DI 10.1016/j.neuron.2015.01.025 PG 8 WC Neurosciences SC Neurosciences & Neurology GA CD8AZ UT WOS:000351318900010 PM 25704951 ER PT J AU Xia, D Watanabe, H Wu, B Lee, SH Li, Y Tsvetkov, E Bolshakov, VY Shen, J Kelleher, RJ AF Xia, Dan Watanabe, Hirotaka Wu, Bei Lee, Sang Hun Li, Yan Tsvetkov, Evgeny Bolshakov, Vadim Y. Shen, Jie Kelleher, Raymond J., III TI Presenilin-1 Knockin Mice Reveal Loss-of-Function Mechanism for Familial Alzheimer's Disease SO NEURON LA English DT Article ID AMYLOID PRECURSOR PROTEIN; GAMMA-SECRETASE ACTIVITY; TRANSGENIC MICE; SYNAPTIC PLASTICITY; HIPPOCAMPAL-NEURONS; MEMORY IMPAIRMENTS; MISSENSE MUTATIONS; SPATIAL MEMORY; IN-VIVO; ONSET AB Presenilins play essential roles in memory formation, synaptic function, and neuronal survival. Mutations in the Presenilin-1 (PSEN1) gene are the major cause of familial Alzheimer's disease (FAD). How PSEN1 mutations cause FAD is unclear, and pathogenic mechanisms based on gain or loss of function have been proposed. Here, we generated Psen1 knockin (KI) mice carrying the FAD mutation L435F or C410Y. Remarkably, KI mice homozygous for either mutation recapitulate the phenotypes of Psen1(-/-) mice. Neither mutation altered Psen1 mRNA expression, but both abolished g-secretase activity. Heterozygosity for the KI mutation decreased production of A beta 40 and A beta 42, increased the A beta 42/A beta 40 ratio, and exacerbated A beta deposition. Furthermore, the L435F mutation impairs hippocampal synaptic plasticity and memory and causes age-dependent neurodegeneration in the aging cerebral cortex. Collectively, our findings reveal that FAD mutations can cause complete loss of Presenilin-1 function in vivo, suggesting that clinical PSEN mutations produce FAD through a loss-of-function mechanism. C1 [Xia, Dan; Watanabe, Hirotaka; Wu, Bei; Lee, Sang Hun; Shen, Jie; Kelleher, Raymond J., III] Harvard Univ, Brigham & Womens Hosp, Ctr Neurol Dis, Sch Med,Dept Neurol, Boston, MA 02115 USA. [Xia, Dan; Kelleher, Raymond J., III] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res,Dept Neurol, Boston, MA 02114 USA. [Li, Yan; Tsvetkov, Evgeny; Bolshakov, Vadim Y.] Harvard Univ, Sch Med, McLean Hosp, Dept Psychiat, Belmont, MA 02478 USA. [Bolshakov, Vadim Y.; Shen, Jie; Kelleher, Raymond J., III] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Shen, J (reprint author), Harvard Univ, Brigham & Womens Hosp, Ctr Neurol Dis, Sch Med,Dept Neurol, Boston, MA 02115 USA. EM jshen@rics.bwh.harvard.edu; kelleher@helix.mgh.harvard.edu RI Lee, Sang Hun/C-1198-2015; Tsvetkov, Evgeny/B-6573-2016 OI Lee, Sang Hun/0000-0002-0020-4631; Tsvetkov, Evgeny/0000-0002-6784-0907 FU NIH [R01NS041783, R01NS042818, R01NS075346]; Alzheimer's Association; Pew Scholars Program in the Biomedical Sciences FX We would like to thank T. Sudhof for critical reading of the manuscript, L. Mucke for APP transgenic mice, T. Iwatsubo and T. Tomita for the pTrcHis2A-C100-FmH and pTrcHis2A-N102-FmH plasmids, E. Heilig, T. Ding, and H. Zhao for assistance, and other lab members for helpful discussions. This work was supported by grants from the NIH (R01NS041783 and R01NS042818 to J.S., R01NS075346 to R.J.K.) and the Alzheimer's Association. R.J.K. was supported by the Pew Scholars Program in the Biomedical Sciences. NR 55 TC 48 Z9 48 U1 8 U2 46 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD MAR 4 PY 2015 VL 85 IS 5 BP 967 EP 981 DI 10.1016/j.neuron.2015.02.010 PG 15 WC Neurosciences SC Neurosciences & Neurology GA CD8AZ UT WOS:000351318900011 PM 25741723 ER PT J AU von Bornstadt, D Houben, T Seidel, JL Zheng, Y Dilekoz, E Qin, T Sandow, N Kura, S Eikermann-Haerter, K Endres, M Boas, DA Moskowitz, MA Lo, EH Dreier, JP Woitzik, J Sakadzic, S Ayata, C AF von Bornstaedt, Daniel Houben, Thijs Seidel, Jessica L. Zheng, Yi Dilekoz, Ergin Qin, Tao Sandow, Nora Kura, Sreekanth Eikermann-Haerter, Katharina Endres, Matthias Boas, David A. Moskowitz, Michael A. Lo, Eng H. Dreier, Jens P. Woitzik, Johannes Sakadzic, Sava Ayata, Cenk TI Supply-Demand Mismatch Transients in Susceptible Peri-infarct Hot Zones Explain the Origins of Spreading Injury Depolarizations SO NEURON LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; LASER SPECKLE FLOWMETRY; BLOOD-FLOW; BRAIN-INJURY; FUNCTIONAL ACTIVATION; OXYGEN-METABOLISM; MALIGNANT STROKE; CORTEX; DEPRESSION; HEMORRHAGE AB Peri-infarct depolarizations (PIDs) are seemingly spontaneous spreading depression-like waves that negatively impact tissue outcome in both experimental and human stroke. Factors triggering PIDs are unknown. Here, we show that somatosensory activation of peri-infarct cortex triggers PIDs when the activated cortex is within a critical range of ischemia. We show that the mechanism involves increased oxygen utilization within the activated cortex, worsening the supply-demand mismatch. We support the concept by clinical data showing that mismatch predisposes stroke patients to PIDs as well. Conversely, transient worsening of mismatch by episodic hypoxemia or hypotension also reproducibly triggers PIDs. Therefore, PIDs are triggered upon supply-demand mismatch transients in metastable peri-infarct hot zones due to increased demand or reduced supply. Based on the data, we propose that minimizing sensory stimulation and hypoxic or hypotensive transients in stroke and brain injury would reduce PID incidence and their adverse impact on outcome. C1 [von Bornstaedt, Daniel; Houben, Thijs; Seidel, Jessica L.; Zheng, Yi; Dilekoz, Ergin; Qin, Tao; Eikermann-Haerter, Katharina; Moskowitz, Michael A.; Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Res Lab,Dept Radiol, Charlestown, MA 02129 USA. [von Bornstaedt, Daniel; Endres, Matthias; Dreier, Jens P.] Charite, Dept Neurol, D-10117 Berlin, Germany. [Houben, Thijs] Leiden Univ, Med Ctr, Dept Neurol, NL-2300 RC Leiden, Netherlands. [Dilekoz, Ergin] Gazi Univ, Dept Pharmacol, Fac Med, TR-06560 Ankara, Turkey. [Sandow, Nora; Woitzik, Johannes] Charite, Dept Neurosurg, D-13353 Berlin, Germany. [von Bornstaedt, Daniel; Sandow, Nora; Endres, Matthias; Dreier, Jens P.; Woitzik, Johannes] Charite, Ctr Stroke Res, D-10117 Berlin, Germany. [Kura, Sreekanth; Boas, David A.; Sakadzic, Sava] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Opt Div,MHG MIT HMS Athinoula A Martinos Ctr Biom, Charlestown, MA 02129 USA. [Endres, Matthias] Charite, German Ctr Neurodegenerat Dis DZNE, D-10117 Berlin, Germany. [Endres, Matthias] Charite, German Ctr Cardiovasc Res DZHK, D-10117 Berlin, Germany. [Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA 02129 USA. [Dreier, Jens P.] Charite, Dept Expt Neurol, D-10117 Berlin, Germany. [Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv & Neurosci Intens Care Unit,Dept Neur, Boston, MA 02114 USA. RP Ayata, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Res Lab,Dept Radiol, 149 13th St,6408, Charlestown, MA 02129 USA. EM cayata@partners.org OI Dreier, Jens/0000-0001-7459-2828 FU NIH [NS055104, NS061505]; AHA [11SDG7600037]; Fondation Leducq; Heitman Foundation; Ellison Foundation; Konrad-Adenauer-Foundation; Deutsche Forschungsgemeinschaft [DFG-WO 1704/1-1, DFG DR 323/5-1, SFB TR 43, KFO 247, KFO 213]; EU (European Stroke Network, WakeUp, Counterstroke); Corona Foundation and Bundesministerium fur Bildung und Forschung (Center for Stroke Research Berlin) [01 EO 0801] FX Supported by grants from the NIH (NS055104, NS061505), the AHA (11SDG7600037), the Fondation Leducq, the Heitman Foundation, the Ellison Foundation, the Konrad-Adenauer-Foundation, the Deutsche Forschungsgemeinschaft (DFG-WO 1704/1-1, DFG DR 323/5-1, Excellence cluster Neuro-Cure; SFB TR 43, KFO 247, KFO 213), EU (European Stroke Network, WakeUp, Counterstroke), Corona Foundation and Bundesministerium fur Bildung und Forschung (Center for Stroke Research Berlin, 01 EO 0801). NR 34 TC 20 Z9 20 U1 2 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD MAR 4 PY 2015 VL 85 IS 5 BP 1117 EP 1131 DI 10.1016/j.neuron.2015.02.007 PG 15 WC Neurosciences SC Neurosciences & Neurology GA CD8AZ UT WOS:000351318900021 PM 25741731 ER PT J AU Claycomb, MA Wang, L Sharp, C Ractliffe, KC Elhai, JD AF Claycomb, Meredith A. Wang, Li Sharp, Carla Ractliffe, Kendra C. Elhai, Jon D. TI Assessing Relations between PTSD's Dysphoria and Reexperiencing Factors and Dimensions of Rumination SO PLOS ONE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; CONFIRMATORY FACTOR-ANALYSIS; DEPRESSED MOOD; SYMPTOMS; MEMORIES; DURATION; EPISODES; MODEL AB The purpose of the present study was to investigate the relations between posttraumatic stress disorder's (PTSD) dysphoria and reexperiencing factors and underlying dimensions of rumination. 304 trauma-exposed primary care patients were administered the Stressful Life Events Screening Questionnaire, PTSD Symptom Scale based on their worst traumatic event, and Ruminative Thought Style Questionnaire (RTSQ). Confirmatory factor analyses (CFAs) were conducted to determine the dysphoria and reexperiencing factors' relationships with the four factors of rumination. Results revealed that both the dysphoria and reexperiencing factors related more to problem-focused thinking and anticipatory thoughts than counterfactual thinking. Additionally, the reexperiencing factor related more to anticipatory thinking than repetitive thinking. Clinical and theoretical implications are discussed. C1 [Claycomb, Meredith A.; Elhai, Jon D.] Univ Toledo, Dept Psychol, Toledo, OH 43606 USA. [Wang, Li] Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing 100101, Peoples R China. [Sharp, Carla] Univ Houston, Dept Psychol, Baylor Coll Med, Menninger Clin, Houston, TX USA. [Ractliffe, Kendra C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Elhai, Jon D.] Univ Toledo, Dept Psychiat, Toledo, OH 43606 USA. RP Elhai, JD (reprint author), Univ Toledo, Dept Psychol, Toledo, OH 43606 USA. EM contact@jon-elhai.com OI 王, 力/0000-0002-1459-3412 NR 35 TC 5 Z9 5 U1 1 U2 10 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 MAR 4 PY 2015 VL 10 IS 3 AR e0118435 DI 10.1371/journal.pone.0118435 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CC9JM UT WOS:000350685900034 PM 25738868 ER PT J AU Grove, O Berglund, AE Schabath, MB Aerts, HJWL Dekker, A Wang, H Velazquez, ER Lambin, P Gu, YH Balagurunathan, Y Eikman, E Gatenby, RA Eschrich, S Gillies, RJ AF Grove, Olya Berglund, Anders E. Schabath, Matthew B. Aerts, Hugo J. W. L. Dekker, Andre Wang, Hua Velazquez, Emmanuel Rios Lambin, Philippe Gu, Yuhua Balagurunathan, Yoganand Eikman, Edward Gatenby, Robert A. Eschrich, Steven Gillies, Robert J. TI Quantitative Computed Tomographic Descriptors Associate Tumor Shape Complexity and Intratumor Heterogeneity with Prognosis in Lung Adenocarcinoma SO PLOS ONE LA English DT Article ID TEXTURE ANALYSIS; CT IMAGES; POTENTIAL MARKER; CANCER; SURVIVAL; REPRODUCIBILITY; MUTATIONS AB Two CT features were developed to quantitatively describe lung adenocarcinomas by scoring tumor shape complexity (feature 1: convexity) and intratumor density variation (feature 2: entropy ratio) in routinely obtained diagnostic CT scans. The developed quantitative features were analyzed in two independent cohorts (cohort 1: n = 61; cohort 2: n = 47) of patients diagnosed with primary lung adenocarcinoma, retrospectively curated to include imaging and clinical data. Preoperative chest CTs were segmented semi-automatically. Segmented tumor regions were further subdivided into core and boundary sub-regions, to quantify intensity variations across the tumor. Reproducibility of the features was evaluated in an independent test-retest dataset of 32 patients. The proposed metrics showed high degree of reproducibility in a repeated experiment (concordance, CCC >= 0.897; dynamic range, DR >= 0.92). Association with overall survival was evaluated by Cox proportional hazard regression, Kaplan-Meier survival curves, and the log-rank test. Both features were associated with overall survival (convexity: p = 0.008; entropy ratio: p = 0.04) in Cohort 1 but not in Cohort 2 (convexity: p = 0.7; entropy ratio: p = 0.8). In both cohorts, these features were found to be descriptive and demonstrated the link between imaging characteristics and patient survival in lung adenocarcinoma. C1 [Grove, Olya; Wang, Hua; Gu, Yuhua; Balagurunathan, Yoganand; Gatenby, Robert A.; Gillies, Robert J.] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Imaging & Metab, Tampa, FL 33612 USA. [Berglund, Anders E.; Eschrich, Steven] H Lee Moffitt Canc Ctr & Res Inst, Dept Biomed Informat, Tampa, FL USA. [Schabath, Matthew B.] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA. [Eikman, Edward; Gatenby, Robert A.; Gillies, Robert J.] H Lee Moffitt Canc Ctr & Res Inst, Dept Radiol, Tampa, FL USA. [Dekker, Andre; Lambin, Philippe] Maastricht Univ, Res Inst GROW, MAASTRO Clin, Dept Radiat Oncol, NL-6229 ET Maastricht, Netherlands. [Wang, Hua] Tianjin Med Univ, Key Lab Canc Prevent & Therapy, Canc Inst & Hosp, Dept Radiol,Natl Clin Res Ctr Canc, Tianjin, Peoples R China. [Aerts, Hugo J. W. L.; Velazquez, Emmanuel Rios] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA USA. [Aerts, Hugo J. W. L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA USA. RP Gillies, RJ (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Imaging & Metab, Tampa, FL 33612 USA. EM Robert.Gillies@Moffitt.org RI Aerts, Hugo/P-6350-2015; Schabath, Matthew/J-3763-2016; OI Aerts, Hugo/0000-0002-2122-2003; Schabath, Matthew/0000-0003-3241-3216; Dekker, Andre/0000-0002-0422-7996 FU National Cancer Institute; NIH/NCI, Radiomics of NSCLC [U01CA143062]; NIH/NCI, Radiomics of Lung Cancer Screening [P50CA119997]; Florida Biomedical Research Programs: King Team Science Grant [2KT01] FX Funding provided by National Cancer Institute: http://www.cancer.gov/, 1.NIH/NCI U01CA143062, Radiomics of NSCLC; 2. NIH/NCI P50CA119997, Radiomics of Lung Cancer Screening. Florida Biomedical Research Programs: http://researchtest.magnet.fsu.edu/newsletters/2013/July/documents/2013- 2014%20SUMMER%20CALL%20King%20Program.pdf, King Team Science Grant 2KT01. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 28 TC 20 Z9 20 U1 1 U2 10 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 MAR 4 PY 2015 VL 10 IS 3 AR e0118261 DI 10.1371/journal.pone.0118261 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CC9JM UT WOS:000350685900026 PM 25739030 ER PT J AU Reategui, E Aceto, N Lim, EJ Sullivan, JP Jensen, AE Zeinali, M Martel, JM Aranyosi, AJ Li, W Castleberry, S Bardia, A Sequist, LV Haber, DA Maheswaran, S Hammond, PT Toner, M Stott, SL AF Reategui, Eduardo Aceto, Nicola Lim, Eugene J. Sullivan, James P. Jensen, Anne E. Zeinali, Mahnaz Martel, Joseph M. Aranyosi, Alexander J. Li, Wei Castleberry, Steven Bardia, Aditya Sequist, Lecia V. Haber, Daniel A. Maheswaran, Shyamala Hammond, Paula T. Toner, Mehmet Stott, Shannon L. TI Tunable Nanostructured Coating for the Capture and Selective Release of Viable Circulating Tumor Cells SO ADVANCED MATERIALS LA English DT Article ID BREAST-CANCER; EFFICIENT CAPTURE; MELANOMA-CELLS; WHOLE-BLOOD; NANOMATERIALS; METASTASIS; MUTATIONS; EGFR AB A layer-by-layer gelatin nanocoating is presented for use as a tunable, dual response biomaterial for the capture and release of circulating tumor cells (CTCs) from cancer patient blood. The entire nanocoating can be dissolved from the surface of microfluidic devices through biologically compatible temperature shifts. Alternatively, individual CTCs can be released through locally applied mechanical stress. C1 [Reategui, Eduardo; Lim, Eugene J.; Jensen, Anne E.; Zeinali, Mahnaz; Martel, Joseph M.; Aranyosi, Alexander J.; Toner, Mehmet; Stott, Shannon L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Charlestown, MA 02129 USA. [Reategui, Eduardo; Martel, Joseph M.; Toner, Mehmet; Stott, Shannon L.] Harvard Univ, Sch Med, Shriners Hosp Children, Boston, MA 02114 USA. [Reategui, Eduardo; Martel, Joseph M.; Toner, Mehmet] Harvard Univ, Med Sch 55, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Aceto, Nicola; Sullivan, James P.; Bardia, Aditya; Sequist, Lecia V.; Haber, Daniel A.; Maheswaran, Shyamala] Harvard Univ, Med Sch Boston, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Lim, Eugene J.] MIT, Dept Elect Engn, Cambridge, MA 02139 USA. [Li, Wei; Castleberry, Steven; Hammond, Paula T.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Stott, Shannon L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Stott, SL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Bldg 114,16th St, Charlestown, MA 02129 USA. EM sstott@mgh.harvard.edu RI Li, Wei/P-3546-2016; OI Li, Wei/0000-0002-4738-1475; Aranyosi, Alexander/0000-0002-8133-5026 FU Stand Up to Cancer; Howard Hughes Medical Institute; NIH [CA129933, P41 EB002503-11]; National Institute for Biomedical Imaging and Bioengineering (NIBIB) [EB008047] FX The authors acknowledge all our patients who participated in this study and the healthy volunteers who kindly donated their blood. Blood specimens for CTC isolation were obtained after informed patient consent according to institutional review board (IRB) protocol (05-300), at the Massachusetts General Hospital. This work was supported by grants from Stand Up to Cancer (D.A.H., M.T., S.M.), Howard Hughes Medical Institute (D.A.H.), NIH CA129933 (D.A.H.), National Institute for Biomedical Imaging and Bioengineering (NIBIB) EB008047 (M.T., D.A.H.), NIH P41 EB002503-11 (M.T.). Thanks to Laura Libby and Octavio Hurtado for expert technical support. Thanks to Bavand Keshavarz for helping with microtip design, Matthew Phillips for the CTC enumeration scans, Thomas Carey for the atomic force microscopy analysis, and Charles P. Lai for the nanoparticle size characterization. NR 33 TC 33 Z9 33 U1 40 U2 180 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 0935-9648 EI 1521-4095 J9 ADV MATER JI Adv. Mater. PD MAR 4 PY 2015 VL 27 IS 9 BP 1593 EP + DI 10.1002/adma.201404677 PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA CC7IO UT WOS:000350541100015 PM 25640006 ER PT J AU Blount, JW Redan, BW Ferruzzi, MG Reuhs, BL Cooper, BR Harwood, JS Shulaev, V Pasinetti, G Dixon, RA AF Blount, Jack W. Redan, Benjamin W. Ferruzzi, Mario G. Reuhs, Bradley L. Cooper, Bruce R. Harwood, John S. Shulaev, Vladimir Pasinetti, Giulio Dixon, Richard A. TI Synthesis and Quantitative Analysis of Plasma-Targeted Metabolites of Catechin and Epicatechin SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE catechin; glucuronosylation; O-methylation; phase II metabolites; semisynthesis; structure determination; two-site validation ID (-)-EPICATECHIN METABOLITES; GASTROINTESTINAL-TRACT; ALZHEIMERS-DISEASE; ORAL INGESTION; RAT PLASMA; IN-VIVO; MATRIX; BIOAVAILABILITY; PROCYANIDINS; FLAVAN-3-OLS AB Grape seed polyphenolic extract (GSPE) rich in the flavan-3-ols (+)-catechin and (-)-epicatechin beneficially modulates Alzheimer's Disease phenotypes in animal models. The parent molecules in the extract are converted to a series of methylated and glucuronidated derivatives. To fully characterize these metabolites and establish a robust quantitative assay of their levels in biological fluids, we have implemented a partial synthetic approach utilizing chemical methylation followed by enzymatic glucuronidation. Liquid chromatography/time-of-flight mass spectrometry (LC-TOF-MS) and nuclear magnetic resonance (NMR) spectroscopy were used to assign unequivocal structures to the compounds. An analytical method using solid-phase extraction and LC-MS/MS in selective reaction monitoring mode (SRM) was validated for their quantitation in plasma. These studies provide a basis for improvements in future work on the bioavailability, metabolism, and mechanism of action of metabolites derived from dietary flavan-3-ols in a range of interventions. C1 [Blount, Jack W.; Shulaev, Vladimir; Dixon, Richard A.] Univ N Texas, Dept Biol Sci, Denton, TX 76203 USA. [Redan, Benjamin W.; Ferruzzi, Mario G.; Reuhs, Bradley L.] Purdue Univ, Dept Nutr Sci, W Lafayette, IN 47907 USA. [Ferruzzi, Mario G.] Purdue Univ, Dept Food Sci, W Lafayette, IN 47907 USA. [Pasinetti, Giulio] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Pasinetti, Giulio] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Cooper, Bruce R.] Purdue Univ, Bindley Biosci Ctr Metabolite Profiling Facil, W Lafayette, IN 47907 USA. [Harwood, John S.] Purdue Univ, Purdue Interdept NMR Facil, W Lafayette, IN 47907 USA. [Harwood, John S.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. RP Dixon, RA (reprint author), Univ N Texas, Dept Biol Sci, 1155 Union Circle 305220, Denton, TX 76203 USA. EM Richard.Dixon@unt.edu FU National Institutes of Health [5 PO1 AT004511-05]; University of North Texas; Purdue University; Career Scientist Award in the Research and Development unit; National Science Foundation [DGE-1333468] FX This work was supported by National Institutes of Health grant 5 PO1 AT004511-05 Administrative Supplement to G.P. and by the University of North Texas and Purdue University. This material is also the result of work supported in part with resources and the use of facilities at the James J. Peters Veterans Affairs Medical Center, Bronx, NY. In addition, GMP holds a Career Scientist Award in the Research and Development unit and is the Director of the Basic and Biomedical Research and Training Program, GRECC, James J. Peters Veterans Affairs Medical Center. We acknowledge that the contents of this manuscript do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. B.W.R. is supported by National Science Foundation grant DGE-1333468. NR 27 TC 4 Z9 4 U1 7 U2 50 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 EI 1520-5118 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAR 4 PY 2015 VL 63 IS 8 BP 2233 EP 2240 PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA CC8JR UT WOS:000350615000014 PM 25671729 ER PT J AU Akamatsu, Y Nishijima, Y Lee, CC Yang, SY Shi, L An, L Wang, RK Tominaga, TJ Liu, JL AF Akamatsu, Yosuke Nishijima, Yasuo Lee, Chih Cheng Yang, Shih Yen Shi, Lei An, Lin Wang, Ruikang K. Tominaga, Teiji Liu, Jialing TI Impaired Leptomeningeal Collateral Flow Contributes to the Poor Outcome following Experimental Stroke in the Type 2 Diabetic Mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE anastomosis; arteriogenesis; Doppler OCT; MCAO; metabolic syndrome; vascular remodeling ID ACUTE ISCHEMIC-STROKE; FOCAL CEREBRAL-ISCHEMIA; PLASMINOGEN-ACTIVATOR INHIBITOR-1; MARKED NEUROPROTECTIVE EFFICACY; ALBUMIN THERAPY; BLOOD-FLOW; IN-VIVO; MICROVASCULAR RESPONSES; SERUM-ALBUMIN; HYPERGLYCEMIA AB Collateral status is an independent predictor of stroke outcome. However, the spatiotemporal manner in which collateral flow maintains cerebral perfusion during cerebral ischemia is poorly understood. Diabetes exacerbates ischemic brain damage, although the impact of diabetes on collateral dynamics remains to be established. Using Doppler optical coherent tomography, a robust recruitment of leptomeningeal collateral flow was detected immediately after middle cerebral artery ( MCA) occlusion in C57BL/6 mice, and it continued to grow over the course of 1 week. In contrast, an impairment of collateral recruitment was evident in the Type 2 diabetic db/db mice, which coincided with a worse stroke outcome compared with their normoglycemic counterpart db/+, despite their equally well-collateralized leptomeningeal anastomoses. Similar to the wild-type mice, both db/+ and db/db mice underwent collateral growth 7 d after MCA stroke, although db/db mice still exhibited significantly reduced retrograde flow into the MCA territory chronically. Acutely induced hyperglycemia in the db/+ mice did not impair collateral flow after stroke, suggesting that the state of hyperglycemia alone was not sufficient to impact collateral flow. Human albumin was efficacious in improving collateral flow and outcome after stroke in the db/db mice, enabling perfusion to proximal MCA territory that was usually not reached by retrograde flow from anterior cerebral artery without treatment. Our results suggest that the impaired collateral status contributes to the exacerbated ischemic injury in mice with Type 2 diabetes, and modulation of collateral flow has beneficial effects on stroke outcome among these subjects. C1 [Akamatsu, Yosuke; Nishijima, Yasuo; Lee, Chih Cheng; Yang, Shih Yen; Liu, Jialing] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94121 USA. [Akamatsu, Yosuke; Nishijima, Yasuo; Lee, Chih Cheng; Yang, Shih Yen; Liu, Jialing] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Akamatsu, Yosuke; Nishijima, Yasuo; Tominaga, Teiji] Tohoku Univ, Grad Sch Med, Dept Neurosurg, Sendai, Miyagi 9808574, Japan. [Shi, Lei; An, Lin; Wang, Ruikang K.] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. [Shi, Lei; An, Lin; Wang, Ruikang K.] Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA. RP Liu, JL (reprint author), Univ Calif San Francisco, Dept Neurol Surg 112C, 1700 Owens St, San Francisco, CA 94158 USA. EM jialing.liu@ucsf.edu RI Liu, Jialing/A-8627-2012 OI Liu, Jialing/0000-0003-4420-4382 FU National Institutes of Health [R01 NS071050]; Veterans Administration Merit Award [I01RX000655]; American Heart Hospital Association [EIA 0940065N]; NIH [R01HL093140] FX This work was supported by National Institutes of Health Grant R01 NS071050 to J.L., Veterans Administration Merit Award I01RX000655 to J. L., American Heart Hospital Association EIA 0940065N to J.L., and NIH R01HL093140 to R.K.W. We thank Dr. Philip Weinstein (University of California at San Francisco) for helpful discussion and Ilona Garner (University of California at San Francisco) for editorial assistance. NR 55 TC 13 Z9 13 U1 1 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 4 PY 2015 VL 35 IS 9 BP 3851 EP 3864 DI 10.1523/JNEUROSCI.3838-14.2015 PG 14 WC Neurosciences SC Neurosciences & Neurology GA CD0DP UT WOS:000350740900013 PM 25740515 ER PT J AU Thomson, D Turner, A Lauder, S Gigler, ME Berk, L Singh, AB Pasco, JA Berk, M Sylvia, L AF Thomson, Daniel Turner, Alyna Lauder, Sue Gigler, Margaret E. Berk, Lesley Singh, Ajeet B. Pasco, Julie A. Berk, Michael Sylvia, Louisa TI A brief review of exercise, bipolar disorder, and mechanistic pathways SO FRONTIERS IN PSYCHOLOGY LA English DT Review DE bipolar disorder; exercise; mechanistic pathways; depression; hypomania; neurogenesis ID APPROACH SYSTEM BAS; PHYSICAL-ACTIVITY; PSYCHIATRIC-DISORDERS; SPECTRUM DISORDERS; RANDOMIZED-TRIALS; MENTAL-ILLNESS; BLOOD-PRESSURE; DEPRESSION; SYMPTOMS; STRESS AB Despite evidence that exercise has been found to be effective in the treatment of depression, it is unclear whether these data can be extrapolated to bipolar disorder. Available evidence for bipolar disorder is scant, with no existing randomized controlled trials having tested the impact of exercise on depressive, manic or hypomanic symptomatology. Although exercise is often recommended in bipolar disorder, this is based on extrapolation from the unipolar literature, theory and clinical expertise and not empirical evidence. In addition, there are currently no available empirical data on program variables, with practical implications on frequency, intensity and type of exercise derived from unipolar depression studies. The aim of the current paper is to explore the relationship between exercise and bipolar disorder and potential mechanistic pathways. Given the high rate of medical co-morbidities experienced by people with bipolar disorder, it is possible that exercise is a potentially useful and important intervention with regard to general health benefits; however, further research is required to elucidate the impact of exercise on mood symptomology. C1 [Thomson, Daniel] RMIT Univ, Dept Appl Sci, Bundoora, Vic, Australia. [Turner, Alyna; Berk, Lesley; Singh, Ajeet B.; Pasco, Julie A.; Berk, Michael] Deakin Univ, Innovat Mental & Phys Hlth & Clin Treatment Strat, Sch Med, Geelong, Vic 3220, Australia. [Turner, Alyna; Lauder, Sue; Berk, Michael] Univ Melbourne, Dept Psychiat, Parkville, Vic 3052, Australia. [Turner, Alyna] Univ Newcastle, Sch Med & Publ Hlth, Ctr Translat Neurosci & Mental Hlth, Callaghan, NSW 2308, Australia. [Lauder, Sue] Federat Univ Australia, Ballarat, NC, Australia. [Gigler, Margaret E.; Sylvia, Louisa] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Berk, Lesley] Deakin Univ, Sch Psychol, Mental Hlth & Wellbeing Strateg Res Ctr, Greelong, Vic, Australia. [Pasco, Julie A.] Univ Melbourne, North West Acad Ctr, Dept Med, St Albans, Vic, Australia. [Berk, Michael] Furey Inst Neurosci & Mental Hlth, Parkville, Vic, Australia. [Berk, Michael] Natl Ctr Excellence Youth Mental Hlth, Orygen, Parkville, Vic, Australia. [Sylvia, Louisa] Harvard Univ, Harvard Med Sch, Boston, MA 02115 USA. RP Turner, A (reprint author), Deakin Univ, Innovat Mental & Phys Hlth & Clin Treatment Strat, Sch Med, Kitchener House,POB 281, Geelong, Vic 3220, Australia. EM alyna.turner@barwonhealth.org.au OI Berk, Lesley/0000-0002-3677-7503 FU NHMRC; Perpetual; Amgen (Europe) GmBH; BUPA Foundation; Amgen; Sanofi Aventis; NHMRC Senior Principal Research Fellowship [1059660]; NTH; Cooperative Research Centre; Simons Autism Foundation; Cancer Council of Victoria; Stanley Medical Research Foundation; MBF; Beyond Blue; Rotary Health; Geelong Medical Research Foundation; Bristol Myers Squibb; Eli Lilly; Glaxo SmithKline; Meat and Livestock Board; Organon; Novartis; Mayne Pharma; Servier; Woolworths FX No funding has been received to support this study, Ajeet B. Singh is a casual speaker for Servier Australia, Pfizer Australia, and Lundbeck Australia. Julie A. Pasco has received grant/research support from the NHMRC, Perpetual, Amgen (Europe) GmBH, and BUPA Foundation and has received speaker fees from Amgen and Sanofi Aventis. Michael Berk is supported by a NHMRC Senior Principal Research Fellowship 1059660 and has received Grant/Research Support from the NTH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Rotary Health, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Meat and Livestock Board, Organon, Novartis, Mayne Pharma, Servier and Woolworths, has been a speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay and Wyeth, and served as a consultant to Astra Zeneca, Bioadvaraex, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck Merck and Servier. Louisa Sylvia was a shareholder in Concordant Rater Systems and serves as a consultant for United Biosource Corporation, Clinical Trials Network and Institute, Clintara. She receives royalties from New Harbinger. NR 77 TC 9 Z9 9 U1 6 U2 27 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-1078 J9 FRONT PSYCHOL JI Front. Psychol. PD MAR 4 PY 2015 VL 6 AR 147 DI 10.3389/fpsyg.2015.00147 PG 10 WC Psychology, Multidisciplinary SC Psychology GA CC3WP UT WOS:000350282000001 PM 25788889 ER PT J AU Hatfield, SM Kjaergaard, J Lukashev, D Schreiber, TH Belikoff, B Abbott, R Sethumadhavan, S Philbrook, P Ko, K Cannici, R Thayer, M Rodig, S Kutok, JL Jackson, EK Karger, B Podack, ER Ohta, A Sitkovsky, MV AF Hatfield, Stephen M. Kjaergaard, Jorgen Lukashev, Dmitriy Schreiber, Taylor H. Belikoff, Bryan Abbott, Robert Sethumadhavan, Shalini Philbrook, Phaethon Ko, Kami Cannici, Ryan Thayer, Molly Rodig, Scott Kutok, Jeffrey L. Jackson, Edwin K. Karger, Barry Podack, Eckhard R. Ohta, Akio Sitkovsky, Michail V. TI Immunological mechanisms of the antitumor effects of supplemental oxygenation SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID NEGATIVE BREAST-CANCER; T REGULATORY CELLS; LUNG INJURY; ADOPTIVE IMMUNOTHERAPY; THERAPEUTIC-EFFICACY; TUMOR INFILTRATION; ADENOSINE RELEASE; DOWN-REGULATION; HYPOXIA; RECEPTOR AB Antitumor T cells either avoid or are inhibited in hypoxic and extracellular adenosine-rich tumor microenvironments (TMEs) by A2A adenosine receptors. This may limit further advances in cancer immunotherapy. There is a need for readily available and safe treatments that weaken the hypoxia-A2-adenosinergic immunosuppression in the TME. Recently, we reported that respiratory hyperoxia decreases intratumoral hypoxia and concentrations of extracellular adenosine. We show that it also reverses the hypoxia-adenosinergic immunosuppression in the TME. This, in turn, stimulates (i) enhanced intratumoral infiltration and reduced inhibition of endogenously developed or adoptively transfered tumor-reactive CD8 T cells, (ii) increased proinflammatory cytokines and decreased immunosuppressive molecules, such as transforming growth factor-beta (TGF-beta), (iii) weakened immunosuppression by regulatory T cells, and (iv) improved lung tumor regression and long-term survival in mice. Respiratory hyperoxia also promoted the regression of spontaneous metastasis from orthotopically grown breast tumors. These effects are entirely T cell- and natural killer cell- dependent, thereby justifying the testing of supplemental oxygen as an immunological coadjuvant to combine with existing immunotherapies for cancer. C1 [Hatfield, Stephen M.; Kjaergaard, Jorgen; Lukashev, Dmitriy; Belikoff, Bryan; Abbott, Robert; Sethumadhavan, Shalini; Philbrook, Phaethon; Ko, Kami; Cannici, Ryan; Thayer, Molly; Ohta, Akio; Sitkovsky, Michail V.] Northeastern Univ, New England Inflammat & Tissue Protect Inst, Boston, MA 02115 USA. [Schreiber, Taylor H.; Podack, Eckhard R.] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA. [Rodig, Scott; Kutok, Jeffrey L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Jackson, Edwin K.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15219 USA. [Karger, Barry] Northeastern Univ, Barnett Inst Chem & Biol Anal, Boston, MA 02115 USA. [Sitkovsky, Michail V.] Harvard Inst Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. RP Sitkovsky, MV (reprint author), Northeastern Univ, New England Inflammat & Tissue Protect Inst, 360 Huntington Ave, Boston, MA 02115 USA. EM m.sitkovsky@neu.edu FU Northeastern University; NIH [R01 CA 112561, R01 CA 111985, R21 AT 002788, U19 AI 091693]; National Cancer Institute [5PO1CA109094-03]; National Institute of Allergy and Infectious Diseases 1P01 grant [AI096396-01 3, HL109002, DK091190, DK068575, DK079307, CA168628]; Bankhead-Coley Postdoctoral Fellowship; NIH (Dana-Farber Cancer Institute); NIH (Harvard Medical School-Northeastern University Joint Program in Cancer Drug Development) FX This work was supported by funding from Northeastern University and NIH grants to M.V.S. (R01 CA 112561, R01 CA 111985, R21 AT 002788, U19 AI 091693, Dana-Farber Cancer Institute, and Harvard Medical School-Northeastern University Joint Program in Cancer Drug Development) as well as by National Cancer Institute grant 5PO1CA109094-03 and National Institute of Allergy and Infectious Diseases 1P01 grant AI096396-01 3 to E.R.P.; HL109002, DK091190, DK068575, DK079307, and CA168628 to E.K.J.; and a Bankhead-Coley Postdoctoral Fellowship to T.H.S. NR 49 TC 35 Z9 36 U1 2 U2 20 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 MAR 4 PY 2015 VL 7 IS 277 AR 277ra30 DI 10.1126/scitranslmed.aaa1260 PG 12 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CC4YE UT WOS:000350361800006 PM 25739764 ER PT J AU Kim, HI Kim, JA Choi, EJ Harris, JB Jeong, SY Son, SJ Kim, Y Shin, OS AF Kim, Hyung-Ip Kim, Ji-Ae Choi, Eun-Jin Harris, Jason B. Jeong, Seong-Yeop Son, Seok-Jun Kim, Younghoon Shin, Ok Sarah TI In vitro and in vivo antimicrobial efficacy of natural plant-derived compounds against Vibrio cholerae of O1 El Tor Inaba serotype SO BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY LA English DT Article DE magnolol; honokiol; V. cholerae; C. elegans; antibacterial effect ID KAPPA-B ACTIVATION; CAENORHABDITIS-ELEGANS; STAPHYLOCOCCUS-AUREUS; BACTERICIDAL ACTIVITY; BIOFILMS ENHANCE; HONOKIOL; MAGNOLOL; CELLS; INHIBITION; EMERGENCE AB In this study, we investigated antibacterial activities of 20 plant-derived natural compounds against Gram-negative enteric pathogens. We found that both flavonoids and non-flavonoids, including honokiol and magnolol, possess specific antibacterial activities against V. cholerae, but not against other species of Gram-negative bacterium which we tested. Using various antibacterial assays, we determined that there was a dose-dependent bactericidal and biofilm inhibitory activity of honokiol and magnolol against Vibrio cholerae. In addition to antibacterial activities, these molecules also induced an attenuating effect on reactive oxygen species (ROS) production and pro-inflammatory responses generated by macrophages in response to lipopolysaccharides (LPS). Additionally, Caenorhabditis elegans lethality assay revealed that honokiol and magnolol have an ability to extend a lifespan of V. cholerae-infected worms, contributing to prolonged survival of worms after lethal infection. Altogether, our data show for the first time that honokiol and magnolol may be considered as attractive protective or preventive food adjuncts for cholera. C1 [Kim, Hyung-Ip; Kim, Ji-Ae; Shin, Ok Sarah] Korea Univ, Coll Med, Dept Biomed Sci, Seoul 136705, South Korea. [Choi, Eun-Jin] Korea Univ, Coll Med, Asian Pacific Influenza Inst, Seoul 136705, South Korea. [Harris, Jason B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Jeong, Seong-Yeop] MIFI, Sunchang Gun, South Korea. [Son, Seok-Jun; Kim, Younghoon] Chonbuk Natl Univ, Dept Anim Sci, Plus Grad Program BK21, Jeonju 561756, South Korea. [Son, Seok-Jun; Kim, Younghoon] Chonbuk Natl Univ, Inst Agr Sci & Technol, Jeonju 561756, South Korea. [Shin, Ok Sarah] Korea Univ, Coll Med, Dept Microbiol, Seoul 136705, South Korea. RP Kim, Y (reprint author), Chonbuk Natl Univ, Dept Anim Sci, Plus Grad Program BK21, Jeonju 561756, South Korea. EM ykeys2584@jbnu.ac.kr FU Ministry for Health & Welfare, Republic of Korea [R1306922]; Rural Development Administration, Republic of Korea [PJ009990032014] FX Korean Health Technology R&D Projects (R1306922), Ministry for Health & Welfare, Republic of Korea (O.S.S), and by the Cooperative Research Program for Agriculture Science & Technology Development (PJ009990032014), Rural Development Administration, Republic of Korea (S.Y.J.). NR 38 TC 4 Z9 5 U1 1 U2 15 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0916-8451 EI 1347-6947 J9 BIOSCI BIOTECH BIOCH JI Biosci. Biotechnol. Biochem. PD MAR 4 PY 2015 VL 79 IS 3 BP 475 EP 483 DI 10.1080/09168451.2014.991685 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry, Applied; Food Science & Technology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry; Food Science & Technology GA CC6JE UT WOS:000350470400017 PM 25516242 ER PT J AU Sinclair, SJ Smith, M Chung, WJ Liebman, R Stein, MB Antonius, D Siefert, CJ Haggerty, G Blais, MA AF Sinclair, Samuel Justin Smith, Michaela Chung, Wei-Jean Liebman, Rachel Stein, Michelle B. Antonius, Daniel Siefert, Caleb J. Haggerty, Greg Blais, Mark A. TI Extending the Validity of the Personality Assessment Inventory's (PAI) Level of Care Index (LOCI) in Multiple Psychiatric Settings SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID SERVICE UTILIZATION; HOSPITALIZATION; SCHIZOPHRENIA; SAMPLE AB The purpose of this study was to extend the validity and clinical application of the Level of Care Index (LOCI) from the Personality Assessment Inventory (PAI) in 2 independent psychiatric samples. In Study 1 (N = 201), the LOCI effectively differentiated level of care (inpatients from outpatients), and was also meaningfully associated with risk factors for psychiatric admission (e.g., suicidal ideation, self-harming behavior, previous psychiatric admission, etc.), even after controlling for other demographic variables (range of Cohen's ds = 0.57-1.00). Likewise, the LOCI also incremented other risk indicators (suicide and violence history) and relevant PAI indexes (i.e., Mean Clinical Elevation, and Suicide and Violence Potential) in predicting level of care, and explained an additional 6% to 12% of variance in the target variable. Diagnostic efficiency analyses indicated LOCI scores in the range of 15 to 18 optimize positive and negative predictive power, and classification rate. In Study 2 (N = 96), the LOCI was found to be significantly higher in those with a recent psychiatric admission within the past 6 months (d = 0.64), as compared to those without an admission. Similarly, those who were admitted for suicide risk had significantly higher mean LOCI scores as compared to those who did not (d = 0.70). The clinical implications of these findings and potential application of the LOCI are discussed. C1 [Sinclair, Samuel Justin; Smith, Michaela; Chung, Wei-Jean; Liebman, Rachel; Stein, Michelle B.; Blais, Mark A.] Massachusetts Gen Hosp, Psychol Evaluat & Res Lab PEaRL, Boston, MA 02114 USA. [Sinclair, Samuel Justin; Smith, Michaela; Chung, Wei-Jean; Liebman, Rachel; Stein, Michelle B.; Blais, Mark A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Antonius, Daniel] SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. [Antonius, Daniel] NYU, Dept Psychiat, Sch Med, New York, NY 10003 USA. [Siefert, Caleb J.] Univ Michigan Dearborn, Dept Behav Sci, Dearborn, MI USA. [Haggerty, Greg] Nassau Univ, Von Tauber Inst Global Psychiat, Med Ctr, E Meadow, NY USA. RP Sinclair, SJ (reprint author), Massachusetts Gen Hosp, Psychol Evaluat & Res Lab PEaRL, One Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM SJSinclair@MGH.Harvard.Edu NR 26 TC 0 Z9 0 U1 0 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0022-3891 EI 1532-7752 J9 J PERS ASSESS JI J. Pers. Assess. PD MAR 4 PY 2015 VL 97 IS 2 BP 145 EP 152 DI 10.1080/00223891.2014.941441 PG 8 WC Psychology, Clinical; Psychology, Social SC Psychology GA CB2JZ UT WOS:000349454700005 PM 25101817 ER PT J AU Ruben, MA Hall, JA Mast, MS AF Ruben, Mollie A. Hall, Judith A. Mast, Marianne Schmid TI Smiling in a Job Interview: When Less Is More SO JOURNAL OF SOCIAL PSYCHOLOGY LA English DT Article DE smiling; interview context; nonverbal behavior; hiring decisions; impression management ID NONVERBAL BEHAVIOR; EMPLOYMENT INTERVIEWS; SELECTION INTERVIEW; METAANALYSIS; FEMALE; COMMUNICATION; JUDGMENTS; PERFORMANCE; APPLICANTS; TACTICS AB Two studies examined the effect of applicants' smiling on hireability. In a pre-test study, participants were asked to rate the expected behavior for four types of applicants. Newspaper reporter applicants were expected to be more serious than applicants for other jobs. In Study 1, participants were randomly assigned to be an applicant or interviewer for a newspaper reporting job. Smiling was negatively related to hiring, and smiling mediated the relation between applicants' motivation to make a good impression and hiring. Hiring was maximized when applicants smiled less in the middle of the interview relative to the start and end. In Study 2, participants watched Study 1 clips and were randomly assigned to believe the applicants were applying to one of four jobs. Participants rated more suitability when applicants smiled less, especially for jobs associated with a serious demeanor. This research shows that job type is an important moderator of the impact of smiling on hiring. C1 [Ruben, Mollie A.] US Dept Vet Affairs, Ctr Healthcare Org & Implementat Res, Boston, MA 02130 USA. [Hall, Judith A.] Northeastern Univ, Dept Psychol, Boston, MA USA. [Mast, Marianne Schmid] Univ Lausanne, Dept Org Behav, CH-1015 Lausanne, Switzerland. RP Ruben, MA (reprint author), US Dept Vet Affairs, Ctr Healthcare Org & Implementat Res, 150 S Huntington Ave,Bldg 9, Boston, MA 02130 USA. EM mollie.ruben@va.gov OI Ruben, Mollie/0000-0001-8918-8932 NR 33 TC 2 Z9 2 U1 2 U2 28 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0022-4545 EI 1940-1183 J9 J SOC PSYCHOL JI J. Soc. Psychol. PD MAR 4 PY 2015 VL 155 IS 2 BP 107 EP 126 DI 10.1080/00224545.2014.972312 PG 20 WC Psychology, Social SC Psychology GA CB0PG UT WOS:000349328100003 PM 25309976 ER PT J AU Olds, PK Kiwanuka, JP Nansera, D Huang, Y Bacchetti, P Jin, CS Gandhi, M Haberer, JE AF Olds, Peter K. Kiwanuka, Julius P. Nansera, Denis Huang, Yong Bacchetti, Peter Jin, Chengshi Gandhi, Monica Haberer, Jessica E. TI Assessment of HIV antiretroviral therapy adherence by measuring drug concentrations in hair among children in rural Uganda SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE human immunodeficiency virus; Uganda; adherence; children; antiretroviral therapy ID SELF-REPORT MEASURES; TANDEM MASS-SPECTROMETRY; INFECTED CHILDREN; HIV-1-INFECTED PATIENTS; VIROLOGICAL RESPONSE; VIRAL LOAD; RESISTANCE; INDINAVIR; ASSOCIATION; EFAVIRENZ AB Current tools for measuring medication adherence have significant limitations, especially among pediatric populations. We conducted a prospective observational study to assess the use of antiretroviral (ARV) drug levels in hair for evaluating antiretroviral therapy (ART) adherence among HIV-infected children in rural Uganda. Three-day caregiver recall, 30-day visual analog scale (VAS), Medication Event Monitoring System (MEMS), and unannounced pill counts and liquid formulation weights (UPC) were collected monthly over a one-year period. Hair samples were collected quarterly and analyzed for nevirapine (NVP) levels, and plasma HIV RNA levels were collected every six months. Among children with at least one hair sample collected, we used univariable random intercept linear regression models to compare log transformed NVP concentrations with each adherence measure, and the child's age, sex, and CD4 count percentage (CD4%). One hundred and twenty-one children aged 2-10 years were enrolled in the study; 74 (61%) provided at least one hair sample, and the mean number of hair samples collected per child was 1.9 (standard deviation [SD] 1.0). Three-day caregiver recall, VAS, and MEMS were found to be positively associated with increasing NVP concentration in hair, although associations were not statistically significant. UPC was found to have a nonsignificant negative association with increasing hair NVP concentration. In conclusion, NVP drug concentrations in hair were found to have nonsignificant, although generally positive, associations with other adherence measures in a cohort of HIV-infected children in Uganda. Hair collection in this population proved challenging, suggesting the need for community education and buy-in with the introduction of novel methodologies. C1 [Olds, Peter K.; Haberer, Jessica E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02163 USA. [Kiwanuka, Julius P.; Nansera, Denis] Mbarara Univ Sci & Technol, Dept Paediat, Mbarara, Uganda. [Huang, Yong; Bacchetti, Peter; Jin, Chengshi; Gandhi, Monica] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Haberer, Jessica E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Haberer, Jessica E.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. RP Haberer, JE (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02163 USA. EM JHABERER@partners.org FU NIAID NIH HHS [R01 AI065233, 3R01AI065233-05S2, R01AI098472, U01 AI034989, R01 AI098472]; NIMH NIH HHS [R21 MH083306, K23MH087228, R21MH083306, K23 MH087228] NR 47 TC 4 Z9 4 U1 4 U2 15 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD MAR 4 PY 2015 VL 27 IS 3 BP 327 EP 332 DI 10.1080/09540121.2014.983452 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA CA1HI UT WOS:000348663000009 PM 25483955 ER PT J AU Barocas, JA Erlandson, KM Belzer, BK Hess, T Sosman, J AF Barocas, Joshua A. Erlandson, Kristine M. Belzer, Blythe K. Hess, Timothy Sosman, James TI Advance directives among people living with HIV: room for improvement SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE patient care; outpatient clinic; HIV/AIDS; advance care planning; advance directives ID OF-LIFE CARE; CANCER-PATIENTS; HEART-FAILURE; ATTITUDES; COMPLETION; BARRIERS; DISEASE; COMMUNICATION; ADULTS; INTERVENTION AB While HIV has become a largely chronic disease, age-associated comorbidities are prevalent in people living with HIV (PLWH). Therefore, PLWH are appropriate for advance care planning (ACP) and advance directives (ADs) completion. We sought to characterize AD completion among outpatient PLWH. We conducted a retrospective chart review of PLWH who receive their routine care at the University of Wisconsin HIV clinic. Data were extracted from the electronic health record. Variables were entered into a stepwise multivariate logistic regression model to assess which factors were independently associated with AD completion. Five hundred and eighty eight charts were reviewed. Eighty-one percent of subjects were male and 72% were white; mean age was 46.8 years. ADs were completed by 134 subjects and 6.7% of those were completed at the HIV clinic. In the final multivariate model, those who had completed an AD were more likely to be older than age 45; ever been diagnosed with AIDS; have cardiovascular disease, neurologic disorder, chronic kidney disease, or malignancy. In this study, a small percentage of patients had documented ADs, with only a small proportion completed in the HIV clinic. The HIV clinic is an underutilized resource to offer ACP. Interventions are needed to provide the necessary ACP resources for PLWH. C1 [Barocas, Joshua A.; Belzer, Blythe K.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI 53718 USA. [Barocas, Joshua A.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Erlandson, Kristine M.] Univ Colorado, Dept Med, Div Infect Dis, Aurora, CO USA. [Hess, Timothy; Sosman, James] Univ Wisconsin, Sch Med & Publ Hlth, Div Infect Dis, Madison, WI USA. RP Barocas, JA (reprint author), Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI 53718 USA. EM jbarocas@medicine.wisc.edu NR 48 TC 1 Z9 1 U1 2 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD MAR 4 PY 2015 VL 27 IS 3 BP 370 EP 377 DI 10.1080/09540121.2014.963019 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA CA1HI UT WOS:000348663000016 PM 25307722 ER PT J AU Park, CL Wachen, JS Kaiser, AP Stellman, JM AF Park, Crystal L. Wachen, Jennifer Schuster Kaiser, Anica Pless Stellman, Jeanne Mager TI Cumulative trauma and midlife well-being in American women who served in Vietnam: effects of combat exposure and postdeployment social support SO ANXIETY STRESS AND COPING LA English DT Article DE combat exposure; trauma; PTSD; women; perceived social support ID POSTTRAUMATIC-STRESS-DISORDER; ADVERSE CHILDHOOD EXPERIENCES; RISK-FACTORS; NATIONAL SAMPLE; MEDIATING ROLE; VETERANS; ABUSE; SYMPTOMS; WAR; LEGIONNAIRES AB Background and Objectives: Research increasingly demonstrates that trauma exposure can have cumulative effects, yet much remains to be learned about effects of cumulative trauma, particularly regarding longer term adjustment. One such trauma, combat exposure, is insufficiently understood, especially for women, who are increasingly engaged in professional combat activities. Design: The study comprised a cross-sectional survey assessing multiple aspects of current well-being in women approximately 25 years after their service in Vietnam during the Vietnam War. Methods: Participants were 1374 women (78% military and 22% nonmilitary; mean age = 59.7). This study investigated the relations between three separate categories of trauma exposure (childhood, adulthood, and combat) and well-being and examined whether perceived social support at return from Vietnam moderated the association between combat exposure and well-being. Results: While both childhood and adulthood trauma exposure related to midlife well-being, combat exposure still uniquely predicted outcomes. Further, postdeployment perceived social support moderated the association of combat and well-being: recollected higher perceived social support at homecoming buffered participants from the links between combat exposure and well-being. Conclusions: These results may have important implications for interventions to reduce the impact of traumatic experiences, particularly in light of the increasing exposure of women to direct combat events. C1 [Park, Crystal L.] Univ Connecticut, Dept Psychol, Storrs, CT 06269 USA. [Wachen, Jennifer Schuster] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. [Wachen, Jennifer Schuster; Kaiser, Anica Pless] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Kaiser, Anica Pless] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA USA. [Stellman, Jeanne Mager] Columbia Univ, Dept Hlth Policy & Management, Mailman Sch Publ Hlth, New York, NY USA. RP Park, CL (reprint author), Univ Connecticut, Dept Psychol, Storrs, CT 06269 USA. EM crystal.park@uconn.edu NR 40 TC 0 Z9 0 U1 1 U2 12 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-5806 EI 1477-2205 J9 ANXIETY STRESS COPIN JI Anxiety Stress Coping PD MAR 4 PY 2015 VL 28 IS 2 BP 144 EP 161 DI 10.1080/10615806.2014.944905 PG 18 WC Neurosciences; Psychiatry; Psychology, Multidisciplinary SC Neurosciences & Neurology; Psychiatry; Psychology GA AY6MX UT WOS:000347681400002 PM 25115369 ER PT J AU Lovejoy, J Riffe, D Lovejoy, TI AF Lovejoy, Jennette Riffe, Daniel Lovejoy, Travis I. TI An Examination of Direct and Indirect Effects of Exposure and Attention to Health Media on Intentions to Avoid Unprotected Sun Exposure SO HEALTH COMMUNICATION LA English DT Article ID COGNITIVE VARIABLES RELEVANT; PARENT-BASED INTERVENTION; SKIN-CANCER PREVENTION; UNITED-STATES; PLANNED BEHAVIOR; SUNSCREEN USE; NEWS COVERAGE; PROTECTION; ATTITUDES; ADULTS AB Skin cancer is the most commonly diagnosed cancer in the United States, accounting for more than 2 million diagnoses and more than 9,000 deaths annually. A regional online survey of students enrolled at institutions of higher education (N = 1,251) examined (a) associations between health media use and intentions to avoid unprotected sun exposure and (b) theoretically derived health behavior constructs that may mediate the relationship between media use and individuals' decisions to avoid unprotected sun exposure. Individuals with greater exposure and attention to health information in television, magazines, and newspapers had higher intentions to avoid unprotected sun exposure. Multiple mediation models indicated that health behavior constructs collectively mediated the relationship between television use and sun-protective behavioral intentions. Both cumulative and specific indirect mediating effects were observed for the relationship between magazine use and sun-protective behavioral intentions. However, the direction of effects was opposite to the hypothesized direction, due primarily to the association of magazine use with less favorable attitudes about sun protection and reduced behavioral control to avoid unprotected sun exposure. This study provides preliminary evidence for the interrelationships among media use, internal psychological states and cognitions, and health behavior decision making. Future studies should further explicate the mediating processes that account for the relationships between media and health behavior. C1 [Lovejoy, Jennette] Univ Portland, Dept Commun Studies, Portland, OR 97203 USA. [Riffe, Daniel] Univ N Carolina, Sch Journalism & Mass Commun, Chapel Hill, NC USA. [Lovejoy, Travis I.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland Vet Affairs Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR 97201 USA. RP Lovejoy, J (reprint author), Univ Portland, Dept Commun Studies, Buckley Ctr 233, 5000 N Willamette Blvd, Portland, OR 97203 USA. EM lovejoy@up.edu NR 59 TC 2 Z9 2 U1 3 U2 31 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1041-0236 EI 1532-7027 J9 HEALTH COMMUN JI Health Commun. PD MAR 4 PY 2015 VL 30 IS 3 BP 261 EP 270 DI 10.1080/10410236.2013.842526 PG 10 WC Communication; Health Policy & Services SC Communication; Health Care Sciences & Services GA AW9NZ UT WOS:000346585600006 PM 24597527 ER PT J AU Cao, Y Keum, NN Chan, AT Fuchs, CS Wu, K Giovannucci, EL AF Cao, Y. Keum, N. N. Chan, A. T. Fuchs, C. S. Wu, K. Giovannucci, E. L. TI Television watching and risk of colorectal adenoma SO BRITISH JOURNAL OF CANCER LA English DT Article DE colorectal adenoma; sedentary behaviour; television watching ID TYPE-2 DIABETES-MELLITUS; INTENSITY PHYSICAL-ACTIVITY; ALL-CAUSE MORTALITY; BODY-MASS INDEX; COLON-CANCER; CARDIOVASCULAR-DISEASE; SEDENTARY BEHAVIOR; METABOLIC SYNDROME; RECTAL-CANCER; MICROSATELLITE INSTABILITY AB Background: Prolonged TV watching, a major sedentary behaviour, is associated with increased risk of obesity and diabetes and may involve in colorectal carcinogenesis. Methods: We conducted a cross-sectional analysis among 31 065 men with >= 1 endoscopy in the Health Professionals Follow-up Study (1988-2008) to evaluate sitting while watching TV and its joint influence with leisure-time physical activity on risk of colorectal adenoma. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Prolonged sitting while watching TV was significantly associated with increased risk of colorectal adenoma (n = 4280), and adjusting for physical activity or a potential mediator body mass index did not change the estimates. The ORs (95% CIs) across categories of TV watching (0-6, 7-13, 14-20, and 21 + h per week) were 1.00 (referent), 1.09 (1.01-1.17), 1.16 (1.06-1.27), and 1.10 (0.97-1.25) (OR per 14-h per week increment = 1.11; 95% CI: 1.04-1.18; P-trend = 0.001). Compared with the least sedentary (0-6 h per week of TV) and most physically active (highest quintile) men, the most sedentary (14 + h per week) and least active (lowest quintile) men had a significant increased risk of adenoma (OR = 1.25; 95% CI: 1.05-1.49), particularly for high-risk adenoma. Conclusions: Prolonged TV viewing is associated with modest increased risk of colorectal adenoma independent of leisure-time physical activity and minimally mediated by obesity. C1 [Cao, Y.; Keum, N. N.; Wu, K.; Giovannucci, E. L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chan, A. T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, A. T.; Fuchs, C. S.; Giovannucci, E. L.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Chan, A. T.; Fuchs, C. S.; Giovannucci, E. L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Fuchs, C. S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Giovannucci, E. L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Giovannucci, EL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM egiovann@hsph.harvard.edu FU NIH [P01 CA87969, P01 CA55075, 1UM1 CA167552, R01 CA137178, K24 DK098311]; Entertainment Industry Foundation through the National Colorectal Cancer Research Alliance FX We thank the participants and staff of the Health Professionals Follow-Up Study for their valuable contributions as well as the following state cancer 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, and WY. This work was supported by grants from the NIH (P01 CA87969 to Dr Meir Stampfer; P01 CA55075 and 1UM1 CA167552 to Dr Walter Willett; R01 CA137178 and K24 DK098311 to Dr Andrew Chan) and the Entertainment Industry Foundation through the National Colorectal Cancer Research Alliance. Dr Chan is a Damon Runyon Clinical Investigator. NR 57 TC 1 Z9 1 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD MAR 3 PY 2015 VL 112 IS 5 BP 934 EP 942 DI 10.1038/bjc.2014.655 PG 9 WC Oncology SC Oncology GA CD8ZH UT WOS:000351384800020 PM 25590667 ER PT J AU Shyh-Chang, N Daley, GQ AF Shyh-Chang, Ng Daley, George Q. TI Metabolic Switches Linked to Pluripotency and Embryonic Stem Cell Differentiation SO CELL METABOLISM LA English DT Editorial Material AB Embryonic stem cells (ESCs) manifest a unique metabolism that is intimately linked to their pluripotent state. In this issue, Moussaieff et al. (2015) find that ESCs utilize glycolysis to fuel high rates of cytosolic acetyl-CoA synthesis to maintain the histone acetylation required for pluripotency. C1 [Shyh-Chang, Ng] Genome Inst Singapore, Agcy Sci Technol & Res, Singapore 138672, Singapore. [Daley, George Q.] Boston Childrens Hosp, Stem Cell Transplantat Program, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Daley, George Q.] Harvard Stem Cell Inst, Boston, MA 02115 USA. [Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Daley, George Q.] Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Boston Childrens Hosp, Stem Cell Transplantat Program, Div Pediat Hematol Oncol, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu OI Shyh-Chang, Ng/0000-0003-3138-9525 FU Howard Hughes Medical Institute NR 9 TC 9 Z9 10 U1 1 U2 14 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 MAR 3 PY 2015 VL 21 IS 3 BP 349 EP 350 DI 10.1016/j.cmet.2015.02.011 PG 2 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA CD1ZI UT WOS:000350872800001 PM 25738450 ER PT J AU Rannikmae, K Davies, G Thomson, PA Bevan, S Devan, WJ Falcone, GJ Traylor, M Anderson, CD Battey, TWK Radmanesh, F Deka, R Woo, JG Martin, LJ Jimenez-Conde, J Selim, M Brown, DL Silliman, SL Kidwell, CS Montaner, J Langefeld, CD Slowik, A Hansen, BM Lindgren, AG Meschia, JF Fornage, M Bis, JC Debette, S Ikram, MA Longstreth, WT Schmidt, R Zhang, CR Yang, Q Sharma, P Kittner, SJ Mitchell, BD Holliday, EG Levi, CR Attia, J Rothwell, PM Poole, DL Boncoraglio, GB Psaty, BM Malik, R Rost, N Worrall, BB Dichgans, M Van Agtmael, T Woo, D Markus, HS Seshadri, S Rosand, J Sudlow, CLM AF Rannikmaee, Kristiina Davies, Gail Thomson, Pippa A. Bevan, Steve Devan, William J. Falcone, Guido J. Traylor, Matthew Anderson, Christopher D. Battey, Thomas W. K. Radmanesh, Farid Deka, Ranjan Woo, Jessica G. Martin, Lisa J. Jimenez-Conde, Jordi Selim, Magdy Brown, Devin L. Silliman, Scott L. Kidwell, Chelsea S. Montaner, Joan Langefeld, Carl D. Slowik, Agnieszka Hansen, Bjoern M. Lindgren, Arne G. Meschia, James F. Fornage, Myriam Bis, Joshua C. Debette, Stephanie Ikram, Mohammad A. Longstreth, Will T. Schmidt, Reinhold Zhang, Cathy R. Yang, Qiong Sharma, Pankaj Kittner, Steven J. Mitchell, Braxton D. Holliday, Elizabeth G. Levi, Christopher R. Attia, John Rothwell, Peter M. Poole, Deborah L. Boncoraglio, Giorgio B. Psaty, Bruce M. Malik, Rainer Rost, Natalia Worrall, Bradford B. Dichgans, Martin Van Agtmael, Tom Woo, Daniel Markus, Hugh S. Seshadri, Sudha Rosand, Jonathan Sudlow, Cathie L. M. CA METASTROKE Consortium CHARGE WMH Grp ISGC ICH GWAS Study Collaborat WMH Ischemic Stroke GWAS Study Int Stroke Genetics Consortium TI Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease SO NEUROLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; MATTER HYPERINTENSITY VOLUME; MULTIPLE TESTING CORRECTION; INTRACEREBRAL HEMORRHAGE; ISCHEMIC-STROKE; NYHOLTS PROCEDURE; COL4A1 MUTATIONS; RISK-FACTORS; COLLAGEN-IV; METAANALYSIS AB Objectives:We hypothesized that common variants in the collagen genes COL4A1/COL4A2 are associated with sporadic forms of cerebral small vessel disease.Methods:We conducted meta-analyses of existing genotype data among individuals of European ancestry to determine associations of 1,070 common single nucleotide polymorphisms (SNPs) in the COL4A1/COL4A2 genomic region with the following: intracerebral hemorrhage and its subtypes (deep, lobar) (1,545 cases, 1,485 controls); ischemic stroke and its subtypes (cardioembolic, large vessel disease, lacunar) (12,389 cases, 62,004 controls); and white matter hyperintensities (2,733 individuals with ischemic stroke and 9,361 from population-based cohorts with brain MRI data). We calculated a statistical significance threshold that accounted for multiple testing and linkage disequilibrium between SNPs (p < 0.000084).Results:Three intronic SNPs in COL4A2 were significantly associated with deep intracerebral hemorrhage (lead SNP odds ratio [OR] 1.29, 95% confidence interval [CI] 1.14-1.46, p = 0.00003; r(2) > 0.9 between SNPs). Although SNPs associated with deep intracerebral hemorrhage did not reach our significance threshold for association with lacunar ischemic stroke (lead SNP OR 1.10, 95% CI 1.03-1.18, p = 0.0073), and with white matter hyperintensity volume in symptomatic ischemic stroke patients (lead SNP OR 1.07, 95% CI 1.01-1.13, p = 0.016), the direction of association was the same. There was no convincing evidence of association with white matter hyperintensities in population-based studies or with non-small vessel disease cerebrovascular phenotypes.Conclusions:Our results indicate an association between common variation in the COL4A2 gene and symptomatic small vessel disease, particularly deep intracerebral hemorrhage. These findings merit replication studies, including in ethnic groups of non-European ancestry. C1 [Rannikmaee, Kristiina; Sudlow, Cathie L. M.] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh EH8 9YL, Midlothian, Scotland. [Davies, Gail] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland. [Davies, Gail] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland. [Thomson, Pippa A.; Sudlow, Cathie L. M.] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh EH8 9YL, Midlothian, Scotland. [Bevan, Steve; Traylor, Matthew; Markus, Hugh S.] Univ Cambridge, Clin Neurosci, Cambridge CB2 1TN, England. [Devan, William J.; Falcone, Guido J.; Anderson, Christopher D.; Battey, Thomas W. K.; Radmanesh, Farid; Zhang, Cathy R.; Rost, Natalia; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Falcone, Guido J.; Anderson, Christopher D.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Falcone, Guido J.; Anderson, Christopher D.; Battey, Thomas W. K.; Radmanesh, Farid; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Deka, Ranjan] Univ Cincinnati, Coll Med, Dept Environm Hlth, Cincinnati, OH 45221 USA. [Woo, Jessica G.] Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, Cincinnati, OH 45229 USA. [Martin, Lisa J.] Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA. [Jimenez-Conde, Jordi] Univ Autonoma Barcelona, Dept Neurol, Neurovascular Res Unit, E-08193 Barcelona, Spain. [Jimenez-Conde, Jordi] Univ Autonoma Barcelona, IMIM Inst Hosp Mar Invest Med, Cardiovasc Epidemiol & Genet Res Grp, E-08193 Barcelona, Spain. [Selim, Magdy] Beth Israel Deaconess Med Ctr, Dept Neurol, Stroke Div, Boston, MA 02215 USA. [Brown, Devin L.] Univ Michigan Hlth Syst, Dept Neurol, Stroke Program, Ann Arbor, MI USA. [Silliman, Scott L.] Univ Florida, Coll Med, Dept Neurol, Jacksonville, FL USA. [Kidwell, Chelsea S.] Univ Arizona, Dept Neurol, Tucson, AZ USA. [Montaner, Joan] Univ Autonoma Barcelona, Hosp Vall dHebron, Inst Recerca, Neurovasc Res Lab, E-08193 Barcelona, Spain. [Montaner, Joan] Univ Autonoma Barcelona, Hosp Vall dHebron, Inst Recerca, Neurovasc Unit, E-08193 Barcelona, Spain. [Langefeld, Carl D.] Wake Forest Univ, Ctr Publ Hlth Genom, Winston Salem, NC 27109 USA. [Langefeld, Carl D.] Wake Forest Univ, Dept Biostat Sci, Winston Salem, NC 27109 USA. [Slowik, Agnieszka] Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland. [Hansen, Bjoern M.; Lindgren, Arne G.] Lund Univ, Dept Clin Sci Lund, Neurol, Lund, Sweden. [Hansen, Bjoern M.; Lindgren, Arne G.] Skane Univ Hosp, Dept Neurol, Lund, Sweden. [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77030 USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Epidemiol, Ctr Human Genet, Houston, TX 77030 USA. [Bis, Joshua C.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Bis, Joshua C.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Longstreth, Will T.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Longstreth, Will T.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Debette, Stephanie; Yang, Qiong; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Debette, Stephanie] Univ Paris 07, Lariboisiere Hosp, Dept Neurol, F-75221 Paris 05, France. [Debette, Stephanie] Bordeaux Univ, INSERM, UMR897, Bordeaux, France. [Ikram, Mohammad A.] Erasmus MC Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Ikram, Mohammad A.] Erasmus MC Univ Med Ctr, Dept Radiol, Rotterdam, Netherlands. [Ikram, Mohammad A.] Erasmus MC Univ Med Ctr, Dept Neurol, Rotterdam, Netherlands. [Ikram, Mohammad A.] Netherlands Consortium Hlth Aging, Amsterdam, Netherlands. [Schmidt, Reinhold] Med Univ Graz, Dept Neurol, Graz, Austria. [Sharma, Pankaj] Univ London ICR2UL, Inst Cardiovasc Res, London, England. [Sharma, Pankaj] Ashford & St Peters Hosp, London, England. [Kittner, Steven J.] Vet Affairs Med Ctr, Dept Neurol, Baltimore, MD USA. [Kittner, Steven J.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Holliday, Elizabeth G.; Attia, John] Univ Newcastle, Ctr Clin Epidemiol & Biostat, Callaghan, NSW 2308, Australia. [Levi, Christopher R.] Univ Newcastle, Ctr Translat Neurosci & Mental Hlth Res, Callaghan, NSW 2308, Australia. [Levi, Christopher R.] Hunter Med Res Inst, New Lambton, Australia. [Rothwell, Peter M.; Poole, Deborah L.] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci, Stroke Prevent Res Unit, Oxford OX3 9DU, England. [Boncoraglio, Giorgio B.] Fdn IRCCS Ist Neurol Carlo Besta, Dept Cerebrovasc Dis, Milan, Italy. [Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Grp Hlth, Res Inst, Seattle, WA USA. [Malik, Rainer; Dichgans, Martin] Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany. [Worrall, Bradford B.] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Worrall, Bradford B.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Dichgans, Martin] Munich Cluster Syst Neurol SyNergy, Munich, Germany. [Van Agtmael, Tom] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8QQ, Lanark, Scotland. [Woo, Daniel] Univ Cincinnati, Dept Neurol & Rehabil Med, Cincinnati, OH 45221 USA. RP Sudlow, CLM (reprint author), Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh EH8 9YL, Midlothian, Scotland. EM cathie.sudlow@e.ac.uk RI Boncoraglio, Giorgio/B-8647-2011; Martin, Lisa/E-2425-2016; JIMENEZ-CONDE, JORDI/C-1941-2012; IBIS, NEUROVASCULAR/O-1855-2015; Falcone, Guido/L-2287-2016; Montaner, Joan/D-3063-2015; OI Mitchell, Braxton/0000-0003-4920-4744; Martin, Lisa/0000-0001-8702-9946; Falcone, Guido/0000-0002-6407-0302; Ikram, Mohammad Arfan/0000-0003-0372-8585; Traylor, Matthew/0000-0001-6624-8621; Bevan, Steve/0000-0003-0490-6830; Anderson, Christopher/0000-0002-0053-2002; Van Agtmael, Tom/0000-0003-4282-449X; Hansen, Bjorn/0000-0001-8661-9063; Seshadri, Sudha/0000-0001-6135-2622 FU Edinburgh and Lothians Health Foundation REMIND Fund; Stroke Research and Amenities Endowments Fund; Scottish Funding Council; University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative [MR/K026992/1]; BBSRC; Medical Research Council (MSRC); Kidney Research UK [RP19/2012]; Fondation Leducq (Transatlantic Network of Excellence on the Pathogenesis of Small Vessel Disease of the Brain); NIH/National Institute of Neurological Disorders and Stroke (NINDS) [P50NS061343]; American Brain Foundation Clinical Research Training Fellowship; NIH/NINDS [K23NS086873, R01NS059727]; Massachusetts General Hospital Institute for Heart, Vascular, and Stroke Care SPARK award FX Kristiina Rannikmae is supported by the Edinburgh and Lothians Health Foundation REMIND Fund and Stroke Research and Amenities Endowments Fund. Cathie Sudlow is supported by the Scottish Funding Council. Gail Davies is supported by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1), BBSRC, and Medical Research Council (MSRC). Tom Van Agtmael is supported by the Kidney Research UK project grant RP19/2012. Details of funding for the studies contributing to the ICH GWAS can be found in reference 4. Details of funding for the studies contributing to the ischaemic stroke GWAS can be found in reference 2. Details of funding for the studies contributing to the WMH in ischaemic stroke GWAS can be found in reference 11. Details of funding for the studies contributing to the WMH in population GWAS can be found in reference 3. Martin Dichgans is supported by the Fondation Leducq (Transatlantic Network of Excellence on the Pathogenesis of Small Vessel Disease of the Brain). Guido J. Falcone is supported by the NIH/National Institute of Neurological Disorders and Stroke (NINDS) grant P50NS061343. Chistopher D. Anderson is supported by the American Brain Foundation Clinical Research Training Fellowship, NIH/NINDS K23NS086873, and Massachusetts General Hospital Institute for Heart, Vascular, and Stroke Care SPARK award. Jonathan Rosand is supported by the NIH/NINDS grant R01NS059727. NR 36 TC 13 Z9 14 U1 1 U2 15 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 MAR 3 PY 2015 VL 84 IS 9 BP 918 EP 926 DI 10.1212/WNL.0000000000001309 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CC7VO UT WOS:000350576700015 PM 25653287 ER PT J AU Utheim, O Islam, R Lyberg, T Roald, B Eidet, JR de la Paz, MF Dartt, DA Raeder, S Utheim, TP AF Utheim, Oeygunn Islam, Rakibul Lyberg, Torstein Roald, Borghild Eidet, Jon Roger Fideliz de la Paz, Maria Dartt, Darlene A. Raeder, Sten Utheim, Tor Paaske TI Serum-Free and Xenobiotic-Free Preservation of Cultured Human Limbal Epithelial Cells SO PLOS ONE LA English DT Article ID DENUDED AMNIOTIC MEMBRANE; EX-VIVO EXPANSION; FETAL CALF SERUM; STEM-CELLS; CORNEAL EPITHELIUM; SUSPENSION CULTURE; FEEDER LAYER; TRANSPLANTATION; EXPRESSION; PHENOTYPE AB Aim/Purpose of the Study To develop a one-week storage method, without serum and xenobiotics, that would maintain cell viability, morphology, and phenotype of cultured human limbal epithelial sheets. Materials and Methods Human limbal explants were cultured on intact human amniotic membranes for two weeks. The sheets were stored in a hermetically sealed container at 23 degrees C in either a serum-free medium with selected animal serum-derived compounds (Quantum 286) or a xenobioticfree medium (Minimal Essential Medium) for 4 and 7 days. Stored and non-stored cultures were analyzed for cell viability, amniotic membrane and epithelial sheet thickness, and a panel of immunohistochemical markers for immature cells (Delta Np63 alpha, p63, Bmi-1, C/EBP partial derivative, ABCG2 and K19), differentiated cells (K3 and Cx43), proliferation (PCNA), and apoptosis (Caspase-3). Results The cell viability of the cultures was 98 +/- 1% and remained high after storage. Mean central thickness of non-stored limbal epithelial sheets was 23 +/- 3 mu m, and no substantial loss of cells was observed after storage. The non-stored epithelial sheets expressed a predominantly immature phenotype with Delta Np63a positivity of more than 3% in 9 of 13 cultures. After storage, the expression of ABCG2 and C/EBP partial derivative was reduced for the 7 day Quantum 286-storage group; (P = 0.04), and Bmi1 was reduced after 4 day Quantum 286-storage; (P = 0.02). No other markers varied significantly. The expression of differentiation markers was unrelated to the thickness of the epithelia and amnioticmembrane, apart from ABCG2, which correlated negatively with thickness of limbal epithelia (R = -0.69, P = 0.01) and Delta Np63 alpha, which correlated negatively with amniotic membrane thickness (R = -0.59, P = 0.03). Conclusion Limbal epithelial cells cultured from explants on amniotic membrane can be stored at 23 degrees C in both serum-free and xenobiotic-free media, with sustained cell viability, ultrastructure, and Delta Np63 alpha-positivity after both 4 and 7 days. C1 [Utheim, Oeygunn; Islam, Rakibul; Lyberg, Torstein; Eidet, Jon Roger; Utheim, Tor Paaske] Oslo Univ Hosp, Dept Med Biochem, Oslo, Norway. [Utheim, Oeygunn; Utheim, Tor Paaske] Oslo Univ Hosp, Dept Ophthalmol, Oslo, Norway. [Islam, Rakibul; Utheim, Tor Paaske] Univ Oslo, Fac Dent, Dept Oral Biol, Oslo, Norway. [Roald, Borghild] Oslo Univ Hosp, Dept Pathol, Oslo, Norway. [Fideliz de la Paz, Maria] Univ Autonoma Barcelona, Inst Univ Barraquer, E-08193 Barcelona, Spain. [Dartt, Darlene A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA USA. [Raeder, Sten] Norwegian Dry Eye Clin, Oslo, Norway. RP Utheim, O (reprint author), Oslo Univ Hosp, Dept Med Biochem, Oslo, Norway. EM utheim2@gmail.com FU South-Eastern Norway Regional Health Authority [2010092] FX The research was funded by the South-Eastern Norway Regional Health Authority, grant number 2010092, project name "Treating blindness using novel tissue storage technology", url http://forskningsprosjekter.ihelse.net/visningprosjektrapport.aspx?repor tId=7593 and http://www.helse-sorost.no/omoss_/english. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 0 Z9 0 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 3 PY 2015 VL 10 IS 3 AR e0118517 DI 10.1371/journal.pone.0118517 PG 23 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CC4HV UT WOS:000350314700036 PM 25734654 ER PT J AU Levy, O Mortensen, LJ Boquet, G Tong, ZX Perrault, C Benhamou, B Zhang, JD Stratton, T Han, E Safaee, H Musabeyezu, J Yang, ZJ Multon, MC Rothblatt, J Deleuze, JF Lin, CP Karp, JM AF Levy, Oren Mortensen, Luke J. Boquet, Gerald Tong, Zhixiang Perrault, Christelle Benhamou, Brigitte Zhang, Jidong Stratton, Tara Han, Edward Safaee, Helia Musabeyezu, Juliet Yang, Zijiang Multon, Marie-Christine Rothblatt, Jonathan Deleuze, Jean-Francois Lin, Charles P. Karp, Jeffrey M. TI A Small-Molecule Screen for Enhanced Homing of Systemically Infused Cells SO CELL REPORTS LA English DT Article ID MESENCHYMAL STEM-CELLS; ENDOTHELIAL-CELLS; KINASE; EXPRESSION; ADHESION; BONE; RUBOXISTAURIN; INFLAMMATION; ACTIVATION; INHIBITOR AB Poor homing of systemically infused cells to disease sites may limit the success of exogenous cell-based therapy. In this study, we screened 9,000 signal-transduction modulators to identify hits that increase mesenchymal stromal cell (MSC) surface expression of homing ligands that bind to intercellular adhesion molecule 1 (ICAM-1), such as CD11a. Pretreatment of MSCs with Ro-31-8425, an identified hit from this screen, increased MSC firm adhesion to an ICAM-1-coated substrate in vitro and enabled targeted delivery of systemically administered MSCs to inflamed sites in vivo in a CD11a- (and other ICAM-1-binding domains)-dependent manner. This resulted in a heightened anti-inflammatory response. This represents a new strategy for engineering cell homing to enhance therapeutic efficacy and validates CD11a and ICAM-1 as potential targets. Altogether, this multi-step screening process may significantly improve clinical outcomes of cell-based therapies. C1 [Levy, Oren; Tong, Zhixiang; Han, Edward; Safaee, Helia; Musabeyezu, Juliet; Yang, Zijiang; Karp, Jeffrey M.] Harvard Univ, Brigham & Womens Hosp, Ctr Regenerat Therapeut, Div Biomed Engn,Dept Med,Med Sch, Cambridge, MA 02139 USA. [Levy, Oren; Mortensen, Luke J.; Tong, Zhixiang; Stratton, Tara; Han, Edward; Safaee, Helia; Musabeyezu, Juliet; Yang, Zijiang; Lin, Charles P.; Karp, Jeffrey M.] Harvard Stem Cell Inst, Cambridge, MA 02139 USA. [Levy, Oren; Tong, Zhixiang; Han, Edward; Safaee, Helia; Musabeyezu, Juliet; Yang, Zijiang; Karp, Jeffrey M.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Mortensen, Luke J.; Stratton, Tara; Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Mortensen, Luke J.; Stratton, Tara; Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Boquet, Gerald; Perrault, Christelle; Benhamou, Brigitte; Zhang, Jidong; Multon, Marie-Christine; Deleuze, Jean-Francois] Sanofi R&D, Ctr Rech Vitry Alfortville, F-94403 Vitry Sur Seine, France. [Rothblatt, Jonathan] Sanofi R&D, Cambridge, MA 02139 USA. RP Lin, CP (reprint author), Harvard Stem Cell Inst, Cambridge, MA 02139 USA. EM lin@helix.mgh.harvard.edu; jeffkarp.bwh@gmail.com RI Tong, Zhixiang/G-5685-2016; OI Mortensen, Luke/0000-0002-4331-4099 FU Sanofi-Aventis U.S.; National Institutes of Health [HL095722, P41 EB015903-02S1] FX The authors wish to thank Sophie Fontaine and Celine Chansac from Sanofi for their technical support. This work was supported by a research grant from Sanofi-Aventis U.S. to J.M.K. and C.P.L. and by National Institutes of Health grants HL095722 (to J.M.K.) and P41 EB015903-02S1 (to C.P.L.). G.B., C.P., B.B., J.Z., M.C., and J.R. are employed by Sanofi. J.M.K. consults in the field of cell therapy for Stempeutics, Sanofi, and Mesoblast. NR 26 TC 9 Z9 9 U1 0 U2 9 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 MAR 3 PY 2015 VL 10 IS 8 BP 1261 EP 1268 DI 10.1016/j.celrep.2015.01.057 PG 8 WC Cell Biology SC Cell Biology GA CC7QW UT WOS:000350564200004 PM 25732817 ER PT J AU Wurtz, P Havulinna, AS Soininen, P Tynkkynen, T Prieto-Merino, D Tillin, T Ghorbani, A Artati, A Wang, Q Tiainen, M Kangas, AJ Kettunen, J Kaikkonen, J Mikkila, V Jula, A Kahonen, M Lehtimaki, T Lawlor, DA Gaunt, TR Hughes, AD Sattar, N Illig, T Adamski, J Wang, TJ Perola, M Ripatti, S Vasan, RS Raitakari, OT Gerszten, RE Casas, JP Chaturvedi, N Ala-Korpela, M Salomaa, V AF Wurtz, Peter Havulinna, Aki S. Soininen, Pasi Tynkkynen, Tuulia Prieto-Merino, David Tillin, Therese Ghorbani, Anahita Artati, Anna Wang, Qin Tiainen, Mika Kangas, Antti J. Kettunen, Johannes Kaikkonen, Jari Mikkila, Vera Jula, Antti Kahonen, Mika Lehtimaki, Terho Lawlor, Debbie A. Gaunt, Tom R. Hughes, Alun D. Sattar, Naveed Illig, Thomas Adamski, Jerzy Wang, Thomas J. Perola, Markus Ripatti, Samuli Vasan, Ramachandran S. Raitakari, Olli T. Gerszten, Robert E. Casas, Juan-Pablo Chaturvedi, Nish Ala-Korpela, Mika Salomaa, Veikko TI Metabolite Profiling and Cardiovascular Event Risk A Prospective Study of 3 Population-Based Cohorts SO CIRCULATION LA English DT Article DE amino acids; biological markers; fatty acids; metabolomics; risk factors ID MONOUNSATURATED FATTY-ACIDS; HOSPITAL DISCHARGE REGISTER; CORONARY-HEART-DISEASE; YOUNG FINNS; SUBCLINICAL ATHEROSCLEROSIS; ASSOCIATION; BIOMARKERS; EPIDEMIOLOGY; METABOLOMICS; PREDICTION AB Background-High-throughput profiling of circulating metabolites may improve cardiovascular risk prediction over established risk factors. Methods and Results-We applied quantitative nuclear magnetic resonance metabolomics to identify the biomarkers for incident cardiovascular disease during long-term follow-up. Biomarker discovery was conducted in the National Finnish FINRISK study (n = 7256; 800 events). Replication and incremental risk prediction was assessed in the Southall and Brent Revisited (SABRE) study (n = 2622; 573 events) and British Women's Health and Heart Study (n = 3563; 368 events). In targeted analyses of 68 lipids and metabolites, 33 measures were associated with incident cardiovascular events at P < 0.0007 after adjusting for age, sex, blood pressure, smoking, diabetes mellitus, and medication. When further adjusting for routine lipids, 4 metabolites were associated with future cardiovascular events in meta-analyses: higher serum phenylalanine (hazard ratio per standard deviation, 1.18; 95% confidence interval, 1.12-1.24; P = 4x10(-10)) and monounsaturated fatty acid levels (1.17; 1.11-1.24; P = 1x10(-8)) were associated with increased cardiovascular risk, while higher omega-6 fatty acids (0.89; 0.84-0.94; P = 6x10(-5)) and docosahexaenoic acid levels (0.90; 0.86-0.95; P = 5x10(-5)) were associated with lower risk. A risk score incorporating these 4 biomarkers was derived in FINRISK. Risk prediction estimates were more accurate in the 2 validation cohorts (relative integrated discrimination improvement, 8.8% and 4.3%), albeit discrimination was not enhanced. Risk classification was particularly improved for persons in the 5% to 10% risk range (net reclassification, 27.1% and 15.5%). Biomarker associations were further corroborated with mass spectrometry in FINRISK (n = 671) and the Framingham Offspring Study (n = 2289). Conclusions-Metabolite profiling in large prospective cohorts identified phenylalanine, monounsaturated fatty acids, and polyunsaturated fatty acids as biomarkers for cardiovascular risk. This study substantiates the value of high-throughput metabolomics for biomarker discovery and improved risk assessment. C1 [Wurtz, Peter; Soininen, Pasi; Tynkkynen, Tuulia; Wang, Qin; Tiainen, Mika; Kangas, Antti J.; Kettunen, Johannes; Ala-Korpela, Mika] Univ Oulu, Inst Hlth Sci, Oulu 90014, Finland. [Wurtz, Peter; Havulinna, Aki S.; Kettunen, Johannes; Jula, Antti; Perola, Markus; Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Oulu, Finland. [Wurtz, Peter; Havulinna, Aki S.; Perola, Markus; Ripatti, Samuli] Univ Helsinki, Inst Mol Med Finland, FIN-00014 Helsinki, Finland. [Wurtz, Peter; Tynkkynen, Tuulia; Wang, Qin; Tiainen, Mika; Ala-Korpela, Mika] Univ Eastern Finland, Sch Pharm, NMR Metab Lab, Kuopio, Finland. [Prieto-Merino, David; Casas, Juan-Pablo] Univ London London Sch Hyg & Trop Med, Fac Epidemiol & Publ Hlth, London WC1E 7HT, England. [Tillin, Therese; Hughes, Alun D.; Casas, Juan-Pablo; Chaturvedi, Nish] UCL, Inst Cardiovasc Sci, London WC1E 6BT, England. [Ghorbani, Anahita; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Ghorbani, Anahita; Vasan, Ramachandran S.] Boston Univ, Sch Med, Framingham, MA USA. [Artati, Anna; Adamski, Jerzy] Helmholtz Zentrum Munchen, Inst Expt Genet, Genome Anal Ctr, Neuherberg, Germany. [Kaikkonen, Jari; Mikkila, Vera; Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, SF-20500 Turku, Finland. [Mikkila, Vera] Univ Helsinki, Dept Food & Environm Sci, FIN-00014 Helsinki, Finland. [Kahonen, Mika] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland. [Kahonen, Mika] Tampere Univ Hosp, Tampere, Finland. [Lehtimaki, Terho] Univ Tampere, Fimlab Labs, Dept Clin Chem, FIN-33101 Tampere, Finland. [Lehtimaki, Terho] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Lawlor, Debbie A.; Gaunt, Tom R.; Ala-Korpela, Mika] Univ Bristol, MRC, Integrat Epidemiol Unit, Bristol BS8 1TH, Avon, England. [Lawlor, Debbie A.; Gaunt, Tom R.; Ala-Korpela, Mika] Univ Bristol, Sch Social & Community Med, Bristol BS8 1TH, Avon, England. [Sattar, Naveed] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8QQ, Lanark, Scotland. [Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany. [Illig, Thomas] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany. [Adamski, Jerzy] German Ctr Diabet Res, Neuherberg, Germany. [Adamski, Jerzy] Tech Univ Munich, Freising Weihenstephan, Germany. [Wang, Thomas J.; Gerszten, Robert E.] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. [Wang, Thomas J.; Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Wang, Thomas J.] Vanderbilt Univ, Div Cardiol, Nashville, TN 37232 USA. [Ripatti, Samuli] Univ Helsinki, Hjelt Inst, FIN-00014 Helsinki, Finland. [Ripatti, Samuli] Wellcome Trust Sanger Inst, Hinxton, England. [Vasan, Ramachandran S.] Boston Univ, Sect Prevent Med & Epidemiol, Boston, MA 02215 USA. [Vasan, Ramachandran S.] Boston Univ, Cardiol Sect, Dept Med, Boston, MA 02215 USA. [Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland. [Gerszten, Robert E.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Ala-Korpela, Mika] Oulu Univ Hosp, Oulu, Finland. RP Wurtz, P (reprint author), Univ Oulu, Inst Hlth Sci, Aapistie 5A,POB 5000, Oulu 90014, Finland. EM peter.wurtz@computationalmedicine.fi RI Ripatti, Samuli/H-9446-2014; OI Ripatti, Samuli/0000-0002-0504-1202; Tynkkynen, Tuulia/0000-0002-8586-7345; Wurtz, Peter/0000-0002-5832-0221; Ramachandran, Vasan/0000-0001-7357-5970; Lawlor, Debbie A/0000-0002-6793-2262; Prieto-Merino, David/0000-0001-5001-0061; Gaunt, Tom/0000-0003-0924-3247 FU Academy of Finland [139635, 137870, 250422, 251217, 266199]; European Commission Seventh Framework Programme [BioSHaRE 261433]; Sigrid Juselius Foundation; Yrjo Jahnsson Foundation; Emil Aaltonen Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Medical Research Fund of Tampere; UK Medical Research Council via the University of Bristol Integrative Epidemiology Unit (IEU) [MC_UU_12013/5]; University of Oulu, Finland; Wellcome Trust [WT082464AIA]; British Heart Foundation [SP/07/001/23603]; Diabetes UK [13/0004774]; UK Department of Health Policy Research Programme - UK Medical Research Council [G1000427]; US National Institutes of Health [R01 DK 081572, R01 HL98280]; NHLBI [N01-HC-25195] FX This study was supported by the Academy of Finland (139635, 137870, 250422, 251217, 266199), the European Commission Seventh Framework Programme (BioSHaRE 261433), the Sigrid Juselius Foundation, the Yrjo Jahnsson Foundation, the Emil Aaltonen Foundation, the Paavo Nurmi Foundation, the Finnish Foundation for Cardiovascular Research, the Medical Research Fund of Tampere, the UK Medical Research Council via the University of Bristol Integrative Epidemiology Unit (IEU; MC_UU_12013/5), and Strategic Research Funding from the University of Oulu, Finland. The Wellcome Trust (WT082464AIA), British Heart Foundation (SP/07/001/23603) and Diabetes UK (13/0004774) support the SABRE Study. The British Women's Heart and Health Study was funded by the British Heart Foundation and UK Department of Health Policy Research Programme with metabolomics data funded by the UK Medical Research Council (G1000427). Metabolomics in the Framingham offspring study was supported by the US National Institutes of Health grants R01 DK 081572 and R01 HL98280. Surveillance of CVD in the Framingham Heart Study is supported by N01-HC-25195 (from the NHLBI). NR 57 TC 58 Z9 59 U1 5 U2 28 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 MAR 3 PY 2015 VL 131 IS 9 BP 774 EP U52 DI 10.1161/CIRCULATIONAHA.114.013116 PG 37 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CC4FY UT WOS:000350308400004 PM 25573147 ER PT J AU Yeh, RW Mauri, L Kereiakes, DJ AF Yeh, Robert W. Mauri, Laura Kereiakes, Dean J. TI Dual Antiplatelet Therapy Duration Following Coronary Stenting SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE drug-eluting stent(s); percutaneous coronary angioplasty ID DRUG-ELUTING STENTS; IMPLANTATION; TRIAL; MULTICENTER; THROMBOSIS; LONG C1 [Yeh, Robert W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Mauri, Laura] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Kereiakes, Dean J.] Christ Hosp, Lindner Res Ctr, Heart & Vasc Ctr, Cincinnati, OH 45219 USA. RP Kereiakes, DJ (reprint author), Christ Hosp, Lindner Res Ctr, Heart & Vasc Ctr, 2123 Auburn Ave,Suite 424, Cincinnati, OH 45219 USA. EM lindner@thechristhospital.com FU NHLBI NIH HHS [K23 HL118138] NR 13 TC 6 Z9 6 U1 0 U2 2 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 MAR 3 PY 2015 VL 65 IS 8 BP 787 EP 790 DI 10.1016/j.jacc.2015.01.004 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CC3AG UT WOS:000350215800004 PM 25720621 ER PT J AU Wang, GH Shi, YJ Jiang, XY Leak, RK Hu, XM Wu, Y Pu, HJ Li, WW Tang, B Wang, Y Gao, YQ Zheng, P Bennett, MVL Chen, J AF Wang, Guohua Shi, Yejie Jiang, Xiaoyan Leak, Rehana K. Hu, Xiaoming Wu, Yun Pu, Hongjian Li, Wei-Wei Tang, Bo Wang, Yun Gao, Yanqin Zheng, Ping Bennett, Michael V. L. Chen, Jun TI HDAC inhibition prevents white matter injury by modulating microglia/macrophage polarization through the GSK3 beta/PTEN/Akt axis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE traumatic brain injury; oligodendrocyte; microglial polarization; myelination; inflammation ID TRAUMATIC BRAIN-INJURY; MICROGLIA; ACTIVATION; NEUROPROTECTION; DEGENERATION; INFLAMMATION; CHALLENGES; ISCHEMIA; DYNAMICS; DAMAGE AB Severe traumatic brain injury (TBI) elicits destruction of both gray and white matter, which is exacerbated by secondary proinflammatory responses. Although white matter injury (WMI) is strongly correlated with poor neurological status, the maintenance of white matter integrity is poorly understood, and no current therapies protect both gray and white matter. One candidate approach that may fulfill this role is inhibition of class I/II histone deacetylases (HDACs). Here we demonstrate that the HDAC inhibitor Scriptaid protects white matter up to 35 d after TBI, as shown by reductions in abnormally dephosphorylated neurofilament protein, increases in myelin basic protein, anatomic preservation of myelinated axons, and improved nerve conduction. Furthermore, Scriptaid shifted microglia/macrophage polarization toward the protective M2 phenotype and mitigated inflammation. In primary cocultures of microglia and oligodendrocytes, Scriptaid increased expression of microglial glycogen synthase kinase 3 beta (GSK3 beta), which phosphorylated and inactivated phosphatase and tensin homologue (PTEN), thereby enhancing phosphatidylinositide 3-kinases (PI3K)/Akt signaling and polarizing microglia toward M2. The increase in GSK3 beta in microglia and their phenotypic switch to M2 was associated with increased preservation of neighboring oligodendrocytes. These findings are consistent with recent findings that microglial phenotypic switching modulates white matter repair and axonal remyelination and highlight a previously unexplored role for HDAC activity in this process. Furthermore, the functions of GSK3 beta may be more subtle than previously thought, in that GSK3 beta can modulate microglial functions via the PTEN/PI3K/Akt signaling pathway and preserve white matter homeostasis. Thus, inhibition of HDACs in microglia is a potential future therapy in TBI and other neurological conditions with white matter destruction. C1 [Wang, Guohua; Jiang, Xiaoyan; Pu, Hongjian; Li, Wei-Wei; Tang, Bo; Wang, Yun; Gao, Yanqin; Zheng, Ping; Chen, Jun] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China. [Wang, Guohua; Jiang, Xiaoyan; Pu, Hongjian; Li, Wei-Wei; Tang, Bo; Wang, Yun; Gao, Yanqin; Zheng, Ping; Chen, Jun] Fudan Univ, Inst Brain Sci, Shanghai 200032, Peoples R China. [Wang, Guohua; Shi, Yejie; Hu, Xiaoming; Wu, Yun; Pu, Hongjian; Gao, Yanqin; Chen, Jun] Univ Pittsburgh, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. [Shi, Yejie; Hu, Xiaoming; Wu, Yun; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. [Leak, Rehana K.] Duquesne Univ, Mylan Sch Pharm, Div Pharmaceut Sci, Pittsburgh, PA 15282 USA. [Bennett, Michael V. L.] Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Bronx, NY 10461 USA. RP Bennett, MVL (reprint author), Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Bronx, NY 10461 USA. EM michael.bennett@einstein.yu.edu; chenj2@upmc.edu RI Gao, Yanqin/I-6790-2016; OI Gao, Yanqin/0000-0002-4915-9819; Leak, Rehana/0000-0003-2817-7417 FU National Institutes of Health [NS36736, NS43802, NS45048, NS45287]; US Department of Veterans Affairs Research Career Scientist Award; Chinese Natural Science Foundation [81020108021, 81171149, 81371306, 81000497, 81471257, 81228008]; PhD Training Grant [20120071110042]; Ministry of Education of the People's Republic of China Talent Training Fellowship Grant [J1210041]; State Administration of Foreign Experts Affairs High-End Distinguished Professorship Grant [GDW20133100069]; Hillman Foundation Award FX This research was supported by National Institutes of Health Grants NS36736, NS43802, and NS45048 (to J.C.) and NS45287 (to M.V.L.B.); US Department of Veterans Affairs Research Career Scientist Award (to J.C.); Chinese Natural Science Foundation Grants 81020108021, 81171149, and 81371306 (to Y.G.), 81000497 and 81471257 (to G.W.), and 81228008 (to J.C. and P.Z.), and PhD Training Grant 20120071110042 (to J.C.); Ministry of Education of the People's Republic of China Talent Training Fellowship Grant J1210041 (to B.T.); and State Administration of Foreign Experts Affairs High-End Distinguished Professorship Grant GDW20133100069 (to M.V.L.B.). R.K.L. is supported by a Hillman Foundation Award. NR 33 TC 44 Z9 48 U1 5 U2 31 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 3 PY 2015 VL 112 IS 9 BP 2853 EP 2858 DI 10.1073/pnas.1501441112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CC3DK UT WOS:000350224900065 PM 25691750 ER PT J AU Han, HS Niemeyer, E Huang, YH Kamoun, WS Martin, JD Bhaumik, J Chen, YC Roberge, S Cui, J Martin, MR Fukumura, D Jain, RK Bawendi, MG Duda, DG AF Han, Hee-Sun Niemeyer, Elisabeth Huang, Yuhui Kamoun, Walid S. Martin, John D. Bhaumik, Jayeeta Chen, Yunching Roberge, Sylvie Cui, Jian Martin, Margaret R. Fukumura, Dai Jain, Rakesh K. Bawendi, Moungi G. Duda, Dan G. TI APPLIED BIOLOGICAL SCIENCES, CHEMISTRY (vol 112, pg 1350, 2015) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Correction C1 [Han, Hee-Sun; Cui, Jian; Bawendi, Moungi G.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Martin, John D.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Niemeyer, Elisabeth; Huang, Yuhui; Kamoun, Walid S.; Martin, John D.; Bhaumik, Jayeeta; Chen, Yunching; Roberge, Sylvie; Martin, Margaret R.; Fukumura, Dai; Jain, Rakesh K.; Duda, Dan G.] Massachusetts Gen Hosp, Edwin L Steele Lab, Boston, MA 02114 USA. [Niemeyer, Elisabeth; Huang, Yuhui; Kamoun, Walid S.; Martin, John D.; Bhaumik, Jayeeta; Chen, Yunching; Roberge, Sylvie; Martin, Margaret R.; Fukumura, Dai; Jain, Rakesh K.; Duda, Dan G.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Han, HS (reprint author), MIT, Dept Chem, Cambridge, MA 02139 USA. NR 1 TC 0 Z9 0 U1 1 U2 6 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 MAR 3 PY 2015 VL 112 IS 9 BP E1048 EP E1048 DI 10.1073/pnas.1501954112 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CC3DK UT WOS:000350224900019 ER PT J AU Pangrsic, T Gabrielaitis, M Michanski, S Schwaller, B Wolf, F Strenzke, N Moser, T AF Pangrsic, Tina Gabrielaitis, Mantas Michanski, Susann Schwaller, Beat Wolf, Fred Strenzke, Nicola Moser, Tobias TI EF-hand protein Ca2+ buffers regulate Ca2+ influx and exocytosis in sensory hair cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE calcium buffers; exocytosis; calcium current; synapse; hair cell ID AUDITORY-NERVE FIBERS; FAST-TWITCH MUSCLES; RIBBON SYNAPSE; CALCIUM-CHANNELS; CALBINDIN D-28K; TRANSMITTER RELEASE; AFFERENT SYNAPSE; CA2+-DEPENDENT INACTIVATION; PRESYNAPTIC ACTIVITY; LACKING PARVALBUMIN AB EF-hand Ca2+-binding proteins are thought to shape the spatio-temporal properties of cellular Ca2+ signaling and are prominently expressed in sensory hair cells in the ear. Here, we combined genetic disruption of parvalbumin-a, calbindin-D28k, and calretinin in mice with patch-clamp recording, in vivo physiology, and mathematical modeling to study their role in Ca2+ signaling, exocytosis, and sound encoding at the synapses of inner hair cells (IHCs). IHCs lacking all three proteins showed excessive exocytosis during prolonged depolarizations, despite enhanced Ca2+-dependent inactivation of their Ca2+ current. Exocytosis of readily releasable vesicles remained unchanged, in accordance with the estimated tight spatial coupling of Ca2+ channels and release sites (effective "coupling distance" of 17 nm). Substitution experiments with synthetic Ca2+ chelators indicated the presence of endogenous Ca2+ buffers equivalent to 1 mM synthetic Ca2+- binding sites, approximately half of them with kinetics as fast as 1,2-Bis(2-aminophenoxy) ethane N, N, N', N'-tetraacetic acid (BAPTA). Synaptic sound encoding was largely unaltered, suggesting that excess exocytosis occurs extrasynaptically. We conclude that EF-hand Ca2+ buffers regulate presynaptic IHC function for metabolically efficient sound coding. C1 [Pangrsic, Tina; Gabrielaitis, Mantas; Michanski, Susann; Moser, Tobias] Univ Med Ctr Gottingen, Inst Auditory Neurosci & InnerEarLab, D-37099 Gottingen, Germany. [Pangrsic, Tina; Michanski, Susann; Wolf, Fred; Strenzke, Nicola; Moser, Tobias] Univ Gottingen, Collaborat Res Ctr 889, D-37099 Gottingen, Germany. [Gabrielaitis, Mantas; Wolf, Fred] Max Planck Inst Dynam & Self Org, Theoret Neurophys Grp, D-37077 Gottingen, Germany. [Gabrielaitis, Mantas; Wolf, Fred; Moser, Tobias] Univ Gottingen, Bernstein Ctr Computat Neurosci, D-37077 Gottingen, Germany. [Schwaller, Beat] Univ Fribourg, Dept Med, Unit Anat, CH-1700 Fribourg, Switzerland. [Strenzke, Nicola] Univ Med Ctr Gottingen, Dept Otolaryngol, Auditory Syst Physiol Grp, InnerEarLab, D-37099 Gottingen, Germany. [Strenzke, Nicola] Harvard Univ, Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Pangrsic, T (reprint author), Univ Med Ctr Gottingen, Inst Auditory Neurosci, Synapt Physiol Mammalian Vestibular Hair Cells Jr, D-37099 Gottingen, Germany. EM tpangrs@gwdg.de; nstrenzke@med.uni-goettingen.de; tmoser@gwdg.de RI Moser, Tobias/L-5068-2014 OI Moser, Tobias/0000-0001-7145-0533 FU Humboldt fellowship; Deutsche Forschungsgemeinschaft (DFG); Collaborative Research Center 889 Projects; German Federal Ministry for Education and Research through the Bernstein Center for Computational Neuroscience [01GQ0811, 01GQ1005A] FX We thank M. Charles Liberman for providing guidance and the facilities for the single auditory nerve fiber recordings, Gerhard Hoch for providing image analysis MATLAB routines, Carolin Wichmann for providing the EM micrograph, Erwin Neher, Aaron B. Wong, and members of the InnerEarLab for discussion and comments on the manuscript, and Margitta Koppler, Sonja Blume, Christian Rudiger, Sandra Gerke, and Christiane Senger-Freitag (Institute for Auditory Neuroscience, University Medical Center Gottingen,) and Simone Eichenberger and Valerie Salicio (Unit of Anatomy, University of Fribourg) for excellent technical assistance. This work was supported by a Humboldt fellowship (to T.P.), grants of the Deutsche Forschungsgemeinschaft (DFG) through a fellowship (to N.S.) and the Collaborative Research Center 889 Projects A2, A6, and C6 (to T.M., N.S., and F.W.), and German Federal Ministry for Education and Research Grants 01GQ0811 (to F.W.) and 01GQ1005A (to T.M.) through the Bernstein Center for Computational Neuroscience. NR 73 TC 15 Z9 15 U1 1 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 3 PY 2015 VL 112 IS 9 BP E1028 EP E1037 DI 10.1073/pnas.1416424112 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CC3DK UT WOS:000350224900017 PM 25691754 ER PT J AU Haffajee, RL Jena, AB Weiner, SG AF Haffajee, Rebecca L. Jena, Anupam B. Weiner, Scott G. TI Mandatory Use of Prescription Drug Monitoring Programs SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Haffajee, Rebecca L.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02215 USA. [Haffajee, Rebecca L.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jena, Anupam B.] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Weiner, Scott G.] Brigham & Womens Hosp, Div Hlth Policy Res Translat, Dept Emergency Med, Boston, MA 02115 USA. RP Haffajee, RL (reprint author), Harvard Univ, Sch Med, Dept Populat Med, 133 Brookline Ave,Sixth Floor, Boston, MA 02215 USA. EM haffajee@fas.harvard.edu FU NIH HHS [1DP5OD017897-01, DP5 OD017897] NR 10 TC 22 Z9 23 U1 0 U2 5 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 MAR 3 PY 2015 VL 313 IS 9 BP 891 EP 892 DI 10.1001/jama.2014.18514 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CC3FN UT WOS:000350231800007 PM 25622279 ER PT J AU Darrow, KN Slama, MCC Kozie, ED Owoc, M Hancock, K Kempfle, J Edge, A Lacour, S Boyden, E Polley, D Brown, MC Lee, DJ AF Darrow, Keith N. Slama, Michael C. C. Kozie, Elliott D. Owoc, Maryanna Hancock, Kenneth Kempfle, Judith Edge, Albert Lacour, Stephanie Boyden, Edward Polley, Daniel Brown, M. Christian Lee, Daniel J. TI Optogenetic stimulation of the cochlear nucleus using channelrhodopsin-2 evokes activity in the central auditory pathways SO BRAIN RESEARCH LA English DT Article DE ChR2; Inferior colliculus; Auditory cortex; Synchronization index; Neural prosthesis ID BRAIN-STEM IMPLANT; INFERIOR COLLICULUS; TRANSGENIC MICE; OPTICAL CONTROL; NEUROFIBROMATOSIS TYPE-2; MILLISECOND-TIMESCALE; PHONEME RECOGNITION; SPEECH-PERCEPTION; NEURAL ACTIVITY; SUPERIOR OLIVE AB Optogenetics has become an important research tool and is being considered as the basis for several neural prostheses. However, few studies have applied optogenetics to the auditory brainstem. This study explored whether optical activation of the cochlear nucleus (CN) elicited responses in neurons in higher centers of the auditory pathway and whether it elicited an evoked response. Viral-mediated gene transfer was used to express channelrhodopsin-2 (ChR2) in the mouse CN. Blue light was delivered via an optical fiber placed near the surface of the infected CN and recordings were made in higher-level centers. Optical stimulation evoked excitatory multiunit spiking activity throughout the tonotopic axis of the central nucleus of the inferior colliculus (IC) and the auditory cortex (Actx). The pattern and magnitude of IC activity elicited by optical stimulation was comparable to that obtained with a 50 dB SPL acoustic click. This broad pattern of activity was consistent with histological confirmation of green fluorescent protein (GFP) label of cell bodies and axons throughout the CN. Increasing pulse rates up to 320 Hz did not significantly affect threshold or bandwidth of the IC responses, but rates higher than 50 Hz resulted in desynchronized activity. Optical stimulation also evoked an auditory brainstem response, which had a simpler waveform than the response to acoustic stimulation. Control cases showed no responses to optical stimulation. These data suggest that optogenetic control of central auditory neurons is feasible, but opsins with faster channel kinetics may be necessary to convey information at rates typical of many auditory signals. (C) 2014 Elsevier B.V. All rights reserved. C1 [Darrow, Keith N.; Owoc, Maryanna] Worcester State Univ, Dept Commun Sci & Disorders, Worcester, MA USA. [Darrow, Keith N.; Slama, Michael C. C.; Kempfle, Judith; Polley, Daniel; Brown, M. Christian] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Slama, Michael C. C.; Kozie, Elliott D.; Hancock, Kenneth; Kempfle, Judith; Edge, Albert; Polley, Daniel; Brown, M. Christian; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Kozie, Elliott D.; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Lacour, Stephanie] Ecole Polytech Fed Lausanne, IMT IBI, Ctr Neuroprosthet, Lab Soft Bioelect Interfaces, Lausanne, Switzerland. [Boyden, Edward] MIT, Media Lab, Dept Brain & Cognit Sci & Biol Engn, Cambridge, MA 02139 USA. [Boyden, Edward] MIT, McGovern Inst, Cambridge, MA 02139 USA. RP Lee, DJ (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Daniel_Lee@meei.harvard.edu RI Lacour, Stephanie/E-6375-2010; Kozin, Elliott/J-1225-2014; OI Kozin, Elliott/0000-0002-0305-0682; Polley, Daniel/0000-0002-5120-2409 FU Fondation Bertarelli grant; MED-EL grant; National Institutes of Health [DC01089, DC012894] FX Preliminary results of this study were presented at the Association for Research in Otolaryngology Midwinter Meeting, February 2013. This work was supported by a Fondation Bertarelli grant (D.J.L and S.L), a MED-EL grant (D.J.L), and a National Institutes of Health Grants DC01089 (M.C.B.) and DC012894 (D.P.). NR 58 TC 5 Z9 6 U1 3 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD MAR 2 PY 2015 VL 1599 BP 44 EP 56 DI 10.1016/j.brainres.2014.11.044 PG 13 WC Neurosciences SC Neurosciences & Neurology GA CD7CH UT WOS:000351247900005 PM 25481416 ER PT J AU Shen, Q Huang, SL Duong, TQ AF Shen, Qiang Huang, Shiliang Duong, Timothy Q. TI Ultra-high spatial resolution basal and evoked cerebral blood flow MRI of the rat brain SO BRAIN RESEARCH LA English DT Article DE High resolution imaging; Columnar resolution; Layer specificity; Arterial spin labeling ID FUNCTIONAL MRI; OXYGEN-CONSUMPTION; QUANTITATIVE PERFUSION; SOMATOSENSORY CORTEX; BOLD RESPONSES; STROKE MODEL; CMRO2 FMRI; SPIN-ECHO; CBF; DIFFUSION AB Cerebral blood flow (CBF) is tightly coupled to metabolism and neural activity under normal physiological conditions, and is often perturbed in disease states. The goals of this study were to implement a high-resolution (up to 50 x 38 mu m(2)) CBF MRI protocol of the rat brain, create a digital CBF atlas, report CBF values for 30+ brain structures based on the atlas, and explore applications of high-resolution CBF fMRI of forepaw stimulation. Excellent blood-flow contrasts were observed among different cortical and subcortical structures. CBF MRI showed column-like alternating bright and dark bands in the neocortices, reflecting the layout of descending arterioles and ascending venules, respectively. CBF MRI also showed lamina-like alternating bright and dark layers across the cortical thicknesses, consistent with the underlying vascular density. CBF profiles across the cortical thickness showed two peaks in layers IV and VI and a shallow trough in layer V. Whole-brain CBF was about 0.89 ml/g/min, with the highest CBF values found amongst the neocortical structures (1 ml/g/min, range: 0.89-1.16 ml/g/min) and the lowest CBF values in the corpus callosum (0.32 ml/g/min), yielding a gray:white matter CBF ratio of 3.1. CBF fMRI responses peaked across layers IV V, whereas the BOLD fMRI responses showed a peak in the superficial layers High-resolution basal CBF MRI, evoked CBF fMRI, and CBF brain atlas can be used to study neurological disorders (such as ischemic stroke). (C) 2014 Elsevier B.V. All rights reserved. C1 [Shen, Qiang; Huang, Shiliang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Shen, Qiang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Shen, Qiang/B-8784-2008 OI Shen, Qiang/0000-0002-4287-3403 FU NIH [R01NS45879]; NIH/CTSA Pilot Grant [UL1TR001120]; American Heart Association [EIA0940104N, BGIA9300047] FX This work was supported in part by NIH (R01NS45879), a NIH/CTSA Pilot Grant (via UL1TR001120), and American Heart Association (EIA0940104N, BGIA9300047). NR 50 TC 2 Z9 2 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD MAR 2 PY 2015 VL 1599 BP 126 EP 136 DI 10.1016/j.brainres.2014.12.049 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CD7CH UT WOS:000351247900012 PM 25557404 ER PT J AU Boros, E Caravan, P AF Boros, Eszter Caravan, Peter TI Probing the Structure-Relaxivity Relationship of Bis-hydrated Gd(DOTAla) Derivatives SO INORGANIC CHEMISTRY LA English DT Article ID MRI CONTRAST AGENTS; FAST WATER EXCHANGE; ACID GD-COMPLEX; LANTHANIDE(III) COMPLEXES; GADOLINIUM(III) COMPLEXES; EUROPIUM COMPLEXES; ALBUMIN-BINDING; O-17 NMR; LIGAND; LUMINESCENCE AB Two structural isomers of the heptadentate chelator DO3Ala were synthesized, with carboxymethyl groups at either the 1,4- or 1,7-positions of the cyclen macrocycle. To interrogate the relaxivity under different rotatational dynamics regimes, the pendant primary amine was coupled to ibuprofen to enable binding to serum albumin. These chelators 6a and 6b form bis(aqua) ternary complexes with Gd(III) or Tb(III) as estimated from relaxivity measurements or luminescence lifetime measurements in water. The relaxivity of [Gd(6a)(H2O)(2)] and [Gd(6b)(H2O)(2)] was measured in the presence and absence of coordinating anions prevalent in vivo such as phosphate, lactate, and bicarbonate and compared with data attained for the q = 2 complex [Gd(DO(3)A)(H2O)(2)]. We found that relaxivity was reduced through formation of ternary complexes with lactate and bicarbonate, albeit to a lesser degree then the relaxivity of Gd(DO(3)A). In the presence of 100-fold excess phosphate, relaxivity was slightly increased and typical for q = 2 complexes of this size (8.3 mM(-1) s1 and 9.5 mM(-1) s(-1), respectively, at 37 degrees C, 60 MHz). Relaxivity for the complexes in the presence of HSA corresponded well to relaxivity obtained for complexes with reduced access for inner-sphere water (13.5 and 12.7 mM(-1) s(-1) at 37 degrees C, 60 MHz). Mean water residency time at 37 degrees C was determined using temperature-dependent O-17-T2 measurements at 11.7 T and calculated to be (310)(tau M) = 23 +/- 1 ns for both structural isomers. Kinetic inertness under forcing conditions (pH 3, competing DTPA ligand) was found to be comparable to [Gd(DO(3)A)(H2O)]. Overall, we found that the replacement of one of the acetate arms of DO(3)A with an amino-propionate arm does not significantly alter the relaxometric and kinetic inertness properties of the corresponding Gd complexes; however, it does provide access to easily functionalizable q = 2 derivatives. C1 [Boros, Eszter; Caravan, Peter] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Med Sch, Charlestown, MA 02129 USA. RP Caravan, P (reprint author), Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Med Sch, 149 Thirteenth St,Suite 2301, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu FU National Institute for Biomedical Imaging and Bioengineering (NIBIB) [R01EB009062]; National Center for Research Resources [S10OD010650, S10RR023385, P41RR14075]; Swiss National Science Foundation FX P.C. acknowledges the National Institute for Biomedical Imaging and Bioengineering for funding for this project (NIBIB, Award No. R01EB009062), and the National Center for Research Resources for instrumentation grants (Nos. S10OD010650, S10RR023385, P41RR14075). E.B. thanks the Swiss National Science Foundation (Advanced Postdoc Mobility Fellowship) for support. NR 45 TC 1 Z9 1 U1 2 U2 30 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0020-1669 EI 1520-510X J9 INORG CHEM JI Inorg. Chem. PD MAR 2 PY 2015 VL 54 IS 5 BP 2403 EP 2410 DI 10.1021/ic503035f PG 8 WC Chemistry, Inorganic & Nuclear SC Chemistry GA CC5IF UT WOS:000350391600039 PM 25693053 ER PT J AU Flores, EN Duggan, A Madathany, T Hogan, AK Marquez, FG Kumar, G Seal, RP Edwards, RH Liberman, MC Garcia-Anoveros, J AF Flores, Emma N. Duggan, Anne Madathany, Thomas Hogan, Ann K. Marquez, Freddie G. Kumar, Gagan Seal, Rebecca P. Edwards, Robert H. Liberman, M. Charles Garcia-Anoveros, Jaime TI A Non-canonical Pathway from Cochlea to Brain Signals Tissue-Damaging Noise SO CURRENT BIOLOGY LA English DT Article ID OUTER HAIR-CELLS; VESICULAR GLUTAMATE TRANSPORTER-3; AUDITORY-NERVE FIBERS; SPIRAL GANGLION-CELLS; GUINEA-PIG; CENTRAL TRAJECTORIES; RECIPROCAL SYNAPSES; AFFERENT-FIBERS; MOUSE; MICE AB Intense noise damages the cochlear organ of Corti, particularly the outer hair cells (OHCs) [1]; however, this epithelium is not innervated by nociceptors of somatosensory ganglia, which detect damage elsewhere in the body. The only sensory neurons innervating the organ of Corti originate from the spiral ganglion, roughly 95% of which innervate exclusively inner hair cells (IHCs) [2-4]. Upon sound stimulation, IHCs release glutamate to activate AMPA-type receptors on these myelinated type-I neurons, which carry the neuronal signals to the cochlear nucleus. The remaining spiral ganglion cells (type IIs) are unmyelinated and contact OHCs [2-4]. Their function is unknown. Using immunoreactivity to cFos, we documented neuronal activation in the brainstem of Vglut3(-/-) mice, in which the canonical auditory pathway (activation of type-I afferents by glutamate released from inner hair cells) is silenced [5, 6]. In these deaf mice, we found responses to noxious noise, which damages hair cells, but not to innocuous noise, in neurons of the cochlear nucleus, but not in the vestibular or trigeminal nuclei. This response originates in the cochlea and not in other areas also stimulated by intense noise (middle ear and vestibule) as it was absent in CD1 mice with selective cochlear degeneration but normal vestibular and somatosensory function. These data imply the existence of an alternative neuronal pathway from cochlea to brainstem that is activated by tissue-damaging noise and does not require glutamate release from IHCs. This detection of noise-induced tissue damage, possibly by type-II cochlear afferents, represents a novel form of sensation that we term auditory nociception. C1 [Flores, Emma N.; Duggan, Anne; Madathany, Thomas; Hogan, Ann K.; Marquez, Freddie G.; Kumar, Gagan; Garcia-Anoveros, Jaime] Northwestern Univ, Dept Anesthesiol, Feinberg Sch Med, Chicago, IL 60611 USA. [Garcia-Anoveros, Jaime] Northwestern Univ, Dept Neurol, Feinberg Sch Med, Chicago, IL 60611 USA. [Garcia-Anoveros, Jaime] Northwestern Univ, Dept Physiol, Feinberg Sch Med, Chicago, IL 60611 USA. [Garcia-Anoveros, Jaime] Northwestern Univ, Hugh Knowles Ctr Clin & Basic Sci Hearing & Its D, Feinberg Sch Med, Chicago, IL 60611 USA. [Seal, Rebecca P.; Edwards, Robert H.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA. [Seal, Rebecca P.; Edwards, Robert H.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA. [Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Liberman, M. Charles] Harvard Univ, Dept Otol & Laryngol, Sch Med, Boston, MA 02114 USA. RP Garcia-Anoveros, J (reprint author), Northwestern Univ, Dept Anesthesiol, Feinberg Sch Med, Chicago, IL 60611 USA. EM anoveros@northwestern.edu FU Office of Naval Research [F31DC012013, R01DC00188, R01NS044363, R21 DC006089, N00014-14-1-0709] FX We thank Claus-Peter Richter for auditory testing facilities and supervision and Jody Ciolino (Robert H. Lurie Biostatistics Facility) for statistics. This work was funded by F31DC012013 (E.N.F.), R01DC00188 (M.C.L.), and R01NS044363, R21 DC006089, and N00014-14-1-0709 from the Office of Naval Research (J.G.-A.). NR 40 TC 14 Z9 14 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD MAR 2 PY 2015 VL 25 IS 5 BP 606 EP 612 DI 10.1016/j.cub.2015.01.009 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CC9RP UT WOS:000350708800023 PM 25639244 ER PT J AU Choi, M Lee, WM Yun, SH AF Choi, Myunghwan Lee, Woei Ming Yun, Seok Hyun TI Intravital Microscopic Interrogation of Peripheral Taste Sensation SO SCIENTIFIC REPORTS LA English DT Article ID SWEET TASTE; RAT TONGUE; RECEPTORS; CELLS; BUDS; BRAIN; MICE AB Intravital microscopy is a powerful tool in neuroscience but has not been adapted to the taste sensory organ due to anatomical constraint. Here we developed an imaging window to facilitate microscopic access to the murine tongue in vivo. Real-time two-photon microscopy allowed the visualization of three-dimensional microanatomy of the intact tongue mucosa and functional activity of taste cells in response to topically administered tastants in live mice. Video microscopy also showed the calcium activity of taste cells elicited by small-sized tastants in the blood circulation. Molecular kinetic analysis suggested that intravascular taste sensation takes place at the microvilli on the apical side of taste cells after diffusion of the molecules through the pericellular capillaries and tight junctions in the taste bud. Our results demonstrate the capabilities and utilities of the new tool for taste research in vivo. C1 [Choi, Myunghwan; Lee, Woei Ming; Yun, Seok Hyun] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02139 USA. [Choi, Myunghwan; Lee, Woei Ming; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02139 USA. [Choi, Myunghwan] Sungkyunkwan Univ, Global Biomed Engn, Suwon, South Korea. [Lee, Woei Ming] Australian Natl Univ, Res Sch Engn, Canberra, ACT 0200, Australia. RP Yun, SH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 65 Landsdowne St,UP-5, Cambridge, MA 02139 USA. EM syun@mgh.harvard.edu OI Lee, W M Steve/0000-0002-3912-6095; Choi, Myunghwan/0000-0002-4235-7003 FU U.S. National Institutes of Health [P41EB015903, U54CA143837]; National Research Foundation of Korea [NRF-2013R1A6A3A03060958] FX We thank K.B. Lee, H. Koo, and S.J.J. Kwok in the Wellman Center for Photomedicine for helpful discussions and J. M. Bekker in Australian National University for comments. This work was in part funded by the U.S. National Institutes of Health (P41EB015903, U54CA143837) and a Postdoctoral Fellowship from the National Research Foundation of Korea (NRF-2013R1A6A3A03060958). NR 33 TC 1 Z9 1 U1 2 U2 7 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 MAR 2 PY 2015 VL 5 AR 8661 DI 10.1038/srep08661 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CC4DF UT WOS:000350300300006 PM 25726964 ER PT J AU Kales, HC Gitlin, LN Lyketsos, CG AF Kales, Helen C. Gitlin, Laura N. Lyketsos, Constantine G. TI Assessment and management of behavioral and psychological symptoms of dementia SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Review ID ALZHEIMERS-DISEASE PATIENTS; ATYPICAL ANTIPSYCHOTIC MEDICATIONS; SEROTONIN REUPTAKE INHIBITORS; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIALS; HOME-BASED INTERVENTION; TO-MODERATE DEMENTIA; NEUROPSYCHIATRIC-SYMPTOMS; DOUBLE-BLIND; NURSING-HOME AB Behavioral and psychological symptoms of dementia include agitation, depression, apathy, repetitive questioning, psychosis, aggression, sleep problems, wandering, and a variety of inappropriate behaviors. One or more of these symptoms will affect nearly all people with dementia over the course of their illness. These symptoms are among the most complex, stressful, and costly aspects of care, and they lead to a myriad of poor patient health outcomes, healthcare problems, and income loss for family care givers. The causes include neurobiologically related disease factors; unmet needs; care giver factors; environmental triggers; and interactions of individual, care giver, and environmental factors. The complexity of these symptoms means that there is no "one size fits all solution," and approaches tailored to the patient and the care giver are needed. Non-pharmacologic approaches should be used first line, although several exceptions are discussed. Non-pharmacologic approaches with the strongest evidence base involve family care giver interventions. Regarding pharmacologic treatments, antipsychotics have the strongest evidence base, although the risk to benefit ratio is a concern. An approach to integrating non-pharmacologic and pharmacologic treatments is described. Finally, the paradigm shift needed to fully institute tailored treatments for people and families dealing with these symptoms in the community is discussed. C1 [Kales, Helen C.] Univ Michigan, Dept Psychiat, Sect Geriatr Psychiat, Ann Arbor, MI 48109 USA. [Kales, Helen C.] US Dept Vet Affairs, Ctr Clin Management Res, Ann Arbor, MI USA. [Kales, Helen C.] VA Ann Arbor Healthcare Syst, Geriatr Res Educ & Clin Ctr, Ann Arbor, MI USA. [Gitlin, Laura N.] Johns Hopkins Univ, Sch Nursing, Dept Community Publ Hlth, Baltimore, MD USA. [Gitlin, Laura N.] Johns Hopkins Univ, Sch Med, Div Geriatr & Gerontol, Baltimore, MD USA. [Gitlin, Laura N.] Johns Hopkins Univ, Ctr Innovat Care Aging, Baltimore, MD USA. [Lyketsos, Constantine G.] Johns Hopkins Bayview, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Lyketsos, Constantine G.] Johns Hopkins Univ, Baltimore, MD USA. RP Kales, HC (reprint author), Univ Michigan, Dept Psychiat, Sect Geriatr Psychiat, Ann Arbor, MI 48109 USA. EM kales@umich.edu FU Johns Hopkins Alzheimer's Disease Research Center [P50AG005146]; [R01NR014200] FX HCK and LNG were supported in part by R01NR014200. CGL was supported in part by the Johns Hopkins Alzheimer's Disease Research Center (P50AG005146). NR 172 TC 37 Z9 38 U1 14 U2 57 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 MAR 2 PY 2015 VL 350 AR h369 DI 10.1136/bmj.h369 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA CC4BV UT WOS:000350296600007 PM 25731881 ER PT J AU Hoguet, A Parrish, RK AF Hoguet, Ambika Parrish, Richard K., II TI Unexpected Hypotony After Glaucoma Drainage Implant Surgery Associated With Anti-Vascular Endothelial Growth Factor Treatment SO JAMA OPHTHALMOLOGY LA English DT Letter ID BEVACIZUMAB; SUBCONJUNCTIVAL; TRABECULECTOMY C1 [Hoguet, Ambika] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Parrish, Richard K., II] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USA. RP Hoguet, A (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM ambika.sud@gmail.com FU NEI NIH HHS [P0EY01480] 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 MAR PY 2015 VL 133 IS 3 BP 349 EP 350 DI 10.1001/jamaophthalmol.2014.5058 PG 2 WC Ophthalmology SC Ophthalmology GA CD6UE UT WOS:000351224200020 PM 25474585 ER PT J AU Nogiec, C Burkart, A Dreyfuss, JM Lerin, C Kasif, S Patti, ME AF Nogiec, Christopher Burkart, Alison Dreyfuss, Jonathan M. Lerin, Carles Kasif, Simon Patti, Mary-Elizabeth TI Metabolic modeling of muscle metabolism identifies key reactions linked to insulin resistance phenotypes SO MOLECULAR METABOLISM LA English DT Article DE Muscle insulin resistance; Muscle metabolism; Flux balance analysis; Computational modeling ID HUMAN SKELETAL-MUSCLE; PYRUVATE-DEHYDROGENASE; DIABETES-MELLITUS; GLOBAL RECONSTRUCTION; HEART-MITOCHONDRIA; ATP SYNTHESIS; OXIDATION; NETWORK; GLUCOSE; EXERCISE AB Objective: Dysregulated muscle metabolism is a cardinal feature of human insulin resistance (IR) and associated diseases, including type 2 diabetes (T2D). However, specific reactions contributing to abnormal energetics and metabolic inflexibility in IR are unknown. Methods: We utilize flux balance computational modeling to develop the first systems-level analysis of IR metabolism in fasted and fed states, and varying nutrient conditions. We systematically perturb the metabolic network to identify reactions that reproduce key features of IR-linked metabolism. Results: While reduced glucose uptake is a major hallmark of IR, model-based reductions in either extracellular glucose availability or uptake do not alter metabolic flexibility, and thus are not sufficient to fully recapitulate IR-linked metabolism. Moreover, experimentally-reduced flux through single reactions does not reproduce key features of IR-linked metabolism. However, dual knockdowns of pyruvate dehydrogenase (PDH), in combination with reduced lipid uptake or lipid/amino acid oxidation (ETFDH), does reduce ATP synthesis, TCA cycle flux, and metabolic flexibility. Experimental validation demonstrates robust impact of dual knockdowns in PDH/ETFDH on cellular energetics and TCA cycle flux in cultured myocytes. Parallel analysis of transcriptomic and metabolomics data in humans with IR and T2D demonstrates downregulation of PDH subunits and upregulation of its inhibitory kinase PDK4, both of which would be predicted to decrease PDH flux, concordant with the model. Conclusions: Our results indicate that complex interactions between multiple biochemical reactions contribute to metabolic perturbations observed in human IR, and that the PDH complex plays a key role in these metabolic phenotypes. (C) 2014 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). C1 [Nogiec, Christopher] Boston Univ, Grad Program Bioinformat, Boston, MA 02215 USA. [Burkart, Alison; Dreyfuss, Jonathan M.; Lerin, Carles; Kasif, Simon; Patti, Mary-Elizabeth] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Burkart, Alison; Patti, Mary-Elizabeth] Harvard Univ, Sch Med, Boston, MA USA. [Dreyfuss, Jonathan M.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Kasif, Simon] Boston Univ, Biomed Engn, Boston, MA 02215 USA. [Kasif, Simon] Harvard Mit Div Hlth Sci & Technol, Childrens Hosp Informat Program, Boston, MA USA. RP Patti, ME (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM Nogiec@bu.edu; Alison.burkart@joslin.harvard.edu; clerin@fsjd.edu; Kasif@bu.edu; mary.elizabeth.patti@joslin.harvard.edu OI Dreyfuss, Jonathan/0000-0001-7242-3991 FU NIDDK NIH HHS [P30 DK036836, T32 DK007260]; NLM NIH HHS [U54 LM008748] NR 71 TC 7 Z9 8 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2212-8778 J9 MOL METAB JI Mol. Metab. PD MAR PY 2015 VL 4 IS 3 BP 151 EP 163 DI 10.1016/j.molmet.2014.12.012 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CZ9RH UT WOS:000367434200001 PM 25737951 ER PT J AU Hobbs, GS Perales, MA AF Hobbs, Gabriela Soriano Perales, Miguel-Angel TI Effects of T-Cell Depletion on Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in AML Patients SO JOURNAL OF CLINICAL MEDICINE LA English DT Review DE AML; CD34+ selection; T-cell depletion; graft-versus-host disease; hematopoietic stem cell transplantation ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; ACUTE MYELOID-LEUKEMIA; 1ST COMPLETE REMISSION; MONOCLONAL-ANTIBODY OKT3; RED-BLOOD-CELLS; UNRELATED-DONOR; HEMATOLOGIC MALIGNANCIES; ANTITHYMOCYTE GLOBULIN AB Graft versus host disease (GVHD) remains one of the leading causes of morbidity and mortality associated with conventional allogeneic hematopoietic stem cell transplantation (HCT). The use of T-cell depletion significantly reduces this complication. Recent prospective and retrospective data suggest that, in patients with AML in first complete remission, CD34+ selected grafts afford overall and relapse-free survival comparable to those observed in recipients of conventional grafts, while significantly decreasing GVHD. In addition, CD34+ selected grafts allow older patients, and those with medical comorbidities or with only HLA-mismatched donors to successfully undergo transplantation. Prospective data are needed to further define which groups of patients with AML are most likely to benefit from CD34+ selected grafts. Here we review the history of T-cell depletion in AML, and techniques used. We then summarize the contemporary literature using CD34+ selection in recipients of matched or partially mismatched donors (7/8 or 8/8 HLA-matched), and provide a summary of the risks and benefits of using T-cell depletion. C1 [Hobbs, Gabriela Soriano] Massachusetts Gen Hosp, Adult Leukemia Serv, Boston, MA 02114 USA. [Hobbs, Gabriela Soriano] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Perales, Miguel-Angel] Mem Sloan Kettering Canc Ctr, Adult Bone Marrow Transplantat Serv, New York, NY 10065 USA. [Perales, Miguel-Angel] Weill Cornell Med Coll, New York, NY 10065 USA. RP Perales, MA (reprint author), Mem Sloan Kettering Canc Ctr, Adult Bone Marrow Transplantat Serv, New York, NY 10065 USA. EM ghobbs@partners.org; peralesm@mskcc.org OI Hobbs, Gabriela/0000-0002-0199-9333 FU NCI NIH HHS [P01 CA023766] NR 79 TC 1 Z9 1 U1 0 U2 0 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2077-0383 J9 J CLIN MED JI J. Clin. Med. PD MAR PY 2015 VL 4 IS 3 BP 488 EP 503 DI 10.3390/jcm4030488 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA CT9KT UT WOS:000363136600009 PM 26239251 ER PT J AU Lee, CT Chuang, SK Stoupel, J AF Lee, Chun-Teh Chuang, Sung-Kiang Stoupel, Janet TI Survival Analysis and Other Clinical Outcomes of Immediate Implant Placement in Sites with Periapical Lesions: Systematic Review SO INTERNATIONAL JOURNAL OF ORAL & MAXILLOFACIAL IMPLANTS LA English DT Article DE dental implants; evidence-based dentistry; oral pathology ID OF-THE-LITERATURE; DENTAL IMPLANTS; INFECTED SITES; EXTRACTION SOCKETS; RETROSPECTIVE ANALYSIS; ENDODONTIC SURGERY; CONSENSUS CONFERENCE; BONE REGENERATION; FOLLOW-UP; TEETH AB Purpose: Immediate implantation has become one of the therapeutic options for replacement of a hopeless tooth. In the case of a tooth with a periapical lesion, this approach remains controversial. The aims of this article were to systematically review the evidence on immediate implants in sites with periapical lesions with reference to: (1) survival rates, (2) changes in crestal bone levels and marginal tissues, (3) complication rates, and (4) comparison of clinical outcomes with other implant treatments. Materials and Methods: An electronic search was conducted in MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE for articles published between January 1990 and August 2013. Publications were screened, and data extraction and quality assessment were performed. Implant survival rates were calculated using predicted Ka survival analysis. Crestal bone level changes, soft tissue outcomes, complications, and procedure characteristics were analyzed descriptively. Results: Initially, 301 articles were identified. Three prospective controlled trials of immediate implant placement in sites with periapical lesions with a follow-up period of at least 1 year were selected for the survival analysis. The predicted cumulative 5-year survival rate of immediate implants in sites with periapical lesions was 96.23%. Bone and gingival level changes were comparable to those of implants placed in sites without periapical pathology. The complication rates, reported in only one study, were 15.4% (2/13) in sites with periapical lesions and 6.7% (1/15) in healthy sites. Conclusion: Limited evidence suggests that immediate implant placement in sites with periapical lesions leads to clinical outcomes comparable to those of immediate implants in healthy sites. Additional prospective controlled trials with large sample sizes and long-term follow-up are needed to further investigate these results. C1 [Lee, Chun-Teh] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Div Periodontol, Boston, MA 02115 USA. [Chuang, Sung-Kiang] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Chuang, Sung-Kiang] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Stoupel, Janet] Columbia Univ, Coll Dent Med, Div Periodont, Sect Oral & Diagnost Sci, New York, NY USA. RP Lee, CT (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. EM chun-teh_lee@hsdm.harvard.edu NR 82 TC 3 Z9 3 U1 4 U2 4 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA SN 0882-2786 EI 1942-4434 J9 INT J ORAL MAX IMPL JI Int. J. Oral Maxillofac. Implants PD MAR-APR PY 2015 VL 30 IS 2 BP 268 EP 278 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CZ6XB UT WOS:000367243200003 PM 25830386 ER PT J AU Zafar, SY McNeil, RB Thomas, CM Lathan, CS Ayanian, JZ Provenzale, D AF Zafar, S. Yousuf McNeil, Rebecca B. Thomas, Catherine M. Lathan, Christopher S. Ayanian, John Z. Provenzale, Dawn TI Population-Based Assessment of Cancer Survivors' Financial Burden and Quality of Life: A Prospective Cohort Study SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID CARE OUTCOMES RESEARCH; PATIENTS EXPERIENCE; BREAST-CANCER; TOXICITY; ADULTS; COSTS; WOMEN; RISK AB Purpose: The impact of financial burden among patients with cancer has not yet been measured in a way that accounts for inter-relationships between quality of life, perceived quality of care, disease status, and sociodemographic characteristics. Patients and Methods: In a national, prospective, observational, population-and health care systems-based cohort study, patients with colorectal or lung cancer were enrolled from 2003 to 2006 within 3 months of diagnosis. For this analysis, surviving patients who were either disease free or had advanced disease were resurveyed a median 7.3 years from diagnosis. Structural equation modeling was used to investigate relationships between financial burden, quality of life, perceived quality of care, and sociodemographic characteristics. Results: Among 1,000 participants enrolled from five geographic regions, five integrated health care systems, or 15 Veterans Administration Hospitals, 89% (n = 889) were cancer free, and 11% (n = 111) had advanced cancer. Overall, 48% (n = 482) reported difficulties living on their household income, and 41% (n = 396) believed their health care to be "excellent." High financial burden was associated with lower household income (adjusted odds ratio [OR] = 0.61 per $20k per year, P < .001) and younger age (adjusted OR = 0.63 per 10 years; P < .001). High financial burden was also associated with poorer quality of life (adjusted beta = -0.06 per burden category; P < .001). Better quality of life was associated with fewer perceptions of poorer quality of care (adjusted OR = 0.85 per 0.10 EuroQol units; P < .001). Conclusion: Financial burden is prevalent among cancer survivors and is related to patients' health-related quality of life. Future studies should consider interventions to improve patient education and engagement with regard to financial burden. C1 Duke Canc Inst, Durham, NC USA. Duke Clin Res Inst, Ctr Learning Hlth Care, Durham, NC USA. [Zafar, S. Yousuf] Duke Univ, Med Ctr, Durham, NC 27705 USA. Durham Vet Affairs Med Ctr Durham, Epidemiol Ctr Durham, Cooperat Studies Program, Durham, NC USA. Med Univ S Carolina, Charleston, SC 29425 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Zafar, SY (reprint author), Duke Univ, Med Ctr, DUMC 3850,2400 Pratt St,Rm 8039, Durham, NC 27705 USA. EM yousuf.zafar@duke.edu FU NCI NIH HHS [1-KM1-CA-156687-01, KM1 CA156687, U01 CA093324, U01 CA093326, U01 CA093329, U01 CA093332, U01 CA093339, U01 CA093344, U01 CA093348] NR 33 TC 18 Z9 18 U1 3 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD MAR PY 2015 VL 11 IS 2 BP 145 EP U472 DI 10.1200/JOP.2014.001542 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CY1PA UT WOS:000366178400032 PM 25515717 ER PT J AU Margalit, DN Losi, SM Tishler, RB Schoenfeld, JD Fugazzotto, JA Stephens, J Cebulski, AL Hammerstrand, EL Ma, L Lopes, HM Haddad, RI Treister, NS Frustino, JL AF Margalit, Danielle N. Losi, Stephanie M. Tishler, Roy B. Schoenfeld, Jonathan D. Fugazzotto, Jo Ann Stephens, Josie Cebulski, Amy L. Hammerstrand, Elizabeth L. Ma, Laura Lopes, Holly M. Haddad, Robert I. Treister, Nathaniel S. Frustino, Jennifer L. TI Ensuring Head and Neck Oncology Patients Receive Recommended Pretreatment Dental Evaluations SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID CARE AB Purpose: Head and neck (H&N) cancer therapy can have a detrimental effect on oral health by increasing the risk of dry mouth, dental caries, dental infection, and osteonecrosis of the jaw. Pretreatment dental evaluations are recommended for patients with H&N cancer before radiation therapy to minimize the risk of acute and long-term adverse effects. In an earlier effort to educate patients and community dentists about the importance of pretreatment dental evaluations, we created a dental instructional guide (DIG) that outlines the necessary components of the preradiation dental evaluation. Yet our program did not have a system for documenting which patients received the DIG. The aim of this project was to create a reliable system to ensure that patients are given the DIG before radiation therapy and that such patients are readily identifiable, allowing us to confirm that their dental evaluations are complete before starting treatment. Methods: We implemented a tracking template within the H&N oncology program at the Dana-Farber Cancer Institute that documents the date, patient, and clinician who gave the DIG. We used the Model for Improvement methodology and performed plan-do-study-act (PDSA) cycles to test and monitor the results of the template implementation. Results: We showed a significant improvement in the rate of DIG documentation from a baseline of 0% (range, 0% to 0%) to a mean of 53% (range, 0% to 100%) over 3 months (P < .01). Conclusion: This intervention was the first step in creating a sustainable system for ensuring timely preradiation dental evaluation, thereby decreasing the risk of dental complications from H&N cancer therapy. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Ctr Clin Excellence, Boston, MA 02115 USA. Erie Cty Med Ctr & Labs, Ctr Oncol Care, Buffalo, NY USA. RP Margalit, DN (reprint author), Dept Radiat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM dmargalit@lroc.harvard.edu NR 6 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD MAR PY 2015 VL 11 IS 2 BP 151 EP U504 DI 10.1200/JOP.2014.000414 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CY1PA UT WOS:000366178400033 PM 25628388 ER PT J AU Kehl, KL Gray, SW Kim, B Kahn, KL Haggstrom, D Roudier, M Keating, NL AF Kehl, Kenneth L. Gray, Stacy W. Kim, Benjamin Kahn, Katherine L. Haggstrom, David Roudier, Maryse Keating, Nancy L. TI Oncologists' Experiences With Drug Shortages SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID ADVANCED COLORECTAL-CANCER; RACEMIC LEUCOVORIN; UNITED-STATES; L-ISOMER; CARE; IMPACT; LEVOLEUCOVORIN AB Purpose: There have been numerous reports of shortages of injectable drugs for cancer in the last decade. Weassessed physician experiences with drug shortages in a population-based cohort of medical oncologists caring for patients with lung or colorectal cancer. Methods: We surveyed medical oncologists caring for patients with lung or colorectal cancer in the Cancer Care Outcomes Research and Surveillance Consortium from 2012 to 2013 (participation rate, 53%). Oncologists reported experiences with shortages of leucovorin, fluorouracil, dexamethasone, cyanocobalamin, paclitaxel, cisplatin, and etoposide in the prior year and whether they had used a less-effective alternative because of a shortage. We used multivariable logistic regression to assess for associations between physician or practice characteristics and encountering shortages. Results: Among 330 respondents, 74% reported experiences with a shortage of at least one drug in our survey, and 28% reported using a less-effective alternative because of a shortage. Although physician demographic characteristics did not predict reports of drug shortages, practice characteristics did. Veterans Affairs (VA) oncologists were less likely to report experiencing any shortage than oncologists in single-specialty group practice (odds ratio [OR], 0.4; 95% CI, 0.2 to 0.9). The reported use of a less effective alternative to any drug was also less common among VA oncologists (OR, 0.3; 95% CI, 0.1 to 0.9) and oncologists affiliated with health maintenance organizations (OR, 0.4; 95% CI, 0.2 to 0.9) compared with physicians in single-specialty groups. Conclusion: Most oncologists encountered drug shortages in the year before our survey, but experiences with shortages varied with practice structure. Further research is needed to quantitatively assess the impact of drug shortages on patients and evaluate various strategies for managing them. C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. Vet Affairs VA Hlth Serv Res & Dev, Roudebush, VA USA. Indiana Univ Sch Med, Indianapolis, IN 46202 USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu FU NCI NIH HHS [K24 CA181510] NR 30 TC 5 Z9 5 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD MAR PY 2015 VL 11 IS 2 BP E154 EP E162 DI 10.1200/JOP.2014.000380 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CY1PA UT WOS:000366178400006 PM 25549653 ER PT J AU Palmer, SC Stricker, CT Panzer, SL Arvey, SA Baker, KS Casillas, J Ganz, PA McCabe, MS Nekhlyudov, L Overholser, L Partridge, AH Risendal, B Rosenstein, DL Syrjala, KL Jacobs, LA AF Palmer, Steven C. Stricker, Carrie Tompkins Panzer, SarahLena L. Arvey, Sarah A. Baker, K. Scott Casillas, Jackie Ganz, Patricia A. McCabe, Mary S. Nekhlyudov, Larissa Overholser, Linda Partridge, Ann H. Risendal, Betsy Rosenstein, Donald L. Syrjala, Karen L. Jacobs, Linda A. TI Outcomes and Satisfaction After Delivery of a Breast Cancer Survivorship Care Plan: Results of a Multicenter Trial SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID COLORECTAL-CANCER; FOLLOW-UP; PATIENT SATISFACTION; HEALTH-CARE; PREFERENCES; ADULT; INFORMATION; PERSPECTIVE; DIAGNOSIS; SERVICES AB Purpose: Survivorship care plans (SCPs) have been suggested to reduce fragmentation of care experienced by cancer survivors. Acceptance of SCPs is high, but trials in the United States are few. This pilot study used a quasiexperimental design to examine the outcomes achieved by breast cancer survivors receiving a standardized SCP visit at one of seven comprehensive cancer centers. Materials and Methods: Outcomes were assessed before and again 3 months after delivery of an SCP and included survivors' use of and satisfaction with SCPs, perceived knowledge about survivorship, and assessment of the quality and coordination of survivorship care. Results: One hundred thirty-nine survivors of breast cancer completed baseline and follow-up measures and received a standardized SCP visit. Participants most commonly used SCP materials to make decisions about exercise (64%), which tests to receive and when (62%), and dietary changes (62%). Only 21% shared the SCP with their primary care provider during that time. Satisfaction with the SCP was high, with 90% of participants reporting being at least satisfied with the SCP. Perceived knowledge about survivorship improved after SCP delivery, as did perceived care coordination and the provider's knowledge of the effects of cancer on survivors (all P < .001). Individuals closer to the time of diagnosis reported greater satisfaction with and use of SCPs. Conclusion: This study demonstrates improvements in perceived knowledge and quality of survivorship care after receipt of a comprehensive SCP. Survivors were satisfied with their SCP, and those closer to diagnosis reported greater satisfaction with and use of the materials. C1 Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. LIVESTRONG, Austin, TX USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Colorado, Ctr Canc, Denver, CO 80262 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Palmer, SC (reprint author), 3400 Civ Ctr Blvd,3 WEST, Philadelphia, PA 19104 USA. EM Stpalmer@mail.med.upenn.edu FU NCI NIH HHS [R01 CA160684] NR 45 TC 8 Z9 8 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD MAR PY 2015 VL 11 IS 2 BP E222 EP E229 DI 10.1200/JOP.2014.001404 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CY1PA UT WOS:000366178400016 PM 25784579 ER PT J AU Zerillo, JA Pham, TH Kadlubek, P Severson, JA Mackler, E Jacobson, JO Blayney, DW AF Zerillo, Jessica A. Pham, Trang H. Kadlubek, Pamela Severson, Jane Alcyne Mackler, Emily Jacobson, Joseph O. Blayney, Douglas W. TI Administration of Oral Chemotherapy: Results From Three Rounds of the Quality Oncology Practice Initiative SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; PEDIATRIC-PATIENTS; COLORECTAL-CANCER; ADHERENCE; CARE; SAFETY; AGENTS AB Purpose: Although use of oral chemotherapy is becoming more prevalent, little is known about the quality of care that patients receive when these agents are prescribed. Moreover, few practice-level systems are in place to ensure safe management of oral chemotherapy in the vulnerable population of patients with cancer. Methods: We analyzed results from 155 practices that were voluntarily participating in the American Society of Clinical Oncology Quality Oncology Practice Initiative (QOPI) program on 17 test measures of oral chemotherapy administration and management in at least one of three collection periods: spring or fall of 2012, or spring of 2013. The 17 test measures cover three domains: treatment plan documentation, patient education, and adherence/toxicity monitoring. We defined composite scores for each of the three domains. We analyzed the composite scores by secular trend and tested the difference in composite scores for the three domains. Additionally, we tested change in scores over time among practices that participated at least twice. Results: The majority of data was provided by QOPI-certified practices. Overall, mean practice composite scores ranged from 66% to 68% for treatment plan documentation, 51% to 57% for patient education, and 75% to 81% for adherence/toxicity monitoring. Composite scores for practices that participated more than once did not improve significantly. Conclusion: The collection of oral chemotherapy test measure data is feasible. Composite scores for treatment plan documentation and patient education were not only lower, but had greater variability compared with adherence/toxicity monitoring. Improvement opportunities exist for patients who are prescribed oral chemotherapy. C1 [Zerillo, Jessica A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Amer Soc Clin Oncol, Alexandria, VA USA. Michigan Oncol Qual Consortium, Ann Arbor, MI USA. Stanford Canc Inst, Stanford, CA USA. RP Zerillo, JA (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,Shapiro 913, Boston, MA 02215 USA. EM jzerillo@bidmc.harvard.edu NR 37 TC 2 Z9 2 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD MAR PY 2015 VL 11 IS 2 BP E255 EP E262 DI 10.1200/JOP.2014.001842 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CY1PA UT WOS:000366178400020 PM 25784581 ER PT J AU Felker, GM Butler, J Collins, SP Cotter, G Davison, BA Ezekowitz, JA Filippatos, G Levy, PD Metra, M Ponikowski, P Soergel, DG Teerlink, JR Violin, JD Voors, AA Pang, PS AF Felker, G. Michael Butler, Javed Collins, Sean P. Cotter, Gad Davison, Beth A. Ezekowitz, Justin A. Filippatos, Gerasimos Levy, Phillip D. Metra, Marco Ponikowski, Piotr Soergel, David G. Teerlink, John R. Violin, Jonathan D. Voors, Adriaan A. Pang, Peter S. TI Heart Failure Therapeutics on the Basis of a Biased Ligand of the Angiotensin-2 Type 1 Receptor Rationale and Design of the BLAST-AHF Study (Biased Ligand of the Angiotensin Receptor Study in Acute Heart Failure) SO JACC-HEART FAILURE LA English DT Article DE BLAST-AHF; NT-proBNP; TRV027 ID LEFT-VENTRICULAR DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; MULTIPLE END-POINTS; CLINICAL-TRIALS; INTRAVENOUS ENALAPRILAT; CARDIAC MYOCYTES; BETA-ARRESTINS; I RECEPTOR; PHASE-II; ASSOCIATION AB The BLAST-AHF (Biased Ligand of the Angiotensin Receptor Study in Acute Heart Failure) study is designed to test the efficacy and safety of TRV027, a novel biased ligand of the angiotensin-2 type 1 receptor, in patients with acute heart failure (AHF). AHF remains a major public health problem, and no currently-available therapies have been shown to favorably affect outcomes. TRV027 is a novel biased ligand of the angiotensin-2 type 1 receptor that antagonizes angiotensin-stimulated G-protein activation while stimulating beta-arrestin. In animal models, these effects reduce afterload while increasing cardiac performance and maintaining stroke volume. In initial human studies, TRV027 appears to be hemodynamically active primarily in patients with activation of the renin-angiotensin-aldosterone system, a potentially attractive profile for an AHF therapeutic. BLAST-AHF is an international prospective, randomized, phase IIb, dose-ranging study that will randomize up to 500 AHF patients with systolic blood pressure >= 120 mm Hg and <= 200 mm Hg within 24 h of initial presentation to 1 of 3 doses of intravenous TRV027 (1, 5, or 25 mg/h) or matching placebo (1: 1: 1: 1) for at least 48 h and up to 96 h. The primary endpoint is a composite of 5 clinical endpoints (dyspnea, worsening heart failure, length of hospital stay, 30-day rehospitalization, and 30-day mortality) combined using an average z-score. Secondary endpoints will include the assessment of dyspnea and change in amino-terminal pro-B-type natriuretic peptide. The BLAST-AHF study will assess the efficacy and safety of a novel biased ligand of the angiotensin-2 type 1 receptor in AHF. (C) 2015 by the American College of Cardiology Foundation. C1 [Felker, G. Michael] Duke Univ, Sch Med, Div Cardiol, Durham, NC USA. [Butler, Javed] SUNY Stony Brook, Div Cardiol, Stony Brook, NY 11794 USA. [Collins, Sean P.] Vanderbilt Univ, Dept Emergency Med, Nashville, TN 37235 USA. [Cotter, Gad; Davison, Beth A.] Momentum Res Inc, Durham, NC USA. [Ezekowitz, Justin A.] Univ Alberta, Canadian VIGOUR Ctr, Edmonton, AB, Canada. [Filippatos, Gerasimos] Athens Univ Hosp Attikon, Dept Cardiol, Athens, Greece. [Levy, Phillip D.] Wayne State Sch Med, Dept Emergency Med, Detroit, MI USA. [Levy, Phillip D.] Wayne State Sch Med, Cardiovasc Res Inst, Detroit, MI USA. [Metra, Marco] Univ Brescia, Dept Med & Surg Specialties, Cardiol, Radiol Sci & Publ Hlth, Brescia, Italy. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Dept Cardiol, Wroclaw, Poland. [Soergel, David G.; Violin, Jonathan D.] Trevena Inc, King Of Prussia, PA USA. [Teerlink, John R.] San Francisco VA Med Ctr, Cardiol Sect, San Francisco, CA USA. [Teerlink, John R.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Pang, Peter S.] Indiana Univ Sch Med, Dept Emergency Med, Indianapolis, IN 46202 USA. RP Felker, GM (reprint author), Duke Clin Res Inst, 2400 Pratt St,Room 0311 Terrace Level, Durham, NC 27710 USA. EM Michael.felker@duke.edu RI Ponikowski, Piotr/O-6454-2015 OI Ponikowski, Piotr/0000-0002-3391-7064 FU Trevena, Inc.; National Heart, Lung, and Blood Institute; Novartis; Roche Diagnostics; Otsuka; Amgen; National Institutes of Health (NIH); European Union; Health Resources Service Administration; NIH/National Heart, Lung, and Blood Institute; Cardiorentis; Abbott Point-of-Care; Medicines Company; Astellas; Intersection Medical; Radiometer; Medtronic; Trevena; Bayer; Cardio3Bioscience; Cytokinetics; Department of Veterans Affairs; Duke Clinical Research Institute; Janssen; Mast Therapeutics; Sorbent; St. Jude Medical FX The BLAST-AHF study is funded by Trevena, Inc. Dr. Felker has received grant support from the National Heart, Lung, and Blood Institute, Novartis, Roche Diagnostics, Otsuka, and Amgen; and has served as a consultant to Trevena, Amgen, Novartis, Celladon, Sorbent, Bristol-Myers Squibb, Singulex, St. Jude Medical, and Medtronic. Dr. Butler has received research support from the National Institutes of Health (NIH), European Union, and Health Resources Service Administration; and is a consultant to Amgen, Bayer, BG Medicine, Cardiocell, Celladon, GE Healthcare, Medtronic, Novartis, Ono Pharma, Otsuka, Takeda, Trevena, and Zensun. Dr. Collins has received research support from the NIH/National Heart, Lung, and Blood Institute, Cardiorentis, Abbott Point-of-Care, Novartis, The Medicines Company, Astellas, Intersection Medical, Radiometer, and Medtronic; and has served as a consultant to Trevena, Novartis, Cardiorentis, Otsuka, Radiometer, The Medicines Company, Medtronic, Intersection Medical, Cardioxyl, and Abbott Point-of-Care. Drs. Cotter and Davison are employees of Momentum Research, Inc., which has received compensation for coordinating research activities or participated in the design of research programs for Merck, Corthera Inc., Novartis Inc., Nile Therapeutics Inc., Amgen/Cytokinetics Inc., Travena Inc., Cardio3 Inc., Sorbent Inc., Chan Rx Inc.; and has received grants from not-for-profit nongovernmental organizations and the NIH. Dr. Davison has received honoraria from Novartis. Dr. Ezekowitz is codirector of the Canadian VIGOUR Centre, which is involved in site-management for the BLAST-AHF study. Dr. Filippatos has served on the executive committee of acute heart failure studies sponsored by Trevena, Novartis, Bayer, and Cardiorentis. Dr. Levy has served as a consultant for Trevena, Novartis, and Cardiorentis. Dr. Metra has served as a consultant for Bayer, Novartis, Servier, and Trevena. Drs. Ponikowski and Voors have served as a consultant for Trevena. Drs. Soergel and Violin are employees of Trevena. Dr. Teerlink has received research grants and/or consultant fees from Amgen, Cardio3Bioscience, Cytokinetics, Department of Veterans Affairs, Duke Clinical Research Institute, Janssen, Medtronic, Mast Therapeutics, Novartis, Sorbent, St. Jude Medical, and Trevena. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 39 TC 27 Z9 27 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1779 EI 2213-1787 J9 JACC-HEART FAIL JI JACC-Heart Fail. PD MAR PY 2015 VL 3 IS 3 BP 193 EP 201 DI 10.1016/j.jchf.2014.09.008 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX4EC UT WOS:000365650600001 PM 25650371 ER PT J AU Cerda, R Perez, F Domingues, RMSM Luz, PM Grinsztejn, B Veloso, VG Caffe, S Francke, JA Freedberg, KA Ciaranello, AL AF Cerda, Rodrigo Perez, Freddy Domingues, Rosa Maria S. M. Luz, Paula M. Grinsztejn, Beatriz Veloso, Valdilea G. Caffe, Sonja Francke, Jordan A. Freedberg, Kenneth A. Ciaranello, Andrea L. TI Prenatal Transmission of Syphilis and Human Immunodeficiency Virus in Brazil: Achieving Regional Targets for Elimination SO OPEN FORUM INFECTIOUS DISEASES LA English DT Article DE congenital syphilis; disease elimination; human immunodeficiency virus; infectious disease transmission; mathematical models; vertical transmission ID MOTHER-TO-CHILD; HIV TRANSMISSION; CONGENITAL-SYPHILIS; ANTIRETROVIRAL THERAPY; COST-EFFECTIVENESS; RANDOMIZED-TRIAL; PREGNANT-WOMEN; SOUTH-AFRICA; SAO-PAULO; PREVENTION AB Background. The Pan-American Health Organization has called for reducing (1) human immunodeficiency virus (HIV) mother-to-child transmission (MTCT) to <= 0.30 infections/1000 live births (LB), (2) HIV MTCT risk to <= 2.0%, and (3) congenital syphilis (CS) incidence to <= 0.50/1000 LB in the Americas by 2015. Methods. Using published Brazilian data in amathematical model, we simulated a cohort of pregnant women from antenatal care (ANC) through birth. We investigated 2 scenarios: "current access" (89.1% receive one ANC syphilis test and 41.1% receive 2; 81.7% receive one ANC HIV test and 18.9% receive birth testing; if diagnosed, 81.0% are treated for syphilis and 87.5% are treated for HIV) and "ideal access" (95% of women undergo 2 HIV and syphilis screenings; 95% receive appropriate treatment). We conducted univariate and multivariate sensitivity analyses on key inputs. Results. With current access, we projected 2.95 CS cases/1000 LB, 0.29 HIV infections/1000 LB, 7.1% HIV MTCT risk, and 11.11 intrauterine fetal demises (IUFD)/1000 pregnancies, with significant regional variation. With ideal access, we projected improved outcomes: 1.00 CS cases/1000 LB, 0.10 HIV infections/1000 LB, HIV MTCT risk of 2.4%, and 10.65 IUFD/1000 pregnancies. Increased testing drove the greatest improvements. Even with ideal access, only HIV infections/1000 LB met elimination goals. Achieving all targets required testing and treatment >95% and reductions in prevalence and incidence of HIV and syphilis. Conclusions. Increasing access to care and HIV and syphilis antenatal testing will substantially reduce HIV and syphilis MTCT in Brazil. In addition, regionally tailored interventions reducing syphilis incidence and prevalence and supporting HIV treatment adherence are necessary to completely meet elimination goals. C1 [Cerda, Rodrigo; Francke, Jordan A.; Freedberg, Kenneth A.] Pan Amer Hlth Org, Div Gen Med, Washington, DC USA. [Perez, Freddy; Caffe, Sonja] Pan Amer Hlth Org, Communicable Dis & Hlth Anal Dept, HIV Hepatitis TB & Sexually Transmitted Infect Un, Washington, DC USA. [Domingues, Rosa Maria S. M.; Luz, Paula M.; Grinsztejn, Beatriz; Veloso, Valdilea G.] Fundacao Oswaldo Cruz, Inst Nacl Infectol Evandro Chagas, Rio De Janeiro, Brazil. [Francke, Jordan A.; Freedberg, Kenneth A.; Ciaranello, Andrea L.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Dept Med, Boston, MA 02114 USA. [Freedberg, Kenneth A.; Ciaranello, Andrea L.] Harvard Univ, Sch Publ Hlth, Div Infect Dis, Boston, MA 02115 USA. [Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Ciaranello, AL (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 50 Staniford St,Room 936, Boston, MA 02114 USA. EM aciaranello@partners.org NR 61 TC 1 Z9 1 U1 1 U2 3 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 SPR PY 2015 VL 2 IS 2 DI 10.1093/ofid/ofv073 PG 11 WC Infectious Diseases SC Infectious Diseases GA CX6BM UT WOS:000365786200005 ER PT J AU Naggie, S Patel, K Yang, LY Chow, SC Johnson, V Guyton, JR Muir, AJ Sulkowski, M Hicks, C AF Naggie, Susanna Patel, Keyur Yang, Lan-Yan Chow, Shein-Chung Johnson, Victoria Guyton, John R. Muir, Andrew J. Sulkowski, Mark Hicks, Charles TI Antiretroviral Effects on Host Lipoproteins Are Associated With Changes in Hepatitis C Virus (HCV) RNA Levels in Human Immunodeficiency Virus/HCV Coinfected Individuals SO OPEN FORUM INFECTIOUS DISEASES LA English DT Article DE apolipoprotein CIII; apolipoproteins; HCV; HCV RNA; HIV; lipoproteins ID HIV; INFECTION; THERAPY AB We evaluated the impact of antiretroviral-induced dyslipidemia on hepatitis C virus (HCV) biogenesis in human immunodeficiency virus (HIV)/HCV coinfected patients. This study used serum samples from antiretroviral-naive HIV/HCV patients initiating their first regimen as part of AIDS Clinical Trials Group study protocols (A5142, A5202). Initiation of antiretrovirals increased most lipoproteins and apolipoproteins. In the multivariable model, changes in apolipoproteins were associated with changes in log(10) HCV RNA from baseline to week-24 of therapy. Off-target lipogenic changes need to be considered in the context of liver and other metabolic disease in HIV/HCV patients. C1 [Naggie, Susanna; Patel, Keyur; Muir, Andrew J.] Duke Clin Res Inst, Durham, NC USA. [Naggie, Susanna; Patel, Keyur; Guyton, John R.; Muir, Andrew J.] Duke Univ, Med Ctr, Durham, NC USA. [Yang, Lan-Yan; Chow, Shein-Chung] Duke Dept Biostat & Bioinformat, Durham, NC USA. [Yang, Lan-Yan] Chang Gung Mem Hosp, Clin Trial Ctr, Taoyuan, Taiwan. [Johnson, Victoria] Birmingham VA Med Ctr, Birmingham, AL USA. [Johnson, Victoria] Univ Alabama, Tuscaloosa, AL 35487 USA. [Sulkowski, Mark] Johns Hopkins Univ, Baltimore, MD USA. [Hicks, Charles] Univ Calif San Diego, La Jolla, CA 92093 USA. RP Naggie, S (reprint author), 2400 Pratt St,Rm 0311,Terrace Level, Durham, NC 27705 USA. EM susanna.naggie@duke.edu NR 14 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 SPR PY 2015 VL 2 IS 2 DI 10.1093/ofid/ofv066 PG 5 WC Infectious Diseases SC Infectious Diseases GA CX6BM UT WOS:000365786200035 ER PT J AU Ouyang, ZY Buzon, MJ Zheng, L Sun, H Yu, XG Bosch, RJ Mellors, JW Eron, JJ Gandhi, RT Lichterfeld, M AF Ouyang, Zhengyu Buzon, Maria J. Zheng, Lu Sun, Hong Yu, Xu G. Bosch, Ronald J. Mellors, John W. Eron, Joseph J. Gandhi, Rajesh T. Lichterfeld, Mathias TI Transcriptional Changes in CD8(+) T Cells During Antiretroviral Therapy Intensified With Raltegravir SO OPEN FORUM INFECTIOUS DISEASES LA English DT Article DE antiretroviral therapy; CD8 T cells; gene expression profiling; HIV-1; raltegravir ID SET ENRICHMENT ANALYSIS; HIV-INFECTED PATIENTS; CONTROLLED-TRIAL; ACTIVATION; VIREMIA; REPLICATION; IDENTIFICATION; SUPPRESSION; LOADS AB Background. Intensification of antiretroviral therapy with raltegravir does not affect levels of residual human immunodeficiency virus (HIV)-1 viremia, but it has led to increased levels of episomal HIV-1 DNA in some patients, suggesting antiviral activity against otherwise unresponsive components of the viral reservoir. Effects of raltegravir on host cells remain less well understood. Methods. We used comprehensive and unbiased microarray-based transcriptional profiling to analyze gene expression changes in CD8(+) T cells from participants in a randomized clinical trial (AIDS Clinical Trials Group [ACTG] A5244) comparing raltegravir-intensified to nonintensified antiretroviral therapy. Results. Although raltegravir intensification failed to induce statistically significant changes in HIV-1 DNA or residual plasma viremia, we observed significant increases in the expression intensity of 121 host gene transcripts. In functional annotations of these transcripts, we found that they were mainly involved in glucose and carbohydrate metabolism, immune regulation, control of cell proliferation, and tumor suppression. Two of the raltegravir-responsive gene transcripts were statistically correlated with levels of residual HIV-1 RNA, but none of the remaining 119 transcripts were associated with immunologic or virologic characteristics of the study patients. Conclusions. Together, these findings demonstrate that raltegravir intensification can induce previously unrecognized, statistically significant gene expression changes in host CD8(+) T lymphocytes. C1 [Ouyang, Zhengyu; Buzon, Maria J.; Sun, Hong; Yu, Xu G.; Gandhi, Rajesh T.] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Buzon, Maria J.; Gandhi, Rajesh T.; Lichterfeld, Mathias] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Zheng, Lu; Bosch, Ronald J.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Mellors, John W.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA 15260 USA. [Eron, Joseph J.] Univ N Carolina, Div Infect Dis, Chapel Hill, NC USA. RP Lichterfeld, M (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM mlichterfeld@partners.org OI Buzon, Maria Jose/0000-0003-4427-9413 NR 37 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 SPR PY 2015 VL 2 IS 2 DI 10.1093/ofid/ofv045 PG 7 WC Infectious Diseases SC Infectious Diseases GA CX6BM UT WOS:000365786200039 ER PT J AU Siedner, MJ Campbell, JI Kanters, S Bennett, JE Thorlund, K Tsai, AC Mills, EJ AF Siedner, Mark J. Campbell, Jeffrey I. Kanters, Steve Bennett, John E. Thorlund, Kristian Tsai, Alexander C. Mills, Edward J. TI Combination Therapy for Human Immunodeficiency Virus-Associated Cryptococcal Meningitis: Whom, When, and Where? SO OPEN FORUM INFECTIOUS DISEASES LA English DT Letter ID ANTIFUNGAL C1 [Siedner, Mark J.; Campbell, Jeffrey I.; Tsai, Alexander C.] Harvard Univ, Sch Med, Boston, MA USA. [Siedner, Mark J.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Siedner, Mark J.; Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Kanters, Steve; Mills, Edward J.] Univ Ottawa, Fac Hlth Sci, Ottawa, ON K1N 6N5, Canada. [Kanters, Steve] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada. [Bennett, John E.] NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Thorlund, Kristian] McMaster Univ, Fac Hlth Sci, Hamilton, ON, Canada. [Tsai, Alexander C.] Massachusetts Gen Hosp, Div Global Psychiat, Boston, MA 02114 USA. [Tsai, Alexander C.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Mills, Edward J.] Stanford Univ, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. RP Siedner, MJ (reprint author), 55 Fruit St,GRJ5, Boston, MA 02114 USA. EM msiedner@partners.org NR 7 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 SPR PY 2015 VL 2 IS 2 DI 10.1093/ofid/ofv071 PG 2 WC Infectious Diseases SC Infectious Diseases GA CX6BM UT WOS:000365786200045 ER PT J AU Lee, W Yagel, S Cohen, SM Benacerraf, BR Cuckle, H Kagan, KO Van den Veyver, I Wapner, R AF Lee, Wesley Yagel, Simcha Cohen, Sarah M. Benacerraf, Beryl R. Cuckle, Howard Kagan, Karl O. Van den Veyver, Ignatia Wapner, Ron TI Noninvasive Prenatal Testing and Fetal Sonographic Screening Roundtable Discussion SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Editorial Material ID MATERNAL PLASMA; DNA; DIAGNOSIS; ANEUPLOIDY; COST; AMNIOCENTESIS; RISK; CARE C1 [Lee, Wesley] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Yagel, Simcha; Cohen, Sarah M.] Hadassah Hebrew Univ Med Ctr, Dept Obstet & Gynecol, IL-91240 Jerusalem, Israel. [Benacerraf, Beryl R.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Benacerraf, Beryl R.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Benacerraf, Beryl R.] Harvard Univ, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Sch Med, Boston, MA USA. [Cuckle, Howard] Univ Leeds, Dept Reprod Epidemiol, Leeds, W Yorkshire, England. [Kagan, Karl O.] Univ Tubingen, Dept Obstet & Gynecol, Tubingen, Germany. [Van den Veyver, Ignatia] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. [Van den Veyver, Ignatia] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Wapner, Ron] Columbia Univ Coll Phys & Surg, Dept Obstet & Gynecol, New York, NY 10032 USA. RP Yagel, S (reprint author), Hadassah Hebrew Univ Med Ctr, Dept Obstet & Gynecol, POB 24035, IL-91240 Jerusalem, Israel. EM simcha.yagel@gmail.com NR 35 TC 1 Z9 1 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 EI 1550-9613 J9 J ULTRAS MED JI J. Ultrasound Med. PD MAR 1 PY 2015 VL 34 IS 3 BP 363 EP 369 DI 10.7863/ultra.34.3.363 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA CS1PS UT WOS:000361840100001 ER PT J AU Benacerraf, BR Groszmann, Y Hornstein, MD Bromley, B AF Benacerraf, Beryl R. Groszmann, Yvette Hornstein, Mark D. Bromley, Bryann TI Deep Infiltrating Endometriosis of the Bowel Wall The Comet Sign SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE bowel; cul-de-sac; endometriosis; gynecologic ultrasound; pelvic pain; sonography ID GUIDED TRANSVAGINAL ULTRASONOGRAPHY; PELVIC ENDOMETRIOSIS; DIAGNOSTIC-ACCURACY; SLIDING SIGN; SONOGRAPHY; ULTRASOUND; OBLITERATION; PREDICTION; LOCATION; RECTUM AB The purpose of this study was to evaluate the appearance of deep infiltrating endometriosis of the bowel wall in the cul-de-sac and determine the characteristic appearance of these lesions. We searched our database between January 1, 2011, and December 31, 2013, for all patients who had sonographic findings of suspected deep infiltrating endometriosis of the bowel with obliteration of the cul-de-sac. The medical record of each patient was examined retrospectively for evidence of surgical confirmation of disease. The sonographic appearance, shape, and size of the bowel wall lesions were evaluated to develop criteria for deep infiltrating endometriosis of the rectosigmoid and cul-de-sac. The search of our database revealed 35 patients with sonographic findings of pelvic bowel wall endometriosis associated with obliteration of the cul-de-sac. Ten of these patients had surgical confirmation of bowel wall endometriosis after the scan, and another 4 patients had surgical evidence of endometriosis from prior surgery. All of the patients who underwent surgery subsequent to sonography had confirmation of their bowel wall infiltrative endometriosis. Sonographically, the bowel lesions were solid, focal, and tubular with slightly irregular margins and in most cases a thinner section or a "tail" at one end, resembling a comet. This study confirms that bowel wall implants have a very characteristic appearance, and extending the transvaginal examination to include an evaluation of the rectosigmoid seeking these bowel lesions is valuable, especially in any patient presenting with a history of pelvic pain. C1 [Benacerraf, Beryl R.; Groszmann, Yvette; Bromley, Bryann] Diagnost Ultrasound Associates PC, Boston, MA USA. [Benacerraf, Beryl R.; Bromley, Bryann] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Benacerraf, Beryl R.; Groszmann, Yvette; Hornstein, Mark D.; Bromley, Bryann] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Benacerraf, Beryl R.; Bromley, Bryann] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. RP Benacerraf, BR (reprint author), Diagnost Ultrasound Associates PC, 1 Brookline Pl, Brookline, MA 02445 USA. EM bbsono@aol.com NR 19 TC 7 Z9 7 U1 0 U2 1 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 EI 1550-9613 J9 J ULTRAS MED JI J. Ultrasound Med. PD MAR 1 PY 2015 VL 34 IS 3 BP 537 EP 542 DI 10.7863/ultra.34.3.537 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA CS1PS UT WOS:000361840100020 PM 25715375 ER PT J AU Byne, W AF Byne, William TI LGBT Health: Going Strong as We Begin Our Second Year SO LGBT HEALTH LA English DT Editorial Material DE cancer; Department of Health and Human Services (HHS); disorders of sex development (DSD); Institute of Medicine (IOM); intersex; LGBT health; LGBT rights; National Institutes of Health (NIH); pre-exposure prophylaxis (PrEP) C1 [Byne, William] Icahn Sch Med, Dept Psychiat, Bronx, NY USA. [Byne, William] James J Peters VAMC, Bronx, NY 10467 USA. RP Byne, W (reprint author), James J Peters VAMC, Dept Psychiat, Res Bldg,Room 2F39,130 West Kingsbridge Rd, Bronx, NY 10467 USA. EM william.byne@mssm.edu NR 2 TC 0 Z9 0 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 MAR PY 2015 VL 2 IS 1 BP 1 EP 2 DI 10.1089/lgbt.2015.0010 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CR9QU UT WOS:000361692500001 PM 26790010 ER PT J AU Byne, W Reiner, W AF Byne, William Reiner, William TI Interview with William Reiner, MD, Urologist and Child Psychiatrist, on Approaches to Care for Individuals with Disorders of Sex Development and Somatic Intersex Conditions SO LGBT HEALTH LA English DT Editorial Material DE assigned gender; disorders of sex development (DSD); intersex; optimal gender policy C1 [Byne, William] Icahn Sch Med, Dept Psychiat, Bronx, NY USA. [Byne, William] James J Peters VA Med Ctr, Bronx, NY 10467 USA. [Reiner, William] Univ Oklahoma, Hlth Sci Ctr, Dept Pediat Urol, Pediat Urol, Oklahoma City, OK USA. RP Byne, W (reprint author), James J Peters VAMC, Dept Psychiat, Res Bldg,Room 2F39,130 West Kingsbridge Rd, Bronx, NY 10467 USA. EM william.byne@mssm.edu NR 0 TC 0 Z9 0 U1 1 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 MAR PY 2015 VL 2 IS 1 BP 3 EP 10 DI 10.1089/lgbt.2015.0008 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CR9QU UT WOS:000361692500002 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI RETURN TO THE LAND OF THE HEAD HUNTERS: Edward S. Curtis, the Kwakwuka'wakw, and the Making of Modern Cinema SO JOURNAL OF THE WEST LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mifflin, Jeffrey] McLean Hosp, Belmont, MA USA. [Mifflin, Jeffrey] MIT, Cambridge, MA 02139 USA. [Mifflin, Jeffrey] Harvard Univ, Sch Business, Cambridge, MA 02138 USA. [Mifflin, Jeffrey] Massachusetts Med Soc, Waltham, MA USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 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 SPR PY 2015 VL 54 IS 2 BP 68 EP 70 PG 3 WC History SC History GA CP4UI UT WOS:000359877700007 ER PT J AU Thurmond, P Yang, JH Li, YD Lerner, LB Azadzoi, KM AF Thurmond, Portia Yang, Jing-Hua Li, Yedan Lerner, Lori B. Azadzoi, Kazem M. TI Structural modifications of the prostate in hypoxia, oxidative stress, and chronic ischemia SO KOREAN JOURNAL OF UROLOGY LA English DT Article DE Fibrosis; Ischemia; Oxidative stress; Prostate ID LOWER URINARY-TRACT; NATURAL-HISTORY; PELVIC ISCHEMIA; HYPERPLASIA; SYMPTOMS; BLADDER; MEN; ASSOCIATION; VOLUME; RISK AB Purpose: Clinical studies have reported a correlation between pelvic ischemia and voiding dysfunction in elderly men. The aim of this study was to identify and compare prostate structural modifications in cultured cells and in a rabbit model after exposure to hypoxia, oxidative stress, and chronic ischemia. Materials and Methods: Cultured human prostate smooth muscle cells (SMCs), epithelial cells (ECs), and stromal cells (SCs) were incubated under normoxia, hypoxia, and oxidative stress conditions by use of a computerized oxycycler system. We developed a rabbit model of chronic prostate ischemia by creating aorto-iliac arterial atherosclerosis. Markers of oxidative stress were examined by using fluorometric analysis and enzyme immunoassay. Prostate structure was examined by using Masson's trichrome staining and transmission electron microscopy (TEM). Results: Lipid peroxidation was found in SMCs exposed to hypoxia and in all cell types exposed to oxidative stress. We identified protein oxidation in ECs exposed to hypoxia and in all cell types exposed to oxidative stress. Markers indicating oxidative damage were present in chronically ischemic rabbit prostate tissue. These reactions were associated with DNA damage. Prostate ischemia resulted in epithelial atrophy, loss of smooth muscle, and diffuse fibrosis. TEM showed swollen mitochondria with degraded cristae, loss of membrane, loss of Golgi bodies, degenerated nerves, and disrupted cell-to-cell junctions. Conclusions: Human prostate cells exhibited differential reactions to hypoxia and oxidative stress with widespread DNA damage. Structural modifications in ischemic prostate tissue were similar to those in cells exposed to oxidative stress. Structural changes due to ischemia and oxidative stress may contribute to prostatic noncompliance in aging men. C1 [Thurmond, Portia; Yang, Jing-Hua; Li, Yedan; Lerner, Lori B.; Azadzoi, Kazem M.] VA Boston Healthcare Syst, Dept Urol, Boston, MA 02130 USA. [Thurmond, Portia; Yang, Jing-Hua; Li, Yedan; Lerner, Lori B.; Azadzoi, Kazem M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Azadzoi, Kazem M.] VA Boston Healthcare Syst, Dept Pathol, Boston, MA 02130 USA. RP Azadzoi, KM (reprint author), VA Boston Healthcare Syst, Dept Urol, 150 South Huntington Ave,Bldg 1A,Room 315 151, Boston, MA 02130 USA. EM kazadzoi@bu.edu FU BLRD VA [I01 BX001428] NR 30 TC 2 Z9 4 U1 1 U2 3 PU KOREAN UROLOGICAL ASSOC PI SEOUL PA RM 103-1102, PARK TOWER OFFICETEL 5-19, YONGSAN-DONG, YONGSAN-GU, SEOUL, 140-904, SOUTH KOREA SN 2005-6737 EI 2005-6745 J9 KOREAN J UROL JI Korean J. Urol. PD MAR PY 2015 VL 56 IS 3 BP 187 EP 196 DI 10.4111/kju.2015.56.3.187 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA CN4ZO UT WOS:000358439300004 PM 25763122 ER PT J AU Kopacz, MS Connery, AL AF Kopacz, Marek S. Connery, April L. TI The Veteran Spiritual Struggle SO SPIRITUALITY IN CLINICAL PRACTICE LA English DT Article DE service members; spirituality; suicide; veterans ID POSTTRAUMATIC-STRESS-DISORDER; MILITARY VETERANS; SUICIDAL IDEATION; VIETNAM VETERANS; COMBAT VETERANS; WAR VETERANS; DEPRESSION; GUILT; RISK; PTSD AB Although a considerable body of literature has been devoted to examining the physical, psychological, and social needs of veterans after their return from deployment, relatively little is known about the spiritual struggles some veterans face. In this article, we review what we know about this spiritual struggle, highlight the relevance of spirituality in clinical practice, and show examples of how a veteran's spiritual struggle may simultaneously present alongside different suicide risk factors. Suggestions for handling this spiritual struggle are then made. C1 [Kopacz, Marek S.] US Dept Vet Affairs, VISN Ctr Excellence Suicide Prevent 2, Canandaigua, NY 14424 USA. [Connery, April L.] US Dept Vet Affairs, Canandaigua VA Med Ctr, Canandaigua, NY 14424 USA. RP Kopacz, MS (reprint author), US Dept Vet Affairs, VISN Ctr Excellence Suicide Prevent 2, 400 Ft Hill Ave, Canandaigua, NY 14424 USA. EM marek.kopacz@va.gov NR 75 TC 4 Z9 4 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 2326-4500 EI 2326-4519 J9 SPIRITUAL CLIN PRACT JI Spiritual. Clin. Pract. PD MAR PY 2015 VL 2 IS 1 BP 61 EP 67 DI 10.1037/scp0000059 PG 7 WC Psychology, Clinical SC Psychology GA CL5BJ UT WOS:000356974500010 ER PT J AU Kopacz, MS AF Kopacz, Marek S. TI Spirituality and Suicide Prevention: Charting a Course for Research and Clinical Practice SO SPIRITUALITY IN CLINICAL PRACTICE LA English DT Editorial Material DE service members; spirituality; suicide prevention; veterans ID MEDICINE AB In their commentary, Bryan, Graham, and Roberge (2015) examine how spirituality can be conceptualized as a protective factor against suicide. The commentary submitted by Currier, Kuhlman, and Smith (2015) offers a review of the extant literature examining the relationship between spirituality and suicidal behavior as well as several ethical considerations related to applying spirituality in clinical practice. The present article looks to add to these discussions by providing further insight into understandings of spirituality as well as suggest additional steps which could be useful in developing the applicability of spirituality to suicide prevention efforts targeting current and former military personnel. C1 US Dept Vet Affairs, VISN Ctr Excellence Suicide Prevent 2, Canandaigua, NY 14424 USA. RP Kopacz, MS (reprint author), US Dept Vet Affairs, VISN Ctr Excellence Suicide Prevent 2, 400 Ft Hill Ave, Canandaigua, NY 14424 USA. EM marek.kopacz@va.gov NR 7 TC 0 Z9 0 U1 1 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 2326-4500 EI 2326-4519 J9 SPIRITUAL CLIN PRACT JI Spiritual. Clin. Pract. PD MAR PY 2015 VL 2 IS 1 BP 79 EP 81 DI 10.1037/scp0000062 PG 3 WC Psychology, Clinical SC Psychology GA CL5BJ UT WOS:000356974500013 ER PT J AU Yoon, J Liu, CF Lo, J Schectman, G Stark, R Rubenstein, LV Yano, EM AF Yoon, Jean Liu, Chuan-Fen Lo, Jeanie Schectman, Gordon Stark, Richard Rubenstein, Lisa V. Yano, Elizabeth M. TI Early Changes in VA Medical Home Components and Utilization SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID CLINICS AB Objectives: In 2010, the Veterans Health Administration (VA) began national implementation of its patient-centered medical home (PCMH) model, called Patient Aligned Care Teams (PACTs), to improve access, coordination, and patient-centered care. We evaluated changes in reported implementation of PCMH components in all VA primary care clinics, and patients' utilization of acute and non-acute care and total costs after 2 years. Study Design: Longitudinal study of 2,607,902 patients from 796 VA primary care clinics. Methods: Clinics were surveyed for their implementation of PCMH components. Patient outcomes were measured by outpatient visits for primary care, specialty care, telephone care, and emergency department (ED) care; hospitalizations for an ambulatory care-sensitive condition (ACSC); and costs of VA care in fiscal years (FYs) 2009 and 2011. Multi-level, multivariable models predicted changes in utilization and costs, adjusting for patients' health status, clinic PCMH component scores, and a patient fixed effect. Results: Clinics reported large improvements in adoption of all PCMH components from FY 2009 to FY 2011. Higher organization of practice scores was associated with fewer primary care visits (P =.012). Greater care coordination/transitions was modestly associated with more specialty care visits (P =.010) and fewer ED visits (P =.018), but quality/performance improvement was associated with more ED visits (P =.032). None of the PCMH components were significantly related to telephone visits, ACSC hospitalizations, or total healthcare costs. Conclusions: Improvements under organization of practice and care coordination/transitions appear to have impacted outpatient care, but reductions in acute care were largely absent. C1 [Yoon, Jean; Lo, Jeanie] VA Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, Menlo Pk, CA USA. [Yoon, Jean] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Menlo Pk, CA USA. [Liu, Chuan-Fen] VA Puget Sound, Ctr Innovat Vet Ctr & Value Driven Care, Seattle, WA USA. [Liu, Chuan-Fen] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Schectman, Gordon; Stark, Richard] Vet Hlth Adm, Patient Care Serv, Washington, DC USA. [Rubenstein, Lisa V.; Yano, Elizabeth M.] VA Greater Los Angeles, Ctr Innovat Study Healthcare Innovat Implementat, Sepulveda, CA USA. [Rubenstein, Lisa V.] RAND Corp, Santa Monica, CA USA. [Rubenstein, Lisa V.; Yano, Elizabeth M.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Rubenstein, Lisa V.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Yoon, J (reprint author), 795 Willow Rd,152 MPD, Menlo Pk, CA 94025 USA. EM jean.yoon@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Patient Care Services [XVA 65-018]; VA HSRD [RCS 05-195] FX This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Patient Care Services (XVA 65-018). Dr Yano's effort was covered by a VA HSR&D Senior Research Career Scientist Award (Project #RCS 05-195). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States federal government. NR 14 TC 1 Z9 1 U1 1 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 MAR PY 2015 VL 21 IS 3 BP 197 EP U142 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN7YF UT WOS:000358651300011 PM 25880624 ER PT J AU Prentice, JC Conlin, PR Gellad, WF Edelman, D Lee, TA Pizer, SD AF Prentice, Julia C. Conlin, Paul R. Gellad, Walid F. Edelman, David Lee, Todd A. Pizer, Steven D. TI Long-Term Outcomes of Analogue Insulin Compared With NPH for Patients With Type 2 Diabetes Mellitus SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID INSTRUMENTAL VARIABLES; COST-EFFECTIVENESS; VETERANS AFFAIRS; HEALTH-CARE; RISK; COMPLICATIONS; HYPOGLYCEMIA; MANAGEMENT; MORTALITY; MEDICARE AB Background: Long-acting insulin analogues (eg, insulin glargine and insulin detemir) are an alternative to neutral protamine Hagedorn (NPH) insulin for maintaining glycemic control in patients with diabetes. Clinical trials comparing analogue insulin and NPH have neither been adequately powered nor had sufficient follow-up to examine long-term health outcomes. Objectives: To compare the effects of NPH and long-acting insulin analogues on long-term outcomes. Study Design: This retrospective observational study relied on administrative data from the Veterans Health Administration and Medicare from 2000 to 2010. Local variations in analogue insulin prescribing rates were used in instrumental variable models to control for confounding. Outcomes were assessed using survival models. Methods: The study population included US veterans dually enrolled in Medicare who received at least 1 prescription for oral diabetes medication and then initiated long-acting insulin between 2001 and 2009. Outcomes included ambulatory care-sensitive condition (ACSC) hospitalizations and mortality. Results: There was no significant relationship between type of insulin and ACSC hospitalization or mortality. The hazard ratio for mortality of individuals starting a long-acting analogue insulin was 0.97 (95% CI, 0.85-1.11), and was 1.05 (95% CI, 0.95-1.16) for ACSC hospitalization. Differences in risk remained insignificant when predicting diabetes-specific ACSC hospitalizations, but starting on long-acting analogue insulin significantly increased the risk of a cardiovascular-specific ACSC hospitalization. Conclusions: We found no consistent difference in long-term health outcomes when comparing use of long-acting insulin analogues and NPH insulin. The higher cost of analogue insulin without demonstrable clinical benefit raises questions of its cost-effectiveness in the treatment of patients with diabetes. C1 [Prentice, Julia C.; Conlin, Paul R.; Pizer, Steven D.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Prentice, Julia C.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Conlin, Paul R.] Harvard Univ, Sch Med, Boston, MA USA. [Gellad, Walid F.] VA Pittsburgh Med Ctr, Pittsburgh, PA USA. [Gellad, Walid F.] Univ Pittsburgh, Pittsburgh, PA USA. [Edelman, David] VA Durham Med Ctr, Durham, NC USA. [Edelman, David] Duke Univ, Sch Med, Durham, NC USA. [Lee, Todd A.] Univ Illinois, Chicago, IL USA. [Pizer, Steven D.] Northeastern Univ, Boston, MA 02115 USA. RP Prentice, JC (reprint author), VA Boston Healthcare Syst, Hlth Care Financing & Econ, 150 So Huntington Ave 152H, Boston, MA 02130 USA. EM jprentic@bu.edu FU Health Services Research and Development Service of the US Department of Veterans Affairs [IIR 10-136]; AHRQ [R01 HS019708]; NIH [K24 DK63214] FX Health Services Research and Development Service of the US Department of Veterans Affairs (Grant No. IIR 10-136), AHRQ R01 HS019708, and NIH K24 DK63214. NR 39 TC 1 Z9 1 U1 0 U2 0 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 MAR PY 2015 VL 21 IS 3 BP E235 EP U78 PG 24 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CN7YF UT WOS:000358651300007 PM 26014311 ER PT J AU Trippa, L Waldron, L Huttenhower, C Parmigiani, G AF Trippa, Lorenzo Waldron, Levi Huttenhower, Curtis Parmigiani, Giovanni TI BAYESIAN NONPARAMETRIC CROSS-STUDY VALIDATION OF PREDICTION METHODS SO ANNALS OF APPLIED STATISTICS LA English DT Article DE Reproducibility; validation analysis; meta-analysis; random partitions; Bayesian nonparametrics; cancer signatures ID RANDOM-EFFECTS METAANALYSIS; GENE-EXPRESSION PROFILE; OVARIAN-CANCER; SURVIVAL; CHEMOTHERAPY; SIGNATURE; OUTCOMES; CLASSIFIERS; BOOTSTRAP; MODELS AB We consider comparisons of statistical learning algorithms using multiple data sets, via leave-one-in cross-study validation: each of the algorithms is trained on one data set; the resulting model is then validated on each remaining data set. This poses two statistical challenges that need to be addressed simultaneously. The first is the assessment of study heterogeneity, with the aim of identifying a subset of studies within which algorithm comparisons can be reliably carried out. The second is the comparison of algorithms using the ensemble of data sets. We address both problems by integrating clustering and model comparison. We formulate a Bayesian model for the array of cross-study validation statistics, which defines clusters of studies with similar properties and provides the basis for meaningful algorithm comparison in the presence of study heterogeneity. We illustrate our approach through simulations involving studies with varying severity of systematic errors, and in the context of medical prognosis for patients diagnosed with cancer, using high-throughput measurements of the transcriptional activity of the tumor's genes. C1 [Trippa, Lorenzo; Parmigiani, Giovanni] Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02115 USA. [Waldron, Levi] CUNY Hunter Coll, Sch Urban Publ Hlth, New York, NY 10035 USA. [Huttenhower, Curtis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Trippa, L (reprint author), Dana Farber Canc Inst, Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02115 USA. EM ltrippa@jimmy.harvard.edu; levi.waldron@hunter.cuny.edu; chuttenh@hsph.harvard.edu; gp@jimmy.harvard.edu OI Waldron, Levi/0000-0003-2725-0694 NR 45 TC 0 Z9 0 U1 4 U2 10 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 1932-6157 J9 ANN APPL STAT JI Ann. Appl. Stat. PD MAR PY 2015 VL 9 IS 1 BP 402 EP 428 DI 10.1214/14-AOAS798 PG 27 WC Statistics & Probability SC Mathematics GA CN3UX UT WOS:000358354400017 ER PT J AU Brewer, C Abernethy, A Currow, D Fearon, K Friend, J Temel, J AF Brewer, Cheryl Abernethy, Amy Currow, David Fearon, Kenneth Friend, John Temel, Jennifer TI EVALUATION OF ANOREXIA-CACHEXIA SYMPTOMS/CONCERNS FROM ROMANA 2, A PHASE III TRIAL OF ANAMORELIN IN NON-SMALL CELL LUNG CANCER PATIENTS WITH CACHEXIA. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 [Brewer, Cheryl; Abernethy, Amy] Duke Univ, Med Ctr, Durham, NC USA. [Currow, David] Flinders Univ S Australia, Adelaide, SA 5001, Australia. [Fearon, Kenneth] Western Gen Hosp, Edinburgh EH4 2XU, Midlothian, Scotland. [Friend, John] Helsinn Therapeut Inc, Bridgewater, NJ USA. [Temel, Jennifer] Massachusets Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X EI 1538-0688 J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2015 VL 42 IS 2 MA 71 BP E229 EP E229 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA CM7UF UT WOS:000357901300317 ER PT J AU Brock, J Barron, AM AF Brock, Jennifer Barron, Anne-Marie TI EXPLORATORY STUDY TO UNDERSTAND AUTO LOGOUS HEMATOPEOIETIC STEM CELL TRANSPLANT PATIENTS' EXPERIENCES OF HATHA YOGA. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 [Brock, Jennifer; Barron, Anne-Marie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Barron, Anne-Marie] Simmons Coll, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X EI 1538-0688 J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2015 VL 42 IS 2 MA 38 BP E215 EP E215 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA CM7UF UT WOS:000357901300284 ER PT J AU Cashavelly, B Blakeney, B Bursn-Britton, B Gorynski, K AF Cashavelly, Barbara Blakeney, Barbara Bursn-Britton, BettyAnn Gorynski, Kristen TI ENHANCING INPATIENT ONCOLOGY CARE BY REDUCING WAIT TIMES-NURSES DECREASE DOOR-TO-CHEMO TIMES. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 [Cashavelly, Barbara; Blakeney, Barbara; Bursn-Britton, BettyAnn; Gorynski, Kristen] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X EI 1538-0688 J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2015 VL 42 IS 2 BP E119 EP E120 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA CM7UF UT WOS:000357901300045 ER PT J AU Cronin, J Searle, F AF Cronin, Julie Searle, Frances TI INVESTIGATING THE IMPACT OF AN EDUCATIONAL PROGRAM ON NURSE'S ATTITUDES TOWARDS SEXUAL HEALTH CARE. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 [Cronin, Julie; Searle, Frances] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X EI 1538-0688 J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2015 VL 42 IS 2 MA 6 BP E202 EP E202 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA CM7UF UT WOS:000357901300252 ER PT J AU Gribbin, N Bowes, C AF Gribbin, Nicola Bowes, Cynthia TI RE-CHALLENGE AFTER PACLITAXEL-RELATED INFUSION REACTIONS IN AN ONCOLOGY INFUSION UNIT. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 [Gribbin, Nicola; Bowes, Cynthia] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X EI 1538-0688 J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2015 VL 42 IS 2 MA 46 BP E218 EP E219 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA CM7UF UT WOS:000357901300292 ER PT J AU Sipples, R Andan, C Eaby-Sandy, B AF Sipples, Rebecca Andan, Christine Eaby-Sandy, Beth TI PRACTICAL MANAGEMENT OF ADVERSE EVENTS ASSOCIATED WITH AFATINIB. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 [Sipples, Rebecca] Univ Alabama Birmingham, Birmingham, AL USA. [Andan, Christine] Dana Farber Canc Inst, Boston, MA 02115 USA. [Eaby-Sandy, Beth] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X EI 1538-0688 J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2015 VL 42 IS 2 MA 51 BP E220 EP E221 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA CM7UF UT WOS:000357901300297 ER PT J AU Albiges, L Fay, AP Xie, WL McDermott, DF Heng, DYC Dariane, C De Velasco, G Lester, RE Escudier, B Choueiri, TK AF Albiges, Laurence Fay, Andre Poisl Xie, Wanling McDermott, David F. Heng, Daniel Yick Chin Dariane, Charles De Velasco, Guillermo Lester, Renee Elizabeth Escudier, Bernard Choueiri, Toni K. TI Efficacy of targeted therapies after PD1/PD-L1 inhibitors in metastatic clear cell renal cell carcinoma (mRCC): A multi-institution retrospective cohort SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Univ Paris 11, Inst Gustave Roussy, Villejuif, France. HSL PUCRS, Oncol Serv, Porto Alegre, RS, Brazil. HSL PUCRS, Oncol Res Unit, Porto Alegre, RS, Brazil. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. Inst Gustave Roussy, Villejuif, France. Hosp Univ 12 Octubre, Med Oncol Serv, Madrid, Spain. Tom Baker Canc Clin, Calgary, AB, Canada. Inst Gustave Roussy, Villejuif, France. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 MAR 1 PY 2015 VL 33 IS 7 SU S MA 456 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700453 ER PT J AU Albiges, L Hakimi, AA Lin, X Simantov, R Zabor, EC Jacobsen, A Furberg, H Fay, AP Heng, DYC Signoretti, S McKay, RR Choueiri, TK AF Albiges, Laurence Hakimi, A. Ari Lin, Xun Simantov, Ronit Zabor, Emily C. Jacobsen, Anders Furberg, Helena Fay, Andre Poisl Heng, Daniel Yick Chin Signoretti, Sabina McKay, Rana R. Choueiri, Toni K. TI The impact of BMI on outcomes of patients with metastatic renal cell carcinoma treated with targeted therapy: An external validation data set and analysis of underlying biology from The Cancer Genome Atlas. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10021 USA. Pfizer Oncol, La Jolla, CA USA. Pfizer Oncol, New York, NY USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Pontificia Univ Catolica Rio Grande do Sul, HSL, Oncol Serv, Porto Alegre, RS, Brazil. Pontificia Univ Catolica Rio Grande do Sul, HSL, Oncol Res Unit, Porto Alegre, RS, Brazil. Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 MAR 1 PY 2015 VL 33 IS 7 SU S MA 405 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700402 ER PT J AU Alimohamed, NS Templeton, AJ Knox, JJ Lin, X Simantov, R Xie, WL Lawrence, NJ Broom, RJ Fay, AP Rini, BI Bjarnason, GA Smoragiewicz, M Kollmannsberger, CK Kanesvaran, R Wells, C Amir, E Choueiri, TK Heng, DYC AF Alimohamed, Nimira S. Templeton, Arnoud J. Knox, Jennifer J. Lin, Xun Simantov, Ronit Xie, Wanling Lawrence, Nicola Jane Broom, Reuben James Fay, Andre Poisl Rini, Brian I. Bjarnason, Georg A. Smoragiewicz, Martin Kollmannsberger, Christian K. Kanesvaran, Ravindran Wells, Connor Amir, Eitan Choueiri, Toni K. Heng, Daniel Yick Chin TI Change in neutrophil to lymphocyte ratio as a prognostic and predictive marker in response to targeted therapy for metastatic renal cell carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Tom Baker Canc Clin, Calgary, AB, Canada. Kantonsspital, St Gallen, Switzerland. Univ Toronto, Univ Hlth Network, Princess Margaret Canc Ctr, Dept Med Oncol, Toronto, ON, Canada. Pfizer Oncol, La Jolla, CA USA. Pfizer Oncol, New York, NY USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Auckland City Hosp, Auckland, New Zealand. Pontificia Univ Catolica Rio Grande do Sul, HSL, Oncol Serv, Porto Alegre, RS, Brazil. Pontificia Univ Catolica Rio Grande do Sul, HSL, Oncol Res Unit, Porto Alegre, RS, Brazil. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. BC Canc Agcy, Vancouver, BC, Canada. BC Canc Agcy, Vancouver Canc Ctr, Vancouver, BC, Canada. Natl Canc Ctr Singapore, Singapore, Singapore. Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. Univ Toronto, Dept Med, Princess Margaret Canc Ctr, Univ Hlth Network, Toronto, ON, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. OI Alimohamed, Nimira/0000-0002-2930-4206 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 404 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700401 ER PT J AU Bellmunt, J Guo, GW Mullane, SA Orsola, A Werner, L Van Hummelen, P Thorner, A Loda, M Choueiri, TK Barletta, JA Kwiatkowski, DJ Meyerson, M Van Allen, EM AF Bellmunt, Joaquim Guo, Guangwu Mullane, Stephanie A. Orsola, Anna Werner, Lillian Van Hummelen, Paul Thorner, Aaron Loda, Massimo Choueiri, Toni K. Barletta, Justine A. Kwiatkowski, David J. Meyerson, Matthew Van Allen, Eliezer Mendel TI Genomic landscape of high-grade T1 micropapillary bladder tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Univ Hosp Mar, IMIM, Barcelona, Spain. Broad Inst, Cambridge, MA USA. Dana Farber Canc Inst, Bladder Canc Ctr, Brigham & Womens Canc Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp,MIT, Dana Farber Canc Inst,Sch Med,Broad Inst Harvard, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 MAR 1 PY 2015 VL 33 IS 7 SU S MA 299 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700299 ER PT J AU Choueiri, TK Michaelson, MD Posadas, EM Sonpavde, G McDermott, DF Walsh, MK Wall, KC Seon, BK Jivani, MA Adams, BJ Theuer, CP AF Choueiri, Toni K. Michaelson, M. Dror Posadas, Edwin M. Sonpavde, Guru McDermott, David F. Walsh, Meghara K. Wall, Kevin C. Seon, Ben K. Jivani, Manoj A. Adams, Bonne J. Theuer, Charles P. TI A phase Ib dose-escalation study of TRC105 (anti-endoglin antibody) in combination with axitinib in patients with metastatic renal cell carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. TRACON Pharmaceut Inc, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 426 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700423 ER PT J AU Curreri, SA Markt, SC Miller, R O'Donnell, E Bernard, BD Kamran, SC Albiges, L Wright, AA Sweeney, C Beard, C AF Curreri, Stephanie A. Markt, Sarah C. Miller, Rowan O'Donnell, Elizabeth Bernard, Brandon David Kamran, Sophia C. Albiges, Laurence Wright, Alexi A. Sweeney, Christopher Beard, Clair TI Bilateral testicular germ cell tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Canc Res, London SW3 6JB, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Radiat Oncol Program, Boston, MA USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 392 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700389 ER PT J AU De Bono, JS Smith, MR Saad, F Rathkopf, DE Mulders, PFA Small, EJ Shore, ND Fizazi, K De Porre, P San Kheoh, T Li, JH Todd, MB Griffin, TW Ryan, CJ AF De Bono, Johann Sebastian Smith, Matthew Raymond Saad, Fred Rathkopf, Dana E. Mulders, Peter F. A. Small, Eric Jay Shore, Neal D. Fizazi, Karim De Porre, Peter San Kheoh, Thian Li, Jinhui Todd, Mary Beth Griffin, Thomas W. Ryan, Charles J. TI Response to taxane chemotherapy as first subsequent therapy after abiraterone acetate (AA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Post-hoc analysis of COU-AA-302. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Royal Marsden Hosp, Inst Canc Res, Sutton, Surrey, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Montreal, Montreal, PQ, Canada. Mem Sloan Kettering Canc Ctr, Weill Cornell Med Coll, New York, NY 10021 USA. Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. Carolina Urol Res Ctr, Myrtle Beach, SC USA. Univ Paris 11, Inst Gustave Roussy, Paris, France. Janssen Res & Dev, Beerse, Belgium. Janssen Res & Dev, Los Angeles, CA USA. Johnson & Johnson Med China, Shanghai, Peoples R China. Janssen Global Serv, Raritan, NJ USA. RI Mulders, Peter/H-8076-2014 NR 0 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 184 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700186 ER PT J AU Efstathiou, JA Lin, CC Gray, PJ Jemal, A AF Efstathiou, Jason Alexander Lin, Chun Chieh Gray, Phillip John Jemal, Ahmedin TI Androgen deprivation with or without radiation therapy for clinically node-positive prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Amer Canc Soc, Atlanta, GA 30329 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 198 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700199 ER PT J AU Fung, C Feldman, DR Hamilton, RJ Case-Eads, S Vaughn, DJ Beard, C Moore, MJ Sahasrabudhe, DM Brames, MJ Fossa, SD Sesso, HD Einhorn, LH The, LBTF AF Fung, Chunkit Feldman, Darren Richard Hamilton, Robert James Case-Eads, Somer Vaughn, David J. Beard, Clair Moore, Malcolm J. Sahasrabudhe, Deepak M. Brames, Mary J. Fossa, Sophie D. Sesso, Howard D. Einhorn, Lawrence H. The, Lois B. Travis For CA Platinum Study Grp TI Cardiovascular disease (CVD) risk factors among cisplatin-treated testicular cancer survivors (TCS): A multicenter clinical study of US and Canadian patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Univ Rochester, Med Ctr, Wilmot Canc Ctr, Rochester, NY 14642 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Toronto, Princess Margaret Hosp, Div Surg Oncol, Toronto, ON, Canada. Indiana Univ, Indianapolis, IN 46204 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Princess Margaret Canc Ctr, Toronto, ON, Canada. Univ Rochester, Wilmot Canc Ctr, Rochester, NY USA. Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Oslo Univ Hosp, Dept Oncol, N-0450 Oslo, Norway. Univ Oslo, Oslo, Norway. Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. Univ Rochester, Sch Med & Dent, Rochester, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 391 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700388 ER PT J AU Gan, HK Lickliter, J Millward, M Gu, Y Su, WG Qi, C Mu, H Frigault, M Morgan, S Gardner, HA Albiges, L Pal, SK Burris, HA Choueiri, TK AF Gan, Hui Kong Lickliter, Jason Millward, Michael Gu, Yi Su Weiguo Qi, Chuan Mu, Hua Frigault, Melanie Morgan, Shethah Gardner, Humphrey Athelstan Albiges, Laurence Pal, Sumanta Kumar Burris, Howard A. Choueiri, Toni K. TI cMet: Results in papillary renal cell carcinoma of a phase I study of AZD6094/volitinib leading to a phase 2 clinical trial with AZD6094/volitinib in patients with advanced papillary renal cell cancer (PRCC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Austin Hlth, Heidelberg, Germany. Nucleus Network Ltd, Melbourne, Vic, Australia. Univ Western Australia, Perth, WA 6009, Australia. Hutchison MediPharma, Shanghai, Peoples R China. AstraZeneca, Boston, MA USA. AstraZeneca, Macclesfield, Cheshire, England. AstraZeneca, Waltham, MA USA. Univ Paris Sud, Inst Gustave Roussy, Villejuif, France. City Hope Natl Med Ctr, Duarte, CA USA. PLLC, Tennessee Oncol, Sarah Cannon Res Inst, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 MAR 1 PY 2015 VL 33 IS 7 SU S MA 487 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700484 ER PT J AU Gerke, T Tyekucheva, S Penney, K Sweeney, C Lis, R Sesso, HD Nuttall, E Loda, M Stampfer, MJ Parmigiani, G Mucci, LA AF Gerke, Travis Tyekucheva, Svitlana Penney, Kathryn Sweeney, Christopher Lis, Rosina Sesso, Howard D. Nuttall, Elizabeth Loda, Massimo Stampfer, Meir J. Parmigiani, Giovanni Mucci, Lorelei A. TI Discovery and validation of a 30-gene expression signature to identify prostate cancer patients who are candidates for active surveillance SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Univ Florida, Gainesville, FL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 10 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700011 ER PT J AU Giannatempo, P Pond, GR Sonpavde, G Albany, C Loriot, Y Sweeney, C Cary, KC Salvioni, R Colecchia, M Nicolai, N Raggi, D El Mouallem, NR Feldman, H Fizazi, K Einhorn, LH Necchi, A AF Giannatempo, Patrizia Pond, Gregory Russell Sonpavde, Guru Albany, Costantine Loriot, Yohann Sweeney, Christopher Cary, Kelly Clint Salvioni, Roberto Colecchia, Maurizio Nicolai, Nicola Raggi, Daniele El Mouallem, Nemer Robert Feldman, Hope Fizazi, Karim Einhorn, Lawrence H. Necchi, Andrea TI Treatment and clinical outcomes of patients with teratoma with somatic-type malignant transformation (TMT): An international collaboration. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Fdn IRCCS Ist Nazl Tumori, Milan, Italy. McMaster Univ, Hamilton, ON, Canada. Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Gustave Roussy, Villejuif, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Indiana Univ Sch Med, Dept Urol, Indianapolis, IN 46202 USA. Univ Paris Sud, Inst Gustave Roussy, Villejuif, France. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 375 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700099 ER PT J AU Graff, JN Baciarello, G Armstrong, AJ Higano, CS Iversen, P Forer, D Mansbach, HH Phung, D Tombal, BF Beer, TM Sternberg, CN AF Graff, Julie Nicole Baciarello, Giulia Armstrong, Andrew J. Higano, Celestia S. Iversen, Peter Forer, David Mansbach, Harry H. Phung, De Tombal, Bertrand F. Beer, Tomasz M. Sternberg, Cora N. TI Clinical outcomes and safety in men >= 75 and < 75 years with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide in the phase 3 PREVAIL trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Portland VA Med Ctr, OHSU Knight Canc Inst, Portland, OR USA. Grand Paris, Dept Canc Med, Gustave Roussy, Villejuif, France. Duke Univ, Durham, NC USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark. Medivation Inc, San Francisco, CA USA. Astellas Pharma Global Dev Inc, Leiderdorp, Netherlands. Clin Univ St Luc, Div Urol, B-1200 Brussels, Belgium. Oregon Hlth & Sci Univ, OHSU Knight Canc Inst, Portland, OR 97201 USA. Hosp San Camillo Forlanini, Rome, Italy. NR 0 TC 1 Z9 1 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 MAR 1 PY 2015 VL 33 IS 7 SU S MA 200 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700201 ER PT J AU Gray, PJ Lin, CC Jemal, A Efstathiou, JA AF Gray, Phillip John Lin, Chun Chieh Jemal, Ahmedin Efstathiou, Jason Alexander TI Temporal trends in the management of localized prostate cancer: From 2004 to 2011. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Amer Canc Soc, Atlanta, GA 30329 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 42 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700044 ER PT J AU Haas, NB Manola, J Uzzo, RG Atkins, MB Wilding, G Pins, M Jewett, MAS Kane, CJ Cella, D Wagner, LI Coomes, B Wood, CG Dutcher, JP Flaherty, K DiPaola, RS AF Haas, Naomi B. Manola, Judith Uzzo, Robert G. Atkins, Michael B. Wilding, George Pins, Michael Jewett, Michael A. S. Kane, Christopher J. Cella, David Wagner, Lynne I. Coomes, Bob Wood, Christopher G. Dutcher, Janice P. Flaherty, Keith DiPaola, Robert S. TI Initial results from ASSURE (E2805): Adjuvant sorafenib or sunitinib for unfavorable renal carcinoma, an ECOG-ACRIN-led, NCTN phase III trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Lombardi Comprehens Canc Ctr, Washington, DC USA. Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. Univ Illinois, Coll Med, Chicago, IL USA. Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Our Lady Mercy Canc Ctr, Bronx, NY USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. Rutgers Biomed & Hlth Sci, New Brunswick, NJ USA. NR 0 TC 12 Z9 13 U1 0 U2 2 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 MAR 1 PY 2015 VL 33 IS 7 SU S MA 403 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700400 ER PT J AU Heng, DYC Wells, C Donskov, F Rini, BI Lee, JL Bjarnason, GA Beuselinck, B Smoragiewicz, M Alva, AS Srinivas, S Wood, L Yamamoto, H Ernst, DS Pal, SK Yuasa, T Broom, RJ Kanesvaran, R Bamias, A Knox, JJ Choueiri, TK AF Heng, Daniel Yick Chin Wells, Connor Donskov, Frede Rini, Brian I. Lee, Jae-Lyun Bjarnason, Georg A. Beuselinck, Benoit Smoragiewicz, Martin Alva, Ajjai Shivaram Srinivas, Sandy Wood, Lori Yamamoto, Haru Ernst, D. Scott Pal, Sumanta Kumar Yuasa, Takeshi Broom, Reuben James Kanesvaran, Ravindran Bamias, Aristotelis Knox, Jennifer J. Choueiri, Toni K. TI Third-line therapy in metastatic renal cell carcinoma: Results from the International mRCC Database Consortium. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark. Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. Univ Ulsan, Coll Med, Dept Oncol, Asan Med Ctr, Seoul, South Korea. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Univ Hosp Leuven, Dept Gen Med Oncol, Leuven, Belgium. BC Canc Agcy, Vancouver, BC, Canada. Univ Michigan, Ann Arbor, MI 48109 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. London Reg Canc Ctr, London, ON N6A 4L6, Canada. City Hope Natl Med Ctr, Duarte, CA USA. Japanese Fdn Canc Res, Dept Urol, Canc Inst Hosp, Tokyo, Japan. Auckland City Hosp, Auckland, New Zealand. Natl Canc Ctr Singapore, Singapore, Singapore. Univ Athens, Alexandra Gen Hosp Athens, Dept Oncol, Dept Clin Therapeut, Athens, Greece. Univ Toronto, Dept Med Oncol, Princess Margaret Canc Ctr, Univ Hlth Network, Toronto, ON, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 MAR 1 PY 2015 VL 33 IS 7 SU S MA 430 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700427 ER PT J AU Kaffenberger, SD Ciriello, G Winer, AG Voss, MH Maranchie, JK Tamboli, P Rathmell, K Choueiri, TK Motzer, RJ Coleman, JA Russo, P Hsieh, J Hakimi, AA AF Kaffenberger, Samuel D. Ciriello, Giovanni Winer, Andrew G. Voss, Martin Henner Maranchie, Jodi Kathleen Tamboli, Pheroze Rathmell, Kimryn Choueiri, Toni K. Motzer, Robert J. Coleman, Jonathan A. Russo, Paul Hsieh, James Hakimi, A. Ari TI Proteomic stratification of clear cell renal cell carcinoma utilizing The Cancer Genome Atlas (TCGA) with external validation. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ N Carolina, Chapel Hill, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 MAR 1 PY 2015 VL 33 IS 7 SU S MA 406 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700403 ER PT J AU Kaymakcalan, MD Xie, WL Albiges, L North, SA Kollmannsberger, CK Smoragiewicz, M Kroeger, N Wells, C Rha, SY Lee, JL Fay, AP Heng, DYC Choueiri, TK AF Kaymakcalan, Marina Dusevic Xie, Wanling Albiges, Laurence North, Scott A. Kollmannsberger, Christian K. Smoragiewicz, Martin Kroeger, Nils Wells, Connor Rha, Sun Young Lee, Jae-Lyun Fay, Andre Poisl Heng, Daniel Yick Chin Choueiri, Toni K. TI Risk factors and a model to predict toxicity-related treatment discontinuation in patients with metastatic renal cell carcinoma treated with VEGF-targeted therapy: Results from the International Metastatic RCC Database Consortium SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Univ Paris 11, Inst Gustave Roussy, Villejuif, France. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. BC Canc Agcy, Vancouver Canc Ctr, Vancouver, BC, Canada. BC Canc Agcy, Vancouver, BC, Canada. Univ Med Greifswald, Dept Urol, Greifswald, Germany. Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. Yonsei Univ, Coll Med, Seoul, South Korea. Univ Ulsan, Coll Med, Dept Oncol, Asan Med Ctr, Seoul, South Korea. HSL PUCRS, Oncol Serv, Porto Alegre, RS, Brazil. HSL PUCRS, Oncol Res Unit, Porto Alegre, RS, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 464 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700461 ER PT J AU Kennedy, MW Carter, J Wright, S Contreras, M Winkfield, KM AF Kennedy, Mark Wendell Carter, Jacques Wright, Stephen Contreras, Magnolia Winkfield, Karen Marie TI A community-based approach to educating black men in underserved communities about the risks and benefits of prostate cancer screening. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Massachusetts Prostate Canc Coalit Inc, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Mattapan Community Hlth Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 99 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700102 ER PT J AU Mahal, BAV Aizer, AA Efstathiou, JA Nguyen, PL AF Mahal, Brandon Arvin Virgil Aizer, Ayal Aaron Efstathiou, Jason Alexander Nguyen, Paul Linh TI The association of very low PSA with increased cancer-specific death in men with high-grade prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 62 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700063 ER PT J AU Mak, KS Smith, A Eidelman, A Clayman, RH Cheng, JS Matthews, J Niemierko, A Nielsen, ME Feldman, AS Lee, RJ Zietman, AL Shipley, WU Chen, RC Milowsky, MI Efstathiou, JA AF Mak, Kimberley S. Smith, Angela Eidelman, Alec Clayman, Rebecca Helen Cheng, Jed-Sian Matthews, Jonathan Niemierko, Andrzej Nielsen, Matthew Edward Feldman, Adam S. Lee, Richard J. Zietman, Anthony L. Shipley, William U. Chen, Ronald C. Milowsky, Matthew I. Efstathiou, Jason Alexander TI Quality of life in long-term survivors of muscle-invasive bladder cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Harvard Radiat Oncol Program, Boston, MA USA. Univ N Carolina, Chapel Hill, NC USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 319 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700319 ER PT J AU Markt, SC Miller, R O'Donnell, E Albiges, L Bernard, BD Lago-Hernandez, C Curreri, SA Wright, AA Beard, C Sweeney, C AF Markt, Sarah C. Miller, Rowan O'Donnell, Elizabeth Albiges, Laurence Bernard, Brandon David Lago-Hernandez, Carlos Curreri, Stephanie A. Wright, Alexi A. Beard, Clair Sweeney, Christopher TI BMI at diagnosis and adverse outcomes among men with malignant testicular germ cell tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. Inst Canc Res, London SW3 6JB, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Paris Sud, Inst Gustave Roussy, Villejuif, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 400 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700397 ER PT J AU McGinley, KF Sun, XZ Howard, LE Aronson, WJ Terris, MK Kane, CJ Amling, CL Cooperberg, MR Freedland, SJ AF McGinley, Kathleen F. Sun, Xizi Howard, Lauren E. Aronson, William J. Terris, Martha K. Kane, Christopher J. Amling, Christopher L. Cooperberg, Matthew R. Freedland, Stephen J. TI Utilization and impact of surgical technique on the performance of pelvic lymph node dissection at radical prostatectomy: Results from the SEARCH database. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Duke Univ, Med Ctr, Durham, NC USA. Duke Univ, Durham VA Med Ctr, Durham, NC USA. Duke Univ, Durham VA Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Georgia Regents Univ, Med Coll Georgia, Charles Norwood VA Med Ctr, Augusta, GA USA. Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 73 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700074 ER PT J AU McGinley, KF Sun, XZ Howard, LE Aronson, WJ Terris, MK Kane, CJ Amling, CL Cooperberg, MR Freedland, SJ AF McGinley, Kathleen F. Sun, Xizi Howard, Lauren E. Aronson, William J. Terris, Martha K. Kane, Christopher J. Amling, Christopher L. Cooperberg, Matthew R. Freedland, Stephen J. TI Can Gleason 7 prostate cancer ever be low-risk? Results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Duke Univ, Med Ctr, Durham, NC USA. Duke Univ, Durham VA Med Ctr, Durham, NC USA. Duke Univ, Durham VA Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Georgia Regents Univ, Charles Norwood VA Med Ctr, Med Coll Georgia, Augusta, GA USA. Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 57 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700058 ER PT J AU McKay, RR Lin, X Albiges, LK Fay, AP Kaymakcalan, MD Mickey, SS Ghoroghchian, PP Bhatt, RS Simantov, R Choueiri, TK Heng, DYC AF McKay, Rana R. Lin, Xun Albiges, Laurence K. Fay, Andre Poisl Kaymakcalan, Marina Dusevic Mickey, Suzanne S. Ghoroghchian, Paiman Peter Bhatt, Rupal Satish Simantov, Ronit Choueiri, Toni K. Heng, Daniel Yick Chin TI Impact of statins and survival outcomes in patients with metastatic renal cell carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Pfizer Oncol, La Jolla, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. HSL PUCRS, Oncol Serv, Porto Alegre, RS, Brazil. HSL PUCRS, Oncol Res Unit, Porto Alegre, RS, Brazil. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Pfizer Oncol, New York, NY USA. Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 435 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700432 ER PT J AU McKay, RR Choueiri, TK Werner, L Atkins, MB Olivier, KM Song, JX Signoretti, S McDermott, DF Michaelson, MD AF McKay, Rana R. Choueiri, Toni K. Werner, Lillian Atkins, Michael B. Olivier, Kara M. Song, Jiaxi Signoretti, Sabina McDermott, David F. Michaelson, M. Dror TI A phase II trial of sunitinib and gemcitabine in sarcomatoid and/or poor-risk patients with metastatic renal cell carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Lombardi Comprehens Canc Ctr, Washington, DC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 1 Z9 1 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 MAR 1 PY 2015 VL 33 IS 7 SU S MA 408 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700405 ER PT J AU Morris, MJ Higano, CS Scher, HI Sweeney, C Antonarakis, ES Shevrin, DH Ryan, CJ Lorlot, Y Fizazi, K Pandit-Taskar, N Garcia-Vargas, JE Lyseng, K Bloma, M Aksnes, AK Carrasquillo, JA AF Morris, Michael J. Higano, Celestia S. Scher, Howard I. Sweeney, Christopher Antonarakis, Emmanuel S. Shevrin, Daniel H. Ryan, Charles J. Lorlot, Yohann Fizazi, Karim Pandit-Taskar, Neeta Garcia-Vargas, Jose E. Lyseng, Kari Bloma, Marianne Aksnes, Anne-Kirsti Carrasquillo, Jorge A. TI Effects of radium-223 dichloride (Ra-223) with docetaxel (D) versus D on prostate-specific antigen (PSA) and bone alkaline phosphatase (bALP) in patients (pts) with castration-resistant prostate cancer (CRPC) and bone metastases (mets): A phase 1/2a clinical trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. NorthShore Univ HealthSyst, Evanston, IL USA. UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. Univ Paris 11, Inst Gustave Roussy, Villejuif, France. Bayer HealthCare, Whippany, NJ USA. Bayer Oslo, As, Norway. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 202 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700203 ER PT J AU O'Donnell, PH Plimack, ER Bellmunt, J Berger, R Montgomery, RB Heath, K Dolled-Filhart, M Pathiraja, K Gause, CK Cheng, JD Perini, RF Gupta, S AF O'Donnell, Peter H. Plimack, Elizabeth R. Bellmunt, Joaquim Berger, Raanan Montgomery, Robert B. Heath, Karl Dolled-Filhart, Marisa Pathiraja, Kumudu Gause, Christine K. Cheng, Jonathan D. Perini, Rodolfo F. Gupta, Shilpa TI Pembrolizumab (Pembro; MK-3475) for advanced urothelial cancer: Results of a phase IB study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Univ Chicago, Chicago, IL 60637 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. Univ Washington, Seattle, WA 98195 USA. Merck & Co Inc, Whitehouse Stn, NJ USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 296 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700296 ER PT J AU Paly, JJ Gray, PJ Lin, CC Sineshaw, H Jemal, A Efstathiou, JA AF Paly, Jonathan J. Gray, Phillip John Lin, Chun Chieh Sineshaw, Helmneh Jemal, Ahmedin Efstathiou, Jason Alexander TI Management and outcomes of clinical stage II a/b seminoma: Results from the National Cancer Database SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Amer Canc Soc, Atlanta, GA 30329 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 4 U2 4 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 MAR 1 PY 2015 VL 33 IS 7 SU S MA 378 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700376 ER PT J AU Ramos, J Casey, MF Crabb, SJ Bamias, A Harshman, LC Wong, YN Bellmunt, J De Giorgi, U Ladoire, S Powles, T Pal, SK Niegisch, G Sternberg, CN Alva, AS Agarwal, N Necchi, A Vaishampayan, UN Rosenberg, JE Galsky, MD Yu, EY AF Ramos, Jorge Casey, Martin Francis Crabb, Simon J. Bamias, Aristotelis Harshman, Lauren Christine Wong, Yu-Ning Bellmunt, Joaquim De Giorgi, Ugo Ladoire, Sylvain Powles, Thomas Pal, Sumanta Kumar Niegisch, Guenter Sternberg, Cora N. Alva, Ajjai Shivaram Agarwal, Neeraj Necchi, Andrea Vaishampayan, Ulka N. Rosenberg, Jonathan E. Galsky, Matt D. Yu, Evan Y. CA RISC Investigators TI Impact of chemotherapy (CTX) on venous thromboembolism (VTE) and prognostic implications in patients with metastatic urinary tract tumors (UTT). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Univ Washington, Sch Med, Seattle, WA USA. Icahn Sch Med Mt Sinai, New York, NY 10029 USA. Univ Southampton, Southampton, Hants, England. Univ Athens, Alexandra Gen Hosp Athens, Dept Oncol, Dept Clin Therapeut, Athens, Greece. Dana Farber Canc Inst, Boston, MA 02115 USA. Temple Univ Hlth Syst, Fox Chase Canc Ctr, Philadelphia, PA USA. IMIM, Univ Hosp del Mar, Barcelona, Spain. IRCCS, Ist Sci Romagnolo Studio & Cura Tumori, Meldola, Italy. Georges Francois Leclerc Canc Ctr, Dijon, France. Barts Hlth & Royal Free NHS Trust, Barts Canc Inst, London, England. City Hope Natl Med Ctr, Duarte, CA USA. Univ Dusseldorf, Dept Urol, Dusseldorf, Germany. Hosp San Camillo Forlanini, Rome, Italy. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Fdn IRCCS Ist Nazl Tumori, Milan, Italy. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 318 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700318 ER PT J AU Ryan, CJ Smith, MR Fizazi, K Saad, F Sternberg, CN Logothetis, C Small, EJ Carles, J Flaig, TW Taplin, ME Higano, CS De Souza, PL De Bono, JS Griffin, TW De Porre, P Park, YC Li, JH Kheoh, TS Molina, A Rathkopf, DE AF Ryan, Charles J. Smith, Matthew Raymond Fizazi, Karim Saad, Fred Sternberg, Cora N. Logothetis, Christopher Small, Eric Jay Carles, Joan Flaig, Thomas W. Taplin, Mary-Ellen Higano, Celestia S. De Souza, Paul L. De Bono, Johann Sebastian Griffin, Thomas W. De Porre, Peter Park, Youn Choi Li, Jinhui Kheoh, Thian San Molina, Arturo Rathkopf, Dana E. TI Impact of crossover and baseline prognostic factors on overall survival (OS) with abiraterone acetate (AA) in the COU-AA-302 final analysis. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Paris 11, Inst Gustave Roussy, Paris, France. Univ Montreal, Montreal, PQ, Canada. San Camillo & Forlanini Hosp, Rome, Italy. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Hosp Vall dHebron, Vall dHebron Inst Oncol, Barcelona, Spain. Univ Colorado, Sch Med, Ctr Canc, Aurora, CO USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Western Sydney, Sch Med, Liverpool, Australia. Ingham Inst, Liverpool, Australia. Royal Marsden Hosp, Inst Canc Res, Sutton, Surrey, England. Janssen Res & Dev, Los Angeles, CA USA. Janssen Res & Dev, Beerse, Belgium. Janssen Res & Dev, Raritan, NJ USA. Johnson & Johnson Med China, Shanghai, Peoples R China. Janssen Res & Dev, Menlo Pk, CA USA. Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 142 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700144 ER PT J AU Sartor, AO Fernandez, DC Morris, MJ Iagaru, A Brown, A Almeida, F Sweeney, C Smith, MR Dicker, A Wong, YN Shore, ND Gratt, J Petrenciuc, O Vogelzang, NJ AF Sartor, A. Oliver Fernandez, Daniel Celestino Morris, Michael J. Iagaru, Andrei Brown, Alan Almeida, Fabio Sweeney, Christopher Smith, Matthew Raymond Dicker, Adam Wong, Yu-Ning Shore, Neal D. Gratt, Jeremy Petrenciuc, Oana Vogelzang, Nicholas J. TI Prior and concurrent use of abiraterone and enzalutamide with Ra-223 in an expanded access setting. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Tulane Canc Ctr, New Orleans, LA USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Stanford Univ, Stanford, CA 94305 USA. 21st Century Oncol, Ft Myers, FL USA. Arizona Mol Imaging Ctr, Phoenix, AZ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Temple Univ Hlth Syst, Fox Chase Canc Ctr, Philadelphia, PA USA. Carolina Urol Res Ctr, Myrtle Beach, SC USA. Bayer HealthCare, Whippany, NJ USA. Comprehens Canc Ctr Nevada, Las Vegas, NV USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 253 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700254 ER PT J AU Smith, MR Brown, JE Fizazi, K Klotz, L Marx, GM Wang, H Warner, D Lipton, A AF Smith, Matthew Raymond Brown, Janet Elizabeth Fizazi, Karim Klotz, Laurence Marx, Gavin M. Wang, Huei Warner, Douglas Lipton, Allan TI Bone metabolism biomarkers in men with advanced prostate cancer (PC) and bone metastases treated with denosumab versus zoledronic acid (ZA). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Canc Res UK Clin Ctr, Leeds, W Yorkshire, England. Univ Paris Sud, Inst Gustave Roussy, Villejuif, France. Univ Toronto, Toronto, ON, Canada. Northern Haematol & Oncol Grp, Sydney, NSW, Australia. Amgen Inc, Thousand Oaks, CA 91320 USA. Amgen Inc, Dept Clin Dev, Thousand Oaks, CA 91320 USA. Penn State Milton S Hershey Med Ctr, Hershey, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 267 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700268 ER PT J AU Smith, MR De Bono, JS Sternberg, CN Le Moulec, S Oudard, S De Giorgi, U Krainer, M Bergman, AM Hoelzer, W De Wit, R Boegemann, M Saad, F Cruciani, G Thiery-Vuillemin, A Feyerabend, S Miller, K Ramies, DA Hessel, C Weitzman, A Fizazi, K AF Smith, Matthew Raymond De Bono, Johann Sebastian Sternberg, Cora N. Le Moulec, Sylvestre Oudard, Stephane De Giorgi, Ugo Krainer, Michael Bergman, Andre M. Hoelzer, Wolfgang De Wit, Ronald Boegemann, Martin Saad, Fred Cruciani, Giorgio Thiery-Vuillemin, Antoine Feyerabend, Susan Miller, Kurt Ramies, David Albert Hessel, Colin Weitzman, Aaron Fizazi, Karim TI Final analysis of COMET-1: Cabozantinib (Cabo) versus prednisone (Pred) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) previously treated with docetaxel (D) and abiraterone (A) and/or enzalutamide (E). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Royal Marsden Hosp NHS Fdn Trust, Inst Canc Res, Sutton, Surrey, England. Hosp San Camillo Forlanini, Rome, Italy. Val de Grace Hosp, Paris, France. Hop Europeen Georges Pompidou, Dept Med Oncol, Paris, France. IRCS Ist Sci Romagnolo Studio & Cura Tumori, Meldola, Italy. Med Univ Vienna, Vienna, Austria. Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. Univ Hosp Munster, Dept Urol, Munster, Germany. Univ Montreal, Ctr Hosp, CRCHUM, Montreal, PQ, Canada. Azienda USL, Med Oncol Dept, Ravenna, Italy. CHU Minjoz, Med Oncol Unit, Besancon, France. Charite, D-13353 Berlin, Germany. Exelixis Inc, San Francisco, CA USA. Univ Paris 11, Inst Gustave Roussy, Villejuif, France. NR 0 TC 16 Z9 16 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 MAR 1 PY 2015 VL 33 IS 7 SU S MA 139 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700141 ER PT J AU Sonpavde, G Pond, GR Rosenberg, JE Bajorin, DF Regazzi, AM Choueiri, TK Mullane, SA Niegisch, G Albers, P Necchi, A di Lorenzo, G Fougeray, R Galsky, MD Sridhar, SS Ko, YJ Milowsky, MI Bellmunt, J AF Sonpavde, Guru Pond, Gregory Russell Rosenberg, Jonathan E. Bajorin, Dean F. Regazzi, Ashley Marie Choueiri, Toni K. Mullane, Stephanie A. Niegisch, Guenter Albers, Peter Necchi, Andrea di Lorenzo, Giuseppe Fougeray, Ronan Galsky, Matt D. Sridhar, Srikala S. Ko, Yoo-Joung Milowsky, Matthew I. Bellmunt, Joaquim TI Improved prognostic classification of patients receiving salvage systemic therapy for advanced urothelial carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Univ Alabama Birmingham, Birmingham Comprehens Canc Ctr, Birmingham, AL USA. McMaster Univ, Hamilton, ON, Canada. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Bladder Canc Ctr, Boston, MA USA. Univ Dusseldorf, Dept Urol, Dusseldorf, Germany. Univ Dusseldorf, Dusseldorf, Germany. Fdn IRCCS Ist Nazl Tumori, Milan, Italy. Univ Naples Federico II, Dept Clin Med, Med Oncol Unit, Naples, Italy. Inst Rech Pierre Fabre, Boulogne, France. Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. Univ Toronto, Dept Med, Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 311 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700311 ER PT J AU Vogelzang, NJ Fernandez, DC Morris, MJ Iagaru, A Brown, A Almeida, F Sweeney, C Smith, MR Dicker, A Wong, YN Shore, ND Bangerter, K Petrenciuc, O Sartor, AO AF Vogelzang, Nicholas J. Fernandez, Daniel Celestino Morris, Michael J. Iagaru, Andrei Brown, Alan Almeida, Fabio Sweeney, Christopher Smith, Matthew Raymond Dicker, Adam Wong, Yu-Ning Shore, Neal D. Bangerter, Keith Petrenciuc, Oana Sartor, A. Oliver TI Radium-223 dichloride (Ra-223) in US expanded access program (EAP). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Comprehens Canc Ctr Nevada, Las Vegas, NV USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Stanford Univ, Stanford, CA 94305 USA. 21st Century Oncol, Ft Myers, FL USA. Arizona Mol Imaging Ctr, Phoenix, AZ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Temple Univ Hlth Syst, Fox Chase Canc Ctr, Philadelphia, PA USA. Carolina Urol Res Ctr, Myrtle Beach, SC USA. Bayer HealthCare, Whippany, NJ USA. Tulane Canc Ctr, New Orleans, LA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 247 PG 2 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700248 ER PT J AU Wilson, KM Cheng, JS Sanchez, A Graff, R Rodriguez, D Feldman, AS Barrisford, G Bechis, S Blute, M Stampfer, MJ Chang, SL Giovannucci, EL Albiges, LK Choueiri, TK Cho, EY Preston, MA AF Wilson, Kathryn M. Cheng, Jed-Sian Sanchez, Alejandro Graff, Rebecca Rodriguez, Dayron Feldman, Adam S. Barrisford, Glenn Bechis, Seth Blute, Michael Stampfer, Meir J. Chang, Steven L. Giovannucci, Edward L. Albiges, Laurence K. Choueiri, Toni K. Cho, Eunyoung Preston, Mark A. TI The association between obesity and incidence of total and fatal renal cell carcinoma in two prospective cohorts. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium CY FEB 26-28, 2015 CL Orlando, FL C1 Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Harvard Univ, Brigham & Womens Hosp, TH Chan Sch Publ Hlth, Sch Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dept Surg, Div Urol,Med Sch, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Channing Div Nework Med, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 SU S MA 414 PG 1 WC Oncology SC Oncology GA CL3XX UT WOS:000356886700411 ER PT J AU Callen, J Giardina, TD Singh, H Li, L Paoloni, R Georgiou, A Runciman, WB Westbrook, JI AF Callen, Joanne Giardina, Traber Davis Singh, Hardeep Li, Ling Paoloni, Richard Georgiou, Andrew Runciman, William B. Westbrook, Johanna I. TI Emergency Physicians' Views of Direct Notification of Laboratory and Radiology Results to Patients Using the Internet: A Multisite Survey SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE Internet; patient safety; electronic health records; patient empowerment; diagnostic tests; emergency care; radiology ID RANDOMIZED CONTROLLED-TRIAL; CLOSED MALPRACTICE CLAIMS; ELECTRONIC MEDICAL-RECORD; E-MAIL; DELAYED DIAGNOSES; INVITING PATIENTS; ENHANCE PATIENT; CANCER-PATIENTS; YOUNG-PATIENTS; DOCTORS NOTES AB Background: Patients are increasingly using the Internet to communicate with health care providers and access general and personal health information. Missed test results have been identified as a critical safety issue with studies showing up to 75% of tests for emergency department (ED) patients not being followed-up. One strategy that could reduce the likelihood of important results being missed is for ED patients to have direct access to their test results. This could be achieved electronically using a patient portal tied to the hospital's electronic medical record or accessed from the relevant laboratory information system. Patients have expressed interest in accessing test results directly, but there have been no reported studies on emergency physicians' opinions. Objective: The aim was to explore emergency physicians' current practices of test result notification and attitudes to direct patient notification of clinically significant abnormal and normal test results. Methods: A cross-sectional survey was self-administered by senior emergency physicians (site A: n=50; site B: n=39) at 2 large public metropolitan teaching hospitals in Australia. Outcome measures included current practices for notification of results (timing, methods, and responsibilities) and concerns with direct notification. Results: The response rate was 69% (61/89). More than half of the emergency physicians (54%, 33/61) were uncomfortable with patients receiving direct notification of abnormal test results. A similar proportion (57%, 35/61) was comfortable with direct notification of normal test results. Physicians were more likely to agree with direct notification of normal test results if they believed it would reduce their workload (OR 5.72, 95% CI 1.14-39.76). Main concerns were that patients could be anxious (85%, 52/61), confused (92%, 56/61), and lacking in the necessary expertise to interpret their results (90%, 55/61). Conclusions: Although patients' direct access to test results could serve as a safety net reducing the likelihood of abnormal results being missed, emergency physicians' concerns need further exploration: which results are suitable and the timing and method of direct release to patients. Methods of access, including secure Web-based patient portals with drill-down facilities providing test descriptions and result interpretations, or laboratories sending results directly to patients, need evaluation to ensure patient safety is not compromised and the processes fit with ED clinician and laboratory work practices and patient needs. C1 [Callen, Joanne; Li, Ling; Georgiou, Andrew; Westbrook, Johanna I.] Macquarie Univ, Australian Inst Hlth Innovat, Ctr Hlth Syst & Safety Res, Sydney, NSW 2109, Australia. [Giardina, Traber Davis; Singh, Hardeep] Baylor Coll Med, Houston VA HSR&D Ctr Innovat Qual Effectiveness &, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. [Paoloni, Richard] Concord Repatriat & Gen Hosp, Emergency Dept, Sydney, NSW, Australia. [Runciman, William B.] Univ Adelaide, Dept Anaesthesia & Intens Care, Joanna Briggs Inst, Adelaide, SA, Australia. RP Callen, J (reprint author), Macquarie Univ, Australian Inst Hlth Innovat, Ctr Hlth Syst & Safety Res, Level 6,75 Talavera Rd, Sydney, NSW 2109, Australia. EM joanne.callen@mq.edu.au OI Runciman, William (Bill)/0000-0001-8489-0693 FU Australian Research Council [DP120100297]; VA Health Services through the VA Office of Academic Affiliations; VA Health Services Research and Development Service [CRE 12-033]; VA National Center for Patient Safety; Agency for Health Care Research and Quality [R01HS022087]; Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety [CIN 13-413, 14-274] FX We would like to acknowledge the contributions of Louise Robertson, Michael Stewart, Julie Li, George Touli, and Elia Vecellio. This study is part of an Australian Research Council Discovery Project Grant (DP120100297) to investigate whether technology can make communication in complex systems safer and more efficient.; Dr Giardina is supported by the VA Health Services Research postdoctoral fellowship through the VA Office of Academic Affiliations. Dr Singh is supported by the VA Health Services Research and Development Service (CRE 12-033; Presidential Early Career Award for Scientists and Engineers USA 14-274), the VA National Center for Patient Safety and the Agency for Health Care Research and Quality (R01HS022087). This work is also supported in part by the Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413). NR 67 TC 2 Z9 2 U1 3 U2 10 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 MAR PY 2015 VL 17 IS 3 AR e60 DI 10.2196/jmir.3721 PG 13 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA CL2NJ UT WOS:000356780900003 PM 25739322 ER PT J AU Agboola, SO Ju, W Elfiky, A Kvedar, JC Jethwani, K AF Agboola, Stephen O. Ju, Woong Elfiky, Aymen Kvedar, Joseph C. Jethwani, Kamal TI The Effect of Technology-Based Interventions on Pain, Depression, and Quality of Life in Patients With Cancer: A Systematic Review of Randomized Controlled Trials SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Review DE telehealth; connected health; cancer; telephone; pain; depression; quality of life; systematic review; randomized controlled trials ID STAGE BREAST-CANCER; TELEPHONE INTERVENTION; CARE INTERVENTION; COLORECTAL-CANCER; SUPPORTIVE CARE; CLINICAL-TRIAL; OUTCOMES; SURVIVORS; PROGRAM; MANAGEMENT AB Background: The burden of cancer is increasing; projections over the next 2 decades suggest that the annual cases of cancer will rise from 14 million in 2012 to 22 million. However, cancer patients in the 21st century are living longer due to the availability of novel therapeutic regimens, which has prompted a growing focus on maintaining patients' health-related quality of life. Telehealth is increasingly being used to connect with patients outside of traditional clinical settings, and early work has shown its importance in improving quality of life and other clinical outcomes in cancer care. Objective: The aim of this study was to systematically assess the literature for the effect of supportive telehealth interventions on pain, depression, and quality of life in cancer patients via a systematic review of clinical trials. Methods: We searched PubMed, EMBASE, Google Scholar, CINAHL, and PsycINFO in July 2013 and updated the literature search again in January 2015 for prospective randomized trials evaluating the effect of telehealth interventions in cancer care with pain, depression, and quality of life as main outcomes. Two of the authors independently reviewed and extracted data from eligible randomized controlled trials, based on pre-determined selection criteria. Methodological quality of studies was assessed by the Cochrane Collaboration risk of bias tool. Results: Of the 4929 articles retrieved from databases and relevant bibliographies, a total of 20 RCTs were included in the final review. The studies were largely heterogeneous in the type and duration of the intervention as well as in outcome assessments. A majority of the studies were telephone-based interventions that remotely connected patients with their health care provider or health coach. The intervention times ranged from 1 week to 12 months. In general, most of the studies had low risk of bias across the domains of the Cochrane Collaboration risk of bias tool, but most of the studies had insufficient information about the allocation concealment domain. Two of the three studies focused on pain control reported significant effects of the intervention; four of the nine studies focus on depression reported significant effects, while only the studies that were focused on quality of life reported significant effects. Conclusions: This systematic review demonstrates the potential of telehealth interventions in improving outcomes in cancer care. However, more high-quality large-sized trials are needed to demonstrate cogent evidence of its effectiveness. C1 [Agboola, Stephen O.; Kvedar, Joseph C.; Jethwani, Kamal] Partners Healthcare Ctr Connected Hlth, Boston, MA 02114 USA. [Agboola, Stephen O.; Kvedar, Joseph C.; Jethwani, Kamal] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Agboola, Stephen O.; Elfiky, Aymen; Kvedar, Joseph C.; Jethwani, Kamal] Harvard Univ, Sch Med, Boston, MA USA. [Ju, Woong] Ewha Womans Univ, Dept Obstet & Gynecol, Coll Med, Med Res Inst, Seoul, South Korea. [Elfiky, Aymen] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Agboola, SO (reprint author), Partners Healthcare Ctr Connected Hlth, 25 New Chardon St,Suite 300, Boston, MA 02114 USA. EM sagboola@partners.org NR 41 TC 11 Z9 11 U1 4 U2 13 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 MAR PY 2015 VL 17 IS 3 AR e65 DI 10.2196/jmir.4009 PG 14 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA CL2NJ UT WOS:000356780900007 PM 25793945 ER PT J AU Bossarte, R AF Bossarte, Robert TI Enhancing Surveillance of Suicide Ideation and Suicide Attempt Through Integration of Data from Multiple Systems SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID PREVENTION; RISK C1 [Bossarte, Robert] US Dept Vet Affairs, Off Publ Hlth, Rochester, NY USA. RP Bossarte, R (reprint author), Univ Rochester, Off Publ Hlth, US Dept Vet Affairs, Dept Psychiat,Sch Med & Dent, Rochester, NY 14642 USA. EM Robert.Bossarte@va.gov NR 9 TC 0 Z9 0 U1 3 U2 4 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 370 SEVENTH AVE, SUITE 1200, NEW YORK, NY 10001-1020 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD SPR PY 2015 VL 78 IS 1 BP 22 EP 24 DI 10.1080/00332747.2015.1021657 PG 3 WC Psychiatry SC Psychiatry GA CK6DN UT WOS:000356318800002 PM 26168023 ER PT J AU Fisher, LB Overholser, JC Ridley, J Braden, A Rosoff, C AF Fisher, Lauren B. Overholser, James C. Ridley, Josephine Braden, Abby Rosoff, Cari TI From the Outside Looking In: Sense of Belonging, Depression, and Suicide Risk SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID INTERPERSONAL-PSYCHOLOGICAL THEORY; PERCEIVED SOCIAL SUPPORT; PSYCHIATRIC OUTPATIENTS; PSYCHOMETRIC PROPERTIES; MULTIDIMENSIONAL SCALE; HOPELESSNESS SCALE; CONSTRUCT-VALIDITY; MALE VETERANS; INVENTORY-II; LIFE STRESS AB Sense of belonging has demonstrated significant relationships with depression and suicidal thoughts, highlighting its potential utility in refining assessment of suicide risk. Method: Structured clinical interviews and self-report measures were used to assess depression, suicidal behaviors, hopelessness, life stress, social support, and sense of belonging in a sample of 116 depressed psychiatric patients. Results: Lower sense of belonging was significantly associated with greater severity of depression, hopelessness, suicidal ideation, and history of prior suicide attempt(s). However, sense of belonging did not predict suicidal ideation and history of prior suicide attempt(s) beyond the association between suicidal behaviors and established risk factors. Sense of belonging displayed a significant relationship with depression and hopelessness and is likely to play a critical role in both the development of and recovery from depression. Conclusions: Sense of belonging is directly related to depression and hopelessness, while indirecdy related to suicidal ideation. Low sense of belonging provides an important target for assessment and intervention in the treatment of depression. Cognitive, behavioral, and interpersonal interventions may help improve an individual's sense of belonging and decrease symptoms of depression and hopelessness. C1 [Fisher, Lauren B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Overholser, James C.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Ridley, Josephine] Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA. [Braden, Abby] Univ Calif San Diego, San Diego, CA 92103 USA. [Rosoff, Cari] Virginia Polytech Inst & State Univ, Roanoke, VA USA. RP Fisher, LB (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM lbfisher@mgh.harvard.edu NR 58 TC 4 Z9 4 U1 3 U2 8 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 370 SEVENTH AVE, SUITE 1200, NEW YORK, NY 10001-1020 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD SPR PY 2015 VL 78 IS 1 BP 29 EP 41 DI 10.1080/00332747.2015.1015867 PG 13 WC Psychiatry SC Psychiatry GA CK6DN UT WOS:000356318800004 PM 26168025 ER PT J AU Johnson, RS Stolar, AG Wu, E Coonan, LA Graham, DP AF Johnson, R. Scott Stolar, Andrea G. Wu, Emily Coonan, Loretta A. Graham, David P. TI An analysis of successful outcomes and associated contributing factors in veterans' court SO BULLETIN OF THE MENNINGER CLINIC LA English DT Article ID DRUG AB This study aims to examine the extent to which a veteran's propensity for arrest following separation from veterans' court is associated with that veteran's length of stay within the program, type of discharge, or number of judicial sanctions issued. This is a retrospective chart review that focuses on the first 100 participants in the Harris County Veterans' Court Program. After controlling for a number of demographic factors, both arrests during enrollment in the veterans' court program (p = .031) and Factor Score 1 (unsuccessful discharge, fewer months in the veterans' court program, and more months of follow up) (p = .042) were predictive of arrest following separation from the veterans' court program. In addition, a prior diagnosis of opiate misuse was also predictive of arrest following separation (p < .001). Given these findings, veterans' court judges and program administrators might examine ways of continuing enrollment for veterans at highest risk for recidivism. C1 [Johnson, R. Scott] Michael E DeBakey Vet Affairs VA Med Ctr, Mental Hlth Care Line, Houston, TX USA. [Johnson, R. Scott] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Stolar, Andrea G.; Graham, David P.] Baylor Coll Med, Psychiat, Houston, TX 77030 USA. [Wu, Emily] Baylor Coll Med, Houston, TX 77030 USA. [Coonan, Loretta A.] Michael E DeBakey Med Ctr, Houston, TX USA. [Graham, David P.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Graham, David P.] Michael E DeBakey VA Med Ctr, Neurorehabil Neurons Networks Traumat Brain Injur, Houston, TX USA. RP Johnson, RS (reprint author), 1977 Butler Blvd,Suite E4-400, Houston, TX 77030 USA. EM rscottjohnson3@gmail.com NR 5 TC 2 Z9 2 U1 0 U2 1 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 370 SEVENTH AVE, SUITE 1200, NEW YORK, NY 10001-1020 USA SN 0025-9284 EI 1943-2828 J9 B MENNINGER CLIN JI Bull. Menninger Clin. PD SPR PY 2015 VL 79 IS 2 BP 166 EP 173 PG 8 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA CJ7RD UT WOS:000355695000004 PM 26035089 ER PT J AU Schlett, CL Hoffmann, U Geisler, T Nikolaou, K Bamberg, F AF Schlett, Christopher L. Hoffmann, Udo Geisler, Tobias Nikolaou, Konstantin Bamberg, Fabian TI Cardiac Computed Tomography for the Evaluation of the Acute Chest Pain Syndrome: State of the Art SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Acute chest pain syndrome; Acute coronary syndrome; Cardiac Computed tomography; CCTA ID ACUTE CORONARY SYNDROME; NAPKIN-RING SIGN; LEFT-VENTRICULAR FUNCTION; EMERGENCY-DEPARTMENT; CT ANGIOGRAPHY; ATHEROSCLEROTIC PLAQUE; COST-EFFECTIVENESS; ROMICAT TRIAL; MYOCARDIAL-PERFUSION; PROGNOSTIC VALUE AB Coronary computed tomography angiography (CCTA) is recommended for the triage of acute chest pain in patients with a low-to-intermediate likelihood for acute coronary syndrome. Absence of coronary artery disease (CAD) confirmed by CCTA allows rapid emergency department discharge. This article shows that CCTA-based triage is as safe as traditional triage, reduces the hospital length of stay, and may provide cost-effective or even cost-saving care. C1 [Schlett, Christopher L.] Univ Heidelberg Hosp, Dept Diagnost & Intervent Radiol, D-69120 Heidelberg, Germany. [Schlett, Christopher L.; Hoffmann, Udo; Bamberg, Fabian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Geisler, Tobias] Univ Tubingen Hosp, Dept Cardiol & Cardiovasc Med, D-72076 Tubingen, Germany. [Nikolaou, Konstantin; Bamberg, Fabian] Univ Tubingen Hosp, Dept Diagnost & Intervent Radiol, D-72076 Tubingen, Germany. RP Bamberg, F (reprint author), Univ Tubingen Hosp, Dept Diagnost & Intervent Radiol, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. EM fabian.bamberg@med.uni-tuebingen.de FU Bayer Healthcare; Siemens Healthcare FX Financial Disclosures and Conflicts of Interest: Dr F. Bamberg received unrestricted research grants from Bayer Healthcare and Siemens Healthcare. He serves on the speakers' bureau of Bayer Healthcare and Siemens Healthcare. Dr K. Nikolaou has served on a scientific advisory board for Bayer Schering Pharma and on speakers' bureaus for and has received speaker honoraria from Bayer Schering Pharma, Bracco, and Siemens Medical Solutions. NR 47 TC 5 Z9 5 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 EI 1557-8275 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAR PY 2015 VL 53 IS 2 BP 297 EP + DI 10.1016/j.rcl.2014.11.007 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CJ3NA UT WOS:000355389900005 PM 25726995 ER PT J AU van Tellingen, O Yetkin-Arik, B de Gooijer, MC Wesseling, P Wurdinger, T de Vries, HE AF van Tellingen, O. Yetkin-Arik, B. de Gooijer, M. C. Wesseling, P. Wurdinger, T. de Vries, H. E. TI Overcoming the blood-brain tumor barrier for effective glioblastoma treatment SO DRUG RESISTANCE UPDATES LA English DT Review DE Glioma; Blood-brain barrier; Drug delivery ID CONVECTION-ENHANCED DELIVERY; CANCER RESISTANCE PROTEIN; RECURRENT MALIGNANT GLIOMA; PEGYLATED LIPOSOMAL DOXORUBICIN; P-GLYCOPROTEIN ABCB1; CAPILLARY ENDOTHELIAL-CELLS; CENTRAL-NERVOUS-SYSTEM; HIGH-GRADE GLIOMA; PHASE-II TRIAL; MULTIDRUG-RESISTANCE AB Gliomas are the most common primary brain tumors. Particularly in adult patients, the vast majority of gliomas belongs to the heterogeneous group of diffuse gliomas, i.e. glial tumors characterized by diffuse infiltrative growth in the preexistent brain tissue. Unfortunately, glioblastoma, the most aggressive (WHO grade IV) diffuse glioma is also by far the most frequent one. After standard treatment, the 2-year overall survival of glioblastoma patients is approximately only 25%. Advanced knowledge in the molecular pathology underlying malignant transformation has offered new handles and better treatments for several cancer types. Unfortunately, glioblastoma multiforme (GBM) patients have not yet profited as although numerous experimental drugs have been tested in clinical trials, all failed miserably. This grim prognosis for GBM is at least partly due to the lack of successful drug delivery across the blood brain tumor barrier (BBTB). The human brain comprises over 100 billion capillaries with a total length of 400 miles, a total surface area of 20 m(2) and a median inter-capillary distance of about 50 pm, making it the best perfused organ in the body. The BBTB encompasses existing and newly formed blood vessels that contribute to the delivery of nutrients and oxygen to the tumor and facilitate glioma cell migration to other parts of the brain. The high metabolic demands of high-grade glioma create hypoxic areas that trigger increased expression of VEGF and angiogenesis, leading to the formation of abnormal vessels and a dysfunctional BBTB. Even though the BBTB is considered 'leaky' in the core part of glioblastomas, in large parts of glioblastomas and, even more so, in lower grade diffuse gliomas the BBTB more closely resembles the intact blood brain barrier (BBB) and prevents efficient passage of cancer therapeutics, including small molecules and antibodies. Thus, many drugs can still be blocked from reaching the many infiltrative glioblastoma cells that demonstrate 'within-organ-metastasis' away from the core part to brain areas displaying a more organized and less leaky BBTB. Hence, drug delivery in glioblastoma deserves explicit attention as otherwise new experimental therapies will continue to fail. In the current review we highlight different aspects of the BBTB in glioma patients and preclinical models and discuss the advantages and drawbacks of drug delivery approaches for the treatment of glioma patients. We provide an overview on methods to overcome the BBTB, including osmotic blood brain barrier disruption (BBBD), bradykinin receptor-mediated BBTB opening, inhibition of multidrug efflux transporters, receptor-mediated transport systems and physiological circumvention of the BBTB. While our knowledge about the molecular biology of glioma cells is rapidly expanding and is, to some extent, already assisting us in the design of tumor-tailored therapeutics, we are still struggling to develop modalities to expose the entire tumor to such-therapeutics at pharmacologically meaningful quantities. Therefore, we must expand our knowledge about the fundamentals of the BBTB as a step toward the design of practical and safe devices and approaches for enhanced drug delivery into the diseased brain area. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Wurdinger, T.] Vrije Univ Amsterdam Med Ctr, Neurooncol Res Grp, Dept Neurosurg, Canc Ctr Amsterdam, NL-1081 BT Amsterdam, Netherlands. [Wurdinger, T.] Harvard Univ, Sch Med, Dept Neurol, Mol Neurogenet Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Yetkin-Arik, B.; de Vries, H. E.] Vrije Univ Amsterdam Med Ctr, Dept Mol Cell Biol & Immunol, NL-1081 BT Amsterdam, Netherlands. [van Tellingen, O.; de Gooijer, M. C.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Clin Chem Preclin Pharmacol, Amsterdam, Netherlands. [Wesseling, P.] Vrije Univ Amsterdam Med Ctr, Dept Pathol, NL-1081 BT Amsterdam, Netherlands. [Wesseling, P.] Radboud Univ Nijmegen Med Ctr, Dept Pathol, Nijmegen, Netherlands. RP de Vries, HE (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Mol Cell Biol & Immunol, Van der Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. EM o.v.tellingen@nki.nl; he.devries@vumc.nl RI Wesseling, P./H-8114-2014 OI Wesseling, P./0000-0001-5453-5201 FU VIDI fellowship from Dutch Organization of Scientific Research (NWO) [91711366]; European Research Council Starting Researchers Grant [336540]; Stichting Stophersentumoren.n1 FX This work was supported by the VIDI fellowship 91711366 (T.W.) from the Dutch Organization of Scientific Research (NWO), European Research Council Starting Researchers Grant 336540 (T.W), and Stichting Stophersentumoren.n1 (T.W., O.v.T.). NR 159 TC 51 Z9 52 U1 34 U2 95 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1368-7646 EI 1532-2084 J9 DRUG RESIST UPDATE JI Drug Resist. Update PD MAR PY 2015 VL 19 BP 1 EP 12 DI 10.1016/j.drup.2015.02.002 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CI8ME UT WOS:000355025600001 PM 25791797 ER PT J AU Shapero, K Wylie-Sears, J Levine, RA Mayer, JE Bischoff, J AF Shapero, Kayle Wylie-Sears, Jill Levine, Robert A. Mayer, John E., Jr. Bischoff, Joyce TI Reciprocal interactions between mitral valve endothelial and interstitial cells reduce endothelial-to-mesenchymal transition and myofibroblastic activation SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE Mitral valve; Endothelial cells; Endothelial-to-mesenchymal transition; Valve interstitial cells ID GROWTH-FACTOR-BETA; PROGENITOR CELLS; TGF-BETA; EXTRACELLULAR-MATRIX; DEPENDENT REGULATION; SUBSTRATE STIFFNESS; CARDIAC VALVES; HEART-FAILURE; DISEASE; MECHANISMS AB Thickening of mitral leaflets, endothelial-to-mesenchymal transition (EndMT), and activated myofibroblast-like interstitial cells have been observed in ischemic mitral valve regurgitation. We set out to determine if interactions between mitral valve endothelial cells (VECs) and interstitial cells (VICs) might affect these alterations. We used in vitro co-culture in Transwell (TM) inserts to test the hypothesis that VICs secrete factors that inhibit EndMT and conversely, that VECs secrete factors that mitigate the activation of VICs to a myofibroblast-like, activated phenotype. Primary cultures and clonal populations of ovine mitral VICs and VECs were used. Western blot, quantitative reverse transcriptase PCR (qPCR) and functional assays were used to assess changes in cell phenotype and behavior. VICs or conditioned media from VICs inhibited transforming growth factor beta (TGF beta)-induced EndMT in VECs, as indicated by reduced expression of EndMT markers alpha-smooth muscle actin (alpha-SMA), Slug, Snail and MMP-2 and maintained the ability of VECs to mediate leukocyte adhesion, an important endothelial function. VECs or conditioned media from VECs reversed the spontaneous cell culture-induced change in VICs to an activated phenotype, as indicated by reduced expression of alpha-SMA and type I collagen, increased expression chondromodulin-1 (Chm1), and reduced contractile activity. These results demonstrate that mitral VECs and VICs secrete soluble factors that can reduce VIC activation and inhibit TCF beta-driven EndMT, respectively. These findings suggest that the endothelium of the mitral valve is critical for the maintenance of a quiescent VIC phenotype and that, in turn, VICs prevent EndMT. We speculate that the disturbance of the ongoing reciprocal interactions between VECs and VICs in vivo may contribute to the thickened and fibrotic leaflets observed in ischemic mitral regurgitation, and in other types of valve disease. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Shapero, Kayle; Wylie-Sears, Jill; Bischoff, Joyce] Harvard Univ, Sch Med, Boston Childrens Hosp, Vasc Biol Program,Dept Surg, Boston, MA 02115 USA. [Shapero, Kayle] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Shapero, Kayle; Mayer, John E., Jr.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Cardiothorac Surg, Cambridge, MA 02138 USA. [Levine, Robert A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Bischoff, J (reprint author), Boston Childrens Hosp, Vasc Biol Program, Karp Family Res Bldg 12 212, Boston, MA 02115 USA. EM joyce.bischoff@childrens.harvard.edu OI Bischoff, Joyce/0000-0002-6367-1974 FU NHLBI of the National Institutes of Health [R01HL109506-01A1]; Fondation Leducq Transatlantic Network; Tommy Kaplan Discretionary Fund FX Research reported in this manuscript was supported by the NHLBI of the National Institutes of Health under award number R01HL109506-01A1, to R.A.L and J.B. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The study was also supported by the Fondation Leducq Transatlantic Network (R.A.L and J.B.) and the Tommy Kaplan Discretionary Fund (J.E.M.) NR 57 TC 10 Z9 11 U1 1 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAR PY 2015 VL 80 BP 175 EP 185 DI 10.1016/j.yjmcc.2015.01.006 PG 11 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA CJ3MZ UT WOS:000355389800020 PM 25633835 ER PT J AU Ducharme, S Dickerson, BC Larvie, M Price, BH AF Ducharme, Simon Dickerson, Bradford C. Larvie, Mykol Price, Bruce H. TI Differentiating Frontotemporal Dementia From Catatonia: A Complex Neuropsychiatric Challenge SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Letter ID AKINETIC CATATONIA; CORTICAL DYSFUNCTION C1 [Ducharme, Simon; Price, Bruce H.] McLean Hosp, Dept Neurol, Behav Neurol & Neuropsychiat Clin, Belmont, MA 02178 USA. [Ducharme, Simon] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ducharme, Simon; Dickerson, Bradford C.; Price, Bruce H.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Larvie, Mykol] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ducharme, Simon] McGill Univ, Dept Psychiat, Ctr Hlth, Montreal, PQ, Canada. [Ducharme, Simon] McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ, Canada. RP Ducharme, S (reprint author), McLean Hosp, Dept Neurol, Behav Neurol & Neuropsychiat Clin, Belmont, MA 02178 USA. EM simon.ducharme@mcgill.ca NR 10 TC 2 Z9 2 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 EI 1545-7222 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 2015 VL 27 IS 2 BP E174 EP E176 DI 10.1176/appi.neuropsych.14070157 PG 3 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ1NM UT WOS:000355250300027 PM 25923875 ER PT J AU Ducharme, S Dickerson, BC Price, BH AF Ducharme, Simon Dickerson, Bradford C. Price, Bruce H. TI Improvement in Athletic Performance as an Early Symptom of Behavioral Variant Frontotemporal Dementia SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Letter ID EXPERIENCE; SAMPLE; CORTEX; FLOW C1 [Ducharme, Simon; Price, Bruce H.] McLean Hosp, Dept Neurol, Behav Neurol & Neuropsychiat Clin, Belmont, MA 02178 USA. [Ducharme, Simon] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ducharme, Simon; Dickerson, Bradford C.; Price, Bruce H.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ducharme, Simon] McGill Univ, Dept Psychiat, Ctr Hlth, Montreal, PQ, Canada. [Ducharme, Simon] McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ, Canada. RP Ducharme, S (reprint author), McLean Hosp, Dept Neurol, Behav Neurol & Neuropsychiat Clin, Belmont, MA 02178 USA. EM simon.ducharme@mcgill.ca NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 EI 1545-7222 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 2015 VL 27 IS 2 BP E163 EP E164 DI 10.1176/appi.neuropsych.14060136 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ1NM UT WOS:000355250300022 PM 25923870 ER PT J AU Garza-Mayers, AC Miller, KA Russo, BC Nagda, DV Goldberg, MB AF Garza-Mayers, Anna Cristina Miller, Kelly A. Russo, Brian C. Nagda, Dipal V. Goldberg, Marcia B. TI Shigella flexneri Regulation of ARF6 Activation during Bacterial Entry via an IpgD-Mediated Positive Feedback Loop SO MBIO LA English DT Article ID NUCLEOTIDE EXCHANGE FACTOR; RIBOSYLATION FACTOR 6; PLECKSTRIN HOMOLOGY DOMAINS; III SECRETION; DOWNSTREAM ACTIVATION; EPITHELIAL-CELLS; PLASMA-MEMBRANE; PH DOMAIN; T-CELL; INVASION AB Entry into cells is critical for virulence of the human bacterial pathogens Shigella spp. Shigella spp. induce membrane ruffle formation and macropinocytic uptake, but the events instigating this process are incompletely understood. The host small GTPase ADP-ribosylation factor 6 (ARF6) functions in membrane trafficking at the plasma membrane and activates membrane ruffle formation. We demonstrate that ARF6 is required for efficient Shigella flexneri entry, is activated by S. flexneri dependent on the phosphatase activity of the type III secreted effector IpgD, and depends on cytohesin guanine nucleotide exchange factors (GEFs) for recruitment to entry sites. The cytohesin GEF ARF nucleotide binding site opener (ARNO) is recruited to these sites, also dependent on IpgD phosphatase activity. ARNO recruitment is independent of ARF6, indicating that, in addition to the described recruitment of ARNO by ARF6, ARNO is recruited upstream of ARF6. Our data provide evidence that ARF6, IpgD, phosphoinositide species, and ARNO constitute a previously undescribed positive feedback loop that amplifies ARF6 activation at bacterial entry sites, thereby promoting efficient S. flexneri uptake. IMPORTANCE Shigella spp. cause diarrhea and dysentery by infection of epithelial cells in the human colon. Critical to disease is the ability of Shigella to enter into cells, yet the mechanisms involved in entry are incompletely understood. We demonstrate that the small GTPase ADP-ribosylation factor 6 (ARF6) is required for efficient cellular entry of Shigella flexneri and that activation of ARF6 depends on the phosphatase activity of the Shigella protein IpgD, which is introduced into cells via the bacterial type III secretion system. We further show that IpgD phosphatase activity is required for recruitment of the ARF6 guanine nucleotide exchange factor (GEF) ARF nucleotide binding site opener (ARNO) to bacterial entry sites and that ARNO lies upstream of ARF6 activation. These relationships define a positive feedback loop that contributes to activation of ARF6 at S. flexneri entry sites and leads to local amplification of signals that promote bacterial entry. C1 [Garza-Mayers, Anna Cristina; Goldberg, Marcia B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Miller, Kelly A.; Russo, Brian C.; Nagda, Dipal V.; Goldberg, Marcia B.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Cambridge, MA USA. RP Goldberg, MB (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. EM marcia.goldberg@mgh.harvard.edu FU Public Health Service grant from the National Institutes of Health [R01AI081724, T32GM007753, T32AI007061] FX This work was supported by Public Health Service grant R01AI081724 (to M.B.G.), trainee support on T32GM007753 (to A.C.G.-M.), and T32AI007061 (to K.A.M. and B.C.R.) from the National Institutes of Health. NR 72 TC 5 Z9 5 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD MAR-APR PY 2015 VL 6 IS 2 AR e02584-14 DI 10.1128/mBio.02584-14 PG 12 WC Microbiology SC Microbiology GA CJ2KE UT WOS:000355312400029 PM 25736891 ER PT J AU Mitchell, AM Stone, AEL Cheng, LL Ballinger, K Edwards, MG Stoddard, M Li, H Golden-Mason, L Shaw, GM Khetani, S Rosen, HR AF Mitchell, Angela M. Stone, Amy E. L. Cheng, Linling Ballinger, Kimberly Edwards, Michael G. Stoddard, Mark Li, Hui Golden-Mason, Lucy Shaw, George M. Khetani, Salman Rosen, Hugo R. TI Transmitted/Founder Hepatitis C Viruses Induce Cell-Type- and Genotype-Specific Differences in Innate Signaling within the Liver SO MBIO LA English DT Article ID PLASMACYTOID DENDRITIC CELLS; INFECTION; INTERFERON; CANCER; HCV; IDENTIFICATION; REPLICATION; STEATOSIS; CLEARANCE; FIBROSIS AB Hepatitis C virus (HCV) infection leads to persistence in the majority of cases despite triggering complex innate immune responses within the liver. Although hepatocytes are the preferred site for HCV replication, nonparenchymal cells (NPCs) can also contribute to antiviral immunity. Recent innovations involving single-genome amplification (SGA), direct amplicon sequencing, and phylogenetic inference have identified full-length transmitted/founder (T/F) viruses. Here, we tested the effect of HCV T/F viral RNA (vRNA) on innate immune signaling within hepatocytes and NPCs, including the HepG2 and Huh 7.5.1 cell lines, a human liver endothelial cell line (TMNK-1), a plasmacytoid dendritic cell line (GEN2.2), and a monocytic cell line (THP-1). Transfection with hepatitis C T/F vRNA induced robust transcriptional upregulation of type I and III interferons (IFNs) within HepG2 and TMNK-1 cells. Both the THP-1 and GEN2.2 lines demonstrated higher type I and III IFN transcription with genotype 3a compared to genotype 1a or 1b. Supernatants from HCV T/F vRNA-transfected TMNK-1 cells demonstrated superior viral control. Primary human hepatocytes (PHH) transfected with genotype 3a induced canonical pathways that included chemokine and IFN genes, as well as overrepresentation of RIG-I (DDX58), STAT1, and a Toll-like receptor 3 (TLR3) network. Full-length molecular clones of HCV induce broad IFN responses within hepatocytes and NPCs, highlighting that signals imparted by the various cell types within the liver may lead to divergent outcomes of infection. In particular, the finding that HCV genotypes differentially induce antiviral responses in NPCs and PHH might account for relevant clinical-epidemiological observations (higher clearance but greater necroinflammation in persistence with genotype 3). IMPORTANCE Hepatitis C virus (HCV) has become a major worldwide problem, and it is now the most common viral infection for which there is no vaccine. HCV infection often leads to persistence of the virus and is a leading cause of chronic hepatitis, liver cancer, and cirrhosis. There are multiple genotypes of the virus, and patients infected with different viral genotypes respond to traditional therapy differently. However, the immune response to the virus within the liver has not been fully elucidated. Here, we determined the responses to different genotypes of HCV in cell types of the liver. We found that the immune response varied according to both cell type and HCV genotype, leading to a more pronounced induction of inflammatory pathways after exposure to certain genotypes. Therefore, inflammatory pathways that are being robustly activated by certain HCV genotypes could lead to more severe damage to the liver, inducing diverse outcomes and responses to therapy. C1 [Mitchell, Angela M.; Stone, Amy E. L.; Golden-Mason, Lucy; Rosen, Hugo R.] Univ Colorado Denver, Integrated Dept Immunol, Denver, CO 80204 USA. [Mitchell, Angela M.; Stone, Amy E. L.; Golden-Mason, Lucy; Rosen, Hugo R.] Natl Jewish Hlth, Denver, CO USA. [Mitchell, Angela M.; Stone, Amy E. L.; Cheng, Linling; Golden-Mason, Lucy; Rosen, Hugo R.] Univ Colorado Denver, Div Gastroenterol & Hepatol, Hepatitis Ctr C, Dept Med, Denver, CO USA. [Ballinger, Kimberly; Khetani, Salman] Colorado State Univ, Mech & Biomed Engn, Ft Collins, CO 80523 USA. [Edwards, Michael G.] Univ Colorado Denver, Dept Med, Div Pulm Sci & Crit Care Med, Aurora, CO USA. [Stoddard, Mark; Li, Hui; Shaw, George M.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Rosen, Hugo R.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Rosen, HR (reprint author), Univ Colorado Denver, Integrated Dept Immunol, Denver, CO 80204 USA. EM hugo.rosen@ucdenver.edu FU National Institutes of Health [R21 AI 103361, R21-AI 106000]; HCV Center [U19 AI 1066328]; VA Merit Review grant (Department of Veteran's Affairs) FX This work was supported by R21 AI 103361 (National Institutes of Health), U19 AI 1066328 (HCV Center grant), and a VA Merit Review grant (Department of Veteran's Affairs) to H.R.R. and R21-AI 106000 (National Institutes of Health) to G.M.S. NR 46 TC 3 Z9 3 U1 2 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD MAR-APR PY 2015 VL 6 IS 2 AR e02510-14 DI 10.1128/mBio.02510-14 PG 11 WC Microbiology SC Microbiology GA CJ2KE UT WOS:000355312400065 PM 25714713 ER PT J AU de Moya, MA Sideris, AC Choy, G Chang, YC Landman, WB Cropano, CM Cohn, SM AF de Moya, Marc A. Sideris, Antonios C. Choy, Garry Chang, Yuchiao Landman, Wendy B. Cropano, Catrina M. Cohn, Stephen M. TI Appendectomy and Pregnancy: Gestational Age Does Not Affect the Position of the Incision SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT 7th Annual Academic Surgical Congress of the Association-for-Academic-Surgery CY FEB 14-16, 2012 CL Las Vegas, NV SP Assoc Acad Surg ID LOWER-QUADRANT PAIN; SUSPECTED APPENDICITIS; PELVIC PAIN; MRI; PATIENT; WOMEN; LOCATION; RISK AB The position of the base of the appendix during advancing gestational age is based on inadequate data. Therefore, the proper location for an appendectomy incision during pregnancy is highly unclear. This study investigated the location of the appendix during pregnancy to determine the optimal location for an incision in pregnant patients with appendicitis relative to McBurney's point. Magnetic resonance images (MRIs) were reviewed independently by two fellowship-trained abdominal MRI radiologists blinded to the imaging report. The distance of the appendix from anatomic landmarks was measured in a total of 114 pregnant women with an abdominal or pelvic MRI who were admitted between 2001 and 2011 at a Level I trauma center. Patients with a history of appendectomy were excluded. The distance from the base of the appendix to McBurney's point changed over the course of the gestation by only 1.2 cm and which did not amount to a clinically or statistically significant change in position. Our data provide evidence that there is minimal upward or lateral displacement of the appendix during pregnancy, and therefore its distance from the McBurney's point remains essentially unchanged. These findings justify the use of the McBurney's incision for appendectomy during pregnancy regardless of the trimester. C1 [de Moya, Marc A.; Sideris, Antonios C.; Cropano, Catrina M.] Massachusetts Gen Hosp, Dept Surg, Div Trauma, Boston, MA 02114 USA. [Choy, Garry] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Landman, Wendy B.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Cohn, Stephen M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX 78229 USA. RP de Moya, MA (reprint author), Massachusetts Gen Hosp, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM mdemoya@partners.org NR 29 TC 1 Z9 1 U1 1 U2 1 PU SOUTHEASTERN SURGICAL CONGRESS PI CUMMING PA 115 SAMARITAN DR, #200, CUMMING, GA 30040-2354 USA SN 0003-1348 EI 1555-9823 J9 AM SURGEON JI Am. Surg. PD MAR PY 2015 VL 81 IS 3 BP 282 EP 288 PG 7 WC Surgery SC Surgery GA CI6TN UT WOS:000354895100031 PM 25760205 ER PT J AU Bardia, A AF Bardia, A. TI TARGETING THE ESTROGEN RECEPTOR: OLD RECEPTOR, NEW DRUG(S) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 13th International Congress on Targeted Anticancer Therapies (TAT) CY MAR 02-04, 2015 CL Paris, FRANCE ID BREAST-CANCER; MUTATIONS C1 [Bardia, A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 4 TC 1 Z9 1 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 MAR PY 2015 VL 26 SU 2 MA O3.1 BP 3 EP 3 DI 10.1093/annonc/mdv081.1 PG 1 WC Oncology SC Oncology GA CI4OC UT WOS:000354729300004 ER PT J AU Gainor, J AF Gainor, J. TI Next generation ALK inhibitors and mechanisms of resistance to therapy SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 13th International Congress on Targeted Anticancer Therapies (TAT) CY MAR 02-04, 2015 CL Paris, FRANCE C1 [Gainor, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 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 MAR PY 2015 VL 26 SU 2 MA O10.1 BP 14 EP 14 DI 10.1093/annonc/mdv088.1 PG 1 WC Oncology SC Oncology GA CI4OC UT WOS:000354729300012 ER PT J AU Sher, L AF Sher, Leo TI Suicide in Men SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID OF-THE-LITERATURE; TESTOSTERONE LEVELS; BIPOLAR DISORDER; BEHAVIOR; LITHIUM; GENDER; IMPULSIVITY C1 [Sher, Leo] James J Peters Vet Adm Med Ctr, New York, NY 10468 USA. [Sher, Leo] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, 130 West Kingsbridge Rd, New York, NY 10468 USA. EM Leo.Sher@mssm.edu NR 21 TC 3 Z9 3 U1 2 U2 11 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 MAR PY 2015 VL 76 IS 3 BP E371 EP E372 DI 10.4088/JCP.14com09554 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CI7PD UT WOS:000354955400008 PM 25830461 ER PT J AU Brennan, MB Barocas, JA Crnich, CJ Hess, TM Kolehmainen, CJ Sosman, JM Sethi, AK AF Brennan, Meghan B. Barocas, Joshua A. Crnich, Christopher J. Hess, Timothy M. Kolehmainen, Christine J. Sosman, James M. Sethi, Ajay K. TI "Oops! I forgot HIV": Resident physician self-audits and universal HIV screening SO JOURNAL OF INFECTION AND PUBLIC HEALTH LA English DT Article DE HIV screening; Self-audit feedback; Chart review; Medical resident education; Qualitative ID HEALTH-CARE SETTINGS; UNITED-STATES; ANTIRETROVIRAL THERAPY; RECOMMENDATIONS; PREVENTION; RISK; PREVALENCE; BEHAVIORS; VETERANS; ADULTS AB Background: Innovations are needed to increase universal HIV screening by primary care providers. One potential intervention is self-audit feedback, which describes the process of a clinician reviewing their own patient charts and reflecting on their performance. Methods: The effectiveness of self-audit feedback was investigated using a mixed methods approach. A total of 2111 patient charts were analyzed in a quantitative pre-post intervention study design, where the intervention was providing self-audit feedback to all internal medicine residents at one institution through an annual chart review. Qualitative data generated from the subsequent resident focus group discussions explored the motivation and mechanism for change using a knowledge attitude behavior framework. Results: The proportion of primary care patients screened for HIV increased from 17.9% (190/1060) to 40.3% (423/1051). The adjusted odds ratio of a patient being screened following resident self-audited feedback was 3.17 (95% Cl 2.11, 4.76, p < 0.001). Focus group participants attributed the improved performance to the self-audit feedback. Conclusions: Self-audit feedback is a potentially effective intervention for increasing universal HIV screening in primary care. This strategy may be most useful in settings where (1) baseline performance is low, (2) behavioral change is provider-driven, and (3) resident trainees are targeted. Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University for Health Sciences. C1 [Brennan, Meghan B.; Barocas, Joshua A.; Crnich, Christopher J.; Hess, Timothy M.; Kolehmainen, Christine J.; Sosman, James M.] Univ Wisconsin, Dept Med, Madison, WI 53705 USA. [Brennan, Meghan B.; Crnich, Christopher J.; Sethi, Ajay K.] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53726 USA. [Brennan, Meghan B.; Crnich, Christopher J.; Hess, Timothy M.; Kolehmainen, Christine J.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Brennan, MB (reprint author), UWMF Centennial Bldg,5th Floor,1685 Highland Ave, Madison, WI 53705 USA. EM mbbrennan@medicine.wisc.edu; jbarocas@medicine.wisc.edu; cjc@medicine.wisc.edu; tmhess@medicine.wisc.edu; Christine.Kolehmainen@va.gov; jms@medicine.wisc.edu; aksethi@wisc.edu OI Crnich, Christopher/0000-0002-9320-9262 FU University of Wisconsin Department of Medicine; University of Wisconsin Department of Population Health Sciences; VA Advanced Women's Health Research Fellowship FX This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. However, the authors did receive general support from the University of Wisconsin Departments of Medicine and Population Health Sciences and the VA Advanced Women's Health Research Fellowship. These sources did not have a role in study design; collection, analysis and interpretation of data; writing; or the decision to submit the article for publication. This is GRECC manuscript 2014-022. NR 34 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1876-0341 EI 1876-035X J9 J INFECT PUBLIC HEAL JI J. Infect. Public Health PD MAR-APR PY 2015 VL 8 IS 2 BP 161 EP 169 DI 10.1016/j.jiph.2014.08.010 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA CI7SK UT WOS:000354964700007 PM 25277258 ER PT J AU Nau, P Molina, G Shima, A Hani, A Meireles, O AF Nau, Peter Molina, George Shima, Aran Hani, Abujudeh Meireles, Ozanan TI Roux-en-Y gastric bypass is associated with an increased exposure to ionizing radiation SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Article DE Roux-en-Y gastric bypass; Ionizing radiation; Weight loss surgery; Radiation exposure ID LAPAROSCOPIC BARIATRIC SURGERY; SWEDISH OBESE SUBJECTS; INTERNAL HERNIAS; COMPUTED-TOMOGRAPHY; BODY-MASS; RISK; MORTALITY; WEIGHT; CANCER; CT AB Background: Bariatric surgery provides for a reliable and sustainable solution to the obesity epidemic. The gold standard bariatric surgical procedure is the Roux-en-Y gastric bypass (RYGB). Assessment of this population preoperatively and work-up of postoperative complications often includes radiographic evaluation. Repeated exposure to radiation is not without complication. Objective: Assess the association between the RYGB and exposure to ionizing radiation. Setting: Academic medical center. Methods: Patients were identified by their ICD-9 code as having had a RYGB at the Massachusetts General Hospital (MGH) from 2002 to 2012. The number of abdominal and pelvis (A/P) computed tomography (CT) scans performed was determined and converted into an effective dose (ED) and expressed as milliSeiverts (mSv) to illustrate the biologic effects of radiation. Results: From 2002 to 2012, 1789 primary laparoscopic RYGBs were completed. Fifty-five revisional operations were completed on 51 patients. Of these, 38 had both their index and second operation at the MGH. A total of 1065 A/P CTs were completed in the laparoscopic RYGB population (mean = .6), and 106 A/P CTs were done in the revisional surgery cohort (mean = 2.8). The mean ED of radiation was 56.1 mSv and 19.5 mSv for the index and revisional populations, respectively. Conclusions: This study demonstrated the significant cumulative radiation exposure attributable to A/P CTs. This exposes the patient to a potential increased risk of malignancy as well as imposing a financial burden on the healthcare system. The findings of this study raise the awareness of an increased risk of radiation exposure for this population and the necessity of creation of a dedicated algorithm for the mindful utilization of CT imaging. (C) 2015 American Society for Metabolic and Bariatric Surgery. All rights reserved. C1 [Nau, Peter] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [Molina, George; Shima, Aran; Hani, Abujudeh; Meireles, Ozanan] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Nau, P (reprint author), 200 Hawkins Dr, Iowa City, IA 52242 USA. EM peter-nau@uiowa.edu NR 37 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-7289 EI 1878-7533 J9 SURG OBES RELAT DIS JI Surg. Obes. Relat. Dis. PD MAR-APR PY 2015 VL 11 IS 2 BP 308 EP 312 DI 10.1016/j.soard.2014.07.022 PG 5 WC Surgery SC Surgery GA CI0HU UT WOS:000354418500011 PM 25820075 ER PT J AU Hurtado, DA Nelson, CC Hashimoto, D Sorensen, G AF Hurtado, David A. Nelson, Candace C. Hashimoto, Dean Sorensen, Glorian TI Supervisors' Support for Nurses' Meal Breaks and Mental Health SO WORKPLACE HEALTH & SAFETY LA English DT Article DE supervisor support; meal breaks; mental health; hospital nurses ID WORK-FAMILY CONFLICT; PATIENT-CARE WORKERS; REST BREAKS; MUSCULOSKELETAL DISORDERS; STRESS; IMPACT; RISK; PERSPECTIVE; SCHEDULES AB Meal breaks promote occupational health and safety; however, less is known about supervisors' support for nurses' meal breaks. In this study, the researchers tested whether the frequency of meal breaks was positively related to supervisors' support of nurses' meal breaks, and whether more frequent meal breaks were associated with less psychological distress. This study is based on a cross-sectional survey of 1,595 hospital nurses working on 85 units supervised by nursing directors. Specific meal-break support was measured at the nursing director level; frequency of meal breaks and psychological distress were measured at the individual nurse level. Multilevel adjusted models showed a positive association between supervisors' support for meal breaks and the frequency of nurses' meal breaks ( = .16, p < .001). Moreover, nurses who took meal breaks more frequently reported lower psychological distress ( = -.09, p < .05). Meal breaks might be daily opportunities to promote mental health and fatigue recovery and provide downtime. C1 [Hurtado, David A.] Harvard Univ, TH Chan Sch Publ Hlth, Ctr Work Hlth & Well Being, Boston, MA 02115 USA. [Nelson, Candace C.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Sorensen, Glorian] Harvard Univ, TH Chan Sch Publ Hlth, Social & Behav Sci, Boston, MA 02115 USA. [Hashimoto, Dean] Partners HealthCare Syst, Occupat Hlth Serv, Occupat & Environm Med, Boston, MA USA. [Sorensen, Glorian] Dana Farber Canc Inst, Fac Dev, Boston, MA USA. RP Hurtado, DA (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, 677 Huntington Ave,Kresge Bldg 7th Floor, Boston, MA 02115 USA. EM dhurtado@mail.harvard.edu FU National Institute for Occupational Safety and Health [U19 OH008861] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by a grant from the National Institute for Occupational Safety and Health (U19 OH008861) for the Harvard School of Public Health Center for Work, Health, and Well-Being. NR 34 TC 3 Z9 3 U1 0 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2165-0799 EI 2165-0969 J9 WORKPLACE HEALTH SAF JI Workplace Health Saf. PD MAR PY 2015 VL 63 IS 3 BP 107 EP 115 DI 10.1177/2165079915571354 PG 9 WC Nursing SC Nursing GA CI8AT UT WOS:000354990500003 PM 25994975 ER PT J AU Chambers, KJ Lehmann, AE Remenschneider, A Dedmon, M Meier, J Gray, ST Lin, DT AF Chambers, Kyle J. Lehmann, Ashton E. Remenschneider, Aaron Dedmon, Matthew Meier, Josh Gray, Stacey T. Lin, Derrick T. TI Incidence and Survival Patterns of Sinonasal Undifferentiated Carcinoma in the United States SO JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE LA English DT Article DE sinonasal undifferentiated carcinoma; SNUC; survival; multimodal treatment; neuroendocrine tumors ID OLFACTORY NEUROBLASTOMA; AGGRESSIVE NEOPLASM; EXPERIENCE; DIFFERENTIATION; MALIGNANCIES; FAILURE; NECK; HEAD AB Objective To determine trends in sinonasal undifferentiated carcinoma (SNUC) survival patterns in the United States. Design Retrospective review of national database. Participants All cases of SNUC in the National Cancer Institute's Surveillance Epidemiology and End Results program from 1973 to 2010 were examined. Main Outcome Measures Age-adjusted incidence and survival rates were calculated and stratified by demographic information and treatment modality. Cohort analysis was performed to analyze survival patterns over time. Results A total of 318 SNUC cases were identified. Age-adjusted incidence rate (IR) was 0.02 per 100,000. Incidence was greater in males (IR: 0.03) than females (IR: 0.01; p = 0.03). Overall 5- and 10-year relative survival rate was 34.9% and 31.3%, respectively. Overall median survival was 22.1 months. Median survival following surgery combined with radiation was 41.9 months. Five-year relative survival rate following surgery, radiation, or surgery combined with radiation was 38.7%, 36.0%, and 39.1%, respectively. Median survival from 1973-1986 and 1987-2010 was 14.5 and 23.5 months, respectively. Conclusions This study provides new data regarding survival patterns of SNUC in the United States, confirming survival benefit with surgery and radiation as well as identifying a trend toward improved survival in recent decades. C1 [Chambers, Kyle J.; Remenschneider, Aaron; Dedmon, Matthew; Meier, Josh; Gray, Stacey T.; Lin, Derrick T.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Chambers, Kyle J.; Lehmann, Ashton E.; Remenschneider, Aaron; Dedmon, Matthew; Meier, Josh; Gray, Stacey T.; Lin, Derrick T.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Chambers, KJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM kyle_chambers@meei.harvard.edu NR 27 TC 10 Z9 10 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 2193-6331 EI 2193-634X J9 J NEUROL SURG PART B JI Journal of Neurol. Surg. Part B PD MAR PY 2015 VL 76 IS 2 BP 94 EP 100 DI 10.1055/s-0034-1390016 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CI2XY UT WOS:000354612700003 PM 25844294 ER PT J AU Pietrzak, RH Lim, YY Ames, D Harrington, K Restrepo, C Martins, RN Rembach, A Laws, SM Masters, CL Villemagne, VL Rowe, CC Maruff, P AF Pietrzak, Robert H. Lim, Yen Ying Ames, David Harrington, Karra Restrepo, Carolina Martins, Ralph N. Rembach, Alan Laws, Simon M. Masters, Colin L. Villemagne, Victor L. Rowe, Christopher C. Maruff, Paul CA Australian Imaging Biomarkers Life TI Trajectories of memory decline in preclinical Alzheimer's disease: results from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; Memory; Trajectories; A beta; APOE ID HEALTHY OLDER-ADULTS; MILD COGNITIVE IMPAIRMENT; AMYLOID-BETA; PROSPECTIVE COHORT; EPISODIC MEMORY; DEMENTIA; ASSOCIATION; AGE; DEPOSITION; ANXIETY AB Memory changes in preclinical Alzheimer's disease (AD) are often characterized by heterogenous trajectories. However, data regarding the nature and determinants of predominant trajectories of memory changes in preclinical AD are lacking. We analyzed data from 333 cognitively healthy older adults who participated in a multicenter prospective cohort study with baseline and 18-, 36-, and 54-month follow-up assessments. Latent growth mixture modeling revealed 3 predominant trajectories of memory change: a below average, subtly declining memory trajectory (30.9%); a below average, rapidly declining memory trajectory (3.6%); and an above average, stable memory trajectory (65.5%). Compared with the stable memory trajectory, high A beta (relative risk ratio [RRR] = 2.1), and lower Mini-Mental State Examination (RRR = 0.6) and full-scale IQ (RRR =0.9) scores were independently associated with the subtly declining memory trajectory; and high Ab (RRR = 8 .3), APOE epsilon 4 carriage (RRR = 6.1), and greater subjective memory impairment (RRR - 1.2) were independently associated with the rapidly declining memory trajectory. Compared with the subtly declining memory trajectory group, APOE epsilon 4 carriage (RRR = 8.4), and subjective memory complaints (RRR = 1.2) were associated with a rapidly declining memory trajectory. These results suggest that the preclinical phase of AD may be characterized by 2 predominant trajectories of memory decline that have common (e.g., high A beta) and unique (e.g., APOE epsilon 4 genotype) determinants. Published by Elsevier Inc. C1 [Pietrzak, Robert H.] US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, Clin Neurosci Div, VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. [Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Lim, Yen Ying; Harrington, Karra; Restrepo, Carolina; Rembach, Alan; Masters, Colin L.; Villemagne, Victor L.; Maruff, Paul] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3052, Australia. [Lim, Yen Ying] Brown Univ, Warren Alpert Sch Med, Dept Neurol, Providence, RI 02912 USA. [Ames, David] Univ Melbourne, Dept Psychiat, St Vincents Hlth, Acad Unit Psychiat Old Age, Kew, Vic, Australia. [Ames, David] Natl Ageing Res Inst, Parkville, Vic, Australia. [Martins, Ralph N.; Laws, Simon M.] Edith Cowan Univ, Sch Exercise Biomed & Hlth Sci, Ctr Excellence Alzheimers Dis Res & Care, Perth, WA, Australia. [Martins, Ralph N.; Laws, Simon M.] Hollywood Private Hosp, Sir James McCusker Alzheimers Dis Res Unit, Nedlands, WA, Australia. [Villemagne, Victor L.; Rowe, Christopher C.] Austin Hlth, Dept Nucl Med, Heidelberg, Vic, Australia. [Villemagne, Victor L.; Rowe, Christopher C.] Austin Hlth, Ctr PET, Heidelberg, Vic, Australia. [Villemagne, Victor L.; Rowe, Christopher C.] Univ Melbourne, Austin Hlth, Dept Med, Heidelberg, Vic, Australia. [Maruff, Paul] Cogstate Ltd, Melbourne, Vic, Australia. RP Pietrzak, RH (reprint author), US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, Clin Neurosci Div, VA Connecticut Healthcare Syst, 950 Campbell Ave 161E, West Haven, CT 06516 USA. EM robert.pietrzak@yale.edu RI Laws, Simon/C-2858-2014; OI Laws, Simon/0000-0002-4355-7082; Maruff, Paul/0000-0002-6947-9537 FU Commonwealth Scientific Industrial Research Organization (CSIRO); Edith Cowan University (ECU); Mental Health Research Institute (MHRI); National Ageing Research Institute (NARI); Austin Health; CogState Ltd.; National Health and Medical Research Council (NHMRC); Dementia Collaborative Research Centres program (DCRC2); Science and Industry Endowment Fund (SIEF); Cooperative Research Centre for Mental Health (CRCMH) FX Funding for the study was provided in part by the study partners [Commonwealth Scientific Industrial Research Organization (CSIRO), Edith Cowan University (ECU), Mental Health Research Institute (MHRI), National Ageing Research Institute (NARI), Austin Health, and CogState Ltd]. The study also received support from the National Health and Medical Research Council (NHMRC) and the Dementia Collaborative Research Centres program (DCRC2), as well as funding from the Science and Industry Endowment Fund (SIEF) and the Cooperative Research Centre for Mental Health (CRCMH). Robert H. Pietrzak, Yen Ying Lim, and Paul Maruff conceptualized the study design, reviewed the literature, and wrote the first draft of the article, and conducted data analyses; David Ames, Ralph N. Martins, Colin L. Masters, Paul Maruff, Victor L. Villemagne, Alan Rembach, Christopher C. Rowe are senior investigators of the AIBL study and responsible for the design of the AIBL study and selection of study endpoints. Victor L. Villemagne and Christopher C. Rowe conducted and oversaw neuroimaging for all participants. Yen Ying Lim and Karra Harrington conducted neuropsychological assessments. Simon M. Laws undertook genetic analyses for all participants. David Ames, Karra Harrington, Carolina Restrepo, Ralph N. Martins, Alan Rembach, Simon M. Laws, Colin L. Masters, Victor L. Villemagne, and Christopher C. Rowe provided critical revision of article drafts. NR 33 TC 16 Z9 16 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR PY 2015 VL 36 IS 3 BP 1231 EP 1238 DI 10.1016/j.neurobiolaging.2014.12.015 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA CI1XJ UT WOS:000354538100001 PM 25585532 ER PT J AU Quinzanos, I Luong, PT Bobba, S Richards, JS Majithia, V Davis, LA Caplan, L AF Quinzanos, I. Luong, P. T. Bobba, S. Richards, J. Steuart Majithia, V. Davis, L. A. Caplan, L. TI Validation of disease activity and functional status questionnaires in spondyloarthritis SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE ankylosing spondylitis; questionnaires; health impact assessment ID BATH ANKYLOSING-SPONDYLITIS; ACTIVITY INDEX; RELIABILITY; CRITERIA AB Objective Patients naive to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and to the Ankylosing Spondylitis Disease Activity Score (ASDAS) have voiced confusion in our clinics over the use of the term "AS" in these instruments. It is unknown whether these tools may be applied to other related forms of spondyloarthritis (SpA). The Bath Ankylosing Spondylitis Functional Index (BASFI) questionnaire also requires more definitive validation. We I) validated the BASFI against a standard definition of disability; and 2) validated slightly modified versions of the BASDAI and ASDAS questionnaires that replace references to "AS" with the term "inflammatory arthritis" for use in non-AS SpA. Methods Adult patients with SpA enrolled in the Veterans Affairs Program to Understand the Longterm outcomes in Spondylo-ARthritis (PULSAR) completed the BASFI, BASDAL ASDAS and altered versions of the BASDAI (PULSAR-modified Bath Disease Activity Index [PuBaDAI]) and ASDAS (PULSAR-modified Ankylosing Spondylitis Disease Activity Score [PuASDAS]). Spearman correlations and logistic regression were used to analyse the scores. Results The correlation between BASDAI and PuBaDAI and between ASDAS and PuASDAS scores was high (Spearman rho=0.92, p<0.001 and Spearman's rho=0.85, p<0.001, respectively). The test-retest correlation of BASFI was also high (Spearman's rho=0.92, p<0.001). The BASFI (OR 1.67, 95% C.I. 1.12-2.47), ASDAS (OR 1.34, 95% C.I. 1.02-1.76) and PuASDAS (OR 1.62, 95% C.I. 1.07-2.49) predicted federally-determined disability. Conclusion Preliminary data suggest that BASDAI and ASDAS scores correlate well with modified forms of these questionnaires and that the ASDAS, PuASDAS and BASFI are associated with disability. C1 [Quinzanos, I.; Luong, P. T.; Bobba, S.; Davis, L. A.; Caplan, L.] Dept Vet Affairs, Denver, CO USA. [Quinzanos, I.; Davis, L. A.; Caplan, L.] Univ Colorado, Sch Med, Aurora, CO USA. [Richards, J. Steuart] Dept Vet Affairs, Washington, DC USA. [Majithia, V.] Montgomery VAMC, Jackson, MS USA. [Davis, L. A.] Denver Hlth, Denver, CO USA. RP Caplan, L (reprint author), Univ Colorado, Sch Med, Denver Vet Affairs Med Ctr, 1775 Aurora Ct,POB 6511,B115, Denver, CO 80045 USA. EM liron.caplan@ucdenver.edu FU VA HSR&D Career Development Award [07-221]; NIH/NIAMS [T32 AR007534-24]; VA GME Enhancement Award FX L. Caplan is supported by VA HSR&D Career Development Award (07-221); L.A. Davis was supported by NIH/NIAMS T32 AR007534-24 and a VA GME Enhancement Award during the time this research was conducted. NR 18 TC 3 Z9 3 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD MAR-APR PY 2015 VL 33 IS 2 BP 146 EP 152 PG 7 WC Rheumatology SC Rheumatology GA CG6TX UT WOS:000353436400003 PM 25664820 ER PT J AU Riedl, MA Banerji, A Gower, R AF Riedl, Marc A. Banerji, Aleena Gower, Richard TI Current Medical Management of Hereditary Angioedema: Follow-up Survey of US Physicians SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Article DE Hereditary angioedema; C1-INH; ecallantide; Icatibant; Danazol; Antifibrinolytics; On-demand therapy; Long-term prophylaxis; Short-term prophylaxis; Self-administration; Home treatment ID QUALITY-OF-LIFE; C1 INHIBITOR DEFICIENCY; INTERNATIONAL CONSENSUS; C1-INHIBITOR DEFICIENCY; ACQUIRED ANGIOEDEMA; THERAPY; RECOMMENDATIONS; DEPRESSION; ATTACKS; PLASMA AB BACKGROUND: A physician survey conducted in the United States between October 2009 and February 2010 revealed wide variability in hereditary angioedema (HAE) management. OBJECTIVE: A follow-up survey was conducted to assess the impact of newly available treatment options and investigate changes in HAE care patterns. METHODS: Between March and June 2013, 6570 physicians were contacted, of whom, 245 HAE-treating physicians responded. Participants completed a 46-question online survey thatwas closely patterned after the initial survey. Although most data were analyzed descriptively, selected questions underwent statistical analysis to evaluate differences in treatment patterns between the 2 surveys. RESULTS: Compared with the prior survey, this follow-up survey found that the proportion of physicians who reported danazol as the preferred long-term prophylaxis agent declined from 56% to 23% (P < .00005); conversely, C1-esterase inhibitor increased in this category (20% to 57%; P < .00005). The percentage of attacks self-treated at home increased from 8% to 27% (P < .00005). Decreases were observed in emergency department visits (61% to 54%; P = not significant) and hospitalizations (13% to 3%; P = .0001) for HAE attacks. The percentage of patients perceived by physicians to be very satisfied with HAE treatment increased from 13% to 40% (P < .00005). In 2013, convenience was reported more frequently as an important patient factor that drove long-term prophylaxis choice (27% vs 10%; P < .00005), whereas adverse effects were cited less frequently (16% vs 42%; P < .00005); in both surveys, cost and/or insurance coverage was the greatest driver in this category (43% and 46%). CONCLUSION: Analysis of these findings suggests that the change in HAE treatment has increased self-treatment at home, decreased emergency department visits and/or hospitalizations, and provided greater patient satisfaction. (C) 2014 American Academy of Allergy, Asthma & Immunology C1 [Riedl, Marc A.] Univ Calif San Diego, Dept Med, Div Allergy Immunol & Rheumatol, La Jolla, CA 92039 USA. [Banerji, Aleena] Massachusetts Gen Hosp, Dept Med, Allergy & Immunol, Boston, MA 02114 USA. [Gower, Richard] Marycliff Allergy Specialists, Spokane, WA USA. RP Riedl, MA (reprint author), Univ Calif San Diego, Stein Clin Res Bldg,9500 Gilman Dr,Mail Code 0732, La Jolla, CA 92039 USA. EM mriedl@ucsd.edu FU CSL Behring FX Frank Rodino, MHS, PA, and Sandra Westra, PharmD, of Churchill Communications (Maplewood, NJ) assisted with the conduct of the survey and manuscript preparation, funded by CSL Behring. Statistical analysis was conducted by Thomas R. Sexton, PhD (Stony Brook University, Stony Brook, NY), also funded by CSL Behring. The authors retained full control over data interpretation and manuscript content. NR 35 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD MAR-APR PY 2015 VL 3 IS 2 BP 220 EP 227 DI 10.1016/j.jaip.2014.08.017 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA CH7JI UT WOS:000354211800010 PM 25609328 ER PT J AU Blumenthal, KG Wickner, PG Lau, JJ Zhou, L AF Blumenthal, Kimberly G. Wickner, Paige G. Lau, Jason J. Zhou, Li TI Stevens-Johnson syndrome and toxic epidermal necrolysis: A cross-sectional analysis of patients in an integrated allergy repository of a large health care system SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Letter ID DRUGS; MULTIFORME C1 [Blumenthal, Kimberly G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Rheumatol Allergy & Immunol, Boston, MA USA. [Wickner, Paige G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Lau, Jason J.; Zhou, Li] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gen Internal Med & Primary Care, Boston, MA 02115 USA. [Zhou, Li] Partners Healthcare Syst, Partners eCare, Clin Informat, Boston, MA USA. RP Blumenthal, KG (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Cox 201 Allergy Associates, Boston, MA 02114 USA. EM kblumenthal1@partners.org OI Blumenthal, Kimberly/0000-0003-4773-9817 FU AHRQ HHS [R01 HS022728, 1R01HS022728-01]; NHLBI NIH HHS [T32 HL116275] NR 12 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD MAR-APR PY 2015 VL 3 IS 2 BP 277 EP + DI 10.1016/j.jaip.2014.10.002 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA CH7JI UT WOS:000354211800020 PM 25609329 ER PT J AU Bortfeld, T Torresin, A Fiorino, C Andreo, P Gagliardi, G Jeraj, R Muren, LP Paiusco, M Thwaites, D Knoos, T AF Bortfeld, Thomas Torresin, Alberto Fiorino, Claudio Andreo, Pedro Gagliardi, Giovanna Jeraj, Robert Muren, Ludvig P. Paiusco, Marta Thwaites, David Knoos, Tommy TI The research versus clinical service role of medical physics SO RADIOTHERAPY AND ONCOLOGY LA English DT Editorial Material ID FUTURE C1 [Bortfeld, Thomas] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Bortfeld, Thomas] Harvard Univ, Sch Med, Boston, MA USA. [Torresin, Alberto] Osped Niguarda CaGranda Hosp, Dept Med Phys, Milan, Italy. [Fiorino, Claudio] Ist Sci San Raffaele, Dept Med Phys, I-20132 Milan, Italy. [Andreo, Pedro] Stockholm Univ, Karolinska Univ Hosp, Med Radiat Phys, Stockholm, Sweden. [Gagliardi, Giovanna] Karolinska Univ Hosp, Dept Med Phys, Sect Radiotherapy Phys & Engn, Karolinska, Sweden. [Jeraj, Robert] Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA. [Muren, Ludvig P.] Aarhus Univ, Aarhus Univ Hosp, Dept Med Phys, Aarhus, Denmark. [Paiusco, Marta] IOV, Dept Med Phys, Padua, Italy. [Thwaites, David] Univ Sydney, Inst Med Phys, Sydney, NSW 2006, Australia. [Knoos, Tommy] Skane Univ Hosp, Radiat Phys, Malmo, Sweden. [Knoos, Tommy] Lund Univ, Dept Med Radiat Phys, Clin Sci, S-22100 Lund, Sweden. RP Fiorino, C (reprint author), Ist Sci San Raffaele, Dept Med Phys, I-20132 Milan, Italy. NR 11 TC 3 Z9 3 U1 0 U2 12 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 MAR PY 2015 VL 114 IS 3 BP 285 EP 288 DI 10.1016/j.radonc.2015.02.003 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CH0UL UT WOS:000353737800001 PM 25727681 ER PT J AU Coroller, TP Grossmann, P Hou, Y Velazquez, ER Leijenaar, RTH Hermann, G Lambin, P Haibe-Kains, B Mak, RH Aerts, HJWL AF Coroller, Thibaud P. Grossmann, Patrick Hou, Ying Velazquez, Emmanuel Rios Leijenaar, Ralph T. H. Hermann, Gretchen Lambin, Philippe Haibe-Kains, Benjamin Mak, Raymond H. Aerts, Hugo J. W. L. TI CT-based radiomic signature predicts distant metastasis in lung adenocarcinoma SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Radiomics; Lung adenocarcinoma; NSCLC; Quantitative imaging; Biomarkers; Distant metastasis ID PHASE-III TRIAL; TEXTURE ANALYSIS; TUMOR VOLUME; FDG-PET; PROGNOSTIC-FACTOR; ONCOLOGY-GROUP; CANCER; RADIOTHERAPY; STAGE; SURVIVAL AB Background and purpose: Radiomics provides opportunities to quantify the tumor phenotype non-invasively by applying a large number of quantitative imaging features. This study evaluates computed-tomography (CT) radiomic features for their capability to predict distant metastasis (DM) for lung adenocarcinoma patients. Material and methods: We included two datasets: 98 patients for discovery and 84 for validation. The phenotype of the primary tumor was quantified on pre-treatment CT-scans using 635 radiomic features. Univariate and multivariate analysis was performed to evaluate radiomics performance using the concordance index (CI). Results: Thirty-five radiomic features were found to be prognostic (CI > 0.60, FDR < 5%) for DM and twelve for survival. It is noteworthy that tumor volume was only moderately prognostic for DM (CI = 0.55, p-value = 2.77 x 10(-5)) in the discovery cohort. A radiomic-signature had strong power for predicting DM in the independent validation dataset (CI = 0.61, p-value = 1.79 x 10(-17)). Adding this radiomic-signature to a clinical model resulted in a significant improvement of predicting DM in the validation dataset (p-value = 1.56 x 10(-11)). Conclusions: Although only basic metrics are routinely quantified, this study shows that radiomic features capturing detailed information of the tumor phenotype can be used as a prognostic biomarker for clinically-relevant factors such as DM. Moreover, the radiomic-signature provided additional information to clinical data. (c) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Coroller, Thibaud P.; Grossmann, Patrick; Hou, Ying; Velazquez, Emmanuel Rios; Hermann, Gretchen; Mak, Raymond H.; Aerts, Hugo J. W. L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Brigham & Womens Hosp, Boston, MA 02115 USA. [Aerts, Hugo J. W. L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol,Brigham & Womens Hosp, Boston, MA 02115 USA. [Coroller, Thibaud P.; Grossmann, Patrick; Leijenaar, Ralph T. H.; Lambin, Philippe; Aerts, Hugo J. W. L.] Maastricht Univ, Dept Radiat Oncol MAASTRO, GROW Res Inst, NL-6200 MD Maastricht, Netherlands. [Haibe-Kains, Benjamin] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. [Haibe-Kains, Benjamin] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. RP Coroller, TP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, 450 Brookline Ave,JF518, Boston, MA 02115 USA. EM tcoroller@lroc.harvard.edu; Hugo_Aerts@dfci.harvard.edu RI Haibe-Kains, Benjamin/D-3702-2011; Aerts, Hugo/P-6350-2015; OI Haibe-Kains, Benjamin/0000-0002-7684-0079; Aerts, Hugo/0000-0002-2122-2003; , Patrick/0000-0003-4918-6902; Coroller, Thibaud/0000-0001-7662-8724 FU National Institute of Health [NIH-USA U01CA190234]; QuIC-ConCePT project - EFPI A companies; Innovative Medicine Initiative Joint Undertaking (IMI JU) [115151]; Dutch technology Foundation STW [10696 DuCAT]; Technology Programme of the Ministry of Economic Affairs; EU 7th framework program (EURECA, ARTFORCE); NGI Pre-Seed Grant [93612005]; Kankeronderzoekfonds Limburg from the Health Foundation Limburg; Dutch Cancer Society [KWF UM 2011-5020, KWF UM 2009-4454, KWF MAC 2013-6089] FX Authors acknowledge financial support from the National Institute of Health (NIH-USA U01CA190234). Authors acknowledge financial support from the QuIC-ConCePT project, which is partly funded by EFPI A companies and the Innovative Medicine Initiative Joint Undertaking (IMI JU) under Grant Agreement No. 115151. This research is also supported by the Dutch technology Foundation STW (Grant No. 10696 DuCAT), which is the applied science division of NWO, and the Technology Programme of the Ministry of Economic Affairs. Authors also acknowledge financial support from EU 7th framework program (EURECA, ARTFORCE), NGI Pre-Seed Grant (No. 93612005), Kankeronderzoekfonds Limburg from the Health Foundation Limburg and the Dutch Cancer Society (KWF UM 2011-5020, KWF UM 2009-4454, KWF MAC 2013-6089). NR 39 TC 43 Z9 46 U1 9 U2 43 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 MAR PY 2015 VL 114 IS 3 BP 345 EP 350 DI 10.1016/j.radonc.2015.02.015 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CH0UL UT WOS:000353737800011 PM 25746350 ER PT J AU Bergen, SE Howrigan, D Sebat, J Neale, B Kendler, K AF Bergen, Sarah E. Howrigan, Daniel Sebat, Jonathan Neale, Benjamin Kendler, Kenneth TI CNVS AND POLYGENIC SCORES INTERACT TO CONTRIBUTE TO SCHIZOPHRENIA RISK SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Bergen, Sarah E.] Karolinska Inst, Med Epidemiol & Biostat, Stockholm, Sweden. [Kendler, Kenneth] Virginia Commonwealth Univ, Virginia Inst Psychiat Genet, Richmond, VA USA. [Sebat, Jonathan] Univ Calif San Diego, Psychiat & Cellular & Mol Med, San Diego, CA 92103 USA. [Howrigan, Daniel; Neale, Benjamin] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Bergen, Sarah E.; Neale, Benjamin] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2118820 BP S198 EP S198 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200523 ER PT J AU Blokland, GAM Petryshen, TL AF Blokland, Gabriella Antonina Maria Petryshen, Tracey Lynn TI BIG SCIENCE: HARMONIZING NEUROPSYCHOLOGICAL MEASURES FROM MULTIPLE SAMPLES FOR GENETIC ASSOCIATION ANALYSIS IN THE GENUS CONSORTIUM SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Blokland, Gabriella Antonina Maria; Petryshen, Tracey Lynn] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Human Genet Res, Psychiat & Neurodev Genet Unit,Dept Psychiat, Boston, MA USA. [Blokland, Gabriella Antonina Maria; Petryshen, Tracey Lynn] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02139 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 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2118755 BP S69 EP S69 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200185 ER PT J AU Cai, HL Li, HD Yao, JK AF Cai, HuaLin Li, HuanDe Yao, Jeffrey K. TI A POTENTIAL MECHANISM UNDERLYING ATYPICAL ANTIPSYCHOTIC INDUCED LIPID DISTURBANCES SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Cai, HuaLin; Li, HuanDe] Cent S Univ, Xiangya Hosp 2, Changsha, Hunan, Peoples R China. [Cai, HuaLin; Yao, Jeffrey K.] Cent S Univ, Inst Clin Pharm, Changsha, Hunan, Peoples R China. [Cai, HuaLin; Yao, Jeffrey K.] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA USA. [Cai, HuaLin; Yao, Jeffrey K.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Yao, Jeffrey K.] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA 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 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2095377 BP S124 EP S125 PG 2 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200330 ER PT J AU Carrion, RE John, M Addington, J Bearden, CE Cadenhead, K Mathalon, D McGlashan, T Perkins, D Seidman, LJ Tsuang, M Walker, E Woods, S Cannon, T Cornblatt, B AF Carrion, Ricardo E. John, Majnu Addington, Jean Bearden, Carrie E. Cadenhead, Kristin Mathalon, Daniel McGlashan, Thomas Perkins, Diana Seidman, Larry J. Tsuang, Ming Walker, Elaine Woods, Scott Cannon, Tyrone Cornblatt, Barbara TI THE DEVELOPMENTAL COURSE OF SOCIAL AND ROLE FUNCTIONING IN THE PRODROMAL STAGES OF PSYCHOSIS SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Carrion, Ricardo E.; John, Majnu; Cornblatt, Barbara] Zucker Hillside Hosp, Psychiat Res, Glen Oaks, NE USA. [Carrion, Ricardo E.; Cornblatt, Barbara] Hofstra North Shore LIJ Sch Med, Psychiat, Hempstead, NY USA. [John, Majnu] Feinstein Inst Med Res, Ctr Psychiat Neurosci, Manhasset, NY USA. [Addington, Jean] Univ Calgary, Psychiat, Calgary, AB T2N 1N4, Canada. [Bearden, Carrie E.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Cadenhead, Kristin] Univ Calif San Diego, Psychiat, San Diego, CA 92103 USA. [McGlashan, Thomas; Woods, Scott; Cannon, Tyrone] Yale Univ, Psychol, New Haven, CT USA. [McGlashan, Thomas; Woods, Scott; Cannon, Tyrone] Yale Univ, Psychiat, New Haven, CT USA. [Mathalon, Daniel] Univ Calif San Francisco, Psychiat, San Francisco, CA 94143 USA. [Perkins, Diana] Univ N Carolina, Psychiat, Chapel Hill, NC USA. [Seidman, Larry J.; Tsuang, Ming] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Psychiat, Boston, MA 02215 USA. [Seidman, Larry J.; Tsuang, Ming] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Walker, Elaine] Emory Univ, Psychol, Atlanta, GA 30322 USA. 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 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2118187 BP S164 EP S164 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200431 ER PT J AU Chen, Y Maher, S Ekstrom, T Holt, D Ongur, D AF Chen, Yue Maher, Stephen Ekstrom, Tor Holt, Daphne Ongur, Dost TI THE FACE PROCESSING SYSTEM IN SCHIZOPHRENIA DOES NOT POSSESS A CORE FUNCTIONAL PROPERTY: FACE-SELECTIVITY SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Chen, Yue; Maher, Stephen; Ekstrom, Tor; Ongur, Dost] Harvard Univ, McLean Hosp, Sch Med, Belmont, MA USA. [Holt, Daphne] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, 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 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2083578 BP S71 EP S71 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200189 ER PT J AU Chung, Y Jacobson, A He, G van Erp, T McEwen, S Addington, J Bearden, C Cadenhead, K Cornblatt, B Mathalon, D McGlashan, T Perkins, D Seidman, LJ Tsuang, M Walker, E Woods, S Heinssen, R Cannon, T AF Chung, Yoonho Jacobson, Aims He, George van Erp, T. McEwen, Sarah Addington, Jean Bearden, Carrie Cadenhead, Kristin Cornblatt, Barbara Mathalon, Daniel McGlashan, Thomas Perkins, Diana Seidman, Larry J. Tsuang, Ming Walker, Elaine Woods, Scott Heinssen, Robert Cannon, Tyrone TI PRODROMAL SYMPTOM SEVERITY PREDICTS ACCELERATED GRAY MATTER REDUCTION AND THIRD VENTRICLE EXPANSION AMONG CLINICALLY HIGH RISK YOUTH DEVELOPING PSYCHOTIC DISORDERS SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Chung, Yoonho; Jacobson, Aims; He, George; Cannon, Tyrone] Yale Univ, Psychol, New Haven, CT USA. [van Erp, T.] UC Irvine, Psychiat & Human Behav, Irvine, CA USA. [McEwen, Sarah; Bearden, Carrie] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [McEwen, Sarah; Bearden, Carrie] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Addington, Jean] Univ Calgary, Psychiat, Calgary, AB, Canada. [Cadenhead, Kristin; Tsuang, Ming] UCSD San Diego, Psychiat, La Jolla, CA USA. [Cornblatt, Barbara] Zucker Hillside, Psychiat, Glen Oaks, NY USA. [Mathalon, Daniel] UCSF, Psychiany, San Francisco, CA USA. [McGlashan, Thomas; Woods, Scott] Yale Univ, Psychiat, New Haven, CT USA. [Perkins, Diana] Univ N Carolina, Psychiat, Chapel Hill, NC USA. [Perkins, Diana] Univ N Carolina, Renaissance Comp Inst, Chapel Hill, NC USA. [Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Psychiat, Cambridge, MA USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Psychiat, Cambridge, MA USA. [Walker, Elaine] Emory Univ, Psychol, Atlanta, GA 30322 USA. [Heinssen, Robert] NIMH, Div Treatment & Prevent Res, Bethesda, MD 20892 USA. 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 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 BP S249 EP S249 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200658 ER PT J AU Cortes-Briones, JA Cahill, JD Skosnik, PD Mathalon, DH Williams, A Sewell, RA Roach, BJ Ford, JM Ranganathan, M D'Souza, DC AF Cortes-Briones, Jose A. Cahill, John Daniel Skosnik, Patrick David Mathalon, Daniel H. Williams, Ashley Sewell, Richard Andrew Roach, Brian J. Ford, Judith M. Ranganathan, Mohini D'Souza, Deepak Cyril TI INCREASED NEURAL NOISE IS RELATED TO THE PSYCHOSIS-LIKE EFFECTS OF THC SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Cortes-Briones, Jose A.; Cahill, John Daniel; Skosnik, Patrick David; Williams, Ashley; Sewell, Richard Andrew; Ranganathan, Mohini; D'Souza, Deepak Cyril] VA Connecticut Healthcare Syst, Psychiat Serv, West Haven, CT USA. [Cortes-Briones, Jose A.; Cahill, John Daniel; Skosnik, Patrick David; Williams, Ashley; Sewell, Richard Andrew; Ranganathan, Mohini; D'Souza, Deepak Cyril] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Mathalon, Daniel H.; Ford, Judith M.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Mathalon, Daniel H.; Roach, Brian J.; Ford, Judith M.] San Francisco VA Med Ctr, Mental Hlth Serv Line, San Francisco, CA USA. RI Skosnik, Patrick/D-6466-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2119314 BP S16 EP S16 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200041 ER PT J AU Curcio, N Mervis, JE Bisoglio, J Fiszdon, JM Reddy, F Choi, J AF Curcio, Nicholas Mervis, Joshua E. Bisoglio, Joseph Fiszdon, Joanna M. Reddy, Felice Choi, Jimmy TI ANTICIPATORY PLEASURE AND ITS IMPLICATIONS ON LEARNING IN SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Curcio, Nicholas; Mervis, Joshua E.; Bisoglio, Joseph; Choi, Jimmy] Columbia Univ, Neurocognit Rehabil Res Lab, Med Ctr, New York, NY USA. [Fiszdon, Joanna M.] Yale Univ, Sch Med, VA Connecticut Healthcare Syst, New Haven, CT USA. [Reddy, Felice] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Reddy, Felice] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2118001 BP S166 EP S167 PG 2 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200438 ER PT J AU Davis, MC Wynn, JK Weiner, K Hellemann, GS Green, MF Marder, SR AF Davis, Michael C. Wynn, J. K. Weiner, Katherine Hellemann, Gerhard S. Green, Michael F. Marder, Stephen R. TI RANDOMIZED CONTROLLED TRIAL OF N-ACETYLCYSTEINE FOR COGNITION AND EEG CORRELATES IN SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Davis, Michael C.] Baylor Coll Med, Psychiat & Behav Sci, Houston, TX 77030 USA. [Wynn, J. K.; Weiner, Katherine; Hellemann, Gerhard S.; Green, Michael F.; Marder, Stephen R.] UCLA Semel Inst, Psychiat & Biobehav Sci, Los Angeles, CA USA. [Wynn, J. K.; Weiner, Katherine; Green, Michael F.; Marder, Stephen R.] VA Greater Los Angeles, Mental Illness Res Educ & Clin Ctr, Los Angeles, CA USA. [Davis, Michael C.] Michael E DeBakey VA Med Ctr, Mental Hlth Care Line, Houston, TX USA. 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 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2086799 BP S308 EP S309 PG 2 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200812 ER PT J AU del Re, EC Gao, Y Eckbo, R Petryshen, TL Blokland, GAM Seidman, LJ Mesholam-Gately, RI Goldstein, J Kubicki, M McCarley, RW Shenton, ME Bouix, S AF del Re, Elisabetta C. Gao, Yi Eckbo, Ryan Petryshen, Tracey L. Blokland, Gabriella A. M. Seidman, Larry J. Mesholam-Gately, Raquelle I. Goldstein, Jill Kubicki, Marek McCarley, Robert W. Shenton, Martha E. Bouix, Sylvain TI MULTI-ATLAS BRAIN MASKING FOR MRI ANALYSIS IN CONTROLS AND SCHIZOPHRENIA: COMPARISON WITH OTHER MASKING TECHNIQUES AND MANUAL MASKING SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [del Re, Elisabetta C.; McCarley, Robert W.; Shenton, Martha E.; Bouix, Sylvain] VA Boston Healthcare Syst, Psychiat, Brockton, MA USA. [del Re, Elisabetta C.; McCarley, Robert W.; Shenton, Martha E.; Bouix, Sylvain] Harvard Univ, Sch Med, Brockton, MA 02401 USA. [del Re, Elisabetta C.; Gao, Yi; Eckbo, Ryan; Kubicki, Marek; Shenton, Martha E.; Bouix, Sylvain] Harvard Univ, Brigham & Womens Hosp, Sch Med, Psychiat, Boston, MA 02115 USA. [Gao, Yi; Seidman, Larry J.; Mesholam-Gately, Raquelle I.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Massachusetts Mental Hlth Ctr,Publ Psychiat Div, Boston, MA 02215 USA. [Petryshen, Tracey L.; Blokland, Gabriella A. M.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Petryshen, Tracey L.; Blokland, Gabriella A. M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Goldstein, Jill] Harvard Univ, Brigham & Womens Hosp, Sch Med, Psychiat & Med, Boston, MA 02115 USA. [Petryshen, Tracey L.; Blokland, Gabriella A. M.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Seidman, Larry J.; Goldstein, Jill] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat, Boston, MA USA. 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 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2117752 BP S252 EP S253 PG 2 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200668 ER PT J AU DeLisi, LE AF DeLisi, Lynn Eleanor TI LANGUAGE PATHWAYS IN THE BRAIN AND THEIR BASIS FOR THE SYMPTOMS OF SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [DeLisi, Lynn Eleanor] Va Boston Healthcare, Psychiat, Boston, MA USA. [DeLisi, Lynn Eleanor] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2147964 BP S222 EP S222 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200587 ER PT J AU Demyanovich, H Feldman, S Jackson, J Eaton, W Cascella, NG Fasano, A Santora, D Sullivan, KM Raley, H McMahon, R Carpenter, WT Kelly, D AF Demyanovich, Haley Feldman, Stephanie Jackson, Jessica Eaton, William Cascella, Nicola G. Fasano, Alessio Santora, Debby Sullivan, Kelli Marie Raley, Heather McMahon, Robert Carpenter, William T. Kelly, Deanna TI THE RELATIONSHIP BETWEEN GLUTEN SENSITIVITY AND PSYCHIATRIC SYMPTOMS IN PEOPLE WITH SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Demyanovich, Haley; Feldman, Stephanie; Sullivan, Kelli Marie; McMahon, Robert; Carpenter, William T.; Kelly, Deanna] Univ Maryland, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Jackson, Jessica] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [Eaton, William] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Cascella, Nicola G.] Sheppard Pratt Hosp, Neuropsychiat, Baltimore, MD USA. [Fasano, Alessio] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Santora, Debby] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Raley, Heather] NIDA, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2092944 BP S17 EP S17 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200043 ER PT J AU Glynn, SM Gingerich, S Mueser, KT Cather, C Penn, D AF Glynn, Shirley M. Gingerich, Susan Mueser, Kim T. Cather, Cori Penn, David TI THE ROLE OF FAMILY INTERVENTION IN COORDINATED SPECIALTY CARE FOR FIRST EPISODE PSYCHOSIS SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Glynn, Shirley M.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Penn, David] UNC, Psychol, Chapel Hill, NC USA. [Cather, Cori] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Cather, Cori] Harvard Univ, Med Schoo, Boston, MA 02115 USA. [Mueser, Kim T.] Boston Univ, Ctr Psychiat Rehabil, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2141449 BP S173 EP S173 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200455 ER PT J AU Greenwood, TA Lazzeroni, LC Calkins, ME Freedman, R Green, MF Gur, RE Gur, RC Light, GA Nuechterlein, KH Olincy, A Radant, AD Seidman, LJ Siever, LJ Silverman, JM Stone, WS Sugar, CA Swerdlow, NR Tsuang, DW Tsuang, MT Turetsky, BI Braff, DL AF Greenwood, Tiffany A. Lazzeroni, Laura C. Calkins, Monica E. Freedman, Robert Green, Michael F. Gur, Raquel E. Gur, Ruben C. Light, Gregory A. Nuechterlein, Keith H. Olincy, Ann Radant, Allen D. Seidman, Larry J. Siever, Larry J. Silverman, Jeremy M. Stone, William S. Sugar, Catherine A. Swerdlow, Neal R. Tsuang, Debby W. Tsuang, Ming T. Turetsky, Bruce I. Braff, David L. TI GENETIC ASSESSMENT OF CANDIDATE ENDOPHENOTYPES FROM THE CONSORTIUM ON THE GENETICS OF SCHIZOPHRENIA FAMILY STUDY SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Greenwood, Tiffany A.; Light, Gregory A.; Swerdlow, Neal R.; Tsuang, Ming T.; Braff, David L.] Univ Calif San Diego, Psychiat, La Jolla, CA 92093 USA. [Lazzeroni, Laura C.] Stanford Univ, Psychiat & Behav Sci, Stanford, CA 94305 USA. [Calkins, Monica E.; Gur, Raquel E.; Gur, Ruben C.; Turetsky, Bruce I.] Univ Penn, Psychiat, Philadelphia, PA 19104 USA. [Freedman, Robert; Olincy, Ann] Univ Colorado, Hlth Sci Ctr, Psychiat, Denver, CO USA. [Green, Michael F.; Nuechterlein, Keith H.] Univ Calif Los Angeles, Psychiat & Biobehav Sci, Los Angeles, CA USA. [Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Light, Gregory A.] VA San Diego Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 22, San Diego, CA USA. [Radant, Allen D.; Tsuang, Debby W.] Univ Washington, Psychiat & Behav Sci, Seattle, WA 98195 USA. [Radant, Allen D.; Tsuang, Debby W.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Seidman, Larry J.; Stone, William S.] Harvard Univ, Sch Med, Psychiat, Boston, MA USA. [Seidman, Larry J.; Stone, William S.] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02215 USA. [Siever, Larry J.; Silverman, Jeremy M.] Mt Sinai Sch Med, Psychiat, New York, NY USA. [Siever, Larry J.; Silverman, Jeremy M.] James J Peters VA Med Ctr, New York, NY USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Sch Publ Hlth, Biostat, Los Angeles, CA 90024 USA. [Tsuang, Ming T.] Harvard Inst Psychiat Epidemiol & Genet, 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 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2117107 BP S203 EP S203 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200538 ER PT J AU Haas, GL Honsaker, SM Horton, LE Luther, JF Flounders, MW AF Haas, Gretchen L. Honsaker, Sarah M. Horton, Leslie E. Luther, James F. Flounders, Matthew W. TI DOES GENDER EXERT A MODERATING INFLUENCE ON SOCIAL PERSPECTIVE-TAKING IN SCHIZOPHRENIA? SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Haas, Gretchen L.] Univ Pittsburgh, Psychiat & Psychol, Pittsburgh, PA USA. [Horton, Leslie E.; Flounders, Matthew W.] Univ Pittsburgh, Psychiat, Pittsburgh, PA USA. [Haas, Gretchen L.; Honsaker, Sarah M.; Horton, Leslie E.; Luther, James F.; Flounders, Matthew W.] VA Pittsburgh Healthcare Syst, MIRECC, Pittsburgh, PA USA. [Luther, James F.] Univ Pittsburgh, Epidemiol, Pittsburgh, PA USA. [Honsaker, Sarah M.] Univ Pittsburgh, Psychol, Pittsburgh, PA 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 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2117931 BP S77 EP S77 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200206 ER PT J AU Haut, KM Addington, J Bearden, CE Cadenhead, K Cornblatt, B Mathalon, D McGlashan, TH Perkins, DO Seidman, LJ Tsuang, M Walker, E Woods, S Heinssen, R Cannon, T AF Haut, Kristen M. Addington, Jean Bearden, Carrie E. Cadenhead, Kristin Cornblatt, Barbara Mathalon, Daniel McGlashan, Thomas H. Perkins, Diana O. Seidman, Larry J. Tsuang, Ming Walker, Elaine Woods, Scott Heinssen, Robert Cannon, Tyrone TI REDUCED WHITE MATTER INTEGRITY IN A MULTISITE LONGITUDINAL STUDY OF YOUTH AT RISK FOR PSYCHOSIS SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Haut, Kristen M.; Cannon, Tyrone] Yale Univ, Psychol, New Haven, CT USA. [Addington, Jean] Univ Calgary, Hotchkiss Brain Inst, Psychiat, Calgary, AB T2N 1N4, Canada. [Bearden, Carrie E.] Univ Calif Los Angeles, Psychiat & Biobehav Sci & Psychol, Los Angeles, CA USA. [Cadenhead, Kristin] Univ Calif San Diego, Psychiat, San Diego, CA 92103 USA. [McGlashan, Thomas H.; Woods, Scott; Cannon, Tyrone] Yale Univ, Psychiat, New Haven, CT USA. [Cornblatt, Barbara] Zucker Hillside Hosp, Psychiat, Long Isl City, NY USA. [Mathalon, Daniel] Univ Calif San Francisco, Psychiat, San Francisco, CA 94143 USA. [Perkins, Diana O.] Univ N Carolina, Psychiat, Chapel Hill, NC USA. [Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Harvard Med Sch, Psychiat, Boston, MA 02215 USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tsuang, Ming] Univ Calif San Diego, Ctr Behav Genom, Inst Genom Med, Psychiat, La Jolla, CA 92093 USA. [Walker, Elaine] Emory Univ, Psychol & Psychiat, Atlanta, GA 30322 USA. [Heinssen, Robert] NIMH, Div Adulta Translat Res & Treatment Dev, Bethesda, MD 20892 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 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2083088 BP S257 EP S257 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200679 ER PT J AU Hirano, Y Oribe, N Onitsuka, T Kanba, S Mesholam-Gately, R Seidman, LJ Niznikiewicz, MA McCarley, RW Spencer, KM AF Hirano, Yoji Oribe, Naoya Onitsuka, Toshiaki Kanba, Shigenobu Mesholam-Gately, Raquelle Seidman, Larry J. Niznikiewicz, Margaret A. McCarley, Robert W. Spencer, Kevin M. TI PROGRESSIVE AUDITORY GAMMA OSCILLATION DEFICIT IN CLINICAL HIGH-RISK SUBJECTS AND FIRST-EPISODE SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Hirano, Yoji; Oribe, Naoya; Spencer, Kevin M.] VA Boston Healthcare Syst, Neural Dynam Lab, Psychiat, Boston, MA USA. [Hirano, Yoji; Oribe, Naoya; Mesholam-Gately, Raquelle; Seidman, Larry J.; Spencer, Kevin M.] Harvard Univ, Sch Med, Boston, MA USA. [Hirano, Yoji; Oribe, Naoya; Onitsuka, Toshiaki; Kanba, Shigenobu] Kyushu Univ, Grad Sch Med Sci, Neuropsychiat, Fukuoka 812, Japan. [Mesholam-Gately, Raquelle; Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Psychiat, Boston, MA 02215 USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Niznikiewicz, Margaret A.; McCarley, Robert W.] VA Boston Healthcare Syst, Lab Neurosci, Psychiat, Brockton, MA USA. [Niznikiewicz, Margaret A.; McCarley, Robert W.] Harvard Univ, Sch Med, Brockton, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2087079 BP S19 EP S20 PG 2 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200051 ER PT J AU Holt, D Boeke, E Coombs, G DeCross, S Rauch, S Tootell, R AF Holt, Daphne Boeke, Emily Coombs, Garth DeCross, Stephanie Rauch, Scott Tootell, Roger TI A SENSORY-MOTOR SYSTEM MEDIATING LOWER AND HIGHER-LEVEL SOCIAL DISTANCE SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Holt, Daphne; DeCross, Stephanie] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Holt, Daphne; Rauch, Scott; Tootell, Roger] Harvard Univ, Sch Med, Boston, MA USA. [Boeke, Emily] NYU, Psychol, New York, NY USA. [Coombs, Garth] Harvard Univ, Psychol, Cambridge, MA 02138 USA. [Rauch, Scott] McLean Hosp, Belmont, MA 02178 USA. [Tootell, Roger] Massachusetts Gen Hosp, Radiol, Boston, MA 02114 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 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2117720 BP S78 EP S78 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200209 ER PT J AU Horan, WP Marder, SR Green, M AF Horan, William Powers Marder, Stephen R. Green, Michael TI FURTHER VALIDATION OF A "SECOND GENERATION" CLINICAL ASSESSMENT MEASURE OF NEGATIVE SYMPTOMS SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Horan, William Powers; Marder, Stephen R.; Green, Michael] VA Greater Los Angeles Healthcare Syst, Psychiat, Los Angeles, CA USA. [Horan, William Powers; Marder, Stephen R.; Green, Michael] Univ Calif Los Angeles, Psychiat & Biobehav Sci, Los Angeles, CA 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 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2096158 BP S108 EP S109 PG 2 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200291 ER PT J AU Horton, LE Michael, VC Haas, GL AF Horton, Leslie E. Michael, V. C. Haas, Gretchen L. TI EMOTION-BASED DECISION-MAKING IN THOSE AT HIGH RISK FOR SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Horton, Leslie E.; Michael, V. C.; Haas, Gretchen L.] Univ Pittsburgh, Sch Med, Psychiat, Pittsburgh, PA USA. [Haas, Gretchen L.] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA 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 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2081626 BP S49 EP S49 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200132 ER PT J AU Jimenez, AM Lee, J Wynn, JK Horan, WP Green, MF AF Jimenez, Amy M. Lee, Junghee Wynn, J. K. Horan, William Powers Green, Michael F. TI SELF-REFERENTIAL MEMORY IN SCHIZOPHRENIA: AN FMRI STUDY SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Jimenez, Amy M.; Lee, Junghee; Wynn, J. K.; Horan, William Powers; Green, Michael F.] Vet Affairs Greater Los Angeles Healthcare Syst, Desert Pacific MIRECC, Los Angeles, CA USA. [Jimenez, Amy M.; Lee, Junghee; Wynn, J. K.; Horan, William Powers; Green, Michael F.] Univ Calif Los Angeles, Psychiat & Biobehav Sci, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2115433 BP S81 EP S81 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200216 ER PT J AU Kern, RS Zarate, R Glynn, SM Smith, KM Reddy, F Mitchell, SS Turner, LR Iglesias, J Maes, L McNair, A Liberman, RP Kopelowicz, A Green, MF AF Kern, Robert S. Zarate, R. Glynn, Shirley M. Smith, K. M. Reddy, Felice Mitchell, S. S. Turner, Luana R. Iglesias, J. Maes, L. McNair, A. Liberman, R. P. Kopelowicz, A. Green, Michael F. TI THE EFFECTS OF ERRORLESS LEARNING ON WORK OUTCOME IN SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Kern, Robert S.; Zarate, R.; Glynn, Shirley M.; Smith, K. M.; Mitchell, S. S.; Turner, Luana R.; Iglesias, J.; Maes, L.; McNair, A.; Liberman, R. P.; Kopelowicz, A.; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Kern, Robert S.; Glynn, Shirley M.; Reddy, Felice; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Dept Vet Affairs VISN MIRECC 22, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2083573 BP S178 EP S178 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200469 ER PT J AU Kikinis, Z Fitzsimmons, J Dunn, C Vu, MA Makris, N Bouix, S Goldstein, J Mesholam-Gately, RI Petryshen, T del Re, EC Wojcik, J Seidman, LJ McCarley, RW Shenton, ME Kubicki, M AF Kikinis, Zora Fitzsimmons, Jennifer Dunn, Chandler Mai-Anh Vu Makris, Nikos Bouix, Sylvain Goldstein, Jill Mesholam-Gately, Raquelle I. Petryshen, Tracey del Re, Elisabetta C. Wojcik, Joanne Seidman, Larry J. McCarley, Robert W. Shenton, Martha E. Kubicki, Marek TI ANTERIOR COMMISSURAL WHITE MATTER FIBER ABNORMALITIES IN FIRST-EPISODE PSYCHOSIS: A TRACTOGRAPHY STUDY SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Kikinis, Zora; Fitzsimmons, Jennifer; Dunn, Chandler; Mai-Anh Vu; Makris, Nikos; Bouix, Sylvain; Goldstein, Jill; Shenton, Martha E.; Kubicki, Marek] Brigham & Womens Hosp, Psychiat, Boston, MA 02115 USA. [Makris, Nikos; Petryshen, Tracey; Seidman, Larry J.] Massachusetts Gen Hosp, Psychiat, Charlestown, MA USA. [Goldstein, Jill] Brigham & Womens Hosp, Med, Boston, MA 02115 USA. [Mesholam-Gately, Raquelle I.; Wojcik, Joanne; Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Publ Psychiat Div, Boston, MA 02215 USA. [Petryshen, Tracey] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [del Re, Elisabetta C.; McCarley, Robert W.; Shenton, Martha E.] VA Boston Healthcare Syst, Psychiat, Brockton, MA USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2118903 BP S260 EP S261 PG 2 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200687 ER PT J AU Levitt, JJ Rathi, Y Raviv, TR Nestor, PG Levin, L McCarley, RW Shenton, ME AF Levitt, James J. Rathi, Yogesh Raviv, Tammy R. Nestor, Paul G. Levin, Laura McCarley, Robert W. Shenton, Martha E. TI FRONTOSTRIATAL DYSCONNECTIVITY IN SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Levitt, James J.; Nestor, Paul G.; McCarley, Robert W.; Shenton, Martha E.] Harvard Univ, VA Boston Healthcare Syst, Psychiat, Sch Med, Brockton, MA 02401 USA. [Levitt, James J.; Rathi, Yogesh; Raviv, Tammy R.; Levin, Laura; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Psychiat Neuroimaging Lab, Psychiat,Med Sch, Boston, MA 02115 USA. RI Riklin Raviv, Tammy/A-3462-2013 NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2086698 BP S263 EP S263 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200694 ER PT J AU Lyall, AE Savadjiev, P del Re, E O'Donnell, L Seidman, LJ Goldstein, J Mesholam-Gately, R Petryshen, T Wojcik, J McCarley, RW Shenton, ME Kubicki, M AF Lyall, Amanda E. Savadjiev, Peter del Re, Elisabetta O'Donnell, Lauren Seidman, Larry J. Goldstein, Jill Mesholam-Gately, Raquelle Petryshen, Tracey Wojcik, Joanne McCarley, Robert W. Shenton, Martha E. Kubicki, Marek TI EXPLORING THE RELATIONSHIP OF GRAY AND WHITE MATTER STRUCTURAL PATHOLOGY IN FIRST-EPISODE SCHIZOPHRENIA THROUGH MUTUAL INFORMATION SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO ID BRAIN-DEVELOPMENT C1 [Lyall, Amanda E.; Savadjiev, Peter; del Re, Elisabetta; Shenton, Martha E.; Kubicki, Marek] Harvard Univ, Brigham & Womens Hosp, Psychiat Neuroimaging Lab, Sch Med, Boston, MA 02115 USA. [Lyall, Amanda E.] Harvard Univ, Sch Med, Judge Bakers Children Ctr, Boston, MA USA. [Savadjiev, Peter; O'Donnell, Lauren] Harvard Univ, Sch Med, Lab Math Imaging, Boston, MA USA. [Seidman, Larry J.; Goldstein, Jill; Mesholam-Gately, Raquelle; Wojcik, Joanne] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Boston, MA USA. [Seidman, Larry J.; Petryshen, Tracey] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [del Re, Elisabetta; Goldstein, Jill] Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Petryshen, Tracey] VA Boston Healthcare Syst, Res & Dev, Boston, MA USA. [McCarley, Robert W.; Shenton, Martha E.] VA Boston Healthcare Syst, Brockton, MA USA. NR 5 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2116580 BP S264 EP S264 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200696 ER PT J AU McCleery, A Lee, J Wynn, JK Subotnik, KL Ventura, J Ghermezi, L Hayata, JN Pascual, GN Green, MF Nuechterlein, KH AF McCleery, Amanda Lee, Junghee Wynn, Jonathan K. Subotnik, Kenneth L. Ventura, Joseph Ghermezi, Livon Hayata, Jacqueline N. Pascual, Gabrielle N. Green, Michael F. Nuechterlein, Keith H. TI SOCIAL COGNITION ACROSS PHASE OF ILLNESS IN SCHIZOPHRENIA: AN EXAMINATION OF LOW-LEVEL AND HIGH-LEVEL PROCESSES SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [McCleery, Amanda; Lee, Junghee; Wynn, Jonathan K.; Subotnik, Kenneth L.; Ventura, Joseph; Ghermezi, Livon; Hayata, Jacqueline N.; Pascual, Gabrielle N.; Green, Michael F.; Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Wynn, Jonathan K.; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, MIRECC, Los Angeles, CA USA. [Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. 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 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 BP S55 EP S56 PG 2 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200149 ER PT J AU Michaels, TM Horan, WP Ginger, EJ Martinovich, Z Pinkham, A Smith, MJ AF Michaels, Tania Marie Horan, William Powers Ginger, E. J. Martinovich, Z. Pinkham, Amy Smith, Matthew James TI COGNITIVE EMPATHY CONTRIBUTES TO POOR SOCIAL FUNCTIONING IN SCHIZOPHRENIA: EVIDENCE FROM A NEW SELF-REPORT MEASURE OF COGNITIVE AND AFFECTIVE EMPATHY SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Michaels, Tania Marie; Ginger, E. J.; Martinovich, Z.; Smith, Matthew James] Northwestern Univ, Dept Psychiat & Behav Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [Horan, William Powers] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Horan, William Powers] VA Greater Los Angeles Healthcare Syst, MIRECC VISN22, Los Angeles, CA USA. [Pinkham, Amy] Univ Texas Dallas, Sch Behav & Brain Sci, Richardson, TX 75083 USA. [Smith, Matthew James] Northwestern Univ, Warren Wright Adolescent Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. 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 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 BP S56 EP S56 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200150 ER PT J AU Pasternak, O Durgun, I Zuo, J Mesholam-Gately, RI Goldstein, JM Seidman, LJ McCarley, RW Kubicki, M Shenton, ME AF Pasternak, Ofer Durgun, Irem Zuo, Jessica Mesholam-Gately, Raquelle I. Goldstein, Jill M. Seidman, Larry J. McCarley, Robert W. Kubicki, Marek Shenton, Martha E. TI POSITIVE SYMPTOMS IN FIRST EPISODE SCHIZOPHRENIA PATIENTS CORRELATE WITH EXCESSIVE EXTRACELLULAR SPACE SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Pasternak, Ofer; Kubicki, Marek; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Psychiat & Radiol, Sch Med, Boston, MA 02115 USA. [Durgun, Irem; Zuo, Jessica] Harvard Univ, Brigham & Womens Hosp, Psychiat, Sch Med, Boston, MA 02115 USA. [Mesholam-Gately, Raquelle I.; Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02215 USA. [Mesholam-Gately, Raquelle I.; Seidman, Larry J.; McCarley, Robert W.] Harvard Univ, Sch Med, Psychiat, Boston, MA USA. [Goldstein, Jill M.] Harvard Univ, Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Med Sch, Boston, MA 02115 USA. [Goldstein, Jill M.] Harvard Univ, Sch Med, Psychiat & Med, Boston, MA USA. [McCarley, Robert W.; Shenton, Martha E.] VA Boston Healthcare Syst, Brockton, MA USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2085277 BP S269 EP S269 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200709 ER PT J AU Reddy, F Kern, RS Smith, KM Mitchell, S Glynn, SM Turner, LR Zarate, R Kopelowicz, A Green, MF AF Reddy, Felice Kern, Robert S. Smith, K. M. Mitchell, Sharon Glynn, Shirley M. Turner, Luana R. Zarate, Roberto Kopelowicz, Alex Green, Michael F. TI PREDICTORS OF EMPLOYMENT IN ADULTS WITH SCHIZOPHRENIA: THE IMPORTANCE OF BOTH INTRINSIC AND EXTRINSIC MOTIVATION SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Reddy, Felice; Kern, Robert S.; Glynn, Shirley M.; Green, Michael F.] Greater Los Angeles VA Healthcare Syst, MIRECC, Los Angeles, CA USA. [Reddy, Felice; Kern, Robert S.; Smith, K. M.; Mitchell, Sharon; Glynn, Shirley M.; Turner, Luana R.; Zarate, Roberto; Kopelowicz, Alex; Green, Michael F.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Kopelowicz, Alex] San Fernando Valley Mental Hlth Ctr, Van Nuys, CA USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2119199 BP S187 EP S187 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200495 ER PT J AU Schlosser, D Kim, D Campellone, T Ward, C Vinogradov, S AF Schlosser, Danielle Kim, Daniel Campellone, Tim Ward, Charlie Vinogradov, Sophia TI PRIME: A NEUROSCIENCE-INFORMED MOBILE APP INTERVENTION TO TREAT REWARD PROCESSING IMPAIRMENTS AND IMPROVE QUALITY OF LIFE IN RECENT ONSET SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Schlosser, Danielle; Kim, Daniel; Campellone, Tim; Ward, Charlie; Vinogradov, Sophia] Univ Calif San Francisco, Psychiat, San Francisco, CA 94143 USA. [Vinogradov, Sophia] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [Campellone, Tim] Univ Calif Berkeley, Clin Sci, Berkeley, CA 94720 USA. NR 0 TC 1 Z9 1 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2119338 BP S332 EP S332 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200877 ER PT J AU Seidman, LJ Brent, BK Thermenos, HW Keshavan, MS Cannon, T AF Seidman, Larry J. Brent, Benjamin K. Thermenos, Heidi W. Keshavan, Matcheri S. Cannon, Tyrone TI FUNCTIONAL AND STRUCTURAL MRI STUDIES IN INDIVIDUALS WITH GENETIC OR CLINICAL HIGH RISK FOR SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Seidman, Larry J.; Brent, Benjamin K.; Thermenos, Heidi W.; Keshavan, Matcheri S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Psychiat, Boston, MA 02215 USA. [Seidman, Larry J.; Brent, Benjamin K.; Thermenos, Heidi W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat, Boston, MA USA. [Cannon, Tyrone] Yale Univ, Psychol & Psychiat, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2115562 BP S273 EP S273 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200719 ER PT J AU Seidman, LJ Shapiro, D Stone, WS Hooker, C Woodberry, KS Keshavan, MS AF Seidman, Larry J. Shapiro, Daniel Stone, William S. Hooker, Christine Woodberry, Kristen S. Keshavan, Matcheri S. TI NEUROCOGNITIVE FUNCTIONING IN CLINICAL HIGH RISK STUDIES AND IMPLICATIONS FOR COGNITIVE ENHANCEMENT IN THE PSYCHOSIS PRODROME SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Seidman, Larry J.; Stone, William S.; Woodberry, Kristen S.; Keshavan, Matcheri S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Psychiat, Boston, MA USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat, Boston, MA USA. [Shapiro, Daniel] Univ Penn, Psychiat, Philadelphia, PA 19104 USA. [Hooker, Christine] Harvard Univ, Psychol, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 BP S62 EP S62 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200167 ER PT J AU Seidman, LJ Nuechterlein, KH Gur, RC Green, MF Calkins, ME Stone, WS Lee, J Swerdlow, NR Gur, RE Braff, DL AF Seidman, Larry J. Nuechterlein, Keith H. Gur, Ruben C. Green, Michael F. Calkins, Monica E. Stone, William S. Lee, Junghee Swerdlow, Neal R. Gur, Raquel E. Braff, David L. TI NEUROCOGNITIVE ENDOPHENOTYPES IN THE COGS-2 STUDY SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Seidman, Larry J.; Stone, William S.] Harvard Univ, Sch Med, Psychiat, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Psychiat, Massachusetts Gen Hosp, Boston, MA USA. [Nuechterlein, Keith H.; Green, Michael F.; Lee, Junghee] Univ Calif Los Angeles, Geffen Sch Med, Psychiat & Biobehav Sci, Los Angeles, CA USA. [Gur, Ruben C.; Calkins, Monica E.; Gur, Raquel E.] Univ Penn, Psychiat, Philadelphia, PA 19104 USA. [Green, Michael F.; Lee, Junghee] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Swerdlow, Neal R.; Braff, David L.] Univ Calif San Diego, Psychiat, La Jolla, CA 92093 USA. [Braff, David L.] MIRECC, VISN22, VA, San Diego, CA 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 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 BP S61 EP S62 PG 2 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200166 ER PT J AU Seidman, LJ Meyer, EC Carrion, RE Cornblatt, BA Addington, J Cadenhead, KS Cannon, T McGlashan, TH Perkins, DO Tsuang, MT Walker, EF Woods, SW Heinssen, R AF Seidman, Larry J. Meyer, Eric C. Carrion, Ricardo E. Cornblatt, Barbara A. Addington, Jean Cadenhead, Kristin S. Cannon, Tyrone McGlashan, Thomas H. Perkins, Diana O. Tsuang, Ming T. Walker, Elaine F. Woods, Scott W. Heinssen, Robert TI THE RELATIONSHIP OF NEUROCOGNITION AND NEGATIVE SYMPTOMS TO SOCIAL AND ROLE FUNCTIONING OVER TIME IN INDIVIDUALS AT CLINICAL HIGH RISK SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Meyer, Eric C.] VA VISN 17 Ctr Excellence Res Returning War Vet, Waco, TX USA. [Meyer, Eric C.] Texas A&M Hlth Sci Ctr, Psychiat & Behav Sci, Coll Med, College Stn, TX USA. [Carrion, Ricardo E.; Cornblatt, Barbara A.] NS LIJHS, Zucker Hillside Hosp, Div Psychiat Res, Glen Oaks, NY USA. [Addington, Jean] Univ Calgary, Psychiat, Calgary, AB, Canada. [Cadenhead, Kristin S.; Tsuang, Ming T.] Univ Calif San Diego, Psychiat, San Diego, CA USA. [Cannon, Tyrone] Univ Calif Los Angeles, Psychol & Psychiat & Biobehav Sci, Los Angeles, CA USA. [Cannon, Tyrone; McGlashan, Thomas H.; Woods, Scott W.] Yale Univ, Psychiat, New Haven, CT USA. [Perkins, Diana O.] Univ N Carolina, Psychiat, Chapel Hill, NC USA. [Tsuang, Ming T.] UCSD, Ctr Behav Genom, La Jolla, CA USA. [Tsuang, Ming T.] UCSD, Inst Genom Med, La Jolla, CA USA. [Walker, Elaine F.] Emory Univ, Psychol & Psychiat, Atlanta, GA 30322 USA. [Heinssen, Robert] NIMH, Schizophrenia Spectrum Res Program, Div Adult Translat Res, Bethesda, MD 20892 USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Psychiat, Boston, MA USA. [Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 BP S61 EP S61 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200165 ER PT J AU Siever, LJ AF Siever, Larry J. TI SOCIAL COGNITION IN THE SCHIZOPHRENIA SPECTRUM SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Siever, Larry J.] Icahn Sch Med Mt Sinai, Psychiat, New York, NY 10029 USA. [Siever, Larry J.] James J Peters VAMC, VISN MIRECC 3, Bronx, NY USA. 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 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2112833 BP S190 EP S190 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200502 ER PT J AU Spencer, KM AF Spencer, Kevin M. TI EVOKED AND SPONTANEOUS GAMMA ABNORMALITIES IN SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Spencer, Kevin M.] VA Boston Healthcare Syst, Res Serv, Boston, MA USA. [Spencer, Kevin M.] Harvard Univ, Sch Med, Psychiat, 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 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2118703 BP S26 EP S26 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200069 ER PT J AU Tabak, NT Horan, WP Bender, A Dolinsky, M Green, MF AF Tabak, Naomi Tuchman Horan, William Powers Bender, A. Dolinsky, M. Green, Michael F. TI MINDFULNESS, EMOTION REGULATION, AND NEGATIVE SYMPTOMS IN SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Tabak, Naomi Tuchman] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Tabak, Naomi Tuchman; Horan, William Powers; Bender, A.; Dolinsky, M.; Green, Michael F.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Horan, William Powers; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2081514 BP S192 EP S193 PG 2 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200509 ER PT J AU Walsh-Messinger, J Keller, A Cieslak, K Rotondo, E Goetz, R Gonen, O Malaspina, D AF Walsh-Messinger, Julie Keller, Andreas Cieslak, Kristina Rotondo, Elena Goetz, Raymond Gonen, Oded Malaspina, Dolores TI INFLAMMATION IN THE ANTERIOR CINGULATE CORTEX (ACC) AND ASSOCIATIONS WITH OLFACTORY HEDONICS AND ANHEDONIA IN SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Walsh-Messinger, Julie] Icahn Sch Med Mt Sinai, Psychiat, New York, NY 10029 USA. [Walsh-Messinger, Julie] James J Peters VA Med Ctr, Mental Illness Educ Res & Clin Ctr, Bronx, NY USA. [Keller, Andreas; Cieslak, Kristina; Rotondo, Elena; Goetz, Raymond; Malaspina, Dolores] NYU, Sch Med, Inst Social & Psychiat Initiat InSPIRES, Psychiat, New York, NY USA. [Keller, Andreas] Rockefeller Univ, New York, NY 10021 USA. [Goetz, Raymond] Columbia Univ, Psychiat, New York, NY USA. [Gonen, Oded] NYU, Sch Med, Radiol, New York, NY USA. [Malaspina, Dolores] NY State Off Mental Hlth, Creedmor Psychiat Ctr, Queens, 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 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2083528 BP S278 EP S279 PG 2 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200733 ER PT J AU Wu, WL Adams, CE Stevens, K Chow, K Patterson, PH AF Wu, Wei-Li Adams, C. E. Stevens, Karen Chow, K. Patterson, P. H. TI NICOTINIC CHOLINERGIC MODULATION OF THE FETAL BRAIN RESPONSE TO MATERNAL IMMUNE ACTIVATION SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Wu, Wei-Li; Chow, K.; Patterson, P. H.] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA. [Adams, C. E.] Denver VA Med Ctr, Denver, CO USA. [Adams, C. E.; Stevens, Karen] Univ Colorado Denver, Dept Psychiat, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2077235 BP S216 EP S216 PG 1 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200573 ER PT J AU Yao, JK Leonard, S Reddy, R AF Yao, Jeffrey K. Leonard, Sherry Reddy, Ravinder TI HOMEOSTATIC IMBALANCE OF PURINE CATABOLISM IN SCHIZOPHRENIA POSTMORTEM BRAIN SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 15th International Congress on Schizophrenia Research (ICOSR) CY MAR 28-APR 01, 2015 CL Colorado Springs, CO C1 [Yao, Jeffrey K.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Yao, Jeffrey K.] VA Pittsburgh Healthcare Syst, MIRECC VISN4, Pittsburgh, PA USA. [Yao, Jeffrey K.; Reddy, Ravinder] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Yao, Jeffrey K.; Reddy, Ravinder] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA USA. [Leonard, Sherry] Univ Colorado, Dept Psychiat, Denver, CO 80202 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 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2015 VL 41 SU 1 MA 2118353 BP S297 EP S298 PG 2 WC Psychiatry SC Psychiatry GA CG8HO UT WOS:000353548200784 ER PT J AU Diep, CQ Peng, ZZ Ukah, TK Kelly, PM Daigle, RV Davidson, AJ AF Diep, Cuong Q. Peng, Zhenzhen Ukah, Tobechukwu K. Kelly, Paul M. Daigle, Renee V. Davidson, Alan J. TI Development of the Zebrafish Mesonephros SO GENESIS LA English DT Article DE kidney; pronephros; nephron ID KIDNEY DEVELOPMENT; NEPHRON SEGMENTATION; PRONEPHROS; EXPRESSION; GENES; IDENTIFICATION; REGENERATION; LIM1; WT1A AB The vertebrate kidney plays an essential role in removing metabolic waste and balancing water and salt. This is carried out by nephrons, which comprise a blood filter attached to an epithelial tubule with proximal and distal segments. In zebrafish, two nephrons are first formed as part of the embryonic kidney (pronephros) and hundreds are formed later to make up the adult kidney (mesonephros). Previous studies have focused on the development of the pronephros while considerably less is known about how the mesonephros is formed. Here, we characterize mesonephros development in zebrafish and examine the nephrons that form during larval metamorphosis. These nephrons, arising from proliferating progenitor cells that express the renal transcription factor genes wt1b, pax2a, and lhx1a, form on top of the pronephric tubules and develop a segmentation pattern similar to pronephric nephrons. We find that the pronephros acts as a scaffold for the mesonephros, where new nephrons fuse with the distal segments of the pronephric tubules to form the final branching network that characterizes the adult zebrafish kidney. genesis 53:257-269, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Diep, Cuong Q.; Daigle, Renee V.; Davidson, Alan J.] Massachusetts Gen Hosp, Dept Med, Ctr Regenerat Med, Boston, MA 02114 USA. [Diep, Cuong Q.; Davidson, Alan J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Diep, Cuong Q.; Davidson, Alan J.] Harvard Stem Cell Inst, Kidney Program, Cambridge, MA USA. [Diep, Cuong Q.; Ukah, Tobechukwu K.; Kelly, Paul M.] Indiana Univ Penn, Dept Biol, Indiana, PA 15705 USA. [Peng, Zhenzhen; Davidson, Alan J.] Univ Auckland, Dept Mol Med & Pathol, Auckland 1142, New Zealand. RP Davidson, AJ (reprint author), Univ Auckland, Dept Mol Med & Pathol, Sch Med Sci, Private Bag 92019, Auckland 1142, New Zealand. EM a.davidson@auckland.ac.nz FU Health Research Council (HRC), New Zealand; Harvard Stem Cell Institute; American Society of Nephrology; National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [DK069403-06]; Massachusetts General Hospital; Indiana University of Pennsylvania; Commonwealth of Pennsylvania University Biologists FX Contract grant sponsor: Health Research Council (HRC), New Zealand; Contract grant sponsor: Harvard Stem Cell Institute; Contract grant sponsor: American Society of Nephrology; Contract grant sponsor: National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases, Contract grant number(s): DK069403-06; Contract grant sponsor: Massachusetts General Hospital (Fund for Medical Discovery); Contract grant sponsor: Indiana University of Pennsylvania (Startup Fund, USRC Small Grant, President's Advancing Grantsmanship Awards, the President's Strategic Initiative Fund, and the Professional Development Fund); Contract grant sponsor: Commonwealth of Pennsylvania University Biologists. NR 25 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-954X EI 1526-968X J9 GENESIS JI Genesis PD MAR-APR PY 2015 VL 53 IS 3-4 BP 257 EP 269 DI 10.1002/dvg.22846 PG 13 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA CH3JC UT WOS:000353926000001 PM 25677367 ER PT J AU Fourman, LT Fazeli, PK AF Fourman, Lindsay T. Fazeli, Pouneh K. TI Neuroendocrine Causes of Amenorrhea-An Update SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID GONADOTROPIN-RELEASING-HORMONE; CONGENITAL ADRENAL-HYPERPLASIA; STEROID 21-HYDROXYLASE DEFICIENCY; FUNCTIONAL HYPOTHALAMIC AMENORRHEA; SHEEHANS-SYNDROME; SERUM PROLACTIN; PITUITARY DYSFUNCTION; LUTEINIZING-HORMONE; KALLMANN-SYNDROME; IDIOPATHIC HYPERPROLACTINEMIA AB Context: Secondary amenorrhea-the absence of menses for three consecutive cycles-affects approximately 3-4% of reproductive age women, and infertility-the failure to conceive after 12 months of regular intercourse-affects approximately 6-10%. Neuroendocrine causes of amenorrhea and infertility, including functional hypothalamic amenorrhea and hyperprolactinemia, constitute a majority of these cases. Objective: In this review, we discuss the physiologic, pathologic, and iatrogenic causes of amenorrhea and infertility arising from perturbations in the hypothalamic-pituitary-adrenal axis, including potential genetic causes. We focus extensively on the hormonal mechanisms involved in disrupting the hypothalamic-pituitary-ovarian axis. Conclusions: A thorough understanding of the neuroendocrine causes of amenorrhea and infertility is critical for properly assessing patients presenting with these complaints. Prompt evaluation and treatment are essential to prevent loss of bone mass due to hypoestrogenemia and/or to achieve the time-sensitive treatment goal of conception. C1 [Fourman, Lindsay T.; Fazeli, Pouneh K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Fazeli, Pouneh K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Fazeli, PK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM pkfazeli@partners.org FU National Institutes of Health [K23-DK094820]; Claflin Distinguished Scholar Award FX This project was supported by National Institutes of Health grant K23-DK094820 (to P.K.F.) and the Claflin Distinguished Scholar Award (to P.K.F.). NR 129 TC 7 Z9 9 U1 2 U2 9 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2015 VL 100 IS 3 BP 812 EP 824 DI 10.1210/jc.2014-3344 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG5TR UT WOS:000353358900028 PM 25581597 ER PT J AU McAninch, EA Jo, S Preite, NZ Farkas, E Mohacsik, P Fekete, C Egri, P Gereben, B Li, Y Deng, YP Patti, ME Zevenbergen, C Peeters, RP Mash, DC Bianco, AC AF McAninch, Elizabeth A. Jo, Sungro Preite, Nailliw Z. Farkas, Erzsebet Mohacsik, Petra Fekete, Csaba Egri, Peter Gereben, Balazs Li, Yan Deng, Youping Patti, Mary-Elizabeth Zevenbergen, Chantal Peeters, Robin P. Mash, Deborah C. Bianco, Antonio C. TI Prevalent Polymorphism in Thyroid Hormone-Activating Enzyme Leaves a Genetic Fingerprint That Underlies Associated Clinical Syndromes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; TYPE-2 DEIODINASE; THR92ALA POLYMORPHISM; HUNTINGTONS-DISEASE; DIO2 GENE; EXPRESSION; THYROXINE; STRESS; CELLS; PATHWAYS AB Context: A common polymorphism in the gene encoding the activating deiodinase (Thr92Ala-D2) is known to be associated with quality of life in millions of patients with hypothyroidism and with several organ-specific conditions. This polymorphism results in a single amino acid change within the D2 molecule where its susceptibility to ubiquitination and proteasomal degradation is regulated. Objective: To define the molecular mechanisms underlying associated conditions in carriers of the Thr92Ala-D2 polymorphism. Design, Setting, Patients: Microarray analyses of 19 postmortem human cerebral cortex samples were performed to establish a foundation for molecular studies via a cell model of HEK-293 cells stably expressing Thr92 or Ala92 D2. Results: The cerebral cortex of Thr92Ala-D2 carriers exhibits a transcriptional fingerprint that includes sets of genes involved in CNS diseases, ubiquitin, mitochondrial dysfunction (chromosomal genes encoding mitochondrial proteins), inflammation, apoptosis, DNA repair, and growth factor signaling. Similar findings were made in Ala92-D2-expressing HEK-293 cells and in both cases there was no evidence that thyroid hormone signaling was affected ie, the expression level of T3-responsive genes was unchanged, but that several other genes were differentially regulated. The combined microarray analyses (brain/cells) led to the development of an 81-gene classifier that correctly predicts the genotype of homozygous brain samples. In contrast to Thr92-D2, Ala92-D2 exhibits longer half-life and was consistently found in the Golgi. A number of Golgi-related genes were down-regulated in Ala92-D2-expressing cells, but were normalized after 24-h-treatment with the antioxidant N-acetylecysteine. Conclusions: Ala92-D2 accumulates in the Golgi, where its presence and/or ensuing oxidative stress disrupts basic cellular functions and increases pre-apoptosis. These findings are reminiscent to disease mechanisms observed in other neurodegenerative disorders such as Huntington's disease, and could contribute to the unresolved neurocognitive symptoms of affected carriers. C1 [McAninch, Elizabeth A.; Jo, Sungro; Preite, Nailliw Z.; Bianco, Antonio C.] Rush Univ, Div Endocrinol & Metab, Med Ctr, Chicago, IL 60612 USA. [Farkas, Erzsebet; Mohacsik, Petra; Fekete, Csaba; Egri, Peter; Gereben, Balazs] Hungarian Acad Sci, Dept Endocrine Neurobiol, Inst Expt Med, H-1083 Budapest, Hungary. [Farkas, Erzsebet] Peter Pazmany Catholic Univ, Multidisciplinary Doctoral Sch Sci & Technol, H-1083 Budapest, Hungary. [Mohacsik, Petra; Egri, Peter] Semmelweis Univ, Janos Szentagothai PhD Sch Neurosci, H-1085 Budapest, Hungary. [Fekete, Csaba] Tufts Med Ctr,Boston, Div Endocrinol, Diabet & Metab, Boston, MA 02111 USA. [Li, Yan; Deng, Youping] Rush Univ, Dept Med, Med Ctr, Chicago, IL 60612 USA. [Patti, Mary-Elizabeth] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [Zevenbergen, Chantal; Peeters, Robin P.] Erasmus MC, Div Endocrinol, RotterdamThyroid Ctr, Dept Internal Med, Rotterdam, Netherlands. [Mash, Deborah C.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. RP Bianco, AC (reprint author), Rush Univ, Div Endocrinol & Metab, Med Ctr, 1735 W Harrison St,212 Cohn Bldg, Chicago, IL 60612 USA. EM abianco@deiodinase.org RI Peeters, Robin/P-3603-2014; OI Fekete, Csaba/0000-0002-8206-562X FU National Institute of Diabetes and Digestive Kidney Diseases [DK58538]; Hungarian Brain Research Program; Hungarian Academy of Sciences; NIMH; NINDS; NICHD; National Institutes of Health, Department of Health and Human Services [HHSN271201300028C] FX This work was supported by grants from the National Institute of Diabetes and Digestive Kidney Diseases (DK58538), the Hungarian Brain Research Program, and the Lendulet grant of the Hungarian Academy of Sciences. The University of Miami Brain Endowment Bank is funded in part with Federal funds from the NIMH, NINDS, and NICHD, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN271201300028C. NR 46 TC 12 Z9 12 U1 0 U2 15 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2015 VL 100 IS 3 BP 920 EP 933 DI 10.1210/jc.2014-4092 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG5TR UT WOS:000353358900040 PM 25569702 ER PT J AU Shaw, ND Butler, JP Nemati, S Kangarloo, T Ghassemi, M Malhotra, A Hall, JE AF Shaw, N. D. Butler, J. P. Nemati, S. Kangarloo, T. Ghassemi, M. Malhotra, A. Hall, J. E. TI Accumulated Deep Sleep Is a Powerful Predictor of LH Pulse Onset in Pubertal Children SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; LUTEINIZING-HORMONE; APNEA SYNDROME; SECRETION; NEURONS; GIRLS; ACTIVATION; PULSATILE; NUCLEUS; ADENOTONSILLECTOMY AB Context: During puberty, reactivation of the reproductive axis occurs during sleep, with LH pulses specifically tied to deep sleep. This association suggests that deep sleep may stimulate LH secretion, but there have been no interventional studies to determine the characteristics of deep sleep required for LH pulse initiation. Objective: The objective of this study was to determine the effect of deep sleep fragmentation on LH secretion in pubertal children. Design and Setting: Studies were performed in a clinical research center. Subjects: Fourteen healthy pubertal children (11.3-14.1 y) participated in the study. Interventions: Subjects were randomized to two overnight studies with polysomnography and frequent blood sampling, with or without deep sleep disruption via auditory stimuli. Results: An average of 68.1 +/- 10.7 (+/- SE) auditory stimuli were delivered to interrupt deep sleep during the disruption night, limiting deep sleep to only brief episodes (average length disrupted 1.3 +/- 0.2 min vs normal 7.1 +/- 0.8 min, P < .001), and increasing the number of transitions between non-rapid eye movement (NREM), REM, and wake (disrupted 274.5 +/- 33.4 vs normal 131.2 +/- 8.1, P = .001). There were no differences in mean LH (normal: 3.2 +/- 0.4 vs disrupted: 3.2 +/- 0.5 IU/L), LH pulse frequency (0.6 +/- 0.06 vs 0.6 +/- 0.07 pulses/h), or LH pulse amplitude (2.8 +/- 0.4 vs 2.8 +/- 0.4 IU/L) between the two nights. Poisson process modeling demonstrated that the accumulation of deep sleep in the 20 minutes before an LH pulse, whether consolidated or fragmented, was a significant predictor of LH pulse onset (P < .001). Conclusion: In pubertal children, nocturnal LH augmentation and pulse patterning are resistant to deep sleep fragmentation. These data suggest that, even when fragmented, deep sleep is strongly related to activation of the GnRH pulse generator. C1 [Shaw, N. D.; Kangarloo, T.; Hall, J. E.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Shaw, N. D.; Hall, J. E.] Harvard Univ, Sch Med, Div Endocrinol, Childrens Hosp Boston,Div Sleep Med, Cambridge, MA 02138 USA. [Butler, J. P.] Harvard Univ, Sch Med, Div Sleep & Circadian Disorders, Brigham & Womens Hosp, Boston, MA 02115 USA. [Butler, J. P.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Nemati, S.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Ghassemi, M.] MIT, Elect Engn & Comp Sci, Cambridge, MA 02142 USA. [Malhotra, A.] Univ Calif San Diego, Div Pulm & Crit Care Med, La Jolla, CA 92093 USA. RP Shaw, ND (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX 5,55 Fruit St, Boston, MA 02114 USA. EM nshaw@partners.org OI Shaw, Natalie/0000-0002-0847-9170; Hall, Janet/0000-0003-4644-3061 FU National Institutes of Health [K23HD073304-02, K24HL093218]; Pediatric Endocrine Society; Harvard University [1UL1TR001102-01] FX N.D.S. received fellowship support from the National Institutes of Health (Grant K23HD073304-02), the Pediatric Endocrine Society, and Harvard Catalyst [The Harvard Clinical and Translational Science Center (Award 1UL1TR001102-01)] and financial contributions from Harvard University and its affiliated academic health care centers. A.M. is funded by the National Institutes of Health (Grant K24HL093218). NR 39 TC 1 Z9 1 U1 1 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2015 VL 100 IS 3 BP 1062 EP 1070 DI 10.1210/jc.2014-3563 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG5TR UT WOS:000353358900056 PM 25490277 ER PT J AU Balasubramanian, R Chew, S MacKinnon, SE Kang, PB Andrews, C Chan, WM Engle, EC AF Balasubramanian, Ravikumar Chew, Sheena MacKinnon, Sarah E. Kang, Peter B. Andrews, Caroline Chan, Wai-Man Engle, Elizabeth C. TI Expanding the Phenotypic Spectrum and Variability of Endocrine Abnormalities Associated With TUBB3 E410K Syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; KALLMANN-SYNDROME; DEFICIENCY; MUTATIONS AB Context: A heterozygous de novo c.1228G>A mutation (E410K) in the TUBB3 gene encoding the neuronal-specific beta-tubulin isotype 3 (TUBB3) causes the TUBB3 E410K syndrome characterized by congenital fibrosis of the extraocular muscles (CFEOM), facial weakness, intellectual and social disabilities, and Kallmann syndrome (anosmia with hypogonadotropic hypogonadism). All TUBB3 E410K subjects reported to date are sporadic cases. Objective: This study aimed to report the clinical, genetic, and molecular features of a familial presentation of the TUBB3 E410K syndrome. Design: Case report of a mother and three affected children with clinical features of the TUBB3 E410K syndrome. Setting: Academic Medical Center. Main Outcome Measures: Genetic analysis of the TUBB3 gene and clinical evaluation of endocrine and nonendocrine phenotypes. Results: A de novo TUBB3 c.1228G>A mutation arose in a female proband who displayed CFEOM, facial weakness, intellectual and social disabilities, and anosmia. However, she underwent normal sexual development at puberty and had three spontaneous pregnancies with subsequent autosomal- dominant inheritance of the mutation by her three boys. All sons displayed nonendocrine features of the TUBB3 E410K syndrome similar to their mother but, in addition, had variable features suggestive of additional endocrine abnormalities. Conclusions: This first report of an autosomal-dominant inheritance of the TUBB3 c.1228G>A mutation in a family provides new insights into the spectrum and variability of endocrine phenotypes associated with the TUBB3 E410K syndrome. These observations emphasize the need for appropriate clinical evaluation and complicate genetic counseling of patientsandfamilies with this syndrome. C1 [Balasubramanian, Ravikumar] Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. [Balasubramanian, Ravikumar] Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Balasubramanian, Ravikumar; Chew, Sheena; Kang, Peter B.; Andrews, Caroline; Chan, Wai-Man; Engle, Elizabeth C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chew, Sheena; Kang, Peter B.; Andrews, Caroline; Chan, Wai-Man; Engle, Elizabeth C.] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Chew, Sheena; Andrews, Caroline; Chan, Wai-Man; Engle, Elizabeth C.] Boston Childrens Hosp, Kirby Neurobiol Ctr, Boston, MA 02115 USA. [MacKinnon, Sarah E.; Engle, Elizabeth C.] Boston Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA. [Chew, Sheena; Andrews, Caroline; Chan, Wai-Man; Engle, Elizabeth C.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Engle, EC (reprint author), Boston Childrens Hosp, CLS14075,300 Longwood Ave, Boston, MA 02115 USA. EM elizabeth.engle@childrens.harvard.edu FU National Eye Institute of the National Institutes of Health [R01EY12498]; Boston Children's Hospital Intellectual and Developmental Disabilities Research Center [HD018655]; Children's Hospital Ophthalmology Foundation; National Institute of Child Health and Development [K23HD077043]; HHMI Medical Fellowship; Harvard Medical School FX This work was supported by the National Eye Institute of the National Institutes of Health (R01EY12498 to E.C.E.), the Boston Children's Hospital Intellectual and Developmental Disabilities Research Center (HD018655), and the Children's Hospital Ophthalmology Foundation (E.C.E., S.M.). R.B. is supported by a Career Development Grant from the National Institute of Child Health and Development (K23HD077043). S.C. was funded by an HHMI Medical Fellowship and Harvard Medical School. E.C.E. is a Howard Hughes Medical Institute Investigator. NR 12 TC 2 Z9 2 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2015 VL 100 IS 3 BP E473 EP E477 DI 10.1210/jc.2014-4107 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG5TR UT WOS:000353358900014 PM 25559402 ER PT J AU Huh, JY Siopi, A Mougios, V Park, KH Mantzoros, CS AF Huh, Joo Young Siopi, Aikaterina Mougios, Vassilis Park, Kyung Hee Mantzoros, Christos S. TI Irisin in Response to Exercise in Humans With and Without Metabolic Syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SKELETAL-MUSCLE; CELL-PROLIFERATION; MESSENGER-RNA; FNDC5; PROTEIN; SERUM; LINES; FAT; MEN AB Context: Irisin is a recently identified exercise-induced myokine. However, the circulating levels of irisin in response to different types of exercise in subjects with metabolic syndrome are unknown. Objective: This study aimed to study the levels of irisin in healthy males and subjects with metabolic syndrome at baseline and in response to exercise. Design: Each individual completed high-intensity interval exercise (HIIE), continuous moderate-intensity exercise (CME), and resistance exercise (RE) sessions in a random, crossover design. Percentage change in circulating irisin levels was examined. Two different irisin assays were used to compare the results of the RE study. Results: Circulating irisin increased immediately after HIIE, CME, and RE and declined 1 hour later. The increase was greater in response to resistance compared with either high-intensity intermittent exercise or CME. Change in irisin in response to exercise did not differ between individuals with and without metabolic syndrome. Conclusions: Exercise is able to increase circulating irisin levels in individuals with the metabolic syndrome as well as healthy individuals. Whether this increase may contribute to the beneficial effects of exercise on patients with the metabolic syndrome remains to be studied further. C1 [Huh, Joo Young; Park, Kyung Hee; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Siopi, Aikaterina; Mougios, Vassilis] Aristotle Univ Thessaloniki, Sch Phys Educ & Sports Sci, Thessaloniki 54124, Greece. [Park, Kyung Hee] Hallym Univ, Sacred Heart Hosp, Dept Family Med, Gyeonggi Do 431796, South Korea. [Mantzoros, Christos S.] Harvard Univ, Boston VA Healthcare Syst, Sch Med, Endocrinol Sect, Boston, MA USA. RP Mantzoros, CS (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, 330 Brookline Ave,Feldberg 876, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu OI Park, Kyung Hee/0000-0001-9806-0076 FU Clinical Science Research and Development Service of the VA Office of Research and Development; Greek State Scholarship Foundation FX This work was supported by an award from the Clinical Science Research and Development Service of the VA Office of Research and Development. Part of this work was supported by a fellowship of the Greek State Scholarship Foundation to A.S. under the program, "IKY Fellowships of Excellence for Postgraduate Studies in Greece-SIEMENS Program." NR 22 TC 15 Z9 17 U1 1 U2 9 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2015 VL 100 IS 3 BP E453 EP E457 DI 10.1210/jc.2014-2416 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG5TR UT WOS:000353358900010 PM 25514098 ER PT J AU Arya, R White, K AF Arya, Richa White, Kristin TI Cell death in development: Signaling pathways and core mechanisms SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE Cell death; Drosophila; Development; Hox; Notch; Ras ID CENTRAL-NERVOUS-SYSTEM; DEVELOPING DROSOPHILA RETINA; EMBRYONIC PATTERN REPAIR; ANIMAL DEVELOPMENT; EGF RECEPTOR; POSTEMBRYONIC DEVELOPMENT; CRANIOFACIAL DEVELOPMENT; CAENORHABDITIS-ELEGANS; TRANSCRIPTION FACTORS; MAMMALIAN DEVELOPMENT AB Programmed cell death eliminates unneeded and dangerous cells in a timely and effective manner during development. In this review, we examine the role cell death plays during development in worms, flies and mammals. We discuss signaling pathways that regulate developmental cell death, and describe how they communicate with the core cell death pathways. In most organisms, the majority of developmental cell death is seen in the nervous system. Therefore we focus on what is known about the regulation of developmental cell death in this tissue. Understanding how the cell death is regulated during development may provide insight into how this process can be manipulated in the treatment of disease. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Arya, Richa; White, Kristin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, CBRC, Boston, MA 02129 USA. RP White, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, CBRC, Boston, MA 02129 USA. EM kristin.white@cbrc2.mgh.harvard.edu FU MGH Fund for Medical Discovery [R01GM55568, R01GM110477] FX We would like to acknowledge funding from the MGH Fund for Medical Discovery (R.A.) and R01GM55568 and R01GM110477 (K.W.). Tatevik Sarkissian and Ritu Tomar provided important comments on the manuscript. NR 158 TC 9 Z9 10 U1 5 U2 17 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD MAR PY 2015 VL 39 BP 12 EP 19 DI 10.1016/j.semcdb.2015.02.001 PG 8 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA CG5MW UT WOS:000353337000003 PM 25668151 ER PT J AU Kendall, RE Gosser, RA Schulz, LT Trapskin, PJ Caponi, B Safdar, N AF Kendall, Ronald E. Gosser, Rena A. Schulz, Lucas T. Trapskin, Philip J. Caponi, Bartho Safdar, Nasia TI Anti-diarrheat medication use in the treatment of Ebola virus-induced diarrhea SO TRAVEL MEDICINE AND INFECTIOUS DISEASE LA English DT Letter DE Ebola; Anti-diarrheals; Supportive care; Viral gastroenteritis ID MANAGEMENT C1 [Kendall, Ronald E.; Gosser, Rena A.; Schulz, Lucas T.; Trapskin, Philip J.] Univ Wisconsin Hosp & Clin, Dept Pharm, Madison, WI 53705 USA. [Caponi, Bartho] Univ Wisconsin, Div Hosp Med, Dept Med, Sch Med & Publ Hlth, Madison, WI 53705 USA. [Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. [Safdar, Nasia] Univ Wisconsin, Div Infect Dis, Dept Med, Sch Med & Publ Hlth, Madison, WI 53705 USA. RP Kendall, RE (reprint author), 600 Highland Ave F6-133, Madison, WI 53792 USA. EM rkendall@uwhealth.org; rgosser@uwhealth.org NR 6 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1477-8939 EI 1873-0442 J9 TRAVEL MED INFECT DI JI Travel Med. Infect. Dis. PD MAR-APR PY 2015 VL 13 IS 2 BP 205 EP 206 DI 10.1016/j.tmaid.2015.01.003 PG 2 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA CH0VT UT WOS:000353741200019 PM 25682446 ER PT J AU Pham, A Hariri, S Yusin, J AF Pham, A. Hariri, S. Yusin, J. TI Timing isn't everything: A case of recurrent angio-oedema SO ALLERGOLOGIA ET IMMUNOPATHOLOGIA LA English DT Letter ID CONVERTING ENZYME-INHIBITORS C1 [Pham, A.; Hariri, S.; Yusin, J.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Pham, A (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. EM Andrewqpham@gmail.conn; Sherwinucla@yahoo.com; Joseph.Yusin2@va.gov NR 10 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER DOYMA SL PI BARCELONA PA TRAVESERA DE GARCIA, 17-21, BARCELONA, 08021, SPAIN SN 0301-0546 EI 1578-1267 J9 ALLERGOL IMMUNOPATH JI Allergol. Immunopath. PD MAR-APR PY 2015 VL 43 IS 2 BP 230 EP 231 DI 10.1016/j.aller.2014.02.001 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA CF7OO UT WOS:000352746400022 PM 24948189 ER PT J AU Wilens, T Zulauf, C Ryland, D Carrellas, N Catalina-Wellington, I AF Wilens, Timothy Zulauf, Courtney Ryland, Denece Carrellas, Nicholas Catalina-Wellington, Isela TI Prescription Medication Misuse Among Opioid Dependent Patients Seeking Inpatient Detoxification SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID NONMEDICAL USE; CHRONIC PAIN; CLONIDINE; DISORDER; BUPRENORPHINE; PREVALENCE; PREDICTORS; ANALGESIA; MORTALITY; METHADONE AB Background and ObjectivesOpioid related morbidity and mortality is heightened in context to the concomitant use of psychotropic medications. The aim of this project was to examine the extent to which opioid dependent patients seeking detoxification are using and misusing specific psychotropic agents. MethodsAs part of a quality assurance/improvement project, we systematically assessed prospectively consecutive admissions to a public detoxification program using a self-report questionnaire to query for specific psychotropic medication use. Patients were asked about having a current prescription, appropriate use, and/or medical misuse (higher doses, using without prescription) of amphetamine salts, clonazepam, clonidine, gabapentin, and pregabalin. ResultsWe had data on 196 admissions including 162 patients with opioid dependency. Patients receiving detoxification from opioids compared to alcohol had statistically significant higher rates of medication misuse (30% vs. 0%, respectively; (2)=12.8, p<.0003). Of opioid dependent patients receiving prescription medication, 28% reported using higher amounts of each medication than prescribed. Of opioid patients, 10% self-reported misusing clonidine, 22% gabapentin, 7% pregabalin, 25% clonazepam, 11% amphetamine salts, and 36% any of these medications. Discussion and ConclusionsDespite the nonaddictive nature of some medications (eg, gabapentin, clonidine), high rates of medication misuse in opioid dependent patients admitted for detoxification was found and appeared similar to rates of misuse among controlled substances such as clonazepam and amphetamine salts. These data suggest that opioid dependent patients should be queried for the appropriate use of prescribed medications and that practitioners need to monitor for medication misuse in opioid dependent patients. (Am J Addict 2015;24:173-177) C1 [Wilens, Timothy; Zulauf, Courtney; Carrellas, Nicholas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Wilens, Timothy; Ryland, Denece; Catalina-Wellington, Isela] Andrew House Detoxificat Ctr, Bay Cove Human Serv, Quincy, MA USA. RP Wilens, T (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol, 55 Fruit St,YAW 6A, Boston, MA 02114 USA. EM twilens@partners.org FU National Institute on Drug Abuse (NIDA); Euthymics; Shire; Theravance; TRIS FX Over the past three years Timothy Wilens receives/d research support from, or is/has been on the advisory board for the following Pharmaceutical Companies: National Institute on Drug Abuse (NIDA), Euthymics, Shire, Theravance, and TRIS. Dr. Timothy Wilens is or has been a consultant for: Bay Cove Human Services, Euthymics, Major and Minor League Baseball, the National Football League (ERM Associates), Shire, and TRIS. Dr. Timothy Wilens has a published book with Guilford Press. Straight Talk About Psychiatric Medications for Kids. NR 30 TC 7 Z9 8 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD MAR PY 2015 VL 24 IS 2 BP 173 EP 177 DI 10.1111/ajad.12159 PG 5 WC Substance Abuse SC Substance Abuse GA CF8KI UT WOS:000352807600012 PM 25864607 ER PT J AU Wang, EA McGinnis, KA Long, JB Akgun, KM Edelman, EJ Rimland, D Wang, KH Justice, AC Fiellin, DA AF Wang, Emily A. McGinnis, Kathleen A. Long, Jessica B. Akguen, Kathleen M. Edelman, E. Jennifer Rimland, David Wang, Karen H. Justice, Amy C. Fiellin, David A. TI Incarceration and Health Outcomes in HIV-Infected Patients: The Impact of Substance Use, Primary Care Engagement, and Antiretroviral Adherence SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID INJECTION-DRUG USERS; ALCOHOL-USE; HIGH-RISK; VETERANS; THERAPY; RELEASE; PRISON; ACCESS; DEATH; MEN AB Background and ObjectivesOne in seven HIV-infected individuals is incarcerated each year. We used data from the Veterans Aging Cohort Study (VACS) to explore the relationship between incarceration and HIV disease outcomes and evaluate potential mediators of this relationship. MethodsHIV disease outcomes included: low CD4 counts (<200 cells/mL), detectable viral RNA loads (>500 copies/mL), and the VACS Index score. We performed a mediation analysis among 1,591 HIV-infected patients to examine whether unhealthy alcohol use, drug use, primary care engagement, or antiretroviral adherence mediated observed associations. ResultsAmong 1,591 HIV-infected patients, 47% reported having a history of incarceration. In multivariate analyses, a history of incarceration was associated with a higher VACS Index score ( 2.47, 95% CI 0.52-4.43). Mediation analysis revealed that recent drug use attenuated the association by 22% ( 1.93, 95% CI -0.06, 3.91) while other proposed mediators did not. Conclusions and Scientific SignificanceImproving access to drug treatment when incarcerated and upon release may be an important target to improving the health of HIV-infected individuals with a history of incarceration. (Am J Addict 2015;24:178-184) C1 [Wang, Emily A.; Long, Jessica B.; Akguen, Kathleen M.; Edelman, E. Jennifer; Wang, Karen H.; Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Med, New Haven, CT 06510 USA. [Wang, Emily A.; Edelman, E. Jennifer; Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Publ Hlth, Ctr Interdisciplinary Res AIDS, New Haven, CT 06510 USA. [McGinnis, Kathleen A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Akguen, Kathleen M.; Wang, Karen H.; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Rimland, David] Atlanta VA Med Ctr, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. RP Wang, EA (reprint author), Yale Univ, Sch Med, Gen Internal Med, Harkness Hall Bldg A,367 Cedar St,Suite 410A, New Haven, CT 06510 USA. EM emily.wang@yale.edu OI Fiellin, David/0000-0002-4006-010X; Justice, Amy/0000-0003-0139-5502 FU National Institute on Drug Abuse [1R03DA031592]; National Institute on Alcohol Abuse and Alcoholism [U01 AA 13566, U10 AA 13566]; National Institute of Aging (NIA) [K23 AG00826]; Robert Wood Johnson Generalist Faculty Scholar Award; NIA; National Institute of Mental Health; VA HSR&D Research Enhancement Award Program (REAP) PRIME Project [REA 08-266]; National Heart Lung Blood Institute [K23 HL103720]; Yale Clinical Center of Investigation's CTSA [UL1 RR024139] FX Funding for this study was provided by National Institute on Drug Abuse (1R03DA031592) to Dr. Wang; the NIDA had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. VACS is funded by the National Institute on Alcohol Abuse and Alcoholism (U01 AA 13566 and U10 AA 13566), National Institute of Aging (NIA, K23 AG00826), Robert Wood Johnson Generalist Faculty Scholar Award, an Inter-agency Agreement between NIA, National Institute of Mental Health, and VA HSR&D Research Enhancement Award Program (REAP) PRIME Project (REA 08-266). Emily Wang receives salary support from a career development award from the National Heart Lung Blood Institute (K23 HL103720) and the Yale Clinical Center of Investigation's CTSA Grant (UL1 RR024139). NR 34 TC 2 Z9 2 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD MAR PY 2015 VL 24 IS 2 BP 178 EP 184 DI 10.1111/ajad.12177 PG 7 WC Substance Abuse SC Substance Abuse GA CF8KI UT WOS:000352807600013 PM 25662297 ER PT J AU Walsh, TJ Shores, MM Fox, AE Moore, KP Forsberg, CW Kinsey, CE Heckbert, SR Zeliadt, S Thompson, ML Smith, NL Matsumoto, AM AF Walsh, T. J. Shores, M. M. Fox, A. E. Moore, K. P. Forsberg, C. W. Kinsey, C. E. Heckbert, S. R. Zeliadt, S. Thompson, M. L. Smith, N. L. Matsumoto, A. M. TI Recent trends in testosterone testing, low testosterone levels, and testosterone treatment among Veterans SO Andrology LA English DT Article DE testosterone; trends; Veterans ID LOW SERUM TESTOSTERONE; LATE-ONSET HYPOGONADISM; CARDIOVASCULAR-DISEASE; ANDROGEN DEFICIENCY; INCREASED MORTALITY; OLDER MEN; PREVALENCE AB Low serum testosterone (T) is common and increasingly prevalent with increased age. Recent studies report an epidemic' of T prescribing and concern about unnecessary T treatment. We investigated the number of men tested for T, the prevalence of low serum T levels, and initiation of T treatment among those with low T levels in men treated at Veterans Affairs (VA) facilities in the Northwest US (VISN 20). We identified male Veterans aged 40-89years and examined yearly proportions of men tested for T, found to have low T levels (total T<280ng/dL, free T<34pg/mL, or bioavailable T<84ng/dL), and subsequently treated with T from 2002 to 2011. We excluded men who had T treatment in the year prior and men with diagnoses of prostate or breast cancer. Treatment initiation was defined as the first prescription for T within a year following a low T test. From 2002 to 2011, the yearly population of eligible men in VISN 20 increased from 129247 to 163572. The proportion of men who had serum T tests increased from 3.2% in 2002 to 5.8% in 2011. Among the tested men, the percentage of men with low T levels increased from 35.0 to 47.3%. However, the proportion of men with low T levels who were given T treatment within a year decreased from 31.0 to 28.0%. Despite large increases in T testing, and detection of men with low T levels, there was a slight decrease in the proportion of men with low T levels who were treated with T. The decrease in T treatment during this time period contrasts with other studies and may be related to higher comorbidity in Veterans and/or VA formulary restrictions on the use of transdermal T formulations. C1 [Walsh, T. J.; Heckbert, S. R.] Univ Washington, Seattle, WA 98195 USA. [Shores, M. M.; Fox, A. E.; Moore, K. P.; Forsberg, C. W.; Kinsey, C. E.; Zeliadt, S.; Thompson, M. L.; Smith, N. L.; Matsumoto, A. M.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Thompson, M. L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Matsumoto, A. M.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Matsumoto, A. M.] Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. RP Walsh, TJ (reprint author), Univ Washington, Dept Urol, 1959 NE Pacific St, Seattle, WA 98195 USA. EM walsht@uw.edu FU National Institutes of Health-National Institute on Aging FX This study was supported by an R01 Grant, National Institutes of Health-National Institute on Aging. NR 26 TC 6 Z9 6 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-2919 EI 2047-2927 J9 ANDROLOGY-US JI Andrology PD MAR PY 2015 VL 3 IS 2 BP 287 EP 292 DI 10.1111/andr.12014 PG 6 WC Andrology SC Endocrinology & Metabolism GA CG6HF UT WOS:000353398800019 PM 25684636 ER PT J AU McCully, KS AF McCully, Kilmer S. TI The Active Site of Oxidative Phosphorylation and the Origin of Hyperhomocysteinemia in Aging and Dementia SO ANNALS OF CLINICAL AND LABORATORY SCIENCE LA English DT Article DE homocysteine; cobalamin; thioretinamide; thioretinaco ozonide; nicotinamide adenine dinucleotide; nicotinamide riboside; oxidative phosphorylation; sirtuins; aging; dementia ID NICOTINAMIDE-ADENINE-DINUCLEOTIDE; CHEMICAL PATHOLOGY; RIBOSIDE; ADENOSYLMETHIONINE; HOMOCYSTEINE; METABOLISM; NUTRIENT; DISEASE; NAD(+) AB The active site of oxidative phosphorylation and adenosine triphosphate (ATP) synthesis in mitochondria is proposed to consist of two molecules of thioretinamide bound to cobalamin, forming thioretinaco, complexed with ozone, oxygen, nicotinamide adenine dinucleotide. and inorganic phosphate, TR(2)CoO(3)O(2)NAD+H2PO4-. Reduction of the pyridinium nitrogen of the nicotinamide group by an electron from electron transport complexes initiates polymerization of phosphate with adenosine diphosphate, yielding nicotinamide riboside and ATP bound to thioretinaco ozonide oxygen. A second electron reduces oxygen to hydroperoxyl radical, releasing ATP from the active site. A proton gradient is created within F1F0 ATPase complexes of mitochondria by reaction of protons with reduced nicotinamide riboside and with hydroperoxyl radical, yielding reduced nicotinamide riboside and hydroperoxide. The hyperhomocysteinemia of aging and dementia is attributed to decreased synthesis of adenosyl methionine by thioretinaco ozonide and ATP, causing decreased allosteric activation of cystathionine synthase and decreased allosteric inhibition of methylenetetrahydrofolate reductase and resulting in dysregulation of methionine metabolism. C1 [McCully, Kilmer S.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Pathol & Lab Med Serv, Boston, MA USA. RP McCully, KS (reprint author), Pathol & Lab Med Serv, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM kilmer.mccully@va.gov RI McCully, Kevin/P-5141-2015 OI McCully, Kevin/0000-0001-9850-487X NR 19 TC 5 Z9 5 U1 0 U2 2 PU ASSOC CLINICAL SCIENTISTS PI MIDDLEBURY PA PO BOX 1287, MIDDLEBURY, VT 05753 USA SN 0091-7370 EI 1550-8080 J9 ANN CLIN LAB SCI JI Ann. Clin. Lab. Sci. PD SPR PY 2015 VL 45 IS 2 BP 222 EP 225 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA CG1WH UT WOS:000353065600019 PM 25887881 ER PT J AU Chan, SJ Chai, C Lim, TW Yamamoto, M Lo, EH Lai, MKP Wong, PTH AF Chan, Su Jing Chai, Chou Lim, Tze Wei Yamamoto, Mie Lo, Eng H. Lai, Mitchell Kim Peng Wong, Peter Tsun Hon TI Cystathionine beta-Synthase Inhibition Is a Potential Therapeutic Approach to Treatment of Ischemic Injury SO ASN NEURO LA English DT Article DE cystathioine beta-synthase; hydrogen sulfide; homocysteine; cysteine; oxygen glucose deprivation; stroke ID HYDROGEN-SULFIDE; CELL-DEATH; TOTAL HOMOCYSTEINE; CEREBRAL-ISCHEMIA; OXIDATIVE STRESS; SH-SY5Y CELLS; PC12 CELLS; RAT-BRAIN; CYSTEINE; STROKE AB Hydrogen sulfide (H2S) has been reported to exacerbate stroke outcome in experimental models. Cystathionine beta-synthase (CBS) has been implicated as the predominant H2S-producing enzyme in central nervous system. When SH-SY5Y cells were transfected to overexpress CBS, these cells were able to synthesize H2S when exposed to high levels of enzyme substrates but not substrate concentrations that may reflect normal physiological conditions. At the same time, these cells demonstrated exacerbated cell death when subjected to oxygen and glucose deprivation (OGD) together with high substrate concentrations, indicating that H2S production has a detrimental effect on cell survival. This effect could be abolished by CBS inhibition. The same effect was observed with primary astrocytes exposed to OGD and high substrates or sodium hydrosulfide. In addition, CBS was upregulated and activated by truncation in primary astrocytes subjected to OGD. When rats were subjected to permanent middle cerebral artery occlusion, CBS activation was also observed. These results imply that in acute ischemic conditions, CBS is upregulated and activated by truncation causing an increased production of H2S, which exacerbate the ischemic injuries. Therefore, CBS inhibition may be a viable approach to stroke treatment. C1 [Chan, Su Jing; Lim, Tze Wei; Yamamoto, Mie; Lai, Mitchell Kim Peng; Wong, Peter Tsun Hon] Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore 117548, Singapore. [Chai, Chou] Duke NUS Grad Med Sch, Singapore, Singapore. [Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. RP Wong, PTH (reprint author), Natl Univ Singapore, Clin Res Ctr, Bldg MD11,05-09,10 Med Dr, Singapore 117597, Singapore. EM peter_wong@nuhs.edu.sg FU Biomedical Research Council [BMRC 01/1/21/19/169] FX This work was funded by a grant from the Biomedical Research Council (BMRC 01/1/21/19/169) awarded to PTHW. NR 61 TC 4 Z9 4 U1 0 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1759-0914 J9 ASN NEURO JI ASN Neuro PD MAR-APR PY 2015 VL 7 IS 2 DI 10.1177/1759091415578711 PG 14 WC Neurosciences SC Neurosciences & Neurology GA CG4AU UT WOS:000353223200001 ER PT J AU Whirledge, SD Garcia, JM Smith, RG Lamb, DJ AF Whirledge, Shannon D. Garcia, Jose M. Smith, Roy G. Lamb, Dolores J. TI Ghrelin Partially Protects Against Cisplatin-Induced Male Murine Gonadal Toxicity in a GHSR-1a-Dependent Manner SO BIOLOGY OF REPRODUCTION LA English DT Article DE cell death; cisplatin; fertility; ghrelin; spermatogenesis ID HORMONE SECRETAGOGUE RECEPTOR; HUMAN ENDOTHELIAL-CELLS; LONG-TERM TOXICITY; TESTICULAR CANCER; RAT TESTIS; PROSTATE-CANCER; MOUSE TESTIS; DOUBLE-BLIND; LUNG-CANCER; CHEMOTHERAPY AB The chemotherapeutic drug cisplatin causes a number of dose-dependent side effects, including cachexia and testicular damage. Patients receiving a high cumulative dose of cisplatin may develop permanent azoospermia and subsequent infertility. Thus, the development of chemotherapeutic regimens with the optimal postsurvival quality of life (fertility) is of high importance. This study tested the hypothesis that ghrelin administration can prevent or minimize cisplatin-induced testicular damage and cachexia. Ghrelin and its receptor, the growth hormone secretagogue receptor (GHSR-1a), are expressed and function in the testis. Targeted deletion of ghrelin, or its receptor, significantly increases the rate of cell death in the testis, suggesting a protective role. Intraperitoneal administration of vehicle, ghrelin, or cisplatin alone or in combination with ghrelin, in cycles of 9 or 18 days, to adult male C57Bl/6 mice was performed. Body weight was measured daily and testicular and epididymal weight, sperm density and motility, testicular histology, and testicular cell death were analyzed at the time of euthanization. Ghrelin coadministration decreased the severity of cisplatin-induced cachexia and gonadal toxicity. Body, testicular, and epididymal weights significantly increased as testicular cell death decreased with ghrelin coadministration. The widespread damage to the seminiferous epithelium induced by cisplatin administration was less severe in mice simultaneously treated with ghrelin. Furthermore, ghrelin diminished the deleterious effects of cisplatin on testis and body weight homeostasis in wild-type but not Ghsr(-/-) mice, showing that ghrelin's actions are mediated via GHSR. Ghrelin or more stable GHSR agonists potentially offer a novel therapeutic approach to minimize the testicular damage that occurs after gonadotoxin exposure. C1 [Whirledge, Shannon D.; Lamb, Dolores J.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Lamb, Dolores J.] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. [Lamb, Dolores J.] Baylor Coll Med, Ctr Reprod Med, Houston, TX 77030 USA. [Garcia, Jose M.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Div Endocrinol Diabet & Metab, Houston, TX 77030 USA. [Smith, Roy G.] Scripps Res Inst, Dept Metab & Aging, Jupiter, FL USA. RP Lamb, DJ (reprint author), Baylor Coll Med, Dept Urol, One Baylor Plaza Rm N730, Houston, TX 77030 USA. EM dlamb@bcm.tmc.edu FU National Institute of Kidney and Digestive Disease, National Institutes of Health (NIH) [T32 DK007763-06]; Department of Veterans Affairs (MREP); NIH [AG019230, HD060870, AG040583]; Department of Veterans Affairs (SCNCDA); Department of Veterans Affairs [MERIT BX000507] FX Supported in part by a grant from the National Institute of Kidney and Digestive Disease, National Institutes of Health (NIH), T32 DK007763-06 to D.J.L. (trainee: S.D.W.), the Department of Veterans Affairs (MREP, SCNCDA, and MERIT BX000507 to J.M.G.), NIH AG019230 (R.G.S.), and NIH HD060870 and AG040583 (J.M.G.). Presented in part at the Endocrine Society's 90th Annual Meeting, June 15-18, 2008, San Francisco, California. NR 69 TC 4 Z9 5 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 EI 1529-7268 J9 BIOL REPROD JI Biol. Reprod. PD MAR 1 PY 2015 VL 92 IS 3 AR 76 DI 10.1095/biolreprod.114.123570 PG 11 WC Reproductive Biology SC Reproductive Biology GA CG3XS UT WOS:000353213500006 PM 25631345 ER PT J AU Pursnani, A Chou, ET Zakroysky, P Deano, RC Mamuya, WS Woodard, PK Nagurney, JT Fleg, JL Lee, H Schoenfeld, D Udelson, JE Hoffmann, U Truong, QA AF Pursnani, Amit Chou, Eric T. Zakroysky, Pearl Deano, Roderick C. Mamuya, Wilfred S. Woodard, Pamela K. Nagurney, John T. Fleg, Jerome L. Lee, Hang Schoenfeld, David Udelson, James E. Hoffmann, Udo Truong, Quynh A. TI Use of Coronary Artery Calcium Scanning Beyond Coronary Computed Tomographic Angiography in the Emergency Department Evaluation for Acute Chest Pain The ROMICAT II Trial SO Circulation-Cardiovascular Imaging LA English DT Article DE acute coronary syndrome; hospital emergency service; multidetector-row computed tomography ID AMERICAN-HEART-ASSOCIATION; ELECTRON-BEAM TOMOGRAPHY; CT ANGIOGRAPHY; TUBE-VOLTAGE; ASSISTED TOMOGRAPHY; RADIATION-EXPOSURE; IMAGE QUALITY; FOLLOW-UP; CALCIFICATION; RISK AB Background-Whether a coronary artery calcium (CAC) scan provides added value to coronary computed tomographic angiography (CCTA) in emergency department patients with acute chest pain remains unsettled. We sought to determine the value of CAC scan in patients with acute chest pain undergoing CCTA. Methods and Results-In the multicenter Rule Out Myocardial Infarction using Computer-Assisted Tomography (ROMICAT) II trial, we enrolled low-intermediate risk emergency department patients with symptoms suggesting acute coronary syndrome (ACS). In this prespecified subanalysis of 473 patients (54 +/- 8 years, 53% men) who underwent both CAC scanning and CCTA, the ACS rate was 8%. Overall, 53% of patients had CAC=0 of whom 2 (0.8%) developed ACS, whereas 7% had CAC>400 with 49% whom developed ACS. C-statistic of CAC>0 was 0.76, whereas that using the optimal cut point of CAC >= 22 was 0.81. Continuous CAC score had lower discriminatory capacity than CCTA (c-statistic, 0.86 versus 0.92; P=0.03). Compared with CCTA alone, there was no benefit combining CAC score with CCTA (c-statistic, 0.93; P=0.88) or with selective CCTA strategies after initial CAC>0 or optimal cut point CAC >= 22 (P >= 0.09). Mean radiation dose from CAC acquisition was 1.4 +/- 0.7 mSv. Higher CAC scores resulted in more nondiagnostic CCTA studies although the majority remained interpretable. Conclusions-In emergency department patients with acute chest pain, CAC score does not provide incremental value beyond CCTA for ACS diagnosis. CAC=0 does not exclude ACS, nor a high CAC score preclude interpretation of CCTA in most patients. Thus, CAC results should not influence the decision to proceed with CCTA, and the decision to perform a CAC scan should be balanced with the additional radiation exposure required. C1 [Pursnani, Amit; Mamuya, Wilfred S.; Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Cardiol,Cardiac MR PET CT Program, Boston, MA USA. [Nagurney, John T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Emergency Dept, Boston, MA USA. [Zakroysky, Pearl; Lee, Hang; Schoenfeld, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biostat Ctr, Boston, MA USA. [Chou, Eric T.] Kaiser Permanente Fontana Med Ctr, Div Cardiol, Fontana, CA USA. [Deano, Roderick C.; Truong, Quynh A.] New York Presbyterian Hosp, Weill Cornell Med Coll, Dalio Inst Cardiovasc Imaging, New York, NY 10021 USA. [Woodard, Pamela K.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. [Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Udelson, James E.] Tufts Med Ctr, Div Cardiol, Boston, MA USA. [Udelson, James E.] Tufts Med Ctr, Ctr Cardiovasc, Boston, MA USA. RP Truong, QA (reprint author), New York Presbyterian Hosp, Weill Cornell Med Coll, Dalio Inst Cardiovasc Imaging, 413 E 69th St,Suite 108, New York, NY 10021 USA. EM qat9001@med.cornell.edu FU National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute [U01HL092040, U01HL092022]; NIH [K23HL098370, L30HL093896]; [NIHT32 HL076136] FX The study was supported by the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (U01HL092040 and U01HL092022). Dr Truong was supported by the NIH (K23HL098370 and L30HL093896). Dr Pursnani was supported by NIHT32 HL076136. NR 35 TC 5 Z9 5 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD MAR PY 2015 VL 8 IS 3 AR e002225 DI 10.1161/CIRCIMAGING.114.002225 PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CG5CW UT WOS:000353309700003 ER PT J AU Pursnani, A Lee, AM Mayrhofer, T Ahmed, W Uthamalingam, S Ferencik, M Puchner, SB Bamberg, F Schlett, CL Udelson, J Hoffmann, U Ghoshhajra, BB AF Pursnani, Amit Lee, Ashley M. Mayrhofer, Thomas Ahmed, Waleed Uthamalingam, Shanmugam Ferencik, Maros Puchner, Stefan B. Bamberg, Fabian Schlett, Christopher L. Udelson, James Hoffmann, Udo Ghoshhajra, Brian B. TI Early Resting Myocardial Computed Tomography Perfusion for the Detection of Acute Coronary Syndrome in Patients With Coronary Artery Disease SO Circulation-Cardiovascular Imaging LA English DT Article DE perfusion; emergency service, hospital; tomography, computed; scanners ID ACUTE CHEST-PAIN; FRACTIONAL FLOW RESERVE; AMERICAN-HEART-ASSOCIATION; CARDIOVASCULAR MAGNETIC-RESONANCE; RANDOMIZED CONTROLLED-TRIAL; LEFT-VENTRICULAR FUNCTION; APPROPRIATE USE CRITERIA; EMERGENCY-DEPARTMENT; CT ANGIOGRAPHY; CARDIAC CT AB Background-Acute rest single-photon emission computed tomography-myocardial perfusion imaging (SPECT-MPI) has high predictive value for acute coronary syndrome (ACS) in emergency department patients. Prior studies have shown excellent agreement between rest/stress computed tomography perfusion (CTP) and SPECT-MPI, but the value of resting CTP (rCTP) in acute chest pain triage remains unclear. We sought to determine the diagnostic accuracy of early rCTP, incremental value beyond obstructive coronary artery disease (CAD; >= 50% stenosis), and compared early rCTP to late stress SPECT-MPI in patients with CAD presenting with suspicion of ACS to the emergency department. Methods and Results-In this prespecified subanalysis of 183 patients (58.1 +/- 10.2 years; 33% women), we included patients with any CAD by coronary computed tomography angiography (CCTA) from Rule Out Myocardial Infarction Using Computer-Assisted Tomography I. rCTP was assessed semiquantitatively, blinded to CAD interpretation. Overall, 31 had ACS and 48 had abnormal rCTP. Sensitivity and specificity of rCTP for ACS were 48% (95% confidence interval [CI], 30%-67%) and 78% (95% CI, 71%-85%), respectively. rCTP predicted ACS (adjusted odds ratio, 3.40 [95% CI, 1.37-8.42]; P=0.008) independently of obstructive CAD, and sensitivity for ACS increased from 77% (95% CI, 59%-90%) for obstructive CAD to 90% (95% CI, 74%-98%) with addition of rCTP (P=0.05). In a subgroup undergoing late rest/stress SPECT-MPI (n=81), CCTA/rCTP had noninferior discriminatory value to CCTA/SPECT-MPI (area under the curve, 0.88 versus 0.90; P=0.64) using a noninferiority margin of 10%. Conclusions-Early rCTP provides incremental value beyond obstructive CAD to detect ACS. CCTA/rCTP is noninferior to CCTA/SPECT-MPI to discriminate ACS and presents an attractive alternative to triage patients presenting with acute chest pain. C1 [Pursnani, Amit] NorthShore Univ Hlth Syst, Div Cardiovasc, Evanston, IL USA. [Pursnani, Amit; Lee, Ashley M.; Mayrhofer, Thomas; Ahmed, Waleed; Uthamalingam, Shanmugam; Ferencik, Maros; Puchner, Stefan B.; Hoffmann, Udo; Ghoshhajra, Brian B.] Massachusetts Gen Hosp, Dept Radiol, Div Cardiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Pursnani, Amit; Lee, Ashley M.; Mayrhofer, Thomas; Ahmed, Waleed; Uthamalingam, Shanmugam; Ferencik, Maros; Puchner, Stefan B.; Hoffmann, Udo; Ghoshhajra, Brian B.] Harvard Univ, Sch Med, Boston, MA USA. [Bamberg, Fabian] Univ Munich, Klinikum Grosshadern, Dept Clin Radiol, D-80539 Munich, Germany. [Schlett, Christopher L.] Univ Heidelberg Hosp, Dept Diagnost & Intervent Radiol, Heidelberg, Germany. [Udelson, James] Tufts Med Ctr, Div Cardiol & Cardiovasc Ctr, Boston, MA USA. RP Pursnani, A (reprint author), Northwestern Univ, Evanston Hosp, Div Cardiol, Walgreen Bldg 3rd Floor,2650 Ridge Ave, Evanston, IL 60201 USA. EM apursnani@northshore.org FU National Heart, Lung, and Blood Institute [R01 HL080053, 5K24HL113128]; National Institutes of Health [T32 HL076136]; American Heart Association [13FTF1645000] FX This work was supported by grants from the National Heart, Lung, and Blood Institute (R01 HL080053 and 5K24HL113128). Drs Pursnani, Ahmed, and Dr Uthamalingam received funding from the National Institutes of Health T32 HL076136. Dr Ferencik was supported by a grant from the American Heart Association 13FTF1645000 NR 39 TC 4 Z9 4 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD MAR PY 2015 VL 8 IS 3 AR e002404 DI 10.1161/CIRCIMAGING.114.002404 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CG5CW UT WOS:000353309700004 PM 25752898 ER PT J AU Brennan, JM Al-Hejily, W Dai, D Shaw, RE Trilesskaya, M Rao, SV Brilakis, ES Anstrom, KJ Messenger, JC Peterson, ED Douglas, PS Sketch, MH AF Brennan, J. Matthew Al-Hejily, Wesam Dai, David Shaw, Richard E. Trilesskaya, Marina Rao, Sunil V. Brilakis, Emmanouil S. Anstrom, Kevin J. Messenger, John C. Peterson, Eric D. Douglas, Pamela S. Sketch, Michael H., Jr. TI Three-Year Outcomes Associated With Embolic Protection in Saphenous Vein Graft Intervention Results in 49 325 Senior Patients in the Medicare-Linked National Cardiovascular Data Registry CathPCI Registry SO Circulation-Cardiovascular Interventions LA English DT Article DE embolic protection devices ID AORTOCORONARY BYPASS GRAFTS; BARE-METAL STENTS; DISTAL PROTECTION; PERCUTANEOUS INTERVENTION; TRIAL; LESIONS; LINKING; DEVICES; EVENTS; STILL AB Background-Information is limited on contemporary use and outcomes of embolic protection devices (EPDs) in saphenous vein graft interventions. Methods and Results-We formed a longitudinal cohort (2005-2009; n=49 325) by linking National Cardiovascular Data Registry CathPCI Registry to Medicare claims to examine the association between EPD use and both procedural and long-term outcomes among seniors (65+ years), adjusting for clinical factors using propensity and instrumental variable methodologies. Prespecified high-risk subgroups included acute coronary syndrome and de novo or graft body lesions. EPDs were used in 21.2% of saphenous vein grafts (median age, 75; 23% women) and were more common in acute coronary syndrome (versus non-acute coronary syndrome; 22% versus 19%), de novo (versus restenotic; 22% versus 14%), and graft body lesions (versus aortic and distal anastomosis; 24% versus 20% versus 8%, respectively). EPDs were associated with a slightly higher incidence of procedural complications, including no reflow (3.9% versus 2.8%; P<0.001), vessel dissection (1.3% versus 1.1%; P=0.05), perforation (0.7% versus 0.4%; P=0.001), and periprocedural myocardial infarction (2.8% versus 1.8%; P<0.001). By 3 years, death, myocardial infarction, and repeat revascularization occurred in 25%, 15%, and 30% of cases, respectively. EPD use was associated with a similar adjusted risk of death (propensity score-matched hazard ratio, 0.96; 95% confidence interval, 0.91-1.02), myocardial infarction (propensity score-matched hazard ratio, 1.00; 95% confidence interval, 0.93-1.09), and repeat revascularization (propensity score-matched hazard ratio, 1.02; 95% confidence interval, 0.96-1.08) in the overall cohort and high-risk subgroups. Conclusions-In this contemporary cohort, EPDs were used more commonly among patients with high-risk clinical indications, yet there was no evidence of improved acute-or long-term outcomes. Further prospective studies are needed to support routine EPD use. C1 [Brennan, J. Matthew; Al-Hejily, Wesam; Dai, David; Rao, Sunil V.; Anstrom, Kevin J.; Peterson, Eric D.; Douglas, Pamela S.; Sketch, Michael H., Jr.] Duke Clin Res Inst, Durham, NC USA. [Shaw, Richard E.] Sutter Pacific Heart Ctr, San Francisco, CA USA. [Trilesskaya, Marina] Carolina Pacific Med Ctr, San Francisco, CA USA. [Brilakis, Emmanouil S.] Vet Affairs North Texas Healthcare Syst, Dallas, TX USA. [Brilakis, Emmanouil S.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Messenger, John C.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Brennan, JM (reprint author), Duke Univ, Med Ctr, Div Cardiovasc Med, 2400 Pratt St, Durham, NC 27705 USA. EM j.matthew.brennan@dm.duke.edu OI Brilakis, Emmanouil/0000-0001-9416-9701 FU Duke Clinical Research Institute, Durham, NC FX This work was supported internally by the Duke Clinical Research Institute, Durham, NC. NR 28 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7640 EI 1941-7632 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD MAR PY 2015 VL 8 IS 3 AR e001403 DI 10.1161/CIRCINTERVENTIONS.114.001403 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CG5CY UT WOS:000353309900001 PM 25714391 ER PT J AU Schnurr, PP Chard, KM Ruzek, J Chow, BK Shih, MC Resick, PA Foa, EB Marx, BP Huang, GD Lu, Y AF Schnurr, Paula P. Chard, Kathleen M. Ruzek, Josef. Chow, Bruce K. Shih, Mei-Chiung Resick, Patricia A. Foa, Edna B. Marx, Brian P. Huang, Grant D. Lu, Ying TI Design of VA Cooperative Study #591: CERV-PTSD, Comparative Effectiveness Research in Veterans with PTSD SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Comparative effectiveness; Posttraumatic stress disorder; Veterans; Cognitive-behavioral therapy; Randomized clinical trial ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-PROCESSING THERAPY; NATIONAL COMORBIDITY SURVEY; PROLONGED EXPOSURE; SURVEY REPLICATION; RANDOMIZED-TRIAL; AFFAIRS; PSYCHOTHERAPY; PREVALENCE; DEPRESSION AB CERV-PTSD is a randomized controlled trial of two of the most effective treatments for PTSD, Prolonged Exposure (PE) and Cognitive Processing Therapy (CPT). Despite solid evidence that both treatments are effective, there is limited evidence about their effectiveness relative to one another. The primary objective is to compare the effectiveness of PE and CPT for reducing PTSD symptom severity in a healthcare system that offers both treatments.The secondary objective is to compare the effectiveness of PE and CPT for reducing the severity of comorbid mental health problems and service utilization as well as improving functioning and quality of life. The tertiary objective is to examine whether discrepancy between patient preferences and treatment assignment reduces the effectiveness of each treatment. Exploratory analyses will examine whether demographic and clinical characteristics predict differential response to PE and CPT. The study is designed to randomize 900 male and female veterans with PTSD due to any traumatic military event to receive PE or CPT. The standard dose of treatment is 12 weekly sessions but veterans who improve more rapidly may finish in fewer sessions and veterans who improve more slowly may have additional sessions. The primary outcome is improvement in PTSD symptoms, measured during and after treatment and then 3 and 6 months later. As a large multi-site trial with men and women, CERV-PTSD is designed to advance the delivery of care for PTSD by providing conclusive information about whether one treatment is better than the other,, overall, and for different types of patients. Published by Elsevier Inc. C1 [Schnurr, Paula P.] Natl Ctr PTSD, Execut Div, White River Jct, VT 05009 USA. [Schnurr, Paula P.] Geisel Sch Med Dartmouth, Hanover, NH USA. [Chard, Kathleen M.] Cincinnati VA Med Ctr, Cincinnati, OH USA. [Chard, Kathleen M.] Univ Cincinnati, Cincinnati, OH USA. [Ruzek, Josef.] Natl Ctr PTSD, Disseminat & Training Div, Palo Alto, CA USA. [Ruzek, Josef.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Chow, Bruce K.; Shih, Mei-Chiung; Lu, Ying] VA Cooperat Studies Program Coordinating Ctr, Palo Alto, CA USA. [Shih, Mei-Chiung; Lu, Ying] Stanford Univ, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA. [Resick, Patricia A.] Duke Univ, Sch Med, Durham, NC USA. [Foa, Edna B.] Univ Penn, Philadelphia, PA 19104 USA. [Marx, Brian P.] Boston Univ, Sch Med, Natl Ctr PTSD, Behav Sci Div, Boston, MA 02118 USA. [Marx, Brian P.] VA Boston Healthcare Syst, Boston, MA USA. [Huang, Grant D.] Dept Vet Affairs Off Res & Dev, Cooperat Studies Program Cent Off, Washington, DC USA. RP Schnurr, PP (reprint author), VA Med Ctr, Natl Ctr PTSD 116D, White River Jct, VT 05009 USA. EM paula.schnurr@dartmouth.edu FU VA Cooperative Studies Program FX This study is being conducted with funding from the VA Cooperative Studies Program. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs or any US government agency. Trial registration information for CSP #591: clinicaltrials.gov Identifier NCT01928732. NR 61 TC 8 Z9 8 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD MAR PY 2015 VL 41 BP 75 EP 84 DI 10.1016/j.cct.2014.11.017 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA CG0YQ UT WOS:000353000500010 PM 25457792 ER PT J AU Zimmerman, RF Belanger, ES Pfeiffer, CD AF Zimmerman, Robert F. Belanger, Elizabeth S. Pfeiffer, Christopher D. TI Skin Infections in Returned Travelers: an Update SO CURRENT INFECTIOUS DISEASE REPORTS LA English DT Article DE Skin infection; Travel medicine; Cutaneous larva migrans; Cutaneous leishmaniasis; Tungiasis; Myiasis; Antibiotic resistance; Skin and soft tissue infection; Measles; Chikungunya ID CUTANEOUS LARVA MIGRANS; GEOSENTINEL SURVEILLANCE; LEISHMANIASIS; OUTBREAK; COMMUNITY; DIAGNOSIS; MEASLES; MILTEFOSINE; ELIMINATION; TUNGIASIS AB Dermatologic manifestations of travel-related illness are particularly vexing due to the broad differential diagnosis and clinicians' unfamiliarity with uncommonly seen diseases. This paper aims to educate and update the reader on selected infectious diseases in the returned traveler whose disease manifestations are primarily dermatologic. First, the evolving epidemiology of these infections is examined; understanding the geographic distribution of infectious etiologies helps refine and narrow the differential diagnosis. This is followed by a discussion of six important clinical syndromes including cutaneous larva migrans (CLM), cutaneous leishmaniasis, tungiasis, myiasis, antibiotic-resistant skin and soft tissue infection, and selected infections associated with fever and rash (e.g., measles, chikungunya virus infection, dengue fever, rickettsial spotted fevers). Familiarity with these syndromes and a situational awareness of their epidemiology will facilitate a prompt, accurate diagnosis and lead to appropriate treatment and prevention of further disease spread. C1 [Zimmerman, Robert F.; Belanger, Elizabeth S.; Pfeiffer, Christopher D.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Pfeiffer, Christopher D.] Portland VA Med Ctr, Dept Hosp & Specialty Med, Portland, OR 97239 USA. RP Pfeiffer, CD (reprint author), Portland VA Med Ctr, Dept Hosp & Specialty Med, POB 1034 P3-ID, Portland, OR 97239 USA. EM pfeiffec@ohsu.edu FU Oregon Health Authority FX Elizabeth Belanger has no conflicts of interest. Christopher Pfeiffer received funding for other work from Oregon Health Authority. NR 47 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3847 EI 1534-3146 J9 CURR INFECT DIS REP JI Curr. Infect. Dis. Rep. PD MAR PY 2015 VL 17 IS 3 AR 10 DI 10.1007/s11908-015-0467-8 PG 6 WC Infectious Diseases SC Infectious Diseases GA CG7VY UT WOS:000353515300003 ER PT J AU Moura, LMVR Mendez, DY De Jesus, J Andrade, RA Hoch, DB AF Moura, Lidia M. V. R. Mendez, Diego Yacaman De Jesus, Jonathan Andrade, Rogger A. Hoch, Daniel B. TI Quality care in epilepsy: Women's counseling and its association with folic acid prescription or recommendation SO EPILEPSY & BEHAVIOR LA English DT Article DE Epilepsy Quality Measures; Epilepsy outcomes; Safety counseling; Women's counseling; Health-care reform; Pay for performance ID PATIENT; MANAGEMENT; PREGNANCY; SPECIALTY; KNOWLEDGE; PEOPLE AB Objective: This study aimed to determine if annual counseling about contraception and pregnancy in the setting of treatment for epilepsy is associated with increased recommending or prescribing of folate. Methods: This is a retrospective cohort study with medical record abstraction. We selected records from 77 women of childbearing age who had two or more visits for epilepsy at a neurology clinic. The assessment included a review of documentation from the first three visits for epilepsy within a 24-month follow-up window. We defined perfect adherence to annual counseling about the impact of epilepsy treatment on contraception or pregnancy as defect-free care for women (DFCW). A recommendation that the patient take over-the-counter folate or a prescription for folate was independently abstracted from the chart at each visit. Results: The group of patients who received DFCW (N = 28, 36.36%) and the group who did not receive DFCW (N = 49, 63.63%) were comparable with respect to age, disease duration, baseline history of drug-resistant epilepsy (DRE), presence of concurrent psychiatric disease, epileptologist involvement, number of antiepileptic drugs (AEDs) prescribed, seizure type, and etiology. Twenty (71.4%) patients in the DFCW group and 42 (85.7%) in the non-DFCW group were not recommended or prescribed folic acid (p = 0.12). Conclusions: Even with annual documentation of counseling about howepilepsy treatment may affect contraception and pregnancy, the "action" of prescribing or recommending folic acid during the ensuing 24 months is frequently omitted. (C) 2015 Elsevier Inc. All rights reserved. C1 [Moura, Lidia M. V. R.; Mendez, Diego Yacaman; De Jesus, Jonathan; Andrade, Rogger A.; Hoch, Daniel B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Moura, LMVR (reprint author), Massachusetts Gen Hosp, Wang 720 Neurol,55 Fruit St, Boston, MA 02114 USA. EM lidia.moura@mgh.harvard.edu; dymendez@partners.org; jdejesus5@partners.org; raandrade@partners.org; dhoch@partners.org FU Massachusetts General Hospital Center of Expertise in Quality and Safety [223639]; Eisai, inc [2013D004806] FX This study was supported by the Massachusetts General Hospital Center of Expertise in Quality and Safety (Grant number: 223639) and the Eisai, inc (Grant number: 2013D004806). NR 21 TC 5 Z9 5 U1 2 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD MAR PY 2015 VL 44 BP 151 EP 154 DI 10.1016/j.yebeh.2014.12.039 PG 4 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA CG4AI UT WOS:000353221600027 PM 25705826 ER PT J AU Hall, RK Landerman, LR O'Hare, AM Anderson, RA Colon-Emeric, CS AF Hall, Rasheeda K. Landerman, Lawrence R. O'Hare, Ann M. Anderson, Ruth A. Colon-Emeric, Cathleen S. TI Chronic kidney disease and recurrent falls in nursing home residents: A retrospective cohort study SO GERIATRIC NURSING LA English DT Article DE Skilled nursing facility; Renal insufficiency; Frail elderly ID GLOMERULAR-FILTRATION-RATE; RISK-FACTORS; RENAL-INSUFFICIENCY; SERUM CREATININE; COCKCROFT-GAULT; PREVALENCE; PREVENTION; ANEMIA; COMPLICATIONS; EPIDEMIOLOGY AB This study examined whether chronic kidney disease (CKD) is associated with recurrent falls in older adults in nursing homes (NHs). We used data abstracted over a six month period from 510 NH residents with a history of falls. Thirty-five percent of the NH residents had CKD. In adjusted analyses, the incidence of recurrent falls was similar in those with and without CKD [fall rate ratio (FRR) 1.00, 95% confidence interval (Cl) 0.97-1.02]. Orthostatic hypotension (FRR 1.52, 95% Cl 1.12-2.05), history of falls during the prior six month period (FRR 1.25, 95% CI 1.05-1.49), cane or walker use (FRR 1.64, 95% Cl 1.16-2.33), and ambulatory dysfunction (FRR 1.47, 95% Cl 1.23-1.75) were independently associated with increased fall rate. CKD was not an important predictor of falls in this cohort of nursing home residents with prior falls. Instead, traditional fall risk factors were much more strongly associated with recurrent falls. Published by Elsevier Inc. C1 [Hall, Rasheeda K.] Duke Univ, Med Ctr, Div Nephrol, Dept Med, Durham, NC 27710 USA. [Hall, Rasheeda K.; Colon-Emeric, Cathleen S.] Durham VA Geriatr Res Educ & Clin Ctr, Durham, NC 27705 USA. [Landerman, Lawrence R.; Colon-Emeric, Cathleen S.] Duke Univ, Med Ctr, Div Geriatr, Dept Med, Durham, NC 27710 USA. [Landerman, Lawrence R.; Anderson, Ruth A.] Duke Univ, Sch Nursing, Durham, NC 27710 USA. [O'Hare, Ann M.] VA Puget Sound Healthcare Syst, Dept Med, Seattle, WA 98108 USA. [O'Hare, Ann M.] HSR&D Ctr Excellence, Seattle, WA 98108 USA. [O'Hare, Ann M.] Univ Washington, Div Nephrol, Dept Med, Seattle, WA 98195 USA. RP Hall, RK (reprint author), Box DUMC 2747,2424 Erwin Rd Suite 605, Durham, NC 27710 USA. EM rasheeda.stephens@dm.duke.edu OI Hall, Rasheeda/0000-0002-3057-4828 FU National Institute on Aging of the National Institutes of Health [P30AG028716]; National Institute of Nursing Research [R01NR003178]; Office of Academic Affiliations, US Department of Veterans Affairs FX Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under Award Number P30AG028716. It was also supported by the National Institute of Nursing Research (R01NR003178). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.; Dr. Hall was supported in part by a fellowship award from the Office of Academic Affiliations, US Department of Veterans Affairs. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs or the United States government. NR 29 TC 1 Z9 1 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4572 EI 1528-3984 J9 GERIATR NURS JI Geriatr. Nurs. PD MAR-APR PY 2015 VL 36 IS 2 BP 136 EP 141 DI 10.1016/j.gerinurse.2014.12.012 PG 6 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA CG3LU UT WOS:000353182500008 PM 25616732 ER PT J AU Gilmore-Bykovskyi, AL AF Gilmore-Bykovskyi, Andrea L. TI Caregiver person-centeredness and behavioral symptoms during mealtime interactions: Development and feasibility of a coding scheme SO GERIATRIC NURSING LA English DT Article DE Dementia; Behavioral Symptoms; Person-Centered Caregiving; Video-observation ID NURSING-HOME RESIDENTS; CLUSTER-RANDOMIZED-TRIAL; HIGH AGREEMENT; OLDER-ADULTS; DEMENTIA-CARE; LOW KAPPA; INTERVENTIONS; DIFFICULTIES; AGITATION; RELIABILITY AB Mealtime behavioral symptoms are distressing and frequently interrupt eating for the individual experiencing them and others in the environment. A computer-assisted coding scheme was developed to measure caregiver person-centeredness and behavioral symptoms for nursing home residents with dementia during mealtime interactions. The purpose of this pilot study was to determine the feasibility, ease of use, and inter-observer reliability of the coding scheme, and to explore the clinical utility of the coding scheme. Trained observers coded 22 observations. Data collection procedures were acceptable to participants. Overall, the coding scheme proved to be feasible, easy to execute and yielded good to very good inter-observer agreement following observer re-training. The coding scheme captured clinically relevant, modifiable antecedents to mealtime behavioral symptoms, but would be enhanced by the inclusion of measures for resident engagement and consolidation of items for measuring caregiver person-centeredness that co-occurred and were difficult for observers to distinguish. (C) 2015 Elsevier Inc. All rights reserved. C1 [Gilmore-Bykovskyi, Andrea L.] US Dept Vet Affairs, GRECC, William S Middleton Hosp, Madison, WI 53705 USA. [Gilmore-Bykovskyi, Andrea L.] Univ Wisconsin, Sch Nursing, Madison, WI 53705 USA. RP Gilmore-Bykovskyi, AL (reprint author), US Dept Vet Affairs, GRECC, William S Middleton Hosp, Madison, WI 53705 USA. EM algilmore@wisc.edu FU National Hartford Centers of Gerontological Nursing Excellence Patricia G. Archbold Scholar Program; Claire M. Fagin Postdoctoral Fellowship Program; Virginia Stone Research Grant in Clinical Gerontology from the American Nurses Foundation; Nurses Foundation of Wisconsin; University of Wisconsin-Madison School of Nursing Eckburg Research Award; National Center for Research Resources, National Institutes of Health [1UL1RR025011] FX This work was supported by the National Hartford Centers of Gerontological Nursing Excellence Patricia G. Archbold Scholar Program and Claire M. Fagin Postdoctoral Fellowship Program. This research was supported by the Virginia Stone Research Grant in Clinical Gerontology from the American Nurses Foundation, and in part by the Nurses Foundation of Wisconsin and University of Wisconsin-Madison School of Nursing Eckburg Research Award. Dr. Gilmore-Bykovskyi's time during preparation of this manuscript was also supported by the William S. Middleton Veterans Affairs Hospital in Madison, WI. This work is also supported, in part, by the Clinical and Translational Science Award program of the National Center for Research Resources, National Institutes of Health (1UL1RR025011). The content is solely the responsibility of the author and does not necessarily represent the official views of the NIH. The author would like to acknowledge Drs. Louis Medvene and Carissa Coleman for early consultation in planning this research. This work was presented at the Gerontological Society of America's 2014 Annual Scientific Meeting in Washington, D.C. NR 30 TC 0 Z9 0 U1 5 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4572 EI 1528-3984 J9 GERIATR NURS JI Geriatr. Nurs. PD MAR-APR PY 2015 VL 36 IS 2 SU S BP S10 EP S15 DI 10.1016/j.gerinurse.2015.02.018 PG 6 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA CG3LW UT WOS:000353182700003 PM 25784080 ER PT J AU De Santis, ML Myrick, H Lamis, DA Pelic, CP Rhue, C York, J AF De Santis, Mark L. Myrick, Hugh Lamis, Dorian A. Pelic, Christopher P. Rhue, Collete York, Janet TI Suicide-specific Safety in the Inpatient Psychiatric Unit SO Issues in Mental Health Nursing LA English DT Article ID TOWER-OF-BABEL; MENTAL-HEALTH; COLLABORATIVE ASSESSMENT; RISK-ASSESSMENT; EMERGENCY-DEPARTMENT; REVISED NOMENCLATURE; VA PATIENTS; PREVENTION; MANAGEMENT; VETERANS AB In total, 75% of suicides reported to the Joint Commission as sentinel events since 1995, have occurred in psychiatric settings. Ensuring patient safety is one of the primary tasks of inpatient psychiatric units. A review of inpatient suicide-specific safety components, inclusive of incidence and risk; guidelines for evidence-based care; environmental safety; suicide risk assessment; milieu observation and monitoring; psychotherapeutic interventions; and documentation is provided. The Veterans Health Administration (VA) has been recognized as an exemplar system in suicide prevention. A VA inpatient psychiatric unit is used to illustrate the operationalization of a culture of suicide-specific safety. We conclude by describing preliminary unit outcomes and acknowledging limitations of suicide-specific inpatient care and gaps in the current inpatient practices and research on psychotherapeutic interventions, observation, and monitoring. C1 [De Santis, Mark L.; Pelic, Christopher P.; Rhue, Collete; York, Janet] Ralph H Johnson VAMC, Mental Hlth Serv Line, Charleston, SC USA. [Myrick, Hugh] Med Univ S Carolina, Psychiat & Behav Sci, Charleston, SC 29425 USA. [Lamis, Dorian A.] Emory Univ, Sch Med, Atlanta, GA 30303 USA. RP Lamis, DA (reprint author), Emory Univ, Sch Med, 80 Jesse Hill Jr Dr, Atlanta, GA 30303 USA. EM Dalamis@gmail.com OI De Santis, Mark/0000-0002-3611-1779 NR 91 TC 4 Z9 4 U1 6 U2 10 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0161-2840 EI 1096-4673 J9 ISSUES MENT HEALTH N JI Issues Ment. Health Nurs. PD MAR PY 2015 VL 36 IS 3 BP 190 EP 199 DI 10.3109/01612840.2014.961625 PG 10 WC Nursing; Psychiatry SC Nursing; Psychiatry GA CG4ZO UT WOS:000353298300005 PM 25898018 ER PT J AU Fujiwara, K Inoue, T Yorifuji, N Iguchi, M Sakanaka, T Narabayashi, K Kakimoto, K Nouda, S Okada, T Ishida, K Abe, Y Masuda, D Takeuchi, T Fukunishi, S Umegaki, E Akiba, Y Kaunitz, JD Higuchi, K AF Fujiwara, Kaori Inoue, Takuya Yorifuji, Naoki Iguchi, Munetaka Sakanaka, Taisuke Narabayashi, Ken Kakimoto, Kazuki Nouda, Sadaharu Okada, Toshihiko Ishida, Kumi Abe, Yosuke Masuda, Daisuke Takeuchi, Toshihisa Fukunishi, Shinya Umegaki, Eiji Akiba, Yasutada Kaunitz, Jonathan D. Higuchi, Kazuhide TI Combined treatment with dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin and elemental diets reduced indomethacin-induced intestinal injury in rats via the increase of mucosal glucagon-like peptide-2 concentration SO JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION LA English DT Article DE GLP-1; GLP-2; DPP4; DPP8; sitagliptin ID INFLAMMATORY-BOWEL-DISEASE; LOW-DOSE ASPIRIN; CROHNS-DISEASE; BICARBONATE SECRETION; EXPERIMENTAL COLITIS; IV; MICE; TEDUGLUTIDE; EXPRESSION; IMPACT AB The gut incretin glucagon-like peptide-1 (GLP-1) and the intestinotropic hormone GLP-2 are released from enteroendocrine L cells in response to ingested nutrients. Treatment with an exogenous GLP-2 analogue increases intestinal villous mass and prevents intestinal injury. Since GLP-2 is rapidly degraded by dipeptidyl peptidase 4 (DPP4), DPP4 inhibition may be an effective treatment for intestinal ulcers. We measured mRNA expression and DPP enzymatic activity in intestinal segments. Mucosa! DPP activity and GLP concentrations were measured after administration of the DPP4 inhibitor sitagliptin (STG). Small intestinal ulcers were induced by indomethacin (IM) injection. STG was given before IM treatment, or orally administered after IM treatment with or without an elemental diet (ED). DPP4 mRNA expression and enzymatic activity were high in the jejunum and ileum. STG dose-dependently suppressed ileal mucosal enzyme activity. Treatment with STG prior to IM reduced small intestinal ulcer scores. Combined treatment with STG and ED accelerated intestinal ulcer healing, accompanied by increased mucosa! GLP-2 concentrations. The reduction of ulcers by ED and STG was reversed by co-administration of the GLP-2 receptor antagonist. DPP4 inhibition combined with luminal nutrients, which up-regulate mucosal concentrations of GLP-2, may be an effective therapy for the treatment of small intestinal ulcers. C1 [Fujiwara, Kaori; Inoue, Takuya; Yorifuji, Naoki; Iguchi, Munetaka; Sakanaka, Taisuke; Narabayashi, Ken; Kakimoto, Kazuki; Nouda, Sadaharu; Okada, Toshihiko; Ishida, Kumi; Abe, Yosuke; Masuda, Daisuke; Takeuchi, Toshihisa; Fukunishi, Shinya; Umegaki, Eiji; Higuchi, Kazuhide] Osaka Med Coll, Dept Internal Med 2, Takatsuki, Osaka 5698686, Japan. [Akiba, Yasutada; Kaunitz, Jonathan D.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Akiba, Yasutada; Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Dept Surg, Los Angeles, CA 90024 USA. RP Inoue, T (reprint author), Osaka Med Coll, Dept Internal Med 2, 2-7 Daigakumachi, Takatsuki, Osaka 5698686, Japan. EM ureuretakuwan@yahoo.co.jp FU NIDDK NIH HHS [R01 DK054221] NR 34 TC 4 Z9 5 U1 0 U2 3 PU JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION PI KYOTO PA KYOTO PREFECTURAL UNIV MED, GRAD SCH MEDICAL SCIENCE, DEPT MOLECULAR GASTROENTEROLOGY & HEPATOLOGY, KYOTO, 602-8566, JAPAN SN 0912-0009 EI 1880-5086 J9 J CLIN BIOCHEM NUTR JI J. Clin. Biochem. Nutr. PD MAR 1 PY 2015 VL 56 IS 2 BP 155 EP 162 DI 10.3164/jcbn.14-111 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CG6TE UT WOS:000353434500011 PM 25759522 ER PT J AU Klann, JG Mendis, M Phillips, LC Goodson, AP Rocha, BH Goldberg, HS Wattanasin, N Murphy, SN AF Klann, Jeffrey G. Mendis, Michael Phillips, Lori C. Goodson, Alyssa P. Rocha, Beatriz H. Goldberg, Howard S. Wattanasin, Nich Murphy, Shawn N. TI Taking advantage of continuity of care documents to populate a research repository SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article DE Medical Informatics; Information Storage and Retrieval; Meaningful Use; Systems Integration; Database Management Systems ID DECISION-SUPPORT; HEALTH AB Objective Clinical data warehouses have accelerated clinical research, but even with available open source tools, there is a high barrier to entry due to the complexity of normalizing and importing data. The Office of the National Coordinator for Health Information Technology's Meaningful Use Incentive Program now requires that electronic health record systems produce standardized consolidated clinical document architecture (C-CDA) documents. Here, we leverage this data source to create a low volume standards based import pipeline for the Informatics for Integrating Biology and the Bedside (i2b2) clinical research platform. We validate this approach by creating a small repository at Partners Healthcare automatically from C-CDA documents. Materials and methods We designed an i2b2 extension to import C-CDAs into i2b2. It is extensible to other sites with variances in C-CDA format without requiring custom code. We also designed new ontology structures for querying the imported data. Results We implemented our methodology at Partners Healthcare, where we developed an adapter to retrieve C-CDAs from Enterprise Services. Our current implementation supports demographics, encounters, problems, and medications. We imported approximately 17 000 clinical observations on 145 patients into i2b2 in about 24 min. We were able to perform i2b2 cohort finding queries and view patient information through SMART apps on the imported data. Discussion This low volume import approach can serve small practices with local access to C-CDAs and will allow patient registries to import patient supplied C-CDAs. These components will soon be available open source on the i2b2 wiki. Conclusions Our approach will lower barriers to entry in implementing i2b2 where informatics expertise or data access are limited. C1 [Klann, Jeffrey G.; Mendis, Michael; Phillips, Lori C.; Goodson, Alyssa P.; Rocha, Beatriz H.; Goldberg, Howard S.; Wattanasin, Nich; Murphy, Shawn N.] Partners Healthcare, Boston, MA USA. [Klann, Jeffrey G.; Rocha, Beatriz H.; Goldberg, Howard S.; Murphy, Shawn N.] Harvard Univ, Sch Med, Boston, MA USA. [Klann, Jeffrey G.; Murphy, Shawn N.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Rocha, Beatriz H.; Goldberg, Howard S.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Klann, JG (reprint author), Massachusetts Gen Hosp, Comp Sci Lab, Constitut Ctr 1, Charlestown, MA 02129 USA. EM jeff.klann@mgh.harvard.edu FU ONC [90TR0001/01]; NIH National Library of Medicine [U54LM00874]; NIH NIGMS [5R01GM104303-02] FX This work was supported in part by ONC 90TR0001/01, NIH National Library of Medicine U54LM00874, and NIH NIGMS 5R01GM104303-02. NR 30 TC 3 Z9 4 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAR PY 2015 VL 22 IS 2 BP 370 EP 379 DI 10.1136/amiajnl-2014-003040 PG 10 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA CF7YE UT WOS:000352771500014 PM 25352566 ER PT J AU Nazi, KM Turvey, CL Klein, DM Hogan, TP Woods, SS AF Nazi, Kim M. Turvey, Carolyn L. Klein, Dawn M. Hogan, Timothy P. Woods, Susan S. TI VA OpenNotes: exploring the experiences of early patient adopters with access to clinical notes SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article DE access; patient portal; eHealth; Open Notes; communication; veteran ID PERSONAL HEALTH RECORDS; PATIENTS ONLINE ACCESS; MEDICAL-RECORDS; MEANINGFUL USE; OF-VETERANS; CARE; INFORMATION; PORTALS; DOCTORS; TRANSFORMATION AB Objective To explore the experience of early patient adopters who accessed their clinical notes online using the Blue Button feature of the My HealtheVet portal. Methods A web-based survey of VA patient portal users from June 22 to September 15, 2013. Results 33.5% of respondents knew that clinical notes could be viewed, and nearly one in four (23.5%) said that they had viewed their notes at least once. The majority of VA Notes users agreed that accessing their notes will help them to do a better job of taking medications as prescribed (80.1%) and be better prepared for clinic visits (88.6%). Nine out of 10 users agreed that use of visit notes will help them understand their conditions better (91.8%), and better remember the plan for their care (91.9%). In contrast, 87% disagreed that VA Notes will make them worry more, and 88.4% disagreed that access to VA Notes will be more confusing than helpful. Users who had either contacted their provider or healthcare team (11.9%) or planned to (13.5%) primarily wanted to learn more about a health issue, medication, or test results (53.7%). Conclusions Initial assessment of the patient experience within the first 9 months of availability provides evidence that patients both value and benefit from online access to clinical notes. These findings are congruent with OpenNotes study findings on a broader scale. Additional outreach and education is needed to enhance patient awareness. Healthcare professionals should author notes keeping in mind the opportunity patient access presents for enhanced communication. C1 [Nazi, Kim M.] US Dept Vet Affairs, Vet & Consumers Hlth Informat Off, Off Informat & Analyt, Vet Hlth Adm, Washington, DC USA. [Turvey, Carolyn L.; Klein, Dawn M.] Iowa City VA Hlth Care Syst, Comprehens Access & Delivery Res & Evaluat CADRE, Iowa City, IA USA. [Turvey, Carolyn L.; Klein, Dawn M.] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. [Hogan, Timothy P.] Edith Nourse Rogers Mem Vet Hosp, CHOIR, A VA HSR&D Ctr Innovat, Bedford, MA USA. [Hogan, Timothy P.] eHlth Qual Enhancement Res Initiat, Natl eHlth QUERI Coordinating Ctr, Edith Nourse Rogers Mem Vet Hosp, Bedford, MA USA. [Hogan, Timothy P.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Div Hlth Informat & Implementat Sci, Worcester, MA USA. [Woods, Susan S.] VA Maine Healthcare Syst, Togus, ME USA. [Woods, Susan S.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. RP Nazi, KM (reprint author), Vet & Consumers Hlth Informat Off, C-O 113 Holland Ave, Albany, NY 12208 USA. EM kim.nazi@va.gov FU Veterans Health Administration FX Primary funding source: Veterans Health Administration. NR 47 TC 14 Z9 14 U1 3 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAR PY 2015 VL 22 IS 2 BP 380 EP 389 DI 10.1136/amiajnl-2014-003144 PG 10 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA CF7YE UT WOS:000352771500015 PM 25352570 ER PT J AU Shah, AD Schmidt, H Sen, S Shlipak, MG Kanaya, AM AF Shah, Arti D. Schmidt, Heidi Sen, Saunak Shlipak, Michael G. Kanaya, Alka M. TI The association between body composition and cystatin C in South Asians: Results from the MASALA study SO OBESITY RESEARCH & CLINICAL PRACTICE LA English DT Article DE Body composition; Ectopic fat; Cystatin C; South Asian ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; ADIPOSE-TISSUE; SUBCUTANEOUS ADIPOSITY; DIABETES-MELLITUS; ATHEROSCLEROSIS; AMERICA; OBESITY; COHORT AB While South Asians have high rates of obesity and kidney disease, little is known about the effect of regional body composition on kidney function. We investigated the association between body composition measures and cystatin C-based estimated glomerular filtration rate (eGFR(cysC)) in 150 immigrant South Asians. The inverse association between overall adiposity and eGFR(cysC) was attenuated by C-reactive protein (CRP), while the association of ectopic fat was completely attenuated by metabolic covariates and CRP. In immigrant South Asians, the associations between overall adiposity and ectopic fat with decreased kidney function are largely explained by metabolic alterations and inflammation. (C) 2014 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved. C1 [Shah, Arti D.] Univ Calif San Francisco, Div Endocrinol & Metab, San Francisco, CA 94143 USA. [Schmidt, Heidi; Kanaya, Alka M.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA USA. [Sen, Saunak; Shlipak, Michael G.; Kanaya, Alka M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA USA. RP Kanaya, AM (reprint author), 2200 Post St,Suite C-428,POB 1222, San Francisco, CA 94115 USA. EM Arti.Shah@ucsf.edu FU NIH [K23 HL080026-01]; NIH/NCRR UCSF-CTSI Grant [UL1 RR024131]; T32 Training Grant [5T32DK007418]; Wilsey Family Foundation; [K24HL112827]; [RO1HL093009] FX This MASALA study was supported by the NIH [grant no. K23 HL080026-01] and by NIH/NCRR UCSF-CTSI Grant Number UL1 RR024131. Dr. Shah was supported by the T32 Training Grant Number 5T32DK007418 and the Wilsey Family Foundation. Dr. Kanaya was supported by K24HL112827 and RO1HL093009. NR 16 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1871-403X EI 1878-0318 J9 OBES RES CLIN PRACT JI Obes. Res. Clin. Pract. PD MAR-APR PY 2015 VL 9 IS 2 BP 180 EP 183 DI 10.1016/j.orcp.2014.10.221 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CG1XJ UT WOS:000353068500010 PM 25465493 ER PT J AU Carmona-Rubio, AE Lee, AM Puchner, S Ghoshhajra, B Sharma, UC AF Carmona-Rubio, Andres E. Lee, Ashley Mingshin Puchner, Stefan Ghoshhajra, Brian Sharma, Umesh C. TI A review of adherence to the guidelines for coronary CT angiography quantitative stenosis grading thresholds in published research SO POSTGRADUATE MEDICINE LA English DT Review DE Coronary artery disease; coronary artery stenosis; coronary computerized tomography angiography; noninvasive cardiac imaging ID COMPUTED-TOMOGRAPHY ANGIOGRAPHY; FRACTIONAL FLOW RESERVE; ACUTE CHEST-PAIN; INTERNATIONAL MULTICENTER REGISTRY; AMERICAN-HEART-ASSOCIATION; ARTERY CALCIUM SCORE; DUAL-SOURCE CT; MYOCARDIAL-PERFUSION; DIAGNOSTIC-ACCURACY; PROGNOSTIC VALUE AB Background: The degree of coronary stenosis of potential hemodynamic significance is central to the interpretation of coronary computed tomography angiography (CCTA), but has been variably defined in the literature. Societal guidelines have attempted to address this issue via recommended thresholds. Objectives: We surveyed the various thresholds for defining significant coronary stenosis reported in research published since the introduction of the Society for Cardiovascular Computed Tomography guidelines regarding the interpretation and reporting of CCTA. Methods: We systematically reviewed the results of bibliographic searches of all original research articles on CCTA, focusing on studies reporting > 25 subjects, to assess the definitions of severity of coronary lesions as found on CCTA. To enable comparisons, we stratified the methods of reporting lesion severity into >= 50%, 50% to 69%, and "others" (including infrequent reporting methods). Results: Fifty-nine11 published studies were identified and met inclusion criteria. Eighteen studies reported the severity of coronary stenosis using a definition of 50% to 69% as moderate stenosis; 35 studies defined >= 50% coronary stenosis as "stenosis," "significant stenosis," or "obstructive lesion" without distinguishing a threshold for moderate versus severe stenosis. Six studies utilized other thresholds, such as 20% to 75%, 40% to 69%, 40% to 70%, 40% to 79%, and 50% to 75% to define moderate coronary stenosis. Conclusions: Fifty-three of 59 studies were graded in accordance with the recommended threshold of >= 50% defining potentially significant stenosis, with 18 studies reporting precisely in accordance with the guidelines-recommended thresholds of >= 50% narrowing as defining moderate stenosis and >= 70% narrowing as defining severe stenosis. Six studies were reported using alternative thresholds for significant stenosis. However, a majority of research studies published since 2009 do not follow the societal guidelines for stenosis grading, since these studies do not clearly describe the degree of coronary stenosis. C1 [Carmona-Rubio, Andres E.] SUNY Buffalo, Sch Med, Dept Med, Buffalo, NY 14260 USA. [Lee, Ashley Mingshin; Puchner, Stefan; Ghoshhajra, Brian; Sharma, Umesh C.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Cardiac MR PET CT Program, Boston, MA 02115 USA. RP Carmona-Rubio, AE (reprint author), Erie Cty Med Ctr & Labs, David K Miller Bldg,462 Grider St, Buffalo, NY 14215 USA. EM andresca@buffalo.edu NR 85 TC 1 Z9 1 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0032-5481 EI 1941-9260 J9 POSTGRAD MED JI Postgrad. Med. PD MAR PY 2015 VL 127 IS 2 BP 194 EP 201 DI 10.1080/00325481.2015.995065 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CG7AB UT WOS:000353453200010 PM 25540988 ER PT J AU Wan, ZM Li, GA AF Wan, Zongmiao Li, Guoan TI X-Stop (R) Implantation Effectively Limits Segmental Lumbar Extension in-vivo without Altering the Kinematics of the Adjacent Levels SO TURKISH NEUROSURGERY LA English DT Article DE Interspinous process distracting device; In-vivo; Kinematics; Adjacent segments ID NEUROGENIC INTERMITTENT CLAUDICATION; INTERSPINAL PROCESS DECOMPRESSION; X-STOP DEVICE; SPINAL STENOSIS; DEGENERATION; BIOMECHANICS; FLEXIBILITY; MULTICENTER; FUSION; MOTION AB AIM: To evaluate the in-vivo three-dimensional (3D) vertebral kinematics of the implanted and adjacent segments after implantation of the interspinous process distracting (ISP) device during various functional activities. MATERIAL and METHODS: Eight patients with lumbar spinal stenosis (LSS) scheduled for X-Stop (R) surgery were recruited. Prior to surgery, patients were scanned with computed tomography/magnetic resonance imaging (CT/MRI) in order to construct 3D L2 to 51 vertebral models. The lumbar spines of the patients were then imaged using two fluoroscopes while they performed seven functional activities before and after X-Stop (R) surgeries. The in-vivo 3D vertebral positions were determined in the dual fluoroscopic images using an established 2D-3D matching method.The vertebral 3D ranges of motion (ROM) of the implanted and cranial-caudal adjacent levels were then measured. RESULTS: Primary ROMs of the implanted segments were significantly decreased (p<0.05) by 50.2% only at torso extension, from preoperative 2.5 +/- 1.4 degrees to postoperative 1.1 +/- 0.5 degrees, but not significantly (p>0.05) at flexion, twisting and lateral bending. Primary ROM and the coupled translations and rotations of the implanted and the adjacent levels were not significantly changed during each posture. CONCLUSION: X-Stop (R) implantation reduced the in-vivo range of extension by 50.2% at the implanted segment without disturbing 3D kinematics at the adjacent segments. C1 [Wan, Zongmiao] Nanchang Univ, Affiliated Hosp 1, Dept Orthopaed, Nanchang, Jiangxi, Peoples R China. [Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed, Boston, MA USA. RP Wan, ZM (reprint author), Nanchang Univ, Affiliated Hosp 1, Dept Orthopaed, Nanchang, Jiangxi, Peoples R China. EM zongmiao2008@gmail.com NR 26 TC 0 Z9 0 U1 0 U2 1 PU TURKISH NEUROSURGICAL SOC PI BAHCELIEVLER PA TASKENT CADDESI 13-4, BAHCELIEVLER, ANKARA 06500, TURKEY SN 1019-5149 J9 TURK NEUROSURG JI Turk. Neurosurg. PD MAR PY 2015 VL 25 IS 2 BP 279 EP 284 DI 10.5137/1019-5149.JTN.10135-13.0 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CG0AH UT WOS:000352928500014 PM 26014013 ER PT J AU Dunn, IF Chiocca, EA AF Dunn, Ian F. Chiocca, E. Antonio TI Academic Productivity in Today's Training Climate: A Fellowship's impact SO WORLD NEUROSURGERY LA English DT Editorial Material DE Academic productivity; Academic promotion; Academic rank; H-index; Neurological surgery fellowships; Neurological surgery fellowship training; Neurological surgery; Scholarly impact; Scholarly productivity C1 [Dunn, Ian F.; Chiocca, E. Antonio] Harvard Univ, Sch Med, Dept Neurosurg, Inst Neurosci,Brigham & Womens Faulkner Hosp, Boston, MA 02163 USA. [Chiocca, E. Antonio] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Chiocca, EA (reprint author), Harvard Univ, Sch Med, Dept Neurosurg, Inst Neurosci,Brigham & Womens Faulkner Hosp, Boston, MA 02163 USA. EM EAChiocca@partners.org NR 0 TC 1 Z9 1 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 MAR PY 2015 VL 83 IS 3 BP 328 EP 329 DI 10.1016/j.wneu.2014.10.060 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CG1MN UT WOS:000353036900022 PM 24176836 ER PT J AU Abd-El-Barr, MM Chiocca, EA AF Abd-El-Barr, Muhammad M. Chiocca, E. Antonio TI No Free Lunch: Secondary Neoplasms After Stereotactic Radiation SO WORLD NEUROSURGERY LA English DT Editorial Material DE Dedifferentiation; Late complications; Malignant transformation; Secondary neoplasm; Stereotactic radiosurgery ID ARTERIOVENOUS-MALFORMATIONS; RADIOSURGERY; RADIOTHERAPY; RESECTION; GLIOMAS; BRAIN; RISK C1 [Chiocca, E. Antonio] Harvard Univ, Sch Med, Dept Neurosurg, Inst Neurosci,Brigham & Womens Faulkner Hosp, Boston, MA 02163 USA. Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Chiocca, EA (reprint author), Harvard Univ, Sch Med, Dept Neurosurg, Inst Neurosci,Brigham & Womens Faulkner Hosp, Boston, MA 02163 USA. EM EAChiocca@partners.org NR 15 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 MAR PY 2015 VL 83 IS 3 BP 330 EP 331 DI 10.1016/j.wneu.2014.02.016 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CG1MN UT WOS:000353036900023 PM 24534062 ER PT J AU Carpenter, GSJ Carpenter, TP Kimbrel, NA Flynn, EJ Pennington, ML Cammarata, C Zimering, RT Kamholz, BW Gulliver, SB AF Carpenter, Grace Stephanie J. Carpenter, Thomas P. Kimbrel, Nathan A. Flynn, Elisa J. Pennington, Michelle L. Cammarata, Claire Zimering, Rose T. Kamholz, Barbara W. Gulliver, Suzy B. TI Social Support, Stress, and Suicidal Ideation in Professional Firefighters SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article DE suicidal ideation; social support; stress; firefighters ID POSTTRAUMATIC-STRESS; OCCUPATIONAL STRESS; LIFE STRESS; DEPRESSIVE SYMPTOMS; RISK-FACTORS; FOLLOW-UP; BEHAVIOR; HOPELESSNESS; DISORDER; MODEL AB Objective: To hypothesize that social support may protect against the effect of firefighter stress on suicidal ideation. Methods: Overall, 334 firefighters completed measures of occupational stress, social support, and suicidal ideation. Results: At high levels of social support, no association was observed between occupational stress and suicidal ideation (phi = -.06, ns); however, when social support was low, occupational stress showed a positive association with suicidal ideation (phi = .16, p < .05). Conclusions: The association between occupational stress and suicidal ideation may be reduced by social support. Further research on this topic is warranted. C1 [Carpenter, Grace Stephanie J.; Flynn, Elisa J.; Pennington, Michelle L.; Gulliver, Suzy B.] Baylor Scott & White Warriors Res Inst, Waco, TX 76708 USA. [Carpenter, Thomas P.] Seattle Pacific Univ, Seattle, WA 98119 USA. [Kimbrel, Nathan A.] Durham Vet Affairs VA Med Ctr, Durham, NC USA. [Cammarata, Claire] New York City Fire Dept Counseling Serv Unit, New York, NY USA. [Zimering, Rose T.; Kamholz, Barbara W.] VA Boston Healthcare Syst, Outpatient Mental Hlth, Boston, MA USA. RP Gulliver, SB (reprint author), Baylor Scott & White Warriors Res Inst, Waco, TX 76708 USA. EM suzybird@aol.com RI Kimbrel, Nathan/P-3109-2016 OI Kimbrel, Nathan/0000-0001-7218-1005 FU FEMA Award [EMW2010FP00597]; NIMH R21 Award [1R21M-H06458401A2]; Career Development Award-2 from the Clinical Science Research and Development Service of the VA Office of Research and Development [1IK-2CX000525-01A1] FX This research was supported by a FEMA Award (EMW2010FP00597) entitled "Motivational intervention to maximize peer behavioral health awareness and skills" and a NIMH R21 Award (1R21M-H06458401A2) "Developing group treatments for acute stress disorder." The third author was supported by a Career Development Award-2 (1IK-2CX000525-01A1) from the Clinical Science Research and Development Service of the VA Office of Research and Development. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 40 TC 7 Z9 7 U1 9 U2 15 PU PNG PUBLICATIONS PI OAK RIDGE PA 2205-K OAK RIDGE RD, #115, OAK RIDGE, NC 27310 USA SN 1945-7359 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD MAR PY 2015 VL 39 IS 2 BP 191 EP 196 DI 10.5993/AJHB.39.2.5 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CF4SS UT WOS:000352542300005 PM 25564831 ER PT J AU Rao, DR Sordillo, JE Kopel, LS Gaffin, JM Sheehan, WJ Hoffman, E Ozonoff, A Gold, DR Phipatanakul, W AF Rao, Devika R. Sordillo, Joanne E. Kopel, Lianne S. Gaffin, Jonathan M. Sheehan, William J. Hoffman, Elaine Ozonoff, Al Gold, Diane R. Phipatanakul, Wanda TI Association between allergic sensitization and exhaled nitric oxide in children in the School Inner-City Asthma Study SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Letter ID ATOPY; AGE C1 [Rao, Devika R.] Univ Texas SW Med Ctr Dallas, Div Resp Med, Dallas, TX 75390 USA. [Sordillo, Joanne E.; Gold, Diane R.; Phipatanakul, Wanda] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Kopel, Lianne S.; Gaffin, Jonathan M.] Div Resp Dis, Boston, MA USA. [Sheehan, William J.; Phipatanakul, Wanda] Div Allergy & Immunol, Boston, MA USA. [Kopel, Lianne S.; Gaffin, Jonathan M.; Sheehan, William J.; Phipatanakul, Wanda] Boston Childrens Hosp, Boston, MA USA. [Kopel, Lianne S.; Gaffin, Jonathan M.; Sheehan, William J.; Hoffman, Elaine; Gold, Diane R.; Phipatanakul, Wanda] Harvard Univ, Sch Med, Boston, MA USA. [Hoffman, Elaine] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Ozonoff, Al] Boston Childrens Hosp, Ctr Patient Safety & Qual Res, Boston, MA USA. [Ozonoff, Al] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Rao, DR (reprint author), Univ Texas SW Med Ctr Dallas, Div Resp Med, Dallas, TX 75390 USA. EM wanda.phipatanakul@childrens.harvard.edu FU NCATS NIH HHS [UL1 TR001102]; NHLBI NIH HHS [U10 HL098102, U10 HL 098102]; NIAID NIH HHS [K23 AI106945, K23 AI104780, R01 AI 073964,, R01 AI073964, K24 AI106822, K24 AI 106822, R01 AI 073964-02S1, K23 AI 106945] NR 11 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 EI 1534-4436 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD MAR PY 2015 VL 114 IS 3 BP 256 EP 257 DI 10.1016/j.anai.2014.12.004 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA CF1ML UT WOS:000352309800027 PM 25595887 ER PT J AU Rao, DR Sordillo, JE Kopel, LS Gaffin, JM Sheehan, WJ Hoffman, E Ozonoff, A Gold, DR Phipatanakul, W AF Rao, Devika R. Sordillo, Joanne E. Kopel, Lianne S. Gaffin, Jonathan M. Sheehan, William J. Hoffman, Elaine Ozonoff, Al Gold, Diane R. Phipatanakul, Wanda TI Eosinophilic esophagitis associated with Cynanchum wilfordii SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Letter ID EXHALED NITRIC-OXIDE; CHILDREN; ASTHMA; SENSITIZATION; ALLERGEN; ATOPY; AGE C1 [Rao, Devika R.] Univ Texas SW Med Ctr Dallas, Div Resp Med, Dallas, TX 75390 USA. [Sordillo, Joanne E.; Gold, Diane R.; Phipatanakul, Wanda] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Kopel, Lianne S.; Gaffin, Jonathan M.] Div Resp Dis, Boston, MA USA. [Sheehan, William J.; Phipatanakul, Wanda] Div Allergy & Immunol, Boston, MA USA. [Kopel, Lianne S.; Gaffin, Jonathan M.; Sheehan, William J.; Phipatanakul, Wanda] Boston Childrens Hosp, Boston, MA USA. [Kopel, Lianne S.; Gaffin, Jonathan M.; Sheehan, William J.; Hoffman, Elaine; Gold, Diane R.; Phipatanakul, Wanda] Harvard Univ, Sch Med, Boston, MA USA. [Hoffman, Elaine] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Ozonoff, Al] Boston Childrens Hosp, Ctr Patient Safety & Qual Res, Boston, MA USA. [Ozonoff, Al] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Rao, DR (reprint author), Univ Texas SW Med Ctr Dallas, Div Resp Med, Dallas, TX 75390 USA. EM wanda.phipatanakul@childrens.harvard.edu OI Park, Hae-Sim/0000-0003-2614-0303 NR 11 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 1081-1206 EI 1534-4436 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD MAR PY 2015 VL 114 IS 3 BP 257 EP + DI 10.1016/j.anai.2014.12.010 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA CF1ML UT WOS:000352309800028 ER PT J AU Shields, RK Nguyen, MH Potoski, BA Press, EG Chen, L Kreiswirth, BN Clarke, LG Eschenauer, GA Clancy, CJ AF Shields, Ryan K. Nguyen, M. Hong Potoski, Brian A. Press, Ellen G. Chen, Liang Kreiswirth, Barry N. Clarke, Lloyd G. Eschenauer, Gregory A. Clancy, Cornelius J. TI Doripenem MICs and ompK36 Porin Genotypes of Sequence Type 258, KPC-Producing Klebsiella pneumoniae May Predict Responses to Carbapenem-Colistin Combination Therapy among Patients with Bacteremia SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CRITICALLY-ILL PATIENTS; RESISTANT; ENTEROBACTERIACEAE; MORTALITY AB Treatment failures of a carbapenem-colistin regimen among patients with bacteremia due to sequence type 258 (ST258), KPC-2-producing Klebsiella pneumoniae were significantly more likely if both agents were inactive in vitro, as defined by a colistin MIC of >2 mu g/ml and the presence of either a major ompK36 porin mutation (guanine and alanine insertions at amino acids 134 and 135 [ins aa 134-135 GD], IS5 promoter insertion [P = 0.007]) or a doripenem MIC of >8 mu g/ml (P = 0.01). Major ompK36 mutations among KPC-K. pneumoniae strains are important determinants of carbapenem-colistin responses in vitro and in vivo. C1 [Shields, Ryan K.; Nguyen, M. Hong; Press, Ellen G.; Clancy, Cornelius J.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Shields, Ryan K.; Nguyen, M. Hong; Potoski, Brian A.; Clarke, Lloyd G.; Eschenauer, Gregory A.] Univ Pittsburgh, Med Ctr, Antibiot Management Program, Pittsburgh, PA USA. [Shields, Ryan K.; Nguyen, M. Hong; Clancy, Cornelius J.] Univ Pittsburgh, Med Ctr, XDR Pathogen Lab, Pittsburgh, PA USA. [Chen, Liang; Kreiswirth, Barry N.] Rutgers State Univ, New Jersey Med Sch, Publ Hlth Res Inst, Newark, NJ 07102 USA. [Eschenauer, Gregory A.] Univ Pittsburgh, Med Ctr, Dept Pharm, Pittsburgh, PA USA. [Potoski, Brian A.] Univ Pittsburgh, Dept Pharm & Therapeut, Pittsburgh, PA USA. [Clancy, Cornelius J.] VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. RP Nguyen, MH (reprint author), Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. EM mhn5@pitt.edu FU University of Pittsburgh Medical Center; National Center for Advanced Translational Sciences of the National Institutes of Health (NIH) [KL2 RR024154] FX This project was supported by funding provided to the XDR Pathogen Laboratory by the University of Pittsburgh Medical Center and by the National Center for Advanced Translational Sciences of the National Institutes of Health (NIH) under award no. KL2 RR024154 given to R.K.S. NR 15 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 2015 VL 59 IS 3 BP 1505 EP 1509 DI 10.1128/AAC.03894-14 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA CF4VF UT WOS:000352550000016 PM 25534733 ER PT J AU Van Laar, TA Chen, T You, T Leung, KP AF Van Laar, Tricia A. Chen, Tsute You, Tao Leung, Kai P. TI Sublethal Concentrations of Carbapenems Alter Cell Morphology and Genomic Expression of Klebsiella pneumoniae Biofilms SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; LARGE GENE LISTS; ESCHERICHIA-COLI; PSEUDOMONAS-AERUGINOSA; SUBINHIBITORY CONCENTRATIONS; MOLECULAR-MECHANISMS; IN-VIVO; ANTIBIOTICS; IMIPENEM; DNA AB Klebsiella pneumoniae, a Gram-negative bacterium, is normally associated with pneumonia in patients with weakened immune systems. However, it is also a prevalent nosocomial infectious agent that can be found in infected surgical sites and combat wounds. Many of these clinical strains display multidrug resistance. We have worked with a clinical strain of K. pneumoniae that was initially isolated from a wound of an injured soldier. This strain demonstrated resistance to many commonly used antibiotics but sensitivity to carbapenems. This isolate was capable of forming biofilms in vitro, contributing to its increased antibiotic resistance and impaired clearance. We were interested in determining how sublethal concentrations of carbapenem treatment specifically affect K. pneumoniae biofilms both in morphology and in genomic expression. Scanning electron microscopy showed striking morphological differences between untreated and treated biofilms, including rounding, blebbing, and dimpling of treated cells. Comparative transcriptome analysis using RNA sequencing (RNA-Seq) technology identified a large number of open reading frames (ORFs) differentially regulated in response to carbapenem treatment at 2 and 24 h. ORFs upregulated with carbapenem treatment included genes involved in resistance, as well as those coding for antiporters and autoinducers. ORFs downregulated included those coding for metal transporters, membrane biosynthesis proteins, and motility proteins. Quantitative real-time PCR validated the general trend of some of these differentially regulated ORFs. Treatment of K. pneumoniae biofilms with sublethal concentrations of carbapenems induced a wide range of phenotypic and gene expression changes. This study reveals some of the mechanisms underlying how sublethal amounts of carbapenems could affect the overall fitness and pathogenic potential of K. pneumoniae biofilm cells. C1 [Van Laar, Tricia A.; You, Tao; Leung, Kai P.] US Army Dent & Trauma Res Detachment, Microbiol Branch, Inst Surg Res, Jbsa Ft Sam Houston, TX 78234 USA. [Chen, Tsute] Forsyth Inst, Cambridge, MA USA. RP Leung, KP (reprint author), US Army Dent & Trauma Res Detachment, Microbiol Branch, Inst Surg Res, Jbsa Ft Sam Houston, TX 78234 USA. EM kai.p.leung.civ@mail.mil OI Van Laar, Tricia/0000-0002-4654-8501 FU U.S. Army Medical Research and Materiel Command, Combat Casualty Care Research Directorate; Research Associateship Program from the National Research Council FX This work was supported by the U.S. Army Medical Research and Materiel Command, Combat Casualty Care Research Directorate and the Research Associateship Program from the National Research Council (T.A.V.L.). NR 67 TC 4 Z9 4 U1 1 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 2015 VL 59 IS 3 BP 1712 EP 1722 DI 10.1128/AAC.04581-14 PG 11 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA CF4VF UT WOS:000352550000042 PM 25583711 ER PT J AU Jayamani, E Rajamuthiah, R Larkins-Ford, J Fuchs, BB Conery, AL Vilcinskas, A Ausubel, FM Mylonakis, E AF Jayamani, Elamparithi Rajamuthiah, Rajmohan Larkins-Ford, Jonah Fuchs, Beth Burgwyn Conery, Annie L. Vilcinskas, Andreas Ausubel, Frederick M. Mylonakis, Eleftherios TI Insect-Derived Cecropins Display Activity against Acinetobacter baumannii in a Whole-Animal High-Throughput Caenorhabditis elegans Model SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INFECTIOUS-DISEASES-SOCIETY; HOST GALLERIA-MELLONELLA; ANTIMICROBIAL PEPTIDES; POLYMYXIN-B; VIRULENCE FACTORS; ESCHERICHIA-COLI; DEFENSE PEPTIDES; INDUCIBLE GENES; DRUG DISCOVERY; NO ESKAPE AB The rise of multidrug-resistant Acinetobacter baumannii and a concomitant decrease in antibiotic treatment options warrants a search for new classes of antibacterial agents. We have found that A. baumannii is pathogenic and lethal to the model host organism Caenorhabditis elegans and have exploited this phenomenon to develop an automated, high-throughput, high-content screening assay in liquid culture that can be used to identify novel antibiotics effective against A. baumannii. The screening assay involves coincubating C. elegans with A. baumannii in 384-well plates containing potential antibacterial compounds. At the end of the incubation period, worms are stained with a dye that stains only dead animals, and images are acquired using automated microscopy and then analyzed using an automated image analysis program. This robust assay yields a Z' factor consistently greater than 0.7. In a pilot experiment to test the efficacy of the assay, we screened a small custom library of synthetic antimicrobial peptides (AMPs) that were synthesized using publicly available sequence data and/or transcriptomic data from immune-challenged insects. We identified cecropin A and 14 other cecropin or cecropin-like peptides that were able to enhance C. elegans survival in the presence of A. baumannii. Interestingly, one particular hit, BR003-cecropin A, a cationic peptide synthesized by the mosquito Aedes aegypti, showed antibiotic activity against a panel of Gram-negative bacteria and exhibited a low MIC (5 mu g/ml) against A. baumannii. BR003-cecropin A causes membrane permeability in A. baumannii, which could be the underlying mechanism of its lethality. C1 [Jayamani, Elamparithi; Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Mylonakis, Eleftherios] Brown Univ, Rhode Isl Hosp, Div Infect Dis, Alpert Med Sch, Providence, RI 02903 USA. [Jayamani, Elamparithi; Rajamuthiah, Rajmohan; Larkins-Ford, Jonah; Fuchs, Beth Burgwyn; Conery, Annie L.; Ausubel, Frederick M.; Mylonakis, Eleftherios] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Vilcinskas, Andreas] Univ Giessen, Inst Phytopathol & Appl Zool, D-35390 Giessen, Germany. RP Mylonakis, E (reprint author), Brown Univ, Rhode Isl Hosp, Div Infect Dis, Alpert Med Sch, Providence, RI 02903 USA. EM emylonakis@lifespan.org FU NIH [R01 AI085581] FX We acknowledge NIH grant R01 AI085581. NR 76 TC 8 Z9 8 U1 2 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 2015 VL 59 IS 3 BP 1733 EP 1742 DI 10.1128/AAC.04198-14 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA CF4VF UT WOS:000352550000044 PM 25583713 ER PT J AU Jung, M Choi, M Lee, TR AF Jung, Minsoo Choi, Mankyu Lee, Tae-Ro TI Determinants of Public Phobia About Infectious Diseases in South Korea: Effect of Health Communication and Gender Difference SO ASIA-PACIFIC JOURNAL OF PUBLIC HEALTH LA English DT Article DE risk perception; disease phobia; bovine spongiform encephalopathy; highly pathogenic avian influenza; mass media; health communication ID MAD-COW-DISEASE; RISK PERCEPTION; SARS; MEDIA; REPRESENTATIONS; MANAGEMENT; EPIDEMIC; BELIEFS AB This study investigated the individual and social determinants of the public's phobia of infectious diseases in South Korea, where collective action was recently fueled by the public phobia over mad cow disease (bovine spongiform encephalopathy [BSE]). Gender-specific multivariate regression was used to compare the public perception of BSE and highly pathogenic avian influenza (HPAI). The analysis results differentiated between the determinants of the phobia for the 2 diseases, BSE and HPAI (N = 1002). As with HIV/AIDS and leprosy, the public fear of HPAI was expressed as a disease phobia that seeks to ensure the social exclusion of infection sources, whereas the fear of BSE was influenced by social and communication factors. Therefore, BSE, unlike previous HPAI, can be rapidly amplified amid the growing distrust in health communication, in which case the social determinants of disease phobia are associated with communicator trust, social values, and political attitude toward diseases rather than disease perception. C1 [Jung, Minsoo] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Jung, Minsoo] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. [Choi, Mankyu; Lee, Tae-Ro] Korea Univ, Dept Healthcare Management, Seoul, South Korea. RP Jung, M (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 450 Brookline Ave,LW 601, Boston, MA 02215 USA. EM minsoo_jung@dfci.harvard.edu OI Jung, Minsoo/0000-0003-3317-6507 FU National Research Foundation of Korea - Korean Government [NRF-2011-357-E00028] FX This work was supported by National Research Foundation of Korea Grant funded by the Korean Government (NRF-2011-357-E00028) to Dr Minsoo Jung (principal investigator). NR 30 TC 0 Z9 0 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1010-5395 EI 1941-2479 J9 ASIA-PAC J PUBLIC HE JI Asia-Pac. J. Public Health PD MAR PY 2015 VL 27 IS 2 BP NP833 EP NP843 DI 10.1177/1010539513475653 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CF5GT UT WOS:000352586200082 PM 23430887 ER PT J AU Ventz, S Trippa, L AF Ventz, Steffen Trippa, Lorenzo TI Bayesian Designs and the Control of Frequentist Characteristics: A Practical Solution SO BIOMETRICS LA English DT Article DE Bayesian design; Clinical trials; Decision theory; Frequentist constraints ID DECISION-THEORETIC DESIGNS; CLINICAL-TRIALS; POWER AB Frequentist concepts, such as the control of the type I error or the false discovery rate, are well established in the medical literature and often required by regulators. Most Bayesian designs are defined without explicit considerations of frequentist characteristics. Once the Bayesian design is structured, statisticians use simulations and adjust tuning parameters to comply with a set of targeted operating characteristics. These adjustments affect the use of prior information and utility functions. Here we consider a Bayesian decision theoretic approach for experimental designs with explicit frequentist requisites. We define optimal designs under a set of constraints required by a regulator. Our approach combines the use of interpretable utility functions with frequentist criteria, and selects an optimal design that satisfies a set of required operating characteristics. We illustrate the approach using a group-sequential multi-arm Phase II trial and a bridging trial. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Ventz, S (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Dana Farber Canc Inst, 665 Huntington Ave, Boston, MA 02115 USA. EM steffen@jimmy.harvard.edu NR 36 TC 2 Z9 2 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD MAR PY 2015 VL 71 IS 1 BP 218 EP 226 DI 10.1111/biom.12226 PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA CF5GO UT WOS:000352585700024 PM 25196832 ER PT J AU Kushwaha, D O'Leary, C Cron, KR Deraska, P Zhu, KY D'Andrea, AD Kozono, D AF Kushwaha, Deepa O'Leary, Colin Cron, Kyle R. Deraska, Peter Zhu, Kaya D'Andrea, Alan D. Kozono, David TI USP9X inhibition promotes radiation-induced apoptosis in non-small cell lung cancer cells expressing mid-to-high MCL1 SO CANCER BIOLOGY & THERAPY LA English DT Article DE apoptosis; lung cancer; MCL1; radiosensitizing agents; RNAi screen; USP9X; DUB; deubiquitinase; IR; ionizing radiation; NSCLC; non-small cell lung cancer; RT; radiotherapy; shRNA; short hairpin RNA; siRNA; small interfering RNA (siRNA) ID PANCREATIC DUCTAL ADENOCARCINOMA; DEUBIQUITINATING ENZYMES; FAM/USP9X AB Background and Purpose: Radiotherapy (RT) is vital for the treatment of locally advanced non-small cell lung cancer (NSCLC), yet its delivery is limited by tolerances of adjacent organs. We sought therefore to identify and characterize gene targets whose inhibition may improve RT. Materials and Methods: Whole genome pooled shRNA cytotoxicity screens were performed in A549 and NCI-H460 using a retroviral library of 74,705 sequences. Cells were propagated with or without daily radiation Monday-Friday. Radiosensitization by top differential dropout hits was assessed by clonogenic assays. Apoptosis was assessed using a caspase 3/7 cell-based activity assay and by annexin V-FITC and PI staining. MCL1 expression was assessed by qPCR and Western blotting. Results: USP9X, a deubiquitinase, was a top hit among druggable gene products. WP1130, a small molecule USP9X inhibitor, showed synergistic cytotoxicity with IR. MCL1, an anti-apoptotic protein deubiquitinated by USP9X, decreased with USP9X inhibition and IR. This was accompanied by increases in caspase 3/7 activity and apoptosis. In a panel of NSCLC lines, MCL1 and USP9X protein and gene expression levels were highly correlated. Lines showing high levels of MCL1 expression were the most sensitive to USP9X inhibition. Conclusions: These data support the use of MCL1 expression as a predictive biomarker for USP9X inhibitors in NSCLC therapy. C1 [Kushwaha, Deepa; O'Leary, Colin; Cron, Kyle R.; Deraska, Peter; Zhu, Kaya; D'Andrea, Alan D.; Kozono, David] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [D'Andrea, Alan D.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Kozono, D (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. EM dkozono@lroc.harvard.edu FU American Society for Radiation Oncology (ASTRO); Joint Center for Radiation Therapy Foundation; Dana-Farber/Harvard Cancer Center SPORE Developmental Research Project Award in Lung Cancer Research; National Cancer Institute of the National Institutes of Health [K08CA172354] FX DK is supported by the American Society for Radiation Oncology (ASTRO) Junior Faculty Career Research Training Award, a Joint Center for Radiation Therapy Foundation Grant, a Dana-Farber/Harvard Cancer Center SPORE Developmental Research Project Award in Lung Cancer Research and the National Cancer Institute of the National Institutes of Health under Award Number K08CA172354. NR 26 TC 4 Z9 5 U1 1 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAR PY 2015 VL 16 IS 3 BP 392 EP 401 DI 10.1080/15384047.2014.1002358 PG 10 WC Oncology SC Oncology GA CF5OQ UT WOS:000352607000006 PM 25692226 ER PT J AU Paul, S Goyal, A Duncan, LM Smith, GP AF Paul, Suchismita Goyal, Amrita Duncan, Lyn M. Smith, Gideon P. TI Granulomatous reaction to liquid injectable silicone for gluteal enhancement: review of management options and success of doxycycline SO DERMATOLOGIC THERAPY LA English DT Article DE doxycycline; granuloma; liquid silicone; mycobacterial infection ID SOFT-TISSUE AUGMENTATION AB Liquid injectable silicone (LIS) for cosmetic purposes has been widely available and commonly used for almost half a century. An increase in buttock augmentation procedures because of patients wanting to emulate the look of some celebrities has recently highlighted cases in the media of unsafe administration of liquid silicone injections. Severe complications including death have been reported. In this article, we report a case in which liquid silicone was injected in the patient's gluteal tissue resulting in granulomatous reactions in the surrounding tissues. The patient responded well to doxycycline, presumably because of both its antimicrobial properties and immunomodulatory effects. C1 [Paul, Suchismita; Goyal, Amrita] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Duncan, Lyn M.] Massachusetts Gen Hosp, Pathol Serv, Dermatopathol Unit, Boston, MA 02114 USA. [Smith, Gideon P.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Paul, S (reprint author), Harvard Univ, Sch Med, 25 Shattuck St, Boston, MA 02115 USA. EM suchismita_paul@hms.harvard.edu NR 15 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1396-0296 EI 1529-8019 J9 DERMATOL THER JI Dermatol. Ther. PD MAR-APR PY 2015 VL 28 IS 2 BP 98 EP 101 DI 10.1111/dth.12204 PG 4 WC Dermatology SC Dermatology GA CF5XO UT WOS:000352630800012 PM 25649644 ER PT J AU Cury, RC Kitt, TM Feaheny, K Blankstein, R Ghoshhajra, BB Budoff, MJ Leipsic, J Min, JK Akin, J George, RT AF Cury, Ricardo C. Kitt, Therese M. Feaheny, Kathleen Blankstein, Ron Ghoshhajra, Brian B. Budoff, Matthew J. Leipsic, Jonathon Min, James K. Akin, Jamie George, Richard T. TI A randomized, multicenter, multivendor study of myocardial perfusion imaging with regadenoson CT perfusion vs single photon emission CT SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Regadenoson; CT perfusion; Myocardial ischemia; Single photon emission CT ID CORONARY-ARTERY-DISEASE; INCREMENTAL PROGNOSTIC VALUE; COMPUTED TOMOGRAPHIC ANGIOGRAPHY; DIAGNOSTIC PERFORMANCE; MULTIDETECTOR CT; MEDICAL THERAPY; ADENOSINE; ISCHEMIA; REVASCULARIZATION; SPECT AB Background: Myocardial CT perfusion (CTP) is a promising tool for the detection of myocardial ischemia. We hypothesize that regadenoson CTP is noninferior to regadenoson single photon emission CT (SPECT) for detecting or excluding myocardial ischemia. Methods: Patients (men >= 45 years; women >= 50 years) with known or suspected coronary artery disease (n = 124) were randomized to 1 of 2 diagnostic sequences: rest and regadenoson SPECT on day 1, then regadenoson CTP and rest CTP (and coronary CT angiography [CTA]) (CTA; same acquisition) on day 2 or regadenoson CTP and rest CTP (and CTA) on Day 1, then rest and regadenoson SPECT on day 2. Scanning platforms included 64-, 128-, 256-, and 320-slice systems. The primary analysis examined the agreement rate between CTP and SPECT for detecting or excluding reversible ischemia in >= 2 myocardial segments as assessed by independent, blinded readers. Results: Complete and interpretable CTP and SPECT scans were obtained for 110 patients. Regadenoson CTP was noninferior to SPECT for detecting or excluding reversible ischemia with an agreement rate of 0.87 (95% confidence interval [CI], 0.77-0.97) and sensitivity and specificity of 0.90 (95% CI, 0.71-1.00) and 0.84 (95% CI, 0.77-0.91), respectively. The agreement rate for detecting or excluding >= 1 fixed defects by regadenoson CTP and SPECT was 0.86 (95% CI, 0.74-0.98). With SPECT as the reference standard, the diagnostic accuracies for detecting or excluding ischemia by regadenoson CTP and CTA alone were 0.85 (95% CI, 0.78-0.91) and 0.69 (95% CI, 0.60-0.77), respectively. Conclusions: This study establishes the noninferiority of regadenoson CTP to SPECT for detecting or excluding myocardial ischemia. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Cury, Ricardo C.] Baptist Hosp Miami, Dept Radiol, Miami, FL 33176 USA. [Cury, Ricardo C.] Miami Cardiac & Vasc Inst, Miami, FL USA. [Kitt, Therese M.] Astellas Sci & Med Affairs Inc, Northbrook, IL USA. [Feaheny, Kathleen; Akin, Jamie] Astellas Pharrna Global Dev Inc, Northbrook, IL USA. [Blankstein, Ron] Brigham & Womens Hosp, Dept Radiol, Div Cardiovasc, Boston, MA 02115 USA. [Blankstein, Ron; Ghoshhajra, Brian B.] Harvard Univ, Sch Med, Boston, MA USA. [Ghoshhajra, Brian B.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Budoff, Matthew J.] Harbor UCLA, Med Ctr, Dept Med, Los Angeles, CA USA. [Leipsic, Jonathon] St Pauls Hosp, Dept Med Imaging, Div Cardiol, Vancouver, BC V6Z 1Y6, Canada. [Min, James K.] Weill Cornell Med Coll, Dept Radiol, New York, NY USA. [Min, James K.] New York Presbyterian Hosp, New York, NY USA. [George, Richard T.] Johns Hopkins Univ, Dept Med, Div Cardiol, Baltimore, MD USA. RP Cury, RC (reprint author), Baptist Hosp Miami, Dept Radiol, 8900 North Kendall Dr, Miami, FL 33176 USA. EM rcury@baptisthealth.net OI Budoff, Matthew/0000-0002-9616-1946 FU Astellas; GE Healthcare; Heartflow; Abbott Vascular; ICON Medical Imaging; Toshiba; Astellas Pharma Global Development; Astellas Scientific and Medical Affairs, Inc. FX Ricardo C. Cury has received grants and research support from Astellas. Therese M. Kitt, Kathleen Feaheny, and Jamie Akin are employees of Astellas. Ron Blankstein has received grants and research support from Astellas. Matthew J. Budoff has received grants and research support from Astellas and GE Healthcare. Jonathon Leipsic has received consulting fees and honoraria from GE Healthcare and Heartflow and fees for image reading from ICON and Astellas for this study. James K. Min has research agreements with Philips Healthcare and Vital Images, has received consulting fees and honoraria from Abbott Vascular, GE Healthcare, and Heartflow, has served on medical advisory boards for Arineta, and holds equity interest in Autoplaq, MDDX, and TC3. Richard T. George has received consulting fees and honoraria from ICON Medical Imaging, has served on advisory boards for Astellas, has received grants and research support from Toshiba and GE Healthcare, educational grants from Toshiba, holds a patent for an x-ray CT apparatus and myocardial perfusion image generating system (US 7,853,309, issued December 2010), and has a pending patent for "combined multi-detector CT angiography and CT myocardial perfusion imaging for the diagnosis of coronary artery disease" (US 201110110,488, filed September 2008). Brian B. Ghoshhajra has no potential conflicts of interest to declare.; The study was supported by Astellas Pharma Global Development. Medical writing support was provided by Emily Howard and Tara N Miller, PhD, and by medical writers at Envision Scientific Solutions, and was funded by Astellas Scientific and Medical Affairs, Inc. NR 35 TC 12 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD MAR-APR PY 2015 VL 9 IS 2 BP 103 EP 112 DI 10.1016/j.jcct.2015.01.002 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CF8QP UT WOS:000352827300003 PM 25726411 ER PT J AU Atreya, CE Corcoran, RB Kopetz, S AF Atreya, Chloe E. Corcoran, Ryan B. Kopetz, Scott TI Expanded RAS: Refining the Patient Population SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID METASTATIC COLORECTAL-CANCER; KRAS WILD-TYPE; 1ST-LINE TREATMENT; ACQUIRED-RESISTANCE; PHASE-III; MUTATIONS; CETUXIMAB; CHEMOTHERAPY; PANITUMUMAB; TRIAL C1 [Atreya, Chloe E.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Corcoran, Ryan B.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Corcoran, Ryan B.] Harvard Univ, Sch Med, Boston, MA USA. [Kopetz, Scott] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Atreya, CE (reprint author), Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. EM chloe.atreya@ucsf.edu FU NCI NIH HHS [R01 CA184843, K08 CA166510, K08 CA175153, K08CA175143, P30 CA016672, R01 CA172670, R01CA172670, R01CA184843] NR 38 TC 27 Z9 27 U1 0 U2 4 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 MAR 1 PY 2015 VL 33 IS 7 BP 682 EP 685 DI 10.1200/JCO.2014.58.9325 PG 4 WC Oncology SC Oncology GA CF4MW UT WOS:000352524200006 PM 25584005 ER PT J AU McCormick, B Winter, K Hudis, C Kuerer, HM Rakovitch, E Smith, BL Sneige, N Moughan, J Shah, A Germain, I Hartford, AC Rashtian, A Walker, EM Yuen, A Strom, EA Wilcox, JL Vallow, LA Small, W Pu, AT Kerlin, K White, J AF McCormick, Beryl Winter, Kathryn Hudis, Clifford Kuerer, Henry Mark Rakovitch, Eileen Smith, Barbara L. Sneige, Nour Moughan, Jennifer Shah, Amit Germain, Isabelle Hartford, Alan C. Rashtian, Afshin Walker, Eleanor M. Yuen, Albert Strom, Eric A. Wilcox, Jeannette L. Vallow, Laura A. Small, William, Jr. Pu, Anthony T. Kerlin, Kevin White, Julia TI RTOG 9804: A Prospective Randomized Trial for Good-Risk Ductal Carcinoma In Situ Comparing Radiotherapy With Observation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BREAST-CONSERVING SURGERY; SURGICAL ADJUVANT BREAST; 20-YEAR FOLLOW-UP; LOCAL RECURRENCE; CLINICAL-TRIALS; CANCER; IRRADIATION; MASTECTOMY; LUMPECTOMY; TAMOXIFEN AB Purpose The Radiation Therapy Oncology Group 9804 study identified good-risk patients with ductal carcinoma in situ (DCIS), a breast cancer diagnosis found frequently in mammographically detected cancers, to test the benefit of radiotherapy (RT) after breast-conserving surgery compared with observation. Patients and Methods This prospective randomized trial (1998 to 2006) in women with mammographically detected low- or intermediate-grade DCIS, measuring less than 2.5 cm with margins 3 mm, compared RT with observation after surgery. The study was designed for 1,790 patients but was closed early because of lower than projected accrual. Six hundred thirty-six patients from the United States and Canada were entered; tamoxifen use (62%) was optional. Ipsilateral local failure (LF) was the primary end point; LF and contralateral failure were estimated using cumulative incidence, and overall and disease-free survival were estimated using the Kaplan-Meier method. Results Median follow-up time was 7.17 years (range, 0.01 to 11.33 years). Two LFs occurred in the RT arm, and 19 occurred in the observation arm. At 7 years, the LF rate was 0.9% (95% CI, 0.0% to 2.2%) in the RT arm versus 6.7% (95% CI, 3.2% to 9.6%) in the observation arm (hazard ratio, 0.11; 95% CI, 0.03 to 0.47; P < .001). Grade 1 to 2 acute toxicities occurred in 30% and 76% of patients in the observation and RT arms, respectively; grade 3 or 4 toxicities occurred in 4.0% and 4.2% of patients, respectively. Late RT toxicity was grade 1 in 30%, grade 2 in 4.6%, and grade 3 in 0.7% of patients. Conclusion In this good-risk subset of patients with DCIS, with a median follow-up of 7 years, the LF rate was low with observation but was decreased significantly with the addition of RT. Longer follow-up is planned because the timeline for LF in this setting seems protracted. (C) 2015 by American Society of Clinical Oncology C1 [McCormick, Beryl; Hudis, Clifford] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Winter, Kathryn; Moughan, Jennifer] Radiat Therapy Oncol Grp Stat Ctr, Philadelphia, PA USA. [Shah, Amit] York Canc Ctr, York, N Yorkshire, England. [Yuen, Albert] Reading Hosp Med Ctr, Reading, PA USA. [Kuerer, Henry Mark; Sneige, Nour; Strom, Eric A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Smith, Barbara L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hartford, Alan C.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Rashtian, Afshin] Univ So Calif, Los Angeles, CA USA. [Pu, Anthony T.] Radiol Associates Sacramento, Sacramento, CA USA. [Walker, Eleanor M.] Henry Ford Hosp, Detroit, MI 48202 USA. [Wilcox, Jeannette L.] Greenville SC Community Clin Oncol Program CCOP, Greenville, SC USA. [Vallow, Laura A.] Mayo Clin, Jacksonville, FL 32224 USA. [Small, William, Jr.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Kerlin, Kevin] Southeast Canc Control Consortium CCOP, Winston Salem, NC USA. [White, Julia] Ohio State Univ, James Canc Hosp, Columbus, OH 43210 USA. [Rakovitch, Eileen] Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. [Germain, Isabelle] LHotel Dieu Quebec, Quebec City, PQ, Canada. RP McCormick, B (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. EM mccormib@mskcc.org FU Radiation Therapy Oncology Group [U10 CA 21661]; Community Clinical Oncology Program Grant from the National Cancer Institute [U10 CA 37422] FX Supported by Radiation Therapy Oncology Group Grant No. U10 CA 21661 and Community Clinical Oncology Program Grant No. U10 CA 37422 from the National Cancer Institute. NR 26 TC 59 Z9 61 U1 2 U2 9 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 MAR 1 PY 2015 VL 33 IS 7 BP 709 EP 715 DI 10.1200/JCO.2014.57.9029 PG 7 WC Oncology SC Oncology GA CF4MW UT WOS:000352524200010 PM 25605856 ER PT J AU Bekelman, JE Mitra, N Handorf, EA Uzzo, RG Hahn, SA Polsky, D Armstrong, K AF Bekelman, Justin E. Mitra, Nandita Handorf, Elizabeth A. Uzzo, Robert G. Hahn, Stephen A. Polsky, Daniel Armstrong, Katrina TI Effectiveness of Androgen-Deprivation Therapy and Radiotherapy for Older Men With Locally Advanced Prostate Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROPENSITY SCORE; SURVIVAL; RISK; COMORBIDITY; DATABASE; DISEASE; IMPACT; DEATH; TRIAL; AGE AB Purpose We examined whether the survival advantage of androgen-deprivation therapy with radiotherapy (ADT plus RT) relative to ADT alone for men with locally advanced prostate cancer reported in two randomized trials holds in real-world clinical practice and extended the evidence to patients poorly represented in the trials. Methods We conducted nonrandomized effectiveness studies of ADT plus RT versus ADT in three groups of patients diagnosed between 1995 and 2007 and observed through 2009 in the SEER-Medicare data set: (1) the randomized clinical trial (RCT) cohort, which included men age 65 to 75 years and was most consistent with participants in the randomized trials; (2) the elderly cohort, which included men age > 75 years with locally advanced prostate cancer; and (3) the screen-detected cohort, which included men age >= 65 years with screen-detected high-risk prostate cancer. We evaluated cause-specific and all-cause mortality using propensity score, instrumental variable (IV), and sensitivity analyses. Results In the RCT cohort, ADT plus RT was associated with reduced cause-specific and all-cause mortality relative to ADT alone (cause-specific propensity score-adjusted hazard ratio [HR], 0.43; 95% CI, 0.37 to 0.49; all-cause propensity score-adjusted HR, 0.63; 95% CI, 0.59 to 0.67). Effectiveness estimates for the RCT cohort were not significantly different from those from randomized trials (P > .1). In the elderly and screen-detected cohorts, ADT plus RT was also associated with reduced cause-specific and all-cause mortality. IV analyses produced estimates similar to those from propensity score-adjusted methods. Conclusion Older men with locally advanced or screen-detected high-risk prostate cancer who receive ADT alone risk decrements in cause-specific and overall survival. (C) 2015 by American Society of Clinical Oncology C1 [Bekelman, Justin E.; Mitra, Nandita; Hahn, Stephen A.; Polsky, Daniel] Univ Penn, Philadelphia, PA 19104 USA. [Handorf, Elizabeth A.; Uzzo, Robert G.] Fox Chase Canc Ctr, Boston, MA USA. [Armstrong, Katrina] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bekelman, JE (reprint author), Univ Penn, Perelman Sch Med, Abramson Canc Ctr, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM bekelman@uphs.upenn.edu FU National Institutes of Health [RC4-CA155809]; National Cancer Institute [RC2-CA148310, K12-CA076931, K07-CA163616, UC2-CA148310]; US Public Health Service [P30-CA016520, P30-CA06927]; American Cancer Society [MRSG-121988] FX Supported by Grants No. RC4-CA155809 from the National Institutes of Health, Nos. RC2-CA148310, K12-CA076931, K07-CA163616, and UC2-CA148310 from the National Cancer Institute, Nos. P30-CA016520 and P30-CA06927 from the US Public Health Service, and No. MRSG-121988 from the American Cancer Society. NR 33 TC 19 Z9 19 U1 0 U2 3 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 MAR 1 PY 2015 VL 33 IS 7 BP 716 EP 722 DI 10.1200/JCO.2014.57.2743 PG 7 WC Oncology SC Oncology GA CF4MW UT WOS:000352524200011 PM 25559808 ER PT J AU Wagner, LI Zhao, FM Hong, FX Williams, ME Gascoyne, RD Krauss, JC Advani, RH Go, RS Habermann, TM Leach, JW O'Connor, B Schuster, SJ Cella, D Horning, SJ Kahl, BS AF Wagner, Lynne I. Zhao, Fengmin Hong, Fangxin Williams, Michael E. Gascoyne, Randy D. Krauss, John C. Advani, Ranjana H. Go, Ronald S. Habermann, Thomas M. Leach, Joseph W. O'Connor, Brian Schuster, Stephen J. Cella, David Horning, Sandra J. Kahl, Brad S. TI Anxiety and Health-Related Quality of Life Among Patients With Low-Tumor Burden Non-Hodgkin Lymphoma Randomly Assigned to Two Different Rituximab Dosing Regimens: Results From ECOG Trial E4402 (RESORT) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LONG-TERM SURVIVORS; TOP 5 LIST; FOLLICULAR LYMPHOMA; FUNCTIONAL ASSESSMENT; CLINICAL ONCOLOGY; MENTAL ADJUSTMENT; AMERICAN SOCIETY; DEPRESSION SCALE; HOSPITAL ANXIETY; CANCER-PATIENTS AB Purpose The purpose of this study was to compare illness-related anxiety among participants in the Rituximab Extended Schedule or Retreatment Trial (RESORT) randomly assigned to maintenance rituximab (MR) versus rituximab re-treatment (RR). A secondary objective was to examine whether the superiority of MR versus RR on anxiety depended on illness-related coping style. Patients and Methods Patients (N = 253) completed patient-reported outcome (PRO) measures at random assignment to MR or RR (baseline); at 3, 6, 12, 24, 36, and 48 months after random assignment; and at rituximab failure. PRO measures assessed illness-related anxiety and coping style, and secondary end points including general anxiety, worry and interference with emotional well-being, depression, and health-related quality of life (HRQoL). Patients were classified as using an active or avoidant illness-related coping style. Independent sample t tests and linear mixed-effects models were used to identify treatment arm differences on PRO end points and differences based on coping style. Results Illness-related anxiety was comparable between treatment arms at all time points (P > .05), regardless of coping style (active or avoidant). Illness-related anxiety and general anxiety significantly decreased over time on both arms. HRQoL scores were relatively stable and did not change significantly from baseline for both arms. An avoidant coping style was associated with significantly higher anxiety (18% and 13% exceeded clinical cutoff points at baseline and 6 months, respectively) and poorer HRQoL compared with an active coping style (P < .001), regardless of treatment arm assignment. Conclusion Surveillance until RR at progression was not associated with increased anxiety compared with MR, regardless of coping style. Avoidant coping was associated with higher anxiety and poorer HRQoL. (C) 2015 by American Society of Clinical Oncology C1 [Wagner, Lynne I.; Cella, David] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Zhao, Fengmin; Hong, Fangxin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Williams, Michael E.] Univ Virginia, Charlottesville, VA USA. [Krauss, John C.] Univ Michigan, Ann Arbor, MI USA. [Advani, Ranjana H.] Stanford Univ, Stanford, CA 94305 USA. [Horning, Sandra J.] Genentech Inc, South San Francisco, CA USA. [Kahl, Brad S.] Univ Wisconsin, Madison, WI USA. [Habermann, Thomas M.] Mayo Clin, Rochester, MN USA. [Leach, Joseph W.] Metro Minnesota Community Clin Oncol Program, Minneapolis, MN USA. [O'Connor, Brian] Frederick Mem Hlth Syst, Frederick, MD USA. [Schuster, Stephen J.] Univ Penn, Philadelphia, PA 19104 USA. [Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. RP Wagner, LI (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, 633 N St Clair St,19th Floor, Chicago, IL 60611 USA. EM lwagner@northwestern.edu FU National Cancer Institute, National Institutes of Health [CA21115, CA23318, CA66636, CA49957, CA21076, C47145, CA035267, C46116, C45488, C43650]; Department of Health and Human Services FX Supported in part by Public Health Service Grants No. CA21115, CA23318, CA66636, CA49957, CA21076, C47145, C43650, CA035267, C46116, CA21076, C45488, and C43650 from the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. NR 43 TC 8 Z9 8 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2015 VL 33 IS 7 BP 740 EP 748 DI 10.1200/JCO.2014.57.6801 PG 9 WC Oncology SC Oncology GA CF4MW UT WOS:000352524200014 PM 25605841 ER PT J AU Park, ER Kirchhoff, AC Perez, GK Leisenring, W Weissman, JS Donelan, K Mertens, AC Reschovsky, JD Armstrong, GT Robison, LL Franklin, M Hyland, KA Diller, LR Recklitis, CJ Kuhlthau, KA AF Park, Elyse R. Kirchhoff, Anne C. Perez, Giselle K. Leisenring, Wendy Weissman, Joel S. Donelan, Karen Mertens, Ann C. Reschovsky, James D. Armstrong, Gregory T. Robison, Leslie L. Franklin, Mariel Hyland, Kelly A. Diller, Lisa R. Recklitis, Christopher J. Kuhlthau, Karen A. TI Childhood Cancer Survivor Study Participants' Perceptions and Understanding of the Affordable Care Act SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PEDIATRIC CANCER; COVERAGE AB Purpose The Patient Protection and Affordable Care Act (ACA) established provisions intended to increase access to affordable health insurance and thus increase access to medical care and long-term surveillance for populations with pre-existing conditions. However, childhood cancer survivors' coverage priorities and familiarity with the ACA are unknown. Methods Between May 2011 and April 2012, we surveyed a randomly selected, age-stratified sample of 698 survivors and 210 siblings from the Childhood Cancer Survivor Study. Results Overall, 89.8% of survivors and 92.1% of siblings were insured. Many features of insurance coverage that survivors considered very important are addressed by the ACA, including increased availability of primary care (94.6%), no waiting period before coverage initiation (79.0%), and affordable premiums (88.1%). Survivors were more likely than siblings to deem primary care physician coverage and choice, protections from costs due to pre-existing conditions, and no start-up period as very important (P < .05 for all). Only 27.3% of survivors and 26.2% of siblings reported familiarity with the ACA (12.1% of uninsured v 29.0% of insured survivors; odds ratio, 2.86; 95% CI, 1.28 to 6.36). Only 21.3% of survivors and 18.9% of siblings believed the ACA would make it more likely that they would get quality coverage. Survivors' and siblings' concerns about the ACA included increased costs, decreased access to and quality of care, and negative impact on employers and employees. Conclusion Although survivors' coverage preferences match many ACA provisions, survivors, particularly uninsured survivors, were not familiar with the ACA. Education and assistance, perhaps through cancer survivor navigation, are critically needed to ensure that survivors access coverage and benefits. (C) 2015 by American Society of Clinical Oncology C1 [Park, Elyse R.; Perez, Giselle K.; Donelan, Karen; Franklin, Mariel; Kuhlthau, Karen A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Weissman, Joel S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Diller, Lisa R.; Recklitis, Christopher J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kirchhoff, Anne C.] Huntsman Canc Inst, Salt Lake City, UT USA. [Leisenring, Wendy] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Mertens, Ann C.] Emory Univ, Sch Med, Atlanta, GA USA. [Reschovsky, James D.] Math Policy Res, Washington, DC USA. [Armstrong, Gregory T.; Robison, Leslie L.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. RP Park, ER (reprint author), Massachusetts Gen Hosp, 50 Staniford St,Ste 901, Boston, MA 02114 USA. EM epark@partners.org FU Livestrong Foundation; National Cancer Institute [U24 CA55727]; Cancer Center Support (CORE) Grant [CA21765]; American Lebanese-Syrian Associated Charities FX Supported by the Livestrong Foundation and National Cancer Institute (Grant No. U24 CA55727, G.T. Armstrong, principal investigator). Support to St Jude Children's Research Hospital also provided by Cancer Center Support (CORE) Grant No. CA21765 (R. Gilbertson, principal investigator) and the American Lebanese-Syrian Associated Charities. NR 14 TC 7 Z9 7 U1 0 U2 2 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 MAR 1 PY 2015 VL 33 IS 7 BP 764 EP 772 DI 10.1200/JCO.2014.58.0993 PG 9 WC Oncology SC Oncology GA CF4MW UT WOS:000352524200017 PM 25646189 ER PT J AU Mitsiades, CS AF Mitsiades, Constantine S. TI Therapeutic Landscape of Carfilzomib and Other Modulators of the Ubiquitin-Proteasome Pathway SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID REFRACTORY MULTIPLE-MYELOMA; LOW-DOSE DEXAMETHASONE; PROTEIN-QUALITY CONTROL; MANTLE CELL LYMPHOMA; PHASE-I TRIAL; WALDENSTROMS MACROGLOBULINEMIA; HEMATOLOGIC MALIGNANCIES; IRREVERSIBLE INHIBITOR; COMBINATION THERAPY; PRECLINICAL MODELS C1 [Mitsiades, Constantine S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mitsiades, Constantine S.] Harvard Univ, Sch Med, Boston, MA USA. RP Mitsiades, CS (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. FU National Institutes of Health [R01 CA127435, R01 CA179483, P01 CA155258]; Shawna Ashlee Corman Investigatorship in Multiple Myeloma Research; de Gunzburg Myeloma Research Fund; Cobb Family Myeloma Research Fund; Chambers Family Advanced Myeloma Research Fund; Leukemia and Lymphoma Society Translational Research Program; Elsa U. Pardee Foundation; Multiple Myeloma Research Foundation; Quest for Cure Program FX Supported by Grants No. R01 CA127435, R01 CA179483, and P01 CA155258 (C.S.M.) from the National Institutes of Health, by the Shawna Ashlee Corman Investigatorship in Multiple Myeloma Research, the de Gunzburg Myeloma Research Fund, the Cobb Family Myeloma Research Fund, the Chambers Family Advanced Myeloma Research Fund, the Leukemia and Lymphoma Society Translational Research Program and Quest for Cure Program, the Elsa U. Pardee Foundation, and the Multiple Myeloma Research Foundation. NR 76 TC 3 Z9 3 U1 0 U2 2 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 MAR 1 PY 2015 VL 33 IS 7 BP 782 EP 785 DI 10.1200/JCO.2014.55.5748 PG 4 WC Oncology SC Oncology GA CF4MW UT WOS:000352524200019 PM 25605842 ER PT J AU Masters, GA Krilov, L Bailey, HH Brose, MS Burstein, H Diller, LR Dizon, DS Fine, HA Kalemkerian, GP Moasser, M Neuss, MN O'Day, SJ Odenike, O Ryan, CJ Schilsky, RL Schwartz, GK Venook, AP Wong, SL Patel, JD AF Masters, Gregory A. Krilov, Lada Bailey, Howard H. Brose, Marcia S. Burstein, Harold Diller, Lisa R. Dizon, Don S. Fine, Howard A. Kalemkerian, Gregory P. Moasser, Mark Neuss, Michael N. O'Day, Steven J. Odenike, Olatoyosi Ryan, Charles J. Schilsky, Richard L. Schwartz, Gary K. Venook, Alan P. Wong, Sandra L. Patel, Jyoti D. TI Clinical Cancer Advances 2015: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SMALL-CELL CARCINOMA; ACTIVATING ACVR1 MUTATIONS; EARLY PALLIATIVE CARE; SERVICES TASK-FORCE; LUNG-CANCER; HYPERCALCEMIC TYPE; SMARCA4 MUTATIONS; TRIAL; OVARY; RISK C1 [Masters, Gregory A.] Helen F Graham Canc Ctr, Newark, DE USA. [Krilov, Lada; Schilsky, Richard L.] Amer Soc Clin Oncol, Alexandria, VA 22314 USA. [Bailey, Howard H.] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. [Brose, Marcia S.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Burstein, Harold; Diller, Lisa R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dizon, Don S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fine, Howard A.] NYU, Langone Med Ctr, New York, NY USA. [Schwartz, Gary K.] Columbia Univ, Med Ctr, New York, NY USA. [Kalemkerian, Gregory P.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Wong, Sandra L.] Univ Michigan, Ann Arbor, MI 48109 USA. [Moasser, Mark] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Ryan, Charles J.; Venook, Alan P.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [O'Day, Steven J.] Beverly Hills Hlth Ctr, Beverly Hills, CA USA. [Neuss, Michael N.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Odenike, Olatoyosi] Univ Chicago, Chicago, IL 60637 USA. [Patel, Jyoti D.] Northwestern Univ, Chicago, IL 60611 USA. RP Krilov, L (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA. EM lada.krilov@asco.org FU Eli Lilly/ImClone; Bayer HealthCare Pharmaceuticals (Inst); Eisai (Inst); Novartis (Inst); Roche/Genentech (Inst); Exelixis (Inst); Merck (Inst); OncoMed (Inst); GlaxoSmithKline (Inst); Millennium Pharmaceuticals (Inst); Pfizer (Inst); Merck, Bristol-Myers Squibb; Novartis; Amgen; Spectrum Pharmaceuticals (Inst); Celgene (Inst); Incyte (Inst); Astex Therapeutics (Inst); S*Bio (Inst); sanofi-aventis (Inst); Suneisis (Inst); NS-Pharma (Inst); MEI Pharma (Inst); sanofi-aventis; Bayer Pharmaceuticals (Inst); Onyx Pharmaceuticals (Inst); Genentech/Roche (Inst); Bristol-Myers Squibb (Inst) FX Research Funding: Eli Lilly/ImClone; Research Funding: Bayer HealthCare Pharmaceuticals (Inst), Eisai (Inst), Novartis (Inst), Roche/Genentech (Inst), Exelixis (Inst); Research Funding: Merck (Inst), OncoMed (Inst), Novartis (Inst), GlaxoSmithKline (Inst), Millennium Pharmaceuticals (Inst), Pfizer (Inst); Research Funding: Merck, Bristol-Myers Squibb, Novartis, Amgen; Research Funding: Eisai (Inst), Spectrum Pharmaceuticals (Inst), Celgene (Inst), Incyte (Inst), Astex Therapeutics (Inst), S*Bio (Inst), sanofi-aventis (Inst), Suneisis (Inst), NS-Pharma (Inst), MEI Pharma (Inst); Research Funding: sanofi-aventis; Research Funding: Bayer Pharmaceuticals (Inst), Onyx Pharmaceuticals (Inst), Genentech/Roche (Inst), Bristol-Myers Squibb (Inst), GlaxoSmithKline (Inst) NR 46 TC 34 Z9 35 U1 1 U2 10 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 MAR 1 PY 2015 VL 33 IS 7 BP 786 EP 809 DI 10.1200/JCO.2014.59.9746 PG 24 WC Oncology SC Oncology GA CF4MW UT WOS:000352524200020 PM 25605863 ER PT J AU Sarris, J Logan, AC Akbaraly, TN Amminger, GP Balanza-Martinez, V Freeman, MP Hibbeln, J Matsuoka, Y Mischoulon, D Mizoue, T Nanri, A Nishi, D Ramsey, D Rucklidge, JJ Sanchez-Villegas, A Scholey, A Su, KP Jacka, FN AF Sarris, Jerome Logan, Alan C. Akbaraly, Tasnime N. Amminger, G. Paul Balanza-Martinez, Vicent Freeman, Marlene P. Hibbeln, Joseph Matsuoka, Yutaka Mischoulon, David Mizoue, Tetsuya Nanri, Akiko Nishi, Daisuke Ramsey, Drew Rucklidge, Julia J. Sanchez-Villegas, Almudena Scholey, Andrew Su, Kuan-Pin Jacka, Felice N. CA Int Soc Nutr Psychiat Res TI Nutritional medicine as mainstream in psychiatry SO LANCET PSYCHIATRY LA English DT Editorial Material ID S-ADENOSYL METHIONINE; DUTCH-HUNGER-WINTER; DIETARY PATTERNS; MENTAL-HEALTH; PRENATAL EXPOSURE; MAJOR DEPRESSION; ADULTS; EFFICACY; TRIAL; METAANALYSIS AB Psychiatry is at an important juncture, with the current pharmacologically focused model having achieved modest benefits in addressing the burden of poor mental health worldwide. Although the determinants of mental health are complex, the emerging and compelling evidence for nutrition as a crucial factor in the high prevalence and incidence of mental disorders suggests that diet is as important to psychiatry as it is to cardiology, endocrinology, and gastroenterology. Evidence is steadily growing for the relation between dietary quality (and potential nutritional deficiencies) and mental health, and for the select use of nutrient-based supplements to address deficiencies, or as monotherapies or augmentation therapies. We present a viewpoint from an international collaboration of academics (members of the International Society for Nutritional Psychiatry Research), in which we provide a context and overview of the current evidence in this emerging field of research, and discuss the future direction. We advocate recognition of diet and nutrition as central determinants of both physical and mental health. C1 [Sarris, Jerome] Univ Melbourne, Melbourne Clin, Melbourne, Vic, Australia. [Jacka, Felice N.] Univ Melbourne, Royal Melbourne Hosp, Dept Psychiat, Melbourne, Vic 3050, Australia. [Sarris, Jerome; Scholey, Andrew] Swinburne Univ Technol, Ctr Human Psychopharmacol, Hawthorn, Vic 3122, Australia. [Logan, Alan C.] CAMNR, Calabasas, CA USA. [Akbaraly, Tasnime N.] Univ Montpellier, INSERM, U710, F-34059 Montpellier, France. [Akbaraly, Tasnime N.] UCL, Dept Epidemiol & Publ Hlth, London, England. [Amminger, G. Paul] Orygen Youth Hlth Res Ctr, Parkville, Vic, Australia. [Balanza-Martinez, Vicent] La Fe Univ, Teaching Unit Psychiat & Psychol Med, Valencia, Spain. [Balanza-Martinez, Vicent] Univ Valencia, Polytech Hosp, Sch Med, Ctr Invest Biomed Red Salud Mental CIBERSAM, Valencia, Spain. [Freeman, Marlene P.] Massachusetts Gen Hosp, Perinatal & Reprod Psychiat, Boston, MA 02114 USA. [Mischoulon, David] Massachusetts Gen Hosp, Depress & Clincal Res Program, Boston, MA 02114 USA. [Hibbeln, Joseph] NIAAA, NIH, Bethesda, MD USA. [Matsuoka, Yutaka] Natl Ctr Neurol & Psychiat, Dept Clin Epidemiol, Translat Med Ctr, Kodaira, Tokyo, Japan. [Nishi, Daisuke] Natl Ctr Neurol & Psychiat, Natl Inst Mental Hlth, Dept Mental Hlth Policy & Evaluat, Kodaira, Tokyo, Japan. [Mizoue, Tetsuya; Nanri, Akiko] Natl Ctr Global Hlth & Med, Dept Epidemiol & Prevent, Ctr Clin Sci, Shijuku Ku, Tokyo, Japan. [Ramsey, Drew] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Rucklidge, Julia J.] Univ Canterbury, Dept Psychol, Christchurch 1, New Zealand. [Sanchez-Villegas, Almudena] Univ Las Palmas Gran Canaria, Dept Clin Sci, Las Palmas Gran Canaria, Spain. [Su, Kuan-Pin] China Med Univ, Dept Psychiat, Taichung, Taiwan. [Su, Kuan-Pin] China Med Univ, Mind Body Interface Lab MBI Lab, China Med Univ Hosp, Taichung, Taiwan. [Su, Kuan-Pin] China Med Univ, Grad Inst Neural & Cognit Sci, Taichung, Taiwan. [Jacka, Felice N.] Deakin Univ, Sch Med, IMPACT Strateg Res Ctr, Geelong, Vic 3217, Australia. [Jacka, Felice N.] Murdoch Childrens Res Ctr, Parkville, Vic, Australia. [Jacka, Felice N.] Hosp Rd Prince Wales Hosp, Black Dog Inst, Randwick, NSW, Australia. RP Sarris, J (reprint author), Melbourne Clin, 2 Salisbury St, Melbourne, Vic 3121, Australia. EM jsarris@unimelb.edu.au FU Integria Health; Blackmores; Bioceuticals; Taki Mai; Pepsico; HealthEd; Soho-Flordis; Pfizer; Elsevier; Society for Medicinal Plant and Natural Product Research; CR Roper Fellowship; National Health and Medical Research Council (NHMRC); Genuine Health (Toronto, Canada); Angelini; AstraZeneca; Bristol-Myers-Squibb; Janssen; Juste; Lilly; Lundbeck; Otsuka; Spanish Ministry of Science and Innovation; Fundacion Alicia Koplowitz; Takeda; Genentech; Johnson Johnson; JDS Therapeutics; Japan Science and Technology Agency; National Center of Neurology and Psychiatry (Japan); Ministry of Health, Labour, and Welfare of Japan; Mochida Pharmaceutical Co; Takeda Pharmaceutical Company; Suntory Wellness; Eli Lilly Japan KK; Otsuka Pharmaceutical Co; DHA & EPA Association; Bowman Family Foundation; FisherWallace; Nordic Naturals; Methylation Sciences; PharmoRx Therapeutics; Japan Society for the Promotion of Science; National Center for Global Health and Medicine (Japan); National Cancer Center (Japan); Industrial Health Foundation; Uehara Memorial Foundation; Otsuka Pharmaceutical Co.; Foundation for Total Health Promotion; Qol Co; NTT DoCoMo; Emotional Quotient Academy; Biotechnology and Biological Sciences Research Council (UK); Australian Research Council; NHMRC; British Psychological Society; Australian Wine Research Institute; Abbott Nutrition; Arla Foods; Bayer Healthcare; Cognis; Cyvex; GlaxoSmithKline Nutrition; Masterfoods; Martek; Naturex; Nestle; Neurobrands; Sanofi; Verdure Sciences; Wrigley; Barilla; Danone; Flordis; GlaxoSmithKline Healthcare; Kraft; Novartis; Unilever; National Science Council; National Health Research Institute; China Medical University in Taiwan; Royal Society (UK); National Centre for Research and Development (Poland); Brain and Behaviour Research Institute (USA); Australian Rotary Health; Geelong Medical Research Foundation; Ian Potter Foundation; Eli Lilly; Meat and Livestock Board Australia; University of Melbourne; Sanofi -Synthelabo; Janssen Cilag; Servier; Health Ed; Network Nutrition; Angelini Farmaceutica FX JS has received honoraria, research support, royalties, consultancy, or travel grant funding from Integria Health, Blackmores, Bioceuticals, Taki Mai, Pepsico, HealthEd, Soho-Flordis, Pfizer, Elsevier,the Society for Medicinal Plant and Natural Product Research, CR Roper Fellowship, and the National Health and Medical Research Council (NHMRC). ACL has received consulting fees from Genuine Health (Toronto, Canada). VB-M has received grants, and served as consultant, adviser, or continuing medical education (CME) speaker during the past 3 years for the following entities: Angelini, AstraZeneca, Bristol-Myers-Squibb, Janssen, Juste, Lilly, Lundbeck, Otsuka, the Spanish Ministry of Science and Innovation, and Fundacion Alicia Koplowitz. MPF has received funding for advisory board positions, or consulting, from: Takeda, Otsuka, Lundbeck, Genentech, Johnson & Johnson, and JDS Therapeutics; pending research support from Takeda; and for medical editing for DSM Nutritionals and GOED Omega-3. YM has received research support from the Japan Science and Technology Agency, National Center of Neurology and Psychiatry (Japan), the Ministry of Health, Labour, and Welfare of Japan, and has been a paid speaker for Mochida Pharmaceutical Co, Takeda Pharmaceutical Company, Suntory Wellness, Eli Lilly Japan KK, Otsuka Pharmaceutical Co, and DHA & EPA Association. DM has received research support from the Bowman Family Foundation, FisherWallace, Nordic Naturals, Methylation Sciences, and PharmoRx Therapeutics. He has received honoraria for consulting, speaking, and writing from Pamlab, and the Massachusetts General Hospital Psychiatry Academy. He has received royalties from Lippincott Williams & Wilkins for the published book Natural medications for psychiatric disorders: considering the alternatives. TM has received research grants from the Japan Society for the Promotion of Science, the National Center for Global Health and Medicine (Japan), the National Cancer Center (Japan), the Ministry of Health, Labour, and Welfare of Japan, the Industrial Health Foundation, the Uehara Memorial Foundation, and Otsuka Pharmaceutical Co. DN has received research support from the Japan Society for the Promotion of Science and the Foundation for Total Health Promotion, and lecture fees from Qol Co, DHA & EPA Association, NTT DoCoMo, and Emotional Quotient Academy. AS has received funding from the Biotechnology and Biological Sciences Research Council (UK), The Australian Research Council, the NHMRC, the British Psychological Society, the Australian Wine Research Institute, Abbott Nutrition, Arla Foods, Bayer Healthcare, Cognis, Cyvex, GlaxoSmithKline Nutrition, Masterfoods, Martek, Naturex, Nestle, Neurobrands, Sanofi, Verdure Sciences, and Wrigley, and received speaker fees from Abbott Nutrition, Barilla, Bayer Healthcare, Danone, Flordis, GlaxoSmithKline Healthcare, Kraft, Masterfoods, Martek, Novartis, Unilever, and Wrigley. K-PS has received research grants from the National Science Council, National Health Research Institute, and China Medical University in Taiwan, and joint research grants from the Royal Society (UK) and National Centre for Research and Development (Poland).; FNJ has received grants and research support from the Brain and Behaviour Research Institute (USA), the NHMRC, Australian Rotary Health, the Geelong Medical Research Foundation, the Ian Potter Foundation, Eli Lilly, the Meat and Livestock Board Australia, and The University of Melbourne, and has been a paid speaker for Sanofi -Synthelabo, Janssen Cilag, Servier, Pfizer, Health Ed, Network Nutrition, Angelini Farmaceutica, and Eli Lilly. NR 31 TC 38 Z9 38 U1 8 U2 51 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2215-0374 J9 LANCET PSYCHIAT JI Lancet Psychiatry PD MAR PY 2015 VL 2 IS 3 BP 271 EP 274 DI 10.1016/S2215-0366(14)00051-0 PG 4 WC Psychiatry SC Psychiatry GA CF6ZX UT WOS:000352706800025 PM 26359904 ER PT J AU Saddawi-Konefka, D Alston, TA AF Saddawi-Konefka, D. Alston, T. A. TI An electrocardiographic monitor for reducing hemodynamic suspense during suspension laryngoscopy SO MINERVA ANESTESIOLOGICA LA English DT Editorial Material ID HEART-RATE-VARIABILITY C1 [Saddawi-Konefka, D.; Alston, T. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Alston, TA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM talston@mgh.harvard.edu NR 20 TC 1 Z9 1 U1 0 U2 0 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0375-9393 EI 1827-1596 J9 MINERVA ANESTESIOL JI Minerva Anestesiol. PD MAR PY 2015 VL 81 IS 3 BP 255 EP 257 PG 3 WC Anesthesiology; Critical Care Medicine SC Anesthesiology; General & Internal Medicine GA CF7OZ UT WOS:000352747500003 PM 25220558 ER PT J AU Patsoukis, N Bardhan, K Chatterjee, P Sari, D Liu, BL Bell, LN Karoly, ED Freeman, GJ Petkova, V Seth, P Li, LQ Boussiotis, VA AF Patsoukis, Nikolaos Bardhan, Kankana Chatterjee, Pranam Sari, Duygu Liu, Bianling Bell, Lauren N. Karoly, Edward D. Freeman, Gordon J. Petkova, Victoria Seth, Pankaj Li, Lequn Boussiotis, Vassiliki A. TI PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation SO NATURE COMMUNICATIONS LA English DT Article ID CHRONIC VIRAL-INFECTION; RESPIRATORY CAPACITY; DISEASE PROGRESSION; SIGNALING PATHWAY; LIPID-METABOLISM; TUMOR-GROWTH; ACTIVATION; EXPRESSION; MEMORY; CTLA-4 AB During activation, T cells undergo metabolic reprogramming, which imprints distinct functional fates. We determined that on PD-1 ligation, activated T cells are unable to engage in glycolysis or amino acid metabolism but have an increased rate of fatty acid beta-oxidation (FAO). PD-1 promotes FAO of endogenous lipids by increasing expression of CPT1A, and inducing lipolysis as indicated by elevation of the lipase ATGL, the lipolysis marker glycerol and release of fatty acids. Conversely, CTLA-4 inhibits glycolysis without augmenting FAO, suggesting that CTLA-4 sustains the metabolic profile of non-activated cells. Because T cells utilize glycolysis during differentiation to effectors, our findings reveal a metabolic mechanism responsible for PD-1-mediated blockade of T-effector cell differentiation. The enhancement of FAO provides a mechanistic explanation for the longevity of T cells receiving PD-1 signals in patients with chronic infections and cancer, and for their capacity to be reinvigorated by PD-1 blockade. C1 [Patsoukis, Nikolaos; Bardhan, Kankana; Chatterjee, Pranam; Sari, Duygu; Liu, Bianling; Petkova, Victoria; Li, Lequn; Boussiotis, Vassiliki A.] Harvard Univ, Sch Med, Div Hematol Oncol, Boston, MA 02215 USA. [Patsoukis, Nikolaos; Bardhan, Kankana; Chatterjee, Pranam; Sari, Duygu; Liu, Bianling; Petkova, Victoria; Seth, Pankaj; Li, Lequn; Boussiotis, Vassiliki A.] Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Patsoukis, Nikolaos; Bardhan, Kankana; Chatterjee, Pranam; Sari, Duygu; Liu, Bianling; Petkova, Victoria; Seth, Pankaj; Li, Lequn; Boussiotis, Vassiliki A.] Harvard Univ, Sch Med, Beth Israel Deaconess Canc Ctr, Boston, MA 02215 USA. [Bell, Lauren N.; Karoly, Edward D.] Metabolon Inc, Durham, NC 27713 USA. [Freeman, Gordon J.] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02284 USA. [Seth, Pankaj] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Interdisciplinary Med & Biotechnol, Boston, MA 02215 USA. RP Boussiotis, VA (reprint author), Harvard Univ, Sch Med, Div Hematol Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM vboussio@bidmc.harvard.edu FU NIH [CA183605, AI098129, AI056299, HHSN2722018C] FX This work was supported by NIH grants CA183605 and AI098129 (to V.A.B.) and AI056299 and HHSN2722018C (to G.J.F.). NR 60 TC 55 Z9 56 U1 9 U2 28 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 MAR PY 2015 VL 6 AR 6692 DI 10.1038/ncomms7692 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG1OR UT WOS:000353043100001 PM 25809635 ER PT J AU Reardon, DA Nabors, LB Mason, WP Perry, JR Shapiro, W Kavan, P Mathieu, D Phuphanich, S Cseh, A Fu, YL Cong, J Wind, S Eisenstat, DD AF Reardon, David A. Nabors, Louis B. Mason, Warren P. Perry, James R. Shapiro, William Kavan, Petr Mathieu, David Phuphanich, Surasak Cseh, Agnieszka Fu, Yali Cong, Julie Wind, Sven Eisenstat, David D. CA BI 1200 36 Trial Grp Canadian Brain Tumour Consortium TI Phase I/randomized phase II study of afatinib, an irreversible ErbB family blocker, with or without protracted temozolomide in adults with recurrent glioblastoma SO NEURO-ONCOLOGY LA English DT Article DE afatinib; EGFRvIII; ErbB family; glioblastoma; temozolomide ID NEWLY-DIAGNOSED GLIOBLASTOMA; GROWTH-FACTOR-RECEPTOR; EGFR KINASE INHIBITORS; NEURO-ONCOLOGIA GICNO; HIGH-GRADE GLIOMAS; CELL LUNG-CANCER; OPEN-LABEL; RADIATION-THERAPY; MALIGNANT GLIOMA; RANDOMIZED-TRIAL AB Background. This phase I/II trial evaluated the maximum tolerated dose (MTD) and pharmacokinetics of afatinib plus temozolomide as well as the efficacy and safety of afatinib as monotherapy (A) or with temozolomide (AT) vs temozolomide monotherapy (T) in patients with recurrent glioblastoma (GBM). Methods. Phase I followed a traditional 3 + 3 dose-escalation design to determine MTD. Treatment cohorts were: afatinib 20, 40, and 50 mg/day (plus temozolomide 75 mg/m(2)/day for 21 days per 28-day cycle). In phase II, participants were randomized (stratified by age and KPS) to receive A, T or AT; A was dosed at 40 mg/day and T at 75 mg/m(2) for 21 of 28 days. Primary endpoint was progression-free survival rate at 6 months (PFS-6). Participants were treated until intolerable adverse events (AEs) or disease progression. Results. Recommended phase II dose was 40 mg/day (A) + T based on safety data from phase I (n = 32). Most frequent AEs in phase II (n = 119) were diarrhea (71% [A], 82% [AT]) and rash (71% [A] and 69% [AT]). Afatinib and temozolomide pharmacokinetics were unaffected by coadministration. Independently assessed PFS-6 rate was 3% (A), 10% (AT), and 23% (T). Median PFS was longer in afatinib-treated participants with epidermal growth factor receptor (EFGR) vIII-positive tumors versus EGFRvIII-negative tumors. Best overall response included partial response in 1 (A), 2 (AT), and 4 (T) participants and stable disease in 14 (A), 14 (AT), and 21 (T) participants. Conclusions. Afatinib has a manageable safety profile but limited single-agent activity in unselected recurrent GBM patients. C1 [Reardon, David A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nabors, Louis B.] Univ Alabama Birmingham, Birmingham, AL USA. [Mason, Warren P.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Perry, James R.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Odette Canc Ctr, Toronto, ON, Canada. [Shapiro, William] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Kavan, Petr] McGill Univ, Dept Med Oncol, Montreal, PQ, Canada. [Mathieu, David] Ctr Hosp Univ Sherbrooke, Sherbrooke, PQ, Canada. [Phuphanich, Surasak; Cseh, Agnieszka] Cedars Sinai Med Ctr, Johnnie Cochran Brain Tumor Ctr, Los Angeles, CA 90048 USA. [Cseh, Agnieszka] Boehringer Ingelheim RCV GmbH & Co KG, A-1120 Vienna, Austria. [Fu, Yali; Cong, Julie] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. [Wind, Sven] Boehringer Ingelheim Pharma GmbH & Co KG, D-88400 Biberach, Germany. [Eisenstat, David D.] CancerCare Manitoba, Winnipeg, MB, Canada. RP Reardon, DA (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 450 Brookline Ave,SW G460F, Boston, MA 02115 USA. EM david_reardon@dfci.harvard.edu; eisensta@ualberta.ca FU Boehringer Ingelheim FX This study was supported by Boehringer Ingelheim. The authors were fully responsible for all content and editorial decisions, were involved at all stages of manuscript development, and have approved the final version. Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Anusha Bolonna, of Ogilvy Healthworld, during the preparation of this article. NR 45 TC 9 Z9 9 U1 0 U2 4 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 MAR PY 2015 VL 17 IS 3 BP 430 EP 439 DI 10.1093/neuonc/nou160 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CF3WM UT WOS:000352479700015 PM 25140039 ER PT J AU Luke, JJ Triozzi, PL McKenna, KC Van Meir, EG Gershenwald, JE Bastian, BC Gutkind, JS Bowcock, AM Streicher, HZ Patel, PM Sato, T Sossman, JA Sznol, M Welch, J Thurin, M Selig, S Flaherty, KT Carvajal, RD AF Luke, Jason J. Triozzi, Pierre L. McKenna, Kyle C. Van Meir, Erwin G. Gershenwald, Jeffrey E. Bastian, Boris C. Gutkind, J. Silvio Bowcock, Anne M. Streicher, Howard Z. Patel, Poulam M. Sato, Takami Sossman, Jeffery A. Sznol, Mario Welch, Jack Thurin, Magdalena Selig, Sara Flaherty, Keith T. Carvajal, Richard D. TI Biology of advanced uveal melanoma and next steps for clinical therapeutics SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Review DE Ocular; Uveal; Melanoma; MEK; GNAQ; GNA11; metastasis; cancer ID INDUCIBLE FACTOR PATHWAY; PROTEIN-KINASE-C; PHASE-II TRIAL; GROWTH-FACTOR RECEPTOR; IMMUNE PRIVILEGE; OCULAR MELANOMA; METASTATIC MELANOMA; ANTERIOR-CHAMBER; TUMOR-CELLS; LYMPHOCYTIC INFILTRATION AB Uveal melanoma is the most common intraocular malignancy although it is a rare subset of all melanomas. Uveal melanoma has distinct biology relative to cutaneous melanoma, with widely divergent patient outcomes. Patients diagnosed with a primary uveal melanoma can be stratified for risk of metastasis by cytogenetics or gene expression profiling, with approximately half of patients developing metastatic disease, predominately hepatic in location, over a 15-yr period. Historically, no systemic therapy has been associated with a clear clinical benefit for patients with advanced disease, and median survival remains poor. Here, as a joint effort between the Melanoma Research Foundation's ocular melanoma initiative, CURE OM and the National Cancer Institute, the current understanding of the molecular and immunobiology of uveal melanoma is reviewed, and on-going laboratory research into the disease is highlighted. Finally, recent investigations relevant to clinical management via targeted and immunotherpies are reviewed, and next steps in the development of clinical therapeutics are discussed. C1 [Luke, Jason J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Triozzi, Pierre L.] Wake Forest Univ, Ctr Canc, Winston Salem, NC 27109 USA. [McKenna, Kyle C.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Van Meir, Erwin G.] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA. [Gershenwald, Jeffrey E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Bastian, Boris C.] Univ Calif San Francisco, Helen Diller Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. [Bowcock, Anne M.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Streicher, Howard Z.; Welch, Jack; Thurin, Magdalena] NCI, Bethesda, MD 20892 USA. [Patel, Poulam M.] Univ Nottingham, Nottingham NG7 2RD, England. [Sato, Takami] Thomas Jefferson Univ, Vanderbilt Ingram Canc Ctr, Ctr Canc, Philadelphia, PA 19107 USA. [Sossman, Jeffery A.] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37235 USA. [Sznol, Mario] Yale Univ, Yale Canc Ctr, New Haven, CT USA. [Selig, Sara] Brigham & Womans Hosp, Washington, DC USA. [Selig, Sara] Melanoma Res Fdn, CURE OM, Washington, DC USA. [Flaherty, Keith T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. [Carvajal, Richard D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Luke, JJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Jason_Luke@dfci.harvard.edu OI Bowcock, Anne/0000-0001-8691-9090 FU NIH [R01 CA16187001, R01 CA142873, CA116804, CA176001, CA180805]; Samuel Waxman Cancer Research Foundation FX We thank Elisha Roberson for helpful comments in review of the manuscript. Anne Bowcock acknowledges funding via NIH R01 CA16187001. Boris Bastian acknowledges funding via NIH R01 CA142873. Erwin G. Van Meir acknowledges funding NIH CA116804, CA176001, and CA180805 and the Samuel Waxman Cancer Research Foundation. NR 118 TC 16 Z9 16 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-1471 EI 1755-148X J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD MAR PY 2015 VL 28 IS 2 BP 135 EP 147 DI 10.1111/pcmr.12304 PG 13 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA CF8OJ UT WOS:000352821100007 PM 25113308 ER PT J AU Webster, MR Xu, M Kinzler, KA Kaur, A Appleton, J O'Connell, MP Marchbank, K Valiga, A Dang, VM Perego, M Zhang, G Slipicevic, A Keeney, F Lehrmann, E Wood, W Becker, KG Kossenkov, AV Frederick, DT Flaherty, KT Xu, XW Herlyn, M Murphy, ME Weeraratna, AT AF Webster, Marie R. Xu, Mai Kinzler, Kathryn A. Kaur, Amanpreet Appleton, Jessica O'Connell, Michael P. Marchbank, Katie Valiga, Alexander Dang, Vanessa M. Perego, Michela Zhang, Gao Slipicevic, Ana Keeney, Frederick Lehrmann, Elin Wood, William, III Becker, Kevin G. Kossenkov, Andrew V. Frederick, Dennie T. Flaherty, Keith T. Xu, Xiaowei Herlyn, Meenhard Murphy, Maureen E. Weeraratna, Ashani T. TI Wnt5A promotes an adaptive, senescent-like stress response, while continuing to drive invasion in melanoma cells SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Article DE Wnt5A; BRAF; senescence; metastasis; therapy resistance ID CANCER-THERAPY; CELLULAR SENESCENCE; INHIBITION; VEMURAFENIB; RESISTANCE; PHOSPHORYLATION; BRAF(V600E); SUPPRESSION; EXPRESSION; PHENOTYPE AB We have previously shown that Wnt5A drives invasion in melanoma. We have also shown that Wnt5A promotes resistance to therapy designed to target the BRAF(V600E) mutation in melanoma. Here, we show that melanomas characterized by high levels of Wnt5A respond to therapeutic stress by increasing p21 and expressing classical markers of senescence, including positivity for senescence-associated beta-galactosidase (SA-beta-gal), senescence-associated heterochromatic foci (SAHF), H3K9Me chromatin marks, and PML bodies. We find that despite this, these cells retain their ability to migrate and invade. Further, despite the expression of classic markers of senescence such as SA-beta-gal and SAHF, these Wnt5A-high cells are able to colonize the lungs in in vivo tail vein colony-forming assays. This clearly underscores the fact that these markers do not indicate true senescence in these cells, but instead an adaptive stress response that allows the cells to evade therapy and invade. Notably, silencing Wnt5A reduces expression of these markers and decreases invasiveness. The combined data point to Wnt5A as a master regulator of an adaptive stress response in melanoma, which may contribute to therapy resistance. C1 [Webster, Marie R.; Kaur, Amanpreet; Appleton, Jessica; O'Connell, Michael P.; Marchbank, Katie; Valiga, Alexander; Dang, Vanessa M.; Perego, Michela; Zhang, Gao; Slipicevic, Ana; Keeney, Frederick; Kossenkov, Andrew V.; Herlyn, Meenhard; Murphy, Maureen E.; Weeraratna, Ashani T.] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. [Xu, Mai; Kinzler, Kathryn A.; Lehrmann, Elin; Wood, William, III; Becker, Kevin G.] NIA, NIH, Baltimore, MD 21224 USA. [Frederick, Dennie T.; Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Xu, Xiaowei] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Weeraratna, AT (reprint author), Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA. EM aweeraratna@wistar.org RI Zhang, Gao/D-3471-2017 FU National Institute on Aging, Baltimore, MD; PA Department of Health (CURE); CCSG [P30 CA010815]; [P01 CA 114046-06]; [T32 CA 9171-36]; [RO1 CA174746-01] FX We thank Drs Chi V. Dang (Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA), Kenneth Kinzler (Sidney Kimmel Cancer Center, Johns Hopkins University), Mina Bissell (Lawrence Berkeley Laboratories, CA, USA), Daniel Peeper (Netherlands Cancer Institute), Andrew Aplin (Thomas Jefferson University, PA, USA), and Rugang Zhang, Dmitry Gabrilovich and Dario Altieri (The Wistar Institute) for critical reading of the manuscript. We thank Dr. Jessie Villanueva (The Wistar Institute) for the use of the WM983B-resistant cells. We thank Dr. Kate Nathanson for assistance with sequencing of the cell lines. We also thank Dr. Qin Liu for assistance with statistics. This work was supported in part by funds from the Intramural Program of the National Institute on Aging, Baltimore, MD, The PA Department of Health (CURE funding) to ATW, MPO, MRW and P01 CA 114046-06 (MH, ATW, GZ, KM, MEM), T32 CA 9171-36 (MRW) and RO1 CA174746-01 (ATW, AK, QL). Core facilities at the Wistar are supported by the CCSG grant P30 CA010815. NR 34 TC 8 Z9 8 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-1471 EI 1755-148X J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD MAR PY 2015 VL 28 IS 2 BP 184 EP 195 DI 10.1111/pcmr.12330 PG 12 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA CF8OJ UT WOS:000352821100011 PM 25407936 ER PT J AU Sanhueza, M Chai, A Smith, C McCray, BA Simpson, TI Taylor, JP Pennetta, G AF Sanhueza, Mario Chai, Andrea Smith, Colin McCray, Brett A. Simpson, T. Ian Taylor, J. Paul Pennetta, Giuseppa TI Network Analyses Reveal Novel Aspects of ALS Pathogenesis SO PLOS GENETICS LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; ENDOPLASMIC-RETICULUM; UBIQUITIN LIGASES; VAPB INTERACTS; PROTEIN VAPB; DROSOPHILA-MELANOGASTER; CALCIUM HOMEOSTASIS; GENE-EXPRESSION; LIPID DROPLETS AB Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective loss of motor neurons, muscle atrophy and paralysis. Mutations in the human VAMP-associated protein B (hVAPB) cause a heterogeneous group of motor neuron diseases including ALS8. Despite extensive research, the molecular mechanisms underlying ALS pathogenesis remain largely unknown. Genetic screens for key interactors of hVAPB activity in the intact nervous system, however, represent a fundamental approach towards understanding the in vivo function of hVAPB and its role in ALS pathogenesis. Targeted expression of the disease-causing allele leads to neurodegeneration and progressive decline in motor performance when expressed in the adult Drosophila, eye or in its entire nervous system, respectively. By using these two phenotypic readouts, we carried out a systematic survey of the Drosophila genome to identify modifiers of hVAPB-induced neurotoxicity. Modifiers cluster in a diverse array of biological functions including processes and genes that have been previously linked to hVAPB function, such as proteolysis and vesicular trafficking. In addition to established mechanisms, the screen identified endocytic trafficking and genes controlling proliferation and apoptosis as potent modifiers of ALS8-mediated defects. Surprisingly, the list of modifiers was mostly enriched for proteins linked to lipid droplet biogenesis and dynamics. Computational analysis reveals that most modifiers can be linked into a complex network of interacting genes, and that the human genes homologous to the Drosophila modifiers can be assembled into an interacting network largely overlapping with that in flies. Identity markers of the endocytic process were also found to abnormally accumulate in ALS patients, further supporting the relevance of the fly data for human biology. Collectively, these results not only lead to a better understanding of hVAPB function but also point to potentially relevant targets for therapeutic intervention. C1 [Sanhueza, Mario; Chai, Andrea; Pennetta, Giuseppa] Univ Edinburgh, Ctr Integrat Physiol, Edinburgh, Midlothian, Scotland. [Sanhueza, Mario; Chai, Andrea; Pennetta, Giuseppa] Univ Edinburgh, Euan MacDonald Ctr Motor Neuron Dis Res, Edinburgh, Midlothian, Scotland. [Chai, Andrea] Baylor Coll Med, Jan & Dan Duncan Neurol Res Inst, Dept Mol & Human Genet, Houston, TX 77030 USA. [Smith, Colin] Univ Edinburgh, Acad Dept Neuropathol, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland. [McCray, Brett A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Cambridge, MA 02138 USA. [Simpson, T. Ian] Univ Edinburgh, Biomath & Stat Scotland, Edinburgh EH8 9YL, Midlothian, Scotland. [Simpson, T. Ian] Univ Edinburgh, Sch Informat, Inst Adapt & Neural Computat, Edinburgh EH8 9YL, Midlothian, Scotland. [Taylor, J. Paul] St Jude Childrens Res Hosp, Dept Cell & Mol Biol, Memphis, TN 38105 USA. RP Sanhueza, M (reprint author), Univ Edinburgh, Ctr Integrat Physiol, Edinburgh, Midlothian, Scotland. EM g.pennetta@ed.ac.uk RI Simpson, Ian/B-4722-2011 OI Simpson, Ian/0000-0003-0495-7187 FU Wellcome Trust [Pennetta8920]; Motor Neuron Disease Association [Pennetta6231]; MND Scotland Association [Pennetta40851] FX Our work was supported by a Wellcome Trust (http://www.wellcome.ac.uk) research grant (to GP, grant number: Pennetta8920), by a Motor Neuron Disease Association (http://www.mndassociation.org) fellowship (to GP, grant number: Pennetta6231) and by a MND Scotland Association (http://www.mndscotland.org.uk) fellowship (to GP, grant number: Pennetta40851). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 94 TC 9 Z9 9 U1 1 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD MAR PY 2015 VL 11 IS 3 AR e1005107 DI 10.1371/journal.pgen.1005107 PG 32 WC Genetics & Heredity SC Genetics & Heredity GA CE9XO UT WOS:000352197100072 PM 25826266 ER PT J AU Ye, L Morse, LR Zhang, L Sasaki, H Mills, JC Odgren, PR Sibbel, G Stanley, JRL Wong, G Zamarioli, A Battaglino, RA AF Ye, Liang Morse, Leslie R. Zhang, Li Sasaki, Hajime Mills, Jason C. Odgren, Paul R. Sibbel, Greg Stanley, James R. L. Wong, Gee Zamarioli, Ariane Battaglino, Ricardo A. TI Osteopetrorickets due to Snx10 Deficiency in Mice Results from Both Failed Osteoclast Activity and Loss of Gastric Acid-Dependent Calcium Absorption SO PLOS GENETICS LA English DT Article ID BONE MASS; MALIGNANT OSTEOPETROSIS; RESORBING OSTEOCLASTS; TARGETED DISRUPTION; CL-/HCO3-EXCHANGER; CELLS; TRAFFICKING; EXPRESSION; MUTATION; GENE AB Mutations in sorting nexin 10 (Snx10) have recently been found to account for roughly 4% of all human malignant osteopetrosis, some of them fatal. To study the disease pathogenesis, we investigated the expression of Snx10 and created mouse models in which Snx10 was knocked down globally or knocked out in osteoclasts. Endocytosis is severely defective in Snx10-deficent osteoclasts, as is extracellular acidification, ruffled border formation, and bone resorption. We also discovered that Snx10 is highly expressed in stomach epithelium, with mutations leading to high stomach pH and low calcium solubilization. Global Snx10-deficiency in mice results in a combined phenotype: osteopetrosis (due to osteoclast defect) and rickets (due to high stomach pH and low calcium availability, resulting in impaired bone mineralization). Osteopetrorickets, the paradoxical association of insufficient mineralization in the context of a positive total body calcium balance, is thought to occur due to the inability of the osteoclasts to maintain normal calcium-phosphorus homeostasis. However, osteoclast-specific Snx10 knockout had no effect on calcium balance, and therefore led to severe osteopetrosis without rickets. Moreover, supplementation with calcium gluconate rescued mice from the rachitic phenotype and dramatically extended life span in global Snx10-deficient mice, suggesting that this may be a life-saving component of the clinical approach to Snx10-dependent human osteopetrosis that has previously gone unrecognized. We conclude that tissue-specific effects of Snx10 mutation need to be considered in clinical approaches to this disease entity. Reliance solely on hematopoietic stem cell transplantation can leave hypocalcemia uncorrected with sometimes fatal consequences. These studies established an essential role for Snx10 in bone homeostasis and underscore the importance of gastric acidification in calcium uptake. C1 [Ye, Liang; Morse, Leslie R.; Zhang, Li; Battaglino, Ricardo A.] Forsyth Inst, Dept Mineralized Tissue Biol, Cambridge, MA 02142 USA. [Ye, Liang; Sasaki, Hajime; Battaglino, Ricardo A.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Morse, Leslie R.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Morse, Leslie R.] Spaulding Rehabil Hosp, Boston, MA USA. [Sasaki, Hajime] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA USA. [Mills, Jason C.; Sibbel, Greg] Washington Univ, Sch Med, Div Gastroenterol, Dept Med, St Louis, MO 63110 USA. [Odgren, Paul R.] Univ Massachusetts, Sch Med, Dept Cell & Dev Biol, Worcester, MA USA. [Stanley, James R. L.; Wong, Gee] CBSET Inc, Lexington, MA USA. [Zamarioli, Ariane] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biomech Med & Rehabil, Sao Paulo, Brazil. RP Ye, L (reprint author), Forsyth Inst, Dept Mineralized Tissue Biol, Cambridge, MA 02142 USA. EM rbattaglino@forsyth.org RI battaglino, ricardo/D-2892-2015; Zamarioli, Ariane/K-7001-2012; Morse, Leslie/C-9442-2015 OI Zamarioli, Ariane/0000-0002-7939-0528; Morse, Leslie/0000-0002-7426-6341 FU Advanced Imaging and Tissue Analysis Core of the Washington University Digestive Diseases Research Core Centers [NIH2P30 DK052574-12]; NIH from the National Institute of Diabetes and Digestive and Kidney [R01 DK094989-01]; NIH from the National Institute of Arthritis and Musculoskeletal and Skin Diseases [RO1 AR061504] FX This study was supported by the following grants: Advanced Imaging and Tissue Analysis Core of the Washington University Digestive Diseases Research Core Centers (NIH2P30 DK052574-12) to JCM, NIH R01 DK094989-01 from the National Institute of Diabetes and Digestive and Kidney to JCM, and NIH RO1 AR061504 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases to PRO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 2 Z9 3 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD MAR PY 2015 VL 11 IS 3 AR e1005057 DI 10.1371/journal.pgen.1005057 PG 25 WC Genetics & Heredity SC Genetics & Heredity GA CE9XO UT WOS:000352197100043 PM 25811986 ER PT J AU Cortese, BM Uhde, TW LaRowe, SD Stein, SV Freeman, WC McClernon, FJ Brady, KT Hartwell, KJ AF Cortese, Bernadette M. Uhde, Thomas W. LaRowe, Steven D. Stein, Sarah V. Freeman, W. Connor McClernon, F. Joseph Brady, Kathleen T. Hartwell, Karen J. TI Olfactory Cue Reactivity in Nicotine-Dependent Adult Smokers SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article DE smoking; odor cues; craving; tobacco dependence; cue reactivity ID IN-VIVO; SMOKING-CESSATION; ALCOHOLICS; GENDER; INDUCTION; DRINKERS; STIMULI; PLACEBO; TRIAL; SMELL AB Cue-elicited reactivity is a significant factor in relapse during smoking quit attempts. Previous research has focused primarily on visual smoking cues, with very limited research examining reactivity to olfactory triggers. Twenty-six adult non-treatment-seeking, nicotine-dependent smokers were exposed to 7 odorants during a cue-reactivity session measuring heart rate, skin conductance, and subjective craving. Cues included 2 cigarette odors (fresh tobacco and cigarette smoke), 2 odors previously identified as smoking-related (freshly mowed grass and coffee), 2 odors previously identified as unrelated to smoking (lavender and burned rubber), and 1 odorless control (propylene glycol). Pairwise comparisons demonstrated that subjective intensity of craving was significantly higher following exposure to the fresh tobacco odor compared with the odorless control (p < .01). A significant main effect for cue type on a physiological measure of arousal was also revealed, with a fresh tobacco odor-elicited significant increase in skin conductance level compared with the odorless control. However, no main effect of cue type on heart rate was found (p = .25). The results of the present study indicate that cigarette odor is an effective olfactory cue that heightens both subjective craving and increases skin conductance in smokers. Future research is needed to evaluate whether avoidance of these odors, or extinction of responses to them, can reduce relapse risk during smoking quit attempts. C1 [Cortese, Bernadette M.; Uhde, Thomas W.; LaRowe, Steven D.; Stein, Sarah V.; Freeman, W. Connor; Brady, Kathleen T.; Hartwell, Karen J.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [LaRowe, Steven D.; Brady, Kathleen T.; Hartwell, Karen J.] Ralph H Johnson VAMC, Charleston, SC USA. [McClernon, F. Joseph] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. RP Cortese, BM (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, MSC 861, Charleston, SC 29425 USA. EM corteseb@musc.edu FU Medical University of South Carolina's South Carolina Clinical and Translational Research Institute (SCTR) [UL1 RR029882]; NIMH [K01MH090548] FX This research was supported by the Medical University of South Carolina's South Carolina Clinical and Translational Research Institute (SCTR) Grant UL1 RR029882 (Karen J. Hartwell) and by NIMH Grant K01MH090548 (Bernadette M. Cortese). We thank Max Owens and Todd LeMatty for their assistance during data acquisition and the preparation of this article. We also thank ScentAir Corporation, Charlotte, NC for providing the odorants. NR 34 TC 3 Z9 3 U1 0 U2 3 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X EI 1939-1501 J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD MAR PY 2015 VL 29 IS 1 BP 91 EP 96 DI 10.1037/adb0000018 PG 6 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA CF1PD UT WOS:000352318200011 PM 25180553 ER PT J AU Meterko, M Restuccia, JD Stolzmann, K Mohr, D Brennan, C Glasgow, J Kaboli, P AF Meterko, Mark Restuccia, Joseph D. Stolzmann, Kelly Mohr, David Brennan, Caitlin Glasgow, Justin Kaboli, Peter TI RESPONSE RATES, NONRESPONSE BIAS, AND DATA QUALITY RESULTS FROM A NATIONAL SURVEY OF SENIOR HEALTHCARE LEADERS SO PUBLIC OPINION QUARTERLY LA English DT Article AB Survey response rate is regarded as a key data-quality indicator, yet response rate is not necessarily predictive of nonresponse bias. Our study objective was to use a high-response-rate survey to assess nonresponse bias across successive waves. This survey of healthcare leaders utilized a web-based, self-report format with an initial invitation and four nonrespondent follow-ups. Across five waves, comparisons were made for demographic and facility characteristics, proportion of items completed, and distribution of three question types: factual reports of customized categorical responses; single-item evaluations using five-point Likert scales; and multi-item scales, across four-or five-point Likert scales. The overall response rate was 95 percent (118/124); waves did not differ by demographic and facility characteristics or missing data. Across waves, there were no significant differences between responses to two factual report questions or the single-or multi-item scale measures of attitudes. According to a "what-if" analysis of cumulative results by wave, the same conclusions would have been reached if data collection had been halted at earlier points in time. Precision and statistical power increased as number of respondents accumulated by wave. The high response rate facilitated studying the impact of nonresponse bias by wave. Although high response rates are desirable because of precision and power, as survey fatigue increases, absolute thresholds representing "adequate" response rates may be less realistic. Results from "low" response-rate surveys should be considered on their merits, as they may accurately represent attitudes of the population. Therefore, low response rates should not be cited as reasons to dismiss results as uninformative. C1 [Meterko, Mark; Restuccia, Joseph D.; Stolzmann, Kelly; Mohr, David] Boston VA Healthcare Syst, CHOIR, Boston, MA USA. [Meterko, Mark; Mohr, David] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Restuccia, Joseph D.] Boston Univ, Sch Management, Boston, MA 02215 USA. [Brennan, Caitlin] NIH, Outcomes Management, Dept Nursing Res & Practice Dev, Ctr Clin, Bethesda, MD 20892 USA. [Glasgow, Justin] Christiana Care Hlth Syst, Wilmington, DE USA. [Kaboli, Peter] Iowa City VAMC, CADRE Ctr, Iowa City, IA 52246 USA. [Kaboli, Peter] Univ Iowa, Carver Coll Med, Internal Med, Iowa City, IA USA. RP Kaboli, P (reprint author), Iowa City VAMC, CADRE Ctr, Mailstop 152,601 Highway West, Iowa City, IA 52246 USA. EM peter.kaboli@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSRD) Service [REA 09-220]; Comprehensive Access & Delivery Research and Evaluation (CADRE) Center at the Iowa City VAMC [CIN 13-412]; HSR&D Center for Healthcare Organization and Implementation Research (CHOIR) at the Boston VA Healthcare System [HFP 04-145] FX MARK METERKO is an investigator at the Center for Healthcare Organization and Implementation Research (CHOIR) at the Boston VA Healthcare System, Boston, MA, USA, and research associate professor at the Boston University School of Public Health, Boston, MA, USA. JOSEPH D. RESTUCCIA is an investigator at the Center for Healthcare Organization and Implementation Research (CHOIR) at the Boston VA Healthcare System, Boston, MA, USA, and professor at the Boston University School of Management, Boston, MA, USA. KELLY STOLZMANN is a research analyst at the Center for Healthcare Organization and Implementation Research (CHOIR) at the Boston VA Healthcare System, Boston, MA, USA. DAVID MOHR is an investigator at the Center for Healthcare Organization and Implementation Research (CHOIR) at the Boston VA Healthcare System, Boston, MA, USA, and research assistant professor at the Boston University School of Public Health, Boston, MA, US. CAITLIN BRENNAN is Program Director for Outcomes Management, Department of Nursing Research and Practice Development, National Institutes of Health Clinical Center, Bethesda, MD, USA. JUSTIN GLASGOW is an internal medicine resident at Christiana Care Health System, Wilmington, DE, USA. PETER KABOLI is an investigator at the Comprehensive Access and Delivery Research and Evaluation (CADRE) Center at the Iowa City VA Healthcare System, Iowa City, IA, USA, and professor of internal medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA. The work reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) Service [REA 09-220 to M.M., J.D.R., K.S., D.M., and P.K.], the Comprehensive Access & Delivery Research and Evaluation (CADRE) Center at the Iowa City VAMC [CIN 13-412 to P.K. and J.G.], and the HSR&D Center for Healthcare Organization and Implementation Research (CHOIR) at the Boston VA Healthcare System [HFP 04-145 to M.M., J.D.R., K.S., D.M., and C.B.]. The authors wish to thank Errol Baker, Erol Pekoz, and Michael Shwartz for their thoughtful advice regarding sampling, population, and power analysis issues associated with this study. All three individuals are affiliated with the Center for Healthcare Organization and Implementation Research (CHOIR), VA Boston Healthcare System. Views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. *Address correspondence to Peter J. Kaboli, MD, MS, Iowa City VAMC, Comprehensive Access & Delivery Research and Evaluation (CADRE) Center, Mailstop 152, 601 Highway West, Iowa City, IA 52246, USA; e-mail: peter.kaboli@va.gov. NR 17 TC 1 Z9 1 U1 3 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0033-362X EI 1537-5331 J9 PUBLIC OPIN QUART JI Public Opin. Q. PD SPR PY 2015 VL 79 IS 1 BP 130 EP 144 DI 10.1093/poq/nfu052 PG 15 WC Communication; Political Science; Social Sciences, Interdisciplinary SC Communication; Government & Law; Social Sciences - Other Topics GA CF4RE UT WOS:000352537500006 ER PT J AU Manian, FA AF Manian, Farrin A. TI Time to Dedifferentiate SO SOUTHERN MEDICAL JOURNAL LA English DT Editorial Material ID EDUCATION C1 [Manian, Farrin A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Manian, FA (reprint author), Dept Med, 50 Staniford St,Suite 503 B, Boston, MA 02114 USA. EM Fmanian@mgh.harvard.edu NR 9 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0038-4348 EI 1541-8243 J9 SOUTH MED J JI South.Med.J. PD MAR PY 2015 VL 108 IS 3 BP 198 EP 199 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CF4FV UT WOS:000352505100012 PM 25772056 ER PT J AU Satyanarayana, G Hammond, SP Broge, TA Mackenzie, MR Viscidi, R Politikos, I Koralnik, IJ Cutler, CS Ballen, K Boussiotis, V Marty, FM Tan, CS AF Satyanarayana, Gowri Hammond, Sarah P. Broge, Thomas A., Jr. Mackenzie, Matthew R. Viscidi, Raphael Politikos, Ioannis Koralnik, Igor J. Cutler, Corey S. Ballen, Karen Boussiotis, Vassiliki Marty, Francisco M. Tan, Chen Sabrina TI BK polyomavirus reactivation after reduced-intensity double umbilical cord blood cell transplantation SO TRANSPLANT IMMUNOLOGY LA English DT Article DE BK polyomavirus; Hemorrhagic cystitis; Viral reactivation ID BONE-MARROW-TRANSPLANTATION; HEMORRHAGIC CYSTITIS; VIRUS-INFECTION; IMMUNE RECONSTITUTION; RECIPIENTS; NEPHROPATHY; ASSOCIATION; DISEASE; LOAD AB Serial serum samples from 27 patients who underwent double umbilical cord blood transplantation (dUCBT) were analyzed for BK polyomavirus (BKPyV) DNA by real-time PCR and BKPyV-specific immune globulin by ELISA. Clinical data were collected on all patients. All pre-transplant sera had detectable anti-BKPyV IgG. Fifteen patients (56%) had detectable serum BKPyV DNA (median 8.9 x 10(4) copies/ml; range 4.1 x 10(3)-7.9 x 10(6) copies/ml) a median of 40 days (range, 27-733 days) after dUCBT, with highest viral loads on Day 100 assessment. The cumulative probability of developing BKPyV viremia by Day 100 was 0.52 (95% CI, 033-0.71). Six of 15 patients with BKPyV viremia experienced hemorrhagic cystitis by Day 100. By Day 100, there was a trend towards higher BKPyV viral loads in sera of patients with hemorrhagic cystitis than in those BKPyV viremic patients without hemorrhagic cystitis (p = 0.06). BKPyV viremia was associated with significantly higher anti-BKPyV IgM values at 6 months post-dUCBT (P = 0.003). BKPyV viremia occurs early after dUBCT and is associated with a detectable humoral immune response by 6 months post-dUBCT. (C) 2014 Elsevier B.V. All rights reserved. C1 [Satyanarayana, Gowri; Tan, Chen Sabrina] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Broge, Thomas A., Jr.; Mackenzie, Matthew R.; Koralnik, Igor J.; Tan, Chen Sabrina] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA. [Satyanarayana, Gowri] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. [Broge, Thomas A., Jr.; Mackenzie, Matthew R.; Politikos, Ioannis; Koralnik, Igor J.; Boussiotis, Vassiliki; Tan, Chen Sabrina] Beth Israel Deaconess Med Ctr, Dept Neurol, Div Neurovirol, Boston, MA 02215 USA. [Satyanarayana, Gowri; Hammond, Sarah P.; Marty, Francisco M.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Viscidi, Raphael] Johns Hopkins Univ, Med Ctr, Div Dev Neurovirol, Baltimore, MD 21218 USA. [Cutler, Corey S.; Marty, Francisco M.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Ballen, Karen] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Tan, CS (reprint author), Beth Israel Deaconess Med Ctr, E-CLS 1011,330 Brookline Ave, Boston, MA 02215 USA. EM ctan@bidmc.hanrard.edu FU NIH grant [R01 NS 047029, NS 074995, NS R56 041198, K24 NS 060950, K08 NS 064215-01]; Harvard Catalyst/The Harvard Clinical and Translational Science Center (NCRR); Harvard Catalyst/The Harvard Clinical and Translational Science Center (NCATS); Harvard Catalyst/The Harvard Clinical and Translational Science Center (NIH Award) [UL1 TR001102]; Harvard University FX This work was conducted in part with support from NIH grants R01 NS 047029 and NS 074995, NS R56 041198, and K24 NS 060950 to IJK, and NIH grant K08 NS 064215-01 to CST.; This work was conducted with support from Harvard Catalyst/The Harvard Clinical and Translational Science Center (NCRR and NCATS, NIH Award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic healthcare centers. NR 32 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0966-3274 EI 2210-3384 J9 TRANSPL IMMUNOL JI Transpl. Immunol. PD MAR PY 2015 VL 32 IS 2 BP 116 EP 120 DI 10.1016/j.trim.2014.12.002 PG 5 WC Immunology; Transplantation SC Immunology; Transplantation GA CG1YT UT WOS:000353072800009 PM 25536223 ER PT J AU Maughan, BC Seigel, TA Napoli, AM AF Maughan, Brandon C. Seigel, Todd A. Napoli, Anthony M. TI PLETH VARIABILITY INDEX AND FLUID RESPONSIVENESS OF HEMODYNAMICALLY STABLE PATIENTS AFTER CARDIOTHORACIC SURGERY SO AMERICAN JOURNAL OF CRITICAL CARE LA English DT Article ID CARDIOPULMONARY BYPASS; CARDIAC-SURGERY; PREDICTION AB Background Fluid responsiveness is a measure of preload dependence and is defined as an increase in cardiac output due to volume expansion. Recent publications have suggested that variation in amplitude of the pulse oximetry waveform may be predictive of fluid responsiveness. The pleth variability index (PVI) was developed as a noninvasive bedside measurement of this variation in the pulse oximetry waveform. Objectives To measure the discriminatory value of PVI for predicting fluid responsiveness as measured by pulmonary artery catheter thermodilution in patients after cardiothoracic surgery. Methods A prospective observational study of hemodynamically stable postoperative cardiac surgery patients with pulmonary artery catheters. A fingertip sensor was used to measure PVI. Vital signs, PVI, and cardiac index were measured before, during, and after passive leg raise. Fluid responsiveness was defined by increase in cardiac index of greater than 15% during passive leg raise. The discriminatory value of PVI was assessed by using the Wilcoxon method to measure the area under the receiver operating curve. Results In 13 months, 47 patients (24 receiving mechanical ventilation, 23 spontaneously breathing) were enrolled. Fluid responsiveness was noted in 42% of intubated patients and 48% of spontaneously breathing patients. PVI was not adequate to discriminate fluid responsiveness in intubated patients (area under curve, 0.63; P=.16) or spontaneously breathing patients (area under curve, 0.41; P=.75). Conclusions Among postoperative cardiac surgery patients, PVI is not reliable for predicting fluid responsiveness as measured by pulmonary artery catheter thermodilution, regardless of ventilatory status. C1 Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Dept Emergency Med, Providence, RI 02912 USA. [Maughan, Brandon C.] Univ Penn, Vet Affairs Med Ctr, Robert Wood Johnson Clin Scholar Philadelphia, Philadelphia, PA 19104 USA. [Seigel, Todd A.] Kaiser Oakland Med Ctr, Dept Emergency Med & Crit Care, Oakland, CA USA. [Napoli, Anthony M.] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Providence, RI 02912 USA. RP Maughan, BC (reprint author), Univ Penn, 423 Guardian Ave,Blockley Hall 1303A, Philadelphia, PA 19104 USA. EM Brandon.Maughan@uphs.upenn.edu NR 14 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1062-3264 EI 1937-710X J9 AM J CRIT CARE JI Am. J. Crit. Care PD MAR 1 PY 2015 VL 24 IS 2 BP 172 EP 175 DI 10.4037/ajcc2015864 PG 4 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA CE8XL UT WOS:000352127300011 PM 25727278 ER PT J AU Yanke, E Zellmer, C Van Hoof, S Moriarty, H Carayon, P Safdar, N AF Yanke, Eric Zellmer, Caroline Van Hoof, Sarah Moriarty, Helene Carayon, Pascale Safdar, Nasia TI Understanding the current state of infection prevention to prevent Clostridium difficile infection: A human factors and systems engineering approach SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Clostridium difficile; Contact precautions; Infection control; Human factors; Systems engineering ID HAND HYGIENE COMPLIANCE; HEALTH-CARE WORKERS; CONTACT PRECAUTIONS; PATIENT SAFETY; BURDEN; VISITORS; DIARRHEA AB Background: Achieving and sustaining high levels of health care worker (HCW) compliance with contact isolation precautions is challenging. The aim of this study was to determine HCW work system barriers to and facilitators of adherence to contact isolation for patients with suspected or confirmed Clostridium difficile infection (CDI) using a human factors and systems engineering approach. Methods: This prospective cohort study took place between September 2013 and November 2013 at a large academic medical center (hospital A) and an affiliated Veterans Administration hospital (hospital B). A human factors engineering (HFE) model for patient safety, the Systems Engineering Initiative for Patient Safety model, was used to guide work system analysis and direct observation data collection. There were 288 observations conducted. HCWs and visitors were assessed for compliance with all components of contact isolation precautions (hand hygiene, gowning, and gloving) before and after patient contact. Time required to complete contact isolation precautions was measured, and adequacy of contact isolation supplies was assessed. Results: Full compliance with contact isolation precautions was low at both hospitals A (7%) and B (22%). Lack of appropriate hand hygiene prior to room entry (compliance for hospital A: 18%; compliance for hospital B: 29%) was the most common reason for lack of full compliance. More time was required for full compliance compared with compliance with no components of contact isolation precautions before patient room entry, inside patient room, and after patient room exit (59.9 vs 3.2 seconds, P <. 001; 507.3 vs 149.7 seconds, P = .006; 15.2 vs 1.3 seconds, P <.001, respectively). Compliance was lower when contact isolation supplies were inadequate (4% vs 16%, P = .005). Conclusions: Adherence to contact isolation precautions for CDI is a complex, time-consuming process. HFE analysis indicates that multiple work system components serve as barriers and facilitators to full compliance with contact isolation precautions and should be addressed further to prevent CDI. Published by Elsevier Inc. on behalf of the Association for Professionals in Infection Control and Epidemiology, Inc. C1 [Yanke, Eric] William S Middleton Mem Vet Adm Med Ctr, Dept Med, Madison, WI USA. [Zellmer, Caroline] Univ Wisconsin, Coll Agr & Life Sci, Madison, WI 53706 USA. [Van Hoof, Sarah] Univ Wisconsin Hosp & Clin, Dept Infect Control, Madison, WI 53792 USA. [Moriarty, Helene] Villanova Univ, Coll Nursing, Villanova, PA 19085 USA. [Moriarty, Helene] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Carayon, Pascale] Univ Wisconsin, Dept Ind & Syst Engn, Ctr Qual & Prod Improvement, Madison, WI USA. [Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Safdar, Nasia] Univ Wisconsin, Sch Med, Dept Med, Div Infect Dis, Madison, WI USA. [Safdar, Nasia] Univ Wisconsin, Infect Control Dept, Madison, WI USA. RP Safdar, N (reprint author), UWMF Centennial Bldg,1685 Highland Ave, Madison, WI 53705 USA. EM ns2@medicine.wisc.edu FU Veterans Affairs MERIT award; University of Wisconsin Institute for Clinical and Translational Research; Clinical and Translational Science Award program; National Center for Advancing Translational Sciences [9U54TR000021] FX Dr. Safdar is supported by a Veterans Affairs MERIT award. Dr. Carayon is supported by the University of Wisconsin Institute for Clinical and Translational Research and the Clinical and Translational Science Award program, previously through the National Center for Research Resources (grant no. 1UL1RR025011), and now by the National Center for Advancing Translational Sciences (grant no. 9U54TR000021). NR 23 TC 6 Z9 6 U1 3 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 EI 1527-3296 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD MAR PY 2015 VL 43 IS 3 BP 241 EP 247 DI 10.1016/j.ajic.2014.11.026 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA CE8PQ UT WOS:000352106200006 PM 25728149 ER PT J AU Khan, A Rao, A Reyes-Sacin, C Hayakawa, K Szpunar, S Riederer, K Kaye, K Fishbain, JT Levine, D AF Khan, Amber Rao, Amitha Reyes-Sacin, Carlos Hayakawa, Kayoko Szpunar, Susan Riederer, Kathleen Kaye, Keith Fishbain, Joel T. Levine, Diane TI Use of portable electronic devices in a hospital setting and their potential for bacterial colonization SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Mobile electronic devices; Contamination ID MOBILE PHONES; CONTAMINATION; PHYSICIANS AB Portable electronic devices are increasingly being used in the hospital setting. As with other fomites, these devices represent a potential reservoir for the transmission of pathogens. We conducted a convenience sampling of devices in 2 large medical centers to identify bacterial colonization rates and potential risk factors. Copyright (C) 2015 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. C1 [Khan, Amber; Levine, Diane] Detroit Med Ctr, Dept Internal Med, Detroit, MI USA. [Khan, Amber; Kaye, Keith; Levine, Diane] Wayne State Univ, Sch Med, Detroit, MI USA. [Rao, Amitha] Michael E Debakey Vet Adm Med Ctr, Dept Primary Care Med, Houston, TX USA. [Reyes-Sacin, Carlos] Med AIDS Outreach Alabama, Dept Infect Dis, Montgomery, AL USA. [Hayakawa, Kayoko] Natl Ctr Global Hlth & Med, Dis Control & Prevent Ctr, Tokyo, Japan. [Szpunar, Susan; Riederer, Kathleen] St John Hosp & Med Ctr, Dept Grad Med Educ, Detroit, MI USA. [Kaye, Keith] St John Hosp & Med Ctr, Div Infect Dis, Dept Internal Med, Detroit, MI USA. [Fishbain, Joel T.] Detroit Med Ctr, Div Infect Dis, Detroit, MI USA. RP Khan, A (reprint author), Detroit Receiving Hosp & Univ Hlth Ctr, 4201 St Antoine,UHC 2E, Detroit, MI 48201 USA. EM amkha@med.wayne.edu NR 7 TC 3 Z9 3 U1 2 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 EI 1527-3296 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD MAR PY 2015 VL 43 IS 3 BP 286 EP 288 DI 10.1016/j.ajic.2014.11.013 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA CE8PQ UT WOS:000352106200015 PM 25557772 ER PT J AU Lee, JH Cho, MH Hersh, CP McDonald, MLN Wells, JM Dransfield, MT Bowler, RP Lynch, DA Lomas, DA Crapo, JD Silverman, EK AF Lee, Jin Hwa Cho, Michael H. Hersh, Craig P. McDonald, Merry-Lynn N. Wells, J. Michael Dransfield, Mark T. Bowler, Russell P. Lynch, David A. Lomas, David A. Crapo, James D. Silverman, Edwin K. CA COPDGene Investigators ECLIPSE Investigators TI IREB2 and GALC Are Associated with Pulmonary Artery Enlargement in Chronic Obstructive Pulmonary Disease SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE chronic obstructive pulmonary disease; genome-wide association; pulmonary hypertension; subtyping ID GENOME-WIDE ASSOCIATION; AIR-FLOW OBSTRUCTION; IRON HOMEOSTASIS; LUNG TRANSPLANTATION; CHRONIC-BRONCHITIS; COPD PATIENTS; HYPERTENSION; EMPHYSEMA; SUSCEPTIBILITY; METAANALYSIS AB Pulmonary hypertension is associated with advanced chronic obstructive pulmonary disease (COPD), although pulmonary vascular changes occur early in the course of the disease. Pulmonary artery (PA) enlargement (PAE) measured by computed tomography correlates with pulmonary hypertension and COPD exacerbation frequency. Genome-wide association studies of PAE in subjects with COPD have not been reported. To investigate whether genetic variants are associated with PAE within subjects with COPD, we investigated data from current and former smokers from the COPDGene Study and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study. The ratio of the diameter of the PA to the diameter of the aorta (A) was measured using computed tomography. PAE was defined as PA/A greater than 1. A genome-wide association study for COPD with PAE was performed using subjects with COPD without PAE (PA/A <= 1) as a control group. A secondary analysis used smokers with normal spirometry as a control group. Genotyping was performed on Illumina platforms. The results were summarized using fixed-effect meta-analysis. Both meta-analyses revealed a genome-wide significant locus on chromosome 15q25.1 in IREB2 (COPD with versus without PAE, rs7181486; odds ratio [OR] = 1.32; P = 2.10 x 10(-8); versus smoking control subjects, rs2009746; OR = 1.42; P= 1.32 x 10(-9)). PAE was also associated with a region on 14q31.3 near the GALC gene (rs7140285; OR = 1.55; P = 3.75 x 10(-8)). Genetic variants near IREB2 and GALC likely contribute to genetic susceptibility to PAE associated with COPD. This study provides evidence for genetic heterogeneity associated with a clinically important COPD vascular subtype. C1 [Lee, Jin Hwa; Cho, Michael H.; Hersh, Craig P.; McDonald, Merry-Lynn N.; Silverman, Edwin K.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Cho, Michael H.; Hersh, Craig P.; Silverman, Edwin K.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Lee, Jin Hwa] Ewha Womans Univ, Sch Med, Dept Internal Med, Div Pulm & Crit Care Med, Seoul, South Korea. [Wells, J. Michael; Dransfield, Mark T.] Univ Alabama Birmingham, Lung Hlth Ctr, Div Pulm Allergy & Crit Care, Birmingham, AL USA. [Wells, J. Michael; Dransfield, Mark T.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Bowler, Russell P.; Lynch, David A.; Crapo, James D.] Natl Jewish Hlth, Div Pulm & Crit Care, Denver, CO USA. [Lomas, David A.] UCL, Wolfson Inst Biomed Res, London, England. RP Silverman, EK (reprint author), Brigham & Womens Hosp, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. EM jinhwalee@ewha.ac.kr; ed.silverman@channing.harvard.edu RI Agusti Garcia-Navarro, Alvar/F-4474-2015; Mattheisen, Manuel/B-4949-2012; Coxson, Harvey/A-9861-2017 OI MacNee, William/0000-0002-3692-1448; Comellas, Alejandro/0000-0003-1521-7520; Agusti Garcia-Navarro, Alvar/0000-0003-3271-3788; Mattheisen, Manuel/0000-0002-8442-493X; Coxson, Harvey/0000-0001-5750-9711 FU National Institutes of Health [R01 HL089856, R01 HL075478, R01HL089897, P01 HL105339, K08 HL097029, R01 HL113264]; COPD Foundation; GSK FX This work was supported by National Institutes of Health grants R01 HL089856 (E.K.S.), R01 HL075478 (E.K.S), R01HL089897 (J.D.C.), P01 HL105339 (E.K.S.), K08 HL097029 (M.H.C), and R01 HL113264 (M.H.C.). The COPDGene study (NCT00608764) is also supported by the COPD Foundation through contributions made to an industry advisory board comprised of AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer, Siemens, Sunovion and GlaxoSmithKline (GSK). The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study (NCT00292552; GSK code SCO104960) was sponsored by GSK. NR 56 TC 3 Z9 4 U1 1 U2 5 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 MAR PY 2015 VL 52 IS 3 BP 365 EP 376 DI 10.1165/rcmb.2014-0210OC PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA CF0BS UT WOS:000352208100010 PM 25101718 ER PT J AU Thaler, NS Sayegh, P Kim, MS Castellon, SA Hinkin, CH AF Thaler, Nicholas S. Sayegh, Philip Kim, Michelle S. Castellon, Steven A. Hinkin, Charles H. TI Interactive Effects of Neurocognitive Impairment and Substance Use on Antiretroviral Non-adherence in HIV Disease SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE HIV/AIDS; Drug and alcohol abuse ID MEDICATION ADHERENCE; NEUROPSYCHOLOGICAL IMPAIRMENT; INFECTED INDIVIDUALS; DEPRESSIVE SYMPTOMS; PROSPECTIVE MEMORY; VIRAL SUPPRESSION; DRUG-USE; ADULTS; METHAMPHETAMINE; PREDICTORS AB While numerous studies have established the adverse independent effects of clinical conditions including neurocognitive dysfunction, psychiatric illness, and substance abuse/dependence on medication adherence among HIV-infected adults, fewer have studied their interactive effects. The current study examined this issue among 204 HIV-infected participants based upon current neurocognitive functioning and DSM-IV-diagnosed psychiatric illness and current substance abuse or dependence. Results confirmed that participants with any of these risk factors demonstrated poorer adherence than individuals with no risk factors. A neurocognitive status x substance abuse/dependence interaction was also identified such that participants with impaired neurocognition and a co-occurring substance abuse/dependence diagnosis demonstrated the poorest adherence. Results confirm the deleterious impact of these risk factors in isolation and also identify a specific interactive effect for individuals with comorbid neurocognitive impairment and a substance abuse/dependence disorder. Findings highlight the need for interventions that simultaneously address these problems. C1 [Thaler, Nicholas S.; Sayegh, Philip; Castellon, Steven A.; Hinkin, Charles H.] Univ Calif Los Angeles, Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Kim, Michelle S.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Castellon, Steven A.; Hinkin, Charles H.] VA Greater Los Angeles Healthcare Syst, Dept Psychol, Los Angeles, CA USA. RP Thaler, NS (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, 760 Westwood Plaza,C8-735, Los Angeles, CA 90024 USA. EM Nthaler@mednet.ucla.edu FU National Institutes of Health [R01 DA13799]; National Institutes of Health Ruth L. Kirschstein National Research Service award [T32 MH19535] FX This work was supported by National Institutes of Health grant R01 DA13799 and the National Institutes of Health Ruth L. Kirschstein National Research Service award T32 MH19535. NR 35 TC 3 Z9 3 U1 3 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD MAR PY 2015 VL 30 IS 2 BP 114 EP 121 DI 10.1093/arclin/acu092 PG 8 WC Psychology, Clinical; Psychology SC Psychology GA CF0JP UT WOS:000352230000003 PM 25589442 ER PT J AU Gil, M Kawai, T Ishikawa-Nagai, S Da Silva, J Nagai, M AF Gil, Mindy Kawai, Toshihisa Ishikawa-Nagai, Shigemi Da Silva, John Nagai, Masazumi TI Identification of putative bone anabolic peptides targeting adherent plasma membrane SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Peptide display library; Adherent plasma membrane; Bone matrix; Biomaterial; Osteoblast; Differentiation ID VIVO PHAGE DISPLAY; EXTRACELLULAR-MATRIX; DIFFERENTIATION; REPAIR AB Bone matrix provides unknown essential cues for osteoblast lineage cells to develop, grow, repair and remodel bones via adherent plasma membrane. Because of its tight sealing with bone matrix in vivo and culture surface in vitro as well, the adherent plasma membrane has been unveiled target of investigation to date. Herein, we report a new approach to explore the adherence plasma membrane of osteoblasts with biofunctional peptide candidates in a bacterial peptide library. To accomplish this, human osteoblast like hFOB 1.19 cells were cultured on porous filter with 8 gm pore through which bacterial peptides were allowed to meet the membrane for affinity selection. The affinity-selected peptides were coated on culture plate to further evaluate their influence on osteoblastic cell adhesion, as well as expressions of osteoblast differentiation markers, alkaline phosphatase and osteocalcin. Finally, the serial screenings identified two prominent active peptides that enhanced the differentiation markers nearly to the same level as a control peptide of bone morphogenetic protein-2. Osteogenic activity is expected for the peptides when immobilized on bone implant surface. (C) 2015 Elsevier Inc. All rights reserved. C1 [Gil, Mindy; Kawai, Toshihisa] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Kawai, Toshihisa; Nagai, Masazumi] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA 02142 USA. [Ishikawa-Nagai, Shigemi; Da Silva, John] Harvard Univ, Sch Dent Med, Restorat Dent & Biomat Sci, Boston, MA 02115 USA. RP Nagai, M (reprint author), Forsyth Inst, Dept Immunol & Infect Dis, 245 First St, Cambridge, MA 02142 USA. EM mnagai@forsyth.org FU ITT Foundation, Basel, Switzerland [673_2009]; American Academy of Implant Dentistry Foundation (Student Research Grant) FX This study was supported by the ITT Foundation, Basel, Switzerland (673_2009) and the American Academy of Implant Dentistry Foundation (Student Research Grant). NR 16 TC 1 Z9 1 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR PY 2015 VL 459 IS 1 BP 71 EP 74 DI 10.1016/j.bbrc.2015.02.071 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CE8UU UT WOS:000352120400012 PM 25721672 ER PT J AU Purdy, E Thoma, B Bednarczyk, J Migneault, D Sherbino, J AF Purdy, Eve Thoma, Brent Bednarczyk, Joseph Migneault, David Sherbino, Jonathan TI The use of free online educational resources by Canadian emergency medicine residents and program directors SO CANADIAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE open educational resources; medical education; social media ID SOCIAL MEDIA; GENERATION; FOAM AB Introduction: Online educational resources (OERs) are increasingly available for emergency medicine (EM) education. This study describes and compares the use of free OERs by the Royal College of Physicians and Surgeons of Canada (RCPSC) EM residents and program directors (PDs) and investigates the relationship between the use of OERs and peer-reviewed literature. Methods: A bilingual, online survey was distributed to RCPSC-EM residents and PDs using a modified Dillman method. The chi-square test and Fisher's exact test were used to compare the responses of residents and PDs. Results: The survey was completed by 214/350 (61%) residents and 11/14 (79%) PDs. Free OERs were used by residents most frequently for general EM education (99.5%), procedural skills training (96%), and learning to interpret diagnostic tests (92%). OER modalities used most frequently included wikis (95%), file-sharing websites (95%), e-textbooks (94%), and podcasts (91%). Residents used wikis, podcasts, vodcasts, and file-sharing websites significantly more frequently than PDs. Relative to PDs, residents found entertainment value to be more important for choosing OERs (p< 0.01). Some residents (23%) did not feel that literature references were important, whereas all PDs did. Both groups reported that OERs increased the amount of peer-reviewed literature (75% and 60%, respectively) that they read. Conclusions: EM residents make extensive use of OERs and differ from their PDs in the importance that they place on their entertainment value and incorporation of peer-reviewed references. OERs may increase the use of peer-reviewed literature in both groups. Given the prevalence of OER use for core educational goals among RCPSC-EM trainees, future efforts to facilitate critical appraisal and appropriate resource selection are warranted. C1 [Purdy, Eve] Queens Univ, Sch Med, Kingston, ON, Canada. [Thoma, Brent] Massachusetts Gen Hosp, Dept Emergency Med, Learning Lab, Boston, MA 02114 USA. [Thoma, Brent] Massachusetts Gen Hosp, Dept Emergency Med, Div Med Simulat, Boston, MA 02114 USA. [Thoma, Brent] Univ Saskatchewan, Emergency Med, Saskatoon, SK, Canada. [Bednarczyk, Joseph] Univ Manitoba, Dept Emergency Med, Winnipeg, MB, Canada. [Migneault, David] Univ British Columbia, Dept Emergency Med, Vancouver, BC V5Z 1M9, Canada. [Sherbino, Jonathan] McMaster Univ, Div Emergency Med, Hamilton, ON, Canada. RP Thoma, B (reprint author), Royal Univ Hosp, Emergency Med Residency Program, Room 2686,103 Hosp Dr, Saskatoon, SK S7N 0W8, Canada. EM brent.thoma@usask.ca OI Thoma, Brent/0000-0003-1124-5786 NR 24 TC 12 Z9 12 U1 0 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1481-8035 EI 1481-8043 J9 CAN J EMERG MED JI Can. J. Emerg. Med. PD MAR PY 2015 VL 17 IS 2 BP 101 EP 106 DI 10.1017/cem.2014.73 PG 6 WC Emergency Medicine SC Emergency Medicine GA CE8LY UT WOS:000352095100001 PM 25927253 ER PT J AU Atkinson, P Bowra, J Lambert, M Lamprecht, H Noble, V Jarman, B AF Atkinson, Paul Bowra, Justin Lambert, Mike Lamprecht, Hein Noble, Vicki Jarman, Bob TI International Federation for Emergency Medicine Point of Care Ultrasound Curriculum SO CANADIAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE Point of Care Ultrasound; International Curriculum; Education; Competency Assessment AB To meet a critical and growing need for a standardized approach to emergency point of care ultrasound (PoCUS) worldwide, emergency physicians must be trained to deliver and teach this skill in an accepted and reliable format. Currently, there is no globally recognized, standard PoCUS curriculum that defines the accepted applications, as well as standards for training and practice of PoCUS by specialists and trainees in emergency medicine. To address this deficit, the International Federation for Emergency Medicine (IFEM) convened a sub-committee of international experts in PoCUS to outline a curriculum for training of specialists in emergency PoCUS. This curriculum document represents the consensus of recommendations by this sub-committee. The curriculum is designed to provide a framework for PoCUS education in emergency medicine. The focus is on the processes required to select core and enhanced applications, as well as the key elements required for the delivery of PoCUS training from introduction through to continuing professional development and skill maintenance. It is designed not to be prescriptive but to assist educators and emergency medicine leadership to advance PoCUS education in emergency medicine no matter the training venue. The content of this curriculum is relevant not just for communities with mature emergency medicine systems but in particular for developing nations or for nations seeking to develop PoCUS training programs within the current educational structure. We anticipate that there will be wide variability in how this curriculum is implemented and taught, reflecting the existing educational environment, resources and goals of educational programs. C1 [Atkinson, Paul] Dalhousie Univ, Halifax, NS, Canada. [Atkinson, Paul] St Johns Hosp, St John, NB, Canada. [Bowra, Justin] Sydney Adventist Hosp, Wahroonga, NSW, Australia. [Bowra, Justin] Univ Sydney, Sydney, NSW 2006, Australia. [Lambert, Mike] Advocate Christ Med Ctr, Dept Emergency Med, Oak Lawn, IL USA. [Lamprecht, Hein] Univ Stellenbosch, Joint Div Emergency Med, ZA-7600 Stellenbosch, South Africa. [Lamprecht, Hein] Univ Cape Town, ZA-7925 Cape Town, South Africa. [Noble, Vicki] Massachusetts Gen Hosp, Div Emergency Ultrasound, Boston, MA 02114 USA. [Noble, Vicki] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Jarman, Bob] Royal Victoria Infirm, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [Jarman, Bob] Univ Teesside, Middlesbrough, Cleveland, England. RP Atkinson, P (reprint author), Care of Reardon C, Int Federat Emergency Med, 34 Jeffcott St, W Melbourne, Vic 3003, Australia. EM ifem@acem.org.au NR 0 TC 4 Z9 4 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1481-8035 EI 1481-8043 J9 CAN J EMERG MED JI Can. J. Emerg. Med. PD MAR PY 2015 VL 17 IS 2 BP 161 EP 170 DI 10.1017/cem.2015.8 PG 10 WC Emergency Medicine SC Emergency Medicine GA CE8LY UT WOS:000352095100019 PM 26052968 ER PT J AU Thoma, B Chan, T Desouza, N Lin, M AF Thoma, Brent Chan, Teresa Desouza, Natalie Lin, Michelle TI Implementing peer review at an emergency medicine blog: bridging the gap between educators and clinical experts SO CANADIAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE knowledge translation; medical blog; medical education; peer review ID KNOWLEDGE TRANSLATION AB Emergency physicians are leaders in the "free open-access meducation" (FOAM) movement. The mandate of FOAM is to create open-access education and knowledge translation resources for trainees and practicing physicians (e.g., blogs, podcasts, and vodcasts). Critics of FOAM have suggested that because such resources can be easily published online without quality control mechanisms, unreviewed FOAM resources may be erroneous or biased. We present a new initiative to incorporate open, expert, peer review into an established academic medical blog. Experts provided either pre- or postpublication reviews that were visible to blog readers. This article outlines the details of this initiative and discusses the potentially transformative impact of this educational innovation. C1 [Thoma, Brent] Massachusetts Gen Hosp, Dept Emergency Med, Learning Lab, Boston, MA 02114 USA. [Thoma, Brent] Massachusetts Gen Hosp, Dept Emergency Med, Div Med Simulat, Boston, MA 02114 USA. [Thoma, Brent] Univ Saskatchewan, Dept Emergency Med, Saskatoon, SK, Canada. [Thoma, Brent; Chan, Teresa; Lin, Michelle] MedEdLIFE Res Collaborat, San Francisco, CA USA. [Chan, Teresa] McMaster Univ, Dept Med, Div Emergency Med, Hamilton, ON, Canada. [Chan, Teresa] Univ Illinois, Coll Med, Dept Med Educ, Chicago, IL USA. [Desouza, Natalie; Lin, Michelle] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. RP Thoma, B (reprint author), Royal Univ Hosp, EM Residency Training Program, Room 2686,103 Hosp Dr, Saskatoon, SK S7N 0W8, Canada. EM brent.thoma@usask.ca OI Chan, Teresa/0000-0001-6104-462X; Thoma, Brent/0000-0003-1124-5786 NR 6 TC 5 Z9 5 U1 1 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1481-8035 EI 1481-8043 J9 CAN J EMERG MED JI Can. J. Emerg. Med. PD MAR PY 2015 VL 17 IS 2 BP 188 EP 191 DI 10.2310/8000.2014.141393 PG 4 WC Emergency Medicine SC Emergency Medicine GA CE8LY UT WOS:000352095100011 PM 25927262 ER PT J AU Castro, CM Im, H Le, C Lee, H Weissleder, R Birrer, MJ AF Castro, Cesar M. Im, Hyungsoon Le, Christine Lee, Hakho Weissleder, Ralph Birrer, Michael J. TI Exploring alternative ovarian cancer biomarkers using innovative nanotechnology strategies SO CANCER AND METASTASIS REVIEWS LA English DT Review DE Ovarian cancer; Biomarkers; Circulating tumor cells; Ascites; Exosomes; Microfluidics; Nuclearmagnetic resonance; Nanotechnology ID CIRCULATING TUMOR-CELLS; EXOSOMES; RESONANCE AB Our increased understanding of ovarian cancer's blueprints (mediated by DNA and RNA) and behavior (mediated by proteins) points to wide differences across patients that cannot be depicted by histology alone. Conventional diagnosis usually entails an adequate tissue biopsy, which limits serial testing. There is thus a motivation to shift towards easier to obtain clinical samples (e.g., ascites or blood). In response, investigators are increasingly leveraging alternative circulating biomarkers in blood or proximal fluids and harnessing novel profiling platforms to help explore treatment-related effects on such biomarkers in serial fashion. In this review, we discuss how new nanotechnologies we developed intersect with alternative ovarian cancer biomarkers for improved understanding of metastases and therapeutic response. C1 [Castro, Cesar M.; Birrer, Michael J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Castro, Cesar M.; Im, Hyungsoon; Le, Christine; Lee, Hakho; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Castro, CM (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM Castro.Cesar@mgh.harvard.edu; mbirrer@partners.org RI Im, Hyungsoon/A-3178-2009 OI Im, Hyungsoon/0000-0002-0626-1346 FU NCI NIH HHS [R33 CA202064, R01 CA204019] NR 24 TC 1 Z9 1 U1 4 U2 25 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 EI 1573-7233 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD MAR PY 2015 VL 34 IS 1 BP 75 EP 82 DI 10.1007/s10555-014-9546-9 PG 8 WC Oncology SC Oncology GA CE9ZX UT WOS:000352203400007 PM 25543192 ER PT J AU Hammerman, PS Hayes, DN Grandis, JR AF Hammerman, Peter S. Hayes, D. Neil Grandis, Jennifer R. TI Therapeutic Insights from Genomic Studies of Head and Neck Squamous Cell Carcinomas SO CANCER DISCOVERY LA English DT Article ID HUMAN-PAPILLOMAVIRUS; OROPHARYNGEAL CANCER; UNITED-STATES; COPY NUMBER; EXPRESSION; MUTATIONS; RECURRENT; PATHWAY; SUBSET; TUMORS C1 [Hammerman, Peter S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hammerman, Peter S.] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA USA. [Hayes, D. Neil] Univ N Carolina, Lineberger Canc Res Ctr, Dept Hematol Oncol, Chapel Hill, NC 27599 USA. [Grandis, Jennifer R.] Univ Pittsburgh, Dept Otolaryngol, Pittsburgh, PA 15213 USA. [Grandis, Jennifer R.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. [Grandis, Jennifer R.] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA. RP Grandis, JR (reprint author), Univ Pittsburgh, Sch Med, W912 Biomed Sci Tower,Suite 500,200 Lothrop St, Pittsburgh, PA 15213 USA. EM grandisjr@upmc.edu FU NCATS NIH HHS [UL1 TR000005]; NCI NIH HHS [K08 CA163677, P50 CA097190, R01 CA098372]; NIDCR NIH HHS [R01 DE023685] NR 36 TC 10 Z9 10 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD MAR PY 2015 VL 5 IS 3 BP 239 EP 244 DI 10.1158/2159-8290.CD-14-1205 PG 6 WC Oncology SC Oncology GA CF2IV UT WOS:000352371900020 PM 25643909 ER PT J AU Van Rechem, C Black, JC Greninger, P Zhao, Y Donado, C Burrowes, PD Ladd, B Christiani, DC Benes, CH Whetstine, JR AF Van Rechem, Capucine Black, Joshua C. Greninger, Patricia Zhao, Yang Donado, Carlos Burrowes, Paul D. Ladd, Brendon Christiani, David C. Benes, Cyril H. Whetstine, Johnathan R. TI A Coding Single-Nucleotide Polymorphism in Lysine Demethylase KDM4A Associates with Increased Sensitivity to mTOR Inhibitors SO CANCER DISCOVERY LA English DT Article ID CELL LUNG-CANCER; NATURAL-SELECTION; KINASE INHIBITOR; METHYLATION; PATHWAY; SURVIVAL; IMPACT; TARGET; JMJD2A AB SNPs occur within chromatin-modulating factors; however, little is known about how these variants within the coding sequence affect cancer progression or treatment. Therefore, there is a need to establish their biochemical and/or molecular contribution, their use in subclassifying patients, and their impact on therapeutic response. In this report, we demonstrate that coding SNP-A482 within the lysine tridemethylase gene KDM4A/JMJD2A has different allelic frequencies across ethnic populations, associates with differential outcome in patients with non-small cell lung cancer (NSCLC), and promotes KDM4A protein turnover. Using an unbiased drug screen against 87 preclinical and clinical compounds, we demonstrate that homozygous SNP-A482 cells have increased mTOR inhibitor sensitivity. mTOR inhibitors significantly reduce SNP-A482 protein levels, which parallels the increased drug sensitivity observed with KDM4A depletion. Our data emphasize the importance of using variant status as candidate biomarkers and highlight the importance of studying SNPs in chromatin modifiers to achieve better targeted therapy. SIGNIFICANCE: This report documents the first coding SNP within a lysine demethylase that associates with worse outcome in patients with NSCLC. We demonstrate that this coding SNP alters the protein turnover and associates with increased mTOR inhibitor sensitivity, which identifies a candidate biomarker for mTOR inhibitor therapy and a therapeutic target for combination therapy. C1 [Van Rechem, Capucine; Black, Joshua C.; Greninger, Patricia; Donado, Carlos; Burrowes, Paul D.; Ladd, Brendon; Benes, Cyril H.; Whetstine, Johnathan R.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Van Rechem, Capucine; Black, Joshua C.; Greninger, Patricia; Donado, Carlos; Burrowes, Paul D.; Ladd, Brendon; Benes, Cyril H.; Whetstine, Johnathan R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Zhao, Yang; Christiani, David C.] Harvard Univ, Harvard Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Zhao, Yang] Nanjing Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Nanjing, Jiangsu, Peoples R China. [Christiani, David C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA USA. RP Whetstine, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Canc Ctr, Bldg 149,Room 7-213,13th St, Charlestown, MA 02129 USA. EM jwhetstine@hms.harvard.edu RI Black, Joshua/Q-2484-2015 FU American Cancer Society Basic Scholar Grant; MGH Proton Beam Federal Share Grant [CA059267]; NIH [R01GM097360, U54 HG006097]; NIH (NCI) [5R01CA92824]; American Lung Association Lung Cancer Discovery Award; Fund for Medical Discovery; Marsha Rivkin Center for Ovarian Cancer Research; MGH ECOR Tosteson Postdoctoral Fellowship; Jane Coffin Childs Memorial Fund for Medical Research FX The studies conducted in this article were funded by an American Cancer Society Basic Scholar Grant, an MGH Proton Beam Federal Share Grant (CA059267), and NIH R01GM097360 (to J.R. Whetstine); NIH (NCI) grant 5R01CA92824 (to D.C. Christiani); and NIH grant U54 HG006097 (to C.H. Benes). J.R. Whetstine is the Tepper Family MGH Research Scholar and a Leukemia and Lymphoma Society Scholar, as well as a recipient of the American Lung Association Lung Cancer Discovery Award. A postdoctoral fellowship was provided by the Fund for Medical Discovery to C. Van Rechem. C. Van Rechem is the 2014 Skacel Family Marsha Rivkin Center for Ovarian Cancer Research Scholar. This research was supported in part by a grant from the Marsha Rivkin Center for Ovarian Cancer Research. J.C. Black was a fellow of The Jane Coffin Childs Memorial Fund for Medical Research and is supported by an MGH ECOR Tosteson Postdoctoral Fellowship. This investigation has also been aided by a grant from The Jane Coffin Childs Memorial Fund for Medical Research. NR 25 TC 11 Z9 11 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD MAR PY 2015 VL 5 IS 3 BP 245 EP 254 DI 10.1158/2159-8290.CD-14-1159 PG 10 WC Oncology SC Oncology GA CF2IV UT WOS:000352371900021 PM 25564517 ER PT J AU Van Rechem, C Black, JC Boukhali, M Aryee, MJ Graslund, S Haas, W Benes, CH Whetstine, JR AF Van Rechem, Capucine Black, Joshua C. Boukhali, Myriam Aryee, Martin J. Graeslund, Susanne Haas, Wilhelm Benes, Cyril H. Whetstine, Johnathan R. TI Lysine Demethylase KDM4A Associates with Translation Machinery and Regulates Protein Synthesis SO CANCER DISCOVERY LA English DT Article ID MTOR SIGNALING PATHWAY; CANCER-CELLS; METHYLATION; PROLIFERATION; INHIBITORS; IMPACT AB Chromatin-modifying enzymes are predominantly nuclear; however, these factors are also localized to the cytoplasm, and very little is known about their role in this compartment. In this report, we reveal a non-chromatin-linked role for the lysine-specific demethylase KDM4A. We demonstrate that KDM4A interacts with the translation initiation complex and affects the distribution of translation initiation factors within polysome fractions. Furthermore, KDM4A depletion reduced protein synthesis and enhanced the protein synthesis suppression observed with mTOR inhibitors, which paralleled an increased sensitivity to these drugs. Finally, we demonstrate that JIB-04, a JmjC demethylase inhibitor, suppresses translation initiation and enhances mTOR inhibitor sensitivity. These data highlight an unexpected cytoplasmic role for KDM4A in regulating protein synthesis and suggest novel potential therapeutic applications for this class of enzyme. SIGNIFICANCE: This report documents an unexpected cytoplasmic role for the lysine demethylase KDM4A. We demonstrate that KDM4A interacts with the translation initiation machinery, regulates protein synthesis and, upon coinhibition with mTOR inhibitors, enhances the translation suppression and cell sensitivity to these therapeutics. (C) 2015 AACR. C1 [Van Rechem, Capucine; Black, Joshua C.; Boukhali, Myriam; Haas, Wilhelm; Benes, Cyril H.; Whetstine, Johnathan R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Van Rechem, Capucine; Black, Joshua C.; Boukhali, Myriam; Aryee, Martin J.; Haas, Wilhelm; Benes, Cyril H.; Whetstine, Johnathan R.] Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. [Aryee, Martin J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. [Graeslund, Susanne] Univ Toronto, Struct Genom Consortium, Toronto, ON, Canada. RP Whetstine, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Canc Ctr, Bldg 149,Room 7-213,13th St, Charlestown, MA 02129 USA. EM jwhetstine@hms.harvard.edu RI Black, Joshua/Q-2484-2015 FU American Cancer Society Basic Scholar Grant; Massachusetts General Hospital (MGH) Proton Beam Federal Share Grant [CA059267]; NIH [R01GM097360, U54 HG006097]; American Lung Association Lung Cancer Discovery Award; Fund for Medical Discovery; Marsha Rivkin Center for Ovarian Cancer Research FX The studies conducted in this article were funded by the following: the American Cancer Society Basic Scholar Grant, the Massachusetts General Hospital (MGH) Proton Beam Federal Share Grant (CA059267), and NIH R01GM097360 to J.R. Whetstine; and NIH U54 HG006097 to C.H. Benes. J.R. Whetstine is the Tepper Family MGH Research Scholar and a Leukemia and Lymphoma Society Scholar, as well as a recipient of the American Lung Association Lung Cancer Discovery Award. A postdoctoral fellowship was provided by the Fund for Medical Discovery to C. Van Rechem. C. Van Rechem is the 2014 Skacel Family Marsha Rivkin Center for Ovarian Cancer Research Scholar. This research was supported, in part, by a grant from the Marsha Rivkin Center for Ovarian Cancer Research. NR 25 TC 13 Z9 13 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD MAR PY 2015 VL 5 IS 3 BP 255 EP 263 DI 10.1158/2159-8290.CD-14-1326 PG 9 WC Oncology SC Oncology GA CF2IV UT WOS:000352371900022 PM 25564516 ER PT J AU Paraiso, KHT Das Thakur, M Fang, B Koomen, JM Fedorenko, IV John, JK Tsao, H Flaherty, KT Sondak, VK Messina, JL Pasquale, EB Villagra, A Rao, UN Kirkwood, JM Meier, F Sloot, S Gibney, GT Stuart, D Tawbi, H Smalley, KSM AF Paraiso, Kim H. T. Das Thakur, Meghna Fang, Bin Koomen, John M. Fedorenko, Inna V. John, Jobin K. Tsao, Hensin Flaherty, Keith T. Sondak, Vernon K. Messina, Jane L. Pasquale, Elena B. Villagra, Alejandro Rao, Uma N. Kirkwood, John M. Meier, Friedegund Sloot, Sarah Gibney, Geoffrey T. Stuart, Darrin Tawbi, Hussein Smalley, Keiran S. M. TI Ligand-Independent EPHA2 Signaling Drives the Adoption of a Targeted Therapy-Mediated Metastatic Melanoma Phenotype SO CANCER DISCOVERY LA English DT Article ID ACQUIRED-RESISTANCE; MUTANT MELANOMA; MEK INHIBITION; UP-REGULATION; BRAF; PLASTICITY; RECEPTORS; INVASION; VEMURAFENIB; CELLS AB Many patients with BRAF inhibitor resistance can develop disease at new sites, suggesting that drug-induced selection pressure drives metastasis. Here, we used mass spectrometry-based phosphoproteomic screening to uncover ligand-independent EPHA2 signaling as an adaptation to BRAF inhibitor therapy that led to the adoption of a metastatic phenotype. The EPHA2-mediated invasion was AKT-dependent and readily reversible upon removal of the drug as well as through PI3K and AKT inhibition. In xenograft models, BRAF inhibition led to the development of EPHA2-positive metastases. A retrospective analysis of patients with melanoma on BRAF inhibitor therapy showed that 68% of those failing therapy develop metastases at new disease sites, compared with 35% of patients on dacarbazine. Further IHC staining of melanoma specimens taken from patients on BRAF inhibitor therapy as well as metastatic samples taken from patients failing therapy showed increased EPHA2 staining. We suggest that inhibition of ligand-independent EPHA2 signaling may limit metastases associated with BRAF inhibitor therapy. SIGNIFICANCE: This study provides evidence that BRAF inhibition promotes the adoption of a reversible, therapy-driven metastatic phenotype in melanoma. The cotargeting of ligand-independent EPHA2 signaling and BRAF may be one strategy to prevent the development of therapy-mediated disease at new sites. (C) 2014 AACR. C1 [Paraiso, Kim H. T.; Koomen, John M.; John, Jobin K.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Mol Oncol, Tampa, FL 33612 USA. [Das Thakur, Meghna; Stuart, Darrin] Novartis Inst Biomed Res, Emeryville, CA USA. [Fang, Bin] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Prote Core, Tampa, FL 33612 USA. [Fedorenko, Inna V.; Smalley, Keiran S. M.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Tumor Biol, Tampa, FL 33612 USA. [Tsao, Hensin] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sondak, Vernon K.; Messina, Jane L.; Sloot, Sarah; Gibney, Geoffrey T.; Smalley, Keiran S. M.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Cutaneous Oncol, Tampa, FL 33612 USA. [Messina, Jane L.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Anat Pathol, Tampa, FL 33612 USA. [Pasquale, Elena B.] Sanford Burnham Med Res Inst, La Jolla, CA USA. [Villagra, Alejandro] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Immunol, Tampa, FL 33612 USA. [Rao, Uma N.; Kirkwood, John M.; Tawbi, Hussein] Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol,Canc Inst, Pittsburgh, PA 15213 USA. [Meier, Friedegund] Univ Tubingen, Dept Dermatooncol, Tubingen, Germany. RP Smalley, KSM (reprint author), Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM keiran.smalley@moffitt.org RI Fedorenko, Inna/G-9016-2015 OI Fedorenko, Inna/0000-0002-6796-9145 FU NIH [R01 CA161107-01, P50 CA168536-01A1]; Melanoma and Sarcoma Groningen Foundation; Joanna M. Nicolay Melanoma Foundation FX Work in the Smalley laboratory is supported by R01 CA161107-01 and SPORE grant P50 CA168536-01A1 from the NIH. S. Sloot received a grant from the Melanoma and Sarcoma Groningen Foundation. I.V. Fedorenko was supported by the Joanna M. Nicolay Melanoma Foundation. NR 29 TC 20 Z9 20 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD MAR PY 2015 VL 5 IS 3 BP 264 EP 273 DI 10.1158/2159-8290.CD-14-0293 PG 10 WC Oncology SC Oncology GA CF2IV UT WOS:000352371900023 PM 25542447 ER PT J AU Miao, BC Ji, ZY Tan, L Taylor, M Zhang, JM Choi, HG Frederick, DT Kumar, R Wargo, JA Flaherty, KT Gray, NS Tsao, H AF Miao, Benchun Ji, Zhenyu Tan, Li Taylor, Michael Zhang, Jianming Choi, Hwan Geun Frederick, Dennie T. Kumar, Raj Wargo, Jennifer A. Flaherty, Keith T. Gray, Nathanael S. Tsao, Hensin TI EPHA2 Is a Mediator of Vemurafenib Resistance and a Novel Therapeutic Target in Melanoma SO CANCER DISCOVERY LA English DT Article ID RECEPTOR TYROSINE KINASE; BRAF INHIBITOR RESISTANCE; UP-REGULATION; ACQUIRED-RESISTANCE; MUTANT MELANOMA; MAPK PATHWAY; CANCER; EXPRESSION; ACTIVATION; MUTATIONS AB BRAF V600E is the most common oncogenic lesion in melanoma and results in constitutive activation of the MAPK pathway and uncontrolled cell growth. Selective BRAF inhibitors such as vemurafenib have been shown to neutralize oncogenic signaling, restrain cellular growth, and improve patient outcome. Although several mechanisms of vemurafenib resistance have been described, directed solutions to overcome these resistance lesions are still lacking. Herein, we found that vemurafenib resistance can be (i) mediated by EPHA2, a member of the largest receptor tyrosine kinases (RTK) subfamily erythropoietin-producing hepatocellular (EPH) receptors, and (ii) associated with a greater phenotypic dependence on EPHA2. Furthermore, we developed a series of first-in-class EPHA2 inhibitors and show that these new compounds potently induce apoptosis, suppress viability, and abrogate tumorigenic growth of melanoma cells, including those that are resistant to vemurafenib. These results provide proof of concept that RTK-guided growth, and therapeutic resistance, can be prospectively defined and selectively targeted. SIGNIFICANCE: In this study, we show that resistance to selective BRAF inhibitors can be mediated by the RTK EPHA2. Furthermore, direct targeting of EPHA2 can successfully suppress melanoma growth and mitigate therapeutic resistance. C1 [Miao, Benchun; Ji, Zhenyu; Taylor, Michael; Kumar, Raj; Tsao, Hensin] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Miao, Benchun; Ji, Zhenyu; Kumar, Raj; Tsao, Hensin] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Tan, Li; Zhang, Jianming; Choi, Hwan Geun; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Tan, Li; Choi, Hwan Geun; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Frederick, Dennie T.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Wargo, Jennifer A.] Univ Texas MD Anderson Canc Ctr, Div Surg, Dept Surg Oncol, Houston, TX 77030 USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. [Flaherty, Keith T.; Tsao, Hensin] Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Edwards 211,55 Fruit St, Boston, MA 02114 USA. EM htsao@partners.org FU NIH [K24 CA149202, P01CA163222, 5T32AR007098, 5T32CA071345, R01 CA173469]; American Skin Association FX This work was supported in part by the NIH (K24 CA149202 to H. Tsao; P01CA163222 to H. Tsao, K.T. Flaherty, and D.T. Frederick; 5T32AR007098 to B. Miao; 5T32CA071345 to Z.Ji; and R01 CA173469 to N.S. Gray), the American Skin Association (to H. Tsao), and the generous donors to the MGH Millennium Melanoma Fund (to H. Tsao). NR 44 TC 20 Z9 20 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD MAR PY 2015 VL 5 IS 3 BP 274 EP 287 DI 10.1158/2159-8290.CD-14-0295 PG 14 WC Oncology SC Oncology GA CF2IV UT WOS:000352371900024 PM 25542448 ER PT J AU Kleppe, M Kwak, M Koppikar, P Riester, M Keller, M Bastian, L Hricik, T Bhagwat, N McKenney, AS Papalexi, E Abdel-Wahab, O Rampal, R Marubayashi, S Chen, JJ Romanet, V Fridman, JS Bromberg, J Teruya-Feldstein, J Murakami, M Radimerski, T Michor, F Fan, R Levine, RL AF Kleppe, Maria Kwak, Minsuk Koppikar, Priya Riester, Markus Keller, Matthew Bastian, Lennart Hricik, Todd Bhagwat, Neha McKenney, Anna Sophia Papalexi, Efthymia Abdel-Wahab, Omar Rampal, Raajit Marubayashi, Sachie Chen, Jonathan J. Romanet, Vincent Fridman, Jordan S. Bromberg, Jacqueline Teruya-Feldstein, Julie Murakami, Masato Radimerski, Thomas Michor, Franziska Fan, Rong Levine, Ross L. TI JAK-STAT Pathway Activation in Malignant and Nonmalignant Cells Contributes to MPN Pathogenesis and Therapeutic Response SO CANCER DISCOVERY LA English DT Article ID TYROSINE KINASE JAK2; MYELOPROLIFERATIVE NEOPLASMS; HEMATOPOIETIC STEM; POLYCYTHEMIA-VERA; MYELOID METAPLASIA; PROGENITOR CELLS; MUTATION; MYELOFIBROSIS; INHIBITOR; INCB018424 AB The identification of JAK2/MPL mutations in patients with myeloproliferative neoplasms (MPN) has led to the clinical development of JAK kinase inhibitors, including ruxolitinib. Ruxolitinib reduces splenomegaly and systemic symptoms in myelofibrosis and improves overall survival; however, the mechanism by which JAK inhibitors achieve efficacy has not been delineated. Patients with MPN present with increased levels of circulating proinflammatory cytokines, which are mitigated by JAK inhibitor therapy. We sought to elucidate mechanisms by which JAK inhibitors attenuate cytokine-mediated pathophysiology. Single-cell profiling demonstrated that hematopoietic cells from myelofibrosis models and patient samples aberrantly secrete inflammatory cytokines. Panhematopoietic Stat3 deletion reduced disease severity and attenuated cytokine secretion, with similar efficacy as observed with ruxolitinib therapy. In contrast, Stat3 deletion restricted to MPN cells did not reduce disease severity or cytokine production. Consistent with these observations, we found that malignant and nonmalignant cells aberrantly secrete cytokines and JAK inhibition reduces cytokine production from both populations. SIGNIFICANCE: Our results demonstrate that JAK-STAT3-mediated cytokine production from malignant and nonmalignant cells contributes to MPN pathogenesis and that JAK inhibition in both populations is required for therapeutic effi cacy. These findings provide novel insight into the mechanisms by which JAK kinase inhibition achieves therapeutic effi cacy in MPNs. (C) 2015 AACR. C1 [Kleppe, Maria; Koppikar, Priya; Keller, Matthew; Bastian, Lennart; Hricik, Todd; Bhagwat, Neha; McKenney, Anna Sophia; Papalexi, Efthymia; Abdel-Wahab, Omar; Rampal, Raajit; Marubayashi, Sachie; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Kwak, Minsuk; Chen, Jonathan J.; Fan, Rong] Yale Univ, Dept Biomed Engn, New Haven, CT USA. [Riester, Markus; Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Riester, Markus; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Bhagwat, Neha; McKenney, Anna Sophia] Gerstner Sloan Kettering Grad Sch Biomed Sci, New York, NY USA. [McKenney, Anna Sophia] Weill Cornell Rockefeller Sloan Kettering Triinst, New York, NY USA. [Abdel-Wahab, Omar; Rampal, Raajit] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10065 USA. [Romanet, Vincent; Murakami, Masato; Radimerski, Thomas] Novartis Inst BioMed Res, Dis Area Oncol, Basel, Switzerland. [Fridman, Jordan S.] Incyte Corp, Wilmington, DE USA. [Bromberg, Jacqueline] Mem Sloan Kettering Canc Ctr, Dept Med, Breast Canc Serv, New York, NY 10065 USA. [Teruya-Feldstein, Julie] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Fan, Rong] Yale Comprehens Canc Ctr, New Haven, CT USA. RP Levine, RL (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Human Oncol & Pathogenesis Program, Leukemia Serv, 415 East 68th St,1275 York Ave,Box 20, New York, NY 10065 USA. EM rong.fan@yale.edu; leviner@mskcc.org OI Abdel-Wahab, Omar/0000-0002-3907-6171 FU Dana-Farber Cancer Institute's Physical Sciences Oncology Center [U54CA143798-01]; NCI [1R01CA151949-01, 1R01CA138234-01]; NIDDK [1U01DK104331-01]; EMBO Long-Term Fellowship; National Institute of General Medical Sciences of the NIH [T32GM007739] FX This work was supported by the Dana-Farber Cancer Institute's Physical Sciences Oncology Center (U54CA143798-01), to R.L. Levine, R. Fan, M. Riester, and F. Michor; NCI 1R01CA151949-01 to R.L. Levine; and NCI 1R01CA138234-01 to F. Michor and R.L. Levine, and partly by NIDDK 1U01DK104331-01 to R. Fan and R.L. Levine. M. Kleppe is a fellow of the Leukemia and Lymphoma Society and was previously supported by an EMBO Long-Term Fellowship. A.S. McKenney was supported by a Medical Scientist Training Program grant from the National Institute of General Medical Sciences of the NIH under award number T32GM007739 to the Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program. NR 34 TC 32 Z9 32 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD MAR PY 2015 VL 5 IS 3 BP 316 EP 331 DI 10.1158/2159-8290.CD-14-0736 PG 16 WC Oncology SC Oncology GA CF2IV UT WOS:000352371900027 PM 25572172 ER PT J AU Sabado, RL Pavlick, A Gnjatic, S Cruz, CM Vengco, I Hasan, F Spadaccia, M Darvishian, F Chiriboga, L Holman, RM Escalon, J Muren, C Escano, C Yepes, E Sharpe, D Vasilakos, JP Rolnitzsky, L Goldberg, JD Mandeli, J Adams, S Jungbluth, A Pan, L Venhaus, R Ott, PA Bhardwaj, N AF Sabado, Rachel Lubong Pavlick, Anna Gnjatic, Sacha Cruz, Crystal M. Vengco, Isabelita Hasan, Farah Spadaccia, Meredith Darvishian, Farbod Chiriboga, Luis Holman, Rose Marie Escalon, Juliet Muren, Caroline Escano, Crystal Yepes, Ethel Sharpe, Dunbar Vasilakos, John P. Rolnitzsky, Linda Goldberg, Judith D. Mandeli, John Adams, Sylvia Jungbluth, Achim Pan, Linda Venhaus, Ralph Ott, Patrick A. Bhardwaj, Nina TI Resiquimod as an Immunologic Adjuvant for NY-ESO-1 Protein Vaccination in Patients with High-Risk Melanoma SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID REGULATORY T-CELLS; IMMUNE-RESPONSES; PEPTIDE VACCINE; RECEPTOR AGONISTS; CLINICAL BENEFIT; DENDRITIC CELLS; CANCER-PATIENTS; TLR7 AGONIST; ANTIGEN; INDUCTION AB The Toll-like receptor (TLR) 7/8 agonist resiquimod has been used as an immune adjuvant in cancer vaccines. We evaluated the safety and immunogenicity of the cancer testis antigen NY-ESO-1 given in combination with Montanide (Seppic) with or without resiquimod in patients with high-risk melanoma. In part I of the study, patients received 100 mu g of full-length NY-ESO-1 protein emulsified in 1.25 mL of Montanide (day 1) followed by topical application of 1,000 mg of 0.2% resiquimod gel on days 1 and 3 (cohort 1) versus days 1, 3, and 5 (cohort 2) of a 21-day cycle. In part II, patients were randomized to receive 100-mu g NY-ESO-1 protein plus Montanide (day 1) followed by topical application of placebo gel [(arm A; n = 8) or 1,000 mg of 0.2% resiquimod gel (arm B; n = 12)] using the dosing regimen established in part I. The vaccine regimens were generally well tolerated. NY-ESO-1-specific humoral responses were induced or boosted in all patients, many of whom had high titer antibodies. In part II, 16 of 20 patients in both arms had NY-ESO-1-specific CD4(+) T-cell responses. CD8(+) T-cell responses were only seen in 3 of 12 patients in arm B. Patients with TLR7 SNP rs179008 had a greater likelihood of developing NY-ESO-1-specific CD8(+) responses. In conclusion, NY-ESO-1 protein in combination with Montanide with or without topical resiquimod is safe and induces both antibody and CD4(+) T-cell responses in the majority of patients; the small proportion of CD8(+) T-cell responses suggests that the addition of topical resiquimod to Montanide is not sufficient to induce consistent NY-ESO-1-specific CD8(+) T-cell responses. (C) 2015 AACR. C1 [Sabado, Rachel Lubong; Pavlick, Anna; Cruz, Crystal M.; Vengco, Isabelita; Hasan, Farah; Spadaccia, Meredith; Holman, Rose Marie; Escalon, Juliet; Muren, Caroline; Escano, Crystal; Yepes, Ethel; Sharpe, Dunbar; Adams, Sylvia; Ott, Patrick A.; Bhardwaj, Nina] NYU, Sch Med, Inst Canc, New York, NY USA. [Sabado, Rachel Lubong; Gnjatic, Sacha; Mandeli, John; Bhardwaj, Nina] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Boston, MA USA. [Gnjatic, Sacha; Pan, Linda; Venhaus, Ralph] Ludwig Inst Canc Res, Boston, MA USA. [Darvishian, Farbod; Chiriboga, Luis; Bhardwaj, Nina] Icahn Sch Med Mt Sinai, Dept Pathol, New York, NY 10029 USA. [Vasilakos, John P.] 3M Drug Delivery Syst Div, Boston, MA USA. [Rolnitzsky, Linda; Goldberg, Judith D.] NYU, Sch Med, Div Biostat, New York, NY USA. [Jungbluth, Achim] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Ott, Patrick A.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bhardwaj, N (reprint author), Icahn Sch Med Mt Sinai, Hess Ctr Sci & Med, Tisch Canc Inst, 1470 Madison Ave,5-116, New York, NY 10029 USA. EM Nina.Bhardwaj@mssm.edu OI Hasan, Farah/0000-0001-6941-7822; Chiriboga, Luis/0000-0002-2028-6873; Goldberg, Judith D./0000-0003-3758-6976 FU Ludwig Institute for Cancer Research; Cancer Research Institute, Cancer Vaccine Collaborative; Cancer Vaccine Collaborative for Immunological Monitoring; New York University Cancer Center Support Grant [5 P30 CA16087] FX This study was sponsored and funded by the Ludwig Institute for Cancer Research with a supplemental grant from the Cancer Research Institute as part of the Cancer Vaccine Collaborative. S. Gnjatic was supported by a grant from the Cancer Vaccine Collaborative for Immunological Monitoring. J.D. Goldberg and L. Rolnitzky were supported by 5 P30 CA16087 New York University Cancer Center Support Grant 5 P30 CA16087. NR 46 TC 12 Z9 13 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD MAR PY 2015 VL 3 IS 3 BP 278 EP 287 DI 10.1158/2326-6066.CIR-14-0202 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA CF2LP UT WOS:000352379100007 PM 25633712 ER PT J AU Johnson, DB Lovly, CM Flavin, M Panageas, KS Ayers, GD Zhao, ZG Iams, WT Colgan, M DeNoble, S Terry, CR Berry, EG Iafrate, AJ Sullivan, RJ Carvajal, RD Sosman, JA AF Johnson, Douglas B. Lovly, Christine M. Flavin, Marisa Panageas, Katherine S. Ayers, Gregory D. Zhao, Zhiguo Iams, Wade T. Colgan, Marta DeNoble, Sarah Terry, Charles R. Berry, Elizabeth G. Iafrate, A. John Sullivan, Ryan J. Carvajal, Richard D. Sosman, Jeffrey A. TI Impact of NRAS Mutations for Patients with Advanced Melanoma Treated with Immune Therapies SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID METASTATIC MELANOMA; CLINICAL-RESPONSE; IPILIMUMAB; EXPRESSION; SAFETY; CARCINOMA; NIVOLUMAB; ANTI-PD-1; CANCER; B7-H1 AB Activating NRAS mutations are found in 15% to 20% of melanomas. Immune therapies have become a mainstay in advanced melanoma treatment. We sought to evaluate whether tumor genotype (e.g., NRAS mutations) correlates with benefit from immune therapy in melanoma. We identified 229 patients with melanoma treated with immune therapies [IL2, ipilimumab, or anti-programmed cell death-1/ligand-1 (PD-1/PD-L1)] at three centers and compared clinical outcomes following immune therapy for patients with or without NRAS mutations. Of the 229 patients with melanoma, 60 had NRAS mutation, 53 had BRAF mutation, and 116 had NRAS/BRAF wild type. The NRAS-mutant cohort had superior or a trend to superior outcomes compared with the other cohorts in terms of response to first-line immune therapy (28% vs. 16%, P = 0.04), response to any line of immune therapy (32% vs. 20%, P = 0.07), clinical benefit (response + stable disease lasting >= 24 weeks; 50% vs. 31%, P < 0.01), and progression-free survival (median, 4.1 vs. 2.9 months, P = 0.09). Benefit from anti-PD-1/PD-L1 was particularly marked in the NRAS cohort (clinical benefit rate 73% vs. 35%). In an independent group of patient samples, NRAS-mutant melanoma had higher PD-L1 expression (although not statistically significant) compared with other genotypes (8/12 vs. 9/20 samples with >= 1% expression; 6/12 vs. 6/20 samples with >= 5% expression), suggesting a potential mechanism for the clinical results. This retrospective study suggests that NRAS mutations in advanced melanoma correlate with increased benefit from immune-based therapies compared with other genetic subtypes. If confirmed by prospective studies, this may be explained in part by high rates of PD-L1 expression. (C) 2015 AACR. C1 [Johnson, Douglas B.; Lovly, Christine M.; Iams, Wade T.; Terry, Charles R.; Berry, Elizabeth G.; Sosman, Jeffrey A.] Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA. [Johnson, Douglas B.; Lovly, Christine M.; Iams, Wade T.; Terry, Charles R.; Berry, Elizabeth G.; Sosman, Jeffrey A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Flavin, Marisa; Panageas, Katherine S.; Colgan, Marta] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Ayers, Gregory D.; Zhao, Zhiguo] Vanderbilt Univ, Sch Med, Ctr Quantitat Sci, Nashville, TN 37212 USA. [DeNoble, Sarah; Iafrate, A. John; Sullivan, Ryan J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Carvajal, Richard D.] Columbia Univ, Med Ctr, New York, NY USA. RP Johnson, DB (reprint author), Vanderbilt Univ, Med Ctr, 777 Preston Res Bldg, Nashville, TN 37232 USA. EM douglas.b.johnson@vanderbilt.edu FU NIH [K12 CA0906525, K24]; Damon Runyon Clinical Investigator Award; American Cancer Society Professorship; Ingram Professorship; CTSA from the National Center for Advancing Translational Sciences [UL1TR000445]; Anbinder Fund FX This study was supported by NIH K12 CA0906525 (to D.B. Johnson and C.M Lovly) and a Damon Runyon Clinical Investigator Award. J.A. Sosman was supported by an NIH K24 grant, an American Cancer Society Professorship, and an Ingram Professorship. The project described was supported by CTSA award no. UL1TR000445 from the National Center for Advancing Translational Sciences. The MSKCC Sequenom facility was supported by the Anbinder Fund. NR 34 TC 25 Z9 25 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD MAR PY 2015 VL 3 IS 3 BP 288 EP 295 DI 10.1158/2326-6066.CIR-14-0207 PG 8 WC Oncology; Immunology SC Oncology; Immunology GA CF2LP UT WOS:000352379100008 PM 25736262 ER PT J AU Dhakal, BP Malhotra, R Murphy, RM Pappagianopoulos, PP Baggish, AL Weiner, RB Houstis, NE Eisman, AS Hough, SS Lewis, GD AF Dhakal, Bishnu P. Malhotra, Rajeev Murphy, Ryan M. Pappagianopoulos, Paul P. Baggish, Aaron L. Weiner, Rory B. Houstis, Nicholas E. Eisman, Aaron S. Hough, Stacyann S. Lewis, Gregory D. TI Mechanisms of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction The Role of Abnormal Peripheral Oxygen Extraction SO CIRCULATION-HEART FAILURE LA English DT Article DE diastole; exercise; heart failure ID MAXIMAL UPRIGHT EXERCISE; SKELETAL-MUSCLE; CHRONOTROPIC INCOMPETENCE; CARDIAC-OUTPUT; OLDER PATIENTS; STROKE VOLUME; RATE RESPONSE; BLOOD-FLOW; CAPACITY; TRIAL AB Background-Exercise capacity as measured by peak oxygen uptake (Vo(2)) is similarly impaired in patients with heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). However, characterization of how each component of Vo(2) changes in response to incremental exercise in HFpEF versus HFrEF has not been previously defined. We hypothesized that abnormally low peripheral o(2) extraction (arterio-mixed venous o(2) content difference, [C(a-v)o(2)]) during exercise significantly contributes to impaired exercise capacity in HFpEF. Methods and Results-We performed maximum incremental cardiopulmonary exercise testing with invasive hemodynamic monitoring on 104 patients with symptomatic NYHA II to IV heart failure (HFpEF, n=48, peak Vo(2)=13.9 +/- 0.5 mL kg(-1) min(-1), mean +/- SEM, and HFrEF, n= 56, peak Vo(2) = 12.1 +/- 0.5 mL kg(-1) min(-1)) and 24 control subjects (peak Vo(2) 27.0 +/- 1.7 mL kg(-1) min(-1)). Peak exercise C(a-v)o(2) was lower in HFpEF compared with HFrEF (11.5 +/- 0.27 versus 13.5 +/- 0.34 mL/dL, respectively, P<0.0001), despite no differences in age, hemoglobin level, peak respiratory exchange ratio, Cao(2), or cardiac filling pressures. Peak C(a-v)o(2) and peak heart rate emerged as the leading predictors of peak Vo(2) in HFpEF. Impaired peripheral o(2) extraction was the predominant limiting factor to exercise capacity in 40% of patients with HFpEF and was closely related to elevated systemic blood pressure during exercise (r=0.49, P=0.0005). Conclusions-In the first study to directly measure C(a-v)o(2) throughout exercise in HFpEF, HFrEF, and normals, we found that peak C(a-v)o(2) was a major determinant of exercise capacity in HFpEF. The important functional limitation imposed by impaired o(2) extraction may reflect intrinsic abnormalities in skeletal muscle or peripheral microvascular function, and represents a potential target for therapeutic intervention. C1 [Dhakal, Bishnu P.; Malhotra, Rajeev; Murphy, Ryan M.; Baggish, Aaron L.; Weiner, Rory B.; Houstis, Nicholas E.; Eisman, Aaron S.; Lewis, Gregory D.] Harvard Univ, Sch Med, Dept Med, Div Cardiol,Massachusetts Gen Hosp, Boston, MA USA. [Pappagianopoulos, Paul P.; Hough, Stacyann S.; Lewis, Gregory D.] Harvard Univ, Sch Med, Dept Med, Pulm & Crit Care Unit,Massachusetts Gen Hosp, Boston, MA USA. RP Lewis, GD (reprint author), Massachusetts Gen Hosp, Heart Failure & Cardiac Transplantat Unit, Bigelow 800,55 Fruit St, Boston, MA 02114 USA. EM glewis@partners.org OI Malhotra, Rajeev/0000-0003-0120-4630 FU Hassenfeld Clinical Scholars Program; Massachusetts General Hospital Cardiac Performance Program; [K23 HL091106]; [R01 HL119154] FX This work was supported by K23 HL091106, R01 HL119154, the Hassenfeld Clinical Scholars Program (Dr Lewis and A.S. Eisman), and the Massachusetts General Hospital Cardiac Performance Program (Drs Baggish, Weiner, and Lewis) NR 60 TC 50 Z9 50 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAR PY 2015 VL 8 IS 2 BP 286 EP + DI 10.1161/CIRCHEARTFAILURE.114.001825 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CF0JL UT WOS:000352229500009 PM 25344549 ER PT J AU Nathan, AS Loukas, B Moko, L Wu, F Rhodes, J Rathod, RH Systrom, DM Tikkanen, AU Shafer, K Lewis, GD Landzberg, MJ Opotowsky, AR AF Nathan, Ashwin S. Loukas, Brittani Moko, Lilamarie Wu, Fred Rhodes, Jonathan Rathod, Rahul H. Systrom, David M. Tikkanen, Ana Ubeda Shafer, Keri Lewis, Gregory D. Landzberg, Michael J. Opotowsky, Alexander R. TI Exercise Oscillatory Ventilation in Patients With Fontan Physiology SO CIRCULATION-HEART FAILURE LA English DT Article DE cardiopulmonary exercise test; Cheyne-Stokes respiration; exercise; Fontan procedure; heart defects, congenital; ventilation ID CHRONIC HEART-FAILURE; AMBULATORY PATIENTS; CARDIAC TRANSPLANTATION; RISK STRATIFICATION; OXYGEN-CONSUMPTION; AEROBIC CAPACITY; PROGNOSTIC VALUE; MORTALITY; ADULTS; CHILDREN AB Background-Exercise oscillatory ventilation (EOV) refers to regular oscillations in minute ventilation (V-E) during exercise. Its presence correlates with heart failure severity and worse prognosis in adults with acquired heart failure. We evaluated the prevalence and predictive value of EOV in patients with single ventricle Fontan physiology. Methods and Results-We performed a cross-sectional analysis and prospective survival analysis of patients who had undergone a Fontan procedure and subsequent cardiopulmonary exercise test. Data were reviewed for baseline characteristics and incident mortality, heart transplant, or nonelective cardiovascular hospitalization. EOV was defined as regular oscillations for >60% of exercise duration with amplitude > 15% of average V-E. Survival analysis was performed using Cox regression. Among 253 subjects, EOV was present in 37.5%. Patients with EOV were younger (18.8 +/- 9.0 versus 21.7 +/- 10.1 years; P=0.02). EOV was associated with higher New York Heart Association functional class (P=0.02) and V-E/V-CO2 slope (36.8 +/- 6.9 versus 33.7 +/- 5.7; P=0.0002), but not with peak Vo(2) (59.7 +/- 14.3 versus 61.0 +/- 16.0% predicted; P=0.52) or noninvasive measures of cardiac function. The presence of EOV was associated with slightly lower mean cardiac index but other invasive hemodynamic variables were similar. During a median follow-up of 5.5 years, 22 patients underwent transplant or died (n=19 primary deaths, 3 transplants with 2 subsequent deaths). EOV was associated with increased risk of death or transplant (hazard ratio, 3.9; 95% confidence interval, 1.5-10.0; P=0.002) and also predicted the combined outcome of death, transplant, or nonelective cardiovascular hospitalization after adjusting for New York Heart Association functional class, peak Vo(2), and other covariates (multivariable hazard ratio, 2.0; 95% confidence interval, 1.2-3.6; P=0.01). Conclusions-EOV is common in the Fontan population and strongly predicts lower transplant-free survival. C1 [Nathan, Ashwin S.; Wu, Fred; Systrom, David M.; Shafer, Keri; Landzberg, Michael J.; Opotowsky, Alexander R.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Loukas, Brittani; Moko, Lilamarie; Wu, Fred; Rhodes, Jonathan; Rathod, Rahul H.; Tikkanen, Ana Ubeda; Shafer, Keri; Landzberg, Michael J.; Opotowsky, Alexander R.] Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Tikkanen, Ana Ubeda] Boston Childrens Hosp, Dept Cardiovasc Surg, Boston, MA 02115 USA. [Lewis, Gregory D.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Opotowsky, AR (reprint author), Boston Childrens Hosp, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA. EM alexander.opotowsky@cardio.chboston.org FU National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288]; Dunlevie Family Fund FX This work was supported by U01 grants from the National Heart, Lung, and Blood Institute (HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, and HL068288). The contents are solely the responsibility of the authors and do not necessarily represent the official views of National Heart, Lung, and Blood Institute or National Institutes of Health. Drs Opotowsky, Shafer, Landzberg, and Wu were supported by the Dunlevie Family Fund. NR 45 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAR PY 2015 VL 8 IS 2 BP 304 EP 311 DI 10.1161/CIRCHEARTFAILURE.114.001749 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CF0JL UT WOS:000352229500011 PM 25550441 ER PT J AU Teicher, BA Anderson, KC AF Teicher, Beverly A. Anderson, Kenneth C. TI CCR 20th Anniversary Commentary: In the Beginning, There Was PS-341 SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID PROTEASOME INHIBITOR PS-341; HEMATOLOGIC MALIGNANCIES; KAPPA-B; MYELOMA; ACTIVATION; MLN9708; CELLS AB Proteasome inhibitors have a 20-year history in cancer therapy. The first proteasome inhibitor, bortezomib, a breakthrough treatment for multiple myeloma, moved rapidly through development from the bench in 1994 to first FDA approval in 2003. Clinical Cancer Research has chronicled the development of proteasome inhibitors with publication of reports on bortezo (MLN9708). (C) 2015 AACR. C1 [Teicher, Beverly A.] NCI, Div Canc Treatment & Diag, Rockville, MD USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Teicher, BA (reprint author), NCI, NIH, 9609 Med Ctr Dr,RM 4-W602,MSC 9735, Bethesda, MD 20892 USA. EM Beverly.Teicher@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 11 TC 6 Z9 6 U1 0 U2 1 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 MAR PY 2015 VL 21 IS 5 BP 939 EP 941 DI 10.1158/1078-0432.CCR-14-2549 PG 3 WC Oncology SC Oncology GA CE6XZ UT WOS:000351982800001 PM 25733705 ER PT J AU Goldman, J Eckhardt, SG Borad, MJ Curtis, KK Hidalgo, M Calvo, E Ryan, DP Wirth, LJ Parikh, A Partyka, J Faessel, H Gangolli, E Stewart, S Rosen, LS Bowles, DW AF Goldman, Jonathan Eckhardt, S. Gail Borad, Mitesh J. Curtis, Kelly K. Hidalgo, Manuel Calvo, Emiliano Ryan, David P. Wirth, Lori J. Parikh, Asit Partyka, James Faessel, Helene Gangolli, Esha Stewart, Sally Rosen, Lee S. Bowles, Daniel W. TI Phase I Dose-Escalation Trial of the Oral Investigational Hedgehog Signaling Pathway Inhibitor TAK-441 in Patients with Advanced Solid Tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID BASAL-CELL CARCINOMAS; SONIC HEDGEHOG; HUMAN HOMOLOG; CANCER; MUTATIONS; EFFICACY; RECEPTOR; MODEL; PTCH AB Purpose: This first-in-human study assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of single and multiple doses of TAK-441, an investigational inhibitor of the Hedgehog signaling pathway. Experimental Design: Patients with advanced, solid tumors received daily oral TAK-441 (50-1,600 mg/day); daily dose was doubled in each subsequent cohort until the maximum tolerated/ feasible dose (MTD/MFD) was reached. Blood was collected to evaluate TAK-441 plasma concentrations. Skin biopsies were obtained to evaluate suppression of the Hedgehog-regulated gene Gli1. Results: Thirty-four patients were enrolled (median age 59). The most common diagnoses were colorectal cancer (26%), basal cell carcinoma (BCC, 21%), and pancreatic cancer (9%). The MFD of 1,600 mg/day (based on tablet size and strength) was considered the MTD. Dose-limiting toxicities included muscle spasms and fatigue. Grade >= 3 treatment-emergent adverse events, regardless of causality, occurred in 15 patients (44%), of which hyponatremia (n = 4) and fatigue (n = 3) were most common. Oral absorption was fairly rapid; median T-max was 2.0 to 4.0 hours after a single dose. Mean elimination half-life was 13.5 to 22.6 hours. Systemic exposure of TAK-441 based on the area under the plasma concentrationtime curve was linear across the dose range. Gli1 expression in skin biopsies was strongly inhibited at all dose levels. Best response was partial response (1 patient with BCC) and stable disease (7 patients with various solid tumors). Conclusions: TAK-441 was generally well tolerated up to MFD of 1,600 mg/day, with preliminary antitumor activity. Further study of TAK-441 may be appropriate in populations selected for tumors with ligand-dependent or independent Hedgehog signaling. C1 [Goldman, Jonathan; Stewart, Sally; Rosen, Lee S.] UCLA Hematol & Oncol, Santa Monica, CA 90404 USA. [Eckhardt, S. Gail; Bowles, Daniel W.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Borad, Mitesh J.; Curtis, Kelly K.] Mayo Clin, Scottsdale, AZ USA. [Hidalgo, Manuel; Calvo, Emiliano] START Madrid, Ctr Integral Oncol Clara Campal, Madrid, Spain. [Ryan, David P.; Wirth, Lori J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Parikh, Asit] Takeda Pharmaceut Int Co, Deerfield, IL USA. [Partyka, James; Faessel, Helene; Gangolli, Esha] Takeda Pharmaceut Int Co, Cambridge, MA USA. RP Goldman, J (reprint author), UCLA Hematol & Oncol, Drug Dev, Clin Trials Thorac Oncol, 2020 Santa Monica Blvd,Suite 600, Santa Monica, CA 90404 USA. EM JWGoldman@mednet.ucla.edu RI HIDALGO, MANUEL/I-4995-2015 OI HIDALGO, MANUEL/0000-0002-3765-3318 FU Takeda Pharmaceuticals International Co. FX Financial support for the conduct of this study was provided by Takeda Pharmaceuticals International Co. and financial support for medical writing and editorial assistance was provided by Millennium: The Takeda Oncology Company. NR 29 TC 7 Z9 7 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 2015 VL 21 IS 5 BP 1002 EP 1009 DI 10.1158/1078-0432.CCR-14-1234 PG 8 WC Oncology SC Oncology GA CE6XZ UT WOS:000351982800012 PM 25501576 ER PT J AU Piesche, M Ho, VT Kim, H Nakazaki, Y Nehil, M Yaghi, NK Kolodin, D Weiser, J Altevogt, P Kiefel, H Alyea, EP Antin, JH Cutler, C Koreth, J Canning, C Ritz, J Soiffer, RJ Dranoff, G AF Piesche, Matthias Ho, Vincent T. Kim, Haesook Nakazaki, Yukoh Nehil, Michael Yaghi, Nasser K. Kolodin, Dmitriy Weiser, Jeremy Altevogt, Peter Kiefel, Helena Alyea, Edwin P. Antin, Joseph H. Cutler, Corey Koreth, John Canning, Christine Ritz, Jerome Soiffer, Robert J. Dranoff, Glenn TI Angiogenic Cytokines Are Antibody Targets During Graft-versus-Leukemia Reactions SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; STEM-CELL TRANSPLANTATION; MEDIATED TUMOR DESTRUCTION; BONE-MARROW-TRANSPLANTATION; CD8(+) T-CELLS; ADHESION MOLECULE; CANCER; RESPONSES; IMMUNITY; THERAPY AB Purpose: The graft-versus-leukemia (GVL) reaction is an important example of immune-mediated tumor destruction. A coordinated humoral and cellular response accomplishes leukemia cell killing, but the specific targets remain largely uncharacterized. To learn more about the antigens that elicit antibodies during GVL reactions, we analyzed patients with advanced myelodysplasia (MDS) and acute myelogenous leukemia (AML) who received an autologous, granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor cell vaccine early after allogeneic hematopoietic stem cell transplantation (HSCT). Experimental Design: A combination of tumor-derived cDNA expression library screening, protein microarrays, and antigen-specific ELISAs were used to characterize sera obtained longitudinally from 15 patients with AML/MDS who were vaccinated early after allogeneic HSCT. Results: A broad, therapy-induced antibody response was uncovered, which primarily targeted intracellular proteins that function in growth, transcription/translation, metabolism, and homeostasis. Unexpectedly, antibodies were also elicited against eight secreted angiogenic cytokines that play critical roles in leukemogenesis. Antibodies to the angiogenic cytokines were evident early after therapy, and in some patients manifested a diversification in reactivity over time. Patients that developed antibodies to multiple angiogenic cytokines showed prolonged remission and survival. Conclusions: These results reveal a potent humoral response during GVL reactions induced with vaccination early after allogeneic HSCT and raise the possibility that antibodies, in conjunction with natural killer cells and T lymphocytes, may contribute to immune-mediated control of myeloid leukemias. C1 [Piesche, Matthias; Ho, Vincent T.; Nakazaki, Yukoh; Nehil, Michael; Yaghi, Nasser K.; Weiser, Jeremy; Alyea, Edwin P.; Antin, Joseph H.; Cutler, Corey; Koreth, John; Canning, Christine; Ritz, Jerome; Soiffer, Robert J.; Dranoff, Glenn] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Piesche, Matthias; Ho, Vincent T.; Nakazaki, Yukoh; Nehil, Michael; Yaghi, Nasser K.; Weiser, Jeremy; Alyea, Edwin P.; Antin, Joseph H.; Cutler, Corey; Koreth, John; Canning, Christine; Ritz, Jerome; Soiffer, Robert J.; Dranoff, Glenn] Brigham & Womens Hosp, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Piesche, Matthias; Ho, Vincent T.; Nakazaki, Yukoh; Nehil, Michael; Yaghi, Nasser K.; Weiser, Jeremy; Alyea, Edwin P.; Antin, Joseph H.; Cutler, Corey; Koreth, John; Canning, Christine; Ritz, Jerome; Soiffer, Robert J.; Dranoff, Glenn] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Piesche, Matthias; Ho, Vincent T.; Nakazaki, Yukoh; Nehil, Michael; Yaghi, Nasser K.; Weiser, Jeremy; Alyea, Edwin P.; Antin, Joseph H.; Cutler, Corey; Koreth, John; Canning, Christine; Ritz, Jerome; Soiffer, Robert J.; Dranoff, Glenn] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Haesook] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Kim, Haesook] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Kolodin, Dmitriy] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA. [Altevogt, Peter; Kiefel, Helena] German Canc Res Ctr, Translat Immunol, Heidelberg, Germany. RP Dranoff, G (reprint author), Dana Farber Canc Inst, 44 Binney St,Dana 520C,450 Brookline Ave, Boston, MA 02215 USA. EM glenn_dranoff@dfci.harvard.edu OI Piesche, Matthias/0000-0002-9050-1946; Ritz, Jerome/0000-0001-5526-4669 FU Leukemia & Lymphoma Society; NCI [R01CA143083, P01CA78378]; Research Foundation for the Treatment of Ovarian Cancer; Stand Up To Cancer-Cancer Research Institute Cancer Immunology Dream Team Translational Research Grant [SU2C-AACR-DT1012] FX This work was supported with NCI R01CA143083, P01CA78378, the Leukemia & Lymphoma Society, the Research Foundation for the Treatment of Ovarian Cancer, and a Stand Up To Cancer-Cancer Research Institute Cancer Immunology Dream Team Translational Research Grant (SU2C-AACR-DT1012). Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research. NR 50 TC 3 Z9 3 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 MAR PY 2015 VL 21 IS 5 BP 1010 EP 1018 DI 10.1158/1078-0432.CCR-14-1956 PG 9 WC Oncology SC Oncology GA CE6XZ UT WOS:000351982800013 PM 25538258 ER PT J AU Rothenberg, SM McFadden, DG Palmer, EL Daniels, GH Wirth, LJ AF Rothenberg, S. Michael McFadden, David G. Palmer, Edwin L. Daniels, Gilbert H. Wirth, Lori J. TI Redifferentiation of Iodine-Refractory BRAF V600E-Mutant Metastatic Papillary Thyroid Cancer with Dabrafenib SO CLINICAL CANCER RESEARCH LA English DT Article ID BRAF(V600E); EXPRESSION; MUTATION; CARCINOMA; DEDIFFERENTIATION; INHIBITION; PREVALENCE; THERAPY; I-124; GENES AB Purpose: To determine whether the selective BRAF inhibitor, dabrafenib, can stimulate radioiodine uptake in BRAF V600E-mutated unresectable or metastatic iodine-refractory papillary thyroid cancer (PTC). Experimental Design: Ten patients with BRAF V600Emutant iodine-refractory PTC were enrolled. Absence of radioiodine uptake on iodine-131 whole body scan obtained within 14 months of study entry was required. Each patient received dabrafenib (150 mg twice daily) for 25 days before thyrotropin a-stimulated iodine-131 whole body scan (4 mCi/148 MBq). Patients whose scan showed new sites of radioiodine uptake remained on dabrafenib for 17 more days, and then were treated with 150 mCi (5.5 GBq) iodine-131. The primary endpoint of the study was the percentage of patients with new radioiodine uptake after treatment with dabrafenib. Results: Six of 10 patients (60%) demonstrated new radioiodine uptake on whole body scan after treatment with dabrafenib. All 6 were treated with 5.5 GBq iodine-131. Two patients had partial responses and 4 patients had stable disease on standard radiographic restaging at 3 months. Thyroglobulin decreased in 4 of 6 treated patients. One patient developed squamous cell carcinoma of the skin. There were no other significant adverse events attributed to dabrafenib. Conclusions: Dabrafenib can stimulate radioiodine uptake in patients with metastatic BRAF V600E-mutant iodine-refractory PTC, representing a potential new therapeutic approach for these patients. C1 [Rothenberg, S. Michael; McFadden, David G.; Daniels, Gilbert H.; Wirth, Lori J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Rothenberg, S. Michael; McFadden, David G.; Palmer, Edwin L.; Daniels, Gilbert H.; Wirth, Lori J.] Harvard Univ, Sch Med, Boston, MA USA. [Rothenberg, S. Michael; McFadden, David G.; Daniels, Gilbert H.; Wirth, Lori J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [McFadden, David G.; Daniels, Gilbert H.] Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA. [Palmer, Edwin L.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Wirth, LJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey 7B,55 Fruit St, Boston, MA 02114 USA. EM lwirth@mgh.harvard.edu FU GlaxoSmithKline; Ellison Foundation; [K08DE020139]; [K08CA160658] FX This work was supported in part by GlaxoSmithKline and a grant from the Ellison Foundation (to G.H. Daniels). S.M. Rothenberg was supported by K08DE020139 and D.G. McFadden was supported by K08CA160658. NR 25 TC 30 Z9 32 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 2015 VL 21 IS 5 BP 1028 EP 1035 DI 10.1158/1078-0432.CCR-14-2915 PG 8 WC Oncology SC Oncology GA CE6XZ UT WOS:000351982800015 PM 25549723 ER PT J AU Wagner, AJ Messersmith, WA Shaik, MN Li, S Zheng, XX McLachlan, KR Cesari, R Courtney, R Levin, WJ El-Khoueiry, AB AF Wagner, Andrew J. Messersmith, Wells A. Shaik, M. Naveed Li, Sherry Zheng, Xianxian McLachlan, Karen R. Cesari, Rossano Courtney, Rachel Levin, Wendy J. El-Khoueiry, Anthony B. TI A Phase I Study of PF-04449913, an Oral Hedgehog Inhibitor, in Patients with Advanced Solid Tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID PANCREATIC-CANCER; PATHWAY; TARGET; CELLS; CARCINOGENESIS; METASTASIS; CARCINOMAS; ACTIVATION; MECHANISMS; MUTATIONS AB Purpose: To estimate the maximum tolerated dose (MTD) of single-agent PF-04449913, and to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity in patients with advanced tumors. Experimental Design: A 3-3 design was used in this open-label, multicenter, phase I study and dose escalation/de-escalation applied until identification of the MTD. PF-04449913 was orally administered once daily in continuous 28-day treatment cycles. The starting dose was 80 mg. Results: A total of 23 patients were enrolled; 19 were evaluable for first-cycle dose-limiting toxicity (DLT). The first-cycle DLT rate at the 640 mg dose level was 33.3%, and the MTD was estimated to be 320 mg once daily. The recommended phase II dose was not determined. PF-04449913 was generally well tolerated at doses of 80 to 320 mg once daily. The most common treatment-related adverse events (AE) were grade 1-2 dysgeusia, fatigue, decreased appetite, nausea, dizziness, dehydration, and diarrhea. Treatment- related grade 3 AEs only occurred in patients receiving PF-04449913 640 mg once daily. No treatment-related grade 4-5 AEs were reported. Pharmacokinetic analysis indicated a generally dose-proportional kinetics with biphasic elimination, supporting once-daily dosing. PF-04449913 modulated hedgehog signaling at the dose levels tested, as demonstrated by > 80% downregulation of GLI1 expression in the skin of treated patients. Eight patients (34.8%) achieved stable disease; none had complete or partial response. Three patients with disease progression at enrollment had prolonged disease stabilization (> 6 months). Conclusions: The results obtained in this study support further evaluation of PF-04449913 in patients with advanced solid tumors. C1 [Wagner, Andrew J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Messersmith, Wells A.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Shaik, M. Naveed; Zheng, Xianxian; McLachlan, Karen R.; Courtney, Rachel; Levin, Wendy J.] Pfizer Oncol, La Jolla, CA USA. [Li, Sherry] Pfizer China Res & Dev Ctr, Shanghai, Peoples R China. [Cesari, Rossano] Pfizer Oncol, Milan, Italy. [El-Khoueiry, Anthony B.] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. RP Wagner, AJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol,Dept Med, Boston, MA 02215 USA. EM Andrew_Wagner@dfci.harvard.edu FU Pfizer Inc.; Virginia; D.K. Ludwig Fund for Cancer Research FX This study was sponsored by Pfizer Inc. A.J. Wagner was supported by the Virginia and D.K. Ludwig Fund for Cancer Research. Medical writing support was provided by M. Nori and S. Mariani of Engage Scientific Solutions, and was funded by Pfizer Inc. NR 31 TC 9 Z9 9 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 2015 VL 21 IS 5 BP 1044 EP 1051 DI 10.1158/1078-0432.CCR-14-1116 PG 8 WC Oncology SC Oncology GA CE6XZ UT WOS:000351982800017 PM 25388167 ER PT J AU Choueiri, TK Figueroa, DJ Fay, AP Signoretti, S Liu, Y Gagnon, R Deen, K Carpenter, C Benson, P Ho, TH Pandite, L de Souza, P Powles, T Motzer, RJ AF Choueiri, Toni K. Figueroa, David J. Fay, Andre P. Signoretti, Sabina Liu, Yuan Gagnon, Robert Deen, Keith Carpenter, Christopher Benson, Peter Ho, Thai H. Pandite, Lini de Souza, Paul Powles, Thomas Motzer, Robert J. TI Correlation of PD-L1 Tumor Expression and Treatment Outcomes in Patients with Renal Cell Carcinoma Receiving Sunitinib or Pazopanib: Results from COMPARZ, a Randomized Controlled Trial SO CLINICAL CANCER RESEARCH LA English DT Article ID CD8(+) T-LYMPHOCYTES; CANCER; B7-H1; THERAPY; RESISTANCE; PROGNOSIS; MOLECULE; PATHWAY; KIDNEY; LUNG AB Purpose: The interaction of programmed death-1 ligand (PD-L1) with its receptor (PD-1) on T cells inactivates antitumor immune responses. PD-L1 expression has been associated with poor outcomes in renal cell carcinoma (RCC) but has not been investigated in advanced RCC patients receiving vascular endothelial growth factor (VEGF)-targeted therapy. Experimental Design: Formalin-fixed paraffin-embedded (specimens were collected at baseline from patients in the COMPARZ trial. Tumor cell PD-L1 expression by immunohistochemistry was evaluated using H-score (HS). Dual PD-L1/CD68 staining was used to differentiate PD-L1 tumor expression from tumor-associated macrophages. Intratumor CD8-positive T cells were quantified morphometrically. Associations between biomarkers and survival were investigated using the log-rank test. Results: HS data were available from 453 of 1110 patients. Sixty-four percent of patients had negative PD-L1 expression (HS=0). Patients with HS>55 (n=59, 13%) had significantly shorter overall survival (OS) than those with HS=55 in both pazopanib and sunitinib arms (median 15.1 vs 35.6 and 15.3 vs 27.8 months, respectively, P=0.03). In both arms, median OS was shortest in patients with HS>55 and intratumor CD8-positive T-cell counts >300 (9.6 and 11.9 months with pazopanib and sunitinib, respectively). Median OS in patients with HS=55 and CD8-positive T-cell counts =300 was 36.8 and 28.0 months with pazopanib and sunitinib, respectively. Progression-free survival results were similar to OS results. Conclusions: Increased tumor cell PD-L1, or PD-L1 plus tumor CD8-positive T-cell counts, were associated with shorter survival in metastatic RCC patients receiving VEGF-targeted agents. These findings may have implications for future design of randomized clinical trials in advanced RCC. C1 [Choueiri, Toni K.; Fay, Andre P.; Signoretti, Sabina] Harvard Univ, Brigham & Womens Hosp, Sch Med, Kidney Canc Ctr,Dana Farber Canc Inst, Boston, MA 02115 USA. [Figueroa, David J.; Liu, Yuan; Gagnon, Robert; Deen, Keith; Carpenter, Christopher] GlaxoSmithKline, Collegeville, PA USA. [Benson, Peter] MEDTOX Labs, St Paul, MN USA. [Ho, Thai H.] Mayo Clin Arizona, Scottsdale, AZ USA. [Pandite, Lini] GlaxoSmithKline, Res Triangle Pk, NC USA. [de Souza, Paul] Univ Western Sydney, Ingham Inst, Liverpool, NSW, Australia. [Powles, Thomas] Queen Mary Univ London, Barts Expt Canc Med Ctr, Barts Canc Inst, London, England. [Motzer, Robert J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Choueiri, TK (reprint author), Dana Farber Canc Inst, Kidney Canc Ctr, 450 Brookline Ave,DANA 1230, Boston, MA 02215 USA. EM toni_choueiri@dfci.harvard.edu FU GlaxoSmithKline Pharmaceuticals; Trust family; Loker Pinard; Michael Brigham Funds for Kidney Cancer Research at Dana-Farber Cancer Institute; Dana-Farber/Harvard Cancer Center Kidney Cancer Program; Dana-Farber/Harvard Cancer Center Kidney Cancer [SPORE P50 CA101942 01] FX This work was funded in part by GlaxoSmithKline Pharmaceuticals, the Trust family, Loker Pinard, and Michael Brigham Funds for Kidney Cancer Research (to T.K. Choueiri) at Dana-Farber Cancer Institute, the Dana-Farber/Harvard Cancer Center Kidney Cancer Program, and the Dana-Farber/Harvard Cancer Center Kidney Cancer SPORE P50 CA101942 01. NR 34 TC 37 Z9 37 U1 3 U2 16 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 MAR PY 2015 VL 21 IS 5 BP 1071 EP 1077 DI 10.1158/1078-0432.CCR-14-1993 PG 7 WC Oncology SC Oncology GA CE6XZ UT WOS:000351982800020 PM 25538263 ER PT J AU Magbanua, MJM Carey, LA DeLuca, A Hwang, J Scott, JH Rimawi, MF Mayer, EL Marcom, PK Liu, MC Esteva, FJ Park, JW Rugo, HS AF Magbanua, Mark Jesus M. Carey, Lisa A. DeLuca, Amy Hwang, Jimmy Scott, Janet H. Rimawi, Mothaffar F. Mayer, Erica L. Marcom, P. Kelly Liu, Minetta C. Esteva, Francisco J. Park, John W. Rugo, Hope S. CA Translational Breast Canc Res Cons TI Circulating Tumor Cell Analysis in Metastatic Triple-Negative Breast Cancers SO CLINICAL CANCER RESEARCH LA English DT Article ID PERIPHERAL-BLOOD; PROSTATE-CANCER; CHEMOTHERAPY; SURVIVAL; PROGRESSION; TRIAL AB Purpose: Recent developments in rare-cell technology have led to improved blood-based assays that allow for the reliable detection, enumeration, and more recently, genomic profiling of circulating tumor cells (CTC). We evaluated two different approaches for enumeration of CTCs in a prospective therapeutic study of patients with metastatic triple-negative breast cancer (TNBC). Experimental Design: The CellSearch system, a commercially available and U.S. Food and Drug Administration (FDA)-cleared assay for CTC enumeration, and IE/FC, an alternative method using EPCAM-based immunomagnetic enrichment and flow cytometry that maintains cell viability, were used to enumerate CTCs in the blood of patients with metastatic TNBC. CTC numbers were assessed at baseline and 7 to 14 days after initiation of therapy with cetuximab +/- carboplatin in a phase II multicenter clinical trial (TBCRC 001). Results: CTC numbers from two methods were significantly correlated at baseline (r = 0.62) and at 7 to 14 days (r = 0.53). Baseline CTCs showed no association with time-to-progression (TTP), whereas CTCs at 7 to 14 days were significantly correlated with TTP (CellSearch P = 0.02; IE/FC P = 0.03). CTCs at both time points were significantly associated with overall survival (OS) [CellSearch: baseline (P = 0.0001) and 7 to 14 days (P < 0.0001); IE/FC: baseline (P = 0.0009) and 7 to 14 days (P = 0.0086)]. Conclusions: Our findings demonstrate that CTC enumeration by two different assays was highly concordant. In addition, results of both assays were significantly correlated with TTP and OS in patients with TNBC. The IE/FC method is also easily adapted (C)2014 AACR. C1 [Magbanua, Mark Jesus M.; DeLuca, Amy; Hwang, Jimmy; Scott, Janet H.; Park, John W.; Rugo, Hope S.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94115 USA. [Carey, Lisa A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Rimawi, Mothaffar F.] Baylor Univ, Coll Med, Houston, TX 77030 USA. [Mayer, Erica L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Marcom, P. Kelly] Duke Univ, Med Ctr, Durham, NC USA. [Liu, Minetta C.] Georgetown Univ, Washington, DC USA. [Esteva, Francisco J.] NYU, Langone Med Ctr, Laura & Isaac Perlmutter Canc Ctr, New York, NY USA. RP Rugo, HS (reprint author), Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Box 1710 1600 Divisadero St, San Francisco, CA 94115 USA. EM hrugo@medicine.ucsf.edu OI Esteva, Francisco/0000-0003-2437-3920 FU Avon Partners-for-Progress; Bristol-Myers Squibb; Breast Cancer Research Foundation; Avon Foundation; Susan G. Komen for the Cure through the Translational Breast Cancer Research Consortium FX This study was funded by the Avon Partners-for-Progress (to L.A. Carey and H.S. Rugo), and Bristol-Myers Squibb. Veridex provided technology (CellSearch System) and materials for CTC enumeration. Additional funding was provided by the Breast Cancer Research Foundation, the Avon Foundation, and Susan G. Komen for the Cure through the Translational Breast Cancer Research Consortium. NR 34 TC 11 Z9 11 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 2015 VL 21 IS 5 BP 1098 EP 1105 DI 10.1158/1078-0432.CCR-14-1948 PG 8 WC Oncology SC Oncology GA CE6XZ UT WOS:000351982800023 PM 25524311 ER PT J AU Dalva-Aydemir, S Bajpai, R Martinez, M Adekola, KUA Kandela, I Wei, CY Singhal, S Koblinski, JE Raje, NS Rosen, ST Shanmugam, M AF Dalva-Aydemir, Sevim Bajpai, Richa Martinez, Maylyn Adekola, Kehinde U. A. Kandela, Irawati Wei, Changyong Singhal, Seema Koblinski, Jennifer E. Raje, Noopur S. Rosen, Steven T. Shanmugam, Mala TI Targeting the Metabolic Plasticity of Multiple Myeloma with FDA-Approved Ritonavir and Metformin SO CLINICAL CANCER RESEARCH LA English DT Article ID HIV PROTEASE INHIBITORS; CANCER-CELLS; GLUCOSE-METABOLISM; INSULIN-RESISTANCE; RESPIRATORY-CHAIN; MCL-1; SURVIVAL; APOPTOSIS; THERAPY; KINASE AB Purpose: We have previously demonstrated that ritonavir targeting of glycolysis is growth inhibitory and cytotoxic in a subset of multiple myeloma cells. In this study, our objective was to investigate themetabolic basis of resistance to ritonavir and to determine the utility of cotreatment with the mitochondrial complex I inhibitor metformin to target compensatory metabolism. Experimental Design: We determined combination indices for ritonavir and metformin, impact on myeloma cell lines, patient samples, and myeloma xenograft growth. Additional evaluation in breast, melanoma, and ovarian cancer cell lines was also performed. Signaling connected to suppression of the prosurvival BCL-2 family member MCL-1 was evaluated in multiple myeloma cell lines and tumor lysates. Reliance on oxidative metabolism was determined by evaluation of oxygen consumption, and dependence on glutamine was assessed by estimation of viability upon metabolite withdrawal in the context of specific metabolic perturbations. Results: Ritonavir-treated multiple myeloma cells exhibited increased reliance on glutamine metabolism. Ritonavir sensitized multiple myeloma cells to metformin, effectively eliciting cytotoxicity both in vitro and in an in vivo xenograft model of multiple myeloma and in breast, ovarian, and melanoma cancer cell lines. Ritonavir and metformin effectively suppressed AKT and mTORC1 phosphorylation and prosurvival BCL-2 family member MCL-1 expression in multiple myeloma cell lines in vitro and in vivo. Conclusions: FDA-approved ritonavir and metformin effectively target multiple myeloma cell metabolism to elicit cytotoxicity in multiple myeloma. Our studies warrant further investigation into repurposing ritonavir and metformin to target the metabolic plasticity of myeloma to more broadly target myeloma heterogeneity and prevent the reemergence of chemoresistant aggressive multiple myeloma. C1 [Dalva-Aydemir, Sevim; Martinez, Maylyn; Adekola, Kehinde U. A.; Singhal, Seema; Koblinski, Jennifer E.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Bajpai, Richa; Wei, Changyong; Shanmugam, Mala] Emory Univ, Sch Med, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Kandela, Irawati] Northwestern Univ, Chem Life Proc Inst, Chicago, IL 60611 USA. [Singhal, Seema] Northwestern Univ, Feinberg Sch Med, Div Hematol & Oncol, Chicago, IL 60611 USA. [Raje, Noopur S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rosen, Steven T.] City Hope Natl Med Ctr, Duarte, CA USA. RP Shanmugam, M (reprint author), Emory Univ, Sch Med, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. EM mala.shan@emory.edu FU Robert H.L.C.C center; Wendy Will Case Cancer Foundation [SP0012544]; American Cancer Society (IL division) [188679]; American Cancer Society [RSG-11-254-01-CSM]; Robert H. Lurie Cancer Center - NCI CCSG [P30 CA060553] FX This work was supported by Robert H.L.C.C center gift fund (to S.T. Rosen), Wendy Will Case Cancer Foundation grant SP0012544 (to M. Shanmugam), American Cancer Society (IL division grant #188679; to M. Shanmugam), and the American Cancer Society (Research scholar grant RSG-11-254-01-CSM; to M. Shanmugam). All animal studies were performed by Dr. Irawati Kandela and IHC staining by Andrey Ugolkov at the Northwestern University Center for Developmental Therapeutics core funded by the Robert H. Lurie Cancer Center, generously supported by NCI CCSG P30 CA060553 core grant. NR 46 TC 10 Z9 10 U1 4 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 2015 VL 21 IS 5 BP 1161 EP 1171 DI 10.1158/1078-0432.CCR-14-1088 PG 11 WC Oncology SC Oncology GA CE6XZ UT WOS:000351982800029 PM 25542900 ER PT J AU Scott, MG Gronowski, AM Reid, IR Holick, MF Thadhani, R Phinney, K AF Scott, Mitchell G. Gronowski, Ann M. Reid, Ian R. Holick, Michael F. Thadhani, Ravi Phinney, Karen TI Vitamin D: The More We Know, the Less We Know SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 [Scott, Mitchell G.; Gronowski, Ann M.] Washington Univ, Sch Med, Div Lab & Genom Med, St Louis, MO 63110 USA. [Reid, Ian R.] Univ Auckland, Med, Auckland 1, New Zealand. [Holick, Michael F.] Boston Univ, Med Ctr, Bone Hlth Care Clin, Med Physiol & Biophys,Gen Clin Res Unit, Boston, MA 02215 USA. [Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol,Med, Boston, MA 02114 USA. [Phinney, Karen] NIST, Biomol Measurement Div, Grp Leader Bioanalyt Sci, Gaithersburg, MD 20899 USA. RP Gronowski, AM (reprint author), Washington Univ, Sch Med, Div Lab & Genom Med, Box 8118,660 S Euclid, St Louis, MO 63110 USA. EM gronowski@wustl.edu NR 4 TC 7 Z9 8 U1 1 U2 10 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD MAR PY 2015 VL 61 IS 3 BP 462 EP 465 DI 10.1373/clinchem.2014.222521 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA CE9JX UT WOS:000352161300004 PM 25056405 ER PT J AU Lang, RM Badano, LP Mor-Avi, V Afilalo, J Armstrong, A Ernande, L Flachskampf, FA Foster, E Goldstein, SA Kuznetsova, T Lancellotti, P Muraru, D Picard, MH Rietzschel, ER Rudski, L Spencer, KT Tsang, W Voigt, JU AF Lang, Roberto M. Badano, Luigi P. Mor-Avi, Victor Afilalo, Jonathan Armstrong, Anderson Ernande, Laura Flachskampf, Frank A. Foster, Elyse Goldstein, Steven A. Kuznetsova, Tatiana Lancellotti, Patrizio Muraru, Denisa Picard, Michael H. Rietzschel, Ernst R. Rudski, Lawrence Spencer, Kirk T. Tsang, Wendy Voigt, Jens-Uwe TI Recommendations for Cardiac Chamber Quantification by Echocardiography in Adults: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging SO EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING LA English DT Article DE Adult echocardiography; Transthoracic echocardiography; Ventricular function; Normal values ID LEFT ATRIAL VOLUME; AORTIC-VALVE IMPLANTATION; TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY; LEFT-VENTRICULAR MASS; ACUTE MYOCARDIAL-INFARCTION; INFERIOR VENA-CAVA; MULTIDETECTOR COMPUTED-TOMOGRAPHY; SPECKLE-TRACKING ECHOCARDIOGRAPHY; GLOBAL LONGITUDINAL STRAIN; PATIENTS GREATER-THAN-OR-EQUAL-TO-65 YEARS AB The rapid technological developments of the past decade and the changes in echocardiographic practice brought about by these developments have resulted in the need for updated recommendations to the previously published guidelines for cardiac chamber quantification, which was the goal of the joint writing group assembled by the American Society of Echocardiography and the European Association of Cardiovascular Imaging. This document provides updated normal values for all four cardiac chambers, including three-dimensional echocardiography and myocardial deformation, when possible, on the basis of considerably larger numbers of normal subjects, compiled from multiple databases. In addition, this document attempts to eliminate several minor discrepancies that existed between previously published guidelines. C1 [Lang, Roberto M.; Mor-Avi, Victor; Spencer, Kirk T.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Badano, Luigi P.; Muraru, Denisa] Univ Padua, Padua, Italy. [Afilalo, Jonathan; Rudski, Lawrence] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. [Armstrong, Anderson] Johns Hopkins Univ, Baltimore, MD USA. [Ernande, Laura] INSERM U955, Creteil, France. [Ernande, Laura] Hop Henri Mondor, F-94010 Creteil, France. [Flachskampf, Frank A.] Uppsala Univ, Uppsala, Sweden. [Foster, Elyse] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Goldstein, Steven A.] Medstar Washington Hosp Ctr, Washington, DC USA. [Kuznetsova, Tatiana; Voigt, Jens-Uwe] Univ Hosp Leuven, Leuven, Belgium. [Lancellotti, Patrizio] Univ Liege, Liege, Belgium. [Picard, Michael H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Picard, Michael H.] Harvard Univ, Sch Med, Boston, MA USA. [Rietzschel, Ernst R.] Ghent Univ Hosp, Ghent, Belgium. [Tsang, Wendy] Univ Toronto, Toronto, ON, Canada. RP Lang, RM (reprint author), Univ Chicago, Med Ctr, Chicago, IL 60637 USA. OI Mor-Avi, Victor/0000-0001-7932-6473; Badano, Luigi/0000-0002-0379-3283; Picard, Michael/0000-0002-9264-3243 FU GE Healthcare; Siemens; Abbott Vascular Structural Heart; Philips Medical Systems; Esaote FX The following authors reported relationships with one or more commercial interests: Luigi P. Badano, MD, PhD, FESC, received grants from GE Healthcare, Siemens, and Esaote and serves on the speakers' bureau for GE Healthcare. Elyse Foster, MD, FASE, received grant support from Abbott Vascular Structural Heart. Roberto M. Lang, MD, FASE, FESC, received grants from and serves on the speakers' bureau and advisory board for Philips Medical Systems. Denisa Muraru, MD, received research equipment from and served as a consultant for GE Healthcare. Lawrence Rudski, MD, FASE, holds stock in GE. Drs Lang and Badano co-chaired the Writing Group. NR 206 TC 314 Z9 322 U1 11 U2 33 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 2047-2404 EI 2047-2412 J9 EUR HEART J-CARD IMG JI Eur. Heart J.-Cardiovasc. Imaging PD MAR PY 2015 VL 16 IS 3 BP 233 EP 271 DI 10.1093/ehjci/jev014 PG 39 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE9YE UT WOS:000352198800001 PM 25712077 ER PT J AU Dal-Bianco, JP Levine, RA AF Dal-Bianco, Jacob P. Levine, Robert A. TI The mitral valve is an actively adapting tissue: new imaging evidence SO EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING LA English DT Editorial Material ID COMPENSATORY MECHANISM; LEAFLET ADAPTATION; HEART-FAILURE; REGURGITATION; CARDIOMYOPATHY; ANATOMY; MATRIX C1 [Dal-Bianco, Jacob P.; Levine, Robert A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Dal-Bianco, JP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St,Yawkey 5E, Boston, MA 02114 USA. EM jdalbianco@partners.org FU NHLBI NIH HHS [R01 HL72265, K24 HL67434, HL109506] NR 15 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 2047-2404 EI 2047-2412 J9 EUR HEART J-CARD IMG JI Eur. Heart J.-Cardiovasc. Imaging PD MAR PY 2015 VL 16 IS 3 BP 286 EP 287 DI 10.1093/ehjci/jeu300 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE9YE UT WOS:000352198800007 PM 25617031 ER PT J AU Redler, S Petukhova, L Ripke, S Huang, H Menelaou, A Becker, T Heilmann, S Yamany, T Duvic, M Hordinsky, M Norris, D Price, V Mackay-Wiggan, J de Jong, A DeStefano, G Moebus, S Bohm, M Blume-Peytavi, U Wolff, H Lutz, G Kruse, R Bian, L Amos, C Lee, A Gregersen, P Blaumeiser, B Altshuler, D Clynes, R de Bakker, PI Nothen, MM Daly, MJ Christiano, AM Betz, RC AF Redler, S. Petukhova, L. Ripke, S. Huang, H. Menelaou, A. Becker, T. Heilmann, S. Yamany, T. Duvic, M. Hordinsky, M. Norris, D. Price, V. Mackay-Wiggan, J. de Jong, A. DeStefano, G. Moebus, S. Boehm, M. Blume-Peytavi, U. Wolff, H. Lutz, G. Kruse, R. Bian, L. Amos, C. Lee, A. Gregersen, P. Blaumeiser, B. Altshuler, D. Clynes, R. de Bakker, P. I. Noethen, M. M. Daly, M. J. Christiano, A. M. Betz, R. C. TI Meta-analysis of genome-wide association studies in alopecia areata resolves HLA associations and reveals two new susceptibility loci SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung (ADF) CY MAR 05-07, 2015 CL Ulm, GERMANY SP Arbeitsgemeinschaft Dermatologische Forsch C1 [Redler, S.; Heilmann, S.; Noethen, M. M.; Betz, R. C.] Univ Bonn, Inst Human Genet, Bonn, Germany. [Petukhova, L.; Yamany, T.; Mackay-Wiggan, J.; de Jong, A.; Bian, L.; Clynes, R.; Christiano, A. M.] Columbia Univ, Dept Dermatol, New York, NY 10027 USA. [Petukhova, L.] Columbia Univ, Dept Epidemiol, New York, NY USA. [Ripke, S.; Huang, H.; Altshuler, D.; Daly, M. J.] Massachusetts Gen Hosp, Analyt & Transfat Genet Unit, Boston, MA 02114 USA. [Ripke, S.; Huang, H.; Altshuler, D.; Daly, M. J.] Harvard Univ, Sch Med, Boston, MA USA. [Ripke, S.; Huang, H.; Altshuler, D.; Daly, M. J.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Menelaou, A.; de Bakker, P. I.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Becker, T.] German Ctr Neurodegenerat Dis, Bonn, Germany. [Becker, T.] Univ Bonn, Inst Med Biometry Informat & Epidemiol, Bonn, Germany. [Heilmann, S.; Noethen, M. M.] Univ Bonn, Dept Genom, Life & Brain Ctr, Boston, Germany. [Duvic, M.] Univ Texas MD Anderson Canc Ctr, Dept Dermatol, Houston, TX 77030 USA. [Hordinsky, M.] Univ Minnesota, Dept Dermatol, Minneapolis, MN 55455 USA. [Norris, D.] Univ Colorado, Dept Dermatol, Boulder, CO 80309 USA. [Price, V.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [DeStefano, G.; Christiano, A. M.] Columbia Univ, Dept Genet & Dev, New York, NY USA. [Moebus, S.] Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany. [Boehm, M.] Univ Munster, Dept Dermatol, D-48149 Munster, Germany. [Blume-Peytavi, U.] Charite, Dept Dermatol & Allergy, Clin Res Ctr Hair & Skin Sci, D-13353 Berlin, Germany. [Wolff, H.] Univ Munich, Dept Dermatol, D-80539 Munich, Germany. [Amos, C.] Dartmouth Coll, Community & Family Med & Genet, Hanover, NH 03755 USA. [Lee, A.; Gregersen, P.] Feinstein Inst Med Res, Manhasset, NY USA. [Blaumeiser, B.] Univ Antwerp, Dept Med Genet, B-2020 Antwerp, Belgium. [Clynes, R.] Columbia Univ, Dept Med, New York, NY USA. [de Bakker, P. I.] Univ Med Ctr Utrecht, Dept Epidemiol, Utrecht, Netherlands. RI de Bakker, Paul/B-8730-2009 OI de Bakker, Paul/0000-0001-7735-7858 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0906-6705 EI 1600-0625 J9 EXP DERMATOL JI Exp. Dermatol. PD MAR PY 2015 VL 24 IS 3 MA P097 BP E17 EP E17 PG 1 WC Dermatology SC Dermatology GA CE6IB UT WOS:000351939000098 ER PT J AU An, G Acharya, C Deng, SH Yi, SH Xu, Y Qin, XQ Sui, WW Li, ZJ Shi, LH Zang, MR Feng, XY Hao, M Zou, DH Zhao, YZ Qi, JY Cheng, T Ru, K Wang, JX Tai, YT Qiu, LG AF An, Gang Acharya, Chirag Deng, Shuhui Yi, Shuhua Xu, Yan Qin, Xiaoqi Sui, Weiwei Li, Zengjun Shi, Lihui Zang, Meirong Feng, Xiaoyan Hao, Mu Zou, Dehui Zhao, Yaozhong Qi, Junyuan Cheng, Tao Ru, Kun Wang, Jianxiang Tai, Yu-Tzu Qiu, Lugui TI Cytogenetic and clinical marks for defining high-risk myeloma in the context of bortezomib treatment SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID STEM-CELL TRANSPLANTATION; LENALIDOMIDE PLUS DEXAMETHASONE; MULTIPLE-MYELOMA; DELETION; PROGNOSIS; SURVIVAL; T(4/14); CLASSIFICATION; ABNORMALITIES; CHEMOTHERAPY AB Multiple myeloma (MM) is a heterogeneous disease, and the benefit from bortezomib treatment is not uniform among all patients subgroups. Currently, little inform-nation is available to predict patients response to bortezomib treatment. In this study, we aimed to identify patients benefiting minimally from bortezomib as part of first-line therapy and to define high-risk MM in the context of bortezomib treatment. We compared the effect of a bortezomib-based treatment (arm B) with that of a treatment without bortezomib (arm A) on different genetic patient subgroups in a series of 273 cases of newly diagnosed MM. These patients were enrolled in a prospective, non-randomized clinical trial (BDH 2008/02). A subgroup of patients exhibiting little benefit from bortezomib treatment was identified. These patients had at least one of the following characteristics: del(17p13), 1q21 gain, or high lactate dehydrogenase levels. In this subgroup, survival of patients treated with bortezomib was comparable (progression-free survival: 14.0 vs. 15.0 months, p = 0.992; overall survival: 21.0 vs. 14.0 months,p = 0.472) to that of patients undergoing thalidomide-based treatment. We propose that all patients with newly diagnosed MM should be evaluated for these three markers before bortezomib treatment. Other novel drugs and alternative therapeutic strategies are needed for patients with such markers. Copyright (C) 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. C1 [An, Gang; Deng, Shuhui; Yi, Shuhua; Xu, Yan; Qin, Xiaoqi; Sui, Weiwei; Li, Zengjun; Shi, Lihui; Zang, Meirong; Feng, Xiaoyan; Hao, Mu; Zou, Dehui; Zhao, Yaozhong; Qi, Junyuan; Cheng, Tao; Ru, Kun; Wang, Jianxiang; Qiu, Lugui] Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China. [An, Gang; Deng, Shuhui; Yi, Shuhua; Xu, Yan; Qin, Xiaoqi; Sui, Weiwei; Li, Zengjun; Shi, Lihui; Zang, Meirong; Feng, Xiaoyan; Hao, Mu; Zou, Dehui; Zhao, Yaozhong; Qi, Junyuan; Cheng, Tao; Ru, Kun; Wang, Jianxiang; Qiu, Lugui] Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China. [An, Gang; Deng, Shuhui; Yi, Shuhua; Xu, Yan; Qin, Xiaoqi; Sui, Weiwei; Li, Zengjun; Shi, Lihui; Zang, Meirong; Feng, Xiaoyan; Hao, Mu; Zou, Dehui; Zhao, Yaozhong; Qi, Junyuan; Cheng, Tao; Ru, Kun; Wang, Jianxiang; Qiu, Lugui] Peking Union Med Coll, Tianjin, Peoples R China. [Acharya, Chirag; Tai, Yu-Tzu] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Acharya, Chirag; Tai, Yu-Tzu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Qiu, LG (reprint author), Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China. EM drqiu99@medmail.com.cn FU National Natural Science Fund [81400175, 81172255, 81370632]; Clinical Research Program of the Ministry of Health (Key Project); Special Key Anticancer Research and Development Program of Tianjin Municipality [12ZCDZSY17600]; Union Youth Research Fund of Peking Union Medical College; Doctoral Foundation [20131106120037] FX This study was supported by the National Natural Science Fund (81400175, 81172255, 81370632), the Clinical Research Program of the Ministry of Health (Key Project 2010 to 2012), the Special Key Anticancer Research and Development Program of Tianjin Municipality (12ZCDZSY17600), the Union Youth Research Fund of Peking Union Medical College (2012-2013), and the Doctoral Foundation (20131106120037) NR 29 TC 1 Z9 1 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X EI 1873-2399 J9 EXP HEMATOL JI Exp. Hematol. PD MAR PY 2015 VL 43 IS 3 BP 168 EP 176 DI 10.1016/j.exphem.2014.11.004 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA CE9PZ UT WOS:000352177200003 PM 25462022 ER PT J AU Vanegas, JC Afeiche, MC Gaskins, AJ Minguez-Alarcon, L Williams, PL Wright, DL Toth, TL Hauser, R Chavarro, JE AF Vanegas, Jose C. Afeiche, Myriam C. Gaskins, Audrey J. Minguez-Alarcon, Lidia Williams, Paige L. Wright, Diane L. Toth, Thomas L. Hauser, Russ Chavarro, Jorge E. TI Soy food intake and treatment outcomes of women undergoing assisted reproductive technology SO FERTILITY AND STERILITY LA English DT Article DE Cohort studies; isoflavones; phytoestrogens; soy foods; assisted reproductive techniques ID ESTROGEN-RECEPTOR-ALPHA; DIETARY PATTERNS; RANDOMIZED-TRIAL; SEMEN QUALITY; MEN; PHYTOESTROGEN; INFERTILITY; CELLS; PREGNANCY; AGONIST AB Objective: To study the relation of dietary phytoestrogens intake and clinical outcomes of women undergoing infertility treatment with the use of assisted reproductive technology (ART). Design: Prospective cohort study. Setting: Fertility center. Patient(s): A total of 315 women who collectively underwent 520 ART cycles from 2007 to 2013. Intervention(s): None. Main Outcome Measure(s): Implantation, clinical pregnancy, and live birth rates per initiated cycle. Result(s): Soy isoflavones intake was positively related to live birth rates in ART. Compared with women who did not consume soy isoflavones, the multivariable-adjusted odds ratios of live birth (95% confidence interval) for women in increasing categories of soy isoflavones intake were 1.32 (0.76-2.27) for women consuming 0.54-2.63 mg/d, 1.87 (1.12-3.14) for women consuming 2.64-7.55 mg/d, and 1.77 (1.03-3.03) for women consuming 7.56-27.89 mg/d. Conclusion(s): Dietary soy intake was positively related to the probability of having a live birth during infertility treatment with ART. ((c) 2015 by American Society for Reproductive Medicine.) C1 [Vanegas, Jose C.] Pontificia Univ Javeriana, Sch Med, Bogota, Colombia. [Afeiche, Myriam C.; Minguez-Alarcon, Lidia; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Gaskins, Audrey J.; Chavarro, Jorge E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Gaskins, Audrey J.; Hauser, Russ; Chavarro, Jorge E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Wright, Diane L.; Toth, Thomas L.; Hauser, Russ] Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Wright, Diane L.; Toth, Thomas L.; Hauser, Russ; Chavarro, Jorge E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chavarro, Jorge E.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. RP Chavarro, JE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM jchavarr@hsph.harvard.edu FU National Institutes of Health [ES022955, R01ES009718, R01ES000002, P30DK46200, T32DK007703] FX Supported by National Institutes of Health grants ES022955, R01ES009718, R01ES000002, P30DK46200, and T32DK007703. NR 28 TC 4 Z9 4 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD MAR PY 2015 VL 103 IS 3 BP 749 EP U467 DI 10.1016/j.fertnstert.2014.12.104 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CE8QN UT WOS:000352109000029 PM 25577465 ER PT J AU Merker, VL Murphy, TP Hughes, JB Muzikansky, A Hughes, MR Souter, I Plotkin, SR AF Merker, Vanessa L. Murphy, Timothy P. Hughes, J. Bryan Muzikansky, Alona Hughes, Mark R. Souter, Irene Plotkin, Scott R. TI Outcomes of preimplantation genetic diagnosis in neurofibromatosis type 1 SO FERTILITY AND STERILITY LA English DT Article DE PGD; NF1; fertility; pregnancy; in vitro fertilization; genetic counseling ID DNA AMPLIFICATION; BLASTOCYST BIOPSY; DATA-COLLECTION; HUMAN EMBRYOS; EXPERIENCE; CYCLES; PGD; FERTILIZATION; DEFECTS; BIRTH AB Objective: To examine the effect of patient and facility level factors on the success of preimplantation genetic diagnosis (PGD) in patients with neurofibromatosis 1 (NF1). Design: Retrospective review. Setting: Large PGD reference laboratory. Patient(s): All patients with NF1 referred from June 2004 to May 2013. Intervention(s): None. Main Outcome Measure(s): Embryos' NF1 mutation status and live birth rates. Result(s): Seventy-seven couples underwent 156 PGD cycles during the study period. The average maternal age at the time of embryo biopsy was 33.2 years. The majority of embryos had a day 3 single blastomere biopsy without aneuploidy screening. A diagnosis was obtained for 80% of biopsied embryos; 20% of biopsies were nondiagnostic due to technical failures. Diagnosis was more often obtained for embryos of parents with familial disease and for embryos biopsied at centers that referred multiple NF1 cases. Among diagnosed embryos, 483/1,060 (46%) were unaffected by the parental NF1 mutation. Twenty-two (14%) of the 156 cycles had a confirmed live birth; if the observed success rate is applied to cycles with unknown outcomes, 33/156 (21%) cycles are expected to have resulted in live birth. In multivariate logistic regression, having a live birth was significantly associated with having more unaffected embryos available for transfer (odds ratio 1.33 per additional embryo, 95% confidence interval 1.02-1.72). Conclusion(s): Advances in biopsy and diagnostic techniques which increase the number of unaffected embryos identified may improve live birth rates for patients with NF1. Clinicians should counsel patients about their fertility and reproductive options early, with the use of disease-specific data, to set appropriate expectations for the PGD process. ((c) 2015 by American Society for Reproductive Medicine.) C1 [Merker, Vanessa L.; Murphy, Timothy P.; Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Merker, Vanessa L.; Murphy, Timothy P.; Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Souter, Irene] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Hughes, J. Bryan; Hughes, Mark R.] Genesis Genet, Plymouth, MI USA. RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM splotkin@mgh.harvard.edu OI Merker, Vanessa/0000-0002-4542-5227 FU Alvan T. and Viola D. Fuller-American Cancer Society FX V.L.M. received travel expenses from Genesis Genetics. T.P.M. received funding from the Alvan T. and Viola D. Fuller-American Cancer Society Junior Research Fellowship. J.B.H. is employed by Genesis Genetics. A.M. has nothing to disclose. M.R.H. has a financial interest in Genesis Genetics. I.S. has nothing to disclose. S.R.P. has nothing to disclose. NR 26 TC 1 Z9 2 U1 4 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD MAR PY 2015 VL 103 IS 3 BP 761 EP U481 DI 10.1016/j.fertnstert.2014.11.021 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CE8QN UT WOS:000352109000031 PM 25557241 ER PT J AU Von Delft, A Dramowski, A Khosa, C Kotze, K Lederer, P Mosidi, T Peters, JA Smith, J van der Westhuizen, HM von Delft, D Willems, B Bates, M Craig, G Maeurer, M Marais, BJ Mwaba, P Nunes, EA Nyirenda, T Oliver, M Zumla, A AF von Delft, Arne Dramowski, Angela Khosa, Celso Kotze, Koot Lederer, Philip Mosidi, Thato Peters, Jurgens A. Smith, Jonathan van der Westhuizen, Helene-Mari von Delft, Dalene Willems, Bart Bates, Matthew Craig, Gill Maeurer, Markus Marais, Ben J. Mwaba, Peter Nunes, Elizabete A. Nyirenda, Thomas Oliver, Matt Zumla, Alimuddin TI Why healthcare workers are sick of TB SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Tuberculosis (TB); Multidrug- & Extensively Drug-Resistant TB (MDR-TB & XDR-TB); Healthcare worker (occupational); Infection control; Prevention; Stigma ID DRUG-RESISTANT TUBERCULOSIS; MULTIDRUG-RESISTANT; SOUTH-AFRICA; MDR-TB; XDR-TB; FLUOROQUINOLONES; METAANALYSIS; BEHAVIOR; SPREAD; MALAWI AB Dr Thato Mosidi never expected to be diagnosed with tuberculosis (TB), despite widely prevalent exposure and very limited infection control measures. The life-threatening diagnosis of primary extensively drug-resistant TB (XDR-TB) came as an even greater shock. The inconvenient truth is that, rather than being protected, Dr Mosidi and thousands of her healthcare colleagues are at an increased risk of TB and especially drug-resistant TB. In this viewpoint paper we debunk the widely held false belief that healthcare workers are somehow immune to TB disease (TB-proof) and explore some of the key factors contributing to the pervasive stigmatization and subsequent non-disclosure of occupational TB. Our front-line workers are some of the first to suffer the consequences of a progressively more resistant and fatal TB epidemic, and urgent interventions are needed to ensure the safety and continued availability of these precious healthcare resources. These include the rapid development and scale-up of improved diagnostic and treatment options, strengthened infection control measures, and focused interventions to tackle stigma and discrimination in all its forms. We call our colleagues to action to protect themselves and those they care for. (c) 2014 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. C1 [von Delft, Arne; Dramowski, Angela; Khosa, Celso; Kotze, Koot; Lederer, Philip; Mosidi, Thato; Peters, Jurgens A.; Smith, Jonathan; van der Westhuizen, Helene-Mari; von Delft, Dalene; Willems, Bart; Zumla, Alimuddin] TB Proof, New York, NY 10010 USA. [von Delft, Arne] Univ Cape Town, Fac Hlth Sci, Sch Publ Hlth & Family Med, ZA-7925 Cape Town, South Africa. [Dramowski, Angela] Univ Stellenbosch, Dept Paediat & Child Hlth, Paediat Infect Dis, Cape Town, South Africa. [Khosa, Celso] Minist Hlth, Inst Nacl Saude, Maputo, Mozambique. [Kotze, Koot; van der Westhuizen, Helene-Mari; Willems, Bart] Univ Stellenbosch, Div Community Hlth, Cape Town, South Africa. [Lederer, Philip] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Mosidi, Thato] Resp & Meningeal Pathogens Unit, Wits Hlth Consortium, Johannesburg, South Africa. [Smith, Jonathan] Emory Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA USA. [Smith, Jonathan] Yale Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT USA. [Smith, Jonathan] Visual Epidemiol, New Haven, CT USA. [Bates, Matthew] Univ Teaching Hosp, UNZA UCLMS Project, Lusaka, Zambia. [Smith, Jonathan] City Univ London, London EC1V 0HB, England. [Maeurer, Markus] Karolinska Inst, Stockholm, Sweden. [Marais, Ben J.] Univ Sydney, Childrens Hosp Westmead, Sydney, NSW 2006, Australia. [Marais, Ben J.] Univ Sydney, Marie Bashir Inst Infect Dis & Biosecur MBI, Sydney, NSW 2006, Australia. [Nunes, Elizabete A.] Maputo Cent Hosp, Maputo, Mozambique. [Nyirenda, Thomas] European & Developing Countries Clin Trials Partn, Cape Town, South Africa. [Oliver, Matt] UK All Party Parliamentary Grp Global TB, London, England. [Zumla, Alimuddin] UCL, Div Infect & Immun, London, England. [Zumla, Alimuddin] Univ Coll London Hosp, NIHR Biomed Res Ctr, London, England. RP Von Delft, A (reprint author), TB Proof, New York, NY 10010 USA. EM vuzumsi@gmail.com OI Zumla, Alimuddin/0000-0002-5111-5735 NR 39 TC 12 Z9 13 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 EI 1878-3511 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD MAR PY 2015 VL 32 SI SI BP 147 EP 151 DI 10.1016/j.ijid.2014.12.003 PG 5 WC Infectious Diseases SC Infectious Diseases GA CF2TW UT WOS:000352401500025 PM 25809771 ER PT J AU Schnabolk, G Coughlin, B Joseph, K Kunchithapautham, K Bandyopadhyay, M O'Quinn, EC Nowling, T Rohrer, B AF Schnabolk, Gloriane Coughlin, Beth Joseph, Kusumam Kunchithapautham, Kannan Bandyopadhyay, Mausumi O'Quinn, Elizabeth C. Nowling, Tamara Rohrer, Baerbel TI Local Production of the Alternative Pathway Component Factor B Is Sufficient to Promote Laser-Induced Choroidal Neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE alternative complement pathway; complement factor B; RPE-specific transgenic mouse; choroidal neovascularization; age-related macular degeneration ID COMPLEMENT FACTOR-H; PIGMENT EPITHELIAL-CELLS; MACULAR DEGENERATION; OXIDATIVE STRESS; MEDIATED INJURY; LECTIN PATHWAY; MOUSE MODEL; AGE; ACTIVATION; RISK AB PURPOSE. Complement factor B (CFB) is a required component of the alternative pathway (AP) of complement, and CFB polymorphisms are associated with age-related macular degeneration (AMD) risk. Complement factor B is made in the liver, but expression has also been detected in retina and retinal pigment epithelium (RPE)-choroid. We investigated whether production of CFB by the RPE can promote AP activation in mouse choroidal neovascularization (CNV). METHODS. Transgenic mice expressing CFB under the RPE65 promoter were generated and crossed onto factor B-deficient (CFB-KO) mice. Biological activity was determined in vitro using RPE monolayers and in vivo using laser-induced CNV. Contribution of systemic CFB was investigated using CFB-KO reconstituted with CFB-sufficient serum. RESULTS. Transgenic mice (CFB-tg) expressed CFB in RPE-choroid; no CFB was detected in serum. Cultured CFB-tg RPE monolayers secreted CFB apically and basally upon exposure to oxidative stress that was biologically active. Choroidal neovascularization sizes were comparable between wild-type and CFB-tg mice, but significantly increased when compared to lesions in CFB-KO mice. Injections of CFB-sufficient serum into CFB-KO mice resulted in partial reconstitution of systemic AP activity and significantly increased CNV size. CONCLUSIONS. Mouse RPE cells express and secrete CFB sufficient to promote RPE damage and CNV. This further supports that local complement production may regulate disease processes; however, the reconstitution experiments suggest that additional components may be sequestered from the bloodstream. Understanding the process of ocular complement production and regulation will further our understanding of the AMD disease process and the requirements of a complement-based therapeutic. C1 [Schnabolk, Gloriane; Rohrer, Baerbel] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA. [Coughlin, Beth; Joseph, Kusumam; Kunchithapautham, Kannan; Bandyopadhyay, Mausumi; O'Quinn, Elizabeth C.; Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. [Nowling, Tamara] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. RP Rohrer, B (reprint author), Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA. EM rohrer@musc.edu FU National Institutes of Health (NIH) [R01EY019320]; Department for Veteran Affairs Merit Award [RX000444]; Beckman Initiative for Macular Research; Medical University of South Carolina from Research to Prevent Blindness (RPB), New York, New York, United States; NIH [C06RR015455]; [AR053376]; [R03-NIAMS] FX Supported in the laboratory of BR in part by the National Institutes of Health (NIH R01EY019320); Department for Veteran Affairs Merit Award RX000444; the Beckman Initiative for Macular Research; an unrestricted grant to the Medical University of South Carolina from Research to Prevent Blindness (RPB), New York, New York, United States; and in the laboratory of TN by Grant AR053376 (R03-NIAMS). Animal studies were conducted in a facility constructed with support from NIH C06RR015455. NR 50 TC 3 Z9 3 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2015 VL 56 IS 3 BP 1850 EP 1863 DI 10.1167/iovs.14-15910 PG 14 WC Ophthalmology SC Ophthalmology GA CE9BF UT WOS:000352137600057 PM 25593023 ER PT J AU Jalbert, JJ Nguyen, LL Gerhard-Herman, MD Jaff, MR White, CJ Rothman, AT Seeger, JD Kumamaru, H Williams, LA Chen, CY Liu, J Tsai, TT Aronow, HD Johnston, JA Brott, TG Setoguchi, S AF Jalbert, Jessica J. Nguyen, Louis L. Gerhard-Herman, Marie D. Jaff, Michael R. White, Christopher J. Rothman, Andrew T. Seeger, John D. Kumamaru, Hiraku Williams, Lauren A. Chen, Chih-Ying Liu, Jun Tsai, Thomas T. Aronow, Herbert D. Johnston, Joseph A. Brott, Thomas G. Setoguchi, Soko TI Outcomes After Carotid Artery Stenting in Medicare Beneficiaries, 2005 to 2009 SO JAMA NEUROLOGY LA English DT Article ID LEAD-IN PHASE; REVASCULARIZATION ENDARTERECTOMY; SUBGROUP ANALYSIS; CLINICAL-TRIAL; 30-DAY STROKE; RISK-FACTORS; DEATH RATES; ANGIOPLASTY; STENOSIS; REGISTRY AB IMPORTANCE Despite increased carotid artery stenting (CAS) dissemination following the 2005 National Coverage Determination, to our knowledge, periprocedural and long-term outcomes have not been described among Medicare beneficiaries. OBJECTIVE To describe the incidence of outcomes during and after the periprocedural period among Medicare beneficiaries undergoing CAS. DESIGN, SETTING, AND PARTICIPANTS Observational study with a mean follow-up time of approximately 2 years among 22 516 fee-for-service Medicare beneficiaries at least 66 years old undergoing CAS (2005-2009) who were linked to the Centers for Medicare & Medicaid Services' CAS database. Database procedure dates were required to fall during a Medicare hospitalization for CAS. MAIN OUTCOMES AND MEASURES Periprocedural (30-day) and long-term risks of mortality and stroke or transient ischemic attack, as well as periprocedural myocardial infarction. Subgroups were based on sociodemographic, clinical, and center-level factors, as well as the Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial or Carotid Revascularization Endarterectomy vs Stenting Trial (CREST) enrollment criteria. RESULTS The mean patient age was 76.3 years, 60.5% were male, 93.8% were of white race, 91.2% were at high surgical risk, 47.4% were symptomatic, and 97.4% had carotid stenosis of at least 70%. Crude 30-day mortality, stroke or transient ischemic attack, and myocardial infarction risks were 1.7%(95% CI, 1.5%-1.8%), 3.3%(95% CI, 3.0%-3.5%), and 2.5%(95% CI, 2.3%-2.7%), respectively. Mortality during a mean follow-up time of 2 years was 32.0% (95% CI, 31.0%-33.0%), with rates of 37.3%(95% CI, 35.8%-38.7%) among symptomatic patients and 27.7%(95% CI, 26.4%-28.9%) among asymptomatic patients. Older age, symptomatic carotid stenosis, and nonelective hospital admission were associated with increased adjusted hazards of mortality and stroke or transient ischemic attack during and after the periprocedural period. The presence of a stroke center, government ownership, and a hospital bed capacity of 500 or more were associated with increased adjusted hazards of periprocedural mortality and stroke or transient ischemic attack. Few patients met the SAPPHIRE trial or CREST enrollment criteria primarily because physicians did not meet proficiency requirements either due to exceeding periprocedural complication trial thresholds or not meeting minimum CAS volume requirements. CONCLUSIONS AND RELEVANCE Competing risks may limit the benefits of CAS in certain Medicare beneficiaries, particularly among older and symptomatic patients who have higher periprocedural and long-term mortality risks. The generalizability of trials like the SAPPHIRE or CREST to the Medicare population may be limited, underscoring the need to evaluate real-world effectiveness of carotid stenosis treatments. C1 [Jalbert, Jessica J.; Rothman, Andrew T.; Seeger, John D.; Kumamaru, Hiraku; Williams, Lauren A.; Chen, Chih-Ying; Liu, Jun; Setoguchi, Soko] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol, Boston, MA 02115 USA. [Jalbert, Jessica J.] LASER ANALYT, New York, NY USA. [Nguyen, Louis L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Vasc & Endovasc Surg, Boston, MA 02115 USA. [Gerhard-Herman, Marie D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Div Cardiovasc Med, Boston, MA 02114 USA. [White, Christopher J.] Ochsner Med Ctr, Ochsner Clin Sch, New Orleans, LA USA. [Seeger, John D.] Optumlnsight Epidemiol, Waltham, MA USA. [Tsai, Thomas T.] Univ Colorado, Denver Vet Affairs Med Ctr, Div Cardiol, Denver, CO 80202 USA. [Aronow, Herbert D.] St Joseph Mercy Ann Arbor, Div Cardiovasc Med, Ann Arbor, MI USA. [Johnston, Joseph A.] Eli Lilly & Co, Lilly Res Labs, Global Hlth Outcomes, Indianapolis, IN 46285 USA. [Brott, Thomas G.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Setoguchi, Soko] Duke Clin Res Inst, Dept Med, Durham, NC USA. RP Setoguchi, S (reprint author), Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA. EM soko@post.harvard.edu RI White, Christopher/J-6686-2012 OI White, Christopher/0000-0001-8618-7539 FU Agency for Healthcare Research and Quality, US Department of Health and Human Services, as part of the Developing Evidence to Inform Decisions About Effectiveness Network [HHSA290-2005-0016-I-T08]; Centers for Medicare & Medicaid Services, US Department of Health and Human Services [500-2010-00001I-T06, 500-2010-00001I T02] FX This project is funded by contract HHSA290-2005-0016-I-T08 from the Agency for Healthcare Research and Quality, US Department of Health and Human Services, as part of the Developing Evidence to Inform Decisions About Effectiveness Network and by interagency agreement contract 500-2010-00001I-T06 and carotid endarterectomy contract 500-2010-00001I T02 from the Centers for Medicare & Medicaid Services, US Department of Health and Human Services. NR 39 TC 16 Z9 17 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD MAR PY 2015 VL 72 IS 3 BP 276 EP 286 DI 10.1001/jamaneurol.2014.3638 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA CE9IJ UT WOS:000352157200007 PM 25580726 ER PT J AU Fleisher, AS Chen, KW Quiroz, YT Jakimovich, LJ Gomez, MG Langois, CM Langbaum, JBS Roontiva, A Thiyyagura, P Lee, W Ayutyanont, N Lopez, L Moreno, S Munoz, C Tirado, V Acosta-Baena, N Fagan, AM Giraldo, M Garcia, G Huentelman, MJ Tariot, PN Lopera, F Reiman, EM AF Fleisher, Adam S. Chen, Kewei Quiroz, Yakeel T. Jakimovich, Laura J. Gutierrez Gomez, Madelyn Langois, Carolyn M. Langbaum, Jessica B. S. Roontiva, Auttawut Thiyyagura, Pradeep Lee, Wendy Ayutyanont, Napatkamon Lopez, Liliana Moreno, Sonia Munoz, Claudia Tirado, Victoria Acosta-Baena, Natalia Fagan, Anne M. Giraldo, Margarita Garcia, Gloria Huentelman, Matthew J. Tariot, Pierre N. Lopera, Francisco Reiman, Eric M. TI Associations Between Biomarkers and Age in the Presenilin 1 E280A Autosomal Dominant Alzheimer Disease Kindred A Cross-sectional Study SO JAMA NEUROLOGY LA English DT Article ID AMYLOID-BETA DEPOSITION; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; MUTATION CARRIERS; APOLIPOPROTEIN-E; BRAIN; MRI; RECOMMENDATIONS; WORKGROUPS; DEMENTIA AB IMPORTANCE Age-associated changes in brain imaging and fluid biomarkers are characterized and compared in presenilin 1 (PSEN1) E280A mutation carriers and noncarriers from the world's largest known autosomal dominant Alzheimer disease (AD) kindred. OBJECTIVE To characterize and compare age-associated changes in brain imaging and fluid biomarkers in PSEN1 E280A mutation carriers and noncarriers. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional measures of F-18-florbetapir positron emission tomography, F-18-fludeoxyglucose positron emission tomography, structural magnetic resonance imaging, cerebrospinal fluid (CSF), and plasma biomarkers of AD were assessed from 54 PSEN1 E280A kindred members (age range, 20-59 years). MAIN OUTCOMES AND MEASURES We used brain mapping algorithms to compare regional cerebral metabolic rates for glucose and gray matter volumes in cognitively unimpaired mutation carriers and noncarriers. We used regression analyses to characterize associations between age and the mean cortical to pontine F-18-florbetapir standard uptake value ratios, precuneus cerebral metabolic rates for glucose, hippocampal gray matter volume, CSF A beta 1-42, total tau and phosphorylated tau(181), and plasma A beta measurements. Age at onset of progressive biomarker changes that distinguish carriers from noncarriers was estimated using best-fitting regression models. RESULTS Compared with noncarriers, cognitively unimpaired mutation carriers had significantly lower precuneus cerebral metabolic rates for glucose, smaller hippocampal volume, lower CSF A beta 1-42, higher CSF total tau and phosphorylated tau(181), and higher plasma A beta 1-42 measurements. Sequential changes in biomarkers were seen at age 20 years (95% CI, 14-24 years) for CSF A beta 1-42, age 16 years (95% CI, 11-24 years) for the mean cortical F-18-florbetapir standard uptake value ratio, age 15 years (95% CI, 10-24 years) for precuneus cerebral metabolic rate for glucose, age 15 years (95% CI, 7-20 years) for CSF total tau, age 13 years (95% CI, 8-19 years) for phosphorylated tau181, and age 6 years (95% CI, 1-10 years) for hippocampal volume, with cognitive decline up to 6 years before the kindred's estimated median age of 44 years (95% CI, 43-45 years) at mild cognitive impairment diagnosis. No age-associated findings were seen in plasma A beta 1-42 or A beta 1-40. CONCLUSIONS AND RELEVANCE This cross-sectional study provides additional information about the course of different AD biomarkers in the preclinical and clinical stages of autosomal dominant AD. C1 [Fleisher, Adam S.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Fleisher, Adam S.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Fleisher, Adam S.; Chen, Kewei; Langbaum, Jessica B. S.; Roontiva, Auttawut; Thiyyagura, Pradeep; Lee, Wendy; Ayutyanont, Napatkamon; Huentelman, Matthew J.; Tariot, Pierre N.; Reiman, Eric M.] Arizona Alzheimers Consortium, Phoenix, AZ USA. [Fleisher, Adam S.; Chen, Kewei; Jakimovich, Laura J.; Langois, Carolyn M.; Langbaum, Jessica B. S.; Roontiva, Auttawut; Thiyyagura, Pradeep; Lee, Wendy; Ayutyanont, Napatkamon; Tariot, Pierre N.; Reiman, Eric M.] Banner Alzheimers Inst, Phoenix, AZ USA. [Chen, Kewei] Arizona State Univ, Dept Math & Stat, Tempe, AZ USA. [Quiroz, Yakeel T.; Huentelman, Matthew J.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Quiroz, Yakeel T.; Gutierrez Gomez, Madelyn; Lopez, Liliana; Moreno, Sonia; Munoz, Claudia; Tirado, Victoria; Acosta-Baena, Natalia; Giraldo, Margarita; Garcia, Gloria; Lopera, Francisco] Univ Antioquia, Grp Neurociencias, Medellin, Colombia. [Fagan, Anne M.] Washington Univ Sch Med, Dept Neurol, St Louis, MO USA. [Tariot, Pierre N.; Reiman, Eric M.] Univ Arizona, Dept Psychiat, Phoenix, AZ USA. [Reiman, Eric M.] Translat Genom Res Inst, Div Neurogen, Phoenix, AZ USA. RP Fleisher, AS (reprint author), Banner Alzheimers Inst, 901 E Willetta St, Phoenix, AZ 85006 USA. EM adam.fleisher@bannerhealth.com FU Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly and Company); FIL Foundation; Banner Alzheimer's Foundation; Avid Radiopharmaceuticals; Nomis Foundation; Forget Me Not Initiative; Colciencias; Universidad de Antioquia [111554531651]; National Institute on Aging [RO1 AG031581, P30 AG19610, U19 AG03243806, RF1 AG041705, RO1AG041232]; State of Arizona FX 18F-florbetapir positron emission tomography data were acquired with financial support from Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly and Company) as noted in our group's previous study.5 This study was supported by the FIL Foundation, Banner Alzheimer's Foundation, Avid Radiopharmaceuticals, Nomis Foundation, Forget Me Not Initiative, Colciencias, grant 111554531651 from the Universidad de Antioquia, and grants RO1 AG031581, P30 AG19610, U19 AG03243806, RF1 AG041705, and RO1AG041232 from the National Institute on Aging and the State of Arizona. NR 35 TC 21 Z9 21 U1 2 U2 7 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 MAR PY 2015 VL 72 IS 3 BP 316 EP 324 DI 10.1001/jamaneurol.2014.3314 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CE9IJ UT WOS:000352157200012 PM 25580592 ER PT J AU Kaup, AR Nettiksimmons, J Harris, TB Sink, KM Satterfield, S Metti, AL Ayonayon, HN Yaffe, K AF Kaup, Allison R. Nettiksimmons, Jasmine Harris, Tamara B. Sink, Kaycee M. Satterfield, Suzanne Metti, Andrea L. Ayonayon, Hilsa N. Yaffe, Kristine CA Hlth Aging Body Composition Hlth TI Cognitive Resilience to Apolipoprotein E epsilon 4 Contributing Factors in Black and White Older Adults SO JAMA NEUROLOGY LA English DT Article ID ALZHEIMER-DISEASE; AFRICAN-AMERICANS; BODY-COMPOSITION; VARIABLE IMPORTANCE; METABOLIC SYNDROME; RANDOM FORESTS; APOE GENOTYPE; RISK-FACTORS; DEMENTIA; COMMUNITY AB IMPORTANCE Apolipoprotein E (APOE) epsilon 4 is an established risk factor for cognitive decline and the development of dementia, but other factors may help to minimize its effects. OBJECTIVE Using APOE epsilon 4 as an indicator of high risk, we investigated factors associated with cognitive resilience among black and white older adults who are APOE epsilon 4 carriers. DESIGN, SETTING, AND PARTICIPANTS Participants included 2487 community-dwelling older (aged 69-80 years at baseline) black and white adults examined at 2 community clinics in the prospective cohort Health, Aging, and Body Composition (Health ABC) study. The baseline visits occurred from May 1997 through June 1998. Our primary analytic cohort consisted of 670 APOE epsilon 4 carriers (329 black and 341 white participants) who were free of cognitive impairment at baseline and underwent repeated cognitive testing during an 11-year follow-up (through 2008) using the Modified Mini-Mental State Examination. MAIN OUTCOMES AND MEASURES We stratified all analyses by race. Using the Modified Mini-Mental State Examination scores, we assessed normative cognitive change in the entire cohort (n = 2487) and classified the APOE epsilon 4 carriers as being cognitively resilient vs nonresilient by comparing their cognitive trajectories with those of the entire cohort. We then conducted bivariate analyses and multivariable random forest and logistic regression analyses to explore factors predictive of cognitive resilience in APOE epsilon 4 carriers. RESULTS Among white APOE epsilon 4 carriers, the strongest predictors of cognitive resilience were, in relative order of importance, no recent negative life events, a higher literacy level, advanced age, a higher educational level, and more time spent reading. Among black APOE epsilon 4 carriers, the strongest predictors of cognitive resilience were, in relative order of importance, a higher literacy level, a higher educational level, female sex, and the absence of diabetes mellitus. In follow-up logistic regression models, higher literacy level (adjusted odds ratio [OR], 9.50 [95% CI, 2.67-60.89]), a higher educational level (adjusted OR for college graduate vs less than high school, 3.81 [95% CI, 1.13-17.56]), and age (adjusted OR for 73-76 vs 69-72 years, 2.01 [95% CI, 1.13-3.63]) had significant independent effects in predicting cognitive resilience among white APOE epsilon 4 carriers. Among black APOE epsilon 4 carriers, a higher literacy level (adjusted OR, 2.27 [95% CI, 1.29-4.06]) and a higher educational level (adjusted OR for high school graduate/some college vs less than high school, 2.86 [95% CI, 1.54-5.49]; adjusted OR for college graduate vs less than high school, 2.52 [95% CI, 1.14-5.62]) had significant independent effects in predicting cognitive resilience. CONCLUSIONS AND RELEVANCE Although APOE epsilon 4 carriers are at high risk for cognitive decline, our findings suggest possible intervention targets, including the enhancement of cognitive reserve and improvement of other psychosocial and health factors, to promote cognitive resilience among black and white APOE epsilon 4 carriers. C1 [Kaup, Allison R.; Yaffe, Kristine] San Francisco VA Med Ctr, Sierra Pacific Mental Illness Res Educ & Clin Ctr, San Francisco, CA 94121 USA. [Kaup, Allison R.; Nettiksimmons, Jasmine; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Bethesda, MD 20892 USA. [Sink, Kaycee M.] Wake Forest Sch Med, Dept Med, Sect Gerontol & Geriatr Med, Winston Salem, NC USA. [Satterfield, Suzanne] Univ Tennessee Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Metti, Andrea L.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Ayonayon, Hilsa N.; Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. RP Kaup, AR (reprint author), San Francisco VA Med Ctr, Sierra Pacific Mental Illness Res Educ & Clin Ctr, 4150 Clement St,Mail Code T16H, San Francisco, CA 94121 USA. EM allison.kaup@ucsf.edu FU NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050, K24AG031155]; National Institute on Nursing Research [R01-NR012459]; NIA/NIH; Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment; Medical Research Service of the San Francisco Veterans Affairs Medical Center; Sierra Pacific Mental Illness Research, Education, and Clinical Center FX This study was supported by contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106 and grant R01-AG028050 from the NIA; by grant R01-NR012459 from the National Institute on Nursing Research; and in part by the Intramural Research Program of the NIA/NIH, all of which supported the design and conduct of the study; collection, management, analysis, and interpretation of the data; and review and approval of the manuscript. This study was also supported by grant K24AG031155 from the NIA (Dr Yaffe), which supported the design and conduct of the study, analysis and interpretation of the data, preparation and review of the manuscript, and decision to submit the manuscript for publication. Preparation of the manuscript was supported by the Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment, the Medical Research Service of the San Francisco Veterans Affairs Medical Center, and the Sierra Pacific Mental Illness Research, Education, and Clinical Center. NR 38 TC 5 Z9 5 U1 1 U2 5 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 MAR PY 2015 VL 72 IS 3 BP 340 EP 348 DI 10.1001/jamaneurol.2014.3978 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CE9IJ UT WOS:000352157200015 PM 25599330 ER PT J AU Etherton, MR Neagu, MR Oakley, DH Koch, MJ Shin, JH Frosch, MP Berkowitz, AL Dietrich, J AF Etherton, Mark R. Neagu, Martha R. Oakley, Derek H. Koch, Matthew J. Shin, John H. Frosch, Matthew P. Berkowitz, Aaron L. Dietrich, Jorg TI A 20-Year-Old Man With Back Pain and Lower Extremity Weakness SO JAMA NEUROLOGY LA English DT Article ID SPINAL-CORD TUMORS; GLIOBLASTOMA-MULTIFORME; MYELITIS AB A 20-year-old man presented with 1 week of low back pain and progressive lower extremity weakness. Results of cerebrospinal fluid analysis demonstrated elevated total protein and a mildly elevated white blood cell count with lymphocytic predominance. Findings from imaging studies revealed a multifocal, heterogeneously enhancing, intramedullary lesion involving the cervicothoracic spinal cord and nodular enhancement of the cauda equina. The patient eventually underwent spinal surgery for tissue diagnosis. The differential diagnosis, pathologic findings, and diagnosis are discussed. C1 [Etherton, Mark R.; Neagu, Martha R.; Dietrich, Jorg] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Etherton, Mark R.; Neagu, Martha R.; Berkowitz, Aaron L.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Etherton, Mark R.; Neagu, Martha R.; Oakley, Derek H.; Koch, Matthew J.; Shin, John H.; Frosch, Matthew P.; Berkowitz, Aaron L.; Dietrich, Jorg] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Oakley, Derek H.; Frosch, Matthew P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Koch, Matthew J.; Shin, John H.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Dietrich, Jorg] Massachusetts Gen Hosp, Div Neurooncol, Boston, MA 02114 USA. RP Etherton, MR (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,WACC 720, Boston, MA 02114 USA. EM metherton@partners.org NR 14 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD MAR PY 2015 VL 72 IS 3 BP 363 EP 366 DI 10.1001/jamaneurol.2014.3833 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA CE9IJ UT WOS:000352157200018 PM 25621865 ER PT J AU Sakanaka, T Inoue, T Yorifuji, N Iguchi, M Fujiwara, K Narabayashi, K Kakimoto, K Nouda, S Okada, T Kuramoto, T Ishida, K Abe, Y Takeuchi, T Umegaki, E Akiba, Y Kaunitz, JD Higuchi, K AF Sakanaka, Taisuke Inoue, Takuya Yorifuji, Naoki Iguchi, Munetaka Fujiwara, Kaori Narabayashi, Ken Kakimoto, Kazuki Nouda, Sadaharu Okada, Toshihiko Kuramoto, Takanori Ishida, Kumi Abe, Yosuke Takeuchi, Toshihisa Umegaki, Eiji Akiba, Yasutada Kaunitz, Jonathan D. Higuchi, Kazuhide TI The effects of a TGR5 agonist and a dipeptidyl peptidase IV inhibitor on dextran sulfate sodium-induced colitis in mice SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article; Proceedings Paper CT 15th Taishotoyama International Symposium on Gastroenterology CY SEP 26-28, 2013 CL Tokyo, JAPAN DE dextran sulfate sodium; DPPIV; GLP-2; sitagliptin; TGR5 ID L CELLS; EXPRESSION; SECRETION; ACID; LOCALIZATION; RAT AB Background and AimLuminal nutrients stimulate enteroendocrine L cells to release gut hormones, including intestinotrophic glucagon-like peptide-2 (GLP-2). Because L cells express the bile acid receptor TGR5 and dipeptidyl peptidase-IV (DPPIV) rapidly degrades GLPs, we hypothesized that luminal TGR5 activation may attenuate intestinal injury via GLP-2 release, which is enhanced by DPPIV inhibition. MethodsIntestinal injury was induced in mice by administration of dextran sulfate sodium (DSS) in drinking water (free access to water containing 5% DSS for 7 days). The selective TGR5 agonist betulinic acid (BTA) and the DPPIV inhibitor sitagliptin phosphate monohydrate (STG) were administered orally for 7 days. Male C57BL/6 mice (6-7 weeks old) were divided into five groups: normal control group, disease control group, BTA low group (drinking water containing 15mg/L BTA), BTA high group (50mg/L BTA), and BTA high+STG (3mg/kg, i.g.) group. ResultsThe selective TGR5 agonist BTA dose-dependently suppressed disease activity index and mRNA expression of the pro-inflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor- in the colon. Nevertheless, STG administration had little additive effect on BTA-induced protection. Fibroblast activation protein mRNA expression, but not expression of other DPP family members, was increased in the colon of DSS-treated mice with increased mucosal DPPIV. Co-administration of the selective GLP-2 antagonist GLP-2 (3-33) reversed the effect of BTA. ConclusionThe selective TGR5 agonist BTA ameliorated DSS-induced colitis in mice via the GLP-2 pathway with no effect of DPPIV inhibition, suggesting that other DPP enzymatic activity is involved in GLP-2 degradation. C1 [Sakanaka, Taisuke; Inoue, Takuya; Yorifuji, Naoki; Iguchi, Munetaka; Fujiwara, Kaori; Narabayashi, Ken; Kakimoto, Kazuki; Nouda, Sadaharu; Okada, Toshihiko; Kuramoto, Takanori; Ishida, Kumi; Abe, Yosuke; Takeuchi, Toshihisa; Umegaki, Eiji; Higuchi, Kazuhide] Osaka Med Coll, Dept Internal Med 2, Takatsuki, Osaka 5698686, Japan. [Akiba, Yasutada; Kaunitz, Jonathan D.] Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. EM ureuretakuwan@yahoo.co.jp FU Intramural VA [VA999999]; NIDDK NIH HHS [R01 DK054221, P30 DK041301] NR 27 TC 5 Z9 5 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0815-9319 EI 1440-1746 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD MAR PY 2015 VL 30 SU 1 SI SI BP 60 EP 65 DI 10.1111/jgh.12740 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CF0IU UT WOS:000352227600013 PM 25827806 ER PT J AU Fung, V Price, M Busch, AB Nierenberg, A Landrum, MB Ongur, D Newhouse, JP Hsu, J AF Fung, Vicki Price, Mary Busch, Alisa B. Nierenberg, Andrew Landrum, Mary Beth Ongur, Dost Newhouse, Joseph P. Hsu, John TI Medicare Mental Health Cost-sharing Parity and Quality of Care for Beneficiaries with Schizophrenia SO JOURNAL OF MENTAL HEALTH POLICY AND ECONOMICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT CTR MENTAL HEALTH POLICY & ECONOMICS-ICMPE PI MILANO PA VIA DANIELE CRESPI 7, MILANO, 20123, ITALY SN 1091-4358 J9 J MENT HEALTH POLICY JI J. Ment. Health Policy Econ. PD MAR PY 2015 VL 18 SU 1 BP S14 EP S14 PG 1 WC Health Policy & Services; Psychiatry SC Health Care Sciences & Services; Psychiatry GA CF4LX UT WOS:000352521700029 ER PT J AU Hodgkin, D Merrick, EL O'Brien, P Lee, S Deckersbach, T Nierenberg, AA AF Hodgkin, Dominic Merrick, Elizabeth L. O'Brien, Peggy Lee, Sue Deckersbach, Thilo Nierenberg, Andrew A. TI The Extent and Predictors of Clinical Inertia in Medication Treatment of Bipolar Disorder SO JOURNAL OF MENTAL HEALTH POLICY AND ECONOMICS LA English DT Meeting Abstract C1 [Hodgkin, Dominic; Merrick, Elizabeth L.; O'Brien, Peggy; Lee, Sue] Brandeis Univ, Heller Sch Social Policy & Management, Inst Behav Hlth, Waltham, MA USA. [Deckersbach, Thilo; Nierenberg, Andrew A.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU INT CTR MENTAL HEALTH POLICY & ECONOMICS-ICMPE PI MILANO PA VIA DANIELE CRESPI 7, MILANO, 20123, ITALY SN 1091-4358 J9 J MENT HEALTH POLICY JI J. Ment. Health Policy Econ. PD MAR PY 2015 VL 18 SU 1 BP S21 EP S21 PG 1 WC Health Policy & Services; Psychiatry SC Health Care Sciences & Services; Psychiatry GA CF4LX UT WOS:000352521700044 ER PT J AU Hsu, J Huang, J Fireman, B Singer, D Ongur, D Fang, V AF Hsu, John Huang, Jie Fireman, Bruce Singer, Danny Ongur, Dost Fang, Vicki TI Adherence to Psychotropic and Medical Therapy among Patients with Severe Mental Illnesses: Being of Two Minds? SO JOURNAL OF MENTAL HEALTH POLICY AND ECONOMICS LA English DT Meeting Abstract C1 [Hsu, John; Huang, Jie; Fireman, Bruce; Singer, Danny; Ongur, Dost; Fang, Vicki] Harvard Univ, Massachusetts Gen Hosp, McLean Hosp, Sch Med,Kaiser Fdn Res Inst, Cambridge, MA 02138 USA. FU [R01MH090284]; [R01MH104560] FX R01MH090284, R01MH104560. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT CTR MENTAL HEALTH POLICY & ECONOMICS-ICMPE PI MILANO PA VIA DANIELE CRESPI 7, MILANO, 20123, ITALY SN 1091-4358 J9 J MENT HEALTH POLICY JI J. Ment. Health Policy Econ. PD MAR PY 2015 VL 18 SU 1 BP S22 EP S23 PG 2 WC Health Policy & Services; Psychiatry SC Health Care Sciences & Services; Psychiatry GA CF4LX UT WOS:000352521700046 ER PT J AU Hsu, J Price, M Ongur, D Busch, A New-House, J Fung, V AF Hsu, John Price, Maggie Ongur, Dost Busch, Alisa New-house, Joseph Fung, Vicki TI Whither and To Whom Must I Wander: Geographic Distribution of Mental Health Provider Supply and the Role of Non-Physician Providers SO JOURNAL OF MENTAL HEALTH POLICY AND ECONOMICS LA English DT Meeting Abstract C1 [Hsu, John; Price, Maggie; Ongur, Dost; Busch, Alisa; New-house, Joseph; Fung, Vicki] Harvard Univ, Massachusetts Gen Hosp, McLean Hosp, Sch Med, Cambridge, MA 02138 USA. FU [R01MH090284]; [R01MH104560]; [P01AG032952] FX R01MH090284, R01MH104560, P01AG032952. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT CTR MENTAL HEALTH POLICY & ECONOMICS-ICMPE PI MILANO PA VIA DANIELE CRESPI 7, MILANO, 20123, ITALY SN 1091-4358 J9 J MENT HEALTH POLICY JI J. Ment. Health Policy Econ. PD MAR PY 2015 VL 18 SU 1 BP S23 EP S23 PG 1 WC Health Policy & Services; Psychiatry SC Health Care Sciences & Services; Psychiatry GA CF4LX UT WOS:000352521700047 ER PT J AU Eaton, JL Mohr, DC Gallarde, S Hodgson, MJ AF Eaton, Jennifer L. Mohr, David C. Gallarde, Sheryl Hodgson, Michael J. TI Impact of Clinical Quality on Employee Choice of Providers for Workers' Compensation-Related Medical Care SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID SPECIALTY BOARD CERTIFICATION; HEALTH-CARE; OCCUPATIONAL-MEDICINE; COST; OUTCOMES; PROGRAM; RETURN AB Objective: The study examined the relationship between onsite occupational health practice characteristics, provider choice, and workers' compensation outcome metrics. Methods: Cross-sectional survey of 140 medical center occupational health clinics within the Department of Veterans Affairs. Multivariate regression models examined how specific clinical quality factors influenced provider choice and workers' compensation measures. Results: Several practice characteristics were associated with higher rates of in-house care selection-longer hours of operation, greater availability of workers' compensation-related medical services, clinic administration by a board certified physician, physician tenure, and adherence to clinical practice guidelines. Access to onsite, occupational and environmental medicine certified physician-directed care was associated with reductions in disability duration among injured healthcare workers. Conclusions: These findings suggest that occupational medicine board certification can positively impact provider choice among fully insured patients, which may have implications for other healthcare systems. C1 [Eaton, Jennifer L.] Vet Hlth Adm, Off Publ Hlth, Occupat Hlth Grp, Washington, DC 20006 USA. [Eaton, Jennifer L.] VA Med Ctr, War Related Illness & Injury Study Ctr, Washington, DC USA. [Mohr, David C.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Dept Vet Affairs, Boston, MA USA. [Mohr, David C.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02215 USA. [Gallarde, Sheryl] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Eaton, JL (reprint author), Vet Hlth Adm, Off Publ Hlth, Occupat Hlth Grp, 1717 H St NW Rm 504, Washington, DC 20006 USA. EM Jennifer.Lipkowitz-Eaton@va.gov FU Veterans Health Administration FX This work was supported by operational funds in the Veterans Health Administration. NR 27 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD MAR PY 2015 VL 57 IS 3 SU S BP S31 EP S35 DI 10.1097/JOM.0000000000000387 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CF4GO UT WOS:000352507000006 PM 25741612 ER PT J AU Turner, PV Pekow, C Clark, JM Vergara, P Bayne, K White, WJ Kurosawa, TM Seok, SH Baneux, P AF Turner, Patricia V. Pekow, Cynthia Clark, Judy MacArthur Vergara, Patri Bayne, Kathryn White, William J. Kurosawa, Tsutomu Miki Seok, Seung-Hyeok Baneux, Philippe TI Roles of the International Council for Laboratory Animal Science (ICLAS) and International Association of Colleges of Laboratory Animal Medicine (IACLAM) in the Global Organization and Support of 3Rs Advances in Laboratory Animal Science SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID VETERINARY-CARE; HARMONIZATION; GUIDELINES; NEEDS AB Practical implementation of the 3Rs at national and regional levels around the world requires long-term commitment, backing, and coordinated efforts by international associations for laboratory animal medicine and science, including the International Association of Colleges of Laboratory Animal Medicine (IACLAM) and the International Council for Laboratory Animal Science (ICLAS). Together these organizations support the efforts of regional organization and communities of laboratory animal science professionals as well as the development of local associations and professional colleges that promote the training and continuing education of research facility personnel and veterinary specialists. The recent formation of a World Organization for Animal Health (OIE) Collaborating Center for Laboratory Animal Science and Welfare emphasizes the need for research into initiatives promoting laboratory animal welfare, particularly in emerging economies and regions with nascent associations of laboratory animal science. C1 [Turner, Patricia V.] Univ Guelph, Dept Pathobiol, Guelph, ON N1G 2W1, Canada. [Pekow, Cynthia] Vet Affairs Puget Sound Hlth Care Syst, Res & Dev, Seattle, WA USA. [Clark, Judy MacArthur] Home Off, Anim Sci Regulat Unit, London, England. [Vergara, Patri] Autonomous Univ Barcelona, Fac Vet Med, Physiol Unit, Barcelona, Spain. [Bayne, Kathryn] Assoc Assessment & Accreditat Lab Anim Care Int, Frederick, MD USA. [White, William J.] Charles River, Vet & Profess Serv, Wilmington, MA USA. [Kurosawa, Tsutomu Miki] Osaka Univ, Inst Expt Anim Sci, Dept Lab Anim Med, Osaka, Japan. [Seok, Seung-Hyeok] Seoul Natl Univ, Dept Microbiol & Immunol, Seoul, South Korea. [Baneux, Philippe] Cornell Univ, Cornell Ctr Anim Resources & Educ, Ithaca, NY USA. RP Turner, PV (reprint author), Univ Guelph, Dept Pathobiol, Guelph, ON N1G 2W1, Canada. EM pvturner@uoguelph.ca RI Vergara, Patrocinio/M-6468-2013 OI Vergara, Patrocinio/0000-0002-9220-6406 NR 22 TC 3 Z9 3 U1 0 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD MAR PY 2015 VL 54 IS 2 BP 174 EP 180 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA CE8UJ UT WOS:000352119300009 PM 25836964 ER PT J AU Friedlander, AH Hazboun, RC AF Friedlander, Arthur H. Hazboun, Renna C. TI ANTIBIOTICS AND IMPLANTS SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Editorial Material C1 [Friedlander, Arthur H.] VA Greater Los Angeles Healthcare Syst, Grad Med Educ, Los Angeles, CA 90073 USA. [Friedlander, Arthur H.] Univ Calif Los Angeles, Sch Dent, Hosp Dent Serv, Oral & Maxillofacial Surg, Los Angeles, CA USA. [Friedlander, Arthur H.] Univ Calif Los Angeles, Sch Dent, Hosp Dent Serv, Qual Assurance, Los Angeles, CA USA. [Friedlander, Arthur H.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. [Hazboun, Renna C.] VA Greater Los Angeles Healthcare Syst, Oral & Maxillofacial Surg Res, Los Angeles, CA USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, Grad Med Educ, Los Angeles, CA 90073 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 EI 1943-4723 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD MAR PY 2015 VL 146 IS 3 BP 146 EP 146 DI 10.1016/j.adaj.2015.01.008 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CE9GR UT WOS:000352152600006 PM 25726341 ER PT J AU Tierney, ESS Gauvreau, K Jaff, MR Gal, D Nourse, SE Trevey, S O'Neill, S Baker, A Newburger, JW Colan, SD AF Tierney, Elif Seda Selamet Gauvreau, Kimberlee Jaff, Michael R. Gal, Dana Nourse, Susan E. Trevey, Shari O'Neill, Stephen Baker, Annette Newburger, Jane W. Colan, Steven D. TI Carotid Artery Intima-Media Thickness Measurements in the Youth: Reproducibility and Technical Considerations SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Carotid artery IMT; Youth; Reproducibility; Variability; Carotid artery ultrasound; Atherosclerosis ID LOW-DENSITY-LIPOPROTEIN; FAMILIAL HYPERCHOLESTEROLEMIA; WALL THICKNESS; ENDOTHELIAL DYSFUNCTION; YOUNG-ADULTS; RISK-FACTORS; CHILDREN; DISEASE; ATHEROSCLEROSIS; PROGRESSION AB Background: Carotid artery intima-media thickness (CIMT), a marker of atherosclerosis, is increased in youth at risk for future cardiovascular disease. Some pediatric studies have used CIMT as a primary outcome in clinical trials, yet data are limited on the standardization of methodology in children. The goal of this study was to evaluate reproducibility of CIMT measurements using two different measurement techniques. Methods: Carotid artery ultrasound studies of children and adolescents obtained as a component of a research study in Kawasaki syndrome were retrospectively analyzed. The CIMTs of both common carotid arteries (CCAs) were measured by one of two sonographers at the time in the cardiac cycle when resolution subjectively was determined to be optimal (Opt-CIMT). These sonographers blindly remeasured a random sample of studies of their own and each other's, using the same method. Another observer made CIMT measurements using exclusively frames on the R wave (R-CIMT). A fourth observer independently measured a random sample of studies twice with the R-CIMT method. Results: Carotid artery images from 184 subjects (mean age, 14.7 +/- 2.2 years) were analyzed. The intraclass correlation coefficient for interobserver variability was 0.86 (95% confidence interval [CI], 0.69-0.94) compared with 0.85 (95% CI, 0.65-0.93) for the right and 0.86 (95% CI, 0.67-0.94) versus 0.95 (95% CI, 0.87-0.98) for the left CCA for Opt-CIMT and R-CIMT, respectively. R-CIMT was significantly thicker than Opt-CIMT (right CCA, 0.439 +/- 0.030 vs 0.428 +/- 0.024 mm, P < .001; left CCA, 0.446 +/- 0.030 vs 0.434 +/- 0.025 mm, P < .001). Conclusion: Pediatric CIMT measurements have excellent reproducibility when the same methodology is applied but vary significantly throughout the cardiac cycle. This report highlights the need to standardize CIMT measurements in the youth and supports the use of electrocardiographic timing, as recommended in adults, in pediatric longitudinal studies. C1 [Tierney, Elif Seda Selamet; Gauvreau, Kimberlee; Gal, Dana; Trevey, Shari; O'Neill, Stephen; Baker, Annette; Newburger, Jane W.; Colan, Steven D.] Childrens Hosp Boston, Dept Cardiol, Boston, MA USA. [Tierney, Elif Seda Selamet; Gauvreau, Kimberlee; Gal, Dana; Trevey, Shari; O'Neill, Stephen; Baker, Annette; Newburger, Jane W.; Colan, Steven D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Tierney, Elif Seda Selamet; Nourse, Susan E.] Stanford Univ, Div Pediat Cardiol, Dept Pediat, Palo Alto, CA 94304 USA. [Jaff, Michael R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiol, Boston, MA USA. RP Tierney, ESS (reprint author), Stanford Univ, Pediat Heart Ctr, 750 Welch Rd,Suite 350,Mail Code 5731, Palo Alto, CA 94304 USA. EM tierneys@stanford.edu OI Colan, Steven/0000-0002-7941-0947 FU American Heart Association; National Scientist Development Award; Farb and McCance Family Funds FX This study was supported by the American Heart Association, a National Scientist Development Award, and the Farb and McCance Family Funds. NR 41 TC 5 Z9 6 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD MAR PY 2015 VL 28 IS 3 BP 309 EP 316 DI 10.1016/j.echo.2014.10.004 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE9DR UT WOS:000352144400007 ER PT J AU Niederst, MJ Sequist, LV Poirier, JT Mermel, CH Lockerman, EL Garcia, AR Katayama, R Costa, C Ross, KN Moran, T Howe, E Fulton, LE Mulvey, HE Bernardo, LA Mohamoud, F Miyoshi, N VanderLaan, PA Costa, DB Janne, PA Borger, DR Ramaswamy, S Shioda, T Iafrate, AJ Getz, G Rudin, CM Mino-Kenudson, M Engelman, JA AF Niederst, Matthew J. Sequist, Lecia V. Poirier, John T. Mermel, Craig H. Lockerman, Elizabeth L. Garcia, Angel R. Katayama, Ryohei Costa, Carlotta Ross, Kenneth N. Moran, Teresa Howe, Emily Fulton, Linnea E. Mulvey, Hillary E. Bernardo, Lindsay A. Mohamoud, Farhiya Miyoshi, Norikatsu VanderLaan, Paul A. Costa, Daniel B. Jaenne, Pasi A. Borger, Darrell R. Ramaswamy, Sridhar Shioda, Toshi Iafrate, Anthony J. Getz, Gad Rudin, Charles M. Mino-Kenudson, Mari Engelman, Jeffrey A. TI RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer SO NATURE COMMUNICATIONS LA English DT Article ID GROWTH-FACTOR RECEPTOR; ACQUIRED-RESISTANCE; KINASE INHIBITORS; DRUG-SENSITIVITY; MUTATION; GEFITINIB; AMPLIFICATION; CHEMOTHERAPY; MODELS; GENE AB Tyrosine kinase inhibitors are effective treatments for non-small-cell lung cancers (NSCLCs) with epidermal growth factor receptor (EGFR) mutations. However, relapse typically occurs after an average of 1 year of continuous treatment. A fundamental histological transformation from NSCLC to small-cell lung cancer (SCLC) is observed in a subset of the resistant cancers, but the molecular changes associated with this transformation remain unknown. Analysis of tumour samples and cell lines derived from resistant EGFR mutant patients revealed that Retinoblastoma (RB) is lost in 100% of these SCLC transformed cases, but rarely in those that remain NSCLC. Further, increased neuroendocrine marker and decreased EGFR expression as well as greater sensitivity to BCL2 family inhibition are observed in resistant SCLC transformed cancers compared with resistant NSCLCs. Together, these findings suggest that this subset of resistant cancers ultimately adopt many of the molecular and phenotypic characteristics of classical SCLC. C1 [Niederst, Matthew J.; Sequist, Lecia V.; Lockerman, Elizabeth L.; Garcia, Angel R.; Katayama, Ryohei; Costa, Carlotta; Ross, Kenneth N.; Moran, Teresa; Howe, Emily; Fulton, Linnea E.; Mulvey, Hillary E.; Mohamoud, Farhiya; Borger, Darrell R.; Ramaswamy, Sridhar; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Niederst, Matthew J.; Sequist, Lecia V.; Lockerman, Elizabeth L.; Garcia, Angel R.; Katayama, Ryohei; Costa, Carlotta; Ross, Kenneth N.; Moran, Teresa; Howe, Emily; Fulton, Linnea E.; Mulvey, Hillary E.; Mohamoud, Farhiya; Miyoshi, Norikatsu; Borger, Darrell R.; Ramaswamy, Sridhar; Shioda, Toshi; Getz, Gad; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Poirier, John T.; Rudin, Charles M.] Mem Sloan Kettering Canc Ctr, Thorac Oncol Serv, New York, NY 10065 USA. [Mermel, Craig H.; Ramaswamy, Sridhar; Getz, Gad] Broad Inst MIT & Harvard, Canc Genome Comparat Anal Grp, Cambridge, MA 02142 USA. [Mermel, Craig H.; Bernardo, Lindsay A.; Iafrate, Anthony J.; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Ctr Canc, Dept Pathol, Boston, MA 02114 USA. [Bernardo, Lindsay A.; Iafrate, Anthony J.; Mino-Kenudson, Mari] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Miyoshi, Norikatsu; Shioda, Toshi] Massachusetts Gen Hosp, Ctr Canc, Mol Profiling Lab, Boston, MA 02114 USA. [VanderLaan, Paul A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Costa, Daniel B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Div Hematol Oncol, Boston, MA 02115 USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Sci, Dept Med Oncol, Boston, MA 02215 USA. [Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Jaenne, Pasi A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Engelman, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM jengelman@mgh.harvard.edu OI Rudin, Charles/0000-0001-5204-3465; Costa, Daniel/0000-0002-0689-395X; Poirier, John/0000-0001-9795-5644; VanderLaan, Paul/0000-0002-7234-5652 FU Lung Cancer Research Foundation; Uniting Against Lung Cancer; NIH/National Cancer Institute [R01CA137008, 5R21CA156000, P50CA090578]; Lungevity; Department of Defense (CDMRP) [LC130190]; Targeting a Cure for Lung Cancer; Piece of the Solution; MGH Thoracic Oncology Group FX We thank Dr Nick Dyson for the constructs targeting GFP and RB and Dr James Rocco and Dr William Michaud for supplying feeder cells and helpful advice. This work was supported by the Lung Cancer Research Foundation (Scientific Merit Award, M.J.N.), Uniting Against Lung Cancer (L.V.S. and M.J.N.), NIH/National Cancer Institute (R01CA137008, J.A.E., 5R21CA156000, L.V.S. and P50CA090578, D.B.C.), Lungevity (J.A.E. and L.V.S.) Department of Defense (CDMRP LC130190, C.M.R and P.A.J.) and philanthropic support from Targeting a Cure for Lung Cancer, Be a Piece of the Solution, and the MGH Thoracic Oncology Group. NR 37 TC 52 Z9 53 U1 2 U2 16 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 MAR PY 2015 VL 6 AR UNSP 6377 DI 10.1038/ncomms7377 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF5YK UT WOS:000352633100002 PM 25758528 ER PT J AU van Leeuwen, EM Karssen, LC Deelen, J Isaacs, A Medina-Gomez, C Mbarek, H Kanterakis, A Trompet, S Postmus, I Verweij, N van Enckevort, DJ Huffman, JE White, CC Feitosa, MF Bartz, TM Manichaikul, A Joshi, PK Peloso, GM Deelen, P van Dijk, F Willemsen, G de Geus, EJ Milaneschi, Y Penninx, BWJH Francioli, LC Menelaou, A Pulit, SL Rivadeneira, F Hofman, A Oostra, BA Franco, OH Leach, IM Beekman, M de Craen, AJM Uh, HW Trochet, H Hocking, LJ Porteous, DJ Sattar, N Packard, CJ Buckley, BM Brody, JA Bis, JC Rotter, JI Mychaleckyj, JC Campbell, H Duan, Q Lange, LA Wilson, JF Hayward, C Polasek, O Vitart, V Rudan, I Wright, AF Rich, SS Psaty, BM Borecki, IB Kearney, PM Stott, DJ Cupples, LA Jukema, JW van der Harst, P Sijbrands, EJ Hottenga, JJ Uitterlinden, AG Swertz, MA van Ommen, GJB de Bakker, PIW Slagboom, PE Boomsma, DI Wijmenga, C van Duijn, CM AF van Leeuwen, Elisabeth M. Karssen, Lennart C. Deelen, Joris Isaacs, Aaron Medina-Gomez, Carolina Mbarek, Hamdi Kanterakis, Alexandros Trompet, Stella Postmus, Iris Verweij, Niek van Enckevort, David J. Huffman, Jennifer E. White, Charles C. Feitosa, Mary F. Bartz, Traci M. Manichaikul, Ani Joshi, Peter K. Peloso, Gina M. Deelen, Patrick van Dijk, Freerk Willemsen, Gonneke de Geus, Eco J. Milaneschi, Yuri Penninx, Brenda W. J. H. Francioli, Laurent C. Menelaou, Androniki Pulit, Sara L. Rivadeneira, Fernando Hofman, Albert Oostra, Ben A. Franco, Oscar H. Leach, Irene Mateo Beekman, Marian de Craen, Anton J. M. Uh, Hae-Won Trochet, Holly Hocking, Lynne J. Porteous, David J. Sattar, Naveed Packard, Chris J. Buckley, Brendan M. Brody, Jennifer A. Bis, Joshua C. Rotter, Jerome I. Mychaleckyj, Josyf C. Campbell, Harry Duan, Qing Lange, Leslie A. Wilson, James F. Hayward, Caroline Polasek, Ozren Vitart, Veronique Rudan, Igor Wright, Alan F. Rich, Stephen S. Psaty, Bruce M. Borecki, Ingrid B. Kearney, Patricia M. Stott, David J. Cupples, L. Adrienne Jukema, J. Wouter van der Harst, Pim Sijbrands, Eric J. Hottenga, Jouke-Jan Uitterlinden, Andre G. Swertz, Morris A. van Ommen, Gert-Jan B. de Bakker, Paul I. W. Slagboom, P. Eline Boomsma, Dorret I. Wijmenga, Cisca van Duijn, Cornelia M. CA Genome Netherlands Consortium TI Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels SO NATURE COMMUNICATIONS LA English DT Article ID WIDE ASSOCIATION; MUTATIONS; DISEASE AB Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (similar to 35,000 samples) with the population-specific reference panel created by the Genome of the Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value < 6.61 x 10(-4)), including a rare missense variant in ABCA6 (rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted to be deleterious. The frequency of this ABCA6 variant is 3.65-fold increased in the Dutch and its effect (beta(LDL-C) = 0.135, beta(TC) = 0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as LDLR. C1 [van Leeuwen, Elisabeth M.; Karssen, Lennart C.; Isaacs, Aaron; Hofman, Albert; Franco, Oscar H.; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Deelen, Joris; Beekman, Marian; Slagboom, P. Eline] Leiden Univ, Med Ctr, Dept Mol Epidemiol, NL-2300 RC Leiden, Netherlands. [Medina-Gomez, Carolina; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol & Internal Med, NL-3000 CA Rotterdam, Netherlands. [Mbarek, Hamdi; Willemsen, Gonneke; de Geus, Eco J.; Hottenga, Jouke-Jan] Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands. [Mbarek, Hamdi; Willemsen, Gonneke; de Geus, Eco J.; Hottenga, Jouke-Jan] EMGO, Inst Hlth & Care Res, NL-1081 BT Amsterdam, Netherlands. [Kanterakis, Alexandros; Deelen, Patrick; van Dijk, Freerk; Swertz, Morris A.] Univ Groningen, Univ Med Ctr Groningen, Dept Genet Genom Coordinat Ctr, NL-9700 RB Groningen, Netherlands. [Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands. [Postmus, Iris] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2300 RC Leiden, Netherlands. [Verweij, Niek] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands. [van Enckevort, David J.] BioAssist, Netherlands Bioinformat Ctr, NL-6500 HB Nijmegen, Netherlands. [Huffman, Jennifer E.; Trochet, Holly; Hayward, Caroline; Vitart, Veronique; Wright, Alan F.] Univ Edinburgh, MRC Human Genet Unit, MRC IGMM, Edinburgh EH4 2XU, Midlothian, Scotland. [White, Charles C.; Cupples, L. Adrienne] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02118 USA. [Feitosa, Mary F.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63108 USA. [Bartz, Traci M.] Univ Washington, Dept Biostat & Med, Seattle, WA 98101 USA. [Manichaikul, Ani; Mychaleckyj, Josyf C.; Rich, Stephen S.] Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA. [Joshi, Peter K.; Campbell, Harry; Wilson, James F.; Rudan, Igor] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland. [Peloso, Gina M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02176 USA. [Milaneschi, Yuri; Penninx, Brenda W. J. H.; de Craen, Anton J. M.] Vrije Univ Amsterdam, Dept Psychiat, Med Ctr Amsterdam,Neurosci Campus Amsterdam, GGZinGeest,EMGO,Inst Hlth & Care Res, NL-1081 HL Amsterdam, Netherlands. [Francioli, Laurent C.; Menelaou, Androniki; Pulit, Sara L.; de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet, Ctr Mol Med, NL-3584 CG Utrecht, Netherlands. [Oostra, Ben A.] Erasmus MC, Dept Clin Genet, NL-3000 CA Rotterdam, Netherlands. [Uh, Hae-Won] Leiden Univ, Med Ctr, Dept Genet Stat, NL-2300 RC Leiden, Netherlands. [Hocking, Lynne J.] Univ Aberdeen, Div Appl Hlth Sci, Aberdeen AB25 2ZD, Scotland. [Porteous, David J.] Univ Edinburgh, Ctr Genom & Expt Med, MRC IGMM, Edinburgh EH4 2XU, Midlothian, Scotland. [Sattar, Naveed] Univ Glasgow, Fac Med, BHF Glasgow Cardiovasc Res Ctr, Glasgow G12 8QQ, Lanark, Scotland. [Packard, Chris J.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8QQ, Lanark, Scotland. [Buckley, Brendan M.] Univ Coll, Dept Pharmacol & Therapeut, Cork, Ireland. [Brody, Jennifer A.; Bis, Joshua C.] Univ Washington, Dept Med, Seattle, WA 98101 USA. [Rotter, Jerome I.] UCLA, Inst Translat Genom & Populat Sci, Los Angeles BioMed Res Inst Harbor, Med Ctr, Torrance, CA 90502 USA. [Duan, Qing; Lange, Leslie A.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Polasek, Ozren] Univ Split, Fac Med, Dept Publ Hlth, Split 21000, Croatia. [Psaty, Bruce M.] Univ Washington, Dept Med & Epidemiol, Seattle, WA 98101 USA. [Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet & Biostat, St Louis, MO 63108 USA. [Cupples, L. Adrienne] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Sijbrands, Eric J.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [van Ommen, Gert-Jan B.] Leiden Univ, Med Ctr, Dept Human Genet, NL-2300 RC Leiden, Netherlands. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, NL-3584 CG Utrecht, Netherlands. [Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands. [Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands. RP van Duijn, CM (reprint author), Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. EM c.vanduijn@erasmusmc.nl RI Wilson, James F/A-5704-2009; Polasek, Ozren/B-6002-2011; Rivadeneira, Fernando/O-5385-2015; Slagboom, P. Eline/R-4790-2016; Verweij, Niek/A-4499-2017; Feitosa, Mary/K-8044-2012; Suchiman, H. Eka D./F-5024-2017; de Bakker, Paul/B-8730-2009; Ye, Kai/B-3640-2012; OI Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; Rivadeneira, Fernando/0000-0001-9435-9441; Slagboom, P. Eline/0000-0002-2875-4723; Feitosa, Mary/0000-0002-0933-2410; Suchiman, H. Eka D./0000-0002-7168-5516; de Bakker, Paul/0000-0001-7735-7858; van Schaik, Barbera/0000-0002-5568-8127; Joshi, Peter/0000-0002-6361-5059; Sijbrands, Eric/0000-0001-8857-7389; Hocking, Lynne J/0000-0002-2414-2826; Beekman, Marian/0000-0003-0585-6206; Deelen, Joris/0000-0003-4483-3701; Mbarek, Hamdi/0000-0002-1108-0371; Medina-Gomez, Carolina/0000-0001-7999-5538; Verweij, Niek/0000-0002-4303-7685; Wolffenbuttel, Bruce H.R./0000-0001-9262-6921; Karssen, Lennart C./0000-0002-1959-342X; de Geus, Eco/0000-0001-6022-2666 FU Netherlands Organization for Scientific Research [184021007]; NHLBI [HHSN268201200036C, HHSN268200800007C, HHSN268200960009C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, 5R01HL08770003, HL-54776, N01-HC-95159, N01-HC-95169, RR-024156, N02.HL.6.4278]; NHLBI from the National Institute of Neurological Disorders and Stroke (NINDS) [HL080295, HL087652, HL105756, HL103612]; National Institute on Aging (NIA) [AG023629]; European Commission FP-6 STRP [018947 (LSHG-CT-2006-01947)]; European Community's Seventh Framework Programme (FP7) [HEALTH-F4-2007201413]; European Commission under the programme 'Quality of Life and Management of the Living Resources' of 5th Framework Programme [QLG2-CT2002- 01254]; Netherlands Organisation for Scientific Research; Russian Foundation for Basic Research [NWO-RFBR 047.017.043]; BBMRI-NL; Dutch government [NWO 184.021.007]; Netherlands Scientific Organization [NWO 480-05-003]; Dutch Brain Foundation; VU University Amsterdam; NIDDK [5R01DK06833603, 5R01DK07568102]; NHLBI Framingham Heart Study [N01-HC-25195]; Affymetrix Inc for genotyping services [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at the Boston University School of Medicine and Boston Medical Center; National Heart, Lung, and Blood Institute (NHLBI) [R01-HL-087700, R01-HL-088215]; Netherlands Organization for Scientific Research (NWO); MagW/ZonMW [Middelgroot-911-09-032, Spinozapremie 56-464-14192]; Geestkracht programme of the Netherlands Organization for Health Research and Development (Zon-MW) [10-000-1002]; Center for Medical Systems Biology (CSMB, NWO Genomics); NBIC/BioAssist/RK [2008.024]; Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL) [184.021.007]; VU University's Institute for Health and Care Research (EMGO+); Neuroscience Campus Amsterdam (NCA); European Science Foundation (ESF) [EU/QLRT-200101254]; European Community's Seventh Framework Program (FP7); ENGAGE [HEALTH-F4-2007-201413]; European Science Council (ERC) [230374, 284167]; Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health, Rutgers University Cell and DNA Repository [NIMH U24 MH068457-06]; Avera Institute, Sioux Falls, South Dakota (USA); National Institutes of Health (NIH) [R01 HD042157-01A1, MH081802, 1RC2 MH089951, 1RC2 MH089995]; Dtuch Kidney Foundation [E033]; EU [037697]; National Institutes of Health [2R01LM010098]; Netherlands Organisation for Health Research and Development [175.010.2007.006]; NWO VENI [916.761.70]; ZonMw [90.700.441]; Dutch Inter University Cardiology Institute Netherlands (ICIN); investigator-initiated grant obtained from Bristol-Myers Squibb; Established Clinical Investigator of the Netherlands Heart Foundation [2001 D 032]; seventh framework programme of the European commission [223004]; Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging) [050-060-810]; Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; Netherlands Organisation of Scientific Research NWO Investments [175.010.2005.011, 911-03-012]; Research Institute for Diseases in the Elderly [014-93-015]; Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) [050-060-810] FX We especially thank all volunteers who participated in our study. This study made use of data generated by the 'Genome of the Netherlands' project, which is funded by the Netherlands Organization for Scientific Research (grant no. 184021007). The data were made available as a Rainbow Project of BBMRI-NL. Samples were contributed by LifeLines (http://lifelines. nl/lifelines-research/general), the Leiden Longevity Study (http://www. healthy-ageing. nl; http://www. langleven. net), the Netherlands Twin Registry (NTR: http://www. tweelingenregister. org), the Rotterdam studies (http://www. erasmus-epidemiology. nl/rotterdamstudy) and the Genetic Research in Isolated Populations programme (http://www. epib. nl/research/geneticepi/research. html# gip). The sequencing was carried out in collaboration with the Beijing Institute for Genomics (BGI).; We would like to thank all the members of the CHARGE Lipids Working Group for their contribution in this project (a full list of consortium members is provided in Supplementary Note 1).; Cardiovascular Health Study: This CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, HHSN268200960009C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI grants HL080295, HL087652, HL105756 and HL103612 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through AG023629 from the National Institute on Aging (NIA). A full list of CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm.; The ERF study as a part of EuroSPAN (European Special Populations Research Network) was supported by European Commission FP-6 STRP grant number 018947 (LSHG-CT-2006-01947) and also received funding from the European Community's Seventh Framework Programme (FP7/2007-2013)/grant agreement HEALTH-F4-2007201413 by the European Commission under the programme 'Quality of Life and Management of the Living Resources' of 5th Framework Programme (no. QLG2-CT2002- 01254). High-throughput analysis of the ERF data was supported by joint grant from the Netherlands Organisation for Scientific Research and the Russian Foundation for Basic Research (NWO-RFBR 047.017.043). This research was financially supported by BBMRI-NL, a Research Infrastructure financed by the Dutch government (NWO 184.021.007). Statistical analyses for the ERF study were carried out on the Genetic Cluster Computer (http://www. geneticcluster. org), which is financially supported by the Netherlands Scientific Organization (NWO 480-05-003 PI: Posthuma) along with a supplement from the Dutch Brain Foundation and the VU University Amsterdam. We are grateful to all study participants and their relatives, general practitioners and neurologists for their contributions and to P. Veraart for her help in genealogy, J. Vergeer for the supervision of the laboratory work and P. Snijders for his help in data collection.; The FamHS is funded by a NHLBI grant 5R01HL08770003, and NIDDK grants 5R01DK06833603 and 5R01DK07568102.; The Framingham Heart Study SHARe Project for GWAS scan was supported by the NHLBI Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix Inc for genotyping services (Contract No. N02-HL-6-4278). DNA isolation and biochemistry were partly supported by NHLBI HL-54776. A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at the Boston University School of Medicine and Boston Medical Center. We are grateful to Han Chen for conducting the 1000G imputation.; The Family Heart Study was supported by the by grants R01-HL-087700 and R01-HL-088215 from the National Heart, Lung, and Blood Institute (NHLBI).; MESA Whites and the MESA SHARe project are conducted and supported by contracts N01-HC-95159 through N01-HC-95169 and RR-024156 from the NHLBI. Funding for MESA SHARe genotyping was provided by NHLBI Contract N02.HL.6.4278. MESA Family is conducted and supported in collaboration with MESA investigators; support is provided by grants and contracts R01HL071051, R01HL071205, R01HL071250, R01HL071251, R01HL071252, R01HL071258 and R01HL071259. We thank the participants of the MESA study, the Coordinating Center, MESA investigators and study staff for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org.; Netherland Twin Register (NTR) and Netherlands Study of Depression and Anxiety (NESDA): Funding was obtained from the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants Middelgroot-911-09-032, Spinozapremie 56-464-14192, Geestkracht programme of the Netherlands Organization for Health Research and Development (Zon-MW, grant number 10-000-1002), Center for Medical Systems Biology (CSMB, NWO Genomics), NBIC/BioAssist/RK(2008.024), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL, 184.021.007), VU University's Institute for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam (NCA); the European Science Foundation (ESF, EU/QLRT-200101254), the European Community's Seventh Framework Program (FP7/2007-2013), ENGAGE (HEALTH-F4-2007-201413); the European Science Council (ERC Advanced, 230374); and the European Research Council (ERC-284167). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health, Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the Avera Institute, Sioux Falls, South Dakota (USA) and the National Institutes of Health (NIH R01 HD042157-01A1, MH081802, Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995).; PREVEND genetics is supported by the Dtuch Kidney Foundation (Grant E033), the EU project grant GENECURE (FP-6 LSHM CT 2006 037697), the National Institutes of Health (grant 2R01LM010098), The Netherlands Organisation for Health Research and Development (NWO-Groot grant 175.010.2007.006, NWO VENI grant 916.761.70, ZonMw grant 90.700.441) and the Dutch Inter University Cardiology Institute Netherlands (ICIN).; The PROSPER study was supported by an investigator-initiated grant obtained from Bristol-Myers Squibb. J. W. J is an Established Clinical Investigator of the Netherlands Heart Foundation (grant 2001 D 032). Genotyping was supported by the seventh framework programme of the European commission (grant 223004) and by the Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging grant 050-060-810).; The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII) and the Municipality of Rotterdam. We are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists.; The generation and management of GWAS genotype data for the Rotterdam Study is supported by the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012). This study is funded by the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) project no. 050-060-810. We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth Herrera and Marjolein Peters for their help in creating the GWAS database. NR 22 TC 7 Z9 7 U1 0 U2 7 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 MAR PY 2015 VL 6 AR UNSP 6065 DI 10.1038/ncomms7065 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CF5ZF UT WOS:000352635400001 PM 25751400 ER PT J AU Collaco, JM Aherrera, AD Breysse, PN Winickoff, JP Klein, JD McGrath-Morrow, SA AF Collaco, Joseph M. Aherrera, Angela D. Breysse, Patrick N. Winickoff, Jonathan P. Klein, Jonathan D. McGrath-Morrow, Sharon A. TI Hair Nicotine Levels in Children With Bronchopulmonary Dysplasia SO PEDIATRICS LA English DT Article ID SECONDHAND SMOKE EXPOSURE; BIRTH-WEIGHT INFANTS; TOBACCO-SMOKE; CIGARETTE-SMOKE; PRETERM INFANTS; DISEASE; REHOSPITALIZATION; MORBIDITY; GROWTH; WOMEN AB BACKGROUND: Tobacco smoke exposure (TSE) may increase respiratory morbidities in young children with bronchopulmonary dysplasia (BPD). Rapid respiratory rates, close proximity to a smoking caregiver, and increased dermal absorption of tobacco smoke components can contribute to systemic exposure. In this study, hair nicotine levels were used as a biomarker of chronic TSE in young children with BPD to determine if hair nicotine levels correlate with caregiver self-report of TSE and respiratory morbidities. METHODS: From 2012 to 2014, hair nicotine levels were measured from consecutive children seen in a BPD outpatient clinic and compared with caregiver questionnaires on household smoking. The relationship between respiratory morbidities and self-reported TSE or hair nicotine level was assessed. RESULTS: The mean hair nicotine level from 117 children was 3.1 +/- 13.2 ng/mg. Hair nicotine levels were significantly higher in children from smoking households by caregiver self-report compared with caregivers who reported no smoking (8.2 +/- 19.7 ng/mg vs 1.8 +/- 10.7; P < .001). In households that reported smoking, hair nicotine levels were higher in children with a primary caregiver who smoked compared with a primary caregiver who did not smoke. Among children with BPD who required respiratory support (n = 50), a significant association was found between higher log hair nicotine levels and increased hospitalizations and limitation of activity. CONCLUSIONS: Chronic TSE is common in children with BPD, with hair nicotine levels being more likely to detect TSE than caregiver self-report. Hair nicotine levels were also a better predictor of hospitalization and activity limitation in children with BPD who required respiratory support at outpatient presentation. C1 [Collaco, Joseph M.; Aherrera, Angela D.; McGrath-Morrow, Sharon A.] Johns Hopkins Sch Med, Eudowood Div Pediat Resp Sci, Baltimore, MD USA. [Breysse, Patrick N.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Collaco, Joseph M.; Breysse, Patrick N.; Winickoff, Jonathan P.; Klein, Jonathan D.; McGrath-Morrow, Sharon A.] Amer Acad Pediat, Julius B Richmond FAMRI Ctr Excellence, Elk Grove Village, IL USA. [Winickoff, Jonathan P.] Massachusetts Gen Hosp, Div Gen Pediat, Boston, MA 02114 USA. [Winickoff, Jonathan P.] Harvard Univ, Sch Med, Boston, MA USA. RP Collaco, JM (reprint author), Eudowood Div Pediat Resp Sci, David M Rubenstein Bldg,200 North Wolfe St, Baltimore, MD 21287 USA. EM mcollac1@jhmi.edu FU Center of Excellence grant from the Flight Attendant Medical Research Institute; Johns Hopkins Center of Excellence grant from the Flight Attendant Medical Research Institute FX Funded by a Center of Excellence grant to the American Academy of Pediatrics from the Flight Attendant Medical Research Institute and a Johns Hopkins Center of Excellence grant from the Flight Attendant Medical Research Institute. NR 27 TC 5 Z9 5 U1 0 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD MAR PY 2015 VL 135 IS 3 BP E678 EP E686 DI 10.1542/peds.2014-2501 PG 9 WC Pediatrics SC Pediatrics GA CF0BD UT WOS:000352206600016 PM 25647675 ER PT J AU Speltz, ML Collett, BR Wallace, ER Starr, JR Cradock, MM Buono, L Cunningham, M Kapp-Simon, K AF Speltz, Matthew L. Collett, Brent R. Wallace, Erin R. Starr, Jacqueline R. Cradock, Mary Michaeleen Buono, Lauren Cunningham, Michael Kapp-Simon, Kathleen TI Intellectual and Academic Functioning of School-Age Children With Single-Suture Craniosynostosis SO PEDIATRICS LA English DT Article ID NONSYNDROMIC CRANIOSYNOSTOSIS; INFANTS; NEURODEVELOPMENT; PRESSURE; OUTCOMES; BRAIN AB OBJECTIVE: We compared the developmental status of school-age children with single-suture craniosynostosis (case group) and unaffected children (control group). Within the case group we compared the performance of children distinguished by location of suture fusion (sagittal, metopic, unicoronal, lambdoid). METHODS: We administered standardized tests of intelligence, reading, spelling, and math to 182 case participants and 183 control participants. This sample represented 70% of those tested during infancy before case participants had corrective surgery. RESULTS: After adjustment for demographics, case participants' average scores were lower than those of control participants on all measures. The largest observed differences were in Full-Scale IQ and math computation, where case participants' adjusted mean scores were 2.5 to 4 points lower than those of control participants (Ps ranged from.002 to .09). Adjusted mean case-control differences on other measures of achievement were modest, although case deficits became more pronounced after adjustment for participation in developmental interventions. Among case participants, 58% had no discernible learning problem (score <25th percentile on a standardized achievement test). Children with metopic, unicoronal, and lambdoid synostosis tended to score lower on most measures than did children with sagittal fusions (Ps ranged from, <.001 to .82). CONCLUSIONS: The developmental delays observed among infants with single-suture craniosynostosis are partially evident at school age, as manifested by lower average scores than those of control participants on measures of IQ and math. However, case participants' average scores were only slightly lower than those of control participants on reading and spelling measures, and the frequency of specific learning problems was comparable. Among case participants, those with unicoronal and lambdoid fusions appear to be the most neurodevelopmentally vulnerable. C1 [Speltz, Matthew L.; Collett, Brent R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Cunningham, Michael] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Speltz, Matthew L.; Collett, Brent R.; Wallace, Erin R.] Seattle Childrens Res Inst, Ctr Child Hlth Behav & Dev, Seattle, WA 98121 USA. [Starr, Jacqueline R.] Forsyth Inst, Dept Clin & Translat Res, Cambridge, MA USA. [Starr, Jacqueline R.] Harvard Univ, Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA 02115 USA. [Cradock, Mary Michaeleen] St Louis Childrens Hosp, Dept Psychol, St Louis, MO 63178 USA. [Cradock, Mary Michaeleen] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Buono, Lauren] Childrens Healthcare Atlanta, Ctr Craniofacial Disorders, Atlanta, GA USA. [Cunningham, Michael] Seattle Childrens Hosp, Craniofacial Ctr, Seattle, WA USA. [Kapp-Simon, Kathleen] Northwestern Univ, Dept Surg, Chicago, IL USA. [Kapp-Simon, Kathleen] Shriners Hosp Children, Chicago, IL USA. RP Speltz, ML (reprint author), Seattle Childrens Res Inst, 2001 8th Ave,Suite 600,Mailstop CW8-6, Seattle, WA 98121 USA. EM matt.speltz@seattlechildrens.org FU National Institutes of Health (NIH) from the National Institute of Dental and Craniofacial Research [R01 DE 13813, R01 DE 018227]; Jean Renny Endowment for Craniofacial Medicine; National Institutes of Health (NIH) FX All phases of this study were supported by National Institutes of Health (NIH) grant R01 DE 13813 (Dr Speltz) and R01 DE 018227 (Dr Cunningham) from the National Institute of Dental and Craniofacial Research. Dr Cunningham was also supported by the Jean Renny Endowment for Craniofacial Medicine. Funded by the National Institutes of Health (NIH). NR 44 TC 14 Z9 14 U1 0 U2 8 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD MAR PY 2015 VL 135 IS 3 BP E615 EP E623 DI 10.1542/peds.2014-1634 PG 9 WC Pediatrics SC Pediatrics GA CF0BD UT WOS:000352206600009 PM 25713274 ER PT J AU Yang, F Petsalaki, E Rolland, T Hill, DE Vidal, M Roth, FP AF Yang, Fan Petsalaki, Evangelia Rolland, Thomas Hill, David E. Vidal, Marc Roth, Frederick P. TI Protein Domain-Level Landscape of Cancer-Type-Specific Somatic Mutations SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; EPIDERMAL GROWTH-FACTOR; P53 TUMOR-SUPPRESSOR; HEPATOCELLULAR-CARCINOMA; PROSTATE-CANCER; GENOMIC ANALYSIS; HUMAN BREAST; LUNG-CANCER; ESOPHAGEAL ADENOCARCINOMA; INACTIVATING MUTATIONS AB Identifying driver mutations and their functional consequences is critical to our understanding of cancer. Towards this goal, and because domains are the functional units of a protein, we explored the protein domain-level landscape of cancer-type-specific somatic mutations. Specifically, we systematically examined tumor genomes from 21 cancer types to identify domains with high mutational density in specific tissues, the positions of mutational hotspots within these domains, and the functional and structural context where possible. While hotspots corresponding to specific gain-of-function mutations are expected for oncoproteins, we found that tumor suppressor proteins also exhibit strong biases toward being mutated in particular domains. Within domains, however, we observed the expected patterns of mutation, with recurrently mutated positions for oncogenes and evenly distributed mutations for tumor suppressors. For example, we identified both known and new endometrial cancer hotspots in the tyrosine kinase domain of the FGFR2 protein, one of which is also a hotspot in breast cancer, and found new two hotspots in the Immunoglobulin I-set domain in colon cancer. Thus, to prioritize cancer mutations for further functional studies aimed at more precise cancer treatments, we have systematically correlated mutations and cancer types at the protein domain level. C1 [Yang, Fan; Roth, Frederick P.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Yang, Fan; Petsalaki, Evangelia; Roth, Frederick P.] Univ Toronto, Donnelly Ctr, Toronto, ON, Canada. [Yang, Fan; Petsalaki, Evangelia; Roth, Frederick P.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Rolland, Thomas; Hill, David E.; Vidal, Marc; Roth, Frederick P.] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. [Rolland, Thomas] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Roth, Frederick P.] Canadian Inst Adv Res, Toronto, ON, Canada. [Roth, Frederick P.] Univ Toronto, Dept Comp Sci, Toronto, ON, Canada. RP Yang, F (reprint author), Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. EM fritz.roth@utoronto.ca RI Roth, Frederick/H-6308-2011; OI Petsalaki, Evangelia/0000-0002-8294-2995; Roth, Frederick/0000-0002-6628-649X FU NIH/NHGRI Center of Excellence in Genome Science award [HG004233]; NIH/NHGRI [HG001715]; Canada Excellence Research Chairs Program; Avon Foundation; Ontario Research Fund - Research Excellence Award; Canadian Institute for Advanced Research Fellowship FX This project was supported by an NIH/NHGRI Center of Excellence in Genome Science award (HG004233) and benefitted from NIH/NHGRI award HG001715 (both to MV, DEH, and FPR). FPR was also supported by the Canada Excellence Research Chairs Program, by the Avon Foundation, by an Ontario Research Fund - Research Excellence Award, and by a Canadian Institute for Advanced Research Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 143 TC 15 Z9 15 U1 2 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD MAR PY 2015 VL 11 IS 3 AR UNSP e1004147 DI 10.1371/journal.pcbi.1004147 PG 30 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA CE9XB UT WOS:000352195700038 PM 25794154 ER PT J AU Siedner, MJ Gostin, LO Cranmer, HH Kraemer, JD AF Siedner, Mark J. Gostin, Lawrence O. Cranmer, Hilarie H. Kraemer, John D. TI Strengthening the Detection of and Early Response to Public Health Emergencies: Lessons from the West African Ebola Epidemic SO PLOS MEDICINE LA English DT Article ID COMMUNITY ADVISORY BOARDS; GLOBAL HEALTH; VIRUS DISEASE C1 [Siedner, Mark J.; Cranmer, Hilarie H.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Siedner, Mark J.; Cranmer, Hilarie H.] Harvard Univ, Sch Med, Boston, MA USA. [Gostin, Lawrence O.; Kraemer, John D.] Georgetown Univ, ONeill Inst Natl & Global Hlth Law, Washington, DC USA. [Kraemer, John D.] Georgetown Univ, Dept Hlth Syst Adm, Washington, DC USA. RP Siedner, MJ (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. EM msiedner@mgh.harvard.edu FU NIMH NIH HHS [K23 MH099916] NR 33 TC 12 Z9 12 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD MAR PY 2015 VL 12 IS 3 AR e1001804 DI 10.1371/journal.pmed.1001804 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CE8MI UT WOS:000352096300012 PM 25803303 ER PT J AU Dinter, J Duong, E Lai, NY Berberich, MJ Kourjian, G Bracho-Sanchez, E Chu, D Su, H Zhang, SC Le Gall, S AF Dinter, Jens Duong, Ellen Lai, Nicole Y. Berberich, Matthew J. Kourjian, Georgio Bracho-Sanchez, Edith Chu, Duong Su, Hang Zhang, Shao Chong Le Gall, Sylvie TI Variable Processing and Cross-presentation of HIV by Dendritic Cells and Macrophages Shapes CTL Immunodominance and Immune Escape SO PLOS PATHOGENS LA English DT Article ID MHC CLASS-I; T-LYMPHOCYTE EPITOPES; VIRUS TYPE-1 INFECTION; CONTROLS PHAGOSOMAL PH; ANTIGEN PRESENTATION; PEPTIDE STABILITY; VIRAL REPLICATION; VACCINE DESIGN; CUTTING EDGE; RESPONSES AB Dendritic cells (DCs) and macrophages (Mos) internalize and process exogenous HIV-derived antigens for cross-presentation by MHC-I to cytotoxic CD8(+) T cells (CTL). However, how degradation patterns of HIV antigens in the cross-presentation pathways affect immunodominance and immune escape is poorly defined. Here, we studied the processing and cross-presentation of dominant and subdominant HIV-1 Gag-derived epitopes and HLA-restricted mutants by monocyte-derived DCs and Mos. The cross-presentation of HIV proteins by both DCs and Mos led to higher CTL responses specific for immunodominant epitopes. The low CTL responses to subdominant epitopes were increased by pretreatment of target cells with peptidase inhibitors, suggestive of higher intracellular degradation of the corresponding peptides. Using DC and Mo cell extracts as a source of cytosolic, endosomal or lysosomal proteases to degrade long HIV peptides, we identified by mass spectrometry cell-specific and compartment-specific degradation patterns, which favored the production of peptides containing immunodominant epitopes in all compartments. The intracellular stability of optimal HIV-1 epitopes prior to loading onto MHC was highly variable and sequence-dependent in all compartments, and followed CTL hierarchy with immunodominant epitopes presenting higher stability rates. Common HLA-associated mutations in a dominant epitope appearing during acute HIV infection modified the degradation patterns of long HIV peptides, reduced intracellular stability and epitope production in cross-presentation-competent cell compartments, showing that impaired epitope production in the cross-presentation pathway contributes to immune escape. These findings highlight the contribution of degradation patterns in the cross-presentation pathway to HIV immunodominance and provide the first demonstration of immune escape affecting epitope cross-presentation. C1 [Dinter, Jens; Duong, Ellen; Lai, Nicole Y.; Berberich, Matthew J.; Kourjian, Georgio; Bracho-Sanchez, Edith; Chu, Duong; Su, Hang; Zhang, Shao Chong; Le Gall, Sylvie] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Cambridge, MA 02138 USA. RP Dinter, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Cambridge, MA 02138 USA. EM sylvie_legall@hms.harvard.edu FU NIAID [R01 AI084753, R01 AI084106]; Ernst Schering Foundation FX The project was funded by grants R01 AI084753 and R01 AI084106 from NIAID to SLG. JD is funded in part by a Ph.D. training fellowship from the Ernst Schering Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 76 TC 9 Z9 9 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD MAR PY 2015 VL 11 IS 3 AR UNSP e1004725 DI 10.1371/journal.ppat.1004725 PG 22 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA CE9ZI UT WOS:000352201900045 PM 25781895 ER PT J AU Moutsopoulos, NM Chalmers, NI Barb, JJ Abusleme, L Greenwell-Wild, T Dutzan, N Paster, BJ Munson, PJ Fine, DH Uzel, G Holland, SM AF Moutsopoulos, Niki M. Chalmers, Natalia I. Barb, Jennifer J. Abusleme, Loreto Greenwell-Wild, Teresa Dutzan, Nicolas Paster, Bruce J. Munson, Peter J. Fine, Daniel H. Uzel, Gulbu Holland, Steven M. TI Subgingival Microbial Communities in Leukocyte Adhesion Deficiency and Their Relationship with Local Immunopathology SO PLOS PATHOGENS LA English DT Article ID AGGRESSIVE PERIODONTITIS; AGGREGATIBACTER-ACTINOMYCETEMCOMITANS; IDENTIFICATION MICROARRAY; PORPHYROMONAS-GINGIVALIS; REFRACTORY PERIODONTITIS; INFECTION; INFLAMMATION; RESPONSES; CHILDREN; HEALTH AB Leukocyte Adhesion Deficiency I (LAD-I) is a primary immunodeficiency caused by single gene mutations in the CD18 subunit of beta 2 integrins which result in defective transmigration of neutrophils into the tissues. Affected patients suffer from recurrent life threatening infections and severe oral disease (periodontitis). Microbial communities in the local environment (subgingival plaque) are thought to be the triggers for inflammatory periodontitis, yet little is known regarding the microbial communities associated with LAD-I periodontitis. Here we present the first comprehensive characterization of the subgingival communities in LAD-I, using a 16S rRNA gene-based microarray, and investigate the relationship of this tooth adherent microbiome to the local immunopathology of periodontitis. We show that the LAD subgingival microbiome is distinct from that of health and Localized Aggressive Periodontitits. Select periodontitis-associated species in the LAD microbiome included Parvimonas micra, Porphyromonas endodontalis, Eubacterium brachy and Treponema species. Pseudomonas aeruginosa, a bacterium not typically found in subgingival plaque is detected in LAD-I. We suggest that microbial products from LAD-associated communities may have a role in stimulating the local inflammatory response. We demonstrate that bacterial LPS translocates into the lesions of LAD-periodontitis potentially triggering immunopathology. We also show in in vitro assays with human macrophages and in vivo in animal models that microbial products from LAD-associated subgingival plaque trigger IL-23-related immune responses, which have been shown to dominate in patient lesions. In conclusion, our current study characterizes the subgingival microbial communities in LAD-periodontitis and supports their role as triggers of disease pathogenesis. C1 [Moutsopoulos, Niki M.; Abusleme, Loreto; Greenwell-Wild, Teresa; Dutzan, Nicolas] Natl Inst Dent & Craniofacial Res, Oral Immun & Inflammat Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. [Chalmers, Natalia I.] Natl Inst Dent & Craniofacial Res, Clin Res Core, NIH, Bethesda, MD USA. [Barb, Jennifer J.; Munson, Peter J.] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. [Paster, Bruce J.] Forsyth Inst, Cambridge, MA USA. [Paster, Bruce J.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Fine, Daniel H.] Rutgers State Univ, Rutgers Sch Dent Med, Newark, NJ 07102 USA. [Uzel, Gulbu; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Moutsopoulos, NM (reprint author), Natl Inst Dent & Craniofacial Res, Oral Immun & Inflammat Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. EM nmoutsop@mail.nih.gov FU Intramural Research Program of the NIH; National Institute of Dental and Craniofacial Research (NIDCR); National Institute of Allergy and Infectious Diseases (NIAID) FX This research was supported in part by the Intramural Research Program of the NIH, National Institute of Dental and Craniofacial Research (NIDCR) and National Institute of Allergy and Infectious Diseases (NIAID). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 10 Z9 10 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD MAR PY 2015 VL 11 IS 3 AR e1004698 DI 10.1371/journal.ppat.1004698 PG 19 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA CE9ZI UT WOS:000352201900027 PM 25741691 ER PT J AU Freer, PE AF Freer, Phoebe E. TI Mammographic Breast Density: Impact on Breast Cancer Risk and Implications for Screening SO RADIOGRAPHICS LA English DT Article ID DIGITAL MAMMOGRAPHY; DIAGNOSTIC-ACCURACY; ASYMPTOMATIC WOMEN; 1ST EVALUATION; ELEVATED RISK; FAMILIAL RISK; ULTRASOUND; TOMOSYNTHESIS; MRI; US AB Mammographic breast density is rapidly becoming a hot topic in both the medical literature and the lay press. In the United States, recent legislative changes in 19 states now require radiologists to notify patients regarding breast density as well as the possible need for supplemental screening. Federal legislation regarding breast density notification has been introduced, and its passage is likely on the horizon. An understanding of the context, scientific evidence, and controversies surrounding the topic of breast density as a risk factor for breast cancer is critical for radiologists. The current state of evidence is presented regarding supplemental screening for women with dense breasts, including the use of digital breast tomo-synthesis, whole-breast ultrasonography, and gadolinium-enhanced magnetic resonance imaging. A review of current practice guidelines and additional sources of information will improve radiologists' understanding of the relevant subject of breast density and enable them to respond appropriately to questions from patients, clinicians, and the media. (C) RSNA, 2015. C1 Massachusetts Gen Hosp, MGH Imaging, Dept Radiol, Boston, MA 02114 USA. RP Freer, PE (reprint author), Massachusetts Gen Hosp, MGH Imaging, Dept Radiol, 15 Pk Man St,Wang Bldg,ACC 240, Boston, MA 02114 USA. EM pfreer@partners.org OI Freer, Phoebe/0000-0001-6886-7100 NR 84 TC 18 Z9 18 U1 0 U2 13 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAR-APR PY 2015 VL 35 IS 2 BP 302 EP 315 DI 10.1148/rg.352140106 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CF4YR UT WOS:000352561000001 PM 25763718 ER PT J AU Gunn, AJ Mangano, MD Choy, G Sahani, DV AF Gunn, Andrew J. Mangano, Mark D. Choy, Garry Sahani, Dushyant V. TI Rethinking the Role of the Radiologist: Enhancing Visibility through Both Traditional and Nontraditional Reporting Practices SO RADIOGRAPHICS LA English DT Article ID REFERRING PHYSICIANS; PREFERENCES; COMMUNICATION; STYLE AB The written radiology report is the primary method by which the radiologist communicates examination findings to the referring physician and the patient. Unfortunately, despite recent efforts to improve radiology reporting practices, dissatisfaction with regard to traditional reporting practices continues among referring physicians and patients. Moreover, the current reporting paradigm limits the amount of interaction that radiologists can have with patients and referring physicians. To address these issues, organizational efforts have been made by the Radiological Society of North America and the American College of Radiology to educate the public about the role of the radiologist in patient care, provide resources for individuals to learn more about the practice of radiology, and assist radiologists in creating a more "patient-centered" practice. In addition, individual radiologists may want to consider making adjustments to their reporting practices to improve communication of examination findings and increase patient awareness of the radiologist's role in clinical care. Many opportunities exist for radiologists to make such changes, both within the traditional reporting model (decreasing barriers to communication, educating patients) and with implementation of various nontraditional reporting practices (eg, delivering examination results directly to patients, receiving structured feedback on reports, establishing a diagnostic radiology consultation clinic). The authors provide guidance for radiologists who wish to enhance their visibility in clinical care with use of both traditional and nontraditional reporting practices. (C) RSNA, 2015 C1 [Gunn, Andrew J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gunn, AJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM ajgunnmd@gmail.com NR 38 TC 11 Z9 11 U1 1 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAR-APR PY 2015 VL 35 IS 2 BP 416 EP 423 DI 10.1148/rg.352140042 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CF4YR UT WOS:000352561000009 PM 25763726 ER PT J AU Kwak, JJ Tirumani, SH Van den Abbeele, AD Koo, PJ Jacene, HA AF Kwak, Jennifer J. Tirumani, Sree Harsha Van den Abbeele, Annick D. Koo, Phillip J. Jacene, Heather A. TI Cancer Immunotherapy: Imaging Assessment of Novel Treatment Response Patterns and Immunerelated Adverse Events SO RADIOGRAPHICS LA English DT Article ID METASTATIC MELANOMA; IN-VIVO; IPILIMUMAB; THERAPY; BLOCKADE; ANTIBODY; CRITERIA; SAFETY; CTLA-4 AB Cancer immunotherapy is changing the imaging evaluation of cancer treatment response and treatment-related toxic effects. New emerging patterns of treatment response and treatment-related toxic effects after treatment with immunomodulating agents have been observed. Treatment response after immunomodulatory therapy can be associated with significantly delayed decrease in tumor size, and new or enlarging tumors observed soon after completion of treatment may not reflect disease progression. In addition, activation of the immune system to fight cancer may lead to unwanted autoimmune-mediated toxic effects that could be mistaken for metastatic disease or misdiagnosed as a non-treatment-related process and delay appropriate clinical management. Radiologists must recognize the novel treatment response patterns and the wide range of autoimmune toxic effects, which should not be mistaken for treatment failure or metastatic disease progression. (C) RSNA, 2015 C1 [Kwak, Jennifer J.; Koo, Phillip J.] Univ Colorado, Sch Med, Dept Radiol, Aurora, CO 80045 USA. [Tirumani, Sree Harsha; Van den Abbeele, Annick D.; Jacene, Heather A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Tirumani, Sree Harsha; Van den Abbeele, Annick D.; Jacene, Heather A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Kwak, JJ (reprint author), Univ Colorado, Sch Med, Dept Radiol, Anschutz Med Campus,12700 E 19th Ave,Room C278, Aurora, CO 80045 USA. EM jen.j.kwak@gmail.com NR 22 TC 8 Z9 8 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAR-APR PY 2015 VL 35 IS 2 BP 424 EP 437 DI 10.1148/rg.352140121 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CF4YR UT WOS:000352561000010 PM 25763727 ER PT J AU Tirumani, SH Fairchild, A Krajewski, KM Nishino, M Howard, SA Baheti, AD Rosenthal, MH Jagannathan, JP Shinagare, AB Ramaiya, NH AF Tirumani, Sree Harsha Fairchild, Alexandra Krajewski, Katherine M. Nishino, Mizuki Howard, Stephanie A. Baheti, Akshay D. Rosenthal, Michael H. Jagannathan, Jyothi P. Shinagare, Atul B. Ramaiya, Nikhil H. TI Anti-VEGF Molecular Targeted Therapies in Common Solid Malignancies: Comprehensive Update for Radiologists SO RADIOGRAPHICS LA English DT Article ID RENAL-CELL CARCINOMA; GASTROINTESTINAL STROMAL TUMORS; ADVANCED HEPATOCELLULAR-CARCINOMA; VENOUS THROMBOEMBOLIC EVENTS; RESPONSE EVALUATION CRITERIA; COLORECTAL LIVER METASTASES; CONTRAST-ENHANCED CT; SOFT-TISSUE SARCOMAS; LUNG-CANCER; ANTIANGIOGENIC THERAPY AB Angiogenesis is an essential component of the growth and dissemination of solid malignancies and is mediated by several proangiogenic factors. The most widely studied proangiogenic factor is vascular endothelial growth factor (VEGF). A major class of molecular targeted therapies (MTTs) inhibit the VEGF axis and are referred to as antiangiogenic MTTs. There are two main types of anti-VEGF MTTs: drugs targeting circulating VEGF and drugs interfering with the activity of the VEGF receptors. The cancers against which antiangiogenic MTTs have had the greatest effect are gliomas, non-small cell lung cancer, colorectal cancer, hepatocellular carcinoma, renal cell carcinoma, and gastrointestinal stromal tumor. These cancers respond to antiangiogenic MTTs in a different way than they respond to conventional chemotherapy. Instead of the traditional Response Evaluation Criteria in Solid Tumors (RECIST), each of these cancers therefore requires its own individualized treatment response criteria (TRC). Examples of individualized TRC include the Response Assessment in Neurooncology (RANO) criteria for gliomas, modified RECIST for hepatocellular carcinoma, and Morphology, Attenuation, Size, and Structure (MASS) criteria for renal cell carcinoma. Furthermore, antiangiogenic MTTs have a unique spectrum of class-specific and drug-specific toxic effects, some of which can be detected at imaging. Increasing use of antiangiogenic MTTs in clinical practice necessitates that radiologists be aware of these drugs, their response patterns, and TRC as well as their toxic effect profiles. (C) RSNA, 2015 C1 [Tirumani, Sree Harsha; Krajewski, Katherine M.; Nishino, Mizuki; Howard, Stephanie A.; Baheti, Akshay D.; Rosenthal, Michael H.; Jagannathan, Jyothi P.; Shinagare, Atul B.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Tirumani, Sree Harsha; Fairchild, Alexandra; Krajewski, Katherine M.; Nishino, Mizuki; Howard, Stephanie A.; Baheti, Akshay D.; Rosenthal, Michael H.; Jagannathan, Jyothi P.; Shinagare, Atul B.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA. RP Tirumani, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM Sreeharsha_Tiru-mani@DFCI.HARVARD.EDU FU RSNA; General Electric; National Cancer Institute; Harvard Medical School FX A.B.S. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: research grant from RSNA. Other activities: disclosed no relevant relationships. K.M.K. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: grants from General Electric. Other activities: disclosed no relevant relationships. M.N. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: grants from the National Cancer Institute and Harvard Medical School. Other activities: disclosed no relevant relationships. NR 88 TC 7 Z9 8 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAR-APR PY 2015 VL 35 IS 2 BP 455 EP 474 DI 10.1148/rg.352140119 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CF4YR UT WOS:000352561000012 PM 25763729 ER PT J AU Scheinfeld, MH Dym, AA Spektor, M Avery, LL Dym, RJ Amanatullah, DF AF Scheinfeld, Meir H. Dym, Akiva A. Spektor, Michael Avery, Laura L. Dym, R. Joshua Amanatullah, Derek F. TI Acetabular Fractures: What Radiologists Should Know and How 3D CT Can Aid Classification SO RADIOGRAPHICS LA English DT Article ID PERCUTANEOUS SCREW FIXATION; COMPUTED-TOMOGRAPHY; HETEROTOPIC OSSIFICATION; POSTERIOR WALL; CONVENTIONAL RADIOGRAPHY; OPERATIVE TREATMENT; MANAGEMENT; INJURY; INDOMETHACIN; STABILITY AB Correct recognition, description, and classification of acetabular fractures is essential for efficient patient triage and treatment. Acetabular fractures may result from high-energy trauma or low-energy trauma in the elderly. The most widely used acetabular fracture classification system among radiologists and orthopedic surgeons is the system of Judet and Letournel, which includes five elementary (or elemental) and five associated fractures. The elementary fractures are anterior wall, posterior wall, anterior column, posterior column, and transverse. The associated fractures are all combinations or partial combinations of the elementary fractures and include transverse with posterior wall, T-shaped, associated both column, anterior column or wall with posterior hemitransverse, and posterior column with posterior wall. The most unique fracture is the associated both column fracture, which completely dissociates the acetabular articular surface from the sciatic buttress. Accurate categorization of acetabular fractures is challenging because of the complex three-dimensional (3D) anatomy of the pelvis, the rarity of certain acetabular fracture variants, and confusing nomenclature. Comparing a 3D image of the fractured acetabulum with a standard diagram containing the 10 Judet and Letournel categories of acetabular fracture and using a flowchart algorithm are effective ways of arriving at the correct fracture classification. Online supplemental material is available for this article. (C) RSNA, 2015.radiographics.rsna.org C1 [Scheinfeld, Meir H.; Dym, R. Joshua] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Radiol, Div Emergency Radiol, Bronx, NY 10467 USA. [Dym, Akiva A.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Spektor, Michael] Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06510 USA. [Avery, Laura L.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Div Emergency Radiol, Boston, MA 02115 USA. [Amanatullah, Derek F.] Stanford Univ, Dept Orthoped Surg, Palo Alto, CA 94304 USA. RP Scheinfeld, MH (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Dept Radiol, Div Emergency Radiol, 111 E 210 St, Bronx, NY 10467 USA. EM mscheinf@montefiore.org FU AONA; Trimed; Acumed; DePuy-Synthes; Medscape; Sanofi FX D.F.A. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: grants from AONA, Trimed, Acumed, and DePuy-Synthes and personal fees from Medscape and Sanofi. Other activities: disclosed no relevant relationships. NR 86 TC 3 Z9 5 U1 3 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAR-APR PY 2015 VL 35 IS 2 BP 555 EP 577 DI 10.1148/rg.352140098 PG 23 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CF4YR UT WOS:000352561000021 PM 25763739 ER PT J AU Yi, JS Federation, AJ Qi, J Dhe-Paganon, S Hadler, M Xu, X St Pierre, R Varca, AC Wu, L Marineau, JJ Smith, WB Souza, A Chory, EJ Armstrong, SA Bradner, JE AF Yi, Joanna S. Federation, Alexander J. Qi, Jun Dhe-Paganon, Sirano Hadler, Michael Xu, Xiang St Pierre, Roodolph Varca, Anthony C. Wu, Lei Marineau, Jason J. Smith, William B. Souza, Amanda Chory, Emma J. Armstrong, Scott A. Bradner, James E. TI Structure-Guided DOT1L Probe Optimization by Label-Free Ligand Displacement SO ACS CHEMICAL BIOLOGY LA English DT Article ID MIXED-LINEAGE LEUKEMIA; HISTONE METHYLTRANSFERASE DOT1L; H3K79 METHYLATION; INHIBITORS; POTENT; LEUKEMOGENESIS; CHROMATIN; CELLS AB The DOT1L lysine methyltransferase has emerged as a validated therapeutic target in MLL-rearranged (MLLr) acute leukemias. Although S-adenosylmethionine competitive inhibitors have demonstrated pharmacological proof-of-principle in MLLr-leukemia, these compounds require further optimization to improve cellular potency and pharmacokinetic stability. Limiting DOT1L inhibitor discovery and ligand optimization have been complex biochemical methods often using radionucleotides and cellular methods requiring prolonged culture. We therefore developed a new suite of assay technologies that allows comparative assessment of chemical tools for DOT1L in a miniaturized format. Coupling these assays with structural information, we developed new insights into DOT1L ligand binding and identified several functionalized probes with increased cellular potency (IC50 values similar to 10 nM) and excellent selectivity for DOT1L. Together these assay technologies define a platform capability for discovery and optimization of small-molecule DOT1L inhibitors. C1 [Yi, Joanna S.; Federation, Alexander J.; Qi, Jun; St Pierre, Roodolph; Varca, Anthony C.; Marineau, Jason J.; Smith, William B.; Souza, Amanda; Chory, Emma J.; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Yi, Joanna S.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Yi, Joanna S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Dhe-Paganon, Sirano] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Hadler, Michael; Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, Dept Pediat, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Xu, Xiang] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Wu, Lei] Shanghai ChemPartner Co Ltd, Shanghai, Peoples R China. RP Bradner, JE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM James_Bradner@dfci.harvard.edu FU U.S. National Institutes of Health [R01 CA176745]; William Lawrence & Blanche Hughes Foundation; Leukemia & Lymphoma Society SCOR; American Society of Hematology-Scholar Award FX We thank R. Paranal for his assistance in developing the high content assay; we thank C. Ott for helpful discussions and D. Buckley for thoughtful review of the manuscript. This work was funded by the U.S. National Institutes of Health grant R01 CA176745, the William Lawrence & Blanche Hughes Foundation, the Leukemia & Lymphoma Society SCOR grant, and the American Society of Hematology-Scholar Award. NR 23 TC 7 Z9 7 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 EI 1554-8937 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD MAR PY 2015 VL 10 IS 3 BP 667 EP 674 DI 10.1021/cb500796d PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CE1FY UT WOS:000351558700003 PM 25397901 ER PT J AU Iaconelli, J Huang, JH Berkovitch, SS Chattopadhyay, S Mazitschek, R Schreiber, SL Haggarty, SJ Karmacharya, R AF Iaconelli, Jonathan Huang, Joanne H. Berkovitch, Shaunna S. Chattopadhyay, Shrikanta Mazitschek, Ralph Schreiber, Stuart L. Haggarty, Stephen J. Karmacharya, Rakesh TI HDAC6 Inhibitors Modulate Lys49 Acetylation and Membrane Localization of beta-Catenin in Human iPSC-Derived Neuronal Cells SO ACS CHEMICAL BIOLOGY LA English DT Article ID CHROMATIN-MEDIATED NEUROPLASTICITY; HISTONE DEACETYLASE INHIBITORS; SYNAPTIC PLASTICITY; NUCLEAR-LOCALIZATION; MOUSE MODEL; PHOSPHORYLATION; PROTEIN; ACTIVATION; MECHANISMS; DISEASE AB We examined the effects of isoform-specific histone deacetylase (HDAC) inhibitors on beta-catenin posttranslational modifications in neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs). beta-catenin is a multifunctional protein with important roles in the developing and adult central nervous system. Activation of the Wnt pathway results in stabilization and nuclear translocation of beta-catenin, resulting in activation of multiple target genes. In addition, beta-catenin forms a complex with cadherins at the plasma membrane as part of the adherens junctions. The N-terminus of beta-catenin has phosphorylation, ubiquitination, and acetylation sites that regulate its stability and signaling. In the absence of a Wnt signal, Ser33, Ser37, and Thr41 are constitutively phosphorylated by glycogen synthase kinase 3 beta (GSK3 beta). beta-Catenin phosphorylated at these sites is recognized by beta-transducin repeat-containing protein (beta TrCP), which results in ubiquitination and degradation by the ubiquitin-proteasome pathway. The N-terminal regulatory domain of beta-catenin also includes Ser45, a phosphorylation site for Casein Kinase 1 alpha (CK1 alpha) and Lys49, which is acetylated by the acetyltransferase p300/CBP-associated factor (PCAF). The relevance of Lys49 acetylation and Ser45 phosphorylation to the function of beta-catenin is an active area of investigation. We find that HDAC6 inhibitors increase Lys49 acetylation and Ser45 phosphorylation but do not affect Ser33, Ser37, and Thr41 phosphorylation. Lys49 acetylation results in decreased ubiquitination of beta-catenin in the presence of proteasome inhibition. While increased Lys49 acetylation does not affect total levels of beta-catenin, it results in increased membrane localization of beta-catenin. C1 [Iaconelli, Jonathan; Huang, Joanne H.; Berkovitch, Shaunna S.; Haggarty, Stephen J.; Karmacharya, Rakesh] Harvard Univ, Ctr Human Genet Res, Ctr Expt Drugs & Diagnost, Psychiat & Neurodev Genet Unit,Med Sch, Boston, MA 02114 USA. [Iaconelli, Jonathan; Huang, Joanne H.; Berkovitch, Shaunna S.; Chattopadhyay, Shrikanta; Mazitschek, Ralph; Haggarty, Stephen J.; Karmacharya, Rakesh] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Iaconelli, Jonathan; Huang, Joanne H.; Berkovitch, Shaunna S.; Chattopadhyay, Shrikanta; Mazitschek, Ralph; Schreiber, Stuart L.; Karmacharya, Rakesh] Broad Inst Harvard & MIT, Ctr Sci Therapeut, Cambridge, MA 02142 USA. [Karmacharya, Rakesh] McLean Hosp, Schizophrenia & Bipolar Disorder Program, Belmont, MA 02478 USA. [Chattopadhyay, Shrikanta] Harvard Univ, MGH Canc Ctr, Sch Med, Boston, MA 02114 USA. [Mazitschek, Ralph] Harvard Univ, Ctr Syst Biol, Sch Med, Boston, MA 02114 USA. [Schreiber, Stuart L.] Harvard Univ, Howard Hughes Med Inst, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. RP Karmacharya, R (reprint author), Harvard Univ, Ctr Human Genet Res, Ctr Expt Drugs & Diagnost, Psychiat & Neurodev Genet Unit,Med Sch, Boston, MA 02114 USA. EM karmacharya@mcb.harvard.edu OI Haggarty, Stephen J./0000-0002-7872-168X FU National Institute of Mental Health Clinical Scientist Development Award [K08MH086846]; Brain and Behavior Research Foundation; Steve Willis and Elissa Freud; National Institute of General Medical Sciences Award [GM038627]; National Cancer Institute [P50CA086355]; National Institute of Mental Health [R33MH087896]; National Institute of Drug Abuse Award [R01DA028301] FX We thank S. Sheridan and B. Ghosh for helpful discussions, K. Hennig for technical assistance, and M. Bray for assistance with CellProfiler image analysis. This work was supported by the National Institute of Mental Health Clinical Scientist Development Award K08MH086846 (to R.K.), the Brain and Behavior Research Foundation Young Investigator Award (to R.K.), by Steve Willis and Elissa Freud (to R.K.), the National Institute of General Medical Sciences Award GM038627 (to S.L.S.), the National Cancer Institute Award P50CA086355 (to R.M.), the National Institute of Mental Health Award R33MH087896 (to S.J.H.), and the National Institute of Drug Abuse Award R01DA028301 (to S.J.H.). NR 57 TC 9 Z9 10 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 EI 1554-8937 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD MAR PY 2015 VL 10 IS 3 BP 883 EP 890 DI 10.1021/cb500838r PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CE1FY UT WOS:000351558700027 PM 25546293 ER PT J AU Lee, K Shao, HL Weissleder, R Lee, H AF Lee, Kyungheon Shao, Huilin Weissleder, Ralph Lee, Hakho TI Acoustic Purification of Extracellular Microvesicles SO ACS NANO LA English DT Article DE nanotechnology; microvesicles; nanoparticle separation; microfluidics; acoustic wave ID RED-BLOOD-CELLS; LARGE ONCOSOMES; VESICLES; EXOSOMES; MICROPARTICLES; SEPARATION; PARTICLES; THERAPY; WAVES AB Microvesicles (MVs) are an increasingly important source for biomarker discovery and clinical diagnostics. The small size of MVs and their presence in complex biological environment, however, pose technical challenges in sample preparation, particularly when sample volumes are small. We herein present an acoustic nanofilter system that size-specifically separates MVs in a continuous and contact-free manner. The separation uses ultrasound standing waves to exert differential acoustic force on MVs according to their size and density. By optimizing the design of the ultrasound transducers and underlying electronics, we were able to achieve a high separation yield and resolution. The "filter size-cutoff' can be controlled electronically in situ, which enables versatile MV-size selection. We applied the acoustic nanofilter to isolate nanoscale (<200 nm) vesicles from cell culture media as well as MVs in stored red blood cell products. With the capacity for rapid and contact-free MV isolation, the developed system could become a versatile preparatory tool for MV analyses. C1 [Lee, Kyungheon; Shao, Huilin; Weissleder, Ralph; Lee, Hakho] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Lee, H (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM hlee@mgh.harvard.edu RI Lee, Kyungheon/E-3863-2013 FU NIH [R01 HL113156, P01 CA069246, U54 CA151884]; DoD OCRP [W81XWH-14-1-0279]; Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2012R1A6A3A03040166] FX The authors thank X. O. Breakefield (Massachusetts General Hospital) for access to and assistance with the NTA. The acoustic device was fabricated using the facilities at the Center for Nanoscale Systems (CNS) at Harvard University (National Science Foundation award ECS-0335765). This work was supported in parts by NIH Grants R01 HL113156 (H.L.), P01 CA069246 (R.W.), U54 CA151884 (R.W.), and DoD OCRP Award W81XWH-14-1-0279 (H.L.). This research was also partially supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education 2012R1A6A3A03040166 (K.L.) NR 31 TC 27 Z9 27 U1 9 U2 56 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD MAR PY 2015 VL 9 IS 3 BP 2321 EP 2327 DI 10.1021/nn506538f PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA CE4HN UT WOS:000351791800010 PM 25672598 ER PT J AU Montgomerie, JZ Lawrence, AE LaMotte, AD Taft, CT AF Montgomerie, John Z. Lawrence, Amy E. LaMotte, Adam D. Taft, Casey T. TI The link between posttraumatic stress disorder and firearm violence: A review SO AGGRESSION AND VIOLENT BEHAVIOR LA English DT Review DE PTSD; Firearm; violence; Mental illness; Mass shooting ID NATIONAL COMORBIDITY SURVEY; DSM-IV DISORDERS; 3-YEAR FOLLOW-UP; SURVEY REPLICATION; VETERANS-AFFAIRS; POLICE OFFICERS; COMBAT VETERANS; PTSD SYMPTOMS; SUICIDE; SCHOOL AB The relationship between firearm violence and mental illness has been a longstanding issue, and one that has received recent national attention due to highly publicized shootings. However, no prior reviews have focused on the relationship between firearm violence and posttraumatic stress disorder (PTSD) specifically. The current review examines evidence of PTSD as both a consequence of and risk factor for firearm violence. The studies reviewed suggest elevated rates of PTSD among those exposed to firearm violence, with particularly high levels of PTSD found among witnesses of mass shootings and firearm injury survivors. Additionally, these studies indicate that certain factors, such as closer proximity to the incident and closer relationship to the victims, increase one's risk for developing PTSD. Although there is a dearth of research on PTSD as a risk factor for perpetration of firearm violence, the available evidence suggests a significant connection between the two. Gaps in the current literature are discussed, as well as directions for future study. Firearm violence remains a significant public health concern, and identifying its impacts and potential risk factors such as PTSD will be crucial for interventions aimed at addressing this problem. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Montgomerie, John Z.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA. [Lawrence, Amy E.; LaMotte, Adam D.; Taft, Casey T.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Taft, Casey T.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Montgomerie, JZ (reprint author), Univ So Calif, Keck Sch Med, 1975 Zonal Ave, Los Angeles, CA 90089 USA. EM Johnmont@usc.edu NR 59 TC 0 Z9 0 U1 4 U2 22 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-1789 EI 1873-6335 J9 AGGRESS VIOLENT BEH JI Aggress. Violent Behav. PD MAR-APR PY 2015 VL 21 BP 39 EP 44 DI 10.1016/j.avb.2015.01.009 PG 6 WC Criminology & Penology; Psychology, Multidisciplinary SC Criminology & Penology; Psychology GA CE4GW UT WOS:000351790100005 ER PT J AU Williston, SK Taft, CT VanHaasteren, KO AF Williston, Sarah Krill Taft, Casey T. VanHaasteren, Kayla O. TI Military veteran perpetrators of intimate partner violence: Challenges and barriers to coordinated intervention SO AGGRESSION AND VIOLENT BEHAVIOR LA English DT Article DE Veterans; Trauma; PTSD; Intimate partner violence; Diversion programs ID POSTTRAUMATIC-STRESS-DISORDER; DOMESTIC VIOLENCE; ANGER; AGGRESSION; CARE; INVOLVEMENT; DEPLOYMENT; PATTERNS; SOLDIERS; BEHAVIOR AB Intimate partner violence (IPV) is a significant concern among recently returning Veterans. In this paper, we discuss the etiology of IPV in this population and the intersections between Veteran healthcare and criminal justice system policies regarding Veteran IPV. We describe the current socio-political context in which clinical interventions and criminal justice diversion policies and pilot programs are emerging. Challenges to coordinating prevention and intervention across Veteran healthcare and criminal justice systems are discussed and highlighted via material on a Veteran-specific IPV intervention, and we discuss strategies for overcoming coordination challenges as well as areas for further innovation. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Williston, Sarah Krill] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. [Taft, Casey T.; VanHaasteren, Kayla O.] VA Boston Healthcare Syst, Behav Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. [Taft, Casey T.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP Williston, SK (reprint author), UMASS Boston, Dept Psychol, 100 Morrissey Blvd, Boston, MA 02125 USA. EM Sarah.Kri11001@umb.edu NR 47 TC 0 Z9 0 U1 3 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-1789 EI 1873-6335 J9 AGGRESS VIOLENT BEH JI Aggress. Violent Behav. PD MAR-APR PY 2015 VL 21 BP 55 EP 60 DI 10.1016/j.avb.2015.01.008 PG 6 WC Criminology & Penology; Psychology, Multidisciplinary SC Criminology & Penology; Psychology GA CE4GW UT WOS:000351790100007 ER PT J AU Yang, J Song, Y Wang, HX Liu, CN Li, ZZ Liu, Y Kong, YW AF Yang, Jing Song, Yang Wang, Hongxin Liu, Chunna Li, Zhongzhe Liu, Ying Kong, Yawei TI Insulin Treatment Prevents the Increase in D-Serine in Hippocampal CA1 Area of Diabetic Rats SO AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS LA English DT Article DE insulin; d-serine; long-term potentiation; water maze; serine racemase ID LONG-TERM POTENTIATION; MORRIS WATER MAZE; SYNAPTIC PLASTICITY; NMDA-RECEPTORS; SPATIAL MEMORY; AMINO-ACIDS; BRAIN; RACEMASE; MICE; GLUTAMATE AB Purpose: Diabetes is a high risk factor for dementia. Employing a diabetic rat model, the present study was designed to determine whether the content of d-serine (d-Ser) in hippocampus is associated with the impairment of spatial learning and memory ability. Methods: Diabetes was induced by a single intravenous injection of streptozotocin (STZ). The insulin treatment began 3 days after STZ injection. Results: We found that both water maze learning and hippocampal CA1 long-term potentiation (LTP) were impaired in diabetic rats. The contents of glutamate, d-Ser, and serine racemase in the hippocampus of diabetic rats were significantly higher than those in the control group. Insulin treatment prevented the STZ-induced impairment in water maze learning and hippocampal CA1-LTP in diabetic rats and also maintained the contents of glutamate, d-Ser, and serine racemase at the normal range in hippocampus. Conclusions: These results suggest that insulin treatment has a potent protection effect on CA1-LTP, spatial learning and memory ability of the diabetic rats in vivo. Furthermore, insulin may take effect by inhibiting the overactivation of N-methyl-d-aspartate receptors, which play a critical role in neurotoxicity. C1 [Yang, Jing; Song, Yang; Wang, Hongxin; Liu, Chunna; Li, Zhongzhe; Liu, Ying] Liaoning Med Univ, Prov Key Lab Cardiovasc & Cerebrovasc Drug Basic, Jinzhou 121001, Peoples R China. [Kong, Yawei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med,Div Plast & Reconstruct Surg, Boston, MA USA. RP Yang, J (reprint author), Liaoning Med Univ, Prov Key Lab Cardiovasc & Cerebrovasc Drug Basic, Jinzhou 121001, Peoples R China. EM yangjing@lnmu.edu.cn FU Liaoning Province science and technology plan project, China [2013225305] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the grant No. 2013225305 from Liaoning Province science and technology plan project, China. NR 42 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1533-3175 EI 1938-2731 J9 AM J ALZHEIMERS DIS JI Am. J. Alzheimers Dis. Other Dement. PD MAR PY 2015 VL 30 IS 2 BP 201 EP 208 DI 10.1177/1533317514545379 PG 8 WC Geriatrics & Gerontology; Clinical Neurology SC Geriatrics & Gerontology; Neurosciences & Neurology GA CE3EA UT WOS:000351707000012 PM 25118332 ER PT J AU Hsieh, YH Leung, FW AF Hsieh, Yu-Hsi Leung, Felix W. TI The Ideal Insertion Method for Colonoscopy Is in the Eye of the Beholder Response SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter ID MINIMALLY SEDATED COLONOSCOPY; CONTROLLED-TRIAL C1 [Hsieh, Yu-Hsi] Buddhist Tzu Chi Med Fdn, Dalin Tzu Chi Hosp, Dept Med, Div Gastroenterol, Chiayi 62247, Taiwan. [Hsieh, Yu-Hsi] Tzu Chi Univ, Sch Med, Hualien, Taiwan. [Leung, Felix W.] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, North Hill, CA USA. [Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Hsieh, YH (reprint author), Buddhist Tzu Chi Med Fdn, Dalin Tzu Chi Hosp, Dept Med, Div Gastroenterol, 2 Minsheng Rd, Chiayi 62247, Taiwan. EM hsieh.yuhsi@msa.hinet.net NR 5 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAR PY 2015 VL 110 IS 3 BP 475 EP 476 DI 10.1038/ajg.2015.15 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CE6AF UT WOS:000351917100022 PM 25743719 ER PT J AU Karaosmanoglu, AD Khawaja, RDA Onur, MR Kalra, MK AF Karaosmanoglu, Ali Devrim Khawaja, Ranish Deedar Ali Onur, Mehmet Ruhi Kalra, Mannudeep K. TI CT and MRI of Aortic Coarctation: Pre- and Postsurgical Findings SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE aortic coarctation; congenital heart disease; CT; MRI ID CONGENITAL HEART-DISEASE; ANGIOGRAPHY; ADULT; ECHOCARDIOGRAPHY; IMPLANTATION; MANAGEMENT; ANOMALIES; PREGNANCY; SPECTRUM AB OBJECTIVE. The purpose of this article is to summarize the roles of CT and MRI in the diagnosis and follow-up of patients with aortic coarctation. CONCLUSION. Aortic coarctation is a common congenital heart disease accounting for approximately 6-8% of congenital heart defects. Despite its deceptively simple anatomic presentation, it is a complex medical problem with several associated anatomic and physiologic abnormalities. CT and MRI may provide very accurate information of the coarctation anatomy and other associated cardiac abnormalities. C1 [Karaosmanoglu, Ali Devrim] Hacettepe Univ, Sch Med, Dept Radiol, Ankara, Turkey. [Khawaja, Ranish Deedar Ali; Kalra, Mannudeep K.] Massachusetts Gen Hosp, Div Cardiac Imaging, Boston, MA 02114 USA. [Khawaja, Ranish Deedar Ali; Kalra, Mannudeep K.] Harvard Univ, Sch Med, Boston, MA USA. [Onur, Mehmet Ruhi] Firat Univ, Sch Med, Dept Radiol, TR-23169 Elazig, Turkey. RP Karaosmanoglu, AD (reprint author), Hacettepe Univ, Sch Med, Dept Radiol, Ankara, Turkey. EM alidevrim76@yahoo.com NR 38 TC 0 Z9 0 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2015 VL 204 IS 3 BP W224 EP W233 DI 10.2214/AJR.14.12529 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CE1UU UT WOS:000351598800001 PM 25714305 ER PT J AU Krajewski, KM Nishino, M Ramaiya, NH Choueiri, TK AF Krajewski, Katherine M. Nishino, Mizuki Ramaiya, Nikhil H. Choueiri, Toni K. TI RECIST 1.1 Compared With RECIST 1.0 in Patients With Advanced Renal Cell Carcinoma Receiving Vascular Endothelial Growth Factor-Targeted Therapy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; renal cell carcinoma; Response Evaluation Criteria in Solid Tumors (RECIST); tumor response assessment; vascular endothelial growth factor-targeted therapy ID RESPONSE EVALUATION CRITERIA; ADVANCED GASTRIC-CANCER; GUIDELINE VERSION 1.1; COMPUTED-TOMOGRAPHY; TUMOR RESPONSE; SOLID TUMORS; ATTENUATION; SUNITINIB; EVALUATE; TRIAL AB OBJECTIVE. Response Evaluation Criteria in Solid Tumors (RECIST) is the most widely accepted method to objectively assess response to therapy in renal cell carcinoma (RCC) treated with vascular endothelial growth factor (VEGF)-targeted therapy. Both RECIST 1.0 and 1.1 have been used to assess response to VEGF-targeted therapies; however, systematic comparisons are lacking. MATERIALS AND METHODS. Sixty-two patients with metastatic RCC treated with VEGF-targeted therapies were retrospectively studied. Tumor measurements and response assessment according to RECIST 1.1 and RECIST 1.0 were compared, including the number of target lesions, baseline measurements, response at each follow-up, best overall response, and time to progression (TTP). Morphologic changes and new enhancement were also assessed over the course of treatment, and TTP was evaluated using morphologic change criteria in combination with RECIST 1.1. RESULTS. The number of target lesions according to RECIST 1.1 was significantly fewer than by RECIST 1.0 (median, 2 vs 4; p < 0.0001). At first imaging follow-up, the percentage change of the sums of the diameter measurements by RECIST 1.1 and RECIST 1.0 were highly concordant (R = 0.857; mean shrinkage, 12.1% by RECIST 1.1 vs 10.8% by RECIST 1.0). Best response assessment was highly concordant between the two criteria (weighted. = 0.819). There was no evidence of a difference in TTP by the two criteria, with a median TTP of 8.9 months (95% CI for the median, 5.5-13.9) by RECIST 1.1 and 8.9 months (95% CI for the median, 5.8-13.6) by RECIST 1.0. The median TTP by RECIST 1.1 alone was 8.9 months compared with 5.6 months for RECIST 1.1 and morphologic changes combined. CONCLUSION. RECIST 1.1 and RECIST 1.0 response assessments were overall highly concordant in patients with RCC treated with VEGF-targeted therapy, with fewer target lesions according to RECIST 1.1 but no difference in TTP. C1 [Krajewski, Katherine M.; Nishino, Mizuki; Ramaiya, Nikhil H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Imaging, Boston, MA 02115 USA. [Krajewski, Katherine M.; Nishino, Mizuki; Ramaiya, Nikhil H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Kidney Canc Ctr, Boston, MA 02115 USA. [Choueiri, Toni K.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Krajewski, KM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Imaging, 450 Brookline Ave, Boston, MA 02115 USA. EM kmkrajewski@partners.org FU GE Healthcare; Association of University Radiologists; National Cancer Institute [1K23CA157631]; Pfizer; Trust family; Loker Pinard; Michael Brigham funds for Kidney Cancer Research FX K. M. Krajewski received a research grant from GE Healthcare and the Association of University Radiologists. M. Nishino received support from the National Cancer Institute (grant 1K23CA157631). T. K. Choueiri serves on the advisory boards for Pfizer, Aveo, GlaxoSmithKline, and Novartis and has received research support from Pfizer, the Trust family, Loker Pinard, and Michael Brigham funds for Kidney Cancer Research. NR 27 TC 4 Z9 4 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2015 VL 204 IS 3 BP W282 EP W288 DI 10.2214/AJR.14.13236 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CE1UU UT WOS:000351598800009 PM 25714313 ER PT J AU Rehani, MM AF Rehani, Madan M. TI What Makes and Keeps Radiation Risks Associated With CT a Hot Topic? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material DE carcinogenic risks of CT; CT; radiation risks of CT; skin injuries in CT ID COMPUTED-TOMOGRAPHY C1 [Rehani, Madan M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rehani, Madan M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Rehani, MM (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM madan.rehani@gmail.com NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2015 VL 204 IS 3 BP W234 EP W235 DI 10.2214/AJR.14.12860 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CE1UU UT WOS:000351598800002 PM 25714306 ER PT J AU Tedeschi, V Rathmell, JP Eisenach, JC AF Tedeschi, Vicki Rathmell, James P. Eisenach, James C. TI Finding and Getting What You Want When You Want It Just Got Easier at Anesthesiology SO ANESTHESIOLOGY LA English DT Editorial Material C1 [Tedeschi, Vicki] Anesthesiol Editorial Off, Schaumburg, IL USA. [Rathmell, James P.] Harvard Med Syst, Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care Med, Boston, MA USA. [Eisenach, James C.] Wake Forest Sch Med, Dept Anesthesiol, Winston Salem, NC 27157 USA. RP Eisenach, JC (reprint author), Wake Forest Sch Med, Dept Anesthesiol, Winston Salem, NC 27157 USA. EM Editor-in-Chief@asahq.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD MAR PY 2015 VL 122 IS 3 BP 491 EP 494 DI 10.1097/ALN.0000000000000580 PG 4 WC Anesthesiology SC Anesthesiology GA CE3OY UT WOS:000351737900005 PM 25603458 ER PT J AU Parker, MJ Lovich, MA Tsao, AC Wei, AE Wakim, MG Maslov, MY Tsukada, H Peterfreund, RA AF Parker, Michael J. Lovich, Mark A. Tsao, Amy C. Wei, Abraham E. Wakim, Matthew G. Maslov, Mikhail Y. Tsukada, Hisashi Peterfreund, Robert A. TI Computer Control of Drug Delivery by Continuous Intravenous Infusion Bridging the Gap between Intended and Actual Drug Delivery SO ANESTHESIOLOGY LA English DT Article ID DEAD-VOLUME; IN-VITRO; DYNAMICS AB Background: Intravenous drug infusion driven by syringe pumps may lead to substantial temporal lags in achieving steady-state delivery at target levels when using very low flow rates (microinfusion). This study evaluated computer algorithms for reducing temporal lags via coordinated control of drug and carrier flows. Methods: Novel computer control algorithms were developed based on mathematical models of fluid flow. Algorithm 1 controlled initiation of drug infusion and algorithm 2 controlled changes to ongoing steady-state infusions. These algorithms were tested in vitro and in vivo using typical high and low dead volume infusion system architectures. One syringe pump infused a carrier fluid and a second infused drug. Drug and carrier flowed together via a manifold through standard central venous catheters. Samples were collected in vitro for quantitative delivery analysis. Parameters including left ventricular max dP/dt were recorded in vivo. Results: Regulation by algorithm 1 reduced delivery delay in vitro during infusion initiation by 69% (low dead volume) and 78% (high dead volume). Algorithmic control in vivo measuring % change in max dP/dt showed similar results (55% for low dead volume and 64% for high dead volume). Algorithm 2 yielded greater precision in matching the magnitude and timing of intended changes in vivo and in vitro. Conclusions: Compared with conventional methods, algorithm-based computer control of carrier and drug flows can improve drug delivery by pump-driven intravenous infusion to better match intent. For norepinephrine infusions, the amount of drug reaching the bloodstream per time appears to be a dominant factor in the hemodynamic response to infusion. C1 [Parker, Michael J.] Beth Israel Deaconess Med Ctr, Dept Med, Div Pulm Crit Care & Sleep Med, Boston, MA 02215 USA. [Lovich, Mark A.; Wei, Abraham E.; Wakim, Matthew G.; Maslov, Mikhail Y.] Steward St Elizabeths Med Ctr, Dept Anesthesiol & Pain Med, Boston, MA USA. [Tsukada, Hisashi] Steward St Elizabeths Med Ctr, Dept Med, Div Pulmonol, Boston, MA USA. [Tsao, Amy C.; Peterfreund, Robert A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Parker, MJ (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Pulm Crit Care & Sleep Med,Dept Med, 25 Shattuck St,Room 307D, Boston, MA 02115 USA. EM michael_parker@hms.harvard.edu NR 11 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD MAR PY 2015 VL 122 IS 3 BP 647 EP 658 DI 10.1097/ALN.0000000000000519 PG 12 WC Anesthesiology SC Anesthesiology GA CE3OY UT WOS:000351737900018 PM 25419684 ER PT J AU Mauck, RL Burdick, JA AF Mauck, Robert L. Burdick, Jason A. TI From Repair to Regeneration: Biomaterials to Reprogram the Meniscus Wound Microenvironment SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE Meniscus; Biomaterials; Wound healing; Regeneration; Scaffold; Extracellular matrix ID STEM-CELL DIFFERENTIATION; NECROSIS-FACTOR-ALPHA; HUMAN KNEE-JOINT; IN-VITRO; NUCLEAR MECHANICS; HYALURONIC-ACID; SYNOVIAL-FLUID; 3-DIMENSIONAL HYDROGELS; NANOFIBROUS SCAFFOLDS; PARTIAL MENISCECTOMY AB When the field of tissue engineering first arose, scaffolds were conceived of as inert three-dimensional structures whose primary function was to support cellularity and tissue growth. Since then, advances in scaffold and biomaterial design have evolved to not only guide tissue formation, but also to interact dynamically with and manipulate the wound environment. At present, these efforts are being directed towards strategies that directly address limitations in endogenous wound repair, with the goal of reprogramming the local wound environment (and the cells within that locality) from a state that culminates in an inferior tissue repair into a state in which functional regeneration is achieved. This review will address this approach with a focus on recent advances in scaffold design towards the resolution of tears of the knee meniscus as a case example. The inherent limitations to endogenous repair will be discussed, as will specific examples of how biomaterials are being designed to overcome these limitations. Examples will include design of fibrous scaffolds that promote colonization by modulating local extracellular matrix density and delivering recruitment factors. Furthermore, we will discuss scaffolds that are themselves modulated by the wound environment to alter porosity and modulate therapeutic release through precise coordination of scaffold degradation. Finally, we will close with emerging concepts in local control of cell mechanics to improve interstitial cell migration and so advance repair. Overall, these examples will illustrate how emergent features within a biomaterial can be tuned to manipulate and harness the local tissue microenvironment in order to promote robust regeneration. C1 [Mauck, Robert L.] Univ Penn, McKay Orthopaed Res Lab, Dept Orthopaed Surg, Perelman Sch Med, Philadelphia, PA 19104 USA. [Burdick, Jason A.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. [Mauck, Robert L.; Burdick, Jason A.] Philadelphia VA Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA. RP Mauck, RL (reprint author), Univ Penn, McKay Orthopaed Res Lab, Dept Orthopaed Surg, Perelman Sch Med, 424 Stemmler Hall,36th St & Hamilton Walk, Philadelphia, PA 19104 USA. EM lemauck@mail.med.upenn.edu; burdick2@seas.upenn.edu FU National Institutes of Health [R01 EB008722, AR056624]; Department of Veterans Affairs [I01 RX000700, RX000174] FX This work was supported with grants from the National Institutes of Health (R01 EB008722 and AR056624) and the Department of Veterans Affairs (I01 RX000700 and RX000174). The authors gratefully acknowledge Dr. Brendon Baker, Dr. Matt Fisher, Dr. Lara Ionescu, Dr. Iris Kim, Dr. Brendan Purcell, and Ms. Feini (Sylvia) Qu for their helpful input, graphical design, and in depth discussions on this topic. NR 122 TC 9 Z9 9 U1 3 U2 29 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 EI 1573-9686 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD MAR PY 2015 VL 43 IS 3 BP 529 EP 542 DI 10.1007/s10439-015-1249-z PG 14 WC Engineering, Biomedical SC Engineering GA CE3QF UT WOS:000351742500005 PM 25650096 ER PT J AU Davids, MS Kim, H Costello, C Avigan, D Chen, YB Armand, P Alyea, EP Hedlund, J McSweeney, P Liguori, R Ritz, J Ball, E Bashey, A Soiffer, R AF Davids, M. S. Kim, H. Costello, C. Avigan, D. Chen, Y. B. Armand, P. Alyea, E. P. Hedlund, J. McSweeney, P. Liguori, R. Ritz, J. Ball, E. Bashey, A. Soiffer, R. CA Blood Canc Res Partnership TI Interim results of a multicenter phase I/Ib study of CTLA4 blockade with ipilimumab for relapsed hematologic malignancies after allogeneic hematopoietic cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation CY MAR 22-25, 2015 CL Istanbul, TURKEY SP European Soc Blood & Marrow Transplantat C1 [Davids, M. S.; Kim, H.; Armand, P.; Alyea, E. P.; Liguori, R.; Ritz, J.; Soiffer, R.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Costello, C.; Ball, E.] Univ Calif San Diego, Moores Canc Ctr, Div BMT, La Jolla, CA 92093 USA. [Avigan, D.] Beth Israel Deaconess Med Ctr, BMT Program, Boston, MA 02215 USA. [Chen, Y. B.] Massachusetts Gen Hosp, Ctr Canc, BMT Program, Boston, MA USA. [Hedlund, J.] New England Canc Specialists, Maine Ctr Canc Med, Scarborough, ME USA. [McSweeney, P.] Colorado Blood Canc Inst, Denver, CO USA. [Bashey, A.] Northside Hosp, Blood & Marrow Transplant Grp Georgia, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2015 VL 50 SU 1 MA O141 BP S82 EP S82 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA CE2GN UT WOS:000351632900142 ER PT J AU Kekre, N Kim, H Thanarajasingam, G Armand, P Antin, J Cutler, C Nikiforow, S Ho, V Alyea, E Koreth, J Soiffer, R AF Kekre, N. Kim, H. Thanarajasingam, G. Armand, P. Antin, J. Cutler, C. Nikiforow, S. Ho, V. Alyea, E. Koreth, J. Soiffer, R. TI Immunosuppression Taper as the Sole Therapy for Early Relapse is Effective after Reduced Intensity Allogeneic Hematopoietic Cell Transplantation SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation CY MAR 22-25, 2015 CL Istanbul, TURKEY SP European Soc Blood & Marrow Transplantat C1 [Kekre, N.; Kim, H.; Armand, P.; Antin, J.; Cutler, C.; Nikiforow, S.; Ho, V.; Alyea, E.; Koreth, J.; Soiffer, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Thanarajasingam, G.] Mayo Clin, Rochester, MN USA. NR 0 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 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2015 VL 50 SU 1 MA P667 BP S453 EP S454 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA CE2GN UT WOS:000351632902280 ER PT J AU Khera, N Albelda, R Hahn, T Salas-Coronado, D Marcellot, L Tucker-Seeley, R Odejide, O Soiffer, R Abel, G AF Khera, N. Albelda, R. Hahn, T. Salas-Coronado, D. Marcellot, L. Tucker-Seeley, R. Odejide, O. Soiffer, R. Abel, G. TI Association of Psycho social Outcomes with Familial Financial Hardship after Hematopoietic Cell Transplantation SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation CY MAR 22-25, 2015 CL Istanbul, TURKEY SP European Soc Blood & Marrow Transplantat C1 [Khera, N.] Mayo Clin, Phoenix, AZ USA. [Albelda, R.] Univ Massachusetts, Boston, MA 02125 USA. [Hahn, T.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Salas-Coronado, D.; Marcellot, L.; Tucker-Seeley, R.; Odejide, O.; Soiffer, R.; Abel, G.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2015 VL 50 SU 1 MA P606 BP S423 EP S423 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA CE2GN UT WOS:000351632902219 ER PT J AU Khera, N Chai, X Duong, H Inamoto, Y Chen, G Mayer, S Arora, M Palmer, J Flowers, M Cutler, C Lukez, A Arai, S Lazaryan, A Pusic, I Krupski, MC Wood, W Lee, S Pidala, J AF Khera, N. Chai, X. Duong, H. Inamoto, Y. Chen, G. Mayer, S. Arora, M. Palmer, J. Flowers, M. Cutler, C. Lukez, A. Arai, S. Lazaryan, A. Pusic, I. Krupski, M. C. Wood, W. Lee, S. Pidala, J. TI Prospective Longitudinal Study of Late Acute Graft Versus Host Disease after Hematopoietic Cell Transplantation: A Report from Chronic GVHD Consortium SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation CY MAR 22-25, 2015 CL Istanbul, TURKEY SP European Soc Blood & Marrow Transplantat C1 [Khera, N.; Palmer, J.] Mayo Clin, Phoenix, AZ USA. [Chai, X.; Flowers, M.; Lee, S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Duong, H.] Cleveland Clin, Cleveland, OH 44106 USA. [Inamoto, Y.] Natl Canc Ctr, Tokyo, Japan. [Chen, G.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Mayer, S.] Weill Cornell Med Coll, New York, NY USA. [Arora, M.; Lazaryan, A.] Univ Minnesota, Minneapolis, MN USA. [Cutler, C.; Lukez, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Arai, S.] Stanford Univ, Palo Alto, CA 94304 USA. [Pusic, I.] Washington Univ, St Louis, MO 63130 USA. [Krupski, M. C.] Vanderbilt Univ, Nashville, TN 37235 USA. [Wood, W.] Univ N Carolina, Chapel Hill, NC USA. [Pidala, J.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. NR 0 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 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2015 VL 50 SU 1 MA P528 BP S384 EP S385 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA CE2GN UT WOS:000351632902143 ER PT J AU Kim, JW Lee, J Kim, BS Chong, SY Jung, CW Kim, YK Mun, YC Jo, DY Lee, HG Won, JH Park, JS Lee, JH Moon, JH Do, YR Cheong, JW Lee, JH Yhim, HY Kim, H Yoon, SS AF Kim, J. -W. Lee, J. Kim, B. -S. Chong, S. Y. Jung, C. W. Kim, Y. -K. Mun, Y. -C. Jo, D. -Y. Lee, H. G. Won, J. -H. Park, J. S. Lee, J. H. Moon, J. H. Do, Y. R. Cheong, J. -W. Lee, J. -H. Yhim, H. -Y. Kim, H. Yoon, S. -S. CA Korean Soc Blood Marrow TI Impact of stem cell dose and performance status on cord blood transplantation outcome in adult patients with advanced hematologic diseases: 13-year experience in Korea SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation CY MAR 22-25, 2015 CL Istanbul, TURKEY SP European Soc Blood & Marrow Transplantat C1 [Kim, J. -W.; Yoon, S. -S.] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. [Lee, J.; Kim, B. -S.] Daegu Fatima Hosp, Dept Internal Med, Daegu, South Korea. [Chong, S. Y.] Bundang CHA Hosp, Dept Internal Med, Songnam, South Korea. [Jung, C. W.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Internal Med, Seoul, South Korea. [Kim, Y. -K.] Chonnam Natl Univ, Hwasun Hosp, Dept Internal Med, Gwangju, South Korea. [Mun, Y. -C.] Ewha Womans Univ, Mokdong Hosp, Dept Internal Med, Seoul, South Korea. [Jo, D. -Y.] Chungnam Natl Univ Hosp, Dept Internal Med, Taejon, South Korea. [Lee, H. G.] Konkuk Univ Hosp, Dept Internal Med, Seoul, South Korea. [Won, J. -H.] Soon Chun Hyang Univ Hosp, Dept Internal Med, Seoul, South Korea. [Park, J. S.] Ajou Univ Hosp, Dept Internal Med, Suwon, South Korea. [Lee, J. H.] Gachon Univ, Gil Hosp, Dept Internal Med, Inchon, South Korea. [Moon, J. H.] Kyungpook Natl Univ Hosp, Dept Internal Med, Daegu, South Korea. [Do, Y. R.] Dongsan Med Ctr, Dept Internal Med, Daegu, South Korea. [Cheong, J. -W.] Yonsei Univ, Severance Hosp, Dept Internal Med, Seoul 120749, South Korea. [Lee, J. -H.] Asan Med Ctr, Dept Internal Med, Seoul, South Korea. [Yhim, H. -Y.] Chonbuk Natl Univ Hosp, Dept Internal Med, Jeonju, South Korea. [Kim, H.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. NR 0 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 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2015 VL 50 SU 1 MA P465 BP S354 EP S355 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA CE2GN UT WOS:000351632902083 ER PT J AU Kotsiou, E Guinan, E Gribben, J Davies, J AF Kotsiou, E. Guinan, E. Gribben, J. Davies, J. TI Phenotypic and functional stability of regulatory T cells expanded after alloanergization with costimulatory molecule blockade SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation CY MAR 22-25, 2015 CL Istanbul, TURKEY SP European Soc Blood & Marrow Transplantat C1 [Kotsiou, E.; Gribben, J.; Davies, J.] Barts Canc Inst, Ctr Hematooncol, London, England. [Guinan, E.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Guinan, E.] Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. [Guinan, E.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 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 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2015 VL 50 SU 1 MA P502 BP S373 EP S373 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA CE2GN UT WOS:000351632902120 ER PT J AU Madenci, AL Stetson, A Weldon, C Lehmann, L AF Madenci, A. L. Stetson, A. Weldon, C. Lehmann, L. TI Safety of peritoneal and pleural drain placement in pediatric stem cell transplant recipients with severe veno-occlusive disease SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation CY MAR 22-25, 2015 CL Istanbul, TURKEY SP European Soc Blood & Marrow Transplantat C1 [Madenci, A. L.; Weldon, C.] Boston Childrens Hosp, Dept Surg, Boston, MA USA. [Madenci, A. L.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Stetson, A.; Weldon, C.; Lehmann, L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Lehmann, L.] Boston Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA USA. NR 0 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 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2015 VL 50 SU 1 MA P256 BP S244 EP S245 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA CE2GN UT WOS:000351632901251 ER PT J AU Nicolini, FE DeAngelo, DJ Abruzzese, E Apperley, JF Holyoake, TL Larson, RA Lustgarten, S Rivera, VM Clackson, T Conlon, MG Haluska, FG Talpaz, M Cortes, JE AF Nicolini, F. E. DeAngelo, D. J. Abruzzese, E. Apperley, J. F. Holyoake, T. L. Larson, R. A. Lustgarten, S. Rivera, V. M. Clackson, T. Conlon, M. G. Haluska, F. G. Talpaz, M. Cortes, J. E. TI Ponatinib for Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph plus ALL) With History of Stem Cell Transplantation (SCT): Efficacy and Safety Results of the PACE Trial SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation CY MAR 22-25, 2015 CL Istanbul, TURKEY SP European Soc Blood & Marrow Transplantat C1 [Nicolini, F. E.] Ctr Hosp Lyon Sud, F-69310 Pierre Benite, France. [DeAngelo, D. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Abruzzese, E.] Univ Roma Tor Vergata, S Eugenio Hosp, Rome, Italy. [Apperley, J. F.] Univ London Imperial Coll Sci Technol & Med, Ctr Haematol, London, England. [Holyoake, T. L.] Univ Glasgow, Inst Canc Sci, Paul OGorman Leukaemia Res Ctr, Glasgow, Lanark, Scotland. [Larson, R. A.] Univ Chicago, Chicago, IL 60637 USA. [Lustgarten, S.; Rivera, V. M.; Clackson, T.; Conlon, M. G.; Haluska, F. G.] ARIAD Pharmaceut Inc, Cambridge, MA USA. [Talpaz, M.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Cortes, J. E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RI Holyoake, Tessa/M-3668-2015 OI Holyoake, Tessa/0000-0002-0608-6066 NR 0 TC 0 Z9 0 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2015 VL 50 SU 1 MA P744 BP S490 EP S490 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA CE2GN UT WOS:000351632902352 ER PT J AU Richardson, PG Smith, AR Triplett, BM Kernan, NA Grupp, SA Antin, JH Lehmann, L Miloslavsky, M Hume, R Hannah, AL Nejadnik, B Soiffer, RJ AF Richardson, P. G. Smith, A. R. Triplett, B. M. Kernan, N. A. Grupp, S. A. Antin, J. H. Lehmann, L. Miloslavsky, M. Hume, R. Hannah, A. L. Nejadnik, B. Soiffer, R. J. TI Defibrotide for Pediatric and Adult Patients with Hepatic Veno-occlusive Disease: Interim Age Subgroup Survival Analysis From an Ongoing Expanded Access Program in the US SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation CY MAR 22-25, 2015 CL Istanbul, TURKEY SP European Soc Blood & Marrow Transplantat C1 [Richardson, P. G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancy,Dept Med Oncol,Jerome Lipp, Boston, MA 02115 USA. [Smith, A. R.] Univ Minnesota, Div Pediat Blood & Marrow Transplantat, Minneapolis, MN USA. [Triplett, B. M.] St Jude Childrens Res Hosp, Bone Marrow Transplantat & Cellular Therapy, Memphis, TN 38105 USA. [Kernan, N. A.] Mem Sloan Kettering Canc Ctr, Pediat BMT Serv, New York, NY 10021 USA. [Grupp, S. A.] Childrens Hosp Philadelphia, Pediat Oncol, Philadelphia, PA 19104 USA. [Antin, J. H.; Soiffer, R. J.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Stem Cell Bone Marrow Transplantat Program,Div He, Boston, MA 02115 USA. [Lehmann, L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancy,Dept Med Oncol,Ctr Stem Ce, Boston, MA 02115 USA. [Miloslavsky, M.; Hume, R.; Hannah, A. L.; Nejadnik, B.] Jazz Pharmaceut Inc, Palo Alto, CA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2015 VL 50 SU 1 MA O127 BP S74 EP S75 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA CE2GN UT WOS:000351632900128 ER PT J AU Richardson, PG Smith, AR Triplett, BM Kernan, NA Grupp, SA Antin, JH Lehmann, L Miloslavsky, M Hume, R Hannah, AL Nejadnik, B Soiffer, RJ AF Richardson, P. G. Smith, A. R. Triplett, B. M. Kernan, N. A. Grupp, S. A. Antin, J. H. Lehmann, L. Miloslavsky, M. Hume, R. Hannah, A. L. Nejadnik, B. Soiffer, R. J. TI Defibrotide for Hepatic Veno-Occlusive Disease Following Allogeneic or Autologous Hematopoietic Stem Cell Transplant: Interim Subgroup Survival Analysis From an Ongoing US Study SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation CY MAR 22-25, 2015 CL Istanbul, TURKEY SP European Soc Blood & Marrow Transplantat C1 [Richardson, P. G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancy,Dept Med Oncol,Jerome Lipp, Boston, MA 02115 USA. [Smith, A. R.] Univ Minnesota, Div Pediat Blood & Marrow Transplantat, Minneapolis, MN USA. [Triplett, B. M.] St Jude Childrens Res Hosp, Bone Marrow Transplantat & Cellular Therapy, Memphis, TN 38105 USA. [Kernan, N. A.] Mem Sloan Kettering Canc Ctr, Pediat BMT Serv, New York, NY 10021 USA. [Grupp, S. A.] Childrens Hosp Philadelphia, Pediat Oncol, Philadelphia, PA 19104 USA. [Antin, J. H.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Stem Cell Bone Marrow Transplantat Program,Div He, Boston, MA 02115 USA. [Lehmann, L.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Ctr Stem Cell Transplantat,Div Hematol Malignancy, Boston, MA 02115 USA. [Miloslavsky, M.; Hume, R.; Hannah, A. L.; Nejadnik, B.; Soiffer, R. J.] Jazz Pharmaceut Inc, Palo Alto, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2015 VL 50 SU 1 MA O058 BP S34 EP S35 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA CE2GN UT WOS:000351632900059 ER PT J AU Vij, R Hars, V Blum, W Shore, T Rapoport, A Shea, T Hoke, E Stone, R Friedman, P Owzar, K Devine, S AF Vij, R. Hars, V. Blum, W. Shore, T. Rapoport, A. Shea, T. Hoke, E. Stone, R. Friedman, P. Owzar, K. Devine, S. TI CALGB 100801 (Alliance): A phase II multi-center study of azacitidine (AZA) following allogeneic transplantation using a "test dose'' targeted busulfan conditioning regimen for high risk myelodysplasia and older patients with acute myeloid leukemia SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation CY MAR 22-25, 2015 CL Istanbul, TURKEY SP European Soc Blood & Marrow Transplantat C1 [Vij, R.] Washington Univ, Sect BMT & Leukemia, Sch Med, St Louis, MO 63130 USA. [Hars, V.; Hoke, E.] Duke Univ, Alliance Stat & Data Ctr, Durham, NC 27706 USA. [Blum, W.; Devine, S.] Ohio State Univ, Columbus, OH 43210 USA. [Shore, T.] Weill Med Coll, New York, NY USA. [Rapoport, A.] Univ Maryland, Baltimore, MD 21201 USA. [Shea, T.] Univ N Carolina, Chapel Hill, NC USA. [Stone, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Friedman, P.] Univ Chicago, Chicago, IL 60637 USA. [Owzar, K.] Alliance Stat & Data Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2015 VL 50 SU 1 MA P640 BP S440 EP S441 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA CE2GN UT WOS:000351632902253 ER PT J AU Yuan, A Chai, X Martins, F Cutler, C Lee, S Treister, N AF Yuan, A. Chai, X. Martins, F. Cutler, C. Lee, S. Treister, N. TI Oral chronic graft-versus-host disease outcomes and resource utilization: a subanalysis from the chronic GVHD Consortium SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation CY MAR 22-25, 2015 CL Istanbul, TURKEY SP European Soc Blood & Marrow Transplantat C1 [Yuan, A.; Treister, N.] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02115 USA. [Yuan, A.; Treister, N.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Chai, X.; Lee, S.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Martins, F.] Univ Sao Paulo, Sch Dent, Dept Oral Pathol, Sao Paulo, Brazil. [Cutler, C.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. NR 1 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 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2015 VL 50 SU 1 MA P092 BP S162 EP S163 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA CE2GN UT WOS:000351632901088 ER PT J AU Burstein, HJ AF Burstein, H. J. TI Endocrine therapy for post-menopausal patients: type and duration SO BREAST LA English DT Meeting Abstract ID ADJUVANT TAMOXIFEN; METAANALYSIS; TRIALS C1 [Burstein, H. J.] Harvard Univ, Sch Med, Breast Oncol Ctr, Dana Farber Canc Inst, Boston, MA USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 EI 1532-3080 J9 BREAST JI Breast PD MAR PY 2015 VL 24 SU 1 MA PG 11.02 BP S21 EP S22 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CE4IT UT WOS:000351795000040 ER PT J AU Garber, J AF Garber, J. TI Using germline genetics in the management of breast cancer patients and their families SO BREAST LA English DT Meeting Abstract C1 [Garber, J.] Dana Farber Canc Inst, Ctr Canc Genet & Prevent, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 EI 1532-3080 J9 BREAST JI Breast PD MAR PY 2015 VL 24 SU 1 MA PG 6.01 BP S10 EP S11 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CE4IT UT WOS:000351795000021 ER PT J AU Partridge, A AF Partridge, A. TI Management of breast cancer in very young women SO BREAST LA English DT Meeting Abstract C1 [Partridge, A.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 EI 1532-3080 J9 BREAST JI Breast PD MAR PY 2015 VL 24 SU 1 MA PG 13.01 BP S24 EP S24 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CE4IT UT WOS:000351795000046 ER PT J AU Regan, M AF Regan, M. TI Predicting benefit of endocrine therapy SO BREAST LA English DT Meeting Abstract C1 [Regan, M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 EI 1532-3080 J9 BREAST JI Breast PD MAR PY 2015 VL 24 SU 1 MA PG 11.03 BP S22 EP S22 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CE4IT UT WOS:000351795000041 ER PT J AU Winer, E AF Winer, E. TI Tailoring the chemotherapy regimen in patients with triple negative subtypes SO BREAST LA English DT Meeting Abstract C1 [Winer, E.] Dana Farber Canc Inst, Div Womens Canc, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 EI 1532-3080 J9 BREAST JI Breast PD MAR PY 2015 VL 24 SU 1 MA PG 12.01 BP S22 EP S22 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CE4IT UT WOS:000351795000042 ER PT J AU Javidi-Sharifi, N Traer, E Martinez, J Gupta, A Taguchi, T Dunlap, J Heinrich, MC Corless, CL Rubin, BP Druker, BJ Tyner, JW AF Javidi-Sharifi, Nathalie Traer, Elie Martinez, Jacqueline Gupta, Anu Taguchi, Takehiro Dunlap, Jennifer Heinrich, Michael C. Corless, Christopher L. Rubin, Brian P. Druker, Brian J. Tyner, Jeffrey W. TI Crosstalk between KIT and FGFR3 Promotes Gastrointestinal Stromal Tumor Cell Growth and Drug Resistance SO CANCER RESEARCH LA English DT Article ID PROSTATE-CANCER; FACTOR RECEPTOR-3; LUNG-CANCER; B-RAF; SURVIVAL; LEUKEMIA; IMATINIB; MUTATION; KINASE; MECHANISMS AB Kinase inhibitors such as imatinib have dramatically improved outcomes for patients with gastrointestinal stromal tumor (GIST), but many patients develop resistance to these treatments. Although in some patients this event corresponds with mutations in the GIST driver oncogenic kinase KIT, other patients develop resistance without KIT mutations. In this study, we address this patient subset in reporting a functional dependence of GIST on the FGF receptor FGFR3 and its crosstalk with KIT in GIST cells. Addition of the FGFR3 ligand FGF2 to GIST cells restored KIT phosphorylation during imatinib treatment, allowing sensitive cells to proliferate in the presence of the drug. FGF2 expression was increased in imatinib-resistant GIST cells, the growth of which was blocked by RNAi-mediated silencing of FGFR3. Moreover, combining KIT and FGFR3 inhibitors synergized to block the growth of imatinib-resistant cells. Signaling crosstalk between KIT and FGFR3 activated the MAPK pathway to promote resistance to imatinib. Clinically, an IHC analysis of tumor specimens from imatinib-resistant GIST patients revealed a relative increase in FGF2 levels, with a trend toward increased expression in imatinib-naive samples consistent with possible involvement in drug resistance. Our findings provide a mechanistic rationale to evaluate existing FGFR inhibitors and multikinase inhibitors that target FGFR3 as promising strategies to improve treatment of patients with GIST with de novo or acquired resistance to imatinib. (C)2014 AACR. C1 [Javidi-Sharifi, Nathalie; Traer, Elie; Martinez, Jacqueline; Dunlap, Jennifer; Heinrich, Michael C.; Corless, Christopher L.; Druker, Brian J.; Tyner, Jeffrey W.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. [Javidi-Sharifi, Nathalie; Traer, Elie; Heinrich, Michael C.; Druker, Brian J.] Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland, OR 97239 USA. [Gupta, Anu; Rubin, Brian P.] Lerner Res Inst, Dept Mol Genet, Cleveland, OH USA. [Taguchi, Takehiro] Kochi Univ, Grad Sch Kuroshio Sci, Div Human Hlth & Med Sci, Nankoku, Kochi, Japan. [Dunlap, Jennifer; Corless, Christopher L.] Oregon Hlth & Sci Univ, Depat Anat Pathol, Portland, OR 97239 USA. [Heinrich, Michael C.] Portland VA Med Ctr, Portland, OR USA. [Rubin, Brian P.] Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA. [Rubin, Brian P.] Cleveland Clin, Dept Anat Pathol, Cleveland, OH 44106 USA. [Druker, Brian J.] Howard Hughes Med Inst, Portland, OR USA. [Tyner, Jeffrey W.] Oregon Hlth & Sci Univ, Dept Cell Dev & Canc Biol, Portland, OR 97239 USA. RP Tyner, JW (reprint author), Oregon Hlth & Sci Univ, Knight Canc Inst, 3181 Southwest Sam Jackson Pk Rd,Mailcode L592, Portland, OR 97239 USA. EM tynerj@ohsu.edu FU Oregon Clinical and Translational Research Institute (OCTRI); National Center for Advancing Translational Sciences (NCATS) [TL1 RR024159]; NIH; NIH Roadmap for Medical Research; V Foundation for Cancer Research; Leukemia and Lymphoma Society; Gabrielle's Angel Foundation for Cancer Research; National Cancer Institute [5R00CA151457-04, 1R01CA183974-01]; Life Raft Group FX N. Javidi-Sharifi was supported by the Oregon Clinical and Translational Research Institute (OCTRI), grant number TL1 RR024159 from the National Center for Advancing Translational Sciences (NCATS), a component of the NIH, and NIH Roadmap for Medical Research. B.J. Druker was an investigator of the Howard Hughes Medical Institute. J.W. Tyner was supported by grants from the V Foundation for Cancer Research, The Leukemia and Lymphoma Society, the Gabrielle's Angel Foundation for Cancer Research, and the National Cancer Institute (5R00CA151457-04; 1R01CA183974-01). B.P. Rubin and A. Gupta were supported by the Life Raft Group. NR 34 TC 15 Z9 15 U1 2 U2 10 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 MAR 1 PY 2015 VL 75 IS 5 BP 880 EP 891 DI 10.1158/0008-5472.CAN-14-0573 PG 12 WC Oncology SC Oncology GA CE6GG UT WOS:000351934100012 PM 25432174 ER PT J AU Sepulcre, J AF Sepulcre, Jorge TI An OP4 Functional Stream in the Language-Related Neuroarchitecture SO CEREBRAL CORTEX LA English DT Article DE auditory-motor (A M) interface; functional connectivity; graph theory; language; network ID HUMAN BRAIN; CEREBRAL-CORTEX; SPEECH ARTICULATION; ARCUATE FASCICULUS; CORTICAL NETWORK; AUDITORY-CORTEX; CONNECTIVITY; ORGANIZATION; PATHWAYS; AREAS AB Sensory comprehension and motor production of language symbols form the basis of human speech. Classical neuroanatomy has pointed to Wernicke's and Broca's areas as playing important roles in the integration of these 2 functions. However, recent studies have proposed that more direct pathways may exist between auditory input and motor output, bypassing Wernicke's and Broca's areas. We used functional network analyses to investigate potential auditorymotor (A-M) couplings between language-related cortices. We found that operculum parietale (OP) interconnectivity in region OP-4 seems to play a critical role in the A-M integration of the brain. This finding supports a novel landscape in the functional neuroarchitecture that sustains language in humans. C1 [Sepulcre, Jorge] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Sepulcre, Jorge] Harvard Univ, Sch Med, Boston, MA USA. [Sepulcre, Jorge] Massachusetts Gen Hosp, Athinioula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Sepulcre, Jorge] Harvard Univ, Sch Med, Charlestown, MA USA. RP Sepulcre, J (reprint author), Harvard Univ, 52 Oxford St,Northwest Bldg,280-02, Cambridge, MA 02138 USA. EM sepulcre@nmr.mgh.harvard.edu NR 66 TC 5 Z9 5 U1 2 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD MAR PY 2015 VL 25 IS 3 BP 658 EP 666 DI 10.1093/cercor/bht256 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CE6GW UT WOS:000351935800008 PM 24084124 ER PT J AU Pascual, B Masdeu, JC Hollenbeck, M Makris, N Insausti, R Ding, SL Dickerson, BC AF Pascual, Belen Masdeu, Joseph C. Hollenbeck, Mark Makris, Nikos Insausti, Ricardo Ding, Song-Lin Dickerson, Bradford C. TI Large-Scale Brain Networks of the Human Left Temporal Pole: A Functional Connectivity MRI Study SO CEREBRAL CORTEX LA English DT Article DE anterior temporal lobe; brain anatomy; cytoarchitecture; language; resting-state fMRI ID KLUVER-BUCY-SYNDROME; MEDIAL PREFRONTAL NETWORKS; COMPARATIVE CYTOARCHITECTONIC ANALYSIS; MONKEY MACACA-FASCICULARIS; DISTORTION-CORRECTED FMRI; MULTIPLE SYSTEM ATROPHY; HUMAN CEREBRAL-CORTEX; OLD-WORLD MONKEY; RHESUS-MONKEY; SEMANTIC MEMORY AB The most rostral portion of the human temporal cortex, the temporal pole (TP), has been described as "enigmatic" because its functional neuroanatomy remains unclear. Comparative anatomy studies are only partially helpful, because the human TP is larger and cytoarchitectonically more complex than in nonhuman primates. Considered by Brodmann as a single area (BA 38), the human TP has been recently parceled into an array of cytoarchitectonic subfields. In order to clarify the functional connectivity of subregions of the TP, we undertook a study of 172 healthy adults using resting-state functional connectivity MRI. Remarkably, a hierarchical cluster analysis performed to group the seeds into distinct subsystems according to their large-scale functional connectivity grouped 87.5% of the seeds according to the recently described cytoarchitectonic subregions of the TP. Based on large-scale functional connectivity, there appear to be 4 major subregions of the TP: 1) dorsal, with predominant connectivity to auditory/somatosensory and language networks; 2) ventromedial, predominantly connected to visual networks; 3) medial, connected to paralimbic structures; and 4) anterolateral, connected to the default-semantic network. The functional connectivity of the human TP, far more complex than its known anatomic connectivity in monkey, is concordant with its hypothesized role as a cortical convergence zone. C1 [Pascual, Belen; Hollenbeck, Mark; Dickerson, Bradford C.] Massachusetts Gen Hosp, MGH Frontotemporal Dementia Unit, Alzheimers Dis Res Ctr, Dept Neurol,Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Pascual, Belen; Hollenbeck, Mark; Makris, Nikos; Dickerson, Bradford C.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Masdeu, Joseph C.] NIH, Sect Integrat Neuroimaging, Bethesda, MD 20892 USA. [Makris, Nikos] Massachusetts Gen Hosp, Ctr Morphometr Anal, Dept Psychiat, Charlestown, MA 02129 USA. [Makris, Nikos] Massachusetts Gen Hosp, Ctr Morphometr Anal, Dept Neurol, Charlestown, MA 02129 USA. [Makris, Nikos] Massachusetts Gen Hosp, Ctr Morphometr Anal, Dept Radiol Serv, Charlestown, MA 02129 USA. [Makris, Nikos; Dickerson, Bradford C.] Massachusetts Gen Hosp, Ctr Neural Syst Invest, Dept Neurol, Charlestown, MA 02129 USA. [Makris, Nikos; Dickerson, Bradford C.] Massachusetts Gen Hosp, Ctr Neural Syst Invest, Dept Psychiat, Charlestown, MA 02129 USA. [Insausti, Ricardo] Univ Castilla La Mancha, Ctr Human Neuroanat Lab, Dept Hlth Sci, Sch Med, Albacete 02071, Spain. [Ding, Song-Lin] Allen Inst Brain Sci, Seattle, WA 98103 USA. RP Dickerson, BC (reprint author), MGH Frontotemporal Dementia Unit, 149 13th St,Suite 2691, Charlestown, MA 02129 USA. EM bradd@nmr.mgh.harvard.edu FU National Institute on Aging [P50-AG005134]; National Institute of Neurological Disorders and Stroke [R21-NS077059] FX Supported by grants from the National Institute on Aging (P50-AG005134) and National Institute of Neurological Disorders and Stroke (R21-NS077059). NR 151 TC 34 Z9 35 U1 8 U2 34 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD MAR PY 2015 VL 25 IS 3 BP 680 EP 702 DI 10.1093/cercor/bht260 PG 23 WC Neurosciences SC Neurosciences & Neurology GA CE6GW UT WOS:000351935800010 PM 24068551 ER PT J AU Deutsch, MB Mendez, MF AF Deutsch, Mariel B. Mendez, Mario F. TI Neurocognitive Features Distinguishing Primary Central Nervous System Lymphoma from Other Possible Causes of Rapidly Progressive Dementia SO COGNITIVE AND BEHAVIORAL NEUROLOGY LA English DT Review DE dementia; lymphoma; neurologic manifestations; neuropsychiatry ID PRIMARY CNS LYMPHOMA; CEREBRI; LEUKOENCEPHALOPATHY; MANIFESTATIONS; DIAGNOSIS; SURVIVAL AB Objective: Define the neurocognitive features of primary central nervous system lymphoma (PCNSL) presenting with dementia, and compare with other causes of rapidly progressive dementia (RPD). Background: PCNSL can present as an RPD. Differentiating PCNSL from other RPDs is critical because lymphomatous dementia may be reversible, and untreated PCNSL is fatal. Methods: We performed a meta-analysis of case reports of dementia from PCNSL (between 1950 and 2013); 20 patients (14 with lymphomatosis cerebri) met our criteria. We compared these patients to a case series of patients with RPD from Creutzfeldt-Jakob disease and other non-PCNSL etiologies (Sala et al, 2012. Alzheimer Dis Assoc Disord. 26:267-271). Results: Median age was 66 years (range 41 to 81); 70% were men. Time from symptom onset to evaluation was <6 months in 65%. No patients had seizures; 5% had headaches; 45% had non-aphasic speech difficulty. There was significantly more memory impairment in patients with PCNSL than other RPDs and significantly less myoclonus and parkinsonism. Behavioral changes and cerebellar signs were not significantly different. Significantly more patients with PCNSL than other RPDs had white matter changes; significantly fewer had atrophy. Elevated CSF protein and pleocytosis were more frequent in PCNSL; patients with other RPDs tended to have normal CSF +/- 14-3-3 protein. Conclusions: Unlike patients with RPD from other causes, those with PCNSL commonly present with impaired memory, apathy, and abnormal speech and gait, without headache, seizure, or myoclonus. White matter changes and CSF abnormalities pre-dominate. Improved clinical awareness of PCNSL can prompt earlier diagnosis and treatment. C1 [Deutsch, Mariel B.; Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Deutsch, Mariel B.; Mendez, Mario F.] Vet Affairs Greater Los Angeles Healthcare Syst, Neurobehav Unit, Los Angeles, CA 90073 USA. RP Deutsch, MB (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Neurobehav Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM marielbrooke@ucla.edu OI Deutsch, Mariel/0000-0003-1228-8868 FU National Institute on Aging [5R01AG034499] FX Supported in part by National Institute on Aging Grant 5R01AG034499 (M.F.M.). NR 30 TC 2 Z9 3 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1543-3633 EI 1543-3641 J9 COGN BEHAV NEUROL JI Cogn. Behav. Neurol. PD MAR PY 2015 VL 28 IS 1 BP 1 EP 10 PG 10 WC Behavioral Sciences; Clinical Neurology SC Behavioral Sciences; Neurosciences & Neurology GA CE5NI UT WOS:000351882000001 PM 25812125 ER PT J AU Ahnen, DJ Bresalier, RS Levin, B Kaunitz, JD AF Ahnen, Dennis J. Bresalier, Robert S. Levin, Bernard Kaunitz, Jonathan D. TI CRC Screening, Past, Present, and Future: A Tribute to Emmet Keeffe SO DIGESTIVE DISEASES AND SCIENCES LA English DT Editorial Material C1 [Ahnen, Dennis J.] Univ Colorado, Sch Med, Denver, CO 80204 USA. [Ahnen, Dennis J.] Gastroenterol Rockies, Boulder, CO USA. [Bresalier, Robert S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Levin, Bernard] New York City Colon Canc Control Coalit, New York, NY USA. [Kaunitz, Jonathan D.] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Kaunitz, Jonathan D.] UCLA Sch Med, Los Angeles, CA USA. RP Ahnen, DJ (reprint author), Univ Colorado, Sch Med, Denver, CO 80204 USA. EM dennis.ahnen@ucdenver.edu FU NCI NIH HHS [R01 CA068099] NR 5 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAR PY 2015 VL 60 IS 3 SI SI BP 589 EP 591 DI 10.1007/s10620-015-3603-2 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CE5GC UT WOS:000351858100001 PM 25724168 ER PT J AU Chacko, L Macaron, C Burke, CA AF Chacko, Lyssa Macaron, Carole Burke, Carol A. TI Colorectal Cancer Screening and Prevention in Women SO DIGESTIVE DISEASES AND SCIENCES LA English DT Review DE Colorectal cancer; Colorectal cancer prevention; Colorectal cancer screening; Colorectal cancer and women ID BODY-MASS INDEX; RANDOMIZED CONTROLLED-TRIAL; SESSILE SERRATED ADENOMAS; ESTROGEN PLUS PROGESTIN; HIGH-FIBER DIET; COLON-CANCER; CIGARETTE-SMOKING; NEGATIVE COLONOSCOPY; DIABETES-MELLITUS; FOLLOW-UP AB Colorectal cancer (CRC) is one of the leading cancers and cause of cancer deaths in American women and men. Females and males share a similar lifetime cumulative risk of CRC however, substantial differences in risk factors, tumor biology, and effectiveness of cancer prevention services have been observed between them. This review distills the evidence documenting the unique variation observed between the genders relating to CRC risk factors, screening and prevention. Consistent evidence throughout the world demonstrates that women reach equivalent levels of adenomas and CRC as men but it occurs nearly a decade later in life than in their male counterparts. Women have a higher proportion of tumors which are hypermethylated, have microsatellite instability and located in the proximal colon suggesting the serrated pathway may be of greater consequence in them than in men. Other CRC risk factors such as smoking, diet and obesity have been shown to have disparate effects on women which may related to interactions between estrogen exposure, body fat distribution, and the biologic underpinnings of their tumors. There is data showing the uptake, choice, and efficacy of different CRC screening methods in women is dissimilar to that in men. The mortality benefit from FOBT, sigmoidoscopy, and protection from interval CRC by colonoscopy appears to be lower in women than men. A greater understanding of these gender idiosyncrasies will facilitate an personalized approach to CRC prevention and should ultimately lead to a reduced burden of disease. C1 [Chacko, Lyssa] Denver Vet Affairs Med Ctr, Dept Gastroenterol & Hepatol, Denver, CO USA. [Macaron, Carole; Burke, Carol A.] Cleveland Clin, Dept Gastroenterol & Hepatol, Cleveland, OH 44195 USA. RP Burke, CA (reprint author), Cleveland Clin, Dept Gastroenterol & Hepatol, Desk A 30,9500 Euclid Ave, Cleveland, OH 44195 USA. EM Burkec1@ccf.org NR 148 TC 3 Z9 3 U1 2 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAR PY 2015 VL 60 IS 3 SI SI BP 698 EP 710 DI 10.1007/s10620-014-3452-4 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CE5GC UT WOS:000351858100015 PM 25596719 ER PT J AU Inra, JA Syngal, S AF Inra, Jennifer A. Syngal, Sapna TI Colorectal Cancer in Young Adults SO DIGESTIVE DISEASES AND SCIENCES LA English DT Review DE Colorectal cancer; Young adults; Colorectal cancer screening; Review ID SOCIETY-TASK-FORCE; II COLON-CANCER; STAGE-II; UNITED-STATES; MICROSATELLITE INSTABILITY; FERTILITY PRESERVATION; ADJUVANT CHEMOTHERAPY; CHILDHOOD-CANCER; MYH MUTATIONS; RISK AB The incidence and mortality rates of colorectal cancer (CRC) have been decreasing in adults over 50 years of age, however, these rates have been increasing in adults under 50. The majority of CRC in young adults is sporadic, and is likely due to behavioral and environmental causes, however the exact etiology still remains unclear. The minority of CRC in this population is due to inherited CRC syndromes. Young adults with CRC are often symptomatic (abdominal pain, rectal bleeding), and diagnosis is often delayed due to reasons such as under-utilized health care services, and physicians attributing symptoms to diagnoses other than CRC. Young adults with CRC often have more aggressive tumor characteristics, but they tend to have better survival rates when compared with older adults when matched for stage. Treatment is the same for young patients with CRC, however there are issues that arise in this population that do not necessarily affect older adults, such as the negative effect of chemotherapy/radiation on fertility. It is not clear that screening individuals for CRC at ages under 50 is beneficial or cost-effective. Further studies are needed regarding this topic. C1 [Inra, Jennifer A.; Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Inra, Jennifer A.; Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA 02163 USA. [Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. RP Syngal, S (reprint author), Harvard Univ, Sch Med, Boston, MA 02163 USA. EM jinra@partners.org; sapna_syngal@dfci.harvard.edu FU NCI [K24 113433] FX The authors would like to thank Matthew Yurgelun, M. D. for thoughtful review and suggestions. Supported by NCI Grant K24 113433. NR 59 TC 13 Z9 15 U1 3 U2 11 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAR PY 2015 VL 60 IS 3 SI SI BP 722 EP 733 DI 10.1007/s10620-014-3464-0 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CE5GC UT WOS:000351858100017 PM 25480403 ER PT J AU Rodriguez-Diaz, E Huang, Q Cerda, SR O'Brien, MJ Bigio, IJ Singh, SK AF Rodriguez-Diaz, Eladio Huang, Qin Cerda, Sandra R. O'Brien, Michael J. Bigio, Irving J. Singh, Satish K. TI Endoscopic histological assessment of colonic polyps by using elastic scattering spectroscopy SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID CONFOCAL LASER ENDOMICROSCOPY; DIFFUSE-REFLECTANCE SPECTROSCOPY; DIMINUTIVE COLORECTAL POLYPS; WHITE-LIGHT; IN-VIVO; VIRTUAL CHROMOENDOSCOPY; OPTICAL MAGNIFICATION; DIAGNOSTIC-ACCURACY; BARRETTS-ESOPHAGUS; COMMUNITY PRACTICE AB Background: Elastic-scattering spectroscopy (ESS) can assess in vivo and in real-time the scattering and absorption properties of tissue related to underlying pathologies. Objectives: To evaluate the potential of ESS for differentiating neoplastic from non-neoplastic polyps during colonoscopy. Design: Pilot study, retrospective data analysis. Setting: Academic practice. Patients: A total of 83 patients undergoing screening/surveillance colonoscopy. Interventions: ESS spectra of 218 polyps (133 non-neoplastic, 85 neoplastic) were acquired during colonoscopy. Spectral data were correlated with the classification of biopsy samples by 3 GI pathologists. High-dimensional methods were used to design diagnostic algorithms. Main Outcome Measurements: Diagnostic performance of ESS. Results: Analysis of spectra from polyps of all sizes (N = 218) resulted in a sensitivity of 91.5%, specificity of 92.2%, and accuracy of 91.9% with a high-confidence rate of 90.4%. Restricting analysis to polyps smaller than 1 cm (n = 179) resulted in a sensitivity of 87.0%, specificity of 92.1%, and accuracy of 90.6% with a highconfidence rate of 89.3%. Analysis of polyps 5 mm or smaller (n = 157) resulted in a sensitivity of 86.8%, specificity of 91.2%, and accuracy of 90.1% with a high-confidence rate of 89.8%. Limitations: Sample size, retrospective validation used to obtain performance estimates. Conclusion: Results indicate that ESS permits accurate, real-time classification of polyps as neoplastic or nonneoplastic. ESS is a simple, low cost, clinically robust method with minimal impact on procedure flow, especially when integrated into standard endoscopic biopsy tools. Performance on polyps 5 mm or smaller indicates that ESS may, in theory, achieve Preservation and Incorporation of Valuable Endoscopic Innovations performance thresholds. ESS may one day prove to be a useful tool used in endoscopic screening and surveillance of colorectal cancer. C1 [Rodriguez-Diaz, Eladio; Bigio, Irving J.; Singh, Satish K.] Boston Univ, Sch Med, Gastroenterol Sect, Dept Med, Boston, MA 02118 USA. [Cerda, Sandra R.; O'Brien, Michael J.] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. [Huang, Qin] Boston Univ, Coll Engn, Dept Pathol, Boston, MA 02118 USA. [Singh, Satish K.] Boston Univ, Coll Engn, Med Serv, Gastroenterol Unit, Boston, MA 02118 USA. [Rodriguez-Diaz, Eladio; Bigio, Irving J.; Singh, Satish K.] Boston Univ, Coll Engn, Dept Biomed Engn, VA Boston Healthcare Syst, Boston, MA 02118 USA. RP Singh, SK (reprint author), Boston Univ, Sch Med, Gastroenterol Sect, Dept Med, Suite 504,650 Albany St, Boston, MA 02118 USA. EM singhsk@bu.edu FU VA CSRD MERIT Award [1I01CX000347]; NIH/NCI [U54 CA10467]; Wallace H. Coulter Foundation; Center for the Integration of Medicine & Innovative Technology (CIMIT) FX The following author disclosed financial relationships relevant to this article: Dr Singh is a consultant for Mauna Kea Technologies and NinePoint Medical. All other authors disclosed no financial relationships relevant to this article. This work was supported in part by VA CSR&D MERIT Award 1I01CX000347 (S.K.S.), NIH/NCI grant U54 CA10467 (I.J.B., S.K.S.), and the Wallace H. Coulter Foundation (S.K.S., I.J.B.) and the Center for the Integration of Medicine & Innovative Technology (CIMIT) (S.K.S.). NR 49 TC 1 Z9 1 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAR PY 2015 VL 81 IS 3 BP 539 EP 547 DI 10.1016/j.gie.2014.07.012 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CE2SI UT WOS:000351666800006 PM 25257128 ER PT J AU Cadoni, S Sanna, S Gallittu, P Argiolas, M Fanari, V Porcedda, ML Erriu, M Leung, FW AF Cadoni, Sergio Sanna, Stefano Gallittu, Paolo Argiolas, Mariangela Fanari, Viviana Porcedda, Maria L. Erriu, Matteo Leung, Felix W. TI A randomized, controlled trial comparing real-time insertion pain during colonoscopy confirmed water exchange to be superior to water immersion in enhancing patient comfort SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID CARBON-DIOXIDE INSUFFLATION; UNSEDATED COLONOSCOPY; AIR INSUFFLATION; AIDED COLONOSCOPY; MINIMAL SEDATION; US VETERANS; INFUSION; MEMORIES AB Background: A recent American Society for Gastrointestinal Endoscopy Technology Status Evaluation Report recommended comparative studies of water-aided colonoscopy methods to refine the optimal insertion technique. Objective: Air insufflation (AI), water immersion (WI), and water exchange (WE) were compared head-to-head to test the hypothesis that WE produces the least insertion pain. Design: Patient-blinded, prospective, randomized, controlled trials. Setting: Two community hospitals in Italy. Patients: First-time diagnostic or screening colonoscopy in unsedated patients with the option of on-demand sedation. Intervention: Colonoscopy with AI, WI, or WE. Main Outcome Measurements: Real-time maximum insertion pain (0 = none, 10 = worst). To avoid interventional bias, the timing of recording was at the discretion of the nurse assistant. Adjunct measures were implemented to ensure patient perception of minimal discomfort. Recalled pain and patients' guess of insertion methods were recorded after colonoscopy. Results: Results were merged for 576 randomized patients. Correct patient guesses lower than 33% confirmed adequate blinding. Significant correlation (Pearson coefficient 0.6, P < .0005) between real-time and recalled pain provided internal validation of the former as the primary outcome. Real-time pain (95% confidence interval [CI]: AI, 4.1 [3.7-4.5]; WI, 3.5 [3.0-3.9]; and WE, 2.5 [2.2-2.9] [P < .0005] was the lowest in the WE group. The proportions of patients completing unsedated colonoscopy based on the assigned methods were significantly different (WE, 74.7% vs WI, 62.4%; P = .009; vs AI, 65.3%; P = .04). WE required the least implementation of adjunct maneuvers. Limitations: Unblinded colonoscopists. Conclusion: The current findings with an internally validated primary outcome in adequately blinded patients support the hypothesis that WE is superior to WI in attenuating real-time insertion pain and enhancing completion of unsedated colonoscopy. C1 [Cadoni, Sergio; Gallittu, Paolo] S Barbara Hosp, Digest Endoscopy Unit, I-09016 Iglesias, CI, Italy. [Sanna, Stefano; Argiolas, Mariangela; Fanari, Viviana; Porcedda, Maria L.] NS di Bonaria Hosp, Digest Endoscopy Unit, San Gavino Monreale, Italy. [Erriu, Matteo] Univ Cagliari, Dept Surg Sci, Cagliari, Italy. [Leung, Felix W.] Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, North Hills, CA USA. [Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Cadoni, S (reprint author), S Barbara Hosp, Digest Endoscopy Unit, Via S Leonardo 1, I-09016 Iglesias, CI, Italy. NR 27 TC 16 Z9 16 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAR PY 2015 VL 81 IS 3 BP 557 EP 566 DI 10.1016/j.gie.2014.07.029 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CE2SI UT WOS:000351666800009 PM 25262100 ER PT J AU Cuthbertson, DW Raol, N Hicks, J Green, L Parke, R AF Cuthbertson, David W. Raol, Nikhila Hicks, John Green, Linda Parke, Robert TI Minor Salivary Gland Basal Cell Adenocarcinoma A Systematic Review and Report of a New Case SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Review ID OF-THE-LITERATURE; SINGLE INSTITUTION EXPERIENCE; PAROTID-GLAND; TUMORS; PALATE; POPULATION; CARCINOMAS; CANCER; INDIA; HEAD AB IMPORTANCE Basal cell adenocarcinoma (BCAC) of the minor salivary gland is an extremely rare disease: the most recent substantive literature review reports only 25 cases. Owing to the rarity of this disease, it has not yet been well characterized in the literature. OBJECTIVE We sought to expand the knowledge of minor salivary gland BCAC by performing an exhaustive literature review and adding to it a new case that is rare owing to the tumor's size, aggressive nature, and mixed histologic pattern. The review emphasizes epidemiologic patterns, diagnostic characteristics, treatment patterns, and expected prognosis for minor salivary gland BCAC. EVIDENCE ACQUISITION In June 2012, PubMed was queried using the term "salivary gland basal cell adenocarcinoma," and the resultant articles were reviewed. Those specifically mentioning a minor salivary gland BCAC were included in this study. Those that did not differentiate minor salivary gland BCAC from major salivary gland BCAC were excluded. The search was not limited by language and included articles from North America, Europe, Africa, and Asia from 1978 to June 2012. RESULTS The PubMed search resulted in 195 articles, of which 33 articles reported at least 1 case of minor salivary gland BCAC. We report herein 72 cases of minor salivary gland BCAC (71 cases from the literature review and 1 new case reported herein). The mean patient age at the time of presentation was 56 years (range, 24-90 years), and the disease showed no sex predilection. The most common location was the palate, and the average lesions size was 2.4 cm (range, 0.7-4.2 cm). The treatment modality of choice was wide local excision (n = 57; 79%). There was a high local recurrence rate (n = 30; 41%) but a low rate of distant metastasis (n = 8; 11%). CONCLUSIONS AND RELEVANCE We present a comprehensive review of minor salivary gland BCAC, describing nearly 3 times as many cases as has been previously reported. This review characterizes a rare disease and increases awareness of the disease among otolaryngologists. Minor salivary gland BCAC is similar to major salivary gland BCAC and minor salivary gland tumors in general with regard to patient age, sex, tumor site, treatment modality, recurrence, metastasis, and mortality. C1 [Cuthbertson, David W.; Raol, Nikhila; Parke, Robert] Baylor Coll Med, Bobby R Alford Dept Otolaryngol Head & Neck Surg, Houston, TX 77030 USA. [Hicks, John; Green, Linda] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Green, Linda; Parke, Robert] Michael E Debakey Dept Vet Affairs Med Ctr, Houston, TX USA. RP Cuthbertson, DW (reprint author), Baylor Coll Med, Bobby R Alford Dept Otolaryngol Head & Neck Surg, One Baylor Plaza, Houston, TX 77030 USA. EM dwcuthbe@bcm.edu NR 45 TC 0 Z9 0 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6181 EI 2168-619X J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD MAR PY 2015 VL 141 IS 3 BP 276 EP 283 DI 10.1001/jamaoto.2014.3344 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CE1PV UT WOS:000351585000014 PM 25555241 ER PT J AU Nicksa, GA Anderson, C Fidler, R Stewart, L AF Nicksa, Grace A. Anderson, Cristan Fidler, Richard Stewart, Lygia TI Innovative Approach Using Interprofessional Simulation to Educate Surgical Residents in Technical and Nontechnical Skills in High-Risk Clinical Scenarios SO JAMA SURGERY LA English DT Article ID GRADUATE MEDICAL-EDUCATION; ACCREDITATION COUNCIL; PROGRAM DIRECTORS; AMERICAN-COLLEGE; SURGERY; IMPLEMENTATION; CHALLENGES; BEHAVIOR; IMPACT AB IMPORTANCE The Accreditation Council for Graduate Medical Education core competencies stress nontechnical skills that can be difficult to evaluate and teach to surgical residents. During emergencies, surgeons work in interprofessional teams and are required to perform certain procedures. To obtain proficiency in these skills, residents must be trained. OBJECTIVE To educate surgical residents in leadership, teamwork, effective communication, and infrequently performed emergency surgical procedures with the use of interprofessional simulations. DESIGN, SETTING, AND PARTICIPANTS SimMan 3GS was used to simulate high-risk clinical scenarios (15-20 minutes), followed by debriefings with real-time feedback (30 minutes). A modified Oxford Non-Technical Skills scale (score range, 1-4) was used to assess surgical resident performance during the first half of the academic year (July-December 2012) and the second half of the academic year (January-June 2013). Anonymous online surveys were used to solicit participant feedback. Simulations were conducted in the operating room, intensive care unit, emergency department, ward, and simulation center. A total of 43 surgical residents (postgraduate years [PGYs] 1 and 2) participated in interdisciplinary clinical scenarios, with other health care professionals (nursing, anesthesia, critical care, medicine, respiratory therapy, and pharmacy; mean number of nonsurgical participants/session: 4, range 0-9). Thirty seven surgical residents responded to the survey. EXPOSURES Simulation of high-risk clinical scenarios: postoperative pulmonary embolus, pneumothorax, myocardial infarction, gastrointestinal bleeding, anaphylaxis with a difficult airway, and pulseless electrical activity arrest. MAIN OUTCOMES AND MEASURES Evaluation of resident skills: communication, leadership, teamwork, problem solving, situation awareness, and confidence in performing emergency procedures (eg, cricothyroidotomy). RESULTS A total of 31 of 35 (89%) of the residents responding found the sessions useful. Additionally, 28 of 33 (85%) reported improved confidence doing procedures and 29 of 37 (78%) reported knowing when the procedure should be applied. Oxford Non-Technical Skills evaluation demonstrated significant improvement in PGY 2 resident performance assessed during the 2 study periods: communication score increased from 3 to 3.71 (P = .01), leadership score increased from 2.77 to 3.86 (P < .001), teamwork score increased from 3.15 to 3.86 (P = .007), and procedural ability score increased from 2.23 to 3.43 (P = .03). There were no statistically significant improved scores in PGY 2 decision making or situation awareness. No improvements in skills were seen among PGY 1 participants. CONCLUSIONS AND RELEVANCE The PGY 2 residents improved their skills, but the PGY 1 residents did not. Participants found interprofessional simulations to be realistic and a valuable educational tool. Interprofessional simulation provides a valuable means of educating surgical residents and evaluating their skills in real-life clinical scenarios. C1 [Nicksa, Grace A.; Anderson, Cristan; Fidler, Richard; Stewart, Lygia] San Francisco VA Med Ctr, Dept Surg, San Francisco, CA 94121 USA. [Nicksa, Grace A.; Anderson, Cristan; Stewart, Lygia] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94121 USA. RP Stewart, L (reprint author), San Francisco VA Med Ctr, Dept Surg, 4150 Clement St, San Francisco, CA 94121 USA. EM lygia.stewart@va.gov NR 24 TC 10 Z9 12 U1 1 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD MAR PY 2015 VL 150 IS 3 BP 201 EP 207 DI 10.1001/jamasurg.2014.2235 PG 7 WC Surgery SC Surgery GA CE2HQ UT WOS:000351636800003 PM 25565037 ER PT J AU Shunk, KA Zimmet, J Cason, B Speiser, B Tseng, EE AF Shunk, Kendrick A. Zimmet, Jeffrey Cason, Brian Speiser, Bernadette Tseng, Elaine E. TI Development of a Veterans Affairs Hybrid Operating Room for Transcatheter Aortic Valve Replacement in the Cardiac Catheterization Laboratory SO JAMA SURGERY LA English DT Article ID HIGH-RISK PATIENTS; IMPLANTATION; SURGERY; OUTCOMES; STENOSIS; MANAGEMENT; FACILITY; REGISTRY; PROGRAM AB IMPORTANCE Transcatheter aortic valve replacement (TAVR) revolutionized the treatment of aortic stenosis. Developing a TAVR program with a custom-built hybrid operating room (HOR) outside the surgical operating room area poses unique challenges in Veterans Affairs (VA) institutions. OBJECTIVE To present the process by which the San Francisco VA Medical Center developed a VA-approved TAVR program, in which an HOR exists in a cardiac catheterization laboratory, as a guideline for future programs. DESIGN, SETTING, AND PARTICIPANTS Retrospective review of each required approval process for developing an HOR in a cardiac catheterization laboratory in a VA designated for complex surgery. Participants included San Francisco VA Medical Center health care professionals and individuals responsible for new program initiation in VA institutions. EXPOSURES External reviews by industry vendors, the VA Central Office, and the Office for Construction, Facilities, and Management and an internal Healthcare Failure Mode and Effect Analysis. MAIN OUTCOMES AND MEASURES The timeline for each process. RESULTS Developing a TAVR program required vetting and approval from industry vendors, who provided training and expertise. Architectural plans for construction of the HOR began in 2010-2011, followed by approval from Edwards Lifesciences, Inc, in 2012 and fundamentals training on February 8 and 9, 2013. Following a pilot launch of the first VA TAVR program at the Houston VA Medical Center, subsequent programs were required to submit a plan to the VA Central Office for proposed restructuring of their clinical programs. After the San Francisco VA Medical Center proposal submission on February 3, 2013, a site visit consisting of a National Chief of Catheterization Laboratory Managers, a cardiac surgeon, and an interventional cardiologist with TAVR experience was conducted on April 12, 2013. During construction, HOR plans were inspected by the Office for Construction, Facilities, and Management followed by on-site inspection on August 8, 2013, to assess the adequacy of the HOR, newly built restricted corridors, equipment storage areas, and altered staff and patient flow patterns. Last, a Healthcare Failure Mode and Effect Analysis was performed to mitigate any negative effects of the HOR not being colocated in the surgical operating room area. Approval was then granted on November 13, 2013. Our first 10 TAVR cases were successfully completed as of April 2, 2014. CONCLUSIONS AND RELEVANCE The primary factor for development of a successful TAVR program is integration of the heart valve team. Particular adaptations to the cardiac catheterization laboratory environment are required to accommodate an uncompromised HOR in which cardiac and vascular surgeons can be as comfortable as their interventional cardiology colleagues. C1 [Shunk, Kendrick A.; Zimmet, Jeffrey] San Francisco VA Med Ctr, Div Cardiol, San Francisco, CA 94121 USA. [Cason, Brian] San Francisco VA Med Ctr, Dept Anesthesia, San Francisco, CA USA. [Speiser, Bernadette] Jesse Brown VA Med Ctr, Div Cardiol, Chicago, IL USA. [Tseng, Elaine E.] San Francisco VA Med Ctr, Div Cardiothorac Surg, San Francisco, CA USA. RP Tseng, EE (reprint author), UCSF Med Ctr, Div Cardiothorac Surg, 4150 Clement St,112D, San Francisco, CA 94121 USA. EM elaine.tseng@va.gov NR 22 TC 0 Z9 0 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD MAR PY 2015 VL 150 IS 3 BP 216 EP 222 DI 10.1001/jamasurg.2014.1404 PG 7 WC Surgery SC Surgery GA CE2HQ UT WOS:000351636800007 PM 25588001 ER PT J AU Boudreaux-Kelly, M Wilson, M Bokhari, M AF Boudreaux-Kelly, Monique Wilson, Mark Bokhari, Malak TI Statistical Methods of Risk-Adjusted Statistical Process Control Charts to Assess Surgical Performance in Consecutive Colorectal Operations at a Single Institution SO JAMA SURGERY LA English DT Letter C1 [Boudreaux-Kelly, Monique] Res StatCore, Pittsburgh Res Off, Pittsburgh, PA USA. [Wilson, Mark; Bokhari, Malak] VA Pittsburgh Healthcare Syst, Dept Surg, Pittsburgh, PA 15240 USA. RP Bokhari, M (reprint author), VA Pittsburgh Healthcare Syst, Dept Surg, Univ Dr Campus 112 U, Pittsburgh, PA 15240 USA. EM malak.bokhari@va.gov NR 3 TC 0 Z9 0 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD MAR PY 2015 VL 150 IS 3 BP 271 EP 272 DI 10.1001/jamasurg.2014.1773 PG 2 WC Surgery SC Surgery GA CE2HQ UT WOS:000351636800016 PM 25606809 ER PT J AU Shapiro, M Rashid, NU Huang, Q Galper, SL Boosalis, VA Whang, EE Gold, JS AF Shapiro, Mia Rashid, Naim U. Huang, Qin Galper, Shira L. Boosalis, Valia A. Whang, Edward E. Gold, Jason S. TI Radiation Therapy for Unresectable Pancreatic Adenocarcinoma: Population-Based Trends in Utilization and Survival Rates in the United States SO JAMA SURGERY LA English DT Letter ID GEMCITABINE; CANCER; TRIAL C1 [Shapiro, Mia; Whang, Edward E.; Gold, Jason S.] VA Boston Healthcare Syst, Surg Serv, West Roxbury, MA USA. [Shapiro, Mia; Rashid, Naim U.; Huang, Qin; Galper, Shira L.; Whang, Edward E.; Gold, Jason S.] Harvard Univ, Sch Med, Boston, MA USA. [Rashid, Naim U.] Dana Farber Canc Ctr, Boston, MA USA. [Huang, Qin] VA Boston Healthcare Syst, Pathol Serv, West Roxbury, MA USA. [Galper, Shira L.] VA Boston Healthcare Syst, Radiat Therapy Serv, West Roxbury, MA USA. [Galper, Shira L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Boosalis, Valia A.] VA Boston Healthcare Syst, Med Serv, West Roxbury, MA USA. [Boosalis, Valia A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Whang, Edward E.; Gold, Jason S.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Gold, JS (reprint author), VA Boston Healthcare Syst 112, Surg Serv, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM jgold4@partners.org NR 4 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 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD MAR PY 2015 VL 150 IS 3 BP 274 EP 277 DI 10.1001/jamasurg.2014.1837 PG 5 WC Surgery SC Surgery GA CE2HQ UT WOS:000351636800018 PM 25629219 ER PT J AU Smith, ER Porter, KE Messina, MG Beyer, JA Defever, ME Foa, EB Rauch, SAM AF Smith, Erin R. Porter, Katherine E. Messina, Michael G. Beyer, Jonathan A. Defever, Mahrie E. Foa, Edna B. Rauch, Sheila A. M. TI Prolonged Exposure for PTSD in a Veteran group: A pilot effectiveness study SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Prolonged Exposure therapy; Group psychotherapy; PTSD; Veterans ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL THERAPY; RAPE VICTIMS; TRIAL AB Previous research has consistently demonstrated that Prolonged Exposure (PE) therapy is an effective treatment for posttraumatic stress disorder (PTSD). Traditionally, PE has been studied and delivered on an individual basis. However, the growing number of Veterans in need of PTSD treatment has led to increased interest in group therapies as an efficient way to provide access to care. The current study examined a group and individual hybrid treatment that was developed based on PE principles. Treatment was 12 weeks in length and consisted of 12 one-hour group sessions focused on in vivo exposures, and an average of approximately five-hour long individual imaginal exposure sessions. Data for this study were derived from 67 veterans who participated in 12 cohorts of the Group PE. Significant reductions in PTSD and depression symptoms were found in both completers and intent-to-treat sample analyses. The clinical implications of these findings are discussed. Published by Elsevier Ltd. C1 [Smith, Erin R.; Porter, Katherine E.; Rauch, Sheila A. M.] VA Ann Arbor Healthcare Syst, Mental Hlth Serv, Ann Arbor, MI 48105 USA. [Smith, Erin R.; Porter, Katherine E.; Rauch, Sheila A. M.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. [Messina, Michael G.] William S Middleton Mem Vet Adm Med Ctr, Mental Hlth Serv, Madison, WI USA. [Messina, Michael G.] Univ Wisconsin, Dept Psychiat, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Beyer, Jonathan A.] Jesse Brown VA Med Ctr, Mental Hlth Serv, Chicago, IL USA. [Foa, Edna B.] Univ Penn, Philadelphia, PA 19104 USA. RP Smith, ER (reprint author), VA Ann Arbor Healthcare Syst, 2215 Fuller Rd, Ann Arbor, MI 48105 USA. EM Erin.Smith3@va.gov RI Rauch, Sheila/K-4450-2015 OI Rauch, Sheila/0000-0001-9686-4011 FU CDA-2 Award from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development FX Dr. Rauch's contribution was based upon work supported by a CDA-2 Award from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development. NR 33 TC 5 Z9 5 U1 3 U2 12 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 MAR PY 2015 VL 30 BP 23 EP 27 DI 10.1016/j.janxdis.2014.12.008 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CE2PX UT WOS:000351658600005 PM 25594370 ER PT J AU Dadfar, N Seyyedi, M Forghani, R Curtin, HD AF Dadfar, Nazanin Seyyedi, Mohammad Forghani, Reza Curtin, Hugh D. TI Computed Tomography Appearance of Normal Nonossified Thyroid Cartilage Implication for Tumor Invasion Diagnosis SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE thyroid cartilage; nonossified; laryngeal cancer; CT scan ID DUAL-ENERGY CT; SQUAMOUS-CELL CARCINOMA; LARYNGEAL CARCINOMA; HYPOPHARYNGEAL CANCER; NEOPLASTIC INVASION; FRAMEWORK AB Objective: The objective of this study was to determine the density and homogeneity of the nonossified thyroid cartilage (NOTC) on contrast-enhanced computed tomography (CT) providing preliminary information for future evaluation of cartilage invasion using dual-energy CT. Methods: One hundred normal-larynx CT scans were evaluated for the density and homogeneity of NOTC. Results: The density of the NOTC was homogeneous in all cases. Nonossified thyroid cartilage had higher mean density than contiguous muscle, but there was overlap. In 47 cases, a lucent area was observed at the junction of the ossified and NOTC but not within the NOTC itself. In 11 cases, ossification was observed in only 1 cortex of the thyroid cartilage. Cartilage at the anterior commissure was not ossified in 7 cases. Conclusions: Nonossified thyroid cartilage has a homogeneous appearance on contrast-enhanced CT scans, but showed some normal variations that could be mistakenly reported as tumor invasion. C1 [Dadfar, Nazanin; Curtin, Hugh D.] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. [Seyyedi, Mohammad] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Seyyedi, Mohammad] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Forghani, Reza] McGill Univ, Jewish Gen Hosp, Dept Radiol, Montreal, PQ H3T 1E2, Canada. [Forghani, Reza] McGill Univ, Montreal, PQ, Canada. RP Curtin, HD (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St Lobby, Boston, MA 02114 USA. EM hugh_curtin@meei.harvard.edu NR 24 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0363-8715 EI 1532-3145 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAR-APR PY 2015 VL 39 IS 2 BP 240 EP 243 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CE2VC UT WOS:000351677000018 PM 25564299 ER PT J AU Loboprabhu, S Molinari, V Asghar-Ali, AA AF Loboprabhu, Sheila Molinari, Victor Asghar-Ali, Ali Abbas TI Castaways: Addressing Hostility and Helplessness in Severely Lonely Adults SO JOURNAL OF PSYCHIATRIC PRACTICE LA English DT Article DE hostility; helplessness; loneliness; validation; mentalization; reality orientation; socialization ID ATTACHMENT RELATIONSHIPS; LONELINESS; SELF; CHILDHOOD; PREDICTORS; CHILDREN; BEHAVIOR; TRAUMA; MODEL; LIFE AB Hostility and helplessness are recurrent themes in severely lonely adults, and they can be both causes and effects of subjective feelings of loneliness. Since many lonely patients report a history of abuse, hostile and helpless states of mind may reflect identification with hostile (aggressor) or helpless (passive) attachment figures. Hostile intrusiveness and helpless withdrawal by the parent are 2 distinct patterns of parent-child misattunement that can lead to infant disorganization via disrupted emotional communication and to loneliness later in life. Anxious-ambivalent lonely older adults tend to exhibit hyperactivating hostile behaviors (to deal with a core sense of powerlessness), whereas those with fearful-avoidant attachment styles exhibit deactivating helpless behaviors (to deflect intense underlying feelings of rage). Based on this model, we outline different treatment approaches for lonely persons with different attachment styles by describing the successful treatment of two severely lonely, suicidal veterans. We describe an approach to treating hostile and helpless behaviors in lonely patients, using validation, mentalization, reality orientation, and socialization. Validation provides a sense of safety and rapport. Mentalization allows the lonely individual to better appreciate his or her own mental processes and those of others. Reality orientation provides feedback to lonely individuals on whether their perceptions are accurate and reality-based and helps them appreciate the consequences their behavior may have for self and others. Finally, socialization reduces disenfranchisement by teaching/re-teaching individuals social skills that may have become impaired by prolonged isolation. C1 [Loboprabhu, Sheila; Asghar-Ali, Ali Abbas] Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. [Loboprabhu, Sheila; Asghar-Ali, Ali Abbas] Baylor Coll Med, Houston, TX 77030 USA. [Molinari, Victor] Univ S Florida, Tampa, FL USA. RP Loboprabhu, S (reprint author), Michael E DeBakey Dept Vet Affairs Med Ctr, Mental Hlth Care Line, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM SheilaM.Loboprabhu@va.gov NR 45 TC 0 Z9 0 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1527-4160 EI 1538-1145 J9 J PSYCHIATR PRACT JI J. Psychiatr. Pract. PD MAR PY 2015 VL 21 IS 2 BP 93 EP 106 DI 10.1097/01.pra.0000462602.94853.2f PG 14 WC Psychiatry SC Psychiatry GA CE2TR UT WOS:000351672100002 PM 25782760 ER PT J AU Heo, JY Jeon, HJ Fava, M Mischoulon, D Baer, L Clam, A Doorley, J Pisoni, A Papakostas, GI AF Heo, Jung-Yoon Jeon, Hong Jin Fava, Maurizio Mischoulon, David Baer, Lee Clam, 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 JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Ziprasidone; Major depressive disorder; Anxious depression; Efficacy; Monotherapy ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; STAR-ASTERISK-D; NONANXIOUS DEPRESSION; CLINICAL-TRIALS; HUMAN BRAIN; DSM-IV; DISORDER; RECEPTORS; RELEASE; BINDING AB Anxious depression, defined as major depressive disorder (MDD) accompanied by high levels of anxiety, seems to be difficult to treat with traditional antidepressant monotherapy. The purpose of this study was to assess the efficacy of ziprasidone monotherapy in patients with anxious depression versus non-anxious depression. One hundred and twenty outpatients were enrolled in a 12-week study that was divided into two 6-week periods according to the sequential parallel comparison design. Patients were randomized in a 2:3:3 multi-ratio to receive ziprasidone for 12 weeks, placebo for 6 weeks, followed by ziprasidone for 6 weeks, or placebo for 12 weeks. Efficacy was measured according to the 17-item Hamilton Depression Rating Scale (HRDS-17), Quick Inventory of Depressive Symptomatology Self-Rated (QIDS-SR). Anxious depression was defined as a score of >= 7 on the HDRS-17 anxiety/somatization subscale. In phase I and II, ziprasidone monotherapy led to no significant changes compared with placebo on the HDRS-17 and QIDS-SR scores in patients with both anxious and non-anxious depression. In the pooled analysis, ziprasidone monotherapy also produced no significance on the HDRS-17 (Z = 0.25, P = 0.80) and QIDS-SR (Z = 0.43, P = 0.67) in patients with anxious depression. In conclusion, treatment with ziprasidone monotherapy may produce no significant improvement compared with placebo in patients with in anxious depression. Trial registration: ClinicalTrials.gov identifier: NCT00555997. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Heo, Jung-Yoon; Jeon, Hong Jin] Sungkyunkwan Univ, Dept Psychiat, Depress Ctr, Samsung Med Ctr,Sch Med, Seoul 135710, South Korea. [Jeon, Hong Jin; Fava, Maurizio; Mischoulon, David; Baer, Lee; Clam, Alisabet; Doorley, James; Pisoni, Angela; Papakostas, George I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. [Jeon, Hong Jin] Sungkyunkwan Univ, Dept Clin Res Design & Evaluat, SAIHST, Seoul 135710, South Korea. [Jeon, Hong Jin] Sungkyunkwan Univ, Dept Med Device Management & Res, SAIHST, Seoul 135710, South Korea. RP Jeon, HJ (reprint author), Sungkyunkwan Univ, Dept Psychiat, Depress Ctr, Samsung Med Ctr,Sch Med, 50 Irwon Dong, Seoul 135710, South Korea. EM jeonhj@skku.edu FU Pfizer Inc.; Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2011-0013064]; Samsung Medical Center Clinical Research Development Program (CRDP) [SMO1131461] FX This trial was supported by Pfizer Inc. This research was also 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), and the Samsung Medical Center Clinical Research Development Program (CRDP) Grant SMO1131461. They had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 35 TC 1 Z9 1 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD MAR PY 2015 VL 62 BP 56 EP 61 DI 10.1016/j.jpsychires.2015.01.007 PG 6 WC Psychiatry SC Psychiatry GA CE4GS UT WOS:000351789700007 PM 25659187 ER PT J AU Zhang, CR Cloonan, L Fitzpatrick, KM Kanakis, AS Ayres, AM Furie, KL Rosand, J Rost, NS AF Zhang, Cathy R. Cloonan, Lisa Fitzpatrick, Kaitlin M. Kanakis, Allison S. Ayres, Alison M. Furie, Karen L. Rosand, Jonathan Rost, Natalia S. TI Determinants of White Matter Hyperintensity Burden Differ at the Extremes of Ages of Ischemic Stroke Onset SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Leukoaraiosis; white matter disease; risk factor; acute cerebral infarction; CT and MRI; risk factors for stroke ID SMALL VESSEL DISEASE; LACUNAR STROKE; RISK-FACTORS; LEUKOARAIOSIS; VOLUME; SUSCEPTIBILITY; PROGRESSION; HEMORRHAGE; SEVERITY; OLD AB Background: Age is a well-known risk factor for both stroke and increased burden of white matter hyperintensity (WMH), as detected on magnetic resonance imaging (MRI) scans. However, in patients diagnosed with ischemic stroke (IS), WMH volume (WMHv) varies significantly across age groups. We sought to examine the determinants of WMH burden across the ages of stroke onset with the goal to uncover potential age-specific stroke prevention targets. Methods: Adult subjects from an ongoing hospital-based cohort study of IS patients with admission brain MRI were categorized as having early (< 55 years), late (> 75 years), or average (55-75 years) age of stroke onset. WMHv was measured using a previously validated, MRI-based semi-automated method and normalized for linear regression analyses. Results: Of 1008 IS subjects, 249 had early-onset stroke (24.7%), and 311 had late-onset stroke (30.9%). In multivariable analysis of WMHv using backward stepwise selection, only age (beta = .02, P = .018), hypertension (beta = .24, P = .049), and history of tobacco use (beta = .38, P = .001) were independently associated with WMHv in patients with early-onset stroke, whereas male sex (beta = -.30, P = .007), hyperlipidemia (beta = -.27, P = .015), and current alcohol use (beta = .23, P = .034) were independently associated with WMHv in patients with late-onset stroke. Conclusions: History of tobacco use is a strong independent predictor of WMH burden in patients with early-onset stroke, whereas age is no longer associated with WMHv in IS patients older than 75 years of age. These findings suggest that the major risk factors to target for stroke prevention differ across age groups and may be modifiable. C1 [Zhang, Cathy R.; Cloonan, Lisa; Fitzpatrick, Kaitlin M.; Kanakis, Allison S.; Ayres, Alison M.; Rosand, Jonathan; Rost, Natalia S.] Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. [Rosand, Jonathan; Rost, Natalia S.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Furie, Karen L.] Rhode Isl Hosp, Providence, RI USA. RP Rost, NS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM nrost@partners.org FU American Heart Association Bugher Foundation; Deane Institute for Integrative Research in Atrial Fibrillation and Stroke; Massachusetts General Hospital; National Institute of Neurological Disorders and Stroke (NINDS) [K23 NS064052, R01 NS082285]; NINDS [5P50NS051343-04, 5R01NS059727, 5P50NS051343, R01NS063925, K23NS064052, R01NS082285] FX This study was supported by project grants from the American Heart Association Bugher Foundation, the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, Massachusetts General Hospital, and the National Institute of Neurological Disorders and Stroke (NINDS grants K23 NS064052 and R01 NS082285). C.R.Z., L.C., K.F., A.K., and A.M.A. report no disclosures. K.L.F. is supported by the NINDS (5P50NS051343-04). J.R. is supported by the NINDS (5R01NS059727, 5P50NS051343, R01NS063925) and the American Heart Association Bugher Foundation. N.S.R. is supported by the NINDS (K23NS064052 and R01NS082285). NR 32 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 EI 1532-8511 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD MAR PY 2015 VL 24 IS 3 BP 649 EP 654 DI 10.1016/j.jstrokecerebrovasdis.2014.10.016 PG 6 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CE5FB UT WOS:000351855000027 PM 25576348 ER PT J AU Enguidanos, S Kogan, AMC Schreibeis-Baum, H Lendon, J Lorenz, K AF Enguidanos, Susan Kogan, Alexis M. Coulourides Schreibeis-Baum, Hannah Lendon, Jessica Lorenz, Karl TI "Because I Was Sick": Seriously Ill Veterans' Perspectives on Reason for 30-Day Readmissions SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE readmission; seriously ill; cancer; heart failure; palliative care ID HOSPITAL READMISSION; PALLIATIVE CARE; MEDICARE BENEFICIARIES; COST AB ObjectivesTo determine the perspectives of seriously ill individuals on reasons for 30-day hospital readmission. DesignA prospective qualitative study was conducted employing individual interviews conducted at bedside. SettingDepartment of Veterans Affairs Greater Los Angeles Healthcare System. ParticipantsSeriously ill individuals with heart failure or cancer receiving inpatient palliative care and readmitted to the hospital within 30days of hospital discharge were recruited to participate. Nine were interviewed. MeasurementsA semistructured interview protocol was used to elicit participant perspectives on readmission causes. ResultsAll participants were male and had a mean age of 70.19.5. Participants were ethnically diverse (three African Americans, three Caucasians, three Hispanic or mixed ethnic background). Six lived alone, and four did not have caregiver support. Qualitative analysis of transcripts revealed three themes relating to reasons for hospital readmission: lack of caregiver support and motivation to provide self-care, acceptance of condition and desire for aggressive care, and access to care and poor quality of care. ConclusionParticipants identified potentially avoidable reasons for hospital readmission as well as causes that require rethinking regarding how community support is targeted and delivered. Participant preference for aggressive care, inability to provide self-care, and lack of caregiver support suggest the need for new and innovative mechanisms to support seriously ill community-dwelling individuals. C1 [Enguidanos, Susan; Kogan, Alexis M. Coulourides] Univ So Calif, Leonard Davis Sch Gerontol, Los Angeles, CA 90089 USA. [Schreibeis-Baum, Hannah; Lendon, Jessica; Lorenz, Karl] US Dept Vet Affairs, Los Angeles, CA USA. RP Enguidanos, S (reprint author), Univ So Calif, Davis Sch Gerontol, 3715 McClintock Ave, Los Angeles, CA 90089 USA. EM Susan.Enguidanos@usc.edu OI Enguidanos, Susan/0000-0002-5112-288X FU National Palliative Care Research Center FX This study was supported by a career development award from the National Palliative Care Research Center. Hannah Schreibeis-Baum, Jessica Lendon, and Karl Lorenz are employed by the VA, the site of the research study. Susan Enguidanos and Alexis Coulourides Kogan received grant funds from the National Palliative Care Research Center to conduct this research. NR 26 TC 2 Z9 2 U1 1 U2 4 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 MAR PY 2015 VL 63 IS 3 BP 537 EP 542 DI 10.1111/jgs.13238 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CE3PO UT WOS:000351740400015 PM 25732270 ER PT J AU Paquin, AM Salow, M Rudolph, JL AF Paquin, Allison M. Salow, Marci Rudolph, James L. TI Pharmacist Calls to Older Adults with Cognitive Difficulties After Discharge in a Tertiary Veterans Affairs Medical Center: A Quality Improvement Program SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE transitions in care; medication safety; medication reconciliation ID HOSPITAL DISCHARGE; CARE; RECONCILIATION; DISCREPANCIES; PATIENT; IMPACT; SCALE AB ObjectivesTo evaluate the effect of the Pharmacological Intervention in Late Life (PILL) Service, which provides pharmacist telephone follow-up after discharge of older adults from the hospital, on postdischarge acute care utilization. DesignRetrospective, secondary data analysis of a quality improvement project from 2010 to 2012. SettingTertiary Veterans Affairs hospital. ParticipantsParticipants were inpatients aged 65 and older with delirium risk or prescribed a dementia medication (N=501, mean age 79.58.0; 98% male). MeasurementsPILL Service pharmacist telephone follow-up included a medication review and reconciliation within 5days after hospital discharge. The time of the pharmacist call was examined in relation to the outcomes of emergency and urgent care encounters, readmissions, and mortality within 60days. ResultsThe average number of discharge medications was 14.8 +/- 5.7 with 2.8 +/- 2.2 medication changes and 1.4 +/- 1.8 discrepancies between medication order and instruction. After adjustment for age, number of medication changes, and number of discrepancies, every additional 5minutes of pharmacist call was associated with a 15% reduction in 60-day readmission (adjusted odds ratio (OR)=0.85, 95% confidence interval (95% CI)=0.75-0.97) but was not associated with emergency or urgent care encounters (adjusted OR=1.03, 95% CI=0.91-1.17) or mortality (adjusted OR=0.84, 95% CI=0.58-1.20). ConclusionPharmacist-led medication review, reconciliation, and telephone calls after hospital discharge were associated with fewer 60-day hospital readmissions in this quality improvement program. C1 [Paquin, Allison M.; Salow, Marci] VA Boston Healthcare Syst, Dept Pharm, Boston, MA USA. [Paquin, Allison M.; Salow, Marci] Northeastern Univ, Dept Clin Pharm Practice, Boston, MA 02115 USA. [Rudolph, James L.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Rudolph, James L.] Harvard Univ, Sch Med, Boston, MA USA. RP Rudolph, JL (reprint author), VABHS GRECC, 150 S Huntington Ave, Boston, MA 02130 USA. EM jrudolph@partners.org FU VA Rehabilitation Career Development and Patient Safety Center of Inquiry grants; Veterans Engineering Resource Network; Center for Integration of Medicine and Innovative Technology; VA Central Office of Geriatrics and Extended Care Non-institutional Alternatives to Extended Care grant; American Society of Health-System Pharmacists Research and Education Foundation FX Drs. Paquin, Salow, and Rudolph are employees of the U.S. government. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. Dr. Rudolph is supported by VA Rehabilitation Career Development and Patient Safety Center of Inquiry grants. Drs. Paquin, Salow, and Rudolph have been supported by the VA grant described above. Dr. Paquin has participated in research supported by the Veterans Engineering Resource Network and the Center for Integration of Medicine and Innovative Technology. Drs. Paquin and Rudolph had full access to study data and take responsibility for the integrity and accuracy of this analysis. None of the authors has any financial and personal conflicts to report.; The project reported here was supported by the VA Central Office of Geriatrics and Extended Care Non-institutional Alternatives to Extended Care grant. The American Society of Health-System Pharmacists Research and Education Foundation supported preparation of this manuscript. NR 22 TC 2 Z9 2 U1 1 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 MAR PY 2015 VL 63 IS 3 BP 571 EP 577 DI 10.1111/jgs.13315 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CE3PO UT WOS:000351740400021 PM 25732548 ER PT J AU Kron, IL Hung, J Overbey, JR Bouchard, D Gelijns, AC Moskowitz, AJ Voisine, P O'Gara, PT Argenziano, M Michler, RE Gillinov, M Puskas, JD Gammie, JS Mack, MJ Smith, PK Sai-Sudhakar, C Gardner, TJ Ailawadi, G Zeng, X O'Sullivan, K Parides, MK Swayze, R Thourani, V Rose, EA Perrault, LP Acker, MA AF Kron, Irving L. Hung, Judy Overbey, Jessica R. Bouchard, Denis Gelijns, Annetine C. Moskowitz, Alan J. Voisine, Pierre O'Gara, Patrick T. Argenziano, Michael Michler, Robert E. Gillinov, Marc Puskas, John D. Gammie, James S. Mack, Michael J. Smith, Peter K. Sai-Sudhakar, Chittoor Gardner, Timothy J. Ailawadi, Gorav Zeng, Xin O'Sullivan, Karen Parides, Michael K. Swayze, Roger Thourani, Vinod Rose, Eric A. Perrault, Louis P. Acker, Michael A. CA CSTN Investigators TI Predicting recurrent mitral regurgitation after mitral valve repair for severe ischemic mitral regurgitation SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID PAPILLARY-MUSCLE DYSFUNCTION; DILATED CARDIOMYOPATHY; HEART-FAILURE; RESTRICTIVE ANNULOPLASTY; ECHOCARDIOGRAPHY; REPLACEMENT; RECOMMENDATIONS; MECHANISM; DISEASE; SURGERY AB Objectives: The Cardiothoracic Surgical Trials Network recently reported no difference in the primary end point of left ventricular end-systolic volume index at 1 year postsurgery in patients randomized to repair (n = 126) or replacement (n = 125) for severe ischemic mitral regurgitation. However, patients undergoing repair experienced significantly more recurrent mitral regurgitation than patients undergoing replacement (32.6% vs 2.3%). We examined whether baseline echo-cardiographic and clinical characteristics could identify those who will develop moderate/severe recurrent mitral regurgitation or die. Methods: Our analysis includes 116 patients who were randomized to and received mitral valve repair. Logistic regression was used to estimate a model-based probability of recurrence or death from baseline factors. Receiver operating characteristic curves were constructed from these estimated probabilities to determine classification cut-points maximizing accuracy of prediction based on sensitivity and specificity. Results: Of the 116 patients, 6 received a replacement before leaving the operating room; all other patients had mild or less mitral regurgitation on intraoperative echo-cardiogram after repair. During the 2-year follow-up period, 76 patients developed moderate/severe mitral regurgitation or died (53 mitral regurgitation recurrences, 13 mitral regurgitation recurrences and death, and 10 deaths). The mechanism for recurrent mitral regurgitation was largely mitral valve leaflet tethering. Our model (including age, body mass index, sex, race, effective regurgitant orifice area, basal aneurysm/dyskinesis, New York Heart Association class, history of coronary artery bypass grafting, percutaneous coronary intervention, or ventricular arrhythmias) yielded an area under the receiver operating characteristic curve of 0.82. Conclusions: The model demonstrated good discrimination in identifying patients who will survive 2 years without recurrent mitral regurgitation after mitral valve repair. Although our results require validation, they offer a clinically relevant risk score for selection of surgical candidates for this procedure. C1 [Kron, Irving L.; Ailawadi, Gorav] Univ Virginia, Sch Med, Div Thorac & Cardiovasc Surg, Charlottesville, VA 22908 USA. [Hung, Judy; Zeng, Xin] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Overbey, Jessica R.; Gelijns, Annetine C.; Moskowitz, Alan J.; O'Sullivan, Karen; Parides, Michael K.; Rose, Eric A.] Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, Int Ctr Hlth Outcomes & Innovat Res InCHOIR, New York, NY 10029 USA. [Bouchard, Denis; Perrault, Louis P.] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada. [Voisine, Pierre] Hop Laval, Inst Univ Cardiol Quebec, Montreal, PQ, Canada. [O'Gara, Patrick T.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Argenziano, Michael] Columbia Univ, Coll Phys & Surg, Dept Surg, Div Cardiothorac Surg, New York, NY USA. [Michler, Robert E.; Swayze, Roger] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Cardiothorac Surg, New York, NY USA. [Gillinov, Marc] Cleveland Clin Fdn, Dept Thorac & Cardiovasc Surg, Cleveland, OH 44195 USA. [Puskas, John D.; Thourani, Vinod] Icahn Sch Med Mt Sinai, Mt Sinai Beth Israel, Cardiothorac Surg, Dept Cardiac Surg, New York, NY 10029 USA. [Gammie, James S.] Univ Maryland, Dept Cardiac Surg, Baltimore, MD 21201 USA. [Mack, Michael J.] Baylor Scott & White Hlth, Baylor Res Inst, Cardiothorac Surg, Plano, TX USA. [Smith, Peter K.] Duke Univ, Div Cardiovasc & Thorac Surg, Durham, NC USA. [Sai-Sudhakar, Chittoor] Ohio State Univ, Med Ctr, Cardiac Surg, Columbus, OH 43210 USA. [Gardner, Timothy J.] Christiana Care Hlth Syst, Ctr Heart & Vasc Hlth, Newark, DE USA. [Acker, Michael A.] Univ Penn, Dept Surg, Div Cardiovasc Surg, Sch Med, Philadelphia, PA 19104 USA. RP Gelijns, AC (reprint author), Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, InCHOIR, New York, NY 10029 USA. EM Annetine.gelijns@mountsinai.edu OI Moskowitz, Alan/0000-0002-4412-9450; Browndyke, Jeffrey/0000-0002-8573-7073 FU National Heart, Lung, and Blood Institute, Bethesda, Md; Canadian Institutes of Health Research, Ottawa, Ontario; National Institute of Neurological Diseases and Stroke, Bethesda, Md [7U01 HL088942] FX Funded by a cooperative agreement of The National Heart, Lung, and Blood Institute, Bethesda, Md; the Canadian Institutes of Health Research, Ottawa, Ontario; and the National Institute of Neurological Diseases and Stroke, Bethesda, Md (Grant 7U01 HL088942). (ClinicalTrials.gov number NCT00807040). NR 44 TC 38 Z9 39 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAR PY 2015 VL 149 IS 3 BP 752 EP + DI 10.1016/j.jtcvs.2014.10.120 PG 11 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CE6EX UT WOS:000351930600040 PM 25500293 ER PT J AU Inaba, K Nosanov, L Menaker, J Bosarge, P Williams, L Turay, D Cachecho, R de Moya, M Bukur, M Carl, J Kobayashi, L Kaminski, S Beekley, A Gomez, M Skiada, D AF Inaba, Kenji Nosanov, Lauren Menaker, Jay Bosarge, Patrick Williams, Lashonda Turay, David Cachecho, Riad de Moya, Marc Bukur, Marko Carl, Jordan Kobayashi, Leslie Kaminski, Stephen Beekley, Alec Gomez, Mario Skiada, Dimitra CA AAST TL-Spine Multictr Study Grp TI Prospective derivation of a clinical decision rule for thoracolumbar spine evaluation after blunt trauma: An American Association for the Surgery of Trauma Multi-Institutional Trials Group Study SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article; Proceedings Paper CT 73rd Annual Meeting of the American-Association-for-the-Surgery-of-Trauma / Clinical Congress of Acute Care Surgery CY SEP 09-13, 2014 CL Philadelphia, PA SP Amer Assoc Surg Trauma DE Thoracolumbar; spine; trauma; diagnostic; evaluation ID LUMBAR SPINE; COMPUTED-TOMOGRAPHY; FRACTURES; INJURIES; RADIOGRAPHS; CRITERIA; RISK; CLASSIFICATION; CLEARANCE; ACCURACY AB BACKGROUND: Unlike the cervical spine (C-spine), where National Emergency X-Radiography Utilization Study (NEXUS) and the Canadian C-spine Rules can be used, evidence-based thoracolumbar spine (TL-spine) clearance guidelines do not exist. The aim of this study was to develop a clinical decision rule for evaluating the TL-spine after injury. METHODS: Adult (>= 15 years) blunt trauma patients were prospectively enrolled at 13 US trauma centers (January 2012 to January 2014). Exclusion criteria included the following: C-spine injury with neurologic deficit, preexisting paraplegia/tetraplegia, and unevaluable examination. Remaining evaluable patients underwent TL-spine imaging and were followed up to discharge. The primary end point was a clinically significant TL-spine injury requiring TL-spine orthoses or surgical stabilization. Regression techniques were used to develop a clinical decision rule. Decision rule performance in identifying clinically significant fractures was tested. RESULTS: Of 12,479 patients screened, 3,065 (24.6%) met inclusion criteria (mean [SD] age, 43.5 [19.8] years [range, 15-103 years]; male sex, 66.3%; mean [SD] Injury Severity Score [ISS], 8.8 [7.5]). The majority underwent computed tomography (93.3%), 6.3% only plain films, and 0.2% magnetic resonance imaging exclusively. TL-spine injury was identified in 499 patients (16.3%), of which 264 (8.6%) were clinically significant (29.2% surgery, 70.8% TL-spine orthosis). The majority was AO Type A1 282 (56.5%), followed by 67 (13.4%) A3, 43 (8.6%) B2, and 32 (6.4%) A4 injuries. The predictive ability of clinical examination (pain, midline tenderness, deformity, neurologic deficit), age, and mechanism was examined; positive clinical examination finding resulted in a sensitivity of 78.4% and a specificity of 72.9%. Addition of age of 60 years or older and high-risk mechanism (fall, crush, motor vehicle crash with ejection/rollover, unenclosed vehicle crash, auto vs. pedestrian) increased sensitivity to 98.9% with specificity of 29.0% for clinically significant injuries and 100.0% sensitivity and 27.3% specificity for injuries requiring surgery. CONCLUSION: Clinical examination alone is insufficient for determining the need for imaging in evaluable patients at risk of TL-spine injury. Addition of age and high-risk mechanism results in a clinical decision-making rule with a sensitivity of 98.9% for clinically significant injuries. (Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.) C1 [Inaba, Kenji; Nosanov, Lauren; Skiada, Dimitra] Univ So Calif, Div Trauma & Surg Crit Care, Los Angeles, CA 90033 USA. [Turay, David] Loma Linda Univ, Dept Surg, Loma Linda, CA 92350 USA. [Kobayashi, Leslie] Univ Calif San Diego, Dept Surg, Div Trauma Surg Crit Care & Burns, La Jolla, CA 92093 USA. [Kaminski, Stephen] Santa Barbara Cottage Hosp, Trauma Serv, Santa Barbara, CA USA. [Menaker, Jay] Univ Maryland, Sch Med, Dept Surg, R Adams Cowley Shock Trauma Ctr, Baltimore, MD 21201 USA. [Bosarge, Patrick] Univ Alabama Birmingham, Div Trauma Burns & Surg Crit Care, Birmingham, AL USA. [Williams, Lashonda] East Texas Med Ctr, Dept Trauma, Tyler, TX USA. [Carl, Jordan] Univ Texas Southwestern Austin, Dept Surg, Austin, TX USA. [Cachecho, Riad] Crozer Chester Med Ctr, Dept Surg, Upland, NY USA. [Beekley, Alec] Thomas Jefferson Univ, Div Acute Care Surg, Philadelphia, PA 19107 USA. [de Moya, Marc] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma, Boston, MA USA. [Bukur, Marko] Florida Int Univ, Broward Gen Med Ctr, Miami, FL 33199 USA. [Gomez, Mario] Lutheran Med Ctr, Div Trauma & Surg Crit Care, Brooklyn, NY USA. RP Inaba, K (reprint author), Univ So Calif, LAC USC Med Ctr, Div Trauma & Surg Crit Care, IPT, 2051 Marengo St,C5L 100, Los Angeles, CA 90033 USA. EM KInaba@surgery.usc.edu NR 28 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD MAR PY 2015 VL 78 IS 3 BP 459 EP 465 DI 10.1097/TA.0000000000000560 PG 7 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA CE8DQ UT WOS:000352072000003 PM 25710414 ER PT J AU Dawes, AJ Sacks, GD Cryer, HG Gruen, JP Preston, C Gorospe, D Cohen, M McArthur, DL Russell, MM Maggard-Gibbons, M Ko, CY AF Dawes, Aaron J. Sacks, Greg D. Cryer, H. Gill Gruen, J. Peter Preston, Christy Gorospe, Deidre Cohen, Marilyn McArthur, David L. Russell, Marcia M. Maggard-Gibbons, Melinda Ko, Clifford Y. CA Los Angeles Cty Trauma Consortium TI Intracranial pressure monitoring and inpatient mortality in severe traumatic brain injury: A propensity score-matched analysis SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article; Proceedings Paper CT 73rd Annual Meeting of the American-Association-for-the-Surgery-of-Trauma / Clinical Congress of Acute Care Surgery CY SEP 09-13, 2014 CL Philadelphia, PA SP Amer Assoc Surg Trauma DE Traumatic brain injury; intracranial pressure monitoring; mortality; propensity score ID SEVERE HEAD-INJURY; EVIDENCE-BASED GUIDELINES; UNITED-STATES; CARE; HOSPITALIZATION; IMPROVEMENT; MANAGEMENT; OUTCOMES; CENTERS AB BACKGROUND: Although intracranial pressure (ICP) monitoring in severe traumatic brain injury (TBI) is recommended by the Brain Trauma Foundation, the benefits remain controversial. We sought to determine the impact of ICP monitor placement on inpatient mortality within a regional trauma system after correcting for selection bias through propensity score matching. METHODS: Data were collected on all severe TBI cases presenting to 14 trauma centers during the 2-year study period (2009-2010). Inclusion criteria were as follows: blunt injury, Glasgow Coma Scale (GCS) score of 8 or lower in the emergency department, and abnormal intracranial findings on head computed tomography (CT). Two separate multivariate logistic regression models were used to predict ICP monitor placement and inpatient mortality after controlling for demographics, severity of injury, comorbidities, and TBI-specific variables (GCS score, pupil reactivity, international normalized ratio, and nine specific head CT findings). To account for selection bias, we developed a propensity score-matched model to estimate the "true'' effect of ICP monitoring on in-hospital mortality. RESULT: A total of 844 patients met inclusion criteria; 22 died on arrival to the emergency department. Inpatient mortality was 38.8%; 46.0% of the patients underwent ICP monitor placement. Unadjusted mortality rates were significantly lower in the ICP monitoring group (30.7% vs. 45.7%, p < 0.001). ICP monitor placement was positively associated with CT findings of subdural hematoma, intraparenchymal contusion, and mass effect and negatively associated with age, alcoholism, and elevated international normalized ratio. After adjusting for selection bias via propensity score matching, ICP monitor placement was associated with an 8.3 percentage point reduction in the risk-adjusted mortality rate. CONCLUSION: ICP monitor placement occurred in only 46% of eligible patients but was associated with significantly decreased mortality after adjusting for baseline risk profile and the propensity to undergo monitoring. As the individual impact of ICP monitoring may vary, future efforts must determine who stands to benefit from invasive monitoring techniques. (Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.) C1 [Dawes, Aaron J.; Sacks, Greg D.; Cryer, H. Gill; Cohen, Marilyn; Russell, Marcia M.; Maggard-Gibbons, Melinda; Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [McArthur, David L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurosurg, Los Angeles, CA 90095 USA. [Dawes, Aaron J.; Sacks, Greg D.] Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA USA. [Dawes, Aaron J.; Russell, Marcia M.; Maggard-Gibbons, Melinda; Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Gruen, J. Peter] Univ So Calif, Dept Neurosurg, Los Angeles, CA USA. [Preston, Christy; Gorospe, Deidre] Cty Los Angeles, Dept Hlth Serv, Emergency Med Serv Agcy, Los Angeles, CA USA. RP Dawes, AJ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Ronald Reagan UCLA Med Ctr, 757 Westwood Plaza B7-11, Los Angeles, CA 90095 USA. EM adawes@mednet.ucla.edu OI Dawes, Aaron/0000-0003-4574-6765 FU VA Office of Academic Affiliations through the VA/Robert Wood Johnson Clinical Scholars Program FX A.J.D. was supported by the VA Office of Academic Affiliations through the VA/Robert Wood Johnson Clinical Scholars Program. NR 24 TC 11 Z9 11 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD MAR PY 2015 VL 78 IS 3 BP 492 EP 501 DI 10.1097/TA.0000000000000559 PG 10 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA CE8DQ UT WOS:000352072000011 PM 25710418 ER PT J AU King, DR Larentzakis, A Ramly, EP AF King, David Richard Larentzakis, Andreas Ramly, Elie P. CA Boston Trauma Collaborative TI Tourniquet use at the Boston Marathon bombing: Lost in translation SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Tourniquet; bomb; Boston; extremity; prehospital ID RESUSCITATION OUTCOMES CONSORTIUM; OPERATION IRAQI FREEDOM; HEMORRHAGE CONTROL; MULTICENTER EVALUATION; PREHOSPITAL MODE; SEVERE INJURY; LIMB TRAUMA; TRANSPORT; SURVIVAL; EXPERIENCE AB BACKGROUND: The Boston Marathon bombing was the first major, modern US terrorist event with multiple, severe lower extremity injuries. First responders, including trained professionals and civilian bystanders, rushed to aid the injured. The purpose of this review was to determine how severely bleeding extremity injuries were treated in the prehospital setting in the aftermath of the Boston Marathon bombing. METHODS: A database was created and populated by all the Boston Level I trauma centers following the Boston Marathon bombing. Data regarding specific injuries, extremities affected, demographics, prehospital interventions (including tourniquet types), and outcomes were extracted. RESULTS: Of 243 injured, 152 patients presented to the emergency department within 24 hours. Of these 152 patients, there were 66 (63.6% female) experiencing at least one extremity injury, with age ranging from younger than 15 years to 71 years, and with a median Injury Severity Score (ISS) of 10 (range, 1-38). Of the 66 injured patients, 4 had upper limbs affected, 56 had injuries on the lower limbs only, and 6 had combined upper and lower limbs affected. The extremity Abbreviated Injury Scale (AIS) scores had a median of 3 (range, 1-4). There were 17 lower extremity traumatic amputations in 15 patients. In addition, there were 10 patients with 12 lower extremities experiencing major vascular injuries. Of 66 injured patients, 29 patients had recognized extremity exsanguination at the scene. In total, 27 tourniquets were applied: 16 of 17 traumatic amputations, 5 of 12 lower extremities with major vascular injuries, and 6 additional limbs with major soft tissue injury. All tourniquets were improvised, and no commercial, purpose-designed tourniquets were identified. Among all 243 patients, mortality was 0%. CONCLUSION: After the Boston Marathon bombings, extremity exsanguination at the point of injury was either left untreated or treated with an improvised tourniquet in the prehospital environment. An effective, prehospital extremity hemorrhage control posture should be translated to all civilian first responders in the United States and should mirror the military's posture toward extremity bleeding control. The prehospital response to extremity exsanguination after the Boston Marathon bombing demonstrates that our current practice is an approach, lost in translation, from the battlefield to the homeland. (Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.) C1 [King, David Richard; Larentzakis, Andreas; Ramly, Elie P.; Boston Trauma Collaborative] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Trauma,Emergency Surg,Surg Crit Care, Boston, MA 02141 USA. RP King, DR (reprint author), Harvard Univ, Sch Med, US Army Joint Special Operat Command, Massachusetts Gen Hosp,Div Trauma Emergency Surg, 165 Cambridge St,Suite 810, Boston, MA 02141 USA. EM dking3@mgh.harvard.edu OI King, David/0000-0003-1028-1478 NR 28 TC 12 Z9 12 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD MAR PY 2015 VL 78 IS 3 BP 594 EP 599 DI 10.1097/TA.0000000000000561 PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA CE8DQ UT WOS:000352072000027 PM 25710432 ER PT J AU Rago, AP Marini, J Duggan, MJ Beagle, J Runyan, G Sharma, U Peev, M King, DR AF Rago, Adam P. Marini, John Duggan, Michael J. Beagle, John Runyan, Gem Sharma, Upma Peev, Miroslav King, David R. TI Diagnosis and deployment of a self-expanding foam for abdominal exsanguination: Translational questions for human use SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE War; prehospital; hemorrhage; exsanguination; abdominal; foam; swine ID COMBAT CASUALTY CARE; PREHOSPITAL TREATMENT; CLOSED-ABDOMEN; HEMORRHAGE; ULTRASOUND; MODEL; SURVIVAL; WOUNDS; LETHAL; DEATH AB BACKGROUND: We have previously described the hemostatic efficacy of a self-expanding polyurethane foam in lethal venous and arterial hemorrhage models. A number of critical translational questions remain, including prehospital diagnosis of hemorrhage, use with diaphragmatic injury, effects on spontaneous respiration, the role of omentum, and presence of a laparotomy on foam properties. METHODS: In Experiment 1, diagnostic blood aspiration was attempted through a Veress needle before foam deployment during exsanguination (n = 53). In Experiment 2: a lethal hepatoportal injury/diaphragmatic laceration was created followed by foam (n = 6) or resuscitation (n = 10). In Experiment 3, the foam was deployed in naive, spontaneously breathing animals (n = 7), and respiration was monitored. In Experiments 4 and 5, the foam was deployed above (n = 6) and below the omentum (n = 6) and in naive animals (n = 6). Intra-abdominal pressure and organ contact were assessed. RESULTS: In Experiment 1, blood was successfully aspirated from a Veress needle in 70% of lethal iliac artery injuries and 100% of lethal hepatoportal injuries. In Experiment 2, in the presence of a diaphragm injury, between 0 cc and 110 cc of foam was found within the pleural space. Foam treatment resulted in a survival benefit relative to the control group at 1 hour (p = 0.03). In Experiment 3, hypercarbia was observed: mean (SD) P-CO2 was 48 (9.4) mm Hg at baseline and 65 (14) mm Hg at 60 minutes. In Experiment 4, abdominal omentum seemed to influence organ contact and transport in two foam deployments. In Experiment 5, there was no difference in intra-abdominal pressure following foam deployment in the absence of a midline laparotomy. CONCLUSION: In a series of large animal studies, we addressed key translational issues surrounding safe use of foam treatment. These additional data, from diagnosis to deployment, will guide human experiences with foam treatment for massive abdominal exsanguination where no other treatments are available. (Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.) C1 [Duggan, Michael J.; Beagle, John; Peev, Miroslav; King, David R.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Dept Surg, Boston, MA 02141 USA. [Duggan, Michael J.; Beagle, John; Peev, Miroslav; King, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Rago, Adam P.; Marini, John; Sharma, Upma] Arsenal Med Inc, Watertown, MA USA. RP King, DR (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02141 USA. EM DKING3@mgh.harvard.edu OI King, David/0000-0003-1028-1478 FU DARPA ARO [W911NF-10-C-0089, W911NF-12-C-0066] FX This study was supported by DARPA ARO contracts W911NF-10-C-0089 W911NF-12-C-0066. NR 20 TC 2 Z9 2 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD MAR PY 2015 VL 78 IS 3 BP 607 EP 613 DI 10.1097/TA.0000000000000558 PG 7 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA CE8DQ UT WOS:000352072000029 PM 25710434 ER PT J AU Purschke, M Chuang, G Le, M Manstein, D Avram, M Anderson, RR AF Purschke, Martin Chuang, Gary Le, Monica Manstein, Dieter Avram, Mathew Anderson, R. Rox TI LIDOCAINE-INDUCED POTENTIATION OF THERMAL DAMAGE IN KERATINOCYTES, FIBROBLASTS, AND BASAL CELL CARCINOMA IN CULTURE SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2015 VL 47 SU 26 MA 5 BP 2 EP 3 PG 2 WC Dermatology; Surgery SC Dermatology; Surgery GA CE8NN UT WOS:000352099900006 ER PT J AU Wang, YC Gu, Y Dai, TH AF Wang, Yucheng Gu, Ying Dai, Tianhong TI ANTIMICROBIAL BLUE LIGHT INACTIVATION OF MULTIDRUG-RESISTANT ACINETOBACTER BAUMANNII BIOFILMS SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Chinese Peoples Liberat Army Gen Hosp, Beijing 100853, Peoples R China. 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 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2015 VL 47 SU 26 MA 7 BP 3 EP 3 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA CE8NN UT WOS:000352099900008 ER PT J AU Wang, RS Ortega-Martinez, A Purschke, M Zhu, H Anderson, RR Kochevar, I Franco, W AF Wang, Ruisheng Ortega-Martinez, Antonio Purschke, Martin Zhu, Hong Anderson, R. Rox Kochevar, Irene Franco, Walfre TI COLLAGEN CROSS-LINKS AS FLUORESCENT MARKER FOR BIOMECHANICAL CHARACTERIZATION OF COLLAGENOUS TISSUES: FEASIBILITY STUDY SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Clarkson Univ, Potsdam, NY USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2015 VL 47 SU 26 MA 18 BP 7 EP 7 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA CE8NN UT WOS:000352099900019 ER PT J AU Fan, B Neel, V Yaroslavsky, A AF Fan, Bo Neel, Victor Yaroslavsky, Anna TI COMBINING TERAHERTZ PULSED IMAGING IN FREQUENCY DOMAIN AND POLARIZATION OPTICAL IMAGING FOR DELINEATING NONMELANOMA SKIN CANCERS SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Univ Massachusetts, Adv Biophoton Lab, Lowell, MA 01854 USA. Massachusetts Gen Hosp Boston, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2015 VL 47 SU 26 MA 32 BP 11 EP 11 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA CE8NN UT WOS:000352099900032 ER PT J AU Erlendsson, AM Doukas, AG Farinelli, WA Bhayana, B Anderson, RR Haedersdal, M AF Erlendsson, Andres M. Doukas, Apostolos G. Farinelli, William A. Bhayana, Brijesh Anderson, R. Rox Haedersdal, Merete TI PRESSURE ENHANCES FRACTIONAL LASER-ASSISTED DRUG DELIVERY SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. Univ Copenhagen, Bispebjerg Univ Hosp, Copenhagen, Denmark. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2015 VL 47 SU 26 MA 86 BP 30 EP 30 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA CE8NN UT WOS:000352099900086 ER PT J AU Erlendsson, AM Doukas, AG Farinelli, WA Eriksson, AH Zibert, JR Anderson, RR Haedersdal, M AF Erlendsson, Andres M. Doukas, Apostolos G. Farinelli, William A. Eriksson, Andre H. Zibert, John R. Anderson, R. Rox Haedersdal, Merete TI RAPID DERMAL DEPOSITION OF INGENOL MEBUTATE USING PRESSURE AND ABLATIVE FRACTIONAL LASER SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. LEO Pharma AS, Ballerup, Denmark. Univ Copenhagen, Bispebjerg Univ Hosp, Copenhagen, Denmark. 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 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2015 VL 47 SU 26 MA 87 BP 30 EP 30 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA CE8NN UT WOS:000352099900087 ER PT J AU Kositratna, G Manstein, D AF Kositratna, Garuna Manstein, Dieter TI RAPID FIBRIN PLUG FORMATION WITHIN ABLATIVE FRACTIONAL CO2 LASER LESIONS SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 [Kositratna, Garuna; Manstein, Dieter] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2015 VL 47 SU 26 MA 88 BP 30 EP 31 PG 2 WC Dermatology; Surgery SC Dermatology; Surgery GA CE8NN UT WOS:000352099900088 ER PT J AU Wang, Y Gutierrez-Herrera, E Ortega-Martinez, A Farinelli, B Doukas, A Anderson, RR Franco, W AF Wang, Ying Gutierrez-Herrera, Enoch Ortega-Martinez, Antonio Farinelli, Bill Doukas, Apostolos Anderson, R. Rox Franco, Walfre TI UV FLUORESCENCE EXCITATION IMAGING IN WOUND HEALING: WOUND SIZE AND WOUND CLOSURE MEASUREMENTS SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 [Wang, Ying; Gutierrez-Herrera, Enoch; Ortega-Martinez, Antonio; Farinelli, Bill; Doukas, Apostolos; Anderson, R. Rox; Franco, Walfre] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2015 VL 47 SU 26 MA 146 BP 49 EP 49 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA CE8NN UT WOS:000352099900145 ER PT J AU Levin, Y Kositratna, G Evers, M Manstein, D AF Levin, Yakir Kositratna, Garuna Evers, Michael Manstein, Dieter TI OPTIMIZATION OF LASER EXPOSURE PARAMETERS IN FRACTIONAL PHOTOTHERMOLYSIS TO AVOID BULK HEATING SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 [Levin, Yakir; Kositratna, Garuna; Evers, Michael; Manstein, Dieter] Boston Univ, Massachusetts Gen Hosp, Boston, MA 02215 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 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2015 VL 47 SU 26 MA 155 BP 52 EP 52 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA CE8NN UT WOS:000352099900154 ER PT J AU Zhang, W Oda, T Yu, Q Jin, JO AF Zhang, Wei Oda, Tatsuya Yu, Qing Jin, Jun-O TI Fucoidan from Macrocystis pyrifera Has Powerful Immune-Modulatory Effects Compared to Three Other Fucoidans SO MARINE DRUGS LA English DT Article ID ASCOPHYLLUM-NODOSUM; DENDRITIC CELLS; SCAVENGER RECEPTOR; ADAPTIVE IMMUNITY; BROWN SEAWEEDS; MATURATION; NEUTROPHILS; CYTOKINES; INNATE; POLYSACCHARIDE AB Fucoidan, a sulfated polysaccharide purified from brown algae, has a variety of immune-modulation effects, such as promoting activation of dendritic cells (DCs), natural killer (NK) cells and T cells, and enhancing anti-viral and anti-tumor responses. However, the immune-modulatory effect of fucoidan from different seaweed extracts has not been thoroughly analyzed and compared. We analyzed fucoidans obtained from Ascophyllum nodosum (A. nodosum), Macrocystis pyrifera (M. pyrifera), Undaria pinnatifida (U. pinnatifida) and Fucus vesiculosus (F. vesiculosus) for their effect on the apoptosis of human neutrophils, activation of mouse NK cells, maturation of spleen DCs, proliferation and activation of T cells, and the adjuvant effect in vivo. Fucoidans from M. pyrifera and U. pinnatifida strongly delayed human neutrophil apoptosis at low concentration, whereas fucoidans from A. nodosum and F. vesiculosus delayed human neutrophil apoptosis at higher concentration. Moreover, fucoidan from M. pyrifera promoted NK cell activation and cytotoxic activity against YAC-1 cells. In addition, M. pyrifera fucoidan induced the strongest activation of spleen DCs and T cells and ovalbumin (OVA) specific immune responses compared to other fucoidans. These data suggest that fucoidan from M. pyrifera can be potentially useful as a therapeutic agent for infectious diseases, cancer and an effective adjuvant for vaccine. C1 [Zhang, Wei; Jin, Jun-O] Fudan Univ, Shanghai Med Coll, Shanghai Publ Hlth Clin Ctr, Shanghai 201508, Peoples R China. [Oda, Tatsuya] Nagasaki Univ, Div Biochem, Fac Fisheries, Nagasaki, Nagasaki 8528521, Japan. [Yu, Qing] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA 02142 USA. RP Jin, JO (reprint author), Fudan Univ, Shanghai Med Coll, Shanghai Publ Hlth Clin Ctr, Shanghai 201508, Peoples R China. EM weiwei061215@126.com; t-oda@nagasaki-u.ac.jp; qyu@forsyth.org; junojin1@gmail.com FU Research fund for International Young Scientists from National Natural Science Foundation of China [81450110090]; Nagasaki University Major Research Project (Research Initiative for Adaptation to Future Ocean Change) FX We thank the Shanghai Public Health Clinical Center animal facility for maintaining animals. This study was supported by Research fund for International Young Scientists from National Natural Science Foundation of China (81450110090). Tatsuya Oda was supported by a fund from Nagasaki University Major Research Project (Research Initiative for Adaptation to Future Ocean Change). NR 28 TC 8 Z9 9 U1 11 U2 42 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-3397 J9 MAR DRUGS JI Mar. Drugs PD MAR PY 2015 VL 13 IS 3 BP 1084 EP 1104 DI 10.3390/md13031084 PG 21 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA CE6EW UT WOS:000351930500001 PM 25706632 ER PT J AU Bruinsma, BG Uygun, K Yarmush, ML Saeidi, N AF Bruinsma, Bote G. Uygun, Korkut Yarmush, Martin L. Saeidi, Nima TI Surgical models of Roux-en-Y gastric bypass surgery and sleeve gastrectomy in rats and mice SO NATURE PROTOCOLS LA English DT Article ID INTENSIVE MEDICAL THERAPY; BARIATRIC SURGERY; ENERGY-EXPENDITURE; MOUSE MODEL; OBESE RATS; METAANALYSIS; MORTALITY; WEIGHT; TRENDS; PREVALENCE AB Bariatric surgery is the only definitive solution currently available for the present obesity pandemic. These operations typically involve reconfiguration of gastrointestinal tract anatomy and impose profound metabolic and physiological benefits, such as substantially reducing body weight and ameliorating type II diabetes. Therefore, animal models of these surgeries offer unique and exciting opportunities to delineate the underlying mechanisms that contribute to the resolution of obesity and diabetes. Here we describe a standardized procedure for mouse and rat models of Roux-en-Y gastric bypass (80-90 min operative time) and sleeve gastrectomy (30-45 min operative time), which, to a high degree, resembles operations in humans. We also provide detailed protocols for both pre- and postoperative techniques that ensure a high success rate in the operations. These protocols provide the opportunity to mechanistically investigate the systemic effects of the surgical interventions, such as regulation of body weight, glucose homeostasis and gut microbiome. C1 [Bruinsma, Bote G.; Uygun, Korkut; Yarmush, Martin L.; Saeidi, Nima] Massachusetts Gen Hosp, Dept Surg, Ctr Engn Med, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Massachusetts Gen Hosp, Dept Surg, Ctr Engn Med, Boston, MA 02114 USA. EM myarmush@mgh.harvard.edu; nsaeidi@mgh.harvard.edu FU US National Institutes of Health [DK095558] FX This work was supported by US National Institutes of Health grant no. DK095558 to N.S. NR 38 TC 5 Z9 5 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 EI 1750-2799 J9 NAT PROTOC JI Nat. Protoc. PD MAR PY 2015 VL 10 IS 3 DI 10.1038/nprot.2015.027 PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CE6FE UT WOS:000351931300010 PM 25719268 ER PT J AU Bruinsma, BG Berendsen, TA Izamis, ML Yeh, H Yarmush, ML Uygun, K AF Bruinsma, Bote G. Berendsen, Tim A. Izamis, Maria-Louisa Yeh, Heidi Yarmush, Martin L. Uygun, Korkut TI Supercooling preservation and transplantation of the rat liver SO NATURE PROTOCOLS LA English DT Article ID SUBNORMOTHERMIC MACHINE PERFUSION; COLD-STORAGE; POLYETHYLENE-GLYCOL; CARDIAC DEATH; DONOR; INJURY; MODEL; HEPATOCYTES; TEMPERATURE; STRATEGY AB he current standard for liver preservation involves cooling of the organ on ice (0-4 degrees C). Although it is successful for shorter durations, this method of preservation does not allow long-term storage of the liver. The gradual loss of hepatic viability during preservation puts pressure on organ sharing and allocation, may limit the use of suboptimal grafts and necessitates rushed transplantation to achieve desirable post-transplantation outcomes. In an attempt to improve and prolong liver viability during storage, alternative preservation methods are under investigation. For instance, ex vivo machine perfusion systems aim to sustain and even improve viability by supporting hepatic function at warm temperatures, rather than simply slowing down deterioration by cooling. Here we describe a novel subzero preservation technique that combines ex vivo machine perfusion with cryoprotectants to facilitate long-term supercooled preservation. The technique improves the preservation of rat livers to prolong storage times as much as threefold, which is validated by successful long-term recipient survival after orthotopic transplantation. This protocol describes how to load rat livers with cryoprotectants to prevent both intracellular and extracellular ice formation and to protect against hypothermic injury. Cryoprotectants are loaded ex vivo using subnormothermic machine perfusion (SNMP), after which livers can be cooled to -6 degrees C without freezing and kept viable for up to 96 h. Cooling to a supercooled state is controlled, followed by 3 h of SNSNMP recovery and orthotopic liver transplantation. C1 [Bruinsma, Bote G.; Berendsen, Tim A.; Izamis, Maria-Louisa; Yarmush, Martin L.; Uygun, Korkut] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Ctr Engn Med,Med Sch, Boston, MA 02115 USA. [Bruinsma, Bote G.] Univ Amsterdam, Acad Med Ctr, Dept Surg, Surg Lab, NL-1105 AZ Amsterdam, Netherlands. [Yeh, Heidi] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Ctr Engn Med,Med Sch, Boston, MA 02115 USA. EM ireis@sbi.org; uygun.korkut@mgh.harvard.edu FU US National Institutes of Health [R00DK080942, R01DK096075, R01EB008678]; Shriners Hospitals for Children FX Funding from the US National Institutes of Health (R00DK080942, R01DK096075 and R01EB008678) and the Shriners Hospitals for Children is gratefully acknowledged. NR 31 TC 5 Z9 5 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 EI 1750-2799 J9 NAT PROTOC JI Nat. Protoc. PD MAR PY 2015 VL 10 IS 3 DI 10.1038/nprot.2015.011 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CE6FE UT WOS:000351931300009 PM 25692985 ER PT J AU Brawner, BM Reason, JL Goodman, BA Schensul, JJ Guthrie, B AF Brawner, Bridgette M. Reason, Janaiya L. Goodman, Bridget A. Schensul, Jean J. Guthrie, Barbara TI Multilevel Drivers of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome Among Black Philadelphians Exploration Using Community Ethnography and Geographic Information Systems SO NURSING RESEARCH LA English DT Article DE ethnography; geographic mapping; HIV; public health ID SEXUALLY-TRANSMITTED-DISEASES; AFRICAN-AMERICAN WOMEN; HIV RISK; NEIGHBORHOOD CONTEXT; UNITED-STATES; HEALTH; BEHAVIORS; HIV/AIDS; PREVENTION; MEN AB Background: Unequal human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) distribution is influenced by certain social and structural contexts that facilitate HIV transmission and concentrate HIV in disease epicenters. Thus, one of the first steps in designing effective community-level HIV/AIDS initiatives is to disentangle the influence of individual, social, and structural factors on HIV risk. Combining ethnographic methodology with geographic information systems mapping can allow for a complex exploration of multilevel factors within communities that facilitate HIV transmission in highly affected areas. Objectives: We present the formative comparative community-based case study findings of an investigation of individual-, social-, and structural-level factors that contribute to the HIV/AIDS epidemic among Black Philadelphians. Methods: Communities were defined using census tracts. The methodology included ethnographic and geographic information systems mapping, observation, informal conversations with residents and business owners, and secondary analyses of census tract-level data in four Philadelphia neighborhoods. Results: Factors such as overcrowding, disadvantage, permeability in community boundaries, and availability and accessibility of health-related resources varied significantly. Furthermore, HIV/AIDS trended with social and structural inequities above and beyond the community's racial composition. Discussion: This study was a first step to disentangle relationships between community-level factors and potential risk for HIV in an HIV epicenter. The findings also highlight stark sociodemographic differences within and across racial groups and further substantiate the need for comprehensive, community-level HIV prevention interventions. These findings from targeted U.S. urban communities have potential applicability for examining the distribution of HIV/AIDS in broader national and international geosocial contexts. C1 [Brawner, Bridgette M.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Ctr Global Womens Hlth,Nursing, Philadelphia, PA 19104 USA. [Brawner, Bridgette M.; Reason, Janaiya L.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Ctr Global Womens Hlth, Philadelphia, PA 19104 USA. [Goodman, Bridget A.] Nazarbayev Univ, Grad Sch Educ, Astana, Kazakhstan. [Schensul, Jean J.] Inst Community Res, Hartford, CT USA. [Guthrie, Barbara] Northeastern Univ, Nursing PhD Program, Boston, MA 02115 USA. RP Brawner, BM (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Ctr Global Womens Hlth, 418 Curie Blvd,4th Floor,Room 419, Philadelphia, PA 19104 USA. EM brawnerb@nursing.upenn.edu FU National Institute of Mental Health [R25MH087217] FX The authors acknowledge that this study was funded by pilot funding awarded to Dr. Brawner through the National Institute of Mental Health R25MH087217 (Guthrie, Schensul, and Singer [PIs]). NR 53 TC 2 Z9 2 U1 3 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-6562 EI 1538-9847 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2015 VL 64 IS 2 BP 100 EP 110 DI 10.1097/NNR.0000000000000076 PG 11 WC Nursing SC Nursing GA CE2GS UT WOS:000351633500372 PM 25738621 ER PT J AU Callans, K Carroll, D McDonough, A Miller, B Kelleher, A Flanagan, J Bleiler, C AF Callans, Kevin Carroll, Diane McDonough, Annette Miller, Brenda Kelleher, Arlene Flanagan, Jane Bleiler, Carolyn TI Family Experience in Caring for Their Child With an Artificial Airway in the Home SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Callans, Kevin; Carroll, Diane; Miller, Brenda; Kelleher, Arlene; Flanagan, Jane; Bleiler, Carolyn] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McDonough, Annette] Univ Massachusetts Lowell, Lowell, MA USA. 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 0029-6562 EI 1538-9847 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2015 VL 64 IS 2 BP E54 EP E54 PG 1 WC Nursing SC Nursing GA CE2GS UT WOS:000351633500142 ER PT J AU Griffith, C AF Griffith, Catherine TI Frail Older Adults' Experience of Participating in Clinical Trials SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Griffith, Catherine] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0029-6562 EI 1538-9847 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2015 VL 64 IS 2 BP E126 EP E126 PG 1 WC Nursing SC Nursing GA CE2GS UT WOS:000351633500336 ER PT J AU Kim, M Lee, H Cooley, M Sheldon, L AF Kim, MinJin Lee, Haeok Cooley, Mary Sheldon, Lisa TI Attitude Toward HPV Vaccination Among Adolescents and Young Adults: Concept Inventing and Situation-Specific Theory SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Kim, MinJin; Lee, Haeok; Sheldon, Lisa] Univ Massachusetts Boston, Boston, MA USA. [Cooley, Mary] Dana Farber Canc Inst, Boston, MA USA. 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 0029-6562 EI 1538-9847 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2015 VL 64 IS 2 BP E60 EP E60 PG 1 WC Nursing SC Nursing GA CE2GS UT WOS:000351633500158 ER PT J AU Nipp, RD Ryan, DP AF Nipp, Ryan D. Ryan, David P. TI Should FOLFOXIRI Plus Bevacizumab Be the Standard First-Line Therapy in Metastatic Colorectal Cancer? SO ONCOLOGIST LA English DT Editorial Material ID PHASE-III TRIAL; INFUSIONAL FLUOROURACIL; OXALIPLATIN; FOLFIRI; CHEMOTHERAPY; LEUCOVORIN; STATISTICS; IRINOTECAN; CETUXIMAB; RESECTION C1 [Nipp, Ryan D.; Ryan, David P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Nipp, RD (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM rnipp@partners.org NR 24 TC 3 Z9 3 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD MAR PY 2015 VL 20 IS 3 BP 236 EP 238 DI 10.1634/theoncologist.2014-0495 PG 3 WC Oncology SC Oncology GA CE6BB UT WOS:000351919500002 PM 25660156 ER PT J AU Mulcahey, MK Campbell, KJ Golijanan, P Gross, D Provencher, MT AF Mulcahey, Mary K. Campbell, Kevin J. Golijanan, Petar Gross, Daniel Provencher, Matthew T. TI Posterior Bone Grafting for Glenoid Defects of the Shoulder SO OPERATIVE TECHNIQUES IN SPORTS MEDICINE LA English DT Article DE bone graft; posterior glenoid defect ID RECURRENT ANTERIOR DISLOCATION; GLENOHUMERAL JOINT; POSTEROINFERIOR INSTABILITY; ARTHROSCOPIC MANAGEMENT; EXCESSIVE RETROVERSION; JERK TEST; SUBLUXATION; STABILITY; LESION; DIAGNOSIS AB Posterior shoulder instability is a challenging clinical entity that requires a comprehensive history and physical examination, as well as relevant imaging studies, to confidently make the diagnosis. Posterior shoulder instability may cause significant shoulder dysfunction and pain. Several anatomical features contribute to posterior instability, including soft tissue lesions and posterior glenoid bone loss. Posterior shoulder stabilization with bone graft transfer procedures and glenoid osteotomies to restore the normal glenohumeral arc have been revisited in recent years to address posterior glenoid bone erosion and glenoid version issue. This review article provides a comprehensive description of posterior shoulder instability with a focus on the treatment of posterior glenoid bone defects and glenoid version issues. (C) 2015 Elsevier Inc. All rights reserved. C1 [Mulcahey, Mary K.] Drexel Univ, Hahnemann Univ Hosp, Coll Med, Dept Orthopaed Surg, Philadelphia, PA 19102 USA. [Campbell, Kevin J.] Rush Univ, Univ Med Ctr, Dept Orthopaed, Chicago, IL 60612 USA. [Golijanan, Petar; Gross, Daniel] Massachusetts Gen Hosp, Sports Med & Surg, Boston, MA 02114 USA. [Provencher, Matthew T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Sports Med & Surg, Boston, MA 02115 USA. RP Mulcahey, MK (reprint author), Drexel Univ, Hahnemann Univ Hosp, Coll Med, Dept Orthopaed Surg, 245 N 15th St,Mail Stop 420, Philadelphia, PA 19102 USA. EM mary.mulcahey.md@gmail.com NR 67 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1060-1872 EI 1557-9794 J9 OPER TECHN SPORT MED JI Oper. Tech. Sports Med. PD MAR PY 2015 VL 23 IS 1 BP 32 EP 42 DI 10.1053/j.otsm.2014.09.011 PG 11 WC Sport Sciences; Surgery SC Sport Sciences; Surgery GA CE4FN UT WOS:000351786600006 ER PT J AU Choi, HR Siliski, JM Malchau, H Kwon, YM AF Choi, Ho-Rim Siliski, John M. Malchau, Henrik Kwon, Young-Min TI Effect of Repeated Manipulation on Range of Motion in Patients With Stiff Total Knee Arthroplasty SO ORTHOPEDICS LA English DT Article ID FLEXION; ANESTHESIA; MANAGEMENT; TKA AB Although manipulation under anesthesia (MUA) has been considered effective first-line treatment for stiff total knee arthroplasty (TKA), there is no consensus regarding the usefulness of repeated MUA. The purpose of this study was to investigate the usefulness of repeated MUA performed for patients in whom satisfactory range of motion (ROM) was not achieved by MUA. The authors retrospectively reviewed 15 patients who underwent repeated MUA after failure of initial MUA for stiff TKA. Demographic and ROM data were collected. A final ROM of less than 90 degrees was considered a failed manipulation (failure group) and a final ROM of 90 degrees or more was considered a successful manipulation (success group). Average pre-repeated MUA ROM (72.3 degrees +/- 19.5 degrees) immediately improved to 112.3 degrees +/- 9.7 degrees (P<.001) in the operating room, and final ROM was 89.6 degrees +/- 23.9 degrees, an overall gain of 17.3 degrees (P=.04). However, despite this overall ROM increase, a successful final ROM (90 degrees or more) was achieved in approximately half of patients (7 of 13; 54%). There were no significant differences in demographics between the success and failure groups, except that there was significantly less pre-TKA ROM in the failure group (P=.02). There were no complications related to either the first or the repeated MUA procedures. The findings of this study suggest that repeated MUA can improve overall ROM for stiff TKA. The success rate of repeated MUA was less than that of primary MUA; however, it is a useful treatment modality for stiff TKA. Decreased pre-TKA ROM appeared to be associated with poor outcomes after repeated MUA. C1 Massachusetts Gen Hosp, Harris Orthoped Lab, Boston, MA 02114 USA. [Kwon, Young-Min] Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. RP Kwon, YM (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, 55 Fruit St,Yawkey 3B, Boston, MA 02114 USA. EM kwon.young-min@mgh.harvard.edu FU Biomet; Stryker FX Drs Choi, Malchau, and Kwon have no relevant financial relationships to disclose. Dr Siliski is a paid consultant for Biomet and Stryker. NR 12 TC 1 Z9 2 U1 1 U2 3 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 EI 1938-2367 J9 ORTHOPEDICS JI Orthopedics PD MAR PY 2015 VL 38 IS 3 BP E157 EP E162 DI 10.3928/01477447-20150305-51 PG 6 WC Orthopedics SC Orthopedics GA CE9HT UT WOS:000352155600002 PM 25760501 ER PT J AU Parisi, T Burroughs, B Kwon, YM AF Parisi, Thomas Burroughs, Brian Kwon, Young-Min TI Modular Hip Implant Fracture at the Stem-Sleeve Interface SO ORTHOPEDICS LA English DT Article ID FEMORAL STEMS; FRETTING WEAR; FAILURE; NECK; ARTHROPLASTY; PROSTHESIS; COMPONENT; JUNCTION AB The use of modular implants in femoral stem design has grown increasingly popular over the last decade because of the theoretical advantage of more flexibility and optimization of femoral anteversion, limb length, and femoral component offset. With the benefit of increased surgical flexibility, however, modularity also carries the theoretical risks of fretting at the modular surfaces, sequelae of wear debris, and possible failure and fracture of the stem at the modular junction. Indeed, there have been an increasing number of reports of modular implants failing due to fracture at modular junctions. The S-ROM prosthesis (DePuy Orthopaedics, Inc, Warsaw, Indiana), however, has a stellar clinical record and has been used with good results in both primary and revision total hip arthroplasty. Only a single case of S-ROM failure at the stem-sleeve interface has been reported in the orthopedic literature. The aim of this case report was to present a succinct history of proximal modularity in total hip arthroplasty and to describe the only known case of this type of catastrophic failure in an S-ROM prosthesis with a metal-on-metal bearing. Despite a low level of serum metal ions on presentation, scanning electron microscopy showed findings consistent with corrosive processes and pseudotumor was seen at revision surgery. C1 [Parisi, Thomas; Burroughs, Brian; Kwon, Young-Min] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Parisi, T (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, 55 Fruit St, Boston, MA 02114 USA. EM tparisi@partners.org NR 22 TC 3 Z9 3 U1 1 U2 9 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 EI 1938-2367 J9 ORTHOPEDICS JI Orthopedics PD MAR PY 2015 VL 38 IS 3 BP E234 EP E239 DI 10.3928/01477447-20150305-91 PG 6 WC Orthopedics SC Orthopedics GA CE9HT UT WOS:000352155600014 PM 25760513 ER PT J AU Manchikanti, L Falco, FJE Helm, S Hirsch, JA AF Manchikanti, Laxmaiah Falco, Frank J. E. Helm, Standiford, II Hirsch, Joshua A. TI First, Do No Harm by Adopting Evidence-Based Policy Initiatives: The Overselling of ICD-10 by Congress with High Expectations SO PAIN PHYSICIAN LA English DT Article ID ELECTRONIC HEALTH RECORDS; UNITED-STATES; IMPLEMENTATION; METAMORPHOSIS; MEDICINE; READY; CARE C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys, Newark, DE USA. [Falco, Frank J. E.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Helm, Standiford, II] Helm Ctr Pain Management, Laguna Hills, CA USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com FU Cephalon/Teva; AstraZeneca; Purdue Pharma, LP FX Dr. Manchikanti has provided limited consulting services to Semnur Pharmaceuticals, Incorporated, which is developing nonparticulate steroids. Dr. Falco is a consultant for St. Jude Medical Inc. and Joimax Inc. Dr. Helm is a clinical investigator with Epimed and receives research support from Cephalon/Teva, AstraZeneca, and Purdue Pharma, LP. He has attended an advisory group meeting for Activas. Dr. Hirsch is a consultant for Medtronic. NR 46 TC 8 Z9 8 U1 0 U2 0 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD MAR-APR PY 2015 VL 18 IS 2 BP E107 EP E113 PG 7 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA CE1GL UT WOS:000351560000010 PM 25794209 ER PT J AU Manchikanti, L Falco, FJE Singh, V Hirsch, JA AF Manchikanti, Laxmaiah Falco, Frank J. E. Singh, Vijay Hirsch, Joshua A. TI Elusive "Doc Fix": Groundhog Day 2015 for Sustainable Growth Rate (SGR) SO PAIN PHYSICIAN LA English DT Article ID ELECTRONIC HEALTH RECORDS; ICD-10; ADOPTION; CARE C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys, Newark, DE USA. [Falco, Frank J. E.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Singh, Vijay] Spine Pain Diagnost Associates, Niagara, WI USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 21 TC 3 Z9 3 U1 0 U2 0 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD MAR-APR PY 2015 VL 18 IS 2 BP E101 EP E105 PG 5 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA CE1GL UT WOS:000351560000009 PM 25794208 ER PT J AU Manchikanti, L Pampati, V Falco, FJE Hirsch, JA AF Manchikanti, Laxmaiah Pampati, Vidyasagar Falco, Frank J. E. Hirsch, Joshua A. TI An Updated Assessment of Utilization of Interventional Pain Management Techniques in the Medicare Population: 2000-2013 SO PAIN PHYSICIAN LA English DT Article DE Chronic pain; chronic spinal pain; interventional pain management; interventional techniques; epidural injections; facet joint interventions; sacroiliac joint injections ID LOW-BACK-PAIN; MANAGING CHRONIC PAIN; UNITED-STATES; EPIDURAL INJECTIONS; GLOBAL BURDEN; HEALTH-STATUS; EPIDEMIOLOGY; PREVALENCE; TRENDS; GROWTH AB Background: The rapid increase in the prevalence of chronic pain and disability, and the explosion of interventional pain management associated health care costs are a major concern for our community. Further, the increasing utilization of numerous modalities of treatments in managing chronic pain, continue to escalate at a pace which may not be sustainable. There are multiple regulations in place to control the growth of health care expenditures which seem to have been largely ineffective. Among the various modalities utilized in managing chronic pain, interventional techniques have shown a significant increase in their utilization in the face of continued debate with respect to the accuracy of diagnostic interventions and the efficacy of therapeutic interventions. Objective: To update and assess the utilization of interventional techniques in chronic pain management in fee-for-service Medicare population. Study Design: An updated analysis of the growth of interventional techniques in managing chronic pain in fee-for-service Medicare beneficiaries from 2000 through 2013. Methods: The data were derived and analyzed utilizing the Centers for Medicare and Medicaid Services (CMS) Physician Supplier Procedure Summary Master Data from 2000 through 2013. Results: From 2000 through 2013, in fee-for-service Medicare beneficiaries, the overall utilization of interventional techniques services increased 236% at an annual average growth of 9.8%, whereas the per 100,000 Medicare population utilization increased 156% with an annual average growth of 7.5%. During this period, the US population increased 12% with an annual average increase of 0.9%, whereas those above 65 years of age increased 27% with an annual average increase of 1.9%. Total Medicare beneficiaries increased 31% with an annual average increase of 2.1%, with an overall increase of 64% for those above 65 years of age, an increase of 26%, constituting 17% of the US population in 2013. The overall increases in epidural and adhesiolysis procedures were 165% compared to 102% per 100,000 fee-for-service population with annual average increases of 7.8% and 5.6%. Facet joint and sacroiliac joint injections increased 417% for services with an annual average increase of 13.5%, whereas the rate per 100,000 fee-for-service Medicare beneficiaries increased 295% with an annual average increase of 11.1%. Limitations: Limitations of this assessment include the lack of inclusion of participants from Medicare Advantage plans, lack of appropriate available data for state-wide utilization, and potential errors in documentation, coding, and billing. Conclusion: This update once again shows a significant increase in interventional techniques in fee-for-service Medicare beneficiaries from 2000 through 2013 with an increase of 156% per 100,000 Medicare population with an annual average increase of 7.5%. During this period the Medicare population increased 31% with an annual average increase of 2.1%. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Pampati, Vidyasagar] Univ Louisville, Louisville, KY 40292 USA. [Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys, Newark, DE USA. [Falco, Frank J. E.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 72 TC 25 Z9 25 U1 1 U2 10 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD MAR-APR PY 2015 VL 18 IS 2 BP E115 EP E127 PG 13 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA CE1GL UT WOS:000351560000011 PM 25794210 ER PT J AU Vedak, P Nazarian, RM Kroshinsky, D AF Vedak, Priyanka Nazarian, Rosalynn M. Kroshinsky, Daniela TI A Case of Eczematid-Like Purpura of Doucas and Kapetanakis in a Child SO PEDIATRIC DERMATOLOGY LA English DT Article AB Eczematid-like purpura of Doucas and Kapetanakis is a subtype of the pigmented purpuric dermatoses, a group of uncommon dermatoses of unclear etiology characterized by purpura, petechiae, and hyperpigmentation. The Doucas and Kapetanakis subtype is rare in children, and its subtle findings can initially be overlooked and mistaken for other, more common dermatologic disorders in this age group. We present a case eczematid-like purpura of Doucas and Kapetanakis in an 11-year-old boy initially treated as eczema. C1 [Vedak, Priyanka; Kroshinsky, Daniela] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02115 USA. [Nazarian, Rosalynn M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. [Nazarian, Rosalynn M.; Kroshinsky, Daniela] Harvard Univ, Sch Med, Boston, MA USA. RP Kroshinsky, D (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02115 USA. EM dkroshinsky@partners.org NR 5 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-8046 EI 1525-1470 J9 PEDIATR DERMATOL JI Pediatr. Dermatol. PD MAR-APR PY 2015 VL 32 IS 2 BP 291 EP 292 DI 10.1111/pde.12507 PG 2 WC Dermatology; Pediatrics SC Dermatology; Pediatrics GA CE3RZ UT WOS:000351747500036 PM 25641544 ER PT J AU Moye, J Rouse, SJ AF Moye, Jennifer Rouse, Susan J. TI Posttraumatic Stress in Older Adults When Medical Diagnoses or Treatments Cause Traumatic Stress SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Posttraumatic stress disorder (PTSD); Geriatric; Cardiac; Cancer ID MYOCARDIAL-INFARCTION; CARDIAC-ARREST; DISORDER; PTSD; VETERANS; SURVIVORS; CANCER; CARE; CONSEQUENCES; COMORBIDITY AB Most older patients adapt after catastrophic medical diagnoses and treatments, but a significant number may develop posttraumatic stress disorder (PTSD) symptoms. PTSD symptoms create added burden for the individual, family, and health care system for the patient's recovery. Medical-related PTSD may be underdiagnosed by providers who may be unaware that these health problems can lead to PTSD symptoms. Treatment research is lacking, but pharmacologic and nonpharmacologic approaches to treatment may be extrapolated and adjusted from the literature focusing on younger adults. Additional study is needed. C1 [Moye, Jennifer; Rouse, Susan J.] VA Boston Healthcare Syst, Brockton, MA 02301 USA. [Moye, Jennifer] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Moye, J (reprint author), VA Boston Healthcare Syst, Brockton Div, 940 Belmont St, Brockton, MA 02301 USA. EM jennifer.moye@va.gov RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X FU Department of Veterans Affairs Rehabilitation Research and Development Service [5101RX000104-02] FX Disclosure: This material is the result of work supported with resources and the use of facilities at the Boston VA Medical Center. Dr J. Moye received funding for research from the Department of Veterans Affairs Rehabilitation Research and Development Service #5101RX000104-02. NR 48 TC 1 Z9 1 U1 2 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0193-953X EI 1558-3147 J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD MAR PY 2015 VL 38 IS 1 BP 45 EP 57 DI 10.1016/j.psc.2014.11.003 PG 13 WC Psychiatry SC Psychiatry GA CE4MM UT WOS:000351804700004 PM 25725568 ER PT J AU Stoddard, FJ Ryan, CM Schneider, JC AF Stoddard, Frederick J., Jr. Ryan, Colleen M. Schneider, Jeffrey C. TI Physical and Psychiatric Recovery from Burns SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Rehabilitation; Resilience; Recovery; Body image; Posttraumatic stress disorder; Depression; Hypertrophic scar; Burn reconstruction ID SPINAL-CORD-INJURY; HETEROTOPIC BONE-FORMATION; ELECTRICAL BURNS; HEALED BURNS; DOUBLE-BLIND; HIP-REPLACEMENT; GROWTH-HORMONE; FOLLOW-UP; CHILDREN; OSSIFICATION AB Burn injuries pose complex biopsychosocial challenges to recovery and improved comprehensive care. The physical and emotional sequelae of burns differ, depending on burn severity, individual resilience, and stage of development when they occur. Most burn survivors are resilient and recover, whereas some are more vulnerable and have complicated outcomes. Physical rehabilitation is affected by orthopedic, neurologic, and metabolic complications and disabilities. Psychiatric recovery is affected by pain, mental disorders, substance abuse, and burn stigmatization. Individual resilience, social supports, and educational or occupational achievements affect outcomes. C1 [Stoddard, Frederick J., Jr.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ryan, Colleen M.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Schneider, Jeffrey C.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Boston, MA 02129 USA. RP Schneider, JC (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, 300 1st Ave, Boston, MA 02129 USA. EM jcschneider@partners.org NR 103 TC 1 Z9 1 U1 4 U2 17 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0193-953X EI 1558-3147 J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD MAR PY 2015 VL 38 IS 1 BP 105 EP 120 DI 10.1016/j.psc.2014.11.001 PG 16 WC Psychiatry SC Psychiatry GA CE4MM UT WOS:000351804700008 PM 25725572 ER PT J AU Saffer, BY Lanting, SC Koehle, MS Klonsky, ED Iverson, GL AF Saffer, Boaz Y. Lanting, Shawnda C. Koehle, Michael S. Klonsky, E. David Iverson, Grant L. TI Assessing cognitive impairment using PROMIS (R) applied cognition-abilities scales in a medical outpatient sample SO PSYCHIATRY RESEARCH LA English DT Article DE Patient-Reported Outcomes Measurement Information System (PROMIS (R)); Self-reported cognition; Depression; Anxiety ID GENERALIZED ANXIETY DISORDER; PATIENT-REPORTED OUTCOMES; DEPRESSION; GAD-7 AB Having a brief, standardized, reliable, and valid self-rated test of perceived cognitive functioning could be beneficial in psychiatry clinical practice, research, and clinical trials. The PROMIS (R) Applied Cognition-Abilities scales were developed, evaluated, and distributed by the National Institutes of Health to measure perceived cognitive functioning. This study examines several aspects of the reliability and validity of the PROMIS (R) Applied Cognition-Abilities eight and four-item scales in a sample of adult and older adult medical outpatients (N=148). Internal consistency reliability was high for both PROMIS (R) cognition scales. The brief four-item scale was highly correlated with the full eight-item scale (r(s)=0.98). There was a moderate correlation between the PROMIS (R) Applied Cognition-Abilities scales and measures of depression (PHQ-9) and anxiety (GAD-7). Subgroups of participants screening positively for depression or anxiety reported significantly worse cognitive functioning than medical controls, with large effect sizes. The base rates of individual items endorsed by depressed, anxious, and control participants are reported. More than 42% of depressed and anxious participants reported problems with their memory and concentration compared with fewer than 8% of medical controls. The field would benefit from studies using the PROMIS (R) Applied Cognition-Abilities scales in more demographically diverse samples and with other established measures of cognition. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Saffer, Boaz Y.; Lanting, Shawnda C.; Koehle, Michael S.; Iverson, Grant L.] Copeman Healthcare Ctr, Vancouver, BC, Canada. [Saffer, Boaz Y.; Klonsky, E. David] Univ British Columbia, Dept Psychol, Vancouver, BC V6T 1Z4, Canada. [Lanting, Shawnda C.; Koehle, Michael S.] Univ British Columbia, Sch Kinesiol, Vancouver, BC V6T 1Z4, Canada. [Koehle, Michael S.] Univ British Columbia, Div Sport Med, Dept Family Practice, Vancouver, BC V6T 1Z4, Canada. [Iverson, Grant L.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. RP Saffer, BY (reprint author), Univ British Columbia, Dept Psychol, 2136 West Mall, Vancouver, BC V6T 1Z4, Canada. EM boazsaffer@hotmail.com NR 20 TC 4 Z9 4 U1 1 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAR PY 2015 VL 226 IS 1 BP 169 EP 172 DI 10.1016/j.psychres.2014.12.043 PG 4 WC Psychiatry SC Psychiatry GA CE6SV UT WOS:000351969400024 PM 25639374 ER PT J AU Rai, A Nimeh, T Sood, A Thirumavalavan, N Thurmond, PE Azadzoi, KM Lerner, LB AF Rai, Arun Nimeh, Tony Sood, Akshay Thirumavalavan, Nannan Thurmond, Portia E. Azadzoi, Kazem M. Lerner, Lori B. TI Could Nocturia Be an Indicator of an Undiagnosed Sleep Disorder in Male Veterans? SO UROLOGY LA English DT Article ID CHRONICALLY ISCHEMIC BLADDER; URINARY-TRACT SYMPTOMS; BERLIN QUESTIONNAIRE; OVERACTIVE BLADDER; IDENTIFY PATIENTS; APNEA SYNDROME; SEVERITY; POPULATION; PREVALENCE; FREQUENCY AB OBJECTIVE To determine if men presenting with nocturia and/or voiding complaints may have undiagnosed symptoms of sleep-disordered breathing (SDB). MATERIALS AND METHODS We conducted a cross-sectional study with men presenting to the Veterans Administration Boston Healthcare System Urology clinic between August 2012 and January 2013. Patients were asked to complete the American Urological Association symptom score and the Berlin sleep questionnaire to evaluate their voiding complaints and sleep quality. We performed univariable and multivariable statistical analyses to identify correlations between a positive Berlin score and voiding symptoms, with an emphasis on nocturia. RESULTS A total 618 completed questionnaires were included. More than 65% of patients reported nocturia. Of those reporting nocturia, 55% also had a positive Berlin score. The American Urological Association symptom score components of frequency and nocturia, as well as body mass index and hypertension, were shown to be significant independent predictors of a positive Berlin questionnaire, suggesting high likelihood of SDB. Conversely, a positive Berlin questionnaire was a significant independent predictor of nocturia, suggesting high degree of correlation between the 2 conditions. CONCLUSION Nocturia and other voiding symptoms, such as frequency, predict a positive Berlin score, and vice versa. Patients with a positive Berlin score may have an undiagnosed sleep disorder, the sequelae of which can lead to significant health consequences. If present, treatment of SDB can ameliorate voiding symptoms. Urologists should consider administration of the Berlin score in their office, particularly in patients refractory to treatment for their voiding complaints, and if positive, consider referral to a sleep specialist. Published by Elsevier Inc. C1 Boston Med Ctr, Dept Urol, Boston, MA USA. VA Boston Healthcare Syst, Dept Surg, West Roxbury, MA USA. Vattikuti Urol Inst, Detroit, MI USA. Boston Univ, Sch Med, Dept Urol, Boston, MA 02118 USA. RP Lerner, LB (reprint author), Boston Univ, Sch Med, VA Boston Healthcare Syst, Urol Sect, 12 Water St, Hingham, MA 02043 USA. EM Lerner_lori@hotmail.com FU BLRD VA [I01 BX001428] NR 30 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD MAR PY 2015 VL 85 IS 3 BP 641 EP 646 DI 10.1016/j.urology.2014.10.055 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA CE6JJ UT WOS:000351942400040 PM 25733279 ER PT J AU Barry, MJ AF Barry, Michael J. TI Is New Visual Prostate Symptom Score Useful as International Prostate Symptom Score in the Evaluation of Men With Lower Urinary Tract Symptoms? A Prospective Comparison of 2 Symptom Scores in Turkish Society EDITORIAL COMMENT SO UROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. NR 3 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 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD MAR PY 2015 VL 85 IS 3 BP 657 EP 658 DI 10.1016/j.urology.2014.10.058 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CE6JJ UT WOS:000351942400044 PM 25733283 ER PT J AU Kim, E Lee, Y Lee, S Park, SB AF Kim, Eunha Lee, Youngjun Lee, Sanghee Park, Seung Bum TI Discovery, Understanding, and Bioapplication of Organic Fluorophore: A Case Study with an Indolizine-Based Novel Fluorophore, Seoul-Fluor SO ACCOUNTS OF CHEMICAL RESEARCH LA English DT Review ID FLUORESCENCE PROBES; RATIONAL DESIGN; LIPID DROPLETS; CORE SKELETON; QUANTUM YIELD; DYES; LIGHT; HETEROCYCLES; STRATEGIES; VISCOSITY AB CONSPECTUS: Owing to its high sensitivity and great applicability, the fluorescence phenomenon has been considered as an inevitable research tool in the modem scientific fields of chemistry, biology, materials science, biomedical science, and their interfaces. Many strategies have been pursued to understand and manipulate the photophysical properties of fluorescent materials, but the scientific community has been focused on the repeated application of existing organic fluorophores or the identification of unique fluorescence properties in a trial-and-error basis without systematic studies. Moreover, recent studies are emphasizing the necessity of deeper understanding about the structure photophysical property relationship of organic fluorophores for the development of better fluorescent probes. Herein, we provide an overview of a novel fluorescent molecular framework, Seoul-Fluor, which can be rationally engineered to furnish a wide variety of fluorophores in terms of the photophysical properties. Seoul-Fluor is built on an indolizine-based fluorescent platform with three different positions to introduce various substituents: R-1 and R-2 substituents for electronic perturbation; R-3 substituent as a functional handle for bioconjugation. Over the past decade, we have demonstrated that the Seoul-Fluor system has (i) tunable and predictable emission wavelength covering a full visible-color range; (ii) controllable quantum yield via photoinduced electron transfer phenomenon; and (iii) environment-sensitive fluorogenic properties that can be modified through intramolecular charge transfer processes. We convincingly demonstrated the prediction of photophysical properties, that is, emission wavelength and quantum yield, through the construction of a systematic set of analogues and the subsequent analysis of their photophysical properties without the highly sophisticated theoretical support. Guided, by quantifiable parameters such as the Hammett substituent constants or energy levels of the molecular orbitals, this unique organic fluorophore can serve as a versatile molecular platform for the development of novel fluorescent switchable biosensors and filuorogenic bioprobes. In this Account,;we will discuss the discovery and recent progress made on Seoul-Fluor, the rational design of Seoul-Fluor-based bioprobes, and their practical applications to specific biological processes that are facilitated by systematic studies of the structure photophysical property relationships. C1 [Kim, Eunha] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Kim, Eunha] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lee, Youngjun; Lee, Sanghee; Park, Seung Bum] Seoul Natl Univ, Dept Chem, Ctr Chem Prote, Seoul 151747, South Korea. RP Park, SB (reprint author), Seoul Natl Univ, Dept Chem, Ctr Chem Prote, Seoul 151747, South Korea. EM sbpark@snu.ac.kr FU Creative Research Initiative Grant - National Research Foundation of Korea (NRF) [2014R1A3A2030423]; Bio & Medical Technology Development Program - National Research Foundation of Korea (NRF) [2012M3A9C4048780] FX This work was supported by the Creative Research Initiative Grant (2014R1A3A2030423) and the Bio & Medical Technology Development Program (2012M3A9C4048780) funded by the National Research Foundation of Korea (NRF). E.K and S.L. are grateful for BK21 Postdoctoral Scholarship, and Y.L. is grateful for a BK21 Scholarship. NR 43 TC 27 Z9 27 U1 13 U2 89 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0001-4842 EI 1520-4898 J9 ACCOUNTS CHEM RES JI Accounts Chem. Res. PD MAR PY 2015 VL 48 IS 3 BP 538 EP 547 DI 10.1021/ar500370v PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA CD8EB UT WOS:000351326900006 PM 25695375 ER PT J AU Gandhi, PU Motiwala, SR Belcher, AM Gaggin, HK Weiner, RB Baggish, AL Fiuzat, M Rocca, HPBL Januzzi, JL AF Gandhi, Parul U. Motiwala, Shweta R. Belcher, Arianna M. Gaggin, Hanna K. Weiner, Rory B. Baggish, Aaron L. Fiuzat, Mona Rocca, Hans-Peter Brunner-La Januzzi, James L., Jr. TI Galectin-3 and mineralocorticoid receptor antagonist use in patients with chronic heart failure due to left ventricular systolic dysfunction SO AMERICAN HEART JOURNAL LA English DT Article ID NATRIURETIC PEPTIDE; THERAPY PROTECT; HF-ACTION AB Background Galectin-3 is a prognostic heart failure biomarker associated with aldosterone-induced myocardial fibrosis; mineralocorticoid receptor antagonists (MRAs) may reduce such fibrosis. We sought to examine outcomes of patients with heart failure with reduced ejection fraction (HFrEF) as a function of galectin-3 and MRA therapy. Methods A total of 151 patients with chronic HFrEF were categorized by baseline galectin-3 and subsequent MRA therapy trends with regard to cardiovascular (CV) events, left ventricular remodeling, safely, and quality of life, over a mean of 10 months. Results Although galectin-3 >20 ng/mL was associated with doubling in adjusted risk for CV events, regardless of MRA treatment, there was no difference in CV event rates with regard to MRA use patterns, independent of galectin-3 concentrations. Specifically, in patients with elevated galectin-3 treated with intensified MRA therapy, a significant difference was not detected in CV event rates (P = .79) or the cumulative number of such events (P = .76). Adjusted analysis revealed no difference in time to first CV event if MRA was added/intensified in those with elevated galectin-3 (hazard ratio 0.99, 95% CI 0.97-1.02, P = .74); similarly, cumulative MRA dose was not a specific predictor of benefit. In those with elevated galectin-3, MRA therapy did not affect left ventricular remodeling indices or quality of life at follow-up; these patients had the highest rates of treatment-related adverse events with intensified MRA use. Regardless of MRA use, elevated galectin-3 was associated with more significant renal dysfunction. Conclusions Among patients with chronic HFrEF and elevated galectin-3 concentrations, we found no specific benefit from addition or intensification of MRA therapy. C1 [Gandhi, Parul U.; Belcher, Arianna M.; Gaggin, Hanna K.; Weiner, Rory B.; Baggish, Aaron L.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Motiwala, Shweta R.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Fiuzat, Mona] Duke Univ, Med Ctr, Durham, NC USA. [Rocca, Hans-Peter Brunner-La] Maastricht Univ, Med Ctr, Dept Cardiol, NL-6200 MD Maastricht, Netherlands. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM jjanuzzi@partners.org FU Dennis and Marilyn Barry Fellowship in Cardiology; Clark Fund for Cardiac Research Innovation; Roman W. DeSanctis Clinical Scholar Endowment FX Drs Gandhi and Motiwala are supported by the Dennis and Marilyn Barry Fellowship in Cardiology, Dr Gaggin is supported in part by the Clark Fund for Cardiac Research Innovation, and Dr Januzzi is supported in part by the Roman W. DeSanctis Clinical Scholar Endowment. NR 21 TC 5 Z9 8 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD MAR PY 2015 VL 169 IS 3 BP 404 EP 411 DI 10.1016/j.ahj.2014.12.012 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CE0ID UT WOS:000351486800013 PM 25728731 ER PT J AU Cefalo, P Weinberg, I Hawkins, BM Hariharan, P Okechukwu, I Parry, BA Chang, YC Rosovsky, R Liu, SW Jaff, MR Kabrhel, C AF Cefalo, Philip Weinberg, Ido Hawkins, Beau M. Hariharan, Praveen Okechukwu, Ikenna Parry, Blair A. Chang, Yuchiao Rosovsky, Rachel Liu, Shan W. Jaff, Michael R. Kabrhel, Christopher TI A Comparison of Patients Diagnosed With Pulmonary Embolism Who Are >= 65 Years With Patients < 65 Years SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID DEEP-VEIN THROMBOSIS; NATRIURETIC PEPTIDE LEVELS; LOW-RISK PATIENTS; AGE; PREDICTION; GENDER; IMPACT; OLDER; RULE AB Recent studies have highlighted differences in how older patients respond to high-risk pulmonary embolism (PE) and treatment. However, guidelines for PE risk stratification and treatment are not based on age, and data are lacking for older patients. We characterized the impact of age on clinical features, risk stratification, treatment, and outcomes in a sample of patients with PE in the emergency department. We performed an observational cohort study of 547 consecutive patients with PE in the emergency department from 2005 to 2011 in an urban tertiary hospital. We used bivariate proportions and multivariable logistic regression to compare clinical presentation, risk category, treatment, and outcomes in patients >= 65 years with those <65 years. The mean age was 58 +/- 17 years, 276(50%) were women, and 210 (38%) were >= 65 years. PE was more severe in patients >= 65 years (massive 14% vs 5%, submassive 48% vs 25%, and low risk 38% vs 70%, p <0.0001), with submassive PE being the most common presentation in patients >= 65 years. However, subanalysis removing natriuretic peptides from the definition of submassive PE negated this finding. Treatment with parenteral anticoagulation (88% vs 90%, p = 0.32), thrombolytic therapy (5% vs 4%, p = 0.87), and inferior vena cava filter (4% vs 4%, p = 0.73) were similar among age groups. Patients >= 65 years had higher 30-day mortality (11% vs 3%, p <0.001). In conclusion, patients >= 65 years present with more severe PE and have higher mortality, although treatment patterns were similar to younger patients. Age-specific guideline definitions of submassive PE may better identify high-risk patients. (c) 2015 Elsevier Inc. All rights reserved. C1 [Cefalo, Philip] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Cefalo, Philip; Hariharan, Praveen; Okechukwu, Ikenna; Parry, Blair A.; Rosovsky, Rachel; Liu, Shan W.; Kabrhel, Christopher] Massachusetts Gen Hosp, Dept Emergency Med, Ctr Vasc Emergencies, Boston, MA 02114 USA. [Weinberg, Ido; Jaff, Michael R.] Massachusetts Gen Hosp, Div Cardiol & Vasc Med, Dept Med, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA. [Hawkins, Beau M.] Univ Oklahoma, Hlth Sci Ctr, Cardiovasc Dis Sect, Dept Internal Med, Oklahoma City, OK USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Rosovsky, Rachel] Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, Boston, MA 02114 USA. [Kabrhel, Christopher] Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA. RP Kabrhel, C (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Ctr Vasc Emergencies, Boston, MA 02114 USA. EM ckabrhel@partners.org OI Kabrhel, Christopher/0000-0002-8699-7176 FU Harvard Milton fund, Boston, Massachusetts FX This work was supported by a grant from the Harvard Milton fund, Boston, Massachusetts. This sponsor had no role in study design, data collection or analysis, or in the writing of the report. NR 28 TC 0 Z9 2 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 2015 VL 115 IS 5 BP 681 EP 686 DI 10.1016/j.amjcard.2014.12.025 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CD4CG UT WOS:000351029600022 PM 25586333 ER PT J AU Lawrence, LA Mulligan, JK Roach, C Pasquini, WN Soler, ZM Banglawala, SM Karnezis, TT Gudis, DA Schlosser, RJ AF Lawrence, Lauren A. Mulligan, Jennifer K. Roach, Catherine Pasquini, Whitney N. Soler, Zachary M. Banglawala, Sarfaraz M. Karnezis, Tom T. Gudis, David A. Schlosser, Rodney J. TI Superoxide dismutase reduces the inflammatory response to Aspergillus and Alternaria in human sinonasal epithelial cells derived from patients with chronic rhinosinusitis SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID EOSINOPHILIC CHRONIC RHINOSINUSITIS; NASAL POLYPS; IN-VITRO; AIRWAY EPITHELIUM; OXIDATIVE STRESS; AIRBORNE FUNGI; EXPRESSION; ASTHMA; FUMIGATUS; ANTIOXIDANTS AB Background: Aspergillus fumigatus and Alternaria alternata are ubiquitous environmental fungal allergens that can exacerbate airway inflammation and contribute to the disease process in patients with chronic rhinosinusitis (CRS). These antigens have been shown to induce human sinonasal epithelial cells (HSNECs) to promote a proinflammatory response, but what is unclear is a means by which to reduce these effects. Inhaled pathogens can induce HSNECs to produce reactive oxygen species (ROS) that trigger cytokine production. Objective: This study aimed to determine whether the free radical scavenger superoxide dismutase (SOD) could reduce HSNEC-derived inflammation, as measured by interleukin (IL)-6 and IL-8 production, in response to Aspergillus or Alternaria exposure. Methods: Sinus tissue explants were collected at the time of surgery from control patients (n = 7) and patients with CRS with nasal polyps (CRSwNP) (n = 9). HSNECs were cultured from the explants and treated with Aspergillus, Alternaria, and SOD for 24 hours. Cell supernatants and lysates were collected, and IL-6 and IL-8 concentrations were measured using enzyme-linked immunosorbent assay. Results: In control and CRSwNP HSNECs, Aspergillus and Alternaria both increased cytokine production (p < 0.05), as measured by IL-6 and IL-8 concentration. SOD treatment reduced the inflammatory response to fungal antigen exposure from CRSwNP HSNECs but not control HSNECs. In CRSwNP patients, SOD significantly decreased IL-6 and IL-8 production after Alternaria exposure and IL-8 after Aspergillus exposure (p < 0.05). Conclusions: When HSNECs from CRSwNP patients are treated with SOD concurrently with Aspergillus or Alternaria, SOD treatment decreases the fungal antigen-induced inflammatory response. The ability to attenuate inflammation induced by common fungal allergens with SOD treatment could provide a novel therapeutic or preventative approach for patients with CRS or other allergic inflammatory airway diseases. C1 [Lawrence, Lauren A.; Mulligan, Jennifer K.; Roach, Catherine; Pasquini, Whitney N.; Soler, Zachary M.; Banglawala, Sarfaraz M.; Karnezis, Tom T.; Gudis, David A.; Schlosser, Rodney J.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Mulligan, Jennifer K.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Mulligan, Jennifer K.; Schlosser, Rodney J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Lawrence, LA (reprint author), Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge,MSC-550, Charleston, SC 29425 USA. EM lawre194@gmail.com FU Department of Veterans Affairs, Veterans Health Administration, Clinical Sciences Research and Development Merit Award; CSRD [1I01CX000377-01A2]; Optinose; Intersect ENT; Flight Attendant Medical Research Institute [092401] FX This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Clinical Sciences Research and Development Merit Award, and the CSRD Grant 1I01CX000377- 01A2. This material is the result of work supported with resources and the use of facilities at the Ralph H. Johnson VA Medical Center, Charleston, South Carolina; R J Schlosser is a consultant for BrainLAB Inc. and Olympus and has been provided grant support from Optinose and Intersect ENT; none of these provided support for this investigation. Z M Soler is also consultant for BrainLAB Inc., but no support was provided for this investigation. J K Mulligan is funded by a grant from the Flight Attendant Medical Research Institute (ID, 092401), which was not affiliated with this investigation. The remaining authors have no conflicts of interest pertaining to this article NR 41 TC 1 Z9 1 U1 1 U2 2 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 EI 1945-8932 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD MAR-APR PY 2015 VL 29 IS 2 BP 89 EP 93 DI 10.2500/ajra.2015.29.4155 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA CE3HL UT WOS:000351717200007 PM 25785747 ER PT J AU Sedaghat, AR Gray, ST Caradonna, SD Caradonna, DS AF Sedaghat, Ahmad R. Gray, Stacey T. Caradonna, Scott D. Caradonna, David S. TI Clustering of chronic rhinosinusitis symptomatology reveals novel associations with objective clinical and demographic characteristics SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID SINONASAL OUTCOME TEST; ALLERGIC RHINITIS; SINUS SURGERY; PATHOGENESIS; SCORES AB Background: Chronic rhinosinusitis (CRS) is associated with varied head and neck symptomatology and quality-of-life impairments that are not necessarily correlated with each other or with objective measures of disease. Objective: To determine how clustering patterns of CRS symptoms associate with objective clinical findings. Methods: Symptom scores from 193 Sinonasal Outcomes Test-22 (SNOT-22) questionnaires, from 177 consecutive CRS patients, were analyzed by principal component analysis (PCA) to uncover fewer and physiologically understandable latent components. Univariate and multivariate regressions were made with patients' demographic characteristics, nasal polyposis, comorbid allergic rhinitis, asthma, gastro-esophageal reflux disease (GERD) or depression, and Lund-Mackay scoring of sinus computed tomography (CT) results. Results: Four principal components (PCs), heavily weighted on sleep symptoms, nasal symptoms, otologic symptoms, and emotional function symptoms, respectively, are found to primarily describe the variability in patients' SNOT-22 scores. SNOT-22 subset scores reflecting sleep, nasal, otologic, and emotional function symptoms were constructed from corresponding PCs. Only female gender associated with the total SNOT-22 score (p = 0.004), whereas only Lund-Mackay score associated with the nasal subset score (p = 0.015). Allergic rhinitis only associated with the otologic subset score (p = 0.005), whereas only asthma associated with the emotional function subset score (p = 0.027). None of the measured covariates were associated with the sleep subset score. Conclusion: Variability in SNOT-22 scores from CRS patients may be explained by the independent presence of sleep, nasal, otologic, and emotional function symptoms, with which we find novel clinical and demographic associations. These findings may represent clinical evidence for distinct pathophysiologic processes that differentially cause specific CRS symptomatology. C1 [Sedaghat, Ahmad R.; Gray, Stacey T.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Sedaghat, Ahmad R.; Caradonna, Scott D.; Caradonna, David S.] Beth Israel Deaconess Med Ctr, Div Otolaryngol, Boston, MA 02215 USA. [Sedaghat, Ahmad R.; Gray, Stacey T.; Caradonna, David S.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Sedaghat, AR (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM ahmad_sedaghat@meei.harvard.edu NR 25 TC 9 Z9 9 U1 0 U2 3 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 EI 1945-8932 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD MAR-APR PY 2015 VL 29 IS 2 BP 100 EP 105 DI 10.2500/ajra.2015.29.4140 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA CE3HL UT WOS:000351717200009 PM 25785749 ER PT J AU Miyake, MM Bleier, BS AF Miyake, Marcel Menon Bleier, Benjamin S. TI The blood-brain barrier and nasal drug delivery to the central nervous system SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID INTRAVENOUS DELIVERY; CEREBROSPINAL-FLUID; BACTERIAL-MENINGITIS; OLFACTORY PATHWAY; RAT-BRAIN; INTRANASAL; MICRODIALYSIS; TRANSPORT; CHEMOTHERAPY; FLUORESCEIN AB Background: The blood-brain barrier (BBB) is a highly efficient system that separates the central nervous system (CNS) from general circulation and promotes selective transport of molecules that are essential for brain function. However, it also limits the distribution of systemically administered therapeutics to the brain; therefore, there is a restricted number of drugs available for the treatment of brain disorders. Several drug-targeting strategies have been developed to attempt to bypass the BBB, but none has proved sufficiently effective in reaching the brain. Methods: The objective of this study is to generally review these strategies of drug administration to the CNS. Results: Noninvasive methods of drug delivery, such as chemical and biologic transport systems, do not represent a feasible platform, whereas for most drugs, it is still not possible to achieve therapeutic levels within the brain tissue after intravenous or oral administration, and the use of higher potency or more concentrated doses may cause serious toxic side effects. Direct intrathecal drug delivery through a catheter into the CNS also presents several problems. Intranasal drug delivery is a potential alternative method due to the direct transport into the cerebrospinal fluid (CSF) compartment along the olfactory pathway, but the study's conclusions are controversial. An endoscopic intranasal surgical procedure using established skull base surgery reconstruction techniques based on the use of a nasal mucosa surgical flap as the only obstacle between the nose and the subarachnoid space has appeared as a potential solution to increase the absorption of intranasal drugs to the CNS. Conclusion: Despite extensive efforts to develop new techniques to cross the BBB, none has proved sufficiently effective in reaching the brain, whereas minimizing adverse effects and the endoscopic mucosal grafting technique offers new potential promise. C1 [Miyake, Marcel Menon] Irmandade Santa Casa Misericordia Sao Paulo, Dept Otolaryngol, BR-04509020 Sao Paulo, Brazil. [Bleier, Benjamin S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Miyake, MM (reprint author), Irmandade Santa Casa Misericordia Sao Paulo, Rua Afonso Braz,525,Cj 22, BR-04509020 Sao Paulo, Brazil. EM marcelmenon@yahoo.com.br NR 68 TC 6 Z9 8 U1 5 U2 37 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 EI 1945-8932 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD MAR-APR PY 2015 VL 29 IS 2 BP 124 EP 127 DI 10.2500/ajra.2015.29.4149 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA CE3HL UT WOS:000351717200013 PM 25785753 ER PT J AU Saha, S Shaik, M Johnston, G Saha, SK Berbiglia, L Hicks, M Gernand, J Grewal, S Arora, M Wiese, D AF Saha, Sukamal Shaik, Mohammed Johnston, Gregory Saha, Supriya Kumar Berbiglia, Lindsay Hicks, Micheal Gernand, Jill Grewal, Sandeep Arora, Madan Wiese, David TI Tumor size predicts long-term survival in colon cancer: an analysis of the National Cancer Data Base SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Colon cancer; Tumor size; Prognostic significance; Staging; Overall survival ID COLORECTAL-CANCER; PROGNOSTIC-FACTORS; METASTASIS; STAGE AB BACKGROUND: American Joint Committee on Cancer uses tumor size for "T" staging of many solid tumors for its effect on prognosis. However, tumor size has not been incorporated in tumor (T), nodal status (N), metastasis (M) staging for colon cancer. Hence, the National Cancer Data Base was used to determine whether tumor size correlates with TNM staging and survival. METHODS: For the 300,386 patients, tumor size was divided into S-1 (0 to 2 cm), S-2 (>2 to 4 cm), S-3 (>4 to 6 cm), and S-4 (>6 cm). Statistical comparison was done for TNM stage, grade, and nodal status with tumor size. Kaplan-Meier survival analysis was done for each "S" stage. RESULTS: Of the 300,386 patients, 13% were classified as S-1, 39% S-2, 30% S-3 and 18% as S-4. Right colon was the most common site (48%). Tumor size positively correlated with grade, T stage, and nodal stage. Tumor size was inversely associated with survival. CONCLUSION: Tumor size is positively correlated with important prognostic factors and negatively impacted survival. (C) 2015 Elsevier Inc. All rights reserved. C1 [Saha, Sukamal; Berbiglia, Lindsay; Hicks, Micheal; Gernand, Jill] McLaren Reg Med Ctr, Dept Surg, Flint, MI 48532 USA. [Shaik, Mohammed] Michigan State Univ, Div Hematol Oncol, E Lansing, MI 48824 USA. [Johnston, Gregory] McLaren Macomb, Dept Surg, Mt Clemens, MI USA. [Saha, Supriya Kumar] Harvard Univ, Sch Med, Dept Hematol Oncol, Massachusettes Gen Hosp,Canc Ctr, Boston, MA USA. [Grewal, Sandeep; Arora, Madan] McLaren Reg Med Ctr, Dept Hematol Oncol, Flint, MI 48532 USA. [Wiese, David] McLaren Reg Med Ctr, Dept Pathol, Flint, MI 48532 USA. RP Saha, S (reprint author), McLaren Reg Med Ctr, Dept Surg, Flint, MI 48532 USA. EM ssahadr@aol.com NR 13 TC 7 Z9 7 U1 2 U2 12 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD MAR PY 2015 VL 209 IS 3 BP 570 EP 574 DI 10.1016/j.amjsurg.2014.12.008 PG 5 WC Surgery SC Surgery GA CD6FB UT WOS:000351183800027 PM 25601557 ER PT J AU Stappenbeck, CA Luterek, JA Kaysen, D Rosenthal, CF Gurrad, B Simpson, TL AF Stappenbeck, Cynthia A. Luterek, Jane A. Kaysen, Debra Rosenthal, Christina F. Gurrad, Bethann Simpson, Tracy L. TI A controlled examination of two coping skills for daily alcohol use and PTSD symptom severity among dually diagnosed individuals SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Coping behavior; Posttraumatic stress disorder; Alcohol dependence; Dual diagnosis; Cognitive restructuring; Experiential acceptance ID POSTTRAUMATIC-STRESS-DISORDER; SUBSTANCE USE DISORDERS; CONFIRMATORY FACTOR-ANALYSIS; RELAPSE PREVENTION; THOUGHT SUPPRESSION; COCAINE ABUSE; USE OUTCOMES; DEPENDENCE; THERAPY; EXPOSURE AB Investigations of targeted coping skills could help guide initial treatment decisions for individuals with co-occurring posttraumatic stress disorder (PTSD) and alcohol dependence (AD) who often endorse worse coping skills than those with AD but not PTSD. Although improvement in coping skills is associated with enhanced alcohol use outcomes, no study has evaluated the utility of teaching specific coping skills in the context of comorbid PTSD/AD. We compared the effects of teaching two coping skills (cognitive restructuring [CR] and experiential acceptance [EA]) or an attention control condition on drinking and PTSD symptoms among 78 men and women with comorbid PTSD/AD during a 5-week daily follow-up assessment. Both CR and EA skills were associated with decreased drinking compared to control, and that change in drinking over time did not significantly differ between those who received CR and EA. Individuals who received CR skills, however, consumed less alcohol on a given day than those who received EA skills. Neither CR nor EA was associated with a decrease in PTSD symptom severity. These results provide preliminary support for clinicians to prioritize CR and EA skills during initial treatment sessions when working with individuals with PTSD/AD, and offer ideas for continued investigation and intervention refinement. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Stappenbeck, Cynthia A.; Kaysen, Debra; Simpson, Tracy L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98105 USA. [Luterek, Jane A.; Rosenthal, Christina F.; Gurrad, Bethann; Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Stappenbeck, CA (reprint author), Univ Washington, Box 354944, Seattle, WA 98105 USA. EM cstappen@uw.edu FU NIH/NIAAA [R21AA17130] FX This study was supported in part by a grant from NIH/NIAAA (R21AA17130; PI: Simpson) as well as by resources from the Center of Excellence in Substance Abuse Treatment and Education (CESATE) at the VA Puget Sound Health Care System. NR 63 TC 3 Z9 3 U1 2 U2 23 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 EI 1873-622X J9 BEHAV RES THER JI Behav. Res. Ther. PD MAR PY 2015 VL 66 BP 8 EP 17 DI 10.1016/j.brat.2014.12.013 PG 10 WC Psychology, Clinical SC Psychology GA CD7CU UT WOS:000351249200002 PM 25617814 ER PT J AU Iverson, KM King, MW Cunningham, KC Resick, PA AF Iverson, Katherine. M. King, Matthew W. Cunningham, Katherine C. Resick, Patricia A. TI Rape survivors' trauma-related beliefs before and after Cognitive processing therapy: Associations with PTSD and depression symptoms SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Cognitive distortions; Cognitive-behavioral therapy; Posttraumatic stress disorder; Depression; Mixed-methods ID POSTTRAUMATIC-STRESS-DISORDER; 5-YEAR FOLLOW-UP; INVENTORY; EXPOSURE; VICTIMS AB This study examined whether cognitive distortions (i.e., assimilated and overaccommodated thoughts) and realistic (i.e., accommodated) thoughts assessed from impact statements written 5-10 years after completing cognitive processing therapy (CPT) accurately predicted posttreatment maintenance or decline in treatment gains during the same period. The sample included 50 women diagnosed with posttraumatic stress disorder (PTSD) secondary to rape who participated in a randomized clinical trial of CPT for PTSD. Cognitions were assessed via coding and analyses of participants' written impact statements at three time points: beginning of treatment, end of treatment, and at 5-10 years follow-up. Primary mental health outcomes were symptoms of PTSD (Clinician-Administered PTSD Scale) and depression (Beck Depression Inventory). Changes in trauma-related beliefs between the end of treatment and long-term follow-up were associated with concomitant changes in PTSD and depression symptoms (effect sizes ranging from r = .35-.54). Declines in accommodated thinking and increases in overaccommodated thinking were associated with elevations in symptomatology. Improvement in accommodated thinking and declines in overaccommodated thinking were associated with lower PTSD and depression symptoms during this same time period. Findings provided support for the role of changes in accommodated and overaccommodated thinking being associated with level of PTSD and depression many years after participating in CPT. Published by Elsevier Ltd. C1 [Iverson, Katherine. M.; King, Matthew W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Iverson, Katherine. M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Cunningham, Katherine C.] Univ Tulsa, Dept Psychol, Tulsa, OK 74104 USA. [Resick, Patricia A.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. RP Iverson, KM (reprint author), WHSD 116B 3 VA Boston Healthcare Syst, 150 South Huntington Ave,116B 3, Boston, MA 02130 USA. EM Katherine.Iverson@va.gov FU National Institute of Mental Health [NIH-1 R01-MH51509]; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) Service as part of her Career Development Award [CDA 10-029]; Presidential Early Career Award for Scientists and Engineers [USA 14-275] FX This research was funded by a grant from the National Institute of Mental Health (NIH-1 R01-MH51509) awarded to Patricia A. Resick. Dr. Iverson's contribution to this manuscript was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) Service as part of her Career Development Award (CDA 10-029) and her Presidential Early Career Award for Scientists and Engineers (USA 14-275). The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 25 TC 4 Z9 4 U1 3 U2 32 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 EI 1873-622X J9 BEHAV RES THER JI Behav. Res. Ther. PD MAR PY 2015 VL 66 BP 49 EP 55 DI 10.1016/j.brat.2015.01.002 PG 7 WC Psychology, Clinical SC Psychology GA CD7CU UT WOS:000351249200006 PM 25698164 ER PT J AU Loggia, ML Chonde, DB Akeju, O Arabasz, G Catana, C Edwards, RR Hill, E Hsu, S Izquierdo-Garcia, D Ji, RR Riley, M Wasan, AD Zurcher, NR Albrecht, DS Vangel, MG Rosen, BR Napadow, V Hooker, JM AF Loggia, Marco L. Chonde, Daniel B. Akeju, Oluwaseun Arabasz, Grae Catana, Ciprian Edwards, Robert R. Hill, Elena Hsu, Shirley Izquierdo-Garcia, David Ji, Ru-Rong Riley, Misha Wasan, Ajay D. Zuercher, Nicole R. Albrecht, Daniel S. Vangel, Mark G. Rosen, Bruce R. Napadow, Vitaly Hooker, Jacob M. TI Evidence for brain glial activation in chronic pain patients SO BRAIN LA English DT Article DE chronic pain; C-11-PBR28; translocator protein (18kDa); TSPO; neuroinflammation; glia ID PROTEIN 18 KDA; PERIPHERAL BENZODIAZEPINE-RECEPTOR; POSITRON-EMISSION-TOMOGRAPHY; LOW-DOSE NALTREXONE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; IN-VITRO EVIDENCE; TRANSLOCATOR PROTEIN; NEUROPATHIC PAIN; SPINAL-CORD; NERVE INJURY AB Although substantial evidence has established that microglia and astrocytes play a key role in the establishment and maintenance of persistent pain in animal models, the role of glial cells in human pain disorders remains unknown. Here, using the novel technology of integrated positron emission tomography-magnetic resonance imaging and the recently developed radioligand C-11-PBR28, we show increased brain levels of the translocator protein (TSPO), a marker of glial activation, in patients with chronic low back pain. As the Ala147Thr polymorphism in the TSPO gene affects binding affinity for C-11-PBR28, nine patient-control pairs were identified from a larger sample of subjects screened and genotyped, and compared in a matched-pairs design, in which each patient was matched to a TSPO polymorphism-, age-and sex-matched control subject (seven Ala/Ala and two Ala/Thr, five males and four females in each group; median age difference: 1 year; age range: 29-63 for patients and 28-65 for controls). Standardized uptake values normalized to whole brain were significantly higher in patients than controls in multiple brain regions, including thalamus and the putative somatosensory representations of the lumbar spine and leg. The thalamic levels of TSPO were negatively correlated with clinical pain and circulating levels of the proinflammatory citokine interleukin-6, suggesting that TSPO expression exerts pain-protective/anti-inflammatory effects in humans, as predicted by animal studies. Given the putative role of activated glia in the establishment and or maintenance of persistent pain, the present findings offer clinical implications that may serve to guide future studies of the pathophysiology and management of a variety of persistent pain conditions. C1 [Loggia, Marco L.; Chonde, Daniel B.; Arabasz, Grae; Catana, Ciprian; Hsu, Shirley; Izquierdo-Garcia, David; Riley, Misha; Zuercher, Nicole R.; Albrecht, Daniel S.; Vangel, Mark G.; Rosen, Bruce R.; Napadow, Vitaly; Hooker, Jacob M.] Harvard Univ, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. [Loggia, Marco L.; Edwards, Robert R.; Ji, Ru-Rong; Wasan, Ajay D.; Napadow, Vitaly] Massachusetts Gen Hosp, Dept Anesthesiol Perioperat & Pain Med, Brigham & Womens Hosp, Sch Med, Boston, MA 02155 USA. [Akeju, Oluwaseun] MGH HMS, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Edwards, Robert R.; Wasan, Ajay D.] HMS, Brigham & Womens Hosp, Dept Psychiat, Medford, MA 02155 USA. [Hill, Elena] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Ji, Ru-Rong] Duke Univ, Med Ctr, Dept Anesthesiol, Durham, NC 27705 USA. [Ji, Ru-Rong] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27705 USA. [Wasan, Ajay D.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15206 USA. [Wasan, Ajay D.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15206 USA. [Rosen, Bruce R.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Napadow, Vitaly] Kyung Hee Univ, Dept Biomed Engn, Seoul 130872, South Korea. RP Loggia, ML (reprint author), Massachusetts Gen Hosp, Bldg 149,Suite 2301, Charlestown, MA 02129 USA. EM marco@nmr.mgh.harvard.edu OI Ji, Ru-Rong/0000-0002-9355-3688 FU Harvard Catalyst Advanced Imaging Pilot Grant; National Centre for Advancing Translational Science [1R21NS087472-01A1, 1UL1TR001102-01, 8UL1TR000170-05]; National Centre for Research Resources [1UL1RR025758-04]; Harvard Clinical and Translational Science Centre; Harvard University; academic healthcare centres FX This project was supported by Harvard Catalyst Advanced Imaging Pilot Grant (J.M.H.), 1R21NS087472-01A1 (M.L.L.) 1UL1TR001102-01, 8UL1TR000170-05, from the National Centre for Advancing Translational Science, and 1UL1RR025758-04 from the National Centre for Research Resources, Harvard Clinical and Translational Science Centre, and financial contributions from Harvard University and its affiliated academic healthcare centres. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centres, or the National Institutes of Health. The authors have no conflicts of interest or competing financial interests to declare. NR 95 TC 60 Z9 62 U1 10 U2 34 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD MAR 1 PY 2015 VL 138 BP 604 EP 615 DI 10.1093/brain/awu377 PN 3 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CE0QY UT WOS:000351510700018 PM 25582579 ER PT J AU Chebib, I Hornicek, FJ Nielsen, GP Deshpande, V AF Chebib, Ivan Hornicek, Francis J. Nielsen, G. Petur Deshpande, Vikram TI Cytomorphologic Features That Distinguish Schwannoma From Other Low-Grade Spindle Cell Lesions SO CANCER CYTOPATHOLOGY LA English DT Article DE fine-needle aspiration biopsy; schwannoma; spindle cell neoplasm; low grade; gastrointestinal stromal tumor; fibromatosis ID FINE-NEEDLE-ASPIRATION; GASTROINTESTINAL STROMAL TUMOR; SOFT-TISSUE TUMORS; NERVE SHEATH TUMOR; CYTOLOGIC FEATURES; BIOPSY DIAGNOSIS; CORE BIOPSY; SARCOMAS; IMMUNOCYTOCHEMISTRY; EXPERIENCE AB BACKGROUNDFine-needle aspiration biopsy of spindled mesenchymal lesions, including schwannomas, are challenging because of overlapping cytomorphological features. The objective of the current study was to identify key diagnostic cytological criteria for the diagnosis of schwannoma and to distinguish it from its common mimics. METHODSA total of 58 schwannomas were evaluated and compared with 98 benign and low-grade spindle cell lesions, including 17 gastrointestinal stromal tumors and 20 fibromatosis cases. Biopsy confirmation was available for all cases. The authors semiquantitatively evaluated cellularity, quality of stroma (fibrous and fibrillar), the presence of single cells with bipolar cytoplasmic processes, and marked nuclear pleomorphism (in the absence of other features of malignancy). Nuclear features evaluated included fishhook-type nuclei, intranuclear inclusions, chromatin pattern, and nucleoli. RESULTSSchwannomas demonstrated cohesive tissue fragments with fibrillary and occasionally fibrous stroma. The presence of intranuclear inclusions and marked nuclear pleomorphism and the absence of single cells with bipolar cytoplasmic processes emerged as statistically significant differences between the schwannoma and the nonschwannoma groups. When 5 criteria were present (high numbers of clusters, few to no single cells, fibrillary stroma, nuclei with pointed tips, and anisonucleosis) the sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of schwannoma were 22%, 97%, 81%, and 68%, respectively. CONCLUSIONSCohesive tissue fragments with fibrillary/fibrous stroma, intranuclear inclusions, marked nuclear pleomorphism, and the absence of spindled cells with bipolar cytoplasmic processes are strongly suggestive of schwannoma and assist in excluding potential mimics. Cancer (Cancer Cytopathol) 2015. (c) 2015 American Cancer Society. Cancer (Cancer Cytopathol) 2015;123:171-179. (c) 2014 American Cancer Society. The objective of the current study was to identify key diagnostic cytological criteria for the diagnosis of schwannoma and to distinguish it from its common mimics. Cohesive tissue fragments with fibrillary/fibrous stroma, intranuclear inclusions, marked nuclear pleomorphism, and the absence of spindled cells with bipolar cytoplasmic processes are strongly suggestive of schwannoma and assist in excluding other low-grade spindle cell tumors from the diagnosis. C1 [Chebib, Ivan; Nielsen, G. Petur; Deshpande, Vikram] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Hornicek, Francis J.] Harvard Univ, Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Dept Orthopaed Surg,Med Sch, Boston, MA 02114 USA. RP Chebib, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, WRN2,55 Fruit St, Boston, MA 02114 USA. EM ichebib@partners.org NR 39 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD MAR PY 2015 VL 123 IS 3 BP 171 EP 179 DI 10.1002/cncy.21506 PG 9 WC Oncology; Pathology SC Oncology; Pathology GA CD7ZN UT WOS:000351315000006 PM 25641870 ER PT J AU Leonard, MK Novak, M McCorkle, JR Yang, XWH Belkin, A Kaetzel, DM AF Leonard, M. Katie Novak, Marian McCorkle, Joseph R. Yang, Xiuwei H. Belkin, Alexey Kaetzel, David M. TI The metastasis suppressor NME1 suppresses melanoma cell motility through alterations in integrin repertoire and focal adhesion dynamics SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Leonard, M. Katie; Belkin, Alexey; Kaetzel, David M.] Univ Maryland, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. [Leonard, M. Katie; Kaetzel, David M.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Novak, Marian] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. [McCorkle, Joseph R.] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA. [Yang, Xiuwei H.] Univ Kentucky, Coll Med, Dept Mol & Biomed Pharmacol, Lexington, KY 40536 USA. [Belkin, Alexey] Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 EI 1573-7276 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD MAR PY 2015 VL 32 IS 3 MA 69 BP 213 EP 214 PG 2 WC Oncology SC Oncology GA CE1VX UT WOS:000351601900099 ER PT J AU Afnan, J Snuderl, M Small, J AF Afnan, Jalil Snuderl, Matija Small, Juan TI Intracranial, intradural aneurysmal bone cyst SO CLINICAL IMAGING LA English DT Article DE Aneurysmal bone cyst; Intracraniat; Intradural; Imaging; Pathology AB Aneurysmal bone cysts (ABCs) are benign, expansile, blood-filled, osteolytic lesions with internal septations that may be intraosseous or extraosseous. The cysts may cause local mass effect, and changes in the regional vascular supply necessitating intervention. A case of an intracranial, intradural ABC in a young male patient with progressively severe headaches is presented. This is only the third recorded intradural case, the majority of these rare lesions being extracranial and only a minute fraction intracranial. (C) 2015 Elsevier Inc. All rights reserved. C1 [Afnan, Jalil] Lahey Hosp & Med Ctr, Dept Radiol, Burlington, MA 01803 USA. [Snuderl, Matija] NYU, Langone Med Ctr, Dept Pathol, New York, NY 10003 USA. [Small, Juan] Lahey Hosp & Med Ctr, Dept Neuroradiol, Burlington, MA 01803 USA. [Small, Juan] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. RP Small, J (reprint author), Lahey Hosp & Med Ctr, Dept Neuroradiol, 41 Mall Rd, Burlington, MA 01803 USA. EM Juan.E.Small@Lahey.org OI Snuderl, Matija/0000-0003-0752-0917 NR 16 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-7071 EI 1873-4499 J9 CLIN IMAG JI Clin. Imaging PD MAR-APR PY 2015 VL 39 IS 2 BP 297 EP 299 DI 10.1016/j.clinimag.2014.11.004 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CE0HJ UT WOS:000351484800024 PM 25482352 ER PT J AU Higgins, JM AF Higgins, John M. TI Red Blood Cell Population Dynamics SO CLINICS IN LABORATORY MEDICINE LA English DT Article DE Red blood cell population dynamics; Single-RBC measurements; Mathematical modeling; RBC life span; RBC turnover; Diagnostic applications; Predictive medicine; Personalized medicine ID RETICULOCYTE; VESICULATION; ERYTHROCYTES; SURVIVAL; ANEMIA; VOLUME AB Hematology analyzers provide a static snapshot of the circulating population of red blood cells (RBCs). The RBC population is rapidly changing, with more than 2 million RBCs turning over every second in the typical healthy adult. The static snapshot provided by the complete blood count does not capture many of the dynamic aspects of this population, such as the rate of RBC maturation and the rate of RBC turnover. By integrating basic science with hematology analyzer measurements, it is possible to estimate the rates of these dynamic processes, yielding new insights into human physiology, with potential diagnostic application. C1 [Higgins, John M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Higgins, John M.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Higgins, John M.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Higgins, JM (reprint author), Massachusetts Gen Hosp, Dept Pathol, 185 Cambridge St, Boston, MA 02114 USA. EM higgins.john@mgh.harvard.edu FU NIH Director's New Innovator Award [DP2DK098087] FX The author was supported by an NIH Director's New Innovator Award DP2DK098087. NR 20 TC 2 Z9 2 U1 1 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-2712 EI 1557-9832 J9 CLIN LAB MED JI Clin. Lab. Med. PD MAR PY 2015 VL 35 IS 1 BP 43 EP + DI 10.1016/j.cll.2014.10.002 PG 16 WC Medical Laboratory Technology SC Medical Laboratory Technology GA CD2YH UT WOS:000350944400005 PM 25676371 ER PT J AU Keller, JB Hedden, T Thompson, TW Anteraper, SA Gabrieli, JDE Whitfield-Gabrieli, S AF Keller, Joseph B. Hedden, Trey Thompson, Todd W. Anteraper, Sheeba A. Gabrieli, John D. E. Whitfield-Gabrieli, Susan TI Resting-state anticorrelations between medial and lateral prefrontal cortex: Association with working memory, aging, and individual differences SO CORTEX LA English DT Article DE Default mode network; Working memory; Resting-state fMRI; Aging; Functional connectivity ID DEFAULT-MODE NETWORK; FUNCTIONAL CONNECTIVITY MRI; ANTI-CORRELATED NETWORKS; GLOBAL SIGNAL REGRESSION; WHITE-MATTER INTEGRITY; HUMAN BRAIN; COGNITIVE DECLINE; SENSORY STIMULATION; NOISE CORRECTION; SUBJECT MOTION AB We examined how variation in working memory (WM) capacity due to aging or individual differences among young adults is associated with intrinsic or resting-state anticorrelations, particularly between (1) the medial prefrontal cortex (MPFC), a component of the default-mode network (DMN) that typically decreases in activation during external, attention-demanding tasks, and (2) the dorsolateral prefrontal cortex DLPFC, a component of the fronto-parietal control network that supports executive functions and WM and typically increases in activation during attention-demanding tasks. We compared the magnitudes of MPFC-DLPFC anticorrelations between healthy younger and older participants (Experiment 1) and related the magnitudes of these anticorrelations to individual differences on two behavioral measures of VIM capacity in two independent groups of young adults (Experiments 1 and 2). Relative to younger adults, older adults exhibited reductions in WM capacity and in MPFC-DLPFC anticorrelations. Within younger adults, greater MPFC-DLPFC anticorrelation at rest correlated with greater VIM capacity. These findings show that variation in MPFC-DLPFC anticorrelations, whether related to aging or to individual differences, may reflect an intrinsic functional brain architecture supportive of WM capacity. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Keller, Joseph B.; Thompson, Todd W.; Anteraper, Sheeba A.; Gabrieli, John D. E.; Whitfield-Gabrieli, Susan] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Keller, Joseph B.; Thompson, Todd W.; Anteraper, Sheeba A.; Gabrieli, John D. E.; Whitfield-Gabrieli, Susan] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Gabrieli, John D. E.] Inst Med Engn & Sci, Cambridge, MA USA. [Hedden, Trey] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Hedden, Trey] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Keller, JB (reprint author), MIT, Dept Brain & Cognit Sci, 43 Vassar St,4033A, Cambridge, MA 02139 USA. EM jkeller1@mit.edu FU NIH/NIA [R21 AG030770]; NIH [T32 GM007484]; Barbara J. Weedon Fund Fellowship at MIT; [K01 AG040197] FX We thank Nina Wickens for her help in recruiting and testing participants, and the staff of the Martinos Imaging Center at the McGovern Institute at MIT for help in neuroimaging. This study was supported by NIH/NIA grant R21 AG030770. Funding support for J.B.K was provided by NIH grant T32 GM007484 and the Barbara J. Weedon Fund Fellowship at MIT; support for T.H. was provided by grant K01 AG040197. NR 69 TC 20 Z9 21 U1 3 U2 14 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 EI 1973-8102 J9 CORTEX JI Cortex PD MAR PY 2015 VL 64 BP 271 EP 280 DI 10.1016/j.cortex.2014.12.001 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CD7CM UT WOS:000351248400025 PM 25562175 ER PT J AU Hermayer, KL Loftley, AS Reddy, S Narla, SN Epps, NA Zhu, YS AF Hermayer, Kathie L. Loftley, Aundrea S. Reddy, Sumana Narla, Satya Nandana Epps, Nina A. Zhu, Yusheng TI Challenges of Inpatient Blood Glucose Monitoring: Standards, Methods, and Devices to Measure Blood Glucose SO CURRENT DIABETES REPORTS LA English DT Article DE Glucose; Meter; Point of care; Hyperglycemia; Hypoglycemia; Hospital; Arterial; Venous; Capillary; i-Stat; HemoCue; YSI; Critical illness; Calibration; Continuous glucose monitoring; Maltose; Wired; Wireless; FDA; CLIA ID INTENSIVE INSULIN THERAPY; CRITICALLY-ILL PATIENTS; HEMATOCRIT; CARE; MANAGEMENT; ACCURACY; METERS; HYPERGLYCEMIA; CAPILLARY; ARTERIAL AB Glucose control in the hospital setting is very important. There is a high incidence of hyperglycemia, hypoglycemia, and glycemic variability in hospitalized patients. Safe insulin delivery and glucose control is dependent on reliable glucose meters and monitoring systems in the hospital. Different glucose monitoring systems use arterial, venous, central venous, and capillary blood samples. It is important for clinicians to be aware that there are limitations of specific point-of-care (POC) glucose meters and that situations exist whereby POC glucose meters as the sole measurement device should be avoided. POC meter devices are not approved by the Food and Drug Administration for use in critical care, although POC meter devices are commonly used in critical care settings and elsewhere. This review focuses on glucose assay principles, instrument technology, influences on glucose measurement, standards for glucose measurement, and an evaluation of different methods to measure blood glucose in the hospital setting. C1 [Hermayer, Kathie L.; Loftley, Aundrea S.; Reddy, Sumana] Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. [Hermayer, Kathie L.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Narla, Satya Nandana; Zhu, Yusheng] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Epps, Nina A.] Med Univ S Carolina, Lab Serv Point Care Testing Qual & Safety, Charleston, SC 29425 USA. RP Hermayer, KL (reprint author), Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, 96 Jonathan Lucas St,MSC 624, Charleston, SC 29425 USA. EM hermayer@musc.edu; easona@musc.edu; reddysu@musc.edu; narlas@musc.edu; eppsn@musc.edu; zhuyu@musc.edu NR 38 TC 2 Z9 2 U1 3 U2 22 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 EI 1539-0829 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD MAR PY 2015 VL 15 IS 3 AR 10 DI 10.1007/s11892-015-0582-9 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CD6WZ UT WOS:000351232400001 PM 25644818 ER PT J AU Sim, DA Keane, PA Tufail, A Egan, CA Aiello, LP Silva, PS AF Sim, Dawn A. Keane, Pearse A. Tufail, Adnan Egan, Catherine A. Aiello, Lloyd Paul Silva, Paolo S. TI Automated Retinal Image Analysis for Diabetic Retinopathy in Telemedicine SO CURRENT DIABETES REPORTS LA English DT Article DE Automated retinal image analysis; Telemedicine; Diabetes mellitus; Diabetic retinopathy ID SIGNIFICANT MACULAR EDEMA; COLOR FUNDUS PHOTOGRAPHS; MICROANEURYSM TURNOVER; SCREENING-PROGRAM; UNITED-STATES; RED LESIONS; EYE CARE; DIAGNOSIS; PREVALENCE; SEVERITY AB There will be an estimated 552 million persons with diabetes globally by the year 2030. Over half of these individuals will develop diabetic retinopathy, representing a nearly insurmountable burden for providing diabetes eye care. Telemedicine programmes have the capability to distribute quality eye care to virtually any location and address the lack of access to ophthalmic services. In most programmes, there is currently a heavy reliance on specially trained retinal image graders, a resource in short supply worldwide. These factors necessitate an image grading automation process to increase the speed of retinal image evaluation while maintaining accuracy and cost effectiveness. Several automatic retinal image analysis systems designed for use in telemedicine have recently become commercially available. Such systems have the potential to substantially improve the manner by which diabetes eye care is delivered by providing automated real-time evaluation to expedite diagnosis and referral if required. Furthermore, integration with electronic medical records may allow a more accurate prognostication for individual patients and may provide predictive modelling of medical risk factors based on broad population data. C1 [Sim, Dawn A.; Aiello, Lloyd Paul; Silva, Paolo S.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. [Sim, Dawn A.; Aiello, Lloyd Paul; Silva, Paolo S.] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Sim, Dawn A.; Keane, Pearse A.; Tufail, Adnan; Egan, Catherine A.] Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr Ophthalmol, London, England. [Sim, Dawn A.; Keane, Pearse A.; Tufail, Adnan] UCL, Inst Ophthalmol, London, England. [Silva, Paolo S.] Univ Philippines, Natl Inst Hlth, Philippine Eye Res Inst, Teleophthalmol & Image Reading Ctr, Manila, Philippines. RP Silva, PS (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, One Joslin Pl, Boston, MA 02215 USA. EM PaoloAntonio.Silva@joslin.havard.edu FU Fight for Sight, UK [1987]; Moorfields Eye Hospital; National Institute for Health Research (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust; UCL Institute of Ophthalmology FX The research was supported by a grant from Fight for Sight, UK (Grant number 1987), The Special Trustees of Moorfields Eye Hospital and the National Institute for Health Research (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology. NR 74 TC 7 Z9 7 U1 1 U2 15 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 EI 1539-0829 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD MAR PY 2015 VL 15 IS 3 AR 14 DI 10.1007/s11892-015-0577-6 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CD6WZ UT WOS:000351232400006 PM 25697773 ER PT J AU Psaros, C Remmert, JE Bangsberg, DR Safren, SA Smit, JA AF Psaros, Christina Remmert, Jocelyn E. Bangsberg, David R. Safren, Steven A. Smit, Jennifer A. TI Adherence to HIV Care After Pregnancy Among Women in Sub-Saharan Africa: Falling Off the Cliff of the Treatment Cascade SO CURRENT HIV/AIDS REPORTS LA English DT Editorial Material ID TO-CHILD TRANSMISSION; IMMUNODEFICIENCY-VIRUS TRANSMISSION; FOLLOW-UP; SOUTH-AFRICA; ANTIRETROVIRAL THERAPY; PMTCT PROGRAM; RURAL MALAWI; SCALING-UP; PREVENTION; JOHANNESBURG AB Increased access to testing and treatment means HIV can be managed as a chronic illness, though successful management requires continued engagement with the health care system. Most of the global HIV burden is in sub-Saharan Africa where rates of new infections are consistently higher in women versus men. Pregnancy is often the point at which an HIV diagnosis is made. While preventing mother to child transmission (PMTCT) interventions significantly reduce the rate of vertical transmission of HIV, women must administer ARVs to their infants, adhere to breastfeeding recommendations, and test their infants for HIV after childbirth. Some women will be expected to remain on the ARVs initiated during pregnancy, while others are expected to engage in routine testing so treatment can be reinitiated when appropriate. The postpartum period presents many barriers to sustained treatment adherence and engagement in care. While some studies have examined adherence to postpartum PMTCT guidelines, few have focused on continued engagement in care by the mother, and very few examine adherence beyond the 6-week postpartum visit. Here, we attempt to identify gaps in the research literature and make recommendations on how to address barriers to ongoing postpartum HIV care. C1 [Psaros, Christina; Remmert, Jocelyn E.; Bangsberg, David R.; Safren, Steven A.] Massachusetts Gen Hosp, Boston, MA 02140 USA. [Psaros, Christina; Bangsberg, David R.; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. [Bangsberg, David R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Smit, Jennifer A.] Univ Witwatersrand, Fac Hlth Sci, Dept Obstet & Gynaecol, Maternal Adolescent & Child Hlth Res, Durban, South Africa. [Smit, Jennifer A.] Univ KwaZulu Natal, Fac Hlth Sci, Sch Pharm & Pharmacol, Durban, South Africa. RP Psaros, C (reprint author), Massachusetts Gen Hosp, 1 Bowdoin Sq,7th Floor, Boston, MA 02140 USA. EM cpsaros@mgh.harvard.edu FU NIMH NIH HHS [K23 MH096651, K24 MH094214, K24 MH087227] NR 45 TC 9 Z9 9 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1548-3568 EI 1548-3576 J9 CURR HIV-AIDS REP JI Curr. Hiv/Aids Rep. PD MAR PY 2015 VL 12 IS 1 BP 1 EP 5 DI 10.1007/s11904-014-0252-6 PG 5 WC Infectious Diseases SC Infectious Diseases GA CD7XD UT WOS:000351307700001 PM 25620530 ER PT J AU Chahroudi, A Silvestri, G Lichterfeld, M AF Chahroudi, Ann Silvestri, Guido Lichterfeld, Mathias TI T Memory Stem Cells and HIV: a Long-Term Relationship SO CURRENT HIV/AIDS REPORTS LA English DT Article DE HIV; SIV; Memory T cell; T memory stem cell; HIV-1 reservoir; Persistence; Central memory; Effector memory; Stem cell; beta-Catenin ID SIMIAN-IMMUNODEFICIENCY-VIRUS; NATURAL SIV HOSTS; LENTIVIRAL INFECTIONS; PROGENITOR CELLS; WNT PATHWAY; IN-VIVO; EFFECTOR; RESERVOIR; DISEASE; TRANSMISSION AB In analogy to many tissues in which mature, terminally differentiated cells are continuously replenished by the progeny of less differentiated, long-lasting stem cells, it has been suspected that memory T lymphocytes might contain small numbers of stem cell-like cells. However, only recently have such cells been physically identified and isolated from humans, mice, and nonhuman primates. These cells, termed "T memory stem cells" (T-SCM), represent approximately 2-4% of all circulating T lymphocytes, seem to be extremely durable, and can rapidly differentiate into more mature central memory, effector memory, and effector T cells, while maintaining their own pool size through homeostatic self-renewal. Although it is becoming increasingly evident that that these cells have critical roles for T cell homeostasis and maintaining life-long cellular immunity against microbial pathogens during physiological conditions, they also seem intrinsically involved in many key aspects of HIV/SIV disease pathogenesis. Current data suggest that CD4+T-SCM cells represent a core element of the HIV-1 reservoir in patients treated with suppressive antiretroviral therapy (ART) and that relative resistance of CD4+ T-SCM cells to SIV represents a distinguishing feature of non-pathogenic SIV infection in natural hosts. This article summarizes recent studies investigating the role of T-SCM in HIV/SIV infection. C1 [Chahroudi, Ann] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA. [Chahroudi, Ann; Silvestri, Guido] Yerkes Natl Primate Res Ctr, Atlanta, GA USA. [Lichterfeld, Mathias] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Chahroudi, A (reprint author), Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA. EM ann.m.chahroudi@emory.edu FU American Foundation for AIDS Research [108905-56-RGRL, 108302-51-RGRL]; NICHD Child Health Research Career Development Award [K12 HD072245]; Doris Duke Charitable Foundation [2009034]; NIH grant [AI098487, AI106468, R37AI066998] FX AC is supported by the American Foundation for AIDS Research (grant 108905-56-RGRL) and by an NICHD Child Health Research Career Development Award (K12 HD072245). ML is supported by the American Foundation for AIDS Research (grant 108302-51-RGRL), by the Doris Duke Charitable Foundation (grant 2009034), and by NIH grants AI098487 and AI106468. GS is supported by NIH grant R37AI066998. NR 62 TC 6 Z9 6 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1548-3568 EI 1548-3576 J9 CURR HIV-AIDS REP JI Curr. Hiv/Aids Rep. PD MAR PY 2015 VL 12 IS 1 BP 33 EP 40 DI 10.1007/s11904-014-0246-4 PG 8 WC Infectious Diseases SC Infectious Diseases GA CD7XD UT WOS:000351307700005 PM 25578055 ER PT J AU Gogela, NA Lin, MV Wisocky, JL Chung, RT AF Gogela, Neliswa A. Lin, Ming V. Wisocky, Jessica L. Chung, Raymond T. TI Enhancing Our Understanding of Current Therapies for Hepatitis C Virus (HCV) SO CURRENT HIV/AIDS REPORTS LA English DT Article DE Direct-acting antivirals (DAAs); Protease inhibitors; NS5A inhibitors; NS5B polymerase inhibitors; HCV/HIV co-infection ID GENOTYPE 1 INFECTION; TREATMENT-NAIVE PATIENTS; SUSTAINED VIROLOGICAL RESPONSE; PEGYLATED INTERFERON; RANDOMIZED-TRIAL; VIRAL-HEPATITIS; NATURAL-HISTORY; PLUS RIBAVIRIN; UNITED-STATES; LIFE-CYCLE AB Great progress has been made in understanding the HCV genome and its molecular virology. This understanding has culminated in the development of direct-acting antiviral (DAA) agents targeting HCV viral proteins. Telaprevir (TVR) and boceprevir (BOC) were the first DAAs introduced for treatment of genotype 1 HCV in 2011; when used in combination with pegylated interferon (pegIFN) and ribavirin (RBV), these protease inhibitors improved efficacy in patients with chronic HCV infection compared to the traditional dual therapy. However, this combination was associated with adverse events that often led to early termination of therapy. In late 2013, the FDA approved a second wave of DAAs, sofosbuvir (SOF) and simeprevir (SMV). The use of SOF with SMV opened the door for IFN-free combination regimens. This combination was highly efficacious and well tolerated in patients with HCV genotype 1. Sofosbuvir and ledipasvir (LDV) fixed-dose oral combination (FDC) therapy, and paritaprevir/ritonavir, ombitasvir and dasabuvir +/- RBV were recently approved, elevating sustained virologic response (SVR) rates to over 95%. We are anticipating the approval of additional IFN-free regimens with comparable efficacy and tolerability but with the addition of pangenotypic coverage, fewer drug-drug interactions, and a high barrier to resistance. This review will summarize current management for chronic HCV infection. C1 [Gogela, Neliswa A.; Lin, Ming V.; Wisocky, Jessica L.; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Ctr Liver, Boston, MA 02114 USA. [Gogela, Neliswa A.; Lin, Ming V.; Wisocky, Jessica L.; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Div, Boston, MA 02114 USA. [Lin, Ming V.; Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lin, Ming V.] Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Ctr Liver, 55 Fruit St, Boston, MA 02114 USA. EM Chung.Raymond@mgh.harvard.edu FU Gilead; AbbVie; MassBiologics; BMS (clinical trials) FX Raymond T. Chung reports grant support from Gilead, AbbVie, MassBiologics, and BMS (clinical trials). NR 77 TC 11 Z9 11 U1 0 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1548-3568 EI 1548-3576 J9 CURR HIV-AIDS REP JI Curr. Hiv/Aids Rep. PD MAR PY 2015 VL 12 IS 1 BP 68 EP 78 DI 10.1007/s11904-014-0243-7 PG 11 WC Infectious Diseases SC Infectious Diseases GA CD7XD UT WOS:000351307700008 PM 25761432 ER PT J AU Chen, HM Fujita, M AF Chen, Hui-min Fujita, Mayumi TI IL-37: A new player in immune tolerance SO CYTOKINE LA English DT Editorial Material ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; ADAPTIVE IMMUNITY; DENDRITIC CELLS; INTERLEUKIN 37; EXPRESSION; INNATE; DISEASE; PROTECTS; OBESITY; MEMBERS C1 [Chen, Hui-min; Fujita, Mayumi] Univ Colorado, Dept Dermatol, Aurora, CO 80045 USA. [Fujita, Mayumi] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Fujita, M (reprint author), Univ Colorado, Dept Dermatol, Anschutz Med Campus, Aurora, CO 80045 USA. EM Mayumi.Fujita@ucdenver.edu FU NIAMS NIH HHS [P30AR057212] NR 27 TC 7 Z9 8 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD MAR PY 2015 VL 72 IS 1 BP 113 EP 114 DI 10.1016/j.cyto.2014.11.025 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA CD8CI UT WOS:000351322400017 PM 25592113 ER PT J AU Paciorkowski, AR McDaniel, SS Jansen, LA Tully, H Tuttle, E Ghoneim, DH Tupal, S Gunter, SA Vasta, V Zhang, Q Tran, T Liu, YB Ozelius, LJ Brashear, A Sweadner, KJ Dobyns, WB Hahn, S AF Paciorkowski, Alex R. McDaniel, Sharon S. Jansen, Laura A. Tully, Hannah Tuttle, Emily Ghoneim, Dalia H. Tupal, Srinivasan Gunter, Sonya A. Vasta, Valeria Zhang, Qing Thao Tran Liu, Yi B. Ozelius, Laurie J. Brashear, Allison Sweadner, Kathleen J. Dobyns, William B. Hahn, Sihoun TI Novel mutations in ATP1A3 associated with catastrophic early life epilepsy, episodic prolonged apnea, and postnatal microcephaly SO EPILEPSIA LA English DT Article DE ATP1A3; Early life epilepsy; Apnea; Postnatal microcephaly; Na; K-ATPase; Next-generation sequencing ID ONSET DYSTONIA-PARKINSONISM; DE-NOVO MUTATIONS; RAPID-ONSET; ALTERNATING HEMIPLEGIA; NA/K-ATPASE; CHILDHOOD; GENE; INTERNEURONS; NA,K-ATPASE; SPECTRUM AB Objective: Mutations of ATP1A3 have been associated with rapid onset dystonia-parkinsonism and more recently with alternating hemiplegia of childhood. Here we report onechild with catastrophic early life epilepsy and shortened survival, and another with epilepsy, episodic prolonged apnea, postnatal microcephaly, and severe developmental disability. Novel heterozygous mutations (p.Gly358Val and p.Ile363Asn) were identified in ATP1A3in these children. Methods: Subjects underwent next-generation sequencing under a research protocol. Clinical data were collected retrospectively. The biochemical effects of the mutations on ATP1A3 protein function were investigated. Postmortem neuropathologic specimens from control and affected subjects were studied. Results: The mutations localized to the P domain of the Na, K-ATPase alpha 3 protein, and resulted in significant reduction of Na, K-ATPase activity in vitro. We demonstrate in both control human brain tissue and that from the subject with the p.Gly358Val mutation that ATP1A3 immunofluorescence is prominently associated with interneurons in the cortex, which may provide some insight into the pathogenesis of the disease. Significance: The findings indicate these mutations cause severe phenotypes of ATP1A3-related disorder spectrum that include catastrophic early life epilepsy, episodic apnea, and postnatal microcephaly. C1 [Paciorkowski, Alex R.] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA. [Paciorkowski, Alex R.] Univ Rochester, Med Ctr, Dept Pediat, Rochester, NY 14642 USA. [Paciorkowski, Alex R.] Univ Rochester, Med Ctr, Dept Biomed Genet, Rochester, NY 14642 USA. [Paciorkowski, Alex R.; Tuttle, Emily; Ghoneim, Dalia H.] Univ Rochester, Med Ctr, Ctr Neural Dev & Dis, Rochester, NY 14642 USA. [McDaniel, Sharon S.] Kaiser Permanente, Dept Pediat, San Francisco, CA USA. [Jansen, Laura A.; Tupal, Srinivasan; Gunter, Sonya A.] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Tully, Hannah] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Tully, Hannah; Vasta, Valeria; Zhang, Qing; Thao Tran; Hahn, Sihoun] Seattle Childrens Res Inst, Ctr Dev Therapeut, Seattle, WA USA. [Liu, Yi B.; Sweadner, Kathleen J.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Ozelius, Laurie J.] Icahn Sch Med Mt Sinai, Dept Genet, New York, NY 10029 USA. [Ozelius, Laurie J.] Icahn Sch Med Mt Sinai, Dept Genom Sci, New York, NY 10029 USA. [Ozelius, Laurie J.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Brashear, Allison] Wake Forest Sch Med, Dept Neurol, Winston Salem, NC USA. [Sweadner, Kathleen J.] Harvard Univ, Sch Med, Boston, MA USA. [Dobyns, William B.] Seattle Childrens Res Inst, Ctr Integrat Brain Res, Seattle, WA USA. [Dobyns, William B.; Hahn, Sihoun] Univ Washington, Dept Pediat, Div Med Genet, Seattle, WA 98195 USA. RP Paciorkowski, AR (reprint author), Univ Rochester, Med Ctr, Child Neurol, 601 Elmwood Ave, Rochester, NY 14642 USA. EM alex_paciorkowski@urmc.rochester.edu RI Brashear, Allison/G-3853-2015; OI Dobyns, William/0000-0002-7681-2844; Vasta, Valeria/0000-0002-8148-1795 FU National Institute of Neurologic Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) [K08NS078054, K02NS072162, R21NS081558, R01NS0 46616]; [LR11-328] FX The authors would like to thank the two children and their parents for participation in this study, and the parents of LR11-328 who provided funding for the studies of ATP1A3 activity. We also wish to acknowledge Dr. Raj Kapur, Seattle Children's Hospital, for his assistance with the clinical neuropathology data. Research reported in this work was supported by the National Institute of Neurologic Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) under award numbers K08NS078054 (A.R.P), K02NS072162 (L.A.J.), R21NS081558 (K.J.S.), and R01NS0 46616 (W.B.D.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 36 TC 16 Z9 16 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD MAR PY 2015 VL 56 IS 3 BP 422 EP 430 DI 10.1111/epi.12914 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CD6ZP UT WOS:000351240300014 PM 25656163 ER PT J AU Karamichos, D Zieske, JD Sejersen, H Sarker-Nag, A Asara, JM Hjortdal, J AF Karamichos, D. Zieske, J. D. Sejersen, H. Sarker-Nag, A. Asara, John M. Hjortdal, J. TI Tear metabolite changes in keratoconus SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE Keratoconus; Metabolomics; Oxidative stress; Rigid Gas Permeable lenses; Pentacam ID CONTACT-LENS WEAR; CORNEAL ALDEHYDE DEHYDROGENASE; OXIDATIVE STRESS; RECURRENT KERATOCONUS; PATHOLOGICAL CORNEAS; PROTEINS; GLUTATHIONE; THICKNESS; ACCUMULATION; EXPRESSION AB While efforts have been made over the years, the exact cause of keratoconus (KC) remains unknown. The aim of this study was to identify alterations in endogenous metabolites in the tears of KC patients compared with age-matched healthy subjects. Three groups were tested: 1) Age-matched controls with no eye disease (N = 15), 2) KC - patients wearing Rigid Gas permeable lenses (N = 16), and 3) KC - No Correction (N = 14). All samples were processed for metabolomics analysis using LC-MS/MS. We identified a total of 296 different metabolites of which >40 were significantly regulated between groups. Glycolysis and gluconeogenesis had significant changes, such as 3-phosphoglycerate and 1,3 diphosphateglycerate. As a result the citric acid cycle (TCA) was also affected with notable changes in Isocitrate, aconitate, malate, and acetylphosphate, up regulated in Group 2 and/or 3. Urea cycle was also affected, especially in Group 3 where ornithine and aspartate were up-regulated by at least 3 fold. The oxidation state was also severely affected. Groups 2 and 3 were under severe oxidative stress causing multiple metabolites to be regulated when compared to Group 1. Group 2 and 3, both showed significant down regulation in GSH-to-GSSG ratio when compared to Group 1. Another indicator of oxidative stress, the ratio of lactate - pyruvate was also affected with Groups 2 and 3 showing at least a 2-fold up regulation. Overall, our data indicate that levels of metabolites related to urea cycle, TCA cycle and oxidative stress are highly altered in KC patients. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Karamichos, D.; Sarker-Nag, A.] Univ Oklahoma, Dean McGee Eye Inst, Ophthalmol, Oklahoma City, OK 73104 USA. [Zieske, J. D.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [Zieske, J. D.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Sejersen, H.; Hjortdal, J.] Aarhus Univ Hosp, Dept Ophthalmol, DK-8000 Aarhus C, Denmark. [Asara, John M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Signal Transduct,Mass Spectrometry Core, Boston, MA 02215 USA. RP Karamichos, D (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, 608 Stanton L Young Blvd,DMEI PA-409, Oklahoma City, OK 73104 USA. EM dimitrios-karamichos@ouhsc.edu; james_zieske@meei.harvard.edu; henrseje@rm.dk; Akhee-SarkerNag@ouhsc.edu; jasara@bidmc.harvard.edu; jesper.hjortdal@dadlnet.dk RI karamichos, dimitrios/D-9651-2015 FU National Institutes of Health/National Eye Institute [5R01EY023568, 2P01CA120964]; Dana-Farber/Harvard Cancer Center Support Grant [5P30CA006516]; Research to Prevent Blindness, (New York, NY USA) FX The authors thank Min Yuan and Susanne Breitkopf for technical help with mass spectrometry experiments. The authors would also like to thank Dr. Robert E. Anderson for his input. This work was supported by National Institutes of Health/National Eye Institute Grant 5R01EY023568 (D.K), 2P01CA120964 (J.M.A.) and Dana-Farber/Harvard Cancer Center Support Grant 5P30CA006516 (J.M.A.). Also, supported, in part, by an unrestricted grant from Research to Prevent Blindness, (New York, NY USA). The Pentacam HR at Aarhus University Hospital was kindly donated by Bagenkop-Nielsens Myopia Foundation. NR 69 TC 6 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 EI 1096-0007 J9 EXP EYE RES JI Exp. Eye Res. PD MAR PY 2015 VL 132 BP 1 EP 8 DI 10.1016/j.exer.2015.01.007 PG 8 WC Ophthalmology SC Ophthalmology GA CD6HJ UT WOS:000351189900001 PM 25579606 ER PT J AU Parisi, LM Gabbay, RA AF Parisi, Laura M. Gabbay, Robert A. TI What Providers Want From the Primary Care Extension Service to Facilitate Practice Transformation SO FAMILY MEDICINE LA English DT Article ID CENTERED MEDICAL HOME; HEALTH; IMPROVEMENT AB BACKGROUND AND OBJECTIVES: While several experts have shared their visions of the Primary Care Extension Service (PCES) as called for in the Affordable Care Act (ACA), little is known about providers' perspective. We aimed to identify the most and least desired resources that primary care providers want from the PCES. METHODS: A 70-question survey was administered to primary care providers (n=556) in Pennsylvania, one of four initial states chosen to develop the PCES infrastructure. Analysis focused on the highest and lowest ranked questions. RESULTS: The most desired PCES services include (1) identifying and coordinating mental health services, (2) improving office efficiency, (3) increasing overall revenues, and (4) strategies to help implement evidence-based clinical guidelines. The least desired PCES services include (1) implementing e-prescribing, (2) implementing an electronic medical record (EMR) system, (3) implementing group visits, (4) recruiting new patients, and (5) implementing open or advanced access scheduling. CONCLUSIONS: Despite expert models presented for the PCES, there is a critical need to ask primary care providers what they need from such a service. Our findings identified some divergences from key patient-centered medical home (PCMH) components, including the low ranking of services related to EMRs and increasing patient access. With interest growing in developing a PCES that would help spread innovation as outlined in the ACA, it's important to take a demand-side approach to the services providers most desire versus the more traditional supply-side approach that assumes the assistance providers need. C1 [Parisi, Laura M.] Penn State Univ, Coll Med, University Pk, PA 16802 USA. [Gabbay, Robert A.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Cambridge, MA 02138 USA. RP Gabbay, RA (reprint author), Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02215 USA. EM gabbay@joslin.harvard.edu FU Agency for Healthcare Research and Quality [U18HS020988] FX This project was supported by grant number U18HS020988 from the Agency for Healthcare Research and Quality. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality NR 34 TC 0 Z9 0 U1 1 U2 2 PU SOC TEACHERS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, STE 540, LEAWOOD, KS 66207 USA SN 0742-3225 EI 1938-3800 J9 FAM MED JI Fam. Med. PD MAR PY 2015 VL 47 IS 3 BP 210 EP 216 PG 7 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA CD5HV UT WOS:000351119500007 PM 25853532 ER PT J AU Springelkamp, H Mishra, A Hysi, PG Gharahkhani, P Hohn, R Khor, CC Bailey, JNC Luo, XY Ramdas, WD Vithana, E Koh, V Yazar, S Xu, L Forward, H Kearns, LS Amin, N Iglesias, AI Sim, KS van Leeuwen, EM Demirkan, A van der Lee, S Loon, SC Rivadeneira, F Nag, A Sanfilippo, PG Schillert, A de Jong, PTVM Oostra, BA Uitterlinden, AG Hofman, A Zhou, T Burdon, KP Spector, TD Lackner, KJ Saw, SM Vingerling, JR Teo, YY Pasquale, LR Wolfs, RCW Lemij, HG Tai, ES Jonas, JB Cheng, CY Aung, T Jansonius, NM Klaver, CCW Craig, JE Young, TL Haines, JL MacGregor, S Mackey, DA Pfeiffer, N Wong, TY Wiggs, JL Hewitt, AW van Duijn, CM Hammond, CJ AF Springelkamp, Henriet Mishra, Aniket Hysi, Pirro G. Gharahkhani, Puya Hoehn, Rene Khor, Chiea-Chuen Bailey, Jessica N. Cooke Luo, Xiaoyan Ramdas, Wishal D. Vithana, Eranga Koh, Victor Yazar, Seyhan Xu, Liang Forward, Hannah Kearns, Lisa S. Amin, Najaf Iglesias, Adriana I. Sim, Kar-Seng van Leeuwen, Elisabeth M. Demirkan, Ayse van der Lee, Sven Loon, Seng-Chee Rivadeneira, Fernando Nag, Abhishek Sanfilippo, Paul G. Schillert, Arne de Jong, Paulus T. V. M. Oostra, Ben A. Uitterlinden, Andre G. Hofman, Albert Zhou, Tiger Burdon, Kathryn P. Spector, Timothy D. Lackner, Karl J. Saw, Seang-Mei Vingerling, Johannes R. Teo, Yik-Ying Pasquale, Louis R. Wolfs, Roger C. W. Lemij, Hans G. Tai, E-Shyong Jonas, Jost B. Cheng, Ching-Yu Aung, Tin Jansonius, Nomdo M. Klaver, Caroline C. W. Craig, Jamie E. Young, Terri L. Haines, Jonathan L. MacGregor, Stuart Mackey, David A. Pfeiffer, Norbert Wong, Tien-Yin Wiggs, Janey L. Hewitt, Alex W. van Duijn, Cornelia M. Hammond, Christopher J. CA NEIGHBORHOOD Consortium TI Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology SO GENETIC EPIDEMIOLOGY LA English DT Article DE GWAS; disc area; cup area; glaucoma ID OPEN-ANGLE GLAUCOMA; OCULAR-TISSUES; GENE; GENOTYPES; TRAITS; NERVE; ATOH7; SIZE AB Primary open-angle glaucoma is the most common optic neuropathy and an important cause of irreversible blindness worldwide. The optic nerve head or optic disc is divided in two parts: a central cup (without nerve fibers) surrounded by the neuroretinal rim (containing axons of the retinal ganglion cells). The International Glaucoma Genetics Consortium conducted a meta-analysis of genome-wide association studies consisting of 17,248 individuals of European ancestry and 6,841 individuals of Asian ancestry. The outcomes of the genome-wide association studies were disc area and cup area. These specific measurements describe optic nerve morphology in another way than the vertical cup-disc ratio, which is a clinically used measurement, and may shed light on new glaucoma mechanisms. We identified 10 new loci associated with disc area (CDC42BPA, F5, DIRC3, RARB, ABI3BP, DCAF4L2, ELP4, TMTC2, NR2F2, and HORMAD2) and another 10 new loci associated with cup area (DHRS3, TRIB2, EFEMP1, FLNB, FAM101, DDHD1, ASB7, KPNB1, BCAS3, and TRIOBP). The new genes participate in a number of pathways and future work is likely to identify more functions related to the pathogenesis of glaucoma. C1 [Springelkamp, Henriet; Amin, Najaf; Iglesias, Adriana I.; van Leeuwen, Elisabeth M.; Demirkan, Ayse; van der Lee, Sven; Rivadeneira, Fernando; Uitterlinden, Andre G.; Hofman, Albert; Klaver, Caroline C. W.; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Springelkamp, Henriet; Ramdas, Wishal D.; Wolfs, Roger C. W.; Klaver, Caroline C. W.] Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands. [Mishra, Aniket; Gharahkhani, Puya; MacGregor, Stuart] Royal Brisbane Hosp, QIMR Berghofer Med Res Inst, Stat Genet, Brisbane, Qld 4029, Australia. [Hysi, Pirro G.; Nag, Abhishek; Spector, Timothy D.; Hammond, Christopher J.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Hoehn, Rene; Pfeiffer, Norbert] Univ Med Ctr Mainz, Dept Ophthalmol, Mainz, Germany. [Hoehn, Rene; Lackner, Karl J.] Klin Pallas Olten, Olten, Switzerland. [Khor, Chiea-Chuen; Vithana, Eranga; Koh, Victor; Loon, Seng-Chee; Saw, Seang-Mei; Cheng, Ching-Yu; Aung, Tin; Wong, Tien-Yin] Natl Univ Singapore, Dept Ophthalmol, Singapore 117548, Singapore. [Khor, Chiea-Chuen; Vithana, Eranga; Koh, Victor; Loon, Seng-Chee; Saw, Seang-Mei; Cheng, Ching-Yu; Aung, Tin; Wong, Tien-Yin] Natl Univ Hlth Syst, Singapore, Singapore. [Khor, Chiea-Chuen; Sim, Kar-Seng] Genome Inst Singapore, Div Human Genet, Singapore, Singapore. [Bailey, Jessica N. Cooke; Haines, Jonathan L.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Luo, Xiaoyan; Young, Terri L.] Duke Univ, Ctr Eye, Durham, NC USA. [Vithana, Eranga; Saw, Seang-Mei; Cheng, Ching-Yu; Wong, Tien-Yin] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore. [Vithana, Eranga; Saw, Seang-Mei; Vingerling, Johannes R.; Cheng, Ching-Yu; Aung, Tin; Wong, Tien-Yin] Singapore Natl Eye Ctr, Eye Res Inst, Singapore, Singapore. [Yazar, Seyhan; Forward, Hannah; Sanfilippo, Paul G.; Mackey, David A.] Univ Western Australia, Ctr Ophthalmol & Visual Sci, Lions Eye Inst, Perth, WA 6009, Australia. [Xu, Liang] Capital Med Univ, Beijing Inst Ophthalmol, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing, Peoples R China. [Xu, Liang] Beijing Ophthalmol & Visual Sci Key Lab, Beijing, Peoples R China. [Kearns, Lisa S.; Sanfilippo, Paul G.; Hewitt, Alex W.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, CERA, Melbourne, Vic, Australia. [Demirkan, Ayse] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands. [Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Rivadeneira, Fernando; Uitterlinden, Andre G.; Hofman, Albert] Netherlands Genom Initiat, Netherlands Consortium Hlth Ageing, The Hague, Netherlands. [Schillert, Arne] Partner Site Hamburg Kiel Lubeck, DZHK German Ctr Cardiovasc Res, Lubeck, Germany. [Schillert, Arne] Med Univ Lubeck, Inst Med Biometry & Stat, D-23538 Lubeck, Germany. [de Jong, Paulus T. V. M.] Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, NL-1105 AZ Amsterdam, Netherlands. [de Jong, Paulus T. V. M.] Leiden Univ, Med Ctr, Dept Ophthalmol, Leiden, Netherlands. [de Jong, Paulus T. V. M.] Netherlands Inst Neurosci, Dept Retinal Signal Proc, Amsterdam, Netherlands. [Oostra, Ben A.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. [Zhou, Tiger; Craig, Jamie E.] Flinders Univ S Australia, Dept Ophthalmol, Adelaide, SA 5001, Australia. [Burdon, Kathryn P.; Mackey, David A.; Hewitt, Alex W.] Univ Tasmania, Menzies Res Inst Tasmania, Sch Med, Hobart, Tas, Australia. [Saw, Seang-Mei; Teo, Yik-Ying; Tai, E-Shyong] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore. [Saw, Seang-Mei; Teo, Yik-Ying; Tai, E-Shyong] Natl Univ Hlth Syst, Singapore, Singapore. [Teo, Yik-Ying; Tai, E-Shyong] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore. [Pasquale, Louis R.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Pasquale, Louis R.; Wiggs, Janey L.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Pasquale, Louis R.; Wiggs, Janey L.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Lemij, Hans G.] Rotterdam Eye Hosp, Glaucoma Serv, Rotterdam, Netherlands. [Tai, E-Shyong] Natl Univ Singapore, Dept Med, Singapore 117548, Singapore. [Tai, E-Shyong] Natl Univ Hlth Syst, Singapore, Singapore. [Jonas, Jost B.] Heidelberg Univ, Dept Ophthalmol, Med Fac Mannheim, Heidelberg, Germany. [Jansonius, Nomdo M.] Univ Groningen, Univ Med Ctr Groningen, Dept Ophthalmol, Groningen, Netherlands. RP Springelkamp, H (reprint author), Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. EM c.vanduijn@erasmusmc.nl RI Macgregor, Stuart/C-6442-2009; Hewitt, Alex/D-1936-2013; Mackey, David/H-5340-2014; OI Macgregor, Stuart/0000-0001-6731-8142; Hewitt, Alex/0000-0002-5123-5999; Mackey, David/0000-0001-7914-4709; Sim, Kar Seng/0000-0002-3822-7759; Yazar, Seyhan/0000-0003-0994-6196; Gharahkhani, Puya/0000-0002-4203-5952; Hohn, Rene /0000-0003-2870-1469; Tai, E Shyong/0000-0003-2929-8966; Rivadeneira, Fernando/0000-0001-9435-9441; Khor, Chiea Chuen/0000-0002-1128-4729; Hammond, Christopher/0000-0002-3227-2620 FU Department of Health [SRF/01/010]; NEI NIH HHS [R01 EY011405, R01 EY013178, R01 EY015473, R01 EY022305, P30 EY014104, R01 EY004859, R01 EY023754] NR 25 TC 14 Z9 14 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD MAR PY 2015 VL 39 IS 3 BP 207 EP 216 DI 10.1002/gepi.21886 PG 10 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA CD9ZW UT WOS:000351462200008 PM 25631615 ER PT J AU Clark, RM Lee, MS Rauh-Hain, JA Hall, T Boruta, DM del Carmen, MG Goodman, A Schorge, JO Growdon, WB AF Clark, Rachel M. Lee, Malinda S. Rauh-Hain, J. Alejandro Hall, Tracilyn Boruta, David M. del Carmen, Marcela G. Goodman, Annekathryn Schorge, John O. Growdon, Whitfield B. TI Surgical Apgar Score and prediction of morbidity in women undergoing hysterectomy for malignancy SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Surgical Apgar Score; Hysterectomy; Morbidity; Complications; Gynecologic oncology ID EPITHELIAL OVARIAN-CARCINOMA; HOSPITAL READMISSION; VALIDATION; SURGERY; CARE; CYTOREDUCTION; POPULATION; ADMISSION; OUTCOMES; PATIENT AB Objective. To validate whether Surgical Apgar Score can predict post-operative morbidity in patients undergoing hysterectomies for malignancies. Methods. We conducted a retrospective cohort study of consecutive hysterectomies performed for cancer at a single academic institution between 2008 and 2010. The Surgical Apgar Score (SAS) was derived as previously reported. Pen-operative complications were as outlined by the American Board for Obstetrics and Gynecology, and then further subdivided into intra-operative and post-operative events. Univariate and multivariate logistic regressions were utilized. Results. A total of 632 patients were identified. Of our cohort, 64% underwent surgery for cancer arising in the uterus, followed by ovary at 28.6% and cervix at 4%. Median patient age was 60 years old with a mean American Society of Anesthesiologists Physical Status Classification System (ASA) score of 2.5 and a median body mass index of 29. Average Surgical Apgar Score was 7.6. As SAS decreased, the risk of pen-operative complications increased (p < 0.01). On univariate analysis SAS could predict for both intra-operative and postoperative complications. However, on multivariate analyses SAS could not independently predict for any post-operative complications (OR 1.02, CI 0.47-2.17). In a multivariable model incorporating age, ASA class, SAS <4, disease site, bowel resection and laparotomy, only ASA class and laparotomy were able to predict for postoperative complication events. Conclusions. Low Surgical Apgar Score significantly associates with morbidity in women undergoing hysterectomy for malignancy, but is unable to predict which patients will have postoperative complications. This renders the SAS less helpful for the creation of pen-operative metrics to guide post-operative care. (C) 2014 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Clark, RM (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM rmclark@partners.org NR 30 TC 4 Z9 5 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2015 VL 136 IS 3 BP 516 EP 520 DI 10.1016/j.ygyno.2014.11.016 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CD6GJ UT WOS:000351187300016 PM 25475542 ER PT J AU Schorge, JO AF Schorge, John O. TI y Cocytus: Have you begun your descent? SO GYNECOLOGIC ONCOLOGY LA English DT Review DE Mentoring; Professional development; Academic career ID PROCRASTINATION; SURGERY AB The vast majority of trainees entering a fellowship express a sincere interest in pursuing an 'academic career'. However, even the most dedicated souls will find their own path toward that worthy goal fraught with a number of unanticipated hazards-any one of which could result in a fullstop of professional advancement. Of interest, many of the obstacles are actually self-imposed, usually buried within the subconscious self. Without guidance of how to recognize and address these shortcomings, abandonment of one's original career trajectory may be seriously considered, and often acted upon. By the time any one of us has completed training, taken the boards, and gotten to this inflection point, we are at least in our mid- to late-30s. What then, is there to do, about this looming phenomenon, whenever it may occur? Perhaps we can draw comfort from a historical figure who has been there, and done that. His journey embodies the value of mentoring in traversing the succession of personal perils that are commonplace in today's professional environment (C) 2015 Elsevier Inc. All rights reserved. C1 [Schorge, John O.] Massachusetts Gen Hosp, Vincent Gynecol Oncol Serv, Boston, MA 02114 USA. RP Schorge, JO (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Gynecol Oncol Serv, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM jschorge@partners.org NR 12 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2015 VL 136 IS 3 BP 582 EP 588 DI 10.1016/j.ygyno.2014.12.040 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CD6GJ UT WOS:000351187300026 PM 25575482 ER PT J AU Coutinho, R Clear, AJ Mazzola, E Owen, A Greaves, P Wilson, A Matthews, J Lee, A Alvarez, R da Silva, MG Cabecadas, J Neuberg, D Calaminici, M Gribben, JG AF Coutinho, Rita Clear, Andrew J. Mazzola, Emanuele Owen, Andrew Greaves, Paul Wilson, Andrew Matthews, Janet Lee, Abigail Alvarez, Rute da Silva, Maria Gomes Cabecadas, Jose Neuberg, Donna Calaminici, Maria Gribben, John G. TI Revisiting the immune microenvironment of diffuse large B-cell lymphoma using a tissue microarray and immunohistochemistry: robust semi- automated analysis reveals CD3 and FoxP3 as potential predictors of response to R-CHOP SO HAEMATOLOGICA LA English DT Article ID REGULATORY T-CELLS; TUMOR-ASSOCIATED MACROPHAGES; FOLLICULAR LYMPHOMA; HODGKINS-LYMPHOMA; BIOMARKER CONSORTIUM; RITUXIMAB; SURVIVAL; CHEMOTHERAPY; EXPRESSION; VALIDATION AB Gene expression studies have identified the microenvironment as a prognostic player in diffuse large B- cell lymphoma. However, there is a lack of simple immune biomarkers that can be applied in the clinical setting and could be helpful in stratifying patients. Immunohistochemistry has been used for this purpose but the results are inconsistent. We decided to reinvestigate the immune microenvironment and its impact using immunohistochemistry, with two systems of image analysis, in a large set of patients with diffuse large B- cell lymphoma. Diagnostic tissue from 309 patients was arrayed onto tissue microarrays. Results from 161 chemoimmunotherapy- treated patients were used for outcome prediction. Positive cells, percentage stained area and numbers of pixels/ area were quantified and results were compared with the purpose of inferring consistency between the two semi- automated systems. Measurement cutpoints were assessed using a recursive partitioning algorithm classifying results according to survival. Kaplan- Meier estimators and Fisher exact tests were evaluated to check for significant differences between measurement classes, and for dependence between pairs of measurements, respectively. Results were validated by multivariate analysis incorporating the International Prognostic Index. The concordance between the two systems of image analysis was surprisingly high, supporting their applicability for immunohistochemistry studies. Patients with a high density of CD3 and FoxP3 by both methods had a better outcome. Automated analysis should be the preferred method for immunohistochemistry studies. Following the use of two methods of semi- automated analysis we suggest that CD3 and FoxP3 play a role in predicting response to chemoimmunotherapy in diffuse large B- cell lymphoma. C1 [Coutinho, Rita; Clear, Andrew J.; Owen, Andrew; Greaves, Paul; Wilson, Andrew; Matthews, Janet; Lee, Abigail; Calaminici, Maria; Gribben, John G.] Queen Mary Univ, Barts Canc Inst, Dept Hematooncol, London, England. [Mazzola, Emanuele] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Owen, Andrew; Lee, Abigail; Neuberg, Donna; Calaminici, Maria] Barts Hlth NHS Trust, Royal London Hosp, Dept Histopathol, London, England. [Alvarez, Rute; da Silva, Maria Gomes] Portuguese Inst Oncol, Dept Hematol, Lisbon, Portugal. [Cabecadas, Jose] Portuguese Inst Oncol, Dept Pathol, Lisbon, Portugal. RP Coutinho, R (reprint author), Queen Mary Univ, Barts Canc Inst, Dept Hematooncol, London, England. EM rittakoutinho@gmail.com OI Greaves, Paul/0000-0002-3318-7233; Cabecadas, Jose/0000-0001-6232-1596; Gomes da Silva, Maria/0000-0002-6993-2450 FU NCI NIH HHS [P01 CA081534, P01 CA81538]; PHS HHS [C1574/A6806] NR 27 TC 8 Z9 8 U1 1 U2 9 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD MAR PY 2015 VL 100 IS 3 BP 363 EP 369 DI 10.3324/haematol.2014.110189 PG 7 WC Hematology SC Hematology GA CD7OK UT WOS:000351279900026 PM 25425693 ER PT J AU Evins, AE Cather, C Laffer, A AF Evins, A. Eden Cather, Corinne Laffer, Alexandra TI Treatment of Tobacco Use Disorders in Smokers with Serious Mental Illness: Toward Clinical Best Practices SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE bipolar; depression; nicotine use disorder; randomized controlled trial; schizophrenia; severe mental illness; smoking cessation; tobacco use ID PLACEBO-CONTROLLED TRIAL; SMOKING-CESSATION INTERVENTIONS; BIPOLAR DISORDER; CIGARETTE-SMOKING; MAJOR DEPRESSION; DOUBLE-BLIND; UNITED-STATES; SCHIZOAFFECTIVE DISORDER; SCHIZOPHRENIC SMOKERS; NICOTINE DEPENDENCE AB Addiction to tobacco-derived nicotine remains highly prevalent in the United States, with 18% using daily, and 53% of those with serious mental illness using daily. While smokers with serious mental illness have been excluded from most large nicotine-dependence treatment studies, a growing evidence base is available to guide clinicians in assisting their patients with psychiatric illness to quit smoking. The aim of this review is to present the evidence on safety and efficacy of smoking cessation interventions for those with serious mental illness. Smokers with schizophrenia spectrum disorders should receive varenicline or bupropion with or without nicotine replacement therapy in combination with behavioral treatment. Although more research is needed, preliminary evidence suggests that varenicline in combination with behavioral support is efficacious and well tolerated for smoking cessation for those with bipolar disorder and major depressive disorder. Controlled trials have found no evidence that in patients with serious mental illness, the use of pharmacotherapeutic cessation aids worsens psychiatric symptoms or increases the rate of psychiatric adverse events. Converging evidence indicates that a majority of smokers with serious mental illness want to quit smoking and that available pharmacotherapeutic cessation aids combined with behavioral support are both effective for, and well tolerated by, these smokers. C1 [Evins, A. Eden; Cather, Corinne] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Evins, A. Eden; Cather, Corinne; Laffer, Alexandra] Massachusetts Gen Hosp, Ctr Addict Med, Dept Psychiat, Boston, MA 02114 USA. RP Cather, C (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC812, Boston, MA 02114 USA. EM ccather@mgh.harvard.edu FU National Institute on Drug Abuse [R01 DA021245, K24 DA030443] FX National Institute on Drug Abuse grant nos. R01 DA021245 and K24 DA030443 (Dr. Evins). NR 77 TC 13 Z9 13 U1 2 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1067-3229 EI 1465-7309 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2015 VL 23 IS 2 BP 90 EP 98 DI 10.1097/HRP.0000000000000063 PG 9 WC Psychiatry SC Psychiatry GA CD9TQ UT WOS:000351441700004 PM 25747922 ER PT J AU Sivashanker, K Mufson, M Mittal, L Ross, E Suzuki, J AF Sivashanker, Karthik Mufson, Michael Mittal, Leena Ross, Edgar Suzuki, Joji TI Challenges in Managing Acute on Chronic Pain in a Pregnant Woman at High Risk for Opioid Use Disorder in the General Hospital Setting SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE addiction; consultation-liaison psychiatry; dependence; opiate; opioid; pain; pregnancy; psychosomatic; substance abuse ID NEONATAL ABSTINENCE SYNDROME; CHRONIC NONMALIGNANT PAIN; DEPENDENT PATIENTS; BREAST-MILK; BUPRENORPHINE; MANAGEMENT; METHADONE; WOMEN; EXPOSURE; THERAPY C1 [Sivashanker, Karthik] VA Boston Healthcare Syst, Dept Psychiat, Jamaica Plain, MA 02130 USA. [Mufson, Michael; Mittal, Leena; Ross, Edgar; Suzuki, Joji] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Mittal, Leena; Suzuki, Joji] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Ross, Edgar] Brigham & Womens Hosp, Pain Management Ctr, Boston, MA 02115 USA. RP Sivashanker, K (reprint author), VA Boston Healthcare Syst, Dept Psychiat, 251 Heath St,201, Jamaica Plain, MA 02130 USA. EM sivashanker@gmail.com NR 61 TC 0 Z9 0 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1067-3229 EI 1465-7309 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2015 VL 23 IS 2 BP 157 EP 166 DI 10.1097/HRP.0000000000000080 PG 10 WC Psychiatry SC Psychiatry GA CD9TQ UT WOS:000351441700010 PM 25747928 ER EF